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Sample records for backbone structure variations

  1. External Tank - The Structure Backbone

    NASA Technical Reports Server (NTRS)

    Welzyn, Kenneth; Pilet, Jeffrey C.; Diecidue-Conners, Dawn; Worden, Michelle; Guillot, Michelle

    2011-01-01

    The External Tank forms the structural backbone of the Space Shuttle in the launch configuration. Because the tank flies to orbital velocity with the Space Shuttle Orbiter, minimization of weight is mandatory, to maximize payload performance. Choice of lightweight materials both for structure and thermal conditioning was necessary. The tank is large, and unique manufacturing facilities, tooling, handling, and transportation operations were required. Weld processes and tooling evolved with the design as it matured through several block changes, to reduce weight. Non Destructive Evaluation methods were used to assure integrity of welds and thermal protection system materials. The aluminum-lithium alloy was used near the end of the program and weld processes and weld repair techniques had to be refined. Development and implementation of friction stir welding was a substantial technology development incorporated during the Program. Automated thermal protection system application processes were developed for the majority of the tank surface. Material obsolescence was an issue throughout the 40 year program. The final configuration and tank weight enabled international space station assembly in a high inclination orbit allowing international cooperation with the Russian Federal Space Agency. Numerous process controls were implemented to assure product quality, and innovative proof testing was accomplished prior to delivery. Process controls were implemented to assure cleanliness in the production environment, to control contaminants, and to preclude corrosion. Each tank was accepted via rigorous inspections, including non-destructive evaluation techniques, proof testing, and all systems testing. In the post STS-107 era, the project focused on ascent debris risk reduction. This was accomplished via stringent process controls, post flight assessment using substantially improved imagery, and selective redesigns. These efforts were supported with a number of test programs to

  2. Solution Structure and Backbone Dynamics of Streptopain

    PubMed Central

    Wang, Chih-Chieh; Houng, Hsiang-Chee; Chen, Chun-Liang; Wang, Pei-Ju; Kuo, Chih-Feng; Lin, Yee-Shin; Wu, Jiunn-Jong; Lin, Ming T.; Liu, Ching-Chuan; Huang, Wenya; Chuang, Woei-Jer

    2009-01-01

    Streptococcal pyrogenic exotoxin B (SPE B) is a cysteine protease expressed by Streptococcus pyogenes. The D9N, G163S, G163S/A172S, and G239D mutant proteins were expressed to study the effect of the allelic variants on their protease activity. In contrast to other mutants, the G239D mutant was ∼12-fold less active. The Gly-239 residue is located within the C-terminal S230-G239 region, which cannot be observed in the x-ray structure. The three-dimensional structure and backbone dynamics of the 28-kDa mature SPE B (mSPE B) were determined. Unlike the x-ray structure of the 40-kDa zymogen SPE B (proSPE B), we observed the interactions between the C-terminal loop and the active site residues in mSPE B. The structural differences between mSPE B and proSPE B were the conformation of the C-terminal loop and the orientation of the catalytic His-195 residue, suggesting that activation and inactivation of SPE B is involved in the His-195 side-chain rotation. Dynamics analysis of mSPE B and the mSPE B/inhibitor complexes showed that the catalytic and C-terminal loops were the most flexible regions with low order parameter values of 0.5 to 0.8 and exhibited the motion on the ps/ns timescale. These findings suggest that the flexible C-terminal loop of SPE B may play an important role in controlling the substrate binding, resulting in its broad substrate specificity. PMID:19237546

  3. Local backbone structure prediction of proteins.

    PubMed

    de Brevern, Alexandre G; Benros, Cristina; Gautier, Romain; Valadié, Héléne; Hazout, Serge; Etchebest, Catherine

    2004-01-01

    A statistical analysis of the PDB structures has led us to define a new set of small 3D structural prototypes called Protein Blocks (PBs). This structural alphabet includes 16 PBs, each one is defined by the (phi, psi) dihedral angles of 5 consecutive residues. The amino acid distributions observed in sequence windows encompassing these PBs are used to predict by a Bayesian approach the local 3D structure of proteins from the sole knowledge of their sequences. LocPred is a software which allows the users to submit a protein sequence and performs a prediction in terms of PBs. The prediction results are given both textually and graphically. PMID:15724288

  4. A New Secondary Structure Assignment Algorithm Using Cα Backbone Fragments.

    PubMed

    Cao, Chen; Wang, Guishen; Liu, An; Xu, Shutan; Wang, Lincong; Zou, Shuxue

    2016-01-01

    The assignment of secondary structure elements in proteins is a key step in the analysis of their structures and functions. We have developed an algorithm, SACF (secondary structure assignment based on Cα fragments), for secondary structure element (SSE) assignment based on the alignment of Cα backbone fragments with central poses derived by clustering known SSE fragments. The assignment algorithm consists of three steps: First, the outlier fragments on known SSEs are detected. Next, the remaining fragments are clustered to obtain the central fragments for each cluster. Finally, the central fragments are used as a template to make assignments. Following a large-scale comparison of 11 secondary structure assignment methods, SACF, KAKSI and PROSS are found to have similar agreement with DSSP, while PCASSO agrees with DSSP best. SACF and PCASSO show preference to reducing residues in N and C cap regions, whereas KAKSI, P-SEA and SEGNO tend to add residues to the terminals when DSSP assignment is taken as standard. Moreover, our algorithm is able to assign subtle helices (310-helix, π-helix and left-handed helix) and make uniform assignments, as well as to detect rare SSEs in β-sheets or long helices as outlier fragments from other programs. The structural uniformity should be useful for protein structure classification and prediction, while outlier fragments underlie the structure-function relationship. PMID:26978354

  5. A New Secondary Structure Assignment Algorithm Using Cα Backbone Fragments

    PubMed Central

    Cao, Chen; Wang, Guishen; Liu, An; Xu, Shutan; Wang, Lincong; Zou, Shuxue

    2016-01-01

    The assignment of secondary structure elements in proteins is a key step in the analysis of their structures and functions. We have developed an algorithm, SACF (secondary structure assignment based on Cα fragments), for secondary structure element (SSE) assignment based on the alignment of Cα backbone fragments with central poses derived by clustering known SSE fragments. The assignment algorithm consists of three steps: First, the outlier fragments on known SSEs are detected. Next, the remaining fragments are clustered to obtain the central fragments for each cluster. Finally, the central fragments are used as a template to make assignments. Following a large-scale comparison of 11 secondary structure assignment methods, SACF, KAKSI and PROSS are found to have similar agreement with DSSP, while PCASSO agrees with DSSP best. SACF and PCASSO show preference to reducing residues in N and C cap regions, whereas KAKSI, P-SEA and SEGNO tend to add residues to the terminals when DSSP assignment is taken as standard. Moreover, our algorithm is able to assign subtle helices (310-helix, π-helix and left-handed helix) and make uniform assignments, as well as to detect rare SSEs in β-sheets or long helices as outlier fragments from other programs. The structural uniformity should be useful for protein structure classification and prediction, while outlier fragments underlie the structure–function relationship. PMID:26978354

  6. Backbone Solution Structures of Proteins Using Residual Dipolar Couplings: Application to a Novel Structural Genomics Target

    PubMed Central

    Valafar, H.; Mayer, K. L.; Bougault, C. M.; LeBlond, P. D.; Jenney, F. E.; Brereton, P. S.; Adams, M.W.W.; Prestegard, J.H.

    2006-01-01

    Structural genomics (or proteomics) activities are critically dependent on the availability of high-throughput structure determination methodology. Development of such methodology has been a particular challenge for NMR based structure determination because of the demands for isotopic labeling of proteins and the requirements for very long data acquisition times. We present here a methodology that gains efficiency from a focus on determination of backbone structures of proteins as opposed to full structures with all side chains in place. This focus is appropriate given the presumption that many protein structures in the future will be built using computational methods that start from representative fold family structures and replace as many as 70% of the side chains in the course of structure determination. The methodology we present is based primarily on residual dipolar couplings (RDCs), readily accessible NMR observables that constrain the orientation of backbone fragments irrespective of separation in space. A new software tool is described for the assembly of backbone fragments under RDC constraints and an application to a structural genomics target is presented. The target is an 8.7 kDa protein from Pyrococcus furiosus, PF1061, that was previously not well annotated, and had a nearest structurally characterized neighbor with only 33% sequence identity. The structure produced shows structural similarity to this sequence homologue, but also shows similarity to other proteins that suggests a functional role in sulfur transfer. Given the backbone structure and a possible functional link this should be an ideal target for development of modeling methods. PMID:15704012

  7. Changing the topology of protein backbone: the effect of backbone cyclization on the structure and dynamics of a SH3 domain

    PubMed Central

    Schumann, Frank H.; Varadan, Ranjani; Tayakuniyil, Praveen P.; Grossman, Jennifer H.; Camarero, Julio A.; Fushman, David

    2015-01-01

    Understanding of the effects of the backbone cyclization on the structure and dynamics of a protein is essential for using protein topology engineering to alter protein stability and function. Here we have determined, for the first time, the structure and dynamics of the linear and various circular constructs of the N-SH3 domain from protein c-Crk. These constructs differ in the length and amino acid composition of the cyclization region. The backbone cyclization was carried out using intein-mediated intramolecular chemical ligation between the juxtaposed N- and the C-termini. The structure and backbone dynamics studies were performed using solution NMR. Our data suggest that the backbone cyclization has little effect on the overall three-dimensional structure of the SH3 domain: besides the termini, only minor structural changes were found in the proximity of the cyclization region. In contrast to the structure, backbone dynamics are significantly affected by the cyclization. On the subnanosecond time scale, the backbone of all circular constructs on average appears more rigid than that of the linear SH3 domain; this effect is observed over the entire backbone and is not limited to the cyclization site. The backbone mobility of the circular constructs becomes less restricted with increasing length of the circularization loop. In addition, significant conformational exchange motions (on the sub-millisecond time scale) were found in the N-Src loop and in the adjacent β-strands in all circular constructs studied in this work. These effects of backbone cyclization on protein dynamics have potential implications for the stability of the protein fold and for ligand binding. PMID:25905098

  8. Automated Real-Space Refinement of Protein Structures Using a Realistic Backbone Move Set

    PubMed Central

    Haddadian, Esmael J.; Gong, Haipeng; Jha, Abhishek K.; Yang, Xiaojing; DeBartolo, Joe; Hinshaw, James R.; Rice, Phoebe A.; Sosnick, Tobin R.; Freed, Karl F.

    2011-01-01

    Crystals of many important biological macromolecules diffract to limited resolution, rendering accurate model building and refinement difficult and time-consuming. We present a torsional optimization protocol that is applicable to many such situations and combines Protein Data Bank-based torsional optimization with real-space refinement against the electron density derived from crystallography or cryo-electron microscopy. Our method converts moderate- to low-resolution structures at initial (e.g., backbone trace only) or late stages of refinement to structures with increased numbers of hydrogen bonds, improved crystallographic R-factors, and superior backbone geometry. This automated method is applicable to DNA-binding and membrane proteins of any size and will aid studies of structural biology by improving model quality and saving considerable effort. The method can be extended to improve NMR and other structures. Our backbone score and its sequence profile provide an additional standard tool for evaluating structural quality. PMID:21843481

  9. Structurally diverse cyclisation linkers impose different backbone conformations in bicyclic peptides.

    PubMed

    Chen, Shiyu; Morales-Sanfrutos, Julia; Angelini, Alessandro; Cutting, Brian; Heinis, Christian

    2012-05-01

    Combinatorial libraries of structurally diverse peptide macrocycles offer a rich source for the development of high-affinity ligands to targets of interest. In this work we have developed linkers for the generation of genetically encoded bicyclic peptides and tested whether the peptides cyclised by them have significant variations in their backbone conformations. Two new cyclisation reagents, each containing three thiol-reactive groups, efficiently and selectively cyclised linear peptides containing three cysteine moieties. When the mesitylene linker of the bicyclic peptide PK15, a potent inhibitor of plasma kallikrein (K(i)=2 nM), was replaced by the new linkers, its inhibitory activity dropped by a factor of more than 1000, suggesting that the linkers impose different conformations on the peptide. Indeed, structural analysis by solution-state NMR revealed different NOE constraints in the three bicyclic peptides, indicating that these relatively small linkers at the centres of bicyclic peptide structures significantly influence the conformations of the peptides. These results demonstrate the prominent structural role of linkers in peptide macrocycles and suggest that application of different cyclisation linkers in a combinatorial fashion could be an attractive means to generate topologically diverse macrocycle libraries. PMID:22492661

  10. Lasso peptide, a highly stable structure and designable multifunctional backbone.

    PubMed

    Zhao, Ning; Pan, Yongxu; Cheng, Zhen; Liu, Hongguang

    2016-06-01

    Lasso peptide belongs to a new class of natural product with highly compact and stable structure. It has varieties of biological activities, among which the most important one is its antibacterial efficacy. Novel lasso peptides have been constantly discovered and analyzed by advanced techniques, and the biosynthesis or even chemical synthesis of lasso peptide has been studied after learning its constituent amino acids and maturation process. Structural identification of lasso peptide provides information for elucidating the mechanisms of its antibacterial activity and basis for further modifications. Ring of lasso peptide is the key to both its highly compact and stable structure and its intrinsic antibacterial property. The loop has been considered as suitable modification region of lasso peptide, such as V11-S18 of MccJ25 being modifiable without disrupting the lasso structure in biosynthesis. The tail is the immunity protein that can export lasso peptide out of its produced strain and serve as a self-protection mechanism at the same time. Most of currently known lasso peptides are non-pathogenic, which implies that the modified lasso peptides are promising candidates for medical applications. Arginine, glycine, and aspartic acid as a ligands of cancer-specific receptor have been grafted to the loop of lasso peptide without losing its bioactivity, and many other targets are expected to be used for lasso peptide modification. Multi-molecular modification and large-scale production need to be studied and solved in future for designing and using multifunctional lasso peptide based on its extraordinary stable structure. PMID:27074719

  11. A structural role for arginine in proteins: multiple hydrogen bonds to backbone carbonyl oxygens.

    PubMed

    Borders, C L; Broadwater, J A; Bekeny, P A; Salmon, J E; Lee, A S; Eldridge, A M; Pett, V B

    1994-04-01

    We propose that arginine side chains often play a previously unappreciated general structural role in the maintenance of tertiary structure in proteins, wherein the positively charged guanidinium group forms multiple hydrogen bonds to backbone carbonyl oxygens. Using as a criterion for a "structural" arginine one that forms 4 or more hydrogen bonds to 3 or more backbone carbonyl oxygens, we have used molecular graphics to locate arginines of interest in 4 proteins: Arg 180 in Thermus thermophilus manganese superoxide dismutase, Arg 254 in human carbonic anhydrase II, Arg 31 in Streptomyces rubiginosus xylose isomerase, and Arg 313 in Rhodospirillum rubrum ribulose-1,5-bisphosphate carboxylase/oxygenase. Arg 180 helps to mold the active site channel of superoxide dismutase, whereas in each of the other enzymes the structural arginine is buried in the "mantle" (i.e., inside, but near the surface) of the protein interior well removed from the active site, where it makes 5 hydrogen bonds to 4 backbone carbonyl oxygens. Using a more relaxed criterion of 3 or more hydrogen bonds to 2 or more backbone carbonyl oxygens, arginines that play a potentially important structural role were found in yeast enolase, Bacillus stearothermophilus glyceraldehyde-3-phosphate dehydrogenase, bacteriophage T4 and human lysozymes, Enteromorpha prolifera plastocyanin, HIV-1 protease, Trypanosoma brucei brucei and yeast triosephosphate isomerases, and Escherichia coli trp aporepressor (but not trp repressor or the trp repressor/operator complex).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8003972

  12. East vergent structure of Backbone Range: Insights from A-Lan-Yi area and sandbox modeling

    NASA Astrophysics Data System (ADS)

    Lee, C. A.; Lu, C. Y.

    2015-12-01

    Southern Taiwan, including Pingtung peninsula and Taitung, is the incipient oblique collision zone of Eurasian plate and Philippine Sea plate. The Luzon volcanic arc converged toward Taiwan Island and formed Hengchun Ridge south offshore Taiwan. Thus, Taiwan mountain belt developed from north to south as the Backbone Range, so that we can infer the incipient feature structure from the topography and outcrop study of southern Taiwan. Our field survey of this study concentrated at the southeast coastline of Taiwan, also known as A-Lan-Yi Trail. According to previous study, the deformational structures such as faults and folds are consistent with regional kinematic processes, and the preserved transpression structure is the most important evidence of incipient collision. In this study, we use the sedimentary sequences of study area to trace the regional tectonics from north to south. Discovered structures in this area show the similar kinematic history as the eastern flank of Backbone Range, so that we suggest they are at the same series of a tectonic event. To complete the regional structure mapping in this accessible area, besides the field geological data, we also applied the LiDAR-derived DTM which is a 3D visualization technology to improve our topography information. In addition, we use the sandbox modeling to demonstrate the development of structures in the eastern flank of Backbone Range. After combining the results of field observation and regional structure mapping, this study provides a strong evidence of backthrusting and backfolding deformation during the incipient oblique collision stage.

  13. On the satisfaction of backbone-carbonyl lone pairs of electrons in protein structures.

    PubMed

    Bartlett, Gail J; Woolfson, Derek N

    2016-04-01

    Protein structures are stabilized by a variety of noncovalent interactions (NCIs), including the hydrophobic effect, hydrogen bonds, electrostatic forces and van der Waals' interactions. Our knowledge of the contributions of NCIs, and the interplay between them remains incomplete. This has implications for computational modeling of NCIs, and our ability to understand and predict protein structure, stability, and function. One consideration is the satisfaction of the full potential for NCIs made by backbone atoms. Most commonly, backbone-carbonyl oxygen atoms located within α-helices and β-sheets are depicted as making a single hydrogen bond. However, there are two lone pairs of electrons to be satisfied for each of these atoms. To explore this, we used operational geometric definitions to generate an inventory of NCIs for backbone-carbonyl oxygen atoms from a set of high-resolution protein structures and associated molecular-dynamics simulations in water. We included more-recently appreciated, but weaker NCIs in our analysis, such as n→π* interactions, Cα-H bonds and methyl-H bonds. The data demonstrate balanced, dynamic systems for all proteins, with most backbone-carbonyl oxygen atoms being satisfied by two NCIs most of the time. Combinations of NCIs made may correlate with secondary structure type, though in subtly different ways from traditional models of α- and β-structure. In addition, we find examples of under- and over-satisfied carbonyl-oxygen atoms, and we identify both sequence-dependent and sequence-independent secondary-structural motifs in which these reside. Our analysis provides a more-detailed understanding of these contributors to protein structure and stability, which will be of use in protein modeling, engineering and design. PMID:26833776

  14. Toward Atomistic Resolution Structure of Phosphatidylcholine Headgroup and Glycerol Backbone at Different Ambient Conditions.

    PubMed

    Botan, Alexandru; Favela-Rosales, Fernando; Fuchs, Patrick F J; Javanainen, Matti; Kanduč, Matej; Kulig, Waldemar; Lamberg, Antti; Loison, Claire; Lyubartsev, Alexander; Miettinen, Markus S; Monticelli, Luca; Määttä, Jukka; Ollila, O H Samuli; Retegan, Marius; Róg, Tomasz; Santuz, Hubert; Tynkkynen, Joona

    2015-12-10

    Phospholipids are essential building blocks of biological membranes. Despite a vast amount of very accurate experimental data, the atomistic resolution structures sampled by the glycerol backbone and choline headgroup in phoshatidylcholine bilayers are not known. Atomistic resolution molecular dynamics simulations have the potential to resolve the structures, and to give an arrestingly intuitive interpretation of the experimental data, but only if the simulations reproduce the data within experimental accuracy. In the present work, we simulated phosphatidylcholine (PC) lipid bilayers with 13 different atomistic models, and compared simulations with NMR experiments in terms of the highly structurally sensitive C-H bond vector order parameters. Focusing on the glycerol backbone and choline headgroups, we showed that the order parameter comparison can be used to judge the atomistic resolution structural accuracy of the models. Accurate models, in turn, allow molecular dynamics simulations to be used as an interpretation tool that translates these NMR data into a dynamic three-dimensional representation of biomolecules in biologically relevant conditions. In addition to lipid bilayers in fully hydrated conditions, we reviewed previous experimental data for dehydrated bilayers and cholesterol-containing bilayers, and interpreted them with simulations. Although none of the existing models reached experimental accuracy, by critically comparing them we were able to distill relevant chemical information: (1) increase of choline order parameters indicates the P-N vector tilting more parallel to the membrane, and (2) cholesterol induces only minor changes to the PC (glycerol backbone) structure. This work has been done as a fully open collaboration, using nmrlipids.blogspot.fi as a communication platform; all the scientific contributions were made publicly on this blog. During the open research process, the repository holding our simulation trajectories and files ( https

  15. Toward Atomistic Resolution Structure of Phosphatidylcholine Headgroup and Glycerol Backbone at Different Ambient Conditions†

    PubMed Central

    2015-01-01

    Phospholipids are essential building blocks of biological membranes. Despite a vast amount of very accurate experimental data, the atomistic resolution structures sampled by the glycerol backbone and choline headgroup in phoshatidylcholine bilayers are not known. Atomistic resolution molecular dynamics simulations have the potential to resolve the structures, and to give an arrestingly intuitive interpretation of the experimental data, but only if the simulations reproduce the data within experimental accuracy. In the present work, we simulated phosphatidylcholine (PC) lipid bilayers with 13 different atomistic models, and compared simulations with NMR experiments in terms of the highly structurally sensitive C–H bond vector order parameters. Focusing on the glycerol backbone and choline headgroups, we showed that the order parameter comparison can be used to judge the atomistic resolution structural accuracy of the models. Accurate models, in turn, allow molecular dynamics simulations to be used as an interpretation tool that translates these NMR data into a dynamic three-dimensional representation of biomolecules in biologically relevant conditions. In addition to lipid bilayers in fully hydrated conditions, we reviewed previous experimental data for dehydrated bilayers and cholesterol-containing bilayers, and interpreted them with simulations. Although none of the existing models reached experimental accuracy, by critically comparing them we were able to distill relevant chemical information: (1) increase of choline order parameters indicates the P–N vector tilting more parallel to the membrane, and (2) cholesterol induces only minor changes to the PC (glycerol backbone) structure. This work has been done as a fully open collaboration, using nmrlipids.blogspot.fi as a communication platform; all the scientific contributions were made publicly on this blog. During the open research process, the repository holding our simulation trajectories and files (https

  16. Effect of Liquid-Crystalline Epoxy Backbone Structure on Thermal Conductivity of Epoxy-Alumina Composites

    NASA Astrophysics Data System (ADS)

    Giang, Thanhkieu; Kim, Jinhwan

    2016-06-01

    In a series of papers published recently, we clearly demonstrated that the most important factor governing the thermal conductivity of epoxy-Al2O3 composites is the backbone structure of the epoxy. In this study, three more epoxies based on diglycidyl ester-terminated liquid-crystalline epoxy (LCE) have been synthesized to draw conclusions regarding the effect of the epoxy backbone structure on the thermal conductivity of epoxy-alumina composites. The synthesized structures were characterized by proton nuclear magnetic resonance (1H-NMR) and Fourier-transform infrared (FT-IR) spectroscopy. Differential scanning calorimetry, thermogravimetric analysis, and optical microscopy were also employed to examine the thermal and optical properties of the synthesized LCEs and the cured composites. All three LCE resins exhibited typical liquid-crystalline behaviors: clear solid crystalline state below the melting temperature (T m), sharp crystalline melting at T m, and transition to nematic phase above T m with consequent isotropic phase above the isotropic temperature (T i). The LCE resins displayed distinct nematic liquid-crystalline phase over a wide temperature range and retained liquid-crystalline phase after curing, with high thermal conductivity of the resulting composite. The thermal conductivity values ranged from 3.09 W/m-K to 3.89 W/m-K for LCE-Al2O3 composites with 50 vol.% filler loading. The steric effect played a governing role in the difference. The neat epoxy resin thermal conductivity was obtained as 0.35 W/m-K to 0.49 W/m-K based on analysis using the Agari-Uno model. The results clearly support the objective of this study in that the thermal conductivity of the LCE-containing networks strongly depended on the epoxy backbone structure and the degree of ordering in the cured network.

  17. The structure of the carbohydrate backbone of the lipopolysaccharide of Pectinatus frisingensis strain VTT E-79104.

    PubMed

    Vinogradov, Evgeny; Li, Jianjun; Sadovskaya, Irina; Jabbouri, Said; Helander, Ilkka M

    2004-06-22

    The structure of the carbohydrate backbone of the lipopolysaccharide from Pectinatus frisingensis strain VTT E-79104 was analyzed using chemical degradations, NMR spectroscopy, mass spectrometry, and chemical methods. The LPS contains two major structural variants, differing in the presence or absence of an octasaccharide fragment. The largest structure of the carbohydrate backbone of the LPS, that could be deduced from experimental results, consists of 20 monosaccharides arranged in a nonrepetitive sequence: [carbohydrate structure: see text] where R is H or 4-O-Me-alpha-L-Fuc-(1-2)-4-O-Me-beta-Hep-(1-3)-alpha-GlcNAc-(1-2)-beta-Man-(1-3)-beta-ManNAc-(1-4)-alpha-Gal-(1-4)-beta-Hep-(1-3)-beta-GalNAc-(1- where Hep is a residue of D-glycero-D-galacto-heptose; all monosaccharides have the D-configuration except for 4-O-Me-L-Fuc and L-Ara4N. This structure is architecturally similar to the oligosaccharide system reported previously in P. frisingensis VTT E-82164 LPS, but differs from the latter in composition and also in the size of the outer region. PMID:15183738

  18. Correlation between protein secondary structure, backbone bond angles, and side-chain orientations

    NASA Astrophysics Data System (ADS)

    Lundgren, Martin; Niemi, Antti J.

    2012-08-01

    We investigate the fine structure of the sp3 hybridized covalent bond geometry that governs the tetrahedral architecture around the central Cα carbon of a protein backbone, and for this we develop new visualization techniques to analyze high-resolution x-ray structures in the Protein Data Bank. We observe that there is a correlation between the deformations of the ideal tetrahedral symmetry and the local secondary structure of the protein. We propose a universal coarse-grained energy function to describe the ensuing side-chain geometry in terms of the Cβ carbon orientations. The energy function can model the side-chain geometry with a subatomic precision. As an example we construct the Cα-Cβ structure of HP35 chicken villin headpiece. We obtain a configuration that deviates less than 0.4 Å in root-mean-square distance from the experimental x-ray structure.

  19. Structure and Assembly of Group B Streptococcus Pilus 2b Backbone Protein

    PubMed Central

    Cozzi, Roberta; Malito, Enrico; Lazzarin, Maddalena; Nuccitelli, Annalisa; Castagnetti, Andrea; Bottomley, Matthew J.; Margarit, Immaculada; Maione, Domenico; Rinaudo, C. Daniela

    2015-01-01

    Group B Streptococcus (GBS) is a major cause of invasive disease in infants. Like other Gram-positive bacteria, GBS uses a sortase C-catalyzed transpeptidation mechanism to generate cell surface pili from backbone and ancillary pilin precursor substrates. The three pilus types identified in GBS contain structural subunits that are highly immunogenic and are promising candidates for the development of a broadly-protective vaccine. Here we report the X-ray crystal structure of the backbone protein of pilus 2b (BP-2b) at 1.06Å resolution. The structure reveals a classical IgG-like fold typical of the pilin subunits of other Gram-positive bacteria. The crystallized portion of the protein (residues 185-468) encompasses domains D2 and D3 that together confer high stability to the protein due to the presence of an internal isopeptide bond within each domain. The D2+D3 region, lacking the N-terminal D1 domain, was as potent as the entire protein in conferring protection against GBS challenge in a well-established mouse model. By site-directed mutagenesis and complementation studies in GBS knock-out strains we identified the residues and motives essential for assembly of the BP-2b monomers into high-molecular weight complexes, thus providing new insights into pilus 2b polymerization. PMID:25942637

  20. NMR Structure Determination for Larger Proteins Using Backbone-Only Data

    PubMed Central

    Raman, Srivatsan; Lange, Oliver F.; Rossi, Paolo; Tyka, Michael; Wang, Xu; Aramini, James; Liu, Gaohua; Ramelot, Theresa; Eletsky, Alexander; Szyperski, Thomas; Kennedy, Michael; Prestegard, James; Montelione, Gaetano T.; Baker, David

    2010-01-01

    Conventional protein structure determination from nuclear magnetic resonance data relies heavily on side-chain proton-proton distances. The necessary side-chain resonance assignment, however, is labor intensive and prone to error. Here we show that structures can be accurately determined without NMR information on the sidechains for proteins up to 25 kDa by incorporating backbone chemical shifts, residual dipolar couplings, and amide proton distances into the Rosetta protein structure modelling methodology. These data, which are too sparse for conventional methods, serve only to guide conformational search towards the lowest energy conformations in the folding landscape; the details of the computed models are determined by the physical chemistry implicit in the Rosetta all atom energy function. The new method is not hindered by the deuteration required to suppress nuclear relaxation processes for proteins greater than 15 kDa, and should enable routine NMR structure determination for larger proteins. PMID:20133520

  1. Statistical mechanics of protein allostery: Roles of backbone and side-chain structural fluctuations

    NASA Astrophysics Data System (ADS)

    Itoh, Kazuhito; Sasai, Masaki

    2011-03-01

    A statistical mechanical model of allosteric transition of proteins is developed by extending the structure-based model of protein folding to cases that a protein has two different native conformations. Partition function is calculated exactly within the model and free-energy surfaces associated with allostery are derived. In this paper, the model of allosteric transition proposed in a previous paper [Proc. Natl. Acad. Sci. U.S.A 134, 7775 (2010)] is reformulated to describe both fluctuation in side-chain configurations and that in backbone structures in a balanced way. The model is applied to example proteins, Ras, calmodulin, and CheY: Ras undergoes the allosteric transition between guanosine diphosphate (GDP)-bound and guanosine triphosphate (GTP)-bound forms, and the model results show that the GDP-bound form is stabilized enough to prevent unnecessary signal transmission, but the conformation in the GTP-bound state bears large fluctuation in side-chain configurations, which may help to bind multiple target proteins for multiple pathways of signaling. The calculated results of calmodulin show the scenario of sequential ordering in Ca2 + binding and the associated allosteric conformational change, which are realized though the sequential appearing of pre-existing structural fluctuations, i.e., fluctuations to show structures suitable to bind Ca2 + before its binding. Here, the pre-existing fluctuations to accept the second and third Ca2 + ions are dominated by the side-chain fluctuation. In CheY, the calculated side-chain fluctuation of Tyr106 is coordinated with the backbone structural change in the β4-α4 loop, which explains the pre-existing Y-T coupling process in this protein. Ability of the model to explain allosteric transitions of example proteins supports the view that the large entropic effects lower the free-energy barrier of allosteric transition.

  2. Proton NMR assignments and regular backbone structure of bovine pancreatic ribonuclease A in aqueous solution

    SciTech Connect

    Robertson, A.D. ); Purisima, E.O. Cornell Univ., Ithaca, NY ); Eastman, M.A.; Scheraga, H.A. )

    1989-07-11

    Proton NMR assignments have been made for 121 of the 124 residues of bovine pancreatic ribonuclease A (RNase A). During the first stage of assignment, COSY and relayed COSY data were used to identify 40 amino acid spin systems belonging to alanine, valine, threonine, isoleucine, and serine residues. Approximately 60 other NH-{alpha}CH-{beta}CH systems were also identified but not assigned to specific amino acid type. NOESY data then were used to connect sequentially neighboring spin systems; approximately 475 of the possible 700 resonances in RNase A were assigned in this way. The authors' assignments agree with those for 20 residues assigned previously. NOESY correlations were used to identify regular backbone structure elements in RNase A, which are very similar to those observed in X-ray crystallographic studies.

  3. Solution structure and backbone dynamics of Mason-Pfizer monkey virus (MPMV) nucleocapsid protein.

    PubMed Central

    Gao, Y.; Kaluarachchi, K.; Giedroc, D. P.

    1998-01-01

    Retroviral nucleocapsid proteins (NCPs) are CCHC-type zinc finger proteins that mediate virion RNA binding activities associated with retrovirus assembly and genomic RNA encapsidation. Mason-Pfizer monkey virus (MPMV), a type D retrovirus, encodes a 96-amino acid nucleocapsid protein, which contains two Cys-X2-Cys-X4-His-X4-Cys (CCHC) zinc fingers connected by an unusually long 15-amino acid linker. Homonuclear, two-dimensional sensitivity-enhanced 15N-1H, three-dimensional 15N-1H, and triple resonance NMR spectroscopy have been used to determine the solution structure and residue-specific backbone dynamics of the structured core domain of MPMV NCP containing residues 21-80. Structure calculations and spectral density mapping of N-H bond vector mobility reveal that MPMV NCP 21-80 is best described as two independently folded, rotationally uncorrelated globular domains connected by a seven-residue flexible linker consisting of residues 42-48. The N-terminal CCHC zinc finger domain (residues 24-37) appears to adopt a fold like that described previously for HIV-1 NCP; however, residues within this domain and the immediately adjacent linker region (residues 38-41) are characterized by extensive conformational averaging on the micros-ms time scale at 25 degrees C. In contrast to other NCPs, residues 49-77, which includes the C-terminal CCHC zinc-finger (residues 53-66), comprise a well-folded globular domain with the Val49-Pro-Gly-Leu52 sequence and C-terminal tail residues 67-77 characterized by amide proton exchange properties and 15N R1, R2, and (1H-15N) NOE values indistinguishable to residues in the core C-terminal finger. Twelve refined structural models of MPMV NCP residues 49-80 (pairwise backbone RMSD of 0.77 A) reveal that the side chains of the conserved Pro50 and Trp62 are in van der Waals contact with one another. Residues 70-73 in the C-terminal tail adopt a reverse turn-like structure. Ile77 is involved in extensive van der Waals contact with the core

  4. Characterization of the structure and melting of DNAs containing backbone nicks and gaps

    SciTech Connect

    Snowden-Ifft, E.A.; Wemmer, D.E. )

    1990-06-26

    A DNA molecule containing a gap (a missing phosphate) has been examined and compared to two other molecules of the same sequence, one containing a nick (a phosphorylated gap) and the other a normal duplex containing no break in the backbone. A second gapped sequence was also compared to a normal duplex of the same sequence. The molecules containing nicks or gaps were generated as dumbbell molecules, short helices closed by a loop at each end. The dumbbells were formed by the association of two hairpins with self-complementary dangling 5'-ends. Nuclear magnetic resonance was used to monitor the melting transition and to probe structural differences between molecules. Under the conditions used here no change in stability was observed upon phosphorylation of the gap. Structural changes upon phosphorylation of a gap or closure of a nick were minimal and were localized to the region immediately around the gap or nick. Two transitions can be observed as a gapped or nicked molecule melts, although the resolution of the two transitions varies with the salt concentration. At moderate to high salt (greater than or equal to 30 mM) the molecule melts essentially all at once. At low salt the two transitions occur at temperatures that differ by as much as 15 degrees C. In addition, comparison with other NMR melting studies indicates that the duplex formed by the overlap of the dangling ends of the hairpins is stabilized relative to a free duplex of the same sequence, probably by stacking onto the hairpin stem.

  5. A Multi-Objective Approach for Protein Structure Prediction Based on an Energy Model and Backbone Angle Preferences

    PubMed Central

    Tsay, Jyh-Jong; Su, Shih-Chieh; Yu, Chin-Sheng

    2015-01-01

    Protein structure prediction (PSP) is concerned with the prediction of protein tertiary structure from primary structure and is a challenging calculation problem. After decades of research effort, numerous solutions have been proposed for optimisation methods based on energy models. However, further investigation and improvement is still needed to increase the accuracy and similarity of structures. This study presents a novel backbone angle preference factor, which is one of the factors inducing protein folding. The proposed multiobjective optimisation approach simultaneously considers energy models and backbone angle preferences to solve the ab initio PSP. To prove the effectiveness of the multiobjective optimisation approach based on the energy models and backbone angle preferences, 75 amino acid sequences with lengths ranging from 22 to 88 amino acids were selected from the CB513 data set to be the benchmarks. The data sets were highly dissimilar, therefore indicating that they are meaningful. The experimental results showed that the root-mean-square deviation (RMSD) of the multiobjective optimization approach based on energy model and backbone angle preferences was superior to those of typical energy models, indicating that the proposed approach can facilitate the ab initio PSP. PMID:26151847

  6. Solution structure and backbone dynamics of streptopain: insight into diverse substrate specificity.

    PubMed

    Wang, Chih-Chieh; Houng, Hsiang-Chee; Chen, Chun-Liang; Wang, Pei-Ju; Kuo, Chih-Feng; Lin, Yee-Shin; Wu, Jiunn-Jong; Lin, Ming T; Liu, Ching-Chuan; Huang, Wenya; Chuang, Woei-Jer

    2009-04-17

    Streptococcal pyrogenic exotoxin B (SPE B) is a cysteine protease expressed by Streptococcus pyogenes. The D9N, G163S, G163S/A172S, and G239D mutant proteins were expressed to study the effect of the allelic variants on their protease activity. In contrast to other mutants, the G239D mutant was approximately 12-fold less active. The Gly-239 residue is located within the C-terminal S230-G239 region, which cannot be observed in the x-ray structure. The three-dimensional structure and backbone dynamics of the 28-kDa mature SPE B (mSPE B) were determined. Unlike the x-ray structure of the 40-kDa zymogen SPE B (proSPE B), we observed the interactions between the C-terminal loop and the active site residues in mSPE B. The structural differences between mSPE B and proSPE B were the conformation of the C-terminal loop and the orientation of the catalytic His-195 residue, suggesting that activation and inactivation of SPE B is involved in the His-195 side-chain rotation. Dynamics analysis of mSPE B and the mSPE B/inhibitor complexes showed that the catalytic and C-terminal loops were the most flexible regions with low order parameter values of 0.5 to 0.8 and exhibited the motion on the ps/ns timescale. These findings suggest that the flexible C-terminal loop of SPE B may play an important role in controlling the substrate binding, resulting in its broad substrate specificity. PMID:19237546

  7. Unconventional N-H…N Hydrogen Bonds Involving Proline Backbone Nitrogen in Protein Structures.

    PubMed

    Deepak, R N V Krishna; Sankararamakrishnan, Ramasubbu

    2016-05-10

    Contrary to DNA double-helical structures, hydrogen bonds (H-bonds) involving nitrogen as the acceptor are not common in protein structures. We systematically searched N-H…N H-bonds in two different sets of protein structures. Data set I consists of neutron diffraction and ultrahigh-resolution x-ray structures (0.9 Å resolution or better) and the hydrogen atom positions in these structures were determined experimentally. Data set II contains structures determined using x-ray diffraction (resolution ≤ 1.8 Å) and the positions of hydrogen atoms were generated using a computational method. We identified 114 and 14,347 potential N-H…N H-bonds from these two data sets, respectively, and 56-66% of these were of the Ni+1-Hi+1…Ni type, with Ni being the proline backbone nitrogen. To further understand the nature of such unusual contacts, we performed quantum chemical calculations on the model compound N-acetyl-L-proline-N-methylamide (Ace-Pro-NMe) with coordinates taken from the experimentally determined structures. A potential energy profile generated by varying the ψ dihedral angle in Ace-Pro-NMe indicates that the conformation with the N-H…N H-bond is the most stable. An analysis of H-bond-forming proline residues reveals that more than 30% of the proline carbonyl groups are also involved in n → π(∗) interactions with the carbonyl carbon of the preceding residue. Natural bond orbital analyses demonstrate that the strength of N-H…N H-bonds is less than half of that observed for a conventional H-bond. This study clearly establishes the H-bonding capability of proline nitrogen and its prevalence in protein structures. We found many proteins with multiple instances of H-bond-forming prolines. With more than 15% of all proline residues participating in N-H…N H-bonds, we suggest a new, to our knowledge, structural role for proline in providing stability to loops and capping regions of secondary structures in proteins. PMID:27166805

  8. STARD6 on steroids: solution structure, multiple timescale backbone dynamics and ligand binding mechanism

    PubMed Central

    Létourneau, Danny; Bédard, Mikaël; Cabana, Jérôme; Lefebvre, Andrée; LeHoux, Jean-Guy; Lavigne, Pierre

    2016-01-01

    START domain proteins are conserved α/β helix-grip fold that play a role in the non-vesicular and intracellular transport of lipids and sterols. The mechanism and conformational changes permitting the entry of the ligand into their buried binding sites is not well understood. Moreover, their functions and the identification of cognate ligands is still an active area of research. Here, we report the solution structure of STARD6 and the characterization of its backbone dynamics on multiple time-scales through 15N spin-relaxation and amide exchange studies. We reveal for the first time the presence of concerted fluctuations in the Ω1 loop and the C-terminal helix on the microsecond-millisecond time-scale that allows for the opening of the binding site and ligand entry. We also report that STARD6 binds specifically testosterone. Our work represents a milestone for the study of ligand binding mechanism by other START domains and the elucidation of the biological function of STARD6. PMID:27340016

  9. STARD6 on steroids: solution structure, multiple timescale backbone dynamics and ligand binding mechanism.

    PubMed

    Létourneau, Danny; Bédard, Mikaël; Cabana, Jérôme; Lefebvre, Andrée; LeHoux, Jean-Guy; Lavigne, Pierre

    2016-01-01

    START domain proteins are conserved α/β helix-grip fold that play a role in the non-vesicular and intracellular transport of lipids and sterols. The mechanism and conformational changes permitting the entry of the ligand into their buried binding sites is not well understood. Moreover, their functions and the identification of cognate ligands is still an active area of research. Here, we report the solution structure of STARD6 and the characterization of its backbone dynamics on multiple time-scales through (15)N spin-relaxation and amide exchange studies. We reveal for the first time the presence of concerted fluctuations in the Ω1 loop and the C-terminal helix on the microsecond-millisecond time-scale that allows for the opening of the binding site and ligand entry. We also report that STARD6 binds specifically testosterone. Our work represents a milestone for the study of ligand binding mechanism by other START domains and the elucidation of the biological function of STARD6. PMID:27340016

  10. Conformation Dependence of Backbone Geometry in Proteins

    PubMed Central

    Berkholz, Donald S.; Shapovalov, Maxim V.; Dunbrack, Roland L.; Karplus, P. Andrew

    2009-01-01

    Summary Protein structure determination and predictive modeling have long been guided by the paradigm that the peptide backbone has a single, context-independent ideal geometry. Both quantum-mechanics calculations and empirical analyses have shown this is an incorrect simplification in that backbone covalent geometry actually varies systematically as a function of the Φ and Ψ backbone dihedral angles. Here, we use a nonredundant set of ultrahigh-resolution protein structures to define these conformation-dependent variations. The trends have a rational, structural basis that can be explained by avoidance of atomic clashes or optimization of favorable electrostatic interactions. To facilitate adoption of this new paradigm, we have created a conformation-dependent library of covalent bond lengths and bond angles and shown that it has improved accuracy over existing methods without any additional variables to optimize. Protein structures derived both from crystallographic refinement and predictive modeling both stand to benefit from incorporation of the new paradigm. PMID:19836332

  11. Improving prediction of secondary structure, local backbone angles, and solvent accessible surface area of proteins by iterative deep learning

    PubMed Central

    Heffernan, Rhys; Paliwal, Kuldip; Lyons, James; Dehzangi, Abdollah; Sharma, Alok; Wang, Jihua; Sattar, Abdul; Yang, Yuedong; Zhou, Yaoqi

    2015-01-01

    Direct prediction of protein structure from sequence is a challenging problem. An effective approach is to break it up into independent sub-problems. These sub-problems such as prediction of protein secondary structure can then be solved independently. In a previous study, we found that an iterative use of predicted secondary structure and backbone torsion angles can further improve secondary structure and torsion angle prediction. In this study, we expand the iterative features to include solvent accessible surface area and backbone angles and dihedrals based on Cα atoms. By using a deep learning neural network in three iterations, we achieved 82% accuracy for secondary structure prediction, 0.76 for the correlation coefficient between predicted and actual solvent accessible surface area, 19° and 30° for mean absolute errors of backbone φ and ψ angles, respectively, and 8° and 32° for mean absolute errors of Cα-based θ and τ angles, respectively, for an independent test dataset of 1199 proteins. The accuracy of the method is slightly lower for 72 CASP 11 targets but much higher than those of model structures from current state-of-the-art techniques. This suggests the potentially beneficial use of these predicted properties for model assessment and ranking. PMID:26098304

  12. Slow dynamics of a protein backbone in molecular dynamics simulation revealed by time-structure based independent component analysis

    SciTech Connect

    Naritomi, Yusuke; Fuchigami, Sotaro

    2013-12-07

    We recently proposed the method of time-structure based independent component analysis (tICA) to examine the slow dynamics involved in conformational fluctuations of a protein as estimated by molecular dynamics (MD) simulation [Y. Naritomi and S. Fuchigami, J. Chem. Phys. 134, 065101 (2011)]. Our previous study focused on domain motions of the protein and examined its dynamics by using rigid-body domain analysis and tICA. However, the protein changes its conformation not only through domain motions but also by various types of motions involving its backbone and side chains. Some of these motions might occur on a slow time scale: we hypothesize that if so, we could effectively detect and characterize them using tICA. In the present study, we investigated slow dynamics of the protein backbone using MD simulation and tICA. The selected target protein was lysine-, arginine-, ornithine-binding protein (LAO), which comprises two domains and undergoes large domain motions. MD simulation of LAO in explicit water was performed for 1 μs, and the obtained trajectory of C{sub α} atoms in the backbone was analyzed by tICA. This analysis successfully provided us with slow modes for LAO that represented either domain motions or local movements of the backbone. Further analysis elucidated the atomic details of the suggested local motions and confirmed that these motions truly occurred on the expected slow time scale.

  13. Slow dynamics of a protein backbone in molecular dynamics simulation revealed by time-structure based independent component analysis

    NASA Astrophysics Data System (ADS)

    Naritomi, Yusuke; Fuchigami, Sotaro

    2013-12-01

    We recently proposed the method of time-structure based independent component analysis (tICA) to examine the slow dynamics involved in conformational fluctuations of a protein as estimated by molecular dynamics (MD) simulation [Y. Naritomi and S. Fuchigami, J. Chem. Phys. 134, 065101 (2011)]. Our previous study focused on domain motions of the protein and examined its dynamics by using rigid-body domain analysis and tICA. However, the protein changes its conformation not only through domain motions but also by various types of motions involving its backbone and side chains. Some of these motions might occur on a slow time scale: we hypothesize that if so, we could effectively detect and characterize them using tICA. In the present study, we investigated slow dynamics of the protein backbone using MD simulation and tICA. The selected target protein was lysine-, arginine-, ornithine-binding protein (LAO), which comprises two domains and undergoes large domain motions. MD simulation of LAO in explicit water was performed for 1 μs, and the obtained trajectory of Cα atoms in the backbone was analyzed by tICA. This analysis successfully provided us with slow modes for LAO that represented either domain motions or local movements of the backbone. Further analysis elucidated the atomic details of the suggested local motions and confirmed that these motions truly occurred on the expected slow time scale.

  14. Backbone structures in human milk oligosaccharides: trans-glycosylation by metagenomic β-N-acetylhexosaminidases.

    PubMed

    Nyffenegger, Christian; Nordvang, Rune Thorbjørn; Zeuner, Birgitte; Łężyk, Mateusz; Difilippo, Elisabetta; Logtenberg, Madelon J; Schols, Henk A; Meyer, Anne S; Mikkelsen, Jørn Dalgaard

    2015-10-01

    This paper describes the discovery and characterization of two novel β-N-acetylhexosaminidases HEX1 and HEX2, capable of catalyzing the synthesis of human milk oligosaccharides (HMO) backbone structures with fair yields using chitin oligomers as β-N-acetylglucosamine (GlcNAc) donor. The enzyme-encoding genes were identified by functional screening of a soil-derived metagenomic library. The β-N-acetylhexosaminidases were expressed in Escherichia coli with an N-terminal His6-tag and were purified by nickel affinity chromatography. The sequence similarities of the enzymes with their respective closest homologues are 59 % for HEX1 and 51 % for HEX2 on the protein level. Both β-N-acetylhexosaminidases are classified into glycosyl hydrolase family 20 (GH 20) are able to hydrolyze para-nitrophenyl-β-N-acetylglucosamine (pNP-GlcNAc) as well as para-nitrophenyl-β-N-acetylgalactosamine (pNP-GalNAc) and exhibit pH optima of 8 and 6 for HEX1 and HEX2, respectively. The enzymes are able to hydrolyze N-acetylchitooligosaccharides with a degree of polymerization of two, three, and four. The major findings were, that HEX1 and HEX2 catalyze trans-glycosylation reactions with lactose as acceptor, giving rise to the human milk oligosaccharide precursor lacto-N-triose II (LNT2) with yields of 2 and 8 % based on the donor substrate. In total, trans-glycosylation reactions were tested with the disaccharide acceptors β-lactose, sucrose, and maltose, as well as with the monosaccharides galactose and glucose resulting in the successful attachment of GlcNAc to the acceptor in all cases. PMID:25843303

  15. Influence of the backbone structure on the release of bioactive volatiles from maleic acid-based polymer conjugates.

    PubMed

    Berthier, Damien L; Paret, Nicolas; Trachsel, Alain; Herrmann, Andreas

    2010-11-17

    Poly(maleic acid monoester)-based β-mercapto ketones were synthesized and investigated as potential delivery systems for the controlled release of bioactive, volatile, α,β-unsaturated enones (such as damascones and damascenones) by retro 1,4-addition. The bioconjugates were prepared in a one-pot synthesis using 2-mercaptoethanol as a linker. The thiol group of 2-mercaptoethanol adds to the double bond of the enone to form a β-mercapto ketone, which was then grafted via nucleophilic ring-opening of the remaining alcohol function onto a series of alternating copolymers of maleic anhydride and 1-octadecene, ethylene, isobutylene, and methyl vinyl ether. The influence of copolymer backbones on the release of δ-damascone was investigated in buffered aqueous solution as a function of pH and time. In the presence of a cationic surfactant, the polymer conjugates were transferred from an aqueous medium to a cotton surface. The deposition and the release of δ-damascone from the cotton surface as a function of the polymer backbone structure were measured by fluorescence spectroscopy and dynamic headspace analysis, respectively. All polymer conjugates were found to deliver higher amounts of the volatile into the headspace than the reference consisting of unmodified δ-damascone. Polymers with a hydrophobic backbone were generally efficiently deposited on the cotton surface, but released δ-damascone only moderately in solution. Conjugates with a more hydrophilic backbone release the active compound more efficiently in water, but are deposited to a lower extent onto the target surface. A good balance of the hydrophobicity and hydrophilicity of the polymer backbone is the key factor to maximize the deposition of the conjugates on the target surface and to optimize the release of the bioactive volatiles. PMID:20936844

  16. Protein inhibitors of serine proteinases: role of backbone structure and dynamics in controlling the hydrolysis constant.

    PubMed

    Song, Jikui; Markley, John L

    2003-05-13

    Standard mechanism protein inhibitors of serine proteinases bind as substrates and are cleaved by cognate proteinases at their reactive sites. The hydrolysis constant for this cleavage reaction at the P(1)-P(1)' peptide bond (K(hyd)) is determined by the relative concentrations at equilibrium of the "intact" (uncleaved, I) and "modified" (reactive site cleaved, I*) forms of the inhibitor. The pH dependence of K(hyd) can be explained in terms of a pH-independent term, K(hyd) degrees, plus the proton dissociation constants of the newly formed amino and carboxylate groups at the cleavage site. Two protein inhibitors that differ from one another by a single residue substitution have been found to have K(hyd) degrees values that differ by a factor of 5 [Ardelt, W., and Laskowski, M., Jr. (1991) J. Mol. Biol. 220, 1041-1052]: turkey ovomucoid third domain (OMTKY3) has K(hyd) degrees = 1.0, and Indian peafowl ovomucoid third domain (OMIPF3), which differs from OMTKY3 by the substitution P(2)'-Tyr(20)His, has K(hyd) degrees = 5.15. What mechanism is responsible for this small difference? Is it structural (enthalpic) or dynamic (entropic)? Does the mutation affect the free energy of the I state, the I* state, or both? We have addressed these questions through NMR investigations of the I and I forms of OMTKY3 and OMIPF3. Information about structure was derived from measurements of NMR chemical shift changes and trans-hydrogen-bond J-couplings; information about dynamics was obtained through measurements of (15)N relaxation rates and (1)H-(15)N heteronuclear NOEs with model-free analysis of the results. Although the I forms of each variant are more dynamic than the corresponding I forms, the study revealed no appreciable difference in the backbone dynamics of either intact inhibitor (OMIPF3 vs OMTKY3) or modified inhibitor (OMIPF3* vs OMTKY3*). Instead, changes in chemical shifts and trans-hydrogen-bond J-couplings suggested that the K(hyd) degrees difference arises from

  17. Backbone Structure of Transmembrane Domain IX of the Na+/Proline Transporter PutP of Escherichia coli

    PubMed Central

    Hilger, Daniel; Polyhach, Yevhen; Jung, Heinrich; Jeschke, Gunnar

    2009-01-01

    Abstract The backbone structure is determined by site-directed spin labeling, double electron electron resonance measurements of distances, and modeling in terms of a helix-loop-helix construct for a transmembrane domain that is supposed to line the translocation pathway in the 54.3 kDa Na+/proline symporter PutP of Escherichia coli. The conformational distribution of the spin labels is accounted for by a rotamer library. An ensemble of backbone models with a root mean-square deviation of less than 2 Å is obtained. These models exhibit a pronounced kink near residue T341, which is involved in substrate binding. The kink may be associated with a hinge that allows the protein to open and close an inwardly oriented cavity. PMID:19134477

  18. RNA-Binding Affinities and Crystal Structure of Oligonucleotides Containing Five-Atom Amide-Based Backbone Structures

    SciTech Connect

    Pallan, Pradeep S.; von Matt, Peter; Wilds, Christopher J.; Altmann, Karl-Heinz; Egli, Martin

    2010-03-08

    Among the hundreds of nucleic acid analogues that have been studied over the last two decades only very few exhibit backbones with linkers between residues that are either shorter or longer than the four-atom linker O3{prime}-P-O5{prime}-C5{prime} connecting sugar ring moieties in DNA and RNA. 2{prime}-Deoxyribonucleoside dimers connected by a five-atom linker O3{prime}-CH*(CH{sub 3})-CO-NH-CH{sub 2} (* designates a chiral center) were reported to lead to only a slight destabilization of RNA-DNA hybrids in which the DNA strand contained one or several of these amide-linked dimers (De Napoli, L., Iadonisi, A., Montesarchio, D., Varra, M., and Piccialli, G. (1995) Synthesis of thymidine dimers containing a new internucleosidic amide linkage and their incorporation into oligodeoxyribonucleotides, Bioorg. Med. Chem. Lett. 5, 1647-1652). To analyze the influence of various chemistries of such five-atom amide linkers on the RNA-binding affinity of modified DNA strands, we have synthesized five different amide-linked dimers, including structures with homochiral linkers of the type X3{prime}-C*H(CH{sub 3})-CO-NH-CH{sub 2} (X = O, CH{sub 2}) as well as the corresponding analogues carrying methoxy groups at the 2{prime}-position of the 3{prime}-nucleosides. We have conducted a detailed thermodynamic analysis of duplex formation between the modified DNA and RNA, with the DNA strands containing between one and seven consecutive modified dimers. Some of the five-atom-linked dimers lead to significantly higher RNA-binding affinities compared with that of native DNA. Interestingly, the linkers with opposite stereochemistry at the chiral center stabilize duplexes between the modified DNA and RNA to different degrees. CD spectroscopy in solution and a crystal structure of an RNA-DNA duplex with a single amide-linked dimer demonstrate that the longer amide backbones do not disrupt the duplex geometry. These observations provide further evidence that stable cross-pairing between two

  19. The backbone structure of the thermophilic Thermoanaerobacter tengcongensis ribose binding protein is essentially identical to its mesophilic E. coli homolog

    PubMed Central

    Cuneo, Matthew J; Tian, Yaji; Allert, Malin; Hellinga, Homme W

    2008-01-01

    Background Comparison of experimentally determined mesophilic and thermophilic homologous protein structures is an important tool for understanding the mechanisms that contribute to thermal stability. Of particular interest are pairs of homologous structures that are structurally very similar, but differ significantly in thermal stability. Results We report the X-ray crystal structure of a Thermoanaerobacter tengcongensis ribose binding protein (tteRBP) determined to 1.9 Å resolution. We find that tteRBP is significantly more stable (appTm value ~102°C) than the mesophilic Escherichia coli ribose binding protein (ecRBP) (appTm value ~56°C). The tteRBP has essentially the identical backbone conformation (0.41 Å RMSD of 235/271 Cα positions and 0.65 Å RMSD of 270/271 Cα positions) as ecRBP. Classification of the amino acid substitutions as a function of structure therefore allows the identification of amino acids which potentially contribute to the observed thermal stability of tteRBP in the absence of large structural heterogeneities. Conclusion The near identity of backbone structures of this pair of proteins entails that the significant differences in their thermal stabilities are encoded exclusively by the identity of the amino acid side-chains. Furthermore, the degree of sequence divergence is strongly correlated with structure; with a high degree of conservation in the core progressing to increased diversity in the boundary and surface regions. Different factors that may possibly contribute to thermal stability appear to be differentially encoded in each of these regions of the protein. The tteRBP/ecRBP pair therefore offers an opportunity to dissect contributions to thermal stability by side-chains alone in the absence of large structural differences. PMID:18373848

  20. The backbone structure of the thermophilic Thermoanaerobacter tengcongensis ribose binding protein is essentially identical to its mesophilic E. coli homolog

    SciTech Connect

    Cuneo, Matthew J.; Tian, Yaji; Allert, Malin; Hellinga, Homme W.

    2008-10-27

    We report the X-ray crystal structure of a Thermoanaerobacter tengcongensis ribose binding protein (tteRBP) determined to 1.9 {angstrom} resolution. We find that tteRBP is significantly more stable ({sup app}T{sub m} value {approx} 102 C) than the mesophilic Escherichia coli ribose binding protein (ecRBP) ({sup app}T{sub m} value {approx} 56 C). The tteRBP has essentially the identical backbone conformation (0.41 {angstrom} RMSD of 235/271 C{sub {alpha}} positions and 0.65 {angstrom} RMSD of 270/271 C{sub {alpha}} positions) as ecRBP. Classification of the amino acid substitutions as a function of structure therefore allows the identification of amino acids which potentially contribute to the observed thermal stability of tteRBP in the absence of large structural heterogeneities.

  1. Mechanics and Chemistry: Sinle Molecule Bond Rupture Forces Correlate with Molecular Backbone Structure

    SciTech Connect

    Frei, M.; Hybertsen, M.; Aradhya, S.V.; Koentopp, M.; Venkataraman, L.

    2011-03-02

    We simultaneously measure conductance and force across nanoscale junctions. A new, two-dimensional histogram technique is introduced to statistically extract bond rupture forces from a large data set of individual junction elongation traces. For the case of Au point contacts, we find a rupture force of 1.4 {+-} 0.2 nN, which is in good agreement with previous measurements. We then study systematic trends for single gold metal-molecule-metal junctions for a series of molecules terminated with amine and pyridine linkers. For all molecules studied, single molecule junctions rupture at the Au-N bond. Selective binding of the linker group allows us to correlate the N-Au bond-rupture force to the molecular backbone. We find that the rupture force ranges from 0.8 nN for 4,4' bipyridine to 0.5 nN in 1,4 diaminobenzene. These experimental results are in excellent quantitative agreement with density functional theory based adiabatic molecular junction elongation and rupture calculations.

  2. Formation of Hierarchical Structure Composed of (Co/Ni)Mn-LDH Nanosheets on MWCNT Backbones for Efficient Electrocatalytic Water Oxidation.

    PubMed

    Jia, Gan; Hu, Yingfei; Qian, Qinfeng; Yao, Yingfang; Zhang, Shiying; Li, Zhaosheng; Zou, Zhigang

    2016-06-15

    Active, stable, and cost-effective electrocatalysts are attractive alternatives to the noble metal oxides that have been used in water splitting. The direct nucleation and growth of electrochemically active LDH materials on chemically modified MWCNTs exhibit considerable electrocatalytic activity toward oxygen evolution from water oxidation. CoMn-based and NiMn-based hybrids were synthesized using a facile chemical bath deposition method and the as-synthesized materials exhibited three-dimensional hierarchical configurations with tunable Co/Mn and Ni/Mn ratio. Benefiting from enhanced electrical conductivity with MWCNT backbones and LDH lamellar structure, the Co5Mn-LDH/MWCNT and Ni5Mn-LDH/MWCNT could generated a current density of 10 mA cm(-2) at overpotentials of ∼300 and ∼350 mV, respectively, in 1 M KOH. In addition, the materials also exhibited outstanding long-term electrocatalytic stability. PMID:27214293

  3. Structure of the exceptionally large nonrepetitive carbohydrate backbone of the lipopolysaccharide of Pectinatus frisingensis strain VTT E-82164.

    PubMed

    Vinogradov, Evgeny; Petersen, Bent O; Sadovskaya, Irina; Jabbouri, Said; Duus, Jens Ø; Helander, Ilkka M

    2003-07-01

    The structures of the oligosaccharides obtained after acetic acid hydrolysis and alkaline deacylation of the rough-type lipopolysaccharide (LPS) from Pectinatus frisingensis strain VTT E-82164 were analysed using NMR spectroscopy, MS and chemical methods. The LPS contains two major structural variants, differing by a decasaccharide fragment, and some minor variants lacking the terminal glucose residue. The largest structure of the carbohydrate backbone of the LPS that could be deduced from experimental results consists of 25 monosaccharides (including the previously found Ara4NP residue in lipid A) arranged in a well-defined nonrepetitive structure: We presume that the shorter variant with R1 = H represents the core-lipid A part of the LPS, and the additional fragment is present instead of the O-specific polysaccharide. Structures of this type have not been previously described. Analysis of the deacylation products obtained from the LPS of the smooth strain, VTT E-79100T, showed that it contains a very similar core but with one different glycosidic linkage. PMID:12846837

  4. Hidden Markov models that use predicted local structure for fold recognition: alphabets of backbone geometry.

    PubMed

    Karchin, Rachel; Cline, Melissa; Mandel-Gutfreund, Yael; Karplus, Kevin

    2003-06-01

    An important problem in computational biology is predicting the structure of the large number of putative proteins discovered by genome sequencing projects. Fold-recognition methods attempt to solve the problem by relating the target proteins to known structures, searching for template proteins homologous to the target. Remote homologs that may have significant structural similarity are often not detectable by sequence similarities alone. To address this, we incorporated predicted local structure, a generalization of secondary structure, into two-track profile hidden Markov models (HMMs). We did not rely on a simple helix-strand-coil definition of secondary structure, but experimented with a variety of local structure descriptions, following a principled protocol to establish which descriptions are most useful for improving fold recognition and alignment quality. On a test set of 1298 nonhomologous proteins, HMMs incorporating a 3-letter STRIDE alphabet improved fold recognition accuracy by 15% over amino-acid-only HMMs and 23% over PSI-BLAST, measured by ROC-65 numbers. We compared two-track HMMs to amino-acid-only HMMs on a difficult alignment test set of 200 protein pairs (structurally similar with 3-24% sequence identity). HMMs with a 6-letter STRIDE secondary track improved alignment quality by 62%, relative to DALI structural alignments, while HMMs with an STR track (an expanded DSSP alphabet that subdivides strands into six states) improved by 40% relative to CE. PMID:12784210

  5. NMR characterization of structure, backbone dynamics, and glutathione binding of the human macrophage migration inhibitory factor (MIF).

    PubMed

    Mühlhahn, P; Bernhagen, J; Czisch, M; Georgescu, J; Renner, C; Ross, A; Bucala, R; Holak, T A

    1996-10-01

    Human macrophage migration inhibitory factor is a 114 amino acid protein that belongs to the family of immunologic cytokines. Assignments of 1H, 15N, and 13C resonances have enabled the determination of the secondary structure of the protein, which consists of two alpha-helices (residues 18-31 and 89-72) and a central four-stranded beta-sheet. In the beta-sheet, two parallel beta-sheets are connected in an antiparallel sense. From the total of three cysteines present in the primary structure of MIF, none was found to form disulfide bridges. 1H-15N heteronuclear T1, T2, and steady-state NOE measurements indicate that the backbone of MIF exists in a rigid structure of limited conformational flexibility (on the nanosecond to picosecond time scale). Several residues located in the loop regions and at the N termini of two helices exhibit internal motions on the 1-3 ns time scale. The capacity to bind glutathione was investigated by titration of a uniform 15N-labeled sample and led us to conclude that MIF has, at best, very low affinity for glutathione. PMID:8897610

  6. NMR characterization of structure, backbone dynamics, and glutathione binding of the human macrophage migration inhibitory factor (MIF).

    PubMed Central

    Mühlhahn, P.; Bernhagen, J.; Czisch, M.; Georgescu, J.; Renner, C.; Ross, A.; Bucala, R.; Holak, T. A.

    1996-01-01

    Human macrophage migration inhibitory factor is a 114 amino acid protein that belongs to the family of immunologic cytokines. Assignments of 1H, 15N, and 13C resonances have enabled the determination of the secondary structure of the protein, which consists of two alpha-helices (residues 18-31 and 89-72) and a central four-stranded beta-sheet. In the beta-sheet, two parallel beta-sheets are connected in an antiparallel sense. From the total of three cysteines present in the primary structure of MIF, none was found to form disulfide bridges. 1H-15N heteronuclear T1, T2, and steady-state NOE measurements indicate that the backbone of MIF exists in a rigid structure of limited conformational flexibility (on the nanosecond to picosecond time scale). Several residues located in the loop regions and at the N termini of two helices exhibit internal motions on the 1-3 ns time scale. The capacity to bind glutathione was investigated by titration of a uniform 15N-labeled sample and led us to conclude that MIF has, at best, very low affinity for glutathione. PMID:8897610

  7. Backbone and side-chain (1)H, (15)N, (13)C assignment and secondary structure of BPSL1445 from Burkholderia pseudomallei.

    PubMed

    Quilici, Giacomo; Berardi, Andrea; Gaudesi, Davide; Gourlay, Louise J; Bolognesi, Martino; Musco, Giovanna

    2015-10-01

    BPSL1445 is a lipoprotein produced by the Gram-negative bacterium Burkholderia pseudomallei (B. pseudomallei), the etiological agent of melioidosis. Immunodetection assays against sera patients using protein microarray suggest BPSL1445 involvement in melioidosis. Herein we report backbone, side chain NMR assignment and secondary structure for the recombinant protein. PMID:25893672

  8. Bayesian probabilistic approach for predicting backbone structures in terms of protein blocks.

    PubMed

    de Brevern, A G; Etchebest, C; Hazout, S

    2000-11-15

    By using an unsupervised cluster analyzer, we have identified a local structural alphabet composed of 16 folding patterns of five consecutive C(alpha) ("protein blocks"). The dependence that exists between successive blocks is explicitly taken into account. A Bayesian approach based on the relation protein block-amino acid propensity is used for prediction and leads to a success rate close to 35%. Sharing sequence windows associated with certain blocks into "sequence families" improves the prediction accuracy by 6%. This prediction accuracy exceeds 75% when keeping the first four predicted protein blocks at each site of the protein. In addition, two different strategies are proposed: the first one defines the number of protein blocks in each site needed for respecting a user-fixed prediction accuracy, and alternatively, the second one defines the different protein sites to be predicted with a user-fixed number of blocks and a chosen accuracy. This last strategy applied to the ubiquitin conjugating enzyme (alpha/beta protein) shows that 91% of the sites may be predicted with a prediction accuracy larger than 77% considering only three blocks per site. The prediction strategies proposed improve our knowledge about sequence-structure dependence and should be very useful in ab initio protein modelling. PMID:11025540

  9. A non-intuitive design of a cyclic decapeptide library with unique backbone structural features.

    PubMed

    Paul, P K C

    2003-12-01

    An analysis of hydrogen bonding patterns of cyclic decapeptide (CDP) beta-sheet structures has resulted in a 'non-intuitive' design of cyclic decapeptides wherein their beta-turns and residue positions can be fixed by choosing 2 of the 10 residues, i.e. positions i and i+4, to be Prolines or N-substituted residues. This sequence relationship between the two Pro or N-substituted residues is shown to uniquely define the conformation of the CDP. Furthermore, this design of the 2 beta-turn, beta-sheet CDP structure is expected to be characterised by residues disposed in an exclusive fashion in which four residues are on one side of the ring, two on the other and the four corner residues in the beta-turn are in the plane of the ring. This opens up the possibility of fine-tuning the four residues facing one way and /or the two residues facing the other way such that a library containing a myriad of chemically diverse systems could be obtained. The design process along with the molecular modelling of specific CDP-s and the building of a CDP library are discussed in detail. PMID:14683511

  10. HMM-based prediction for protein structural motifs' two local properties: solvent accessibility and backbone torsion angles.

    PubMed

    Yu, Jianyong; Xiang, Leijun; Hong, Jiang; Zhang, Weidong

    2013-02-01

    Protein structure prediction is often assisted by predicting one-dimensional structural properties including relative solvent accessibility (RSA) surface and backbone torsion angles (BTA) of residues, and these two properties are continuously varying variables because proteins can move freely in a three-dimensional space. Instead of subdividing them into a few arbitrarily defined states that many popular approaches used, this paper proposes an integrated system for realvalue prediction of protein structural motifs' two local properties, based on the modified Hidden Markov Model that we previously presented. The model was used to capture the relevance of RSA and the dependency of BTA between adjacent residues along the local protein chain in motifs with definite probabilities. These two properties were predicted according to their own probability distribution. The method was applied to a protein fragment library. For nine different classes of motifs, real values of RSA were predicted with mean absolute error (MAE) of 0.122-0.175 and Pearson's correlation coefficient (PCC) of 0.623-0.714 between predicted and actual RSA. Meanwhile, real values of BTA were obtained with MAE of 8.5⁰-29.4⁰ for Φ angles, 11.2⁰-38.5⁰ for ψ angles and PCC of 0.601-0.716 for Φ, 0.597-0.713 for ψ. The results were compared with well-known Real-SPINE Server, and indicate the proposed method may at least serve as the foundation to obtain better local properties from structural motifs for protein structure prediction. PMID:22894152

  11. Variational identities and Hamiltonian structures

    SciTech Connect

    Ma Wenxiu

    2010-03-08

    This report is concerned with Hamiltonian structures of classical and super soliton hierarchies. In the classical case, basic tools are variational identities associated with continuous and discrete matrix spectral problems, targeted to soliton equations derived from zero curvature equations over general Lie algebras, both semisimple and non-semisimple. In the super case, a supertrace identity is presented for constructing Hamiltonian structures of super soliton equations associated with Lie superalgebras. We illustrate the general theories by the KdV hierarchy, the Volterra lattice hierarchy, the super AKNS hierarchy, and two hierarchies of dark KdV equations and dark Volterra lattices. The resulting Hamiltonian structures show the commutativity of each hierarchy discussed and thus the existence of infinitely many commuting symmetries and conservation laws.

  12. Role of monomer sequence and backbone structure in polypeptoid and polypeptide polymers for anti-fouling applications

    NASA Astrophysics Data System (ADS)

    Patterson, Anastasia; Rizis, Georgios; Wenning, Brandon; Finlay, John; Ober, Christopher; Segalman, Rachel

    Polymeric coatings rely on a fine balance of surface properties to achieve biofouling resistance. Bioinsipired polymers and oligomers provide a modular strategy for the inclusion of multiple functionalities with controlled architecture, sequence and surface properties. In this work, polypeptoid and polypeptide functionalized coatings based on PEO and PDMS block copolymers were compared with respect to surface presentation and fouling by Ulva linza. While polypeptoids and polypeptides are simple isomers of each other, the lack of backbone chirality and hydrogen bonding in polypeptoids leads to surprisingly different surface behavior. Specifically, the polypeptoids surface segregate much more strongly than analogous polypeptide functionalized polymers, which in turn affects the performance of the coating. Indeed, polypeptoid functionalized surfaces were significantly better both in terms of anti-fouling and fouling release than the corresponding polypeptide-bearing polymers. The role of specific monomer sequence and backbone chemistry will be further discussed in this poster.

  13. Dissecting the relationship between protein structure and sequence variation

    NASA Astrophysics Data System (ADS)

    Shahmoradi, Amir; Wilke, Claus; Wilke Lab Team

    2015-03-01

    Over the past decade several independent works have shown that some structural properties of proteins are capable of predicting protein evolution. The strength and significance of these structure-sequence relations, however, appear to vary widely among different proteins, with absolute correlation strengths ranging from 0 . 1 to 0 . 8 . Here we present the results from a comprehensive search for the potential biophysical and structural determinants of protein evolution by studying more than 200 structural and evolutionary properties in a dataset of 209 monomeric enzymes. We discuss the main protein characteristics responsible for the general patterns of protein evolution, and identify sequence divergence as the main determinant of the strengths of virtually all structure-evolution relationships, explaining ~ 10 - 30 % of observed variation in sequence-structure relations. In addition to sequence divergence, we identify several protein structural properties that are moderately but significantly coupled with the strength of sequence-structure relations. In particular, proteins with more homogeneous back-bone hydrogen bond energies, large fractions of helical secondary structures and low fraction of beta sheets tend to have the strongest sequence-structure relation. BEACON-NSF center for the study of evolution in action.

  14. Influence of the polymer backbone structure on the properties of aromatic ionomers with pendant sulfobenzoyl side chains for use as proton-exchange membranes.

    PubMed

    Jutemar, Elin Persson; Jannasch, Patric

    2010-12-01

    Six different ionomers having various aromatic polymer backbones with pendant 2-sulfobenzoyl side chains were prepared by nucleophilic aromatic substitution reactions of lithium 2,6-difluoro-2'-sulfobenzophenone with 4,4-biphenol, 2,7-dihydroxynaphthalene, 4,4-isopropylidenediphenol, 4,4-dihydroxydiphenyl ether, 4,4'-thiodiphenol, and 4,4'-thiobisbenzenethiol, respectively, to produce four poly(arylene ether)s, one poly(arylene ether sulfide), and one poly(arylene sulfide). Mechanically tough proton-exchange membranes with ion-exchange capacities in the narrow range from 1.9 to 2.3 mequiv/g were cast from the high-molecular-weight ionomers, and subsequently investigated with respect to their structure-property relationships. Glass transitions were only detected for ionomers in the sodium salt form, and increasing glass-transition temperatures (Tg) were found to give higher thermal decomposition temperatures. Analysis by small-angle X-ray scattering indicated that the ionic clustering was promoted for ionomers with flexible polymer backbones and low Tg values. The proton conductivity of the membranes at 80 °C under fully humidified conditions was found between 0.02 and 0.2 S/cm and appeared to depend primarily on the Tg. PMID:21138250

  15. Structure Elucidation of Poly-Faldaprevir: Polymer Backbone Solved Using Solid-State and Solution Nuclear Magnetic Resonance Spectroscopy.

    PubMed

    Gonnella, Nina C; Busacca, Carl A; Zhang, Li; Saha, Anjan; Wu, Jiang-Ping; Li, Guisheng; Davis, Mark; Offerdahl, Thomas; Jones, Paul-James; Herfurth, Lars; Reddig, Tim; Wagner, Klaus; Niemann, Michael; Werthmann, Ulrike; Grupe, Julia; Roos, Helmut; Reckzügel, Gaby; Ding, Andreas

    2016-06-01

    A large-scale synthesis of the hepatitis C virus drug Faldaprevir revealed precipitation of an unknown insoluble solid from methanol solutions of the drug substance. The unknown impurity was determined to be a polymer of Faldaprevir based on analytical methods that included size exclusion chromatography in combination with electrospray ionization mass spectrometry, solution nuclear magnetic resonance (NMR), matrix-assisted laser desorption ionization-time of flight, ultracentrifugation, elemental analysis, and sodium quantitation by atom absorption spectroscopy. Structure elucidation of the polymeric backbone was achieved using solid-state NMR cross-polarization/magic angle spinning (CP/MAS), cross polarization-polarization inversion, and heteronuclear correlation (HETCOR) experiments. The polymerization was found to occur at the vinyl cyclopropane via a likely free radical initiation mechanism. Full proton and carbon chemical shift assignments of the polymer were obtained using solution NMR spectroscopy. The polymer structure was corroborated with chemical synthesis of the polymer and solution NMR analysis. PMID:27238486

  16. The structure of irregular mesospheric variations.

    NASA Technical Reports Server (NTRS)

    Justus, C. G.

    1972-01-01

    The daily difference method developed by Woodrum and Justus (1968) has been used to analyze the existing data in the height range from 50 to 200 km for irregular variations which could be due to gravity waves. The results presented establish the magnitude as well as the vertical and latitudinal structure of the irregular atmospheric variations. It is pointed out that results obtained by Theon et al. (1969) indicate strong seasonal variation in the magnitude of upper atmospheric waves at high latitudes.

  17. Structure variations of pumpkin balloon

    NASA Astrophysics Data System (ADS)

    Yajima, N.; Izutsu, N.; Honda, H.

    2004-01-01

    A lobed pumpkin balloon by 3-D gore design concept is recognized as a basic form for a super-pressure balloon. This paper deals with extensions of this design concept for other large pressurized membrane structures, such as a stratospheric airship and a balloon of which volume is controllable. The structural modifications are performed by means of additional ropes, belts or a strut. When the original pumpkin shape is modified by these systems, the superior characteristics of the 3-D gore design, incorporating large bulges with a small local radius and unidirectional film tension, should be maintained. Improved design methods which are adequate for the above subjects will be discussed in detail. Application for ground structures are also mentioned.

  18. Structure variations of pumpkin balloon

    NASA Astrophysics Data System (ADS)

    Yajima, N.; Izutsu, N.; Honda, H.

    A robed pumpkin balloon by 3-D gore design concept is recognized as a basic form for a super -pressure balloon. This paper deals with an extension of this design concept for other large pressurized membrane structures, such as a stratospheric airship and a balloon of which volume is controllable. The structural modifications are performed by means of additional ropes or poles. When the original pumpkin shape is modified for those systems, superior characteristics of 3-D gore design, those are large bulges with a small local radius and unidirectional film tension, should be maintained. Improved design methods which are adequate for the above subjects will be discussed in detail.

  19. Structural variations in plant genomes

    PubMed Central

    Edwards, David; Varshney, Rajeev K.

    2014-01-01

    Differences between plant genomes range from single nucleotide polymorphisms to large-scale duplications, deletions and rearrangements. The large polymorphisms are termed structural variants (SVs). SVs have received significant attention in human genetics and were found to be responsible for various chronic diseases. However, little effort has been directed towards understanding the role of SVs in plants. Many recent advances in plant genetics have resulted from improvements in high-resolution technologies for measuring SVs, including microarray-based techniques, and more recently, high-throughput DNA sequencing. In this review we describe recent reports of SV in plants and describe the genomic technologies currently used to measure these SVs. PMID:24907366

  20. "Pinning strategy": a novel approach for predicting the backbone structure in terms of protein blocks from sequence.

    PubMed

    De Brevern, A G; Etchebest, C; Benros, C; Hazout, S

    2007-01-01

    The description of protein 3D structures can be performed through a library of 3D fragments, named a structural alphabet. Our structural alphabet is composed of 16 small protein fragments of 5 C alpha in length, called protein blocks (PBs). It allows an efficient approximation of the 3D protein structures and a correct prediction of the local structure. The 72 most frequent series of 5 consecutive PBs, called structural words (SWs)are able to cover more than 90% of the 3D structures. PBs are highly conditioned by the presence of a limited number of transitions between them. In this study, we propose a new method called "pinning strategy" that used this specific feature to predict long protein fragments. Its goal is to define highly probable successions of PBs. It starts from the most probable SW and is then extended with overlapping SWs. Starting from an initial prediction rate of 34.4%, the use of the SWs instead of the PBs allows a gain of 4.5%. The pinning strategy simply applied to the SWs increases the prediction accuracy to 39.9%. In a second step, the sequence-structure relationship is optimized, the prediction accuracy reaches 43.6%. PMID:17426380

  1. Structural insights into the evolution of a sexy protein: novel topology and restricted backbone flexibility in a hypervariable pheromone from the red-legged salamander, Plethodon shermani.

    PubMed

    Wilburn, Damien B; Bowen, Kathleen E; Doty, Kari A; Arumugam, Sengodagounder; Lane, Andrew N; Feldhoff, Pamela W; Feldhoff, Richard C

    2014-01-01

    In response to pervasive sexual selection, protein sex pheromones often display rapid mutation and accelerated evolution of corresponding gene sequences. For proteins, the general dogma is that structure is maintained even as sequence or function may rapidly change. This phenomenon is well exemplified by the three-finger protein (TFP) superfamily: a diverse class of vertebrate proteins co-opted for many biological functions - such as components of snake venoms, regulators of the complement system, and coordinators of amphibian limb regeneration. All of the >200 structurally characterized TFPs adopt the namesake "three-finger" topology. In male red-legged salamanders, the TFP pheromone Plethodontid Modulating Factor (PMF) is a hypervariable protein such that, through extensive gene duplication and pervasive sexual selection, individual male salamanders express more than 30 unique isoforms. However, it remained unclear how this accelerated evolution affected the protein structure of PMF. Using LC/MS-MS and multidimensional NMR, we report the 3D structure of the most abundant PMF isoform, PMF-G. The high resolution structural ensemble revealed a highly modified TFP structure, including a unique disulfide bonding pattern and loss of secondary structure, that define a novel protein topology with greater backbone flexibility in the third peptide finger. Sequence comparison, models of molecular evolution, and homology modeling together support that this flexible third finger is the most rapidly evolving segment of PMF. Combined with PMF sequence hypervariability, this structural flexibility may enhance the plasticity of PMF as a chemical signal by permitting potentially thousands of structural conformers. We propose that the flexible third finger plays a critical role in PMF:receptor interactions. As female receptors co-evolve, this flexibility may allow PMF to still bind its receptor(s) without the immediate need for complementary mutations. Consequently, this unique

  2. Structural and dynamic implications of an effector-induced backbone amide cis-trans isomerization in cytochrome P450cam

    PubMed Central

    Asciutto, Eliana K.; Madura, Jeffry D.; Pochapsky, Susan Sondej; OuYang, Bo; Pochapsky, Thomas C.

    2009-01-01

    Experimental evidence has been provided for a functionally relevant cis-trans isomerization of the Ile 88-Pro 89 peptide bond in cytochrome P450cam (CYP101). The isomerization is proposed to be a key element of the structural reorganization leading to the catalytically competent form of CYP101 upon binding of the effector protein putidaredoxin (Pdx). A detailed comparison of the results of molecular dynamics simulations on the cis and trans conformations of substrate- and carbonmonoxy-bound ferrous CYP101 with sequence-specific Pdx-induced structural perturbations identified by nuclear magnetic resonance is presented, providing insight into the structural and dynamic consequences of the isomerization. The mechanical coupling between the Pdx binding site on the proximal face of CYP101 and the site of isomerization is described. PMID:19327368

  3. Structural and dynamic implications of an effector-induced backbone amide cis-trans isomerization in cytochrome P450cam.

    PubMed

    Asciutto, Eliana K; Madura, Jeffry D; Pochapsky, Susan Sondej; OuYang, Bo; Pochapsky, Thomas C

    2009-05-15

    Experimental evidence has been provided for a functionally relevant cis-trans isomerization of the Ile88-Pro89 peptide bond in cytochrome P450(cam) (CYP101). The isomerization is proposed to be a key element of the structural reorganization leading to the catalytically competent form of CYP101 upon binding of the effector protein putidaredoxin (Pdx). A detailed comparison of the results of molecular dynamics simulations on the cis and trans conformations of substrate- and carbonmonoxy-bound ferrous CYP101 with sequence-specific Pdx-induced structural perturbations identified by nuclear magnetic resonance is presented, providing insight into the structural and dynamic consequences of the isomerization. The mechanical coupling between the Pdx binding site on the proximal face of CYP101 and the site of isomerization is described. PMID:19327368

  4. Solution structure and backbone dynamics of an antigen-free heavy chain variable domain (VHH) from Llama.

    PubMed

    Renisio, Jean-Guillaume; Pérez, Janice; Czisch, Michael; Guenneugues, Marc; Bornet, Olivier; Frenken, Leon; Cambillau, Christian; Darbon, Hervé

    2002-06-01

    Camelids, (dromedaries, camels, and llamas) produce heavy-chains antibodies, with their antigen recognition sites composed of a single VH-like domain, referred to as VHH. The solution structure of one of these VHHs domains (VHH-H14), raised against the alpha subunit of the human chorionic gonadotropin hormone (hCG), has been determined by (15)N heteronuclear three-dimensional NMR spectroscopy. The framework is well resolved within the set of 20 best-calculated NMR structures and is close to that of classical VH domains from vertebrate antibodies, consisting of two antiparallel beta-sheets organized in a beta-barrel. Loops display a lower precision, especially the Complementarity Determining Regions (CDRs), involved in antigen recognition. Comparison of the three-dimensional VHH-H14 solution structure with its previously solved crystal structure (Spinelli et al., Nature Struct. Biol. 1996;3:752-757) reveals a high similarity to the framework, whereas significant conformational differences occur on CDRs, leading to the assumption that the antigen recognition site is a more mobile part. In order to deepen our insights into the dynamics of VHH-H14 in solution, (15)N relaxation was measured with longitudinal R1 and transverse R2 self-relaxation rates, and (15)N steady-state heteronuclear nuclear Overhauser enhancements (NOE), making it possible to probe picosecond-to-millisecond internal motions. Determination of dynamic parameters (S(2), tau(e), and Rex) through the Lipari-Szabo Model-free approach enables the identification of several regions with enhanced dynamics. Especially, the mobility measurements from NMR confirm that the antigen recognition site is the most mobile part of the VHH-H14 domain on picosecond-to-nanosecond fast time scales. Several residues belonging to the three CDRs are submitted to chemical exchange processes occurring on slow microsecond-to-millisecond time scales, suggesting that the formation of the VHH/antigen complex should be accompanied

  5. Drug screening strategy for human membrane proteins: from NMR protein backbone structure to in silica- and NMR-screened hits.

    PubMed

    Lindert, Steffen; Maslennikov, Innokentiy; Chiu, Ellis J C; Pierce, Levi C; McCammon, J Andrew; Choe, Senyon

    2014-03-21

    About 8000 genes encode membrane proteins in the human genome. The information about their druggability will be very useful to facilitate drug discovery and development. The main problem, however, consists of limited structural and functional information about these proteins because they are difficult to produce biochemically and to study. In this paper we describe the strategy that combines Cell-free protein expression, NMR spectroscopy, and molecular DYnamics simulation (CNDY) techniques. Results of a pilot CNDY experiment provide us with a guiding light towards expedited identification of the hit compounds against a new uncharacterized membrane protein as a potentially druggable target. These hits can then be further characterized and optimized to develop the initial lead compound quicker. We illustrate such "omics" approach for drug discovery with the CNDY strategy applied to two example proteins: hypoxia-induced genes HIGD1A and HIGD1B. PMID:24525125

  6. TMAO influence on the backbone of proteins: an oligoglycine model

    PubMed Central

    Hu, Char Y.; Lynch, Gillian C.; Kokubo, Hironori; Pettitt, B. Montgomery

    2009-01-01

    The study of organic osmolytes has been pivotal in demonstrating the role of solvent effects on the protein backbone in the folding process. Whereas a thermodynamic description of the interactions between the protein backbone and osmolyte has been well defined, the structural analysis of the effect of osmolyte on the protein backbone has been incomplete. Therefore, we have carried out simulations of a peptide backbone model, glycine15 in protecting osmolyte TMAO solution in order to determine the effect of the solution structure on the conformation of the peptide backbone. We demonstrate that the models chosen show that the ensemble of backbone structures shifts towards a more collapsed state in TMAO solution as compared to pure water solution. The collapse is consistent with preferential exclusion of the osmolyte caused by unfavorable interactions between osmolyte and peptide backbone. The exclusion is due to strong triplet correlations of osmolyte, water, and peptide backbone. This provides a clear mechanism demonstrating that even a modest concentration of TMAO forces the protein backbone to adopt a more collapsed structure in the absence of sidechain effects. PMID:19790265

  7. Solution structure and backbone dynamics of the DNA-binding domain of FOXP1: Insight into its domain swapping and DNA binding

    PubMed Central

    Chu, Yuan-Ping; Chang, Chia-Hao; Shiu, Jia-Hau; Chang, Yao-Tsung; Chen, Chiu-Yueh; Chuang, Woei-Jer

    2011-01-01

    FOXP1 belongs to the P-subfamily of forkhead transcription factors and contains a conserved forkhead DNA-binding domain. According to size exclusion chromatography analysis, the forkhead domain of FOXP1 existed as a mixture of monomer and dimer. The dissociation constants of the forkhead domain of wild-type, C61S, and C61Y mutants of FOXP1 were 27.3, 28.8, and 332.0 μM, respectively. In contrast, FOXP1 A39P mutant formed only a monomer. NMR analysis also showed that FOXP1 C61S and C61Y mutants existed as a mixture. The solution structure of FOXP1 A39P/C61Y mutant was similar to the X-ray structure of the FOXP2 monomer. Comparison of backbone dynamics of FOXP1 A39P/C61Y and C61Y mutants showed that the residues preceding helix 3, the hinge region, exhibited the largest conformational exchange in FOXP1 monomer. The A39 residue of FOXP1 dimer has a lower order parameter with internal motion on the ps-ns timescale, suggesting that the dynamics of the hinge region of FOXP1 are important in the formation of the swapped dimer. The analysis also showed that the residues exhibiting the motions on the ps-ns and μs-ms timescales were located at the DNA-binding surface of FOXP1, suggesting the interactions between FOXP1 and DNA may be highly dynamic. PMID:21416545

  8. Motor Task Variation Induces Structural Learning

    PubMed Central

    Braun, Daniel A.; Aertsen, Ad; Wolpert, Daniel M.; Mehring, Carsten

    2009-01-01

    Summary When we have learned a motor skill, such as cycling or ice-skating, we can rapidly generalize to novel tasks, such as motorcycling or rollerblading [1–8]. Such facilitation of learning could arise through two distinct mechanisms by which the motor system might adjust its control parameters. First, fast learning could simply be a consequence of the proximity of the original and final settings of the control parameters. Second, by structural learning [9–14], the motor system could constrain the parameter adjustments to conform to the control parameters' covariance structure. Thus, facilitation of learning would rely on the novel task parameters' lying on the structure of a lower-dimensional subspace that can be explored more efficiently. To test between these two hypotheses, we exposed subjects to randomly varying visuomotor tasks of fixed structure. Although such randomly varying tasks are thought to prevent learning, we show that when subsequently presented with novel tasks, subjects exhibit three key features of structural learning: facilitated learning of tasks with the same structure, strong reduction in interference normally observed when switching between tasks that require opposite control strategies, and preferential exploration along the learned structure. These results suggest that skill generalization relies on task variation and structural learning. PMID:19217296

  9. Solution structure of the ActD–5′-CCGTT3GTGG-3′ complex: drug interaction with tandem G·T mismatches and hairpin loop backbone

    PubMed Central

    Chin, Ko-Hsin; Chen, Fu-Ming; Chou, Shan-Ho

    2003-01-01

    Binding of actinomycin D (ActD) to the seemingly single-stranded DNA (ssDNA) oligomer 5′-CCGTT3 GTGG-3′ has been studied in solution using high-resolution nuclear magnetic resonance (NMR) techniques. A strong binding constant (8 × 106 M–1) and high quality NMR spectra have allowed us to determine the initial DNA structure using distance geometry as well as the final ActD–5′-CCGTT3 GTGG-3′ complex structure using constrained molecular dynamics calculations. The DNA oligomer 5′-CCGTT3GTGG-3′ in the complex forms a hairpin structure with tandem G·T mismatches at the stem region next to a loop of three stacked thymine bases pointing toward the major groove. Bipartite T2O–GH1 and T2O–G2NH2 hydrogen bonds were detected for the G·T mismatches that further stabilize this unusual DNA hairpin. The phenoxazone chromophore of ActD intercalates nicely between the tandem G·T mismatches in essentially one major orientation. Additional hydrophobic interactions between the ActD quinoid amino acid residues with the loop T5–T6–T7 backbone protons were also observed. The hydrophobic G–phenoxazone–G interaction in the ActD–5′-CCGTT3GTGG-3′ complex is more robust than that of the classical ActD– 5′-CCGCT3GCGG-3′ complex, consistent with the roughly 2-fold stronger binding of ActD to the 5′-CCGTT3GTGG-3′ sequence than to its 5′-CCG CT3GCGG-3′ counterpart. Stabilization by ActD of a hairpin containing non-canonical stem base pairs further strengthens the notion that ActD or other related compounds may serve as a sequence- specific ssDNA-binding agent that inhibits human immunodeficiency virus (HIV) and other retroviruses replicating through ssDNA intermediates. PMID:12736312

  10. Variational approach for static mirror structures

    SciTech Connect

    Kuznetsov, E. A.; Passot, T.; Sulem, P. L.; Ruban, V. P.

    2015-04-15

    Anisotropic static plasma equilibria where the parallel and perpendicular pressures are only functions of the amplitude of the local magnetic field are shown to be amenable to a variational principle with a free energy density given by the parallel tension. This approach is used to demonstrate that two-dimensional small-amplitude static magnetic holes constructed from a Grad-Shafranov type equation slightly below the (subcritical) mirror instability threshold identify with lump solitons of KPII equation, but turn out to be unstable. Differently, large-amplitude magnetic structures, which are stable as they realize a minimum of the free energy, are computed using a gradient method within two-dimensional numerical simulations where the regularizing effect of finite Larmor radius corrections is retained. Interestingly, these structures transform from stripes to bubbles when the angle of the magnetic field with the coordinate plane is increased.

  11. Reconstruction of protein backbones from the BriX collection of canonical protein fragments.

    PubMed

    Baeten, Lies; Reumers, Joke; Tur, Vicente; Stricher, François; Lenaerts, Tom; Serrano, Luis; Rousseau, Frederic; Schymkowitz, Joost

    2008-05-01

    As modeling of changes in backbone conformation still lacks a computationally efficient solution, we developed a discretisation of the conformational states accessible to the protein backbone similar to the successful rotamer approach in side chains. The BriX fragment database, consisting of fragments from 4 to 14 residues long, was realized through identification of recurrent backbone fragments from a non-redundant set of high-resolution protein structures. BriX contains an alphabet of more than 1,000 frequently observed conformations per peptide length for 6 different variation levels. Analysis of the performance of BriX revealed an average structural coverage of protein structures of more than 99% within a root mean square distance (RMSD) of 1 Angstrom. Globally, we are able to reconstruct protein structures with an average accuracy of 0.48 Angstrom RMSD. As expected, regular structures are well covered, but, interestingly, many loop regions that appear irregular at first glance are also found to form a recurrent structural motif, albeit with lower frequency of occurrence than regular secondary structures. Larger loop regions could be completely reconstructed from smaller recurrent elements, between 4 and 8 residues long. Finally, we observed that a significant amount of short sequences tend to display strong structural ambiguity between alpha helix and extended conformations. When the sequence length increases, this so-called sequence plasticity is no longer observed, illustrating the context dependency of polypeptide structures. PMID:18483555

  12. Mechanical reliability of porous low-k dielectrics for advanced interconnect: Study of the instability mechanisms in porous low-k dielectrics and their mediation through inert plasma induced re-polymerization of the backbone structure

    NASA Astrophysics Data System (ADS)

    Sa, Yoonki

    Continuous scaling down of critical dimensions in interconnect structures requires the use of ultralow dielectric constant (k) films as interlayer dielectrics to reduce resistance-capacitance delays. Porous carbon-doped silicon oxide (p-SiCOH) dielectrics have been the leading approach to produce these ultralow-k materials. However, embedding of porosity into dielectric layer necessarily decreases the mechanical reliability and increases its susceptibility to adsorption of potentially deleterious chemical species during device fabrication process. Among those, exposure of porous-SiCOH low-k (PLK) dielectrics to oxidizing plasma environment causes the increase in dielectric constant and their vulnerability to mechanical instability of PLKs due to the loss of methyl species and increase in moisture uptake. These changes in PLK properties and physical stability have been persisting challenges for next-generation interconnects because they are the sources of failure in interconnect integration as well as functional and physical failures appearing later in IC device manufacturing. It is therefore essential to study the fundamentals of the interactions on p-SiCOH matrix induced by plasma exposure and find an effective and easy-to-implement way to reverse such changes by repairing damage in PLK structure. From these perspectives, the present dissertation proposes 1) a fundamental understanding of structural transformation occurring during oxidative plasma exposure in PLK matrix structure and 2) its restoration by using silylating treatment, soft x-ray and inert Ar-plasma radiation, respectively. Equally important, 3) as an alternative way of increasing the thermo-mechanical reliability, PLK dielectric film with an intrinsically robust structure by controlling pore morphology is fabricated and investigated. Based on the investigations, stability of PLK films studied by time-dependent ball indentation tester under the elevated temperature, variation in film thickness and

  13. The "universal polymer backbone" concept

    NASA Astrophysics Data System (ADS)

    Pollino, Joel Matthew

    This thesis begins with a brief analysis of the synthetic methodologies utilized in polymer science. A conclusion is drawn inferring that upper limits in molecular design are inevitable, arising as a direct consequence of the predominance of covalent strategies in the field. To address these concerns, the 'universal polymer backbone' (UPB) concept has been hypothesized. A UPB has been defined as any copolymer, side-chain functionalized with multiple recognition elements that are individually capable of forming strong, directional, and reversible non-covalent bonds. Non-covalent functionalization of these scaffolds can lead to the formation of a multitude of new polymer structures, each stemming from a single parent or 'universal polymer backbone'. To prepare such a UPB, isomerically pure exo-norbornene esters containing either a PdII SCS pincer complex or a diaminopyridine residue were synthesized, polymerized, and copolymerized via ROMP. All polymerizations were living under mild reaction conditions. Kinetic studies showed that the kp values are highly dependent upon the isomeric purity but completely independent of the terminal recognition units. Non-covalent functionalization of these copolymers was accomplished via (1) directed self-assembly, (2) multi-step self-assembly , and (3) one-step orthogonal self-assembly. This system shows complete specificity of each recognition motif for its complementary unit with no observable changes in the association constant upon functionalization. To explore potential applications of this UPB concept, random terpolymers possessing high concentrations of pendant alkyl chains and small amounts of recognition units were synthesized. Non-covalent crosslinking using a directed functionalization strategy resulted in dramatic increases in solution viscosities for metal crosslinked polymers with only minor changes in viscosity for hydrogen bonding motifs. The crosslinked materials were further functionalized via self-assembly by

  14. Variational modeling of ionic polymer plate structures

    NASA Astrophysics Data System (ADS)

    Buechler, Miles A.; Leo, Donald J.

    2006-03-01

    Ionomeric polymers are a promising class of intelligent material which exhibit electromechanical coupling similar to that of piezoelectric bimorphs. Ionomeric polymers are much more compliant than piezoelectric ceramics or polymers and have been shown to produce actuation strain on the order of 5% at operating voltages between 1 V and 5 V. This performance indicates the potential for self-actuating devices manufactured from ionomeric polymers, such as deformable mirrors or low pressure pump diaphragms. This paper presents a variational approach to the dynamic modeling of ionic polymer plates in rectangular coordinates. A linear matrix equation, which relates displacement and charge to applied forces and voltage, is developed to determine the response of the structure to applied forces and applied potentials. The modeling method is based on the incorporation of empirically determined material properties, which have been shown to be highly frequency dependent. The matrices are calculated at discrete frequencies and solved frequency-by-frequency to determine the response of the ionomeric plate structures. A model of a thin rectangular plate is developed and validated experimentally. Simulated frequency response functions are compared to experimental results for several locations on the plate. The response of the plate at certain frequencies is computed and compared to experimentally-determined response shapes. The results demonstrate the validity of the modeling approach in predicting the dynamic response of the ionomeric plate structure. These spatial solutions are also compared to experimentally determined response shapes.

  15. A sampling approach for protein backbone fragment conformations.

    PubMed

    Yu, J Y; Zhang, W

    2013-01-01

    In protein structure prediction, backbone fragment bias information can narrow down the conformational space of the whole polypeptide chain significantly. Unlike existing methods that use fragments as building blocks, the paper presents a probabilistic sampling approach for protein backbone torsion angles by modelling angular correlation of (phi, psi) with a directional statistics distribution. Given a protein sequence and secondary structure information, this method samples backbone fragments conformations by using a backtrack sampling algorithm for the hidden Markov model with multiple inputs and a single output. The proposed approach is applied to a fragment library, and some well-known structural motifs are sampled very well on the optimal path. Computational results show that the method can help to obtain native-like backbone fragments conformations. PMID:23777175

  16. Analysis of the Rotational Structure in the High-Resolution Infrared Spectrum of trans-Hexatriene-1-13C1; a Semiexperimental Equilibrium Structure for the C6 Backbone for trans-Hexatriene

    SciTech Connect

    Craig, Norman C.; Tian, Hengfeng; Blake, Thomas A.

    2012-03-29

    trans-Hexatriene-1-13C1 (tHTE-1-13C1) has been synthesized, and its high-resolution (0.0015 cm-1) infrared spectrum has been recorded. The rotational structure in the C-type bands for v26 at 1011 cm-1 and v30 at 894 cm-1 has been analyzed. To the 1458 ground state combination differences from these bands, ground state rotational constants were fitted to a Watson-type Hamiltonian to give A0 = 0.8728202(9), B0 = 0.0435868(4), and C0 = 0.0415314(2) cm-1. Upper state rotational constants for the v30 band were also fitted. Predictions of the ground state rotational constants for t-HTE-1-13C1 from a B3LYP/cc-pVTZ model with scale factors based on the normal species were in excellent agreement with observations. Similar good agreement was found between predicted and observed ground state rotational constants for the three 13C1 isotopologues of cis-hexatriene (cHTE), as determined from microwave spectroscopy. Equilibrium rotational constants for tHTE and its three 13C1 isotopologues, of which two were predicted, were used to find a semiexperimental equilibrium structure for the C6 backbone of tHTE. This structure shows increased structural effects of pi-electron delocalization in comparison with butadiene.

  17. ANSS Backbone Station Installation and Site Characterization

    NASA Astrophysics Data System (ADS)

    Meremonte, M.; Leeds, A.; Overturf, D.; McMillian, J.; Allen, J.; McNamara, D.

    2004-12-01

    During 2004 several new broadband seismic stations have been deployed as a part of the USGS's Advanced National Seismic System (ANSS) backbone and regional networks. New stations include: ERPA, MNTX, OGLA, AMTX, NATX, KCCO, BMO, MARC, TZTN, LAO, DGMT, REDW, KSU1, MOOW, TPAW, LOHW, RAMW. Permanent station locations were chosen to minimize the local noise conditions by recording continuous data and using a quantitative analysis of the statistical distribution of noise power estimates. For each one-hour segment of continuous data, a power spectral density (PSD) is estimated and smoothed in full octave averages at 1/8 octave intervals. Powers for each 1/8 period interval were then accumulated in one dB power bins. A statistical analysis of power bins yields probability density functions (PDFs) as a function of noise power for each of the octave bands at each station and component. Examination of earthquake signal, artifacts related to station operation and episodic cultural noise in the PDFs allow us to estimate both the overall station quality and the level of earth noise at each potential backbone site. The main function of a seismic network, such as the ANSS, is to provide high quality data for earthquake monitoring, source studies, and Earth structure research. The utility of seismic data is greatly increased when noise levels are reduced. A good quantification and understanding of seismic noise is a first step at reducing noise levels in seismic data and improving overall data quality from the ANSS backbone network.

  18. Simulation of Ames Backbone Network

    NASA Technical Reports Server (NTRS)

    Shahnasser, Hamid

    1998-01-01

    The networking demands of Ames Research Center are dramatically increasing. More and more workstations are requested to run video and audio applications on the network. These applications require a much greater bandwidth than data applications. The existing ARCLAN 2000 network bandwidth is insufficient, due to the use of FDDI as its backbone, for accommodating video applications. Operating at a maximum of 100 Mbps, FDDI can handle only a few workstations running multimedia applications. The ideal solution is to replace the current ARCLAN 2000 FDDI backbone with an ATM backbone. ATM has the capability to handle the increasing traffic loads on the ARCLAN 2000 that results from these new applications. As it can be seen from Figure 1, ARCLAN 2000 have a total of 32 routers (5 being core routers) each connected to the FDDI backbone via a 100 Mbps link. This network serves 34 different locations by using 34 hubs that are connected to secondary routers. End users are connected to the secondary routers with 10 Mbps links.

  19. Large-scale measurement and modeling of backbone Internet traffic

    NASA Astrophysics Data System (ADS)

    Roughan, Matthew; Gottlieb, Joel

    2002-07-01

    There is a brewing controversy in the traffic modeling community concerning how to model backbone traffic. The fundamental work on self-similarity in data traffic appears to be contradicted by recent findings that suggest that backbone traffic is smooth. The traffic analysis work to date has focused on high-quality but limited-scope packet trace measurements; this limits its applicability to high-speed backbone traffic. This paper uses more than one year's worth of SNMP traffic data covering an entire Tier 1 ISP backbone to address the question of how backbone network traffic should be modeled. Although the limitations of SNMP measurements do not permit us to comment on the fine timescale behavior of the traffic, careful analysis of the data suggests that irrespective of the variation at fine timescales, we can construct a simple traffic model that captures key features of the observed traffic. Furthermore, the model's parameters are measurable using existing network infrastructure, making this model practical in a present-day operational network. In addition to its practicality, the model verifies basic statistical multiplexing results, and thus sheds deep insight into how smooth backbone traffic really is.

  20. Mechanical reliability of porous low-k dielectrics for advanced interconnect: Study of the instability mechanisms in porous low-k dielectrics and their mediation through inert plasma induced re-polymerization of the backbone structure

    NASA Astrophysics Data System (ADS)

    Sa, Yoonki

    Continuous scaling down of critical dimensions in interconnect structures requires the use of ultralow dielectric constant (k) films as interlayer dielectrics to reduce resistance-capacitance delays. Porous carbon-doped silicon oxide (p-SiCOH) dielectrics have been the leading approach to produce these ultralow-k materials. However, embedding of porosity into dielectric layer necessarily decreases the mechanical reliability and increases its susceptibility to adsorption of potentially deleterious chemical species during device fabrication process. Among those, exposure of porous-SiCOH low-k (PLK) dielectrics to oxidizing plasma environment causes the increase in dielectric constant and their vulnerability to mechanical instability of PLKs due to the loss of methyl species and increase in moisture uptake. These changes in PLK properties and physical stability have been persisting challenges for next-generation interconnects because they are the sources of failure in interconnect integration as well as functional and physical failures appearing later in IC device manufacturing. It is therefore essential to study the fundamentals of the interactions on p-SiCOH matrix induced by plasma exposure and find an effective and easy-to-implement way to reverse such changes by repairing damage in PLK structure. From these perspectives, the present dissertation proposes 1) a fundamental understanding of structural transformation occurring during oxidative plasma exposure in PLK matrix structure and 2) its restoration by using silylating treatment, soft x-ray and inert Ar-plasma radiation, respectively. Equally important, 3) as an alternative way of increasing the thermo-mechanical reliability, PLK dielectric film with an intrinsically robust structure by controlling pore morphology is fabricated and investigated. Based on the investigations, stability of PLK films studied by time-dependent ball indentation tester under the elevated temperature, variation in film thickness and

  1. An approach to the structure determination of nucleic acid analogues hybridized to RNA. NMR studies of a duplex between 2'-OMe RNA and an oligonucleotide containing a single amide backbone modification.

    PubMed Central

    Blommers, M J; Pieles, U; De Mesmaeker, A

    1994-01-01

    The backbone modification amide-3, in which -CH2-NH-CO-CH2- replaces -C5'H2-O5'-PO2-O3'-, is studied in the duplex d(G1-C2-G3-T4.T5-G6-C7-G8)*mr(C9-G10-C11-A12-A13-C14-G15+ ++-C16) where . indicates the backbone modification and mr indicates the 2'-OMe RNA strand. The majority of the exchangeable and non-exchangeable resonances have been assigned. The assignment procedure differs from standard methods. The methyl substituent of the 2'-OMe position of the RNA strand can be used as a tool in the interpretation. The duplex structure is a right-handed double helix. The sugar conformations of the 2'-OMe RNA strand are predominantly N-type and the 2'-OMe is positioned at the surface of the minor groove. In the complementary strand, only the sugar of residue T4 is found exclusively in N-type conformation. The incorporation of the amide modification does not effect very strongly the duplex structure. All bases are involved in Watson-Crick base pairs. PMID:7524037

  2. Child Development and Structural Variation in the Human Genome

    ERIC Educational Resources Information Center

    Zhang, Ying; Haraksingh, Rajini; Grubert, Fabian; Abyzov, Alexej; Gerstein, Mark; Weissman, Sherman; Urban, Alexander E.

    2013-01-01

    Structural variation of the human genome sequence is the insertion, deletion, or rearrangement of stretches of DNA sequence sized from around 1,000 to millions of base pairs. Over the past few years, structural variation has been shown to be far more common in human genomes than previously thought. Very little is currently known about the effects…

  3. ANSS Backbone Station Quality Assessment

    NASA Astrophysics Data System (ADS)

    Leeds, A.; McNamara, D.; Benz, H.; Gee, L.

    2006-12-01

    In this study we assess the ambient noise levels of the broadband seismic stations within the United States Geological Survey's (USGS) Advanced National Seismic System (ANSS) backbone network. The backbone consists of stations operated by the USGS as well as several regional network stations operated by universities. We also assess the improved detection capability of the network due to the installation of 13 additional backbone stations and the upgrade of 26 existing stations funded by the Earthscope initiative. This assessment makes use of probability density functions (PDF) of power spectral densities (PSD) (after McNamara and Buland, 2004) computed by a continuous noise monitoring system developed by the USGS- ANSS and the Incorporated Research Institutions in Seismology (IRIS) Data Management Center (DMC). We compute the median and mode of the PDF distribution and rank the stations relative to the Peterson Low noise model (LNM) (Peterson, 1993) for 11 different period bands. The power of the method lies in the fact that there is no need to screen the data for system transients, earthquakes or general data artifacts since they map into a background probability level. Previous studies have shown that most regional stations, instrumented with short period or extended short period instruments, have a higher noise level in all period bands while stations in the US network have lower noise levels at short periods (0.0625-8.0 seconds), high frequencies (8.0- 0.125Hz). The overall network is evaluated with respect to accomplishing the design goals set for the USArray/ANSS backbone project which were intended to increase broadband performance for the national monitoring network.

  4. Self-assembly of diphenylalanine backbone homologues and their combination with functionalized carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Dinesh, Bhimareddy; Squillaci, Marco A.; Ménard-Moyon, Cécilia; Samorì, Paolo; Bianco, Alberto

    2015-09-01

    The integration of carbon nanotubes (CNTs) into organized nanostructures is of great interest for applications in materials science and biomedicine. In this work we studied the self-assembly of β and γ homologues of diphenylalanine peptides under different solvent and pH conditions. We aimed to investigate the role of peptide backbone in tuning the formation of different types of nanostructures alone or in combination with carbon nanotubes. In spite of having the same side chain, β and γ peptides formed distinctively different nanofibers, a clear indication of the role played by the backbone homologation on the self-assembly. The variation of the pH allowed to transform the nanofibers into spherical structures. Moreover, the co-assembly of β and γ peptides with carbon nanotubes covalently functionalized with the same peptide generated unique dendritic assemblies. This comparative study on self-assembly using diphenylalanine backbone homologues and of the co-assembly with CNT covalent conjugates is the first example exploring the capacity of β and γ peptides to adopt precise nanostructures, particularly in combination with carbon nanotubes. The dendritic organization obtained by mixing carbon nanotubes and peptides might find interesting applications in tissue engineering and neuronal interfacing.The integration of carbon nanotubes (CNTs) into organized nanostructures is of great interest for applications in materials science and biomedicine. In this work we studied the self-assembly of β and γ homologues of diphenylalanine peptides under different solvent and pH conditions. We aimed to investigate the role of peptide backbone in tuning the formation of different types of nanostructures alone or in combination with carbon nanotubes. In spite of having the same side chain, β and γ peptides formed distinctively different nanofibers, a clear indication of the role played by the backbone homologation on the self-assembly. The variation of the pH allowed to

  5. Backbone upgrades and DEC equipment replacement

    NASA Technical Reports Server (NTRS)

    Vancamp, Warren

    1991-01-01

    The NASA Science Internet (NSI) dual protocol backbone is outlined. It includes DECnet link upgrades to match TCP/IP link performance. It also includes the integration of backbone resources and central management. The phase 1 transition process is outlined.

  6. Secondary Structure, Backbone Dynamics, and Structural Topology of Phospholamban and Its Phosphorylated and Arg9Cys-Mutated Forms in Phospholipid Bilayers Utilizing 13C and 15N Solid-State NMR Spectroscopy

    PubMed Central

    2015-01-01

    Phospholamban (PLB) is a membrane protein that regulates heart muscle relaxation rates via interactions with the sarcoplasmic reticulum Ca2+ ATPase (SERCA). When PLB is phosphorylated or Arg9Cys (R9C) is mutated, inhibition of SERCA is relieved. 13C and 15N solid-state NMR spectroscopy is utilized to investigate conformational changes of PLB upon phosphorylation and R9C mutation. 13C=O NMR spectra of the cytoplasmic domain reveal two α-helical structural components with population changes upon phosphorylation and R9C mutation. The appearance of an unstructured component is observed on domain Ib. 15N NMR spectra indicate an increase in backbone dynamics of the cytoplasmic domain. Wild-type PLB (WT-PLB), Ser16-phosphorylated PLB (P-PLB), and R9C-mutated PLB (R9C-PLB) all have a very dynamic domain Ib, and the transmembrane domain has an immobile component. 15N NMR spectra indicate that the cytoplasmic domain of R9C-PLB adopts an orientation similar to P-PLB and shifts away from the membrane surface. Domain Ib (Leu28) of P-PLB and R9C-PLB loses the alignment. The R9C-PLB adopts a conformation similar to P-PLB with a population shift to a more extended and disordered state. The NMR data suggest the more extended and disordered forms of PLB may relate to inhibition relief. PMID:24511878

  7. Backbone Dynamics Of Intracellular Lipid Binding Proteins

    NASA Astrophysics Data System (ADS)

    Gutiérrez-González, Luis H.

    2005-04-01

    The family of intracellular lipid binding proteins (iLBPs) comprises a group of homologous 14-15 kDa proteins that specifically bind and facilitate the transport of fatty acids, bile acids, retinoids or eicosanoids. Members of this family include several types of fatty acid binding proteins (FABPs), ileal lipid binding protein, cellular retinoic acid binding proteins and cellular retinoid binding proteins. As a contribution to understanding the structure-function relationship in this protein family, the solution structure and backbone dynamics of human epidermal-type FABP (E-FABP) determined by NMR spectroscopy are reported. Moreover, hydrogen/deuterium exchange experiments indicated a direct correlation between the stability of the hydrogen-bonding network in the β-sheet structure and the conformational exchange in the millisecond-to-microsecond time range. The features of E-FABP backbone dynamics discussed in the present study are compared with those obtained for other phylogenetically related proteins. A strong interdependence with the overall protein stability and possibly also with the ligand-binding affinity for members of the lipid-binding protein family is shown.

  8. Constructing optimal backbone segments for joining fixed DNA base pairs.

    PubMed Central

    Mazur, J; Jernigan, R L; Sarai, A

    1996-01-01

    A method is presented to link a sequence of space-fixed base pairs by the sugar-phosphate segments of single nucleotides and to evaluate the effects in the backbone caused by this positioning of the bases. The entire computational unit comprises several nucleotides that are energy-minimized, subject to constraints imposed by the sugar-phosphate backbone segments being anchored to space-fixed base pairs. The minimization schemes are based on two stages, a conjugate gradient method followed by a Newton-Raphson algorithm. Because our purpose is to examine the response, or relaxation, of an artificially stressed backbone, it is essential to be able to obtain, as closely as possible, a lowest minimum energy conformation of the backbone segment in conformational space. For this purpose, an algorithm is developed that leads to the generation of an assembly of many local energy minima. From these sets of local minima, one conformation corresponding to the one with the lowest minimum is then selected and designated to represent the backbone segment at its minimum. The effective electrostatic potential of mean force is expressed in terms of adjustable parameters that incorporate solvent screening action in the Coulombic interactions between charged backbone atoms; these parameters are adjusted to obtain the best fit of the nearest-neighbor phosphorous atoms in an x-ray structure. PMID:8874023

  9. Backbone 1H, 15N, and 13C resonance assignments and secondary structure of a novel protein OGL-20P(T)-358 from hyperthermophile Thermococcus thioreducens sp. nov.

    PubMed

    Wilson, Randall; Hughes, Ronny; Curto, Ernest; Ng, Joseph; Twigg, Pamela

    2007-12-31

    OGL-20P(T)-358 is a novel 66 amino acid residue protein from the hyperthermophile Thermococcus thioreducens sp. nov., strain OGL-20PT, which was collected from the wall of the hydrothermal black smoker in the Rainbow Vent along the mid-Atlantic ridge. This protein, which has no detectable sequence homology with proteins or domains of known function, has a calculated pI of 4.76 and a molecular mass of 8.2 kDa. We report here the backbone 1H, 15N, and 13C resonance assignments of OGL-20PT-358. Assignments are 97.5% (316/324) complete. Chemical shift index was used to determine the secondary structure of the protein, which appears to consist of primarily alpha-helical regions. This work is the foundation for future studies to determine the three-dimensional solution structure of the protein. PMID:18182861

  10. Variations in the Circumplex Structure of Mood.

    ERIC Educational Resources Information Center

    Feldman, Lisa A.

    1995-01-01

    Researchers have emphasized the similarity of the semantic and self-report mood circumplexes. Study investigated systematic differences in theses structures. Demonstrated that when making judgments of their mood, people weigh the arousal dimension less than the valence dimension. Dimensions are weighed equally in semantic structure. (JBJ)

  11. Evolution of functional nucleic acids in the presence of nonheritable backbone heterogeneity

    PubMed Central

    Trevino, Simon G.; Zhang, Na; Elenko, Mark P.; Lupták, Andrej; Szostak, Jack W.

    2011-01-01

    Multiple lines of evidence support the hypothesis that the early evolution of life was dominated by RNA, which can both transfer information from generation to generation through replication directed by base-pairing, and carry out biochemical activities by folding into functional structures. To understand how life emerged from prebiotic chemistry we must therefore explain the steps that led to the emergence of the RNA world, and in particular, the synthesis of RNA. The generation of pools of highly pure ribonucleotides on the early Earth seems unlikely, but the presence of alternative nucleotides would support the assembly of nucleic acid polymers containing nonheritable backbone heterogeneity. We suggest that homogeneous monomers might not have been necessary if populations of heterogeneous nucleic acid molecules could evolve reproducible function. For such evolution to be possible, function would have to be maintained despite the repeated scrambling of backbone chemistry from generation to generation. We have tested this possibility in a simplified model system, by using a T7 RNA polymerase variant capable of transcribing nucleic acids that contain an approximately 1∶1 mixture of deoxy- and ribonucleotides. We readily isolated nucleotide-binding aptamers by utilizing an in vitro selection process that shuffles the order of deoxy- and ribonucleotides in each round. We describe two such RNA/DNA mosaic nucleic acid aptamers that specifically bind ATP and GTP, respectively. We conclude that nonheritable variations in nucleic acid backbone structure may not have posed an insurmountable barrier to the emergence of functionality in early nucleic acids. PMID:21825162

  12. Structure-activity study for (bis)ureidopropyl- and (bis)thioureidopropyldiamine LSD1 inhibitors with 3-5-3 and 3-6-3 carbon backbone architectures

    PubMed Central

    Nowotarski, Shannon L.; Pachaiyappan, Boobalan; Holshouser, Steven L.; Kutz, Craig J.; Li, Youxuan; Huang, Yi; Sharma, Shiv K.; Casero, Robert A.; Woster, Patrick M.

    2015-01-01

    Methylation at specific histone lysine residues is a critical post-translational modification that alters chromatin architecture, and dysregulated lysine methylation/demethylation is associated with the silencing of tumor suppressor genes. The enzyme lysine-specific demethylase 1 (LSD1) complexed to specific transcription factors catalyzes the oxidative demethylation of mono- and dimethyllysine 4 of histone H3 (H3K4me and H3K4me2 respectively). We have previously reported potent (bis)urea and (bis)thiourea LSD1 inhibitors that increase cellular levels of H3K4me and H3K4me2, promote the re-expression of silenced tumor suppressor genes and suppress tumor growth in vitro. Here we report the design additional (bis)urea and (bis)thiourea LSD1 inhibitors that feature 3-5-3 or 3-6-3 carbon backbone architectures. Three of these compounds displayed single-digit IC50 values in a recombinant LSD1 assay. In addition, compound 6d exhibited an IC50 of 4.2 μM against the Calu-6 human lung adenocarcinoma line, and 4.8 μM against the MCF7 breast tumor cell line, in an MTS cell viability assay. Following treatment with 6b–6d, Calu-6 cells exhibited a significant increase in the mRNA expression for the silenced tumor suppressor genes SFRP2, HCAD and p16, and modest increases in GATA4 message. The compounds described in this paper represent the most potent epigenetic modulators in this series, and have potential for use as antitumor agents. PMID:25725609

  13. Protein structure prediction from sequence variation

    PubMed Central

    Marks, Debora S; Hopf, Thomas A; Sander, Chris

    2015-01-01

    Genomic sequences contain rich evolutionary information about functional constraints on macromolecules such as proteins. This information can be efficiently mined to detect evolutionary couplings between residues in proteins and address the long-standing challenge to compute protein three-dimensional structures from amino acid sequences. Substantial progress has recently been made on this problem owing to the explosive growth in available sequences and the application of global statistical methods. In addition to three-dimensional structure, the improved understanding of covariation may help identify functional residues involved in ligand binding, protein-complex formation and conformational changes. We expect computation of covariation patterns to complement experimental structural biology in elucidating the full spectrum of protein structures, their functional interactions and evolutionary dynamics. PMID:23138306

  14. The backbone of a city

    NASA Astrophysics Data System (ADS)

    Scellato, S.; Cardillo, A.; Latora, V.; Porta, S.

    2006-03-01

    Recent studies have revealed the importance of centrality measures to analyze various spatial factors affecting human life in cities. Here we show how it is possible to extract the backbone of a city by deriving spanning trees based on edge betweenness and edge information. By using as sample cases the cities of Bologna and San Francisco, we show how the obtained trees are radically different from those based on edge lengths, and allow an extended comprehension of the “skeleton” of most important routes that so much affects pedestrian/vehicular flows, retail commerce vitality, land-use separation, urban crime and collective dynamical behaviours.

  15. Imaging crustal structure variation across southeastern Australia

    NASA Astrophysics Data System (ADS)

    Fontaine, Fabrice R.; Tkalčić, Hrvoje; Kennett, Brian L. N.

    2013-01-01

    A broad-band seismic network of 28 three-component seismometers was deployed in southeastern Australia to examine variations in crustal thickness across the transition between Precambrian and Phanerozoic lithosphere. Receiver function observations and modelling of P-to-S conversions at the Mohorovičić discontinuity (Moho) have been employed to investigate: (i) the variations in the Moho depth across southeastern Australia, and (ii) the nature of the transition between crust and mantle. Data from temporary deployments were used together with data from the few permanent broad-band stations in the region. The extraction of P-receiver functions from high-quality seismic data recorded on these stations has enabled the determination of the crustal thickness across the region. The crustal thicknesses lie in the range 28-48 km. The Moho depth is generally well correlated with the Earth surface elevation in the southeastern Australia. The Moho estimates from receiver functions are in good agreement with results from reflection profiling. The average crustal thickness is found to be around 39 km beneath the Precambrian area in the west and even thicker beneath the Lachlan Orogen in the east (~ 43 km). The average crustal thickness in between, beneath the Murray Basin is thinner ~ 32 km. Interestingly, the crust in the Mount Gambier volcanic area is rather thick ~ 41 km, suggesting that the limit between the Delamerian and western Lachlan orogens is located east of Mount Gambier. Our results favour a position for the Tasman Line generally consistent with the interpretation by Direen and Crawford (2003) and thus to the east of the location favoured by many authors. The broader crust-mantle transition and thicker crust beneath the Lachlan Orogen suggest the presence of magmatic underplating at the base of the lower crust. The intermediate nature of the crust-mantle transition also suggests magmatic underplating beneath the Gawler Craton and the Curnamona Province.

  16. Structural Variation in Bacterial Glyoxalase I Enzymes

    PubMed Central

    Suttisansanee, Uthaiwan; Lau, Kelvin; Lagishetty, Satyanarayana; Rao, Krishnamurthy N.; Swaminathan, Subramanyam; Sauder, J. Michael; Burley, Stephen K.; Honek, John F.

    2011-01-01

    The glyoxalase system catalyzes the conversion of toxic, metabolically produced α-ketoaldehydes, such as methylglyoxal, into their corresponding nontoxic 2-hydroxycarboxylic acids, leading to detoxification of these cellular metabolites. Previous studies on the first enzyme in the glyoxalase system, glyoxalase I (GlxI), from yeast, protozoa, animals, humans, plants, and Gram-negative bacteria, have suggested two metal activation classes, Zn2+ and non-Zn2+ activation. Here, we report a biochemical and structural investigation of the GlxI from Clostridium acetobutylicum, which is the first GlxI enzyme from Gram-positive bacteria that has been fully characterized as to its three-dimensional structure and its detailed metal specificity. It is a Ni2+/Co2+-activated enzyme, in which the active site geometry forms an octahedral coordination with one metal atom, two water molecules, and four metal-binding ligands, although its inactive Zn2+-bound form possesses a trigonal bipyramidal geometry with only one water molecule liganded to the metal center. This enzyme also possesses a unique dimeric molecular structure. Unlike other small homodimeric GlxI where two active sites are located at the dimeric interface, the C. acetobutylicum dimeric GlxI enzyme also forms two active sites but each within single subunits. Interestingly, even though this enzyme possesses a different dimeric structure from previously studied GlxI, its metal activation characteristics are consistent with properties of other GlxI. These findings indicate that metal activation profiles in this class of enzyme hold true across diverse quaternary structure arrangements. PMID:21914803

  17. Self-assembly of diphenylalanine backbone homologues and their combination with functionalized carbon nanotubes.

    PubMed

    Dinesh, Bhimareddy; Squillaci, Marco A; Ménard-Moyon, Cécilia; Samorì, Paolo; Bianco, Alberto

    2015-10-14

    The integration of carbon nanotubes (CNTs) into organized nanostructures is of great interest for applications in materials science and biomedicine. In this work we studied the self-assembly of β and γ homologues of diphenylalanine peptides under different solvent and pH conditions. We aimed to investigate the role of peptide backbone in tuning the formation of different types of nanostructures alone or in combination with carbon nanotubes. In spite of having the same side chain, β and γ peptides formed distinctively different nanofibers, a clear indication of the role played by the backbone homologation on the self-assembly. The variation of the pH allowed to transform the nanofibers into spherical structures. Moreover, the co-assembly of β and γ peptides with carbon nanotubes covalently functionalized with the same peptide generated unique dendritic assemblies. This comparative study on self-assembly using diphenylalanine backbone homologues and of the co-assembly with CNT covalent conjugates is the first example exploring the capacity of β and γ peptides to adopt precise nanostructures, particularly in combination with carbon nanotubes. The dendritic organization obtained by mixing carbon nanotubes and peptides might find interesting applications in tissue engineering and neuronal interfacing. PMID:26359907

  18. Genetic variation, predator–prey interactions and food web structure

    PubMed Central

    Moya-Laraño, Jordi

    2011-01-01

    Food webs are networks of species that feed on each other. The role that within-population phenotypic and genetic variation plays in food web structure is largely unknown. Here, I show via simulation how variation in two key traits, growth rates and phenology, by influencing the variability of body sizes present through time, can potentially affect several structural parameters in the direction of enhancing food web persistence: increased connectance, decreased interaction strengths, increased variation among interaction strengths and increased degree of omnivory. I discuss other relevant traits whose variation could affect the structure of food webs, such as morphological and additional life-history traits, as well as animal personalities. Furthermore, trait variation could also contribute to the stability of food web modules through metacommunity dynamics. I propose future research to help establish a link between within-population variation and food web structure. If appropriately established, such a link could have important consequences for biological conservation, as it would imply that preserving (functional) genetic variation within populations could ensure the preservation of entire communities. PMID:21444316

  19. Peptide Amphiphile Nanofibers with Conjugated Polydiacetylene Backbones in Their Core

    PubMed Central

    Hsu, Lorraine; Cvetanovich, Gregory L.; Stupp, Samuel I.

    2008-01-01

    The coupling of electronic and biological functionality through self-assembly is an interesting target in supramolecular chemistry. We report here on a set of diacetylene-derivatized peptide amphiphiles (PAs) that react to form conjugated polydiacetylene backbones following self-assembly into cylindrical nanofibers. The polymerization reaction yields highly conjugated backbones when the peptidic segment of the PAs has a linear, as opposed to a branched, architecture. Given the topotactic nature of the polymerization, these results suggest that a high degree of internal order exists in the supramolecular nanofibers formed by the linear PA. On the basis of microscopy, the formation of a polydiacetylene backbone to covalently connect the β-sheets that help form the fibers does not disrupt the fiber shape. Interestingly, we observe the appearance of a polydiacetylene (PDA) circular dichroism band at 547 nm in linear PA nanofibers suggesting the conjugated backbone in the core of the nanostructures is twisted. We believe this CD signal is due to chiral induction by the β-sheets, which are normally twisted in helical fashion. Heating and cooling shows simultaneous changes in β-sheet and conjugated backbone structure, indicating they are both correlated. At the same time, poor polymerization in nanofibers formed by branched PAs indicates that less internal order exists in these nanostructures and, as expected, then a circular dichroism signal is not observed for the conjugated backbone. The general variety of materials investigated here has the obvious potential to couple electronic properties and in vitro bioactivity. Furthermore, the polymerization of monomers in peptide amphiphile assemblies by a rigid conjugated backbone also leads to mechanical robustness and insolubility, two properties that may be important for the patterning of these materials at the cellular scale. PMID:18314978

  20. Identification of random variation in structures and their parameter estimates.

    SciTech Connect

    Farrar, C. R.; Aumann, R. J.; McCarty, A. A.; Olson, C. C.

    2002-01-01

    Structures that are members of an ensemble of nominally identical systems actually differ due to variations in details among individuals. Furthermore, there are variations in the system response of an individual structure that can be attributed to unmeasured conditions (such as temperature and humidity) that are present during experiments. Finally, noise is present in all measurements of structural excitations and responses. For these reasons, there is always random variation associated with the characterizations of structural dynamic systems, and descriptions of results must be in statistical or probabilistic terms;. This study identifies and assesses the sources and the degrees of randomness in a metric of structural dynamics of a given system through experiments and analysis.

  1. Trimethylamine Ν-oxide Influence on the Backbone of Proteins: An Oligoglycine Model

    SciTech Connect

    Hu, Char Y.; Lynch, Gillian C.; Kokubo, Hironori; Pettitt, Bernard M.

    2010-02-15

    The study of organic osmolytes has been pivotal in demonstrating the role of solvent effects on the protein backbone in the folding process. Although a thermodynamic description of the interactions between the protein backbone and osmolyte has been well defined, the structural analysis of the effect of osmolyte on the protein backbone has been incomplete. Therefore, we have performed simulations of a peptide backbone model, glycine₁₅, in protecting osmolyte trimethylamine Ν-oxide (TMAO) solution, in order to determine the effect of the solution structure on the conformation of the peptide backbone. We show that the models chosen show that the ensemble of backbone structures shifts toward a more collapsed state in TMAO solution as compared with pure water solution. The collapse is consistent with preferential exclusion of the osmolyte caused by unfavorable interactions between osmolyte and peptide backbone. The exclusion is caused by strong triplet correlations of osmolyte, water, and peptide backbone. This provides a clear mechanism showing that even a modest concentration of TMAO forces the protein backbone to adopt a more collapsed structure in the absence of side chain effects.

  2. Solar cycle variations of coronal structures

    NASA Astrophysics Data System (ADS)

    Loucif, M. L.; Koutchmy, S.

    1989-01-01

    Using eclipse pictures of the solar corona, properly scaled drawings have been prepared to constitute a short atlas of coronal structures. These drawings have been used to extract 2 parameters which are further considered with respect to the sunspot number and the sunspot cycle: the extension of polar regions free of coronal streamers and the average radial deviation of large streamers. The flattening index deduced from the photometric analysis of a larger number of eclipse pictures is also considered. The out-of-phase behavior of several coronal parameters is confirmed. The results are discussed in the light of the analysis of the green-line activity as observed during 30 years at the Pic du Midi Observatory. The N-S asymmetric behavior of the activity in different solar hemispheres and the occurrence of a powerful secondary maximum of coronal activity are discussed.

  3. A Variational Monte Carlo Approach to Atomic Structure

    ERIC Educational Resources Information Center

    Davis, Stephen L.

    2007-01-01

    The practicality and usefulness of variational Monte Carlo calculations to atomic structure are demonstrated. It is found to succeed in quantitatively illustrating electron shielding, effective nuclear charge, l-dependence of the orbital energies, and singlet-tripetenergy splitting and ionization energy trends in atomic structure theory.

  4. The novel structure of the core oligosaccharide backbone of the lipopolysaccharide from the Plesiomonas shigelloides strain CNCTC 80/89 (serotype O13).

    PubMed

    Kaszowska, Marta; Jachymek, Wojciech; Niedziela, Tomasz; Koj, Sabina; Kenne, Lennart; Lugowski, Czeslaw

    2013-10-18

    The new structure of the core oligosaccharide of Plesiomonas shigelloides CNCTC 80/89 (serotype O13) lipopolysaccharide has been investigated by chemical methods, (1)H and (13)C NMR spectroscopy and matrix-assisted laser-desorption/ionization time of flight (MALDI-TOF). It was concluded that the core oligosaccharide of P. shigelloides CNCTC 80/89 is a nonasaccharide with the following structure: The position of glycine was determined by MALDI-TOF MS/MS analyses. PMID:23920477

  5. Effects of phosphorylation on the intrinsic propensity of backbone conformations of serine/threonine.

    PubMed

    He, Erbin; Yan, Guanghui; Zhang, Jian; Wang, Jun; Li, Wenfei

    2016-03-01

    Each amino acid has its intrinsic propensity for certain local backbone conformations, which can be further modulated by the physicochemical environment and post-translational modifications. In this work, we study the effects of phosphorylation on the intrinsic propensity for different local backbone conformations of serine/threonine by molecular dynamics simulations. We showed that phosphorylation has very different effects on the intrinsic propensity for certain local backbone conformations for the serine and threonine. The phosphorylation of serine increases the propensity of forming polyproline II, whereas that of threonine has the opposite effect. Detailed analysis showed that such different responses to phosphorylation mainly arise from their different perturbations to the backbone hydration and the geometrical constraints by forming side-chain-backbone hydrogen bonds due to phosphorylation. Such an effect of phosphorylation on backbone conformations can be crucial for understanding the molecular mechanism of phosphorylation-regulated protein structures/dynamics and functions. PMID:26759163

  6. Adding Diverse Noncanonical Backbones to Rosetta: Enabling Peptidomimetic Design

    PubMed Central

    Craven, Timothy W.; Butterfoss, Glenn L.; Chou, Fang-Chieh; Lyskov, Sergey; Bullock, Brooke N.; Watkins, Andrew; Labonte, Jason W.; Pacella, Michael; Kilambi, Krishna Praneeth; Leaver-Fay, Andrew; Kuhlman, Brian; Gray, Jeffrey J.; Bradley, Philip; Kirshenbaum, Kent; Arora, Paramjit S.; Das, Rhiju; Bonneau, Richard

    2013-01-01

    Peptidomimetics are classes of molecules that mimic structural and functional attributes of polypeptides. Peptidomimetic oligomers can frequently be synthesized using efficient solid phase synthesis procedures similar to peptide synthesis. Conformationally ordered peptidomimetic oligomers are finding broad applications for molecular recognition and for inhibiting protein-protein interactions. One critical limitation is the limited set of design tools for identifying oligomer sequences that can adopt desired conformations. Here, we present expansions to the ROSETTA platform that enable structure prediction and design of five non-peptidic oligomer scaffolds (noncanonical backbones), oligooxopiperazines, oligo-peptoids, -peptides, hydrogen bond surrogate helices and oligosaccharides. This work is complementary to prior additions to model noncanonical protein side chains in ROSETTA. The main purpose of our manuscript is to give a detailed description to current and future developers of how each of these noncanonical backbones was implemented. Furthermore, we provide a general outline for implementation of new backbone types not discussed here. To illustrate the utility of this approach, we describe the first tests of the ROSETTA molecular mechanics energy function in the context of oligooxopiperazines, using quantum mechanical calculations as comparison points, scanning through backbone and side chain torsion angles for a model peptidomimetic. Finally, as an example of a novel design application, we describe the automated design of an oligooxopiperazine that inhibits the p53-MDM2 protein-protein interaction. For the general biological and bioengineering community, several noncanonical backbones have been incorporated into web applications that allow users to freely and rapidly test the presented protocols (http://rosie.rosettacommons.org). This work helps address the peptidomimetic community's need for an automated and expandable modeling tool for noncanonical

  7. Thin Films Formed from Conjugated Polymers with Ionic, Water-Soluble Backbones.

    PubMed

    Voortman, Thomas P; Chiechi, Ryan C

    2015-12-30

    This paper compares the morphologies of films of conjugated polymers in which the backbone (main chain) and pendant groups are varied between ionic/hydrophilic and aliphatic/hydrophobic. We observe that conjugated polymers in which the pendant groups and backbone are matched, either ionic-ionic or hydrophobic-hydrophobic, form smooth, structured, homogeneous films from water (ionic) or tetrahydrofuran (hydrophobic). Mismatched conjugated polymers, by contrast, form inhomogeneous films with rough topologies. The polymers with ionic backbone chains are conjugated polyions (conjugated polymers with closed-shell charges in the backbone), which are semiconducting materials with tunable bad-gaps, not unlike uncharged conjugated polymers. PMID:25723354

  8. New insights about pilus formation in gut-adapted Lactobacillus rhamnosus GG from the crystal structure of the SpaA backbone-pilin subunit

    PubMed Central

    Chaurasia, Priyanka; Pratap, Shivendra; von Ossowski, Ingemar; Palva, Airi; Krishnan, Vengadesan

    2016-01-01

    Thus far, all solved structures of pilin-proteins comprising sortase-assembled pili are from pathogenic genera and species. Here, we present the first crystal structure of a pilin subunit (SpaA) from a non-pathogen host (Lactobacillus rhamnosus GG). SpaA consists of two tandem CnaB-type domains, each with an isopeptide bond and E-box motif. Intriguingly, while the isopeptide bond in the N-terminal domain forms between lysine and asparagine, the one in the C-terminal domain atypically involves aspartate. We also solved crystal structures of mutant proteins where residues implicated in forming isopeptide bonds were replaced. Expectedly, the E-box-substituted E139A mutant lacks an isopeptide bond in the N-terminal domain. However, the C-terminal E269A substitution gave two structures; one of both domains with their isopeptide bonds present, and another of only the N-terminal domain, but with an unformed isopeptide bond and significant conformational changes. This latter crystal structure has never been observed for any other Gram-positive pilin. Notably, the C-terminal isopeptide bond still forms in D295N-substituted SpaA, irrespective of E269 being present or absent. Although E-box mutations affect SpaA proteolytic and thermal stability, a cumulative effect perturbing normal pilus polymerization was unobserved. A model showing the polymerized arrangement of SpaA within the SpaCBA pilus is proposed. PMID:27349405

  9. New insights about pilus formation in gut-adapted Lactobacillus rhamnosus GG from the crystal structure of the SpaA backbone-pilin subunit.

    PubMed

    Chaurasia, Priyanka; Pratap, Shivendra; von Ossowski, Ingemar; Palva, Airi; Krishnan, Vengadesan

    2016-01-01

    Thus far, all solved structures of pilin-proteins comprising sortase-assembled pili are from pathogenic genera and species. Here, we present the first crystal structure of a pilin subunit (SpaA) from a non-pathogen host (Lactobacillus rhamnosus GG). SpaA consists of two tandem CnaB-type domains, each with an isopeptide bond and E-box motif. Intriguingly, while the isopeptide bond in the N-terminal domain forms between lysine and asparagine, the one in the C-terminal domain atypically involves aspartate. We also solved crystal structures of mutant proteins where residues implicated in forming isopeptide bonds were replaced. Expectedly, the E-box-substituted E139A mutant lacks an isopeptide bond in the N-terminal domain. However, the C-terminal E269A substitution gave two structures; one of both domains with their isopeptide bonds present, and another of only the N-terminal domain, but with an unformed isopeptide bond and significant conformational changes. This latter crystal structure has never been observed for any other Gram-positive pilin. Notably, the C-terminal isopeptide bond still forms in D295N-substituted SpaA, irrespective of E269 being present or absent. Although E-box mutations affect SpaA proteolytic and thermal stability, a cumulative effect perturbing normal pilus polymerization was unobserved. A model showing the polymerized arrangement of SpaA within the SpaCBA pilus is proposed. PMID:27349405

  10. Gorilla genome structural variation reveals evolutionary parallelisms with chimpanzee.

    PubMed

    Ventura, Mario; Catacchio, Claudia R; Alkan, Can; Marques-Bonet, Tomas; Sajjadian, Saba; Graves, Tina A; Hormozdiari, Fereydoun; Navarro, Arcadi; Malig, Maika; Baker, Carl; Lee, Choli; Turner, Emily H; Chen, Lin; Kidd, Jeffrey M; Archidiacono, Nicoletta; Shendure, Jay; Wilson, Richard K; Eichler, Evan E

    2011-10-01

    Structural variation has played an important role in the evolutionary restructuring of human and great ape genomes. Recent analyses have suggested that the genomes of chimpanzee and human have been particularly enriched for this form of genetic variation. Here, we set out to assess the extent of structural variation in the gorilla lineage by generating 10-fold genomic sequence coverage from a western lowland gorilla and integrating these data into a physical and cytogenetic framework of structural variation. We discovered and validated over 7665 structural changes within the gorilla lineage, including sequence resolution of inversions, deletions, duplications, and mobile element insertions. A comparison with human and other ape genomes shows that the gorilla genome has been subjected to the highest rate of segmental duplication. We show that both the gorilla and chimpanzee genomes have experienced independent yet convergent patterns of structural mutation that have not occurred in humans, including the formation of subtelomeric heterochromatic caps, the hyperexpansion of segmental duplications, and bursts of retroviral integrations. Our analysis suggests that the chimpanzee and gorilla genomes are structurally more derived than either orangutan or human genomes. PMID:21685127

  11. Impact of template backbone heterogeneity on RNA polymerase II transcription

    PubMed Central

    Xu, Liang; Wang, Wei; Zhang, Lu; Chong, Jenny; Huang, Xuhui; Wang, Dong

    2015-01-01

    Variations in the sugar component (ribose or deoxyribose) and the nature of the phosphodiester linkage (3′-5′ or 2′-5′ orientation) have been a challenge for genetic information transfer from the very beginning of evolution. RNA polymerase II (pol II) governs the transcription of DNA into precursor mRNA in all eukaryotic cells. How pol II recognizes DNA template backbone (phosphodiester linkage and sugar) and whether it tolerates the backbone heterogeneity remain elusive. Such knowledge is not only important for elucidating the chemical basis of transcriptional fidelity but also provides new insights into molecular evolution. In this study, we systematically and quantitatively investigated pol II transcriptional behaviors through different template backbone variants. We revealed that pol II can well tolerate and bypass sugar heterogeneity sites at the template but stalls at phosphodiester linkage heterogeneity sites. The distinct impacts of these two backbone components on pol II transcription reveal the molecular basis of template recognition during pol II transcription and provide the evolutionary insight from the RNA world to the contemporary ‘imperfect’ DNA world. In addition, our results also reveal the transcriptional consequences from ribose-containing genomic DNA. PMID:25662224

  12. Challenges and standards in integrating surveys of structural variation

    PubMed Central

    Scherer, Stephen W; Lee, Charles; Birney, Ewan; Altshuler, David M; Eichler, Evan E; Carter, Nigel P; Hurles, Matthew E; Feuk, Lars

    2009-01-01

    There has been an explosion of data describing newly recognized structural variants in the human genome. In the flurry of reporting, there has been no standard approach to collecting the data, assessing its quality or describing identified features. This risks becoming a rampant problem, in particular with respect to surveys of copy number variation and their application to disease studies. Here, we consider the challenges in characterizing and documenting genomic structural variants. From this, we derive recommendations for standards to be adopted, with the aim of ensuring the accurate presentation of this form of genetic variation to facilitate ongoing research. PMID:17597783

  13. Flexible backbone aromatic polyimide adhesives

    NASA Technical Reports Server (NTRS)

    Progar, Donald J.; St.clair, Terry L.

    1988-01-01

    Continuing research at Langley Research Center on the synthesis and development of new inexpensive flexible aromatic polyimides as adhesives has resulted in a material identified as LARC-F-SO2 with similarities to polyimidesulfone, PISO2, and other flexible backbone polyimides recently reported by Progar and St. Clair. Also prepared and evaluated was an endcapped version of PISO2. These two polymers were compared with LARC-TPI and LARC-STPI, polyimides research in our laboratory and reported in the literature. The adhesive evaluation, primarily based on lap shear strength (LSS) tests at RT, 177 C and 204 C, involved preparing adhesive tapes, conducting bonding studies and exposing lap shear specimens to 204 C air for up to 1000 hrs and to a 72-hour water boil. The type of adhesive failure as well as the Tg was determined for the fractured specimens. The results indicate that LARC-TPI provides the highest LSSs. LARC-F-SO2, LARC-TPI and LARC-STPI all retain their strengths after thermal exposure for 1000 hrs and PISO2 retains greater than 80 percent of its control strengths. After a 72-hr water boil exposure, most of the four adhesive systems showed reduced strengths for all test temperatures although still retaining a high percentage of their original strength (greater than 60 percent) except for one case. The predominant failure type was cohesive with no significant change in the Tgs.

  14. Flexible backbone aromatic polyimide adhesives

    NASA Technical Reports Server (NTRS)

    Progar, Donald J.; St. Clair, Terry L.

    1989-01-01

    Continuing research at Langley Research Center on the synthesis and development of new inexpensive flexible aromatic polyimides as adhesives has resulted in a material identified as LARC-F-SO2 with similarities to polyimidesulfone, PISO2, and other flexible backbone polyimides recently reported by Progar and St. Clair. Also prepared and evaluated was an endcapped version of PISO2. These two polymers were compared with LARC-TPI and LARC-STPI, polyimides research in our laboratory and reported in the literature. The adhesive evaluation, primarily based on lap shear strength (LSS) tests at RT, 177 C and 204 C, involved preparing adhesive tapes, conducting bonding studies and exposing lap shear specimens to 204 C air for up to 1000 hrs and to a 72-hour water boil. The type of adhesive failure as well as the Tg was determined for the fractured specimens. The results indicate that LARC-TPI provides the highest LSSs. LARC-F-SO2, LARC-TPI and LARC-STPI all retain their strengths after thermal exposure for 1000 hrs and PISO2 retains greater than 80 percent of its control strengths. After a 72-hr water boil exposure, most of the four adhesive systems showed reduced strengths for all test temperatures although still retaining a high percentage of their original strength (greater than 60 percent) except for one case. The predominant failure type was cohesive with no significant change in the Tgs.

  15. 55P0110, a Novel Synthetic Compound Developed from a Plant Derived Backbone Structure, Shows Promising Anti-Hyperglycaemic Activity in Mice.

    PubMed

    Brunmair, Barbara; Lehner, Zsuzsanna; Stadlbauer, Karin; Adorjan, Immanuel; Frobel, Klaus; Scherer, Thomas; Luger, Anton; Bauer, Leonhardt; Fürnsinn, Clemens

    2015-01-01

    Starting off with a structure derived from the natural compound multiflorine, a derivatisation program aimed at the discovery and initial characterisation of novel compounds with antidiabetic potential. Design and discovery of the structures was guided by oral bioactivities obtained in oral glucose tolerance tests in mice. 55P0110, one among several new compounds with distinct anti-hyperglycaemic activity, was further examined to characterise its pharmacology and mode of action. Whereas a single oral dose of 55P0110 did not affect basal glycaemia, it markedly improved the glucose tolerance of healthy and diabetic mice (peak blood glucose in glucose tolerance test, mmol/l: healthy mice with 90 mg/kg 55P0110, 17.0 ± 1.2 vs. 10.1 ± 1.1; diabetic mice with 180 mg/kg 55P0110, 23.1 ± 0.9 vs. 11.1 ± 1.4; p<0.001 each). Closer examination argued against retarded glucose resorption from the gut, increased glucose excretion in urine, acute insulin-like or insulin sensitising properties, and direct inhibition of dipeptidyl peptidase-4 as the cause of glucose lowering. Hence, 55P0110 seems to act via a target not exploited by any drug presently approved for the treatment of diabetes mellitus. Whereas the insulinotropic sulfonylurea gliclazide (16 mg/kg) distinctly increased the circulating insulin-per-glucose ratio under basal conditions, 55P0110 (90 mg/kg) lacked such an effect (30 min. after dosing, nmol/mol: vehicle, 2.49 ± 0.27; 55P0110, 2.99 ± 0.35; gliclazide, 8.97 ± 0.49; p<0.001 each vs. gliclazide). Under an exogenous glucose challenge, however, 55P0110 increased this ratio to the same extent as gliclazide (20 min. after glucose feeding: vehicle, 2.53 ± 0.41; 55P0110, 3.80 ± 0.46; gliclazide, 3.99 ± 0.26; p<0.05 each vs. vehicle). By augmenting the glucose stimulated increase in plasma insulin, 55P0110 thus shows distinct anti-hyperglycaemic action in combination with low risk for fasting hypoglycaemia in mice. In summary, we have discovered a novel class of

  16. 55P0110, a Novel Synthetic Compound Developed from a Plant Derived Backbone Structure, Shows Promising Anti-Hyperglycaemic Activity in Mice

    PubMed Central

    Brunmair, Barbara; Lehner, Zsuzsanna; Stadlbauer, Karin; Adorjan, Immanuel; Frobel, Klaus; Scherer, Thomas; Luger, Anton; Bauer, Leonhardt; Fürnsinn, Clemens

    2015-01-01

    Starting off with a structure derived from the natural compound multiflorine, a derivatisation program aimed at the discovery and initial characterisation of novel compounds with antidiabetic potential. Design and discovery of the structures was guided by oral bioactivities obtained in oral glucose tolerance tests in mice. 55P0110, one among several new compounds with distinct anti-hyperglycaemic activity, was further examined to characterise its pharmacology and mode of action. Whereas a single oral dose of 55P0110 did not affect basal glycaemia, it markedly improved the glucose tolerance of healthy and diabetic mice (peak blood glucose in glucose tolerance test, mmol/l: healthy mice with 90 mg/kg 55P0110, 17.0±1.2 vs. 10.1±1.1; diabetic mice with 180 mg/kg 55P0110, 23.1±0.9 vs. 11.1±1.4; p<0.001 each). Closer examination argued against retarded glucose resorption from the gut, increased glucose excretion in urine, acute insulin-like or insulin sensitising properties, and direct inhibition of dipeptidyl peptidase-4 as the cause of glucose lowering. Hence, 55P0110 seems to act via a target not exploited by any drug presently approved for the treatment of diabetes mellitus. Whereas the insulinotropic sulfonylurea gliclazide (16 mg/kg) distinctly increased the circulating insulin-per-glucose ratio under basal conditions, 55P0110 (90 mg/kg) lacked such an effect (30 min. after dosing, nmol/mol: vehicle, 2.49±0.27; 55P0110, 2.99±0.35; gliclazide, 8.97±0.49; p<0.001 each vs. gliclazide). Under an exogenous glucose challenge, however, 55P0110 increased this ratio to the same extent as gliclazide (20 min. after glucose feeding: vehicle, 2.53±0.41; 55P0110, 3.80±0.46; gliclazide, 3.99±0.26; p<0.05 each vs. vehicle). By augmenting the glucose stimulated increase in plasma insulin, 55P0110 thus shows distinct anti-hyperglycaemic action in combination with low risk for fasting hypoglycaemia in mice. In summary, we have discovered a novel class of fully synthetic

  17. Solar cycle variation of large-scale coronal structures

    NASA Technical Reports Server (NTRS)

    Antonucci, E.; Duvall, T. L.

    1974-01-01

    A green line intensity variation is associated with the interplanetary and photospheric magnetic sector structure. This effect depends on the solar cycle and occurs with the same amplitude in the latitude range 60 deg N - 60 deg S. Extended longitudinal coronal structures are suggested, which indicate the existence of closed magnetic field lines over the neutral line, separating adjacent regions of opposite polarities on the photospheric surface.

  18. Bats aloft: Variation in echolocation call structure at high altitudes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bats alter their echolocation calls in response to changes in ecological and behavioral conditions, but little is known about how they adjust their call structure in response to changes in altitude. This study examines altitudinal variation in the echolocation calls of Brazilian free-tailed bats, T...

  19. Free backbone carbonyls mediate rhodopsin activation.

    PubMed

    Kimata, Naoki; Pope, Andreyah; Sanchez-Reyes, Omar B; Eilers, Markus; Opefi, Chikwado A; Ziliox, Martine; Reeves, Philip J; Smith, Steven O

    2016-08-01

    Conserved prolines in the transmembrane helices of G-protein-coupled receptors (GPCRs) are often considered to function as hinges that divide the helix into two segments capable of independent motion. Depending on their potential to hydrogen-bond, the free C=O groups associated with these prolines can facilitate conformational flexibility, conformational switching or stabilization of the receptor structure. To address the role of conserved prolines in family A GPCRs through solid-state NMR spectroscopy, we focus on bovine rhodopsin, a GPCR in the visual receptor subfamily. The free backbone C=O groups on helices H5 and H7 stabilize the inactive rhodopsin structure through hydrogen-bonds to residues on adjacent helices. In response to light-induced isomerization of the retinal chromophore, hydrogen-bonding interactions involving these C=O groups are released, thus facilitating repacking of H5 and H7 onto the transmembrane core of the receptor. These results provide insights into the multiple structural and functional roles of prolines in membrane proteins. PMID:27376589

  20. Periodicity, planarity, and pixel (3P): a program using the intrinsic residual dipolar coupling periodicity-to-peptide plane correlation and phi/psi angles to derive protein backbone structures.

    PubMed

    Wang, Jinbu; Walsh, Joseph D; Kuszewski, John; Wang, Yun-Xing

    2007-11-01

    We present a detailed description of a theory and a program called 3P. "3P" stands for periodicity, planarity, and pixel. The 3P program is based on the intrinsic periodic correlations between residual dipolar couplings (RDCs) and in-plane internuclear vectors, and between RDCs and the orientation of peptide planes relative to an alignment tensor. The program extracts accurate rhombic, axial components of the alignment tensor without explicit coordinates, and discrete peptide plane orientations, which are utilized in combination with readily available phi/psi angles to determine the three-dimensional backbone structures of proteins. The 3P program uses one alignment tensor. We demonstrate the utility and robustness of the program, using both experimental and synthetic data sets, which were added with different levels of noise or were incomplete. The program is interfaced to Xplor-NIH via a "3P" module and is available to the public. The limitations and differences between our program and existing methods are also discussed. PMID:17892961

  1. New Tests for Variations of the Fine Structure Constant

    NASA Technical Reports Server (NTRS)

    Prestage, John D.

    1995-01-01

    We describe a new test for possible variations of the fine structure constant, by comparisons of rates between clocks based on hyperfine transitions in alkali atomos with different atomic number Z. H- maser, Cs and Hg+ clocks have a different dependence on ia relativistic contributions of order (Z. Recent H-maser vs Hg+ clock comparison data improves laboratory limits on a time variation by 100-fold to giveFuture laser cooled clocks (Be+, Rb, Cs, Hg+, etc.), when compared, will yield the most senstive of all tests for.

  2. Major Variations in HIV-1 Capsid Assembly Morphologies Involve Minor Variations in Molecular Structures of Structurally Ordered Protein Segments.

    PubMed

    Lu, Jun-Xia; Bayro, Marvin J; Tycko, Robert

    2016-06-17

    We present the results of solid state nuclear magnetic resonance (NMR) experiments on HIV-1 capsid protein (CA) assemblies with three different morphologies, namely wild-type CA (WT-CA) tubes with 35-60 nm diameters, planar sheets formed by the Arg(18)-Leu mutant (R18L-CA), and R18L-CA spheres with 20-100 nm diameters. The experiments are intended to elucidate molecular structural variations that underlie these variations in CA assembly morphology. We find that multidimensional solid state NMR spectra of (15)N,(13)C-labeled CA assemblies are remarkably similar for the three morphologies, with only small differences in (15)N and (13)C chemical shifts, no significant differences in NMR line widths, and few differences in the number of detectable NMR cross-peaks. Thus, the pronounced differences in morphology do not involve major differences in the conformations and identities of structurally ordered protein segments. Instead, morphological variations are attributable to variations in conformational distributions within disordered segments, which do not contribute to the solid state NMR spectra. Variations in solid state NMR signals from certain amino acid side chains are also observed, suggesting differences in the intermolecular dimerization interface between curved and planar CA lattices, as well as possible differences in intramolecular helix-helix packing. PMID:27129282

  3. Computation-Guided Backbone Grafting of a Discontinuous Motif onto a Protein Scaffold

    SciTech Connect

    Azoitei, Mihai L.; Correia, Bruno E.; Ban, Yih-En Andrew; Carrico, Chris; Kalyuzhniy, Oleksandr; Chen, Lei; Schroeter, Alexandria; Huang, Po-Ssu; McLellan, Jason S.; Kwong, Peter D.; Baker, David; Strong, Roland K.; Schief, William R.

    2012-02-07

    The manipulation of protein backbone structure to control interaction and function is a challenge for protein engineering. We integrated computational design with experimental selection for grafting the backbone and side chains of a two-segment HIV gp120 epitope, targeted by the cross-neutralizing antibody b12, onto an unrelated scaffold protein. The final scaffolds bound b12 with high specificity and with affinity similar to that of gp120, and crystallographic analysis of a scaffold bound to b12 revealed high structural mimicry of the gp120-b12 complex structure. The method can be generalized to design other functional proteins through backbone grafting.

  4. Latitudinal variation in population structure of wintering Pacific Black Brant

    USGS Publications Warehouse

    Schamber, J.L.; Sedinger, J.S.; Ward, D.H.; Hagmeier, K.R.

    2007-01-01

    Latitudinal variation in population structure during the winter has been reported in many migratory birds, but has been documented in few species of waterfowl. Variation in environmental and social conditions at wintering sites can potentially influence the population dynamics of differential migrants. We examined latitudinal variation in sex and age classes of wintering Pacific Black Brant (Branta bernicla nigricans). Brant are distributed along a wide latitudinal gradient from Alaska to Mexico during the winter. Accordingly, migration distances for brant using different wintering locations are highly variable and winter settlement patterns are likely associated with a spatially variable food resource. We used resightings of brant banded in southwestern Alaska to examine sex and age ratios of birds wintering at Boundary Bay in British Columbia, and at San Quintin Bay, Ojo de Liebre Lagoon, and San Ignacio Lagoon in Baja California from 1998 to 2000. Sex ratios were similar among wintering locations for adults and were consistent with the mating strategy of geese. The distribution of juveniles varied among wintering areas, with greater proportions of juveniles observed at northern (San Quintin Bay and Ojo de Liebre Lagoon) than at southern (San Ignacio Lagoon) locations in Baja California. We suggest that age-related variation in the winter distribution of Pacific Black Brant is mediated by variation in productivity among individuals at different wintering locations and by social interactions among wintering family groups.

  5. CONSERTING: integrating copy number analysis with structural variation detection

    PubMed Central

    Chen, Xiang; Gupta, Pankaj; Wang, Jianmin; Nakitandwe, Joy; Roberts, Kathryn; Dalton, James D.; Parker, Matthew; Patel, Samir; Holmfeldt, Linda; Payne, Debbie; Easton, John; Ma, Jing; Rusch, Michael; Wu, Gang; Patel, Aman; J. Baker, Suzanne; Dyer, Michael A.; Shurtleff, Sheila; Espy, Stephen; Pounds, Stanley; Downing, James R.; Ellison, David W.; Mullighan, Charles G.; Zhang, Jinghui

    2015-01-01

    We developed Copy Number Segmentation by Regression Tree in Next Generation Sequencing (CONSERTING), a novel algorithm for detecting somatic copy number alteration (CNA) using whole-genome sequencing (WGS) data. CONSERTING performs iterative analysis of segmentation by read depth change and localized structural variation detection, achieving high accuracy and sensitivity. Analysis of 43 pediatric and adult cancer genomes revealed novel oncogenic CNAs, complex re-arrangements and subclonal CNAs missed by alternative approaches. PMID:25938371

  6. Controls-structures integrated design optimization with shape variations

    NASA Technical Reports Server (NTRS)

    Koganti, Gopichand; Hou, Gene

    1993-01-01

    The shape design variables have been introduced into the set of design variables of the Controls-Structure Integrated (CSI) Design of space-structures. The importance of the shape variations in improving the design (obtained with only control and sizing variables) has been aptly illustrated. Two different types of design variables that describe the shape variations of the structure have been introduced. In the first case, the nodal coordinates have been considered as design variables. This has the inherent difficulty of having too many design variables. This not only is time consuming but also memory intensive and may not yield a manufacturable shape to the structure. The second approach has been introduced to overcome this difficulty. The structure is allowed to vary in a particular pre defined pattern. The coefficients of these patterns are considered as the shape design variables. The eigenvalue and eigenvector sensitivity equations with respect to these coefficient design variables have been developed and are used to approximate the eigenvalues and eigenvectors in a perturbed design.

  7. NET amyloidogenic backbone in human activated neutrophils.

    PubMed

    Pulze, L; Bassani, B; Gini, E; D'Antona, P; Grimaldi, A; Luini, A; Marino, F; Noonan, D M; Tettamanti, G; Valvassori, R; de Eguileor, M

    2016-03-01

    Activated human neutrophils produce a fibrillar DNA network [neutrophil extracellular traps (NETs)] for entrapping and killing bacteria, fungi, protozoa and viruses. Our results suggest that the neutrophil extracellular traps show a resistant amyloidogenic backbone utilized for addressing reputed proteins and DNA against the non-self. The formation of amyloid fibrils in neutrophils is regulated by the imbalance of reactive oxygen species (ROS) in the cytoplasm. The intensity and source of the ROS signal is determinant for promoting stress-associated responses such as amyloidogenesis and closely related events: autophagy, exosome release, activation of the adrenocorticotrophin hormone/α-melanocyte-stimulating hormone (ACTH/α-MSH) loop and synthesis of specific cytokines. These interconnected responses in human activated neutrophils, that have been evaluated from a morphofunctional and quantitative viewpoint, represent primitive, but potent, innate defence mechanisms. In invertebrates, circulating phagocytic immune cells, when activated, show responses similar to those described previously for activated human neutrophils. Invertebrate cells within endoplasmic reticulum cisternae produce a fibrillar material which is then assembled into an amyloidogenic scaffold utilized to convey melanin close to the invader. These findings, in consideration to the critical role played by NET in the development of several pathologies, could explain the structural resistance of these scaffolds and could provide the basis for developing new diagnostic and therapeutic approaches in immunomediated diseases in which the innate branch of the immune system has a pivotal role. PMID:26462606

  8. Variation in compound eye structure: effects of diet and family.

    PubMed

    Merry, Justin W; Kemp, Darrell J; Rutowski, Ronald L

    2011-07-01

    Studies of compound eyes have revealed that variation in eye structure can substantially affect visual performance. Here, we investigate the degree to which a stressful rearing environment, which decreases body size, affects the eye phenotype. Full siblings of the Orange Sulphur butterfly, Colias eurytheme, were collected from known parents and split within families among two diet treatments that varied in quality. In both sexes, individuals reared on the high-quality diet had larger eye height and anterior facet diameter, and therefore, by inference, superior vision. However, relative to their reduced body size, individuals reared on low-quality diet had proportionally larger eyes and facets than individuals reared on high-quality diet. We interpret this finding as evidence that butterflies encountering nutritional stress increased proportional investment in eye development to reduce loss of visual performance. We also found significant broad-sense genetic variation underlying eye structure in both males and females, and report novel heritability estimates for eye height and facet diameter. Surprisingly, there was greater genetic variation in eye height among males than among females, despite apparently stronger directional selection on male vision. We discuss the implications of these data for our understanding of eye development and evolution. PMID:21729063

  9. Increasing Sequence Diversity with Flexible Backbone Protein Design: The Complete Redesign of a Protein Hydrophobic Core

    SciTech Connect

    Murphy, Grant S.; Mills, Jeffrey L.; Miley, Michael J.; Machius, Mischa; Szyperski, Thomas; Kuhlman, Brian

    2015-10-15

    Protein design tests our understanding of protein stability and structure. Successful design methods should allow the exploration of sequence space not found in nature. However, when redesigning naturally occurring protein structures, most fixed backbone design algorithms return amino acid sequences that share strong sequence identity with wild-type sequences, especially in the protein core. This behavior places a restriction on functional space that can be explored and is not consistent with observations from nature, where sequences of low identity have similar structures. Here, we allow backbone flexibility during design to mutate every position in the core (38 residues) of a four-helix bundle protein. Only small perturbations to the backbone, 12 {angstrom}, were needed to entirely mutate the core. The redesigned protein, DRNN, is exceptionally stable (melting point >140C). An NMR and X-ray crystal structure show that the side chains and backbone were accurately modeled (all-atom RMSD = 1.3 {angstrom}).

  10. Atomic Clocks and Variations of the FIne Structure Constant

    NASA Technical Reports Server (NTRS)

    Prestage, John D.; Tjoelker, Robert L.; Maleki, Lute

    1995-01-01

    We describe a new test for possible variations of the fine structure constant alpha by comparisons of rates between clocks based on hyperfine transitions in alkali atoms with different atomic number Z. H-maser, Cs, and Hg(+) clocks have a different dependence on alpha via relativistic contributions of order (Z-alpha)(sup 2). Recent H-maser vs Hg(+) clock comparison data improve laboratory limits on a time variation by 100-fold to give dot-alpha less than or equal to 3.7 x 10(exp -14)/yr. Future laser cooled clocks (Be(+), Rb, Cs, Hg(+), etc.), when compared, will yield the most sensitive of all tests for dot-alpha/alpha.

  11. Variational structure of inverse problems in wave propagation and vibration

    SciTech Connect

    Berryman, J.G.

    1995-03-01

    Practical algorithms for solving realistic inverse problems may often be viewed as problems in nonlinear programming with the data serving as constraints. Such problems are most easily analyzed when it is possible to segment the solution space into regions that are feasible (satisfying all the known constraints) and infeasible (violating some of the constraints). Then, if the feasible set is convex or at least compact, the solution to the problem will normally lie on the boundary of the feasible set. A nonlinear program may seek the solution by systematically exploring the boundary while satisfying progressively more constraints. Examples of inverse problems in wave propagation (traveltime tomography) and vibration (modal analysis) will be presented to illustrate how the variational structure of these problems may be used to create nonlinear programs using implicit variational constraints.

  12. Interplay among side chain sequence, backbone composition, and residue rigidification in polypeptide folding and assembly

    PubMed Central

    Horne, W. Seth; Price, Joshua L.; Gellman, Samuel H.

    2008-01-01

    The extent to which polypeptide conformation depends on side-chain composition and sequence has been widely studied, but less is known about the importance of maintaining an α-amino acid backbone. Here, we examine a series of peptides with backbones that feature different repeating patterns of α- and β-amino acid residues but an invariant side-chain sequence. In the pure α-backbone, this sequence corresponds to the previously studied peptide GCN4-pLI, which forms a very stable four-helix bundle quaternary structure. Physical characterization in solution and crystallographic structure determination show that a variety of α/β-peptide backbones can adopt sequence-encoded quaternary structures similar to that of the α prototype. There is a loss in helix bundle stability upon β-residue incorporation; however, stability of the quaternary structure is not a simple function of β-residue content. We find that cyclically constrained β-amino acid residues can stabilize the folds of α/β-peptide GCN4-pLI analogues and restore quaternary structure formation to backbones that are predominantly unfolded in the absence of cyclic residues. Our results show a surprising degree of plasticity in terms of the backbone compositions that can manifest the structural information encoded in a sequence of amino acid side chains. These findings offer a framework for the design of nonnatural oligomers that mimic the structural and functional properties of proteins. PMID:18587049

  13. Mapping the backbone of science.

    SciTech Connect

    Klavans, Richard; BÞorner, Katy; Boyack, Kevin W.

    2004-11-01

    This paper presents a new map representing the structure of all of science, based on journal articles, including both the natural and social sciences. Similar to cartographic maps of our world, the map of science provides a bird's eye view of today's scientific landscape. It can be used to visually identify major areas of science, their size, similarity, and interconnectedness. In order to be useful, the map needs to be accurate on a local and on a global scale. While our recent work has focused on the former aspect, this paper summarizes results on how to achieve structural accuracy. Eight alternative measures of journal similarity were applied to a data set of 7,121 journals covering over 1 million documents in the combined Science Citation and Social Science Citation Indexes. For each journal similarity measure we generated two-dimensional spatial layouts using the force-directed graph layout tool, VxOrd. Next, mutual information values were calculated for each graph at different clustering levels to give a measure of structural accuracy for each map. The best co-citation and inter-citation maps according to local and structural accuracy were selected and are presented and characterized. These two maps are compared to establish robustness. The inter-citation map is then used to examine linkages between disciplines. Biochemistry appears as the most interdisciplinary discipline in science.

  14. Crustal structure in and around the Onikobe geothermal area, northeastern Honshu, Japan, inferred from the spatial variation of coda decay

    NASA Astrophysics Data System (ADS)

    Hasemi, Akiko; Miura, Hidetoshi; Ishizawa, Mari; Kosuga, Masahiro; Umino, Norihito; Hasegawa, Akira

    2015-07-01

    The Onikobe area is an active geothermal area situated in the Ou backbone range of northeastern Honshu, Japan. It is home to calderas from the Tertiary to Quaternary eras and active volcanoes. A systematic spatial variation of Qc has been found in this area: Qc values are lower at stations in and around calderas than at other stations. The amplitude of coda waves with high Qcs decreases more slowly after a lapse time of around 7-10 s than that with low Qcs. In the present study, to determine causes for these coda decay variations, coda envelopes were synthesized in a structure model in which high attenuation zones existed beneath the Onikobe and Sanzugawa calderas and where scattering coefficients were higher in the lower crust than in the upper crust. Using hypocenters shallower than 10 km, envelopes were calculated for 256 station-hypocenter pairs with epicentral distances of less than 10 km. It was assumed that the coda waves were composed of S-S scattered waves, and that the scattering was single and isotropic. The observed features of the Qc distribution were reproduced in the synthesis, and synthesized envelopes were found to mostly coincide with observed decay curves. The top of high attenuation zones was thus estimated as being deeper than 7.5 km. The structure assumed for the synthesis was consistent with that of previous studies. We consider that the structure model used was appropriate, and that high attenuation zones beneath calderas and the reflective lower crust caused the spatial variation of the Qc and decay curves in the Onikobe area. We also consider that studies using coda decay would be beneficial in detecting high attenuation zones and the reflective lower crust.

  15. Genome Editing of Structural Variations: Modeling and Gene Correction.

    PubMed

    Park, Chul-Yong; Sung, Jin Jea; Kim, Dong-Wook

    2016-07-01

    The analysis of chromosomal structural variations (SVs), such as inversions and translocations, was made possible by the completion of the human genome project and the development of genome-wide sequencing technologies. SVs contribute to genetic diversity and evolution, although some SVs can cause diseases such as hemophilia A in humans. Genome engineering technology using programmable nucleases (e.g., ZFNs, TALENs, and CRISPR/Cas9) has been rapidly developed, enabling precise and efficient genome editing for SV research. Here, we review advances in modeling and gene correction of SVs, focusing on inversion, translocation, and nucleotide repeat expansion. PMID:27016031

  16. Trabecular bone structural variation throughout the human lower limb.

    PubMed

    Saers, Jaap P P; Cazorla-Bak, Yasmin; Shaw, Colin N; Stock, Jay T; Ryan, Timothy M

    2016-08-01

    Trabecular bone is responsive to mechanical loading, and thus may be a useful tool for interpreting past behaviour from fossil morphology. However, the ability to meaningfully interpret variation in archaeological and hominin trabecular morphology depends on the extent to which trabecular bone properties are integrated throughout the postcranium or are locally variable in response to joint specific loading. We investigate both of these factors by comparing trabecular bone throughout the lower limb between a group of highly mobile foragers and two groups of sedentary agriculturalists. Trabecular bone structure is quantified in four volumes of interest placed within the proximal and distal joints of the femur and tibia. We determine how trabecular structures correspond to inferred behavioural differences between populations and whether the patterns are consistent throughout the limb. A significant correlation was found between inferred mobility level and trabecular bone structure in all volumes of interest along the lower limb. The greater terrestrial mobility of foragers is associated with higher bone volume fraction, and thicker and fewer trabeculae (lower connectivity density). In all populations, bone volume fraction decreases while anisotropy increases proximodistally throughout the lower limb. This observation mirrors reductions in cortical bone mass resulting from proximodistal limb tapering. The reduction in strength associated with reduced bone volume fraction may be compensated for by the increased anisotropy in the distal tibia. A similar pattern of trabecular structure is found throughout the lower limb in all populations, upon which a signal of terrestrial mobility appears to be superimposed. These results support the validity of using lower limb trabecular bone microstructure to reconstruct terrestrial mobility levels from the archaeological and fossil records. The results further indicate that care should be taken to appreciate variation resulting from

  17. Alpha-helical stabilization by side chain shielding of backbone hydrogen bonds.

    PubMed

    García, Angel E; Sanbonmatsu, Kevin Y

    2002-03-01

    We study atomic models of the thermodynamics of the structural transition of peptides that form alpha-helices. The effect of sequence variation on alpha-helix formation for alanine-rich peptides, Ac-Ala21-methyl amide (A21) and Ac-A5 (AAARA)3A-methyl amide (Fs peptide), is investigated by atomic simulation studies of the thermodynamics of the helix-coil transition in explicit water. The simulations show that the guanidinium group in the Arg side chains in the Fs peptide interacts with the carbonyl group four amino acids upstream in the chain and desolvates backbone hydrogen bonds. This desolvation can be directly correlated with a higher probability of hydrogen bond formation. We find that Fs has higher helical content than A21 at all temperatures. A small modification in the amber force field reproduces the experimental helical content and helix-coil transition temperatures for the Fs peptide. PMID:11867710

  18. Statistical Analysis of RNA Backbone

    PubMed Central

    Hershkovitz, Eli; Sapiro, Guillermo; Tannenbaum, Allen; Williams, Loren Dean

    2009-01-01

    Local conformation is an important determinant of RNA catalysis and binding. The analysis of RNA conformation is particularly difficult due to the large number of degrees of freedom (torsion angles) per residue. Proteins, by comparison, have many fewer degrees of freedom per residue. In this work, we use and extend classical tools from statistics and signal processing to search for clusters in RNA conformational space. Results are reported both for scalar analysis, where each torsion angle is separately studied, and for vectorial analysis, where several angles are simultaneously clustered. Adapting techniques from vector quantization and clustering to the RNA structure, we find torsion angle clusters and RNA conformational motifs. We validate the technique using well-known conformational motifs, showing that the simultaneous study of the total torsion angle space leads to results consistent with known motifs reported in the literature and also to the finding of new ones. PMID:17048391

  19. MCBT: Multi-Hop Cluster Based Stable Backbone Trees for Data Collection and Dissemination in WSNs.

    PubMed

    Shin, Inyoung; Kim, Moonseong; Mutka, Matt W; Choo, Hyunseung; Lee, Tae-Jin

    2009-01-01

    We propose a stable backbone tree construction algorithm using multi-hop clusters for wireless sensor networks (WSNs). The hierarchical cluster structure has advantages in data fusion and aggregation. Energy consumption can be decreased by managing nodes with cluster heads. Backbone nodes, which are responsible for performing and managing multi-hop communication, can reduce the communication overhead such as control traffic and minimize the number of active nodes. Previous backbone construction algorithms, such as Hierarchical Cluster-based Data Dissemination (HCDD) and Multicluster, Mobile, Multimedia radio network (MMM), consume energy quickly. They are designed without regard to appropriate factors such as residual energy and degree (the number of connections or edges to other nodes) of a node for WSNs. Thus, the network is quickly disconnected or has to reconstruct a backbone. We propose a distributed algorithm to create a stable backbone by selecting the nodes with higher energy or degree as the cluster heads. This increases the overall network lifetime. Moreover, the proposed method balances energy consumption by distributing the traffic load among nodes around the cluster head. In the simulation, the proposed scheme outperforms previous clustering schemes in terms of the average and the standard deviation of residual energy or degree of backbone nodes, the average residual energy of backbone nodes after disseminating the sensed data, and the network lifetime. PMID:22454570

  20. Protein-protein docking with backbone flexibility.

    PubMed

    Wang, Chu; Bradley, Philip; Baker, David

    2007-10-19

    Computational protein-protein docking methods currently can create models with atomic accuracy for protein complexes provided that the conformational changes upon association are restricted to the side chains. However, it remains very challenging to account for backbone conformational changes during docking, and most current methods inherently keep monomer backbones rigid for algorithmic simplicity and computational efficiency. Here we present a reformulation of the Rosetta docking method that incorporates explicit backbone flexibility in protein-protein docking. The new method is based on a "fold-tree" representation of the molecular system, which seamlessly integrates internal torsional degrees of freedom and rigid-body degrees of freedom. Problems with internal flexible regions ranging from one or more loops or hinge regions to all of one or both partners can be readily treated using appropriately constructed fold trees. The explicit treatment of backbone flexibility improves both sampling in the vicinity of the native docked conformation and the energetic discrimination between near-native and incorrect models. PMID:17825317

  1. Geographic variation and genetic structure in Spotted Owls

    USGS Publications Warehouse

    Haig, Susan M.; Wagner, R.S.; Forsman, E.D.; Mullins, Thomas D.

    2001-01-01

    We examined genetic variation, population structure, and definition of conservation units in Spotted Owls (Strix occidentalis). Spotted Owls are mostly non-migratory, long-lived, socially monogamous birds that have decreased population viability due to their occupation of highly-fragmented late successional forests in western North America. To investigate potential effects of habitat fragmentation on population structure, we used random amplified polymorphic DNA (RAPD) to examine genetic variation hierarchically among local breeding areas, subregional groups, regional groups, and subspecies via sampling of 21 breeding areas (276 individuals) among the three subspecies of Spotted Owls. Data from 11 variable bands suggest a significant relationship between geographic distance among local breeding groups and genetic distance (Mantel r = 0.53, P < 0.02) although multi-dimensional scaling of three significant axes did not identify significant grouping at any hierarchical level. Similarly, neighbor-joining clustering of Manhattan distances indicated geographic structure at all levels and identified Mexican Spotted Owls as a distinct clade. RAPD analyses did not clearly differentiate Northern Spotted Owls from California Spotted Owls. Among Northern Spotted Owls, estimates of population differentiation (FST) ranged from 0.27 among breeding areas to 0.11 among regions. Concordantly, within-group agreement values estimated via multi-response permutation procedures of Jaccarda??s distances ranged from 0.22 among local sites to 0.11 among regions. Pairwise comparisons of FST and geographic distance within regions suggested only the Klamath region was in equilibrium with respect to gene flow and genetic drift. Merging nuclear data with recent mitochondrial data provides support for designation of an Evolutionary Significant Unit for Mexican Spotted Owls and two overlapping Management Units for Northern and California Spotted Owls.

  2. WDM backbone network with guaranteed performance planning

    NASA Astrophysics Data System (ADS)

    Liang, Peng; Sheng, Wang; Zhong, Xusi; Li, Lemin

    2005-11-01

    Wavelength-Division multiplexing (WDM), which allows a single fibre to carry multiple signals simultaneously, has been widely used to increase link capacity and is a promising technology in backbone transport network. But designing such WDM backbone network is hard for two reasons, one is the uncertainty of future traffic demand, the other is difficulty of planning of the backup resource for failure conditions. As a result, enormous amount of link capacity for the network has to be provided for the network. Recently, a new approach called Valiant Load-Balanced Scheme (VLBS) has been proposed to design the WDM backbone network. The network planned by Valiant Load-Balanced Scheme is insensitive to the traffic and continues to guarantee performance under a user defined number of link or node failures. In this paper, the Valiant Load-Balanced Scheme (VLBS) for backbone network planning has been studied and a new Valiant Load-Balanced Scheme has been proposed. Compared with the early work, the new Valiant Load-Balanced Scheme is much more general and can be used for the computation of the link capacity of both homogeneous and heterogeneous networks. The abbreviation for the general Valiant Load-Balanced Scheme is GVLBS. After a brief description of the VLBS, we will give the detail derivation of the GVLBS. The central concept of the derivation of GVLBS is transforming the heterogeneous network into a homogeneous network, and taking advantage of VLBS to get GVLBS. Such transformation process is described and the derivation and analysis of GVLBS for link capacity under normal and failure conditions is also given. The numerical results show that GVLBS can compute the minimum link capacity required for the heterogeneous backbone network under different conditions (normal or failure).

  3. Morphological structure and variations of lumbar plexus in human fetuses.

    PubMed

    Yasar, Soner; Kaya, Serdar; Temiz, Cağlar; Tehli, Ozkan; Kural, Cahit; Izci, Yusuf

    2014-04-01

    The objective of this study is to study the anatomy of lumbar plexus on human fetuses and to establish its morphometric characteristics and differences compared with adults. Twenty lumbar plexus of 10 human fetal cadavers in different gestational ages and genders were dissected. Lumbar spinal nerves, ganglions, and peripheral nerves were exposed. Normal anatomical structure and variations of lumbar plexus were investigated and morphometric analyses were performed. The diameters of lumbar spinal nerves increased from L1 to L4. The thickest nerve forming the plexus was femoral nerve, the thinnest was ilioinguinal nerve, the longest nerve through posterior abdominal wall was iliohypogastric nerve, and the shortest nerve was femoral nerve. Each plexus had a single furcal nerve and this arose from L4 nerve in all fetuses. No prefix or postfix plexus variation was observed. In two plexuses, L1 nerve was in the form of a single branch. Also, in two plexuses, genitofemoral nerve arose only from L2 nerve. Accessory obturator nerve was observed in four plexuses. According to these findings, the morphological pattern of the lumbar plexus in the fetus was found to be very similar to the lumbar plexus in adults. PMID:22696243

  4. The challenges and importance of structural variation detection in livestock

    PubMed Central

    Bickhart, Derek M.; Liu, George E.

    2014-01-01

    Recent studies in humans and other model organisms have demonstrated that structural variants (SVs) comprise a substantial proportion of variation among individuals of each species. Many of these variants have been linked to debilitating diseases in humans, thereby cementing the importance of refining methods for their detection. Despite progress in the field, reliable detection of SVs still remains a problem even for human subjects. Many of the underlying problems that make SVs difficult to detect in humans are amplified in livestock species, whose lower quality genome assemblies and incomplete gene annotation can often give rise to false positive SV discoveries. Regardless of the challenges, SV detection is just as important for livestock researchers as it is for human researchers, given that several productive traits and diseases have been linked to copy number variations (CNVs) in cattle, sheep, and pig. Already, there is evidence that many beneficial SVs have been artificially selected in livestock such as a duplication of the agouti signaling protein gene that causes white coat color in sheep. In this review, we will list current SV and CNV discoveries in livestock and discuss the problems that hinder routine discovery and tracking of these polymorphisms. We will also discuss the impacts of selective breeding on CNV and SV frequencies and mention how SV genotyping could be used in the future to improve genetic selection. PMID:24600474

  5. Symplectic structures related with higher order variational problems

    NASA Astrophysics Data System (ADS)

    Kijowski, Jerzy; Moreno, Giovanni

    2015-06-01

    In this paper, we derive the symplectic framework for field theories defined by higher order Lagrangians. The construction is based on the symplectic reduction of suitable spaces of iterated jets. The possibility of reducing a higher order system of partial differential equations to a constrained first-order one, the symplectic structures naturally arising in the dynamics of a first-order Lagrangian theory, and the importance of the Poincaré-Cartan form for variational problems, are all well-established facts. However, their adequate combination corresponding to higher order theories is missing in the literature. Here we obtain a consistent and truly finite-dimensional canonical formalism, as well as a higher order version of the Poincaré-Cartan form. In our exposition, the rigorous global proofs of the main results are always accompanied by their local coordinate descriptions, indispensable to work out practical examples.

  6. Altitude variations of the peak auroral emissions within auroral structures

    NASA Astrophysics Data System (ADS)

    Sangalli, L.; Partamies, N.; Gustavsson, B.

    2014-12-01

    The MIRACLE network monitors auroral activity in the Fennoscandian sector of Europe. Network stations cover the range of 55° to 57° magnetic latitude North and span two hours in magnetic local time. Some of the MIRACLE network stations include digital all-sky cameras (ASC) with overlapping field-of-views located at the latitude aurora occurs. The ASCs in this network operate at three different wavelengths: 427.8 nm (blue line), 557.7 nm (green line) and 630.0 nm (red line). These wavelengths are selected using narrow band filters. The new ASC systems are based on electron multiplying CCDs (emCCD), which allow higher time and spatial resolutions. The peak auroral emission altitude is determined using two ASC images from a station pair. Different auroral events are used to evaluate the altitude variations of the peak auroral emissions within auroral structures and its evolution in time.

  7. Altitude Variations of the Peak Auroral Emissions within Auroral Structures

    NASA Astrophysics Data System (ADS)

    Sangalli, L.

    2015-12-01

    The MIRACLE network monitors auroral activity in the Fennoscandian sector of Europe. Network stations cover the range of 55° to 57° magnetic latitude North and span two hours in magnetic local time. Some of the MIRACLE network stations include digital all-sky cameras (ASC) with overlapping field-of-views located at the latitude aurora occurs. The ASCs in this network operate at three different wavelengths: 427.8 nm (blue line), 557.7 nm (green line) and 630.0 nm (red line). These wavelengths are selected using narrow band filters. The new ASC systems are based on electron multiplying CCDs (emCCD), which allow higher time and spatial resolutions. The peak auroral emission altitude is determined using two ASC images from a station pair. Different auroral events are used to evaluate the altitude variations of the peak auroral emissions within auroral structures and its evolution in time.

  8. Extensive Natural Variation in Arabidopsis Seed Mucilage Structure

    PubMed Central

    Voiniciuc, Cătălin; Zimmermann, Eva; Schmidt, Maximilian Heinrich-Wilhelm; Günl, Markus; Fu, Lanbao; North, Helen M.; Usadel, Björn

    2016-01-01

    Hydrated Arabidopsis thaliana seeds are coated by a gelatinous layer called mucilage, which is mainly composed of cell wall polysaccharides. Since mucilage is rich in pectin, its architecture can be visualized with the ruthenium red (RR) dye. We screened the seeds of around 280 Arabidopsis natural accessions for variation in mucilage structure, and identified a large number of novel variants that differed from the Col-0 wild-type. Most of the accessions released smaller RR-stained capsules compared to the Col-0 reference. By biochemically characterizing the phenotypes of 25 of these accessions in greater detail, we discovered that distinct changes in polysaccharide structure resulted in gelatinous coatings with a deceptively similar appearance. Monosaccharide composition analysis of total mucilage extracts revealed a remarkable variation (from 50 to 200% of Col-0 levels) in the content of galactose and mannose, which are important subunits of heteromannan. In addition, most of the natural variants had altered Pontamine Fast Scarlet 4B staining of cellulose and significantly reduced birefringence of crystalline structures. This indicates that the production or organization of cellulose may be affected by the presence of different amounts of hemicellulose. Although, the accessions described in this study were primarily collected from Western Europe, they form five different phenotypic classes based on the combined results of our experiments. This suggests that polymorphisms at multiple loci are likely responsible for the observed mucilage structure. The transcription of MUCILAGE-RELATED10 (MUCI10), which encodes a key enzyme for galactoglucomannan synthesis, was severely reduced in multiple variants that phenocopied the muci10-1 insertion mutant. Although, we could not pinpoint any causal polymorphisms in this gene, constitutive expression of fluorescently-tagged MUCI10 proteins complemented the mucilage defects of a muci10-like accession. This leads us to

  9. Vertical variations in the turbulent structure over vineyards

    NASA Astrophysics Data System (ADS)

    Alfieri, J. G.; Kustas, W. P.; Prueger, J. H.; Hipps, L.

    2015-12-01

    Due to their highly-structured canopy, turbulent characteristics within and above vineyards, may not conform to those exhibited by other agricultural and natural ecosystems. As a result, the current generation of land surface models may not adequately describe the turbulent exchange of heat and moisture between the atmosphere and the surface over vineyards. Using data collected during 2014 as a part of the Grape Remote Sensing Atmospheric Profiling and Evapotranspiration Experiment (GRAPEX), an ongoing multi-agency field campaign conducted in the Central Valley of California, this study sought to characterize the variations in the turbulent structure over vineyards. Focusing on unstable daytime conditions, the study compared the turbulent structure at three above-canopy heights: 2.5 m, 3.75 m, and 8 m, agl. Both wavelet and Fourier-based spectral analysis of the wind velocity components indicates a strong tendency for the spectral peak to broaden and shift to lower frequencies as the measurement height increases. Also, beginning with the highest-frequency eddies, the turbulent structure at differing heights become increasingly decoupled as the distance between the measurements increases. In other terms, eddies contributing to a measurement at one height act independently of similarly-sized eddies at another height. As a result, the overall correlation between the turbulent flows measured at differing heights decreases exponential with increasing separation distance. While this effect was seen for all of the periods analyzed, the magnitude of the effect does appear to vary in response to the direction of the wind relative to the vineyard rows.

  10. Modeling (15)N NMR chemical shift changes in protein backbone with pressure.

    PubMed

    La Penna, Giovanni; Mori, Yoshiharu; Kitahara, Ryo; Akasaka, Kazuyuki; Okamoto, Yuko

    2016-08-28

    Nitrogen chemical shift is a useful parameter for determining the backbone three-dimensional structure of proteins. Empirical models for fast calculation of N chemical shift are improving their reliability, but there are subtle effects that cannot be easily interpreted. Among these, the effects of slight changes in hydrogen bonds, both intramolecular and with water molecules in the solvent, are particularly difficult to predict. On the other hand, these hydrogen bonds are sensitive to changes in protein environment. In this work, the change of N chemical shift with pressure for backbone segments in the protein ubiquitin is correlated with the change in the population of hydrogen bonds involving the backbone amide group. The different extent of interaction of protein backbone with the water molecules in the solvent is put in evidence. PMID:27586953

  11. Brillouin resonance broadening due to structural variations in nanoscale waveguides

    NASA Astrophysics Data System (ADS)

    Wolff, C.; Van Laer, R.; Steel, M. J.; Eggleton, B. J.; Poulton, C. G.

    2016-02-01

    We study the impact of structural variations (that is slowly varying geometry aberrations and internal strain fields) on the width and shape of the stimulated Brillouin scattering (SBS) resonance in nanoscale waveguides. We find that they lead to an inhomogeneous resonance broadening through two distinct mechanisms: firstly, the acoustic frequency is directly influenced via mechanical nonlinearities; secondly, the optical wave numbers are influenced via the opto-mechanical nonlinearity leading to an additional acoustic frequency shift via the phase-matching condition. We find that this second mechanism is proportional to the opto-mechanical coupling and, hence, related to the SBS-gain itself. It is absent in intra-mode forward SBS, while it plays a significant role in backward scattering. In backward SBS increasing the opto-acoustic overlap beyond a threshold defined by the fabrication tolerances will therefore no longer yield the expected quadratic increase in overall Stokes amplification. Finally, we illustrate in a numerical example that in backward SBS and inter-mode forward SBS the existence of two broadening mechanisms with opposite sign also opens the possibility to compensate the effect of geometry-induced broadening. Our results can be transferred to other micro- and nano-structured waveguide geometries such as photonic crystal fibres.

  12. Structural genomic variation in childhood epilepsies with complex phenotypes

    PubMed Central

    Helbig, Ingo; Swinkels, Marielle E M; Aten, Emmelien; Caliebe, Almuth; van 't Slot, Ruben; Boor, Rainer; von Spiczak, Sarah; Muhle, Hiltrud; Jähn, Johanna A; van Binsbergen, Ellen; van Nieuwenhuizen, Onno; Jansen, Floor E; Braun, Kees P J; de Haan, Gerrit-Jan; Tommerup, Niels; Stephani, Ulrich; Hjalgrim, Helle; Poot, Martin; Lindhout, Dick; Brilstra, Eva H; Møller, Rikke S; Koeleman, Bobby PC

    2014-01-01

    A genetic contribution to a broad range of epilepsies has been postulated, and particularly copy number variations (CNVs) have emerged as significant genetic risk factors. However, the role of CNVs in patients with epilepsies with complex phenotypes is not known. Therefore, we investigated the role of CNVs in patients with unclassified epilepsies and complex phenotypes. A total of 222 patients from three European countries, including patients with structural lesions on magnetic resonance imaging (MRI), dysmorphic features, and multiple congenital anomalies, were clinically evaluated and screened for CNVs. MRI findings including acquired or developmental lesions and patient characteristics were subdivided and analyzed in subgroups. MRI data were available for 88.3% of patients, of whom 41.6% had abnormal MRI findings. Eighty-eight rare CNVs were discovered in 71 out of 222 patients (31.9%). Segregation of all identified variants could be assessed in 42 patients, 11 of which were de novo. The frequency of all structural variants and de novo variants was not statistically different between patients with or without MRI abnormalities or MRI subcategories. Patients with dysmorphic features were more likely to carry a rare CNV. Genome-wide screening methods for rare CNVs may provide clues for the genetic etiology in patients with a broader range of epilepsies than previously anticipated, including in patients with various brain anomalies detectable by MRI. Performing genome-wide screens for rare CNVs can be a valuable contribution to the routine diagnostic workup in patients with a broad range of childhood epilepsies. PMID:24281369

  13. Variations in Upper Mantle Seismic Structure Across the Ethiopian Plateau

    NASA Astrophysics Data System (ADS)

    Weeraratne, D. S.; Solomon, S. C.; Nyblade, A. A.

    2006-05-01

    The Ethiopian plateau, disrupted by the Main Ethiopian Rift (MER) and adjacent to the nearby Red Sea spreading center, resides within a complex tectonic environment. We use Rayleigh wave phase velocity data from the Ethiopian Broadband Seismic Experiment to study the upper mantle seismic structure of the plateau. Dispersion curves indicate phase velocities that are significantly lower than other continental lithosphere by as much as 8% for periods between 18 and 91 s. Lateral velocity variations show a narrow low-velocity anomaly elongated in the NE-SW direction located within the rift boundaries. Phase velocities within the western and eastern plateau are ~6% higher than within the MER. Shear wave velocity inversions indicate a high-velocity lid that extends to 100 km ± 20 km depth and marks the base of the lithosphere. Azimuthal anisotropy within the western plateau is resolvable for periods up to 60 s; a 1.6% peak-to-peak amplitude gradually rotates in azimuth from NNE at short periods to NE at 60 s. This azimuthal rotation is consistent with lateral variations in the fast direction of SKS splitting studies between the rift and western plateau. The change in Rayleigh wave anisotropy at long periods indicates that the NE splitting direction observed within the western plateau may be due to a component of deep sublithospheric flow. We suggest that a transition in anisotropic fabric is controlled by the combined effects of aligned melt pockets within the MER and pre-existing Mozambique sutures at shallow lithospheric depths and asthenospheric flow parallel to plate spreading at greater depths. Our results may also be consistent with sublithospheric flow of mantle plume material that rises beneath the Ethiopian plateau and flows northeastward to the Red Sea spreading center.

  14. Backrub-like backbone simulation recapitulates natural protein conformational variability and improves mutant side-chain prediction

    PubMed Central

    Smith, Colin A.; Kortemme, Tanja

    2008-01-01

    Summary Incorporation of effective backbone sampling into protein simulation and design is an important step in increasing the accuracy of computational protein modeling. Recent analysis of high-resolution crystal structures has suggested a new model, termed backrub, to describe localized, hinge-like alternative backbone and side chain conformations observed in the crystal lattice. The model involves internal backbone rotations about axes between Cα atoms. Based on this observation, we have implemented a backrub-inspired sampling method in the Rosetta structure prediction and design program. We evaluate this model of backbone flexibility using three different tests. First, we show that Rosetta backrub simulations recapitulate the correlation between backbone and side-chain conformations in the high-resolution crystal structures upon which the model was based. As a second test of backrub sampling, we show that backbone flexibility improves the accuracy of predicting point-mutant side chain conformations over fixed backbone rotameric sampling alone. Finally, we show that backrub sampling of triosephosphate isomerase loop 6 can capture the ms/µs oscillation between the open and closed states observed in solution. Our results suggest that backrub sampling captures a sizable fraction of localized conformational changes that occur in natural proteins. Application of this simple model of backbone motions may significantly improve both protein design and atomistic simulations of localized protein flexibility. PMID:18547585

  15. Electric field induced localization phenomena in a ladder network with superlattice configuration: Effect of backbone environment

    NASA Astrophysics Data System (ADS)

    Dutta, Paramita; Maiti, Santanu K.; Karmakar, S. N.

    2014-09-01

    Electric field induced localization properties of a tight-binding ladder network in presence of backbone sites are investigated. Based on Green's function formalism we numerically calculate two-terminal transport together with density of states for different arrangements of atomic sites in the ladder and its backbone. Our results lead to a possibility of getting multiple mobility edges which essentially plays a switching action between a completely opaque to fully or partly conducting region upon the variation of system Fermi energy, and thus, support in fabricating mesoscopic or DNA-based switching devices.

  16. Variational Reconstruction of Left Cardiac Structure from CMR Images

    PubMed Central

    Wan, Min; Huang, Wei; Zhang, Jun-Mei; Zhao, Xiaodan; Tan, Ru San; Wan, Xiaofeng; Zhong, Liang

    2015-01-01

    Cardiovascular Disease (CVD), accounting for 17% of overall deaths in the USA, is the leading cause of death over the world. Advances in medical imaging techniques make the quantitative assessment of both the anatomy and function of heart possible. The cardiac modeling is an invariable prerequisite for quantitative analysis. In this study, a novel method is proposed to reconstruct the left cardiac structure from multi-planed cardiac magnetic resonance (CMR) images and contours. Routine CMR examination was performed to acquire both long axis and short axis images. Trained technologists delineated the endocardial contours. Multiple sets of two dimensional contours were projected into the three dimensional patient-based coordinate system and registered to each other. The union of the registered point sets was applied a variational surface reconstruction algorithm based on Delaunay triangulation and graph-cuts. The resulting triangulated surfaces were further post-processed. Quantitative evaluation on our method was performed via computing the overlapping ratio between the reconstructed model and the manually delineated long axis contours, which validates our method. We envisage that this method could be used by radiographers and cardiologists to diagnose and assess cardiac function in patients with diverse heart diseases. PMID:26689551

  17. Variational Reconstruction of Left Cardiac Structure from CMR Images.

    PubMed

    Wan, Min; Huang, Wei; Zhang, Jun-Mei; Zhao, Xiaodan; Tan, Ru San; Wan, Xiaofeng; Zhong, Liang

    2015-01-01

    Cardiovascular Disease (CVD), accounting for 17% of overall deaths in the USA, is the leading cause of death over the world. Advances in medical imaging techniques make the quantitative assessment of both the anatomy and function of heart possible. The cardiac modeling is an invariable prerequisite for quantitative analysis. In this study, a novel method is proposed to reconstruct the left cardiac structure from multi-planed cardiac magnetic resonance (CMR) images and contours. Routine CMR examination was performed to acquire both long axis and short axis images. Trained technologists delineated the endocardial contours. Multiple sets of two dimensional contours were projected into the three dimensional patient-based coordinate system and registered to each other. The union of the registered point sets was applied a variational surface reconstruction algorithm based on Delaunay triangulation and graph-cuts. The resulting triangulated surfaces were further post-processed. Quantitative evaluation on our method was performed via computing the overlapping ratio between the reconstructed model and the manually delineated long axis contours, which validates our method. We envisage that this method could be used by radiographers and cardiologists to diagnose and assess cardiac function in patients with diverse heart diseases. PMID:26689551

  18. AbDesign: an algorithm for combinatorial backbone design guided by natural conformations and sequences

    PubMed Central

    Lapidoth, Gideon D.; Baran, Dror; Pszolla, Gabriele M.; Norn, Christoffer; Alon, Assaf; Tyka, Michael D.; Fleishman, Sarel J.

    2016-01-01

    Computational design of protein function has made substantial progress, generating new enzymes, binders, inhibitors, and nanomaterials not previously seen in nature. However, the ability to design new protein backbones for function – essential to exert control over all polypeptide degrees of freedom – remains a critical challenge. Most previous attempts to design new backbones computed the mainchain from scratch. Here, instead, we describe a combinatorial backbone and sequence optimization algorithm called AbDesign, which leverages the large number of sequences and experimentally determined molecular structures of antibodies to construct new antibody models, dock them against target surfaces and optimize their sequence and backbone conformation for high stability and binding affinity. We used the algorithm to produce antibody designs that target the same molecular surfaces as nine natural, high-affinity antibodies; in six the backbone conformation at the core of the antibody binding surface is similar to the natural antibody targets, and in several cases sequence and sidechain conformations recapitulate those seen in the natural antibodies. In the case of an anti-lysozyme antibody, designed antibody CDRs at the periphery of the interface, such as L1 and H2, show a greater backbone conformation diversity than the CDRs at the core of the interface, and increase the binding surface area compared to the natural antibody, which could enhance affinity and specificity. PMID:25670500

  19. Conceptual Structure and Semantic Variation for Spatial Relations

    ERIC Educational Resources Information Center

    Khetarpal, Naveen Mohan

    2012-01-01

    Semantic categories across languages appear to reflect both universal conceptual tendencies and linguistic convention. To accommodate this pattern of constrained variation, many theories assume the existence of a universal conceptual space and explain cross-language variation in category extension as language-specific partitions of that space.…

  20. DNA Backbone BI/BII Distribution and Dynamics in E2 Protein-Bound Environment Determined by Molecular Dynamics Simulations.

    PubMed

    Robertson, James C; Cheatham, Thomas E

    2015-11-01

    BI and BII conformational substates in the DNA backbone typify canonical B-form DNA. The BI and BII substates are important for structural variation of DNA and have been implicated in protein-nucleic acid recognition mechanisms. Recent refinements have been made to nucleic acid force fields employed in molecular dynamics simulations that demonstrate a better ability to model the BI and BII states, leading to overall improved modeling of DNA structure and dynamics. These force field improvements have yet to be significantly demonstrated in the context of a protein-DNA system extended to long time scales. Our plan was to run molecular dynamics simulations of a well-studied protein-DNA system (E2-DNA) into the microsecond time scale and determine the ability of the force field to populate BII states in the DNA backbone consistent with dinucleotide steps crystallized in the BII conformation. The results showed that the dinucleotide steps in the E2-DNA complex with the highest BII populations from simulation trajectories corresponded to the dinucleotide steps crystallized in the BII state and that decoy BI and BII states converge to the same results within approximately one microsecond. PMID:26482568

  1. Electron Transfer Dissociation Reveals Changes in the Cleavage Frequencies of Backbone Bonds Distant to Amide-to-Ester Substitutions in Polypeptides

    NASA Astrophysics Data System (ADS)

    Hansen, Thomas A.; Jung, Hye R.; Kjeldsen, Frank

    2011-11-01

    Interrogation of electron transfer dissociation (ETD) mass spectra of peptide amide-to-ester backbone bond substituted analogues (depsipeptides) reveals substantial differences in the entire backbone cleavage frequencies. It is suggested that the point permutation of backbone bonds leads to changes in the predominant ion structures by removal/weakening of specific hydrogen bonding. ETD responds to these changes by redistributing the cleavage frequencies of the peptide backbone bonds. In comparison, no distinction between depsi-/peptide was observed using collision-activated dissociation, which is consistent with a general unfolding and elimination of structural information of these ions. These results should encourage further exploration of depsipeptides for gas-phase structural characterization.

  2. A comparison of the structures of some 2- and 3-substituted chromone derivatives: a structural study on the importance of the secondary carboxamide backbone for the inhibitory activity of MAO-B

    PubMed Central

    Gomes, Ligia R.; Low, John Nicolson; Cagide, Fernando; Gaspar, Alexandra; Borges, Fernanda

    2015-01-01

    The crystal structures of the 3-substituted tertiary chromone carboxamide derivative, C17H13NO3, N-methyl-4-oxo-N-phenyl-4H-chromene-3-carboxamide (1), and the chromone carbonyl pyrrolidine derivatives, C14H13NO3, 3-(pyrrolidine-1-carbon­yl)-4H-chromen-4-one (3) and 2-(pyrrolidine-1-carbon­yl)-4H-chromen-4-one (4) have been determined. Their structural features are discussed and compared with similar compounds namely with respect to their MAO-B inhibitory activities. The chromone carboxamide presents a –syn conformation with the aromatic rings twisted with respect to each other [the dihedral angle between the mean planes of the chromone system and the exocyclic phenyl ring is 58.48 (8)°]. The pyrrolidine derivatives also display a significant twist: the dihedral angles between the chromone system and the best plane formed by the pyrrolidine atoms are 48.9 (2) and 23.97 (12)° in (3) and (4), respectively. Compound (3) shows a short C—H⋯O intra­molecular contact forming an S(7) ring. The supra­molecular structures for each compound are defined by weak C—H⋯O hydrogen bonds, which link the mol­ecules into chains and sheets. The Cambridge Structural Database gave 45 hits for compounds with a pyrrolidinecarbonyl group. A simple statistical analysis of their geometric parameters is made in order to compare them with those of the mol­ecules determined in the present work. PMID:26594490

  3. A comparison of the structures of some 2- and 3-substituted chromone derivatives: a structural study on the importance of the secondary carboxamide backbone for the inhibitory activity of MAO-B.

    PubMed

    Gomes, Ligia R; Low, John Nicolson; Cagide, Fernando; Gaspar, Alexandra; Borges, Fernanda

    2015-11-01

    The crystal structures of the 3-substituted tertiary chromone carboxamide derivative, C17H13NO3, N-methyl-4-oxo-N-phenyl-4H-chromene-3-carboxamide (1), and the chromone carbonyl pyrrolidine derivatives, C14H13NO3, 3-(pyrrolidine-1-carbon-yl)-4H-chromen-4-one (3) and 2-(pyrrolidine-1-carbon-yl)-4H-chromen-4-one (4) have been determined. Their structural features are discussed and compared with similar compounds namely with respect to their MAO-B inhibitory activities. The chromone carboxamide presents a -syn conformation with the aromatic rings twisted with respect to each other [the dihedral angle between the mean planes of the chromone system and the exocyclic phenyl ring is 58.48 (8)°]. The pyrrolidine derivatives also display a significant twist: the dihedral angles between the chromone system and the best plane formed by the pyrrolidine atoms are 48.9 (2) and 23.97 (12)° in (3) and (4), respectively. Compound (3) shows a short C-H⋯O intra-molecular contact forming an S(7) ring. The supra-molecular structures for each compound are defined by weak C-H⋯O hydrogen bonds, which link the mol-ecules into chains and sheets. The Cambridge Structural Database gave 45 hits for compounds with a pyrrolidinecarbonyl group. A simple statistical analysis of their geometric parameters is made in order to compare them with those of the mol-ecules determined in the present work. PMID:26594490

  4. Spiral structures and regularities in magnetic field variations and auroras

    NASA Astrophysics Data System (ADS)

    Feldstein, Y. I.; Gromova, L. I.; Förster, M.; Levitin, A. E.

    2012-02-01

    The conception of spiral shaped precipitation regions, where solar corpuscles penetrate the upper atmosphere, was introduced into geophysics by C. Störmer and K. Birkeland at the beginning of the last century. Later, in the course of the XX-th century, spiral distributions were disclosed and studied in various geophysical phenomena. Most attention was devoted to spiral shapes in the analysis of regularities pertaining to the geomagnetic activity and auroras. We review the historical succession of perceptions about the number and positions of spiral shapes, that characterize the spatial-temporal distribution of magnetic disturbances. We describe the processes in the upper atmosphere, which are responsible for the appearance of spiral patterns. We considered the zones of maximal aurora frequency and of maximal particle precipitation intensity, as offered in the literature, in their connection with the spirals. We discuss the current system model, that is closely related to the spirals and that appears to be the source for geomagnetic field variations during magnetospheric substorms and storms. The currents in ionosphere and magnetosphere constitute together with field-aligned (along the geomagnetic field lines) currents (FACs) a common 3-D current system. At ionospheric heights, the westward and eastward electrojets represent characteristic elements of the current system. The westward electrojet covers the longitudinal range from the morning to the evening hours, while the eastward electrojet ranges from afternoon to near-midnight hours. The polar electrojet is positioned in the dayside sector at cusp latitudes. All these electrojets map along the magnetic field lines to certain plasma structures in the near-Earth space. The first spiral distribution of auroras was found based on observations in Antarctica for the nighttime-evening sector (N-spiral), and later in the nighttime-evening (N-spiral) and morning (M-spiral) sectors both in the Northern and Southern

  5. Computational structural variation discovery in genomes: state of the art and challenges

    NASA Astrophysics Data System (ADS)

    Osipowski, Paweł; Pawełkowicz, Magdalena; Przybecki, Zbigniew

    2014-11-01

    Identifying structural variations is crucial to obtain comprehensive knowledge on genomic differentiation. Massive data generated by present technologies determines researchers to make use of computational methods for variation discovery in genomes. Focusing on results and trying to specify challenges remained and possible solutions for the future, here we give a review of state-of-the-art methods and software utilized for structural variation discovery.

  6. Diffraction in resonant electron scattering from helical macromolecules: Effects of the DNA backbone

    SciTech Connect

    Caron, Laurent; Sanche, Leon

    2005-09-15

    We recently developed a theoretical framework to treat low-energy electron scattering from helical macromolecules. In this article, we use this framework to extend our previous model of simple base-pair scatterers, organized into the DNA structure, to include the backbone. The internal diffraction pattern due to base pairs is still present, but addition of the backbone screens the base pairs by a factor of 2. More interestingly, the effect of constructive interference on the phosphate groups within the backbone itself is seen to be strong at lower energies. We perform a calculation for electrons incident perpendicular and parallel to the axis of a fragment and find comparable electron patterns on the phosphate groups at the surface of films consisting of vertically or horizontally arranged segments relative to the substrate.

  7. Carbon backbone topology of the metabolome of a cell.

    PubMed

    Bingol, Kerem; Zhang, Fengli; Bruschweiler-Li, Lei; Brüschweiler, Rafael

    2012-05-30

    The complex metabolic makeup of a biological system, such as a cell, is a key determinant of its biological state providing unique insights into its function. Here we characterize the metabolome of a cell by a novel homonuclear (13)C 2D NMR approach applied to a nonfractionated uniformly (13)C-enriched lysate of E. coli cells and determine de novo their carbon backbone topologies that constitute the "topolome". A protocol was developed, which first identifies traces in a constant-time (13)C-(13)C TOCSY NMR spectrum that are unique for individual mixture components and then assembles for each trace the corresponding carbon-bond topology network by consensus clustering. This led to the determination of 112 topologies of unique metabolites from a single sample. The topolome is dominated by carbon topologies of carbohydrates (34.8%) and amino acids (45.5%) that can constitute building blocks of more complex structures. PMID:22540339

  8. A Native to Amyloidogenic Transition Regulated by a Backbone Trigger

    SciTech Connect

    Eakin,C.; Berman, A.; Miranker, A.

    2006-01-01

    Many polypeptides can self-associate into linear, aggregated assemblies termed amyloid fibers. High-resolution structural insights into the mechanism of fibrillogenesis are elusive owing to the transient and mixed oligomeric nature of assembly intermediates. Here, we report the conformational changes that initiate fiber formation by beta-2-microglobulin (beta2m) in dialysis-related amyloidosis. Access of beta2m to amyloidogenic conformations is catalyzed by selective binding of divalent cations. The chemical basis of this process was determined to be backbone isomerization of a conserved proline. On the basis of this finding, we designed a beta2m variant that closely adopts this intermediate state. The variant has kinetic, thermodynamic and catalytic properties consistent with its being a fibrillogenic intermediate of wild-type beta2m. Furthermore, it is stable and folded, enabling us to unambiguously determine the initiating conformational changes for amyloid assembly at atomic resolution.

  9. Morphodynamics structures induced by variations of the channel width

    NASA Astrophysics Data System (ADS)

    Duro, Gonzalo; Crosato, Alessandra; Tassi, Pablo

    2014-05-01

    In alluvial channels, forcing effects, such as a longitudinally varying width, can induce the formation of steady bars (Olesen, 1984). The type of bars that form, such as alternate, central or multiple, will mainly depend on the local flow width-to-depth ratio and on upstream conditions (Struiksma et al., 1985). The effects on bar formation of varying the channel width received attention only recently and investigations, based on flume experiments and mathematical modelling, are mostly restricted to small longitudinal sinusoidal variations of the channel width (e.g. Repetto et al., 2002; Wu and Yeh, 2005, Zolezzi et al., 2012; Frascati and Lanzoni, 2013). In this work, we analyze the variations in equilibrium bed topography in a longitudinal width-varying channel with characteristic scales of the Waal River (The Netherlands) using two different 2D depth-averaged morphodynamic models, one based on the Delft3D code and one on Telemac-Mascaret system. In particular, we explore the effects of changing the wavelength of sinusoidal width variations in a straight channel, focusing on the effects of the spatial lag between bar formation and forcing that is observed in numerical models and laboratory experiments (e.g. Crosato et al, 2011). We extend the investigations to finite width variations in which longitudinal changes of the width-to-depth ratio are such that they may affect the type of bars that become unstable (alternate, central or multiple bars). Numerical results are qualitatively validated with field observations and the resulting morphodynamic pattern is compared with the physics-based predictor of river bar modes by Crosato and Mosselman (2009). The numerical models are finally used to analyse the experimental conditions of Wu and Yeh (2005). The study should be seen as merely exploratory. The aim is to investigate possible approaches for future research aiming at assessing the effects of artificial river widening and narrowing to control bar formation in

  10. Genome-Wide Structural Variation Detection by Genome Mapping on Nanochannel Arrays

    PubMed Central

    Mak, Angel C. Y.; Lai, Yvonne Y. Y.; Lam, Ernest T.; Kwok, Tsz-Piu; Leung, Alden K. Y.; Poon, Annie; Mostovoy, Yulia; Hastie, Alex R.; Stedman, William; Anantharaman, Thomas; Andrews, Warren; Zhou, Xiang; Pang, Andy W. C.; Dai, Heng; Chu, Catherine; Lin, Chin; Wu, Jacob J. K.; Li, Catherine M. L.; Li, Jing-Woei; Yim, Aldrin K. Y.; Chan, Saki; Sibert, Justin; Džakula, Željko; Cao, Han; Yiu, Siu-Ming; Chan, Ting-Fung; Yip, Kevin Y.; Xiao, Ming; Kwok, Pui-Yan

    2016-01-01

    Comprehensive whole-genome structural variation detection is challenging with current approaches. With diploid cells as DNA source and the presence of numerous repetitive elements, short-read DNA sequencing cannot be used to detect structural variation efficiently. In this report, we show that genome mapping with long, fluorescently labeled DNA molecules imaged on nanochannel arrays can be used for whole-genome structural variation detection without sequencing. While whole-genome haplotyping is not achieved, local phasing (across >150-kb regions) is routine, as molecules from the parental chromosomes are examined separately. In one experiment, we generated genome maps from a trio from the 1000 Genomes Project, compared the maps against that derived from the reference human genome, and identified structural variations that are >5 kb in size. We find that these individuals have many more structural variants than those published, including some with the potential of disrupting gene function or regulation. PMID:26510793

  11. Historical variation of structural novelty in a natural product library.

    PubMed

    Kong, De-Xin; Guo, Ming-Yue; Xiao, Zhi-Hong; Chen, Ling-Ling; Zhang, Hong-Yu

    2011-11-01

    To evaluate the potential of natural products as novel structure suppliers, a historical analysis was performed on the structural novelty of a natural product library, viz., the Chapman & Hall/CRC Dictionary of Natural Products. The results show that although the unexplored natural product universe is still ample, it is more and more difficult to find novel agents from nature, with the discovery probability of novel structures and scaffolds being lower than 50% in the near future, which mainly results from the intrinsic redundancy of natural products and, thus, is unlikely to be reversed merely through technical progresses. PMID:22083910

  12. Impact of Temperature on Cooling Structural Variation of Forging Dies

    NASA Astrophysics Data System (ADS)

    Piesova, Marianna; Czan, Andrej

    2014-12-01

    The article is focused on the issue of die forging in the automotive industry. The cooling effect of temperature on the structure of forged die are under review. In the article, there is elaborated the analysis of theoretical knowledge in the field, focusing on die forging and experimentally proven effect of the cooling rate on the final structure of forged dies made of hypoeutectic carbon steel C56E2.

  13. Extracting the Information Backbone in Online System

    PubMed Central

    Zhang, Qian-Ming; Zeng, An; Shang, Ming-Sheng

    2013-01-01

    Information overload is a serious problem in modern society and many solutions such as recommender system have been proposed to filter out irrelevant information. In the literature, researchers have been mainly dedicated to improving the recommendation performance (accuracy and diversity) of the algorithms while they have overlooked the influence of topology of the online user-object bipartite networks. In this paper, we find that some information provided by the bipartite networks is not only redundant but also misleading. With such “less can be more” feature, we design some algorithms to improve the recommendation performance by eliminating some links from the original networks. Moreover, we propose a hybrid method combining the time-aware and topology-aware link removal algorithms to extract the backbone which contains the essential information for the recommender systems. From the practical point of view, our method can improve the performance and reduce the computational time of the recommendation system, thus improving both of their effectiveness and efficiency. PMID:23690946

  14. Toward future IP optical backbone networks

    NASA Astrophysics Data System (ADS)

    Urushidani, Shigeo

    2005-11-01

    The rapid and aggressive penetration of broadband access services such as fiber to the home (FTTH) has been accelerating the increase in IP traffic volume and new networking technologies are required in order to accommodate future traffic in a cost-effective manner. This paper overviews the advanced IP optical network architecture and technologies for very-large-scale IP backbone networks. These technologies are the key to accommodate the huge volumes of IP traffic expected and control network resources in an effective and dynamic manner. We describe advanced IP optical networking technologies which accommodate multiple service networks using multi-instance technologies, and enable multi-layer traffic engineering using virtual network topology technologies. The migration scenario is described from the existing networks to GMPLS networks; reference is made to the advanced Path Computation Element (PCE) which enables multi-layer traffic engineering and MPLS/GMPLS migration. New network concepts such as Layer 1 Virtual Private Network (L1VPN) and GMPLS interoperability issues, which are being discussed in IETF, are also described.

  15. Extracting the information backbone in online system.

    PubMed

    Zhang, Qian-Ming; Zeng, An; Shang, Ming-Sheng

    2013-01-01

    Information overload is a serious problem in modern society and many solutions such as recommender system have been proposed to filter out irrelevant information. In the literature, researchers have been mainly dedicated to improving the recommendation performance (accuracy and diversity) of the algorithms while they have overlooked the influence of topology of the online user-object bipartite networks. In this paper, we find that some information provided by the bipartite networks is not only redundant but also misleading. With such "less can be more" feature, we design some algorithms to improve the recommendation performance by eliminating some links from the original networks. Moreover, we propose a hybrid method combining the time-aware and topology-aware link removal algorithms to extract the backbone which contains the essential information for the recommender systems. From the practical point of view, our method can improve the performance and reduce the computational time of the recommendation system, thus improving both of their effectiveness and efficiency. PMID:23690946

  16. Structural Variations and Solvent Structure of r(UGGGGU) Quadruplexes Stabilized by Sr2+ Ions

    PubMed Central

    Fyfe, Alastair C.; Dunten, Pete W.; Martick, Monika M.; Scott, William G.

    2015-01-01

    Guanine-rich sequences can, under appropriate conditions, adopt a distinctive, four-stranded, helical fold known as a G-quadruplex. Interest in quadruplex folds has grown in recent years as evidence of their biological relevance has accumulated from both sequence analysis and function-specific assays. The folds are unusually stable and their formation appears to require close management to maintain cell health; regulatory failure correlates with genomic instability and a number of cancer phenotypes. Biologically relevant quadruplex folds are anticipated to form transiently in mRNA and in single-stranded, unwound DNA. To elucidate factors, including bound solvent, that contribute to the stability of RNA quadruplexes, we examine, by X-ray crystallography and small-angle X-ray scattering, the structure of a previously reported tetramolecular quadruplex, UGGGGU stabilized by Sr2+ ions. Crystal forms of the octameric assembly formed by this sequence exhibit unusually strong diffraction and anomalous signal enabling the construction of reliable models to a resolution of 0.88 Å. The solvent structure confirms hydration patterns reported for other nucleic acid helical conformations and provides support for the greater stability of RNA quadruplexes relative to DNA. Novel features detected in the octameric RNA assembly include a new crystal form, evidence of multiple conformations and structural variations in the 3′ U tetrad, including one that leads to the formation of a hydrated internal cavity. PMID:25861762

  17. Variation in the helical structure of native collagen.

    PubMed

    Orgel, Joseph P R O; Persikov, Anton V; Antipova, Olga

    2014-01-01

    The structure of collagen has been a matter of curiosity, investigation, and debate for the better part of a century. There has been a particularly productive period recently, during which much progress has been made in better describing all aspects of collagen structure. However, there remain some questions regarding its helical symmetry and its persistence within the triple-helix. Previous considerations of this symmetry have sometimes confused the picture by not fully recognizing that collagen structure is a highly complex and large hierarchical entity, and this affects and is effected by the super-coiled molecules that make it. Nevertheless, the symmetry question is not trite, but of some significance as it relates to extracellular matrix organization and cellular integration. The correlation between helical structure in the context of the molecular packing arrangement determines which parts of the amino acid sequence of the collagen fibril are buried or accessible to the extracellular matrix or the cell. In this study, we concentrate primarily on the triple-helical structure of fibrillar collagens I and II, the two most predominant types. By comparing X-ray diffraction data collected from type I and type II containing tissues, we point to evidence for a range of triple-helical symmetries being extant in the molecules native environment. The possible significance of helical instability, local helix dissociation and molecular packing of the triple-helices is discussed in the context of collagen's supramolecular organization, all of which must affect the symmetry of the collagen triple-helix. PMID:24586843

  18. Buckling of Thermoviscoelastic Structures Under Temporal and Spatial Temperature Variations

    NASA Technical Reports Server (NTRS)

    Tsuyuki, Richard; Knauss, Wolfgang G.

    1992-01-01

    The problem of lateral instability of a viscoelastic in-plane loaded structure is considered in terms of thermorheolgically simple materials. As an example of a generally in-plane loaded structure, we examine the simple column under axial load: Both cyclic loading is considered (with constant or in-phase variable temperature excursions) as well as the case of constant load in the presence of thermal gradients through the thickness of the structure. The latter case involves a continuous movement of the neutral axis from the center to the colder side and then back to the center. In both cases, temperature has a very strong effect on the instability evolution, and under in-phase thermal cycling the critical loads are reduced compared to those at constant temperatures. The primary effect of thermal gradients beyond that of thermally-induced rate accelerations is occasioned by the generation of an "initial imperfection" or "structural bowing." Because the coefficient of thermal expansion tends to be large for many polymeric materials, it it may be necessary to take special care in lay-up design of composite structures intended for use under compressive loads in high-temperature applications. Finally, the implications for the temperature sensitivities of composites to micro-instability (fiber crimping) are also apparent from the results delineated here.

  19. SPATIAL VARIATION OF THE EVOLUTION AND STRUCTURE OF THE URBAN BOUNDARY LAYER

    EPA Science Inventory

    The spatial variation of the nocturnal urban boundary layer structure and the time variation of the mixing height, the nocturnal inversion top and strength after sunrise are presented for urban sites located upwind, downwind, and near the center of the heat island and for upwind ...

  20. Variation in Narrative Structure: A Simple Text vs. an Innovative Work of Art.

    ERIC Educational Resources Information Center

    Bjorklund, Martina; Virtanen, Tuija

    The focus of this paper is the variation within the narrative type of text. Specific attention is on the variation between two rather extreme forms of narrative: simple stories written for children that may be described as stereotypical in structure, and an artistic story, "The Steppe," by A. Cexov. The view is taken that stories are comparable…

  1. Studies on cattle genomic structural variation provide insights into ruminant speciation and adaptation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomic structural variations, including segmental duplications (SD) and copy number variations (CNV), contribute significantly to individual health and disease in primates and rodents. As a part of the bovine genome annotation effort, we performed the first genome-wide analysis of SD in cattle usin...

  2. Integrating population variation and protein structural analysis to improve clinical interpretation of missense variation: application to the WD40 domain.

    PubMed

    Laskowski, Roman A; Tyagi, Nidhi; Johnson, Diana; Joss, Shelagh; Kinning, Esther; McWilliam, Catherine; Splitt, Miranda; Thornton, Janet M; Firth, Helen V; Wright, Caroline F

    2016-03-01

    We present a generic, multidisciplinary approach for improving our understanding of novel missense variants in recently discovered disease genes exhibiting genetic heterogeneity, by combining clinical and population genetics with protein structural analysis. Using six new de novo missense diagnoses in TBL1XR1 from the Deciphering Developmental Disorders study, together with population variation data, we show that the β-propeller structure of the ubiquitous WD40 domain provides a convincing way to discriminate between pathogenic and benign variation. Children with likely pathogenic mutations in this gene have severely delayed language development, often accompanied by intellectual disability, autism, dysmorphology and gastrointestinal problems. Amino acids affected by likely pathogenic missense mutations are either crucial for the stability of the fold, forming part of a highly conserved symmetrically repeating hydrogen-bonded tetrad, or located at the top face of the β-propeller, where 'hotspot' residues affect the binding of β-catenin to the TBLR1 protein. In contrast, those altered by population variation are significantly less likely to be spatially clustered towards the top face or to be at buried or highly conserved residues. This result is useful not only for interpreting benign and pathogenic missense variants in this gene, but also in other WD40 domains, many of which are associated with disease. PMID:26740553

  3. Interpretation of O K-edge EELS in zircon using a structural variation approach

    SciTech Connect

    Spence, John C.H; Jiang, Nan

    2009-12-01

    This work describes an approach to interpret the near-edge fine structure of electron energy-loss spectroscopy (EELS) of O K-edge in zircon using a structural variation method. The positions and intensities of several peaks in the O K-edge EELS spectrum are assigned to specific structural parameters. It suggests that the near-edge structures in EELS can be used to measure atomic structure changes.

  4. Two worlds collide: Image analysis methods for quantifying structural variation in cluster molecular dynamics

    SciTech Connect

    Steenbergen, K. G.; Gaston, N.

    2014-02-14

    Inspired by methods of remote sensing image analysis, we analyze structural variation in cluster molecular dynamics (MD) simulations through a unique application of the principal component analysis (PCA) and Pearson Correlation Coefficient (PCC). The PCA analysis characterizes the geometric shape of the cluster structure at each time step, yielding a detailed and quantitative measure of structural stability and variation at finite temperature. Our PCC analysis captures bond structure variation in MD, which can be used to both supplement the PCA analysis as well as compare bond patterns between different cluster sizes. Relying only on atomic position data, without requirement for a priori structural input, PCA and PCC can be used to analyze both classical and ab initio MD simulations for any cluster composition or electronic configuration. Taken together, these statistical tools represent powerful new techniques for quantitative structural characterization and isomer identification in cluster MD.

  5. Variations in aggrecan structure modulate its susceptibility to aggrecanases.

    PubMed Central

    Roughley, Peter J; Barnett, James; Zuo, Fengrong; Mort, John S

    2003-01-01

    Proteoglycan aggregates and purified aggrecan from adult and fetal bovine cartilage and adult and neonatal human cartilage were subjected to in vitro degradation by recombinant aggrecanase-1 and aggrecanase-2. The ability of the aggrecanases to cleave within the aggrecan IGD (interglobular domain) and CS2 domain (chondroitin sulphate-rich domain 2) was monitored by SDS/PAGE and immunoblotting. Aggrecanase-2 showed a similar ability to cleave within the IGD of adult and immature aggrecan, whereas aggrecanase-1 was less efficient in cleavage in the IGD of immature aggrecan, for both the bovine and the human substrates. Both aggrecanases showed a similar ability to cleave within the CS2 domain of bovine aggrecan irrespective of age, but showed a much lower ability to cleave within the CS2 domain of human aggrecan. Equivalent results were obtained whether aggrecan was present in isolation or as part of proteoglycan aggregates. When proteoglycan aggregates were used, neither aggrecanase was able to cleave link protein. Thus, for aggrecan cleavage by aggrecanases, variations in cleavage efficiency exist with respect to the species and age of the animal from which the aggrecan is derived and the type of aggrecanase being used. PMID:12859252

  6. Protein 3D Structure Computed from Evolutionary Sequence Variation

    PubMed Central

    Sheridan, Robert; Hopf, Thomas A.; Pagnani, Andrea; Zecchina, Riccardo; Sander, Chris

    2011-01-01

    The evolutionary trajectory of a protein through sequence space is constrained by its function. Collections of sequence homologs record the outcomes of millions of evolutionary experiments in which the protein evolves according to these constraints. Deciphering the evolutionary record held in these sequences and exploiting it for predictive and engineering purposes presents a formidable challenge. The potential benefit of solving this challenge is amplified by the advent of inexpensive high-throughput genomic sequencing. In this paper we ask whether we can infer evolutionary constraints from a set of sequence homologs of a protein. The challenge is to distinguish true co-evolution couplings from the noisy set of observed correlations. We address this challenge using a maximum entropy model of the protein sequence, constrained by the statistics of the multiple sequence alignment, to infer residue pair couplings. Surprisingly, we find that the strength of these inferred couplings is an excellent predictor of residue-residue proximity in folded structures. Indeed, the top-scoring residue couplings are sufficiently accurate and well-distributed to define the 3D protein fold with remarkable accuracy. We quantify this observation by computing, from sequence alone, all-atom 3D structures of fifteen test proteins from different fold classes, ranging in size from 50 to 260 residues., including a G-protein coupled receptor. These blinded inferences are de novo, i.e., they do not use homology modeling or sequence-similar fragments from known structures. The co-evolution signals provide sufficient information to determine accurate 3D protein structure to 2.7–4.8 Å Cα-RMSD error relative to the observed structure, over at least two-thirds of the protein (method called EVfold, details at http://EVfold.org). This discovery provides insight into essential interactions constraining protein evolution and will facilitate a comprehensive survey of the universe of protein

  7. Variation in the modal parameters of space structures

    NASA Technical Reports Server (NTRS)

    Crawley, Edward F.; Barlow, Mark S.; Van Schoor, Marthinus C.; Bicos, Andrew S.

    1992-01-01

    An analytic and experimental study of gravity and suspension influences on space structural test articles is presented. A modular test article including deployable, erectable, and rotary modules was assembled in three one- and two-dimensional structures. The two deployable modules utilized cable diagonal bracing rather than rigid cross members; within a bay of one of the deployable modules, the cable preload was adjustable. A friction lock was used on the alpha joint to either allow or prohibit rotary motion. Suspension systems with plunge fundamentals of 1, 2, and 5 Hz were used for ground testing to evaluate the influences of suspension stiffness. Assembly and reassembly testing was performed, as was testing on two separate shipsets at two test sites. Trends and statistical variances in modal parameters are presented as a function of force amplitude, joint preload, reassembly, shipset and suspension. Linear finite element modeling of each structure provided analytical results for 0-g unsuspended and 1-g suspended models, which are correlated with the analytical model.

  8. Mosaic structural variation in children with developmental disorders

    PubMed Central

    King, Daniel A.; Jones, Wendy D.; Crow, Yanick J.; Dominiczak, Anna F.; Foster, Nicola A.; Gaunt, Tom R.; Harris, Jade; Hellens, Stephen W.; Homfray, Tessa; Innes, Josie; Jones, Elizabeth A.; Joss, Shelagh; Kulkarni, Abhijit; Mansour, Sahar; Morris, Andrew D.; Parker, Michael J.; Porteous, David J.; Shihab, Hashem A.; Smith, Blair H.; Tatton-Brown, Katrina; Tolmie, John L.; Trzaskowski, Maciej; Vasudevan, Pradeep C.; Wakeling, Emma; Wright, Michael; Plomin, Robert; Timpson, Nicholas J.; Hurles, Matthew E.

    2015-01-01

    Delineating the genetic causes of developmental disorders is an area of active investigation. Mosaic structural abnormalities, defined as copy number or loss of heterozygosity events that are large and present in only a subset of cells, have been detected in 0.2–1.0% of children ascertained for clinical genetic testing. However, the frequency among healthy children in the community is not well characterized, which, if known, could inform better interpretation of the pathogenic burden of this mutational category in children with developmental disorders. In a case–control analysis, we compared the rate of large-scale mosaicism between 1303 children with developmental disorders and 5094 children lacking developmental disorders, using an analytical pipeline we developed, and identified a substantial enrichment in cases (odds ratio = 39.4, P-value 1.073e − 6). A meta-analysis that included frequency estimates among an additional 7000 children with congenital diseases yielded an even stronger statistical enrichment (P-value 1.784e − 11). In addition, to maximize the detection of low-clonality events in probands, we applied a trio-based mosaic detection algorithm, which detected two additional events in probands, including an individual with genome-wide suspected chimerism. In total, we detected 12 structural mosaic abnormalities among 1303 children (0.9%). Given the burden of mosaicism detected in cases, we suspected that many of the events detected in probands were pathogenic. Scrutiny of the genotypic–phenotypic relationship of each detected variant assessed that the majority of events are very likely pathogenic. This work quantifies the burden of structural mosaicism as a cause of developmental disorders. PMID:25634561

  9. Enhanced Sensitivity of Micro Mechanical Chemical Sensors Through Structural Variation

    SciTech Connect

    Harris, J.C.

    2001-04-16

    Chemical detection devices are very effective; however, their bulkiness makes them undesirable for portable applications. The next generation of chemical detectors is microscopic mechanical devices capable of measuring trace amounts of chemical vapor within the environment. The chemicals do not react directly with the detector, instead intermolecular forces cause chemicals to adhere to the surface. This surface adhesion of the chemical creates surface stress on the detectors leading to measurable movement. Modifications to the structural design of these microstructures have resulted in signal enhancement to over seven hundred percent.

  10. Insurer Market Structure and Variation in Commercial Health Care Spending

    PubMed Central

    McKellar, Michael R; Naimer, Sivia; Landrum, Mary B; Gibson, Teresa B; Chandra, Amitabh; Chernew, Michael

    2014-01-01

    Objective To examine the relationship between insurance market structure and health care prices, utilization, and spending. Data Sources Claims for 37.6 million privately insured employees and their dependents from the Truven Health Market Scan Database in 2009. Measures of insurer market structure derived from Health Leaders Inter study data. Methods Regression models are used to estimate the association between insurance market concentration and health care spending, utilization, and price, adjusting for differences in patient characteristics and other market-level traits. Results Insurance market concentration is inversely related to prices and spending, but positively related to utilization. Our results imply that, after adjusting for input price differences, a market with two equal size insurers is associated with 3.9 percent lower medical care spending per capita (p = .002) and 5.0 percent lower prices for health care services relative to one with three equal size insurers (p < .001). Conclusion Greater fragmentation in the insurance market might lead to higher prices and higher spending for care, suggesting some of the gains from insurer competition may be absorbed by higher prices for health care. Greater attention to prices and utilization in the provider market may need to accompany procompetitive insurance market strategies. PMID:24303879

  11. Genetic variation and population structure in native Americans.

    PubMed

    Wang, Sijia; Lewis, Cecil M; Jakobsson, Mattias; Ramachandran, Sohini; Ray, Nicolas; Bedoya, Gabriel; Rojas, Winston; Parra, Maria V; Molina, Julio A; Gallo, Carla; Mazzotti, Guido; Poletti, Giovanni; Hill, Kim; Hurtado, Ana M; Labuda, Damian; Klitz, William; Barrantes, Ramiro; Bortolini, Maria Cátira; Salzano, Francisco M; Petzl-Erler, Maria Luiza; Tsuneto, Luiza T; Llop, Elena; Rothhammer, Francisco; Excoffier, Laurent; Feldman, Marcus W; Rosenberg, Noah A; Ruiz-Linares, Andrés

    2007-11-01

    We examined genetic diversity and population structure in the American landmass using 678 autosomal microsatellite markers genotyped in 422 individuals representing 24 Native American populations sampled from North, Central, and South America. These data were analyzed jointly with similar data available in 54 other indigenous populations worldwide, including an additional five Native American groups. The Native American populations have lower genetic diversity and greater differentiation than populations from other continental regions. We observe gradients both of decreasing genetic diversity as a function of geographic distance from the Bering Strait and of decreasing genetic similarity to Siberians--signals of the southward dispersal of human populations from the northwestern tip of the Americas. We also observe evidence of: (1) a higher level of diversity and lower level of population structure in western South America compared to eastern South America, (2) a relative lack of differentiation between Mesoamerican and Andean populations, (3) a scenario in which coastal routes were easier for migrating peoples to traverse in comparison with inland routes, and (4) a partial agreement on a local scale between genetic similarity and the linguistic classification of populations. These findings offer new insights into the process of population dispersal and differentiation during the peopling of the Americas. PMID:18039031

  12. Genetic Variation and Population Structure in Native Americans

    PubMed Central

    Ramachandran, Sohini; Ray, Nicolas; Bedoya, Gabriel; Rojas, Winston; Parra, Maria V; Molina, Julio A; Gallo, Carla; Mazzotti, Guido; Poletti, Giovanni; Hill, Kim; Hurtado, Ana M; Labuda, Damian; Klitz, William; Barrantes, Ramiro; Bortolini, Maria Cátira; Salzano, Francisco M; Petzl-Erler, Maria Luiza; Tsuneto, Luiza T; Llop, Elena; Rothhammer, Francisco; Excoffier, Laurent; Feldman, Marcus W; Rosenberg, Noah A; Ruiz-Linares, Andrés

    2007-01-01

    We examined genetic diversity and population structure in the American landmass using 678 autosomal microsatellite markers genotyped in 422 individuals representing 24 Native American populations sampled from North, Central, and South America. These data were analyzed jointly with similar data available in 54 other indigenous populations worldwide, including an additional five Native American groups. The Native American populations have lower genetic diversity and greater differentiation than populations from other continental regions. We observe gradients both of decreasing genetic diversity as a function of geographic distance from the Bering Strait and of decreasing genetic similarity to Siberians—signals of the southward dispersal of human populations from the northwestern tip of the Americas. We also observe evidence of: (1) a higher level of diversity and lower level of population structure in western South America compared to eastern South America, (2) a relative lack of differentiation between Mesoamerican and Andean populations, (3) a scenario in which coastal routes were easier for migrating peoples to traverse in comparison with inland routes, and (4) a partial agreement on a local scale between genetic similarity and the linguistic classification of populations. These findings offer new insights into the process of population dispersal and differentiation during the peopling of the Americas. PMID:18039031

  13. Radiation safety system (RSS) backbones: Design, engineering, fabrication and installation

    SciTech Connect

    Wilmarth, J.E.; Sturrock, J.C.; Gallegos, F.R.

    1998-12-01

    The Radiation Safety System (RSS) Backbones are part of an electrical/electronic/mechanical system insuring safe access and exclusion of personnel to areas at the Los Alamos Neutron Science Center (LANSCE) accelerator. The RSS Backbones control the safety fusible beam plugs which terminate transmission of accelerated ion beams in response to predefined conditions. Any beam or access fault of the backbone inputs will cause insertion of the beam plugs in the low energy beam transport. The Backbones serve the function of tying the beam plugs to the access control systems, beam spill monitoring systems and current-level limiting systems. In some ways the Backbones may be thought of as a spinal column with beam plugs at the head and nerve centers along the spinal column. The two Linac Backbone segments and experimental area segments form a continuous cable plant over 3,500 feet from beam plugs to the tip on the longest tail. The Backbones were installed in compliance with current safety standards, such as installation of the two segments in separate conduits or tray. Monitoring for ground-faults and input wiring verification was an added enhancement to the system. The system has the capability to be tested remotely.

  14. Radiation Safety System (RSS) backbones: Design, engineering, fabrication, and installation

    SciTech Connect

    Wilmarth, J. E.; Sturrock, J. C.; Gallegos, F. R.

    1998-12-10

    The Radiation Safety System (RSS) backbones are part of an electrical/electronic/mechanical system ensuring safe access and exclusion of personnel to areas at the Los Alamos Neutron Science Center (LANSCE) accelerator. The RSS backbones control the safety-fusible beam plugs which terminate transmission of accelerated ion beams in response to predefined conditions. Any beam or access fault of the backbone inputs will cause insertion of the beam plugs in the low-energy beam transport. The backbones serve the function of tying the beam plugs to the access control systems, beam spill monitoring systems and current-level limiting systems. In some ways the backbones may be thought of as a spinal column with beam plugs at the head and nerve centers along the spinal column. The two linac backbone segments and the experimental area segments form a continuous cable plant over 3500 feet from the beam plugs to the tip on the longest tail. The backbones were installed in compliance with current safety standards, such as installation of the two segments in separate conduits or tray. Monitoring for ground-faults and input wiring verification was an added enhancement to the system. The system has the capability to be tested remotely.

  15. Radiation Safety System (RSS) backbones: Design, engineering, fabrication, and installation

    NASA Astrophysics Data System (ADS)

    Wilmarth, J. E.; Sturrock, J. C.; Gallegos, F. R.

    1998-12-01

    The Radiation Safety System (RSS) backbones are part of an electrical/electronic/mechanical system ensuring safe access and exclusion of personnel to areas at the Los Alamos Neutron Science Center (LANSCE) accelerator. The RSS backbones control the safety-fusible beam plugs which terminate transmission of accelerated ion beams in response to predefined conditions. Any beam or access fault of the backbone inputs will cause insertion of the beam plugs in the low-energy beam transport. The backbones serve the function of tying the beam plugs to the access control systems, beam spill monitoring systems and current-level limiting systems. In some ways the backbones may be thought of as a spinal column with beam plugs at the head and nerve centers along the spinal column. The two linac backbone segments and the experimental area segments form a continuous cable plant over 3500 feet from the beam plugs to the tip on the longest tail. The backbones were installed in compliance with current safety standards, such as installation of the two segments in separate conduits or tray. Monitoring for ground-faults and input wiring verification was an added enhancement to the system. The system has the capability to be tested remotely.

  16. Radiation Safety System (RSS) backbones: Design, engineering, fabrication, and installation

    SciTech Connect

    Wilmarth, J.E.; Sturrock, J.C.; Gallegos, F.R.

    1998-12-01

    The Radiation Safety System (RSS) backbones are part of an electrical/electronic/mechanical system ensuring safe access and exclusion of personnel to areas at the Los Alamos Neutron Science Center (LANSCE) accelerator. The RSS backbones control the safety-fusible beam plugs which terminate transmission of accelerated ion beams in response to predefined conditions. Any beam or access fault of the backbone inputs will cause insertion of the beam plugs in the low-energy beam transport. The backbones serve the function of tying the beam plugs to the access control systems, beam spill monitoring systems and current-level limiting systems. In some ways the backbones may be thought of as a spinal column with beam plugs at the head and nerve centers along the spinal column. The two linac backbone segments and the experimental area segments form a continuous cable plant over 3500 feet from the beam plugs to the tip on the longest tail. The backbones were installed in compliance with current safety standards, such as installation of the two segments in separate conduits or tray. Monitoring for ground-faults and input wiring verification was an added enhancement to the system. The system has the capability to be tested remotely. {copyright} {ital 1998 American Institute of Physics.}

  17. Motif-directed flexible backbone design of functional interactions

    PubMed Central

    Havranek, James J; Baker, David

    2009-01-01

    Computational protein design relies on a number of approximations to efficiently search the huge sequence space available to proteins. The fixed backbone and rotamer approximations in particular are important for formulating protein design as a discrete combinatorial optimization problem. However, the resulting coarse-grained sampling of possible side-chain terminal positions is problematic for the design of protein function, which depends on precise positioning of side-chain atoms. Although backbone flexibility can greatly increase the conformation freedom of side-chain functional groups, it is not obvious which backbone movements will generate the critical constellation of atoms responsible for protein function. Here, we report an automated method for identifying protein backbone movements that can give rise to any specified set of desired side-chain atomic placements and interactions, using protein–DNA interfaces as a model system. We use a library of previously observed protein–DNA interactions (motifs) and a rotamer-based description of side-chain conformation freedom to identify placements for the protein backbone that can give rise to a favorable side-chain interaction with DNA. We describe a tree-search algorithm for identifying those combinations of interactions from the library that can be realized with minimal perturbation of the protein backbone. We compare the efficiency of this method with the alternative approach of building and screening alternate backbone conformations. PMID:19472357

  18. Population Structure Shapes Copy Number Variation in Malaria Parasites.

    PubMed

    Cheeseman, Ian H; Miller, Becky; Tan, John C; Tan, Asako; Nair, Shalini; Nkhoma, Standwell C; De Donato, Marcos; Rodulfo, Hectorina; Dondorp, Arjen; Branch, Oralee H; Mesia, Lastenia Ruiz; Newton, Paul; Mayxay, Mayfong; Amambua-Ngwa, Alfred; Conway, David J; Nosten, François; Ferdig, Michael T; Anderson, Tim J C

    2016-03-01

    If copy number variants (CNVs) are predominantly deleterious, we would expect them to be more efficiently purged from populations with a large effective population size (Ne) than from populations with a small Ne. Malaria parasites (Plasmodium falciparum) provide an excellent organism to examine this prediction, because this protozoan shows a broad spectrum of population structures within a single species, with large, stable, outbred populations in Africa, small unstable inbred populations in South America and with intermediate population characteristics in South East Asia. We characterized 122 single-clone parasites, without prior laboratory culture, from malaria-infected patients in seven countries in Africa, South East Asia and South America using a high-density single-nucleotide polymorphism/CNV microarray. We scored 134 high-confidence CNVs across the parasite exome, including 33 deletions and 102 amplifications, which ranged in size from <500 bp to 59 kb, as well as 10,107 flanking, biallelic single-nucleotide polymorphisms. Overall, CNVs were rare, small, and skewed toward low frequency variants, consistent with the deleterious model. Relative to African and South East Asian populations, CNVs were significantly more common in South America, showed significantly less skew in allele frequencies, and were significantly larger. On this background of low frequency CNV, we also identified several high-frequency CNVs under putative positive selection using an FST outlier analysis. These included known adaptive CNVs containing rh2b and pfmdr1, and several other CNVs (e.g., DNA helicase and three conserved proteins) that require further investigation. Our data are consistent with a significant impact of genetic structure on CNV burden in an important human pathogen. PMID:26613787

  19. Population Structure Shapes Copy Number Variation in Malaria Parasites

    PubMed Central

    Cheeseman, Ian H.; Miller, Becky; Tan, John C.; Tan, Asako; Nair, Shalini; Nkhoma, Standwell C.; De Donato, Marcos; Rodulfo, Hectorina; Dondorp, Arjen; Branch, Oralee H.; Mesia, Lastenia Ruiz; Newton, Paul; Mayxay, Mayfong; Amambua-Ngwa, Alfred; Conway, David J.; Nosten, François; Ferdig, Michael T.; Anderson, Tim J. C.

    2016-01-01

    If copy number variants (CNVs) are predominantly deleterious, we would expect them to be more efficiently purged from populations with a large effective population size (Ne) than from populations with a small Ne. Malaria parasites (Plasmodium falciparum) provide an excellent organism to examine this prediction, because this protozoan shows a broad spectrum of population structures within a single species, with large, stable, outbred populations in Africa, small unstable inbred populations in South America and with intermediate population characteristics in South East Asia. We characterized 122 single-clone parasites, without prior laboratory culture, from malaria-infected patients in seven countries in Africa, South East Asia and South America using a high-density single-nucleotide polymorphism/CNV microarray. We scored 134 high-confidence CNVs across the parasite exome, including 33 deletions and 102 amplifications, which ranged in size from <500 bp to 59 kb, as well as 10,107 flanking, biallelic single-nucleotide polymorphisms. Overall, CNVs were rare, small, and skewed toward low frequency variants, consistent with the deleterious model. Relative to African and South East Asian populations, CNVs were significantly more common in South America, showed significantly less skew in allele frequencies, and were significantly larger. On this background of low frequency CNV, we also identified several high-frequency CNVs under putative positive selection using an FST outlier analysis. These included known adaptive CNVs containing rh2b and pfmdr1, and several other CNVs (e.g., DNA helicase and three conserved proteins) that require further investigation. Our data are consistent with a significant impact of genetic structure on CNV burden in an important human pathogen. PMID:26613787

  20. Genomic Heterogeneity and Structural Variation in Soybean Near Isogenic Lines

    PubMed Central

    Stec, Adrian O.; Bhaskar, Pudota B.; Bolon, Yung-Tsi; Nolan, Rebecca; Shoemaker, Randy C.; Vance, Carroll P.; Stupar, Robert M.

    2013-01-01

    Near isogenic lines (NILs) are a critical genetic resource for the soybean research community. The ability to identify and characterize the genes driving the phenotypic differences between NILs is limited by the degree to which differential genetic introgressions can be resolved. Furthermore, the genetic heterogeneity extant among NIL sub-lines is an unaddressed research topic that might have implications for how genomic and phenotypic data from NILs are utilized. In this study, a recently developed high-resolution comparative genomic hybridization (CGH) platform was used to investigate the structure and diversity of genetic introgressions in two classical soybean NIL populations, respectively varying in protein content and iron deficiency chlorosis (IDC) susceptibility. There were three objectives: assess the capacity for CGH to resolve genomic introgressions, identify introgressions that are heterogeneous among NIL sub-lines, and associate heterogeneous introgressions with susceptibility to IDC. Using the CGH approach, introgression boundaries were refined and previously unknown introgressions were revealed. Furthermore, heterogeneous introgressions were identified within seven sub-lines of the IDC NIL “IsoClark.” This included three distinct introgression haplotypes linked to the major iron susceptible locus on chromosome 03. A phenotypic assessment of the seven sub-lines did not reveal any differences in IDC susceptibility, indicating that the genetic heterogeneity among the lines does not have a significant impact on the primary NIL phenotype. PMID:23630538

  1. Population-based structural variation discovery with Hydra-Multi

    PubMed Central

    Lindberg, Michael R.; Hall, Ira M.; Quinlan, Aaron R.

    2015-01-01

    Summary: Current strategies for SNP and INDEL discovery incorporate sequence alignments from multiple individuals to maximize sensitivity and specificity. It is widely accepted that this approach also improves structural variant (SV) detection. However, multisample SV analysis has been stymied by the fundamental difficulties of SV calling, e.g. library insert size variability, SV alignment signal integration and detecting long-range genomic rearrangements involving disjoint loci. Extant tools suffer from poor scalability, which limits the number of genomes that can be co-analyzed and complicates analysis workflows. We have developed an approach that enables multisample SV analysis in hundreds to thousands of human genomes using commodity hardware. Here, we describe Hydra-Multi and measure its accuracy, speed and scalability using publicly available datasets provided by The 1000 Genomes Project and by The Cancer Genome Atlas (TCGA). Availability and implementation: Hydra-Multi is written in C++ and is freely available at https://github.com/arq5x/Hydra. Contact: aaronquinlan@gmail.com or ihall@genome.wustl.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25527832

  2. Experimental investigation of crustacean swimming with variation of limb structures

    NASA Astrophysics Data System (ADS)

    Lai, Hong Kuan; Samaee, Milad; Donnell, Geoffrey; Santhanakrishnan, Arvind; Guy, Robert; Lewis, Timothy

    2015-11-01

    Crustaceans such as crayfish and krill swim by rhythmically paddling a set of four to five limbs (known as swimmerets or pleopods) originating from their abdomen. The limb motion in these animals has been observed to follow tail-to-head metachronal wave pattern with an approximate quarter-period inter-limb phase difference. The goal of this study is to investigate the hydrodynamics of this swimming mechanism as a function of inter-limb phase difference, inclusion of hinges in the limbs, and Reynolds number (Re). 2D PIV measurements were conducted on a scaled robotic model of metachronal paddling, consisting of a rectangular tank fitted with stepper motors coupled to a four-bar linkage that actuated four paddles immersed in water-glycerin fluid medium. The inter-limb phase difference was varied from 0% (synchronous paddling) through 50% across Re range of O(10-1000). Two types of limb models were used, including a simple flat plate and a `split-paddle' structure with two flat plates connected halfway with hinges. The results of the study show that limb models with hinges generated increased horizontal (thrust-producing direction) fluid velocity compared to the simple flat plate paddles, suggesting that asymmetry between power and return strokes is important to augment thrust.

  3. On the relationship between NMR-derived amide order parameters and protein backbone entropy changes

    PubMed Central

    Sharp, Kim A.; O’Brien, Evan; Kasinath, Vignesh; Wand, A. Joshua

    2015-01-01

    Molecular dynamics simulations are used to analyze the relationship between NMR-derived squared generalized order parameters of amide NH groups and backbone entropy. Amide order parameters (O2NH) are largely determined by the secondary structure and average values appear unrelated to the overall flexibility of the protein. However, analysis of the more flexible subset (O2NH < 0.8) shows that these report both on the local flexibility of the protein and on a different component of the conformational entropy than that reported by the side chain methyl axis order parameters, O2axis. A calibration curve for backbone entropy vs. O2NH is developed which accounts for both correlations between amide group motions of different residues, and correlations between backbone and side chain motions. This calibration curve can be used with experimental values of O2NH changes obtained by NMR relaxation measurements to extract backbone entropy changes, e.g. upon ligand binding. In conjunction with our previous calibration for side chain entropy derived from measured O2axis values this provides a prescription for determination of the total protein conformational entropy changes from NMR relaxation measurements. PMID:25739366

  4. Structural and regulatory variation of phosphoglucomutase in rainbow trout.

    PubMed

    Allendorf, F W; Leary, R F; Knudsen, K L

    1983-01-01

    The results of inheritance experiments with allozymic variants indicate that two pairs of duplicate loci encode PGM in rainbow trout. Two of the loci (Pgm-3,4) share five electromorphs and are highly polymorphic. The large number of phenotypes and instability of these isozymes make them difficult to score in population studies. The other pair of duplicate loci (Pgm1 and Pgm2) have diverged both structurally and in their patterns of tissue-specific expression. We have detected four electromorphs at Pgm2; this locus is expressed approximately equally in all tissues examined. Two electromorphs and a null allele have been detected at Pgm1. PGM1 activity is greatest in skeletal muscle, heart, and brain; only weak activity, if any, is detectable in liver, eye, stomach, and kidney. Ten percent of the trout from the Arlee strain have a greater than 100-fold increase in the expression of Pgm1 in the liver but have normal expression of this locus in other tissues. Results of genetic crosses are consistent with a single regulatory gene (Pgm1-t) with additive inheritance being responsible for the differences in liver PGM1 activity. The allele responsible for the expression PGM1 in the liver is rare in rainbow trout and is apparently a recent mutation. The presence of PGM1 liver activity has a variety of phenotypic effects that are likely to be of adaptive significance. Embryos with liver PGM1 activity develop more quickly than their full-sibs lacking activity. This difference apparently results from increased flux through glycolysis in embryos with liver PGM1 activity while they are dependent on the yolk for energy. The more rapidly developing individuals begin exogenous feeding earlier and obtain a size advantage that is maintained until sexual maturity. This size advantage also produces a tendency for earlier age of first sexual maturity. Fish with liver PGM1 activity are also more developmentally buffered, as indicated by less fluctuating asymmetry of five meristic traits

  5. Subsurface hydrographic structures and the temporal variations of Aleutian eddies

    NASA Astrophysics Data System (ADS)

    Saito, Rui; Yasuda, Ichiro; Komatsu, Kosei; Ishiyama, Hiromu; Ueno, Hiromichi; Onishi, Hiroji; Setou, Takeshi; Shimizu, Manabu

    2016-05-01

    Aleutian eddies are mesoscale anticyclonic eddies formed within the Alaskan Stream region between 180° meridian and 170° E south of the Aleutian Islands. They propagate southwestward after the isolation from the Alaskan Stream and pass through the Western Subarctic Gyre. We compared hydrographic structures of three Aleutian eddies observed during summer, west of 170° E (Eddy A) and east of 170° E (Eddies B and C). In each eddy, a subsurface dichothermal water (3.0-4.0 °C) was observed above a subsurface mesothermal water (4.0-4.5 °C). The minimum temperature in the dichothermal water at around a depth of 100 m was colder in Eddy A (2.8 °C) than in Eddies B and C (3.0-3.2 °C). This difference could be ascribed to wintertime cooling and influence of surrounding waters during spring warming period. The wintertime cooling makes the dichothermal water colder for eddies isolated from the Alaskan Stream region for a longer time. Particle-tracking experiments using re-analysis products from a data-assimilative eddy resolving ocean model suggested that the dichothermal water within Eddy A was cooled by the entrainment of surrounding colder water even during the spring warming period. The mesothermal waters at depth around 250 m demonstrated similarity among the observed eddies, and the maximum temperature in the mesothermal water within Eddy A (4.3 °C) was close to that of Eddies B and C (4.2 °C) in the in situ observations. These results indicated that the dichothermal water of Aleutian eddies modifies over time, whereas the mesothermal water maintains the original feature as they propagate southwestward from the Alaskan Stream region to the Western Subarctic Gyre.

  6. Towards Structural Analysis of Audio Recordings in the Presence of Musical Variations

    NASA Astrophysics Data System (ADS)

    Müller, Meinard; Kurth, Frank

    2006-12-01

    One major goal of structural analysis of an audio recording is to automatically extract the repetitive structure or, more generally, the musical form of the underlying piece of music. Recent approaches to this problem work well for music, where the repetitions largely agree with respect to instrumentation and tempo, as is typically the case for popular music. For other classes of music such as Western classical music, however, musically similar audio segments may exhibit significant variations in parameters such as dynamics, timbre, execution of note groups, modulation, articulation, and tempo progression. In this paper, we propose a robust and efficient algorithm for audio structure analysis, which allows to identify musically similar segments even in the presence of large variations in these parameters. To account for such variations, our main idea is to incorporate invariance at various levels simultaneously: we design a new type of statistical features to absorb microvariations, introduce an enhanced local distance measure to account for local variations, and describe a new strategy for structure extraction that can cope with the global variations. Our experimental results with classical and popular music show that our algorithm performs successfully even in the presence of significant musical variations.

  7. Backbone dependency further improves side chain prediction efficiency in the Energy-based Conformer Library (bEBL).

    PubMed

    Subramaniam, Sabareesh; Senes, Alessandro

    2014-11-01

    Side chain optimization is an integral component of many protein modeling applications. In these applications, the conformational freedom of the side chains is often explored using libraries of discrete, frequently occurring conformations. Because side chain optimization can pose a computationally intensive combinatorial problem, the nature of these conformer libraries is important for ensuring efficiency and accuracy in side chain prediction. We have previously developed an innovative method to create a conformer library with enhanced performance. The Energy-based Library (EBL) was obtained by analyzing the energetic interactions between conformers and a large number of natural protein environments from crystal structures. This process guided the selection of conformers with the highest propensity to fit into spaces that should accommodate a side chain. Because the method requires a large crystallographic data-set, the EBL was created in a backbone-independent fashion. However, it is well established that side chain conformation is strongly dependent on the local backbone geometry, and that backbone-dependent libraries are more efficient in side chain optimization. Here we present the backbone-dependent EBL (bEBL), whose conformers are independently sorted for each populated region of Ramachandran space. The resulting library closely mirrors the local backbone-dependent distribution of side chain conformation. Compared to the EBL, we demonstrate that the bEBL uses fewer conformers to produce similar side chain prediction outcomes, thus further improving performance with respect to the already efficient backbone-independent version of the library. PMID:25212195

  8. Calculus structure on the Lie conformal algebra complex and the variational complex

    SciTech Connect

    De Sole, Alberto; Hekmati, Pedram; Kac, Victor G.

    2011-05-15

    We construct a calculus structure on the Lie conformal algebra cochain complex. By restricting to degree one chains, we recover the structure of a g-complex introduced in [A. De Sole and V. G. Kac, Commun. Math. Phys. 292, 667 (2009)]. A special case of this construction is the variational calculus, for which we provide explicit formulas.

  9. Variation of form and dimension for minimum weight design of continuous structures

    NASA Astrophysics Data System (ADS)

    Berkes, Uwe-Laszlo

    1987-01-01

    A method for minimum weight design of arbitrary loaded continuous structures is outlined. The optimization algorithm is controlled by a fast fully stressed design procedure and the structure stress-strain behavior is computed by the finite element code. Both are completed by pre and postprocessors. To reach the minimum weight design two tasks are carried out: dimension variation in general elementwise thickness adaption to the stress limits; and form variation by element reduction in the finite element set. For comparison of the convergence behavior and accuracy of this code, results are compared with Michell reference structures and their analytic solutions. The method shows fast convergence and reaches the theoretical optimum efficiently.

  10. Bond distances in polypeptide backbones depend on the local conformation.

    PubMed

    Improta, Roberto; Vitagliano, Luigi; Esposito, Luciana

    2015-06-01

    By combining quantum-mechanical analysis of small model peptides and statistical surveys of high-resolution protein structures, a systematic conformational dependence of bond lengths in polypeptide backbones has been unveiled which involves both the peptide bond (C-O and C-N) and those bonds centred on the C(α) atom. All of these bond lengths indeed display a systematic variability in the ψ angle according to both calculations and surveys of protein structures. The overall agreement between the computed and the statistical data suggests that these trends are essentially driven by local effects. The dependence of C(α) distances on ψ is governed by interactions between the σ system of the C(α) moiety and the C-O π system of the peptide bond. Maximum and minimum values for each bond distance are found for conformations with the specific bond perpendicular and parallel to the adjacent CONH peptide plane, respectively. On the other hand, the variability of the C-O and C-N distances is related to the strength of the interactions between the lone pair of the N atom and the C-O π* system, which is modulated by the ψ angle. The C-O and C-N distances are related but their trends are not strictly connected to peptide-bond planarity, although a correlation amongst all of these parameters is expected on the basis of the classical resonance model. PMID:26057667

  11. Genotypic variation in foundation species generates network structure that may drive community dynamics and evolution.

    PubMed

    Lau, Matthew K; Keith, Arthur R; Borrett, Stuart R; Shuster, Stephen M; Whitham, Thomas G

    2016-03-01

    Although genetics in a single species is known to impact whole communities, little is known about how genetic variation influences species interaction networks in complex ecosystems. Here, we examine the interactions in a community of arthropod species on replicated genotypes (clones) of a foundation tree species, Populus angustifolia James (narrowleaf cottonwood), in a long-term, common garden experiment using a bipartite "genotype-species" network perspective. We combine this empirical work with a simulation experiment designed to further investigate how variation among individual tree genotypes can impact network structure. Three findings emerged: (1) the empirical "genotype-species network" exhibited significant network structure with modularity being greater than the highly conservative null model; (2) as would be expected given a modular network structure, the empirical network displayed significant positive arthropod co-occurrence patterns; and (3) furthermore, the simulations of "genotype-species" networks displayed variation in network structure, with modularity in particular clearly increasing, as genotypic variation increased. These results support the conclusion that genetic variation in a single species contributes to the structure of ecological interaction networks, which could influence eco-ogical dynamics (e.g., assembly and stability) and evolution in a community context. PMID:27197399

  12. Temporal variations in internal tide multimodal structure on the continental shelf, South China Sea

    NASA Astrophysics Data System (ADS)

    Gao, Dalu; Jin, Guangzhen; Lü, Xianqing

    2016-04-01

    Temporal variations in multimodal structures of diurnal (D 1) and semidiurnal (D 2) internal tides were investigated on the continental slope of the Dongsha Plateau, based on 2-month moored acoustic Doppler current profiler observations. Harmonic analysis indicated that the D 1 components (K 1 and O 1) dominated the internal tide field. The vertical structure of the K 1 constituent presented a first-mode structure while the M 2 constituent seemed to exhibit a high-mode structure. Amplitude spectra analysis of the current data revealed differences in baroclinic current amplitudes between different water depths. Temporal variations in modal structures ware analyzed, based on the D 1 and D 2 baroclinic tides extracted from the baroclinic velocity field with band-pass filters. Analysis showed that the magnitude of the D 1 internal tide current was much larger than the D 2 current, and temporal variations in the modal structure of the D 1 internal tide occurred on an approximately fortnightly cycle. The EOF analyses revealed temporal transformation of multimodal structures for D 1 and D 2 internal tides. The enhancement of the D 1 internal tide was mainly due to the superposition of K 1 and O 1, according to the temporal variation of coherent kinetic energy.

  13. Precise colocalization of interacting structural and pigmentary elements generates extensive color pattern variation in Phelsuma lizards

    PubMed Central

    2013-01-01

    Background Color traits in animals play crucial roles in thermoregulation, photoprotection, camouflage, and visual communication, and are amenable to objective quantification and modeling. However, the extensive variation in non-melanic pigments and structural colors in squamate reptiles has been largely disregarded. Here, we used an integrated approach to investigate the morphological basis and physical mechanisms generating variation in color traits in tropical day geckos of the genus Phelsuma. Results Combining histology, optics, mass spectrometry, and UV and Raman spectroscopy, we found that the extensive variation in color patterns within and among Phelsuma species is generated by complex interactions between, on the one hand, chromatophores containing yellow/red pteridine pigments and, on the other hand, iridophores producing structural color by constructive interference of light with guanine nanocrystals. More specifically, we show that 1) the hue of the vivid dorsolateral skin is modulated both by variation in geometry of structural, highly ordered narrowband reflectors, and by the presence of yellow pigments, and 2) that the reflectivity of the white belly and of dorsolateral pigmentary red marks, is increased by underlying structural disorganized broadband reflectors. Most importantly, these interactions require precise colocalization of yellow and red chromatophores with different types of iridophores, characterized by ordered and disordered nanocrystals, respectively. We validated these results through numerical simulations combining pigmentary components with a multilayer interferential optical model. Finally, we show that melanophores form dark lateral patterns but do not significantly contribute to variation in blue/green or red coloration, and that changes in the pH or redox state of pigments provide yet another source of color variation in squamates. Conclusions Precisely colocalized interacting pigmentary and structural elements generate extensive

  14. High Density LD-Based Structural Variations Analysis in Cattle Genome

    PubMed Central

    Salomon-Torres, Ricardo; Matukumalli, Lakshmi K.; Van Tassell, Curtis P.; Villa-Angulo, Carlos; Gonzalez-Vizcarra, Víctor M.; Villa-Angulo, Rafael

    2014-01-01

    Genomic structural variations represent an important source of genetic variation in mammal genomes, thus, they are commonly related to phenotypic expressions. In this work, ∼770,000 single nucleotide polymorphism genotypes from 506 animals from 19 cattle breeds were analyzed. A simple LD-based structural variation was defined, and a genome-wide analysis was performed. After applying some quality control filters, for each breed and each chromosome we calculated the linkage disequilibrium (r2) of short range (≤100 Kb). We sorted SNP pairs by distance and obtained a set of LD means (called the expected means) using bins of 5 Kb. We identified 15,246 segments of at least 1 Kb, among the 19 breeds, consisting of sets of at least 3 adjacent SNPs so that, for each SNP, r2 within its neighbors in a 100 Kb range, to the right side of that SNP, were all bigger than, or all smaller than, the corresponding expected mean, and their P-value were significant after a Benjamini-Hochberg multiple testing correction. In addition, to account just for homogeneously distributed regions we considered only SNPs having at least 15 SNP neighbors within 100 Kb. We defined such segments as structural variations. By grouping all variations across all animals in the sample we defined 9,146 regions, involving a total of 53,137 SNPs; representing the 6.40% (160.98 Mb) from the bovine genome. The identified structural variations covered 3,109 genes. Clustering analysis showed the relatedness of breeds given the geographic region in which they are evolving. In summary, we present an analysis of structural variations based on the deviation of the expected short range LD between SNPs in the bovine genome. With an intuitive and simple definition based only on SNPs data it was possible to discern closeness of breeds due to grouping by geographic region in which they are evolving. PMID:25050984

  15. Base-pairing potential identified by in vitro selection predicts the kinked RNA backbone observed in the crystal structure of the alfalfa mosaic virus RNA-coat protein complex.

    PubMed

    Boyce, Michael; Scott, Felicia; Guogas, Laura M; Gehrke, Lee

    2006-01-01

    The three-dimensional structure of the 3' terminus of alfalfa mosaic virus RNA in complex with an amino-terminal coat protein peptide revealed an unusual RNA fold with inter-AUGC basepairing stabilized by key arginine residues (Guogas, et al., 2004). To probe viral RNA interactions with the full-length coat protein, we have used in vitro genetic selection to characterize potential folding patterns among RNAs isolated from a complex randomized pool. Nitrocellulose filter retention, electrophoretic mobility bandshift analysis, and hydroxyl radical footprinting techniques were used to define binding affinities and to localize the potential RNA-protein interaction sites. Minimized binding sites were identified that included both the randomized domain and a portion of the constant regions of the selected RNAs. The selected RNAs, identified by their ability to bind full-length coat protein, have the potential to form the same unusual inter-AUGC Watson-Crick base pairs observed in the crystal structure, although the primary sequences diverge from the wild-type RNA. A constant feature of both the wild-type RNA and the selected RNAs is a G ribonucleotide in the third position of an AUGC-like repeat. Competitive binding assays showed that substituting adenosine for the constant guanosine in either the wild-type or selected RNAs impaired coat protein binding. These data suggest that the interactions observed in the RNA-peptide structure are likely recapitulated when the full-length protein binds. Further, the results underscore the power of in vitro genetic selection for probing RNA-protein structure and function. PMID:16312015

  16. Rare Variation Facilitates Inferences of Fine-Scale Population Structure in Humans

    PubMed Central

    O’Connor, Timothy D.; Fu, Wenqing; Mychaleckyj, Josyf C.; Logsdon, Benjamin; Auer, Paul; Carlson, Christopher S.; Leal, Suzanne M.; Smith, Joshua D.; Rieder, Mark J.; Bamshad, Michael J.; Nickerson, Deborah A.; Akey, Joshua M.

    2015-01-01

    Understanding the genetic structure of human populations has important implications for the design and interpretation of disease mapping studies and reconstructing human evolutionary history. To date, inferences of human population structure have primarily been made with common variants. However, recent large-scale resequencing studies have shown an abundance of rare variation in humans, which may be particularly useful for making inferences of fine-scale population structure. To this end, we used an information theory framework and extensive coalescent simulations to rigorously quantify the informativeness of rare and common variation to detect signatures of fine-scale population structure. We show that rare variation affords unique insights into patterns of recent population structure. Furthermore, to empirically assess our theoretical findings, we analyzed high-coverage exome sequences in 6,515 European and African American individuals. As predicted, rare variants are more informative than common polymorphisms in revealing a distinct cluster of European–American individuals, and subsequent analyses demonstrate that these individuals are likely of Ashkenazi Jewish ancestry. Our results provide new insights into the population structure using rare variation, which will be an important factor to account for in rare variant association studies. PMID:25415970

  17. ViVar: A Comprehensive Platform for the Analysis and Visualization of Structural Genomic Variation

    PubMed Central

    Sante, Tom; Vergult, Sarah; Volders, Pieter-Jan; Kloosterman, Wigard P.; Trooskens, Geert; De Preter, Katleen; Dheedene, Annelies; Speleman, Frank; De Meyer, Tim; Menten, Björn

    2014-01-01

    Structural genomic variations play an important role in human disease and phenotypic diversity. With the rise of high-throughput sequencing tools, mate-pair/paired-end/single-read sequencing has become an important technique for the detection and exploration of structural variation. Several analysis tools exist to handle different parts and aspects of such sequencing based structural variation analyses pipelines. A comprehensive analysis platform to handle all steps, from processing the sequencing data, to the discovery and visualization of structural variants, is missing. The ViVar platform is built to handle the discovery of structural variants, from Depth Of Coverage analysis, aberrant read pair clustering to split read analysis. ViVar provides you with powerful visualization options, enables easy reporting of results and better usability and data management. The platform facilitates the processing, analysis and visualization, of structural variation based on massive parallel sequencing data, enabling the rapid identification of disease loci or genes. ViVar allows you to scale your analysis with your work load over multiple (cloud) servers, has user access control to keep your data safe and is easy expandable as analysis techniques advance. URL: https://www.cmgg.be/vivar/ PMID:25503062

  18. Adaptive potential of genomic structural variation in human and mammalian evolution.

    PubMed

    Radke, David W; Lee, Charles

    2015-09-01

    Because phenotypic innovations must be genetically heritable for biological evolution to proceed, it is natural to consider new mutation events as well as standing genetic variation as sources for their birth. Previous research has identified a number of single-nucleotide polymorphisms that underlie a subset of adaptive traits in organisms. However, another well-known class of variation, genomic structural variation, could have even greater potential to produce adaptive phenotypes, due to the variety of possible types of alterations (deletions, insertions, duplications, among others) at different genomic positions and with variable lengths. It is from these dramatic genomic alterations, and selection on their phenotypic consequences, that adaptations leading to biological diversification could be derived. In this review, using studies in humans and other mammals, we highlight examples of how phenotypic variation from structural variants might become adaptive in populations and potentially enable biological diversification. Phenotypic change arising from structural variants will be described according to their immediate effect on organismal metabolic processes, immunological response and physical features. Study of population dynamics of segregating structural variation can therefore provide a window into understanding current and historical biological diversification. PMID:26003631

  19. The Inherent Conformational Preferences of Glutamine-Containing Peptides: the Role for Side-Chain Backbone Hydrogen Bonds

    NASA Astrophysics Data System (ADS)

    Walsh, Patrick S.; McBurney, Carl; Gellman, Samuel H.; Zwier, Timothy S.

    2015-06-01

    Glutamine is widely known to be found in critical regions of peptides which readily fold into amyloid fibrils, the structures commonly associated with Alzheimer's disease and glutamine repeat diseases such as Huntington's disease. Building on previous single-conformation data on Gln-containing peptides containing an aromatic cap on the N-terminus (Z-Gln-OH and Z-Gln-NHMe), we present here single-conformation UV and IR spectra of Ac-Gln-NHBn and Ac-Ala-Gln-NHBn, with its C-terminal benzyl cap. These results point towards side-chain to backbone hydrogen bonds dominating the structures observed in the cold, isolated environment of a molecular beam. We have identified and assigned three main conformers for Ac-Gln-NHBn all involving primary side-chain to backbone interactions. Ac-Ala-Gln-NHBn extends the peptide chain by one amino acid, but affords an improvement in the conformational flexibility. Despite this increase in the flexibility, only a single conformation is observed in the gas-phase: a structure which makes use of both side-chain-to-backbone and backbone-to-backbone hydrogen bonds.

  20. Incorporating backbone flexibility in MedusaDock improves ligand-binding pose prediction in the CSAR2011 docking benchmark.

    PubMed

    Ding, Feng; Dokholyan, Nikolay V

    2013-08-26

    Solution of the structures of ligand-receptor complexes via computational docking is an integral step in many structural modeling efforts as well as in rational drug discovery. A major challenge in ligand-receptor docking is the modeling of both receptor and ligand flexibilities in order to capture receptor conformational changes induced by ligand binding. In the molecular docking suite MedusaDock, both ligand and receptor side chain flexibilities are modeled simultaneously with sets of discrete rotamers, where the ligand rotamer library is generated "on the fly" in a stochastic manner. Here, we introduce backbone flexibility into MedusaDock by implementing ensemble docking in a sequential manner for a set of distinct receptor backbone conformations. We generate corresponding backbone ensembles to capture backbone changes upon binding to different ligands, as observed experimentally. We develop a simple clustering and ranking approach to select the top poses as blind predictions. We applied our method in the CSAR2011 benchmark exercise. In 28 out of 35 cases (80%) where the ligand-receptor complex structures were released, we were able to predict near-native poses (<2.5 Å RMSD), the highest success rate reported for CSAR2011. This result highlights the importance of modeling receptor backbone flexibility to the accurate docking of ligands to flexible targets. We expect a broad application of our fully flexible docking approach in biological studies as well as in rational drug design. PMID:23237273

  1. Backbone of complex networks of corporations: the flow of control.

    PubMed

    Glattfelder, J B; Battiston, S

    2009-09-01

    We present a methodology to extract the backbone of complex networks based on the weight and direction of links, as well as on nontopological properties of nodes. We show how the methodology can be applied in general to networks in which mass or energy is flowing along the links. In particular, the procedure enables us to address important questions in economics, namely, how control and wealth are structured and concentrated across national markets. We report on the first cross-country investigation of ownership networks, focusing on the stock markets of 48 countries around the world. On the one hand, our analysis confirms results expected on the basis of the literature on corporate control, namely, that in Anglo-Saxon countries control tends to be dispersed among numerous shareholders. On the other hand, it also reveals that in the same countries, control is found to be highly concentrated at the global level, namely, lying in the hands of very few important shareholders. Interestingly, the exact opposite is observed for European countries. These results have previously not been reported as they are not observable without the kind of network analysis developed here. PMID:19905177

  2. Backbone of complex networks of corporations: The flow of control

    NASA Astrophysics Data System (ADS)

    Glattfelder, J. B.; Battiston, S.

    2009-09-01

    We present a methodology to extract the backbone of complex networks based on the weight and direction of links, as well as on nontopological properties of nodes. We show how the methodology can be applied in general to networks in which mass or energy is flowing along the links. In particular, the procedure enables us to address important questions in economics, namely, how control and wealth are structured and concentrated across national markets. We report on the first cross-country investigation of ownership networks, focusing on the stock markets of 48 countries around the world. On the one hand, our analysis confirms results expected on the basis of the literature on corporate control, namely, that in Anglo-Saxon countries control tends to be dispersed among numerous shareholders. On the other hand, it also reveals that in the same countries, control is found to be highly concentrated at the global level, namely, lying in the hands of very few important shareholders. Interestingly, the exact opposite is observed for European countries. These results have previously not been reported as they are not observable without the kind of network analysis developed here.

  3. Comparison of Backbone Modification in Protein β-Sheets by α→γ Residue Replacement and α-Residue Methylation

    PubMed Central

    Lengyel, George A.; Reinert, Zachary E.; Griffith, Brian D.

    2014-01-01

    The mimicry of protein tertiary structure by oligomers with unnatural backbones is a significant contemporary research challenge. Among common elements of secondary structure found in natural proteins, sheets have proven the most difficult to address. Here, we report the systematic comparison of different strategies for peptide backbone modification in β-sheets with the goal of identifying the best method for replacing a multi-stranded sheet in a protein tertiary fold. The most effective sheet modifications examined lead to native-like tertiary folding behavior with thermodynamic fold stability comparable to the prototype protein on which the modified backbones are based. PMID:24909436

  4. Spatial variation of earthquake ground motion for application to soil-structure interaction

    SciTech Connect

    Abrahamson, N. )

    1992-03-01

    The spatial variation of strong ground motion from fifteen earthquakes recorded by the Lotung LSST strong motion array is analyzed. The earthquakes range in magnitude from 3.7 to 7.8 and in source distance from 4 to 80 km. In all a total of 533 station pairs are used with station separations ranging from 60 to 85 meters. The spatial variation of ground motion is divided into two parts: variation in the fourier phase (coherence), and variation in the Fourier amplitude. Empirical functions describing the frequency and separation distance dependence of the coherency and amplitude variation appropriate for use in engineering analyses are derived. Taken together, the spatial variation functions given in this study provide a complete description of the statistical properties of the horizontal components of the seismic wavefield assuming plane wave propagation for the S-wave window. Since the S-waves generally cause the largest shaking, these spatial variation functions are appropriate for use in engineering analyses of large structures.

  5. Spatial variation of earthquake ground motion for application to soil-structure interaction. Final report

    SciTech Connect

    Abrahamson, N.

    1992-03-01

    The spatial variation of strong ground motion from fifteen earthquakes recorded by the Lotung LSST strong motion array is analyzed. The earthquakes range in magnitude from 3.7 to 7.8 and in source distance from 4 to 80 km. In all a total of 533 station pairs are used with station separations ranging from 60 to 85 meters. The spatial variation of ground motion is divided into two parts: variation in the fourier phase (coherence), and variation in the Fourier amplitude. Empirical functions describing the frequency and separation distance dependence of the coherency and amplitude variation appropriate for use in engineering analyses are derived. Taken together, the spatial variation functions given in this study provide a complete description of the statistical properties of the horizontal components of the seismic wavefield assuming plane wave propagation for the S-wave window. Since the S-waves generally cause the largest shaking, these spatial variation functions are appropriate for use in engineering analyses of large structures.

  6. Parametric reduced-order models of battery pack vibration including structural variation and prestress effects

    NASA Astrophysics Data System (ADS)

    Hong, Sung-Kwon; Epureanu, Bogdan I.; Castanier, Matthew P.

    2014-09-01

    The goal of this work is to develop a numerical model for the vibration of hybrid electric vehicle (HEV) battery packs to enable probabilistic forced response simulations for the effects of variations. There are two important types of variations that affect their structural response significantly: the prestress that is applied when joining the cells within a pack; and the small, random structural property discrepancies among the cells of a battery pack. The main contributions of this work are summarized as follows. In order to account for these two important variations, a new parametric reduced order model (PROM) formulation is derived by employing three key observations: (1) the stiffness matrix can be parameterized for different levels of prestress, (2) the mode shapes of a battery pack with cell-to-cell variation can be represented as a linear combination of the mode shapes of the nominal system, and (3) the frame holding each cell has vibratory motion. A numerical example of an academic battery pack with pouch cells is presented to demonstrate that the PROM captures the effects of both prestress and structural variation on battery packs. The PROM is validated numerically by comparing full-order finite element models (FEMs) of the same systems.

  7. Molecular structure of deoxyadenylyl-3'-methylphosphonate-5'-thymidine dihydrate, (d-ApT x 2H2O), a dinucleoside monophosphate with neutral phosphodiester backbone. An X-ray crystal study.

    PubMed Central

    Chacko, K K; Lindner, K; Saenger, W; Miller, P S

    1983-01-01

    dApT, a modified deoxyribose dinucleoside phosphate with an uncharged methylphosphonate group, crystallizes as dihydrate in space group P2(1)2(1)2, a = 9.629(3), b = 20.884(6) and c = 14.173(4)A, Z = 4. The structure has been determined using 2176 X-ray diffractometer reflections and refined to a final R of 0.105. Torsion angles about P-O(5') and P-O(3') bonds are -91.8 degrees and 117.8 degrees. The former is in the normal (-)gauche range while the latter is eclipsed. Bases are oriented anti, the sugar of adenosine is puckered 2T3 (C(2')endo) whereas that of thymidine displays puckering disorder with major and minor occupancy sites. Major site is a half-chair 2T (C(2')endo-C(1')exo) and minor site an envelope 3T2 (C(3(1)endo). Adenine and thymine bases of symmetry related molecules form reversed Hoogsteen type base pairs, water molecules are disordered in the crystal lattice. PMID:6574427

  8. Histidine-Directed Arylation/Alkenylation of Backbone N-H Bonds Mediated by Copper(II).

    PubMed

    Ohata, Jun; Minus, Matthew B; Abernathy, Morgan E; Ball, Zachary T

    2016-06-22

    Chemical modification of proteins and peptides represents a challenge of reaction design as well as an important biological tool. In contrast to side-chain modification, synthetic methods to alter backbone structure are extremely limited. In this communication, copper-mediated backbone N-alkenylation or N-arylation of peptides and proteins by direct modification of natural sequences is described. Histidine residues direct oxidative coupling of boronic acids at the backbone NH of a neighboring amino acid. The mild reaction conditions in common physiological buffers, at ambient temperature, are compatible with proteins and biological systems. This simple reaction demonstrates the potential for directed reactions in complex systems to allow modification of N-H bonds that directly affect polypeptide structure, stability, and function. PMID:27249339

  9. Constraints on field theoretical models for variation of the fine structure constant

    NASA Astrophysics Data System (ADS)

    Steinhardt, Charles L.

    2005-02-01

    Recent theoretical ideas and observational claims suggest that the fine structure constant α may be variable. We examine a spectrum of models in which α is a function of a scalar field. Specifically, we consider three scenarios: oscillating α, monotonic time variation of α, and time-independent α that is spatially varying. We examine the constraints imposed upon these theories by cosmological observations, particle detector experiments, and “fifth force” experiments. These constraints are very strong on models involving oscillation but cannot compete with bounds from the Oklo subnuclear reactor on models with monotonic timelike variation of α. One particular model with spatial variation is consistent with all current experimental and observational measurements, including those from two seemingly conflicting measurements of the fine structure constant using the many multiplet method on absorption lines.

  10. The effect of structural stiffness variations on the onset of cross-flow VIV

    NASA Astrophysics Data System (ADS)

    Lee, Li

    2013-02-01

    This brief communication discusses test results in an earlier publication, which reveal that the onset of vortex-induced vibration (VIV) of a cylindrical structure is greatly influenced by its stiffness variations. An explanation is provided and a dimensionless parameter is proposed as an indicator to the onset of the cross-flow motion. The importance of this finding to VIV design of the cylindrical structures for marine applications is suggested.

  11. The determination of the in situ structure by nuclear spin contrast variation

    SciTech Connect

    Stuhrmann, H.B.; Nierhaus, K.H.

    1994-12-31

    Polarized neutron scattering from polarized nuclear spins in hydrogenous substances opens a new way of contrast variation. The enhanced contrast due to proton spin polarization was used for the in situ structure determination of tRNA of the functional complex of the E.coli ribosome.

  12. A study on the variation with temperature of fixed charge and membrane structure of cellophane membrane

    SciTech Connect

    Benavente, J. )

    1991-02-01

    Membrane potentials for a cellophane membrane at different temperatures (25-60C) have been measured. Experimental results were analyzed on the basis of the Kobatake equation, and some characteristic parameters have been estimated. The activation energy was also obtained. A variation of the membrane structure at the highest temperature studied has been found.

  13. Variation in mangrove forest structure and sediment characteristics in Bocas del Toro, Panama

    USGS Publications Warehouse

    Lovelock, C.E.; Feller, Ilka C.; McKee, K.L.; Thompson, R.

    2005-01-01

    Mangrove forest structure and sediment characteristics were examined in the extensive mangroves of Bocas del Toro, Republic of Panama. Forest structure was characterized to determine if spatial vegetation patterns were repeated over the Bocas del Toro landscape. Using a series of permanent plots and transects we found that the forests of Bocas del Toro were dominated by Rhizophora mangle with very few individuals of Avicennia germinans and Laguncularia racemosa. Despite this low species diversity, there was large variation in forest structure and in edaphic conditions (salinity, concentration of available phosphorus, Eh and sulphide concentration). Aboveground biomass varied 20-fold, from 6.8 Mg ha-1 in dwarf forests to 194.3 Mg ha-1 in the forests fringing the land. But variation in forest structure was predictable across the intertidal zone. There was a strong tree height gradient from seaward fringe (mean tree height 3.9 m), decreasing in stature in the interior dwarf forests (mean tree height 0.7 m), and increasing in stature in forests adjacent to the terrestrial forest (mean tree height 4.1 m). The predictable variation in forest structure emerges due to the complex interactions among edaphic and plant factors. Identifying predictable patterns in forest structure will aid in scaling up the ecosystem services provided by mangrove forests in coastal landscapes. Copyright 2005 College of Arts and Sciences.

  14. Photocentric variability of quasars caused by variations in their inner structure: consequences for Gaia measurements

    NASA Astrophysics Data System (ADS)

    Popović, L. Č.; Jovanović, P.; Stalevski, M.; Anton, S.; Andrei, A. H.; Kovačević, J.; Baes, M.

    2012-02-01

    Context. We study the photocenter position variability caused by variations in the quasar inner structure. We consider the variability in the accretion disk emissivity and torus structure variability caused by the different illumination by the central source. We discuss the possible detection of these effects by Gaia. Observations of the photocenter variability in two AGNs, SDSS J121855+020002 and SDSS J162011+1724327 have been reported and discussed. Aims: For variations in the quasar inner structure, we explore how much this effect can affect the position determination and whether it can (or not) be detected with the Gaia mission. Methods: We use models of (a) a relativistic disk, including the perturbation that can increase the brightness of part of the disk, and consequently offset the photocenter position, and (b) a dusty torus that absorbs and re-emits the incoming radiation from the accretion disk (central continuum source). We estimate the value of the photocenter offset caused by these two effects. Results: We found that perturbations in the inner structure can cause a significant offset to the photocenter. This offset depends on the characteristics of both the perturbation and accretion disk and on the structure of the torus. In the case of the two considered QSOs, the observed photocenter offsets cannot be explained by variations in the accretion disk and other effects should be considered. We discuss the possibility of exploding stars very close to the AGN source, and also that there are two variable sources at the center of these two AGNs that may indicate a binary supermassive black hole system on a kpc (pc) scale. Conclusions: The Gaia mission seems to be very promising, not only for astrometry, but also for exploring the inner structure of AGNs. We conclude that variations in the quasar inner structure can affect the observed photocenter (by up to several mas). There is a chance to observe such an effect in the case of bright and low-redshift QSOs.

  15. Monitoring Backbone Hydrogen-Bond Formation in β-Barrel Membrane Protein Folding.

    PubMed

    Raschle, Thomas; Rios Flores, Perla; Opitz, Christian; Müller, Daniel J; Hiller, Sebastian

    2016-05-10

    β-barrel membrane proteins are key components of the outer membrane of bacteria, mitochondria and chloroplasts. Their three-dimensional structure is defined by a network of backbone hydrogen bonds between adjacent β-strands. Here, we employ hydrogen-deuterium (H/D) exchange in combination with NMR spectroscopy and mass spectrometry to monitor backbone hydrogen bond formation during folding of the outer membrane protein X (OmpX) from E. coli in detergent micelles. Residue-specific kinetics of interstrand hydrogen-bond formation were found to be uniform in the entire β-barrel and synchronized to formation of the tertiary structure. OmpX folding thus propagates via a long-lived conformational ensemble state in which all backbone amide protons exchange with the solvent and engage in hydrogen bonds only transiently. Stable formation of the entire OmpX hydrogen bond network occurs downhill of the rate-limiting transition state and thus appears cooperative on the overall folding time scale. PMID:27062600

  16. Spatial and spatiotemporal variation in metapopulation structure affects population dynamics in a passively dispersing arthropod.

    PubMed

    De Roissart, Annelies; Wang, Shaopeng; Bonte, Dries

    2015-11-01

    The spatial and temporal variation in the availability of suitable habitat within metapopulations determines colonization-extinction events, regulates local population sizes and eventually affects local population and metapopulation stability. Insights into the impact of such a spatiotemporal variation on the local population and metapopulation dynamics are principally derived from classical metapopulation theory and have not been experimentally validated. By manipulating spatial structure in artificial metapopulations of the spider mite Tetranychus urticae, we test to which degree spatial (mainland-island metapopulations) and spatiotemporal variation (classical metapopulations) in habitat availability affects the dynamics of the metapopulations relative to systems where habitat is constantly available in time and space (patchy metapopulations). Our experiment demonstrates that (i) spatial variation in habitat availability decreases variance in metapopulation size and decreases density-dependent dispersal at the metapopulation level, while (ii) spatiotemporal variation in habitat availability increases patch extinction rates, decreases local population and metapopulation sizes and decreases density dependence in population growth rates. We found dispersal to be negatively density dependent and overall low in the spatial variable mainland-island metapopulation. This demographic variation subsequently impacts local and regional population dynamics and determines patterns of metapopulation stability. Both local and metapopulation-level variabilities are minimized in mainland-island metapopulations relative to classical and patchy ones. PMID:25988264

  17. Electron transfer dissociation reveals changes in the cleavage frequencies of backbone bonds distant to amide-to-ester substitutions in polypeptides.

    PubMed

    Hansen, Thomas A; Jung, Hye R; Kjeldsen, Frank

    2011-11-01

    Interrogation of electron transfer dissociation (ETD) mass spectra of peptide amide-to-ester backbone bond substituted analogues (depsipeptides) reveals substantial differences in the entire backbone cleavage frequencies. It is suggested that the point permutation of backbone bonds leads to changes in the predominant ion structures by removal/weakening of specific hydrogen bonding. ETD responds to these changes by redistributing the cleavage frequencies of the peptide backbone bonds. In comparison, no distinction between depsi-/peptide was observed using collision-activated dissociation, which is consistent with a general unfolding and elimination of structural information of these ions. These results should encourage further exploration of depsipeptides for gas-phase structural characterization. PMID:21952783

  18. Environmental diel variation, parasite loads, and local population structuring of a mixed-mating mangrove fish.

    PubMed

    Ellison, Amy; Wright, Patricia; Taylor, D Scott; Cooper, Chris; Regan, Kelly; Currie, Suzie; Consuegra, Sofia

    2012-07-01

    Genetic variation within populations depends on population size, spatial structuring, and environmental variation, but is also influenced by mating system. Mangroves are some of the most productive and threatened ecosystems on earth and harbor a large proportion of species with mixed-mating (self-fertilization and outcrossing). Understanding population structuring in mixed-mating species is critical for conserving and managing these complex ecosystems. Kryptolebias marmoratus is a unique mixed-mating vertebrate inhabiting mangrove swamps under highly variable tidal regimes and environmental conditions. We hypothesized that geographical isolation and ecological pressures influence outcrossing rates and genetic diversity, and ultimately determine the local population structuring of K. marmoratus. By comparing genetic variation at 32 microsatellites, diel fluctuations of environmental parameters, and parasite loads among four locations with different degrees of isolation, we found significant differences in genetic diversity and genotypic composition but little evidence of isolation by distance. Locations also differed in environmental diel fluctuation and parasite composition. Our results suggest that mating system, influenced by environmental instability and parasites, underpins local population structuring of K. marmoratus. More generally, we discuss how the conservation of selfing species inhabiting mangroves and other biodiversity hotspots may benefit from knowledge of mating strategies and population structuring at small spatial scales. PMID:22957172

  19. Brain structure variation in great apes, with attention to the mountain gorilla (Gorilla beringei beringei).

    PubMed

    Sherwood, Chet C; Cranfield, Michael R; Mehlman, Patrick T; Lilly, Alecia A; Garbe, Jo Anne L; Whittier, Christopher A; Nutter, Felicia B; Rein, Thomas R; Bruner, Harlan J; Holloway, Ralph L; Tang, Cheuk Y; Naidich, Thomas P; Delman, Bradley N; Steklis, H Dieter; Erwin, Joseph M; Hof, Patrick R

    2004-07-01

    This report presents data regarding the brain structure of mountain gorillas (Gorilla beringei beringei) in comparison with other great apes. Magnetic resonance (MR) images of three mountain gorilla brains were obtained with a 3T scanner, and the volume of major neuroanatomical structures (neocortical gray matter, hippocampus, thalamus, striatum, and cerebellum) was measured. These data were included with our existing database that includes 23 chimpanzees, three western lowland gorillas, and six orangutans. We defined a multidimensional space by calculating the principal components (PCs) from the correlation matrix of brain structure fractions in the well-represented sample of chimpanzees. We then plotted data from all of the taxa in this space to examine phyletic variation in neural organization. Most of the variance in mountain gorillas, as well as other great apes, was contained within the chimpanzee range along the first two PCs, which accounted for 61.73% of the total variance. Thus, the majority of interspecific variation in brain structure observed among these ape taxa was no greater than the within-species variation seen in chimpanzees. The loadings on PCs indicated that the brain structure of great apes differs among taxa mostly in the relative sizes of the striatum, cerebellum, and hippocampus. These findings suggest possible functional differences among taxa in terms of neural adaptations for ecological and locomotor capacities. Importantly, these results fill a critical gap in current knowledge regarding great ape neuroanatomical diversity. PMID:15258959

  20. No association between schizophrenia susceptibility variants and macroscopic structural brain volume variation in healthy subjects.

    PubMed

    Li, Ming; Huang, Liang; Wang, Jinkai; Su, Bing; Luo, Xiong-Jian

    2016-03-01

    Previous studies have suggested that genetic variants for schizophrenia susceptibility might contribute to structural brain volume variations in schizophrenia patients, including total brain volume, hippocampal volume, and amygdalar volume. However, whether these schizophrenia susceptibility variants are associated with macroscopic structural brain volume (i.e., intracranial volume, total brain volume, and hippocampal volume) in healthy subjects is still unclear. In this study, we investigated the associations between 47 schizophrenia susceptibility variants (from 25 well-characterized schizophrenia susceptibility genes) and cranial volume variation in a healthy Chinese sample (N = 1,013). We also extracted the association between these 47 schizophrenia risk variants and the macroscopic structural brain volume (intracranial volume, total brain volume and hippocampal volume) in a large healthy sample of European ancestry (ENIGMA sample, N = 5,775). We identified several single-nucleotide polymorphisms (SNPs) nominally associated with intracranial volume, total brain volume, and hippocampal volume at P < 0.05 (uncorrected). However, after Bonferroni corrections for multiple testing, no SNP showed significant association. Hence, our results do not support previous observations that schizophrenia susceptibility variants are associated with brain structure (e.g., hippocampal volume) in healthy individuals, and indicate that single schizophrenia risk variant may not contribute significantly to macroscopic brain structure (e.g., intracranial volume or hippocampal volume) variation in healthy subjects. PMID:26437209

  1. Variation in the structural changes of myoglobin in the presence of several protic ionic liquid.

    PubMed

    Attri, Pankaj; Jha, Indrani; Choi, Eun Ha; Venkatesu, Pannuru

    2014-08-01

    Protein stability in ionic solution depends on the delicate balance between protein-ion and ion-ion interactions. To address the ion specific effects on the protein, we have examined the stability of myoglobin (Mb) in the presence of buffer and ammonium-based ionic liquids (ILs) (50%, v/v). Here, fluorescence and circular dichroism (CD) spectroscopy experiments are used to study the influence of ILs on structure and stability of Mb. Our experimental results reveal that more viscous ILs (sulphate or phosphate ions) are stabilizers and therefore more biocompatible for Mb structure. Surprisingly, the less viscous ILs such as acetate anion based ILs are destabilizers for the native structure of Mb. Our results explicitly elucidate that anion variation has significant influence on Mb stability efficiency than cation variation. This study provides insight into anion effects on protein stability and explains that the intrasolvent interactions can be leveraged to enhance the stability. PMID:24857872

  2. Intraspecific phytochemical variation shapes community and population structure for specialist caterpillars.

    PubMed

    Glassmire, Andrea E; Jeffrey, Christopher S; Forister, Matthew L; Parchman, Thomas L; Nice, Chris C; Jahner, Joshua P; Wilson, Joseph S; Walla, Thomas R; Richards, Lora A; Smilanich, Angela M; Leonard, Michael D; Morrison, Colin R; Simbaña, Wilmer; Salagaje, Luis A; Dodson, Craig D; Miller, Jim S; Tepe, Eric J; Villamarin-Cortez, Santiago; Dyer, Lee A

    2016-10-01

    Chemically mediated plant-herbivore interactions contribute to the diversity of terrestrial communities and the diversification of plants and insects. While our understanding of the processes affecting community structure and evolutionary diversification has grown, few studies have investigated how trait variation shapes genetic and species diversity simultaneously in a tropical ecosystem. We investigated secondary metabolite variation among subpopulations of a single plant species, Piper kelleyi (Piperaceae), using high-performance liquid chromatography (HPLC), to understand associations between plant phytochemistry and host-specialized caterpillars in the genus Eois (Geometridae: Larentiinae) and associated parasitoid wasps and flies. In addition, we used a genotyping-by-sequencing approach to examine the genetic structure of one abundant caterpillar species, Eois encina, in relation to host phytochemical variation. We found substantive concentration differences among three major secondary metabolites, and these differences in chemistry predicted caterpillar and parasitoid community structure among host plant populations. Furthermore, E. encina populations located at high elevations were genetically different from other populations. They fed on plants containing high concentrations of prenylated benzoic acid. Thus, phytochemistry potentially shapes caterpillar and wasp community composition and geographic variation in species interactions, both of which can contribute to diversification of plants and insects. PMID:27279551

  3. Sensitivity of hyperfine structure to nuclear radius and quark mass variation

    SciTech Connect

    Dinh, T. H.; Dunning, A.; Dzuba, V. A.; Flambaum, V. V.

    2009-05-15

    To search for the temporal variation in the fundamental constants, one needs to know dependence of atomic transition frequencies on these constants. We study the dependence of the hyperfine structure of atomic s levels on nuclear radius and, via radius, on quark masses. An analytical formula has been derived and tested by the numerical relativistic Hartree-Fock calculations for Rb, Cd{sup +}, Cs, Yb{sup +}, and Hg{sup +}. The results of this work allow the use of the results of past and future atomic clock experiments and quasar spectra measurements to put constraints on time variation in the quark masses.

  4. Vertical structure and variation of currents observed in autumn in the Korea Strait

    NASA Astrophysics Data System (ADS)

    Lee, Sang-Ho; Choi, Byoung-Ju

    2015-06-01

    To observe vertical structure and temporal variations of currents in the Tsushima Warm Current region of the Korea Strait, a moored buoy system was deployed in autumn 2009. The moored buoy system measured vertical profiles of current, temperature, and salinity for 24 days and a background hydrographic survey was performed. Along-strait northeastward currents were dominant in the upper layer (8-35 m). The mean current veers counterclockwise from 48 m to 74 m as much as 50°, and its speed is reduced with depth. There were distinct northward onshore currents near the bottom (65-80 m). It was demonstrated that thermal wind relation holds in the inclined pycnocline layer, which generates the counterclockwise veering current structure. Density gradient along the strait is a main factor producing the cross-strait onshore current component below the upper-layer and the cross-strait density gradient reduces the along-strait current component with depth. Previous studies have never focused on the effect of the along-strait density structure on current structure. The first Empirical Orthogonal Function mode (CM1) of current variability explains 70% of local current variations and its vertical structure is close to the mean current structure. The correlation analysis among variations of CM1 current, slope of sea level anomaly (SSLA) and local wind anomaly revealed that the variation of CM1 current is mainly related to the variation of SSLA across the strait (c-SSLA), which is known to be controlled by remote and local wind forcing. Similarity between vertical structures of mean and CM1 current suggests that thermal wind relation is the main dynamics maintaining the counterclockwise turning of CM1 current below the upper layer although the upperlayer CM1 current is controlled by c-SSLA through barotropic geostrophic relation. Time series of temperature and salinity indicate that the thermohaline front between Korean Coastal Water and Tsushima Warm Current Water meanders in

  5. Constraints on a possible variation of the fine structure constant from galaxy cluster data

    NASA Astrophysics Data System (ADS)

    Holanda, R. F. L.; Landau, S. J.; Alcaniz, J. S.; Sánchez G., I. E.; Busti, V. C.

    2016-05-01

    We propose a new method to probe a possible time evolution of the fine structure constant α from X-ray and Sunyaev-Zel'dovich measurements of the gas mass fraction (fgas) in galaxy clusters. Taking into account a direct relation between variations of α and violations of the distance-duality relation, we discuss constraints on α for a class of dilaton runaway models. Although not yet competitive with bounds from high-z quasar absorption systems, our constraints, considering a sample of 29 measurements of fgas, in the redshift interval 0.14 < z < 0.89, provide an independent estimate of α variation at low and intermediate redshifts. Furthermore, current and planned surveys will provide a larger amount of data and thus allow to improve the limits on α variation obtained in the present analysis.

  6. Spatial structure of 60- and 30-year variations of the geomagnetic field according to data of analytical models

    NASA Astrophysics Data System (ADS)

    Kalugin, V. I.; Rotanova, N. M.; Golovkov, V. P.

    1984-10-01

    The distribution of the amplitudes and phases of 60-year variations of the geomagnetic field on the earth's surface is obtained on the basis of analytical models. It is shown that the characteristic features or foci of these variations have different configurations and a dissimilar intensity. A global map of the spatial distribution of 30-year variations is also obtained; and a comparison of maps of the 60- and 30-year variations shows that, although the structure of the latter variations is more complex, the characteristic foci of both types of variations are manifested in the same regions.

  7. Genetic and Ontogenetic Variation in an Endangered Tree Structures Dependent Arthropod and Fungal Communities

    PubMed Central

    Gosney, Benjamin J.; O′Reilly-Wapstra, Julianne M.; Forster, Lynne G.; Barbour, Robert C.; Iason, Glenn R.; Potts, Brad M.

    2014-01-01

    Plant genetic and ontogenetic variation can significantly impact dependent fungal and arthropod communities. However, little is known of the relative importance of these extended genetic and ontogenetic effects within a species. Using a common garden trial, we compared the dependent arthropod and fungal community on 222 progeny from two highly differentiated populations of the endangered heteroblastic tree species, Eucalyptus morrisbyi. We assessed arthropod and fungal communities on both juvenile and adult foliage. The community variation was related to previous levels of marsupial browsing, as well as the variation in the physicochemical properties of leaves using near-infrared spectroscopy. We found highly significant differences in community composition, abundance and diversity parameters between eucalypt source populations in the common garden, and these were comparable to differences between the distinctive juvenile and adult foliage. The physicochemical properties assessed accounted for a significant percentage of the community variation but did not explain fully the community differences between populations and foliage types. Similarly, while differences in population susceptibility to a major marsupial herbivore may result in diffuse genetic effects on the dependent community, this still did not account for the large genetic-based differences in dependent communities between populations. Our results emphasize the importance of maintaining the populations of this rare species as separate management units, as not only are the populations highly genetically structured, this variation may alter the trajectory of biotic colonization of conservation plantings. PMID:25469641

  8. Genetic and ontogenetic variation in an endangered tree structures dependent arthropod and fungal communities.

    PubMed

    Gosney, Benjamin J; O Reilly-Wapstra, Julianne M; Forster, Lynne G; Barbour, Robert C; Iason, Glenn R; Potts, Brad M

    2014-01-01

    Plant genetic and ontogenetic variation can significantly impact dependent fungal and arthropod communities. However, little is known of the relative importance of these extended genetic and ontogenetic effects within a species. Using a common garden trial, we compared the dependent arthropod and fungal community on 222 progeny from two highly differentiated populations of the endangered heteroblastic tree species, Eucalyptus morrisbyi. We assessed arthropod and fungal communities on both juvenile and adult foliage. The community variation was related to previous levels of marsupial browsing, as well as the variation in the physicochemical properties of leaves using near-infrared spectroscopy. We found highly significant differences in community composition, abundance and diversity parameters between eucalypt source populations in the common garden, and these were comparable to differences between the distinctive juvenile and adult foliage. The physicochemical properties assessed accounted for a significant percentage of the community variation but did not explain fully the community differences between populations and foliage types. Similarly, while differences in population susceptibility to a major marsupial herbivore may result in diffuse genetic effects on the dependent community, this still did not account for the large genetic-based differences in dependent communities between populations. Our results emphasize the importance of maintaining the populations of this rare species as separate management units, as not only are the populations highly genetically structured, this variation may alter the trajectory of biotic colonization of conservation plantings. PMID:25469641

  9. Inter-chromosomal variation in the pattern of human population genetic structure.

    PubMed

    Baye, Tesfaye M

    2011-05-01

    Emerging technologies now make it possible to genotype hundreds of thousands of genetic variations in individuals, across the genome. The study of loci at finer scales will facilitate the understanding of genetic variation at genomic and geographic levels. We examined global and chromosomal variations across HapMap populations using 3.7 million single nucleotide polymorphisms to search for the most stratified genomic regions of human populations and linked these regions to ontological annotation and functional network analysis. To achieve this, we used five complementary statistical and genetic network procedures: principal component (PC), cluster, discriminant, fixation index (FST) and network/pathway analyses. At the global level, the first two PC scores were sufficient to account for major population structure; however, chromosomal level analysis detected subtle forms of population structure within continental populations, and as many as 31 PCs were required to classify individuals into homogeneous groups. Using recommended population ancestry differentiation measures, a total of 126 regions of the genome were catalogued. Gene ontology and networks analyses revealed that these regions included the genes encoding oculocutaneous albinism II (OCA2), hect domain and RLD 2 (HERC2), ectodysplasin A receptor (EDAR) and solute carrier family 45, member 2 (SLC45A2). These genes are associated with melanin production, which is involved in the development of skin and hair colour, skin cancer and eye pigmentation. We also identified the genes encoding interferon-γ (IFNG) and death-associated protein kinase 1 (DAPK1), which are associated with cell death, inflammatory and immunological diseases. An in-depth understanding of these genomic regions may help to explain variations in adaptation to different environments. Our approach offers a comprehensive strategy for analysing chromosome-based population structure and differentiation, and demonstrates the application of

  10. Backbone and sidechain 1H, 15N and 13C assignments of the KSR1 CA1 domain

    PubMed Central

    Koveal, Dorothy; Pinheiro, Anderson S.; Peti, Wolfgang; Page, Rebecca

    2014-01-01

    The backbone and side chain resonance assignments of the murine KSR1 CA1 domain have been determined based on triple-resonance experiments using uniformly [13C, 15N]-labeled protein. This assignment is the first step towards the determination of the three-dimensional structure of the unique KSR1 CA1 domain. PMID:20737253

  11. The Graphical Representation of the Digital Astronaut Physiology Backbone

    NASA Technical Reports Server (NTRS)

    Briers, Demarcus

    2010-01-01

    This report summarizes my internship project with the NASA Digital Astronaut Project to analyze the Digital Astronaut (DA) physiology backbone model. The Digital Astronaut Project (DAP) applies integrated physiology models to support space biomedical operations, and to assist NASA researchers in closing knowledge gaps related to human physiologic responses to space flight. The DA physiology backbone is a set of integrated physiological equations and functions that model the interacting systems of the human body. The current release of the model is HumMod (Human Model) version 1.5 and was developed over forty years at the University of Mississippi Medical Center (UMMC). The physiology equations and functions are scripted in an XML schema specifically designed for physiology modeling by Dr. Thomas G. Coleman at UMMC. Currently it is difficult to examine the physiology backbone without being knowledgeable of the XML schema. While investigating and documenting the tags and algorithms used in the XML schema, I proposed a standard methodology for a graphical representation. This standard methodology may be used to transcribe graphical representations from the DA physiology backbone. In turn, the graphical representations can allow examination of the physiological functions and equations without the need to be familiar with the computer programming languages or markup languages used by DA modeling software.

  12. Determination of backbone chain direction of PDA using FFM

    NASA Astrophysics Data System (ADS)

    Jo, Sadaharu; Okamoto, Kentaro; Takenaga, Mitsuru

    2010-01-01

    The effect of backbone chains on friction force was investigated on both Langmuir-Blodgett (LB) films of 10,12-heptacosadiynoic acid and the (0 1 0) surfaces of single crystals of 2,4-hexadiene-1,6-diol using friction force microscopy (FFM). It was observed that friction force decreased when the scanning direction was parallel to the [0 0 1] direction in both samples. Moreover, friction force decreased when the scanning direction was parallel to the crystallographic [1 0 2], [1 0 1], [1 0 0] and [1 0 1¯] directions in only the single crystals. For the LB films, the [0 0 1] direction corresponds to the backbone chain direction of 10,12-heptacosadiynoic acid. For the single crystals, both the [0 0 1] and [1 0 1] directions correspond to the backbone chain direction, and the [1 0 2], [1 0 0] and [1 0 1¯] directions correspond to the low-index crystallographic direction. In both the LB films and single crystals, the friction force was minimized when the directions of scanning and the backbone chain were parallel.

  13. Increasing protein production by directed vector backbone evolution

    PubMed Central

    2013-01-01

    Recombinant protein production in prokaryotic and eukaryotic organisms was a key enabling technology for the rapid development of industrial and molecular biotechnology. However, despite all progress the improvement of protein production is an ongoing challenge and of high importance for cost-effective enzyme production. With the epMEGAWHOP mutagenesis protocol for vector backbone optimization we report a novel directed evolution based approach to increase protein production levels by randomly introducing mutations in the vector backbone. In the current study we validate the epMEGAWHOP mutagenesis protocol for three different expression systems. The latter demonstrated the general applicability of the epMEGAWHOP method. Cellulase and lipase production was doubled in one round of directed evolution by random mutagenesis of pET28a(+) and pET22b(+) vector backbones. Protease production using the vector pHY300PLK was increased ~4-times with an average of ~1.25 mutations per kb vector backbone. The epMEGAWHOP does not require any rational understanding of the expression machinery and can generally be applied to enzymes, expression vectors and related hosts. epMEGAWHOP is therefore from our point of view a robust, rapid and straight forward alternative for increasing protein production in general and for biotechnological applications. PMID:23890095

  14. Protein-Backbone Thermodynamics across the Membrane Interface.

    PubMed

    Bereau, Tristan; Kremer, Kurt

    2016-07-01

    The thermodynamics of insertion of a protein in a membrane depends on the fine interplay between backbone and side-chain contributions interacting with the lipid environment. Using computer simulations, we probe how different descriptions of the backbone glycyl unit affect the thermodynamics of insertion of individual residues, dipeptides, and entire transmembrane helices. Due to the lack of reference data, we first introduce an efficient methodology to estimate atomistic potential of mean force (PMF) curves from a series of representative and uncorrelated coarse-grained (CG) snapshots. We find strong discrepancies between two CG models, Martini and PLUM, against reference atomistic PMFs and experiments. Atomistic simulations suggest a weak free energy of insertion between water and a POPC membrane for the glycyl unit, in overall agreement with experimental results despite severe assumptions in our calculations. We show that refining the backbone contribution in PLUM significantly improves the PMF of insertion of the WALP16 transmembrane peptide. An improper balance between the glycyl backbone and the attached side chain will lead to energetic artifacts, rationalizing Martini's overstabilization of WALP's adsorbed interfacial state. It illustrates difficulties associated with free-energy-based parametrizations of single-residue models, as the relevant free energy of partitioning used for force-field parametrization does not arise from the entire residue but rather the solvent-accessible chemical groups. PMID:27138459

  15. Backbone additivity in the transfer model of protein solvation

    PubMed Central

    Hu, Char Y; Kokubo, Hironori; Lynch, Gillian C; Bolen, D Wayne; Pettitt, B Montgomery

    2010-01-01

    The transfer model implying additivity of the peptide backbone free energy of transfer is computationally tested. Molecular dynamics simulations are used to determine the extent of change in transfer free energy (ΔGtr) with increase in chain length of oligoglycine with capped end groups. Solvation free energies of oligoglycine models of varying lengths in pure water and in the osmolyte solutions, 2M urea and 2M trimethylamine N-oxide (TMAO), were calculated from simulations of all atom models, and ΔGtr values for peptide backbone transfer from water to the osmolyte solutions were determined. The results show that the transfer free energies change linearly with increasing chain length, demonstrating the principle of additivity, and provide values in reasonable agreement with experiment. The peptide backbone transfer free energy contributions arise from van der Waals interactions in the case of transfer to urea, but from electrostatics on transfer to TMAO solution. The simulations used here allow for the calculation of the solvation and transfer free energy of longer oligoglycine models to be evaluated than is currently possible through experiment. The peptide backbone unit computed transfer free energy of −54 cal/mol/M compares quite favorably with −43 cal/mol/M determined experimentally. PMID:20306490

  16. Cooperative UAV-Based Communications Backbone for Sensor Networks

    SciTech Connect

    Roberts, R S

    2001-10-07

    The objective of this project is to investigate the use of unmanned air vehicles (UAVs) as mobile, adaptive communications backbones for ground-based sensor networks. In this type of network, the UAVs provide communication connectivity to sensors that cannot communicate with each other because of terrain, distance, or other geographical constraints. In these situations, UAVs provide a vertical communication path for the sensors, thereby mitigating geographic obstacles often imposed on networks. With the proper use of UAVs, connectivity to a widely disbursed sensor network in rugged terrain is readily achieved. Our investigation has focused on networks where multiple cooperating UAVs are used to form a network backbone. The advantage of using multiple UAVs to form the network backbone is parallelization of sensor connectivity. Many widely spaced or isolated sensors can be connected to the network at once using this approach. In these networks, the UAVs logically partition the sensor network into sub-networks (subnets), with one UAV assigned per subnet. Partitioning the network into subnets allows the UAVs to service sensors in parallel thereby decreasing the sensor-to-network connectivity. A UAV services sensors in its subnet by flying a route (path) through the subnet, uplinking data collected by the sensors, and forwarding the data to a ground station. An additional advantage of using multiple UAVs in the network is that they provide redundancy in the communications backbone, so that the failure of a single UAV does not necessarily imply the loss of the network.

  17. Backbone Additivity in the Transfer Model of Protein Solvation

    SciTech Connect

    Hu, Char Y.; Kokubo, Hironori; Lynch, Gillian C.; Bolen, D Wayne; Pettitt, Bernard M.

    2010-05-01

    The transfer model implying additivity of the peptide backbone free energy of transfer is computationally tested. Molecular dynamics simulations are used to determine the extent of change in transfer free energy (ΔGtr) with increase in chain length of oligoglycine with capped end groups. Solvation free energies of oligoglycine models of varying lengths in pure water and in the osmolyte solutions, 2M urea and 2M trimethylamine N-oxide (TMAO), were calculated from simulations of all atom models, and ΔGtr values for peptide backbone transfer from water to the osmolyte solutions were determined. The results show that the transfer free energies change linearly with increasing chain length, demonstrating the principle of additivity, and provide values in reasonable agreement with experiment. The peptide backbone transfer free energy contributions arise from van der Waals interactions in the case of transfer to urea, but from electrostatics on transfer to TMAO solution. The simulations used here allow for the calculation of the solvation and transfer free energy of longer oligoglycine models to be evaluated than is currently possible through experiment. The peptide backbone unit computed transfer free energy of –54 cal/mol/Mcompares quite favorably with –43 cal/mol/M determined experimentally.

  18. Building an Archive Backbone Extending TAP

    NASA Astrophysics Data System (ADS)

    Molinaro, M.; Apollo, P.; Knapic, C.; Smareglia, R.

    2014-05-01

    A data center (DC) willing to add VO (Virtual Observatory) capabilities to existing archival resources, or new ones, will probably face some issues regarding the constraints on the existing structure of the datasets. On the opposite direction a DC may want to give priority to VO flavored data access but maintain flexibility on proprietary or dedicated access solutions. This contribution tries to delineate a solution, feasible for both approaches, taking advantage of the IVOA (International Virtual Observatory Alliance) existing standards and, at the same time, forcing no constraint at archive generation or ingestion level. The IVOA TAP (Table Access Protocol) specification generalizes the way a set of database schemas and tables, related or not, can be deployed as a queryable resource in the framewok of the Virtual Observatory. The TAP protocol itself has, at its core, a DB schema, named TAP_SCHEMA, that actually acts as an attribute-extended information schema for the exposed set of tables; the TAP_SCHEMA, in short, describes the content of the schemas and tables, and their connections, in a VO aware flavour. It seems then quite immediate to think about pushing the generalization step a little further, i.e. to extend the TAP_SCHEMA itself to provide a more general description of an astrophysical archive (or part of it). Here we discuss on how, adding optional tables and columns to the TAP_SCHEMA, it would be possible to create an archive thin layer solution in terms of this DB schema alongside with a content manager application for it. The goal is to provide a re-usable, configurable connection between an archive's back end and front end, having the benefit of creating a VO translation layer to ease VO resource and service deployment and preserving custom data access and publishing.

  19. Long-term flux density variations of pulsars: Theoretical structure functions and comparisons with observations

    NASA Astrophysics Data System (ADS)

    Zhou, A. Z.; Wu, X. J.; Esamdin, A.

    2003-06-01

    By means of the refractive interstellar scintillation theory (RISS), the flux density structure functions of PSRs B1642-03, B0736-40, B0740-28 and B0329+54 are calculated and compared with the observations at 610 MHz by Stinebring et al. (\\cite{Stinebring00}, hereafter S2000). The theoretical results are in good agreement with observations and the spectra of the electron density fluctuation are all consistent with the Kolmogorov spectra. The theoretical modulation indices m are comparatively less sensitive to the distance H from the observer to the scattering screen but critically depend on the scattering strength line CN2. The structure function does not change remarkably with the variation of H if the scattering screen is closer to the pulsar than to the observer. The results in this paper indicate that the flux density variations observed for these four pulsars are due to a propagation effect (refractive scintillation), not to the intrinsic variability.

  20. Ultrafast band-structure variations induced by fast Au ions in BeO

    NASA Astrophysics Data System (ADS)

    Schiwietz, G.; Czerski, K.; Grande, P. L.; Koteski, V.; Staufenbiel, F.

    2011-05-01

    Auger-electron spectra associated with Be atoms in the pure metal lattice and in an oxide have been investigated for 1.8 MeV/u 129Au 41+ ions and 2.7 keV primary electrons. The excitation and local energy transfer by such fast primary particles in solids is dominated by electronic processes. The electron-induced spectrum is compared to calculated band-structure results and it is relatively well understood. For the heavy-ion case, however, we observe a significant variation of the Auger electron spectrum, related to a variation of the electronic band structure. This spectrum points to a formation of a metal-like meta-stable electronic density of states.

  1. Probing structural variation and multifunctionality in niobium doped bismuth vanadate materials.

    PubMed

    Saithathul Fathimah, Sameera; Prabhakar Rao, Padala; James, Vineetha; Raj, Athira K V; Chitradevi, G R; Leela, Sandhyakumari

    2014-11-14

    Multifunctional materials are developed in BiV1-xNbxO4 solid solutions via structural variations. A citrate gel route has been employed to synthesize these materials followed by calcination at various temperatures leading to fine particles. The effects of niobium doping over the structural variation and its influence on the optical properties are assessed by powder X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and UV-Vis-NIR spectroscopy. These solid solutions exhibit superior coloristic properties which are comparable to commercially available yellow pigments. These materials also show remarkable reflectance in the NIR region which makes them potential candidates for cool roof applications. A notable methylene blue dye degradation property is observed in Nb(5+) doped BiVO4 under sunlight irradiation. PMID:25223954

  2. 21-cm radiation: a new probe of variation in the fine-structure constant.

    PubMed

    Khatri, Rishi; Wandelt, Benjamin D

    2007-03-16

    We investigate the effect of variation in the value of the fine-structure constant (alpha) at high redshifts (recombination > z > 30) on the absorption of the cosmic microwave background (CMB) at 21 cm hyperfine transition of the neutral atomic hydrogen. We find that the 21 cm signal is very sensitive to the variations in alpha and it is so far the only probe of the fine-structure constant in this redshift range. A change in the value of alpha by 1% changes the mean brightness temperature decrement of the CMB due to 21 cm absorption by >5% over the redshift range z < 50. There is an effect of similar magnitude on the amplitude of the fluctuations in the brightness temperature. The redshift of maximum absorption also changes by approximately 5%. PMID:17501040

  3. Enhanced effect of temporal variation of the fine-structure constant in diatomic molecules

    SciTech Connect

    Flambaum, V. V.

    2006-03-15

    We show that the relative effect of variation of the fine-structure constant in microwave transitions between very close and narrow rotational-hyperfine levels may be enhanced 2-3 orders of magnitude in diatomic molecules with unpaired electrons like LaS, LaO, LuS, LuO, YbF, and similar molecular ions. The enhancement is result of cancellation between the hyperfine and rotational intervals.

  4. Fastbreak: a tool for analysis and visualization of structural variations in genomic data

    PubMed Central

    2012-01-01

    Genomic studies are now being undertaken on thousands of samples requiring new computational tools that can rapidly analyze data to identify clinically important features. Inferring structural variations in cancer genomes from mate-paired reads is a combinatorially difficult problem. We introduce Fastbreak, a fast and scalable toolkit that enables the analysis and visualization of large amounts of data from projects such as The Cancer Genome Atlas. PMID:23046488

  5. Variation and Genetic Structure in Platanus mexicana (Platanaceae) along Riparian Altitudinal Gradient

    PubMed Central

    Galván-Hernández, Dulce M.; Lozada-García, J. Armando; Flores-Estévez, Norma; Galindo-González, Jorge; Vázquez-Torres, S. Mario

    2015-01-01

    Platanus mexicana is a dominant arboreal species of riparian ecosystems. These ecosystems are associated with altitudinal gradients that can generate genetic differences in the species, especially in the extremes of the distribution. However, studies on the altitudinal effect on genetic variation to riparian species are scarce. In Mexico, the population of P. mexicana along the Colipa River (Veracruz State) grows below its reported minimum altitude range, possibly the lowest where this tree grows. This suggests that altitude might be an important factor in population genetics differentiation. We examined the genetic variation and population structuring at four sites with different altitudes (70, 200, 600 and 1700 m a.s.l.) using ten inter-simple sequence repeats (ISSR) markers. The highest value for Shannon index and Nei’s gene diversity was obtained at 1700 m a.s.l. (He = 0.27, Ne = 1.47, I = 0.42) and polymorphism reached the top value at the middle altitude (% p = 88.57). Analysis of molecular variance (AMOVA) and STRUCTURE analysis indicated intrapopulation genetic differentiation. The arithmetic average (UPGMA) dendrogram identified 70 m a.s.l. as the most genetically distant site. The genetic structuring resulted from limited gene flow and genetic drift. This is the first report of genetic variation in populations of P. mexicana in Mexico. This research highlights its importance as a dominant species, and its ecological and evolutionary implications in altitudinal gradients of riparian ecosystems. PMID:25607732

  6. Atomic calculations and search for variation of the fine-structure constant in quasar absorption spectra

    NASA Astrophysics Data System (ADS)

    Dzuba, V. A.; Flambaum, V. V.

    A brief review of the search for variation of the fine structure constant in quasar absorption spectra is presented. Special consideration is given to the role of atomic calculations in the analysis of the observed data. A range of methods which allow to perform calculations for atoms or ions with different electron structure and which cover practically all periodic table of elements is discussed. Critical compilation of the results of the calculations as well as a review of the most recent results of the analysis are presented.

  7. Backbone Model of an Aquareovirus Virion by Cryo-Electron Microscopy and Bioinformatics

    PubMed Central

    Cheng, Lingpeng; Zhu, Jiang; Hui, Wong Hoi; Zhang, Xiaokang; Honig, Barry; Fang, Qin; Zhou, Z. Hong

    2010-01-01

    Grass carp reovirus (GCRV) is a member of the aquareovirus genus in the Reoviridae family and has a capsid with two shells—a transcription-competent core surrounded by a coat. We report a near-atomic-resolution reconstruction of the GCRV virion by cryo-electron microscopy and single-particle reconstruction. A backbone model of the GCRV virion, including seven conformers of the five capsid proteins making up the 1500 molecules in both the core and the coat, was derived using cryo-electron microscopy density-map-constrained homology modeling and refinement. Our structure clearly showed that the amino-terminal segment of core protein VP3B forms an ~120-Å-long α-helix-rich extension bridging across the icosahedral 2-fold-symmetry-related molecular interface. The presence of this unique structure across this interface and the lack of an external cementing molecule at this location in GCRV suggest a stabilizing role of this extended amino-terminal density. Moreover, part of this amino-terminal extension becomes invisible in the reconstruction of transcription-competent core particles, suggesting its involvement in endogenous viral RNA transcription. Our structure of the VP1 turret represents its open state, and comparison with its related structures at the closed state suggests hinge-like domain movements associated with the mRNA-capping machinery. Overall, this first backbone model of an aquareovirus virion provides a wealth of structural information for understanding the structural basis of GCRV assembly and transcription. PMID:20036256

  8. Ultraviolet Spectroscopy of Protein Backbone Transitions in Aqueous Solution: combined QM and MM Simulations

    PubMed Central

    Jiang, Jun; Abramavicius, Darius; Bulheller, Benjamin M.; Hirst, Jonathan D.; Mukamel, Shaul

    2010-01-01

    A generalized approach combining Quantum Mechanics (QM) and Molecular Mechanics (MM) calculations is developed to simulate the n → π* and π → π* backbone transitions of proteins in aqueous solution. These transitions, which occur in the ultraviolet (UV) at 180–220 nm, provide a sensitive probe for secondary structures. The excitation Hamiltonian is constructed using high level electronic structure calculations of N-methylacetamide (NMA). Its electrostatic fluctuations are modeled using a new algorithm, EHEF, which combines a molecular dynamics (MD) trajectory obtained with a molecular mechanics forcefield, and electronic structures of sampled MD snapshots calculated by QM. The lineshapes and excitation split-tings induced by the electrostatic environment in the experimental UV linear absorption (LA) and circular dichroism (CD) spectra of several proteins in aqueous solution are reproduced by our calculations. The distinct CD features of α-helix and β-sheet protein structures are observed in the simulations and can be assigned to different backbone geometries. The fine structure of the UV spectra is accurately characterized and enables us to identify signatures of secondary structures. PMID:20503991

  9. Phenotypic variation and water selection potential in the stem structure of invasive alligator weed

    NASA Astrophysics Data System (ADS)

    Du, Leshan; Yang, Beifen; Guan, Wenbin; Li, Junmin

    2016-02-01

    The morphological and anatomical characteristics of stems have been found to be related to drought resistance in plants. Testing the phenotypic selection of water availability on stem anatomical traits would be useful for exploring the evolutionary potential of the stem in response to water availability. To test the phenotypic variation of the stem anatomical traits of an invasive plant in response to water availability, we collected a total of 320 individuals of Alternanthera philoxeroides from 16 populations from terrestrial and aquatic habitats in 8 plots in China and then analyzed the variation, differentiation, plasticity and selection potential of water availability on the stem anatomical traits. We found that except for the thickness of the cortex, all of the examined phenotypic parameters of the A. philoxeroides stem were significantly and positively correlated with soil water availability. The phenotypic differentiation coefficient for all of the anatomical structural parameters indicated that most of the variation existed between habitats within the same plot, whereas there was little variation among plots or among individuals within the same habitat except for variation in the thickness of the cortex. A significant phenotypic plasticity response to water availability was found for all of the anatomical traits of A. philoxeroides stem except for the thickness of the cortex. The associations between fitness and some of the anatomical traits, such as the stem diameter, the cortex area-to-stem area ratio, the pith cavity area-to-stem area ratio and the density of vascular bundles, differed with heterogeneous water availability. In both the aquatic and terrestrial habitats, no significant directional selection gradient was found for the stem diameter, the cortex area-to-stem area ratio or the density of vascular bundles. These results indicated that the anatomical structure of the A. philoxeroides stem may play an important role in the adaptation to changes

  10. [Spatial variation of non-structural carbohydrates in Betula platyphylla and Tilia amurensis stems].

    PubMed

    Zhang, Hai-Yan; Wang, Chuan-Kuan; Wang, Xing-Chang; Cheng, Fang-Yan

    2013-11-01

    Taking the two diffuse-porous tree species Betula platyphylla and Tilia amurensis in a temperate forest in Northeast China as test objects, this paper studied the spatial variation of the non-structural carbohydrates (NSC) concentrations in the stem xylem after leaf-fall. For the two tree species, the concentrations of total non-structural carbohydrate (TNC, soluble sugars plus starch) and soluble sugars in the stem xylem decreased gradually with the increasing depth from cambium to pith, whereas the starch concentration showed little radial variation. There was still a substantial amount of NSC in the inner wood close to pith. The concentrations of the NSC in the two species stems decreased gradually from the stump to the breast height, and then increased vertically. The maximum concentrations of the TNC, soluble sugars, and starch occurred at different heights, depending on the species and the TNC components. The ratio of sugar to starch showed a contrasting vertical trend for the two species, i. e., increasing from the stump to the top for B. platyphylla, but decreasing for T. amurensis. The estimation error of the stem NSC storage was mainly from the axial variation, and then, from the radial variation of NSC concentration. The TNC concentration (1.0% dry mass) in the stem of shade-intolerant species B. platyphylla was significantly lower than that (4.3% dry mass) of shade-tolerant species T. amurensis, which could be related to their different life-history strategies. Applying the sampling protocols considering the axial and radial variations of NSC could effectively reduce the potential uncertainty in estimating the NSC storage at tree or stand level. PMID:24564131

  11. Hydrophobic Core Variations Provide a Structural Framework for Tyrosine Kinase Evolution and Functional Specialization

    PubMed Central

    Kwon, Annie; Byrne, Dominic P.; Ferries, Samantha; Ruan, Zheng; Hanold, Laura E.; Katiyar, Samiksha; Kennedy, Eileen J.; Eyers, Patrick A.; Kannan, Natarajan

    2016-01-01

    Protein tyrosine kinases (PTKs) are a group of closely related enzymes that have evolutionarily diverged from serine/threonine kinases (STKs) to regulate pathways associated with multi-cellularity. Evolutionary divergence of PTKs from STKs has occurred through accumulation of mutations in the active site as well as in the commonly conserved hydrophobic core. While the functional significance of active site variations is well understood, relatively little is known about how hydrophobic core variations contribute to PTK evolutionary divergence. Here, using a combination of statistical sequence comparisons, molecular dynamics simulations, mutational analysis and in vitro thermostability and kinase assays, we investigate the structural and functional significance of key PTK-specific variations in the kinase core. We find that the nature of residues and interactions in the hydrophobic core of PTKs is strikingly different from other protein kinases, and PTK-specific variations in the core contribute to functional divergence by altering the stability and dynamics of the kinase domain. In particular, a functionally critical STK-conserved histidine that stabilizes the regulatory spine in STKs is selectively mutated to an alanine, serine or glutamate in PTKs, and this loss-of-function mutation is accommodated, in part, through compensatory PTK-specific interactions in the core. In particular, a PTK-conserved phenylalanine in the I-helix appears to structurally and functionally compensate for the loss of STK-histidine by interacting with the regulatory spine, which has far-reaching effects on enzyme activity, inhibitor sensing, and stability. We propose that hydrophobic core variations provide a selective advantage during PTK evolution by increasing the conformational flexibility, and therefore the allosteric potential of the kinase domain. Our studies also suggest that Tyrosine Kinase Like kinases such as RAF are intermediates in PTK evolutionary divergence inasmuch as they

  12. Triazole linkages and backbone branches in nucleic acids for biological and extra-biological applications

    NASA Astrophysics Data System (ADS)

    Paredes, Eduardo

    The recently increasing evidence of nucleic acids' alternative roles in biology and potential as useful nanomaterials and therapeutic agents has enabled the development of useful probes, elaborate nanostructures and therapeutic effectors based on nucleic acids. The study of alternative nucleic acid structure and function, particularly RNA, hinges on the ability to introduce site-specific modifications that either provide clues to the nucleic acid structure function relationship or alter the nucleic acid's function. Although the available chemistries allow for the conjugation of useful labels and molecules, their limitations lie in their tedious conjugation conditions or the lability of the installed probes. The development and optimization of click chemistry with RNA now provides the access to a robust and orthogonal conjugation methodology while providing stable conjugates. Our ability to introduce click reactive groups enzymatically, rather than only in the solid-phase, allows for the modification of larger, more cell relevant RNAs. Additionally, ligation of modified RNAs with larger RNA constructs through click chemistry represents an improvement over traditional ligation techniques. We determined that the triazole linkage generated through click chemistry is compatible in diverse nucleic acid based biological systems. Click chemistry has also been developed for extra-biological applications, particularly with DNA. We have expanded its use to generate useful polymer-DNA conjugates which can form controllable soft nanoparticles which take advantage of DNA's properties, i.e. DNA hybridization and computing. Additionally, we have generated protein-DNA conjugates and assembled protein-polymer hybrids mediated by DNA hybridization. The use of click chemistry in these reactions allows for the facile synthesis of these unnatural conjugates. We have also developed backbone branched DNA through click chemistry and showed that these branched DNAs are useful in generating

  13. An effective approach for alleviating cation-induced backbone degradation in aromatic ether-based alkaline polymer electrolytes.

    PubMed

    Han, Juanjuan; Liu, Qiong; Li, Xueqi; Pan, Jing; Wei, Ling; Wu, Ying; Peng, Hanqing; Wang, Ying; Li, Guangwei; Chen, Chen; Xiao, Li; Lu, Juntao; Zhuang, Lin

    2015-02-01

    Aromatic ether-based alkaline polymer electrolytes (APEs) are one of the most popular types of APEs being used in fuel cells. However, recent studies have demonstrated that upon being grafted by proximal cations some polar groups in the backbone of such APEs can be attacked by OH(-), leading to backbone degradation in an alkaline environment. To resolve this issue, we performed a systematic study on six APEs. We first replaced the polysulfone (PS) backbone with polyphenylsulfone (PPSU) and polyphenylether (PPO), whose molecular structures contain fewer polar groups. Although improved stability was seen after this change, cation-induced degradation was still obvious. Thus, our second move was to replace the ordinary quaternary ammonia (QA) cation, which had been closely attached to the polymer backbone, with a pendant-type QA (pQA), which was linked to the backbone through a long side chain. After a stability test in a 1 mol/L KOH solution at 80 °C for 30 days, all pQA-type APEs (pQAPS, pQAPPSU, and pQAPPO) exhibited as low as 8 wt % weight loss, which is close to the level of the bare backbone (5 wt %) and remarkably lower than those of the QA-type APEs (QAPS, QAPPSU, and QAPPO), whose weight losses under the same conditions were >30%. The pQA-type APEs also possessed clear microphase segregation morphology, which led to ionic conductivities that were higher, and water uptakes and degrees of membrane swelling that were lower, than those of the QA-type APEs. These observations unambiguously indicate that designing pendant-type cations is an effective approach to increasing the chemical stability of aromatic ether-based APEs. PMID:25594224

  14. Meter scale variation in shrub dominance and soil moisture structure Arctic arthropod communities

    PubMed Central

    Hansen, Oskar Liset Pryds; Bowden, Joseph J.; Treier, Urs A.; Normand, Signe; Høye, Toke

    2016-01-01

    The Arctic is warming at twice the rate of the rest of the world. This impacts Arctic species both directly, through increased temperatures, and indirectly, through structural changes in their habitats. Species are expected to exhibit idiosyncratic responses to structural change, which calls for detailed investigations at the species and community level. Here, we investigate how arthropod assemblages of spiders and beetles respond to variation in habitat structure at small spatial scales. We sampled transitions in shrub dominance and soil moisture between three different habitats (fen, dwarf shrub heath, and tall shrub tundra) at three different sites along a fjord gradient in southwest Greenland, using yellow pitfall cups. We identified 2,547 individuals belonging to 47 species. We used species richness estimation, indicator species analysis and latent variable modeling to examine differences in arthropod community structure in response to habitat variation at local (within site) and regional scales (between sites). We estimated species responses to the environment by fitting species-specific generalized linear models with environmental covariates. Species assemblages were segregated at the habitat and site level. Each habitat hosted significant indicator species, and species richness and diversity were significantly lower in fen habitats. Assemblage patterns were significantly linked to changes in soil moisture and vegetation height, as well as geographic location. We show that meter-scale variation among habitats affects arthropod community structure, supporting the notion that the Arctic tundra is a heterogeneous environment. To gain sufficient insight into temporal biodiversity change, we require studies of species distributions detailing species habitat preferences. PMID:27478709

  15. Meter scale variation in shrub dominance and soil moisture structure Arctic arthropod communities.

    PubMed

    Hansen, Rikke Reisner; Hansen, Oskar Liset Pryds; Bowden, Joseph J; Treier, Urs A; Normand, Signe; Høye, Toke

    2016-01-01

    The Arctic is warming at twice the rate of the rest of the world. This impacts Arctic species both directly, through increased temperatures, and indirectly, through structural changes in their habitats. Species are expected to exhibit idiosyncratic responses to structural change, which calls for detailed investigations at the species and community level. Here, we investigate how arthropod assemblages of spiders and beetles respond to variation in habitat structure at small spatial scales. We sampled transitions in shrub dominance and soil moisture between three different habitats (fen, dwarf shrub heath, and tall shrub tundra) at three different sites along a fjord gradient in southwest Greenland, using yellow pitfall cups. We identified 2,547 individuals belonging to 47 species. We used species richness estimation, indicator species analysis and latent variable modeling to examine differences in arthropod community structure in response to habitat variation at local (within site) and regional scales (between sites). We estimated species responses to the environment by fitting species-specific generalized linear models with environmental covariates. Species assemblages were segregated at the habitat and site level. Each habitat hosted significant indicator species, and species richness and diversity were significantly lower in fen habitats. Assemblage patterns were significantly linked to changes in soil moisture and vegetation height, as well as geographic location. We show that meter-scale variation among habitats affects arthropod community structure, supporting the notion that the Arctic tundra is a heterogeneous environment. To gain sufficient insight into temporal biodiversity change, we require studies of species distributions detailing species habitat preferences. PMID:27478709

  16. Spatial variations of the fine-structure constant in symmetron models

    NASA Astrophysics Data System (ADS)

    Silva, Marvin F.; Winther, Hans A.; Mota, David F.; Martins, C. J. A. P.

    2014-01-01

    We investigate the variation of the fine-structure constant, α, in symmetron models using N-body simulations in which the full spatial distribution of α at different redshifts has been calculated. In particular, we obtain simulated sky maps for this variation, and determine its power spectrum. We find that in high-density regions of space (such as deep inside dark matter halos) the value of α approaches the value measured on Earth. In the low-density outskirts of halos the scalar field value can approach the symmetry breaking value and leads to significantly different values of α. If the scalar-photon coupling strength βγ is of order unity we find that the variation of α inside dark matter halos can be of the same magnitude as the recent claims by Webb et al. of a dipole variation. Importantly, our results also show that with low-redshift symmetry breaking these models exhibit some dependence of α on lookback time (as opposed to a pure spatial dipole) which could in principle be detected by sufficiently accurate spectroscopic measurements, such as those of ALMA and the ELT-HIRES.

  17. Limit on the Temporal Variation of the Fine-Structure Constant Using Atomic Dysprosium

    SciTech Connect

    Cingoez, A.; Lapierre, A.; Leefer, N.; Nguyen, A.-T.; Lamoreaux, S. K.; Torgerson, J. R.; Budker, D.

    2007-01-26

    Over 8 months, we monitored transition frequencies between nearly degenerate, opposite-parity levels in two isotopes of atomic dysprosium (Dy). These frequencies are sensitive to variation of the fine-structure constant ({alpha}) due to relativistic corrections of opposite sign for the opposite-parity levels. In this unique system, in contrast to atomic-clock comparisons, the difference of the electronic energies of the opposite-parity levels can be monitored directly utilizing a rf electric-dipole transition between them. Our measurements show that the frequency variation of the 3.1-MHz transition in {sup 163}Dy and the 235-MHz transition in {sup 162}Dy are 9.0{+-}6.7 Hz/yr and -0.6{+-}6.5 Hz/yr, respectively. These results provide a rate of fractional variation of {alpha} of (-2.7{+-}2.6)x10{sup -15} yr{sup -1} (1{sigma}) without assumptions on constancy of other fundamental constants, indicating absence of significant variation at the present level of sensitivity.

  18. Line profiles variations from atmospheric eclipses: Constraints on the wind structure in Wolf-Rayet stars

    NASA Technical Reports Server (NTRS)

    Auer, L. H.; Koenigsberger, G.

    1994-01-01

    Binary systems in which one of the components has a stellar wind may present a phenomenon known as 'wind' or 'atmospheric eclipse', in which that wind occults the luminous disk of the companion. The enhanced absorption profile, relative to the spectrum at uneclipsed orbital phases, can be be modeled to yield constraints on the spatial structure of the eclipsing wind. A new, very efficient approach to the radiative transfer problem, which makes no requirements with respect to monotonicity of the velocity gradient or size of that gradient, is presented. The technique recovers both the comoving frame calculation and the Sobolev approximation in the appropiate limits. Sample computer simulations of the line profile variations induced by wind eclipses are presented. It is shown that the location of the wind absorption features in frequency is a diagnostic tool for identifying the size of the wind acceleration region. Comparison of the model profile variations with the observed variations in the Wolf-Rayet (W-R)+6 binary system V444 Cyg illustrate how the method can be used to derive information on the structure of the wind of the W-R star constrain the size of the W-R core radius.

  19. The variation of the fine-structure constant from disformal couplings

    NASA Astrophysics Data System (ADS)

    van de Bruck, Carsten; Mifsud, Jurgen; Nunes, Nelson J.

    2015-12-01

    We study a theory in which the electromagnetic field is disformally coupled to a scalar field, in addition to a usual non-minimal electromagnetic coupling. We show that disformal couplings modify the expression for the fine-structure constant, α. As a result, the theory we consider can explain the non-zero reported variation in the evolution of α by purely considering disformal couplings. We also find that if matter and photons are coupled in the same way to the scalar field, disformal couplings itself do not lead to a variation of the fine-structure constant. A number of scenarios are discussed consistent with the current astrophysical, geochemical, laboratory and the cosmic microwave background radiation constraints on the cosmological evolution of α. The models presented are also consistent with the current type Ia supernovae constraints on the effective dark energy equation of state. We find that the Oklo bound in particular puts strong constraints on the model parameters. From our numerical results, we find that the introduction of a non-minimal electromagnetic coupling enhances the cosmological variation in α. Better constrained data is expected to be reported by ALMA and with the forthcoming generation of high-resolution ultra-stable spectrographs such as PEPSI, ESPRESSO, and ELT-HIRES. Furthermore, an expected increase in the sensitivity of molecular and nuclear clocks will put a more stringent constraint on the theory.

  20. Normal Variations of Sphenoid Sinus and the Adjacent Structures Detected in Cone Beam Computed Tomography

    PubMed Central

    Rahmati, Azadeh; Ghafari, Roshanak; AnjomShoa, Maryam

    2016-01-01

    Statement of the Problem The sphenoid sinus is a common target of paranasal surgery. Functional endoscopic sinus surgery is likely to endanger the anatomic variations of vital structures adjacent to the sphenoid sinus. Purpose The aim of this study was to determine the variations of sphenoid sinus and the related structures by using cone-beam computed tomography (CBCT). Materials and Method In this descriptive-analytic study, CBCT images of 103 patients aged above 20-years were selected (206 sides). Degree of pneumatization of sphenoid sinus, pneumatization of the anterior clinoid process, pterygoid process, protrusion of optic canal, vidian canal, and foramen rotundum, as well as prevalence of sinus septa were recorded. Examinations were performed using On-Demand software (Version 1); data were analyzed by using chi-square test. Results There was a statistically significant correlation between the pterygoid pneumatization and vidian canal protrusion (p< 0.001), and foramen rotundum protrusion (p< 0.001). The optic canal protrusion was found to be significantly associated with the anterior clinoid pneumatization and pterygoid process (p< 0.001). Statistically significant relationship was also observed between the carotid canal protrusion and pterygoid process pneumatization (p< 0.001). Conclusion The anatomical variations of the sphenoid sinus tend to give rise to a complexity of symptoms and potentially serious complications. This variability necessitates a comprehensive understanding of the regional sphenoid sinus anatomy by a detailed CBCT sinus examination. PMID:26966706

  1. Iterative image reconstruction for multienergy computed tomography via structure tensor total variation regularization

    NASA Astrophysics Data System (ADS)

    Zeng, Dong; Bian, Zhaoying; Gong, Changfei; Huang, Jing; He, Ji; Zhang, Hua; Lu, Lijun; Feng, Qianjin; Liang, Zhengrong; Ma, Jianhua

    2016-03-01

    Multienergy computed tomography (MECT) has the potential to simultaneously offer multiple sets of energy- selective data belonging to specific energy windows. However, because sufficient photon counts are not available in the specific energy windows compared with that in the whole energy window, the MECT images reconstructed by the analytical approach often suffer from poor signal-to-noise (SNR) and strong streak artifacts. To eliminate this drawback, in this work we present a penalized weighted least-squares (PWLS) scheme by incorporating the new concept of structure tensor total variation (STV) regularization to improve the MECT images quality from low-milliampere-seconds (low-mAs) data acquisitions. Henceforth the present scheme is referred to as `PWLS- STV' for simplicity. Specifically, the STV regularization is derived by penalizing the eigenvalues of the structure tensor of every point in the MECT images. Thus it can provide more robust measures of image variation, which can eliminate the patchy artifacts often observed in total variation regularization. Subsequently, an alternating optimization algorithm was adopted to minimize the objective function. Experiments with a digital XCAT phantom clearly demonstrate that the present PWLS-STV algorithm can achieve more gains than the existing TV-based algorithms and the conventional filtered backpeojection (FBP) algorithm in terms of noise-induced artifacts suppression, resolution preservation, and material decomposition assessment.

  2. Polar front associated variation in prokaryotic community structure in Arctic shelf seafloor

    PubMed Central

    Nguyen, Tan T.; Landfald, Bjarne

    2015-01-01

    Spatial variations in composition of marine microbial communities and its causes have largely been disclosed in studies comprising rather large environmental and spatial differences. In the present study, we explored if a moderate but temporally permanent climatic division within a contiguous arctic shelf seafloor was traceable in the diversity patterns of its bacterial and archaeal communities. Soft bottom sediment samples were collected at 10 geographical locations, spanning spatial distances of up to 640 km, transecting the oceanic polar front in the Barents Sea. The northern sampling sites were generally colder, less saline, shallower, and showed higher concentrations of freshly sedimented phytopigments compared to the southern study locations. Sampling sites depicted low variation in relative abundances of taxa at class level, with persistent numerical dominance by lineages of Gamma- and Deltaproteobacteria (57–66% of bacterial sequence reads). The Archaea, which constituted 0.7–1.8% of 16S rRNA gene copy numbers in the sediment, were overwhelmingly (85.8%) affiliated with the Thaumarchaeota. Beta-diversity analyses showed the environmental variations throughout the sampling range to have a stronger impact on the structuring of both the bacterial and archaeal communities than spatial effects. While bacterial communities were significantly influenced by the combined effect of several weakly selective environmental differences, including temperature, archaeal communities appeared to be more uniquely structured by the level of freshly sedimented phytopigments. PMID:25667586

  3. Microsatellite variation in the yellowhammer Emberiza citrinella: population structure of a declining farmland bird.

    PubMed

    Lee, P L; Bradbury, R B; Wilson, J D; Flanagan, N S; Richardson, L; Perkins, A J; Krebs, J R

    2001-07-01

    In recent years, there has been much concern in the UK about population declines of widespread species in agricultural habitats. Conservation-orientated research on declining birds has focused on vital rates of survival and productivity. However, the environmental factors which may influence movements between populations of widespread species is poorly understood. Population genetic structure is an indirect description of dispersal between groups of individuals. To attempt to develop an understanding of genetic structuring in a widespread, but declining, farmland bird, we therefore investigated the yellowhammer, Emberiza citrinella, population in England and Wales using microsatellite data. Our first aim was to investigate whether there was genetic substructuring in the population. A second aim was to investigate if there was a relationship between genetic distances and various environmental variables. Finally, we analysed the microsatellite data for evidence of loss of genetic variation due to population decline. Our data showed a slight but significant structure within the yellowhammer population. This therefore cannot be considered a panmictic population. Our example from South Cumbria implies that high-altitude barriers may have a slight influence on population structure. However, on the whole, genetic distances between sample sites were not significantly correlated with geographical distances, degrees of population connectivity, high altitudes, or differences in precipitation between sites. Finally, we detected departures from mutation-drift equilibrium (excess heterozygosity), which is indicative of a loss of genetic variation through recent decline. PMID:11472532

  4. Sulfation and cation effects on the conformational properties of the glycan backbone of chondroitin sulfate disaccharides.

    PubMed

    Faller, Christina E; Guvench, Olgun

    2015-05-21

    Chondroitin sulfate (CS) is one of several glycosaminoglycans that are major components of proteoglycans. A linear polymer consisting of repeats of the disaccharide -4GlcAβ1-3GalNAcβ1-, CS undergoes differential sulfation resulting in five unique sulfation patterns. Because of the dimer repeat, the CS glycosidic "backbone" has two distinct sets of conformational degrees of freedom defined by pairs of dihedral angles: (ϕ1, ψ1) about the β1-3 glycosidic linkage and (ϕ2, ψ2) about the β1-4 glycosidic linkage. Differential sulfation and the possibility of cation binding, combined with the conformational flexibility and biological diversity of CS, complicate experimental efforts to understand CS three-dimensional structures at atomic resolution. Therefore, all-atom explicit-solvent molecular dynamics simulations with Adaptive Biasing Force sampling of the CS backbone were applied to obtain high-resolution, high-precision free energies of CS disaccharides as a function of all possible backbone geometries. All 10 disaccharides (β1-3 vs β1-4 linkage × five different sulfation patterns) were studied; additionally, ion effects were investigated by considering each disaccharide in the presence of either neutralizing sodium or calcium cations. GlcAβ1-3GalNAc disaccharides have a single, broad, thermodynamically important free-energy minimum, whereas GalNAcβ1-4GlcA disaccharides have two such minima. Calcium cations but not sodium cations bind to the disaccharides, and binding is primarily to the GlcA -COO(-) moiety as opposed to sulfate groups. This binding alters the glycan backbone thermodynamics in instances where a calcium cation bound to -COO(-) can act to bridge and stabilize an interaction with an adjacent sulfate group, whereas, in the absence of this cation, the proximity of a sulfate group to -COO(-) results in two like charges being both desolvated and placed adjacent to each other and is found to be destabilizing. In addition to providing information

  5. Site-Specific Structural Variations Accompanying Tubular Assembly of the HIV-1 Capsid Protein

    PubMed Central

    Bayro, Marvin J.; Chen, Bo; Yau, Wai-Ming; Tycko, Robert

    2014-01-01

    The 231-residue capsid (CA) protein of HIV-1 spontaneously self-assembles into tubes with a hexagonal lattice that is believed to mimic the surface lattice of conical capsid cores within intact virions. We report the results of solid state nuclear magnetic resonance (NMR) measurements on HIV-1 CA tubes that provide new information regarding changes in molecular structure that accompany CA self-assembly, local dynamics within CA tubes, and possible mechanisms for the generation of lattice curvature. This information is contained in site-specific assignments of signals in two- and three-dimensional solid state NMR spectra, conformation-dependent 15N and 13C NMR chemical shifts, detection of highly dynamic residues under solution NMR conditions, measurements of local variations in transverse spin relaxation rates of amide 1H nuclei, and quantitative measurements of site-specific 15N-15N dipole-dipole couplings. Our data show that most of the CA sequence is conformationally ordered and relatively rigid in tubular assemblies and that the structures of N-terminal and C-terminal domains (NTD and CTD) observed in solution are largely retained. However, specific segments, including the N-terminal β-hairpin, the cyclophilin A binding loop, the inter-domain linker, segments involved in intermolecular NTD-CTD interactions, and the C-terminal tail, have substantial static or dynamical disorder in tubular assemblies. Other segments, including the 310-helical segment in CTD, undergo clear conformational changes. Structural variations associated with curvature of the CA lattice appear to be localized in the inter-domain linker and intermolecular NTD-CTD interface, while structural variations within NTD hexamers, around local three-fold symmetry axes, and in CTD-CTD dimerization interfaces are less significant. PMID:24370930

  6. Highly charged ions for atomic clocks and search for variation of the fine structure constant

    NASA Astrophysics Data System (ADS)

    Dzuba, V. A.; Flambaum, V. V.

    2015-11-01

    We review a number of highly charged ions which have optical transitions suitable for building extremely accurate atomic clocks. This includes ions from Hf 12+ to U 34+, which have the 4 f 12 configuration of valence electrons, the Ir 17+ ion, which has a hole in almost filled 4 f subshell, the Ho 14+, Cf 15+, Es 17+ and Es 16+ ions. Clock transitions in most of these ions are sensitive to variation of the fine structure constant, α (α = e2/hbar c). E.g., californium and einsteinium ions have largest known sensitivity to α-variation while holmium ion looks as the most suitable ion for experimental study. We study the spectra of the ions and their features relevant to the use as frequency standards.

  7. Enhanced sensitivity to the fine-structure-constant variation in the Th IV atomic clock transition

    SciTech Connect

    Flambaum, V. V.; Porsev, S. G.

    2009-12-15

    Our calculations have shown that the 5f{sub 5/2}-7s{sub 1/2} 23 131 cm{sup -1} transition from the ground state in the ion Th{sup 3+} is very sensitive to the temporal variation of the fine-structure constant alpha=e{sup 2}/(Planck constant/2pi)c (q=-75 300 cm{sup -1}). The line is very narrow, the ion has been trapped and laser cooled, and the positive shifter line 5f{sub 5/2}-5f{sub 7/2} 4325 cm{sup -1} (q=+2900 cm{sup -1}) may be used as a reference. A comparison may also be made with a positive shifter in another atom or ion. This makes Th{sup 3+} a good candidate to search for the alpha variation.

  8. Variational-method-based higher order mode analysis extendible to realistic tapered disk-loaded structures

    NASA Astrophysics Data System (ADS)

    Wang, L. F.; Lin, Y. Z.; Higo, T.

    2002-04-01

    In order to obtain high luminosity and energy efficiency in future linear colliders, most designs for e + and e - collisions in the TeV range will use multi-bunch operation. Therefore, the study of higher order modes excited by previous bunches in the train becomes very important for the optimal design of the accelerator components. Many designs have used tapered disk-loaded waveguides for acceleration. Various numerical methods have been used for the modal analysis of the structure. In this paper, a high-precision eigenmode-computation analysis based on a variational method will be discussed. It allows for rounding the edge of a disk hole without any approximation in shape treatment and calculates the exactly synchronous modes. It converges much faster than the mesh-based computer code SUPERFISH. Good agreement was observed between the results of the variational method and those of other methods.

  9. The latitude-height structure of 40-50 day variations in atmospheric angular momentum

    NASA Technical Reports Server (NTRS)

    Anderson, J. R.; Rosen, R. D.

    1983-01-01

    Using five years of U.S. National Meteorological Center twice-daily global analyses, a description of the two-dimensional latitude-height structure of the winds responsible for quasi-periodic variations in the relative angular momentum of the atmosphere observed by Langley et al. (1981) is constructed. Cross-spectral and amplitude phase eigenvector techniques indicate that these variations are associated with wave-like motions in the tropical upper troposphere which propagate poleward and downward in phase within the tropics. The tropical component is suggested to be the zonally averaged part of the motions described by Madden and Julian (1971, 1972), while a Northern Hemisphere midlatitude component whose phase is essentially independent of height may be a direct response to the tropical motions. Alternatively, both motions may be the common response to an as yet unidentified tropical forcing.

  10. Variation Principles and Applications in the Study of Cell Structure and Aging

    NASA Technical Reports Server (NTRS)

    Economos, Angelos C.; Miquel, Jaime; Ballard, Ralph C.; Johnson, John E., Jr.

    1981-01-01

    In this report we have attempted to show that "some reality lies concealed in biological variation". This "reality" has its principles, laws, mechanisms, and rules, only a few of which we have sketched. A related idea we pursued was that important information may be lost in the process of ignoring frequency distributions of physiological variables (as is customary in experimental physiology and gerontology). We suggested that it may be advantageous to expand one's "statistical field of vision" beyond simple averages +/- standard deviations. Indeed, frequency distribution analysis may make visible some hidden information not evident from a simple qualitative analysis, particularly when the effect of some external factor or condition (e.g., aging, dietary chemicals) is being investigated. This was clearly illustrated by the application of distribution analysis in the study of variation in mouse liver cellular and fine structure, and may be true of fine structural studies in general. In living systems, structure and function interact in a dynamic way; they are "inseparable," unlike in technological systems or machines. Changes in fine structure therefore reflect changes in function. If such changes do not exceed a certain physiologic range, a quantitative analysis of structure will provide valuable information on quantitative changes in function that may not be possible or easy to measure directly. Because there is a large inherent variation in fine structure of cells in a given organ of an individual and among individuals, changes in fine structure can be analyzed only by studying frequency distribution curves of various structural characteristics (dimensions). Simple averages +/- S.D. do not in general reveal all information on the effect of a certain factor, because often this effect is not uniform; on the contrary, this will be apparent from distribution analysis because the form of the curves will be affected. We have also attempted to show in this chapter that

  11. Seasonal and spatial variations in fish and macrocrustacean assemblage structure in Mad Island Marsh estuary, Texas

    NASA Astrophysics Data System (ADS)

    Akin, S.; Winemiller, K. O.; Gelwick, F. P.

    2003-05-01

    Fish and macrocrustacean assemblage structure was analyzed along an estuarine gradient at Mad Island Marsh (MIM), Matagorda Bay, TX, during March 1998-August 1999. Eight estuarine-dependent fish species accounted for 94% of the individual fishes collected, and three species accounted for 96% of macrocrustacean abundance. Consistent with evidence from other Gulf of Mexico estuarine studies, species richness and abundance were highest during late spring and summer, and lowest during winter and early spring. Sites near the bay supported the most individuals and species. Associations between fish abundance and environmental variables were examined with canonical correspondence analysis. The dominant gradient was associated with water depth and distance from the bay. The secondary gradient reflected seasonal variation and was associated with temperature, salinity, dissolved oxygen, and vegetation cover. At the scales examined, estuarine biota responded to seasonal variation more than spatial variation. Estuarine-dependent species dominated the fauna and were common throughout the open waters of the shallow lake during winter-early spring when water temperature and salinity were low and dissolved oxygen high. During summer-early fall, sub-optimal environmental conditions (high temperature, low DO) in upper reaches accounted for strong spatial variation in assemblage composition. Small estuarine-resident fishes and the blue crab ( Callinectes sapidus) were common in warm, shallow, vegetated inland sites during summer-fall. Estuarine-dependent species were common at deeper, more saline locations near the bay during this period. During summer, freshwater species, such as gizzard shad ( Dorosoma cepedianum) and gars ( Lepisosteus spp.), were positively associated with water depth and proximity to the bay. The distribution and abundance of fishes in MIM appear to result from the combined effects of endogenous, seasonal patterns of reproduction and migration operating on large

  12. RNA backbone: consensus all-angle conformers and modular string nomenclature (an RNA Ontology Consortium contribution).

    PubMed

    Richardson, Jane S; Schneider, Bohdan; Murray, Laura W; Kapral, Gary J; Immormino, Robert M; Headd, Jeffrey J; Richardson, David C; Ham, Daniela; Hershkovits, Eli; Williams, Loren Dean; Keating, Kevin S; Pyle, Anna Marie; Micallef, David; Westbrook, John; Berman, Helen M

    2008-03-01

    A consensus classification and nomenclature are defined for RNA backbone structure using all of the backbone torsion angles. By a consensus of several independent analysis methods, 46 discrete conformers are identified as suitably clustered in a quality-filtered, multidimensional dihedral angle distribution. Most of these conformers represent identifiable features or roles within RNA structures. The conformers are given two-character names that reflect the seven-angle delta epsilon zeta alpha beta gamma delta combinations empirically found favorable for the sugar-to-sugar "suite" unit within which the angle correlations are strongest (e.g., 1a for A-form, 5z for the start of S-motifs). Since the half-nucleotides are specified by a number for delta epsilon zeta and a lowercase letter for alpha beta gamma delta, this modular system can also be parsed to describe traditional nucleotide units (e.g., a1) or the dinucleotides (e.g., a1a1) that are especially useful at the level of crystallographic map fitting. This nomenclature can also be written as a string with two-character suite names between the uppercase letters of the base sequence (N1aG1gN1aR1aA1cN1a for a GNRA tetraloop), facilitating bioinformatic comparisons. Cluster means, standard deviations, coordinates, and examples are made available, as well as the Suitename software that assigns suite conformer names and conformer match quality (suiteness) from atomic coordinates. The RNA Ontology Consortium will combine this new backbone system with others that define base pairs, base-stacking, and hydrogen-bond relationships to provide a full description of RNA structural motifs. PMID:18192612

  13. Paired-Duplication Signatures Mark Cryptic Inversions and Other Complex Structural Variation

    PubMed Central

    Brand, Harrison; Collins, Ryan L.; Hanscom, Carrie; Rosenfeld, Jill A.; Pillalamarri, Vamsee; Stone, Matthew R.; Kelley, Fontina; Mason, Tamara; Margolin, Lauren; Eggert, Stacey; Mitchell, Elyse; Hodge, Jennelle C.; Gusella, James F.; Sanders, Stephan J.; Talkowski, Michael E.

    2015-01-01

    Copy-number variants (CNVs) have been the predominant focus of genetic studies of structural variation, and chromosomal microarray (CMA) for genome-wide CNV detection is the recommended first-tier genetic diagnostic screen in neurodevelopmental disorders. We compared CNVs observed by CMA to the structural variation detected by whole-genome large-insert sequencing in 259 individuals diagnosed with autism spectrum disorder (ASD) from the Simons Simplex Collection. These analyses revealed a diverse landscape of complex duplications in the human genome. One remarkably common class of complex rearrangement, which we term dupINVdup, involves two closely located duplications (“paired duplications”) that flank the breakpoints of an inversion. This complex variant class is cryptic to CMA, but we observed it in 8.1% of all subjects. We also detected other paired-duplication signatures and duplication-mediated complex rearrangements in 15.8% of all ASD subjects. Breakpoint analysis showed that the predominant mechanism of formation of these complex duplication-associated variants was microhomology-mediated repair. On the basis of the striking prevalence of dupINVdups in this cohort, we explored the landscape of all inversion variation among the 235 highest-quality libraries and found abundant complexity among these variants: only 39.3% of inversions were canonical, or simple, inversions without additional rearrangement. Collectively, these findings indicate that dupINVdups, as well as other complex duplication-associated rearrangements, represent relatively common sources of genomic variation that is cryptic to population-based microarray and low-depth whole-genome sequencing. They also suggest that paired-duplication signatures detected by CMA warrant further scrutiny in genetic diagnostic testing given that they might mark complex rearrangements of potential clinical relevance. PMID:26094575

  14. Prediction of individual differences in risky behavior in young adults via variations in local brain structure

    PubMed Central

    Nasiriavanaki, Zahra; ArianNik, Mohsen; Abbassian, Abdolhosein; Mahmoudi, Elham; Roufigari, Neda; Shahzadi, Sohrab; Nasiriavanaki, Mohammadreza; Bahrami, Bahador

    2015-01-01

    In recent years the problem of how inter-individual differences play a role in risk-taking behavior has become a much debated issue. We investigated this problem based on the well-known balloon analog risk task (BART) in 48 healthy subjects in which participants inflate a virtual balloon opting for a higher score in the face of a riskier chance of the balloon explosion. In this study, based on a structural Voxel Based Morphometry (VBM) technique we demonstrate a significant positive correlation between BART score and size of the gray matter volume in the anterior insula in riskier subjects. Although the anterior insula is among the candidate brain areas that were involved in the risk taking behavior in fMRI studies, here based on our structural data it is the only area that was significantly related to structural variation among different subjects. PMID:26500482

  15. CONSTRAINTS ON SPATIAL VARIATIONS IN THE FINE-STRUCTURE CONSTANT FROM PLANCK

    SciTech Connect

    O'Bryan, Jon; Smidt, Joseph; De Bernardis, Francesco; Cooray, Asantha

    2015-01-01

    We use the cosmic microwave background (CMB) anisotropy data from Planck to constrain the spatial fluctuations of the fine-structure constant α at a redshift of 1100. We use a quadratic estimator to measure the four-point correlation function of the CMB temperature anisotropies and extract the angular power spectrum fine-structure constant spatial variations projected along the line of sight at the last scattering surface. At tens of degree angular scales and above, we constrain the fractional rms fluctuations of the fine-structure constant to be (δα/α){sub rms} < 3.4 × 10{sup –3} at the 68% confidence level. We find no evidence for a spatially varying α at a redshift of 10{sup 3}.

  16. From Structural Variation of Gene Molecules to Chromatin Dynamics and Transcriptional Bursting

    PubMed Central

    Boeger, Hinrich; Shelansky, Robert; Patel, Heta; Brown, Christopher R.

    2015-01-01

    Transcriptional activation of eukaryotic genes is accompanied, in general, by a change in the sensitivity of promoter chromatin to endonucleases. The structural basis of this alteration has remained elusive for decades; but the change has been viewed as a transformation of one structure into another, from “closed” to “open” chromatin. In contradistinction to this static and deterministic view of the problem, a dynamical and probabilistic theory of promoter chromatin has emerged as its solution. This theory, which we review here, explains observed variation in promoter chromatin structure at the level of single gene molecules and provides a molecular basis for random bursting in transcription—the conjecture that promoters stochastically transition between transcriptionally conducive and inconducive states. The mechanism of transcriptional regulation may be understood only in probabilistic terms. PMID:26136240

  17. Real-time aircraft structural damage identification with flight condition variations

    NASA Astrophysics Data System (ADS)

    Lew, Jiann-Shiun; Loh, Chin-Hsiung

    2012-04-01

    This paper presents a real-time structural damage identification method for aircraft with flight condition variations. The proposed approach begins by identifying the dynamic models under various test conditions from time-domain input/output data. A singular value decomposition technique is then used to characterize and quantify the parameter uncertainties from the identified models. The uncertainty coordinates, corresponding to the identified principal directions, of the identified models are computed, and the residual errors between the identified uncertainty coordinates and the estimated uncertainty coordinates of the health structure are used to identify damage status. A correlation approach is applied to identify damage type and intensity, based on the difference between the identified parameters and the estimated parameters of the healthy structure. The proposed approach is demonstrated by application to the Benchmark Active Controls Technology (BACT) wind-tunnel model.

  18. Conformation-dependent backbone geometry restraints set a new standard for protein crystallographic refinement

    SciTech Connect

    Moriarty, Nigel W.; Tronrud, Dale E.; Adams, Paul D.; Karplus, P. Andrew

    2014-06-17

    Ideal values of bond angles and lengths used as external restraints are crucial for the successful refinement of protein crystal structures at all but the highest of resolutions. The restraints in common usage today have been designed based on the assumption that each type of bond or angle has a single ideal value independent of context. However, recent work has shown that the ideal values are, in fact, sensitive to local conformation, and as a first step toward using such information to build more accurate models, ultra-high resolution protein crystal structures have been used to derive a conformation-dependent library (CDL) of restraints for the protein backbone (Berkholz et al. 2009. Structure. 17, 1316). Here, we report the introduction of this CDL into the Phenix package and the results of test refinements of thousands of structures across a wide range of resolutions. These tests show that use of the conformation dependent library yields models that have substantially better agreement with ideal main-chain bond angles and lengths and, on average, a slightly enhanced fit to the X-ray data. No disadvantages of using the backbone CDL are apparent. In Phenix usage of the CDL can be selected by simply specifying the cdl=True option. This successful implementation paves the way for further aspects of the context-dependence of ideal geometry to be characterized and applied to improve experimental and predictive modelling accuracy.

  19. Conformation-dependent backbone geometry restraints set a new standard for protein crystallographic refinement

    DOE PAGESBeta

    Moriarty, Nigel W.; Tronrud, Dale E.; Adams, Paul D.; Karplus, P. Andrew

    2014-06-17

    Ideal values of bond angles and lengths used as external restraints are crucial for the successful refinement of protein crystal structures at all but the highest of resolutions. The restraints in common usage today have been designed based on the assumption that each type of bond or angle has a single ideal value independent of context. However, recent work has shown that the ideal values are, in fact, sensitive to local conformation, and as a first step toward using such information to build more accurate models, ultra-high resolution protein crystal structures have been used to derive a conformation-dependent library (CDL)more » of restraints for the protein backbone (Berkholz et al. 2009. Structure. 17, 1316). Here, we report the introduction of this CDL into the Phenix package and the results of test refinements of thousands of structures across a wide range of resolutions. These tests show that use of the conformation dependent library yields models that have substantially better agreement with ideal main-chain bond angles and lengths and, on average, a slightly enhanced fit to the X-ray data. No disadvantages of using the backbone CDL are apparent. In Phenix usage of the CDL can be selected by simply specifying the cdl=True option. This successful implementation paves the way for further aspects of the context-dependence of ideal geometry to be characterized and applied to improve experimental and predictive modelling accuracy.« less

  20. Conformation-dependent backbone geometry restraints set a new standard for protein crystallographic refinement

    PubMed Central

    Moriarty, Nigel W.; Tronrud, Dale E.; Adams, Paul D.; Karplus, P. Andrew

    2014-01-01

    Ideal values of bond angles and lengths used as external restraints are crucial for the successful refinement of protein crystal structures at all but the highest of resolutions. The restraints in common usage today have been designed based on the assumption that each type of bond or angle has a single ideal value independent of context. However, recent work has shown that the ideal values are, in fact, sensitive to local conformation, and as a first step toward using such information to build more accurate models, ultra-high resolution protein crystal structures have been used to derive a conformation-dependent library (CDL) of restraints for the protein backbone (Berkholz et al. 2009. Structure. 17, 1316). Here, we report the introduction of this CDL into the Phenix package and the results of test refinements of thousands of structures across a wide range of resolutions. These tests show that use of the conformation dependent library yields models that have substantially better agreement with ideal main-chain bond angles and lengths and, on average, a slightly enhanced fit to the X-ray data. No disadvantages of using the backbone CDL are apparent. In Phenix usage of the CDL can be selected by simply specifying the cdl=True option. This successful implementation paves the way for further aspects of the context-dependence of ideal geometry to be characterized and applied to improve experimental and predictive modelling accuracy. PMID:24890778

  1. Colloidal quantum dot lasers built on a passive two-dimensional photonic crystal backbone.

    PubMed

    Chang, Hojun; Min, Kyungtaek; Lee, Myungjae; Kang, Minsu; Park, Yeonsang; Cho, Kyung-Sang; Roh, Young-Geun; Woo Hwang, Sung; Jeon, Heonsu

    2016-03-17

    We report the room-temperature lasing action from two-dimensional photonic crystal (PC) structures composed of a passive Si3N4 backbone with an over-coat of CdSe/CdS/ZnS colloidal quantum dots (CQDs) for optical gain. When optically excited, devices lased in dual PC band-edge modes, with the modal dominance governed by the thickness of the CQD over-layer. The demonstrated laser platform should have an impact on future photonic integrated circuits as the on-chip coupling between active and passive components is readily achievable. PMID:26935411

  2. Determination of backbone nitrogen-nitrogen J correlations in proteins.

    PubMed

    Theis, K; Dingley, A J; Hoffmann, A; Omichinski, J G; Grzesiek, S

    1997-12-01

    Recently, a quantitative J correlation technique has been presented which makes use of homonuclear Hartmann-Hahn cross-polarization (TOCSY) to measure (3)J(C)'(C)' in proteins isotopically enriched with (13)C [Grzesiek, S. and Bax, A. (1997) J. Biomol. NMR, 9, 207-211]. Since homonuclear Hartmann-Hahn is twice as fast as conventional COSY transfer, this method is much less sensitive to transverse relaxation, which is the principal limiting factor in achieving long-range J-coupling correlations in macromolecules. Here we describe a similar experiment which is used to measure(3) J(NN) coupling constants between sequential amide(15) N nuclei in the backbone of ubiquitin. As expected from the low magnetic moment of (15)N, the (3)J(NN) coupling constants are exceedingly small, with values between 0.14 and 0.36 Hz for residues in β-conformations and values below 0.15 Hz for residues in α-conformations. In contrast to what is expected from a Karplus-type dependence on the backbone angle ψ, large differences in the values of(3) J(NN) are observed for a number of residues with very similar backbone ψ angles. A quantitative description of statistical and systematic errors, in particular of relaxation effects during the TOCSY transfer, shows that these differences are highly significant. PMID:20859784

  3. Variations of structural components: specific intercultural differences in facial morphology, skin type, and structures.

    PubMed

    McKnight, Aisha; Momoh, Adeyiza O; Bullocks, Jamal M

    2009-08-01

    Analysis of the differences in facial morphology and skin structure and tone among ethnic groups within the realm of plastic surgery is relevant due to the increasing number of ethnic individuals seeking cosmetic surgery. Previous classifications of ideal facial morphologic characteristics have been revised and challenged over the years to accurately reflect the differences in facial structure that are aesthetically pleasing to individuals of differing ethnic groups. The traditional neoclassic canons reflected the European Caucasian facial morphology and cannot be used to classify facial characteristics in ethnic groups due to drastic differences in measurement and proportion. In addition, differences in biophysiologic properties of ethnic skin types influence the progression of aging and the ability of skin to withstand environmental insults. Thickness of the stratum corneum, water content, and melanin composition are important factors that were analyzed in varying ethnic groups. Although it appears that Caucasian Americans are subject to earlier onset of skin wrinkling and sagging than are African Americans due to thinner stratum corneum layers and decreased water content, more research needs to be conducted to be inclusive of other ethnic groups. These data will enable plastic surgeons to treat these groups more effectively while preserving their unique characteristics. PMID:20676309

  4. Beyond sex differences: new approaches for thinking about variation in brain structure and function.

    PubMed

    Joel, Daphna; Fausto-Sterling, Anne

    2016-02-19

    In the study of variation in brain structure and function that might relate to sex and gender, language matters because it frames our research questions and methods. In this article, we offer an approach to thinking about variation in brain structure and function that pulls us outside the sex differences formulation. We argue that the existence of differences between the brains of males and females does not unravel the relations between sex and the brain nor is it sufficient to characterize a population of brains. Such characterization is necessary for studying sex effects on the brain as well as for studying brain structure and function in general. Animal studies show that sex interacts with environmental, developmental and genetic factors to affect the brain. Studies of humans further suggest that human brains are better described as belonging to a single heterogeneous population rather than two distinct populations. We discuss the implications of these observations for studies of brain and behaviour in humans and in laboratory animals. We believe that studying sex effects in context and developing or adopting analytical methods that take into account the heterogeneity of the brain are crucial for the advancement of human health and well-being. PMID:26833844

  5. Variation in multiring basic structures as a function of impact angle

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

    Previous studies have demonstrated that the impact process in the laboratory varies as a function of impact angle. This variation is attributed to changes in energy partitioning and projectile failure during the impact and, in simple craters, produces a sequence of progressively smaller and more asymmetric crater forms as impact angle decreases from approximately 20 degrees. Variations in impact angle can produce differences in the appearance of multiring impact basins. Comparisons of Orientale to the more oblique impact structure at Crisium also suggests that these differences primarily reflect the degree of cavity collapse. The relative changes in massif ring topography, basin scarp relief, and the distribution of peripheral mare units are consistent with a reduction in degree of cavity collapse with decreasing impact angle. The prominent uprange basin scarps and the restriction of tectonically derived peripheral mare units along uprange ring structures also may indicate an uprange enhancement of failure during cavity collapse. Finally, although basin ring faults appear to be preferred pathways for mare volcanism, fault-controlled peripheral mare volcanism occurs most readily uprange of an oblique impact; elsewhere such volcanism apparently requires superposition of an impact structure on the ring fault.

  6. Natural Genetic Variation of Arabidopsis thaliana Is Geographically Structured in the Iberian Peninsula

    PubMed Central

    Picó, F. Xavier; Méndez-Vigo, Belén; Martínez-Zapater, José M.; Alonso-Blanco, Carlos

    2008-01-01

    To understand the demographic history of Arabidopsis thaliana within its native geographical range, we have studied its genetic structure in the Iberian Peninsula region. We have analyzed the amount and spatial distribution of A. thaliana genetic variation by genotyping 268 individuals sampled in 100 natural populations from the Iberian Peninsula. Analyses of 175 individuals from 7 of these populations, with 20 chloroplast and nuclear microsatellite loci and 109 common single nucleotide polymorphisms, show significant population differentiation and isolation by distance. In addition, analyses of one genotype from 100 populations detected significant isolation by distance over the entire Iberian Peninsula, as well as among six Iberian subregions. Analyses of these 100 genotypes with different model-based clustering algorithms inferred four genetic clusters, which show a clear-cut geographical differentiation pattern. On the other hand, clustering analysis of a worldwide sample showed a west–east Eurasian longitudinal spatial gradient of the commonest Iberian genetic cluster. These results indicate that A. thaliana genetic variation displays significant regional structure and consistently support the hypothesis that Iberia has been a glacial refugium for A. thaliana. Furthermore, the Iberian geographical structure indicates a complex regional population dynamics, suggesting that this region contained multiple Pleistocene refugia with a different contribution to the postglacial colonization of Europe. PMID:18716334

  7. Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia

    PubMed Central

    Callicott, Joseph H.; Straub, Richard E.; Pezawas, Lukas; Egan, Michael F.; Mattay, Venkata S.; Hariri, Ahmad R.; Verchinski, Beth A.; Meyer-Lindenberg, Andreas; Balkissoon, Rishi; Kolachana, Bhaskar; Goldberg, Terry E.; Weinberger, Daniel R.

    2005-01-01

    Disrupted-in-schizophrenia 1 (DISC1) is a promising schizophrenia candidate gene expressed predominantly within the hippocampus. We typed 12 single-nucleotide polymorphisms (SNPs) that covered the DISC1 gene. A three-SNP haplotype [hCV219779 (C)-rs821597 (G)-rs821616 (A)] spanning 83 kb of the gene was associated with schizophrenia in a family-based sample (P = 0.002). A common nonconservative SNP (Ser704Cys) (rs821616) within this haplotype was associated with schizophrenia (P = 0.004). Based on primary expression of DISC1 in hippocampus, we hypothesized that allelic variation at Ser704Cys would have a measurable impact on hippocampal structure and function as assayed via specific hippocampus-related intermediate phenotypes. In addition to overtransmission in schizophrenia, the Ser allele was associated with altered hippocampal structure and function in healthy subjects, including reduced hippocampal gray matter volume and altered engagement of the hippocampus during several cognitive tasks assayed with functional magnetic resonance imaging. These convergent data suggest that allelic variation within DISC1, either at Ser704Cys or haplotypes monitored by it, increases the risk for schizophrenia and that the mechanism of this effect involves structural and functional alterations in the hippocampal formation. PMID:15939883

  8. Phylogenetic, functional, and structural components of variation in bone growth rate of amniotes.

    PubMed

    Cubo, Jorge; Legendre, Pierre; de Ricqlès, Armand; Montes, Laëtitia; de Margerie, Emmanuel; Castanet, Jacques; Desdevises, Yves

    2008-01-01

    The biological features observed in every living organism are the outcome of three sets of factors: historical (inherited by homology), functional (biological adaptation), and structural (properties inherent to the materials with which organs are constructed, and the morphogenetic rules by which they grow). Integrating them should bring satisfactory causal explanations of empirical data. However, little progress has been accomplished in practice toward this goal, because a methodologically efficient tool was lacking. Here we use a new statistical method of variation partitioning to analyze bone growth in amniotes. (1) Historical component. The variation of bone growth rates contains a significant phylogenetic signal, suggesting that the observed patterns are partly the outcome of shared ancestry. (2) Functional causation. High growth rates, although energy costly, may be adaptive (i.e., they may increase survival rates) in taxa showing short growth periods (e.g., birds). In ectothermic amniotes, low resting metabolic rates may limit the maximum possible growth rates. (3) Structural constraint. Whereas soft tissues grow through a multiplicative process, growth of mineralized tissues is accretionary (additive, i.e., mineralization fronts occur only at free surfaces). Bone growth of many amniotes partially circumvents this constraint: it is achieved not only at the external surface of the bone shaft, but also within cavities included in the bone cortex as it grows centrifugally. Our approach contributes to the unification of historicism, functionalism, and structuralism toward a more integrated evolutionary biology. PMID:18315815

  9. Genetic variation and structure of house sparrow populations: is there an island effect?

    PubMed

    Jensen, Henrik; Moe, Rune; Hagen, Ingerid Julie; Holand, Anna Marie; Kekkonen, Jaana; Tufto, Jarle; Saether, Bernt-Erik

    2013-04-01

    Population genetic structure and intrapopulation levels of genetic variation have important implications for population dynamics and evolutionary processes. Habitat fragmentation is one of the major threats to biodiversity. It leads to smaller population sizes and reduced gene flow between populations and will thus also affect genetic structure. We use a natural system of island and mainland populations of house sparrows along the coast of Norway to characterize the different population genetic properties of fragmented populations. We genotyped 636 individuals distributed across 14 populations at 15 microsatellite loci. The level of genetic differentiation was estimated using F-statistics and specially designed Mantel tests were conducted to study the influence of population type (i.e. mainland or island) and geographic distance on the genetic population structure. Furthermore, the effects of population type, population size and latitude on the level of genetic variation within populations were examined. Our results suggest that genetic processes on islands and mainland differed in two important ways. First, the intrapopulation level of genetic variation tended to be lower and the occurrence of population bottlenecks more frequent on islands than the mainland. Second, although the general level of genetic differentiation was low to moderate, it was higher between island populations than between mainland populations. However, differentiation increased in mainland populations somewhat faster with geographical distance. These results suggest that population bottleneck events and genetic drift have been more important in shaping the genetic composition of island populations compared with populations on the mainland. Such knowledge is relevant for a better understanding of evolutionary processes and conservation of threatened populations. PMID:23379682

  10. Enhanced Laboratory Sensitivity to Variation of the Fine-Structure Constant using Highly Charged Ions

    SciTech Connect

    Berengut, J. C.; Dzuba, V. A.; Flambaum, V. V.

    2010-09-17

    We study atomic systems that are in the frequency range of optical atomic clocks and have enhanced sensitivity to potential time variation of the fine-structure constant {alpha}. The high sensitivity is due to coherent contributions from three factors: high nuclear charge Z, high ionization degree, and significant differences in the configuration composition of the states involved. Configuration crossing keeps the frequencies in the optical range despite the large ionization energies. We discuss a few promising examples that have the largest {alpha} sensitivities seen in atomic systems.

  11. Interpopulation Variation in Contour Feather Structure Is Environmentally Determined in Great Tits

    PubMed Central

    Broggi, Juli; Gamero, Anna; Hohtola, Esa; Orell, Markku; Nilsson, Jan-Åke

    2011-01-01

    Background The plumage of birds is important for flying, insulation and social communication. Contour feathers cover most of the avian body and among other functions they provide a critical insulation layer against heat loss. Feather structure and composition are known to vary among individuals, which in turn determines variation in the insulation properties of the feather. However, the extent and the proximate mechanisms underlying this variation remain unexplored. Methodology/Principal Findings We analyzed contour feather structure from two different great tit populations adapted to different winter regimes, one northern population in Oulu (Finland) and one southern population in Lund (Sweden). Great tits from the two populations differed significantly in feather structure. Birds from the northern population had a denser plumage but consisting of shorter feathers with a smaller proportion containing plumulaceous barbs, compared with conspecifics from the southern population. However, differences disappeared when birds originating from the two populations were raised and moulted in identical conditions in a common-garden experiment located in Oulu, under ad libitum nutritional conditions. All birds raised in the aviaries, including adult foster parents moulting in the same captive conditions, developed a similar feather structure. These feathers were different from that of wild birds in Oulu but similar to wild birds in Lund, the latter moulting in more benign conditions than those of Oulu. Conclusions/Significance Wild populations exposed to different conditions develop contour feather differences either due to plastic responses or constraints. Environmental conditions, such as nutrient availability during feather growth play a crucial role in determining such differences in plumage structure among populations. PMID:21949798

  12. Primary Structural Variation in Anaplasma marginale Msp2 Efficiently Generates Immune Escape Variants

    PubMed Central

    Paradiso, Lydia; Broschat, Shira L.; Noh, Susan M.; Palmer, Guy H.

    2015-01-01

    Antigenic variation allows microbial pathogens to evade immune clearance and establish persistent infection. Anaplasma marginale utilizes gene conversion of a repertoire of silent msp2 alleles into a single active expression site to encode unique Msp2 variants. As the genomic complement of msp2 alleles alone is insufficient to generate the number of variants required for persistence, A. marginale uses segmental gene conversion, in which oligonucleotide segments from multiple alleles are recombined into the expression site to generate a novel msp2 mosaic not represented elsewhere in the genome. Whether these segmental changes are sufficient to evade a broad antibody response is unknown. We addressed this question by identifying Msp2 variants that differed in primary structure within the immunogenic hypervariable region microdomains and tested whether they represented true antigenic variants. The minimal primary structural difference between variants was a single amino acid resulting from a codon insertion, and overall, the amino acid identity among paired microdomains ranged from 18 to 92%. Collectively, 89% of the expressed structural variants were also antigenic variants across all biological replicates, independent of a specific host major histocompatibility complex haplotype. Biological relevance is supported by the following: (i) all structural variants were expressed during infection of a natural host, (ii) the structural variation observed in the microdomains corresponded to the mean length of variants generated by segmental gene conversion, and (iii) antigenic variants were identified using a broad antibody response that developed during infection of a natural host. The findings demonstrate that segmental gene conversion efficiently generates Msp2 antigenic variants. PMID:26259814

  13. On the role of thermal backbone fluctuations in myoglobin ligand gate dynamics

    NASA Astrophysics Data System (ADS)

    Krokhotin, Andrey; Niemi, Antti J.; Peng, Xubiao

    2013-05-01

    We construct an energy function that describes the crystallographic structure of sperm whale myoglobin backbone. As a model in our construction, we use the Protein Data Bank entry 1ABS that has been measured at liquid helium temperature. Consequently, the thermal B-factor fluctuations are very small, which is an advantage in our construction. The energy function that we utilize resembles that of the discrete nonlinear Schrödinger equation. Likewise, ours supports topological solitons as local minimum energy configurations. We describe the 1ABS backbone in terms of topological solitons with a precision that deviates from 1ABS by an average root-mean-square distance, which is less than the experimentally observed Debye-Waller B-factor fluctuation distance. We then subject the topological multi-soliton solution to extensive numerical heating and cooling experiments, over a very wide range of temperatures. We concentrate in particular to temperatures above 300 K and below the Θ-point unfolding temperature, which is around 348 K. We confirm that the behavior of the topological multi-soliton is fully consistent with Anfinsen's thermodynamic principle, up to very high temperatures. We observe that the structure responds to an increase of temperature consistently in a very similar manner. This enables us to characterize the onset of thermally induced conformational changes in terms of three distinct backbone ligand gates. One of the gates is made of the helix F and the helix E. The two other gates are chosen similarly, when open they provide a direct access route for a ligand to reach the heme. We find that out of the three gates we investigate, the one which is formed by helices B and G is the most sensitive to thermally induced conformational changes. Our approach provides a novel perspective to the important problem of ligand entry and exit.

  14. Exposing Hidden Alternative Backbone Conformations in X-ray Crystallography Using qFit

    PubMed Central

    Keedy, Daniel A.; Fraser, James S.; van den Bedem, Henry

    2015-01-01

    Proteins must move between different conformations of their native ensemble to perform their functions. Crystal structures obtained from high-resolution X-ray diffraction data reflect this heterogeneity as a spatial and temporal conformational average. Although movement between natively populated alternative conformations can be critical for characterizing molecular mechanisms, it is challenging to identify these conformations within electron density maps. Alternative side chain conformations are generally well separated into distinct rotameric conformations, but alternative backbone conformations can overlap at several atomic positions. Our model building program qFit uses mixed integer quadratic programming (MIQP) to evaluate an extremely large number of combinations of sidechain conformers and backbone fragments to locally explain the electron density. Here, we describe two major modeling enhancements to qFit: peptide flips and alternative glycine conformations. We find that peptide flips fall into four stereotypical clusters and are enriched in glycine residues at the n+1 position. The potential for insights uncovered by new peptide flips and glycine conformations is exemplified by HIV protease, where different inhibitors are associated with peptide flips in the “flap” regions adjacent to the inhibitor binding site. Our results paint a picture of peptide flips as conformational switches, often enabled by glycine flexibility, that result in dramatic local rearrangements. Our results furthermore demonstrate the power of large-scale computational analysis to provide new insights into conformational heterogeneity. Overall, improved modeling of backbone heterogeneity with high-resolution X-ray data will connect dynamics to the structure-function relationship and help drive new design strategies for inhibitors of biomedically important systems. PMID:26506617

  15. Exposing hidden alternative backbone conformations in X-ray crystallography using qFit

    DOE PAGESBeta

    Keedy, Daniel A.; Fraser, James S.; van den Bedem, Henry; Shehu, Amarda

    2015-10-27

    Proteins must move between different conformations of their native ensemble to perform their functions. Crystal structures obtained from high-resolution X-ray diffraction data reflect this heterogeneity as a spatial and temporal conformational average. Although movement between natively populated alternative conformations can be critical for characterizing molecular mechanisms, it is challenging to identify these conformations within electron density maps. Alternative side chain conformations are generally well separated into distinct rotameric conformations, but alternative backbone conformations can overlap at several atomic positions. Our model building program qFit uses mixed integer quadratic programming (MIQP) to evaluate an extremely large number of combinations of sidechainmore » conformers and backbone fragments to locally explain the electron density. Here, we describe two major modeling enhancements to qFit: peptide flips and alternative glycine conformations. We find that peptide flips fall into four stereotypical clusters and are enriched in glycine residues at the n+1 position. The potential for insights uncovered by new peptide flips and glycine conformations is exemplified by HIV protease, where different inhibitors are associated with peptide flips in the “flap” regions adjacent to the inhibitor binding site. Our results paint a picture of peptide flips as conformational switches, often enabled by glycine flexibility, that result in dramatic local rearrangements. Our results furthermore demonstrate the power of large-scale computational analysis to provide new insights into conformational heterogeneity. Furthermore, improved modeling of backbone heterogeneity with high-resolution X-ray data will connect dynamics to the structure-function relationship and help drive new design strategies for inhibitors of biomedically important systems.« less

  16. Exposing hidden alternative backbone conformations in X-ray crystallography using qFit

    SciTech Connect

    Keedy, Daniel A.; Fraser, James S.; van den Bedem, Henry; Shehu, Amarda

    2015-10-27

    Proteins must move between different conformations of their native ensemble to perform their functions. Crystal structures obtained from high-resolution X-ray diffraction data reflect this heterogeneity as a spatial and temporal conformational average. Although movement between natively populated alternative conformations can be critical for characterizing molecular mechanisms, it is challenging to identify these conformations within electron density maps. Alternative side chain conformations are generally well separated into distinct rotameric conformations, but alternative backbone conformations can overlap at several atomic positions. Our model building program qFit uses mixed integer quadratic programming (MIQP) to evaluate an extremely large number of combinations of sidechain conformers and backbone fragments to locally explain the electron density. Here, we describe two major modeling enhancements to qFit: peptide flips and alternative glycine conformations. We find that peptide flips fall into four stereotypical clusters and are enriched in glycine residues at the n+1 position. The potential for insights uncovered by new peptide flips and glycine conformations is exemplified by HIV protease, where different inhibitors are associated with peptide flips in the “flap” regions adjacent to the inhibitor binding site. Our results paint a picture of peptide flips as conformational switches, often enabled by glycine flexibility, that result in dramatic local rearrangements. Our results furthermore demonstrate the power of large-scale computational analysis to provide new insights into conformational heterogeneity. Furthermore, improved modeling of backbone heterogeneity with high-resolution X-ray data will connect dynamics to the structure-function relationship and help drive new design strategies for inhibitors of biomedically important systems.

  17. New limits on variation of the fine-structure constant using atomic dysprosium.

    PubMed

    Leefer, N; Weber, C T M; Cingöz, A; Torgerson, J R; Budker, D

    2013-08-01

    We report on the spectroscopy of radio-frequency transitions between nearly degenerate, opposite-parity excited states in atomic dysprosium (Dy). Theoretical calculations predict that these states are very sensitive to variation of the fine-structure constant α owing to large relativistic corrections of opposite sign for the opposite-parity levels. The near degeneracy reduces the relative precision necessary to place constraints on variation of α, competitive with results obtained from the best atomic clocks in the world. Additionally, the existence of several abundant isotopes of Dy allows isotopic comparisons that suppress common-mode systematic errors. The frequencies of the 754-MHz transition in 164Dy and 235-MHz transition in 162Dy are measured over the span of two years. The linear variation of α is α·/α=(-5.8±6.9([1σ]))×10(-17)  yr(-1), consistent with zero. The same data are used to constrain the dimensionless parameter kα characterizing a possible coupling of α to a changing gravitational potential. We find that kα=(-5.5±5.2([1σ]))×10(-7), essentially consistent with zero and the best constraint to date. PMID:23971546

  18. Genetic population structure and call variation in a passerine bird, the satin bowerbird, Ptilonorhynchus violaceus.

    PubMed

    Nicholls, J A; Austin, J J; Moritz, C; Goldizen, A W

    2006-06-01

    Geographic variation in vocalizations is widespread in passerine birds, but its origins and maintenance remain unclear. One hypothesis to explain this variation is that it is associated with geographic isolation among populations and therefore should follow a vicariant pattern similar to that typically found in neutral genetic markers. Alternatively, if environmental selection strongly influences vocalizations, then genetic divergence and vocal divergence may be disassociated. This study compared genetic divergence derived from 11 microsatellite markers with a metric of phenotypic divergence derived from male bower advertisement calls. Data were obtained from 16 populations throughout the entire distribution of the satin bowerbird, an Australian wet-forest-restricted passerine. There was no relationship between call divergence and genetic divergence, similar to most other studies on birds with learned vocalizations. Genetic divergence followed a vicariant model of evolution, with the differentiation of isolated populations and isolation-by-distance among continuous populations. Previous work on Ptilonorhynchus violaceus has shown that advertisement call structure is strongly influenced by the acoustic environment of different habitats. Divergence in vocalizations among genetically related populations in different habitats indicates that satin bowerbirds match their vocalizations to the environment in which they live, despite the homogenizing influence of gene flow. In combination with convergence of vocalizations among genetically divergent populations occurring in the same habitat, this shows the overriding importance that habitat-related selection can have on the establishment and maintenance of variation in vocalizations. PMID:16892977

  19. Effects of temperature variations on guided waves propagating in composite structures

    NASA Astrophysics Data System (ADS)

    Shoja, Siavash; Berbyuk, Viktor; Boström, Anders

    2016-04-01

    Effects of temperature on guided waves propagating in composite materials is a well-known problem which has been investigated in many studies. The majority of the studies is focused on effects of high temperature. Understanding the effects of low temperature has major importance in composite structures and components which are operating in cold climate conditions such as e.g. wind turbines operating in cold climate regions. In this study first the effects of temperature variations on guided waves propagating in a composite plate is investigated experimentally in a cold climate chamber. The material is a common material used to manufacture rotor blades of wind turbines. The temperature range is 25°C to -25°C and effects of temperature variations on amplitude and phase shift of the received signal are investigated. In order to apply the effects of lowering the temperature on the received signal, the Baseline Signal Stretch (BSS) method is modified and used. The modification is based on decomposing the signal into symmetric and asymmetric modes and applying two different stretch factors on each of them. Finally the results obtained based on the new method is compared with the results of application of BSS with one stretch factor and experimental measurements. Comparisons show that an improvement is obtained using the BSS with the mode decomposition method at temperature variations of more than 25°C.

  20. Updated constraints on spatial variations of the fine-structure constant

    NASA Astrophysics Data System (ADS)

    Pinho, A. M. M.; Martins, C. J. A. P.

    2016-05-01

    Recent work by Webb et al. has provided indications of spatial variations of the fine-structure constant, α, at a level of a few parts per million. Using a dataset of 293 archival measurements, they further show that a dipole provides a statistically good fit to the data, a result subsequently confirmed by other authors. Here we show that a more recent dataset of dedicated measurements further constrains these variations: although there are only 10 such measurements, their uncertainties are considerably smaller. We find that a dipolar variation is still a good fit to the combined dataset, but the amplitude of such a dipole must be somewhat smaller: 8.1 ± 1.7 ppm for the full dataset, versus 9.4 ± 2.2 ppm for the Webb et al. data alone, both at the 68.3% confidence level. Constraints on the direction on the sky of such a dipole are also significantly improved. On the other hand the data can't yet discriminate between a pure spatial dipole and one with an additional redshift dependence.

  1. Backbone and side chain chemical shift assignments of apolipophorin III from Galleria mellonella.

    PubMed

    Crowhurst, Karin A; Horn, James V C; Weers, Paul M M

    2016-04-01

    Apolipophorin III, a 163 residue monomeric protein from the greater wax moth Galleria mellonella (abbreviated as apoLp-IIIGM), has roles in upregulating expression of antimicrobial proteins as well as binding and deforming bacterial membranes. Due to its similarity to vertebrate apolipoproteins there is interest in performing atomic resolution analysis of apoLp-IIIGM as part of an effort to better understand its mechanism of action in innate immunity. In the first step towards structural characterization of apoLp-IIIGM, 99 % of backbone and 88 % of side chain (1)H, (13)C and (15)N chemical shifts were assigned. TALOS+ analysis of the backbone resonances has predicted that the protein is composed of five long helices, which is consistent with the reported structures of apolipophorins from other insect species. The next stage in the characterization of apoLp-III from G. mellonella will be to utilize these resonance assignments in solving the solution structure of this protein. PMID:26493308

  2. Variation in the structural subunit and basal protein antigens of Bacteroides nodosus fimbriae.

    PubMed Central

    Anderson, B J; Kristo, C L; Egerton, J R; Mattick, J S

    1986-01-01

    The fimbriae of Bacteroides nodosus play a major role in protective immunity against ovine footrot and are an important determinant in the serological classification system that divides field isolates into at least eight serogroups and 16 serotypes. Purified fimbriae contain two polypeptide antigens, the structural subunit of the fimbrial strand (molecular weight about 17,000) and a basal protein (molecular weight about 80,000), both of which exhibit structural variation. Fimbriae were prepared from all prototype strains, as well as from a number of other isolates representative of each of the B. nodosus serotypes, and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Substantial variation was observed in the electrophoretic mobility of the fimbrial subunits from the prototypes of each of the eight serogroups. With the exception of serogroup H, which is an unusual case, the apparent molecular weights of the fimbrial subunits ranged from about 16,500 in serogroup D to 19,000 in serogroup F (serotype 1); in serogroup A, B, C and E, the apparent molecular weights were clustered in the range of 17,000 to 17,500, whereas serogroup G was about 18,500. Serogroup H fimbriae appeared to consist of two smaller polypeptides, which in the prototype (H1) had apparent molecular weights of about 6,000 and 10,000 and which seem to have arisen as a consequence of an internal proteolytic nick in the original subunit. Electrophoretic variation in the fimbrial subunit was also observed between different serotypes, although with the exceptions of serogroups F and H, this was not as pronounced as between the serogroups. Examination of a number of isolates classified within the same serotypes showed that some variation, although minor, also occurred at this level. The basal antigen exhibited significant variation at all levels of the serotypic hierarchy in a manner apparently unrelated to the classification system. Among the range of isolates examined, the apparent

  3. Vertical tilt structure of East Asian trough and its interannual variation mechanism in boreal winter

    NASA Astrophysics Data System (ADS)

    Chen, Shangfeng; Chen, Xiaolong; Wei, Ke; Chen, Wen; Zhou, Tianjun

    2014-02-01

    Vertical tilt structure of the East Asian trough (EAT) and its interannual variation mechanism in boreal winter are studied using NCEP/NCAR, ERA40, and NCEP/DOE reanalyses. A vertical tilt index (VTI) is defined as the mean slope of vertical trough line on the longitude-height cross section to describe the tilting extent of the EAT, with high index indicating a more west-tilted trough and vice versa. The VTI series derived from the three reanalysis datasets are highly correlated with each other during the corresponding periods. A significant positive correlation is found between the VTI and the zonal range of the vertical trough line. Based on the close relation, a possible physical mechanism is proposed to explain the interannual variation of VTI. It demonstrates that positive (negative) temperature anomalies within the mean zonal range of the EAT result in expansion (contraction) of the zonal range and lead to high (low) VTI years. The composite analyses based on the three reanalysis datasets well support the proposed mechanism. Furthermore, the general relationship between the VTI and the zonal temperature gradient is discussed based on the proposed mechanism. It is revealed that the asymmetric change of temperature gradient on the western and eastern sides of the EAT plays an important role in the variation of VTI, which suggests that the tilting extent of the EAT is strongly affected by the two-order zonal change of temperature instead of the zonal temperature gradient (i.e., one-order change). Climate variability not only in the simultaneous winter but also in the following spring and summer over East Asia is closely related to the variation of the VTI. This study on the vertical tilting of the EAT may enrich knowledge of the East Asian winter monsoon and the climate variability over East Asia and may be helpful in improving the regional climate prediction in East Asia.

  4. Structural propensities of kinase family proteins from a Potts model of residue co-variation.

    PubMed

    Haldane, Allan; Flynn, William F; He, Peng; Vijayan, R S K; Levy, Ronald M

    2016-08-01

    Understanding the conformational propensities of proteins is key to solving many problems in structural biology and biophysics. The co-variation of pairs of mutations contained in multiple sequence alignments of protein families can be used to build a Potts Hamiltonian model of the sequence patterns which accurately predicts structural contacts. This observation paves the way to develop deeper connections between evolutionary fitness landscapes of entire protein families and the corresponding free energy landscapes which determine the conformational propensities of individual proteins. Using statistical energies determined from the Potts model and an alignment of 2896 PDB structures, we predict the propensity for particular kinase family proteins to assume a "DFG-out" conformation implicated in the susceptibility of some kinases to type-II inhibitors, and validate the predictions by comparison with the observed structural propensities of the corresponding proteins and experimental binding affinity data. We decompose the statistical energies to investigate which interactions contribute the most to the conformational preference for particular sequences and the corresponding proteins. We find that interactions involving the activation loop and the C-helix and HRD motif are primarily responsible for stabilizing the DFG-in state. This work illustrates how structural free energy landscapes and fitness landscapes of proteins can be used in an integrated way, and in the context of kinase family proteins, can potentially impact therapeutic design strategies. PMID:27241634

  5. Robust classification of protein variation using structural modelling and large-scale data integration

    PubMed Central

    Baugh, Evan H.; Simmons-Edler, Riley; Müller, Christian L.; Alford, Rebecca F.; Volfovsky, Natalia; Lash, Alex E.; Bonneau, Richard

    2016-01-01

    Existing methods for interpreting protein variation focus on annotating mutation pathogenicity rather than detailed interpretation of variant deleteriousness and frequently use only sequence-based or structure-based information. We present VIPUR, a computational framework that seamlessly integrates sequence analysis and structural modelling (using the Rosetta protein modelling suite) to identify and interpret deleterious protein variants. To train VIPUR, we collected 9477 protein variants with known effects on protein function from multiple organisms and curated structural models for each variant from crystal structures and homology models. VIPUR can be applied to mutations in any organism's proteome with improved generalized accuracy (AUROC .83) and interpretability (AUPR .87) compared to other methods. We demonstrate that VIPUR's predictions of deleteriousness match the biological phenotypes in ClinVar and provide a clear ranking of prediction confidence. We use VIPUR to interpret known mutations associated with inflammation and diabetes, demonstrating the structural diversity of disrupted functional sites and improved interpretation of mutations associated with human diseases. Lastly, we demonstrate VIPUR's ability to highlight candidate variants associated with human diseases by applying VIPUR to de novo variants associated with autism spectrum disorders. PMID:26926108

  6. Robust classification of protein variation using structural modelling and large-scale data integration.

    PubMed

    Baugh, Evan H; Simmons-Edler, Riley; Müller, Christian L; Alford, Rebecca F; Volfovsky, Natalia; Lash, Alex E; Bonneau, Richard

    2016-04-01

    Existing methods for interpreting protein variation focus on annotating mutation pathogenicity rather than detailed interpretation of variant deleteriousness and frequently use only sequence-based or structure-based information. We present VIPUR, a computational framework that seamlessly integrates sequence analysis and structural modelling (using the Rosetta protein modelling suite) to identify and interpret deleterious protein variants. To train VIPUR, we collected 9477 protein variants with known effects on protein function from multiple organisms and curated structural models for each variant from crystal structures and homology models. VIPUR can be applied to mutations in any organism's proteome with improved generalized accuracy (AUROC .83) and interpretability (AUPR .87) compared to other methods. We demonstrate that VIPUR's predictions of deleteriousness match the biological phenotypes in ClinVar and provide a clear ranking of prediction confidence. We use VIPUR to interpret known mutations associated with inflammation and diabetes, demonstrating the structural diversity of disrupted functional sites and improved interpretation of mutations associated with human diseases. Lastly, we demonstrate VIPUR's ability to highlight candidate variants associated with human diseases by applying VIPUR tode novovariants associated with autism spectrum disorders. PMID:26926108

  7. Structural variation of the feeder dikes of explosive eruptions in Miyakejima, Japan

    NASA Astrophysics Data System (ADS)

    Geshi, Nobuo

    2013-04-01

    Explosive eruptions of basaltic volcanoes exhibit wide variation about its explosivity, from stable lava effusion, mild strombolian eruption, to plinian eruption. Complex behavior of magma within the conduit may control the style of eruption activities, and the structure of the conduit controls the behavior of the ascending magma through the conduit. Existence of external water (ground water) may also affect the explosivity of the eruption. In the caldera wall of Miyakejima, Japan, we can observe various type of the cross section of feeder dikes with its surface products. The new caldera wall exhibits the cross section of a basaltic stratovolcano with numerous feeder and non-feeder dikes. Some feeder dikes connect directly to the lava flow. Some feeder dikes connect to the base of scoria cone with 100- 200 meters across and several tens meters high. Size and internal structure of the scoria cone indicates the mild strombolian activity. Uppermost ten meters of these feeder dikes shows upward-flaring (widen the dike thickness to the surface), which infers the magmatic erosion of the dike wall by explosive activities. More explosive activities formed some diatremes. The depth of these diatreme reaches 100 meters from the original ground surface. Typically, these diatremes connect to very-flat scoria cone and wide-spread thick scoria-fall deposit, which indicates the explosive magmatic activities. The sizes of these flat scoria cones are comparable to that of the scoria cones which was built by sub-plinian eruption (e.g., Izu-Oshima 1986). Upward flaring structure of the diatreme indicates the effective mechanical erosion of the dike wall by the explosive activities. The caldera wall also exhibits some diatremes which formed by the phreatomagmatic eruptions (Suoana diatreme). The wider feeder dikes for lager diatreme suggests the higher magmatic overpressure for the explosive activities in comparison to the less-explosive feeder dikes. Comparison of the structures of

  8. Variational quantum Monte Carlo calculation of electronic and structural properties of crystals

    SciTech Connect

    Louie, S.G.

    1989-09-01

    Calculation of the electronic and structural properties of solids using a variational quantum Monte Carlo nonlocal pseudopotential approach is described. Ionization potentials and electron affinities for atoms, and binding energies and structural properties for crystals are found to be in very good agreement with experiment. The approach employs a correlated many-electron wavefunction of the Jastrow-Slater form and the exact Coulomb interaction between valence electrons. One- and two-body terms in the Jastrow factor are used and found necessary for an accurate description of the electron-electron energy for the systems considered. The method has further been applied to compute various single-particle properties for solids including the single-particle orbital occupancy, electron pair correlation functions, and quasiparticle excitation energies. 23 refs., 3 figs., 3 tabs.

  9. Structural Variation and Uniformity among Tetraloop-Receptor Interactions and Other Loop-Helix Interactions in RNA Crystal Structures

    PubMed Central

    Wu, Li; Chai, Dinggeng; Fraser, Marie E.; Zimmerly, Steven

    2012-01-01

    Tetraloop-receptor interactions are prevalent structural units in RNAs, and include the GAAA/11-nt and GNRA-minor groove interactions. In this study, we have compiled a set of 78 nonredundant loop-helix interactions from X-ray crystal structures, and examined them for the extent of their sequence and structural variation. Of the 78 interactions in the set, only four were classical GAAA/11-nt motifs, while over half (48) were GNRA-minor groove interactions. The GNRA-minor groove interactions were not a homogeneous set, but were divided into five subclasses. The most predominant subclass is characterized by two triple base pair interactions in the minor groove, flanked by two ribose zipper contacts. This geometry may be considered the “standard” GNRA-minor groove interaction, while the other four subclasses are alternative ways to form interfaces between a minor groove and tetraloop. The remaining 26 structures in the set of 78 have loops interacting with mostly idiosyncratic receptors. Among the entire set, a number of sequence-structure correlations can be identified, which may be used as initial hypotheses in predicting three-dimensional structures from primary sequences. Conversely, other sequence patterns are not predictive; for example, GAAA loop sequences and GG/CC receptors bind to each other with three distinct geometries. Finally, we observe an example of structural evolution in group II introns, in which loop-receptor motifs are substituted for each other while maintaining the larger three-dimensional geometry. Overall, the study gives a more complete view of RNA loop-helix interactions that exist in nature. PMID:23152878

  10. Implementation of Speed Variation in the Structural Dynamic Assessment of Turbomachinery Flow-Path Components

    NASA Technical Reports Server (NTRS)

    Brown, Andrew M.; Davis, R. Benjamin; DeHaye, Michael K.

    2013-01-01

    During the design of turbomachinery flow path components, the assessment of possible structural resonant conditions is critical. Higher frequency modes of these structures are frequently found to be subject to resonance, and in these cases, design criteria require a forced response analysis of the structure with the assumption that the excitation speed exactly equals the resonant frequency. The design becomes problematic if the response analysis shows a violation of the HCF criteria. One possible solution is to perform "finite-life" analysis, where Miner's rule is used to calculate the actual life in seconds in comparison to the required life. In this situation, it is beneficial to incorporate the fact that, for a variety of turbomachinery control reasons, the speed of the rotor does not actually dwell at a single value but instead dithers about a nominal mean speed and during the time that the excitation frequency is not equal to the resonant frequency, the damage accumulated by the structure is diminished significantly. Building on previous investigations into this process, we show that a steady-state assumption of the response is extremely accurate for this typical case, resulting in the ability to quickly account for speed variation in the finite-life analysis of a component which has previously had its peak dynamic stress at resonance calculated. A technique using Monte Carlo simulation is also presented which can be used when specific speed time histories are not available. The implementation of these techniques can prove critical for successful turbopump design, as the improvement in life when speed variation is considered is shown to be greater than a factor of two.

  11. Implementation of Speed Variation in the Structural Dynamic Assessment of Turbomachinery Flow-Path Components

    NASA Technical Reports Server (NTRS)

    Brown, Andrew M.; Davis, R. Benjamin; DeHaye, Michael

    2013-01-01

    During the design of turbomachinery flow path components, the assessment of possible structural resonant conditions is critical. Higher frequency modes of these structures are frequently found to be subject to resonance, and in these cases, design criteria require a forced response analysis of the structure with the assumption that the excitation speed exactly equals the resonant frequency. The design becomes problematic if the response analysis shows a violation of the HCF criteria. One possible solution is to perform "finite-life" analysis, where Miner's rule is used to calculate the actual life in seconds in comparison to the required life. In this situation, it is beneficial to incorporate the fact that, for a variety of turbomachinery control reasons, the speed of the rotor does not actually dwell at a single value but instead dithers about a nominal mean speed and during the time that the excitation frequency is not equal to the resonant frequency, the damage accumulated by the structure is diminished significantly. Building on previous investigations into this process, we show that a steady-state assumption of the response is extremely accurate for this typical case, resulting in the ability to quickly account for speed variation in the finite-life analysis of a component which has previously had its peak dynamic stress at resonance calculated. A technique using Monte Carlo simulation is also presented which can be used when specific speed time histories are not available. The implementation of these techniques can prove critical for successful turbopump design, as the improvement in life when speed variation is considered is shown to be greater than a factor of two

  12. Antigenic Variation in Plasmodium falciparum Malaria Involves a Highly Structured Switching Pattern

    PubMed Central

    Recker, Mario; Buckee, Caroline O.; Serazin, Andrew; Kyes, Sue; Pinches, Robert; Christodoulou, Zóe; Springer, Amy L.; Gupta, Sunetra; Newbold, Chris I.

    2011-01-01

    Many pathogenic bacteria, fungi, and protozoa achieve chronic infection through an immune evasion strategy known as antigenic variation. In the human malaria parasite Plasmodium falciparum, this involves transcriptional switching among members of the var gene family, causing parasites with different antigenic and phenotypic characteristics to appear at different times within a population. Here we use a genome-wide approach to explore this process in vitro within a set of cloned parasite populations. Our analyses reveal a non-random, highly structured switch pathway where an initially dominant transcript switches via a set of switch-intermediates either to a new dominant transcript, or back to the original. We show that this specific pathway can arise through an evolutionary conflict in which the pathogen has to optimise between safeguarding its limited antigenic repertoire and remaining capable of establishing infections in non-naïve individuals. Our results thus demonstrate a crucial role for structured switching during the early phases of infections and provide a unifying theory of antigenic variation in P. falciparum malaria as a balanced process of parasite-intrinsic switching and immune-mediated selection. PMID:21408201

  13. Geology, Soils and Basin-wide variations in Amazon Forest Structure and function

    NASA Astrophysics Data System (ADS)

    Quesada, Carlos Alberto; Phillips, Oliver; Lopes-Gonzales, Gabriela; Lloyd, Jon; Rainfor Team

    2015-04-01

    Forest productivity, tree turnover time and above ground biomass vary across the Amazon Basin in an east-west gradient in a pattern which coincides with variations in soil nutrient availability and geology. Forest productivity rates are higher on the most nutrient rich soils close to the Andes while is lower in the ancient, highly weathered soils of central Amazonia. On the other hand above ground biomass is lower in the most productive forests and higher on the least, this being a consequence of higher tree turnover rates in the forests over less weathered and nutrient rich soils. Major geological events have influenced Amazonian soil characteristics profoundly and play an important role in explaining Basin-wide variations in forest biomass, growth and stem turnover rates. Here we show how geology and soil development combine to shape the functioning of Amazonian forests and its carbon stocks and fluxes. To assess the importance of edaphic properties in affect forest structure and dynamics, soil samples were collected in a total of 154 different forest plots across nine different Amazonian countries. Samples were analyzed for exchangeable cations, C, N, pH with various P fractions and soil physical properties also determined. Overall, forest structure and dynamics were found to be strongly and quantitatively related to edaphic conditions.

  14. Variation in the Morphology of Bacillus mycoides Due to Applied Force and Substrate Structure

    PubMed Central

    Stratford, James P.; Woodley, Michael A.; Park, Simon

    2013-01-01

    Response to mechanical force is a well characterised phenomenon in eukaryotic organisms, helping to organise multicellular structures. Mechanotactic responses have only rarely been observed in prokaryotic taxa. This work reports on a morphological change due to variations in applied force and surface structure by Bacillus mycoides Flügge. B. mycoides is a ubiquitous soil organism well known among microbiologists for its characteristic spreading colony morphology. An apparent mechanotactic response is elicited by physical deformation of the gel media on which B.mycoides is growing, including applied forces of compression or tension. Variations in the surface such as curvature produced by casting the agar gel in the presence of curved objects also elicited the change. The morphological change in B.mycoides colonies associated with the application of force manifests as a pattern of parallel rhizoid filaments perpendicular to compressing force and parallel to stretching force in the agar medium. The phenomenon is most clearly demonstrated by reversible changes in the orientation of B. mycoides filaments during time-lapse microscopy. PMID:24324702

  15. SoftSearch: Integration of Multiple Sequence Features to Identify Breakpoints of Structural Variations

    PubMed Central

    Hart, Steven N.; Sarangi, Vivekananda; Moore, Raymond; Baheti, Saurabh; Bhavsar, Jaysheel D.; Couch, Fergus J.; Kocher, Jean-Pierre A.

    2013-01-01

    Background Structural variation (SV) represents a significant, yet poorly understood contribution to an individual’s genetic makeup. Advanced next-generation sequencing technologies are widely used to discover such variations, but there is no single detection tool that is considered a community standard. In an attempt to fulfil this need, we developed an algorithm, SoftSearch, for discovering structural variant breakpoints in Illumina paired-end next-generation sequencing data. SoftSearch combines multiple strategies for detecting SV including split-read, discordant read-pair, and unmated pairs. Co-localized split-reads and discordant read pairs are used to refine the breakpoints. Results We developed and validated SoftSearch using real and synthetic datasets. SoftSearch’s key features are 1) not requiring secondary (or exhaustive primary) alignment, 2) portability into established sequencing workflows, and 3) is applicable to any DNA-sequencing experiment (e.g. whole genome, exome, custom capture, etc.). SoftSearch identifies breakpoints from a small number of soft-clipped bases from split reads and a few discordant read-pairs which on their own would not be sufficient to make an SV call. Conclusions We show that SoftSearch can identify more true SVs by combining multiple sequence features. SoftSearch was able to call clinically relevant SVs in the BRCA2 gene not reported by other tools while offering significantly improved overall performance. PMID:24358278

  16. Membrane Curvature Sensing by Amphipathic Helices Is Modulated by the Surrounding Protein Backbone

    PubMed Central

    Doucet, Christine M.; Esmery, Nina; de Saint-Jean, Maud; Antonny, Bruno

    2015-01-01

    Membrane curvature is involved in numerous biological pathways like vesicle trafficking, endocytosis or nuclear pore complex assembly. In addition to its topological role, membrane curvature is sensed by specific proteins, enabling the coordination of biological processes in space and time. Amongst membrane curvature sensors are the ALPS (Amphipathic Lipid Packing Sensors). ALPS motifs are short peptides with peculiar amphipathic properties. They are found in proteins targeted to distinct curved membranes, mostly in the early secretory pathway. For instance, the ALPS motif of the golgin GMAP210 binds trafficking vesicles, while the ALPS motif of Nup133 targets nuclear pores. It is not clear if, besides curvature sensitivity, ALPS motifs also provide target specificity, or if other domains in the surrounding protein backbone are involved. To elucidate this aspect, we studied the subcellular localization of ALPS motifs outside their natural protein context. The ALPS motifs of GMAP210 or Nup133 were grafted on artificial fluorescent probes. Importantly, ALPS motifs are held in different positions and these contrasting architectures were mimicked by the fluorescent probes. The resulting chimeras recapitulated the original proteins localization, indicating that ALPS motifs are sufficient to specifically localize proteins. Modulating the electrostatic or hydrophobic content of Nup133 ALPS motif modified its avidity for cellular membranes but did not change its organelle targeting properties. In contrast, the structure of the backbone surrounding the helix strongly influenced targeting. In particular, introducing an artificial coiled-coil between ALPS and the fluorescent protein increased membrane curvature sensitivity. This coiled-coil domain also provided membrane curvature sensitivity to the amphipathic helix of Sar1. The degree of curvature sensitivity within the coiled-coil context remains correlated to the natural curvature sensitivity of the helices. This suggests

  17. The effect of chirality and steric hindrance on intrinsic backbone conformational propensities: tools for protein design.

    PubMed

    Childers, Matthew Carter; Towse, Clare-Louise; Daggett, Valerie

    2016-07-01

    The conformational propensities of amino acids are an amalgamation of sequence effects, environmental effects and underlying intrinsic behavior. Many have attempted to investigate neighboring residue effects to aid in our understanding of protein folding and improve structure prediction efforts, especially with respect to difficult to characterize states, such as disordered or unfolded states. Host-guest peptide series are a useful tool in examining the propensities of the amino acids free from the surrounding protein structure. Here, we compare the distributions of the backbone dihedral angles (φ/ψ) of the 20 proteogenic amino acids in two different sequence contexts using the AAXAA and GGXGG host-guest pentapeptide series. We further examine their intrinsic behaviors across three environmental contexts: water at 298 K, water at 498 K, and 8 M urea at 298 K. The GGXGG systems provide the intrinsic amino acid propensities devoid of any conformational context. The alanine residues in the AAXAA series enforce backbone chirality, thereby providing a model of the intrinsic behavior of amino acids in a protein chain. Our results show modest differences in φ/ψ distributions due to the steric constraints of the Ala side chains, the magnitudes of which are dependent on the denaturing conditions. One of the strongest factors modulating φ/ψ distributions was the protonation of titratable side chains, and the largest differences observed were in the amino acid propensities for the rarely sampled αL region. PMID:27284086

  18. Supramolecular Organization of the Repetitive Backbone Unit of the Streptococcus pneumoniae Pilus

    PubMed Central

    Spraggon, Glen; Koesema, Eric; Scarselli, Maria; Malito, Enrico; Biagini, Massimiliano; Norais, Nathalie; Emolo, Carla; Barocchi, Michèle Anne; Giusti, Fabiola; Hilleringmann, Markus; Rappuoli, Rino; Lesley, Scott; Covacci, Antonello; Masignani, Vega; Ferlenghi, Ilaria

    2010-01-01

    Streptococcus pneumoniae, like many other Gram-positive bacteria, assembles long filamentous pili on their surface through which they adhere to host cells. Pneumococcal pili are formed by a backbone, consisting of the repetition of the major component RrgB, and two accessory proteins (RrgA and RrgC). Here we reconstruct by transmission electron microscopy and single particle image reconstruction method the three dimensional arrangement of two neighbouring RrgB molecules, which represent the minimal repetitive structural domain of the native pilus. The crystal structure of the D2-D4 domains of RrgB was solved at 1.6 Å resolution. Rigid-body fitting of the X-ray coordinates into the electron density map enabled us to define the arrangement of the backbone subunits into the S. pneumoniae native pilus. The quantitative fitting provide evidence that the pneumococcal pilus consists uniquely of RrgB monomers assembled in a head-to-tail organization. The presence of short intra-subunit linker regions connecting neighbouring domains provides the molecular basis for the intrinsic pilus flexibility. PMID:20559564

  19. RNA-Redesign: a web server for fixed-backbone 3D design of RNA.

    PubMed

    Yesselman, Joseph D; Das, Rhiju

    2015-07-01

    RNA is rising in importance as a design medium for interrogating fundamental biology and for developing therapeutic and bioengineering applications. While there are several online servers for design of RNA secondary structure, there are no tools available for the rational design of 3D RNA structure. Here we present RNA-Redesign (http://rnaredesign.stanford.edu), an online 3D design tool for RNA. This resource utilizes fixed-backbone design to optimize the sequence identity and nucleobase conformations of an RNA to match a desired backbone, analogous to fundamental tools that underlie rational protein engineering. The resulting sequences suggest thermostabilizing mutations that can be experimentally verified. Further, sequence preferences that differ between natural and computationally designed sequences can suggest whether natural sequences possess functional constraints besides folding stability, such as cofactor binding or conformational switching. Finally, for biochemical studies, the designed sequences can suggest experimental tests of 3D models, including concomitant mutation of base triples. In addition to the designs generated, detailed graphical analysis is presented through an integrated and user-friendly environment. PMID:25964298

  20. NMR Backbone Assignment of Large Proteins by Using (13) Cα -Only Triple-Resonance Experiments.

    PubMed

    Wei, Qingtao; Chen, Jiajing; Mi, Juan; Zhang, Jiahai; Ruan, Ke; Wu, Jihui

    2016-07-01

    Nuclear magnetic resonance (NMR) is a powerful tool to interrogate protein structure and dynamics residue by residue. However, the prerequisite chemical-shift assignment remains a bottleneck for large proteins due to the fast relaxation and the frequency degeneracy of the (13) Cα nuclei. Herein, we present a covariance NMR strategy to assign the backbone chemical shifts by using only HN(CO)CA and HNCA spectra that has a high sensitivity even for large proteins. By using the peak linear correlation coefficient (LCC), which is a sensitive probe even for tiny chemical-shift displacements, we correctly identify the fidelity of approximately 92 % cross-peaks in the covariance spectrum, which is thus a significant improvement on the approach developed by Snyder and Brüschweiler (66 %) and the use of spectral derivatives (50 %). Thus, we calculate the 4D covariance spectrum from HN(CO)CA and HNCA experiments, in which cross-peaks with LCCs above a universal threshold are considered as true correlations. This 4D covariance spectrum enables the sequential assignment of a 42 kDa maltose binding protein (MBP), in which about 95 % residues are successfully assigned with a high accuracy of 98 %. Our LCC approach, therefore, paves the way for a residue-by-residue study of the backbone structure and dynamics of large proteins. PMID:27276173

  1. Colloidal quantum dot lasers built on a passive two-dimensional photonic crystal backbone

    NASA Astrophysics Data System (ADS)

    Chang, Hojun; Min, Kyungtaek; Lee, Myungjae; Kang, Minsu; Park, Yeonsang; Cho, Kyung-Sang; Roh, Young-Geun; Woo Hwang, Sung; Jeon, Heonsu

    2016-03-01

    We report the room-temperature lasing action from two-dimensional photonic crystal (PC) structures composed of a passive Si3N4 backbone with an over-coat of CdSe/CdS/ZnS colloidal quantum dots (CQDs) for optical gain. When optically excited, devices lased in dual PC band-edge modes, with the modal dominance governed by the thickness of the CQD over-layer. The demonstrated laser platform should have an impact on future photonic integrated circuits as the on-chip coupling between active and passive components is readily achievable.We report the room-temperature lasing action from two-dimensional photonic crystal (PC) structures composed of a passive Si3N4 backbone with an over-coat of CdSe/CdS/ZnS colloidal quantum dots (CQDs) for optical gain. When optically excited, devices lased in dual PC band-edge modes, with the modal dominance governed by the thickness of the CQD over-layer. The demonstrated laser platform should have an impact on future photonic integrated circuits as the on-chip coupling between active and passive components is readily achievable. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08544f

  2. RNA-Redesign: a web server for fixed-backbone 3D design of RNA

    PubMed Central

    Yesselman, Joseph D.; Das, Rhiju

    2015-01-01

    RNA is rising in importance as a design medium for interrogating fundamental biology and for developing therapeutic and bioengineering applications. While there are several online servers for design of RNA secondary structure, there are no tools available for the rational design of 3D RNA structure. Here we present RNA-Redesign (http://rnaredesign.stanford.edu), an online 3D design tool for RNA. This resource utilizes fixed-backbone design to optimize the sequence identity and nucleobase conformations of an RNA to match a desired backbone, analogous to fundamental tools that underlie rational protein engineering. The resulting sequences suggest thermostabilizing mutations that can be experimentally verified. Further, sequence preferences that differ between natural and computationally designed sequences can suggest whether natural sequences possess functional constraints besides folding stability, such as cofactor binding or conformational switching. Finally, for biochemical studies, the designed sequences can suggest experimental tests of 3D models, including concomitant mutation of base triples. In addition to the designs generated, detailed graphical analysis is presented through an integrated and user-friendly environment. PMID:25964298

  3. A Genome Wide Survey of SNP Variation Reveals the Genetic Structure of Sheep Breeds

    PubMed Central

    Kijas, James W.; Townley, David; Dalrymple, Brian P.; Heaton, Michael P.; Maddox, Jillian F.; McGrath, Annette; Wilson, Peter; Ingersoll, Roxann G.; McCulloch, Russell; McWilliam, Sean; Tang, Dave; McEwan, John; Cockett, Noelle; Oddy, V. Hutton; Nicholas, Frank W.; Raadsma, Herman

    2009-01-01

    The genetic structure of sheep reflects their domestication and subsequent formation into discrete breeds. Understanding genetic structure is essential for achieving genetic improvement through genome-wide association studies, genomic selection and the dissection of quantitative traits. After identifying the first genome-wide set of SNP for sheep, we report on levels of genetic variability both within and between a diverse sample of ovine populations. Then, using cluster analysis and the partitioning of genetic variation, we demonstrate sheep are characterised by weak phylogeographic structure, overlapping genetic similarity and generally low differentiation which is consistent with their short evolutionary history. The degree of population substructure was, however, sufficient to cluster individuals based on geographic origin and known breed history. Specifically, African and Asian populations clustered separately from breeds of European origin sampled from Australia, New Zealand, Europe and North America. Furthermore, we demonstrate the presence of stratification within some, but not all, ovine breeds. The results emphasize that careful documentation of genetic structure will be an essential prerequisite when mapping the genetic basis of complex traits. Furthermore, the identification of a subset of SNP able to assign individuals into broad groupings demonstrates even a small panel of markers may be suitable for applications such as traceability. PMID:19270757

  4. UNCOVERING THE ORIGINS OF SPIRAL STRUCTURE BY MEASURING RADIAL VARIATION IN PATTERN SPEEDS

    SciTech Connect

    Meidt, Sharon E.; Rand, Richard J.; Merrifield, Michael R.

    2009-09-01

    Current theories of spiral and bar structure predict a variety of pattern speed behaviors, calling for detailed, direct measurement of the radial variation of pattern speeds. Our recently developed Radial Tremaine-Weinberg (TWR) method allows this goal to be achieved for the first time. Here, we present TWR spiral pattern speed estimates for M101, IC 342, NGC 3938, and NGC 3344 in order to investigate whether spiral structure is steady or winding, whether spirals are described by multiple pattern speeds, and the relation between bar and spiral speeds. Where possible, we interpret our pattern speeds estimates according to the resonance radii associated with each (established with the disk angular rotation), and compare these to previous determinations. By analyzing the high-quality H I and CO data cubes available for these galaxies, we show that it is possible to determine directly multiple pattern speeds within these systems, and hence identify the characteristic signatures of the processes that drive the spiral structure. Even this small sample of galaxies reveals a surprisingly complex taxonomy, with the first direct evidence for the presence of resonant coupling of multiple patterns found in some systems, and the measurement of a simple single-pattern speed in others. Overall, this study demonstrates that we are now in a position to uncover more of the apparently complex physics that lies behind spiral structure.

  5. Pressure-induced variation of structural, elastic, vibrational, electronic, thermodynamic properties and hardness of Ruthenium Carbides

    NASA Astrophysics Data System (ADS)

    Gopalakrishna Pillai, Harikrishnan; Kulangara Madam, Ajith; Natarajan, Sathish; Chandra, Sharat; Mundachali Cheruvalath, Valsakumar

    2016-07-01

    Three of the five structures obtained from the evolutionary algorithm based structure search of Ruthenium Carbide systems in the stoichiometries RuC, Ru2C and Ru3C are relaxed at different pressures in the range 0-200 GPa and the pressure-induced variation of their structural, elastic, dynamical, electronic and thermodynamic properties as well as hardness is investigated in detail. No structural transition is present for these systems in this pressure range. RuC-Zinc blende is mechanically and dynamically unstable close to 100 GPa. RuC-Rhombohedral and Ru3C-Hexagonal retain mechanical and dynamical stability up to 200 GPa. For all three systems the electronic bands and density of states spread out with pressure and the band gap increases with pressure for the semiconducting RuC-Zinc blende. From the computed IR spectrum of RuC-Zinc blende at 50 GPa it is noted that the IR frequency increases with pressure. Using a semi-empirical model for hardness it is estimated that hardness of all three systems consistently increases with pressure. The hardness of RuC-Zinc blende increases towards the superhard regime up to the limiting pressure of its mechanical stability while that of RuC-Rhombohedral becomes 30 GPa at the pressure of 150 GPa.

  6. Using evolutionary sequence variation to make inferences about protein structure and function

    NASA Astrophysics Data System (ADS)

    Colwell, Lucy

    2015-03-01

    The evolutionary trajectory of a protein through sequence space is constrained by its function. Collections of sequence homologs record the outcomes of millions of evolutionary experiments in which the protein evolves according to these constraints. The explosive growth in the number of available protein sequences raises the possibility of using the natural variation present in homologous protein sequences to infer these constraints and thus identify residues that control different protein phenotypes. Because in many cases phenotypic changes are controlled by more than one amino acid, the mutations that separate one phenotype from another may not be independent, requiring us to understand the correlation structure of the data. To address this we build a maximum entropy probability model for the protein sequence. The parameters of the inferred model are constrained by the statistics of a large sequence alignment. Pairs of sequence positions with the strongest interactions accurately predict contacts in protein tertiary structure, enabling all atom structural models to be constructed. We describe development of a theoretical inference framework that enables the relationship between the amount of available input data and the reliability of structural predictions to be better understood.

  7. Robust identification of backbone curves using control-based continuation

    NASA Astrophysics Data System (ADS)

    Renson, L.; Gonzalez-Buelga, A.; Barton, D. A. W.; Neild, S. A.

    2016-04-01

    Control-based continuation is a recently developed approach for testing nonlinear dynamic systems in a controlled manner and exploring their dynamic features as system parameters are varied. In this paper, control-based continuation is adapted to follow the locus where system response and excitation are in quadrature, extracting the backbone curve of the underlying conservative system. The method is applied to a single-degree-of-freedom oscillator under base excitation, and the results are compared with the standard resonant-decay method.

  8. Scientific Laser Market Still The Backbone Of The Industry

    NASA Astrophysics Data System (ADS)

    Tomkins, Jon

    1988-06-01

    Good morning. I would like to thank Gary Forrest and Laser Focus for giving me the opportunity to participate in this seminar. After listening to Moe Levitt's overview of the industry outlook for 1988, it is a pleasure for me to represent one of the 'hot' sectors in the market - the old research market. My mission today is to provide a perspective of this market to you as one of the healthier parts of the industry, as one of the backbones of our industry.

  9. Contribution of regulatory and structural variations in APOE to predicting dyslipidemia

    PubMed Central

    Stengård, Jari H.; Kardia, Sharon L. R.; Hamon, Sara C.; Frikke-Schmidt, Ruth; Tybjærg-Hansen, Anne; Salomaa, Veikko; Boerwinkle, Eric; Sing, Charles F.

    2006-01-01

    The objective of this study was to evaluate 1) whether non-coding single nucleotide polymorphisms (non-cSNP) in the apolipoprotein E gene (APOE) identified by resequencing studies contribute to statistically explaining dyslipidemia if variations in the two cSNPs in exon 4 that define the ɛ2, ɛ3, and ɛ4 alleles are ignored, and 2) whether the contribution of these additional SNPs persists when variations in the cSNPs are considered. We used an ecological, multiple-population, data-mining strategy to identify single-SNP and two-SNP genotypes that distinguish between high and low levels of plasma lipids in three training samples, European-Americans from Rochester, MN, African-Americans from Jackson, MS, and Europeans from North Karelia, Finland. We found that a pair of SNPs located in the 5' region define genotypes A560T832/A560T832, A560T832/A560G832, and A560T832/T560T832, which distinguish between high and low levels of HDL-cholesterol (HDL-C), triglycerides (TG), and/or total cholesterol (T-C). The A560T832/- genotypes predicted high TG and high T-C in both genders in a large independent test sample from Copenhagen, Denmark. Prediction of high T-C in the Danish females was dependent on genotypes defined by the cSNPs. Our study suggests that both regulatory and structural variations should be considered when evaluating the utility of APOE for predicting dyslipidemia in the population at large. PMID:16317171

  10. Genetic variation of southern hemisphere fur seals (Arctocephalus spp.): investigation of population structure and species identity.

    PubMed

    Lento, G M; Haddon, M; Chambers, G K; Baker, C S

    1997-01-01

    We have examined phylogenetic and geographic patterns of variation in the mitochondrial cytochrome b gene of Southern Hemisphere fur seals (Arctocephalus spp.). Our survey of 106 individuals from four putative species reveals three distinct patterns of variation reflecting ancient, recent historic, and contemporary gene flow. For the combined samples of Subantarctic (Arctocephalus tropicalis) and Antarctic (Arctocephalus gazella) fur seals, we find low levels of sequence diversity and reciprocal paraphyly of hapiotypes (where representative haplotypes of a species are found to occur infrequently in another species and vice versa). For the Australian and Cape fur seal subspecies (Arctocephalus pusillus doriferus and A. p. pusillus, respectively), we find low levels of sequence diversity but significant differences in the regional distribution of haplotypes that are consistent with, but not conclusive of, the current subspecies definition based on nonmolecular data. For the New Zealand fur seal (Arctocephalus forsteri), we find high levels of average sequence diversity because of the survival of two divergent lineages of mitochondrial hapiotypes with differences approaching that found in interspecific comparisons of other mammals. The two divergent clades are distributed sympatrically in some regions, but the overall geographic structure of the variation is significant across the range of this species. These new molecular data are inconsistent with current taxonomic definitions of species within the Southern Hemisphere fur seals and argue for reevaluation of these "species" definitions. For management purposes, the definition of evolutionarily significant units (Ryder 1986) and genetic management units (Moritz 1994) in relation to these species may also be evaluated in light of this molecular genetic information. PMID:9183848

  11. Structural heterogeneity of milk casein micelles: a SANS contrast variation study.

    PubMed

    Bouchoux, Antoine; Ventureira, Jorge; Gésan-Guiziou, Geneviève; Garnier-Lambrouin, Fabienne; Qu, Peng; Pasquier, Coralie; Pézennec, Stéphane; Schweins, Ralf; Cabane, Bernard

    2015-01-14

    We examine the internal structure of milk casein micelles using the contrast variation method in Small-Angle Neutron Scattering (SANS). Experiments were performed with casein dispersions of different origins (i.e., milk powder or fresh milk) and extended to very low q-values (∼9 × 10(-4) Å(-1)), thus making it possible to precisely determine the apparent gyration radius Rg at each contrast. From the variation of I(q → 0) with contrast, we determine the distribution of composition of all the particles in the dispersions. As expected, most of these particles are micelles, made of casein and calcium phosphate, with a narrow distribution in compositions. These micelles always coexist with a very small fraction of fat droplets, with sizes in the range of 20-400 nm. For the dispersions prepared from fresh milk, which were purified under particularly stringent conditions, the number ratio of fat droplets to casein micelles is as low as 1 to 10(6). In that case, we are able to subtract from the total intensity the contribution of the fat droplets and in this way obtain the contribution of the micelles only. We then analyze the variation of this contribution with contrast using the approach pioneered by H. B. Stuhrmann. We model the casein micelle as a core-shell spherical object, in which the local scattering length density is determined by the ratio of calcium phosphate nanoclusters to proteins. We find that models in which the shell has a lower concentration of calcium phosphate than the core give a better agreement than models in which the shell has a higher density than the core. PMID:25388767

  12. Triazine‐Based Sequence‐Defined Polymers with Side‐Chain Diversity and Backbone–Backbone Interaction Motifs

    PubMed Central

    Mo, Kai‐For; Daily, Michael D.

    2016-01-01

    Abstract Sequence control in polymers, well‐known in nature, encodes structure and functionality. Here we introduce a new architecture, based on the nucleophilic aromatic substitution chemistry of cyanuric chloride, that creates a new class of sequence‐defined polymers dubbed TZPs. Proof of concept is demonstrated with two synthesized hexamers, having neutral and ionizable side chains. Molecular dynamics simulations show backbone–backbone interactions, including H‐bonding motifs and pi–pi interactions. This architecture is arguably biomimetic while differing from sequence‐defined polymers having peptide bonds. The synthetic methodology supports the structural diversity of side chains known in peptides, as well as backbone–backbone hydrogen‐bonding motifs, and will thus enable new macromolecules and materials with useful functions. PMID:26865312

  13. Sulfation and Cation Effects on the Conformational Properties of the Glycan Backbone of Chondroitin Sulfate Disaccharides

    PubMed Central

    Faller, Christina E.; Guvench, Olgun

    2015-01-01

    Chondroitin sulfate (CS) is one of several glycosaminoglycans that are major components of proteoglycans. A linear polymer consisting of repeats of the disaccharide -4GlcAβ1-3GalNAcβ1-, CS undergoes differential sulfation resulting in five unique sulfation patterns. Because of the dimer repeat, the CS glycosidic “backbone” has two distinct sets of conformational degrees of freedom defined by pairs of dihedral angles: (ϕ1, ψ1) about the β1-3 glycosidic linkage and (ϕ2, ψ2) about the β1-4 glycosidic linkage. Differential sulfation and the possibility of cation binding, combined with the conformational flexibility and biological diversity of CS, complicate experimental efforts to understand CS three-dimensional structures at atomic resolution. Therefore, all-atom explicit-solvent molecular dynamics simulations with Adaptive Biasing Force sampling of the CS backbone were applied to obtain high resolution, high precision free energies of CS disaccharides as a function of all possible backbone geometries. All ten disaccharides (β1-3 vs. β1-4 linkage x five different sulfation patterns) were studied; additionally, ion effects were investigated by considering each disaccharide in the presence of either neutralizing sodium or calcium cations. GlcAβ1-3GalNAc disaccharides have a single, broad, thermodynamically important free-energy minimum whereas GalNAcβ1-4GlcA disaccharides have two such minima. Calcium cations but not sodium cations bind to the disaccharides, and binding is primarily to the GlcA –COO− moiety as opposed to sulfate groups. This binding alters the glycan backbone thermodynamics in instances where a calcium cation bound to –COO− can act to bridge and stabilize an interaction with an adjacent sulfate group, whereas, in the absence of this cation, the proximity of a sulfate group to –COO− results in two like charges being both desolvated and placed adjacent to each other and is found to be destabilizing. In addition to providing

  14. Implication of Spatial and Temporal Variations of the Fine-Structure Constant

    NASA Astrophysics Data System (ADS)

    Feng, Sze-Shiang; Yan, Mu-Lin

    2016-02-01

    Temporal and spatial variations of fine-structure constant α ≡ e2/hbar c in cosmology have been reported in analysis of combination Keck and VLT data. This paper studies the variations based on consideration of basic spacetime symmetry in physics. Both laboratory α 0 and distant α z are deduced from relativistic spectrum equations of atoms (e.g., hydrogen atom) defined in inertial reference systems. When Einstein's Λ≠0, the metric of local inertial reference systems in SM of cosmology is Beltrami metric instead of Minkowski, and the basic spacetime symmetry has to be de Sitter (dS) group. The corresponding special relativity (SR) is dS-SR. A model based on dS-SR is suggested. Comparing the predictions on α-varying with the data, the parameters are determined. The best-fit dipole mode in α's spatial varying is reproduced by this dS-SR model. α-varyings in whole sky are also studied. The results are generally in agreement with the estimations of observations. The main conclusion is that the phenomenon of α-varying cosmologically with dipole mode dominating is due to the de Sitter (or anti de Sitter) spacetime symmetry with a Minkowski point in an extended special relativity called de Sitter invariant special relativity (dS-SR) developed by Dirac-Inönü-Wigner-Gürsey-Lee-Lu-Zou-Guo.

  15. Spectrophotometry of zonal cloud structure variations on Jupiter, 1988-1993

    NASA Astrophysics Data System (ADS)

    Tejfel, V. G.; Vdovichenko, V. D.; Sinyaeva, N. V.; Mosina, S. A.; Gajsina, W. N.; Kharitonova, G. A.; Aksenov, A. N.

    1994-04-01

    Global changes of zonal cloud structure on Jupiter have been observed and analyzed from data obtained with a 1-m telescope and a low-dispersion spectrograph in the spectral range wavelengths 400-680 nm, and with a 70-cm telescope and planetary three-channel spectrometer in the spectral range wavelengths 320-1100 nm during each Jovian apparition from 1988 to 1992. Variations of the observed meridional intensity profiles and relative spectrophotometric gradients are described as well as the changes of absolute spectral reflectivity of five main belts on Jupiter (North and South Equatorial belts, North and South Tropical zones, and Equatorial region). Some peculiarities in the behavior of spectrophotometric gradients may be interpreted as a result of increased Rayleigh scattering in the gas layer over the deeper effective cloud boundary within main dark belts. The polar limb darkening varies only slightly with wavelength and it may be considered as evidence for dark aerosols in the stratosphere at high latitudes. The intensity of the methane absorption band centered at 8860 A shows an increase from the equator to temperate latitudes throughout the 1988-1992 period, despite the large variations in belt and zone reflectivities observed during this period in the southern hemisphere.

  16. A preliminary investigation into the genetic variation and population structure of Taenia hydatigena from Sardinia, Italy.

    PubMed

    Boufana, Belgees; Scala, Antonio; Lahmar, Samia; Pointing, Steve; Craig, Philip S; Dessì, Giorgia; Zidda, Antonella; Pipia, Anna Paola; Varcasia, Antonio

    2015-11-30

    Cysticercosis caused by the metacestode stage of Taenia hydatigena is endemic in Sardinia. Information on the genetic variation of this parasite is important for epidemiological studies and implementation of control programs. Using two mitochondrial genes, the cytochrome c oxidase subunit 1 (cox1) and the NADH dehydrogenase subunit 1 (ND1) we investigated the genetic variation and population structure of Cysticercus tenuicollis from Sardinian intermediate hosts and compared it to that from other hosts from various geographical regions. The parsimony cox1 network analysis indicated the existence of a common lineage for T. hydatigena and the overall diversity and neutrality indices indicated demographic expansion. Using the cox1 sequences, low pairwise fixation index (Fst) values were recorded for Sardinian, Iranian and Palestinian sheep C. tenuicollis which suggested the absence of genetic differentiation. Using the ND1 sequences, C. tenuicollis from Sardinian sheep appeared to be differentiated from those of goat and pig origin. In addition, goat C. tenuicollis were genetically different from adult T. hydatigena as indicated by the statistically significant Fst value. Our results are consistent with biochemical and morphological studies that suggest the existence of variants of T. hydatigena. PMID:26296591

  17. Multimodal Image Reconstruction Using Supplementary Structural Information in Total Variation Regularization

    NASA Astrophysics Data System (ADS)

    Kazantsev, Daniil; Lionheart, William R. B.; Withers, Philip J.; Lee, Peter D.

    2014-11-01

    In this paper, we propose an iterative reconstruction algorithm which uses available information from one dataset collected using one modality to increase the resolution and signal-to-noise ratio of one collected by another modality. The method operates on the structural information only which increases its suitability across various applications. Consequently, the main aim of this method is to exploit available supplementary data within the regularization framework. The source of primary and supplementary datasets can be acquired using complementary imaging modes where different types of information are obtained (e.g. in medical imaging: anatomical and functional). It is shown by extracting structural information from the supplementary image (direction of level sets) one can enhance the resolution of the other image. Notably, the method enhances edges that are common to both images while not suppressing features that show high contrast in the primary image alone. In our iterative algorithm we use available structural information within a modified total variation penalty term. We provide numerical experiments to show the advantages and feasibility of the proposed technique in comparison to other methods.

  18. Population genetic structure of Pacific white shrimp (Litopenaeus vannamei) from Mexico to Panama: microsatellite DNA variation.

    PubMed

    Valles-Jimenez, R; Cruz, P; Perez-Enriquez, R

    2004-01-01

    Genetic variation and population structure of wild white shrimp (Litopenaeus vannamei) from 4 geographic locations from Mexico to Panama were investigated using 5 microsatellite DNA loci. The genetic diversity between populations was indicated by the mean number of alleles per locus and mean observed heterozygosity, which ranged from 7.4 to 8.6 and from 0.241 to 0.388, respectively. Significant departures from Hardy-Weinberg equilibrium were found at most locations at each locus, with the exception Guatemala at Pvan0013, and were caused by high heterozygote deficiencies. Genetic differences between localities were detected by pairwise comparison based on allelic and genotypic frequencies, with the exception of locus Pvan1003. Significant pairwise F (ST) values between locations and total F (ST) showed that the white shrimp population is structured into subpopulations. However, population differentiation does not follow an isolation-by-distance model. Knowledge of the genetic diversity and structure of L.vannamei populations will be of interest for aquaculture and fisheries management to utilize and preserve aquatic biodiversity. PMID:15791491

  19. Multimodal Image Reconstruction Using Supplementary Structural Information in Total Variation Regularization.

    PubMed

    Kazantsev, Daniil; Lionheart, William R B; Withers, Philip J; Lee, Peter D

    2014-01-01

    In this paper, we propose an iterative reconstruction algorithm which uses available information from one dataset collected using one modality to increase the resolution and signal-to-noise ratio of one collected by another modality. The method operates on the structural information only which increases its suitability across various applications. Consequently, the main aim of this method is to exploit available supplementary data within the regularization framework. The source of primary and supplementary datasets can be acquired using complementary imaging modes where different types of information are obtained (e.g. in medical imaging: anatomical and functional). It is shown by extracting structural information from the supplementary image (direction of level sets) one can enhance the resolution of the other image. Notably, the method enhances edges that are common to both images while not suppressing features that show high contrast in the primary image alone. In our iterative algorithm we use available structural information within a modified total variation penalty term. We provide numerical experiments to show the advantages and feasibility of the proposed technique in comparison to other methods. PMID:25484635

  20. Variations in Crystalline Structures and Electrical Properties of Single Crystalline Boron Nitride Nanosheets

    PubMed Central

    Aldalbahi, Ali; Zhou, Andrew Feng; Feng, Peter

    2015-01-01

    We report the studies of (1) the basic mechanism underlying the formation of defect-free, single crystalline boron nitride nanosheets (BNNSs) synthesized using pulsed laser plasma deposition (PLPD) technique, (2) the variation in the crystalline structure at the edges of the hexagonal boron nitride (h-BN) nanosheets, and (3) the basic electrical properties related to the BNNSs tunneling effect and electrical breakdown voltage. The nanoscale morphologies of BNNSs are characterized using scanning electron microscope (SEM) and high-resolution transmission electron microscope (HRTEM). The results show that each sample consisted of a number of transparent BNNSs that partially overlapped one another. Varying the deposition duration yielded different thicknesses of sample but did not affect the morphology, structure, and thickness of individual BNNSs pieces. Analysis of the SEM and HRTEM data revealed changes in the spatial period of the B3–N3 hexagonal structures and the interlayer distance at the edge of the BNNSs, which occurred due to the limited number of atomic layers and was confirmed further by x-ray diffraction (XRD) study. The experimental results clearly indicate that the values of the electrical conductivities of the super-thin BNNSs and the effect of temperature relied strongly on the direction of observation. PMID:26563901

  1. Variations in Crystalline Structures and Electrical Properties of Single Crystalline Boron Nitride Nanosheets.

    PubMed

    Aldalbahi, Ali; Zhou, Andrew Feng; Feng, Peter

    2015-01-01

    We report the studies of (1) the basic mechanism underlying the formation of defect-free, single crystalline boron nitride nanosheets (BNNSs) synthesized using pulsed laser plasma deposition (PLPD) technique, (2) the variation in the crystalline structure at the edges of the hexagonal boron nitride (h-BN) nanosheets, and (3) the basic electrical properties related to the BNNSs tunneling effect and electrical breakdown voltage. The nanoscale morphologies of BNNSs are characterized using scanning electron microscope (SEM) and high-resolution transmission electron microscope (HRTEM). The results show that each sample consisted of a number of transparent BNNSs that partially overlapped one another. Varying the deposition duration yielded different thicknesses of sample but did not affect the morphology, structure, and thickness of individual BNNSs pieces. Analysis of the SEM and HRTEM data revealed changes in the spatial period of the B3-N3 hexagonal structures and the interlayer distance at the edge of the BNNSs, which occurred due to the limited number of atomic layers and was confirmed further by x-ray diffraction (XRD) study. The experimental results clearly indicate that the values of the electrical conductivities of the super-thin BNNSs and the effect of temperature relied strongly on the direction of observation. PMID:26563901

  2. Geographic variation and genetic structure in the Bahama Oriole (Icterus northropi), a critically endangered synanthropic species

    PubMed Central

    Person, Carl; Hayes, William K.

    2015-01-01

    Bird species may exhibit unexpected population structuring over small distances, with gene flow restricted by geographic features such as water or mountains. The Bahama Oriole (Icterus northropi) is a critically endangered, synanthropic island endemic with a declining population of fewer than 300 individuals. It now remains only on Andros Island (The Bahamas), which is riddled with waterways that past studies assumed did not hinder gene flow. We examined 1,858 base pairs of mitochondrial DNA sequenced from four gene regions in 14 birds (roughly 5% of the remaining population) found on the largest land masses of Andros Island (North Andros and Mangrove Cay/South Andros). We sought to discern genetic structuring between the remaining subpopulations and its relationship to current conservation concerns. Four unique haplotypes were identified, with only one shared between the two subpopulations. Nucleotide and haplotype diversity were higher for the North Andros subpopulation than for the Mangrove Cay/South Andros subpopulation. Analysis of molecular variance (AMOVA) yielded a Wright’s fixation index (Fst) of 0.60 (PFst = 0.016), with 40.2% of the molecular variation explained by within-population differences and 59.8% by among-population differences. Based on the mitochondrial regions examined in this study, we suggest the extant subpopulations of Bahama Oriole exhibit significant population structuring over short distances, consistent with some other non-migratory tropical songbird species. PMID:26644974

  3. The genetic structure of the Kuwaiti population: mtDNA Inter- and intra-population variation.

    PubMed

    Theyab, Jasem B; Al-Bustan, Suzanne; Crawford, Michael H

    2012-08-01

    This study investigated: (1) the mitochondrial DNA (mtDNA) genetic variation in 116 unrelated individuals who originated from the Arabian Peninsula, Iran, or were of Bedouin ethnicity and (2) the genetic structure of Kuwaiti populations and compared it to their neighboring populations. These subpopulations were tested for genetic homogeneity and shown to be heterogeneous. Restriction fragment length polymorphism (RFLP) and mtDNA sequencing analyses of HVRI were used to reconstruct the genetic structure of Kuwait. The results indicated that the combined Kuwaiti population has a high frequency of haplogroup R0 (17%), J (12%), and U (12%) similar to other Arabian populations. In addition, contemporary African gene flow was detected through the presence of sub-haplogroup L (L1 and L2) (2%) and the absence of L3 which is reflective of an earlier migration. Furthermore, the multidimensional scaling (MDS) plot showed that the Kuwaiti population clusters with neighboring populations, including Iran and Saudi Arabia indicating gene flow into Kuwait. According to this study, the Kuwaiti population may be undergoing an expansion in a relatively short period of time, and the maternal genetic structure of Kuwait resembles both Saudi Arabia and Iran. PMID:23249314

  4. Slope variation and population structure of tree species from different ecological groups in South Brazil.

    PubMed

    Bianchini, Edmilson; Garcia, Cristina C; Pimenta, José A; Torezan, José M D

    2010-09-01

    Size structure and spatial arrangement of 13 abundant tree species were determined in a riparian forest fragment in Paraná State, South Brazil (23°16'S and 51°01'W). The studied species were Aspidosperma polyneuron Müll. Arg., Astronium graveolens Jacq. and Gallesia integrifolia (Spreng) Harms (emergent species); Alseis floribunda Schott, Ruprechtia laxiflora Meisn. and Bougainvillea spectabilis Willd. (shade-intolerant canopy species); Machaerium paraguariense Hassl, Myroxylum peruiferum L. and Chrysophyllum gonocarpum (Mart. & Eichler ex Miq.) Engl. (shade-tolerant canopy species); Sorocea bonplandii (Baill.) Bürger, Trichilia casaretti C. Dc, Trichilia catigua A. Juss. and Actinostemon concolor (Spreng.) Müll. Arg. (understory small trees species). Height and diameter structures and basal area of species were analyzed. Spatial patterns and slope correlation were analyzed by Moran's / spatial autocorrelation coefficient and partial Mantel test, respectively. The emergent and small understory species showed the highest and the lowest variations in height, diameter and basal area. Size distribution differed among emergent species and also among canopy shade-intolerant species. The spatial pattern ranged among species in all groups, except in understory small tree species. The slope was correlated with spatial pattern for A. polyneuron, A. graveolens, A. floribunda, R. laxiflora, M. peruiferum and T. casaretti. The results indicated that most species occurred in specific places, suggesting that niche differentiation can be an important factor in structuring the tree community. PMID:21562693

  5. Probabilistic models of genetic variation in structured populations applied to global human studies

    PubMed Central

    Hao, Wei; Song, Minsun; Storey, John D.

    2016-01-01

    Motivation: Modern population genetics studies typically involve genome-wide genotyping of individuals from a diverse network of ancestries. An important problem is how to formulate and estimate probabilistic models of observed genotypes that account for complex population structure. The most prominent work on this problem has focused on estimating a model of admixture proportions of ancestral populations for each individual. Here, we instead focus on modeling variation of the genotypes without requiring a higher-level admixture interpretation. Results: We formulate two general probabilistic models, and we propose computationally efficient algorithms to estimate them. First, we show how principal component analysis can be utilized to estimate a general model that includes the well-known Pritchard–Stephens–Donnelly admixture model as a special case. Noting some drawbacks of this approach, we introduce a new ‘logistic factor analysis’ framework that seeks to directly model the logit transformation of probabilities underlying observed genotypes in terms of latent variables that capture population structure. We demonstrate these advances on data from the Human Genome Diversity Panel and 1000 Genomes Project, where we are able to identify SNPs that are highly differentiated with respect to structure while making minimal modeling assumptions. Availability and Implementation: A Bioconductor R package called lfa is available at http://www.bioconductor.org/packages/release/bioc/html/lfa.html. Contact: jstorey@princeton.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26545820

  6. Geographic variation and genetic structure in the Bahama Oriole (Icterus northropi), a critically endangered synanthropic species.

    PubMed

    Price, Melissa R; Person, Carl; Hayes, William K

    2015-01-01

    Bird species may exhibit unexpected population structuring over small distances, with gene flow restricted by geographic features such as water or mountains. The Bahama Oriole (Icterus northropi) is a critically endangered, synanthropic island endemic with a declining population of fewer than 300 individuals. It now remains only on Andros Island (The Bahamas), which is riddled with waterways that past studies assumed did not hinder gene flow. We examined 1,858 base pairs of mitochondrial DNA sequenced from four gene regions in 14 birds (roughly 5% of the remaining population) found on the largest land masses of Andros Island (North Andros and Mangrove Cay/South Andros). We sought to discern genetic structuring between the remaining subpopulations and its relationship to current conservation concerns. Four unique haplotypes were identified, with only one shared between the two subpopulations. Nucleotide and haplotype diversity were higher for the North Andros subpopulation than for the Mangrove Cay/South Andros subpopulation. Analysis of molecular variance (AMOVA) yielded a Wright's fixation index (F st) of 0.60 (P Fst = 0.016), with 40.2% of the molecular variation explained by within-population differences and 59.8% by among-population differences. Based on the mitochondrial regions examined in this study, we suggest the extant subpopulations of Bahama Oriole exhibit significant population structuring over short distances, consistent with some other non-migratory tropical songbird species. PMID:26644974

  7. Early childhood family structure and mother-child interactions: variation by race and ethnicity.

    PubMed

    Gibson-Davis, Christina M; Gassman-Pines, Anna

    2010-01-01

    With data from the Early Childhood Longitudinal Study-Birth Cohort (n = 6,449), a nationally representative sample of births in 2001, we used hierarchical linear modeling to analyze differences in observed interactions between married, cohabiting, never-married, and divorced mothers and their children. In contrast to previous studies, we concentrated on early childhood, a developmentally critical period that has been understudied in the family structure literature, and relied on objective observational measures of mother-child interactions, which are unlikely to be biased by maternal perceptions of interactions with children. Nonmarital family structures were common in the lives of young children, as 32% lived outside of a married, biological parent home. Initial results indicated that married families were consistently associated with higher quality interactions. Moreover, though it was hypothesized that the presence of a biological father might be associated with higher quality interactions than single-parent households, this hypothesis was not confirmed. Additional models suggest that race and ethnicity moderated the effect of family structure, as non-Hispanic Black and non-Hispanic White participants showed little significant variation between married and unmarried families. Among Hispanics, mothers living in cohabiting, divorced, or single families, when compared to married mothers, exhibited more negative and more intrusive behaviors; cohabiting mothers also scored lower on the measure of cognitive stimulation. Results suggest that marriage may not be uniformly associated with higher levels of mother-child interactions and that cohabitation, particularly for Hispanics, may be associated with adverse outcomes. PMID:20053014

  8. Constraints on the Time Variation of the Fine Structure Constant by the 5-Year WMAP Data

    NASA Astrophysics Data System (ADS)

    Nakashima, M.; Nagata, R.; Yokoyama, J.

    2008-12-01

    The constraints on the time variation of the fine structure constant at recombination epoch relative to its present value, Δα/α ≡ (α_{rec} - α_{now})/α_{now}, are obtained from the analysis of the 5-year WMAP cosmic microwave background data. As a result of Markov-Chain Monte-Carlo analysis, it is found that, contrary to the analysis based on the previous WMAP data, the mean value of Δα/α = -0.0009 does not change significantly whether we use the Hubble Space Telescope (HST) measurement of the Hubble parameter as a prior or not. The resultant 95% confidence ranges of Δα/α are -0.028 < Δα/α < 0.026 with HST prior and -0.050 < Δα/α < 0.042 without HST prior.

  9. New constraints on variations of the fine structure constant from CMB anisotropies

    SciTech Connect

    Menegoni, Eloisa; Melchiorri, Alessandro; Galli, Silvia; Bartlett, James G.; Martins, C. J. A. P.

    2009-10-15

    We demonstrate that recent measurements of cosmic microwave background temperature and polarization anisotropy made by the ACBAR, QUAD, and BICEP experiments substantially improve the cosmological constraints on possible variations of the fine structure constant in the early universe. This data, combined with the five year observations from the WMAP mission, yield the constraint {alpha}/{alpha}{sub 0}=0.987{+-}0.012 at 68% C.L. The inclusion of the new Hubble Space Telescope constraints on the Hubble constant further increases the accuracy to {alpha}/{alpha}{sub 0}=1.001{+-}0.007 at 68% C.L., bringing possible deviations from the current value below the 1% level and improving previous constraints by a factor of {approx}3.

  10. Spatial and temporal variations in the age structure of Arctic sea ice

    USGS Publications Warehouse

    Belchansky, G.I.; Douglas, D.C.; Platonov, N.G.

    2005-01-01

    Spatial and temporal variations in the age structure of Arctic sea ice are investigated using a new reverse chronology algorithm that tracks ice-covered pixels to their location and date of origin based on ice motion and concentration data. The Beaufort Gyre tends to harbor the oldest (>10 years old) sea ice in the western Arctic while direct ice advection pathways toward the Transpolar Drift Stream maintain relatively young (10 years old (10+ year age class) were observed during 1989-2003. Since the mid-1990s, losses to the 10+ year age class lacked compensation by recruitment due to a prior depletion of all mature (6-10 year) age classes. Survival of the 1994 and 1996-1998 sea ice generations reestablished most mature age classes, and thereby the potential to increase extent of the 10+ year age class during the mid-2000s.

  11. Small angle neutron scattering study on the structural variation of lysozyme in bioprotectants

    NASA Astrophysics Data System (ADS)

    Koda, Shota; Takayama, Haruki; Shibata, Tomohiko; Mori, Tatsuya; Kojima, Seiji; Park, In-Sung; Shin, Tae-Gyu

    2015-05-01

    The thermal denaturation and subsequent structural variation of lysozyme in various bioprotectant candidate solutions such as trehalose and choline acetate have been investigated by using small angle neutron scattering and differential scanning calorimetry. The gyration radius shows little change with the addition of additives in a native state at room temperature. On heating the lysozyme solution, a remarkable increase in the gyration radius is observed at temperatures above the denaturation temperature without any bioprotectants. Such an increase is suppressed by the additives owing to the intermolecular interactions between the lysozyme molecules and the bioprotectants of trehalose and choline acetate. The fractal dimension of lysozyme varies slightly with the addition of the bioprotectant solutions, and shows a remarkable drop in the vicinity of the denaturation temperature for all the solutions.

  12. A phylogenetic backbone for Bivalvia: an RNA-seq approach

    PubMed Central

    González, Vanessa L.; Andrade, Sónia C. S.; Bieler, Rüdiger; Collins, Timothy M.; Dunn, Casey W.; Mikkelsen, Paula M.; Taylor, John D.; Giribet, Gonzalo

    2015-01-01

    Bivalves are an ancient and ubiquitous group of aquatic invertebrates with an estimated 10 000–20 000 living species. They are economically significant as a human food source, and ecologically important given their biomass and effects on communities. Their phylogenetic relationships have been studied for decades, and their unparalleled fossil record extends from the Cambrian to the Recent. Nevertheless, a robustly supported phylogeny of the deepest nodes, needed to fully exploit the bivalves as a model for testing macroevolutionary theories, is lacking. Here, we present the first phylogenomic approach for this important group of molluscs, including novel transcriptomic data for 31 bivalves obtained through an RNA-seq approach, and analyse these data with published genomes and transcriptomes of other bivalves plus outgroups. Our results provide a well-resolved, robust phylogenetic backbone for Bivalvia with all major lineages delineated, addressing long-standing questions about the monophyly of Protobranchia and Heterodonta, and resolving the position of particular groups such as Palaeoheterodonta, Archiheterodonta and Anomalodesmata. This now fully resolved backbone demonstrates that genomic approaches using hundreds of genes are feasible for resolving phylogenetic questions in bivalves and other animals. PMID:25589608

  13. Characterizing Aciniform Silk Repetitive Domain Backbone Dynamics and Hydrodynamic Modularity.

    PubMed

    Tremblay, Marie-Laurence; Xu, Lingling; Sarker, Muzaddid; Liu, Xiang-Qin; Rainey, Jan K

    2016-01-01

    Spider aciniform (wrapping) silk is a remarkable fibrillar biomaterial with outstanding mechanical properties. It is a modular protein consisting, in Argiope trifasciata, of a core repetitive domain of 200 amino acid units (W units). In solution, the W units comprise a globular folded core, with five α-helices, and disordered tails that are linked to form a ~63-residue intrinsically disordered linker in concatemers. Herein, we present nuclear magnetic resonance (NMR) spectroscopy-based (15)N spin relaxation analysis, allowing characterization of backbone dynamics as a function of residue on the ps-ns timescale in the context of the single W unit (W₁) and the two unit concatemer (W₂). Unambiguous mapping of backbone dynamics throughout W₂ was made possible by segmental NMR active isotope-enrichment through split intein-mediated trans-splicing. Spectral density mapping for W₁ and W₂ reveals a striking disparity in dynamics between the folded core and the disordered linker and tail regions. These data are also consistent with rotational diffusion behaviour where each globular domain tumbles almost independently of its neighbour. At a localized level, helix 5 exhibits elevated high frequency dynamics relative to the proximal helix 4, supporting a model of fibrillogenesis where this helix unfolds as part of the transition to a mixed α-helix/β-sheet fibre. PMID:27517921

  14. Long-term forecasting of internet backbone traffic.

    PubMed

    Papagiannaki, Konstantina; Taft, Nina; Zhang, Zhi-Li; Diot, Christophe

    2005-09-01

    We introduce a methodology to predict when and where link additions/upgrades have to take place in an Internet protocol (IP) backbone network. Using simple network management protocol (SNMP) statistics, collected continuously since 1999, we compute aggregate demand between any two adjacent points of presence (PoPs) and look at its evolution at time scales larger than 1 h. We show that IP backbone traffic exhibits visible long term trends, strong periodicities, and variability at multiple time scales. Our methodology relies on the wavelet multiresolution analysis (MRA) and linear time series models. Using wavelet MRA, we smooth the collected measurements until we identify the overall long-term trend. The fluctuations around the obtained trend are further analyzed at multiple time scales. We show that the largest amount of variability in the original signal is due to its fluctuations at the 12-h time scale. We model inter-PoP aggregate demand as a multiple linear regression model, consisting of the two identified components. We show that this model accounts for 98% of the total energy in the original signal, while explaining 90% of its variance. Weekly approximations of those components can be accurately modeled with low-order autoregressive integrated moving average (ARIMA) models. We show that forecasting the long term trend and the fluctuations of the traffic at the 12-h time scale yields accurate estimates for at least 6 months in the future. PMID:16252820

  15. Characterizing Aciniform Silk Repetitive Domain Backbone Dynamics and Hydrodynamic Modularity

    PubMed Central

    Tremblay, Marie-Laurence; Xu, Lingling; Sarker, Muzaddid; Liu, Xiang-Qin; Rainey, Jan K.

    2016-01-01

    Spider aciniform (wrapping) silk is a remarkable fibrillar biomaterial with outstanding mechanical properties. It is a modular protein consisting, in Argiope trifasciata, of a core repetitive domain of 200 amino acid units (W units). In solution, the W units comprise a globular folded core, with five α-helices, and disordered tails that are linked to form a ~63-residue intrinsically disordered linker in concatemers. Herein, we present nuclear magnetic resonance (NMR) spectroscopy-based 15N spin relaxation analysis, allowing characterization of backbone dynamics as a function of residue on the ps–ns timescale in the context of the single W unit (W1) and the two unit concatemer (W2). Unambiguous mapping of backbone dynamics throughout W2 was made possible by segmental NMR active isotope-enrichment through split intein-mediated trans-splicing. Spectral density mapping for W1 and W2 reveals a striking disparity in dynamics between the folded core and the disordered linker and tail regions. These data are also consistent with rotational diffusion behaviour where each globular domain tumbles almost independently of its neighbour. At a localized level, helix 5 exhibits elevated high frequency dynamics relative to the proximal helix 4, supporting a model of fibrillogenesis where this helix unfolds as part of the transition to a mixed α-helix/β-sheet fibre. PMID:27517921

  16. A phylogenetic backbone for Bivalvia: an RNA-seq approach.

    PubMed

    González, Vanessa L; Andrade, Sónia C S; Bieler, Rüdiger; Collins, Timothy M; Dunn, Casey W; Mikkelsen, Paula M; Taylor, John D; Giribet, Gonzalo

    2015-02-22

    Bivalves are an ancient and ubiquitous group of aquatic invertebrates with an estimated 10 000-20 000 living species. They are economically significant as a human food source, and ecologically important given their biomass and effects on communities. Their phylogenetic relationships have been studied for decades, and their unparalleled fossil record extends from the Cambrian to the Recent. Nevertheless, a robustly supported phylogeny of the deepest nodes, needed to fully exploit the bivalves as a model for testing macroevolutionary theories, is lacking. Here, we present the first phylogenomic approach for this important group of molluscs, including novel transcriptomic data for 31 bivalves obtained through an RNA-seq approach, and analyse these data with published genomes and transcriptomes of other bivalves plus outgroups. Our results provide a well-resolved, robust phylogenetic backbone for Bivalvia with all major lineages delineated, addressing long-standing questions about the monophyly of Protobranchia and Heterodonta, and resolving the position of particular groups such as Palaeoheterodonta, Archiheterodonta and Anomalodesmata. This now fully resolved backbone demonstrates that genomic approaches using hundreds of genes are feasible for resolving phylogenetic questions in bivalves and other animals. PMID:25589608

  17. Fast-slow continuum and reproductive strategies structure plant life-history variation worldwide.

    PubMed

    Salguero-Gómez, Roberto; Jones, Owen R; Jongejans, Eelke; Blomberg, Simon P; Hodgson, David J; Mbeau-Ache, Cyril; Zuidema, Pieter A; de Kroon, Hans; Buckley, Yvonne M

    2016-01-01

    The identification of patterns in life-history strategies across the tree of life is essential to our prediction of population persistence, extinction, and diversification. Plants exhibit a wide range of patterns of longevity, growth, and reproduction, but the general determinants of this enormous variation in life history are poorly understood. We use demographic data from 418 plant species in the wild, from annual herbs to supercentennial trees, to examine how growth form, habitat, and phylogenetic relationships structure plant life histories and to develop a framework to predict population performance. We show that 55% of the variation in plant life-history strategies is adequately characterized using two independent axes: the fast-slow continuum, including fast-growing, short-lived plant species at one end and slow-growing, long-lived species at the other, and a reproductive strategy axis, with highly reproductive, iteroparous species at one extreme and poorly reproductive, semelparous plants with frequent shrinkage at the other. Our findings remain consistent across major habitats and are minimally affected by plant growth form and phylogenetic ancestry, suggesting that the relative independence of the fast-slow and reproduction strategy axes is general in the plant kingdom. Our findings have similarities with how life-history strategies are structured in mammals, birds, and reptiles. The position of plant species populations in the 2D space produced by both axes predicts their rate of recovery from disturbances and population growth rate. This life-history framework may complement trait-based frameworks on leaf and wood economics; together these frameworks may allow prediction of responses of plants to anthropogenic disturbances and changing environments. PMID:26699477

  18. Fast–slow continuum and reproductive strategies structure plant life-history variation worldwide

    PubMed Central

    Salguero-Gómez, Roberto; Jones, Owen R.; Jongejans, Eelke; Blomberg, Simon P.; Hodgson, David J.; Mbeau-Ache, Cyril; Zuidema, Pieter A.; de Kroon, Hans; Buckley, Yvonne M.

    2016-01-01

    The identification of patterns in life-history strategies across the tree of life is essential to our prediction of population persistence, extinction, and diversification. Plants exhibit a wide range of patterns of longevity, growth, and reproduction, but the general determinants of this enormous variation in life history are poorly understood. We use demographic data from 418 plant species in the wild, from annual herbs to supercentennial trees, to examine how growth form, habitat, and phylogenetic relationships structure plant life histories and to develop a framework to predict population performance. We show that 55% of the variation in plant life-history strategies is adequately characterized using two independent axes: the fast–slow continuum, including fast-growing, short-lived plant species at one end and slow-growing, long-lived species at the other, and a reproductive strategy axis, with highly reproductive, iteroparous species at one extreme and poorly reproductive, semelparous plants with frequent shrinkage at the other. Our findings remain consistent across major habitats and are minimally affected by plant growth form and phylogenetic ancestry, suggesting that the relative independence of the fast–slow and reproduction strategy axes is general in the plant kingdom. Our findings have similarities with how life-history strategies are structured in mammals, birds, and reptiles. The position of plant species populations in the 2D space produced by both axes predicts their rate of recovery from disturbances and population growth rate. This life-history framework may complement trait-based frameworks on leaf and wood economics; together these frameworks may allow prediction of responses of plants to anthropogenic disturbances and changing environments. PMID:26699477

  19. Variation and fitness costs for tolerance to different types of herbivore damage in Boechera stricta genotypes with contrasting glucosinolate structures

    PubMed Central

    Manzaneda, Antonio J.; Prasad, Kasavajhala V. S. K.; Mitchell-Olds, Thomas

    2010-01-01

    Summary Analyses of plant tolerance in response to different modes of herbivory are essential to understand plant defense evolution, yet are still scarce. Allocation costs and trade-offs between tolerance and plant chemical defenses may influence genetic variation for tolerance. However, variation in defenses occurs also for presence or absence of discrete chemical structures, yet, effects of intra-specific polymorphisms on tolerance to multiple herbivores have not been evaluated.Here, in a glasshouse experiment, we investigated variation for tolerance to different types of herbivory damage, and direct allocation costs in 10 genotypes of Boechera stricta (Brassicaceae), a wild relative of Arabidopsis, with contrasting foliar glucosinolate chemical structures (methionine-derived glucosinolates vs glucosinolates derived from branched-chain amino acids).We found significant genetic variation for tolerance to different types of herbivory. Structural variations in the glucosinolate profile did not influence tolerance to damage, but predicted plant fitness. Levels of constitutive and induced glucosinolates varied between genotypes with different structural profiles, but we did not detect any cost of tolerance explaining genetic variation in tolerance among genotypes.Trade-offs among plant tolerance to multiple herbivores may not explain the existence of intermediate levels of tolerance to damage in plants with contrasting chemical defensive profiles. PMID:20663059

  20. Low Molecular Weight Oligomers with Aromatic Backbone as Efficient Nonviral Gene Vectors.

    PubMed

    Luan, Chao-Ran; Liu, Yan-Hong; Zhang, Ji; Yu, Qing-Ying; Huang, Zheng; Wang, Bing; Yu, Xiao-Qi

    2016-05-01

    A series of oligomers were synthesized via ring-opening polymerization. Although the molecular weights of these oligomers are only ∼2.5 kDa, they could efficiently bind and condense DNA into nanoparticles. These oligomers gave comparable transfection efficiency (TE) to PEI 25 kDa, while their TE could even increase with the presence of serum, and up to 65 times higher TE than PEI was obtained. The excellent serum tolerance was also confirmed by TEM, flow cytometry, and BSA adsorption assay. Moreover, structure-activity relationship studies revealed some interesting factors. First, oligomers containing aromatic rings in the backbone showed better DNA binding ability. These materials could bring more DNA cargo into the cells, leading to much better TE. Second, the isomerism of the disubstituted phenyl group on the oligomer backbone has large effect on the transfection. The ortho-disubstituted ones gave at least 1 order of magnitude higher TE than meta- or para-disubstituted oligomers. Gel electrophoresis involving DNase and heparin indicated that the difficulty to release DNA might contribute to the lower TE of the latter. Such clues may help us to design novel nonviral gene vectors with high efficiency and biocompatibility. PMID:27077449

  1. The Nanomechanical Properties of Lactococcus lactis Pili Are Conditioned by the Polymerized Backbone Pilin

    PubMed Central

    Castelain, Mickaël; Duviau, Marie-Pierre; Canette, Alexis; Schmitz, Philippe; Loubière, Pascal; Cocaign-Bousquet, Muriel; Piard, Jean-Christophe; Mercier-Bonin, Muriel

    2016-01-01

    Pili produced by Lactococcus lactis subsp. lactis are putative linear structures consisting of repetitive subunits of the major pilin PilB that forms the backbone, pilin PilA situated at the distal end of the pilus, and an anchoring pilin PilC that tethers the pilus to the peptidoglycan. We determined the nanomechanical properties of pili using optical-tweezers force spectroscopy. Single pili were exposed to optical forces that yielded force-versus-extension spectra fitted using the Worm-Like Chain model. Native pili subjected to a force of 0–200 pN exhibit an inextensible, but highly flexible ultrastructure, reflected by their short persistence length. We tested a panel of derived strains to understand the functional role of the different pilins. First, we found that both the major pilin PilB and sortase C organize the backbone into a full-length organelle and dictate the nanomechanical properties of the pili. Second, we found that both PilA tip pilin and PilC anchoring pilin were not essential for the nanomechanical properties of pili. However, PilC maintains the pilus on the bacterial surface and may play a crucial role in the adhesion- and biofilm-forming properties of L. lactis. PMID:27010408

  2. Simultaneous alignment and folding of 28S rRNA sequences uncovers phylogenetic signal in structure variation.

    PubMed

    Letsch, Harald O; Greve, Carola; Kück, Patrick; Fleck, Günther; Stocsits, Roman R; Misof, Bernhard

    2009-12-01

    Secondary structure models of mitochondrial and nuclear (r)RNA sequences are frequently applied to aid the alignment of these molecules in phylogenetic analyses. Additionally, it is often speculated that structure variation of (r)RNA sequences might profitably be used as phylogenetic markers. The benefit of these approaches depends on the reliability of structure models. We used a recently developed approach to show that reliable inference of large (r)RNA secondary structures as a prerequisite of simultaneous sequence and structure alignment is feasible. The approach iteratively establishes local structure constraints of each sequence and infers fully folded individual structures by constrained MFE optimization. A comparison of structure edit distances of individual constraints and fully folded structures showed pronounced phylogenetic signal in fully folded structures. As model sequences we characterized secondary structures of 28S rRNA sequences of selected insects and examined their phylogenetic signal according to established phylogenetic hypotheses. PMID:19654047

  3. Physico-chemical properties and cytotoxic effects of sugar-based surfactants: Impact of structural variations.

    PubMed

    Lu, Biao; Vayssade, Muriel; Miao, Yong; Chagnault, Vincent; Grand, Eric; Wadouachi, Anne; Postel, Denis; Drelich, Audrey; Egles, Christophe; Pezron, Isabelle

    2016-09-01

    Surfactants derived from the biorefinery process can present interesting surface-active properties, low cytotoxicity, high biocompatibility and biodegradability. They are therefore considered as potential sustainable substitutes to currently used petroleum-based surfactants. To better understand and anticipate their performances, structure-property relationships need to be carefully investigated. For this reason, we applied a multidisciplinary approach to systematically explore the effect of subtle structural variations on both physico-chemical properties and biological effects. Four sugar-based surfactants, each with an eight carbon alkyl chain bound to a glucose or maltose head group by an amide linkage, were synthesized and evaluated together along with two commercially available standard surfactants. Physico-chemical properties including solubility, Krafft point, surface-tension lowering and critical micellar concentration (CMC) in water and biological medium were explored. Cytotoxicity evaluation by measuring proliferation index and metabolic activity against dermal fibroblasts showed that all surfactants studied may induce cell death at low concentrations (below their CMC). Results revealed significant differences in both physico-chemical properties and cytotoxic effects depending on molecule structural features, such as the position of the linkage on the sugar head-group, or the orientation of the amide linkage. Furthermore, the cytotoxic response increased with the reduction of surfactant CMC. This study underscores the relevance of a methodical and multidisciplinary approach that enables the consideration of surfactant solution properties when applied to biological materials. Overall, our results will contribute to a better understanding of the concomitant impact of surfactant structure at physico-chemical and biological levels. PMID:27137806

  4. Sequence-dependent Structural Variation in DNA Undergoing Intrahelical Inspection by the DNA glycosylase MutM

    SciTech Connect

    Sung, Rou-Jia; Zhang, Michael; Qi, Yan; Verdine, Gregory L.

    2012-08-31

    MutM, a bacterial DNA-glycosylase, plays a critical role in maintaining genome integrity by catalyzing glycosidic bond cleavage of 8-oxoguanine (oxoG) lesions to initiate base excision DNA repair. The task faced by MutM of locating rare oxoG residues embedded in an overwhelming excess of undamaged bases is especially challenging given the close structural similarity between oxoG and its normal progenitor, guanine (G). MutM actively interrogates the DNA to detect the presence of an intrahelical, fully base-paired oxoG, whereupon the enzyme promotes extrusion of the target nucleobase from the DNA duplex and insertion into the extrahelical active site. Recent structural studies have begun to provide the first glimpse into the protein-DNA interactions that enable MutM to distinguish an intrahelical oxoG from G; however, these initial studies left open the important question of how MutM can recognize oxoG residues embedded in 16 different neighboring sequence contexts (considering only the 5'- and 3'-neighboring base pairs). In this study we set out to understand the manner and extent to which intrahelical lesion recognition varies as a function of the 5'-neighbor. Here we report a comprehensive, systematic structural analysis of the effect of the 5'-neighboring base pair on recognition of an intrahelical oxoG lesion. These structures reveal that MutM imposes the same extrusion-prone ('extrudogenic') backbone conformation on the oxoG lesion irrespective of its 5'-neighbor while leaving the rest of the DNA relatively free to adjust to the particular demands of individual sequences.

  5. Increased Diels-Alderase activity through backbone remodeling guided by Foldit players.

    PubMed

    Eiben, Christopher B; Siegel, Justin B; Bale, Jacob B; Cooper, Seth; Khatib, Firas; Shen, Betty W; Players, Foldit; Stoddard, Barry L; Popovic, Zoran; Baker, David

    2012-02-01

    Computational enzyme design holds promise for the production of renewable fuels, drugs and chemicals. De novo enzyme design has generated catalysts for several reactions, but with lower catalytic efficiencies than naturally occurring enzymes. Here we report the use of game-driven crowdsourcing to enhance the activity of a computationally designed enzyme through the functional remodeling of its structure. Players of the online game Foldit were challenged to remodel the backbone of a computationally designed bimolecular Diels-Alderase to enable additional interactions with substrates. Several iterations of design and characterization generated a 24-residue helix-turn-helix motif, including a 13-residue insertion, that increased enzyme activity >18-fold. X-ray crystallography showed that the large insertion adopts a helix-turn-helix structure positioned as in the Foldit model. These results demonstrate that human creativity can extend beyond the macroscopic challenges encountered in everyday life to molecular-scale design problems. PMID:22267011

  6. Three-dimensional structure of the extended solar magnetic field and the sunspot cycle variation in cosmic ray intensity

    NASA Technical Reports Server (NTRS)

    Svalgaard, L.; Wilcox, J. M.

    1976-01-01

    A principal cause for the eleven-year sunspot cycle variation in the primary cosmic ray intensity observed at earth may be a variation in the solid angle of the heliosphere occupied by the extended solar polar magnetic field. Galactic cosmic rays have relatively easy access to the inner solar system through the regular extended solar polar fields, and relatively difficult access through the irregular extended solar sector structure fields.

  7. Hygroscopic movements in Geraniaceae: the structural variations that are responsible for coiling or bending.

    PubMed

    Abraham, Yael; Elbaum, Rivka

    2013-07-01

    The family Geraniaceae is characterized by a beak-like fruit, consisting of five seeds appended by a tapering awn. The awns exhibit coiling or bending hygroscopic movement as part of the seed dispersal strategy. Here we explain the variation in the hygroscopic reaction based on structural principles. We examined five representative species from three genera: Erodium, Geranium, and Pelargonium. Using X-ray diffraction, and electron and polarized light microscopy, we measured the cellulose microfibril angles in relation to the cell and cellulose helix axes. The behavior of separated single cells during dehydration was also examined. A bi-layered structure characterizes all the representative genera studied, with a hygroscopically contracting inner layer, and a stiff outer layer. We found that the cellulose arrangement in the inner layer is responsible for the type of awn deformation (coiling or bending). In three of the five awns examined, we identified an additional coiling outer sublayer, which adds coiling deformation to the awn. We divide the movements into three types: bending, coiling, and coiled-bending. All movement types are found in the Geranium genus. These characteristics are of importance for understanding the evolution of seed dispersal mechanisms in the Geraniaceae family. PMID:23574364

  8. A model-reduction approach in micromechanics of materials preserving the variational structure of constitutive relations

    NASA Astrophysics Data System (ADS)

    Michel, Jean-Claude; Suquet, Pierre

    2016-05-01

    In 2003 the authors proposed a model-reduction technique, called the Nonuniform Transformation Field Analysis (NTFA), based on a decomposition of the local fields of internal variables on a reduced basis of modes, to analyze the effective response of composite materials. The present study extends and improves on this approach in different directions. It is first shown that when the constitutive relations of the constituents derive from two potentials, this structure is passed to the NTFA model. Another structure-preserving model, the hybrid NTFA model of Fritzen and Leuschner, is analyzed and found to differ (slightly) from the primal NTFA model (it does not exhibit the same variational upper bound character). To avoid the "on-line" computation of local fields required by the hybrid model, new reduced evolution equations for the reduced variables are proposed, based on an expansion to second order (TSO) of the potential of the hybrid model. The coarse dynamics can then be entirely expressed in terms of quantities which can be pre-computed once for all. Roughly speaking, these pre-computed quantities depend only on the average and fluctuations per phase of the modes and of the associated stress fields. The accuracy of the new NTFA-TSO model is assessed by comparison with full-field simulations. The acceleration provided by the new coarse dynamics over the full-field computations (and over the hybrid model) is then spectacular, larger by three orders of magnitude than the acceleration due to the sole reduction of unknowns.

  9. Temporal Variation in Genetic Diversity and Structure of a Lotic Population of Burkholderia (Pseudomonas) cepacia

    PubMed Central

    Wise, M. G.; McArthur, J. V.; Wheat, C.; Shimkets, L. J.

    1996-01-01

    The genetic structure and temporal patterns of genetic diversity in a population of Burkholderia (Pseudomonas) cepacia, isolated from a southeastern blackwater stream, were investigated by multilocus enzyme electrophoresis. Allelic variation in seven structural gene loci was monitored at a single stream location at 0, 6, 12, and 24 h and at 2, 4, 8, 16, and 32 days. Over the length of the study, 217 isolates were collected, from which 65 unique electrophoretic types (ETs) were identified. Most of these ETs were present at only one or two time periods and were considered transients; however, one resident ET was particularly abundant (64 of the 217 isolates [29.4%]) and was found at all time points except day 32. The mean genetic diversity of the entire population was 0.520, and the index of association (a measure of multilocus linkage disequilibrium) was 1.33. These results, taken in conjunction with a previous study focusing on spatial patterns of genetic diversity in lotic B. cepacia, show that these bacterial populations exhibit greater variability among sites than within a site over time, suggesting relative stability over short time periods. PMID:16535308

  10. Spatial-temporal variation of precipitation concentration and structure in the Wei River Basin, China

    NASA Astrophysics Data System (ADS)

    Huang, Shengzhi; Huang, Qiang; Chen, Yutong; Xing, Li; Leng, Guoyong

    2015-05-01

    It is of significant importance to investigate precipitation structure and precipitation concentration due to their great impact on droughts, floods, soil erosion, as well as water resources management. A complete investigation of precipitation structure and its distribution pattern in the Wei River Basin was performed based on recorded daily precipitation data in this study. Two indicators were used: concentration index based on daily precipitation (CID), to assess the distribution of rainy days, and concentration index based on monthly precipitation (CIM), to estimate the seasonality of the precipitation. Besides, the modified Mann-Kendall trend test method was employed to capture the variation trends of CID and CIM. The results indicate that: (1) the 1-3-day events are the predominant precipitation events in terms of the occurrence and fractional contribution; (2) the obvious differences in the CID of various areas are found in the Wei River Basin, and the high CID values mainly concentrate in the northern basin, conversely, the southern basin has a relatively low CID value; (3) high CIM values are primarily in the western and northern basin, reflecting a remarkable seasonality of precipitation in these regions; and (4) all of the stations show a downward trend of CIM, which indicates that the monthly precipitation distribution tends to be more uniform.

  11. Structure of Ground state Wave Functions for the Fractional Quantum Hall Effect: A Variational Approach

    NASA Astrophysics Data System (ADS)

    Mukherjee, Sutirtha; Mandal, Sudhansu

    The internal structure and topology of the ground states for fractional quantum Hall effect (FQHE) are determined by the relative angular momenta between all the possible pairs of electrons. Laughlin wave function is the only known microscopic wave function for which these relative angular momenta are homogeneous (same) for any pair of electrons and depend solely on the filling factor. Without invoking any microscopic theory, considering only the relationship between number of flux quanta and particles in spherical geometry, and allowing the possibility of inhomogeneous (different) relative angular momenta between any two electrons, we develop a general method for determining a closed-form ground state wave function for any incompressible FQHE state. Our procedure provides variationally obtained very accurate wave functions, yet having simpler structure compared to any other known complex microscopic wave functions for the FQHE states. This method, thus, has potential in predicting a very accurate ground state wave function for the puzzling states such as the state at filling fraction 5/2. We acknowledge support from Department of Science and Technology, India.

  12. Large-scale variation in lithospheric structure along and across the Kenya rift

    USGS Publications Warehouse

    Prodehl, C.; Mechie, J.; Kaminski, W.; Fuchs, K.; Grosse, C.; Hoffmann, H.; Stangl, R.; Stellrecht, R.; Khan, M.A.; Maguire, Peter K.H.; Kirk, W.; Keller, Gordon R.; Githui, A.; Baker, M.; Mooney, W.; Criley, E.; Luetgert, J.; Jacob, B.; Thybo, H.; Demartin, M.; Scarascia, S.; Hirn, A.; Bowman, J.R.; Nyambok, I.; Gaciri, S.; Patel, J.; Dindi, E.; Griffiths, D.H.; King, R.F.; Mussett, A.E.; Braile, L.W.; Thompson, G.; Olsen, K.; Harder, S.; Vees, R.; Gajewski, D.; Schulte, A.; Obel, J.; Mwango, F.; Mukinya, J.; Riaroh, D.

    1991-01-01

    The Kenya rift is one of the classic examples of a continental rift zone: models for its evolution range from extension of the lithosphere by pure shear1, through extension by simple shear2, to diapiric upwelling of an asthenolith3. Following a pilot study in 19854, the present work involved the shooting of three seismic refraction and wide-angle reflection profiles along the axis, across the margins, and on the northeastern flank of the rift (Fig. 1). These lines were intended to reconcile the different crustal thickness estimates for the northern and southern parts of the rift4-6 and to reveal the structure across the rift, including that beneath the flanks. The data, presented here, reveal significant lateral variations in structure both along and across the rift. The crust thins along the rift axis from 35 km in the south to 20 km in the north; there are abrupt changes in Mono depth and uppermost-mantle seismic velocity across the rift margins, and crustal thickening across the boundary between the Archaean craton and PanAfrican orogenic belt immediately west of the rift. These results suggest that thickened crust may have controlled the rift's location, that there is a decrease in extension from north to south, and that the upper mantle immediately beneath the rift may contain reservoirs of magma generated at greater depth.

  13. Spatial-temporal variation of precipitation concentration and structure in the Wei River Basin, China

    NASA Astrophysics Data System (ADS)

    Huang, Shengzhi; Huang, Qiang; Chen, Yutong; Xing, Li; Leng, Guoyong

    2016-07-01

    It is of significant importance to investigate precipitation structure and precipitation concentration due to their great impact on droughts, floods, soil erosion, as well as water resources management. A complete investigation of precipitation structure and its distribution pattern in the Wei River Basin was performed based on recorded daily precipitation data in this study. Two indicators were used: concentration index based on daily precipitation (CID), to assess the distribution of rainy days, and concentration index based on monthly precipitation (CIM), to estimate the seasonality of the precipitation. Besides, the modified Mann-Kendall trend test method was employed to capture the variation trends of CID and CIM. The results indicate that: (1) the 1-3-day events are the predominant precipitation events in terms of the occurrence and fractional contribution; (2) the obvious differences in the CID of various areas are found in the Wei River Basin, and the high CID values mainly concentrate in the northern basin, conversely, the southern basin has a relatively low CID value; (3) high CIM values are primarily in the western and northern basin, reflecting a remarkable seasonality of precipitation in these regions; and (4) all of the stations show a downward trend of CIM, which indicates that the monthly precipitation distribution tends to be more uniform.

  14. Variation in forest structure and carbon dynamics in tropical rain forests of Amazonia

    NASA Astrophysics Data System (ADS)

    Vieira, S.; Selhorst, D.; Hutyra, L.; da Silva, R.; Camargo, P.; Chambers, J. Q.; Brown, I. F.; Higuchi, N.; Dos Santos, J.; Martinelli, L. A.; Trumbore, S.

    2002-12-01

    A better understanding of the variations in the dynamics and structure of trees in tropical forests is necessary for predicting the potential for these ecosystems to lose or store carbon. Data from forest inventory plotsshow large differences in forest structure, biomass, and tree growth rates among plots in three location. The number of stems (g.t. 10cm diameter)per hectare is higher in the Manaus site (626 ha-1) than in the Rio Branco (466 ha-1) or Santrem (460 ha-1) sites. Stocks of C in above-ground biomass in the three areas were 180.1 (Manaus), 122.1 (Rio Branco), and 140.6 (Santarem) MgC ha-1. Estimates of mean annual accumulation of C in living trees based on monthly dendrometer band measurements ranged from 1.6 (Manaus), 2.5 (Rio Branco), to 2.8 (Santarem) MgC ha-1 yr-1. Our results showed marked seasonality to growth, with highest growth rates in the wet and lowest rates in the dry season. This effect was most pronounced for trees with diameter g. t. 50cm. Comparing the three areas investigated suggests that forests experiencing a longer dry season have larger annual diameter growth increments for individual trees, and more of the forest biomass in the largest trees.

  15. Constraining the variation of the fine-structure constant with observations of narrow quasar absorption lines

    SciTech Connect

    Songaila, A.; Cowie, L. L.

    2014-10-01

    The unequivocal demonstration of temporal or spatial variability in a fundamental constant of nature would be of enormous significance. Recent attempts to measure the variability of the fine-structure constant α over cosmological time, using high-resolution spectra of high-redshift quasars observed with 10 m class telescopes, have produced conflicting results. We use the many multiplet (MM) method with Mg II and Fe II lines on very high signal-to-noise, high-resolution (R = 72, 000) Keck HIRES spectra of eight narrow quasar absorption systems. We consider both systematic uncertainties in spectrograph wavelength calibration and also velocity offsets introduced by complex velocity structure in even apparently simple and weak narrow lines and analyze their effect on claimed variations in α. We find no significant change in α, Δα/α = (0.43 ± 0.34) × 10{sup –5}, in the redshift range z = 0.7-1.5, where this includes both statistical and systematic errors. We also show that the scatter in measurements of Δα/α arising from absorption line structure can be considerably larger than assigned statistical errors even for apparently simple and narrow absorption systems. We find a null result of Δα/α = (– 0.59 ± 0.55) × 10{sup –5} in a system at z = 1.7382 using lines of Cr II, Zn II, and Mn II, whereas using Cr II and Zn II lines in a system at z = 1.6614 we find a systematic velocity trend that, if interpreted as a shift in α, would correspond to Δα/α = (1.88 ± 0.47) × 10{sup –5}, where both results include both statistical and systematic errors. This latter result is almost certainly caused by varying ionic abundances in subcomponents of the line: using Mn II, Ni II, and Cr II in the analysis changes the result to Δα/α = (– 0.47 ± 0.53) × 10{sup –5}. Combining the Mg II and Fe II results with estimates based on Mn II, Ni II, and Cr II gives Δα/α = (– 0.01 ± 0.26) × 10{sup –5}. We conclude that spectroscopic measurements of

  16. Variations in community structure and diversity associated with methane-rich sediments offshore southwestern Taiwan

    NASA Astrophysics Data System (ADS)

    Lin, L.; Lin, J.; Wu, L.; Wang, P.

    2012-12-01

    Subseafloor sediments have been estimated to harbor more than 50% of the global prokaryotic cells. Such a large quantity of biomass has been considered to play an important role in regulating the elemental cycling between hydrosphere, atmosphere, and geosphere. On the basis of pore water geochemistry and molecular results, numerous studies have demonstrated that sulfate reduction, anaerobic methanotrophy, and methanogenesis appear to be the essential metabolic pathways controlling the organic mineralization and methane cycling in sediments of continental margins. As the extent of microbial community varies from site to site, spatial variations in community structures directly or indirectly catalyzing these metabolic pathways remain to be elucidated. This study aims to uncover community structures along a sediment core collected offshore southwestern Taiwan where the convergence between the Eurasian and Philippine Sea Plates leads to the rapid accumulation of sediments eroded from onshore mountainous regions. The samples were obtained at a 50-cm interval from a gravity core which penetrated to 5 m below seafloor. Crude DNA was extracted and the V4-V6 and V4-V5 regions of 16S rRNA genes in bacteria and archaea were amplified using the barcoded primers, respectively. The amplicons were pooled for sequencing on a Roche GS Junior platform. A total of more than 130,000 bacterial and archaeal reads each were obtained after the processing of raw data for quality check, and chimera, barcode and primer removals. The output reads were clustered into different OTU on the basis of 97% similarity and taxonomically categorized against the Silva database. Despite a significant proportion of sequences whose taxonomical assignments remain to be resolved, sequences affiliated with Firmicutes, Proteobacteria and Chloroflexi within Bacteria, and Thermoplasmata, MBG-B, ANME-1, and MCG within Archaea outnumber the other lineages. The proportions of major OTUs exhibit different trends of

  17. Constraining the Variation of the Fine-structure Constant with Observations of Narrow Quasar Absorption Lines

    NASA Astrophysics Data System (ADS)

    Songaila, A.; Cowie, L. L.

    2014-10-01

    The unequivocal demonstration of temporal or spatial variability in a fundamental constant of nature would be of enormous significance. Recent attempts to measure the variability of the fine-structure constant α over cosmological time, using high-resolution spectra of high-redshift quasars observed with 10 m class telescopes, have produced conflicting results. We use the many multiplet (MM) method with Mg II and Fe II lines on very high signal-to-noise, high-resolution (R = 72, 000) Keck HIRES spectra of eight narrow quasar absorption systems. We consider both systematic uncertainties in spectrograph wavelength calibration and also velocity offsets introduced by complex velocity structure in even apparently simple and weak narrow lines and analyze their effect on claimed variations in α. We find no significant change in α, Δα/α = (0.43 ± 0.34) × 10-5, in the redshift range z = 0.7-1.5, where this includes both statistical and systematic errors. We also show that the scatter in measurements of Δα/α arising from absorption line structure can be considerably larger than assigned statistical errors even for apparently simple and narrow absorption systems. We find a null result of Δα/α = (- 0.59 ± 0.55) × 10-5 in a system at z = 1.7382 using lines of Cr II, Zn II, and Mn II, whereas using Cr II and Zn II lines in a system at z = 1.6614 we find a systematic velocity trend that, if interpreted as a shift in α, would correspond to Δα/α = (1.88 ± 0.47) × 10-5, where both results include both statistical and systematic errors. This latter result is almost certainly caused by varying ionic abundances in subcomponents of the line: using Mn II, Ni II, and Cr II in the analysis changes the result to Δα/α = (- 0.47 ± 0.53) × 10-5. Combining the Mg II and Fe II results with estimates based on Mn II, Ni II, and Cr II gives Δα/α = (- 0.01 ± 0.26) × 10-5. We conclude that spectroscopic measurements of quasar absorption lines are not yet capable of

  18. Living in isolation – population structure, reproduction, and genetic variation of the endangered plant species Dianthus gratianopolitanus (Cheddar pink)

    PubMed Central

    Putz, Christina M; Schmid, Christoph; Reisch, Christoph

    2015-01-01

    The endangered plant species Dianthus gratianopolitanus exhibits a highly fragmented distribution range comprising many isolated populations. Based upon this pattern of distribution, we selected a study region in Switzerland with a lower magnitude of isolation (Swiss Jura) and another study region in Germany with a higher degree of isolation (Franconian Jura). In each region, we chose ten populations to analyze population structure, reproduction, and genetic variation in a comparative approach. Therefore, we determined population density, cushion size, and cushion density to analyze population structure, investigated reproductive traits, including number of flowers, capsules, and germination rate, and analyzed amplified fragment length polymorphisms to study genetic variation. Population and cushion density were credibly higher in German than in Swiss populations, whereas reproductive traits and genetic variation within populations were similar in both study regions. However, genetic variation among populations and isolation by distance were stronger in Germany than in Switzerland. Generally, cushion size and density as well as flower and capsule production increased with population size and density, whereas genetic variation decreased with population density. In contrast to our assumptions, we observed denser populations and cushions in the region with the higher magnitude of isolation, whereas reproductive traits and genetic variation within populations were comparable in both regions. This corroborates the assumption that stronger isolation must not necessarily result in the loss of fitness and genetic variation. Furthermore, it supports our conclusion that the protection of strongly isolated populations contributes essentially to the conservation of a species' full evolutionary potential. PMID:26380690

  19. Backbone dynamics of barstar: a (15)N NMR relaxation study.

    PubMed

    Sahu, S C; Bhuyan, A K; Majumdar, A; Udgaonkar, J B

    2000-12-01

    Backbone dynamics of uniformly (15)N-labeled barstar have been studied at 32 degrees C, pH 6.7, by using (15)N relaxation data obtained from proton-detected 2D (1)H-(15)N NMR spectroscopy. (15)N spin-lattice relaxation rate constants (R(1)), spin-spin relaxation rate constants (R(2)), and steady-state heteronuclear (1)H-(15)N NOEs have been determined for 69 of the 86 (excluding two prolines and the N-terminal residue) backbone amide (15)N at a magnetic field strength of 14.1 Tesla. The primary relaxation data have been analyzed by using the model-free formalism of molecular dynamics, using both isotropic and axially symmetric diffusion of the molecule, to determine the overall rotational correlation time (tau(m)), the generalized order parameter (S(2)), the effective correlation time for internal motions (tau(e)), and NH exchange broadening contributions (R(ex)) for each residue. As per the axially symmetric diffusion, the ratio of diffusion rates about the unique and perpendicular axes (D( parallel)/D( perpendicular)) is 0.82 +/- 0.03. The two results have only marginal differences. The relaxation data have also been used to map reduced spectral densities for the NH vectors of these residues at three frequencies: 0, omega(H), and omega(N), where omega(H),(N) are proton and nitrogen Larmor frequencies. The value of tau(m) obtained from model-free analysis of the relaxation data is 5.2 ns. The reduced spectral density analysis, however, yields a value of 5.7 ns. The tau(m) determined here is different from that calculated previously from time-resolved fluorescence data (4.1 ns). The order parameter ranges from 0.68 to 0.98, with an average value of 0.85 +/- 0.02. A comparison of the order parameters with the X-ray B-factors for the backbone nitrogens of wild-type barstar does not show any considerable correlation. Model-free analysis of the relaxation data for seven residues required the inclusion of an exchange broadening term, the magnitude of which ranges from 2

  20. Investigations of secular variations spatial structure in the Ukrainian repeat stations network

    NASA Astrophysics Data System (ADS)

    Maksymchuk, V.; Horodyskyy, Yu.

    2009-04-01

    spring season indicate seasonal nature of such effects. These seasonal anomalies are connected with peculiarities of hydro-regulations and changes in subterranean waters level, depending from spring rains, snow thawing and strengthening of nature filtering processes in upper layer of sediments. Last one may cause appearance of anomalous changes in magnetic field due to electro-kinetic phenomena caused by filtrating. To define electro-magnetic precursors of local earthquakes also were fulfilled magnetic-variation observations by means of digital station LEMI. Vectors of induction in the range 2.5 - 60 min. for DP-variations were calculated. Time series analysis for induction vectors components allows to define their season, daily and episodically variations. Unambiguous connection of anomalous induction vectors values with local earthquakes were not defined. So, for 29 earthquakes with M≤3 in the range of 30 km during 2000 - 2004 only in 10 cases (34%) anomalous values of induction vectors preceded seismic events, in 11 cases they were observed after earthquakes (38%). At the same time, some peculiarities of spatial distribution for earthquakes with anomalous induction vectors distribution were observed. It was determined that for earthquakes with epicenters near Transcarpathian deep fault anomalous values of induction arrows can be observed before an earthquake. And for earthquakes with epicenters in the central part of the Carpathian backdeep - after an earthquake. Probably, in the Transcarpathian deep fault zone take place some changes in electric conductivity before earthquake. This result agrees with a hypothesis that a nature of electric-conductivity Transcarpathian anomaly was caused by partial melting of rocks with presence of water, but not by presence of graphitic sediments. And in the Carpathian backdeep changes of electric-conductivity are the result of structural elements destruction. For more confident conclusions concerning defined problem it is necessary

  1. Geographic Variation in Plant Community Structure of Salt Marshes: Species, Functional and Phylogenetic Perspectives

    PubMed Central

    Guo, Hongyu; Chamberlain, Scott A.; Elhaik, Eran; Jalli, Inder; Lynes, Alana-Rose; Marczak, Laurie; Sabath, Niv; Vargas, Amy; Więski, Kazimierz; Zelig, Emily M.; Pennings, Steven C.

    2015-01-01

    In general, community similarity is thought to decay with distance; however, this view may be complicated by the relative roles of different ecological processes at different geographical scales, and by the compositional perspective (e.g. species, functional group and phylogenetic lineage) used. Coastal salt marshes are widely distributed worldwide, but no studies have explicitly examined variation in salt marsh plant community composition across geographical scales, and from species, functional and phylogenetic perspectives. Based on studies in other ecosystems, we hypothesized that, in coastal salt marshes, community turnover would be more rapid at local versus larger geographical scales; and that community turnover patterns would diverge among compositional perspectives, with a greater distance decay at the species level than at the functional or phylogenetic levels. We tested these hypotheses in salt marshes of two regions: The southern Atlantic and Gulf Coasts of the United States. We examined the characteristics of plant community composition at each salt marsh site, how community similarity decayed with distance within individual salt marshes versus among sites in each region, and how community similarity differed among regions, using species, functional and phylogenetic perspectives. We found that results from the three compositional perspectives generally showed similar patterns: there was strong variation in community composition within individual salt marsh sites across elevation; in contrast, community similarity decayed with distance four to five orders of magnitude more slowly across sites within each region. Overall, community dissimilarity of salt marshes was lowest on the southern Atlantic Coast, intermediate on the Gulf Coast, and highest between the two regions. Our results indicated that local gradients are relatively more important than regional processes in structuring coastal salt marsh communities. Our results also suggested that in

  2. Tuning polyelectrolyte multilayer structure by exploiting natural variation in fucoidan chemistry.

    PubMed

    Ho, Tracey T M; Bremmell, Kristen E; Krasowska, Marta; Stringer, Damien N; Thierry, Benjamin; Beattie, David A

    2015-03-21

    Fucoidan is a sulfated polysaccharide that is extracted primarily from seaweed. The polymer contains a natural variation in chemistry based upon the species of seaweed from which it is extracted. We have used two different fucoidans from two different seaweed species (Fucus vesiculosus - FV; and Undaria pinnatifida - UP) as polyanions for the formation of polysaccharide-based polyelectrolyte multilayers (PEMs), to determine if the chemistry of different fucoidans can be chosen to fine-tune the structure of the polymer film. Partially acetylated chitosan was chosen as the polycation for the work, and the presented data illustrate the effect of secondary hydrogen bonding interactions on PEM build-up and properties. Ellipsometry and quartz crystal microbalance with dissipation monitoring (QCM-D) measurements performed during film build-up enabled detailed measurements of layer thickness, adsorbed mass, and the dynamics of the multilayer formation process. High quality atomic force microscopy (AFM) images revealed the differences in morphology of the PEMs formed from the two fucoidans, and allowed for a more direct layer thickness measurement. X-ray photoelectron spectroscopy (XPS) confirmed the chemistry of the films, and an indication of the altered interactions between chitosan and fucoidan with variation in fucoidan type, but also with layer number. Distinct differences were observed between multilayers formed with the two fucoidans, with those constructed using UP having thinner, denser, less hydrated layers than those constructed using FV. These differences are discussed in the context of their varied chemistry, primarily their difference in molecular weight and degree of acetylation. PMID:25599229

  3. Vegetation structure and fire weather influence variation in burn severity and fuel consumption during peatland wildfires

    NASA Astrophysics Data System (ADS)

    Davies, G. M.; Domènech, R.; Gray, A.; Johnson, P. C. D.

    2015-09-01

    Temperate peatland wildfires are of significant environmental concern but information on their environmental effects is lacking. We assessed variation in burn severity and fuel consumption within and between wildfires that burnt British moorlands in 2011 and 2012. We adapted the Composite Burn Index (pCBI) to provide semi-quantitative estimates of burn severity. Pre- and post-fire surface (shrubs and graminoids) and ground (litter, moss, duff) fuel loads associated with large wildfires were assessed using destructive sampling and analysed using a Generalised Linear Mixed Model (GLMM). Consumption during wildfires was compared with published estimates of consumption during prescribed burns. Burn severity and fuel consumption were related to fire weather, assessed using the Canadian Fire Weather Index System (FWI System), and pre-fire fuel structure. pCBI varied 1.6 fold between, and up to 1.7 fold within, wildfires. pCBI was higher where moisture codes of the FWI System indicated drier fuels. Spatial variation in pre- and post-fire fuel load accounted for a substantial proportion of the variance in fuel loads. Average surface fuel consumption was a linear function of pre-fire fuel load. Average ground fuel combustion completeness could be predicted by the Buildup Index. Carbon release ranged between 0.36 and 1.00 kg C m-2. The flammability of ground fuel layers may explain the higher C release-rates seen for wildfires in comparison to prescribed burns. Drier moorland community types appear to be at greater risk of severe burns than blanket-bog communities.

  4. Insights into the genome structure and copy-number variation of Eimeria tenella

    PubMed Central

    2012-01-01

    of the genome of E. tenella from shotgun data, and to help reveal its overall structure. A preliminary assessment of copy-number variation (extra or missing copies of genomic segments) between strains of E. tenella was also carried out. The emerging picture is of a very unusual genome architecture displaying inter-strain copy-number variation. We suggest that these features may be related to the known ability of this parasite to rapidly develop drug resistance. PMID:22889016

  5. A new default restraint library for the protein backbone in Phenix: a conformation-dependent geometry goes mainstream

    PubMed Central

    Moriarty, Nigel W.; Tronrud, Dale E.; Adams, Paul D.; Karplus, P. Andrew

    2016-01-01

    Chemical restraints are a fundamental part of crystallographic protein structure refinement. In response to mounting evidence that conventional restraints have shortcomings, it has previously been documented that using backbone restraints that depend on the protein backbone conformation helps to address these shortcomings and improves the performance of refinements [Moriarty et al. (2014 ▸), FEBS J. 281, 4061–4071]. It is important that these improvements be made available to all in the protein crystallography community. Toward this end, a change in the default geometry library used by Phenix is described here. Tests are presented showing that this change will not generate increased numbers of outliers during validation, or deposition in the Protein Data Bank, during the transition period in which some validation tools still use the conventional restraint libraries. PMID:26894545

  6. Oligo(p-phenylene-ethynylene)s with backbone conformation controlled by competitive intramolecular hydrogen bonds.

    PubMed

    Hu, Wei; Yan, Qifan; Zhao, Dahui

    2011-06-14

    A series of conjugated oligo(p-phenylene-ethynylene) (OPE) molecules with backbone conformations (that is, the relative orientations of the contained phenylene units) controlled by competitive intramolecular hydrogen bonds to be either co-planar or random were synthesised and studied. In these oligomers, carboxylate and amido substituents were attached to alternate phenylene units in the OPE backbone. These functional groups were able to form intramolecular hydrogen bonds between neighbouring phenylene units. Thereby, all phenylene units in the backbone were confined in a co-planar conformation. This planarised structure featured a more extended effective conjugation length than that of regular OPEs with phenylene units adopting random orientation due to a low rotational-energy barrier. However, if a tri(ethylene glycol) (Tg) side chain was appended to the amido group, it enabled another type of intramolecular hydrogen bond, formed by the Tg chain folding back and the contained ether oxygen atom competing with the ester carbonyl group as the hydrogen-bond acceptor. The outcome of this competition was proven to depend on the length of the alkylene linker joining the ether oxygen atom to the amido group. Specifically, if the Tg chain folded back to form a five-membered cyclic structure, this hydrogen-bonding motif was sufficiently robust to overrule the hydrogen bonds between adjacent phenylene units. Consequently, the oligomers assumed non-planar conformations. However, if the side chain formed a six-membered ring by hydrogen bonding with the amido NH group, such a motif was much less stable and yielded in the competition with the ester carbonyl group from the adjacent phenylene unit. Thus, the hydrogen bonds between the phenylene units remained, and the co-planar conformation was manifested. In our system, the hydrogen bonds formed by the back-folded Tg chain and amido NH group relied on a single oxygen atom as the hydrogen-bond acceptor. The additional oxygen

  7. Glycoinositolphospholipids from Leishmania braziliensis and L. infantum: Modulation of Innate Immune System and Variations in Carbohydrate Structure

    PubMed Central

    Assis, Rafael Ramiro; Ibraim, Izabela Coimbra; Noronha, Fátima Soares; Turco, Salvatore Joseph; Soares, Rodrigo Pedro

    2012-01-01

    The essential role of the lipophosphoglycan (LPG) of Leishmania in innate immune response has been extensively reported. However, information about the role of the LPG-related glycoinositolphospholipids (GIPLs) is limited, especially with respect to the New World species of Leishmania. GIPLs are low molecular weight molecules covering the parasite surface and are similar to LPG in sharing a common lipid backbone and a glycan motif containing up to 7 sugars. Critical aspects of their structure and functions are still obscure in the interaction with the vertebrate host. In this study, we evaluated the role of those molecules in two medically important South American species Leishmania infantum and L. braziliensis, causative agents of visceral (VL) and cutaneous Leishmaniasis (CL), respectively. GIPLs derived from both species did not induce NO or TNF-α production by non-primed murine macrophages. Additionally, primed macrophages from mice (BALB/c, C57BL/6, TLR2−/− and TLR4−/−) exposed to GIPLs from both species, with exception to TNF-α, did not produce any of the cytokines analyzed (IL1-β, IL-2, IL-4, IL-5, IL-10, IL-12p40, IFN-γ) or p38 activation. GIPLs induced the production of TNF-α and NO by C57BL/6 mice, primarily via TLR4. Pre incubation of macrophages with GIPLs reduced significantly the amount of NO and IL-12 in the presence of IFN-γ or lipopolysaccharide (LPS), which was more pronounced with L. braziliensis GIPLs. This inhibition was reversed after PI-specific phospholipase C treatment. A structural analysis of the GIPLs showed that L. infantum has manose rich GIPLs, suggestive of type I and Hybrid GIPLs while L. braziliensis has galactose rich GIPLs, suggestive of Type II GIPLs. In conclusion, there are major differences in the structure and composition of GIPLs from L. braziliensis and L. infantum. Also, GIPLs are important inhibitory molecules during the interaction with macrophages. PMID:22389743

  8. Efficient synthesis of longer Aβ peptides via removable backbone modification.

    PubMed

    Zuo, Chao; Tang, Shan; Si, Yan-Yan; Wang, Zhipeng A; Tian, Chang-Lin; Zheng, Ji-Shen

    2016-06-14

    Longer amyloid-beta (Aβ) peptides (43 to 49 amino acids) play essential roles in the pathology of Alzheimer's disease (AD). The difficulty in the preparation of longer Aβ peptides is still an obstacle to elucidate their roles in AD. Herein we report a robust and efficient strategy for the chemical synthesis of longer Aβ peptides (Aβ48 and Aβ49). A key feature of this method is the installation of removable Arg4-tagged backbone modification groups into the hydrophobic region of Aβ. This modification can improve the handling properties of the purification, ligation and mass characterization of longer Aβ peptides. The practicability of the new method has been demonstrated by the successful synthesis of Aβ48 and Aβ49 peptides. PMID:27188564

  9. Transforming plastic surfaces with electrophilic backbones from hydrophobic to hydrophilic.

    PubMed

    Kim, Samuel; Bowen, Raffick A R; Zare, Richard N

    2015-01-28

    We demonstrate a simple nonaqueous reaction scheme for transforming the surface of plastics from hydrophobic to hydrophilic. The chemical modification is achieved by base-catalyzed trans-esterification with polyols. It is permanent, does not release contaminants, and causes no optical or mechanical distortion of the plastic. We present contact angle measurements to show successful modification of several types of plastics including poly(ethylene terephthalate) (PET) and polycarbonate (PC). Its applicability to blood analysis is explored using chemically modified PET blood collection tubes and found to be quite satisfactory. We expect this approach will reduce the cost of manufacturing plastic devices with optimized wettability and can be generalized to other types of plastic materials having an electrophilic linkage as its backbone. PMID:25565370

  10. Elucidating Common Structural Features of Human Pathogenic Variations Using Large-Scale Atomic-Resolution Protein Networks

    PubMed Central

    Das, Jishnu; Lee, Hao Ran; Sagar, Adithya; Fragoza, Robert; Liang, Jin; Wei, Xiaomu; Wang, Xiujuan; Mort, Matthew; Stenson, Peter D.; Cooper, David N.; Yu, Haiyuan

    2016-01-01

    With the rapid growth of structural genomics, numerous protein crystal structures have become available. However, the parallel increase in knowledge of the functional principles underlying biological processes, and more specifically the underlying molecular mechanisms of disease, has been less dramatic. This notwithstanding, the study of complex cellular networks has made possible the inference of protein functions on a large scale. Here, we combine the scale of network systems biology with the resolution of traditional structural biology to generate a large-scale atomic-resolution interactome-network comprising 3,398 interactions between 2,890 proteins with a well-defined interaction interface and interface residues for each interaction. Within the framework of this atomic-resolution network, we have explored the structural principles underlying variations causing human-inherited disease. We find that in-frame pathogenic variations are enriched at both the interface and in the interacting domain, suggesting that variations not only at interface “hot-spots,” but in the entire interacting domain can result in alterations of interactions. Further, the sites of pathogenic variations are closely related to the biophysical strength of the interactions they perturb. Finally, we show that biochemical alterations consequent to these variations are considerably more disruptive than evolutionary changes, with the most significant alterations at the protein interaction interface. PMID:24599843

  11. Genetic Variation and Structure in Contrasting Geographic Distributions: Widespread Versus Restricted Black-Tailed Prairie Dogs (Subgenus Cynomys).

    PubMed

    Castellanos-Morales, Gabriela; Ortega, Jorge; Castillo-Gámez, Reyna A; Sackett, Loren C; Eguiarte, Luis E

    2015-01-01

    Species of restricted distribution are considered more vulnerable to extinction because of low levels of genetic variation relative to widespread taxa. Species of the subgenus Cynomys are an excellent system to compare genetic variation and degree of genetic structure in contrasting geographic distributions. We assessed levels of genetic variation, genetic structure, and genetic differentiation in widespread Cynomys ludovicianus and restricted C. mexicanus using 1997bp from the cytochrome b and control region (n = 223 C. ludovicianus; 77 C. mexicanus), and 10 nuclear microsatellite loci (n = 207 and 78, respectively). Genetic variation for both species was high, and genetic structure in the widespread species was higher than in the restricted species. C. mexicanus showed values of genetic variation, genetic structure, and genetic differentiation similar to C. ludovicianus at smaller geographic scales. Results suggest the presence of at least 2 historical refuges for C. ludovicianus and that the Sierra Madre Occidental represents a barrier to gene flow. Chihuahua and New Mexico possess high levels of genetic diversity and should be protected, while Sonora should be treated as an independent management unit. For C. mexicanus, connectivity among colonies is very important and habitat fragmentation and habitat loss should be mitigated to maintain gene flow. PMID:26245783

  12. Uncovering the origins of spiral structure through the measurement of pattern speeds and their radial variation

    NASA Astrophysics Data System (ADS)

    Meidt, Sharon E.

    At the intersection of galactic dynamics, evolution and global structure, unresolved issues in the nature and origin of spirals can be addressed through the characterization of the angular speeds of the patterns and their possible radial variation. In this thesis I describe the development, testing, and application of the Radial Tremaine-Weinberg (TWR) Method, a generalized version of the continuity-based TW method wherein the pattern speed is allowed to vary arbitrarily with radius. I will address the utility of, and caveats in applying, the TWR calculation together with a standard regularization technique in a series of tests on N- body simulations. The regularization, which smooths otherwise intrinsically noisy solutions based on a priori assumptions for the radial dependence of the pattern speed, proves to be essential for achieving the radial precision necessary for accurate measurement. I also present results from applications of the TWR method to observations of real galaxies, where the possible sources and sinks in the continuity equation are well understood. Using CO observations of the grand design galaxy M51, the TWR method reveals a heretofore un-measured inner spiral pattern speed for the bright two-armed spiral structure, with a value significantly higher than conventional estimates. In addition, the radial dependence implied in the TWR solution suggests a possible resonant link between the inner and outer regions of the bright spiral arms. These findings signify an advance in observational investigations into the nature and origin of grand-design spiral structure. By analyzing high-quality HI and CO data cubes available for four other spiral galaxies, the characteristic signatures of the processes that drive spiral structure are likewise identifiable; within this small sample, the first direct evidence for the presence of resonant coupling of multiple distinct patterns is found in some galaxies, while a simple single pattern speed is measured in

  13. Structural variation along the southwestern Nankai seismogenic zone related to various earthquake phenomena

    NASA Astrophysics Data System (ADS)

    Nakanishi, A.; Shimomura, N.; Kodaira, S.; Obana, K.; Takahashi, T.; Yamamoto, Y.; Sato, T.; Kashiwase, K.; Fujimori, H.; Kaneda, Y.; Mochizuki, K.; Kato, A.; Iidaka, T.; Kurashimo, E.; Shinohara, M.; Takeda, T.; Shiomi, K.

    2011-12-01

    In the Nankai Trough subduction seismogenic zone, the Nankai and Tonankai earthquakes had often occurred simultaneously, and caused a great event. In order to reduce a great deal of damage to coastal area from both strong ground motion and tsunami generation, it is necessary to understand rupture synchronization and segmentation of the Nankai megathrust earthquake. For a precise estimate of the rupture area of the Nankai megathrust event, it is important to know the geometry of the subducting Philippine Sea plate and deep subduction structure along the Nankai Trough. To obtain the deep subduction structure of the coseismic rupture area of the Nankai earthquake in 1946 off Shikoku area, the large-scale high-resolution wide-angle seismic study was conducted in 2009 and 2010. In this study, 201 and 200 ocean bottom seismographs were deployed off the Shikoku Island and the Kii channel respectively. A tuned airgun system (7800 cu. in.) shot every 200m along 13 profiles. Airgun shots were also recorded along an onshore seismic profile (prepared by ERI, univ. of Tokyo and NIED) prolonged from the offshore profile off the Kii Peninsula. Long-term observation was conducted for ~9 months by 21 OBSs off the Shikoku area and 20 OBSs off the Kii channel.This research is part of 'Research concerning Interaction Between the Tokai, Tonankai and Nankai Earthquakes' funded by Ministry of Education, Culture, Sports, Science and Technology, Japan. Structural images of the overriding plate indicate the old accreted sediments (the Cretaceous-Tertiary accretionary prism) with the velocity greater than 6km/s extend seaward from off the Shikoku to the Hyuga-nada. Moreover, the young accreted sediments become relatively thinner eastward from off the cape Ashizuri to Muroto. These structural variations might be related to the different rupture pattern of the Nankai event. Structural image of the deep low frequency earthquakes and tremors is shown by using the airgun shots recorded at onshore

  14. Lack of Structural Variation but Extensive Length Polymorphisms and Heteroplasmic Length Variations in the Mitochondrial DNA Control Region of Highly Inbred Crested Ibis, Nipponia nippon.

    PubMed

    He, Xue-Lian; Ding, Chang-Qing; Han, Jian-Lin

    2013-01-01

    The animal mitochondrial DNA (mtDNA) length polymorphism and heteroplasmy are accepted to be universal. Here we report the lack of structural variation but the presence of length polymorphism as well as heteroplasmy in mtDNA control region of an endangered avian species - the Crested Ibis (Nipponia nippon). The complete control region was directly sequenced while the distribution pattern and inheritance of the length variations were examined using both direct sequencing and genotyping of the PCR fragments from captive birds with pedigrees, wild birds and a historical specimen. Our results demonstrated that there was no structural variation in the control region, however, different numbers of short tandem repeats with an identical motif of CA3CA2CA3 at the 3'-end of the control region determined the length polymorphisms among and heteroplasmy within individual birds. There were one to three predominant fragments in every bird; nevertheless multiple minor fragments coexist in all birds. These extremely high polymorphisms were suggested to have derived from the 'replication slippage' of a perfect microsatellite evolution following the step-wise mutational model. The patterns of heteroplasmy were found to be shifted between generations and among siblings but rather stable between blood and feather samples. This study provides the first evidence of a very extensive mtDNA length polymorphism and heteroplasmy in the highly inbred Crested Ibis which carries an mtDNA genome lack of structural genetic diversity. The analysis of pedigreed samples also sheds light on the transmission of mtDNA length heteroplasmy in birds following the genetic bottleneck theory. Further research focusing on the generation and transmission of particular mtDNA heteroplasmy patterns in single germ line of Crested Ibis is encouraged by this study. PMID:23805212

  15. Lack of Structural Variation but Extensive Length Polymorphisms and Heteroplasmic Length Variations in the Mitochondrial DNA Control Region of Highly Inbred Crested Ibis, Nipponia nippon

    PubMed Central

    He, Xue-Lian; Ding, Chang-Qing; Han, Jian-Lin

    2013-01-01

    The animal mitochondrial DNA (mtDNA) length polymorphism and heteroplasmy are accepted to be universal. Here we report the lack of structural variation but the presence of length polymorphism as well as heteroplasmy in mtDNA control region of an endangered avian species – the Crested Ibis (Nipponia nippon). The complete control region was directly sequenced while the distribution pattern and inheritance of the length variations were examined using both direct sequencing and genotyping of the PCR fragments from captive birds with pedigrees, wild birds and a historical specimen. Our results demonstrated that there was no structural variation in the control region, however, different numbers of short tandem repeats with an identical motif of CA3CA2CA3 at the 3′-end of the control region determined the length polymorphisms among and heteroplasmy within individual birds. There were one to three predominant fragments in every bird; nevertheless multiple minor fragments coexist in all birds. These extremely high polymorphisms were suggested to have derived from the ‘replication slippage’ of a perfect microsatellite evolution following the step-wise mutational model. The patterns of heteroplasmy were found to be shifted between generations and among siblings but rather stable between blood and feather samples. This study provides the first evidence of a very extensive mtDNA length polymorphism and heteroplasmy in the highly inbred Crested Ibis which carries an mtDNA genome lack of structural genetic diversity. The analysis of pedigreed samples also sheds light on the transmission of mtDNA length heteroplasmy in birds following the genetic bottleneck theory. Further research focusing on the generation and transmission of particular mtDNA heteroplasmy patterns in single germ line of Crested Ibis is encouraged by this study. PMID:23805212

  16. Reduced dimensionality (4,3)D-hnCOCANH experiment: an efficient backbone assignment tool for NMR studies of proteins.

    PubMed

    Kumar, Dinesh

    2013-09-01

    Sequence specific resonance assignment of proteins forms the basis for variety of structural and functional proteomics studies by NMR. In this context, an efficient standalone method for rapid assignment of backbone ((1)H, (15)N, (13)C(α) and (13)C') resonances of proteins has been presented here. Compared to currently available strategies used for the purpose, the method employs only a single reduced dimensionality experiment--(4,3)D-hnCOCANH and exploits the linear combinations of backbone ((13)C(α) and (13)C') chemical shifts to achieve a dispersion relatively better compared to those of individual chemical shifts (see the text). The resulted increased dispersion of peaks--which is different in sum (CA + CO) and difference (CA - CO) frequency regions--greatly facilitates the analysis of the spectrum by resolving the problems (associated with routine assignment strategies) arising because of degenerate amide (15)N and backbone (13)C chemical shifts. Further, the spectrum provides direct distinction between intra- and inter-residue correlations because of their opposite peak signs. The other beneficial feature of the spectrum is that it provides: (a) multiple unidirectional sequential (i→i + 1) (15)N and (13)C correlations and (b) facile identification of certain specific triplet sequences which serve as check points for mapping the stretches of sequentially connected HSQC cross peaks on to the primary sequence for assigning the resonances sequence specifically. On top of all this, the F₂-F₃ planes of the spectrum corresponding to sum (CA + CO) and difference (CA - CO) chemical shifts enable rapid and unambiguous identification of sequential HSQC peaks through matching their coordinates in these two planes (see the text). Overall, the experiment presented here will serve as an important backbone assignment tool for variety of structural and functional proteomics and drug discovery research programs by NMR involving well behaved small folded proteins (MW

  17. Seasonal variations in phytoplankton community structure in the Sanggou, Ailian, and Lidao Bays

    NASA Astrophysics Data System (ADS)

    Yuan, Mingli; Zhang, Cuixia; Jiang, Zengjie; Guo, Shujin; Sun, Jun

    2014-12-01

    The seasonal variations in phytoplankton community structure were investigated for the Sanggou Bay (SGB) and the adjacent Ailian Bay (ALB) and Lidao Bay (LDB) in Shandong Peninsula, eastern China. The species composition and cell abundance of phytoplankton in the bay waters in spring (April 2011), summer (August 2011), autumn (October 2011), and winter (January 2012) were examined using the Utermöhl method. A total of 80 taxa of phytoplankton that belong to 39 genera of 3 phyla were identified. These included 64 species of 30 genera in the Phylum Bacillariophyta, 13 species of 8 genera in the Phylum Dinophyta, and 3 species of 1 genus in the Phylum Chrysophyta. During the four seasons, the number of phytoplankton species (43) was the highest in spring, followed by summer and autumn (40), and the lowest number of phytoplankton species (35) was found in winter. Diatoms, especially Paralia sulcata (Ehrenberg) Cleve and Coscinodiscus oculus-iridis Ehrenberg, were predominant in the phytoplankton community throughout the study period, whereas the dominance of dinoflagellate appeared in summer only. The maximum cell abundance of phytoplankton was detected in summer (average 8.08 × 103 cells L-1) whereas their minimum abundance was found in autumn (average 2.60 × 103 cells L-1). The phytoplankton abundance was generally higher in the outer bay than in the inner bay in spring and autumn. In summer, the phytoplankton cells were mainly concentrated in the south of inner SGB, with peak abundance observed along the western coast. In winter, the distribution of phytoplankton cells showed 3 patches, with peak abundance along the western coast as well. On seasonal average, the Shannon-Wiener diversity indices of phytoplankton community ranged from 1.17 to 1.78 (autumn > summer > spring > winter), and the Pielou's evenness indices of phytoplankton ranged from 0.45 to 0.65 (autumn > spring > summer > winter). According to the results of canonical correspondence analysis

  18. Spatial variation of the scaling structure of short-term rainfall over Portugal

    NASA Astrophysics Data System (ADS)

    de Lima, M. I. P.; Coelho, M. F. E. S.; de Lima, J. L. M. P.

    2009-04-01

    The spatial and temporal structure of rain, which typically exhibits extreme variability, is a core issue in studies that span a variety of research areas, e.g. hydrology, hydraulics, environment, energy, economics, society. The interest in rain can demand its study and characterization at a variety of space- and time-scales. Different tools and methodologies are used for this purpose, which are usually complementary. Mainland Portugal is located in the transitional region between the sub-tropical anticyclone and the sub-polar depression zones. The spatial distribution of precipitation over the territory and its seasonal variability are due to the characteristics of the global circulation. One specific feature is the Atlantic origin of many synoptic disturbances, e.g. seasonal movements of the Azores high pressure system, in the context of the regional geography (e.g. latitude, orography, oceanic and continental influences). Although the variation in climate factors is fairly small, it is sufficient to justify significant variations in precipitation. Compared with the northern region of Portugal, the southern region is warmer and drier; there the climate is semi-arid, and the region is well-known for its vulnerability to climate variability. Two storm types dominate the occurrence of rainfall in mainland Portugal: convective storms and frontal storms. Convective storms are typical during the summer and in early and mid autumn, and are more frequent in the southern regions; frontal storms occur principally in the winter season, and affect the northern regions more. In this work we discuss results of scale-invariant analyses of the temporal structure of rain from several locations in mainland Portugal. The aim was to investigate the statistical signature of rain events of different origins, resulting from the large number of mechanisms and factors affecting the rainfall climate over Portugal. The study uses hourly rainfall time series covering periods of about 30

  19. Variations in soil microbial community structure induced by the conversion from paddy fields to upland fields

    NASA Astrophysics Data System (ADS)

    Dai, X.

    2015-12-01

    Land-use conversion is an important factor influencing the carbon and nitrogen gas exchange between land and atmosphere, and soil microorganisms is main driver of soil carbon and nitrogen gas production. Understanding the effect of land-use conversion on soil microbial communities and its influencing factor is important for greenhouse gas emission reduction and soil organic carbon and nitrogen sequestration and stability. The influence of land use conversion on soil process was undergoing a dynamic change, but little research has been done to understand the effect on soil microbial communities during the initial years after land conversion. In the study, the influences of land-use conversion from double rice cropping (RR) to maize-maize (MM) and soybean-peanut (SP) double cropping systems on soil physical and chemical properties, and microbial community structure was studied after two years of the conversion in southern China. The results showed that land use conversion significantly changed soil properties, microbial communities and biomass. Soil pH significantly decreased by 0.50 and 0.52 after conversion to MM and SP, respectively. Soil TN and NH4-N also significantly decreased by 9%-15% and 60% after conversion to upland fields, respectively. The total PLFAs, bacterial, gram-positive bacterial (G+), gram-negative bacterial (G-) and actinomycetic PLFAs decreased significantly. The ng g-1 soil concentration of monounsaturated chain PLFAs 16:1ω7c and 18:1ω9t were significantly higher at paddy fields than at upland fields. No significant differences in soil properties, microbial communities and biomass were found between conversed MM and SP. Our results indicated that land use conversion, not crop type conversed had a significant effects on soil properties and microbial communities at the initial of land conversion. And soil pH was the key factor regulating the variations in soil microbial community structure after land use conversion from paddy to upland fields.

  20. Variations in the abundance of fisheries resources and ecosystem structure in the Japan/East Sea

    NASA Astrophysics Data System (ADS)

    Zhang, Chang Ik; Lee, Jae Bong; Seo, Young Il; Yoon, Sang Cheol; Kim, Suam

    2004-05-01

    Evidence supports the hypothesis that two climatic regime shifts in the North Pacific and the Japan/East Sea, have affected the dynamics of the marine ecosystem and fisheries resources from 1960 to 2000. Changes in both mixed layer depth (MLD) and primary production were detected in the Japan/East Sea after 1976. The 1976 regime shift appears to have caused the biomass replacement with changes in catch production of major exploited fisheries resources, including Pacific saury, Pacific sardine and filefish. Both fisheries yield and fish distribution are reflected in these decadal fluctuations. In the 1960s and 1990s, common squid dominated the catches whereas in the 1970s and 1980s, it was replaced by walleye pollock. In the post-1988 regime shift, the distribution of horse mackerel shifted westward and southward and its distributional overlap with common mackerel decreased. The habitat of Pacific sardine also shifted away from mackerel habitats during this period. To evaluate changes in the organization and structure of the ecosystem in the Japan/East Sea, a mass-balanced model, Ecopath, was employed. Based on two mass-balanced models, representing before (1970-75) and after (1978-84) the 1976 regime shift, the weighted mean trophic level of catch increased from 3.09 before to 3.28 after. Total biomass of species groups in the Japan/East Sea ecosystem increased by 15% and total catch production increased by 48% due to the 1976 regime shift. The largest changes occurred at mid-trophic levels, occupied by fishes and cephalopods. The dominant predatory species shifted from cephalopods to walleye pollock due to the 1976 regime shift. It is concluded that the climatic regime shifts caused changes in the structure of the ecosystem and the roles of major species, as well as, large variations in biomass and production of fisheries resources.

  1. Observations and modeling of the crustal structure and Moho strength variation along the Lesser Antilles Arc

    NASA Astrophysics Data System (ADS)

    Schlaphorst, D.; Kendall, J. M.; Blundy, J. D.; Melekhova, E.; Baptie, B.; Latchman, J. L.; Bouin, M. P.; Tait, S.

    2014-12-01

    Subduction processes influence the crustal structure in their vicinity. The Mohorovičić discontinuity (Moho), separating the crust from the mantle, can be influenced both in its depth and strength. Normally it is stronger than any crustal discontinuity, but a change in subducted material can weaken the Moho. We are investigating the change in crustal structure along the Lesser Antilles Arc using three component broadband stations on various islands along the arc. This arc is formed by the slow subduction (~2cm/yr) of the North and South American plates beneath the Caribbean plate. We are using receiver functions and H-κ stacking to constrain the depth (H) of the strongest discontinuity and the average crustal P-to-S wave velocity ratio (κ) to that depth. The ratio constrains the subsurface material. Results in this field of study can easily be ground-truthed with the composition of materials found in samples from the same area to find uniform patterns. Our results show significant depth variations of the discontinuity. Some of our results match the depth of an inter-crustal boundary (Conrad) found in a previous study (Boynton, 1979, GJRAS). This suggests a comparably weak Moho in these areas, a theory that is supported by models based on petrological results. We compare our results to synthetic data from inversion models that determine the depth location of the Conrad and the Moho. For this purpose we use a combined method of different inversion approaches and include petrological constraints. Where we previously see agreement between the depth of the Conrad in Boynton's study and the H-κ stacking, the models now confirm this result.

  2. BCS-BEC crossover and phase structure of relativistic systems: A variational approach

    SciTech Connect

    Chatterjee, Bhaswar; Mishra, Hiranmaya; Mishra, Amruta

    2009-01-01

    We investigate here the BCS-BEC crossover in relativistic systems using a variational construct for the ground state and the minimization of the thermodynamic potential. This is first studied in a four-fermion point interaction model and with a BCS type ansatz for the ground state with fermion pairs. It is shown that the antiparticle degrees of freedom play an important role in the BCS-BEC crossover physics, even when the ratio of Fermi momentum to the mass of the fermion is small. We also consider the phase structure for the case of fermion pairing with imbalanced populations. Within the ansatz, thermodynamically stable gapless modes for both fermions and antifermions are seen for strong coupling in the Bose-Einstein condensation (BEC) regime. We further investigate the effect of fluctuations of the condensate field by treating it as a dynamical field and generalize the BCS ansatz to include quanta of the condensate field also in a boson-fermion model with quartic self-interaction of the condensate field. It is seen that the critical temperature decreases with inclusion of fluctuations.

  3. Variations in the Structure of the Prelunate Gyrus in Old World Monkeys

    PubMed Central

    Van der Gucht, Estel; Youakim, Michele; Arckens, Lutgarde; Hof, Patrick R.; Baizer, Joan S.

    2010-01-01

    Anatomical and electrophysiological studies have revealed a complex organization in the macaque prelunate gyrus. We investigated the morphology and architecture of the prelunate gyrus in Old World monkeys. In Macaca nemestrina, we observed a sulcus crossing the prelunate gyrus within 2 mm of the vertical meridian representation. In other macaque species and other cercopithecines, we observed substantial variations in sulcal morphology across the prelunate gyrus. We did not find a sulcus in all species, and the location and depth of that indentation on the gyrus varied among species. A deep sulcus was observed in all species that emerged earlier in evolution than macaques, like guenons, baboons, and colobines. We analyzed the regional and parcellation features of the prelunate gyrus in three macaque species, M. maura, M. mulatta and M. radiata, and in Erythrocebus patas, with emphasis on the relation of structure to the distribution of prelunate visual areas. Nonphosphorylated neurofilament protein immunoreactivity permitted the delineation of a novel area in the prelunate gyrus of Old World monkeys, located around the prelunate sulcus. Species-specific patterns were also observed in the prelunate gyrus of the patas monkey, compared to macaques. These observations, as well as a cladistic analysis of the data, suggest an expanded and diversified organization of the prelunate gyrus in some cercopithecoids that may reflect adaptation to specific ecological environments. It was however progressively lost in most macaques, being retained only in species that diverged early in the evolution of the genus Macaca, such as M. nemestrina and M. maura. PMID:16779809

  4. Structure and temporal variation of the phytoplankton of a macrotidal beach from the Amazon coastal zone.

    PubMed

    Matos, Jislene B; Oliveira, Suellen M O DE; Pereira, Luci C C; Costa, Rauquírio M DA

    2016-09-01

    The present study aimed to analyze the structure and the temporal variation of the phytoplankton of Ajuruteua beach (Bragança, Pará) and to investigate the influence of environmental variables on the dynamics of this community to provide a basis about the trophic state of this environment. Biological, hydrological and hydrodynamic samplings were performed during a nyctemeral cycle in the months of November/08, March/09, June/09 and September/09. We identified 110 taxa, which were distributed among the diatoms (87.3%), dinoflagellates (11.8%) and cyanobacteria (0.9%), with the predominance of neritic species, followed by the tychoplankton species. Chlorophyll-a concentrations were the highest during the rainy period (24.5 mg m-3), whereas total phytoplankton density was higher in the dry period (1,255 x 103 cell L-1). However, phytoflagellates density was significantly higher during the rainy period. Cluster Analysis revealed the formation of four groups, which were influenced by the monthly differences in the environmental variables. The Principal Component Analysis indicated salinity and chlorophyll-a as the main variables that explained the components. Spearman correlation analysis supported the influence of these variables on the local phytoplankton community. Overall, the results obtained suggest that rainfall and strong local hydrodynamics play an important role in the dynamic of the phytoplankton of Ajuruteua beach, by influencing both environmental and biological variables. PMID:27627065

  5. COSMOS: accurate detection of somatic structural variations through asymmetric comparison between tumor and normal samples

    PubMed Central

    Yamagata, Koichi; Yamanishi, Ayako; Kokubu, Chikara; Takeda, Junji; Sese, Jun

    2016-01-01

    An important challenge in cancer genomics is precise detection of structural variations (SVs) by high-throughput short-read sequencing, which is hampered by the high false discovery rates of existing analysis tools. Here, we propose an accurate SV detection method named COSMOS, which compares the statistics of the mapped read pairs in tumor samples with isogenic normal control samples in a distinct asymmetric manner. COSMOS also prioritizes the candidate SVs using strand-specific read-depth information. Performance tests on modeled tumor genomes revealed that COSMOS outperformed existing methods in terms of F-measure. We also applied COSMOS to an experimental mouse cell-based model, in which SVs were induced by genome engineering and gamma-ray irradiation, followed by polymerase chain reaction-based confirmation. The precision of COSMOS was 84.5%, while the next best existing method was 70.4%. Moreover, the sensitivity of COSMOS was the highest, indicating that COSMOS has great potential for cancer genome analysis. PMID:26833260

  6. Structural variation discovery in the cancer genome using next generation sequencing: computational solutions and perspectives.

    PubMed

    Liu, Biao; Conroy, Jeffrey M; Morrison, Carl D; Odunsi, Adekunle O; Qin, Maochun; Wei, Lei; Trump, Donald L; Johnson, Candace S; Liu, Song; Wang, Jianmin

    2015-03-20

    Somatic Structural Variations (SVs) are a complex collection of chromosomal mutations that could directly contribute to carcinogenesis. Next Generation Sequencing (NGS) technology has emerged as the primary means of interrogating the SVs of the cancer genome in recent investigations. Sophisticated computational methods are required to accurately identify the SV events and delineate their breakpoints from the massive amounts of reads generated by a NGS experiment. In this review, we provide an overview of current analytic tools used for SV detection in NGS-based cancer studies. We summarize the features of common SV groups and the primary types of NGS signatures that can be used in SV detection methods. We discuss the principles and key similarities and differences of existing computational programs and comment on unresolved issues related to this research field. The aim of this article is to provide a practical guide of relevant concepts, computational methods, software tools and important factors for analyzing and interpreting NGS data for the detection of SVs in the cancer genome. PMID:25849937

  7. A fast variational Gaussian wavepacket method: size-induced structural transitions in large neon clusters.

    PubMed

    Georgescu, Ionuţ; Mandelshtam, Vladimir A

    2011-10-21

    The variational Gaussian wavepacket (VGW) approximation provides an alternative to path integral Monte Carlo for the computation of thermodynamic properties of many-body systems at thermal equilibrium. It provides a direct access to the thermal density matrix and is particularly efficient for Monte Carlo approaches, as for an N-body system it operates in a non-inflated 3N-dimensional configuration space. Here, we greatly accelerate the VGW method by retaining only the relevant short-range correlations in the (otherwise full) 3N × 3N Gaussian width matrix without sacrificing the accuracy of the fully coupled VGW method. This results in the reduction of the original O(N(3)) scaling to O(N(2)). The fast-VGW method is then applied to quantum Lennard-Jones clusters with sizes up to N = 6500 atoms. Following Doye and Calvo [JCP 116, 8307 (2002)] we study the competition between the icosahedral and decahedral structural motifs in Ne(N) clusters as a function of N. PMID:22029296

  8. Metropolitan Structure and Neighborhood Attainment: Exploring Intermetropolitan Variation in Racial Residential Segregation

    PubMed Central

    South, Scott J.; Crowder, Kyle; Pais, Jeremy

    2011-01-01

    Using data from the 1981, 1991, and 2001 waves of the Panel Study of Income Dynamics and several decennial censuses, we examine how characteristics of metropolitan areas are associated with black and white households’ neighborhood racial composition. Results from hierarchical linear models show that about 20% to 40% of the variation in the percentage of households’ tract population that is non-Hispanic white or non-Hispanic black exists across metropolitan areas. Over time, white households’ exposure to non-Hispanic white neighbors has declined, and their exposure to non-Hispanic black neighbors has increased; the reverse trends are observed for blacks. These trends cannot be attributed to changes in the ecological structure of metropolitan areas. Blacks have fewer white neighbors in large metropolitan areas containing sizable minority populations, and blacks have more white neighbors in metropolitan areas with high government employment. Whites have more black neighbors in metropolitan areas with high levels of government employment and ample new housing; whites have fewer black neighbors in metropolitan areas with a high level of municipal fragmentation. The association between metropolitan-area percentage black and tract percentage black is weaker among whites than among blacks, suggesting that whites are especially motivated to self-segregate in metropolitan areas with large black populations. PMID:21863366

  9. Transposon Insertions, Structural Variations, and SNPs Contribute to the Evolution of the Melon Genome.

    PubMed

    Sanseverino, Walter; Hénaff, Elizabeth; Vives, Cristina; Pinosio, Sara; Burgos-Paz, William; Morgante, Michele; Ramos-Onsins, Sebastián E; Garcia-Mas, Jordi; Casacuberta, Josep Maria

    2015-10-01

    The availability of extensive databases of crop genome sequences should allow analysis of crop variability at an unprecedented scale, which should have an important impact in plant breeding. However, up to now the analysis of genetic variability at the whole-genome scale has been mainly restricted to single nucleotide polymorphisms (SNPs). This is a strong limitation as structural variation (SV) and transposon insertion polymorphisms are frequent in plant species and have had an important mutational role in crop domestication and breeding. Here, we present the first comprehensive analysis of melon genetic diversity, which includes a detailed analysis of SNPs, SV, and transposon insertion polymorphisms. The variability found among seven melon varieties representing the species diversity and including wild accessions and highly breed lines, is relatively high due in part to the marked divergence of some lineages. The diversity is distributed nonuniformly across the genome, being lower at the extremes of the chromosomes and higher in the pericentromeric regions, which is compatible with the effect of purifying selection and recombination forces over functional regions. Additionally, this variability is greatly reduced among elite varieties, probably due to selection during breeding. We have found some chromosomal regions showing a high differentiation of the elite varieties versus the rest, which could be considered as strongly selected candidate regions. Our data also suggest that transposons and SV may be at the origin of an important fraction of the variability in melon, which highlights the importance of analyzing all types of genetic variability to understand crop genome evolution. PMID:26174143

  10. BreaKmer: detection of structural variation in targeted massively parallel sequencing data using kmers

    PubMed Central

    Abo, Ryan P.; Ducar, Matthew; Garcia, Elizabeth P.; Thorner, Aaron R.; Rojas-Rudilla, Vanesa; Lin, Ling; Sholl, Lynette M.; Hahn, William C.; Meyerson, Matthew; Lindeman, Neal I.; Van Hummelen, Paul; MacConaill, Laura E.

    2015-01-01

    Genomic structural variation (SV), a common hallmark of cancer, has important predictive and therapeutic implications. However, accurately detecting SV using high-throughput sequencing data remains challenging, especially for ‘targeted’ resequencing efforts. This is critically important in the clinical setting where targeted resequencing is frequently being applied to rapidly assess clinically actionable mutations in tumor biopsies in a cost-effective manner. We present BreaKmer, a novel approach that uses a ‘kmer’ strategy to assemble misaligned sequence reads for predicting insertions, deletions, inversions, tandem duplications and translocations at base-pair resolution in targeted resequencing data. Variants are predicted by realigning an assembled consensus sequence created from sequence reads that were abnormally aligned to the reference genome. Using targeted resequencing data from tumor specimens with orthogonally validated SV, non-tumor samples and whole-genome sequencing data, BreaKmer had a 97.4% overall sensitivity for known events and predicted 17 positively validated, novel variants. Relative to four publically available algorithms, BreaKmer detected SV with increased sensitivity and limited calls in non-tumor samples, key features for variant analysis of tumor specimens in both the clinical and research settings. PMID:25428359

  11. Structural variation discovery in the cancer genome using next generation sequencing: Computational solutions and perspectives

    PubMed Central

    Liu, Biao; Conroy, Jeffrey M.; Morrison, Carl D.; Odunsi, Adekunle O.; Qin, Maochun; Wei, Lei; Trump, Donald L.; Johnson, Candace S.; Liu, Song; Wang, Jianmin

    2015-01-01

    Somatic Structural Variations (SVs) are a complex collection of chromosomal mutations that could directly contribute to carcinogenesis. Next Generation Sequencing (NGS) technology has emerged as the primary means of interrogating the SVs of the cancer genome in recent investigations. Sophisticated computational methods are required to accurately identify the SV events and delineate their breakpoints from the massive amounts of reads generated by a NGS experiment. In this review, we provide an overview of current analytic tools used for SV detection in NGS-based cancer studies. We summarize the features of common SV groups and the primary types of NGS signatures that can be used in SV detection methods. We discuss the principles and key similarities and differences of existing computational programs and comment on unresolved issues related to this research field. The aim of this article is to provide a practical guide of relevant concepts, computational methods, software tools and important factors for analyzing and interpreting NGS data for the detection of SVs in the cancer genome. PMID:25849937

  12. The Oklo bound on the time variation of the fine-structure constant revisited

    NASA Astrophysics Data System (ADS)

    Damour, Thibault; Dyson, Freeman

    1996-02-01

    It has been pointed out by Shlyakhter that data from the natural fission reactors which operated about two billion years ago at Oklo (Gabon) had the potential of providing an extremely tight bound on the variability of the fine-structure constant α. We revisit the derivation of such a bound by (i) reanalyzing a large selection of published rare-earth data from Oklo, (ii) critically taking into account the very large uncertainty of the temperature at which the reactors operated, and (iii) connecting in a new way (using isotope shift measurements) the Oklo-derived constraint on a possible shift of thermal neutron-capture resonances with a bound on the time variation of α. Our final (95% C.L.) results are: -0.9 × 10 -7 < ( αOklo - αnow)/ α < 1.2 × 10 -7 and -6.7 × 10 -17yr-1 < αdotaveraged/α < 5.0 × 10 -17yr-1.

  13. Microsatellite variation and genetic structuring in Mugil liza (Teleostei: Mugilidae) populations from Argentina and Brazil

    NASA Astrophysics Data System (ADS)

    Mai, Ana C. G.; Miño, Carolina I.; Marins, Luis F. F.; Monteiro-Neto, Cassiano; Miranda, Laura; Schwingel, Paulo R.; Lemos, Valéria M.; Gonzalez-Castro, Mariano; Castello, Jorge P.; Vieira, João P.

    2014-08-01

    The mullet Mugil liza is distributed along the Atlantic coast of South America, from Argentina to Venezuela, and it is heavily exploited in Brazil. We assessed patterns of distribution of neutral nuclear genetic variation in 250 samples from the Brazilian states of Rio de Janeiro, São Paulo, Santa Catarina and Rio Grande do Sul (latitudinal range of 23-31°S) and from Buenos Aires Province in Argentina (36°S). Nine microsatellite loci revealed 131 total alleles, 3-23 alleles per locus, He: 0.69 and Ho: 0.67. Significant genetic differentiation was observed between Rio de Janeiro samples (23°S) and those from all other locations, as indicated by FST, hierarchical analyses of genetic structure, Bayesian cluster analyses and assignment tests. The presence of two different demographic clusters better explains the allelic diversity observed in mullets from the southernmost portion of the Atlantic coast of Brazil and from Argentina. This may be taken into account when designing fisheries management plans involving Brazilian, Uruguayan and Argentinean M. liza populations.

  14. Structural variation and missense mutation in SBDS associated with Shwachman-Diamond syndrome

    PubMed Central

    2014-01-01

    Background Shwachman–Diamond syndrome (SDS) is an autosomal recessive ribosomopathy caused mainly by compound heterozygous mutations in SBDS. Structural variation (SV) involving the SBDS locus has been rarely reported in association with the disease. We aimed to determine whether an SV contributed to the pathogenesis of a case lacking biallelic SBDS point mutations. Case presentation Whole exome sequencing was performed in a patient with SDS lacking biallelic SBDS point mutations. Array comparative genomic hybridization and Southern blotting were used to seek SVs across the SBDS locus. Locus-specific polymerase chain reaction (PCR) encompassing flanking intronic sequence was also performed to investigate mutation within the locus. RNA expression and Western blotting were performed to analyze allele and protein expression. We found the child harbored a single missense mutation in SBDS (c.98A > C; p.K33T), inherited from the mother, and an SV in the SBDS locus, inherited from the father. The missense allele and SV segregated in accordance with Mendelian expectations for autosomal recessive SDS. Complementary DNA and western blotting analysis and locus specific PCR support the contention that the SV perturbed SBDS protein expression in the father and child. Conclusion Our findings implicate genomic rearrangements in the pathogenesis of some cases of SDS and support patients lacking biallelic SBDS point mutations be tested for SV within the SBDS locus. PMID:24898207

  15. Transcription-coupled genetic instability marks acute lymphoblastic leukemia structural variation hotspots

    PubMed Central

    Heinäniemi, Merja; Vuorenmaa, Tapio; Teppo, Susanna; Kaikkonen, Minna U; Bouvy-Liivrand, Maria; Mehtonen, Juha; Niskanen, Henri; Zachariadis, Vasilios; Laukkanen, Saara; Liuksiala, Thomas; Teittinen, Kaisa; Lohi, Olli

    2016-01-01

    Progression of malignancy to overt disease requires multiple genetic hits. Activation-induced deaminase (AID) can drive lymphomagenesis by generating off-target DNA breaks at loci that harbor highly active enhancers and display convergent transcription. The first active transcriptional profiles from acute lymphoblastic leukemia (ALL) patients acquired here reveal striking similarity at structural variation (SV) sites. Specific transcriptional features, namely convergent transcription and Pol2 stalling, were detected at breakpoints. The overlap was most prominent at SV with recognition motifs for the recombination activating genes (RAG). We present signal feature analysis to detect vulnerable regions and quantified from human cells how convergent transcription contributes to R-loop generation and RNA polymerase stalling. Wide stalling regions were characterized by high DNAse hypersensitivity and unusually broad H3K4me3 signal. Based on 1382 pre-B-ALL patients, the ETV6-RUNX1 fusion positive patients had over ten-fold elevation in RAG1 while high expression of AID marked pre-B-ALL lacking common cytogenetic changes. DOI: http://dx.doi.org/10.7554/eLife.13087.001 PMID:27431763

  16. Spatial and temporal variations in the age structure of Arctic sea ice

    USGS Publications Warehouse

    Belchansky, G.I.; Douglas, D.C.; Platonov, N.G.

    2005-01-01

    Spatial and temporal variations in the age structure of Arctic sea ice are investigated using a new reversechronology algorithm that tracks ice-covered pixels to their location and date of origin based on ice motion and concentration data. The Beaufort Gyre tends to harbor the oldest (>10 years old) sea ice in the western Arctic while direct ice advection pathways toward the Transpolar Drift Stream maintain relatively young (???5 years) ice in the eastern Arctic. Persistent net losses (-4.2% yr-1) in extent of ice >10 years old (10+ year age class) were observed during 1989-2003. Since the mid-1990s, losses to the 10+ year age class lacked compensation by recruitment due to a prior depletion of all mature (6-10 year) age classes. Survival of the 1994 and 1996-1998 sea ice generations reestablished most mature age classes, and thereby the potential to increase extent of the 10+ year age class during the mid-2000s. Copyright 2005 by the American Geophysical Union.

  17. Seasonal variation in the copepod community structure from a tropical Amazon estuary, Northern Brazil.

    PubMed

    Magalhães, André; Leite, Natália da R; Silva, João G S; Pereira, Luci C C; Costa, Rauquírio M da

    2009-06-01

    The main purpose of this study was to investigate the seasonal variation of copepod community structure during the months of July, September and November 2003 (dry season) and January, March and May 2004 (rainy season) in the Curuçá estuary, northern Brazil. Samples were collected during neap tides via gentle 200microm mesh net tows from a small powerboat. Measurements of surface water conductivity were accomplished in situ using an electronic conductivimeter and salinity was later obtained through the transformation of the conductivity values. Salinity varied seasonally from 7.2 +/- 0.1 to 39.2 +/- 1.8 (mean +/- standard deviation) and was influenced mainly by differences in the amount of rainfall between the studied sampling seasons. In total, 30 Copepoda taxa were identified and Acartia tonsa comprised the most representative species throughout the entire studied period followed by Acartia lilljeborgii, Subeucalanus pileatus and Paracalanus quasimodo. In the present study, the density values, ecological indexes and copepod species dominance presented a clear seasonal pattern, showing that the studied area may be considered seasonally heterogeneous in relation to the investigated parameters. PMID:19488623

  18. COSMOS: accurate detection of somatic structural variations through asymmetric comparison between tumor and normal samples.

    PubMed

    Yamagata, Koichi; Yamanishi, Ayako; Kokubu, Chikara; Takeda, Junji; Sese, Jun

    2016-05-01

    An important challenge in cancer genomics is precise detection of structural variations (SVs) by high-throughput short-read sequencing, which is hampered by the high false discovery rates of existing analysis tools. Here, we propose an accurate SV detection method named COSMOS, which compares the statistics of the mapped read pairs in tumor samples with isogenic normal control samples in a distinct asymmetric manner. COSMOS also prioritizes the candidate SVs using strand-specific read-depth information. Performance tests on modeled tumor genomes revealed that COSMOS outperformed existing methods in terms of F-measure. We also applied COSMOS to an experimental mouse cell-based model, in which SVs were induced by genome engineering and gamma-ray irradiation, followed by polymerase chain reaction-based confirmation. The precision of COSMOS was 84.5%, while the next best existing method was 70.4%. Moreover, the sensitivity of COSMOS was the highest, indicating that COSMOS has great potential for cancer genome analysis. PMID:26833260

  19. The average solar wind in the inner heliosphere: Structures and slow variations

    NASA Technical Reports Server (NTRS)

    Schwenn, R.

    1983-01-01

    Measurements from the HELIOS solar probes indicated that apart from solar activity related disturbances there exist two states of the solar wind which might result from basic differences in the acceleration process: the fast solar wind (v 600 kms(-)1) emanating from magnetically open regions in the solar corona and the "slow" solar wind (v 400 kms(-)1) correlated with the more active regions and its mainly closed magnetic structures. In a comprehensive study using all HELIOS data taken between 1974 and 1982 the average behavior of the basic plasma parameters were analyzed as functions of the solar wind speed. The long term variations of the solar wind parameters along the solar cycle were also determined and numerical estimates given. These modulations appear to be distinct though only minor. In agreement with earlier studies it was concluded that the major modulations are in the number and size of high speed streams and in the number of interplanetary shock waves caused by coronal transients. The latter ones usually cause huge deviations from the averages of all parameters.

  20. Population structure and cryptic genetic variation in the mango fruit fly, Ceratitis cosyra (Diptera, Tephritidae)

    PubMed Central

    Virgilio, Massimiliano; Delatte, Hélène; Nzogela, Yasinta Beda; Simiand, Christophe; Quilici, Serge; De Meyer, Marc; Mwatawala, Maulid

    2015-01-01

    Abstract The fruit fly Ceratitis cosyra is an important agricultural pest negatively affecting the mango crop production throughout Africa and also feeding on a variety of other wild and cultivated hosts. The occurrence of deeply divergent haplotypes, as well as extensive morphological variability, previously suggested possible cryptic speciation within Ceratitis cosyra. Here we provide the first large-scale characterisation of the population structure of Ceratitis cosyra with the main objective of verifying cryptic genetic variation. A total of 348 specimens from 13 populations were genotyped at 16 polymorphic microsatellite loci. Hardy-Weinberg equilibrium (HWE) deviations were observed in 40.4% of locus-population combinations and suggested the occurrence of genetic substructuring within populations. Discriminant Analysis of Principal Components (DAPC) showed genetic divergence between the vast majority of vouchers from Burundi and Tanzania (plus a few outliers from other African countries) and all other specimens sampled. Individual Bayesian assignments confirmed the existence of two main genotypic groups also occurring in sympatry. These data provided further support to the hypothesis that Ceratitis cosyra might include cryptic species. However, additional integrative taxonomy, possibly combining morphological, ecological and physiological approaches, is required to provide the necessary experimental support to this model. PMID:26798276

  1. Pentopyranosyl Oligonucleotide Systems. Part 11: Systems with Shortened Backbones: D)-beta-Ribopyranosyl-(4 yields 3 )- and (L)-alpha - Lyxopyranosyl-(4 yields 3 )-oligonucleotides

    NASA Technical Reports Server (NTRS)

    Wippo, Harald; Reck, Folkert; Kudick, Rene; Ramaseshan, Mahesh; Ceulemans, Griet; Bolli, Martin; Krishnamurthy, Ramanarayanan; Eschenmoser, Albert

    2001-01-01

    The (L)-a-lyxopyranosyl-(4'yields 3')-oligonucleotide system-a member of a pentopyranosyl oligonucleotide family containing a shortened backbone-is capable of cooperative base-pairing and of cross-pairing with DNA and RNA. In contrast, corresponding (D)-beta-ribopyransoyl-(4' yields 3')-oligonucleotides do not show base-pairing under similar conditions. We conclude that oligonucleotide systems can violate the six-bonds-per-backbone-unit rule by having five bonds instead, if their vicinally bound phosphodiester bridges can assume an antiperiplanar conformation. An additional structural feature that seems relevant to the cross-pairing capability of the (L)-a-lyxopyranosyl-(4' yields 3')-oligonucleotide system is its (small) backbone/basepair axes inclination. An inclination which is similar to that in B-DNA seems to be a prerequisite for an oligonucleotide system s capability to cross-pair with DNA.

  2. Sequential backbone resonance assignments of the E. coli dihydrofolate reductase Gly67Val mutant: folate complex.

    PubMed

    Puthenpurackal Narayanan, Sunilkumar; Maeno, Akihiro; Wada, Yuji; Tate, Shin-Ichi; Akasaka, Kazuyuki

    2016-04-01

    Occasionally, a mutation in an exposed loop region causes a significant change in protein function and/or stability. A single mutation Gly67Val of E. coli dihydrofolate reductase (DHFR) in the exposed CD loop is such an example. We have carried out the chemical shift assignments for H(N), N(H), C(α) and C(β) atoms of the Gly67Val mutant of E. coli DHFR complexed with folate at pH 7.0, 35 °C, and then evaluated the H(N), N(H), C(α) and C(β) chemical shift changes caused by the mutation. The result indicates that, while the overall secondary structure remains the same, the single mutation Gly67Val causes site-specific conformational changes of the polypeptide backbone restricted around the adenosine-binding subdomain (residues 38-88) and not in the distant catalytic domain. PMID:26482924

  3. Assignment of protein backbone resonances using connectivity, torsion angles and 13Calpha chemical shifts.

    PubMed

    Morris, Laura C; Valafar, Homayoun; Prestegard, James H

    2004-05-01

    A program is presented which will return the most probable sequence location for a short connected set of residues in a protein given just (13)C(alpha) chemical shifts (delta((13)C(alpha))) and data restricting the phi and psi backbone angles. Data taken from both the BioMagResBank and the Protein Data Bank were used to create a probability density function (PDF) using a multivariate normal distribution in delta((13)C(alpha)), phi, and psi space for each amino acid residue. Extracting and combining probabilities for particular amino acid residues in a short proposed sequence yields a score indicative of the correctness of the proposed assignment. The program is illustrated using several proteins for which structure and (13)C(alpha) chemical shift data are available. PMID:15017135

  4. Novel Natural Oximes and Oxime Esters with a Vibralactone Backbone from the Basidiomycete Boreostereum vibrans

    PubMed Central

    Chen, He‐Ping; Zhao, Zhen‐Zhu; Li, Zheng‐Hui; Dong, Ze‐Jun; Wei, Kun; Bai, Xue; Zhang, Ling; Wen, Chun‐Nan

    2016-01-01

    Abstract A variety of novel natural products with significant bioactivities are produced by the basidiomycete Boreostereum vibrans. In the present study, we describe 16 novel natural oximes and oxime esters with a vibralactone backbone, vibralactoximes, which were isolated from the scale‐up fermentation broth of B. vibrans. Their structures were determined through extensive spectroscopic analyses. These compounds represent the first oxime esters from nature. The hypothetical biosynthetic pathway of these compounds was also proposed. Seven compounds exhibited significant pancreatic lipase inhibitory activity, while ten compounds exhibited cytotoxicities against five human cancer cell lines (HL‐60, SMMC‐7721, A‐549, MCF‐7, and SW480), with IC50 values comparable with those of cisplatin. PMID:27308232

  5. Side chain and backbone contributions of Phe508 to CFTR folding

    SciTech Connect

    Thibodeau, Patrick H.; Brautigam, Chad A.; Machius, Mischa; Thomas, Philip J.

    2010-12-07

    Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an integral membrane protein, cause cystic fibrosis (CF). The most common CF-causing mutant, deletion of Phe508, fails to properly fold. To elucidate the role Phe508 plays in the folding of CFTR, missense mutations at this position were generated. Only one missense mutation had a pronounced effect on the stability and folding of the isolated domain in vitro. In contrast, many substitutions, including those of charged and bulky residues, disrupted folding of full-length CFTR in cells. Structures of two mutant nucleotide-binding domains (NBDs) reveal only local alterations of the surface near position 508. These results suggest that the peptide backbone plays a role in the proper folding of the domain, whereas the side chain plays a role in defining a surface of NBD1 that potentially interacts with other domains during the maturation of intact CFTR.

  6. Backbone dynamics of the oligomerization domain of p53 determined from 15N NMR relaxation measurements.

    PubMed

    Clubb, R T; Omichinski, J G; Sakaguchi, K; Appella, E; Gronenborn, A M; Clore, G M

    1995-05-01

    The backbone dynamics of the tetrameric p53 oligomerization domain (residues 319-360) have been investigated by two-dimensional inverse detected heteronuclear 1H-15N NMR spectroscopy at 500 and 600 MHz. 15N T1, T2, and heteronuclear NOEs were measured for 39 of 40 non-proline backbone NH vectors at both field strengths. The overall correlation time for the tetramer, calculated from the T1/T2 ratios, was found to be 14.8 ns at 35 degrees C. The correlation times and amplitudes of the internal motions were extracted from the relaxation data using the model-free formalism (Lipari G, Szabo A, 1982, J Am Chem Soc 104:4546-4559). The internal dynamics of the structural core of the p53 oligomerization domain are uniform and fairly rigid, with residues 327-354 exhibiting an average generalized order parameter (S2) of 0.88 +/- 0.08. The N- and C-termini exhibit substantial mobility and are unstructured in the solution structure of p53. Residues located at the N- and C-termini, in the beta-sheet, in the turn between the alpha-helix and beta-sheet, and at the C-terminal end of the alpha-helix display two distinct internal motions that are faster than the overall correlation time. Fast internal motions (< or = 20 ps) are within the extreme narrowing limit and are of uniform amplitude. The slower motions (0.6-2.2 ns) are outside the extreme narrowing limit and vary in amplitude.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7663341

  7. Variations in Crustal Structure, Lithospheric Flexural Strength, and Isostatic Compensation Mechanisms of Mars

    NASA Astrophysics Data System (ADS)

    Ding, M.; Lin, J.; Zuber, M. T.

    2014-12-01

    We analyze gravity and topography of Mars to investigate the spatial variations in crustal thickness, lithospheric strength, and mechanisms of support of prominent topographic features on Mars. The latest gravity model JGMRO110c (released in 2012) from the Mars Reconnaissance Orbiter mission has a spatial block size resolution of ~97 km (corresponding to degree-110), enabling us to resolve crustal structures at higher spatial resolution than those determined from previous degree-80 and 85 gravity models [Zuber et al., 2000; McGovern et al., 2002, 2004; Neumann et al., 2004; Belleguic et al., 2005]. Using the latest gravity data, we first inverted for a new version of crustal thickness model of Mars assuming homogeneous crust and mantle densities of 2.9 and 3.5 g/cm3. We calculated "isostatic" topography for the Airy local isostatic compensation mechanism, and "non-isostatic" topography after removing the isostatic part. We find that about 92% of the Martian surface is in relatively isostatic state, indicating either relatively small lithospheric strength and/or small vertical loading. Relatively isostatic regions include the hemispheric dichotomy, Hellas and Argyre Planitia, Noachis and Arabia Terra, and Terra Cimmeria. In contrast, regions with significant amount of non-isostatic topography include the Olympus, Ascraeus, Arsia, Pavonis, Alba, and Elysium Mons, Isidis Planitia and Valles Marineris. Their relatively large "non-isostatc topography" implies relatively strong lithospheric strength and large vertical loading. Spectral analysis of the admittance and correlation relationship between gravity and topography were conducted for the non-isostatic regions using the localized spectra method [Wieczorek and Simons, 2005, 2007] and thin-shell lithospheric flexural approximation [Forsyth, 1985; McGovern et al., 2002, 2004]. The best-fitting models reveal significant variations in the effective lithospheric thickness with the greatest values for the Olympus Mon

  8. Population structure of nuclear and mitochondrial DNA variation among humpback whales in the North Pacific.

    PubMed

    Baker, C S; Medrano-Gonzalez, L; Calambokidis, J; Perry, A; Pichler, F; Rosenbaum, H; Straley, J M; Urban-Ramirez, J; Yamaguchi, M; von Ziegesar, O

    1998-06-01

    The population structure of variation in a nuclear actin intron and the control region of mitochondrial DNA is described for humpback whales from eight regions in the North Pacific Ocean: central California, Baja Peninsula, nearshore Mexico (Bahia Banderas), offshore Mexico (Socorro Island), southeastern Alaska, central Alaska (Prince Williams Sound), Hawaii and Japan (Ogasawara Islands). Primary mtDNA haplotypes and intron alleles were identified using selected restriction fragment length polymorphisms of target sequences amplified by the polymerase chain reaction (PCR-RFLP). There was little evidence of heterogeneity in the frequencies of mtDNA haplotypes or actin intron alleles due to the year or sex composition of the sample. However, frequencies of four mtDNA haplotypes showed marked regional differences in their distributions (phi ST = 0.277; P < 0.001; n = 205 individuals) while the two alleles showed significant, but less marked, regional differences (phi ST = 0.033; P < 0.013; n = 400 chromosomes). An hierarchical analysis of variance in frequencies of haplotypes and alleles supported the grouping of six regions into a central and eastern stock with further partitioning of variance among regions within stocks for haplotypes but not for alleles. Based on available genetic and demographic evidence, the southeastern Alaska and central California feeding grounds were selected for additional analyses of nuclear differentiation using allelic variation at four microsatellite loci. All four loci showed significant differences in allele frequencies (overall FST = 0.043; P < 0.001; average n = 139 chromosomes per locus), indicating at least partial reproductive isolation between the two regions as well as the segregation of mtDNA lineages. Although the two feeding grounds were not panmictic for nuclear or mitochondrial loci, estimates of long-term migration rates suggested that male-mediated gene flow was several-fold greater than female gene flow. These results

  9. A model of orientational ordering in phosphatidylcholine bilayers based on conformational analysis of the glycerol backbone region.

    PubMed Central

    Strenk, L M; Westerman, P W; Doane, J W

    1985-01-01

    Molecular and conformational ordering in aqueous multilamellar suspensions of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) have been examined by deuterium nuclear magnetic resonance (2H NMR) in the liquid crystalline (L alpha) phase. Motionally averaged quadrupolar splittings vQ from six sites in the vicinity of the glycerol backbone have been analyzed by a molecular frame and order matrix approach in which the usual assumption of a freely-rotating molecule is not invoked. By assuming a relatively rigid glycerol backbone region, the six vQ values are found to be consistent with a conformation of the glycerol backbone that is almost identical to that of one of the two structures in crystalline DMPC dihydrate (Pearson, R. H., and I. Pascher, 1979, Nature (Lond.) 281: 499-501). The orientation of the most-ordered axis of the DMPC molecule is found to be tilted at an angle of 27 +/- 2 degrees with respect to the long axis of the sn-1 chain in its extended all trans conformation. The ordering of the most ordered molecular axis with respect to the bilayer normal is expressed by an order parameter of Szz approximately equal to 0.6 +/- 0.1, consistent with values in analogous thermotropic liquid crystals. PMID:4074836

  10. Structure of a Northwest Atlantic Shelf Macofaurnal Assemblage with Respect to Seasonal Variation in Sediment Nutritional Quality

    EPA Science Inventory

    We examined temporal variation in the relationship between benthic macrofaunal assemblage structure and sediment nutritional quality, using core samples taken seasonally from a 232 m deep site in Wilkinson Basin, Gulf of Maine from October 2003 through August 2004. The benthic as...

  11. A comparison of lyman alpha and He lambda 10830 line structures and variations in early-type star atmospheres

    NASA Technical Reports Server (NTRS)

    Meisel, D. D.

    1974-01-01

    Line profiles were first obtained at maximum velocity separation of the spectroscopic binary Spica (alpha Vir), and then high resolution spectrophotometric images of selected features in the 1.1 micron spectrum of Comet Kohoutek were obtained in order to gain insight into the structures and variations in early-type star atmospheres.

  12. Structural and functional impacts of copy number variations on the cattle genome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although there have been significant advances in resolving the pattern and nature of single nucleotide polymorphisms (SNPs), similar realizations for larger, more complex forms of genetic variation have just emerged. Several recent publications reveal that copy number variations (CNVs) are common an...

  13. Regional variations in human patellar trabecular architecture and the structure of the proximal patellar tendon enthesis

    PubMed Central

    Toumi, H; Higashiyama, I; Suzuki, D; Kumai, T; Bydder, G; McGonagle, D; Emery, P; Fairclough, J; Benjamin, M

    2006-01-01

    Proximal patellar tendinopathy occurs as an overuse injury in sport and is also characteristic of ankylosing spondylitis patients. It particularly affects the posteromedial part of the patellar tendon enthesis, although the reason for this is unclear. We investigated whether there are regional differences in the trabecular architecture of the patella or in the histology of the patellar tendon enthesis that could suggest unequal force transmission from bone to tendon. Trabecular architecture was analysed from X-rays taken with a Faxitron radiography system of the patellae of dissecting room cadavers and in magnetic resonance images of the knees of living volunteers. Structural and fractal analyses were performed on the Faxitron digital images using MatLab software. Regional differences at the enthesis in the thickness of the uncalcified fibrocartilage and the subchondral plate were evaluated histologically in cadaveric material. The radiological studies showed that the quantity of bone and the apparent trabecular thickness in the patella were greatest medially, and that in the lateral part of the patella there were fewer trabeculae which were orientated either antero-posteriorly or superiorly inferiorly. The histological study showed that the uncalcified fibrocartilage was most prominent medially and that the subchondral plate was thinner laterally. Overall, the results indicate that mechanical stress at the proximal patellar tendon enthesis is asymmetrically distributed and greater on the medial than on the lateral side. Thus, we suggest that the functional anatomy of the knee is closely related to regional variations in force transmission, which in turn relates to the posteromedial site of pathology in proximal patellar tendinopathy. PMID:16420378

  14. Climate structures genetic variation across a species' elevation range: a test of range limits hypotheses.

    PubMed

    Sexton, Jason P; Hufford, Matthew B; Bateman, Ashley C; Lowry, David B; Meimberg, Harald; Strauss, Sharon Y; Rice, Kevin J

    2016-02-01

    Gene flow may influence the formation of species range limits, and yet little is known about the patterns of gene flow with respect to environmental gradients or proximity to range limits. With rapid environmental change, it is especially important to understand patterns of gene flow to inform conservation efforts. Here we investigate the species range of the selfing, annual plant, Mimulus laciniatus, in the California Sierra Nevada. We assessed genetic variation, gene flow, and population abundance across the entire elevation-based climate range. Contrary to expectations, within-population plant density increased towards both climate limits. Mean genetic diversity of edge populations was equivalent to central populations; however, all edge populations exhibited less genetic diversity than neighbouring interior populations. Genetic differentiation was fairly consistent and moderate among all populations, and no directional signals of contemporary gene flow were detected between central and peripheral elevations. Elevation-driven gene flow (isolation by environment), but not isolation by distance, was found across the species range. These findings were the same towards high- and low-elevation range limits and were inconsistent with two common centre-edge hypotheses invoked for the formation of species range limits: (i) decreasing habitat quality and population size; (ii) swamping gene flow from large, central populations. This pattern demonstrates that climate, but not centre-edge dynamics, is an important range-wide factor structuring M. laciniatus populations. To our knowledge, this is the first empirical study to relate environmental patterns of gene flow to range limits hypotheses. Similar investigations across a wide variety of taxa and life histories are needed. PMID:26756973

  15. A structure-activity analysis of the variation in oxime efficacy against nerve agents.

    PubMed

    Maxwell, Donald M; Koplovitz, Irwin; Worek, Franz; Sweeney, Richard E

    2008-09-01

    A structure-activity analysis was used to evaluate the variation in oxime efficacy of 2-PAM, obidoxime, HI-6 and ICD585 against nerve agents. In vivo oxime protection and in vitro oxime reactivation were used as indicators of oxime efficacy against VX, sarin, VR and cyclosarin. Analysis of in vivo oxime protection was conducted with oxime protective ratios (PR) from guinea pigs receiving oxime and atropine therapy after sc administration of nerve agent. Analysis of in vitro reactivation was conducted with second-order rate contants (k(r2)) for oxime reactivation of agent-inhibited acetylcholinesterase (AChE) from guinea pig erythrocytes. In vivo oxime PR and in vitro k(r2) decreased as the volume of the alkylmethylphosphonate moiety of nerve agents increased from VX to cyclosarin. This effect was greater with 2-PAM and obidoxime (>14-fold decrease in PR) than with HI-6 and ICD585 (<3.7-fold decrease in PR). The decrease in oxime PR and k(r2) as the volume of the agent moiety conjugated to AChE increased was consistent with a steric hindrance mechanism. Linear regression of log (PR-1) against log (k(r2)[oxime dose]) produced two offset parallel regression lines that delineated a significant difference between the coupling of oxime reactivation and oxime protection for HI-6 and ICD585 compared to 2-PAM and obidoxime. HI-6 and ICD585 appeared to be 6.8-fold more effective than 2-PAM and obidoxime at coupling oxime reactivation to oxime protection, which suggested that the isonicotinamide group that is common to both of these oximes, but absent from 2-PAM and obidoxime, is important for oxime efficacy. PMID:18508103

  16. Perturbing the Copper(III)-Hydroxide Unit through Ligand Structural Variation.

    PubMed

    Dhar, Debanjan; Yee, Gereon M; Spaeth, Andrew D; Boyce, David W; Zhang, Hongtu; Dereli, Büsra; Cramer, Christopher J; Tolman, William B

    2016-01-13

    Two new ligand sets, (pipMe)LH2 and (NO2)LH2 ((pipMe)L = N,N'-bis(2,6-diisopropylphenyl)-1-methylpiperidine-2,6-dicarboxamide, (NO2)L = N,N'-bis(2,6-diisopropyl-4-nitrophenyl)pyridine-2,6-dicarboxamide), are reported which are designed to perturb the overall electronics of the copper(III)-hydroxide core and the resulting effects on the thermodynamics and kinetics of its hydrogen-atom abstraction (HAT) reactions. Bond dissociation energies (BDEs) for the O-H bonds of the corresponding Cu(II)-OH2 complexes were measured that reveal that changes in the redox potential for the Cu(III)/Cu(II) couple are only partially offset by opposite changes in the pKa, leading to modest differences in BDE among the three compounds. The effects of these changes were further probed by evaluating the rates of HAT by the corresponding Cu(III)-hydroxide complexes from substrates with C-H bonds of variable strength. These studies revealed an overarching linear trend in the relationship between the log k (where k is the second-order rate constant) and the ΔH of reaction. Additional subtleties in measured rates arise, however, that are associated with variations in hydrogen-atom abstraction barrier heights and tunneling efficiencies over the temperature range from -80 to -20 °C, as inferred from measured kinetic isotope effects and corresponding electronic-structure-based transition-state theory calculations. PMID:26693733

  17. Structural variation detection using next-generation sequencing data: A comparative technical review.

    PubMed

    Guan, Peiyong; Sung, Wing-Kin

    2016-06-01

    Structural variations (SVs) are mutations in the genome of size at least fifty nucleotides. They contribute to the phenotypic differences among healthy individuals, cause severe diseases and even cancers by breaking or linking genes. Thus, it is crucial to systematically profile SVs in the genome. In the past decade, many next-generation sequencing (NGS)-based SV detection methods have been proposed due to the significant cost reduction of NGS experiments and their ability to unbiasedly detect SVs to the base-pair resolution. These SV detection methods vary in both sensitivity and specificity, since they use different SV-property-dependent and library-property-dependent features. As a result, predictions from different SV callers are often inconsistent. Besides, the noises in the data (both platform-specific sequencing error and artificial chimeric reads) impede the specificity of SV detection. Poorly characterized regions in the human genome (e.g., repeat regions) greatly impact the reads mapping and in turn affect the SV calling accuracy. Calling of complex SVs requires specialized SV callers. Apart from accuracy, processing speed of SV caller is another factor deciding its usability. Knowing the pros and cons of different SV calling techniques and the objectives of the biological study are essential for biologists and bioinformaticians to make informed decisions. This paper describes different components in the SV calling pipeline and reviews the techniques used by existing SV callers. Through simulation study, we also demonstrate that library properties, especially insert size, greatly impact the sensitivity of different SV callers. We hope the community can benefit from this work both in designing new SV calling methods and in selecting the appropriate SV caller for specific biological studies. PMID:26845461

  18. Changes in the shape of cloud ice water content vertical structure due to aerosol variations

    NASA Astrophysics Data System (ADS)

    Massie, Steven T.; Delanoë, Julien; Bardeen, Charles G.; Jiang, Jonathan H.; Huang, Lei

    2016-05-01

    Changes in the shape of cloud ice water content (IWC) vertical structure due to variations in Moderate Resolution Imaging Spectroradiometer (MODIS) aerosol optical depths (AODs), Ozone Monitoring Instrument (OMI) absorptive aerosol optical depths (AAODs), and Microwave Limb Sounder (MLS) CO (an absorptive aerosol proxy) at 215 hPa are calculated in the Tropics during 2007-2010 based upon an analysis of DARDAR IWC profiles for deep convective clouds. DARDAR profiles are a joint retrieval of CloudSat-CALIPSO data. Analysis is performed for 12 separate regions over land and ocean, and carried out applying MODIS AOD fields that attempt to correct for 3-D cloud adjacency effects. The 3-D cloud adjacency effects have a small impact upon our particular calculations of aerosol-cloud indirect effects. IWC profiles are averaged for three AOD bins individually for the 12 regions. The IWC average profiles are also normalized to unity at 5 km altitude in order to study changes in the shape of the average IWC profiles as AOD increases. Derivatives of the IWC average profiles, and derivatives of the IWC shape profiles, in percent change per 0.1 change in MODIS AOD units, are calculated separately for each region. Means of altitude-specific probability distribution functions, which include both ocean and land IWC shape regional derivatives, are modest, near 5 %, and positive to the 2σ level between 11 and 15 km altitude. Similar analyses are carried out for three AAOD and three CO bins. On average, the vertical profiles of the means of the derivatives based upon the profile shapes over land and ocean are smaller for the profiles binned according to AAOD and CO values, than for the MODIS AODs, which include both scattering and absorptive aerosol. This difference in character supports the assertion that absorptive aerosol can inhibit cloud development.

  19. WIND STRUCTURE AND LUMINOSITY VARIATIONS IN THE WOLF-RAYET/LUMINOUS BLUE VARIABLE HD 5980

    SciTech Connect

    Georgiev, Leonid; Koenigsberger, Gloria; Hillier, D. John; Morrell, Nidia; Gamen, Roberto E-mail: gloria@astro.unam.mx

    2011-12-15

    Over the past 40 years, the massive luminous blue variable/Wolf-Rayet system HD 5980 in the Small Magellanic Cloud (SMC) has undergone a long-term S Doradus-type variability cycle and two brief and violent eruptions in 1993 and 1994. In this paper we analyze a collection of UV and optical spectra obtained between 1979 and 2009 and perform CMFGEN model fits to spectra of 1994, 2000, 2002, and 2009. The results are as follows: (1) the long-term S Dor-type variability is associated with changes of the hydrostatic radius; (2) the 1994 eruption involved changes in its bolometric luminosity and wind structure; (3) the emission-line strength, the wind velocity, and the continuum luminosity underwent correlated variations in the sense that a decreasing V{sub {infinity}} is associated with increasing emission line and continuum levels; and (4) the spectrum of the third star in the system (Star C) is well fit by a T{sub eff} = 32 K model atmosphere with SMC chemical abundances. For all epochs, the wind of the erupting star is optically thick at the sonic point and is thus driven mainly by the continuum opacity. We speculate that the wind switches between two stable regimes driven by the 'hot' (during the eruption) and the 'cool' (post-eruption) iron opacity bumps as defined by Lamers and Nugis and Graefener and Hamann, and thus the wind may undergo a bi-stability jump of a different nature from that which occurs in OB stars.

  20. Whole-Genome Sequencing Reveals Diverse Models of Structural Variations in Esophageal Squamous Cell Carcinoma.

    PubMed

    Cheng, Caixia; Zhou, Yong; Li, Hongyi; Xiong, Teng; Li, Shuaicheng; Bi, Yanghui; Kong, Pengzhou; Wang, Fang; Cui, Heyang; Li, Yaoping; Fang, Xiaodong; Yan, Ting; Li, Yike; Wang, Juan; Yang, Bin; Zhang, Ling; Jia, Zhiwu; Song, Bin; Hu, Xiaoling; Yang, Jie; Qiu, Haile; Zhang, Gehong; Liu, Jing; Xu, Enwei; Shi, Ruyi; Zhang, Yanyan; Liu, Haiyan; He, Chanting; Zhao, Zhenxiang; Qian, Yu; Rong, Ruizhou; Han, Zhiwei; Zhang, Yanlin; Luo, Wen; Wang, Jiaqian; Peng, Shaoliang; Yang, Xukui; Li, Xiangchun; Li, Lin; Fang, Hu; Liu, Xingmin; Ma, Li; Chen, Yunqing; Guo, Shiping; Chen, Xing; Xi, Yanfeng; Li, Guodong; Liang, Jianfang; Yang, Xiaofeng; Guo, Jiansheng; Jia, JunMei; Li, Qingshan; Cheng, Xiaolong; Zhan, Qimin; Cui, Yongping

    2016-02-01

    Comprehensive identification of somatic structural variations (SVs) and understanding their mutational mechanisms in cancer might contribute to understanding biological differences and help to identify new therapeutic targets. Unfortunately, characterization of complex SVs across the whole genome and the mutational mechanisms underlying esophageal squamous cell carcinoma (ESCC) is largely unclear. To define a comprehensive catalog of somatic SVs, affected target genes, and their underlying mechanisms in ESCC, we re-analyzed whole-genome sequencing (WGS) data from 31 ESCCs using Meerkat algorithm to predict somatic SVs and Patchwork to determine copy-number changes. We found deletions and translocations with NHEJ and alt-EJ signature as the dominant SV types, and 16% of deletions were complex deletions. SVs frequently led to disruption of cancer-associated genes (e.g., CDKN2A and NOTCH1) with different mutational mechanisms. Moreover, chromothripsis, kataegis, and breakage-fusion-bridge (BFB) were identified as contributing to locally mis-arranged chromosomes that occurred in 55% of ESCCs. These genomic catastrophes led to amplification of oncogene through chromothripsis-derived double-minute chromosome formation (e.g., FGFR1 and LETM2) or BFB-affected chromosomes (e.g., CCND1, EGFR, ERBB2, MMPs, and MYC), with approximately 30% of ESCCs harboring BFB-derived CCND1 amplification. Furthermore, analyses of copy-number alterations reveal high frequency of whole-genome duplication (WGD) and recurrent focal amplification of CDCA7 that might act as a potential oncogene in ESCC. Our findings reveal molecular defects such as chromothripsis and BFB in malignant transformation of ESCCs and demonstrate diverse models of SVs-derived target genes in ESCCs. These genome-wide SV profiles and their underlying mechanisms provide preventive, diagnostic, and therapeutic implications for ESCCs. PMID:26833333

  1. Whole-Genome Sequencing Reveals Diverse Models of Structural Variations in Esophageal Squamous Cell Carcinoma

    PubMed Central

    Cheng, Caixia; Zhou, Yong; Li, Hongyi; Xiong, Teng; Li, Shuaicheng; Bi, Yanghui; Kong, Pengzhou; Wang, Fang; Cui, Heyang; Li, Yaoping; Fang, Xiaodong; Yan, Ting; Li, Yike; Wang, Juan; Yang, Bin; Zhang, Ling; Jia, Zhiwu; Song, Bin; Hu, Xiaoling; Yang, Jie; Qiu, Haile; Zhang, Gehong; Liu, Jing; Xu, Enwei; Shi, Ruyi; Zhang, Yanyan; Liu, Haiyan; He, Chanting; Zhao, Zhenxiang; Qian, Yu; Rong, Ruizhou; Han, Zhiwei; Zhang, Yanlin; Luo, Wen; Wang, Jiaqian; Peng, Shaoliang; Yang, Xukui; Li, Xiangchun; Li, Lin; Fang, Hu; Liu, Xingmin; Ma, Li; Chen, Yunqing; Guo, Shiping; Chen, Xing; Xi, Yanfeng; Li, Guodong; Liang, Jianfang; Yang, Xiaofeng; Guo, Jiansheng; Jia, JunMei; Li, Qingshan; Cheng, Xiaolong; Zhan, Qimin; Cui, Yongping

    2016-01-01

    Comprehensive identification of somatic structural variations (SVs) and understanding their mutational mechanisms in cancer might contribute to understanding biological differences and help to identify new therapeutic targets. Unfortunately, characterization of complex SVs across the whole genome and the mutational mechanisms underlying esophageal squamous cell carcinoma (ESCC) is largely unclear. To define a comprehensive catalog of somatic SVs, affected target genes, and their underlying mechanisms in ESCC, we re-analyzed whole-genome sequencing (WGS) data from 31 ESCCs using Meerkat algorithm to predict somatic SVs and Patchwork to determine copy-number changes. We found deletions and translocations with NHEJ and alt-EJ signature as the dominant SV types, and 16% of deletions were complex deletions. SVs frequently led to disruption of cancer-associated genes (e.g., CDKN2A and NOTCH1) with different mutational mechanisms. Moreover, chromothripsis, kataegis, and breakage-fusion-bridge (BFB) were identified as contributing to locally mis-arranged chromosomes that occurred in 55% of ESCCs. These genomic catastrophes led to amplification of oncogene through chromothripsis-derived double-minute chromosome formation (e.g., FGFR1 and LETM2) or BFB-affected chromosomes (e.g., CCND1, EGFR, ERBB2, MMPs, and MYC), with approximately 30% of ESCCs harboring BFB-derived CCND1 amplification. Furthermore, analyses of copy-number alterations reveal high frequency of whole-genome duplication (WGD) and recurrent focal amplification of CDCA7 that might act as a potential oncogene in ESCC. Our findings reveal molecular defects such as chromothripsis and BFB in malignant transformation of ESCCs and demonstrate diverse models of SVs-derived target genes in ESCCs. These genome-wide SV profiles and their underlying mechanisms provide preventive, diagnostic, and therapeutic implications for ESCCs. PMID:26833333

  2. Variation in xylem structure from tropics to tundra: Evidence from vestured pits

    PubMed Central

    Jansen, Steven; Baas, Pieter; Gasson, Peter; Lens, Frederic; Smets, Erik

    2004-01-01

    Bordered pits play an important role in permitting water flow among adjacent tracheary elements in flowering plants. Variation in the bordered pit structure is suggested to be adaptive in optimally balancing the conflict between hydraulic efficiency (conductivity) and safety from air entry at the pit membrane (air seeding). The possible function of vestured pits, which are bordered pits with protuberances from the secondary cell wall of the pit chamber, could be increased hydraulic resistance or minimized vulnerability to air seeding. These functional hypotheses have to be harmonized with the notion that the vestured or nonvestured nature of pits contains strong phylogenetic signals (i.e., often characterize large species-rich clades with broad ecological ranges). A literature survey of 11,843 species covering 6,428 genera from diverse climates indicates that the incidence of vestured pits considerably decreases from tropics to tundra. The highest frequencies of vestured pits occur in deserts and tropical seasonal woodlands. Moreover, a distinctly developed network of branched vestures is mainly restricted to warm habitats in both mesic and dry (sub)tropical lowlands, whereas vestures in woody plants from cold and boreal arctic environments are usually minute and simple. A similar survey of the frequency of exclusively scalariform perforation plates illustrates that the major ecological trend of this feature is opposite that of vestured pits. These findings provide previously undescribed insights suggesting that vessels with vestured pits and simple perforation plates function as an efficient hydraulic system in plants growing in warm environments with periodical or continuous drought stress. PMID:15163796

  3. A structure-activity analysis of the variation in oxime efficacy against nerve agents

    SciTech Connect

    Maxwell, Donald M. Koplovitz, Irwin; Worek, Franz; Sweeney, Richard E.

    2008-09-01

    A structure-activity analysis was used to evaluate the variation in oxime efficacy of 2-PAM, obidoxime, HI-6 and ICD585 against nerve agents. In vivo oxime protection and in vitro oxime reactivation were used as indicators of oxime efficacy against VX, sarin, VR and cyclosarin. Analysis of in vivo oxime protection was conducted with oxime protective ratios (PR) from guinea pigs receiving oxime and atropine therapy after sc administration of nerve agent. Analysis of in vitro reactivation was conducted with second-order rate contants (k{sub r2}) for oxime reactivation of agent-inhibited acetylcholinesterase (AChE) from guinea pig erythrocytes. In vivo oxime PR and in vitro k{sub r2} decreased as the volume of the alkylmethylphosphonate moiety of nerve agents increased from VX to cyclosarin. This effect was greater with 2-PAM and obidoxime (> 14-fold decrease in PR) than with HI-6 and ICD585 (< 3.7-fold decrease in PR). The decrease in oxime PR and k{sub r2} as the volume of the agent moiety conjugated to AChE increased was consistent with a steric hindrance mechanism. Linear regression of log (PR-1) against log (k{sub r2} {center_dot} [oxime dose]) produced two offset parallel regression lines that delineated a significant difference between the coupling of oxime reactivation and oxime protection for HI-6 and ICD585 compared to 2-PAM and obidoxime. HI-6 and ICD585 appeared to be 6.8-fold more effective than 2-PAM and obidoxime at coupling oxime reactivation to oxime protection, which suggested that the isonicotinamide group that is common to both of these oximes, but absent from 2-PAM and obidoxime, is important for oxime efficacy.

  4. Modeling deformation induced by seasonal variations of continental water in the Himalaya region: Sensitivity to Earth elastic structure

    NASA Astrophysics Data System (ADS)

    Chanard, K.; Avouac, J. P.; Ramillien, G.; Genrich, J.

    2014-06-01

    Strong seasonal variations of horizontal and vertical positions are observed on GPS time series from stations located in Nepal, India, and Tibet (China). We show that this geodetic deformation can be explained by seasonal variations of continental water storage driven by the monsoon. For this purpose, we use satellite data from the Gravity Recovery and Climate Experiment to determine the time evolution of surface loading. We compute the expected geodetic deformation assuming a perfectly elastic Earth model. We consider Green's functions, describing the surface deformation response to a point load, for an elastic homogeneous half-space model and for a layered nonrotating spherical Earth model based on the Preliminary Reference Earth Model and a local seismic velocity model. The amplitude and phase of the seasonal variation of the vertical and horizontal geodetic positions can be jointly adjusted only with the layered Earth model, while an elastic half-space model fails, emphasizing the importance of using a realistic Earth elastic structure to model surface displacements induced by surface loading. We demonstrate, based on a formal inversion, that the fit to the geodetic data can be improved by adjusting the layered Earth model. Therefore, the study also shows that the modeling of geodetic seasonal variations provides a way to probe the elastic structure of the Earth, even in the absence of direct measurements of surface load variations.

  5. The Relationship between Gene Network Structure and Expression Variation among Individuals and Species.

    PubMed

    Sears, Karen E; Maier, Jennifer A; Rivas-Astroza, Marcelo; Poe, Rachel; Zhong, Sheng; Kosog, Kari; Marcot, Jonathan D; Behringer, Richard R; Cretekos, Chris J; Rasweiler, John J; Rapti, Zoi

    2015-08-01

    Variation among individuals is a prerequisite of evolution by natural selection. As such, identifying the origins of variation is a fundamental goal of biology. We investigated the link between gene interactions and variation in gene expression among individuals and species using the mammalian limb as a model system. We first built interaction networks for key genes regulating early (outgrowth; E9.5-11) and late (expansion and elongation; E11-13) limb development in mouse. This resulted in an Early (ESN) and Late (LSN) Stage Network. Computational perturbations of these networks suggest that the ESN is more robust. We then quantified levels of the same key genes among mouse individuals and found that they vary less at earlier limb stages and that variation in gene expression is heritable. Finally, we quantified variation in gene expression levels among four mammals with divergent limbs (bat, opossum, mouse and pig) and found that levels vary less among species at earlier limb stages. We also found that variation in gene expression levels among individuals and species are correlated for earlier and later limb development. In conclusion, results are consistent with the robustness of the ESN buffering among-individual variation in gene expression levels early in mammalian limb development, and constraining the evolution of early limb development among mammalian species. PMID:26317994

  6. The Relationship between Gene Network Structure and Expression Variation among Individuals and Species

    PubMed Central

    Sears, Karen E.; Maier, Jennifer A.; Rivas-Astroza, Marcelo; Poe, Rachel; Zhong, Sheng; Kosog, Kari; Marcot, Jonathan D.; Behringer, Richard R.; Rasweiler, John J.; Rapti, Zoi

    2015-01-01

    Abstract Variation among individuals is a prerequisite of evolution by natural selection. As such, identifying the origins of variation is a fundamental goal of biology. We investigated the link between gene interactions and variation in gene expression among individuals and species using the mammalian limb as a model system. We first built interaction networks for key genes regulating early (outgrowth; E9.5–11) and late (expansion and elongation; E11-13) limb development in mouse. This resulted in an Early (ESN) and Late (LSN) Stage Network. Computational perturbations of these networks suggest that the ESN is more robust. We then quantified levels of the same key genes among mouse individuals and found that they vary less at earlier limb stages and that variation in gene expression is heritable. Finally, we quantified variation in gene expression levels among four mammals with divergent limbs (bat, opossum, mouse and pig) and found that levels vary less among species at earlier limb stages. We also found that variation in gene expression levels among individuals and species are correlated for earlier and later limb development. In conclusion, results are consistent with the robustness of the ESN buffering among-individual variation in gene expression levels early in mammalian limb development, and constraining the evolution of early limb development among mammalian species. PMID:26317994

  7. Pendant Dynamics of Ethylene-Oxide Containing Polymers with Diverse Backbones

    NASA Astrophysics Data System (ADS)

    Bartels, Joshua; Wang, Jing-Han Helen; Chen, Quan; Runt, James; Colby, Ralph

    In the last twenty years, a wide variety of ion conducting polymers have used ether oxygens to facilitate ion conduction, and it is therefore important to understand the dynamics of ether oxygens (EOs) when attached to different polymer backbones. Four different EO-containing polymer architectures are studied by dielectric spectroscopy to understand the backbone effect on the EO dipoles. Polysiloxanes, polyphosphazenes, polymethylmethacrylates, and a polyester ether are compared, with different EO pendant lengths for the siloxane and methylmethacrylate backbones. The flexible polysiloxanes and polyphosphazene backbones impart superior segmental mobility with a glass transition temperature 15 K lower than that of the organic backbone polymers. Short EO pendants are found to impart a lower static dielectric constant at comparable EO content as compared to longer EO pendants of either inorganic or organic backbones. The long-pendant polymethylmethacrylate polymers show two relaxations corresponding to fast EOs near the pendant tail end and slow EOs close to the slower backbone, whereas the long-pendant polysiloxane shows a single relaxation due to the siloxane backbone relaxing faster than the EO pendant. Supported by the NSF Division of Materials Research Polymers Program through Grants DMR-1404586 (RHC) and DMR-1505953 (JR).

  8. Live-attenuated influenza A virus vaccines using a B virus backbone

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The currently FDA-licensed live attenuated influenza virus vaccine contains a trivalent mixture of types A (H1N1 and H3N2) and B vaccine viruses. The two A virus vaccines have the backbone of a cold-adapted influenza A virus and the B virus vaccine has the six backbone segments derived from a cold-...

  9. Quantitative Analysis of PMLA Nanoconjugate Components after Backbone Cleavage

    PubMed Central

    Ding, Hui; Patil, Rameshwar; Portilla-Arias, Jose; Black, Keith L.; Ljubimova, Julia Y.; Holler, Eggehard

    2015-01-01

    Multifunctional polymer nanoconjugates containing multiple components show great promise in cancer therapy, but in most cases complete analysis of each component is difficult. Polymalic acid (PMLA) based nanoconjugates have demonstrated successful brain and breast cancer treatment. They consist of multiple components including targeting antibodies, Morpholino antisense oligonucleotides (AONs), and endosome escape moieties. The component analysis of PMLA nanoconjugates is extremely difficult using conventional spectrometry and HPLC method. Taking advantage of the nature of polyester of PMLA, which can be cleaved by ammonium hydroxide, we describe a method to analyze the content of antibody and AON within nanoconjugates simultaneously using SEC-HPLC by selectively cleaving the PMLA backbone. The selected cleavage conditions only degrade PMLA without affecting the integrity and biological activity of the antibody. Although the amount of antibody could also be determined using the bicinchoninic acid (BCA) method, our selective cleavage method gives more reliable results and is more powerful. Our approach provides a new direction for the component analysis of polymer nanoconjugates and nanoparticles. PMID:25894227

  10. Backbones of evolutionary history test biodiversity theory for microbes

    PubMed Central

    O’Dwyer, James P.; Kembel, Steven W.; Sharpton, Thomas J.

    2015-01-01

    Identifying the ecological and evolutionary mechanisms that determine biological diversity is a central question in ecology. In microbial ecology, phylogenetic diversity is an increasingly common and relevant means of quantifying community diversity, particularly given the challenges in defining unambiguous species units from environmental sequence data. We explore patterns of phylogenetic diversity across multiple bacterial communities drawn from different habitats and compare these data to evolutionary trees generated using theoretical models of biodiversity. We have two central findings. First, although on finer scales the empirical trees are highly idiosyncratic, on coarse scales the backbone of these trees is simple and robust, consistent across habitats, and displays bursts of diversification dotted throughout. Second, we find that these data demonstrate a clear departure from the predictions of standard neutral theories of biodiversity and that an alternative family of generalized models provides a qualitatively better description. Together, these results lay the groundwork for a theoretical framework to connect ecological mechanisms to observed phylogenetic patterns in microbial communities. PMID:26106159

  11. Thermogelling Biodegradable Polymers with Hydrophilic Backbones: PEG-g-PLGA

    SciTech Connect

    Jeong, Byeongmoon; Kibbey, Merinda R.; Birnbaum, Jerome C.; Won, You-Yeong; Gutowska, Anna

    2000-10-31

    The aqueous solutions of poly(ethylene glycol)grafted with poly(lactic acid-co-glycolic acid) flow freely at room temperature but form gels at higher temperature. The existence of micelles in water at low polymer concentration was confirmed by Cro-transmission electron microscopy and dye solubilization studies. The micellar diameter and critical micelle concentration are about 9 nm and 0.47 wt.% respectively. The critical gel concentration, above which a gel phase appears was 16 wt.% and sol-to-gel transition temperature was slightly affected by the concentration in the range of 16 {approx} 25 wt.%. At sol-to-gel transition, viscosity increased abruptly and C-NMR showed molecular motion of hydrophilic poly(lactic acid-co-glycolic acid) side-chains increased. The hydrogel of PEG-g-PLGA with hydrophilic backbones was transparent during degradation and remained a gel for one week, suggesting a promising material for short-term drug delivery.

  12. Backbone Assignment of the MALT1 Paracaspase by Solution NMR

    PubMed Central

    Unnerståle, Sofia; Nowakowski, Michal; Baraznenok, Vera; Stenberg, Gun; Lindberg, Jimmy; Mayzel, Maxim; Orekhov, Vladislav; Agback, Tatiana

    2016-01-01

    Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a unique paracaspase protein whose protease activity mediates oncogenic NF-κB signalling in activated B cell-like diffuse large B cell lymphomas (ABC-DLBCLs). ABC-DLBCLs are aggressive lymphomas with high resistance to current chemotherapies. Low survival rate among patients emphasizes the urgent need for alternative treatment options. The characterization of the MALT1 will be an essential tool for developing new target-directed drugs against MALT1 dependent disorders. As the first step in the atomic-level NMR studies of the system, here we report, the 15N/13C/1H backbone assignment of the apo form of the MALT1 paracaspase region together with the third immunoglobulin-like (Ig3) domain, 44 kDa, by high resolution NMR. In addition, the non-uniform sampling (NUS) based targeted acquisition procedure is evaluated as a mean of decreasing acquisition and analysis time for larger proteins. PMID:26788853

  13. Solid state radiation chemistry of the DNA backbone

    SciTech Connect

    Bernhard, W.A.

    1989-09-01

    The long term goal of this program is to determine the fundamental rules needed to predict the type and yield of damage produced in DNA due to direct effects of ionizing radiation. The focus is on damage to the sugar-phosphate backbone, damage that would lead to strand breaks. Model systems have been chosen that permit various aspects of this problem to be investigated. The emphasis will be on single crystals of monosaccharides, nucleosides, and nucleotides but will also include some powder work on polynucleotides. In these model systems, free radical products and reactions are observed by electron spin resonance (ESR) and electron nuclear double resonance (ENDOR) techniques. The information thus gained is used in constructing rules that predict what primary free radicals are formed in single crystals of model compounds and the reactions stemming from the primary radicals. The formulation of a set of rules that work in model systems will represent a major advance toward formulating a set of rules that predict the direct damage in DNA itself. In a broader context this program is part of the effort to understand and predict the effects of exposure to ionizing radiation received at low dose rates over long periods of time. Assessment of low dose effects requires a basic understanding of the action of radiation at the molecular level. By contributing to that basic understanding, this program will help solve the problems of risk assessment under low dose conditions. 5 refs., 3 figs.

  14. Exocyclic groups in the minor groove influence the backbone conformation of DNA

    PubMed Central

    Wellenzohn, Bernd; Flader, Wolfgang; Winger, Rudolf H.; Hallbrucker, Andreas; Mayer, Erwin; Liedl, Klaus R.

    2001-01-01

    Exocyclic groups in the minor groove of DNA modulate the affinity and positioning of nucleic acids to the histone protein. The addition of exocyclic groups decreases the formation of this protein–DNA complex, while their removal increases nucleosome formation. On the other hand, recent theoretical results show a strong correlation between the BI/BII phosphate backbone conformation and the hydration of the grooves of the DNA. We performed a simulation of the d(CGCGAATTCGCG)2 Drew Dickerson dodecamer and one simulation of the d(CGCIAATTCGCG)2 dodecamer in order to investigate the influence of the exocyclic amino group of guanine. The removal of the amino group introduces a higher intrinsic flexibility to DNA supporting the suggestions that make the enhanced flexibility responsible for the enlarged histone complexation affinity. This effect is attributed to changes in the destacking interactions of both strands of the DNA. The differences in the hydration of the minor groove could be the explanation of this flexibility. The changed hydration of the minor groove also leads to a different BI/BII substate pattern. Due to the fact that the histone preferentially builds contacts with the backbone of the DNA, we propose an influence of these BI/BII changes on the nucleosome formation process. Thus, we provide an additional explanation for the enhanced affinity to the histone due to removal of exocyclic groups. In terms of BI/BII we are also able to explain how minor groove binding ligands could affect the nucleosome assembly without disrupting the structure of DNA. PMID:11812834

  15. Direct Observation of the Intrinsic Backbone Torsional Mobility of Disordered Proteins.

    PubMed

    Jain, Neha; Narang, Dominic; Bhasne, Karishma; Dalal, Vijit; Arya, Shruti; Bhattacharya, Mily; Mukhopadhyay, Samrat

    2016-08-23

    The fundamental backbone dynamics of unfolded proteins arising due to intrinsic ϕ-ψ dihedral angle fluctuations dictate the course of protein folding, binding, assembly, and function. These internal fluctuations are also critical for protein misfolding associated with a range of human diseases. However, direct observation and unambiguous assignment of this inherent dynamics in chemically denatured proteins is extremely challenging due to various experimental limitations. To directly map the backbone torsional mobility in the ϕ-ψ dihedral angle space, we used a model intrinsically disordered protein, namely, α-synuclein, that adopts an expanded state under native conditions. We took advantage of nonoccurrence of tryptophan in α-synuclein and created a number of single-tryptophan variants encompassing the entire polypeptide chain. We then utilized highly sensitive picosecond time-resolved fluorescence depolarization measurements that allowed us to discern the site-specific torsional relaxation at a low protein concentration under physiological conditions. For all the locations, the depolarization kinetics exhibited two well-separated rotational-correlation-time components. The shorter, subnanosecond component arises due to the local mobility of the indole side chain, whereas the longer rotational-correlation-time component (1.37 ± 0.15 ns), independent of global tumbling, represents a characteristic timescale for short-range conformational exchange in the ϕ-ψ dihedral space. This correlation time represents an intrinsic timescale for torsional relaxation and is independent of position, which is expected for an extended polypeptide chain having little or no propensity to form persistent structures. We were also able to capture this intrinsic timescale at the N-terminal unstructured domain of the prion protein. Our estimated timescale of the segmental mobility is similar to that of unfolded proteins studied by nuclear magnetic resonance in conjunction with

  16. Quantum chemical benchmark study on 46 RNA backbone families using a dinucleotide unit.

    PubMed

    Kruse, Holger; Mladek, Arnost; Gkionis, Konstantinos; Hansen, Andreas; Grimme, Stefan; Sponer, Jiri

    2015-10-13

    We have created a benchmark set of quantum chemical structure-energy data denoted as UpU46, which consists of 46 uracil dinucleotides (UpU), representing all known 46 RNA backbone conformational families. Penalty-function-based restrained optimizations with COSMO TPSS-D3/def2-TZVP ensure a balance between keeping the target conformation and geometry relaxation. The backbone geometries are close to the clustering-means of their respective RNA bioinformatics family classification. High-level wave function methods (DLPNO-CCSD(T) as reference) and a wide-range of dispersion-corrected or inclusive DFT methods (DFT-D3, VV10, LC-BOP-LRD, M06-2X, M11, and more) are used to evaluate the conformational energies. The results are compared to the Amber RNA bsc0χOL3 force field. Most dispersion-corrected DFT methods surpass the Amber force field significantly in accuracy and yield mean absolute deviations (MADs) for relative conformational energies of ∼0.4-0.6 kcal/mol. Double-hybrid density functionals represent the most accurate class of density functionals. Low-cost quantum chemical methods such as PM6-D3H+, HF-3c, DFTB3-D3, as well as small basis set calculations corrected for basis set superposition errors (BSSEs) by the gCP procedure are also tested. Unfortunately, the presently available low-cost methods are struggling to describe the UpU conformational energies with satisfactory accuracy. The UpU46 benchmark is an ideal test for benchmarking and development of fast methods to describe nucleic acids, including force fields. PMID:26574283

  17. Structure-guided unidirectional variation de-striping in the infrared bands of MODIS and hyperspectral images

    NASA Astrophysics Data System (ADS)

    Zhang, Yaozong; Zhang, Tianxu

    2016-07-01

    Images taken using moderate resolution imaging spectroradiometer (MODIS) and hyperspectral imaging systems, especially in their infrared bands, usually lead to undesired stripe noises, which seriously affect the image quality. A variational de-striping model has been proven to have good performance, but knowing how to detect stripes effectively, especially to distinguish them from edges/textures, is still challenging. In this paper, a structure-guided unidirectional variational (SGUV) model that considers the structure of stripes is proposed. Because of the use of structure information, which textures and edges do not have, the proposed algorithm can effectively distinguish stripes from image textures and almost does not blur details while removing stripes. Comparative experiments based on real stripe images demonstrated that the proposed method provides optimal qualitative and quantitative results.

  18. Small-scale variations in the galactic magnetic field - The rotation measure structure function and birefringence in interstellar scintillations

    NASA Technical Reports Server (NTRS)

    Simonetti, J. H.; Cordes, J. M.; Spangler, S. R.

    1984-01-01

    The structure function of rotation measures of extragalactic sources and birefringence in interstellar scintillations are used to investigate variations in the interstellar magnetic field on length scales of about 0.01-100 pc and 10 to the 11th cm, respectively. Model structure functions are derived for the case of a power-law power spectrum of irregularities in the quantity (n(e)B), and an estimate for the structure function is computed for several regions of the sky using data on extragalactic sources. The results indicate an outer angular scale for rotation measure (RM) variations of not less than about 5 deg (a linear scale of about 9-90 pc at a distance of 0.1-1 kpc). There is also evidence for RM variations on angular scales as small as 1 arcmin, but it cannot be determined whether these are intrinsic to the source or caused by the interstellar medium. The effect of a random, Faraday-active medium on the diffraction of radio waves is derived, and an upper limit to the variations in n(e)B on a length scale of 10 to the 11th cm is obtained from available observations.

  19. Emergent structured transition from variation to repetition in a biologically-pl