Science.gov

Sample records for linker substructure common

  1. Common substructure in otoacoustic emission spectra of land vertebrates

    NASA Astrophysics Data System (ADS)

    Manley, Geoffrey A.; Köppl, Christine; Bergevin, Christopher

    2015-12-01

    In humans, a similar spectral periodicity is found in all otoacoustic emission types and in threshold fine structure. This may reflect travelling wave phase and reflectance from "structural roughness" in the organ of Corti, or entrainment and suppressive interactions between emissions. To further understand these phenomena, we have examined spontaneous otoacoustic emission (SOAE) spectra in 9 lizard species and the barn owl and find a comparable periodicity. Importantly, the frequency spacing between SOAE peaks was independent of the physical spacing and of the frequency space constants in hearing organs. In 9 lizard species, median spectral gaps lay between 219 and 461 Hz, with no correlation to papillar length (0.3 to 2.1 mm). Similarly in much longer organs: In humans (35 mm), SOAE spectral gaps vary up to 220 Hz at 4 kHz; in the barn owl (11 mm), the median SOAE peak spacing was 395Hz. In the barn owl, a very large space constant between 5 and 10 kHz (5 mm/octave) contrasts with stable SOAE spacing between 1 and 11 kHz. Similar SOAE spectral gaps across all species suggests they represent a basic frequency grating revealing local phase-dependent interactions between active hair cells, a feature not determined by macro-structural anatomy. Emission spectral spacing is independent of cochlear length, of the frequency space constant, of the existence of travelling waves or of a tectorial membrane. Our data suggest that there are greater similarities between frequency selectivity reflected at the level of the hair cells' spontaneous mechanical output (OAEs) than there are at the level of the auditory nerve, where macro-structural anatomy links hair-cell activity differentially to the neural output. Apparently, all hair-cell arrays show a similar frequency substructure not directly replicated in neural tuning.

  2. Design of chemical space networks using a Tanimoto similarity variant based upon maximum common substructures.

    PubMed

    Zhang, Bijun; Vogt, Martin; Maggiora, Gerald M; Bajorath, Jürgen

    2015-10-01

    Chemical space networks (CSNs) have recently been introduced as an alternative to other coordinate-free and coordinate-based chemical space representations. In CSNs, nodes represent compounds and edges pairwise similarity relationships. In addition, nodes are annotated with compound property information such as biological activity. CSNs have been applied to view biologically relevant chemical space in comparison to random chemical space samples and found to display well-resolved topologies at low edge density levels. The way in which molecular similarity relationships are assessed is an important determinant of CSN topology. Previous CSN versions were based on numerical similarity functions or the assessment of substructure-based similarity. Herein, we report a new CSN design that is based upon combined numerical and substructure similarity evaluation. This has been facilitated by calculating numerical similarity values on the basis of maximum common substructures (MCSs) of compounds, leading to the introduction of MCS-based CSNs (MCS-CSNs). This CSN design combines advantages of continuous numerical similarity functions with a robust and chemically intuitive substructure-based assessment. Compared to earlier version of CSNs, MCS-CSNs are characterized by a further improved organization of local compound communities as exemplified by the delineation of drug-like subspaces in regions of biologically relevant chemical space.

  3. The optimization of running time for a maximum common substructure-based algorithm and its application in drug design.

    PubMed

    Chen, Jian; Sheng, Jia; Lv, Dijing; Zhong, Yang; Zhang, Guoqing; Nan, Peng

    2014-02-01

    In the field of drug discovery, it is particularly important to discover bioactive compounds through high-throughput virtual screening. The maximum common substructure-based (MCS) algorithm is a promising method for the virtual screening of drug candidates. However, in practical applications, there is always a trade-off between efficiency and accuracy. In this paper, we optimized this method by running time evaluation using essential drugs defined by WHO and FDA-approved small-molecule drugs. The amount of running time allocated to the MCS-based virtual screening was varied, and statistical analysis was conducted to study the impact of computation running time on the screening results. It was determined that the running time efficiency can be improved without compromising accuracy by setting proper running time thresholds. In addition, the similarity of compound structures and its relevance to biological activity are analyzed quantitatively, which highlight the applicability of the MCS-based methods in predicting functions of small molecules. 15-30s was established as a reasonable range for selecting a candidate running time threshold. The effect of CPU speed is considered and the conclusion is generalized. The potential biological activity of small molecules with unknown functions can be predicted by the MCS-based methods.

  4. Discovering Substructure in Examples

    DTIC Science & Technology

    1988-05-01

    the gestalt motivation for the previouslv discussed heuristics, gestalt theory suggests many additional 16 %0 [ ’ , factors identified in human...to substructure discovery. Gestalt theory motivates several of the ideas behind the substructure discovery algorithm. In the area of machine learning...5.1. Gestalt Psychology Many of the ideas in this thesis originated from work in gestalt psychology [Kohler47]. Gestalt theory identifies several

  5. The wave-based substructuring approach for the efficient description of interface dynamics in substructuring

    NASA Astrophysics Data System (ADS)

    Donders, S.; Pluymers, B.; Ragnarsson, P.; Hadjit, R.; Desmet, W.

    2010-04-01

    In the vehicle design process, design decisions are more and more based on virtual prototypes. Due to competitive and regulatory pressure, vehicle manufacturers are forced to improve product quality, to reduce time-to-market and to launch an increasing number of design variants on the global market. To speed up the design iteration process, substructuring and component mode synthesis (CMS) methods are commonly used, involving the analysis of substructure models and the synthesis of the substructure analysis results. Substructuring and CMS enable efficient decentralized collaboration across departments and allow to benefit from the availability of parallel computing environments. However, traditional CMS methods become prohibitively inefficient when substructures are coupled along large interfaces, i.e. with a large number of degrees of freedom (DOFs) at the interface between substructures. The reason is that the analysis of substructures involves the calculation of a number of enrichment vectors, one for each interface degree of freedom (DOF). Since large interfaces are common in vehicles (e.g. the continuous line connections to connect the body with the windshield, roof or floor), this interface bottleneck poses a clear limitation in the vehicle noise, vibration and harshness (NVH) design process. Therefore there is a need to describe the interface dynamics more efficiently. This paper presents a wave-based substructuring (WBS) approach, which allows reducing the interface representation between substructures in an assembly by expressing the interface DOFs in terms of a limited set of basis functions ("waves"). As the number of basis functions can be much lower than the number of interface DOFs, this greatly facilitates the substructure analysis procedure and results in faster design predictions. The waves are calculated once from a full nominal assembly analysis, but these nominal waves can be re-used for the assembly of modified components. The WBS approach thus

  6. Substructure of the outer dynein arm

    PubMed Central

    1982-01-01

    The substructure of the outer dynein arm has been analyzed in quick- frozen deep-etch replicas of Tetrahymena and Chlamydomonas axonemes. Each arm is found to be composed of five morphologically discrete components: an elliptical head; two spherical feet; a slender stalk; and an interdynein linker. The feet make contact with the A microtubule of each doublet; the stalk contacts the B microtubule; the head lies between the feet and stalk; and the linker associates each arm with its neighbor. The spatial relationships between these five components are found to be distinctly different in rigor (ATP-depleted) versus relaxed (ATP- or vanadate plus ATP-treated) axonemes, and the stalk appears to alter its affinity for the B microtubule in the relaxed state. Images of living cilia attached to Tetrahymena cells show that the relaxed configuration is adopted in vivo. We relate our observations to morphological and experimental studies reported by others and propose several models that suggest how this newly described dynein morphology may relate to dynein function. PMID:6218174

  7. Chapter 6: Energy Storage in Cellulase Linker Peptides?

    SciTech Connect

    McCabe, C.; Zhao, X.; Adney, W. S.; Himmel, M. E.

    2010-01-01

    In this chapter, we discuss the use of molecular dynamics simulations and free-energy calculations to investigate the possible role the linker polypeptide, common to many cellulase enzymes, plays in the enzymatic hydrolysis of cellulose. In particular, we focus on the linker polypeptide from cellobiohydrolase I (CBH I) from Trichoderma reesei, which is one of the most active cellulase enzymes. CBH I is a multi-domain enzyme, consisting of a large catalytic domain containing an active site tunnel and a small cellulose binding module, which are joined together by a 27-amino-acid residue linker peptide. CBH I is believed to hydrolyze cellulose in a 'processive' manner; however, the exact mechanism of the depolymerization of cellulose by CBH I is not fully understood. It has been hypothesized that the flexible interdomain linker mediates a caterpillar-like motion that enables the enzyme to move along the cellodextrin strand. Although the linker polypeptide sequence is known, the spatial conformation adopted by the linker domain and its role in the hydrolysis process, if any, has yet to be determined. The simulation results obtained to date indicate that the CBH I linker's free energy is critically dependent on the existence of the cellulose substrate and the stretching/compression pathway adopted. In the presence of a cellulose surface, simulations suggest that the linker exhibits two stable states, which would support the hypothesis that the linker peptide has the capacity to store energy in a manner similar to a spring and facilitate a caterpillar-like motion.

  8. A new interface element for connecting independently modeled substructures

    NASA Technical Reports Server (NTRS)

    Ransom, Jonathan B.; Mccleary, Susan L.; Aminpour, Mohammad A.

    1993-01-01

    A new interface element based on the hybrid variational formulation is presented and demonstrated. The element provides a means of connecting independently modeled substructures whose nodes along the common boundary need not be coincident. The interface element extends previous work to include connecting an arbitrary number of substructures, the use of closed and generally curved interfaces, and the use of multiple, possibly nested, interfaces. Several applications of the element are presented and aspects of the implementation are discussed.

  9. Cluster X-Ray Substructure and Radio Galaxy Correlations

    NASA Astrophysics Data System (ADS)

    Ledlow, M. J.; Burns, J. O.

    1994-12-01

    Current wisdom suggests that X-ray substructure in the intracluster medium (ICM) is fairly common in galaxy clusters. This substructure takes the form of elongations, isophotal twisting, asymmetries, and sub-clumping. Substructure is also frequently present in kinematical analysis of the galaxy velocity and spatial distributions. These features include bimodality, kurtosis or skewness, and non-Gaussian velocity distributions. Consistent with the observations, Hydro/N-Body simulations suggest that cluster-subcluster mergers may be the culprit to explain these features in the ICM gas distribution, and would indicate that many clusters, even at the present epoch, are still undergoing significant dynamical evolution. From a sample of X-ray images from the Einstein satellite and, more recently, the ROSAT mission, Burns et al. (1994) found a significant correlation between the positions of radio galaxies and subclumps within the cluster-scale X-ray emission. Burns et al. have suggested that radio galaxies reside in the residue of cluster/sub-cluster merging sites, and may therefore act as pointers to clusters with ongoing and intersting dynamical activity. We are following up these ideas with a detailed substructure analysis, and a comparison to a sample of clusters without radio galaxies. In order to determine the signficance of substructure, we have reanalyzed the X-ray images using a Bootstrap-Resampling Monte-Carlo technique. In this method, asymmetries, elongations, and other forms of substructure are evaluated using a moment-analysis similar to M{o}hr et al. (1994), with the advantage that we need not assume apriori any specific substructure-free model for the source (\\ie\\ a Beta-model). The significance of individual features is determined solely from a comparison to statistical fluctuations (including noise) of the actual data. Using this technique, we place limits on the fraction of clusters with significant substructure and test the radio galaxy/substructure

  10. Proposed definition of crystal substructure and substructural similarity

    NASA Astrophysics Data System (ADS)

    Yang, Lusann; Dacek, Stephen; Ceder, Gerbrand

    2014-08-01

    There is a clear need for a practical and mathematically rigorous description of local structure in inorganic compounds so that structures and chemistries can be easily compared across large data sets. Here a method for decomposing crystal structures into substructures is given, and a similarity function between those substructures is defined. The similarity function is based on both geometric and chemical similarity. This construction allows for large-scale data mining of substructural properties, and the analysis of substructures and void spaces within crystal structures. The method is validated via the prediction of Li-ion intercalation sites for the oxides. Tested on databases of known Li-ion-containing oxides, the method reproduces all Li-ion sites in an oxide with a maximum of 4 incorrect guesses 80% of the time.

  11. Linker DNA destabilizes condensed chromatin.

    PubMed

    Green, G R; Ferlita, R R; Walkenhorst, W F; Poccia, D L

    2001-01-01

    The contribution of the linker region to maintenance of condensed chromatin was examined in two model systems, namely sea urchin sperm nuclei and chicken red blood cell nuclei. Linkerless nuclei, prepared by extensive digestion with micrococcal nuclease, were compared with Native nuclei using several assays, including microscopic appearance, nuclear turbidity, salt stability, and trypsin resistance. Chromatin in the Linkerless nuclei was highly condensed, resembling pyknotic chromatin in apoptotic cells. Linkerless nuclei were more stable in low ionic strength buffers and more resistant to trypsin than Native nuclei. Analysis of histones from the trypsinized nuclei by polyacrylamide gel electrophoresis showed that specific histone H1, H2B, and H3 tail regions stabilized linker DNA in condensed nuclei. Thermal denaturation of soluble chromatin preparations from differentially trypsinized sperm nuclei demonstrated that the N-terminal regions of histones Sp H1, Sp H2B, and H3 bind tightly to linker DNA, causing it to denature at a high temperature. We conclude that linker DNA exerts a disruptive force on condensed chromatin structure which is counteracted by binding of specific histone tail regions to the linker DNA. The inherent instability of the linker region may be significant in all eukaryotic chromatins and may promote gene activation in living cells.

  12. NASTRAN GPWG tables for combined substructures

    NASA Technical Reports Server (NTRS)

    Allen, Tom

    1991-01-01

    A method for computing the mass and center of gravity for basic and combined substructures stored in the NASTRAN Substructure Operating File (SOF) is described. The three step method recovers SOF data blocks for the relevant substructure, processes these data blocks using a specially developed FORTRAN routine, and generates the NASTRAN gridpoint weight generator (GPWG) table for the substructure in a PHASE2 SOF execution using a Direct Matrix Abstraction Program (DMAP) sequence. Verification data for the process is also provided.

  13. Microstructure versus substructure size effect

    NASA Astrophysics Data System (ADS)

    Ghassemali, Ehsan; Jarfors, Anders E. W.; Tan, Ming-Jen; Wah, Chua Beng

    2016-10-01

    In metal deformation, size effect is generally attributed to the interactive effect of grain size and specimen dimension. This work shows, however, that relative substructure dimensions should also be considered. Micro-compression tests on the micro-pins having different grain sizes revealed no significant size effect with respect to the mechanical behavior, even if the number of grains over the diameter of the micro-pins falls below its critical value. To justify the reason laying under this fact, a recovery annealing cycle was applied on the micro-pins to change the substructure properties without altering the mean grain size. A surprising drop in the flow stress of the recovery-annealed micro-pins implied the importance of considering subgrain size rather than grain size over the diameter of component for the size effect investigation.

  14. Substructure mining using elaborate chemical representation.

    PubMed

    Kazius, Jeroen; Nijssen, Siegfried; Kok, Joost; Bäck, Thomas; Ijzerman, Adriaan P

    2006-01-01

    Substructure mining algorithms are important drug discovery tools since they can find substructures that affect physicochemical and biological properties. Current methods, however, only consider a part of all chemical information that is present within a data set of compounds. Therefore, the overall aim of our study was to enable more exhaustive data mining by designing methods that detect all substructures of any size, shape, and level of chemical detail. A means of chemical representation was developed that uses atomic hierarchies, thus enabling substructure mining to consider general and/or highly specific features. As a proof-of-concept, the efficient, multipurpose graph mining system Gaston learned substructures of any size and shape from a mutagenicity data set that was represented in this manner. From these substructures, we extracted a set of only six nonredundant, discriminative substructures that represent relevant biochemical knowledge. Our results demonstrate the individual and synergistic importance of elaborate chemical representation and mining for nonlinear substructures. We conclude that the combination of elaborate chemical representation and Gaston provides an excellent method for 2D substructure mining as this recipe systematically explores all substructures in different levels of chemical detail.

  15. Chemical substructure analysis in toxicology

    SciTech Connect

    Beauchamp, R.O. Jr.

    1990-12-31

    A preliminary examination of chemical-substructure analysis (CSA) demonstrates the effective use of the Chemical Abstracts compound connectivity file in conjunction with the bibliographic file for relating chemical structures to biological activity. The importance of considering the role of metabolic intermediates under a variety of conditions is illustrated, suggesting structures that should be examined that may exhibit potential activity. This CSA technique, which utilizes existing large files accessible with online personal computers, is recommended for use as another tool in examining chemicals in drugs. 2 refs., 4 figs.

  16. MASS SUBSTRUCTURE IN ABELL 3128

    SciTech Connect

    McCleary, J.; Dell’Antonio, I.; Huwe, P.

    2015-05-20

    We perform a detailed two-dimensional weak gravitational lensing analysis of the nearby (z = 0.058) galaxy cluster Abell 3128 using deep ugrz imaging from the Dark Energy Camera (DECam). We have designed a pipeline to remove instrumental artifacts from DECam images and stack multiple dithered observations without inducing a spurious ellipticity signal. We develop a new technique to characterize the spatial variation of the point-spread function that enables us to circularize the field to better than 0.5% and thereby extract the intrinsic galaxy ellipticities. By fitting photometric redshifts to sources in the observation, we are able to select a sample of background galaxies for weak-lensing analysis free from low-redshift contaminants. Photometric redshifts are also used to select a high-redshift galaxy subsample with which we successfully isolate the signal from an interloping z = 0.44 cluster. We estimate the total mass of Abell 3128 by fitting the tangential ellipticity of background galaxies with the weak-lensing shear profile of a Navarro–Frenk–White (NFW) halo and also perform NFW fits to substructures detected in the 2D mass maps of the cluster. This study yields one of the highest resolution mass maps of a low-z cluster to date and is the first step in a larger effort to characterize the redshift evolution of mass substructures in clusters.

  17. Commonality.

    ERIC Educational Resources Information Center

    Beaton, Albert E., Jr.

    Commonality analysis is an attempt to understand the relative predictive power of the regressor variables, both individually and in combination. The squared multiple correlation is broken up into elements assigned to each individual regressor and to each possible combination of regressors. The elements have the property that the appropriate sums…

  18. Parallel Computational Environment for Substructure Optimization

    NASA Technical Reports Server (NTRS)

    Gendy, Atef S.; Patnaik, Surya N.; Hopkins, Dale A.; Berke, Laszlo

    1995-01-01

    Design optimization of large structural systems can be attempted through a substructure strategy when convergence difficulties are encountered. When this strategy is used, the large structure is divided into several smaller substructures and a subproblem is defined for each substructure. The solution of the large optimization problem can be obtained iteratively through repeated solutions of the modest subproblems. Substructure strategies, in sequential as well as in parallel computational modes on a Cray YMP multiprocessor computer, have been incorporated in the optimization test bed CometBoards. CometBoards is an acronym for Comparative Evaluation Test Bed of Optimization and Analysis Routines for Design of Structures. Three issues, intensive computation, convergence of the iterative process, and analytically superior optimum, were addressed in the implementation of substructure optimization into CometBoards. Coupling between subproblems as well as local and global constraint grouping are essential for convergence of the iterative process. The substructure strategy can produce an analytically superior optimum different from what can be obtained by regular optimization. For the problems solved, substructure optimization in a parallel computational mode made effective use of all assigned processors.

  19. Substructure Main Bridge, Piers B & C Huey ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Substructure - Main Bridge, Piers B & C - Huey P. Long Bridge, Spanning Mississippi River approximately midway between nine & twelve mile points upstream from & west of New Orleans, Jefferson, Jefferson Parish, LA

  20. Chemical substructure search in SQL.

    PubMed

    Golovin, Adel; Henrick, Kim

    2009-01-01

    We present a novel technique for a fast chemical substructure search on a relational database by use of a standard SQL query. The symmetry of a query graph is analyzed to give additional constraints. Our method is based on breadth-first search (BFS) algorithms implementation using Relational Database Management Systems (RDBMS). In addition to the chemical search we apply our technique to the field of intermolecular interactions which involves nonplanar graphs and describe how to achieve linear time performance along with the suggestion on how to sufficiently reduce the linear coefficient. From the algorithms theory perspective these results mean that subgraph isomorphism is a polynomial time problem, hence equal problems have the same complexity. The application to subgraph isomorphism in chemical search is available at http://www.ebi.ac.uk/msd-srv/chemsearch and http://www.ebi.ac.uk/msd-srv/msdmotif/chem . The application to the network of molecule interactions is available at http://www.ebi.ac.uk/msd-srv/msdmotif .

  1. Substructure-based control of flexible structures

    NASA Astrophysics Data System (ADS)

    Babuska, Vit

    The desire to build large space structures has motivated research into the problem of flexible structure control. In general, the controllers for these structures can be designed using a centralized strategy or a decentralized strategy. In the centralized approach, the controller is based on a model of the complete structure. In the decentralized approach, the structure model is decomposed into subsystems for which controllers are designed, and then these subsystem controllers are combined to control the complete structure. The subsystems can be mathematical constructs such as groups of modes, or physical subsystems like substructures. This dissertation examines substructure-based decentralized design of controllers for flexible structures. Three different, but related, topics are discussed in this work. First, a relationship is shown to exist between the substructural controller synthesis (SCS) method of designing active controllers for flexible structures and decentralized control using overlapping information sets. It is shown that, in the case of full-state feedback, the SCS method is a specific case of decentralized control using overlapping subsystems. In the case of dynamic output feedback (e.g., LQG controllers), the SCS method departs from standard decentralized control techniques. The controllers are 'assembled' by extending the concept of substructural assembly to general linear systems. Next, a new design method is proposed which combines the concept of component mode synthesis (CMS) with control theory in a decentralized method for the design of controllers for flexible structures. This method, called the augmented physical component synthesis (APCS) method, creates augmented substructural components. These components are substructures whose boundaries are loaded with some dynamics of the adjacent substructures. This allows global control objectives such as line-of-sight error minimization to be met with a substructure-based design strategy. Finally

  2. Algebraic Sub-Structuring for Electromagnetic Applications

    SciTech Connect

    Yang, C.; Gao, W.G.; Bai, Z.J.; Li, X.Y.S.; Lee, L.Q.; Husbands, P.; Ng, E.G.; /LBL, Berkeley /UC, Davis /SLAC

    2006-06-30

    Algebraic sub-structuring refers to the process of applying matrix reordering and partitioning algorithms to divide a large sparse matrix into smaller submatrices from which a subset of spectral components are extracted and combined to form approximate solutions to the original problem. In this paper, they show that algebraic sub-structuring can be effectively used to solve generalized eigenvalue problems arising from the finite element analysis of an accelerator structure.

  3. Algebraic sub-structuring for electromagnetic applications

    SciTech Connect

    Yang, Chao; Gao, Weiguo; Bai, Zhaojun; Li, Xiaoye; Lee, Lie-Quan; Husbands, Parry; Ng, Esmond G.

    2004-09-14

    Algebraic sub-structuring refers to the process of applying matrix reordering and partitioning algorithms to divide a large sparse matrix into smaller submatrices from which a subset of spectral components are extracted and combined to form approximate solutions to the original problem. In this paper, we show that algebraic sub-structuring can be effectively used to solve generalized eigenvalue problems arising from the finite element analysis of an accelerator structure.

  4. A structural design decomposition method utilizing substructuring

    NASA Technical Reports Server (NTRS)

    Scotti, Stephen J.

    1994-01-01

    A new method of design decomposition for structural analysis and optimization is described. For this method, the structure is divided into substructures where each substructure has its structural response described by a structural-response subproblem, and its structural sizing determined from a structural-sizing subproblem. The structural responses of substructures that have rigid body modes when separated from the remainder of the structure are further decomposed into displacements that have no rigid body components, and a set of rigid body modes. The structural-response subproblems are linked together through forces determined within a structural-sizing coordination subproblem which also determines the magnitude of any rigid body displacements. Structural-sizing subproblems having constraints local to the substructures are linked together through penalty terms that are determined by a structural-sizing coordination subproblem. All the substructure structural-response subproblems are totally decoupled from each other, as are all the substructure structural-sizing subproblems, thus there is significant potential for use of parallel solution methods for these subproblems.

  5. Initial conformation of kinesin's neck linker

    NASA Astrophysics Data System (ADS)

    Geng, Yi-Zhao; Ji, Qing; Liu, Shu-Xia; Yan, Shi-Wei

    2014-10-01

    How ATP binding initiates the docking process of kinesin's neck linker is a key question in understanding kinesin mechanisms. By exploiting a molecular dynamics method, we investigate the initial conformation of kinesin's neck linker in its docking process. We find that, in the initial conformation, the neck linker has interactions with β0 and forms a ‘cover-neck bundle’ structure with β0. From this initial structure, the formation of extra turns and the docking of the cover-neck bundle structure can be achieved. The motor head provides a forward force on the initial cover-neck bundle structure through ATP-induced rotation. This force, together with the hydrophobic interaction of ILE327 with the hydrophobic pocket on the motor head, drives the formation of the extra turn and initiates the neck linker docking process. Based on these findings, a pathway from ATP binding-induced motor head rotation to neck linker docking is proposed.

  6. Unfolding a linker between helical repeats.

    PubMed

    Ortiz, Vanessa; Nielsen, Steven O; Klein, Michael L; Discher, Dennis E

    2005-06-10

    In many multi-repeat proteins, linkers between repeats have little secondary structure and place few constraints on folding or unfolding. However, the large family of spectrin-like proteins, including alpha-actinin, spectrin, and dystrophin, share three-helix bundle, spectrin repeats that appear in crystal structures to be linked by long helices. All of these proteins are regularly subjected to mechanical stress. Recent single molecule atomic force microscopy (AFM) experiments demonstrate not only forced unfolding but also simultaneous unfolding of tandem repeats at finite frequency, which suggests that the contiguous helix between spectrin repeats can propagate a cooperative helix-to-coil transition. Here, we address what happens atomistically to the linker under stress by steered molecular dynamics simulations of tandem spectrin repeats in explicit water. The results for alpha-actinin repeats reveal rate-dependent pathways, with one pathway showing that the linker between repeats unfolds, which may explain the single-repeat unfolding pathway observed in AFM experiments. A second pathway preserves the structural integrity of the linker, which explains the tandem-repeat unfolding event. Unfolding of the linker begins with a splay distortion of proximal loops away from hydrophobic contacts with the linker. This is followed by linker destabilization and unwinding with increased hydration of the backbone. The end result is an unfolded helix that mechanically decouples tandem repeats. Molecularly detailed insights obtained here aid in understanding the mechanical coupling of domain stability in spectrin family proteins.

  7. DNA Linker Mediated Assembly of Colloidal Nanoparticles

    NASA Astrophysics Data System (ADS)

    Xiong, Huiming; van der Lelie, Daniel; Gang, Oleg

    2009-03-01

    When flexible ssDNA linkers are added to the mixture of two types of dispersed, ssDNAs capped gold nanocolloids which are mutually non-complementary but complementary to the respective ends of the linker DNA, a crystalline phase of body-centered-cubic unit cell forms. The phase diagram of DNA linker mediated nanoparticle assemblies has been experimentally investigated and constructed by using in-situ small angle x-ray scattering. The influence of linkage defects on crystalline structure was also examined.

  8. Singular behavior of jet substructure observables

    DOE PAGES

    Larkoski, Andrew J.; Moult, Ian

    2016-01-20

    Jet substructure observables play a central role at the Large Hadron Collider for identifying the boosted hadronic decay products of electroweak scale resonances. The complete description of these observables requires understanding both the limit in which hard substructure is resolved, as well as the limit of a jet with a single hard core. In this paper we study in detail the perturbative structure of two prominent jet substructure observables, N-subjettiness and the energy correlation functions, as measured on background QCD jets. In particular, we focus on the distinction between the limits in which two-prong structure is resolved or unresolved. Dependingmore » on the choice of subjet axes, we demonstrate that at fixed order, N-subjettiness can manifest myriad behaviors in the unresolved region: smooth tails, end-point singularities, or singularities in the physical region. The energy correlation functions, by contrast, only have non-singular perturbative tails extending to the end point. We discuss the effect of hadronization on the various observables with Monte Carlo simulation and demonstrate that the modeling of these effects with non-perturbative shape functions is highly dependent on the N-subjettiness axes definitions. Lastly, our study illustrates those regions of phase space that must be controlled for high-precision jet substructure calculations, and emphasizes how such calculations can be facilitated by designing substructure observables with simple singular structures.« less

  9. Singular behavior of jet substructure observables

    SciTech Connect

    Larkoski, Andrew J.; Moult, Ian

    2016-01-20

    Jet substructure observables play a central role at the Large Hadron Collider for identifying the boosted hadronic decay products of electroweak scale resonances. The complete description of these observables requires understanding both the limit in which hard substructure is resolved, as well as the limit of a jet with a single hard core. In this paper we study in detail the perturbative structure of two prominent jet substructure observables, N-subjettiness and the energy correlation functions, as measured on background QCD jets. In particular, we focus on the distinction between the limits in which two-prong structure is resolved or unresolved. Depending on the choice of subjet axes, we demonstrate that at fixed order, N-subjettiness can manifest myriad behaviors in the unresolved region: smooth tails, end-point singularities, or singularities in the physical region. The energy correlation functions, by contrast, only have non-singular perturbative tails extending to the end point. We discuss the effect of hadronization on the various observables with Monte Carlo simulation and demonstrate that the modeling of these effects with non-perturbative shape functions is highly dependent on the N-subjettiness axes definitions. Lastly, our study illustrates those regions of phase space that must be controlled for high-precision jet substructure calculations, and emphasizes how such calculations can be facilitated by designing substructure observables with simple singular structures.

  10. Flexible non-nucleotide linkers as loop replacements in short double helical RNAs

    PubMed Central

    Pils, Werner; Micura, Ronald

    2000-01-01

    Ethylene glycol oligomers have been studied systematically as non-nucleotide loop replacements in short hairpin oligoribonucleotides. Structural optimization concerns the length of the linkers and is based on the thermodynamic stabilities of the corresponding duplexes. The optimum linker is derived from heptakis (ethylene glycol) provided that the duplex end to be bridged comprises solely the terminal base pair; the optimum linker is derived from hexakis(ethylene glycol) if a dangling unpaired nucleotide is incorporated into the loop. Moreover, these linkers have been compared to other commonly used linker types which consist of repeating units of tris- or tetrakis(ethylene glycol) phosphate, or of 3-hydroxypropane-1-phosphate. In all cases, the correlation between linker length and duplex stability is independent of the kind of counter ions used (Na+, Na+/Mg2+, K+ or Li+). Furthermore, all duplexes with non-nucleotide loop replacements are less stable than those with the corresponding standard nucleotide loop. The results corroborate that the linkers are solvent-exposed and do not specifically interfere with the terminal nucleotides at the bridged duplex end. PMID:10756183

  11. Hydroquinone–pyrrole dyads with varied linkers

    PubMed Central

    Huang, Hao; Karlsson, Christoffer; Strømme, Maria; Sjödin, Martin

    2016-01-01

    Summary A series of pyrroles functionalized in the 3-position with p-dimethoxybenzene via various linkers (CH2, CH2CH2, CH=CH, C≡C) has been synthesized. Their electronic properties have been deduced from 1H NMR, 13C NMR, and UV–vis spectra to detect possible interactions between the two aromatic subunits. The extent of conjugation between the subunits is largely controlled by the nature of the linker, with the largest conjugation found with the trans-ethene linker and the weakest with the aliphatic linkers. DFT calculations revealed substantial changes in the HOMO–LUMO gap that correlated with the extent of conjugation found experimentally. The results of this work are expected to open up for use of the investigated compounds as components of redox-active materials in sustainable, organic electrical energy storage devices. PMID:26877811

  12. Structure and Functions of Linker Histones.

    PubMed

    Lyubitelev, A V; Nikitin, D V; Shaytan, A K; Studitsky, V M; Kirpichnikov, M P

    2016-03-01

    Linker histones such as variants H1, H5, and other similar proteins play an important role in regulation of chromatin structure and dynamics. However, interactions of linker histones with DNA and proteins, as well as specific functions of their different variants, are poorly studied. This is because they acquire tertiary structure only when interacting with a nucleosome, and because of limitations of currently available methods. However, deeper investigation of linker histones and their interactions with other proteins will address a number of important questions - from structure of compacted chromatin to regulation of early embryogenesis. In this review, structures of histone H1 variants and its interaction with chromatin DNA are considered. A possible functional significance of different H1 variants, a role of these proteins in maintaining interphase chromatin structure, and interactions of linker histones with other cellular proteins are also discussed.

  13. Particel substructure. A common theme of discovery in this century

    SciTech Connect

    Panofsky, W.K.H.

    1984-02-01

    Some example of modern developments in particel physics are given which demonstrate that the fundamental rules of quantum mechanics, applied to all forces in nature as they became understood, have retained their validity. The well-established laws of electricity and magnetism, reformulated in terms of quantum mechanics, have exhibited a truly remarkable numerical agreement between theory and experiment over an enormous range of observation. As experimental techniques have grown from the top of a laboratory bench to the large accelerators of today, the basic components of experimentation have changed vastly in scale but only little in basic function. More important, the motivation of those engaged in this type of experimentation has hardly changed at all.

  14. Particle Substructure. A Common Theme of Discovery in this Century

    DOE R&D Accomplishments Database

    Panofsky, W. K. H.

    1984-02-01

    Some example of modern developments in particle physics are given which demonstrate that the fundamental rules of quantum mechanics, applied to all forces in nature as they became understood, have retained their validity. The well-established laws of electricity and magnetism, reformulated in terms of quantum mechanics, have exhibited a truly remarkable numerical agreement between theory and experiment over an enormous range of observation. As experimental techniques have grown from the top of a laboratory bench to the large accelerators of today, the basic components of experimentation have changed vastly in scale but only little in basic function. More important, the motivation of those engaged in this type of experimentation has hardly changed at all.

  15. DNA Linker-Mediated Crystallization of Nanocolloids

    SciTech Connect

    Xiong,H.; van der Lelie, D.; Gang, L.

    2008-01-01

    Biofunctionalized nanocolloids offer a promising platform for creation of novel materials using addressable interactions. Crystalline phases are of especial interest for the development of novel plasmonic, magnetic, and catalytic metamaterials. When flexible single-stranded linker DNAs are added to the mixture of two types of dispersed, ssDNAs capped gold nanocolloids which are noncomplementary to each other but complementary to the respective ends of the linker DNA, a crystalline phase of body-centered cubic unit cell is formed at the premelting temperature of the system. An evolution of the structure, crystal formation, and thermodynamic path toward equilibrium state have been studied in details using in-situ small-angle X-ray scattering for different DNA linker designs.

  16. DNA Linker Mediated Crystallization of Nanocolloids

    NASA Astrophysics Data System (ADS)

    Xiong, Huiming; van der Lelie, Daniel; Gang, Oleg

    2008-03-01

    Biofunctionalized nanocolloids offer a promising platform for creation of novel materials using bio-addressable interactions. Crystalline phases are of especial interest for the development of novel functional structures. We demonstrate that crystallization of nanocolloids can be achieved via hybridization of dispersed non-complementary single stranded DNA capped colloids with flexible single-stranded linker DNA. The crystalline structure belongs to body central cubic lattice and exhibits large thermal expansion. The evolution of the structure has been studied in details using in-situ small angle x-ray scattering. The formation of crystalline structures and reduced metastability are observed for systems with longer DNA linkers.

  17. Linker histones: History and current perspectives.

    PubMed

    Crane-Robinson, C

    2016-03-01

    Although the overall structure of the fifth histone (linker histone, H1) is understood, its location on the nucleosome is only partially defined. Whilst it is clear that H1 helps condense the chromatin fibre, precisely how this is achieved remains to be determined. H1 is not a general gene repressor in that although it must be displaced from transcription start sites for activity to occur, there is only partial loss along the body of genes. How the deposition and removal of H1 occurs in particular need of further study. Linker histones are highly abundant nuclear proteins about which we know too little.

  18. Halo Substructure Towards the Galactic Center

    NASA Astrophysics Data System (ADS)

    Amy, Paul Martin; Martin, Charles; Newberg, Heidi Jo; Shelton, Siddartha; Carlin, Jeffrey L.; Willett, Benjamin A.

    2017-01-01

    We measure the velocity substructure of blue horizontal branch stars in Data Release 10 of the Sloan Digital Sky Survey, particularly in the regions of the Hermus Stream, the Hyllus Stream, and the Hercules-Aquila Cloud. These stars are concentrated at lower latitudes (b < 50°) in the first quadrant (0°substructure, and N-body simulations that plausibly replicate the morphologies of the observed tidal debris. From comparison with N-body simulations, we estimate the mass of the stream progenitors. This project was funded by a Rensselaer Presidential Fellowship, NSF grants AST 14-09421 and AST 16-15688, the NASA/NY Space Grant fellowship, and contributions made by The Marvin Clan, Babette Josephs, Manit Limlamai, and the 2015 Crowd Funding Campaign to Support Milky Way Research.

  19. Substructure coupling in the frequency domain

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Frequency domain analysis was found to be a suitable method for determining the transient response of systems subjected to a wide variety of loads. However, since a large number of calculations are performed within the discrete frequency loop, the method loses it computational efficiency if the loads must be represented by a large number of discrete frequencies. It was also discovered that substructure coupling in the frequency domain work particularly well for analyzing structural system with a small number of interface and loaded degrees of freedom. It was discovered that substructure coupling in the frequency domain can lead to an efficient method of obtaining natural frequencies of undamped structures. It was also found that the damped natural frequencies of a system may be determined using frequency domain techniques.

  20. Substructure Discovery of Macro-Operators

    DTIC Science & Technology

    1988-05-01

    Specifically, the PLAND (PLAN Discovery) system discovers macro-operators ( macrops ) of action subsequences by searching for interesting substructures in...construction in two important areas. Unlike [Andreae84] and [Minton85], PLAND discovers macrops from observation and does not use examples to learn the new...structures . The another difference is that PLAND does not use a problem solver to determine what the macrops for a task should be (as is done in

  1. Precision Jet Substructure from Boosted Event Shapes

    NASA Astrophysics Data System (ADS)

    Feige, Ilya; Schwartz, Matthew D.; Stewart, Iain W.; Thaler, Jesse

    2012-08-01

    Jet substructure has emerged as a critical tool for LHC searches, but studies so far have relied heavily on shower Monte Carlo simulations, which formally approximate QCD at the leading-log level. We demonstrate that systematic higher-order QCD computations of jet substructure can be carried out by boosting global event shapes by a large momentum Q and accounting for effects due to finite jet size, initial-state radiation (ISR), and the underlying event (UE) as 1/Q corrections. In particular, we compute the 2-subjettiness substructure distribution for boosted Z→qq¯ events at the LHC at next-to-next-to-next-to-leading-log order. The calculation is greatly simplified by recycling known results for the thrust distribution in e+e- collisions. The 2-subjettiness distribution quickly saturates, becoming Q independent for Q≳400GeV. Crucially, the effects of jet contamination from ISR/UE can be subtracted out analytically at large Q without knowing their detailed form. Amusingly, the Q=∞ and Q=0 distributions are related by a scaling by e up to next-to-leading-log order.

  2. Substructures in Simulations of Relativistic Jet Formation

    NASA Astrophysics Data System (ADS)

    Garcia, Raphael de Oliveira; Oliveira, Samuel Rocha de

    2017-04-01

    We present a set of simulations of relativistic jets from accretion disk initial setup with numerical solutions of a system of general-relativistic magnetohydrodynamics (GRMHD) partial differential equations in a fixed black hole (BH) spacetime which is able to show substructures formations inside the jet as well as lobe formation on the jet head. For this, we used a central scheme of finite volume method without dimensional split and with no Riemann solvers namely the Nessyahu-Tadmor method. Thus, we were able to obtain stable numerical solutions with spurious oscillations under control and with no excessive numerical dissipation. Therefore, we developed some setups for initial conditions capable of simulating the formation of relativistic jets from the accretion disk falling onto central black hole until its ejection, both immersed in a magnetosphere. In our simulations, we were able to observe some substructure of a jet created from an accretion initial disk, namely, jet head, knots, cocoon, and lobe. Also, we present an explanation for cocoon formation and lobe formation. Each initial scenario was determined by ratio between disk density and magnetosphere density, showing that this relation is very important for the shape of the jet and its substructures.

  3. Substructures in Simulations of Relativistic Jet Formation

    NASA Astrophysics Data System (ADS)

    Garcia, Raphael de Oliveira; Oliveira, Samuel Rocha de

    2017-02-01

    We present a set of simulations of relativistic jets from accretion disk initial setup with numerical solutions of a system of general-relativistic magnetohydrodynamics (GRMHD) partial differential equations in a fixed black hole (BH) spacetime which is able to show substructures formations inside the jet as well as lobe formation on the jet head. For this, we used a central scheme of finite volume method without dimensional split and with no Riemann solvers namely the Nessyahu-Tadmor method. Thus, we were able to obtain stable numerical solutions with spurious oscillations under control and with no excessive numerical dissipation. Therefore, we developed some setups for initial conditions capable of simulating the formation of relativistic jets from the accretion disk falling onto central black hole until its ejection, both immersed in a magnetosphere. In our simulations, we were able to observe some substructure of a jet created from an accretion initial disk, namely, jet head, knots, cocoon, and lobe. Also, we present an explanation for cocoon formation and lobe formation. Each initial scenario was determined by ratio between disk density and magnetosphere density, showing that this relation is very important for the shape of the jet and its substructures.

  4. Design sensitivity analysis of boundary element substructures

    NASA Technical Reports Server (NTRS)

    Kane, James H.; Saigal, Sunil; Gallagher, Richard H.

    1989-01-01

    The ability to reduce or condense a three-dimensional model exactly, and then iterate on this reduced size model representing the parts of the design that are allowed to change in an optimization loop is discussed. The discussion presents the results obtained from an ongoing research effort to exploit the concept of substructuring within the structural shape optimization context using a Boundary Element Analysis (BEA) formulation. The first part contains a formulation for the exact condensation of portions of the overall boundary element model designated as substructures. The use of reduced boundary element models in shape optimization requires that structural sensitivity analysis can be performed. A reduced sensitivity analysis formulation is then presented that allows for the calculation of structural response sensitivities of both the substructured (reduced) and unsubstructured parts of the model. It is shown that this approach produces significant computational economy in the design sensitivity analysis and reanalysis process by facilitating the block triangular factorization and forward reduction and backward substitution of smaller matrices. The implementatior of this formulation is discussed and timings and accuracies of representative test cases presented.

  5. Identifying a new particle with jet substructures

    NASA Astrophysics Data System (ADS)

    Han, Chengcheng; Kim, Doojin; Kim, Minho; Kong, Kyoungchul; Lim, Sung Hak; Park, Myeonghun

    2017-01-01

    We investigate a potential of determining properties of a new heavy resonance of mass O(1) TeV which decays to collimated jets via heavy Standard Model intermediary states, exploiting jet substructure techniques. Employing the Z gauge boson as a concrete example for the intermediary state, we utilize a "merged jet" defined by a large jet size to capture the two quarks from its decay. The use of the merged jet benefits the identification of a Z-induced jet as a single, reconstructed object without any combinatorial ambiguity. We find that jet substructure procedures may enhance features in some kinematic observables formed with subjet four-momenta extracted from a merged jet. This observation motivates us to feed subjet momenta into the matrix elements associated with plausible hypotheses on the nature of the heavy resonance, which are further processed to construct a matrix element method (MEM)-based observable. For both moderately and highly boosted Z bosons, we demonstrate that the MEM in combination with jet substructure techniques can be a very powerful tool for identifying its physical properties. We also discuss effects from choosing different jet sizes for merged jets and jet-grooming parameters upon the MEM analyses.

  6. Composite Octet Searches with Jet Substructure

    SciTech Connect

    Bai, Yang; Shelton, Jessie; /Yale U.

    2012-02-14

    Many new physics models with strongly interacting sectors predict a mass hierarchy between the lightest vector meson and the lightest pseudoscalar mesons. We examine the power of jet substructure tools to extend the 7 TeV LHC sensitivity to these new states for the case of QCD octet mesons, considering both two gluon and two b-jet decay modes for the pseudoscalar mesons. We develop both a simple dijet search using only the jet mass and a more sophisticated jet substructure analysis, both of which can discover the composite octets in a dijet-like signature. The reach depends on the mass hierarchy between the vector and pseudoscalar mesons. We find that for the pseudoscalar-to-vector meson mass ratio below approximately 0.2 the simple jet mass analysis provides the best discovery limit; for a ratio between 0.2 and the QCD-like value of 0.3, the sophisticated jet substructure analysis has the best discovery potential; for a ratio above approximately 0.3, the standard four-jet analysis is more suitable.

  7. Star formation and substructure in galaxy clusters

    SciTech Connect

    Cohen, Seth A.; Hickox, Ryan C.; Wegner, Gary A.; Einasto, Maret; Vennik, Jaan

    2014-03-10

    We investigate the relationship between star formation (SF) and substructure in a sample of 107 nearby galaxy clusters using data from the Sloan Digital Sky Survey. Several past studies of individual galaxy clusters have suggested that cluster mergers enhance cluster SF, while others find no such relationship. The SF fraction in multi-component clusters (0.228 ± 0.007) is higher than that in single-component clusters (0.175 ± 0.016) for galaxies with M{sub r}{sup 0.1}<−20.5. In both single- and multi-component clusters, the fraction of star-forming galaxies increases with clustercentric distance and decreases with local galaxy number density, and multi-component clusters show a higher SF fraction than single-component clusters at almost all clustercentric distances and local densities. Comparing the SF fraction in individual clusters to several statistical measures of substructure, we find weak, but in most cases significant at greater than 2σ, correlations between substructure and SF fraction. These results could indicate that cluster mergers may cause weak but significant SF enhancement in clusters, or unrelaxed clusters exhibit slightly stronger SF due to their less evolved states relative to relaxed clusters.

  8. Consultant/Linker Knowledge and Skills Inventory.

    ERIC Educational Resources Information Center

    Smink, Jay

    The Consultant/Linker Knowledge and Skills Inventory is used to assess both existing and needed levels of knowledge and skills for consulting with school staff. The inventory is self-administered, and requires 20 to 30 minutes to complete. For each item, knowledge and skill are rated low, medium, or high; and need for improvement is rated none,…

  9. Transient inter-cellular polymeric linker.

    PubMed

    Ong, Siew-Min; He, Lijuan; Thuy Linh, Nguyen Thi; Tee, Yee-Han; Arooz, Talha; Tang, Guping; Tan, Choon-Hong; Yu, Hanry

    2007-09-01

    Three-dimensional (3D) tissue-engineered constructs with bio-mimicry cell-cell and cell-matrix interactions are useful in regenerative medicine. In cell-dense and matrix-poor tissues of the internal organs, cells support one another via cell-cell interactions, supplemented by small amount of the extra-cellular matrices (ECM) secreted by the cells. Here we connect HepG2 cells directly but transiently with inter-cellular polymeric linker to facilitate cell-cell interaction and aggregation. The linker consists of a non-toxic low molecular-weight polyethyleneimine (PEI) backbone conjugated with multiple hydrazide groups that can aggregate cells within 30 min by reacting with the aldehyde handles on the chemically modified cell-surface glycoproteins. The cells in the cellular aggregates proliferated; and maintained the cortical actin distribution of the 3D cell morphology while non-aggregated cells died over 7 days of suspension culture. The aggregates lost distinguishable cell-cell boundaries within 3 days; and the ECM fibers became visible around cells from day 3 onwards while the inter-cellular polymeric linker disappeared from the cell surfaces over time. The transient inter-cellular polymeric linker can be useful for forming 3D cellular and tissue constructs without bulk biomaterials or extensive network of engineered ECM for various applications.

  10. Modeling neck linker of kinesin motor movement with MRSR stochastic differential equation

    NASA Astrophysics Data System (ADS)

    Razali, Wan Qashishah Akmal Wan; Ramli, Siti Norafidah Mohd; Radiman, Shahidan

    2016-11-01

    Stochastic differential equation has a significant role in a range of biological areas including molecular motor like kinesin motor. Mean-reverting square root (MRSR) stochastic differential equation is commonly used in economics and finance areas. In this study, we use the MRSR stochastic differential equation to model neck linker motion of kinesin motor by considering the possibilities of rightward direction and occasionally in the leftward direction of kinesin movements. This neck linker docking model of kinesin motor incorporates the conformational change in the chemical kinetics and the tethered diffusion of the free head of kinesin motor. Here, we demonstrate this model by using Hookean spring method which referred to the stiffness model of neck linker. The motion of kinesin motor seems to be well described to move in unidirectional way with volatile behavior based on MRSR rather than common stochastic differential equation [DOI 10.1007/s11538-011-9697-6].

  11. 5. DOWNSTREAM ELEVATION OF BRIDGE AND SUBSTRUCTURE (with graduated meter ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. DOWNSTREAM ELEVATION OF BRIDGE AND SUBSTRUCTURE (with graduated meter pole); VIEW TO NORTH-NORTHEAST. - Auwaiakeakua Bridge, Spanning Auwaiakekua Gulch at Mamalahoa Highway, Waikoloa, Hawaii County, HI

  12. Substructurability: the effect of interface location on a real-time dynamic substructuring test

    PubMed Central

    Neild, S. A.; Lowenberg, M.; Szalai, R.; Krauskopf, B.

    2016-01-01

    A full-scale experimental test for large and complex structures is not always achievable. This can be due to many reasons, the most prominent one being the size limitations of the test. Real-time dynamic substructuring is a hybrid testing method where part of the system is modelled numerically and the rest of the system is kept as the physical test specimen. The numerical–physical parts are connected via actuators and sensors and the interface is controlled by advanced algorithms to ensure that the tested structure replicates the emulated system with sufficient accuracy. The main challenge in such a test is to overcome the dynamic effects of the actuator and associated controller, that inevitably introduce delay into the substructured system which, in turn, can destabilize the experiment. To date, most research concentrates on developing control strategies for stable recreation of the full system when the interface location is given a priori. Therefore, substructurability is mostly studied in terms of control. Here, we consider the interface location as a parameter and study its effect on the stability of the system in the presence of delay due to actuator dynamics and define substructurability as the system’s tolerance to delay in terms of the different interface locations. It is shown that the interface location has a major effect on the tolerable delays in an experiment and, therefore, careful selection of it is necessary. PMID:27616930

  13. Substructurability: the effect of interface location on a real-time dynamic substructuring test.

    PubMed

    Terkovics, N; Neild, S A; Lowenberg, M; Szalai, R; Krauskopf, B

    2016-08-01

    A full-scale experimental test for large and complex structures is not always achievable. This can be due to many reasons, the most prominent one being the size limitations of the test. Real-time dynamic substructuring is a hybrid testing method where part of the system is modelled numerically and the rest of the system is kept as the physical test specimen. The numerical-physical parts are connected via actuators and sensors and the interface is controlled by advanced algorithms to ensure that the tested structure replicates the emulated system with sufficient accuracy. The main challenge in such a test is to overcome the dynamic effects of the actuator and associated controller, that inevitably introduce delay into the substructured system which, in turn, can destabilize the experiment. To date, most research concentrates on developing control strategies for stable recreation of the full system when the interface location is given a priori. Therefore, substructurability is mostly studied in terms of control. Here, we consider the interface location as a parameter and study its effect on the stability of the system in the presence of delay due to actuator dynamics and define substructurability as the system's tolerance to delay in terms of the different interface locations. It is shown that the interface location has a major effect on the tolerable delays in an experiment and, therefore, careful selection of it is necessary.

  14. Disruption of the IS6-AID Linker Affects Voltage-gated Calcium Channel Inactivation and Facilitation

    PubMed Central

    Findeisen, Felix

    2009-01-01

    Two processes dominate voltage-gated calcium channel (CaV) inactivation: voltage-dependent inactivation (VDI) and calcium-dependent inactivation (CDI). The CaVβ/CaVα1-I-II loop and Ca2+/calmodulin (CaM)/CaVα1–C-terminal tail complexes have been shown to modulate each, respectively. Nevertheless, how each complex couples to the pore and whether each affects inactivation independently have remained unresolved. Here, we demonstrate that the IS6–α-interaction domain (AID) linker provides a rigid connection between the pore and CaVβ/I-II loop complex by showing that IS6-AID linker polyglycine mutations accelerate CaV1.2 (L-type) and CaV2.1 (P/Q-type) VDI. Remarkably, mutations that either break the rigid IS6-AID linker connection or disrupt CaVβ/I-II association sharply decelerate CDI and reduce a second Ca2+/CaM/CaVα1–C-terminal–mediated process known as calcium-dependent facilitation. Collectively, the data strongly suggest that components traditionally associated solely with VDI, CaVβ and the IS6-AID linker, are essential for calcium-dependent modulation, and that both CaVβ-dependent and CaM-dependent components couple to the pore by a common mechanism requiring CaVβ and an intact IS6-AID linker. PMID:19237593

  15. Substructure of fuzzy dark matter haloes

    NASA Astrophysics Data System (ADS)

    Du, Xiaolong; Behrens, Christoph; Niemeyer, Jens C.

    2017-02-01

    We derive the halo mass function (HMF) for fuzzy dark matter (FDM) by solving the excursion set problem explicitly with a mass-dependent barrier function, which has not been done before. We find that compared to the naive approach of the Sheth-Tormen HMF for FDM, our approach has a higher cutoff mass and the cutoff mass changes less strongly with redshifts. Using merger trees constructed with a modified version of the Lacey & Cole formalism that accounts for suppressed small-scale power and the scale-dependent growth of FDM haloes and the semi-analytic GALACTICUS code, we study the statistics of halo substructure including the effects from dynamical friction and tidal stripping. We find that if the dark matter is a mixture of cold dark matter (CDM) and FDM, there will be a suppression on the halo substructure on small scales which may be able to solve the missing satellites problem faced by the pure CDM model. The suppression becomes stronger with increasing FDM fraction or decreasing FDM mass. Thus, it may be used to constrain the FDM model.

  16. Early dynamical evolution of young substructured clusters

    NASA Astrophysics Data System (ADS)

    Dorval, Julien; Boily, Christian

    2017-03-01

    Stellar clusters form with a high level of substructure, inherited from the molecular cloud and the star formation process. Evidence from observations and simulations also indicate the stars in such young clusters form a subvirial system. The subsequent dynamical evolution can cause important mass loss, ejecting a large part of the birth population in the field. It can also imprint the stellar population and still be inferred from observations of evolved clusters. Nbody simulations allow a better understanding of these early twists and turns, given realistic initial conditions. Nowadays, substructured, clumpy young clusters are usually obtained through pseudo-fractal growth and velocity inheritance. We introduce a new way to create clumpy initial conditions through a ''Hubble expansion'' which naturally produces self consistent clumps, velocity-wise. In depth analysis of the resulting clumps shows consistency with hydrodynamical simulations of young star clusters. We use these initial conditions to investigate the dynamical evolution of young subvirial clusters. We find the collapse to be soft, with hierarchical merging leading to a high level of mass segregation. The subsequent evolution is less pronounced than the equilibrium achieved from a cold collapse formation scenario.

  17. Spectroscopic study of the light-harvesting protein C-phycocyanin associated with colorless linker peptides

    SciTech Connect

    Pizarro, Shelly Ann

    2000-05-01

    The phycobilisome (PBS) light-harvesting antenna is composed of chromophore-containing biliproteins and 'colorless' linker peptides and is structurally designed to support unidirectional transfer of excitation energy from the periphery of the PBS to its core. The linker peptides have a unique role in this transfer process by modulating the spectral properties of the associated biliprotein. There is only one three-dimensional structure of a biliprotein/linker complex available to date (APC/LC7.8) and the mechanism of interaction between these two proteins remains unknown. This study brings together a detailed spectroscopic characterization of C-Phycocyanin (PC)-linker complexes (isolated from Synechococcus sp. PCC 7002) with proteomic analysis of the linker amino acid sequences to produce a model for biliprotein/linker interaction. The amino acid sequences of the rod linkers [LR8.9, LR32.3 and LRC28.5] were examined to identify evolutionarily conserved regions important to either the structure or function of this protein family. Although there is not one common homologous site among all the linkers, there are strong trends across each separate subset (LC, LR and LRC) and the N-terminal segments of both LR32.3 and LRC28.5 display multiple regions of similarity with other linkers. Predictions of the secondary structure of LR32.3 and LRC28.5, and comparison to the crystal structure of LC7.8, further narrowed the candidates for interaction sites with the PC chromophores. Measurements of the absorption, fluorescence, CD and excitation anisotropy of PC trimer, PC/LR32.3, and PC/LRC28.5, document the spectroscopic effect of each linker peptide on the PC chromophores at a series of temperatures (298 to 77 K). Because L

  18. Characterization of T-Even Bacteriophage Substructures

    PubMed Central

    Cummings, Donald J.; Kusy, A. R.; Chapman, V. A.; DeLong, S. S.; Stone, K. R.

    1970-01-01

    T-even bacteriophages were grown and purified in bulk quantities. The protein coats were disrupted into their component substructures by treatment with 67% dimethyl sulfoxide (DMSO). Tail fibers and tubes were purified on glycerol-CsCl-D2O gradients and examined with respect to sedimentation properties, subunit molecular weights, amino acid composition, isoelectric points, and morphology. It was found that intact tail fibers had a sedimentation coefficient of 12 to 13S and that dissociated fibers consisted of three classes of proteins having molecular weights of 150 K ± 10, 42 K ± 4, and 28 K ± 3 daltons. A model was constructed in which the 150-K subunit folded back on itself twice to give a three-stranded rope. Each 150-K subunit then represented a half-fiber and it was proposed that the role of the 42- and 28-K subunits was to hold each half-fiber together as well as serve as a possible link with other substructures. Isoelectric point studies also indicated that there were three different proteins with pI values of 3.5, 5.7, and 8.0. Amino acid analyses indicated that fibers had a composition distinct from other phage substructures. In addition, a striking difference was noted in the content of tryptophan among the phages examined. T4B had three to five times more tryptophan than did T2L, T2H, T4D, and T6. Intact tail tubes had an S20,w of 31 to 38S and dissociated tubes consisted of three proteins of molecular weights 57 K ± 5, 38 K ± 4, and 25 K ± 3 daltons. Based on degradation studies with DMSO, it was proposed that these three proteins were arranged in a helical array yielding the tube structure. Isoelectric point studies indicated that there were three major proteins in the tube whose pI values were 5.1, 5.7, and 8.5. No significant differences were observed in the amino acid content of tubes obtained from all the T-even bacteriophages. Images PMID:5497900

  19. Exploring dark matter with Milky Way substructure.

    PubMed

    Kuhlen, Michael; Madau, Piero; Silk, Joseph

    2009-08-21

    The unambiguous detection of dark matter annihilation in our Galaxy would unravel one of the most outstanding puzzles in particle physics and cosmology. Recent observations have motivated models in which the annihilation rate is boosted by the Sommerfeld effect, a nonperturbative enhancement arising from a long-range attractive force. We applied the Sommerfeld correction to Via Lactea II, a high-resolution N-body simulation of a Milky Way-sized galaxy, to investigate the phase-space structure of the galactic halo. We found that the annihilation luminosity from kinematically cold substructure could be enhanced by orders of magnitude relative to previous calculations, leading to the prediction of gamma-ray fluxes from as many as several hundred dark clumps that should be detectable by the Fermi satellite.

  20. A case of poor substructure diagnostics

    NASA Technical Reports Server (NTRS)

    Butler, Thomas G.

    1992-01-01

    The NASTRAN Manuals in the substructuring area are all geared toward instant success, but the solution paths are fraught with many traps for human error. Thus, the probability of suffering a fatal abort is high. In such circumstances, the necessity for diagnostics that are user friendly is paramount. This paper is written in the spirit of improving the diagnostics as well as the documentation in one area where the author felt he was backed into a blind corner as a result of his having committed a data oversight. This topic is aired by referring to an analysis of a particular structure. The structure, under discussion, used a number of local coordinate systems that simplified the preparation of input data. The principle features of this problem are introduced by reference to a series of figures.

  1. Early dynamical evolution of substructured stellar clusters

    NASA Astrophysics Data System (ADS)

    Dorval, Julien; Boily, Christian

    2015-08-01

    It is now widely accepted that stellar clusters form with a high level of substructure (Kuhn et al. 2014, Bate 2009), inherited from the molecular cloud and the star formation process. Evidence from observations and simulations also indicate the stars in such young clusters form a subvirial system (Kirk et al. 2007, Maschberger et al. 2010). The subsequent dynamical evolution can cause important mass loss, ejecting a large part of the birth population in the field. It can also imprint the stellar population and still be inferred from observations of evolved clusters. Nbody simulations allow a better understanding of these early twists and turns, given realistic initial conditions. Nowadays, substructured, clumpy young clusters are usually obtained through pseudo-fractal growth (Goodwin et al. 2004) and velocity inheritance. Such models are visually realistics and are very useful, they are however somewhat artificial in their velocity distribution. I introduce a new way to create clumpy initial conditions through a "Hubble expansion" which naturally produces self consistent clumps, velocity-wise. A velocity distribution analysis shows the new method produces realistic models, consistent with the dynamical state of the newly created cores in hydrodynamic simulation of cluster formation (Klessen & Burkert 2000). I use these initial conditions to investigate the dynamical evolution of young subvirial clusters, up to 80000 stars. I find an overall soft evolution, with hierarchical merging leading to a high level of mass segregation. I investigate the influence of the mass function on the fate of the cluster, specifically on the amount of mass loss induced by the early violent relaxation. Using a new binary detection algorithm, I also find a strong processing of the native binary population.

  2. Two novel phycoerythrin-associated linker proteins in the marine cyanobacterium Synechococcus sp. strain WH8102.

    PubMed

    Six, Christophe; Thomas, Jean-Claude; Thion, Laurent; Lemoine, Yves; Zal, Frank; Partensky, Frédéric

    2005-03-01

    The recent availability of the whole genome of Synechococcus sp. strain WH8102 allows us to have a global view of the complex structure of the phycobilisomes of this marine picocyanobacterium. Genomic analyses revealed several new characteristics of these phycobilisomes, consisting of an allophycocyanin core and rods made of one type of phycocyanin and two types of phycoerythrins (I and II). Although the allophycocyanin appears to be similar to that found commonly in freshwater cyanobacteria, the phycocyanin is simpler since it possesses only one complete set of alpha and beta subunits and two rod-core linkers (CpcG1 and CpcG2). It is therefore probably made of a single hexameric disk per rod. In contrast, we have found two novel putative phycoerythrin-associated linker polypeptides that appear to be specific for marine Synechococcus spp. The first one (SYNW2000) is unusually long (548 residues) and apparently results from the fusion of a paralog of MpeC, a phycoerythrin II linker, and of CpeD, a phycoerythrin-I linker. The second one (SYNW1989) has a more classical size (300 residues) and is also an MpeC paralog. A biochemical analysis revealed that, like MpeC, these two novel linkers were both chromophorylated with phycourobilin. Our data suggest that they are both associated (partly or totally) with phycoerythrin II, and we propose to name SYNW2000 and SYNW1989 MpeD and MpeE, respectively. We further show that acclimation of phycobilisomes to high light leads to a dramatic reduction of MpeC, whereas the two novel linkers are not significantly affected. Models for the organization of the rods are proposed.

  3. Two Novel Phycoerythrin-Associated Linker Proteins in the Marine Cyanobacterium Synechococcus sp. Strain WH8102

    PubMed Central

    Six, Christophe; Thomas, Jean-Claude; Thion, Laurent; Lemoine, Yves; Zal, Frank; Partensky, Frédéric

    2005-01-01

    The recent availability of the whole genome of Synechococcus sp. strain WH8102 allows us to have a global view of the complex structure of the phycobilisomes of this marine picocyanobacterium. Genomic analyses revealed several new characteristics of these phycobilisomes, consisting of an allophycocyanin core and rods made of one type of phycocyanin and two types of phycoerythrins (I and II). Although the allophycocyanin appears to be similar to that found commonly in freshwater cyanobacteria, the phycocyanin is simpler since it possesses only one complete set of α and β subunits and two rod-core linkers (CpcG1 and CpcG2). It is therefore probably made of a single hexameric disk per rod. In contrast, we have found two novel putative phycoerythrin-associated linker polypeptides that appear to be specific for marine Synechococcus spp. The first one (SYNW2000) is unusually long (548 residues) and apparently results from the fusion of a paralog of MpeC, a phycoerythrin II linker, and of CpeD, a phycoerythrin-I linker. The second one (SYNW1989) has a more classical size (300 residues) and is also an MpeC paralog. A biochemical analysis revealed that, like MpeC, these two novel linkers were both chromophorylated with phycourobilin. Our data suggest that they are both associated (partly or totally) with phycoerythrin II, and we propose to name SYNW2000 and SYNW1989 MpeD and MpeE, respectively. We further show that acclimation of phycobilisomes to high light leads to a dramatic reduction of MpeC, whereas the two novel linkers are not significantly affected. Models for the organization of the rods are proposed. PMID:15716439

  4. Linker dependence of interfacial electron transfer rates in Fe(II)-polypyridine sensitized solar cells

    NASA Astrophysics Data System (ADS)

    Bowman, David N.; Mukherjee, Sriparna; Barnes, Lyndsay J.; Jakubikova, Elena

    2015-04-01

    Dye-sensitized solar cells (DSSCs) convert solar energy to electricity employing dye molecules attached to a semiconductor surface. Some of the most efficient DSSCs use Ru-based chromophores. Fe-based dyes represent a cheaper and more environmentally friendly alternative to these expensive and toxic dyes. The photoactive state of Fe-based chromophores responsible for charge-separation at the dye-semiconductor interface is, however, deactivated on a sub-picosecond time scale via the intersystem crossing (ISC) into a manifold of low-lying photo-inactive quintet states. Therefore, development of Fe-based dyes capable of fast interfacial electron transfer (IET) leading to efficient charge separation on a time scale competitive with the ISC events is important. This work investigates how linker groups anchoring a prototypical Fe-based dye [Fe(bpy-L)2(CN)2] (bpy = 2,2‧-bipyridine, L = linker group) onto the TiO2 semiconductor surface influence the IET rates in the dye-semiconductor assemblies. Linker groups investigated include carboxylic acid, phosphonic acid, hydroxamate, catechol, and acetylacetonate. We employ time-dependent density functional theory (TD-DFT) to obtain absorption spectra of [Fe(bpy-L)2(CN)2] with each linker, and quantum dynamics simulations to investigate the IET rates between the dye and the (101) TiO2 anatase surface. For all attachments, TD-DFT calculations show similar absorption spectra with two main bands corresponding to the metal-to-ligand charge transfer transitions. The quantum dynamics simulations predict that the utilization of the hydroxamate linker instead of the commonly used carboxylic acid linker will lead to a more efficient IET and better photon-to-current conversion efficiencies in Fe(II)-polypyridine sensitized solar cells.

  5. Desmosine-Inspired Cross-Linkers for Hyaluronan Hydrogels

    NASA Astrophysics Data System (ADS)

    Hagel, Valentin; Mateescu, Markus; Southan, Alexander; Wegner, Seraphine V.; Nuss, Isabell; Haraszti, Tamás; Kleinhans, Claudia; Schuh, Christian; Spatz, Joachim P.; Kluger, Petra J.; Bach, Monika; Tussetschläger, Stefan; Tovar, Günter E. M.; Laschat, Sabine; Boehm, Heike

    2013-06-01

    We designed bioinspired cross-linkers based on desmosine, the cross-linker in natural elastin, to prepare hydrogels with thiolated hyaluronic acid. These short, rigid cross-linkers are based on pyridinium salts (as in desmosine) and can connect two polymer backbones. Generally, the obtained semi-synthetic hydrogels are form-stable, can withstand repeated stress, have a large linear-elastic range, and show strain stiffening behavior typical for biopolymer networks. In addition, it is possible to introduce a positive charge to the core of the cross-linker without affecting the gelation efficiency, or consequently the network connectivity. However, the mechanical properties strongly depend on the charge of the cross-linker. The properties of the presented hydrogels can thus be tuned in a range important for engineering of soft tissues by controlling the cross-linking density and the charge of the cross-linker.

  6. The Sam68 nuclear body is composed of two RNase-sensitive substructures joined by the adaptor HNRNPL

    PubMed Central

    Yamashita, Seisuke; Goshima, Naoki

    2016-01-01

    The mammalian cell nucleus contains membraneless suborganelles referred to as nuclear bodies (NBs). Some NBs are formed with an architectural RNA (arcRNA) as the structural core. Here, we searched for new NBs that are built on unidentified arcRNAs by screening for ribonuclease (RNase)-sensitive NBs using 32,651 fluorescently tagged human cDNA clones. We identified 32 tagged proteins that required RNA for their localization in distinct nuclear foci. Among them, seven RNA-binding proteins commonly localized in the Sam68 nuclear body (SNB), which was disrupted by RNase treatment. Knockdown of each SNB protein revealed that SNBs are composed of two distinct RNase-sensitive substructures. One substructure is present as a distinct NB, termed the DBC1 body, in certain conditions, and the more dynamic substructure including Sam68 joins to form the intact SNB. HNRNPL acts as the adaptor to combine the two substructures and form the intact SNB through the interaction of two sets of RNA recognition motifs with the putative arcRNAs in the respective substructures. PMID:27377249

  7. Flexible substructure online hybrid test system using conventional testing devices

    NASA Astrophysics Data System (ADS)

    Wang, Tao; Nakashima, Masayoshi

    2013-09-01

    This paper presents a substructure online hybrid test system that is extensible for geographically distributed tests. This system consists of a set of devices conventionally used for cyclic tests to load the tested substructures onto the target displacement or the target force. Due to their robustness and portability, individual sets of conventional loading devices can be transported and reconfigured to realize physical loading in geographically remote laboratories. Another appealing feature is the flexible displacement-force mixed control that is particularly suitable for specimens having large disparities in stiffness during various performance stages. To conduct a substructure online hybrid test, an extensible framework is developed, which is equipped with a generalized interface to encapsulate each substructure. Multiple tested substructures and analyzed substructures using various structural program codes can be accommodated within the single framework, simply interfaced with the boundary displacements and forces. A coordinator program is developed to keep the boundaries among all substructures compatible and equilibrated. An Internet-based data exchange scheme is also devised to transfer data among computers equipped with different software environments. A series of online hybrid tests are introduced, and the portability, flexibility, and extensibility of the online hybrid test system are demonstrated.

  8. The Smad3 linker region contains a transcriptional activation domain.

    PubMed

    Wang, Guannan; Long, Jianyin; Matsuura, Isao; He, Dongming; Liu, Fang

    2005-02-15

    Transforming growth factor-beta (TGF-beta)/Smads regulate a wide variety of biological responses through transcriptional regulation of target genes. Smad3 plays a key role in TGF-beta/Smad-mediated transcriptional responses. Here, we show that the proline-rich linker region of Smad3 contains a transcriptional activation domain. When the linker region is fused to a heterologous DNA-binding domain, it activates transcription. We show that the linker region physically interacts with p300. The adenovirus E1a protein, which binds to p300, inhibits the transcriptional activity of the linker region, and overexpression of p300 can rescue the linker-mediated transcriptional activation. In contrast, an adenovirus E1a mutant, which cannot bind to p300, does not inhibit the linker-mediated transcription. The native Smad3 protein lacking the linker region is unable to mediate TGF-beta transcriptional activation responses, although it can be phosphorylated by the TGF-beta receptor at the C-terminal tail and has a significantly increased ability to form a heteromeric complex with Smad4. We show further that the linker region and the C-terminal domain of Smad3 synergize for transcriptional activation in the presence of TGF-beta. Thus our findings uncover an important function of the Smad3 linker region in Smad-mediated transcriptional control.

  9. Synthesised H ∞ / μ Control Design for Dynamically Substructured Systems

    NASA Astrophysics Data System (ADS)

    Yamaguchi, T.; Stoten, D. P.

    2016-09-01

    In the dynamically substructured system (DSS) testing technique, a controller that synchronises the responses of physical and numerical substructures is an essential part of the testing scheme to ensure synchronisation fidelity. This paper discusses a novel approach that generates a two-degree-of-freedom (2-DOF) output feedback controller for multi-input, multioutput (MIMO) DSS via control synthesis. This 2-DOF output feedback controller yields robust stability and robust performance of the physical/numerical substructure synchronisation and enables controller tuning in the frequency domain. Simulation and experimental results have been shown to validate the efficacy of the method.

  10. Substructuring by Lagrange multipliers for solids and plates

    SciTech Connect

    Mandel, J.; Tezaur, R.; Farhat, C.

    1996-12-31

    We present principles and theoreretical foundation of a substructuring method for large structural problems. The algorithm is preconditioned conjugate gradients on a subspace for the dual problem. The preconditioning is proved asymptotically optimal and the method is shown to be parallel scalable, i.e., the condition number is bounded independently of the number of substructures. For plate problems, a special modification is needed that retains continuity of the displacement solution at substructure crosspoints, resulting in an asymptically optimal method. The results are confirmed by numerical experiments.

  11. Substructure System Identification for Finite Element Model Updating

    NASA Technical Reports Server (NTRS)

    Craig, Roy R., Jr.; Blades, Eric L.

    1997-01-01

    This report summarizes research conducted under a NASA grant on the topic 'Substructure System Identification for Finite Element Model Updating.' The research concerns ongoing development of the Substructure System Identification Algorithm (SSID Algorithm), a system identification algorithm that can be used to obtain mathematical models of substructures, like Space Shuttle payloads. In the present study, particular attention was given to the following topics: making the algorithm robust to noisy test data, extending the algorithm to accept experimental FRF data that covers a broad frequency bandwidth, and developing a test analytical model (TAM) for use in relating test data to reduced-order finite element models.

  12. Effects of the linker region on the structure and function of modular GH5 cellulases

    PubMed Central

    Ruiz, Diego M.; Turowski, Valeria R.; Murakami, Mario T.

    2016-01-01

    The association of glycosyl hydrolases with catalytically inactive modules is a successful evolutionary strategy that is commonly used by biomass-degrading microorganisms to digest plant cell walls. The presence of accessory domains in these enzymes is associated with properties such as higher catalytic efficiency, extension of the catalytic interface and targeting of the enzyme to the proper substrate. However, the importance of the linker region in the synergistic action of the catalytic and accessory domains remains poorly understood. Thus, this study examined how the inter-domain region affects the structure and function of modular GH5 endoglucanases, by using cellulase 5A from Bacillus subtilis (BsCel5A) as a model. BsCel5A variants featuring linkers with different stiffnesses or sizes were designed and extensively characterized, revealing that changes in flexibility or rigidity in this region differentially affect kinetic behavior. Regarding the linker length, we found that precise inter-domain spacing is required to enable efficient hydrolysis because excessively long or short linkers were equally detrimental to catalysis. Together, these findings identify molecular and structural features that may contribute to the rational design of chimeric and multimodular glycosyl hydrolases. PMID:27334041

  13. Detail view of Fanno Creek trestle, showing trestle substructure, view ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail view of Fanno Creek trestle, showing trestle substructure, view looking north - Oregon Electric Railroad, Fanno Creek Trestle, Garden Home to Wilsonville Segment, Milepost 34.7, Garden Home, Washington County, OR

  14. Dynamically Substructured System Testing for Railway Vehicle Pantographs

    NASA Astrophysics Data System (ADS)

    Stoten, D. P.; Yamaguchi, T.; Yamashita, Y.

    2016-09-01

    ]The overall objective of this paper is to establish a dynamically substructured system (DSS) testing approach for railway vehicle pantographs. In this approach a pilot study quasi-pantograph (QP) is tested within a laboratory environment, where the catenary wire, contact wire and catenary support (abbreviated as ‘catenary’ in this paper) are modelled as a numerical substructure. This is simulated in real time and in parallel with the operation of the physical substructure, i.e. the QP rig itself. The entire DSS is driven by parametric excitation within the catenary model, whilst the numerical and physical substructures are synchronised at their interface via the DSS control technique of [1]. Simulation and physical experimental investigations of the pilot QP rig, constructed within the Advanced Control and Test Laboratory at the University of Bristol, UK, demonstrate the efficacy of the method when subjected to parametric variations, unknown parameter values and parametric excitation.

  15. 10. DETAIL OF BRIDGE SUBSTRUCTURE, SHOWING ORIGINAL CONNECTION WITH IRON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. DETAIL OF BRIDGE SUBSTRUCTURE, SHOWING ORIGINAL CONNECTION WITH IRON PINS. VIEW LOOKING WEST FROM FACE OF EAST ABUTMENT. - Annisquam Bridge, Spanning Lobster Cove between Washington & River Streets, Gloucester, Essex County, MA

  16. Detail view of substructure, view looking at the south abutments ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail view of substructure, view looking at the south abutments and the pedestrian promenade - Spring Creek Bridge, Spanning Spring Creek at Milepoint 253.98 on Oregon to California Highway (US Route 97), Chiloquin, Klamath County, OR

  17. 65. VIEW LOOKING UPSTREAM FROM FLUME SUBSTRUCTURE, SHOWING COLUMBIA IMPROVEMENT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    65. VIEW LOOKING UPSTREAM FROM FLUME SUBSTRUCTURE, SHOWING COLUMBIA IMPROVEMENT COMPANY'S NEISSON CREEK SAWMILL. Print No. 177, November 1903 - Electron Hydroelectric Project, Along Puyallup River, Electron, Pierce County, WA

  18. 98. DETAIL VIEW OF STORM DAMAGE AND EXPOSED SUBSTRUCTURE, NORTHWEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    98. DETAIL VIEW OF STORM DAMAGE AND EXPOSED SUBSTRUCTURE, NORTHWEST SIDE OF 4TH TEE, LOOKING WEST - Huntington Beach Municipal Pier, Pacific Coast Highway at Main Street, Huntington Beach, Orange County, CA

  19. Is there substructure around M87?

    NASA Astrophysics Data System (ADS)

    Oldham, L. J.; Evans, N. W.

    2016-10-01

    We present a general method to identify infalling substructure in discrete data sets with position and line-of-sight velocity data. We exploit the fact that galaxies falling on to a brightest cluster galaxy (BCG) in a virialized cluster, or dwarf satellites falling on to a central galaxy like the Milky Way, follow nearly radial orbits. If the orbits are exactly radial, we show how to find the probability distribution for a satellite's energy, given a tracer density for the satellite population, by solving an Abel integral equation. This is an extension of Eddington's classical formula for the isotropic distribution function. When applied to a system of galaxies, clustering in energy space can then be quantified using the Kullback-Leibler divergence, and groups of objects can be identified which, though separated in the sky, may be falling in on the same orbit. This method is tested using mock data and applied to the satellite galaxy population around M87, the BCG in Virgo, and a number of associations that are found, which may represent infalling galaxy groups.

  20. Dislocation substructure in fatigued duplex stainless steel

    SciTech Connect

    Polak, J. . Lab. de Mecanique de Lille Inst. of Physical Metallurgy, Brno . Academy of Sciences); Degallaix, S. . Lab. de Mecanique de Lille); Kruml, T. . Academy of Sciences)

    1993-12-15

    Cyclic plastic straining of crystalline materials results in the formation of specific dislocation structures. Considerable progress in mapping and understanding internal dislocation structures has been achieved by studying single crystal behavior: however, most structural materials have a polycrystalline structure and investigations of polycrystals in comparison to single crystal behavior of simple metals prove to be very useful in understanding more complex materials. There are some classes of materials, however, with complicated structure which do not have a direct equivalent in single crystalline form. Moreover, the specific dimensions and shapes of individual crystallites play an important role both in the cyclic stress-strain response of these materials and in the formation of their interior structure in cyclic straining. Austenitic-ferritic duplex stainless steel, which is a kind of a natural composite, is a material of this type. The widespread interest in the application of duplex steels is caused by approximately doubled mechanical properties and equal corrosion properties, when compared with classical austenitic stainless steels. Fatigue resistance of these steels as well as the surface damage evolution in cyclic straining have been studied; however, much less is known about the internal substructure development in cyclic straining. In this study the dislocation arrangement in ferritic and austenitic grains of the austenitic-ferritic duplex steel alloyed with nitrogen and cyclically strained with two strain amplitudes, is reported and compared to the dislocation arrangement found in single and polycrystals of austenitic and ferritic materials of a similar composition and with the surface relief produced in cyclic plastic straining.

  1. Sub-structure of A Map Streamer

    NASA Astrophysics Data System (ADS)

    Liniger, M. A.; Davies, H. C.

    A study is undertaken of the sub-structure of an upper-level PV streamer that ap- proached the European Alps during the field phase of the Mesoscale Alpine Pro- gramme (MAP) in November 1999. The diagnosis is based upon a Lagrangian For- ward Projection (LFP) technique that can provide a spatial refinement of the opera- tional ECMWF analysis fields and relate the past Lagrangian history to these. The re- constructed fields capture several notable fine-scale features of the streamer's structure that include: -spiral arms of a vortex-like feature; -a richly structured western flank to the streamer comprising a deep primary fold surmounted by a significant secondary fold with an intermediate distinctive striation that extends back into the stratosphere. The features are not at variance with independent high-resolution satellite water vapour images and measurements gathered in a flight mission using an airbourne wa- ter vapour DIAL instrument, and hence lend a measure of credence to both the LFP approach and the DIAL measurements. Moreover the analysis sheds light on the evo- lution and dynamics of the streamer's vortices, the origin of the folds, and it also has implications for stratosphere-troposphere exchange and the accompanying chemical mixing.

  2. Finding Nonoverlapping Substructures of a Sparse Matrix

    SciTech Connect

    Pinar, Ali; Vassilevska, Virginia

    2005-08-11

    Many applications of scientific computing rely on computations on sparse matrices. The design of efficient implementations of sparse matrix kernels is crucial for the overall efficiency of these applications. Due to the high compute-to-memory ratio and irregular memory access patterns, the performance of sparse matrix kernels is often far away from the peak performance on a modern processor. Alternative data structures have been proposed, which split the original matrix A into A{sub d} and A{sub s}, so that A{sub d} contains all dense blocks of a specified size in the matrix, and A{sub s} contains the remaining entries. This enables the use of dense matrix kernels on the entries of A{sub d} producing better memory performance. In this work, we study the problem of finding a maximum number of nonoverlapping dense blocks in a sparse matrix, which is previously not studied in the sparse matrix community. We show that the maximum nonoverlapping dense blocks problem is NP-complete by using a reduction from the maximum independent set problem on cubic planar graphs. We also propose a 2/3-approximation algorithm that runs in linear time in the number of nonzeros in the matrix. This extended abstract focuses on our results for 2x2 dense blocks. However we show that our results can be generalized to arbitrary sized dense blocks, and many other oriented substructures, which can be exploited to improve the memory performance of sparse matrix operations.

  3. Forced unraveling of chromatin fibers with nonuniform linker DNA lengths

    NASA Astrophysics Data System (ADS)

    Ozer, Gungor; Collepardo-Guevara, Rosana; Schlick, Tamar

    2015-02-01

    The chromatin fiber undergoes significant structural changes during the cell's life cycle to modulate DNA accessibility. Detailed mechanisms of such structural transformations of chromatin fibers as affected by various internal and external conditions such as the ionic conditions of the medium, the linker DNA length, and the presence of linker histones, constitute an open challenge. Here we utilize Monte Carlo (MC) simulations of a coarse grained model of chromatin with nonuniform linker DNA lengths as found in vivo to help explain some aspects of this challenge. We investigate the unfolding mechanisms of chromatin fibers with alternating linker lengths of 26-62 bp and 44-79 bp using a series of end-to-end stretching trajectories with and without linker histones and compare results to uniform-linker-length fibers. We find that linker histones increase overall resistance of nonuniform fibers and lead to fiber unfolding with superbeads-on-a-string cluster transitions. Chromatin fibers with nonuniform linker DNA lengths display a more complex, multi-step yet smoother process of unfolding compared to their uniform counterparts, likely due to the existence of a more continuous range of nucleosome-nucleosome interactions. This finding echoes the theme that some heterogeneity in fiber component is biologically advantageous.

  4. The SEGUE K Giant Survey. III. Quantifying Galactic Halo Substructure

    NASA Astrophysics Data System (ADS)

    Janesh, William; Morrison, Heather L.; Ma, Zhibo; Rockosi, Constance; Starkenburg, Else; Xue, Xiang Xiang; Rix, Hans-Walter; Harding, Paul; Beers, Timothy C.; Johnson, Jennifer; Lee, Young Sun; Schneider, Donald P.

    2016-01-01

    We statistically quantify the amount of substructure in the Milky Way stellar halo using a sample of 4568 halo K giant stars at Galactocentric distances ranging over 5-125 kpc. These stars have been selected photometrically and confirmed spectroscopically as K giants from the Sloan Digital Sky Survey’s Sloan Extension for Galactic Understanding and Exploration project. Using a position-velocity clustering estimator (the 4distance) and a model of a smooth stellar halo, we quantify the amount of substructure in the halo, divided by distance and metallicity. Overall, we find that the halo as a whole is highly structured. We also confirm earlier work using blue horizontal branch (BHB) stars which showed that there is an increasing amount of substructure with increasing Galactocentric radius, and additionally find that the amount of substructure in the halo increases with increasing metallicity. Comparing to resampled BHB stars, we find that K giants and BHBs have similar amounts of substructure over equivalent ranges of Galactocentric radius. Using a friends-of-friends algorithm to identify members of individual groups, we find that a large fraction (˜33%) of grouped stars are associated with Sgr, and identify stars belonging to other halo star streams: the Orphan Stream, the Cetus Polar Stream, and others, including previously unknown substructures. A large fraction of sample K giants (more than 50%) are not grouped into any substructure. We find also that the Sgr stream strongly dominates groups in the outer halo for all except the most metal-poor stars, and suggest that this is the source of the increase of substructure with Galactocentric radius and metallicity.

  5. THE SEGUE K GIANT SURVEY. III. QUANTIFYING GALACTIC HALO SUBSTRUCTURE

    SciTech Connect

    Janesh, William; Morrison, Heather L.; Ma, Zhibo; Harding, Paul; Rockosi, Constance; Xue, Xiang Xiang; Rix, Hans-Walter; Beers, Timothy C.; Johnson, Jennifer; Lee, Young Sun; Schneider, Donald P.

    2016-01-10

    We statistically quantify the amount of substructure in the Milky Way stellar halo using a sample of 4568 halo K giant stars at Galactocentric distances ranging over 5–125 kpc. These stars have been selected photometrically and confirmed spectroscopically as K giants from the Sloan Digital Sky Survey’s Sloan Extension for Galactic Understanding and Exploration project. Using a position–velocity clustering estimator (the 4distance) and a model of a smooth stellar halo, we quantify the amount of substructure in the halo, divided by distance and metallicity. Overall, we find that the halo as a whole is highly structured. We also confirm earlier work using blue horizontal branch (BHB) stars which showed that there is an increasing amount of substructure with increasing Galactocentric radius, and additionally find that the amount of substructure in the halo increases with increasing metallicity. Comparing to resampled BHB stars, we find that K giants and BHBs have similar amounts of substructure over equivalent ranges of Galactocentric radius. Using a friends-of-friends algorithm to identify members of individual groups, we find that a large fraction (∼33%) of grouped stars are associated with Sgr, and identify stars belonging to other halo star streams: the Orphan Stream, the Cetus Polar Stream, and others, including previously unknown substructures. A large fraction of sample K giants (more than 50%) are not grouped into any substructure. We find also that the Sgr stream strongly dominates groups in the outer halo for all except the most metal-poor stars, and suggest that this is the source of the increase of substructure with Galactocentric radius and metallicity.

  6. Exploring Milkyway Halo Substructures with Large-Area Sky Surveys

    SciTech Connect

    Li, Ting

    2016-01-01

    Over the last two decades, our understanding of the Milky Way has been improved thanks to large data sets arising from large-area digital sky surveys. The stellar halo is now known to be inhabited by a variety of spatial and kinematic stellar substructures, including stellar streams and stellar clouds, all of which are predicted by hierarchical Lambda Cold Dark Matter models of galaxy formation. In this dissertation, we first present the analysis of spectroscopic observations of individual stars from the two candidate structures discovered using an M-giant catalog from the Two Micron All-Sky Survey. The follow-up observations show that one of the candidates is a genuine structure which might be associated with the Galactic Anticenter Stellar Structure, while the other one is a false detection due to the systematic photometric errors in the survey or dust extinction in low Galactic latitudes. We then presented the discovery of an excess of main sequence turn-off stars in the direction of the constellations of Eridanus and Phoenix from the first-year data of the Dark Energy Survey (DES) – a five-year, 5,000 deg2 optical imaging survey in the Southern Hemisphere. The Eridanus-Phoenix (EriPhe) overdensity is centered around l ~ 285° and b ~ -60° and the Poisson significance of the detection is at least 9σ. The EriPhe overdensity has a cloud-like morphology and the extent is at least ~ 4 kpc by ~ 3 kpc in projection, with a heliocentric distance of about d ~ 16 kpc. The EriPhe overdensity is morphologically similar to the previously-discovered Virgo overdensity and Hercules-Aquila cloud. These three overdensities lie along a polar plane separated by ~ 120° and may share a common origin. In addition to the scientific discoveries, we also present the work to improve the photometric calibration in DES using auxiliary calibration systems, since the photometric errors can cause false detection in first the halo substructure. We present a detailed description of the two

  7. Automatic identification of mobile and rigid substructures in molecular dynamics simulations and fractional structural fluctuation analysis.

    PubMed

    Martínez, Leandro

    2015-01-01

    The analysis of structural mobility in molecular dynamics plays a key role in data interpretation, particularly in the simulation of biomolecules. The most common mobility measures computed from simulations are the Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuations (RMSF) of the structures. These are computed after the alignment of atomic coordinates in each trajectory step to a reference structure. This rigid-body alignment is not robust, in the sense that if a small portion of the structure is highly mobile, the RMSD and RMSF increase for all atoms, resulting possibly in poor quantification of the structural fluctuations and, often, to overlooking important fluctuations associated to biological function. The motivation of this work is to provide a robust measure of structural mobility that is practical, and easy to interpret. We propose a Low-Order-Value-Optimization (LOVO) strategy for the robust alignment of the least mobile substructures in a simulation. These substructures are automatically identified by the method. The algorithm consists of the iterative superposition of the fraction of structure displaying the smallest displacements. Therefore, the least mobile substructures are identified, providing a clearer picture of the overall structural fluctuations. Examples are given to illustrate the interpretative advantages of this strategy. The software for performing the alignments was named MDLovoFit and it is available as free-software at: http://leandro.iqm.unicamp.br/mdlovofit.

  8. Mutations in Biosynthetic Enzymes for the Protein Linker Region of Chondroitin/Dermatan/Heparan Sulfate Cause Skeletal and Skin Dysplasias

    PubMed Central

    Mizumoto, Shuji; Yamada, Shuhei; Sugahara, Kazuyuki

    2015-01-01

    Glycosaminoglycans, including chondroitin, dermatan, and heparan sulfate, have various roles in a wide range of biological events such as cell signaling, cell proliferation, tissue morphogenesis, and interactions with various growth factors. Their polysaccharides covalently attach to the serine residues on specific core proteins through the common linker region tetrasaccharide, -xylose-galactose-galactose-glucuronic acid, which is produced through the stepwise addition of respective monosaccharides by four distinct glycosyltransferases. Mutations in the human genes encoding the glycosyltransferases responsible for the biosynthesis of the linker region tetrasaccharide cause a number of genetic disorders, called glycosaminoglycan linkeropathies, including Desbuquois dysplasia type 2, spondyloepimetaphyseal dysplasia, Ehlers-Danlos syndrome, and Larsen syndrome. This review focused on recent studies on genetic diseases caused by defects in the biosynthesis of the common linker region tetrasaccharide. PMID:26582078

  9. The importance of the cosmic web and halo substructure for power spectra

    NASA Astrophysics Data System (ADS)

    Pace, Francesco; Manera, Marc; Bacon, David J.; Crittenden, Robert; Percival, Will J.

    2015-11-01

    In this work, we study the relevance of the cosmic web and substructures on the matter and lensing power spectra measured from halo mock catalogues extracted from the N-body simulations. Since N-body simulations are computationally expensive, it is common to use faster methods that approximate the dark matter field as a set of haloes. In this approximation, we replace mass concentrations in N-body simulations by a spherically symmetric Navarro-Frenk-White halo density profile. We also consider the full mass field as the sum of two distinct fields: dark matter haloes (M > 9 × 1012 M⊙ h-1) and particles not included into haloes. Mock haloes reproduce well the matter power spectrum, but underestimate the lensing power spectrum on large and small scales. For sources at zs = 1 the lensing power spectrum is underestimated by up to 40 per cent at ℓ ≈ 104 with respect to the simulated haloes. The large-scale effect can be alleviated by combining the mock catalogue with the dark matter distribution outside the haloes. In addition, to evaluate the contribution of substructures we have smeared out the intrahalo substructures in an N-body simulation while keeping the halo density profiles unchanged. For the matter power spectrum the effect of this smoothing is only of the order of 5 per cent, but for lensing substructures and ellipticity are much more important: for ℓ ≈ 104 modifications to the internal structure contribute to 30 per cent of the total spectrum. These findings have important implications in the way mock catalogues have to be created, suggesting that some approximate methods currently used for galaxy surveys will be inadequate for future weak lensing surveys.

  10. Substructure and Dynamics of the Fornax Cluster

    NASA Astrophysics Data System (ADS)

    Drinkwater, Michael J.; Gregg, Michael D.; Colless, Matthew

    2001-02-01

    We present the first dynamical analysis of a galaxy cluster to include a large fraction of dwarf galaxies. Our sample of 108 Fornax Cluster members measured with the UK Schmidt Telescope FLAIR-II spectrograph contains 55 dwarf galaxies (15.5>bJ>18.0 or -16>MB>-13.5). Hα emission shows that 36%+/-8% of the dwarfs are star forming, twice the fraction implied by morphological classifications. The total sample has a mean velocity of 1493+/-36 km s-1 and a velocity dispersion of 374+/-26 km s-1. The dwarf galaxies form a distinct population: their velocity dispersion (429+/-41 km s-1) is larger than that of the giants (308+/-30 km s-1) at the 98% confidence level. This suggests that the dwarf population is dominated by infalling objects whereas the giants are virialized. The Fornax system has two components, the main Fornax Cluster centered on NGC 1399 with cz=1478 km s-1 and σcz=370 km s-1 and a subcluster centered 3° to the southwest including NGC 1316 with cz=1583 km s-1 and σcz=377 km s-1. This partition is preferred over a single cluster at the 99% confidence level. The subcluster, a site of intense star formation, is bound to Fornax and probably infalling toward the cluster core for the first time. We discuss the implications of this substructure for distance estimates of the Fornax Cluster. We determine the cluster mass profile using the method of Diaferio, which does not assume a virialized sample. The mass within a projected radius of 1.4 Mpc is (7+/-2)×1013 Msolar, and the mass-to-light ratio is 300+/-100 Msolar/Lsolar. The mass is consistent with values derived from the projected mass virial estimator and X-ray measurements at smaller radii.

  11. RESONANT CLUMPING AND SUBSTRUCTURE IN GALACTIC DISKS

    SciTech Connect

    Molloy, Matthew; Smith, Martin C.; Shen, Juntai; Evans, N. Wyn E-mail: msmith@shao.ac.cn E-mail: nwe@ast.cam.ac.uk

    2015-05-10

    We describe a method to extract resonant orbits from N-body simulations, exploiting the fact that they close in frames rotating with a constant pattern speed. Our method is applied to the N-body simulation of the Milky Way by Shen et al. This simulation hosts a massive bar, which drives strong resonances and persistent angular momentum exchange. Resonant orbits are found throughout the disk, both close to the bar and out to the very edges of the disk. Using Fourier spectrograms, we demonstrate that the bar is driving kinematic substructure even in the very outer parts of the disk. We identify two major orbit families in the outskirts of the disk, one of which makes significant contributions to the kinematic landscape, namely, the m:l = 3:−2 family, resonating with the bar. A mechanism is described that produces bimodal distributions of Galactocentric radial velocities at selected azimuths in the outer disk. It occurs as a result of the temporal coherence of particles on the 3:−2 resonant orbits, which causes them to arrive simultaneously at pericenter or apocenter. This resonant clumping, due to the in-phase motion of the particles through their epicycle, leads to both inward and outward moving groups that belong to the same orbital family and consequently produce bimodal radial velocity distributions. This is a possible explanation of the bimodal velocity distributions observed toward the Galactic anticenter by Liu et al. Another consequence is that transient overdensities appear and dissipate (in a symmetric fashion), resulting in a periodic pulsing of the disk’s surface density.

  12. Studies on the chemical stability and functional group compatibility of the benzoin photolabile safety-catch linker using an analytical construct.

    PubMed

    Cano, Montserrat; Ladlow, Mark; Balasubramanian, Shankar

    2002-01-01

    A chemical stability study of the benzoin photolabile safety-catch linker (BPSC) has been carried out using a dual-linker analytical construct to establish its compatibility with a range of commonly employed solid-phase reaction conditions. As a result of this study, the dithiane-protected benzoin linker was shown to be reactive only toward strong acids and fluoride nucleophile. Furthermore, a scan of diverse functional groups thought to be unstable toward the safety-catch removal conditions has also been carried out. These data should provide assistance in future utilization of the BPSC for syntheses.

  13. Structural Mechanisms of Nucleosome Recognition by Linker Histones.

    PubMed

    Zhou, Bing-Rui; Jiang, Jiansheng; Feng, Hanqiao; Ghirlando, Rodolfo; Xiao, T Sam; Bai, Yawen

    2015-08-20

    Linker histones bind to the nucleosome and regulate the structure of chromatin and gene expression. Despite more than three decades of effort, the structural basis of nucleosome recognition by linker histones remains elusive. Here, we report the crystal structure of the globular domain of chicken linker histone H5 in complex with the nucleosome at 3.5 Å resolution, which is validated using nuclear magnetic resonance spectroscopy. The globular domain sits on the dyad of the nucleosome and interacts with both DNA linkers. Our structure integrates results from mutation analyses and previous cross-linking and fluorescence recovery after photobleach experiments, and it helps resolve the long debate on structural mechanisms of nucleosome recognition by linker histones. The on-dyad binding mode of the H5 globular domain is different from the recently reported off-dyad binding mode of Drosophila linker histone H1. We demonstrate that linker histones with different binding modes could fold chromatin to form distinct higher-order structures.

  14. Gamma-ray probes of dark matter substructure

    SciTech Connect

    Campbell, Sheldon

    2014-06-24

    The substructure content of dark matter halos is interesting because it can be affected by complex galaxy physics and dark matter particle physics. However, observing the small scale structure of dark matter is a challenge. The subhalo abundance (mass function, minimum mass) and morphology (density profile, subhalo shape, subsubstructure) contain information about complex astrophysics (halo formation processes) and new exotic fundamental physics (dark matter interactions). Indirect detection of dark matter annihilation radiation (DMAR) in gamma rays may be the most direct method for observing small scale structure. I outline the ways in which gamma rays may probe halo substructure. If substructure is bountiful, it may be responsible for the eventual discovery of DMAR, for instance in galaxy clusters or the diffuse gamma-ray background. Otherwise, the observation of DMAR in places without much substructure, such as the Galactic center, would lead to strict limits on the properties of small scale structure. Properties of the gamma-ray angular power spectrum will also provide information or constraints on Milky Way halo substructure.

  15. Crystallization of Galectin-8 Linker Reveals Intricate Relationship between the N-terminal Tail and the Linker

    PubMed Central

    Si, Yunlong; Wang, Yue; Gao, Jin; Song, Chenyang; Feng, Shiqiong; Zhou, Yifa; Tai, Guihua; Su, Jiyong

    2016-01-01

    Galectin-8 (Gal-8) plays a significant role in normal immunological function as well as in cancer. This lectin contains two carbohydrate recognition domains (CRD) connected by a peptide linker. The N-terminal CRD determines ligand binding specificity, whereas the linker has been proposed to regulate overall Gal-8 function, including multimerization and biological activity. Here, we crystallized the Gal-8 N-terminal CRD with the peptide linker using a crystallization condition that contains Ni2+. The Ni2+ ion was found to be complexed between two CRDs via crystal packing contacts. The coordination between Ni2+ and Asp25 plays an indirect role in determining the structure of β-strand F0 and in influencing the linker conformation which could not be defined due to its dynamic nature. The linker was also shortened in situ and crystallized under a different condition, leading to a higher resolution structure refined to 1.08 Å. This crystal structure allowed definition of a short portion of the linker interacting with the Gal-8 N-terminal tail via ionic interactions and hydrogen bonds. Observation of two Gal-8 N-terminal CRD structures implies that the N-terminal tail and the linker may influence each other’s conformation. In addition, under specific crystallization conditions, glycerol could replace lactose and was observed at the carbohydrate binding site. However, glycerol did not show inhibition activity in hemagglutination assay. PMID:27973456

  16. Photocleavable linker for the patterning of bioactive molecules

    NASA Astrophysics Data System (ADS)

    Wegner, Seraphine V.; Sentürk, Oya I.; Spatz, Joachim P.

    2015-12-01

    Herein, we report the use of a versatile photocleavable nitrobenzyl linker to micropattern a wide variety of bioactive molecules and photorelease them on demand. On one end, the linker has an NHS group that can be coupled with any amine, such as peptides, proteins or amine-linkers, and on the other end an alkyne for convenient attachment to materials with an azide functional group. This linker was conjugated with NTA-amine or the cell adhesion peptide cRGD to enable straightforward patterning of His6-tagged proteins or cells, respectively, on PEGylated glass surfaces. This approach provides a practical way to control the presentation of a wide variety of bioactive molecules with high spatial and temporal resolution. The extent of photocleavage can also be controlled to tune the biomolecule density and degree of cell attachment to the surface.

  17. Preferentially quantized linker DNA lengths in Saccharomyces cerevisiae.

    PubMed

    Wang, Ji-Ping; Fondufe-Mittendorf, Yvonne; Xi, Liqun; Tsai, Guei-Feng; Segal, Eran; Widom, Jonathan

    2008-09-12

    The exact lengths of linker DNAs connecting adjacent nucleosomes specify the intrinsic three-dimensional structures of eukaryotic chromatin fibers. Some studies suggest that linker DNA lengths preferentially occur at certain quantized values, differing one from another by integral multiples of the DNA helical repeat, approximately 10 bp; however, studies in the literature are inconsistent. Here, we investigate linker DNA length distributions in the yeast Saccharomyces cerevisiae genome, using two novel methods: a Fourier analysis of genomic dinucleotide periodicities adjacent to experimentally mapped nucleosomes and a duration hidden Markov model applied to experimentally defined dinucleosomes. Both methods reveal that linker DNA lengths in yeast are preferentially periodic at the DNA helical repeat ( approximately 10 bp), obeying the forms 10n+5 bp (integer n). This 10 bp periodicity implies an ordered superhelical intrinsic structure for the average chromatin fiber in yeast.

  18. Linker histones in hormonal gene regulation.

    PubMed

    Vicent, G P; Wright, R H G; Beato, M

    2016-03-01

    In the present review, we summarize advances in our knowledge on the role of the histone H1 family of proteins in breast cancer cells, focusing on their response to progestins. Histone H1 plays a dual role in gene regulation by hormones, both as a structural component of chromatin and as a dynamic modulator of transcription. It contributes to hormonal regulation of the MMTV promoter by stabilizing a homogeneous nucleosome positioning, which reduces basal transcription whereas at the same time promoting progesterone receptor binding and nucleosome remodeling. These combined effects enhance hormone dependent gene transcription, which eventually requires H1 phosphorylation and displacement. Various isoforms of histone H1 have specific functions in differentiated breast cancer cells and compact nucleosomal arrays to different extents in vitro. Genome-wide studies show that histone H1 has a key role in chromatin dynamics of hormone regulated genes. A complex sequence of enzymatic events, including phosphorylation by CDK2, PARylation by PARP1 and the ATP-dependent activity of NURF, are required for H1 displacement and gene de-repression, as a prerequisite for further nucleosome remodeling. Similarly, during hormone-dependent gene repression a dedicated enzymatic mechanism controls H1 deposition at promoters by a complex containing HP1γ, LSD1 and BRG1, the ATPase of the BAF complex. Thus, a broader vision of the histone code should include histone H1, as the linker histone variants actively participate in the regulation of the chromatin structure. How modifications of the core histones tails affect H1 modifications and vice versa is one of the many questions that remains to be addressed to provide a more comprehensive view of the histone cross-talk mechanisms.

  19. EFFECT OF DARK MATTER HALO SUBSTRUCTURES ON GALAXY ROTATION CURVES

    SciTech Connect

    Roy, Nirupam

    2010-11-01

    In this paper, the effect of halo substructures on galaxy rotation curves is investigated using a simple model of dark matter clustering. A dark matter halo density profile is developed based only on the scale-free nature of clustering that leads to a statistically self-similar distribution of the substructures at the galactic scale. A semi-analytical method is used to derive rotation curves for such a clumpy dark matter density profile. It is found that the halo substructures significantly affect the galaxy velocity field. Based on the fractal geometry of the halo, this self-consistent model predicts a Navarro-Frenk-White-like rotation curve and a scale-free power spectrum of the rotation velocity fluctuations.

  20. ALMA Observations of Starless Core Substructure in Ophiuchus

    NASA Astrophysics Data System (ADS)

    Kirk, H.; Dunham, M. M.; Di Francesco, J.; Johnstone, D.; Offner, S. S. R.; Sadavoy, S. I.; Tobin, J. J.; Arce, H. G.; Bourke, T. L.; Mairs, S.; Myers, P. C.; Pineda, J. E.; Schnee, S.; Shirley, Y. L.

    2017-04-01

    Compact substructure is expected to arise in a starless core as mass becomes concentrated in the central region likely to form a protostar. Additionally, multiple peaks may form if fragmentation occurs. We present Atacama Large Millimeter/submillimeter Array (ALMA) Cycle 2 observations of 60 starless and protostellar cores in the Ophiuchus molecular cloud. We detect eight compact substructures which are > 15\\prime\\prime from the nearest Spitzer young stellar object. Only one of these has strong evidence for being truly starless after considering ancillary data, e.g., from Herschel and X-ray telescopes. An additional extended emission structure has tentative evidence for starlessness. The number of our detections is consistent with estimates from a combination of synthetic observations of numerical simulations and analytical arguments. This result suggests that a similar ALMA study in the Chamaeleon I cloud, which detected no compact substructure in starless cores, may be due to the peculiar evolutionary state of cores in that cloud.

  1. Shock induced deformation substructures in a copper bicrystal

    SciTech Connect

    Cao, Fang; Beyerlein, Irene J; Cerreta, Ellen K; Trujillo, Carl P; Gray Ill, George T; Sencer, Bulent H

    2008-01-01

    Controlled shock recovery experiments have been conducted to assess the role of shock pressure and orientation dependence on the substructure evolution of a [100]/[01{ovr 1}] copper bicrystal. Electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM) were utilized to characterize orientation variation and substructure evolution of the post-shock specimens. Well defined dislocation cell structures were displayed in both grains and the average cell size was observed to decrease with increasing shock pressure. Twinning was occasionally observed in the 5 GPa shocked [100] grain and became the dominant substructure at higher shock pressure. The stress and directional dependence of twinning in the bicrystal was analyzed with consideration of the energetically favorable dissociation of dislocations into Shockley partials and the stress-orientation effect on the partial width. Moreover, a critical 'tear apart' stress is proposed and a good agreement is obtained between the calculated value and the experimental observations.

  2. Linkers in the structural biology of protein-protein interactions.

    PubMed

    Reddy Chichili, Vishnu Priyanka; Kumar, Veerendra; Sivaraman, J

    2013-02-01

    Linkers or spacers are short amino acid sequences created in nature to separate multiple domains in a single protein. Most of them are rigid and function to prohibit unwanted interactions between the discrete domains. However, Gly-rich linkers are flexible, connecting various domains in a single protein without interfering with the function of each domain. The advent of recombinant DNA technology made it possible to fuse two interacting partners with the introduction of artificial linkers. Often, independent proteins may not exist as stable or structured proteins until they interact with their binding partner, following which they gain stability and the essential structural elements. Gly-rich linkers have been proven useful for these types of unstable interactions, particularly where the interaction is weak and transient, by creating a covalent link between the proteins to form a stable protein-protein complex. Gly-rich linkers are also employed to form stable covalently linked dimers, and to connect two independent domains that create a ligand-binding site or recognition sequence. The lengths of linkers vary from 2 to 31 amino acids, optimized for each condition so that the linker does not impose any constraints on the conformation or interactions of the linked partners. Various structures of covalently linked protein complexes have been described using X-ray crystallography, nuclear magnetic resonance and cryo-electron microscopy techniques. In this review, we evaluate several structural studies where linkers have been used to improve protein quality, to produce stable protein-protein complexes, and to obtain protein dimers.

  3. Dark Matter Substructure, Galaxy Assembly and Star Formation Histories

    NASA Astrophysics Data System (ADS)

    Simha, Vimal

    2011-01-01

    We use cosmological SPH simulations to study galaxy growth and the relationship between dark matter halos and the galaxies that form in them. We find that the distinction between central and satellite galaxies in our simulation is weaker than expected in simple models where only central galaxies are able to accrete mass and `receive' mergers of less massive systems. Instead, in our simulation, satellite galaxies continue to accrete gas and convert it to stars after halo mergers with a larger parent halo. Satellites in our simulation are 0.1-0.2 magnitudes bluer than in models that assume no gas accretion on to satellites after a halo merger (instantaneous `strangulation'), which is sufficient to shift galaxies across the boundary from the `red sequence' to the `blue cloud'. Subhalo abundance matching (SHAM) is a technique for assigning luminosities to simulated dark matter substructures by assuming a strictly monotonic relationship between luminosity and halo mass at the epoch of accretion. We carry out N-body and SPH simulations of a cosmological volume with identical initial conditions, finding that SHAM successfully matches the stellar masses and luminosities of SPH galaxies at a wide range of epochs, albeit with relatively small amounts of scatter. In our SPH simulations that include momentum driven winds, the results are more complex. We examine the relationship between halo assembly and star formation histories with the goal of extending SHAM to a wider domain of observables such as star formation history and colour. In order to guide efforts to fit star formation histories to observed colours or spectra, we investigate parametric fits to the star formation histories of SPH galaxies finding that some commonly used models fail to describe the star formation histories of SPH galaxies but other simple two parameter models achieve greater success.

  4. The SNAP-25 Linker as an Adaptation Toward Fast Exocytosis

    PubMed Central

    Nagy, Gábor; Milosevic, Ira; Mohrmann, Ralf; Wiederhold, Katrin; Walter, Alexander M.

    2008-01-01

    The assembly of four soluble N-ethylmaleimide-sensitive factor attachment protein receptor domains into a complex is essential for membrane fusion. In most cases, the four SNARE-domains are encoded by separate membrane-targeted proteins. However, in the exocytotic pathway, two SNARE-domains are present in one protein, connected by a flexible linker. The significance of this arrangement is unknown. We characterized the role of the linker in SNAP-25, a neuronal SNARE, by using overexpression techniques in synaptosomal-associated protein of 25 kDa (SNAP-25) null mouse chromaffin cells and fast electrophysiological techniques. We confirm that the palmitoylated linker-cysteines are important for membrane association. A SNAP-25 mutant without cysteines supported exocytosis, but the fusion rate was slowed down and the fusion pore duration prolonged. Using chimeric proteins between SNAP-25 and its ubiquitous homologue SNAP-23, we show that the cysteine-containing part of the linkers is interchangeable. However, a stretch of 10 hydrophobic and charged amino acids in the C-terminal half of the SNAP-25 linker is required for fast exocytosis and in its absence the calcium dependence of exocytosis is shifted toward higher concentrations. The SNAP-25 linker therefore might have evolved as an adaptation toward calcium triggering and a high rate of execution of the fusion process, those features that distinguish exocytosis from other membrane fusion pathways. PMID:18579690

  5. Linkers Having a Crucial Role in Antibody-Drug Conjugates.

    PubMed

    Lu, Jun; Jiang, Feng; Lu, Aiping; Zhang, Ge

    2016-04-14

    Antibody-drug conjugates (ADCs) comprised of a desirable monoclonal antibody, an active cytotoxic drug and an appropriate linker are considered to be an innovative therapeutic approach for targeted treatment of various types of tumors and cancers, enhancing the therapeutic parameter of the cytotoxic drug and reducing the possibility of systemic cytotoxicity. An appropriate linker between the antibody and the cytotoxic drug provides a specific bridge, and thus helps the antibody to selectively deliver the cytotoxic drug to tumor cells and accurately releases the cytotoxic drug at tumor sites. In addition to conjugation, the linkers maintain ADCs' stability during the preparation and storage stages of the ADCs and during the systemic circulation period. The design of linkers for ADCs is a challenge in terms of extracellular stability and intracellular release, and intracellular circumstances, such as the acid environment, the reducing environment and cathepsin, are considered as the catalysts to activate the triggers for initiating the cleavage of ADCs. This review discusses the linkers used in the clinical and marketing stages for ADCs and details the fracture modes of the linkers for the further development of ADCs.

  6. A Robust Control Design Framework for Substructure Models

    NASA Technical Reports Server (NTRS)

    Lim, Kyong B.

    1994-01-01

    A framework for designing control systems directly from substructure models and uncertainties is proposed. The technique is based on combining a set of substructure robust control problems by an interface stiffness matrix which appears as a constant gain feedback. Variations of uncertainties in the interface stiffness are treated as a parametric uncertainty. It is shown that multivariable robust control can be applied to generate centralized or decentralized controllers that guarantee performance with respect to uncertainties in the interface stiffness, reduced component modes and external disturbances. The technique is particularly suited for large, complex, and weakly coupled flexible structures.

  7. Substructures of the (252) ferrous martensite and their crystallographic significance

    SciTech Connect

    Wang Shidao |; Hei Zukun

    1999-04-23

    Many ferrous martensites have been found to possess a macroscopically invariant habit plane close to (252){sub f} and to exhibit complex and variable substructures that cannot be not only satisfactorily explained but also fully characterized so far. The present work attempts to examine the mechanism of occurrence of the complex substructures and their correlation to other crystallographic properties, esp. to the shape strain, on the basis of a new theory. The theory describes the atomic movements in the lattice change represented with the Bain distortion in the past.

  8. Galactic substructure and energetic neutrinos from the sun and earth.

    PubMed

    Koushiappas, Savvas M; Kamionkowski, Marc

    2009-09-18

    We consider the effects of Galactic substructure on energetic neutrinos from annihilation of weakly interacting massive particles that have been captured by the Sun and Earth. Substructure gives rise to a time-varying capture rate and thus to time variation in the annihilation rate and resulting energetic-neutrino flux. However, there may be a time lag between the capture and annihilation rates. The energetic-neutrino flux may then be determined by the density of dark matter in the Solar System's past trajectory, rather than the local density. The signature of such an effect may be sought in the ratio of the direct- to indirect-detection rates.

  9. A substructure coupling procedure applicable to general linear time-invariant dynamic systems

    NASA Technical Reports Server (NTRS)

    Howsman, T. G.; Craig, R. R., Jr.

    1984-01-01

    A substructure synthesis procedure applicable to structural systems containing general nonconservative terms is presented. In their final form, the nonself-adjoint substructure equations of motion are cast in state vector form through the use of a variational principle. A reduced-order mode for each substructure is implemented by representing the substructure as a combination of a small number of Ritz vectors. For the method presented, the substructure Ritz vectors are identified as a truncated set of substructure eigenmodes, which are typically complex, along with a set of generalized real attachment modes. The formation of the generalized attachment modes does not require any knowledge of the substructure flexible modes; hence, only the eigenmodes used explicitly as Ritz vectors need to be extracted from the substructure eigenproblem. An example problem is presented to illustrate the method.

  10. Oocyte-type linker histone B4 is required for transdifferentiation of somatic cells in vivo.

    PubMed

    Maki, Nobuyasu; Suetsugu-Maki, Rinako; Sano, Shozo; Nakamura, Kenta; Nishimura, Osamu; Tarui, Hiroshi; Del Rio-Tsonis, Katia; Ohsumi, Keita; Agata, Kiyokazu; Tsonis, Panagiotis A

    2010-09-01

    The ability to reprogram in vivo a somatic cell after differentiation is quite limited. One of the most impressive examples of such a process is transdifferentiation of pigmented epithelial cells (PECs) to lens cells during lens regeneration in newts. However, very little is known of the molecular events that allow newt cells to transdifferentiate. Histone B4 is an oocyte-type linker histone that replaces the somatic-type linker histone H1 during reprogramming mediated by somatic cell nuclear transfer (SCNT). We found that B4 is expressed and required during transdifferentiation of PECs. Knocking down of B4 decreased proliferation and increased apoptosis, which resulted in considerable smaller lens. Furthermore, B4 knockdown altered gene expression of key genes of lens differentiation and nearly abolished expression of gamma-crystallin. These data are the first to show expression of oocyte-type linker histone in somatic cells and its requirement in newt lens transdifferentiation and suggest that transdifferentiation in newts might share common strategies with reprogramming after SCNT.

  11. Effect of interdomain linker length on an antagonistic folding-unfolding equilibrium between two protein domains.

    PubMed

    Cutler, Thomas A; Mills, Brandon M; Lubin, David J; Chong, Lillian T; Loh, Stewart N

    2009-02-27

    Fusion of one protein domain with another is a common event in both evolution and protein engineering experiments. When insertion is at an internal site (e.g., a surface loop or turn), as opposed to one of the termini, conformational strain can be introduced into both domains. Strain is manifested by an antagonistic folding-unfolding equilibrium between the two domains, which we previously showed can be parameterized by a coupling free-energy term (DeltaG(X)). The extent of strain is predicted to depend primarily on the ratio of the N-to-C distance of the guest protein to the distance between ends of the surface loop in the host protein. Here, we test that hypothesis by inserting ubiquitin (Ub) into the bacterial ribonuclease barnase (Bn), using peptide linkers from zero to 10 amino acids each. DeltaG(X) values are determined by measuring the extent to which Co(2+) binding to an engineered site on the Ub domain destabilizes the Bn domain. All-atom, unforced Langevin dynamics simulations are employed to gain structural insight into the mechanism of mechanically induced unfolding. Experimental and computational results find that the two domains are structurally and energetically uncoupled when linkers are long and that DeltaG(X) increases with decreasing linker length. When the linkers are fewer than two amino acids, strain is so great that one domain unfolds the other. However, the protein is able to refold as dimers and higher-order oligomers. The likely mechanism is a three-dimensional domain swap of the Bn domain, which relieves conformational strain. The simulations suggest that an effective route to mechanical unfolding begins with disruption of the hydrophobic core of Bn near the Ub insertion site.

  12. A review of substructure coupling methods for dynamic analysis

    NASA Technical Reports Server (NTRS)

    Craig, R. R., Jr.; Chang, C. J.

    1976-01-01

    The state of the art is assessed in substructure coupling for dynamic analysis. A general formulation, which permits all previously described methods to be characterized by a few constituent matrices, is developed. Limited results comparing the accuracy of various methods are presented.

  13. Trans-dimensional Bayesian inference for gravitational lens substructures

    NASA Astrophysics Data System (ADS)

    Brewer, Brendon J.; Huijser, David; Lewis, Geraint F.

    2016-01-01

    We introduce a Bayesian solution to the problem of inferring the density profile of strong gravitational lenses when the lens galaxy may contain multiple dark or faint substructures. The source and lens models are based on a superposition of an unknown number of non-negative basis functions (or `blobs') whose form was chosen with speed as a primary criterion. The prior distribution for the blobs' properties is specified hierarchically, so the mass function of substructures is a natural output of the method. We use reversible jump Markov Chain Monte Carlo within Diffusive Nested Sampling to sample the posterior distribution and evaluate the marginal likelihood of the model, including the summation over the unknown number of blobs in the source and the lens. We demonstrate the method on two simulated data sets: one with a single substructure, and the other with 10. We also apply the method to the g-band image of the `Cosmic Horseshoe' system, and find evidence for more than zero substructures. However, these have large spatial extent and probably only point to misspecifications in the model (such as the shape of the smooth lens component or the point-spread function), which are difficult to guard against in full generality.

  14. Experimentally implementable criteria revealing substructures of genuine multipartite entanglement

    SciTech Connect

    Huber, Marcus; Schimpf, Hans; Gabriel, Andreas; Spengler, Christoph; Bruss, Dagmar; Hiesmayr, Beatrix C.

    2011-02-15

    We present a general framework that reveals substructures of genuine multipartite entanglement. Via simple inequalities it is possible to discriminate different sets of multipartite qubit states. These inequalities are beneficial regarding experimental examinations as only local measurements are required. Furthermore, the number of observables scales favorably with system size. In exemplary cases we demonstrate the noise resistance and discuss implementations.

  15. A Frequency-Domain Substructure System Identification Algorithm

    NASA Technical Reports Server (NTRS)

    Blades, Eric L.; Craig, Roy R., Jr.

    1996-01-01

    A new frequency-domain system identification algorithm is presented for system identification of substructures, such as payloads to be flown aboard the Space Shuttle. In the vibration test, all interface degrees of freedom where the substructure is connected to the carrier structure are either subjected to active excitation or are supported by a test stand with the reaction forces measured. The measured frequency-response data is used to obtain a linear, viscous-damped model with all interface-degree of freedom entries included. This model can then be used to validate analytical substructure models. This procedure makes it possible to obtain not only the fixed-interface modal data associated with a Craig-Bampton substructure model, but also the data associated with constraint modes. With this proposed algorithm, multiple-boundary-condition tests are not required, and test-stand dynamics is accounted for without requiring a separate modal test or finite element modeling of the test stand. Numerical simulations are used in examining the algorithm's ability to estimate valid reduced-order structural models. The algorithm's performance when frequency-response data covering narrow and broad frequency bandwidths is used as input is explored. Its performance when noise is added to the frequency-response data and the use of different least squares solution techniques are also examined. The identified reduced-order models are also compared for accuracy with other test-analysis models and a formulation for a Craig-Bampton test-analysis model is also presented.

  16. Chemical Substructure Searching: Comparing Three Commercially Available Databases.

    ERIC Educational Resources Information Center

    Wagner, A. Ben

    1986-01-01

    Compares the differences in coverage and utility of three substructure databases--Chemical Abstracts, Index Chemicus, and Chemical Information System's Nomenclature Search System. The differences between Chemical Abstracts with two different vendors--STN International and Questel--are described and a summary guide for choosing between databases is…

  17. Evolutionarily conserved substrate substructures for automated annotation of enzyme superfamilies.

    PubMed

    Chiang, Ranyee A; Sali, Andrej; Babbitt, Patricia C

    2008-08-01

    The evolution of enzymes affects how well a species can adapt to new environmental conditions. During enzyme evolution, certain aspects of molecular function are conserved while other aspects can vary. Aspects of function that are more difficult to change or that need to be reused in multiple contexts are often conserved, while those that vary may indicate functions that are more easily changed or that are no longer required. In analogy to the study of conservation patterns in enzyme sequences and structures, we have examined the patterns of conservation and variation in enzyme function by analyzing graph isomorphisms among enzyme substrates of a large number of enzyme superfamilies. This systematic analysis of substrate substructures establishes the conservation patterns that typify individual superfamilies. Specifically, we determined the chemical substructures that are conserved among all known substrates of a superfamily and the substructures that are reacting in these substrates and then examined the relationship between the two. Across the 42 superfamilies that were analyzed, substantial variation was found in how much of the conserved substructure is reacting, suggesting that superfamilies may not be easily grouped into discrete and separable categories. Instead, our results suggest that many superfamilies may need to be treated individually for analyses of evolution, function prediction, and guiding enzyme engineering strategies. Annotating superfamilies with these conserved and reacting substructure patterns provides information that is orthogonal to information provided by studies of conservation in superfamily sequences and structures, thereby improving the precision with which we can predict the functions of enzymes of unknown function and direct studies in enzyme engineering. Because the method is automated, it is suitable for large-scale characterization and comparison of fundamental functional capabilities of both characterized and uncharacterized

  18. DNA Linker Mediated Assembly of Gold Nanoparticles Superlattice

    NASA Astrophysics Data System (ADS)

    Xiong, Huiming; Sfeir, Mattew Y.; van der Lelie, Daniel; Gang, Oleg

    2011-03-01

    A BCC (body-centered-cubic) crystalline phase forms when flexible ssDNA linkers are added to the mixture of two types of dispersed, ssDNAs capped gold nanocolloids which are mutually non-complementary but complementary to the respective ends of the linker DNA. The state diagram of DNA linker mediated nanoparticle assemblies has been experimentally investigated and constructed by using in-situ small angle x-ray scattering. The optically active three-dimensional superlattice containing plasmonic particles and DNA-encoded chromophors were further fabricated using this approach. We investigated structural tunability and corresponding optical response of the multicomponent superlattices. Support from the U. S. DOE Office of Science and Office of Basic Energy Sciences under contract No. DE-AC-02-98CH10886 and Shanghai Pujiang Program (10PJ1405400) is appreciated.

  19. Role of the external NH2 linker on the conformation of surface immobilized single strand DNA probes and their SERS detection

    NASA Astrophysics Data System (ADS)

    He, Lijie; Langlet, Michel; Stambouli, Valerie

    2017-03-01

    The conformation and topological properties of DNA single strand probe molecules attached on solid surfaces are important, notably for the performances of devices such as biosensors. Commonly, the DNA probes are tethered to the surface using external linkers such as NH2. In this study, the role and influence of this amino-linker on the immobilization way and conformation of DNA probes on Ag nanoparticle surface is emphasized using Surface Enhanced Raman Spectroscopy (SERS). We compare the SERS spectra and their reproducibility in the case of two groups of DNA polybase probes which are polyA, polyC, polyT, and polyG. In the first group, the polybases exhibit an external NH2 functional linker while in the second group the polybases are NH2-free. The results show that the reproducibility of SERS spectra is enhanced in the case of the first group. It leads us to propose two models of polybase conformation on Ag surface according to the presence or the absence of the external NH2 linker. In the presence of the NH2 external linker, the latter would act as a major anchoring point. As a result, the polybases are much ordered with a less random orientation than in the case of NH2-free polybases. Consequently, in view of further in situ hybridization for biosensing applications, it is strongly recommended to use NH2 linker functionalized DNA probes.

  20. Cold Dark Matter Substructure and Galactic Disks I: Morphological Signatures of Hierarchical SatelliteAccretion

    SciTech Connect

    Kazantzidis, Stelios; Bullock, James S.; Zentner, Andrew R.; Kravtsov, Andrey V.; Moustakas, Leonidas A.

    2007-12-03

    We conduct a series of high-resolution, fully self-consistent dissipation less N-body simulations to investigate the cumulative effect of substructure mergers onto thin disk galaxies in the context of the {Lambda}CDM paradigm of structure formation. Our simulation campaign is based on a hybrid approach combining cosmological simulations and controlled numerical experiments. Substructure mass functions, orbital distributions, internal structures, and accretion times are culled directly from cosmological simulations of galaxy-sized cold dark matter (CDM) halos. We demonstrate that accretions of massive subhalos onto the central regions of host halos, where the galactic disk resides, since z {approx} 1 should be common occurrences. In contrast, extremely few satellites in present-day CDM halos are likely to have a significant impact on the disk structure. This is due to the fact that massive subhalos with small orbital pericenters that are most capable of strongly perturbing the disk become either tidally disrupted or suffer substantial mass loss prior to z = 0. One host halo merger history is subsequently used to seed controlled N-body experiments of repeated satellite impacts on an initially-thin Milky Way-type disk galaxy. These simulations track the effects of six dark matter substructures, with initial masses in the range {approx} (0.7-2) x 10{sup 10} M{sub {circle_dot}} ({approx} 20-60% of the disk mass), crossing the disk in the past {approx} 8 Gyr. We show that these accretion events produce several distinctive observational signatures in the stellar disk including: a long-lived, low-surface brightness, ring-like feature in the outskirts; a significant flare; a central bar; and faint filamentary structures that (spuriously) resemble tidal streams in configuration space. The final distribution of disk stars exhibits a complex vertical structure that is well-described by a standard 'thin-thick' disk decomposition, where the 'thick' disk component has emerged

  1. Phenotypic variation of erythrocyte linker histone H1.c in a pheasant (Phasianus colchicus L.) population.

    PubMed

    Kowalski, Andrzej; Pa Yga, Jan; Górnicka-Michalska, Ewa; Bernacki, Zenon; Adamski, Marek

    2010-07-01

    Our goal was to characterize a phenotypic variation of the pheasant erythrocyte linker histone subtype H1.c. By using two-dimensional polyacrylamide gel electrophoresis three histone H1.c phenotypes were identified. The differently migrating allelic variants H1.c1 and H1.c2 formed either two homozygous phenotypes, c1 and c2, or a single heterozygous phenotype, c1c2. In the pheasant population screened, birds with phenotype c2 were the most common (frequency 0.761) while individuals with phenotype c1 were rare (frequency 0.043).

  2. Floating substructure flexibility of large-volume 10MW offshore wind turbine platforms in dynamic calculations

    NASA Astrophysics Data System (ADS)

    Borg, Michael; Melchior Hansen, Anders; Bredmose, Henrik

    2016-09-01

    Designing floating substructures for the next generation of 10MW and larger wind turbines has introduced new challenges in capturing relevant physical effects in dynamic simulation tools. In achieving technically and economically optimal floating substructures, structural flexibility may increase to the extent that it becomes relevant to include in addition to the standard rigid body substructure modes which are typically described through linear radiation-diffraction theory. This paper describes a method for the inclusion of substructural flexibility in aero-hydro-servo-elastic dynamic simulations for large-volume substructures, including wave-structure interactions, to form the basis of deriving sectional loads and stresses within the substructure. The method is applied to a case study to illustrate the implementation and relevance. It is found that the flexible mode is significantly excited in an extreme event, indicating an increase in predicted substructure internal loads.

  3. Simple models for rope substructure mechanics: application to electro-mechanical lifts

    NASA Astrophysics Data System (ADS)

    Herrera, I.; Kaczmarczyk, S.

    2016-05-01

    Mechanical systems modelled as rigid mass elements connected by tensioned slender structural members such as ropes and cables represent quite common substructures used in lift engineering and hoisting applications. Special interest is devoted by engineers and researchers to the vibratory response of such systems for optimum performance and durability. This paper presents simplified models that can be employed to determine the natural frequencies of systems having substructures of two rigid masses constrained by tensioned rope/cable elements. The exact solution for free un-damped longitudinal displacement response is discussed in the context of simple two-degree-of-freedom models. The results are compared and the influence of characteristics parameters such as the ratio of the average mass of the two rigid masses with respect to the rope mass and the deviation ratio of the two rigid masses with respect to the average mass is analyzed. This analysis gives criteria for the application of such simplified models in complex elevator and hoisting system configurations.

  4. RINGED SUBSTRUCTURE AND A GAP AT 1 au IN THE NEAREST PROTOPLANETARY DISK

    SciTech Connect

    Andrews, Sean M.; Wilner, David J.; Bai, Xue-Ning; Öberg, Karin I.; Ricci, Luca; Zhu, Zhaohuan; Birnstiel, Tilman; Carpenter, John M.; Pérez, Laura M.; Hughes, A. Meredith; Isella, Andrea

    2016-04-01

    We present long baseline Atacama Large Millimeter/submillimeter Array (ALMA) observations of the 870 μm continuum emission from the nearest gas-rich protoplanetary disk, around TW Hya, that trace millimeter-sized particles down to spatial scales as small as 1 au (20 mas). These data reveal a series of concentric ring-shaped substructures in the form of bright zones and narrow dark annuli (1–6 au) with modest contrasts (5%–30%). We associate these features with concentrations of solids that have had their inward radial drift slowed or stopped, presumably at local gas pressure maxima. No significant non-axisymmetric structures are detected. Some of the observed features occur near temperatures that may be associated with the condensation fronts of major volatile species, but the relatively small brightness contrasts may also be a consequence of magnetized disk evolution (the so-called zonal flows). Other features, particularly a narrow dark annulus located only 1 au from the star, could indicate interactions between the disk and young planets. These data signal that ordered substructures on ∼au scales can be common, fundamental factors in disk evolution and that high-resolution microwave imaging can help characterize them during the epoch of planet formation.

  5. Towards an understanding of the correlations in jet substructure

    SciTech Connect

    Adams, D.; Arce, A.; Asquith, L.; Backovic, M.; Barillari, T.; Berta, P.; Bertolini, D.; Buckley, A.; Butterworth, J.; Camacho Toro, R.  C.; Caudron, J.; Chien, Y. -T.; Cogan, J.; Cooper, B.; Curtin, D.; Debenedetti, C.; Dolen, J.; Eklund, M.; El Hedri, S.; Ellis, S.  D.; Embry, T.; Ferencek, D.; Ferrando, J.; Fleischmann, S.; Freytsis, M.; Giulini, M.; Han, Z.; Hare, D.; Harris, P.; Hinzmann, A.; Hoing, R.; Hornig, A.; Jankowiak, M.; Johns, K.; Kasieczka, G.; Kogler, R.; Lampl, W.; Larkoski, A.  J.; Lee, C.; Leone, R.; Loch, P.; Lopez Mateos, D.; Lou, H. K.; Low, M.; Maksimovic, P.; Marchesini, I.; Marzani, S.; Masetti, L.; McCarthy, R.; Menke, S.; Miller, D.  W.; Mishra, K.; Nachman, B.; Nef, P.; O’Grady, F.  T.; Ovcharova, A.; Picazio, A.; Pollard, C.; Potter-Landua, B.; Potter, C.; Rappoccio, S.; Rojo, J.; Rutherfoord, J.; Salam, G.  P.; Schabinger, R.  M.; Schwartzman, A.; Schwartz, M.  D.; Shuve, B.; Sinervo, P.; Soper, D.; Sosa Corral, D.  E.; Spannowsky, M.; Strauss, E.; Swiatlowski, M.; Thaler, J.; Thomas, C.; Thompson, E.; Tran, N.  V.; Tseng, J.; Usai, E.; Valery, L.; Veatch, J.; Vos, M.; Waalewijn, W.; Wacker, J.; Young, C.

    2015-09-09

    Over the past decade, a large number of jet substructure observables have been proposed in the literature, and explored at the LHC experiments. Such observables attempt to utilize the internal structure of jets in order to distinguish those initiated by quarks, gluons, or by boosted heavy objects, such as top quarks and W bosons. This report, originating from and motivated by the BOOST2013 workshop, presents original particle-level studies that aim to improve our understanding of the relationships between jet substructure observables, their complementarity, and their dependence on the underlying jet properties, particularly the jet radius and jet transverse momentum. This is explored in the context of quark/gluon discrimination, boosted W boson tagging and boosted top quark tagging.

  6. Towards an understanding of the correlations in jet substructure

    DOE PAGES

    Adams, D.; Arce, A.; Asquith, L.; ...

    2015-09-09

    Over the past decade, a large number of jet substructure observables have been proposed in the literature, and explored at the LHC experiments. Such observables attempt to utilize the internal structure of jets in order to distinguish those initiated by quarks, gluons, or by boosted heavy objects, such as top quarks and W bosons. This report, originating from and motivated by the BOOST2013 workshop, presents original particle-level studies that aim to improve our understanding of the relationships between jet substructure observables, their complementarity, and their dependence on the underlying jet properties, particularly the jet radius and jet transverse momentum. Thismore » is explored in the context of quark/gluon discrimination, boosted W boson tagging and boosted top quark tagging.« less

  7. Fold Recognition Using Sequence Fingerprints of Protein Local Substructures

    SciTech Connect

    Kryshtafovych, A A; Hvidsten, T; Komorowski, J; Fidelis, K

    2003-06-04

    A protein local substructure (descriptor) is a set of several short non-overlapping fragments of the polypeptide chain. Each descriptor describes local environment of a particular residue and includes only those segments that are located in the proximity of this residue. Similar descriptors from the representative set of proteins were analyzed to reveal links between the substructures and sequences of their segments. Using detected sequence-based fingerprints specific geometrical conformations are assigned to new sequences. The ability of the approach to recognize correct SCOP folds was tested on 273 sequences from the 49 most popular folds. Good predictions were obtained in 85% of cases. No performance drop was observed with decreasing sequence similarity between target sequences and sequences from the training set of proteins.

  8. Evolving Flare Ribbon Small-Scale Substructure: A Second Candidate

    NASA Astrophysics Data System (ADS)

    Roegge, Alissa; Brannon, Sean

    2017-01-01

    We present preliminary analysis on imaging and spectroscopic observations from the Interface Region Imaging Spectrograph (IRIS) of the evolution of the flare ribbon in the SOL2014-06-22T13:08 B-class flare event, at high spatial resolution and time cadence. IRIS is a solar observation satellite containing a high frame rate ultraviolet imaging spectrometer. This work continues the work started in Brannon et al 2015 by searching for small-scale substructure within flare ribbons, which manifest themselves as coherent quasiperiodic oscillations in both position and Doppler velocities. Using IRIS observations from October 2013 to June 2016, we selected candidate observations on the basis of physical characteristics, Si IV intensity, and shift in doppler velocity. In addition to our preliminary analysis and images, we present our techniques that can be used to find further observations also containing the periodic oscillations, and other small-substructure.

  9. Fossil group origins. VII. Galaxy substructures in fossil systems

    NASA Astrophysics Data System (ADS)

    Zarattini, S.; Girardi, M.; Aguerri, J. A. L.; Boschin, W.; Barrena, R.; del Burgo, C.; Castro-Rodriguez, N.; Corsini, E. M.; D'Onghia, E.; Kundert, A.; Méndez-Abreu, J.; Sánchez-Janssen, R.

    2016-02-01

    Context. Fossil groups (FG) are expected to be the final product of galaxy merging within galaxy groups. In simulations, they are predicted to assemble their mass at high redshift. This early formation allows for the innermost M∗ galaxies to merge into a massive central galaxy. Then, they are expected to maintain their fossil status because of the few interactions with the large-scale structure. In this context, the magnitude gap between the two brightest galaxies of the system is considered a good indicator of its dynamical status. As a consequence, the systems with the largest gaps should be dynamically relaxed. Aims: In order to examine the dynamical status of these systems, we systematically analyze, for the first time, the presence of galaxy substructures in a sample of 12 spectroscopically-confirmed fossil systems with redshift z ≤ 0.25. Methods: We apply a number of tests to investigate the substructure in fossil systems in the two-dimensional space of projected positions out to R200. Moreover, for a subsample of five systems with at least 30 spectroscopically-confirmed members we also analyze the substructure in the velocity and in the three-dimensional velocity-position spaces. Additionally, we look for signs of recent mergers in the regions around the central galaxies. Results: We find that an important fraction of fossil systems show substructure. The fraction depends critically on the adopted test, since each test is more sensitive to a particular type of substructure. Conclusions: Our interpretation of the results is that fossil systems are not, in general, as relaxed as expected from simulations. Our sample of 12 spectroscopically-confirmed fossil systems need to be extended to compute an accurate fraction, but our conclusion is that this fraction is similar to the fraction of substructure detected in nonfossil clusters. This result points out that the magnitude gap alone is not a good indicator of the dynamical status of a system. However, the

  10. Substructure of the inner core of the Earth.

    PubMed Central

    Herndon, J M

    1996-01-01

    The rationale is disclosed for a substructure within the Earth's inner core, consisting of an actinide subcore at the center of the Earth, surrounded by a subshell composed of the products of nuclear fission and radioactive decay. Estimates are made as to possible densities, physical dimensions, and chemical compositions. The feasibility for self-sustaining nuclear fission within the subcore is demonstrated, and implications bearing on the structure and geodynamic activity of the inner core are discussed. PMID:11607625

  11. Modal Substructuring of Geometrically Nonlinear Finite-Element Models

    SciTech Connect

    Kuether, Robert J.; Allen, Matthew S.; Hollkamp, Joseph J.

    2015-12-21

    The efficiency of a modal substructuring method depends on the component modes used to reduce each subcomponent model. Methods such as Craig–Bampton have been used extensively to reduce linear finite-element models with thousands or even millions of degrees of freedom down orders of magnitude while maintaining acceptable accuracy. A novel reduction method is proposed here for geometrically nonlinear finite-element models using the fixed-interface and constraint modes of the linearized system to reduce each subcomponent model. The geometric nonlinearity requires an additional cubic and quadratic polynomial function in the modal equations, and the nonlinear stiffness coefficients are determined by applying a series of static loads and using the finite-element code to compute the response. The geometrically nonlinear, reduced modal equations for each subcomponent are then coupled by satisfying compatibility and force equilibrium. This modal substructuring approach is an extension of the Craig–Bampton method and is readily applied to geometrically nonlinear models built directly within commercial finite-element packages. The efficiency of this new approach is demonstrated on two example problems: one that couples two geometrically nonlinear beams at a shared rotational degree of freedom, and another that couples an axial spring element to the axial degree of freedom of a geometrically nonlinear beam. The nonlinear normal modes of the assembled models are compared with those of a truth model to assess the accuracy of the novel modal substructuring approach.

  12. Modal Substructuring of Geometrically Nonlinear Finite-Element Models

    DOE PAGES

    Kuether, Robert J.; Allen, Matthew S.; Hollkamp, Joseph J.

    2015-12-21

    The efficiency of a modal substructuring method depends on the component modes used to reduce each subcomponent model. Methods such as Craig–Bampton have been used extensively to reduce linear finite-element models with thousands or even millions of degrees of freedom down orders of magnitude while maintaining acceptable accuracy. A novel reduction method is proposed here for geometrically nonlinear finite-element models using the fixed-interface and constraint modes of the linearized system to reduce each subcomponent model. The geometric nonlinearity requires an additional cubic and quadratic polynomial function in the modal equations, and the nonlinear stiffness coefficients are determined by applying amore » series of static loads and using the finite-element code to compute the response. The geometrically nonlinear, reduced modal equations for each subcomponent are then coupled by satisfying compatibility and force equilibrium. This modal substructuring approach is an extension of the Craig–Bampton method and is readily applied to geometrically nonlinear models built directly within commercial finite-element packages. The efficiency of this new approach is demonstrated on two example problems: one that couples two geometrically nonlinear beams at a shared rotational degree of freedom, and another that couples an axial spring element to the axial degree of freedom of a geometrically nonlinear beam. The nonlinear normal modes of the assembled models are compared with those of a truth model to assess the accuracy of the novel modal substructuring approach.« less

  13. Population substructure and isolation by distance in three continental regions.

    PubMed

    Eller, E

    1999-02-01

    Isolation by distance and divergence from a shared population history are two sources of population substructure. Isolation by distance erases population history as populations approach migration-drift equilibrium, while diverging populations descended from a single ancestral population will accumulate genetic differences with time. Here I investigate how much of the worldwide genetic diversity from Jorde et al.'s ([1997] Proc. Natl. Acad. Sci. USA 94:3100-3103) 60 tetranucleotide short tandem repeat (STR) data can be explained by isolation by distance. I use Slatkin's measure of population substructure, R(ST), principal components analyses, and Mantel tests to investigate the pattern of genetic diversity at both the intercontinental and intracontinental levels. Geographic distance accounts for almost 60% of world-wide interpopulation genetic relationships. Within continents, the correlations are less, although not significantly so because of wide confidence intervals. These results suggest that populations have not reached migration-drift equilibrium and that there is information in STR data to reconstruct population history. The level of population substructure worldwide is consistent with previous observations, but at the intracontinental level substructure is less. When one examines diversity against distance from the centroid, one sees excess heterozygosity in Africa, a pattern also noted by Stoneking et al. ([1998] Genome Research 7:1061-1071). A larger effective population size in Africa could explain the excess diversity. Greater gene flow in Africa is an unlikely explanation because the African R(ST) value is slightly larger than the Asian and European R(ST)s, pointing to less gene flow and greater substructure among African populations. Furthermore, there are differences in patterns between heterozygosity and allele size variance. Heterozygosity has a higher correlation with distance from the centroid than does allele size variance, and this may reflect

  14. Substructure in the circumstellar disk around the young star AU Microscopii.

    PubMed

    Liu, Michael C

    2004-09-03

    Keck adaptive optics imaging with a physical resolution of 0.4 astronomical units (AU) resolves the inner (15 to 80 AU) disk of AU Microscopii (AU Mic, GJ 803, HD 197481), the nearest known scattered light disk to Earth. The inner disk is asymmetric and possesses a sharp change in structure at 35 AU. The disk also shows spatially localized enhancements and deficits at 25- to 40-AU separations. The overall morphology points to the influence of unseen larger bodies and resembles structures expected from recent planet formation. AU Mic is coeval with the archetypical debris disk system beta Pictoris, and the similarities between their two disks point to synchronous disk evolution. Multiple indications of substructure appear to be common in circumstellar disks at an age of approximately 12 million years.

  15. Offshore deck to substructure mating system and method

    SciTech Connect

    Datta, B.N.; Baldwin, R.L.; Allen, J.D.

    1993-06-15

    An offshore platform, in combination, a deck for installation to be supported by a substructure is described including a plurality of upstanding column members, said deck including a corresponding plurality of depending legs, the improvement characterized by: at least one of said legs including a stabbing tip assembly for engagement with a corresponding column member, said stabbing tip assembly comprising an outer body for engagement with said column member to transfer permanent weight of said deck to said column member, a generally vertically movable locating pin disposed in said body for movement to stab into receiver means including means forming a receptacle on said column member for locating said dock with respect to said column member, and resilient means supported by said body for accommodating lateral and vertically-imposed loads acting between said column member and said leg during placement of said deck on said substructure to minimize the imposition of peak forces on said deck and said substructure; said receiver means comprising a generally cylindrical receiver shoe forming said receptacle, said shoe comprising part of a jack assembly supported on said column member and said shoe being operable to be moved to a position to permit contact of said leg with said column member to provide supporting relationship therebetween; and said jack assembly comprising a generally cylindrical body member supported on said column member and forming a chamber with said shoe for receiving particulate material to support said shoe in a first position for receiving said locating pin, said shoe being movable to a second position in response to removing said particulate material from said chamber to permit movement of said leg into engagement with said body member.

  16. Fast antibody fragment motion: flexible linkers act as entropic spring.

    PubMed

    Stingaciu, Laura R; Ivanova, Oxana; Ohl, Michael; Biehl, Ralf; Richter, Dieter

    2016-03-29

    A flexible linker region between three fragments allows antibodies to adjust their binding sites to an antigen or receptor. Using Neutron Spin Echo Spectroscopy we observed fragment motion on a timescale of 7 ns with motional amplitudes of about 1 nm relative to each other. The mechanistic complexity of the linker region can be described by a spring model with Brownian motion of the fragments in a harmonic potential. Displacements, timescale, friction and force constant of the underlying dynamics are accessed. The force constant exhibits a similar strength to an entropic spring, with friction of the fragment matching the unbound state. The observed fast motions are fluctuations in pre-existing equilibrium configurations. The Brownian motion of domains in a harmonic potential is the appropriate model to examine functional hinge motions dependent on the structural topology and highlights the role of internal forces and friction to function.

  17. Rheology of semiflexible bundle networks with transient linkers.

    PubMed

    Müller, Kei W; Bruinsma, Robijn F; Lieleg, Oliver; Bausch, Andreas R; Wall, Wolfgang A; Levine, Alex J

    2014-06-13

    We present a theoretical and computational analysis of the rheology of networks made up of bundles of semiflexible filaments bound by transient cross-linkers. Such systems are ubiquitous in the cytoskeleton and can be formed in vitro using filamentous actin and various cross-linkers. We find that their high-frequency rheology is characterized by a scaling behavior that is quite distinct from that of networks of the well-studied single semiflexible filaments. This regime can be understood theoretically in terms of a length-scale-dependent bending modulus for bundles. Next, we observe new dissipative dynamics associated with the shear-induced disruption of the network at intermediate frequencies. Finally, at low frequencies, we encounter a region of non-Newtonian rheology characterized by power-law scaling. This regime is dominated by bundle dissolution and large-scale rearrangements of the network driven by equilibrium thermal fluctuations.

  18. Fast antibody fragment motion: flexible linkers act as entropic spring

    SciTech Connect

    Stingaciu, Laura R.; Ivanova, Oxana; Ohl, Michael; Biehl, Ralf; Richter, Dieter

    2016-03-29

    A flexible linker region between three fragments allows antibodies to adjust their binding sites to an antigen or receptor. Using Neutron Spin Echo Spectroscopy we observed fragment motion on a timescale of 7 ns with motional amplitudes of about 1 nm relative to each other. The mechanistic complexity of the linker region can be described by a spring model with Brownian motion of the fragments in a harmonic potential. Displacements, timescale, friction and force constant of the underlying dynamics are accessed. The force constant exhibits a similar strength to an entropic spring, with friction of the fragment matching the unbound state. The observed fast motions are fluctuations in pre-existing equilibrium configurations. In conclusion, the Brownian motion of domains in a harmonic potential is the appropriate model to examine functional hinge motions dependent on the structural topology and highlights the role of internal forces and friction to function.

  19. Fast antibody fragment motion: flexible linkers act as entropic spring

    DOE PAGES

    Stingaciu, Laura R.; Ivanova, Oxana; Ohl, Michael; ...

    2016-03-29

    A flexible linker region between three fragments allows antibodies to adjust their binding sites to an antigen or receptor. Using Neutron Spin Echo Spectroscopy we observed fragment motion on a timescale of 7 ns with motional amplitudes of about 1 nm relative to each other. The mechanistic complexity of the linker region can be described by a spring model with Brownian motion of the fragments in a harmonic potential. Displacements, timescale, friction and force constant of the underlying dynamics are accessed. The force constant exhibits a similar strength to an entropic spring, with friction of the fragment matching the unboundmore » state. The observed fast motions are fluctuations in pre-existing equilibrium configurations. In conclusion, the Brownian motion of domains in a harmonic potential is the appropriate model to examine functional hinge motions dependent on the structural topology and highlights the role of internal forces and friction to function.« less

  20. Fast antibody fragment motion: flexible linkers act as entropic spring

    PubMed Central

    Stingaciu, Laura R.; Ivanova, Oxana; Ohl, Michael; Biehl, Ralf; Richter, Dieter

    2016-01-01

    A flexible linker region between three fragments allows antibodies to adjust their binding sites to an antigen or receptor. Using Neutron Spin Echo Spectroscopy we observed fragment motion on a timescale of 7 ns with motional amplitudes of about 1 nm relative to each other. The mechanistic complexity of the linker region can be described by a spring model with Brownian motion of the fragments in a harmonic potential. Displacements, timescale, friction and force constant of the underlying dynamics are accessed. The force constant exhibits a similar strength to an entropic spring, with friction of the fragment matching the unbound state. The observed fast motions are fluctuations in pre-existing equilibrium configurations. The Brownian motion of domains in a harmonic potential is the appropriate model to examine functional hinge motions dependent on the structural topology and highlights the role of internal forces and friction to function. PMID:27020739

  1. An Impulse Based Substructuring approach for impact analysis and load case simulations

    NASA Astrophysics Data System (ADS)

    Rixen, Daniel J.; van der Valk, Paul L. C.

    2013-12-01

    In the present paper we outline the basic theory of assembling substructures for which the dynamics are described as Impulse Response Functions. The assembly procedure computes the time response of a system by evaluating per substructure the convolution product between the Impulse Response Functions and the applied forces, including the interface forces that are computed to satisfy the interface compatibility. We call this approach the Impulse Based Substructuring method since it transposes to the time domain the Frequency Based Substructuring approach. In the Impulse Based Substructuring technique the Impulse Response Functions of the substructures can be gathered either from experimental tests using a hammer impact or from time-integration of numerical submodels. In this paper the implementation of the method is outlined for the case when the impulse responses of the substructures are computed numerically. A simple bar example is shown in order to illustrate the concept. The Impulse Based Substructuring allows fast evaluation of impact response of a structure when the impulse response of its components is known. It can thus be used to efficiently optimize designs of consumer products by including impact behavior at the early stage of the design, but also for performing substructured simulations of complex structures such as offshore wind turbines.

  2. Unexpected relationships of substructured populations in Chinese Locusta migratoria

    PubMed Central

    Zhang, De-Xing; Yan, Lu-Na; Ji, Ya-Jie; Hewitt, Godfrey M; Huang, Zu-Shi

    2009-01-01

    Background Highly migratory species are usually expected to have minimal population substructure because strong gene flow has the effect of homogenizing genetic variation over geographical populations, counteracting random drift, selection and mutation. The migratory locust Locusta migratoria belongs to a monotypic genus, and is an infamous pest insect with exceptional migratory ability – with dispersal documented over a thousand kilometers. Its distributional area is greater than that of any other locust or grasshopper, occurring in practically all the temperate and tropical regions of the eastern hemisphere. Consequently, minimal population substructuring is expected. However, in marked contrast to its high dispersal ability, three geographical subspecies have been distinguished in China, with more than nine being biologically and morphologically identified in the world. Such subspecies status has been under considerable debate. Results By multilocus microsatellite genotyping analysis, we provide ample genetic evidence for strong population substructure in this highly migratory insect that conforms to geography. More importantly, our genetic data identified an unexpected cryptic subdivision and demonstrated a strong affiliation of the East China locusts to those in Northwest/Northern China. The migratory locusts in China formed three distinct groups, viz. (1) the Tibetan group, comprising locusts from Tibet and nearby West China high mountain regions; this is congruent with the previously recognized Tibetan subspecies, L. m. tibetensis; (2) the South China group, containing locusts from the Hainan islands; this corresponds to the Southeast Asia oriental tropical subspecies L. m. manilensis; (3) the North China group, including locusts from the Northwest and Northern China (the Asiatic subspecies L. m. migratoria), Central China and Eastern China regions. Therefore, the traditional concept on Locusta subspecies status established from Uvarov in 1930s needs to be

  3. Aligning graphs and finding substructures by a cavity approach

    NASA Astrophysics Data System (ADS)

    Bradde, S.; Braunstein, A.; Mahmoudi, H.; Tria, F.; Weigt, M.; Zecchina, R.

    2010-02-01

    We introduce a new distributed algorithm for aligning graphs or finding substructures within a given graph. It is based on the cavity method and is used to study the maximum-clique and the graph-alignment problems in random graphs. The algorithm allows to analyze large graphs and may find applications in fields such as computational biology. As a proof of concept we use our algorithm to align the similarity graphs of two interacting protein families involved in bacterial signal transduction, and to predict actually interacting protein partners between these families.

  4. Simulating and Synthesizing Substructures Using Neural Network and Genetic Algorithms

    NASA Technical Reports Server (NTRS)

    Liu, Youhua; Kapania, Rakesh K.; VanLandingham, Hugh F.

    1997-01-01

    The feasibility of simulating and synthesizing substructures by computational neural network models is illustrated by investigating a statically indeterminate beam, using both a 1-D and a 2-D plane stress modelling. The beam can be decomposed into two cantilevers with free-end loads. By training neural networks to simulate the cantilever responses to different loads, the original beam problem can be solved as a match-up between two subsystems under compatible interface conditions. The genetic algorithms are successfully used to solve the match-up problem. Simulated results are found in good agreement with the analytical or FEM solutions.

  5. Fatigue reassessment for lifetime extension of offshore wind monopile substructures

    NASA Astrophysics Data System (ADS)

    Ziegler, Lisa; Muskulus, Michael

    2016-09-01

    Fatigue reassessment is required to decide about lifetime extension of aging offshore wind farms. This paper presents a methodology to identify important parameters to monitor during the operational phase of offshore wind turbines. An elementary effects method is applied to analyze the global sensitivity of residual fatigue lifetimes to environmental, structural and operational parameters. Therefore, renewed lifetime simulations are performed for a case study which consists of a 5 MW turbine with monopile substructure in 20 m water depth. Results show that corrosion, turbine availability, and turbulence intensity are the most influential parameters. This can vary strongly for other settings (water depth, turbine size, etc.) making case-specific assessments necessary.

  6. The construction of preconditioners for elliptic problems by substructuring, IV

    SciTech Connect

    Bramble, J.H.; Pasciak, J.E.; Schatz, A.H.

    1989-07-01

    We consider the problem of solving the algebraic system of equations which result from the discretization of elliptic boundary value problems defined on three-dimensional Euclidean space. We develop preconditioners for such systems based on substructuring (also known as domain decomposition). The resulting algorithms are well suited to emerging parallel computing architectures. We describe two techniques for developing these preconditioners. A theory for the analysis of the condition number for the resulting preconditioned system is given and the results of supporting numerical experiments are presented.

  7. The construction of preconditioners for elliptic problems by substructuring, IV

    SciTech Connect

    Bramble, J.H.; Pasciak, J.E.; Schatz, A.H.

    1987-06-01

    We consider the problem of solving the algebraic system of equations which result from the discretization of elliptic boundary value problems defined on three dimensional Euclidean space. We develop preconditioners for such systems based on substructuring (also known as domain decomposition). The resulting algorithms are well suited to emerging parallel computing architectures. We describe two techniques for developing these precondictioners. A theory for the analysis of the condition number for the resulting preconditioned system is given and the results of supporting numerical experiments are presented. 16 refs., 2 tabs.

  8. Hierarchically Parallelized Constrained Nonlinear Solvers with Automated Substructuring

    NASA Technical Reports Server (NTRS)

    Padovan, Joe; Kwang, Abel

    1994-01-01

    This paper develops a parallelizable multilevel multiple constrained nonlinear equation solver. The substructuring process is automated to yield appropriately balanced partitioning of each succeeding level. Due to the generality of the procedure,_sequential, as well as partially and fully parallel environments can be handled. This includes both single and multiprocessor assignment per individual partition. Several benchmark examples are presented. These illustrate the robustness of the procedure as well as its capability to yield significant reductions in memory utilization and calculational effort due both to updating and inversion.

  9. Convergence of a Substructuring Method with LaGrange Multipliers

    NASA Technical Reports Server (NTRS)

    Mandel, Jan; Tezaur, Radek

    1996-01-01

    We analyze the convergence of a substructuring iterative method with Lagrange multipliers, proposed recently by Farhat and Roux. The method decomposes finite element discretization of an elliptic boundary value problem into Neumann problems on the subdomains and a coarse problem for the subdomain nullspace components. For linear conforming elements and preconditioning by the Dirichlet problems on the subdomains, we prove the asymptotic bound on the condition number C(1 + log(H/h))(sup gamma), gamma = 2 or 3, where h is the characteristic element size and H is the subdomain size.

  10. Probing linker design in citric acid-ciprofloxacin conjugates.

    PubMed

    Milner, Stephen J; Snelling, Anna M; Kerr, Kevin G; Abd-El-Aziz, Ahmad; Thomas, Gavin H; Hubbard, Roderick E; Routledge, Anne; Duhme-Klair, Anne-Kathrin

    2014-08-15

    A series of structurally related citric acid-ciprofloxacin conjugates was synthesised to investigate the influence of the linker between citric acid and ciprofloxacin on antibacterial activities. Minimum inhibitory concentrations (MICs) were determined against a panel of reference strains and clinical isolates of bacteria associated with infection in humans and correlated with the DNA gyrase inhibitory activity. The observed trend was rationalised by computational modelling.

  11. Engineering Peptide Linkers for scFv Immunosensors

    PubMed Central

    Shen, Zhihong; Yan, Heping; Zhang, Ying; Mernaugh, Raymond L.; Zeng, Xiangqun

    2008-01-01

    Using A10B single-chain fragment variable (scFv) as a model system, we demonstrated that the flexibility of scFv linker engineering can be combined with the inherent quick and adaptable characters of surface coupling chemistry (e.g., electrostatic, hydrogen bonding, or covalent attachment) to attach scFv to preformed functionalized self-assembled monolayers (SAMs). Six arginines, which were separated by glycine or serine as spacer, were incorporated in the peptide linker to form a 15-mer peptide linker (RGRGRGRGRSRGGGS). The polycationic arginine peptide was engineered into the A10B scFv-RG3 to favor its adsorption at anionic charged template surface (11-mercaptoundecanoic acid (MUA) and poly(sodium 4-styrenesulfonate (PSS))). This new approach was compared with the other engineered scFv constructs. Our results demonstrated that the anionic charged SAM template facilitated the oriented immobilization of scFvs on the SAM template surface as well as reduced the possibility of protein denaturation when directly immobilized on the solid surface. A 42-fold improvement of detection limits using MUA/A10B scFv-RG3 (less than 0.2 nM experimentally determined) was achieved compared to A10B Fab antibody and a 5-fold improvement was observed compared to A10B scFv that was engineered with a cysteine in the linker sequence. Using protein A-coated gold nanoparticles, a picomolar experimental detection limit was achieved. With 20 amino acids to choose from, engineered recombinant scFv in combination with SAM technology and nanoparticle mass amplification provide an emerging strategy for the development of highly sensitive and specific scFv immunosensors. PMID:18290668

  12. Click and release: fluoride cleavable linker for mild bioorthogonal separation.

    PubMed

    Schneider, Elia M; Zeltner, Martin; Zlateski, Vladimir; Grass, Robert N; Stark, Wendelin J

    2016-01-18

    Herein, we present a water dispersable, magnetic nanoparticle supported "click and release" system. The cleavable linker has been synthesized by using a strain-promoted copper-free "click" reagent to establish the specific link and a fluoride cleavable silane moiety for mild cleavage. Small organic molecules, azide-bearing dyes and functionalized enzymes have been bound to the magnetic particle and released in a bioorthogonal way.

  13. Modular Degradable Hydrogels Based on Thiol-Reactive Oxanorbornadiene Linkers

    PubMed Central

    2016-01-01

    Oxanorbornadiene dicarboxylate (OND) reagents are potent Michael acceptors, the adducts of which undergo fragmentation by retro-Diels–Alder reaction at rates that vary with the substitution pattern on the OND moiety. Rapid conjugate addition between thiol-terminated tetravalent PEG and multivalent ONDs yielded self-supporting hydrogels within 1 min at physiological temperature and pH. Erosion of representative hydrogel formulations occurred with predictable and pH-independent rates on the order of minutes to weeks. These materials could be made non-degradable by epoxidation of the OND linkers without slowing gelation. Hydrogels prepared with OND linkers of equal valence had comparable physical properties, as determined by equilibrium swelling behavior, indicating similar internal network structure. Diffusion and release of entrained cargo varied with both the rate of degradation of PEG-OND hydrogels and the hydrodynamic radius of the entrained species. These results highlight the utility of OND linkers in the preparation of degradable network materials with potential applications in sustained release. PMID:25871459

  14. Internucleotide protein linkers in Ehrlich ascites cell DNA.

    PubMed

    Werner, D; Krauth, W; Hershey, H V

    1980-07-29

    DNA from Ehrlich ascites tumor cells is nicked or gapped by a reaction which is induced by proteases such as autodigested pronase, proteinase K, trypsin, chymotrypsin and subtilisin. The cleavage of the protease-sensitive sites is inhibited by protease inhibitors. The nicks or gaps induced by proteases can be demonstrated by nuclease S1 sensitivity of native DNA and by a change of the sedimentation rate of alkali-denatured DNA. The limit size of denatured DNA released after optimal protease treatment is 8.5 x 10(6) daltons (27 kilo bases). The molecular weight of the native DNA pieces released after nuclease S1 degradation of DNA containing the protease-induced nicks or gaps is in the same order indicating that the protease-sensitive sites are alternatively arranged on the opposite DNA strands at an average distance of 13.5 kilo base pairs. Since the protease-induced nicks or gaps in phosphatase-treated DNA are not attacked by Escherichia coli polymerase I, one or both ends liberated by the protease treatment must be blocked by a material other than phosphate groups. The results are most compatible with peptide/protein linkers joining adjacent single-strand DNA subunits. Alternative explanations such as alkali-stable RNA linkers, protein-protected RNA linkers, site-specific nuclease contaminations in the protease preparations or cellular nucleases activated by the protease treatment are eliminated by the results presented in this paper.

  15. Alternating zinc fingers in the human male associated protein ZFY: 2D NMR structure of an even finger and implications for jumping-linker DNA recognition

    SciTech Connect

    Kochoyan, M.; Havel, T.F.; Dahl, C.E. ); Nguyen, D.T.; Keutmann, H.T. ); Weiss, M.A. Massachusetts General Hospital, Boston )

    1991-04-09

    ZFY, a sex-related Zn-finger protein encoded by the human Y chromosome, is distinguished from the general class of Zn-finger proteins by the presence of a two-finger repeat. Whereas odd-numbered domains and linkers fit a general consensus, even-numbered domains and linkers exhibit systematic differences. Because this alternation may have fundamental implications for the mechanism of protein-DNA recognition, the authors have undertaken biochemical and structural studies of fragments of ZFY. They describe here the solution structure of a representative nonconsensus (even-numbered) Zn finger based on 2D NMR studies of a 30-residue peptide. Structural modeling by distance geometry and simulated annealing (DG/SA) demonstrates that this peptide folds as a miniglobular domain containing a C-terminal {beta}-hairpin and N-terminal {alpha}-helix ({beta}{beta}{alpha} motif). These features are similar to (but not identical with) those previously described in consensus-type Zn fingers (derived from ADR1 and Xfin); the similarities suggest that even and odd ZFY domains bind DNA by a common mechanism. A model of the protein-DNA complex (designated the jumping-linker model) is presented and discussed in terms of the ZFY two-finger repeat. In this model every other linker is proposed to cross the minor groove by means of a putative finger/linker submotif HX{sub 4}HX{sub 3}-hydrophobic residue-X{sub 3}.

  16. Calcium gluconate as cross-linker improves survival and shelf life of encapsulated and dried Metarhizium brunneum and Saccharomyces cerevisiae for the application as biological control agents.

    PubMed

    Humbert, Pascal; Przyklenk, Michael; Vemmer, Marina; Patel, Anant V

    2017-02-01

    Calcium chloride (CC) is the most common cross-linker for the encapsulation of biocontrol microorganisms in alginate beads. The aim of this study was to evaluate if calcium gluconate (CG) can replace CC as cross-linker and at the same time improve viability after drying and rehydration, hygroscopic properties, shelf life and nutrient supply. Hence, the biocontrol fungi Metarhizium brunneum and Saccharomyces cerevisiae were encapsulated in Ca-alginate beads supplemented with starch. Beads were dried and maximum survival was found in beads cross-linked with CG. Beads prepared with CG showed lower hygroscopic properties, but a higher shelf life for encapsulated fungi. Moreover, we demonstrated that gluconate has a nutritive effect on encapsulated fungi, leading to increased mycelium growth of M. brunneum and to enhanced CO2 release from beads containing Saccharomyces cerevisiae. The application of CG as cross-linker will pave the way towards increasing drying survival and shelf life of various, especially drying-sensitive microbes.

  17. Latent Oxidative Polymerization of Catecholamines as Potential Cross-linkers for Biocompatible and Multifunctional Biopolymer Scaffolds.

    PubMed

    Dhand, Chetna; Barathi, Veluchamy Amutha; Ong, Seow Theng; Venkatesh, Mayandi; Harini, Sriram; Dwivedi, Neeraj; Goh, Eunice Tze Leng; Nandhakumar, Muruganantham; Venugopal, Jayarama Reddy; Diaz, Silvia Marrero; Fazil, Mobashar Hussain Urf Turabe; Loh, Xian Jun; Ping, Liu Shou; Beuerman, Roger W; Verma, Navin Kumar; Ramakrishna, Seeram; Lakshminarayanan, Rajamani

    2016-11-30

    Electrospinning of naturally occurring biopolymers for biological applications requires postspinning cross-linking for endurance in protease-rich microenvironments and prevention of rapid dissolution. The most commonly used cross-linkers often generate cytotoxic byproducts, which necessitate high concentrations or time-consuming procedures. Herein, we report the addition of "safe" catecholamine cross-linkers to collagen or gelatin dope solutions followed by electrospinning yielded junction-containing nanofibrous mats. Subsequent in situ oxidative polymerization of the catecholamines increased the density of soldered junctions and maintained the porous nanofiber architecture. This protocol imparted photoluminescence to the biopolymers, a smooth noncytotoxic coating, and good mechanical/structural stability in aqueous solutions. The utility of our approach was demonstrated by the preparation of durable antimicrobial wound dressings and mineralized osteoconductive scaffolds via peptide antibiotics and calcium chloride (CaCl2) incorporation into the dope solutions. The mineralized composite mats consist of amorphous calcium carbonate that enhanced the osteoblasts cell proliferation, differentiation, and expression of important osteogenic marker proteins. In proof-of-concept experiments, antibiotic-loaded mats displayed superior antimicrobial properties relative to silver (Ag)-based dressings, and accelerated wound healing in a porcine deep dermal burn injury model.

  18. Linker polypeptides of the phycobilisome from the cyanobacterium Mastigocladus laminosus. I. Isolation and characterization of phycobiliprotein-linker-polypeptide complexes.

    PubMed

    Füglistaller, P; Suter, F; Zuber, H

    1986-07-01

    Phycobilisomes from the cyanobacterium Mastigocladus laminosus cultured in white and red light were isolated and compared with respect to the phycoerythrocyanin (PEC) and linker polypeptide contents. It was verified that the production of PEC is induced by low light intensities. A PEC complex, (alpha PEC beta PEC)6LR34.5,PEC, and a phycocyanin (PC) complex, (alpha PC beta PC)6LR34.5,PC, were isolated from phycobilisomes by Cellex-D anion exchange chromatography and sucrose density gradient centrifugation. The absorption and fluorescence emission maxima of the PEC complex are at 575 and 620 nm and those of the PC complex are at 631 and 647 nm, respectively. The extinction coefficients of the two complexes were determined. From different experiments it was concluded that PEC is present as a hexameric complex, (alpha PEC beta PEC)6LR34.5,PEC, in the phycobilisome. The two linker polypeptides LR34.5,PEC and LR34.5,PC were isolated from their phycobiliprotein complexes by gel filtration on Bio-Gel P-100 in 50% formic acid. A 5-kDa terminal segment of both linker polypeptides was found to influence the hexamer formation of the phycobiliproteins. The same segments have been described to be responsible for the hexamer-hexamer linkage (Yu, M.-H. & Glazer, A.N. (1982) J. Biol. Chem. 257, 3429-3433). A 8.9-kDa linker polypeptide, LR(C)8.9, was isolated from a PEC fraction of the Cellex-D column by Bio-Gel P-100 gel filtration in 50% formic acid. Localisation of this protein within the phycobilisome was attempted. Its most probable function is to terminate the phycobilisomal rods at the end distal to the allophycocyanin core.

  19. Quantum-chemical foundations of the topological substructural molecular design.

    PubMed

    Estrada, Ernesto

    2008-06-12

    The topological substructural molecular design (TOPS-MODE) approach is formulated as a tight-binding quantum-chemical method. The approach is based on certain postulates that permit to express any molecular property as a function of the spectral moments of certain types of molecular and environment-dependent energies. We use several empirical potentials to account for these intrinsic and external molecular energies. We prove that any molecular property expressed in terms of a quantitative structure-property and structure-activity relationships (QSPR/QSAR) model developed by using the TOPS-MODE method can be expressed as a bond additivity function. In addition, such a property can also be expressed as a substructural cluster expansion function. The conditions for such bond contributions being transferable are also analyzed here. Several new statistical-mechanical electronic functions are introduced as well as a bond-bond thermal Green's function or a propagator accounting for the electronic hopping between pairs of bonds. All these new concepts are applied to the development and application of a new QSAR model for describing the toxicity of polyhalogenated-dibenzo-1,4-dioxins. The QSAR model obtained displays a significant robustness and predictability. It permits an easy structural interpretation of the structure-activity relationship in terms of bond additivity functions, which display some resemblances with other theoretical parameters obtained from first principle quantum-chemical methods.

  20. Population genetic analysis and sub-structuring in Babesia bovis.

    PubMed

    Simuunza, Martin; Bilgic, Huseyin; Karagenc, Tulin; Syakalima, Michelo; Shiels, Brian; Tait, Andy; Weir, William

    2011-06-01

    The tick-borne protozoan parasite, Babesia bovis is one of the causes of bovine babesiosis, an economically important disease of cattle in tropical and sub-tropical countries. Using the recently published genome sequence of the parasite, we developed a panel of eight mini- and micro-satellite markers and used these to investigate the role of genetic exchange in the population structure and diversity of the parasite using isolates from Zambia and Turkey. This population genetic analysis showed that genetic exchange occurs and that there are high levels of genetic diversity, with geographical sub-structuring quantified using Wright's F Index. Linkage disequilibrium was observed when isolates from both countries were treated as one population, but when isolates from Zambia were analysed separately linkage equilibrium was observed. The Turkish isolates were sub-structured, containing two genetically distinct sub-groups, both of which appeared to be in linkage equilibrium. The results of the Zambian study suggest that a sub-set of the parasite population is responsible for the westward spread of babesiosis into the previously disease-free central region of the country. The Zambian isolates had a significantly higher number of genotypes per sample than those from Turkey and age was found to be a significant predictor of the multiplicity of infection. The high levels of diversity seen in the Zambian and Turkish B. bovis populations have implications in the development of subunit vaccines against the disease and the spread of drug resistance.

  1. Construction of a linker library with widely controllable flexibility for fusion protein design.

    PubMed

    Li, Gang; Huang, Ziliang; Zhang, Chong; Dong, Bo-Jun; Guo, Ruo-Hai; Yue, Hong-Wei; Yan, Li-Tang; Xing, Xin-Hui

    2016-01-01

    Flexibility or rigidity of the linker between two fused proteins is an important parameter that affects the function of fusion proteins. In this study, we constructed a linker library with five elementary units based on the combination of the flexible (GGGGS) and the rigid (EAAAK) units. Molecular dynamics (MD) simulation showed that more rigid units in the linkers lead to more helical conformation and hydrogen bonds, and less distance fluctuation between the N- and C-termini of the linker. The diversity of linker flexibility of the linker library was then studied by fluorescence resonance energy transfer (FRET) of cyan fluorescent protein (CFP)-yellow fluorescent protein (YFP) fusion proteins, which showed that there is a wide range of distribution of the FRET efficiency. Dissipative particle dynamics (DPD) simulation of CFP-YFP with different linkers also gave identical results with that of FRET efficiency analysis, and we further found that the combination manner of the linker peptide had a remarkable effect on the orientation of CFP and YFP domains. Our studies demonstrated that the construction of the linker library with the widely controllable flexibility could provide appropriate linkers with the desirable characteristics to engineer the fusion proteins with the expected functions.

  2. A Comparison of Reduced Order Modeling Techniques Used in Dynamic Substructuring [PowerPoint

    SciTech Connect

    Roettgen, Dan; Seeger, Benjamin; Tai, Wei Che; Baek, Seunghun; Dossogne, Tilan; Allen, Matthew S; Kuether, Robert J.; Brake, Matthew Robert; Mayes, Randall L.

    2016-01-01

    Experimental dynamic substructuring is a means whereby a mathematical model for a substructure can be obtained experimentally and then coupled to a model for the rest of the assembly to predict the response. Recently, various methods have been proposed that use a transmission simulator to overcome sensitivity to measurement errors and to exercise the interface between the substructures; including the Craig-Bampton, Dual Craig-Bampton, and Craig-Mayes methods. This work compares the advantages and disadvantages of these reduced order modeling strategies for two dynamic substructuring problems. The methods are first used on an analytical beam model to validate the methodologies. Then they are used to obtain an experimental model for structure consisting of a cylinder with several components inside connected to the outside case by foam with uncertain properties. This represents an exceedingly difficult structure to model and so experimental substructuring could be an attractive way to obtain a model of the system.

  3. A Comparison of Reduced Order Modeling Techniques Used in Dynamic Substructuring.

    SciTech Connect

    Roettgen, Dan; Seegar, Ben; Tai, Wei Che; Baek, Seunghun; Dossogne, Tilan; Allen, Matthew; Kuether, Robert J.; Brake, Matthew Robert; Mayes, Randall L.

    2015-10-01

    Experimental dynamic substructuring is a means whereby a mathematical model for a substructure can be obtained experimentally and then coupled to a model for the rest of the assembly to predict the response. Recently, various methods have been proposed that use a transmission simulator to overcome sensitivity to measurement errors and to exercise the interface between the substructures; including the Craig-Bampton, Dual Craig-Bampton, and Craig-Mayes methods. This work compares the advantages and disadvantages of these reduced order modeling strategies for two dynamic substructuring problems. The methods are first used on an analytical beam model to validate the methodologies. Then they are used to obtain an experimental model for structure consisting of a cylinder with several components inside connected to the outside case by foam with uncertain properties. This represents an exceedingly difficult structure to model and so experimental substructuring could be an attractive way to obtain a model of the system.

  4. Nucleosomes, Linker DNA, and Linker Histone form a Unique Structural Motif that Directs the Higher-Order Folding and Compaction of Chromatin

    NASA Astrophysics Data System (ADS)

    Bednar, Jan; Horowitz, Rachel A.; Grigoryev, Sergei A.; Carruthers, Lenny M.; Hansen, Jeffrey C.; Koster, Abraham J.; Woodcock, Christopher L.

    1998-11-01

    The compaction level of arrays of nucleosomes may be understood in terms of the balance between the self-repulsion of DNA (principally linker DNA) and countering factors including the ionic strength and composition of the medium, the highly basic N termini of the core histones, and linker histones. However, the structural principles that come into play during the transition from a loose chain of nucleosomes to a compact 30-nm chromatin fiber have been difficult to establish, and the arrangement of nucleosomes and linker DNA in condensed chromatin fibers has never been fully resolved. Based on images of the solution conformation of native chromatin and fully defined chromatin arrays obtained by electron cryomicroscopy, we report a linker histone-dependent architectural motif beyond the level of the nucleosome core particle that takes the form of a stem-like organization of the entering and exiting linker DNA segments. DNA completes ≈ 1.7 turns on the histone octamer in the presence and absence of linker histone. When linker histone is present, the two linker DNA segments become juxtaposed ≈ 8 nm from the nucleosome center and remain apposed for 3-5 nm before diverging. We propose that this stem motif directs the arrangement of nucleosomes and linker DNA within the chromatin fiber, establishing a unique three-dimensional zigzag folding pattern that is conserved during compaction. Such an arrangement with peripherally arranged nucleosomes and internal linker DNA segments is fully consistent with observations in intact nuclei and also allows dramatic changes in compaction level to occur without a concomitant change in topology.

  5. Functionalization of metallic magnesium with protein layers via linker molecules.

    PubMed

    Killian, Manuela S; Wagener, Victoria; Schmuki, Patrik; Virtanen, Sannakaisa

    2010-07-20

    We present an innovative method to cover pure magnesium with protein monolayers by utilizing the OH termination of the oxide surface and silane coupling chemistry. The protein of interest was albumin. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS) were used to monitor the success of the treatment. The attachment of proteins via linker groups yielded smoother and more homogeneous surfaces than coatings produced by steeping magnesium in protein solution. A positive effect on the corrosion behavior of pure magnesium was also observed.

  6. Solid-phase synthesis of lidocaine and procainamide analogues using backbone amide linker (BAL) anchoring.

    PubMed

    Shannon, Simon K; Peacock, Mandy J; Kates, Steven A; Barany, George

    2003-01-01

    New solid-phase strategies have been developed for the synthesis of lidocaine (1) and procainamide (2) analogues, using backbone amide linker (BAL) anchoring. Both sets were prepared starting from a common resin-bound intermediate, followed by four general steps: (i) attachment of a primary aliphatic or aromatic amine to the solid support via reductive amination (as monitored by a novel test involving reaction of 2,4-dinitrophenylhydrazine with residual aldehyde groups); (ii) acylation of the resultant secondary amine; (iii) displacement of halide with an amine; and (iv) trifluoroacetic acid-mediated release from the support. A manual parallel strategy was followed to provide 60 novel compounds, of which two dozen have not been previously described. In most cases, initial crude purities were >80%, and overall isolated yields were in the 40-88% range.

  7. Population substructure in Cache County, Utah: the Cache County study

    PubMed Central

    2014-01-01

    Background Population stratification is a key concern for genetic association analyses. In addition, extreme homogeneity of ethnic origins of a population can make it difficult to interpret how genetic associations in that population may translate into other populations. Here we have evaluated the genetic substructure of samples from the Cache County study relative to the HapMap Reference populations and data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Results Our findings show that the Cache County study is similar in ethnic diversity to the self-reported "Whites" in the ADNI sample and less homogenous than the HapMap CEU population. Conclusions We conclude that the Cache County study is genetically representative of the general European American population in the USA and is an appropriate population for conducting broadly applicable genetic studies. PMID:25078123

  8. Substructure In The Scorpius-Centaurus OB Association

    NASA Astrophysics Data System (ADS)

    Pecaut, Mark J.; Mamajek, Eric E.

    2016-07-01

    OB associations are remnants of star formation on a large scale, producing everything from O- and B-type stars, down to the lowest mass brown dwarfs. OB associations represent the typical mode of star formation in the Galaxy. But is this process monolithic? We present the results of a survey for new, solar mass (0.7 - 1.3 Msun) members of Sco-Cen, the nearest OB Association to the Sun. We identify 150 new members and place the known B/A/F/G/K/M-type members on the Hertzsprung-Russell diagram. From these data, we construct an age map of Sco-Cen, occupying approximately 2,000 square degrees on the sky. These results indicate there is substantial substructure in Sco-Cen, and present the possibility that star formation on the largest scales can be considered a collection of many individual, small-scale star formation events along a giant molecular cloud.

  9. Probing Galaxy Clusters and Substructures using Gravitational Lensing

    NASA Astrophysics Data System (ADS)

    Choi, Miyoung; Nguyen, Hoang; King, Lindsay; Lee, Brandyn E.; McCarthy, Ian

    2017-01-01

    Gravitational lensing is one of the most promising methods of analyzing massive astronomical objects such as galaxy clusters. The weak gravitational lensing signal, which is called shear, is a measurement of the weak distortion of background galaxies in the linear regime of the lensing field. Shear analysis effectively estimates the main properties of galaxy clusters such as the mass and scale of the lensing system. The second order gravitational lensing signal, flexion, is dominant in the non-linear regime of the lensing field that bridges the strong and weak lensing regimes. It has also recently arisen as a robust method to detect substructures in galaxy clusters due to its sensitivity to the gradient of convergence and shear field. In this poster we propose that combining the shear and flexion analysis can give more information about the detailed structure of the lensing system.

  10. Construction of preconditioners for elliptic problems by substructuring. I

    SciTech Connect

    Bramble, J.H.; Pasciak, J.E.; Schatz, A.H.

    1986-07-01

    We consider the problem of solving the algebraic system of equations which arise from the discretization of symmetric elliptic boundary value problems via finite element methods. A new class of preconditioners for the discrete system is developed based on substructuring (also known as domain decomposition). The resulting preconditioned algorithms are well suited to emerging parallel computing architectures. The proposed methods are applicable to problems on general domains involving differential operators with rather general coefficients. A basic theory for the analysis of the condition number of the preconditioned system (which determines the iterative convergence rate of the algorithm) is given. Techniques for applying the theory and algorithms to problems with irregular geometry are discussed and the results of extensive numerical experiments are reported.

  11. Dynamics of 10 clusters of galaxies with substructures

    SciTech Connect

    Lakhchaura, Kiran; Singh, K. P.

    2014-06-01

    We present a detailed Chandra study of a sample of 10 clusters of galaxies selected based on the presence of substructures in their optical images. The X-ray surface brightness maps of most of these clusters show anisotropic morphologies, especially in the central regions. A total of 22 well resolved significantly bright X-ray peaks (corresponding with high-density regions) are seen in the central parts (within r{sub c} /2) of the clusters. Multiple peaks are seen in central parts of six clusters. We found 11 peaks to have optical counterparts (10 coinciding with the brightest cluster galaxies of the 10 clusters and 1 coinciding with the second brightest galaxy in A539). For most of the clusters, the optical substructures detected in the previous studies are found to be outside the field of view of Chandra. In the spectroscopically produced two-dimensional temperature maps, significantly lower temperatures are seen at the locations of three peaks (two in A539 and one in A376). The centers of five clusters in our sample also host regions of higher temperature compared to the ambient medium, indicating the presence of galaxy scale mergers. The X-ray luminosity, gas mass, and central cooling time estimates for all the clusters are presented. The radial X-ray surface-brightness profiles of all but one of the clusters are found to be best-fitted with a double-β model, pointing toward the presence of double-phased central gas due to cool cores. The cooling time estimates of all the clusters, however, indicate that none of them hosts a strong cool core, although the possibility of weak cool cores cannot be ruled out.

  12. Nucleolonema as a fundamental substructure of the nucleolus.

    PubMed

    Sato, Seiichi; Yano, Hiroyuki; Makimoto, Yuji; Kaneta, Tsuyoshi; Sato, Yasushi

    2005-04-01

    The nucleolus is the most obvious structure in the eukaryotic nucleus. It is known to be a ribosome-producing apparatus where ribosomal (r) DNA is transcribed and the primary rRNA transcripts are processed to produce three of the four rRNA species. Electron microscopy has shown that the nucleolus consists of three major components, a dense fibrillar component (DFC), a granular component (GC) and a fibrillar center (FC). The DFC and FCs are integrated into a fundamental nucleolar substructure called the nucleolonema. The DFC corresponds to the matrix of the nucleolonema, and the FC is an electron microscopic counterpart of argyrophobic lacunae localized in the nucleolonema. The spherical FCs are intermittently arranged along the length of the nucleolonema in actively growing cells but are fused with each other to form tubular FCs when rDNA transcription is hampered. The RNase-gold complex does not bind to the FC but to the DFC and the GC, suggesting that rDNA transcription does not occur in the FC although both fluorescence in situ hybridization (FISH) and electron microscopic in situ hybridization reveal that the rDNA is specifically localized in the FCs. Immunogold-labeling after bromo-UTP (BrUTP) incorporation shows that rDNA transcription takes place in the boundary region between the FC and the DFC, and primary rRNA transcripts are expected to be processed outward within the DFC. Data have accumulated suggesting that the nucleolonema is a fundamental substructure of the nucleolus, and its skeleton is the tandem arrangement of the FCs, which are resting harbors or storages of rDNA. This paper proposes that the transversal structural organization of the nucleolonema is centrifugally built up by several structural and functional domains: condensed and/or loosened rDNA, rDNA transcription zone, and transcript processing and ribosome assembly zones.

  13. Open and closed: the roles of linker histones in plants and animals.

    PubMed

    Over, Ryan S; Michaels, Scott D

    2014-03-01

    Histones package DNA in all eukaryotes and play key roles in regulating gene expression. Approximately 150 base pairs of DNA wraps around an octamer of core histones to form the nucleosome, the basic unit of chromatin. Linker histones compact chromatin further by binding to and neutralizing the charge of the DNA between nucleosomes. It is well established that chromatin packing is regulated by a complex pattern of posttranslational modifications (PTMs) to core histones, but linker histone function is less well understood. In this review, we describe the current understanding of the many roles that linker histones play in cellular processes, including gene regulation, cell division, and development, while putting the linker histone in the context of other nuclear proteins. Although intriguing roles for plant linker histones are beginning to emerge, much of our current understanding comes from work in animal systems. Many unanswered questions remain and additional work is required to fully elucidate the complex processes mediated by linker histones in plants.

  14. Germline-specific H1 variants: the "sexy" linker histones.

    PubMed

    Pérez-Montero, Salvador; Carbonell, Albert; Azorín, Fernando

    2016-03-01

    The eukaryotic genome is packed into chromatin, a nucleoprotein complex mainly formed by the interaction of DNA with the abundant basic histone proteins. The fundamental structural and functional subunit of chromatin is the nucleosome core particle, which is composed by 146 bp of DNA wrapped around an octameric protein complex formed by two copies of each core histone H2A, H2B, H3, and H4. In addition, although not an intrinsic component of the nucleosome core particle, linker histone H1 directly interacts with it in a monomeric form. Histone H1 binds nucleosomes near the exit/entry sites of linker DNA, determines nucleosome repeat length and stabilizes higher-order organization of nucleosomes into the ∼30 nm chromatin fiber. In comparison to core histones, histone H1 is less well conserved through evolution. Furthermore, histone H1 composition in metazoans is generally complex with most species containing multiple variants that play redundant as well as specific functions. In this regard, a characteristic feature is the presence of specific H1 variants that replace somatic H1s in the germline and during early embryogenesis. In this review, we summarize our current knowledge about their structural and functional properties.

  15. A Traceless Cross-linker for Photo-Cleavable Bioconjugation

    PubMed Central

    Wang, Rong; Yan, Funing; Qiu, Dengli; Jeong, Jae-Sun; Jin, Qiaoling; Kim, Tae-Young; Chen, Liaohai

    2012-01-01

    Photo-responsive bioconjugation empowers the development of novel methods for drug discovery, disease diagnosis, and high-throughput screening, among the others. In this paper, we report on the characteristics of a traceless photo-cleavable cross-linker, di 6-(3-succinimidyl carbonyloxymethyl-4-nitro-phenoxy)-hexanoic acid disulfide diethanol ester (SCNE). The traceless feature and the biocompatibility of this photo-cleavable cross-linking reagent were corroborated. Consequently, we demonstrated its application in reversible phage particle immobilization that could provide a platform for direct single phage screening. We also applied it in protein-photoprinting, where SCNE acts as a “photo-eraser” to remove the cross-linked protein molecules at a desired region in a simple, clean and light-controllable fashion. We further demonstrated the two-tier atomic force microscopic (AFM) method that uses SCNE to carry out two subsequent AFM tasks in situ. The approach allows guided protein delivery and subsequent high-resolution imaging at the same local area, thus opens up the possibility of monitoring protein functions in live cells. The results imply that SCNE is a versatile cross-linker that can be used for a wide range of applications where photo-cleavage ensures clean and remote-controllable release of biological molecules from a substrate. PMID:22432929

  16. Nonlinear signal-based control with an error feedback action for nonlinear substructuring control

    NASA Astrophysics Data System (ADS)

    Enokida, Ryuta; Kajiwara, Koichi

    2017-01-01

    A nonlinear signal-based control (NSBC) method utilises the 'nonlinear signal' that is obtained from the outputs of a controlled system and its linear model under the same input signal. Although this method has been examined in numerical simulations of nonlinear systems, its application in physical experiments has not been studied. In this paper, we study an application of NSBC in physical experiments and incorporate an error feedback action into the method to minimise the error and enhance the feasibility in practice. Focusing on NSBC in substructure testing methods, we propose nonlinear substructuring control (NLSC), that is a more general form of linear substructuring control (LSC) developed for dynamical substructured systems. In this study, we experimentally and numerically verified the proposed NLSC via substructuring tests on a rubber bearing used in base-isolated structures. In the examinations, NLSC succeeded in gaining accurate results despite significant nonlinear hysteresis and unknown parameters in the substructures. The nonlinear signal feedback action in NLSC was found to be notably effective in minimising the error caused by nonlinearity or unknown properties in the controlled system. In addition, the error feedback action in NLSC was found to be essential for maintaining stability. A stability analysis based on the Nyquist criterion, which is used particularly for linear systems, was also found to be efficient for predicting the instability conditions of substructuring tests with NLSC and useful for the error feedback controller design.

  17. Association of systemic lupus erythematosus clinical features with European population genetic substructure.

    PubMed

    Alonso-Perez, Elisa; Suarez-Gestal, Marian; Calaza, Manuel; Witte, Torsten; Papasteriades, Chryssa; Marchini, Maurizio; Migliaresi, Sergio; Kovacs, Attila; Ordi-Ros, Josep; Bijl, Marc; Santos, Maria Jose; Ruzickova, Sarka; Pullmann, Rudolf; Carreira, Patricia; Skopouli, Fotini N; D'Alfonso, Sandra; Sebastiani, Gian Domenico; Suarez, Ana; Blanco, Francisco J; Gomez-Reino, Juan J; Gonzalez, Antonio

    2011-01-01

    Systemic Lupus Erythematosus (SLE) is an autoimmune disease with a very varied spectrum of clinical manifestations that could be partly determined by genetic factors. We aimed to determine the relationship between prevalence of 11 clinical features and age of disease onset with European population genetic substructure. Data from 1413 patients of European ancestry recruited in nine countries was tested for association with genotypes of top ancestry informative markers. This analysis was done with logistic regression between phenotypes and genotypes or principal components extracted from them. We used a genetic additive model and adjusted for gender and disease duration. Three clinical features showed association with ancestry informative markers: autoantibody production defined as immunologic disorder (P = 6.8×10(-4)), oral ulcers (P = 6.9×10(-4)) and photosensitivity (P = 0.002). Immunologic disorder was associated with genotypes more common in Southern European ancestries, whereas the opposite trend was observed for photosensitivity. Oral ulcers were specifically more common in patients of Spanish and Portuguese self-reported ancestry. These results should be taken into account in future research and suggest new hypotheses and possible underlying mechanisms to be investigated. A first hypothesis linking photosensitivity with variation in skin pigmentation is suggested.

  18. Small-scale Substructure in Dark Matter Haloes: Where Does Galaxy Formation Come to an End?

    NASA Astrophysics Data System (ADS)

    Taylor, J. E.; Silk, J.; Babul, A.

    2004-07-01

    Models of structure formation based on cold dark matter predict that most of the small dark matter haloes that first formed at high redshift would have merged into larger systems by the present epoch. Substructure in present-day haloes preserves the remains of these ancient systems, providing the only direct information we may ever have about the low-mass end of the power spectrum. We describe some recent attempts to model halo substructure down to very small masses, using a semi-analytic model of halo formation. We make a preliminary comparison between the model predictions, observations of substructure in lensed systems, and the properties of local satellite galaxies.

  19. Effect of load eccentricity and substructure deformation on ultimate strength of shuttle orbiter thermal protection system

    NASA Technical Reports Server (NTRS)

    Sawyer, J. W.

    1981-01-01

    The effect of load eccentricity and substructure deformation on the ultimate strength and stress displacement properties of the shuttle orbiter thermal protection system (TPS) was determined. The LI-900 Reusable Surface Insulation (RSI) tiles mounted on the .41 cm thick Strain Isolator Pad (SIP) were investigated. Substructure deformations reduce the ultimate strength of the SIP/tile TPS and increase the scatter in the ultimate strength data. Substructure deformations that occur unsymmetric to the tile can cause the tile to rotate when subjected to a uniform applied load. Load eccentricity reduces SIP/tile TPS ultimate strength and causes tile rotation.

  20. Evolutionary correlation between linker histones and microtubular structures.

    PubMed

    Kaczanowski, S; Jerzmanowski, A

    2001-07-01

    Histones of the H1 group (linker histones) are abundant components of chromatin in eukaryotes, occurring on average at one molecule per nucleosome. The recent reports on the lack of a clear phenotypic effect of knock-out mutations as well as overexpression of histone H1 genes in different organisms have seriously undermined the long-held view that linker histones are essential for the basic functions of eukaryotic cells. In an attempt to resolve the paradox of an abundant conserved protein without a clear function, we re-examined the molecular and phylogenetic data on linker histones to see if they could reveal any correlation between the features of H1 and the functional or morphological characteristics of cells or organisms. Because of an earlier demonstration that in sea urchin the chromatin-type histone H1 is also found in the flagellar microtubules (Multigner et al. 1992), we focused on the correlation between the features of H1 and those of microtubular structures. A phylogenetic tree based on multiple alignment of over 100 available HI sequences suggests that the first divergence of the globular domain of H1 (GH1) resulted in branching into separate types characteristic for plants/Dictyostelium and for animals/ascomycetes, respectively. The GH1s of these two types differ by a short region (usually 5 amino acids) placed at a specific location within the C-terminal wing subdomain of GH1. Evolutionary analysis of the diversification of H1 mRNA into cell-cycle-dependent (polyA-) and independent (polyA+) forms showed a mosaic occurrence of these two forms in plants and animals, despite the fact that the H1 proteins of plants and animals belong to two well-distinguished groups. However, among organisms from both animal and plant kingdom, only those with H1 mRNA of a polyA- type have flagellated gametes. This correlation as well as the demonstration that in Volvox carteri the accumulation of polyA- mRNA of H1 occurs concurrently with the production of new flagella

  1. O-glycosylation of glycine-serine linkers in recombinant Fc-fusion proteins: attachment of glycosaminoglycans and other intermediates with phosphorylation at the xylose sugar subunit.

    PubMed

    Spahr, Chris; Shi, Stone D-H; Lu, Hsieng S

    2014-01-01

    A xylose-based glycosaminoglycan (GAG) core was recently identified at a Ser residue in the linker sequence of a recombinant Fc fusion protein. The linker sequence, G-S-G-G-G-G, and an upstream acidic residue were serving as a substrate for O-xylosyltransferase, resulting in a major glycan composed of Xyl-Gal-Gal-GlcA and other minor intermediates. In this paper, a portion of an unrelated protein was fused to the C-terminus of an IgG Fc domain using the common (G4S) 4 linker repeat. This linker resulted in a heterogenous population of xylose-based glycans all containing at least a core Xyl. Commonly observed glycan structures include GAG-related di-, tri-, tetra-, and penta-saccharides (e.g., Xyl-Gal, Xyl-Gal-Gal, Xyl-Gal-Gal-GlcA, and Xyl-Gal-Gal-GlcA-HexNAc), as well as Xyl-Gal-Neu5Ac. Following alkaline phosphatase or sialidase treatment combined with CID fragmentation, low-level glycans with a mass addition of 79.9 Da were confirmed to be a result of phosphorylated xylose. A minute quantity of phosphorylated GAG pentasaccharides may also be sulfated (also 79.9 Da), possibly at the HexNAc moiety due to non-reactivity to alkaline phosphatase. The xylose moiety may be randomly incorporated in one of the three G-S-G sequence motifs; and the linker peptide shows evidence for multiple additions of xylose at very low levels.

  2. Structure based design of protein linkers for zinc finger nuclease.

    PubMed

    Anand, Priya; Schug, Alexander; Wenzel, Wolfgang

    2013-10-01

    Zinc finger nucleases are a promising tool to edit DNA in many biological applications, in particular for gene knockout. Despite many efforts the number of genes that can be effectively targeted with ZFNs remains severely limited, as available constructs cannot address arbitrary gene sequences. Here, we develop a novel concept to significantly enhance the number of DNA sequences that can be targeted by ZFN. Using an efficient computational model, we provide an extensive library of possible linker molecules between individual zinc finger motifs in the construct that can skip up to 10 base pairs between adjacent zinc finger recognition sites in the DNA sequence, which increases the number of genes that can be efficiently targeted by more than an order of magnitude.

  3. New Structural-Dynamics Module for Offshore Multimember Substructures within the Wind Turbine Computer-Aided Engineering Tool FAST: Preprint

    SciTech Connect

    Song, H.; Damiani, R.; Robertson, A.; Jonkman, J.

    2013-08-01

    FAST, developed by the National Renewable Energy Laboratory (NREL), is a computer-aided engineering (CAE) tool for aero-hydro-servo-elastic analysis of land-based and offshore wind turbines. This paper discusses recent upgrades made to FAST to enable loads simulations of offshore wind turbines with fixed-bottom, multimember support structures (e.g., jackets and tripods, which are commonly used in transitional-depth waters). The main theory and strategies for the implementation of the multimember substructure dynamics module (SubDyn) within the new FAST modularization framework are introduced. SubDyn relies on two main engineering schematizations: 1) a linear frame finite-element beam (LFEB) model and 2) a dynamics system reduction via Craig-Bampton's method. A jacket support structure and an offshore system consisting of a turbine atop a jacket substructure were simulated to test the SubDyn module and to preliminarily assess results against results from a commercial finite-element code.

  4. Effects of bifunctional linker on the performance of P3HT/CdSe quantum dot-linker-ZnO nanocolumn photovoltaic device.

    PubMed

    Zeng, Tsung-Wei; Liu, Shuo; Hsu, Fang-Chi; Huang, Kuo-Tung; Liao, Hsuieh-Chung; Su, Wei-Fang

    2010-09-13

    We study the effects of bifunctional linker on the photovoltaic properties of P3HT/CdSe quantum dot-linker-ZnO nanocolumn heterostructure. The CdSe quantum dots are bound on the surface of ZnO nanocolumns through either aliphatic linker of 3-aminopropyl trimethoxysilane(APS) or aromatic linker of p-aminophenyl trimethoxysilane(APhS) using simple solution process. As compared to CdSe bound by aliphatic linker(APS), while CdSe is bound by aromatic linker(APhS), more than one fold increase of short circuit current density (J(SC)) of the device obtained under irradiance, which is attributed to a more efficient charge transfer dynamics at interface. In addition, the ZnO-APhS-CdSe/P3HT devices possess about 4.8 folds in power conversion efficiency as compared to ZnO/P3HT device as the results of reduction in shunt loss and interfacial recombination.

  5. Inspection of Asian Lacquer Substructures by Terahertz Time-Domain Imaging (THz-TDI)

    NASA Astrophysics Data System (ADS)

    Dandolo, Corinna Ludovica Koch; Fukunaga, Kaori; Kohzuma, Yoshei; Kiriyama, Kyoko; Matsuda, Kazutaka; Jepsen, Peter Uhd

    2016-11-01

    Lacquering is considered one of the most representative Asian artistic techniques. While the decorative part of lacquerwares is the lacquer itself, their substructures serve as the backbone of the object itself. Very little is known about these hidden substructures. Since lacquerwares are mostly composed of organic materials, such as urushi, wood, carbon black, and fabrics which are very X-ray transparent, standard X-ray radiography has some problems in achieving clear X-ray radiographic images. Therefore, we wanted to contribute to the understanding of the lacquer manufacturing technique by inspecting the substructures of Asian lacquerwares by means of THz time-domain imaging (THz-TDI). Three different kinds of Asian lacquerwares were examined by THz-TDI, and the outcomes have been compared with those obtained by standard X-radiography. THz-TDI provides unique information on lacquerwares substructures, aiding in the comprehension of the manufacturing technology yielding to these precious artefacts.

  6. 20. Top 30/3. Plan of exposed substructure elevations. Wyoming ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Top 30/3. Plan of exposed substructure elevations. - Wyoming Valley Flood Control System, Woodward Pumping Station, East of Toby Creek crossing by Erie-Lackawanna Railroad, Edwardsville, Luzerne County, PA

  7. Inspection of Asian Lacquer Substructures by Terahertz Time-Domain Imaging (THz-TDI)

    NASA Astrophysics Data System (ADS)

    Dandolo, Corinna Ludovica Koch; Fukunaga, Kaori; Kohzuma, Yoshei; Kiriyama, Kyoko; Matsuda, Kazutaka; Jepsen, Peter Uhd

    2017-04-01

    Lacquering is considered one of the most representative Asian artistic techniques. While the decorative part of lacquerwares is the lacquer itself, their substructures serve as the backbone of the object itself. Very little is known about these hidden substructures. Since lacquerwares are mostly composed of organic materials, such as urushi, wood, carbon black, and fabrics which are very X-ray transparent, standard X-ray radiography has some problems in achieving clear X-ray radiographic images. Therefore, we wanted to contribute to the understanding of the lacquer manufacturing technique by inspecting the substructures of Asian lacquerwares by means of THz time-domain imaging (THz-TDI). Three different kinds of Asian lacquerwares were examined by THz-TDI, and the outcomes have been compared with those obtained by standard X-radiography. THz-TDI provides unique information on lacquerwares substructures, aiding in the comprehension of the manufacturing technology yielding to these precious artefacts.

  8. Activity of a Two-Domain Antifreeze Protein Is Not Dependent on Linker Sequence

    PubMed Central

    Holland, Nolan B.; Nishimiya, Yoshiyuki; Tsuda, Sakae; Sönnichsen, Frank D.

    2007-01-01

    The reported NMR structure of RD3, a naturally occurring two-domain antifreeze protein, suggests that the two nearly identical domains are oriented to allow simultaneous binding of their active regions to the ice surface. It is implied that the nine residues linking the two domains play a role in this alignment, but this has not been established. We have designed and expressed a modified form of RD3 that replaces the nine-residue linker with a generic sequence of one serine and eight glycine residues to test the importance of the linker amino acid sequence. The modified linker is shown to have significantly different characteristics compared to the original linker. Heteronuclear nuclear Overhauser effect experiments show that the new linker residues have more mobility than the linker residues in the native protein. Further, NMR data show that the folding of the C-terminal domain is somewhat perturbed by the altered linker. Finally, distributions of residual dipolar couplings indicate that the two domains tumble and move independently of each other. Nevertheless, the thermal hysteresis activity of the modified protein is indistinguishable from that of native RD3, proving that increased activity of the two-domain antifreeze protein is not dependent on structure of the linker. PMID:17056724

  9. Multiple Tracers of Structure, Substructure, and Dynamics of Galaxy Halos

    NASA Astrophysics Data System (ADS)

    Romanowsky, Aaron

    2015-08-01

    I will present a suite of results on the fundamental properties of galaxy halos, using a variety of observational tracers for a range of galaxy types, from giant ellipticals to spirals to dwarfs, along with comparisons to numerical simulations. The tracers include diffuse stellar light spectroscopy up to ~4 Re, resolved stellar photometry and spectroscopy, metal-poor and metal-rich globular cluster subpopulations, and planetary nebulae. The results include extended rotation and metallicity profiles, scaling relations for total angular momentum, shape inferences for the halos, orbital anisotropy estimates, kinematically "decoupled" halos, surprisingly homogeneous total mass profiles, and both detection and chemodynamical mapping of streams, shells, and other substructures. Connections are made to simulations of idealized galaxy mergers and of full cosmological formation histories, using the observed properties to make inferences about the assembly mechanisms of individual galaxies and of different galaxy types. Detailed models of stellar streams are used to infer their progenitor properties and to probe the gravitational potentials of the host galaxies. Novel observations are presented of compact stellar systems (globular clusters, ultra-compact dwarfs, compact ellipticals, and transition objects), with implications for the merger histories of their host halos.

  10. Gravitational focusing and substructure effects on the rate modulation in direct dark matter searches

    SciTech Connect

    Nobile, Eugenio Del; Gelmini, Graciela B.; Witte, Samuel J.

    2015-08-21

    We study how gravitational focusing (GF) of dark matter by the Sun affects the annual and biannual modulation of the expected signal in non-directional direct dark matter searches, in the presence of dark matter substructure in the local dark halo. We consider the Sagittarius stream and a possible dark disk, and show that GF suppresses some, but not all, of the distinguishing features that would characterize substructure of the dark halo were GF neglected.

  11. Gravitational focusing and substructure effects on the rate modulation in direct dark matter searches

    SciTech Connect

    Nobile, Eugenio Del; Gelmini, Graciela B.; Witte, Samuel J. E-mail: gelmini@physics.ucla.edu

    2015-08-01

    We study how gravitational focusing (GF) of dark matter by the Sun affects the annual and biannual modulation of the expected signal in non-directional direct dark matter searches, in the presence of dark matter substructure in the local dark halo. We consider the Sagittarius stream and a possible dark disk, and show that GF suppresses some, but not all, of the distinguishing features that would characterize substructure of the dark halo were GF neglected.

  12. Gap comparison between single crown and three-unit bridge zirconia substructures

    PubMed Central

    Charoenchitt, Masnisa; Asvanund, Chanavut

    2014-01-01

    PURPOSE To compare marginal and internal gaps of zirconia substructure of single crowns with those of three-unit fixed dental prostheses. MATERIALS AND METHODS Standardized Co-Cr alloy simulated second premolar and second molar abutments were fabricated and subsequently duplicated into type-III dental stone for working casts. After that, all zirconia substructures were made using Lava™ system. Marginal and internal gaps were measured in 2 planes (mesial-distal plane and buccal-palatal plane) at 5 locations: marginal opening (MO), chamfer area (CA), axial wall (AW), cusp tip (CT) and mid-occlusal (OA) using Replica technique. RESULTS There were significant differences between gaps at all locations. The mean ± SD of marginal gap in premolar was 43.6 ± 0.4 µm and 46.5 ± 0.5 µm for single crown and 3-unit bridge substructure respectively. For molar substructure the mean ± SD of marginal gap was 48.5 ± 0.4 µm and 52.6 ± 0.4 µm for single crown and 3-unit bridge respectively. The largest gaps were found at the occlusal area, which was 150.5 ± 0.5 µm and 154.5 ± 0.4 µm for single and 3-unit bridge premolar substructures respectively and 146.5 ± 0.4 µm and 211.5 ± 0.4 µm for single and 3-unit bridge molar substructure respectively. CONCLUSION Independent-samples t-test showed significant differences of gap in zirconia substructure between single crowns and three-unit bridge (P<.001). Therefore, the span length has the effect on the fit of zirconia substructure that is fabricated using CAD/CAM technique especially at the occlusal area. PMID:25177467

  13. Statistics of magnification perturbations by substructure in the cold dark matter cosmological model

    SciTech Connect

    Rozo, Eduardo; Zentner, Andrew R.; Bertone, Gianfranco; Chen, Jacqueline; /KICP, Chicago /Chicago U., Astron. Astrophys. Ctr.

    2005-06-01

    We study the statistical properties of magnification perturbations by substructures in strong lensed systems using linear perturbation theory and an analytical substructure model including tidal truncation and a continuous substructure mass spectrum. We demonstrate that magnification perturbations are dominated by perturbers found within a tidal radius of an image, and that sizable magnification perturbations may arise from small, coherent contributions from several substructures within the lens halo. We find that the root-mean-square (rms) fluctuation of the magnification perturbation is {approx}10% to {approx}20% and both the average and rms perturbations are sensitive to the mass spectrum and density profile of the perturbers. Interestingly,we find that relative to a smooth model of the same mass, the average magnification in clumpy models is lower (higher) than that in smooth models for positive (negative) parity images. This is opposite from what is observed if one assumes that the image magnification predicted by the best-fit smooth model of a lens is a good proxy for what the observed magnification would have been if substructures were absent. While it is possible for this discrepancy to be resolved via nonlinear perturbers, we argue that a more likely explanation is that the assumption that the best-fit lens model is a good proxy for the magnification in the absence of substructure is not correct. We conclude that a better theoretical understanding of the predicted statistical properties of magnification perturbations by CDM substructure is needed in order to affirm that CDM substructures have been unambiguously detected.

  14. Application of Resin Transfer Molding to the Manufacture of Wind Turbine Blade Substructures. Final Report

    SciTech Connect

    Hedley, C. W.; Ritter, W. J.; Ashwill, T.

    2001-07-26

    The U.S. has generally lacked the capability for an iterative process of detailed structural design, manufacturing, and testing at the full blade level to achieve specific structural performance, cost, and weight targets. This project examined the effects that different composites processing methods had on the performance of representative blade substructures. In addition, the results of the testing of these substructures was used to validate NuMAD, the design tool developed at Sandia National Laboratories.

  15. Molecular Cross-Talk between Nonribosomal Peptide Synthetase Carrier Proteins and Unstructured Linker Regions.

    PubMed

    Harden, Bradley J; Frueh, Dominique P

    2017-01-24

    Nonribosomal peptide synthetases (NRPSs) employ multiple domains separated by linker regions to incorporate substrates into natural products. During synthesis, substrates are covalently tethered to carrier proteins that translocate between catalytic partner domains. The molecular parameters that govern translocation and associated linker remodeling remain unknown. Here, we used NMR to characterize the structure, dynamics, and invisible states of a peptidyl carrier protein flanked by its linkers. We showed that the N-terminal linker stabilizes and interacts with the protein core while modulating dynamics at specific sites involved in post-translational modifications and/or domain interactions. The results detail the molecular communication between peptidyl carrier proteins and their linkers and could guide efforts in engineering NRPSs to obtain new pharmaceuticals.

  16. Dipolar cross-linkers for PDMS networks with enhanced dielectric permittivity and low dielectric loss

    NASA Astrophysics Data System (ADS)

    Bahrt Madsen, Frederikke; Egede Daugaard, Anders; Hvilsted, Søren; Yahia Benslimane, Mohamed; Ladegaard Skov, Anne

    2013-10-01

    Dipole grafted cross-linkers were utilized to prepare polydimethylsiloxane (PDMS) elastomers with various chain lengths and with various concentrations of functional cross-linker. The grafted cross-linkers were prepared by reaction of two alkyne-functional dipoles, 1-ethynyl-4-nitrobenzene and 3-(4-((4-nitrophenyl)diazenyl)phenoxy)-prop-1-yn-1-ylium, with a synthesized silicone compatible azide-functional cross-linker by click chemistry. The thermal, mechanical and electromechanical properties were investigated for PDMS films with 0 to 3.6 wt% of dipole-cross-linker. The relative dielectric permittivity was found to increase by ∼20% at only 0.46 wt% of incorporated dipole without significant changes in the mechanical properties. Furthermore, the dielectric losses were proved to be remarkably low while the electrical breakdown strengths were high.

  17. Thermodynamic Insight in the High-Pressure Behavior of UiO-66: Effect of Linker Defects and Linker Expansion

    PubMed Central

    2016-01-01

    In this Article, we present a molecular-level understanding of the experimentally observed loss of crystallinity in UiO-66-type metal–organic frameworks, including the pristine UiO-66 to -68 as well as defect-containing UiO-66 materials, under the influence of external pressure. This goal is achieved by constructing pressure-versus-volume profiles at finite temperatures using a thermodynamic approach relying on ab initio derived force fields. On the atomic level, the phenomenon is reflected in a sudden drop in the number of symmetry operators for the crystallographic unit cell because of the disordered displacement of the organic linkers with respect to the inorganic bricks. For the defect-containing samples, a reduced mechanical stability is observed, however, critically depending on the distribution of these defects throughout the material, hence demonstrating the importance of judiciously characterizing defects in these materials. PMID:27594765

  18. Theoretical and software considerations for general dynamic analysis using multilevel substructured models

    NASA Technical Reports Server (NTRS)

    Schmidt, R. J.; Dodds, R. H., Jr.

    1985-01-01

    The dynamic analysis of complex structural systems using the finite element method and multilevel substructured models is presented. The fixed-interface method is selected for substructure reduction because of its efficiency, accuracy, and adaptability to restart and reanalysis. This method is extended to reduction of substructures which are themselves composed of reduced substructures. The implementation and performance of the method in a general purpose software system is emphasized. Solution algorithms consistent with the chosen data structures are presented. It is demonstrated that successful finite element software requires the use of software executives to supplement the algorithmic language. The complexity of the implementation of restart and reanalysis porcedures illustrates the need for executive systems to support the noncomputational aspects of the software. It is shown that significant computational efficiencies can be achieved through proper use of substructuring and reduction technbiques without sacrificing solution accuracy. The restart and reanalysis capabilities and the flexible procedures for multilevel substructured modeling gives economical yet accurate analyses of complex structural systems.

  19. Nuclear substructure reorganization during late stageerythropoiesis is selective and does not involve caspase cleavage ofmajor nuclear substructural proteins

    SciTech Connect

    Krauss, Sharon Wald; Lo, Annie J.; Short, Sarah A.; Koury, MarkJ.; Mohandas, Narla; Chasis, Joel Anne

    2005-04-06

    Enucleation, a rare feature of mammalian differentiation, occurs in three cell types: erythroblasts, lens epithelium and keratinocytes. Previous investigations suggest that caspase activation functions in lens epithelial and keratinocyte enucleation, as well as in early erythropoiesis encompassing BFU-E differentiation to proerythroblast. To determine whether caspase activation contributes to later erythropoiesis and whether nuclear substructures other than chromatin reorganize, we analyzed distributions of nuclear subcompartment proteins and assayed for caspase-induced cleavage of subcompartmental target proteins in mouse erythroblasts. We found that patterns of lamin B in the filamentous network interacting with both the nuclear envelope and DNA, nuclear matrix protein NuMA, and splicing factors Sm and SC35 persisted during nuclear condensation, consistent with effective transcription of genes expressed late in differentiation. Thus nuclear reorganization prior to enucleation is selective, allowing maintenance of critical transcriptional processes independent of extensive chromosomal reorganization. Consistent with these data, we found no evidence for caspase-induced cleavage of major nuclear subcompartment proteins during late erythropoiesis, in contrast to what has been observed in early erythropoiesis and in lens epithelial and keratinocyte differentiation. These findings imply that nuclear condensation and extrusion during terminal erythroid differentiation involve novel mechanisms that do not entail major activation of apoptotic machinery.

  20. Self-assembling complexes between binary mixtures of lipids with different linkers and nucleic acids promote universal mRNA, DNA and siRNA delivery.

    PubMed

    Colombani, Thibault; Peuziat, Pauline; Dallet, Laurence; Haudebourg, Thomas; Mével, Mathieu; Berchel, Mathieu; Lambert, Olivier; Habrant, Damien; Pitard, Bruno

    2017-03-10

    Protein expression and RNA interference require efficient delivery of DNA or mRNA and small double stranded RNA into cells, respectively. Although cationic lipids are the most commonly used synthetic delivery vectors, a clear need still exists for a better delivery of various types of nucleic acids molecules to improve their biological activity. To optimize the transfection efficiency, a molecular approach consisting in modifying the chemical structure of a given cationic lipid is usually performed, but an alternative strategy could rely on modulating the supramolecular assembly of lipidic lamellar phases sandwiching the nucleic acids molecules. To validate this new concept, we synthesized on one hand two paromomycin-based cationic lipids, with either an amide or a phosphoramide linker, and on the other hand two imidazole-based neutral lipids, having as well either an amide or a phosphoramide function as linker. Combinations of cationic and helper lipids containing the same amide or phosphoramide linkers led to the formation of homogeneous lamellar phases, while hybrid lamellar phases were obtained when the linkers on the cationic and helper lipids were different. Cryo-transmission electron microscopy and fluorescence experiments showed that liposomes/nucleic acids complexes resulting from the association of nucleic acids with hybrid lamellar phases led to complexes that were more stable in the extracellular compartment compared to those obtained with homogeneous systems. In addition, we observed that the most active supramolecular assemblies for the delivery of DNA, mRNA and siRNA were obtained when the cationic and helper lipids possess linkers of different natures. The results clearly show that this supramolecular strategy modulating the property of the lipidic lamellar phase constitutes a new approach for increasing the delivery of various types of nucleic acid molecules.

  1. TGF-beta and HGF transmit the signals through JNK-dependent Smad2/3 phosphorylation at the linker regions.

    PubMed

    Mori, Shigeo; Matsuzaki, Koichi; Yoshida, Katsunori; Furukawa, Fukiko; Tahashi, Yoshiya; Yamagata, Hideo; Sekimoto, Go; Seki, Toshihito; Matsui, Hirofumi; Nishizawa, Mikio; Fujisawa, Jun-ichi; Okazaki, Kazuichi

    2004-09-23

    Although hepatocyte growth factor (HGF) can act synergistically or antagonistically with transforming growth factor-beta (TGF-beta) signaling, molecular mechanism of their crosstalk remains unknown. Using antibodies which selectively distinguished receptor-regulated Smads (R-Smads) phosphorylated at linker regions from those at C-terminal regions, we herein showed that either HGF or TGF-beta treatment of normal stomach-origin cells activated the JNK pathway, thereafter inducing endogenous R-Smads phosphorylation at linker regions. However, the phosphorylation at their C-terminal regions was not induced by HGF treatment. The activated JNK could directly phosphorylate R-Smads in vitro at the same sites that were phosphorylated in response to TGF-beta or HGF in vivo. Thus, the linker regions of R-Smads were the common phosphorylation sites for HGF and TGF-beta signaling pathways. The phosphorylation induced by simultaneous treatment with HGF and TGF-beta allowed R-Smads to associate with Smad4 and to translocate into the nucleus. JNK pathway involved HGF and TGF-beta-mediated infiltration potency since a JNK inhibitor SP600125 caused the reduction of invasive capacity induced by HGF and TGF-beta signals. Moreover, a combined treatment with HGF and TGF-beta led to a potent increase in plasminogen activator inhibitor type 1 transcriptional activity through Smad3 phosphorylation at the linker region. In contrast, HGF treatment reduced TGF-beta-dependent activation of p15INK4B promoter, in which Smad3 phosphorylation at the C-terminal region was involved. In conclusion, HGF and TGF-beta transmit the signals through JNK-mediated R-Smads phosphorylation at linker regions.

  2. Jet substructure using semi-inclusive jet functions in SCET

    NASA Astrophysics Data System (ADS)

    Kang, Zhong-Bo; Ringer, Felix; Vitev, Ivan

    2016-11-01

    We propose a new method to evaluate jet substructure observables in inclusive jet measurements, based upon semi-inclusive jet functions in the framework of Soft Collinear Effective Theory (SCET). As a first example, we consider the jet fragmentation function, where a hadron h is identified inside a fully reconstructed jet. We introduce a new semi-inclusive fragmenting jet function {{G}}_i^h(z={ω}_J/ω, {z}_h={ω}_h/{ω}_J,{ω}_J,R,μ ) , which depends on the jet radius R and the large light-cone momenta of the parton ` i' initiating the jet ( ω), the jet ( ω J ), and the hadron h ( ω h ). The jet fragmentation function can then be expressed as a semi-inclusive observable, in the spirit of actual experimental measurements, rather than as an exclusive one. We demonstrate the consistency of the effective field theory treatment and standard perturbative QCD calculations of this observable at next-to-leading order (NLO). The renormalization group (RG) equation for the semi-inclusive fragmenting jet function {{G}}_i^h(z,{z}_h,{ω}_J,R,μ ) are also derived and shown to follow exactly the usual timelike DGLAP evolution equations for fragmentation functions. The newly obtained RG equations can be used to perform the resummation of single logarithms of the jet radius parameter R up to next-to-leading logarithmic (NLL R ) accuracy. In combination with the fixed NLO calculation, we obtain NLO+NLL R results for the hadron distribution inside the jet. We present numerical results for pp → (jet h) X in the new framework, and find excellent agreement with existing LHC experimental data.

  3. Substructure method in high-speed monorail dynamic problems

    NASA Astrophysics Data System (ADS)

    Ivanchenko, I. I.

    2008-12-01

    combined schemes modeling a strained elastic compound moving structure and a monorail elevated track. The problems of development of methods for dynamic analysis of monorails are very topical, especially because of increasing speeds of the rolling stock motion. These structures are studied in [16-18]. In the present paper, the above problem is solved by using the method for the moving load analysis and a step procedure of integration with respect to time, which were proposed in [9, 19], respectively. Further, these components are used to enlarge the possibilities of the substructure method in problems of dynamics. In the approach proposed for moving load analysis of structures, for a substructure (having the shape of a boundary element or a superelement) we choose an object moving at a constant speed (a monorail rolling stock); in this case, we use rod boundary elements of large length, which are gathered in a system modeling these objects. In particular, sets of such elements form a model of a monorail rolling stock, namely, carriage hulls, wheeled carts, elements of the wheel spring suspension, models of continuous beams of monorail ways and piers with foundations admitting emergency subsidence and unilateral links. These specialized rigid finite elements with linear and nonlinear links, included into the set of earlier proposed finite elements [14, 19], permit studying unsteady vibrations in the "monorail train-elevated track" (MTET) system taking into account various irregularities on the beam-rail, the pier emergency subsidence, and their elastic support by the basement. In this case, a high degree of the structure spatial digitization is obtained by using rods with distributed parameters in the analysis. The displacements are approximated by linear functions and trigonometric Fourier series, which, as was already noted, permits increasing the number of degrees of freedom of the system under study simultaneously preserving the order of the resolving system of

  4. Stability, Intracellular Delivery, and Release of siRNA from Chitosan Nanoparticles Using Different Cross-Linkers

    PubMed Central

    Abdul Ghafoor Raja, Maria; Katas, Haliza; Jing Wen, Thum

    2015-01-01

    Chitosan (CS) nanoparticles have been extensively studied for siRNA delivery; however, their stability and efficacy are highly dependent on the types of cross-linker used. To address this issue, three common cross-linkers; tripolyphosphate (TPP), dextran sulphate (DS) and poly-D-glutamic acid (PGA) were used to prepare siRNA loaded CS-TPP/DS/PGA nanoparticles by ionic gelation method. The resulting nanoparticles were compared with regard to their physicochemical properties including particle size, zeta potential, morphology, binding and encapsulation efficiencies. Among all the formulations prepared with different cross linkers, CS-TPP-siRNA had the smallest particle size (ranged from 127 ± 9.7 to 455 ± 12.9 nm) with zeta potential ranged from +25.1 ± 1.5 to +39.4 ± 0.5 mV, and high entrapment (>95%) and binding efficiencies. Similarly, CS-TPP nanoparticles showed better siRNA protection during storage at 4˚C and as determined by serum protection assay. TEM micrographs revealed the assorted morphology of CS-TPP-siRNA nanoparticles in contrast to irregular morphology displayed by CS-DS-siRNA and CS-PGA-siRNA nanoparticles. All siRNA loaded CS-TPP/DS/PGA nanoparticles showed initial burst release followed by sustained release of siRNA. Moreover, all the formulations showed low and concentration-dependent cytotoxicity with human colorectal cancer cells (DLD-1), in vitro. The cellular uptake studies with CS-TPP-siRNA nanoparticles showed successful delivery of siRNA within cytoplasm of DLD-1 cells. The results demonstrate that ionically cross-linked CS-TPP nanoparticles are biocompatible non-viral gene delivery system and generate a solid ground for further optimization studies, for example with regard to steric stabilization and targeting. PMID:26068222

  5. NMR studies of DNA duplexes singly cross-linked by different synthetic linkers.

    PubMed Central

    Altmann, S; Labhardt, A M; Bur, D; Lehmann, C; Bannwarth, W; Billeter, M; Wüthrich, K; Leupin, W

    1995-01-01

    Molecular modelling studies resulted in the design of a variety of non-nucleotidic covalent linkers to bridge the 3'-end of the (+)-strand and the 5'-end of the (-)-strand in DNA duplexes. Three of these linkers were synthesized and used to prepare singly cross-linked duplexes d(GTGGAATTC)-linker-d(GAATTCCAC). Linker I is an assembly of a propylene-, a phosphate- and a second propylene-group and is thought to mimic the backbone of two nucleotides. Linkers II and III consist of five and six ethyleneglycol units, respectively. The melting temperatures of the cross-linked duplexes are 65 degrees C for I and 73 degrees C for II and III, as compared with 36 degrees C for the corresponding non-linked nonadeoxynucleotide duplex. The three cross-linked duplexes were structurally characterized by nuclear magnetic resonance spectroscopy. The 1H and 31P resonance assignments in the DNA stem were obtained using standard methods. For the resonance assignment of the linker protons, two-dimensional 1H-31P heteronuclear COSY and two-quantum-experiments were used. Distance geometry calculations with NOE-derived distance constraints were performed and the resulting structures were energy-minimized. In duplex I, the nucleotides flanking the propylene-phosphate-propylene-linker do not form a Watson-Crick base pair, whereas in duplexes II and III the entire DNA stem is in a B-type double helix conformation. Images PMID:8532525

  6. Effect of linker structure on surface density of aptamer monolayers and their corresponding protein binding efficiency.

    PubMed

    Balamurugan, Subramanian; Obubuafo, Anne; McCarley, Robin L; Soper, Steven A; Spivak, David A

    2008-12-15

    A systematic study is reported on the effect of linker size and its chemical composition toward ligand binding to a surface-immobilized aptamer, measured using surface plasmon resonance. The results, using thrombin as the model system, showed that as the number of thymidine (T) units in the linker increases from 0 to 20 in four separate increments (T(0), T(5), T(10), T(20)), the surface density of the aptamer decreased linearly from approximately 25 to 12 pmol x cm(-2). The decrease in aptamer surface density occurred due to the increased size of the linker molecules. In addition, thrombin binding capacity was shown to increase as the linker length increased from 0 to 5 thymidine nucleotides and then decreased as the number of thymidine residues increased to 20 due to a balance between two different effects. The initial increase was due to increased access of thrombin to the aptamer as the aptamer was moved away from the surface. For linkers greater in length than T(5), the overall decrease in binding capacity was primarily due to a decrease in the surface density. Incorporation of a hexa(ethylene glycol) moiety into the linker did not affect the surface density but increased the amount of thrombin bound. In addition, the attachment of the linker at the 3'- versus the 5'-end of the aptamer resulted in increased aptamer surface density. However, monolayers formed with equal surface densities showed similar amounts of thrombin binding irrespective of the point of attachment.

  7. Increase of segmental mobility through insertion of a flexible linker in split point of firefly luciferase.

    PubMed

    Bahmani, Parisa; Hosseinkhani, Saman

    2017-01-01

    The crystal structure of Photinus pyralis luciferase shows a unique molecular architecture consisting of a large N-terminal domain and a small C-terminal domain which is separated by a wide cleft. Protein engineering methods attempts to design the peptide linkers that make a connection between different protein domains or subunits to allow for separating domains and improve kinetics and structural features of proteins. In regard to this; introduction of a flexible linker at split point of luciferase which has a strong self-association activity, may leads to conformational change and improve general flexibility of protein. In this study, two flexible linkers in the split point of luciferase are introduced in order to test the effect of linker on flexibility of luciferase activity. Glycine-rich linkers are introduced into P. pyralis firefly luciferase to make two separate mutant enzymes. Enzymatic properties of mutant and native forms were measured using luminescence assay. Results show that lengthening of luciferase domains through insertion of a flexible linker did not affect bioluminescence emission spectra. Also adding linkers do not have remarkable effect on thermostability. The Km values of mutants were increased compared to native form, indicating lower affinity of mutants toward substrates.

  8. Linker histone partial phosphorylation: effects on secondary structure and chromatin condensation.

    PubMed

    Lopez, Rita; Sarg, Bettina; Lindner, Herbert; Bartolomé, Salvador; Ponte, Inma; Suau, Pedro; Roque, Alicia

    2015-05-19

    Linker histones are involved in chromatin higher-order structure and gene regulation. We have successfully achieved partial phosphorylation of linker histones in chicken erythrocyte soluble chromatin with CDK2, as indicated by HPCE, MALDI-TOF and Tandem MS. We have studied the effects of linker histone partial phosphorylation on secondary structure and chromatin condensation. Infrared spectroscopy analysis showed a gradual increase of β-structure in the phosphorylated samples, concomitant to a decrease in α-helix/turns, with increasing linker histone phosphorylation. This conformational change could act as the first step in the phosphorylation-induced effects on chromatin condensation. A decrease of the sedimentation rate through sucrose gradients of the phosphorylated samples was observed, indicating a global relaxation of the 30-nm fiber following linker histone phosphorylation. Analysis of specific genes, combining nuclease digestion and qPCR, showed that phosphorylated samples were more accessible than unphosphorylated samples, suggesting local chromatin relaxation. Chromatin aggregation was induced by MgCl2 and analyzed by dynamic light scattering (DLS). Phosphorylated chromatin had lower percentages in volume of aggregated molecules and the aggregates had smaller hydrodynamic diameter than unphosphorylated chromatin, indicating that linker histone phosphorylation impaired chromatin aggregation. These findings provide new insights into the effects of linker histone phosphorylation in chromatin condensation.

  9. Linker histone partial phosphorylation: effects on secondary structure and chromatin condensation

    PubMed Central

    Lopez, Rita; Sarg, Bettina; Lindner, Herbert; Bartolomé, Salvador; Ponte, Inma; Suau, Pedro; Roque, Alicia

    2015-01-01

    Linker histones are involved in chromatin higher-order structure and gene regulation. We have successfully achieved partial phosphorylation of linker histones in chicken erythrocyte soluble chromatin with CDK2, as indicated by HPCE, MALDI-TOF and Tandem MS. We have studied the effects of linker histone partial phosphorylation on secondary structure and chromatin condensation. Infrared spectroscopy analysis showed a gradual increase of β-structure in the phosphorylated samples, concomitant to a decrease in α-helix/turns, with increasing linker histone phosphorylation. This conformational change could act as the first step in the phosphorylation-induced effects on chromatin condensation. A decrease of the sedimentation rate through sucrose gradients of the phosphorylated samples was observed, indicating a global relaxation of the 30-nm fiber following linker histone phosphorylation. Analysis of specific genes, combining nuclease digestion and qPCR, showed that phosphorylated samples were more accessible than unphosphorylated samples, suggesting local chromatin relaxation. Chromatin aggregation was induced by MgCl2 and analyzed by dynamic light scattering (DLS). Phosphorylated chromatin had lower percentages in volume of aggregated molecules and the aggregates had smaller hydrodynamic diameter than unphosphorylated chromatin, indicating that linker histone phosphorylation impaired chromatin aggregation. These findings provide new insights into the effects of linker histone phosphorylation in chromatin condensation. PMID:25870416

  10. Distinct binding properties of TIAR RRMs and linker region

    PubMed Central

    Kim, Henry S.; Headey, Stephen J.; Yoga, Yano M.K.; Scanlon, Martin J.; Gorospe, Myriam; Wilce, Matthew C.J.; Wilce, Jacqueline A.

    2013-01-01

    The RNA-binding protein TIAR is an mRNA-binding protein that acts as a translational repressor, particularly important under conditions of cellular stress. It binds to target mRNA and DNA via its RNA recognition motif (RRM) domains and is involved in both splicing regulation and translational repression via the formation of “stress granules.” TIAR has also been shown to bind ssDNA and play a role in the regulation of transcription. Here we show, using surface plasmon resonance and nuclear magnetic resonance spectroscopy, specific roles of individual TIAR domains for high-affinity binding to RNA and DNA targets. We confirm that RRM2 of TIAR is the major RNA- and DNA-binding domain. However, the strong nanomolar affinity binding to U-rich RNA and T-rich DNA depends on the presence of the six amino acid residues found in the linker region C-terminal to RRM2. On its own, RRM1 shows preferred binding to DNA over RNA. We further characterize the interaction between RRM2 with the C-terminal extension and an AU-rich target RNA sequence using NMR spectroscopy to identify the amino acid residues involved in binding. We demonstrate that TIAR RRM2, together with its C-terminal extension, is the major contributor for the high-affinity (nM) interactions of TIAR with target RNA sequences. PMID:23603827

  11. Distinct binding properties of TIAR RRMs and linker region.

    PubMed

    Kim, Henry S; Headey, Stephen J; Yoga, Yano M K; Scanlon, Martin J; Gorospe, Myriam; Wilce, Matthew C J; Wilce, Jacqueline A

    2013-04-01

    The RNA-binding protein TIAR is an mRNA-binding protein that acts as a translational repressor, particularly important under conditions of cellular stress. It binds to target mRNA and DNA via its RNA recognition motif (RRM) domains and is involved in both splicing regulation and translational repression via the formation of "stress granules." TIAR has also been shown to bind ssDNA and play a role in the regulation of transcription. Here we show, using surface plasmon resonance and nuclear magnetic resonance spectroscopy, specific roles of individual TIAR domains for high-affinity binding to RNA and DNA targets. We confirm that RRM2 of TIAR is the major RNA- and DNA-binding domain. However, the strong nanomolar affinity binding to U-rich RNA and T-rich DNA depends on the presence of the six amino acid residues found in the linker region C-terminal to RRM2. On its own, RRM1 shows preferred binding to DNA over RNA. We further characterize the interaction between RRM2 with the C-terminal extension and an AU-rich target RNA sequence using NMR spectroscopy to identify the amino acid residues involved in binding. We demonstrate that TIAR RRM2, together with its C-terminal extension, is the major contributor for the high-affinity (nM) interactions of TIAR with target RNA sequences.

  12. Paxillin-kinase-linker tyrosine phosphorylation regulates directional cell migration.

    PubMed

    Yu, Jianxin A; Deakin, Nicholas O; Turner, Christopher E

    2009-11-01

    Directed cell migration requires the coordination of growth factor and cell adhesion signaling and is of fundamental importance during embryonic development, wound repair, and pathological conditions such as tumor metastasis. Herein, we demonstrate that the ArfGAP, paxillin-kinase-linker (PKL/GIT2), is tyrosine phosphorylated in response to platelet-derived growth factor (PDGF) stimulation, in an adhesion dependent manner and is necessary for directed cell migration. Using a combination of pharmacological inhibitors, knockout cells and kinase mutants, FAK, and Src family kinases were shown to mediate PDGF-dependent PKL tyrosine phosphorylation. In fibroblasts, expression of a PKL mutant lacking the principal tyrosine phosphorylation sites resulted in loss of wound-induced cell polarization as well as directional migration. PKL phosphorylation was necessary for PDGF-stimulated PKL binding to the focal adhesion protein paxillin and expression of paxillin or PKL mutants defective in their respective binding motifs recapitulated the polarization defects. RNA interference or expression of phosphorylation mutants of PKL resulted in disregulation of PDGF-stimulated Rac1 and PAK activities, reduction of Cdc42 and Erk signaling, as well as mislocalization of betaPIX. Together these studies position PKL as an integral component of growth factor and cell adhesion cross-talk signaling, controlling the development of front-rear cell polarity and directional cell migration.

  13. Lecithin-Linker Microemulsion Gelatin Gels for Extended Drug Delivery

    PubMed Central

    Xuan, Xiao-Yue; Cheng, Yu-Ling; Acosta, Edgar

    2012-01-01

    This article introduces the formulation of alcohol-free, lecithin microemulsion-based gels (MBGs) prepared with gelatin as gelling agent. The influence of oil, water, lecithin and hydrophilic and lipophilic additives (linkers) on the rheological properties and appearance of these gels was systematically explored using ternary phase diagrams. Clear MBGs were obtained in regions of single phase microemulsions (μEs) at room temperature. Increasing the water content in the formulation increased the elastic modulus of the gels, while increasing the oil content had the opposite effect. The hydrophilic additive (PEG-6-caprylic/capric glycerides) was shown to reduce the elastic modulus of gelatin gels, particularly at high temperatures. In contrast to anionic (AOT) μEs, the results suggest that in lecithin (nonionic) μEs, the introduction of gelatin “dehydrates” the μE. Finally, when the transdermal transport of lidocaine formulated in the parent μE and the resulting MBG were compared, only a minor retardation in the loading and release of lidocaine was observed. PMID:24300183

  14. A new highly versatile handle for chemistry on a solid support: the pipecolic linker.

    PubMed

    Zajdel, Paweł; Nomezine, Gaël; Masurier, Nicolas; Amblard, Muriel; Pawłowski, Maciej; Martinez, Jean; Subra, Gilles

    2010-07-05

    The design, synthesis, and potential application of the pipecolic linker is presented. This new versatile handle can immobilize primary, secondary, and aromatic amines, as well as alcohols, phenols, and hydrazides, on a solid support. Compared with other linkers, the anchoring step is easy and efficient. The release of final products from the resin proceeds upon acidic treatment with high purities. The pipecolic linker offers the promise of being using in peptide chemistry to produce peptides modified at the N and C terminus, peptidomimetics, as well as small organic molecules.

  15. Flexibility of NS5 Methyltransferase-Polymerase Linker Region Is Essential for Dengue Virus Replication

    PubMed Central

    Zhao, Yongqian; Soh, Tingjin Sherryl; Chan, Kitti Wing Ki; Fung, Sarah Suet Yin; Swaminathan, Kunchithapadam; Lim, Siew Pheng; Shi, Pei-Yong; Huber, Thomas; Lescar, Julien

    2015-01-01

    We examined the function of the conserved Val/Ile residue within the dengue virus NS5 interdomain linker (residues 263 to 272) by site-directed mutagenesis. Gly substitution or Gly/Pro insertion after the conserved residue increased the linker flexibility and created slightly attenuated viruses. In contrast, Pro substitution abolished virus replication by imposing rigidity in the linker and restricting NS5's conformational plasticity. Our biochemical and reverse genetics experiments demonstrate that NS5 utilizes conformational regulation to achieve optimum viral replication. PMID:26269182

  16. Formulation of an experimental substructure model using a Craig-Bampton based transmission simulator

    NASA Astrophysics Data System (ADS)

    Kammer, Daniel C.; Allen, Mathew S.; Mayes, Randy L.

    2015-12-01

    Experimental-analytical substructuring is attractive when there is motivation to replace one or more system subcomponents with an experimental model. This experimentally derived substructure can then be coupled to finite element models of the rest of the structure to predict the system response. The transmission simulator method couples a fixture to the component of interest during a vibration test in order to improve the experimental model for the component. The transmission simulator is then subtracted from the tested system to produce the experimental component. The method reduces ill-conditioning by imposing a least squares fit of constraints between substructure modal coordinates to connect substructures, instead of directly connecting physical interface degrees of freedom. This paper presents an alternative means of deriving the experimental substructure model, in which a Craig-Bampton representation of the transmission simulator is created and subtracted from the experimental measurements. The corresponding modal basis of the transmission simulator is described by the fixed-interface modes, rather than free modes that were used in the original approach. These modes do a better job of representing the shape of the transmission simulator as it responds within the experimental system, leading to more accurate results using fewer modes. The new approach is demonstrated using a simple finite element model based example with a redundant interface.

  17. AN EXAMINATION OF THE OPTICAL SUBSTRUCTURE OF GALAXY CLUSTERS HOSTING RADIO SOURCES

    SciTech Connect

    Wing, Joshua D.; Blanton, Elizabeth L.

    2013-04-20

    Using radio sources from the Faint Images of the Radio Sky at Twenty-cm survey, and optical counterparts in the Sloan Digital Sky Survey, we have identified a large number of galaxy clusters. The radio sources within these clusters are driven by active galactic nuclei, and our cluster samples include clusters with bent, and straight, double-lobed radio sources. We also included a single-radio-component comparison sample. We examine these galaxy clusters for evidence of optical substructure, testing the possibility that bent double-lobed radio sources are formed as a result of large-scale cluster mergers. We use a suite of substructure analysis tools to determine the location and extent of substructure visible in the optical distribution of cluster galaxies, and compare the rates of substructure in clusters with different types of radio sources. We found no preference for significant substructure in clusters hosting bent double-lobed radio sources compared to those with other types of radio sources.

  18. Formulation of an experimental substructure model using a Craig-Bampton based transmission simulator

    SciTech Connect

    Kammer, Daniel C.; Allen, Matthew S.; Mayes, Randall L.

    2015-09-26

    An experimental–analytical substructuring is attractive when there is motivation to replace one or more system subcomponents with an experimental model. This experimentally derived substructure can then be coupled to finite element models of the rest of the structure to predict the system response. The transmission simulator method couples a fixture to the component of interest during a vibration test in order to improve the experimental model for the component. The transmission simulator is then subtracted from the tested system to produce the experimental component. This method reduces ill-conditioning by imposing a least squares fit of constraints between substructure modal coordinates to connect substructures, instead of directly connecting physical interface degrees of freedom. This paper presents an alternative means of deriving the experimental substructure model, in which a Craig–Bampton representation of the transmission simulator is created and subtracted from the experimental measurements. The corresponding modal basis of the transmission simulator is described by the fixed-interface modes, rather than free modes that were used in the original approach. Moreover, these modes do a better job of representing the shape of the transmission simulator as it responds within the experimental system, leading to more accurate results using fewer modes. The new approach is demonstrated using a simple finite element model based example with a redundant interface.

  19. Formulation of an experimental substructure model using a Craig-Bampton based transmission simulator

    DOE PAGES

    Kammer, Daniel C.; Allen, Matthew S.; Mayes, Randall L.

    2015-09-26

    An experimental–analytical substructuring is attractive when there is motivation to replace one or more system subcomponents with an experimental model. This experimentally derived substructure can then be coupled to finite element models of the rest of the structure to predict the system response. The transmission simulator method couples a fixture to the component of interest during a vibration test in order to improve the experimental model for the component. The transmission simulator is then subtracted from the tested system to produce the experimental component. This method reduces ill-conditioning by imposing a least squares fit of constraints between substructure modal coordinatesmore » to connect substructures, instead of directly connecting physical interface degrees of freedom. This paper presents an alternative means of deriving the experimental substructure model, in which a Craig–Bampton representation of the transmission simulator is created and subtracted from the experimental measurements. The corresponding modal basis of the transmission simulator is described by the fixed-interface modes, rather than free modes that were used in the original approach. Moreover, these modes do a better job of representing the shape of the transmission simulator as it responds within the experimental system, leading to more accurate results using fewer modes. The new approach is demonstrated using a simple finite element model based example with a redundant interface.« less

  20. An algebraic sub-structuring method for large-scale eigenvaluecalculation

    SciTech Connect

    Yang, C.; Gao, W.; Bai, Z.; Li, X.; Lee, L.; Husbands, P.; Ng, E.

    2004-05-26

    We examine sub-structuring methods for solving large-scalegeneralized eigenvalue problems from a purely algebraic point of view. Weuse the term "algebraic sub-structuring" to refer to the process ofapplying matrix reordering and partitioning algorithms to divide a largesparse matrix into smaller submatrices from which a subset of spectralcomponents are extracted and combined to provide approximate solutions tothe original problem. We are interested in the question of which spectralcomponentsone should extract from each sub-structure in order to producean approximate solution to the original problem with a desired level ofaccuracy. Error estimate for the approximation to the small esteigen pairis developed. The estimate leads to a simple heuristic for choosingspectral components (modes) from each sub-structure. The effectiveness ofsuch a heuristic is demonstrated with numerical examples. We show thatalgebraic sub-structuring can be effectively used to solve a generalizedeigenvalue problem arising from the simulation of an acceleratorstructure. One interesting characteristic of this application is that thestiffness matrix produced by a hierarchical vector finite elements schemecontains a null space of large dimension. We present an efficient schemeto deflate this null space in the algebraic sub-structuringprocess.

  1. Single-nucleotide polymorphism-gene intermixed networking reveals co-linkers connected to multiple gene expression phenotypes

    PubMed Central

    Gong, Bin-Sheng; Zhang, Qing-Pu; Zhang, Guang-Mei; Zhang, Shao-Jun; Zhang, Wei; Lv, Hong-Chao; Zhang, Fan; Lv, Sa-Li; Li, Chuan-Xing; Rao, Shao-Qi; Li, Xia

    2007-01-01

    Gene expression profiles and single-nucleotide polymorphism (SNP) profiles are modern data for genetic analysis. It is possible to use the two types of information to analyze the relationships among genes by some genetical genomics approaches. In this study, gene expression profiles were used as expression traits. And relationships among the genes, which were co-linked to a common SNP(s), were identified by integrating the two types of information. Further research on the co-expressions among the co-linked genes was carried out after the gene-SNP relationships were established using the Haseman-Elston sib-pair regression. The results showed that the co-expressions among the co-linked genes were significantly higher if the number of connections between the genes and a SNP(s) was more than six. Then, the genes were interconnected via one or more SNP co-linkers to construct a gene-SNP intermixed network. The genes sharing more SNPs tended to have a stronger correlation. Finally, a gene-gene network was constructed with their intensities of relationships (the number of SNP co-linkers shared) as the weights for the edges. PMID:18466544

  2. The Use of Aryl Hydrazide Linkers for the Solid Phase Synthesis of Chemically Modified Peptides

    SciTech Connect

    Woo, Y; Mitchell, A R; Camarero, J A

    2006-11-03

    Since Merrifield introduced the concept of solid phase synthesis in 1963 for the rapid preparation of peptides, a large variety of different supports and resin-linkers have been developed that improve the efficiency of peptide assembly and expand the myriad of synthetically feasible peptides. The aryl hydrazide is one of the most useful resin-linkers for the synthesis of chemically modified peptides. This linker is completely stable during Boc- and Fmoc-based solid phase synthesis and yet it can be cleaved under very mild oxidative conditions. The present article reviews the use of this valuable linker for the rapid and efficient synthesis of C-terminal modified peptides, head-to-tail cyclic peptides and lipidated peptides.

  3. Composite materials with metal oxide attached to lead chalcogenide nanocrystal quantum dots with linkers

    DOEpatents

    Fuke, Nobuhiro; Koposov, Alexey Y; Sykora, Milan; Hoch, Laura

    2014-12-16

    Composite materials useful for devices such as photoelectrochemical solar cells include a substrate, a metal oxide film on the substrate, nanocrystalline quantum dots (NQDs) of lead sulfide, lead selenide, and lead telluride, and linkers that attach the NQDs to the metal oxide film. Suitable linkers preserve the 1s absorption peak of the NQDs. A suitable linker has a general structure A-B-C where A is a chemical group adapted for binding to a MO.sub.x and C is a chemical group adapted for binding to a NQD and B is a divalent, rigid, or semi-rigid organic spacer moiety. Other linkers that preserve the 1s absorption peak may also be used.

  4. Tethering metal ions to photocatalyst particulate surfaces by bifunctional molecular linkers for efficient hydrogen evolution.

    PubMed

    Yu, Weili; Isimjan, Tayirjan; Del Gobbo, Silvano; Anjum, Dalaver H; Abdel-Azeim, Safwat; Cavallo, Luigi; Garcia-Esparza, Angel T; Domen, Kazunari; Xu, Wei; Takanabe, Kazuhiro

    2014-09-01

    A simple and versatile method for the preparation of photocatalyst particulates modified with effective cocatalysts is presented; the method involves the sequential soaking of photocatalyst particulates in solutions containing bifunctional organic linkers and metal ions. The modification of the particulate surfaces is a universal and reproducible method because the molecular linkers utilize strong covalent bonds, which in turn result in modified monolayer with a small but controlled quantity of metals. The photocatalysis results indicated that the CdS with likely photochemically reduced Pd and Ni, which were initially immobilized via ethanedithiol (EDT) as a linker, were highly efficient for photocatalytic hydrogen evolution from Na2S-Na2SO3-containing aqueous solutions. The method developed in this study opens a new synthesis route for the preparation of effective photocatalysts with various combinations of bifunctional linkers, metals, and photocatalyst particulate materials.

  5. Sequential Linker Installation: Precise Placement of Functional Groups in Multivariate Metal-Organic Frameworks

    SciTech Connect

    Yuan, S; Lu, WG; Chen, YP; Zhang, Q; Liu, TF; Feng, DW; Wang, X; Qin, JS; Zhou, HC

    2015-03-11

    A unique strategy, sequential linker installation (SLI), has been developed to construct multivariate MOFs with functional groups precisely positioned. PCN-700, a Zr-MOF with eight-connected Zr6O4(OH)(8)(H2O)(4) clusters, has been judiciously designed; the Zr-6 clusters in this MOF are arranged in such a fashion that, by replacement of terminal OH-/H2O ligands, subsequent insertion of linear dicarboxylate linkers is achieved. We demonstrate that linkers with distinct lengths and functionalities can be sequentially installed into PCN-700. Single-crystal to single-crystal transformation is realized so that the positions of the subsequently installed linkers are pinpointed via single-crystal X-ray diffraction analyses. This methodology provides a powerful tool to construct multivariate MOFs with precisely positioned functionalities in the desired proximity, which would otherwise be difficult to achieve.

  6. Two Principles of Reticular Chemistry Uncovered in a Metal-Organic Framework of Heterotritopic Linkers and Infinite Secondary Building Units.

    PubMed

    Catarineu, Noelle R; Schoedel, Alexander; Urban, Philipp; Morla, Maureen B; Trickett, Christopher A; Yaghi, Omar M

    2016-08-31

    Structural diversity of metal-organic frameworks (MOFs) has been largely limited to linkers with at most two different types of coordinating groups. MOFs constructed from linkers with three or more nonidentical coordinating groups have not been explored. Here, we report a robust and porous crystalline MOF, Zn3(PBSP)2 or MOF-910, constructed from a novel linker PBSP (phenylyne-1-benzoate, 3-benzosemiquinonate, 5-oxidopyridine) bearing three distinct types of coordinative functionality. The MOF adopts a complex and previously unreported topology termed tto. Our study suggests that simple, symmetric linkers are not a necessity for formation of crystalline extended structures and that new, more complex topologies are attainable with irregular, heterotopic linkers. This work illustrates two principles of reticular chemistry: first, selectivity for helical over straight rod secondary building units (SBUs) is achievable with polyheterotopic linkers, and second, the pitch of the resulting helical SBUs may be fine-tuned based on the metrics of the polyheterotopic linker.

  7. Chromatin fiber polymorphism triggered by variations of DNA linker lengths.

    PubMed

    Collepardo-Guevara, Rosana; Schlick, Tamar

    2014-06-03

    Deciphering the factors that control chromatin fiber structure is key to understanding fundamental chromosomal processes. Although details remain unknown, it is becoming clear that chromatin is polymorphic depending on internal and external factors. In particular, different lengths of the linker DNAs joining successive nucleosomes (measured in nucleosome-repeat lengths or NRLs) that characterize different cell types and cell cycle stages produce different structures. NRL is also nonuniform within single fibers, but how this diversity affects chromatin fiber structure is not clear. Here we perform Monte Carlo simulations of a coarse-grained oligonucleosome model to help interpret fiber structure subject to intrafiber NRL variations, as relevant to proliferating cells of interphase chromatin, fibers subject to remodeling factors, and regulatory DNA sequences. We find that intrafiber NRL variations have a profound impact on chromatin structure, with a wide range of different architectures emerging (highly bent narrow forms, canonical and irregular zigzag fibers, and polymorphic conformations), depending on the NRLs mixed. This stabilization of a wide range of fiber forms might allow NRL variations to regulate both fiber compaction and selective DNA exposure. The polymorphic forms spanning canonical to sharply bent structures, like hairpins and loops, arise from large NRL variations and are surprisingly more compact than uniform NRL structures. They are distinguished by tail-mediated far-nucleosome interactions, in addition to the near-nucleosome interactions of canonical 30-nm fibers. Polymorphism is consistent with chromatin's diverse biological functions and heterogeneous constituents. Intrafiber NRL variations, in particular, may contribute to fiber bending and looping and thus to distant communication in associated regulatory processes.

  8. THEORY AND SIMULATIONS OF REFRACTIVE SUBSTRUCTURE IN RESOLVED SCATTER-BROADENED IMAGES

    SciTech Connect

    Johnson, Michael D.; Gwinn, Carl R.

    2015-06-01

    At radio wavelengths, scattering in the interstellar medium distorts the appearance of astronomical sources. Averaged over a scattering ensemble, the result is a blurred image of the source. However, Narayan and Goodman and Goodman and Narayan showed that for an incomplete average, scattering introduces refractive substructure in the image of a point source that is both persistent and wideband. We show that this substructure is quenched but not smoothed by an extended source. As a result, when the scatter-broadening is comparable to or exceeds the unscattered source size, the scattering can introduce spurious compact features into images. In addition, we derive efficient strategies to numerically compute realistic scattered images, and we present characteristic examples from simulations. Our results show that refractive substructure is an important consideration for ongoing missions at the highest angular resolutions, and we discuss specific implications for RadioAstron and the Event Horizon Telescope.

  9. Theory and Simulations of Refractive Substructure in Resolved Scatter-broadened Images

    NASA Astrophysics Data System (ADS)

    Johnson, Michael D.; Gwinn, Carl R.

    2015-06-01

    At radio wavelengths, scattering in the interstellar medium distorts the appearance of astronomical sources. Averaged over a scattering ensemble, the result is a blurred image of the source. However, Narayan & Goodman and Goodman & Narayan showed that for an incomplete average, scattering introduces refractive substructure in the image of a point source that is both persistent and wideband. We show that this substructure is quenched but not smoothed by an extended source. As a result, when the scatter-broadening is comparable to or exceeds the unscattered source size, the scattering can introduce spurious compact features into images. In addition, we derive efficient strategies to numerically compute realistic scattered images, and we present characteristic examples from simulations. Our results show that refractive substructure is an important consideration for ongoing missions at the highest angular resolutions, and we discuss specific implications for RadioAstron and the Event Horizon Telescope.

  10. Three Dimensional Defect Reconstruction Using State Space Search and Woodbury's Substructure Method

    NASA Astrophysics Data System (ADS)

    Liu, X.; Deng, Y.; Li, Y.; Udpa, L.; Udpa, S. S.

    2010-02-01

    This paper introduces a model-based approach to reconstruct the three-dimensional defect profiles using eddy-current heat exchanger tube inspection signals. The method uses a Woodbury's substructure finite element forward model to simulate the underlying physics, a state space defect representation, and a tree search algorithm to solve the inverse problem. The advantage of the substructure method is that it divides the whole solution domain into two substructures and only the region of interest (ROI) with dramatic material changes will be updated in each iterative step. Since the number of elements inside the ROI is very small compared with the number of elements in the entire mesh, the computational effort needed in both LU factorization and coefficient matrix assembly is reduced. Therefore, the execution time is reduced significantly making the inversion very efficient. The initial inversion results are presented to confirm the validity of the approach.

  11. Exploring triad-rich substructures by graph-theoretic characterizations in complex networks

    NASA Astrophysics Data System (ADS)

    Jia, Songwei; Gao, Lin; Gao, Yong; Nastos, James; Wen, Xiao; Zhang, Xindong; Wang, Haiyang

    2017-02-01

    One of the most important problems in complex networks is how to detect communities accurately. The main challenge lies in the fact that traditional definition about communities does not always capture the intrinsic features of communities. Motivated by the observation that communities in PPI networks tend to consist of an abundance of interacting triad motifs, we define a 2-club substructure with diameter 2 possessing triad-rich property to describe a community. Based on the triad-rich substructure, we design a DIVision Algorithm using our proposed edge Niche Centrality DIVANC to detect communities effectively in complex networks. We also extend DIVANC to detect overlapping communities by proposing a simple 2-hop overlapping strategy. To verify the effectiveness of triad-rich substructures, we compare DIVANC with existing algorithms on PPI networks, LFR synthetic networks and football networks. The experimental results show that DIVANC outperforms most other algorithms significantly and, in particular, can detect sparse communities.

  12. Structural Studies of AAV2 Rep68 Reveal a Partially Structured Linker and Compact Domain Conformation

    PubMed Central

    Musayev, Faik N.; Zarate-Perez, Francisco; Bardelli, Martino; Bishop, Clayton; Saniev, Emil F.; Linden, R. Michael; Henckaerts, Els; Escalante, Carlos R.

    2015-01-01

    Adeno-associated virus (AAV) nonstructural proteins Rep78 and Rep68 carry out all DNA transactions that regulate the AAV life cycle. They share two multifunctional domains: an N-terminal origin binding/nicking domain (OBD) from the HUH superfamily and a SF3 helicase domain. A short linker of ~20 amino acids that is critical for oligomerization and function connects the two domains. Although X-ray structures of the AAV5 OBD and AAV2 helicase domains have been determined, information about the full-length protein and linker conformation is not known. This article presents the solution structure of AAV2 Rep68 using small-angle X-ray scattering (SAXS). We first determined the X-ray structures of the minimal AAV2 Rep68 OBD and of the OBD with the linker region. These X-ray structures reveal novel features that include a long C-terminal α-helix that protrudes from the core of the protein at a 45° angle and a partially structured linker. SAXS studies corroborate that the linker is not extended, and we show that a proline residue in the linker is critical for Rep68 oligomerization and function. SAXS-based rigid-body modeling of Rep68 confirms these observations, showing a compact arrangement of the two domains in which they acquire a conformation that positions key residues in all domains on one face of the protein, poised to interact with DNA. PMID:26314310

  13. Structural Studies of AAV2 Rep68 Reveal a Partially Structured Linker and Compact Domain Conformation.

    PubMed

    Musayev, Faik N; Zarate-Perez, Francisco; Bardelli, Martino; Bishop, Clayton; Saniev, Emil F; Linden, R Michael; Henckaerts, Els; Escalante, Carlos R

    2015-09-29

    Adeno-associated virus (AAV) nonstructural proteins Rep78 and Rep68 carry out all DNA transactions that regulate the AAV life cycle. They share two multifunctional domains: an N-terminal origin binding/nicking domain (OBD) from the HUH superfamily and a SF3 helicase domain. A short linker of ∼20 amino acids that is critical for oligomerization and function connects the two domains. Although X-ray structures of the AAV5 OBD and AAV2 helicase domains have been determined, information about the full-length protein and linker conformation is not known. This article presents the solution structure of AAV2 Rep68 using small-angle X-ray scattering (SAXS). We first determined the X-ray structures of the minimal AAV2 Rep68 OBD and of the OBD with the linker region. These X-ray structures reveal novel features that include a long C-terminal α-helix that protrudes from the core of the protein at a 45° angle and a partially structured linker. SAXS studies corroborate that the linker is not extended, and we show that a proline residue in the linker is critical for Rep68 oligomerization and function. SAXS-based rigid-body modeling of Rep68 confirms these observations, showing a compact arrangement of the two domains in which they acquire a conformation that positions key residues in all domains on one face of the protein, poised to interact with DNA.

  14. Novel regulation of Smad3 oligomerization and DNA binding by its linker domain.

    PubMed

    Vasilaki, Eleftheria; Siderakis, Manos; Papakosta, Paraskevi; Skourti-Stathaki, Konstantina; Mavridou, Sofia; Kardassis, Dimitris

    2009-09-08

    Smad proteins are key effectors of the transforming growth factor beta (TGFbeta) signaling pathway in mammalian cells. Smads are composed of two highly structured and conserved domains called Mad homology 1 (MH1) and 2 (MH2), which are linked together by a nonconserved linker region. The recent identification of phosphorylation sites and binding sites for ubiquitin ligases in the linker regions of TGFbeta and bone morphogenetic protein (BMP) receptor-regulated Smads suggested that the linker may contribute to the regulation of Smad function by facilitating cross-talks with other signaling pathways. In the present study, we have generated and characterized novel Smad3 mutants bearing individual substitutions of conserved and nonconserved amino acid residues within a previously described transcriptionally active linker fragment. Our analysis showed that the conserved linker amino acids glutamine 222 and proline 229 play important roles in Smad functions such as homo- and hetero-oligomerization, nuclear accumulation in response to TGFbeta stimulation, and DNA binding. Furthermore, a Smad3 mutant bearing a substitution of the nonconserved amino acid asparagine 218 to alanine displayed enhanced transactivation potential relative to wild type Smad3. Finally, Smad3 P229A inhibited TGFbeta signaling when overexpressed in mammalian cells. In conclusion, our data are in line with previous studies supporting an important regulatory role of the linker region of Smads in their function as key transducers of TGFbeta signaling.

  15. Role of the S4-S5 Linker in CNG Channel Activation

    PubMed Central

    Kusch, Jana; Zimmer, Thomas; Holschuh, Jascha; Biskup, Christoph; Schulz, Eckhard; Nache, Vasilica; Benndorf, Klaus

    2010-01-01

    Cyclic nucleotide-gated (CNG) channels mediate sensory signal transduction in retinal and olfactory cells. The channels are activated by the binding of cyclic nucleotides to a cyclic nucleotide-binding domain (CNBD) in the C-terminus that is located at the intracellular side. The molecular events translating the ligand binding to the pore opening are still unknown. We investigated the role of the S4-S5 linker in the activation process by quantifying its interaction with other intracellular regions. To this end, we constructed chimeric channels in which the N-terminus, the S4-S5 linker, the C-linker, and the CNBD of the retinal CNGA1 subunit were systematically replaced by the respective regions of the olfactory CNGA2 subunit. Macroscopic concentration-response relations were analyzed, yielding the apparent affinity to cGMP and the Hill coefficient. The degree of functional coupling of intracellular regions in the activation gating was determined by thermodynamic double-mutant cycle analysis. We observed that all four intracellular regions, including the relatively short S4-S5 linker, are involved in controlling the apparent affinity of the channel to cGMP and, moreover, in determining the degree of cooperativity between the subunits, as derived from the Hill coefficient. The interaction energies reveal an interaction of the S4-S5 linker with both the N-terminus and the C-linker, but no interaction with the CNBD. PMID:20959089

  16. Lactase persistence-related genetic variant: population substructure and health outcomes.

    PubMed

    Smith, George Davey; Lawlor, Debbie A; Timpson, Nic J; Baban, Jamil; Kiessling, Matt; Day, Ian N M; Ebrahim, Shah

    2009-03-01

    Lactase persistence is an autosomal-dominant trait that is common in European-derived populations. A basic tendency for lactase persistence to increase from the southeast to the northwest across European populations has been noted, but such trends within countries have not been extensively studied. We genotyped the C/T(-13910) variant (rs4988235) that constitutes the putatively causal allele for lactase persistence (T allele representing persistence) in a general population sample of 3344 women aged 60-79 years from 23 towns across Britain. We found an overall frequency of 0.253 for the C (lactase non-persistence) allele, but with considerable gradients of decreasing frequency from the south to the north and from the east to the west of Britain for this allele. Daily sunlight was positively related to C (non-persistence) allele prevalence. However, sunlight exposure and latitude are strongly correlated, and it was not possible to identify which is the primary factor statistically underlying the distribution of lactase persistence. The C/T(-13910) variant (rs4988235) was not related to drinking milk or bone health (although drinking milk itself was protective of bone health), and was essentially unrelated to a wide range of other lifestyle, health and demographic characteristics. One exception was general health being rated as being poor or fair, for which there was an odds ratio of 1.38 (1.04, 1.84) for women homozygous for the C allele; on adjustment for latitude and longitude of place of birth, this attenuated to 1.19 (0.87, 1.64). The lactase persistence variant could contribute to the examination of data for the existence of, and then statistical control for, population substructure in genetic association studies.

  17. Substructure procedure for including tile flexibility in stress analysis of shuttle thermal protection system

    NASA Technical Reports Server (NTRS)

    Giles, G. L.

    1980-01-01

    A substructure procedure to include the flexibility of the tile in the stress analysis of the shuttle thermal protection system (TPS) is described. In this procedure, the TPS is divided into substructures of (1) the tile which is modeled by linear finite elements and (2) the SIP which is modeled as a nonlinear continuum. This procedure was applied for loading cases of uniform pressure, uniform moment, and an aerodynamic shock on various tile thicknesses. The ratios of through-the-thickness stresses in the SIP which were calculated using a flexible tile compared to using a rigid tile were found to be less than 1.05 for the cases considered.

  18. Effect of temperature on the formation of creep substructure in sodium chloride single crystals

    NASA Technical Reports Server (NTRS)

    Raj, Sai V.; Pharr, George M.

    1992-01-01

    The effect of temperature on the substructure morphology and the cell and subgrain size was investigated experimentally in NaCl single crystals under creep in the temperature range 573-873 K. It is found that the effect of temperature on the cell and subgrain sizes is weak in comparison with the effect of stress. However, there was a qualitative change in the substructure morphology with temperature, with the cells and subgrains better defined at higher temperatures. The volume fraction of the cell boundaries decreased with increasing temperature, thereby indicating a refinement of the microstructure at higher temperatures.

  19. Multimodality in galaxy clusters from SDSS DR8: substructure and velocity distribution

    NASA Astrophysics Data System (ADS)

    Einasto, M.; Vennik, J.; Nurmi, P.; Tempel, E.; Ahvensalmi, A.; Tago, E.; Liivamägi, L. J.; Saar, E.; Heinämäki, P.; Einasto, J.; Martínez, V. J.

    2012-04-01

    Context. The study of the signatures of multimodality in groups and clusters of galaxies, an environment for most of the galaxies in the Universe, gives us information about the dynamical state of clusters and about merging processes, which affect the formation and evolution of galaxies, groups and clusters, and larger structures - superclusters of galaxies and the whole cosmic web. Aims: We search for the presence of substructure, a non-Gaussian, asymmetrical velocity distribution of galaxies, and large peculiar velocities of the main galaxies in clusters with at least 50 member galaxies, drawn from the SDSS DR8. Methods: We employ a number of 3D, 2D, and 1D tests to analyse the distribution of galaxies in clusters: 3D normal mixture modelling, the Dressler-Shectman test, the Anderson-Darling and Shapiro-Wilk tests, as well as the Anscombe-Glynn and the D'Agostino tests. We find the peculiar velocities of the main galaxies, and use principal component analysis to characterise our results. Results: More than 80% of the clusters in our sample have substructure according to 3D normal mixture modelling, and the Dressler-Shectman (DS) test shows substructure in about 70% of the clusters. The median value of the peculiar velocities of the main galaxies in clusters is 206 km s-1 (41% of the rms velocity). The velocities of galaxies in more than 20% of the clusters show significant non-Gaussianity. While multidimensional normal mixture modelling is more sensitive than the DS test in resolving substructure in the sky distribution of cluster galaxies, the DS test determines better substructure expressed as tails in the velocity distribution of galaxies (possible line-of-sight mergers). Richer, larger, and more luminous clusters have larger amount of substructure and larger (compared to the rms velocity) peculiar velocities of the main galaxies. Principal component analysis of both the substructure indicators and the physical parametres of clusters shows that galaxy clusters

  20. Parametric studies of stitching effectiveness for preventing substructure disbond

    NASA Technical Reports Server (NTRS)

    Flanagan, Gerry; Furrow, Keith

    1995-01-01

    A methodology is desired that will allow a designer to select appropriate amounts of through-thickness reinforcement needed to meet design requirements. The goal is to use a relatively simple analysis to minimize the amount of testing that needs to be performed, and to make test results from simple configurations applicable to more general structures. Using this methodology one should be able to optimize the selection of stitching materials, the weight of the yarn, and the stitching density. The analysis approach is to treat substructure disbond as a crack propagation problem. In this approach, the stitches have little influence until a delamination begins to grow. Once the delamination reaches, or extends beyond a stitch, the stitch serves to reduce the strain-energy-release-rate (G) at the crack tip for a given applied load. The reduced G can then be compared to the unstitched materials toughness to predict the load required to further extend the crack. The current model treats the stitch as a simple spring which responds to displacements in the vertical (through-thickness) direction. In concept, this approach is similar to that proposed by other authors. Test results indicate that the model should be refined to include the shearing stiffness of the stitch. The strain-energy-release-rate calculations are performed using a code which uses interconnected higher-order plates to model built-up composite cross-sections. When plates are stacked vertically, the interfacial tractions between the plates can be computed. The plate differential equations are solved in closed-form. The code, called SUBLAM, was developed as part of this section in one dimension. Because of this limitation, rows of stitches are treated as a two-dimensional sheet. The spring stiffness of a row of stitches can be estimated from the stitch material, weight, and density. As a practical and conservative approach, we can assume that the stitch is bonded until a crack passes the stitch location

  1. Histone H4 tail mediates allosteric regulation of nucleosome remodelling by linker DNA.

    PubMed

    Hwang, William L; Deindl, Sebastian; Harada, Bryan T; Zhuang, Xiaowei

    2014-08-14

    Imitation switch (ISWI)-family remodelling enzymes regulate access to genomic DNA by mobilizing nucleosomes. These ATP-dependent chromatin remodellers promote heterochromatin formation and transcriptional silencing by generating regularly spaced nucleosome arrays. The nucleosome-spacing activity arises from the dependence of nucleosome translocation on the length of extranucleosomal linker DNA, but the underlying mechanism remains unclear. Here we study nucleosome remodelling by human ATP-dependent chromatin assembly and remodelling factor (ACF), an ISWI enzyme comprising a catalytic subunit, Snf2h, and an accessory subunit, Acf1 (refs 2, 11 - 13). We find that ACF senses linker DNA length through an interplay between its accessory and catalytic subunits mediated by the histone H4 tail of the nucleosome. Mutation of AutoN, an auto-inhibitory domain within Snf2h that bears sequence homology to the H4 tail, abolishes the linker-length sensitivity in remodelling. Addition of exogenous H4-tail peptide or deletion of the nucleosomal H4 tail also diminishes the linker-length sensitivity. Moreover, Acf1 binds both the H4-tail peptide and DNA in an amino (N)-terminal domain dependent manner, and in the ACF-bound nucleosome, lengthening the linker DNA reduces the Acf1-H4 tail proximity. Deletion of the N-terminal portion of Acf1 (or its homologue in yeast) abolishes linker-length sensitivity in remodelling and leads to severe growth defects in vivo. Taken together, our results suggest a mechanism for nucleosome spacing where linker DNA sensing by Acf1 is allosterically transmitted to Snf2h through the H4 tail of the nucleosome. For nucleosomes with short linker DNA, Acf1 preferentially binds to the H4 tail, allowing AutoN to inhibit the ATPase activity of Snf2h. As the linker DNA lengthens, Acf1 shifts its binding preference to the linker DNA, freeing the H4 tail to compete AutoN off the ATPase and thereby activating ACF.

  2. A Genetic Screen and Transcript Profiling Reveal a Shared Regulatory Program for Drosophila Linker Histone H1 and Chromatin Remodeler CHD1

    PubMed Central

    Kavi, Harsh; Lu, Xingwu; Xu, Na; Bartholdy, Boris A.; Vershilova, Elena; Skoultchi, Arthur I.; Fyodorov, Dmitry V.

    2015-01-01

    Chromatin structure and activity can be modified through ATP-dependent repositioning of nucleosomes and posttranslational modifications of core histone tails within nucleosome core particles and by deposition of linker histones into the oligonucleosome fiber. The linker histone H1 is essential in metazoans. It has a profound effect on organization of chromatin into higher-order structures and on recruitment of histone-modifying enzymes to chromatin. Here, we describe a genetic screen for modifiers of the lethal phenotype caused by depletion of H1 in Drosophila melanogaster. We identify 41 mis-expression alleles that enhance and 20 that suppress the effect of His1 depletion in vivo. Most of them are important for chromosome organization, transcriptional regulation, and cell signaling. Specifically, the reduced viability of H1-depleted animals is strongly suppressed by ubiquitous mis-expression of the ATP-dependent chromatin remodeling enzyme CHD1. Comparison of transcript profiles in H1-depleted and Chd1 null mutant larvae revealed that H1 and CHD1 have common transcriptional regulatory programs in vivo. H1 and CHD1 share roles in repression of numerous developmentally regulated and extracellular stimulus-responsive transcripts, including immunity-related and stress response-related genes. Thus, linker histone H1 participates in various regulatory programs in chromatin to alter gene expression. PMID:25628309

  3. A Computer Process for Substructure Searches on Compound Structures Ciphered in the IUPAC Notation

    ERIC Educational Resources Information Center

    Polton, D. J.

    1972-01-01

    Computer programs have been written which enable substructure searches to be carried out on a file of compounds ciphered using a modified version of the IUPAC (Dyson) notation. The search system outlined is to be linked with one which uses input from the chemical structure typewriter. (3 references) (Author)

  4. Substructural changes during hot deformation of an Fe-26Cr ferritic stainless steel

    SciTech Connect

    Gao, F.; Xu, Y.; Song, B.; Xia, K.

    2000-01-01

    Dynamic softening and substructural changes during hot deformation of a ferritic Fe-26Cr stainless steel were studied. The flow stress increased to reach a steady state in all the cases and the steady-state stress decreased with decreasing Z, the Zener-Hollomon parameter. A constant subgrain size was observed to correspond to the steady-state flow and the steady-state subgrain size increased with decreasing Z. Substructure examinations revealed that elongated, pancake-shaped subgrains formed in the early stage of deformation. Straight sub-boundaries and equiaxed subgrains developed progressively with strain, leading eventually to a stable substructure at strains greater than 0.7. During deformation at 1,100 C, dynamic recrystallization occurred by the migration and coalescence of sub-boundaries. Dynamic recovery dominated during deformation at 900 C, resulting in the formation of fine equiaxed subgrains. Based on microstructural observations, the process of substructural changes during hot deformation was described by a schematic diagram.

  5. Property Graph vs RDF Triple Store: A Comparison on Glycan Substructure Search

    PubMed Central

    Alocci, Davide; Mariethoz, Julien; Horlacher, Oliver; Bolleman, Jerven T.; Campbell, Matthew P.; Lisacek, Frederique

    2015-01-01

    Resource description framework (RDF) and Property Graph databases are emerging technologies that are used for storing graph-structured data. We compare these technologies through a molecular biology use case: glycan substructure search. Glycans are branched tree-like molecules composed of building blocks linked together by chemical bonds. The molecular structure of a glycan can be encoded into a direct acyclic graph where each node represents a building block and each edge serves as a chemical linkage between two building blocks. In this context, Graph databases are possible software solutions for storing glycan structures and Graph query languages, such as SPARQL and Cypher, can be used to perform a substructure search. Glycan substructure searching is an important feature for querying structure and experimental glycan databases and retrieving biologically meaningful data. This applies for example to identifying a region of the glycan recognised by a glycan binding protein (GBP). In this study, 19,404 glycan structures were selected from GlycomeDB (www.glycome-db.org) and modelled for being stored into a RDF triple store and a Property Graph. We then performed two different sets of searches and compared the query response times and the results from both technologies to assess performance and accuracy. The two implementations produced the same results, but interestingly we noted a difference in the query response times. Qualitative measures such as portability were also used to define further criteria for choosing the technology adapted to solving glycan substructure search and other comparable issues. PMID:26656740

  6. Property Graph vs RDF Triple Store: A Comparison on Glycan Substructure Search.

    PubMed

    Alocci, Davide; Mariethoz, Julien; Horlacher, Oliver; Bolleman, Jerven T; Campbell, Matthew P; Lisacek, Frederique

    2015-01-01

    Resource description framework (RDF) and Property Graph databases are emerging technologies that are used for storing graph-structured data. We compare these technologies through a molecular biology use case: glycan substructure search. Glycans are branched tree-like molecules composed of building blocks linked together by chemical bonds. The molecular structure of a glycan can be encoded into a direct acyclic graph where each node represents a building block and each edge serves as a chemical linkage between two building blocks. In this context, Graph databases are possible software solutions for storing glycan structures and Graph query languages, such as SPARQL and Cypher, can be used to perform a substructure search. Glycan substructure searching is an important feature for querying structure and experimental glycan databases and retrieving biologically meaningful data. This applies for example to identifying a region of the glycan recognised by a glycan binding protein (GBP). In this study, 19,404 glycan structures were selected from GlycomeDB (www.glycome-db.org) and modelled for being stored into a RDF triple store and a Property Graph. We then performed two different sets of searches and compared the query response times and the results from both technologies to assess performance and accuracy. The two implementations produced the same results, but interestingly we noted a difference in the query response times. Qualitative measures such as portability were also used to define further criteria for choosing the technology adapted to solving glycan substructure search and other comparable issues.

  7. Substructures in DAFT/FADA survey clusters based on XMM and optical data

    NASA Astrophysics Data System (ADS)

    Durret, F.; DAFT/FADA Team

    2014-07-01

    The DAFT/FADA survey was initiated to perform weak lensing tomography on a sample of 90 massive clusters in the redshift range [0.4,0.9] with HST imaging available. The complementary deep multiband imaging constitutes a high quality imaging data base for these clusters. In X-rays, we have analysed the XMM-Newton and/or Chandra data available for 32 clusters, and for 23 clusters we fit the X-ray emissivity with a beta-model and subtract it to search for substructures in the X-ray gas. This study was coupled with a dynamical analysis for the 18 clusters with at least 15 spectroscopic galaxy redshifts in the cluster range, based on a Serna & Gerbal (SG) analysis. We detected ten substructures in eight clusters by both methods (X-rays and SG). The percentage of mass included in substructures is found to be roughly constant with redshift, with values of 5-15%. Most of the substructures detected both in X-rays and with the SG method are found to be relatively recent infalls, probably at their first cluster pericenter approach.

  8. Modelling and control issues of dynamically substructured systems: adaptive forward prediction taken as an example

    PubMed Central

    Tu, Jia-Ying; Hsiao, Wei-De; Chen, Chih-Ying

    2014-01-01

    Testing techniques of dynamically substructured systems dissects an entire engineering system into parts. Components can be tested via numerical simulation or physical experiments and run synchronously. Additional actuator systems, which interface numerical and physical parts, are required within the physical substructure. A high-quality controller, which is designed to cancel unwanted dynamics introduced by the actuators, is important in order to synchronize the numerical and physical outputs and ensure successful tests. An adaptive forward prediction (AFP) algorithm based on delay compensation concepts has been proposed to deal with substructuring control issues. Although the settling performance and numerical conditions of the AFP controller are improved using new direct-compensation and singular value decomposition methods, the experimental results show that a linear dynamics-based controller still outperforms the AFP controller. Based on experimental observations, the least-squares fitting technique, effectiveness of the AFP compensation and differences between delay and ordinary differential equations are discussed herein, in order to reflect the fundamental issues of actuator modelling in relevant literature and, more specifically, to show that the actuator and numerical substructure are heterogeneous dynamic components and should not be collectively modelled as a homogeneous delay differential equation. PMID:25104902

  9. Modelling and control issues of dynamically substructured systems: adaptive forward prediction taken as an example.

    PubMed

    Tu, Jia-Ying; Hsiao, Wei-De; Chen, Chih-Ying

    2014-08-08

    Testing techniques of dynamically substructured systems dissects an entire engineering system into parts. Components can be tested via numerical simulation or physical experiments and run synchronously. Additional actuator systems, which interface numerical and physical parts, are required within the physical substructure. A high-quality controller, which is designed to cancel unwanted dynamics introduced by the actuators, is important in order to synchronize the numerical and physical outputs and ensure successful tests. An adaptive forward prediction (AFP) algorithm based on delay compensation concepts has been proposed to deal with substructuring control issues. Although the settling performance and numerical conditions of the AFP controller are improved using new direct-compensation and singular value decomposition methods, the experimental results show that a linear dynamics-based controller still outperforms the AFP controller. Based on experimental observations, the least-squares fitting technique, effectiveness of the AFP compensation and differences between delay and ordinary differential equations are discussed herein, in order to reflect the fundamental issues of actuator modelling in relevant literature and, more specifically, to show that the actuator and numerical substructure are heterogeneous dynamic components and should not be collectively modelled as a homogeneous delay differential equation.

  10. Strategic Considerations in the Design of a Screening System for Substructure Searches of Chemical Structure Files

    ERIC Educational Resources Information Center

    Adamson, George W.; And Others

    1973-01-01

    A major problem in the design of screening systems for substructure searches of chemical structure files is the development of a methodology for selection of an optimal set of structural characteristics to act as screens. Distributions of several structural characteristics of the Chemical Abstracts Service Registry System are summarized. (13…

  11. Common Cold

    MedlinePlus

    ... nose, coughing - everyone knows the symptoms of the common cold. It is probably the most common illness. In ... avoid colds. There is no cure for the common cold. For relief, try Getting plenty of rest Drinking ...

  12. Tuning cooperativity by controlling the linker length of silica-supported amines in catalysis and CO2 capture.

    PubMed

    Brunelli, Nicholas A; Didas, Stephanie A; Venkatasubbaiah, Krishnan; Jones, Christopher W

    2012-08-29

    Cooperative interactions between aminoalkylsilanes and silanols on a silica surface can be controlled by varying the length of the alkyl linker attaching the amine to the silica surface from C1 (methyl) to C5 (pentyl). The linker length strongly affects the catalytic cooperativity of amines and silanols in aldol condensations as well as the adsorptive cooperativity for CO(2) capture. The catalytic cooperativity increases with the linker length up to propyl (C3), with longer, more flexible linkers (up to C5) providing no additional benefit or hindrance. Short linkers (C1 and C2) limit the beneficial amine-silanol cooperativity in aldol condensations, resulting in lower catalytic rates than with the C3+ linkers. For the same materials, the adsorptive cooperativity exhibits similar trends for CO(2) capture efficiency.

  13. Chemical and enzymatic stability of amino acid prodrugs containing methoxy, ethoxy and propylene glycol linkers.

    PubMed

    Gupta, Deepak; Gupta, Sheeba Varghese; Lee, Kyung-Dall; Amidon, Gordon L

    2009-01-01

    We evaluated the chemical and enzymatic stabilities of prodrugs containing methoxy, ethoxy and propylene glycol linkers in order to find a suitable linker for prodrugs of carboxylic acids with amino acids. l-Valine and l-phenylalanine prodrugs of model compounds (benzoic acid and phenyl acetic acid) containing methoxy, ethoxy and propylene glycol linkers were synthesized. The hydrolysis rate profile of each compound was studied at physiologically relevant pHs (1.2, 4, 6 and 7.4). Enzymatic hydrolysis of propylene glycol containing compounds was studied using Caco-2 homogenate as well as purified enzyme valacyclovirase. It was observed that the stability of the prodrugs increases with the linker length (propyl > ethyl > methyl). The model prodrugs were stable at acidic pH as compared to basic pH. It was observed that the prodrug with the aliphatic amino acid promoiety was more stable compared to its aromatic counterpart. The comparison between benzyl and the phenyl model compounds revealed that the amino acid side chain is significant in determining the stability of the prodrug whereas the benzyl or phenyl carboxylic acid had little or no effect on the stability. The enzymatic activation studies of propylene glycol linker prodrug in the presence of valacyclovirase and cell homogenate showed faster generation of the parent drug at pH 7.4. The half-life of prodrugs at pH 7.4 was more than 12 h, whereas in the presence of cell homogenate the half-lives were less than 1 h. Hydrolysis by Caco-2 homogenate generated the parent compound in two steps, where the prodrug was first converted to the intermediate, propylene glycol benzoate, which was then converted to the parent compound (benzoic acid). Enzymatic hydrolysis of propylene glycol containing prodrugs by valacyclovirase showed hydrolysis of the amino acid ester part to generate the propylene glycol ester of model compound (propylene glycol benzoate) as the major product. The amino acid prodrugs containing methoxy

  14. A quantitative investigation of linker histone interactions with nucleosomes and chromatin.

    PubMed

    White, Alison E; Hieb, Aaron R; Luger, Karolin

    2016-01-11

    Linker histones such as H1 are abundant basic proteins that bind tightly to nucleosomes, thereby acting as key organizers of chromatin structure. The molecular details of linker histone interactions with the nucleosome, and in particular the contributions of linker DNA and of the basic C-terminal tail of H1, are controversial. Here we combine rigorous solution-state binding assays with native gel electrophoresis and Atomic Force Microscopy, to quantify the interaction of H1 with chromatin. We find that H1 binds nucleosomes and nucleosomal arrays with very tight affinity by recognizing a specific DNA geometry minimally consisting of a solitary nucleosome with a single ~18 base pair DNA linker arm. The association of H1 alters the conformation of trinucleosomes so that only one H1 can bind to the two available linker DNA regions. Neither incorporation of the histone variant H2A.Z, nor the presence of neighboring nucleosomes affects H1 affinity. Our data provide a comprehensive thermodynamic framework for this ubiquitous chromatin architectural protein.

  15. A High-Throughput Small Molecule Screen for C. elegans Linker Cell Death Inhibitors

    PubMed Central

    Schwendeman, Andrew R.; Shaham, Shai

    2016-01-01

    Programmed cell death is a ubiquitous process in metazoan development. Apoptosis, one cell death form, has been studied extensively. However, mutations inactivating key mammalian apoptosis regulators do not block most developmental cell culling, suggesting that other cell death pathways are likely important. Recent work in the nematode Caenorhabditis elegans identified a non-apoptotic cell death form mediating the demise of the male-specific linker cell. This cell death process (LCD, linker cell-type death) is morphologically conserved, and its molecular effectors also mediate axon degeneration in mammals and Drosophila. To develop reagents to manipulate LCD, we established a simple high-throughput screening protocol for interrogating the effects of small molecules on C. elegans linker cell death in vivo. From 23,797 compounds assayed, 11 reproducibly block linker cell death onset. Of these, five induce animal lethality, and six promote a reversible developmental delay. These results provide proof-of principle validation of our screening protocol, demonstrate that developmental progression is required for linker cell death, and suggest that larger scale screens may identify LCD-specific small-molecule regulators that target the LCD execution machinery. PMID:27716809

  16. The measles virus phosphoprotein interacts with the linker domain of STAT1

    SciTech Connect

    Devaux, Patricia Priniski, Lauren; Cattaneo, Roberto

    2013-09-15

    The measles virus (MV) phosphoprotein (P) and V proteins block the interferon (IFN) response by impeding phosphorylation of the signal transducer and activator of transcription 1 (STAT1) by the Janus kinase 1 (JAK1). We characterized how STAT1 mutants interact with P and JAK1 phosphorylation. Certain mutants of the linker, the Src-homology 2 domain (SH2), or the transactivation domain had reduced or abolished phosphorylation through JAK1 after IFN treatment. Other mutants, mainly localized in the linker, failed to interact with P as documented by the lack of interference with nuclear translocation. Thus the functional footprint of P on STAT1 localizes mainly to the linker domain; there is also some overlap with the STAT1 phosphorylation functional footprint on the SH2 domain. Based on these observations, we discuss how the MV-P might operate to inhibit the JAK/STAT pathway. - Highlights: • Residue in the linker and SH2 domains of STAT1 are important for MV-P interaction. • Residue in the linker and SH2 domains of STAT1 are important for STAT1 phosphorylation. • Residues interferring with both functions have similar location on STAT1. • The viral P and V proteins may operate in concert to inhibit the JAK/STAT pathway.

  17. Importance of the Linker Region in Matrix Metalloproteinase-1 Domain Interactions

    PubMed Central

    Singh, Warispreet; Fields, Gregg B.; Christov, Christo Z.; Karabencheva-Christova, Tatyana G.

    2016-01-01

    Collagenolysis is catalyzed by enzymes from the matrix metalloproteinase (MMP) family, where one of the most studied is MMP-1. The X-ray crystallographic structure of MMP-1 complexed with a collagen-model triple-helical peptide (THP) provided important atomistic information, but few details on the effects of the conformational flexibility on catalysis. In addition, the role of the linker region between the catalytic (CAT) and hemopexin-like (HPX) domains was not defined. In order to reveal the dynamics and correlations of MMP-1 comprehensive atomistic molecular dynamics simulations of an MMP-1•THP complex was performed. To examine the role of the linker region for MMP-1 function simulations with linker regions from MT1-MMP/MMP-14 and MMP-13 replacing the MMP-1 linker region were performed. The MD studies were in good agreement with the experimental observation that in the MMP-1•THP X-ray crystallographic structure MMP-1 is in a “closed” conformation. MD revealed that the interactions of the THP with the both the CAT and HPX domains of MMP-1 are dynamic in nature, and the linker region of MMP-1 influences the interactions and dynamics of both the CAT and HPX domains and collagen binding to MMP-1. PMID:26998255

  18. Mechanically Interlocked Linkers inside Metal-Organic Frameworks: Effect of Ring Size on Rotational Dynamics.

    PubMed

    Vukotic, V Nicholas; O'Keefe, Christopher A; Zhu, Kelong; Harris, Kristopher J; To, Christine; Schurko, Robert W; Loeb, Stephen J

    2015-08-05

    A series of metal-organic framework (MOF) materials has been prepared, each containing a mechanically interlocked molecule (MIM) as the linker and a copper(II) paddlewheel as the secondary building unit (SBU). The MIM linkers are [2]rotaxanes with varying sizes of crown ether macrocycles ([22]crown-6, 22C6; [24]crown-6, 24C6; [26]crown-6, 26C6; benzo[24]crown-6, B24C6) and an anilinium-based axle containing four carboxylate donor groups. Herein, the X-ray structures of MOFs UWCM-1 (no crown) and UWDM-1(22) are compared and demonstrate the effect of including a macrocycle around the axle of the linker. The rotaxane linkers are linear and result in nbo-type MOFs with void space that allows for motion of the interlocked macrocycle inside the MOF pores, while the macrocycle-free linker is bent and yields a MOF with a novel 12-connected bcc structure. Variable temperature (2)H solid-state nuclear magnetic resonance showed that the macrocycles in UWDM-1(22), UWDM-1(24), and UWDM-1(B24) undergo different degrees and rates of rotation depending on the size and shape of the macrocycle.

  19. A Partial Calcium-Free Linker Confers Flexibility to Inner-Ear Protocadherin-15.

    PubMed

    Powers, Robert E; Gaudet, Rachelle; Sotomayor, Marcos

    2017-03-07

    Tip links of the inner ear are protein filaments essential for hearing and balance. Two atypical cadherins, cadherin-23 and protocadherin-15, interact in a Ca(2+)-dependent manner to form tip links. The largely unknown structure and mechanics of these proteins are integral to understanding how tip links pull on ion channels to initiate sensory perception. Protocadherin-15 has 11 extracellular cadherin (EC) repeats. Its EC3-4 linker lacks several of the canonical Ca(2+)-binding residues, and contains an aspartate-to-alanine polymorphism (D414A) under positive selection in East Asian populations. We present structures of protocadherin-15 EC3-5 featuring two Ca(2+)-binding linker regions: canonical EC4-5 linker binding three Ca(2+) ions, and non-canonical EC3-4 linker binding only two Ca(2+) ions. Our structures and biochemical assays reveal little difference between the D414 and D414A variants. Simulations predict that the partial Ca(2+)-free EC3-4 linker exhibits increased flexural flexibility without compromised mechanical strength, providing insight into the dynamics of tip links and other atypical cadherins.

  20. Functional Interactions Between A' Helices in the C-linker of Open CNG Channels

    PubMed Central

    Hua, Li; Gordon, Sharona E.

    2005-01-01

    Cyclic nucleotide-gated (CNG) channels are nonselective cation channels that are activated by the direct binding of the cyclic nucleotides cAMP and cGMP. The region linking the last membrane-spanning region (S6) to the cyclic nucleotide binding domain in the COOH terminus, termed the C-linker, has been shown to play an important role in coupling cyclic nucleotide binding to opening of the pore. In this study, we explored the intersubunit proximity between the A' helices of the C-linker regions of CNGA1 in functional channels using site-specific cysteine substitution. We found that intersubunit disulfide bonds can be formed between the A' helices in open channels, and that inducing disulfide bonds in most of the studied constructs resulted in potentiation of channel activation. This suggests that the A' helices of the C-linker regions are in close proximity when the channel is in the open state. Our finding is not compatible with a homology model of the CNGA1 C-linker made from the recently published X-ray crystallographic structure of the hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channel COOH terminus, and leads us to suggest that the C-linker region depicted in the crystal structure may represent the structure of the closed state. The opening conformational change would then involve a movement of the A' helices from a position parallel to the axis of the membrane to one perpendicular to the axis of the membrane. PMID:15738051

  1. Detection of a phosphorylated glycine-serine linker in an IgG-based fusion protein

    PubMed Central

    Tyshchuk, Oksana; Völger, Hans Rainer; Bulau, Patrick; Koll, Hans; Mølhøj, Michael

    2017-01-01

    ABSTRACT Molecular mass determination by electrospray ionization mass spectrometry of a recombinant IgG-based fusion protein (mAb1-F) produced in human embryonic kidney (HEK) cells demonstrated the presence of a dominant +79 Da product variant. Using LC-MS tryptic peptide mapping analysis and collision-induced dissociation (CID) and electron-transfer/higher-energy collision dissociation fragmentations, the modification was localized to the C-terminal serine residue of a glycine-serine linker [(G4S)2] of a fused heavy chain containing in total 2 (G4S)2-linkers. The modification was identified as a phosphorylation (+79.97 Da) by the presence of a 98 Da neutral loss reaction with CID, by spiking a synthetic phosphoserine peptide, and by dephosphorylation with alkaline phosphatase. A thermolysin digest combined with higher-energy collision dissociation (HCD) positioned the phosphoserine to one specific glycine-serine linker of the fused heavy chain, and the relative level of phosphorylated linker was determined to be 11.3% and 0.4% by LC-MS when the fusion protein was transiently expressed in HEK or in stably transformed Chinese hamster ovary cells, respectively. This observation demonstrates that fusions with glycine-serine linker sequences should be carefully evaluated during drug development to prevent the introduction of a phosphorylation site in therapeutic fusion proteins. PMID:27661266

  2. A multiscale model for simulating binding kinetics of proteins with flexible linkers.

    PubMed

    Chen, Jiawen; Xie, Zhong-Ru; Wu, Yinghao

    2014-10-01

    The kinetics of protein interactions are essential determinants in many cellular processes such as signal transduction and transcriptional regulation. Many proteins involved in these functions contain intrinsic disordered regions. This makes conformational flexibility become an unneglectable factor when studying the binding kinetic of these proteins. Compared with the binding of rigid proteins that is limited by diffusions, the binding mechanisms of proteins with internal flexibility are much more complicated. Using a small protein that contains two domains and a connecting loop as a testing system, we developed a multiscale simulation framework to study the role of flexible linkers in regulating kinetics of protein binding. The association and dissociation processes were implemented by a coarse-grained Monte-Carlo algorithm, while the conformational changes of the flexible linker were captured from all-atom molecular dynamic simulations. Our simulations illustrated that the presence of the extended domain linker can enhance the rate of protein association. On the other hand, the full-length flexible molecule is more difficult to dissociate than its two rigid domains but much easier than the molecule with a rigid linker. Overall, our studies demonstrated that both kinetics and thermodynamics of protein binding are closely modulated by the dynamic features of linker regions.

  3. A positive role for nucleosome mobility in the transcriptional activity of chromatin templates: restriction by linker histones.

    PubMed Central

    Ura, K; Hayes, J J; Wolffe, A P

    1995-01-01

    Nucleosome mobility facilitates the transcription of chromatin templates containing only histone octamers. Inclusion of linker histones in chromatin inhibits nucleosome mobility, directs nucleosome positioning and represses transcription. Transcriptional repression by linker histone occurs preferentially on templates associated with histone octamers relative to naked DNA. Mobile nucleosomes and the restriction of mobility by linker histones might be expected to exert a major influence on the accessibility of chromatin to regulatory molecules. Images PMID:7641694

  4. Linker length and flexibility induces new cellobiohydrolase activity of PoCel6A from Penicillium oxalicum.

    PubMed

    Gao, Le; Wang, Lushan; Jiang, Xukai; Qu, Yinbo

    2015-06-01

    In a previous study, a novel cellobiohydrolase, PoCel6A, with new enzymatic activity against p-nitrophenyl-β-D-cellobioside (pNPC), was purified from Penicillium oxalicum. The cellulose-binding module and catalytic domain of PoCel6A showed a high degree of sequence similarity with other fungal Cel6As. However, PoCel6A had 11 more amino acids in the linker region than other Cel6As. To evaluate the relationship between the longer linker of PoCel6A and its enzymatic activity, 11 amino acids were deleted from the linker region of PoCel6A. The shortened PoCel6A linker nullified the enzymatic activity against pNPC but dramatically increased the enzyme's capacity for crystalline cellulose degradation. The shortened linker segment appeared to have no effect on the secondary structural conformation of PoCel6A. Another variant (PoCel6A-6pro) with six consecutive proline residues in the interdomain linker had a higher rigid linker, and no enzymatic activity was observed against soluble and insoluble substrate. The flexibility of the linker had an important function in the formation of active cellulase. The length and flexibility of the linker is clearly able to modify the function of PoCel6A and induce new characteristics of Cel6A.

  5. Chaperone-Like Effect of the Linker on the Isolated C-Terminal Domain of Rabbit Muscle Creatine Kinase

    PubMed Central

    Chen, Zhe; Chen, Xiang-Jun; Xia, Mengdie; He, Hua-Wei; Wang, Sha; Liu, Huihui; Gong, Haipeng; Yan, Yong-Bin

    2012-01-01

    Intramolecular chaperones (IMCs), which are specific domains/segments encoded in the primary structure of proteins, exhibit chaperone-like activity against the aggregation of the other domains in the same molecule. In this research, we found that the truncation of the linker greatly promoted the thermal aggregation of the isolated C-terminal domain (CTD) of rabbit muscle creatine kinase (RMCK). Either the existence of the linker covalently linked to CTD or the supply of the synthetic linker peptide additionally could successfully protect the CTD of RMCK against aggregation in a concentration-dependent manner. Truncated fragments of the linker also behaved as a chaperone-like effect with lower efficiency, revealing the importance of its C-terminal half in the IMC function of the linker. The aggregation sites in the CTD of RMCK were identified by molecular dynamics simulations. Mutational analysis of the three key hydrophobic residues resulted in opposing effects on the thermal aggregation between the CTD with intact or partial linker, confirming the role of linker as a lid to protect the hydrophobic residues against exposure to solvent. These observations suggested that the linkers in multidomain proteins could act as IMCs to facilitate the correct folding of the aggregation-prone domains. Furthermore, the intactness of the IMC linker after proteolysis modulates the production of off-pathway aggregates, which may be important to the onset of some diseases caused by the toxic effects of aggregated proteolytic fragments. PMID:22947872

  6. A linker peptide with high affinity towards silica-containing materials.

    PubMed

    Sunna, Anwar; Chi, Fei; Bergquist, Peter L

    2013-06-25

    A peptide sequence with affinity to silica-containing materials was fused to a truncated form of Streptococcus strain G148 Protein G. The resulting recombinant Linker-Protein G (LPG) was produced in Escherichia coli and purified to apparent homogeneity. It displayed high affinity towards two natural clinoptilolite zeolites. The LPG also displayed high binding affinity towards commercial-grade synthetic zeolite, silica and silica-containing materials. A commercial sample of the truncated Protein G and a basic protein, both without the linker, did not bind to natural or synthetic zeolites or silica. We conclude that the zeolite-binding affinity is mediated by the linker peptide sequence. As a consequence, these data may imply that the binding affinity is directed to the SiO2 component rather than to the atomic orientation on the zeolite crystal surface as previously assumed.

  7. Development of a Multifunctional Benzophenone Linker for Peptide Stapling and Photoaffinity Labelling.

    PubMed

    Wu, Yuteng; Olsen, Lasse B; Lau, Yu Heng; Jensen, Claus Hatt; Rossmann, Maxim; Baker, Ysobel R; Sore, Hannah F; Collins, Súil; Spring, David R

    2016-04-15

    Photoaffinity labelling is a useful method for studying how proteins interact with ligands and biomolecules, and can help identify and characterise new targets for the development of new therapeutics. We present the design and synthesis of a novel multifunctional benzophenone linker that serves as both a photo-crosslinking motif and a peptide stapling reagent. Using double-click stapling, we attached the benzophenone to the peptide via the staple linker, rather than by modifying the peptide sequence with a photo-crosslinking amino acid. When applied to a p53-derived peptide, the resulting photoreactive stapled peptide was able to preferentially crosslink with MDM2 in the presence of competing protein. This multifunctional linker also features an extra alkyne handle for downstream applications such as pull-down assays, and can be used to investigate the target selectivity of stapled peptides.

  8. Thermosensitivity of N-isopropylacrylamide hydrogels cross-linked with degradable cross-linker.

    PubMed

    Pérez, Paloma; Gallardo, Alberto; Corrigan, Owen I; Román, Julio San

    2008-01-01

    Thermosensitive N-isopropylacrylamide (NIPA)-based hydrogels have been prepared using a biodegradable pseudo-peptide (DMTLT, a tri-molecular adduct of tyrosine, lysine, tyrosine) as cross-linker. This new cross-linker provides a similar cross-linking efficiency as N,N' methylenbisacrylamide (BIS) (a standard biostable cross-linker) used as reference. The amount of DMTLT has shown to modulate, in addition to the cross-linking density, the transition temperature (the higher the amount of DMTLT, the lower the transition temperature), as well as the morphology and the whole aqueous behaviour. The incorporation of hydrophilic N,N'-dimethylacrylamide (DMA) increases the transition temperature, as expected. Finally, the matrices have exhibited in aqueous media a well-defined pulsatile behaviour in swelling and release of benzoic acid and dextran as models of ionisable molecules and non-ionisable macromolecules.

  9. Wheat Gluten Blends with Maleic Anhydride-Functionalized Polyacrylate Cross-Linkers for Improved Properties.

    PubMed

    Diao, Cheng; Xia, Hongwei; Parnas, Richard S

    2015-10-14

    A family of polyacrylate-based cross-linkers was synthesized to maximize the toughness of high Tg, high modulus wheat gluten blends in the glassy state. Mechanical testing and damping measurements were conducted to provide an example where the work of fracture and strength of the blend substantially exceeds polystyrene while maintaining flexure stiffness in excess of 3 GPa. The new rubbery cross-linkers, polymethyl acrylate-co-maleic anhydride and polyethyl acrylate-co-maleic anhydride, improve WG mechanical properties and reduce water absorption simultaneously. MDSC, FTIR, HPLC, and NMR data confirmed the cross-linking reaction with wheat gluten. Flexural, DMA, and water absorption testing were carried out to characterize the property improvements. DMA was conducted to investigate the relationship between energy damping and mechanical property improvement. If the cross-linker damping temperature is close to the testing temperature, the entire sample exhibits high damping, toughness, and strength.

  10. Development of a Multifunctional Benzophenone Linker for Peptide Stapling and Photoaffinity Labelling

    PubMed Central

    Wu, Yuteng; Olsen, Lasse B.; Lau, Yu Heng; Jensen, Claus Hatt; Rossmann, Maxim; Baker, Ysobel R.; Sore, Hannah F.; Collins, Súil

    2016-01-01

    Abstract Photoaffinity labelling is a useful method for studying how proteins interact with ligands and biomolecules, and can help identify and characterise new targets for the development of new therapeutics. We present the design and synthesis of a novel multifunctional benzophenone linker that serves as both a photo‐crosslinking motif and a peptide stapling reagent. Using double‐click stapling, we attached the benzophenone to the peptide via the staple linker, rather than by modifying the peptide sequence with a photo‐crosslinking amino acid. When applied to a p53‐derived peptide, the resulting photoreactive stapled peptide was able to preferentially crosslink with MDM2 in the presence of competing protein. This multifunctional linker also features an extra alkyne handle for downstream applications such as pull‐down assays, and can be used to investigate the target selectivity of stapled peptides. PMID:26919579

  11. Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs

    PubMed Central

    Klinkebiel, Arne; Beyer, Ole; Malawko, Barbara

    2016-01-01

    New triazine-based tricarboxylic acid linkers were prepared as elongated relatives of triazinetribenzoic acid (TATB). Additionally, functional groups (NO2, NH2, OMe, OH) were introduced for potential post-synthetic modification (PSM) of MOFs. Functionalized tris(4-bromoaryl)triazine “cores” (3a,3b) were obtained by unsymmetric trimerization mixing one equivalent of an acid chloride (OMe or NO2 substituted) with two equivalents of an unsubstituted nitrile. Triple Suzuki coupling of the cores 3 with suitable phenyl- and biphenylboronic acid derivatives provided elongated tricarboxylic acid linkers as carboxylic acids 17 and 20 or their esters 16 and 19. Reduction of the nitro group and cleavage of the methoxy group gave the respective amino and hydroxy-substituted triazine linkers. PMID:28144293

  12. Enhanced tumor retention of radioiodinated anti-epidermal growth factor receptor antibody using novel bifunctional iodination linker for radioimmunotherapy

    PubMed Central

    KIM, EUN JUNG; KIM, BYOUNG SOO; CHOI, DAN BEE; CHI, SUNG-GIL; CHOI, TAE HYUN

    2016-01-01

    Radioimmunotherapy (RIT) uses an antibody labeled with a radionuclide to deliver cytotoxic radiation to a target tumor cells. Radioiodine is most commonly employed to prepare radiolabeled proteins (antibodies, peptides) for in vitro and in vivo applications. A major shortcoming of radioiodinated proteins prepared by direct labeling methods is their deiodination in vivo. For the preparation of more stable radioiodinated antibodies, we developed a new linker (N-(4-isothiocyanatobenzyl)-2-(3-(tributylstannyl)phenyl) acetamide (IBPA). This study evaluated the usefulness of IBPA as a linker for the stable radioiodinated internalizing antibody, cetuximab. Directly labeled cetuximab ([125I]-cetuximab) was prepared by the chloramine T method. To prepare indirectly labeled cetuximab using IBPA ([125I]-IBPA-cetuximab), IBPA was radioiodinated using chloramine-T to give N-(4-isothiocyanatobenzyl)-2-(3-[125I]phenyl)acetamide ([125I]-IBPA), which was purified by high performance liquid chromatography. [125I]-IBPA was then conjugated to cetuximab. In vitro target binding and internalizing assays were performed in PC9, LS174T, and FaDu cell lines. In vivo planar images were obtained using an Inveon SPECT scanner 3, 24, 48, and 168 h after i.v. injection of [125I]-cetuximab or [125I]-IBPA-cetuximab in athymic mice bearing LS174T tumor xenografts. Specific binding and internalized radioactivity of [125I]-IBPA-cetuximab were higher than those of [125I]-cetuximab in PC9, LS174T, and FaDu cell lines. In planar images scant radioactivity was evident in thyroid glands after injection of [125I]-IBPA-cetuximab, while a high level of radioactivity was present in thyroid glands after injection of [125I]-cetuximab. Tumor uptake value of [125I]-IBPA-cetuximab was higher than that of [125I]-cetuximab for up to 168 h. [125I]-IBPA-cetuximab is stable and resistant to deiodination in vivo. IBPA is a promising bi-functional linker for radioiodination of internalizing monoclonal antibodies for in

  13. Cell biology of Smad2/3 linker region phosphorylation in vascular smooth muscle.

    PubMed

    Rezaei, Hossein B; Kamato, Danielle; Ansari, Ghazaleh; Osman, Narin; Little, Peter J

    2012-08-01

    The transforming growth factor (TGF)-β superfamily of ligands regulates a diverse set of cellular functions. Transforming growth factor-β induces its biological effects through Type I and Type II transmembrane receptors that have serine/threonine kinase activities and weak tyrosine kinase activity. In vascular smooth muscle, TGF-β binds to the TGF-β Type II receptor (TβRII) at the cell surface, recruiting the Type I receptor (TβRI) to form a heterocomplex. Consequently, after phosphorylation and activation of TβRI, the transcription factors receptor activated (R-) Smad2 and Smad3 are recruited and activated through phosphorylation of C terminal residues. Overall, Smad2/3 and co-Smad4 have similar structures consisting of three regions an N-terminal MH1 domain, a C-terminal MH2 domain and a central linker region. Phosphorylation of the Smad linker region appears to have an important role in the regulation of Smad activity and function. The mitogen-activated protein kinase (MAPK) family, CDK2, CDK4 and calcium-calmodulin dependent kinase are the main kinases that phosphorylate sites in the linker region. The role of the linker region includes enabling the formation of Smad homo-oligomers and provision of phosphorylation sites for MAPK and other kinases. In some instances, linker region phosphorylation regulates the inhibition of the nuclear translocation of Smads. In the present review, we describe TGF-β signalling through Smad2/3 and the importance of the linker region in the regulation and expression of genes induced by TGF-β superfamily ligands in the context of vascular smooth muscle.

  14. The Centrosomal Linker and Microtubules Provide Dual Levels of Spatial Coordination of Centrosomes

    PubMed Central

    Panic, Marko; Hata, Shoji; Neuner, Annett; Schiebel, Elmar

    2015-01-01

    The centrosome is the principal microtubule organizing center in most animal cells. It consists of a pair of centrioles surrounded by pericentriolar material. The centrosome, like DNA, duplicates exactly once per cell cycle. During interphase duplicated centrosomes remain closely linked by a proteinaceous linker. This centrosomal linker is composed of rootletin filaments that are anchored to the centrioles via the protein C-Nap1. At the onset of mitosis the linker is dissolved by Nek2A kinase to support the formation of the bipolar mitotic spindle. The importance of the centrosomal linker for cell function during interphase awaits characterization. Here we assessed the phenotype of human RPE1 C-Nap1 knockout (KO) cells. The absence of the linker led to a modest increase in the average centrosome separation from 1 to 2.5 μm. This small impact on the degree of separation is indicative of a second level of spatial organization of centrosomes. Microtubule depolymerisation or stabilization in C-Nap1 KO cells dramatically increased the inter-centrosomal separation (> 8 μm). Thus, microtubules position centrosomes relatively close to one another in the absence of linker function. C-Nap1 KO cells had a Golgi organization defect with a two-fold expansion of the area occupied by the Golgi. When the centrosomes of C-Nap1 KO cells showed considerable separation, two spatially distinct Golgi stacks could be observed. Furthermore, migration of C-Nap1 KO cells was slower than their wild type RPE1 counterparts. These data show that the spatial organization of centrosomes is modulated by a combination of centrosomal cohesion and microtubule forces. Furthermore a modest increase in centrosome separation has major impact on Golgi organization and cell migration. PMID:26001056

  15. Ler interdomain linker is essential for anti-silencing activity in enteropathogenic Escherichia coli

    PubMed Central

    Mellies, Jay L.; Larabee, Fredrick J.; Zarr, Melissa A.; Horback, Katy L.; Lorenzen, Emily; Mavor, David

    2008-01-01

    Enteropathogenic Escherichia coli (EPEC) expresses a type III secretion system (T3SS) required for pathogenesis. Regulation of the genes encoding the T3SS is complex; two major regulators control transcription, the silencer H-NS, and the related H-NS-like protein Ler. Our laboratory is interested in understanding the molecular differences that distinguish the anti-silencer Ler from H-NS, and how Ler differentially regulates EPEC virulence genes. Here, we demonstrate that mutated Ler proteins either containing H-NS α-helices 1 and 2, missing from Ler, or truncated for the 11 aa C-terminal extension compared with the related H-NS protein, did not appreciably alter Ler function. In contrast, mutating the proline at position 92 of Ler, in the conserved C-terminal DNA binding motif, eliminated Ler activity. Inserting 11 H-NS-specific amino acids, 11 alanines or 6 alanines into the Ler linker severely impaired the ability of Ler to increase LEE5 transcription. To extend our analysis, we constructed six chimeric proteins containing the N terminus, linker region or C terminus of Ler in different combinations with the complementary domains of H-NS, and monitored their in vivo activities. Replacing the Ler linker domain with that of H-NS, or replacing the Ler C-terminal, DNA binding domain with that of H-NS eliminated the ability of Ler to increase transcription at the LEE5 promoter. Thus, the linker and C-terminal domains of Ler and H-NS are not functionally equivalent. Conversely, replacing the H-NS linker region with that of Ler caused increased transcription at LEE5 in a strain deleted for hns. In summary, the interdomain linker specific to Ler is necessary for anti-silencing activity in EPEC. PMID:19047730

  16. Boosted objects and jet substructure at the LHC: Report of BOOST2012, held at IFIC Valencia, 23rd-27th of July 2012

    SciTech Connect

    Altheimer, A.

    2014-03-21

    This report of the BOOST2012 workshop presents the results of four working groups that studied key aspects of jet substructure. We discuss the potential of first-principle QCD calculations to yield a precise description of the substructure of jets and study the accuracy of state-of-the-art Monte Carlo tools. Limitations of the experiments’ ability to resolve substructure are evaluated, with a focus on the impact of additional (pile-up) proton proton collisions on jet substructure performance in future LHC operating scenarios. The final section summarizes the lessons learnt from jet substructure analyses in searches for new physics in the production of boosted top quarks.

  17. Impact of metal-alkoxide functionalized linkers on H2 binding: A density functional study

    NASA Astrophysics Data System (ADS)

    Banu, Tahamida; Ghosh, Avik; Das, Abhijit K.

    2016-08-01

    The effect of metal-alkoxide functionalization of different organic linkers on the H2 binding is investigated employing DFT approach. While analyzing the H2 binding interaction of magnesium-alkoxide modified benzene, naphthalene, anthracene and pyrene linkers, we find their comparable affinity toward H2 molecules. Six-member alkoxide ring containing naphthalene and pyrene systems interact with the H2 molecules in a comparatively better way than their five-member analogues. AIM, NBO and LMO-EDA analyses have been performed to comprehend the bonding nature between Mg center and the H2 molecules. Polarization along with the charge transfer interactions play significant role in stabilizing the systems.

  18. Safety-catch linker strategies for the production of radiopharmaceuticals labeled with positron-emitting isotopes.

    PubMed

    Maclean, Derek; Zhu, Jiang; Chen, Mingying; Hale, Ron; Satymurthy, Nagichettiar; Barrio, Jorge R

    2003-08-27

    A novel synthetic stratetegy for compounds labeled with the positron-emitting isotope carbon-11 is described. The use of precursors attached to a solid support via safety-catch linkers allows selective release of radiolabeled material, leaving unreacted precursor attached to the support. Two different linkers demonstrate the application to the preparation of radiolabeled N-alkyl tertiary amines and N-alkylsulfonamides. This technique is expected to lead to more widespread use of positron emission tomography for the in vivo analysis of compound behavior.

  19. Preparation of bifunctional isocyanate hydroxamate linkers: Synthesis of carbamate and urea tethered polyhydroxamic acid chelators

    PubMed Central

    Fernando, Rasika; Shirley, Jonathan M.; Torres, Emilio; Jacobs, Hollie K.; Gopalan, Aravamudan S.

    2012-01-01

    Two novel bifunctional N-methylhydroxamate-isocyanate linkers 20 and 21 were prepared in good yield and high purity from the corresponding amine salts using a biphasic reaction with phosgene. The facile ring opening reaction of N-Boc lactams using the anion of O-benzylhydroxylamine gave the protected amino hydroxamates 6a and 6c in good yields. The selective methylation of the hydroxamate nitrogen in the presence of the N-Boc group in these intermediates could be readily accomplished. The utility of the linkers was clearly demonstrated by the synthesis of the carbamate-tethered trishydroxamic acid 27 and the urea-tethered 29 PMID:23162172

  20. Linear aliphatic dialkynes as alternative linkers for double-click stapling of p53-derived peptides.

    PubMed

    Lau, Yu Heng; de Andrade, Peterson; McKenzie, Grahame J; Venkitaraman, Ashok R; Spring, David R

    2014-12-15

    We investigated linear aliphatic dialkynes as a new structural class of i,i+7 linkers for the double-click stapling of p53-based peptides. The optimal combination of azido amino acids and dialkynyl linker length for MDM2 binding was determined. In a direct comparison between aliphatic and aromatic staple scaffolds, the aliphatic staples resulted in superior binding to MDM2 in vitro and superior p53-activating capability in cells when using a diazidopeptide derived from phage display. This work demonstrates that the nature of the staple scaffold is an important factor that can affect peptide bioactivity in cells.

  1. An intrinsically disordered linker plays a critical role in bacterial cell division.

    PubMed

    Buske, P J; Mittal, Anuradha; Pappu, Rohit V; Levin, Petra Anne

    2015-01-01

    In bacteria, animals, fungi, and many single celled eukaryotes, division is initiated by the formation of a ring of cytoskeletal protein at the nascent division site. In bacteria, the tubulin-like GTPase FtsZ serves as the foundation for the cytokinetic ring. A conserved feature of FtsZ is an intrinsically disordered peptide known as the C-terminal linker. Chimeric experiments suggest the linker acts as a flexible boom allowing FtsZ to associate with the membrane through a conserved C-terminal domain and also modulates interactions both between FtsZ subunits and between FtsZ and modulatory proteins in the cytoplasm.

  2. Improving solubilization in microemulsions with additives. 1. The lipophilic linker role

    SciTech Connect

    Graciaa, A.; Lachaise, J.; Cucuphat, C. ); Bourrel, M. ); Salager, J.L. )

    1993-03-01

    Very lipophilic additives are able to substantially improve the solubilization in surfactant-oil-water microemulsions. The so-called lipophilic linker effect is studied, and its role is discussed. It is shown that the presence of a very lipophilic amphiphilic additive may improve substantially the solubilization in microemulsions. This substance is called a lipophilic linker because its preferential orientation in the oil layers next to the interface might provide some ordering of the oil molecules as well as an additional link with the surfactant. Both effects result in a higher interaction on the oil side of the interface. 21 refs., 5 figs., 1 tab.

  3. Improving corrosion resistance of post-tensioned substructures emphasizing high performance grouts

    NASA Astrophysics Data System (ADS)

    Schokker, Andrea Jeanne

    The use of post-tensioning in bridges can provide durability and structural benefits to the system while expediting the construction process. When post-tensioning is combined with precast elements, traffic interference can be greatly reduced through rapid construction. Post-tensioned concrete substructure elements such as bridge piers, hammerhead bents, and straddle bents have become more prevalent in recent years. Chloride induced corrosion of steel in concrete is one of the most costly forms of corrosion each year. Coastal substructure elements are exposed to seawater by immersion or spray, and inland bridges may also be at risk due to the application of deicing salts. Corrosion protection of the post-tensioning system is vital to the integrity of the structure because loss of post-tensioning can result in catastrophic failure. Documentation for durability design of the grout, ducts, and anchorage systems is very limited. The objective of this research is to evaluate the effectiveness of corrosion protection measures for post-tensioned concrete substructures by designing and testing specimens representative of typical substructure elements using state-of-the-art practices in aggressive chloride exposure environments. This was accomplished through exposure testing of twenty-seven large-scale beam specimens and ten large-scale column specimens. High performance grout for post-tensioning tendon injection was also developed through a series of fresh property tests, accelerated exposure tests, and a large-scale pumping test to simulate field conditions. A high performance fly ash grout was developed for applications with small vertical rises, and a high performance anti-bleed grout was developed for applications involving large vertical rises such as tall bridge piers. Long-term exposure testing of the beam and column specimens is ongoing, but preliminary findings indicate increased corrosion protection with increasing levels of post-tensioning, although traditional

  4. Common cold

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000678.htm Common cold To use the sharing features on this page, please enable JavaScript. The common cold most often causes a runny nose, nasal congestion, ...

  5. A SUBSTRUCTURE INSIDE SPIRAL ARMS, AND A MIRROR IMAGE ACROSS THE GALACTIC MERIDIAN

    SciTech Connect

    Vallée, Jacques P.

    2016-04-10

    Though the galactic density wave theory is over 50 years old and is well known in science, it has been difficult to say whether it fits our own Milky Way disk. Here we show a substructure inside the spiral arms. This substructure is reversing with respect to the Galactic Meridian (longitude zero), and crosscuts of the arms at negative longitudes appear as mirror images of crosscuts of the arms at positive longitudes. Four lanes are delineated: a mid-arm (extended {sup 12}CO gas at the mid-arm, H i atoms), an in-between offset by about 100 pc (synchrotron, radio recombination lines), an in-between offset by about 200 pc (masers, colder dust), and an inner edge (hotter dust seen in mid-IR and near-IR)

  6. Interference substructure of above-threshold ionization peaks in the stabilization regime

    NASA Astrophysics Data System (ADS)

    Toyota, Koudai; Tolstikhin, Oleg I.; Morishita, Toru; Watanabe, Shinichi

    2008-09-01

    The photoelectron spectra produced in the photodetachment of H- (treated in the single-active-electron approximation) by strong high-frequency laser pulses with adequately chosen laser parameters in the stabilization regime are theoretically studied for elliptic polarization over an extended parameter range. An oscillating substructure in the above-threshold ionization peaks is observed, which confirms similar findings in the one-dimensional (1D) [K. Toyota , Phys. Rev. A 76, 043418 (2007)] and 3D calculations for linear polarization [O. I. Tolstikhin, Phys. Rev. A 77, 032712 (2008)]. The mechanism is an interference between the photoelectron wave packets created in the rising and falling parts of the pulse which is specific to the stabilization regime. We thus conclude that this interference substructure is robust for any polarization and over a wide range of the laser parameters, and hence should be observable experimentally.

  7. Twisting phonons in complex crystals with quasi-one-dimensional substructures.

    PubMed

    Chen, Xi; Weathers, Annie; Carrete, Jesús; Mukhopadhyay, Saikat; Delaire, Olivier; Stewart, Derek A; Mingo, Natalio; Girard, Steven N; Ma, Jie; Abernathy, Douglas L; Yan, Jiaqiang; Sheshka, Raman; Sellan, Daniel P; Meng, Fei; Jin, Song; Zhou, Jianshi; Shi, Li

    2015-04-15

    A variety of crystals contain quasi-one-dimensional substructures, which yield distinctive electronic, spintronic, optical and thermoelectric properties. There is a lack of understanding of the lattice dynamics that influences the properties of such complex crystals. Here we employ inelastic neutron scatting measurements and density functional theory calculations to show that numerous low-energy optical vibrational modes exist in higher manganese silicides, an example of such crystals. These optical modes, including unusually low-frequency twisting motions of the Si ladders inside the Mn chimneys, provide a large phase space for scattering acoustic phonons. A hybrid phonon and diffuson model is proposed to explain the low and anisotropic thermal conductivity of higher manganese silicides and to evaluate nanostructuring as an approach to further suppress the thermal conductivity and enhance the thermoelectric energy conversion efficiency. This discovery offers new insights into the structure-property relationships of a broad class of materials with quasi-one-dimensional substructures for various applications.

  8. Characterization Method for 3D Substructure of Nuclear Cell Based on Orthogonal Phase Images

    PubMed Central

    Ji, Ying; Liang, Minjie; Hua, Tingting; Xu, Yuanyuan; Xin, Zhiduo; Wang, Yawei

    2015-01-01

    A set of optical models associated with blood cells are introduced in this paper. All of these models are made up of different parts possessing symmetries. The wrapped phase images as well as the unwrapped ones from two orthogonal directions related to some of these models are obtained by simulation technique. Because the phase mutation occurs on the boundary between nucleus and cytoplasm as well as on the boundary between cytoplasm and environment medium, the equation of inflexion curve is introduced to describe the size, morphology, and substructure of the nuclear cell based on the analysis of the phase features of the model. Furthermore, a mononuclear cell model is discussed as an example to verify this method. The simulation result shows that characterization with inflexion curve based on orthogonal phase images could describe the substructure of the cells availably, which may provide a new way to identify the typical biological cells quickly without scanning. PMID:26355740

  9. Mechanical properties of the hierarchical honeycombs with stochastic Voronoi sub-structures

    NASA Astrophysics Data System (ADS)

    Du, Yinghong; Pugno, Nicola; Gong, Baoming; Wang, Dongpo; Sun, Yongtao; Ding, Qian

    2015-09-01

    The introduction of hierarchy into structures has been credited with changing mechanical properties. In this study, periodically hierarchical honeycomb with irregular sub-structure cells has been designed based on the Voronoi tessellation algorithm. Numerical investigation has been performed to determine the influence of structural hierarchy and irregularity on the in-plane elastic properties. Irregular hierarchical honeycombs can be up to 3 times stiffer than regular hexagonal honeycombs on an equal density basis. Both the stiffness and Poisson's ratio of the hierarchical honeycomb are insensitive to the degree of regularity, and depend on the cell-wall thickness-to-length ratio of the super-structure. Increasing the relative lengths of the super- and sub-structures results in the increment of Young's modulus, whereas Poisson's ratio almost remains constant varying from 1.0 to 0.7.

  10. Dislocation substructures and nonproportional hardening. [TEM observations under tension-torsion cyclic loading

    SciTech Connect

    Shiinghwa Doong; Socie, D.F.; Robertson, I.M. )

    1990-10-01

    The dislocation substructures created in 1100 aluminum, OFHC copper, and type 304 and 310 stainless steels by in-phase (proportional) and 90 deg out-of-phase (nonproportional) tension-torsion cyclic loading were examined with a transmission-electron microscope. Multislip structures (cells and subgrains) are observed in aluminum under both in-phase and 90 deg out-of-phase tension-torsion loading. For copper and stainless steel, single-slip structures (planar dislocations, matrix veins, and ladders) are observed after proportional loading, whereas multislip structures (cells and labyrinths) are observed after nonproportional loading. The increased cyclic hardening of copper and stainless steels under nonproportional loading is attributed to the change of dislocation substructures. Based on these observations, formulation of a nonproportionality parameter for constitutive modeling is discussed.

  11. Serous cutaneous glands in anurans: Fourier transform analysis of the repeating secretory granule substructure

    NASA Astrophysics Data System (ADS)

    Nosi, D.; Delfino, G.; Quercioli, F.

    2013-03-01

    A combined transmission electron microscopy (TEM) and Fourier transform analysis has been performed on the secretory granules storing active peptides/proteins in serous cutaneous glands of n = 12 anuran species. Previous TEM investigation showed that the granules are provided with remarkable repeating substructures based on discrete subunits, arranged into a consistent framework. Furthermore, TEM findings revealed that this recurrent arrangement is acquired during a prolonged post-Golgian (or maturational) processing that affects the secretory product. Maturation leads to a variety of patterns depending on the degree of subunit clustering. This variety of recurrent patterns has been plotted into a range of frequency spectra. Through this quantitative approach, we found that the varying granule substructure can be reduced to a single mechanism of peptide/protein aggregation.

  12. Visualization of podocyte substructure with structured illumination microscopy (SIM): a new approach to nephrotic disease

    PubMed Central

    Pullman, James M.; Nylk, Jonathan; Campbell, Elaine C.; Gunn-Moore, Frank J.; Prystowsky, Michael B.; Dholakia, Kishan

    2016-01-01

    A detailed microscopic analysis of renal podocyte substructure is essential to understand and diagnose nephrotic kidney disease. Currently only time consuming electron microscopy (EM) can resolve this substructure. We used structured illumination microscopy (SIM) to examine frozen sections of renal biopsies stained with an immunofluorescence marker for podocin, a protein localized to the perimeter of the podocyte foot processes and compared them with EM in both normal and nephrotic disease biopsies. SIM images of normal glomeruli revealed curvilinear patterns of podocin densely covering capillary walls similar to podocyte foot processes seen by EM. Podocin staining of all nephrotic disease biopsies were significantly different than normal, corresponding to and better visualizing effaced foot processes seen by EM. The findings support the first potential use of SIM in the diagnosis of nephrotic disease. PMID:26977341

  13. Development and Demonstration of a Magnesium-Intensive Vehicle Front-End Substructure

    SciTech Connect

    Logan, Stephen D.; Forsmark, Joy H.; Osborne, Richard

    2016-07-01

    This project is the final phase (designated Phase III) of an extensive, nine-year effort with the objectives of developing a knowledge base and enabling technologies for the design, fabrication and performance evaluation of magnesium-intensive automotive front-end substructures intended to partially or completely replace all-steel comparators, providing a weight savings approaching 50% of the baseline. Benefits of extensive vehicle weight reduction in terms of fuel economy increase, extended vehicle range, vehicle performance and commensurate reductions in greenhouse gas emissions are well known. An exemplary vehicle substructure considered by the project is illustrated in Figure 1, along with the exterior vehicle appearance. This unibody front-end “substructure” is one physical objective of the ultimate design and engineering aspects established at the outset of the larger collective effort.

  14. Discovering Concept Mappings by Similarity Propagation among Substructures

    NASA Astrophysics Data System (ADS)

    Pan, Qi H.; Hadzic, Fedja; Dillon, Tharam S.

    Concept matching is important when heterogeneous data sources are to be merged for the purpose of knowledge sharing. It has many useful applications in areas such as schema matching, ontology matching, scientific knowledge management, e-commerce, enterprise application integration, etc. With the desire of knowledge sharing and reuse in these fields, merging commonly occurs among different organizations where the knowledge describing the same domain is to be matched. Due to the different naming conventions, granularity and the use of concepts in different contexts, a semantic approach to this problem is preferred in comparison to syntactic approach that performs matches based upon the labels only. We propose a concept matching method that initially does not consider labels when forming candidate matches, but rather utilizes structural information to take the context into account and detect complex matches. Real world knowledge representations (schemas) are used to evaluate the method.

  15. Human linker histones: interplay between phosphorylation and O-β-GlcNAc to mediate chromatin structural modifications

    PubMed Central

    2011-01-01

    Eukaryotic chromatin is a combination of DNA and histone proteins. It is established fact that epigenetic mechanisms are associated with DNA and histones. Initial studies emphasize on core histones association with DNA, however later studies prove the importance of linker histone H1 epigenetic. There are many types of linker histone H1 found in mammals. These subtypes are cell specific and their amount in different types of cells varies as the cell functions. Many types of post-translational modifications which occur on different residues in each subtype of linker histone H1 induce conformational changes and allow the different subtypes of linker histone H1 to interact with chromatin at different stages during cell cycle which results in the regulation of transcription and gene expression. Proposed O-glycosylation of linker histone H1 promotes condensation of chromatin while phosphorylation of linker histone H1 is known to activate transcription and gene regulation by decondensation of chromatin. Interplay between phosphorylation and O-β-GlcNAc modification on Ser and Thr residues in each subtype of linker histone H1 in Homo sapiens during cell cycle may result in diverse functional regulation of proteins. This in silico study describes the potential phosphorylation, o-glycosylation and their possible interplay sites on conserved Ser/Thr residues in various subtypes of linker histone H1 in Homo sapiens. PMID:21749719

  16. General approach for introduction of various chemical labels in specific RNA locations based on insertion of amino linkers.

    PubMed

    Graifer, Dmitri; Karpova, Galina

    2013-11-25

    Introduction of reporter groups at designed RNA sites is a widely accepted approach to gain information about the molecular environment of RNAs in their complexes with other biopolymers formed during various cellular processes. A general approach to obtain RNAs bearing diverse reporter groups at designed locations is based on site-specific insertion of groups containing primary aliphatic amine functions (amino linkers) with their subsequent selective derivatization by appropriate chemicals. This article is a brief review on methods for site-specific introduction of amino linkers in different RNAs. These methods comprise: (i) incorporation of a nucleoside carrying an amino-linker or a function that can be substituted with it into oligoribonucleotides in the course of their chemical synthesis; (ii) assembly of amino linker-containing RNAs from short synthetic fragments via their ligation; (iii) synthesis of amino linker-modified RNAs using T7 RNA polymerase; (iv) insertion of amino linkers into unmodified RNAs at functional groups of a certain type such as the 5'-phosphates and N7 of guanosine residues and (v) introduction of an amino linker into long highly structured RNAs exploiting an approach based on sequence-specific modification of nucleic acids. Particular reporter groups used for derivatization of amino linker-containing RNAs together with types of RNA derivatives obtained and fields of their application are presented.

  17. Kilobase Pair Chromatin Fiber Contacts Promoted by Living-System-Like DNA Linker Length Distributions and Nucleosome Depletion.

    PubMed

    Bascom, Gavin D; Kim, Taejin; Schlick, Tamar

    2017-03-31

    Nucleosome placement, or DNA linker length patterns, are believed to yield specific spatial features in chromatin fibers, but details are unknown. Here we examine by mesoscale modeling how kilobase (kb) range contacts and fiber looping depend on linker lengths ranging from 18 to 45 bp, with values modeled after living systems, including nucleosome free regions (NFRs) and gene encoding segments. We also compare artificial constructs with alternating versus randomly distributed linker lengths in the range of 18-72 bp. We show that nonuniform distributions with NFRs enhance flexibility and encourage kb-range contacts. NFRs between neighboring gene segments diminish short-range contacts between flanking nucleosomes, while enhancing kb-range contacts via hierarchical looping. We also demonstrate that variances in linker lengths enhance such contacts. In particular, moderate sized variations in fiber linker lengths (∼27 bp) encourage long-range contacts in randomly distributed linker length fibers. Our work underscores the importance of linker length patterns, alongside bound proteins, in biological regulation. Contacts formed by kb-range chromatin folding are crucial to gene activity. Because we find that special linker length distributions in living systems promote kb contacts, our work suggests ways to manipulate these patterns for regulation of gene activity.

  18. A dramatic synergistic effect of a flexible achiral linker on a rigid chiral cis-1,2-diamine bifunctional organocatalyst.

    PubMed

    Matsunaga, Hirofumi; Tajima, Daisuke; Kawauchi, Tetsuro; Yasuyama, Takuro; Ando, Shin; Ishizuka, Tadao

    2017-04-05

    The combination of a "rigid" chiral bicyclic cis-1,2-diamine skeleton with steric bulkiness and a "flexible" achiral linker was newly designed as a bifunctional organocatalyst framework and it showed excellent catalytic activity of up to 0.05 mol%, accompanied by the reversal of enantioselection depending on the position of the linker, in an amine-thiourea organocatalyzed asymmetric Michael reaction.

  19. Analysis of East Asia Genetic Substructure Using Genome-Wide SNP Arrays

    PubMed Central

    Tian, Chao; Kosoy, Roman; Lee, Annette; Ransom, Michael; Belmont, John W.; Gregersen, Peter K.; Seldin, Michael F.

    2008-01-01

    Accounting for population genetic substructure is important in reducing type 1 errors in genetic studies of complex disease. As efforts to understand complex genetic disease are expanded to different continental populations the understanding of genetic substructure within these continents will be useful in design and execution of association tests. In this study, population differentiation (Fst) and Principal Components Analyses (PCA) are examined using >200 K genotypes from multiple populations of East Asian ancestry. The population groups included those from the Human Genome Diversity Panel [Cambodian, Yi, Daur, Mongolian, Lahu, Dai, Hezhen, Miaozu, Naxi, Oroqen, She, Tu, Tujia, Naxi, Xibo, and Yakut], HapMap [ Han Chinese (CHB) and Japanese (JPT)], and East Asian or East Asian American subjects of Vietnamese, Korean, Filipino and Chinese ancestry. Paired Fst (Wei and Cockerham) showed close relationships between CHB and several large East Asian population groups (CHB/Korean, 0.0019; CHB/JPT, 00651; CHB/Vietnamese, 0.0065) with larger separation with Filipino (CHB/Filipino, 0.014). Low levels of differentiation were also observed between Dai and Vietnamese (0.0045) and between Vietnamese and Cambodian (0.0062). Similarly, small Fst's were observed among different presumed Han Chinese populations originating in different regions of mainland of China and Taiwan (Fst's <0.0025 with CHB). For PCA, the first two PC's showed a pattern of relationships that closely followed the geographic distribution of the different East Asian populations. PCA showed substructure both between different East Asian groups and within the Han Chinese population. These studies have also identified a subset of East Asian substructure ancestry informative markers (EASTASAIMS) that may be useful for future complex genetic disease association studies in reducing type 1 errors and in identifying homogeneous groups that may increase the power of such studies. PMID:19057645

  20. Detection of Lensing Substructure Using Alma Observations of the Dusty Galaxy SDP.81

    DOE PAGES

    Hezaveh, Yashar D.; Dalal, Neal; Marrone, Daniel P.; ...

    2016-05-19

    We study the abundance of substructure in the matter density near galaxies using ALMA Science Verification observations of the strong lensing system SDP.81. We present a method to measure the abundance of subhalos around galaxies using interferometric observations of gravitational lenses. Using simulated ALMA observations we explore the effects of various systematics, including antenna phase errors and source priors, and show how such errors may be measured or marginalized. We apply our formalism to ALMA observations of SDP.81. We find evidence for the presence of a M = 108.96±0.12 M⊙ subhalo near one of the images, with a significance ofmore » 6.9σ in a joint fit to data from bands 6 and 7; the effect of the subhalo is also detected in both bands individually. We also derive constraints on the abundance of dark matter (DM) subhalos down to M ~ 2 × 107 M⊙, pushing down to the mass regime of the smallest detected satellites in the Local Group, where there are significant discrepancies between the observed population of luminous galaxies and predicted DM subhalos. We find hints of additional substructure, warranting further study using the full SDP.81 data set (including, for example, the spectroscopic imaging of the lensed carbon monoxide emission). We compare the results of this search to the predictions of ΛCDM halos, and find that given current uncertainties in the host halo properties of SDP.81, our measurements of substructure are consistent with theoretical expectations. Finally, observations of larger samples of gravitational lenses with ALMA should be able to improve the constraints on the abundance of galactic substructure.« less

  1. Thinking outside the ROCs: Designing Decorrelated Taggers (DDT) for jet substructure

    NASA Astrophysics Data System (ADS)

    Dolen, James; Harris, Philip; Marzani, Simone; Rappoccio, Salvatore; Tran, Nhan

    2016-05-01

    We explore the scale-dependence and correlations of jet substructure observables to improve upon existing techniques in the identification of highly Lorentz-boosted objects. Modified observables are designed to remove correlations from existing theoretically well-understood observables, providing practical advantages for experimental measurements and searches for new phenomena. We study such observables in W jet tagging and provide recommendations for observables based on considerations beyond signal and background efficiencies.

  2. Thinking outside the ROCs: Designing decorrelated taggers (DDT) for jet substructure

    SciTech Connect

    Dolen, James; Harris, Philip; Marzani, Simone; Rappoccio, Salvatore; Tran, Nhan

    2016-05-26

    Here, we explore the scale-dependence and correlations of jet substructure observables to improve upon existing techniques in the identification of highly Lorentz-boosted objects. Modified observables are designed to remove correlations from existing theoretically well-understood observables, providing practical advantages for experimental measurements and searches for new phenomena. We study such observables in W jet tagging and provide recommendations for observables based on considerations beyond signal and background efficiencies.

  3. Detection of Lensing Substructure Using Alma Observations of the Dusty Galaxy SDP.81

    SciTech Connect

    Hezaveh, Yashar D.; Dalal, Neal; Marrone, Daniel P.; Mao, Yao-Yuan; Morningstar, Warren; Wen, Di; Blandford, Roger D.; Carlstrom, John E.; Fassnacht, Christopher D.; Holder, Gilbert P.; Kemball, Athol; Marshall, Philip J.; Murray, Norman; Levasseur, Laurence Perreault; Vieira, Joaquin D.; Wechsler, Risa H.

    2016-05-19

    We study the abundance of substructure in the matter density near galaxies using ALMA Science Verification observations of the strong lensing system SDP.81. We present a method to measure the abundance of subhalos around galaxies using interferometric observations of gravitational lenses. Using simulated ALMA observations we explore the effects of various systematics, including antenna phase errors and source priors, and show how such errors may be measured or marginalized. We apply our formalism to ALMA observations of SDP.81. We find evidence for the presence of a M = 108.96±0.12 M subhalo near one of the images, with a significance of 6.9σ in a joint fit to data from bands 6 and 7; the effect of the subhalo is also detected in both bands individually. We also derive constraints on the abundance of dark matter (DM) subhalos down to M ~ 2 × 107 M, pushing down to the mass regime of the smallest detected satellites in the Local Group, where there are significant discrepancies between the observed population of luminous galaxies and predicted DM subhalos. We find hints of additional substructure, warranting further study using the full SDP.81 data set (including, for example, the spectroscopic imaging of the lensed carbon monoxide emission). We compare the results of this search to the predictions of ΛCDM halos, and find that given current uncertainties in the host halo properties of SDP.81, our measurements of substructure are consistent with theoretical expectations. Finally, observations of larger samples of gravitational lenses with ALMA should be able to improve the constraints on the abundance of galactic substructure.

  4. Vibrational Energy Flow Analysis Using a Substructure Approach: the Application of Receptance Theory to Fea and Sea

    NASA Astrophysics Data System (ADS)

    Shankar, K.; Keane, A. J.

    1997-04-01

    A method for studying the vibrational energy flows through structures based on receptance theory is presented. The structures are considered to be made up of subsystems, which may, in turn, be substructures modelled by using finite element analysis (FEA), each having been separately analyzed for its eigenvalues and eigenvectors. The method may be classified as a form of substructuring using free{puen}free interface conditions. It differs significantly from traditional substructuring in its use of matrices composed of the substructure Green functions, evaluated as summations over their uncoupled modes, to obtain the displacement contributions of the external and boundary coupling forces; also, the method can readily take into account variations in substructure damping. The proposed method can readily take into account variations in substructure damping. The proposed method additionally calculates the time averaged substructure vibrational energy levels by evaluating the balance between input and dissipated energies and the energy transfers through coupling nodes. It is therefore of particular interest when using FEA substructures to carry out statistical energy analysis (SEA) studies, since the resulting energy data can be readily applied to evaluate SEA parameters such as coupling loss factors.The formulation developed has been implemented as a computer program which uses substructure modal information from a commercial FEA package and then combines this to predict the response of the global model. Two simple examples involving two- and three-dimensional FEA models built from beam elements are presented, which show that there is good agreement between the substructure based predictions and the equivalent global models. Moreover, the method presented is computationally more efficient than using global FEA models, even when all the substructure modes are used. The method is then applied to study the SEA coupling loss factors of two further example structures: first

  5. Technology Transfer and Utilization Methodology; Further Analysis of the Linker Concept.

    ERIC Educational Resources Information Center

    Jolly, James A.; Creighton, J. W.

    This study is based on a comparison of data from two independent studies of technology utilization and dissemination methodology that sought to identify the behavior characteristics of "linkers" and "stabilizers" and their relative existence within different groups of technical personnel. Hypothesis for this study is that the…

  6. Assembly of bipolar microtubule structures by passive cross-linkers and molecular motors.

    PubMed

    Johann, D; Goswami, D; Kruse, K

    2016-06-01

    During cell division, sister chromatids are segregated by the mitotic spindle, a bipolar assembly of interdigitating antiparallel polar filaments called microtubules. The spindle contains the midzone, a stable region of overlapping antiparallel microtubules, that is essential for maintaining bipolarity. Although a lot is known about the molecular players involved, the mechanism underlying midzone formation and maintenance is still poorly understood. We study the interaction of polar filaments that are cross-linked by molecular motors moving directionally and by passive cross-linkers diffusing along microtubules. Using a particle-based stochastic model, we find that the interplay of motors and passive cross-linkers can generate a stable finite overlap between a pair of antiparallel polar filaments. We develop a mean-field theory to study this mechanism in detail and investigate the influence of steric interactions between motors and passive cross-linkers on the overlap dynamics. In the presence of interspecies steric interactions, passive cross-linkers mimic the behavior of molecular motors and stable finite overlaps are generated even for non-cross-linking motors. Finally, we develop a mean-field theory for a bundle of aligned polar filaments and show that they can self-organize into a spindlelike pattern. Our work suggests possible ways as to how cells can generate spindle midzones and control their extensions.

  7. Orientation of nucleosomes and linker DNA in calf thymus chromatin determined by photochemical dichroism

    NASA Astrophysics Data System (ADS)

    Mitra, Sekhar; Sen, Dipankar; Crothers, Donald M.

    1984-03-01

    The dichroism for photochemical attachment of a psoralen derivative to Mg2+ -stabilized chromatin fibres is used to deduce the orientation of nucleosomal disks and linker DNA in the 30-nm fibre. The new technique of photochemical electric dichroism should have general applicability to problems of nucleic acid organization in cellular subunits and viruses.

  8. Loop-length-dependent SVM prediction of domain linkers for high-throughput structural proteomics.

    PubMed

    Ebina, Teppei; Toh, Hiroyuki; Kuroda, Yutaka

    2009-01-01

    The prediction of structural domains in novel protein sequences is becoming of practical importance. One important area of application is the development of computer-aided techniques for identifying, at a low cost, novel protein domain targets for large-scale functional and structural proteomics. Here, we report a loop-length-dependent support vector machine (SVM) prediction of domain linkers, which are loops separating two structural domains. (DLP-SVM is freely available at: http://www.tuat.ac.jp/ approximately domserv/cgi-bin/DLP-SVM.cgi.) We constructed three loop-length-dependent SVM predictors of domain linkers (SVM-All, SVM-Long and SVM-Short), and also built SVM-Joint, which combines the results of SVM-Short and SVM-Long into a single consolidated prediction. The performances of SVM-Joint were, in most aspects, the highest, with a sensitivity of 59.7% and a specificity of 43.6%, which indicated that the specificity and the sensitivity were improved by over 2 and 3% respectively, when loop-length-dependent characteristics were taken into account. Furthermore, the sensitivity and specificity of SVM-Joint were, respectively, 37.6 and 17.4% higher than those of a random guess, and also superior to those of previously reported domain linker predictors. These results indicate that SVMs can be used to predict domain linkers, and that loop-length-dependent characteristics are useful for improving SVM prediction performances.

  9. Novel pH-Sensitive Cationic Lipids with Linear Ortho Ester Linkers for Gene Delivery

    PubMed Central

    Chen, Haigang; Zhang, Huizhen; Thor, Der; Rahimian, Roshanak; Guo, Xin

    2012-01-01

    In an effort to develop pH-sensitive lipoplexes for efficient gene delivery, we report three novel cationic lipids containing a linear ortho ester linker that conjugates either the headgroup (Type I) or one hydrocarbon chain (Type II) with the rest of the lipid molecule. The cationic lipids carry either an iodide or a chloride counterion. Compared to our previously reported cyclic ortho ester linker, the linear ortho ester linker facilitated the construction of cationic liposomes and lipoplexes with different helper lipids. The chloride counterion not only facilitated the hydration of the lipid films during liposome construction, but also enhanced the hydrolysis of the ortho ester linker in the lipoplexes. After incubation at endosomal pH 5.5, the Type I lipoplexes aggregated and destabilized the endosome-mimicking model liposomes, but not the Type II lipoplexes. The helper lipids (DOPE or cholesterol) of the lipoplexes enhanced the pH-sensitivity of the Type I lipoplexes. In CV-1 cells (monkey kidney fibroblast), the Type I ortho ester-based lipoplexes, especially those with the chloride counterion, significantly improved the gene transfection efficiency, in some cases by more than 100 fold, compared to their pH-insensitive counterparts consisting of DOTAP. The gene transfection efficiency of the ortho ester-based lipoplexes was well correlated with their rate of aggregation and membrane destabilization in response to the endosomal pH 5.5. PMID:22480493

  10. Influence of Linker Length and Composition on Enzymatic Activity and Ribosomal Binding of Neomycin Dimers

    PubMed Central

    Watkins, Derrick; Kumar, Sunil; Green, Keith D.

    2015-01-01

    The human and bacterial A site rRNA binding as well as the aminoglycoside-modifying enzyme (AME) activity against a series of neomycin B (NEO) dimers is presented. The data indicate that by simple modifications of linker length and composition, substantial differences in rRNA selectivity and AME activity can be obtained. We tested five different AMEs with dimeric NEO dimers that were tethered via triazole, urea, and thiourea linkages. We show that triazole-linked dimers were the worst substrates for most AMEs, with those containing the longer linkers showing the largest decrease in activity. Thiourea-linked dimers that showed a decrease in activity by AMEs also showed increased bacterial A site binding, with one compound (compound 14) even showing substantially reduced human A site binding. The urea-linked dimers showed a substantial decrease in activity by AMEs when a conformationally restrictive phenyl linker was introduced. The information learned herein advances our understanding of the importance of the linker length and composition for the generation of dimeric aminoglycoside antibiotics capable of avoiding the action of AMEs and selective binding to the bacterial rRNA over binding to the human rRNA. PMID:25896697

  11. Streptomyces lividans glycosylates the linker region of a beta-1,4-glycanase from Cellulomonas fimi.

    PubMed Central

    Ong, E; Kilburn, D G; Miller, R C; Warren, R A

    1994-01-01

    The beta-1,4-glycanase Cex of the gram-positive bacterium Cellulomonas fimi is a glycoprotein comprising a C-terminal cellulose-binding domain connected to an N-terminal catalytic domain by a linker containing only prolyl and threonyl (PT) residues. Cex is also glycosylated by Streptomyces lividans. The glycosylation of Cex produced in both C. fimi and S. lividans protects the enzyme from proteolysis. When the gene fragments encoding the cellulose-binding domain of Cex (CBDCex), the PT linker plus CBDCex (PT-CBDCex), and the catalytic domain plus CBDCex of Cex were expressed in S. lividans, only PT-CBDCex was glycosylated. Therefore, all the glycans must be O linked because only the PT linker was glycosylated. A glycosylated form and a nonglycosylated form of PT-CBDCex were produced by S. lividans. The glycosylated form of PT-CBDCex was heterogeneous; its average carbohydrate content was approximately 10 mol of D-mannose equivalents per mol of protein, but the glycans contained from 4 to 12 alpha-D-mannosyl and alpha-D-galactosyl residues. Glycosylated Cex from S. lividans was also heterogeneous. The presence of glycans on PT-CBDCex increased its affinity for bacterial microcrystalline cellulose. The location of glycosylation only on the linker region of Cex correlates with the properties conferred on the enzyme by the glycans. Images PMID:8106343

  12. Novel pH-sensitive cationic lipids with linear ortho ester linkers for gene delivery.

    PubMed

    Chen, Haigang; Zhang, Huizhen; Thor, Der; Rahimian, Roshanak; Guo, Xin

    2012-06-01

    In an effort to develop pH-sensitive lipoplexes for efficient gene delivery, we report three novel cationic lipids containing a linear ortho ester linker that conjugates either the headgroup (Type I) or one hydrocarbon chain (Type II) with the rest of the lipid molecule. The cationic lipids carry either an iodide or a chloride counterion. Compared to our previously reported cyclic ortho ester linker, the linear ortho ester linker facilitated the construction of cationic liposomes and lipoplexes with different helper lipids. The chloride counterion not only facilitated the hydration of the lipid films during liposome construction, but also enhanced the hydrolysis of the ortho ester linker in the lipoplexes. After incubation at endosomal pH 5.5, the Type I lipoplexes aggregated and destabilized the endosome-mimicking model liposomes, but not the Type II lipoplexes. The helper lipids (DOPE or cholesterol) of the lipoplexes enhanced the pH-sensitivity of the Type I lipoplexes. In CV-1 cells (monkey kidney fibroblast), the Type I ortho ester-based lipoplexes, especially those with the chloride counterion, significantly improved the gene transfection efficiency, in some cases by more than 100 fold, compared to their pH-insensitive counterparts consisting of DOTAP. The gene transfection efficiency of the ortho ester-based lipoplexes was well correlated with their rate of aggregation and membrane destabilization in response to the endosomal pH 5.5.

  13. Loop-linker PCR: an advanced PCR technique for genome walking.

    PubMed

    Trinh, Quoclinh; Shi, Hui; Xu, Wentao; Hao, Junran; Luo, Yunbo; Huang, Kunlun

    2012-10-01

    In this article, we developed a novel PCR method, termed loop-linker PCR, to isolate flanking sequences in transgenic crops. The novelty of this approach is its use of a stem-loop structure to design a loop-linker adapter. The adapter is designed to form a nick site when ligated with restricted DNA. This modification not only can prevent the self-ligation of adapters but also promotes the elongation of the 3' end of the loop-linker adapter to generate a stem-loop structure in the ligation products. Moreover, the suppressive effect of the stem-loop structure decreases nonspecific amplification and increases the success rate of the approach; all extension products will suppress exponential amplification except from the ligation product that contains the specific primer binding site. Using this method, 442, 1830, 107, and 512 bp left border flanking sequences were obtained from the transgenic maizes LY038, DAS-59122-7, Event 3272, and the transgenic soybean MON89788, respectively. The experimental results demonstrated that loop-linker PCR is an efficient, reliable, and cost-effective method for identifying flanking sequences in transgenic crops and could be applied for other genome walking applications.

  14. A multifunctional anomeric linker for the chemoenzymatic synthesis of complex oligosaccharides†

    PubMed Central

    Prudden, Anthony R.; Chinoy, Zoeisha S.; Wolfert, Margreet A.; Boons, Geert-Jan

    2014-01-01

    A new anomeric linker has been developed that facilitates the purification of glycans prepared by chemoenzymatic approaches and can readily give compounds that are appropriately modified for microarray development or glycan derivatives with a free reducing end that are needed as standards for the development of analytical protocols. PMID:24854112

  15. The linker pivot in Ci-VSP: the key to unlock catalysis.

    PubMed

    Hobiger, Kirstin; Utesch, Tillmann; Mroginski, Maria Andrea; Seebohm, Guiscard; Friedrich, Thomas

    2013-01-01

    In the voltage-sensitive phosphatase Ci-VSP, conformational changes in the transmembrane voltage sensor domain (VSD) are transduced to the intracellular catalytic domain (CD) leading to its dephosphorylation activity against membrane-embedded phosphoinositides. The linker between both domains is proposed to be crucial for the VSD-CD coupling. With a combined approach of electrophysiological measurements on Xenopus oocytes and molecular dynamics simulations of a Ci-VSP model embedded in a lipid bilayer, we analyzed how conformational changes in the linker mediate the interaction between the CD and the activated VSD. In this way, we identified specific residues in the linker that interact with well-defined amino acids in one of the three loops forming the active site of the protein, named TI loop. With our results, we shed light into the early steps of the coupling process between the VSD and the CD, which are based on fine-tuned electrostatic and hydrophobic interactions between the linker, the membrane and the CD.

  16. Novel nucleosomal particles containing core histones and linker DNA but no histone H1.

    PubMed

    Cole, Hope A; Cui, Feng; Ocampo, Josefina; Burke, Tara L; Nikitina, Tatiana; Nagarajavel, V; Kotomura, Naoe; Zhurkin, Victor B; Clark, David J

    2016-01-29

    Eukaryotic chromosomal DNA is assembled into regularly spaced nucleosomes, which play a central role in gene regulation by determining accessibility of control regions. The nucleosome contains ∼147 bp of DNA wrapped ∼1.7 times around a central core histone octamer. The linker histone, H1, binds both to the nucleosome, sealing the DNA coils, and to the linker DNA between nucleosomes, directing chromatin folding. Micrococcal nuclease (MNase) digests the linker to yield the chromatosome, containing H1 and ∼160 bp, and then converts it to a core particle, containing ∼147 bp and no H1. Sequencing of nucleosomal DNA obtained after MNase digestion (MNase-seq) generates genome-wide nucleosome maps that are important for understanding gene regulation. We present an improved MNase-seq method involving simultaneous digestion with exonuclease III, which removes linker DNA. Remarkably, we discovered two novel intermediate particles containing 154 or 161 bp, corresponding to 7 bp protruding from one or both sides of the nucleosome core. These particles are detected in yeast lacking H1 and in H1-depleted mouse chromatin. They can be reconstituted in vitro using purified core histones and DNA. We propose that these 'proto-chromatosomes' are fundamental chromatin subunits, which include the H1 binding site and influence nucleosome spacing independently of H1.

  17. Linker Immolation Determines Cell Killing Activity of Disulfide-Linked Pyrrolobenzodiazepine Antibody-Drug Conjugates.

    PubMed

    Zhang, Donglu; Pillow, Thomas H; Ma, Yong; Cruz-Chuh, Josefa Dela; Kozak, Katherine R; Sadowsky, Jack D; Lewis Phillips, Gail D; Guo, Jun; Darwish, Martine; Fan, Peter; Chen, Jingtian; He, Changrong; Wang, Tao; Yao, Hui; Xu, Zijin; Chen, Jinhua; Wai, John; Pei, Zhonghua; Hop, Cornelis E C A; Khojasteh, S Cyrus; Dragovich, Peter S

    2016-11-10

    Disulfide bonds could be valuable linkers for a variety of therapeutic applications requiring tunable cleavage between two parts of a molecule (e.g., antibody-drug conjugates). The in vitro linker immolation of β-mercaptoethyl-carbamate disulfides and DNA alkylation properties of associated payloads were investigated to understand the determinant of cell killing potency of anti-CD22 linked pyrrolobenzodiazepine (PBD-dimer) conjugates. Efficient immolation and release of a PBD-dimer with strong DNA alkylation properties were observed following disulfide cleavage of methyl- and cyclobutyl-substituted disulfide linkers. However, the analogous cyclopropyl-containing linker did not immolate, and the associated thiol-containing product was a poor DNA alkylator. As predicted from these in vitro assessments, the related anti-CD22 ADCs showed different target-dependent cell killing activities in WSU-DLCL2 and BJAB cell lines. These results demonstrate how the in vitro immolation models can be used to help design efficacious ADCs.

  18. Assembly of bipolar microtubule structures by passive cross-linkers and molecular motors

    NASA Astrophysics Data System (ADS)

    Johann, D.; Goswami, D.; Kruse, K.

    2016-06-01

    During cell division, sister chromatids are segregated by the mitotic spindle, a bipolar assembly of interdigitating antiparallel polar filaments called microtubules. The spindle contains the midzone, a stable region of overlapping antiparallel microtubules, that is essential for maintaining bipolarity. Although a lot is known about the molecular players involved, the mechanism underlying midzone formation and maintenance is still poorly understood. We study the interaction of polar filaments that are cross-linked by molecular motors moving directionally and by passive cross-linkers diffusing along microtubules. Using a particle-based stochastic model, we find that the interplay of motors and passive cross-linkers can generate a stable finite overlap between a pair of antiparallel polar filaments. We develop a mean-field theory to study this mechanism in detail and investigate the influence of steric interactions between motors and passive cross-linkers on the overlap dynamics. In the presence of interspecies steric interactions, passive cross-linkers mimic the behavior of molecular motors and stable finite overlaps are generated even for non-cross-linking motors. Finally, we develop a mean-field theory for a bundle of aligned polar filaments and show that they can self-organize into a spindlelike pattern. Our work suggests possible ways as to how cells can generate spindle midzones and control their extensions.

  19. DISCOVERY OF SUBSTRUCTURE IN THE SCATTER-BROADENED IMAGE OF SGR A*

    SciTech Connect

    Gwinn, C. R.; Kovalev, Y. Y.; Soglasnov, V. A.

    2014-10-10

    We have detected substructure within the smooth scattering disk of the celebrated Galactic center radio source Sagittarius A* (Sgr A*). We observed this structure at 1.3 cm wavelength with the Very Long Baseline Array together with the Green Bank Telescope, on baselines of up to 3000 km, long enough to completely resolve the average scattering disk. Such structure is predicted theoretically as a consequence of refraction by large-scale plasma fluctuations in the interstellar medium. Along with the much-studied θ{sub d}∝λ{sup 2} scaling of angular broadening θ{sub d} with observing wavelength λ, our observations indicate that the spectrum of interstellar turbulence is shallow with an inner scale larger than 300 km. The substructure is consistent with an intrinsic size of about 1 mas at 1.3 cm wavelength, as inferred from deconvolution of the average scattering. Further observations of the substructure can set stronger constraints on the properties of scattering material and on the intrinsic size of Sgr A*. These constraints will guide our understanding of the effects of scatter broadening and the emission physics near the black hole in images with the Event Horizon Telescope at millimeter wavelengths.

  20. Constraining dark matter sub-structure with the dynamics of astrophysical systems

    SciTech Connect

    González-Morales, Alma X.; Valenzuela, Octavio; Aguilar, Luis A. E-mail: octavio@astro.unam.mx

    2013-03-01

    The accuracy of the measurements of some astrophysical dynamical systems allows to constrain the existence of incredibly small gravitational perturbations. In particular, the internal Solar System dynamics (planets, Earth-Moon) opens up the possibility, for the first time, to prove the abundance, mass and size, of dark sub-structures at the Earth vicinity. We find that adopting the standard dark matter density, its local distribution can be composed by sub-solar mass halos with no currently measurable dynamical consequences, regardless of the mini-halo fraction. On the other hand, it is possible to exclude the presence of dark streams with linear mass densities higher than λ{sub st} > 10{sup −10}M{sub ☉}/AU (about the Earth mass spread along the diameter of the SS up to the Kuiper belt). In addition, we review the dynamics of wide binaries inside the dwarf spheroidal galaxies in the Milky Way. The dynamics of such kind of binaries seem to be compatible with the presence of a huge fraction of dark sub-structure, thus their existence is not a sharp discriminant of the dark matter hypothesis as been claimed before. However, there are regimes where the constraints from different astrophysical systems may reveal the sub-structure mass function cut-off scale.

  1. Model validation of the Sandia 34-Meter Test Bed Turbine using substructure modal-testing

    SciTech Connect

    Carne, T.G.; Lauffer, J.P.; Gomez, A.J.; Ashwill, T.D.

    1989-01-01

    The Sandia 34-Meter Test Bed Turbine is a vertical-axis wind turbine, thirty-four meters in diameter, designed to provide a test-bed for research in aerodynamics, structures and control. In order to design a large wind turbine, knowledge of the modal frequencies and mode shapes is essential for predicting structural response. During the design, analytical or finite element models are utilized for estimates of these modal parameters. However, when hardware becomes available, modal testing can be used to verify or update the models. The concept of substructure modal testing was developed for the Sandia 34-Meter Test Bed in order to more fully evaluate the accuracy of the finite element model. Instead of performing only one test on the entire turbine, separate tests and analyses were performed on major substructures of the turbine, including three separate blade sections, the tower supported by the guy cables, and the entire turbine. The results were then compared to analytical predictions from the finite element models of the substructures and the entire turbine. 8 refs., 6 figs., 6 tabs.

  2. Modeling the Role of Dislocation Substructure During Class M and Exponential Creep. Revised

    NASA Technical Reports Server (NTRS)

    Raj, S. V.; Iskovitz, Ilana Seiden; Freed, A. D.

    1995-01-01

    The different substructures that form in the power-law and exponential creep regimes for single phase crystalline materials under various conditions of stress, temperature and strain are reviewed. The microstructure is correlated both qualitatively and quantitatively with power-law and exponential creep as well as with steady state and non-steady state deformation behavior. These observations suggest that creep is influenced by a complex interaction between several elements of the microstructure, such as dislocations, cells and subgrains. The stability of the creep substructure is examined in both of these creep regimes during stress and temperature change experiments. These observations are rationalized on the basis of a phenomenological model, where normal primary creep is interpreted as a series of constant structure exponential creep rate-stress relationships. The implications of this viewpoint on the magnitude of the stress exponent and steady state behavior are discussed. A theory is developed to predict the macroscopic creep behavior of a single phase material using quantitative microstructural data. In this technique the thermally activated deformation mechanisms proposed by dislocation physics are interlinked with a previously developed multiphase, three-dimensional. dislocation substructure creep model. This procedure leads to several coupled differential equations interrelating macroscopic creep plasticity with microstructural evolution.

  3. RAG-3D: A search tool for RNA 3D substructures

    SciTech Connect

    Zahran, Mai; Sevim Bayrak, Cigdem; Elmetwaly, Shereef; Schlick, Tamar

    2015-08-24

    In this study, to address many challenges in RNA structure/function prediction, the characterization of RNA's modular architectural units is required. Using the RNA-As-Graphs (RAG) database, we have previously explored the existence of secondary structure (2D) submotifs within larger RNA structures. Here we present RAG-3D—a dataset of RNA tertiary (3D) structures and substructures plus a web-based search tool—designed to exploit graph representations of RNAs for the goal of searching for similar 3D structural fragments. The objects in RAG-3D consist of 3D structures translated into 3D graphs, cataloged based on the connectivity between their secondary structure elements. Each graph is additionally described in terms of its subgraph building blocks. The RAG-3D search tool then compares a query RNA 3D structure to those in the database to obtain structurally similar structures and substructures. This comparison reveals conserved 3D RNA features and thus may suggest functional connections. Though RNA search programs based on similarity in sequence, 2D, and/or 3D structural elements are available, our graph-based search tool may be advantageous for illuminating similarities that are not obvious; using motifs rather than sequence space also reduces search times considerably. Ultimately, such substructuring could be useful for RNA 3D structure prediction, structure/function inference and inverse folding.

  4. RAG-3D: A search tool for RNA 3D substructures

    DOE PAGES

    Zahran, Mai; Sevim Bayrak, Cigdem; Elmetwaly, Shereef; ...

    2015-08-24

    In this study, to address many challenges in RNA structure/function prediction, the characterization of RNA's modular architectural units is required. Using the RNA-As-Graphs (RAG) database, we have previously explored the existence of secondary structure (2D) submotifs within larger RNA structures. Here we present RAG-3D—a dataset of RNA tertiary (3D) structures and substructures plus a web-based search tool—designed to exploit graph representations of RNAs for the goal of searching for similar 3D structural fragments. The objects in RAG-3D consist of 3D structures translated into 3D graphs, cataloged based on the connectivity between their secondary structure elements. Each graph is additionally describedmore » in terms of its subgraph building blocks. The RAG-3D search tool then compares a query RNA 3D structure to those in the database to obtain structurally similar structures and substructures. This comparison reveals conserved 3D RNA features and thus may suggest functional connections. Though RNA search programs based on similarity in sequence, 2D, and/or 3D structural elements are available, our graph-based search tool may be advantageous for illuminating similarities that are not obvious; using motifs rather than sequence space also reduces search times considerably. Ultimately, such substructuring could be useful for RNA 3D structure prediction, structure/function inference and inverse folding.« less

  5. A NEW CHANNEL FOR DETECTING DARK MATTER SUBSTRUCTURE IN GALAXIES: GRAVITATIONAL LENS TIME DELAYS

    SciTech Connect

    Keeton, Charles R.; Moustakas, Leonidas A.

    2009-07-10

    We show that dark matter substructure in galaxy-scale halos perturbs the time delays between images in strong gravitational lens systems. The variance of the effect depends on the subhalo mass function, scaling as the product of the substructure mass fraction, and a characteristic mass of subhalos (namely (m {sup 2})/(m)). Time delay perturbations therefore complement gravitational lens flux ratio anomalies and astrometric perturbations by measuring a different moment of the subhalo mass function. Unlike flux ratio anomalies, 'time delay millilensing' is unaffected by dust extinction or stellar microlensing in the lens galaxy. Furthermore, we show that time delay ratios are immune to the radial profile degeneracy that usually plagues lens modeling. We lay out a mathematical theory of time delay perturbations and find it to be tractable and attractive. We predict that in 'cusp' lenses with close triplets of images, substructure may change the arrival-time order of the images (compared with smooth models). We discuss the possibility that this effect has already been observed in RX J1131-1231.

  6. Structural damage identification based on substructure sensitivity and l1 sparse regularization

    NASA Astrophysics Data System (ADS)

    Zhou, Shumei; Bao, Yuequan; Li, Hui

    2013-04-01

    Sparsity constraints are now very popular to regularize inverse problems in the field of applied mathematics. Structural damage identification is a typical inverse problem of structural dynamics and Structural damage is a spatial sparse phenomenon, i.e., structural damage occurs, only part of elements or substructures are damaged. In this paper, a structural damage identification method based on the substructure-based sensitivity analysis and the sparse constraints regularization is proposed. Substructure sensitivity analysis, the establishment of structural damage stiffness parameter variation and change of modal parameters of linear equations between the measured degrees of freedom is limited, the equations for a morbid equation. The introduction of structural damage sparsity conditions, to minimize the l1 norm optimization solution. The numerical example of the 20 bay-truss structure with considering measurement noise, incomplete of measurements and multi-damage cases are carried out. The effects of number sensor and layout to the identification results are also investigated. The results indicated that the damage locations and extents can be effectively identified by the proposed method. Additionally, the sensor location can be random arrangement, which has great significance to the sensor placement of the actual structural health monitoring because robust structural damage identification also can be obtained even a few of sensor are failure.

  7. Modulating Therapeutic Activity and Toxicity of Pyrrolobenzodiazepine Antibody-Drug Conjugates with Self-Immolative Disulfide Linkers.

    PubMed

    Pillow, Thomas H; Schutten, Melissa; Yu, Shang-Fan; Ohri, Rachana; Sadowsky, Jack; Poon, Kirsten Achilles; Solis, Willy; Zhong, Fiona; Del Rosario, Geoffrey; Go, Mary Ann T; Lau, Jeffery; Yee, Sharon; He, Jintang; Liu, Luna; Ng, Carl; Xu, Keyang; Leipold, Douglas D; Kamath, Amrita V; Zhang, Donglu; Masterson, Luke; Gregson, Stephen J; Howard, Philip W; Fang, Fan; Chen, Jinhua; Gunzner-Toste, Janet; Kozak, Katherine K; Spencer, Susan; Polakis, Paul; Polson, Andrew G; Flygare, John A; Junutula, Jagath R

    2017-02-21

    A novel disulfide linker was designed to enable a direct connection between cytotoxic pyrrolobenzodiazepine (PBD) drugs and the cysteine on a targeting antibody for use in antibody-drug conjugates (ADCs). ADCs composed of a cysteine-engineered antibody were armed with a PBD using a self-immolative disulfide linker. Both the chemical linker and the antibody site were optimized for this new bioconjugation strategy to provide a highly stable and efficacious ADC. This novel disulfide ADC was compared to a conjugate containing the same PBD drug, but attached to the antibody via a peptide linker. Both ADCs had similar efficacy in mice bearing human tumor xenografts. Safety studies in rats revealed that the disulfide-linked ADC had a higher maximum tolerated dose (MTD) than the peptide-linked ADC. Overall, these data suggest that the novel self-immolative disulfide linker represents a valuable way to construct ADCs with equivalent efficacy and improved safety.

  8. Release of 3-methyladenine from linker and core DNA of chromatin by a purified DNA glycosylase

    SciTech Connect

    Heller, E.P.; Goldthwait, D.A.

    1983-12-01

    Oligonucleosomes were isolated from (/sub 14/C)thymidine-labeled HeLa cells by digestion of the nuclei with micrococcal nuclease and were then alkylated with (/sub 3/H)methylnitrosourea. Nucleosome core particles were also prepared by further digestion of the oligonucleosomes. The distribution of /sub 3/H-labeled methyl groups in the linker versus the core DNA was established by a determination of /sub 3/H:/sub 14/C ratios in oligonucleosome and core DNA. The ratios in the core DNA of 145 and 165 base pair DNA fragments were 5.2 and 5.4, respectively, while the ratio in the oligonucleosomal DNA was 8.2. Assuming an equal mixture (as determined) of 145 and 165 base pair fragments of DNA in the 185 base pair repeat, the relative concentration of /sub 3/H methyl groups in the linker versus the core DNA was 4.2. Thus, 45% of the /sub 3/H methyl groups were in the linker DNA, and 55% were in the core DNA. Some shielding of the DNA was evident during alkylation. The concentrations of alkyl groups on the linker and core DNA were 67 and 12% of that found on free DNA alkylated under comparable conditions. No evidence for preferential shielding of the major or minor groove was observed. The purified 3-methyladenine DNA glycosylase I of Escherichia coli released approximately 37% of the 3-methyladenine from the linker DNA and 13% from the core DNA. The limited enzymatic removal of 3-methyladenine in vitro compared to the efficient removal in vivo suggests that conformational changes of the oligonucleosome and core structure must occur for total repair.

  9. Polyglycine hydrolases secreted by Pleosporineae fungi that target the linker region of plant class IV chitinases.

    PubMed

    Naumann, Todd A; Wicklow, Donald T; Price, Neil P J

    2014-06-01

    Cmps (chitinase-modifying proteins) are fungal proteases that truncate plant class IV chitinases by cleaving near their N-termini. We previously described Fv-cmp, a fungalysin protease that cleaves a conserved glycine-cysteine bond within the hevein domain. In the present paper we describe a new type of cmp, polyglycine hydrolases, as proteases that selectively cleave glycine-glycine peptide bonds within the polyglycine linker of plant class IV chitinases. Polyglycine hydrolases were purified from Cochliobolus carbonum (syn. Bipolaris zeicola; Bz-cmp) and Epicoccum sorghi (syn. Phoma sorghina; Es-cmp) and were shown to cleave three different maize class IV chitinase substrates. The proteolytic cleavage sites were assessed by SDS/PAGE and MALDI-TOF-MS and indicated the cleavage of multiple peptide bonds within the polyglycine linker regions. Site-directed mutagenesis was used to produce mutants of maize ChitB chitinase in which two serine residues in its linker were systematically modified to glycine. Serine to glycine changes in the ChitB linker resulted in higher susceptibility to truncation by Bz-cmp and altered substrate specificity for Bz-cmp and Es-cmp, such that different glycine-glycine peptide bonds were cleaved. Removal of the hevein domain led to loss of Es-cmp activity, indicating that interactions outside of the active site are important for recognition. Our findings demonstrate that plant class IV chitinases with polyglycine linkers are targeted for truncation by selective polyglycine hydrolases that are secreted by plant pathogenic fungi. This novel proteolysis of polyglycine motifs is previously unreported, but the specificity is similar to that of bacterial lysostaphin proteases, which cleave pentaglycine cross-links from peptidoglycan.

  10. Localized buckling of a microtubule surrounded by randomly distributed cross linkers.

    PubMed

    Jin, M Z; Ru, C Q

    2013-07-01

    Microtubules supported by surrounding cross linkers in eukaryotic cells can bear a much higher compressive force than free-standing microtubules. Different from some previous studies, which treated the surroundings as a continuum elastic foundation or elastic medium, the present paper develops a micromechanics numerical model to examine the role of randomly distributed discrete cross linkers in the buckling of compressed microtubules. First, the proposed numerical approach is validated by reproducing the uniform multiwave buckling mode predicted by the existing elastic-foundation model. For more realistic buckling of microtubules surrounded by randomly distributed cross linkers, the present numerical model predicts that the buckling mode is localized at one end in agreement with some known experimental observations. In particular, the critical force for localized buckling, predicted by the present model, is insensitive to microtubule length and can be about 1 order of magnitude lower than those given by the elastic-foundation model, which suggests that the elastic-foundation model may have overestimated the critical force for buckling of microtubules in vivo. In addition, unlike the elastic-foundation model, the present model can capture the effect of end conditions on the critical force and wavelength of localized buckling. Based on the known data of spacing and elastic constants of cross linkers available in literature, the critical force and wavelength of the localized buckling mode, predicted by the present model, are compared to some experimental data with reasonable agreement. Finally, two empirical formulas are proposed for the critical force and wavelength of the localized buckling of microtubules surrounded by cross linkers.

  11. Arsenic metalation of seaweed Fucus vesiculosus metallothionein: the importance of the interdomain linker in metallothionein.

    PubMed

    Ngu, Thanh T; Lee, Janice A; Rushton, Moira K; Stillman, Martin J

    2009-09-22

    The presence of metallothionein in seaweed Fucus vesiculosus has been suggested as the protecting agent against toxic metals in the contaminated waters it can grow in. We report the first kinetic pathway data for A3+ binding to an algal metallothionein, F. vesiculosus metallothionein (rfMT). The time and temperature dependence of the relative concentrations of apo-rfMT and the five As-containing species have been determined following mixing of As3+ and apo-rfMT using electrospray ionization mass spectrometry (ESI MS). Kinetic analysis of the detailed time-resolved mass spectral data for As3+ metalation allows the simulation of the metalation reactions showing the consumption of apo-rfMT, the formation and consumption of As1- to As4-rfMT, and subsequent, final formation of As5-rfMT. The kinetic model proposed here provides a stepwise analysis of the metalation reaction showing time-resolved occupancy of the Cys7 and the Cys9 domain. The rate constants (M(-1) s(-1)) calculated from the fits for the 7-cysteine gamma domain are k1gamma, 19.8, and k2gamma, 1.4, and for the 9-cysteine beta domain are k1beta, 16.3, k2beta, 9.1, and k3beta, 2.2. The activation energies and Arrhenius factors for each of the reaction steps are also reported. rfMT has a long 14 residue linker, which as we show from analysis of the ESI MS data, allows each of its two domains to bind As3+ independently of each other. The analysis provides for the first time an explanation of the differing metal-binding properties of two-domain MTs with linkers of varying lengths, suggesting further comparison between plant (with long linkers) and mammalian (with short linkers) metallothioneins will shed light on the role of the interdomain linker.

  12. Predicting solubilisation features of ternary phase diagrams of fully dilutable lecithin linker microemulsions.

    PubMed

    Nouraei, Mehdi; Acosta, Edgar J

    2017-06-01

    Fully dilutable microemulsions (μEs), used to design self-microemulsifying delivery system (SMEDS), are formulated as concentrate solutions containing oil and surfactants, without water. As water is added to dilute these systems, various μEs are produced (water-swollen reverse micelles, bicontinuous systems, and oil-swollen micelles), without the onset of phase separation. Currently, the formulation dilutable μEs follows a trial and error approach that has had a limited success. The objective of this work is to introduce the use of the hydrophilic-lipophilic-difference (HLD) and net-average-curvature (NAC) frameworks to predict the solubilisation features of ternary phase diagrams of lecithin-linker μEs and the use of these predictions to guide the formulation of dilutable μEs. To this end, the characteristic curvatures (Cc) of soybean lecithin (surfactant), glycerol monooleate (lipophilic linker) and polyglycerol caprylate (hydrophilic linker) and the equivalent alkane carbon number (EACN) of ethyl caprate (oil) were obtained via phase scans with reference surfactant-oil systems. These parameters were then used to calculate the HLD of lecithin-linkers-ethyl caprate microemulsions. The calculated HLDs were able to predict the phase transitions observed in the phase scans. The NAC was then used to fit and predict phase volumes obtained from salinity phase scans, and to predict the solubilisation features of ternary phase diagrams of the lecithin-linker formulations. The HLD-NAC predictions were reasonably accurate, and indicated that the largest region for dilutable μEs was obtained with slightly negative HLD values. The NAC framework also predicted, and explained, the changes in microemulsion properties along dilution lines.

  13. Absolute proper motions to B approximately 22.5: Evidence for kimematical substructure in halo field stars

    NASA Technical Reports Server (NTRS)

    Majewski, Steven R.; Munn, Jeffrey A.; Hawley, Suzanne L.

    1994-01-01

    Radial velocities have been obtained for six of nine stars identified on the basis of similar distances and common, extreme transverse velocities in the proper motion survey of Majewski (1992) as a candidate halo moving group at the north Galactic pole. These radial velocities correspond to velocities perpendicular to the Galactic plane which span the range -48 +/- 21 to -128 +/- 9 km/sec (but a smaller range, -48 +/- 21 to -86 +/- 19 km/sec, when only our own measurements are considered), significantly different than the expected distribution, with mean 0 km/sec, for a random sample of either halo or thick disk stars. The probability of picking such a set of radial velocities at random is less than 1%. Thus the radial velocity data support the hypothesis that these stars constitute part of a halo moving group or star stream at a distance of approximately 4-5 kpc above the Galactic plane. If real, this moving group is evidence for halo phase space substructure which may be the fossil remains of a destroyed globular cluster, Galactic satellite, or Searle & Zinn (1978) 'fragment.'

  14. Clays, common

    USGS Publications Warehouse

    Virta, R.L.

    1998-01-01

    Part of a special section on the state of industrial minerals in 1997. The state of the common clay industry worldwide for 1997 is discussed. Sales of common clay in the U.S. increased from 26.2 Mt in 1996 to an estimated 26.5 Mt in 1997. The amount of common clay and shale used to produce structural clay products in 1997 was estimated at 13.8 Mt.

  15. Bayesian strong gravitational-lens modelling on adaptive grids: objective detection of mass substructure in Galaxies

    NASA Astrophysics Data System (ADS)

    Vegetti, S.; Koopmans, L. V. E.

    2009-01-01

    We introduce a new adaptive and fully Bayesian grid-based method to model strong gravitational lenses with extended images. The primary goal of this method is to quantify the level of luminous and dark mass substructure in massive galaxies, through their effect on highly magnified arcs and Einstein rings. The method is adaptive on the source plane, where a Delaunay tessellation is defined according to the lens mapping of a regular grid on to the source plane. The Bayesian penalty function allows us to recover the best non-linear potential-model parameters and/or a grid-based potential correction and to objectively quantify the level of regularization for both the source and potential. In addition, we implement a Nested-Sampling technique to quantify the errors on all non-linear mass model parameters - marginalized over all source and regularization parameters - and allow an objective ranking of different potential models in terms of the marginalized evidence. In particular, we are interested in comparing very smooth lens mass models with ones that contain mass substructures. The algorithm has been tested on a range of simulated data sets, created from a model of a realistic lens system. One of the lens systems is characterized by a smooth potential with a power-law density profile, 12 include a Navarro, Frenk and White (NFW) dark matter substructure of different masses and at different positions and one contains two NFW dark substructures with the same mass but with different positions. Reconstruction of the source and lens potential for all of these systems shows the method is able, in a realistic scenario, to identify perturbations with masses >~107Msolar when located on the Einstein ring. For positions both inside and outside of the ring, masses of at least 109Msolar are required (i.e. roughly the Einstein ring of the perturber needs to overlap with that of the main lens). Our method provides a fully novel and objective test of mass substructure in massive

  16. Student Commons

    ERIC Educational Resources Information Center

    Gordon, Douglas

    2010-01-01

    Student commons are no longer simply congregation spaces for students with time on their hands. They are integral to providing a welcoming environment and effective learning space for students. Many student commons have been transformed into spaces for socialization, an environment for alternative teaching methods, a forum for large group meetings…

  17. Measurement of Residual Flexibility for Substructures Having Prominent Flexible Interfaces

    NASA Technical Reports Server (NTRS)

    Tinker, Michael L.; Bookout, Paul S.

    1994-01-01

    Verification of a dynamic model of a constrained structure requires a modal survey test of the physical structure and subsequent modification of the model to obtain the best agreement possible with test data. Constrained-boundary or fixed-base testing has historically been the most common approach for verifying constrained mathematical models, since the boundary conditions of the test article are designed to match the actual constraints in service. However, there are difficulties involved with fixed-base testing, in some cases making the approach impractical. It is not possible to conduct a truly fixed-base test due to coupling between the test article and the fixture. In addition, it is often difficult to accurately simulate the actual boundary constraints, and the cost of designing and constructing the fixture may be prohibitive. For use when fixed-base testing proves impractical or undesirable, alternate free-boundary test methods have been investigated, including the residual flexibility technique. The residual flexibility approach has been treated analytically in considerable detail and has had limited frequency response measurements for the method. This concern is well-justified for a number of reasons. First, residual flexibilities are very small numbers, typically on the order of 1.0E-6 in/lb for translational diagonal terms, and orders of magnitude smaller for off-diagonal values. This poses difficulty in obtaining accurate and noise-free measurements, especially for points removed from the excitation source. A second difficulty encountered in residual measurements lies in obtaining a clean residual function in the process of subtracting synthesized modal data from a measured response function. Inaccuracies occur since modes are not subtracted exactly, but only to the accuracy of the curve fits for each mode; these errors are compounded with increasing distance from the excitation point. In this paper, the residual flexibility method is applied to a simple

  18. Development of Bioorthogonally Degradable Linkers and Polymers Using alpha-Azidoethers

    NASA Astrophysics Data System (ADS)

    Rajagopalan, Chandrasekhar Ramasubramanian

    Degradable polymers have gained a lot of attention in recent years for applications in biotechnology and medicine. External control over polymer degradation can be obtained by incorporating functional groups that cleave in the presence of triggers that would normally be absent in biological environments, i.e. are bioorthogonal. This thesis explores the use of chemically cleavable alpha-azidoethers as a new method to obtain external control over the degradation behavior of polymers. My first goal is to illustrate the potential of alpha-azidoethers toward developing cleavable linkers. We have studied the relationship between alpha-azidoether structure and hydrolytic stability, to prepare linkers that withstand background hydrolytic cleavage until they are exposed to the cleaving trigger. The cleavage kinetics of the alpha-azidoether functional group was quantified. In addition to the conventionally used tris(2-carboxyethyl)phosphine (TCEP), dihydrolipoic acid (DHLA), a previously unexplored, biocompatible reducing agent, was also evaluated as a cleaving trigger. Based on these results, we have proposed design rules for utilizing alpha-azidoethers as cleavable linkers in applications that require bioorthogonal control over linker cleavage. Secondly, the alpha-azidoether cleavable linker chemistry was implemented into the development of polymeric materials. Two different types of polymers were developed. Polyamides incorporating alpha-azidoethers along the backbone were synthesized, and their physical properties and chemically triggered degradation behavior were characterized. The degradation timescale of these polymers can be tuned simply by manipulating the concentration of the externally applied chemical trigger. The alpha-azidoether functional group was then utilized to develop a unique triggered-release polymeric adhesive for potential applications in dental adhesive formulations. A methacrylamide-phosphonate adhesive monomer incorporating an alpha

  19. The synaptotagmin 1 linker may function as an electrostatic zipper that opens for docking but closes for fusion pore opening.

    PubMed

    Lai, Ying; Lou, Xiaochu; Jho, Yongseok; Yoon, Tae-Young; Shin, Yeon-Kyun

    2013-11-15

    Syt1 (synaptotagmin 1), a major Ca2+ sensor for fast neurotransmitter release, contains tandem Ca2+-binding C2 domains (C2AB), a single transmembrane α-helix and a highly charged 60-residue-long linker in between. Using single-vesicle-docking and content-mixing assays we found that the linker region of Syt1 is essential for its two signature functions: Ca2+-independent vesicle docking and Ca2+-dependent fusion pore opening. The linker contains the basic-amino-acid-rich N-terminal region and the acidic-amino-acid-rich C-terminal region. When the charge segregation was disrupted, fusion pore opening was slowed, whereas docking was unchanged. Intramolecular disulfide cross-linking between N- and C-terminal regions of the linker or deletion of 40 residues from the linker reduced docking while enhancing pore opening, although the changes were subtle. EPR analysis showed Ca2+-induced line broadening reflecting a conformational change in the linker region. Thus the results of the present study suggest that the electrostatically bipartite linker region may extend for docking and fold to facilitate pore opening.

  20. QCI Common

    SciTech Connect

    McCaskey, Alexander J.

    2016-11-18

    There are many common software patterns and utilities for the ORNL Quantum Computing Institute that can and should be shared across projects. Otherwise we find duplication of code which adds unwanted complexity. This is a software product seeks to alleviate this by providing common utilities such as object factories, graph data structures, parameter input mechanisms, etc., for other software products within the ORNL Quantum Computing Institute. This work enables pure basic research, has no export controlled utilities, and has no real commercial value.

  1. cis-Apa: a practical linker for the microwave-assisted preparation of cyclic pseudopeptides via RCM cyclative cleavage.

    PubMed

    Baron, Alice; Verdié, Pascal; Martinez, Jean; Lamaty, Frédéric

    2011-02-04

    A new linker cis-5-aminopent-3-enoic acid (cis-Apa) was prepared for the synthesis of cyclic pseudopeptides by cyclization-cleavage by using ring-closing methatesis (RCM). We developed a new synthetic pathway for the preparation of the cis-Apa linker that was tested in the cyclization-cleavage process of different RGD peptide sequences. Different macrocyclic peptidomimetics were prepared by using this integrated microwave-assisted method, showing that the readily available cis-Apa amino acid is well adapted as a linker in the cyclization-cleavage process.

  2. Effects of branched O-glycosylation on a semiflexible peptide linker.

    PubMed

    Johnson, Quentin R; Lindsay, Richard J; Raval, Sherin R; Dobbs, Jeremy S; Nellas, Ricky B; Shen, Tongye

    2014-02-27

    Glycosylation is an essential modification of proteins and lipids by the addition of carbohydrate residues. These attached carbohydrates range from single monomers to elaborate branched glycans. Here, we examine how the level of glycosylation affects the conformation of a semiflexible peptide linker using the example of the hinge peptide from immunoglobulin A. Three sets of atomistic models of this hinge peptide with varying degrees of glycosylation are constructed to probe how glycosylation affects the physical properties of the linker. We found that glycosylation greatly altered the predominant conformations of the peptide, causing it to become elongated in reference to the unglycosylated form. Furthermore, glycosylation restricts the conformational exploration of the peptide. At the residue level, glycans are found to introduce a bias for the formation of more extended secondary structural elements for glycosylated serines. Additionally, the flexibility of this semiflexible proline-rich peptide is significantly reduced by glycosylation.

  3. DNA-duplex linker for AFM-SELEX of DNA aptamer against human serum albumin.

    PubMed

    Takenaka, Musashi; Okumura, Yuzo; Amino, Tomokazu; Miyachi, Yusuke; Ogino, Chiaki; Kondo, Akihiko

    2017-02-15

    DNA-duplex interactions in thymines and adenins are used as a linker for the novel methodology of Atomic Force Microscope-Systematic Evolution of Ligands by EXpotential enrichment (AFM-SELEX). This study used the hydrogen bonds in 10 mer of both thymines (T10) and adenines (A10). Initially, the interactive force in T10-A10 was measured by AFM, which returned an average interactive force of approximately 350pN. Based on this result, DNA aptamers against human serum albumin could be selected in the 4th round, and 15 different clones could be sequenced. The lowest dissociation constant of the selected aptamer was identified via surface plasmon resonance, and it proved to be identical to that of the commercial aptamer. Therefore, specific hydrogen bonds in DNA can be useful linkers for AFM-SELEX.

  4. Opening ZIF-8: a catalytically active zeolitic imidazolate framework of sodalite topology with unsubstituted linkers.

    PubMed

    Karagiaridi, Olga; Lalonde, Marianne B; Bury, Wojciech; Sarjeant, Amy A; Farha, Omar K; Hupp, Joseph T

    2012-11-14

    A zeolitic imidazolate framework material of SOD topology possessing primarily unsubstituted imidazolate (im) linkers has been synthesized via solvent-assisted linker exchange (SALE) of ZIF-8. The structure of the new material, SALEM-2, has been confirmed through (1)H NMR and powder and single-crystal X-ray diffraction. SALEM-2 is the first example of a porous Zn(im)(2) ZIF possessing a truly zeolitic topology that can be obtained in bulk quantities. Upon treatment with n-butyllithium, the open analogue exhibits Brønsted base catalysis that cannot be accomplished by the parent material ZIF-8. Additionally, it displays a different size cutoff for uptake and release of molecular guests than does ZIF-8.

  5. ATP-Driven Remodeling of the Linker Domain in the Dynein Motor

    PubMed Central

    Roberts, Anthony J.; Malkova, Bara; Walker, Matt L.; Sakakibara, Hitoshi; Numata, Naoki; Kon, Takahide; Ohkura, Reiko; Edwards, Thomas A.; Knight, Peter J.; Sutoh, Kazuo; Oiwa, Kazuhiro; Burgess, Stan A.

    2012-01-01

    Summary Dynein ATPases are the largest known cytoskeletal motors and perform critical functions in cells: carrying cargo along microtubules in the cytoplasm and powering flagellar beating. Dyneins are members of the AAA+ superfamily of ring-shaped enzymes, but how they harness this architecture to produce movement is poorly understood. Here, we have used cryo-EM to determine 3D maps of native flagellar dynein-c and a cytoplasmic dynein motor domain in different nucleotide states. The structures show key sites of conformational change within the AAA+ ring and a large rearrangement of the “linker” domain, involving a hinge near its middle. Analysis of a mutant in which the linker “undocks” from the ring indicates that linker remodeling requires energy that is supplied by interactions with the AAA+ modules. Fitting the dynein-c structures into flagellar tomograms suggests how this mechanism could drive sliding between microtubules, and also has implications for cytoplasmic cargo transport. PMID:22863569

  6. The H1 linker histones: multifunctional proteins beyond the nucleosomal core particle

    PubMed Central

    Hergeth, Sonja P; Schneider, Robert

    2015-01-01

    The linker histone H1 family members are a key component of chromatin and bind to the nucleosomal core particle around the DNA entry and exit sites. H1 can stabilize both nucleosome structure and higher-order chromatin architecture. In general, H1 molecules consist of a central globular domain with more flexible tail regions at both their N- and C-terminal ends. The existence of multiple H1 subtypes and a large variety of posttranslational modifications brings about a considerable degree of complexity and makes studying this protein family challenging. Here, we review recent progress in understanding the function of linker histones and their subtypes beyond their role as merely structural chromatin components. We summarize current findings on the role of H1 in heterochromatin formation, transcriptional regulation and embryogenesis with a focus on H1 subtypes and their specific modifications. PMID:26474902

  7. Destabilization of the Outer and Inner Mitochondrial Membranes by Core and Linker Histones

    PubMed Central

    Cascone, Annunziata; Bruelle, Celine; Lindholm, Dan; Bernardi, Paolo; Eriksson, Ove

    2012-01-01

    Background Extensive DNA damage leads to apoptosis. Histones play a central role in DNA damage sensing and may mediate signals of genotoxic damage to cytosolic effectors including mitochondria. Methodology/Principal Findings We have investigated the effects of histones on mitochondrial function and membrane integrity. We demonstrate that both linker histone H1 and core histones H2A, H2B, H3, and H4 bind strongly to isolated mitochondria. All histones caused a rapid and massive release of the pro-apoptotic intermembrane space proteins cytochrome c and Smac/Diablo, indicating that they permeabilize the outer mitochondrial membrane. In addition, linker histone H1, but not core histones, permeabilized the inner membrane with a collapse of the membrane potential, release of pyridine nucleotides, and mitochondrial fragmentation. Conclusions We conclude that histones destabilize the mitochondrial membranes, a mechanism that may convey genotoxic signals to mitochondria and promote apoptosis following DNA damage. PMID:22523586

  8. Connecting two proteins using a fusion alpha helix stabilized by a chemical cross linker

    PubMed Central

    Jeong, Woo Hyeon; Lee, Haerim; Song, Dong Hyun; Eom, Jae-Hoon; Kim, Sun Chang; Lee, Hee-Seung; Lee, Hayyoung; Lee, Jie-Oh

    2016-01-01

    Building a sophisticated protein nano-assembly requires a method for linking protein components in a predictable and stable structure. Most of the cross linkers available have flexible spacers. Because of this, the linked hybrids have significant structural flexibility and the relative structure between their two components is largely unpredictable. Here we describe a method of connecting two proteins via a ‘fusion α helix' formed by joining two pre-existing helices into a single extended helix. Because simple ligation of two helices does not guarantee the formation of a continuous helix, we used EY-CBS, a synthetic cross linker that has been shown to react selectively with cysteines in α-helices, to stabilize the connecting helix. Formation and stabilization of the fusion helix was confirmed by determining the crystal structures of the fusion proteins with and without bound EY-CBS. Our method should be widely applicable for linking protein building blocks to generate predictable structures. PMID:26980593

  9. Intercalation and buckling instability of DNA linker within locked chromatin fiber

    NASA Astrophysics Data System (ADS)

    Victor, Jean-Marc; Ben-Haïm, Eli; Lesne, A.

    2002-12-01

    The chromatin fiber is a complex of DNA and specific proteins called histones forming the first structural level of organization of eukaryotic chromosomes. In tightly organized chromatin fibers, the short segments of naked DNA linking the nucleosomes are strongly end constrained. Longitudinal thermal fluctuations in these linkers allow intercalative mode of protein binding. We show that mechanical constraints generated in the first stage of the binding process induce linker DNA buckling; buckling in turn modifies the binding energies and activation barriers and creates a force of decondensation at the chromatin fiber level. The unique structure and properties of DNA thus yield a novel physical mechanism of buckling instability that might play a key role in the regulation of gene expression.

  10. Linking two DNA duplexes with a rigid linker for DNA nanotechnology

    PubMed Central

    Tashiro, Ryu; Iwamoto, Masahiro; Morinaga, Hironobu; Emura, Tomoko; Hidaka, Kumi; Endo, Masayuki; Sugiyama, Hiroshi

    2015-01-01

    DNA has recently emerged as a promising material for the construction of nanosized architectures. Chemically modified DNA has been suggested to be an important component of such architectural building blocks. We have designed and synthesized a novel H-shaped DNA oligonucleotide dimer that is cross-linked with a structurally rigid linker composed of phenylene and ethynylene groups. A rotatable DNA unit was constructed through the self-assembly of this H-shaped DNA component and two complementary DNA oligonucleotides. In addition to the rotatable unit, a locked DNA unit containing two H-shaped DNA components was also constructed. As an example of an extended locked structure, a hexagonal DNA origami dimer and oligomer were constructed by using H-shaped DNA as linkers. PMID:26130712

  11. Connecting two proteins using a fusion alpha helix stabilized by a chemical cross linker

    NASA Astrophysics Data System (ADS)

    Jeong, Woo Hyeon; Lee, Haerim; Song, Dong Hyun; Eom, Jae-Hoon; Kim, Sun Chang; Lee, Hee-Seung; Lee, Hayyoung; Lee, Jie-Oh

    2016-03-01

    Building a sophisticated protein nano-assembly requires a method for linking protein components in a predictable and stable structure. Most of the cross linkers available have flexible spacers. Because of this, the linked hybrids have significant structural flexibility and the relative structure between their two components is largely unpredictable. Here we describe a method of connecting two proteins via a `fusion α helix' formed by joining two pre-existing helices into a single extended helix. Because simple ligation of two helices does not guarantee the formation of a continuous helix, we used EY-CBS, a synthetic cross linker that has been shown to react selectively with cysteines in α-helices, to stabilize the connecting helix. Formation and stabilization of the fusion helix was confirmed by determining the crystal structures of the fusion proteins with and without bound EY-CBS. Our method should be widely applicable for linking protein building blocks to generate predictable structures.

  12. Atomic Structure of Clathrin: A β Propeller Terminal Domain Joins an α Zigzag Linker

    PubMed Central

    ter Haar, Ernst; Musacchio, Andrea; Harrison, Stephen C.; Kirchhausen, Tomas

    2015-01-01

    Summary Clathrin triskelions form the lattice that organizes recruitment of proteins to coated pits and helps drive vesiculation of the lipid bilayer. We report the crystal structure at 2.6 Å resolution of a 55 kDa N-terminal fragment from the 190 kDa clathrin heavy chain. The structure comprises the globular “terminal domain” and the linker that joins it to the end of a triskelion leg. The terminal domain is a seven-blade β propeller, a structure well adapted to interaction with multiple partners, such as the AP-1 and AP-2 sorting adaptor complexes and the nonvisual arrestins. The linker is an α-helical zigzag emanating from the propeller domain. We propose that this simple motif may extend into the rest of the clathrin leg. PMID:9827808

  13. The H1 linker histones: multifunctional proteins beyond the nucleosomal core particle.

    PubMed

    Hergeth, Sonja P; Schneider, Robert

    2015-11-01

    The linker histone H1 family members are a key component of chromatin and bind to the nucleosomal core particle around the DNA entry and exit sites. H1 can stabilize both nucleosome structure and higher-order chromatin architecture. In general, H1 molecules consist of a central globular domain with more flexible tail regions at both their N- and C-terminal ends. The existence of multiple H1 subtypes and a large variety of posttranslational modifications brings about a considerable degree of complexity and makes studying this protein family challenging. Here, we review recent progress in understanding the function of linker histones and their subtypes beyond their role as merely structural chromatin components. We summarize current findings on the role of H1 in heterochromatin formation, transcriptional regulation and embryogenesis with a focus on H1 subtypes and their specific modifications.

  14. The extraordinary amount of substructure in the Hubble Frontier Fields cluster Abell 2744

    NASA Astrophysics Data System (ADS)

    Jauzac, M.; Eckert, D.; Schwinn, J.; Harvey, D.; Baugh, C. M.; Robertson, A.; Bose, S.; Massey, R.; Owers, M.; Ebeling, H.; Shan, H. Y.; Jullo, E.; Kneib, J.-P.; Richard, J.; Atek, H.; Clément, B.; Egami, E.; Israel, H.; Knowles, K.; Limousin, M.; Natarajan, P.; Rexroth, M.; Taylor, P.; Tchernin, C.

    2016-12-01

    We present a joint optical/X-ray analysis of the massive galaxy cluster Abell 2744 (z = 0.308). Our strong- and weak-lensing analysis within the central region of the cluster, i.e. at R < 1 Mpc from the brightest cluster galaxy, reveals eight substructures, including the main core. All of these dark matter haloes are detected with a significance of at least 5σ and feature masses ranging from 0.5 to 1.4 × 1014 M⊙ within R < 150 kpc. Merten et al. and Medezinski et al. substructures are also detected by us. We measure a slightly higher mass for the main core component than reported previously and attribute the discrepancy to the inclusion of our tightly constrained strong-lensing mass model built on Hubble Frontier Fields data. X-ray data obtained by XMM-Newton reveal four remnant cores, one of them a new detection, and three shocks. Unlike Merten et al., we find all cores to have both dark and luminous counterparts. A comparison with clusters of similar mass in the Millennium XXL simulations yields no objects with as many massive substructures as observed in Abell 2744, confirming that Abell 2744 is an extreme system. We stress that these properties still do not constitute a challenge to Λ cold dark matter, as caveats apply to both the simulation and the observations: for instance, the projected mass measurements from gravitational lensing and the limited resolution of the subhaloes finders. We discuss implications of Abell 2744 for the plausibility of different dark matter candidates and, finally, measure a new upper limit on the self-interaction cross-section of dark matter of σDM < 1.28 cm2 g-1 (68 per cent CL), in good agreement with previous results from Harvey et al.

  15. Spectroscopy of Bright Quest RR Lyrae Stars: Velocity Substructures Toward Virgo

    NASA Astrophysics Data System (ADS)

    Vivas, A. Katherina; Jaffé, Yara L.; Zinn, Robert; Winnick, Rebeccah; Duffau, Sonia; Mateu, Cecilia

    2008-10-01

    Using a sample of 43 bright (V < 16.1, distance <13 kpc) RR Lyrae stars (RRLS) from the QUasar Equatorial Survey with spectroscopic radial velocities and metallicities, we find that several separate halo substructures contribute to the Virgo overdensity (VOD). While there is little evidence of a halo substructure in the spatial distribution of these stars, their distribution in radial velocity reveals two moving groups. These results are reinforced when the sample is combined with a sample of blue horizontal branch stars that were identified in the Sloan Digital Sky Survey, and the combined sample provides evidence for one additional moving group. These groups correspond to peaks in the radial velocity distribution of a sample of F-type main-sequence stars that was recently observed in the same direction by the Sloan Extension for Galactic Understanding and Exploration (SEGUE), although in one case the RRLS and F star groups may not lie at the same distance. One of the new substructures has a very narrow range in metallicity, which is more consistent with it being the debris from a destroyed globular cluster than from a dwarf galaxy. A small concentration of stars have radial velocities that are similar to the Virgo Stellar Stream that was identified previously in a fainter sample of RRLS. Our results suggest that this feature extends to distances as short as ~12 kpc, compared to its previous detection at ~19 kpc. None of the new groups and only one star in the sample have velocities that are consistent with membership in the leading tidal stream from the Sagittarius dwarf spheroidal galaxy, which some authors have suggested is the origin of the VOD.

  16. Unprecedented folding in linker based flexible tripodal molecule and their conformational analysis

    NASA Astrophysics Data System (ADS)

    Gaurav, Archana; Kumar, Ranjeet; Gupta, Hariom; Ravikumar, K.; Sridhar, B.; Tewari, Ashish Kumar

    2017-04-01

    Here, we first time report the flexible tripodal molecules, contained propylene as a linker, thiocyanuric acid as central core and, p-nitro phenol 1 and pyridazinone 2 as terminal for conformational studies. The conformational studies of these tripodal molecules have been carried by X-ray crystallography, 2D-NOESY spectra and computational studies. Both the molecules have shown folded conformations in solid and solution state however solid state conformation is not stable in gaseous state.

  17. Application of a substructuring technique to the problem of crack extension and closure

    NASA Technical Reports Server (NTRS)

    Armen, H., Jr.

    1974-01-01

    A substructuring technique, originally developed for the efficient reanalysis of structures, is incorporated into the methodology associated with the plastic analysis of structures. An existing finite-element computer program that accounts for elastic-plastic material behavior under cyclic loading was modified to account for changing kinematic constraint conditions - crack growth and intermittent contact of crack surfaces in two dimensional regions. Application of the analysis is presented for a problem of a centercrack panel to demonstrate the efficiency and accuracy of the technique.

  18. SPECTROSCOPIC OBSERVATIONS OF AN EVOLVING FLARE RIBBON SUBSTRUCTURE SUGGESTING ORIGIN IN CURRENT SHEET WAVES

    SciTech Connect

    Brannon, S. R.; Longcope, D. W.; Qiu, J.

    2015-09-01

    We present imaging and spectroscopic observations from the Interface Region Imaging Spectrograph of the evolution of the flare ribbon in the SOL2014-04-18T13:03 M-class flare event, at high spatial resolution and time cadence. These observations reveal small-scale substructure within the ribbon, which manifests as coherent quasi-periodic oscillations in both position and Doppler velocities. We consider various alternative explanations for these oscillations, including modulation of chromospheric evaporation flows. Among these, we find the best support for some form of wave localized to the coronal current sheet, such as a tearing mode or Kelvin–Helmholtz instability.

  19. Bidirectional Connected Control Method Applied to an Experimental Structural Model Split into Four Substructures

    NASA Astrophysics Data System (ADS)

    Watanabe, T.; Seto, K.; Toyoda, H.; Takano, T.

    2016-09-01

    Connected Control Method (CCM) is a well-known mechanism in the field of civil structural vibration control that utilizes mutual reaction forces between plural buildings connected by dampers as damping force. However, the fact that CCM requires at least two buildings to obtain reaction force prevents CCM from further development. In this paper, a novel idea to apply CCM onto a single building by splitting the building into four substructures is presented. An experimental model structure split into four is built and CCM is applied by using four magnetic dampers. Experimental analysis is carried out and basic performance and effectiveness of the presented idea is confirmed.

  20. Exclusive processes: Tests of coherent QCD phenomena and nucleon substructure at CEBAF

    SciTech Connect

    Brodsky, S.J.

    1994-07-01

    Measurements of exclusive processes such as electroproduction, photoproduction, and Compton scattering are among the most sensitive probes of proton structure and coherent phenomena in quantum chromodynamics. The continuous electron beam at CEBAF, upgraded in laboratory energy to 10--12 GeV, will allow a systematic study of exclusive, semi-inclusive, and inclusive reactions in a kinematic range well-tuned to the study of fundamental nucleon and nuclear substructure. I also discuss the potential at CEBAF for studying novel QCD phenomena at the charm production threshold, including the possible production of nuclear-bound quarkonium.

  1. An early neutrino experiment: how we missed quark substructure in 1963

    NASA Astrophysics Data System (ADS)

    Perkins, D. H.

    2013-12-01

    Some 50 years after the event seems to be an appropriate time at which to take a long look back at one of the early neutrino experiments at CERN. This report is principally about a failure in a 1963 bubble chamber experiment to detect substructure in the nucleon, a year before the quark concept was invented by Gell-Mann and Zweig, and some five years before the existence of quarks as real dynamical objects was definitely established in deep inelastic electron scattering experiments at Stanford.

  2. Triazole bridges as versatile linkers in electron donor-acceptor conjugates

    PubMed Central

    de Miguel, Gustavo; Wielopolski, Mateusz; Schuster, David I.; Fazio, Michael A; Lee, Olivia P.; Haley, Christopher K.; Ortiz, Angy L.; Echegoyen, Luis; Clark, Timothy; Guldi, Dirk M.

    2011-01-01

    Aromatic triazoles have been frequently used as π-conjugated linkers in intramolecular electron transfer processes. To gain a deeper understanding of the electron mediating function of triazoles, we have synthesized a family of new triazole-based electron donor-acceptor conjugates. We have connected porphyrins and fullerenes through a central triazole moiety – (ZnP-Tri-C60) – each with a single change in their connection through the linker. An extensive photophysical and computational investigation reveals that the electron transfer dynamics – charge separation and charge recombination – in the different ZnP-Tri-C60 conjugates reflect a significant influence of the connectivity at the triazole linker. Except for m4m-ZnP-Tri-C60 17, the conjugates exhibit through-bond electron transfer with varying rate constants. Since the through-bond distance is nearly equal in the ZnP-Tri-C60 conjugates, the variation in charge separation and charge recombination dynamics is mainly associated with the electronic properties of the conjugates, including orbital energies, electron affinity, and the energies of the excited states. The changes of the electronic couplings are, in turn, a consequence of the different connectivity patterns at the triazole moieties. PMID:21702513

  3. Linker engineering for fusion protein construction: Improvement and characterization of a GLP-1 fusion protein.

    PubMed

    Kong, Yuelin; Tong, Yue; Gao, Mingming; Chen, Chen; Gao, Xiangdong; Yao, Wenbing

    2016-01-01

    Protein engineering has been successfully applied in protein drug discovery. Using this technology, we previously have constructed a fusion protein by linking the globular domain of adiponectin to the C-terminus of a glucagon-like peptide-1 (GLP-1) analog. Herein, to further improve its bioactivity, we reconstructed this fusion protein by introducing linker peptides of different length and flexibility. The reconstructed fusion proteins were overexpressed in Escherichia coli and purified using nickel affinity chromatography. Their agonist activity towards receptors of GLP-1 and adiponectin were assessed in vitro by using luciferase assay and AMP-activated protein kinase (AMPK) immunoblotting, respectively. The effects of the selected fusion protein on glucose and lipid metabolism were evaluated in mice. The fusion protein reconstructed using a linker peptide of AMGPSSGAPGGGGS showed high potency in activating GLP-1 receptor and triggering AMPK phosphorylation via activating the adiponectin receptor. Remarkably, the optimized fusion protein was highly effective in lowering blood glucose and lipids in mice. Collectively, these findings demonstrate that the bioactivity of this GLP-1 fusion protein can be significantly promoted by linker engineering, and indicate that the optimized GLP-1 fusion protein is a promising lead structure for anti-diabetic drug discovery.

  4. Bifunctional bridging linker-assisted synthesis and characterization of TiO2/Au nanocomposites

    NASA Astrophysics Data System (ADS)

    Žunič, Vojka; Kurtjak, Mario; Suvorov, Danilo

    2016-11-01

    Using a simple organic bifunctional bridging linker, titanium dioxide (TiO2) nanoparticles were coupled with the Au nanoparticles to form TiO2/Au nanocomposites with a variety of Au loadings. This organic bifunctional linker, meso-2,3-dimercaptosuccinic acid, contains two types of functional groups: (i) the carboxyl group, which enables binding to the TiO2, and (ii) the thiol group, which enables binding to the Au. In addition, the organic bifunctional linker acts as a stabilizing agent to prevent the agglomeration and growth of the Au particles, resulting in the formation of highly dispersed Au nanoparticles. To form the TiO2/Au nanocomposites in a simple way, we deliberately applied a synthetic method that simultaneously ensures: (i) the capping of the Au nanoparticles and (ii) the binding of different amounts of Au to the TiO2. The TiO2/Au nanocomposites formed with this method show enhanced UV and Vis photocatalytic activities when compared to the pure TiO2 nanopowders.

  5. The human histone chaperone sNASP interacts with linker and core histones through distinct mechanisms.

    PubMed

    Wang, Huanyu; Ge, Zhongqi; Walsh, Scott T R; Parthun, Mark R

    2012-01-01

    Somatic nuclear autoantigenic sperm protein (sNASP) is a human homolog of the N1/N2 family of histone chaperones. sNASP contains the domain structure characteristic of this family, which includes a large acidic patch flanked by several tetratricopeptide repeat (TPR) motifs. sNASP possesses a unique binding specificity in that it forms specific complexes with both histone H1 and histones H3/H4. Based on the binding affinities of sNASP variants to histones H1, H3.3, H4 and H3.3/H4 complexes, sNASP uses distinct structural domains to interact with linker and core histones. For example, one of the acidic patches of sNASP was essential for linker histone binding but not for core histone interactions. The fourth TPR of sNASP played a critical role in interactions with histone H3/H4 complexes, but did not influence histone H1 binding. Finally, analysis of cellular proteins demonstrated that sNASP existed in distinct complexes that contained either linker or core histones.

  6. Unexpected role of linker position on ammonium gemini surfactant lyotropic gyroid phase stability.

    PubMed

    Sorenson, Gregory P; Mahanthappa, Mahesh K

    2016-02-28

    Arising from the water-driven self-assembly of amphiphiles over generally narrow temperature and composition phase windows, aqueous lyotropic liquid crystal (LLC) network phases are useful in applications as therapeutic delivery vehicles and templates for mesoporous material syntheses. While a clear set of amphiphile design rules that enables access to these intricate three-dimensional structures has yet to emerge, recent work indicates that bis(ammonium), bis(phosphonium), and dicarboxylate gemini ("twin tail") surfactants enable enhanced access to LLC network phases such as the double gyroid (G). In order to better understand the scope of this amphiphile design strategy, we investigated the synthesis and aqueous LLC self-assembly behaviors of a homologous series of quaternary gemini bis(ammonium) dichloride surfactants, in which we varied the position of the hydrophobic linker that connects the constituent single tail surfactants. These experiments demonstrate that the position of the linker directly impacts the maximum counterion-headgroup hydration capacity and the extent of counterion-headgroup association, all of which contribute to the aqueous lyotropic double gyroid network phase stability. Thus, judicious selection of the linker position in ionic gemini surfactants provides a new molecular design tool for manipulating LLC network phase stability.

  7. Assessment of Local Friction in Protein Folding Dynamics Using a Helix Cross-Linker

    PubMed Central

    Markiewicz, Beatrice N.; Jo, Hyunil; Culik, Robert M.; DeGrado, William F.; Gai, Feng

    2013-01-01

    Internal friction arising from local steric hindrance and/or the excluded volume effect plays an important role in controlling not only the dynamics of protein folding but also conformational transitions occurring within the native state potential well. However, experimental assessment of such local friction is difficult because it does not manifest itself as an independent experimental observable. Herein, we demonstrate, using the miniprotein trp-cage as a testbed, that it is possible to selectively increase the local mass density in a protein and hence the magnitude of local friction, thus making its effect directly measureable via folding kinetic studies. Specifically, we show that when a helix cross-linker, m-xylene, is placed near the most congested region of the trp-cage it leads to a significant decrease in both the folding rate (by a factor of 3.8) and unfolding rate (by a factor of 2.5 at 35 °C), but has little effect on protein stability. Thus, these results, in conjunction with those obtained with another cross-linked trp-cage and two uncross-linked variants, demonstrate the feasibility of using a non-perturbing cross-linker to help quantify the effect of internal friction. In addition, we estimate that an m-xylene cross-linker could lead to an increase in the roughness of the folding energy landscape by as much as 0.4-1.0kBT. PMID:24205975

  8. An activated triple bond linker enables 'click' attachment of peptides to oligonucleotides on solid support.

    PubMed

    Wenska, Malgorzata; Alvira, Margarita; Steunenberg, Peter; Stenberg, Asa; Murtola, Merita; Strömberg, Roger

    2011-11-01

    A general procedure, based on a new activated alkyne linker, for the preparation of peptide-oligonucleotide conjugates (POCs) on solid support has been developed. With this linker, conjugation is effective at room temperature (RT) in millimolar concentration and submicromolar amounts. This is made possible since the use of a readily attachable activated triple bond linker enhances the Cu(I) catalyzed 1,3-dipolar cycloaddition ('click' reaction). The preferred scheme for conjugate preparation involves sequential conjugation to oligonucleotides on solid support of (i) an H-phosphonate-based aminolinker; (ii) the triple bond donor p-(N-propynoylamino)toluic acid (PATA); and (iii) azido-functionalized peptides. The method gives conversion of oligonucleotide to the POC on solid support, and only involves a single purification step after complete assembly. The synthesis is flexible and can be carried out without the need for specific automated synthesizers since it has been designed to utilize commercially available oligonucleotide and peptide derivatives on solid support or in solution. Methodology for the ready conversion of peptides into 'clickable' azidopeptides with the possibility of selecting either N-terminus or C-terminus connection also adds to the flexibility and usability of the method. Examples of synthesis of POCs include conjugates of oligonucleotides with peptides known to be membrane penetrating and nuclear localization signals.

  9. Linker proteins enable ultrafast excitation energy transfer in the phycobilisome antenna system of Thermosynechococcus vulcanus.

    PubMed

    Nganou, C; David, L; Adir, N; Mkandawire, M

    2016-01-01

    We applied a femtosecond flash method, using induced transient absorption changes, to obtain a time-resolved view of excitation energy transfer in intact phycobilisomes of Thermosynechococcus vulcanus at room temperature. Our measurement of an excitation energy transfer rate of 888 fs in phycobilisomes shows the existence of ultrafast kinetics along the phycocyanin rod subcomplex to the allophycocyanin core that is faster than expected for previous excitation energy transfer based on Förster theory in phycobilisomes. Allophycocyanin in the core further transfers energy to the terminal emitter(s) in 17 ps. In the phycobilisome, rod doublets composed of hexameric phycocyanin discs and internal linker proteins are arranged in a parallel fashion, facilitating direct rod-rod interactions. Excitonic splitting likely drives rod absorption at 635 nm as a result of strong coupling between β84 chromophores (20 ± 1 Å) in adjacent hexamers. In comparison to the absorbance of the phycobilisome antenna system of the cyanobacterium Acaryochloris marina, which possesses a single rod structure, the linkers in T. vulcanus rods induce a 17 nm red shift in the absorbance spectrum. Furthermore, the kinetics of 888 fs indicates that the presence of the linker protein induces ultrafast excitation energy transfer between phycocyanin and allophycocyanin inside the phycobilisome, which is faster than all previous excitation energy transfer in phycobilisome subunits or sub-complexes reported to date.

  10. Two distinct promoter elements in the human rRNA gene identified by linker scanning mutagenesis.

    PubMed Central

    Haltiner, M M; Smale, S T; Tjian, R

    1986-01-01

    A cell-free RNA polymerase I transcription system was used to evaluate the transcription efficiency of 21 linker scanning mutations that span the human rRNA gene promoter. Our analysis revealed the presence of two major control elements, designated the core and upstream elements, that affect the level of transcription initiation. The core element extends from -45 to +18 relative to the RNA start site, and transcription is severely affected (up to 100-fold) by linker scanning mutations in this region. Linker scanning and deletion mutations in the upstream element, located between nucleotides -156 and -107, cause a three- to fivefold reduction in transcription. Under certain reaction conditions, such as the presence of a high ratio of protein to template or supplementation of the reaction with partially purified protein fractions, sequences upstream of the core element can have an even greater effect (20- to 50-fold) on RNA polymerase I transcription. Primer extension analysis showed that RNA synthesized from all of these mutant templates is initiated at the correct in vivo start site. To examine the functional relationship between the core and the upstream region, mutant promoters were constructed that alter the orientation, distance, or multiplicity of these control elements relative to each other. The upstream control element appears to function in only one orientation, and its position relative to the core is constrained within a fairly narrow region. Moreover, multiple core elements in close proximity to each other have an inhibitory effect on transcription. Images PMID:3785147

  11. Fivefold increase of hydrogen uptake in MOF74 through linker decorations

    NASA Astrophysics Data System (ADS)

    Arter, C. A.; Zuluaga, S.; Harrison, D.; Welchman, E.; Thonhauser, T.

    2016-10-01

    We present ab initio results for linker decorations in Mg-MOF74, i.e., attaching various metals M =Li, Na, K, Sc, Cr, Mn, Fe, Ni, Cu, Zn, Rb, Pd, Ag, and Pt near the ring of the linker, creating new strong adsorption sites and thus maximizing small-molecule uptake. We find that in most cases these decorations influence the overall form and structure of Mg-MOF74 only marginally. After the initial screening, we chose metals that bind favorably to the linker and further investigated adsorption of H2,CO2, and H2O for M =Li , Na, K, and Sc. For the case of H2 we show that up to 24 additional guest molecules can be adsorbed in the metal-organic framework (MOF) unit cell, with binding energies comparable to the original open-metal sites at the six corners of the channel. This leads to a fivefold increase of the molecule uptake in Mg-MOF74, with tremendous impact on many applications in general and hydrogen storage in particular, where the gravimetric hydrogen density increases from 1.63 to 7.28 mass % and the volumetric density increases from 15.10 to 75.50 g H2L-1 .

  12. Triazole bridges as versatile linkers in electron donor-acceptor conjugates.

    PubMed

    de Miguel, Gustavo; Wielopolski, Mateusz; Schuster, David I; Fazio, Michael A; Lee, Olivia P; Haley, Christopher K; Ortiz, Angy L; Echegoyen, Luis; Clark, Timothy; Guldi, Dirk M

    2011-08-24

    Aromatic triazoles have been frequently used as π-conjugated linkers in intramolecular electron transfer processes. To gain a deeper understanding of the electron-mediating function of triazoles, we have synthesized a family of new triazole-based electron donor-acceptor conjugates. We have connected zinc(II)porphyrins and fullerenes through a central triazole moiety--(ZnP-Tri-C(60))--each with a single change in their connection through the linker. An extensive photophysical and computational investigation reveals that the electron transfer dynamics--charge separation and charge recombination--in the different ZnP-Tri-C(60) conjugates reflect a significant influence of the connectivity at the triazole linker. Except for the m4m-ZnP-Tri-C(60)17, the conjugates exhibit through-bond photoinduced electron transfer with varying rate constants. Since the through-bond distance is nearly the same for all the synthesized ZnP-Tri-C(60) conjugates, the variation in charge separation and charge recombination dynamics is mainly associated with the electronic properties of the conjugates, including orbital energies, electron affinity, and the energies of the excited states. The changes of the electronic couplings are, in turn, a consequence of the different connectivity patterns at the triazole moieties.

  13. Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins

    PubMed Central

    Cervenka, Igor; Valnohova, Jana; Bernatik, Ondrej; Harnos, Jakub; Radsetoulal, Matej; Sedova, Katerina; Hanakova, Katerina; Potesil, David; Sedlackova, Miroslava; Salasova, Alena; Steinhart, Zachary; Angers, Stephane; Schulte, Gunnar; Hampl, Ales; Zdrahal, Zbynek; Bryja, Vitezslav

    2016-01-01

    Dishevelled (DVL) is a key scaffolding protein and a branching point in Wnt signaling pathways. Here, we present conclusive evidence that DVL regulates the centrosomal cycle. We demonstrate that DVL dishevelled and axin (DIX) domain, but not DIX domain-mediated multimerization, is essential for DVL’s centrosomal localization. DVL accumulates during the cell cycle and associates with NIMA-related kinase 2 (NEK2), which is able to phosphorylate DVL at a multitude of residues, as detected by a set of novel phospho-specific antibodies. This creates interfaces for efficient binding to CDK5 regulatory subunit-associated protein 2 (CDK5RAP2) and centrosomal Nek2-associated protein 1 (C-NAP1), two proteins of the centrosomal linker. Displacement of DVL from the centrosome and its release into the cytoplasm on NEK2 phosphorylation is coupled to the removal of linker proteins, an event necessary for centrosomal separation and proper formation of the mitotic spindle. Lack of DVL prevents NEK2-controlled dissolution of loose centrosomal linker and subsequent centrosomal separation. Increased DVL levels, in contrast, sequester centrosomal NEK2 and mimic monopolar spindle defects induced by a dominant negative version of this kinase. Our study thus uncovers molecular crosstalk between centrosome and Wnt signaling. PMID:27486244

  14. Solid-Phase Synthesis of Triostin A Using a Symmetrical Bis(diphenylmethyl) Linker System.

    PubMed

    Sable, Ganesh A; Lim, Dongyeol

    2015-08-07

    Triostin A is a symmetric bicyclic depsipeptide with very potent antitumoral activity because of its bisintercalation into DNA. In this study, we report a new synthetic strategy that exploits a structural symmetry of triostin A. First, we prepared a novel symmetric linker molecule that is labile under mildly acidic conditions and suitable for a solid-phase synthesis procedure. Two Cys units were attached to a linker-resin conjugate via their free thiol groups, and double deprotection and double coupling reactions were then applied to synthesize linear tetradepsipeptides. Subsequently, the key biscyclization of the tetradepsipeptides was performed on the resin, and the resulting cyclic octapeptide was detached from the linker-resin conjugate to give a peptide with two free thiols. Finally, triostin A was obtained by oxidizing the free thiols in solution to produce a disulfide. The yield was improved through exploration of two different solid-phase synthetic approaches under similar strategy. Mainly, this strategy was developed to enable the ease and rapid preparation of libraries of symmetric bicyclic depsipeptides. It also addresses several synthetic problems with our synthesis, including diketopiperazine (DKP) formation, poor cyclization yields and preparation of noncommercial N-methyl amino acids in good yields.

  15. Substructures with luminosity modulation and horizontal oscillation in pulsating patch: Principal component analysis application to pulsating aurora

    NASA Astrophysics Data System (ADS)

    Nishiyama, Takanori; Miyoshi, Yoshizumi; Katoh, Yuto; Sakanoi, Takeshi; Kataoka, Ryuho; Okano, Shoichi

    2016-03-01

    We observed a mesoscale aurora (100 km × 100 km) with patchy structure and equatorward propagation at Poker Flat Research Range on 1 December 2011. Fast Fourier transform (FFT) analysis revealed that this pulsating patch clearly exhibited temporal variations that can be categorized into two types: on-off pulsation (7.8-10 s) with large amplitudes and luminosity modulations excited during on phase with a frequency of about 3.0 Hz. In addition, we applied principal component analysis (PCA) to time series image data of the pulsating aurora for the first time. Time coefficients were estimated by PCA for the whole patch and the substructures were consistent with those obtained from the FFT analysis, and therefore, we concluded that PCA is capable of decomposing several structures that have different coherent spatiotemporal characteristics. Another new insight in this study is that the rapid variations were highly localized; they were excited in only the substructures embedded in the whole structure. Moreover, the whole patch propagated equatorward because of E × B drift of cold plasma, while the substructures did not show such systematic propagation but rather forward-backward oscillations. The horizontal scale of the substructures was estimated to be no smaller than 410 km at the magnetic equator, which is comparable to that of the wave packet structure of a whistler mode chorus perpendicular to the field line. We suggest that the apparent horizontal oscillation of the substructures is associated with field-aligned propagations of the whistler mode chorus in a duct.

  16. How to remain nonfolded and pliable: the linkers in modular α-amylases as a case study.

    PubMed

    Feller, Georges; Dehareng, Dominique; Lage, Jean-Luc Da

    2011-07-01

    The primary structure of linkers in a new class of modular α-amylases constitutes a paradigm of the structural basis that allows a polypeptide to remain nonfolded, extended and pliable. Unfolding is mediated through a depletion of hydrophobic residues and an enrichment of hydrophilic residues, amongst which Ser and Thr are over-represented. An extended and flexible conformation is promoted by the sequential arrangement of Pro and Gly, which are the most abundant residues in these linkers. This is complemented by charge repulsion, charge clustering and disulfide-bridged loops. Molecular dynamics simulations suggest the existence of conformational transitions resulting from a transient and localized hydrophobic collapse, arising from the peculiar composition of the linkers. Accordingly, these linkers should not be regarded as fully disordered, but rather as possessing various discrete structural patterns allowing them to fulfill their biological function as a free energy reservoir for concerted motions between structured domains.

  17. Extremely stretchable thermosensitive hydrogels by introducing slide-ring polyrotaxane cross-linkers and ionic groups into the polymer network.

    PubMed

    Bin Imran, Abu; Esaki, Kenta; Gotoh, Hiroaki; Seki, Takahiro; Ito, Kohzo; Sakai, Yasuhiro; Takeoka, Yukikazu

    2014-10-08

    Stimuli-sensitive hydrogels changing their volumes and shapes in response to various stimulations have potential applications in multiple fields. However, these hydrogels have not yet been commercialized due to some problems that need to be overcome. One of the most significant problems is that conventional stimuli-sensitive hydrogels are usually brittle. Here we prepare extremely stretchable thermosensitive hydrogels with good toughness by using polyrotaxane derivatives composed of α-cyclodextrin and polyethylene glycol as cross-linkers and introducing ionic groups into the polymer network. The ionic groups help the polyrotaxane cross-linkers to become well extended in the polymer network. The resulting hydrogels are surprisingly stretchable and tough because the cross-linked α-cyclodextrin molecules can move along the polyethylene glycol chains. In addition, the polyrotaxane cross-linkers can be used with a variety of vinyl monomers; the mechanical properties of the wide variety of polymer gels can be improved by using these cross-linkers.

  18. Impact of linker engineering on the catalytic activity of metal–organic frameworks containing Pd(II)–bipyridine complexes

    SciTech Connect

    Li, Xinle; Van Zeeland, Ryan; Maligal-Ganesh, Raghu V.; Pei, Yuchen; Power, Gregory; Stanley, Levi; Huang, Wenyu

    2016-08-09

    A series of mixed-linker bipyridyl metal–organic framework (MOF)-supported palladium(II) catalysts were used to elucidate the electronic and steric effects of linker substitution on the activity of these catalysts in the context of Suzuki–Miyaura cross-coupling reactions. m-6,6'-Me2bpy-MOF-PdCl2 exhibited 110- and 496-fold enhancements in activity compared to nonfunctionalized m-bpy-MOF-PdCl2 and m-4,4'-Me2bpy-MOF-PdCl2, respectively. Furthermore, this result clearly demonstrates that the stereoelectronic properties of metal-binding linker units are critical to the activity of single-site organometallic catalysts in MOFs and highlights the importance of linker engineering in the design and development of efficient MOF catalysts.

  19. Impact of linker engineering on the catalytic activity of metal–organic frameworks containing Pd(II)–bipyridine complexes

    DOE PAGES

    Li, Xinle; Van Zeeland, Ryan; Maligal-Ganesh, Raghu V.; ...

    2016-08-09

    A series of mixed-linker bipyridyl metal–organic framework (MOF)-supported palladium(II) catalysts were used to elucidate the electronic and steric effects of linker substitution on the activity of these catalysts in the context of Suzuki–Miyaura cross-coupling reactions. m-6,6'-Me2bpy-MOF-PdCl2 exhibited 110- and 496-fold enhancements in activity compared to nonfunctionalized m-bpy-MOF-PdCl2 and m-4,4'-Me2bpy-MOF-PdCl2, respectively. Furthermore, this result clearly demonstrates that the stereoelectronic properties of metal-binding linker units are critical to the activity of single-site organometallic catalysts in MOFs and highlights the importance of linker engineering in the design and development of efficient MOF catalysts.

  20. Structure-Function Studies of Escherichia coli RpoH (σ32) by In Vitro Linker Insertion Mutagenesis

    PubMed Central

    Narberhaus, Franz; Balsiger, Sylvia

    2003-01-01

    The sigma factor RpoH (σ32) is the key regulator of the heat shock response in Escherichia coli. Many structural and functional properties of the sigma factor are poorly understood. To gain further insight into RpoH regions that are either important or dispensable for its cellular activity, we generated a collection of tetrapeptide insertion variants by a recently established in vitro linker insertion mutagenesis technique. Thirty-one distinct insertions were obtained, and their sigma factor activity was analyzed by using a groE-lacZ reporter fusion in an rpoH-negative background. Our study provides a map of permissive sites which tolerate linker insertions and of functionally important regions at which a linker insertion impairs sigma factor activity. Selected linker insertion mutants will be discussed in the light of known sigma factor properties and in relation to a modeled structure of an RpoH fragment containing region 2. PMID:12700252

  1. Structure-function studies of Escherichia coli RpoH (sigma32) by in vitro linker insertion mutagenesis.

    PubMed

    Narberhaus, Franz; Balsiger, Sylvia

    2003-05-01

    The sigma factor RpoH (sigma(32)) is the key regulator of the heat shock response in Escherichia coli. Many structural and functional properties of the sigma factor are poorly understood. To gain further insight into RpoH regions that are either important or dispensable for its cellular activity, we generated a collection of tetrapeptide insertion variants by a recently established in vitro linker insertion mutagenesis technique. Thirty-one distinct insertions were obtained, and their sigma factor activity was analyzed by using a groE-lacZ reporter fusion in an rpoH-negative background. Our study provides a map of permissive sites which tolerate linker insertions and of functionally important regions at which a linker insertion impairs sigma factor activity. Selected linker insertion mutants will be discussed in the light of known sigma factor properties and in relation to a modeled structure of an RpoH fragment containing region 2.

  2. Endothelial dysfunction exacerbates renal interstitial fibrosis through enhancing fibroblast Smad3 linker phosphorylation in the mouse obstructed kidney.

    PubMed

    Sun, Yu Bo Yang; Qu, Xinli; Li, Xueling; Nikolic-Paterson, David J; Li, Jinhua

    2013-01-01

    Endothelial dysfunction and enhanced transforming growth factor-β (TGF-β)/Smad3 signalling are common features of progressive renal fibrosis. This study investigated a potential link between these mechanisms. In unilateral ureteric obstruction (UUO) we observed an acute (6 hr) down-regulation of nitric oxide synthase 3 (NOS3/eNOS) levels and increased phosphorylation of the linker region of Smad3 at T179 and S208 in Smad3/JNK complexes. These events preceded Smad3 C-terminal domain phosphorylation and the induction of myofibroblast proliferation at 48 hrs. Mice deficient in NOS3 showed enhanced myofibroblast proliferation and collagen accumulation compared to wild type mice in a 7 day UUO model. This was associated with enhanced phosphorylation of Smad3 T179 and S208 by 92% and 88%, respectively, whereas Smad3-C-terminal phosphorylation was not affected. Resolvin D1 (RvD1) can suppress renal fibrosis in the UUO model, and further analysis herein showed that RvD1 protected against endothelial dysfunction and suppressed Smad3/JNK complex formation with a consequent reduction in phosphorylation of Smad3 T179 and S208 by 78% and 65%, respectively, while Smad3 C-terminal phosphorylation was unaltered. In vitro, conditioned media from mouse microvascular endothelial cells (MMEC) treated with a general inhibitor of nitric oxide synthase (L-NAME) augmented the proliferation and collagen production of renal fibroblasts (NRK49F cells) compared to control MMEC media and this was associated with increased phosphorylation of JNK and Smad3 T179 and S208, whereas Smad3-C-terminal domain phosphorylation was unaffected. The addition of RvD1 to L-NAME treated MMEC abrogated these effects of the conditioned media on renal fibroblasts. Finally, Smad3 T179/V and S208/A mutations significantly inhibit TGF-β1 induced up-regulation collagen I promoter. In conclusion, these data suggest that endothelial dysfunction can exacerbate renal interstitial fibrosis through increased fibroblast

  3. [Hydrolysis of chimeric proteins by enteropeptidase at the specific linker (Asp)4Lys depending on refolding conditions].

    PubMed

    Shibanova, E D; Mikhaĭlova, A G; Aleksandrov, S L; Rumsh, L D

    2000-07-01

    Refolding from inclusion bodies of chimeric proteins containing the enteropeptidase-specific linker (Asp)4Lys was carried out. It was shown that, depending on the refolding conditions, chimeric proteins function as substrates or inhibitors of the enteropeptidase. The efficiency of the enteropeptidase hydrolysis of chimeric proteins containing the (Asp)4Lys linker may depend not only on the amino acid sequence of the protein binding site for the enzyme but also on the site conformation.

  4. The unstructured linker arms of Mlh1-Pms1 are important for interactions with DNA during mismatch repair.

    PubMed

    Plys, Aaron J; Rogacheva, Maria V; Greene, Eric C; Alani, Eric

    2012-09-14

    DNA mismatch repair (MMR) models have proposed that MSH (MutS homolog) proteins identify DNA polymerase errors while interacting with the DNA replication fork. MLH (MutL homolog) proteins (primarily Mlh1-Pms1 in baker's yeast) then survey the genome for lesion-bound MSH proteins. The resulting MSH-MLH complex formed at a DNA lesion initiates downstream steps in repair. MLH proteins act as dimers and contain long (20-30 nm) unstructured arms that connect two terminal globular domains. These arms can vary between 100 and 300 amino acids in length, are highly divergent between organisms, and are resistant to amino acid substitutions. To test the roles of the linker arms in MMR, we engineered a protease cleavage site into the Mlh1 linker arm domain of baker's yeast Mlh1-Pms1. Cleavage of the Mlh1 linker arm in vitro resulted in a defect in Mlh1-Pms1 DNA binding activity, and in vivo proteolytic cleavage resulted in a complete defect in MMR. We then generated a series of truncation mutants bearing Mlh1 and Pms1 linker arms of varying lengths. This work revealed that MMR is greatly compromised when portions of the Mlh1 linker are removed, whereas repair is less sensitive to truncation of the Pms1 linker arm. Purified complexes containing truncations in Mlh1 and Pms1 linker arms were analyzed and found to have differential defects in DNA binding that also correlated with the ability to form a ternary complex with Msh2-Msh6 and mismatch DNA. These observations are consistent with the unstructured linker domains of MLH proteins providing distinct interactions with DNA during MMR.

  5. ATPase domain and interdomain linker play a key role in aggregation of mitochondrial Hsp70 chaperone Ssc1.

    PubMed

    Blamowska, Marta; Sichting, Martin; Mapa, Koyeli; Mokranjac, Dejana; Neupert, Walter; Hell, Kai

    2010-02-12

    The co-chaperone Hep1 is required to prevent the aggregation of mitochondrial Hsp70 proteins. We have analyzed the interaction of Hep1 with mitochondrial Hsp70 (Ssc1) and the determinants in Ssc1 that make it prone to aggregation. The ATPase and peptide binding domain (PBD) of Hsp70 proteins are connected by a linker segment that mediates interdomain communication between the domains. We show here that the minimal Hep1 binding entity of Ssc1 consists of the ATPase domain and the interdomain linker. In the absence of Hep1, the ATPase domain with the interdomain linker had the tendency to aggregate, in contrast to the ATPase domain with the mutated linker segment or without linker, and in contrast to the PBD. The closest homolog of Ssc1, bacterial DnaK, and a Ssc1 chimera, in which a segment of the ATPase domain of Ssc1 was replaced by the corresponding segment from DnaK, did not aggregate in Delta hep1 mitochondria. The propensity to aggregate appears to be a specific property of the mitochondrial Hsp70 proteins. The ATPase domain in combination with the interdomain linker is crucial for aggregation of Ssc1. In conclusion, our results suggest that interdomain communication makes Ssc1 prone to aggregation. Hep1 counteracts aggregation by binding to this aggregation-prone conformer.

  6. Afro-derived Amazonian populations: inferring continental ancestry and population substructure.

    PubMed

    Lopes Maciel, Luana Gomes; Ribeiro Rodrigues, Elzemar Martins; Carneiro Dos Santos, Ney Pereira; Ribeiro Dos Santos, Ândrea; Guerreiro, João Farias; Santos, Sidney

    2011-10-01

    A panel of Ancestry Informative Markers (AIMs) was used to identify population substructure and estimate individual and overall interethnic admixture in 294 individuals from seven African-derived communities of the Brazilian Amazon. A panel of 48 biallelic markers, representing the insertion (IN) or the deletion (DEL) of small DNA fragments, was employed for this purpose. Overall interethnic admixture estimates showed high miscegenation with other ethnic groups in all populations (between 46% and 64%). The proportion of ancestral genes varied significantly among individuals of the sample: the contribution of African genes varied between 12% and 75%; of European genes between 10% and 73%; and of Amerindians genes between 8% and 66%. The obtained data reveal a high contribution of Amerindian genes in these communities, unlike in other African-derived communities of the Northeast and the South of Brazil. In addition, the majority of the Amerindian contribution may result from the preferential inclusion of indigenous women in the African descent groups. High heterogeneity of the proportion of interethnic admixture among analyzed individuals was found when the proportion of ancestral genes of each individual of the sample was estimated. This heterogeneity is reflected in the fact that four populations can be considered as substructured and that the global African descent sample is possibly formed by two subpopulations.

  7. Substructural organization, dislocation plasticity and harmonic generation in cyclically stressed wavy slip metals

    NASA Astrophysics Data System (ADS)

    Cantrell, John H.

    2004-03-01

    Organized substructural arrangements of dislocations formed in wavy slip, face-centred-cubic metals during cyclic stress-induced fatigue are shown analytically to engender a substantial nonlinearity in the microelastic-plastic deformation resulting from an impressed stress perturbation. The non-Hookean stress-strain relationship is quantified by a material nonlinearity parameter b that for a given fatigue state is highly sensitive to the volume fractions of veins and persistent slip bands (PSBs), PSB internal stresses, dislocation multipole configurations, dislocation loop lengths, dipole heights and the densities of secondary dislocations in the substructures. The effects on b of vacancy, microcrack and macrocrack formation are also addressed. The connection between b and acoustic harmonic generation is obtained. The model is applied to calculations of b for fatigued polycrystalline nickel as a function of per cent life to fracture. For cyclic stress-controlled loading at 241 MPa, the model predicts a monotonic increase in b of ca. 360% over the fatigue life. For strain-controlled loading at a total strain of 1.75 × 10-3, a monotonic increase in b of ca. 375% over the fatigue life is predicted.

  8. Detailed analysis of Japanese population substructure with a focus on the southwest islands of Japan.

    PubMed

    Nishiyama, Takeshi; Kishino, Hirohisa; Suzuki, Sadao; Ando, Ryosuke; Niimura, Hideshi; Uemura, Hirokazu; Horita, Mikako; Ohnaka, Keizo; Kuriyama, Nagato; Mikami, Haruo; Takashima, Naoyuki; Mastuo, Keitaro; Guang, Yin; Wakai, Kenji; Hamajima, Nobuyuki; Tanaka, Hideo

    2012-01-01

    Uncovering population structure is important for properly conducting association studies and for examining the demographic history of a population. Here, we examined the Japanese population substructure using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC), which covers all but the northern region of Japan. Using 222 autosomal loci from 4502 subjects, we investigated population substructure by estimating F(ST) among populations, testing population differentiation, and performing principal component analysis (PCA) and correspondence analysis (CA). All analyses revealed a low but significant differentiation between the Amami Islanders and the mainland Japanese population. Furthermore, we examined the genetic differentiation between the mainland population, Amami Islanders and Okinawa Islanders using six loci included in both the Pan-Asian SNP (PASNP) consortium data and the J-MICC data. This analysis revealed that the Amami and Okinawa Islanders were differentiated from the mainland population. In conclusion, we revealed a low but significant level of genetic differentiation between the mainland population and populations in or to the south of the Amami Islands, although genetic variation between both populations might be clinal. Therefore, the possibility of population stratification must be considered when enrolling the islander population of this area, such as in the J-MICC study.

  9. Structural health monitoring system of Ironton-Russell bridge during substructure construction

    NASA Astrophysics Data System (ADS)

    Dalvi, Aditi; Norouzi, Mehdi; Hunt, Victor; Helmicki, Arthur

    2016-04-01

    Monitoring a complex structure has gained popularity worldwide to ensure safety and longevity of the structure. Structural Health Monitoring (SHM) systems have been employed for highway bridges to increase the effectiveness of their in-service inspection, to help measure its degradation or damage, and hence, to ensure it's safe and reliable operation. SHM may also be employed during the construction of a structure in order to ensure the safety and performance of the construction process. Monitoring during construction can also help designers compare the actual behavior of a structure with design models especially because of increasing development of accelerated or otherwise novel construction techniques. Analyzing the behavior of a structure at different stages of construction may also help later define some of the abnormal responses during the lifespan of a bridge. This paper overviews the SHM system of the Ironton-Russell Bridge, Ohio at the construction stage of its substructure. The stages involved in monitoring such as instrumentation of sensors, acquiring data from the sensors, data processing that includes a warning system, static analysis of the data collected and website are detailed in this paper. In addition to this, the effect of construction events as observed by the sensor data for the substructure is analyzed in detail thus validating the capability of the monitoring system.

  10. In silico Prediction of Drug Induced Liver Toxicity Using Substructure Pattern Recognition Method.

    PubMed

    Zhang, Chen; Cheng, Feixiong; Li, Weihua; Liu, Guixia; Lee, Philip W; Tang, Yun

    2016-04-01

    Drug-induced liver injury (DILI) is a leading cause of acute liver failure in the US and less severe liver injury worldwide. It is also one of the major reasons of drug withdrawal from the market. Thus, DILI has become one of the most important concerns of drugs, and should be predicted in very early stage of drug discovery process. In this study, a comprehensive data set containing 1317 diverse compounds was collected from publications. Then, high accuracy classification models were built using five machine learning methods based on MACCS and FP4 fingerprints after evaluating by substructure pattern recognition method. The best model was built using SVM method together with FP4 fingerprint at the IG value threshold of 0.0005. Its overall predictive accuracies were 79.7 % and 64.5 % for the training and test sets, separately, which yielded overall accuracy of 75.0 % for the external validation dataset, consisting of 88 compounds collected from a benchmark DILI database - the Liver Toxicity Knowledge Base. This model could be used for drug-induced liver toxicity prediction. Moreover, some key substructure patterns correlated with drug-induced liver toxicity were also identified as structural alerts.

  11. The build-up of the Coma cluster by infalling substructures

    NASA Astrophysics Data System (ADS)

    Adami, C.; Biviano, A.; Durret, F.; Mazure, A.

    2005-11-01

    We present a new multiwavelength analysis of the Coma cluster subclustering based on recent X-ray data and on a compilation of nearly 900 redshifts. We characterize subclustering using the Serna & Gerbal (1996, A&A, 309, 65) hierarchical method, which makes use of galaxy positions, redshifts, and magnitudes, and identify 17 groups. One of these groups corresponds to the main cluster, one is the well known group associated with the infalling galaxy NGC 4839, and one is associated with NGC 4911/NGC 4926. About one third of the 17 groups have velocity distributions centered on the velocities of the very bright cluster galaxies they contain (magnitudes R < 13). In order to search for additional substructures, we made use of the isophotes of X-ray brightness residuals left after the subtraction of the best-fit β-model from the overall X-ray gas distribution (Neumann et al. 2003, A&A, 400, 811). We selected galaxies within each of these isophotes and compared their velocity distributions with that of the whole cluster. We confirm in this way the two groups associated, respectively, with NGC 4839, and with the southern part of the extended western substructure visible in X-rays. We discuss the group properties in the context of a scenario in which Coma is built by the accretion of groups infalling from the surrounding large-scale structure. We estimate the recent mass accretion rate of Coma and compare it with hierarchical models of cluster evolution.

  12. Mexican mestizo population sub-structure: effects on genetic and forensic statistical parameters.

    PubMed

    Noris, Gino; Santana, Carla; Meraz-Ríos, Marco Antonio; de Lourdes Munoz, María; Majluf-Cruz, Abraham; Magaña, Jonathan J; Granados, Julio; Quezada, Rosa; Revilla, María Cristina; Martínez-Salas, Sergio; Xihuitl, Salvador; Martínez de la Escalera, Gonzalo; Díaz-Badillo, Alvaro; Calderon-Aranda, Emma S; Gómez, Rocío

    2012-12-01

    Since Mexican mestizos are an admixed population, it is necessary to determine the effects that the substructure of the population has on genetic and forensic parameters. With this aim, a study was performed with 15 STR loci (CODIS plus D2S1338 and D19S433) on 1,640 unrelated Mexican mestizos. We determine allele and genotypic frequencies observing departure from Hardy-Weinberg expectation (12 out of 15 loci, with an excess of homozygotes, Fis > 0), as well as pairs of loci in an apparent linkage disequilibrium (13 of 92 loci). We conducted a test for genetic population stratification, the results show that the Mexican mestizo population is substructured into three subgroups, which are in HW and linkage equilibrium. The combination of the 15 loci in the whole population has high forensic efficiency with the capacity to genetically discriminate one individual in one quintillion (1/10(18)). Our data potentially validates the use of these 15 STR loci to establish forensic identity and parentage testing for legal purposes, and offers a powerful tool for genetic variation analysis. However, given that the population is stratified, we highly recommend applying a correction with the inbreeding coefficient in calculations of paternity and forensic studies to avoid erroneous assumptions.

  13. Mining significant substructure pairs for interpreting polypharmacology in drug-target network.

    PubMed

    Takigawa, Ichigaku; Tsuda, Koji; Mamitsuka, Hiroshi

    2011-02-23

    A current key feature in drug-target network is that drugs often bind to multiple targets, known as polypharmacology or drug promiscuity. Recent literature has indicated that relatively small fragments in both drugs and targets are crucial in forming polypharmacology. We hypothesize that principles behind polypharmacology are embedded in paired fragments in molecular graphs and amino acid sequences of drug-target interactions. We developed a fast, scalable algorithm for mining significantly co-occurring subgraph-subsequence pairs from drug-target interactions. A noteworthy feature of our approach is to capture significant paired patterns of subgraph-subsequence, while patterns of either drugs or targets only have been considered in the literature so far. Significant substructure pairs allow the grouping of drug-target interactions into clusters, covering approximately 75% of interactions containing approved drugs. These clusters were highly exclusive to each other, being statistically significant and logically implying that each cluster corresponds to a distinguished type of polypharmacology. These exclusive clusters cannot be easily obtained by using either drug or target information only but are naturally found by highlighting significant substructure pairs in drug-target interactions. These results confirm the effectiveness of our method for interpreting polypharmacology in drug-target network.

  14. Applying Genetic Programming with Substructure Discovery to a Traffic Signal Control Problem

    NASA Astrophysics Data System (ADS)

    Kumagai, Juncichi; Ojima, Yasuo; Takashige, Souichi; Kameya, Yoshitaka; Sato, Taisuke

    Nowadays the increase of traffic causes numerous serious traffic jams, and traffic signals are desired to work adaptively for dynamic traffic flows. In this paper, we view such a problem of traffic signal control as a multi-agent problem where each signal has a controlling agent, and aim to make the agents work cooperatively depending on the traffic status. To build such an agent program automatically, we introduce genetic programming (GP), an evolutionary method for program construction. In GP, it is known as important to encapsulate the substructures of a program which leads to higher fitness to the environment, and we propose a new encapsulation method using an efficient technique for discovering frequent substructures, which has been recently proposed in the data mining field. We also conducted a simulation with a real traffic data, and confirmed that GP with our encapsulation method outperforms the normal GP. It is also observed that the best individual has a communication part that chooses an appropriate communication area and adapts to the traffic status.

  15. The Substructure of the Solar Corona Observed in the Hi-C Telescope

    NASA Technical Reports Server (NTRS)

    Winebarger, A.; Cirtain, J.; Golub, L.; DeLuca, E.; Savage, S.; Alexander, C.; Schuler, T.

    2014-01-01

    In the summer of 2012, the High-resolution Coronal Imager (Hi-C) flew aboard a NASA sounding rocket and collected the highest spatial resolution images ever obtained of the solar corona. One of the goals of the Hi-C flight was to characterize the substructure of the solar corona. We therefore calculate how the intensity scales from a low-resolution (AIA) pixels to high-resolution (Hi-C) pixels for both the dynamic events and "background" emission (meaning, the steady emission over the 5 minutes of data acquisition time). We find there is no evidence of substructure in the background corona; the intensity scales smoothly from low-resolution to high-resolution Hi-C pixels. In transient events, however, the intensity observed with Hi-C is, on average, 2.6 times larger than observed with AIA. This increase in intensity suggests that AIA is not resolving these events. This result suggests a finely structured dynamic corona embedded in a smoothly varying background.

  16. Reheating effects in the matter power spectrum and implications for substructure

    SciTech Connect

    Erickcek, Adrienne L.; Sigurdson, Kris

    2011-10-15

    The thermal and expansion history of the Universe before big bang nucleosynthesis is unknown. We investigate the evolution of cosmological perturbations through the transition from an early matter era to radiation domination. We treat reheating as the perturbative decay of an oscillating scalar field into relativistic plasma and cold dark matter. After reheating, we find that subhorizon perturbations in the decay-produced dark matter density are significantly enhanced, while subhorizon radiation perturbations are instead suppressed. If dark matter originates in the radiation bath after reheating, this suppression may be the primary cutoff in the matter power spectrum. Conversely, for dark matter produced nonthermally from scalar decay, enhanced perturbations can drive structure formation during the cosmic dark ages and dramatically increase the abundance of compact substructures. For low reheat temperatures, we find that as much as 50% of all dark matter is in microhalos with M > or approx. 0.1M{sub +} at z{approx_equal}100, compared to a fraction of {approx}10{sup -10} in the standard case. In this scenario, ultradense substructures may constitute a large fraction of dark matter in galaxies today.

  17. Dark matter constraints from the Fermi/LAT Extragalactic Gamma-ray Background and the role of halo substructure

    NASA Astrophysics Data System (ADS)

    Sanchez-Conde, Miguel Angel

    2012-05-01

    After almost four years of operation, Fermi/LAT has measured the Extragalactic Gamma-ray Background (EGB) with unprecedented sensitivity, furthermore extending, for the first time, the EGB spectrum down to 100 MeV and up to several hundred GeV. Although a large variety of extragalactic objects are expected to contribute to the EGB, according to recent estimates the sum of their different contributions is not enough to explain the measured EGB. Gamma-rays from annihilation products of supersymmetric dark matter (DM) particles may account for this missing emission. In this talk, I will discuss on the parameter space allowed for DM annihilation in the most recent EGB spectrum by Fermi/LAT. At present, the key ingredient in the determination of the expected contribution of DM annihilation to the EGB is the so-called substructure boost factor, thus special attention will be given to this parameter. Substructure boosts are related to the amount of DM subhalos hosted by larger DM halos. Up to now, attempts to precisely calculate it both analytically and/or making use of N-body cosmological simulations have failed due to the difficulty of examining in detail the properties of the smallest DM halos. Indeed, the DM contribution to the EGB can vary over several orders of magnitude depending on the assumed DM substructure model. Here, I will present a DM substructure model which is based on our current knowledge of DM halo formation and evolution in the framework of the state-of-the-art ΛCDM cosmological model. This model makes possible to confidently calculate substructure boosts for halos of different masses. After applying it, the uncertainty bands that bracket the contribution of DM annihilation to the EGB will become not only substantially narrower but also better physically motivated. The use of such a more sophisticated DM substructure model makes possible to assess other crucial EGB aspects as well.

  18. Making the Common Good Common

    ERIC Educational Resources Information Center

    Chase, Barbara

    2011-01-01

    How are independent schools to be useful to the wider world? Beyond their common commitment to educate their students for meaningful lives in service of the greater good, can they educate a broader constituency and, thus, share their resources and skills more broadly? Their answers to this question will be shaped by their independence. Any…

  19. Superposed epoch study of ICME sub-structures near Earth and their effects on Galactic cosmic rays

    NASA Astrophysics Data System (ADS)

    Masías-Meza, J. J.; Dasso, S.; Démoulin, P.; Rodriguez, L.; Janvier, M.

    2016-08-01

    Context. Interplanetary coronal mass ejections (ICMEs) are the interplanetary manifestations of solar eruptions. The overtaken solar wind forms a sheath of compressed plasma at the front of ICMEs. Magnetic clouds (MCs) are a subset of ICMEs with specific properties (e.g. the presence of a flux rope). When ICMEs pass near Earth, ground observations indicate that the flux of Galactic cosmic rays (GCRs) decreases. Aims: The main aims of this paper are to find common plasma and magnetic properties of different ICME sub-structures and which ICME properties affect the flux of GCRs near Earth. Methods: We used a superposed epoch method applied to a large set of ICMEs observed in situ by the spacecraft ACE, between 1998 and 2006. We also applied a superposed epoch analysis on GCRs time series observed with the McMurdo neutron monitors. Results: We find that slow MCs at 1 AU have on average more massive sheaths. We conclude that this is because they are more effectively slowed down by drag during their travel from the Sun. Slow MCs also have a more symmetric magnetic field and sheaths expanding similarly as their following MC, while in contrast, fast MCs have an asymmetric magnetic profile and a sheath in compression. In all types of MCs, we find that the proton density and the temperature and the magnetic fluctuations can diffuse within the front of the MC due to 3D reconnection. Finally, we derive a quantitative model that describes the decrease in cosmic rays as a function of the amount of magnetic fluctuations and field strength. Conclusions: The obtained typical profiles of sheath, MC and GCR properties corresponding to slow, middle, and fast ICMEs, can be used for forecasting or modelling these events, and to better understand the transport of energetic particles in ICMEs. They are also useful for improving future operative space weather activities.

  20. Within-Population Genetic Structure in Beech (Fagus sylvatica L.) Stands Characterized by Different Disturbance Histories: Does Forest Management Simplify Population Substructure?

    PubMed Central

    Piotti, Andrea; Leonardi, Stefano; Heuertz, Myriam; Buiteveld, Joukje; Geburek, Thomas; Gerber, Sophie; Kramer, Koen; Vettori, Cristina; Vendramin, Giovanni Giuseppe

    2013-01-01

    The fine-scale assessment of both spatially and non-spatially distributed genetic variation is crucial to preserve forest genetic resources through appropriate forest management. Cryptic within-population genetic structure may be more common than previously thought in forest tree populations, which has strong implications for the potential of forests to adapt to environmental change. The present study was aimed at comparing within-population genetic structure in European beech (Fagus sylvatica L.) plots experiencing different disturbance levels. Five plot pairs made up by disturbed and undisturbed plots having the same biogeographic history were sampled throughout Europe. Overall, 1298 individuals were analyzed using four highly polymorphic nuclear microsatellite markers (SSRs). Bayesian clustering within plots identified 3 to 11 genetic clusters (within-plot θST ranged from 0.025 to 0.124). The proportion of within-population genetic variation due to genetic substructuring (FCluPlot = 0.067) was higher than the differentiation among the 10 plots (FPlotTot = 0.045). Focusing on the comparison between managed and unmanaged plots, disturbance mostly explains differences in the complexity of within-population genetic structure, determining a reduction of the number of genetic clusters present in a standardized area. Our results show that: i) genetic substructuring needs to be investigated when studying the within-population genetic structure in forest tree populations, and ii) indices describing subtle characteristics of the within-population genetic structure are good candidates for providing early signals of the consequences of forest management, and of disturbance events in general. PMID:24039930

  1. Revealing substructures of H4 and H5 hole traps in p-type InP using Laplace deep-level transient spectroscopy

    SciTech Connect

    Darwich, R.; Mani, A. A.

    2010-08-15

    New substructures of H4 and H5 hole traps have been revealed using Laplace deep-level transient spectroscopy. Our measurements show that the hole traps H4 and H5 can have at least three components for each. Moreover, the activation energies are deduced and the microscopic nature of these substructures is discussed.

  2. Boosted objects and jet substructure at the LHC: Report of BOOST2012, held at IFIC Valencia, 23rd-27th of July 2012

    DOE PAGES

    Altheimer, A.

    2014-03-21

    This report of the BOOST2012 workshop presents the results of four working groups that studied key aspects of jet substructure. We discuss the potential of first-principle QCD calculations to yield a precise description of the substructure of jets and study the accuracy of state-of-the-art Monte Carlo tools. Limitations of the experiments’ ability to resolve substructure are evaluated, with a focus on the impact of additional (pile-up) proton proton collisions on jet substructure performance in future LHC operating scenarios. The final section summarizes the lessons learnt from jet substructure analyses in searches for new physics in the production of boosted topmore » quarks.« less

  3. Preparation and in vivo evaluation of linkers for 211At labeling of humanized anti-Tac.

    PubMed

    Yordanov, A T; Garmestani, K; Zhang, M; Zhang, Z; Yao, Z; Phillips, K E; Herring, B; Horak, E; Beitzel, M P; Schwarz, U P; Gansow, O A; Plascjak, P S; Eckelman, W C; Waldmann, T A; Brechbiel, M W

    2001-10-01

    The syntheses, radiolabeling, antibody conjugation, and in vivo evaluation of new linkers for 211At labeling of humanized anti-Tac (Hu-anti-Tac), an antibody to the alpha-chain of the IL-2 receptor (IL-2Ralpha) shown to be a useful target for radioimmunotherapy are described. Synthesis of the organometallic linker precursors is accomplished by reaction of the corresponding bromo- or iodoaryl esters with bis(tributyltin) in the presence of a palladium catalyst. Subsequent conversion to the corresponding N-succinimidyl ester and labeling with 211At of two new linkers, N-succinimidyl 4-[211At]astato-3-methylbenzoate and N-succinimidyl N-(4-[211At]astatophenethyl)succinamate (SAPS), together with the previously reported N-succinimidyl 4-[211At]astatobenzoate and N-succinimidyl 3-[211At]astato-4-methylbenzoate, are each conjugated to Hu-anti-Tac. The plasma survival times of these conjugates are compared to those of directly iodinated (125I) Hu-anti-Tac. The N-succinimidyl N-(4-[211At]astatophenethyl)succinamate compound (SAPS) emerged from this assay as the most viable candidate for 211At-labeling of Hu-anti-Tac. SAPS, along with the directly analogous radio-iodinated reagent, N-succinimidyl N-(4-[125I]astatophenethyl)succinamate (SIPS), are evaluated in a biodistribution study along with directly iodinated (125I) Hu-anti-Tac. Blood clearance and biological accretion results indicate that SAPS is a viable candidate for further evaluation for radioimmunotherapy of cancer.

  4. Small angle x-ray scattering of chromatin. Radius and mass per unit length depend on linker length

    SciTech Connect

    Williams, S.P.; Langmore, J.P. )

    1991-03-01

    Analyses of low angle x-ray scattering from chromatin, isolated by identical procedures but from different species, indicate that fiber diameter and number of nucleosomes per unit length increase with the amount of nucleosome linker DNA. Experiments were conducted at physiological ionic strength to obtain parameters reflecting the structure most likely present in living cells. Guinier analyses were performed on scattering from solutions of soluble chromatin from Necturus maculosus erythrocytes (linker length 48 bp), chicken erythrocytes (linker length 64 bp), and Thyone briareus sperm (linker length 87 bp). The results were extrapolated to infinite dilution to eliminate interparticle contributions to the scattering. Cross-sectional radii of gyration were found to be 10.9 {plus minus} 0.5, 12.1 {plus minus} 0.4, and 15.9 {plus minus} 0.5 nm for Necturus, chicken, and Thyone chromatin, respectively, which are consistent with fiber diameters of 30.8, 34.2, and 45.0 nm. Mass per unit lengths were found to be 6.9 {plus minus} 0.5, 8.3 {plus minus} 0.6, and 11.8 {plus minus} 1.4 nucleosomes per 10 nm for Necturus, chicken, and Thyone chromatin, respectively. The geometrical consequences of the experimental mass per unit lengths and radii of gyration are consistent with a conserved interaction among nucleosomes. Cross-linking agents were found to have little effect on fiber external geometry, but significant effect on internal structure. The absolute values of fiber diameter and mass per unit length, and their dependencies upon linker length agree with the predictions of the double-helical crossed-linker model. A compilation of all published x-ray scattering data from the last decade indicates that the relationship between chromatin structure and linker length is consistent with data obtained by other investigators.

  5. Dynamics of linker residues modulate the nucleic acid binding properties of the HIV-1 nucleocapsid protein zinc fingers.

    PubMed

    Zargarian, Loussiné; Tisné, Carine; Barraud, Pierre; Xu, Xiaoqian; Morellet, Nelly; René, Brigitte; Mély, Yves; Fossé, Philippe; Mauffret, Olivier

    2014-01-01

    The HIV-1 nucleocapsid protein (NC) is a small basic protein containing two zinc fingers (ZF) separated by a short linker. It is involved in several steps of the replication cycle and acts as a nucleic acid chaperone protein in facilitating nucleic acid strand transfers occurring during reverse transcription. Recent analysis of three-dimensional structures of NC-nucleic acids complexes established a new property: the unpaired guanines targeted by NC are more often inserted in the C-terminal zinc finger (ZF2) than in the N-terminal zinc finger (ZF1). Although previous NMR dynamic studies were performed with NC, the dynamic behavior of the linker residues connecting the two ZF domains remains unclear. This prompted us to investigate the dynamic behavior of the linker residues. Here, we collected 15N NMR relaxation data and used for the first time data at several fields to probe the protein dynamics. The analysis at two fields allows us to detect a slow motion occurring between the two domains around a hinge located in the linker at the G35 position. However, the amplitude of motion appears limited in our conditions. In addition, we showed that the neighboring linker residues R29, A30, P31, R32, K33 displayed restricted motion and numerous contacts with residues of ZF1. Our results are fully consistent with a model in which the ZF1-linker contacts prevent the ZF1 domain to interact with unpaired guanines, whereas the ZF2 domain is more accessible and competent to interact with unpaired guanines. In contrast, ZF1 with its large hydrophobic plateau is able to destabilize the double-stranded regions adjacent to the guanines bound by ZF2. The linker residues and the internal dynamics of NC regulate therefore the different functions of the two zinc fingers that are required for an optimal chaperone activity.

  6. The DEK1 Calpain Linker Functions in Three-Dimensional Body Patterning in Physcomitrella patens1[OPEN

    PubMed Central

    Demko, Viktor; Mekhlif, Ahmed Khaleel

    2016-01-01

    The DEFECTIVE KERNEL1 (DEK1) calpain is a conserved 240-kD key regulator of three-dimensional body patterning in land plants acting via mitotic cell plane positioning. The activity of the cytosolic C-terminal calpain protease is regulated by the membrane-anchored DEK1 MEM, which is connected to the calpain via the 600-amino acid residue Linker. Similar to the calpain and MEM domains, the Linker is highly conserved in the land plant lineage, the similarity dropping sharply compared with orthologous charophyte sequences. Using site-directed mutagenesis, we studied the effect on Physcomitrella patens development by deleting the Linker and two conserved Linker motifs. The results show that removal of the Linker has nearly the same effect as removal of the entire DEK1 gene. In contrast, deletion of the conserved Laminin_G3 (LG3) domain had a milder effect, perturbing leafy gametophore patterning and archegonia development. The LG3 domain from Marchantia polymorpha is fully functional in P. patens, whereas angiosperm sequences are not functional. Deletion of a C-terminal Linker subsegment containing a potential calpain autolytic site severely disturbs gametophore development. Finally, changing one of the three calpain active-site amino acid residues results in the same phenotype as deleting the entire DEK1 gene. Based on the conserved nature of animal and DEK1 calpains, we propose that the DEK1 MEM-Linker complex inactivates the calpain by forcing apart the two calpain subunits carrying the three amino acids of the active site. PMID:27506240

  7. Design of antiviral stapled peptides containing a biphenyl cross-linker.

    PubMed

    Muppidi, Avinash; Zhang, Hongtao; Curreli, Francesca; Li, Nan; Debnath, Asim K; Lin, Qing

    2014-04-01

    Here we report the design and synthesis of a panel of stapled peptides containing a distance-matching biphenyl cross-linker based upon a peptide capsid assembly inhibitor reported previously. Compared with the linear peptide, the biphenyl-stapled peptides exhibited significantly enhanced cell penetration and potent antiviral activity in the cell-based infection assays. Isothermal titration calorimetry and surface plasmon resonance experiments revealed that the most active stapled CAI peptide binds to the C-terminal domain of HIV capsid protein as well as envelop glycoprotein gp120 with low micromolar binding affinities, and as a result, inhibits both the HIV-1 virus entry and the virus assembly.

  8. Cross-Linker Unbinding and Self-Similarity in Bundled Cytoskeletal Networks

    NASA Astrophysics Data System (ADS)

    Lieleg, O.; Bausch, A. R.

    2007-10-01

    The macromechanical properties of purely bundled in vitro actin networks are not only determined by the micromechanical properties of individual bundles but also by molecular unbinding events of the actin-binding protein (ABP) fascin. Under high mechanical load the network elasticity depends on the forced unbinding of individual ABPs in a rate dependent manner. Cross-linker unbinding in combination with the structural self-similarity of the network enables the introduction of a concentration-time superposition principle—broadening the mechanically accessible frequency range over 8 orders of magnitude.

  9. A push-pull organic dye with a quinoidal thiophene linker: Photophysical properties and solvent effects

    NASA Astrophysics Data System (ADS)

    Climent, Clàudia; Carreras, Abel; Alemany, Pere; Casanova, David

    2016-10-01

    In the present work we perform a computational study of the properties of a push-pull organic dye with a quinoidal thiophene unit as the conjugated linker between the electron donor and acceptor groups. We investigate the photophysical properties of the dye related to its potential use as a molecular sensitizer in dye-sensitized solar cells. We rationalize the solvation effects on the absorption band of the dye in protic and aprotic solvents, identifying the interaction of alcohol solvents with the amine in the donor group as the source for the blue shift of the absorption band with respect to aprotic solvents.

  10. Clickable tyrosine binding bifunctional linkers for preparation of DNA-protein conjugates.

    PubMed

    Bauer, Dennis M; Ahmed, Ishtiaq; Vigovskaya, Antonina; Fruk, Ljiljana

    2013-06-19

    We have prepared bifunctional linkers containing clickable functional groups that enable preparation of protein-DNA conjugates through binding onto tyrosine residues. Mild conjugation strategy was demonstrated using two proteins, streptavidin(STV) and myoglobin (Mb) and it resulted in conjugates with preserved functionality of both the proteins and DNA strands. Furthermore, we show that protein-DNA conjugates can be successfully immobilized onto solid surface containing complementary DNA strands and the enzymatic activity of Mb-DNA conjugates is even higher than that of corresponding conjugates prepared through Lys binding.

  11. Effects of modifications of the linker in a series of phenylpropanoic acid derivatives: Synthesis, evaluation as PPARalpha/gamma dual agonists, and X-ray crystallographic studies.

    PubMed

    Casimiro-Garcia, Agustin; Bigge, Christopher F; Davis, Jo Ann; Padalino, Teresa; Pulaski, James; Ohren, Jeffrey F; McConnell, Patrick; Kane, Christopher D; Royer, Lori J; Stevens, Kimberly A; Auerbach, Bruce J; Collard, Wendy T; McGregor, Christine; Fakhoury, Stephen A; Schaum, Robert P; Zhou, Hairong

    2008-05-01

    A new series of alpha-aryl or alpha-heteroarylphenyl propanoic acid derivatives was synthesized that incorporate acetylene-, ethylene-, propyl-, or nitrogen-derived linkers as a replacement of the commonly used ether moiety that joins the central phenyl ring with the lipophilic tail. The effect of these modifications in the binding and activation of PPARalpha and PPARgamma was first evaluated in vitro. Compounds possessing suitable profiles were then evaluated in the ob/ob mouse model of type 2 diabetes. The propylene derivative 40 and the propyl derivative 53 demonstrated robust plasma glucose lowering activity in this model. Compound 53 was also evaluated in male Zucker diabetic fatty rats and was found to achieve normalization of glucose, triglycerides, and insulin levels. An X-ray crystal structure of the complex of 53 with the PPARgamma-ligand-binding domain was obtained and discussed in this report.

  12. What (if anything) can few-body strange systems teach us about quark-gluon hadronic substructure

    SciTech Connect

    Maltman, K. . Dept. of Physics Los Alamos National Lab., NM )

    1990-01-01

    We discuss expectation, relevant to the proposed ({pi},K) program at PILAC, for the effects of hadronic quark-gluon substructure on the physics of few-body strangeness {minus}1 systems, in the context of QCD-inspired models used previously to describe the hadron spectrum and short distance nucleon-nucleon scattering. 50 refs., 2 tabs.

  13. Substructure analysis using NICE/SPAR and applications of force to linear and nonlinear structures. [spacecraft masts

    NASA Technical Reports Server (NTRS)

    Razzaq, Zia; Prasad, Venkatesh; Darbhamulla, Siva Prasad; Bhati, Ravinder; Lin, Cai

    1987-01-01

    Parallel computing studies are presented for a variety of structural analysis problems. Included are the substructure planar analysis of rectangular panels with and without a hole, the static analysis of space mast, using NICE/SPAR and FORCE, and substructure analysis of plane rigid-jointed frames using FORCE. The computations are carried out on the Flex/32 MultiComputer using one to eighteen processors. The NICE/SPAR runstream samples are documented for the panel problem. For the substructure analysis of plane frames, a computer program is developed to demonstrate the effectiveness of a substructuring technique when FORCE is enforced. Ongoing research activities for an elasto-plastic stability analysis problem using FORCE, and stability analysis of the focus problem using NICE/SPAR are briefly summarized. Speedup curves for the panel, the mast, and the frame problems provide a basic understanding of the effectiveness of parallel computing procedures utilized or developed, within the domain of the parameters considered. Although the speedup curves obtained exhibit various levels of computational efficiency, they clearly demonstrate the excellent promise which parallel computing holds for the structural analysis problem. Source code is given for the elasto-plastic stability problem and the FORCE program.

  14. REPORT TO THE NATIONAL SCIENCE FOUNDATION ON THE SUBSTRUCTURE SEARCH DEMONSTRATION CONDUCTED IN NEW YORK CITY SEPTEMBER 1966.

    ERIC Educational Resources Information Center

    American Chemical Society, Columbus, OH. Chemical Abstracts Service.

    CHEMICAL ABSTRACTS SERVICE (CAS), IN CONJUNCTION WITH THE NATIONAL SCIENCE FOUNDATION, CONDUCTED THE FIRST PUBLIC DEMONSTRATION OF CAS COMPUTER-BASED SUBSTRUCTURE SEARCH TECHNIQUES AT THE 152ND MEETING OF THE AMERICAN CHEMICAL SOCIETY IN NEW YORK CITY. FROM SEPTEMBER 11 THROUGH SEPTEMBER 16, 1966, INTERESTED PERSONS WERE GIVEN THE OPPORTUNITY TO…

  15. The Genetics of Mexico Recapitulates Native American Substructure and Affects Biomedical Traits

    PubMed Central

    Moreno-Estrada, Andrés; Gignoux, Christopher R.; Fernández-López, Juan Carlos; Zakharia, Fouad; Sikora, Martin; Contreras, Alejandra V.; Acuña-Alonzo, Victor; Sandoval, Karla; Eng, Celeste; Romero-Hidalgo, Sandra; Ortiz-Tello, Patricia; Robles, Victoria; Kenny, Eimear E.; Nuño-Arana, Ismael; Barquera-Lozano, Rodrigo; Macín-Pérez, Gastón; Granados-Arriola, Julio; Huntsman, Scott; Galanter, Joshua M.; Via, Marc; Ford, Jean G.; Chapela, Rocío; Rodriguez-Cintron, William; Rodríguez-Santana, Jose R.; Romieu, Isabelle; Sienra-Monge, Juan José; Navarro, Blanca del Rio; London, Stephanie J.; Ruiz-Linares, Andrés; Garcia-Herrera, Rodrigo; Estrada, Karol; Hidalgo-Miranda, Alfredo; Jimenez-Sanchez, Gerardo; Carnevale, Alessandra; Soberón, Xavier; Canizales-Quinteros, Samuel; Rangel-Villalobos, Héctor; Silva-Zolezzi, Irma; Burchard, Esteban Gonzalez; Bustamante, Carlos D.

    2014-01-01

    Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1,000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between sub-continental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide. PMID:24926019

  16. ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure.

    PubMed

    Jain, Saumya; Wheeler, Joshua R; Walters, Robert W; Agrawal, Anurag; Barsic, Anthony; Parker, Roy

    2016-01-28

    Stress granules are mRNA-protein granules that form when translation initiation is limited, and they are related to pathological granules in various neurodegenerative diseases. Super-resolution microscopy reveals stable substructures, referred to as cores, within stress granules that can be purified. Proteomic analysis of stress granule cores reveals a dense network of protein-protein interactions and links between stress granules and human diseases and identifies ATP-dependent helicases and protein remodelers as conserved stress granule components. ATP is required for stress granule assembly and dynamics. Moreover, multiple ATP-driven machines affect stress granules differently, with the CCT complex inhibiting stress granule assembly, while the MCM and RVB complexes promote stress granule persistence. Our observations suggest that stress granules contain a stable core structure surrounded by a dynamic shell with assembly, disassembly, and transitions between the core and shell modulated by numerous protein and RNA remodeling complexes.

  17. Human genetics. The genetics of Mexico recapitulates Native American substructure and affects biomedical traits.

    PubMed

    Moreno-Estrada, Andrés; Gignoux, Christopher R; Fernández-López, Juan Carlos; Zakharia, Fouad; Sikora, Martin; Contreras, Alejandra V; Acuña-Alonzo, Victor; Sandoval, Karla; Eng, Celeste; Romero-Hidalgo, Sandra; Ortiz-Tello, Patricia; Robles, Victoria; Kenny, Eimear E; Nuño-Arana, Ismael; Barquera-Lozano, Rodrigo; Macín-Pérez, Gastón; Granados-Arriola, Julio; Huntsman, Scott; Galanter, Joshua M; Via, Marc; Ford, Jean G; Chapela, Rocío; Rodriguez-Cintron, William; Rodríguez-Santana, Jose R; Romieu, Isabelle; Sienra-Monge, Juan José; del Rio Navarro, Blanca; London, Stephanie J; Ruiz-Linares, Andrés; Garcia-Herrera, Rodrigo; Estrada, Karol; Hidalgo-Miranda, Alfredo; Jimenez-Sanchez, Gerardo; Carnevale, Alessandra; Soberón, Xavier; Canizales-Quinteros, Samuel; Rangel-Villalobos, Héctor; Silva-Zolezzi, Irma; Burchard, Esteban Gonzalez; Bustamante, Carlos D

    2014-06-13

    Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide.

  18. Hints of Thermal Fragmentation in the Primordial Substructure of NGC2264

    NASA Astrophysics Data System (ADS)

    Teixeira, P. S.; Lada, C. J.; Young, E. T.; Marengo, M.; Muench, A.; Muzerolle, J.; Siegler, N.; Rieke, G.; Hartmann, L.; Megeath, T.; Fazio, G.

    2005-12-01

    We present Spitzer observations of a young star forming region within NGC2264. These observations reveal new 24 micron sources in curious linear alignments, extending radially like spokes on a wheel from a previously known luminous young protostar. These 24 micron sources are found to be mostly ( ˜60%) Class I protostars that are highly embedded within dense filamentary molecular material. The protostars still retain the primordial substructuring of the parental cloud. We find the protostars to be separated by regular intervals that are consistent with the Jeans length for the average density of the associated molecular material, suggesting that thermal fragmentation played an important role during the star forming process in this region. The figure shows a false color image of this young region built from MIPS 24 micron (red), IRAC 8 micron (green), and IRAC 3.6 micron (blue) data. PT acknowledges support from the scholarship SFRH/BD/13984/2003 FCT, Portugal.

  19. Application of Frequency Domain Substructure Synthesis Technique for Plates Loaded with Complex Attachments

    SciTech Connect

    RL Campbell; SA Hambric

    2004-02-05

    Frequency domain substructure synthesis is a modeling technique that enables the prediction of a combined response of individual structures using experimentally measured or numerically predicted frequency response functions (FRFs). The traditional synthesis algorithm [1,2] operates on component impedances and thus generally requires several matrix inversions. An improved algorithm, developed by Jetmundsen et al. [3], requires a single matrix inversion with a completely arbitrary interface definition that can easily incorporate connection impedances. The main limitations of the method are the large data requirements and sensitivity to data truncation. The utility of this technique is demonstrated through a comparison of synthesized and measured admittances of an edge-stiffened plate with attached equipment. The plate mobilities are obtained from a numerical analysis because of the ability to accurately model this structure using a finite element representation. The attachments are characterized experimentally because of their complexity. The sections describe the synthesis technique and show numerical and experimental results for the plate and equipment.

  20. Extended stellar substructure surrounding the Boötes I dwarf spheroidal galaxy

    NASA Astrophysics Data System (ADS)

    Roderick, T. A.; Mackey, A. D.; Jerjen, H.; Da Costa, G. S.

    2016-10-01

    We present deep stellar photometry of the Boötes I dwarf spheroidal galaxy in g- and i-band filters, taken with the Dark Energy Camera at Cerro Tololo in Chile. Our analysis reveals a large, extended region of stellar substructure surrounding the dwarf, as well as a distinct overdensity encroaching on its tidal radius. A radial profile of the Boötes I stellar distribution shows a break radius indicating the presence of extra-tidal stars. These observations strongly suggest that Boötes I is experiencing tidal disruption, although not as extreme as that exhibited by the Hercules dwarf spheroidal. Combined with revised velocity dispersion measurements from the literature, we see evidence suggesting the need to review previous theoretical models of the Boötes I dwarf spheroidal galaxy.

  1. A model for Quick Load Analysis for monopile-type offshore wind turbine substructures

    NASA Astrophysics Data System (ADS)

    Schløer, Signe; Garcia Castillo, Laura; Fejerskov, Morten; Stroescu, Emanuel; Bredmose, Henrik

    2016-09-01

    A model for Quick Load Analysis, QuLA, of an offshore wind turbine substructure is presented. The aerodynamic rotor loads and damping are precomputed for a load-based configuration. The dynamic structural response is represented by the first global fore-aft mode only and is computed in the frequency domain using the equation of motion. The model is compared against the state of the art aeroelastic code, Flex5, and both life time fatigue and extreme loads are considered in the comparison. In general there is good similarity between the two models. Some derivation for the sectional forces are explained in terms of the model simplifications. The difference in the sectional moments are found to be within 14% for the fatigue load case and 10% for the extreme load condition.

  2. Improving LHC searches for dark photons using lepton-jet substructure

    NASA Astrophysics Data System (ADS)

    Barello, G.; Chang, Spencer; Newby, Christopher A.; Ostdiek, Bryan

    2017-03-01

    Collider signals of dark photons are an exciting probe for new gauge forces and are characterized by events with boosted lepton jets. Existing techniques are efficient in searching for muonic lepton jets but due to substantial backgrounds have difficulty constraining lepton jets containing only electrons. This is unfortunate since upcoming intensity frontier experiments are sensitive to dark photon masses which only allow electron decays. Analyzing a recently proposed model of kinetic mixing, with new scalar particles decaying into dark photons, we find that existing techniques for electron jets can be substantially improved. We show that using lepton-jet-substructure variables, in association with a boosted decision tree, improves background rejection, significantly increasing the LHC's reach for dark photons in this region of parameter space.

  3. Chemical Abundances of Planetary Nebulae in the Substructures of M31

    NASA Astrophysics Data System (ADS)

    Fang, Xuan; García-Benito, Rubén; Guerrero, Martín A.; Liu, Xiaowei; Yuan, Haibo; Zhang, Yong; Zhang, Bing

    2015-12-01

    We present deep spectroscopy of planetary nebulae (PNe) that are associated with the substructures of the Andromeda Galaxy (M31). The spectra were obtained with the Optical System for Imaging and low-intermediate-Resolution Integrated Spectroscopy spectrograph on the 10.4 m Gran Telescopio Canarias. Seven targets were selected for the observations, three in the Northern Spur and four associated with the Giant Stream. The most distant target in our sample, with a rectified galactocentric distance ≥slant 100 kpc, was the first PN discovered in the outer streams of M31. The [O iii] λ4363 auroral line is well detected in the spectra of all targets, enabling electron temperature determination. Ionic abundances are derived based on the [O iii] temperatures, and elemental abundances of helium, nitrogen, oxygen, neon, sulfur, and argon are estimated. The relatively low N/O and He/H ratios, as well as abundance ratios of α-elements, indicate that our target PNe might belong to populations as old as ∼2 Gyr. Our PN sample, including the current seven and the previous three observed by Fang et al., have rather homogeneous oxygen abundances. The study of abundances and the spatial and kinematical properties of our sample leads to the tempting conclusion that their progenitors might belong to the same stellar population, which hints at a possibility that the Northern Spur and the Giant Stream have the same origin. This may be explained by the stellar orbit proposed by Merrett et al. Judging from the position and kinematics, we emphasize that M32 might be responsible for the two substructures. Deep spectroscopy of PNe in M32 will help to assess this hypothesis. Based on observations made with the Gran Telescopio Canarias, installed at the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias, in the island of La Palma. These observations are associated with program No. GTC55-14B.

  4. Ancient substructure in early mtDNA lineages of southern Africa.

    PubMed

    Barbieri, Chiara; Vicente, Mário; Rocha, Jorge; Mpoloka, Sununguko W; Stoneking, Mark; Pakendorf, Brigitte

    2013-02-07

    Among the deepest-rooting clades in the human mitochondrial DNA (mtDNA) phylogeny are the haplogroups defined as L0d and L0k, which are found primarily in southern Africa. These lineages are typically present at high frequency in the so-called Khoisan populations of hunter-gatherers and herders who speak non-Bantu languages, and the early divergence of these lineages led to the hypothesis of ancient genetic substructure in Africa. Here we update the phylogeny of the basal haplogroups L0d and L0k with 500 full mtDNA genome sequences from 45 southern African Khoisan and Bantu-speaking populations. We find previously unreported subhaplogroups and greatly extend the amount of variation and time-depth of most of the known subhaplogroups. Our major finding is the definition of two ancient sublineages of L0k (L0k1b and L0k2) that are present almost exclusively in Bantu-speaking populations from Zambia; the presence of such relic haplogroups in Bantu speakers is most probably due to contact with ancestral pre-Bantu populations that harbored different lineages than those found in extant Khoisan. We suggest that although these populations went extinct after the immigration of the Bantu-speaking populations, some traces of their haplogroup composition survived through incorporation into the gene pool of the immigrants. Our findings thus provide evidence for deep genetic substructure in southern Africa prior to the Bantu expansion that is not represented in extant Khoisan populations.

  5. THE NEXT GENERATION VIRGO CLUSTER SURVEY. XIX. TOMOGRAPHY OF MILKY WAY SUBSTRUCTURES IN THE NGVS FOOTPRINT

    SciTech Connect

    Lokhorst, Deborah; Starkenburg, Else; Navarro, Julio F.; McConnachie, Alan W.; Ferrarese, Laura; Côté, Patrick; Gwyn, Stephen D. J.; Liu, Chengze; Peng, Eric W.; Cuillandre, Jean-Charles

    2016-03-10

    The Next Generation Virgo Cluster Survey (NGVS) is a deep u*giz survey targeting the Virgo Cluster of galaxies at 16.5 Mpc. This survey provides high-quality photometry over an ∼100 deg{sup 2} region straddling the constellations of Virgo and Coma Berenices. This sightline through the Milky Way is noteworthy in that it intersects two of the most prominent substructures in the Galactic halo: the Virgo overdensity (VOD) and Sagittarius stellar stream (close to its bifurcation point). In this paper, we use deep u*gi imaging from the NGVS to perform tomography of the VOD and Sagittarius stream using main-sequence turnoff (MSTO) stars as a halo tracer population. The VOD, whose centroid is known to lie at somewhat lower declinations (α ∼ 190°, δ ∼ −5°) than is covered by the NGVS, is nevertheless clearly detected in the NGVS footprint at distances between ∼8 and 25 kpc. By contrast, the Sagittarius stream is found to slice directly across the NGVS field at distances between 25 and 40 kpc, with a density maximum at ≃35 kpc. No evidence is found for new substructures beyond the Sagittarius stream, at least out to a distance of ∼90 kpc—the largest distance to which we can reliably trace the halo using MSTO stars. We find clear evidence for a distance gradient in the Sagittarius stream across the ∼30° of sky covered by the NGVS and its flanking fields. We compare our distance measurements along the stream with those predicted by leading stream models.

  6. DNA identification by pedigree likelihood ratio accommodating population substructure and mutations

    PubMed Central

    2010-01-01

    DNA typing is an important tool in missing-person identification, especially in mass-fatality disasters. Identification methods comparing a DNA profile from unidentified human remains with that of a direct (from the person) or indirect (for example, from a biological relative) reference sample and ranking the pairwise likelihood ratios (LR) is straightforward and well defined. However, for indirect comparison cases in which several members from a family can serve as reference samples, the full power of kinship analysis is not entirely exploited. Because biologically related family members are not genetically independent, more information and thus greater power can be attained by simultaneous use of all pedigree members in most cases, although distant relationships may reduce the power. In this study, an improvement was made on the method for missing-person identification for autosomal and lineage-based markers, by considering jointly the DNA profile data of all available family reference samples. The missing person is evaluated by a pedigree LR of the probability of DNA evidence under alternative hypotheses (for example, the missing person is unrelated or if they belong to this pedigree with a specified biological relationship) and can be ranked for all pedigrees within a database. Pedigree LRs are adjusted for population substructure according to the recommendations of the second National Research Council (NRCII) Report. A realistic mutation model was also incorporated to accommodate the possibility of false exclusion. The results show that the effect of mutation on the pedigree LR is moderate, but LRs can be significantly decreased by the effect of population substructure. Finally, Y chromosome and mitochondrial DNA were integrated into the analysis to increase the power of identification. A program titled MPKin was developed, combining the aforementioned features to facilitate genetic analysis for identifying missing persons. The computational complexity of the

  7. The Next Generation Virgo Cluster Survey. XIX. Tomography of Milky Way Substructures in the NGVS Footprint

    NASA Astrophysics Data System (ADS)

    Lokhorst, Deborah; Starkenburg, Else; McConnachie, Alan W.; Navarro, Julio F.; Ferrarese, Laura; Côté, Patrick; Liu, Chengze; Peng, Eric W.; Gwyn, Stephen D. J.; Cuillandre, Jean-Charles; Guhathakurta, Puragra

    2016-03-01

    The Next Generation Virgo Cluster Survey (NGVS) is a deep u*giz survey targeting the Virgo Cluster of galaxies at 16.5 Mpc. This survey provides high-quality photometry over an ˜100 deg2 region straddling the constellations of Virgo and Coma Berenices. This sightline through the Milky Way is noteworthy in that it intersects two of the most prominent substructures in the Galactic halo: the Virgo overdensity (VOD) and Sagittarius stellar stream (close to its bifurcation point). In this paper, we use deep u*gi imaging from the NGVS to perform tomography of the VOD and Sagittarius stream using main-sequence turnoff (MSTO) stars as a halo tracer population. The VOD, whose centroid is known to lie at somewhat lower declinations (α ˜ 190°, δ ˜ -5°) than is covered by the NGVS, is nevertheless clearly detected in the NGVS footprint at distances between ˜8 and 25 kpc. By contrast, the Sagittarius stream is found to slice directly across the NGVS field at distances between 25 and 40 kpc, with a density maximum at ≃35 kpc. No evidence is found for new substructures beyond the Sagittarius stream, at least out to a distance of ˜90 kpc—the largest distance to which we can reliably trace the halo using MSTO stars. We find clear evidence for a distance gradient in the Sagittarius stream across the ˜30° of sky covered by the NGVS and its flanking fields. We compare our distance measurements along the stream with those predicted by leading stream models.

  8. A Synoptic Map of Halo Substructures from the Pan-STARRS1 3π Survey

    NASA Astrophysics Data System (ADS)

    Bernard, Edouard J.; Ferguson, Annette M. N.; Schlafly, Edward F.; Martin, Nicolas F.; Rix, Hans-Walter; Bell, Eric F.; Finkbeiner, Douglas P.; Goldman, Bertrand; Martínez-Delgado, David; Sesar, Branimir; Wyse, Rosemary F. G.; Burgett, William S.; Chambers, Kenneth C.; Draper, Peter W.; Hodapp, Klaus W.; Kaiser, Nicholas; Kudritzki, Rolf-Peter; Magnier, Eugene A.; Metcalfe, Nigel; Wainscoat, Richard J.; Waters, Christopher

    2016-12-01

    We present a panoramic map of the entire Milky Way halo north of δ ˜ -30° (˜30 000 deg2), constructed by applying the matched-filter technique to the Pan-STARRS1 3π Survey data set. Using single-epoch photometry reaching to g ˜22, we are sensitive to stellar substructures with heliocentric distances between 3.5 and ˜35 kpc. We recover almost all previously reported streams in this volume and demonstrate that several of these are significantly more extended than earlier data sets have indicated. In addition, we also report five new candidate stellar streams. One of these features appears significantly broader and more luminous than the others and is likely the remnant of a dwarf galaxy. The other four streams are consistent with a globular cluster origin, and three of these are rather short in projection (≲ 10°), suggesting that streams like Ophiuchus may not be that rare. Finally, a significant number of more marginal substructures are also revealed by our analysis; many of these features can also be discerned in matched-filter maps produced by other authors from SDSS data, and hence they are very likely to be genuine. However, the extant 3π data is currently too shallow to determine their properties or produce convincing colour-magnitude diagrams. The global view of the Milky Way provided by Pan-STARRS1 provides further evidence for the important role of both globular cluster disruption and dwarf galaxy accretion in building the Milky Way's stellar halo.

  9. Tidal stripping stellar substructures around four metal-poor globular clusters in the galactic bulge

    SciTech Connect

    Chun, Sang-Hyun; Kang, Minhee; Jung, DooSeok; Sohn, Young-Jong

    2015-01-01

    We investigate the spatial density configuration of stars around four metal-poor globular clusters (NGC 6266, NGC 6626, NGC 6642, and NGC 6723) in the Galactic bulge region using wide-field deep J, H, and K imaging data obtained with the Wide Field Camera near-infrared array on the United Kingdom Infrared Telescope. A statistical weighted filtering algorithm for the stars on the color–magnitude diagram is applied in order to sort cluster member candidates from the field star contamination. In two-dimensional isodensity contour maps of the clusters, we find that all four of the globular clusters exhibit strong evidence of tidally stripped stellar features beyond the tidal radius in the form of tidal tails or small density lobes/chunks. The orientations of the extended stellar substructures are likely to be associated with the effect of dynamic interaction with the Galaxy and the cluster's space motion. The observed radial density profiles of the four globular clusters also describe the extended substructures; they depart from theoretical King and Wilson models and have an overdensity feature with a break in the slope of the profile at the outer region of clusters. The observed results could imply that four globular clusters in the Galactic bulge region have experienced strong environmental effects such as tidal forces or bulge/disk shocks of the Galaxy during the dynamical evolution of globular clusters. These observational results provide further details which add to our understanding of the evolution of clusters in the Galactic bulge region as well as the formation of the Galaxy.

  10. Two-body wear of dental porcelain and substructure oxide ceramics.

    PubMed

    Rosentritt, Martin; Preis, Verena; Behr, Michael; Hahnel, Sebastian; Handel, Gerhard; Kolbeck, Carola

    2012-06-01

    The aim of this in vitro study was to investigate the two-body wear of different ceramics. Two-body wear tests were performed in a chewing simulator with steatite and enamel antagonists, respectively. Specimens were loaded in a pin-on-block design with a vertical load of 50 N for 1.2 × 10(5) cycles; (f = 1.6 Hz; lateral movement, 1 mm; mouth opening: 2 mm). Human enamel was used as a reference. Three zirconia ceramics, three veneering porcelains, two glass-infiltrated and one lithium disilicate ceramic were investigated. Veneering and lithium disilicate ceramics were glazed before testing. Surface roughness Ra (SP6, Perthen-Feinprüf, G) and wear depth were determined using a 3D scanner (Laserscan 3D, Willytec, G). SEM (Quanta FEG 400, FEI, USA) pictures of the worn specimens and antagonists were made for evaluating wear performance. Veneering porcelain provided wear traces between 71.2 and 124.1 μm (enamel antagonist) and 117.4 and 274.1 μm (steatite). Wear of the steatite antagonists varied between 0.618 and 2.85 mm². No wear was found for zirconia and glass-infiltrated substructure ceramics. Also, no wear was found for the corresponding antagonists. Wear of specimens and antagonists was strongly material dependent. No visible wear was found on zirconia and glass-infiltrated ceramics. Porcelain and lithium disilicate ceramic showed a comparable or lower wear than the enamel reference. Antagonist wear was found to be lower when specimens were made of substructure oxide ceramics instead of veneering porcelain. From the point of wear testing, zirconia may be used for the fabrication of fixed dental prosthesis without veneering.

  11. DNA identification by pedigree likelihood ratio accommodating population substructure and mutations.

    PubMed

    Ge, Jianye; Budowle, Bruce; Chakraborty, Ranajit

    2010-10-04

    DNA typing is an important tool in missing-person identification, especially in mass-fatality disasters. Identification methods comparing a DNA profile from unidentified human remains with that of a direct (from the person) or indirect (for example, from a biological relative) reference sample and ranking the pairwise likelihood ratios (LR) is straightforward and well defined. However, for indirect comparison cases in which several members from a family can serve as reference samples, the full power of kinship analysis is not entirely exploited. Because biologically related family members are not genetically independent, more information and thus greater power can be attained by simultaneous use of all pedigree members in most cases, although distant relationships may reduce the power. In this study, an improvement was made on the method for missing-person identification for autosomal and lineage-based markers, by considering jointly the DNA profile data of all available family reference samples. The missing person is evaluated by a pedigree LR of the probability of DNA evidence under alternative hypotheses (for example, the missing person is unrelated or if they belong to this pedigree with a specified biological relationship) and can be ranked for all pedigrees within a database. Pedigree LRs are adjusted for population substructure according to the recommendations of the second National Research Council (NRCII) Report. A realistic mutation model was also incorporated to accommodate the possibility of false exclusion. The results show that the effect of mutation on the pedigree LR is moderate, but LRs can be significantly decreased by the effect of population substructure. Finally, Y chromosome and mitochondrial DNA were integrated into the analysis to increase the power of identification. A program titled MPKin was developed, combining the aforementioned features to facilitate genetic analysis for identifying missing persons. The computational complexity of the

  12. Exploring halo substructure with giant stars. XIV. The nature of the Triangulum-Andromeda stellar features

    SciTech Connect

    Sheffield, Allyson A.; Johnston, Kathryn V.; Majewski, Steven R.; Damke, Guillermo; Richardson, Whitney; Beaton, Rachael; Rocha-Pinto, Helio J. E-mail: kvj@astro.columbia.edu E-mail: gjd3r@virginia.edu E-mail: rlb9n@virginia.edu

    2014-09-20

    As large-scale stellar surveys have become available over the past decade, the ability to detect and characterize substructures in the Galaxy has increased dramatically. These surveys have revealed the Triangulum-Andromeda (TriAnd) region to be rich with substructures in the distance range 20-30 kpc, and the relation of these features to each other, if any, remains unclear. An exploration using Two Micron All Sky Survey (2MASS) photometry reveals not only the faint sequence in M giants detected by Rocha-Pinto et al. spanning the range 100° < l < 160° and –50° < b < –15°, but, in addition, a second, brighter and more densely populated sequence. These sequences are likely associated with the distinct main sequences (MSs) discovered (and labeled TriAnd1 and TriAnd2) by Martin et al. in an optical survey in the direction of M31, where TriAnd2 is the optical counterpart of the fainter red giant branch (RGB)/asymptotic giant branch sequence of Rocha-Pinto et al. Here, the age, distance, and metallicity ranges for TriAnd1 and TriAnd2 are estimated by simultaneously fitting isochrones to the 2MASS RGB tracks and the optical MS/MS turn-off features. The two populations are clearly distinct in age and distance: the brighter sequence (TriAnd1) is younger (6-10 Gyr) and closer (distance of ∼15-21 kpc), whereas the fainter sequence (TriAnd2) is older (10-12 Gyr) and at an estimated distance of ∼24-32 kpc. A comparison with simulations demonstrates that the differences and similarities between TriAnd1 and TriAnd2 can simultaneously be explained if they represent debris originating from the disruption of the same dwarf galaxy, but torn off during two distinct pericentric passages.

  13. In situ spatiotemporal measurements of the detailed azimuthal substructure of the substorm current wedge

    PubMed Central

    Forsyth, C; Fazakerley, A N; Rae, I J; J Watt, C E; Murphy, K; Wild, J A; Karlsson, T; Mutel, R; Owen, C J; Ergun, R; Masson, A; Berthomier, M; Donovan, E; Frey, H U; Matzka, J; Stolle, C; Zhang, Y

    2014-01-01

    The substorm current wedge (SCW) is a fundamental component of geomagnetic substorms. Models tend to describe the SCW as a simple line current flowing into the ionosphere toward dawn and out of the ionosphere toward dusk, linked by a westward electrojet. We use multispacecraft observations from perigee passes of the Cluster 1 and 4 spacecraft during a substorm on 15 January 2010, in conjunction with ground-based observations, to examine the spatial structuring and temporal variability of the SCW. At this time, the spacecraft traveled east-west azimuthally above the auroral region. We show that the SCW has significant azimuthal substructure on scales of 100 km at altitudes of 4000–7000 km. We identify 26 individual current sheets in the Cluster 4 data and 34 individual current sheets in the Cluster 1 data, with Cluster 1 passing through the SCW 120–240 s after Cluster 4 at 1300–2000 km higher altitude. Both spacecraft observed large-scale regions of net upward and downward field-aligned current, consistent with the large-scale characteristics of the SCW, although sheets of oppositely directed currents were observed within both regions. We show that the majority of these current sheets were closely aligned to a north-south direction, in contrast to the expected east-west orientation of the preonset aurora. Comparing our results with observations of the field-aligned current associated with bursty bulk flows (BBFs), we conclude that significant questions remain for the explanation of SCW structuring by BBF-driven “wedgelets.” Our results therefore represent constraints on future modeling and theoretical frameworks on the generation of the SCW. Key Points The substorm current wedge (SCW) has significant azimuthal structure Current sheets within the SCW are north-south aligned The substructure of the SCW raises questions for the proposed wedgelet scenario PMID:26167439

  14. DEFORMATION SUBSTRUCTURES AND THEIR TRANSITIONS IN LASER SHOCK-COMPRESSED COPPER-ALUMINUM ALLOYS

    SciTech Connect

    Meyers, M A; Schneider, M S; Jarmakani, H; Kad, B; Remington, B A; Kalantar, D H; McNaney, J; Cao, B; Wark, J

    2007-10-17

    It is shown that the short pulse durations (0.1-10 ns) in laser shock compression ensure a rapid decay of the pulse and quenching of the shocked sample in times that are orders of magnitude lower than in conventional explosively driven plate impact experiments. Thus, laser compression, by virtue of a much more rapid cooling, enables the retention of a deformation structure closer to the one existing during shock. The smaller pulse length also decreases the propensity for localization. Copper and copper aluminum (2 and 6 wt% Al) with orientations [001] and [{bar 1}34] were subjected to high intensity laser pulses with energy levels of 70 to 300 J delivered in an initial pulse duration of approximately 3 ns. The [001] and [{bar 1}34] orientations were chosen since they respectively maximize and minimize the number of slip systems with highest resolved shear stresses. Systematic differences of the defect substructure were observed as a function of pressure, stacking-fault energy and crystalline orientation. The changes in the mechanical properties for each condition were compared using micro- and nano-hardness measurements and correlated well with observations of the defect substructure. Three regimes of plastic deformation were identified and their transitions modeled: dislocation cells, stacking-faults, and twins. An existing constitutive description of the slip to twinning transition, based on the critical shear stress, was expanded to incorporate the effect of stacking-fault energy. A new physically-based criterion accounting for stacking-fault energy was developed that describes the transition from perfect loop to partial loop homogeneous nucleation, and consequently from cells to stacking-faults. These calculations predict transitions that are in qualitative agreement with the effect of SFE.

  15. Structure and substructure analysis of DAFT/FADA galaxy clusters in the [0.4-0.9] redshift range

    NASA Astrophysics Data System (ADS)

    Guennou, L.; Adami, C.; Durret, F.; Lima Neto, G. B.; Ulmer, M. P.; Clowe, D.; LeBrun, V.; Martinet, N.; Allam, S.; Annis, J.; Basa, S.; Benoist, C.; Biviano, A.; Cappi, A.; Cypriano, E. S.; Gavazzi, R.; Halliday, C.; Ilbert, O.; Jullo, E.; Just, D.; Limousin, M.; Márquez, I.; Mazure, A.; Murphy, K. J.; Plana, H.; Rostagni, F.; Russeil, D.; Schirmer, M.; Slezak, E.; Tucker, D.; Zaritsky, D.; Ziegler, B.

    2014-01-01

    Context. The DAFT/FADA survey is based on the study of ~90 rich (masses found in the literature >2 × 1014 M⊙) and moderately distant clusters (redshifts 0.4 < z < 0.9), all with HST imaging data available. This survey has two main objectives: to constrain dark energy (DE) using weak lensing tomography on galaxy clusters and to build a database (deep multi-band imaging allowing photometric redshift estimates, spectroscopic data, X-ray data) of rich distant clusters to study their properties. Aims: We analyse the structures of all the clusters in the DAFT/FADA survey for which XMM-Newton and/or a sufficient number of galaxy redshifts in the cluster range are available, with the aim of detecting substructures and evidence for merging events. These properties are discussed in the framework of standard cold dark matter (ΛCDM) cosmology. Methods: In X-rays, we analysed the XMM-Newton data available, fit a β-model, and subtracted it to identify residuals. We used Chandra data, when available, to identify point sources. In the optical, we applied a Serna & Gerbal (SG) analysis to clusters with at least 15 spectroscopic galaxy redshifts available in the cluster range. We discuss the substructure detection efficiencies of both methods. Results: XMM-Newton data were available for 32 clusters, for which we derive the X-ray luminosity and a global X-ray temperature for 25 of them. For 23 clusters we were able to fit the X-ray emissivity with a β-model and subtract it to detect substructures in the X-ray gas. A dynamical analysis based on the SG method was applied to the clusters having at least 15 spectroscopic galaxy redshifts in the cluster range: 18 X-ray clusters and 11 clusters with no X-ray data. The choice of a minimum number of 15 redshifts implies that only major substructures will be detected. Ten substructures were detected both in X-rays and by the SG method. Most of the substructures detected both in X-rays and with the SG method are probably at their first

  16. Binding of the winged-helix transcription factor HNF3 to a linker histone site on the nucleosome.

    PubMed Central

    Cirillo, L A; McPherson, C E; Bossard, P; Stevens, K; Cherian, S; Shim, E Y; Clark, K L; Burley, S K; Zaret, K S

    1998-01-01

    The transcription factor HNF3 and linker histones H1 and H5 possess winged-helix DNA-binding domains, yet HNF3 and other fork head-related proteins activate genes during development whereas linker histones compact DNA in chromatin and repress gene expression. We compared how the two classes of factors interact with chromatin templates and found that HNF3 binds DNA at the side of nucleosome cores, similarly to what has been reported for linker histone. A nucleosome structural binding site for HNF3 is occupied at the albumin transcriptional enhancer in active and potentially active chromatin, but not in inactive chromatin in vivo. While wild-type HNF3 protein does not compact DNA extending from the nucleosome, as does linker histone, site-directed mutants of HNF3 can compact nucleosomal DNA if they contain basic amino acids at positions previously shown to be essential for nucleosomal DNA compaction by linker histones. The results illustrate how transcription factors can possess special nucleosome-binding activities that are not predicted from studies of factor interactions with free DNA. PMID:9427758

  17. Effect of linker length between variable domains of single chain variable fragment antibody against daidzin on its reactivity.

    PubMed

    Yusakul, Gorawit; Sakamoto, Seiichi; Pongkitwitoon, Benyakan; Tanaka, Hiroyuki; Morimoto, Satoshi

    2016-07-01

    The peptide linker between variable domains of heavy (VH) and light (VL) chains is one of important factors that influence the characteristics of scFv, including binding activity and specificity against target antigen. The scFvs against daidzin (DZ-scFvs) with different linker lengths were constructed in the format of VH-(GGGGS)n-VL (n = 1, 3, 5, and 7). They were expressed in the hemolymph of silkworm larvae using the Bombyx mori nucleopolyhedrovirus (BmNPV) bacmid DNA system, and their reactivity against daidzin and related compounds were evaluated using an indirect competitive enzyme-linked immunosorbent assay (icELISA), which is applicable for quantitative analysis of daidzin. The results showed that the reactivity of scFvs against daidzin was increased, whereas specificity slightly decreased when their peptide linker was lengthened. These results suggested that the linker length of DZ-scFvs contributes to its reactivity. In addition, the results emphasize that the linker length could control the reactivity of DZ-scFvs.

  18. Synthesis, characterization, monolayer assembly and 2D lanthanide coordination of a linear terphenyl-di(propiolonitrile) linker on Ag(111).

    PubMed

    Chen, Zhi; Klyatskaya, Svetlana; Urgel, José I; Écija, David; Fuhr, Olaf; Auwärter, Willi; Barth, Johannes V; Ruben, Mario

    2015-01-01

    As a continuation of our work employing polyphenylene-dicarbonitrile molecules and in particular the terphenyl derivative 1 (TDCN), we have synthesized a novel ditopic terphenyl-4,4"-di(propiolonitrile) (2) linker for the self-assembly of organic monolayers and metal coordination at interfaces. The structure of the organic linker 2 was confirmed by single crystal X-ray diffraction analysis (XRD). On the densely packed Ag(111) surface, the terphenyl-4,4"-di(propiolonitrile) linkers self-assemble in a regular, molecular chevron arrangement exhibiting a Moiré pattern. After the exposure of the molecular monolayer to a beam of Gd atoms, the propiolonitrile groups get readily involved in metal-ligand coordination interactions. Distinct coordination motifs evolve with coordination numbers varying between three and six for the laterally-bound Gd centers. The linker molecules retain an overall flat adsorption geometry. However, only networks with restricted local order were obtained, in marked contrast to previously employed, simpler polyphenylene-dicarbonitrile 1 linkers.

  19. Constitutive Smad linker phosphorylation in melanoma: a mechanism of resistance to transforming growth factor-β-mediated growth inhibition.

    PubMed

    Cohen-Solal, Karine A; Merrigan, Kim T; Chan, Joseph L-K; Goydos, James S; Chen, Wenjin; Foran, David J; Liu, Fang; Lasfar, Ahmed; Reiss, Michael

    2011-06-01

    Melanoma cells are resistant to transforming growth factor-β (TGFβ)-induced cell-cycle arrest. In this study, we investigated a mechanism of resistance involving a regulatory domain, called linker region, in Smad2 and Smad3, main downstream effectors of TGFβ. Melanoma cells in culture and tumor samples exhibited constitutive Smad2 and Smad3 linker phosphorylation. Treatment of melanoma cells with the MEK1/2 inhibitor, U0126, or the two pan-CDK and GSK3 inhibitors, Flavopiridol and R547, resulted in decreased linker phosphorylation of Smad2 and Smad3. Overexpression of the linker phosphorylation-resistant Smad3 EPSM mutant in melanoma cells resulted in an increase in expression of p15(INK4B) and p21(WAF1) , as compared with cells transfected with wild-type (WT) Smad3. In addition, the cell numbers of EPSM Smad3-expressing melanoma cells were significantly reduced compared with WT Smad3-expressing cells. These results suggest that the linker phosphorylation of Smad3 contributes to the resistance of melanoma cells to TGFβ-mediated growth inhibition.

  20. Adenoviral vector tethering to metal surfaces via hydrolyzable cross-linkers for the modulation of vector release and transduction.

    PubMed

    Fishbein, Ilia; Forbes, Scott P; Chorny, Michael; Connolly, Jeanne M; Adamo, Richard F; Corrales, Ricardo A; Alferiev, Ivan S; Levy, Robert J

    2013-09-01

    The use of arterial stents and other medical implants as a delivery platform for surface immobilized gene vectors allows for safe and efficient localized expression of therapeutic transgenes. In this study we investigate the use of hydrolyzable cross-linkers with distinct kinetics of hydrolysis for delivery of gene vectors from polyallylamine bisphosphonate-modified metal surfaces. Three cross-linkers with the estimated t1/2 of ester bonds hydrolysis of 5, 12 and 50 days demonstrated a cumulative 20%, 39% and 45% vector release, respectively, after 30 days exposure to physiological buffer at 37 °C. Transgene expression in endothelial and smooth muscles cells transduced with substrate immobilized adenovirus resulted in significantly different expression profiles for each individual cross-linker. Furthermore, immobilization of adenoviral vectors effectively extended their transduction effectiveness beyond the initial phase of release. Transgene expression driven by adenovirus-tethered stents in rat carotid arteries demonstrated that a faster rate of cross-linker hydrolysis resulted in higher expression levels at day 1, which declined by day 8 after stent implantation, while inversely, slower hydrolysis was associated with increased arterial expression at day 8 in comparison with day 1. In conclusion, adjustable release of transduction-competent adenoviral vectors from metallic surfaces can be achieved, both in vitro and in vivo, through surface immobilization of adenoviral vectors using hydrolyzable cross-linkers with structure-specific release kinetics.

  1. Stability analysis and comparative experimentation for two substructuring schemes, with a pure time delay in the actuation system

    NASA Astrophysics Data System (ADS)

    Enokida, Ryuta; Stoten, David; Kajiwara, Koichi

    2015-06-01

    In recent years there has been a focus on two types of scheme for dynamical substructure testing: the hybrid scheme (HS) and the dynamically substructured system (DSS) scheme. Although these approaches are fundamentally different in the manner of compensation/control, the comparative performance of the schemes has not yet been studied in simulated or real experimental tests. This paper studies the performance of these schemes via tests on a simple base-isolated structure with a natural rubber bearing. In dynamical tests, a guarantee of stability for the experimental system is essential in order to achieve a safe and reliable result. Pure time delays can be present in such experimental systems, primarily due to discrete-time computational elements, which will promote instability. This paper studies the stability of HS and DSS test systems, with a prime focus on the effect of pure time delays. In particular the schemes were applied to the substructure testing of a rubber isolation bearing, where the overall system included a digital computation time delay of τ=6 ms resulting from a series of control, data acquisition and signal filter elements. Neither delay compensation nor adaptive/self-tuning methods were included in these tests, in order to establish a fair and objective comparison between the basic forms of the two schemes. It was found that DSS stability was preserved in the presence of the 6 ms delay, whereas HS was rendered unstable. This increase in robustness was due to a linear substructure controller (LSC) used in the DSS, which was based upon a knowledge of the dynamics of the transfer system and substructures. In addition, DSS exhibited significant robustness to further artificial increases in the pure time delay, eventually yielding to instability at a value of τ=17 ms. Analysis of the two schemes was found to be effective at predicting accurate stability conditions in advance of actual experimentation.

  2. A minimal phycobilisome: fusion and chromophorylation of the truncated core-membrane linker and phycocyanin.

    PubMed

    Tang, Kun; Zeng, Xiao-Li; Yang, Yi; Wang, Zhi-Bin; Wu, Xian-Jun; Zhou, Ming; Noy, Dror; Scheer, Hugo; Zhao, Kai-Hong

    2012-07-01

    Phycobilisomes, the light-harvesting antennas in cyanobacteria and red algae, consist of an allophycocyanin core that is attached to the membrane via a core-membrane linker, and rods comprised of phycocyanin and often also phycoerythrin or phycoerythrocyanin. Phycobiliproteins show excellent energy transfer among the chromophores that renders them biomarkers with large Stokes-shifts absorbing over most of the visible spectrum and into the near infrared. Their application is limited, however, due to covalent binding of the chromophores and by solubility problems. We report construction of a water-soluble minimal chromophore-binding unit of the red-absorbing and fluorescing core-membrane linker. This was fused to minimal chromophore-binding units of phycocyanin. After double chromophorylation with phycocyanobilin, in E. coli, the fused phycobiliproteins absorbed light in the range of 610-660nm, and fluoresced at ~670nm, similar to phycobilisomes devoid of phycoerythr(ocyan)in. The fused phycobiliprotein could also be doubly chromophorylated with phycoerythrobilin, resulting in a chromoprotein absorbing around 540-575nm, and fluorescing at ~585nm. The broad absorptions and the large Stokes shifts render these chromoproteins candidates for imaging; they may also be helpful in studying phycobilisome assembly.

  3. Peroxisomes move by hitchhiking on early endosomes using the novel linker protein PxdA

    PubMed Central

    Salogiannis, John; Egan, Martin J.

    2016-01-01

    Eukaryotic cells use microtubule-based intracellular transport for the delivery of many subcellular cargos, including organelles. The canonical view of organelle transport is that organelles directly recruit molecular motors via cargo-specific adaptors. In contrast with this view, we show here that peroxisomes move by hitchhiking on early endosomes, an organelle that directly recruits the transport machinery. Using the filamentous fungus Aspergillus nidulans we found that hitchhiking is mediated by a novel endosome-associated linker protein, PxdA. PxdA is required for normal distribution and long-range movement of peroxisomes, but not early endosomes or nuclei. Using simultaneous time-lapse imaging, we find that early endosome-associated PxdA localizes to the leading edge of moving peroxisomes. We identify a coiled-coil region within PxdA that is necessary and sufficient for early endosome localization and peroxisome distribution and motility. These results present a new mechanism of microtubule-based organelle transport in which peroxisomes hitchhike on early endosomes and identify PxdA as the novel linker protein required for this coupling. PMID:26811422

  4. Nucleosome linker proteins HMGB1 and histone H1 differentially enhance DNA ligation reactions.

    PubMed

    Yamanaka, Shiho; Katayama, Eisaku; Yoshioka, Ken-ichi; Nagaki, Sumiko; Yoshida, Michiteru; Teraoka, Hirobumi

    2002-03-22

    We previously reported that HMGB1, which originally binds to chromatin in a manner competitive with linker histone H1 to modulate chromatin structure, enhances both intra-molecular and inter-molecular ligations. In this paper, we found that histone H1 differentially enhances ligation reaction of DNA double-strand breaks (DSB). Histone H1 stimulated exclusively inter-molecular ligation reaction of DSB with DNA ligase IIIbeta and IV, whereas HMGB1 enhanced mainly intra-molecular ligation reaction. Electron microscopy of direct DNA-protein interaction without chemical cross-linking visualized that HMGB1 bends and loops linear DNA to form compact DNA structure and that histone H1 is capable of assembling DNA in tandem arrangement with occasional branches. These results suggest that differences in the enhancement of DNA ligation reaction are due to those in alteration of DNA configuration induced by these two linker proteins. HMGB1 and histone H1 may function in non-homologous end-joining of DSB repair and V(D)J recombination in different manners.

  5. Deimination of linker histones links neutrophil extracellular trap release with autoantibodies in systemic autoimmunity.

    PubMed

    Dwivedi, Nishant; Neeli, Indira; Schall, Nicolas; Wan, Haibao; Desiderio, Dominic M; Csernok, Elena; Thompson, Paul R; Dali, Hayet; Briand, Jean-Paul; Muller, Sylviane; Radic, Marko

    2014-07-01

    Autoantibodies to nuclear antigens arise in human autoimmune diseases, but a unifying pathogenetic mechanism remains elusive. Recently we reported that exposure of neutrophils to inflammatory conditions induces the citrullination of core histones by peptidylarginine deiminase 4 (PAD4) and that patients with autoimmune disorders produce autoantibodies that recognize such citrullinated histones. Here we identify histone H1 as an additional substrate of PAD4, localize H1 within neutrophil extracellular traps, and detect autoantibodies to citrullinated H1 in 6% of sera from patients with systemic lupus erythematosus and Sjögren's syndrome. No preference for deiminated H1 was observed in healthy control sera and sera from patients with scleroderma or rheumatoid arthritis. We map binding to the winged helix of H1 and determine that citrulline 53 represents a key determinant of the autoantibody epitope. In addition, we quantitate RNA for H1 histone subtypes in mature human neutrophils and identify citrulline residues by liquid chromatography and tandem mass spectrometry. Our results indicate that deimination of linker histones generates new autoantibody epitopes with enhanced potential for stimulating autoreactive human B cells.-Dwivedi, N., Neeli, I., Schall, N., Wan, H., Desiderio, D. M., Csernok, E., Thompson, P. R., Dali, H., Briand, J.-P., Muller, S., Radic, M. Deimination of linker histones links neutrophil extracellular trap release with autoantibodies in systemic autoimmunity.

  6. Trifunctional cross-linker for mapping protein-protein interaction networks and comparing protein conformational states

    PubMed Central

    Tan, Dan; Li, Qiang; Zhang, Mei-Jun; Liu, Chao; Ma, Chengying; Zhang, Pan; Ding, Yue-He; Fan, Sheng-Bo; Tao, Li; Yang, Bing; Li, Xiangke; Ma, Shoucai; Liu, Junjie; Feng, Boya; Liu, Xiaohui; Wang, Hong-Wei; He, Si-Min; Gao, Ning; Ye, Keqiong; Dong, Meng-Qiu; Lei, Xiaoguang

    2016-01-01

    To improve chemical cross-linking of proteins coupled with mass spectrometry (CXMS), we developed a lysine-targeted enrichable cross-linker containing a biotin tag for affinity purification, a chemical cleavage site to separate cross-linked peptides away from biotin after enrichment, and a spacer arm that can be labeled with stable isotopes for quantitation. By locating the flexible proteins on the surface of 70S ribosome, we show that this trifunctional cross-linker is effective at attaining structural information not easily attainable by crystallography and electron microscopy. From a crude Rrp46 immunoprecipitate, it helped identify two direct binding partners of Rrp46 and 15 protein-protein interactions (PPIs) among the co-immunoprecipitated exosome subunits. Applying it to E. coli and C. elegans lysates, we identified 3130 and 893 inter-linked lysine pairs, representing 677 and 121 PPIs. Using a quantitative CXMS workflow we demonstrate that it can reveal changes in the reactivity of lysine residues due to protein-nucleic acid interaction. DOI: http://dx.doi.org/10.7554/eLife.12509.001 PMID:26952210

  7. Multivalent linkers for improved covalent binding of oligonucleotides to dye-doped silica nanoparticles

    NASA Astrophysics Data System (ADS)

    Kelleher, S. M.; Nooney, R. I.; Flynn, S. P.; Clancy, E.; Burke, M.; Daly, S.; Smith, T. J.; Daniels, S.; McDonagh, C.

    2015-09-01

    This paper describes the fabrication of oligonucleotide-coated Cy5-doped silica nanoparticles using a combination of multivalent linkers and their use in surface-based DNA sandwich hybridization assays. Dipodal silane is introduced as a means to fabricate amine-coated silica nanoparticles and its advantages compared to monopodal silanes are discussed. The use of dipodal silane in conjunction with three different polymer linkers (oxidized dextran, linear and 8-arm polyethylene glycol (PEG)) to immobilize single-stranded DNA to Cy5-doped nanoparticles is investigated and dynamic light scattering measurements and Fourier transform infrared spectroscopy are used to follow the progression of the functionalization of the nanoparticles. We observe a significant improvement in the binding stability of the single-stranded DNA when the dipodal silane and 8-arm PEG are used in combination, when compared to alternative conjugation strategies. Both 8mer and 22mer oligonucleotides are securely conjugated to the high-brightness nanoparticles and their availability to hybridize with a complementary strand is confirmed using solution-based DNA hybridization experiments. In addition, a full surface-based sandwich assay demonstrates the potential these nanoparticles have in the detection of less than 500 femtomolar of a DNA analogue of micro RNA, miR-451.

  8. Effective generation of transgenic pigs and mice by linker based sperm-mediated gene transfer.

    PubMed Central

    2002-01-01

    Background Transgenic animals have become valuable tools for both research and applied purposes. The current method of gene transfer, microinjection, which is widely used in transgenic mouse production, has only had limited success in producing transgenic animals of larger or higher species. Here, we report a linker based sperm-mediated gene transfer method (LB-SMGT) that greatly improves the production efficiency of large transgenic animals. Results The linker protein, a monoclonal antibody (mAb C), is reactive to a surface antigen on sperm of all tested species including pig, mouse, chicken, cow, goat, sheep, and human. mAb C is a basic protein that binds to DNA through ionic interaction allowing exogenous DNA to be linked specifically to sperm. After fertilization of the egg, the DNA is shown to be successfully integrated into the genome of viable pig and mouse offspring with germ-line transfer to the F1 generation at a highly efficient rate: 37.5% of pigs and 33% of mice. The integration is demonstrated again by FISH analysis and F2 transmission in pigs. Furthermore, expression of the transgene is demonstrated in 61% (35/57) of transgenic pigs (F0 generation). Conclusions Our data suggests that LB-SMGT could be used to generate transgenic animals efficiently in many different species. PMID:11964188

  9. SKI promotes Smad3 linker phosphorylations associated with the tumor-promoting trait of TGFbeta.

    PubMed

    Lin, Qiushi; Chen, Dahu; Timchenko, Nikolai A; Medrano, Estela E

    2010-05-01

    The transcriptional co-regulator SKI is a potent inhibitor of TGFbeta-growth inhibitory signals. SKI binds to receptor-activated Smads in the nucleus, forming repressor complexes containing HDACs, mSin3, NCoR, and other protein partners. Alternatively, SKI binds to activated Smads in the cytoplasm, preventing their nuclear translocation. SKI is necessary for anchorage-independent growth of melanoma cells in vitro, and most important, for human melanoma xenograft growth in vivo. We recently identified a novel role of SKI in TGFbeta signaling. SKI promotes the switch of Smad3 from repressor of proliferation to activator of oncogenesis by facilitating phosphorylations in the linker domain. High levels of endogenous SKI are required by the tumor promoting trait of TGFbeta to induce expression of the plasminogen-activator inhibitor-1 (PAI-1), sustained expression of C-Myc and for aborting upregulation of p21(Waf-1). Here we discuss how SKI diversifies and amplifies its functions by associating with multiple protein partners and by promoting Smad3 linker phosphorylation(s) in response to TGFbeta signaling in melanoma cells.

  10. Linker-Induced Anomalous Emission of Organic-Molecule Conjugated Metal-Oxide Nanoparticles

    SciTech Connect

    Turkowski, Volodymyr; Babu, Suresh; Le, Duy; Kumar, Amit; Haldar, Manas K.; Wagh, Anil V.; Hu, Zhongjian; Karakoti, Ajay S.; Gesquiere, Andre J.; Law, Benedict; Mallik, Sanku; Rahman, Talat S.; Leuenberger, Michael N.; Seal, Sudipta

    2012-06-26

    Semiconductor nanoparticles conjugated with organic- and dye-molecules to yield high efficiency visible photoluminescence (PL) hold great potential for many future technological applications. We show that folic acid (FA)-conjugated to nanosize TiO2 and CeO2 particles demonstrates a dramatic increase of photoemission intensity at wavelengths between 500 and 700 nm when derivatized using aminopropyl trimethoxysilane (APTMS) as spacer-linker molecules between the metal oxide and FA. Using density-functional theory (DFT) and time-dependent DFT calculations we demonstrate that the strong increase of the PL can be explained by electronic transitions between the titania surface oxygen vacancy (OV) states and the low-energy excited states of the FA/APTMS molecule anchored onto the surface oxygen bridge sites in close proximity to the OVs. We suggest this scenario to be a universal feature for a wide class of metal oxide nanoparticles, including nanoceria, possessing a similar band gap (3 eV) and with a large surface-vacancy-related density of electronic states. We demonstrate that the molecule-nanoparticle linker can play a crucial role in tuning the electronic and optical properties of nanosystems by bringing optically active parts of the molecule and of the surface close to each other.

  11. A simple LC/MRM-MS-based method to quantify free linker-payload in antibody-drug conjugate preparations.

    PubMed

    Zmolek, Wesley; Bañas, Stefanie; Barfield, Robyn M; Rabuka, David; Drake, Penelope M

    2016-10-01

    Antibody-drug conjugates represent a growing class of biologic drugs that use the targeted specificity of an antibody to direct the localization of a small molecule drug, often a cytotoxic payload. After conjugation, antibody-drug conjugate preparations typically retain a residual amount of free (unconjugated) linker-payload. Monitoring this free small molecule drug component is important due to the potential for free payload to mediate unintended (off-target) toxicity. We developed a simple RP-HPLC/MRM-MS-based assay that can be rapidly employed to quantify free linker-payload. The method uses low sample volumes and offers an LLOQ of 10nM with 370pg on column. This analytical approach was used to monitor free linker-payload removal during optimization of the tangential flow filtration manufacturing step.

  12. Piezoelectric crystal impedance analysis for investigating the modification processes of protein, cross-linker, and DNA on gold surface

    NASA Astrophysics Data System (ADS)

    Zhou, Anhong; Xie, Qingji; Li, Ping; Nie, Lihua; Yao, Shouzhuo

    2000-05-01

    The processes of surface modification on gold-coated piezoelectric quartz crystal sensor have been in situ investigated by using the impedance analysis technique. The changes of equivalent circuit parameters were used to interpret the different behaviors of successively modifying protein, cross-linker, and DNA onto a gold electrode surface. It was found that the frequency changes due to protein adsorption might be described as a sum of two exponential functions, compared with a first-order kinetic function exhibited in subsequent binding of cross-linker to protein. The kinetic parameters were fitted to these two cases. It was also shown that the DNA molecules binding to cross-linker gave rise to the changes of the density-viscosity and the dielectric constant, both being linearly related to DNA concentration in the liquid when below 6.0 μg m -1.

  13. Rigidifying Fluorescent Linkers by Metal-Organic Framework Formation for Fluorescence Blue Shift and Quantum Yield Enhancement

    SciTech Connect

    Wei, ZW; Gu, ZY; Arvapally, RK; Chen, YP; McDougald, RN; Ivy, JF; Yakovenko, AA; Feng, DW; Omary, MA; Zhou, HC

    2014-06-11

    We demonstrate that rigidifying the structure of fluorescent linkers by structurally constraining them in metal-organic frameworks (MOFs) to control their conformation effectively tunes the fluorescence energy and enhances the quantum yield. Thus, a new tetraphenylethylene-based zirconium MOF exhibits a deep-blue fluorescent emission at 470 nm with a unity quantum yield (99.9 +/- 0.5%) under Ar, representing ca. 3600 cm(-1) blue shift and doubled radiative decay efficiency vs the linker precursor. An anomalous increase in the fluorescence lifetime and relative intensity takes place upon heating the solid MOF from cryogenic to ambient temperatures. The origin of these unusual photoluminescence properties is attributed to twisted linker conformation, intramolecular hindrance, and framework rigidity.

  14. Rigidifying Fluorescent Linkers by Metal–Organic Framework Formation for Fluorescence Blue Shift and Quantum Yield Enhancement

    SciTech Connect

    Wei, Zhangwen; Gu, Zhi-Yuan; Arvapally, Ravi K.; Chen, Ying-Pin; Ivy, Joshua F.; Yakovenko, Andrey A.; Feng, Dawei; Omary, Mohammad A.; Zhou, Hong-Cai

    2014-06-11

    We demonstrate that rigidifying the structure of fluorescent linkers by structurally constraining them in metal–organic frameworks (MOFs) to control their conformation effectively tunes the fluorescence energy and enhances the quantum yield. Thus, a new tetraphenylethylene-based zirconium MOF exhibits a deep-blue fluorescent emission at 470 nm with a unity quantum yield (99.9 ± 0.5%) under Ar, representing ca. 3600 cm⁻¹ blue shift and doubled radiative decay efficiency vs the linker precursor. An anomalous increase in the fluorescence lifetime and relative intensity takes place upon heating the solid MOF from cryogenic to ambient temperatures. The origin of these unusual photoluminescence properties is attributed to twisted linker conformation, intramolecular hindrance, and framework rigidity.

  15. Influence of Cross-Linkers on the in Vitro Chondrogenesis of Mesenchymal Stem Cells in Hyaluronic Acid Hydrogels.

    PubMed

    Maturavongsadit, Panita; Bi, Xiangdong; Metavarayuth, Kamolrat; Luckanagul, Jittima Amie; Wang, Qian

    2017-02-01

    This study aims to investigate the effect of the structures of cross-linkers on the in vitro chondrogenic differentiation of bone mesenchymal stem cells (BMSCs) in hyaluronic acid (HA)-based hydrogels. The hydrogels were prepared by the covalent cross-linking of methacrylated HA with different types of thiol-tailored molecules, including dithiothreitol (DTT), 4-arm poly(ethylene glycol) (PEG), and multiarm polyamidoamine (PAMAM) dendrimer using thiol-ene "click" chemistry. The microstructure, mechanical properties, diffusivity, and degradation rates of the resultant hydrogels were controlled by the structural feature of different cross-linkers. BMSCs were then encapsulated in the resulting hydrogels and cultured in chondrogenic conditions. Overall, chondrogenic differentiation was highly enhanced in the PEG-cross-linked HA hydrogels, as measured by glycosaminoglycan (GAG) and collagen accumulation. The physical properties of hydrogels, especially the mechanical property and microarchitecture, were resulted from the structures of different cross-linkers, which subsequently modulated the fate of BMSC differentiation.

  16. High-resolution Y chromosome haplotypes of Israeli and Palestinian Arabs reveal geographic substructure and substantial overlap with haplotypes of Jews.

    PubMed

    Nebel, A; Filon, D; Weiss, D A; Weale, M; Faerman, M; Oppenheim, A; Thomas, M G

    2000-12-01

    High-resolution Y chromosome haplotype analysis was performed in 143 paternally unrelated Israeli and Palestinian Moslem Arabs (I&P Arabs) by screening for 11 binary polymorphisms and six microsatellite loci. Two frequent haplotypes were found among the 83 detected: the modal haplotype of the I&P Arabs (approximately 14%) was spread throughout the region, while its one-step microsatellite neighbor, the modal haplotype of the Galilee sample (approximately 8%), was mainly restricted to the north. Geographic substructuring within the Arabs was observed in the highlands of Samaria and Judea. Y chromosome variation in the I&P Arabs was compared to that of Ashkenazi and Sephardic Jews, and to that of North Welsh individuals. At the haplogroup level, defined by the binary polymorphisms only, the Y chromosome distribution in Arabs and Jews was similar but not identical. At the haplotype level, determined by both binary and microsatellite markers, a more detailed pattern was observed. Single-step microsatellite networks of Arab and Jewish haplotypes revealed a common pool for a large portion of Y chromosomes, suggesting a relatively recent common ancestry. The two modal haplotypes in the I&P Arabs were closely related to the most frequent haplotype of Jews (the Cohen modal haplotype). However, the I&P Arab clade that includes the two Arab modal haplotypes (and makes up 32% of Arab chromosomes) is found at only very low frequency among Jews, reflecting divergence and/or admixture from other populations.

  17. Silyl-based alkyne-modifying linker for the preparation of C-terminal acetylene-derivatized protected peptides.

    PubMed

    Strack, Martin; Langklotz, Sina; Bandow, Julia E; Metzler-Nolte, Nils; Albada, H Bauke

    2012-11-16

    A novel linker for the synthesis of C-terminal acetylene-functionalized protected peptides is described. This SAM1 linker is applied in the manual Fmoc-based solid-phase peptide synthesis of Leu-enkephalin and in microwave-assisted automated synthesis of Maculatin 2.1, an antibacterial peptide that contains 18 amino acid residues. For the cleavage, treatment with tetramethylammonium fluoride results in protected acetylene-derivatized peptides. Alternatively, a one-pot cleavage-click procedure affords the protected 1,2,3-triazole conjugate in high yields after purification.

  18. Mixed-linker approach in designing porous zirconium-based metal-organic frameworks with high hydrogen storage capacity.

    PubMed

    Naeem, Ayesha; Ting, Valeska P; Hintermair, Ulrich; Tian, Mi; Telford, Richard; Halim, Saaiba; Nowell, Harriott; Hołyńska, Małgorzata; Teat, Simon J; Scowen, Ian J; Nayak, Sanjit

    2016-06-14

    Three highly porous Zr(iv)-based metal-organic frameworks, UBMOF-8, UBMOF-9, and UBMOF-31, were synthesized by using 2,2'-diamino-4,4'-stilbenedicarboxylic acid, 4,4'-stilbenedicarboxylic acid, and combination of both linkers, respectively. The mixed-linker UBMOF-31 showed excellent hydrogen uptake of 4.9 wt% and high selectivity for adsorption of CO2 over N2 with high thermal stability and moderate water stability with permanent porosity and surface area of 2552 m(2) g(-1).

  19. Developing an Acidic Residue Reactive and Sulfoxide-Containing MS-Cleavable Homobifunctional Cross-Linker for Probing Protein–Protein Interactions

    PubMed Central

    2016-01-01

    Cross-linking mass spectrometry (XL-MS) has become a powerful strategy for defining protein–protein interactions and elucidating architectures of large protein complexes. However, one of the inherent challenges in MS analysis of cross-linked peptides is their unambiguous identification. To facilitate this process, we have previously developed a series of amine-reactive sulfoxide-containing MS-cleavable cross-linkers. These MS-cleavable reagents have allowed us to establish a common robust XL-MS workflow that enables fast and accurate identification of cross-linked peptides using multistage tandem mass spectrometry (MSn). Although amine-reactive reagents targeting lysine residues have been successful, it remains difficult to characterize protein interaction interfaces with little or no lysine residues. To expand the coverage of protein interaction regions, we present here the development of a new acidic residue-targeting sulfoxide-containing MS-cleavable homobifunctional cross-linker, dihydrazide sulfoxide (DHSO). We demonstrate that DHSO cross-linked peptides display the same predictable and characteristic fragmentation pattern during collision induced dissociation as amine-reactive sulfoxide-containing MS-cleavable cross-linked peptides, thus permitting their simplified analysis and unambiguous identification by MSn. Additionally, we show that DHSO can provide complementary data to amine-reactive reagents. Collectively, this work not only enlarges the range of the application of XL-MS approaches but also further demonstrates the robustness and applicability of sulfoxide-based MS-cleavability in conjunction with various cross-linking chemistries. PMID:27417384

  20. Preferential interaction of the core histone tail domains with linker DNA.

    PubMed

    Angelov, D; Vitolo, J M; Mutskov, V; Dimitrov, S; Hayes, J J

    2001-06-05

    Within chromatin, the core histone tail domains play critical roles in regulating the structure and accessibility of nucleosomal DNA within the chromatin fiber. Thus, many nuclear processes are facilitated by concomitant posttranslational modification of these domains. However, elucidation of the mechanisms by which the tails mediate such processes awaits definition of tail interactions within chromatin. In this study we have investigated the primary DNA target of the majority of the tails in mononucleosomes. The results clearly show that the tails bind preferentially to "linker" DNA, outside of the DNA encompassed by the nucleosome core. These results have important implications for models of tail function within the chromatin fiber and for in vitro structural and functional studies using nucleosome core particles.

  1. Selective histone deacetylase 6 inhibitors bearing substituted urea linkers inhibit melanoma cell growth.

    PubMed

    Bergman, Joel A; Woan, Karrune; Perez-Villarroel, Patricio; Villagra, Alejandro; Sotomayor, Eduardo M; Kozikowski, Alan P

    2012-11-26

    The incidence of malignant melanoma has dramatically increased in recent years thus requiring the need for improved therapeutic strategies. In our efforts to design selective histone deactylase inhibitors (HDACI), we discovered that the aryl urea 1 is a modestly potent yet nonselective inhibitor. Structure-activity relationship studies revealed that adding substituents to the nitrogen atom of the urea so as to generate compounds bearing a branched linker group results in increased potency and selectivity for HDAC6. Compound 5 g shows low nanomolar inhibitory potency against HDAC6 and a selectivity of ∼600-fold relative to the inhibition of HDAC1. These HDACIs were evaluated for their ability to inhibit the growth of B16 melanoma cells with the most potent and selective HDAC6I being found to decrease tumor cell growth. To the best of our knowledge, this work constitutes the first report of HDAC6-selective inhibitors that possess antiproliferative effects against melanoma cells.

  2. Selective histone deacetylase 6 inhibitors bearing substituted urea linkers inhibit melanoma cell growth

    PubMed Central

    Bergman, Joel A.; Woan, Karrune; Perez-Villarroel, Patricio; Villagra, Alejandro; Sotomayor, Eduardo M.; Kozikowski, Alan P.

    2012-01-01

    The incidence of malignant melanoma has dramatically increased in recent years thus requiring the need for improved therapeutic strategies. In our efforts to design selective histone deactylase inhibitors (HDACI), we discovered that the aryl urea 1 is a modestly potent yet non-selective inhibitor. Structure activity relationship studies revealed that adding substituents to the nitrogen atom of the urea so as to generate compounds bearing a branched linker group results in increased potency and selectivity for HDAC6. Compound 5g shows low nanomolar inhibitory potency against HDAC6 and a selectivity of ~600-fold relative to the inhibition of HDAC1. These HDACIs were evaluated for their ability to inhibit the growth of B16 melanoma cells with the most potent and selective HDAC6I being found to decrease tumor cell growth. To the best of our knowledge, this work constitutes the first report of HDAC6 selective inhibitors that possess antiproliferative effects against melanoma cells. PMID:23009203

  3. A novel bipartite nuclear localization signal with an atypically long linker in DOF transcription factors.

    PubMed

    Krebs, Jonas; Mueller-Roeber, Bernd; Ruzicic, Slobodan

    2010-05-01

    Large molecules require a nuclear localization signal (NLS) for translocation into the nucleus. Classical NLSs are rich in basic amino acids and they represent three groups, based on their structural features: SV40 T-antigen-type, yeast mating factor Matalpha-2-type, and bipartite NLSs. DNA-binding-with-one-finger (DOF) transcription factors play important roles in plants, and although their nuclear localization has been demonstrated in several cases, public protein localization prediction tools fail to detect NLS motifs in these proteins. Here, we demonstrate that an atypical bipartite NLS with a 17 amino acid long linker between its flanking basic regions directs Arabidopsis thaliana DOF proteins to the cell nucleus. The novel bipartite NLS is highly conserved in plant DOF transcription factors, including the single DOF protein in the green alga Chlamydomonas reinhardtii.

  4. The linker histone H1.0 generates epigenetic and functional intratumor heterogeneity*

    PubMed Central

    Burney, Matthew J.; Patel, Harshil; Henser-Brownhill, Tristan; Cohen, Ayelet-Hashahar Shapira; Li, Yilong; Ben-Hamo, Rotem; Nye, Emma; Spencer-Dene, Bradley; Chakravarty, Probir; Efroni, Sol; Matthews, Nik; Misteli, Tom; Meshorer, Eran; Scaffidi, Paola

    2016-01-01

    Tumors comprise functionally diverse subpopulations of cells with distinct proliferative potential. Here, we show that dynamic epigenetic states defined by the linker histone H1.0 determine which cells within a tumor can sustain the long-term cancer growth. Numerous cancer types exhibit high inter- and intratumor heterogeneity of H1.0, with H1.0 levels correlating with tumor differentiation status, patient survival and, at the single-cell level, cancer stem cell markers. Silencing of H1.0 promotes maintenance of self-renewing cells by inducing de-repression of megabase-sized gene domains harboring downstream effectors of oncogenic pathways. Self-renewing epigenetic states are not stable and re-expression of H1.0 in subsets of tumor cells establishes transcriptional programs that restrict cancer cell long-term proliferative potential and drive their differentiation. Our results uncover epigenetic determinants of tumor-maintaining cells. PMID:27708074

  5. Substructuring of multibody systems for numerical transfer path analysis in internal combustion engines

    NASA Astrophysics Data System (ADS)

    Acri, Antonio; Offner, Guenter; Nijman, Eugene; Rejlek, Jan

    2016-10-01

    Noise legislations and the increasing customer demands determine the Noise Vibration and Harshness (NVH) development of modern commercial vehicles. In order to meet the stringent legislative requirements for the vehicle noise emission, exact knowledge of all vehicle noise sources and their acoustic behavior is required. Transfer path analysis (TPA) is a fairly well established technique for estimating and ranking individual low-frequency noise or vibration contributions via the different transmission paths. Transmission paths from different sources to target points of interest and their contributions can be analyzed by applying TPA. This technique is applied on test measurements, which can only be available on prototypes, at the end of the designing process. In order to overcome the limits of TPA, a numerical transfer path analysis methodology based on the substructuring of a multibody system is proposed in this paper. Being based on numerical simulation, this methodology can be performed starting from the first steps of the designing process. The main target of the proposed methodology is to get information of noise sources contributions of a dynamic system considering the possibility to have multiple forces contemporary acting on the system. The contributions of these forces are investigated with particular focus on distribute or moving forces. In this paper, the mathematical basics of the proposed methodology and its advantages in comparison with TPA will be discussed. Then, a dynamic system is investigated with a combination of two methods. Being based on the dynamic substructuring (DS) of the investigated model, the methodology proposed requires the evaluation of the contact forces at interfaces, which are computed with a flexible multi-body dynamic (FMBD) simulation. Then, the structure-borne noise paths are computed with the wave based method (WBM). As an example application a 4-cylinder engine is investigated and the proposed methodology is applied on the

  6. Linker Flexibility Facilitates Module Exchange in Fungal Hybrid PKS-NRPS Engineering

    PubMed Central

    Nielsen, Maria Lund; Isbrandt, Thomas; Petersen, Lene Maj; Mortensen, Uffe Hasbro; Andersen, Mikael Rørdam; Hoof, Jakob Blæsbjerg; Larsen, Thomas Ostenfeld

    2016-01-01

    Polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) each give rise to a vast array of complex bioactive molecules with further complexity added by the existence of natural PKS-NRPS fusions. Rational genetic engineering for the production of natural product derivatives is desirable for the purpose of incorporating new functionalities into pre-existing molecules, or for optimization of known bioactivities. We sought to expand the range of natural product diversity by combining modules of PKS-NRPS hybrids from different hosts, hereby producing novel synthetic natural products. We succeeded in the construction of a functional cross-species chimeric PKS-NRPS expressed in Aspergillus nidulans. Module swapping of the two PKS-NRPS natural hybrids CcsA from Aspergillus clavatus involved in the biosynthesis of cytochalasin E and related Syn2 from rice plant pathogen Magnaporthe oryzae lead to production of novel hybrid products, demonstrating that the rational re-design of these fungal natural product enzymes is feasible. We also report the structure of four novel pseudo pre-cytochalasin intermediates, niduclavin and niduporthin along with the chimeric compounds niduchimaeralin A and B, all indicating that PKS-NRPS activity alone is insufficient for proper assembly of the cytochalasin core structure. Future success in the field of biocombinatorial synthesis of hybrid polyketide-nonribosomal peptides relies on the understanding of the fundamental mechanisms of inter-modular polyketide chain transfer. Therefore, we expressed several PKS-NRPS linker-modified variants. Intriguingly, the linker anatomy is less complex than expected, as these variants displayed great tolerance with regards to content and length, showing a hitherto unreported flexibility in PKS-NRPS hybrids, with great potential for synthetic biology-driven biocombinatorial chemistry. PMID:27551732

  7. Cytoskeletal Linker Protein Dystonin Is Not Critical to Terminal Oligodendrocyte Differentiation or CNS Myelination

    PubMed Central

    Bonin, Sawyer R.; Gibeault, Sabrina; De Repentigny, Yves; Kothary, Rashmi

    2016-01-01

    Oligodendrocyte differentiation and central nervous system myelination require massive reorganization of the oligodendrocyte cytoskeleton. Loss of specific actin- and tubulin-organizing factors can lead to impaired morphological and/or molecular differentiation of oligodendrocytes, resulting in a subsequent loss of myelination. Dystonin is a cytoskeletal linker protein with both actin- and tubulin-binding domains. Loss of function of this protein results in a sensory neuropathy called Hereditary Sensory Autonomic Neuropathy VI in humans and dystonia musculorum in mice. This disease presents with severe ataxia, dystonic muscle and is ultimately fatal early in life. While loss of the neuronal isoforms of dystonin primarily leads to sensory neuron degeneration, it has also been shown that peripheral myelination is compromised due to intrinsic Schwann cell differentiation abnormalities. The role of this cytoskeletal linker in oligodendrocytes, however, remains unclear. We sought to determine the effects of the loss of neuronal dystonin on oligodendrocyte differentiation and central myelination. To address this, primary oligodendrocytes were isolated from a severe model of dystonia musculorum, Dstdt-27J, and assessed for morphological and molecular differentiation capacity. No defects could be discerned in the differentiation of Dstdt-27J oligodendrocytes relative to oligodendrocytes from wild-type littermates. Survival was also compared between Dstdt-27J and wild-type oligodendrocytes, revealing no significant difference. Using a recently developed migration assay, we further analysed the ability of primary oligodendrocyte progenitor cell motility, and found that Dstdt-27J oligodendrocyte progenitor cells were able to migrate normally. Finally, in vivo analysis of oligodendrocyte myelination was done in phenotype-stage optic nerve, cerebral cortex and spinal cord. The density of myelinated axons and g-ratios of Dstdt-27J optic nerves was normal, as was myelin basic

  8. Effect of Biointerfacing Linker Chemistries on the Sensitivity of Silicon Nanowires for Protein Detection

    PubMed Central

    Dorvel, Brian; Reddy, Bobby; Bashir, Rashid

    2013-01-01

    Point-of-care diagnostics show promise in removing reliance on centralized lab testing facilities, and may help increase both the survival rate for infectious diseases as well as monitoring of chronic illnesses. CMOS compatible diagnostic platforms are currently being considered possible solution as they can be easily miniaturized and can be cost-effective. Top-down fabricated silicon nanowires are a CMOS-compatible technology which have demonstrated high sensitivities in detecting biological analytes, such as proteins, DNA, and RNA. However, the reported response of nanowires to these analytes has varied widely since several different functionalization protocols have been attempted with little characterization and comparison. Here we report protocols for fabrication and functionalization of silicon nanowires which yield highly stable nanowires in aqueous solutions, and limits of detection to ~1pg/mL of the model protein used in the study. A thorough characterization was done into optimizing the release of the silicon nanowires using combined dry and wet etch techniques, which yielded nanowires that could be directly compared to increase output statistics. Moreover, a range of different linker chemistries were tried for reacting the primary antibody, and its response to target and non-specific antigens, with polyethylene glycol based linker BS(PEG)5 providing the best response. Consequently, this chemistry was used to characterize different oxide thicknesses and their responses to the mouse IgG antigen, which with the smallest oxide thickness yielded 0.1–1pg/mL limits of detection and a dynamic range over 3 orders of magnitude. PMID:24040958

  9. H-DROP: an SVM based helical domain linker predictor trained with features optimized by combining random forest and stepwise selection

    NASA Astrophysics Data System (ADS)

    Ebina, Teppei; Suzuki, Ryosuke; Tsuji, Ryotaro; Kuroda, Yutaka

    2014-08-01

    Domain linker prediction is attracting much interest as it can help identifying novel domains suitable for high throughput proteomics analysis. Here, we report H-DROP, an SVM-based Helical Domain linker pRediction using OPtimal features. H-DROP is, to the best of our knowledge, the first predictor for specifically and effectively identifying helical linkers. This was made possible first because a large training dataset became available from IS-Dom, and second because we selected a small number of optimal features from a huge number of potential ones. The training helical linker dataset, which included 261 helical linkers, was constructed by detecting helical residues at the boundary regions of two independent structural domains listed in our previously reported IS-Dom dataset. 45 optimal feature candidates were selected from 3,000 features by random forest, which were further reduced to 26 optimal features by stepwise selection. The prediction sensitivity and precision of H-DROP were 35.2 and 38.8 %, respectively. These values were over 10.7 % higher than those of control methods including our previously developed DROP, which is a coil linker predictor, and PPRODO, which is trained with un-differentiated domain boundary sequences. Overall, these results indicated that helical linkers can be predicted from sequence information alone by using a strictly curated training data set for helical linkers and carefully selected set of optimal features. H-DROP is available at http://domserv.lab.tuat.ac.jp.

  10. Modulations of DNA Contacts by Linker Histones and Post-translational Modifications Determine the Mobility and Modifiability of Nucleosomal H3 Tails.

    PubMed

    Stützer, Alexandra; Liokatis, Stamatios; Kiesel, Anja; Schwarzer, Dirk; Sprangers, Remco; Söding, Johannes; Selenko, Philipp; Fischle, Wolfgang

    2016-01-21

    Post-translational histone modifications and linker histone incorporation regulate chromatin structure and genome activity. How these systems interface on a molecular level is unclear. Using biochemistry and NMR spectroscopy, we deduced mechanistic insights into the modification behavior of N-terminal histone H3 tails in different nucleosomal contexts. We find that linker histones generally inhibit modifications of different H3 sites and reduce H3 tail dynamics in nucleosomes. These effects are caused by modulations of electrostatic interactions of H3 tails with linker DNA and largely depend on the C-terminal domains of linker histones. In agreement, linker histone occupancy and H3 tail modifications segregate on a genome-wide level. Charge-modulating modifications such as phosphorylation and acetylation weaken transient H3 tail-linker DNA interactions, increase H3 tail dynamics, and, concomitantly, enhance general modifiability. We propose that alterations of H3 tail-linker DNA interactions by linker histones and charge-modulating modifications execute basal control mechanisms of chromatin function.

  11. Distribution of distances between dislocations in different types of dislocation substructures in deformed Cu-Al alloys

    SciTech Connect

    Trishkina, L. Zboykova, N.; Koneva, N. Kozlov, E.; Cherkasova, T.

    2016-01-15

    The aim of the investigation was the determination of the statistic description of dislocation distribution in each dislocation substructures component forming after different deformation degrees in the Cu-Al alloys. The dislocation structures were investigated by the transmission diffraction electron microscopy method. In the work the statistic description of distance distribution between the dislocations, dislocation barriers and dislocation tangles in the deformed Cu-Al alloys with different concentration of Al and test temperature at the grain size of 100 µm was carried out. It was established that the above parameters influence the dislocation distribution in different types of the dislocation substructures (DSS): dislocation chaos, dislocation networks without disorientation, nondisoriented and disoriented cells, in the walls and inside the cells. The distributions of the distances between dislocations in the investigated alloys for each DSS type formed at certain deformation degrees and various test temperatures were plotted.

  12. Linker histone H1 is present in centromeric chromatin of living human cells next to inner kinetochore proteins

    PubMed Central

    Orthaus, S.; Klement, K.; Happel, N.; Hoischen, C.; Diekmann, S.

    2009-01-01

    The vertebrate kinetochore complex assembles at the centromere on α-satellite DNA. In humans, α-satellite DNA has a repeat length of 171 bp slightly longer than the DNA in the chromatosome containing the linker histone H1. The centromere-binding protein CENP-B binds specifically to α-satellite DNA with properties of a centromeric-linker histone. Here, we analysed if linker histone H1 is present at or excluded from centromeric chromatin by CENP-B. By immunostaining we detected the presence, but no enrichment or depletion of five different H1 subtypes at centromeric chromatin. The binding dynamics of H1 at centromeric sites were similar to that at other locations in the genome. These dynamics did not change in CENP-B depleted cells, suggesting that CENP-B and H1 co-exist in centromeric chromatin with no or little functional overlap. By bimolecular fluorescence complementation (BiFC) and Förster resonance energy transfer (FRET), we revealed that the linker histone H1 subtypes H1° and H1.2 bind to centromeric chromatin in interphase nuclei in direct neighbourhood to inner kinetochore proteins. PMID:19336418

  13. Extremely stretchable thermosensitive hydrogels by introducing slide-ring polyrotaxane cross-linkers and ionic groups into the polymer network

    PubMed Central

    Bin Imran, Abu; Esaki, Kenta; Gotoh, Hiroaki; Seki, Takahiro; Ito, Kohzo; Sakai, Yasuhiro; Takeoka, Yukikazu

    2014-01-01

    Stimuli-sensitive hydrogels changing their volumes and shapes in response to various stimulations have potential applications in multiple fields. However, these hydrogels have not yet been commercialized due to some problems that need to be overcome. One of the most significant problems is that conventional stimuli-sensitive hydrogels are usually brittle. Here we prepare extremely stretchable thermosensitive hydrogels with good toughness by using polyrotaxane derivatives composed of α-cyclodextrin and polyethylene glycol as cross-linkers and introducing ionic groups into the polymer network. The ionic groups help the polyrotaxane cross-linkers to become well extended in the polymer network. The resulting hydrogels are surprisingly stretchable and tough because the cross-linked α-cyclodextrin molecules can move along the polyethylene glycol chains. In addition, the polyrotaxane cross-linkers can be used with a variety of vinyl monomers; the mechanical properties of the wide variety of polymer gels can be improved by using these cross-linkers. PMID:25296246

  14. Phenyl amide linker improves the pharmacokinetics and pharmacodynamics of N-terminally mono-PEGylated human growth hormone.

    PubMed

    Wu, Ling; Ji, Shaoyang; Shen, Lijuan; Hu, Tao

    2014-09-02

    Human growth hormone (hGH) suffers from a short plasma half-life of ∼15 min, necessitating frequent injections to maintain its physiological effect. PEGylation, conjugation of polyethylene glycol (PEG), is an effective strategy to prolong the plasma half-life of hGH. However, PEGylation can significantly decrease the bioactivity of hGH. Thus, a new PEGylation approach is desired to improve the pharmacokinetics (PK) and pharmacodynamics (PD) of the PEGylated hGH. In the present study, two N-terminally mono-PEGylated hGHs were prepared using aldehyde chemistry. Phenyl amide and ethyl moieties were used as the linkers between PEG and hGH, respectively. The hydrodynamic volume, proteolytic sensitivity, and immunogenicity of the PEGylated hGH with phenyl amide linker (hGH-phenyl-PEG) were lower than those of the one with propyl linker (hGH-prop-PEG). In addition, hGH-phenyl-PEG showed a higher in vitro bioactivity and better PK and PD than hGH-prop-PEG. The better PK of hGH-phenyl-PEG was mainly due to its lower proteolytic sensitivity and low immunogenicity. The better PD of hGH-phenyl-PEG was mainly due to its higher in vitro bioactivity. Thus, the phenyl amide linker can improve the overall pharmacological profiles of the PEGylated hGH. Our study is expected to advance the development of long-acting protein biotherapeutics with high therapeutic efficacy.

  15. Mad linker phosphorylations control the intensity and range of the BMP-activity gradient in developing Drosophila tissues

    PubMed Central

    Aleman, Abigail; Rios, Marlyn; Juarez, Matthew; Lee, Daniel; Chen, Annan; Eivers, Edward

    2014-01-01

    The BMP ligand Dpp, operates as a long range morphogen to control many important functions during Drosophila development from tissue patterning to growth. The BMP signal is transduced intracellularly via C-terminal phosphorylation of the BMP transcription factor Mad, which forms an activity gradient in developing embryonic tissues. Here we show that Cyclin dependent kinase 8 and Shaggy phosphorylate three Mad linker serines. We demonstrate that linker phosphorylations control the peak intensity and range of the BMP signal across rapidly developing embryonic tissues. Shaggy knockdown broadened the range of the BMP-activity gradient and increased high threshold target gene expression in the early embryo, while expression of a Mad linker mutant in the wing disc resulted in enhanced levels of C-terminally phosphorylated Mad, a 30% increase in wing tissue, and elevated BMP target genes. In conclusion, our results describe how Mad linker phosphorylations work to control the peak intensity and range of the BMP signal in rapidly developing Drosophila tissues. PMID:25377173

  16. Efficient synthesis of diverse heterobifunctionalized clickable oligo(ethylene glycol) linkers: potential applications in bioconjugation and targeted drug delivery.

    PubMed

    Goswami, Lalit N; Houston, Zachary H; Sarma, Saurav J; Jalisatgi, Satish S; Hawthorne, M Frederick

    2013-02-21

    Herein we describe the sequential synthesis of a variety of azide-alkyne click chemistry-compatible heterobifunctional oligo(ethylene glycol) (OEG) linkers for bioconjugation chemistry applications. Synthesis of these bioorthogonal linkers was accomplished through desymmetrization of OEGs by conversion of one of the hydroxyl groups to either an alkyne or azido functionality. The remaining distal hydroxyl group on the OEGs was activated by either a 4-nitrophenyl carbonate or a mesylate (-OMs) group. The -OMs functional group served as a useful precursor to form a variety of heterobifunctionalized OEG linkers containing different highly reactive end groups, e.g., iodo, -NH(2), -SH and maleimido, that were orthogonal to the alkyne or azido functional group. Also, the alkyne- and azide-terminated OEGs are useful for generating larger discrete poly(ethylene glycol) (PEG) linkers (e.g., PEG(16) and PEG(24)) by employing a Cu(I)-catalyzed 1,3-dipolar cycloaddition click reaction. The utility of these clickable heterobifunctional OEGs in bioconjugation chemistry was demonstrated by attachment of the integrin (α(v)β(3)) receptor targeting peptide, cyclo-(Arg-Gly-Asp-D-Phe-Lys) (cRGfKD) and to the fluorescent probe sulfo-rhodamine B. The synthetic methodology presented herein is suitable for the large scale production of several novel heterobifunctionalized OEGs from readily available and inexpensive starting materials.

  17. Mutations in the linker domain affect phospho-STAT3 function and suggest targets for interrupting STAT3 activity.

    PubMed

    Mertens, Claudia; Haripal, Bhagwattie; Klinge, Sebastian; Darnell, James E

    2015-12-01

    Crystallography of the cores of phosphotyrosine-activated dimers of STAT1 (132-713) and STAT3 (127-722) bound to a similar double-stranded deoxyoligonucleotide established the domain structure of the STATs and the structural basis for activation through tyrosine phosphorylation and dimerization. We reported earlier that mutants in the linker domain of STAT1 that connect the DNA-binding domain and SH2 domain can prevent transcriptional activation. Because of the pervasive importance of persistently activated STAT3 in many human cancers and the difficulty of finding useful drug candidates aimed at disrupting the pY interchange in active STAT3 dimers, we have examined effects of an array of mutants in the STAT3 linker domain. We have found several STAT3 linker domain mutants to have profound effects of inhibiting STAT3 transcriptional activation. From these results, we propose (i) there is definite functional interaction of the linker both with the DNA binding domain and with the SH2 domain, and (ii) these putative contacts provide potential new targets for small molecule-induced pSTAT3 inhibition.

  18. Mutations in the linker domain affect phospho-STAT3 function and suggest targets for interrupting STAT3 activity

    PubMed Central

    Mertens, Claudia; Haripal, Bhagwattie; Klinge, Sebastian; Darnell, James E.

    2015-01-01

    Crystallography of the cores of phosphotyrosine-activated dimers of STAT1 (132–713) and STAT3 (127–722) bound to a similar double-stranded deoxyoligonucleotide established the domain structure of the STATs and the structural basis for activation through tyrosine phosphorylation and dimerization. We reported earlier that mutants in the linker domain of STAT1 that connect the DNA-binding domain and SH2 domain can prevent transcriptional activation. Because of the pervasive importance of persistently activated STAT3 in many human cancers and the difficulty of finding useful drug candidates aimed at disrupting the pY interchange in active STAT3 dimers, we have examined effects of an array of mutants in the STAT3 linker domain. We have found several STAT3 linker domain mutants to have profound effects of inhibiting STAT3 transcriptional activation. From these results, we propose (i) there is definite functional interaction of the linker both with the DNA binding domain and with the SH2 domain, and (ii) these putative contacts provide potential new targets for small molecule-induced pSTAT3 inhibition. PMID:26553978

  19. Half-life extension of the HIV-fusion inhibitor peptide TRI-1144 using a novel linker technology.

    PubMed

    Schneider, Eric L; Ashley, Gary W; Dillen, Lieve; Stoops, Bart; Austin, Nigel E; Malcolm, Bruce A; Santi, Daniel V

    2015-06-01

    We have previously developed a linker technology for half-life extension of peptides, proteins and small molecule drugs (1). The linkers undergo β-elimination reactions with predictable cleavage rates to release the native drug. Here we utilize this technology for half-life extension of the 38 amino acid HIV-1 fusion inhibitor TRI-1144. Conjugation of TRI-1144 to 40 kDa PEG by an appropriate β-eliminative linker and i.v. administration of the conjugate increased the in vivo half-life of the released peptide from 4 to 34 h in the rat, and the pharmacokinetic parameters were in excellent accord with a one-compartment model. From these data we simulated the pharmacokinetics of the PEG-TRI-1144 conjugate in humans, predicting a t1/2,β of 70 h for the released peptide, and that a serum concentration of 25 nM could be maintained by weekly doses of 8 μmol of the conjugate. Using a non-circulating carrier (2) similar simulations indicated a t1/2,β of 150 h for the peptide released from the conjugate and that dosing of only 1.8 μmol/week could maintain serum concentrations of TRI-1144 above 25 nM. Hence, releasable β-eliminative linkers provide significant half-life extension to TRI-1144 and would be expected to do likewise for related peptides.

  20. A simple modular aptasensor platform utilizing cucurbit[7]uril and a ferrocene derivative as an ultrastable supramolecular linker.

    PubMed

    Lee, Don-Wook; Park, Kyeng Min; Gong, Bokyoung; Shetty, Dinesh; Khedkar, Jayshree K; Baek, Kangkyun; Kim, Jeehong; Ryu, Sung Ho; Kim, Kimoon

    2015-02-21

    A simple modular aptamer-based sensor (aptasensor) platform was prepared by combining the merits of the rapid and efficient preparation of a self-assembled monolayer of cucurbit[7]uril (CB[7] SAM) and the strong and specific binding affinity of CB[7] to ferrocenemethylammonium (FA), as an ultrastable supramolecular linker, to immobilize aptamers on CB[7] SAM.

  1. Searching for dwarf spheroidal galaxies and other galactic dark matter substructures with the Fermi large area telescope

    SciTech Connect

    Drlica-Wagner, Alex

    2013-08-01

    Over the past century, it has become clear that about a quarter of the known universe is composed of an invisible, massive component termed ''dark matter''. Some of the most popular theories of physics beyond the Standard Model suggest that dark matter may be a new fundamental particle that could self-annihilate to produce γ rays. Nearby over-densities in the dark matter halo of our Milky Way present some of the most promising targets for detecting the annihilation of dark matter. We used the Large Area Telescope (LAT) on-board the Fermi Gamma-ray Space Telescope to search for γ rays produced by dark matter annihilation in Galactic dark matter substructures. We searched for γ-ray emission coincident with Milky Way dwarf spheroidal satellite galaxies, which trace the most massive Galactic dark matter substructures. We also sought to identify nearby dark matter substructures that lack all astrophysical tracers and would be detectable only through γ-ray emission from dark matter annihilation. We found no conclusive evidence for γ-ray emission from dark matter annihilation, and we set stringent and robust constraints on the dark matter annihilation cross section. While γ-ray searches for dark matter substructure are currently the most sensitive and robust probes of dark matter annihilation, they are just beginning to intersect the theoretically preferred region of dark matter parameter space. Thus, we consider future prospects for increasing the sensitivity of γ-ray searches through improvements to the LAT instrument performance and through upcoming wide- field optical surveys.

  2. THE ONGOING ASSEMBLY OF A CENTRAL CLUSTER GALAXY: PHASE-SPACE SUBSTRUCTURES IN THE HALO OF M87

    SciTech Connect

    Romanowsky, Aaron J.; Brodie, Jean P.; Arnold, Jacob A.; Strader, Jay; Mihos, J. Christopher; Spitler, Lee R.; Forbes, Duncan A.; Foster, Caroline

    2012-03-20

    The halos of galaxies preserve unique records of their formation histories. We carry out the first combined observational and theoretical study of phase-space halo substructure in an early-type galaxy: M87, the central galaxy in the Virgo cluster. We analyze an unprecedented wide-field, high-precision photometric and spectroscopic data set for 488 globular clusters (GCs), which includes new, large-radius Subaru/Suprime-Cam and Keck/DEIMOS observations. We find signatures of two substructures in position-velocity phase space. One is a small, cold stream associated with a known stellar filament in the outer halo; the other is a large shell-like pattern in the inner halo that implies a massive, hitherto unrecognized accretion event. We perform extensive statistical tests and independent metallicity analyses to verify the presence and characterize the properties of these features, and to provide more general methodologies for future extragalactic studies of phase-space substructure. The cold outer stream is consistent with a dwarf galaxy accretion event, while for the inner shell there is tension between a low progenitor mass implied by the cold velocity dispersion, and a high mass from the large number of GCs, which might be resolved by a {approx}0.5 L* E/S0 progenitor. We also carry out proof-of-principle numerical simulations of the accretion of smaller galaxies in an M87-like gravitational potential. These produce analogous features to the observed substructures, which should have observable lifetimes of {approx}1 Gyr. The shell and stream GCs together support a scenario where the extended stellar envelope of M87 has been built up by a steady rain of material that continues until the present day. This phase-space method demonstrates unique potential for detailed tests of galaxy formation beyond the Local Group.

  3. Near-field cosmology with RR Lyrae variable stars: A first view of substructure in the southern sky

    NASA Astrophysics Data System (ADS)

    Duffau, S.; Vivas, A. K.; Navarrete, C.; Catelan, M.; Hajdu, G.; Torrealba, G.; Cortes, C.; Belokurov, V.; Koposov, S.; Drake, A. J.

    2016-05-01

    We present an update of a spectroscopic follow-up survey at low- resolution of a large number of RR Lyrae halo overdensity candidates found in the southern sky. The substructure candidates were identified in the RR Lyrae catalog of Torrealba et al. (2015) using Catalina Real-time Transient Survey (CRTS) data. Radial velocities and mean metallicities have been estimated for target stars in almost half of the original overdensities to assess their potential membership to coherent halo features.

  4. THE BOLOCAM GALACTIC PLANE SURVEY. XI. TEMPERATURES AND SUBSTRUCTURE OF GALACTIC CLUMPS BASED ON 350 μM OBSERVATIONS

    SciTech Connect

    Merello, Manuel; Evans II, Neal J.; Shirley, Yancy L.; Rosolowsky, Erik; Ginsburg, Adam; Bally, John; Battersby, Cara; Dunham, Michael M.

    2015-05-15

    We present 107 maps of continuum emission at 350 μm from Galactic molecular clumps. Observed sources were mainly selected from the Bolocam Galactic Plane Survey (BGPS) catalog, with three additional maps covering star-forming regions in the outer Galaxy. The higher resolution of the SHARC-II images (8.″5 beam) compared with the 1.1 mm images from BGPS (33″ beam) allowed us to identify a large population of smaller substructures within the clumps. A catalog is presented for the 1386 sources extracted from the 350 μm maps. The color temperature distribution of clumps based on the two wavelengths has a median of 13.3 K and mean of 16.3 ± 0.4 K, assuming an opacity law index of 1.7. For the structures with good determination of color temperatures, the mean ratio of gas temperature, determined from NH{sub 3} observations, to dust color temperature is 0.88 and the median ratio is 0.76. About half the clumps have more than 2 substructures and 22 clumps have more than 10. The fraction of the mass in dense substructures seen at 350 μm compared to the mass of their parental clump is ∼0.19, and the surface densities of these substructures are, on average, 2.2 times those seen in the clumps identified at 1.1 mm. For a well-characterized sample, 88 structures (31%) exceed a surface density of 0.2 g cm{sup −2}, and 18 (6%) exceed 1.0 g cm{sup −2}, thresholds for massive star formation suggested by theorists.

  5. Arc statistics with realistic cluster potentials. 2: Influence of cluster asymmetry and substructure

    NASA Astrophysics Data System (ADS)

    Bartelmann, Matthias; Steinmetz, Matthias; Weiss, Achim

    1995-05-01

    We construct a sample of numerical models for clusters of galaxies and employ these to investigate their capabilities of imaging background sources into long arcs. Emphasis is laid on the statistics of these arcs. We study cross sections for arc length and length-to-width ratio and optical depths for these arc properties, we examine the distribution of arc widths and curvature radii among long arcs, and we compare these reuslts to predictions based on simplified (radially symmetric) cluster models. We find that the capability of the numerically modeled clusters to produce long arcs is larger by about two orders of magnitude than that of spherically symmtric cluster models with the same observable parameters (core radii and velocity dispersions), and that they are similary efficient as singular isothermal spheres with the same velocity-dispersion distribution. The influence of source ellipticity is also investigated; we find that the optical depth for arcs with a length-to-width ratio greater than approximately 10 is significantly larger for elliptical than for circular sources. Given these results, we conclude that spherically symmetic lens models for galaxy clusters, adapted to the observable parameters of these clusters, grossly underestimate the frequency of long arcs. We attribute this difference between numerically constructed and simplified analytical lens models to the abundance and the extent of intrinsic asymmetry and to substructure in galaxy clusters.

  6. Kin in space: social viscosity in a spatially and genetically substructured network

    PubMed Central

    Wolf, Jochen B.W; Trillmich, Fritz

    2008-01-01

    Population substructuring is a fundamental aspect of animal societies. A growing number of theoretical studies recognize that who-meets-whom is not random, but rather determined by spatial relationships or illustrated by social networks. Structural properties of large highly dynamic social systems are notoriously difficult to unravel. Network approaches provide powerful ways to analyse the intricate relationships between social behaviour, dispersal strategies and genetic structure. Applying network analytical tools to a colony of the highly gregarious Galápagos sea lion (Zalophus wollebaeki), we find several genetic clusters that correspond to spatially determined ‘network communities’. Overall relatedness was low, and genetic structure in the network can be interpreted as an emergent property of philopatry and seems not to be primarily driven by targeted interactions among highly related individuals in family groups. Nevertheless, social relationships between directly adjacent individuals in the network were stronger among genetically more similar individuals. Taken together, these results suggest that even small differences in the degree of relatedness can influence behavioural decisions. This raises the fascinating prospect that kin selection may also apply to low levels of relatedness within densely packed animal groups where less obvious co-operative interactions such as increased tolerance and stress reduction are important. PMID:18522913

  7. Natural Product-Derived Spirooxindole Fragments Serve as Privileged Substructures for Discovery of New Anticancer Agents.

    PubMed

    Yu, Bin; Zheng, Yi-Chao; Shi, Xiao-Jing; Qi, Ping-Ping; Liu, Hong-Min

    2016-01-01

    The utility of natural products for identifying anticancer agents has been highly pursued in the last decades and over 100 drug molecules in clinic are natural products or natural product-derived compounds. Natural products are believed to be able to cover unexplored chemical space that is normally not occupied by commercially available molecule libraries. However, the low abundance and synthetic intractability of natural products have limited their applications in drug discovery. Recently, the identification of biologically relevant fragments derived from biologically validated natural products has been recognized as a powerful strategy in searching new biological probes and drugs. The spirocyclic oxindoles, as privileged structural scaffolds, have shown their potential in designing new drugs. Several anticancer drug candidates such as SAR405838, RO8994, CFI-400945 and their bioisosteres are undergoing clinical trials or preclinical studies. To highlight the significant progress, we focus on illustrating the discovery of SAR405838, RO8994, CFI-400945 and their bioisosteres for cancer therapy using substructure-based strategies and discussing modes of action, binding models and preclinical data.

  8. Jet substructure classification in high-energy physics with deep neural networks

    NASA Astrophysics Data System (ADS)

    Baldi, Pierre; Bauer, Kevin; Eng, Clara; Sadowski, Peter; Whiteson, Daniel

    2016-05-01

    At the extreme energies of the Large Hadron Collider, massive particles can be produced at such high velocities that their hadronic decays are collimated and the resulting jets overlap. Deducing whether the substructure of an observed jet is due to a low-mass single particle or due to multiple decay objects of a massive particle is an important problem in the analysis of collider data. Traditional approaches have relied on expert features designed to detect energy deposition patterns in the calorimeter, but the complexity of the data make this task an excellent candidate for the application of machine learning tools. The data collected by the detector can be treated as a two-dimensional image, lending itself to the natural application of image classification techniques. In this work, we apply deep neural networks with a mixture of locally connected and fully connected nodes. Our experiments demonstrate that without the aid of expert features, such networks match or modestly outperform the current state-of-the-art approach for discriminating between jets from single hadronic particles and overlapping jets from pairs of collimated hadronic particles, and that such performance gains persist in the presence of pileup interactions.

  9. Analysis of shape memory alloy sensory particles for damage detection via substructure and continuum damage modeling

    NASA Astrophysics Data System (ADS)

    Bielefeldt, Brent R.; Benzerga, A. Amine; Hartl, Darren J.

    2016-04-01

    The ability to monitor and predict the structural health of an aircraft is of growing importance to the aerospace industry. Currently, structural inspections and maintenance are based upon experiences with similar aircraft operating in similar conditions. While effective, these methods are time-intensive and unnecessary if the aircraft is not in danger of structural failure. It is imagined that future aircraft will utilize non-destructive evaluation methods, allowing for the near real-time monitoring of structural health. A particularly interesting method involves utilizing the unique transformation response of shape memory alloy (SMA) particles embedded in an aircraft structure. By detecting changes in the mechanical and/or electromagnetic responses of embedded particles, operators could detect the formation or propagation of fatigue cracks in the vicinity of these particles. This work focuses on a finite element model of SMA particles embedded in an aircraft wing using a substructure modeling approach in which degrees of freedom are retained only at specified points of connection to other parts or the application of boundary conditions, greatly reducing computational cost. Previous work evaluated isolated particle response to a static crack to numerically demonstrate and validate this damage detection method. This paper presents the implementation of a damage model to account for crack propagation and examine for the first time the effect of particle configuration and/or relative placement with respect to the ability to detect damage.

  10. Size, shape and substructure of dust particles collected by the COSIMA instrument on board ROSETTA

    NASA Astrophysics Data System (ADS)

    Ligier, Nicolas; Langevin, Yves; Hilchenbach, Martin; Merouane, Sihane; Hornung, Klaus; Cosima Team

    2015-04-01

    The COSIMA instrument on-board ROSETTA is dedicated to the analysis by TOF mass spectrometry of cometary grains next collected in the inner coma of 67P/Churymov-Gerasimenko. The grains are collected simultaneously by three 10x10 mm targets exposed in front of an entry funnel. The targets are imaged at regular intervals by presenting them in front of a microscopic camera ("COSISCOPE") under grazing incidence illumination by two LED's on opposite sides of the observed target. The resolution of COSISCOPE (14 µm / pixel), makes it possible to optically characterize the particles which fill up a significant fraction of the chemically analyzed spot (50 µm FWHM). More than 2000 cometary dusts collected by six different targets have already been detected by the COSISCOPE in less than five months. The collected dust particles present a complex typology (presented by a companion abstract by Y. Langevin). In this contribution, we report the first results of an automatic optical characterization method for classifying the collected particles based on size, shape, shadows and substructure. These results will be used to infer the volume of parent particles which shattered upon collection.

  11. A Consensus Tree Approach for Reconstructing Human Evolutionary History and Detecting Population Substructure

    NASA Astrophysics Data System (ADS)

    Tsai, Ming-Chi; Blelloch, Guy; Ravi, R.; Schwartz, Russell

    The random accumulation of variations in the human genome over time implicitly encodes a history of how human populations have arisen, dispersed, and intermixed since we emerged as a species. Reconstructing that history is a challenging computational and statistical problem but has important applications both to basic research and to the discovery of genotype-phenotype correlations. In this study, we present a novel approach to inferring human evolutionary history from genetic variation data. Our approach uses the idea of consensus trees, a technique generally used to reconcile species trees from divergent gene trees, adapting it to the problem of finding the robust relationships within a set of intraspecies phylogenies derived from local regions of the genome. We assess the quality of the method on two large-scale genetic variation data sets: the HapMap Phase II and the Human Genome Diversity Project. Qualitative comparison to a consensus model of the evolution of modern human population groups shows that our inferences closely match our best current understanding of human evolutionary history. A further comparison with results of a leading method for the simpler problem of population substructure assignment verifies that our method provides comparable accuracy in identifying meaningful population subgroups in addition to inferring the relationships among them.

  12. SEXTANS' COLD SUBSTRUCTURES AS A DYNAMICAL JUDGE: CORE, CUSP, OR MOND?

    SciTech Connect

    Lora, V.; Grebel, E. K.; Just, A.; Sánchez-Salcedo, F. J.

    2013-11-01

    The cold dark matter model predicts cuspy dark matter (DM) halos. However, it has been found that in some low-mass galaxies, cored dark halos provide a better description of their internal dynamics. Here we give constraints on the dark halo profile in the Sextans dwarf spheroidal galaxy by studying the longevity of two cold kinematic substructures detected in this galaxy. We perform N-body simulations of a stellar clump in the Sextans dwarf galaxy, including a live DM halo and the main stellar component. We find that if the dark halo is cuspy, stellar clumps orbiting with semi-major axis ≈400 pc are disrupted in ∼5 Gyr, even if the clump is initially as compact stellar cluster with a radius of r{sub c} = 5 pc. Stellar clusters in an initial orbit with semi-major axis ≤250 pc may survive to dissolution, but their orbits decay toward the center by dynamical friction. In contrast, the stellar clumps can persist for a Hubble time within a cored DM halo, even if the initial clump's radius is as extended as r{sub c} = 80 pc. We also study the evolution of the clump in the MONDian context. In this scenario, we find that even an extended stellar clump with radius r{sub c} = 80 pc survives for a Hubble time, but an unrealistic value for the stellar mass-to-light ratio of 9.2 is needed.

  13. Exploring a heavy charged Higgs using jet substructure in a fully hadronic channel

    NASA Astrophysics Data System (ADS)

    Patrick, Riley; Sharma, Pankaj; Williams, Anthony G.

    2017-04-01

    In the framework of the type-II Two Higgs Doublet Model (2HDM-II) a charged Higgs search strategy is presented for the dominant production mode gb → tH± at the 14 TeV LHC. We consider the decay process which includes t → bW± and H± → AW±, and a fully hadronic final state consisting of bb b bar +jets + X. Dictated by the b → sγ constraints which render MH± > 480 GeV we study two scenarios in which the charged Higgs mass is 750 GeV and the pseudoscalar Higgs mass is 200 GeV and 500 GeV. In this mass scheme highly boosted final state objects are expected and handled with jet substructure techniques which also acts to suppress the standard model background. A detailed detector analysis is performed, followed by a multivariate analysis involving many kinematic variables to optimize signal to background significance. Finally the LHC search sensitivities for the two scenarios are presented for various integrated luminosities.

  14. Towards the development of micromechanics equations for ceramic matrix composites via fiber substructuring

    NASA Technical Reports Server (NTRS)

    Murthy, P. L. N.; Chamis, C. C.

    1992-01-01

    A generic unit cell model which includes a unique fiber substructuring concept is proposed for the development of micromechanics equations for continuous fiber reinforcement ceramic composites. The unit cell consists of three constituents: fiber, matrix, and an interphase. In the present approach, the unit cell is further subdivided into several slices and the equations of micromechanics are derived for each slice. These are subsequently integrated to obtain ply level properties. A stand alone computer code containing the micromechanics model as a module is currently being developed specifically for the analysis of ceramic matrix composites. Towards this development, equivalent ply property results for a SiC/Ti-15-3 composite with 0.5 fiber volume ratio are presented and compared with those obtained from customary micromechanics models to illustrate the concept. Also, comparisons with limited experimental data for the ceramic matrix composite, SiC/RBSN (Reaction Bonded Silicon Nitride) with a 0.3 fiber volume ratio are given to validate the concepts.

  15. Measuring the power spectrum of dark matter substructure using strong gravitational lensing

    NASA Astrophysics Data System (ADS)

    Hezaveh, Yashar; Dalal, Neal; Holder, Gilbert; Kisner, Theodore; Kuhlen, Michael; Perreault Levasseur, Laurence

    2016-11-01

    In recent years, it has become possible to detect individual dark matter subhalos near images of strongly lensed extended background galaxies. Typically, only the most massive subhalos in the strong lensing region may be detected this way. In this work, we show that strong lenses may also be used to constrain the much more numerous population of lower mass subhalos that are too small to be detected individually. In particular, we show that the power spectrum of projected density fluctuations in galaxy halos can be measured using strong gravitational lensing. We develop the mathematical framework of power spectrum estimation, and test our method on mock observations. We use our results to determine the types of observations required to measure the substructure power spectrum with high significance. We predict that deep observations (~10 hours on a single target) with current facilities can measure this power spectrum at the 3σ level, with no apparent degeneracy with unknown clumpiness in the background source structure or fluctuations from detector noise. Upcoming ALMA measurements of strong lenses are capable of placing strong constraints on the abundance of dark matter subhalos and the underlying particle nature of dark matter.

  16. Boosting the charged Higgs search prospects using jet substructure at the LHC

    NASA Astrophysics Data System (ADS)

    Li, Jinmian; Patrick, Riley; Sharma, Pankaj; Williams, Anthony G.

    2016-11-01

    Charged Higgs bosons are predicted in variety of theoretically well-motivated new physics models with extended Higgs sectors. In this study, we focus on a type-II two Higgs doublet model (2HDM-II) and consider a heavy charged Higgs with its mass ranging from 500 GeV to 1 TeV as dictated by the b → sγ constraints which render M H ± > 480 GeV. We study the dominant production mode H ± t associated production with H ± → W ± A being the dominant decay channel when the pseudoscalar A is considerably lighter. For such a heavy charged Higgs, both the decay products W ± and A are relatively boosted. In such a scenario, we apply the jet substructure analysis of tagging the fat pseudoscalar and W jets in order to eliminate the standard model background efficiently. We perform a detailed detector simulation for the signal and background processes at the 14 TeV LHC. We introduce various kinematical cuts to determine the signal significance for a number of benchmark points with charged Higgs boson mass from 500 GeV to 1 TeV in the W ± A decay channel. Finally we perform a multivariate analysis utilizing a boosted decision tree algorithm to optimize these significances.

  17. Probing Kinematic Substructures in the Virgo Overdensity using RR Lyrae from Recent Surveys

    NASA Astrophysics Data System (ADS)

    Farmer, John; Vivas, A. Katherina

    2015-01-01

    The Virgo Overdensity is one of the most intriguing features of the galactic halo, as it covers a large portion of the sky and seems to contain several kinematic substructures. It has been suggested that the remnants of several merger events coexist in this region. RR Lyrae stars are an excellent tracer for disentangling the different components of this overdensity, since they are excellent standard candles; by using both positions and pulsation-corrected radial velocities, we can identify distinct groups in phase space. In the last year, several surveys for RR Lyraes covering the Virgo region have become publicly available. We present analysis of ~300 spectra for ~200 stars in the Virgo overdensity region. This is a significant increase in the known sample of these stars in the region, spanning a significantly larger area of the sky than previous studies. Photometry for these data are taken primarily from the La Silla and Venezuela QUEST variability surveys with spectra provided by SDSS Data Release 10. Radial velocities for type ab RR Lyrae stars are corrected using the new set of template radial velocity curves for Balmer and metallic lines given by Sesar (2012). We combine data from QUEST, the Catalina Sky Survey, LINEAR, and spectroscopic observations from Duffau (2014) to give our full sample. A preliminary analysis reveals confirmation for several known stellar streams.

  18. Detecting mass substructure in galaxy clusters: an aperture mass statistic for gravitational flexion

    NASA Astrophysics Data System (ADS)

    Leonard, Adrienne; King, Lindsay J.; Wilkins, Stephen M.

    2009-05-01

    Gravitational flexion has been introduced as a technique by which one can map out and study substructure in clusters of galaxies. Previous analyses involving flexion have measured the individual galaxy-galaxy flexion signal, or used either parametric techniques or a Kaiser, Squires and Broadhurst (KSB)-type inversion to reconstruct the mass distribution in Abell 1689. In this paper, we present an aperture mass statistic for flexion, and apply it to the lensed images of background galaxies obtained by ray-tracing simulations through a simple analytic mass distribution and through a galaxy cluster from the Millennium Simulation. We show that this method is effective at detecting and accurately tracing structure within clusters of galaxies on subarcminute scales with high signal to noise even using a moderate background source number density and image resolution. In addition, the method provides much more information about both the overall shape and the small-scale structure of a cluster of galaxies than can be achieved through a weak lensing mass reconstruction using gravitational shear data. Lastly, we discuss how the zero-points of the aperture mass might be used to infer the masses of structures identified using this method.

  19. An ALMA Search for Substructure, Fragmentation, and Hidden Protostars in Starless Cores in Chamaeleon I

    NASA Astrophysics Data System (ADS)

    Dunham, Michael M.; Offner, Stella S. R.; Pineda, Jaime E.; Bourke, Tyler L.; Tobin, John J.; Arce, Héctor G.; Chen, Xuepeng; Di Francesco, James; Johnstone, Doug; Lee, Katherine I.; Myers, Philip C.; Price, Daniel; Sadavoy, Sarah I.; Schnee, Scott

    2016-06-01

    We present an Atacama Large Millimeter/submillimeter Array (ALMA) 106 GHz (Band 3) continuum survey of the complete population of dense cores in the Chamaeleon I molecular cloud. We detect a total of 24 continuum sources in 19 different target fields. All previously known Class 0 and Class I protostars in Chamaeleon I are detected, whereas all of the 56 starless cores in our sample are undetected. We show that the Spitzer+Herschel census of protostars in Chamaeleon I is complete, with the rate at which protostellar cores have been misclassified as starless cores calculated as <1/56, or <2%. We use synthetic observations to show that starless cores collapsing following the turbulent fragmentation scenario are detectable by our ALMA observations when their central densities exceed ˜108 cm-3, with the exact density dependent on the viewing geometry. Bonnor-Ebert spheres, on the other hand, remain undetected to central densities at least as high as 1010 cm-3. Our starless core non-detections are used to infer that either the star-formation rate is declining in Chamaeleon I and most of the starless cores are not collapsing, matching the findings of previous studies, or that the evolution of starless cores are more accurately described by models that develop less substructure than predicted by the turbulent fragmentation scenario, such as Bonnor-Ebert spheres. We outline future work necessary to distinguish between these two possibilities.

  20. Kin in space: social viscosity in a spatially and genetically substructured network.

    PubMed

    Wolf, Jochen B W; Trillmich, Fritz

    2008-09-22

    Population substructuring is a fundamental aspect of animal societies. A growing number of theoretical studies recognize that who-meets-whom is not random, but rather determined by spatial relationships or illustrated by social networks. Structural properties of large highly dynamic social systems are notoriously difficult to unravel. Network approaches provide powerful ways to analyse the intricate relationships between social behaviour, dispersal strategies and genetic structure. Applying network analytical tools to a colony of the highly gregarious Galápagos sea lion (Zalophus wollebaeki), we find several genetic clusters that correspond to spatially determined 'network communities'. Overall relatedness was low, and genetic structure in the network can be interpreted as an emergent property of philopatry and seems not to be primarily driven by targeted interactions among highly related individuals in family groups. Nevertheless, social relationships between directly adjacent individuals in the network were stronger among genetically more similar individuals. Taken together, these results suggest that even small differences in the degree of relatedness can influence behavioural decisions. This raises the fascinating prospect that kin selection may also apply to low levels of relatedness within densely packed animal groups where less obvious co-operative interactions such as increased tolerance and stress reduction are important.