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Sample records for linker substructure common

  1. Maximum common substructure-based data fusion in similarity searching.

    PubMed

    Duesbury, Edmund; Holliday, John; Willett, Peter

    2015-02-23

    Data fusion has been shown to work very well when applied to fingerprint-based similarity searching, yet little is known of its application to maximum common substructure (MCS)-based similarity searching. Two similarity search applications of the MCS will be focused on here. Typically, the number of bonds in the MCS, as well as the bonds in the two molecules being compared, are used in a similarity coefficient. The power of this technique can be extended using data fusion, where the MCS similarities of a set of reference molecules against one database molecule are fused. This "group fusion" technique forms the first application of the MCS in this work. The other application is that of the chemical hyperstructure. The hyperstructure concept is an alternative form of data fusion, being a hypothetical molecule that is constructed from the overlap of a set of existing molecules. This paper compares fingerprint group fusion (extended-connectivity fingerprints), MCS similarity group fusion, and hyperstructure similarity searching, and describes their relative merits and complementarity in virtual screening. It is concluded that the hyperstructure approach as implemented here is less generally effective than conventional fingerprint approaches.

  2. 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.

  3. 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.

  4. Toward Optimization of the Second Aryl Substructure Common to Transthyretin Amyloidogenesis Inhibitors Using Biochemical and Structural Studies

    PubMed Central

    Johnson, Steven M.; Connelly, Stephen; Wilson, Ian A.; Kelly, Jeffery W.

    2009-01-01

    Transthyretin (TTR) amyloidogenesis inhibitors are typically composed of two aromatic rings and a linker. We have previously established optimal structures for one aromatic ring and the linker. Herein, we employ a suboptimal linker and an optimal aryl-X substructure to rank order the desirability of aryl-Z substructures–using a library of 56 N-(3,5-dibromo-4-hydroxyphenyl)benzamides. Co-consideration of amyloid inhibition potency and ex-vivo plasma TTR binding selectivity data reveal that 2,6; 2,5; 2; 3,4,5 and 3,5 aryls bearing small substituents generate the most potent and selective inhibitors, in descending order. These benzamides generally lack undesirable thyroid hormone receptor binding and COX-1 inhibition activity. Three high-resolution TTR•inhibitor crystal structures (1.31-1.35 Å) provide insight into why these inhibitors are potent and selective, enabling future structure-based design of TTR kinetic stabilizers. PMID:19191553

  5. Maximum common substructure-based Tversky index: an asymmetric hybrid similarity measure

    NASA Astrophysics Data System (ADS)

    Kunimoto, Ryo; Vogt, Martin; Bajorath, Jürgen

    2016-07-01

    Current approaches for the assessment of molecular similarity can generally be divided into descriptor-based and substructure-based methods. The former require the application of similarity metrics that yield continuous similarity values, whereas the readout of the latter is binary (i.e. similar vs. not similar). However, it is also possible to combine descriptor-based and substructure-based methods to exploit advantages of individual methods in context and generate similarity measures for special applications. Herein we present a hybrid measure for asymmetric similarity calculations on the basis of maximum common core structures. This similarity function can be effectively applied to compare small reference compounds with larger test molecules, which is difficult using conventional metrics.

  6. Toward an improved clustering of large data sets using maximum common substructures and topological fingerprints.

    PubMed

    Böcker, Alexander

    2008-11-01

    A new clustering algorithm was developed that is able to group large data sets with more than 100,000 molecules according to their chemotypes. The algorithm preclusters a data set using a fingerprint version of the hierarchical k-means algorithm. Chemotypes are extracted from the terminal clusters via a maximum common substructure approach. Molecules forming a chemotype have to share a predefined number of rings, atoms, and non-carbon heavy atoms. In an iterative procedure, similar chemotypes and singletons are fused to larger chemotypes. Singletons that cannot be assigned to any chemotype are then grouped based on the proportion of overlap between the molecules. Representatives from each chemotype and the singletons are used in a second round of the hierarchical k-means algorithm to provide a final hierarchical grouping. Results are reported to an interactive graphical user interface which allows initial insights about the structure activity relationship (SAR) of the molecules. Example applications are shown for two chemotypes of reverse transcriptase inhibitors in the MDDR database and for the evaluation of descriptor-based similarity searching routines. A special focus was laid on the chemotype hopping potential of each individual routine. The algorithm will allow the analysis of high-throughput and virtual screening results with improved quality.

  7. A maximum common substructure-based algorithm for searching and predicting drug-like compounds.

    PubMed

    Cao, Yiqun; Jiang, Tao; Girke, Thomas

    2008-07-01

    The prediction of biologically active compounds is of great importance for high-throughput screening (HTS) approaches in drug discovery and chemical genomics. Many computational methods in this area focus on measuring the structural similarities between chemical structures. However, traditional similarity measures are often too rigid or consider only global similarities between structures. The maximum common substructure (MCS) approach provides a more promising and flexible alternative for predicting bioactive compounds. In this article, a new backtracking algorithm for MCS is proposed and compared to global similarity measurements. Our algorithm provides high flexibility in the matching process, and it is very efficient in identifying local structural similarities. To predict and cluster biologically active compounds more efficiently, the concept of basis compounds is proposed that enables researchers to easily combine the MCS-based and traditional similarity measures with modern machine learning techniques. Support vector machines (SVMs) are used to test how the MCS-based similarity measure and the basis compound vectorization method perform on two empirically tested datasets. The test results show that MCS complements the well-known atom pair descriptor-based similarity measure. By combining these two measures, our SVM-based model predicts the biological activities of chemical compounds with higher specificity and sensitivity. Supplementary data are available at Bioinformatics online.

  8. 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.

  9. Substructural controller synthesis

    NASA Technical Reports Server (NTRS)

    Su, Tzu-Jeng; Craig, Roy R., Jr.

    1989-01-01

    A decentralized design procedure which combines substructural synthesis, model reduction, decentralized controller design, subcontroller synthesis, and controller reduction is proposed for the control design of flexible structures. The structure to be controlled is decomposed into several substructures, which are modeled by component mode synthesis methods. For each substructure, a subcontroller is designed by using the linear quadratic optimal control theory. Then, a controller synthesis scheme called Substructural Controller Synthesis (SCS) is used to assemble the subcontrollers into a system controller, which is to be used to control the whole structure.

  10. 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

  11. Jet Substructure Without Trees

    SciTech Connect

    Jankowiak, Martin; Larkoski, Andrew J.; /SLAC /Stanford U., ITP

    2011-08-19

    We present an alternative approach to identifying and characterizing jet substructure. An angular correlation function is introduced that can be used to extract angular and mass scales within a jet without reference to a clustering algorithm. This procedure gives rise to a number of useful jet observables. As an application, we construct a top quark tagging algorithm that is competitive with existing methods. In preparation for the LHC, the past several years have seen extensive work on various aspects of collider searches. With the excellent resolution of the ATLAS and CMS detectors as a catalyst, one area that has undergone significant development is jet substructure physics. The use of jet substructure techniques, which probe the fine-grained details of how energy is distributed in jets, has two broad goals. First, measuring more than just the bulk properties of jets allows for additional probes of QCD. For example, jet substructure measurements can be compared against precision perturbative QCD calculations or used to tune Monte Carlo event generators. Second, jet substructure allows for additional handles in event discrimination. These handles could play an important role at the LHC in discriminating between signal and background events in a wide variety of particle searches. For example, Monte Carlo studies indicate that jet substructure techniques allow for efficient reconstruction of boosted heavy objects such as the W{sup {+-}} and Z{sup 0} gauge bosons, the top quark, and the Higgs boson.

  12. 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

  13. Finite element substructuring methods for composite mechanics

    NASA Technical Reports Server (NTRS)

    Murthy, Pappu L. N.; Chamis, Christos C.

    1988-01-01

    Finite element substructuring strategies are presented to obtain numerical solutions for three typical problems of interest to the composites community: (1) impact and toughness characterization of composites using Charpy's impact test specimen; (2) free-edge stress analysis of composite laminates; and (3) fracture toughness predictions of composites for individual and combined fracture of modes I, II, and III. The key issue common to these problems is the presence of singular or near singular stress fields. The regions prone to see steep stress gradients are substructured with progressively refined meshes to study the local response simultaneously with the global response. The results from the select examples indicate that finite element substructuring methods are computationally effective for composite singularity mechanics.

  14. 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

  15. Transients by substructuring with DMAP

    NASA Technical Reports Server (NTRS)

    Butler, T. G.

    1978-01-01

    Automated substructuring in level 16 of NASTRAN was employed as a preface to the solution of a direct transient analysis. The DMAP ALTER statements written to adapt the substructuring for transient purposes are explained. Data recovery was accomplished with transfer functions. Proof of the success of the method is presented with an application to a missile structure.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Linker-Assisted Biopolymer Aggregation

    NASA Astrophysics Data System (ADS)

    Borukhov, Itamar

    2003-03-01

    The cellular cytoskeleton relies on structural elements formed from F-actin, a highly charged, stiff biopolymer, linked together by actin-binding proteins (linkers) that can bind two actin filaments together. The resulting structures can have very different morphologies, depending on the concentrations of biopolymers and linkers. In crawling cells such as blood platelets, F-actin primarily assembles into a network but can alternatively assemble into bundles; this is important to cell motility and adhesion. This suggests that the system could be near a phase transition between networks and bundles. I will present a theoretical study that elucidates the physical mechanisms that control these structures and their stability. The study is based on a generalized Onsager theory that includes linker-mediated attractions between charged filaments, and that yields phase diagrams as a function of actin concentration and linker concentration.

  2. 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.

  3. NASTRAN multipartitioning and one-shot substructuring

    NASA Technical Reports Server (NTRS)

    Levy, A.

    1973-01-01

    For intermediate size problems where all the data is accessible, the present method of substructuring in three separate phases (for static analysis) is unneccessarily cumbersome. The versatility of NASTRAN's DMAP and internal logic lends itself to finding a practical alternative to these procedures whereby self-contained special-purpose ALTER packages can be written to be run in one pass. Two examples are presented here under the titles of multipartitioning and one-shot substructuring. The flow of multipartitioning resembles that of the present three-phase substructuring. The basic effect is to partition the structure into substructures and operate on each substructure separately. This can be used to reduce the bandwidth of a given problem as well as to store information which will allow a change to be made in one of the substructures in a later run. This latter procedure is carried out in a second program titled one-shot substructuring.

  4. 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.

  5. Substructures in hydrodynamical cluster simulations

    NASA Astrophysics Data System (ADS)

    Dolag, K.; Borgani, S.; Murante, G.; Springel, V.

    2009-10-01

    The abundance and structure of dark matter subhaloes have been analysed extensively in recent studies of dark-matter-only simulations, but comparatively little is known about the impact of baryonic physics on halo substructures. We here extend the SUBFIND algorithm for substructure identification such that it can be reliably applied to dissipative hydrodynamical simulations that include star formation. This allows, in particular, the identification of galaxies as substructures in simulations of clusters of galaxies and a determination of their content of gravitationally bound stars, dark matter and hot and cold gas. Using a large set of cosmological cluster simulations, we present a detailed analysis of halo substructures in hydrodynamical simulations of galaxy clusters, focusing in particular on the influence both of radiative and non-radiative gas physics and of non-standard physics such as thermal conduction and feedback by galactic outflows. We also examine the impact of numerical nuisance parameters such as artificial viscosity parameterizations. We find that diffuse hot gas is efficiently stripped from subhaloes when they enter the highly pressurized cluster atmosphere. This has the effect of decreasing the subhalo mass function relative to a corresponding dark-matter-only simulation. These effects are mitigated in radiative runs, where baryons condense in the central subhalo regions and form compact stellar cores. However, in all cases, only a very small fraction, of the order of one per cent, of subhaloes within the cluster virial radii preserve a gravitationally bound hot gaseous atmosphere. The fraction of mass contributed by gas in subhaloes is found to increase with the cluster-centric distance. Interestingly, this trend extends well beyond the virial radii, thus showing that galaxies feel the environment of the pressurized cluster gas over fairly large distances. The compact stellar cores (i.e. galaxies) are generally more resistant against tidal

  6. 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.

  7. 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.

  8. 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.

  9. Remote structural damage detection via substructuring

    NASA Technical Reports Server (NTRS)

    Walton, William B.; Ibanez, Paul; Yessaie, George

    1988-01-01

    An approach to structural damage detection which utilizes the concept of a substructure transfer function matrix is proposed. The major advantage of this approach is that structural changes localized within a small volume can be detected by studying the changes in the transfer function for a relatively small substructure containing the damaged portion.

  10. Siderophore-fluoroquinolone conjugates containing potential reduction-triggered linkers for drug release: synthesis and antibacterial activity.

    PubMed

    Ji, Cheng; Miller, Marvin J

    2015-06-01

    Syntheses of two Siderophore-fluoroquinolone conjugates with a potential reduction triggered linker for drug release are described. The "trimethyl lock" based linker incorporated in the conjugates was designed to be activated by taking advantage of the reductive pathway of bacterial iron metabolism. Electrochemical and LC-MS studies indicated that the linker is thermodynamically reducible by common biological reductants and the expected lactonization proceeds rapidly with concomitant release of the drug. Antibacterial activity assays revealed that conjugates with the reduction-triggered linker were more potent than their counterparts with a stable linker, which suggests that drug release occurs inside bacterial cells.

  11. 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.

  12. 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

  13. 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 .

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. Modeling Substructure in the Milky Way Galaxy

    NASA Astrophysics Data System (ADS)

    Grishaw-Jones, Claire; Thorman, P.; Iyer, T.; Guhathakurta, P.; Deep Lens Survey Collaboration

    2013-01-01

    We model substructure in the Milky Way halo using data taken from the five fields of the Deep Lens Survey (DLS). We select DLS objects that are consistent with the PSF to create color-magnitude Hess diagrams for each field. We observe significant substructure in at least two out of the five fields. To enhance the visibility of the substructure, we model and subtract the population of unresolved background galaxies, and subtract a smooth model of the Milky Way halo. This halo model is constructed by remapping the observed Hess diagram of stars in DLS Field 5 (F5), which has a smooth appearance. We use colors and absolute magnitudes from the Yonsei-Yale isochrones to create a map of distance modulus for main sequence stars in color-magnitude space for each DLS field. An Einasto model of the galaxy is used to predict the model density ratio of stars in each field as a function of distance modulus. The F5 Hess diagram is then multiplied by the model density ratio maps for F1 - F4 to yield semi-empirical model Hess diagrams. Subtracting these models from the observed Hess diagrams emphasizes the substructure of a given field. We fit simple models to the residual substructure in each DLS field using a Gaussian with three free parameters: distance of enhancement, depth along the LOS, and amplitude (i.e. strength). We discuss the use of this galaxy substructure model in calculating the overall density profile of the Milky Way.

  19. Dynamic fuzziness during linker histone action.

    PubMed

    McBryant, Steven J; Hansen, Jeffrey C

    2012-01-01

    Linker histones are multi-domain nucleosome binding proteins that stabilize higher order chromatin structures and engage in specific protein-protein interactions. Here we emphasize the structural and functional properties of the linker histone C-terminal domain (CTD), focusing on its intrinsic disorder, interaction-induced secondary structure formation and dynamic fuzziness. We argue that the fuzziness inherent in the CTD is a primary molecular mechanism underlying linker histone function in the nucleus.

  20. 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…

  1. Extracting sets of chemical substructures and protein domains governing drug-target interactions.

    PubMed

    Yamanishi, Yoshihiro; Pauwels, Edouard; Saigo, Hiroto; Stoven, Véronique

    2011-05-23

    The identification of rules governing molecular recognition between drug chemical substructures and protein functional sites is a challenging issue at many stages of the drug development process. In this paper we develop a novel method to extract sets of drug chemical substructures and protein domains that govern drug-target interactions on a genome-wide scale. This is made possible using sparse canonical correspondence analysis (SCCA) for analyzing drug substructure profiles and protein domain profiles simultaneously. The method does not depend on the availability of protein 3D structures. From a data set of known drug-target interactions including enzymes, ion channels, G protein-coupled receptors, and nuclear receptors, we extract a set of chemical substructures shared by drugs able to bind to a set of protein domains. These two sets of extracted chemical substructures and protein domains form components that can be further exploited in a drug discovery process. This approach successfully clusters protein domains that may be evolutionary unrelated but that bind a common set of chemical substructures. As shown in several examples, it can also be very helpful for predicting new protein-ligand interactions and addressing the problem of ligand specificity. The proposed method constitutes a contribution to the recent field of chemogenomics that aims to connect the chemical space with the biological space.

  2. 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

  3. 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.

  4. Solid colloids with surface-mobile linkers.

    PubMed

    van der Meulen, Stef A J; Helms, Gesa; Dogterom, Marileen

    2015-06-17

    In this report we review the possibilities of using colloids with surface mobile linkers for the study of colloidal self-assembly processes. A promising route to create systems with mobile linkers is the use of lipid (bi-)layers. These lipid layers can be either used in the form of vesicles or as coatings for hard colloids and emulsion droplets. Inside the lipid bilayers molecules can be inserted via membrane anchors. Due to the fluidity of the lipid bilayer, the anchored molecules remain mobile. The use of different lipid mixtures even allows creating Janus-like particles that exhibit directional bonding if linkers are used which have a preference for a certain lipid phase. In nature mobile linkers can be found e.g. as receptors in cells. Therefore, towards the end of the review, we also briefly address the possibility of using colloids with surface mobile linkers as model systems to mimic cell-cell interactions and cell adhesion processes.

  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. Solid colloids with surface-mobile linkers

    NASA Astrophysics Data System (ADS)

    van der Meulen, Stef A. J.; Helms, Gesa; Dogterom, Marileen

    2015-06-01

    In this report we review the possibilities of using colloids with surface mobile linkers for the study of colloidal self-assembly processes. A promising route to create systems with mobile linkers is the use of lipid (bi-)layers. These lipid layers can be either used in the form of vesicles or as coatings for hard colloids and emulsion droplets. Inside the lipid bilayers molecules can be inserted via membrane anchors. Due to the fluidity of the lipid bilayer, the anchored molecules remain mobile. The use of different lipid mixtures even allows creating Janus-like particles that exhibit directional bonding if linkers are used which have a preference for a certain lipid phase. In nature mobile linkers can be found e.g. as receptors in cells. Therefore, towards the end of the review, we also briefly address the possibility of using colloids with surface mobile linkers as model systems to mimic cell-cell interactions and cell adhesion processes.

  7. Discovering the Dark Side of CDM Substructure

    NASA Astrophysics Data System (ADS)

    Koopmans, Leon

    2012-10-01

    The existence of mass substructure is an inevitable consequence of the LCDM paradigm. Depite this clear theoretical prediction, a glaring discrepancy with the number of luminous satellites around the Milky Way {MW} has been identified, i.e. the "missing satellite problem". Notwithstanding great progress to address this problem, it remains unsolved. Moreover, the MW could be a biased environment, not representative of the typical universe. Surface brightness aberrations of gravitationally lensed images provide a complementary channel to detect substructure beyond the local Universe in mostly massive early-type galaxies. Simulations suggest a substructure mass fraction of f_sub<=1% inside the inner projected 5-10 kpc or around 5-10% inside the virial radius. Although the observed {flux-ratio/brightness} anomalies/aberrations in lenses can be explained by the presence of this mass substructure, its high rate requires a larger inferred fraction of 2-3%. To resolve these open issues convincingly, we propose to observe highly magnified Einstein rings/arcs in the ultra-violet, where the source is highly structured, to maximize sensitivity to dark substructures through surface brightness aberrations {i.e. the equivalent of the well-known flux-ratio anomalies}. Our simulations, modeling and statistical analyses show that our selected sample of 10 SLACS lens systems can pinpoint dark substructures down to 3x10^8 solar masses { 10^-4 of the ETG virial mass} and, for the first time, determine their mass fraction to down to f_sub 1%, at >99% CL. We request 30 orbits with HST WFC3-F390W to accomplish this goal.

  8. 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.

  9. Analysis of substructural variation in families of enzymatic proteins with applications to protein function prediction

    PubMed Central

    2010-01-01

    Background Structural variations caused by a wide range of physico-chemical and biological sources directly influence the function of a protein. For enzymatic proteins, the structure and chemistry of the catalytic binding site residues can be loosely defined as a substructure of the protein. Comparative analysis of drug-receptor substructures across and within species has been used for lead evaluation. Substructure-level similarity between the binding sites of functionally similar proteins has also been used to identify instances of convergent evolution among proteins. In functionally homologous protein families, shared chemistry and geometry at catalytic sites provide a common, local point of comparison among proteins that may differ significantly at the sequence, fold, or domain topology levels. Results This paper describes two key results that can be used separately or in combination for protein function analysis. The Family-wise Analysis of SubStructural Templates (FASST) method uses all-against-all substructure comparison to determine Substructural Clusters (SCs). SCs characterize the binding site substructural variation within a protein family. In this paper we focus on examples of automatically determined SCs that can be linked to phylogenetic distance between family members, segregation by conformation, and organization by homology among convergent protein lineages. The Motif Ensemble Statistical Hypothesis (MESH) framework constructs a representative motif for each protein cluster among the SCs determined by FASST to build motif ensembles that are shown through a series of function prediction experiments to improve the function prediction power of existing motifs. Conclusions FASST contributes a critical feedback and assessment step to existing binding site substructure identification methods and can be used for the thorough investigation of structure-function relationships. The application of MESH allows for an automated, statistically rigorous procedure

  10. 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.

  11. 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

  12. 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

  13. 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.

  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. 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.

  16. The gamma-ray-flux PDF from galactic halo substructure

    SciTech Connect

    Lee, Samuel K.; Ando, Shin'ichiro; Kamionkowski, Marc E-mail: ando@tapir.caltech.edu

    2009-07-01

    One of the targets of the recently launched Fermi Gamma-ray Space Telescope is a diffuse gamma-ray background from dark-matter annihilation or decay in the Galactic halo. N-body simulations and theoretical arguments suggest that the dark matter in the Galactic halo may be clumped into substructure, rather than smoothly distributed. Here we propose the gamma-ray-flux probability distribution function (PDF) as a probe of substructure in the Galactic halo. We calculate this PDF for a phenomenological model of halo substructure and determine the regions of the substructure parameter space in which the PDF may be distinguished from the PDF for a smooth distribution of dark matter. In principle, the PDF allows a statistical detection of substructure, even if individual halos cannot be detected. It may also allow detection of substructure on the smallest microhalo mass scales, ∼ M{sub ⊕}, for weakly-interacting massive particles (WIMPs). Furthermore, it may also provide a method to measure the substructure mass function. However, an analysis that assumes a typical halo substructure model and a conservative estimate of the diffuse background suggests that the substructure PDF may not be detectable in the lifespan of Fermi in the specific case that the WIMP is a neutralino. Nevertheless, for a large range of substructure, WIMP annihilation, and diffuse background models, PDF analysis may provide a clear signature of substructure.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  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. Identifying a new particle with jet substructures

    DOE PAGES

    Han, Chengcheng; Kim, Doojin; Kim, Minho; ...

    2017-01-09

    Here, 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 bene ts the identification of a Z-induced jet as a single, reconstructed object without any combinatorial ambiguity. We also find that jet substructure procedures may enhance features in some kinematic observablesmore » 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. Finally, we discuss effects from choosing different jet sizes for merged jets and jet-grooming parameters upon the MEM analyses.« less

  5. 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.

  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. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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,…

  13. 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

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

    NASA Astrophysics Data System (ADS)

    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.

  15. 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

  16. 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.

  17. 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].

  18. 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.

  19. Substructural QSAR approaches and topological pharmacophores.

    PubMed Central

    Franke, R; Huebel, S; Streich, W J

    1985-01-01

    For large and diverse data sets, simple QSAR methods based on linear and additive models can no longer be applied. In such cases topological methods using descriptors directly derivable from two-dimensional chemical structures provide a useful alternative. The results of such analyses can be used for lead optimization, to guide biological testing and even aid in the design of novel compounds. Various types of topological descriptors and algorithms are briefly discussed. Which of those is to be selected depends on the objective of the investigation and the properties of the data set. Two new methods, LOGANA and LOCON, are discussed in some more detail. With the help of these methods, substructural patterns ("topological pharmacophores") characteristic of compounds possessing a certain biological property can be evaluated. Both methods are designed in such a way that full use can be made of the data handling capacity of computers while maintaining an optimal impact of the experience of the researcher. They are model-free and do not require any mathematical knowledge. While LOGANA deals with semiquantitative or even qualitative biological data, LOCON can be applied to activity data on a continuous scale. The basic procedure in both cases consists in the stepwise combination of substructural descriptors by the logical operations "and," "or" and "not." With a simple example the utility of the methods is demonstrated. PMID:3905376

  20. 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.

  1. Lens Mapping of Dark Matter Substructure with VSOP-2

    NASA Astrophysics Data System (ADS)

    Ohashi, S.; Chiba, M.; Inoue, K. T.

    2009-08-01

    Hierarchical clustering models of cold dark matter (CDM) predict that about 5% - 10% of a galaxy-sized halo with mass ˜ 1012 solar masses (M⊙ ) resides in substructures (CDM subhalos) with masses ⪉ 108 M⊙. To directly identify such substructures, we propose to observe radio continuum emission from multiply imaged QSOs using VSOP-2 with a high angular resolution.

  2. Linker Histones Incorporation Maintains Chromatin Fiber Plasticity

    PubMed Central

    Recouvreux, Pierre; Lavelle, Christophe; Barbi, Maria; Conde e Silva, Natalia; Le Cam, Eric; Victor, Jean-Marc; Viovy, Jean-Louis

    2011-01-01

    Genomic DNA in eukaryotic cells is organized in supercoiled chromatin fibers, which undergo dynamic changes during such DNA metabolic processes as transcription or replication. Indeed, DNA-translocating enzymes like polymerases produce physical constraints in vivo. We used single-molecule micromanipulation by magnetic tweezers to study the response of chromatin to mechanical constraints in the same range as those encountered in vivo. We had previously shown that under positive torsional constraints, nucleosomes can undergo a reversible chiral transition toward a state of positive topology. We demonstrate here that chromatin fibers comprising linker histones present a torsional plasticity similar to that of naked nucleosome arrays. Chromatosomes can undergo a reversible chiral transition toward a state of positive torsion (reverse chromatosome) without loss of linker histones. PMID:21641318

  3. A Transient Response Method for Linear Coupled Substructures

    NASA Technical Reports Server (NTRS)

    Admire, J. R.; Brunty, J. A.

    1989-01-01

    A method is presented for determining the transient response of a discrete coordinate model of a linear structural system composed of substructures. The method is applicable to systems consisting of any number of substructures, both determinate and indeterminate interface boundaries, and any topological arrangement of the substructures. The method is simple to implement from a computational point of view because the equations of motion of each of the substructures are solved independently, and the interface boundary compatibility conditions are enforced at each integration time step by a matrix multiplication. The method is demonstrated for a structural system consisting of two beam segments and acted upon by a time dependent force. The numerical results from the demonstration problem validates the accuracy of the method. The application of this method to structural systems with changing interface boundary conditions between substructures is discussed.

  4. 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

  5. A photolabile linker for the solid-phase synthesis of peptide hydrazides and heterocycles.

    PubMed

    Qvortrup, Katrine; Komnatnyy, Vitaly V; Nielsen, Thomas E

    2014-09-19

    A photolabile hydrazine linker for the solid-phase synthesis of peptide hydrazides and hydrazine-derived heterocycles is presented. The developed protocols enable the efficient synthesis of structurally diverse peptide hydrazides derived from the standard amino acids, including those with side-chain protected residues at the C-terminal of the resulting peptide hydrazide, and are useful for the synthesis of dihydropyrano[2,3-c]pyrazoles. The linker is compatible with most commonly used coupling reagents and protecting groups for solid-phase peptide synthesis.

  6. 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

  7. 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.

  8. Cellular detonation - Instability and sub-structure

    NASA Astrophysics Data System (ADS)

    Sugimura, Tadayoshi; Fujiwara, Toshitaka; Lee, John H.

    The present study investigates numerically the instability and irregularity of multidimensional detonations experimentally observed over a lengthy period. By increasing computational resolution significantly, the computed results are able to reproduce most of the salient experimental features like inherent instability of a plane ZND detonation, irregular triple-shock structures seen in self-sustaining detonations, and very fine triple-shock structures superimposed in a macroscopic triple-shock configuration. Under sufficient resolution, the acquired information on the number of triple shocks, regularity and symmetry of wave structure, and detailed substructures of a triple shock configuration are found to be surprisingly incorrect. It is argued that such results would affect the future numerical simulation of detonation initiation, transition, and critical tube diameter problems where the formation of new cells is an essential mechanism.

  9. Factorization for substructures of boosted Higgs jets

    NASA Astrophysics Data System (ADS)

    Isaacson, Joshua; Li, Hsiang-nan; Li, Zhao; Yuan, C.-P.

    2017-08-01

    We present a perturbative QCD factorization formula for substructures of an energetic Higgs jet, taking the energy profile resulting from the H → b b bar decay as an example. The formula is written as a convolution of a hard Higgs decay kernel with two b-quark jet functions and a soft function that links the colors of the two b quarks. We derive an analytical expression to approximate the energy profile within a boosted Higgs jet, which significantly differs from those of ordinary QCD jets. This formalism also extends to boosted W and Z bosons in their hadronic decay modes, allowing an easy and efficient discrimination of fat jets produced from different processes.

  10. 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.

  11. Algorithms for Finding Substructure in Galaxy Clusters

    NASA Astrophysics Data System (ADS)

    Delworth, Natalie; Wilcots, Eric M.

    2017-01-01

    In order to better understand the role of environment in determining the properties of galaxies, we present statistical approaches to identifying substructure in galaxy clusters and groups. A subgroup is composed of a set of galaxies within a galaxy cluster that share similar attributes. To create subgroups from galaxies in a cluster, we explored several different clustering algorithms: Agglomerative Hierarchical Clustering, Spectral Clustering, and K-Means Clustering. We evaluate the strengths and weaknesses of these algorithms by applying them both to data from the Antlia Cluster, as well as to output from simulated galaxy clusters. We also examined how subgroups and the properties of the galaxies in those subgroups changed over time through analysis of data from simulations that extend over a long time scale. We synthesize these results to provide a perspective on how these analyses contribute to our understanding of galactic evolution.

  12. 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.

  13. Gene positional changes relative to the nuclear substructure correlate with the proliferating status of hepatocytes during liver regeneration

    PubMed Central

    Maya-Mendoza, Apolinar; Hernández-Muñoz, Rolando; Gariglio, Patricio; Aranda-Anzaldo, Armando

    2003-01-01

    In the interphase nucleus the DNA of higher eukaryotes is organised in loops anchored to a proteinaceous substructure variously named but commonly known as the nuclear matrix. Important processes of nuclear physiology, such as replication, transcription and processing of primary transcripts, occur at macromolecular complexes located at discrete sites upon the nuclear substructure. The topological relationships between gene sequences located in the DNA loops and the nuclear substructure appear to be non-random, thus posing the question of whether such relationships remain invariant or change after the critical nuclear transitions associated with cell proliferation and tissue regeneration in vivo. The hepatocytes are cells that preserve a proliferating capacity that is readily displayed after partial ablation of the liver, leading to liver regeneration in experimental animals such as the rat. Using this animal model coupled to a recently developed PCR-based method for mapping the position of specific DNA sequences relative to the nuclear substructure, we provide evidence that transient changes in the topological relationships between specific genes and the nuclear substructure occur during liver regeneration and that such changes correlate with the actual proliferating status of the cells, thus suggesting that specific transitions in the higher-order DNA structure are characteristic of the quiescent (G0) and replicating (S) phases of the cell cycle in vivo. PMID:14576303

  14. Gene positional changes relative to the nuclear substructure correlate with the proliferating status of hepatocytes during liver regeneration.

    PubMed

    Maya-Mendoza, Apolinar; Hernández-Muñoz, Rolando; Gariglio, Patricio; Aranda-Anzaldo, Armando

    2003-11-01

    In the interphase nucleus the DNA of higher eukaryotes is organised in loops anchored to a proteinaceous substructure variously named but commonly known as the nuclear matrix. Important processes of nuclear physiology, such as replication, transcription and processing of primary transcripts, occur at macromolecular complexes located at discrete sites upon the nuclear substructure. The topological relationships between gene sequences located in the DNA loops and the nuclear substructure appear to be non-random, thus posing the question of whether such relationships remain invariant or change after the critical nuclear transitions associated with cell proliferation and tissue regeneration in vivo. The hepatocytes are cells that preserve a proliferating capacity that is readily displayed after partial ablation of the liver, leading to liver regeneration in experimental animals such as the rat. Using this animal model coupled to a recently developed PCR-based method for mapping the position of specific DNA sequences relative to the nuclear substructure, we provide evidence that transient changes in the topological relationships between specific genes and the nuclear substructure occur during liver regeneration and that such changes correlate with the actual proliferating status of the cells, thus suggesting that specific transitions in the higher-order DNA structure are characteristic of the quiescent (G0) and replicating (S) phases of the cell cycle in vivo.

  15. 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

  16. 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.

  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. 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.

  19. 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.

  20. 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.

  1. 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.

  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. 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.

  5. 3. VIEW OF SOUTH FACE AND CONSTRUCTION DETAIL OF SUBSTRUCTURE ...

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

    3. VIEW OF SOUTH FACE AND CONSTRUCTION DETAIL OF SUBSTRUCTURE FROM NORTH BANK. RETAINING WALL OF GAUGING STATION IS VISIBLE IN BACKGROUND UNDER BRIDGE. - Old Happy Isles Bridge, Spanning Merced River on service road, Yosemite Village, Mariposa County, CA

  6. 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

  7. 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

  8. 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

  9. 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.

  10. Copy of "Plan of the Substructure of Center Street Bridge, ...

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

    Copy of "Plan of the Substructure of Center Street Bridge, Cleveland (October 1898)." Drawing courtesy Engineering Dept., City of Cleveland - Center Street Swing Bridge, Southwest of Public Square, Cleveland, Cuyahoga County, OH

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. Using Network Methodology to Infer Population Substructure

    PubMed Central

    Prokopenko, Dmitry; Hecker, Julian; Silverman, Edwin; Nöthen, Markus M.; Schmid, Matthias; Lange, Christoph; Loehlein Fier, Heide

    2015-01-01

    One of the main caveats of association studies is the possible affection by bias due to population stratification. Existing methods rely on model-based approaches like structure and ADMIXTURE or on principal component analysis like EIGENSTRAT. Here we provide a novel visualization technique and describe the problem of population substructure from a graph-theoretical point of view. We group the sequenced individuals into triads, which depict the relational structure, on the basis of a predefined pairwise similarity measure. We then merge the triads into a network and apply community detection algorithms in order to identify homogeneous subgroups or communities, which can further be incorporated as covariates into logistic regression. We apply our method to populations from different continents in the 1000 Genomes Project and evaluate the type 1 error based on the empirical p-values. The application to 1000 Genomes data suggests that the network approach provides a very fine resolution of the underlying ancestral population structure. Besides we show in simulations, that in the presence of discrete population structures, our developed approach maintains the type 1 error more precisely than existing approaches. PMID:26098940

  16. 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.

  17. 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.

  18. Acetophenone-based linker for solid-phase peptide synthesis.

    PubMed

    Bui, C T; Bray, A M; Nguyen, T; Ercole, F; Rasoul, F; Sampson, W; Maeji, N J

    2000-02-01

    A new and cost-effective linker for the generation of carboxylic acid end groups on Multipin supports (SynPhase crowns) has been developed. Synthesis of the linker was based on modification of grafted polystyrene (PS) crowns to generate a hydroxyethyl moiety which is acid labile in 10-20% trifluoroacetic acid (TFA) in dichloromethane (DCM). Solid-phase syntheses of model decapeptides using this linker are described.

  19. Non–T Cell Activation Linker (NTAL)

    PubMed Central

    Brdička, Tomáš; Imrich, Martin; Angelisová, Pavla; Brdičková, Naděžda; Horváth, Ondrej; Špička, Jiří; Hilgert, Ivan; Lusková, Petra; Dráber, Petr; Novák, Petr; Engels, Niklas; Wienands, Jürgen; Simeoni, Luca; Österreicher, Jan; Aguado, Enrique; Malissen, Marie; Schraven, Burkhart; Hořejší, Václav

    2002-01-01

    A key molecule necessary for activation of T lymphocytes through their antigen-specific T cell receptor (TCR) is the transmembrane adaptor protein LAT (linker for activation of T cells). Upon TCR engagement, LAT becomes rapidly tyrosine phosphorylated and then serves as a scaffold organizing a multicomponent complex that is indispensable for induction of further downstream steps of the signaling cascade. Here we describe the identification and preliminary characterization of a novel transmembrane adaptor protein that is structurally and evolutionarily related to LAT and is expressed in B lymphocytes, natural killer (NK) cells, monocytes, and mast cells but not in resting T lymphocytes. This novel transmembrane adaptor protein, termed NTAL (non–T cell activation linker) is the product of a previously identified WBSCR5 gene of so far unknown function. NTAL becomes rapidly tyrosine-phosphorylated upon cross-linking of the B cell receptor (BCR) or of high-affinity Fcγ- and Fcɛ-receptors of myeloid cells and then associates with the cytoplasmic signaling molecules Grb2, Sos1, Gab1, and c-Cbl. NTAL expressed in the LAT-deficient T cell line J.CaM2.5 becomes tyrosine phosphorylated and rescues activation of Erk1/2 and minimal transient elevation of cytoplasmic calcium level upon TCR/CD3 cross-linking. Thus, NTAL appears to be a structural and possibly also functional homologue of LAT in non–T cells. PMID:12486104

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. A Simple and Effective Cleavable Linker for Chemical Proteomics Applications*

    PubMed Central

    Yang, Yinliang; Hahne, Hannes; Kuster, Bernhard; Verhelst, Steven H. L.

    2013-01-01

    The study of metabolically labeled or probe-modified proteins is an important area in chemical proteomics. Isolation and purification of the protein targets is a necessary step before MS identification. The biotin-streptavidin system is widely used in this process, but the harsh denaturing conditions also release natively biotinylated proteins and non-selectively bound proteins. A cleavable linker strategy is a promising approach for solving this problem. Though several cleavable linkers have been developed and tested, an efficient, easily synthesized, and inexpensive cleavable linker is a desirable addition to the proteomics toolbox. Here, we describe the chemical proteomics application of a vicinal diol cleavable linker. Through easy-to-handle chemistry we incorporate this linker into an activity-based probe and a biotin alkyne tag amenable for bioorthogonal ligation. With these reagents, background protein identifications are significantly reduced relative to standard on-bead digestion. PMID:23028061

  11. A Helix-Stabilizing Linker Improves Subcutaneous Bioavailability of a Helical Peptide Independent of Linker Lipophilicity

    PubMed Central

    Zhang, Liang; Navaratna, Tejas; Thurber, Greg M.

    2016-01-01

    Stabilized peptides address several limitations to peptide-based imaging agents and therapeutics such as poor stability and low affinity due to conformational flexibility. There is also active research in developing these compounds for intracellular drug targeting, and significant efforts have been invested to determine the effects of helix stabilization on intracellular delivery. However, much less is known about the impact on other pharmacokinetic parameters such as plasma clearance and bioavailability. We investigated the effect of different fluorescent helix-stabilizing linkers with varying lipophilicity on subcutaneous (SC) bioavailability using the glucagon-like peptide-1 (GLP-1) receptor ligand exendin as a model system. The stabilized peptides showed significantly higher protease resistance and increased bioavailability independent of linker hydrophilicity, and all subcutaneously delivered conjugates were able to successfully target the islets of Langerhans with high specificity. The lipophilic peptide variants had slower absorption and plasma clearance than their respective hydrophilic conjugates, and the absolute bioavailability was also lower likely due to the longer residence times in the skin. The ease and efficiency of double-click helix stabilization chemistries is a useful tool for increasing the bioavailability of peptide therapeutics, many of which suffer from rapid in vivo protease degradation. Helix stabilization using linkers of varying lipophilicity can further control SC absorption and clearance rates to customize plasma pharmacokinetics. PMID:27327034

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. System for detecting substructure microfractures and method therefore

    NASA Technical Reports Server (NTRS)

    Parthasarathy, S. P.; Narasimhan, K. Y. (Inventor)

    1979-01-01

    Bursts of signals at different frequencies are induced into substructure, adjacent to a borehole. The return signals from each burst of signals are normalized to compensate for the attenuation, experienced by more distant return signals. The peak amplitudes of return signals, above a selected level, are cut off, and an average signal is produced from the normalized amplitude-limited return signals of each burst. The averaged signals of the return signals of all the signal bursts at the different frequencies are processed to provide a combined signal, whose amplitude is related to the microfracture density of the substructure adjacent to the borehole.

  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. Pyrene intercalating nucleic acids with a carbon linker.

    PubMed

    Østergaard, Michael E; Wamberg, Michael C; Pedersen, Erik B

    2011-03-01

    We have synthesized a carbon linker analogue of INA (oligonucleotides containing insertions of 1-O-(1-pyrenylmethyl)glycerol). Thermal stability studies showed an increase in melting temperature in favor of the carbon linker analogue. We also synthesized a carbon linker analogue with two pyrenes geminally attached. Fluorescence studies of this intercalating nucleic acid with the pyrene moieties inserted as a bulge showed formation of an excimer band. When a mismatch was introduced at the site of the intercalator, an excimer band was formed for the destabilized duplexes whereas an exciplex band was observed when the stability of the duplex was retained.

  5. Correlation among DNA Linker Length, Linker Histone Concentration, and Histone Tails in Chromatin.

    PubMed

    Luque, Antoni; Ozer, Gungor; Schlick, Tamar

    2016-06-07

    Eukaryotic cells condense their genetic material in the nucleus in the form of chromatin, a macromolecular complex made of DNA and multiple proteins. The structure of chromatin is intimately connected to the regulation of all eukaryotic organisms, from amoebas to humans, but its organization remains largely unknown. The nucleosome repeat length (NRL) and the concentration of linker histones (ρLH) are two structural parameters that vary among cell types and cell cycles; the NRL is the number of DNA basepairs wound around each nucleosome core plus the number of basepairs linking successive nucleosomes. Recent studies have found a linear empirical relationship between the variation of these two properties for different cells, but its underlying mechanism remains elusive. Here we apply our established mesoscale chromatin model to explore the mechanisms responsible for this relationship, by investigating chromatin fibers as a function of NRL and ρLH combinations. We find that a threshold of linker histone concentration triggers the compaction of chromatin into well-formed 30-nm fibers; this critical value increases linearly with NRL, except for long NRLs, where the fibers remain disorganized. Remarkably, the interaction patterns between core histone tails and chromatin elements are highly sensitive to the NRL and ρLH combination, suggesting a molecular mechanism that could have a key role in regulating the structural state of the fibers in the cell. An estimate of the minimized work and volume associated with storage of chromatin fibers in the nucleus further suggests factors that could spontaneously regulate the NRL as a function of linker histone concentration. Both the tail interaction map and DNA packing considerations support the empirical NRL/ρLH relationship and offer a framework to interpret experiments for different chromatin conditions in the cell. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  6. A rod-linker-contained R-phycoerythrin complex from the intact phycobilisome of the marine red alga Polysiphonia urceolata.

    PubMed

    Sun, Li; Wang, Shumei; Gong, Xieqin; Chen, Lixue

    2004-10-25

    A linker-contained R-phycoerythrin (R-PE) complex was obtained by the Sephadex G-150 column chromatography from the Polysiphonia urceolata phycobilisome (PBS) that was dis-associated at 37 degrees C for 6 h in the dilute phosphate buffer (pH 7.0) with 5% (m/v) sodium dodecyl sulfate (SDS). The R-PE complex showed three absorption peaks at 498, 538 and 567 nm, and a fluorescence emission maximum at 578 nm. Polypeptide analysis of the complex by the 8-25% (m/v) gradient SDS-polyacrylamide gel electrophoresis demonstrated that it contained three red subunits, alpha(PE)(17.6),beta(PE)(19.2) and gamma(PE)(31.0), and a colorless 35.3 kDa rod-linker L(R)(35.3). Polypeptide proportion of the complex demonstrated that it was a hexamer in aggregate form gamma(PE)(31.6), (alpha(PE)(17.6),beta(PE)(19.2))(3)L(R)(35.3)(alpha(PE)(17.6),beta(PE)(19.2)(3)gamma(PE)(31.6) which is proposed to originate from a rod assembly of hexamer-linker-hexamer the substructure alpha(PE)(17.6),beta(PE)(19.2)(3) of which was decomposed off from the ends of the assembly during the PBS dissociation. The distinctive stability of the prepared hexamer is attributed to a large extent to the electrostatic interaction among its polypeptides, but not to the hydrophobic interaction.

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

    PubMed

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

    2016-12-12

    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 Ni(2+). The Ni(2+) ion was found to be complexed between two CRDs via crystal packing contacts. The coordination between Ni(2+) 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.

  8. 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

  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. Novel SHM method to locate damages in substructures based on VARX models

    NASA Astrophysics Data System (ADS)

    Ugalde, U.; Anduaga, J.; Martínez, F.; Iturrospe, A.

    2015-07-01

    A novel damage localization method is proposed, which is based on a substructuring approach and makes use of Vector Auto-Regressive with eXogenous input (VARX) models. The substructuring approach aims to divide the monitored structure into several multi-DOF isolated substructures. Later, each individual substructure is modelled as a VARX model, and the health of each substructure is determined analyzing the variation of the VARX model. The method allows to detect whether the isolated substructure is damaged, and besides allows to locate and quantify the damage within the substructure. It is not necessary to have a theoretical model of the structure and only the measured displacement data is required to estimate the isolated substructure's VARX model. The proposed method is validated by simulations of a two-dimensional lattice structure.

  11. 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.

  12. 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.

  13. Abell 2744: too much substructure for ΛCDM?

    NASA Astrophysics Data System (ADS)

    Schwinn, J.; Jauzac, M.; Baugh, C. M.; Bartelmann, M.; Eckert, D.; Harvey, D.; Natarajan, P.; Massey, R.

    2017-05-01

    The massive substructures found in Abell 2744 by Jauzac et al. present a challenge to the cold dark matter paradigm due to their number and proximity to the cluster centre. We use one of the biggest N-body simulations, the Millennium XXL, to investigate the substructure in a large sample of massive dark matter haloes. A range of effects that influence the comparison with the observations is considered, extending the preliminary evaluation carried out by Jauzac et al. There are many tens of haloes in the simulation with a total mass comparable with or larger than that of Abell 2744. However, we find no haloes with a number and distribution of massive substructures (>5 × 1013 M⊙) that is close to that inferred from the observations of Abell 2744. The application of extreme value statistics suggests that we would need a simulation of at least 10 times the volume of the Millennium XXL to find a single dark matter halo with a similar internal structure to Abell 2744. Explaining the distribution of massive substructures in clusters is a new hurdle for hierarchical models to negotiate, which is not weakened by appeals to baryonic physics or uncertainty over the nature of the dark matter particle.

  14. 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…

  15. 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.

  16. 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.

  17. QUANTIFYING KINEMATIC SUBSTRUCTURE IN THE MILKY WAY'S STELLAR HALO

    SciTech Connect

    Xue Xiangxiang; Zhao Gang; Luo Ali; Rix, Hans-Walter; Bell, Eric F.; Koposov, Sergey E.; Kang, Xi; Liu, Chao; Yanny, Brian; Beers, Timothy C.; Lee, Young Sun; Bullock, James S.; Johnston, Kathryn V.; Morrison, Heather; Rockosi, Constance

    2011-09-01

    We present and analyze the positions, distances, and radial velocities for over 4000 blue horizontal-branch (BHB) stars in the Milky Way's halo, drawn from SDSS DR8. We search for position-velocity substructure in these data, a signature of the hierarchical assembly of the stellar halo. Using a cumulative 'close pair distribution' as a statistic in the four-dimensional space of sky position, distance, and velocity, we quantify the presence of position-velocity substructure at high statistical significance among the BHB stars: pairs of BHB stars that are close in position on the sky tend to have more similar distances and radial velocities compared to a random sampling of these overall distributions. We make analogous mock observations of 11 numerical halo formation simulations, in which the stellar halo is entirely composed of disrupted satellite debris, and find a level of substructure comparable to that seen in the actually observed BHB star sample. This result quantitatively confirms the hierarchical build-up of the stellar halo through a signature in phase (position-velocity) space. In detail, the structure present in the BHB stars is somewhat less prominent than that seen in most simulated halos, quite possibly because BHB stars represent an older sub-population. BHB stars located beyond 20 kpc from the Galactic center exhibit stronger substructure than at r{sub gc} < 20 kpc.

  18. 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…

  19. 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.

  20. 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.

  1. 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.

  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. Evaluation of a timber column bent substructure after more than 60 years in-service

    Treesearch

    James P. Wacker; Xiping Wang; Douglas R. Rammer; William J. Nelson

    2011-01-01

    This paper describes both the field evaluation and laboratory testing of two timber-column-bent bridge substructures. These substructures served as intermediate pier supports for the East Deer Park Drive Bridge located in Gaithersburg, Maryland. A field evaluation of the bridge substructure was conducted in September 2008. Nondestructive testing was performed with a...

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. Contribution of linker stability to the activities of anticancer immunoconjugates.

    PubMed

    Alley, Stephen C; Benjamin, Dennis R; Jeffrey, Scott C; Okeley, Nicole M; Meyer, Damon L; Sanderson, Russell J; Senter, Peter D

    2008-03-01

    The linker component of antibody-drug conjugates (ADC) is a key feature in developing optimized therapeutic agents that are highly active at well tolerated doses. For maximal intratumoral drug delivery, linkers are required that are highly stable in the systemic circulation, yet allow for efficient drug release at the target site. In this respect, amide bond-based technologies constitute a technological advancement, since the linker half-lives in circulation ( t 1/2 approximately 7 days) are much longer than earlier generation linkers that break down within 1-2 days. The amide linkers, some of which contain peptides, are appended to the mAb carriers through thioether/maleimide adducts. Here, we describe that use of a bromoacetamidecaproyl (bac) in place of the maleimidocaproyl (mc) increases the plasma stability of resulting thioether ADCs. One such ADC, 1F6-C4v2-bac-MMAF, which is directed against the CD70 antigen on lymphomas and renal cell carcinoma, was prepared containing a bac thioether spacer between the drug (MMAF) and the mAb carrier (1F6-C4v2). There was no measurable systemic drug release from this ADC for 2 weeks postadministration in mice. In order to assess the impact of improving linker stability beyond mc containing ADCs, a series of mc and bac-linked 1F6-MMAF conjugates were compared for tolerability, intratumoral drug delivery, and therapeutic efficacy in nude mice with renal cell carcinoma xenografts. There were no statistically significant efficacy differences between sets of mc and bac containing ADCs, although the bac linker technology led to 25% higher intratumoral drug exposure over a 7 day period compared to the corresponding mc linker. The mechanism of drug release from maleimide-adducts likely involves a retro-Michael reaction that takes place in plasma, based on in vitro studies demonstrating that some of the released drug-maleimide derivative became covalently bound to cysteine-34 of serum albumin. In summary, the data indicate that new

  12. Inter-domain linker prediction using amino acid compositional index.

    PubMed

    Shatnawi, Maad; Zaki, Nazar

    2015-04-01

    Protein chains are generally long and consist of multiple domains. Domains are distinct structural units of a protein that can evolve and function independently. The accurate and reliable prediction of protein domain linkers and boundaries is often considered to be the initial step of protein tertiary structure and function predictions. In this paper, we introduce CISA as a method for predicting inter-domain linker regions solely from the amino acid sequence information. The method first computes the amino acid compositional index from the protein sequence dataset of domain-linker segments and the amino acid composition. A preference profile is then generated by calculating the average compositional index values along the amino acid sequence using a sliding window. Finally, the protein sequence is segmented into intervals and a simulated annealing algorithm is employed to enhance the prediction by finding the optimal threshold value for each segment that separates domains from inter-domain linkers. The method was tested on two standard protein datasets and showed considerable improvement over the state-of-the-art domain linker prediction methods. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. 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.

  14. 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

  15. 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.

  16. SUBSTRUCTURE IN THE STELLAR HALOS OF THE AQUARIUS SIMULATIONS

    SciTech Connect

    Helmi, Amina; Cooper, A. P.; Cole, S.; Frenk, C. S.; White, S. D. M.; Navarro, J. F.

    2011-05-20

    We characterize the substructure in the simulated stellar halos of Cooper et al. which were formed by the disruption of satellite galaxies within the cosmological N-body simulations of galactic halos of the Aquarius project. These stellar halos exhibit a wealth of tidal features: broad overdensities and very narrow faint streams akin to those observed around the Milky Way. The substructures are distributed anisotropically on the sky, a characteristic that should become apparent in the next generation of photometric surveys. The normalized RMS of the density of stars on the sky appears to be systematically larger for our halos compared with the value estimated for the Milky Way from main-sequence turnoff stars in the Sloan Digital Sky Survey. We show that this is likely to be due in part to contamination by faint QSOs and redder main-sequence stars, and might suggest that {approx}10% of the Milky Way halo stars have formed in situ.

  17. Observations of Cluster Substructure using Weakly Lensed Sextupole Moments

    SciTech Connect

    Irwin, John

    2003-08-01

    Since dark matter clusters and groups may have substructure, we have examined the sextupole content of Hubble images looking for a curvature signature in background galaxies that would arise from galaxy-galaxy lensing. We describe techniques for extracting and analyzing sextupole and higher weakly lensed moments. Indications of substructure, via spatial clumping of curved background galaxies, were observed in the image of CL0024 and then surprisingly in both Hubble deep fields. We estimate the dark cluster masses in the deep field. Alternatives to a lensing hypothesis appear improbable, but better statistics will be required to exclude them conclusively. Observation of sextupole moments would then provide a means to measure dark matter structure on smaller length scales than heretofore.

  18. 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

  19. Searches for Exotic Physics in ATLAS using Substructure Techniques

    NASA Astrophysics Data System (ADS)

    Behr, J. Katharina; ATLAS Collaboration

    2017-07-01

    The significant increase of the centre-of-mass energy of the Large Hadron Collider (LHC) from 8 to 13 TeV has allowed the LHC experiments to explore previously inaccessible kinematic regimes in their search for phenomena beyond the Standard Model. The sensitivity of these searches depends crucially on the efficient reconstruction and identification of hadronic decays of highly energetic (boosted) objects, the decay products of which are typically collimated into a single large jet with a characteristic substructure. In this contribution, the searches conducted by the ATLAS experiment on data recorded during 2015 and 2016 that rely on jet substructure techniques to identify signatures of interest are reviewed. A particular emphasis is placed on recent developments in the rapidly evolving field of boosted object tagging.

  20. 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.

  1. 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.

  2. 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.

  3. Development of an expert system for the simulation model for casting metal substructure of a metal-ceramic crown design.

    PubMed

    Matin, Ivan; Hadzistevic, Miodrag; Vukelic, Djordje; Potran, Michal; Brajlih, Tomaz

    2017-07-01

    Nowadays, the integrated CAD/CAE systems are favored solutions for the design of simulation models for casting metal substructures of metal-ceramic crowns. The worldwide authors have used different approaches to solve the problems using an expert system. Despite substantial research progress in the design of experts systems for the simulation model design and manufacturing have insufficiently considered the specifics of casting in dentistry, especially the need for further CAD, RE, CAE for the estimation of casting parameters and the control of the casting machine. The novel expert system performs the following: CAD modeling of the simulation model for casting, fast modeling of gate design, CAD eligibility and cast ability check of the model, estimation and running of the program code for the casting machine, as well as manufacturing time reduction of the metal substructure. The authors propose an integration method using common data model approach, blackboard architecture, rule-based reasoning and iterative redesign method. Arithmetic mean roughness values was determinated with constant Gauss low-pass filter (cut-off length of 2.5mm) according to ISO 4287 using Mahr MARSURF PS1. Dimensional deviation between the designed model and manufactured cast was determined using the coordinate measuring machine Zeiss Contura G2 and GOM Inspect software. The ES allows for obtaining the castings derived roughness grade number N7. The dimensional deviation between the simulation model of the metal substructure and the manufactured cast is 0.018mm. The arithmetic mean roughness values measured on the casting substructure are from 1.935µm to 2.778µm. The realized developed expert system with the integrated database is fully applicable for the observed hardware and software. Values of the arithmetic mean roughness and dimensional deviation indicate that casting substructures are surface quality, which is more than enough and useful for direct porcelain veneering. The

  4. 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

  5. The automated multi-stage substructuring system for NASTRAN

    NASA Technical Reports Server (NTRS)

    Field, E. I.; Herting, D. N.; Herendeen, D. L.; Hoesly, R. L.

    1975-01-01

    The substructuring capability developed for eventual installation in Level 16 is now operational in a test version of NASTRAN. Its features are summarized. These include the user-oriented, Case Control type control language, the automated multi-stage matrix processing, the independent direct access data storage facilities, and the static and normal modes solution capabilities. A complete problem analysis sequence is presented with card-by-card description of the user input.

  6. Stellar Substructures Around the Hercules Dwarf Spheroidal Galaxy

    NASA Astrophysics Data System (ADS)

    Roderick, T. A.; Jerjen, H.; Mackey, A. D.; Da Costa, G. S.

    2015-05-01

    We present deep g and i band Dark Energy Camera stellar photometry of the Hercules Milky Way satellite galaxy, and its surrounding field, out to a radial distance of 5.4 times the tidal radius. We have identified nine extended stellar substructures associated with the dwarf; preferentially distributed along the major axis of the galaxy. Two significant over-densities lie outside the 95% confidence band for the likely orbital path of the galaxy and appear to be free-floating tidal debris. We estimate the luminosity of the new stellar substructures, and find that approximately the same amount of stellar flux is lying in these extended structures as inside the main body of Hercules. We also analyze the distribution of candidate blue-horizontal-branch stars and find agreement with the alignment of the substructures at a confidence level greater than 98%. Our analysis provides a quantitative demonstration that Hercules is a strongly tidally disrupted system, with noticeable stellar features at least 1.9 kpc away from the galaxy.

  7. 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.

  8. 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

  9. Replacement of unobservable coupling DoFs in substructure decoupling

    NASA Astrophysics Data System (ADS)

    D'Ambrogio, Walter; Fregolent, Annalisa

    2017-10-01

    In this paper, suitable criteria are sought for an optimal replacement of unobservable coupling DoFs when performing substructure decoupling, that is the identification of a dynamic model of a substructure embedded in a known structure. The need arises since coupling DoFs are often difficult to observe, either because they cannot be easily accessed or because they include rotational DoFs. The substitution must be carried out both to preserve the information that would be lost when some coupling DoFs are not taken into account, and to avoid or minimize ill-conditioning problems. As shown in previous papers, coupling DoFs can be effectively replaced by internal DoFs for the sake of substructure decoupling. Furthermore, criteria for an appropriate selection of the internal DoFs used to replace unobservable coupling DoFs are sketched, which involve either the Frequency Response Function (FRF) or the transmissibility between internal and coupling DoFs. Here, previously introduced FRF and transmissibility criteria are combined with the condition number of the interface flexibility matrix to develop a procedure to optimally replace some coupling DoFs with a subset of internal DoFs. The procedure is tested using both simulated and experimental data of a tree structure (known structure), made by a cantilever beam with two offset short arms, coupled to another beam (structure to be identified).

  10. Squalene-derived Flexible Linkers for Bioactive Peptides†

    PubMed Central

    Jagadish, Bhumasamudram; Sankaranarayanan, Rajesh; Xu, Liping; Richards, Reyniak; Vagner, Josef; Hruby, Victor J.; Gillies, Robert J.; Mash*, Eugene A.

    2007-01-01

    A regiochemical and stereochemical mixture of flexible linkers bearing terminal azide functionality was synthesized in two steps from squalene and was used to connect two high affinity NDP-α-MSH ligands or two low affinity MSH(4) ligands. The ligands were N-terminally acylated using N-hydroxysuccinimidoyl 5-hexynoate and were subsequently attached to the linker via copper-catalyzed “click” 3+2 cyclization of the azide and alkyne moieties. In vitro biological evaluations showed that the binding affinity to the human melanocortin 4 receptor was not diminished for most linker-ligand combinations relative to the corresponding parental ligand. Statistical and cooperative binding effects were observed for dimeric constructs containing the low affinity ligand MSH(4), but not for dimeric NDP-α-MSH constructs, presumably due to slow off rates for this high affinity ligand. PMID:17448660

  11. Bioinformatics in crosslinking chemistry of collagen with selective cross linkers

    PubMed Central

    2011-01-01

    Background Identifying the molecular interactions using bioinformatics tools before venturing into wet lab studies saves the energy and time considerably. The present study summarizes, molecular interactions and binding energy calculations made for major structural protein, collagen of Type I and Type III with the chosen cross-linkers, namely, coenzyme Q10, dopaquinone, embelin, embelin complex-1 & 2, idebenone, 5-O-methyl embelin, potassium embelate and vilangin. Results Molecular descriptive analyses suggest, dopaquinone, embelin, idebenone, 5-O-methyl embelin, and potassium embelate display nil violations. And results of docking analyses revealed, best affinity for Type I (- 4.74 kcal/mol) and type III (-4.94 kcal/mol) collagen was with dopaquinone. Conclusions Among the selected cross-linkers, dopaquinone, embelin, potassium embelate and 5-O-methyl embelin were the suitable cross-linkers for both Type I and Type III collagen and stabilizes the collagen at the expected level. PMID:21989371

  12. 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.

  13. 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.

  14. 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

  15. Immune Response Modulation of Conjugated Agonists with Changing Linker Length.

    PubMed

    Ryu, Keun Ah; Slowinska, Katarzyna; Moore, Troy; Esser-Kahn, Aaron

    2016-12-16

    We report immune response modulation with linked Toll-like receptor (TLR) agonists. Conjugating two agonists of synergistic TLRs induce an increase in immune activity compared to equal molarity of soluble agonists. Additionally, varying the distance between the agonists by changing the linker length alters the level of macrophage NF-κB activity as well as primary bone marrow derived dendritic cell IL-6 production. This modulation is effected by the size of the agonists and the pairing of the stimulated TLRs. The sensitivity of linker-length-dependent immune activity of conjugated agonists provides the potential for developing application specific therapeutics.

  16. 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).

  17. 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.

  18. GLAST And Dark Matter Substructure in the Milky Way

    SciTech Connect

    Kuhlen, Michael; Diemand, Jurg; Madau, Piero; /UC, Santa Cruz, Astron. Astrophys. /Garching, Max Planck Inst.

    2011-11-29

    We discuss the possibility of GLAST detecting gamma-rays from the annihilation of neutralino dark matter in the Galactic halo. We have used 'Via Lactea', currently the highest resolution simulation of cold dark matter substructure, to quantify the contribution of subhalos to the annihilation signal. We present a simulated allsky map of the expected gamma-ray counts from dark matter annihilation, assuming standard values of particle mass and cross section. In this case GLAST should be able to detect the Galactic center and several individual subhalos. One of the most exciting discoveries that the Gamma-ray Large Area Space Telescope (GLAST) could make, is the detection of gamma-rays from the annihilation of dark matter (DM). Such a measurement would directly address one of the major physics problems of our time: the nature of the DM particle. Whether or not GLAST will actually detect a DM annihilation signal depends on both unknown particle physics and unknown astrophysics theory. Particle physics uncertainties include the type of particle (axion, neutralino, Kaluza-Klein particle, etc.), its mass, and its interaction cross section. From the astrophysical side it appears that DM is not smoothly distributed throughout the Galaxy halo, but instead exhibits abundant clumpy substructure, in the form of thousands of so-called subhalos. The observability of DM annihilation radiation originating in Galactic DM subhalos depends on their abundance, distribution, and internal properties. Numerical simulations have been used in the past to estimate the annihilation flux from DM substructure, but since the subhalo properties, especially their central density profile, which determines their annihilation luminosity, are very sensitive to numerical resolution, it makes sense to re-examine their contribution with higher resolution simulations.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. Shaken and stirred: the Milky Way's dark substructures

    NASA Astrophysics Data System (ADS)

    Sawala, Till; Pihajoki, Pauli; Johansson, Peter H.; Frenk, Carlos S.; Navarro, Julio F.; Oman, Kyle A.; White, Simon D. M.

    2017-06-01

    The predicted abundance and properties of the low-mass substructures embedded inside larger dark matter haloes differ sharply among alternative dark matter models. Too small to host galaxies themselves, these subhaloes may still be detected via gravitational lensing or via perturbations of the Milky Way's globular cluster streams and its stellar disc. Here, we use the Apostle cosmological simulations to predict the abundance and the spatial and velocity distributions of subhaloes in the range 106.5-108.5 M⊙ inside haloes of mass ˜1012 M⊙ in Λ cold dark matter. Although these subhaloes are themselves devoid of baryons, we find that baryonic effects are important. Compared to corresponding dark matter only simulations, the loss of baryons from subhaloes and stronger tidal disruption due to the presence of baryons near the centre of the main halo reduce the number of subhaloes by ˜1/4 to 1/2, independently of subhalo mass, but increasingly towards the host halo centre. We also find that subhaloes have non-Maxwellian orbital velocity distributions, with centrally rising velocity anisotropy and positive velocity bias that reduces the number of low-velocity subhaloes, particularly near the halo centre. We parametrize the predicted population of subhaloes in terms of mass, galactocentric distance and velocities. We discuss implications of our results for the prospects of detecting dark matter substructures and for possible inferences about the nature of dark matter.

  11. 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.

  12. 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

  13. Isolation and analysis of linker histones across cellular compartments

    PubMed Central

    Harshman, Sean W.; Chen, Michael M.; Branson, Owen E.; Jacob, Naduparambil K.; Johnson, Amy J.; Byrd, John C.; Freitas, Michael A.

    2013-01-01

    Analysis of histones, especially histone H1, is severely limited by immunological reagent availability. This paper describes the application of cellular fractionation with LC-MS for profiling histones in the cytosol and upon chromatin. First, we show that linker histones enriched by cellular fractionation gives less nuclear contamination and higher histone content than when prepared by nuclei isolation. Second, we profiled the soluble linker histones throughout the cell cycle revealing phosphorylation increases as cells reach mitosis. Finally, we monitored histone H1.2–H1.5 translocation to the cytosol in response to the CDK inhibitor flavopiridol in primary CLL cells treated ex vivo. Data shows all H1 variants translocate in response to drug treatment with no specific order to their cytosolic appearance. The results illustrate the utility of cellular fractionation in conjunction with LC-MS for the analysis of histone H1 throughout the cell. PMID:24013129

  14. 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.

  15. 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.

  16. Actin cross-linkers and the shape of stereocilia.

    PubMed

    Lenz, Martin; Prost, Jacques; Joanny, Jean-François

    2010-10-20

    Stereocilia are actin-based cellular protrusions essential for hearing. We propose that they are shaped by the detachment dynamics of actin cross-linkers, in particular espin. We account for experimentally observed stereocilium shapes, treadmilling velocity to length relationship, espin 1 localization profile, and microvillus length to espin level relationship. If the cross-linkers are allowed to reattach, our model yields a dynamical phase transition toward unbounded growth. Considering the simplified case of a noninteracting, one-filament system, we calculate the length probability distribution in the growing phase and its stationary form in a continuum approximation of the finite-length phase. Numerical simulations of interacting filaments suggest an anomalous power-law divergence of the protrusion length at the growth transition, which could be a universal feature of cross-linked depolymerizing systems. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  17. 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

  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. 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

  20. 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.

  1. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Polyimide Aerogels Using Triisocyanate as Cross-linker.

    PubMed

    Nguyen, Baochau N; Meador, Mary Ann B; Scheiman, Daniel; McCorkle, Linda

    2017-08-16

    A family of polyimide (PI)-based aerogels is produced using Desmodur N3300A, an inexpensive triisocyanate, as the cross-linker. The aerogels are prepared by cross-linking amine end-capped polyimide oligomers with the triisocyanate. The polyimide oligomers are formulated using 2,2'-dimethylbenzidine, 4,4'-oxydianiline, or mixtures of both diamines, combined with 3,3',4,4'-biphenyltetracarboxylic dianhydride, and are chemically imidized at room temperature. Depending on the backbone chemistry, chain length, and polymer concentration, density of the aerogels ranged from 0.06 to 0.14 g/cm(3) and Brunauer-Emmett-Teller surface areas ranged from 350 to 600 m(2)/g. Compressive moduli of these aerogels were as high as 225 MPa, which are comparable to, or higher than, those previously reported prepared with similar backbone structures but with other cross-linkers. Because of their lower cost and commercial availability as cross-linker, the aerogels may have further potential as insulation for building and construction, clothing, sporting goods, and automotive applications, although lower-temperature stability may limit their use in some aerospace applications.

  3. 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.

  4. 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

  5. Design of polyzinc finger peptides with structured linkers

    PubMed Central

    Moore, Michael; Choo, Yen; Klug, Aaron

    2001-01-01

    Zinc finger domains are perhaps the most versatile of all known DNA binding domains. By fusing up to six zinc finger modules, which normally recognize up to 18 bp of DNA, designer transcription factors can be produced to target unique sequences within large genomes. However, not all continuous DNA sequences make good zinc finger binding sites. To avoid having to target unfavorable DNA sequences, we designed multizinc finger peptides with linkers capable of spanning long stretches of nonbound DNA. Two three-finger domains were fused by using either transcription factor IIIA for the Xenopus 5S RNA gene (TFIIIA) finger 4 or a non-sequence-specific zinc finger as a “structured” linker. Our gel-shift results demonstrate that these peptides are able to bind with picomolar affinities to target sequences containing 0–10 bp of nonbound DNA. Furthermore, these peptides display greater sequence selectivity and bind with higher affinity than similar six-finger peptides containing long, flexible linkers. These peptides are likely to be of use in understanding the behavior of polydactyl proteins in nature and in the targeting of human, animal, or plant genomes for numerous applications. We also suggest that in certain polydactyl peptides an individual finger can “flip” out of the major groove to allow its neighbors to bind shorter, nontarget DNA sequences. PMID:11171968

  6. 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}.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Carbohydrate-binding modules recognize fine substructures of cellulose.

    PubMed

    McLean, Bradley W; Boraston, Alisdair B; Brouwer, Darren; Sanaie, Nooshafarin; Fyfe, Colin A; Warren, R Antony J; Kilburn, Douglas G; Haynes, Charles A

    2002-12-27

    Competition isotherms are used to identify the set of cellulose substructures to which cellulose binding modules (CBMs) from families 2a, 3, 4, 9, and 17 bind. The experiments are based on coupling a unique fluorescent tag to each CBM in a manner that does not alter the natural binding properties of the CBM and therefore allows the surface and solution concentrations of each CBM to be monitored as a function of time and composition. Adsorption and surface exchange of like or competing CBMs are monitored using a range of cellulose preparations varying in both crystallinity and provenance. CBMs from families 2a, 3, 4, 9, and 17 are shown to recognize different physical forms of prepared cellulose. The demonstration of the very fine binding specificity of cellulose-specific CBMs implies that the polysaccharide targets of CBMs extend down to the resolution of cellulose microstructures.

  15. 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.

  16. ATPase modulated stress granules contain a diverse proteome and substructure

    PubMed Central

    Jain, Saumya; Wheeler, Joshua R.; Walters, Robert W.; Agrawal, Anurag; Barsic, Anthony; Parker, Roy

    2015-01-01

    SUMMARY Stress granules are mRNA-protein granules that form when translation initiation is limited and 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, 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. PMID:26777405

  17. Exposing the dead cone effect with jet substructure techniques

    NASA Astrophysics Data System (ADS)

    Maltoni, Fabio; Selvaggi, Michele; Thaler, Jesse

    2016-09-01

    The dead cone is a well-known effect in gauge theories, where radiation from a charged particle of mass m and energy E is suppressed within an angular size of m /E . This effect is universal as it does not depend on the spin of the particle nor on the nature of the gauge interaction. It is challenging to directly measure the dead cone at colliders, however, since the region of suppressed radiation either is too small to be resolved or is filled by the decay products of the massive particle. In this paper, we propose to use jet substructure techniques to expose the dead cone effect in the strong-force radiation pattern around boosted top quarks at the Large Hadron Collider. Our study shows that with 300 /fb of 13-14 TeV collision data, ATLAS and CMS could obtain the first direct evidence of the dead cone effect and test its basic features.

  18. 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

  19. 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.

  20. 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.

  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. Linker histone interaction shows divalent character with both supercoiled and linear DNA.

    PubMed

    Ellen, Thomas P; van Holde, K E

    2004-06-22

    The interaction of linker histone H1 with both linear and superhelical double-stranded DNA has been investigated at low ionic strengths. Gel mobility retardation experiments demonstrate strikingly different behavior for the two forms of DNA. First, the experiments strongly suggest that linker histone binds to superhelical DNA in a negatively cooperative mode. In contrast, binding of linker histone to linear DNA under the conditions employed here shows no cooperativity. Second, binding of linker histone to linear DNA results in aggregation of histone-DNA complexes, even at very low levels of input histone H1. Because H1 has been shown to interact as a monomer, this aggregation is evidence of the divalent character of the linker histone, for without H1's ability to bind to two duplex strands of DNA, aggregation could not occur. Although aggregation can be made to occur with superhelical DNA, it can do so only at near-saturation levels of input histone H1. Finally, in direct competition, linker histone binds to superhelical DNA to the complete exclusion of linear DNA, indicating that the linker histone's function is related to the crossover structures that differentiate superhelical DNA from linear DNA. We develop a model that explains the observed behavior of binding of linker histone to superhelical DNA that is consistent with both the divalent character of the linker histone and the negative cooperativity by which linker histone and superhelical DNA interact.

  3. 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.

  4. Propagation of uncertainty in test-analysis correlation of substructured spacecraft

    NASA Astrophysics Data System (ADS)

    Kammer, Daniel C.; Nimityongskul, Sonny

    2011-03-01

    Organizations, such as the Air Force and NASA make critical decisions on spacecraft performance and survivability based on the results of test-analysis correlation metrics. In order to ensure the success of a new paradigm in finite element model validation where there is no system level test, uncertainty in the substructures must be propagated into the system level correlation metrics. The objective of this work is to quantify the level of accuracy required at the substructure level to produce acceptable analytical model accuracy at the system level. In preparation for future synthesized system level uncertainty analysis, a framework is presented for propagating analytical model uncertainty from a fixed interface Craig-Bampton substructure representation into a free-free substructure. Model uncertainty is parameterized in terms of test- or truth-analysis correlation metrics that are dictated by the Air Force. A statistical model is presented for these correlation metrics such that an analyst can specify a covariance matrix for uncertainty in model correlation at the fixed substructure level, and then propagate it into correlation uncertainty at the free substructure level. Development of the forward propagation approach then allows propagation of correlation uncertainty in the reverse direction from the free substructure into the fixed interface based Craig-Bampton representation. The proposed methods are applied to a typical spacecraft representation.

  5. 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.

  6. 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.

  7. Dislocation Substructures Formed After Fracture of Deformed Polycrystalline Cu-Al Alloys

    NASA Astrophysics Data System (ADS)

    Koneva, N. A.; Trishkina, L. I.; Cherkasova, T. V.

    2017-08-01

    The paper deals with the dislocation substructure of polycrystalline FCC alloys modified by plastic deformation at a distance from the area of the specimen fracture. Observations are performed using the transmission electron microscopy. Cu-Al alloys with grain size ranging from 10 to 240 μm are studied in this paper. The parameters of the dislocation substructure are measured and their variation is determined by the increasing distance from the fracture area. It is shown how the grain size influences these processes. The different dislocation substructures which determine the specimen fracture at a mesocscale level are found herein.

  8. 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.

  9. Jet Substructure: Boosting the Search for New Physics at the LHC

    NASA Astrophysics Data System (ADS)

    Thaler, Jesse

    2016-03-01

    Collisions at the Large Hadron Collider (LHC) are dominated by jets, collimated sprays of particles that are proxies for underlying quarks and gluons. With the remarkable performance of the ATLAS and CMS detectors, jets can now be characterized not just by their overall direction and energy but also by their substructure. In this talk, I highlight the ways that jet substructure has enhanced the search for new physics at the LHC, including recent excitement over a possible diboson excess. I also explain how theoretical studies of jet substructure have taught us surprising lessons about the nature of the strong force.

  10. 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.

  11. 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.

  12. Association of Systemic Lupus Erythematosus Clinical Features with European Population Genetic Substructure

    PubMed Central

    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. PMID:22194982

  13. A transversal substructuring mode matching method applied to the acoustic analysis of dissipative mufflers

    NASA Astrophysics Data System (ADS)

    Albelda, J.; Denia, F. D.; Torres, M. I.; Fuenmayor, F. J.

    2007-06-01

    To carry out the acoustic analysis of dissipative silencers with uniform cross-section, the application of the mode matching method at the geometrical discontinuities is an attractive option from a computational point of view. The consideration of this methodology assumes, in general, that the modes associated with the transversal geometry of each element with uniform cross-section are known for the excitation frequencies considered in the analysis. The calculation of the transversal modes is not, however, a simple task when the acoustic system involves perforated elements and absorbent materials. The current work presents a modal approach to calculate the transversal modes and the corresponding axial wavenumbers for dissipative mufflers of uniform (but arbitrary) cross-section. The proposed technique is based on the division of the transversal section into subdomains and the subsequent use of a substructuring procedure with two sets of modes to improve the convergence. The former set of modes fulfils the condition of zero pressure at the common boundary between transversal subdomains while the latter satisfies the condition of zero derivative in the direction normal to the boundary. The approach leads to a versatile methodology with a moderate computational effort that can be applied to mufflers commonly found in real applications. To validate the procedure presented in this work, comparisons are provided with finite element predictions and results available in the literature, showing a good agreement. In addition, the procedure is applied to an example of practical interest.

  14. 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.

  15. 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.

  16. Multifunctionality of the linker histones: an emerging role for protein-protein interactions.

    PubMed

    McBryant, Steven J; Lu, Xu; Hansen, Jeffrey C

    2010-05-01

    Linker histones, e.g., H1, are best known for their ability to bind to nucleosomes and stabilize both nucleosome structure and condensed higher-order chromatin structures. However, over the years many investigators have reported specific interactions between linker histones and proteins involved in important cellular processes. The purpose of this review is to highlight evidence indicating an important alternative mode of action for H1, namely protein-protein interactions. We first review key aspects of the traditional view of linker histone action, including the importance of the H1 C-terminal domain. We then discuss the current state of knowledge of linker histone interactions with other proteins, and, where possible, highlight the mechanism of linker histone-mediated protein-protein interactions. Taken together, the data suggest a combinatorial role for the linker histones, functioning both as primary chromatin architectural proteins and simultaneously as recruitment hubs for proteins involved in accessing and modifying the chromatin fiber.

  17. Multifunctionality of the linker histones: an emerging role for protein-protein interactions

    PubMed Central

    McBryant, Steven J; Lu, Xu; Hansen, Jeffrey C

    2010-01-01

    Linker histones, e.g., H1, are best known for their ability to bind to nucleosomes and stabilize both nucleosome structure and condensed higher-order chromatin structures. However, over the years many investigators have reported specific interactions between linker histones and proteins involved in important cellular processes. The purpose of this review is to highlight evidence indicating an important alternative mode of action for H1, namely protein-protein interactions. We first review key aspects of the traditional view of linker histone action, including the importance of the H1 C-terminal domain. We then discuss the current state of knowledge of linker histone interactions with other proteins, and, where possible, highlight the mechanism of linker histone-mediated protein-protein interactions. Taken together, the data suggest a combinatorial role for the linker histones, functioning both as primary chromatin architectural proteins and simultaneously as recruitment hubs for proteins involved in accessing and modifying the chromatin fiber. PMID:20309017

  18. Investigation of the redox property of a metalloprotein layer self-assembled on various chemical linkers.

    PubMed

    Chung, Yong-Ho; Lee, Taek; Min, Junhong; Choi, Jeong-Woo

    2011-10-01

    Myogloblin, a well-known metalloprotein, was immobilized on a gold surface using various chemical linkers to investigate the length effect of chemical linker on the electron transfer in protein layers, because chemical linkers play roles in the pathway that transfers the electron from the protein to the gold substrate and act as protein immobilization reagents. Chemical linkers with 2, 6, 11, and 16 carbons were utilized to confirm length-effects. The immobilization of protein and chemical linker was validated with surface plasmon resonance (SPR) and atomic force microscopy (AFM). The electrochemical property was evaluated by cyclic voltammetry (CV) and chronocoulometry (CC). In those results, redox peaks of immobilized protein were controlled via the length of chemical linkers, and it could be directly applied to the realization of bioelectronic device. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Wear performance of substructure ceramics and veneering porcelains.

    PubMed

    Preis, Verena; Behr, Michael; Kolbeck, Carola; Hahnel, Sebastian; Handel, Gerhard; Rosentritt, Martin

    2011-08-01

    The aim of this in vitro study was to compare the two-body wear resistance of substructure zirconia and veneering porcelain versus steatite and human enamel antagonists, respectively. Two-body wear tests were performed in a chewing simulator with steatite and enamel antagonists (enamel cusps). A pin-on-block design with a vertical load of 50 N for 1.2 × 10(5) cycles; (f=1.6 Hz; lateral movement: 1mm, mouth opening: 2mm) was used for the wear test. For quantification of the wear resistance, wear tests were performed with standardized steatite spheres. Human enamel was used as a reference. Five zirconia ceramics and four veneering porcelains were investigated. One zirconia ceramic was tested with superficial glaze, which was applied after polishing or sandblasting, respectively. Surface roughness R(a) (SP6, Perthen-Feinprüf, G) and wear depth were determined using a 3D-Profilometer (Laserscan 3D, Willytec, G). SEM (Quanta FEG 400, FEI, USA) pictures were used for evaluating wear performance of both, ceramics and antagonists. No wear was found for zirconia substructures. Veneering porcelain provided wear traces between 186.1±33.2 μm and 232.9±66.9 μm (steatite antagonist) and 90.6±3.5 μm and 123.9±50.7 μm (enamel). Wear of the steatite antagonists varied between 0.812±0.256 mm(2) and 1.360±0.321 mm(2) for zirconia and 1.708±0.275 mm(2) and 2.568±0.827 mm(2) for porcelain. Enamel generally showed wear, cracks or even fractures at the ridge, regardless whether opposed by zirconia or porcelain/glaze. Enamel was polished, when opposed to zirconia, or plowed, provoked and grinded, when opposed to porcelain/glaze. The results of the wear test with steatite or enamel antagonists indicated no measurable wear on zirconia surfaces. Porcelain showed higher wear than zirconia, but comparable or lower wear than an enamel reference. Antagonistic wear against zirconia was found to be lower than wear against porcelain. Copyright © 2011 Academy of Dental Materials

  20. 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

  1. Heterobifunctional Dyes: Highly Fluorescent Linkers Based on Cyanine Dyes

    PubMed Central

    Wycisk, Virginia; Achazi, Katharina; Hirsch, Ole; Kuehne, Christian; Dernedde, Jens; Haag, Rainer

    2017-01-01

    Abstract Herein, we present a new synthetic route to cyanine‐based heterobifunctional dyes and their application as fluorescent linkers between polymers and biomolecules. The synthesized compounds, designed in the visible spectral range, are equipped with two different reactive groups for highly selective conjugation under physiological conditions. By applying indolenine precursors with functionalized benzenes, we achieved water‐soluble asymmetric cyanine dyes bearing maleimido and N‐hydroxysuccinimidyl functionalities in a three‐step synthesis. Spectroscopic characterization revealed good molar absorption coefficients and moderate fluorescence quantum yields. Further reaction with polyethylene glycol yielded dye–polymer conjugates that were subsequently coupled to the antibody cetuximab, often applied in cancer therapy. Successful coupling was confirmed by mass shifts detected by gel electrophoresis. Receptor‐binding studies and live‐cell imaging revealed that labeling did not alter the biological function. In sum, we provided a successful synthetic pathway to rigid heterobifunctional cyanine dyes that are applicable as fluorescent linkers, for example, for connecting antibodies with macromolecules. Our approach contributes to the field of bioconjugation chemistry, such as antibody–drug conjugates by combining diagnostic and therapeutic approaches. PMID:28638777

  2. Melting transition in lipid vesicles functionalised by mobile DNA linkers.

    PubMed

    Bachmann, Stephan Jan; Kotar, Jurij; Parolini, Lucia; Šarić, Anđela; Cicuta, Pietro; Di Michele, Lorenzo; Mognetti, Bortolo Matteo

    2016-09-20

    We study phase behaviour of lipid-bilayer vesicles functionalised by ligand-receptor complexes made of synthetic DNA by introducing a modelling framework and a dedicated experimental platform. In particular, we perform Monte Carlo simulations that combine a coarse grained description of the lipid bilayer with state of art analytical models for multivalent ligand-receptor interactions. Using density of state calculations, we derive the partition function in pairs of vesicles and compute the number of ligand-receptor bonds as a function of temperature. Numerical results are compared to microscopy and fluorimetry experiments on large unilamellar vesicles decorated by DNA linkers carrying complementary overhangs. We find that vesicle aggregation is suppressed when the total number of linkers falls below a threshold value. Within the model proposed here, this is due to the higher configurational costs required to form inter-vesicle bridges as compared to intra-vesicle loops, which are in turn related to membrane deformability. Our findings and our numerical/experimental methodologies are applicable to the rational design of liposomes used as functional materials and drug delivery applications, as well as to study inter-membrane interactions in living systems, such as cell adhesion.

  3. 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.

  4. PEGylation with the thiosuccinimido butylamine linker significantly increases the stability of haloalkane dehalogenase DhaA.

    PubMed

    Zhao, Yuan-Zhong; Yu, Wei-Li; Zheng, He; Guo, Xuan; Guo, Nan; Hu, Tao; Zhong, Jin-Yi

    2017-07-20

    Haloalkane dehalogenase (HLD) can catalyze the hydrolytic dehalogenation of halogenated compounds. However, HLD suffers from the poor stability to resist the environmental stress. PEGylation is an effective approach to enhance the stability of enzymes. The linker is an important stabilization factor of PEGylation. Thus, the linkers of the PEGylated HLD were optimized to improve the stability of HLD in the present study. The PEGylated haloalkane dehalogenase DhaAs with methylamine (Ml), carbamate (Cm) and thiosuccinimido butylamine (Tb) linkers were prepared, respectively. The effects of the Ml, Cm and Tb linkers on the stability of the PEGylated DhaAs were investigated under different environmental stresses. Among the three linkers, the Tb linker showed the highest efficacy to improve the stability of the PEGylated DhaA. The Tb linker significantly increased the thermal stability of the PEGylated DhaA by slowing its structural unfolding, and the pH stability of the PEGylated DhaA by slowing the protonation process. In addition, the PEGylated DhaA with the Tb linker showed the maximum resistance to high ionic strength (1M NaCl) and organic solvent (40% DMSO). PEGylation with the Tb linker is of general interest to effectively improve the stability of proteins, particularly the protein with poor stability. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. Jet substructure and probes of CP violation in Vh production

    NASA Astrophysics Data System (ADS)

    Godbole, R. M.; Miller, D. J.; Mohan, K. A.; White, C. D.

    2015-04-01

    We analyse the hVV ( V = W, Z) vertex in a model independent way using Vh production. To that end, we consider possible corrections to the Standard Model Higgs Lagrangian, in the form of higher dimensional operators which parametrise the effects of new physics. In our analysis, we pay special attention to linear observables that can be used to probe CP violation in the same. By considering the associated production of a Higgs boson with a vector boson ( W or Z), we use jet substructure methods to define angular observables which are sensitive to new physics effects, including an asymmetry which is linearly sensitive to the presence of CP odd effects. We demonstrate how to use these observables to place bounds on the presence of higher dimensional operators, and quantify these statements using a log likelihood analysis. Our approach allows one to probe separately the hZZ and hWW vertices, involving arbitrary combinations of BSM operators, at the Large Hadron Collider.

  10. 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.

  11. A halo substructure in Gaia Data Release 1

    NASA Astrophysics Data System (ADS)

    Myeong, G. C.; Evans, N. W.; Belokurov, V.; Koposov, S. E.; Sanders, J. L.

    2017-07-01

    We identify a halo substructure in the Tycho Gaia Astrometric Solution (TGAS) data set, cross-matched with the Radial Velocity Experiment (RAVE-on) data release. After quality cuts, the stars with large radial action (JR > 800 km s-1 kpc) are extracted. A subset of these stars is clustered in longitude and velocity and can be selected with further cuts. The 14 stars are centred on (X, Y, Z) ≈ (9.0, -1.0, -0.6) kpc and form a coherently moving structure in the halo with median (vR, vϕ, vz) = (167.33, 0.86, -94.85) km s-1. They are all metal-poor giants with median [Fe/H] = -0.83. To guard against the effects of distance errors, we compute spectrophotometric distances for 8 out of the 14 stars where this is possible. We find that six of the stars are still comoving. These six stars also have a much tighter [Fe/H] distribution ˜-0.7 with one exception ([Fe/H] = -2.12). We conclude that the existence of the comoving cluster is stable against changes in distance estimation and conjecture that this is the dissolving remnant of a globular cluster accreted long ago.

  12. Detecting dark matter substructure with narrow line lensing

    NASA Astrophysics Data System (ADS)

    Nierenberg, Anna

    2014-10-01

    The abundance of low mass halos is one of the key predictions of LCDM and remains at apparent odds with observations of luminous structure. Strong gravitational lensing provides a straightforward means of testing this theory as it enables the detection of dark matter subhalos at cosmological distances, without requiring the structure to contain any baryons at all. The fluxes of strongly lensed, parsec scale sources in particular, are excellent probes as they are extremely sensitive to the presence of low mass subhalos, while still being extended enough to remain unaffected by microlensing by stars which is a dominant contaminant for smaller sources. Traditionally this field has been limited to the analysis of the small number of strongly lensed, radio-loud quasars. Quasar narrow-line emission offers an alternative to radio. It is also parsec scale and microlensing free, but has the benefit of detectable in a much larger sample of systems. This proposal will combine milliarcsecond astrometry, and percent level photometry attainable with WFC3 IR grism, in order to measure spatially resolved narrow line lensing in six new systems, which cannot be studied from the ground. We have demonstrated that data of this quality can be used to detect subhalos as small as a million solar masses. This proposal will double the sample of systems which can be used to detect dark, low mass substructure using flux ratio anomalies.

  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. Searches for new physics with boosted objects and substructure with the ATLAS detector

    NASA Astrophysics Data System (ADS)

    López Mateos, D.; Atlas Collaboration

    2017-07-01

    The use of substructure in the ATLAS experiment has matured during the Run 1 analysis period into the most powerful new tool for understanding high- p_T physics at the LHC. In this document we present the studies that have been instrumental in reaching that maturity for boosted hadronic W/ Z , Higgs and top tagging. We also summarize the results from Run 1 and Run 2 searches for new physics using substructure, thus demonstrating the power of these new techniques.

  16. 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.

  17. Compressing the free energy range of substructure stabilities in iso-1-cytochrome c

    PubMed Central

    Duncan, Michael G; Williams, Michael D; Bowler, Bruce E

    2009-01-01

    Evolutionary conservation of substructure architecture between yeast iso-1-cytochrome c and the well-characterized horse cytochrome c is studied with limited proteolysis, the alkaline conformational transition and global unfolding with guanidine-HCl. Mass spectral analysis of limited proteolysis cleavage products for iso-1-cytochrome c show that its least stable substructure is the same as horse cytochrome c. The limited proteolysis data yield a free energy of 3.8 ± 0.4 kcal mol−1 to unfold the least stable substructure compared with 5.05 ± 0.30 kcal mol−1 for global unfolding of iso-1-cytochrome c. Thus, substructure stabilities of iso-1-cytochrome c span only ∼1.2 kcal mol−1 compared with ∼8 kcal mol−1 for horse cytochrome c. Consistent with the less cooperative folding thus expected for the horse protein, the guanidine-HCl m-values are ∼3 kcal mol−1M−1 versus ∼4.5 kcal mol−1M−1 for horse versus yeast cytochrome c. The tight free energy spacing of the yeast cytochrome c substructures suggests that its folding has more branch points than for horse cytochrome c. Studies on a variant of iso-1-cytochrome c with an H26N mutation indicate that the least and most stable substructures unfold sequentially and the two least stable substructures unfold independently as for horse cytochrome c. Thus, important aspects of the substructure architecture of horse cytochrome c, albeit compressed energetically, are preserved evolutionally in yeast iso-1-cytochrome c. PMID:19472325

  18. 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.

  19. 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

  20. Extreme Brightness Temperatures and Refractive Substructure in 3C273 with RadioAstron

    NASA Astrophysics Data System (ADS)

    Johnson, Michael D.; Kovalev, Yuri Y.; Gwinn, Carl R.; Gurvits, Leonid I.; Narayan, Ramesh; Macquart, Jean-Pierre; Jauncey, David L.; Voitsik, Peter A.; Anderson, James M.; Sokolovsky, Kirill V.; Lisakov, Mikhail M.

    2016-03-01

    Earth-space interferometry with RadioAstron provides the highest direct angular resolution ever achieved in astronomy at any wavelength. RadioAstron detections of the classic quasar 3C 273 on interferometric baselines up to 171,000 km suggest brightness temperatures exceeding expected limits from the “inverse-Compton catastrophe” by two orders of magnitude. We show that at 18 cm, these estimates most likely arise from refractive substructure introduced by scattering in the interstellar medium. We use the scattering properties to estimate an intrinsic brightness temperature of 7× {10}12 {{K}}, which is consistent with expected theoretical limits, but which is ˜15 times lower than estimates that neglect substructure. At 6.2 cm, the substructure influences the measured values appreciably but gives an estimated brightness temperature that is comparable to models that do not account for the substructure. At 1.35 {{cm}}, the substructure does not affect the extremely high inferred brightness temperatures, in excess of {10}13 {{K}}. We also demonstrate that for a source having a Gaussian surface brightness profile, a single long-baseline estimate of refractive substructure determines an absolute minimum brightness temperature, if the scattering properties along a given line of sight are known, and that this minimum accurately approximates the apparent brightness temperature over a wide range of total flux densities.

  1. 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.

  2. Expression analysis of mammalian linker-histone subtypes.

    PubMed

    Medrzycki, Magdalena; Zhang, Yunzhe; Cao, Kaixiang; Fan, Yuhong

    2012-03-19

    Linker histone H1 binds to the nucleosome core particle and linker DNA, facilitating folding of chromatin into higher order structure. H1 is essential for mammalian development and regulates specific gene expression in vivo. Among the highly conserved histone proteins, the family of H1 linker histones is the most heterogeneous group. There are 11 H1 subtypes in mammals that are differentially regulated during development and in different cell types. These H1 subtypes include 5 somatic H1s (H1a-e), the replacement H1(0), 4 germ cell specific H1 subtypes, and H1x. The presence of multiple H1 subtypes that differ in DNA binding affinity and chromatin compaction ability provides an additional level of modulation of chromatin function. Thus, quantitative expression analysis of individual H1 subtypes, both of mRNA and proteins, is necessary for better understanding of the regulation of higher order chromatin structure and function. Here we describe a set of assays designed for analyzing the expression levels of individual H1 subtypes. mRNA expression of various H1 variant genes is measured by a set of highly sensitive and quantitative reverse transcription-PCR (qRT-PCR) assays, which are faster, more accurate and require much less samples compared with the alternative approach of Northern blot analysis. Unlike most other cellular mRNA messages, mRNAs for most histone genes, including the majority of H1 genes, lack a long polyA tail, but contain a stem-loop structure at the 3' untranslated region (UTR). Therefore, cDNAs are prepared from total RNA by reverse transcription using random primers instead of oligo-dT primers. Realtime PCR assays with primers specific to each H1 subtypes are performed to obtain highly quantitative measurement of mRNA levels of individual H1 subtypes. Expression of housekeeping genes are analyzed as controls for normalization. The relative abundance of proteins of each H1 subtype and core histones is obtained through reverse phase high

  3. 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

  4. Dependence of the Linker Histone and Chromatin Condensation on the Nucleosome Environment.

    PubMed

    Perišić, Ognjen; Schlick, Tamar

    2017-08-24

    The linker histone (LH), an auxiliary protein that can bind to chromatin and interact with the linker DNA to form stem motifs, is a key element of chromatin compaction. By affecting the chromatin condensation level, it also plays an active role in gene expression. However, the presence and variable concentration of LH in chromatin fibers with different DNA linker lengths indicate that its folding and condensation are highly adaptable and dependent on the immediate nucleosome environment. Recent experimental studies revealed that the behavior of LH in mononucleosomes markedly differs from that in small nucleosome arrays, but the associated mechanism is unknown. Here we report a structural analysis of the behavior of LH in mononucleosomes and oligonucleosomes (2-6 nucleosomes) using mesoscale chromatin simulations. We show that the adapted stem configuration heavily depends on the strength of electrostatic interactions between LH and its parental DNA linkers, and that those interactions tend to be asymmetric in small oligonucleosome systems. Namely, LH in oligonucleosomes dominantly interacts with one DNA linker only, as opposed to mononucleosomes where LH has similar interactions with both linkers and forms a highly stable nucleosome stem. Although we show that the LH condensation depends sensitively on the electrostatic interactions with entering and exiting DNA linkers, other interactions, especially by nonparental cores and nonparental linkers, modulate the structural condensation by softening LH and thus making oligonucleosomes more flexible, in comparison to to mono- and dinucleosomes. We also find that the overall LH/chromatin interactions sensitively depend on the linker length because the linker length determines the maximal nucleosome stem length. For mononucleosomes with DNA linkers shorter than LH, LH condenses fully, while for DNA linkers comparable or longer than LH, the LH extension in mononucleosomes strongly follows the length of DNA linkers

  5. 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.

  6. 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.

  7. A New Methodology for Incorporating Chiral Linkers into Stapled Peptides.

    PubMed

    Serrano, Juan C; Sipthorp, James; Xu, Wenshu; Itzhaki, Laura S; Ley, Steven V

    2017-06-19

    Stapled peptides have arisen as a new class of chemical probe and potential therapeutic agents for modulating protein-protein interactions. Here, we report the first two-component i,i+7 stapling methodology that makes use of two orthogonal, on-resin stapling reactions to incorporate linkers bearing a chiral centre into a p53-derived stapled peptide. Post-stapling modifications to the chain were performed on-resin and enabled rapid access to various peptide derivatives from a single staple. The stapled peptides have increased helicity, protease stability and in vitro binding affinities to MDM2 compared to the equivalent unstapled peptide. This approach can be used to generate a library of diverse stapled peptides with different properties starting from a single stapled peptide, with scope for much greater functional diversity than that provided by existing stapling methodologies. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  8. SWI/SNF chromatin remodeling and linker histones in plants.

    PubMed

    Jerzmanowski, Andrzej

    2007-01-01

    In yeast and mammals, ATP-dependent chromatin remodeling complexes belonging to the SWI/SNF family play critical roles in the regulation of transcription, cell proliferation, differentiation and development. Homologs of conserved subunits of SWI/SNF-type complexes, including several putative ATPases and other core subunits, have been identified in plants. Here I summarize recent insights in structural organization and functional diversification of putative plant SWI/SNF-type chromatin remodeling complexes and discuss in a broader evolutionary perspective the similarities and differences between plant and yeast/animal SWI/SNF remodeling. I also summarize the current view of localization in nucleosome and dynamic behaviour in chromatin of linker (H1) histones and discuss significance of recent findings indicating that in both plants and mammals histone H1 is involved in determining patterns of DNA methylation at selected loci.

  9. 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.

  10. The effects of varying cosmological parameters on halo substructure

    SciTech Connect

    Dooley, Gregory A.; Griffen, Brendan F.; Ji, Alexander P.; Vogelsberger, Mark; Frebel, Anna; Zukin, Phillip; Hernquist, Lars E.

    2014-05-01

    We investigate how different cosmological parameters, such as those delivered by the WMAP and Planck missions, affect the nature and evolution of the dark matter halo substructure. We use a series of flat Λ cold dark matter cosmological N-body simulations of structure formation, each with a different power spectrum but with the same initial white noise field. Our fiducial simulation is based on parameters from the WMAP seventh year cosmology. We then systematically vary the spectral index, n{sub s} ; matter density, Ω {sub M}; and normalization of the power spectrum, σ{sub 8}, for seven unique simulations. Across these, we study variations in the subhalo mass function, mass fraction, maximum circular velocity function, spatial distribution, concentration, formation times, accretion times, and peak mass. We eliminate dependence of subhalo properties on host halo mass and average the values over many hosts to reduce variance. While the 'same' subhalos from identical initial overdensity peaks in higher σ{sub 8}, n{sub s} , and Ω {sub m} simulations accrete earlier and end up less massive and closer to the halo center at z = 0, the process of continuous subhalo accretion and destruction leads to a steady state distribution of these properties across all subhalos in a given host. This steady state mechanism eliminates cosmological dependence on all of the properties listed above except for subhalo concentration and V {sub max}, which remain greater for higher σ{sub 8}, n{sub s} , and Ω {sub m} simulations, and subhalo formation time, which remains earlier. We also find that the numerical technique for computing the scale radius and the halo finder that were used can significantly affect the concentration-mass relationship as computed for a simulation.

  11. 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.

  12. Discovering Higgs Bosons of the MSSM using Jet Substructure

    SciTech Connect

    Kribs, Graham D.; Martin, Adam; Roy, Tuhin S.; Spannowsky, Michael

    2010-06-01

    We present a qualitatively new approach to discover Higgs bosons of the MSSM at the LHC using jet substructure techniques applied to boosted Higgs decays. These techniques are ideally suited to the MSSM, since the lightest Higgs boson overwhelmingly decays to b{bar b} throughout the entire parameter space, while the heavier neutral Higgs bosons, if light enough to be produced in a cascade, also predominantly decay to b{bar b}. The Higgs production we consider arises from superpartner production where superpartners cascade decay into Higgs bosons. We study this mode of Higgs production for several superpartner hierarchies: m{sub {tilde q}},m{sub {tilde g}} > m{sub {tilde W}},{sub {tilde B}} > m{sub h} + {mu}; m{tilde q};m{sub {tilde q}},m{sub {tilde g}} > m{sub {tilde W}},{sub {tilde B}} > m {sub h,H,A} + {mu}; and m{sub {tilde q}},m{sub {tilde g}} > m{sub {tilde W}} > m{sub h} + {mu} with m{sub {tilde B}} {approx} {mu}. In these cascades, the Higgs bosons are boosted, with pT > 200 GeV a large fraction of the time. Since Higgs bosons appear in cascades originating from squarks and/or gluinos, the cross section for events with at least one Higgs boson can be the same order as squark/gluino production. Given 10 fb{sup -1} of 14 TeV LHC data, with m{sub {tilde q}} {approx}< 1 TeV, and one of the above superpartner mass hierarchies, our estimate of S{radical} B of the Higgs signal is sufficiently high that the b{bar b} mode can become the discovery mode of the lightest Higgs boson of the MSSM.

  13. The Effects of Varying Cosmological Parameters on Halo Substructure

    NASA Astrophysics Data System (ADS)

    Dooley, Gregory A.; Griffen, Brendan F.; Zukin, Phillip; Ji, Alexander P.; Vogelsberger, Mark; Hernquist, Lars E.; Frebel, Anna

    2014-05-01

    We investigate how different cosmological parameters, such as those delivered by the WMAP and Planck missions, affect the nature and evolution of the dark matter halo substructure. We use a series of flat Λ cold dark matter cosmological N-body simulations of structure formation, each with a different power spectrum but with the same initial white noise field. Our fiducial simulation is based on parameters from the WMAP seventh year cosmology. We then systematically vary the spectral index, ns ; matter density, Ω M ; and normalization of the power spectrum, σ8, for seven unique simulations. Across these, we study variations in the subhalo mass function, mass fraction, maximum circular velocity function, spatial distribution, concentration, formation times, accretion times, and peak mass. We eliminate dependence of subhalo properties on host halo mass and average the values over many hosts to reduce variance. While the "same" subhalos from identical initial overdensity peaks in higher σ8, ns , and Ω m simulations accrete earlier and end up less massive and closer to the halo center at z = 0, the process of continuous subhalo accretion and destruction leads to a steady state distribution of these properties across all subhalos in a given host. This steady state mechanism eliminates cosmological dependence on all of the properties listed above except for subhalo concentration and V max, which remain greater for higher σ8, ns , and Ω m simulations, and subhalo formation time, which remains earlier. We also find that the numerical technique for computing the scale radius and the halo finder that were used can significantly affect the concentration-mass relationship as computed for a simulation.

  14. 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.

  15. 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

  16. 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

  17. Knowledge Linkers and the Flow of Educational Information. An Occasional Paper from ERIC at Stanford.

    ERIC Educational Resources Information Center

    Farr, Richard S.

    The flow of knowledge from researchers to users is aided by knowledge linkers who activate the interpersonal network of communication within the target audience. The linker enters this network by contacting (through periodicals, mass media, conventions, and directly) individuals in the audience who are more active than others (gatekeepers). Once…

  18. Linker Installation: Engineering Pore Environment with Precisely Placed Functionalities in Zirconium MOFs.

    PubMed

    Yuan, Shuai; Chen, Ying-Pin; Qin, Jun-Sheng; Lu, Weigang; Zou, Lanfang; Zhang, Qiang; Wang, Xuan; Sun, Xing; Zhou, Hong-Cai

    2016-07-20

    Precise placement of multiple functional groups in a highly ordered metal-organic framework (MOF) platform allows the tailoring of the pore environment, which is required for advanced applications. To realize this, we present a comprehensive study on the linker installation method, in which a stable MOF with coordinatively unsaturated Zr6 clusters was employed and linkers bearing different functional groups were postsynthetically installed. A Zr-MOF with inherent missing linker sites, namely, PCN-700, was initially constructed under kinetic control. Twelve linkers with different substituents were then designed to study their effect on MOF formation kinetics and therefore resulting MOF structures. Guided by the geometrical analysis, linkers with different lengths were installed into a parent PCN-700, giving rise to 11 new MOFs and each bearing up to three different functional groups in predefined positions. Systematic variation of the pore volume and decoration of pore environment were realized by linker installation, which resulted in synergistic effects including an enhancement of H2 adsorption capacities of up to 57%. In addition, a size-selective catalytic system for aerobic alcohol oxidation reaction is built in PCN-700 through linker installation, which shows high activity and tunable size selectivity. Altogether, these results exemplify the capability of the linker installation method in the pore environment engineering of stable MOFs with multiple functional groups, giving an unparalleled level of control.

  19. Hemidesmosomal linker proteins regulate cell motility, invasion and tumorigenicity in oral squamous cell carcinoma derived cells.

    PubMed

    Rajeev Chaudhari, Pratik; Emlit Charles, Silvania; D'Souza, Zinia Charlotte; Murlidhar Vaidya, Milind

    2017-08-31

    BPAG1e and Plectin are hemidesmosomal linker proteins which anchor intermediate filament proteins to the cell surface through β4 integrin. Recent reports indicate that these proteins play a role in various cellular processes apart from their known anchoring function. However, the available literature is inconsistent. Further, the previous study from our laboratory suggested that Keratin8/18 pair promotes cell motility and tumor progression by deregulating β4 integrin signaling in oral squamous cell carcinoma (OSCC) derived cells. Based on these findings, we hypothesized that linker proteins may have a role in neoplastic progression of OSCC. Downregulation of hemidesmosomal linker proteins in OSCC derived cells resulted in reduced cell migration accompanied by alterations in actin organization. Further, decreased MMP9 activity led to reduced cell invasion in linker proteins knockdown cells. Moreover, loss of these proteins resulted in reduced tumorigenic potential. SWATH analysis demonstrated upregulation of N-Myc downstream regulated gene 1 (NDRG1) in linker proteins downregulated cells as compared to vector control cells. Further, the defects in phenotype upon linker proteins ablation were rescued upon loss of NDRG1 in linker proteins knockdown background. These data together indicate that hemidesmosomal linker proteins regulate cell motility, invasion and tumorigenicity possibly through NDRG1 in OSCC derived cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Construction of hierarchically porous metal–organic frameworks through linker labilization

    DOE PAGES

    Yuan, Shuai; Zou, Lanfang; Qin, Jun-Sheng; ...

    2017-05-25

    One major goal of metal–organic framework (MOF) research is the expansion of pore size and volume. Although many approaches have been attempted to increase the pore size of MOF materials, it is still a challenge to construct MOFs with precisely customized pore apertures for specific applications. W present a new method, namely linker labilization, to increase the MOF porosity and pore size, giving rise to hierarchical-pore architectures. Microporous MOFs with robust metal nodes and pro-labile linkers were initially synthesized. The mesopores were subsequently created as crystal defects through the splitting of a pro-labile-linker and the removal of the linker fragmentsmore » by acid treatment. We also demonstrate that linker labilization method can create controllable hierarchical porous structures in stable MOFs, which facilitates the diffusion and adsorption process of guest molecules to improve the performances of MOFs in adsorption and catalysis.« less

  1. 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.

  2. Construction of hierarchically porous metal-organic frameworks through linker labilization

    NASA Astrophysics Data System (ADS)

    Yuan, Shuai; Zou, Lanfang; Qin, Jun-Sheng; Li, Jialuo; Huang, Lan; Feng, Liang; Wang, Xuan; Bosch, Mathieu; Alsalme, Ali; Cagin, Tahir; Zhou, Hong-Cai

    2017-05-01

    A major goal of metal-organic framework (MOF) research is the expansion of pore size and volume. Although many approaches have been attempted to increase the pore size of MOF materials, it is still a challenge to construct MOFs with precisely customized pore apertures for specific applications. Herein, we present a new method, namely linker labilization, to increase the MOF porosity and pore size, giving rise to hierarchical-pore architectures. Microporous MOFs with robust metal nodes and pro-labile linkers were initially synthesized. The mesopores were subsequently created as crystal defects through the splitting of a pro-labile-linker and the removal of the linker fragments by acid treatment. We demonstrate that linker labilization method can create controllable hierarchical porous structures in stable MOFs, which facilitates the diffusion and adsorption process of guest molecules to improve the performances of MOFs in adsorption and catalysis.

  3. Construction of hierarchically porous metal–organic frameworks through linker labilization

    PubMed Central

    Yuan, Shuai; Zou, Lanfang; Qin, Jun-Sheng; Li, Jialuo; Huang, Lan; Feng, Liang; Wang, Xuan; Bosch, Mathieu; Alsalme, Ali; Cagin, Tahir; Zhou, Hong-Cai

    2017-01-01

    A major goal of metal–organic framework (MOF) research is the expansion of pore size and volume. Although many approaches have been attempted to increase the pore size of MOF materials, it is still a challenge to construct MOFs with precisely customized pore apertures for specific applications. Herein, we present a new method, namely linker labilization, to increase the MOF porosity and pore size, giving rise to hierarchical-pore architectures. Microporous MOFs with robust metal nodes and pro-labile linkers were initially synthesized. The mesopores were subsequently created as crystal defects through the splitting of a pro-labile-linker and the removal of the linker fragments by acid treatment. We demonstrate that linker labilization method can create controllable hierarchical porous structures in stable MOFs, which facilitates the diffusion and adsorption process of guest molecules to improve the performances of MOFs in adsorption and catalysis. PMID:28541301

  4. 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.

  5. 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

  6. Rehabilitation of Nose following Chemical Burn Using CAD/CAM Made Substructure for Implant Retained Nasal Prosthesis: A Clinical Report

    PubMed Central

    Bhagat, Tushar; Verma, A. K.; Gurumurthy, Vishwanath; Ali, Mariyam; Vadhwani, Preeti

    2017-01-01

    Insufficient knowledge of medical chemicals and their improper use have destructive effects. Accidental exposure to chemicals on facial tissue may result in large facial defect. For ages the tradition of piercing nose is common but improper use of unknown chemical for piercing has deleterious effect. Mostly rhinectomy defects are acquired caused by trauma or malignant diseases. Prosthetic rehabilitation is the preferred treatment of choice for any large rhinectomy defects as medical and surgical interventions are ineffective in developing esthetics. Main concern with the prosthesis for such defects is retention. This article describes rehabilitation of a patient with large size nasal defect created by chemical burn in childhood during piercing. Implant retained customized silicone nasal prosthesis was fabricated using simple O-ring attachments and innovative modified polyamide acrylic resin substructure acting as skeleton. PMID:28702265

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. DARK MATTER SUBSTRUCTURE DETECTION USING SPATIALLY RESOLVED SPECTROSCOPY OF LENSED DUSTY GALAXIES

    SciTech Connect

    Hezaveh, Yashar; Holder, Gilbert; Dalal, Neal; Kuhlen, Michael; Marrone, Daniel; Murray, Norman; Vieira, Joaquin

    2013-04-10

    We investigate how strong lensing of dusty, star-forming galaxies (DSFGs) by foreground galaxies can be used as a probe of dark matter halo substructure. We find that spatially resolved spectroscopy of lensed sources allows dramatic improvements to measurements of lens parameters. In particular, we find that modeling of the full, three-dimensional (angular position and radial velocity) data can significantly facilitate substructure detection, increasing the sensitivity of observables to lower mass subhalos. We carry out simulations of lensed dusty sources observed by early ALMA (Cycle 1) and use a Fisher matrix analysis to study the parameter degeneracies and mass detection limits of this method. We find that even with conservative assumptions, it is possible to detect galactic dark matter subhalos of {approx}10{sup 8} M{sub Sun} with high significance in most lensed DSFGs. Specifically, we find that in typical DSFG lenses, there is a {approx}55% probability of detecting a substructure with M > 10{sup 8} M{sub Sun} with more than 5{sigma} detection significance in each lens, if the abundance of substructure is consistent with previous lensing results. The full ALMA array, with its significantly enhanced sensitivity and resolution, should improve these estimates considerably. Given the sample of {approx}100 lenses provided by surveys such as the South Pole Telescope, our understanding of dark matter substructure in typical galaxy halos is poised to improve dramatically over the next few years.

  13. Efficient substructure searching of large chemical libraries: the ABCD chemical cartridge.

    PubMed

    Agrafiotis, Dimitris K; Lobanov, Victor S; Shemanarev, Maxim; Rassokhin, Dmitrii N; Izrailev, Sergei; Jaeger, Edward P; Alex, Simson; Farnum, Michael

    2011-12-27

    Efficient substructure searching is a key requirement for any chemical information management system. In this paper, we describe the substructure search capabilities of ABCD, an integrated drug discovery informatics platform developed at Johnson & Johnson Pharmaceutical Research & Development, L.L.C. The solution consists of several algorithmic components: 1) a pattern mapping algorithm for solving the subgraph isomorphism problem, 2) an indexing scheme that enables very fast substructure searches on large structure files, 3) the incorporation of that indexing scheme into an Oracle cartridge to enable querying large relational databases through SQL, and 4) a cost estimation scheme that allows the Oracle cost-based optimizer to generate a good execution plan when a substructure search is combined with additional constraints in a single SQL query. The algorithm was tested on a public database comprising nearly 1 million molecules using 4,629 substructure queries, the vast majority of which were submitted by discovery scientists over the last 2.5 years of user acceptance testing of ABCD. 80.7% of these queries were completed in less than a second and 96.8% in less than ten seconds on a single CPU, while on eight processing cores these numbers increased to 93.2% and 99.7%, respectively. The slower queries involved extremely generic patterns that returned the entire database as screening hits and required extensive atom-by-atom verification.

  14. New constraints on the complex mass substructure in Abell 1689 from gravitational flexion

    NASA Astrophysics Data System (ADS)

    Leonard, Adrienne; King, Lindsay J.; Goldberg, David M.

    2011-05-01

    In a recent publication, the flexion aperture mass statistic was found to provide a robust and effective method by which substructure in galaxy clusters might be mapped. Moreover, we suggested that the masses and mass profile of structures might be constrained using this method. In this paper, we apply the flexion aperture mass technique to HST ACS images of Abell 1689. We demonstrate that the flexion aperture mass statistic is sensitive to small-scale structures in the central region of the cluster. While the central potential is not constrained by our method, due largely to missing data in the central 0.5 arcmin of the cluster, we are able to place constraints on the masses and mass profiles of prominent substructures. We identify four separate mass peaks, and use the peak aperture mass signal and zero signal radius in each case to constrain the masses and mass profiles of these substructures. The three most massive peaks exhibit complex small-scale structure, and the masses indicated by the flexion aperture mass statistic suggest that these three peaks represent the dominant substructure component of the cluster (˜7 × 1014 h-1 M⊙). Their complex structure indicates that the cluster - far from being relaxed - may have recently undergone a merger. The smaller, subsidiary peak is located coincident with a group of galaxies within the cluster, with mass ˜1 × 1014 h-1 M⊙. These results are in excellent agreement with previous substructure studies of this cluster.

  15. 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.

  16. Identification of population substructure among Jews using STR markers and dependence on reference populations included.

    PubMed

    Listman, Jennifer B; Hasin, Deborah; Kranzler, Henry R; Malison, Robert T; Mutirangura, Apiwat; Sughondhabirom, Atapol; Aharonovich, Efrat; Spivak, Baruch; Gelernter, Joel

    2010-06-14

    Detecting population substructure is a critical issue for association studies of health behaviors and other traits. Whether inherent in the population or an artifact of marker choice, determining aspects of a population's genetic history as potential sources of substructure can aid in design of future genetic studies. Jewish populations, among which association studies are often conducted, have a known history of migrations. As a necessary step in understanding population structure to conduct valid association studies of health behaviors among Israeli Jews, we investigated genetic signatures of this history and quantified substructure to facilitate future investigations of these phenotypes in this population. Using 32 autosomal STR markers and the program STRUCTURE, we differentiated between Ashkenazi (AJ, N = 135) and non-Ashkenazi (NAJ, N = 226) Jewish populations in the form of Northern and Southern geographic genetic components (AJ north 73%, south 23%, NAJ north 33%, south 60%). The ability to detect substructure within these closely related populations using a small STR panel was contingent on including additional samples representing major continental populations in the analyses. Although clustering programs such as STRUCTURE are designed to assign proportions of ancestry to individuals without reference population information, when Jewish samples were analyzed in the absence of proxy parental populations, substructure within Jews was not detected. Generally, for samples with a given grandparental country of birth, STRUCTURE assignment values to Northern, Southern, African and Asian clusters agreed with mitochondrial DNA and Y-chromosomal data from previous studies as well as historical records of migration and intermarriage.

  17. 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.

  18. Effect of the linkers between the zinc fingers in zinc finger protein 809 on gene silencing and nuclear localization

    SciTech Connect

    Ichida, Yu Utsunomiya, Yuko; Onodera, Masafumi

    2016-03-18

    Zinc finger protein 809 (ZFP809) belongs to the Kruppel-associated box-containing zinc finger protein (KRAB-ZFP) family and functions in repressing the expression of Moloney murine leukemia virus (MoMLV). ZFP809 binds to the primer-binding site (PBS)located downstream of the MoMLV-long terminal repeat (LTR) and induces epigenetic modifications at integration sites, such as repressive histone modifications and de novo DNA methylation. KRAB-ZFPs contain consensus TGEKP linkers between C2H2 zinc fingers. The phosphorylation of threonine residues within linkers leads to the inactivation of zinc finger binding to target sequences. ZFP809 also contains consensus linkers between zinc fingers. However, the function of ZFP809 linkers remains unknown. In the present study, we constructed ZFP809 proteins containing mutated linkers and examined their ability to silence transgene expression driven by MLV, binding ability to MLV PBS, and cellular localization. The results of the present study revealed that the linkers affected the ability of ZFP809 to silence transgene expression. Furthermore, this effect could be partly attributed to changes in the localization of ZFP809 proteins containing mutated linkers. Further characterization of ZFP809 linkers is required for understanding the functions and features of KRAB-ZFP-containing linkers. - Highlights: • ZFP809 has three consensus linkers between the zinc fingers. • Linkers are required for ZFP809 to silence transgene expression driven by MLV-LTR. • Linkers affect the precise nuclear localization of ZFP809.

  19. 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

  20. 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.

  1. 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. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. 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

  3. 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.

  4. Effect of Linker Structure on Surface Density of Aptamer Monolayers and their Corresponding Protein Binding Efficiency

    PubMed Central

    Balamurugan, Subramanian; Obubuafo, Anne; McCarley, Robin L.

    2009-01-01

    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 (T0, T5, T10, T20), the surface density of the aptamer decreased linearly from approximately 25 to 12 pmol•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 T5, 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. PMID:18989937

  5. 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

  6. Glycosylated linkers in multimodular lignocellulose-degrading enzymes dynamically bind to cellulose

    PubMed Central

    Payne, Christina M.; Resch, Michael G.; Chen, Liqun; Crowley, Michael F.; Himmel, Michael E.; Taylor, Larry E.; Sandgren, Mats; Ståhlberg, Jerry; Stals, Ingeborg; Tan, Zhongping; Beckham, Gregg T.

    2013-01-01

    Plant cell-wall polysaccharides represent a vast source of food in nature. To depolymerize polysaccharides to soluble sugars, many organisms use multifunctional enzyme mixtures consisting of glycoside hydrolases, lytic polysaccharide mono-oxygenases, polysaccharide lyases, and carbohydrate esterases, as well as accessory, redox-active enzymes for lignin depolymerization. Many of these enzymes that degrade lignocellulose are multimodular with carbohydrate-binding modules (CBMs) and catalytic domains connected by flexible, glycosylated linkers. These linkers have long been thought to simply serve as a tether between structured domains or to act in an inchworm-like fashion during catalytic action. To examine linker function, we performed molecular dynamics (MD) simulations of the Trichoderma reesei Family 6 and Family 7 cellobiohydrolases (TrCel6A and TrCel7A, respectively) bound to cellulose. During these simulations, the glycosylated linkers bind directly to cellulose, suggesting a previously unknown role in enzyme action. The prediction from the MD simulations was examined experimentally by measuring the binding affinity of the Cel7A CBM and the natively glycosylated Cel7A CBM-linker. On crystalline cellulose, the glycosylated linker enhances the binding affinity over the CBM alone by an order of magnitude. The MD simulations before and after binding of the linker also suggest that the bound linker may affect enzyme action due to significant damping in the enzyme fluctuations. Together, these results suggest that glycosylated linkers in carbohydrate-active enzymes, which are intrinsically disordered proteins in solution, aid in dynamic binding during the enzymatic deconstruction of plant cell walls. PMID:23959893

  7. Evidence for hard and soft substructures in thermoelectric SnSe

    NASA Astrophysics Data System (ADS)

    Popuri, S. R.; Pollet, M.; Decourt, R.; Viciu, M. L.; Bos, J. W. G.

    2017-06-01

    SnSe is a topical thermoelectric material with a low thermal conductivity which is linked to its unique crystal structure. We use low-temperature heat capacity measurements to demonstrate the presence of two characteristic vibrational energy scales in SnSe with Debye temperatures θD1 = 345(9) K and θD2 = 154(2) K. These hard and soft substructures are quantitatively linked to the strong and weak Sn-Se bonds in the crystal structure. The heat capacity model predicts the temperature evolution of the unit cell volume, confirming that this two-substructure model captures the basic thermal properties. Comparison with phonon calculations reveals that the soft substructure is associated with the low energy phonon modes that are responsible for the thermal transport. This suggests that searching for materials containing highly divergent bond distances should be a fruitful route for discovering low thermal conductivity materials.

  8. An Investigation of Power Flow Characteristics of L-Shaped Plates Adopting a Substructure Approach

    NASA Astrophysics Data System (ADS)

    WANG, Z. H.; XING, J. T.; PRICE, W. G.

    2002-02-01

    A substructure approach with free-free interface condition is formulated to investigate the power flow characteristics of an L-shaped plate. This is achieved by complementing the normal dynamic equations with geometric compatibility equations allowing the assessment of power flow dynamic characteristics applied to and excited within the system. The displacement contribution of the external and boundary coupling forces is deduced, permitting determination of the power flow between the interfaces of substructures. A power flow density vector is defined and the corresponding power flow lines illustrate the flow of power in the plate. Numerical examples demonstrate the applicability of the method and detailed configurations display the power flow characteristics associated with L-shaped plates. The proposed method can calculate the higher modes easily and efficiently to ensure convergence of solution as well as readily taking into account variations in substructure damping.

  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. 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.

  11. 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.

  12. 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.

  13. Mobile linkers on DNA-coated colloids: valency without patches.

    PubMed

    Angioletti-Uberti, Stefano; Varilly, Patrick; Mognetti, Bortolo M; Frenkel, Daan

    2014-09-19

    Colloids coated with single-stranded DNA (ssDNA) can bind selectively to other colloids coated with complementary ssDNA. The fact that DNA-coated colloids (DNACCs) can bind to specific partners opens the prospect of making colloidal "molecules." However, in order to design DNACC-based molecules, we must be able to control the valency of the colloids, i.e., the number of partners to which a given DNACC can bind. One obvious, but not very simple approach is to decorate the colloidal surface with patches of single-stranded DNA that selectively bind those on other colloids. Here we propose a design principle that exploits many-body effects to control the valency of otherwise isotropic colloids. Using a combination of theory and simulation, we show that we can tune the valency of colloids coated with mobile ssDNA, simply by tuning the nonspecific repulsion between the particles. Our simulations show that the resulting effective interactions lead to low-valency colloids self-assembling in peculiar open structures, very different from those observed in DNACCs with immobile DNA linkers.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. Structural optimization of the fibre-reinforced composite substructure in a three-unit dental bridge.

    PubMed

    Shi, Li; Fok, Alex S L

    2009-06-01

    Failures of fixed partial dentures (FPDs) made of fibre-reinforced composites (FRC) have been reported in many clinical and in vitro studies. The types of failure include debonding at the composite-tooth interface, delamination of the veneering material from the FRC substructure and fracture of the pontic. The design of the FRC substructure, i.e. the position and orientation of the fibres, will affect the fracture resistance of the FPD. The purpose of this study was to find an optimal arrangement of the FRC substructure, by means of structural optimization, which could minimize the failure-initiating stresses in a three-unit FPD. A structural optimization method mimicking biological adaptive growth was developed for orthotropic materials such as FRC and incorporated into the finite element (FE) program ABAQUS. Using the program, optimization of the fibre positions and directions in a three-unit FPD was carried out, the aim being to align the fibre directions with those of the maximum principal stresses. The optimized design was then modeled and analyzed to verify the improvements in mechanical performance of the FPD. Results obtained from the optimization suggested that the fibres should be placed at the bottom of the pontic, forming a U-shape substructure that extended into the connectors linking the teeth and the pontic. FE analyses of the optimized design indicated stress reduction in both the veneering composite and at the interface between the veneer and the FRC substructure. The optimized design obtained using FE-based structural optimization can potentially improve the fracture resistance of FPDs by reducing some of the failure-initiating stresses. Optimization methods can therefore be a useful tool to provide sound scientific guidelines for the design of FRC substructures in FPDs.

  20. 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.

  1. 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

  2. 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.

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

    PubMed Central

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

    2009-01-01

    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. PMID:18797476

  4. 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.

  5. 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

  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. 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.

  8. 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.

  9. 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.

  10. Samarium(II)-mediated linker cleavage-cyclization in fluorous synthesis: reactions of samarium enolates.

    PubMed

    James, Karen M; Willetts, Nigel; Procter, David J

    2008-03-20

    SmI2 has been used to cleave a sulfur linker and trigger cyclizations in strategies for the traceless fluorous synthesis of N-heterocycles. The studies give further insights into the reactivity of samarium enolates.

  11. Intercalating nucleic acids: the influence of linker length and intercalator type on their duplex stabilities.

    PubMed

    Christensen, Ulf B; Wamberg, Michael; El-Essawy, Farag A G; Ismail, Abd El-Hamid; Nielsen, Christina B; Filichev, Vyacheslav V; Jessen, Carsten H; Petersen, Michael; Pedersen, Erik B

    2004-01-01

    Six new examples of intercalating nucleic acids were synthesized in order to evaluate the dependence of the length of the linker between oligo and intercalator on the thermal stability of their corresponding duplexes and triplexes.

  12. 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.

  13. Carbon nanotubes functionalized with folic acid attached via biomimetic peptide linker.

    PubMed

    Fraczyk, Justyna; Walczak, Malgorzata; Szymanski, Lukasz; Kolacinski, Zbigniew; Wrzosek, Henryk; Majsterek, Ireneusz; Przybylowska-Sygut, Karolina; Kaminski, Zbigniew J

    2017-09-01

    Anchoring folic acid (FA) with a biomimetic peptidic linker resistant to proteolytic degradation to act as a homing device on functionalized carbon nanotubes. Ethylenediamine was attached to oxidized multiwalled carbon nanotubes (MWNTs) using 4-(4,6-dimethoxy-[1,3,5]triazin-2-yl)-4-methylmorpholinium tetrafluoroborate. FA was coupled with 6-aminohexanoic acid and derivatives of β-alanine, affording four intermediates, which connected to the MWNTs via peptidic linkers of various lengths. Biomimetic nanomaterials were produced with FA as a homing molecule. The structure and properties of the nanomaterials were analyzed, confirming the versatility of the peptides used as linkers. Conjugates of FA attached to MWNTs via peptide linkers prepared from β-alanine residues are resistant to proteolytic degradation. Viability in colon cancer cells and normal colonocytes confirmed their lack of cytotoxicity.

  14. 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

  15. Identification of novel post-translational modifications in linker histones from chicken erythrocytes.

    PubMed

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

    2015-01-15

    Chicken erythrocyte nuclei were digested with micrococcal nuclease and fractionated by centrifugation in low-salt buffer into soluble and insoluble fractions. Post-translational modifications of the purified linker histones of both fractions were analyzed by LC-ESI-MS/MS. All six histone H1 subtypes (H1.01, H1.02, H1.03, H1.10, H1.1L and H1.1R) and histone H5 were identified. Mass spectrometry analysis enabled the identification of a wide range of PTMs, including N(α)-terminal acetylation, acetylation, formylation, phosphorylation and oxidation. A total of nine new modifications in chicken linker histones were mapped, most of them located in the N-terminal and globular domains. Relative quantification of the modified peptides showed that linker histone PTMs were differentially distributed among both chromatin fractions, suggesting their relevance in the regulation of chromatin structure. The analysis of our results combined with previously reported data for chicken and some mammalian species showed that most of the modified positions were conserved throughout evolution, highlighting their importance in specific linker histone functions and epigenetics. Post-translational modifications of linker histones could have a role in the regulation of gene expression through the modulation of chromatin higher-order structure and chromatin remodeling. Finding new PTMs in linker histones is the first step to elucidate their role in the histone code. In this manuscript we report nine new post-translational modifications of the linker histones from chicken erythrocytes, one in H5 and eight in the H1 subtypes. Chromatin fractionated by centrifugation in low-salt buffer resulted in two fractions with different contents and compositions of linker histones and enriched in specific core histone PTMs. Of particular interest is the fact that linker histone PTMs were differentially distributed in both chromatin fractions, suggesting specific functions. Future studies are needed to

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

    PubMed Central

    Collepardo-Guevara, Rosana; Schlick, Tamar

    2014-01-01

    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. PMID:24847063

  17. 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.

  18. Novel Concepts of MS-Cleavable Cross-linkers for Improved Peptide Structure Analysis

    NASA Astrophysics Data System (ADS)

    Hage, Christoph; Falvo, Francesco; Schäfer, Mathias; Sinz, Andrea

    2017-10-01

    The chemical cross-linking/mass spectrometry (MS) approach is gaining increasing importance as an alternative method for studying protein conformation and for deciphering protein interaction networks. This study is part of our ongoing efforts to develop innovative cross-linking principles for a facile and efficient assignment of cross-linked products. We evaluate two homobifunctional, amine-reactive, and MS-cleavable cross-linkers regarding their potential for automated analysis of cross-linked products. We introduce the bromine phenylurea (BrPU) linker that possesses a unique structure yielding a distinctive fragmentation pattern on collisional activation. Moreover, BrPU delivers the characteristic bromine isotope pattern and mass defect for all cross-linker-decorated fragments. We compare the fragmentation behavior of the BrPU linker with that of our previously described MS-cleavable TEMPO-Bz linker (which consists of a 2,2,6,6-tetramethylpiperidine-1-oxy moiety connected to a benzyl group) that was developed to perform free-radical-initiated peptide sequencing. Comparative collisional activation experiments (collision-induced dissociation and higher-energy collision-induced dissociation) with both cross-linkers were conducted in negative electrospray ionization mode with an Orbitrap Fusion mass spectrometer using five model peptides. As hypothesized in a previous study, the presence of a cross-linked N-terminal aspartic acid residue seems to be the prerequisite for the loss of an intact peptide from the cross-linked products. As the BrPU linker combines a characteristic mass shift with an isotope signature, it presents a more favorable combination for automated assignment of cross-linked products compared with the TEMPO-Bz linker. [Figure not available: see fulltext.

  19. Lecithin-linker formulations for self-emulsifying delivery of nutraceuticals.

    PubMed

    Chu, Jacquelene; Cheng, Yu-Ling; Rao, A Venketeshwer; Nouraei, Mehdi; Zarate-Muñoz, Silvia; Acosta, Edgar J

    2014-08-25

    Lecithin-linker microemulsions are formulations produced with soybean lecithin in combination with a highly lipophilic (lipophilic linker) and highly hydrophilic (hydrophilic linkers) surfactant-like additives. In this work, lecithin-linker systems were formulated to produce self-emulsifying delivery systems for β-carotene and β-sitosterol. The concentration of the lipophilic linker, sorbitan monooleate, was adjusted to minimize the formation of liquid crystals. The concentration of hydrophilic linkers, decaglyceryl caprylate/caprate and PEG-6-caprylic/capric glycerides, was gradually increased (scanned) until single phase clear microemulsions were obtained. For these scans, the oil (ethyl caprate) to water ratio was set to 1. The single phase, clear microemulsions were diluted with fed-state simulated intestinal fluid (FeSSIF) and produced stable emulsions, with drop sizes close to 200 nm. Using pseudo-ternary phase diagrams to evaluate the process of dilution of microemulsion preconcentrates (mixtures of oil, lecithin and linkers with little or no water) with FeSSIF, it was determined that self-emulsifying systems are obtained when the early stages of the dilution produce single phase microemulsions. If liquid crystals or multiple phase systems are obtained during those early stages, then the emulsification yields unstable emulsions with large drop sizes. An in vitro permeability study conducted using a Flow-Thru Dialyzer revealed that stable emulsions with drop sizes of 150-300 nm produce large and irreversible permeation of β-carotene to sheep intestine. On the other hand, unstable emulsions produced without the linker combination separated in the dialyzer chamber. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Novel Concepts of MS-Cleavable Cross-linkers for Improved Peptide Structure Analysis

    NASA Astrophysics Data System (ADS)

    Hage, Christoph; Falvo, Francesco; Schäfer, Mathias; Sinz, Andrea

    2017-06-01

    The chemical cross-linking/mass spectrometry (MS) approach is gaining increasing importance as an alternative method for studying protein conformation and for deciphering protein interaction networks. This study is part of our ongoing efforts to develop innovative cross-linking principles for a facile and efficient assignment of cross-linked products. We evaluate two homobifunctional, amine-reactive, and MS-cleavable cross-linkers regarding their potential for automated analysis of cross-linked products. We introduce the bromine phenylurea (BrPU) linker that possesses a unique structure yielding a distinctive fragmentation pattern on collisional activation. Moreover, BrPU delivers the characteristic bromine isotope pattern and mass defect for all cross-linker-decorated fragments. We compare the fragmentation behavior of the BrPU linker with that of our previously described MS-cleavable TEMPO-Bz linker (which consists of a 2,2,6,6-tetramethylpiperidine-1-oxy moiety connected to a benzyl group) that was developed to perform free-radical-initiated peptide sequencing. Comparative collisional activation experiments (collision-induced dissociation and higher-energy collision-induced dissociation) with both cross-linkers were conducted in negative electrospray ionization mode with an Orbitrap Fusion mass spectrometer using five model peptides. As hypothesized in a previous study, the presence of a cross-linked N-terminal aspartic acid residue seems to be the prerequisite for the loss of an intact peptide from the cross-linked products. As the BrPU linker combines a characteristic mass shift with an isotope signature, it presents a more favorable combination for automated assignment of cross-linked products compared with the TEMPO-Bz linker.

  1. A dimethacrylate cross-linker cleavable under thermolysis or alkaline hydrolysis conditions: synthesis, polymerization, and degradation.

    PubMed

    Elladiou, Marios; Patrickios, Costas S

    2016-02-21

    We develop a new platform based on 2,6-pyridinediethanol diesters for introducing polymer degradability under thermolysis or alkaline hydrolysis conditions, with the latter being rare in polymers. Such labile diesters can be cross-linkers, bifunctional initiators and inimers. We demonstrate the power of this platform through the synthesis of the 2,6-pyridinediethanol dimethacrylate cross-linker, its controlled (co)polymerization, and the thermal and hydrolytic cleavage of its (co)polymers.

  2. 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.

  3. Open and Closed: The Roles of Linker Histones in Plants and Animals

    PubMed Central

    Michaels, Scott D.

    2014-01-01

    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. PMID:24270504

  4. 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

  5. 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.

  6. 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

  7. Major substructure in the M31 Outer Halo: the East Cloud

    NASA Astrophysics Data System (ADS)

    McMonigal, B.; Bate, N. F.; Conn, A. R.; Mackey, A. D.; Lewis, G. F.; Irwin, M. J.; Martin, N. F.; McConnachie, A. W.; Ferguson, A. M. N.; Ibata, R. A.; Huxor, A. P.

    2016-02-01

    We present the first detailed analysis of the East Cloud, a highly disrupted diffuse stellar substructure in the outer halo of M31. The core of the substructure lies at a projected distance of ˜100 kpc from the centre of M31 in the outer halo, with possible extensions reaching right into the inner halo. Using Pan-Andromeda Archaeological Survey photometry of red giant branch stars, we measure the distance, metallicity and brightness of the cloud. Using Hubble Space Telescope data, we independently measure the distance and metallicity to the two globular clusters coincident with the East Cloud core, PA-57 and PA-58, and find their distances to be consistent with the cloud. Four further globular clusters coincident with the substructure extensions are identified as potentially associated. Combining the analyses, we determine a distance to the cloud of 814^{+20}_{-9} kpc, a metallicity of [Fe/H] = -1.2 ± 0.1, and a brightness of MV = -10.7 ± 0.4 mag. Even allowing for the inclusion of the potential extensions, this accounts for less than 20 per cent of the progenitor luminosity implied by the luminosity-metallicity relation. Using the updated techniques developed for this analysis, we also refine our estimates of the distance and brightness of the South-West Cloud, a separate substructure analysed in the previous work in this series.

  8. Morality as the Substructure of Social Justice: Religion in Education as a Case in Point

    ERIC Educational Resources Information Center

    Potgieter, Ferdinand J.

    2011-01-01

    Moral issues and principles do not only emerge in cases of conflict among, for instance, religious communities or political parties; indeed they form the moral substructure of notions of social justice. During periods of conflict each opponent claims justice for his/her side and bases the claim on certain principles. In this article, reference is…

  9. Modal Substructuring of Geometrically Nonlinear Finite Element Models with Interface Reduction

    DOE PAGES

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

    2017-03-29

    Substructuring methods have been widely used in structural dynamics to divide large, complicated finite element models into smaller substructures. For linear systems, many methods have been developed to reduce the subcomponents down to a low order set of equations using a special set of component modes, and these are then assembled to approximate the dynamics of a large scale model. In this paper, a substructuring approach is developed for coupling geometrically nonlinear structures, where each subcomponent is drastically reduced to a low order set of nonlinear equations using a truncated set of fixedinterface and characteristic constraint modes. The method usedmore » to extract the coefficients of the nonlinear reduced order model (NLROM) is non-intrusive in that it does not require any modification to the commercial FEA code, but computes the NLROM from the results of several nonlinear static analyses. The NLROMs are then assembled to approximate the nonlinear differential equations of the global assembly. The method is demonstrated on the coupling of two geometrically nonlinear plates with simple supports at all edges. The plates are joined at a continuous interface through the rotational degrees-of-freedom (DOF), and the nonlinear normal modes (NNMs) of the assembled equations are computed to validate the models. The proposed substructuring approach reduces a 12,861 DOF nonlinear finite element model down to only 23 DOF, while still accurately reproducing the first three NNMs of the full order model.« less

  10. 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.

  11. 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.

  12. 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)

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. Evolution of Dislocation Substructures in Nickel Single Crystals and Deformation Mechanisms

    NASA Astrophysics Data System (ADS)

    Solov'ev, A. N.; Starenchenko, S. V.; Solov'eva, Yu. V.

    2017-08-01

    The stress-strain curve for Ni single crystals with the [100] compression axis is investigated and the deformation relief and the dislocation structure are studied. It is established that the stages of strain hardening of the single crystals correspond to the formed deformation relief and to predominantly observed dislocation substructure.

  18. Loop substructure identification for shear structures of unknown structural mass using synthesized references

    NASA Astrophysics Data System (ADS)

    Zhang, Dongyu; Li, Hui

    2017-08-01

    Shear structure is widely adopted to model the dynamics for building structures. Thus, developing accurate and efficient parameter identification methods for a shear structure plays a crucial role in structural health monitoring for building structures. In the authors’ previous studies, a loop substructure identification (LSI) method was proposed for shear structures, in which the dynamic equation of a two-story substructure is utilized to establish a loop identification sequence, directly estimating the substructure’s parameters. To ensure the convergence of the loop identification sequence, some structural control (SC) systems are needed to change the critical structural responses in a favorable way. However, the limited availability of SC systems in general buildings restrains the wide application of this controlled loop substructure identification (CLSI) method. In this paper, the original LSI method is first reformed, which can perform the LSI even if the structural mass is unknown. Then, a new reference selection method is proposed to make the LSI method converge without the help of SC systems. Different synthesized reference responses, formed by a weighted linear combination of measured structural responses, are used to formulate the LSI sequence. Next, an optimization strategy is proposed to determine the optimal weighting factors of the synthesized reference responses, which makes the LSI converged. Finally, the LSI is carried out for a 20-story shear structure, the identification results of which show that the proposed LSI method, combined with the proposed reference selection method, can very accurately estimate the substructure parameters of the shear structure.

  19. 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…

  20. 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…

  1. Identification of population substructure among Jews using STR markers and dependence on reference populations included

    PubMed Central

    2010-01-01

    Background Detecting population substructure is a critical issue for association studies of health behaviors and other traits. Whether inherent in the population or an artifact of marker choice, determining aspects of a population's genetic history as potential sources of substructure can aid in design of future genetic studies. Jewish populations, among which association studies are often conducted, have a known history of migrations. As a necessary step in understanding population structure to conduct valid association studies of health behaviors among Israeli Jews, we investigated genetic signatures of this history and quantified substructure to facilitate future investigations of these phenotypes in this population. Results Using 32 autosomal STR markers and the program STRUCTURE, we differentiated between Ashkenazi (AJ, N = 135) and non-Ashkenazi (NAJ, N = 226) Jewish populations in the form of Northern and Southern geographic genetic components (AJ north 73%, south 23%, NAJ north 33%, south 60%). The ability to detect substructure within these closely related populations using a small STR panel was contingent on including additional samples representing major continental populations in the analyses. Conclusions Although clustering programs such as STRUCTURE are designed to assign proportions of ancestry to individuals without reference population information, when Jewish samples were analyzed in the absence of proxy parental populations, substructure within Jews was not detected. Generally, for samples with a given grandparental country of birth, STRUCTURE assignment values to Northern, Southern, African and Asian clusters agreed with mitochondrial DNA and Y-chromosomal data from previous studies as well as historical records of migration and intermarriage. PMID:20546593

  2. X-RAY SUBSTRUCTURE STUDIES OF FOUR GALAXY CLUSTERS USING XMM-NEWTON DATA

    SciTech Connect

    Zhang Yuying; Reiprich, Thomas H.; Hudson, Daniel S.; Finoguenov, Alexis; Sarazin, Craig L.

    2009-07-10

    Mahdavi et al. find that the degree of agreement between weak lensing and X-ray mass measurements is a function of cluster radius. Numerical simulations also point out that X-ray mass proxies do not work equally well at all radii. The origin of the effect is thought to be associated with cluster mergers. Recent work presenting the cluster maps showed an ability of X-ray maps to reveal and study cluster mergers in detail. Here, we present a first attempt to use the study of substructure in assessing the systematics of the hydrostatic mass measurements using two-dimensional (2D) X-ray diagnostics. The temperature map is uniquely able to identify the substructure in an almost relaxed cluster which would be unnoticed in the intracluster medium electron number density and pressure maps. We describe the radial fluctuations in the 2D maps by a cumulative/differential scatter profile relative to the mean profile within/at a given radius. The amplitude indicates {approx}10% fluctuations in the temperature, electron number density, and entropy maps, and {approx}15% fluctuations in the pressure map. The amplitude of and the discontinuity in the scatter complement 2D substructure diagnostics, e.g., indicating the most disturbed radial range. There is a tantalizing link between the substructure identified using the scatter of the entropy and pressure fluctuations and the hydrostatic mass bias relative to the expected mass based on the M-Y{sub X} and M-M{sub gas} relations particularly at r{sub 500}. XMM-Newton observations with {approx}120,000 source photons from the cluster are sufficient to apply our substructure diagnostics via the spectrally measured 2D temperature, electron number density, entropy, and pressure maps.

  3. 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.

  4. 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

  5. Modeling studies of chromatin fiber structure as a function of DNA linker length

    PubMed Central

    Perišić, Ognjen; Collepardo-Guevara, Rosana; Schlick, Tamar

    2010-01-01

    Chromatin fibers encountered in various species and tissues are characterized by different nucleosome repeat lengths (NRL) of the linker DNA connecting the nucleosomes. While single cellular organisms and rapidly growing cells with high protein production have short NRL ranging from 160 to 189 base pairs (bp), mature cells usually have longer NRL ranging between 190 and 220 bp. Recently, various experimental studies have examined the effect of NRL on the internal organization of chromatin fiber. Here we investigate by mesoscale modeling of oligonucleosomes the folding patterns for different NRL, with and without linker histone, under typical monovalent salt conditions using both one-start solenoid and two-start zigzag starting configurations. We find that short to medium NRL chromatin fibers (173 to 209 bp) with linker histone condense into irregular zigzag structures, and that solenoid-like features are viable only for longer NRL (226 bp). We suggest that medium NRL are more advantageous for packing and various levels of chromatin compaction throughout the cell cycle than their shortest and longest brethren; the former (short NRL) fold into narrow fibers, while the latter (long NRL) arrays do not easily lead to high packing ratios due to possible linker DNA bending. Moreover, we show that the linker histone has a small effect on the condensation of short-NRL arrays but an important condensation effect on medium-NRL arrays which have linker lengths similar to the linker histone lengths. Finally, we suggest that the medium-NRL species, with densely packed fiber arrangements, may be advantageous for epigenetic control because their histone tail modifications can have a greater effect compared to other fibers due to their more extensive nucleosome interaction network. PMID:20709077

  6. Galectin multimerization and lattice formation are regulated by linker region structure.

    PubMed

    Earl, Lesley A; Bi, Shuguang; Baum, Linda G

    2011-01-01

    Galectins regulate cellular functions by binding to glycan ligands on cell surface glycoprotein receptors. Prototype galectins, such as galectin-1, are one carbohydrate recognition domain (CRD) monomers that noncovalently dimerize, whereas tandem-repeat galectins, such as galectin-9, have two non-identical CRDs connected by a linker domain. Dimerization of prototype galectins, or both CRDs in tandem-repeat galectins, is typically required for the crosslinking of glycoprotein receptors and subsequent cellular signaling. Several studies have found that tandem-repeat galectins are more potent than prototype galectins in triggering many cell responses, including cell death. These differences could be due to CRD specificity, the presence or absence of a linker domain between CRDs, or both. To interrogate the basis for the increased potency of tandem-repeat galectins compared with prototype galectins in triggering cell death, we created three tandem-repeat galectin constructs with different linker regions joining identical galectin-1 CRDs, so that any differences we observed would be due to the contribution of the linker region rather than due to CRD specificity. We found that random-coil or rigid α-helical linkers that permit separation of the two galectin-1 CRDs facilitated the formation of higher-order galectin multimers and that these galectins were more potent in binding to glycan ligands and cell surface glycoprotein receptors, as well as triggering T cell death, compared with native galectin-1 or a construct with a short rigid linker. Thus, the increased potency of tandem-repeat galectins compared with prototype galectins is likely due to the ability of the linker domain to permit intermolecular CRD interactions, resulting in the formation of higher-order multimers with increased valency, rather than differences in CRD specificity.

  7. Galectin multimerization and lattice formation are regulated by linker region structure

    PubMed Central

    Earl, Lesley A; Bi, Shuguang; Baum, Linda G

    2011-01-01

    Galectins regulate cellular functions by binding to glycan ligands on cell surface glycoprotein receptors. Prototype galectins, such as galectin-1, are one carbohydrate recognition domain (CRD) monomers that noncovalently dimerize, whereas tandem-repeat galectins, such as galectin-9, have two non-identical CRDs connected by a linker domain. Dimerization of prototype galectins, or both CRDs in tandem-repeat galectins, is typically required for the crosslinking of glycoprotein receptors and subsequent cellular signaling. Several studies have found that tandem-repeat galectins are more potent than prototype galectins in triggering many cell responses, including cell death. These differences could be due to CRD specificity, the presence or absence of a linker domain between CRDs, or both. To interrogate the basis for the increased potency of tandem-repeat galectins compared with prototype galectins in triggering cell death, we created three tandem-repeat galectin constructs with different linker regions joining identical galectin-1 CRDs, so that any differences we observed would be due to the contribution of the linker region rather than due to CRD specificity. We found that random-coil or rigid α-helical linkers that permit separation of the two galectin-1 CRDs facilitated the formation of higher-order galectin multimers and that these galectins were more potent in binding to glycan ligands and cell surface glycoprotein receptors, as well as triggering T cell death, compared with native galectin-1 or a construct with a short rigid linker. Thus, the increased potency of tandem-repeat galectins compared with prototype galectins is likely due to the ability of the linker domain to permit intermolecular CRD interactions, resulting in the formation of higher-order multimers with increased valency, rather than differences in CRD specificity. PMID:20864568

  8. 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.

  9. 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.

  10. The Role of Linkers in the Excited-State Dynamic Planarization Processes of Macrocyclic Oligothiophene 12-Mers.

    PubMed

    Kim, Woojae; Sung, Jooyoung; Park, Kyu Hyung; Shimizu, Hideyuki; Imamura, Mika; Han, Minwoo; Sim, Eunji; Iyoda, Masahiko; Kim, Dongho

    2015-11-05

    Linkers adjoining chromophores play an important role in modulating the structure of conjugated systems, which is bound up with their photophysical properties. However, to date, the focus of works dealing with linker effects was limited only to linear π-conjugated materials, and there have been no detailed studies on cyclic counterparts. Herein we report the linker effects on the dynamic planarization processes of π-conjugated macrocyclic oligothiophene 12-mers, where the different ratio between ethynylene and vinylene linkers was chosen to control the backbone rigidity. By analyzing transient fluorescence spectra, we demonstrate that the connecting linkers play a crucial role in the excited-state dynamics of cyclic conjugated systems. Faster dynamic planarization, longer exciton delocalization length, and higher degree of planarity were observed in vinylene inserted cyclic oligothiophenes. Molecular dynamics simulations and density functional theory calculations also stress the importance of the role of linkers in modulating the structure of cyclic oligothiophenes.

  11. 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

  12. 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

  13. 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

  14. 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

  15. Dynamic condensation of linker histone C-terminal domain regulates chromatin structure.

    PubMed

    Luque, Antoni; Collepardo-Guevara, Rosana; Grigoryev, Sergei; Schlick, Tamar

    2014-07-01

    The basic and intrinsically disordered C-terminal domain (CTD) of the linker histone (LH) is essential for chromatin compaction. However, its conformation upon nucleosome binding and its impact on chromatin organization remain unknown. Our mesoscale chromatin model with a flexible LH CTD captures a dynamic, salt-dependent condensation mechanism driven by charge neutralization between the LH and linker DNA. Namely, at low salt concentration, CTD condenses, but LH only interacts with the nucleosome and one linker DNA, resulting in a semi-open nucleosome configuration; at higher salt, LH interacts with the nucleosome and two linker DNAs, promoting stem formation and chromatin compaction. CTD charge reduction unfolds the domain and decondenses chromatin, a mechanism in consonance with reduced counterion screening in vitro and phosphorylated LH in vivo. Divalent ions counteract this decondensation effect by maintaining nucleosome stems and expelling the CTDs to the fiber exterior. Additionally, we explain that the CTD folding depends on the chromatin fiber size, and we show that the asymmetric structure of the LH globular head is responsible for the uneven interaction observed between the LH and the linker DNAs. All these mechanisms may impact epigenetic regulation and higher levels of chromatin folding. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. A Fluorous-Tagged Linker from Which Small Molecules Are Released by Ring-Closing Metathesis

    PubMed Central

    Leach, Stuart G.; Cordier, Christopher J.; Morton, Daniel; McKiernan, Gordon J.; Warriner, Stuart; Nelson, Adam

    2008-01-01

    A fluorous-tagged linker for the parallel synthesis of small- and medium-ring and macrocyclic nitrogen heterocycles using ring-closing metathesis is described. The linker was designed such that “cyclization-release” of the cyclic heterocyclic products was coupled with liberation of the active catalyst. The design of the linker was validated using a non-fluorous-tagged model. A wide range of unsaturated alcohols were used as reagents to functionalize a fluorous-tagged sulfonamide,(Z)-{N-[4-(2-(N’-3,3,4,4,5,5,6,6,7,7,8,8,9,9,-10,10,10-heptadecafluorodecyl)-4-methylsulfonamido)methylallyloxy]but-2-enyl}-2-nitrobenzene-sulfonamide, using Fukuyama-Mitsunobu reactions; in each case, fluorous-solid-phase extraction (F-SPE) was used to purify the functionalized linker from the excess reagents. In general, the “cyclization-release” of cyclic products was triggered using a light-fluorous tagged derivative of the Grubbs-Hoveyda second-generation catalyst. After the metathesis step, F-SPE was used to purify released cyclic compounds from the fluorous-tagged linker and the fluorous-tagged catalyst. The scope and limitations of the approach were determined using a range of substrates which probed different aspects of the functionalization and metathesis steps. In the study as a whole, a wide range of small- and medium-ring and macrocyclic nitrogen heterocycles were prepared using polyene and polyenyne metathesis cascades. PMID:18327951

  17. 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.

  18. EGFP-Tagged Core and Linker Histones Diffuse via Distinct Mechanisms within Living Cells

    PubMed Central

    Bhattacharya, Dipanjan; Mazumder, Aprotim; Miriam, S. Annie; Shivashankar, G. V.

    2006-01-01

    The effect of chromatin organization on EGFP-tagged histone protein dynamics within the cell nucleus has been probed using fluorescence correlation and recovery measurements on single living HeLa cells. Our studies reveal that free fraction of core-particle histones exist as multimers within the cell nucleus whereas the linker histones exist in monomeric forms. The multimeric state of core histones is found to be invariant across mammalian and polytene chromosomes and this is ATP dependent. In contrast, the dynamics of the linker histones exhibits two distinct diffusion timescales corresponding to its transient binding and unbinding to chromatin governed by the tail domain residues. Under conditions of chromatin condensation induced by apoptosis, the free multimeric fraction of core histones is found to become immobile, while the monomeric linker histone mobility is partially reduced. In addition, we observe differences in nuclear colocalization of linker and core particle histones. These results are validated through Brownian dynamics simulation of core and linker histone mobility. Our findings provide a framework to understand the coupling between the state of chromatin assembly and histone protein dynamics that is central to accessing regulatory sites on the genome. PMID:16815908

  19. 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.

  20. 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.

  1. Conformational selection and dynamic adaptation upon linker histone binding to the nucleosome.

    PubMed

    Öztürk, Mehmet Ali; Pachov, Georgi V; Wade, Rebecca C; Cojocaru, Vlad

    2016-08-19

    Linker histones are essential for DNA compaction in chromatin. They bind to nucleosomes in a 1:1 ratio forming chromatosomes. Alternative configurations have been proposed in which the globular domain of the linker histone H5 (gH5) is positioned either on- or off-dyad between the nucleosomal and linker DNAs. However, the dynamic pathways of chromatosome assembly remain elusive. Here, we studied the conformational plasticity of gH5 in unbound and off-dyad nucleosome-bound forms with classical and accelerated molecular dynamics simulations. We find that the unbound gH5 converts between open and closed conformations, preferring the closed form. However, the open gH5 contributes to a more rigid chromatosome and restricts the motion of the nearby linker DNA through hydrophobic interactions with thymidines. Moreover, the closed gH5 opens and reorients in accelerated simulations of the chromatosome. Brownian dynamics simulations of chromatosome assembly, accounting for a range of amplitudes of nucleosome opening and different nucleosome DNA sequences, support the existence of both on- and off-dyad binding modes of gH5 and reveal alternative, sequence and conformation-dependent chromatosome configurations. Taken together, these findings suggest that the conformational dynamics of linker histones and nucleosomes facilitate alternative chromatosome configurations through an interplay between induced fit and conformational selection. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. 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.

  3. 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.

  4. 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

  5. Top-down synthesis of versatile polyaspartamide linkers for single-step protein conjugation to materials.

    PubMed

    Cha, Chaenyung; Jeong, Jae Hyun; Tang, Xin; Zill, Andrew T; Prakash, Y S; Zimmerman, Steven C; Saif, Taher A; Kong, Hyunjoon

    2011-12-21

    Materials used in various biological applications are often modified with proteins to regulate biomolecular and cellular adhesion. Conventional strategies of protein conjugation accompany monovalent bifunctional protein linkers, which present several limitations in molecular synthesis and protein conjugation. Herein, we present a new strategy of preparing multivalent polyaspartamide linkers in a simple top-down manner, and also demonstrate that the resulting polymer linkers allow us to readily conjugate proteins to both organic and inorganic materials. The top-down synthesis of polyaspartamide linkers was performed by partially opening succinimidyl ring moieties of polysuccinimide (PSI) with the controlled number of nucleophiles reactive to photo-cross-linked hydrogel or gold-coated inorganic materials: (1) Poly(2-hydroxyethyl-co-2-methacryloxyethyl aspartamide) (PHMAA) presenting methacrylate was used to micropattern fibronectin or collagen on a hydrogel in order to regulate cell adhesion and growth area on a micrometer scale. (2) Poly(2-hydroxyethyl-co-2-mercaptoethyl aspartamide) (PHMCA) presenting thiol functional groups was used to link fibronectin to a gold-coated silicon microelectromechanical probe designed to measure cell traction force. Overall, these multivalent polyaspartamide protein linkers will greatly assist efforts to analyze and regulate the cellular adhesion to and phenotypic activities of a wide array of substrates and devices.

  6. Conformational selection and dynamic adaptation upon linker histone binding to the nucleosome

    PubMed Central

    Öztürk, Mehmet Ali; Pachov, Georgi V.; Wade, Rebecca C.; Cojocaru, Vlad

    2016-01-01

    Linker histones are essential for DNA compaction in chromatin. They bind to nucleosomes in a 1:1 ratio forming chromatosomes. Alternative configurations have been proposed in which the globular domain of the linker histone H5 (gH5) is positioned either on- or off-dyad between the nucleosomal and linker DNAs. However, the dynamic pathways of chromatosome assembly remain elusive. Here, we studied the conformational plasticity of gH5 in unbound and off-dyad nucleosome-bound forms with classical and accelerated molecular dynamics simulations. We find that the unbound gH5 converts between open and closed conformations, preferring the closed form. However, the open gH5 contributes to a more rigid chromatosome and restricts the motion of the nearby linker DNA through hydrophobic interactions with thymidines. Moreover, the closed gH5 opens and reorients in accelerated simulations of the chromatosome. Brownian dynamics simulations of chromatosome assembly, accounting for a range of amplitudes of nucleosome opening and different nucleosome DNA sequences, support the existence of both on- and off-dyad binding modes of gH5 and reveal alternative, sequence and conformation-dependent chromatosome configurations. Taken together, these findings suggest that the conformational dynamics of linker histones and nucleosomes facilitate alternative chromatosome configurations through an interplay between induced fit and conformational selection. PMID:27270081

  7. 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

  8. 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

  9. A role in DNA binding for the linker sequences of the first three zinc fingers of TFIIIA.

    PubMed Central

    Choo, Y; Klug, A

    1993-01-01

    Zinc fingers of the TFIIIA type are connected by short linker sequences between the structural units. Structural investigations by 2D NMR in solution and by X-ray crystallographic analyses of complexes with DNA point to a passive role for the linkers. We have therefore investigated the influence of the linker sequence on DNA binding using as a model the first three fingers of the protein TFIIIA. Insertion of certain heterologous linkers abolishes binding, and replacement of individual amino acids can reduce binding by factors of up to twenty-four. Images PMID:8346014

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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)

  16. 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.

  17. 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.

  18. Cellular organization and substructure measured using angle-resolved low-coherence interferometry.

    PubMed Central

    Wax, Adam; Yang, Changhuei; Backman, Vadim; Badizadegan, Kamran; Boone, Charles W; Dasari, Ramachandra R; Feld, Michael S

    2002-01-01

    We measure the organization and substructure of HT29 epithelial cells in a monolayer using angle-resolved low-coherence interferometry. This new technique probes cellular structure by measuring scattered light, as in flow cytometry, but offers an advantage in that the structure can be examined in situ, avoiding the need to disrupt the cell monolayer. We determine the size distribution of the cell nuclei by fitting measured light-scattering spectra to the predictions of Mie theory. In addition, we obtain information about the cellular organization and substructure by examining the spatial correlations within the monolayer. A remarkable finding is that the spatial correlations over small length scales take the form of an inverse power law, indicating the fractal nature of the packing of the subcellular structures. We also identify spatial correlations on a scale large compared with the size of a cell, indicating an overlying order within the monolayer. PMID:11916880

  19. 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.

  20. Programming substructure computations for elliptic problems on the CHiP system

    NASA Technical Reports Server (NTRS)

    Gannon, D.; Snyder, L.; Van Rosendale, J.

    1983-01-01

    A number of studies have been conducted with the aim to apply parallel computation to problems associated with solving finite element equations arising in structural mechanics and fluid dynamics. These studies have provided many important results. The present investigation is concerned with a set of experiments designed to test two ideas, including configurability and substructuring. The considered algorithms and tests are intended for implementation on the Configurable, Highly Parallel (CHiP) family of architecture described by Snyder (1982). The ChiP computer is composed of homogeneous processing elements (PEs) placed at regular intervals in a lattice of programmable switches. Two examples of the role of configurability and substructuring for simple iterative algorithms are considered, giving attention to conjugate gradient iterations, and tridiagonal systems of equations.

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. The Effects of Substructure on Dynamical Studies of Galaxy Clusters

    NASA Astrophysics Data System (ADS)

    Bird, Christina M.

    1994-12-01

    Ongoing optical and X-ray studies of clusters of galaxies reveal that deviations from a smooth, relaxed distribution of galaxies and gas are common, if not ubiquitous. The claim has been made that in most cases, the ``contaminating'' structures are only a small fraction of the total mass of the system, and therefore that their effect on dynamical analyses can be ignored. In this poster I will demonstrate that even when the contaminating subclusters are low mass (and unlikely to have a significant effect on the overall cluster gravitational potential), their presence can greatly modify kinematic and dynamical quantities, such as the velocity dispersion and projected mass estimator. In addition I present distributions of velocity dispersion and dynamical masses for clusters which possess central dominant galaxies, and a re-evaluation of the velocity dispersion-temperature correlation based on this dataset.

  11. Linker design for the modular assembly of multifunctional and targeted platinum(ii)-containing anticancer agents.

    PubMed

    Ding, S; Bierbach, U

    2016-08-16

    A versatile and efficient modular synthetic platform was developed for assembling multifunctional conjugates and targeted forms of platinum-(benz)acridines, a class of highly cytotoxic DNA-targeted hybrid agents. The synthetic strategy involved amide coupling between succinyl ester-modified platinum compounds (P1, P2) and a set of 11 biologically relevant primary and secondary amines (N1-N11). To demonstrate the feasibility and versatility of the approach, a structurally and functionally diverse range of amines was introduced. These include biologically active molecules, such as rucaparib (a PARP inhibitor), E/Z-endoxifen (an estrogen receptor antagonist), and a quinazoline-based tyrosine kinase inhibitor. Micro-scale reactions in Eppendorf tubes or on 96-well plates were used to screen for optimal coupling conditions in DMF solution with carbodiimide-, uronium-, and phosphonium-based compounds, as well as other common coupling reagents. Reactions with the phosphonium-based coupling reagent PyBOP produced the highest yields and gave the cleanest conversions. Furthermore, it was demonstrated that the chemistry can also be performed in aqueous media and is amenable to parallel synthesis based on multiple consecutive reactions in DMF in a "one-tube" format. In-line LC-MS was used to assess the stability of the conjugates in physiologically relevant buffers. Hydrolysis of the conjugates occurs at the ester moiety and is facilitated by the aquated metal moiety under low-chloride ion conditions. The rate of ester cleavage greatly depends on the nature of the amine component. Potential applications of the linker technology are discussed.

  12. Comparison of Shade of Ceramic with Three Different Zirconia Substructures using Spectrophotometer.

    PubMed

    Habib, Syed Rashid; Shiddi, Ibraheem F Al

    2015-02-01

    This study assessed how changing the Zirconia (Zr) substructure affected the color samples after they have been overlaid by the same shade of veneering ceramic. Three commercial Zr materials were tested in this study: Prettau(®) Zirconia (ZirKonZahn, Italy), Cercon (Dentsply, Germany) and InCoris ZI (Sirona, Germany). For each system, 15 disk-shaped specimens (10 × 1 mm) were fabricated. Three shades of A1, A2 and A3.5 of porcelain (IPS e.MaxCeram, IvoclarVivadent, USA) were used for layering the specimens. Five specimens from each type of Zr were layered with same shade of ceramic. Color measurements were recorderd by a spectrophotometer Color-Eye(®) 7000A (X-Rite, Grand Rapids, MI). Mean values of L, a, b color coordinates and ΔE were recorded and comparisons were made. Differences in the ΔE were recorded for the same porcelain shade with different Zr substructures and affected the color of the specimens (p < 0.01, ANOVA). The maximum difference between the ΔE values for the A1, A2 and A3.5 shades with three types of Zr substructures was found to be 1.59, 1.69 and 1.45 respectively. Multiple comparisons of the ΔE with PostHoc Tukey test revealed a statistically significant difference (p < 0.05) between the three types of Zr, except between Type 2 Zr and Type 3 Zr for the Shade A1. The mean values of L, a, b and ΔE for the Prettau(®) Zirconia substructure were found to be the least among the three types. The brand of Zr used influences the final color of the all ceramic Zr based restorations and this has clinical significance.

  13. 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.

  14. The evolution of the deformation substructure in a Ni-Co-Cr equiatomic solid solution alloy

    DOE PAGES

    Miao, Jiashi; Slone, C. E.; Smith, T. M.; ...

    2017-05-15

    The equiatomic NiCoCr alloy exhibits an excellent combination of strength and ductility, even greater than the FeNiCrCoMn high entropy alloy, and also displays a simultaneous increase in strength and ductility with decreasing the testing temperature. To systemically investigate the origin of the exceptional properties of NiCoCr alloy, which are related to the evolution of the deformation substructure with strain, interrupted tensile testing was conducted on the equiatomic NiCoCr single-phase solid solution alloy at both cryogenic and room temperatures at five different plastic strain levels of 1.5%, 6.5%, 29%, 50% and 70%. The evolution of deformation substructure was examined using electronmore » backscatter diffraction (EBSD), transmission Kikuchi diffraction (TKD), conventional transmission electron microscopy (CTEM), diffraction contrast imaging using STEM (DCI-STEM) and atomic resolution scanning transmission electron microscopy. While the deformation substructure mainly consisted of planar dislocation slip and the dissociation of dislocations into stacking faults at small strain levels (≤6.5%), at larger strain levels, additional substructures including nanotwins and a new phase with hexagonal close packed (HCP) lamellae also appeared. The volume fraction of the HCP lamellae increases with increasing deformation, especially at cryogenic temperature. First principles calculations at 0 K indicate that the HCP phase is indeed energetically favorable relative to FCC for this composition. In conclusion, the effects of the nanotwin and HCP lamellar structures on hardening rate and ductility at both cryogenic and room temperature are qualitatively discussed.« less

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. On the Shock Stress, Substructure Evolution, and Spall Response of Commercially Pure 1100-O Aluminum

    DTIC Science & Technology

    2014-12-01

    recovery experiments were conducted at shock stresses of approxi- mately 4 , 6 , and 9 GPa to study the substructure evolution, while spall recovery...experiments were conducted at shock stresses of approximately 6 and 9 GPa to study the spall fracture surfaces. As shown in Fig. 3, a 4 mm thick by 30 mm...different voltages ranging from 6 –60 V in a TenuPol-3 digitally controlled automatic electropolisher . The hardness of the recovered samples was measured

  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. SIRS-SS: a system for simulating IR/Raman spectra. 1. Substructure/subspectrum correlation.

    PubMed

    Yao, J; Fan, B; Doucet, J P; Panaye, A; Yuan, S; Li, J

    2001-01-01

    An IR/RAMAN spectra simulation system is reported. The development of this software was based on the substructure/subspectrum relationships established for four different structural classes: small molecules, special fragments, atom-centered FRELs, and bond-centered FRELs (FREL: Fragment centered on an Environment which is Limited). Four corresponding knowledge-bases (now, at a pilot stage) are constructed from usual correlation charts or data analyses of large populations of compounds using data mining techniques.

  2. 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 ...

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. Absence of glycosylation on cyanobacterial phycobilisome linker polypeptides and rhodophytan phycoerythrins.

    PubMed Central

    Fairchild, C D; Jones, I K; Glazer, A N

    1991-01-01

    The 27-, 30-, and 33-kDa rod linker polypeptides and the 75-kDa core linker of phycobilisomes from the cyanobacterium Synechococcus sp. strain PCC 7942 have been reported to be glycoproteins with carbohydrate contents ranging from 3.2 to 18.8% and composed of N-acetylgalactosamine and glucose (H.C. Riethman, T.P. Mawhinney, and L.A. Sherman, J. Bacteriol. 170:2433-2440, 1988). Synechococcus sp. strain PCC 7942 phycobilisomes were purified extensively, and the linker polypeptides were separated from the phycobiliproteins by precipitation in 1 M NaSCN. Upon hydrolysis, the linker fraction yielded 0.037% glucose and 0.015% galactosamine by weight and no other carbohydrate. Phycobilisome polypeptides separated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate were subjected to various glycoprotein-specific staining procedures. Linker polypeptides showed very weak concanavalin A binding and no staining by the Schiff-periodate method or by a much more sensitive periodate oxidation-based method. These results indicated that the linker polypeptides are not glycosylated. An earlier report (T. Fujiwara, J. Biochem. 49:361-367, 1961) contended, on the basis of the isolation of sugar-containing peptic chromopeptides from Porphyra tenera R-phycoerythrin, that this red algal phycobiliprotein is a glycoprotein. Analysis of Gastroclonium coulteri R-phycoerythrin and Porphyridium cruentum B-phycoerythrin revealed only traces of carbohydrate in these two proteins, 0.36 and 0.14%, respectively. Results of glycoprotein staining of gels suggested that the carbohydrate in the R-phycoerythrin preparation is due to a glycoprotein contaminant and that neither red algal phycoerythrin is glycosylated. Images PMID:1902214

  9. Analysis and inverse substructuring computation on dynamic quality of mechanical assembly

    NASA Astrophysics Data System (ADS)

    Lü, Guangqing; Yi, Chuijie; Fang, Ke

    2016-05-01

    Mechanical assembly has its own dynamic quality directly affecting the dynamic quality of whole product and should be considered in quality inspection and estimation of mechanical assembly. Based on functional relations between dynamic characteristics involved in mechanical assembly, the effects of assembling process on dynamic characteristics of substructural components of an assembly system are investigated by substructuring analysis. Assembly-coupling dynamic stiffness is clarified as the dominant factor of the effects and can be used as a quantitative measure of assembly dynamic quality. Two computational schemes using frequency response functions(FRFs) to determine the stiffness are provided and discussed by inverse substructuring analysis, including their applicable conditions and implementation procedure in application. Eigenvalue analysis on matrix-ratios of FRFs before and after assembling is employed and well validates the analytical outcomes and the schemes via both a lumped-parameter model and its analogic experimental counterpart. Applying the two schemes to inspect the dynamic quality provides the message of dynamic performance of the assembly system, and therefore improves conventional quality inspection and estimation of mechanical assembly in completeness.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Fiber-reinforced composite substructure: load-bearing capacity of an onlay restoration.

    PubMed

    Garoushi, Sufyan K; Lassila, Lippo V J; Vallittu, Pekka K

    2006-10-01

    To determine the static load-bearing capacity of composite resin onlay restorations made of particulate filler composite (PFC) with two different types of fiber-reinforced composite (FRC) substructures. Specimens were prepared to simulate an onlay restoration, composed of a 2 to 3 mm FRC layer as the substructure (short random and continuous bidirectional fiber orientation) and a 1 mm surface layer of PFC. Control specimens were prepared from plain PFC. The specimens were incrementally polymerized with a hand-light curing unit for 40 s and then post-cured in a light-curing oven for 15 min. The specimens were cemented on dentin substrate of extracted human molars using a standard adhesive resin cementation technique. The specimens (n=8/group) were water stored either for 24 h at room temperature or for 4 weeks at 37 degrees C before they were statically loaded until fracture using a universal testing machine. Failure modes were visually examined. ANOVA revealed that all specimens with FRC substructures had higher values of static load-bearing capacity than those obtained with plain PFC (p<0.001). The load-bearing capacity of all the specimens decreased after water storage (p<0.001). Restorations made from a combination of FRC and PFC showed better load-bearing capacity than those obtained with PFC alone.

  19. Development of a standardized method for contouring the larynx and its substructures.

    PubMed

    Choi, Mehee; Refaat, Tamer; Lester, Malisa S; Bacchus, Ian; Rademaker, Alfred W; Mittal, Bharat B

    2014-12-11

    Limiting radiation dose to the larynx can diminish effects of laryngeal dysfunction. However, no clear guidelines exist for defining the larynx and its substructures consistently on cross-sectional imaging. This study presents computed tomography (CT)- and magnetic resonance imaging (MRI)-based guidelines for contouring laryngeal organs-at-risk (OARs). Standardized guidelines for delineating laryngeal OARs were devised and used to delineate on CT and MRI for head-and-neck cancer patients. Volumetric comparisons were performed to evaluate consistency and reproducibility of guideline-based contours. For the initial 5 patients the mean CT and MRI based larynx volume did not differ significantly between imaging modalities; 34.39 ± 9.85 vs. 35.01 ± 9.47 (p = .09). There was no statistical difference between the CT based mean laryngeal volume in the subsequent 44 patients compared to the initial 5 patients outlined on CT and the MRI scan (p = 0.53 and 0.62). The OAR volume for laryngeal substructures were not statistically different among patients or between imaging modalities. Once established, the guidelines were easy to follow. The guidelines developed provide a precise method for delineating laryngeal OARs. These guidelines need to be validated and clinical significance of outlining laryngeal substructures and dose-volume constraints should be investigated before routine implementation in clinic practice.

  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. 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

  3. 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.

  4. 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.

  5. 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.

  6. Detailed Mutational Analysis of Vga(A) Interdomain Linker: Implication for Antibiotic Resistance Specificity and Mechanism

    PubMed Central

    Lenart, Jakub; Vimberg, Vladimir; Vesela, Ludmila; Janata, Jiri

    2014-01-01

    Detailed mutational analysis examines the roles of individual residues of the Vga(A) linker in determining the antibiotic resistance phenotype. It defines a narrowed region of residues 212 to 220 whose composition determines the resistance specificity to lincosamides, pleuromutilins, and/or streptogramins A. From the analogy with the recently described function of the homologous ABC-F protein EttA as a translational factor, we infer that the Vga(A) linker interacts with the ribosome and directly or indirectly affects the binding of the respective antibiotic. PMID:25512423

  7. 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

  8. 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.'

  9. 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.'

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. The effect of translucency of Y-TZP based all-ceramic crowns fabricated with difference substructure designs.

    PubMed

    Kumagai, Naota; Hirayama, Hiroshi; Finkelman, Matthew D; Ishikawa-Nagai, Shigemi

    2013-08-01

    To analyse the effect of translucency of Y-TZP based all-ceramic crowns fabricated with different substructure thicknesses and extensions. The effect of restoration shading is also investigated. A maxillary right central incisal typodont tooth was prepared and a die was fabricated with Type IV stone after making impression. Horizontally and vertically reduced substructure extensions were designed at the facial cervical part with 0.3 mm and 0.5mm thick Lava Y-TZP. Each substructure was fabricated with two different shades, FS1 and FS7. A1 shade veneering porcelain was applied on FS1 shade Y-TZP substructures and D3 shade veneering porcelain was applied on FS7 shade Y-TZP substructures with lost wax and press ceramic technique. Ten specimens were fabricated for a total of 8 groups. The cervical and body colour of specimens were analysed with a spectrophotometer, after placing specimens on the two different coloured abutment teeth using translucent try-in cement. The data were obtained in CIELAB colour coordinates L*a*b*, and DE* through the test specimens over ND1 and ND8 shade abutments were calculated. At the cervical area, there was a significant difference on substructure extension (P < 0.001). At the body area, results were borderline on substructure thickness (P = 0.05) and there was a significant difference on restoration shade (P = 0.001). Vertical reduction design of Y-TZP substructure could increase DE* at the cervical area. Decreasing thickness of Y-TZP substructure may increase DE* at the body area. Increasing the value of Y-TZP based-all ceramic crown shade could increase DE* at the body area. The translucency of a Y-TZP based all-ceramic crowns may influence its esthetic outcome when it is used on a discoloured abutment tooth. Clinicians should be aware of the effect of substructure design on the translucency of YTZP based all-ceramic crowns. 2012 Elsevier Ltd. All rights reserved.

  15. 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

  16. Detection of Ligation Products of DNA Linkers with 5′-OH Ends by Denaturing PAGE Silver Stain

    PubMed Central

    Li, Wei; Zhang, Xuerong

    2012-01-01

    To explore if DNA linkers with 5′-hydroxyl (OH) ends could be joined by commercial T4 and E. coli DNA ligase, these linkers were synthesized by using the solid-phase phosphoramidite method and joined by using commercial T4 and E. coli DNA ligases. The ligation products were detected by using denaturing PAGE silver stain and PCR method. About 0.5–1% of linkers A–B and E–F, and 0.13–0.5% of linkers C–D could be joined by T4 DNA ligases. About 0.25–0.77% of linkers A–B and E–F, and 0.06–0.39% of linkers C–D could be joined by E. coli DNA ligases. A 1-base deletion (-G) and a 5-base deletion (-GGAGC) could be found at the ligation junctions of the linkers. But about 80% of the ligation products purified with a PCR product purification kit did not contain these base deletions, meaning that some linkers had been correctly joined by T4 and E. coli DNA ligases. In addition, about 0.025–0.1% of oligo 11 could be phosphorylated by commercial T4 DNA ligase. The phosphorylation products could be increased when the phosphorylation reaction was extended from 1 hr to 2 hrs. We speculated that perhaps the linkers with 5′-OH ends could be joined by T4 or E. coli DNA ligase in 2 different manners: (i) about 0.025–0.1% of linkers could be phosphorylated by commercial T4 DNA ligase, and then these phosphorylated linkers could be joined to the 3′-OH ends of other linkers; and (ii) the linkers could delete one or more nucleotide(s) at their 5′-ends and thereby generated some 5′-phosphate ends, and then these 5′-phosphate ends could be joined to the 3′-OH ends of other linkers at a low efficiency. Our findings may probably indicate that some DNA nicks with 5′-OH ends can be joined by commercial T4 or E. coli DNA ligase even in the absence of PNK. PMID:22761747

  17. 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.

  18. Directly labeled DNA probes using fluorescent nucleotides with different length linkers.

    PubMed Central

    Zhu, Z; Chao, J; Yu, H; Waggoner, A S

    1994-01-01

    Directly labeled fluorescent DNA probes have been made by nick translation and PCR using dUTP attached to the fluorescent label, Cy3, with different length linkers. With preparation of probes by PCR we find that linker length affects the efficiency of incorporation of Cy3-dUTP, the yield of labeled probe, and the signal intensity of labeled probes hybridized to chromosome target sequences. For nick translation and PCR, both the level of incorporation and the hybridization fluorescence signal increased in parallel when the length of the linker arm is increased. Under optimal conditions, PCR yielded more densely labeled probes, however, the yield of PCR labeled probe decreased with greater linear density of labeling. By using a Cy3-modified dUTP with the longest linker under optimal conditions it was possible to label up to 28% of the possible substitution sites on the target DNA with reasonable yield by PCR and 18% by nick translation. A mechanism involving steric interactions between the polymerase, cyanine-labeled sites on template and extending chains and the modified dUTP substrate is proposed to explain the inverse correlation between the labeling efficiency and the yield of DNA probe synthesis by PCR. Images PMID:8078779

  19. 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…

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. Antibody drug conjugates: design and selection of linker, payload and conjugation chemistry.

    PubMed

    McCombs, Jessica R; Owen, Shawn C

    2015-03-01

    Antibody drug conjugates (ADCs) have emerged as an important pharmaceutical class of drugs designed to harness the specificity of antibodies with the potency of small molecule therapeutics. The three main components of ADCs are the antibody, the linker, and the payload; the majority of early work focused intensely on improving the functionality of these pieces. Recently, considerable attention has been focused on developing methods to control the site and number of linker/drug conjugated to the antibody, with the aim of producing more homogenous ADCs. In this article, we review popular conjugation methods and highlight recent approaches including "click" conjugation and enzymatic ligation. We discuss current linker technology, contrasting the characteristics of cleavable and non-cleavable linkers, and summarize the essential properties of ADC payload, centering on chemotherapeutics. In addition, we report on the progress in characterizing to determine physicochemical properties and on advances in purifying to obtain homogenous products. Establishing a set of selection and analytical criteria will facilitate the translation of novel ADCs and ensure the production of effective biosimilars.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. Dipolar NLO Chromophores Bearing Diazine Rings as π-Conjugated Linkers.

    PubMed

    Klikar, Milan; le Poul, Pascal; Růžička, Aleš; Pytela, Oldřich; Barsella, Alberto; Dorkenoo, Kokou D; Robin-le Guen, Françoise; Bureš, Filip; Achelle, Sylvain

    2017-09-15

    The synthesis of a series of push-pull derivatives bearing triphenylamine electron-donating group, cyclopenta[c]thiophen-4,6-dione electron acceptor and various π-linkers including (hetero)aromatic fragments is reported. All target chromophores with systematically varied π-linker structure were further investigated by electrochemistry, absorption measurements, and EFISH experiments in conjunction with DFT calculations. Based on electrochemical and photophysical measurements, when a polarizable 2,5-thienylene moiety is embedded into the chromophore π-backbone the highest intramolecular charge transfer (ICT) is observed. Benzene, pyrimidine, and pyridazine derivatives exhibit lower polarizability and extent of the ICT across these π-linkers. The elongation of the π-conjugated system via additional ethenylene linker results in a significant reduction of the HOMO-LUMO gap and an enhancement of the NLO response. Whereas it does not significantly influence electrochemical and linear optical properties, the orientation of the pyrimidine ring seems to be a key parameter on the μβ value due to significant variation of the dipolar moment (μ) value. In 2a and 2c, pyrimidine is oriented to behave as an acceptor and thus generate dipolar molecule with μ above 5 D, whereas in 2b and 2d ground state dipole moment is significantly reduced. This study seems to indicate a high aromaticity of pyrimidine and pyridazine derivatives, close to the benzene analogues and significantly higher than thiophene analogues.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. Proteolytic Unlocking of Ultrastable Twin-Acylhydrazone Linkers for Lysosomal Acid-Triggered Release of Anticancer Drugs.

    PubMed

    Zheng, Yiwu; Ren, Jing; Wu, Yaqi; Meng, Xiaoting; Zhao, Yibing; Wu, Chuanliu

    2017-09-22

    Targeted prodrugs exploiting cleavable linkers capable of responding to endogenous stimuli have increasingly been explored for cancer therapy. Successful application of these prodrug designs relies on the manipulation of both stability and responsiveness of the cleavable linkers, which, however, are difficult to be finely regulated, particularly for acid-responsive acylhydrazone bonds. Here we developed a new class of peptide-bridged twin-acylhydrazone linkers (PTA linkers) displaying both an ultrahigh stability and a rapid responsiveness-highly stable in neutral and acidic conditions due to the effect of cooperativity between the two acylhydrazone bonds, easily cleavable in acidic conditions after enzymatically triggered unlocking of the two bonds. Moreover, our study shows the design of PTA-linked prodrugs and the proof-of-concept application of the PTA linkers for site-specific release of anticancer drugs into cancer cells.

  16. 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, ...

  17. Human polyhomeotic homolog 3 (PHC3) sterile alpha motif (SAM) linker allows open-ended polymerization of PHC3 SAM.

    PubMed

    Robinson, Angela K; Leal, Belinda Z; Nanyes, David R; Kaur, Yogeet; Ilangovan, Udayar; Schirf, Virgil; Hinck, Andrew P; Demeler, Borries; Kim, Chongwoo A

    2012-07-10

    Sterile alpha motifs (SAMs) are frequently found in eukaryotic genomes. An intriguing property of many SAMs is their ability to self-associate, forming an open-ended polymer structure whose formation has been shown to be essential for the function of the protein. What remains largely unresolved is how polymerization is controlled. Previously, we had determined that the stretch of unstructured residues N-terminal to the SAM of a Drosophila protein called polyhomeotic (Ph), a member of the polycomb group (PcG) of gene silencers, plays a key role in controlling Ph SAM polymerization. Ph SAM with its native linker created shorter polymers compared to Ph SAM attached to either a random linker or no linker. Here, we show that the SAM linker for the human Ph ortholog, polyhomeotic homolog 3 (PHC3), also controls PHC3 SAM polymerization but does so in the opposite fashion. PHC3 SAM with its native linker allows longer polymers to form compared to when attached to a random linker. Attaching the PHC3 SAM linker to Ph SAM also resulted in extending Ph SAM polymerization. Moreover, in the context of full-length Ph protein, replacing the SAM linker with PHC3 SAM linker, intended to create longer polymers, resulted in greater repressive ability for the chimera compared to wild-type Ph. These findings show that polymeric SAM linkers evolved to modulate a wide dynamic range of SAM polymerization abilities and suggest that rationally manipulating the function of SAM containing proteins through controlling their SAM polymerization may be possible.

  18. 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. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. 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.

  20. 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.