Structural Mechanisms of Nucleosome Recognition by Linker Histones.

Science.gov (United States)

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Cellulase linkers are optimized based on domain type and function: insights from sequence analysis, biophysical measurements, and molecular simulation.

Directory of Open Access Journals (Sweden)

Deanne W Sammond

Full Text Available Cellulase enzymes deconstruct cellulose to glucose, and are often comprised of glycosylated linkers connecting glycoside hydrolases (GHs to carbohydrate-binding modules (CBMs. Although linker modifications can alter cellulase activity, the functional role of linkers beyond domain connectivity remains unknown. Here we investigate cellulase linkers connecting GH Family 6 or 7 catalytic domains to Family 1 or 2 CBMs, from both bacterial and eukaryotic cellulases to identify conserved characteristics potentially related to function. Sequence analysis suggests that the linker lengths between structured domains are optimized based on the GH domain and CBM type, such that linker length may be important for activity. Longer linkers are observed in eukaryotic GH Family 6 cellulases compared to GH Family 7 cellulases. Bacterial GH Family 6 cellulases are found with structured domains in either N to C terminal order, and similar linker lengths suggest there is no effect of domain order on length. O-glycosylation is uniformly distributed across linkers, suggesting that glycans are required along entire linker lengths for proteolysis protection and, as suggested by simulation, for extension. Sequence comparisons show that proline content for bacterial linkers is more than double that observed in eukaryotic linkers, but with fewer putative O-glycan sites, suggesting alternative methods for extension. Conversely, near linker termini where linkers connect to structured domains, O-glycosylation sites are observed less frequently, whereas glycines are more prevalent, suggesting the need for flexibility to achieve proper domain orientations. Putative N-glycosylation sites are quite rare in cellulase linkers, while an N-P motif, which strongly disfavors the attachment of N-glycans, is commonly observed. These results suggest that linkers exhibit features that are likely tailored for optimal function, despite possessing low sequence identity. This study suggests

An online substructure identification method for local structural health monitoring

International Nuclear Information System (INIS)

Hou, Jilin; Ou, Jinping; Jankowski, Łukasz

2013-01-01

This paper proposes a substructure isolation method, which uses time series of measured local response for online monitoring of substructures. The proposed monitoring process consists of two key steps: construction of the isolated substructure, and its identification. The isolated substructure is an independent virtual structure, which is numerically isolated from the global structure by placing virtual supports on the interface. First, the isolated substructure is constructed by a specific linear combination of time series of its measured local responses. Then, the isolated substructure is identified using its local natural frequencies extracted from the combined responses. The substructure is assumed to be linear; the outside part of the global structure can have any characteristics. The method has no requirements on the initial state of the structure, and so the process can be carried out repetitively for online monitoring. Online isolation and monitoring is illustrated in a numerical example with a frame model, and then verified in a cantilever beam experiment. (paper)

Hydroquinone–pyrrole dyads with varied linkers

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Hao Huang

2016-01-01

Full Text Available 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.

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

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Fofanov Viacheslav Y

2010-05-01

Full Text Available Abstract 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

Structure and Functions of Linker Histones.

Science.gov (United States)

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.

Jet substructure measurements at ATLAS and CMS

CERN Document Server

Dattagupta, Aparajita; The ATLAS collaboration

2017-01-01

A review is given of recent Run II measurements of jet substructure at CMS and ATLAS, as well of the most relevant measurements from Run I. Quark and gluon discrimination, jet mass and other substructure observable are discussed together with prospects for future measurements with new insight from theory.

Soil and gas and radon entry potentials for substructure surfaces

International Nuclear Information System (INIS)

Harrison, J.; Sextro, R.G.

1990-01-01

This paper reports on measurement techniques and parameters that describe the potential for areas of a building substructure to have high soil gas and radon entry rates which have been developed. Flows and pressures measured at test holes in substructure surfaces while the substructure was intentionally depressurized were used in a highly simplified electrical circuit to model the substructure/soil network. Data from four New Jersey houses indicate that the soil was a factor of two to six times more resistant to soil gas flow than substructure surfaces, concrete slab floors, including perimeter gaps, cracks, and other penetrations, were approximately five times more resistant to soil gas movement than hollow block walls, and radon entry potentials were highest for slab floors. These indices of entry potential may be useful for characterizing the relative leakiness of below-grade substructure surfaces and for determining the selection and placement of radon control systems

Charged Triazole Cross-Linkers for Hyaluronan-Based Hybrid Hydrogels

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Maike Martini

2016-09-01

Full Text Available Polyelectrolyte hydrogels play an important role in tissue engineering and can be produced from natural polymers, such as the glycosaminoglycan hyaluronan. In order to control charge density and mechanical properties of hyaluronan-based hydrogels, we developed cross-linkers with a neutral or positively charged triazole core with different lengths of spacer arms and two terminal maleimide groups. These cross-linkers react with thiolated hyaluronan in a fast, stoichiometric thio-Michael addition. Introducing a positive charge on the core of the cross-linker enabled us to compare hydrogels with the same interconnectivity, but a different charge density. Positively charged cross-linkers form stiffer hydrogels relatively independent of the size of the cross-linker, whereas neutral cross-linkers only form stable hydrogels at small spacer lengths. These novel cross-linkers provide a platform to tune the hydrogel network charge and thus the mechanical properties of the network. In addition, they might offer a wide range of applications especially in bioprinting for precise design of hydrogels.

A Modal-Based Substructure Method Applied to Nonlinear Rotordynamic Systems

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Helmut J. Holl

2009-01-01

Full Text Available The discretisation of rotordynamic systems usually results in a high number of coordinates, so the computation of the solution of the equations of motion is very time consuming. An efficient semianalytic time-integration method combined with a substructure technique is given, which accounts for nonsymmetric matrices and local nonlinearities. The partitioning of the equation of motion into two substructures is performed. Symmetric and linear background systems are defined for each substructure. The excitation of the substructure comes from the given excitation force, the nonlinear restoring force, the induced force due to the gyroscopic and circulatory effects of the substructure under consideration and the coupling force of the substructures. The high effort for the analysis with complex numbers, which is necessary for nonsymmetric systems, is omitted. The solution is computed by means of an integral formulation. A suitable approximation for the unknown coordinates, which are involved in the coupling forces, has to be introduced and the integration results in Green's functions of the considered substructures. Modal analysis is performed for each linear and symmetric background system of the substructure. Modal reduction can be easily incorporated and the solution is calculated iteratively. The numerical behaviour of the algorithm is discussed and compared to other approximate methods of nonlinear structural dynamics for a benchmark problem and a representative example.

Substructuring by Lagrange multipliers for solids and plates

Energy Technology Data Exchange (ETDEWEB)

Mandel, J.; Tezaur, R. [Univ. of Colorado, Denver, CO (United States); Farhat, C. [Univ. of Colorado, Boulder, CO (United States)

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.

Blooming Trees: Substructures and Surrounding Groups of Galaxy Clusters

Science.gov (United States)

Yu, Heng; Diaferio, Antonaldo; Serra, Ana Laura; Baldi, Marco

2018-06-01

We develop the Blooming Tree Algorithm, a new technique that uses spectroscopic redshift data alone to identify the substructures and the surrounding groups of galaxy clusters, along with their member galaxies. Based on the estimated binding energy of galaxy pairs, the algorithm builds a binary tree that hierarchically arranges all of the galaxies in the field of view. The algorithm searches for buds, corresponding to gravitational potential minima on the binary tree branches; for each bud, the algorithm combines the number of galaxies, their velocity dispersion, and their average pairwise distance into a parameter that discriminates between the buds that do not correspond to any substructure or group, and thus eventually die, and the buds that correspond to substructures and groups, and thus bloom into the identified structures. We test our new algorithm with a sample of 300 mock redshift surveys of clusters in different dynamical states; the clusters are extracted from a large cosmological N-body simulation of a ΛCDM model. We limit our analysis to substructures and surrounding groups identified in the simulation with mass larger than 1013 h ‑1 M ⊙. With mock redshift surveys with 200 galaxies within 6 h ‑1 Mpc from the cluster center, the technique recovers 80% of the real substructures and 60% of the surrounding groups; in 57% of the identified structures, at least 60% of the member galaxies of the substructures and groups belong to the same real structure. These results improve by roughly a factor of two the performance of the best substructure identification algorithm currently available, the σ plateau algorithm, and suggest that our Blooming Tree Algorithm can be an invaluable tool for detecting substructures of galaxy clusters and investigating their complex dynamics.

Small but mighty: Dark matter substructures

Science.gov (United States)

Cyr-Racine, Francis-Yan; Keeton, Charles; Moustakas, Leonidas

2018-01-01

The fundamental properties of dark matter, such as its mass, self-interaction, and coupling to other particles, can have a major impact on the evolution of cosmological density fluctuations on small length scales. Strong gravitational lenses have long been recognized as powerful tools to study the dark matter distribution on these small subgalactic scales. In this talk, we discuss how gravitationally lensed quasars and extended lensed arcs could be used to probe non minimal dark matter models. We comment on the possibilities enabled by precise astrometry, deep imaging, and time delays to extract information about mass substructures inside lens galaxies. To this end, we introduce a new lensing statistics that allows for a robust diagnostic of the presence of perturbations caused by substructures. We determine which properties of mass substructures are most readily constrained by lensing data and forecast the constraining power of current and future observations.

Fracture behaviour of zirconia FPDs substructures.

Science.gov (United States)

Kou, W; Sjögren, G

2010-04-01

The purpose of this study was to evaluate the occurrence of superficial flaws after machining and to identify fracture initiation and propagation in three-unit heat-treated machined fixed partial dentures (FPDs) substructures made of hot isostatic pressed (HIPed) yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) after loaded to fracture. Four three-unit HIPed Y-TZP-based FPDs substructures were examined. To evaluate the occurrence of superficial flaws after machining, the surfaces were studied utilizing a fluorescent penetrant method. After static loading to fracture, characteristic fracture features on both mating halves of the fractured specimens were studied using a stereomicroscope and a scanning electron microscope. Grinding grooves were clearly visible on the surfaces of the machined FPDs substructures, but no other flaws could be seen with the fluorescent penetrant method. After loading to fracture, the characteristic fracture features of arrest lines, compression curl, fracture mirror, fracture origin, hackle and twist hackle were detected. These findings indicated that the decisive fracture was initiated at the gingival embrasure of the pontic in association with a grinding groove. Thus, in three-unit heat-treated machined HIPed Y-TZP FPDs substructures, with the shape studied in this study, the gingival embrasure of the pontic seems to be a weak area providing a location for tensile stresses when they are occlusally loaded. In this area, fracture initiation may be located to a grinding groove.

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

Directory of Open Access Journals (Sweden)

Shuji Mizumoto

2015-01-01

Full Text Available 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.

Initial conformation of kinesin's neck linker

International Nuclear Information System (INIS)

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

2014-01-01

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. (interdisciplinary physics and related areas of science and technology)

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

Science.gov (United States)

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.

Nanohashtag structures based on carbon nanotubes and molecular linkers

Science.gov (United States)

Frye, Connor W.; Rybolt, Thomas R.

2018-03-01

Molecular mechanics was used to study the noncovalent interactions between single-walled carbon nanotubes and molecular linkers. Groups of nanotubes have the tendency to form tight, parallel bundles (||||). Molecular linkers were introduced into our models to stabilize nanostructures with carbon nanotubes held in perpendicular orientations. Molecular mechanics makes it possible to estimate the strength of noncovalent interactions holding these structures together and to calculate the overall binding energy of the structures. A set of linkers were designed and built around a 1,3,5,7-cyclooctatetraene tether with two corannulene containing pincers that extend in opposite directions from the central cyclooctatetraene portion. Each pincer consists of a pairs of "arms." These molecular linkers were modified so that the "hand" portions of each pair of "arms" could close together to grab and hold two carbon nanotubes in a perpendicular arrangement. To illustrate the possibility of more complicated and open perpendicular CNTs structures, our primary goal was to create a model of a nanohashtag (#) CNT conformation that is more stable than any parallel CNT arrangements with bound linker molecules forming clumps of CNTs and linkers in non-hashtag arrangements. This goal was achieved using a molecular linker (C280H96) that utilizes van der Waals interactions to two perpendicular oriented CNTs. Hydrogen bonding was then added between linker molecules to augment the stability of the hashtag structure. In the hashtag structure with hydrogen bonding, four (5,5) CNTs of length 4.46 nm (18 rings) and four linkers (C276H92N8O8) stabilized the hashtag so that the average binding energy per pincer was 118 kcal/mol.

A sub-structure method for multidimensional integral transport calculations

International Nuclear Information System (INIS)

Kavenoky, A.; Stankovski, Z.

1983-03-01

A new method has been developed for fine structure burn-up calculations of very heterogeneous large size media. It is a generalization of the well-known surface-source method, allowing coupling actual two-dimensional heterogeneous assemblies, called sub-structures. The method has been applied to a rectangular medium, divided into sub-structures, containing rectangular and/or cylindrical fuel, moderator and structure elements. The sub-structures are divided into homogeneous zones. A zone-wise flux expansion is used to formulate a direct collision probability problem within it (linear or flat flux expansion in the rectangular zones, flat flux in the others). The coupling of the sub-structures is performed by making extra assumptions on the currents entering and leaving the interfaces. The accuracies and computing times achieved are illustrated by numerical results on two benchmark problems

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

Energy Technology Data Exchange (ETDEWEB)

Janesh, William; Morrison, Heather L.; Ma, Zhibo; Harding, Paul [Department of Astronomy, Case Western Reserve University, Cleveland, OH 44106 (United States); Rockosi, Constance [UCO/Lick Observatory, University of California, Santa Cruz, 1156 High Street, Santa Cruz, CA 95064 (United States); Starkenburg, Else [Department of Physics and Astronomy, University of Victoria, P.O. Box 1700, STN CSC, Victoria BC V8W 3P6 (Canada); Xue, Xiang Xiang; Rix, Hans-Walter [Max-Planck-Institut für Astronomie, Königstuhl 17, D-69117 Heidelberg (Germany); Beers, Timothy C. [Department of Physics and JINA Center for the Evolution of the Elements, University of Notre Dame, Notre Dame, IN 46556 (United States); Johnson, Jennifer [Department of Astronomy, Ohio State University, 140 West 18th Avenue, Columbus, OH 43210 (United States); Lee, Young Sun [Department of Astronomy and Space Science, Chungnam National University, Daejeon 34134 (Korea, Republic of); Schneider, Donald P. [Department of Astronomy and Astrophysics, The Pennsylvania State University, University Park, PA 16802 (United States)

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.

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

Science.gov (United States)

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.

Substructural Regularization With Data-Sensitive Granularity for Sequence Transfer Learning.

Science.gov (United States)

Sun, Shichang; Liu, Hongbo; Meng, Jiana; Chen, C L Philip; Yang, Yu

2018-06-01

Sequence transfer learning is of interest in both academia and industry with the emergence of numerous new text domains from Twitter and other social media tools. In this paper, we put forward the data-sensitive granularity for transfer learning, and then, a novel substructural regularization transfer learning model (STLM) is proposed to preserve target domain features at substructural granularity in the light of the condition of labeled data set size. Our model is underpinned by hidden Markov model and regularization theory, where the substructural representation can be integrated as a penalty after measuring the dissimilarity of substructures between target domain and STLM with relative entropy. STLM can achieve the competing goals of preserving the target domain substructure and utilizing the observations from both the target and source domains simultaneously. The estimation of STLM is very efficient since an analytical solution can be derived as a necessary and sufficient condition. The relative usability of substructures to act as regularization parameters and the time complexity of STLM are also analyzed and discussed. Comprehensive experiments of part-of-speech tagging with both Brown and Twitter corpora fully justify that our model can make improvements on all the combinations of source and target domains.

An algebraic sub-structuring method for large-scale eigenvalue calculation

International Nuclear Information System (INIS)

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

2004-01-01

We examine sub-structuring methods for solving large-scale generalized eigenvalue problems from a purely algebraic point of view. We use the term 'algebraic sub-structuring' to refer 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 provide approximate solutions to the original problem. We are interested in the question of which spectral components one should extract from each sub-structure in order to produce an approximate solution to the original problem with a desired level of accuracy. Error estimate for the approximation to the smallest eigenpair is developed. The estimate leads to a simple heuristic for choosing spectral components (modes) from each sub-structure. The effectiveness of such a heuristic is demonstrated with numerical examples. We show that algebraic sub-structuring can be effectively used to solve a generalized eigenvalue problem arising from the simulation of an accelerator structure. One interesting characteristic of this application is that the stiffness matrix produced by a hierarchical vector finite elements scheme contains a null space of large dimension. We present an efficient scheme to deflate this null space in the algebraic sub-structuring process

Composite Octet Searches with Jet Substructure

Energy Technology Data Exchange (ETDEWEB)

Bai, Yang; /SLAC; 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.

Disruption of the IS6-AID linker affects voltage-gated calcium channel inactivation and facilitation.

Science.gov (United States)

Findeisen, Felix; Minor, Daniel L

2009-03-01

Two processes dominate voltage-gated calcium channel (Ca(V)) inactivation: voltage-dependent inactivation (VDI) and calcium-dependent inactivation (CDI). The Ca(V)beta/Ca(V)alpha(1)-I-II loop and Ca(2+)/calmodulin (CaM)/Ca(V)alpha(1)-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-alpha-interaction domain (AID) linker provides a rigid connection between the pore and Ca(V)beta/I-II loop complex by showing that IS6-AID linker polyglycine mutations accelerate Ca(V)1.2 (L-type) and Ca(V)2.1 (P/Q-type) VDI. Remarkably, mutations that either break the rigid IS6-AID linker connection or disrupt Ca(V)beta/I-II association sharply decelerate CDI and reduce a second Ca(2+)/CaM/Ca(V)alpha(1)-C-terminal-mediated process known as calcium-dependent facilitation. Collectively, the data strongly suggest that components traditionally associated solely with VDI, Ca(V)beta and the IS6-AID linker, are essential for calcium-dependent modulation, and that both Ca(V)beta-dependent and CaM-dependent components couple to the pore by a common mechanism requiring Ca(V)beta and an intact IS6-AID linker.

Photolabile linker for the synthesis of hydroxamic acids

DEFF Research Database (Denmark)

2013-01-01

a hydroxylamine - functionalized photolabile linker, and the so produced hydroxylamine - functionalized photolabile solid support. The invention further provides a method for synthesizing a one-bead-one compound library of hydroxamic acid derivatives on a photolabile linker, as well as a method for screening...

Galaxy Clusters: Substructure and Mass Systematics

Science.gov (United States)

Zhang, Yu-Ying

2010-07-01

We calibrate the X-ray measured hydrostatic equilibrium (H.E.) mass and assess the origin of the H.E. mass systematics using 2-D spectrally measured X-ray properties. We obtained that the average X-ray mass derived from H.E. using XMM-Newton data is lower compared to the weak lensing mass from Subaru data for relaxed clusters in a sample of 12 clusters at z~0.2. This is comparable to the expectation of numerical simulations because of the non-thermal pressure support due to turbulence and bulk motions. The gas mass to weak lensing mass ratio shows no dependence on the cluster morphology, which indicates that the gas mass may be a good mass proxy regardless of the cluster dynamical state. To understand the origin of the systematics of the H.E. mass, we investigated 4 nearby clusters, for which the substructure is quantified by the radial fluctuations in the spectrally measured 2-D maps by a cumulative/differential scatter profile relative to the mean profile within/at a given radius. The amplitude of and the discontinuity in the scatter complements 2-D 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 deviation of the H.E. mass relative to the expected mass based on the representative scaling relation, e.g., M-Mgas, particularly at r500-the radius within which the over-density, Δ, is 500 with respect to the critical density. This indicates that at larger radii, the systematic error of the H.E. mass may well be caused by substructure.

Substructure and electrical resistivity analyses of pure tungsten sheet

International Nuclear Information System (INIS)

Trybus, C.L.; Sellers, C.H.; Anderl, R.A.

1991-01-01

The substructure of pure tungsten sheet (0.025 mm thick) is examined and quantified by transmission electron microscopy (TEM). Dislocation populations and arrangements are evaluated for as-worked and various annealed conditions of the tungsten sheet. The worked (rolled) tungsten substructure was nonhomogeneous, consisting of areas of very high and low dislocation densities. These results are correlated to resistivity measurements of the tungsten sheet following thermal cycling to 1200 degrees C to determine the substructural changes as a function of temperature. The comparison between the two characterization techniques is used to examine the relationship between structural and electronic properties in tungsten. 15 refs., 6 figs., 2 tabs

Linker-mediated assembly of gold nanoparticles into multimeric motifs

Energy Technology Data Exchange (ETDEWEB)

Sikora, Mateusz; Cieplak, Marek [Institute of Physics, Polish Academy of Sciences, Aleja Lotnikow 32/46, 02-668 Warsaw (Poland); Szymczak, Piotr [Institute of Theoretical Physics, Faculty of Physics, University of Warsaw, ulica Hoza 69, 00-681 Warsaw (Poland); Thompson, Damien, E-mail: mc@ifpan.edu.pl [Tyndall National Institute, Lee Maltings, University College Cork, Cork (Ireland)

2011-11-04

We present a theoretical description of linker-mediated self-assembly of gold nanoparticles (Au-NP). Using mesoscale simulations with a coarse-grained model for the Au NPs and dirhenium-based linker molecules, we investigate the conditions under which large clusters can grow and construct a phase diagram that identifies favorable growth conditions in terms of floating and bound linker concentrations. The findings can be considered as generic, as we expect other NP-linker systems to behave in a qualitatively similar way. In particular, we also discuss the case of antibody-functionalised Au NPs connected by the C-reactive proteins (CRPs). We extract some general rules for NP linking that may aid the production of size- and shape-specific NP clusters for technology applications.

Analysis and application of European genetic substructure using 300 K SNP information.

Directory of Open Access Journals (Sweden)

Chao Tian

2008-01-01

Full Text Available European population genetic substructure was examined in a diverse set of >1,000 individuals of European descent, each genotyped with >300 K SNPs. Both STRUCTURE and principal component analyses (PCA showed the largest division/principal component (PC differentiated northern from southern European ancestry. A second PC further separated Italian, Spanish, and Greek individuals from those of Ashkenazi Jewish ancestry as well as distinguishing among northern European populations. In separate analyses of northern European participants other substructure relationships were discerned showing a west to east gradient. Application of this substructure information was critical in examining a real dataset in whole genome association (WGA analyses for rheumatoid arthritis in European Americans to reduce false positive signals. In addition, two sets of European substructure ancestry informative markers (ESAIMs were identified that provide substantial substructure information. The results provide further insight into European population genetic substructure and show that this information can be used for improving error rates in association testing of candidate genes and in replication studies of WGA scans.

Construction of hierarchically porous metal-organic frameworks through linker labilization

Science.gov (United States)

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.

Evolution of the degree of substructures in simulated galaxy clusters

Science.gov (United States)

De Boni, Cristiano; Böhringer, Hans; Chon, Gayoung; Dolag, Klaus

2018-05-01

We study the evolution of substructure in the mass distribution with mass, redshift and radius in a sample of simulated galaxy clusters. The sample, containing 1226 objects, spans the mass range M200 = 1014 - 1.74 × 1015 M⊙ h-1 in six redshift bins from z = 0 to z = 1.179. We consider three different diagnostics: 1) subhalos identified with SUBFIND; 2) overdense regions localized by dividing the cluster into octants; 3) offset between the potential minimum and the center of mass. The octant analysis is a new method that we introduce in this work. We find that none of the diagnostics indicate a correlation between the mass of the cluster and the fraction of substructures. On the other hand, all the diagnostics suggest an evolution of substructures with redshift. For SUBFIND halos, the mass fraction is constant with redshift at Rvir, but shows a mild evolution at R200 and R500. Also, the fraction of clusters with at least a subhalo more massive than one thirtieth of the total mass is less than 20%. Our new method based on the octants returns a mass fraction in substructures which has a strong evolution with redshift at all radii. The offsets also evolve strongly with redshift. We also find a strong correlation for individual clusters between the offset and the fraction of substructures identified with the octant analysis. Our work puts strong constraints on the amount of substructures we expect to find in galaxy clusters and on their evolution with redshift.

Dynamic analysis of clustered building structures using substructures methods

International Nuclear Information System (INIS)

Leimbach, K.R.; Krutzik, N.J.

1989-01-01

The dynamic substructure approach to the building cluster on a common base mat starts with the generation of Ritz-vectors for each building on a rigid foundation. The base mat plus the foundation soil is subjected to kinematic constraint modes, for example constant, linear, quadratic or cubic constraints. These constraint modes are also imposed on the buildings. By enforcing kinematic compatibility of the complete structural system on the basis of the constraint modes a reduced Ritz model of the complete cluster is obtained. This reduced model can now be analyzed by modal time history or response spectrum methods

Identifying a new particle with jet substructures

CERN Document Server

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

2017-01-01

We investigate a potential of measuring properties of a heavy resonance X, exploiting jet substructure techniques. Motivated by heavy higgs boson searches, we focus on the decays of X into a pair of (massive) electroweak gauge bosons. More specifically, we consider a hadronic Z boson, which makes it possible to determine properties of X at an earlier stage. For $m_X$ of O(1) TeV, two quarks from a Z boson would be captured as a "merged jet" in a significant fraction of events. The use of the merged jet enables us to consider a Z-induced jet as a reconstructed object without any combinatorial ambiguity. We apply a conventional jet substructure method to extract four-momenta of subjets from a merged jet. We find that jet substructure procedures may enhance features in some kinematic observables formed with subjets. Subjet momenta are fed into the matrix element associated with a given hypothesis on the nature of X, which is further processed to construct a matrix element method (MEM)-based observable. For both ...

Social-group identity and population substructure in admixed populations in New Mexico and Latin America.

Directory of Open Access Journals (Sweden)

Meghan E Healy

Full Text Available We examined the relationship between continental-level genetic ancestry and racial and ethnic identity in an admixed population in New Mexico with the goal of increasing our understanding of how racial and ethnic identity influence genetic substructure in admixed populations. Our sample consists of 98 New Mexicans who self-identified as Hispanic or Latino (NM-HL and who further categorized themselves by race and ethnic subgroup membership. The genetic data consist of 270 newly-published autosomal microsatellites from the NM-HL sample and previously published data from 57 globally distributed populations, including 13 admixed samples from Central and South America. For these data, we 1 summarized the major axes of genetic variation using principal component analyses, 2 performed tests of Hardy Weinberg equilibrium, 3 compared empirical genetic ancestry distributions to those predicted under a model of admixture that lacked substructure, 4 tested the hypotheses that individuals in each sample had 100%, 0%, and the sample-mean percentage of African, European, and Native American ancestry. We found that most NM-HL identify themselves and their parents as belonging to one of two groups, conforming to a region-specific narrative that distinguishes recent immigrants from Mexico from individuals whose families have resided in New Mexico for generations and who emphasize their Spanish heritage. The "Spanish" group had significantly lower Native American ancestry and higher European ancestry than the "Mexican" group. Positive FIS values, PCA plots, and heterogeneous ancestry distributions suggest that most Central and South America admixed samples also contain substructure, and that this substructure may be related to variation in social identity. Genetic substructure appears to be common in admixed populations in the Americas and may confound attempts to identify disease-causing genes and to understand the social causes of variation in health outcomes

Substructure identification for shear structures: cross-power spectral density method

International Nuclear Information System (INIS)

Zhang, Dongyu; Johnson, Erik A

2012-01-01

In this paper, a substructure identification method for shear structures is proposed. A shear structure is divided into many small substructures; utilizing the dynamic equilibrium of a one-floor substructure, an inductive identification problem is formulated, using the cross-power spectral densities between structural floor accelerations and a reference response, to estimate the parameters of that one story. Repeating this procedure, all story parameters of the shear structure are identified from top to bottom recursively. An identification error analysis is performed for the proposed substructure method, revealing how uncertain factors (e.g. measurement noise) in the identification process affect the identification accuracy. According to the error analysis, a smart reference selection rule is designed to choose the optimal reference response that further enhances the identification accuracy. Moreover, based on the identification error analysis, explicit formulae are developed to calculate the variances of the parameter identification errors. A ten-story shear structure is used to illustrate the effectiveness of the proposed substructure method. The simulation results show that the method, combined with the reference selection rule, can very accurately identify structural parameters despite large measurement noise. Furthermore, the proposed formulae provide good predictions for the variances of the parameter identification errors, which are vital for providing accurate warnings of structural damage. (paper)

Improved sensitivity of a graphene FET biosensor using porphyrin linkers

Science.gov (United States)

Kawata, Takuya; Ono, Takao; Kanai, Yasushi; Ohno, Yasuhide; Maehashi, Kenzo; Inoue, Koichi; Matsumoto, Kazuhiko

2018-06-01

Graphene FET (G-FET) biosensors have considerable potential due to the superior characteristics of graphene. Realizing this potential requires judicious choice of the linker molecule connecting the target-specific receptor molecule to the graphene surface, yet there are few reports comparing linker molecules for G-FET biosensors. In this study, tetrakis(4-carboxyphenyl)porphyrin (TCPP) was used as a linker for surface modification of a G-FET and the properties of the device were compared to those of a G-FET device modified with the conventional linker 1-pyrenebutanoic acid succinimidyl ester (PBASE). TCPP modification resulted in a higher density of receptor immunoglobulin E (IgE) aptamer molecules on the G-FET. The detection limit of the target IgE was enhanced from 13 nM for the PBASE-modified G-FET to 2.2 nM for the TCPP-modified G-FET, suggesting that the TCPP linker is a powerful candidate for G-FET modification.

A Traceless Aryl-Triazene Linker for DNA-Directed Chemistry

DEFF Research Database (Denmark)

Hejesen, Christian; Pedersen, Lars Kolster; Gothelf, Kurt Vesterager

2013-01-01

DNA-directed synthesis of encoded combinatorial libraries of small organic compounds most often involves transfer of organic building blocks from one DNA strand to another. This requires cleavable linkers to enable cleavage of the link to the original DNA strand from which the building block...... is transferred. Relatively few cleavable linkers are available for DNA-directed synthesis and most often they leave an amino group at the organic molecule. Here we have extended the application of 10 aryltriazenes as traceless linkers for DNA-directed synthesis. After reaction of one building block...

Substructure method of soil-structure interaction analysis for earthquake loadings

Energy Technology Data Exchange (ETDEWEB)

Park, H. G.; Joe, Y. H. [Industrial Development Research Center, Univ. of Incheon, Incheon (Korea, Republic of)

1997-07-15

Substructure method has been preferably adopted for soil-structure interaction analysis because of its simplicity and economy in practical application. However, substructure method has some limitation in application and does not always give reliable results especially for embedded structures or layered soil conditions. The objective of this study to validate the reliability of the soil-structure interaction analysis results by the proposed substructure method using lumped-parameter model and suggest a method of seismic design of nuclear power plant structures with specific design conditions. In this study, theoretic background and modeling technique of soil-structure interaction phenomenon have been reviewed and an analysis technique based on substructure method using lumped-parameter model has been suggested. The practicality and reliability of the proposed method have been validated through the application of the method to the seismic analysis of the large-scale seismic test models. A technical guide for practical application and evaluation of the proposed method have been also provided through the various type parametric.

Gas expulsion in highly substructured embedded star clusters

Science.gov (United States)

Farias, J. P.; Fellhauer, M.; Smith, R.; Domínguez, R.; Dabringhausen, J.

2018-06-01

We investigate the response of initially substructured, young, embedded star clusters to instantaneous gas expulsion of their natal gas. We introduce primordial substructure to the stars and the gas by simplistically modelling the star formation process so as to obtain a variety of substructure distributed within our modelled star-forming regions. We show that, by measuring the virial ratio of the stars alone (disregarding the gas completely), we can estimate how much mass a star cluster will retain after gas expulsion to within 10 per cent accuracy, no matter how complex the background structure of the gas is, and we present a simple analytical recipe describing this behaviour. We show that the evolution of the star cluster while still embedded in the natal gas, and the behaviour of the gas before being expelled, is crucial process that affect the time-scale on which the cluster can evolve into a virialized spherical system. Embedded star clusters that have high levels of substructure are subvirial for longer times, enabling them to survive gas expulsion better than a virialized and spherical system. By using a more realistic treatment for the background gas than our previous studies, we find it very difficult to destroy the young clusters with instantaneous gas expulsion. We conclude that gas removal may not be the main culprit for the dissolution of young star clusters.

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

International Nuclear Information System (INIS)

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

2016-01-01

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. (paper)

Towards an understanding of jet substructure

CERN Document Server

Dasgupta, Mrinal; Marzani, Simone; Salam, Gavin P

2013-01-01

We present first analytic, resummed calculations of the rates at which widespread jet substructure tools tag QCD jets. As well as considering trimming, pruning and the mass-drop tagger, we introduce modified tools with improved analytical and phenomenological behaviours. Most taggers have double logarithmic resummed structures. The modified mass-drop tagger is special in that it involves only single logarithms, and is free from a complex class of terms known as non-global logarithms. The modification of pruning brings an improved ability to discriminate between the different colour structures that characterise signal and background. As we outline in an extensive phenomenological discussion, these results provide valuable insight into the performance of existing tools and help lay robust foundations for future substructure studies.

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

International Nuclear Information System (INIS)

Wing, Joshua D.; Blanton, Elizabeth L.

2013-01-01

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.

Searches for new physics using jet grooming and substructure

CERN Document Server

Burr, Jonathan Thomas Peter; The ATLAS collaboration

2017-01-01

Models predicting the production and decay of supersymmetric (SUSY) particles often have promising search channels involving decays through heavy intermediate states such as top quarks and heavy bosons. However, unlike in most exotics scenarios these heavy states are only moderately boosted which can make traditional substructure techniques less useful and motivates the development of alternative techniques. The results of several SUSY analyses using substructure techniques are presented.

A NEW METHOD TO QUANTIFY X-RAY SUBSTRUCTURES IN CLUSTERS OF GALAXIES

Energy Technology Data Exchange (ETDEWEB)

Andrade-Santos, Felipe; Lima Neto, Gastao B.; Lagana, Tatiana F. [Departamento de Astronomia, Instituto de Astronomia, Geofisica e Ciencias Atmosfericas, Universidade de Sao Paulo, Geofisica e Ciencias Atmosfericas, Rua do Matao 1226, Cidade Universitaria, 05508-090 Sao Paulo, SP (Brazil)

2012-02-20

We present a new method to quantify substructures in clusters of galaxies, based on the analysis of the intensity of structures. This analysis is done in a residual image that is the result of the subtraction of a surface brightness model, obtained by fitting a two-dimensional analytical model ({beta}-model or Sersic profile) with elliptical symmetry, from the X-ray image. Our method is applied to 34 clusters observed by the Chandra Space Telescope that are in the redshift range z in [0.02, 0.2] and have a signal-to-noise ratio (S/N) greater than 100. We present the calibration of the method and the relations between the substructure level with physical quantities, such as the mass, X-ray luminosity, temperature, and cluster redshift. We use our method to separate the clusters in two sub-samples of high- and low-substructure levels. We conclude, using Monte Carlo simulations, that the method recuperates very well the true amount of substructure for small angular core radii clusters (with respect to the whole image size) and good S/N observations. We find no evidence of correlation between the substructure level and physical properties of the clusters such as gas temperature, X-ray luminosity, and redshift; however, analysis suggest a trend between the substructure level and cluster mass. The scaling relations for the two sub-samples (high- and low-substructure level clusters) are different (they present an offset, i.e., given a fixed mass or temperature, low-substructure clusters tend to be more X-ray luminous), which is an important result for cosmological tests using the mass-luminosity relation to obtain the cluster mass function, since they rely on the assumption that clusters do not present different scaling relations according to their dynamical state.

Creating Hierarchical Pores by Controlled Linker Thermolysis in Multivariate Metal-Organic Frameworks.

Science.gov (United States)

Feng, Liang; Yuan, Shuai; Zhang, Liang-Liang; Tan, Kui; Li, Jia-Luo; Kirchon, Angelo; Liu, Ling-Mei; Zhang, Peng; Han, Yu; Chabal, Yves J; Zhou, Hong-Cai

2018-02-14

Sufficient pore size, appropriate stability, and hierarchical porosity are three prerequisites for open frameworks designed for drug delivery, enzyme immobilization, and catalysis involving large molecules. Herein, we report a powerful and general strategy, linker thermolysis, to construct ultrastable hierarchically porous metal-organic frameworks (HP-MOFs) with tunable pore size distribution. Linker instability, usually an undesirable trait of MOFs, was exploited to create mesopores by generating crystal defects throughout a microporous MOF crystal via thermolysis. The crystallinity and stability of HP-MOFs remain after thermolabile linkers are selectively removed from multivariate metal-organic frameworks (MTV-MOFs) through a decarboxylation process. A domain-based linker spatial distribution was found to be critical for creating hierarchical pores inside MTV-MOFs. Furthermore, linker thermolysis promotes the formation of ultrasmall metal oxide nanoparticles immobilized in an open framework that exhibits high catalytic activity for Lewis acid-catalyzed reactions. Most importantly, this work provides fresh insights into the connection between linker apportionment and vacancy distribution, which may shed light on probing the disordered linker apportionment in multivariate systems, a long-standing challenge in the study of MTV-MOFs.

Backbone amide linker strategy

DEFF Research Database (Denmark)

Shelton, Anne Pernille Tofteng; Jensen, Knud Jørgen

2013-01-01

In the backbone amide linker (BAL) strategy, the peptide is anchored not at the C-terminus but through a backbone amide, which leaves the C-terminal available for various modifications. This is thus a very general strategy for the introduction of C-terminal modifications. The BAL strategy...

Rational design of molecularly imprinted polymer: the choice of cross-linker.

Science.gov (United States)

Muhammad, Turghun; Nur, Zohre; Piletska, Elena V; Yimit, Osmanjan; Piletsky, Sergey A

2012-06-07

The paper describes a rational approach for the selection of cross-linkers during the development of molecularly imprinted polymers (MIPs). As a model system for this research MIPs specific for the drug zidovudine (AZT) were designed and tested. Three cross-linkers trimethylolpropane trimethacrylate (TRIM), ethylene glycol dimethacrylate (EGDMA) and divinylbenzene (DVB) were studied. The analogue of zidovudine (AZT) ester (AZT-ES) was used as a dummy template. The imprinting factors for all of the polymers in the static adsorption experiments were calculated. The data on the AZT adsorption by control polymers (CP), which were prepared with different cross-linkers without a functional monomer, was also analyzed. DVB was found to be more inert towards zidovudine than EGDMA and TRIM, which was confirmed by both molecular modelling and adsorption experiments. It was demonstrated that DVB-based polymers had a higher imprinting factor (I = 1.85) compared with other tested cross-linked polymers. It was suggested that the selection of the cross-linker should be based on the strength of the interaction with the template: the cross-linker which displays lower binding of the template should be preferential because it generates MIPs with lower non-specific binding and a higher imprinting factor, and therefore specificity. Which cross-linker to use for the preparation of any particular MIP can be determined by analysis of the interactions between the cross-linker and template. This could be done either virtually using computational modelling or by template adsorption using a small library of polymers prepared using different cross-linkers.

Vector boson tagged jets and jet substructure

Directory of Open Access Journals (Sweden)

Vitev Ivan

2018-01-01

Full Text Available In these proceedings, we report on recent results related to vector boson-tagged jet production in heavy ion collisions and the related modification of jet substructure, such as jet shapes and jet momentum sharing distributions. Z0-tagging and γ-tagging of jets provides new opportunities to study parton shower formation and propagation in the quark-gluon plasma and has been argued to provide tight constrains on the energy loss of reconstructed jets. We present theoretical predictions for isolated photon-tagged and electroweak boson-tagged jet production in Pb+Pb collisions at √sNN = 5.02 TeV at the LHC, addressing the modification of their transverse momentum and transverse momentum imbalance distributions. Comparison to recent ATLAS and CMS experimental measurements is performed that can shed light on the medium-induced radiative corrections and energy dissipation due to collisional processes of predominantly quark-initiated jets. The modification of parton splitting functions in the QGP further implies that the substructure of jets in heavy ion collisions may differ significantly from the corresponding substructure in proton-proton collisions. Two such observables and the implication of tagging on their evaluation is also discussed.

Star formation and substructure in galaxy clusters

International Nuclear Information System (INIS)

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

2014-01-01

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 r 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.

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

Science.gov (United States)

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

Creating Hierarchical Pores by Controlled Linker Thermolysis in Multivariate Metal-Organic Frameworks

KAUST Repository

Feng, Liang

2018-01-18

Sufficient pore size, appropriate stability and hierarchical porosity are three prerequisites for open frameworks designed for drug delivery, enzyme immobilization and catalysis involving large molecules. Herein, we report a powerful and general strate-gy, linker thermolysis, to construct ultra-stable hierarchically porous metal−organic frameworks (HP-MOFs) with tunable pore size distribution. Linker instability, usually an undesirable trait of MOFs, was exploited to create mesopores by generating crystal defects throughout a microporous MOF crystal via thermolysis. The crystallinity and stability of HP-MOFs remain after thermolabile linkers are selectively removed from multivariate metal-organic frameworks (MTV-MOFs) through a decarboxyla-tion process. A domain-based linker spatial distribution was found to be critical for creating hierarchical pores inside MTV-MOFs. Furthermore, linker thermolysis promotes the formation of ultra-small metal oxide (MO) nanoparticles immobilized in an open framework that exhibits high catalytic activity for Lewis acid catalyzed reactions. Most importantly, this work pro-vides fresh insights into the connection between linker apportionment and vacancy distribution, which may shed light on prob-ing the disordered linker apportionment in multivariate systems, a long-standing challenge in the study of MTV-MOFs.

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

Science.gov (United States)

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.

Improving substructure identification accuracy of shear structures using virtual control system

Science.gov (United States)

Zhang, Dongyu; Yang, Yang; Wang, Tingqiang; Li, Hui

2018-02-01

Substructure identification is a powerful tool to identify the parameters of a complex structure. Previously, the authors developed an inductive substructure identification method for shear structures. The identification error analysis showed that the identification accuracy of this method is significantly influenced by the magnitudes of two key structural responses near a certain frequency; if these responses are unfavorable, the method cannot provide accurate estimation results. In this paper, a novel method is proposed to improve the substructure identification accuracy by introducing a virtual control system (VCS) into the structure. A virtual control system is a self-balanced system, which consists of some control devices and a set of self-balanced forces. The self-balanced forces counterbalance the forces that the control devices apply on the structure. The control devices are combined with the structure to form a controlled structure used to replace the original structure in the substructure identification; and the self-balance forces are treated as known external excitations to the controlled structure. By optimally tuning the VCS’s parameters, the dynamic characteristics of the controlled structure can be changed such that the original structural responses become more favorable for the substructure identification and, thus, the identification accuracy is improved. A numerical example of 6-story shear structure is utilized to verify the effectiveness of the VCS based controlled substructure identification method. Finally, shake table tests are conducted on a 3-story structural model to verify the efficacy of the VCS to enhance the identification accuracy of the structural parameters.

Substructuring in the implicit simulation of single point incremental sheet forming

NARCIS (Netherlands)

Hadoush, A.; van den Boogaard, Antonius H.

2009-01-01

This paper presents a direct substructuring method to reduce the computing time of implicit simulations of single point incremental forming (SPIF). Substructuring is used to divide the finite element (FE) mesh into several non-overlapping parts. Based on the hypothesis that plastic deformation is

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

Science.gov (United States)

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.

Mass-stiffness substructuring of an elastic metasurface for full transmission beam steering

Science.gov (United States)

Lee, Hyuk; Lee, Jun Kyu; Seung, Hong Min; Kim, Yoon Young

2018-03-01

The metasurface concept has a significant potential due to its novel wavefront-shaping functionalities that can be critically useful for ultrasonic and solid wave-based applications. To achieve the desired functionalities, elastic metasurfaces should cover full 2π phase shift and also acquire full transmission within subwavelength scale. However, they have not been explored much with respect to the elastic regime, because the intrinsic proportionality of mass-stiffness within the continuum elastic media causes an inevitable trade-off between abrupt phase shift and sufficient transmission. Our goal is to engineer an elastic metasurface that can realize an inverse relation between (amplified) effective mass and (weakened) stiffness in order to satisfy full 2π phase shift as well as full transmission. To achieve this goal, we propose a continuum elastic metasurface unit cell that is decomposed into two substructures, namely a mass-tuning substructure with a local dipolar resonator and a stiffness-tuning substructure composed of non-resonant multiply-perforated slits. We demonstrate analytically, numerically, and experimentally that this unique substructured unit cell can satisfy the required phase shift with high transmission. The substructuring enables independent tuning of the elastic properties over a wide range of values. We use a mass-spring model of the proposed continuum unit cell to investigate the working mechanism of the proposed metasurface. With the designed metasurface consisting of substructured unit cells embedded in an aluminum plate, we demonstrate that our metasurface can successfully realize anomalous steering and focusing of in-plane longitudinal ultrasonic beams. The proposed substructuring concept is expected to provide a new principle for the design of general elastic metasurfaces that can be used to efficiently engineer arbitrary wave profiles.

Dislocation-Disclination Substructures Formed in FCC Polycrystals Under Large Plastic Deformations: Evolution and Association with Flow Stress

Science.gov (United States)

Kozlov, É. V.; Koneva, N. A.; Trishkina, L. I.

2014-06-01

The evolution of dislocation substructures formed in polycrystalline Cu-Al and Cu-Mn alloys undergoing large plastic deformations is studied, using transmission electron microscopy. Microband and fragmented substructures are examined. The Al and Mn alloying element concentrations for which the substructures are formed have been found. The mechanisms involved in the formation of the substructures during the substructural evolution in the alloys subjected to deformation have been revealed. Parameters describing the substructures under study have been measured. The dependence of the parameters on the flow stress has been established.

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

Science.gov (United States)

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...

A streptavidin linker layer that functions after drying.

Science.gov (United States)

Xia, Nan; Shumaker-Parry, Jennifer S; Zareie, M Hadi; Campbell, Charles T; Castner, David G

2004-04-27

The ability of streptavidin (SA) to simultaneously bind four biotins is often used in linker layers, where a biotinylated molecule is linked to a biotin-functionalized surface via SA. For biosensor and array applications, it is desirable that the SA linker layer be stable to drying and rehydration. In this study it was observed that a significant decrease in binding capacity of a SA layer occurred when that layer was dried. For this study a SA linker layer was constructed by binding SA to a biotin-containing alkylthiolate monolayer (BAT/OEG) self-assembled onto gold. Its stability after drying was investigated using surface plasmon resonance (SPR). Approximately a quarter of the SA layer was removed from the BAT/OEG surface upon drying and rehydration, suggesting disruption of SA-biotin binding when dry. This resulted in the dried SA layer losing approximately 40% of its biotinylated ferritin (BF) binding capacity. Coating the layer with trehalose before drying was found to inhibit the loss of SA from the BAT/OEG surface. SPR showed that the trehalose-protected SA linker layer retained approximately 91% of its original BF binding capacity after drying and rehydration. Atomic force microscopy, which was used to image individual surface-bound SA and BF molecules, qualitatively confirmed these observations.

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

Energy Technology Data Exchange (ETDEWEB)

Roettgen, Dan [Wisc; Seeger, Benjamin [Stuttgart; Tai, Wei Che [Washington; Baek, Seunghun [Michigan; Dossogne, Tilan [Liege; Allen, Matthew S [Wisc; 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.

Identifying a new particle with jet substructures

International Nuclear Information System (INIS)

Han, Chengcheng; Kim, Doojin; Kim, Minho; Postech, Pohang

2017-01-01

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 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. Finally, we discuss effects from choosing different jet sizes for merged jets and jet-grooming parameters upon the MEM analyses.

Investigation of the Linker Swing Motion in the Zeolitic Imidazolate Framework ZIF-90

KAUST Repository

Zheng, Bin

2018-03-13

The linker swing motion in the zeolitic imidazolate framework ZIF-90 is investigated by density functional theory (DFT) calculation, molecular dynamics (MD) and grand-canonical Monte Carlo (GCMC) simulations. The relation between the terminal aldehyde group rotation and the linker swing motion is revealed. The extremely high activation energy of the linker swing motion in ZIF-90 can be attributed to the asymmetric geometry and electron distribution of aldehyde groups. The change in the gate structure resulting from the linker rotation is used to understand the guest adsorption in ZIF-90. This study shows that it is possible to tune the linker swing motion and then the properties of ZIF-90 by manipulating the terminal group rotation. The results highlight the importance of considering the internal freedom effects to correctly describe the linker swing motion and the flexibility of metal-organic frameworks (MOFs).

QUANTIFYING KINEMATIC SUBSTRUCTURE IN THE MILKY WAY'S STELLAR HALO

International Nuclear Information System (INIS)

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; Weaver, Benjamin A.

2011-01-01

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 gc < 20 kpc.

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

DEFF Research Database (Denmark)

Dandolo, Corinna Ludovica Koch; Fukunaga, Kaori; Kohzuma, Yoshei

2017-01-01

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...... 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...

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

DEFF Research Database (Denmark)

Bahrt, Frederikke; Daugaard, Anders Egede; Hvilsted, Søren

2013-01-01

-(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......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...

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

Science.gov (United States)

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

Antibodies directed to drug epitopes to investigate the structure of drug-protein photoadducts. Recognition of a common photobound substructure in tiaprofenic acid/ketoprofen cross-photoreactivity.

Science.gov (United States)

Lahoz, A; Hernández, D; Miranda, M A; Pérez-Prieto, J; Morera, I M; Castell, J V

2001-11-01

Drug-induced photoallergy is an immune adverse reaction to the combined effect of drugs and light. From the mechanistic point of view, it first involves covalent binding of drug to protein resulting in the formation of a photoantigen. Hence, determination of the structures of drug-protein photoadducts is of great relevance to understand the molecular basis of photoallergy and cross-immunoreactivity among drugs. Looking for new strategies to investigate the covalent photobinding of drugs to proteins, we generated highly specific antibodies to drug chemical substructures. The availability of such antibodies has allowed us to discriminate between the different modes by which tiaprofenic acid (TPA), suprofen (SUP), and ketoprofen (KTP) photobind to proteins. The finding that the vast majority of the TPA photoadduct can be accounted for by means of antibody anti-benzoyl strongly supports the view that the drug binds preferentially via the thiophene ring, leaving the benzene ring more accessible. By contrast, selective recognition of SUP-protein photoadducts by antibody anti-thenoyl evidences a preferential coupling via the benzene ring leaving the thiophene moiety more distant from the protein matrix. In the case of KTP, photoadducts are exclusively recognized by antibody anti-benzoyl, indicating that the benzene ring is again more accessible. As a result of this research, we have been able to identify a common substructure that is present in TPA-albumin and KTP-albumin photoadducts. This is remarkable since, at a first sight, the greatest structural similarities can be found between TPA and SUP as they share the same benzoylthiophene chromophore. These findings can explain the previously reported observations of cross-reactivity to KTP (or TPA) in patients photosensitized to TPA (or KTP).

Tagging partially reconstructed objects with jet substructure

Energy Technology Data Exchange (ETDEWEB)

Freytsis, Marat, E-mail: freytsis@uoregon.edu [Department of Physics, Harvard University, Cambridge, MA, 02138 (United States); Volansky, Tomer [Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University, Tel-Aviv 69978 (Israel); Walsh, Jonathan R. [Ernest Orlando Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720 (United States); Berkeley Center for Theoretical Physics, University of California, Berkeley, CA 94720 (United States)

2017-06-10

We present a new tagger which aims at identifying partially reconstructed objects, in which only some of the constituents are collected in a single jet. As an example, we focus on top decays in which either part of the hadronically decaying W or the b jet is soft or falls outside of the top jet cone. We construct an observable to identify remnant substructure from the decay and employ aggressive jet grooming to reject QCD backgrounds. The tagger is complementary to existing ones and works well in the intermediate boost regime where jet substructure techniques usually fail. It is anticipated that a similar tagger can be used to identify non-QCD hadronic jets, such as those expected from hidden valleys.

Tagging partially reconstructed objects with jet substructure

International Nuclear Information System (INIS)

Freytsis, Marat; Volansky, Tomer; Walsh, Jonathan R.

2017-01-01

We present a new tagger which aims at identifying partially reconstructed objects, in which only some of the constituents are collected in a single jet. As an example, we focus on top decays in which either part of the hadronically decaying W or the b jet is soft or falls outside of the top jet cone. We construct an observable to identify remnant substructure from the decay and employ aggressive jet grooming to reject QCD backgrounds. The tagger is complementary to existing ones and works well in the intermediate boost regime where jet substructure techniques usually fail. It is anticipated that a similar tagger can be used to identify non-QCD hadronic jets, such as those expected from hidden valleys.

Tagging partially reconstructed objects with jet substructure

Science.gov (United States)

Freytsis, Marat; Volansky, Tomer; Walsh, Jonathan R.

2017-06-01

We present a new tagger which aims at identifying partially reconstructed objects, in which only some of the constituents are collected in a single jet. As an example, we focus on top decays in which either part of the hadronically decaying W or the b jet is soft or falls outside of the top jet cone. We construct an observable to identify remnant substructure from the decay and employ aggressive jet grooming to reject QCD backgrounds. The tagger is complementary to existing ones and works well in the intermediate boost regime where jet substructure techniques usually fail. It is anticipated that a similar tagger can be used to identify non-QCD hadronic jets, such as those expected from hidden valleys.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Monte Carlo analysis of neck linker extension in kinesin molecular motors.

Directory of Open Access Journals (Sweden)

Matthew L Kutys

2010-11-01

Full Text Available Kinesin stepping is thought to involve both concerted conformational changes and diffusive movement, but the relative roles played by these two processes are not clear. The neck linker docking model is widely accepted in the field, but the remainder of the step--diffusion of the tethered head to the next binding site--is often assumed to occur rapidly with little mechanical resistance. Here, we investigate the effect of tethering by the neck linker on the diffusive movement of the kinesin head, and focus on the predicted behavior of motors with naturally or artificially extended neck linker domains. The kinesin chemomechanical cycle was modeled using a discrete-state Markov chain to describe chemical transitions. Brownian dynamics were used to model the tethered diffusion of the free head, incorporating resistive forces from the neck linker and a position-dependent microtubule binding rate. The Brownian dynamics and chemomechanical cycle were coupled to model processive runs consisting of many 8 nm steps. Three mechanical models of the neck linker were investigated: Constant Stiffness (a simple spring, Increasing Stiffness (analogous to a Worm-Like Chain, and Reflecting (negligible stiffness up to a limiting contour length. Motor velocities and run lengths from simulated paths were compared to experimental results from Kinesin-1 and a mutant containing an extended neck linker domain. When tethered by an increasingly stiff spring, the head is predicted to spend an unrealistically short amount of time within the binding zone, and extending the neck is predicted to increase both the velocity and processivity, contrary to experiments. These results suggest that the Worm-Like Chain is not an adequate model for the flexible neck linker domain. The model can be reconciled with experimental data if the neck linker is either much more compliant or much stiffer than generally assumed, or if weak kinesin-microtubule interactions stabilize the diffusing

Misoriented dislocation substructures and the fracture of polycrystalline Cu-Al alloys

Science.gov (United States)

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

2016-10-01

The evolution of the dislocation substructure in polycrystalline Cu-Al alloys with various grain sizes is studied during deformation to failure. A relation between the fracture of the alloys and the forming misorientation dislocation substructures is revealed. Microcracks in the alloy are found to form along grain boundaries and the boundaries of misoriented dislocation cells and microtwins.

MAPPING THE GALACTIC HALO. VIII. QUANTIFYING SUBSTRUCTURE

International Nuclear Information System (INIS)

Starkenburg, Else; Helmi, Amina; Van Woerden, Hugo; Morrison, Heather L.; Harding, Paul; Frey, Lucy; Oravetz, Dan; Mateo, Mario; Dohm-Palmer, R. C.; Olszewski, Edward W.; Sivarani, Thirupathi; Norris, John E.; Freeman, Kenneth C.; Shectman, Stephen A.

2009-01-01

We have measured the amount of kinematic substructure in the Galactic halo using the final data set from the Spaghetti project, a pencil-beam high-latitude sky survey. Our sample contains 101 photometrically selected and spectroscopically confirmed giants with accurate distance, radial velocity, and metallicity information. We have developed a new clustering estimator: the '4distance' measure, which when applied to our data set leads to the identification of one group and seven pairs of clumped stars. The group, with six members, can confidently be matched to tidal debris of the Sagittarius dwarf galaxy. Two pairs match the properties of known Virgo structures. Using models of the disruption of Sagittarius in Galactic potentials with different degrees of dark halo flattening, we show that this favors a spherical or prolate halo shape, as demonstrated by Newberg et al. using the Sloan Digital Sky Survey data. One additional pair can be linked to older Sagittarius debris. We find that 20% of the stars in the Spaghetti data set are in substructures. From comparison with random data sets, we derive a very conservative lower limit of 10% to the amount of substructure in the halo. However, comparison to numerical simulations shows that our results are also consistent with a halo entirely built up from disrupted satellites, provided that the dominating features are relatively broad due to early merging or relatively heavy progenitor satellites.

Natural draft cooling tower with shell disconnected from the substructure

International Nuclear Information System (INIS)

Diver, Marius

1982-01-01

The aim of this paper is the analysis of results of a research done by Electricite de France, concerning a new type of cooling tower. The traditional structure (i.e. a hyperbolic shell supported by X shaped or diagonal columns) is replaced by two independent structures: the shell, becoming a self-contained structure, the lower rim being stiffened by an annular beam; the substructure, resting on the soil. This new type of cooling tower has an improved thermal performance due to the increase of the area of air entrance. Bearing pads are provided between the lower ring beam of the shell and the substructure. Any differential settlement can be coped with by jacking. The water distribution structure can be laid out so as to benefit from advantages offered by the presence of the stiff ring and columns of the substructure [fr

Stick-slip substructure in rapid tape peeling

KAUST Repository

Thoroddsen, Sigurdur T.

2010-10-15

The peeling of adhesive tape is known to proceed with a stick-slip mechanism and produces a characteristic ripping sound. The peeling also produces light and when peeled in a vacuum, even X-rays have been observed, whose emissions are correlated with the slip events. Here we present direct imaging of the detachment zone when Scotch tape is peeled off at high speed from a solid surface, revealing a highly regular substructure, during the slip phase. The typical 4-mm-long slip region has a regular substructure of transverse 220 μm wide slip bands, which fracture sideways at speeds over 300 m/s. The fracture tip emits waves into the detached section of the tape at ∼100 m/s, which promotes the sound, so characteristic of this phenomenon.

Stick-slip substructure in rapid tape peeling

KAUST Repository

Thoroddsen, Sigurdur T; Nguyen, H. D.; Takehara, K.; Etoh, T. G.

2010-01-01

The peeling of adhesive tape is known to proceed with a stick-slip mechanism and produces a characteristic ripping sound. The peeling also produces light and when peeled in a vacuum, even X-rays have been observed, whose emissions are correlated with the slip events. Here we present direct imaging of the detachment zone when Scotch tape is peeled off at high speed from a solid surface, revealing a highly regular substructure, during the slip phase. The typical 4-mm-long slip region has a regular substructure of transverse 220 μm wide slip bands, which fracture sideways at speeds over 300 m/s. The fracture tip emits waves into the detached section of the tape at ∼100 m/s, which promotes the sound, so characteristic of this phenomenon.

LRRC45 Is a Centrosome Linker Component Required for Centrosome Cohesion

Directory of Open Access Journals (Sweden)

Runsheng He

2013-09-01

Full Text Available During interphase, centrosomes are connected by a proteinaceous linker between the proximal ends of the centrioles, which is important for the centrosomes to function as a single microtubule-organizing center. However, the composition and regulation of centrosomal linker remain largely unknown. Here, we show that LRRC45 is a centrosome linker that localizes at the proximal ends of the centrioles and forms fiber-like structures between them. Depletion of LRRC45 results in centrosome splitting during interphase. Moreover, LRRC45 interacts with both C-Nap1 and rootletin and is phosphorylated by Nek2A at S661 during mitosis. After phosphorylation, both LRRC45 centrosomal localization and fiber-like structures are significantly reduced, which subsequently leads to centrosome separation. Thus, LRRC45 is a critical component of the proteinaceous linker between two centrioles and is required for centrosome cohesion.

Water-soluble heterobifunctional fluorescent linkers

Czech Academy of Sciences Publication Activity Database

Bartoň, Jan; Cígler, Petr

2017-01-01

Roč. 15, č. 1 (2017), s. 4 ISSN 2336-7202. [Mezioborové setkání mladých biologů, biochemiků a chemiků /17./. 30.05.2017-01.06.2017, Milovy] Institutional support: RVO:61388963 Keywords : fluorescent probes * heterobifunctional linkers Subject RIV: CA - Inorganic Chemistry

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

Science.gov (United States)

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

THE UNORTHODOX ORBITS OF SUBSTRUCTURE HALOS

NARCIS (Netherlands)

Ludlow, Aaron D.; Navarro, Julio F.; Springel, Volker; Jenkins, Adrian; Frenk, Carlos S.; Helmi, Amina

2009-01-01

We use a suite of cosmological N-body simulations to study the properties of substructure halos (subhalos) in galaxy-sized cold dark matter halos. We extend prior work on the subject by considering the whole population of subhalos physically associated with the main system. These are defined as

Systematic benchmark of substructure search in molecular graphs - From Ullmann to VF2

Directory of Open Access Journals (Sweden)

Ehrlich Hans-Christian

2012-07-01

Full Text Available Abstract Background Searching for substructures in molecules belongs to the most elementary tasks in cheminformatics and is nowadays part of virtually every cheminformatics software. The underlying algorithms, used over several decades, are designed for the application to general graphs. Applied on molecular graphs, little effort has been spend on characterizing their performance. Therefore, it is not clear how current substructure search algorithms behave on such special graphs. One of the main reasons why such an evaluation was not performed in the past was the absence of appropriate data sets. Results In this paper, we present a systematic evaluation of Ullmann’s and the VF2 subgraph isomorphism algorithms on molecular data. The benchmark set consists of a collection of 1235 SMARTS substructure expressions and selected molecules from the ZINC database. The benchmark evaluates substructures search times for complete database scans as well as individual substructure-molecule pairs. In detail, we focus on the influence of substructure formulation and size, the impact of molecule size, and the ability of both algorithms to be used on multiple cores. Conclusions The results show a clear superiority of the VF2 algorithm in all test scenarios. In general, both algorithms solve most instances in less than one millisecond, which we consider to be acceptable. Still, in direct comparison, the VF2 is most often several folds faster than Ullmann’s algorithm. Additionally, Ullmann’s algorithm shows a surprising number of run time outliers.

Structural analysis and optimization procedure of the TFTR device substructure

International Nuclear Information System (INIS)

Driesen, G.

1975-10-01

A structural evaluation of the TFTR device substructure is performed in order to verify the feasibility of the proposed design concept as well as to establish a design optimization procedure for minimizing the material and fabrication cost of the substructure members. A preliminary evaluation of the seismic capability is also presented. The design concept on which the analysis is based is consistent with that described in the Conceptual Design Status Briefing report dated June 18, 1975

Some sub-structures of many-particle correlation in nuclei

Energy Technology Data Exchange (ETDEWEB)

Chang, C; Chao, W; Li, K

1977-01-01

The coherent structures of two phonons were proposed as the sub-structure ..cap alpha..' of four-particle clusters for the light nuclei. In the same way the sub-structure ..beta../sup +/ of four-hole clusters can also be given. Based on this the sub-structures between particle clusters and hole clusters in /sup 16/O and /sup 18/O were chosen as examples for investigation. It is found that there is a very strong repulsive force between them. Therefore the loose structure between particle cluster and hole cluster is of the lowest energy state. In this way, the deformations of these states were explained from the microscopic structures. Moreover, these structures can coherently strengthen the E2 transition. Further in order to study the particle correlation in the medium nuclei, the L-S coupling coherent structure is extended to the pseudo L-S coupling coherent structure and the expressions are given in the j-j coupling representation. Some preliminary analyses are made for the nuclei around /sup 56/Ni by using these structures.

Evolutionarily conserved substrate substructures for automated annotation of enzyme superfamilies.

Directory of Open Access Journals (Sweden)

Ranyee A Chiang

2008-08-01

Full Text Available 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

Evolutionarily conserved substrate substructures for automated annotation of enzyme superfamilies.

Science.gov (United States)

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

Full Vehicle Vibration and Noise Analysis Based on Substructure Power Flow

Directory of Open Access Journals (Sweden)

Zhien Liu

2017-01-01

Full Text Available Combining substructure and power flow theory, in this paper an external program is written to control MSC. Nastran solution process and the substructure frequency response are also formulated accordingly. Based on a simple vehicle model, characteristics of vibration, noise, and power flow are studied, respectively. After being compared with the result of conventional FEM (finite element method, the new method is confirmed to be feasible. When it comes to a vehicle with the problem of low-frequency noise, finite element models of substructures for vehicle body and chassis are established, respectively. In addition, substructure power flow method is also employed to examine the transfer characteristics of multidimensional vibration energy for the whole vehicle system. By virtue of the adjustment stiffness of drive shaft support and bushes at rear suspension lower arm, the vehicle interior noise is decreased by about 3 dB when the engine speed is near 1050 rpm and 1650 rpm in experiment. At the same time, this method can increase the computation efficiency by 78%, 38%, and 98% when it comes to the optimization of chassis structure, body structure, and vibration isolation components, respectively.

Jet Substructure at the Tevatron and LHC: New results, new tools, new benchmarks

CERN Document Server

Altheimer, A; Asquith, L; Brooijmans, G; Butterworth, J; Campanelli, M; Chapleau, B; Cholakian, A E; Chou, J P; Dasgupta, M; Davison, A; Dolen, J; Ellis, S D; Essig, R; Fan, J J; Field, R; Fregoso, A; Gallicchio, J; Gershtein, Y; Gomes, A; Haas, A; Halkiadakis, E; Halyo, V; Hoeche, S; Hook, A; Hornig, A; Huang, P; Izaguirre, E; Jankowiak, M; Kribs, G; Krohn, D; Larkoski, A J; Lath, A; Lee, C; Lee, S J; Loch, P; Maksimovic, P; Martinez, M; Miller, D W; Plehn, T; Prokofiev, K; Rahmat, R; Rappoccio, S; Safonov, A; Salam, G P; Schumann, S; Schwartz, M D; Schwartzman, A; Seymour, M; Shao, J; Sinervo, P; Son, M; Soper, D E; Spannowsky, M; Stewart, I W; Strassler, M; Strauss, E; Takeuchi, M; Thaler, J; Thomas, S; Tweedie, B; Vasquez Sierra, R; Vermilion, C K; Villaplana, M; Vos, M; Wacker, J; Walker, D; Walsh, J R; Wang, L-T; Wilbur, S; Yavin, I; Zhu, W

2012-01-01

In this report we review recent theoretical progress and the latest experimental results in jet substructure from the Tevatron and the LHC. We review the status of and outlook for calculation and simulation tools for studying jet substructure. Following up on the report of the Boost 2010 workshop, we present a new set of benchmark comparisons of substructure techniques, focusing on the set of variables and grooming methods that are collectively known as "top taggers". To facilitate further exploration, we have attempted to collect, harmonise, and publish software implementations of these techniques.

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

International Nuclear Information System (INIS)

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

2013-01-01

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 ∼10 8 M ☉ with high significance in most lensed DSFGs. Specifically, we find that in typical DSFG lenses, there is a ∼55% probability of detecting a substructure with M > 10 8 M ☉ with more than 5σ 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 ∼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.

The importance of calorimetry for highly-boosted jet substructure

Energy Technology Data Exchange (ETDEWEB)

Coleman, Evan [Brown U.; Freytsis, Marat [Oregon U.; Hinzmann, Andreas [Hamburg U.; Narain, Meenakshi [Brown U.; Thaler, Jesse [MIT, Cambridge, CTP; Tran, Nhan [Fermilab; Vernieri, Caterina [Fermilab

2017-09-25

Jet substructure techniques are playing an essential role in exploring the TeV scale at the Large Hadron Collider (LHC), since they facilitate the efficient reconstruction and identification of highly-boosted objects. Both for the LHC and for future colliders, there is a growing interest in using jet substructure methods based only on charged-particle information. The reason is that silicon-based tracking detectors offer excellent granularity and precise vertexing, which can improve the angular resolution on highly-collimated jets and mitigate the impact of pileup. In this paper, we assess how much jet substructure performance degrades by using track-only information, and we demonstrate physics contexts in which calorimetry is most beneficial. Specifically, we consider five different hadronic final states - W bosons, Z bosons, top quarks, light quarks, gluons - and test the pairwise discrimination power with a multi-variate combination of substructure observables. In the idealized case of perfect reconstruction, we quantify the loss in discrimination performance when using just charged particles compared to using all detected particles. We also consider the intermediate case of using charged particles plus photons, which provides valuable information about neutral pions. In the more realistic case of a segmented calorimeter, we assess the potential performance gains from improving calorimeter granularity and resolution, comparing a CMS-like detector to more ambitious future detector concepts. Broadly speaking, we find large performance gains from neutral-particle information and from improved calorimetry in cases where jet mass resolution drives the discrimination power, whereas the gains are more modest if an absolute mass scale calibration is not required.

CHEMTRAN and the Interconversion of Chemical Substructure Systems

Science.gov (United States)

Granito, Charles E.

1973-01-01

The need for the interconversion of chemical substructure systems is discussed and CHEMTRAN, a new service, designed especially for creating interconversion programs, is introduced. (7 references) (Author)

A note on the substructural hierarchy

Czech Academy of Sciences Publication Activity Database

Jeřábek, Emil

2016-01-01

Roč. 62, 1-2 (2016), s. 102-110 ISSN 0942-5616 EU Projects: European Commission(XE) 339691 - FEALORA Institutional support: RVO:67985840 Keywords : substructural hierarchy * full Lambek calculus * extension variables Subject RIV: BA - General Mathematics Impact factor: 0.250, year: 2016 http://dx.doi.org/10.1002/malq.201500066

Development of new methodologies to assess the structural integrity of the grouted joint of a 10MW wind turbine substructure

DEFF Research Database (Denmark)

Santos, Benjamin; Gintautas, Tomas; Sørensen, John Dalsgaard

2018-01-01

Monopiles are currently the most commonly used substructure in the offshore wind market due to their ease of installation in shallow to medium waters. The monopile and the transition piece are connected by a grouted joint. Fatigue and corrosion are two of the most important degradation mechanisms...

Substructure based modeling of nickel single crystals cycled at low plastic strain amplitudes

Science.gov (United States)

Zhou, Dong

In this dissertation a meso-scale, substructure-based, composite single crystal model is fully developed from the simple uniaxial model to the 3-D finite element method (FEM) model with explicit substructures and further with substructure evolution parameters, to simulate the completely reversed, strain controlled, low plastic strain amplitude cyclic deformation of nickel single crystals. Rate-dependent viscoplasticity and Armstrong-Frederick type kinematic hardening rules are applied to substructures on slip systems in the model to describe the kinematic hardening behavior of crystals. Three explicit substructure components are assumed in the composite single crystal model, namely "loop patches" and "channels" which are aligned in parallel in a "vein matrix," and persistent slip bands (PSBs) connected in series with the vein matrix. A magnetic domain rotation model is presented to describe the reverse magnetostriction of single crystal nickel. Kinematic hardening parameters are obtained by fitting responses to experimental data in the uniaxial model, and the validity of uniaxial assumption is verified in the 3-D FEM model with explicit substructures. With information gathered from experiments, all control parameters in the model including hardening parameters, volume fraction of loop patches and PSBs, and variation of Young's modulus etc. are correlated to cumulative plastic strain and/or plastic strain amplitude; and the whole cyclic deformation history of single crystal nickel at low plastic strain amplitudes is simulated in the uniaxial model. Then these parameters are implanted in the 3-D FEM model to simulate the formation of PSB bands. A resolved shear stress criterion is set to trigger the formation of PSBs, and stress perturbation in the specimen is obtained by several elements assigned with PSB material properties a priori. Displacement increment, plastic strain amplitude control and overall stress-strain monitor and output are carried out in the user

Stability and function of interdomain linker variants of glucoamylase 1 from Aspergillus niger.

Science.gov (United States)

Sauer, J; Christensen, T; Frandsen, T P; Mirgorodskaya, E; McGuire, K A; Driguez, H; Roepstorff, P; Sigurskjold, B W; Svensson, B

2001-08-07

Several variants of glucoamylase 1 (GA1) from Aspergillus niger were created in which the highly O-glycosylated peptide (aa 468--508) connecting the (alpha/alpha)(6)-barrel catalytic domain and the starch binding domain was substituted at the gene level by equivalent segments of glucoamylases from Hormoconis resinae, Humicola grisea, and Rhizopus oryzae encoding 5, 19, and 36 amino acid residues. Variants were constructed in which the H. resinae linker was elongated by proline-rich sequences as this linker itself apparently was too short to allow formation of the corresponding protein variant. Size and isoelectric point of GA1 variants reflected differences in linker length, posttranslational modification, and net charge. While calculated polypeptide chain molecular masses for wild-type GA1, a nonnatural proline-rich linker variant, H. grisea, and R. oryzae linker variants were 65,784, 63,777, 63,912, and 65,614 Da, respectively, MALDI-TOF-MS gave values of 82,042, 73,800, 73,413, and 90,793 Da, respectively, where the latter value could partly be explained by an N-glycosylation site introduced near the linker C-terminus. The k(cat) and K(m) for hydrolysis of maltooligodextrins and soluble starch, and the rate of hydrolysis of barley starch granules were essentially the same for the variants as for wild-type GA1. beta-Cyclodextrin, acarbose, and two heterobidentate inhibitors were found by isothermal titration calorimetry to bind to the catalytic and starch binding domains of the linker variants, indicating that the function of the active site and the starch binding site was maintained. The stability of GA1 linker variants toward GdnHCl and heat, however, was reduced compared to wild-type.

Creating Hierarchical Pores by Controlled Linker Thermolysis in Multivariate Metal-Organic Frameworks

KAUST Repository

Feng, Liang; Yuan, Shuai; Zhang, Liang-Liang; Tan, Kui; Li, Jia-Luo; Kirchon, Angelo; Liu, Ling-Mei; Zhang, Peng; Han, Yu; Chabal, Yves J.; Zhou, Hong-Cai

2018-01-01

strate-gy, linker thermolysis, to construct ultra-stable hierarchically porous metal−organic frameworks (HP-MOFs) with tunable pore size distribution. Linker instability, usually an undesirable trait of MOFs, was exploited to create mesopores

Improving jet substructure performance in ATLAS using Track-CaloClusters

CERN Document Server

The ATLAS collaboration

2017-01-01

Jet substructure techniques play a critical role in ATLAS in searches for new physics, are increasingly important in measurements of the Standard Model, and are being utilized in the trigger. To date, ATLAS has mostly focused on the use of calorimeter-based jet substructure, which works well for jets initiated by particles with low to moderate boost, but which lacks the angular resolution needed to resolve the desired substructure in the highly-boosted regime. We present a novel approach designed to mitigate the calorimeter angular resolution limitations, thus providing superior performance to prior methods. Similarly to the previously developed combined mass technique, the superior angular resolution of the tracker is combined with information from the calorimeters. However, the new method is fundamentally different, as it correlates low-level objects such as tracks and individual energy deposits in the calorimeter, before running any jet finding algorithms. The resulting objects are used as inputs to jet re...

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

Leandro Martínez

Full Text Available 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.

Tunable CO 2 Adsorbents by Mixed-Linker Synthesis and Postsynthetic Modification of Zeolitic Imidazolate Frameworks

KAUST Repository

Thompson, Joshua A.; Brunelli, Nicholas A.; Lively, Ryan P.; Johnson, J. R.; Jones, Christopher W.; Nair, Sankar

2013-01-01

The incorporation of accessible amine functionality in zeolitic imidazolate frameworks (ZIFs) is used to improve the adsorption selectivity for CO 2/CH4 gas separation applications. Two synthetic approaches are described in this work to introduce functionality into the ZIF: (i) mixed-linker ZIF synthesis with 2-aminobenzimidazole as a substitution linker and (ii) postsynthetic modification of a mixed-linker ZIF with ethylenediamine. Using 2-aminobenzimidazole, a linker with a primary amine functional group, substitution of the ZIF-8 linker during synthesis allows for control over the adsorption properties while maintaining the ZIF-8 structure with up to nearly 50% substitution in the mixed-linker ZIF framework, producing a material with tunable pore size and amine functionality. Alternatively, postsynthetic modification of a mixed-linker ZIF containing an aldehyde functional group produces a ZIF material with a primary amine without detrimental loss of micropore volume by controlling the amount of functional group sites for modification. Both approaches using mixed-linker ZIFs yield new materials that show improvement in adsorption selectivity for the CO 2/CH4 gas pair over ZIF-8 and commercially available adsorbents as well as an increase in the heat of adsorption for CO2 without significant changes to the crystal structure. These results indicate that tuning the surface properties of ZIFs by either mixed-linker synthesis and/or postsynthetic modification may generate new materials with improved gas separation properties, thereby providing a new method for tailoring metal-organic frameworks. © 2013 American Chemical Society.

Tunable CO 2 Adsorbents by Mixed-Linker Synthesis and Postsynthetic Modification of Zeolitic Imidazolate Frameworks

KAUST Repository

Thompson, Joshua A.

2013-04-25

The incorporation of accessible amine functionality in zeolitic imidazolate frameworks (ZIFs) is used to improve the adsorption selectivity for CO 2/CH4 gas separation applications. Two synthetic approaches are described in this work to introduce functionality into the ZIF: (i) mixed-linker ZIF synthesis with 2-aminobenzimidazole as a substitution linker and (ii) postsynthetic modification of a mixed-linker ZIF with ethylenediamine. Using 2-aminobenzimidazole, a linker with a primary amine functional group, substitution of the ZIF-8 linker during synthesis allows for control over the adsorption properties while maintaining the ZIF-8 structure with up to nearly 50% substitution in the mixed-linker ZIF framework, producing a material with tunable pore size and amine functionality. Alternatively, postsynthetic modification of a mixed-linker ZIF containing an aldehyde functional group produces a ZIF material with a primary amine without detrimental loss of micropore volume by controlling the amount of functional group sites for modification. Both approaches using mixed-linker ZIFs yield new materials that show improvement in adsorption selectivity for the CO 2/CH4 gas pair over ZIF-8 and commercially available adsorbents as well as an increase in the heat of adsorption for CO2 without significant changes to the crystal structure. These results indicate that tuning the surface properties of ZIFs by either mixed-linker synthesis and/or postsynthetic modification may generate new materials with improved gas separation properties, thereby providing a new method for tailoring metal-organic frameworks. © 2013 American Chemical Society.

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

Energy Technology Data Exchange (ETDEWEB)

Hezaveh, Yashar; Holder, Gilbert [Department of Physics, McGill University, 3600 Rue University, Montreal, Quebec H3A 2T8 (Canada); Dalal, Neal [Astronomy Department, University of Illinois at Urbana-Champaign, 1002 West Green Street, Urbana, IL 61801 (United States); Kuhlen, Michael [Theoretical Astrophysics Center, University of California, Berkeley, CA 94720 (United States); Marrone, Daniel [Steward Observatory, University of Arizona, 933 North Cherry Avenue, Tucson, AZ 85721 (United States); Murray, Norman [CITA, University of Toronto, 60 St. George Street, Toronto, ON M5S 3H8 (Canada); Vieira, Joaquin [California Institute of Technology, 1200 East California Blvd, MC 249-17, Pasadena, CA 91125 (United States)

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.

Smart variations: Functional substructures for part compatibility

KAUST Repository

Zheng, Youyi

2013-05-01

As collections of 3D models continue to grow, reusing model parts allows generation of novel model variations. Naïvely swapping parts across models, however, leads to implausible results, especially when mixing parts across different model families. Hence, the user has to manually ensure that the final model remains functionally valid. We claim that certain symmetric functional arrangements (sFarr-s), which are special arrangements among symmetrically related substructures, bear close relation to object functions. Hence, we propose a purely geometric approach based on such substructures to match, replace, and position triplets of parts to create non-trivial, yet functionally plausible, model variations. We demonstrate that starting even from a small set of models such a simple geometric approach can produce a diverse set of non-trivial and plausible model variations. © 2013 The Author(s) Computer Graphics Forum © 2013 The Eurographics Association and Blackwell Publishing Ltd.

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

OpenAIRE

Over, Ryan S.; Michaels, Scott D.

2014-01-01

Linker histones play key roles alongside core histones in the regulation and maintenance of chromatin. Here, we illustrate our current understanding of the contributions of linker histones to the cell cycle, development, and chromatin structure in plants and animals.

Novel silicone compatible cross-linkers for controlled functionalization of PDMS networks

DEFF Research Database (Denmark)

Madsen, Frederikke Bahrt; Daugaard, Anders Egede; Hvilsted, Søren

2013-01-01

. In order to improve the dielectric properties of PDMS a novel system is developed where push-pull dipoles are grafted to a new silicone compatible cross-linker. The grafted cross-linkers are prepared by reaction of two different push-pull dipole alkynes as well as a fluorescent alkyne with the new azide...

A finite element based substructuring procedure for design analysis of large smart structural systems

International Nuclear Information System (INIS)

Ashwin, U; Raja, S; Dwarakanathan, D

2009-01-01

A substructuring based design analysis procedure is presented for large smart structural system using the Craig–Bampton method. The smart structural system is distinctively characterized as an active substructure, modelled as a design problem, and a passive substructure, idealized as an analysis problem. Furthermore, a novel thought has been applied by introducing the electro–elastic coupling into the reduction scheme to solve the global structural control problem in a local domain. As an illustration, a smart composite box beam with surface bonded actuators/sensors is considered, and results of the local to global control analysis are presented to show the potential use of the developed procedure. The present numerical scheme is useful for optimally designing the active substructures to study their locations, coupled structure–actuator interaction and provide a solution to the global design of large smart structural systems

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

Science.gov (United States)

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

DASS: efficient discovery and p-value calculation of substructures in unordered data.

Science.gov (United States)

Hollunder, Jens; Friedel, Maik; Beyer, Andreas; Workman, Christopher T; Wilhelm, Thomas

2007-01-01

Pattern identification in biological sequence data is one of the main objectives of bioinformatics research. However, few methods are available for detecting patterns (substructures) in unordered datasets. Data mining algorithms mainly developed outside the realm of bioinformatics have been adapted for that purpose, but typically do not determine the statistical significance of the identified patterns. Moreover, these algorithms do not exploit the often modular structure of biological data. We present the algorithm DASS (Discovery of All Significant Substructures) that first identifies all substructures in unordered data (DASS(Sub)) in a manner that is especially efficient for modular data. In addition, DASS calculates the statistical significance of the identified substructures, for sets with at most one element of each type (DASS(P(set))), or for sets with multiple occurrence of elements (DASS(P(mset))). The power and versatility of DASS is demonstrated by four examples: combinations of protein domains in multi-domain proteins, combinations of proteins in protein complexes (protein subcomplexes), combinations of transcription factor target sites in promoter regions and evolutionarily conserved protein interaction subnetworks. The program code and additional data are available at http://www.fli-leibniz.de/tsb/DASS

Revealing dark matter substructure with anisotropies in the diffuse gamma-ray background

International Nuclear Information System (INIS)

Siegal-Gaskins, Jennifer M

2008-01-01

The majority of gamma-ray emission from galactic dark matter annihilation is likely to be detected as a contribution to the diffuse gamma-ray background. I show that dark matter substructure in the halo of the Galaxy induces characteristic anisotropies in the diffuse background that could be used to determine the small-scale dark matter distribution. I calculate the angular power spectrum of the emission from dark matter substructure for several models of the subhalo population and show that features in the power spectrum can be used to infer the presence of substructure. The shape of the power spectrum is largely unaffected by the subhalo radial distribution and mass function, and for many scenarios I find that a measurement of the angular power spectrum by Fermi will be able to constrain the abundance of substructure. An anti-biased subhalo radial distribution is shown to produce emission that differs significantly in intensity and large-scale angular dependence from that of a subhalo distribution which traces the smooth dark matter halo, potentially impacting the detectability of the dark matter signal for a variety of targets and methods

Revealing dark matter substructure with anisotropies in the diffuse gamma-ray background

Energy Technology Data Exchange (ETDEWEB)

Siegal-Gaskins, Jennifer M, E-mail: jsg@kicp.uchicago.edu [Kavli Institute for Cosmological Physics and Department of Physics, University of Chicago, 5640 S. Ellis Avenue, Chicago, IL 60637 (United States)

2008-10-15

The majority of gamma-ray emission from galactic dark matter annihilation is likely to be detected as a contribution to the diffuse gamma-ray background. I show that dark matter substructure in the halo of the Galaxy induces characteristic anisotropies in the diffuse background that could be used to determine the small-scale dark matter distribution. I calculate the angular power spectrum of the emission from dark matter substructure for several models of the subhalo population and show that features in the power spectrum can be used to infer the presence of substructure. The shape of the power spectrum is largely unaffected by the subhalo radial distribution and mass function, and for many scenarios I find that a measurement of the angular power spectrum by Fermi will be able to constrain the abundance of substructure. An anti-biased subhalo radial distribution is shown to produce emission that differs significantly in intensity and large-scale angular dependence from that of a subhalo distribution which traces the smooth dark matter halo, potentially impacting the detectability of the dark matter signal for a variety of targets and methods.

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

Energy Technology Data Exchange (ETDEWEB)

Johnson, Michael D. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Gwinn, Carl R., E-mail: mjohnson@cfa.harvard.edu [Department of Physics, University of California, Santa Barbara, CA 93106 (United States)

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.

Spatial Substructure in the M87 Globular Cluster System

Science.gov (United States)

Feng, Yuting; Zhang, Yunhao; Guhathakurta, Puragra; Peng, Eric; Lim, Sungsoon

2018-01-01

Based on the observation of Next Generation Virgo Cluster Survey (NGVS) project, we obtained the u,g,r,i,z and Ks band photometric information of all the objects in the 2 degree × 2 degree area (Pilot Region) around M87, the major subcluster of Virgo. By adapting an Extreme Deconvolution method, which classifies objects into Globular Clusters (GCs), galaxies and foreground stars with their color and morphology data, we got a purer-than-ever GC distribution map with a depth to gmag=25 in Pilot Region. After masking galaxy GCs, smoothing with a 10arcmin Gaussian kernel and performing a flat field correction, we show the GC density map of M87, and got a good sersic fitting of GC radial distribution with a sersic index~2.2 in the central ellipse part (45arcmin semi major axis area of M87). We quantitatively compared our GC sample with a substructure-free mock data set, which was generated from the smoothed density map as well as the sersic fitting, by calculating the 2 point correlation function (TPCF) value in different parts of the map. After separately performing such comparison with mocks based on different galaxy masking radii which vary from 4 times g band effective radius to 10, we found signals of remarkable spatial enhancement in certain directions in the central ellipse of M87, as well as halo substructures shown as lumpiness and holes in the outer region. We present the estimated scales of these substructures from the TPCF results, and, managed to locate them with a statistical analysis of the pixelized GC map. Apart from all results listed above, we discuss the constant, extra-galactic substructure signal at a scale of ~3kpc, which does not diminish with masking sizes, as the evidence of merging and accretion history of M87.

Deformation behavior of a 16-8-2 GTA weld as influenced by its solidification substructure

International Nuclear Information System (INIS)

Foulds, J.R.; Moteff, J.; Sikka, V.K.; McEnerney, J.W.

1983-01-01

Weldment sections from formed and welded type 316 stainless steel pipe are characterized with respect to some time-independent (tensile) and time-dependent (creep) mechanical properties at temperatures between 25 0 C and 649 0 C. The GTA weldment, welded with 16-8-2 filler metal, is sectioned from pipe in the formed + welded + solution annealed + straightened condition, as well as in the same condition with an additional re-solution treatment. Detailed room temperature microhardness measurements on these sections before and after reannealing enable a determination of the different recovery characteristics of weld and base metal. The observed stable weld metal solidification dislocation substructure in comparison with the base metal random dislocation structure, in fact, adequately explains weld/base metal elevated temperature mechanical behavior differences from this recovery characteristic standpoint. The weld metal substructure is the only parameter common to the variety of austenitic stainless steel welds exhibiting the consistent parent/weld metal deformation behavior differences described. As such, it must be considered the key to understanding weldment mechanical behavior

Observations of Cluster Substructure using Weakly Lensed Sextupole Moments

Energy Technology Data Exchange (ETDEWEB)

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.

The measles virus phosphoprotein interacts with the linker domain of STAT1

International Nuclear Information System (INIS)

Devaux, Patricia; Priniski, Lauren; Cattaneo, Roberto

2013-01-01

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

The measles virus phosphoprotein interacts with the linker domain of STAT1

Energy Technology Data Exchange (ETDEWEB)

Devaux, Patricia, E-mail: devaux.patricia@mayo.edu; 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.

Rapid bridge construction technology : precast elements for substructures.

Science.gov (United States)

2011-06-01

The goal of this research was to propose an alternate system of precast bridge substructures which can : substitute for conventional cast in place systems in Wisconsin to achieve accelerated construction. : Three types of abutment modules (hollow wal...

Improving jet substructure in ATLAS using unified track and calorimeter information

CERN Document Server

Schramm, Steven; The ATLAS collaboration

2017-01-01

Jet substructure techniques play a critical role in ATLAS in searches for new physics, are increasingly important in measurements of the Standard Model, and are being utilized in the trigger. To date, ATLAS has mostly focused on the use of calorimeter-based jet substructure, which works well for jets initiated by particles with low to moderate boost, but which lacks the angular resolution needed to resolve the desired substructure in the highly-boosted regime. We will present a novel approach designed to mitigate the calorimeter angular resolution limitations, thus providing superior performance to prior methods. Similar to previous methods, the superior angular resolution of the tracker is combined with information from the calorimeters. However, the new method is fundamentally different, as it correlates low-level objects as tracks and individual energy deposits in the calorimeter, before running any jet finding algorithms. The resulting objects are used as inputs to jet reconstruction, and in turn result i...

On substructuring algorithms and solution techniques for the numerical approximation of partial differential equations

Science.gov (United States)

Gunzburger, M. D.; Nicolaides, R. A.

1986-01-01

Substructuring methods are in common use in mechanics problems where typically the associated linear systems of algebraic equations are positive definite. Here these methods are extended to problems which lead to nonpositive definite, nonsymmetric matrices. The extension is based on an algorithm which carries out the block Gauss elimination procedure without the need for interchanges even when a pivot matrix is singular. Examples are provided wherein the method is used in connection with finite element solutions of the stationary Stokes equations and the Helmholtz equation, and dual methods for second-order elliptic equations.

Development of Bioorthogonally Degradable Linkers and Polymers Using alpha-Azidoethers

Science.gov (United States)

Rajagopalan, Chandrasekhar Ramasubramanian

Degradable polymers have gained a lot of attention in recent years for applications in biotechnology and medicine. External control over polymer degradation can be obtained by incorporating functional groups that cleave in the presence of triggers that would normally be absent in biological environments, i.e. are bioorthogonal. This thesis explores the use of chemically cleavable alpha-azidoethers as a new method to obtain external control over the degradation behavior of polymers. My first goal is to illustrate the potential of alpha-azidoethers toward developing cleavable linkers. We have studied the relationship between alpha-azidoether structure and hydrolytic stability, to prepare linkers that withstand background hydrolytic cleavage until they are exposed to the cleaving trigger. The cleavage kinetics of the alpha-azidoether functional group was quantified. In addition to the conventionally used tris(2-carboxyethyl)phosphine (TCEP), dihydrolipoic acid (DHLA), a previously unexplored, biocompatible reducing agent, was also evaluated as a cleaving trigger. Based on these results, we have proposed design rules for utilizing alpha-azidoethers as cleavable linkers in applications that require bioorthogonal control over linker cleavage. Secondly, the alpha-azidoether cleavable linker chemistry was implemented into the development of polymeric materials. Two different types of polymers were developed. Polyamides incorporating alpha-azidoethers along the backbone were synthesized, and their physical properties and chemically triggered degradation behavior were characterized. The degradation timescale of these polymers can be tuned simply by manipulating the concentration of the externally applied chemical trigger. The alpha-azidoether functional group was then utilized to develop a unique triggered-release polymeric adhesive for potential applications in dental adhesive formulations. A methacrylamide-phosphonate adhesive monomer incorporating an alpha

Modeling of rail track substructure linear elastic coupling

Science.gov (United States)

2015-09-30

Most analyses of rail dynamics neglect contribution of the soil, or treat it in a very simple manner such as using spring elements. This can cause accuracy issues in examining dynamics for passenger comfort, derailment, substructure analysis, or othe...

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

Science.gov (United States)

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.

Elastin-like Polypeptide Linkers for Single-Molecule Force Spectroscopy.

Science.gov (United States)

Ott, Wolfgang; Jobst, Markus A; Bauer, Magnus S; Durner, Ellis; Milles, Lukas F; Nash, Michael A; Gaub, Hermann E

2017-06-27

Single-molecule force spectroscopy (SMFS) is by now well established as a standard technique in biophysics and mechanobiology. In recent years, the technique has benefitted greatly from new approaches to bioconjugation of proteins to surfaces. Indeed, optimized immobilization strategies for biomolecules and refined purification schemes are being steadily adapted and improved, which in turn has enhanced data quality. In many previously reported SMFS studies, poly(ethylene glycol) (PEG) was used to anchor molecules of interest to surfaces and/or cantilever tips. The limitation, however, is that PEG exhibits a well-known trans-trans-gauche to all-trans transition, which results in marked deviation from standard polymer elasticity models such as the worm-like chain, particularly at elevated forces. As a result, the assignment of unfolding events to protein domains based on their corresponding amino acid chain lengths is significantly obscured. Here, we provide a solution to this problem by implementing unstructured elastin-like polypeptides as linkers to replace PEG. We investigate the suitability of tailored elastin-like polypeptides linkers and perform direct comparisons to PEG, focusing on attributes that are critical for single-molecule force experiments such as linker length, monodispersity, and bioorthogonal conjugation tags. Our results demonstrate that by avoiding the ambiguous elastic response of mixed PEG/peptide systems and instead building the molecular mechanical systems with only a single bond type with uniform elastic properties, we improve data quality and facilitate data analysis and interpretation in force spectroscopy experiments. The use of all-peptide linkers allows alternative approaches for precisely defining elastic properties of proteins linked to surfaces.

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

Directory of Open Access Journals (Sweden)

Andrew R Schwendeman

Full Text Available 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.

Boosted Higgs boson tagging using jet substructures

CERN Document Server

Shvydkin, Pavel

2016-01-01

Searching BSM particles via the Higgs boson final state has now become common. The mass of desired BSM particle is more than 1 TeV, thereby its decay products are highly Lorentz-boosted. Hence the jets from b quark-antiquark pair - which the Higgs boson mostly decays into - are very closed to each other, and merged into one jet, that is typically reconstructed using large jet sizes (∆R = 0.8). In this work regression technique is applied to AK8 jets (which defined by anti-kT algorithm, using ΔR = 0.8). The regression makes use of boosted jets with substructure information, coupled with the pecularities of a b quark decay, like the presence of a soft lepton (SL) inside the jet. It has allowed to improve the resolution of the mass reconstruction and transverse momentum of the Higgs boson. This application results in improvement of the mass reconstruction by 3-4 percent. These result may be improved firstly by making more careful pileup rejection. Then it is possible to combine base regression train for dif...

New Developments for Jet Substructure Reconstruction in CMS

CERN Document Server

CMS Collaboration

2017-01-01

We present Monte Carlo based studies showcasing several developments for jet substructure reconstruction in CMS. This include Quark/Gluon tagging algorithms using Boosted Decision Trees and Deep Neural Networks, the XCone jet clustering algorithm and the Boosted Event Shape Tagger (BEST).

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

Science.gov (United States)

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

2017-11-15

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.

Towards an understanding of the correlations in jet substructure

Energy Technology Data Exchange (ETDEWEB)

Adams, D. [Brookhaven National Laboratory, Upton, NY (United States); Arce, A. [Duke University, Durham, NC (United States); Asquith, L. [University of Sussex, Brighton (United Kingdom); Backovic, M. [CP3, Universite catholique du Louvain, Louvain-la-Neuve (Belgium); Barillari, T.; Menke, S. [Max-Planck-Institute fuer Physik, Munich (Germany); Berta, P. [Charles University in Prague, FMP, Prague (Czech Republic); Bertolini, D. [University of California, Berkeley, CA (United States); Buckley, A.; Ferrando, J.; Pollard, C. [University of Glasgow, G12 8QQ (United Kingdom); Butterworth, J.; Cooper, B. [University College London, WC1E 6BT (United Kingdom); Camacho Toro, R.C.; Picazio, A. [University of Geneva, Geneva 4 (Switzerland); Caudron, J.; El Hedri, S.; Masetti, L. [Universitaet Mainz (Germany); Chien, Y.T.; Hornig, A.; Lee, C. [Los Alamos National Laboratory, Los Alamos, NM (United States); Cogan, J.; Nachman, B.; Nef, P.; Schwartzman, A.; Strauss, E.; Swiatlowski, M. [SLAC National Accelerator Laboratory, Menlo Park, CA (United States); Curtin, D. [University of Maryland, College Park, MD (United States); Debenedetti, C. [University of California, Santa Cruz, CA (United States); Dolen, J.; Rappoccio, S. [University at Buffalo, Buffalo, NY (United States); Eklund, M.; Embry, T.; Johns, K.; Lampl, W.; Leone, R.; Loch, P.; O' Grady, F.T.; Rutherfoord, J.; Veatch, J. [University of Arizona, Tucson, AZ (United States); Ellis, S.D. [University of Washington, Seattle, WA (United States); Ferencek, D. [Rutgers University, Piscataway, NJ (United States); Fleischmann, S. [Bergische Universitaet Wuppertal, Wuppertal (Germany); Freytsis, M.; Lopez Mateos, D.; Schwartz, M.D. [Harvard University, Cambridge, MA (United States); Giulini, M.; Sosa Corral, D.E. [Universitaet Heidelberg, Heidelberg (Germany); Han, Z.; Soper, D. [University of Oregon, Eugene, OR (United States); Hare, D.; Mishra, K.; Tran, N.V. [Fermi National Accelerator Laboratory, Batavia, IL (United States); Harris, P.; Potter-Landua, B.; Potter, C.; Thomas, C.; Young, C. [CERN, Geneva 23 (Switzerland); Hinzmann, A. [Universitaet Zuerich, Zurich (Switzerland); Hoing, R.; Kogler, R.; Marchesini, I.; Usai, E. [Universitaet Hamburg, Hamburg (Germany); Jankowiak, M. [New York University, New York, NY (United States); Kasieczka, G. [ETH Zuerich, Zurich (Switzerland); Larkoski, A.J.; Marzani, S.; Thaler, J. [Massachusetts Institute of Technology, Cambridge, MA (United States); Lou, H.K. [Princeton University, Princeton, NJ (United States); Low, M.; Miller, D.W. [University of Chicago, Zurich, IL (United States); Maksimovic, P. [Johns Hopkins University, Baltimore, MD (United States); McCarthy, R. [YITP, Stony Brook University, Stony Brook, NY (United States); Ovcharova, A. [University of California, Berkeley National Laboratory, Berkeley, CA (United States); Rojo, J.; Tseng, J. [University of Oxford, Oxford (United Kingdom); Salam, G.P. [CERN, Geneva 23 (Switzerland); LPTHE, UPMC Univ. Paris 6 and CNRS UMR, Paris (France); Schabinger, R.M. [Universidad Autonoma de Madrid, Madrid (Spain); Shuve, B. [Perimeter Institute for Theoretical Physics, ON (Canada); Sinervo, P. [University of Toronto, Toronto, ON (Canada); Spannowsky, M. [University of Durham, IPPP, Durham (United Kingdom); Thompson, E. [Columbia University, New York, NY (United States); Valery, L. [LPC Clermont-Ferrand, Aubiere Cedex (France); Vos, M. [Instituto de Fisica Corpuscular, IFIC/CSIC-UVEG, Valencia (Spain); Waalewijn, W. [University of Amsterdam, Amsterdam (Netherlands); Wacker, J. [Stanford Institute for Theoretical Physics, Stanford, CA (United States)

2015-09-15

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. (orig.)

Towards an understanding of the correlations in jet substructure

International Nuclear Information System (INIS)

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

2015-01-01

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. (orig.)

Power spectrum of dark matter substructure in strong gravitational lenses

Science.gov (United States)

Diaz Rivero, Ana; Cyr-Racine, Francis-Yan; Dvorkin, Cora

2018-01-01

Studying the smallest self-bound dark matter structure in our Universe can yield important clues about the fundamental particle nature of dark matter. Galaxy-scale strong gravitational lensing provides a unique way to detect and characterize dark matter substructures at cosmological distances from the Milky Way. Within the cold dark matter (CDM) paradigm, the number of low-mass subhalos within lens galaxies is expected to be large, implying that their contribution to the lensing convergence field is approximately Gaussian and could thus be described by their power spectrum. We develop here a general formalism to compute from first principles the substructure convergence power spectrum for different populations of dark matter subhalos. As an example, we apply our framework to two distinct subhalo populations: a truncated Navarro-Frenk-White subhalo population motivated by standard CDM, and a truncated cored subhalo population motivated by self-interacting dark matter (SIDM). We study in detail how the subhalo abundance, mass function, internal density profile, and concentration affect the amplitude and shape of the substructure power spectrum. We determine that the power spectrum is mostly sensitive to a specific combination of the subhalo abundance and moments of the mass function, as well as to the average tidal truncation scale of the largest subhalos included in the analysis. Interestingly, we show that the asymptotic slope of the substructure power spectrum at large wave number reflects the internal density profile of the subhalos. In particular, the SIDM power spectrum exhibits a characteristic steepening at large wave number absent in the CDM power spectrum, opening the possibility of using this observable, if at all measurable, to discern between these two scenarios.

Structural properties of the linkers connecting the N- and C- terminal domains in the MocR bacterial transcriptional regulators

Directory of Open Access Journals (Sweden)

Teresa Milano

2016-12-01

Full Text Available Peptide inter-domain linkers are peptide segments covalently linking two adjacent domains within a protein. Linkers play a variety of structural and functional roles in naturally occurring proteins. In this work we analyze the sequence properties of the predicted linker regions of the bacterial transcriptional regulators belonging to the recently discovered MocR subfamily of the GntR regulators. Analyses were carried out on the MocR sequences taken from the phyla Actinobacteria, Firmicutes, Alpha-, Beta- and Gammaproteobacteria. The results suggest that MocR linkers display phylum-specific characteristics and unique features different from those already described for other classes of inter-domain linkers. They show an average length significantly higher: 31.8 ± 14.3 residues reaching a maximum of about 150 residues. Compositional propensities displayed general and phylum-specific trends. Pro is dominating in all linkers. Dyad propensity analysis indicate Pro–Pro as the most frequent amino acid pair in all linkers. Physicochemical properties of the linker regions were assessed using amino acid indices relative to different features: in general, MocR linkers are flexible, hydrophilic and display propensity for β-turn or coil conformations. Linker sequences are hypervariable: only similarities between MocR linkers from organisms related at the level of species or genus could be found with sequence searches. The results shed light on the properties of the linker regions of the new MocR subfamily of bacterial regulators and may provide knowledge-based rules for designing artificial linkers with desired properties.

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

Energy Technology Data Exchange (ETDEWEB)

Andrews, Sean M.; Wilner, David J.; Bai, Xue-Ning; Öberg, Karin I.; Ricci, Luca [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Zhu, Zhaohuan [Department of Astrophysical Sciences, Princeton University, 4 Ivy Lane, Peyton Hall, Princeton, NJ 08544 (United States); Birnstiel, Tilman [Max-Planck-Institut für Astronomie, Königstuhl 17, D-69117 Heidelberg (Germany); Carpenter, John M. [Joint ALMA Observatory (JAO), Alonso de Cordova 3107, Vitacura-Santiago de Chile (Chile); Pérez, Laura M. [Max-Planck-Institut für Radioastronomie, Auf dem Hügel 69, D-53121 Bonn (Germany); Hughes, A. Meredith [Department of Astronomy, Wesleyan University, Van Vleck Observatory, 96 Foss Hill Drive, Middletown, CT 06457 (United States); Isella, Andrea, E-mail: sandrews@cfa.harvard.edu [Department of Physics and Astronomy, Rice University, 6100 Main Street, Houston, TX 77005 (United States)

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.

Linker-dependent Junction Formation Probability in Single-Molecule Junctions

Energy Technology Data Exchange (ETDEWEB)

Yoo, Pil Sun; Kim, Taekyeong [HankukUniversity of Foreign Studies, Yongin (Korea, Republic of)

2015-01-15

We compare the junction formation probabilities of single-molecule junctions with different linker molecules by using a scanning tunneling microscope-based break-junction technique. We found that the junction formation probability varies as SH > SMe > NH2 for the benzene backbone molecule with different types of anchoring groups, through quantitative statistical analysis. These results are attributed to different bonding forces according to the linker groups formed with Au atoms in the electrodes, which is consistent with previous works. Our work allows a better understanding of the contact chemistry in the metal.molecule junction for future molecular electronic devices.

Performance of Jet Substructure Techniques and Boosted Object Identification in ATLAS

CERN Document Server

Lacey, J; The ATLAS collaboration

2014-01-01

ATLAS has implemented and commissioned many new jet substructure techniques to aid in the identification and interpretation of hadronic final states originating from Lorentz-boosted heavy particles produced at the LHC. These techniques include quantum jets, jet charge, jet shapes, quark/gluon, boosted boson and top quark tagging, along with grooming methods such as pruning, trimming, and filtering. These techniques have been validated using the large 2012 ATLAS dataset. Presented here is a summary of the state of the art jet substructure and tagging techniques developed in ATLAS, their performance and recent results.

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

Energy Technology Data Exchange (ETDEWEB)

Ichida, Yu, E-mail: ichida-y@ncchd.go.jp; 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.

Effect of Soil-Structure Interaction on Seismic Performance of Long-Span Bridge Tested by Dynamic Substructuring Method

Directory of Open Access Journals (Sweden)

Zhenyun Tang

2017-01-01

Full Text Available Because of the limitations of testing facilities and techniques, the seismic performance of soil-structure interaction (SSI system can only be tested in a quite small scale model in laboratory. Especially for long-span bridge, a smaller tested model is required when SSI phenomenon is considered in the physical test. The scale effect resulting from the small scale model is always coupled with the dynamic performance, so that the seismic performance of bridge considering SSI effect cannot be uncovered accurately by the traditional testing method. This paper presented the implementation of real-time dynamic substructuring (RTDS, involving the combined use of shake table array and computational engines for the seismic simulation of SSI. In RTDS system, the bridge with soil-foundation system is divided into physical and numerical substructures, in which the bridge is seen as physical substructures and the remaining part is seen as numerical substructures. The interface response between the physical and numerical substructures is imposed by shake table and resulting reaction force is fed back to the computational engine. The unique aspect of the method is to simulate the SSI systems subjected to multisupport excitation in terms of a larger physical model. The substructuring strategy and the control performance associated with the real-time substructuring testing for SSI were performed. And the influence of SSI on a long-span bridge was tested by this novel testing method.

Revealing dark matter substructure with anisotropies in the diffuse gamma-ray background

OpenAIRE

Siegal-Gaskins, Jennifer M.

2008-01-01

The majority of gamma-ray emission from Galactic dark matter annihilation is likely to be detected as a contribution to the diffuse gamma-ray background. I show that dark matter substructure in the halo of the Galaxy induces characteristic anisotropies in the diffuse background that could be used to determine the small-scale dark matter distribution. I calculate the angular power spectrum of the emission from dark matter substructure for several models of the subhalo population, and show that...

Investigation Of Failure Mechanisms In A Wind Turbine Blade Root Sub-Structure

DEFF Research Database (Denmark)

Bender, Jens Jakob; Hallett, S.R.; Lindgaard, Esben

2017-01-01

and realistic results at the fraction of the cost of a full-scale test. Therefore, this work focuses on testing of sub-structures from the root end of wind turbine blades at the transition from the thick root laminate to the thinner main laminate. Some wind turbine blade manufacturers include pre-cured tapered...... beams in the root to reduce the time required to place the large quantity of material in the mould and to decrease manufacturing defects in these elements. However, this entails the risk of introducing other manufacturing defects during the Vacuum Assisted Resin Transfer Moulding process such as resin...... pockets and fibre wrinkles. Through this work it is sought to determine the effect that these manufacturing defects can have on the strength properties of the sub-structure. The sub-structures used in this work are cut out from actual wind turbine blades, meaning that the manufacturing defects...

Mixed-linker zeolitic imidazolate framework mixed-matrix membranes for aggressive CO2 separation from natural gas

KAUST Repository

Thompson, Joshua A.

2014-07-01

Zeolitic imidazolate framework (ZIF) materials are a promising subclass of metal-organic frameworks (MOF) for gas separations. However, due to the deleterious effects of gate-opening phenomena associated with organic linker rotation near the limiting pore apertures of ZIFs, there have been few demonstrations of improved gas separation properties over pure polymer membranes when utilizing ZIF materials in composite membranes for CO2-based gas separations. Here, we report a study of composite ZIF/polymer membranes, containing mixed-linker ZIF materials with ZIF-8 crystal topologies but composed of different organic linker compositions. Characterization of the mixed-linker ZIFs shows that the mixed linker approach offers control over the porosity and pore size distribution of the materials, as determined from nitrogen physisorption and Horváth-Kawazoe analysis. Single gas permeation measurements on mixed-matrix membranes reveal that inclusion of mixed-linker ZIFs yields membranes with better ideal CO2/CH4 selectivity than membranes containing ZIF-8. This improvement is shown to likely occur from enhancement in the diffusion selectivity of the membranes associated with controlling the pore size distribution of the ZIF filler. Mixed-gas permeation experiments show that membranes with mixed-linker ZIFs display an effective plasticization resistance that is not typical of the pure polymeric matrix. Overall, we demonstrate that mixed-linker ZIFs can improve the gas separation properties in composite membranes and may be applicable to aggressive CO2 concentrations in natural gas feeds. © 2013 Elsevier Inc. All rights reserved.

The Abl SH2-kinase linker naturally adopts a conformation competent for SH3 domain binding.

Science.gov (United States)

Chen, Shugui; Brier, Sébastien; Smithgall, Thomas E; Engen, John R

2007-04-01

The core of the Abelson tyrosine kinase (c-Abl) is structurally similar to Src-family kinases where SH3 and SH2 domains pack against the backside of the kinase domain in the down-regulated conformation. Both kinase families depend upon intramolecular association of SH3 with the linker joining the SH2 and kinase domains for suppression of kinase activity. Hydrogen deuterium exchange (HX) and mass spectrometry (MS) were used to probe intramolecular interaction of the c-Abl SH3 domain with the linker in recombinant constructs lacking the kinase domain. Under physiological conditions, the c-Abl SH3 domain undergoes partial unfolding, which is stabilized by ligand binding, providing a unique assay for SH3:linker interaction in solution. Using this approach, we observed dynamic association of the SH3 domain with the linker in the absence of the kinase domain. Truncation of the linker before W254 completely prevented cis-interaction with SH3, while constructs containing amino acids past this point showed SH3:linker interactions. The observation that the Abl linker sequence exhibits SH3-binding activity in the absence of the kinase domain is unique to Abl and was not observed with Src-family kinases. These results suggest that SH3:linker interactions may have a more prominent role in Abl regulation than in Src kinases, where the down-regulated conformation is further stabilized by a second intramolecular interaction between the C-terminal tail and the SH2 domain.

A composite experimental dynamic substructuring method based on partitioned algorithms and localized Lagrange multipliers

Science.gov (United States)

Abbiati, Giuseppe; La Salandra, Vincenzo; Bursi, Oreste S.; Caracoglia, Luca

2018-02-01

Successful online hybrid (numerical/physical) dynamic substructuring simulations have shown their potential in enabling realistic dynamic analysis of almost any type of non-linear structural system (e.g., an as-built/isolated viaduct, a petrochemical piping system subjected to non-stationary seismic loading, etc.). Moreover, owing to faster and more accurate testing equipment, a number of different offline experimental substructuring methods, operating both in time (e.g. the impulse-based substructuring) and frequency domains (i.e. the Lagrange multiplier frequency-based substructuring), have been employed in mechanical engineering to examine dynamic substructure coupling. Numerous studies have dealt with the above-mentioned methods and with consequent uncertainty propagation issues, either associated with experimental errors or modelling assumptions. Nonetheless, a limited number of publications have systematically cross-examined the performance of the various Experimental Dynamic Substructuring (EDS) methods and the possibility of their exploitation in a complementary way to expedite a hybrid experiment/numerical simulation. From this perspective, this paper performs a comparative uncertainty propagation analysis of three EDS algorithms for coupling physical and numerical subdomains with a dual assembly approach based on localized Lagrange multipliers. The main results and comparisons are based on a series of Monte Carlo simulations carried out on a five-DoF linear/non-linear chain-like systems that include typical aleatoric uncertainties emerging from measurement errors and excitation loads. In addition, we propose a new Composite-EDS (C-EDS) method to fuse both online and offline algorithms into a unique simulator. Capitalizing from the results of a more complex case study composed of a coupled isolated tank-piping system, we provide a feasible way to employ the C-EDS method when nonlinearities and multi-point constraints are present in the emulated system.

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

Science.gov (United States)

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.

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

DEFF Research Database (Denmark)

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

2016-01-01

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...

Chemical substructure analysis in toxicology

Energy Technology Data Exchange (ETDEWEB)

Beauchamp, R.O. Jr. [Center for Information on Toxicology and Environment, Raleigh, NC (United States)

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.

Description of a cellulose-binding domain and a linker sequence from Aspergillus fungi

NARCIS (Netherlands)

Quentin, M; Ebbelaar, M; Derksen, J; Mariani, C; van der Valk, H

A family I cellulose-binding domain (CBD) and a serine- and threonine-rich linker peptide were cloned from the fungi Aspergillus japonicus and Aspergillus aculeatus. A glutathione S-transferase (GST) fusion protein comprising GST and a peptide linker with the CBD fused to its C-terminus, was

Two innovative solutions based on fibre concrete blocks designed for building substructure

Science.gov (United States)

Pazderka, J.; Hájek, P.

2017-09-01

Using of fibers in a high-strength concrete allows reduction of the dimensions of small precast concrete elements, which opens up new ways of solution for traditional construction details in buildings. The paper presents two innovative technical solutions for building substructure: The special shaped plinth block from fibre concrete and the fibre concrete elements for new technical solution of ventilated floor. The main advantages of plinth block from fibre concrete blocks (compared with standard plinth solutions) is: easier and faster assembly, higher durability and thanks to the air cavity between the vertical part of the block, the building substructure reduced moisture level of structures under the waterproofing layer and a comprehensive solution to the final surface of building plinth as well as the surface of adjacent terrain. The ventilated floor based on fibre concrete precast blocks is an attractive structural alternative for tackling the problem of increased moisture in masonry in older buildings, lacking a functional waterproof layer in the substructure.

Earthquake analysis of structures including structure-soil interaction by a substructure method

International Nuclear Information System (INIS)

Chopra, A.K.; Guttierrez, J.A.

1977-01-01

A general substructure method for analysis of response of nuclear power plant structures to earthquake ground motion, including the effects of structure-soil interaction, is summarized. The method is applicable to complex structures idealized as finite element systems and the soil region treated as either a continuum, for example as a viscoelastic halfspace, or idealized as a finite element system. The halfspace idealization permits reliable analysis for sites where essentially similar soils extend to large depths and there is no rigid boundary such as soil-rock interface. For sites where layers of soft soil are underlain by rock at shallow depth, finite element idealization of the soil region is appropriate; in this case, the direct and substructure methods would lead to equivalent results but the latter provides the better alternative. Treating the free field motion directly as the earthquake input in the substructure eliminates the deconvolution calculations and the related assumption-regarding type and direction of earthquake waves-required in the direct method. (Auth.)

Improving jet substructure performance in ATLAS with unified tracking and calorimeter inputs

CERN Document Server

Jansky, Roland; The ATLAS collaboration

2018-01-01

Jet substructure techniques play a critical role in ATLAS in searches for new physics, and are being utilized in the trigger. They become increasingly important in detailed studies of the Standard Model, among them the inclusive search for the Higgs boson produced with high transverse momentum decaying to a bottom-antibottom quark pair. To date, ATLAS has mostly focused on the use of calorimeter-based jet substructure, which works well for jets initiated by particles with low to moderate boost, but which lacks the angular resolution needed to resolve the desired substructure in the highly-boosted regime. We will present a novel approach designed to mitigate the calorimeter angular resolution limitations, thus providing superior performance to prior methods. Similar to previous methods, the superior angular resolution of the tracker is combined with information from the calorimeters. However, the new method is fundamentally different, as it correlates low-level objects as tracks and individual energy deposits ...

Jet Substructure Measurements Sensitive to Soft QCD effects with the ATLAS Detector

CERN Document Server

Asquith, Lily; The ATLAS collaboration

2017-01-01

Calculations of jet substructure observables which are accurate beyond leading-logarithmic accuracy have recently become available. Such observables are significant not only for probing a new regime of QCD at a hadron collider, but also for improving the understanding of jet substructure properties that are used in many studies at the Large Hadron Collider. In this talk, we discuss first measurement of jet substructure quantities at a hadron collider, calculated at next-to-next-to-leading-logarithm accuracy. The soft drop mass is measured in dijet events with the ATLAS detector at 13 TeV, unfolded to particle-level and compared to Monte Carlo simulations. In addition, we present a measurement of the splitting scales in the kt jet-clustering algorithm for final states containing a Z-boson candidate at a centre-of-mass energy of 8 TeV.  The data are also corrected for detector effects and are compared to state-of-the-art Monte Carlo predictions.

Residuated lattices an algebraic glimpse at substructural logics

CERN Document Server

Galatos, Nikolaos; Kowalski, Tomasz; Ono, Hiroakira

2007-01-01

The book is meant to serve two purposes. The first and more obvious one is to present state of the art results in algebraic research into residuated structures related to substructural logics. The second, less obvious but equally important, is to provide a reasonably gentle introduction to algebraic logic. At the beginning, the second objective is predominant. Thus, in the first few chapters the reader will find a primer of universal algebra for logicians, a crash course in nonclassical logics for algebraists, an introduction to residuated structures, an outline of Gentzen-style calculi as well as some titbits of proof theory - the celebrated Hauptsatz, or cut elimination theorem, among them. These lead naturally to a discussion of interconnections between logic and algebra, where we try to demonstrate how they form two sides of the same coin. We envisage that the initial chapters could be used as a textbook for a graduate course, perhaps entitled Algebra and Substructural Logics. As the book progresses the f...

Influence of solidification parameters on the cellular sub-structure of tin and some tin alloys

International Nuclear Information System (INIS)

Milosavljevic, Dj.

1965-01-01

This paper describes an attempt to obtain qualitative data on sub-structure of samples solidified in contact with the cooler. The objective of experiments was to study micro segregation phenomena by investigating the substructure in the solidified sample obtained under experimental conditions which are similar to real solidification conditions

The End-Of-Substructure Card for the ATLAS ITk Strip Tracker

CERN Document Server

Goettlicher, Peter; The ATLAS collaboration

2018-01-01

The End-Of-Substructure Card (EoS) is the interface between the building block of the ITk Strip Tracker (staves and petals) and the outside world. In the ITk the modules consisting of the silicon sensor itself and the hybrids with the readout ASICS are placed on a common structure called a stave (in the barrel) and petal (in the end-cap). All module use a common bus-tape co-cured to carbon-fiber based structure to distribute power and signals. The data lines and command lines are then connected from the bus-tape to EoS. The power, both low and high voltage, are also distributed via the bus tape and coonected to the EoS. All these connections will be made using wire-bonds. The card concept is build around using the lpGBT chip set and the VTRx optical link, both common developments for the LHC Upgrades. The command signals will be coming in on a 10 Gbit/s link and will be de-multiplexed by the lpGBt and send to the stave/petal. The incoming data from the sensor, which depending on the type of stave or petal wil...

High-Flux Zeolitic Imidazolate Framework Membranes for Propylene/Propane Separation by Postsynthetic Linker Exchange.

Science.gov (United States)

Lee, Moon Joo; Kwon, Hyuk Taek; Jeong, Hae-Kwon

2018-01-02

While zeolitic imidazolate framework, ZIF-8, membranes show impressive propylene/propane separation, their throughput needs to be greatly improved for practical applications. A method is described that drastically reduces the effective thickness of ZIF-8 membranes, thereby substantially improving their propylene permeance (that is, flux). The new strategy is based on a controlled single-crystal to single-crystal linker exchange of 2-methylimidazole in ZIF-8 membrane grains with 2-imidazolecarboxaldehyde (ZIF-90 linker), thereby enlarging the effective aperture size of ZIF-8. The linker-exchanged ZIF-8 membranes showed a drastic increase in propylene permeance by about four times, with a negligible loss in propylene/propane separation factor when compared to as-prepared membranes. The linker-exchange effect depends on the membrane synthesis method. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rapid construction of mechanically- confined multi- cellular structures using dendrimeric intercellular linker.

Science.gov (United States)

Mo, Xuejun; Li, Qiushi; Yi Lui, Lena Wai; Zheng, Baixue; Kang, Chiang Huen; Nugraha, Bramasta; Yue, Zhilian; Jia, Rui Rui; Fu, Hong Xia; Choudhury, Deepak; Arooz, Talha; Yan, Jie; Lim, Chwee Teck; Shen, Shali; Hong Tan, Choon; Yu, Hanry

2010-10-01

Tissue constructs that mimic the in vivo cell-cell and cell-matrix interactions are especially useful for applications involving the cell- dense and matrix- poor internal organs. Rapid and precise arrangement of cells into functional tissue constructs remains a challenge in tissue engineering. We demonstrate rapid assembly of C3A cells into multi- cell structures using a dendrimeric intercellular linker. The linker is composed of oleyl- polyethylene glycol (PEG) derivatives conjugated to a 16 arms- polypropylenimine hexadecaamine (DAB) dendrimer. The positively charged multivalent dendrimer concentrates the linker onto the negatively charged cell surface to facilitate efficient insertion of the hydrophobic oleyl groups into the cellular membrane. Bringing linker- treated cells into close proximity to each other via mechanical means such as centrifugation and micromanipulation enables their rapid assembly into multi- cellular structures within minutes. The cells exhibit high levels of viability, proliferation, three- dimensional (3D) cell morphology and other functions in the constructs. We constructed defined multi- cellular structures such as rings, sheets or branching rods that can serve as potential tissue building blocks to be further assembled into complex 3D tissue constructs for biomedical applications. 2010 Elsevier Ltd. All rights reserved.

Effect of linkers on the αvβ3 integrin targeting efficiency of cyclic RGD-conjugates

Science.gov (United States)

Karmakar, Partha; Grabowska, Dorota; Sudlow, Gail; Ziabrev, Kostiantyn; Sanyal, Nibedita; Achilefu, Samuel

2018-02-01

Cyclic arginine-glycine-aspartic acid (cRGD) peptides are well known to target ανβ3 integrin expressed on cancer cells and neovasculature. Conjugation of these peptides with dyes, drugs, antibodies and other biomolecules through covalent linkers provides a facile way to deliver these products to tumor cells for targeted cancer therapy and diagnosis. Click chemistry and acid-amine couplings are widely used conjugation strategies. However, the effects of different linkers and the distance between the cRGD and the conjugates on the binding of cRGD ligand with ανβ3 has been underexplored. In this present study, we prepared cRGD-conjugates using different linkers and determined how they altered the tumor targeting efficiency in vitro and in vivo. The results demonstrate that different linkers significantly altered the pharmacokinetics of the cRGD conjugates and the tumor uptake kinetics. Unlike large antibodies, this preliminary finding shows that linkers used to attach drugs and fluorescent molecular probes to small peptides play a major role in the accuracy of tumor targeting and treatment outcomes. As a result, considerable attention should be paid to the nature of linkers used in the design of molecular probes and targeted therapeutics.

Replaceable Substructures for Efficient Part-Based Modeling

KAUST Repository

Liu, Han; Vimont, Ulysse; Wand, Michael; Cani, Marie Paule; Hahmann, Stefanie; Rohmer, Damien; Mitra, Niloy J.

2015-01-01

A popular mode of shape synthesis involves mixing and matching parts from different objects to form a coherent whole. The key challenge is to efficiently synthesize shape variations that are plausible, both locally and globally. A major obstacle is to assemble the objects with local consistency, i.e., all the connections between parts are valid with no dangling open connections. The combinatorial complexity of this problem limits existing methods in geometric and/or topological variations of the synthesized models. In this work, we introduce replaceable substructures as arrangements of parts that can be interchanged while ensuring boundary consistency. The consistency information is extracted from part labels and connections in the original source models. We present a polynomial time algorithm that discovers such substructures by working on a dual of the original shape graph that encodes inter-part connectivity. We demonstrate the algorithm on a range of test examples producing plausible shape variations, both from a geometric and from a topological viewpoint. © 2015 The Author(s) Computer Graphics Forum © 2015 The Eurographics Association and John Wiley & Sons Ltd. Published by John Wiley & Sons Ltd.

Replaceable Substructures for Efficient Part-Based Modeling

KAUST Repository

Liu, Han

2015-05-01

A popular mode of shape synthesis involves mixing and matching parts from different objects to form a coherent whole. The key challenge is to efficiently synthesize shape variations that are plausible, both locally and globally. A major obstacle is to assemble the objects with local consistency, i.e., all the connections between parts are valid with no dangling open connections. The combinatorial complexity of this problem limits existing methods in geometric and/or topological variations of the synthesized models. In this work, we introduce replaceable substructures as arrangements of parts that can be interchanged while ensuring boundary consistency. The consistency information is extracted from part labels and connections in the original source models. We present a polynomial time algorithm that discovers such substructures by working on a dual of the original shape graph that encodes inter-part connectivity. We demonstrate the algorithm on a range of test examples producing plausible shape variations, both from a geometric and from a topological viewpoint. © 2015 The Author(s) Computer Graphics Forum © 2015 The Eurographics Association and John Wiley & Sons Ltd. Published by John Wiley & Sons Ltd.

VARIATION OF SUBSTRUCTURES OF PEARLITIC HEAT RESISTANT STEEL AFTER HIGH TEMPERATURE AGING

Institute of Scientific and Technical Information of China (English)

R.C.Yang; K.Chen; H.X.Feng; H.Wang

2004-01-01

The observations of dislocations, substructures and other microstructural details were conducted mainly by means of transmission electron microscope (TEM) and scanning electron microscope (SEM) for 12Cr1Mo V pearlitic heat-resistant steel. It is shown that during the high temperature long-term aging, the disordered and jumbled phasetransformed dislocations caused by normalized cooling are recovered and rearranged into cell substructures, and then the dislocation density is reduced gradually. Finally a low density linear dislocation configuration and a stabler dislocation network are formed and ferritic grains grow considerably.

Structure and substructure analysis of DAFT/FADA galaxy clusters in the [0.4-0.9] redshift range

Science.gov (United States)

Guennou, L.; Adami, C.; Durret, F.; Lima Neto, G. B.; Ulmer, M. P.; Clowe, D.; LeBrun, V.; Martinet, N.; Allam, S.; Annis, J.; Basa, S.; Benoist, C.; Biviano, A.; Cappi, A.; Cypriano, E. S.; Gavazzi, R.; Halliday, C.; Ilbert, O.; Jullo, E.; Just, D.; Limousin, M.; Márquez, I.; Mazure, A.; Murphy, K. J.; Plana, H.; Rostagni, F.; Russeil, D.; Schirmer, M.; Slezak, E.; Tucker, D.; Zaritsky, D.; Ziegler, B.

2014-01-01

Context. The DAFT/FADA survey is based on the study of ~90 rich (masses found in the literature >2 × 1014 M⊙) and moderately distant clusters (redshifts 0.4 DAFT/FADA survey for which XMM-Newton and/or a sufficient number of galaxy redshifts in the cluster range are available, with the aim of detecting substructures and evidence for merging events. These properties are discussed in the framework of standard cold dark matter (ΛCDM) cosmology. Methods: In X-rays, we analysed the XMM-Newton data available, fit a β-model, and subtracted it to identify residuals. We used Chandra data, when available, to identify point sources. In the optical, we applied a Serna & Gerbal (SG) analysis to clusters with at least 15 spectroscopic galaxy redshifts available in the cluster range. We discuss the substructure detection efficiencies of both methods. Results: XMM-Newton data were available for 32 clusters, for which we derive the X-ray luminosity and a global X-ray temperature for 25 of them. For 23 clusters we were able to fit the X-ray emissivity with a β-model and subtract it to detect substructures in the X-ray gas. A dynamical analysis based on the SG method was applied to the clusters having at least 15 spectroscopic galaxy redshifts in the cluster range: 18 X-ray clusters and 11 clusters with no X-ray data. The choice of a minimum number of 15 redshifts implies that only major substructures will be detected. Ten substructures were detected both in X-rays and by the SG method. Most of the substructures detected both in X-rays and with the SG method are probably at their first cluster pericentre approach and are relatively recent infalls. We also find hints of a decreasing X-ray gas density profile core radius with redshift. Conclusions: The percentage of mass included in substructures was found to be roughly constant with redshift values of 5-15%, in agreement both with the general CDM framework and with the results of numerical simulations. Galaxies in substructures

The centrosomal linker and microtubules provide dual levels of spatial coordination of centrosomes.

Directory of Open Access Journals (Sweden)

Marko Panic

2015-05-01

Full Text Available 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.

Linker Histone Phosphorylation Regulates Global Timing of Replication Origin Firing*S⃞

Science.gov (United States)

Thiriet, Christophe; Hayes, Jeffrey J.

2009-01-01

Despite the presence of linker histone in all eukaryotes, the primary function(s) of this histone have been difficult to clarify. Knock-out experiments indicate that H1s play a role in regulation of only a small subset of genes but are an essential component in mouse development. Here, we show that linker histone (H1) is involved in the global regulation of DNA replication in Physarum polycephalum. We find that genomic DNA of H1 knock-down cells is more rapidly replicated, an effect due at least in part to disruption of the native timing of replication fork firing. Immunoprecipitation experiments demonstrate that H1 is transiently lost from replicating chromatin via a process facilitated by phosphorylation. Our results suggest that linker histones generate a chromatin environment refractory to replication and that their transient removal via protein phosphorylation during S phase is a critical step in the epigenetic regulation of replication timing. PMID:19015270

Specific distribution of the Saccharomyces cerevisiae linker histone homolog HHO1p in the chromatin

OpenAIRE

Freidkin, Ilya; Katcoff, Don J.

2001-01-01

In virtually all eukaryotic organisms, linker DNA between nucleosomes is associated with a histone termed linker histone or histone H1. In Saccharomyces cerevisiae, HHO1 encodes a putative linker histone with very significant homology to histone H1. The encoded protein is expressed in the nucleus, but has not been shown to affect global chromatin structure, nor has its deletion shown any detectable phenotype. In vitro chromatin assembly experiments with recombinant HHO1p have shown that it is...

The LabelHash algorithm for substructure matching

Directory of Open Access Journals (Sweden)

Bryant Drew H

2010-11-01

Full Text Available Abstract Background There is an increasing number of proteins with known structure but unknown function. Determining their function would have a significant impact on understanding diseases and designing new therapeutics. However, experimental protein function determination is expensive and very time-consuming. Computational methods can facilitate function determination by identifying proteins that have high structural and chemical similarity. Results We present LabelHash, a novel algorithm for matching substructural motifs to large collections of protein structures. The algorithm consists of two phases. In the first phase the proteins are preprocessed in a fashion that allows for instant lookup of partial matches to any motif. In the second phase, partial matches for a given motif are expanded to complete matches. The general applicability of the algorithm is demonstrated with three different case studies. First, we show that we can accurately identify members of the enolase superfamily with a single motif. Next, we demonstrate how LabelHash can complement SOIPPA, an algorithm for motif identification and pairwise substructure alignment. Finally, a large collection of Catalytic Site Atlas motifs is used to benchmark the performance of the algorithm. LabelHash runs very efficiently in parallel; matching a motif against all proteins in the 95% sequence identity filtered non-redundant Protein Data Bank typically takes no more than a few minutes. The LabelHash algorithm is available through a web server and as a suite of standalone programs at http://labelhash.kavrakilab.org. The output of the LabelHash algorithm can be further analyzed with Chimera through a plugin that we developed for this purpose. Conclusions LabelHash is an efficient, versatile algorithm for large-scale substructure matching. When LabelHash is running in parallel, motifs can typically be matched against the entire PDB on the order of minutes. The algorithm is able to identify

Galactic densities, substructure and the initial power spectrum

International Nuclear Information System (INIS)

Bullock, J.S.; Zentner, A.R.

2003-01-01

Although the currently favored cold dark matter plus cosmological constant model for structure formation assumes an n = 1 scale-invariant initial power spectrum, most inflation models produce at least mild deviations from n = 1. Because the lever arm from the CMB normalization to galaxy scales is long, even a small 'tilt' can have important implications for galactic observations. Here we calculate the COBS-normalized power spectra for several well-motivated models of inflation and compute implications for the substructure content and central densities of galaxy halos. Using an analytic model, normalized against N-body simulations, we show that while halos in the standard (n = 1) model are overdense by a factor of ∼ 6 compared to observations, several of our example inflation+LCDM models predict halo densities well within the range of observations, which prefer models with n ∼ 0.85. We go on to use a semi-analytic model (also normalized against N-body simulations) to follow the merger histories of galaxy-sized halos and track the orbital decay, disruption, and evolution of the merging substructure. Models with n ∼ 0.85 predict a factor of ∼ 3 fewer subhalos at a fixed circular velocity than the standard n 1 case. Although this level of reduction does not resolve the 'dwarf satellite problem', it does imply that the level of feedback required to match the observed number of dwarfs is sensitive to the initial power spectrum. Finally, the fraction of galaxy-halo mass that is bound up in substructure is consistent with limits imposed by multiply imaged quasars for all models considered: f sat > 0.01 even for an effective tilt of n ∼ 0.8. We conclude that, at their current level, lensing constraints of this kind do not provide an interesting probe of the primordial power spectrum

The angular power spectrum of the diffuse gamma-ray background as a probe of Galactic dark matter substructure

OpenAIRE

Siegal-Gaskins, Jennifer M.

2009-01-01

Dark matter annihilation in Galactic substructure produces diffuse gamma-ray emission of remarkably constant intensity across the sky, and in general this signal dominates over the smooth halo signal at angles greater than a few tens of degrees from the Galactic Center. The large-scale isotropy of the emission from substructure suggests that it may be difficult to extract this Galactic dark matter signal from the extragalactic gamma-ray background. I show that dark matter substructure induces...

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

Science.gov (United States)

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

On mechanism of substructure formation in SmS during isomorphic phase transformations

International Nuclear Information System (INIS)

Aptekar', I.L.; Ivanov, V.I.; Tonkov, E.Yu.; Shmyt'ko, I.M.

1986-01-01

X-ray diffraction study of substructure characteristics of SmS samples subjected to treatment at different temrerature and pressure in media with different viscosity ( graphite, silicon oil) for realization of P-M-P transformations ( p-semiconductor phase, M - high pressure phase) is performed. It is assumed that with M - phase formation P - matrix volume relaxation delays, therefore the new phase particles occupy smaller volume than the initial matrix which causes the M - phase disorientation. The difference between the phase transformation rate and deformation rate under the pressure in media with various viscosity results in arising different substructural characteristics

The flexibility of modified-linker MIL-53 materials.

Science.gov (United States)

Munn, Alexis S; Pillai, Renjith S; Biswas, Shyam; Stock, Norbert; Maurin, Guillaume; Walton, Richard I

2016-03-14

The flexibility of eight aluminium hydroxo terephthalates [Al(OH)(BDC-X)]·n(guest) (BDC = 1,4-benzene-dicarboxylate; X = -H, -CH3, -Cl, -Br, -NH2, -NO2, -(OH)2, -CO2H) crystallising in the MIL-53-type structure was investigated upon thermal dehydration of as-made samples, superhydration and methanol adsorption/desorption using in situ powder X-ray diffraction (PXRD). Profile fitting was used to determine lattice parameters as a function of time and/or temperature to describe their structural evolution. It has thus been shown that while methanol vapour adsorption induces an opening of all the modified frameworks, except the -NH2 material, superhydration only leads to open structures for Al-MIL-53-NO2, -Br and -(OH)2. All the MIL-53 solids, except Al-MIL-53-(OH)2 are present in the open structures upon thermal dehydration. In addition to the exploration of the breathing behavior of this MIL-53 series, the issue of disorder in the distribution of the functional groups between the organic linkers was explored. As a typical illustration, density functional theory calculations were carried out on different structures of Al-MIL-53-Cl, in which the distribution of -Cl within two adjacent BDC linkers is varied. The results show that the most energetically stable configuration leads to the best agreement with the experimental PXRD pattern. This observation supports that the distribution of the selected linker substituent in the functionalised solid is governed by energetics and that there is a preference for an ordering of this arrangement.

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

Energy Technology Data Exchange (ETDEWEB)

Gwinn, C. R. [Physics Department, Broida Hall, University of California, Santa Barbara, CA 93117 (United States); Kovalev, Y. Y.; Soglasnov, V. A. [Astro Space Center, Lebedev Physical Institute, Russian Academy of Sciences, Profsoyuznaya Str. 84/32, Moscow 117997 (Russian Federation); Johnson, M. D., E-mail: cgwinn@physics.ucsb.edu [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States)

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.

Rapid One-Pot Microwave Synthesis of Mixed-Linker Hybrid Zeolitic-Imidazolate Framework Membranes for Tunable Gas Separations.

Science.gov (United States)

Hillman, Febrian; Brito, Jordan; Jeong, Hae-Kwon

2018-02-14

The relatively slow and complex fabrication processes of polycrystalline metal-organic framework (MOF) membranes often times restrict their way to commercialization, despite their potential for molecular separation applications. Herein, we report a rapid one-pot microwave synthesis of mixed-linker hybrid zeolitic-imidazolate framework (ZIF) membranes consisting of 2-methylimidazolate (ZIF-8 linker) and benzimidazolate (ZIF-7 linker) linkers, termed ZIF-7-8 membranes. The fast-volumetric microwave heating in conjunction with a unique counter diffusion of metal and linker solutions enabled unprecedented rapid synthesis of well-intergrown ZIF-7-8 membranes in ∼90 s, the fastest MOF membrane preparation up to date. Furthermore, we were able to tune the molecular sieving properties of the ZIF-7-8 membranes by varying the benzimidazole-to-2-methylimidazole (bIm-to-mIm) linker ratio in the hybrid frameworks. The tuning of their molecular sieving properties led to the systematic change in the permeance and selectivity of various small gases. The unprecedented rapid synthesis of well-intergrown ZIF-7-8 membranes with tunable molecular sieving properties is an important step forward for the commercial gas separation applications of ZIF membranes.

Synthesis of Selective Butyrylcholinesterase Inhibitors Coupled between α-Lipoic Acid and Polyphenols by Using 2-(Piperazin-1-yl)ethanol Linker

International Nuclear Information System (INIS)

Yeun, Go Heun; Lee, Seung Hwan; LIm, Yong Bae; Lee, Hye Sook; Lee, Bong Ho; Park, Jeong Ho; Won, Mooho

2013-01-01

In the previous paper (Bull. Korean Chem. Soc., 2011, 32, 2997), the hybrid molecules between α-lipoic acid (ALA) and polyphenols (PPs) connected with neutral 2-(2-aminoethoxy)ethanol linker (linker-1) showed new biological activity such as butyrylcholinesterase (BuChE) inhibition. In order to increase the binding affinity of the hybrid compounds to cholinesterase (ChE), the neutral 2-(2-aminoethoxy)ethanol (linker 1) was switched to the cationic 2-(piperazin-1-yl)ethanol linker (linker 2). The IC 50 values of the linker-2 hybrid molecules for BuChE inhibition were lower than those of linker-1 hybrid molecules (except 9-2) and they also had the same great selectivity for BuChE over AChE (> 800 fold) as linker-1 hybrid molecules. ALA-acetyl caffeic acid (10-2, ALA-AcCA) was shown as an effective inhibitor of BuChE (IC 50 = 0.44 ± 0.24 μM). A kinetic study using 7-2 showed that it is the same mixed type inhibition as 7-1. Its inhibition constant (Ki) to BuChE is 4.3 ± 0.09 μM

Synthesis of Selective Butyrylcholinesterase Inhibitors Coupled between α-Lipoic Acid and Polyphenols by Using 2-(Piperazin-1-yl)ethanol Linker

Energy Technology Data Exchange (ETDEWEB)

Yeun, Go Heun; Lee, Seung Hwan; LIm, Yong Bae; Lee, Hye Sook; Lee, Bong Ho; Park, Jeong Ho [Hanbat National Univ., Daejeon (Korea, Republic of); Won, Mooho [Kangwon National Univ., Chuncheon (Korea, Republic of)

2013-04-15

In the previous paper (Bull. Korean Chem. Soc., 2011, 32, 2997), the hybrid molecules between α-lipoic acid (ALA) and polyphenols (PPs) connected with neutral 2-(2-aminoethoxy)ethanol linker (linker-1) showed new biological activity such as butyrylcholinesterase (BuChE) inhibition. In order to increase the binding affinity of the hybrid compounds to cholinesterase (ChE), the neutral 2-(2-aminoethoxy)ethanol (linker 1) was switched to the cationic 2-(piperazin-1-yl)ethanol linker (linker 2). The IC{sub 50} values of the linker-2 hybrid molecules for BuChE inhibition were lower than those of linker-1 hybrid molecules (except 9-2) and they also had the same great selectivity for BuChE over AChE (> 800 fold) as linker-1 hybrid molecules. ALA-acetyl caffeic acid (10-2, ALA-AcCA) was shown as an effective inhibitor of BuChE (IC{sub 50} = 0.44 ± 0.24 μM). A kinetic study using 7-2 showed that it is the same mixed type inhibition as 7-1. Its inhibition constant (Ki) to BuChE is 4.3 ± 0.09 μM.

Unusual and highly tunable missing-linker defects in zirconium metal-organic framework UiO-66 and their important effects on gas adsorption.

Science.gov (United States)

Wu, Hui; Chua, Yong Shen; Krungleviciute, Vaiva; Tyagi, Madhusudan; Chen, Ping; Yildirim, Taner; Zhou, Wei

2013-07-17

UiO-66 is a highly important prototypical zirconium metal-organic framework (MOF) compound because of its excellent stabilities not typically found in common porous MOFs. In its perfect crystal structure, each Zr metal center is fully coordinated by 12 organic linkers to form a highly connected framework. Using high-resolution neutron power diffraction technique, we found the first direct structural evidence showing that real UiO-66 material contains significant amount of missing-linker defects, an unusual phenomenon for MOFs. The concentration of the missing-linker defects is surprisingly high, ∼10% in our sample, effectively reducing the framework connection from 12 to ∼11. We show that by varying the concentration of the acetic acid modulator and the synthesis time, the linker vacancies can be tuned systematically, leading to dramatically enhanced porosity. We obtained samples with pore volumes ranging from 0.44 to 1.0 cm(3)/g and Brunauer-Emmett-Teller surface areas ranging from 1000 to 1600 m(2)/g, the largest values of which are ∼150% and ∼60% higher than the theoretical values of defect-free UiO-66 crystal, respectively. The linker vacancies also have profound effects on the gas adsorption behaviors of UiO-66, in particular CO2. Finally, comparing the gas adsorption of hydroxylated and dehydroxylated UiO-66, we found that the former performs systematically better than the latter (particularly for CO2) suggesting the beneficial effect of the -OH groups. This finding is of great importance because hydroxylated UiO-66 is the practically more relevant, non-air-sensitive form of this MOF. The preferred gas adsorption on the metal center was confirmed by neutron diffraction measurements, and the gas binding strength enhancement by the -OH group was further supported by our first-principles calculations.

Regulation of Cellular Dynamics and Chromosomal Binding Site Preference of Linker Histones H1.0 and H1.X.

Science.gov (United States)

Okuwaki, Mitsuru; Abe, Mayumi; Hisaoka, Miharu; Nagata, Kyosuke

2016-11-01

Linker histones play important roles in the genomic organization of mammalian cells. Of the linker histone variants, H1.X shows the most dynamic behavior in the nucleus. Recent research has suggested that the linker histone variants H1.X and H1.0 have different chromosomal binding site preferences. However, it remains unclear how the dynamics and binding site preferences of linker histones are determined. Here, we biochemically demonstrated that the DNA/nucleosome and histone chaperone binding activities of H1.X are significantly lower than those of other linker histones. This explains why H1.X moves more rapidly than other linker histones in vivo Domain swapping between H1.0 and H1.X suggests that the globular domain (GD) and C-terminal domain (CTD) of H1.X independently contribute to the dynamic behavior of H1.X. Our results also suggest that the N-terminal domain (NTD), GD, and CTD cooperatively determine the preferential binding sites, and the contribution of each domain for this determination is different depending on the target genes. We also found that linker histones accumulate in the nucleoli when the nucleosome binding activities of the GDs are weak. Our results contribute to understanding the molecular mechanisms of dynamic behaviors, binding site selection, and localization of linker histones. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Bioinformatic Analysis Reveals Conservation of Intrinsic Disorder in the Linker Sequences of Prokaryotic Dual-family Immunophilin Chaperones.

Science.gov (United States)

Barik, Sailen

2018-01-01

The two classical immunophilin families, found essentially in all living cells, are: cyclophilin (CYN) and FK506-binding protein (FKBP). We previously reported a novel class of immunophilins that are natural chimera of these two, which we named dual-family immunophilin (DFI). The DFIs were found in either of two conformations: CYN-linker-FKBP (CFBP) or FKBP-3TPR-CYN (FCBP). While the 3TPR domain can serve as a flexible linker between the FKBP and CYN modules in the FCBP-type DFI, the linker sequences in the CFBP-type DFIs are relatively short, diverse in sequence, and contain no discernible motif or signature. Here, I present several lines of computational evidence that, regardless of their primary structure, these CFBP linkers are intrinsically disordered. This report provides the first molecular foundation for the model that the CFBP linker acts as an unstructured, flexible loop, allowing the two flanking chaperone modules function independently while linked in cis , likely to assist in the folding of multisubunit client complexes.

P-Link: A method for generating multicomponent cytochrome P450 fusions with variable linker length

DEFF Research Database (Denmark)

Belsare, Ketaki D.; Ruff, Anna Joelle; Martinez, Ronny

2014-01-01

Fusion protein construction is a widely employed biochemical technique, especially when it comes to multi-component enzymes such as cytochrome P450s. Here we describe a novel method for generating fusion proteins with variable linker lengths, protein fusion with variable linker insertion (P...

Prismatic substructure in metals; Prizmaticna substruktura kod metala

Energy Technology Data Exchange (ETDEWEB)

Milosavljevic, Dj [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Yugoslavia)

1965-11-15

The first step was the study of impurities behaviour during solidification of metals under equilibrium and non-equilibrium conditions. Impurities distribution and their structural shapes are dependent on conditions of solidification. These conditions are directly related to temperature and concentration issues on the solidification surface. Theoretical and experimental evaluated in this paper show the significance of subcooling in formation of cellular sub-structure.

Modulations of DNA Contacts by Linker Histones and Post-translational Modifications Determine the Mobility and Modifiability of Nucleosomal H3 Tails.

Science.gov (United States)

Stützer, Alexandra; Liokatis, Stamatios; Kiesel, Anja; Schwarzer, Dirk; Sprangers, Remco; Söding, Johannes; Selenko, Philipp; Fischle, Wolfgang

2016-01-21

Post-translational histone modifications and linker histone incorporation regulate chromatin structure and genome activity. How these systems interface on a molecular level is unclear. Using biochemistry and NMR spectroscopy, we deduced mechanistic insights into the modification behavior of N-terminal histone H3 tails in different nucleosomal contexts. We find that linker histones generally inhibit modifications of different H3 sites and reduce H3 tail dynamics in nucleosomes. These effects are caused by modulations of electrostatic interactions of H3 tails with linker DNA and largely depend on the C-terminal domains of linker histones. In agreement, linker histone occupancy and H3 tail modifications segregate on a genome-wide level. Charge-modulating modifications such as phosphorylation and acetylation weaken transient H3 tail-linker DNA interactions, increase H3 tail dynamics, and, concomitantly, enhance general modifiability. We propose that alterations of H3 tail-linker DNA interactions by linker histones and charge-modulating modifications execute basal control mechanisms of chromatin function. Copyright © 2016 Elsevier Inc. All rights reserved.

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

International Nuclear Information System (INIS)

Altheimer, A.; Thompson, E.N.; Arce, A.; Bjergaard, D.; Asquith, L.; Backus Mayes, J.; Hook, A.; Izaguirre, E.; Jankowiak, M.; Larkoski, A.; Nef, P.; Schwartzman, A.; Swiatlowski, M.; Wacker, J.; Kuutmann, E.B.; Berger, J.; Bryngemark, L.; Buckley, A.; Debenedetti, C.; Butterworth, J.; Campanelli, M.; Davison, A.; Cacciari, M.; Carli, T.; Roeck, A. de; Chala, M.; Chapleau, B.; Chen, C.; Chou, J.P.; Cornelissen, T.; Fleischmann, S.; Curtin, D.; Dasgupta, M.; Almeida Dias, F. de; De Cosa, A.; Doglioni, C.; Guescini, F.; Ellis, S.D.; Hornig, A.; Scholtz, J.; Fassi, F.; Hoz, S.G. de la; Kaci, M.; Oliver Garcia, E.; Rodrigo, G.; Salt, J.; Sanchez Martinez, V.; Villaplana, M.; Vos, M.; Ferrando, J.; Kar, D.; Nordstrom, K.; Freytsis, M.; Gonzalez Silva, M.L.; Han, Z.; Lopez Mateos, D.; Schwartz, M.D.; Juknevich, J.; Kasieczka, G.; Plehn, T.; Schaetzel, S.; Takeuchi, M.; Kogler, R.; Loch, P.; Marzani, S.; Spannowsky, M.; Masetti, L.; Mateu, V.; Stewart, I.; Thaler, J.; Miller, D.W.; Mishra, K.; Tran, N.V.; Penwell, J.; Pilot, J.; Rappoccio, S.; Rizzi, A.; Safonov, A.; Salam, G.P.; Schioppa, M.; Schmidt, A.; Segala, M.; Son, M.; Soyez, G.; Strom, D.; Vermilion, C.; Walsh, J.

2014-01-01

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. A final section summarizes the lessons learnt from jet substructure analyses in searches for new physics in the production of boosted top quarks. (orig.)

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

Energy Technology Data Exchange (ETDEWEB)

Altheimer, A.; Thompson, E.N. [Columbia University, Nevis Laboratory, Irvington, NY (United States); Arce, A.; Bjergaard, D. [Duke University, Durham, NC (United States); Asquith, L. [Argonne National Laboratory, Lemont, IL (United States); Backus Mayes, J.; Hook, A.; Izaguirre, E.; Jankowiak, M.; Larkoski, A.; Nef, P.; Schwartzman, A.; Swiatlowski, M.; Wacker, J. [SLAC National Accelerator Laboratory, Menlo Park, CA (United States); Kuutmann, E.B. [Deutsches Elektronen-Synchrotron, DESY, Zeuthen (Germany); Humboldt University, Berlin (Germany); Berger, J. [Cornell University, Ithaca, NY (United States); Bryngemark, L. [Lund University, Lund (Sweden); Buckley, A.; Debenedetti, C. [University of Edinburgh, Edinburgh (United Kingdom); Butterworth, J.; Campanelli, M.; Davison, A. [University College London, London (United Kingdom); Cacciari, M. [CERN, Geneva 23 (Switzerland); Carli, T.; Roeck, A. de [LPTHE, UPMC Univ. Paris 6 et CNRS UMR, Paris (France); Chala, M. [CAFPE and Univ. of Granada, Granada (Spain); Chapleau, B. [McGill University, Montreal, QC (Canada); Chen, C. [Iowa State University, Ames, IA (United States); Chou, J.P. [Rutgers University, Piscataway, NJ (United States); Cornelissen, T.; Fleischmann, S. [Bergische Universitaet Wuppertal, Wuppertal (Germany); Curtin, D. [YITP, Stony Brook University, Stony Brook, NY (United States); Dasgupta, M. [University of Manchester, Manchester (United Kingdom); Almeida Dias, F. de [UNESP-Universidade Estadual Paulista, Sao Paulo (Brazil); De Cosa, A. [INFN, Naples (Italy); University of Naples, Naples (Italy); Doglioni, C.; Guescini, F. [University of Geneva, Geneva 4 (Switzerland); Ellis, S.D.; Hornig, A.; Scholtz, J. [University of Washington, Seattle, WA (United States); Fassi, F.; Hoz, S.G. de la; Kaci, M.; Oliver Garcia, E.; Rodrigo, G.; Salt, J.; Sanchez Martinez, V.; Villaplana, M.; Vos, M. [Instituto de Fisica Corpuscular, IFIC/CSIC-UVEG, Valencia (Spain); Ferrando, J.; Kar, D.; Nordstrom, K. [University of Glasgow, Glasgow (United Kingdom); Freytsis, M. [University of California, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); University of California, Berkeley, CA (United States); Gonzalez Silva, M.L. [Universidad de Buenos Aires, Buenos Aires (Argentina); Han, Z.; Lopez Mateos, D.; Schwartz, M.D. [Harvard University, Cambridge, MA (United States); Juknevich, J. [Weizmann Institute, Rehovot (Israel); Kasieczka, G.; Plehn, T.; Schaetzel, S.; Takeuchi, M. [Universitaet Heidelberg, Heidelberg (Germany); Kogler, R. [Universitaet Hamburg, Hamburg (Germany); Loch, P. [University of Arizona, Tucson, AZ (United States); Marzani, S.; Spannowsky, M. [IPPP, University of Durham, Durham (United Kingdom); Masetti, L. [Universitaet Mainz, Mainz (Germany); Mateu, V.; Stewart, I.; Thaler, J. [MIT, Cambridge, MA (United States); Miller, D.W. [University of Chicago, Chicago, IL (United States); Mishra, K.; Tran, N.V. [Fermi National Accelerator Laboratory, Batavia, IL (United States); Penwell, J. [Indiana University, Bloomington, IN (United States); Pilot, J. [University of California, Davis, CA (United States); Rappoccio, S. [Johns Hopkins University, Baltimore, MD (United States); University at Buffalo, State University of New York, Buffalo, NY (United States); Rizzi, A. [INFN, Pisa (Italy); University of Pisa, Pisa (Italy); Safonov, A. [Texas A and M University, College Station, TX (United States); Salam, G.P. [CERN, Geneva 23 (Switzerland); LPTHE, UPMC Univ. Paris 6 et CNRS UMR, Paris (France); Schioppa, M. [INFN, Rende (IT); University of Calabria, Rende (IT); Schmidt, A. [Universitaet Hamburg, Hamburg (DE); Universitaet Heidelberg, Heidelberg (DE); Segala, M. [Brown University, Richmond, RI (US); Son, M. [Yale University, New Haven, CT (US); Soyez, G. [CEA Saclay, Gif-sur-Yvette (FR); Strom, D. [University of Illinois, Chicago, IL (US); Vermilion, C. [University of California, Lawrence Berkeley National Laboratory, Berkeley, CA (US); Walsh, J. [University of California, Berkeley, CA (US)

2014-03-15

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. A final section summarizes the lessons learnt from jet substructure analyses in searches for new physics in the production of boosted top quarks. (orig.)

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

KAUST Repository

Yu, Weili

2014-08-19

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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

KAUST Repository

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

2014-01-01

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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A substructure method to compute the 3D fluid-structure interaction during blowdown

International Nuclear Information System (INIS)

Guilbaud, D.; Axisa, F.; Gantenbein, F.; Gibert, R.J.

1983-08-01

The waves generated by a sudden rupture of a PWR primary pipe have an important mechanical effect on the internal structures of the vessel. This fluid-structure interaction has a strong 3D aspect. 3D finite element explicit methods can be applied. These methods take into account the non linearities of the problem but the calculation is heavy and expensive. We describe in this paper another type of method based on a substructure procedure: the vessel, internals and contained fluid are axisymmetrically described (AQUAMODE computer code). The pipes and contained fluid are monodimensionaly described (TEDEL-FLUIDE Computer Code). These substructures are characterized by their natural modes. Then, they are connected to another (connection of both structural and fluid nodes) the TRISTANA Computer Code. This method allows to compute correctly and cheaply the 3D fluid-structure effects. The treatment of certain non linearities is difficult because of the modal characterization of the substructures. However variations of contact conditions versus time can be introduced. We present here some validation tests and comparison with experimental results of the litterature

Effect of the SH3-SH2 domain linker sequence on the structure of Hck kinase.

Science.gov (United States)

Meiselbach, Heike; Sticht, Heinrich

2011-08-01

The coordination of activity in biological systems requires the existence of different signal transduction pathways that interact with one another and must be precisely regulated. The Src-family tyrosine kinases, which are found in many signaling pathways, differ in their physiological function despite their high overall structural similarity. In this context, the differences in the SH3-SH2 domain linkers might play a role for differential regulation, but the structural consequences of linker sequence remain poorly understood. We have therefore performed comparative molecular dynamics simulations of wildtype Hck and of a mutant Hck in which the SH3-SH2 domain linker is replaced by the corresponding sequence from the homologous kinase Lck. These simulations reveal that linker replacement not only affects the orientation of the SH3 domain itself, but also leads to an alternative conformation of the activation segment in the Hck kinase domain. The sequence of the SH3-SH2 domain linker thus exerts a remote effect on the active site geometry and might therefore play a role in modulating the structure of the inactive kinase or in fine-tuning the activation process itself.

First attempts towards the early detection of fatigued substructures using cyclic-loaded 20 MnMoNi 5 5 steel

International Nuclear Information System (INIS)

Dobmann, G.; Seibold, A.

1992-01-01

Materials subjected to cyclic loading undergo substructural changes which may affect service life. The low alloy, fine-grained structural steel 20 MnMoNi 5 5 is used to demonstrate how substructural changes detected using TEM techniques are a function of the number of cycles undergone. For a given cyclic loading the usage factor η=N/N f =0.5 can be derived. Initial investigations using nondestructive examination methods have indicated that substructural changes and magnetic variables can be correlated. (orig.)

RAG-3D: a search tool for RNA 3D substructures

Science.gov (United States)

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

2015-01-01

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. PMID:26304547

MS2Analyzer: A Software for Small Molecule Substructure Annotations from Accurate Tandem Mass Spectra

Science.gov (United States)

2015-01-01

Systematic analysis and interpretation of the large number of tandem mass spectra (MS/MS) obtained in metabolomics experiments is a bottleneck in discovery-driven research. MS/MS mass spectral libraries are small compared to all known small molecule structures and are often not freely available. MS2Analyzer was therefore developed to enable user-defined searches of thousands of spectra for mass spectral features such as neutral losses, m/z differences, and product and precursor ions from MS/MS spectra in MSP/MGF files. The software is freely available at http://fiehnlab.ucdavis.edu/projects/MS2Analyzer/. As the reference query set, 147 literature-reported neutral losses and their corresponding substructures were collected. This set was tested for accuracy of linking neutral loss analysis to substructure annotations using 19 329 accurate mass tandem mass spectra of structurally known compounds from the NIST11 MS/MS library. Validation studies showed that 92.1 ± 6.4% of 13 typical neutral losses such as acetylations, cysteine conjugates, or glycosylations are correct annotating the associated substructures, while the absence of mass spectra features does not necessarily imply the absence of such substructures. Use of this tool has been successfully demonstrated for complex lipids in microalgae. PMID:25263576

The unstructured linker arms of Mlh1-Pms1 are important for interactions with DNA during mismatch repair

Science.gov (United States)

Plys, Aaron J.; Rogacheva, Maria V.; Greene, Eric C.; Alani, Eric

2012-01-01

DNA mismatch repair (MMR) models have proposed that MSH proteins identify DNA polymerase errors while interacting with the DNA replication fork. MLH proteins (primarily Mlh1-Pms1 in baker’s yeast) then survey the genome for lesion-bound MSH proteins. The resulting MSH-MLH complex formed at a DNA lesion initiates downstream steps in repair. MLH proteins act as dimers and contain long (20 – 30 nanometers) unstructured arms that connect two terminal globular domains. These arms can vary between 100 to 300 amino acids in length, are highly divergent between organisms, and are resistant to amino acid substitutions. To test the roles of the linker arms in MMR, we engineered a protease cleavage site into the Mlh1 linker arm domain of baker’s yeast Mlh1-Pms1. Cleavage of the Mlh1 linker arm in vitro resulted in a defect in Mlh1-Pms1 DNA binding activity, and in vivo proteolytic cleavage resulted in a complete defect in MMR. We then generated a series of truncation mutants bearing Mlh1 and Pms1 linker arms of varying lengths. This work revealed that MMR is greatly compromised when portions of the Mlh1 linker are removed, whereas repair is less sensitive to truncation of the Pms1 linker arm. Purified complexes containing truncations in Mlh1 and Pms1 linker arms were analyzed and found to have differential defects in DNA binding that also correlated with the ability to form a ternary complex with Msh2-Msh6 and mismatch DNA. These observations are consistent with the unstructured linker domains of MLH proteins providing distinct interactions with DNA during MMR. PMID:22659005

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

Science.gov (United States)

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.

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

Energy Technology Data Exchange (ETDEWEB)

Logan, Stephen D. [United States Automotive Materials Partnership LLC, Southfield, MI (United States); Forsmark, Joy H. [United States Automotive Materials Partnership LLC, Southfield, MI (United States); Osborne, Richard [United States Automotive Materials Partnership LLC, Southfield, MI (United States)

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.

Face-based selection of corners in 3D substructuring

Czech Academy of Sciences Publication Activity Database

Šístek, Jakub; Čertíková, M.; Burda, P.; Novotný, J.

2012-01-01

Roč. 82, č. 10 (2012), s. 1799-1811 ISSN 0378-4754 R&D Projects: GA AV ČR IAA100760702 Institutional research plan: CEZ:AV0Z10190503 Keywords : domain decomposition * iterative substructuring * BDDC Subject RIV: BA - General Mathematics Impact factor: 0.836, year: 2012 http://www.sciencedirect.com/science/article/pii/S0378475411001820

SH2-catalytic domain linker heterogeneity influences allosteric coupling across the SFK family.

Science.gov (United States)

Register, A C; Leonard, Stephen E; Maly, Dustin J

2014-11-11

Src-family kinases (SFKs) make up a family of nine homologous multidomain tyrosine kinases whose misregulation is responsible for human disease (cancer, diabetes, inflammation, etc.). Despite overall sequence homology and identical domain architecture, differences in SH3 and SH2 regulatory domain accessibility and ability to allosterically autoinhibit the ATP-binding site have been observed for the prototypical SFKs Src and Hck. Biochemical and structural studies indicate that the SH2-catalytic domain (SH2-CD) linker, the intramolecular binding epitope for SFK SH3 domains, is responsible for allosterically coupling SH3 domain engagement to autoinhibition of the ATP-binding site through the conformation of the αC helix. As a relatively unconserved region between SFK family members, SH2-CD linker sequence variability across the SFK family is likely a source of nonredundant cellular functions between individual SFKs via its effect on the availability of SH3 and SH2 domains for intermolecular interactions and post-translational modification. Using a combination of SFKs engineered with enhanced or weakened regulatory domain intramolecular interactions and conformation-selective inhibitors that report αC helix conformation, this study explores how SH2-CD sequence heterogeneity affects allosteric coupling across the SFK family by examining Lyn, Fyn1, and Fyn2. Analyses of Fyn1 and Fyn2, isoforms that are identical but for a 50-residue sequence spanning the SH2-CD linker, demonstrate that SH2-CD linker sequence differences can have profound effects on allosteric coupling between otherwise identical kinases. Most notably, a dampened allosteric connection between the SH3 domain and αC helix leads to greater autoinhibitory phosphorylation by Csk, illustrating the complex effects of SH2-CD linker sequence on cellular function.

A photolabile linker for the solid-phase synthesis of 4-substituted NH-1,2,3-triazoles

DEFF Research Database (Denmark)

Qvortrup, Katrine; Nielsen, Thomas Eiland

2011-01-01

A novel photolabile linker for solid-phase synthesis is presented. The linker displays an azido handle for copper-catalyzed azide–alkyne cycloaddition reactions with a variety of alkynes, remains intact under typical solid-phase reaction conditions, and enables a mild photolytic release of 4...

DETECTION OF LENSING SUBSTRUCTURE USING ALMA OBSERVATIONS OF THE DUSTY GALAXY SDP.81

Energy Technology Data Exchange (ETDEWEB)

Hezaveh, Yashar D.; Mao, Yao-Yuan; Morningstar, Warren; Blandford, Roger D.; Levasseur, Laurence Perreault; Wechsler, Risa H. [Kavli Institute for Particle Astrophysics and Cosmology and Department of Physics, Stanford University, 452 Lomita Mall, Stanford, CA 94305-4085 (United States); Dalal, Neal; Wen, Di; Kemball, Athol; Vieira, Joaquin D. [Astronomy Department, University of Illinois at Urbana-Champaign, 1002 W. Green Street, Urbana IL 61801 (United States); Marrone, Daniel P. [Steward Observatory, University of Arizona, 933 North Cherry Avenue, Tucson, AZ 85721 (United States); Carlstrom, John E. [Kavli Institute for Cosmological Physics, University of Chicago, 5640 South Ellis Avenue, Chicago, IL 60637 (United States); Fassnacht, Christopher D. [Department of Physics, University of California, One Shields Avenue, Davis, CA 95616 (United States); Holder, Gilbert P. [Department of Physics, McGill University, 3600 Rue University, Montreal, Quebec H3A 2T8 (Canada); Marshall, Philip J. [Kavli Institute for Particle Astrophysics and Cosmology and Department of Particle Physics and Astrophysics, SLAC National Accelerator Laboratory, Menlo Park, CA 94305 (United States); Murray, Norman [CITA, University of Toronto, 60 St. George St., Toronto ON M5S 3H8 (Canada)

2016-05-20

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 = 10{sup 8.96±0.12} M {sub ⊙} subhalo near one of the images, with a significance of 6.9 σ 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 × 10{sup 7} M {sub ⊙}, 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. Observations of larger samples of gravitational lenses with ALMA should be able to improve the constraints on the abundance of galactic substructure.

DETECTION OF LENSING SUBSTRUCTURE USING ALMA OBSERVATIONS OF THE DUSTY GALAXY SDP.81

International Nuclear Information System (INIS)

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

2016-01-01

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 = 10 8.96±0.12 M ⊙ subhalo near one of the images, with a significance of 6.9 σ 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 × 10 7 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. Observations of larger samples of gravitational lenses with ALMA should be able to improve the constraints on the abundance of galactic substructure.

cis-Apa: a practical linker for the microwave-assisted preparation of cyclic pseudopeptides via RCM cyclative cleavage.

Science.gov (United States)

Baron, Alice; Verdié, Pascal; Martinez, Jean; Lamaty, Frédéric

2011-02-04

A new linker cis-5-aminopent-3-enoic acid (cis-Apa) was prepared for the synthesis of cyclic pseudopeptides by cyclization-cleavage by using ring-closing methatesis (RCM). We developed a new synthetic pathway for the preparation of the cis-Apa linker that was tested in the cyclization-cleavage process of different RGD peptide sequences. Different macrocyclic peptidomimetics were prepared by using this integrated microwave-assisted method, showing that the readily available cis-Apa amino acid is well adapted as a linker in the cyclization-cleavage process.

Design and Analysis of Jacket Substructures for Offshore Wind Turbines

Directory of Open Access Journals (Sweden)

I-Wen Chen

2016-04-01

Full Text Available This study focused on investigating various existing types of offshore jacket substructures along with a proposed twisted-tripod jacket type (modified jacket (MJ-structures. The architectures of the three-leg structure, as well as the patented twisted jacket structure motivated the design of the proposed MJ-structures. The dimensions of the structures were designed iteratively using static stress analysis to ensure that all structures had a similar level of load-carrying capability. The numerical global buckling analyses were performed for all structures after the validation by the scaled-down experiments. The local buckling strength of all compressive members was analyzed using the NORSOK standard. The results showed that the proposed MJ-structures possess excellent structural behavior and few structural nodes and components competitive with the patented twisted jacket structures, while still maintaining the advantages of low material usage similar to the three-leg jacket structures. This study provides alternatives for the initial selection and design of offshore wind turbine substructures for green energy applications.

A Novel MS-Cleavable Azo Cross-Linker for Peptide Structure Analysis by Free Radical Initiated Peptide Sequencing (FRIPS)

Science.gov (United States)

Iacobucci, Claudio; Hage, Christoph; Schäfer, Mathias; Sinz, Andrea

2017-10-01

The chemical cross-linking/mass spectrometry (MS) approach is a growing research field in structural proteomics that allows gaining insights into protein conformations. It relies on creating distance constraints between cross-linked amino acid side chains that can further be used to derive protein structures. Currently, the most urgent task for designing novel cross-linking principles is an unambiguous and automated assignment of the created cross-linked products. Here, we introduce the homobifunctional, amine-reactive, and water soluble cross-linker azobisimidoester (ABI) as a prototype of a novel class of cross-linkers. The ABI-linker possesses an innovative modular scaffold combining the benefits of collisional activation lability with open shell chemistry. This MS-cleavable cross-linker can be efficiently operated via free radical initiated peptide sequencing (FRIPS) in positive ionization mode. Our proof-of-principle study challenges the gas phase behavior of the ABI-linker for the three amino acids, lysine, leucine, and isoleucine, as well as the model peptide thymopentin. The isomeric amino acids leucine and isoleucine could be discriminated by their characteristic side chain fragments. Collisional activation experiments were conducted via positive electrospray ionization (ESI) on two Orbitrap mass spectrometers. The ABI-mediated formation of odd electron product ions in MS/MS and MS3 experiments was evaluated and compared with a previously described azo-based cross-linker. All cross-linked products were amenable to automated analysis by the MeroX software, underlining the future potential of the ABI-linker for structural proteomics studies. [Figure not available: see fulltext.

Charged residues in the H-NS linker drive DNA binding and gene silencing in single cells.

Science.gov (United States)

Gao, Yunfeng; Foo, Yong Hwee; Winardhi, Ricksen S; Tang, Qingnan; Yan, Jie; Kenney, Linda J

2017-11-21

Nucleoid-associated proteins (NAPs) facilitate chromosome organization in bacteria, but the precise mechanism remains elusive. H-NS is a NAP that also plays a major role in silencing pathogen genes. We used genetics, single-particle tracking in live cells, superresolution microscopy, atomic force microscopy, and molecular dynamics simulations to examine H-NS/DNA interactions in single cells. We discovered a role for the unstructured linker region connecting the N-terminal oligomerization and C-terminal DNA binding domains. In the present work we demonstrate that linker amino acids promote engagement with DNA. In the absence of linker contacts, H-NS binding is significantly reduced, although no change in chromosome compaction is observed. H-NS is not localized to two distinct foci; rather, it is scattered all around the nucleoid. The linker makes DNA contacts that are required for gene silencing, while chromosome compaction does not appear to be an important H-NS function.

How to remain nonfolded and pliable: the linkers in modular α-amylases as a case study.

Science.gov (United States)

Feller, Georges; Dehareng, Dominique; Lage, Jean-Luc Da

2011-07-01

The primary structure of linkers in a new class of modular α-amylases constitutes a paradigm of the structural basis that allows a polypeptide to remain nonfolded, extended and pliable. Unfolding is mediated through a depletion of hydrophobic residues and an enrichment of hydrophilic residues, amongst which Ser and Thr are over-represented. An extended and flexible conformation is promoted by the sequential arrangement of Pro and Gly, which are the most abundant residues in these linkers. This is complemented by charge repulsion, charge clustering and disulfide-bridged loops. Molecular dynamics simulations suggest the existence of conformational transitions resulting from a transient and localized hydrophobic collapse, arising from the peculiar composition of the linkers. Accordingly, these linkers should not be regarded as fully disordered, but rather as possessing various discrete structural patterns allowing them to fulfill their biological function as a free energy reservoir for concerted motions between structured domains. © 2011 The Authors Journal compilation © 2011 FEBS.

Universal parametrization for quark and lepton substructure

International Nuclear Information System (INIS)

Akama, Keiichi; Terazawa, Hidezumi.

1994-01-01

A universal parametrization for possible quark and lepton substructure is advocated in terms of quark and lepton form factors. It is emphasized that the lower bounds on compositeness scale, Λ c , to be determined experimentally strongly depend on their definitions in composite models. From the recent HERA data, it is estimated to be Λ c > 50 GeV, 0.4 TeV and 10 TeV, depending on the parametrizations with a single-pole form factor, a contact interaction and a logarithmic form factor, respectively. (author)

Jacket Substructure Fatigue Mitigation through Active Control

DEFF Research Database (Denmark)

Hanis, Tomas; Natarajan, Anand

2014-01-01

to the fatigue design loads on the braces of the jacket. Since large wind turbines of 10MW rating have low rotor speeds (p), the modal frequencies of the sub structures approach 3p at low wind speeds, which leads to a modal coupling and resonance. Therefore an active control system is developed which provides...... sufficient structural damping and consequently a fatigue reduction at the substructure. The resulting reduction in fatigue design loads on the jacket structure based on the active control system is presented....

Molecular dissection of the interaction between the SH3 domain and the SH2-Kinase Linker region in PTK6.

Science.gov (United States)

Kim, Han Ie; Jung, Jinwon; Lee, Eun-Saem; Kim, Yong-Chul; Lee, Weontae; Lee, Seung-Taek

2007-11-03

PTK6 (also known as Brk) is an intracellular tyrosine kinase that contains SH3, SH2, and tyrosine kinase catalytic (Kinase) domains. The SH3 domain of PTK6 interacts with the N-terminal half of the linker (Linker) region between the SH2 and Kinase domains. Site-directed mutagenesis and surface plasmon resonance studies showed that a tryptophan residue (Trp44) in the SH3 domain and proline residues in the Linker region, in the order of Pro177, Pro175, and Pro179, contribute to the interaction. The three-dimensional modeled structure of the SH3-Linker complex was in agreement with the biochemical data. Disruption of the intramolecular interaction between the SH3 domain and the Linker region by mutation of Trp44, Pro175, Pro177, and Pro179 markedly increased the catalytic activity of PTK6 in HEK 293 cells. These results demonstrate that Trp44 in the SH3 domain and Pro177, Pro175, and Pro179 in the N-terminal half of the Linker region play important roles in the SH3-Linker interaction to maintain the protein in an inactive conformation along with the phosphorylated Tyr447-SH2 interaction.

Indirect Inverse Substructuring Method for Multibody Product Transport System with Rigid and Flexible Coupling

Directory of Open Access Journals (Sweden)

Jun Wang

2015-01-01

Full Text Available The aim of this paper is to develop a new frequency response function- (FRF- based indirect inverse substructuring method without measuring system-level FRFs in the coupling DOFs for the analysis of the dynamic characteristics of a three-substructure coupled product transport system with rigid and flexible coupling. By enforcing the dynamic equilibrium conditions at the coupling coordinates and the displacement compatibility conditions, a closed-form analytical solution to inverse substructuring analysis of multisubstructure coupled product transport system is derived based on the relationship of easy-to-monitor component-level FRFs and the system-level FRFs at the coupling coordinates. The proposed method is validated by a lumped mass-spring-damper model, and the predicted coupling dynamic stiffness is compared with the direct computation, showing exact agreement. The method developed offers an approach to predict the unknown coupling dynamic stiffness from measured FRFs purely. The suggested method may help to obtain the main controlling factors and contributions from the various structure-borne paths for product transport system.

Fivefold increase of hydrogen uptake in MOF74 through linker decorations

Science.gov (United States)

Arter, C. A.; Zuluaga, S.; Harrison, D.; Welchman, E.; Thonhauser, T.

2016-10-01

We present ab initio results for linker decorations in Mg-MOF74, i.e., attaching various metals M =Li, Na, K, Sc, Cr, Mn, Fe, Ni, Cu, Zn, Rb, Pd, Ag, and Pt near the ring of the linker, creating new strong adsorption sites and thus maximizing small-molecule uptake. We find that in most cases these decorations influence the overall form and structure of Mg-MOF74 only marginally. After the initial screening, we chose metals that bind favorably to the linker and further investigated adsorption of H2,CO2, and H2O for M =Li , Na, K, and Sc. For the case of H2 we show that up to 24 additional guest molecules can be adsorbed in the metal-organic framework (MOF) unit cell, with binding energies comparable to the original open-metal sites at the six corners of the channel. This leads to a fivefold increase of the molecule uptake in Mg-MOF74, with tremendous impact on many applications in general and hydrogen storage in particular, where the gravimetric hydrogen density increases from 1.63 to 7.28 mass % and the volumetric density increases from 15.10 to 75.50 g H2L-1 .

X-ray and optical substructures of the DAFT/FADA survey clusters

Science.gov (United States)

Guennou, L.; Durret, F.; Adami, C.; Lima Neto, G. B.

2013-04-01

We have undertaken the DAFT/FADA survey with the double aim of setting constraints on dark energy based on weak lensing tomography and of obtaining homogeneous and high quality data for a sample of 91 massive clusters in the redshift range 0.4-0.9 for which there were HST archive data. We have analysed the XMM-Newton data available for 42 of these clusters to derive their X-ray temperatures and luminosities and search for substructures. Out of these, a spatial analysis was possible for 30 clusters, but only 23 had deep enough X-ray data for a really robust analysis. This study was coupled with a dynamical analysis for the 26 clusters having at least 30 spectroscopic galaxy redshifts in the cluster range. Altogether, the X-ray sample of 23 clusters and the optical sample of 26 clusters have 14 clusters in common. We present preliminary results on the coupled X-ray and dynamical analyses of these 14 clusters.

[Construction of cTnC-linker-TnI (P) Genes, Expression of Fusion Protein and Preparation of Lyophilized Protein].

Science.gov (United States)

Song, Xiaoli; Liu, Xiaoyun; Cai, Lei; Wu, Jianwei; Wang, Jihua

2015-12-01

In order to construct and express human cardiac troponin C-linker-troponin I(P) [ cTnC-linker-TnI(P)] fusion protein, detect its activity and prepare lyophilized protein, we searched the CDs of human cTnC and cTnI from GenBank, synthesized cTnC and cTnI(30-110aa) into cloning vector by a short DNA sequence coding for 15 neutral amino acid residues. pCold I-cTnC-linker-TnI(P) was constructed and transformed into E. coli BL21(DE3). Then, cTnC-linker-TnI(P) fusion protein was induced by isopropyl-β-D-thiogalactopyranoside (IPTG). Soluable expression of cTnC-linker-TnI(P) in prokaryotic system was successfully obtained. The fusion protein was purified by Ni²⁺ Sepharose 6 Fast Flow affinity chromatography with over 95% purity and prepared into lyophilized protein. The activity of purified cTnC-linker-TnI(P) and its lyophilized protein were detected by Wondfo Finecare™ cTnI Test. Lyophilized protein of cTnC-linker-TnI(P) was stable for 10 or more days at 37 °C and 4 or more months at 25 °C and 4 °C. The expression system established in this research is feasible and efficient. Lyophilized protein is stable enough to be provided as biological raw materials for further research.

Observation of lateral substructures in EAS by measurement of the time distribution of atmospheric Cerenkov light

International Nuclear Information System (INIS)

Bosia, G.; Navarra, G.; Saavedra, O.

1975-01-01

The lateral structure of EAS is derived from the arrival time distribution of atmospheric Cerenkov light assuming a strict correlation between time structure and lateral particle distribution. Results of the Pic du Midi experiment are presented. Substructures in the time distribution of the Cerenkov light can be related to structures in the lateral density distribution of electrons. The frequency (a few %) of substructures can be explained within conventional models of high energy interactions. (orig.) [de

Effective generation of transgenic pigs and mice by linker based sperm-mediated gene transfer.

OpenAIRE

Chang, Keejong; Qian, Jin; Jiang, MeiSheng; Liu, Yi-Hsin; Wu, Ming-Che; Chen, Chi-Dar; Lai, Chao-Kuen; Lo, Hsin-Lung; Hsiao, Chin-Ton; Brown, Lucy; Bolen, James; Huang, Hsiao-I; Ho, Pei-Yu; Shih, Ping Yao; Yao, Chen-Wen

2002-01-01

Abstract Background Transgenic animals have become valuable tools for both research and applied purposes. The current method of gene transfer, microinjection, which is widely used in transgenic mouse production, has only had limited success in producing transgenic animals of larger or higher species. Here, we report a linker based sperm-mediated gene transfer method (LB-SMGT) that greatly improves the production efficiency of large transgenic animals. Results The linker protein, a monoclonal ...

ATPase Domain and Interdomain Linker Play a Key Role in Aggregation of Mitochondrial Hsp70 Chaperone Ssc1*

Science.gov (United States)

Blamowska, Marta; Sichting, Martin; Mapa, Koyeli; Mokranjac, Dejana; Neupert, Walter; Hell, Kai

2010-01-01

The co-chaperone Hep1 is required to prevent the aggregation of mitochondrial Hsp70 proteins. We have analyzed the interaction of Hep1 with mitochondrial Hsp70 (Ssc1) and the determinants in Ssc1 that make it prone to aggregation. The ATPase and peptide binding domain (PBD) of Hsp70 proteins are connected by a linker segment that mediates interdomain communication between the domains. We show here that the minimal Hep1 binding entity of Ssc1 consists of the ATPase domain and the interdomain linker. In the absence of Hep1, the ATPase domain with the interdomain linker had the tendency to aggregate, in contrast to the ATPase domain with the mutated linker segment or without linker, and in contrast to the PBD. The closest homolog of Ssc1, bacterial DnaK, and a Ssc1 chimera, in which a segment of the ATPase domain of Ssc1 was replaced by the corresponding segment from DnaK, did not aggregate in Δhep1 mitochondria. The propensity to aggregate appears to be a specific property of the mitochondrial Hsp70 proteins. The ATPase domain in combination with the interdomain linker is crucial for aggregation of Ssc1. In conclusion, our results suggest that interdomain communication makes Ssc1 prone to aggregation. Hep1 counteracts aggregation by binding to this aggregation-prone conformer. PMID:20007714

ATPase domain and interdomain linker play a key role in aggregation of mitochondrial Hsp70 chaperone Ssc1.

Science.gov (United States)

Blamowska, Marta; Sichting, Martin; Mapa, Koyeli; Mokranjac, Dejana; Neupert, Walter; Hell, Kai

2010-02-12

The co-chaperone Hep1 is required to prevent the aggregation of mitochondrial Hsp70 proteins. We have analyzed the interaction of Hep1 with mitochondrial Hsp70 (Ssc1) and the determinants in Ssc1 that make it prone to aggregation. The ATPase and peptide binding domain (PBD) of Hsp70 proteins are connected by a linker segment that mediates interdomain communication between the domains. We show here that the minimal Hep1 binding entity of Ssc1 consists of the ATPase domain and the interdomain linker. In the absence of Hep1, the ATPase domain with the interdomain linker had the tendency to aggregate, in contrast to the ATPase domain with the mutated linker segment or without linker, and in contrast to the PBD. The closest homolog of Ssc1, bacterial DnaK, and a Ssc1 chimera, in which a segment of the ATPase domain of Ssc1 was replaced by the corresponding segment from DnaK, did not aggregate in Delta hep1 mitochondria. The propensity to aggregate appears to be a specific property of the mitochondrial Hsp70 proteins. The ATPase domain in combination with the interdomain linker is crucial for aggregation of Ssc1. In conclusion, our results suggest that interdomain communication makes Ssc1 prone to aggregation. Hep1 counteracts aggregation by binding to this aggregation-prone conformer.

Substructure boosts to dark matter annihilation from Sommerfeld enhancement

International Nuclear Information System (INIS)

Bovy, Jo

2009-01-01

The recently introduced Sommerfeld enhancement of the dark matter annihilation cross section has important implications for the detection of dark matter annihilation in subhalos in the Galactic halo. In addition to the boost to the dark matter annihilation cross section from the high densities of these subhalos with respect to the main halo, an additional boost caused by the Sommerfeld enhancement results from the fact that they are kinematically colder than the Galactic halo. If we further believe the generic prediction of the cold dark matter paradigm that in each subhalo there is an abundance of substructure which is approximately self-similar to that of the Galactic halo, then I show that additional boosts coming from the density enhancements of these small substructures and their small velocity dispersions enhance the dark matter annihilation cross section even further. I find that very large boost factors (10 5 to 10 9 ) are obtained in a large class of models. The implications of these boost factors for the detection of dark matter annihilation from dwarf spheroidal galaxies in the Galactic halo are such that, generically, they outshine the background gamma-ray flux and are detectable by the Fermi Gamma-ray Space Telescope.

Factorization for groomed jet substructure beyond the next-to-leading logarithm

Energy Technology Data Exchange (ETDEWEB)

Frye, Christopher; Larkoski, Andrew J.; Schwartz, Matthew D.; Yan, Kai [Center for the Fundamental Laws of Nature, Harvard University,17 Oxford Street, Cambridge, MA 02138 (United States)

2016-07-12

Jet grooming algorithms are widely used in experimental analyses at hadron colliders to remove contaminating radiation from within jets. While the algorithms perform a great service to the experiments, their intricate algorithmic structure and multiple parameters has frustrated precision theoretic understanding. In this paper, we demonstrate that one particular groomer called soft drop actually makes precision jet substructure easier. In particular, we derive a factorization formula for a large class of soft drop jet substructure observables, including jet mass. The essential observation that allows for this factorization is that, without the soft wide-angle radiation groomed by soft drop, all singular contributions are collinear. The simplicity and universality of the collinear limit in QCD allows us to show that to all orders, the normalized differential cross section has no contributions from non-global logarithms. It is also independent of process, up to the relative fraction of quark and gluon jets. In fact, soft drop allows us to define this fraction precisely. The factorization theorem also explains why soft drop observables are less sensitive to hadronization than their ungroomed counterparts. Using the factorization theorem, we resum the soft drop jet mass to next-to-next-to-leading logarithmic accuracy. This requires calculating some clustering effects that are closely related to corresponding effects found in jet veto calculations. We match our resummed calculation to fixed order results for both e{sup +}e{sup −}→ dijets and pp→Z+j events, producing the first jet substructure predictions (groomed or ungroomed) to this accuracy for the LHC.

Factorization for groomed jet substructure beyond the next-to-leading logarithm

International Nuclear Information System (INIS)

Frye, Christopher; Larkoski, Andrew J.; Schwartz, Matthew D.; Yan, Kai

2016-01-01

Jet grooming algorithms are widely used in experimental analyses at hadron colliders to remove contaminating radiation from within jets. While the algorithms perform a great service to the experiments, their intricate algorithmic structure and multiple parameters has frustrated precision theoretic understanding. In this paper, we demonstrate that one particular groomer called soft drop actually makes precision jet substructure easier. In particular, we derive a factorization formula for a large class of soft drop jet substructure observables, including jet mass. The essential observation that allows for this factorization is that, without the soft wide-angle radiation groomed by soft drop, all singular contributions are collinear. The simplicity and universality of the collinear limit in QCD allows us to show that to all orders, the normalized differential cross section has no contributions from non-global logarithms. It is also independent of process, up to the relative fraction of quark and gluon jets. In fact, soft drop allows us to define this fraction precisely. The factorization theorem also explains why soft drop observables are less sensitive to hadronization than their ungroomed counterparts. Using the factorization theorem, we resum the soft drop jet mass to next-to-next-to-leading logarithmic accuracy. This requires calculating some clustering effects that are closely related to corresponding effects found in jet veto calculations. We match our resummed calculation to fixed order results for both e + e − → dijets and pp→Z+j events, producing the first jet substructure predictions (groomed or ungroomed) to this accuracy for the LHC.

Novel mixing method for cross linker introduction into droplet emulsions

CSIR Research Space (South Africa)

Land, KJ

2013-10-01

Full Text Available the introduction of cross linker after droplet formation, together with the utilisation of topological microfluidic channel structures, allowing for the novel manufacture of particles. Flow over these structures has been simulated in order to choose the most...

One-pot preparation of mRNA/cDNA display by a novel and versatile puromycin-linker DNA.

Science.gov (United States)

Mochizuki, Yuki; Biyani, Manish; Tsuji-Ueno, Sachika; Suzuki, Miho; Nishigaki, Koichi; Husimi, Yuzuru; Nemoto, Naoto

2011-09-12

A rapid, easy, and robust preparation method for mRNA/cDNA display using a newly designed puromycin-linker DNA is presented. The new linker is structurally simple, easy to synthesize, and cost-effective for use in "in vitro peptide and protein selection". An introduction of RNase T1 nuclease site to the new linker facilitates the easy recovery of mRNA/cDNA displayed protein by an improvement of the efficiency of ligating the linker to mRNAs and efficient release of mRNA/cDNA displayed protein from the solid-phase (magnetic bead). For application demonstration, affinity selections were successfully performed. Furthermore, we introduced a "one-pot" preparation protocol to perform mRNA display easy. Unlike conventional approaches that require tedious and downstream multistep process including purification, this protocol will make the mRNA/cDNA display methods more practical and convenient and also facilitate the development of next-generation, high-throughput mRNA/cDNA display systems amenable to automation.

Halo substructure in the SDSS-Gaia catalogue: streams and clumps

Science.gov (United States)

Myeong, G. C.; Evans, N. W.; Belokurov, V.; Amorisco, N. C.; Koposov, S. E.

2018-04-01

We use the Sloan Digital Sky Survey (SDSS)-Gaia Catalogue to identify six new pieces of halo substructure. SDSS-Gaia is an astrometric catalogue that exploits SDSS data release 9 to provide first epoch photometry for objects in the Gaia source catalogue. We use a version of the catalogue containing 245 316 stars with all phase-space coordinates within a heliocentric distance of ˜10 kpc. We devise a method to assess the significance of halo substructures based on their clustering in velocity space. The two most substantial structures are multiple wraps of a stream which has undergone considerable phase mixing (S1, with 94 members) and a kinematically cold stream (S2, with 61 members). The member stars of S1 have a median position of (X, Y, Z) = (8.12, -0.22, 2.75) kpc and a median metallicity of [Fe/H] = -1.78. The stars of S2 have median coordinates (X, Y, Z) = (8.66, 0.30, 0.77) kpc and a median metallicity of [Fe/H] = -1.91. They lie in velocity space close to some of the stars in the stream reported by Helmi et al. By modelling, we estimate that both structures had progenitors with virial masses ≈1010M⊙ and infall times ≳ 9 Gyr ago. Using abundance matching, these correspond to stellar masses between 106 and 107M⊙. These are somewhat larger than the masses inferred through the mass-metallicity relation by factors of 5 to 15. Additionally, we identify two further substructures (S3 and S4 with 55 and 40 members) and two clusters or moving group (C1 and C2 with 24 and 12) members. In all six cases, clustering in kinematics is found to correspond to clustering in both configuration space and metallicity, adding credence to the reliability of our detections.

Accurate distance determination of nucleic acids via Förster resonance energy transfer: implications of dye linker length and rigidity.

Science.gov (United States)

Sindbert, Simon; Kalinin, Stanislav; Nguyen, Hien; Kienzler, Andrea; Clima, Lilia; Bannwarth, Willi; Appel, Bettina; Müller, Sabine; Seidel, Claus A M

2011-03-02

In Förster resonance energy transfer (FRET) experiments, the donor (D) and acceptor (A) fluorophores are usually attached to the macromolecule of interest via long flexible linkers of up to 15 Å in length. This causes significant uncertainties in quantitative distance measurements and prevents experiments with short distances between the attachment points of the dyes due to possible dye-dye interactions. We present two approaches to overcome the above problems as demonstrated by FRET measurements for a series of dsDNA and dsRNA internally labeled with Alexa488 and Cy5 as D and A dye, respectively. First, we characterize the influence of linker length and flexibility on FRET for different dye linker types (long, intermediate, short) by analyzing fluorescence lifetime and anisotropy decays. For long linkers, we describe a straightforward procedure that allows for very high accuracy of FRET-based structure determination through proper consideration of the position distribution of the dye and of linker dynamics. The position distribution can be quickly calculated with geometric accessible volume (AV) simulations, provided that the local structure of RNA or DNA in the proximity of the dye is known and that the dye diffuses freely in the sterically allowed space. The AV approach provides results similar to molecular dynamics simulations (MD) and is fully consistent with experimental FRET data. In a benchmark study for ds A-RNA, an rmsd value of 1.3 Å is achieved. Considering the case of undefined dye environments or very short DA distances, we introduce short linkers with a propargyl or alkenyl unit for internal labeling of nucleic acids to minimize position uncertainties. Studies by ensemble time correlated single photon counting and single-molecule detection show that the nature of the linker strongly affects the radius of the dye's accessible volume (6-16 Å). For short propargyl linkers, heterogeneous dye environments are observed on the millisecond time scale. A

Pivotal role of extended linker 2 in the activation of Gα by G protein-coupled receptor.

Science.gov (United States)

Huang, Jianyun; Sun, Yutong; Zhang, J Jillian; Huang, Xin-Yun

2015-01-02

G protein-coupled receptors (GPCRs) relay extracellular signals mainly to heterotrimeric G-proteins (Gαβγ) and they are the most successful drug targets. The mechanisms of G-protein activation by GPCRs are not well understood. Previous studies have revealed a signal relay route from a GPCR via the C-terminal α5-helix of Gα to the guanine nucleotide-binding pocket. Recent structural and biophysical studies uncover a role for the opening or rotating of the α-helical domain of Gα during the activation of Gα by a GPCR. Here we show that β-adrenergic receptors activate eight Gαs mutant proteins (from a screen of 66 Gαs mutants) that are unable to bind Gβγ subunits in cells. Five of these eight mutants are in the αF/Linker 2/β2 hinge region (extended Linker 2) that connects the Ras-like GTPase domain and the α-helical domain of Gαs. This extended Linker 2 is the target site of a natural product inhibitor of Gq. Our data show that the extended Linker 2 is critical for Gα activation by GPCRs. We propose that a GPCR via its intracellular loop 2 directly interacts with the β2/β3 loop of Gα to communicate to Linker 2, resulting in the opening and closing of the α-helical domain and the release of GDP during G-protein activation. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Solid-phase synthesis of polyfunctional polylysine dendrons using aldehyde linkers

DEFF Research Database (Denmark)

Svenssen, Daniel K.; Mirsharghi, Sahar; Boas, Ulrik

2014-01-01

A straightforward method for the solid-phase synthesis of C-terminally modified polylysine dendrons has been developed by applying bisalkoxybenzaldehyde and trisalkoxybenzaldehyde linkers. The method has been used for the synthesis of polylysine dendrons with a variety of C-terminal ‘tail groups’...

Modification of Titanium Substrates with Chimeric Peptides Comprising Antimicrobial and Titanium-Binding Motifs Connected by Linkers To Inhibit Biofilm Formation.

Science.gov (United States)

Liu, Zihao; Ma, Shiqing; Duan, Shun; Xuliang, Deng; Sun, Yingchun; Zhang, Xi; Xu, Xinhua; Guan, Binbin; Wang, Chao; Hu, Meilin; Qi, Xingying; Zhang, Xu; Gao, Ping

2016-03-02

Bacterial adhesion and biofilm formation are the primary causes of implant-associated infection, which is difficult to eliminate and may induce failure in dental implants. Chimeric peptides with both binding and antimicrobial motifs may provide a promising alternative to inhibit biofilm formation on titanium surfaces. In this study, chimeric peptides were designed by connecting an antimicrobial motif (JH8194: KRLFRRWQWRMKKY) with a binding motif (minTBP-1: RKLPDA) directly or via flexible/rigid linkers to modify Ti surfaces. We evaluated the binding behavior of peptides using quartz crystal microbalance (QCM) and atomic force microscopy (AFM) techniques and investigated the effect of the modification of titanium surfaces with these peptides on the bioactivity of Streptococcus gordonii (S. gordonii) and Streptococcus sanguis (S. sanguis). Compared with the flexible linker (GGGGS), the rigid linker (PAPAP) significantly increased the adsorption of the chimeric peptide on titanium surfaces (p chimeric peptide with the rigid linker exhibited more effective antimicrobial ability than the peptide with the flexible linker. This finding was ascribed to the ability of the rigid linker to separate functional domains and reduce their interference to the maximum extent. Consequently, the performance of chimeric peptides with specific titanium-binding motifs and antimicrobial motifs against bacteria can be optimized by the proper selection of linkers. This rational design of chimeric peptides provides a promising alternative to inhibit the formation of biofilms on titanium surfaces with the potential to prevent peri-implantitis and peri-implant mucositis.

Facile approach to the fabrication of a micropattern possessing nanoscale substructure.

Science.gov (United States)

Ji, Qiang; Jiang, Xuesong; Yin, Jie

2007-12-04

On the basis of the combined technologies of photolithography and reaction-induced phase separation (RIPS), a facile approach has been successfully developed for the fabrication of a micropattern possessing nanoscale substructure on the thin film surface. This approach involves three steps. In the first step, a thin film was prepared by spin coating from a solution of a commercial random copolymer, polystyrene-r-poly(methyl methacrylate) (PS-r-PMMA) and a commercial crosslinker, trimethylolpropane triacrylate (TMPTA). In the second step, photolithograph was performed with the thin film using a 250 W high-pressure mercury lamp to produce the micropattern. Finally, the resulting micropattern was annealed at 200 degrees C for a certain time, and reaction-induced phase separation occurred. After soaking in chloroform for 4 h, nanoscale substructure was obtained. The whole processes were traced by atomic force microscopy (AFM), X-ray photoelectron spectrometry (XPS), and Fourier transform infrared (FTIR) spectroscopy, and the results supported the proposed structure.

Fast and accurate protein substructure searching with simulated annealing and GPUs

Directory of Open Access Journals (Sweden)

Stivala Alex D

2010-09-01

Full Text Available Abstract Background Searching a database of protein structures for matches to a query structure, or occurrences of a structural motif, is an important task in structural biology and bioinformatics. While there are many existing methods for structural similarity searching, faster and more accurate approaches are still required, and few current methods are capable of substructure (motif searching. Results We developed an improved heuristic for tableau-based protein structure and substructure searching using simulated annealing, that is as fast or faster and comparable in accuracy, with some widely used existing methods. Furthermore, we created a parallel implementation on a modern graphics processing unit (GPU. Conclusions The GPU implementation achieves up to 34 times speedup over the CPU implementation of tableau-based structure search with simulated annealing, making it one of the fastest available methods. To the best of our knowledge, this is the first application of a GPU to the protein structural search problem.

Synthesis, DNA Binding, and Anticancer Properties of Bis-Naphthalimide Derivatives with Lysine-Modified Polyamine Linkers

Directory of Open Access Journals (Sweden)

Yu Huang

2018-01-01

Full Text Available A series of bis-naphthalimide derivatives with different diamine linkers were designed and synthesized. All of the synthesized bis-naphthalimide derivatives were characterized by NMR and HRMS spectra. The binding ability between the compounds and CT DNA was evaluated by using UV–Vis titration experiments. The bis-naphthalimide compound with an ethylenediamine linker showed the largest binding constant with CT DNA. Hence, it was used as the model compound to study the DNA binding selectivity by UV–Vis titration aiming at different DNA duplexes. As a result, this compound showed binding preference to AT-rich duplexes. The DNA binding modes of the compounds were also measured by viscosity titration. The cytotoxicity of the compounds was evaluated by MTT assay. Compounds with 1,6-diaminohexane or 1,4-phenylenedimethanamine linkers showed higher cytotoxicity compared with other bis-naphthalimide derivatives.

Linker histones: novel insights into structure-specific recognition of the nucleosome.

Science.gov (United States)

Cutter, Amber R; Hayes, Jeffrey J

2017-04-01

Linker histones (H1s) are a primary component of metazoan chromatin, fulfilling numerous functions, both in vitro and in vivo, including stabilizing the wrapping of DNA around the nucleosome, promoting folding and assembly of higher order chromatin structures, influencing nucleosome spacing on DNA, and regulating specific gene expression. However, many molecular details of how H1 binds to nucleosomes and recognizes unique structural features on the nucleosome surface remain undefined. Numerous, confounding studies are complicated not only by experimental limitations, but the use of different linker histone isoforms and nucleosome constructions. This review summarizes the decades of research that has resulted in several models of H1 association with nucleosomes, with a focus on recent advances that suggest multiple modes of H1 interaction in chromatin, while highlighting the remaining questions.

A New Achiral Linker Reagent for the Incorporation of Multiple Amino Groups Into Oligonucleotides

DEFF Research Database (Denmark)

1997-01-01

The present invention relates to a new functionalized achiral linker reagent for incorporating multiple primary amino groups or reporter groups into oligonucleotides following the phosphoramidite methodology. It is possible to substitute any ribodeoxynucleotide, deoxynucleotide, or nucleotide......-oxyl-2,2,5,5-tetramethylpyrrolidine), TEMPO (N-oxyl-2,2,6,6-tetramethylpiperidine), dinitrophenyl, texas red, tetramethyl rhodamine, 7-nitrobenzo-2-oxa-1-diazole (NBD), or pyrene. The present invention also relates to a solid phase support, e.g. a Controlled Pore Glass (CPG), immobilized linker reagent...

Ring and jet study on the azimuthal substructure of pions at CERN ...

Indian Academy of Sciences (India)

structures in the emission of secondary charged hadrons coming from 32S–Ag/Br interactions at 200 A GeV/c. Nuclear photographic emulsion technique has been employed to collect the experimental data. The presence of such substructures, ...

Substructure evolution of Zircaloy-4 during creep and implications for the Modified Jogged-Screw model

Energy Technology Data Exchange (ETDEWEB)

Morrow, B.M., E-mail: morrow@lanl.gov [The Ohio State University, 2041 College Rd., 477 Watts Hall, Columbus, OH 43210 (United States); Los Alamos National Laboratory, P.O. Box 1663, MS G755, Los Alamos, NM 87545 (United States); Kozar, R.W.; Anderson, K.R. [Bettis Laboratory, Bechtel Marine Propulsion Corp., West Mifflin, PA 15122 (United States); Mills, M.J., E-mail: millsmj@mse.osu.edu [The Ohio State University, 2041 College Rd., 477 Watts Hall, Columbus, OH 43210 (United States)

2016-05-17

Several specimens of Zircaloy-4 were creep tested at a single stress-temperature condition, and interrupted at different accumulated strain levels. Substructural observations were performed using bright field scanning transmission electron microscopy (BF STEM). The dislocation substructure was characterized to ascertain how creep strain evolution impacts the Modified Jogged-Screw (MJS) model, which has previously been utilized to predict steady-state strain rates in Zircaloy-4. Special attention was paid to the evolution of individual model parameters with increasing strain. Results of model parameter measurements are reported and discussed, along with possible extensions to the MJS model.

5-fold increase of hydrogen uptake in MOF74 through linker decorations

Science.gov (United States)

Thonhauser, T.; Zuluaga, S.; Harrison, D.; Welchman, E.; Arter, C.

We present ab initio results for linker decorations in Mg-MOF74-i.e. attaching various metals  = Li, Na, K, Sc, Cr, Mn, Fe, Ni, Cu, Zn, Rb, Pd, Ag, and Pt near the ring of the linker-creating new strong adsorption sites and thus maximizing small molecule uptake. We find that in most cases these decorations influence the overall form and structure of Mg-MOF74 only marginally. After the initial screening we chose metals that bind favorably to the linker and further investigate adsorption of H2, CO2, and H2O for  = Li, Na, K, and Sc. For the case of H2 we show that up to 24 additional guest molecules can be adsorbed in the MOF unit cell, with binding energies comparable to the original open-metal sites at the six corners of the channel. This leads to a 5-fold increase of the molecule uptake in Mg-MOF74, with tremendous impact on many applications in general and hydrogen storage in particular-where the gravimetric hydrogen density increases from 1 . 63 mass% to 7 . 28 mass% and the volumetric density from 15.10 g H2 L-1 to 75.50 g H2 L-1. This work was supported by NSF Grant No. DMR-1145968.

Temperature-triggered release of a liquid cross-linker micro-encapsulated in a glassy polymer for low temperature curing

NARCIS (Netherlands)

Senatore, D.; Cate, ten A.T.; Laven, J.; Benthem, van R.A.T.M.; With, de G.

2013-01-01

In order to prevent a liquid epoxy cross-linker from premature, Arrhenius-law predicted, reaction with an acid-functional polyester resin, the liquid cross-linker has been physically separated from the resin by encapsulation while release is only possible by a temperature-controlled trigger. The

Substructure formation in iron-nickel monocrystals at cellular growth

International Nuclear Information System (INIS)

Agapova, E.V.; Tagirova, D.M.

1984-01-01

Substructural perfection of Fe-31 wt.% Ni alloy crystals prepared by the Bridgeman method is investigated. Characteristics of banded and cellular structures at different morphology of crystallization front corresponding to the rates of growth (7.0-24.7)x10 -4 cm/s are determined. Position of disorientation axis of banded fragments is shown to depend on orientation of a groWing crystal and its strong fragmentation results in formation of finer cellular structure

Extremely stretchable thermosensitive hydrogels by introducing slide-ring polyrotaxane cross-linkers and ionic groups into the polymer network

Science.gov (United States)

Bin Imran, Abu; Esaki, Kenta; Gotoh, Hiroaki; Seki, Takahiro; Ito, Kohzo; Sakai, Yasuhiro; Takeoka, Yukikazu

2014-01-01

Stimuli-sensitive hydrogels changing their volumes and shapes in response to various stimulations have potential applications in multiple fields. However, these hydrogels have not yet been commercialized due to some problems that need to be overcome. One of the most significant problems is that conventional stimuli-sensitive hydrogels are usually brittle. Here we prepare extremely stretchable thermosensitive hydrogels with good toughness by using polyrotaxane derivatives composed of α-cyclodextrin and polyethylene glycol as cross-linkers and introducing ionic groups into the polymer network. The ionic groups help the polyrotaxane cross-linkers to become well extended in the polymer network. The resulting hydrogels are surprisingly stretchable and tough because the cross-linked α-cyclodextrin molecules can move along the polyethylene glycol chains. In addition, the polyrotaxane cross-linkers can be used with a variety of vinyl monomers; the mechanical properties of the wide variety of polymer gels can be improved by using these cross-linkers. PMID:25296246

Dynamics of Linker Residues Modulate the Nucleic Acid Binding Properties of the HIV-1 Nucleocapsid Protein Zinc Fingers

Science.gov (United States)

Zargarian, Loussiné; Tisné, Carine; Barraud, Pierre; Xu, Xiaoqian; Morellet, Nelly; René, Brigitte; Mély, Yves; Fossé, Philippe; Mauffret, Olivier

2014-01-01

The HIV-1 nucleocapsid protein (NC) is a small basic protein containing two zinc fingers (ZF) separated by a short linker. It is involved in several steps of the replication cycle and acts as a nucleic acid chaperone protein in facilitating nucleic acid strand transfers occurring during reverse transcription. Recent analysis of three-dimensional structures of NC-nucleic acids complexes established a new property: the unpaired guanines targeted by NC are more often inserted in the C-terminal zinc finger (ZF2) than in the N-terminal zinc finger (ZF1). Although previous NMR dynamic studies were performed with NC, the dynamic behavior of the linker residues connecting the two ZF domains remains unclear. This prompted us to investigate the dynamic behavior of the linker residues. Here, we collected 15N NMR relaxation data and used for the first time data at several fields to probe the protein dynamics. The analysis at two fields allows us to detect a slow motion occurring between the two domains around a hinge located in the linker at the G35 position. However, the amplitude of motion appears limited in our conditions. In addition, we showed that the neighboring linker residues R29, A30, P31, R32, K33 displayed restricted motion and numerous contacts with residues of ZF1. Our results are fully consistent with a model in which the ZF1-linker contacts prevent the ZF1 domain to interact with unpaired guanines, whereas the ZF2 domain is more accessible and competent to interact with unpaired guanines. In contrast, ZF1 with its large hydrophobic plateau is able to destabilize the double-stranded regions adjacent to the guanines bound by ZF2. The linker residues and the internal dynamics of NC regulate therefore the different functions of the two zinc fingers that are required for an optimal chaperone activity. PMID:25029439

Analysis of the state of the art of precast concrete bridge substructure systems.

Science.gov (United States)

2013-10-01

Precasting of bridge substructure components holds potential for accelerating the construction of bridges,reducing : impacts to the traveling public on routes adjacent to construction sites, improving bridge durability and hence service : life, and r...

Saccharomyces cerevisiae Linker Histone—Hho1p Maintains Chromatin Loop Organization during Ageing

Directory of Open Access Journals (Sweden)

Katya Uzunova

2013-01-01

Full Text Available Intricate, dynamic, and absolutely unavoidable ageing affects cells and organisms through their entire lifetime. Driven by diverse mechanisms all leading to compromised cellular functions and finally to death, this process is a challenge for researchers. The molecular mechanisms, the general rules that it follows, and the complex interplay at a molecular and cellular level are yet little understood. Here, we present our results showing a connection between the linker histones, the higher-order chromatin structures, and the process of chronological lifespan of yeast cells. By deleting the gene for the linker histone in Saccharomyces cerevisiae we have created a model for studying the role of chromatin structures mainly at its most elusive and so far barely understood higher-order levels of compaction in the processes of yeast chronological lifespan. The mutant cells demonstrated controversial features showing slower growth than the wild type combined with better survival during the whole process. The analysis of the global chromatin organization during different time points demonstrated certain loss of the upper levels of chromatin compaction in the cells without linker histone. The results underlay the importance of this histone for the maintenance of the chromatin loop structures during ageing.

Prefabricated floor panels composed of fiber reinforced concrete and a steel substructure

DEFF Research Database (Denmark)

Lárusson, Lárus H.; Fischer, Gregor; Jönsson, Jeppe

2013-01-01

This paper reports on a study on prefabricated composite and modular floor deck panels composed of relatively thin fiber reinforced concrete slabs connected to steel substructures. The study focuses on the design, manufacturing, structural improvements and behavior of the floor systems during...

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

Directory of Open Access Journals (Sweden)

Elisa Alonso-Perez

Full Text Available 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.

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

Science.gov (United States)

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

Impact of cathepsin B-sensitive triggers and hydrophilic linkers on in vitro efficacy of novel site-specific antibody-drug conjugates.

Science.gov (United States)

Bryden, Francesca; Martin, Camille; Letast, Stéphanie; Lles, Eva; Viéitez-Villemin, Inmaculada; Rousseau, Anaïs; Colas, Cyril; Brachet-Botineau, Marie; Allard-Vannier, Emilie; Larbouret, Christel; Viaud-Massuard, Marie-Claude; Joubert, Nicolas

2018-03-14

Herein we describe the synthesis and evaluation of four novel HER2-targeting, cathepsin B-sensitive antibody-drug conjugates bearing a monomethylauristatin E (MMAE) cytotoxic payload, constructed via the conjugation of cleavable linkers to trastuzumab using a site-specific bioconjugation methodology. These linkers vary by both cleavable trigger motif and hydrophilicity, containing one of two cathepsin B sensitive dipeptides (Val-Cit and Val-Ala), and engendered with either hydrophilic or hydrophobic character via application of a PEG 12 spacer. Through evaluation of physical properties, in vitro cytotoxicity, and receptor affinity of the resulting antibody-drug conjugates (ADCs), we have demonstrated that while both dipeptide triggers are effective, the increased hydrophobicity of the Val-Ala pair limits its utility within this type of linker. In addition, while PEGylation augments linker hydrophilicity, this change does not translate to more favourable ADC hydrophilicity or potency. While all described structures demonstrated excellent and similar in vitro cytotoxicity, the ADC with the ValCitPABMMAE linker shows the most promising combination of in vitro potency, structural homogeneity, and hydrophilicity, warranting further evaluation into its therapeutic potential.

Bifunctional bridging linker-assisted synthesis and characterization of TiO{sub 2}/Au nanocomposites

Energy Technology Data Exchange (ETDEWEB)

Žunič, Vojka, E-mail: vojka.zunic@ijs.si, E-mail: vojka13@gmail.com; Kurtjak, Mario; Suvorov, Danilo [Jožef Stefan Institute, Advanced Materials Department (Slovenia)

2016-11-15

Using a simple organic bifunctional bridging linker, titanium dioxide (TiO{sub 2}) nanoparticles were coupled with the Au nanoparticles to form TiO{sub 2}/Au nanocomposites with a variety of Au loadings. This organic bifunctional linker, meso-2,3-dimercaptosuccinic acid, contains two types of functional groups: (i) the carboxyl group, which enables binding to the TiO{sub 2}, and (ii) the thiol group, which enables binding to the Au. In addition, the organic bifunctional linker acts as a stabilizing agent to prevent the agglomeration and growth of the Au particles, resulting in the formation of highly dispersed Au nanoparticles. To form the TiO{sub 2}/Au nanocomposites in a simple way, we deliberately applied a synthetic method that simultaneously ensures: (i) the capping of the Au nanoparticles and (ii) the binding of different amounts of Au to the TiO{sub 2}. The TiO{sub 2}/Au nanocomposites formed with this method show enhanced UV and Vis photocatalytic activities when compared to the pure TiO{sub 2} nanopowders.Graphical Abstract.

Updating failure probability of a welded joint in offshore wind turbine substructures

DEFF Research Database (Denmark)

Mai, Quang A.; Sørensen, John Dalsgaard; Rigo, Philippe

2016-01-01

The operation and maintenance cost of offshore wind turbine substructures contributes significantly in the cost of a kWh. That cost may be lowered by application of reliability- and risk based maintenance strategies and reliability updating based on inspections performed during the design lifetim...

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

International Nuclear Information System (INIS)

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

1983-01-01

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

Iminodiacetic acid as bifunctional linker for dimerization of cyclic RGD peptides

International Nuclear Information System (INIS)

Xu, Dong; Zhao, Zuo-Quan; Chen, Shu-Ting; Yang, Yong; Fang, Wei; Liu, Shuang

2017-01-01

Introduction: In this study, I2P-RGD 2 was used as the example to illustrate a novel approach for dimerization of cyclic RGD peptides. The main objective of this study was to explore the impact of bifunctional linkers (glutamic acid vs. iminodiacetic acid) on tumor-targeting capability and excretion kinetics of the 99m Tc-labeled dimeric cyclic RGD peptides. Methods: HYNIC-I2P-RGD 2 was prepared by reacting I2P-RGD 2 with HYNIC-OSu in the presence of diisopropylethylamine, and was evaluated for its α v β 3 binding affinity against 125 I-echistatin bound to U87MG glioma cells. 99m Tc-I2P-RGD 2 was prepared with high specific activity (~185 GBq/μmol). The athymic nude mice bearing U87MG glioma xenografts were used to evaluate its biodistribution properties and image quality in comparison with those of 99m Tc-3P-RGD 2 . Results: The IC 50 value for HYNIC-I2P-RGD 2 was determined to be 39 ± 6 nM, which was very close to that (IC 50 = 33 ± 5 nM) of HYNIC-3P-RGD 2 . Replacing glutamic acid with iminodiacetic acid had little impact on α v β 3 binding affinity of cyclic RGD peptides. 99m Tc-I2P-RGD 2 and 99m Tc-3P-RGD 2 shared similar tumor uptake values over the 2 h period, and its α v β 3 -specificity was demonstrated by a blocking experiment. The uptake of 99m Tc-I2P-RGD 2 was significantly lower than 99m Tc-3P-RGD 2 in the liver and kidneys. The U87MG glioma tumors were visualized by SPECT with excellent contrast using both 99m Tc-I2P-RGD 2 and 99m Tc-3P-RGD 2 . Conclusion: Iminodiacetic acid is an excellent bifunctional linker for dimerization of cyclic RGD peptides. Bifunctional linkers have significant impact on the excretion kinetics of 99m Tc radiotracers. Because of its lower liver uptake and better tumor/liver ratios, 99m Tc-I2P-RGD 2 may have advantages over 99m Tc-3P-RGD 2 for diagnosis of tumors in chest region. -- Graphical abstract: This report presents novel approach for dimerization of cyclic RGD peptides using iminodiacetic acid as a

Exploring Milkyway Halo Substructures with Large-Area Sky Surveys

Energy Technology Data Exchange (ETDEWEB)

Li, Ting [Texas A & M Univ., College Station, TX (United States)

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

The S4-S5 linker acts as a signal integrator for HERG K+ channel activation and deactivation gating.

Directory of Open Access Journals (Sweden)

Chai Ann Ng

Full Text Available Human ether-à-go-go-related gene (hERG K(+ channels have unusual gating kinetics. Characterised by slow activation/deactivation but rapid inactivation/recovery from inactivation, the unique gating kinetics underlie the central role hERG channels play in cardiac repolarisation. The slow activation and deactivation kinetics are regulated in part by the S4-S5 linker, which couples movement of the voltage sensor domain to opening of the activation gate at the distal end of the inner helix of the pore domain. It has also been suggested that cytosolic domains may interact with the S4-S5 linker to regulate activation and deactivation kinetics. Here, we show that the solution structure of a peptide corresponding to the S4-S5 linker of hERG contains an amphipathic helix. The effects of mutations at the majority of residues in the S4-S5 linker of hERG were consistent with the previously identified role in coupling voltage sensor movement to the activation gate. However, mutations to Ser543, Tyr545, Gly546 and Ala548 had more complex phenotypes indicating that these residues are involved in additional interactions. We propose a model in which the S4-S5 linker, in addition to coupling VSD movement to the activation gate, also contributes to interactions that stabilise the closed state and a separate set of interactions that stabilise the open state. The S4-S5 linker therefore acts as a signal integrator and plays a crucial role in the slow deactivation kinetics of the channel.

Reheating effects in the matter power spectrum and implications for substructure

International Nuclear Information System (INIS)

Erickcek, Adrienne L.; Sigurdson, Kris

2011-01-01

The thermal and expansion history of the Universe before big bang nucleosynthesis is unknown. We investigate the evolution of cosmological perturbations through the transition from an early matter era to radiation domination. We treat reheating as the perturbative decay of an oscillating scalar field into relativistic plasma and cold dark matter. After reheating, we find that subhorizon perturbations in the decay-produced dark matter density are significantly enhanced, while subhorizon radiation perturbations are instead suppressed. If dark matter originates in the radiation bath after reheating, this suppression may be the primary cutoff in the matter power spectrum. Conversely, for dark matter produced nonthermally from scalar decay, enhanced perturbations can drive structure formation during the cosmic dark ages and dramatically increase the abundance of compact substructures. For low reheat temperatures, we find that as much as 50% of all dark matter is in microhalos with M > or approx. 0.1M + at z≅100, compared to a fraction of ∼10 -10 in the standard case. In this scenario, ultradense substructures may constitute a large fraction of dark matter in galaxies today.

Onset of grain filling is associated with a change in properties of linker histone variants in maize kernels

DEFF Research Database (Denmark)

Kalamajka, R.; Finnie, Christine; Grasser, K.D.

2010-01-01

) initiation of storage synthesis. Six linker histone gene products were identified by MALDI-TOF mass spectrometry. A marked shift of around 4 pH units was observed for the linker histone spot pattern after 2D-gel electrophoresis when comparing the proteins of 11 and 16 dap kernels. The shift from acidic...

Substructures developed during creep and cyclic tests of type 304 stainless steel (heat 9T2796)

International Nuclear Information System (INIS)

Swindeman, R.W.; Bhargava, R.K.; Sikka, V.K.; Moteff, J.

1977-09-01

Substructures developed in tested specimens of a reference heat of type 304 stainless steel (heat 9T2796) are examined. Data include dislocation densities, cell and subgrain sizes, and carbide precipitate sizes. Testing conditions range for temperatures from 482 to 649 0 C, for stresses from 28 to 241 MPa, and for times from 4 to 15,000 hr. As expected, it is observed that temperature, stress, and time have strong influences on substructure. The change in the dislocation density is too small to measure for conditions which produce less than 1 percent monotonic strain. No cells form, and the major alteration of substructure is the precipitation of M 23 C 6 carbides on grain boundaries, on twin boundaries, and on some dislocations. At stresses ranging from 69 to 172 MPa and at temperatures ranging from 482 to 593 0 C, the dislocation density increases with increasing stress and is generally higher than expected from studies made at higher temperatures. Dislocations are arranged in fine networks stabilized by carbides. At stresses above 172 MPa and temperatures to 649 0 C, the dislocation density is too great to measure. Cells develop which are finer in size than cells developed at similar stresses but at higher temperatures. Dislocation densities and cell sizes for cyclic specimens are comparable to data for creep-tested specimens. On the basis of the observed substructures, recommendations are made regarding further studies which would assist in the development of constitutive equations for high-temperature inelastic analysis of reactor components

Synthesis of two new alkyne-bearing linkers used for the preparation of siRNA for labeling by click chemistry with fluorine-18

International Nuclear Information System (INIS)

Flagothier, Jessica; Kaisin, Geoffroy; Mercier, Frederic; Thonon, David; Teller, Nathalie; Wouters, Johan; Luxen, André

2012-01-01

Oligonucleotides (ONs) and more particularly siRNAs are promising drugs but their pharmacokinetics and biodistribution are widely unknown. Positron Emission Tomography (PET) using fluorine-18 is a suitable technique to quantify these biological processes. Click chemistry (Huisgen cycloaddition) is the current method for labeling siRNA. In order to study the influence of a linker bearing by [ 18 F] labeled ONs, on the in vivo pharmacokinetic and metabolism, we have developed two modified ONs by two new linkers. Here we report the synthesis of two alkyne-bearing linkers, the incorporation onto a ONs and the conjugation by click chemistry with a [ 18 F] prosthetic group. - Highlights: ► Synthesis of two new alkyne linkers. ► Functionalization at the 3′-end siRNA by alkyne linker derived of proline. ► Click chemistry between alkyne modified siRNA and [ 18 F] prosthetic group.

The Substructure of the Solar Corona Observed in the Hi-C Telescope

Science.gov (United States)

Winebarger, A.; Cirtain, J.; Golub, L.; DeLuca, E.; Savage, S.; Alexander, C.; Schuler, T.

2014-01-01

In the summer of 2012, the High-resolution Coronal Imager (Hi-C) flew aboard a NASA sounding rocket and collected the highest spatial resolution images ever obtained of the solar corona. One of the goals of the Hi-C flight was to characterize the substructure of the solar corona. We therefore calculate how the intensity scales from a low-resolution (AIA) pixels to high-resolution (Hi-C) pixels for both the dynamic events and "background" emission (meaning, the steady emission over the 5 minutes of data acquisition time). We find there is no evidence of substructure in the background corona; the intensity scales smoothly from low-resolution to high-resolution Hi-C pixels. In transient events, however, the intensity observed with Hi-C is, on average, 2.6 times larger than observed with AIA. This increase in intensity suggests that AIA is not resolving these events. This result suggests a finely structured dynamic corona embedded in a smoothly varying background.

Crystallization and preliminary X-ray analysis of Acetivibrio cellulolyticus cellulosomal type II cohesin module: two versions having different linker lengths

International Nuclear Information System (INIS)

Noach, Ilit; Alber, Orly; Bayer, Edward A.; Lamed, Raphael; Levy-Assaraf, Maly; Shimon, Linda J. W.; Frolow, Felix

2007-01-01

The cloning, expression, purification, crystallization and preliminary X-ray characterization of two protein constructs of the second type II cohesin module from A. cellulolyticus ScaB are described. Both constructs contain the native N-terminal linker, but only one of them contains the full-length 45-residue C-terminal linker; the other contains a five-residue segment of this linker. The second type II cohesin module of the cellulosomal scaffoldin polypeptide ScaB from Acetivibrio cellulolyticus (CohB2) was cloned into two constructs: one containing a short (five-residue) C-terminal linker (CohB2-S) and the second incorporating the full native 45-residue linker (CohB2-L). Both constructs encode proteins that also include the full native six-residue N-terminal linker. The CohB2-S and CohB2-L proteins were expressed, purified and crystallized in the orthorhombic crystal system, but with different unit cells and symmetries: space group P2 1 2 1 2 1 with unit-cell parameters a = 90.36, b = 68.65, c = 111.29 Å for CohB2-S and space group P2 1 2 1 2 with unit-cell parameters a = 68.76, b = 159.22, c = 44.21 Å for CohB2-L. The crystals diffracted to 2.0 and 2.9 Å resolution, respectively. The asymmetric unit of CohB2-S contains three cohesin molecules, while that of CohB2-L contains two molecules

CLOSE STELLAR ENCOUNTERS IN YOUNG, SUBSTRUCTURED, DISSOLVING STAR CLUSTERS: STATISTICS AND EFFECTS ON PLANETARY SYSTEMS

International Nuclear Information System (INIS)

Craig, Jonathan; Krumholz, Mark R.

2013-01-01

Both simulations and observations indicate that stars form in filamentary, hierarchically clustered associations, most of which disperse into their galactic field once feedback destroys their parent clouds. However, during their early evolution in these substructured environments, stars can undergo close encounters with one another that might have significant impacts on their protoplanetary disks or young planetary systems. We perform N-body simulations of the early evolution of dissolving, substructured clusters with a wide range of properties, with the aim of quantifying the expected number and orbital element distributions of encounters as a function of cluster properties. We show that the presence of substructure both boosts the encounter rate and modifies the distribution of encounter velocities compared to what would be expected for a dynamically relaxed cluster. However, the boost only lasts for a dynamical time, and as a result the overall number of encounters expected remains low enough that gravitational stripping is unlikely to be a significant effect for the vast majority of star-forming environments in the Galaxy. We briefly discuss the implications of this result for models of the origin of the solar system, and of free-floating planets. We also provide tabulated encounter rates and orbital element distributions suitable for inclusion in population synthesis models of planet formation in a clustered environment.

CLOSE STELLAR ENCOUNTERS IN YOUNG, SUBSTRUCTURED, DISSOLVING STAR CLUSTERS: STATISTICS AND EFFECTS ON PLANETARY SYSTEMS

Energy Technology Data Exchange (ETDEWEB)

Craig, Jonathan; Krumholz, Mark R., E-mail: krumholz@ucolick.org [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States)

2013-06-01

Both simulations and observations indicate that stars form in filamentary, hierarchically clustered associations, most of which disperse into their galactic field once feedback destroys their parent clouds. However, during their early evolution in these substructured environments, stars can undergo close encounters with one another that might have significant impacts on their protoplanetary disks or young planetary systems. We perform N-body simulations of the early evolution of dissolving, substructured clusters with a wide range of properties, with the aim of quantifying the expected number and orbital element distributions of encounters as a function of cluster properties. We show that the presence of substructure both boosts the encounter rate and modifies the distribution of encounter velocities compared to what would be expected for a dynamically relaxed cluster. However, the boost only lasts for a dynamical time, and as a result the overall number of encounters expected remains low enough that gravitational stripping is unlikely to be a significant effect for the vast majority of star-forming environments in the Galaxy. We briefly discuss the implications of this result for models of the origin of the solar system, and of free-floating planets. We also provide tabulated encounter rates and orbital element distributions suitable for inclusion in population synthesis models of planet formation in a clustered environment.

Close Stellar Encounters in Young, Substructured, Dissolving Star Clusters: Statistics and Effects on Planetary Systems

Science.gov (United States)

Craig, Jonathan; Krumholz, Mark R.

2013-06-01

Both simulations and observations indicate that stars form in filamentary, hierarchically clustered associations, most of which disperse into their galactic field once feedback destroys their parent clouds. However, during their early evolution in these substructured environments, stars can undergo close encounters with one another that might have significant impacts on their protoplanetary disks or young planetary systems. We perform N-body simulations of the early evolution of dissolving, substructured clusters with a wide range of properties, with the aim of quantifying the expected number and orbital element distributions of encounters as a function of cluster properties. We show that the presence of substructure both boosts the encounter rate and modifies the distribution of encounter velocities compared to what would be expected for a dynamically relaxed cluster. However, the boost only lasts for a dynamical time, and as a result the overall number of encounters expected remains low enough that gravitational stripping is unlikely to be a significant effect for the vast majority of star-forming environments in the Galaxy. We briefly discuss the implications of this result for models of the origin of the solar system, and of free-floating planets. We also provide tabulated encounter rates and orbital element distributions suitable for inclusion in population synthesis models of planet formation in a clustered environment.

Seasonal variations of radon concentrations in single-family houses with different sub-structures

DEFF Research Database (Denmark)

Majborn, B.

1992-01-01

Seasonal variations of indoor radon concentrations have been studied in 70 single-family houses selected according to the type of sub-structure and the type of soil underneath the house. Five categories of sub-structure were included - slab-on-grade, crawl space, basement, and combinations...... of basement with slab-on-grade or crawl space. Half of the houses are located on clayey till and the other half on glaciofluvial gravel. In each house radon was measured in a living room and a bedroom, in the basement if present, and in the crawl space if present and accessible. The measurements were made...... with track detectors on a quarterly basis throughout a year. For living rooms and bedrooms the seasonal variations range from being highly significant for the slab-on-grade houses to being insignificant for the crawl space houses. For basements and crawl spaces the geometric mean radon concentrations do...

Analysis of random response of structure with uncertain parameters. Combination of substructure synthesis method and hierarchy method

International Nuclear Information System (INIS)

Iwatsubo, Takuzo; Kawamura, Shozo; Mori, Hiroyuki.

1995-01-01

In this paper, the method to obtain the random response of a structure with uncertain parameters is proposed. The proposed method is a combination of the substructure synthesis method and the hierarchy method. The concept of the proposed method is that the hierarchy equation of each substructure is obtained using the hierarchy method, and the hierarchy equation of the overall structure is obtained using the substructure synthesis method. Using the proposed method, the reduced order hierarchy equation can be obtained without analyzing the original whole structure. After the calculation of the mean square value of response, the reliability analysis can be carried out based on the first passage problem and Poisson's excursion rate. As a numerical example of structure, a simple piping system is considered. The damping constant of the support is considered as the uncertainty parameter. Then the random response is calculated using the proposed method. As a result, the proposed method is useful to analyze the random response in terms of the accuracy, computer storage and calculation time. (author)

Mechanical strenght and niobium and niobium-base alloys substructures

International Nuclear Information System (INIS)

Monteiro, W.A.; Andrade, A.H.P. de

1986-01-01

Niobium and some of its alloys have been used in several fields of technological applications such as the aerospace, chemical and nuclear industries. This is due to its excelent mechanical stringth at high temperatures and reasonable ductility at low temperatures. In this work, we review the main features of the relationship mechanical strength - substructure in niobium and its alloys, taking into account the presence of impurities, the influence of initial thermal and thermo - mechanical treatments as well as the irradiation by energetic particles. (Author) [pt

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

Science.gov (United States)

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.

Searching for dwarf spheroidal galaxies and other galactic dark matter substructures with the Fermi large area telescope

Energy Technology Data Exchange (ETDEWEB)

Drlica-Wagner, Alex [Stanford Univ., CA (United States). Dept. of Physics

2013-08-01

Over the past century, it has become clear that about a quarter of the known universe is composed of an invisible, massive component termed ''dark matter''. Some of the most popular theories of physics beyond the Standard Model suggest that dark matter may be a new fundamental particle that could self-annihilate to produce γ rays. Nearby over-densities in the dark matter halo of our Milky Way present some of the most promising targets for detecting the annihilation of dark matter. We used the Large Area Telescope (LAT) on-board the Fermi Gamma-ray Space Telescope to search for γ rays produced by dark matter annihilation in Galactic dark matter substructures. We searched for γ-ray emission coincident with Milky Way dwarf spheroidal satellite galaxies, which trace the most massive Galactic dark matter substructures. We also sought to identify nearby dark matter substructures that lack all astrophysical tracers and would be detectable only through γ-ray emission from dark matter annihilation. We found no conclusive evidence for γ-ray emission from dark matter annihilation, and we set stringent and robust constraints on the dark matter annihilation cross section. While γ-ray searches for dark matter substructure are currently the most sensitive and robust probes of dark matter annihilation, they are just beginning to intersect the theoretically preferred region of dark matter parameter space. Thus, we consider future prospects for increasing the sensitivity of γ-ray searches through improvements to the LAT instrument performance and through upcoming wide- field optical surveys.

The linker domain of poly(rC) binding protein 2 is a major determinant in poliovirus cap-independent translation.

Science.gov (United States)

Sean, Polen; Nguyen, Joseph H C; Semler, Bert L

2008-09-01

Poliovirus, a member of the enterovirus genus in the family Picornaviridae, is the causative agent of poliomyelitis. Translation of the viral genome is mediated through an internal ribosomal entry site (IRES) encoded within the 5' noncoding region (5' NCR). IRES elements are highly structured RNA sequences that facilitate the recruitment of ribosomes for translation. Previous studies have shown that binding of a cellular protein, poly(rC) binding protein 2 (PCBP2), to a major stem-loop structure in the genomic 5' NCR is necessary for the translation of picornaviruses containing type I IRES elements, including poliovirus, coxsackievirus, and human rhinovirus. PCBP1, an isoform that shares approximately 90% amino acid identity to PCBP2, cannot efficiently stimulate poliovirus IRES-mediated translation, most likely due to its reduced binding affinity to stem-loop IV within the poliovirus IRES. The primary differences between PCBP1 and PCBP2 are found in the so-called linker domain between the second and third K-homology (KH) domains of these proteins. We hypothesize that the linker region of PCBP2 augments binding to poliovirus stem-loop IV RNA. To test this hypothesis, we generated six PCBP1/PCBP2 chimeric proteins. The recombinant PCBP1/PCBP2 chimeric proteins were able to interact with poliovirus stem-loop I RNA and participate in protein-protein interactions. We demonstrated that the PCBP1/PCBP2 chimeric proteins with the PCBP2 linker, but not with the PCBP1 linker, were able to interact with poliovirus stem-loop IV RNA, and could subsequently stimulate poliovirus IRES-mediated translation. In addition, using a monoclonal anti-PCBP2 antibody (directed against the PCBP2 linker domain) in mobility shift assays, we showed that the PCBP2 linker domain modulates binding to poliovirus stem-loop IV RNA via a mechanism that is not inhibited by the antibody.

Polyamorphism and substructure of short-range order in amorphous boron films

International Nuclear Information System (INIS)

Palatnik, L.S.; Nechitajlo, A.A.; Koz'ma, A.A.

1981-01-01

The structure and substructure of boron amorphous films are studied in detail. Amorphous condensate of Bsup(a) boron is built of the same (but only disorientedly located) 12 B icosahedrons as boron crystalline modifications: B 105 -equilibrium β-rhombic, metastable: B 50 -tetragonal, B 12 -α-rhombohedral Coordination number for Bsup(a) (Z 1 =6.4) is lower than in B 105 (Z 1 =6.6) but higher than in B 50 modification (Z 1 =6.1). In crystalline modifications B 105 , B 50 , B 12 coordination numbers ω in first coordination spheres of icosahedrons are equal to ν 105 =6+4.6=10.6; ν 50 =10+3=14; ν 12 =6 respectively. Both amorphous modifications of boron Bsub(1)sup(a) and Bsub(15)sup(a) are analogs to B 50 in respect of the short-range order of icosahedron location. The difference between them is in ''substructure'' of short-range order: part of boron atoms (approximately 12%) do not occupy the vertices (so that vacancies appear) and enter the emptinesses between icosahedrons. In other words, the structure B 50 is the model basis of both amorphous phases [ru

A Linker for the Solid-Phase Synthesis of Hydroxamic Acids and Identification of HDAC6 Inhibitors

DEFF Research Database (Denmark)

Bang, Claus Gunnar; Jensen, Jakob Feldthusen; Cohrt, Anders Emil O'Hanlon

2017-01-01

We herein present broadly useful, readily available and nonintegral hydroxylamine linkers for the routine solid-phase synthesis of hydroxamic acids. The developed protocols enable the efficient synthesis and release of a wide range of hydroxamic acids from various resins, relying on high control...... and flexibility with respect to reagents and synthetic processes. A trityl-based hydroxylamine linker was used to synthesize a library of peptide hydroxamic acids. The inhibitory effects of the compounds were examined for seven HDAC enzyme subtypes using a chemiluminescence-based assay....

3D Representative Volume Element Reconstruction of Fiber Composites via Orientation Tensor and Substructure Features

Energy Technology Data Exchange (ETDEWEB)

Li, Yi; Chen, Wei; Xu, Hongyi; Jin, Xuejun

2016-01-01

To provide a seamless integration of manufacturing processing simulation and fiber microstructure modeling, two new stochastic 3D microstructure reconstruction methods are proposed for two types of random fiber composites: random short fiber composites, and Sheet Molding Compounds (SMC) chopped fiber composites. A Random Sequential Adsorption (RSA) algorithm is first developed to embed statistical orientation information into 3D RVE reconstruction of random short fiber composites. For the SMC composites, an optimized Voronoi diagram based approach is developed for capturing the substructure features of SMC chopped fiber composites. The proposed methods are distinguished from other reconstruction works by providing a way of integrating statistical information (fiber orientation tensor) obtained from material processing simulation, as well as capturing the multiscale substructures of the SMC composites.

Desorption of 3,3′-diindolylmethane from imprinted particles: An impact of cross-linker structure on binding capacity and selectivity

Energy Technology Data Exchange (ETDEWEB)

Klejn, Dorota; Luliński, Piotr; Maciejewska, Dorota, E-mail: dorota.maciejewska@wum.edu.pl

2015-11-01

Here, seven cross-linkers (six polar diacrylates or dimethacrylates of different lengths between double bonds, and one aromatic-divinylbenzene) were used to examine the impact of the cross-linker on binding capacity and selectivity of 3,3′-diindolylmethane (DIM) imprinted material. DIM participates in the suppression of viability of human ovarian and human breast cancer cell lines, but has low bioavailability. The investigations of novel imprinted polymer matrices for improvement of DIM release could allow to utilize not only a potency of DIM but also similar alkaloids, which are the important compounds with pharmacological activity. The bulk, thermal radical copolymerization of the cross-linkers in the presence of 3,3′-diindolylmethane (the template) and allylamine (the functional monomer) in dimethyl sulfoxide or in carbon tetrachloride (porogens) was carried out. The binding capacities of imprinted and non-imprinted polymers were compared, and two polymers (these were prepared using ethylene glycol dimethacrylate and polyethylene glycol dimethacrylate as the cross-linkers) with the highest selectivity and binding capacity were selected to desorption test. The desorption profile of polymer prepared using polyethylene glycol dimethacrylate as the cross-linker revealed sustained release of 3,3′-diindolylmethane, and this system was selected for further optimization of the cross-linker amounts. The morphology and structure of the selected particles were analyzed using SEM micrographs, {sup 13}C CP/MAS NMR spectroscopy, and BET measurements. The desorption of 3,3′-diindolylmethane from poly(allylamine-co-polyethylene glycol dimethacrylate) particles was in accordance with pseudo-second-order kinetics and the simplified Higuchi model indicated the diffusion controlled release of 3,3′-diindolylmethane. - Graphical abstract: Sustained release of 3,3′-diindolylmethane from cavity in imprinted poly(allylamine-co-polyethylene glycol dimethacrylate

Desorption of 3,3′-diindolylmethane from imprinted particles: An impact of cross-linker structure on binding capacity and selectivity

International Nuclear Information System (INIS)

Klejn, Dorota; Luliński, Piotr; Maciejewska, Dorota

2015-01-01

Here, seven cross-linkers (six polar diacrylates or dimethacrylates of different lengths between double bonds, and one aromatic-divinylbenzene) were used to examine the impact of the cross-linker on binding capacity and selectivity of 3,3′-diindolylmethane (DIM) imprinted material. DIM participates in the suppression of viability of human ovarian and human breast cancer cell lines, but has low bioavailability. The investigations of novel imprinted polymer matrices for improvement of DIM release could allow to utilize not only a potency of DIM but also similar alkaloids, which are the important compounds with pharmacological activity. The bulk, thermal radical copolymerization of the cross-linkers in the presence of 3,3′-diindolylmethane (the template) and allylamine (the functional monomer) in dimethyl sulfoxide or in carbon tetrachloride (porogens) was carried out. The binding capacities of imprinted and non-imprinted polymers were compared, and two polymers (these were prepared using ethylene glycol dimethacrylate and polyethylene glycol dimethacrylate as the cross-linkers) with the highest selectivity and binding capacity were selected to desorption test. The desorption profile of polymer prepared using polyethylene glycol dimethacrylate as the cross-linker revealed sustained release of 3,3′-diindolylmethane, and this system was selected for further optimization of the cross-linker amounts. The morphology and structure of the selected particles were analyzed using SEM micrographs, 13 C CP/MAS NMR spectroscopy, and BET measurements. The desorption of 3,3′-diindolylmethane from poly(allylamine-co-polyethylene glycol dimethacrylate) particles was in accordance with pseudo-second-order kinetics and the simplified Higuchi model indicated the diffusion controlled release of 3,3′-diindolylmethane. - Graphical abstract: Sustained release of 3,3′-diindolylmethane from cavity in imprinted poly(allylamine-co-polyethylene glycol dimethacrylate). - Highlights: �

High-resolution two-dimensional liquid chromatography analysis of key linker drug intermediate used in antibody drug conjugates.

Science.gov (United States)

Venkatramani, C J; Huang, Shu Rong; Al-Sayah, Mohammad; Patel, Ila; Wigman, Larry

2017-10-27

In this manuscript, the application of high-resolution sampling (HRS) two-dimensional liquid chromatography (2D-LC) in the detailed analysis of key linker drug intermediate is presented. Using HRS, selected regions of the primary column eluent were transferred to a secondary column with fidelity enabling qualitative and quantitative analysis of linker drugs. The primary column purity of linker drug intermediate ranged from 88.9% to 94.5% and the secondary column purity ranged from 99.6% to 99.9%, showing lot-to-lot variability, significant differences between the three lots, and substantiating the synthetic and analytical challenges of ADCs. Over 15 impurities co-eluting with the linker drug intermediate in the primary dimension were resolved in the secondary dimension. The concentrations of most of these impurities were over three orders of magnitude lower than the linker drug. Effective peak focusing and high-speed secondary column analysis resulted in sharp peaks in the secondary dimension, improving the signal-to-noise ratios. The sensitivity of 2D-LC separation was over five fold better than conventional HPLC separation. The limit of quantitation (LOQ) was less than 0.01%. Many peaks originating from primary dimension were resolved into multiple components in the complementary secondary dimension, demonstrating the complexity of these samples. The 2D-LC was highly reproducible, showing good precision between runs with%RSD of peak areas less than 0.1 for the main component. The absolute difference in the peak areas of impurities less than 0.1% were within ±0.01% and for impurities in the range of 0.1%-0.3%, the absolute difference were ±0.02%, which are comparable to 1D-LC. The overall purity of the linker drug intermediate was determined from the product of primary and secondary column purity (HPLC Purity=%peak area of main component in the primary dimension×%peak area of main component in the secondary dimension). Additionally, the 2D-LC separation enables

The Next Generation Virgo Cluster Survey (NGVS). XXXII. A Search for Globular Cluster Substructures in the Virgo Galaxy Cluster Core

Science.gov (United States)

Powalka, Mathieu; Puzia, Thomas H.; Lançon, Ariane; Longobardi, Alessia; Peng, Eric W.; Duc, Pierre-Alain; Alamo-Martínez, Karla; Blakeslee, John P.; Côté, Patrick; Cuillandre, Jean-Charles; Durrell, Patrick; Eigenthaler, Paul; Ferrarese, Laura; Guhathakurta, Puragra; Gwyn, S. D. J.; Hudelot, Patrick; Liu, Chengze; Mei, Simona; Muñoz, Roberto P.; Roediger, Joel; Sánchez-Janssen, Rubén; Toloba, Elisa; Zhang, Hongxin

2018-03-01

Substructure in globular cluster (GC) populations around large galaxies is expected in galaxy formation scenarios that involve accretion or merger events, and it has been searched for using direct associations between GCs and structure in the diffuse galaxy light, or with GC kinematics. Here, we present a search for candidate substructures in the GC population around the Virgo cD galaxy M87 through the analysis of the spatial distribution of the GC colors. The study is based on a sample of ∼1800 bright GCs with high-quality u, g, r, i, z, K s photometry, selected to ensure a low contamination by foreground stars or background galaxies. The spectral energy distributions of the GCs are associated with formal estimates of age and metallicity, which are representative of its position in a 4D color space relative to standard single stellar population models. Dividing the sample into broad bins based on the relative formal ages, we observe inhomogeneities that reveal signatures of GC substructures. The most significant of these is a spatial overdensity of GCs with relatively young age labels, of diameter ∼0.°1 (∼30 kpc), located to the south of M87. The significance of this detection is larger than about 5σ after accounting for estimates of random and systematic errors. Surprisingly, no large Virgo galaxy is present in this area that could potentially host these GCs. But candidate substructures in the M87 halo with equally elusive hosts have been described based on kinematic studies in the past. The number of GC spectra available around M87 is currently insufficient to clarify the nature of the new candidate substructure.

Performance of large-R jets and jet substructure reconstruction with the ATLAS detector

CERN Document Server

The ATLAS collaboration

2012-01-01

This paper presents the application of techniques to study jet substructure. The performance of modified jet algorithms for a variety of jet types and event topologies is investigated. Properties of jets subjected to the mass-drop filtering, trimming and pruning algorithms are found to have a reduced sensitivity to multiple proton-proton interactions and exhibit improved stability at high luminosity. Monte Carlo studies of the signal-background discrimination with jet grooming in new physics searches based on jet invariant mass and jet substructure properties are also presented. The application of jet trimming is shown to improve the robustness of large-R jet measurements, reduce sensitivity to the superfluous effects due to the intense environment of the high luminosity LHC, and improve the physics potential of searches for heavy boosted objects. The analyses presented in this note use the full 2011 ATLAS dataset, corresponding to an integrated luminosity of 4.7 \\pm 0.2 fb−1 .

Investigation of the Linker Swing Motion in the Zeolitic Imidazolate Framework ZIF-90

KAUST Repository

Zheng, Bin; Fu, Fang; Wang, Lian Li; Yang, Limin; Zhu, Yihan; Du, Huiling

2018-01-01

The linker swing motion in the zeolitic imidazolate framework ZIF-90 is investigated by density functional theory (DFT) calculation, molecular dynamics (MD) and grand-canonical Monte Carlo (GCMC) simulations. The relation between the terminal

Evaluation of ¹¹¹in-labelled exendin-4 derivatives containing different meprin β-specific cleavable linkers.

Directory of Open Access Journals (Sweden)

Andreas Jodal

Full Text Available Cleavable linkers, which are specifically cleaved by defined conditions or enzymes, are powerful tools that can be used for various purposes. Amongst other things, they have been successfully used to deliver toxic payloads as prodrugs into target tissues. In this work novel linker sequences targeting meprin β, a metalloprotease expressed in the kidney brush-border membrane, were designed and included in the sequence of three radiolabelled exendin-4 derivatives. As radiolabelled exendin-4 derivatives strongly accumulate in the kidneys, we hypothesised that specific cleavage of the radiolabelled moiety at the kidney brush-border membrane would allow easier excretion of the activity into the urine and therefore improve the pharmacological properties of the peptide.The insertion of a cleavable linker did not negatively influence the in vitro properties of the peptides. They showed a good affinity to the GLP-1 receptor expressed in CHL cells, a high internalisation and sufficiently high stability in fresh human blood plasma. In vitro digestion with recombinant meprin β rapidly metabolised the corresponding linker sequences. After 60 min the majority of the corresponding peptides were digested and at the same time the anticipated fragments were formed. The peptides were also quickly metabolised in CD1 nu/nu mouse kidney homogenates. Immunofluorescence staining of meprin β in kidney sections confirmed the expression of the protease in the kidney brush-border membrane. Biodistribution in GLP-1 receptor positive tumour-xenograft bearing mice revealed high specific uptake of the 111In-labelled tracers in receptor positive tissue. Accumulation in the kidneys, however, was still high and comparable to the lead compound 111In-Ex4NOD40.In conclusion, we show that the concept of cleavable linkers specific for meprin β is feasible, as the peptides are rapidly cleaved by the enzyme while retaining their biological properties.

The H1 linker histones: multifunctional proteins beyond the nucleosomal core particle.

Science.gov (United States)

Hergeth, Sonja P; Schneider, Robert

2015-11-01

The linker histone H1 family members are a key component of chromatin and bind to the nucleosomal core particle around the DNA entry and exit sites. H1 can stabilize both nucleosome structure and higher-order chromatin architecture. In general, H1 molecules consist of a central globular domain with more flexible tail regions at both their N- and C-terminal ends. The existence of multiple H1 subtypes and a large variety of posttranslational modifications brings about a considerable degree of complexity and makes studying this protein family challenging. Here, we review recent progress in understanding the function of linker histones and their subtypes beyond their role as merely structural chromatin components. We summarize current findings on the role of H1 in heterochromatin formation, transcriptional regulation and embryogenesis with a focus on H1 subtypes and their specific modifications. © 2015 The Authors.

Efficient Naphthalenediimide-Based Hole Semiconducting Polymer with Vinylene Linkers between Donor and Acceptor Units

KAUST Repository

Zhang, Lei

2016-11-04

We demonstrate a new method to reverse the polarity and charge transport behavior of naphthalenediimide (NDI)-based copolymers by inserting a vinylene linker between the donor and acceptor units. The vinylene linkers minimize the intrinsic steric congestion between the NDI and thiophene moieties to prompt backbone planarity. The polymers with vinylene linkers exhibit electron n-channel transport characteristics under vacuum, similar to the benchmark polymer, P(NDI2OD-T2). To our surprise, when the polymers are measured in air, the dominant carrier type switches from n- to p-type and yield hole mobilities up to 0.45 cm(2) s(-1) with hole to electron mobility ratio of three (mu(h)/mu(e), similar to 3), which indicates that the hole density in the active layer can be significantly increased by exposure to air. This increase is consistent with the intrinsic more delocalized nature of the highest occupied molecular orbital of the charged vinylene polymer, as estimated by density functional theory (DFT) calculations, which facilitates hole transport within the polymer chains. This is the first demonstration of an efficient NDI-based hole semiconducting polymer, which will enable new developments in all-polymer solar cells, complementary circuits, and dopable polymers for use in thermoelectrics.

Efficient Naphthalenediimide-Based Hole Semiconducting Polymer with Vinylene Linkers between Donor and Acceptor Units

KAUST Repository

Zhang, Lei; Rose, Bradley Daniel; Liu, Yao; Nahid, Masrur M.; Gann, Eliot; Ly, Jack; Zhao, Wei; Rosa, Stephen J.; Russell, Thomas P.; Facchetti, Antonio; McNei, Christopher R.; Bredas, Jean-Luc; Briseno, Alejandro L.

2016-01-01

We demonstrate a new method to reverse the polarity and charge transport behavior of naphthalenediimide (NDI)-based copolymers by inserting a vinylene linker between the donor and acceptor units. The vinylene linkers minimize the intrinsic steric congestion between the NDI and thiophene moieties to prompt backbone planarity. The polymers with vinylene linkers exhibit electron n-channel transport characteristics under vacuum, similar to the benchmark polymer, P(NDI2OD-T2). To our surprise, when the polymers are measured in air, the dominant carrier type switches from n- to p-type and yield hole mobilities up to 0.45 cm(2) s(-1) with hole to electron mobility ratio of three (mu(h)/mu(e), similar to 3), which indicates that the hole density in the active layer can be significantly increased by exposure to air. This increase is consistent with the intrinsic more delocalized nature of the highest occupied molecular orbital of the charged vinylene polymer, as estimated by density functional theory (DFT) calculations, which facilitates hole transport within the polymer chains. This is the first demonstration of an efficient NDI-based hole semiconducting polymer, which will enable new developments in all-polymer solar cells, complementary circuits, and dopable polymers for use in thermoelectrics.

Linker length dependent binding of a focal adhesion kinase derived peptide to the Src SH3-SH2 domains.

Science.gov (United States)

Lindfors, Hanna E; Venkata, Bharat Somireddy; Drijfhout, Jan W; Ubbink, Marcellus

2011-02-18

The interaction between a peptide encompassing the SH3 and SH2 binding motifs of focal adhesion kinase (FAK) and the Src SH3-SH2 domains has been investigated with NMR spectroscopy and calorimetry. The binding to both motifs is anti-cooperative. Reduction of the long linker connecting the motifs does not lead to cooperativity. Short linkers that do not allow simultaneous intramolecular binding of the peptide to both motifs cause peptide-mediated dimerisation, even with a linker of only three amino acids. The role of the SH3 binding motif is discussed in view of the independent nature of the SH interactions. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Preparation of value-added metal-organic frameworks (MOFs) using waste PET bottles as source of acid linker

CSIR Research Space (South Africa)

Dyosiba, Xoliswa

2016-12-01

Full Text Available of Value-added Metal-organic Frameworks (MOFs) Using Waste PET Bottles as Source of Acid Linker Xoliswa Dyosiba, Jianwei Ren, Nicholas M. Musyoka, Henrietta W. Langmi, Mkhulu Mathe, Maurice S. Onyango PII: S2214-9937(16)30053-7 DOI: doi:10.1016/j..., Hen- rietta W. Langmi, Mkhulu Mathe, Maurice S. Onyango, Preparation of Value-added Metal-organic Frameworks (MOFs) Using Waste PET Bottles as Source of Acid Linker, Sustainable Materials and Technologies (2016), doi:10.1016/j.susmat.2016...

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

CERN Document Server

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

2016-01-01

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.

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

International Nuclear Information System (INIS)

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

2016-01-01

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

A Class of Rigid Linker-bearing Glucosides for Membrane Protein Structural Study

DEFF Research Database (Denmark)

Sadaf, Aiman; Mortensen, Jonas S; Capaldi, Stefano

2016-01-01

with a branched tail group and a triglucoside head group. These head and tail groups were connected via an amide or ether linkage by using a tris(hydroxylmethyl)aminomethane (TRIS) or neopentyl glycol (NPG) linker to produce TRIS-derived triglucosides (TDTs) and NPG-derived triglucosides (NDTs), respectively...

G-CSF receptor-binding cyclic peptides designed with artificial amino-acid linkers

International Nuclear Information System (INIS)

Shibata, Kenji; Maruyama-Takahashi, Kumiko; Yamasaki, Motoo; Hirayama, Noriaki

2006-01-01

Designing small molecules that mimic the receptor-binding local surface structure of large proteins such as cytokines or growth factors is fascinating and challenging. In this study, we designed cyclic peptides that reproduce the receptor-binding loop structures of G-CSF. We found it is important to select a suitable linker to join two or more discontinuous sequences and both termini of the peptide corresponding to the receptor-binding loop. Structural simulations based on the crystallographic structure of KW-2228, a stable and potent analog of human G-CSF, led us to choose 4-aminobenzoic acid (Abz) as a part of the linker. A combination of 4-Abz with β-alanine or glycine, and disulfide bridges between cysteins or homocysteins, gave a structure suitable for receptor binding. In this structure, the side-chains of several amino acids important for the interactions with the receptor are protruding from one side of the peptide ring. This artificial peptide showed G-CSF antagonistic activity in a cell proliferation assay

Distribution of linker histone variants during plant cell differentiation in the developmental zones of the maize root, dedifferentiation in callus culture after auxin treatment

Directory of Open Access Journals (Sweden)

ANASTASIOS ALATZAS

2008-01-01

Full Text Available Although several linker histone variants have been studied in both animal and plant organisms, little is known about their distribution during processes that involve alterations in chromatin function, such as differentiation, dedifferentiation and hormone treatment. In this study, we identified linker histone variants by using specific anti-histone Hl antibodies. Each variant's ratio to total Hl in the three developmental zones of maize (Zea mays L. root and in callus cultures derived from them was estimated in order to define possible alterations either during plant cell differentiation or during their dedifferentiation. We also evaluated linker histone variants' ratios in the developmental zones of maize roots treated with auxin in order to examine the effects of exogenous applied auxin to linker histone variant distribution. Finally, immunohistochemical detection was used to identify the root tissues containing each variant and correlate them with the physiological status of the plant cells. According to the results presented in this study, linker histone variants' ratios are altered in the developmental zones of maize root, while they are similar to the meristematic zone in samples from callus cultures and to the differentiation zone in samples from roots treated with auxin. We propose that the alterations in linker histone variants' ratios are correlated with plant cell differentiation and dedifferentiation.

Substructure of Highly Boosted Massive Jets

Energy Technology Data Exchange (ETDEWEB)

Alon, Raz [Weizmann Inst. of Science, Rehovot (Israel)

2012-10-01

Modern particle accelerators enable researchers to study new high energy frontiers which have never been explored before. This realm opens possibilities to further examine known fields such as Quantum Chromodynamics. In addition, it allows searching for new physics and setting new limits on the existence of such. This study examined the substructure of highly boosted massive jets measured by the CDF II detector. Events from 1.96 TeV proton-antiproton collisions at the Fermilab Tevatron Collider were collected out of a total integrated luminosity of 5.95 fb$^{-1}$. They were selected to have at least one jet with transverse momentum above 400 GeV/c. The jet mass, angularity, and planar flow were measured and compared with predictions of perturbative Quantum Chromodynamics, and were found to be consistent with the theory. A search for boosted top quarks was conducted and resulted in an upper limit on the production cross section of such top quarks.

Studying a denition for a boosted W/Z/H jet tagger at the FCChh, employing modern Machine Learning algorithms and customised features (beyond the usual substructure variables)

CERN Document Server

Brzhechko, Danyyl

2016-01-01

A jet is a spray of particles, usually produced by the hadronization of a quark or gluon in a particle physics or heavy ion experiment. Reconstructed particles are clustered into jets using one of the available jet clustering algorithms (kT, anti-kT etc.), which adopt dierent metrics to decide if two given particles belong to the same jet or not. Jets can also originate from the decay of high-momenta heavy particles, such as boosted vector boson. When these particles decay to quarks, the overlap of the hadronization products of each quark result into a single massive jet, dierent than the ordinary jets from quarks and gluons. These special jets can be identied using substructure algorithms. In this study, we consider the performances of a commonly used substructure variable, N-subjettiness, with two variants of an alternative approach, based on the momentum ow around the jet axis. I focused on high-energy collision in a hypothetical future circular collider (FCC) colliding protons at a center-of-mass energy 1...

SEVA Linkers: A Versatile and Automatable DNA Backbone Exchange Standard for Synthetic Biology

DEFF Research Database (Denmark)

Kim, Se Hyeuk; Cavaleiro, Mafalda; Rennig, Maja

2016-01-01

flexibility, and different researchers prefer and master different molecular technologies. Here, we describe a new, highly versatile and automatable standard “SEVA linkers” for vector exchange. SEVA linkers enable backbone swapping with 20 combinations of classical enzymatic restriction/ligation, Gibson...

Construction of Multivalent Homo- and Heterofunctional ABO Blood Group Glycoconjugates Using a Trifunctional Linker Strategy.

Science.gov (United States)

Daskhan, Gour Chand; Tran, Hanh-Thuc Ton; Meloncelli, Peter J; Lowary, Todd L; West, Lori J; Cairo, Christopher W

2018-02-21

The design and synthesis of multivalent ligands displaying complex oligosaccharides is necessary for the development of therapeutics, diagnostics, and research tools. Here, we report an efficient conjugation strategy to prepare complex glycoconjugates with 4 copies of 1 or 2 separate glycan epitopes, providing 4-8 carbohydrate residues on a tetravalent poly(ethylene glycol) scaffold. This strategy provides complex glycoconjugates that approach the size of glycoproteins (15-18 kDa) while remaining well-defined. The synthetic strategy makes use of three orthogonal functional groups, including a reactive N-hydroxysuccinimide (NHS)-ester moiety on the linker to install the first carbohydrate epitope via reaction with an amine. A masked amine functionality on the linker is revealed after the removal of a fluorenylmethyloxycarbonyl (Fmoc)-protecting group, allowing the attachment to the NHS-activated poly(ethylene glycol) (PEG) scaffold. An azide group in the linker was then used to incorporate the second carbohydrate epitope via catalyzed alkyne-azide cycloaddition. Using a known tetravalent PEG scaffold (PDI, 1.025), we prepared homofunctional glycoconjugates that display four copies of lactose and the A-type II or the B-type II human blood group antigens. Using our trifunctional linker, we expanded this strategy to produce heterofunctional conjugates with four copies of two separate glycan epitopes. These heterofunctional conjugates included Neu5Ac, 3'-sialyllactose, or 6'-sialyllactose as a second antigen. Using an alternative strategy, we generated heterofunctional conjugates with three copies of the glycan epitope and one fluorescent group (on average) using a sequential dual-amine coupling strategy. These conjugation strategies should be easily generalized for conjugation of other complex glycans. We demonstrate that the glycan epitopes of heterofunctional conjugates engage and cluster target B-cell receptors and CD22 receptors on B cells, supporting the

Prescreening of Nicotine Hapten Linkers in Vitro To Select Hapten-Conjugate Vaccine Candidates for Pharmacokinetic Evaluation in Vivo.

Science.gov (United States)

Arutla, Viswanath; Leal, Joseph; Liu, Xiaowei; Sokalingam, Sriram; Raleigh, Michael; Adaralegbe, Adejimi; Liu, Li; Pentel, Paul R; Hecht, Sidney M; Chang, Yung

2017-05-08

Since the demonstration of nicotine vaccines as a possible therapeutic intervention for the effects of tobacco smoke, extensive effort has been made to enhance nicotine specific immunity. Linker modifications of nicotine haptens have been a focal point for improving the immunogenicity of nicotine, in which the evaluation of these modifications usually relies on in vivo animal models, such as mice, rats or nonhuman primates. Here, we present two in vitro screening strategies to estimate and predict the immunogenic potential of our newly designed nicotine haptens. One utilizes a competition enzyme-linked immunoabsorbent assay (ELISA) to profile the interactions of nicotine haptens or hapten-protein conjugates with nicotine specific antibodies, both polyclonal and monoclonal. Another relies on computational modeling of the interactions between haptens and amino acid residues near the conjugation site of the carrier protein to infer linker-carrier protein conjugation effect on antinicotine antibody response. Using these two in vitro methods, we ranked the haptens with different linkers for their potential as viable vaccine candidates. The ELISA-based hapten ranking was in an agreement with the results obtained by in vivo nicotine pharmacokinetic analysis. A correlation was found between the average binding affinity (IC 50 ) of the haptens to an anti-Nic monoclonal antibody and the average brain nicotine concentration in the immunized mice. The computational modeling of hapten and carrier protein interactions helps exclude conjugates with strong linker-carrier conjugation effects and low in vivo efficacy. The simplicity of these in vitro screening strategies should facilitate the selection and development of more effective nicotine conjugate vaccines. In addition, these data highlight a previously under-appreciated contribution of linkers and hapten-protein conjugations to conjugate vaccine immunogenicity by virtue of their inclusion in the epitope that binds and

Substructure analysis techniques and automation. [to eliminate logistical data handling and generation chores

Science.gov (United States)

Hennrich, C. W.; Konrath, E. J., Jr.

1973-01-01

A basic automated substructure analysis capability for NASTRAN is presented which eliminates most of the logistical data handling and generation chores that are currently associated with the method. Rigid formats are proposed which will accomplish this using three new modules, all of which can be added to level 16 with a relatively small effort.

Lensing substructure quantification in RXJ1131-1231: a 2 keV lower bound on dark matter thermal relic mass

Energy Technology Data Exchange (ETDEWEB)

Birrer, Simon; Amara, Adam; Refregier, Alexandre, E-mail: simon.birrer@phys.ethz.ch, E-mail: adam.amara@phys.ethz.ch, E-mail: alexandre.refregier@phys.ethz.ch [Institute for Astronomy, Department of Physics, ETH Zurich, Wolfgang-Pauli-Strasse 27, 8093, Zurich (Switzerland)

2017-05-01

We study the substructure content of the strong gravitational lens RXJ1131-1231 through a forward modelling approach that relies on generating an extensive suite of realistic simulations. We use a semi-analytic merger tree prescription that allows us to stochastically generate substructure populations whose properties depend on the dark matter particle mass. These synthetic halos are then used as lenses to produce realistic mock images that have the same features, e.g. luminous arcs, quasar positions, instrumental noise and PSF, as the data. We then analyse the data and the simulations in the same way with summary statistics that are sensitive to the signal being targeted and are able to constrain models of dark matter statistically using Approximate Bayesian Computing (ABC) techniques. (In this work, we focus on the thermal relic mass estimate and fix the semi-analytic descriptions of the substructure evolution based on recent literature.) We are able, based on the HST data for RXJ1131-1231, to rule out a warm dark matter thermal relic mass below 2 keV at the 2σ confidence level.

THE BOLOCAM GALACTIC PLANE SURVEY. XI. TEMPERATURES AND SUBSTRUCTURE OF GALACTIC CLUMPS BASED ON 350 μM OBSERVATIONS

Energy Technology Data Exchange (ETDEWEB)

Merello, Manuel; Evans II, Neal J. [The University of Texas at Austin, Department of Astronomy, 2515 Speedway, Stop C1400, Austin, TX 78712-1205 (United States); Shirley, Yancy L. [Steward Observatory, University of Arizona, 933 North Cherry Avenue, Tucson, AZ 85721 (United States); Rosolowsky, Erik [Department of Physics, 4-181 CCIS, University of Alberta, Edmonton, AB T6G 2E1 (Canada); Ginsburg, Adam [European Southern Observatory, ESO Headquarters, Karl-Schwarzschild-Strasse 2, D-95748 Garching bei Munchen (Germany); Bally, John [CASA, University of Colorado, 389-UCB, Boulder, CO 80309 (United States); Battersby, Cara; Dunham, Michael M., E-mail: manuel@astro.as.utexas.edu [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, MS 78, Cambridge, MA 02138 (United States)

2015-05-15

We present 107 maps of continuum emission at 350 μm from Galactic molecular clumps. Observed sources were mainly selected from the Bolocam Galactic Plane Survey (BGPS) catalog, with three additional maps covering star-forming regions in the outer Galaxy. The higher resolution of the SHARC-II images (8.″5 beam) compared with the 1.1 mm images from BGPS (33″ beam) allowed us to identify a large population of smaller substructures within the clumps. A catalog is presented for the 1386 sources extracted from the 350 μm maps. The color temperature distribution of clumps based on the two wavelengths has a median of 13.3 K and mean of 16.3 ± 0.4 K, assuming an opacity law index of 1.7. For the structures with good determination of color temperatures, the mean ratio of gas temperature, determined from NH{sub 3} observations, to dust color temperature is 0.88 and the median ratio is 0.76. About half the clumps have more than 2 substructures and 22 clumps have more than 10. The fraction of the mass in dense substructures seen at 350 μm compared to the mass of their parental clump is ∼0.19, and the surface densities of these substructures are, on average, 2.2 times those seen in the clumps identified at 1.1 mm. For a well-characterized sample, 88 structures (31%) exceed a surface density of 0.2 g cm{sup −2}, and 18 (6%) exceed 1.0 g cm{sup −2}, thresholds for massive star formation suggested by theorists.

On jet substructure methods for signal jets

Energy Technology Data Exchange (ETDEWEB)

Dasgupta, Mrinal [Consortium for Fundamental Physics, School of Physics & Astronomy, University of Manchester,Oxford Road, Manchester M13 9PL (United Kingdom); Powling, Alexander [School of Physics & Astronomy, University of Manchester,Oxford Road, Manchester M13 9PL (United Kingdom); Siodmok, Andrzej [Institute of Nuclear Physics, Polish Academy of Sciences,ul. Radzikowskiego 152, 31-342 Kraków (Poland); CERN, PH-TH,CH-1211 Geneva 23 (Switzerland)

2015-08-17

We carry out simple analytical calculations and Monte Carlo studies to better understand the impact of QCD radiation on some well-known jet substructure methods for jets arising from the decay of boosted Higgs bosons. Understanding differences between taggers for these signal jets assumes particular significance in situations where they perform similarly on QCD background jets. As an explicit example of this we compare the Y-splitter method to the more recently proposed Y-pruning technique. We demonstrate how the insight we gain can be used to significantly improve the performance of Y-splitter by combining it with trimming and show that this combination outperforms the other taggers studied here, at high p{sub T}. We also make analytical estimates for optimal parameter values, for a range of methods and compare to results from Monte Carlo studies.

The Effects of Anchor Groups on (1) TiO2-Catalyzed Photooxidation and (2) Linker-Assisted Assembly on TiO2

Science.gov (United States)

Anderson, Ian Mark

Quantum dot-sensitized solar cells (QDSSCs) are a popular target for research due to their potential for highly efficient, easily tuned absorption. Typically, light is absorbed by quantum dots attached to a semiconductor substrate, such as TiO2, via bifunctional linker molecules. This research aims to create a patterned monolayer of linker molecules on a TiO2 film, which would in turn allow the attachment of a patterned layer of quantum dots. One method for the creation of a patterned monolayer is the functionalization of a TiO2 film with a linker molecule, followed by illumination with a laser at 355 nm. This initiates a TiO 2-catalyzed oxidation reaction, causing loss of surface coverage. A second linker molecule can then be adsorbed onto the TiO2 surface in the illuminated area. Towards that end, the behaviors of carboxylic and phosphonic acids adsorbed on TiO2 have been studied. TiO2 films were functionalized by immersion in solutions a single adsorbate and surface coverage was determined by IR spectroscopy. It is shown that phosphonic acids attain higher surface coverage than carboxylic acids, and will displace them from TiO2 when in a polar solvent. Alkyl chain lengths, which can influence stabilities of monolayers, are shown not to have an effect on this relationship. Equilibrium binding data for the adsorption of n-hexadecanoic acid to TiO2 from a THF solution are presented. It is shown that solvent polarity can affect monolayer stability; carboxylates and phosphonates undergo more desorption into polar solvents than nonpolar. Through illumination, it was possible to remove nearly all adsorbed linkers from TiO2. However, the illuminated areas were found not to be receptive to attachment by a second adsorbate. A possible reason for this behavior is presented. I also report on the synthesis and characterization of a straight-chain, thiol-terminated phosphonic acid. Initial experiments involving monolayer formation and quantum dot attachment are presented

The specificity of Av3 sea anemone toxin for arthropods is determined at linker DI/SS2-S6 in the pore module of target sodium channels.

Science.gov (United States)

Gur Barzilai, Maya; Kahn, Roy; Regev, Noa; Gordon, Dalia; Moran, Yehu; Gurevitz, Michael

2014-10-15

Av3 is a peptide neurotoxin from the sea anemone Anemonia viridis that shows specificity for arthropod voltage-gated sodium channels (Navs). Interestingly, Av3 competes with a scorpion α-toxin on binding to insect Navs and similarly inhibits the inactivation process, and thus has been classified as 'receptor site-3 toxin', although the two peptides are structurally unrelated. This raises questions as to commonalities and differences in the way both toxins interact with Navs. Recently, site-3 was partly resolved for scorpion α-toxins highlighting S1-S2 and S3-S4 external linkers at the DIV voltage-sensor module and the juxtaposed external linkers at the DI pore module. To uncover channel determinants involved in Av3 specificity for arthropods, the toxin was examined on channel chimaeras constructed with the external linkers of the mammalian brain Nav1.2a, which is insensitive to Av3, in the background of the Drosophila DmNav1. This approach highlighted the role of linker DI/SS2-S6, adjacent to the channel pore, in determining Av3 specificity. Point mutagenesis at DI/SS2-S6 accompanied by functional assays highlighted Trp404 and His405 as a putative point of Av3 interaction with DmNav1. His405 conservation in arthropod Navs compared with tyrosine in vertebrate Navs may represent an ancient substitution that explains the contemporary selectivity of Av3. Trp404 and His405 localization near the membrane surface and the hydrophobic bioactive surface of Av3 suggest that the toxin possibly binds at a cleft by DI/S6. A partial overlap in receptor site-3 of both toxins nearby DI/S6 may explain their binding competition capabilities.

Inverse Effects on Gating and Modulation Caused by a Mutation in the M2-M3 Linker of the GABAA Receptor γ SubunitS⃞

OpenAIRE

O'Shea, Sean M.; Williams, Carrie A.; Jenkins, Andrew

2009-01-01

M2-M3 linkers are receptor subunit domains known to be critical for the normal function of cysteine-loop ligand-gated ion channels. Previous studies of α and β subunits of type “A” GABA receptors suggest that these linkers couple extracellular elements involved in GABA binding to the transmembrane segments that control the opening of the ion channel. To study the importance of the γ subunit M2-M3 linker, we examined the macroscopic and single-channel effects of an engi...

Novel cross-linkers for PDMS networks for controlled and well distributed grafting of functionalities by click chemistry

DEFF Research Database (Denmark)

Bahrt, Frederikke; Dimitrov, Ivaylo; Daugaard, Anders Egede

2013-01-01

by 35%. The contact angle of PDMS films was increased from 108° to 116° by the introduction of a small poly(pentafluorostyrene) chain. Finally, 17α-ethynyl-1,3,5(10)-estratriene-3,17β-diol and 1-ethynyl-3,5- bis(trifluoromethyl)benzene were incorporated as examples of other functional groups. © 2013......-linkers have been utilized to prepare novel polydimethylsiloxane (PDMS) networks. All functional cross-linkers were successfully incorporated into the networks and were demonstrated to be well distributed within the PDMS films. This was substantiated by fluorescence microscopy of a film prepared with the 4...

Destabilization of the Outer and Inner Mitochondrial Membranes by Core and Linker Histones

Science.gov (United States)

Cascone, Annunziata; Bruelle, Celine; Lindholm, Dan; Bernardi, Paolo; Eriksson, Ove

2012-01-01

Background Extensive DNA damage leads to apoptosis. Histones play a central role in DNA damage sensing and may mediate signals of genotoxic damage to cytosolic effectors including mitochondria. Methodology/Principal Findings We have investigated the effects of histones on mitochondrial function and membrane integrity. We demonstrate that both linker histone H1 and core histones H2A, H2B, H3, and H4 bind strongly to isolated mitochondria. All histones caused a rapid and massive release of the pro-apoptotic intermembrane space proteins cytochrome c and Smac/Diablo, indicating that they permeabilize the outer mitochondrial membrane. In addition, linker histone H1, but not core histones, permeabilized the inner membrane with a collapse of the membrane potential, release of pyridine nucleotides, and mitochondrial fragmentation. Conclusions We conclude that histones destabilize the mitochondrial membranes, a mechanism that may convey genotoxic signals to mitochondria and promote apoptosis following DNA damage. PMID:22523586

Computational engineering of cellulase Cel9A-68 functional motions through mutations in its linker region.

Science.gov (United States)

Costa, M G S; Silva, Y F; Batista, P R

2018-03-14

Microbial cellulosic degradation by cellulases has become a complementary approach for biofuel production. However, its efficiency is hindered by the recalcitrance of cellulose fibres. In this context, computational protein design methods may offer an efficient way to obtain variants with improved enzymatic activity. Cel9A-68 is a cellulase from Thermobifida fusca that is still active at high temperatures. In a previous work, we described a collective bending motion, which governs the overall cellulase dynamics. This movement promotes the approximation of its CBM and CD structural domains (that are connected by a flexible linker). We have identified two residues (G460 and P461) located at the linker that act as a hinge point. Herein, we applied a new level of protein design, focusing on the modulation of this collective motion to obtain cellulase variants with enhanced functional dynamics. We probed whether specific linker mutations would affect Cel9A-68 dynamics through computational simulations. We assumed that P461G and G460+ (with an extra glycine) constructs would present enhanced interdomain motions, while the G460P mutant would be rigid. From our results, the P461G mutation resulted in a broader exploration of the conformational space, as confirmed by clustering and free energy analyses. The WT enzyme was the most rigid system. However, G460P and P460+ explored distinct conformational states described by opposite directions of low-frequency normal modes; they sampled preferentially closed and open conformations, respectively. Overall, we highlight two significant findings: (i) all mutants explored larger conformational spaces than the WT; (ii) the selection of distinct conformational populations was intimately associated with the mutation considered. Thus, the engineering of Cel9A-68 motions through linker mutations may constitute an efficient way to improve cellulase activity, facilitating the disruption of cellulose fibres.

Modulation of procaspase-7 self-activation by PEST amino acid residues of the N-terminal prodomain and intersubunit linker.

Science.gov (United States)

Alves, Juliano; Garay-Malpartida, Miguel; Occhiucci, João M; Belizário, José E

2017-12-01

Procaspase-7 zymogen polypeptide is composed of a short prodomain, a large subunit (p20), and a small subunit (p10) connected to an intersubunit linker. Caspase-7 is activated by an initiator caspase-8 and -9, or by autocatalysis after specific cleavage at IQAD 198 ↓S located at the intersubunit linker. Previously, we identified that PEST regions made of amino acid residues Pro (P), Glu (E), Asp (D), Ser (S), Thr (T), Asn (N), and Gln (Q) are conserved flanking amino acid residues in the cleavage sites within a prodomain and intersubunit linker of all caspase family members. Here we tested the impact of alanine substitution of PEST amino acid residues on procaspase-7 proteolytic self-activation directly in Escherichia coli. The p20 and p10 subunit cleavage were significantly delayed in double caspase-7 mutants in the prodomain (N18A/P26A) and intersubunit linker (S199A/P201A), compared with the wild-type caspase-7. The S199A/P201A mutants effectively inhibited the p10 small subunit cleavage. However, the mutations did not change the kinetic parameters (k cat /K M ) and optimal tetrapeptide specificity (DEVD) of the purified mutant enzymes. The results suggest a role of PEST-amino acid residues in the molecular mechanism for prodomain and intersubunit cleavage and caspase-7 self-activation.

Synthesis of highly fluorescent and thio-linkers stabilize gold quantum dots and nano clusters in DMF for bio-labeling

Energy Technology Data Exchange (ETDEWEB)

Rastogi, Shiva K., E-mail: srastogi@uidaho.edu [University of Idaho, Department of Chemistry (United States); Denn, Benjamin D.; Branen, A. Larry [University of Idaho, Coeur D' Alene, Biosensors and Nanotechnology Application Laboratory (BNAL) (United States)

2012-01-15

This study demonstrates a one versus two-step synthesis of fluorescent gold quantum dots (F-AuQDs) and nano clusters (F-AuNCs) functionalized with thiolated organic linkers using reduction of gold precursor in N,N Prime -dimethylformamide in 1 h of reaction. The F-AuQDs and F-AuNCs show fluorescence emission at 425 {+-} 5 nm upon excitation at 345 {+-} 5 nm of wavelength, with good water solubility and stability. Five different thiolated organic binary linkers consisting of various functional groups including: carboxylic acid, hydroxyl, and aromatic amine, were conjugated with the F-AuQDs and F-AuNCs. The formation mechanism and functionalization of the F-AuQDs and F-AuNCs was characterized using UV-vis absorption spectra, UV-vis light, fluorescent emission spectra, pH, TEM, and FTIR. The fluorescence emission of the F-AuQDs and F-AuNCs is greatly dependent on the thio-linker. This novel one-step approach provides facile and fast synthesis of F-AuQDs and F-AuNCs over the two-step method, with less than 5 h of reaction and workup compared to more than 28 h of reaction for the two-step approach. These thio-linker functionalized F-AuQDs and F-AuNCs have a wide application in fluorescent labeling of biomolecules, optical devices, imaging, energy transfer, and biosensing.

Correlation between the sub-structure parameters and the manufacturing technologies of metal threads in historical textiles using X-ray line profile analysis

Energy Technology Data Exchange (ETDEWEB)

Csiszar, Gabor; Ungar, Tamas [Eoetvoes University Budapest, Department of Materials Physics, Budapest (Hungary); Jaro, Marta [Hungarian National Museum, Budapest (Hungary)

2013-06-15

Micro-structure can talk when documentation is missing. In ancient Roman or medieval periods, kings, queens, or just rich people decorated their clothes or even their horse covers richly with miniature jewels or metal threads. The origin or the fabrication techniques of these ancient threads is often unknown. Thirteen thread samples made of gold or gilt silver manufactured during the last sixteen hundred years are investigated for the micro-structure in terms of dislocation density, crystallite size, and planar defects. In a few cases, these features are compared with sub-structure of similar metallic threads prepared in modern, twentieth century workshops. The sub-structure is determined by X-ray line profile analysis, using high resolution diffractograms with negligible instrumental broadening. On the basis of the sub-structure parameters, we attempt to assess the metal-threads manufacturing procedures on samples stemming from the fourth century A.D. until now. (orig.)

Differential solvation of intrinsically disordered linkers drives the formation of spatially organized droplets in ternary systems of linear multivalent proteins

Science.gov (United States)

Harmon, Tyler S.; Holehouse, Alex S.; Pappu, Rohit V.

2018-04-01

Intracellular biomolecular condensates are membraneless organelles that encompass large numbers of multivalent protein and nucleic acid molecules. The bodies assemble via a combination of liquid–liquid phase separation and gelation. A majority of condensates included multiple components and show multilayered organization as opposed to being well-mixed unitary liquids. Here, we put forward a simple thermodynamic framework to describe the emergence of spatially organized droplets in multicomponent systems comprising of linear multivalent polymers also known as associative polymers. These polymers, which mimic proteins and/or RNA have the architecture of domains or motifs known as stickers that are interspersed by flexible spacers known as linkers. Using a minimalist numerical model for a four-component system, we have identified features of linear multivalent molecules that are necessary and sufficient for generating spatially organized droplets. We show that differences in sequence-specific effective solvation volumes of disordered linkers between interaction domains enable the formation of spatially organized droplets. Molecules with linkers that are preferentially solvated are driven to the interface with the bulk solvent, whereas molecules that have linkers with negligible effective solvation volumes form cores in the core–shell architectures that emerge in the minimalist four-component systems. Our modeling has relevance for understanding the physical determinants of spatially organized membraneless organelles.

Precast concrete elements for accelerated bridge construction : laboratory testing of precast substructure components, Boone County bridge.

Science.gov (United States)

2009-01-01

Vol. 1-1: In July 2006, construction began on an accelerated bridge project in Boone County, Iowa that was composed of precast substructure : elements and an innovative, precast deck panel system. The superstructure system consisted of full-depth dec...

Convergence properties of halo merger trees; halo and substructure merger rates across cosmic history

Science.gov (United States)

Poole, Gregory B.; Mutch, Simon J.; Croton, Darren J.; Wyithe, Stuart

2017-12-01

We introduce GBPTREES: an algorithm for constructing merger trees from cosmological simulations, designed to identify and correct for pathological cases introduced by errors or ambiguities in the halo finding process. GBPTREES is built upon a halo matching method utilizing pseudo-radial moments constructed from radially sorted particle ID lists (no other information is required) and a scheme for classifying merger tree pathologies from networks of matches made to-and-from haloes across snapshots ranging forward-and-backward in time. Focusing on SUBFIND catalogues for this work, a sweep of parameters influencing our merger tree construction yields the optimal snapshot cadence and scanning range required for converged results. Pathologies proliferate when snapshots are spaced by ≲0.128 dynamical times; conveniently similar to that needed for convergence of semi-analytical modelling, as established by Benson et al. Total merger counts are converged at the level of ∼5 per cent for friends-of-friends (FoF) haloes of size np ≳ 75 across a factor of 512 in mass resolution, but substructure rates converge more slowly with mass resolution, reaching convergence of ∼10 per cent for np ≳ 100 and particle mass mp ≲ 109 M⊙. We present analytic fits to FoF and substructure merger rates across nearly all observed galactic history (z ≤ 8.5). While we find good agreement with the results presented by Fakhouri et al. for FoF haloes, a slightly flatter dependence on merger ratio and increased major merger rates are found, reducing previously reported discrepancies with extended Press-Schechter estimates. When appropriately defined, substructure merger rates show a similar mass ratio dependence as FoF rates, but with stronger mass and redshift dependencies for their normalization.

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

Directory of Open Access Journals (Sweden)

Saurabh Chaturvedi

2017-01-01

Full Text Available 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.

Substructure hybrid testing of reinforced concrete shear wall structure using a domain overlapping technique

Science.gov (United States)

Zhang, Yu; Pan, Peng; Gong, Runhua; Wang, Tao; Xue, Weichen

2017-10-01

An online hybrid test was carried out on a 40-story 120-m high concrete shear wall structure. The structure was divided into two substructures whereby a physical model of the bottom three stories was tested in the laboratory and the upper 37 stories were simulated numerically using ABAQUS. An overlapping domain method was employed for the bottom three stories to ensure the validity of the boundary conditions of the superstructure. Mixed control was adopted in the test. Displacement control was used to apply the horizontal displacement, while two controlled force actuators were applied to simulate the overturning moment, which is very large and cannot be ignored in the substructure hybrid test of high-rise buildings. A series of tests with earthquake sources of sequentially increasing intensities were carried out. The test results indicate that the proposed hybrid test method is a solution to reproduce the seismic response of high-rise concrete shear wall buildings. The seismic performance of the tested precast high-rise building satisfies the requirements of the Chinese seismic design code.

Substructural evolution during cyclic torsion of drawn low carbon steel bars

International Nuclear Information System (INIS)

Correa, E.C.S.; Aguilar, M.T.P.; Monteiro, W.A.; Cetlin, P.R.

2006-01-01

Strain softening effects have been previously observed in drawn low carbon steel bars as a result of cyclic torsion experiments. In this paper, the substructural aspects related to the phenomenon have been investigated. Single pass drawn bars were subjected to a quarter, to a half, to a full torsion cycle and to 10 such cycles. Transmission electron microscopy revealed the development of extended microbands crossing the former dislocation arrangement of the drawn metal, which evolves to a rectangular shaped subgrains structure as torsion deformation is conducted

Low Density Lipoprotein Receptor Class A Repeats Are O-Glycosylated in Linker Regions

DEFF Research Database (Denmark)

Pedersen, Nis Borbye; Wang, Shengjun; Narimatsu, Yoshiki

2014-01-01

, which in wild-type CHO cells is glycosylated with the typical sialylated core 1 structure. The glycosites in linker regions of LDLR class A repeats are conserved in LDLR from man to Xenopus and found in other homologous receptors. O-Glycosylation is controlled by a large family of polypeptide Gal...

Substitution of the Lys linker with the β-Ala linker dramatically decreased the renal uptake of 99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone peptides.

Science.gov (United States)

Flook, Adam M; Yang, Jianquan; Miao, Yubin

2014-11-13

The purpose of this study was to examine whether the substitution of the Lys linker with the β-Ala could reduce the renal uptake of (99m)Tc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-β-Ala-(Arg(11))CCMSH (1) {c[Arg-Ser-Asp-dTyr-Asp]-β-Ala-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RTD-β-Ala-(Arg(11))CCMSH (2), RVD-β-Ala-(Arg(11))CCMSH (3), RAD-β-Ala-(Arg(11))CCMSH (4), NAD-β-Ala-(Arg(11))CCMSH (5), and EAD-β-Ala-(Arg(11))CCMSH (6) peptides were synthesized and evaluated for their melanocortin 1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of their (99m)Tc-conjugates were determined in B16/F1 melanoma-bearing C57 mice. The substitution of the Lys linker with β-Ala linker dramatically reduced the renal uptake of all six (99m)Tc-peptides. (99m)Tc-4 exhibited the highest melanoma uptake (15.66 ± 6.19% ID/g) and the lowest kidney uptake (20.18 ± 3.86% ID/g) among these (99m)Tc-peptides at 2 h postinjection. The B16/F1 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using (99m)Tc-4 as an imaging probe.

Influence of solidification parameters on the cellular sub-structure of tin and some tin alloys; Uticaj nekih parametara ocvrscavanja na celularnu substrukturu kalaja i nekih njegovih legura

Energy Technology Data Exchange (ETDEWEB)

Milosavljevic, Dj [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Yugoslavia)

1965-11-15

This paper describes an attempt to obtain qualitative data on sub-structure of samples solidified in contact with the cooler. The objective of experiments was to study micro segregation phenomena by investigating the substructure in the solidified sample obtained under experimental conditions which are similar to real solidification conditions.

Distribution of distances between dislocations in different types of dislocation substructures in deformed Cu-Al alloys

Energy Technology Data Exchange (ETDEWEB)

Trishkina, L., E-mail: trishkina.53@mail.ru; Zboykova, N.; Koneva, N., E-mail: koneva@tsuab.ru; Kozlov, E. [Tomsk State University of Architecture and Building, 2 Solyanaya St., Tomsk, 634003 (Russian Federation); Cherkasova, T. [Tomsk State University of Architecture and Building, 2 Solyanaya St., Tomsk, 634003 (Russian Federation); National Research Tomsk Polytechnic University, 50 Lenin Ave., Tomsk, 634050 (Russian Federation)

2016-01-15

The aim of the investigation was the determination of the statistic description of dislocation distribution in each dislocation substructures component forming after different deformation degrees in the Cu-Al alloys. The dislocation structures were investigated by the transmission diffraction electron microscopy method. In the work the statistic description of distance distribution between the dislocations, dislocation barriers and dislocation tangles in the deformed Cu-Al alloys with different concentration of Al and test temperature at the grain size of 100 µm was carried out. It was established that the above parameters influence the dislocation distribution in different types of the dislocation substructures (DSS): dislocation chaos, dislocation networks without disorientation, nondisoriented and disoriented cells, in the walls and inside the cells. The distributions of the distances between dislocations in the investigated alloys for each DSS type formed at certain deformation degrees and various test temperatures were plotted.

Distribution of distances between dislocations in different types of dislocation substructures in deformed Cu-Al alloys

Science.gov (United States)

Trishkina, L.; Cherkasova, T.; Zboykova, N.; Koneva, N.; Kozlov, E.

2016-01-01

The aim of the investigation was the determination of the statistic description of dislocation distribution in each dislocation substructures component forming after different deformation degrees in the Cu-Al alloys. The dislocation structures were investigated by the transmission diffraction electron microscopy method. In the work the statistic description of distance distribution between the dislocations, dislocation barriers and dislocation tangles in the deformed Cu-Al alloys with different concentration of Al and test temperature at the grain size of 100 µm was carried out. It was established that the above parameters influence the dislocation distribution in different types of the dislocation substructures (DSS): dislocation chaos, dislocation networks without disorientation, nondisoriented and disoriented cells, in the walls and inside the cells. The distributions of the distances between dislocations in the investigated alloys for each DSS type formed at certain deformation degrees and various test temperatures were plotted.

Chemical composition of stars in kinematical substructures of the galactic disk

Directory of Open Access Journals (Sweden)

Gorbaneva T.I.

2012-02-01

Full Text Available The Y, Zr, La, Ce, Nd , Sm and Eu abundances were found in LTE approach, and the abundance of Ba was computed in NLTE approximation for 280 FGK dwarfs in the region of metallicity of − 1<[Fe]< + 0.3. The selection of stars belonging to thin and thick disks and the stream Hercules was made on kinematic criteria. The analysis of enrichment of the different substructures of the Galaxy with α-element (Mg, Si, the iron peak (Ni and neutron-capture elements was carried out.

Preparation and in vivo evaluation of linkers for 211At labeling of humanized anti-Tac

International Nuclear Information System (INIS)

Yordanov, A.T.; Garmestani, K.; Zhang, M.; Zhang, Z.; Yao, Z.; Phillips, K.E.; Herring, B.; Horak, E.; Beitzel, M.P.; Schwarz, U.P.; Gansow, O.A.; Plascjak, P.S.; Eckelman, W.C.; Waldmann, T.A.; Brechbiel, M.W.

2001-01-01

The syntheses, radiolabeling, antibody conjugation, and in vivo evaluation of new linkers for 211 At labeling of humanized anti-Tac (Hu-anti-Tac), an antibody to the α-chain of the IL-2 receptor (IL-2Rα) shown to be a useful target for radioimmunotherapy are described. Synthesis of the organometallic linker precursors is accomplished by reaction of the corresponding bromo- or iodoaryl esters with bis(tributyltin) in the presence of a palladium catalyst. Subsequent conversion to the corresponding N-succinimidyl ester and labeling with 211 At of two new linkers, N-succinimidyl 4-[ 211 At]astato-3-methylbenzoate and N-succinimidyl N-(4-[ 211 At]astatophenethyl)succinamate (SAPS), together with the previously reported N-succinimidyl 4-[ 211 At]astatobenzoate and N-succinimidyl 3-[ 211 At]astato-4-methylbenzoate, are each conjugated to Hu-anti-Tac. The plasma survival times of these conjugates are compared to those of directly iodinated ( 125 I) Hu-anti-Tac. The N-succinimidyl N-(4-[ 211 At]astatophenethyl)succinamate compound (SAPS) emerged from this assay as the most viable candidate for 211 At-labeling of Hu-anti-Tac. SAPS, along with the directly analogous radio-iodinated reagent, N-succinimidyl N-(4-[ 125 I]astatophenethyl)succinamate (SIPS), are evaluated in a biodistribution study along with directly iodinated ( 125 I) Hu-anti-Tac. Blood clearance and biological accretion results indicate that SAPS is a viable candidate for further evaluation for radioimmunotherapy of cancer

Doxorubicin conjugation and drug linker chemistry alter the intravenous and pulmonary pharmacokinetics of a PEGylated Generation 4 polylysine dendrimer in rats.

Science.gov (United States)

Leong, Nathania J; Mehta, Dharmini; McLeod, Victoria M; Kelly, Brian D; Pathak, Rashmi; Owen, David J; Porter, Christopher Jh; Kaminskas, Lisa M

2018-05-28

PEGylated polylysine dendrimers have demonstrated potential as inhalable drug delivery systems that can improve the treatment of lung cancers. Their treatment potential may be enhanced by developing constructs that display prolonged lung retention, together with good systemic absorption, the capacity to passively target lung tumours from the blood and highly selective, yet rapid liberation in the tumour microenvironment. This study sought to characterise how the nature of cathepsin B cleavable peptide linkers, used to conjugate doxorubicin to a PEGylated (PEG570) G4 polylysine dendrimer, affect drug liberation kinetics and intravenous and pulmonary pharmacokinetics in rats. The construct bearing a self-emolative diglycolic acid-V-Citrulline linker exhibited faster doxorubicin release kinetics compared to constructs bearing self emolative diglycolic acid-GLFG, or non-self emolative glutaric acid-GLFG linkers. The V-Citrulline construct exhibited slower plasma clearance, but faster absorption from the lungs than a GLFG construct, although mucociliary clearance and urinary elimination were unchanged. Doxorubicin-conjugation enhanced localisation in the bronchoalveolar lavage fluid compared to lung tissue, suggesting that projection of doxorubicin from the dendrimer surface reduced tissue uptake. These data show that the linker chemistry employed to conjugate drugs to PEGylated carriers can affect drug release profiles and systemic and lung disposition. Copyright © 2018. Published by Elsevier Inc.

Observation of the substructure in the electron bunch on the ACO storage ring

International Nuclear Information System (INIS)

Bergher, M.; Velghe, M.; Mialocq, J.P.

1984-09-01

In the future, one interesting point of the SRFEL at Orsay will be the microtemporal analysis of the laser beam correlated with that of the electron bunch. In a first time, we have only analysed the temporal structure of the electron bunch with an Electrophotonic streak camera. The first results seem to indicate that the bunch is not an homogeneous bunch but presents a substructure. We discuss with details this data

Substructuring preconditioners for an h-p domain decomposition method with interior penalty mortaring

KAUST Repository

Antonietti, P. F.; Ayuso Dios, Blanca; Bertoluzza, S.; Pennacchio, M.

2014-01-01

We propose and study an iterative substructuring method for an h-p Nitsche-type discretization, following the original approach introduced in Bramble et al. Math. Comp. 47(175):103–134, (1986) for conforming methods. We prove quasi-optimality with respect to the mesh size and the polynomial degree for the proposed preconditioner. Numerical experiments assess the performance of the preconditioner and verify the theory. © 2014, Springer-Verlag Italia.

Substructuring preconditioners for an h-p domain decomposition method with interior penalty mortaring

KAUST Repository

Antonietti, P. F.

2014-05-13

We propose and study an iterative substructuring method for an h-p Nitsche-type discretization, following the original approach introduced in Bramble et al. Math. Comp. 47(175):103–134, (1986) for conforming methods. We prove quasi-optimality with respect to the mesh size and the polynomial degree for the proposed preconditioner. Numerical experiments assess the performance of the preconditioner and verify the theory. © 2014, Springer-Verlag Italia.

Structural and Functional Analysis of the Signal-Transducing Linker in the pH-Responsive One-Component System CadC of Escherichia coli.

Science.gov (United States)

Buchner, Sophie; Schlundt, Andreas; Lassak, Jürgen; Sattler, Michael; Jung, Kirsten

2015-07-31

The pH-responsive one-component signaling system CadC in Escherichia coli belongs to the family of ToxR-like proteins, whose members share a conserved modular structure, with an N-terminal cytoplasmic winged helix-turn-helix DNA-binding domain being followed by a single transmembrane helix and a C-terminal periplasmic pH-sensing domain. In E. coli CadC, a cytoplasmic linker comprising approximately 50 amino acids is essential for transmission of the signal from the sensor to the DNA-binding domain. However, the mechanism of transduction is poorly understood. Using NMR spectroscopy, we demonstrate here that the linker region is intrinsically disordered in solution. Furthermore, mutational analyses showed that it tolerates a range of amino acid substitutions (altering polarity, rigidity and α-helix-forming propensity), is robust to extension but is sensitive to truncation. Indeed, truncations either reversed the expression profile of the target operon cadBA or decoupled expression from external pH altogether. CadC dimerizes via its periplasmic domain, but light-scattering analysis provided no evidence for dimerization of the isolated DNA-binding domain, with or without the linker region. However, bacterial two-hybrid analysis revealed that CadC forms stable dimers in a stimulus- and linker-dependent manner, interacting only at pHpH. Thus, we propose that the disordered CadC linker is required for transducing the pH-dependent response of the periplasmic sensor into a structural rearrangement that facilitates dimerization of the cytoplasmic CadC DNA-binding domain. Copyright © 2015 Elsevier Ltd. All rights reserved.

What (if anything) can few-body strange systems teach us about quark-gluon hadronic substructure?

International Nuclear Information System (INIS)

Maltman, K.

1990-01-01

We discuss expectation, relevant to the proposed (π,K) program at PILAC, for the effects of hadronic quark-gluon substructure on the physics of few-body strangeness -1 systems, in the context of QCD-inspired models used previously to describe the hadron spectrum and short distance nucleon-nucleon scattering. 50 refs., 2 tabs

Microdistribution of phases and substructure of the composite electrolytic self-lubricating copper-molybdenite coating

International Nuclear Information System (INIS)

Pribysh, I.Z.; Bakakin, G.N.; Borzyak, A.G.; Sajfullin, R.S.

1978-01-01

The influence of MoS 2 particles on the substructure of a copper matrix was studied, and their location in the composition was established. It is shown that the presence of molybdenite causes a variation in the conditions of electrical crystallization of copper. The optimum composition has been found, which is used as a self-lubricating coating for friction machine parts

Decorrelated Jet Substructure Tagging using Adversarial Neural Networks

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CERN. Geneva

2017-01-01

We describe a strategy for constructing a neural network jet substructure tagger which powerfully discriminates boosted decay signals while remaining largely uncorrelated with the jet mass. This reduces the impact of systematic uncertainties in background modeling while enhancing signal purity, resulting in improved discovery significance relative to existing taggers. The network is trained using an adversarial strategy, resulting in a tagger that learns to balance classification accuracy with decorrelation. As a benchmark scenario, we consider the case where large-radius jets originating from a boosted Z' decay are discriminated from a background of nonresonant quark and gluon jets. We show that in the presence of systematic uncertainties on the background rate, our adversarially-trained, decorrelated tagger considerably outperforms a conventionally trained neural network, despite having a slightly worse signal-background separation power. We generalize the adversarial training technique to include a paramet...

Mixed-linker zeolitic imidazolate framework mixed-matrix membranes for aggressive CO2 separation from natural gas

KAUST Repository

Thompson, Joshua A.; Vaughn, Justin T.; Brunelli, Nicholas A.; Koros, William J.; Jones, Christopher W.; Nair, Sankar

2014-01-01

Zeolitic imidazolate framework (ZIF) materials are a promising subclass of metal-organic frameworks (MOF) for gas separations. However, due to the deleterious effects of gate-opening phenomena associated with organic linker rotation near

AFM friction and adhesion mapping of the substructures of human hair cuticles

International Nuclear Information System (INIS)

Smith, James R.; Tsibouklis, John; Nevell, Thomas G.; Breakspear, Steven

2013-01-01

Using atomic force microscopy, values of the microscale friction coefficient, the tip (silicon nitride) - surface adhesion force and the corresponding adhesion energy, for the substructures that constitute the surface of human hair (European brown hair) have been determined from Amonton plots. The values, mapped for comparison with surface topography, corresponded qualitatively with the substructures’ plane surface characteristics. Localised maps and values of the frictional coefficient, extracted avoiding scale edge effects, are likely to inform the formulation of hair-care products and treatments.

Identification of Epithelial-Mesenchymal Transition-related Target Genes Induced by the Mutation of Smad3 Linker Phosphorylation

Science.gov (United States)

Park, Sujin; Yang, Kyung-Min; Park, Yuna; Hong, Eunji; Hong, Chang Pyo; Park, Jinah; Pang, Kyoungwha; Lee, Jihee; Park, Bora; Lee, Siyoung; An, Haein; Kwak, Mi-Kyung; Kim, Junil; Kang, Jin Muk; Kim, Pyunggang; Xiao, Yang; Nie, Guangjun; Ooshima, Akira

2018-01-01

Background Smad3 linker phosphorylation plays essential roles in tumor progression and metastasis. We have previously reported that the mutation of Smad3 linker phosphorylation sites (Smad3-Erk/Pro-directed kinase site mutant constructs [EPSM]) markedly reduced the tumor progression while increasing the lung metastasis in breast cancer. Methods We performed high-throughput RNA-Sequencing of the human prostate cancer cell lines infected with adenoviral Smad3-EPSM to identify the genes regulated by Smad3-EPSM. Results In this study, we identified genes which are differentially regulated in the presence of Smad3-EPSM. We first confirmed that Smad3-EPSM strongly enhanced a capability of cell motility and invasiveness as well as the expression of epithelial-mesenchymal transition marker genes, CDH2, SNAI1, and ZEB1 in response to TGF-β1 in human pancreatic and prostate cancer cell lines. We identified GADD45B, CTGF, and JUNB genes in the expression profiles associated with cell motility and invasiveness induced by the Smad3-EPSM. Conclusions These results suggested that inhibition of Smad3 linker phosphorylation may enhance cell motility and invasiveness by inducing expression of GADD45B, CTGF, and JUNB genes in various cancers. PMID:29629343

Surface expression and subunit specific control of steady protein levels by the Kv7.2 helix A-B linker.

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Paloma Aivar

Full Text Available Kv7.2 and Kv7.3 are the main components of the neuronal voltage-dependent M-current, which is a subthreshold potassium conductance that exerts an important control on neuronal excitability. Despite their predominantly intracellular distribution, these channels must reach the plasma membrane in order to control neuronal activity. Thus, we analyzed the amino acid sequence of Kv7.2 to identify intrinsic signals that may control its surface expression. Removal of the interlinker connecting helix A and helix B of the intracellular C-terminus produces a large increase in the number of functional channels at the plasma membrane. Moreover, elimination of this linker increased the steady-state amount of protein, which was not associated with a decrease of protein degradation. The magnitude of this increase was inversely correlated with the number of helix A - helix B linkers present in the tetrameric channel assemblies. In contrast to the remarkable effect on the amount of Kv7.2 protein, removal of the Kv7.2 linker had no detectable impact on the steady-state levels of Kv7.3 protein.

The nonlinear response of the complex structural system in nuclear reactors using dynamic substructure method

International Nuclear Information System (INIS)

Zheng, Z.C.; Xie, G.; Du, Q.H.

1987-01-01

Because of the existence of nonlinear characteristics in practical engineering structures, such as large steam turbine-foundation system and offshore platform, it is necessary to predict nonlinear dynamic responses for these very large and complex structural systems subjected extreme load. Due to the limited storage and high executing cost of computers, there are still some difficulties in the analysis for such systems although the traditional finite element methods provide basic available methods to the problems. The dynamic substructure methods, which were developed as a branch of general structural dynamics in the past more than 20 years and have been widely used from aircraft, space vehicles to other mechanical and civil engineering structures, present a powerful method to the analysis of very large structural systems. The key to success is due to the considerable reduction in the number of degrees of freedom while not changing the physical essence of the problems investigated. The dynamic substructure method has been extended to nonlinear system and applicated to the analysis of nonlinear dynamic response of an offshore platform by Z.C. Zheng, et al. (1983, 1985a, b, c). In this paper, the method is presented to analyze dynamic responses of the systems contained intrinsic nonlinearities and with nonlinear attachments and nonlinear supports of nuclear structural systems. The efficiency of the method becomes more clear for nonlinear dynamic problems due to the adoption of iterating processes. For simplicity, the analysis procedure is demonstrated briefly. The generalized substructure method of nonlinear systems is similar to linear systems, only the nonlinear terms are treated as pseudo-forces. Interface coordinates are classified into two categories, the connecting interface coordinates which connect with each other directly in the global system and the linking interface coordinates which link to each other through attachments. (orig./GL)

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

Science.gov (United States)

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…

Influence of ausforming on substructures and shape memory behavior in Fe-28Mn-6Si-5Cr alloy

International Nuclear Information System (INIS)

Wang, D.; Ji, W.; Han, M.; Jia, D.; Liu, W.

2000-01-01

The influence of ausforming (deformation of austenite at temperatures above Md) on shape memory effect (SME) and the substructures in Fe-28Mn-6Si-5Cr (wt.%) alloy were studied, intending to reveal the dominating factor for SME in terms of microstructural characteristics in comparison with the case of thermo-mechanical training. It was found that the SME in the studied alloy could be effectively improved by ausforming at 700 C for 9% tensile strain, in the process of which the oriented stacking faults and dislocations were evolved and regularly distributed in austenite. The improvement of SME by ausforming, as well as thermo-mechanical training, is attributed to the restored substructures in austenite; while there is no closely correspondent relation between SME and the strength of austenite matrix. (orig.)

Dynamic Analysis of Jacket Substructure for Offshore Wind Turbine Generators under Extreme Environmental Conditions

Directory of Open Access Journals (Sweden)

Wen-Jeng Lai

2016-10-01

Full Text Available In order to develop dynamic analysis technologies regarding the design of offshore wind turbine generators (OWTGs, a special project called Offshore Code Comparison Collaboration Continuation (OC4 was conducted by IEA (International Energy Agency in 2010. A similar project named INER-OC4 has been performed by the Institute of Nuclear Energy Research (INER to develop the OWTG technologies of Taiwan. Since the jacket substructure will be applied to Taiwan OWTGs before 2020, the INER-OC4 project has been devoted to the design and analysis of jacket support structure. In this work, the preliminary result of INER-OC4 is presented. A simplified analysis procedure for jacket support structure has been proposed. Both of the NREL (National Renewable Energy Laboratory 5 MW OWTG FAST model and OC4 jacket substructure model have been built and analyzed under severe design load cases (DLCs of IEC (International Electrotechnical commission 61400-3. Simulation results of six severe DLCs are performed in this work and the results are in agreement with the requirements of API (American Petroleum Institute and NORSOK (Norwegian Petroleum Industry standards.

Substitutions in conserved regions preceding and within the linker affect activity and flexibility of tRNase ZL, the long form of tRNase Z.

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Makenzie Saoura

Full Text Available The enzyme tRNase Z, a member of the metallo-β-lactamase family, endonucleolytically removes 3' trailers from precursor tRNAs, preparing them for CCA addition and aminoacylation. The short form of tRNase Z, tRNase ZS, functions as a homodimer and is found in all prokaryotes and some eukaryotes. The long form, tRNase ZL, related to tRNase ZS through tandem duplication and found only in eukaryotes, possesses ~2,000-fold greater catalytic efficiency than tRNase ZS. tRNase ZL consists of related but diverged amino and carboxy domains connected by a flexible linker (also referred to as a flexible tether and functions as a monomer. The amino domain retains the flexible arm responsible for substrate recognition and binding while the carboxy domain retains the active site. The linker region was explored by Ala-scanning through two conserved regions of D. melanogaster tRNase Z: NdomTprox, located at the carboxy end of the amino domain proximal to the linker, and Tflex, a flexible site in the linker. Periodic substitutions in a hydrophobic patch (F329 and L332 at the carboxy end of NdomTprox show 2,700 and 670-fold impairment relative to wild type, respectively, accompanied by reduced linker flexibility at N-T inside the Ndom- linker boundary. The Ala substitution for N378 in the Tflex region has 10-fold higher catalytic efficiency than wild type and locally decreased flexibility, while the Ala substitution at R382 reduces catalytic efficiency ~50-fold. These changes in pre-tRNA processing kinetics and protein flexibility are interpreted in light of a recent crystal structure for S. cerevisiae tRNase Z, suggesting transmission of local changes in hydrophobicity into the skeleton of the amino domain.

Directing the breathing behavior of pillared-layered metal-organic frameworks via a systematic library of functionalized linkers bearing flexible substituents.

Science.gov (United States)

Henke, Sebastian; Schneemann, Andreas; Wütscher, Annika; Fischer, Roland A

2012-06-06

Flexible metal-organic frameworks (MOFs), also referred to as soft porous crystals (SPCs), show reversible structural transitions dependent on the nature and quantity of adsorbed guest molecules. In recent studies it has been reported that covalent functionalization of the organic linker can influence or even integrate framework flexibility ("breathing") in MOFs. However, rational fine-tuning of such responsive properties is very desirable but challenging as well. Here we present a powerful approach for the targeted manipulation of responsiveness and framework flexibility of an important family of pillared-layered MOFs based on the parent structure [Zn(2)(bdc)(2)(dabco)](n) (bdc = 1,4-benzenedicarboxylate; dabco = 1,4-diazabicyclo[2.2.2]octane). A library of functionalized bdc-type linkers (fu-bdc), which bear additional dangling side groups at different positions of the benzene core (alkoxy groups of varying chain length with diverse functionalities and polarity), was generated. Synthesis of the materials [Zn(2)(fu-bdc)(2)(dabco)](n) yields the respective collection of highly responsive MOFs. The parent MOF is only weakly flexible; however, the substituted frameworks of [Zn(2)(fu-bdc)(2)(dabco)](n) contract drastically upon guest removal and expand again upon adsorption of DMF (N,N-dimethylformamide), EtOH, or CO(2), etc., while N(2) is hardly adsorbed and does not open the narrow-pored form. These "breathing" dynamics are attributed to the dangling side chains that act as immobilized "guests", which interact with mobile guest molecules as well as with themselves and with the framework backbone. The structural details of the guest-free, contracted form and the gas sorption behavior (phase transition pressure, hysteresis loop) are highly dependent on the nature of the substituent at the linker and can therefore be adjusted using our approach. Combining our library of functionalized linkers with the concept of mixed-component MOFs (solid solutions) offers very rich

Synthetic incorporation of Nile Blue into DNA using 2′-deoxyriboside substitutes: Representative comparison of (R- and (S-aminopropanediol as an acyclic linker

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Daniel Lachmann

2010-02-01

Full Text Available The Nile Blue chromophore was incorporated into oligonucleotides using “click” chemistry for the postsynthetic modification of oligonucleotides. These were synthesized using DNA building block 3 bearing an alkyne group and reacted with the azide 4. (R-3-amino-1,2-propanediol was applied as the linker between the phosphodiester bridges. Two sets of DNA duplexes were prepared. One set carried the chromophore in an A-T environment, the second set in a G-C environment. Both were characterized by optical spectroscopy. Sequence-dependent fluorescence quenching was applied as a sensitive tool to compare the stacking interactions with respect to the chirality of the acyclic linker attachment. The results were compared to recent results from duplexes that carried the Nile Blue label in a sequentially and structurally identical context, except for the opposite chirality of the linker ((S-3-amino-1,2-propandiol. Only minor, negligible differences were observed. Melting temperatures, UV–vis absorption spectra together with fluorescence quenching data indicate that Nile Blue stacks perfectly between the adjacent base pairs regardless of whether it has been attached via an S- or R-configured linker. This result was supported by geometrically optimized DNA models.

Soil-structure interaction analysis of NPP containments: substructure and frequency domain methods

International Nuclear Information System (INIS)

Venancio-Filho, F.; Almeida, M.C.F.; Ferreira, W.G.; De Barros, F.C.P.

1997-01-01

Substructure and frequency domain methods for soil-structure interaction are addressed in this paper. After a brief description of mathematical models for the soil and of excitation, the equations for dynamic soil-structure interaction are developed for a rigid surface foundation and for an embedded foundation. The equations for the frequency domain analysis of MDOF systems are provided. An example of soil-structure interaction analysis with frequency-dependent soil properties is given and examples of identification of foundation impedance functions and soil properties are presented. (orig.)

The First MS-Cleavable, Photo-Thiol-Reactive Cross-Linker for Protein Structural Studies

Science.gov (United States)

Iacobucci, Claudio; Piotrowski, Christine; Rehkamp, Anne; Ihling, Christian H.; Sinz, Andrea

2018-04-01

Cleavable cross-linkers are gaining increasing importance for chemical cross-linking/mass spectrometry (MS) as they permit a reliable and automated data analysis in structural studies of proteins and protein assemblies. Here, we introduce 1,3-diallylurea (DAU) as the first CID-MS/MS-cleavable, photo-thiol-reactive cross-linker. DAU is a commercially available, inexpensive reagent that efficiently undergoes an anti-Markovnikov hydrothiolation with cysteine residues in the presence of a radical initiator upon UV-A irradiation. Radical cysteine cross-linking proceeds via an orthogonal "click reaction" and yields stable alkyl sulfide products. DAU reacts at physiological pH and cross-linking reactions with peptides, and proteins can be performed at temperatures as low as 4 °C. The central urea bond is efficiently cleaved upon collisional activation during tandem MS experiments generating characteristic product ions. This improves the reliability of automated cross-link identification. Different radical initiators have been screened for the cross-linking reaction of DAU using the thiol-containing compounds cysteine and glutathione. Our concept has also been exemplified for the biologically relevant proteins bMunc13-2 and retinal guanylyl cyclase-activating protein-2. [Figure not available: see fulltext.

Population structure analysis using rare and common functional variants

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Ding Lili

2011-11-01

Full Text Available Abstract Next-generation sequencing technologies now make it possible to genotype and measure hundreds of thousands of rare genetic variations in individuals across the genome. Characterization of high-density genetic variation facilitates control of population genetic structure on a finer scale before large-scale genotyping in disease genetics studies. Population structure is a well-known, prevalent, and important factor in common variant genetic studies, but its relevance in rare variants is unclear. We perform an extensive population structure analysis using common and rare functional variants from the Genetic Analysis Workshop 17 mini-exome sequence. The analysis based on common functional variants required 388 principal components to account for 90% of the variation in population structure. However, an analysis based on rare variants required 532 significant principal components to account for similar levels of variation. Using rare variants, we detected fine-scale substructure beyond the population structure identified using common functional variants. Our results show that the level of population structure embedded in rare variant data is different from the level embedded in common variant data and that correcting for population structure is only as good as the level one wishes to correct.

Ab initio study of hydrogen adsorption on benzenoid linkers in metal-organic framework materials

International Nuclear Information System (INIS)

Gao Yi; Zeng, X C

2007-01-01

We have computed the energies of adsorption of molecular hydrogen on a number of molecular linkers in metal-organic framework solid materials using density functional theory (DFT) and ab initio molecular orbital methods. We find that the hybrid B3LYP (Becke three-parameter Lee-Yang-Parr) DFT method gives a qualitatively incorrect prediction of the hydrogen binding with benzenoid molecular linkers. Both local-density approximation (LDA) and generalized gradient approximation (GGA) DFT methods are inaccurate in predicting the values of hydrogen binding energies, but can give a qualitatively correct prediction of the hydrogen binding. When compared to the more accurate binding-energy results based on the ab initio Moeller-Plesset second-order perturbation (MP2) method, the LDA results may be viewed as an upper limit while the GGA results may be viewed as a lower limit. Since the MP2 calculation is impractical for realistic metal-organic framework systems, the combined LDA and GGA calculations provide a cost-effective way to assess the hydrogen binding capability of these systems

A Small Number of Residues Can Determine if Linker Histones Are Bound On or Off Dyad in the Chromatosome.

Science.gov (United States)

Zhou, Bing-Rui; Feng, Hanqiao; Ghirlando, Rodolfo; Li, Shipeng; Schwieters, Charles D; Bai, Yawen

2016-10-09

Linker histones bind to the nucleosome and regulate the structure and function of chromatin. We have previously shown that the globular domains of chicken H5 and Drosophila H1 linker histones bind to the nucleosome with on- or off-dyad modes, respectively. To explore the determinant for the distinct binding modes, we investigated the binding of a mutant globular domain of H5 to the nucleosome. This mutant, termed GH5_pMut, includes substitutions of five globular domain residues of H5 with the corresponding residues in the globular domain of Drosophila H1. The residues at these five positions play important roles in nucleosome binding by either H5 or Drosophila H1. NMR and spin-labeling experiments showed that GH5_pMut bound to the nucleosome off the dyad. We further found that the nucleosome array condensed by either the GH5_pMut or the globular domain of Drosophila H1 displayed a similar sedimentation coefficient, whereas the same nucleosome array condensed by the wild-type globular domain of H5 showed a much larger sedimentation coefficient. Moreover, NMR and spin-labeling results from the study of the nucleosome in complex with the full-length human linker histone H1.0, whose globular domain shares high sequence conservation with the corresponding globular domain of H5, are consistent with an on-dyad binding mode. Taken together, our results suggest that a small number of residues in the globular domain of a linker histone can control its binding location on the nucleosome and higher-order chromatin structure. Copyright © 2016. Published by Elsevier Ltd.

Exclusive processes: Tests of coherent QCD phenomena and nucleon substructure at CEBAF

International Nuclear Information System (INIS)

Brodsky, S.J.

1994-07-01

Measurements of exclusive processes such as electroproduction, photoproduction, and Compton scattering are among the most sensitive probes of proton structure and coherent phenomena in quantum chromodynamics. The continuous electron beam at CEBAF, upgraded in laboratory energy to 10--12 GeV, will allow a systematic study of exclusive, semi-inclusive, and inclusive reactions in a kinematic range well-tuned to the study of fundamental nucleon and nuclear substructure. I also discuss the potential at CEBAF for studying novel QCD phenomena at the charm production threshold, including the possible production of nuclear-bound quarkonium

Crystal structure of the Src family kinase Hck SH3-SH2 linker regulatory region supports an SH3-dominant activation mechanism.

Science.gov (United States)

Alvarado, John J; Betts, Laurie; Moroco, Jamie A; Smithgall, Thomas E; Yeh, Joanne I

2010-11-12

Most mammalian cell types depend on multiple Src family kinases (SFKs) to regulate diverse signaling pathways. Strict control of SFK activity is essential for normal cellular function, and loss of kinase regulation contributes to several forms of cancer and other diseases. Previous x-ray crystal structures of the SFKs c-Src and Hck revealed that intramolecular association of their Src homology (SH) 3 domains and SH2 kinase linker regions has a key role in down-regulation of kinase activity. However, the amino acid sequence of the Hck linker represents a suboptimal ligand for the isolated SH3 domain, suggesting that it may form the polyproline type II helical conformation required for SH3 docking only in the context of the intact structure. To test this hypothesis directly, we determined the crystal structure of a truncated Hck protein consisting of the SH2 and SH3 domains plus the linker. Despite the absence of the kinase domain, the structures and relative orientations of the SH2 and SH3 domains in this shorter protein were very similar to those observed in near full-length, down-regulated Hck. However, the SH2 kinase linker adopted a modified topology and failed to engage the SH3 domain. This new structure supports the idea that these noncatalytic regions work together as a "conformational switch" that modulates kinase activity in a manner unique to the SH3 domain and linker topologies present in the intact Hck protein. Our results also provide fresh structural insight into the facile induction of Hck activity by HIV-1 Nef and other Hck SH3 domain binding proteins and implicate the existence of innate conformational states unique to individual Src family members that "fine-tune" their sensitivities to activation by SH3-based ligands.

Alkoxyl- and carbon-centered radicals as primary agents for degrading non-phenolic lignin-substructure model compounds.

Science.gov (United States)

Ohashi, Yasunori; Uno, Yukiko; Amirta, Rudianto; Watanabe, Takahito; Honda, Yoichi; Watanabe, Takashi

2011-04-07

Lignin degradation by white-rot fungi proceeds via free radical reaction catalyzed by oxidative enzymes and metabolites. Basidiomycetes called selective white-rot fungi degrade both phenolic and non-phenolic lignin substructures without penetration of extracellular enzymes into the cell wall. Extracellular lipid peroxidation has been proposed as a possible ligninolytic mechanism, and radical species degrading the recalcitrant non-phenolic lignin substructures have been discussed. Reactions between the non-phenolic lignin model compounds and radicals produced from azo compounds in air have previously been analysed, and peroxyl radical (PR) is postulated to be responsible for lignin degradation (Kapich et al., FEBS Lett., 1999, 461, 115-119). However, because the thermolysis of azo compounds in air generates both a carbon-centred radical (CR) and a peroxyl radical (PR), we re-examined the reactivity of the three radicals alkoxyl radical (AR), CR and PR towards non-phenolic monomeric and dimeric lignin model compounds. The dimeric lignin model compound is degraded by CR produced by reaction of 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), which under N(2) atmosphere cleaves the α-β bond in 1-(4-ethoxy-3-methoxyphenyl)-2-(2-methoxyphenoxy)-1,3-propanediol to yield 4-ethoxy-3-methoxybenzaldehyde. However, it is not degraded by the PR produced by reaction of Ce(4+)/tert-BuOOH. In addition, it is degraded by AR produced by reaction of Ti(3+)/tert-BuOOH. PR and AR are generated in the presence and absence of veratryl alcohol, respectively. Rapid-flow ESR analysis of the radical species demonstrates that AR but not PR reacts with the lignin model compound. Thus, AR and CR are primary agents for the degradation of non-phenolic lignin substructures.

Sub-structure formation in starless cores

Science.gov (United States)

Toci, C.; Galli, D.; Verdini, A.; Del Zanna, L.; Landi, S.

2018-02-01

Motivated by recent observational searches of sub-structure in starless molecular cloud cores, we investigate the evolution of density perturbations on scales smaller than the Jeans length embedded in contracting isothermal clouds, adopting the same formalism developed for the expanding Universe and the solar wind. We find that initially small amplitude, Jeans-stable perturbations (propagating as sound waves in the absence of a magnetic field) are amplified adiabatically during the contraction, approximately conserving the wave action density, until they either become non-linear and steepen into shocks at a time tnl, or become gravitationally unstable when the Jeans length decreases below the scale of the perturbations at a time tgr. We evaluate analytically the time tnl at which the perturbations enter the non-linear stage using a Burgers' equation approach, and we verify numerically that this time marks the beginning of the phase of rapid dissipation of the kinetic energy of the perturbations. We then show that for typical values of the rms Mach number in molecular cloud cores, tnl is smaller than tgr, and therefore density perturbations likely dissipate before becoming gravitational unstable. Solenoidal modes grow at a faster rate than compressible modes, and may eventually promote fragmentation through the formation of vortical structures.

Micromachined silicon acoustic delay line with 3D-printed micro linkers and tapered input for improved structural stability and acoustic directivity

International Nuclear Information System (INIS)

Cho, Y; Kumar, A; Xu, S; Zou, J

2016-01-01

Recent studies have shown that micromachined silicon acoustic delay lines can provide a promising solution to achieve real-time photoacoustic tomography without the need for complex transducer arrays and data acquisition electronics. To achieve deeper imaging depth and wider field of view, a longer delay time and therefore delay length are required. However, as the length of the delay line increases, it becomes more vulnerable to structural instability due to reduced mechanical stiffness. In this paper, we report the design, fabrication, and testing of a new silicon acoustic delay line enhanced with 3D printed polymer micro linker structures. First, mechanical deformation of the silicon acoustic delay line (with and without linker structures) under gravity was simulated by using finite element method. Second, the acoustic crosstalk and acoustic attenuation caused by the polymer micro linker structures were evaluated with both numerical simulation and ultrasound transmission testing. The result shows that the use of the polymer micro linker structures significantly improves the structural stability of the silicon acoustic delay lines without creating additional acoustic attenuation and crosstalk. In addition, the improvement of the acoustic acceptance angle of the silicon acoustic delay lines was also investigated to better suppress the reception of unwanted ultrasound signals outside of the imaging plane. These two improvements are expected to provide an effective solution to eliminate current limitations on the achievable acoustic delay time and out-of-plane imaging resolution of micromachined silicon acoustic delay line arrays. (paper)

Motion and deformation estimation from medical imagery by modeling sub-structure interaction and constraints

KAUST Repository

Sundaramoorthi, Ganesh

2012-09-13

This paper presents a novel medical image registration algorithm that explicitly models the physical constraints imposed by objects or sub-structures of objects that have differing material composition and border each other, which is the case in most medical registration applications. Typical medical image registration algorithms ignore these constraints and therefore are not physically viable, and to incorporate these constraints would require prior segmentation of the image into regions of differing material composition, which is a difficult problem in itself. We present a mathematical model and algorithm for incorporating these physical constraints into registration / motion and deformation estimation that does not require a segmentation of different material regions. Our algorithm is a joint estimation of different material regions and the motion/deformation within these regions. Therefore, the segmentation of different material regions is automatically provided in addition to the image registration satisfying the physical constraints. The algorithm identifies differing material regions (sub-structures or objects) as regions where the deformation has different characteristics. We demonstrate the effectiveness of our method on the analysis of cardiac MRI which includes the detection of the left ventricle boundary and its deformation. The experimental results indicate the potential of the algorithm as an assistant tool for the quantitative analysis of cardiac functions in the diagnosis of heart disease.

Quark substructure approach to 4He charge distribution

International Nuclear Information System (INIS)

Wilets, L.; Alberg, M.A.; Pepin, S.; Stancu, F.; Carlson, J.; Koepf, W.

1997-01-01

We present a study of the 4 He charge distribution based on realistic nucleonic wave functions and incorporation of quark substructure. Any central depression of the proton point density seen in modern four-body calculations is too small by itself to lead to a correct description of the charge distribution of 4 He if folded with a fixed proton size parameter, as is usually done. We utilize six-quark structures calculated in the chromodielectric model for N-N interactions to find a swelling of the proton size as the internucleon distance decreases. This swelling is a result of the short-range dynamics in the N-N system. Using the independent pair approximation, the corresponding charge distribution of the proton is folded with the two-nucleon distribution generated from Green's function Monte Carlo calculations of the 4 He nucleonic wave function. We obtain a reasonably good fit to the experimental charge distribution of 4 He. Meson-exchange currents have not been included. copyright 1997 The American Physical Society

Yeast linker histone Hho1p is required for efficient RNA polymerase I processivity and transcriptional silencing at the ribosomal DNA

OpenAIRE

Levy, Anat; Eyal, Miri; Hershkovits, Gitit; Salmon-Divon, Mali; Klutstein, Michael; Katcoff, Don Jay

2008-01-01

Nucleosome core particles in eukaryotes are linked by a stretch of DNA that is usually associated with a linker histone. Here, we show in yeast, that the presence of yeast linker histone Hho1p represses expression of a pol II transcribed gene (MET15) embedded in the rDNA. In vivo deletions of Hho1p sequences showed that the second globular domain is sufficient for that repression, whereas the presence of the N terminus is required for its derepression. In contrast, a run-on assay confirmed by...

Mechanical properties and related substructure of TiNi shape memory alloys

International Nuclear Information System (INIS)

Filip, P.; Kneissl, A.C.

1995-01-01

The mechanical properties of binary near equiatomic TiNi shape memory alloys were investigated after different types of mechanical and heat treatments. The changes of deformation behaviour are explained on the basis of substructure differences after work hardening. The ''elastic moduli'' of both the high-temperature phase B2 and the martensite B19' as well as the ''easy stage of deformation'' are dependent on the work hardening intensity and these changes are related to the mobility of B2/B19' interfaces. The martensite changes its morphology after work hardening. In contrast to a twinned martensite, typical for annealed alloys, the internally slipped martensite was detected after work hardening. (orig.)

Mutations in B3GALT6, which Encodes a Glycosaminoglycan Linker Region Enzyme, Cause a Spectrum of Skeletal and Connective Tissue Disorders

OpenAIRE

Nakajima, Masahiro; Mizumoto, Shuji; Miyake, Noriko; Kogawa, Ryo; Iida, Aritoshi; Ito, Hironori; Kitoh, Hiroshi; Hirayama, Aya; Mitsubuchi, Hiroshi; Miyazaki, Osamu; Kosaki, Rika; Horikawa, Reiko; Lai, Angeline; Mendoza-Londono, Roberto; Dupuis, Lucie

2013-01-01

Proteoglycans (PGs) are a major component of the extracellular matrix in many tissues and function as structural and regulatory molecules. PGs are composed of core proteins and glycosaminoglycan (GAG) side chains. The biosynthesis of GAGs starts with the linker region that consists of four sugar residues and is followed by repeating disaccharide units. By exome sequencing, we found that B3GALT6 encoding an enzyme involved in the biosynthesis of the GAG linker region is responsible for a sever...

Estimation of the displacement of cardiac substructures and the motion of the coronary arteries using electrocardiographic gating

Directory of Open Access Journals (Sweden)

Tan W

2013-09-01

Full Text Available Wenyong Tan,1,* Liying Xu,2,* Xiaohong Wang,1 Dasheng Qiu,3 Guang Han,1 Desheng Hu1 1Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan, People’s Republic of China; 2Department of Radiology, Zhongnan Hospital, Wuhan University, Wuhan, People’s Republic of China; 3PET-CT Center, Hubei Cancer Hospital, Wuhan, People’s Republic of China *These authors have contributed equally to this paper Purpose: The aim of this study was to quantify the displacement of cardiac substructures, including the anterior myocardial territory (AMT, left ventricle, and coronary arteries during a normal cardiac cycle. Materials and methods: Computed tomography (CT images with retrospective electrocardiographic gating of 17 eligible patients were obtained. All images were reconstructed automatically for the end-diastolic and end-systolic phases. CT scanning without contrast at a random phase and a selected vertebral body were used as references to measure three-dimensionaldisplacements of the cardiac substructures. Results: The displacement between the end-diastolic and end-systolic phases (Dd-s was greater than that between the end-systolic and random phases and between the end-diastolic and random cardiac phases. The largest displacements for the heart were in the left, posterior, and inferior directions with an average Dd-s of approximately 4–6 mm. The average Dd-s for the AMT and left ventricle was 1.2–2.7 mm in the anterior and right directions, 4.3–7.8 mm in left and posterior directions, and 4.9–6.3 mm in superior and inferior directions. For the coronary arteries, the average Dd-s was 2.8–5.9 mm in the anterior-posterior direction, 3.5–6.6 mm in left-right direction, and 3.8–5.3 mm in the superior-inferior direction. Inter-observer agreement was excellent for the heart, AMT, and left ventricle (kappa coefficient, >0.75 for all and good for most coronary arteries in three dimensions (kappa coefficient, 0.511–0.687. The Dd-s did not

Design of Tail-Clamp Peptide Nucleic Acid Tethered with Azobenzene Linker for Sequence-Specific Detection of Homopurine DNA

Directory of Open Access Journals (Sweden)

Shinjiro Sawada

2017-10-01

Full Text Available DNA carries genetic information in its sequence of bases. Synthetic oligonucleotides that can sequence-specifically recognize a target gene sequence are a useful tool for regulating gene expression or detecting target genes. Among the many synthetic oligonucleotides, tail-clamp peptide nucleic acid (TC-PNA offers advantages since it has two homopyrimidine PNA strands connected via a flexible ethylene glycol-type linker that can recognize complementary homopurine sequences via Watson-Crick and Hoogsteen base pairings and form thermally-stable PNA/PNA/DNA triplex structures. Here, we synthesized a series of TC-PNAs that can possess different lengths of azobenzene-containing linkers and studied their binding behaviours to homopurine single-stranded DNA. Introduction of azobenzene at the N-terminus amine of PNA increased the thermal stability of PNA-DNA duplexes. Further extension of the homopyrimidine PNA strand at the N-terminus of PNA-AZO further increased the binding stability of the PNA/DNA/PNA triplex to the target homopurine sequence; however, it induced TC-PNA/DNA/TC-PNA complex formation. Among these TC-PNAs, 9W5H-C4-AZO consisting of nine Watson-Crick bases and five Hoogsteen bases tethered with a beta-alanine conjugated azobenzene linker gave a stable 1:1 TC-PNA/ssDNA complex and exhibited good mismatch recognition. Our design for TC-PNA-AZO can be utilized for detecting homopurine sequences in various genes.

Identification of a minimal functional linker in human topoisomerase I by domain swapping with Cre recombinase

DEFF Research Database (Denmark)

Hougaard, Rikke Frøhlich; Juul, Sissel; Vinther, Maria

2008-01-01

. In this study we replace 86 amino acids including the linker domain of the cellular type IB topoisomerase, human topoisomerase I, with four, six, or eight amino acids from the corresponding short loop region in Cre recombinase. In vitro characterization of the resulting chimeras, denoted Cropos, reveals...

Study of a 900 MW PWR by a substructuring method - Spectral response to a seismic excitation and comparison with a beam model

International Nuclear Information System (INIS)

Rousseau, G.; Bianchini-Burlot, B.; Bosselut, D.; Jacquart, G.; Viallet, E.

1997-03-01

This report presents a three dimensional Finite Element Model (FEM) of a 900 MW Pressurized Water Reactor (PWR) which is described at first: its modal behaviour is computed by a sub-structuring method based upon a Component Mode Synthesis (CMS) method. All the substructures taken into account in the model are described. One model with equivalent beams is also described. Then, different approaches to take into account the fluid/structure interaction in the different models are investigated. Results of the modal analysis of each model are compared to each other and with experimental measures. This modal analysis is then used to compute the non linear and linear response of the PWR due to a seismic excitation. (author)

Governing the management and use of pooled microbial genetic resources: Lessons from the global crop commons

Directory of Open Access Journals (Sweden)

Michael Halewood

2010-01-01

Full Text Available The paper highlights lessons learned over the last thirty years establishing a governance structure for the global crop commons that are of relevance to current champions of the microbial commons. It argues that the political, legal and biophysical situation in which microbial genetic resources (and their users are located today are similar to the situation of plant genetic resources in the mid-1990s, before the International Treaty on Plant Genetic Resources was negotiated. Consequently, the paper suggests that it may be useful to look to the model of global network of ex situ plant genetic resources collections as a precedent to follow – even if only loosely – in developing an intergovernmentally endorsed legal substructure and governance framework for the microbial commons.

The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences

DEFF Research Database (Denmark)

Rivas, Matilde De Las; Lira-Navarrete, Erandi; Daniel, Earnest James Paul

2017-01-01

The polypeptide GalNAc-transferases (GalNAc-Ts), that initiate mucin-type O-glycosylation, consist of a catalytic and a lectin domain connected by a flexible linker. In addition to recognizing polypeptide sequence, the GalNAc-Ts exhibit unique long-range N- A nd/or C-terminal prior glycosylation ...

An algebraic substructuring using multiple shifts for eigenvalue computations

International Nuclear Information System (INIS)

Ko, Jin Hwan; Jung, Sung Nam; Byun, Do Young; Bai, Zhaojun

2008-01-01

Algebraic substructuring (AS) is a state-of-the-art method in eigenvalue computations, especially for large-sized problems, but originally it was designed to calculate only the smallest eigenvalues. Recently, an updated version of AS has been introduced to calculate the interior eigenvalues over a specified range by using a shift concept that is referred to as the shifted AS. In this work, we propose a combined method of both AS and the shifted AS by using multiple shifts for solving a considerable number of eigensolutions in a large-sized problem, which is an emerging computational issue of noise or vibration analysis in vehicle design. In addition, we investigated the accuracy of the shifted AS by presenting an error criterion. The proposed method has been applied to the FE model of an automobile body. The combined method yielded a higher efficiency without loss of accuracy in comparison to the original AS

ATLAS Standard Model Measurements Using Jet Grooming and Substructure

CERN Document Server

Ucchielli, Giulia; The ATLAS collaboration

2017-01-01

Boosted topologies allow to explore Standard Model processes in kinematical regimes never tested before. In such LHC challenging environments, standard reconstruction techniques quickly hit the wall. Targeting hadronic final states means to properly reconstruct energy and multiplicity of the jets in the event. In order to be able to identify the decay product of boosted objects, i.e. W bosons, $t\\bar{t}$ pairs or Higgs produced in association with $t\\bar{t}$ pairs, ATLAS experiment is currently exploiting several algorithms using jet grooming and jet substructure. This contribution will mainly cover the following ATLAS measurements: $t\\bar{t}$ differential cross section production and jet mass using the soft drop procedure. Standard Model measurements offer the perfect field to test the performances of new jet tagging techniques which will become even more important in the search for new physics in highly boosted topologies.”

The influence of peak stress on the mechanical behavior and the substructural evolution in shock-prestrained zirconium

International Nuclear Information System (INIS)

Cerreta, E.; Gray, G.T. III; Henrie, B.L.; Brown, D.W.; Hixson, R.S.; Rigg, P.A.

2004-01-01

The post shock mechanical behavior and substructure evolution of zirconium (Zr) under shock prestrained at 5.8 and 8 GPa, above and below the pressure induced α-ω phase transition, has been quantified. The reload yield stress of Zr shock prestrained to 8 GPa was found to exhibit enhanced shock hardening when compared to the flow stress measured quasi-statically at an equivalent strain. In contrast, the reload yield behavior of Zr specimens shocked to 5.8 GPa did not exhibit enhanced shock hardening. The microstructure of the as-annealed and shock prestrained materials were examined. The presence of a reduced available glide distance due to a relatively more well developed dislocation substructure and increased twinning over quasi-static specimens deformed to comparable strains correlates with the increased yield stresses after shock prestraining at 8 GPa. Additionally, the retention of ∼ 40% by volume metastable high-pressure ω-phase in specimens shocked to 8 GPa and its absence in the 5.8 GPa specimen, is thought to contribute to the increased yield stress in the 8 GPa specimens

Detailed Analysis of Japanese Population Substructure with a Focus on the Southwest Islands of Japan

Science.gov (United States)

Nishiyama, Takeshi; Kishino, Hirohisa; Suzuki, Sadao; Ando, Ryosuke; Niimura, Hideshi; Uemura, Hirokazu; Horita, Mikako; Ohnaka, Keizo; Kuriyama, Nagato; Mikami, Haruo; Takashima, Naoyuki; Mastuo, Keitaro; Guang, Yin; Wakai, Kenji; Hamajima, Nobuyuki; Tanaka, Hideo

2012-01-01

Uncovering population structure is important for properly conducting association studies and for examining the demographic history of a population. Here, we examined the Japanese population substructure using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC), which covers all but the northern region of Japan. Using 222 autosomal loci from 4502 subjects, we investigated population substructure by estimating FST among populations, testing population differentiation, and performing principal component analysis (PCA) and correspondence analysis (CA). All analyses revealed a low but significant differentiation between the Amami Islanders and the mainland Japanese population. Furthermore, we examined the genetic differentiation between the mainland population, Amami Islanders and Okinawa Islanders using six loci included in both the Pan-Asian SNP (PASNP) consortium data and the J-MICC data. This analysis revealed that the Amami and Okinawa Islanders were differentiated from the mainland population. In conclusion, we revealed a low but significant level of genetic differentiation between the mainland population and populations in or to the south of the Amami Islands, although genetic variation between both populations might be clinal. Therefore, the possibility of population stratification must be considered when enrolling the islander population of this area, such as in the J-MICC study. PMID:22509376

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

Energy Technology Data Exchange (ETDEWEB)

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.

Identification of unique interactions between the flexible linker and the RecA-like domains of DEAD-box helicase Mss116

International Nuclear Information System (INIS)

Zhang, Yuan; Palla, Mirkó; Liao, Jung-Chi; Sun, Andrew

2013-01-01

DEAD-box RNA helicases are ATP-dependent proteins implicated in nearly all aspects of RNA metabolism. The yeast DEAD-box helicase Mss116 is unique in its functions of splicing group I and group II introns and activating mRNA translation, but the structural understanding of why it performs these unique functions remains unclear. Here we used sequence analysis and molecular dynamics simulation to identify residues in the flexible linker specific for yeast Mss116, potentially associated with its unique functions. We first identified residues that are 100% conserved in Mss116 of different species of the Saccharomycetaceae family. The amino acids of these conserved residues were then compared with the amino acids of the corresponding residue positions of other RNA helicases to identify residues that have distinct amino acids from other DEAD-box proteins. Four residues in the flexible linker, i.e. N334, E335, P336 and H339, are conserved and Mss116-specific. Molecular dynamics simulation was conducted for the wild-type Mss116 structure and mutant models to examine mutational effects of the linker on the conformational equilibrium. Relatively short MD simulation runs (within 20 ns) were enough for us to observe mutational effects, suggesting serious structural perturbations by these mutations. The mutation of E335 depletes the interactions between E335 and K95 in domain 1. The interactions between N334/P336 and N496/I497 of domain 2 are also abolished by mutation. Our results suggest that tight interactions between the Mss116-specific flexible linker and the two RecA-like domains may be mechanically required to crimp RNA for the unique RNA processes of yeast Mss116. (paper)

Identification of unique interactions between the flexible linker and the RecA-like domains of DEAD-box helicase Mss116

Science.gov (United States)

Zhang, Yuan; Palla, Mirkó; Sun, Andrew; Liao, Jung-Chi

2013-09-01

DEAD-box RNA helicases are ATP-dependent proteins implicated in nearly all aspects of RNA metabolism. The yeast DEAD-box helicase Mss116 is unique in its functions of splicing group I and group II introns and activating mRNA translation, but the structural understanding of why it performs these unique functions remains unclear. Here we used sequence analysis and molecular dynamics simulation to identify residues in the flexible linker specific for yeast Mss116, potentially associated with its unique functions. We first identified residues that are 100% conserved in Mss116 of different species of the Saccharomycetaceae family. The amino acids of these conserved residues were then compared with the amino acids of the corresponding residue positions of other RNA helicases to identify residues that have distinct amino acids from other DEAD-box proteins. Four residues in the flexible linker, i.e. N334, E335, P336 and H339, are conserved and Mss116-specific. Molecular dynamics simulation was conducted for the wild-type Mss116 structure and mutant models to examine mutational effects of the linker on the conformational equilibrium. Relatively short MD simulation runs (within 20 ns) were enough for us to observe mutational effects, suggesting serious structural perturbations by these mutations. The mutation of E335 depletes the interactions between E335 and K95 in domain 1. The interactions between N334/P336 and N496/I497 of domain 2 are also abolished by mutation. Our results suggest that tight interactions between the Mss116-specific flexible linker and the two RecA-like domains may be mechanically required to crimp RNA for the unique RNA processes of yeast Mss116.

Radioiodination of protein using 2,3,5,6-tetrafluorophenyl 3-(nido-carboranyl) propionate (TCP) as a potential bi-functional linker: Synthesis and biodistribution in mice

International Nuclear Information System (INIS)

Lin Rushan; Liu Ning; Yang Yuanyou; Li Bing; Liao Jiali; Jin Jiannan

2009-01-01

2,3,5,6-Tetrafluorophenyl 3-(nido-carboranyl) propionate (TCP), as a new potential bi-functional linker for radiohalogenation of proteins or peptides, was synthesized. With this bi-functional linker, the first attempt to conjugate bovine serum albumin (BSA) with 125 I was made and the biodistribution of the conjugated BSA ( 125 I-TCP-BSA) was investigated in NIH strain mice. By the use of TCP as the linker, BSA was conjugated with 125 I in a labeling yield of 58-75% and with radiochemical purity of 99.8% after purification by Sephadex TM G-50. Even after being kept at room temperature for 72 h, the radiochemical purity of 125 I-TCP-BSA was still more than 98%, much higher than that of the directly 125 I-labeled BSA ( 125 I-BSA). Meanwhile, biodistribution experiments in mice indicated that the uptake of 125 I with 125 I-TCP-BSA into thyroid was obviously less than that with 125 I-BSA post-injection. All the results implied that the 125 I-conjugated BSA ( 125 I-TCP-BSA) was considerably stable in vivo as well as in vitro, and TCP was regarded as a promising bi-functional linker for radiohalogenation of proteins

Optimization of the Alkyl Linker of TO Base Surrogate in Triplex-Forming PNA for Enhanced Binding to Double-Stranded RNA.

Science.gov (United States)

Sato, Takaya; Sato, Yusuke; Nishizawa, Seiichi

2017-03-23

A series of triplex-forming peptide nucleic acid (TFP) probes carrying a thiazole orange (TO) base surrogate through an alkyl linker was synthesized, and the interactions between these so-called tFIT probes and purine-rich sequences within double-stranded RNA (dsRNA) were examined. We found that the TO base surrogate linker significantly affected both the binding affinity and the fluorescence response upon triplex formation with the target dsRNA. Among the probes examined, the TO base surrogate connected through the propyl linker in the tFIT probes increased the binding affinity by a factor of ten while maintaining its function as the fluorescent universal base. Isothermal titration calorimetry experiments revealed that the increased binding affinity resulted from the gain in the binding enthalpy, which could be explained by the enhanced π-stacking interaction between the TO base surrogate and the dsRNA part of the triplex. We expect that these results will provide a molecular basis for designing strong binding tFIT probes for fluorescence sensing of various kinds of purine-rich dsRNAs sequences including those carrying a pyrimidine-purine inversion. The obtained data also offers a new insight into further development of the universal bases incorporated in TFP. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hybrid Zeolitic Imidazolate Frameworks: Controlling Framework Porosity and Functionality by Mixed-Linker Synthesis

KAUST Repository

Thompson, Joshua A.

2012-05-22

Zeolitic imidazolate frameworks (ZIFs) are a subclass of nanoporous metal-organic frameworks (MOFs) that exhibit zeolite-like structural topologies and have interesting molecular recognition properties, such as molecular sieving and gate-opening effects associated with their pore apertures. The synthesis and characterization of hybrid ZIFs with mixed linkers in the framework are described in this work, producing materials with properties distinctly different from the parent frameworks (ZIF-8, ZIF-90, and ZIF-7). NMR spectroscopy is used to assess the relative amounts of the different linkers included in the frameworks, whereas nitrogen physisorption shows the evolution of the effective pore size distribution in materials resulting from the framework hybridization. X-ray diffraction shows these hybrid materials to be crystalline. In the case of ZIF-8-90 hybrids, the cubic space group of the parent frameworks is continuously maintained, whereas in the case of the ZIF-7-8 hybrids there is a transition from a cubic to a rhombohedral space group. Nitrogen physisorption data reveal that the hybrid materials exhibit substantial changes in gate-opening phenomena, either occurring at continuously tunable partial pressures of nitrogen (ZIF-8-90 hybrids) or loss of gate-opening effects to yield more rigid frameworks (ZIF-7-8 hybrids). With this synthetic approach, significant alterations in MOF properties may be realized to suit a desired separation or catalytic process. © 2012 American Chemical Society.

A Switchable Linker-Based Immunoassay for Ultrasensitive Visible Detection of Salmonella in Tomatoes.

Science.gov (United States)

Hahn, Jungwoo; Kim, Eunghee; You, Young Sang; Gunasekaran, Sundaram; Lim, Seokwon; Choi, Young Jin

2017-10-01

On-site detection for sensitive identification of foodborne pathogens on fresh produce with minimal use of specialized instrumentation is crucial to the food industry. A switchable linker (SL)-based immunoassay was designed for ultrasensitive on-site detection of Salmonella in tomato samples. The assay is based on large-scale aggregation of gold nanoparticles (GNPs), induced by a quantitative relationship among the biotinylated Salmonella polyclonal antibody (b-Ab) used as the SL, the functionalized GNPs, and Salmonella. Important factors such as the concentration of SLs, time required for large-scale aggregation, and selectivity of b-Ab were optimized to minimize the detection time (within 45 min with gentle agitation) and achieve the lowest limit of detection (LOD; 10 CFU/g in tomato samples) possible. This SL-based immunoassay with its relatively low LOD and short detection time may meet the need for rapid, simple, on-site analysis of pathogens in fresh produce. The novel switchable linker-based immunoassay is a rapid, specific, and sensitive method that has potential applications for routine diagnostics of Salmonella in tomato products. These advantages make it a practical approach for general use in the processing industry to detect Salmonella rapidly and to implement appropriate regulatory procedures. Furthermore, it could be applied to other fresh products including cantaloupe, strawberry, and cucumbers. © 2017 Institute of Food Technologists®.

Magnetic field influence on substructure formed by electric spark treatment

International Nuclear Information System (INIS)

Reza Rahbari, G.; Ivanov, A.N.

1996-01-01

The substructure of surface layer (about 10 microns thick) has been studied by x-ray line broadening technique in the samples of plain carbon steel (0.45%C) after electric spark doping with and without magnetic field (MF). The applied spark pulse energy was 0.12 J and MF induction varied from 0 to 0.08 T. The electrode material was the same as that of the treated sample. It has been observed that the MF reduces the tensile residual surface stresses from 660 ± 15MPa (no MF) to 260 ± 15MPa (B=0.053 T). The analysis of x-ray line broadening has revealed only the existence of microstrains, which are dependent of the MF magnitude. The microstrains have been related to the randomly distributed dislocation with the density of about 3x10 sup 11 cm sup -2

Definition of a concrete bio-decontamination process in nuclear substructures

International Nuclear Information System (INIS)

Jestin, A.

2005-05-01

The decontamination of sub-structural materials represents a stake of high-importance because of the high volume generated. It is agreed then to propose efficient and effective processes. The process of bio-decontamination of the hydraulic binders leans on the mechanisms of biodegradation of concretes, phenomenon characterized in the 40's by an indirect attack of the material by acids stem from the microbial metabolism: sulphuric acid (produced by Thiobacillus), nitric acid (produced by Nitrosomonas and Nitrobacter) and organic acids (produced by fungi). The principle of the bio-decontamination process is to apply those micro-organisms on the surface of the contaminated material, in order to damage its surface and to retrieve the radionuclides. One of the multiple approaches of the process is the use of a bio-gel that makes possible the micro-organisms application. (author)

An intrinsically disordered linker controlling the formation and the stability of the bacterial flagellar hook

OpenAIRE

Barker, Clive S.; Meshcheryakova, Irina V.; Kostyukova, Alla S.; Freddolino, Peter L.; Samatey, Fadel A.

2017-01-01

Background In a macro-molecular complex, any minor change may prove detrimental. For a supra-molecular nano-machine like the bacterial flagellum, which consists of several distinct parts with specific characteristics, stability is important. During the rotation of the bacterial flagellar motor, which is located in the membrane, the flagella rotate at speeds between 200 and 2000 rpm, depending on the bacterial species. The hook substructure of the bacterial flagellum acts as a universal joint ...

Nuclear sub-structure in 112–122Ba nuclei within relativistic mean field theory

International Nuclear Information System (INIS)

Bhuyan, M.; Patra, S.K.; Arumugam, P.; Gupta, Raj K.

2011-01-01

Working within the framework of relativistic mean field theory, we study for the first time the clustering structure (nuclear sub-structure) of 112–122 Ba nuclei in an axially deformed cylindrical coordinate. We calculate the individual neutrons and protons density distributions for Ba-isotopes. From the analysis of the clustering configurations in total (neutrons-plus-protons) density distributions for various shapes of both the ground and excited states, we find different sub-structures inside the Ba nuclei considered here. The important step, carried out here for the first time, is the counting of number of protons and neutrons present in the clustering region(s). 12 C is shown to constitute the cluster configuration in prolate-deformed ground-states of 112–116 Ba and oblate-deformed first excited states of 118–122 Ba nuclei. Presence of other lighter clusters such as 2 H, 3 H and nuclei in the neighborhood of N = Z, 14 N, 34–36 Cl, 36 Ar and 42 Ca are also indicated in the ground and excited states of these nuclei. Cases with no cluster configuration are shown for 112–116 Ba in their first and second excited states. All these results are of interest for the observed intermediate-mass-fragments and fusion–fission processes, and the so far unobserved evaporation residues from the decaying Ba* compound nuclei formed in heavy ion reactions. (author)

Learning a Weighted Sequence Model of the Nucleosome Core and Linker Yields More Accurate Predictions in Saccharomyces cerevisiae and Homo sapiens

Science.gov (United States)

Reynolds, Sheila M.; Bilmes, Jeff A.; Noble, William Stafford

2010-01-01

DNA in eukaryotes is packaged into a chromatin complex, the most basic element of which is the nucleosome. The precise positioning of the nucleosome cores allows for selective access to the DNA, and the mechanisms that control this positioning are important pieces of the gene expression puzzle. We describe a large-scale nucleosome pattern that jointly characterizes the nucleosome core and the adjacent linkers and is predominantly characterized by long-range oscillations in the mono, di- and tri-nucleotide content of the DNA sequence, and we show that this pattern can be used to predict nucleosome positions in both Homo sapiens and Saccharomyces cerevisiae more accurately than previously published methods. Surprisingly, in both H. sapiens and S. cerevisiae, the most informative individual features are the mono-nucleotide patterns, although the inclusion of di- and tri-nucleotide features results in improved performance. Our approach combines a much longer pattern than has been previously used to predict nucleosome positioning from sequence—301 base pairs, centered at the position to be scored—with a novel discriminative classification approach that selectively weights the contributions from each of the input features. The resulting scores are relatively insensitive to local AT-content and can be used to accurately discriminate putative dyad positions from adjacent linker regions without requiring an additional dynamic programming step and without the attendant edge effects and assumptions about linker length modeling and overall nucleosome density. Our approach produces the best dyad-linker classification results published to date in H. sapiens, and outperforms two recently published models on a large set of S. cerevisiae nucleosome positions. Our results suggest that in both genomes, a comparable and relatively small fraction of nucleosomes are well-positioned and that these positions are predictable based on sequence alone. We believe that the bulk of the

Learning a weighted sequence model of the nucleosome core and linker yields more accurate predictions in Saccharomyces cerevisiae and Homo sapiens.

Directory of Open Access Journals (Sweden)

Sheila M Reynolds

2010-07-01

Full Text Available DNA in eukaryotes is packaged into a chromatin complex, the most basic element of which is the nucleosome. The precise positioning of the nucleosome cores allows for selective access to the DNA, and the mechanisms that control this positioning are important pieces of the gene expression puzzle. We describe a large-scale nucleosome pattern that jointly characterizes the nucleosome core and the adjacent linkers and is predominantly characterized by long-range oscillations in the mono, di- and tri-nucleotide content of the DNA sequence, and we show that this pattern can be used to predict nucleosome positions in both Homo sapiens and Saccharomyces cerevisiae more accurately than previously published methods. Surprisingly, in both H. sapiens and S. cerevisiae, the most informative individual features are the mono-nucleotide patterns, although the inclusion of di- and tri-nucleotide features results in improved performance. Our approach combines a much longer pattern than has been previously used to predict nucleosome positioning from sequence-301 base pairs, centered at the position to be scored-with a novel discriminative classification approach that selectively weights the contributions from each of the input features. The resulting scores are relatively insensitive to local AT-content and can be used to accurately discriminate putative dyad positions from adjacent linker regions without requiring an additional dynamic programming step and without the attendant edge effects and assumptions about linker length modeling and overall nucleosome density. Our approach produces the best dyad-linker classification results published to date in H. sapiens, and outperforms two recently published models on a large set of S. cerevisiae nucleosome positions. Our results suggest that in both genomes, a comparable and relatively small fraction of nucleosomes are well-positioned and that these positions are predictable based on sequence alone. We believe that the

Learning a weighted sequence model of the nucleosome core and linker yields more accurate predictions in Saccharomyces cerevisiae and Homo sapiens.

Science.gov (United States)

Reynolds, Sheila M; Bilmes, Jeff A; Noble, William Stafford

2010-07-08

DNA in eukaryotes is packaged into a chromatin complex, the most basic element of which is the nucleosome. The precise positioning of the nucleosome cores allows for selective access to the DNA, and the mechanisms that control this positioning are important pieces of the gene expression puzzle. We describe a large-scale nucleosome pattern that jointly characterizes the nucleosome core and the adjacent linkers and is predominantly characterized by long-range oscillations in the mono, di- and tri-nucleotide content of the DNA sequence, and we show that this pattern can be used to predict nucleosome positions in both Homo sapiens and Saccharomyces cerevisiae more accurately than previously published methods. Surprisingly, in both H. sapiens and S. cerevisiae, the most informative individual features are the mono-nucleotide patterns, although the inclusion of di- and tri-nucleotide features results in improved performance. Our approach combines a much longer pattern than has been previously used to predict nucleosome positioning from sequence-301 base pairs, centered at the position to be scored-with a novel discriminative classification approach that selectively weights the contributions from each of the input features. The resulting scores are relatively insensitive to local AT-content and can be used to accurately discriminate putative dyad positions from adjacent linker regions without requiring an additional dynamic programming step and without the attendant edge effects and assumptions about linker length modeling and overall nucleosome density. Our approach produces the best dyad-linker classification results published to date in H. sapiens, and outperforms two recently published models on a large set of S. cerevisiae nucleosome positions. Our results suggest that in both genomes, a comparable and relatively small fraction of nucleosomes are well-positioned and that these positions are predictable based on sequence alone. We believe that the bulk of the

Dual-purpose linker for alpha helix stabilization and imaging agent conjugation to glucagon-like peptide-1 receptor ligands.

Science.gov (United States)

Zhang, Liang; Navaratna, Tejas; Liao, Jianshan; Thurber, Greg M

2015-02-18

Peptides display many characteristics of efficient imaging agents such as rapid targeting, fast background clearance, and low non-specific cellular uptake. However, poor stability, low affinity, and loss of binding after labeling often preclude their use in vivo. Using glucagon-like peptide-1 receptor (GLP-1R) ligands exendin and GLP-1 as a model system, we designed a novel α-helix-stabilizing linker to simultaneously address these limitations. The stabilized and labeled peptides showed an increase in helicity, improved protease resistance, negligible loss or an improvement in binding affinity, and excellent in vivo targeting. The ease of incorporating azidohomoalanine in peptides and efficient reaction with the dialkyne linker enable this technique to potentially be used as a general method for labeling α helices. This strategy should be useful for imaging beta cells in diabetes research and in developing and testing other peptide targeting agents.

Gamma-ray signatures of annihilation to charged leptons in dark matter substructure

International Nuclear Information System (INIS)

Kistler, Matthew D.; Siegal-Gaskins, Jennifer M.

2010-01-01

Because of their higher concentrations and small internal velocities, Milky Way subhalos can be at least as important as the smooth halo in accounting for the GeV positron excess via dark matter annihilation. After showing how this can be achieved in various scenarios, including in Sommerfeld models, we demonstrate that, in this case, the diffuse inverse-Compton emission resulting from electrons and positrons produced in substructure leads to a nearly-isotropic signal close to the level of the isotropic GeV gamma-ray background seen by Fermi. Moreover, we show that HESS cosmic-ray electron measurements can be used to constrain multi-TeV internal bremsstrahlung gamma rays arising from annihilation to charged leptons.

Spin effects from quark and lepton substructure at future machines

International Nuclear Information System (INIS)

Rueckl, R.

1985-01-01

If quarks and leptons are composite on a distance scale Λ -1 the physics at energies larger than Λ will provide plenty of evidence for the new level of substructure. However, already at energies below Λ compositeness should become manifest in deviations from the standard model due to form factors, residual interactions and, possibly, new ''light'' states. I discuss the virtue of polarized lepton and hadron beams in searching for new interactions and exemplify the production of excited fermions and bosons focussing on spin properties. The detailed of the contact interactions and the spin of the excited fermions and bosons can give important clues on the basic preon structure and dynamics. Phenomenological studies show that polarization asymmetries and angular distributions of decay products probe most sensitively the chiral properties of contact interactions and the spin of new states. Thus, polarized beams and good angular coverage are of great advantage

Synthesis of Biotin Linkers with the Activated Triple Bond Donor [p-(N-propynoylaminotoluic Acid] (PATA for Efficient Biotinylation of Peptides and Oligonucleotides

Directory of Open Access Journals (Sweden)

Martina Jezowska

2012-11-01

Full Text Available Biotin is an important molecule for modern biological studies including, e.g., cellular transport. Its exclusive affinity to fluorescent streptavidin/avidin proteins allows ready and specific detection. As a consequence methods for the attachment of biotin to various biological targets are of high importance, especially when they are very selective and can also proceed in water. One useful method is Hüisgen dipolar [3+2]-cycloaddition, commonly referred to as “click chemistry”. As we reported recently, the activated triple bond donor p-(N-propynoylaminotoluic acid (PATA gives excellent results when used for conjugations at submicromolar concentrations. Thus, we have designed and synthesized two biotin linkers, with different lengths equipped with this activated triple bond donor and we proceeded with biotinylation of oligonucleotides and C-myc peptide both in solution and on solid support with excellent yields of conversion.

Effective generation of transgenic pigs and mice by linker based sperm-mediated gene transfer.

Directory of Open Access Journals (Sweden)

Shih Ping Yao

2002-04-01

Full Text Available Abstract Background Transgenic animals have become valuable tools for both research and applied purposes. The current method of gene transfer, microinjection, which is widely used in transgenic mouse production, has only had limited success in producing transgenic animals of larger or higher species. Here, we report a linker based sperm-mediated gene transfer method (LB-SMGT that greatly improves the production efficiency of large transgenic animals. Results The linker protein, a monoclonal antibody (mAb C, is reactive to a surface antigen on sperm of all tested species including pig, mouse, chicken, cow, goat, sheep, and human. mAb C is a basic protein that binds to DNA through ionic interaction allowing exogenous DNA to be linked specifically to sperm. After fertilization of the egg, the DNA is shown to be successfully integrated into the genome of viable pig and mouse offspring with germ-line transfer to the F1 generation at a highly efficient rate: 37.5% of pigs and 33% of mice. The integration is demonstrated again by FISH analysis and F2 transmission in pigs. Furthermore, expression of the transgene is demonstrated in 61% (35/57 of transgenic pigs (F0 generation. Conclusions Our data suggests that LB-SMGT could be used to generate transgenic animals efficiently in many different species.

Prediction of the vibroacoustic behavior of a submerged shell with non-axisymmetric internal substructures by a condensed transfer function method

Science.gov (United States)

Meyer, V.; Maxit, L.; Guyader, J.-L.; Leissing, T.

2016-01-01

The vibroacoustic behavior of axisymmetric stiffened shells immersed in water has been intensively studied in the past. On the contrary, little attention has been paid to the modeling of these shells coupled to non-axisymmetric internal frames. Indeed, breaking the axisymmetry couples the circumferential orders of the Fourier series and considerably increases the computational costs. In order to tackle this issue, we propose a sub-structuring approach called the Condensed Transfer Function (CTF) method that will allow assembling a model of axisymmetric stiffened shell with models of non-axisymmetric internal frames. The CTF method is developed in the general case of mechanical subsystems coupled along curves. A set of orthonormal functions called condensation functions, which depend on the curvilinear abscissa along the coupling line, is considered. This set is then used as a basis for approximating and decomposing the displacements and the applied forces at the line junctions. Thanks to the definition and calculation of condensed transfer functions for each uncoupled subsystem and by using the superposition principle for passive linear systems, the behavior of the coupled subsystems can be deduced. A plane plate is considered as a test case to study the convergence of the method with respect to the type and the number of condensation functions taken into account. The CTF method is then applied to couple a submerged non-periodically stiffened shell described using the Circumferential Admittance Approach (CAA) with internal substructures described by Finite Element Method (FEM). The influence of non-axisymmetric internal substructures can finally be studied and it is shown that it tends to increase the radiation efficiency of the shell and can modify the vibrational and acoustic energy distribution.

Tidal stripping stellar substructures around four metal-poor globular clusters in the galactic bulge

International Nuclear Information System (INIS)

Chun, Sang-Hyun; Kang, Minhee; Jung, DooSeok; Sohn, Young-Jong

2015-01-01

We investigate the spatial density configuration of stars around four metal-poor globular clusters (NGC 6266, NGC 6626, NGC 6642, and NGC 6723) in the Galactic bulge region using wide-field deep J, H, and K imaging data obtained with the Wide Field Camera near-infrared array on the United Kingdom Infrared Telescope. A statistical weighted filtering algorithm for the stars on the color–magnitude diagram is applied in order to sort cluster member candidates from the field star contamination. In two-dimensional isodensity contour maps of the clusters, we find that all four of the globular clusters exhibit strong evidence of tidally stripped stellar features beyond the tidal radius in the form of tidal tails or small density lobes/chunks. The orientations of the extended stellar substructures are likely to be associated with the effect of dynamic interaction with the Galaxy and the cluster's space motion. The observed radial density profiles of the four globular clusters also describe the extended substructures; they depart from theoretical King and Wilson models and have an overdensity feature with a break in the slope of the profile at the outer region of clusters. The observed results could imply that four globular clusters in the Galactic bulge region have experienced strong environmental effects such as tidal forces or bulge/disk shocks of the Galaxy during the dynamical evolution of globular clusters. These observational results provide further details which add to our understanding of the evolution of clusters in the Galactic bulge region as well as the formation of the Galaxy.

Solving the Mystery of Galaxy Bulges and Bulge Substructure

Science.gov (United States)

Erwin, Peter

2017-08-01

Understanding galaxy bulges is crucial for understanding galaxy evolution and the growth of supermassive black holes (SMBHs). Recent studies have shown that at least some - perhaps most - disk-galaxy bulges are actually composite structures, with both classical-bulge (spheroid) and pseudobulge (disky) components; this calls into question the standard practice of using simple, low-resolution bulge/disk decompositions to determine spheroid and SMBH mass functions. We propose WFC3 optical and near-IR imaging of a volume- and mass-limited sample of local disk galaxies to determine the full range of pure-classical, pure-pseudobulge, and composite-bulge frequencies and parameters, including stellar masses for classical bulges, disky pseudobulges, and boxy/peanut-shaped bulges. We will combine this with ground-based spectroscopy to determine the stellar-kinematic and population characteristics of the different substructures revealed by our WFC3 imaging. This will help resolve growing uncertainties about the status and nature of bulges and their relation to SMBH masses, and will provide an essential local-universe reference for understanding bulge (and SMBH) formation and evolution.

A Dual-Purpose Linker for Alpha Helix Stabilization and Imaging Agent Conjugation to Glucagon-Like Peptide-1 Receptor Ligands

Science.gov (United States)

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

2016-01-01

Peptides display many characteristics of efficient imaging agents such as rapid targeting, fast background clearance, and low non-specific cellular uptake. However, poor stability, low affinity, and loss of binding after labeling often preclude their use in vivo. Using the glucagon-like peptide-1 receptor (GLP-1R) ligands exendin and GLP-1 as a model system, we designed a novel alpha helix stabilizing linker to simultaneously address these limitations. The stabilized and labeled peptides showed an increase in helicity, improved protease resistance, negligible loss or an improvement in binding affinity, and excellent in vivo targeting. The ease of incorporating azidohomoalanine in peptides and efficient reaction with the dialkyne linker enables this technique to potentially be used as a general method for labeling alpha helices. This strategy should be useful for imaging beta cells in diabetes research and in developing and testing other peptide targeting agents. PMID:25594741

SPECTROSCOPIC OBSERVATIONS OF AN EVOLVING FLARE RIBBON SUBSTRUCTURE SUGGESTING ORIGIN IN CURRENT SHEET WAVES

Energy Technology Data Exchange (ETDEWEB)

Brannon, S. R.; Longcope, D. W.; Qiu, J. [Department of Physics, Montana State University, Bozeman, MT 59717 (United States)

2015-09-01

We present imaging and spectroscopic observations from the Interface Region Imaging Spectrograph of the evolution of the flare ribbon in the SOL2014-04-18T13:03 M-class flare event, at high spatial resolution and time cadence. These observations reveal small-scale substructure within the ribbon, which manifests as coherent quasi-periodic oscillations in both position and Doppler velocities. We consider various alternative explanations for these oscillations, including modulation of chromospheric evaporation flows. Among these, we find the best support for some form of wave localized to the coronal current sheet, such as a tearing mode or Kelvin–Helmholtz instability.

Crystal substructures of the rotation-twinned T (Al20Cu2Mn3) phase in 2024 aluminum alloy

International Nuclear Information System (INIS)

Feng, Z.Q.; Yang, Y.Q.; Huang, B.; Li, M.H.; Chen, Y.X.; Ru, J.G.

2014-01-01

Highlights: • The substructures in rotation-twinned T (Al 20 Cu 2 Mn 3 ) particles were investigated. • A flattened hexagonal structural subunit with 20 atomic columns was proposed. • The stacking mode of these subunits at APB and TB were revealed. • The transition structures at twin domain junctions were unraveled. -- Abstract: The substructures in rotation-twinned T (Al 20 Cu 2 Mn 3 ) particles were investigated by means of high resolution transmission electron microscopy (HRTEM) and high angle annular dark field scanning transmission electron microscopy (HAADF-STEM) in the present work. A flattened hexagonal structural subunit with 20 atomic columns was proposed. The stacking mode of these subunits in non-defective T phase was proved to be tessellation of many flattened hexagonal subunits with the same orientations, while the stacking modes near anti-phase boundary (APB) and twin boundary (TB) were tessellations of two differently oriented flattened hexagonal subunits. The transition region at twin domain junctions has hybrid structure and perfect or imperfect pentagram structure. Centered with the perfect pentagram transition structure, a rotation twin with ten fan-shaped domains and constituted by five twin variants can be deduced

European Population Genetic Substructure: Further Definition of Ancestry Informative Markers for Distinguishing Among Diverse European Ethnic Groups

Science.gov (United States)

Tian, Chao; Kosoy, Roman; Nassir, Rami; Lee, Annette; Villoslada, Pablo; Klareskog, Lars; Hammarström, Lennart; Garchon, Henri-Jean; Pulver, Ann E.; Ransom, Michael; Gregersen, Peter K.; Seldin, Michael F.

2009-01-01

The definition of European population genetic substructure and its application to understanding complex phenotypes is becoming increasingly important. In the current study using over 4000 subjects genotyped for 300 thousand SNPs we provide further insight into relationships among European population groups and identify sets of SNP ancestry informative markers (AIMs) for application in genetic studies. In general, the graphical description of these principal components analyses (PCA) of diverse European subjects showed a strong correspondence to the geographical relationships of specific countries or regions of origin. Clearer separation of different ethnic and regional populations was observed when northern and southern European groups were considered separately and the PCA results were influenced by the inclusion or exclusion of different self-identified population groups including Ashkenazi Jewish, Sardinian and Orcadian ethnic groups. SNP AIM sets were identified that could distinguish the regional and ethnic population groups. Moreover, the studies demonstrated that most allele frequency differences between different European groups could be effectively controlled in analyses using these AIM sets. The European substructure AIMs should be widely applicable to ongoing studies to confirm and delineate specific disease susceptibility candidate regions without the necessity to perform additional genome-wide SNP studies in additional subject sets. PMID:19707526

Jet substructure and probes of CP violation in Vh production

Energy Technology Data Exchange (ETDEWEB)

Godbole, R.M. [Centre for High Energy Physics, Indian Institute of Science,Sir C.V. Raman Road, Bangalore 560012 (India); Miller, D.J. [School of Physics and Astronomy, Scottish Universities Physics Alliance, University of Glasgow,University Avenue, Glasgow G12 8QQ, Scotland (United Kingdom); Mohan, K.A. [Centre for High Energy Physics, Indian Institute of Science,Sir C.V. Raman Road, Bangalore 560012 (India); White, C.D. [School of Physics and Astronomy, Scottish Universities Physics Alliance, University of Glasgow,University Avenue, Glasgow G12 8QQ, Scotland (United Kingdom)

2015-04-20

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.

Mechanistic Evaluation of Motion in Redox-Driven Rotaxanes Reveals Longer Linkers Hasten Forward Escape's and Hinder Backward Translations

DEFF Research Database (Denmark)

Andersen, S. S.; Share, A. I.; Poulsen, B. L.

2014-01-01

temperatures to provide activation enthalpies (Delta H-double dagger) and entropies (Delta S-double dagger). Longer glycol linkers led to modest increases in the forward escape (t(1/2) = 60 to 69 s); though not because of a diffusive walk. The reduced rate of motion backward depended on folded structures...

Search for vector-like T' quarks using tools for the analysis of jet substructure with the CMS experiment

International Nuclear Information System (INIS)

Hoeing, Rebekka Sophie

2015-01-01

A search for pairs of vector-like T' quark produced in proton-proton collisions recorded with the CMS experiment at √(s)=8 TeV is presented. The search is optimized for decays of T' quarks to top quarks and Higgs bosons, where the top quarks and Higgs bosons decay hadronically. The T'-quark mass range between 500 and 1000 GeV is investigated. The top quarks and Higgs bosons produced in decays of the heavy T' quarks acquire large Lorentz boosts. The signatures of these particles in the detector can overlap and are therefore difficult to resolve using classical jet reconstruction methods. Large-radius jets are reconstructed and subjets formed from their constituents. The decay products of particles with large Lorentz boosts are highly collimated and can all be found within a single one of these large-radius jets. Top jets containing hadronic top-quark decays are identified with a top-tagging algorithm that analyzes the jet substructure. A b-tagging algorithm is applied to the reconstructed subjets in order to find bottom quarks within the jet substructure. In order to identify Higgs bosons with large Lorentz boosts decaying to pairs of bottom quarks, the Higgs-tagging algorithm searches for two b-tagged subjets within a single jet. This is the first application of a top-tagging algorithm in conjunction with subjet b-tagging in an analysis of CMS data. Also, a Higgs-tagging algorithm is used for the first time in a search for new physics. The main background contributions to this analysis consist of pair-produced top quarks and QCD-multijet events. More than 99% of these events are rejected by the event selection based on the new jet-substructure methods, while 6-8% of the signal events are retained. A description for the QCD-multijet background is obtained from data in a method also using jet-substructure information. Bayesian exclusion limits are derived from a likelihood ratio in which two discriminating variables are combined. T' quarks

Measurement of jet substructure observables in $\\mathrm{t \\bar t}$ events from pp collisions at $\\sqrt{s}=13~\\mathrm{TeV}$

CERN Document Server

CMS Collaboration

2018-01-01

A measurement of differential jet substructure observables is presented using $\\mathrm{t \\bar t}$ lepton+jets events from proton-proton collisions at $\\sqrt{s}=13~\\mathrm{TeV}$ recorded by the CMS experiment at the LHC in 2016 corresponding to an integrated luminosity of $35.9~\\mathrm{fb^{-1}}$. Multiple jet substructure variables, such as the particle multiplicity, width, eccentricity, $p_\\mathrm{T}$ dispersion, N-subjettiness ratios, generalized angularities, and energy correlation functions, are measured for inclusive jets, as well as for identified bottom, light-quark, and gluon jets from the $\\mathrm{t \\bar t}$ final state. The results are unfolded to the stable-particle level and compared to predictions from POWHEG interfaced with PYTHIA 8 and HERWIG 7.1, as well as from SHERPA 2 and DIRE. A reasonable agreement between the data and the Monte Carlo predictions is found. From a comparison of the jet width distribution to the prediction, it is shown that a lower value of the effective strong coupling in t...

Butane-1,2,3,4-tetraol-based amphiphilic stereoisomers for membrane protein study: importance of chirality in the linker region

DEFF Research Database (Denmark)

Das, Manabendra; Du, Yang; Mortensen, Jonas S.

2017-01-01

of the targeted membrane proteins depending on the chirality of the linker region. These findings indicate an important role for detergent stereochemistry in membrane protein stabilization. In addition, we generally observed enhanced detergent efficacy with increasing alkyl chain length, reinforcing...

Structural basis for activation of ZAP-70 by phosphorylation of the SH2-kinase linker.

Science.gov (United States)

Yan, Qingrong; Barros, Tiago; Visperas, Patrick R; Deindl, Sebastian; Kadlecek, Theresa A; Weiss, Arthur; Kuriyan, John

2013-06-01

Serial activation of the tyrosine kinases Lck and ZAP-70 initiates signaling downstream of the T cell receptor. We previously reported the structure of an autoinhibited ZAP-70 variant in which two regulatory tyrosine residues (315 and 319) in the SH2-kinase linker were replaced by phenylalanine. We now present a crystal structure of ZAP-70 in which Tyr 315 and Tyr 319 are not mutated, leading to the recognition of a five-residue sequence register error in the SH2-kinase linker of the original crystallographic model. The revised model identifies distinct roles for these two tyrosines. As seen in a recently reported structure of the related tyrosine kinase Syk, Tyr 315 of ZAP-70 is part of a hydrophobic interface between the regulatory apparatus and the kinase domain, and the integrity of this interface would be lost upon engagement of doubly phosphorylated peptides by the SH2 domains. Tyr 319 is not necessarily dislodged by SH2 engagement, which activates ZAP-70 only ∼5-fold in vitro. In contrast, phosphorylation by Lck activates ZAP-70 ∼100-fold. This difference is due to the ability of Tyr 319 to suppress ZAP-70 activity even when the SH2 domains are dislodged from the kinase domain, providing stringent control of ZAP-70 activity downstream of Lck.

Improving the performance of DomainDiscovery of protein domain boundary assignment using inter-domain linker index

Directory of Open Access Journals (Sweden)

Zomaya Albert Y

2006-12-01

Full Text Available Abstract Background Knowledge of protein domain boundaries is critical for the characterisation and understanding of protein function. The ability to identify domains without the knowledge of the structure – by using sequence information only – is an essential step in many types of protein analyses. In this present study, we demonstrate that the performance of DomainDiscovery is improved significantly by including the inter-domain linker index value for domain identification from sequence-based information. Improved DomainDiscovery uses a Support Vector Machine (SVM approach and a unique training dataset built on the principle of consensus among experts in defining domains in protein structure. The SVM was trained using a PSSM (Position Specific Scoring Matrix, secondary structure, solvent accessibility information and inter-domain linker index to detect possible domain boundaries for a target sequence. Results Improved DomainDiscovery is compared with other methods by benchmarking against a structurally non-redundant dataset and also CASP5 targets. Improved DomainDiscovery achieves 70% accuracy for domain boundary identification in multi-domains proteins. Conclusion Improved DomainDiscovery compares favourably to the performance of other methods and excels in the identification of domain boundaries for multi-domain proteins as a result of introducing support vector machine with benchmark_2 dataset.

In silico prediction of Tetrahymena pyriformis toxicity for diverse industrial chemicals with substructure pattern recognition and machine learning methods.

Science.gov (United States)

Cheng, Feixiong; Shen, Jie; Yu, Yue; Li, Weihua; Liu, Guixia; Lee, Philip W; Tang, Yun

2011-03-01

There is an increasing need for the rapid safety assessment of chemicals by both industries and regulatory agencies throughout the world. In silico techniques are practical alternatives in the environmental hazard assessment. It is especially true to address the persistence, bioaccumulative and toxicity potentials of organic chemicals. Tetrahymena pyriformis toxicity is often used as a toxic endpoint. In this study, 1571 diverse unique chemicals were collected from the literature and composed of the largest diverse data set for T. pyriformis toxicity. Classification predictive models of T. pyriformis toxicity were developed by substructure pattern recognition and different machine learning methods, including support vector machine (SVM), C4.5 decision tree, k-nearest neighbors and random forest. The results of a 5-fold cross-validation showed that the SVM method performed better than other algorithms. The overall predictive accuracies of the SVM classification model with radial basis functions kernel was 92.2% for the 5-fold cross-validation and 92.6% for the external validation set, respectively. Furthermore, several representative substructure patterns for characterizing T. pyriformis toxicity were also identified via the information gain analysis methods. Copyright © 2010 Elsevier Ltd. All rights reserved.

Lymphatic transport and lymph node targeting of methotrexate-conjugated PEGylated dendrimers are enhanced by reducing the length of the drug linker or masking interactions with the injection site.

Science.gov (United States)

Ryan, Gemma M; McLeod, Victoria M; Mehta, Dharmini; Kelly, Brian D; Stanislawski, Pauline C; Owen, David J; Kaminskas, Lisa M; Porter, Christopher J H

2017-11-01

Drug conjugation to dendrimer-based delivery systems has been shown to enhance delivery to the lymphatic system after subcutaneous administration. Dendrimer interaction with components of the interstitium at the injection site, however, may prevent drainage from the injection site. The current study sought to vary the length of a linker employed to conjugate methotrexate (MTX) to a PEGylated dendrimer, in an attempt to reduce MTX interaction with interstitial binding sites and enhance lymphatic drainage. Dendrimers with shorter linkers resulted in higher lymphatic drainage, presumably via shielding of interaction sites by the PEG mantle, but were not retained in lymph nodes. Improved drainage of dendrimers with longer linkers was achieved through coadministration with dextran to mask interactions at the injection site while maintaining retention within the node. Enhanced drug exposure to the lymph node has the potential to enhance the treatment of lymph-node resident cancer metastases. Copyright © 2017 Elsevier Inc. All rights reserved.

Microencapsulation of Epoxidized Linseed Oil Liquid Cross-Linker in Poly(N-vinyl-pyrrolidone): Optimization by a Design-of-Experiments Approach

NARCIS (Netherlands)

Senatore, D.; Laven, J.; Benthem, van R.A.T.M.; La Camera, D.; With, de G.

2010-01-01

A liquid cross-linker, epoxidized linseed oil (ELO), was encapsulated in a plastic with a high glass transition temperature (poly(N-vinyl-2-pyrrolidone); PVP). The process parameters of the spray-drying employed were optimized by a Design-of-Experiments (DoE) approach. Three factors concerning both

The ortho backbone amide linker (o-BAL) is an easily prepared and highly acid-labile handle for solid-phase synthesis

DEFF Research Database (Denmark)

Boas, Ulrik; Brask, Jesper; Christensen, J.B.

2002-01-01

The tris(alkoxy)benzyl backbone amide linker (BAL) has found widespread application in solid-phase synthesis. The key intermediate for preparation of para BAL (p-BAL) is 2,6-dimethoxy-4-hydroxybenzaldehyde; several reports on its synthesis have appeared. However, the ortho analogue of the handle (o...

Morphology and substructure of lath martensites in dilute Zr--Nb alloys

International Nuclear Information System (INIS)

Srivastava, D.; Mukhopadhyay, P.; Banerjee, S.

2000-01-01

The morphology and substructure of lath martensites formed in β quenched dilute Zr--Nb alloys are described. The laths are arranged in a nearly parallel manner within any given colony or packet. Packets of alternately twin related laths and clusters of three mutually twin related lath martensite variants have been observed and the twinning plane is of {1 anti 101} H type. With increasing niobium content a continuous transition from large colonies of lath martensites, through smaller lath colonies, to individual plates of the acicular martensites occurs. The lath-lath interface consists of regularly spaced parallel arrays of dislocations of type. The habit plane traces of lath martensite lie close to {334} type poles and the operating lattice invariant shear mode is { anti 1101} H H shear system. This result is consistent with results predicted by the phenomenological theory. The preferred two and three habit plane variant grouping clustering is explained on the basis of self-accommodation effects. (orig.)

The C. elegans tailless/Tlx homolog nhr-67 regulates a stage-specific program of linker cell migration in male gonadogenesis.

Science.gov (United States)

Kato, Mihoko; Sternberg, Paul W

2009-12-01

Cell migration is a common event during organogenesis, yet little is known about how migration is temporally coordinated with organ development. We are investigating stage-specific programs of cell migration using the linker cell (LC), a migratory cell crucial for male gonadogenesis of C. elegans. During the L3 and L4 larval stages of wild-type males, the LC undergoes changes in its position along the migratory route, in transcriptional regulation of the unc-5 netrin receptor and zmp-1 zinc matrix metalloprotease, and in cell morphology. We have identified the tailless homolog nhr-67 as a cell-autonomous, stage-specific regulator of timing in LC migration programs. In nhr-67-deficient animals, each of the L3 and L4 stage changes is either severely delayed or never occurs, yet LC development before the early L3 stage or after the mid-L4 stage occurs with normal timing. We propose that there is a basal migration program utilized throughout LC migration that is modified by stage-specific regulators such as nhr-67.

RESONANT CLUMPING AND SUBSTRUCTURE IN GALACTIC DISKS

International Nuclear Information System (INIS)

Molloy, Matthew; Smith, Martin C.; Shen, Juntai; Evans, N. Wyn

2015-01-01

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

RESONANT CLUMPING AND SUBSTRUCTURE IN GALACTIC DISKS

Energy Technology Data Exchange (ETDEWEB)

Molloy, Matthew [Kavli Institute for Astronomy and Astrophysics, Peking University, Yi He Yuan Lu 5, Hai Dian Qu, Beijing 100871 (China); Smith, Martin C.; Shen, Juntai [Key Laboratory for Research in Galaxies and Cosmology, Shanghai Astronomical Observatory, Chinese Academy of Sciences, 80 Nandan Road, Shanghai 200030 (China); Evans, N. Wyn, E-mail: matthewmolloy@gmail.com, E-mail: msmith@shao.ac.cn, E-mail: jshen@shao.ac.cn, E-mail: nwe@ast.cam.ac.uk [Institute of Astronomy, Madingley Road, Cambridge, CB3 0HA (United Kingdom)

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.

Performance of jet substructure techniques for large-R jets in proton-proton collisions at $\\sqrt{s}$ = 7 TeV using the ATLAS detector

CERN Document Server

Aad, Georges; Abbott, Brad; Abdallah, Jalal; Abdel Khalek, Samah; Abdelalim, Ahmed Ali; Abdinov, Ovsat; Aben, Rosemarie; Abi, Babak; Abolins, Maris; AbouZeid, Ossama; Abramowicz, Halina; Abreu, Henso; Abulaiti, Yiming; Acharya, Bobby Samir; Adamczyk, Leszek; Adams, David; Addy, Tetteh; Adelman, Jahred; Adomeit, Stefanie; Adye, Tim; Aefsky, Scott; Aguilar-Saavedra, Juan Antonio; Agustoni, Marco; Ahlen, Steven; Ahles, Florian; Ahmad, Ashfaq; Ahsan, Mahsana; Aielli, Giulio; Åkesson, Torsten Paul Ake; Akimoto, Ginga; Akimov, Andrei; Alam, Muhammad Aftab; Albert, Justin; Albrand, Solveig; Aleksa, Martin; Aleksandrov, Igor; Alessandria, Franco; Alexa, Calin; Alexander, Gideon; Alexandre, Gauthier; Alexopoulos, Theodoros; Alhroob, Muhammad; Aliev, Malik; Alimonti, Gianluca; Alison, John; Allbrooke, Benedict; Allison, Lee John; Allport, Phillip; Allwood-Spiers, Sarah; Almond, John; Aloisio, Alberto; Alon, Raz; Alonso, Alejandro; Alonso, Francisco; Altheimer, Andrew David; Alvarez Gonzalez, Barbara; Alviggi, Mariagrazia; Amako, Katsuya; Amaral Coutinho, Yara; Amelung, Christoph; Ammosov, Vladimir; Amor Dos Santos, Susana Patricia; Amorim, Antonio; Amoroso, Simone; Amram, Nir; Anastopoulos, Christos; Ancu, Lucian Stefan; Andari, Nansi; Andeen, Timothy; Anders, Christoph Falk; Anders, Gabriel; Anderson, Kelby; Andreazza, Attilio; Andrei, George Victor; Anduaga, Xabier; Angelidakis, Stylianos; Anger, Philipp; Angerami, Aaron; Anghinolfi, Francis; Anisenkov, Alexey; Anjos, Nuno; Annovi, Alberto; Antonaki, Ariadni; Antonelli, Mario; Antonov, Alexey; Antos, Jaroslav; Anulli, Fabio; Aoki, Masato; Aperio Bella, Ludovica; Apolle, Rudi; Arabidze, Giorgi; Aracena, Ignacio; Arai, Yasuo; Arce, Ayana; Arfaoui, Samir; Arguin, Jean-Francois; Argyropoulos, Spyridon; Arik, Engin; Arik, Metin; Armbruster, Aaron James; Arnaez, Olivier; Arnal, Vanessa; Artamonov, Andrei; Artoni, Giacomo; Arutinov, David; Asai, Shoji; Asbah, Nedaa; Ask, Stefan; Åsman, Barbro; Asquith, Lily; Assamagan, Ketevi; Astalos, Robert; Astbury, Alan; Atkinson, Markus; Auerbach, Benjamin; Auge, Etienne; Augsten, Kamil; Aurousseau, Mathieu; Avolio, Giuseppe; Axen, David; Azuelos, Georges; Azuma, Yuya; Baak, Max; Baccaglioni, Giuseppe; Bacci, Cesare; Bach, Andre; Bachacou, Henri; Bachas, Konstantinos; Backes, Moritz; Backhaus, Malte; Backus Mayes, John; Badescu, Elisabeta; Bagiacchi, Paolo; Bagnaia, Paolo; Bai, Yu; Bailey, David; Bain, Travis; Baines, John; Baker, Oliver Keith; Baker, Sarah; Balek, Petr; Balli, Fabrice; Banas, Elzbieta; Banerjee, Piyali; Banerjee, Swagato; Banfi, Danilo; Bangert, Andrea Michelle; Bansal, Vikas; Bansil, Hardeep Singh; Barak, Liron; Baranov, Sergei; Barber, Tom; Barberio, Elisabetta Luigia; Barberis, Dario; Barbero, Marlon; Bardin, Dmitri; Barillari, Teresa; Barisonzi, Marcello; Barklow, Timothy; Barlow, Nick; Barnett, Bruce; Barnett, Michael; Baroncelli, Antonio; Barone, Gaetano; Barr, Alan; Barreiro, Fernando; Barreiro Guimarães da Costa, João; Bartoldus, Rainer; Barton, Adam Edward; Bartsch, Valeria; Basye, Austin; Bates, Richard; Batkova, Lucia; Batley, Richard; Battaglia, Andreas; Battistin, Michele; Bauer, Florian; Bawa, Harinder Singh; Beale, Steven; Beau, Tristan; Beauchemin, Pierre-Hugues; Beccherle, Roberto; Bechtle, Philip; Beck, Hans Peter; Becker, Anne Kathrin; Becker, Sebastian; Beckingham, Matthew; Becks, Karl-Heinz; Beddall, Andrew; Beddall, Ayda; Bedikian, Sourpouhi; Bednyakov, Vadim; Bee, Christopher; Beemster, Lars; Beermann, Thomas; Begel, Michael; Belanger-Champagne, Camille; Bell, Paul; Bell, William; Bella, Gideon; Bellagamba, Lorenzo; Bellerive, Alain; Bellomo, Massimiliano; Belloni, Alberto; Beloborodova, Olga; Belotskiy, Konstantin; Beltramello, Olga; Benary, Odette; Benchekroun, Driss; Bendtz, Katarina; Benekos, Nektarios; Benhammou, Yan; Benhar Noccioli, Eleonora; Benitez Garcia, Jorge-Armando; Benjamin, Douglas; Bensinger, James; Benslama, Kamal; Bentvelsen, Stan; Berge, David; Bergeaas Kuutmann, Elin; Berger, Nicolas; Berghaus, Frank; Berglund, Elina; Beringer, Jürg; Bernat, Pauline; Bernhard, Ralf; Bernius, Catrin; Bernlochner, Florian Urs; Berry, Tracey; Bertella, Claudia; Bertolucci, Federico; Besana, Maria Ilaria; Besjes, Geert-Jan; Besson, Nathalie; Bethke, Siegfried; Bhimji, Wahid; Bianchi, Riccardo-Maria; Bianchini, Louis; Bianco, Michele; Biebel, Otmar; Bieniek, Stephen Paul; Bierwagen, Katharina; Biesiada, Jed; Biglietti, Michela; Bilokon, Halina; Bindi, Marcello; Binet, Sebastien; Bingul, Ahmet; Bini, Cesare; Bittner, Bernhard; Black, Curtis; Black, James; Black, Kevin; Blair, Robert; Blanchard, Jean-Baptiste; Blazek, Tomas; Bloch, Ingo; Blocker, Craig; Blocki, Jacek; Blum, Walter; Blumenschein, Ulrike; Bobbink, Gerjan; Bobrovnikov, Victor; Bocchetta, Simona Serena; Bocci, Andrea; Boddy, Christopher Richard; Boehler, Michael; Boek, Jennifer; Boek, Thorsten Tobias; Boelaert, Nele; Bogaerts, Joannes Andreas; Bogdanchikov, Alexander; Bogouch, Andrei; Bohm, Christian; Bohm, Jan; Boisvert, Veronique; Bold, Tomasz; Boldea, Venera; Bolnet, Nayanka Myriam; Bomben, Marco; Bona, Marcella; Boonekamp, Maarten; Bordoni, Stefania; Borer, Claudia; Borisov, Anatoly; Borissov, Guennadi; Borri, Marcello; Borroni, Sara; Bortfeldt, Jonathan; Bortolotto, Valerio; Bos, Kors; Boscherini, Davide; Bosman, Martine; Boterenbrood, Hendrik; Bouchami, Jihene; Boudreau, Joseph; Bouhova-Thacker, Evelina Vassileva; Boumediene, Djamel Eddine; Bourdarios, Claire; Bousson, Nicolas; Boutouil, Sara; Boveia, Antonio; Boyd, James; Boyko, Igor; Bozovic-Jelisavcic, Ivanka; Bracinik, Juraj; Branchini, Paolo; Brandt, Andrew; Brandt, Gerhard; Brandt, Oleg; Bratzler, Uwe; Brau, Benjamin; Brau, James; Braun, Helmut; Brazzale, Simone Federico; Brelier, Bertrand; Bremer, Johan; Brendlinger, Kurt; Brenner, Richard; Bressler, Shikma; Bristow, Timothy Michael; Britton, Dave; Brochu, Frederic; Brock, Ian; Brock, Raymond; Broggi, Francesco; Bromberg, Carl; Bronner, Johanna; Brooijmans, Gustaaf; Brooks, Timothy; Brooks, William; Brown, Gareth; Bruckman de Renstrom, Pawel; Bruncko, Dusan; 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Charlton, Dave; Chavda, Vikash; Chavez Barajas, Carlos Alberto; Cheatham, Susan; Chekanov, Sergei; Chekulaev, Sergey; Chelkov, Gueorgui; Chelstowska, Magda Anna; Chen, Chunhui; Chen, Hucheng; Chen, Shenjian; Chen, Xin; Chen, Yujiao; Cheng, Yangyang; Cheplakov, Alexander; Cherkaoui El Moursli, Rajaa; Chernyatin, Valeriy; Cheu, Elliott; Cheung, Sing-Leung; Chevalier, Laurent; Chiarella, Vitaliano; Chiefari, Giovanni; Childers, John Taylor; Chilingarov, Alexandre; Chiodini, Gabriele; Chisholm, Andrew; Chislett, Rebecca Thalatta; Chitan, Adrian; Chizhov, Mihail; Choudalakis, Georgios; Chouridou, Sofia; Chow, Bonnie Kar Bo; Christidi, Ilektra-Athanasia; Christov, Asen; Chromek-Burckhart, Doris; Chu, Ming-Lee; Chudoba, Jiri; Ciapetti, Guido; Ciftci, Abbas Kenan; Ciftci, Rena; Cinca, Diane; Cindro, Vladimir; Ciocio, Alessandra; Cirilli, Manuela; Cirkovic, Predrag; Citron, Zvi Hirsh; Citterio, Mauro; Ciubancan, Mihai; Clark, Allan G; Clark, Philip James; Clarke, Robert; Clemens, Jean-Claude; Clement, Benoit; 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Cuhadar Donszelmann, Tulay; Cummings, Jane; Curatolo, Maria; Curtis, Chris; Cuthbert, Cameron; Czirr, Hendrik; Czodrowski, Patrick; Czyczula, Zofia; D'Auria, Saverio; D'Onofrio, Monica; D'Orazio, Alessia; Da Cunha Sargedas De Sousa, Mario Jose; Da Via, Cinzia; Dabrowski, Wladyslaw; Dafinca, Alexandru; Dai, Tiesheng; Dallaire, Frederick; Dallapiccola, Carlo; Dam, Mogens; Damiani, Daniel; Daniells, Andrew Christopher; Danielsson, Hans Olof; Dao, Valerio; Darbo, Giovanni; Darlea, Georgiana Lavinia; Darmora, Smita; Dassoulas, James; Davey, Will; Davidek, Tomas; Davidson, Nadia; Davies, Eleanor; Davies, Merlin; Davignon, Olivier; Davison, Adam; Davygora, Yuriy; Dawe, Edmund; Dawson, Ian; Daya-Ishmukhametova, Rozmin; De, Kaushik; de Asmundis, Riccardo; De Castro, Stefano; De Cecco, Sandro; de Graat, Julien; De Groot, Nicolo; de Jong, Paul; De La Taille, Christophe; De la Torre, Hector; De Lorenzi, Francesco; De Nooij, Lucie; De Pedis, Daniele; De Salvo, Alessandro; De Sanctis, Umberto; De Santo, Antonella; De Vivie De Regie, Jean-Baptiste; De Zorzi, Guido; Dearnaley, William James; Debbe, Ramiro; Debenedetti, Chiara; Dechenaux, Benjamin; Dedovich, Dmitri; Degenhardt, James; Del Peso, Jose; Del Prete, Tarcisio; Delemontex, Thomas; Deliyergiyev, Maksym; Dell'Acqua, Andrea; Dell'Asta, Lidia; Della Pietra, Massimo; della Volpe, Domenico; Delmastro, Marco; Delsart, Pierre-Antoine; Deluca, Carolina; Demers, Sarah; Demichev, Mikhail; Demilly, Aurelien; Demirkoz, Bilge; Denisov, Sergey; Derendarz, Dominik; Derkaoui, Jamal Eddine; Derue, Frederic; Dervan, Paul; Desch, Klaus Kurt; Deviveiros, Pier-Olivier; Dewhurst, Alastair; DeWilde, Burton; Dhaliwal, Saminder; Dhullipudi, Ramasudhakar; Di Ciaccio, Anna; Di Ciaccio, Lucia; Di Donato, Camilla; Di Girolamo, Alessandro; Di Girolamo, Beniamino; Di Luise, Silvestro; Di Mattia, Alessandro; Di Micco, Biagio; Di Nardo, Roberto; Di Simone, Andrea; Di Sipio, Riccardo; Diaz, Marco Aurelio; Diehl, Edward; Dietrich, Janet; Dietzsch, Thorsten; Diglio, Sara; Dindar Yagci, Kamile; 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Ellert, Mattias; Elles, Sabine; Ellinghaus, Frank; Ellis, Katherine; Ellis, Nicolas; Elmsheuser, Johannes; Elsing, Markus; Emeliyanov, Dmitry; Enari, Yuji; Endner, Oliver Chris; Engelmann, Roderich; Engl, Albert; Erdmann, Johannes; Ereditato, Antonio; Eriksson, Daniel; Ernst, Jesse; Ernst, Michael; Ernwein, Jean; Errede, Deborah; Errede, Steven; Ertel, Eugen; Escalier, Marc; Esch, Hendrik; Escobar, Carlos; Espinal Curull, Xavier; Esposito, Bellisario; Etienne, Francois; Etienvre, Anne-Isabelle; Etzion, Erez; Evangelakou, Despoina; Evans, Hal; Fabbri, Laura; Fabre, Caroline; Facini, Gabriel; Fakhrutdinov, Rinat; Falciano, Speranza; Fang, Yaquan; Fanti, Marcello; Farbin, Amir; Farilla, Addolorata; Farooque, Trisha; Farrell, Steven; Farrington, Sinead; Farthouat, Philippe; Fassi, Farida; Fassnacht, Patrick; Fassouliotis, Dimitrios; Fatholahzadeh, Baharak; Favareto, Andrea; Fayard, Louis; Federic, Pavol; Fedin, Oleg; Fedorko, Wojciech; Fehling-Kaschek, Mirjam; Feligioni, Lorenzo; Feng, Cunfeng; Feng, Eric; Feng, Haolu; Fenyuk, Alexander; Ferencei, Jozef; Fernando, Waruna; Ferrag, Samir; Ferrando, James; Ferrara, Valentina; Ferrari, Arnaud; Ferrari, Pamela; Ferrari, Roberto; Ferreira de Lima, Danilo Enoque; Ferrer, Antonio; Ferrere, Didier; Ferretti, Claudio; Ferretto Parodi, Andrea; Fiascaris, Maria; Fiedler, Frank; Filipčič, Andrej; Filthaut, Frank; Fincke-Keeler, Margret; Finelli, Kevin Daniel; Fiolhais, Miguel; Fiorini, Luca; Firan, Ana; Fischer, Julia; Fisher, Matthew; Fitzgerald, Eric Andrew; Flechl, Martin; Fleck, Ivor; Fleischmann, Philipp; Fleischmann, Sebastian; Fletcher, Gareth Thomas; Fletcher, Gregory; Flick, Tobias; Floderus, Anders; Flores Castillo, Luis; Florez Bustos, Andres Carlos; Flowerdew, Michael; Fonseca Martin, Teresa; Formica, Andrea; Forti, Alessandra; Fortin, Dominique; Fournier, Daniel; Fox, Harald; Francavilla, Paolo; Franchini, Matteo; Franchino, Silvia; Francis, David; Franklin, Melissa; Franz, Sebastien; Fraternali, Marco; Fratina, Sasa; French, Sky; Friedrich, Conrad; Friedrich, Felix; Froidevaux, Daniel; Frost, James; Fukunaga, Chikara; Fullana Torregrosa, Esteban; Fulsom, Bryan Gregory; Fuster, Juan; Gabaldon, Carolina; Gabizon, Ofir; Gabrielli, Alessandro; Gabrielli, Andrea; Gadatsch, Stefan; Gadfort, Thomas; Gadomski, Szymon; Gagliardi, Guido; Gagnon, Pauline; Galea, Cristina; Galhardo, Bruno; Gallas, Elizabeth; Gallo, Valentina Santina; Gallop, Bruce; Gallus, Petr; Gan, KK; Gandrajula, Reddy Pratap; Gao, Yongsheng; Gaponenko, Andrei; Garay Walls, Francisca; Garberson, Ford; García, Carmen; García Navarro, José Enrique; Garcia-Sciveres, Maurice; Gardner, Robert; Garelli, Nicoletta; Garonne, Vincent; Gatti, Claudio; Gaudio, Gabriella; Gaur, Bakul; Gauthier, Lea; Gauzzi, Paolo; Gavrilenko, Igor; Gay, Colin; Gaycken, Goetz; Gazis, Evangelos; Ge, Peng; Gecse, Zoltan; Gee, Norman; Geerts, Daniël Alphonsus Adrianus; Geich-Gimbel, Christoph; Gellerstedt, Karl; Gemme, Claudia; Gemmell, Alistair; Genest, Marie-Hélène; Gentile, Simonetta; George, Matthias; George, Simon; Gerbaudo, Davide; Gershon, Avi; Ghazlane, Hamid; Ghodbane, Nabil; Giacobbe, Benedetto; Giagu, Stefano; Giangiobbe, Vincent; Gianotti, Fabiola; Gibbard, Bruce; Gibson, Adam; Gibson, Stephen; Gilchriese, Murdock; Gillam, Thomas; Gillberg, Dag; Gillman, Tony; Gingrich, Douglas; Giokaris, Nikos; Giordani, MarioPaolo; Giordano, Raffaele; Giorgi, Francesco Michelangelo; Giovannini, Paola; Giraud, Pierre-Francois; Giugni, Danilo; Giuliani, Claudia; Giunta, Michele; Gjelsten, Børge Kile; Gkialas, Ioannis; Gladilin, Leonid; Glasman, Claudia; Glatzer, Julian; Glazov, Alexandre; Glonti, George; Goddard, Jack Robert; Godfrey, Jennifer; Godlewski, Jan; Goebel, Martin; Goeringer, Christian; Goldfarb, Steven; Golling, Tobias; Golubkov, Dmitry; Gomes, Agostinho; Gomez Fajardo, Luz Stella; Gonçalo, Ricardo; Goncalves Pinto Firmino Da Costa, Joao; Gonella, Laura; González de la Hoz, Santiago; Gonzalez Parra, Garoe; Gonzalez Silva, Laura; Gonzalez-Sevilla, Sergio; Goodson, Jeremiah Jet; Goossens, Luc; Gorbounov, Petr Andreevich; Gordon, Howard; Gorelov, Igor; Gorfine, Grant; Gorini, Benedetto; Gorini, Edoardo; Gorišek, Andrej; Gornicki, Edward; Goshaw, Alfred; Gössling, Claus; Gostkin, Mikhail Ivanovitch; Gough Eschrich, Ivo; Gouighri, Mohamed; Goujdami, Driss; Goulette, Marc Phillippe; Goussiou, Anna; Goy, Corinne; Gozpinar, Serdar; Graber, Lars; Grabowska-Bold, Iwona; Grafström, Per; Grahn, Karl-Johan; Gramstad, Eirik; Grancagnolo, Francesco; Grancagnolo, Sergio; Grassi, Valerio; Gratchev, Vadim; Gray, Heather; Gray, Julia Ann; Graziani, Enrico; Grebenyuk, Oleg; Greenshaw, Timothy; Greenwood, Zeno Dixon; Gregersen, Kristian; Gregor, Ingrid-Maria; Grenier, Philippe; Griffiths, Justin; Grigalashvili, Nugzar; Grillo, Alexander; Grimm, Kathryn; Grinstein, Sebastian; Gris, Philippe Luc Yves; Grishkevich, Yaroslav; Grivaz, Jean-Francois; Grohs, Johannes Philipp; Grohsjean, Alexander; Gross, Eilam; Grosse-Knetter, Joern; Groth-Jensen, Jacob; Grybel, Kai; Guescini, Francesco; Guest, Daniel; Gueta, Orel; Guicheney, Christophe; Guido, Elisa; Guillemin, Thibault; Guindon, Stefan; Gul, Umar; Gunther, Jaroslav; Guo, Jun; Gutierrez, Phillip; Guttman, Nir; Gutzwiller, Olivier; Guyot, Claude; Gwenlan, Claire; Gwilliam, Carl; Haas, Andy; Haas, Stefan; Haber, Carl; Hadavand, Haleh Khani; Haefner, Petra; Hajduk, Zbigniew; Hakobyan, Hrachya; Hall, David; Halladjian, Garabed; Hamacher, Klaus; Hamal, Petr; Hamano, Kenji; Hamer, Matthias; Hamilton, Andrew; Hamilton, Samuel; Han, Liang; Hanagaki, Kazunori; Hanawa, Keita; Hance, Michael; Handel, Carsten; Hanke, Paul; Hansen, John Renner; Hansen, Jørgen Beck; Hansen, Jorn Dines; Hansen, Peter Henrik; Hansson, Per; Hara, Kazuhiko; Hard, Andrew; Harenberg, Torsten; Harkusha, Siarhei; Harper, Devin; Harrington, Robert; Harris, Orin; Hartert, Jochen; Hartjes, Fred; Haruyama, Tomiyoshi; Harvey, Alex; Hasegawa, Satoshi; Hasegawa, Yoji; Hassani, Samira; Haug, Sigve; Hauschild, Michael; Hauser, Reiner; Havranek, Miroslav; Hawkes, Christopher; Hawkings, Richard John; Hawkins, Anthony David; Hayakawa, Takashi; Hayashi, Takayasu; Hayden, Daniel; Hays, Chris; Hayward, Helen; Haywood, Stephen; Head, Simon; Heck, Tobias; Hedberg, Vincent; Heelan, Louise; Heim, Sarah; Heinemann, Beate; Heisterkamp, Simon; Hejbal, Jiri; Helary, Louis; Heller, Claudio; Heller, Matthieu; Hellman, Sten; Hellmich, Dennis; Helsens, Clement; Henderson, James; Henderson, Robert; Henke, Michael; Henrichs, Anna; Henriques Correia, Ana Maria; Henrot-Versille, Sophie; Hensel, Carsten; Herbert, Geoffrey Henry; Medina Hernandez, Carlos; Hernández Jiménez, Yesenia; Herrberg-Schubert, Ruth; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Hesketh, Gavin Grant; Hessey, Nigel; Hickling, Robert; Higón-Rodriguez, Emilio; Hill, John; Hiller, Karl Heinz; Hillert, Sonja; Hillier, Stephen; Hinchliffe, Ian; Hines, Elizabeth; Hirose, Minoru; Hirschbuehl, Dominic; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hodgson, Paul; Hoecker, Andreas; Hoeferkamp, Martin; Hoffman, Julia; Hoffmann, Dirk; Hofmann, Julia Isabell; Hohlfeld, Marc; Holmgren, Sven-Olof; Holzbauer, Jenny; Hong, Tae Min; Hooft van Huysduynen, Loek; Hostachy, Jean-Yves; Hou, Suen; Hoummada, Abdeslam; Howard, Jacob; Howarth, James; Hrabovsky, Miroslav; Hristova, Ivana; Hrivnac, Julius; Hryn'ova, Tetiana; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Hu, Diedi; Hu, Xueye; Hubacek, Zdenek; Hubaut, Fabrice; Huegging, Fabian; Huettmann, Antje; Huffman, Todd Brian; Hughes, Emlyn; Hughes, Gareth; Huhtinen, Mika; Hülsing, Tobias Alexander; Hurwitz, Martina; Huseynov, Nazim; Huston, Joey; Huth, John; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibragimov, Iskander; Iconomidou-Fayard, Lydia; Idarraga, John; Iengo, Paolo; Igonkina, Olga; Ikegami, Yoichi; Ikematsu, Katsumasa; Ikeno, Masahiro; Iliadis, Dimitrios; Ilic, Nikolina; Ince, Tayfun; Ioannou, Pavlos; Iodice, Mauro; Iordanidou, Kalliopi; Ippolito, Valerio; Irles Quiles, Adrian; Isaksson, Charlie; Ishino, Masaya; Ishitsuka, Masaki; Ishmukhametov, Renat; Issever, Cigdem; Istin, Serhat; Ivashin, Anton; Iwanski, Wieslaw; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jackson, Brett; Jackson, John; Jackson, Paul; Jaekel, Martin; Jain, Vivek; Jakobs, Karl; Jakobsen, Sune; Jakoubek, Tomas; Jakubek, Jan; Jamin, David Olivier; Jana, Dilip; Jansen, Eric; Jansen, Hendrik; Janssen, Jens; Jantsch, Andreas; Janus, Michel; Jared, Richard; Jarlskog, Göran; Jeanty, Laura; Jeng, Geng-yuan; Jen-La Plante, Imai; Jennens, David; Jenni, Peter; Jentzsch, Jennifer; Jeske, Carl; Jež, Pavel; Jézéquel, Stéphane; Jha, Manoj Kumar; Ji, Haoshuang; Ji, Weina; Jia, Jiangyong; Jiang, Yi; Jimenez Belenguer, Marcos; Jin, Shan; Jinnouchi, Osamu; Joergensen, Morten Dam; Joffe, David; Johansen, Marianne; Johansson, Erik; Johansson, Per; Johnert, Sebastian; Johns, Kenneth; Jon-And, Kerstin; Jones, Graham; Jones, Roger; Jones, Tim; Jorge, Pedro; Joshi, Kiran Daniel; Jovicevic, Jelena; Jovin, Tatjana; Ju, Xiangyang; Jung, Christian; Jungst, Ralph Markus; Jussel, Patrick; Juste Rozas, Aurelio; Kabana, Sonja; Kaci, Mohammed; Kaczmarska, Anna; Kadlecik, Peter; Kado, Marumi; Kagan, Harris; Kagan, Michael; Kajomovitz, Enrique; Kalinin, Sergey; Kama, Sami; Kanaya, Naoko; Kaneda, Michiru; Kaneti, Steven; Kanno, Takayuki; Kantserov, Vadim; Kanzaki, Junichi; Kaplan, Benjamin; Kapliy, Anton; Kar, Deepak; Karakostas, Konstantinos; Karnevskiy, Mikhail; Kartvelishvili, Vakhtang; Karyukhin, Andrey; Kashif, Lashkar; Kasieczka, Gregor; Kass, Richard; Kastanas, Alex; Kataoka, Yousuke; Katzy, Judith; Kaushik, Venkatesh; Kawagoe, Kiyotomo; Kawamoto, Tatsuo; Kawamura, Gen; Kazama, Shingo; Kazanin, Vassili; Kazarinov, Makhail; Keeler, Richard; Keener, Paul; Kehoe, Robert; Keil, Markus; Keller, John; Keoshkerian, Houry; Kepka, Oldrich; Kerševan, Borut Paul; Kersten, Susanne; Kessoku, Kohei; Keung, Justin; Khalil-zada, Farkhad; Khandanyan, Hovhannes; Khanov, Alexander; Kharchenko, Dmitri; Khodinov, Alexander; Khomich, Andrei; Khoo, Teng Jian; Khoriauli, Gia; Khoroshilov, Andrey; Khovanskiy, Valery; Khramov, Evgeniy; Khubua, Jemal; Kim, Hyeon Jin; Kim, Shinhong; Kimura, Naoki; Kind, Oliver; King, Barry; King, Matthew; King, Robert Steven Beaufoy; King, Samuel Burton; Kirk, Julie; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kitamura, Takumi; Kittelmann, Thomas; Kiuchi, Kenji; Kladiva, Eduard; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klemetti, Miika; Klier, Amit; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klinger, Joel Alexander; Klinkby, Esben; Klioutchnikova, Tatiana; Klok, Peter; Kluge, Eike-Erik; Kluit, Peter; Kluth, Stefan; Kneringer, Emmerich; Knoops, Edith; Knue, Andrea; Ko, Byeong Rok; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Koenig, Sebastian; Koetsveld, Folkert; Koevesarki, Peter; Koffas, Thomas; Koffeman, Els; Kogan, Lucy Anne; Kohlmann, Simon; Kohn, Fabian; Kohout, Zdenek; Kohriki, Takashi; Koi, Tatsumi; Kolanoski, Hermann; Koletsou, Iro; Koll, James; Komar, Aston; Komori, Yuto; Kondo, Takahiko; Köneke, Karsten; König, Adriaan; Kono, Takanori; Kononov, Anatoly; Konoplich, Rostislav; Konstantinidis, Nikolaos; Kopeliansky, Revital; Koperny, Stefan; Köpke, Lutz; Kopp, Anna Katharina; Korcyl, Krzysztof; Kordas, Kostantinos; Korn, Andreas; Korol, Aleksandr; Korolkov, Ilya; Korolkova, Elena; Korotkov, Vladislav; Kortner, Oliver; Kortner, Sandra; Kostyukhin, Vadim; Kotov, Sergey; Kotov, Vladislav; Kotwal, Ashutosh; Kourkoumelis, Christine; Kouskoura, Vasiliki; Koutsman, Alex; Kowalewski, Robert Victor; Kowalski, Tadeusz; Kozanecki, Witold; Kozhin, Anatoly; Kral, Vlastimil; Kramarenko, Viktor; Kramberger, Gregor; Krasny, Mieczyslaw Witold; Krasznahorkay, Attila; Kraus, Jana; Kravchenko, Anton; Kreiss, Sven; Kretzschmar, Jan; Kreutzfeldt, Kristof; Krieger, Nina; Krieger, Peter; Kroeninger, Kevin; Kroha, Hubert; Kroll, Joe; Kroseberg, Juergen; Krstic, Jelena; Kruchonak, Uladzimir; Krüger, Hans; Kruker, Tobias; Krumnack, Nils; Krumshteyn, Zinovii; Kruse, Amanda; Kruse, Mark; Kubota, Takashi; Kuday, Sinan; Kuehn, Susanne; Kugel, Andreas; Kuhl, Thorsten; Kukhtin, Victor; Kulchitsky, Yuri; Kuleshov, Sergey; Kuna, Marine; Kunkle, Joshua; Kupco, Alexander; Kurashige, Hisaya; Kurata, Masakazu; Kurochkin, Yurii; Kus, Vlastimil; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; Kwee, Regina; La Rosa, Alessandro; La Rotonda, Laura; Labarga, Luis; Lablak, Said; Lacasta, Carlos; Lacava, Francesco; Lacey, James; Lacker, Heiko; Lacour, Didier; Lacuesta, Vicente Ramón; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lagouri, Theodota; Lai, Stanley; Laier, Heiko; Laisne, Emmanuel; Lambourne, Luke; Lampen, Caleb; Lampl, Walter; Lançon, Eric; Landgraf, Ulrich; Landon, Murrough; Lang, Valerie Susanne; Lange, Clemens; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Lanza, Agostino; Laplace, Sandrine; Lapoire, Cecile; Laporte, Jean-Francois; Lari, Tommaso; Larner, Aimee; Lassnig, Mario; Laurelli, Paolo; Lavorini, Vincenzo; Lavrijsen, Wim; Laycock, Paul; Le Dortz, Olivier; Le Guirriec, Emmanuel; Le Menedeu, Eve; LeCompte, Thomas; Ledroit-Guillon, Fabienne Agnes Marie; Lee, Hurng-Chun; Lee, Jason; Lee, Shih-Chang; Lee, Lawrence; Lefebvre, Guillaume; Lefebvre, Michel; Legendre, Marie; Legger, Federica; Leggett, Charles; Lehmacher, Marc; Lehmann Miotto, Giovanna; Leister, Andrew Gerard; Leite, Marco Aurelio Lisboa; Leitner, Rupert; Lellouch, Daniel; Lemmer, Boris; Lendermann, Victor; Leney, Katharine; Lenz, Tatiana; Lenzen, Georg; Lenzi, Bruno; Leonhardt, Kathrin; Leontsinis, Stefanos; Lepold, Florian; Leroy, Claude; Lessard, Jean-Raphael; Lester, Christopher; Lester, Christopher Michael; Levêque, Jessica; Levin, Daniel; Levinson, Lorne; Lewis, Adrian; Lewis, George; Leyko, Agnieszka; Leyton, Michael; Li, Bing; Li, Bo; Li, Haifeng; Li, Ho Ling; Li, Shu; Li, Xuefei; Liang, Zhijun; Liao, Hongbo; Liberti, Barbara; Lichard, Peter; Lie, Ki; Liebal, Jessica; Liebig, Wolfgang; Limbach, Christian; Limosani, Antonio; Limper, Maaike; Lin, Simon; Linde, Frank; Lindquist, Brian Edward; Linnemann, James; Lipeles, Elliot; Lipniacka, Anna; Lisovyi, Mykhailo; Liss, Tony; Lissauer, David; Lister, Alison; Litke, Alan; Liu, Dong; Liu, Jianbei; Liu, Kun; Liu, Lulu; Liu, Miaoyuan; Liu, Minghui; Liu, Yanwen; Livan, Michele; Livermore, Sarah; Lleres, Annick; Llorente Merino, Javier; Lloyd, Stephen; Lo Sterzo, Francesco; Lobodzinska, Ewelina; Loch, Peter; Lockman, William; Loddenkoetter, Thomas; Loebinger, Fred; Loevschall-Jensen, Ask Emil; Loginov, Andrey; Loh, Chang Wei; Lohse, Thomas; Lohwasser, Kristin; Lokajicek, Milos; Lombardo, Vincenzo Paolo; Long, Robin Eamonn; Lopes, Lourenco; Lopez Mateos, David; Lorenz, Jeanette; Lorenzo Martinez, Narei; Losada, Marta; Loscutoff, Peter; Losty, Michael; Lou, XinChou; Lounis, Abdenour; Loureiro, Karina; Love, Jeremy; Love, Peter; Lowe, Andrew; Lu, Feng; Lubatti, Henry; Luci, Claudio; Lucotte, Arnaud; Ludwig, Dörthe; Ludwig, Inga; Ludwig, Jens; Luehring, Frederick; Lukas, Wolfgang; Luminari, Lamberto; Lund, Esben; Lundberg, Johan; Lundberg, Olof; Lund-Jensen, Bengt; Lundquist, Johan; Lungwitz, Matthias; Lynn, David; Lysak, Roman; Lytken, Else; Ma, Hong; Ma, Lian Liang; Maccarrone, Giovanni; Macchiolo, Anna; Maček, Boštjan; Machado Miguens, Joana; Macina, Daniela; Mackeprang, Rasmus; Madar, Romain; Madaras, Ronald; Maddocks, Harvey Jonathan; Mader, Wolfgang; Madsen, Alexander; Maeno, Mayuko; Maeno, Tadashi; Magnoni, Luca; Magradze, Erekle; Mahboubi, Kambiz; Mahlstedt, Joern; Mahmoud, Sara; Mahout, Gilles; Maiani, Camilla; Maidantchik, Carmen; Maio, Amélia; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Mal, Prolay; Malaescu, Bogdan; Malecki, Pawel; Malecki, Piotr; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Caitlin; Maltezos, Stavros; Malyshev, Vladimir; Malyukov, Sergei; Mamuzic, Judita; Mandelli, Luciano; Mandić, Igor; Mandrysch, Rocco; Maneira, José; Manfredini, Alessandro; Manhaes de Andrade Filho, Luciano; Manjarres Ramos, Joany Andreina; Mann, Alexander; Manning, Peter; Manousakis-Katsikakis, Arkadios; Mansoulie, Bruno; Mantifel, Rodger; Mapelli, Livio; March, Luis; Marchand, Jean-Francois; Marchese, Fabrizio; Marchiori, Giovanni; Marcisovsky, Michal; Marino, Christopher; Marques, Carlos; Marroquim, Fernando; Marshall, Zach; Marti, Lukas Fritz; Marti-Garcia, Salvador; Martin, Brian; Martin, Brian Thomas; Martin, Jean-Pierre; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martinez, Homero; Martinez, Mario; Martin-Haugh, Stewart; Martyniuk, Alex; Marx, Marilyn; Marzano, Francesco; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Massa, Ignazio; Massol, Nicolas; Mastrandrea, Paolo; Mastroberardino, Anna; Masubuchi, Tatsuya; Matsunaga, Hiroyuki; Matsushita, Takashi; Mättig, Peter; Mättig, Stefan; Mattravers, Carly; Maurer, Julien; Maxfield, Stephen; Maximov, Dmitriy; Mazini, Rachid; Mazur, Michael; Mazzaferro, Luca; Mazzanti, Marcello; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Robert; McCarthy, Tom; McCubbin, Norman; McFarlane, Kenneth; Mcfayden, Josh; Mchedlidze, Gvantsa; Mclaughlan, Tom; McMahon, Steve; McPherson, Robert; Meade, Andrew; Mechnich, Joerg; Mechtel, Markus; Medinnis, Mike; Meehan, Samuel; Meera-Lebbai, Razzak; Meguro, Tatsuma; Mehlhase, Sascha; Mehta, Andrew; Meier, Karlheinz; Meineck, Christian; Meirose, Bernhard; Melachrinos, Constantinos; Mellado Garcia, Bruce Rafael; Meloni, Federico; Mendoza Navas, Luis; Mengarelli, Alberto; Menke, Sven; Meoni, Evelin; Mercurio, Kevin Michael; Meric, Nicolas; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Merritt, Hayes; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Carsten; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Meyer, Joerg; Michal, Sebastien; Middleton, Robin; Migas, Sylwia; Mijović, Liza; Mikenberg, Giora; Mikestikova, Marcela; Mikuž, Marko; Miller, David; Mills, Bill; Mills, Corrinne; Milov, Alexander; Milstead, David; Milstein, Dmitry; Minaenko, Andrey; Miñano Moya, Mercedes; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Ming, Yao; Mir, Lluisa-Maria; Mirabelli, Giovanni; Mitrevski, Jovan; Mitsou, Vasiliki A; Mitsui, Shingo; Miyagawa, Paul; Mjörnmark, Jan-Ulf; Moa, Torbjoern; Moeller, Victoria; Mohapatra, Soumya; Mohr, Wolfgang; Moles-Valls, Regina; Molfetas, Angelos; Mönig, Klaus; Monini, Caterina; Monk, James; Monnier, Emmanuel; Montejo Berlingen, Javier; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Mora Herrera, Clemencia; Moraes, Arthur; Morange, Nicolas; Morel, Julien; Moreno, Deywis; Moreno Llácer, María; Morettini, Paolo; Morgenstern, Marcus; Morii, Masahiro; Moritz, Sebastian; Morley, Anthony Keith; Mornacchi, Giuseppe; Morris, John; Morvaj, Ljiljana; Möser, Nicolas; Moser, Hans-Guenther; Mosidze, Maia; Moss, Josh; Mount, Richard; Mountricha, Eleni; Mouraviev, Sergei; Moyse, Edward; Mudd, Richard; Mueller, Felix; Mueller, James; Mueller, Klemens; Mueller, Thibaut; Mueller, Timo; Muenstermann, Daniel; Munwes, Yonathan; Murillo Quijada, Javier Alberto; Murray, Bill; Mussche, Ido; Musto, Elisa; Myagkov, Alexey; Myska, Miroslav; Nackenhorst, Olaf; Nadal, Jordi; Nagai, Koichi; Nagai, Ryo; Nagai, Yoshikazu; Nagano, Kunihiro; Nagarkar, Advait; Nagasaka, Yasushi; Nagel, Martin; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Namasivayam, Harisankar; Nanava, Gizo; Napier, Austin; Narayan, Rohin; Nash, Michael; Nattermann, Till; Naumann, Thomas; Navarro, Gabriela; Neal, Homer; Nechaeva, Polina; Neep, Thomas James; Negri, Andrea; Negri, Guido; Negrini, Matteo; Nektarijevic, Snezana; Nelson, Andrew; Nelson, Timothy Knight; Nemecek, Stanislav; Nemethy, Peter; Nepomuceno, Andre Asevedo; Nessi, Marzio; Neubauer, Mark; Neumann, Manuel; Neusiedl, Andrea; Neves, Ricardo; Nevski, Pavel; Newcomer, Mitchel; Newman, Paul; Nguyen, Duong Hai; Nguyen Thi Hong, Van; Nickerson, Richard; Nicolaidou, Rosy; Nicquevert, Bertrand; Niedercorn, Francois; Nielsen, Jason; Nikiforou, Nikiforos; Nikiforov, Andriy; Nikolaenko, Vladimir; Nikolic-Audit, Irena; Nikolics, Katalin; Nikolopoulos, Konstantinos; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nisius, Richard; Nobe, Takuya; Nodulman, Lawrence; Nomachi, Masaharu; Nomidis, Ioannis; Norberg, Scarlet; Nordberg, Markus; Novakova, Jana; Nozaki, Mitsuaki; Nozka, Libor; Nuncio-Quiroz, Adriana-Elizabeth; Nunes Hanninger, Guilherme; Nunnemann, Thomas; Nurse, Emily; O'Brien, Brendan Joseph; O'Neil, Dugan; O'Shea, Val; Oakes, Louise Beth; Oakham, Gerald; Oberlack, Horst; Ocariz, Jose; Ochi, Atsuhiko; Ochoa, Ines; Oda, Susumu; Odaka, Shigeru; Odier, Jerome; Ogren, Harold; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohshima, Takayoshi; Okamura, Wataru; Okawa, Hideki; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Olchevski, Alexander; Olivares Pino, Sebastian Andres; Oliveira, Miguel Alfonso; Oliveira Damazio, Denis; Oliver Garcia, Elena; Olivito, Dominick; Olszewski, Andrzej; Olszowska, Jolanta; Onofre, António; Onyisi, Peter; Oram, Christopher; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orlando, Nicola; 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2013-09-13

This paper presents the application of a variety of techniques to study jet substructure. The performance of various modified jet algorithms, or jet grooming techniques, for several jet types and event topologies is investigated for jets with transverse momentum larger than 300 GeV. Properties of jets subjected to the mass-drop filtering, trimming, and pruning algorithms are found to have reduced sensitivity to multiple proton-proton interactions, are more stable at high luminosity and improve the physics potential of searches for heavy boosted objects. Studies of the expected discrimination power of jet mass and jet substructure observables in searches for new physics are also presented. Event samples enriched in boosted W and Z bosons and top-quark pairs are used to study both the individual jet invariant mass scales and the efficacy of algorithms to tag boosted hadronic objects. The analyses presented use the full 2011 ATLAS dataset, corresponding to an integrated luminosity of 4.7 $\\pm$ 0.1 /fb from proto...

Probing the Influence of Linker Length and Flexibility in the Design and Synthesis of New Trehalase Inhibitors

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Giampiero D’Adamio

2018-02-01

Full Text Available This work aims to synthesize new trehalase inhibitors selective towards the insect trehalase versus the porcine trehalase, in view of their application as potentially non-toxic insecticides and fungicides. The synthesis of a new pseudodisaccharide mimetic 8, by means of a stereoselective α-glucosylation of the key pyrrolizidine intermediate 13, was accomplished. The activity of compound 8 as trehalase inhibitor towards C. riparius trehalase was evaluated and the results showed that 8 was active in the μM range and showed a good selectivity towards the insect trehalase. To reduce the overall number of synthetic steps, simpler and more flexible disaccharide mimetics 9–11 bearing a pyrrolidine nucleus instead of the pyrrolizidine core were synthesized. The biological data showed the key role of the linker chain’s length in inducing inhibitory properties, since only compounds 9 (α,β-mixture, bearing a two-carbon atom linker chain, maintained activity as trehalase inhibitors. A proper change in the glucosyl donor-protecting groups allowed the stereoselective synthesis of the β-glucoside 9β, which was active in the low micromolar range (IC50 = 0.78 μM and 12-fold more potent (and more selective than 9α towards the insect trehalase.

Parsing the roles of neck-linker docking and tethered head diffusion in the stepping dynamics of kinesin.

Science.gov (United States)

Zhang, Zhechun; Goldtzvik, Yonathan; Thirumalai, D

2017-11-14

Kinesin walks processively on microtubules (MTs) in an asymmetric hand-over-hand manner consuming one ATP molecule per 16-nm step. The individual contributions due to docking of the approximately 13-residue neck linker to the leading head (deemed to be the power stroke) and diffusion of the trailing head (TH) that contributes in propelling the motor by 16 nm have not been quantified. We use molecular simulations by creating a coarse-grained model of the MT-kinesin complex, which reproduces the measured stall force as well as the force required to dislodge the motor head from the MT, to show that nearly three-quarters of the step occurs by bidirectional stochastic motion of the TH. However, docking of the neck linker to the leading head constrains the extent of diffusion and minimizes the probability that kinesin takes side steps, implying that both the events are necessary in the motility of kinesin and for the maintenance of processivity. Surprisingly, we find that during a single step, the TH stochastically hops multiple times between the geometrically accessible neighboring sites on the MT before forming a stable interaction with the target binding site with correct orientation between the motor head and the [Formula: see text] tubulin dimer.

Free Vibration Analysis of a Spinning Flexible DISK-SPINDLE System Supported by Ball Bearing and Flexible Shaft Using the Finite Element Method and Substructure Synthesis

Science.gov (United States)

JANG, G. H.; LEE, S. H.; JUNG, M. S.

2002-03-01

Free vibration of a spinning flexible disk-spindle system supported by ball bearing and flexible shaft is analyzed by using Hamilton's principle, FEM and substructure synthesis. The spinning disk is described by using the Kirchhoff plate theory and von Karman non-linear strain. The rotating spindle and stationary shaft are modelled by Rayleigh beam and Euler beam respectively. Using Hamilton's principle and including the rigid body translation and tilting motion, partial differential equations of motion of the spinning flexible disk and spindle are derived consistently to satisfy the geometric compatibility in the internal boundary between substructures. FEM is used to discretize the derived governing equations, and substructure synthesis is introduced to assemble each component of the disk-spindle-bearing-shaft system. The developed method is applied to the spindle system of a computer hard disk drive with three disks, and modal testing is performed to verify the simulation results. The simulation result agrees very well with the experimental one. This research investigates critical design parameters in an HDD spindle system, i.e., the non-linearity of a spinning disk and the flexibility and boundary condition of a stationary shaft, to predict the free vibration characteristics accurately. The proposed method may be effectively applied to predict the vibration characteristics of a spinning flexible disk-spindle system supported by ball bearing and flexible shaft in the various forms of computer storage device, i.e., FDD, CD, HDD and DVD.

Substructuring of multibody systems for numerical transfer path analysis in internal combustion engines

Science.gov (United States)

Acri, Antonio; Offner, Guenter; Nijman, Eugene; Rejlek, Jan

2016-10-01

Noise legislations and the increasing customer demands determine the Noise Vibration and Harshness (NVH) development of modern commercial vehicles. In order to meet the stringent legislative requirements for the vehicle noise emission, exact knowledge of all vehicle noise sources and their acoustic behavior is required. Transfer path analysis (TPA) is a fairly well established technique for estimating and ranking individual low-frequency noise or vibration contributions via the different transmission paths. Transmission paths from different sources to target points of interest and their contributions can be analyzed by applying TPA. This technique is applied on test measurements, which can only be available on prototypes, at the end of the designing process. In order to overcome the limits of TPA, a numerical transfer path analysis methodology based on the substructuring of a multibody system is proposed in this paper. Being based on numerical simulation, this methodology can be performed starting from the first steps of the designing process. The main target of the proposed methodology is to get information of noise sources contributions of a dynamic system considering the possibility to have multiple forces contemporary acting on the system. The contributions of these forces are investigated with particular focus on distribute or moving forces. In this paper, the mathematical basics of the proposed methodology and its advantages in comparison with TPA will be discussed. Then, a dynamic system is investigated with a combination of two methods. Being based on the dynamic substructuring (DS) of the investigated model, the methodology proposed requires the evaluation of the contact forces at interfaces, which are computed with a flexible multi-body dynamic (FMBD) simulation. Then, the structure-borne noise paths are computed with the wave based method (WBM). As an example application a 4-cylinder engine is investigated and the proposed methodology is applied on the

THE NEXT GENERATION VIRGO CLUSTER SURVEY. XIX. TOMOGRAPHY OF MILKY WAY SUBSTRUCTURES IN THE NGVS FOOTPRINT

Energy Technology Data Exchange (ETDEWEB)

Lokhorst, Deborah; Starkenburg, Else; Navarro, Julio F. [Department of Physics and Astronomy, University of Victoria, Victoria, BC V8P 1A1, Canada (Canada); McConnachie, Alan W.; Ferrarese, Laura; Côté, Patrick; Gwyn, Stephen D. J. [National Research Council, Herzberg Astronomy and Astrophysics, 5071 West Saanich Road, Victoria, BC V9E 2E7 (Canada); Liu, Chengze [Center for Astronomy and Astrophysics, Department of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai 200240 (China); Peng, Eric W. [Department of Astronomy, Peking University, Beijing 100871 (China); Cuillandre, Jean-Charles [CEA/IRFU/SAP, Laboratoire AIM Paris-Saclay, CNRS/INSU, Université Paris Diderot, Observatoire de Paris, PSL Research University, F-91191 Gif-sur-Yvette Cedex (France); Guhathakurta, Puragra, E-mail: dml@uvic.ca [Department of Astronomy and Astrophysics, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95064 (United States)

2016-03-10

The Next Generation Virgo Cluster Survey (NGVS) is a deep u*giz survey targeting the Virgo Cluster of galaxies at 16.5 Mpc. This survey provides high-quality photometry over an ∼100 deg{sup 2} region straddling the constellations of Virgo and Coma Berenices. This sightline through the Milky Way is noteworthy in that it intersects two of the most prominent substructures in the Galactic halo: the Virgo overdensity (VOD) and Sagittarius stellar stream (close to its bifurcation point). In this paper, we use deep u*gi imaging from the NGVS to perform tomography of the VOD and Sagittarius stream using main-sequence turnoff (MSTO) stars as a halo tracer population. The VOD, whose centroid is known to lie at somewhat lower declinations (α ∼ 190°, δ ∼ −5°) than is covered by the NGVS, is nevertheless clearly detected in the NGVS footprint at distances between ∼8 and 25 kpc. By contrast, the Sagittarius stream is found to slice directly across the NGVS field at distances between 25 and 40 kpc, with a density maximum at ≃35 kpc. No evidence is found for new substructures beyond the Sagittarius stream, at least out to a distance of ∼90 kpc—the largest distance to which we can reliably trace the halo using MSTO stars. We find clear evidence for a distance gradient in the Sagittarius stream across the ∼30° of sky covered by the NGVS and its flanking fields. We compare our distance measurements along the stream with those predicted by leading stream models.

THE NEXT GENERATION VIRGO CLUSTER SURVEY. XIX. TOMOGRAPHY OF MILKY WAY SUBSTRUCTURES IN THE NGVS FOOTPRINT

International Nuclear Information System (INIS)

Lokhorst, Deborah; Starkenburg, Else; Navarro, Julio F.; McConnachie, Alan W.; Ferrarese, Laura; Côté, Patrick; Gwyn, Stephen D. J.; Liu, Chengze; Peng, Eric W.; Cuillandre, Jean-Charles; Guhathakurta, Puragra

2016-01-01

The Next Generation Virgo Cluster Survey (NGVS) is a deep u*giz survey targeting the Virgo Cluster of galaxies at 16.5 Mpc. This survey provides high-quality photometry over an ∼100 deg 2 region straddling the constellations of Virgo and Coma Berenices. This sightline through the Milky Way is noteworthy in that it intersects two of the most prominent substructures in the Galactic halo: the Virgo overdensity (VOD) and Sagittarius stellar stream (close to its bifurcation point). In this paper, we use deep u*gi imaging from the NGVS to perform tomography of the VOD and Sagittarius stream using main-sequence turnoff (MSTO) stars as a halo tracer population. The VOD, whose centroid is known to lie at somewhat lower declinations (α ∼ 190°, δ ∼ −5°) than is covered by the NGVS, is nevertheless clearly detected in the NGVS footprint at distances between ∼8 and 25 kpc. By contrast, the Sagittarius stream is found to slice directly across the NGVS field at distances between 25 and 40 kpc, with a density maximum at ≃35 kpc. No evidence is found for new substructures beyond the Sagittarius stream, at least out to a distance of ∼90 kpc—the largest distance to which we can reliably trace the halo using MSTO stars. We find clear evidence for a distance gradient in the Sagittarius stream across the ∼30° of sky covered by the NGVS and its flanking fields. We compare our distance measurements along the stream with those predicted by leading stream models

Guided Iterative Substructure Search (GI-SSS) - A New Trick for an Old Dog.

Science.gov (United States)

Weskamp, Nils

2016-07-01

Substructure search (SSS) is a fundamental technique supported by various chemical information systems. Many users apply it in an iterative manner: they modify their queries to shape the composition of the retrieved hit sets according to their needs. We propose and evaluate two heuristic extensions of SSS aimed at simplifying these iterative query modifications by collecting additional information during query processing and visualizing this information in an intuitive way. This gives the user a convenient feedback on how certain changes to the query would affect the retrieved hit set and reduces the number of trial-and-error cycles needed to generate an optimal search result. The proposed heuristics are simple, yet surprisingly effective and can be easily added to existing SSS implementations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A model for Quick Load Analysis for monopile-type offshore wind turbine substructures

DEFF Research Database (Denmark)

Schløer, Signe; Castillo, Laura Garcia; Fejerskov, Morten

2016-01-01

A model for Quick Load Analysis, QuLA, of an offshore wind turbine substructure is presented. The aerodynamic rotor loads and damping are precomputed for a load-based configuration. The dynamic structural response is represented by the first global fore-aft mode only and is computed...... in the frequency domain using the equation of motion. The model is compared against the state of the art aeroelastic code, Flex5, and both life time fatigue and extreme loads are considered in the comparison. In general there is good similarity between the two models. Some derivation for the sectional forces...... are explained in terms of the model simplifications. The difference in the sectional moments are found to be within 14% for the fatigue load case and 10% for the extreme load condition....

Traceless Azido Linker for the Solid-Phase Synthesis of NH-1,2,3-Triazoles via Cu-Catalyzed Azide-Alkyne Cycloaddition Reactions

DEFF Research Database (Denmark)

Cohrt, Anders Emil; Jensen, Jakob Feldthusen; Nielsen, Thomas Eiland

2010-01-01

A broadly useful acid-labile traceless azido linker for the solid-phase synthesis of NH-1,2,3-triazoles is presented. A variety of alkynes were efficiently immobilized on a range of polymeric supports by Cu(I)-mediated azide-alkyne cycloadditions. Supported triazoles showed excellent compatibility...

Transpiration cooling assisted ablative thermal protection of aerospace substructures

International Nuclear Information System (INIS)

Khan, M.B.; Iqbal, N.; Haider, Z.

2009-01-01

Ablatives are heat-shielding materials used to protect aerospace substructures. These materials are sacrificial in nature and provide protection primarily through the large endothermic transformation during exposure to hyper thermal environment such as encountered in re-entry modules. The performance of certain ablatives was reported in terms of their TGA/DTA in Advanced Materials-97 (pp 57-65). The focus of this earlier research resided in the consolidation of interface between the refractory inclusion and the host polymeric matrix to improve thermal resistance. In the present work we explore the scope of transpiration cooling in ablative performance through flash evaporation of liquid incorporated in the host EPDM (Ethylene Propylene Diene Monomer) matrix. The compression-molded specimens were exposed separately to plasma flame (15000 C) and oxyacetylene torch (3000 C) and the back face transient temperature is recorded in situ employing a thermocouple/data logger system. Both head on impingement (HOI) and parallel flow (PF) through a central cavity in the ablator were used. It is observed that transpiration cooling is effective and yields (a) rapid thermal equilibrium in the specimen, (b) lower back face temperature and (c) lower ablation rate, compared to conventional ablatives. SEM/EDS analysis is presented to amplify the point. (author)

Synthesis and catalytic evaluation in the Heck reaction of deposited palladium catalysts immobilized via amide linkers and their molecular analogues

Czech Academy of Sciences Publication Activity Database

Semler, M.; Čejka, Jiří; Štěpnička, P.

2014-01-01

Roč. 227, MAY 2014 (2014), s. 207-214 ISSN 0920-5861 R&D Projects: GA ČR GA104/09/0561; GA ČR(CZ) GA13-08944S Institutional support: RVO:61388955 Keywords : deposited catalysts * palladium * amide linkers Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.893, year: 2014

Plastic deformation of uranium dioxide: observation of the sub-structures of dislocations

International Nuclear Information System (INIS)

Alamo, A.; Lefebvre, J.M.; Soullard, J.

1978-01-01

Single crystals of uranium dioxide were deformed in compression at imposed strain rates in the temperature range of 700 0 C to 1400 0 C. The crystals were oriented to promote slip over one or two slip systems of the family [100] and also on the [110] system. Thin films of the deformed specimens were examined by transmission electron microscopy. When [100] single glide system operates, the dislocation substructure consist of numerous dipoles, their edge components lying along directions. For the [100] double glide system the grain boundaries and dislocation hexagonal network are observed, the complexity of which increases with the nominal strain. Dislocation arrangments consisting of extensive cellular networks of tangling dislocations and hexagonal netting were detected for [110] system. The auxillary role of [111] planes on the dislocation cross slip from [100] and [110] system was demonstrated. Weak beam images suggest that dissociation of dislocations can occur. (Auth.)

The Substructure of a Flux Transfer Event Observed by the MMS Spacecraft

Science.gov (United States)

Hwang, K.-J.; Sibeck, D. G.; Giles, B. L.; Pollock, C. J.; Gershman, D.; Avanov, L.; Paterson, W. R.; Dorelli, J. C.; Ergun, R. E.; Russel, C. T.;

Orientation dependence of shock-induced twinning and substructures in a copper bicrystal

International Nuclear Information System (INIS)

Cao Fang; Beyerlein, Irene J.; Addessio, Francis L.; Sencer, Bulent H.; Trujillo, Carl P.; Cerreta, Ellen K.; Gray, George T. III

2010-01-01

Shock recovery experiments have been conducted to assess the role of shock stress and orientation dependence on substructure evolution and deformation twinning of a [1 0 0]/[011-bar] copper bicrystal. Transmission electron microscopy of the post-shock specimens revealed that well-defined dislocation cell structures developed in both grains and the average cell size decreased with increasing shock pressure from 5 to 10 GPa. Twinning occurred in the [1 0 0] grain, but not the [011-bar] grain, at the 10 GPa shock pressure. The stress and orientation dependence of incipient twinning can be predicted by the stress and orientation conditions required to dissociate slip dislocations into glissile twinning dislocations. The dynamic widths between the two partials are calculated considering the three-dimensional deviatoric stress state induced by the shock as calculated using plane-strain plate impact simulations and the relativistic and drag effects on dislocations moving at high speeds.

Multivalent cyclic RGD ligands: influence of linker lengths on receptor binding

Energy Technology Data Exchange (ETDEWEB)

Kubas, Holger; Schaefer, Martin; Bauder-Wuest, Ulrike; Eder, Matthias; Oltmanns, Doerte [Department of Radiopharmaceutical Chemistry, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Haberkorn, Uwe; Mier, Walter [Department of Nuclear Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg (Germany); Eisenhut, Michael, E-mail: m.eisenhut@dkfz.d [Department of Radiopharmaceutical Chemistry, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)

2010-11-15

Peptides involving the RGD motive (arginine-glycine-aspartic acid) recognize members of the integrin receptor family. Since the receptors are located mainly on the surface of endothelial cells, structural modifications including multimers of c(RGDfE) were recently found to improve the binding avidity for {alpha}{sub v{beta}3} integrin significantly. The multivalent RGD peptides exhibited rather loose linkages partly including oligo(ethylene glycol) spacers (EG{sub n}) with different chain lengths. Therefore, the dependence of multivalent RGD systems with and without EG{sub n} linkers were investigated on their binding properties to cultured {alpha}{sub v{beta}3} integrin-expressing U87MG cells. Methods: We synthesized a series of di-, tri- and tetravalent rigid scaffolds (terephthalic acid, trimesic acid and adamantane-1,3,5,7-tetracarboxylic acid) conjugated to c(RGDyK) ligands, which were linked contiguously or separated by the oligo(ethylene glycol) spacers. The inhibition constants of these c(RGDyK) derivatives were determined by competition assays with {sup 125}I-labeled echistatin. Results: While c(RGDyK) function is a relative weak competitor against [{sup 125}I]echistatin (K{sub i}, 329{+-}18 nM) for {alpha}{sub v{beta}3} integrin-expressing U87MG cells, RGD dimers improved the competition potency considerably (K{sub i}, 64{+-}23 nM). This effect was even more pronounced with the RGD trimers (K{sub i}, 40{+-}7 nM) and tetramers (K{sub i}, 26{+-}9 nM). The introduction of EG{sub n} spacers and the increase of linker lengths proved to be detrimental since more competitors were needed to compete with [{sup 125}I]echistatin. The EG{sub 6} group, for example, reduced the inhibition constants by 29% (dimer), 57% (trimer) and 97% (tetramer). Conclusion: The binding experiments performed with the three forms of multivalent RGD ligands indicate the weakening of competitive potency against [{sup 125}I]echistatin with the introduction of EG{sub n} spacers. This effect

Structural Polymorphism of the Actin-Espin System: A Prototypical System of Filaments and Linkers in Stereocilia

International Nuclear Information System (INIS)

Purdy, Kirstin R.; Wong, Gerard C. L.; Bartles, James R.

2007-01-01

We examine the interaction between cytoskeletal F-actin and espin 3A, a prototypical actin bundling protein found in sensory cell microvilli, including ear cell stereocilia. Espin induces twist distortions in F-actin as well as facilitates bundle formation. Mutations in one of the two F-actin binding sites of espin, which have been implicated in deafness, can tune espin-actin interactions and radically transform the system's phase behavior. These results are compared to recent theoretical work on the general phase behavior linker-rod systems

The role of H1 linker histone subtypes in preserving the fidelity of elaboration of mesendodermal and neuroectodermal lineages during embryonic development.

Directory of Open Access Journals (Sweden)

Giang D Nguyen

Full Text Available H1 linker histone proteins are essential for the structural and functional integrity of chromatin and for the fidelity of additional epigenetic modifications. Deletion of H1c, H1d and H1e in mice leads to embryonic lethality by mid-gestation with a broad spectrum of developmental alterations. To elucidate the cellular and molecular mechanisms underlying H1 linker histone developmental functions, we analyzed embryonic stem cells (ESCs depleted of H1c, H1d and H1e subtypes (H1-KO ESCs by utilizing established ESC differentiation paradigms. Our study revealed that although H1-KO ESCs continued to express core pluripotency genes and the embryonic stem cell markers, alkaline phosphatase and SSEA1, they exhibited enhanced cell death during embryoid body formation and during specification of mesendoderm and neuroectoderm. In addition, we demonstrated deregulation in the developmental programs of cardiomyocyte, hepatic and pancreatic lineage elaboration. Moreover, ectopic neurogenesis and cardiomyogenesis occurred during endoderm-derived pancreatic but not hepatic differentiation. Furthermore, neural differentiation paradigms revealed selective impairments in the specification and maturation of glutamatergic and dopaminergic neurons with accelerated maturation of glial lineages. These impairments were associated with deregulation in the expression profiles of pro-neural genes in dorsal and ventral forebrain-derived neural stem cell species. Taken together, these experimental observations suggest that H1 linker histone proteins are critical for the specification, maturation and fidelity of organ-specific cellular lineages derived from the three cardinal germ layers.

Epigenetics and autism spectrum disorder: A report of an autism case with mutation in H1 linker histone HIST1H1e and literature review.

Science.gov (United States)

Duffney, Lara J; Valdez, Purnima; Tremblay, Martine W; Cao, Xinyu; Montgomery, Sarah; McConkie-Rosell, Allyn; Jiang, Yong-Hui

2018-04-27

Genetic mutations in genes encoding proteins involved in epigenetic machinery have been reported in individuals with autism spectrum disorder (ASD), intellectual disability, congenital heart disease, and other disorders. H1 histone linker protein, the basic component in nucleosome packaging and chromatin organization, has not been implicated in human disease until recently. We report a de novo deleterious mutation of histone cluster 1 H1 family member e (HIST1H1E; c.435dupC; p.Thr146Hisfs*50), encoding H1 histone linker protein H1.4, in a 10-year-old boy with autism and intellectual disability diagnosed through clinical whole exome sequencing. The c.435dupC at the 3' end of the mRNA leads to a frameshift and truncation of the positive charge in the carboxy-terminus of the protein. An expression study demonstrates the mutation leads to reduced protein expression, supporting haploinsufficiency of HIST1H1E protein and loss of function as an underlying mechanism of dysfunction in the brain. Taken together with other recent cases with mutations of HIST1H1E in intellectual disability, the evidence supporting the link to causality in disease is strong. Our finding implicates the deficiency of H1 linker histone protein in autism. The systematic review of candidate genes implicated in ASD revealed that 42 of 215 (19.5%) genes are directly involved in epigenetic regulations and the majority of these genes belong to histone writers, readers, and erasers. While the mechanism of how haploinsufficiency of HIST1H1E causes autism is entirely unknown, our report underscores the importance of further study of the function of this protein and other histone linker proteins in brain development. © 2018 Wiley Periodicals, Inc.

Exploring halo substructure with giant stars. XIV. The nature of the Triangulum-Andromeda stellar features

Energy Technology Data Exchange (ETDEWEB)

Sheffield, Allyson A.; Johnston, Kathryn V. [Department of Astronomy, Columbia University, Mail Code 5246, New York, NY 10027 (United States); Majewski, Steven R.; Damke, Guillermo; Richardson, Whitney; Beaton, Rachael [Department of Astronomy, University of Virginia, P.O. Box 400325, Charlottesville, VA 22904 (United States); Rocha-Pinto, Helio J., E-mail: asheffield@astro.columbia.edu, E-mail: kvj@astro.columbia.edu, E-mail: srm4n@virginia.edu, E-mail: gjd3r@virginia.edu, E-mail: wwr2u@virginia.edu, E-mail: rlb9n@virginia.edu, E-mail: helio@astro.ufrj.br [Observatório do Valongo, Universidade Federal do Rio de Janeiro, Rio de Janeiro (Brazil)

2014-09-20

As large-scale stellar surveys have become available over the past decade, the ability to detect and characterize substructures in the Galaxy has increased dramatically. These surveys have revealed the Triangulum-Andromeda (TriAnd) region to be rich with substructures in the distance range 20-30 kpc, and the relation of these features to each other, if any, remains unclear. An exploration using Two Micron All Sky Survey (2MASS) photometry reveals not only the faint sequence in M giants detected by Rocha-Pinto et al. spanning the range 100° < l < 160° and –50° < b < –15°, but, in addition, a second, brighter and more densely populated sequence. These sequences are likely associated with the distinct main sequences (MSs) discovered (and labeled TriAnd1 and TriAnd2) by Martin et al. in an optical survey in the direction of M31, where TriAnd2 is the optical counterpart of the fainter red giant branch (RGB)/asymptotic giant branch sequence of Rocha-Pinto et al. Here, the age, distance, and metallicity ranges for TriAnd1 and TriAnd2 are estimated by simultaneously fitting isochrones to the 2MASS RGB tracks and the optical MS/MS turn-off features. The two populations are clearly distinct in age and distance: the brighter sequence (TriAnd1) is younger (6-10 Gyr) and closer (distance of ∼15-21 kpc), whereas the fainter sequence (TriAnd2) is older (10-12 Gyr) and at an estimated distance of ∼24-32 kpc. A comparison with simulations demonstrates that the differences and similarities between TriAnd1 and TriAnd2 can simultaneously be explained if they represent debris originating from the disruption of the same dwarf galaxy, but torn off during two distinct pericentric passages.

Global Profiling and Novel Structure Discovery Using Multiple Neutral Loss/Precursor Ion Scanning Combined with Substructure Recognition and Statistical Analysis (MNPSS): Characterization of Terpene-Conjugated Curcuminoids in Curcuma longa as a Case Study.

Science.gov (United States)

Qiao, Xue; Lin, Xiong-hao; Ji, Shuai; Zhang, Zheng-xiang; Bo, Tao; Guo, De-an; Ye, Min

2016-01-05

To fully understand the chemical diversity of an herbal medicine is challenging. In this work, we describe a new approach to globally profile and discover novel compounds from an herbal extract using multiple neutral loss/precursor ion scanning combined with substructure recognition and statistical analysis. Turmeric (the rhizomes of Curcuma longa L.) was used as an example. This approach consists of three steps: (i) multiple neutral loss/precursor ion scanning to obtain substructure information; (ii) targeted identification of new compounds by extracted ion current and substructure recognition; and (iii) untargeted identification using total ion current and multivariate statistical analysis to discover novel structures. Using this approach, 846 terpecurcumins (terpene-conjugated curcuminoids) were discovered from turmeric, including a number of potentially novel compounds. Furthermore, two unprecedented compounds (terpecurcumins X and Y) were purified, and their structures were identified by NMR spectroscopy. This study extended the application of mass spectrometry to global profiling of natural products in herbal medicines and could help chemists to rapidly discover novel compounds from a complex matrix.

Preparation, structural analysis and bioactivity of ribonuclease A-albumin conjugate: tetra-conjugation or PEG as the linker.

Science.gov (United States)

Li, Chunju; Lin, Qixun; Wang, Jun; Shen, Lijuan; Ma, Guanghui; Su, Zhiguo; Hu, Tao

2012-12-31

Ribonuclease A (RNase A) is a therapeutic enzyme with cytotoxic action against tumor cells. Its clinical application is limited by the short half-life and insufficient stability. Conjugation of albumin can overcome the limitation, whereas dramatically decrease the enzymatic activity of RNase A. Here, three strategies were proposed to prepare the RNase A-bovine serum albumin (BSA) conjugates. R-SMCC-B (a conjugate of four RNase A attached with one BSA) and R-PEG-B (a mono-conjugate) were prepared using Sulfo-SMCC (a short bifunctional linker) and mal-PEG-NHS (a bifunctional PEG), respectively. Mal-PEG-NHS and hexadecylamine (HDA) were used to prepare the mono-conjugate, R-HDA-B, where HDA was adopted to bind BSA. The PEG linker can elongate the proximity between RNase A and BSA. In contrast, four RNase A were closely located on BSA in R-SMCC-B. R-SMCC-B showed the lowest K(m) and the highest relative enzymatic activity and k(cat)/K(m) in the three conjugates. Presumably, the tetravalent interaction of RNase A in R-SMCC-B can increase the binding affinity to its substrate. In addition, the slow release of BSA from R-HDA-B may increase the enzymatic activity of R-HDA-B. Our study is expected to provide strategies to develop protein-albumin conjugate with high therapeutic potential. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of the Amino Acid Linkers on the Melanoma-Targeting and Pharmacokinetic Properties of Indium-111-labeled Lactam Bridge-Cyclized α-MSH Peptides

Science.gov (United States)

Guo, Haixun; Yang, Jianquan; Gallazzi, Fabio; Miao, Yubin

2011-01-01

The purpose of this study was to examine the profound effects of the amino acid linkers on the melanoma targeting and pharmacokinetic properties of novel 111In-labeled lactam bridge-cyclized DOTA-[X]-CycMSHhex {1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid-[X]-c[Asp-His-dPhe-Arg-Trp-Lys]-CONH2, X=GlyGlyNle, GlyGluNle or NleGlyGlu} peptides. Methods Three novel DOTA-GGNle-CycMSHhex, DOTA-GENle-CycMSHhex and DOTA-NleGE-CycMSHhex peptides were designed and synthesized. The melanocortin-1 (MC1) receptor binding affinities of the peptides were determined in B16/F1 melanoma cells. The melanoma targeting and pharmacokinetic properties of 111In-DOTA-GGNle-CycMSHhex and 111In-DOTA-GENle-CycMSHhex were determined in B16/F1 melanoma-bearing C57 mice. Results DOTA-GGNle-CycMSHhex and DOTA-GENle-CycMSHhex displayed 2.1 and 11.5 nM MC1 receptor binding affinities, whereas DOTA-NleGE-CycMSHhex showed 873.4 nM MC1 receptor binding affinity. The introduction of the -GlyGly- linker maintained high melanoma uptake while decreased the renal and liver uptakes of 111In-DOTA-GlyGlyNle-CycMSHhex. The tumor uptake values of 111In-DOTA-GGNle-CycMSHhex were 19.05 ± 5.04 and 18.6 ± 3.56 % injected dose/gram (%ID/g) at 2 and 4 h post-injection. 111In-DOTA-GGNle-CycMSHhex exhibited 28, 32 and 42% less renal uptake values than 111In-DOTA-Nle-CycMSHhex we reported previously, and 61, 65 and 68% less liver uptake values than 111In-DOTA-Nle-CycMSHhex at 2, 4 and 24 h post-injection, respectively. Conclusion The amino acid linkers exhibited the profound effects on the melanoma targeting and pharmacokinetic properties of the 111In-labeled lactam bridge-cyclized α-MSH peptides. Introduction of the -GlyGly- linker maintained high melanoma uptake while reducing the renal and liver uptakes of 111In-DOTA-GlyGlyNle-CycMSHhex, highlighting its potential as an effective imaging probe for melanoma detection, as well as a therapeutic peptide for melanoma treatment when labeled with a therapeutic

Optimizing the relaxivity of GdIII complexes appended to InP/ZnS quantum dots by linker tuning.

Science.gov (United States)

Stasiuk, Graeme J; Tamang, Sudarsan; Imbert, Daniel; Gateau, Christelle; Reiss, Peter; Fries, Pascal; Mazzanti, Marinella

2013-06-21

Three bimodal MRI/optical nanosized contrast agents with high per-nanoparticle relaxivity (up to 2523 mM(-1) s(-1) at 35 MHz and 932 mM(-1) s(-1) at 200 MHz) have been prepared connecting up to 115 tris-aqua Gd(III) complexes to fluorescent non-toxic InP/ZnS quantum dots. The structure of the linker has an important effect on the relaxivity of the final multimeric contrast agent.

Direct observations of dislocation substructures formed by nano-indentation of the α-phase in an α/β titanium alloy

International Nuclear Information System (INIS)

Viswanathan, G.B.; Lee, Eunha; Maher, Dennis M.; Banerjee, Srikumar; Fraser, Hamish L.

2005-01-01

Nano-indentation has been used to assess the hardness of equiaxed grains of α-Ti as a function of orientation. Surface normals of these grains in metallographic sections were assessed using orientation imaging microscopy. Thin membranes of material from below a series of nano-indentations were excised by use of a dual-beam focused ion beam instrument. In this way, the dislocation substructures beneath individual indentations were characterized using transmission electron microscopy, permitting an identification of both statistically stored and geometrically necessary dislocations

Aspects of dislocation substructures associated with the deformation stages of stainless steel AISI 304 at high temperatures

International Nuclear Information System (INIS)

Oliveira, J.L.L.; Reis Filho, J.A.B.S.; Almeida, L.H. de; Monteiro, S.N.

1978-07-01

The development of dislocation substrutures in type 304 austenitic stainless steel at high temperatures has been associated with the deformation stages through log dσ/d epsilon x log epsilon plots, which show the transition point independently. The mechanisms responsible for the Dynamic Strain Aging particulary the Portevin-LeChatelier effect were related to the appearence of the stages. The results indicate that the deformation stages can be divided into two distinct regions. Each one of these region show particular characteristics with respect to the stress level, transition point, developed substructure and type of crystalline defects interaction with dislocations. (Author) [pt

Ancestry inference using principal component analysis and spatial analysis: a distance-based analysis to account for population substructure.

Science.gov (United States)

Byun, Jinyoung; Han, Younghun; Gorlov, Ivan P; Busam, Jonathan A; Seldin, Michael F; Amos, Christopher I

2017-10-16

Accurate inference of genetic ancestry is of fundamental interest to many biomedical, forensic, and anthropological research areas. Genetic ancestry memberships may relate to genetic disease risks. In a genome association study, failing to account for differences in genetic ancestry between cases and controls may also lead to false-positive results. Although a number of strategies for inferring and taking into account the confounding effects of genetic ancestry are available, applying them to large studies (tens thousands samples) is challenging. The goal of this study is to develop an approach for inferring genetic ancestry of samples with unknown ancestry among closely related populations and to provide accurate estimates of ancestry for application to large-scale studies. In this study we developed a novel distance-based approach, Ancestry Inference using Principal component analysis and Spatial analysis (AIPS) that incorporates an Inverse Distance Weighted (IDW) interpolation method from spatial analysis to assign individuals to population memberships. We demonstrate the benefits of AIPS in analyzing population substructure, specifically related to the four most commonly used tools EIGENSTRAT, STRUCTURE, fastSTRUCTURE, and ADMIXTURE using genotype data from various intra-European panels and European-Americans. While the aforementioned commonly used tools performed poorly in inferring ancestry from a large number of subpopulations, AIPS accurately distinguished variations between and within subpopulations. Our results show that AIPS can be applied to large-scale data sets to discriminate the modest variability among intra-continental populations as well as for characterizing inter-continental variation. The method we developed will protect against spurious associations when mapping the genetic basis of a disease. Our approach is more accurate and computationally efficient method for inferring genetic ancestry in the large-scale genetic studies.

SHARP - II. Mass structure in strong lenses is not necessarily dark matter substructure: a flux ratio anomaly from an edge-on disc in B1555+375

NARCIS (Netherlands)

Hsueh, J. -W; Fassnacht, C. D.; Vegetti, S.; McKean, J. P.; Spingola, C.; Auger, M. W.; Koopmans, L. V. E.; Lagattuta, D. J.

2016-01-01

Gravitational lens flux-ratio anomalies provide a powerful technique for measuring dark matter substructure in distant galaxies. However, before using these flux-ratio anomalies to test galaxy formation models, it is imperative to ascertain that the given anomalies are indeed due to the presence of

The First Extracellular Linker Is Important for Several Aspects of the Gating Mechanism of Human TRPA1 Channel

Czech Academy of Sciences Publication Activity Database

Maršáková, Lenka; Barvík, I.; Zíma, V.; Zímová, Lucie; Vlachová, Viktorie

2017-01-01

Roč. 10, Jan 31 (2017), č. článku 16. ISSN 1662-5099 R&D Projects: GA ČR(CZ) GA15-15839S; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) EE2.3.30.0025 Institutional support: RVO:67985823 Keywords : TRP channel * S1-S2 linker * allyl isothiocynate * sensor module Subject RIV: FH - Neurology OBOR OECD: Neuroscience s (including psychophysiology Impact factor: 5.076, year: 2016

TU-H-CAMPUS-JeP2-05: Can Automatic Delineation of Cardiac Substructures On Noncontrast CT Be Used for Cardiac Toxicity Analysis?

Energy Technology Data Exchange (ETDEWEB)

Luo, Y; Liao, Z; Jiang, W; Gomez, D; Williamson, R; Court, L; Yang, J [MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose: To evaluate the feasibility of using an automatic segmentation tool to delineate cardiac substructures from computed tomography (CT) images for cardiac toxicity analysis for non-small cell lung cancer (NSCLC) patients after radiotherapy. Methods: A multi-atlas segmentation tool developed in-house was used to delineate eleven cardiac substructures including the whole heart, four heart chambers, and six greater vessels automatically from the averaged 4DCT planning images for 49 NSCLC patients. The automatic segmented contours were edited appropriately by two experienced radiation oncologists. The modified contours were compared with the auto-segmented contours using Dice similarity coefficient (DSC) and mean surface distance (MSD) to evaluate how much modification was needed. In addition, the dose volume histogram (DVH) of the modified contours were compared with that of the auto-segmented contours to evaluate the dosimetric difference between modified and auto-segmented contours. Results: Of the eleven structures, the averaged DSC values ranged from 0.73 ± 0.08 to 0.95 ± 0.04 and the averaged MSD values ranged from 1.3 ± 0.6 mm to 2.9 ± 5.1mm for the 49 patients. Overall, the modification is small. The pulmonary vein (PV) and the inferior vena cava required the most modifications. The V30 (volume receiving 30 Gy or above) for the whole heart and the mean dose to the whole heart and four heart chambers did not show statistically significant difference between modified and auto-segmented contours. The maximum dose to the greater vessels did not show statistically significant difference except for the PV. Conclusion: The automatic segmentation of the cardiac substructures did not require substantial modification. The dosimetric evaluation showed no statistically significant difference between auto-segmented and modified contours except for the PV, which suggests that auto-segmented contours for the cardiac dose response study are feasible in the clinical

TU-H-CAMPUS-JeP2-05: Can Automatic Delineation of Cardiac Substructures On Noncontrast CT Be Used for Cardiac Toxicity Analysis?

International Nuclear Information System (INIS)

Luo, Y; Liao, Z; Jiang, W; Gomez, D; Williamson, R; Court, L; Yang, J

2016-01-01

Purpose: To evaluate the feasibility of using an automatic segmentation tool to delineate cardiac substructures from computed tomography (CT) images for cardiac toxicity analysis for non-small cell lung cancer (NSCLC) patients after radiotherapy. Methods: A multi-atlas segmentation tool developed in-house was used to delineate eleven cardiac substructures including the whole heart, four heart chambers, and six greater vessels automatically from the averaged 4DCT planning images for 49 NSCLC patients. The automatic segmented contours were edited appropriately by two experienced radiation oncologists. The modified contours were compared with the auto-segmented contours using Dice similarity coefficient (DSC) and mean surface distance (MSD) to evaluate how much modification was needed. In addition, the dose volume histogram (DVH) of the modified contours were compared with that of the auto-segmented contours to evaluate the dosimetric difference between modified and auto-segmented contours. Results: Of the eleven structures, the averaged DSC values ranged from 0.73 ± 0.08 to 0.95 ± 0.04 and the averaged MSD values ranged from 1.3 ± 0.6 mm to 2.9 ± 5.1mm for the 49 patients. Overall, the modification is small. The pulmonary vein (PV) and the inferior vena cava required the most modifications. The V30 (volume receiving 30 Gy or above) for the whole heart and the mean dose to the whole heart and four heart chambers did not show statistically significant difference between modified and auto-segmented contours. The maximum dose to the greater vessels did not show statistically significant difference except for the PV. Conclusion: The automatic segmentation of the cardiac substructures did not require substantial modification. The dosimetric evaluation showed no statistically significant difference between auto-segmented and modified contours except for the PV, which suggests that auto-segmented contours for the cardiac dose response study are feasible in the clinical

Correlation of substructure with mechanical properties of plastically deformed reactor structural materials. Progress report, January 1, 1974--December 31, 1975

International Nuclear Information System (INIS)

Moteff, J.

1976-01-01

Ratio of the subgrain boundary dislocations to those contributing to creep deformation was found to be independent of applied stress and creep strain after the steady-state creep stage is reached. The observed cell or subgrain sizes are correlated with flow stress in Type 304 ss, and the deformation rate-stress relation obeys the equation epsilon =β lambda 3 (sigma/sub T//E)/sub n/ exp (-Q/sub c//RT), where lambda = subgrain size, sigma/sub T/ = effective true stress, E = Young modulus, and Q/sub c/ = 85 kcal/mole. Well-developed subgrains were observed in TEM on 304 ss tested in creep at 704 0 C. Role of twin boundary-grain boundary intersections in microcracking behavior of 304 ss deformed in slow tension and creep at 650 0 C was investigated. Grain shape analysis show that intragranular deformation becomes more predominant in the grains with the larger intercept distances, and that grain boundary sliding becomes important as the strain rate decreases. RT mechanical properties of austenitic ss are enhanced by subgrains formed during high-temperature deformation. The substructural development during high-temperature low-cycle fatigue of 304 ss was studied using TEM. Fatigue properties of Incoloy 800 tested in bend and push-pull modes are being compared. Effects of hold time on fatigue substructure and fracture of 304 ss are being studied. 31 figures, 53 references

Nonlinear seismic response analysis of embedded reactor buildings based on the substructure approach in time domain

International Nuclear Information System (INIS)

Hasegawa, M.; Nakai, S.; Watanabe, T.

1985-01-01

A practical method for elasto-plastic seismic response analysis is described under considerations of nonlinear material law of a structure and dynamic soil-structure interaction. The method is essentially based on the substructure approach of time domain analysis. Verification of the present method is carried out for typical BWR-MARK II type reactor building which is embedded in a soil, and the results are compared with those of the frequency response analysis which gives good accuracy for linear system. As a result, the present method exhibits sufficient accuracy. Furthermore, elasto-plastic analyses considering the soil-structure interaction are made as an application of the present method, and nonlinear behaviors of the structure and embedment effects are discussed. (orig.)

Effect of the shades of background substructures on the overall color of zirconia-based all-ceramic crowns

Science.gov (United States)

Tulapornchai, Chantana; Mamani, Jatuphol; Kamchatphai, Wannaporn; Thongpun, Noparat

2013-01-01

PURPOSE The objective of this study was to determine the effect of the color of a background substructure on the overall color of a zirconia-based all-ceramic crown. MATERIALS AND METHODS Twenty one posterior zirconia crowns were made for twenty subjects. Seven premolar crowns and six molar crowns were cemented onto abutments with metal post and core in the first and second group. In the third group, eight molar crowns were cemented onto abutments with a prefabricated post and composite core build-up. The color measurements of all-ceramic crowns were made before try-in, before and after cementation. A repeated measure ANOVA was used for a statistical analysis of a color change of all-ceramic crowns at α=.05. Twenty four zirconia specimens, with different core thicknesses (0.4-1 mm) were also prepared to obtain the contrast ratio of zirconia materials after veneering. RESULTS L*, a*, and b* values of all-ceramic crowns cemented either on a metal cast post and core or on a prefabricated post did not show significant changes (P>.05). However, the slight color changes of zirconia crowns were detected and represented by ΔE*ab values, ranging from 1.2 to 3.1. The contrast ratios of zirconia specimens were 0.92-0.95 after veneering. CONCLUSION No significant differences were observed between the L*, a*, and b* values of zirconia crowns cemented either on a metal cast post and core or a prefabricated post and composite core. However, the color of a background substructure could affect the overall color of posterior zirconia restorations with clinically recommended core thickness according to ΔE*ab values. PMID:24049574

Effect of the Linker in Terephthalate-Functionalized Conducting Redox Polymers

International Nuclear Information System (INIS)

Yang, Li; Huang, Xiao; Gogoll, Adolf; Strømme, Maria; Sjödin, Martin

2016-01-01

The combination of high capacity redox active pendent groups and conducting polymers, realized in conducting redox polymers (CRPs), provides materials with high charge storage capacity that are electronically conducting which makes CRPs attractive for electrical energy storage applications. In this report, six polythiophene and poly(3,4-ethylenedioxythiophene)(PEDOT)-based CRPs with a diethyl terephthalate unit covalently bound to the polymer chain by various linkers have been synthesized and characterized electrochemically. The effects of the choice of polymer backbone and of the nature of the link on the electrochemistry, and in particular the cycling stability of these polymers, are discussed. All CRPs show both the doping of the polymer backbone as well as the redox behavior of the pendent groups and the redox potential of the pendent groups in the CRPs is close to that of corresponding monomer, indicating insignificant interaction between the pendant and the polymer backbone. While all CRPs show various degrees of charge decay upon electrochemical redox conversion, the PEDOT-based CRPs show significantly improved stability compared to the polythiophene counterparts. Moreover, we show that by the right choice of link the cycling stability of diethyl terephthalate substituted PEDOT-based CRPs can be significantly improved.

Dissociation Behavior of a TEMPO-Active Ester Cross-Linker for Peptide Structure Analysis by Free Radical Initiated Peptide Sequencing (FRIPS) in Negative ESI-MS.

Science.gov (United States)

Hage, Christoph; Ihling, Christian H; Götze, Michael; Schäfer, Mathias; Sinz, Andrea

2017-01-01

We have synthesized a homobifunctional amine-reactive cross-linking reagent, containing a TEMPO (2,2,6,6-tetramethylpiperidine-1-oxy) and a benzyl group (Bz), termed TEMPO-Bz-linker, to derive three-dimensional structural information of proteins. The aim for designing this novel cross-linker was to facilitate the mass spectrometric analysis of cross-linked products by free radical initiated peptide sequencing (FRIPS). In an initial study, we had investigated the fragmentation behavior of TEMPO-Bz-derivatized peptides upon collision activation in (+)-electrospray ionization collision-induced dissociation tandem mass spectrometry (ESI-CID-MS/MS) experiments. In addition to the homolytic NO-C bond cleavage FRIPS pathway delivering the desired odd-electron product ions, an alternative heterolytic NO-C bond cleavage, resulting in even-electron product ions mechanism was found to be relevant. The latter fragmentation route clearly depends on the protonation of the TEMPO-Bz-moiety itself, which motivated us to conduct (-)-ESI-MS, CID-MS/MS, and MS 3 experiments of TEMPO-Bz-cross-linked peptides to further clarify the fragmentation behavior of TEMPO-Bz-peptide molecular ions. We show that the TEMPO-Bz-linker is highly beneficial for conducting FRIPS in negative ionization mode as the desired homolytic cleavage of the NO-C bond is the major fragmentation pathway. Based on characteristic fragments, the isomeric amino acids leucine and isoleucine could be discriminated. Interestingly, we observed pronounced amino acid side chain losses in cross-linked peptides if the cross-linked peptides contain a high number of acidic amino acids. Graphical Abstract ᅟ.

Exploring a heavy charged Higgs using jet substructure in a fully hadronic channel

Directory of Open Access Journals (Sweden)

Riley Patrick

2017-04-01

Full Text Available In the framework of the type-II Two Higgs Doublet Model (2HDM-II a charged Higgs search strategy is presented for the dominant production mode gb→tH± at the 14 TeV LHC. We consider the decay process which includes t→bW± and H±→AW±, and a fully hadronic final state consisting of bbb¯+jets+X. Dictated by the b→sγ constraints which render MH±>480 GeV we study two scenarios in which the charged Higgs mass is 750 GeV and the pseudoscalar Higgs mass is 200 GeV and 500 GeV. In this mass scheme highly boosted final state objects are expected and handled with jet substructure techniques which also acts to suppress the standard model background. A detailed detector analysis is performed, followed by a multivariate analysis involving many kinematic variables to optimize signal to background significance. Finally the LHC search sensitivities for the two scenarios are presented for various integrated luminosities.

Effects of the amino acid linkers on the melanoma-targeting and pharmacokinetic properties of 111In-labeled lactam bridge-cyclized alpha-MSH peptides.

Science.gov (United States)

Guo, Haixun; Yang, Jianquan; Gallazzi, Fabio; Miao, Yubin

2011-04-01

The purpose of this study was to examine the profound effects of the amino acid linkers on the melanoma-targeting and pharmacokinetic properties of (111)In-labeled lactam bridge-cyclized DOTA-[X]-CycMSH(hex) {1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[X]-c[Asp-His-dPhe-Arg-Trp-Lys]-CONH(2); X = GGNle, GENle, or NleGE; GG = -Gly-Gly- and GE = -Gly-Glu-} peptides. Three novel peptides (DOTA-GGNle-CycMSH(hex), DOTA-GENle-CycMSH(hex), and DOTA-NleGE-CycMSH(hex)) were designed and synthesized. The melanocortin-1 (MC1) receptor-binding affinities of the peptides were determined in B16/F1 melanoma cells. The melanoma-targeting and pharmacokinetic properties of (111)In-DOTA-GGNle-CycMSH(hex) and (111)In-DOTA-GENle-CycMSH(hex) were determined in B16/F1 melanoma-bearing C57 mice. DOTA-GGNle-CycMSH(hex) and DOTA-GENle-CycMSH(hex) displayed 2.1 and 11.5 nM MC1 receptor-binding affinities, whereas DOTA-NleGE-CycMSH(hex) showed 873.4 nM MC1 receptor-binding affinity. The introduction of the -GG- linker maintained high melanoma uptake while decreasing kidney and liver uptake of (111)In-DOTA-GGNle-CycMSH(hex). The tumor uptake of (111)In-DOTA-GGNle-CycMSH(hex) was 19.05 ± 5.04 and 18.6 ± 3.56 percentage injected dose per gram at 2 and 4 h after injection, respectively. (111)In-DOTA-GGNle-CycMSH(hex) exhibited 28%, 32%, and 42% less kidney uptake than (111)In-DOTA-Nle-CycMSH(hex) we reported previously, and 61%, 65%, and 68% less liver uptake than (111)In-DOTA-Nle-CycMSH(hex) at 2, 4, and 24 h after injection, respectively. The amino acid linkers exhibited profound effects on the melanoma-targeting and pharmacokinetic properties of the (111)In-labeled lactam bridge-cyclized α-melanocyte-stimulating hormone peptides. Introduction of the -GG- linker maintained high melanoma uptake while reducing kidney and liver uptake of (111)In-DOTA-GGNle-CycMSH(hex), highlighting its potential as an effective imaging probe for melanoma detection, as well as a therapeutic peptide

Substructure method in high-speed monorail dynamic problems

Science.gov (United States)

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

Eviction of linker histone H1 by NAP-family histone chaperones enhances activated transcription.

Science.gov (United States)

Zhang, Qian; Giebler, Holli A; Isaacson, Marisa K; Nyborg, Jennifer K

2015-01-01

In the Metazoan nucleus, core histones assemble the genomic DNA to form nucleosome arrays, which are further compacted into dense chromatin structures by the linker histone H1. The extraordinary density of chromatin creates an obstacle for accessing the genetic information. Regulation of chromatin dynamics is therefore critical to cellular homeostasis, and histone chaperones serve as prominent players in these processes. In the current study, we examined the role of specific histone chaperones in negotiating the inherently repressive chromatin structure during transcriptional activation. Using a model promoter, we demonstrate that the human nucleosome assembly protein family members hNap1 and SET/Taf1β stimulate transcription in vitro during pre-initiation complex formation, prior to elongation. This stimulatory effect is dependent upon the presence of activators, p300, and Acetyl-CoA. We show that transcription from our chromatin template is strongly repressed by H1, and that both histone chaperones enhance RNA synthesis by overcoming H1-induced repression. Importantly, both hNap1 and SET/Taf1β directly bind H1, and function to enhance transcription by evicting the linker histone from chromatin reconstituted with H1. In vivo studies demonstrate that SET/Taf1β, but not hNap1, strongly stimulates activated transcription from the chromosomally-integrated model promoter, consistent with the observation that SET/Taf1β is nuclear, whereas hNap1 is primarily cytoplasmic. Together, these observations indicate that SET/Taf1β may serve as a critical regulator of H1 dynamics and gene activation in vivo. These studies uncover a novel function for SET that mechanistically couples transcriptional derepression with H1 dynamics. Furthermore, they underscore the significance of chaperone-dependent H1 displacement as an essential early step in the transition of a promoter from a dense chromatin state into one that is permissive to transcription factor binding and robust

Cytoskeletal Linker Protein Dystonin Is Not Critical to Terminal Oligodendrocyte Differentiation or CNS Myelination.

Directory of Open Access Journals (Sweden)

Samantha F Kornfeld

Full Text Available Oligodendrocyte differentiation and central nervous system myelination require massive reorganization of the oligodendrocyte cytoskeleton. Loss of specific actin- and tubulin-organizing factors can lead to impaired morphological and/or molecular differentiation of oligodendrocytes, resulting in a subsequent loss of myelination. Dystonin is a cytoskeletal linker protein with both actin- and tubulin-binding domains. Loss of function of this protein results in a sensory neuropathy called Hereditary Sensory Autonomic Neuropathy VI in humans and dystonia musculorum in mice. This disease presents with severe ataxia, dystonic muscle and is ultimately fatal early in life. While loss of the neuronal isoforms of dystonin primarily leads to sensory neuron degeneration, it has also been shown that peripheral myelination is compromised due to intrinsic Schwann cell differentiation abnormalities. The role of this cytoskeletal linker in oligodendrocytes, however, remains unclear. We sought to determine the effects of the loss of neuronal dystonin on oligodendrocyte differentiation and central myelination. To address this, primary oligodendrocytes were isolated from a severe model of dystonia musculorum, Dstdt-27J, and assessed for morphological and molecular differentiation capacity. No defects could be discerned in the differentiation of Dstdt-27J oligodendrocytes relative to oligodendrocytes from wild-type littermates. Survival was also compared between Dstdt-27J and wild-type oligodendrocytes, revealing no significant difference. Using a recently developed migration assay, we further analysed the ability of primary oligodendrocyte progenitor cell motility, and found that Dstdt-27J oligodendrocyte progenitor cells were able to migrate normally. Finally, in vivo analysis of oligodendrocyte myelination was done in phenotype-stage optic nerve, cerebral cortex and spinal cord. The density of myelinated axons and g-ratios of Dstdt-27J optic nerves was normal, as

Diols and anions can control the formation of an exciplex between a pyridinium boronic acid with an aryl group connected via a propylene linker.

Science.gov (United States)

Huang, Yan-Jun; Jiang, Yun-Bao; Bull, Steven D; Fossey, John S; James, Tony D

2010-11-21

The exciplex formation between a pyridinium boronic acid and phenyl group connected via a propylene linker can be monitored using fluorescence. Addition of pinacol affords a cyclic boronate ester with enhanced Lewis acidity that increases the strength of its cation-π stacking interaction causing a four-fold fluorescence enhancement.

Nonlinear seismic response analysis of an embedded reactor building based on the substructure approach

International Nuclear Information System (INIS)

Hasegawa, M.; Ichikawa, T.; Nakai, S.; Watanabe, T.

1987-01-01

A practical method to calculate the elasto-plastic seismic response of structures considering the dynamic soil-structure interaction is presented. The substructure technique in the time domain is utilized in the proposed method. A simple soil spring system with the coupling effects which are usually evaluated by the impedance matrix is introduced to consider the soil-structure interaction for embedded structures. As a numerical example, the response of a BWR-MARK II type reactor building embedded in the layered soil is calculated. The accuracy of the present method is verified by comparing its numerical results with exact solutions. The nonlinear behaivor and the soil-structure interaction effects on the response of the reactor building are also discussed in detail. It is concluded that the present method is effective for the aseismic design considering both the material nonlinearity of the nuclear reactor building and the dynamic soil-structure interaction. (orig.)

Synthetic surfactant- and cross-linker-free preparation of highly stable lipid-polymer hybrid nanoparticles as potential oral delivery vehicles.

Science.gov (United States)

Wang, Taoran; Xue, Jingyi; Hu, Qiaobin; Zhou, Mingyong; Chang, Chao; Luo, Yangchao

2017-06-05

The toxicity associated with concentrated synthetic surfactants and the poor stability at gastrointestinal condition are two major constraints for practical applications of solid lipid nanoparticles (SLN) as oral delivery vehicles. In this study, a synthetic surfactant-free and cross-linker-free method was developed to fabricate effective, safe, and ultra-stable lipid-polymer hybrid nanoparticles (LPN). Bovine serum albumin (BSA) and dextran varying in molecular weights were first conjugated through Maillard reaction and the conjugates were exploited to emulsify solid lipid by a solvent diffusion and sonication method. The multilayer structure was formed by self-assembly of BSA-dextran micelles to envelope solid lipid via a pH- and heating-induced facile process with simultaneous surface deposition of pectin. The efficiency of different BSA-dextran conjugates was systematically studied to prepare LPN with the smallest size, the most homogeneous distribution and the greatest stability. The molecular interactions were characterized by Fourier transform infrared and fluorescence spectroscopies. Both nano spray drying and freeze-drying methods were tested to produce spherical and uniform pectin-coated LPN powders that were able to re-assemble nanoscale structure when redispersed in water. The results demonstrated the promise of a synthetic surfactant- and cross-linker-free technique to prepare highly stable pectin-coated LPN from all natural biomaterials as potential oral delivery vehicles.

Wall to membrane linkers, stretch activated channels, and the detection of tension, voltage, temperature, auxin, and pH

Science.gov (United States)

Pickard, B. G.

1992-01-01

Introduction. The higher plant is a heterogeneous, mechanically prestressed structure continually subject to shifting forces. When a cell grows in a plant at gravitropic equilibrium, it must create localized maxima of shear in walls of neighboring cells. Such mechanical stress and strain are likely detected in a variety of ways. However, tension-sensitive ion channels are of particular interest because it appears that they are elaborately evolved for sensory function. We hypothesize that 1) the patchy patterns of high shear are focused via wall-to-membrane linkers onto the plasma membrane, where 2) they are translated by mechanosensory cation channels into corresponding patterns of high cytosolic Ca2+, which 3) initiate local enhancement of wall expansion. Further, we hypothesize that the local promotion of enhancement is achieved at least in part by local intensification of auxin transport across the plasma membrane. By implication, when an organ is asymmetrically pressed, rubbed, or bent or when it is displaced in the gravitational field, the net asymmetry of shear stress occurring across the organ would lead to asymmetric redistribution of auxin and corrective asymmetric growth. We shall describe a representative mechanosensitive Ca(2+) -selective cation channel (MCaC) with susceptibilities to xenobiotics implicating it as a force transducer in thigmo- and gravitropism. Then, we shall consider whether a putative wall-to-membrane linker (WML) could be a key feature of the molecular architecture permitting the stress distributed in the wall system to be focused on the channels.

DSF: A Common Platform for Distributed Systems Research and Development

Science.gov (United States)

Tang, Chunqiang

This paper presents Distributed Systems Foundation (DSF), a common platform for distributed systems research and development. It can run a distributed algorithm written in Java under multiple execution modes—simulation, massive multi-tenancy, and real deployment. DSF provides a set of novel features to facilitate testing and debugging, including chaotic timing test and time travel debugging with mutable replay. Unlike existing research prototypes that offer advanced debugging features by hacking programming tools, DSF is written entirely in Java, without modifications to any external tools such as JVM, Java runtime library, compiler, linker, system library, OS, or hypervisor. This simplicity stems from our goal of making DSF not only a research prototype but more importantly a production tool. Experiments show that DSF is efficient and easy to use. DSF's massive multi-tenancy mode can run 4,000 OS-level threads in a single JVM to concurrently execute (as opposed to simulate) 1,000 DHT nodes in real-time.

Particel substructure. A common theme of discovery in this century

International Nuclear Information System (INIS)

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

Discovering Higgs Bosons of the MSSM using Jet Substructure

International Nuclear Information System (INIS)

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

2010-01-01

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 # tilde q#,m # tilde g# > m # tilde W#, # tilde B# > m h + μ; m(tilde q);m # tilde q#,m # tilde g# > m # tilde W#, # tilde B# > m h,H,A + μ; and m # tilde q#,m # tilde g# > m # tilde W# > m h + μ with m # tilde B# ∼ μ. 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 -1 of 14 TeV LHC data, with m # tilde q# ∼< 1 TeV, and one of the above superpartner mass hierarchies, our estimate of S√ 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.

Discovering Higgs bosons of the MSSM using jet substructure

International Nuclear Information System (INIS)

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

2010-01-01

We present a qualitatively new approach to discover Higgs bosons of the minimal supersymmetric standard model (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 bb throughout the entire parameter space, while the heavier neutral Higgs bosons, if light enough to be produced in a cascade, also predominantly decay to bb. 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 q -tilde, m g -tilde>m W -tilde ,B -tilde>m h +μ; m q -tilde, m g -tilde>m W -tilde ,B -tilde>m h,H,A +μ; and m q -tilde, m g -tilde>m W -tilde>m h +μ with m B -tilde≅μ. In these cascades, the Higgs bosons are boosted, with p T >200 GeV a large fraction of the time. Since Higgses appear in cascades originating from squarks and/or gluinos, the cross section for events with at least one Higgs can be the same order as squark/gluino production. Given 10 fb -1 of 14 TeV LHC data, with m q -tilde < or approx. 1 TeV, and one of the above superpartner mass hierarchies, our estimate of S/√(B) of the Higgs signal is sufficiently high that the bb mode can become the discovery mode of the lightest Higgs boson of the MSSM.

Revealing the importance of linkers in K-series oxime reactivators for tabun-inhibited AChE using quantum chemical, docking and SMD studies.

Science.gov (United States)

Ghosh, Shibaji; Chandar, Nellore Bhanu; Jana, Kalyanashis; Ganguly, Bishwajit

2017-08-01

Inhibition of acetylcholinesterase (AChE) with organophosphorus compounds has a detrimental effect on human life. Oxime K203 seems to be one of the promising reactivators for tabun-inhibited AChE than (K027, K127, and K628). These reactivators differ only in the linker units between the two pyridinium rings. The conformational analyses performed with quantum chemical RHF/6-31G* level for K027, K127, K203 and K628 showed that the minimum energy conformers have different orientations of the active and peripheral pyridinium rings for these reactivator molecules. K203 with (-CH 2 -CH=CH-CH 2 -) linker unit possesses more open conformation compared to the other reactivators. Such orientation of K203 experiences favorable interaction with the surrounding residues of catalytic anionic site (CAS) and peripheral anionic site (PAS) of tabun-inhibited AChE. From the steered molecular dynamics simulations, it has been observed that the oxygen atom of the oxime group of K203 reactivator approaches nearest to the P-atom of the SUN203 (3.75 Å) at lower time scales (less than ~1000 ps) as compared to the other reactivators. K203 experiences less number of hydrophobic interaction with the PAS residues which is suggested to be an important factor for the efficient reactivation process. In addition, K203 crates large number of H-bonding with CAS residues SUN203, Phe295, Tyr337, Phe338 and His447. K203 barely changes its conformation during the SMD simulation process and hence the energy penalty to adopt any other conformation is minimal in this case as compared to the other reactivators. The molecular mechanics and Poisson-Boltzmann surface area binding energies obtained for the interaction of K203 inside the gorge of tabun inhibited AChE is substantially higher (-290.2 kcal/mol) than the corresponding K628 reactivator (-260.4 kcal/mol), which also possess unsaturated aromatic linker unit.

Revealing the importance of linkers in K-series oxime reactivators for tabun-inhibited AChE using quantum chemical, docking and SMD studies

Science.gov (United States)

Ghosh, Shibaji; Chandar, Nellore Bhanu; Jana, Kalyanashis; Ganguly, Bishwajit

2017-08-01

Inhibition of acetylcholinesterase (AChE) with organophosphorus compounds has a detrimental effect on human life. Oxime K203 seems to be one of the promising reactivators for tabun-inhibited AChE than (K027, K127, and K628). These reactivators differ only in the linker units between the two pyridinium rings. The conformational analyses performed with quantum chemical RHF/6-31G* level for K027, K127, K203 and K628 showed that the minimum energy conformers have different orientations of the active and peripheral pyridinium rings for these reactivator molecules. K203 with (-CH2-CH=CH-CH2-) linker unit possesses more open conformation compared to the other reactivators. Such orientation of K203 experiences favorable interaction with the surrounding residues of catalytic anionic site (CAS) and peripheral anionic site (PAS) of tabun-inhibited AChE. From the steered molecular dynamics simulations, it has been observed that the oxygen atom of the oxime group of K203 reactivator approaches nearest to the P-atom of the SUN203 (3.75 Å) at lower time scales (less than 1000 ps) as compared to the other reactivators. K203 experiences less number of hydrophobic interaction with the PAS residues which is suggested to be an important factor for the efficient reactivation process. In addition, K203 crates large number of H-bonding with CAS residues SUN203, Phe295, Tyr337, Phe338 and His447. K203 barely changes its conformation during the SMD simulation process and hence the energy penalty to adopt any other conformation is minimal in this case as compared to the other reactivators. The molecular mechanics and Poisson-Boltzmann surface area binding energies obtained for the interaction of K203 inside the gorge of tabun inhibited AChE is substantially higher (-290.2 kcal/mol) than the corresponding K628 reactivator (-260.4 kcal/mol), which also possess unsaturated aromatic linker unit.

Efficient loading of primary alcohols onto a solid phase using a trityl bromide linker

DEFF Research Database (Denmark)

Crestey, François; Ottesen, Lars Korsgaard; Jaroszewski, Jerzy Witold

2008-01-01

The Letter describes an improved, rapid and mild strategy for the loading of primary alcohols onto a polystyrene trityl resin via a highly reactive trityl bromide linker. This protocol facilitates an efficient resin loading even of acid-sensitive or heat-labile alcohols, which otherwise require...... expensive or non-commercial resin types. Secondary alcohols were only attached in moderate to low yields, while attempts to load a tertiary alcohol expectedly failed. Importantly, selective attachment of diols via a primary alcohol group in the presence of more hindered alcohol groups proved possible....... The effects of activation time and reagent excess as well as alcohol structure were investigated. This improved method provides a convenient access to O-linked resin-bound N-Fmoc-protected amino alcohols that may be employed in SPS of peptides with C-terminal alcohol functionalities. In the case...

Effects of linker variation on the in vitro and in vivo characteristics of an 111In-labeled RGD peptide

International Nuclear Information System (INIS)

Dijkgraaf, Ingrid; Liu, Shuang; Kruijtzer, John A.W.; Soede, Annemieke C.; Oyen, Wim J.G.; Liskamp, Rob M.J.; Corstens, Frans H.M.; Boerman, Otto C.

2007-01-01

Introduction: Due to the selective expression of the α v β 3 integrin in tumors, radiolabeled arginine-glycine-aspartic acid (RGD) peptides are attractive candidates for tumor targeting. Minor modifications of these peptides could have a major impact on in vivo characteristics. In this study, we systematically investigated the effects of linker modification between two cyclic RGD sequences and DOTA (1,4,7,10-tetraazadodecane-N,N',N ' ,N'''-tetraacetic acid) on the in vitro and in vivo characteristics of the tracer. Methods: A dimeric RGD peptide was synthesized and conjugated either directly with DOTA or via different linkers: PEG 4 (polyethylene glycol), glutamic acid or lysine. The RGD peptides were radiolabeled with 111 In, and their in vitro and in vivo α v β 3 -binding characteristics were determined. Results: LogP values varied between -2.82±0.06 and -3.95±0.33. The IC 50 values for DOTA-E-[c(RGDfK)] 2 , DOTA-PEG 4 -E-[c(RGDfK)] 2 , DOTA-E-E-[c(RGDfK)] 2 and DOTA-K-E-[c(RGDfK)] 2 were comparable. Two hours after injection, the tumor uptakes of the 111 In-labeled compounds were not significantly different. The kidney accumulation of [ 111 In]-DOTA-K-E-[c(RGDfK)] 2 [4.05±0.20% of the injected dose per gram (ID/g)] was significantly higher as compared with that of [ 111 In]-DOTA-E-[c(RGDfK)] 2 (2.63±0.19% ID/g; P 111 In]-DOTA-E-E-[c(RGDfK)] 2 (2.16±0.21% ID/g; P 111 In]-DOTA-E-E-[c(RGDfK)] 2 (2.12±0.09% ID/g) was significantly higher as compared with that of [ 111 In]-DOTA-E-[c(RGDfK)] 2 (1.64±0.1% ID/g; P 111 In]-DOTA-K-E-[c(RGDfK)] 2 (1.52±0.04% ID/g; P v β 3 and tumor uptake. Insertion of lysine caused enhanced kidney retention; that of glutamic acid also resulted in enhanced retention in the kidneys. PEG 4 appeared to be the most suitable linker as compared with glutamic acid and lysine because it has the highest tumor-to-blood ratio and the lowest uptake in the kidney and liver

A Class of Rigid Linker-bearing Glucosides for Membrane Protein Structural Study.

Science.gov (United States)

Sadaf, Aiman; Mortensen, Jonas S; Capaldi, Stefano; Tikhonova, Elena; Hariharan, Parameswaran; de Castro Ribeiro, Orquidea; Loland, Claus J; Guan, Lan; Byrne, Bernadette; Chae, Pil Seok

2016-03-01

Membrane proteins are amphipathic bio-macromolecules incompatible with the polar environments of aqueous media. Conventional detergents encapsulate the hydrophobic surfaces of membrane proteins allowing them to exist in aqueous solution. Membrane proteins stabilized by detergent micelles are used for structural and functional analysis. Despite the availability of a large number of detergents, only a few agents are sufficiently effective at maintaining the integrity of membrane proteins to allow successful crystallization. In the present study, we describe a novel class of synthetic amphiphiles with a branched tail group and a triglucoside head group. These head and tail groups were connected via an amide or ether linkage by using a tris(hydroxylmethyl)aminomethane (TRIS) or neopentyl glycol (NPG) linker to produce TRIS-derived triglucosides (TDTs) and NPG-derived triglucosides (NDTs), respectively. Members of this class conferred enhanced stability on target membrane proteins compared to conventional detergents. Because of straightforward synthesis of the novel agents and their favourable effects on a range of membrane proteins, these agents should be of wide applicability to membrane protein science.

Assessing the adsorption selectivity of linker functionalized, moisture-stable metal-organic framework thin films by means of an environment-controlled quartz crystal microbalance.

Science.gov (United States)

Bétard, Angélique; Wannapaiboon, Suttipong; Fischer, Roland A

2012-11-04

The stepwise thin film deposition of the robust, hydrophobic [Zn(4)O(dmcapz)(3)](n) (dmcapz = 3,5-dimethyl-4-carboxy-pyrazolato) is reported. The adsorption of small organic probe molecules, including alkanols, toluene, aniline and xylenes, was monitored by an environment-controlled quartz crystal microbalance setup. The adsorption selectivity was tuned by introducing alkyl side chains in the dmcapz linker.

Funktionalisierte Linker für Metallorganische Gerüstverbindungen, deren postsynthetische Modifikation und polar markierte Schutzgruppen für terminale Alkine

OpenAIRE

Roy, Pascal

2011-01-01

Metal-organic frameworks (MOFs) form the class of porous materials with the highest surface areas. This characteristic property combined with the variability of both building blocks, the inorganic node and the organic linker, makes many scientists dream of materials with very special chemical, electronic, optic and/or magnetic properties. For individual applications both building blocks, but also possibly in the framework embedded guests, play a crucial role. This work describes the synthe...

PSR B0329+54: substructure in the scatter-broadened image discovered with RadioAstron on baselines up to 330 000 km

Science.gov (United States)

Popov, Mikhail V.; Bartel, Norbert; Gwinn, Carl R.; Johnson, Michael D.; Andrianov, Andrey; Fadeev, Evgeny; Joshi, Bhal Chandra; Kardashev, Nikolay; Karuppusamy, Ramesh; Kovalev, Yuri Y.; Kramer, Michael; Rudnitskiy, Alexey; Shishov, Vladimir; Smirnova, Tatiana; Soglasnov, Vladimir A.; Zensus, J. Anton

2017-02-01

We have resolved the scatter-broadened image of PSR B0329+54 and detected a substructure within it. These results are not influenced by any extended structure of a source but instead are directly attributed to the interstellar medium. We obtained these results at 324 MHz with the ground-space interferometer RadioAstron, which included the Space Radio Telescope, ground-based Westerbork Synthesis Radio Telescope and 64-m Kalyazin Radio Telescope on baseline projections up to 330 000 km in 2013 November 22 and 2014 January 1 to 2. At short 15 000 to 35 000 km ground-space baseline projections, the visibility amplitude decreases with baseline length, providing a direct measurement of the size of the scattering disc of 4.8 ± 0.8 mas. At longer baselines, no visibility detections from the scattering disc would be expected. However, significant detections were obtained with visibility amplitudes of 3 to 5 per cent of the maximum scattered around a mean and approximately constant up to 330 000 km. These visibilities reflect a substructure from scattering in the interstellar medium and offer a new probe of ionized interstellar material. The size of the diffraction spot near Earth is 17 000 ± 3 000 km. With the assumption of turbulent irregularities in the plasma of the interstellar medium, we estimate that the effective scattering screen is located 0.6 ± 0.1 of the distance from the Earth towards the pulsar.

The application of in-situ 3D X-ray diffraction in annealing experiments: First interpretation of substructure development in deformed NaCl

DEFF Research Database (Denmark)

Borthwick, Verity; Schmidt, Søren; Piazolo, Sandra

2012-01-01

In-situ 3D X-ray diffraction (3DXRD) annealing experiments were conducted at the ID-11 beamline at the European Synchrotron Radiation Facility in Grenoble. This allowed us to nondestructively document and subsequently analyse the development of substructures during heating, without the influence...... subgrain boundary formation. These results demonstrate that 3DXRD coupled with in-situ heating is a successful non-destructive technique for examining real-time postdeformational annealing in strongly deformed crystalline materials with complicated microstructures. © (2012) Trans Tech Publications...

Impact of Intragranular Substructure Parameters on the Forming Limit Diagrams of Single-Phase B.C.C. Steels

Directory of Open Access Journals (Sweden)

Gérald Franz

2013-11-01

Full Text Available An advanced elastic-plastic self-consistent polycrystalline model, accounting for intragranular microstructure development and evolution, is coupled with a bifurcation-based localization criterion and applied to the numerical investigation of the impact of microstructural patterns on ductility of single-phase steels. The proposed multiscale model, taking into account essential microstructural aspects, such as initial and induced textures, dislocation densities, and softening mechanisms, allows us to emphasize the relationship between intragranular microstructure of B.C.C. steels and their ductility. A qualitative study in terms of forming limit diagrams for various dislocation networks, during monotonic loading tests, is conducted in order to analyze the impact of intragranular substructure parameters on the formability of single-phase B.C.C. steels.

A highly conserved glycine within linker I and the extreme C terminus of G protein alpha subunits interact cooperatively in switching G protein-coupled receptor-to-effector specificity

DEFF Research Database (Denmark)

Kostenis, Evi; Martini, Lene; Ellis, James

2004-01-01

Numerous studies have attested to the importance of the extreme C terminus of G protein alpha subunits in determining their selectivity of receptor recognition. We have previously reported that a highly conserved glycine residue within linker I is important for constraining the fidelity of receptor...... recognition by Galpha(q) proteins. Herein, we explored whether both modules (linker I and extreme C terminus) interact cooperatively in switching G protein-coupled receptor (GPCR)-to-effector specificity and created as models mutant Galpha(q) proteins in which glycine was replaced with various amino acids...... and the C-terminal five Galpha(q) residues with the corresponding Galpha(i) or Galpha(s) sequence. Coupling properties of the mutated Galpha(q) proteins were determined after coexpression with a panel of 13 G(i)-and G(s) -selective receptors and compared with those of Galpha proteins modified in only one...

Micropatterning of biomolecules on a glass substrate in fused silica microchannels by using photolabile linker-based surface activation

International Nuclear Information System (INIS)

Jang, K.; Mawatari, K.; Kitamori, T.; Xu, Y.; Sato, K.; Tanaka, Y.

2012-01-01

We report on a straightforward method for creating micropatterns of multiple biomolecules. The anti-fouling agent 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer and a photolabile linker (PL) were covalently linked to an amino-terminated silane surface. Patterns were generated by selective removal of the MPC polymer via UV irradiation. Multiple micropatterns of fluorescein isothiocyanate (FITC)-labeled bovine serum albumin (BSA) and rhodamine-labeled goat fragment antigen-binding fragments (FAB) were deposited on a same glass substrate. We also employed micropatterning of multiple biomolecules in that Texas red-labeled BSA and FITC-labeled rabbit anti-mouse IgG were placed inside a microchannel. (author)

Superposed epoch study of ICME sub-structures near Earth and their effects on Galactic cosmic rays

Science.gov (United States)

Masías-Meza, J. J.; Dasso, S.; Démoulin, P.; Rodriguez, L.; Janvier, M.

2016-08-01

Context. Interplanetary coronal mass ejections (ICMEs) are the interplanetary manifestations of solar eruptions. The overtaken solar wind forms a sheath of compressed plasma at the front of ICMEs. Magnetic clouds (MCs) are a subset of ICMEs with specific properties (e.g. the presence of a flux rope). When ICMEs pass near Earth, ground observations indicate that the flux of Galactic cosmic rays (GCRs) decreases. Aims: The main aims of this paper are to find common plasma and magnetic properties of different ICME sub-structures and which ICME properties affect the flux of GCRs near Earth. Methods: We used a superposed epoch method applied to a large set of ICMEs observed in situ by the spacecraft ACE, between 1998 and 2006. We also applied a superposed epoch analysis on GCRs time series observed with the McMurdo neutron monitors. Results: We find that slow MCs at 1 AU have on average more massive sheaths. We conclude that this is because they are more effectively slowed down by drag during their travel from the Sun. Slow MCs also have a more symmetric magnetic field and sheaths expanding similarly as their following MC, while in contrast, fast MCs have an asymmetric magnetic profile and a sheath in compression. In all types of MCs, we find that the proton density and the temperature and the magnetic fluctuations can diffuse within the front of the MC due to 3D reconnection. Finally, we derive a quantitative model that describes the decrease in cosmic rays as a function of the amount of magnetic fluctuations and field strength. Conclusions: The obtained typical profiles of sheath, MC and GCR properties corresponding to slow, middle, and fast ICMEs, can be used for forecasting or modelling these events, and to better understand the transport of energetic particles in ICMEs. They are also useful for improving future operative space weather activities.

Jet substructure using semi-inclusive jet functions in SCET

International Nuclear Information System (INIS)

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

2016-01-01

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.

Reduction of fatigue loads on jacket substructure through blade design optimization for multimegawatt wind turbines at 50 m water depths

DEFF Research Database (Denmark)

NJOMO WANDJI, Wilfried; Pavese, Christian; Natarajan, Anand

2016-01-01

This paper addresses the reduction of the fore-aft damage equivalent moment at the tower base for multi-megawatt offshore wind turbines mounted on jacket type substructures at 50 m water depths. The study investigates blade design optimization of a reference 10 MW wind turbine under standard wind...... conditions of onshore sites. The blade geometry and structure is optimized to yield a design that minimizes tower base fatigue loads without significant loss of power production compared to that of the reference setup. The resulting blade design is then mounted on a turbine supported by a jacket and placed...

Crucial role of dynamic linker histone binding and divalent ions for DNA accessibility and gene regulation revealed by mesoscale modeling of oligonucleosomes

Science.gov (United States)

Collepardo-Guevara, Rosana; Schlick, Tamar

2012-01-01

Monte Carlo simulations of a mesoscale model of oligonucleosomes are analyzed to examine the role of dynamic-linker histone (LH) binding/unbinding in high monovalent salt with divalent ions, and to further interpret noted chromatin fiber softening by dynamic LH in monovalent salt conditions. We find that divalent ions produce a fiber stiffening effect that competes with, but does not overshadow, the dramatic softening triggered by dynamic-LH behavior. Indeed, we find that in typical in vivo conditions, dynamic-LH binding/unbinding reduces fiber stiffening dramatically (by a factor of almost 5, as measured by the elasticity modulus) compared with rigidly fixed LH, and also the force needed to initiate chromatin unfolding, making it consistent with those of molecular motors. Our data also show that, during unfolding, divalent ions together with LHs induce linker-DNA bending and DNA–DNA repulsion screening, which guarantee formation of heteromorphic superbeads-on-a-string structures that combine regions of loose and compact fiber independently of the characteristics of the LH–core bond. These structures might be important for gene regulation as they expose regions of the DNA selectively. Dynamic control of LH binding/unbinding, either globally or locally, in the presence of divalent ions, might constitute a mechanism for regulation of gene expression. PMID:22790986

Preferential 5-Methylcytosine Oxidation in the Linker Region of Reconstituted Positioned Nucleosomes by Tet1 Protein.

Science.gov (United States)

Kizaki, Seiichiro; Zou, Tingting; Li, Yue; Han, Yong-Woon; Suzuki, Yuki; Harada, Yoshie; Sugiyama, Hiroshi

2016-11-07

Tet (ten-eleven translocation) family proteins oxidize 5-methylcytosine (mC) to 5-hydroxymethylcytosine (hmC), 5-formylcytosine (fC), and 5-carboxycytosine (caC), and are suggested to be involved in the active DNA demethylation pathway. In this study, we reconstituted positioned mononucleosomes using CpG-methylated 382 bp DNA containing the Widom 601 sequence and recombinant histone octamer, and subjected the nucleosome to treatment with Tet1 protein. The sites of oxidized methylcytosine were identified by bisulfite sequencing. We found that, for the oxidation reaction, Tet1 protein prefers mCs located in the linker region of the nucleosome compared with those located in the core region. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Two-dimensional layer architecture assembled by Keggin polyoxotungstate, Cu(II)-EDTA complex and sodium linker: Synthesis, crystal structures, and magnetic properties

International Nuclear Information System (INIS)

Liu Hong; Xu Lin; Gao Guanggang; Li Fengyan; Yang Yanyan; Li Zhikui; Sun Yu

2007-01-01

Reaction of Keggin polyoxotungstate with copper(II)-EDTA (EDTA=ethylenediamine tetraacetate) complex under mild conditions led to the formation of hybrid inorganic-organic compounds Na 4 (OH)[(Cu 2 EDTA)PW 12 O 40 ].17H 2 O (1) and Na 4 [(Cu 2 EDTA)SiW 12 O 40 ].19H 2 O (2). The single-crystal X-ray diffraction analyses reveal their two structural features: (1) one-dimensional chain structure consisting of Keggin polyoxotungstate and copper(II)-EDTA complex; (2) Two-dimensional layer architecture assembled by the one-dimensional chain structure and sodium linker. The results of magnetic measurements in the temperature range 300-2 K indicated the existence of ferromagnetic exchange interactions between the Cu II ions for both compounds. In addition, TGA analysis, IR spectra, and electrochemical properties were also investigated to well characterize these two compounds. - Graphical abstract: Two new polyoxometalate-based hybrids, Na 4 (OH)[Cu 2 (EDTA)PW 12 O 40 ].17H 2 O (1) and Na 4 [Cu 2 (EDTA)SiW 12 O 40 ].19H 2 O (2), have been synthesized and structurally characterized, which consist of one-dimensional chain structure assembled by Keggin polyoxotungstate and copper(II)-EDTA complex. The chains are further connected to form two-dimensional layer architecture assembled by the one-dimensional chain structure and sodium linker

Mutation of Gly717Phe in human topoisomerase 1B has an effect on enzymatic function, reactivity to the camptothecin anticancer drug and on the linker domain orientation

DEFF Research Database (Denmark)

Wang, Zhenxing; D'Annessa, Ilda; Tesauro, Cinzia

2015-01-01

–DNA covalent adduct. In this work the role of the Gly717 residue, located in a α-helix structure bridging the active site and the linker domain, has been investigated mutating it in Phe. The mutation gives rise to drug resistance in vivo as observed through a viability assay of yeast cells. In vitro activity...... assays show that the mutant is characterized by a fast religation rate, only partially reduced by the presence of the drug. Comparative molecular dynamics simulations of the native and mutant proteins indicate that the mutation of Gly717 affects the motion orientation of the linker domain, changing its...... interaction with the DNA substrate, likely affecting the strand rotation and religation rate. The mutation also causes a slight rearrangement of the active site and of the drug binding site, providing an additional explanation for the lowered effect of camptothecin toward the mutant....

Evaluation and comparison of the marginal adaptation of two different substructure materials.

Science.gov (United States)

Karaman, Tahir; Ulku, Sabiha Zelal; Zengingul, Ali Ihsan; Guven, Sedat; Eratilla, Veysel; Sumer, Ebru

2015-06-01

In this study, we aimed to evaluate the amount of marginal gap with two different substructure materials using identical margin preparations. Twenty stainless steel models with a chamfer were prepared with a CNC device. Marginal gap measurements of the galvano copings on these stainless steel models and Co-Cr copings obtained by a laser-sintering method were made with a stereomicroscope device before and after the cementation process and surface properties were evaluated by scanning electron microscopy (SEM). A dependent t-test was used to compare the mean of the two groups for normally distributed data, and two-way variance analysis was used for more than two data sets. Pearson's correlation analysis was also performed to assess relationships between variables. According to the results obtained, the marginal gap in the galvano copings before cementation was measured as, on average, 24.47 ± 5.82 µm before and 35.11 ± 6.52 µm after cementation; in the laser-sintered Co-Cr structure, it was, on average, 60.45 ± 8.87 µm before and 69.33 ± 9.03 µm after cementation. A highly significant difference (Pcementation were within the clinically acceptable level. The smallest marginal gaps occurred with the use of galvano copings.

On the sound insulation of acoustic metasurface using a sub-structuring approach

Science.gov (United States)

Yu, Xiang; Lu, Zhenbo; Cheng, Li; Cui, Fangsen

2017-08-01

The feasibility of using an acoustic metasurface (AMS) with acoustic stop-band property to realize sound insulation with ventilation function is investigated. An efficient numerical approach is proposed to evaluate its sound insulation performance. The AMS is excited by a reverberant sound source and the standardized sound reduction index (SRI) is numerically investigated. To facilitate the modeling, the coupling between the AMS and the adjacent acoustic fields is formulated using a sub-structuring approach. A modal based formulation is applied to both the source and receiving room, enabling an efficient calculation in the frequency range from 125 Hz to 2000 Hz. The sound pressures and the velocities at the interface are matched by using a transfer function relation based on ;patches;. For illustration purposes, numerical examples are investigated using the proposed approach. The unit cell constituting the AMS is constructed in the shape of a thin acoustic chamber with tailored inner structures, whose stop-band property is numerically analyzed and experimentally demonstrated. The AMS is shown to provide effective sound insulation of over 30 dB in the stop-band frequencies from 600 to 1600 Hz. It is also shown that the proposed approach has the potential to be applied to a broad range of AMS studies and optimization problems.

The effect of linker of electrodes prepared from sol–gel ionic liquid precursor and carbon nanoparticles on dioxygen electroreduction bioelectrocatalysis

International Nuclear Information System (INIS)

Szot, Katarzyna; Lynch, Robert P.; Lesniewski, Adam; Majewska, Ewa; Sirieix-Plenet, Juliette; Gaillon, Laurent; Opallo, Marcin

2011-01-01

The effect of linker of three-dimensional, hydrophilic-carbon-nanoparticle film-electrodes prepared by layer-by-layer method on redox probe accumulation and bioelectrocatalytic dioxygen reduction was studied and compared for two different electrode scaffolds. The linker in both of these scaffolds was based on the same ionic liquid sol–gel precursor, 1-methyl-3-(3-trimethoxysilylpropyl) imidazolium bis(trifluoromethyl-sulfonyl)imide. The first electrode type was prepared by alternative immersion of tin doped indium oxide substrate in an aqueous suspension of carbon nanoparticles modified with phenyl sulphonic groups and a sol composed of ionic liquid sol–gel precursor and tetramethoxysilane. For the second electrode type sol was replaced by a methanolic suspension of silicate submicroparticles with appended imidazolium functional groups. In both films 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) anions accumulate irreversibly. In the case of the first electrode electrostatic attraction plays the more important role in comparison to the case of the second where stable adsorption of the redox probe takes place. After adsorption of bilirubin oxidase, electrodes obtained from sol and carbon nanoparticles exhibit modest bioelectrocatalytic activity towards dioxygen reduction at pH 4.8, however those obtained from oppositely charged particles are much more efficient. The magnitude of the associated catalytic current in both cases depends on the number of immersion and withdrawal steps. Interestingly, mediatorless catalysis at electrodes obtained from oppositely charged particles is more efficient than mediated catalysis.

Efficient RNA structure comparison algorithms.

Science.gov (United States)

Arslan, Abdullah N; Anandan, Jithendar; Fry, Eric; Monschke, Keith; Ganneboina, Nitin; Bowerman, Jason

2017-12-01

Recently proposed relative addressing-based ([Formula: see text]) RNA secondary structure representation has important features by which an RNA structure database can be stored into a suffix array. A fast substructure search algorithm has been proposed based on binary search on this suffix array. Using this substructure search algorithm, we present a fast algorithm that finds the largest common substructure of given multiple RNA structures in [Formula: see text] format. The multiple RNA structure comparison problem is NP-hard in its general formulation. We introduced a new problem for comparing multiple RNA structures. This problem has more strict similarity definition and objective, and we propose an algorithm that solves this problem efficiently. We also develop another comparison algorithm that iteratively calls this algorithm to locate nonoverlapping large common substructures in compared RNAs. With the new resulting tools, we improved the RNASSAC website (linked from http://faculty.tamuc.edu/aarslan ). This website now also includes two drawing tools: one specialized for preparing RNA substructures that can be used as input by the search tool, and another one for automatically drawing the entire RNA structure from a given structure sequence.

Jet substructure using semi-inclusive jet functions in SCET

Energy Technology Data Exchange (ETDEWEB)

Kang, Zhong-Bo [Theoretical Division, Los Alamos National Laboratory,Los Alamos, NM 87545 (United States); Department of Physics and Astronomy, University of California,Los Angeles, CA 90095 (United States); Ringer, Felix; Vitev, Ivan [Theoretical Division, Los Alamos National Laboratory,Los Alamos, NM 87545 (United States)

2016-11-25

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{sub i}{sup h}(z=ω{sub J}/ω,z{sub h}=ω{sub h}/ω{sub J},ω{sub 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{sub J}), and the hadron h (ω{sub 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{sub i}{sup h}(z,z{sub h},ω{sub 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{sub R}) accuracy. In combination with the fixed NLO calculation, we obtain NLO+NLL{sub 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.

Nucleosome–nucleosome interactions via histone tails and linker DNA regulate nuclear rigidity

Science.gov (United States)

Shimamoto, Yuta; Tamura, Sachiko; Masumoto, Hiroshi; Maeshima, Kazuhiro

2017-01-01

Cells, as well as the nuclei inside them, experience significant mechanical stress in diverse biological processes, including contraction, migration, and adhesion. The structural stability of nuclei must therefore be maintained in order to protect genome integrity. Despite extensive knowledge on nuclear architecture and components, however, the underlying physical and molecular mechanisms remain largely unknown. We address this by subjecting isolated human cell nuclei to microneedle-based quantitative micromanipulation with a series of biochemical perturbations of the chromatin. We find that the mechanical rigidity of nuclei depends on the continuity of the nucleosomal fiber and interactions between nucleosomes. Disrupting these chromatin features by varying cation concentration, acetylating histone tails, or digesting linker DNA results in loss of nuclear rigidity. In contrast, the levels of key chromatin assembly factors, including cohesin, condensin II, and CTCF, and a major nuclear envelope protein, lamin, are unaffected. Together with in situ evidence using living cells and a simple mechanical model, our findings reveal a chromatin-based regulation of the nuclear mechanical response and provide insight into the significance of local and global chromatin structures, such as those associated with interdigitated or melted nucleosomal fibers. PMID:28428255

Role of H1 linker histones in mammalian development and stem cell differentiation.

Science.gov (United States)

Pan, Chenyi; Fan, Yuhong

2016-03-01

H1 linker histones are key chromatin architectural proteins facilitating the formation of higher order chromatin structures. The H1 family constitutes the most heterogeneous group of histone proteins, with eleven non-allelic H1 variants in mammals. H1 variants differ in their biochemical properties and exhibit significant sequence divergence from one another, yet most of them are highly conserved during evolution from mouse to human. H1 variants are differentially regulated during development and their cellular compositions undergo dramatic changes in embryogenesis, gametogenesis, tissue maturation and cellular differentiation. As a group, H1 histones are essential for mouse development and proper stem cell differentiation. Here we summarize our current knowledge on the expression and functions of H1 variants in mammalian development and stem cell differentiation. Their diversity, sequence conservation, complex expression and distinct functions suggest that H1s mediate chromatin reprogramming and contribute to the large variations and complexity of chromatin structure and gene expression in the mammalian genome. Copyright © 2015 Elsevier B.V. All rights reserved.

Highly Tissue Substructure-Specific Effects of Human Papilloma Virus in Mucosa of HIV-Infected Patients Revealed by Laser-Dissection Microscopy-Assisted Gene Expression Profiling

Science.gov (United States)

Baumgarth, Nicole; Szubin, Richard; Dolganov, Greg M.; Watnik, Mitchell R.; Greenspan, Deborah; Da Costa, Maria; Palefsky, Joel M.; Jordan, Richard; Roederer, Mario; Greenspan, John S.

2004-01-01

Human papilloma virus (HPV) causes focal infections of epithelial layers in skin and mucosa. HIV-infected patients on highly active antiretroviral therapy (HAART) appear to be at increased risk of developing HPV-induced oral warts. To identify the mechanisms that allow long-term infection of oral epithelial cells in these patients, we used a combination of laser-dissection microscopy (LDM) and highly sensitive and quantitative, non-biased, two-step multiplex real-time RT-PCR to study pathogen-induced alterations of specific tissue subcompartments. Expression of 166 genes was compared in three distinct epithelial and subepithelial compartments isolated from biopsies of normal mucosa from HIV-infected and non-infected patients and of HPV32-induced oral warts from HIV-infected patients. In contrast to the underlying HIV infection and/or HAART, which did not significantly elaborate tissue substructure-specific effects, changes in oral warts were strongly tissue substructure-specific. HPV 32 seems to establish infection by selectively enhancing epithelial cell growth and differentiation in the stratum spinosum and to evade the immune system by actively suppressing inflammatory responses in adjacent underlying tissues. With this highly sensitive and quantitative method tissue-specific expression of hundreds of genes can be studied simultaneously in a few cells. Because of its large dynamic measurement range it could also become a method of choice to confirm and better quantify results obtained by microarray analysis. PMID:15331396

Quercetin-glutamic acid conjugate with a non-hydrolysable linker; a novel scaffold for multidrug resistance reversal agents through inhibition of P-glycoprotein.

Science.gov (United States)

Kim, Mi Kyoung; Kim, Yunyoung; Choo, Hyunah; Chong, Youhoon

2017-02-01

Previously, we have reported remarkable effect of a quercetin-glutamic acid conjugate to reverse multidrug resistance (MDR) of cancer cells to a broad spectrum of anticancer agents through inhibition of P-glycoprotein (Pgp)-mediated drug efflux. Due to the hydrolysable nature, MDR-reversal activity of the quercetin conjugate was attributed to its hydrolysis product, quercetin. However, several lines of evidence demonstrated that the intact quercetin-glutamic acid conjugate has stronger MDR-reversal activity than quercetin. In order to evaluate this hypothesis and to identify a novel scaffold for MDR-reversal agents, we prepared quercetin conjugates with a glutamic acid attached at the 7-O position via a non-hydrolysable linker. Pgp inhibition assay, Pgp ATPase assay, and MDR-reversal activity assay were performed, and the non-hydrolysable quercetin conjugates showed significantly higher activities compared with those of quercetin. Unfortunately, the quercetin conjugates were not as effective as verapamil in Pgp-inhibition and thereby reversing MDR, but it is worth to note that the structurally modified quercetin conjugates with a non-cleavable linker showed significantly improved MDR-reversal activity compared with quercetin. Taken together, the quercetin conjugates with appropriate structural modifications were shown to have a potential to serve as a scaffold for the design of novel MDR-reversal agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Site specific replacements of a single loop nucleoside with a dibenzyl linker may switch the activity of TBA from anticoagulant to antiproliferative.

Science.gov (United States)

Scuotto, Maria; Rivieccio, Elisa; Varone, Alessia; Corda, Daniela; Bucci, Mariarosaria; Vellecco, Valentina; Cirino, Giuseppe; Virgilio, Antonella; Esposito, Veronica; Galeone, Aldo; Borbone, Nicola; Varra, Michela; Mayol, Luciano

2015-09-18

Many antiproliferative G-quadruplexes (G4s) arise from the folding of GT-rich strands. Among these, the Thrombin Binding Aptamer (TBA), as a rare example, adopts a monomolecular well-defined G4 structure. Nevertheless, the potential anticancer properties of TBA are severely hampered by its anticoagulant action and, consequently, no related studies have appeared so far in the literature. We wish to report here that suitable chemical modifications in the TBA sequence can preserve its antiproliferative over anticoagulant activity. Particularly, we replaced one residue of the TT or TGT loops with a dibenzyl linker to develop seven new quadruplex-forming TBA based sequences (TBA-bs), which were studied for their structural (CD, CD melting, 1D NMR) and biological (fibrinogen, PT and MTT assays) properties. The three-dimensional structures of the TBA-bs modified at T13 (TBA-bs13) or T12 (TBA-bs12), the former endowed with selective antiproliferative activity, and the latter acting as potently as TBA in both coagulation and MTT assays, were further studied by 2D NMR restrained molecular mechanics. The comparative structural analyses indicated that neither the stability, nor the topology of the G4s, but the different localization of the two benzene rings of the linker was responsible for the loss of the antithrombin activity for TBA-bs13. © Crown copyright 2015.

Mutations in B3GALT6, which encodes a glycosaminoglycan linker region enzyme, cause a spectrum of skeletal and connective tissue disorders.

Science.gov (United States)

Nakajima, Masahiro; Mizumoto, Shuji; Miyake, Noriko; Kogawa, Ryo; Iida, Aritoshi; Ito, Hironori; Kitoh, Hiroshi; Hirayama, Aya; Mitsubuchi, Hiroshi; Miyazaki, Osamu; Kosaki, Rika; Horikawa, Reiko; Lai, Angeline; Mendoza-Londono, Roberto; Dupuis, Lucie; Chitayat, David; Howard, Andrew; Leal, Gabriela F; Cavalcanti, Denise; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Watanabe, Shigehiko; Lausch, Ekkehart; Unger, Sheila; Bonafé, Luisa; Ohashi, Hirofumi; Superti-Furga, Andrea; Matsumoto, Naomichi; Sugahara, Kazuyuki; Nishimura, Gen; Ikegawa, Shiro

2013-06-06

Proteoglycans (PGs) are a major component of the extracellular matrix in many tissues and function as structural and regulatory molecules. PGs are composed of core proteins and glycosaminoglycan (GAG) side chains. The biosynthesis of GAGs starts with the linker region that consists of four sugar residues and is followed by repeating disaccharide units. By exome sequencing, we found that B3GALT6 encoding an enzyme involved in the biosynthesis of the GAG linker region is responsible for a severe skeletal dysplasia, spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMD-JL1). B3GALT6 loss-of-function mutations were found in individuals with SEMD-JL1 from seven families. In a subsequent candidate gene study based on the phenotypic similarity, we found that B3GALT6 is also responsible for a connective tissue disease, Ehlers-Danlos syndrome (progeroid form). Recessive loss-of-function mutations in B3GALT6 result in a spectrum of disorders affecting a broad range of skeletal and connective tissues characterized by lax skin, muscle hypotonia, joint dislocation, and spinal deformity. The pleiotropic phenotypes of the disorders indicate that B3GALT6 plays a critical role in a wide range of biological processes in various tissues, including skin, bone, cartilage, tendon, and ligament. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

A histidine-rich linker region in peptidylglycine α-amidating monooxygenase has the properties of a pH sensor.

Science.gov (United States)

Vishwanatha, Kurutihalli; Bäck, Nils; Mains, Richard E; Eipper, Betty A

2014-05-02

Decreasing luminal pH is thought to play a role in the entry of newly synthesized and endocytosed membrane proteins into secretory granules. The two catalytic domains of peptidylglycine α-amidating monooxygenase (PAM), a type I integral membrane protein, catalyze the sequential reactions that convert peptidyl-Gly substrates into amidated products. We explored the hypothesis that a conserved His-rich cluster (His-Gly-His-His) in the linker region connecting its two catalytic domains senses pH and affects PAM trafficking by mutating these His residues to Ala (Ala-Gly-Ala-Ala; H3A). Purified recombinant wild-type and H3A linker peptides were examined using circular dichroism and tryptophan fluorescence; mutation of the His cluster largely eliminated its pH sensitivity. An enzymatically active PAM protein with the same mutations (PAM-1/H3A) was expressed in HEK293 cells and AtT-20 corticotrope tumor cells. Metabolic labeling followed by immunoprecipitation revealed more rapid loss of newly synthesized PAM-1/H3A than PAM-1; although release of newly synthesized monofunctional PHM/H3A was increased, release of soluble bifunctional PAM/H3A, a product of the endocytic pathway, was decreased. Surface biotinylation revealed rapid loss of PAM-1/H3A, with no detectable return of the mutant protein to secretory granules. Consistent with its altered endocytic trafficking, little PAM-1/H3A was subjected to regulated intramembrane proteolysis followed by release of a small nuclear-targeted cytosolic fragment. AtT-20 cells expressing PAM-1/H3A adopted the morphology of wild-type AtT-20 cells; secretory products no longer accumulated in the trans-Golgi network and secretory granule exocytosis was more responsive to secretagogue.

Boosting the charged Higgs search prospects using jet substructure at the LHC

Energy Technology Data Exchange (ETDEWEB)

Li, Jinmian [Center of Excellence for Particle Physics at Terascale, University of Adelaide,Adelaide, 5005 South (Australia); School of Physics, Korea Institute for Advanced Study,Seoul, 130-722 (Korea, Republic of); Patrick, Riley; Sharma, Pankaj; Williams, Anthony G. [Center of Excellence for Particle Physics at Terascale, University of Adelaide,Adelaide, 5005 South (Australia)

2016-11-28

Charged Higgs bosons are predicted in variety of theoretically well-motivated new physics models with extended Higgs sectors. In this study, we focus on a type-II two Higgs doublet model (2HDM-II) and consider a heavy charged Higgs with its mass ranging from 500 GeV to 1 TeV as dictated by the b→sγ constraints which render M{sub H{sup ±}}>480 GeV. We study the dominant production mode H{sup ±}t associated production with H{sup ±}→W{sup ±}A being the dominant decay channel when the pseudoscalar A is considerably lighter. For such a heavy charged Higgs, both the decay products W{sup ±} and A are relatively boosted. In such a scenario, we apply the jet substructure analysis of tagging the fat pseudoscalar and W jets in order to eliminate the standard model background efficiently. We perform a detailed detector simulation for the signal and background processes at the 14 TeV LHC. We introduce various kinematical cuts to determine the signal significance for a number of benchmark points with charged Higgs boson mass from 500 GeV to 1 TeV in the W{sup ±}A decay channel. Finally we perform a multivariate analysis utilizing a boosted decision tree algorithm to optimize these significances.

Analysis of Polymorphisms in the Merozoite Surface Protein-3a Gene and Two Microsatellite Loci in Sri Lankan Plasmodium vivax: Evidence of Population Substructure in Sri Lanka

DEFF Research Database (Denmark)

Schousboe, Mette L; Rajakaruna, Rupika S; Amerasinghe, Priyanie H

2011-01-01

Abstract. The geographical distribution of genetic variation in Plasmodium vivax samples (N = 386) from nine districts across Sri Lanka is described using three markers; the P. vivax merozoite surface protein-3a (Pvmsp-3a) gene, and the two microsatellites m1501 and m3502. At Pvmsp-3a, 11 alleles....... The results show evidence of high genetic diversity and possible population substructure of P. vivax populations in Sri Lanka....