Nucleotide-dependent switch in proteasome assembly mediated by the Nas6 chaperone

PubMed Central

Li, Frances; Tian, Geng; Langager, Deanna; Sokolova, Vladyslava; Finley, Daniel; Park, Soyeon

2017-01-01

The proteasome is assembled via the nine-subunit lid, nine-subunit base, and 28-subunit core particle (CP). Previous work has shown that the chaperones Rpn14, Nas6, Hsm3, and Nas2 each bind a specific ATPase subunit of the base and antagonize base–CP interaction. Here, we show that the Nas6 chaperone also obstructs base–lid association. Nas6 alternates between these two inhibitory modes according to the nucleotide state of the base. When ATP cannot be hydrolyzed, Nas6 interferes with base–lid, but not base–CP, association. In contrast, under conditions of ATP hydrolysis, Nas6 obstructs base–CP, but not base–lid, association. Modeling of Nas6 into cryoelectron microscopy structures of the proteasome suggests that Nas6 controls both base–lid affinity and base–CP affinity through steric hindrance; Nas6 clashes with the lid in the ATP-hydrolysis–blocked proteasome, but clashes instead with the CP in the ATP-hydrolysis–competent proteasome. Thus, Nas6 provides a dual mechanism to control assembly at both major interfaces of the proteasome. PMID:28137839

The impact of culture clash on deployed troops.

PubMed

Greene, Talya; Buckman, Joshua; Dandeker, Christopher; Greenberg, Neil

2010-12-01

Culture plays a crucial role in the military, helping the armed forces achieve their goals. However, cultural issues can negatively affect personnel's well-being and effectiveness, especially when there is a "clash" between military and other cultures. The literature suggests there should be more training and education on individual service cultures, as well as other countries' military cultures to improve cooperation and coordination during joint operations and working in multinational forces. A greater knowledge of local cultures may help avoid offending noncombatants. When deployment ends, service personnel need more support when they transition back to civilian culture.

Crystallographic characterization of the ribosomal binding site and molecular mechanism of action of Hygromycin A

PubMed Central

Kaminishi, Tatsuya; Schedlbauer, Andreas; Fabbretti, Attilio; Brandi, Letizia; Ochoa-Lizarralde, Borja; He, Cheng-Guang; Milón, Pohl; Connell, Sean R.; Gualerzi, Claudio O.; Fucini, Paola

2015-01-01

Hygromycin A (HygA) binds to the large ribosomal subunit and inhibits its peptidyl transferase (PT) activity. The presented structural and biochemical data indicate that HygA does not interfere with the initial binding of aminoacyl-tRNA to the A site, but prevents its subsequent adjustment such that it fails to act as a substrate in the PT reaction. Structurally we demonstrate that HygA binds within the peptidyl transferase center (PTC) and induces a unique conformation. Specifically in its ribosomal binding site HygA would overlap and clash with aminoacyl-A76 ribose moiety and, therefore, its primary mode of action involves sterically restricting access of the incoming aminoacyl-tRNA to the PTC. PMID:26464437

Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Žáková, Lenka; Kletvíková, Emília; Lepšík, Martin

[AsnB26]- and [GlyB26]-insulin mutants attain a B26-turn like fold without assistance of chemical modifications. Their structures match the insulin receptor interface and expand the spectrum of insulin conformations. The structural characterization of the insulin–insulin receptor (IR) interaction still lacks the conformation of the crucial B21–B30 insulin region, which must be different from that in its storage forms to ensure effective receptor binding. Here, it is shown that insulin analogues modified by natural amino acids at the TyrB26 site can represent an active form of this hormone. In particular, [AsnB26]-insulin and [GlyB26]-insulin attain a B26-turn-like conformation that differs from that inmore » all known structures of the native hormone. It also matches the receptor interface, avoiding substantial steric clashes. This indicates that insulin may attain a B26-turn-like conformation upon IR binding. Moreover, there is an unexpected, but significant, binding specificity of the AsnB26 mutant for predominantly the metabolic B isoform of the receptor. As it is correlated with the B26 bend of the B-chain of the hormone, the structures of AsnB26 analogues may provide the first structural insight into the structural origins of differential insulin signalling through insulin receptor A and B isoforms.« less

Fast exploration of an optimal path on the multidimensional free energy surface

PubMed Central

Chen, Changjun

2017-01-01

In a reaction, determination of an optimal path with a high reaction rate (or a low free energy barrier) is important for the study of the reaction mechanism. This is a complicated problem that involves lots of degrees of freedom. For simple models, one can build an initial path in the collective variable space by the interpolation method first and then update the whole path constantly in the optimization. However, such interpolation method could be risky in the high dimensional space for large molecules. On the path, steric clashes between neighboring atoms could cause extremely high energy barriers and thus fail the optimization. Moreover, performing simulations for all the snapshots on the path is also time-consuming. In this paper, we build and optimize the path by a growing method on the free energy surface. The method grows a path from the reactant and extends its length in the collective variable space step by step. The growing direction is determined by both the free energy gradient at the end of the path and the direction vector pointing at the product. With fewer snapshots on the path, this strategy can let the path avoid the high energy states in the growing process and save the precious simulation time at each iteration step. Applications show that the presented method is efficient enough to produce optimal paths on either the two-dimensional or the twelve-dimensional free energy surfaces of different small molecules. PMID:28542475

Dicyanovinylnaphthalenes for neuroimaging of amyloids and relationships of electronic structures and geometries to binding affinities

PubMed Central

Petrič, Andrej; Johnson, Scott A.; Pham, Hung V.; Li, Ying; Čeh, Simon; Golobič, Amalija; Agdeppa, Eric D.; Timbol, Gerald; Liu, Jie; Keum, Gyochang; Satyamurthy, Nagichettiar; Kepe, Vladimir; Houk, Kendall N.; Barrio, Jorge R.

2012-01-01

The positron-emission tomography (PET) probe 2-(1-[6-[(2-fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene) (FDDNP) is used for the noninvasive brain imaging of amyloid-β (Aβ) and other amyloid aggregates present in Alzheimer’s disease and other neurodegenerative diseases. A series of FDDNP analogs has been synthesized and characterized using spectroscopic and computational methods. The binding affinities of these molecules have been measured experimentally and explained through the use of a computational model. The analogs were created by systematically modifying the donor and the acceptor sides of FDDNP to learn the structural requirements for optimal binding to Aβ aggregates. FDDNP and its analogs are neutral, environmentally sensitive, fluorescent molecules with high dipole moments, as evidenced by their spectroscopic properties and dipole moment calculations. The preferred solution-state conformation of these compounds is directly related to the binding affinities. The extreme cases were a nonplanar analog t-butyl-FDDNP, which shows low binding affinity for Aβ aggregates (520 nM Ki) in vitro and a nearly planar tricyclic analog cDDNP, which displayed the highest binding affinity (10 pM Ki). Using a previously published X-ray crystallographic model of 1,1-dicyano-2-[6-(dimethylamino)naphthalen-2-yl]propene (DDNP) bound to an amyloidogenic Aβ peptide model, we show that the binding affinity is inversely related to the distortion energy necessary to avoid steric clashes along the internal surface of the binding channel. PMID:23012452

RCrane: semi-automated RNA model building.

PubMed

Keating, Kevin S; Pyle, Anna Marie

2012-08-01

RNA crystals typically diffract to much lower resolutions than protein crystals. This low-resolution diffraction results in unclear density maps, which cause considerable difficulties during the model-building process. These difficulties are exacerbated by the lack of computational tools for RNA modeling. Here, RCrane, a tool for the partially automated building of RNA into electron-density maps of low or intermediate resolution, is presented. This tool works within Coot, a common program for macromolecular model building. RCrane helps crystallographers to place phosphates and bases into electron density and then automatically predicts and builds the detailed all-atom structure of the traced nucleotides. RCrane then allows the crystallographer to review the newly built structure and select alternative backbone conformations where desired. This tool can also be used to automatically correct the backbone structure of previously built nucleotides. These automated corrections can fix incorrect sugar puckers, steric clashes and other structural problems.

Structural impact of complete CpG methylation within target DNA on specific complex formation of the inducible transcription factor Egr-1.

PubMed

Zandarashvili, Levani; White, Mark A; Esadze, Alexandre; Iwahara, Junji

2015-07-08

The inducible transcription factor Egr-1 binds specifically to 9-bp target sequences containing two CpG sites that can potentially be methylated at four cytosine bases. Although it appears that complete CpG methylation would make an unfavorable steric clash in the previous crystal structures of the complexes with unmethylated or partially methylated DNA, our affinity data suggest that DNA recognition by Egr-1 is insensitive to CpG methylation. We have determined, at a 1.4-Å resolution, the crystal structure of the Egr-1 zinc-finger complex with completely methylated target DNA. Structural comparison of the three different methylation states reveals why Egr-1 can recognize the target sequences regardless of CpG methylation. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Intermolecular ‘cross-torque’: the N4-cytosine propargyl residue is rotated to the ‘CH’-edge as a result of Watson–Crick interaction

PubMed Central

Domingo, Olwen; Hellmuth, Isabell; Jäschke, Andres; Kreutz, Christoph; Helm, Mark

2015-01-01

Propargyl groups are attractive functional groups for labeling purposes, as they allow CuAAC-mediated bioconjugation. Their size minimally exceeds that of a methyl group, the latter being frequent in natural nucleotide modifications. To understand under which circumstances propargyl-containing oligodeoxynucleotides preserve base pairing, we focused on the exocyclic amine of cytidine. Residues attached to the exocyclic N4 may orient away from or toward the Watson–Crick face, ensuing dramatic alteration of base pairing properties. ROESY-NMR experiments suggest a uniform orientation toward the Watson–Crick face of N4-propargyl residues in derivatives of both deoxycytidine and 5-methyl-deoxycytidine. In oligodeoxynucleotides, however, UV-melting indicated that N4-propargyl-deoxycytidine undergoes standard base pairing. This implies a rotation of the propargyl moiety toward the ‘CH’-edge as a result of base pairing on the Watson–Crick face. In oligonucleotides containing the corresponding 5-methyl-deoxycytidine derivative, dramatically reduced melting temperatures indicate impaired Watson–Crick base pairing. This was attributed to a steric clash of the propargyl moiety with the 5-methyl group, which prevents back rotation to the ‘CH’-edge, consequently preventing Watson–Crick geometry. Our results emphasize the tendency of an opposing nucleic acid strand to mechanically rotate single N4-substituents to make way for Watson–Crick base pairing, providing no steric hindrance is present on the ‘CH’-edge. PMID:25934805

Diverse structural approaches to haem appropriation by pathogenic bacteria.

PubMed

Hare, Stephen A

2017-04-01

The critical need for iron presents a challenge for pathogenic bacteria that must survive in an environment bereft of accessible iron due to a natural low bioavailability and their host's nutritional immunity. Appropriating haem, either direct from host haemoproteins or by secreting haem-scavenging haemophores, is one way pathogenic bacteria can overcome this challenge. After capturing their target, haem appropriation systems must remove haem from a high-affinity binding site (on the host haemoprotein or bacterial haemophore) and transfer it to a binding site of lower affinity on a bacterial receptor. Structural information is now available to show how, using a combination of induced structural changes and steric clashes, bacteria are able to extract haem from haemophores, haemopexin and haemoglobin. This review focuses on structural descriptions of these bacterial haem acquisition systems, summarising how they bind haem and their target haemoproteins with particularly emphasis on the mechanism of haem extraction. Copyright © 2017 The Author. Published by Elsevier B.V. All rights reserved.

Protocols for Molecular Dynamics Simulations of RNA Nanostructures.

PubMed

Kim, Taejin; Kasprzak, Wojciech K; Shapiro, Bruce A

2017-01-01

Molecular dynamics (MD) simulations have been used as one of the main research tools to study a wide range of biological systems and bridge the gap between X-ray crystallography or NMR structures and biological mechanism. In the field of RNA nanostructures, MD simulations have been used to fix steric clashes in computationally designed RNA nanostructures, characterize the dynamics, and investigate the interaction between RNA and other biomolecules such as delivery agents and membranes.In this chapter we present examples of computational protocols for molecular dynamics simulations in explicit and implicit solvent using the Amber Molecular Dynamics Package. We also show examples of post-simulation analysis steps and briefly mention selected tools beyond the Amber package. Limitations of the methods, tools, and protocols are also discussed. Most of the examples are illustrated for a small RNA duplex (helix), but the protocols are applicable to any nucleic acid structure, subject only to the computational speed and memory limitations of the hardware available to the user.

Structure of a bacterial RNA polymerase holoenzyme open promoter complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bae, Brian; Feklistov, Andrey; Lass-Napiorkowska, Agnieszka

2015-09-08

Initiation of transcription is a primary means for controlling gene expression. In bacteria, the RNA polymerase (RNAP) holoenzyme binds and unwinds promoter DNA, forming the transcription bubble of the open promoter complex (RPo). We have determined crystal structures, refined to 4.14 Å-resolution, of RPo containing Thermus aquaticus RNAP holoenzyme and promoter DNA that includes the full transcription bubble. The structures, combined with biochemical analyses, reveal key features supporting the formation and maintenance of the double-strand/single-strand DNA junction at the upstream edge of the -10 element where bubble formation initiates. The results also reveal RNAP interactions with duplex DNA just upstreammore » of the -10 element and potential protein/DNA interactions that direct the DNA template strand into the RNAP active site. Addition of an RNA primer to yield a 4 base-pair post-translocated RNA:DNA hybrid mimics an initially transcribing complex at the point where steric clash initiates abortive initiation and σA dissociation.« less

Structure of a bacterial RNA polymerase holoenzyme open promoter complex

DOE PAGES

Bae, Brian; Feklistov, Andrey; Lass-Napiorkowska, Agnieszka; ...

2015-09-08

Initiation of transcription is a primary means for controlling gene expression. In bacteria, the RNA polymerase (RNAP) holoenzyme binds and unwinds promoter DNA, forming the transcription bubble of the open promoter complex (RPo). We have determined crystal structures, refined to 4.14 Å-resolution, of RPo containing Thermus aquaticus RNAP holoenzyme and promoter DNA that includes the full transcription bubble. The structures, combined with biochemical analyses, reveal key features supporting the formation and maintenance of the double-strand/single-strand DNA junction at the upstream edge of the -10 element where bubble formation initiates. The results also reveal RNAP interactions with duplex DNA just upstreammore » of the -10 element and potential protein/DNA interactions that direct the DNA template strand into the RNAP active site. Additionally a RNA primer to yield a 4 base-pair post-translocated RNA:DNA hybrid mimics an initially transcribing complex at the point where steric clash initiates abortive initiation and σ A dissociation.« less

All-Atom Simulations Reveal How Single-Point Mutations Promote Serpin Misfolding

NASA Astrophysics Data System (ADS)

Wang, Fang; Orioli, Simone; Ianeselli, Alan; Spagnolli, Giovanni; a Beccara, Silvio; Gershenson, Anne; Faccioli, Pietro; Wintrode, Patrick L.

2018-05-01

Protein misfolding is implicated in many diseases, including the serpinopathies. For the canonical inhibitory serpin {\\alpha}1-antitrypsin (A1AT), mutations can result in protein deficiencies leading to lung disease, and misfolded mutants can accumulate in hepatocytes leading to liver disease. Using all-atom simulations based on the recently developed Bias Functional algorithm we elucidate how wild-type A1AT folds and how the disease-associated S (Glu264Val) and Z (Glu342Lys) mutations lead to misfolding. The deleterious Z mutation disrupts folding at an early stage, while the relatively benign S mutant shows late stage minor misfolding. A number of suppressor mutations ameliorate the effects of the Z mutation and simulations on these mutants help to elucidate the relative roles of steric clashes and electrostatic interactions in Z misfolding. These results demonstrate a striking correlation between atomistic events and disease severity and shine light on the mechanisms driving chains away from their correct folding routes.

Structural insights into the intertwined dimer of fyn SH2.

PubMed

Huculeci, Radu; Garcia-Pino, Abel; Buts, Lieven; Lenaerts, Tom; van Nuland, Nico

2015-12-01

Src homology 2 domains are interaction modules dedicated to the recognition of phosphotyrosine sites incorporated in numerous proteins found in intracellular signaling pathways. Here we provide for the first time structural insight into the dimerization of Fyn SH2 both in solution and in crystalline conditions, providing novel crystal structures of both the dimer and peptide-bound structures of Fyn SH2. Using nuclear magnetic resonance chemical shift analysis, we show how the peptide is able to eradicate the dimerization, leading to monomeric SH2 in its bound state. Furthermore, we show that Fyn SH2's dimer form differs from other SH2 dimers reported earlier. Interestingly, the Fyn dimer can be used to construct a completed dimer model of Fyn without any steric clashes. Together these results extend our understanding of SH2 dimerization, giving structural details, on one hand, and suggesting a possible physiological relevance of such behavior, on the other hand. © 2015 The Protein Society.

Al Qaeda and U.S. Policy: Middle East and Africa

DTIC Science & Technology

2016-08-11

states that, “the tensions between AQ and ISIL escalated in a number of regions during 2015 and likely resulted in increased violence in several parts...the two groups clashed frequently, leading Zawahiri to issue appeals for unity and a halt to intra-jihadist violence . On February 3, 2014, Zawahiri...avoid targeting their enemies in public spaces such as mosques and markets , where an attack could harm other Muslims or noncombatants. In September

Steric sea level change in the Bay of Bengal: investigating the most variable component of sea level change

NASA Astrophysics Data System (ADS)

Uebbing, Bernd; Kusche, Jürgen; Rietbroek, Roelof; Shum, Ck

2015-04-01

Regional sea level change is influenced by contributions from mass sources, like melting of glaciers and the ice-sheets in Greenland and Antarctica, as well as steric contributions from changes in temperature and salinity of the oceans. Radar altimetry indicates a sea level trend in the Bay of Bengal of about 6 mm- yr over the time period of 2002-2014, which is significantly larger than the global mean trend. Here, we explain 80% of this rise by steric contributions and 20% by mass-related contributions. The increased rise of sea level in the Bay of Bengal threatens the coastal vulnerability of the surrounding countries like Bangladesh, where this effect is exacerbated in combination with land subsidence of the very low lying coastal areas. The BanD-AID (Bangladesh Delta: Assessment of the Causes of Sea-level Rise Hazards and Integrated Development of Predictive Modeling Towards Mitigation and Adaptation) project tries to assess the current and future sea level rise and its impacts on the people living in the threatened coastal areas. As a part of this, it is necessary to analyze the different mass and steric contributors to the total sea level rise to aid in the prediction of future risks. We use data from radar altimetry and the GRACE mission to separate the total sea level rise into contributions from mass sources and steric changes. In our approach, temporal GRACE gravity data and Jason-1 and -2 along track altimetry data are fitted to time invariant spatial patterns (fingerprints) to avoid problems with GRACE resolution, filtering, geocenter and related issues. Our results show that in the Bay of Bengal the steric component is influenced by annual and interannual phenomena and, at the same time, it is significantly larger compared to the individual mass contributions, which show a linear and relatively stable behavior over time. We validate the steric component of our inversion by comparing it to independent steric estimates from 4-D gridded temperature and salinity products from different ARGO processing facilities. We also compare to the classical approach of subtracting the mass component, estimated by GRACE, from the total sea level change, measured by altimetry. Furthermore, we assess the sensitivity of our inversion to the normalized steric fingerprints, which are either based on ARGO fields or derived from ocean modeling. While most steric changes are taking place in the upper 700 m of the ocean, our inversion also allows us to (indirectly) assess the influence from the deep ocean, which is not negligible for the total steric trend.

VizieR Online Data Catalog: Properties of giant arcs behind CLASH clusters (Xu+, 2016)

NASA Astrophysics Data System (ADS)

Xu, B.; Postman, M.; Meneghetti, M.; Seitz, S.; Zitrin, A.; Merten, J.; Maoz, D.; Frye, B.; Umetsu, K.; Zheng, W.; Bradley, L.; Vega, J.; Koekemoer, A.

2018-01-01

Giant arcs are found in the CLASH images and in simulated images that mimic the CLASH data, using an efficient automated arc-finding algorithm whose selection function has been carefully quantified. CLASH is a 524-orbit multicycle treasury program that targeted 25 massive clusters with 0.18=6.5 in 20 X-ray-selected CLASH clusters. After applying our minimum arc length criterion l>=6", the arc count drops to 81 giant arcs selected from the 20 X-ray-selected CLASH clusters. (2 data files).

Steric Effects of Solvent Molecules on SN2 Substitution Dynamics.

PubMed

Liu, Xu; Xie, Jing; Zhang, Jiaxu; Yang, Li; Hase, William L

2017-04-20

Influences of solvent molecules on S N 2 reaction dynamics of microsolvated F - (H 2 O) n with CH 3 I, for n = 0-3, are uncovered by direct chemical dynamics simulations. The direct substitution mechanism, which is important without microsolvation, is quenched dramatically upon increasing hydration. The water molecules tend to force reactive encounters to proceed through the prereaction collision complex leading to indirect reaction. In contrast to F - (H 2 O), reaction with higher hydrated ions shows a strong propensity for ion desolvation in the entrance channel, diminishing steric hindrance for nucleophilic attack. Thus, nucleophilic substitution avoids the potential energy barrier with all of the solvent molecules intact and instead occurs through the less solvated barrier, which is energetically unexpected because the former barrier has a lower energy. The work presented here reveals a trade-off between reaction energetics and steric effects, with the latter found to be crucial in understanding how hydration influences microsolvated S N 2 dynamics.

Structural Basis for Inactivation of the Human Pyruvate Dehydrogenase Complex by Phosphorylation: Role of Disordered Phosphorylation Loops

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kato, Masato; Wynn, R. Max; Chuang, Jacinta L.

2009-09-11

We report the crystal structures of the phosporylated pyruvate dehydrogenase (E1p) component of the human pyruvate dehydrogenase complex (PDC). The complete phosphorylation at Ser264-{alpha} (site 1) of a variant E1p protein was achieved using robust pyruvate dehydrogenase kinase 4 free of the PDC core. We show that unlike its unmodified counterpart, the presence of a phosphoryl group at Ser264-{alpha} prevents the cofactor thiamine diphosphate-induced ordering of the two loops carrying the three phosphorylation sites. The disordering of these phosphorylation loops is caused by a previously unrecognized steric clash between the phosphoryl group at site 1 and a nearby Ser266-{alpha}, whichmore » nullifies a hydrogen-bonding network essential for maintaining the loop conformations. The disordered phosphorylation loops impede the binding of lipoyl domains of the PDC core to E1p, negating the reductive acetylation step. This results in the disruption of the substrate channeling in the PDC, leading to the inactivation of this catalytic machine.« less

Design of N-acyl homoserine lactonase with high substrate specificity by a rational approach.

PubMed

Kyeong, Hyun-Ho; Kim, Jin-Hyun; Kim, Hak-Sung

2015-06-01

N-Acyl homoserine lactone (AHL) is a major quorum-sensing signaling molecule in many bacterial species. Quorum-quenching (QQ) enzymes, which degrade such signaling molecules, have attracted much attention as an approach to controlling and preventing bacterial virulence and pathogenesis. However, naturally occurring QQ enzymes show a broad substrate spectrum, raising the concern of unintentionally attenuating beneficial effects by symbiotic bacteria. Here we report the rational design of acyl homoserine lactonase with high substrate specificity. Through docking analysis, we identified three key residues which play a key role in the substrate preference of the enzyme. The key residues were changed in a way that increases hydrophobic contact with a substrate having a short acyl chain (C4-AHL) while generating steric clashes with that containing a long acyl chain (C12-AHL). The resulting mutants exhibited a significantly shifted preference toward a substrate with a short acyl chain. Molecular dynamics simulations suggested that the mutations affect the behavior of a flexible loop, allowing tighter binding of a substrate with a short acyl chain.

Structural Switch of Lysyl-tRNA Synthetase Between Translation and Transcription

PubMed Central

Ofir-Birin, Yifat; Fang, Pengfei; Bennett, Steven P.; Zhang, Hui-Min; Wang, Jing; Rachmin, Inbal; Shapiro, Ryan; Song, Jing; Dagan, Arie; Pozo, Jorge; Kim, Sunghoon; Marshall, Alan G.; Schimmel, Paul; Yang, Xiang-Lei; Nechushtan, Hovav; Razin, Ehud; Guo, Min

2013-01-01

SUMMARY Lysyl-tRNA synthetase (LysRS), a component of the translation apparatus, is released from the cytoplasmic multi-tRNA synthetase complex (MSC) to activate the transcription factor MITF in stimulated mast cells through undefined mechanisms. Here we show that Ser207-phosphorylation provokes a new conformer of LysRS that inactivates its translational, but activates its transcriptional function. The crystal structure of an MSC sub-complex established that LysRS is held in the MSC by binding to the N-terminus of the scaffold protein p38/AIMP2. Phosphorylation-created steric clashes at the LysRS domain interface disrupt its binding grooves for p38/AIMP2, releasing LysRS and provoking its nuclear translocation. This alteration also exposes the C-terminal domain of LysRS to bind to MITF and triggers LysRS-directed production of the second messenger Ap4A that activates MITF. Thus our results establish that a single conformational change triggered by phosphorylation leads to multiple effects driving an exclusive switch of LysRS function from translation to transcription. PMID:23159739

Automated protein structure modeling in CASP9 by I-TASSER pipeline combined with QUARK-based ab initio folding and FG-MD-based structure refinement

PubMed Central

Xu, Dong; Zhang, Jian; Roy, Ambrish; Zhang, Yang

2011-01-01

I-TASSER is an automated pipeline for protein tertiary structure prediction using multiple threading alignments and iterative structure assembly simulations. In CASP9 experiments, two new algorithms, QUARK and FG-MD, were added to the I-TASSER pipeline for improving the structural modeling accuracy. QUARK is a de novo structure prediction algorithm used for structure modeling of proteins that lack detectable template structures. For distantly homologous targets, QUARK models are found useful as a reference structure for selecting good threading alignments and guiding the I-TASSER structure assembly simulations. FG-MD is an atomic-level structural refinement program that uses structural fragments collected from the PDB structures to guide molecular dynamics simulation and improve the local structure of predicted model, including hydrogen-bonding networks, torsion angles and steric clashes. Despite considerable progress in both the template-based and template-free structure modeling, significant improvements on protein target classification, domain parsing, model selection, and ab initio folding of beta-proteins are still needed to further improve the I-TASSER pipeline. PMID:22069036

Structural Refinement of Proteins by Restrained Molecular Dynamics Simulations with Non-interacting Molecular Fragments.

PubMed

Shen, Rong; Han, Wei; Fiorin, Giacomo; Islam, Shahidul M; Schulten, Klaus; Roux, Benoît

2015-10-01

The knowledge of multiple conformational states is a prerequisite to understand the function of membrane transport proteins. Unfortunately, the determination of detailed atomic structures for all these functionally important conformational states with conventional high-resolution approaches is often difficult and unsuccessful. In some cases, biophysical and biochemical approaches can provide important complementary structural information that can be exploited with the help of advanced computational methods to derive structural models of specific conformational states. In particular, functional and spectroscopic measurements in combination with site-directed mutations constitute one important source of information to obtain these mixed-resolution structural models. A very common problem with this strategy, however, is the difficulty to simultaneously integrate all the information from multiple independent experiments involving different mutations or chemical labels to derive a unique structural model consistent with the data. To resolve this issue, a novel restrained molecular dynamics structural refinement method is developed to simultaneously incorporate multiple experimentally determined constraints (e.g., engineered metal bridges or spin-labels), each treated as an individual molecular fragment with all atomic details. The internal structure of each of the molecular fragments is treated realistically, while there is no interaction between different molecular fragments to avoid unphysical steric clashes. The information from all the molecular fragments is exploited simultaneously to constrain the backbone to refine a three-dimensional model of the conformational state of the protein. The method is illustrated by refining the structure of the voltage-sensing domain (VSD) of the Kv1.2 potassium channel in the resting state and by exploring the distance histograms between spin-labels attached to T4 lysozyme. The resulting VSD structures are in good agreement with the consensus model of the resting state VSD and the spin-spin distance histograms from ESR/DEER experiments on T4 lysozyme are accurately reproduced.

Sustainable steric stabilization of colloidal titania nanoparticles

NASA Astrophysics Data System (ADS)

Elbasuney, Sherif

2017-07-01

A route to produce a stable colloidal suspension is essential if mono-dispersed particles are to be successfully synthesized, isolated, and used in subsequent nanocomposite manufacture. Dispersing nanoparticles in fluids was found to be an important approach for avoiding poor dispersion characteristics. However, there is still a great tendency for colloidal nanoparticles to flocculate over time. Steric stabilization can prevent coagulation by introducing a thick adsorbed organic layer which constitutes a significant steric barrier that can prevent the particle surfaces from coming into direct contact. One of the main features of hydrothermal synthesis technique is that it offers novel approaches for sustainable nanoparticle surface modification. This manuscript reports on the sustainable steric stabilization of titanium dioxide nanoparticles. Nanoparticle surface modification was performed via two main approaches including post-synthesis and in situ surface modification. The tuneable hydrothermal conditions (i.e. temperature, pressure, flow rates, and surfactant addition) were optimized to enable controlled steric stabilization in a continuous fashion. Effective post synthesis surface modification with organic ligand (dodecenyl succinic anhydride (DDSA)) was achieved; the optimum surface coating temperature was reported to be 180-240 °C to ensure DDSA ring opening and binding to titania nanoparticles. Organic-modified titania demonstrated complete change in surface properties from hydrophilic to hydrophobic and exhibited phase transfer from the aqueous phase to the organic phase. Exclusive surface modification in the reactor was found to be an effective approach; it demonstrated surfactant loading level 2.2 times that of post synthesis surface modification. Titania was also stabilized in aqueous media using poly acrylic acid (PAA) as polar polymeric dispersant. PAA-titania nanoparticles demonstrated a durable amorphous polymeric layer of 2 nm thickness. This manuscript revealed the state of the art for the real development of stable colloidal mono-dispersed particles with controlled surface properties.

Culture Clash Invades Miami: Oral Histories and Ethnography Center Stage

ERIC Educational Resources Information Center

Garcia, David G.

2008-01-01

Using a critical race theory (CRT) framework, this article compares the playwriting methods of the Chicano--Latino theater trio, Culture Clash, to a counterstorytelling methodology. The author uncovers the tenets of a critical race theater in the trio's site-specific ethnographic play, "Radio Mambo: Culture Clash Invades Miami". He…

Avoiding Steric Congestion in Dendrimer Growth through Proportionate Branching. A Twist on da Vinci's Rule of Tree Branching

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yue, Xuyi; Taraban, Marc B.; Hyland, Laura L.

2012-10-05

In making defect-free macromolecules, the challenge occurs during chemical synthesis. This challenge is especially pronounced in dendrimer synthesis where exponential growth quickly leads to steric congestion. To overcome this difficulty, proportionate branching in dendrimer growth is proposed. In proportionate branching, both the number and the length of branches increase exponentially but in opposite directions to mimic tree growth. The effectiveness of this strategy is demonstrated through the synthesis of a fluorocarbon dendron containing 243 chemically identical fluorine atoms with a MW of 9082 Da. Monodispersity is confirmed by nuclear magnetic resonance spectroscopy, mass spectrometry, and small-angle X-ray scattering. Moreover, growingmore » different parts proportionately, as nature does, could be a general strategy to achieve defect-free synthesis of macromolecules.« less

Transition State Gauche Effects Control the Torquoselectivities of the Electrocyclizations of Chiral 1-Azatrienes.

PubMed

Patel, Ashay; Vella, Joseph R; Ma, Zhi-Xiong; Hsung, R P; Houk, K N

2015-12-04

Hsung et al. have reported a series of torquoselective electrocyclizations of chiral 1-azahexa-1E,3Z,5E-trienes that yield functionalized dihydropyridines. To understand the origins of the torquoselectivities of these azaelectrocyclizations, we modeled these electrocyclic ring closures using the M06-2X density functional. A new stereochemical model that rationalizes the observed 1,2 stereoinduction emerges from these computations. This model is an improvement and generalization of the "inside-alkoxy" model used to rationalize stereoselectivities of the 1,3-dipolar cycloaddition of chiral allyl ethers and emphasizes a stabilizing hyperconjugative effect, which we have termed a transition state gauche effect. This stereoelectronic effect controls the conformational preferences at the electrocyclization transition states, and only in one of the allowed disrotatory electrocyclization transition states is the ideal stereoelectronic arrangement achieved without the introduction of a steric clash. Computational experiments confirm the role of this effect as a stereodeterminant since substrates with electropositive groups and electronegative groups have different conformational preferences at the transition state and undergo ring closure with divergent stereochemical outcomes. This predicted reversal of stereoselectivity for the ring closures of several silyl substituted azatrienes have been demonstrated experimentally.

Gaia: automated quality assessment of protein structure models.

PubMed

Kota, Pradeep; Ding, Feng; Ramachandran, Srinivas; Dokholyan, Nikolay V

2011-08-15

Increasing use of structural modeling for understanding structure-function relationships in proteins has led to the need to ensure that the protein models being used are of acceptable quality. Quality of a given protein structure can be assessed by comparing various intrinsic structural properties of the protein to those observed in high-resolution protein structures. In this study, we present tools to compare a given structure to high-resolution crystal structures. We assess packing by calculating the total void volume, the percentage of unsatisfied hydrogen bonds, the number of steric clashes and the scaling of the accessible surface area. We assess covalent geometry by determining bond lengths, angles, dihedrals and rotamers. The statistical parameters for the above measures, obtained from high-resolution crystal structures enable us to provide a quality-score that points to specific areas where a given protein structural model needs improvement. We provide these tools that appraise protein structures in the form of a web server Gaia (http://chiron.dokhlab.org). Gaia evaluates the packing and covalent geometry of a given protein structure and provides quantitative comparison of the given structure to high-resolution crystal structures. dokh@unc.edu Supplementary data are available at Bioinformatics online.

Computational Studies of Difference in Binding Modes of Peptide and Non-Peptide Inhibitors to MDM2/MDMX Based on Molecular Dynamics Simulations

PubMed Central

Chen, Jianzhong; Zhang, Dinglin; Zhang, Yuxin; Li, Guohui

2012-01-01

Inhibition of p53-MDM2/MDMX interaction is considered to be a promising strategy for anticancer drug design to activate wild-type p53 in tumors. We carry out molecular dynamics (MD) simulations to study the binding mechanisms of peptide and non-peptide inhibitors to MDM2/MDMX. The rank of binding free energies calculated by molecular mechanics generalized Born surface area (MM-GBSA) method agrees with one of the experimental values. The results suggest that van der Waals energy drives two kinds of inhibitors to MDM2/MDMX. We also find that the peptide inhibitors can produce more interaction contacts with MDM2/MDMX than the non-peptide inhibitors. Binding mode predictions based on the inhibitor-residue interactions show that the π–π, CH–π and CH–CH interactions dominated by shape complimentarity, govern the binding of the inhibitors in the hydrophobic cleft of MDM2/MDMX. Our studies confirm the residue Tyr99 in MDMX can generate a steric clash with the inhibitors due to energy and structure. This finding may theoretically provide help to develop potent dual-specific or MDMX inhibitors. PMID:22408446

Molecular basis for the catalytic inactivity of a naturally occurring near-null variant of human ALOX15.

PubMed

Horn, Thomas; Ivanov, Igor; Di Venere, Almerinda; Kakularam, Kumar Reddy; Reddanna, Pallu; Conrad, Melanie L; Richter, Constanze; Scheerer, Patrick; Kuhn, Hartmut

2013-12-01

Mammalian lipoxygenases belong to a family of lipid-peroxidizing enzymes, which have been implicated in cardiovascular, hyperproliferative and neurodegenerative diseases. Here we report that a naturally occurring mutation in the hALOX15 gene leads to expression of a catalytically near-null enzyme variant (hGly422Glu). The inactivity may be related to severe misfolding of the enzyme protein, which was concluded from CD-spectra as well as from thermal and chemical stability assays. In silico mutagenesis experiments suggest that most mutations at hGly422 have the potential to induce sterical clash, which might be considered a reason for protein misfolding. hGly422 is conserved among ALOX5, ALOX12 and ALOX15 isoforms and corresponding hALOX12 and hALOX5 mutants also exhibited a reduced catalytic activity. Interestingly, in the hALOX5 Gly429Glu mutants the reaction specificity of arachidonic acid oxygenation was shifted from 5S- to 8S- and 12R-H(p)ETE formation. Taken together, our data indicate that the conserved glycine is of functional importance for these enzyme variants and most mutants at this position lose catalytic activity. © 2013.

Modified Cross-Linking, Ligation, and Sequencing of Hybrids (qCLASH) Identifies Kaposi's Sarcoma-Associated Herpesvirus MicroRNA Targets in Endothelial Cells.

PubMed

Gay, Lauren A; Sethuraman, Sunantha; Thomas, Merin; Turner, Peter C; Renne, Rolf

2018-04-15

Kaposi's sarcoma (KS) tumors are derived from endothelial cells and express Kaposi's sarcoma-associated herpesvirus (KSHV) microRNAs (miRNAs). Although miRNA targets have been identified in B cell lymphoma-derived cells and epithelial cells, little has been done to characterize the KSHV miRNA targetome in endothelial cells. A recent innovation in the identification of miRNA targetomes, cross-linking, ligation, and sequencing of hybrids (CLASH), unambiguously identifies miRNAs and their targets by ligating the two species while both species are still bound within the RNA-induced silencing complex (RISC). We developed a streamlined quick CLASH (qCLASH) protocol that requires a lower cell input than the original method and therefore has the potential to be used on patient biopsy samples. Additionally, we developed a fast-growing, KSHV-negative endothelial cell line derived from telomerase-immortalized vein endothelial long-term culture (TIVE-LTC) cells. qCLASH was performed on uninfected cells and cells infected with either wild-type KSHV or a mutant virus lacking miR-K12-11/11*. More than 1,400 cellular targets of KSHV miRNAs were identified. Many of the targets identified by qCLASH lacked a canonical seed sequence match. Additionally, most target regions in mRNAs originated from the coding DNA sequence (CDS) rather than the 3' untranslated region (UTR). This set of genes includes some that were previously identified in B cells and some new genes that warrant further study. Pathway analysis of endothelial cell targets showed enrichment in cell cycle control, apoptosis, and glycolysis pathways, among others. Characterization of these new targets and the functional consequences of their repression will be important in furthering our understanding of the role of KSHV miRNAs in oncogenesis. IMPORTANCE KS lesions consist of endothelial cells latently infected with KSHV. Cells that make up these lesions express KSHV miRNAs. Identification of the targets of KSHV miRNAs will help us understand their role in viral oncogenesis. The cross-linking and sequencing of hybrids (CLASH) protocol is a method for unambiguously identifying miRNA targetomes. We developed a streamlined version of CLASH, called quick CLASH (qCLASH). qCLASH requires a lower initial input of cells than for its parent protocol. Additionally, a new fast-growing KSHV-negative endothelial cell line, named TIVE-EX-LTC cells, was established. qCLASH was performed on TIVE-EX-LTC cells latently infected with wild-type (WT) KSHV or a mutant virus lacking miR-K12-11/11*. A number of novel targets of KSHV miRNAs were identified, including targets of miR-K12-11, the ortholog of the cellular oncogenic miRNA (oncomiR) miR-155. Many of the miRNA targets were involved in processes related to oncogenesis, such as glycolysis, apoptosis, and cell cycle control. Copyright © 2018 American Society for Microbiology.

Structure of the lutein-binding domain of human StARD3 at 1.74 Å resolution and model of a complex with lutein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Horvath, Martin P., E-mail: martin.horvath@utah.edu; George, Evan W.; Tran, Quang T.

The structure of a START-domain protein known to bind lutein in the human retina is reported to an improved resolution limit. Rigid-body docking demonstrates that at least a portion of lutein must protrude from the large tunnel-like cavity characteristic of this helix-grip protein and suggests a mechanism for lutein binding specificity. A crystal structure of the lutein-binding domain of human StARD3 (StAR-related lipid-transfer protein 3; also known as MLN64) has been refined to 1.74 Å resolution. A previous structure of the same protein determined to 2.2 Å resolution highlighted homology with StARD1 and shared cholesterol-binding character. StARD3 has since beenmore » recognized as a carotenoid-binding protein in the primate retina, where its biochemical function of binding lutein with specificity appears to be well suited to recruit this photoprotective molecule. The current and previous structures correspond closely to each other (r.m.s.d. of 0.25 Å), especially in terms of the helix-grip fold constructed around a solvent-filled cavity. Regions of interest were defined with alternate conformations in the current higher-resolution structure, including Arg351 found within the cavity and Ω1, a loop of four residues found just outside the cavity entrance. Models of the complex with lutein generated by rigid-body docking indicate that one of the ionone rings must protrude outside the cavity, and this insight has implications for molecular interactions with transport proteins and enzymes that act on lutein. Interestingly, models with the ∊-ionone ring characteristic of lutein pointing towards the bottom of the cavity were associated with fewer steric clashes, suggesting that steric complementarity and ligand asymmetry may play a role in discriminating lutein from the other ocular carotenoids zeaxanthin and meso-zeaxanthin, which only have β-ionone rings.« less

Origins of structure in globular proteins.

PubMed Central

Chan, H S; Dill, K A

1990-01-01

The principal forces of protein folding--hydrophobicity and conformational entropy--are nonspecific. A long-standing puzzle has, therefore, been: What forces drive the formation of the specific internal architectures in globular proteins? We find that any self-avoiding flexible polymer molecule will develop large amounts of secondary structure, helices and parallel and antiparallel sheets, as it is driven to increasing compactness by any force of attraction among the chain monomers. Thus structure formation arises from the severity of steric constraints in compact polymers. This steric principle of organization can account for why short helices are stable in globular proteins, why there are parallel and anti-parallel sheets in proteins, and why weakly unfolded proteins have some secondary structure. On this basis, it should be possible to construct copolymers, not necessarily using amino acids, that can collapse to maximum compactness in incompatible solvents and that should then have structural organization resembling that of proteins. Images PMID:2385597

A Clash of Cultures: Improving the "Fit" between Evaluative Independence and the Political Requirements of a Democratic Society

ERIC Educational Resources Information Center

Chelimsky, Eleanor

2008-01-01

This article presents a plenary address wherein the author talks about cultural clashes, about what happens when evaluation meets politics. In her address, the author talks about the kinds of clashes that occur on a regular basis between evaluative independence and the political culture it challenges, along with possible ways to predict, parry, or…

The MUSIC of CLASH: Predictions on the Concentration-Mass Relation

NASA Astrophysics Data System (ADS)

Meneghetti, M.; Rasia, E.; Vega, J.; Merten, J.; Postman, M.; Yepes, G.; Sembolini, F.; Donahue, M.; Ettori, S.; Umetsu, K.; Balestra, I.; Bartelmann, M.; Benítez, N.; Biviano, A.; Bouwens, R.; Bradley, L.; Broadhurst, T.; Coe, D.; Czakon, N.; De Petris, M.; Ford, H.; Giocoli, C.; Gottlöber, S.; Grillo, C.; Infante, L.; Jouvel, S.; Kelson, D.; Koekemoer, A.; Lahav, O.; Lemze, D.; Medezinski, E.; Melchior, P.; Mercurio, A.; Molino, A.; Moscardini, L.; Monna, A.; Moustakas, J.; Moustakas, L. A.; Nonino, M.; Rhodes, J.; Rosati, P.; Sayers, J.; Seitz, S.; Zheng, W.; Zitrin, A.

2014-12-01

We present an analysis of the MUSIC-2 N-body/hydrodynamical simulations aimed at estimating the expected concentration-mass relation for the CLASH (Cluster Lensing and Supernova Survey with Hubble) cluster sample. We study nearly 1,400 halos simulated at high spatial and mass resolution. We study the shape of both their density and surface-density profiles and fit them with a variety of radial functions, including the Navarro-Frenk-White (NFW), the generalized NFW, and the Einasto density profiles. We derive concentrations and masses from these fits. We produce simulated Chandra observations of the halos, and we use them to identify objects resembling the X-ray morphologies and masses of the clusters in the CLASH X-ray-selected sample. We also derive a concentration-mass relation for strong-lensing clusters. We find that the sample of simulated halos that resembles the X-ray morphology of the CLASH clusters is composed mainly of relaxed halos, but it also contains a significant fraction of unrelaxed systems. For such a heterogeneous sample we measure an average two-dimensional concentration that is ~11% higher than is found for the full sample of simulated halos. After accounting for projection and selection effects, the average NFW concentrations of CLASH clusters are expected to be intermediate between those predicted in three dimensions for relaxed and super-relaxed halos. Matching the simulations to the individual CLASH clusters on the basis of the X-ray morphology, we expect that the NFW concentrations recovered from the lensing analysis of the CLASH clusters are in the range [3-6], with an average value of 3.87 and a standard deviation of 0.61.

The music of clash: predictions on the concentration-mass relation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meneghetti, M.; Rasia, E.; Vega, J.

We present an analysis of the MUSIC-2 N-body/hydrodynamical simulations aimed at estimating the expected concentration-mass relation for the CLASH (Cluster Lensing and Supernova Survey with Hubble) cluster sample. We study nearly 1,400 halos simulated at high spatial and mass resolution. We study the shape of both their density and surface-density profiles and fit them with a variety of radial functions, including the Navarro-Frenk-White (NFW), the generalized NFW, and the Einasto density profiles. We derive concentrations and masses from these fits. We produce simulated Chandra observations of the halos, and we use them to identify objects resembling the X-ray morphologies andmore » masses of the clusters in the CLASH X-ray-selected sample. We also derive a concentration-mass relation for strong-lensing clusters. We find that the sample of simulated halos that resembles the X-ray morphology of the CLASH clusters is composed mainly of relaxed halos, but it also contains a significant fraction of unrelaxed systems. For such a heterogeneous sample we measure an average two-dimensional concentration that is ∼11% higher than is found for the full sample of simulated halos. After accounting for projection and selection effects, the average NFW concentrations of CLASH clusters are expected to be intermediate between those predicted in three dimensions for relaxed and super-relaxed halos. Matching the simulations to the individual CLASH clusters on the basis of the X-ray morphology, we expect that the NFW concentrations recovered from the lensing analysis of the CLASH clusters are in the range [3-6], with an average value of 3.87 and a standard deviation of 0.61.« less

The Abundance of Large Arcs From CLASH

NASA Astrophysics Data System (ADS)

Xu, Bingxiao; Postman, Marc; Meneghetti, Massimo; Coe, Dan A.; Clash Team

2015-01-01

We have developed an automated arc-finding algorithm to perform a rigorous comparison of the observed and simulated abundance of large lensed background galaxies (a.k.a arcs). We use images from the CLASH program to derive our observed arc abundance. Simulated CLASH images are created by performing ray tracing through mock clusters generated by the N-body simulation calibrated tool -- MOKA, and N-body/hydrodynamic simulations -- MUSIC, over the same mass and redshift range as the CLASH X-ray selected sample. We derive a lensing efficiency of 15 ± 3 arcs per cluster for the X-ray selected CLASH sample and 4 ± 2 arcs per cluster for the simulated sample. The marginally significant difference (3.0 σ) between the results for the observations and the simulations can be explained by the systematically smaller area with magnification larger than 3 (by a factor of ˜4) in both MOKA and MUSIC mass models relative to those derived from the CLASH data. Accounting for this difference brings the observed and simulated arc statistics into full agreement. We find that the source redshift distribution does not have big impact on the arc abundance but the arc abundance is very sensitive to the concentration of the dark matter halos. Our results suggest that the solution to the "arc statistics problem" lies primarily in matching the cluster dark matter distribution.

Modeling and experimental assessment of a buried Leu–Ile mutation in dengue envelope domain III

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kulkarni, Manjiri R.; Numoto, Nobutaka; Ito, Nobutoshi

Envelope protein domain III (ED3) of the dengue virus is important for both antibody binding and host cell interaction. Here, we focused on how a L387I mutation in the protein core could take place in DEN4 ED3, but cannot be accommodated in DEN3 ED3 without destabilizing its structure. To this end, we modeled a DEN4-L387I structure using the Penultimate Rotamer Library and taking the DEN4 ED3 main-chain as a fixed template. We found that three out of seven Ile{sup 387} conformers fit in DEN4 ED3 without introducing the severe atomic clashes that are observed when DEN3 serotype’s ED3 is usedmore » as a template. A more extensive search using 273 side-chain rotamers of the residues surrounding Ile{sup 387} confirmed this prediction. In order to assess the prediction, we determined the crystal structure of DEN4-L387I at 2 Å resolution. Ile{sup 387} indeed adopted one of the three predicted rotamers. Altogether, this study demonstrates that the effects of single mutations are to a large extent successfully predicted by systematically modeling the side-chain structures of the mutated as well as those of its surrounding residues using fixed main-chain structures and assessing inter-atomic steric clashes. More accurate and reliable predictions require considering sub-angstrom main-chain deformation, which remains a challenging task. - Highlights: • We mutated L387I of DEN4 ED3 and examined its effects on structure and stability. • We modeled the side-chain of Ile{sup 387} using DEN4 ED3's structure as a template. • We determined the crystal structure of DEN4-L387I and confirmed the modeling. • Side-chain repacking occurring around Ile{sup 387} involved >3 inter-connected residues. • These results explained why L387I mutation in DEN4 ED3 conserves thermostability.« less

A Generic Self-Assembly Process in Microcompartments and Synthetic Protein Nanotubes.

PubMed

Uddin, Ismail; Frank, Stefanie; Warren, Martin J; Pickersgill, Richard W

2018-05-01

Bacterial microcompartments enclose a biochemical pathway and reactive intermediate within a protein envelope formed by the shell proteins. Herein, the orientation of the propanediol-utilization (Pdu) microcompartment shell protein PduA in bacterial microcompartments and in synthetic nanotubes, and the orientation of PduB in synthetic nanotubes are revealed. When produced individually, PduA hexamers and PduB trimers, tessellate to form flat sheets in the crystal, or they can self-assemble to form synthetic protein nanotubes in solution. Modelling the orientation of PduA in the 20 nm nanotube so as to preserve the shape complementarity and key interactions seen in the crystal structure suggests that the concave surface of the PduA hexamer faces out. This orientation is confirmed experimentally in synthetic nanotubes and in the bacterial microcompartment produced in vivo. The PduB nanotubes described here have a larger diameter, 63 nm, with the concave surface of the trimer again facing out. The conserved concave surface out characteristic of these nano-structures reveals a generic assembly process that causes the interface between adjacent subunits to bend in a common direction that optimizes shape complementarity and minimizes steric clashes. This understanding underpins engineering strategies for the biotechnological application of protein nanotubes. © 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interactions between cycloguanil derivatives and wild type and resistance-associated mutant Plasmodium falciparum dihydrofolate reductases

NASA Astrophysics Data System (ADS)

Maitarad, Phornphimon; Kamchonwongpaisan, Sumalee; Vanichtanankul, Jarunee; Vilaivan, Tirayut; Yuthavong, Yongyuth; Hannongbua, Supa

2009-04-01

Comparative molecular field analysis (CoMFA) and quantum chemical calculations were performed on cycloguanil (Cyc) derivatives of the wild type and the quadruple mutant (Asn51Ile, Cys59Arg, Ser108Asn, Ile164Leu) of Plasmodium falciparum dihydrofolate reductase ( PfDHFR). The represented CoMFA models of wild type ( r_{{cv}}2 = 0.727 and r 2 = 0.985) and mutant type ( r_{{cv}}2 = 0.786 and r 2 = 0.979) can describe the differences of the Cyc structural requirements for the two types of PfDHFR enzymes and can be useful to guide the design of new inhibitors. Moreover, the obtained particular interaction energies between the Cyc and the surrounding residues in the binding pocket indicated that Asn108 of mutant enzyme was the cause of Cyc resistance by producing steric clash with p-Cl of Cyc. Consequently, comparing the energy contributions with the potent flexible WR99210 inhibitor, it was found that the key mutant residue, Asn108, demonstrates attractive interaction with this inhibitor and some residues, Leu46, Ile112, Pro113, Phe116, and Leu119, seem to perform as second binding site with WR99210. Therefore, quantum chemical calculations can be useful for investigating residue interactions to clarify the cause of drug resistance.

NMSim web server: integrated approach for normal mode-based geometric simulations of biologically relevant conformational transitions in proteins.

PubMed

Krüger, Dennis M; Ahmed, Aqeel; Gohlke, Holger

2012-07-01

The NMSim web server implements a three-step approach for multiscale modeling of protein conformational changes. First, the protein structure is coarse-grained using the FIRST software. Second, a rigid cluster normal-mode analysis provides low-frequency normal modes. Third, these modes are used to extend the recently introduced idea of constrained geometric simulations by biasing backbone motions of the protein, whereas side chain motions are biased toward favorable rotamer states (NMSim). The generated structures are iteratively corrected regarding steric clashes and stereochemical constraint violations. The approach allows performing three simulation types: unbiased exploration of conformational space; pathway generation by a targeted simulation; and radius of gyration-guided simulation. On a data set of proteins with experimentally observed conformational changes, the NMSim approach has been shown to be a computationally efficient alternative to molecular dynamics simulations for conformational sampling of proteins. The generated conformations and pathways of conformational transitions can serve as input to docking approaches or more sophisticated sampling techniques. The web server output is a trajectory of generated conformations, Jmol representations of the coarse-graining and a subset of the trajectory and data plots of structural analyses. The NMSim webserver, accessible at http://www.nmsim.de, is free and open to all users with no login requirement.

Platelet factor 4 (CXCL4) seals blood clots by altering the structure of fibrin.

PubMed

Amelot, Aymeric A; Tagzirt, Madjid; Ducouret, Guylaine; Kuen, René Lai; Le Bonniec, Bernard F

2007-01-05

Platelet factor-4 (PF4/CXCL4) is an orphan chemokine released in large quantities in the vicinity of growing blood clots. Coagulation of plasma supplemented with a matching amount of PF4 results in a translucent jelly-like clot. Saturating amounts of PF4 reduce the porosity of the fibrin network 4.4-fold and decrease the values of the elastic and loss moduli by 31- and 59-fold, respectively. PF4 alters neither the cleavage of fibrinogen by thrombin nor the cross-linking of protofibrils by activated factor XIII but binds to fibrin and dramatically transforms the structure of the ensuing network. Scanning electron microscopy showed that PF4 gives rise to a previously unreported pattern of polymerization where fibrin assembles to form a sealed network. The subunits constituting PF4 form a tetrahedron having at its corners a RPRH motif that mimics (in reverse orientation) the Gly-His-Arg-Pro-amide peptides that co-crystallize with fibrin. Molecular modeling showed that PF4 could be docked to fibrin with remarkable complementarities and absence of steric clashes, allowing the assembly of irregular polymers. Consistent with this hypothesis, as little as 50 microm the QVRPRHIT peptide derived from PF4 affects the polymerization of fibrin.

New Additions to the ClusPro Server Motivated by CAPRI

PubMed Central

Vajda, Sandor; Yueh, Christine; Beglov, Dmitri; Bohnuud, Tanggis; Mottarella, Scott E.; Xia, Bing; Hall, David R.; Kozakov, Dima

2016-01-01

The heavily used protein-protein docking server ClusPro performs three computational steps as follows: (1) rigid body docking, (2) RMSD based clustering of the 1000 lowest energy structures, and (3) the removal of steric clashes by energy minimization. In response to challenges encountered in recent CAPRI targets, we added three new options to ClusPro. These are (1) accounting for Small Angle X-ray Scattering (SAXS) data in docking; (2) considering pairwise interaction data as restraints; and (3) enabling discrimination between biological and crystallographic dimers. In addition, we have developed an extremely fast docking algorithm based on 5D rotational manifold FFT, and an algorithm for docking flexible peptides that include known sequence motifs. We feel that these developments will further improve the utility of ClusPro. However, CAPRI emphasized several shortcomings of the current server, including the problem of selecting the right energy parameters among the five options provided, and the problem of selecting the best models among the 10 generated for each parameter set. In addition, results convinced us that further development is needed for docking homology models. Finally we discuss the difficulties we have encountered when attempting to develop a refinement algorithm that would be computationally efficient enough for inclusion in a heavily used server. PMID:27936493

Structural basis for the recognition of Asef by adenomatous polyposis coli

PubMed Central

Zhang, Zhenyi; Chen, Leyi; Gao, Lei; Lin, Kui; Zhu, Liang; Lu, Yang; Shi, Xiaoshan; Gao, Yuan; Zhou, Jing; Xu, Ping; Zhang, Jian; Wu, Geng

2012-01-01

Adenomatous polyposis coli (APC) regulates cell-cell adhesion and cell migration through activating the APC-stimulated guanine nucleotide-exchange factor (GEF; Asef), which is usually autoinhibited through the binding between its Src homology 3 (SH3) and Dbl homology (DH) domains. The APC-activated Asef stimulates the small GTPase Cdc42, which leads to decreased cell-cell adherence and enhanced cell migration. In colorectal cancers, truncated APC constitutively activates Asef and promotes cancer cell migration and angiogenesis. Here, we report crystal structures of the human APC/Asef complex. We find that the armadillo repeat domain of APC uses a highly conserved surface groove to recognize the APC-binding region (ABR) of Asef, conformation of which changes dramatically upon binding to APC. Key residues on APC and Asef for the complex formation were mutated and their importance was demonstrated by binding and activity assays. Structural superimposition of the APC/Asef complex with autoinhibited Asef suggests that the binding between APC and Asef might create a steric clash between Asef-DH domain and APC, which possibly leads to a conformational change in Asef that stimulates its GEF activity. Our structures thus elucidate the molecular mechanism of Asef recognition by APC, as well as provide a potential target for pharmaceutical intervention against cancers. PMID:21788986

Architecture with GIDEON, A Program for Design in Structural DNA Nanotechnology

PubMed Central

Birac, Jeffrey J.; Sherman, William B.; Kopatsch, Jens; Constantinou, Pamela E.; Seeman, Nadrian C.

2012-01-01

We present geometry based design strategies for DNA nanostructures. The strategies have been implemented with GIDEON – a Graphical Integrated Development Environment for OligoNucleotides. GIDEON has a highly flexible graphical user interface that facilitates the development of simple yet precise models, and the evaluation of strains therein. Models are built on a simple model of undistorted B-DNA double-helical domains. Simple point and click manipulations of the model allow the minimization of strain in the phosphate-backbone linkages between these domains and the identification of any steric clashes that might occur as a result. Detailed analysis of 3D triangles yields clear predictions of the strains associated with triangles of different sizes. We have carried out experiments that confirm that 3D triangles form well only when their geometrical strain is less than 4% deviation from the estimated relaxed structure. Thus geometry-based techniques alone, without energetic considerations, can be used to explain general trends in DNA structure formation. We have used GIDEON to build detailed models of double crossover and triple crossover molecules, evaluating the non-planarity associated with base tilt and junction mis-alignments. Computer modeling using a graphical user interface overcomes the limited precision of physical models for larger systems, and the limited interaction rate associated with earlier, command-line driven software. PMID:16630733

KOSMOS: a universal morph server for nucleic acids, proteins and their complexes.

PubMed

Seo, Sangjae; Kim, Moon Ki

2012-07-01

KOSMOS is the first online morph server to be able to address the structural dynamics of DNA/RNA, proteins and even their complexes, such as ribosomes. The key functions of KOSMOS are the harmonic and anharmonic analyses of macromolecules. In the harmonic analysis, normal mode analysis (NMA) based on an elastic network model (ENM) is performed, yielding vibrational modes and B-factor calculations, which provide insight into the potential biological functions of macromolecules based on their structural features. Anharmonic analysis involving elastic network interpolation (ENI) is used to generate plausible transition pathways between two given conformations by optimizing a topology-oriented cost function that guarantees a smooth transition without steric clashes. The quality of the computed pathways is evaluated based on their various facets, including topology, energy cost and compatibility with the NMA results. There are also two unique features of KOSMOS that distinguish it from other morph servers: (i) the versatility in the coarse-graining methods and (ii) the various connection rules in the ENM. The models enable us to analyze macromolecular dynamics with the maximum degrees of freedom by combining a variety of ENMs from full-atom to coarse-grained, backbone and hybrid models with one connection rule, such as distance-cutoff, number-cutoff or chemical-cutoff. KOSMOS is available at http://bioengineering.skku.ac.kr/kosmos.

Islamic Resurgence in Turkey? An Analysis of Political and Social Elements

DTIC Science & Technology

1993-06-01

groups 199 "’ Radical Right ’ Preparing For Clashes With PKK," Paris AFP, FBIS, 9 Jul 92, and "Youth Organization Prepares To Clash With PKK," SABAH...Party Leader." Ankara Turkiye Radyolari Network. Foreian Broadcast Information Service. 21 Oct 91. "’ Radical Right ’ Preparing For Clashes With PKK...the nature of these murders. First, the targets for this violence are essentially all ethnic Kurds. Second, they are all considered by the radical

The dark side of risk and crisis communication: legal conflicts and responsibility allocation

NASA Astrophysics Data System (ADS)

Scolobig, A.

2015-04-01

Inadequate, misinterpreted or missing risk and crisis communication may be a reason for practitioners, and sometimes even science advisors, to become subjects of criminal charges. This work discusses the legal consequences of communication. After presenting some cases, the discussion focuses on three critical issues: the development of effective communication protocols; the role, tasks and responsibilities of science advisors; and the collateral effects of practitioners' defensive behaviours. For example, if the avoidance of personal liability becomes a primary objective for practitioners, it may clash with other objectives, such as the protection of vulnerable communities or the transparency of decision-making. The conclusion presents some ideas for future research on the legal aspects of risk communication.

Fast, clash-free RNA conformational morphing using molecular junctions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heliou, Amelie; Budday, Dominik; Fonseca, Rasmus

Non-coding ribonucleic acids (ncRNA) are functional RNA molecules that are not translated into protein. They are extremely dynamic, adopting diverse conformational substates, which enables them to modulate their interaction with a large number of other molecules. The flexibility of ncRNA provides a challenge for probing their complex 3D conformational landscape, both experimentally and computationally. As a result, despite their conformational diversity, ncRNAs mostly preserve their secondary structure throughout the dynamic ensemble. Here we present a kinematics-based procedure to morph an RNA molecule between conformational substates, while avoiding inter-atomic clashes. We represent an RNA as a kinematic linkage, with fixed groupsmore » of atoms as rigid bodies and rotatable bonds as degrees of freedom. Our procedure maintains RNA secondary structure by treating hydrogen bonds between base pairs as constraints. The constraints define a lower-dimensional, secondary-structure constraint manifold in conformation space, where motions are largely governed by molecular junctions of unpaired nucleotides. On a large benchmark set, we show that our morphing procedure compares favorably to peer algorithms, and can approach goal conformations to within a low all-atom RMSD by directing fewer than 1% of its atoms. Furthermore, our results suggest that molecular junctions can modulate 3D structural rearrangements, while secondary structure elements guide large parts of the molecule along the transition to the correct final conformation.« less

Fast, clash-free RNA conformational morphing using molecular junctions

DOE PAGES

Heliou, Amelie; Budday, Dominik; Fonseca, Rasmus; ...

2017-03-13

Non-coding ribonucleic acids (ncRNA) are functional RNA molecules that are not translated into protein. They are extremely dynamic, adopting diverse conformational substates, which enables them to modulate their interaction with a large number of other molecules. The flexibility of ncRNA provides a challenge for probing their complex 3D conformational landscape, both experimentally and computationally. As a result, despite their conformational diversity, ncRNAs mostly preserve their secondary structure throughout the dynamic ensemble. Here we present a kinematics-based procedure to morph an RNA molecule between conformational substates, while avoiding inter-atomic clashes. We represent an RNA as a kinematic linkage, with fixed groupsmore » of atoms as rigid bodies and rotatable bonds as degrees of freedom. Our procedure maintains RNA secondary structure by treating hydrogen bonds between base pairs as constraints. The constraints define a lower-dimensional, secondary-structure constraint manifold in conformation space, where motions are largely governed by molecular junctions of unpaired nucleotides. On a large benchmark set, we show that our morphing procedure compares favorably to peer algorithms, and can approach goal conformations to within a low all-atom RMSD by directing fewer than 1% of its atoms. Furthermore, our results suggest that molecular junctions can modulate 3D structural rearrangements, while secondary structure elements guide large parts of the molecule along the transition to the correct final conformation.« less

Dynamics of living matter: can we ``see'' collective motions in proteins?

NASA Astrophysics Data System (ADS)

Hekstra, Doeke

2015-03-01

Proteins are ideal model systems for quantitative study of the interplay of physical and evolutionary forces. Collective, anharmonic motions of amino acid residues within proteins are thought to be central to their function, and to explain, in large part, the complex dependence of protein function on its constituent parts. Currently, the experimental characterization of such motions poses a major stumbling block on the way to a physical understanding of protein function and evolution. We are addressing this problem in two ways. First, alternate conformations of protein residues can often be distinguished in the electron density estimated from room-temperature X-ray crystallography. The dense packing of residues in the folded protein requires that such conformational variations must propagate through networks of amino acids to preclude local steric clashes. Fraser and colleagues showed that such steric conflicts can be used to extract contact networks of residues collectively switching conformation. We ask if these networks are conserved over homologous sequences and connected to the functional reaction coordinate, both of which would demonstrate their fundamental importance. I will describe initial results for the family of PDZ domains: small ligand-binding proteins for which a network of energetically and conformationally coupled residues controlling ligand affinity has been demonstrated previously by a range of methods. Second, the analysis of collective motions in proteins, by nearly any means, is indirect: nothing is seen moving. To directly induce and ``see'' motions on a range of time scales, we developed a new approach based on (a) electric field pulses to induce motions within a protein crystal and (b) time-resolved crystallography to observe these motions. Since proteins generically have a heterogeneous, modifiable charge distribution, this method could provide a powerful, general way of probing the collective motions, and excited states, of proteins in kinetic and atomic detail. I will present initial experiments showing the method is feasible. Taken together, these experiments begin to provide a basis for the development of a physical theory of proteins consistent with their function and adaptation - the source of their survival throughout the evolutionary process.

On the asserted clash between the Freud and the Bianchi identities

NASA Astrophysics Data System (ADS)

Antoci, S.

1995-09-01

Through a constructive method it is shown that the claim advanced in recent times about a clash that should occur between the Freud and the Bianchi identities in Einstein's general theory of relativity is based on a faulty argument.

Sex Education in the Public Schools: A Clash of Religious Freedom and the General Welfare.

ERIC Educational Resources Information Center

First, Patricia F.

1992-01-01

Court litigation, state legislation, school board policy, and public opinion clash over sex education in public schools. However, rising teen pregnancy rates and AIDS make the availability of uncensored health and sex information in schools a necessity. (SK)

Brief Communication: The dark side of risk and crisis communication: legal conflicts and responsibility allocation

NASA Astrophysics Data System (ADS)

Scolobig, A.

2015-06-01

Inadequate, misinterpreted, or missing risk and crisis communication may be a reason for practitioners, and sometimes science advisors, to become the subjects of criminal investigations. This work discusses the legal consequences of inadequate risk communication in these situations. After presenting some cases, the discussion focuses on three critical issues: the development of effective communication protocols; the role, tasks, and responsibilities of science advisors; and the collateral effects of practitioners' defensive behaviours. For example, if the avoidance of personal liability becomes a primary objective for practitioners, it may clash with other objectives, such as the protection of vulnerable communities or the transparency of decision making. The conclusion presents some ideas for future research on the legal aspects of risk communication.

Assembly and analysis of eukaryotic Argonaute–RNA complexes in microRNA-target recognition

PubMed Central

Gan, Hin Hark; Gunsalus, Kristin C.

2015-01-01

Experimental studies have uncovered a variety of microRNA (miRNA)–target duplex structures that include perfect, imperfect and seedless duplexes. However, non-canonical binding modes from imperfect/seedless duplexes are not well predicted by computational approaches, which rely primarily on sequence and secondary structural features, nor have their tertiary structures been characterized because solved structures to date are limited to near perfect, straight duplexes in Argonautes (Agos). Here, we use structural modeling to examine the role of Ago dynamics in assembling viable eukaryotic miRNA-induced silencing complexes (miRISCs). We show that combinations of low-frequency, global modes of motion of Ago domains are required to accommodate RNA duplexes in model human and C. elegans Ago structures. Models of viable miRISCs imply that Ago adopts variable conformations at distinct target sites that generate distorted, imperfect miRNA-target duplexes. Ago's ability to accommodate a duplex is dependent on the region where structural distortions occur: distortions in solvent-exposed seed and 3′-end regions are less likely to produce steric clashes than those in the central duplex region. Energetic analyses of assembled miRISCs indicate that target recognition is also driven by favorable Ago-duplex interactions. Such structural insights into Ago loading and target recognition mechanisms may provide a more accurate assessment of miRNA function. PMID:26432829

Molecular basis for the unique deubiquitinating activity of the NF-kappaB inhibitor A20.

PubMed

Lin, Su-Chang; Chung, Jee Y; Lamothe, Betty; Rajashankar, Kanagalaghatta; Lu, Miao; Lo, Yu-Chih; Lam, Amy Y; Darnay, Bryant G; Wu, Hao

2008-02-15

Nuclear factor kappaB (NF-kappaB) activation in tumor necrosis factor, interleukin-1, and Toll-like receptor pathways requires Lys63-linked nondegradative polyubiquitination. A20 is a specific feedback inhibitor of NF-kappaB activation in these pathways that possesses dual ubiquitin-editing functions. While the N-terminal domain of A20 is a deubiquitinating enzyme (DUB) for Lys63-linked polyubiquitinated signaling mediators such as TRAF6 and RIP, its C-terminal domain is a ubiquitin ligase (E3) for Lys48-linked degradative polyubiquitination of the same substrates. To elucidate the molecular basis for the DUB activity of A20, we determined its crystal structure and performed a series of biochemical and cell biological studies. The structure reveals the potential catalytic mechanism of A20, which may be significantly different from papain-like cysteine proteases. Ubiquitin can be docked onto a conserved A20 surface; this interaction exhibits charge complementarity and no steric clash. Surprisingly, A20 does not have specificity for Lys63-linked polyubiquitin chains. Instead, it effectively removes Lys63-linked polyubiquitin chains from TRAF6 without dissembling the chains themselves. Our studies suggest that A20 does not act as a general DUB but has the specificity for particular polyubiquitinated substrates to assure its fidelity in regulating NF-kappaB activation in the tumor necrosis factor, interleukin-1, and Toll-like receptor pathways.

New additions to the ClusPro server motivated by CAPRI.

PubMed

Vajda, Sandor; Yueh, Christine; Beglov, Dmitri; Bohnuud, Tanggis; Mottarella, Scott E; Xia, Bing; Hall, David R; Kozakov, Dima

2017-03-01

The heavily used protein-protein docking server ClusPro performs three computational steps as follows: (1) rigid body docking, (2) RMSD based clustering of the 1000 lowest energy structures, and (3) the removal of steric clashes by energy minimization. In response to challenges encountered in recent CAPRI targets, we added three new options to ClusPro. These are (1) accounting for small angle X-ray scattering data in docking; (2) considering pairwise interaction data as restraints; and (3) enabling discrimination between biological and crystallographic dimers. In addition, we have developed an extremely fast docking algorithm based on 5D rotational manifold FFT, and an algorithm for docking flexible peptides that include known sequence motifs. We feel that these developments will further improve the utility of ClusPro. However, CAPRI emphasized several shortcomings of the current server, including the problem of selecting the right energy parameters among the five options provided, and the problem of selecting the best models among the 10 generated for each parameter set. In addition, results convinced us that further development is needed for docking homology models. Finally, we discuss the difficulties we have encountered when attempting to develop a refinement algorithm that would be computationally efficient enough for inclusion in a heavily used server. Proteins 2017; 85:435-444. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

KOSMOS: a universal morph server for nucleic acids, proteins and their complexes

PubMed Central

Seo, Sangjae; Kim, Moon Ki

2012-01-01

KOSMOS is the first online morph server to be able to address the structural dynamics of DNA/RNA, proteins and even their complexes, such as ribosomes. The key functions of KOSMOS are the harmonic and anharmonic analyses of macromolecules. In the harmonic analysis, normal mode analysis (NMA) based on an elastic network model (ENM) is performed, yielding vibrational modes and B-factor calculations, which provide insight into the potential biological functions of macromolecules based on their structural features. Anharmonic analysis involving elastic network interpolation (ENI) is used to generate plausible transition pathways between two given conformations by optimizing a topology-oriented cost function that guarantees a smooth transition without steric clashes. The quality of the computed pathways is evaluated based on their various facets, including topology, energy cost and compatibility with the NMA results. There are also two unique features of KOSMOS that distinguish it from other morph servers: (i) the versatility in the coarse-graining methods and (ii) the various connection rules in the ENM. The models enable us to analyze macromolecular dynamics with the maximum degrees of freedom by combining a variety of ENMs from full-atom to coarse-grained, backbone and hybrid models with one connection rule, such as distance-cutoff, number-cutoff or chemical-cutoff. KOSMOS is available at http://bioengineering.skku.ac.kr/kosmos. PMID:22669912

On the Clash of Martyrological Memories

ERIC Educational Resources Information Center

Jansen, Jonathan D.

2009-01-01

What happens when students holding rival though indirect memories of past conflicts confront each other in the same classroom? What are the kinds of political and pedagogical approaches necessary for mediating such "clashes of martyrological memories" in the same educational space? And why is critical theory inept at offering resolutions…

Law of Empires.

ERIC Educational Resources Information Center

Martz, Carlton

2001-01-01

This issue of "Bill of Rights in Action" explores issues raised by empires and imperial law. The first article, "Clash of Empires: The Fight for North America," looks at the clash of empires and the fight for North America during the 18th century. The second article, "When Roman Law Ruled the Western World," examines…

Bioethics and international human rights.

PubMed

Thomasma, D C

1997-01-01

Noting how the spread of medical technology is creating clashes with traditional values and within cultures, the author addresses the clash between Western rights-based incentives, as used by the United Nations to guarantee respect for life and dignity, and communitarian traditions. He proposes a mean between wholesale cultural relativism and international absolutism.

Juvenile Justice and a Strengths Perspective: Complement or Clash?

ERIC Educational Resources Information Center

Clark, Michael D.

2009-01-01

Does the new realm of positive psychology and strength-based strategies complement or clash with the remedial discipline of social control traditionally practiced in juvenile justice programs? Many welcome the balance of positive psychology, the strengths perspective, and coping and resilience studies. Although emerging from different disciplines,…

2007 NCTE Presidential Address: Where Ignorant Armies Clash by Night

ERIC Educational Resources Information Center

Yatvin, Joanne

2008-01-01

This article presents the text of Joanne Yatvin's presidential address, delivered at the NCTE Annual Convention in New York City in November 2007. The title of her presidential address, "Where Ignorant Armies Clash by Night," was taken from Matthew Arnold's (1867) poem "Dover Beach." Yatvin states that the federal government…

More than Beliefs: Subject Areas and Teachers' Integration of Laptops in Secondary Teaching

ERIC Educational Resources Information Center

Howard, Sarah K.; Chan, Amy; Caputi, Peter

2015-01-01

The purpose of this paper is to explore the relationship of subject areas to teachers' technology integration. Educational technology research has often identified "culture clashes" to explain differences in technology use between subject areas. These clashes are frequently attributed to core features, values and beliefs held in the…

A Feminist Perspective on Technical Communicative Action: Exploring How Alternative Worldviews Affect Environmental Remediation Efforts.

ERIC Educational Resources Information Center

Ross, Susan Mallon

1994-01-01

Describes the current practices in public environmental debate and reform movements as relevant to technical communicators. Reviews a case in which the Mohawk community clashed with the Environmental Protection Agency. Explores the clash of worldviews and shows how a feminist perspective might aid in such a conflict. (HB)

Beyond the Social Imaginary of "Clash of Civilizations"?

ERIC Educational Resources Information Center

Rizvi, Fazal

2011-01-01

In recent years, the notion of a "clash of civilizations", first put forward by Samuel Huntington (1996), has been widely used to explain the contemporary dynamics of geo-political conflict. It has been argued that the fundamental source of conflict is no longer primarily ideological, or even economic, but cultural. Despite many trenchant and…

The Detection and Statistics of Giant Arcs behind CLASH Clusters

NASA Astrophysics Data System (ADS)

Xu, Bingxiao; Postman, Marc; Meneghetti, Massimo; Seitz, Stella; Zitrin, Adi; Merten, Julian; Maoz, Dani; Frye, Brenda; Umetsu, Keiichi; Zheng, Wei; Bradley, Larry; Vega, Jesus; Koekemoer, Anton

2016-02-01

We developed an algorithm to find and characterize gravitationally lensed galaxies (arcs) to perform a comparison of the observed and simulated arc abundance. Observations are from the Cluster Lensing And Supernova survey with Hubble (CLASH). Simulated CLASH images are created using the MOKA package and also clusters selected from the high-resolution, hydrodynamical simulations, MUSIC, over the same mass and redshift range as the CLASH sample. The algorithm's arc elongation accuracy, completeness, and false positive rate are determined and used to compute an estimate of the true arc abundance. We derive a lensing efficiency of 4 ± 1 arcs (with length ≥6″ and length-to-width ratio ≥7) per cluster for the X-ray-selected CLASH sample, 4 ± 1 arcs per cluster for the MOKA-simulated sample, and 3 ± 1 arcs per cluster for the MUSIC-simulated sample. The observed and simulated arc statistics are in full agreement. We measure the photometric redshifts of all detected arcs and find a median redshift zs = 1.9 with 33% of the detected arcs having zs > 3. We find that the arc abundance does not depend strongly on the source redshift distribution but is sensitive to the mass distribution of the dark matter halos (e.g., the c-M relation). Our results show that consistency between the observed and simulated distributions of lensed arc sizes and axial ratios can be achieved by using cluster-lensing simulations that are carefully matched to the selection criteria used in the observations.

Google Scholar: The 800-Pound Gorilla in the Room

ERIC Educational Resources Information Center

Shapiro, Steven

2012-01-01

There is a "clash of civilizations" going on in the information field--a clash characterized by a brash upstart, Google, and its attendant creations, Google Scholar and Google Books, and the old guard represented by the library world. Librarians who deprecate Google Scholar or simply ignore the Google phenomenon do so at their own risk. Google…

When Expectations Clash: Vocational Education at the Intersection of Workplace and School

ERIC Educational Resources Information Center

Tyson, Ruhi

2016-01-01

Next to highly regarded varieties of apprenticeship-based vocational education there are, in many countries, forms of mainly school-based VET (vocational education and training) that suffer from a clash of expectations between schools and workplaces as sites of vocational education. School-based VET is viewed as of lesser value compared to work…

Clash of the Titans

ERIC Educational Resources Information Center

Subramaniam, Karthigeyan

2010-01-01

WebQuests and the 5E learning cycle are titans of the science classroom. These popular inquiry-based strategies are most often used as separate entities, but the author has discovered that using a combined WebQuest and 5E learning cycle format taps into the inherent power and potential of both strategies. In the lesson, "Clash of the Titans,"…

Islamic Fatalism and the Clash of Civilizations: An Appraisal of a Contentious and Dubious Theory

ERIC Educational Resources Information Center

Acevedo, Gabriel A.

2008-01-01

This paper will address the question of Islamic fatalism. Survey data will be used to assess Samuel P. Huntington's controversial "Clash of Civilizations" thesis and its emphasis on fatalism as an inherent characteristic of Islamic religion. The concept of fatalism is expanded and theorized as a function of both structural and…

Why the CLASH model is an unconvincing evolutionary theory of crime.

PubMed

Boutwell, Brian B; Winegard, Bo

2017-01-01

The CLASH model is not convincing for two reasons. First, it ignores prior research proposing very similar ideas in a more compelling fashion. Second, it dismisses the role of genetic factors in shaping criminal propensities across population groups, opting for a facultative view of life history evolution that does not seem to square with current evidence.

THE DETECTION AND STATISTICS OF GIANT ARCS BEHIND CLASH CLUSTERS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Bingxiao; Zheng, Wei; Postman, Marc

We developed an algorithm to find and characterize gravitationally lensed galaxies (arcs) to perform a comparison of the observed and simulated arc abundance. Observations are from the Cluster Lensing And Supernova survey with Hubble (CLASH). Simulated CLASH images are created using the MOKA package and also clusters selected from the high-resolution, hydrodynamical simulations, MUSIC, over the same mass and redshift range as the CLASH sample. The algorithm's arc elongation accuracy, completeness, and false positive rate are determined and used to compute an estimate of the true arc abundance. We derive a lensing efficiency of 4 ± 1 arcs (with length ≥6″ andmore » length-to-width ratio ≥7) per cluster for the X-ray-selected CLASH sample, 4 ± 1 arcs per cluster for the MOKA-simulated sample, and 3 ± 1 arcs per cluster for the MUSIC-simulated sample. The observed and simulated arc statistics are in full agreement. We measure the photometric redshifts of all detected arcs and find a median redshift z{sub s} = 1.9 with 33% of the detected arcs having z{sub s} > 3. We find that the arc abundance does not depend strongly on the source redshift distribution but is sensitive to the mass distribution of the dark matter halos (e.g., the c–M relation). Our results show that consistency between the observed and simulated distributions of lensed arc sizes and axial ratios can be achieved by using cluster-lensing simulations that are carefully matched to the selection criteria used in the observations.« less

Injury patterns in clashes between citizens and security forces during forced evacuation.

PubMed

Schwartz, D; Bar-Dayan, Y

2008-10-01

Clashes between state security forces and civilian populations can lead to mass casualty incidents (MCI), challenging emergency medical service (EMS) systems, hospitals and medical management systems. In January 2006, clashes erupted between Israeli security forces and settlers, around the forced evacuation of the Amona outpost. Data collected during the events and in subsequent formal debriefings were processed to identify the specifics of an MCI caused by forced evacuation. Pre-event preparedness, time and types of injuries encountered were evaluated among evacuated civilians and security forces members, their transport to hospitals, care received and follow-up. The event is described according to DISAST-CIR methodology. Data were entered on MS Excel (2003) and analysis was carried out using SPSS version 12. 4000 police personnel (backed by army forces) clashed for 12 h with approximately 5000 settlers. 229 injured (174 settlers and 55 security personnel) were cared for at six receiving hospitals. A total of 16 were evacuated by aeromedical evacuation, including one severely head-injured policeman. Settlers used sticks, stones and cement blocks, whereas police used mounted riders, batons and shields. Head injuries were the most common injuries among settlers (50%), whereas extremity injuries dominated among security forces members (72.7%). Large-scale clashes between state security forces and citizens may cause numerous injuries, even if firearms and explosives are not used. Despite the fact that almost all injuries were mild, the incident burdened local medical teams, EMS and Jerusalem hospitals. A predominance of head injuries was found among injured settlers and extremity injuries among injured security forces.

Synthesis of 4′-aminopantetheine and derivatives to probe aminoglycoside N-6′-acetyltransferase

PubMed Central

Yan, Xuxu; Akinnusi, T. Olukayode; Larsen, Aaron T.; Auclair, Karine

2011-01-01

Summary A convenient synthesis of 4′-aminopantetheine from commercial D-pantethine is reported. The amino group was introduced by reductive amination in order to avoid substitution at a sterically congested position. Derivatives of 4′-aminopantetheine were also prepared to evaluate the effect of O-to-N substitution on inhibitors of the resistance-causing enzyme aminoglycoside N-6′-acetyltransferase. The biological results combined with docking studies indicate that in spite of its reported unusual flexibility and ability to adopt different folds, this enzyme is highly specific for AcCoA. PMID:21225062

Clashing Values: A Longitudinal, Exploratory Study of Student Beliefs about General Education, Vocationalism, and Transfer of Learning

ERIC Educational Resources Information Center

Driscoll, Dana Lynn

2014-01-01

One challenge with general education is the often- clashing goal of vocationalism, or educating for the purpose a specific careers or professions. Through a series of longitudinal interviews spanning a group of 14 students' second and fourth semesters at a public, regional research university, the author examines the intersection of beliefs and…

"A Clash of Two Worlds"; Disjuncture between the Norms and Values Held by Educational Practitioners and Parents of Children with Behavioural, Emotional and Social Difficulties

ERIC Educational Resources Information Center

Broomhead, Karen

2014-01-01

This article, by Karen Broomhead of Liverpool John Moores University, discusses an exploration of the clashing norms, values and expectations of parenting behaviours between parents of children with behavioural, emotional and social difficulties (BESD) and practitioners. Semi-structured interviews with 15 education professionals, employed in both…

Argument and Visual Structuring in the 1984 Mondale-Reagan Debates: The Medium's Influence on the Perception of Clash.

ERIC Educational Resources Information Center

Morello, John T.

1988-01-01

Analyzes the visual and verbal content of the 1984 televised debates between Walter Mondale and Ronald Reagan. Asserts that the televised depiction of the debates visually structured portions of them in a manner inconsistent with their verbal content. Focuses on clash, when candidates engaged in arguments of attack or defense. (MS)

"A Zone of Deep Shadow": Pedagogical and Familial Reflections on "The Clash of Civilizations"

ERIC Educational Resources Information Center

Jardine, David W.; Naqvi, Rahat; Jardine, Eric; Zaidi, Ahmad

2010-01-01

This paper examines the media coverage of the murder of a young Muslim girl in Mississauga, Ontario in December 2007. We examine how that coverage moved from concerns for a terrible family event to the use of the language of Samuel Huntington's "Clash of Civilizations." We explore the nature of this exaggeration that occurs in times of…

Narcissistic Force Meets Systemic Resistance: The Energy Clash Model.

PubMed

Sedikides, Constantine; Campbell, W Keith

2017-05-01

This article focuses on the interplay between narcissistic leaders and organizations. It attempts to capture the gist of this interplay with a model outlining the narcissistic organizational trajectory. The Energy Clash Model borrows and adapts a phase/state physics metaphor to conceptualize narcissism as a force that enters or emerges in a stable system (i.e., organization) as a leader, destabilizes it, and stabilizes it at a different state or is expelled. The model consists of three time-contingent phases: perturbation, conflict, and resolution. Narcissists create instability through waves of excitement, proposed reforms, and an inspiring vision for organization's future ( perturbation). With the passage of time, though, systemic awareness and alertness intensify, as organizational costs-in terms of human resources and monetary losses-accrue. Narcissistic energy clashes directly with the organization ( conflict), a clash likely to restabilize the system eventually. The conflict may provoke the exit of the narcissistic leader or his or her accommodation, that is, steps or controls negotiated between the system and the leader ( resolution). Although narcissism is subject to organizational liability, narcissistic energy, when managed and directed properly, may contribute to organizational innovation and evolution. Thus, several interventions for working with narcissistic leaders are discussed.

Structure of a novel antibacterial toxin that exploits elongation factor Tu to cleave specific transfer RNAs

DOE PAGES

Michalska, Karolina; Gucinski, Grant C.; Garza-Sanchez, Fernando; ...

2017-08-11

Contact-dependent growth inhibition (CDI) is a mechanism of inter-cellular competition in which Gram-negative bacteria exchange polymorphic toxins using type V secretion systems. Here, we present structures of the CDI toxin from Escherichia coli NC101 in ternary complex with its cognate immunity protein and elongation factor Tu (EF-Tu). The toxin binds exclusively to domain 2 of EF-Tu, partially overlapping the site that interacts with the 3'-end of aminoacyl-tRNA (aa-tRNA). The toxin exerts a unique ribonuclease activity that cleaves the single-stranded 3'-end from tRNAs that contain guanine discriminator nucleotides. EF-Tu is required to support this tRNase activity in vitro, suggesting the toxinmore » specifically cleaves substrate in the context of GTP·EF-Tu·aa-tRNA complexes. However, superimposition of the toxin domain onto previously solved GTP·EF-Tu·aa-tRNA structures reveals potential steric clashes with both aa-tRNA and the switch I region of EF-Tu. Further, the toxin induces conformational changes in EF-Tu, displacing a β-hairpin loop that forms a critical salt-bridge contact with the 3'-terminal adenylate of aa-tRNA. Altogether, these observations suggest that the toxin remodels GTP·EF-Tu·aa-tRNA complexes to free the 3'-end of aa-tRNA for entry into the nuclease active site.« less

Structure of a novel antibacterial toxin that exploits elongation factor Tu to cleave specific transfer RNAs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michalska, Karolina; Gucinski, Grant C.; Garza-Sanchez, Fernando

Contact-dependent growth inhibition (CDI) is a mechanism of inter-cellular competition in which Gram-negative bacteria exchange polymorphic toxins using type V secretion systems. Here, we present structures of the CDI toxin from Escherichia coli NC101 in ternary complex with its cognate immunity protein and elongation factor Tu (EF-Tu). The toxin binds exclusively to domain 2 of EF-Tu, partially overlapping the site that interacts with the 3'-end of aminoacyl-tRNA (aa-tRNA). The toxin exerts a unique ribonuclease activity that cleaves the single-stranded 3'-end from tRNAs that contain guanine discriminator nucleotides. EF-Tu is required to support this tRNase activity in vitro, suggesting the toxinmore » specifically cleaves substrate in the context of GTP·EF-Tu·aa-tRNA complexes. However, superimposition of the toxin domain onto previously solved GTP·EF-Tu·aa-tRNA structures reveals potential steric clashes with both aa-tRNA and the switch I region of EF-Tu. Further, the toxin induces conformational changes in EF-Tu, displacing a β-hairpin loop that forms a critical salt-bridge contact with the 3'-terminal adenylate of aa-tRNA. Altogether, these observations suggest that the toxin remodels GTP·EF-Tu·aa-tRNA complexes to free the 3'-end of aa-tRNA for entry into the nuclease active site.« less

Structural basis for drug and substrate specificity exhibited by FIV encoding a chimeric FIV/HIV protease

PubMed Central

Lin, Ying-Chuan; Perryman, Alexander L.; Olson, Arthur J.; Torbett, Bruce E.; Elder, John H.; Stout, C. David

2011-01-01

A chimeric feline immunodeficiency virus (FIV) protease (PR) has been engineered that supports infectivity but confers sensitivity to the human immunodeficiency virus (HIV) PR inhibitors darunavir (DRV) and lopinavir (LPV). The 6s-98S PR has five replacements mimicking homologous residues in HIV PR and a sixth which mutated from Pro to Ser during selection. Crystal structures of the 6s-98S FIV PR chimera with DRV and LPV bound have been determined at 1.7 and 1.8 Å resolution, respectively. The structures reveal the role of a flexible 90s loop and residue 98 in supporting Gag processing and infectivity and the roles of residue 37 in the active site and residues 55, 57 and 59 in the flap in conferring the ability to specifically recognize HIV PR drugs. Specifically, Ile37Val preserves tertiary structure but prevents steric clashes with DRV and LPV. Asn55Met and Val59Ile induce a distinct kink in the flap and a new hydrogen bond to DRV. Ile98Pro→Ser and Pro100Asn increase 90s loop flexibility, Gln99Val contributes hydrophobic contacts to DRV and LPV, and Pro100Asn forms compensatory hydrogen bonds. The chimeric PR exhibits a comparable number of hydrogen bonds, electrostatic interactions and hydrophobic contacts with DRV and LPV as in the corresponding HIV PR complexes, consistent with IC50 values in the nanomolar range. PMID:21636894

The role of proline residues in the dynamics of transmembrane helices: the case of bacteriorhodopsin.

PubMed

Perálvarez-Marín, Alex; Bourdelande, José-Luis; Querol, Enric; Padrós, Esteve

2006-01-01

Proline residues in transmembrane helices have been found to have important roles in the functioning of membrane proteins. Moreover, Pro residues occur with high frequency in transmembrane alpha-helices, as compared to alpha-helices for soluble proteins. Here, we report several properties of the bacteriorhodopsin mutants P50A (helix B), P91A (helix C) and P186A (helix F). Compared to wild type, strongly perturbed behaviour has been found for these mutants. In the resting state, increased hydroxylamine accessibility and altered Asp-85 pKa and light-dark adaptation were observed. On light activation, hydroxylamine accessibility was increased and proton transport activity, M formation kinetics and FTIR difference spectra of M and N intermediates showed clear distortions. On the basis of these alterations and the near identity of the crystalline structures of mutants with that of wild type, we conclude that the transmembrane proline residues of bacteriorhodopsin fulfil a dynamic role in both the resting and the light-activated states. Our results are consistent with the notion that mutation of Pro to Ala allows the helix to increase its flexibility towards the direction originally hindered by the steric clash between the ring Cgamma and the carbonyl O of the i-4 residue, at the same time decreasing the mobility towards the opposite direction. Due to their properties, transmembrane Pro residues may serve as transmission elements of conformational changes during the transport process. We propose that these concepts can be extended to other transmembrane proteins.

Exploiting differences in caspase-2 and -3 S₂ subsites for selectivity: structure-based design, solid-phase synthesis and in vitro activity of novel substrate-based caspase-2 inhibitors.

PubMed

Maillard, Michel C; Brookfield, Frederick A; Courtney, Stephen M; Eustache, Florence M; Gemkow, Mark J; Handel, Rebecca K; Johnson, Laura C; Johnson, Peter D; Kerry, Mark A; Krieger, Florian; Meniconi, Mirco; Muñoz-Sanjuán, Ignacio; Palfrey, Jordan J; Park, Hyunsun; Schaertl, Sabine; Taylor, Malcolm G; Weddell, Derek; Dominguez, Celia

2011-10-01

Several caspases have been implicated in the pathogenesis of Huntington's disease (HD); however, existing caspase inhibitors lack the selectivity required to investigate the specific involvement of individual caspases in the neuronal cell death associated with HD. In order to explore the potential role played by caspase-2, the potent but non-selective canonical Ac-VDVAD-CHO caspase-2 inhibitor 1 was rationally modified at the P(2) residue in an attempt to decrease its activity against caspase-3. With the aid of structural information on the caspase-2, and -3 active sites and molecular modeling, a 3-(S)-substituted-l-proline along with four additional scaffold variants were selected as P(2) elements for their predicted ability to clash sterically with a residue of the caspase-3 S(2) pocket. These elements were then incorporated by solid-phase synthesis into pentapeptide aldehydes 33a-v. Proline-based compound 33h bearing a bulky 3-(S)-substituent displayed advantageous characteristics in biochemical and cellular assays with 20- to 60-fold increased selectivity for caspase-2 and ∼200-fold decreased caspase-3 potency compared to the reference inhibitor 1. Further optimization of this prototype compound may lead to the discovery of valuable pharmacological tools for the study of caspase-2 mediated cell death, particularly as it relates to HD. Copyright © 2011 Elsevier Ltd. All rights reserved.

Southeast Asia Report

DTIC Science & Technology

1987-03-25

Karya, directorate general, in the introduction of processing a system to keep water free of bacterias by benefiting the power of the sunshine. A...Kalinga-Apayao, Quirino, Quezon, Nueva Ecija, Albay, Mindoro Oriental, Aklan, Lanao del Norte and Davao. The biggest clash was in Mandog, Davao...Isabela. One insurgent was killed in a clash with NPA rebels in Kabugao, Kalinga-Apayao; and other casualties were in Quirino; Nueva Ecija; Sariyaya

In the Aftermath of War: Cultural Clashes of the Twenties. A Unit of Study for Grades 9-12.

ERIC Educational Resources Information Center

Gifford, Nina

This unit is a collection of lessons for teaching about cultural clashes. Based on primary sources, the unit contains teacher background materials and three lesson plans with student resources. These lessons deal with the United States between World War I and World War II. The United States emerged from World War I with seismic faults in its…

The Clash of Evaluations: In Search of the Missing Link between School Accountability and School Improvement--Experiences from Cyprus

ERIC Educational Resources Information Center

Brauckmann, Stefan; Pashiardis, Petros

2010-01-01

Purpose: The main purpose of this paper is to examine more closely the tension between, on the one hand, forms of internal school improvement based on internal evaluation measures and, on the other hand, control and legitimisation needs grounded on external evaluation measures. Design/methodology/approach: The clash of these forms of evaluation is…

Cultural Dimensions of Strategy and Policy

DTIC Science & Technology

2009-05-01

Amartya Sen has been one of the most vocal critics of the “Clash of Civilizations” theory. An economist who integrates economics with social action and...inevitable. Sen called for a more nuanced and sophisticated analysis that recognizes the immense diversity and plurality of identities while integrating...13th century. 19. Samuel Huntington, The Clash of Civilizations and the Remaking of the World Order, New York: Simon & Schuster, 1996. 20. Amartya

Initial laboratory experience with a novel ultrasound probe for standard and single-port robotic kidney surgery: increasing console surgeon autonomy and minimizing instrument clashing.

PubMed

Yakoubi, Rachid; Autorino, Riccardo; Laydner, Humberto; Guillotreau, Julien; White, Michael A; Hillyer, Shahab; Spana, Gregory; Khanna, Rakesh; Isaac, Wahib; Haber, Georges-Pascal; Stein, Robert J; Kaouk, Jihad H

2012-06-01

The aim of this study was to evaluate a novel ultrasound probe specifically developed for robotic surgery by determining its efficiency in identifying renal tumors. The study was carried out using the Da Vinci™ surgical system in one female pig. Renal tumor targets were created by percutaneous injection of a tumor mimic mixture. Single-port and standard robotic partial nephrectomy were performed. Intraoperative ultrasound was performed using both standard laparoscopic probe and the new ProART™ Robotic probe. Probe maneuverability and ease of handling for tumor localization were recorded. The standard laparoscopic probe was guided by the assistant. Significant clashing with robotic arms was noted during the single-port procedure. The novel robotic probe was easily introduced through the assistant trocar, and held by the console surgeon using the robotic Prograsp™ with no registered clashing in the external operative field. The average time for grasping the new robotic probe was less than 10 s. Once inserted and grasped, no limitation was found in terms of instrument clashing during the single-port procedure. This novel ultrasound probe developed for robotic surgery was noted to be user-friendly when performing porcine standard and especially single-port robotic partial nephrectomy. Copyright © 2011 John Wiley & Sons, Ltd.

Calibrating the Planck cluster mass scale with CLASH

NASA Astrophysics Data System (ADS)

Penna-Lima, M.; Bartlett, J. G.; Rozo, E.; Melin, J.-B.; Merten, J.; Evrard, A. E.; Postman, M.; Rykoff, E.

2017-08-01

We determine the mass scale of Planck galaxy clusters using gravitational lensing mass measurements from the Cluster Lensing And Supernova survey with Hubble (CLASH). We have compared the lensing masses to the Planck Sunyaev-Zeldovich (SZ) mass proxy for 21 clusters in common, employing a Bayesian analysis to simultaneously fit an idealized CLASH selection function and the distribution between the measured observables and true cluster mass. We used a tiered analysis strategy to explicitly demonstrate the importance of priors on weak lensing mass accuracy. In the case of an assumed constant bias, bSZ, between true cluster mass, M500, and the Planck mass proxy, MPL, our analysis constrains 1-bSZ = 0.73 ± 0.10 when moderate priors on weak lensing accuracy are used, including a zero-mean Gaussian with standard deviation of 8% to account for possible bias in lensing mass estimations. Our analysis explicitly accounts for possible selection bias effects in this calibration sourced by the CLASH selection function. Our constraint on the cluster mass scale is consistent with recent results from the Weighing the Giants program and the Canadian Cluster Comparison Project. It is also consistent, at 1.34σ, with the value needed to reconcile the Planck SZ cluster counts with Planck's base ΛCDM model fit to the primary cosmic microwave background anisotropies.

Mass-induced sea level variations in the Red Sea from steric-corrected altimetry, GRACE, in-situ bottom pressure records, and hydrographic observations

NASA Astrophysics Data System (ADS)

Feng, Wei; Lemoine, Jean-Michel; Zhong, Min; Xu, Houze

2014-05-01

An annual amplitude of ~18 cm mass-induced sea level variations (SLV) in the Red Sea is detected from steric-corrected altimetry and the Gravity Recovery and Climate Experiment (GRACE) satellites from 2003 to 2011, which dominates the mean sea level in the region. Seawater mass variations here generally reach maximum in late January/early February. The steric component of SLV calculated from oceanographic temperature and salinity data is relatively small and peaks about seven months later than mass variations. The phase difference between the steric SLV and the mass-induced SLV indicates that when the Red Sea gains the mass from inflow water in winter, the steric SLV fall, and vice versa in summer. In-situ bottom pressure records in the eastern coast of the Red Sea validate the high mass variability observed by steric-corrected altimetry and GRACE. Furthermore, we compare the horizontal water mass flux in the Red Sea from steric-corrected altimetry and GRACE with that estimated from hydrographic observations.

Poisson-Nernst-Planck equations with steric effects - non-convexity and multiple stationary solutions

NASA Astrophysics Data System (ADS)

Gavish, Nir

2018-04-01

We study the existence and stability of stationary solutions of Poisson-Nernst-Planck equations with steric effects (PNP-steric equations) with two counter-charged species. We show that within a range of parameters, steric effects give rise to multiple solutions of the corresponding stationary equation that are smooth. The PNP-steric equation, however, is found to be ill-posed at the parameter regime where multiple solutions arise. Following these findings, we introduce a novel PNP-Cahn-Hilliard model, show that it is well-posed and that it admits multiple stationary solutions that are smooth and stable. The various branches of stationary solutions and their stability are mapped utilizing bifurcation analysis and numerical continuation methods.

CLASH-X: A Comparison of Lensing and X-Ray Techniques for Measuring the Mass Profiles of Galaxy Clusters

NASA Astrophysics Data System (ADS)

Donahue, Megan; Voit, G. Mark; Mahdavi, Andisheh; Umetsu, Keiichi; Ettori, Stefano; Merten, Julian; Postman, Marc; Hoffer, Aaron; Baldi, Alessandro; Coe, Dan; Czakon, Nicole; Bartelmann, Mattias; Benitez, Narciso; Bouwens, Rychard; Bradley, Larry; Broadhurst, Tom; Ford, Holland; Gastaldello, Fabio; Grillo, Claudio; Infante, Leopoldo; Jouvel, Stephanie; Koekemoer, Anton; Kelson, Daniel; Lahav, Ofer; Lemze, Doron; Medezinski, Elinor; Melchior, Peter; Meneghetti, Massimo; Molino, Alberto; Moustakas, John; Moustakas, Leonidas A.; Nonino, Mario; Rosati, Piero; Sayers, Jack; Seitz, Stella; Van der Wel, Arjen; Zheng, Wei; Zitrin, Adi

2014-10-01

We present profiles of temperature, gas mass, and hydrostatic mass estimated from new and archival X-ray observations of CLASH clusters. We compare measurements derived from XMM and Chandra observations with one another and compare both to gravitational lensing mass profiles derived with CLASH Hubble Space Telescope and Subaru Telescope lensing data. Radial profiles of Chandra and XMM measurements of electron density and enclosed gas mass are nearly identical, indicating that differences in hydrostatic masses inferred from X-ray observations arise from differences in gas-temperature measurements. Encouragingly, gas temperatures measured in clusters by XMM and Chandra are consistent with one another at ~100-200 kpc radii, but XMM temperatures systematically decline relative to Chandra temperatures at larger radii. The angular dependence of the discrepancy suggests that additional investigation on systematics such as the XMM point-spread function correction, vignetting, and off-axis responses is yet required. We present the CLASH-X mass-profile comparisons in the form of cosmology-independent and redshift-independent circular-velocity profiles. We argue that comparisons of circular-velocity profiles are the most robust way to assess mass bias. Ratios of Chandra hydrostatic equilibrium (HSE) mass profiles to CLASH lensing profiles show no obvious radial dependence in the 0.3-0.8 Mpc range. However, the mean mass biases inferred from the weak-lensing (WL) and SaWLens data are different. As an example, the weighted-mean value at 0.5 Mpc is langbrang = 0.12 for the WL comparison and langbrang = -0.11 for the SaWLens comparison. The ratios of XMM HSE mass profiles to CLASH lensing profiles show a pronounced radial dependence in the 0.3-1.0 Mpc range, with a weighted mean mass bias value rising to langbrang >~ 0.3 at ~1 Mpc for the WL comparison and langbrang ≈ 0.25 for the SaWLens comparison. The enclosed gas mass profiles from both Chandra and XMM rise to a value ≈1/8 times the total-mass profiles inferred from lensing at ≈0.5 Mpc and remain constant outside of that radius, suggesting that M gas × 8 profiles may be an excellent proxy for total-mass profiles at >~ 0.5 Mpc in massive galaxy clusters.

CLASH-X: A comparison of lensing and X-ray techniques for measuring the mass profiles of galaxy clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donahue, Megan; Voit, G. Mark; Hoffer, Aaron

2014-10-20

We present profiles of temperature, gas mass, and hydrostatic mass estimated from new and archival X-ray observations of CLASH clusters. We compare measurements derived from XMM and Chandra observations with one another and compare both to gravitational lensing mass profiles derived with CLASH Hubble Space Telescope and Subaru Telescope lensing data. Radial profiles of Chandra and XMM measurements of electron density and enclosed gas mass are nearly identical, indicating that differences in hydrostatic masses inferred from X-ray observations arise from differences in gas-temperature measurements. Encouragingly, gas temperatures measured in clusters by XMM and Chandra are consistent with one another atmore » ∼100-200 kpc radii, but XMM temperatures systematically decline relative to Chandra temperatures at larger radii. The angular dependence of the discrepancy suggests that additional investigation on systematics such as the XMM point-spread function correction, vignetting, and off-axis responses is yet required. We present the CLASH-X mass-profile comparisons in the form of cosmology-independent and redshift-independent circular-velocity profiles. We argue that comparisons of circular-velocity profiles are the most robust way to assess mass bias. Ratios of Chandra hydrostatic equilibrium (HSE) mass profiles to CLASH lensing profiles show no obvious radial dependence in the 0.3-0.8 Mpc range. However, the mean mass biases inferred from the weak-lensing (WL) and SaWLens data are different. As an example, the weighted-mean value at 0.5 Mpc is (b) = 0.12 for the WL comparison and (b) = –0.11 for the SaWLens comparison. The ratios of XMM HSE mass profiles to CLASH lensing profiles show a pronounced radial dependence in the 0.3-1.0 Mpc range, with a weighted mean mass bias value rising to (b) ≳ 0.3 at ∼1 Mpc for the WL comparison and (b) ≈ 0.25 for the SaWLens comparison. The enclosed gas mass profiles from both Chandra and XMM rise to a value ≈1/8 times the total-mass profiles inferred from lensing at ≈0.5 Mpc and remain constant outside of that radius, suggesting that M {sub gas} × 8 profiles may be an excellent proxy for total-mass profiles at ≳ 0.5 Mpc in massive galaxy clusters.« less

The Morphologies and Alignments of Gas, Mass, and the Central Galaxies of CLASH Clusters of Galaxies

NASA Astrophysics Data System (ADS)

Donahue, Megan; Ettori, Stefano; Rasia, Elena; Sayers, Jack; Zitrin, Adi; Meneghetti, Massimo; Voit, G. Mark; Golwala, Sunil; Czakon, Nicole; Yepes, Gustavo; Baldi, Alessandro; Koekemoer, Anton; Postman, Marc

2016-03-01

Morphology is often used to infer the state of relaxation of galaxy clusters. The regularity, symmetry, and degree to which a cluster is centrally concentrated inform quantitative measures of cluster morphology. The Cluster Lensing and Supernova survey with Hubble Space Telescope (CLASH) used weak and strong lensing to measure the distribution of matter within a sample of 25 clusters, 20 of which were deemed to be “relaxed” based on their X-ray morphology and alignment of the X-ray emission with the Brightest Cluster Galaxy. Toward a quantitative characterization of this important sample of clusters, we present uniformly estimated X-ray morphological statistics for all 25 CLASH clusters. We compare X-ray morphologies of CLASH clusters with those identically measured for a large sample of simulated clusters from the MUSIC-2 simulations, selected by mass. We confirm a threshold in X-ray surface brightness concentration of C ≳ 0.4 for cool-core clusters, where C is the ratio of X-ray emission inside 100 h70-1 kpc compared to inside 500 {h}70-1 kpc. We report and compare morphologies of these clusters inferred from Sunyaev-Zeldovich Effect (SZE) maps of the hot gas and in from projected mass maps based on strong and weak lensing. We find a strong agreement in alignments of the orientation of major axes for the lensing, X-ray, and SZE maps of nearly all of the CLASH clusters at radii of 500 kpc (approximately 1/2 R500 for these clusters). We also find a striking alignment of clusters shapes at the 500 kpc scale, as measured with X-ray, SZE, and lensing, with that of the near-infrared stellar light at 10 kpc scales for the 20 “relaxed” clusters. This strong alignment indicates a powerful coupling between the cluster- and galaxy-scale galaxy formation processes.

Channel Gating Dependence on Pore Lining Helix Glycine Residues in Skeletal Muscle Ryanodine Receptor.

PubMed

Mei, Yingwu; Xu, Le; Mowrey, David D; Mendez Giraldez, Raul; Wang, Ying; Pasek, Daniel A; Dokholyan, Nikolay V; Meissner, Gerhard

2015-07-10

Type 1 ryanodine receptors (RyR1s) release Ca(2+) from the sarcoplasmic reticulum to initiate skeletal muscle contraction. The role of RyR1-G4934 and -G4941 in the pore-lining helix in channel gating and ion permeation was probed by replacing them with amino acid residues of increasing side chain volume. RyR1-G4934A, -G4941A, and -G4941V mutant channels exhibited a caffeine-induced Ca(2+) release response in HEK293 cells and bound the RyR-specific ligand [(3)H]ryanodine. In single channel recordings, significant differences in the number of channel events and mean open and close times were observed between WT and RyR1-G4934A and -G4941A. RyR1-G4934A had reduced K(+) conductance and ion selectivity compared with WT. Mutations further increasing the side chain volume at these positions (G4934V and G4941I) resulted in reduced caffeine-induced Ca(2+) release in HEK293 cells, low [(3)H]ryanodine binding levels, and channels that were not regulated by Ca(2+) and did not conduct Ca(2+) in single channel measurements. Computational predictions of the thermodynamic impact of mutations on protein stability indicated that although the G4934A mutation was tolerated, the G4934V mutation decreased protein stability by introducing clashes with neighboring amino acid residues. In similar fashion, the G4941A mutation did not introduce clashes, whereas the G4941I mutation resulted in intersubunit clashes among the mutated isoleucines. Co-expression of RyR1-WT with RyR1-G4934V or -G4941I partially restored the WT phenotype, which suggested lessening of amino acid clashes in heterotetrameric channel complexes. The results indicate that both glycines are important for RyR1 channel function by providing flexibility and minimizing amino acid clashes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

From information theory to quantitative description of steric effects.

PubMed

Alipour, Mojtaba; Safari, Zahra

2016-07-21

Immense efforts have been made in the literature to apply the information theory descriptors for investigating the electronic structure theory of various systems. In the present study, the information theoretic quantities, such as Fisher information, Shannon entropy, Onicescu information energy, and Ghosh-Berkowitz-Parr entropy, have been used to present a quantitative description for one of the most widely used concepts in chemistry, namely the steric effects. Taking the experimental steric scales for the different compounds as benchmark sets, there are reasonable linear relationships between the experimental scales of the steric effects and theoretical values of steric energies calculated from information theory functionals. Perusing the results obtained from the information theoretic quantities with the two representations of electron density and shape function, the Shannon entropy has the best performance for the purpose. On the one hand, the usefulness of considering the contributions of functional groups steric energies and geometries, and on the other hand, dissecting the effects of both global and local information measures simultaneously have also been explored. Furthermore, the utility of the information functionals for the description of steric effects in several chemical transformations, such as electrophilic and nucleophilic reactions and host-guest chemistry, has been analyzed. The functionals of information theory correlate remarkably with the stability of systems and experimental scales. Overall, these findings show that the information theoretic quantities can be introduced as quantitative measures of steric effects and provide further evidences of the quality of information theory toward helping theoreticians and experimentalists to interpret different problems in real systems.

Molecular dynamics investigations of BioH protein substrate specificity for biotin synthesis.

PubMed

Xue, Qiao; Cui, Ying-Lu; Zheng, Qing-Chuan; Zhang, Hong-Xing

2016-05-01

BioH, an enzyme of biotin synthesis, plays an important role in fatty acid synthesis which assembles the pimelate moiety. Pimeloyl-acyl carrier protein (ACP) methyl ester, which is long known to be a biotin precursor, is the physiological substrate of BioH. Azelayl methyl ester, which has a longer chain than pimeloyl methyl ester, conjugated to ACP is also indeed accepted by BioH with very low rate of hydrolysis. To date, the substrate specificity for BioH and the molecular origin for the experimentally observed rate changes of hydrolysis by the chain elongation have remained elusive. To this end, we have investigated chain elongation effects on the structures by using the fully atomistic molecular dynamics simulations combined with binding free energy calculations. The results indicate that the substrate specificity is determined by BioH together with ACP. The added two methylenes would increase the structural flexibility by protein motions at the interface of ACP and BioH, instead of making steric clashes with the side chains of the BioH hydrophobic cavity. On the other hand, the slower hydrolysis of azelayl substrate is suggested to be associated with the loose of contacts between BioH and ACP, and with the lost electrostatic interactions of two ionic/hydrogen bonding networks at the interface of the two proteins. The present study provides important insights into the structure-function relationships of the complex of BioH with pimeloyl-ACP methyl ester, which could contribute to further understanding about the mechanism of the biotin synthetic pathway, including the catalytic role of BioH.

I-TASSER: fully automated protein structure prediction in CASP8.

PubMed

Zhang, Yang

2009-01-01

The I-TASSER algorithm for 3D protein structure prediction was tested in CASP8, with the procedure fully automated in both the Server and Human sections. The quality of the server models is close to that of human ones but the human predictions incorporate more diverse templates from other servers which improve the human predictions in some of the distant homology targets. For the first time, the sequence-based contact predictions from machine learning techniques are found helpful for both template-based modeling (TBM) and template-free modeling (FM). In TBM, although the accuracy of the sequence based contact predictions is on average lower than that from template-based ones, the novel contacts in the sequence-based predictions, which are complementary to the threading templates in the weakly or unaligned regions, are important to improve the global and local packing in these regions. Moreover, the newly developed atomic structural refinement algorithm was tested in CASP8 and found to improve the hydrogen-bonding networks and the overall TM-score, which is mainly due to its ability of removing steric clashes so that the models can be generated from cluster centroids. Nevertheless, one of the major issues of the I-TASSER pipeline is the model selection where the best models could not be appropriately recognized when the correct templates are detected only by the minority of the threading algorithms. There are also problems related with domain-splitting and mirror image recognition which mainly influences the performance of I-TASSER modeling in the FM-based structure predictions. Copyright 2009 Wiley-Liss, Inc.

Undergraduates improve upon published crystal structure in class assignment.

PubMed

Horowitz, Scott; Koldewey, Philipp; Bardwell, James C

2014-01-01

Recently, 57 undergraduate students at the University of Michigan were assigned the task of solving a crystal structure, given only the electron density map of a 1.3 Å crystal structure from the electron density server, and the position of the N-terminal amino acid. To test their knowledge of amino acid chemistry, the students were not given the protein sequence. With minimal direction from the instructor on how the students should complete the assignment, the students fared remarkably well in this task, with over half the class able to reconstruct the original sequence with over 77% sequence identity, and with structures whose median ranked in the 91(st) percentile of all structures of comparable resolution in terms of structure quality. Fourteen percent of the students' structures produced Molprobity steric clash validation scores even better than that of the original structure, suggesting that multiple students achieved an improvement in the overall structure quality compared to the published structure. Students were able to delineate limiting case chemical environments, such as charged interactions or complete solvent exposure, but were less able to distinguish finer details of hydrogen bonding or hydrophobicity. Our results prompt several questions: why were students able to perform so well in their structural validation scores? How were some students able to outperform the 88% sequence identity mark that would constitute a perfect score, given the level of degenerate density or surface residues with poor density? And how can the methodology used by the best students inform the practices of professional X-ray crystallographers? Copyright © 2014 Wiley Periodicals, Inc.

Crystal structure of calpain-3 penta-EF-hand (PEF) domain - a homodimerized PEF family member with calcium bound at the fifth EF-hand

DOE Office of Scientific and Technical Information (OSTI.GOV)

Partha, Sarathy K.; Ravulapalli, Ravikiran; Allingham, John S.

2014-08-21

Calpains are Ca 2+dependent intracellular cysteine proteases that cleave a wide range of protein substrates to help implement Ca 2+ signaling in the cell. The major isoforms of this enzyme family, calpain-1 and calpain-2, are heterodimers of a large and a small subunit, with the main dimer interface being formed through their C-terminal penta-EF hand (PEF) domains. Calpain-3, or p94, is a skeletal muscle-specific isoform that is genetically linked to limb-girdle muscular dystrophy. Biophysical and modeling studies with the PEF domain of calpain-3 support the suggestion that full-length calpain-3 exists as a homodimer. Here, we report the crystallization of calpain-3'smore » PEF domain and its crystal structure in the presence of Ca 2+, which provides evidence for the homodimer architecture of calpain-3 and supports the molecular model that places a protease core at either end of the elongated dimer. Unlike other calpain PEF domain structures, the calpain-3 PEF domain contains a Ca 2+ bound at the EF5-hand used for homodimer association. Three of the four Ca 2+-binding EF-hands of the PEF domains are concentrated near the protease core, and have the potential to radically change the local charge within the dimer during Ca 2+ signaling. Examination of the homodimer interface shows that there would be steric clashes if the calpain-3 large subunit were to try to pair with a calpain small subunit.« less

Cul3-mediated Nrf2 ubiquitination and antioxidant response element (ARE) activation are dependent on the partial molar volume at position 151 of Keap1.

PubMed

Eggler, Aimee L; Small, Evan; Hannink, Mark; Mesecar, Andrew D

2009-07-29

Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that activates transcription of a battery of cytoprotective genes by binding to the ARE (antioxidant response element). Nrf2 is repressed by the cysteine-rich Keap1 (kelch-like ECH-associated protein 1) protein, which targets Nrf2 for ubiquitination and subsequent degradation by a Cul3 (cullin 3)-mediated ubiquitination complex. We find that modification of Cys(151) of human Keap1, by mutation to a tryptophan, relieves the repression by Keap1 and allows activation of the ARE by Nrf2. The Keap1 C151W substitution has a decreased affinity for Cul3, and can no longer serve to target Nrf2 for ubiquitination, though it retains its affinity for Nrf2. A series of 12 mutant Keap1 proteins, each containing a different residue at position 151, was constructed to explore the chemistry required for this effect. The series reveals that the extent to which Keap1 loses the ability to target Nrf2 for degradation, and hence the ability to repress ARE activation, correlates well with the partial molar volume of the residue. Other physico-chemical properties do not appear to contribute significantly to the effect. Based on this finding, a structural model is proposed whereby large residues at position 151 cause steric clashes that lead to alteration of the Keap1-Cul3 interaction. This model has significant implications for how electrophiles which modify Cys(151), disrupt the repressive function of Keap1.

A normal mode-based geometric simulation approach for exploring biologically relevant conformational transitions in proteins.

PubMed

Ahmed, Aqeel; Rippmann, Friedrich; Barnickel, Gerhard; Gohlke, Holger

2011-07-25

A three-step approach for multiscale modeling of protein conformational changes is presented that incorporates information about preferred directions of protein motions into a geometric simulation algorithm. The first two steps are based on a rigid cluster normal-mode analysis (RCNMA). Low-frequency normal modes are used in the third step (NMSim) to extend the recently introduced idea of constrained geometric simulations of diffusive motions in proteins by biasing backbone motions of the protein, whereas side-chain motions are biased toward favorable rotamer states. The generated structures are iteratively corrected regarding steric clashes and stereochemical constraint violations. The approach allows performing three simulation types: unbiased exploration of conformational space; pathway generation by a targeted simulation; and radius of gyration-guided simulation. When applied to a data set of proteins with experimentally observed conformational changes, conformational variabilities are reproduced very well for 4 out of 5 proteins that show domain motions, with correlation coefficients r > 0.70 and as high as r = 0.92 in the case of adenylate kinase. In 7 out of 8 cases, NMSim simulations starting from unbound structures are able to sample conformations that are similar (root-mean-square deviation = 1.0-3.1 Å) to ligand bound conformations. An NMSim generated pathway of conformational change of adenylate kinase correctly describes the sequence of domain closing. The NMSim approach is a computationally efficient alternative to molecular dynamics simulations for conformational sampling of proteins. The generated conformations and pathways of conformational transitions can serve as input to docking approaches or as starting points for more sophisticated sampling techniques.

The Projection Analysis of NMR Chemical Shifts Reveals Extended EPAC Autoinhibition Determinants

PubMed Central

Selvaratnam, Rajeevan; VanSchouwen, Bryan; Fogolari, Federico; Mazhab-Jafari, Mohammad T.; Das, Rahul; Melacini, Giuseppe

2012-01-01

EPAC is a cAMP-dependent guanine nucleotide exchange factor that serves as a prototypical molecular switch for the regulation of essential cellular processes. Although EPAC activation by cAMP has been extensively investigated, the mechanism of EPAC autoinhibition is still not fully understood. The steric clash between the side chains of two conserved residues, L273 and F300 in EPAC1, has been previously shown to oppose the inactive-to-active conformational transition in the absence of cAMP. However, it has also been hypothesized that autoinhibition is assisted by entropic losses caused by quenching of dynamics that occurs if the inactive-to-active transition takes place in the absence of cAMP. Here, we test this hypothesis through the comparative NMR analysis of several EPAC1 mutants that target different allosteric sites of the cAMP-binding domain (CBD). Using what to our knowledge is a novel projection analysis of NMR chemical shifts to probe the effect of the mutations on the autoinhibition equilibrium of the CBD, we find that whenever the apo/active state is stabilized relative to the apo/inactive state, dynamics are consistently quenched in a conserved loop (β2-β3) and helix (α5) of the CBD. Overall, our results point to the presence of conserved and nondegenerate determinants of CBD autoinhibition that extends beyond the originally proposed L273/F300 residue pair, suggesting that complete activation necessitates the simultaneous suppression of multiple autoinhibitory mechanisms, which in turn confers added specificity for the cAMP allosteric effector. PMID:22325287

Template-based protein-protein docking exploiting pairwise interfacial residue restraints.

PubMed

Xue, Li C; Rodrigues, João P G L M; Dobbs, Drena; Honavar, Vasant; Bonvin, Alexandre M J J

2017-05-01

Although many advanced and sophisticated ab initio approaches for modeling protein-protein complexes have been proposed in past decades, template-based modeling (TBM) remains the most accurate and widely used approach, given a reliable template is available. However, there are many different ways to exploit template information in the modeling process. Here, we systematically evaluate and benchmark a TBM method that uses conserved interfacial residue pairs as docking distance restraints [referred to as alpha carbon-alpha carbon (CA-CA)-guided docking]. We compare it with two other template-based protein-protein modeling approaches, including a conserved non-pairwise interfacial residue restrained docking approach [referred to as the ambiguous interaction restraint (AIR)-guided docking] and a simple superposition-based modeling approach. Our results show that, for most cases, the CA-CA-guided docking method outperforms both superposition with refinement and the AIR-guided docking method. We emphasize the superiority of the CA-CA-guided docking on cases with medium to large conformational changes, and interactions mediated through loops, tails or disordered regions. Our results also underscore the importance of a proper refinement of superimposition models to reduce steric clashes. In summary, we provide a benchmarked TBM protocol that uses conserved pairwise interface distance as restraints in generating realistic 3D protein-protein interaction models, when reliable templates are available. The described CA-CA-guided docking protocol is based on the HADDOCK platform, which allows users to incorporate additional prior knowledge of the target system to further improve the quality of the resulting models. © The Author 2016. Published by Oxford University Press.

Use of steric encumbrance to develop conjugated nanoporous polymers for metal-free catalytic hydrogenation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Chengcheng; Zhu, Xiang; Abney, Carter W.

The design and synthesis of metal-free heterogeneous catalysts for efficient hydrogenation remains a great challenge. Here we report a novel approach to create conjugated nanoporous polymers with efficient hydrogenation activities toward unsaturated ketones by leveraging the innate steric encumbrance. The steric bulk of the framework as well as the local sterics of the Lewis basic sites within the polymeric skeleton result in the generation of the putative catalyst. This approach opens up new possibilities for the development of innovative metal-free heterogeneous catalysts.

Use of steric encumbrance to develop conjugated nanoporous polymers for metal-free catalytic hydrogenation

DOE PAGES

Tian, Chengcheng; Zhu, Xiang; Abney, Carter W.; ...

2016-09-08

The design and synthesis of metal-free heterogeneous catalysts for efficient hydrogenation remains a great challenge. Here we report a novel approach to create conjugated nanoporous polymers with efficient hydrogenation activities toward unsaturated ketones by leveraging the innate steric encumbrance. The steric bulk of the framework as well as the local sterics of the Lewis basic sites within the polymeric skeleton result in the generation of the putative catalyst. Lastly, this approach opens up new possibilities for the development of innovative metal-free heterogeneous catalysts.

Use of steric encumbrance to develop conjugated nanoporous polymers for metal-free catalytic hydrogenation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Chengcheng; Zhu, Xiang; Abney, Carter W.

The design and synthesis of metal-free heterogeneous catalysts for efficient hydrogenation remains a great challenge. Here we report a novel approach to create conjugated nanoporous polymers with efficient hydrogenation activities toward unsaturated ketones by leveraging the innate steric encumbrance. The steric bulk of the framework as well as the local sterics of the Lewis basic sites within the polymeric skeleton result in the generation of the putative catalyst. Lastly, this approach opens up new possibilities for the development of innovative metal-free heterogeneous catalysts.

Creating creationists: The influence of 'issues framing' on our understanding of public perceptions of clash narratives between evolutionary science and belief.

PubMed

Elsdon-Baker, Fern

2015-05-01

Clash narratives relating to evolutionary science and personal belief are a recurrent theme in media or public space discourse. However, a 2009 British Council poll undertaken in 10 countries worldwide shows that the perception of a necessary clash between evolutionary worldviews and belief in a God is a minority viewpoint. How then does the popular conception that there is an ongoing conflict between evolution and belief in God arise? One contributing factor is the framing and categorization of creationism and evolutionism within large-scale surveys for use within media campaigns. This article examines the issue framing within four polls conducted in the United Kingdom and internationally between 2008 and 2013. It argues that by ignoring the complexity and range of perspectives individuals hold, or by framing evolutionary science as atheistic, we are potentially creating 'creationists' - including 'Islamic creationists' - both figuratively and literally. © The Author(s) 2015.

Mapping the miRNA interactome by crosslinking ligation and sequencing of hybrids (CLASH)

PubMed Central

Helwak, Aleksandra; Tollervey, David

2014-01-01

RNA-RNA interactions play critical roles in many cellular processes but studying them is difficult and laborious. Here, we describe an experimental procedure, termed crosslinking ligation and sequencing of hybrids (CLASH), which allows high-throughput identification of sites of RNA-RNA interaction. During CLASH, a tagged bait protein is UV crosslinked in vivo to stabilise RNA interactions and purified under denaturing conditions. RNAs associated with the bait protein are partially truncated, and the ends of RNA-duplexes are ligated together. Following linker addition, cDNA library preparation and high-throughput sequencing, the ligated duplexes give rise to chimeric cDNAs, which unambiguously identify RNA-RNA interaction sites independent of bioinformatic predictions. This protocol is optimized for studying miRNA targets bound by Argonaute proteins, but should be easily adapted for other RNA-binding proteins and classes of RNA. The protocol requires around 5 days to complete, excluding the time required for high-throughput sequencing and bioinformatic analyses. PMID:24577361

Comparing Dark Energy Survey and HST –CLASH observations of the galaxy cluster RXC J2248.7-4431: implications for stellar mass versus dark matter

DOE PAGES

Palmese, A.; Lahav, O.; Banerji, M.; ...

2016-08-20

We derive the stellar mass fraction in the galaxy cluster RXC J2248.7-4431 observed with the Dark Energy Survey (DES) during the Science Verification period. We compare the stellar mass results from DES (5 filters) with those from the Hubble Space Telescope CLASH (17 filters). When the cluster spectroscopic redshift is assumed, we show that stellar masses from DES can be estimated within 25% of CLASH values. We compute the stellar mass contribution coming from red and blue galaxies, and study the relation between stellar mass and the underlying dark matter using weak lensing studies with DES and CLASH. An analysismore » of the radial profiles of the DES total and stellar mass yields a stellar-to-total fraction of f*=7.0+-2.2x10^-3 within a radius of r_200c~3 Mpc. Our analysis also includes a comparison of photometric redshifts and star/galaxy separation efficiency for both datasets. We conclude that space-based small field imaging can be used to calibrate the galaxy properties in DES for the much wider field of view. The technique developed to derive the stellar mass fraction in galaxy clusters can be applied to the ~100 000 clusters that will be observed within this survey. The stacking of all the DES clusters would reduce the errors on f* estimates and deduce important information about galaxy evolution.« less

Comparing Dark Energy Survey and HST-CLASH observations of the galaxy cluster RXC J2248.7-4431: implications for stellar mass versus dark matter

NASA Astrophysics Data System (ADS)

Palmese, A.; Lahav, O.; Banerji, M.; Gruen, D.; Jouvel, S.; Melchior, P.; Aleksić, J.; Annis, J.; Diehl, H. T.; Hartley, W. G.; Jeltema, T.; Romer, A. K.; Rozo, E.; Rykoff, E. S.; Seitz, S.; Suchyta, E.; Zhang, Y.; Abbott, T. M. C.; Abdalla, F. B.; Allam, S.; Benoit-Lévy, A.; Bertin, E.; Brooks, D.; Buckley-Geer, E.; Burke, D. L.; Capozzi, D.; Carnero Rosell, A.; Carrasco Kind, M.; Carretero, J.; Crocce, M.; Cunha, C. E.; D'Andrea, C. B.; da Costa, L. N.; Desai, S.; Dietrich, J. P.; Doel, P.; Estrada, J.; Evrard, A. E.; Flaugher, B.; Frieman, J.; Gerdes, D. W.; Goldstein, D. A.; Gruendl, R. A.; Gutierrez, G.; Honscheid, K.; James, D. J.; Kuehn, K.; Kuropatkin, N.; Li, T. S.; Lima, M.; Maia, M. A. G.; Marshall, J. L.; Miller, C. J.; Miquel, R.; Nord, B.; Ogando, R.; Plazas, A. A.; Roodman, A.; Sanchez, E.; Scarpine, V.; Sevilla-Noarbe, I.; Smith, R. C.; Soares-Santos, M.; Sobreira, F.; Swanson, M. E. C.; Tarle, G.; Thomas, D.; Tucker, D.; Vikram, V.

2016-12-01

We derive the stellar mass fraction in the galaxy cluster RXC J2248.7-4431 observed with the Dark Energy Survey (DES) during the Science Verification period. We compare the stellar mass results from DES (five filters) with those from the Hubble Space Telescope Cluster Lensing And Supernova Survey (CLASH; 17 filters). When the cluster spectroscopic redshift is assumed, we show that stellar masses from DES can be estimated within 25 per cent of CLASH values. We compute the stellar mass contribution coming from red and blue galaxies, and study the relation between stellar mass and the underlying dark matter using weak lensing studies with DES and CLASH. An analysis of the radial profiles of the DES total and stellar mass yields a stellar-to-total fraction of f⋆ = (6.8 ± 1.7) × 10-3 within a radius of r200c ≃ 2 Mpc. Our analysis also includes a comparison of photometric redshifts and star/galaxy separation efficiency for both data sets. We conclude that space-based small field imaging can be used to calibrate the galaxy properties in DES for the much wider field of view. The technique developed to derive the stellar mass fraction in galaxy clusters can be applied to the ˜100 000 clusters that will be observed within this survey and yield important information about galaxy evolution.

Aggression and violence around the world: A model of CLimate, Aggression, and Self-control in Humans (CLASH).

PubMed

Van Lange, Paul A M; Rinderu, Maria I; Bushman, Brad J

2017-01-01

Worldwide there are substantial differences within and between countries in aggression and violence. Although there are various exceptions, a general rule is that aggression and violence increase as one moves closer to the equator, which suggests the important role of climate differences. While this pattern is robust, theoretical explanations for these large differences in aggression and violence within countries and around the world are lacking. Most extant explanations focus on the influence of average temperature as a factor that triggers aggression (The General Aggression Model), or the notion that warm temperature allows for more social interaction situations (Routine Activity Theory) in which aggression is likely to unfold. We propose a new model, CLimate, Aggression, and Self-control in Humans (CLASH), that helps us to understand differences within and between countries in aggression and violence in terms of differences in climate. Lower temperatures, and especially larger degrees of seasonal variation in climate, call for individuals and groups to adopt a slower life history strategy, a greater focus on the future (vs. present), and a stronger focus on self-control. The CLASH model further outlines that slow life strategy, future orientation, and strong self-control are important determinants of inhibiting aggression and violence. We also discuss how CLASH differs from other recently developed models that emphasize climate differences for understanding conflict. We conclude by discussing the theoretical and societal importance of climate in shaping individual and societal differences in aggression and violence.

Comparing Dark Energy Survey and HST –CLASH observations of the galaxy cluster RXC J2248.7-4431: implications for stellar mass versus dark matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palmese, A.; Lahav, O.; Banerji, M.

We derive the stellar mass fraction in the galaxy cluster RXC J2248.7-4431 observed with the Dark Energy Survey (DES) during the Science Verification period. We compare the stellar mass results from DES (5 filters) with those from the Hubble Space Telescope CLASH (17 filters). When the cluster spectroscopic redshift is assumed, we show that stellar masses from DES can be estimated within 25% of CLASH values. We compute the stellar mass contribution coming from red and blue galaxies, and study the relation between stellar mass and the underlying dark matter using weak lensing studies with DES and CLASH. An analysismore » of the radial profiles of the DES total and stellar mass yields a stellar-to-total fraction of f*=7.0+-2.2x10^-3 within a radius of r_200c~3 Mpc. Our analysis also includes a comparison of photometric redshifts and star/galaxy separation efficiency for both datasets. We conclude that space-based small field imaging can be used to calibrate the galaxy properties in DES for the much wider field of view. The technique developed to derive the stellar mass fraction in galaxy clusters can be applied to the ~100 000 clusters that will be observed within this survey. The stacking of all the DES clusters would reduce the errors on f* estimates and deduce important information about galaxy evolution.« less

Comparing Dark Energy Survey and HST –CLASH observations of the galaxy cluster RXC J2248.7-4431: implications for stellar mass versus dark matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palmese, A.; Lahav, O.; Banerji, M.

We derive the stellar mass fraction in the galaxy cluster RXC J2248.7-4431 observed with the Dark Energy Survey (DES) during the Science Verification period. We compare the stellar mass results from DES (five filters) with those from the Hubble Space Telescope Cluster Lensing And Supernova Survey (CLASH; 17 filters). When the cluster spectroscopic redshift is assumed, we show that stellar masses from DES can be estimated within 25 per cent of CLASH values. We compute the stellar mass contribution coming from red and blue galaxies, and study the relation between stellar mass and the underlying dark matter using weak lensingmore » studies with DES and CLASH. An analysis of the radial profiles of the DES total and stellar mass yields a stellar-to-total fraction of f(star) = (6.8 +/- 1.7) x 10(-3) within a radius of r(200c) similar or equal to 2 Mpc. Our analysis also includes a comparison of photometric redshifts and star/galaxy separation efficiency for both data sets. We conclude that space-based small field imaging can be used to calibrate the galaxy properties in DES for the much wider field of view. The technique developed to derive the stellar mass fraction in galaxy clusters can be applied to the similar to 100 000 clusters that will be observed within this survey and yield important information about galaxy evolution.« less

Precise strong lensing mass profile of the CLASH galaxy cluster MACS 2129

NASA Astrophysics Data System (ADS)

Monna, A.; Seitz, S.; Balestra, I.; Rosati, P.; Grillo, C.; Halkola, A.; Suyu, S. H.; Coe, D.; Caminha, G. B.; Frye, B.; Koekemoer, A.; Mercurio, A.; Nonino, M.; Postman, M.; Zitrin, A.

2017-04-01

We present a detailed strong lensing (SL) mass reconstruction of the core of the galaxy cluster MACS J2129.4-0741 (zcl = 0.589) obtained by combining high-resolution Hubble Space Telescope photometry from the CLASH (Cluster Lensing And Supernovae survey with Hubble) survey with new spectroscopic observations from the CLASH-VLT (Very Large Telescope) survey. A background bright red passive galaxy at zsp = 1.36, sextuply lensed in the cluster core, has four radial lensed images located over the three central cluster members. Further 19 background lensed galaxies are spectroscopically confirmed by our VLT survey, including 3 additional multiple systems. A total of 31 multiple images are used in the lensing analysis. This allows us to trace with high precision the total mass profile of the cluster in its very inner region (R < 100 kpc). Our final lensing mass model reproduces the multiple images systems identified in the cluster core with high accuracy of 0.4 arcsec. This translates to a high-precision mass reconstruction of MACS 2129, which is constrained at a level of 2 per cent. The cluster has Einstein parameter ΘE = (29 ± 4) arcsec and a projected total mass of Mtot(<ΘE) = (1.35 ± 0.03) × 1014 M⊙ within such radius. Together with the cluster mass profile, we provide here also the complete spectroscopic data set for the cluster members and lensed images measured with VLT/Visible Multi-Object Spectrograph within the CLASH-VLT survey.

Mass-induced sea level variations in the Red Sea from GRACE, steric-corrected altimetry, in situ bottom pressure records, and hydrographic observations

NASA Astrophysics Data System (ADS)

Feng, W.; Lemoine, J.-M.; Zhong, M.; Hsu, H. T.

2014-08-01

An annual amplitude of ∼18 cm mass-induced sea level variations (SLV) in the Red Sea is detected from the Gravity Recovery and Climate Experiment (GRACE) satellites and steric-corrected altimetry from 2003 to 2011. The annual mass variations in the region dominate the mean SLV, and generally reach maximum in late January/early February. The annual steric component of the mean SLV is relatively small (<3 cm) and out of phase of the mass-induced SLV. In situ bottom pressure records at the eastern coast of the Red Sea validate the high mass variability observed by steric-corrected altimetry and GRACE. In addition, the horizontal water mass flux of the Red Sea estimated from GRACE and steric-corrected altimetry is validated by hydrographic observations.

Discovery and Characterization of Gravitationally Lensed X-ray Sources in the CLASH Sample

NASA Astrophysics Data System (ADS)

Pasha, Imad; Van Weeren, Reinout J.; Santos, Felipe A.

2017-01-01

We present the discovery of ~20 gravitationally lensed X-ray sources in the Cluster Lensing And Supernova survey with Hubble (CLASH) survey, a sample of massive clusters of galaxies between z ~ 0.2-0.9 observed with the Hubble Space Telescope (HST). By combining CLASH imaging with Chandra X-ray Observatory observations of the same clusters, we select those sources in the HST images which are gravitationally lensed X-ray sources behind the clusters. Of those discovered sources, we determine various properties including source redshifts and magnifications, as well as performing X-ray spectral fits to determine source fluxes and luminosities. Prior to this study, only four lensed X-ray sources behind clusters have been found, thus to the best of our knowledge, our program is the first to systematically categorize lensed X-ray sources behind galaxy clusters.This work was supported by the SAO REU program, which is funded in part by the National Science Foundation REU and Department of Defense ASSURE programs under NSF Grant no. 1262851, and by the Smithsonian Institution.

Transnitrilation from Dimethylmalononitrile to Aryl Grignard and Lithium Reagents: A Practical Method for Aryl Nitrile Synthesis.

PubMed

Reeves, Jonathan T; Malapit, Christian A; Buono, Frederic G; Sidhu, Kanwar P; Marsini, Maurice A; Sader, C Avery; Fandrick, Keith R; Busacca, Carl A; Senanayake, Chris H

2015-07-29

An electrophilic cyanation of aryl Grignard or lithium reagents, generated in situ from the corresponding aryl bromides or iodides, by a transnitrilation with dimethylmalononitrile (DMMN) was developed. DMMN is a commercially available, bench-stable solid. The transnitrilation with DMMN avoids the use of toxic reagents and transition metals and occurs under mild reaction conditions, even for extremely sterically hindered substrates. The transnitrilation of aryllithium species generated by directed ortho-lithiation enabled a net C-H cyanation. The intermediacy of a Thorpe-type imine adduct in the reaction was supported by isolation of the corresponding ketone from the quenched reaction. Computational studies supported the energetic favorability of retro-Thorpe fragmentation of the imine adduct.

Crystal structures and intermolecular interactions of two novel antioxidant triazolyl-benzimidazole compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karayel, A., E-mail: matchlessjimmy@163.com, E-mail: yccaoh@hotmail.com; Özbey, S.; Ayhan-Kılcıgil, G.

2015-12-15

The crystal structures of 5-(2-(p-chlorophenylbenzimidazol-1-yl-methyl)-4-(3-fluorophenyl)-2, 4-dihydro-[1,2,4]-triazole-3-thione (G6C) and 5-(2-(p-chlorophenylbenzimidazol-1-yl-methyl)-4-(2-methylphenyl)-2, 4-dihydro-[1,2,4]-triazole-3-thione (G4C) have been determined by single-crystal X-ray diffraction. Benzimidazole ring systems in both molecules are planar. The triazole part is almost perpendicular to the phenyl and the benzimidazole parts of the molecules in order to avoid steric interactions between the rings. The crystal structures are stabilized by intermolecular hydrogen bonds between the amino group of the triazole and the nitrogen atom of benzimidazole of a neighboring molecule.

Study on steric transition in asymmetrical flow field-flow fractionation and application to characterization of high-energy material.

PubMed

Dou, Haiyang; Lee, Yong-Ju; Jung, Euo Chang; Lee, Byung-Chul; Lee, Seungho

2013-08-23

In field-flow fractionation (FFF), there is the 'steric transition' phenomenon where the sample elution mode changes from the normal to steric/hyperlayer mode. Accurate analysis by FFF requires understanding of the steric transition phenomenon, particularly when the sample has a broad size distribution, for which the effect by combination of different modes may become complicated to interpret. In this study, the steric transition phenomenon in asymmetrical flow FFF (AF4) was studied using polystyrene (PS) latex beads. The retention ratio (R) gradually decreases as the particle size increases (normal mode) and reaches a minimum (Ri) at diameter around 0.5μm, after which R increases with increasing diameter (steric/hyperlayer mode). It was found that the size-based selectivity (Sd) tends to increase as the channel thickness (w) increases. The retention behavior of cyclo-1,3,5-trimethylene-2,4,6-trinitramine (commonly called 'research department explosive' (RDX)) particles in AF4 was investigated by varying experimental parameters including w and flow rates. AF4 showed a good reproducibility in size determination of RDX particles with the relative standard deviation of 4.1%. The reliability of separation obtained by AF4 was evaluated by transmission electron microscopy (TEM). Copyright © 2013 Elsevier B.V. All rights reserved.

Orthogonal sampling in free-energy calculations of residue mutations in a tripeptide: TI versus λ-LEUS.

PubMed

Bieler, Noah S; Hünenberger, Philippe H

2015-08-15

In a recent article (Bieler et al., J. Chem. Theory Comput. 2014, 10, 3006), we introduced a combination of λ-dynamics and local-elevation umbrella-sampling termed λ-LEUS to calculate free-energy changes associated with alchemical processes using molecular dynamics simulations. This method was suggested to be more efficient than thermodynamic integration (TI), because the dynamical variation of the alchemical variable λ opens up pathways to circumvent barriers in the orthogonal space (defined by the N - 1 degrees of freedom that are not subjected to the sampling enhancement), a feature λ-LEUS shares with Hamiltonian replica-exchange (HR) approaches. However, the mutation considered, hydroquinone to benzene in water, was no real challenge in terms of orthogonal-space properties, which were restricted to solvent-relaxation processes. In the present article, we revisit the comparison between TI and λ-LEUS considering non-trivial mutations of the central residue X of a KXK tripeptide in water (with X = G, E, K, S, F, or Y). Side-chain interactions that may include salt bridges, hydrogen bonds or steric clashes lead to slow relaxation in the orthogonal space, mainly in the two-dimensional subspace spanned by the central φ and ψ dihedral angles of the peptide. The efficiency enhancement afforded by λ-LEUS is confirmed in this more complex test system and can be attributed explicitly to the improved sampling of the orthogonal space. The sensitivity of the results to the nontrivial choices of a mass parameter and of a thermostat coupling time for the alchemical variable is also investigated, resulting in recommended ranges of 50 to 100 u nm(2) and 0.2 to 0.5 ps, respectively. © 2015 Wiley Periodicals, Inc.

Energy hyperspace for stacking interaction in AU/AU dinucleotide step: Dispersion-corrected density functional theory study.

PubMed

Mukherjee, Sanchita; Kailasam, Senthilkumar; Bansal, Manju; Bhattacharyya, Dhananjay

2014-01-01

Double helical structures of DNA and RNA are mostly determined by base pair stacking interactions, which give them the base sequence-directed features, such as small roll values for the purine-pyrimidine steps. Earlier attempts to characterize stacking interactions were mostly restricted to calculations on fiber diffraction geometries or optimized structure using ab initio calculations lacking variation in geometry to comment on rather unusual large roll values observed in AU/AU base pair step in crystal structures of RNA double helices. We have generated stacking energy hyperspace by modeling geometries with variations along the important degrees of freedom, roll, and slide, which were chosen via statistical analysis as maximally sequence dependent. Corresponding energy contours were constructed by several quantum chemical methods including dispersion corrections. This analysis established the most suitable methods for stacked base pair systems despite the limitation imparted by number of atom in a base pair step to employ very high level of theory. All the methods predict negative roll value and near-zero slide to be most favorable for the purine-pyrimidine steps, in agreement with Calladine's steric clash based rule. Successive base pairs in RNA are always linked by sugar-phosphate backbone with C3'-endo sugars and this demands C1'-C1' distance of about 5.4 Å along the chains. Consideration of an energy penalty term for deviation of C1'-C1' distance from the mean value, to the recent DFT-D functionals, specifically ωB97X-D appears to predict reliable energy contour for AU/AU step. Such distance-based penalty improves energy contours for the other purine-pyrimidine sequences also. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 107-120, 2014. Copyright © 2013 Wiley Periodicals, Inc.

Structural Basis of Activity against Aztreonam and Extended Spectrum Cephalosporins for Two Carbapenem-Hydrolyzing Class D β-Lactamases from Acinetobacter baumannii

DOE PAGES

Mitchell, Joshua M.; Clasman, Jozlyn R.; June, Cynthia M.; ...

2015-02-24

The carbapenem-hydrolyzing class D β-lactamases OXA-23 and OXA-24/40 have emerged world-wide as causative agents for β-lactam antibiotic resistance in Acinetobacter species. Many variants of these enzymes have appeared clinically, including OXA-160 and OXA-225, which both contain a P→S substitution at homologous positions in the OXA-24/40 and OXA-23 backgrounds respectively. We purified OXA-160 and OXA-225 and used steady-state kinetic analysis to compare the substrate profiles of these variants to their parental enzymes, OXA-24/40 and OXA-23. OXA-160 and OXA-225 possess greatly enhanced hydrolytic activities against aztreonam, ceftazidime, cefotaxime and ceftriaxone when compared to OXA-24/40 and OXA-23. These enhanced activities are the resultmore » of much lower Km values, suggesting that the P→S substitution enhances the binding affinity of these drugs. We have determined the structures of the acylated forms of OXA-160 (with ceftazidime and aztreonam) and OXA-225 (ceftazidime). These structures show that the R1 oxyimino side-chain of these drugs occupies a space near the β5-β6 loop and the omega loop of the enzymes. The P→S substitution found in OXA-160 and OXA-225 results in a deviation of the β5-β6 loop, relieving the steric clash with the R1 side-chain carboxypropyl group of aztreonam and ceftazidime. We found that these results reveal worrying trends in the enhancement of substrate spectrum of class D β-lactamases, but may also provide a map for β-lactam improvement.« less

Structural basis for drug and substrate specificity exhibited by FIV encoding a chimeric FIV/HIV protease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Ying-Chuan; Perryman, Alexander L.; Olson, Arthur J.

2011-06-01

Crystal structures of the 6s-98S FIV protease chimera with darunavir and lopinavir bound have been determined at 1.7 and 1.8 Å resolution, respectively. A chimeric feline immunodeficiency virus (FIV) protease (PR) has been engineered that supports infectivity but confers sensitivity to the human immunodeficiency virus (HIV) PR inhibitors darunavir (DRV) and lopinavir (LPV). The 6s-98S PR has five replacements mimicking homologous residues in HIV PR and a sixth which mutated from Pro to Ser during selection. Crystal structures of the 6s-98S FIV PR chimera with DRV and LPV bound have been determined at 1.7 and 1.8 Å resolution, respectively. Themore » structures reveal the role of a flexible 90s loop and residue 98 in supporting Gag processing and infectivity and the roles of residue 37 in the active site and residues 55, 57 and 59 in the flap in conferring the ability to specifically recognize HIV PR drugs. Specifically, Ile37Val preserves tertiary structure but prevents steric clashes with DRV and LPV. Asn55Met and Val59Ile induce a distinct kink in the flap and a new hydrogen bond to DRV. Ile98Pro→Ser and Pro100Asn increase 90s loop flexibility, Gln99Val contributes hydrophobic contacts to DRV and LPV, and Pro100Asn forms compensatory hydrogen bonds. The chimeric PR exhibits a comparable number of hydrogen bonds, electrostatic interactions and hydrophobic contacts with DRV and LPV as in the corresponding HIV PR complexes, consistent with IC{sub 50} values in the nanomolar range.« less

NMR Model of PrgI-SipD Interaction and its Implications in the Needle-Tip Assembly of the Salmonella Type III Secretion System

PubMed Central

Rathinavelan, Thenmalarchelvi; Lara-Tejero, Maria; Lefebre, Matthew; Chatterjee, Srirupa; McShan, Andrew C.; Guo, Da-Chuan; Tang, Chun; Galan, Jorge E.; De Guzman, Roberto N.

2014-01-01

Salmonella and other pathogenic bacteria use the type III secretion system (T3SS) to inject virulence proteins into human cells to initiate infections. The structural component of the T3SS contains a needle and a needle tip. The needle is assembled from PrgI needle protomers and the needle tip is capped with several copies of the SipD tip protein. How a tip protein docks on the needle is unclear. A crystal structure of a PrgI-SipD fusion protein docked on the PrgI needle results in steric clash of SipD at the needle tip when modeled on the recent atomic structure of the needle. Thus, there is currently no good model of how SipD is docked on the PrgI needle tip. Previously, we showed by NMR paramagnetic relaxation enhancement (PRE) methods that a specific region in the SipD coiled-coil is the binding site for PrgI. Others have hypothesized that a domain of the tip protein – the N-terminal α-helical hairpin, has to swing away during the assembly of the needle apparatus. Here, we show by PRE methods that a truncated form of SipD lacking the α-helical hairpin domain binds more tightly to PrgI. Further, PRE-based structure calculations revealed multiple PrgI binding sites on the SipD coiled-coil. Our PRE results together with the recent NMR-derived atomic structure of the Salmonella needle suggest a possible model of how SipD might dock at the PrgI needle tip. SipD and PrgI are conserved in other bacterial T3SSs, thus our results have wider implication in understanding other needle-tip complexes. PMID:24951833

Role of Dynamics in the Autoinhibition and Activation of the Hyperpolarization-activated Cyclic Nucleotide-modulated (HCN) Ion Channels*♦

PubMed Central

VanSchouwen, Bryan; Akimoto, Madoka; Sayadi, Maryam; Fogolari, Federico; Melacini, Giuseppe

2015-01-01

The hyperpolarization-activated cyclic nucleotide-modulated (HCN) ion channels control rhythmicity in neurons and cardiomyocytes. Cyclic AMP allosterically modulates HCN through the cAMP-dependent formation of a tetrameric gating ring spanning the intracellular region (IR) of HCN, to which cAMP binds. Although the apo versus holo conformational changes of the cAMP-binding domain (CBD) have been previously mapped, only limited information is currently available on the HCN IR dynamics, which have been hypothesized to play a critical role in the cAMP-dependent gating of HCN. Here, using molecular dynamics simulations validated and complemented by experimental NMR and CD data, we comparatively analyze HCN IR dynamics in the four states of the thermodynamic cycle arising from the coupling between cAMP binding and tetramerization equilibria. This extensive set of molecular dynamics trajectories captures the active-to-inactive transition that had remained elusive for other CBDs, and it provides unprecedented insight on the role of IR dynamics in HCN autoinhibition and its release by cAMP. Specifically, the IR tetramerization domain becomes more flexible in the monomeric states, removing steric clashes that the apo-CDB structure would otherwise impose. Furthermore, the simulations reveal that the active/inactive structural transition for the apo-monomeric CBD occurs through a manifold of pathways that are more divergent than previously anticipated. Upon cAMP binding, these pathways become disallowed, pre-confining the CBD conformational ensemble to a tetramer-compatible state. This conformational confinement primes the IR for tetramerization and thus provides a model of how cAMP controls HCN channel gating. PMID:25944904

Spin-labeled derivatives of cardiotonic steroids as tools for characterization of the extracellular entrance to the binding site on Na+ ,K+ -ATPase.

PubMed

Guo, Jin-Hua; Jiang, Ren-Wang; Andersen, Jacob Lauwring; Esmann, Mikael; Fedosova, Natalya U

2018-04-24

The information obtained from crystallized complexes of the Na + ,K + -ATPase with cardiotonic steroids (CTS) is not sufficient to explain differences in the inhibitory properties of CTS such as stereoselectivity of CTS binding or effect of glycosylation on the preference to enzyme isoforms. The uncertainty is related to the spatial organization of the hydrophilic cavity at the entrance of the CTS-binding site. Therefore, there is a need to supplement the crystallographic description with data obtained in aqueous solution, where molecules have significant degree of flexibility. This work addresses the applicability of the electron paramagnetic resonance (EPR) method for the purpose. We have designed and synthesized spin-labeled compounds based on the cinobufagin steroid core. The length of the spacer arms between the steroid core and the nitroxide group determines the position of the reporting group (N-O) confined to the binding site. High affinity to Na + ,K + -ATPase is inferred from their ability to inhibit enzymatic activity. The differences between the EPR spectra in the absence and presence of high ouabain concentrations identify the signature peaks originating from the fraction of the spin labels bound within the ouabain site. The degree of perturbations of the EPR spectra depends on the length of the spacer arm. Docking of the compounds into the CTS site suggests which elements of the protein structure might be responsible for interference with the spin label (e.g., steric clashes or immobilization). Thus, the method is suitable for gathering information on the cavity leading to the CTS-binding site in Na + ,K + -ATPase in all conformations with high affinity to CTS. © 2018 Federation of European Biochemical Societies.

Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding.

PubMed

Gui, Miao; Song, Wenfei; Zhou, Haixia; Xu, Jingwei; Chen, Silian; Xiang, Ye; Wang, Xinquan

2017-01-01

The global outbreak of SARS in 2002-2003 was caused by the infection of a new human coronavirus SARS-CoV. The infection of SARS-CoV is mediated mainly through the viral surface glycoproteins, which consist of S1 and S2 subunits and form trimer spikes on the envelope of the virions. Here we report the ectodomain structures of the SARS-CoV surface spike trimer in different conformational states determined by single-particle cryo-electron microscopy. The conformation 1 determined at 4.3 Å resolution is three-fold symmetric and has all the three receptor-binding C-terminal domain 1 (CTD1s) of the S1 subunits in "down" positions. The binding of the "down" CTD1s to the SARS-CoV receptor ACE2 is not possible due to steric clashes, suggesting that the conformation 1 represents a receptor-binding inactive state. Conformations 2-4 determined at 7.3, 5.7 and 6.8 Å resolutions are all asymmetric, in which one RBD rotates away from the "down" position by different angles to an "up" position. The "up" CTD1 exposes the receptor-binding site for ACE2 engagement, suggesting that the conformations 2-4 represent a receptor-binding active state. This conformational change is also required for the binding of SARS-CoV neutralizing antibodies targeting the CTD1. This phenomenon could be extended to other betacoronaviruses utilizing CTD1 of the S1 subunit for receptor binding, which provides new insights into the intermediate states of coronavirus pre-fusion spike trimer during infection.

Using a Fluorescent Cytosine Analogue tC[superscript o] To Probe the Effect of the Y567 to Ala Substitution on the Preinsertion Steps of dNMP Incorporation by RB69 DNA Polymerase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xia, Shuangluo; Beckman, Jeff; Wang, Jimin

2012-10-10

Residues in the nascent base pair binding pocket (NBP) of bacteriophage RB69 DNA polymerase (RB69pol) are responsible for base discrimination. Replacing Tyr567 with Ala leads to greater flexibility in the NBP, increasing the probability of misincorporation. We used the fluorescent cytosine analogue, 1,3-diaza-2-oxophenoxazine (tC{sup o}), to identify preinsertion step(s) altered by NBP flexibility. When tC{sup o} is the templating base in a wild-type (wt) RB69pol ternary complex, its fluorescence is quenched only in the presence of dGTP. However, with the RB69pol Y567A mutant, the fluorescence of tC{sup o} is also quenched in the presence of dATP. We determined the crystalmore » structure of the dATP/tC{sup o}-containing ternary complex of the RB69pol Y567A mutant at 1.9 {angstrom} resolution and found that the incoming dATP formed two hydrogen bonds with an imino-tautomerized form of tC{sup o}. Stabilization of the dATP/tC{sup o} base pair involved movement of the tC{sup o} backbone sugar into the DNA minor groove and required tilting of the tC{sup o} tricyclic ring to prevent a steric clash with L561. This structure, together with the pre-steady-state kinetic parameters and dNTP binding affinity, estimated from equilibrium fluorescence titrations, suggested that the flexibility of the NBP, provided by the Y567 to Ala substitution, led to a more favorable forward isomerization step resulting in an increase in dNTP binding affinity.« less

Molecular evolutionary analysis of vertebrate transducins: a role for amino acid variation in photoreceptor deactivation.

PubMed

Lin, Yi G; Weadick, Cameron J; Santini, Francesco; Chang, Belinda S W

2013-12-01

Transducin is a heterotrimeric G protein that plays a critical role in phototransduction in the rod and cone photoreceptor cells of the vertebrate retina. Rods, highly sensitive cells that recover from photoactivation slowly, underlie dim-light vision, whereas cones are less sensitive, recover more quickly, and underlie bright-light vision. Transducin deactivation is a critical step in photoreceptor recovery and may underlie the functional distinction between rods and cones. Rods and cones possess distinct transducin α subunits, yet they share a common deactivation mechanism, the GTPase activating protein (GAP) complex. Here, we used codon models to examine patterns of sequence evolution in rod (GNAT1) and cone (GNAT2) α subunits. Our results indicate that purifying selection is the dominant force shaping GNAT1 and GNAT2 evolution, but that GNAT2 has additionally been subject to positive selection operating at multiple phylogenetic scales; phylogeny-wide analysis identified several sites in the GNAT2 helical domain as having substantially elevated dN/dS estimates, and branch-site analysis identified several nearby sites as targets of strong positive selection during early vertebrate history. Examination of aligned GNAT and GAP complex crystal structures revealed steric clashes between several positively selected sites and the deactivating GAP complex. This suggests that GNAT2 sequence variation could play an important role in adaptive evolution of the vertebrate visual system via effects on photoreceptor deactivation kinetics and provides an alternative perspective to previous work that focused instead on the effect of GAP complex concentration. Our findings thus further the understanding of the molecular biology, physiology, and evolution of vertebrate visual systems.

Molecular mechanism of R-bicalutamide switching from androgen receptor antagonist to agonist induced by amino acid mutations using molecular dynamics simulations and free energy calculation

NASA Astrophysics Data System (ADS)

Liu, Hongli; Han, Rui; Li, Jiazhong; Liu, Huanxiang; Zheng, Lifang

2016-12-01

R-bicalutamide, a first generation antiandrogen, was used to treat prostate cancer for decades. Although it is very effective at the beginning, resistance appears after 2-3 years of treatment. Mutation of androgen receptor (AR) is considered a main reason for drug resistance. It is reported that AR W741C, W741L, W741C_T877A, T877A, F876L, F876L_T877A and L701H mutations can convert R-bicalutamide from AR antagonist to agonist, but the switching mechanisms are not clear. In this study, molecular dynamics simulations and molecular mechanics generalized Born surface area (MM-GBSA) calculations were performed to analyze the interaction mechanisms between R-bicalutamide and wild type/mutant ARs. The results indicate that helix H12, which lies on the top of AR LBD like a cover, plays a vital role in R-bicalutamide binding. When interacting with AR, the B-ring of R-bicalutamide pushes H12 aside, distorting the coactivator binding site (AF2) resulting in the inactivation of transcription. Several residue mutations appear to enlarge the distance between the B-ring of R-bicalutamide and H12, reducing steric clash, which is conducive to a closed H12 conformation, leading to the formation of the coactivator binding site AF2 and increased transcription. Hydrogen bond and per-residue free energy decomposition analyses are also investigated to explore the interacting mechanisms, and M895 is found to be a key residue in the antagonist mechanism. The obtained molecular mechanisms will aid rational screening and design of novel AR antagonists, even to mutant AR.

Elucidating Hyperconjugation from Electronegativity to Predict Drug Conformational Energy in a High Throughput Manner.

PubMed

Liu, Zhaomin; Pottel, Joshua; Shahamat, Moeed; Tomberg, Anna; Labute, Paul; Moitessier, Nicolas

2016-04-25

Computational chemists use structure-based drug design and molecular dynamics of drug/protein complexes which require an accurate description of the conformational space of drugs. Organic chemists use qualitative chemical principles such as the effect of electronegativity on hyperconjugation, the impact of steric clashes on stereochemical outcome of reactions, and the consequence of resonance on the shape of molecules to rationalize experimental observations. While computational chemists speak about electron densities and molecular orbitals, organic chemists speak about partial charges and localized molecular orbitals. Attempts to reconcile these two parallel approaches such as programs for natural bond orbitals and intrinsic atomic orbitals computing Lewis structures-like orbitals and reaction mechanism have appeared. In the past, we have shown that encoding and quantifying chemistry knowledge and qualitative principles can lead to predictive methods. In the same vein, we thought to understand the conformational behaviors of molecules and to encode this knowledge back into a molecular mechanics tool computing conformational potential energy and to develop an alternative to atom types and training of force fields on large sets of molecules. Herein, we describe a conceptually new approach to model torsion energies based on fundamental chemistry principles. To demonstrate our approach, torsional energy parameters were derived on-the-fly from atomic properties. When the torsional energy terms implemented in GAFF, Parm@Frosst, and MMFF94 were substituted by our method, the accuracy of these force fields to reproduce MP2-derived torsional energy profiles and their transferability to a variety of functional groups and drug fragments were overall improved. In addition, our method did not rely on atom types and consequently did not suffer from poor automated atom type assignments.

A refined model of claudin-15 tight junction paracellular architecture by molecular dynamics simulations

PubMed Central

Alberini, Giulio; Benfenati, Fabio

2017-01-01

Tight-junctions between epithelial cells of biological barriers are specialized molecular structures that regulate the flux of solutes across the barrier, parallel to cell walls. The tight-junction backbone is made of strands of transmembrane proteins from the claudin family, but the molecular mechanism of its function is still not completely understood. Recently, the crystal structure of a mammalian claudin-15 was reported, displaying for the first time the detailed features of transmembrane and extracellular domains. Successively, a structural model of claudin-15-based paracellular channels has been proposed, suggesting a putative assembly that illustrates how claudins associate in the same cell (via cis interactions) and across adjacent cells (via trans interactions). Although very promising, the model offers only a static conformation, with residues missing in the most important extracellular regions and potential steric clashes. Here we present detailed atomic models of paracellular single and double pore architectures, obtained from the putative assembly and refined via structural modeling and all-atom molecular dynamics simulations in double membrane bilayer and water environment. Our results show an overall stable configuration of the complex with a fluctuating pore size. Extracellular residue loops in trans interaction are able to form stable contacts and regulate the size of the pore, which displays a stationary radius of 2.5–3.0 Å at the narrowest region. The side-by-side interactions of the cis configuration are preserved via stable hydrogen bonds, already predicted by cysteine crosslinking experiments. Overall, this work introduces an improved version of the claudin-15-based paracellular channel model that strengthens its validity and that can be used in further computational studies to understand the structural features of tight-junctions regulation. PMID:28863193

Molecular mechanism of R-bicalutamide switching from androgen receptor antagonist to agonist induced by amino acid mutations using molecular dynamics simulations and free energy calculation.

PubMed

Liu, Hongli; Han, Rui; Li, Jiazhong; Liu, Huanxiang; Zheng, Lifang

2016-12-01

R-bicalutamide, a first generation antiandrogen, was used to treat prostate cancer for decades. Although it is very effective at the beginning, resistance appears after 2-3 years of treatment. Mutation of androgen receptor (AR) is considered a main reason for drug resistance. It is reported that AR W741C, W741L, W741C_T877A, T877A, F876L, F876L_T877A and L701H mutations can convert R-bicalutamide from AR antagonist to agonist, but the switching mechanisms are not clear. In this study, molecular dynamics simulations and molecular mechanics generalized Born surface area (MM-GBSA) calculations were performed to analyze the interaction mechanisms between R-bicalutamide and wild type/mutant ARs. The results indicate that helix H12, which lies on the top of AR LBD like a cover, plays a vital role in R-bicalutamide binding. When interacting with AR, the B-ring of R-bicalutamide pushes H12 aside, distorting the coactivator binding site (AF2) resulting in the inactivation of transcription. Several residue mutations appear to enlarge the distance between the B-ring of R-bicalutamide and H12, reducing steric clash, which is conducive to a closed H12 conformation, leading to the formation of the coactivator binding site AF2 and increased transcription. Hydrogen bond and per-residue free energy decomposition analyses are also investigated to explore the interacting mechanisms, and M895 is found to be a key residue in the antagonist mechanism. The obtained molecular mechanisms will aid rational screening and design of novel AR antagonists, even to mutant AR.

Steric parameters, molecular modeling and hydropathic interaction analysis of the pharmacology of para-substituted methcathinone analogues

PubMed Central

Sakloth, F; Kolanos, R; Mosier, P D; Bonano, J S; Banks, M L; Partilla, J S; Baumann, M H; Negus, S S; Glennon, R A

2015-01-01

Background and Purpose There is growing concern over the abuse of certain psychostimulant methcathinone (MCAT) analogues. This study extends an initial quantitative structure–activity relationship (QSAR) investigation that demonstrated important steric considerations of seven 4- (or para-)substituted analogues of MCAT. Specifically, the steric character (Taft's steric ES) of the 4-position substituent affected in vitro potency to induce monoamine release via dopamine and 5-HT transporters (DAT and SERT) and in vivo modulation of intracranial self-stimulation (ICSS). Here, we have assessed the effects of other steric properties of the 4-position substituents. Experimental Approach Definitive steric parameters that more explicitly focus on the volume, width and length of the MCAT 4-position substituents were assessed. In addition, homology models of human DAT and human SERT based upon the crystallized Drosophila DAT were constructed and docking studies were performed, followed by hydropathic interaction (HINT) analysis of the docking results. Key Results The potency of seven MCAT analogues at DAT was negatively correlated with the volume and maximal width of their 4-position substituents, whereas potency at SERT increased as substituent volume and length increased. SERT/DAT selectivity, as well as abuse-related drug effects in the ICSS procedure, also correlated with the same parameters. Docking solutions offered a means of visualizing these findings. Conclusions and Implications These results suggest that steric aspects of the 4-position substituents of MCAT analogues are key determinants of their action and selectivity, and that the hydrophobic nature of these substituents is involved in their potency at SERT. PMID:25522019

Steric stabilization of nonaqueous silicon slips. I - Control of particle agglomeration and packing. II - Pressure casting of powder compacts

NASA Technical Reports Server (NTRS)

Kerkar, Awdhoot V.; Henderson, Robert J. M.; Feke, Donald L.

1990-01-01

The application of steric stabilization to control particle agglomeration and packing of silicon powder in benzene and trichloroethylene is reported. The results provide useful guidelines for controlling unfavorable particle-particle interactions during nonaqueous processing of silicon-based ceramic materials. The application of steric stabilization to the control and improvement of green processing of nonaqueous silicon slips in pressure consolidation is also demonstrated.

The origin of the ligand-controlled regioselectivity in Rh-catalyzed [(2 + 2) + 2] carbocyclizations: steric vs. stereoelectronic effects.

PubMed

Crandell, Douglas W; Mazumder, Shivnath; Evans, P Andrew; Baik, Mu-Hyun

2015-12-01

Density functional theory calculations demonstrate that the reversal of regiochemical outcome of the addition for substituted methyl propiolates in the rhodium-catalyzed [(2 + 2) + 2] carbocyclization with PPh 3 and ( S )-xyl-binap as ligands is both electronically and sterically controlled. For example, the ester functionality polarizes the alkyne π* orbital to favor overlap of the methyl-substituted terminus of the alkyne with the p π -orbital of the alkenyl fragment of the rhodacycle during alkyne insertion with PPh 3 as the ligand. In contrast, the sterically demanding xyl-binap ligand cannot accommodate the analogous alkyne orientation, thereby forcing insertion to occur at the sterically preferred ester terminus, overriding the electronically preferred orientation for alkyne insertion.

THE CLUSTER LENSING AND SUPERNOVA SURVEY WITH HUBBLE: AN OVERVIEW

DOE Office of Scientific and Technical Information (OSTI.GOV)

Postman, Marc; Coe, Dan; Bradley, Larry

2012-04-01

The Cluster Lensing And Supernova survey with Hubble (CLASH) is a 524-orbit Multi-Cycle Treasury Program to use the gravitational lensing properties of 25 galaxy clusters to accurately constrain their mass distributions. The survey, described in detail in this paper, will definitively establish the degree of concentration of dark matter in the cluster cores, a key prediction of structure formation models. The CLASH cluster sample is larger and less biased than current samples of space-based imaging studies of clusters to similar depth, as we have minimized lensing-based selection that favors systems with overly dense cores. Specifically, 20 CLASH clusters are solelymore » X-ray selected. The X-ray-selected clusters are massive (kT > 5 keV) and, in most cases, dynamically relaxed. Five additional clusters are included for their lensing strength ({theta}{sub Ein} > 35'' at z{sub s} = 2) to optimize the likelihood of finding highly magnified high-z (z > 7) galaxies. A total of 16 broadband filters, spanning the near-UV to near-IR, are employed for each 20-orbit campaign on each cluster. These data are used to measure precise ({sigma}{sub z} {approx} 0.02(1 + z)) photometric redshifts for newly discovered arcs. Observations of each cluster are spread over eight epochs to enable a search for Type Ia supernovae at z > 1 to improve constraints on the time dependence of the dark energy equation of state and the evolution of supernovae. We present newly re-derived X-ray luminosities, temperatures, and Fe abundances for the CLASH clusters as well as a representative source list for MACS1149.6+2223 (z 0.544).« less

Submillimeter Observations of CLASH 2882 and the Evolution of Dust in this Galaxy

NASA Technical Reports Server (NTRS)

Dwek, Eli; Staguhn, Johannes; Arendt, Richard G; Kovacs, Attila; Decarli, Roberto; Egami, Eiichi; Michalowski, Michal J.; Rawle, Timothy D.; Toft, Sune; Walter, Fabian

2015-01-01

Two millimeter observations of the MACS J1149.6+2223 cluster have detected a source that was consistent with the location of the lensed MACS 1149-JD galaxy at z = 9.6. A positive identification would have rendered this galaxy as the youngest dust forming galaxy in the universe. Follow up observation with the AzTEC 1.1 mm camera and the IRAM NOrthern Extended Millimeter Array (NOEMA) at 1.3 mm have not confirmed this association. In this paper we show that the NOEMA observations associate the 2 mm source with [PCB2012] 2882,12 source number 2882 in the Cluster Lensing And Supernova survey with Hubble (CLASH) catalog of MACS J1149.6 +2223. This source, hereafter referred to as CLASH 2882, is a gravitationally lensed spiral galaxy at z = 0.99. We combine the Goddard IRAM Superconducting 2-Millimeter Observer (GISMO) 2 mm and NOEMA 1.3 mm fluxes with other (rest frame) UV to far-IR observations to construct the full spectral energy distribution of this galaxy, and derive its star formation history, and stellar and interstellar dust content. The current star formation rate of the galaxy is 54/mu/Solar Mass/yr, and its dust mass is about 5 × 10(exp 7)/mu Solar Mass, where mu is the lensing magnification factor for this source, which has a mean value of 2.7. The inferred dust mass is higher than the maximum dust mass that can be produced by core collapse supernovae and evolved AGB stars. As with many other star forming galaxies, most of the dust mass in CLASH 2882 must have been accreted in the dense phases of the interstellar medium.

13C and 1H nuclear magnetic resonance of methyl-substituted acetophenones and methyl benzoates: steric hindrance and inhibited conjugation.

PubMed

Budesínský, Milos; Kulhánek, Jirí; Böhm, Stanislav; Cigler, Petr; Exner, Otto

2004-10-01

The 1H and 13C NMR spectra of 14 methyl-substituted acetophenones and 14 methyl-substituted methyl benzoates were assigned and interpreted with respect to the conformation of the C(ar)-C(O) bond. The substituent effects are proportional in the two series and can be divided into polar and steric: each has different effects on the 13C SCS of the individual atoms. In the case of C atoms C(O), C(1) and CH3(CO), the steric effects were quantitatively separated by comparing SCS in the ortho and para positions. The steric effects are proportional for the individual C atoms and also to steric effects estimated from other physical quantities. However, they do not depend simply on the angle of torsion phi of the functional group as anticipated hitherto. A better description distinguishes two classes of compounds: sterically not hindered or slightly hindered planar molecules and strongly sterically hindered, markedly non-planar. In order to confirm this reasoning without empirical correlations, the J(C,C) coupling constants were measured for three acetophenone derivatives labeled with 13C in the acetyl methyl group. The constants confirm unambiguously the conformation of 2-methylacetophenone; their zero values are in accord with the conformation of 2,6-dimethylacetophenone. The zero values in the unsubstituted acetophenone are at variance with previous erroneous report but all J(C,C) values are in accord with calculations at the B3LYP/6-311++G(2d,2p)//B3LYP/6-311+G(d,p) level. Copyright 2004 John Wiley & Sons, Ltd.

eIF1 Loop 2 interactions with Met-tRNAi control the accuracy of start codon selection by the scanning preinitiation complex.

PubMed

Thakur, Anil; Hinnebusch, Alan G

2018-05-01

The eukaryotic 43S preinitiation complex (PIC), bearing initiator methionyl transfer RNA (Met-tRNA i ) in a ternary complex (TC) with eukaryotic initiation factor 2 (eIF2)-GTP, scans the mRNA leader for an AUG codon in favorable context. AUG recognition evokes rearrangement from an open PIC conformation with TC in a "P OUT " state to a closed conformation with TC more tightly bound in a "P IN " state. eIF1 binds to the 40S subunit and exerts a dual role of enhancing TC binding to the open PIC conformation while antagonizing the P IN state, necessitating eIF1 dissociation for start codon selection. Structures of reconstituted PICs reveal juxtaposition of eIF1 Loop 2 with the Met-tRNA i D loop in the P IN state and predict a distortion of Loop 2 from its conformation in the open complex to avoid a clash with Met-tRNA i We show that Ala substitutions in Loop 2 increase initiation at both near-cognate UUG codons and AUG codons in poor context. Consistently, the D71A-M74A double substitution stabilizes TC binding to 48S PICs reconstituted with mRNA harboring a UUG start codon, without affecting eIF1 affinity for 40S subunits. Relatively stronger effects were conferred by arginine substitutions; and no Loop 2 substitutions perturbed the rate of TC loading on scanning 40S subunits in vivo. Thus, Loop 2-D loop interactions specifically impede Met-tRNA i accommodation in the P IN state without influencing the P OUT mode of TC binding; and Arg substitutions convert the Loop 2-tRNA i clash to an electrostatic attraction that stabilizes P IN and enhances selection of poor start codons in vivo.

Comment on "Eliminating the major tornado threat in Tornado Alley"

NASA Astrophysics Data System (ADS)

Dahl, Johannes M. L.; Markowski, Paul M.

2014-11-01

The authors draw from half a century of meteorological research to expose flaws in a recent proposal to build 300-m-tall tornado-prevention walls across the U.S. Great Plains. The idea behind the walls is that they would prevent cold and warm air masses from clashing and would therefore suppress tornadoes. The problem with this proposal, however, is that atmospheric fronts ("airmass clashes") are neither a necessary nor a sufficient condition for tornadoes and that the proposed walls would not prevent the formation of fronts in the first place. Additional misconceptions about supercells thunderstorms and tornado formation also are identified.

Eliminating the major tornado threat in Tornado Alley

NASA Astrophysics Data System (ADS)

Tao, R.

2014-06-01

The 2013 devastating tornadoes in Oklahoma, Illinois and other states in Tornado Alley raise an important question: Can we do something to eliminate the major tornado threats in Tornado Alley? Violent tornadoes in Tornado Alley start from the clash-between northbound warm air flow and southbound cold air flow. As there is no mountain in Tornado Alley ranging from west to east to weaken or block the air flows, some clashes are violent, creating vortex turbulence called supercells. These supercells are initially in horizontal spinning motion at the lower atmosphere and then tilt as the air turns to rise in the storm's updraft, creating a component of spin around a vertical axis. About 30% of supercells develop into tornadoes, causing tremendous damages. Here we show that if we build three east-west great walls in the American Midwest, 300 m high and 50 m wide, one in North Dakota, one passing Oklahoma to east and the third one in the south Texas and Louisiana, we will weaken or block such air mass clashes and therefore diminish the major tornado threat in the Tornado Alley forever. We may also first build such great walls locally at some areas with frequent devastating tornado outbreaks and then gradually extend them.

Theoretical analysis of the rotational barrier of ethane.

PubMed

Mo, Yirong; Gao, Jiali

2007-02-01

The understanding of the ethane rotation barrier is fundamental for structural theory and the conformational analysis of organic molecules and requires a consistent theoretical model to differentiate the steric and hyperconjugation effects. Due to recently renewed controversies over the barrier's origin, we developed a computational approach to probe the rotation barriers of ethane and its congeners in terms of steric repulsion, hyperconjugative interaction, and electronic and geometric relaxations. Our study reinstated that the conventional steric repulsion overwhelmingly dominates the barriers.

The Crystal Structure of a Ternary Complex of Betaine Aldehyde Dehydrogenase from Pseudomonas aeruginosa Provides New Insight Into the Reaction Mechansim and Shows A Novel Binding Mode of the 2'-Phosphate of NADP+ and A Novel Cation Binding Site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gonzalez-Segura, L.; Rudino-Pinera, E; Munoz-Clares, R

2009-01-01

In the human pathogen Pseudomonas aeruginosa, the NAD(P)+-dependent betaine aldehyde dehydrogenase (PaBADH) may play the dual role of assimilating carbon and nitrogen from choline or choline precursors-abundant at infection sites-and producing glycine betaine and NADPH, potentially protective against the high-osmolarity and oxidative stresses prevalent in the infected tissues. Disruption of the PaBADH gene negatively affects the growth of bacteria, suggesting that this enzyme could be a target for antibiotic design. PaBADH is one of the few ALDHs that efficiently use NADP+ and one of the even fewer that require K+ ions for stability. Crystals of PaBADH were obtained under aerobicmore » conditions in the presence of 2-mercaptoethanol, glycerol, NADP+ and K+ ions. The three-dimensional structure was determined at 2.1-A resolution. The catalytic cysteine (C286, corresponding to C302 of ALDH2) is oxidized to sulfenic acid or forms a mixed disulfide with 2-mercaptoethanol. The glutamyl residue involved in the deacylation step (E252, corresponding to E268 of ALDH2) is in two conformations, suggesting a proton relay system formed by two well-conserved residues (E464 and K162, corresponding to E476 and K178, respectively, of ALDH2) that connects E252 with the bulk water. In some active sites, a bound glycerol molecule mimics the thiohemiacetal intermediate; its hydroxyl oxygen is hydrogen bonded to the nitrogen of the amide groups of the side chain of the conserved N153 (N169 of ALDH2) and those of the main chain of C286, which form the 'oxyanion hole.' The nicotinamide moiety of the nucleotide is not observed in the crystal, and the adenine moiety binds in the usual way. A salt bridge between E179 (E195 of ALDH2) and R40 (E53 of ALDH2) moves the carboxylate group of the former away from the 2?-phosphate of the NADP+, thus avoiding steric clashes and/or electrostatic repulsion between the two groups. Finally, the crystal shows two K+ binding sites per subunit. One is in an intrasubunit cavity that we found to be present in all known ALDH structures. The othersingle bondnot described before for any ALDH but most likely present in most of themsingle bondis located in between the dimeric unit, helping structure a region involved in coenzyme binding and catalysis. This may explain the effects of K+ ions on the activity and stability of PaBADH.« less

Fisher information and steric effect: study of the internal rotation barrier of ethane.

PubMed

Esquivel, Rodolfo O; Liu, Shubin; Angulo, Juan Carlos; Dehesa, Jesús S; Antolín, Juan; Molina-Espíritu, Moyocoyani

2011-05-05

On the basis of a density-based quantification of the steric effect [Liu, S. B. J. Chem. Phys.2007, 126, 244103], the origin of the internal rotation barrier between the eclipsed and staggered conformers of ethane is systematically investigated in this work from an information-theoretical point of view by using the Fisher information measure in conjugated spaces. Two kinds of computational approaches are considered in this work: adiabatic (with optimal structure) and vertical (with fixed geometry). The analyses are performed systematically by following, in each case, the conformeric path by changing the dihedral angle from 0 to 180° . This is calculated at the HF, MP2, B3LYP, and CCSD(T) levels of theory and with several basis sets. Selected descriptors of the densities are utilized to support the observations. Our results show that in the adiabatic case the eclipsed conformer possesses a larger steric repulsion than the staggered conformer, but in the vertical cases the staggered conformer retains a larger steric repulsion. Our results verify the plausibility for defining and computing the steric effect in the post-Hartree-Fock level of theory according to the scheme proposed by Liu.

"My view that disability is okay sometimes clashes": experiences of two disabled occupational therapists.

PubMed

Chacala, Aneta; McCormack, Cathy; Collins, Bethan; Beagan, Brenda L

2014-03-01

While disability is the focus of much attention in occupational therapy, there has been little attention paid to disability within the profession. Disabled therapists not only bring valuable perspectives on disability, but also pose important challenges to taken-for-granted assumptions about impairment and disability within the profession. At the same time, their cultural beliefs and values may clash with core assumptions of the profession. This study analyses interview data from two disabled occupational therapists, part of a larger study with cultural minority therapists. Semi-structured interviews explored their experiences of professional practice in the context of societal belief in the superiority of non-disabled and "normal" ways of doing and being. Some cultural values of participants clashed with the values and beliefs of their profession, particularly concerning independence. Negative attitudes of colleagues and managers were the key barriers to practice. The responsibility for bridging the disabled/non-disabled cultural divide rested with the disabled therapists, exacerbating inequity. Nonetheless, these therapists believed their disability experiences had advantages for practice. Disabled therapists may be required to engage in invisible work to communicate across cultural differences, and to educate others. Respectful openness to difference could enhance the practice competence of both disabled therapists and their non-disabled colleagues. This demands critical reflexive attention to ableism within the profession.

In vitro interactions between amphotericin B and hydrocortisone: potential implications for intrathecal therapy.

PubMed

Hodge, Greg; Cohen, Stuart H; Thompson, George R

2015-09-01

Fungal meningitis remains a severe and often lethal infection requiring aggressive antifungal therapy and in refractory cases the use of intrathecal amphotericin B (AmB). Administration of amphotericin B by this method may result in clinically apparent adverse reactions such as paresthesias, radiculitis, or myelopathy. Coadministration of hydrocortisone is therefore often given in an attempt to avoid these effects; however, the potential consequences of this approach on fungal growth or on drug synergy/antagonism had not previously been assessed. We used the checkerboard titration broth microdilution method to analyze interactions by fractional inhibitory concentration indices (FICIs). The combination of amphotericin B and hydrocortisone resulted in synergy or indifference against all isolates (Candida, Cryptococcus, and Coccidioides) during in vitro testing at low concentrations. Antagonism was observed using higher hydrocortisone concentrations (those not observed in vivo) suggesting possible steric hindrance or binding to AmB may occur at doses unlikely to be present during clinical care. Concurrent hydrocortisone and AmB administration should not be avoided due to in vitro antagonism concerns. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Sulfur-Specific Microbial Desulfurization of Sterically Hindered Analogs of Dibenzothiophene

PubMed Central

Lee, M. K.; Senius, J. D.; Grossman, M. J.

1995-01-01

Dibenzothiophenes (DBTs) bearing alkyl substitutions adjacent to the sulfur atom, such as 4,6-diethyldibenzothiophene (4,6-DEDBT), are referred to as sterically hindered with regard to access to the sulfur moiety. By using enrichment cultures with 4,6-DEDBT as the sole sulfur source, bacterial isolates which selectively remove sulfur from sterically hindered DBTs were obtained. The isolates were tentatively identified as Arthrobacter species. 4,6-DEDBT sulfone was shown to be an intermediate in the 4,6-DEDBT desulfurization pathway, and 2-hydroxy-3,3(prm1)-diethylbiphenyl (HDEBP) was identified as the sulfur-free end product. PMID:16535189

Right or wrong? The brain's fast response to morally objectionable statements.

PubMed

Van Berkum, Jos J A; Holleman, Bregje; Nieuwland, Mante; Otten, Marte; Murre, Jaap

2009-09-01

How does the brain respond to statements that clash with a person's value system? We recorded event-related brain potentials while respondents from contrasting political-ethical backgrounds completed an attitude survey on drugs, medical ethics, social conduct, and other issues. Our results show that value-based disagreement is unlocked by language extremely rapidly, within 200 to 250 ms after the first word that indicates a clash with the reader's value system (e.g., "I think euthanasia is an acceptable/unacceptable..."). Furthermore, strong disagreement rapidly influences the ongoing analysis of meaning, which indicates that even very early processes in language comprehension are sensitive to a person's value system. Our results testify to rapid reciprocal links between neural systems for language and for valuation.

Influence of nonelectrostatic ion-ion interactions on double-layer capacitance

NASA Astrophysics Data System (ADS)

Zhao, Hui

2012-11-01

Recently a Poisson-Helmholtz-Boltzmann (PHB) model [Bohinc , Phys. Rev. EPLEEE81539-375510.1103/PhysRevE.85.031130 85, 031130 (2012)] was developed by accounting for solvent-mediated nonelectrostatic ion-ion interactions. Nonelectrostatic interactions are described by a Yukawa-like pair potential. In the present work, we modify the PHB model by adding steric effects (finite ion size) into the free energy to derive governing equations. The modified PHB model is capable of capturing both ion specificity and ion crowding. This modified model is then employed to study the capacitance of the double layer. More specifically, we focus on the influence of nonelectrostatic ion-ion interactions on charging a double layer near a flat surface in the presence of steric effects. We numerically compute the differential capacitance as a function of the voltage under various conditions. At small voltages and low salt concentrations (dilute solution), we find out that the predictions from the modified PHB model are the same as those from the classical Poisson-Boltzmann theory, indicating that nonelectrostatic ion-ion interactions and steric effects are negligible. At moderate voltages, nonelectrostatic ion-ion interactions play an important role in determining the differential capacitance. Generally speaking, nonelectrostatic interactions decrease the capacitance because of additional nonelectrostatic repulsion among excess counterions inside the double layer. However, increasing the voltage gradually favors steric effects, which induce a condensed layer with crowding of counterions near the electrode. Accordingly, the predictions from the modified PHB model collapse onto those computed by the modified Poisson-Boltzmann theory considering steric effects alone. Finally, theoretical predictions are compared and favorably agree with experimental data, in particular, in concentrated solutions, leading one to conclude that the modified PHB model adequately predicts the diffuse-charge dynamics of the double layer with ion specificity and steric effects.

Steric, Quantum, and Electrostatic Effects on SN2 Reaction Barriers in Gas Phase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Shubin; Hu, Hao; Pedersen, Lee G.

2010-05-13

Biomolecular nucleophilic substitution reactions, S{sub N}2, are fundamental and commonplace in chemistry. It is the well-documented experimental finding in the literature that vicinal substitution with bulkier groups near the reaction center significantly slows the reaction due to steric hindrance, but theoretical understanding in the quantitative manner about factors dictating the S{sub N}2 reaction barrier height is still controversial. In this work, employing the new quantification approach that we recently proposed for the steric effect from the density functional theory framework, we investigate the relative contribution of three independent effects—steric, electrostatic, and quantum—to the S{sub N}2 barrier heights in gas phasemore » for substituted methyl halide systems, R{sub 1}R{sub 2}R{sub 3}CX, reacting with the fluorine anion, where R{sub 1}, R{sub 2}, and R{sub 3} denote substituting groups and X = F or Cl. We found that in accordance with the experimental finding, for these systems, the steric effect dominates the transition state barrier, contributing positively to barrier heights, but this contribution is largely compensated by the negative, stabilizing contribution from the quantum effect due to the exchange-correlation interactions. Moreover, we find that it is the component from the electrostatic effect that is linearly correlated with the S{sub N}2 barrier height for the systems investigated in the present study. In addition, we compared our approach with the conventional method of energy decomposition in density functional theory as well as examined the steric effect from the wave function theory for these systems via natural bond orbital analysis.« less

OXIDATION OF CYCLOHEXANE WITH AIR CATALYZED BY A STERICALLY HINDERED IRON (II) COMPLEX

EPA Science Inventory

Oxidation of Cyclohexane with Air Catalyzed by a Sterically Hindered Iron(II) Complex.


Thomas M. Becker, Michael A. Gonzalez*

United States Environmental Protection Agency; National Risk Management Research Laboratory; Sustainable Technology Division; Clean Pr...

The origin of the ligand-controlled regioselectivity in Rh-catalyzed [(2 + 2) + 2] carbocyclizations: steric vs. stereoelectronic effects† †Electronic supplementary information (ESI) available: Computational details, Cartesian coordinates and vibrational frequencies of all optimized structures. See DOI: 10.1039/c5sc02307f Click here for additional data file.

PubMed Central

Crandell, Douglas W.; Mazumder, Shivnath

2015-01-01

Density functional theory calculations demonstrate that the reversal of regiochemical outcome of the addition for substituted methyl propiolates in the rhodium-catalyzed [(2 + 2) + 2] carbocyclization with PPh3 and (S)-xyl-binap as ligands is both electronically and sterically controlled. For example, the ester functionality polarizes the alkyne π* orbital to favor overlap of the methyl-substituted terminus of the alkyne with the pπ-orbital of the alkenyl fragment of the rhodacycle during alkyne insertion with PPh3 as the ligand. In contrast, the sterically demanding xyl-binap ligand cannot accommodate the analogous alkyne orientation, thereby forcing insertion to occur at the sterically preferred ester terminus, overriding the electronically preferred orientation for alkyne insertion. PMID:28757978

Parameterization of phosphine ligands demonstrates enhancement of nickel catalysis via remote steric effects.

PubMed

Wu, Kevin; Doyle, Abigail G

2017-08-01

The field of Ni-catalysed cross-coupling has seen rapid recent growth because of the low cost of Ni, its earth abundance, and its ability to promote unique cross-coupling reactions. Whereas advances in the related field of Pd-catalysed cross-coupling have been driven by ligand design, the development of ligands specifically for Ni has received minimal attention. Here, we disclose a class of phosphines that enable the Ni-catalysed Csp 3 Suzuki coupling of acetals with boronic acids to generate benzylic ethers, a reaction that failed with known ligands for Ni and designer phosphines for Pd. Using parameters to quantify phosphine steric and electronic properties together with regression statistical analysis, we identify a model for ligand success. The study suggests that effective phosphines feature remote steric hindrance, a concept that could guide future ligand design tailored to Ni. Our analysis also reveals that two classic descriptors for ligand steric environment-cone angle and % buried volume-are not equivalent, despite their treatment in the literature.

Parameterization of phosphine ligands demonstrates enhancement of nickel catalysis via remote steric effects

NASA Astrophysics Data System (ADS)

Wu, Kevin; Doyle, Abigail G.

2017-08-01

The field of Ni-catalysed cross-coupling has seen rapid recent growth because of the low cost of Ni, its earth abundance, and its ability to promote unique cross-coupling reactions. Whereas advances in the related field of Pd-catalysed cross-coupling have been driven by ligand design, the development of ligands specifically for Ni has received minimal attention. Here, we disclose a class of phosphines that enable the Ni-catalysed Csp3 Suzuki coupling of acetals with boronic acids to generate benzylic ethers, a reaction that failed with known ligands for Ni and designer phosphines for Pd. Using parameters to quantify phosphine steric and electronic properties together with regression statistical analysis, we identify a model for ligand success. The study suggests that effective phosphines feature remote steric hindrance, a concept that could guide future ligand design tailored to Ni. Our analysis also reveals that two classic descriptors for ligand steric environment—cone angle and % buried volume—are not equivalent, despite their treatment in the literature.

Coatings with controlled porosity and chemical properties

DOEpatents

Frye, Gregory C.; Brinker, C. Jeffrey; Doughty, Daniel H.; Bein, Thomas; Moller, Karin

1996-01-01

Coatings and sensors having both steric and chemical selectivity. Controlled porosity provides the steric selectivity, whereas chemically tailored film properties, using controlled composition or modification by coupling agents, chemical species replacement, or chemical species within pores, provide the chemical selectivity. Single or multiple layers may be provided.

Coatings with controlled porosity and chemical properties

DOEpatents

Frye, Gregory C.; Brinker, C. Jeffrey; Doughty, Daniel H.; Bein, Thomas; Moller, Karin

1993-01-01

Coatings and sensors having both steric and chemical selectivity. Controlled porosity provides the steric selectivity, whereas chemically tailored film properties, using controlled composition or modification by coupling agents, chemical species replacement, or chemical species within pores, provide the chemical selectivity. Single or multiple layers may be provided.

British Muslims and the UK government's 'war on terror' within: evidence of a clash of civilizations or emergent de-civilizing processes?

PubMed

Vertigans, Stephen

2010-03-01

In the immediate aftermath of the September 2001 attacks on America, defending civilization was quickly established at the core of the 'war on terror'. Unintentionally or otherwise this incorporation of civilization connected with Samuel Huntington's 'Clash of Civilizations' thesis. Within the 'war on terror' the dark side of counterterrorism has become apparent through international practices like extrajudicial killing, extraordinary rendition and torture. The impact of Western governments' policies upon their indigenous Muslim populations has also been problematic but social and political analysis has been relatively limited. This paper seeks to help address the scarcity of sociological contributions. Hidden costs of the UK government's attempts to utilize violence and enhance social constraints within the nation-state are identified. It is argued that although counterterrorism strategies are contributing to a self-fulfilling spiral of hatred that could be considered evidence in support of the 'Clash of Civilizations', the thesis is unhelpful when trying to grasp the underlying processes. Instead the paper draws upon Norbert Elias's application of the concepts of 'civilizing' and 'de-civilizing' to help improve levels of understanding about the processes and consequences of particular Muslim communities being targeted by security forces. The paper concludes with an exploration of the majority of the population's acquiescence and willingness to accept restraints upon Muslims in order to safeguard their own security.

Clash of symmetries in a Randall-Sundrum-like spacetime

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dando, Gareth; George, Damien P.; Volkas, Raymond R.

2005-08-15

We present a toy model that exhibits clash-of-symmetries style Higgs field kink configurations in a Randall-Sundrum-like spacetime. The model has two complex scalar fields {phi}{sub 1,2}, with a sextic potential obeying global U(1)xU(1) and discrete {phi}{sub 1}{r_reversible}{phi}{sub 2} interchange symmetries. The scalar fields are coupled to 4+1 dimensional gravity endowed with a bulk cosmological constant. We show that the coupled Einstein-Higgs field equations have an interesting analytic solution provided the sextic potential adopts a particular form. The 4+1 metric is shown to be that of a smoothed-out Randall-Sundrum type of spacetime. The thin-brane Randall-Sundrum limit, whereby the Higgs field kinksmore » become step functions, is carefully defined in terms of the fundamental parameters in the action. The 'clash-of-symmetries' feature, defined in previous papers, is manifested here through the fact that both of the U(1) symmetries are spontaneously broken at all nonasymptotic points in the extra dimension w. One of the U(1)'s is asymptotically restored as w{yields}-{infinity}, with the other U(1) restored as w{yields}+{infinity}. The spontaneously broken discrete symmetry ensures topological stability. In the gauged version of this model we find new flat-space solutions, but in the warped metric case we have been unable to find any solutions with nonzero gauge fields.« less

Coatings with controlled porosity and chemical properties

DOEpatents

Frye, G.C.; Brinker, C.J.; Doughty, D.H.; Bein, T.; Moller, K.

1996-12-31

Coatings and sensors are disclosed having both steric and chemical selectivity. Controlled porosity provides the steric selectivity, whereas chemically tailored film properties, using controlled composition or modification by coupling agents, chemical species replacement, or chemical species within pores, provide the chemical selectivity. Single or multiple layers may be provided. 7 figs.

Coatings with controlled porosity and chemical properties

DOEpatents

Frye, G.C.; Brinker, C.J.; Doughty, D.H.; Bein, T.; Moller, K.

1993-07-06

Coatings and sensors are described having both steric and chemical selectivity. Controlled porosity provides the steric selectivity, whereas chemically tailored film properties, using controlled composition or modification by coupling agents, chemical species replacement, or chemical species within pores, provide the chemical selectivity. Single or multiple layers may be provided.

Sterically shielded diboron-containing metallocene olefin polymerization catalysts

DOEpatents

Marks, Tobin J.; Ja, Li; Yang, Xinmin

1995-09-05

A non-coordinating anion, preferably containing a sterically shielded diboron hydride, if combined with a cyclopenta-dienyl-substituted metallocene cation component, such as a zirconocene metallocene, is a useful olefin polymerization catalyst component. The anion preferably has the formula ##STR1## where R is branched lower alkyl, such as t-butyl.

Fast "hyperlayer" separation development in sedimentation field flow fractionation.

PubMed

Kassab, James R; Cardot, Philippe J P; Zahoransky, Richard A; Battu, Serge

2005-11-05

Specific prototypes of sedimentation field flow fractionation devices (SdFFF) have been developed with relative success for cell sorting. However, no data are available to compare these apparatus with commercial ones. In order to compare with other devices mainly used for non-biological species, biocompatible systems were used for standard particle (latex: 3-10 microm of different size dispersities) separation development. In order to enhance size dependent separations, channels of reduced thickness were used (80 and 100 microm) and channel/carrier-phase equilibration procedures were necessary. For sample injection, the use of inlet tubing linked to the FFF accumulation wall, common for cell sorting, can be extended to latex species when they are eluted in the Steric Hyperlayer elution mode. It avoids any primary relaxation steps (stop flow injection procedure) simplifying series of elution processing. Mixtures composed of four different monodispersed latex beads can be eluted in 6 min with 100 microm channel thickness.

Computer-aided structure-affinity relationships in a set of piperazine and 3,8-diazabicyclo[3.2.1]octane derivatives binding to the μ-opioid receptor

NASA Astrophysics Data System (ADS)

Barlocco, Daniela; Cignarella, Giorgio; Greco, Giovanni; Novellino, Ettore

1993-10-01

Molecular modeling studies were carried out on a set of piperazine and 3,8-diazabicyclo[3.2.1]octane derivatives with the aim to highlight the main factors modulating their affinity for the μ-opioid receptor. Structure-affinity relationships were developed with the aid of molecular mechanics and semiempirical quantum-mechanics methods. According to our proposed pharmacodynamic model, the binding to the μ-receptor is promoted by the following physico-chemical features: the presence of hydrocarbon fragments on the nitrogen ring frame capable of interacting with one of two hypothesized hydrophobic receptor pockets; a `correct' orientation of an N-propionyl side chain so as to avoid a sterically hindered region of the receptor; the possibility of accepting a hydrogen bond from a receptor site complementary to the morphine phenol oxygen.

Structural evolution of glycan recognition by a family of potent HIV antibodies.

PubMed

Garces, Fernando; Sok, Devin; Kong, Leopold; McBride, Ryan; Kim, Helen J; Saye-Francisco, Karen F; Julien, Jean-Philippe; Hua, Yuanzi; Cupo, Albert; Moore, John P; Paulson, James C; Ward, Andrew B; Burton, Dennis R; Wilson, Ian A

2014-09-25

The HIV envelope glycoprotein (Env) is densely covered with self-glycans that should help shield it from recognition by the human immune system. Here, we examine how a particularly potent family of broadly neutralizing antibodies (Abs) has evolved common and distinct structural features to counter the glycan shield and interact with both glycan and protein components of HIV Env. The inferred germline antibody already harbors potential binding pockets for a glycan and a short protein segment. Affinity maturation then leads to divergent evolutionary branches that either focus on a single glycan and protein segment (e.g., Ab PGT124) or engage multiple glycans (e.g., Abs PGT121-123). Furthermore, other surrounding glycans are avoided by selecting an appropriate initial antibody shape that prevents steric hindrance. Such molecular recognition lessons are important for engineering proteins that can recognize or accommodate glycans. Copyright © 2014 Elsevier Inc. All rights reserved.

Emergence of collective motion in bacterial suspensions

NASA Astrophysics Data System (ADS)

Liu, Song

It is well known that bacterial suspensions will exhibit collective motion at high concentrations, in which both steric and hydrodynamic interactions play important roles. We aim to investigate whether steric and hydrodynamic interactions are of equal importance to the emergence of collective motion. Here we will present our efforts to experimentally tune the relative strength of these interactions in bacterial suspensions. Our preliminary results suggest that the transition to collective motion may depend on the interplay between steric and hydrodynamic interactions. Mailing address: Room 306 Science Centre North Block, The Chinese University of Hong Kong, Shatin, N.T. Hong Kong SAR. Phone: +852-3943-6354. Fax: +852-2603-5204. E-mail: songliuphy@gmail.com.

Conservative Tryptophan Mutants of the Protein Tyrosine Phosphatase YopH Exhibit Impaired WPD-Loop Function and Crystallize with Divanadate Esters in Their Active Sites

PubMed Central

Moise, Gwendolyn; Gallup, Nathan M.; Alexandrova, Anastassia N.; Hengge, Alvan C.; Johnson, Sean J.

2016-01-01

Catalysis in protein tyrosine phosphatases (PTPs) involves movement of a protein loop called the WPD loop that brings a conserved aspartic acid into the active site to function as a general acid. Mutation of the tryptophan in the WPD loop of the PTP YopH to any other residue with a planar, aromatic side chain (phenylalanine, tyrosine, or histidine) disables general acid catalysis. Crystal structures reveal these conservative mutations leave this critical loop in a catalytically unproductive, quasi-open position. Although the loop positions in crystal structures are similar for all three conservative mutants, the reasons inhibiting normal loop closure differ for each mutant. In the W354F and W354Y mutants, steric clashes result from six-membered rings occupying the position of the five-membered ring of the native indole side chain. The histidine mutant dysfunction results from new hydrogen bonds stabilizing the unproductive position. The results demonstrate how even modest modifications can disrupt catalytically important protein dynamics. Crystallization of all the catalytically compromised mutants in the presence of vanadate gave rise to vanadate dimers at the active site. In W354Y and W354H, a divanadate ester with glycerol is observed. Such species have precedence in solution and are known from the small molecule crystal database. Such species have not been observed in the active site of a phosphatase, as a functional phosphatase would rapidly catalyze their decomposition. The compromised functionality of the mutants allows the trapping of species that undoubtedly form in solution and are capable of binding at the active sites of PTPs, and, presumably, other phosphatases. In addition to monomeric vanadate, such higher-order vanadium-based molecules are likely involved in the interaction of vanadate with PTPs in solution. PMID:26445170

Crystal structures and mutagenesis of PPP-family ser/thr protein phosphatases elucidate the selectivity of cantharidin and novel norcantharidin-based inhibitors of PP5C.

PubMed

Chattopadhyay, Debasish; Swingle, Mark R; Salter, Edward A; Wood, Eric; D'Arcy, Brandon; Zivanov, Catherine; Abney, Kevin; Musiyenko, Alla; Rusin, Scott F; Kettenbach, Arminja; Yet, Larry; Schroeder, Chad E; Golden, Jennifer E; Dunham, Wade H; Gingras, Anne-Claude; Banerjee, Surajit; Forbes, David; Wierzbicki, Andrzej; Honkanen, Richard E

2016-06-01

Cantharidin is a natural toxin and an active constituent in a traditional Chinese medicine used to treat tumors. Cantharidin acts as a semi-selective inhibitor of PPP-family ser/thr protein phosphatases. Despite sharing a common catalytic mechanism and marked structural similarity with PP1C, PP2AC and PP5C, human PP4C was found to be insensitive to the inhibitory activity of cantharidin. To explore the molecular basis for this selectivity, we synthesized and tested novel C5/C6-derivatives designed from quantum-based modeling of the interactions revealed in the co-crystal structures of PP5C in complex with cantharidin. Structure-activity relationship studies and analysis of high-resolution (1.25Å) PP5C-inhibitor co-crystal structures reveal close contacts between the inhibitor bridgehead oxygen and both a catalytic metal ion and a non-catalytic phenylalanine residue, the latter of which is substituted by tryptophan in PP4C. Quantum chemistry calculations predicted that steric clashes with the bulkier tryptophan side chain in PP4C would force all cantharidin-based inhibitors into an unfavorable binding mode, disrupting the strong coordination of active site metal ions observed in the PP5C co-crystal structures, thereby rendering PP4C insensitive to the inhibitors. This prediction was confirmed by inhibition studies employing native human PP4C. Mutation of PP5C (F446W) and PP1C (F257W), to mimic the PP4C active site, resulted in markedly suppressed sensitivity to cantharidin. These observations provide insight into the structural basis for the natural selectivity of cantharidin and provide an avenue for PP4C deselection. The novel crystal structures also provide insight into interactions that provide increased selectivity of the C5/C6 modifications for PP5C versus other PPP-family phosphatases. Copyright © 2016 Elsevier Inc. All rights reserved.

Antibodies Specifically Targeting a Locally Misfolded Region of Tumor Associated EGFR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garrett, T.; Burgess, A; Gan, H

2009-01-01

Epidermal Growth Factor Receptor (EGFR) is involved in stimulating the growth of many human tumors, but the success of therapeutic agents has been limited in part by interference from the EGFR on normal tissues. Previously, we reported an antibody (mab806) against a truncated form of EGFR found commonly in gliomas. Remarkably, it also recognizes full-length EGFR on tumor cells but not on normal cells. However, the mechanism for this activity was unclear. Crystallographic structures for Fab:EGFR{sub 287-302} complexes of mAb806 (and a second, related antibody, mAb175) show that this peptide epitope adopts conformations similar to those found in the wtEGFR.more » However, in both conformations observed for wtEGFR, tethered and untethered, antibody binding would be prohibited by significant steric clashes with the CR1 domain. Thus, these antibodies must recognize a cryptic epitope in EGFR. Structurally, it appeared that breaking the disulfide bond preceding the epitope might allow the CR1 domain to open up sufficiently for antibody binding. The EGFR{sub C271A/C283A} mutant not only binds mAb806, but binds with 1:1 stoichiometry, which is significantly greater than wtEGFR binding. Although mAb806 and mAb175 decrease tumor growth in xenografts displaying mutant, overexpressed, or autocrine stimulated EGFR, neither antibody inhibits the in vitro growth of cells expressing wtEGFR. In contrast, mAb806 completely inhibits the ligand-associated stimulation of cells expressing EGFR{sub C271A/C283A}. Clearly, the binding of mAb806 and mAb175 to the wtEGFR requires the epitope to be exposed either during receptor activation, mutation, or overexpression. This mechanism suggests the possibility of generating antibodies to target other wild-type receptors on tumor cells.« less

Rational design of aminoacyl-tRNA synthetase specific for p-acetyl-L-phenylalanine.

PubMed

Sun, Renhua; Zheng, Heng; Fang, Zhengzhi; Yao, Wenbing

2010-01-01

The Methanococcus jannaschii tRNA(Tyr)/tyrosyl-tRNA synthetase pair has been engineered to incorporate unnatural amino acids into proteins in Escherichia coli site-specifically. In order to add other unnatural amino acids into proteins by this approach, the amino acid binding site of M. jannaschii tyrosyl-tRNA synthetase need to be mutated. The crystal structures of M. jannaschii tyrosyl-tRNA synthetase and its mutations were determined, which provided an opportunity to design aminoacyl-tRNA synthetases specific for other unnatural amino acids. In our study, we attempted to design aminoacyl-tRNA synthetases being able to deliver p-acetyl-L-phenylalanine into proteins. p-Acetyl-L-phenylalanine was superimposed on tyrosyl in M. jannaschii tyrosyl-tRNA synthetase-tyrosine complex. Tyr32 needed to be changed to non-polar amino acid with shorter side chain, Val, Leu, Ile, Gly or Ala, in order to reduce steric clash and provide hydrophobic environment to acetyl on p-acetyl-L-phenylalanine. Asp158 and Ile159 would be changed to specific amino acids for the same reason. So we designed 60 aminoacyl-tRNA synthetases. Binding of these aminoacyl-tRNA synthetases with p-acetyl-L-phenylalanine indicated that only 15 of them turned out to be able to bind p-acetyl-L-phenylalanine with reasonable poses. Binding affinity computation proved that the mutation of Tyr32Leu and Asp158Gly benefited p-acetyl-L-phenylalanine binding. And two of the designed aminoacyl-tRNA synthetases had considerable binding affinities. They seemed to be very promising to be able to incorporate p-acetyl-L-phenylalanine into proteins in E. coli. The results show that the combination of homology modeling and molecular docking is a feasible method to filter inappropriate mutations in molecular design and point out beneficial mutations. Copyright 2009 Elsevier Inc. All rights reserved.

Temperature rise, sea level rise and increased radiative forcing - an application of cointegration methods

NASA Astrophysics Data System (ADS)

Schmith, Torben; Thejll, Peter; Johansen, Søren

2016-04-01

We analyse the statistical relationship between changes in global temperature, global steric sea level and radiative forcing in order to reveal causal relationships. There are in this, however, potential pitfalls due to the trending nature of the time series. We therefore apply a statistical method called cointegration analysis, originating from the field of econometrics, which is able to correctly handle the analysis of series with trends and other long-range dependencies. Further, we find a relationship between steric sea level and temperature and find that temperature causally depends on the steric sea level, which can be understood as a consequence of the large heat capacity of the ocean. This result is obtained both when analyzing observed data and data from a CMIP5 historical model run. Finally, we find that in the data from the historical run, the steric sea level, in turn, is driven by the external forcing. Finally, we demonstrate that combining these two results can lead to a novel estimate of radiative forcing back in time based on observations.

St. John's Wort (image)

MedlinePlus

The herb St. John's Wort is believed to be helpful in relieving mild to moderate depression, but should only be taken under a physician's supervision. St. John's Wort may clash with other medications or ...

Seasonal variability of the Red Sea, from satellite gravity, radar altimetry, and in situ observations

NASA Astrophysics Data System (ADS)

Wahr, John; Smeed, David A.; Leuliette, Eric; Swenson, Sean

2014-08-01

Seasonal variations of sea surface height (SSH) and mass within the Red Sea are caused mostly by exchange of heat with the atmosphere and by flow through the strait opening into the Gulf of Aden to the south. That flow involves a net mass transfer into the Red Sea during fall and out during spring, though in summer there is an influx of cool water at intermediate depths. Thus, summer water in the south is warmer near the surface due to higher air temperatures, but cooler at intermediate depths. Summer water in the north experiences warming by air-sea exchange only. The temperature affects water density, which impacts SSH but has no effect on mass. We study this seasonal cycle by combining GRACE mass estimates, altimeter SSH measurements, and steric contributions derived from the World Ocean Atlas temperature climatology. Among our conclusions are: mass contributions are much larger than steric contributions; the mass is largest in winter, consistent with winds pushing water into the Red Sea in fall and out during spring; the steric signal is largest in summer, consistent with surface warming; and the cool, intermediate-depth water flowing into the Red Sea in spring has little impact on the steric signal, because contributions from the lowered temperature are offset by effects of decreased salinity. The results suggest that the combined use of altimeter and GRACE measurements can provide a useful alternative to in situ data for monitoring the steric signal.

Trends and interannual variability of mass and steric sea level in the Tropical Asian Seas

NASA Astrophysics Data System (ADS)

Kleinherenbrink, Marcel; Riva, Riccardo; Frederikse, Thomas; Merrifield, Mark; Wada, Yoshihide

2017-08-01

The mass and steric components of sea level changes have been separated in the Tropical Asian Seas (TAS) using a statistically optimal combination of Jason satellite altimetry, GRACE satellite gravimetry, and ocean reanalyses. Using observational uncertainties, statistically optimally weighted time series for both components have been obtained in four regions within the TAS over the period January 2005 to December 2012. The mass and steric sea level variability is regressed with the first two principal components (PC1&2) of Pacific equatorial wind stress and the Dipole Mode Index (DMI). Sea level in the South China Sea is not affected by any of the indices. Steric variability in the TAS is largest in the deep Banda and Celebes seas and is affected by both PCs and the DMI. Mass variability is largest on the continental shelves, which is primarily controlled by PC1. We argue that a water flux from the Western Tropical Pacific Ocean is the cause for mass variability in the TAS. The steric trends are about 2 mm yr-1 larger than the mass trends in the TAS. A significant part of the mass trend can be explained by the aforementioned indices and the nodal cycle. Trends obtained from fingerprints of mass redistribution are statistically equal to mass trends after subtracting the nodal cycle and the indices. Ultimately, the effect of omitting the TAS in global sea level budgets is estimated to be 0.3 mm yr-1.

The origins of the directionality of noncovalent intermolecular interactions.

PubMed

Wang, Changwei; Guan, Liangyu; Danovich, David; Shaik, Sason; Mo, Yirong

2016-01-05

The recent σ-hole concept emphasizes the contribution of electrostatic attraction to noncovalent bonds, and implies that the electrostatic force has an angular dependency. Here a set of clusters, which includes hydrogen bonding, halogen bonding, chalcogen bonding, and pnicogen bonding systems, is investigated to probe the magnitude of covalency and its contribution to the directionality in noncovalent bonding. The study is based on the block-localized wavefunction (BLW) method that decomposes the binding energy into the steric and the charge transfer (CT) (hyperconjugation) contributions. One unique feature of the BLW method is its capability to derive optimal geometries with only steric effect taken into account, while excluding the CT interaction. The results reveal that the overall steric energy exhibits angular dependency notably in halogen bonding, chalcogen bonding, and pnicogen bonding systems. Turning on the CT interactions further shortens the intermolecular distances. This bond shortening enhances the Pauli repulsion, which in turn offsets the electrostatic attraction, such that in the final sum, the contribution of the steric effect to bonding is diminished, leaving the CT to dominate the binding energy. In several other systems particularly hydrogen bonding systems, the steric effect nevertheless still plays the major role whereas the CT interaction is minor. However, in all cases, the CT exhibits strong directionality, suggesting that the linearity or near linearity of noncovalent bonds is largely governed by the charge-transfer interaction whose magnitude determines the covalency in noncovalent bonds. © 2015 Wiley Periodicals, Inc.

Possible steric control of the relative strength of chelation enhanced fluorescence for zinc(II) compared to cadmium(II): metal ion complexing properties of tris(2-quinolylmethyl)amine, a crystallographic, UV-visible, and fluorometric study.

PubMed

Williams, Neil J; Gan, Wei; Reibenspies, Joseph H; Hancock, Robert D

2009-02-16

The idea is examined that steric crowding in ligands can lead to diminution of the chelation enhanced fluorescence (CHEF) effect in complexes of the small Zn(II) ion as compared to the larger Cd(II) ion. Steric crowding is less severe for the larger ion and for the smaller Zn(II) ion leads to Zn-N bond length distortion, which allows some quenching of fluorescence by the photoinduced electron transfer (PET) mechanism. Some metal ion complexing properties of the ligand tris(2-quinolylmethyl)amine (TQA) are presented in support of the idea that more sterically efficient ligands, which lead to less M-N bond length distortion with the small Zn(II) ion, will lead to a greater CHEF effect with Zn(II) than Cd(II). The structures of [Zn(TQA)H(2)O](ClO(4))(2).1.5 H(2)O (1), ([Pb(TQA)(NO(3))(2)].C(2)H(5)OH) (2), ([Ag(TQA)(ClO(4))]) (3), and (TQA).C(2)H(5)OH (4) are reported. In 1, the Zn(II) is 5-coordinate, with four N-donors from the ligand and a water molecule making up the coordination sphere. The Zn-N bonds are all of normal length, showing that the level of steric crowding in 1 is not sufficient to cause significant Zn-N bond length distortion. This leads to the observation that, as expected, the CHEF effect in the Zn(II)/TQA complex is much stronger than that in the Cd(II)/TQA complex, in contrast to similar but more sterically crowded ligands, where the CHEF effect is stronger in the Cd(II) complex. The CHEF effect for TQA with the metal ions examined varies as Zn(II) > Cd(II) > Ni(II) > Pb(II) > Hg(II) > Cu(II). The structure of 2 shows an 8-coordinate Pb(II), with evidence of a stereochemically active lone pair, and normal Pb-N bond lengths. In 3, the Ag(I) is 5-coordinate, with four N-donors from the TQA and an oxygen from the perchlorate. The Ag(I) shows no distortion toward linear 2-coordinate geometry, and the Ag-N bonds fall slightly into the upper range for Ag-N bonds in 5-coordinate complexes. The structure of 4 shows the TQA ligand to be involved in pi-stacking between quinolyl groups from adjacent TQA molecules. Formation constants determined by UV-visible spectroscopy are reported in 0.1 M NaClO(4) at 25 degrees C for TQA with Zn(II), Cd(II), and Pb(II). When compared with other similar ligands, one sees that, as the level of steric crowding increases, the stability decreases most with the small Zn(II) ion and least with the large Pb(II) ion. This is in accordance with the idea that TQA has a moderate level of steric crowding and that steric crowding increases for TQA analogs tris(2-pyridylmethyl)amine (TPyA) < TQA < tris(6-methyl-2-pyridyl)amine (TMPyA).

VizieR Online Data Catalog: GLASS. VI. MCS J0416.1-2403 HFF imaging & spectra (Hoag+, 2016)

NASA Astrophysics Data System (ADS)

Hoag, A.; Huang, K.-H.; Treu, T.; Bradac, M.; Schmidt, K. B.; Wang, X.; Brammer, G. B.; Broussard, A.; Amorin, R.; Castellano, M.; Fontana, A.; Merlin, E.; Schrabback, T.; Trenti, M.; Vulcani, B.

2017-02-01

The Grism Lens-Amplified Survey from Space (GLASS; GO-13459, PI: Treu; Schmidt+ 2014ApJ...782L..36S; Treu+ 2015, J/ApJ/812/114) observed 10 massive galaxy clusters with the HST WFC3-IR G102 and G141 grism between 2013 December and 2015 January. Each of the clusters targeted by GLASS has deep multi-band HST imaging from the Hubble Frontier Fields (HFF) in 2014 September and/or from CLASH (ESO VIMOS large program CLASH-VLT; 186.A-0798; PI: P. Rosati; Balestra+, 2016, J/ApJS/224/33). We also use mid-IR imaging data acquired with the IRAC on board the Spitzer Space Telescope obtained by the DDT program #90258 (PI: Soifer; P. Capak+ 2016, in prep.) and #80168 (PI: Bouwens). (2 data files).

A TYPE Ia SUPERNOVA AT REDSHIFT 1.55 IN HUBBLE SPACE TELESCOPE INFRARED OBSERVATIONS FROM CANDELS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodney, Steven A.; Riess, Adam G.; Jones, David O.

2012-02-10

We report the discovery of a Type Ia supernova (SN Ia) at redshift z = 1.55 with the infrared detector of the Wide Field Camera 3 (WFC3-IR) on the Hubble Space Telescope (HST). This object was discovered in CANDELS imaging data of the Hubble Ultra Deep Field and followed as part of the CANDELS+CLASH Supernova project, comprising the SN search components from those two HST multi-cycle treasury programs. This is the highest redshift SN Ia with direct spectroscopic evidence for classification. It is also the first SN Ia at z > 1 found and followed in the infrared, providing amore » full light curve in rest-frame optical bands. The classification and redshift are securely defined from a combination of multi-band and multi-epoch photometry of the SN, ground-based spectroscopy of the host galaxy, and WFC3-IR grism spectroscopy of both the SN and host. This object is the first of a projected sample at z > 1.5 that will be discovered by the CANDELS and CLASH programs. The full CANDELS+CLASH SN Ia sample will enable unique tests for evolutionary effects that could arise due to differences in SN Ia progenitor systems as a function of redshift. This high-z sample will also allow measurement of the SN Ia rate out to z Almost-Equal-To 2, providing a complementary constraint on SN Ia progenitor models.« less

TarPmiR: a new approach for microRNA target site prediction.

PubMed

Ding, Jun; Li, Xiaoman; Hu, Haiyan

2016-09-15

The identification of microRNA (miRNA) target sites is fundamentally important for studying gene regulation. There are dozens of computational methods available for miRNA target site prediction. Despite their existence, we still cannot reliably identify miRNA target sites, partially due to our limited understanding of the characteristics of miRNA target sites. The recently published CLASH (crosslinking ligation and sequencing of hybrids) data provide an unprecedented opportunity to study the characteristics of miRNA target sites and improve miRNA target site prediction methods. Applying four different machine learning approaches to the CLASH data, we identified seven new features of miRNA target sites. Combining these new features with those commonly used by existing miRNA target prediction algorithms, we developed an approach called TarPmiR for miRNA target site prediction. Testing on two human and one mouse non-CLASH datasets, we showed that TarPmiR predicted more than 74.2% of true miRNA target sites in each dataset. Compared with three existing approaches, we demonstrated that TarPmiR is superior to these existing approaches in terms of better recall and better precision. The TarPmiR software is freely available at http://hulab.ucf.edu/research/projects/miRNA/TarPmiR/ CONTACTS: haihu@cs.ucf.edu or xiaoman@mail.ucf.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Knowledge-based grouping of modeled HLA peptide complexes.

PubMed

Kangueane, P; Sakharkar, M K; Lim, K S; Hao, H; Lin, K; Chee, R E; Kolatkar, P R

2000-05-01

Human leukocyte antigens are the most polymorphic of human genes and multiple sequence alignment shows that such polymorphisms are clustered in the functional peptide binding domains. Because of such polymorphism among the peptide binding residues, the prediction of peptides that bind to specific HLA molecules is very difficult. In recent years two different types of computer based prediction methods have been developed and both the methods have their own advantages and disadvantages. The nonavailability of allele specific binding data restricts the use of knowledge-based prediction methods for a wide range of HLA alleles. Alternatively, the modeling scheme appears to be a promising predictive tool for the selection of peptides that bind to specific HLA molecules. The scoring of the modeled HLA-peptide complexes is a major concern. The use of knowledge based rules (van der Waals clashes and solvent exposed hydrophobic residues) to distinguish binders from nonbinders is applied in the present study. The rules based on (1) number of observed atomic clashes between the modeled peptide and the HLA structure, and (2) number of solvent exposed hydrophobic residues on the modeled peptide effectively discriminate experimentally known binders from poor/nonbinders. Solved crystal complexes show no vdW Clash (vdWC) in 95% cases and no solvent exposed hydrophobic peptide residues (SEHPR) were seen in 86% cases. In our attempt to compare experimental binding data with the predicted scores by this scoring scheme, 77% of the peptides are correctly grouped as good binders with a sensitivity of 71%.

Comment on "Rabbit-Ears Hybrids, VSEPR Sterics, and Other Orbital Anachronisms": A Reply to a Criticism

ERIC Educational Resources Information Center

Hiberty, Philippe C.; Danovich, David; Shaik, Sason

2015-01-01

This commentary summarizes the authors' basic disagreements with the paper, "Rabbit-Ears, VSEPR Sterics, and Other Orbital Anachronisms," which criticizes the authors' usage of the hybrid orbitals for H[subscript 2]O in their book, "A Chemist's Guide to Valence Bond Theory" (Shaik and Hiberty, 2008). The current article shows…

LFER and CoMFA studies on optical resolution of alpha-alkyl alpha-aryloxy acetic acid methyl esters on DACH-DNB chiral stationary phase.

PubMed

Carotti, A; Altomare, C; Cellamare, S; Monforte, A; Bettoni, G; Loiodice, F; Tangari, N; Tortorella, V

1995-04-01

The HPLC resolution of a series of racemic alpha-substituted alpha-aryloxy acetic acid methyl esters I on a pi-acid N,N'-(3,5-dinitrobenzoyl)-trans-1,2-diaminocyclohexane as chiral selector was modelled by linear free energy-related (LFER) equations and comparative molecular field analysis (CoMFA). Our results indicate that the retention process mainly depends on solute lipophilicity and steric properties, whereas enantioselectivity is primarily influenced by electrostatic and steric interactions. CoMFA provided additional information with respect to the LFER study, allowed the mixing of different subsets of I and led to a quantitative 3D model of steric and electrostatic factors responsible for chiral recognition.

Prediction of Osmotic Pressure of Ionic Liquids Inside a Nanoslit by MD Simulation and Continuum Approach

NASA Astrophysics Data System (ADS)

Moon, Gi Jong; Yang, Yu Dong; Oh, Jung Min; Kang, In Seok

2017-11-01

Osmotic pressure plays an important role in the processes of charging and discharging of lithium batteries. In this work, osmotic pressure of the ionic liquids confined inside a nanoslit is calculated by using both MD simulation and continuum approach. In the case of MD simulation, an ionic liquid is modeled as singly charged spheres with a short-ranged repulsive Lennard-Jones potential. The radii of the spheres are 0.5nm, reflecting the symmetry of ion sizes for simplicity. The simulation box size is 11nm×11nm×7.5nm with 1050 ion pairs. The concentration of ionic liquid is about 1.922mol/L, and the total charge on an individual wall varies from +/-60e(7.944 μm/cm2) to +/-600e(79.44 μm/cm2) . In the case of continuum approach, we classify the problems according to the correlation length and steric factor, and considered the four separate cases: 1) zero correlation length and zero steric factor, 2) zero correlation length and non-zero steric factor, 3) non-zero correlation length and zero steric factor, and 4) non-zero correlation and non-zero steric factor. Better understanding of the osmotic pressure of ionic liquids confined inside a nanoslit can be achieved by comparing the results of MD simulation and continuum approach. This research was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIP: Ministry of Science, ICT & Future Planning) (No. 2017R1D1A1B05035211).

Rhodium Carbenoid Approach for Introduction of 4-Substituted (Z)-Pent-2-enoates into Sterically Encumbered Pyrroles and Indoles

PubMed Central

Lian, Yajing; Davies, Huw M. L.

2010-01-01

An unusual rhodium-carbenoid approach for introduction of 4-substituted (Z)-pent-2-enoates into sterically encumbered pyrroles and indoles is described. These studies show that (Z)-vinylcarbenoids have a greater tendency than (E)-vinylcarbenoids to react at the vinylogous position of the carbenoid rather than at the carbenoid center. PMID:20121078

Influence of steric hindrance on enantioseparation of Dns-amino acids and pesticides on terguride based chiral selectors in capillary electrophoresis.

PubMed

Honzátko, Ales; Cvak, Jan; Vaingátová, Silvie; Flieger, Miroslav

2005-05-01

Three urea derivatives of ergoline-based chiral selectors (CSs), differing in the size of the urea side chain, i.e. dimethyl- (CSI), diethyl- (CSII), and diisopropylurea (CSIII), were used to study the effect of steric hindrance on the enantioseparation of dansyl amino acids (Dns-AAs), pesticides, and mandelic acid under condition of capillary electrophoresis (CE) in linear polyacrylamide coated capillaries. A mixture of organic modifiers (MeOH/THF, 4:1 v/v) in a BGE consisting of 100 mM beta-alanine-acetate was used to increase the solubility of CSs up to 25 mM. The capillary was filled with CS (high UV absorption), and the inlet and outlet vials contained buffer solutions only. The best enantioseparation of Dns-AAs was achieved on CSI. Increased steric hindrance of the chiral binding site led to reduction of both enantioselectivity and resolution. The opposite pattern was observed for the separation of mandelic acid enantiomers, where the best enantioseparation and resolution was obtained with CSIII. Most of the pesticides studied reached maximum selectivity on the diethylurea ergoline derivative (CSII). Enantioseparation of fenoxaprop was found to be independent of steric hindrance.

Laser flash photolysis and CIDNP studies of steric effects on coupling rate constants of imidazolidine nitroxide with carbon-centered radicals, methyl isobutyrate-2-yl and tert-butyl propionate-2-yl.

PubMed

Zubenko, Dmitry; Tsentalovich, Yuri; Lebedeva, Nataly; Kirilyuk, Igor; Roshchupkina, Galina; Zhurko, Irina; Reznikov, Vladimir; Marque, Sylvain R A; Bagryanskaya, Elena

2006-08-04

Time-resolved chemically induced dynamic nuclear polarization (TR-CIDNP) and laser flash photolysis (LFP) techniques have been used to measure rate constants for coupling between acrylate-type radicals and a series of newly synthesized stable imidazolidine N-oxyl radicals. The carbon-centered radicals under investigation were generated by photolysis of their corresponding ketone precursors RC(O)R (R = C(CH3)2-C(O)OCH3 and CH(CH3)-C(O)-OtBu) in the presence of stable nitroxides. The coupling rate constants kc for modeling studies of nitroxide-mediated polymerization (NMP) experiments were determined, and the influence of steric and electronic factors on kc values was addressed by using a Hammett linear free energy relationship. The systematic changes in kc due to the varied steric (Es,n) and electronic (sigmaL,n) characters of the substituents are well-described by the biparameter equation log(kc/M- 1s(-1)) = 3.52sigmaL,n + 0.47Es,n + 10.62. Hence, kc decreases with the increasing steric demand and increases with the increasing electron-withdrawing character of the substituents on the nitroxide.

Clash of the particle people

NASA Astrophysics Data System (ADS)

Hesketh, Gavin

2017-06-01

Particle physicist Tommaso Dorigo's book Anomaly!: Collider Physics and the Quest for New Phenomena at Fermilab takes us back to the 1990s, and covers the first 10 years of the CDF exeriment, one of two detectors on the Tevatron.

Evaluation of auto incident recording system (AIRS).

DOT National Transportation Integrated Search

2005-05-01

The Auto Incident Recording System (AIRS) is a sound-actuated video recording system. It automatically records potential incidents when activated by sound (horns, clashing metal, squealing tires, etc.). The purpose is to detect patterns of crashes at...

CLUMP-3D: Testing ΛCDM with Galaxy Cluster Shapes

NASA Astrophysics Data System (ADS)

Sereno, Mauro; Umetsu, Keiichi; Ettori, Stefano; Sayers, Jack; Chiu, I.-Non; Meneghetti, Massimo; Vega-Ferrero, Jesús; Zitrin, Adi

2018-06-01

The ΛCDM model of structure formation makes strong predictions on the concentration and shape of dark matter (DM) halos, which are determined by mass accretion processes. Comparison between predicted shapes and observations provides a geometric test of the ΛCDM model. Accurate and precise measurements needs a full three-dimensional (3D) analysis of the cluster mass distribution. We accomplish this with a multi-probe 3D analysis of the X-ray regular Cluster Lensing and Supernova survey with Hubble (CLASH) clusters combining strong and weak lensing, X-ray photometry and spectroscopy, and the Sunyaev–Zel’dovich effect (SZe). The cluster shapes and concentrations are consistent with ΛCDM predictions. The CLASH clusters are randomly oriented, as expected given the sample selection criteria. Shapes agree with numerical results for DM-only halos, which hints at baryonic physics being less effective in making halos rounder.

Condom social marketing, Pentecostalism, and structural adjustment in Mozambique: a clash of AIDS prevention messages.

PubMed

Pfeiffer, James

2004-03-01

Despite significant debate about the efficacy, ideology, and ethics of the method, condom social marketing (CSM) has become the dominant approach to AIDS education in many sub-Saharan African countries. However, critics have charged that social marketing (SM) distracts from the structural determinants of health-related behavior and excludes genuine community participation. This article argues that the diffusion of SM techniques in Africa is not driven by demonstrated efficacy but is attributable to the promotion of privatization and free markets in the structural adjustment era across the region. The CSM experience in a central Mozambican community reveals the dangers of using the method at the expense of community dialogue and participation to confront the AIDS epidemic. The advertising campaign developed to sell condoms has clashed with Pentecostal and Independent Churches, now a majority of the population, that have expanded rapidly across the region spreading a contrasting message about sexuality and risky behavior.

Special relativity in a discrete quantum universe

NASA Astrophysics Data System (ADS)

Bisio, Alessandro; D'Ariano, Giacomo Mauro; Perinotti, Paolo

2016-10-01

The hypothesis of a discrete fabric of the universe, the "Planck scale," is always on stage since it solves mathematical and conceptual problems in the infinitely small. However, it clashes with special relativity, which is designed for the continuum. Here, we show how the clash can be overcome within a discrete quantum theory where the evolution of fields is described by a quantum cellular automaton. The reconciliation is achieved by defining the change of observer as a change of representation of the dynamics, without any reference to space-time. We use the relativity principle, i.e., the invariance of dynamics under change of inertial observer, to identify a change of inertial frame with a symmetry of the dynamics. We consider the full group of such symmetries, and recover the usual Lorentz group in the relativistic regime of low energies, while at the Planck scale the covariance is nonlinearly distorted.

A Journey into AlaskaWhen I went to Alaska to study humans in nature, I wrote a story to summarize my research. It follows Caleb as he goes through Alaskan wilderness. He contrasts the peaceful ways of the Tlingit. His materialistic motives clash with others. The story ends with him dying in the wild. Caleb symbolizes unrightfully using natural resources.

NASA Astrophysics Data System (ADS)

Hosseini, A.

2017-12-01

When I went to Alaska to study humanity's place in nature, I crafted a short piece of writing as a way to summarize what I learned. The story follows the path of Caleb as he goes through the Alaskan wilderness. His actions contrast heavily with the peaceful ways of Alaska's natives, the Tlingit, and his selfish, materialistic motives clash with those of others he meets. The story ends with him dying alone, succumbing to Mother Nature's defeat. Caleb represents those who utilize natural resources at their own gain, and his journey shows the same trap many others have fallen into.

Influence of ion sterics on diffusiophoresis and electrophoresis in concentrated electrolytes

NASA Astrophysics Data System (ADS)

Stout, Robert F.; Khair, Aditya S.

2017-01-01

We quantify the diffusiophoresis and electrophoresis of a uniformly charged, spherical colloid in a binary electrolyte using modified Poisson-Nernst-Planck equations that account for steric repulsion between finite sized ions. Specifically, we utilize the Bikerman (Bik) lattice gas model and the Carnahan-Starling (CS) and Boublik-Mansoori-Carnahan-Starling-Leland (BMCSL) equations of state for monodisperse and polydisperse, respectively, hard spheres. We compute the phoretic mobility for weak applied fields using an asymptotic approach for thin diffuse layers, where ion steric effects are expected to be most prevalent. The thin diffuse layer limit requires λD/R →0 , where λD is the Debye screening length and R is the particle radius; this limit is readily attained for micron-sized colloids in concentrated electrolytic solutions. It is well known that the classic Poisson-Boltzmann (PB) model for pointlike, noninteracting ions leads to a prediction of a maximum in both the diffusiophoretic and electrophoretic mobilities with increasing particle zeta potential (at fixed λD/R ). In contrast, we find that ion sterics essentially eliminate this maximum (for reasonably attainable zeta potentials) and increase the mobility relative to PB. Next, we consider the more experimentally relevant case of a particle with a constant surface charge density and vary the electrolyte concentration, neglecting charge regulation on surface active sites. Rather surprisingly, there is little difference between the predictions of the four models (PB, Bik, CS, and BMCSL) for electrophoretic mobility in concentrated solutions, at reasonable surface charge densities (˜1 -10 μ C /cm2 ). This is because as the concentration increases, the zeta potential is reduced (to below the thermal voltage for concentrations above about 1 M) and therefore the diffuse layer structure is largely unaffected by ion sterics. For gradients of symmetric electrolytes (equal diffusivities, charge, and size) diffusiophoresis is also essentially unaffected by ion sterics, with a mobility that approaches zero with increasing concentration, just as in electrophoresis. For gradients of asymmetric electrolytes, the difference in diffusivities of the cation and anions leads to an induced electric field that acts on the charged particle. Importantly, we show that ion sterics leads to an excess contribution to the induced electric field, which increases rapidly with concentration. This increase overwhelms the accompanying decrease in zeta potential. The result is the diffusiophoretic mobility increases with concentration, rather than approaching zero. Therefore, diffusiophoresis could be an appealing alternative transport mechanism to electrophoresis in concentrated electrolyte solutions.

Fourfold Diels-Alder reaction of tetraethynylsilane.

PubMed

Geyer, Florian L; Rode, Alexander; Bunz, Uwe H F

2014-12-08

A series of ethynylated silanes, including tetraethynylsilane, was treated with tetraphenylcyclopentadienone at 300 °C under microwave irradiation to give the aromatized Diels-Alder adducts as sterically encumbered mini-dendrimers with up to 20 benzene rings. The sterically most congested adducts display red-shifted emission through intramolecular π-π interactions in the excited state. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

JVLA 1.5 GHz Continuum Observation of CLASH Clusters. I. Radio Properties of the BCGs

NASA Astrophysics Data System (ADS)

Yu, Heng; Tozzi, Paolo; van Weeren, Reinout; Liuzzo, Elisabetta; Giovannini, Gabriele; Donahue, Megan; Balestra, Italo; Rosati, Piero; Aravena, Manuel

2018-02-01

We present high-resolution (∼1″), 1.5 GHz continuum observations of the brightest cluster galaxies (BCGs) of 13 CLASH (Cluster Lensing And Supernova survey with Hubble) clusters at 0.18< z< 0.69 with the Karl G. Jansky Very Large Array (JVLA). Radio emission is clearly detected and characterized for 11 BCGs, while for two of them we obtain only upper limits to their radio flux (< 0.1 mJy at 5σ confidence level). We also consider five additional clusters whose BCG is detected in FIRST or NVSS. We find radio powers in the range from 2× {10}23 to ∼ {10}26 {{W}} {{Hz}}-1 and radio spectral indices {α }1.530 (defined as the slope between 1.5 and 30 GHz) distributed from ∼ -1 to ‑0.25 around the central value < α > =-0.68. The radio emission from the BCGs is resolved in three cases (Abell 383, MACS J1931, and RX J2129), and unresolved or marginally resolved in the remaining eight cases observed with JVLA. In all the cases the BCGs are consistent with being powered by active galactic nuclei. The radio power shows a positive correlation with the BCG star formation rate, and a negative correlation with the central entropy of the surrounding intracluster medium (ICM) except in two cases (MACS J1206 and CL J1226). Finally, over the restricted range in radio power sampled by the CLASH BCGs, we observe a significant scatter between the radio power and the average mechanical power stored in the ICM cavities.

Intramolecular energies of the cytotoxic protein CagA of Helicobacter pylori as a possible descriptor of strains' pathogenicity level.

PubMed

Rojas-Rengifo, Diana F; Alvarez-Silva, Maria Camila; Ulloa-Guerrero, Cindy P; Nuñez-Velez, Vanessa Lucía; Del Pilar Delgado, Maria; Aguilera, Sonia Milena; Castro, Harold; Jaramillo, Carlos Alberto; Fernando González Barrios, Andrés

2018-05-25

The Helicobacter pylori cytotoxin-associated gene A (CagA) is known for causing gastroduodenal diseases, such as atrophic gastritis and peptic ulcerations. Furthermore Helicobacter pylori CagA positive strains has been reported as one of the main risk factors for gastric cancer (Parsonnet et al., 1997). Structural variations in the CagA structure can alter its affinity with the host proteins, inducing differences in the pathogenicity of H. pylori. CagA N-terminal region is characterized for be conserved among all H. pylori strains since the C-terminal region is characterized by an intrinsically disorder behavior. We generated complete structural models of CagA using different conformations of the C-terminal region for two H. pylori strains. These models contain the same EPIYA (ABC 1 C 2 ) motifs but different level of pathogenicity: gastric cancer and duodenal ulcer. Using these structural models we evaluated the pathogenicity level of the H. pylori strain, based on the affinity of the interaction with SHP-2 and Grb2 receptors and on the number of interactions with the EPIYA motif. We found that the main differences in the interaction was due to the contributions of certain types of energies from each strain and not from the total energy of the molecule. Specifically, the electrostatic energy, helix dipole energy, Wander Waals clashes, torsional clash, backbone clash and cis bond energy allowed a separation between severe and mild pathology for the interaction of only CagA with SHP2. Copyright © 2018 Elsevier Ltd. All rights reserved.

A clash of civilizations? Examining liberal-democratic values in Turkey and the European Union.

PubMed

Dixon, Jeffrey C

2008-12-01

Turkey's proposed entry into the European Union (EU) has been undermined by Europeans' perceptions of Turkish-European cultural differences, particularly regarding the liberal-democratic values that the EU promotes (democracy, rule of law, and respect for and appreciation of minority/human rights). Yet, cross-national research on values has not focused on Turkey, the EU, and these liberal-democratic values, leaving assumptions of cultural differences and their explanations untested. Through analyses of World and European Values Survey data (1999-2002), this article asks whether people in Turkey have the same values regarding democracy, rule of law (versus religious and authoritarian rule), and minority/human rights as people in EU member and candidate states (as of 2000)? What factors explain these values? I find that people in Turkey support democracy to the same extent as people in EU member and candidate states, but people in Turkey are more supportive of religious and authoritarian rule and are less tolerant of minorities. Although the 'clash of civilizations' thesis expects liberal values to be ordered according to countries' religious traditions, with western Christian the most supportive and Islamic the least, only for tolerance of minorities values is this pattern found. Instead, economic development most consistently explains differences between Turkey and EU member and candidate states in support for these values. I conclude with calls for theoretical refinement, particularly of the clash of civilizations thesis, along with suggestions for future research to examine more Muslim and Orthodox countries; I discuss the debate over Turkey's EU entry.

Tuning main group redox chemistry through steric loading: subvalent Group 13 metal complexes of carbazolyl ligands.

PubMed

Mansaray, Hassanatu B; Kelly, Michael; Vidovic, Dragoslav; Aldridge, Simon

2011-05-02

The ability of substituted carbazol-9-yl systems to ligate in σ fashion through the amido N-donor, or to adopt alternative coordination modes through the π system of the central five-membered ring, can be tuned by systematic variation in the steric demands of substituents in the 1- and 8-positions. The differing affinities of the two modes of coordination for hard and soft metal centres can be shown to influence not only cation selectivity, but also the redox properties of the metal centre. Thus, the highly sterically sterically demanding 1,3,6,8-tetra-tert-butylcarbazolyl ligand can be used to generate the structurally characterised amido-indium(I) complex, [{(tBu(4)carb)In}(n)], (together with its isostructural thallium counterpart) in which the metal centre interacts with the central pyrrolyl ring in η(3) fashion [d(In-N)=2.679(3) Å; d(In-C)=2.819(3), 2.899(3) Å]. By contrast, the smaller 3,6-di-tert-butylcarbazolyl system is less able to restrict the metal centre from binding at the anionic nitrogen donor in the plane of the carbazolyl ligand (i.e. in σ fashion). Analogous chemistry with In(I) precursors therefore leads to disproportionation to the much harder In(II) [and In(0)], and the formation of the mixed-valence product, [In(2){In(2)(tBu(2)carb)(6)}], a homoleptic molecular [In(4)(NR(2))(6)] system. This chemistry reveals a flexibility of ligation for carbazolyl systems that contrasts markedly with that of the similarly sterically encumbered terphenyl ligand family. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Deep Ocean Warming Assessed from Altimeters, GRACE, 3 In-situ Measurements, and a Non-Boussinesq OGCM

NASA Technical Reports Server (NTRS)

Song, Y. Tony; Colberg, Frank

2011-01-01

Observational surveys have shown significant oceanic bottom water warming, but they are too spatially and temporally sporadic to quantify the deep ocean contribution to the present-day sea level rise (SLR). In this study, altimetry sea surface height (SSH), Gravity Recovery and Climate Experiment (GRACE) ocean mass, and in situ upper ocean (0-700 m) steric height have been assessed for their seasonal variability and trend maps. It is shown that neither the global mean nor the regional trends of altimetry SLR can be explained by the upper ocean steric height plus the GRACE ocean mass. A non-Boussinesq ocean general circulation model (OGCM), allowing the sea level to rise as a direct response to the heat added into the ocean, is then used to diagnose the deep ocean steric height. Constrained by sea surface temperature data and the top of atmosphere (TOA) radiation measurements, the model reproduces the observed upper ocean heat content well. Combining the modeled deep ocean steric height with observational upper ocean data gives the full depth steric height. Adding a GRACE-estimated mass trend, the data-model combination explains not only the altimetry global mean SLR but also its regional trends fairly well. The deep ocean warming is mostly prevalent in the Atlantic and Indian oceans, and along the Antarctic Circumpolar Current, suggesting a strong relation to the oceanic circulation and dynamics. Its comparison with available bottom water measurements shows reasonably good agreement, indicating that deep ocean warming below 700 m might have contributed 1.1 mm/yr to the global mean SLR or one-third of the altimeter-observed rate of 3.11 +/- 0.6 mm/yr over 1993-2008.

CLASH: Weak-lensing shear-and-magnification analysis of 20 galaxy clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Umetsu, Keiichi; Czakon, Nicole; Medezinski, Elinor

2014-11-10

We present a joint shear-and-magnification weak-lensing analysis of a sample of 16 X-ray-regular and 4 high-magnification galaxy clusters at 0.19 ≲ z ≲ 0.69 selected from the Cluster Lensing And Supernova survey with Hubble (CLASH). Our analysis uses wide-field multi-color imaging, taken primarily with Suprime-Cam on the Subaru Telescope. From a stacked-shear-only analysis of the X-ray-selected subsample, we detect the ensemble-averaged lensing signal with a total signal-to-noise ratio of ≅ 25 in the radial range of 200-3500 kpc h {sup –1}, providing integrated constraints on the halo profile shape and concentration-mass relation. The stacked tangential-shear signal is well described bymore » a family of standard density profiles predicted for dark-matter-dominated halos in gravitational equilibrium, namely, the Navarro-Frenk-White (NFW), truncated variants of NFW, and Einasto models. For the NFW model, we measure a mean concentration of c{sub 200c}=4.01{sub −0.32}{sup +0.35} at an effective halo mass of M{sub 200c}=1.34{sub −0.09}{sup +0.10}×10{sup 15} M{sub ⊙}. We show that this is in excellent agreement with Λ cold dark matter (ΛCDM) predictions when the CLASH X-ray selection function and projection effects are taken into account. The best-fit Einasto shape parameter is α{sub E}=0.191{sub −0.068}{sup +0.071}, which is consistent with the NFW-equivalent Einasto parameter of ∼0.18. We reconstruct projected mass density profiles of all CLASH clusters from a joint likelihood analysis of shear-and-magnification data and measure cluster masses at several characteristic radii assuming an NFW density profile. We also derive an ensemble-averaged total projected mass profile of the X-ray-selected subsample by stacking their individual mass profiles. The stacked total mass profile, constrained by the shear+magnification data, is shown to be consistent with our shear-based halo-model predictions, including the effects of surrounding large-scale structure as a two-halo term, establishing further consistency in the context of the ΛCDM model.« less

Steric effects in the design of Co-Schiff base complexes for the catalytic oxidation of lignin models to para-benzoquinones

Treesearch

Berenger Biannic; Joseph J. Bozell; Thomas Elder

2014-01-01

New Co-Schiff base complexes that incorporate a sterically hindered ligand and an intramolecular bulky piperazine base in close proximity to the Co center are synthesized. Their utility as catalysts for the oxidation of para-substituted lignin model phenols with molecular oxygen is examined. Syringyl and guaiacyl alcohol, as models of S and G units in lignin, are...

Affine-response model of molecular solvation of ions: Accurate predictions of asymmetric charging free energies.

PubMed

Bardhan, Jaydeep P; Jungwirth, Pavel; Makowski, Lee

2012-09-28

Two mechanisms have been proposed to drive asymmetric solvent response to a solute charge: a static potential contribution similar to the liquid-vapor potential, and a steric contribution associated with a water molecule's structure and charge distribution. In this work, we use free-energy perturbation molecular-dynamics calculations in explicit water to show that these mechanisms act in complementary regimes; the large static potential (∼44 kJ/mol/e) dominates asymmetric response for deeply buried charges, and the steric contribution dominates for charges near the solute-solvent interface. Therefore, both mechanisms must be included in order to fully account for asymmetric solvation in general. Our calculations suggest that the steric contribution leads to a remarkable deviation from the popular "linear response" model in which the reaction potential changes linearly as a function of charge. In fact, the potential varies in a piecewise-linear fashion, i.e., with different proportionality constants depending on the sign of the charge. This discrepancy is significant even when the charge is completely buried, and holds for solutes larger than single atoms. Together, these mechanisms suggest that implicit-solvent models can be improved using a combination of affine response (an offset due to the static potential) and piecewise-linear response (due to the steric contribution).

Peptide probes reveal a hydrophobic steric ratchet in the anthrax toxin protective antigen translocase

PubMed Central

Colby, Jennifer M.; Krantz, Bryan A.

2015-01-01

Anthrax toxin is a tripartite virulence factor produced by Bacillus anthracis during infection. Under acidic endosomal pH conditions, the toxin's protective antigen (PA) component forms a transmembrane channel in host cells. The PA channel then translocates its two enzyme components, lethal factor (LF) and edema factor (EF), into the host cytosol under the proton motive force (PMF). Protein translocation under a PMF is catalyzed by a series of nonspecific polypeptide binding sites, called clamps. A 10-residue guest/host peptide model system, KKKKKXXSXX, was used to functionally probe polypeptide-clamp interactions within wild-type PA channels. The guest residues were Thr, Ala, Leu, Phe, Tyr, and Trp. In steady-state translocation experiments, the channel blocked most tightly with peptides that had increasing amounts of nonpolar surface area. Cooperative peptide binding was observed in the Trp-containing peptide sequence but not the other tested sequences. Trp substitutions into a flexible, uncharged linker between LF amino-terminal domain and diphtheria toxin A chain expedited translocation. Therefore, peptide clamp sites in translocase channels can sense large steric features (like tryptophan) in peptides; and while these steric interactions may make a peptide translocate poorly, in the context of folded domains they can make the protein translocate more rapidly presumably via a hydrophobic steric ratchet mechanism. PMID:26363343

Affine-response model of molecular solvation of ions: Accurate predictions of asymmetric charging free energies

PubMed Central

Bardhan, Jaydeep P.; Jungwirth, Pavel; Makowski, Lee

2012-01-01

Two mechanisms have been proposed to drive asymmetric solvent response to a solute charge: a static potential contribution similar to the liquid-vapor potential, and a steric contribution associated with a water molecule's structure and charge distribution. In this work, we use free-energy perturbation molecular-dynamics calculations in explicit water to show that these mechanisms act in complementary regimes; the large static potential (∼44 kJ/mol/e) dominates asymmetric response for deeply buried charges, and the steric contribution dominates for charges near the solute-solvent interface. Therefore, both mechanisms must be included in order to fully account for asymmetric solvation in general. Our calculations suggest that the steric contribution leads to a remarkable deviation from the popular “linear response” model in which the reaction potential changes linearly as a function of charge. In fact, the potential varies in a piecewise-linear fashion, i.e., with different proportionality constants depending on the sign of the charge. This discrepancy is significant even when the charge is completely buried, and holds for solutes larger than single atoms. Together, these mechanisms suggest that implicit-solvent models can be improved using a combination of affine response (an offset due to the static potential) and piecewise-linear response (due to the steric contribution). PMID:23020318

Hydrological and oceanic excitations to polar motion andlength-of-day variation

NASA Astrophysics Data System (ADS)

Chen, J. L.; Wilson, C. R.; Chao, B. F.; Shum, C. K.; Tapley, B. D.

2000-04-01

Water mass redistributions in the global hydrosphere, including continental water storage change and non-steric sea level change, introduce variations in the hydrological angular momentum (HAM) and the oceanic angular momentum (OAM). Under the conservation of angular momentum, HAM and OAM variations are significant excitation sources of the Earth rotational variations at a wide range of timescales. In this paper, we estimate HAM and OAM variations and their excitations to polar motion and length-of-day variation using soil moisture and snow estimates andnon-steric sea level change determined by TOPEX/Poseidon satellite radar altimeter observations and a simplified steric sea level change model. The results are compared with the variations of polar motion and LOD that are not accounted for by the atmosphere. This study indicates that seasonal continental water storage change provides significant contributions to both polar motion and LOD variation, especially to polar motion X, and the non-steric sea level change is responsible for a major part of the remaining excitations at both seasonal scale and high frequencies, particularly in polar motion Y and LOD. The good correlation between OAM contributions and the remaining excitations shows that large-scale non-tidal mass variation exists in the oceans and can be detected by TOPEX/Poseidon altimeter observations.

Experimental verification of the steric-entropic mode of retention in centrifugal field-flow fractionation using illite clay plates.

PubMed

Tadjiki, Soheyl; Beckett, Ronald

2018-02-23

The commonly used theory to describe the normal Brownian mode of field-flow fractionation (FFF) assumes the particles to be point masses and hence the shape is ignored. Beckett and Giddings extended this theory to include the effect of thin rods and discs being forced very close to the accumulation wall. By including the decrease in the entropy this causes, they derived new expressions for the retention of such nonspherical particles in FFF. The steric-entropic theory predicts that when the sample cloud thickness is less than the major dimension of the rods or discs then particles elute earlier than predicted by the Brownian mode theory. This leads to an underestimation of the buoyant mass and equivalent spherical diameter calculated from FFF data. In this paper we report for the first time experimental data for the retention of thin illite particles in centrifugal FFF that agrees well with these steric-entropic predictions. Not only do the size distributions calculated using the Brownian mode theory shift to lower size when the field is increased but the shift in the retention ratio of the peak maxima of the FFF fractograms could be predicted fairly accurately by the steric-entropic equations. Copyright © 2018 Elsevier B.V. All rights reserved.

Protein unfolding with a steric trap.

PubMed

Blois, Tracy M; Hong, Heedeok; Kim, Tae H; Bowie, James U

2009-10-07

The study of protein folding requires a method to drive unfolding, which is typically accomplished by altering solution conditions to favor the denatured state. This has the undesirable consequence that the molecular forces responsible for configuring the polypeptide chain are also changed. It would therefore be useful to develop methods that can drive unfolding without the need for destabilizing solvent conditions. Here we introduce a new method to accomplish this goal, which we call steric trapping. In the steric trap method, the target protein is labeled with two biotin tags placed close in space so that both biotin tags can only be bound by streptavidin when the protein unfolds. Thus, binding of the second streptavidin is energetically coupled to unfolding of the target protein. Testing the method on a model protein, dihydrofolate reductase (DHFR), we find that streptavidin binding can drive unfolding and that the apparent binding affinity reports on changes in DHFR stability. Finally, by employing the slow off-rate of wild-type streptavidin, we find that DHFR can be locked in the unfolded state. The steric trap method provides a simple method for studying aspects of protein folding and stability in native solvent conditions, could be used to specifically unfold selected domains, and could be applicable to membrane proteins.

Turning Culture Clash into Collaboration.

ERIC Educational Resources Information Center

Gayle, Dennis J.; Hakim, Toufic M.; Agarwal, Vijendra K.; Alfonso, Peter J.

1999-01-01

A survey investigated college faculty and administrator attitudes on issues related to institutional governance. Results offer trustees several strategies for fostering institutional change: build on the overlap in attitudes about governance; foster dialog about teaching, research, and governance among board, faculty, and administrators; improve…

On dynamic prices: a clash of beliefs?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanser, Philip Q

2010-07-15

While insightful essays have been written regarding the moral appropriateness of dynamic pricing, they have an implicit underlying framework for determining justness and fairness that may not necessarily accord completely with the view promulgated in regard to utility rate setting generally. (author)

What's So Important about Conducting Research Involving Third Parties?

ERIC Educational Resources Information Center

Murrelle, Lenn; McCarthy, Charles R.

2001-01-01

Recent federal regulatory rulings call into question the collection of family medical history without the consent of third-party family members. The clash between privacy rights and research methods could influence the quality of genetic and epidemiological research. (SK)

Innovation: the classic traps.

PubMed

Kanter, Rosabeth Moss

2006-11-01

Never a fad, but always in or out of fashion, innovation gets rediscovered as a growth enabler every half dozen years. Too often, though, grand declarations about innovation are followed by mediocre execution that produces anemic results, and innovation groups are quietly disbanded in cost-cutting drives. Each managerial generation embarks on the same enthusiastic quest for the next new thing. And each generation faces the same vexing challenges- most of which stem from the tensions between protecting existing revenue streams critical to current success and supporting new concepts that may be crucial to future success. In this article, Harvard Business School professor Rosabeth Moss Kanter reflects on the four major waves of innovation enthusiasm she's observed over the past 25 years. She describes the classic mistakes companies make in innovation strategy, process, structure, and skills assessment, illustrating her points with a plethora of real-world examples--including AT&T Worldnet, Timberland, and Ocean Spray. A typical strategic blunder is when managers set their hurdles too high or limit the scope of their innovation efforts. Quaker Oats, for instance, was so busy in the 1990s making minor tweaks to its product formulas that it missed larger opportunities in distribution. A common process mistake is when managers strangle innovation efforts with the same rigid planning, budgeting, and reviewing approaches they use in their existing businesses--thereby discouraging people from adapting as circumstances warrant. Companies must be careful how they structure fledgling entities alongside existing ones, Kanter says, to avoid a clash of cultures and agendas--which Arrow Electronics experienced in its attempts to create an online venture. Finally, companies commonly undervalue and underinvest in the human side of innovation--for instance, promoting individuals out of innovation teams long before their efforts can pay off. Kanter offers practical advice for avoiding these traps.

Diaryl-1,2,3-Triazolylidene Platinum(II) Complexes.

PubMed

Soellner, Johannes; Strassner, Thomas

2018-04-11

Control of the excited state geometry by rational ligand design leads to a new class of phosphorescent emitters with extraordinary photophysical properties. Extension of the π-system in the triplet state leading to a significant bathochromic shift of the emission was avoided by introduction of additional steric demand. We report the synthesis, characterization and photophysical properties of novel platinum(II) complexes bearing C^C* cyclometalated mesoionic carbene (MIC) with different β-diketonate ligands. The MIC ligand precursors were prepared from 1-phenyl-1,2,3-triazole using arylation protocols, introducing phenyl or mesityl functionalities. A solid state structure confirming the NMR assignments is presented. The emission properties were investigated in detail at room temperature and 77 K and are supported by DFT calculations and cyclic voltammetry. All complexes, with emission maxima between 502-534 nm, emit with quantum efficiencies ranging from 70-84 % in PMMA films. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues

PubMed Central

Lai, Samuel K.; Wang, Ying-Ying; Hanes, Justin

2009-01-01

Mucus is a viscoelastic and adhesive gel that protects the lung airways, gastrointestinal (GI) tract, vagina, eye and other mucosal surfaces. Most foreign particulates, including conventional particle-based drug delivery systems, are efficiently trapped in human mucus layers by steric obstruction and/or adhesion. Trapped particles are typically removed from the mucosal tissue within seconds to a few hours depending on anatomical location, thereby strongly limiting the duration of sustained drug delivery locally. A number of debilitating diseases could be treated more effectively and with fewer side effects if drugs and genes could be more efficiently delivered to the underlying mucosal tissues in a controlled manner. This review first describes the tenacious mucus barrier properties that have precluded the efficient penetration of therapeutic particles. It then reviews the design and development of new mucus-penetrating particles that may avoid rapid mucus clearance mechanisms, and thereby provide targeted or sustained drug delivery for localized therapies in mucosal tissues. PMID:19133304

Ligand Effects in Aluminum Cluster based Energetic Materials

DTIC Science & Technology

2017-09-01

was recently reported and the effect of their increased steric bulk is discussed here. Experimental results and density functional theory (DFT...analysis show that these clusters are enthalpically more stable than the Cp* variant, due primarily to non -covalent interactions (NCIs) across ligand...C5Me4iPr), two clusters similar to Al4Cp*4, was recently reported and the effect of their increased steric bulk is discussed here. Experimental

13C nuclear magnetic resonance data of lanosterol derivatives—Profiling the steric topology of the steroid skeleton via substituent effects on its 13C NMR

NASA Astrophysics Data System (ADS)

Dias, Jerry Ray; Gao, Hongwu

2009-12-01

The 13C NMR spectra of over 24 tetracyclic triterpenoid derivatives have been structurally analyzed. The 13C NMR chemical shifts allow one to probe the steric topology of the rigid steroid skeleton and inductive effects of its substituents. Use of deuterium labeling in chemical shift assignment and B-ring aromatic terpenoids are also featured.

Ion-Conserving Modified Poisson-Boltzmann Theory Considering a Steric Effect in an Electrolyte

NASA Astrophysics Data System (ADS)

Sugioka, Hideyuki

2016-12-01

The modified Poisson-Nernst-Planck (MPNP) and modified Poisson-Boltzmann (MPB) equations are well known as fundamental equations that consider a steric effect, which prevents unphysical ion concentrations. However, it is unclear whether they are equivalent or not. To clarify this problem, we propose an improved free energy formulation that considers a steric limit with an ion-conserving condition and successfully derive the ion-conserving modified Poisson-Boltzmann (IC-MPB) equations that are equivalent to the MPNP equations. Furthermore, we numerically examine the equivalence by comparing between the IC-MPB solutions obtained by the Newton method and the steady MPNP solutions obtained by the finite-element finite-volume method. A surprising aspect of our finding is that the MPB solutions are much different from the MPNP (IC-MPB) solutions in a confined space. We consider that our findings will significantly contribute to understanding the surface science between solids and liquids.

The helical structure of DNA facilitates binding

NASA Astrophysics Data System (ADS)

Berg, Otto G.; Mahmutovic, Anel; Marklund, Emil; Elf, Johan

2016-09-01

The helical structure of DNA imposes constraints on the rate of diffusion-limited protein binding. Here we solve the reaction-diffusion equations for DNA-like geometries and extend with simulations when necessary. We find that the helical structure can make binding to the DNA more than twice as fast compared to a case where DNA would be reactive only along one side. We also find that this rate advantage remains when the contributions from steric constraints and rotational diffusion of the DNA-binding protein are included. Furthermore, we find that the association rate is insensitive to changes in the steric constraints on the DNA in the helix geometry, while it is much more dependent on the steric constraints on the DNA-binding protein. We conclude that the helical structure of DNA facilitates the nonspecific binding of transcription factors and structural DNA-binding proteins in general.

Brownian dynamics of sterically-stabilized colloidal suspensions

DOE Office of Scientific and Technical Information (OSTI.GOV)

TeGrotenhuis, W.E.; Radke, C.J.; Denn, M.M.

1994-02-01

One application where microstructure plays a critical role is in the production of specialty ceramics, where colloidal suspensions act as precursors; here the microstructure influences the structural, thermal, optical and electrical properties of the ceramic products. Using Brownian dynamics, equilibrium and dynamic properties are calculated for colloidal suspensions that are stabilized through the Milner, Witten and Cates (1988) steric potential. Results are reported for osmotic pressures, radial distributions functions, static structure factors, and self-diffusion coefficients. The sterically-stabilized systems are also approximated by equivalent hard spheres, with good agreement for osmotic pressure and long-range structure. The suitability of the potential tomore » model the behavior of a real system is explored by comparing static structure factors calculated from Brownian dynamics simulations to those measured using SANS. Finally, the effects of Hamaker and hydrodynamic forces on calculated properties are investigated.« less

The epidemiology and type of injuries seen at the accident and emergency unit of a Nigerian referral center

PubMed Central

Adoga, Adeyi A.; Ozoilo, Kenneth N.

2014-01-01

Background: A plethora of injuries present at any accident and emergency unit, but the pattern of the injuries varies from region to region especially in ours with the increased ethno-religious clashes and terrorist attacks. This study aims to determine the epidemiology and type of injuries presenting to our center with the possibility of developing injury surveillance initiatives in our center and Nigeria as a whole. Materials and Methods: Injured patients consecutively presenting to the accident and emergency department of the Jos University Teaching Hospital within the period February 2011 to January 2012 were prospectively recorded. Results: A total of 720 injured patients admitted with an age range of 8 months to 75 years (mean = 37.9; SD = ±52.4), which consists of 544 males and 176 females giving a male to female ratio of 3.1:1. Patients aged 20-29 years were in the majority (n = 220, 30.6%) with peak incidences in the period of communal clashes. Injuries sustained from motorcycles were the highest (n = 248, 34.4%). Others were 160 (22.2%) in other vehicular and pedestrian injuries, machete (n = 128), gunshots (n = 92), burns (n = 36), bomb blast injuries (n = 16), fall from heights (n = 32) and miscellaneous (n = 8). Injuries sustained in communal clashes and terrorist attacks accounted for 236 (32.8%) presentations. The most common site of injury was the head (n = 30 4, 42.2%). Relatives, passersby and law enforcement agencies brought patients to the hospital with times between injury and presentation ranging from 1 h to 3 weeks. 40 (5.6%) patients were brought in dead. Conclusion: A collective effort - on the part of the government and the citizenry is required to ensure better outcomes and a safer society for all. PMID:24812451

STAR FORMATION ACTIVITY IN CLASH BRIGHTEST CLUSTER GALAXIES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fogarty, Kevin; Postman, Marc; Connor, Thomas

2015-11-10

The CLASH X-ray selected sample of 20 galaxy clusters contains 10 brightest cluster galaxies (BCGs) that exhibit significant (>5σ) extinction-corrected star formation rates (SFRs). Star formation activity is inferred from photometric estimates of UV and Hα+[N ii] emission in knots and filaments detected in CLASH Hubble Space Telescope ACS and WFC3 observations. UV-derived SFRs in these BCGs span two orders of magnitude, including two with a SFR ≳ 100 M{sub ⊙} yr{sup −1}. These measurements are supplemented with [O ii], [O iii], and Hβ fluxes measured from spectra obtained with the SOAR telescope. We confirm that photoionization from ongoing starmore » formation powers the line emission nebulae in these BCGs, although in many BCGs there is also evidence of a LINER-like contribution to the line emission. Coupling these data with Chandra X-ray measurements, we infer that the star formation occurs exclusively in low-entropy cluster cores and exhibits a correlation with gas properties related to cooling. We also perform an in-depth study of the starburst history of the BCG in the cluster RXJ1532.9+3021, and create 2D maps of stellar properties on scales down to ∼350 pc. These maps reveal evidence for an ongoing burst occurring in elongated filaments, generally on ∼0.5–1.0 Gyr timescales, although some filaments are consistent with much younger (≲100 Myr) burst timescales and may be correlated with recent activity from the active galactic nucleus. The relationship between BCG SFRs and the surrounding intracluster medium gas properties provide new support for the process of feedback-regulated cooling in galaxy clusters and is consistent with recent theoretical predictions.« less

CLASH: NEW MULTIPLE IMAGES CONSTRAINING THE INNER MASS PROFILE OF MACS J1206.2-0847

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zitrin, A.; Rosati, P.; Nonino, M.

2012-04-20

We present a strong-lensing analysis of the galaxy cluster MACS J1206.2-0847 (z = 0.44) using UV, Optical, and IR, HST/ACS/WFC3 data taken as part of the CLASH multi-cycle treasury program, with VLT/VIMOS spectroscopy for some of the multiply lensed arcs. The CLASH observations, combined with our mass model, allow us to identify 47 new multiply lensed images of 12 distant sources. These images, along with the previously known arc, span the redshift range 1 {approx}< z {approx}< 5.5, and thus enable us to derive a detailed mass distribution and to accurately constrain, for the first time, the inner mass profilemore » of this cluster. We find an inner profile slope of dlog {Sigma}/dlog {theta} {approx_equal} -0.55 {+-} 0.1 (in the range [1'', 53''], or 5 kpc {approx}< r {approx}< 300 kpc), as commonly found for relaxed and well-concentrated clusters. Using the many systems uncovered here we derive credible critical curves and Einstein radii for different source redshifts. For a source at z{sub s} {approx_equal} 2.5, the critical curve encloses a large area with an effective Einstein radius of {theta}{sub E} = 28'' {+-} 3'', and a projected mass of (1.34 {+-} 0.15) Multiplication-Sign 10{sup 14} M{sub Sun }. From the current understanding of structure formation in concordance cosmology, these values are relatively high for clusters at z {approx} 0.5, so that detailed studies of the inner mass distribution of clusters such as MACS J1206.2-0847 can provide stringent tests of the {Lambda}CDM paradigm.« less

Steric Effect on the Nucleophilic Reactivity of Nickel(III) Peroxo Complexes.

PubMed

Kim, Jalee; Shin, Bongki; Kim, Hyunjeong; Lee, Junhyung; Kang, Joongoo; Yanagisawa, Sachiko; Ogura, Takashi; Masuda, Hideki; Ozawa, Tomohiro; Cho, Jaeheung

2015-07-06

A set of nickel(III) peroxo complexes bearing tetraazamacrocyclic ligands, [Ni(III)(TBDAP)(O2)](+) (TBDAP = N,N'-di-tert-butyl-2,11-diaza[3.3](2,6)pyridinophane) and [Ni(III)(CHDAP)(O2)](+) (CHDAP = N,N'-dicyclohexyl-2,11-diaza[3.3](2,6)pyridinophane), were prepared by reacting [Ni(II)(TBDAP)(NO3)(H2O)](+) and [Ni(II)(CHDAP)(NO3)](+), respectively, with H2O2 in the presence of triethylamine. The mononuclear nickel(III) peroxo complexes were fully characterized by various physicochemical methods, such as UV-vis, electrospray ionization mass spectrometry, resonance Raman, electron paramagnetic resonance, and X-ray analysis. The spectroscopic and structural characterization clearly shows that the NiO2 cores are almost identical where the peroxo ligand is bound in a side-on fashion. However, the different steric properties of the supporting ligands were confirmed by X-ray crystallography, where the CHDAP ligand gives enough space around the Ni core compared to the TBDAP ligand. The nickel(III) peroxo complexes showed reactivity in the oxidation of aldehydes. In the aldehyde deformylation reaction, the nucleophilic reactivity of the nickel(III) peroxo complexes was highly dependent on the steric properties of the macrocyclic ligands, with a reactivity order of [Ni(III)(TBDAP)(O2)](+) < [Ni(III)(CHDAP)(O2)](+). This result provides fundamental insight into the mechanism of the structure (steric)-reactivity relationship of metal peroxo intermediates.

Effect of Pendant Side-Chain Sterics and Dipole Forces on Short Range Ordering in Random Polyelectrolytes

NASA Astrophysics Data System (ADS)

Nwosu, Chinomso; Pandey, Tara; Herring, Andrew; Coughlin, Edward; University of Massachusetts, Amherst Collaboration; Colorado School of Mines Collaboration

Backbone-to-backbone spacing in polymers is known to be dictated by the length of the pendant side-chains. Dipole forces in random polyelectrolytes lead to ionic clusters with a characteristic spacing that can be observed by SAXS. Repulsion due to side-chain sterics will compete with dipole forces driving cluster formation in random polyelectrolytes. A model study on short range order in anion exchange membranes (AEMs) of quaternized P4VP-ran-PI is presented. Quaternization of P4VP with alkyl bromides having different numbers of carbons, CnBr, introduces pendant side-chains as well as charges. X-ray scattering performed on PQ4VP-ran-PI(CnBr) show that when n <5 the dipole forces dominate leading to the formation of ionic clusters. However, when n >4, the chains remain separated due to sterics, forming a distinct backbone-to-backbone spacing morphology. For n=3, both dipole clustering and backbone spacing can coexist. Crosslinking of the isoprene units increased the coexistence window from n=3 to n=6. Impedance measurements show that a maximum conductivity of 110mS/cm was obtained for PQ4VP-ran-PI(C3Br). A discussion on short range order due to competition, or counter balancing, of steric repulsion and dipole forces will be presented. US Army MURI project (W911NF1010520).

Steric interactions determine side-chain conformations in protein cores.

PubMed

Caballero, D; Virrueta, A; O'Hern, C S; Regan, L

2016-09-01

We investigate the role of steric interactions in defining side-chain conformations in protein cores. Previously, we explored the strengths and limitations of hard-sphere dipeptide models in defining sterically allowed side-chain conformations and recapitulating key features of the side-chain dihedral angle distributions observed in high-resolution protein structures. Here, we show that modeling residues in the context of a particular protein environment, with both intra- and inter-residue steric interactions, is sufficient to specify which of the allowed side-chain conformations is adopted. This model predicts 97% of the side-chain conformations of Leu, Ile, Val, Phe, Tyr, Trp and Thr core residues to within 20°. Although the hard-sphere dipeptide model predicts the observed side-chain dihedral angle distributions for both Thr and Ser, the model including the protein environment predicts side-chain conformations to within 20° for only 60% of core Ser residues. Thus, this approach can identify the amino acids for which hard-sphere interactions alone are sufficient and those for which additional interactions are necessary to accurately predict side-chain conformations in protein cores. We also show that our approach can predict alternate side-chain conformations of core residues, which are supported by the observed electron density. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Peptide Probes Reveal a Hydrophobic Steric Ratchet in the Anthrax Toxin Protective Antigen Translocase.

PubMed

Colby, Jennifer M; Krantz, Bryan A

2015-11-06

Anthrax toxin is a tripartite virulence factor produced by Bacillus anthracis during infection. Under acidic endosomal pH conditions, the toxin's protective antigen (PA) component forms a transmembrane channel in host cells. The PA channel then translocates its two enzyme components, lethal factor and edema factor, into the host cytosol under the proton motive force. Protein translocation under a proton motive force is catalyzed by a series of nonspecific polypeptide binding sites, called clamps. A 10-residue guest/host peptide model system, KKKKKXXSXX, was used to functionally probe polypeptide-clamp interactions within wild-type PA channels. The guest residues were Thr, Ala, Leu, Phe, Tyr, and Trp. In steady-state translocation experiments, the channel blocked most tightly with peptides that had increasing amounts of nonpolar surface area. Cooperative peptide binding was observed in the Trp-containing peptide sequence but not the other tested sequences. Trp substitutions into a flexible, uncharged linker between the lethal factor amino-terminal domain and diphtheria toxin A chain expedited translocation. Therefore, peptide-clamp sites in translocase channels can sense large steric features (like tryptophan) in peptides, and while these steric interactions may make a peptide translocate poorly, in the context of folded domains, they can make the protein translocate more rapidly presumably via a hydrophobic steric ratchet mechanism. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Building a Three-Dimensional Nano-Bio Interface for Aptasensing: An Analytical Methodology Based on Steric Hindrance Initiated Signal Amplification Effect.

PubMed

Du, Xiaojiao; Jiang, Ding; Hao, Nan; Qian, Jing; Dai, Liming; Zhou, Lei; Hu, Jianping; Wang, Kun

2016-10-04

The development of novel detection methodologies in electrochemiluminescence (ECL) aptasensor fields with simplicity and ultrasensitivity is essential for constructing biosensing architectures. Herein, a facile, specific, and sensitive methodology was developed unprecedentedly for quantitative detection of microcystin-LR (MC-LR) based on three-dimensional boron and nitrogen codoped graphene hydrogels (BN-GHs) assisted steric hindrance amplifying effect between the aptamer and target analytes. The recognition reaction was monitored by quartz crystal microbalance (QCM) to validate the possible steric hindrance effect. First, the BN-GHs were synthesized via self-assembled hydrothermal method and then applied as the Ru(bpy) 3 2+ immobilization platform for further loading the biomolecule aptamers due to their nanoporous structure and large specific surface area. Interestingly, we discovered for the first time that, without the aid of conventional double-stranded DNA configuration, such three-dimensional nanomaterials can directly amplify the steric hindrance effect between the aptamer and target analytes to a detectable level, and this facile methodology could be for an exquisite assay. With the MC-LR as a model, this novel ECL biosensor showed a high sensitivity and a wide linear range. This strategy supplies a simple and versatile platform for specific and sensitive determination of a wide range of aptamer-related targets, implying that three-dimensional nanomaterials would play a crucial role in engineering and developing novel detection methodologies for ECL aptasensing fields.

A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs.

PubMed

Lu, Mingjian; Kinchen, Jason M; Rossman, Kent L; Grimsley, Cynthia; Hall, Matthew; Sondek, John; Hengartner, Michael O; Yajnik, Vijay; Ravichandran, Kodi S

2005-02-22

CDM (CED-5, Dock180, Myoblast city) family members have been recently identified as novel, evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases . They regulate multiple processes, including embryonic development, cell migration, apoptotic-cell engulfment, tumor invasion, and HIV-1 infection, in diverse model systems . However, the mechanism(s) of regulation of CDM proteins has not been well understood. Here, our studies on the prototype member Dock180 reveal a steric-inhibition model for regulating the Dock180 family of GEFs. At basal state, the N-terminal SH3 domain of Dock180 binds to the distant catalytic Docker domain and negatively regulates the function of Dock180. Further studies revealed that the SH3:Docker interaction sterically blocks Rac access to the Docker domain. Interestingly, ELMO binding to the SH3 domain of Dock180 disrupted the SH3:Docker interaction, facilitated Rac access to the Docker domain, and contributed to the GEF activity of the Dock180/ELMO complex. Additional genetic rescue studies in C. elegans suggested that the regulation of the Docker-domain-mediated GEF activity by the SH3 domain and its adjoining region is evolutionarily conserved. This steric-inhibition model may be a general mechanism for regulating multiple SH3-domain-containing Dock180 family members and may have implications for a variety of biological processes.

Populism and Feminism: Odd Bedfellows.

PubMed

Kroes, Rob

2018-01-01

In this era of populist insurgency breaking the mold of democratic politics, two movements clashed.They represented opposite sides of the political spectrum, one emancipatory, the other exclusionary. One may be identified as feminism, the other as populism. This essay analyzes both concepts and explores their connection.

On Models of the University in Today's Russia

ERIC Educational Resources Information Center

Rozov, N. S.

2008-01-01

In current discussions of the problems that affect the development of higher education in Russia, two dimensions dominate, in which opinions diverge and positions clash. In the "first" ("the political and economic" dimension) the extreme poles are the "liberal approach" (according to which higher educational…

Animating Grassroots Development: Women's Popular Education in Bolivia.

ERIC Educational Resources Information Center

Healy, Kevin

1991-01-01

Describes Capacitacion Integral de la Mujer Campesina (CIMCA) development efforts within Bolivian farm communities. Describes CIMCA's focus on social change, ethnic empowerment, and women's rights. Describes organization's initial clashes with rural culture. Describes use of rotafolio drawings to spark workshop discussions, to improve women's…

When Generations Collide

ERIC Educational Resources Information Center

Fogg, Piper

2008-01-01

When four generations converge in the academic workplace, it can create serious culture clashes. It is happening across college campuses--in offices as diverse as admissions, student affairs, legal affairs, and technology. It is especially striking in the faculty ranks, where generational challenges have extra significance amid recruiting efforts,…

How to Teach Engineering and Industrial Design: a U.K. Experience.

ERIC Educational Resources Information Center

Sheldon, D. F.

1988-01-01

Explored are the possibilities of teaching engineering through a project approach. Discussed are the introduction, clashing cultures of industrial and engineering design, skills required of a designer, teaching approach to the total design activity, CAD/CAM experiences, and conclusions. (Author/YP)

More Than a Mascot.

ERIC Educational Resources Information Center

Riede, Paul

2001-01-01

Describes how several school districts have coped with protracted and contentious community debate over the retirement of high school Native American team names and mascots, when Native American sensibilities clash with high school rituals and traditions. Offers tips on how to deal with the Native American mascot issue. (PKP)

Supervising the Extended Practicum: A Contextual Approach. Monograph No. 4.

ERIC Educational Resources Information Center

Ralph, Edwin G.

Conflicts or disagreements between student teachers and university supervisors in the Extended Practicum program, College of Education, University of Saskatchewan, are often attributed to factors such as "personality clash," laziness, stubbornness, authoritarianism, prejudice, stereotyping, dogmatism, or malice. In reality, many of these…

Effect of noise spectra and a listening task upon passenger annoyance in a helicopter interior noise environment

NASA Technical Reports Server (NTRS)

Clevenson, S. A.; Leatherwood, J. D.

1979-01-01

The effects of helicopter interior noise on passenger annoyance were studied. Both reverie and listening situations were studied as well as the relative effectiveness of several descriptors (i.e., overall sound pressure level, A-weighted sound pressure level, and speech interference level) for quantifying annoyance response for these situations. The noise stimuli were based upon recordings of the interior noise of a civil helicopter research aircraft. These noises were presented at levels ranging from approximately 68 to 86 dB(A) with various gear clash tones selectively attenuated to give a range of spectra. Results indicated that annoyance during a listening condition is generally higher than annoyance during a reverie condition for corresponding interior noise environments. Attenuation of the planetary gear clash tone results in increases in listening performance but has negligible effect upon annoyance for a given noise level. The noise descriptor most effective for estimating annoyance response under conditions of reverie and listening situations is shown to be the A-weighted sound pressure level.

Not quite dead: why Egyptian doctors refuse the diagnosis of death by neurological criteria.

PubMed

Hamdy, Sherine

2013-04-01

Drawing on two years of ethnographic fieldwork in Egypt focused on organ transplantation, this paper examines the ways in which the "scientific" criteria of determining death in terms of brain function are contested by Egyptian doctors. Whereas in North American medical practice, the death of the "person" is associated with the cessation of brain function, in Egypt, any sign of biological life is evidence of the persistence, even if fleeting, of the soul. I argue that this difference does not exemplify an irresolvable culture clash but points to an unsettling aspect of cadaveric organ procurement that has emerged wherever organ transplantation is practiced. Further, I argue that a misdiagnosis of the problem, as one about "religious extremism" or a "civilizational clash," has obfuscated unresolved concerns about fairness, access, and justice within Egyptian medical spheres. This misdiagnosis has led to the suspension of a cadaveric procurement program for over 30 years, despite Egypt's pioneering efforts in kidney transplantation.

The clash of Gods: changes in a patient's use of God representations.

PubMed

Lamothe, Ryan

2009-01-01

In this article, I argue that manifest and latent intrapsychic and interpersonal clashes of god representations, which are inextricably yoked to transference and countertransference communications, signify the patient's and therapist's personal realities and histories. More specifically, the therapist's conscious (relatively speaking) commitment to a god representation will not only shape his/her analytic attitude-as well as interpretations and noninterpretive interventions-it may also be implicated in a patient altering his/her use of god representations. I suggest further that one way to understand the process of psychoanalytic therapy is how both analyst and analysand tacitly face and answer the following questions: What God(s) orients my life and relationships? What God(s) represents subjugation, fear, and the loss of freedom? What God(s) have I repressed? What God(s) represents the possibility and experience of being alive and real with others? In the end, what God(s) will I choose to serve, to surrender to?

Revisiting the contemporary sea-level budget on global and regional scales

PubMed Central

Brunnabend, Sandra-Esther; Kusche, Jürgen; Schröter, Jens; Dahle, Christoph

2016-01-01

Dividing the sea-level budget into contributions from ice sheets and glaciers, the water cycle, steric expansion, and crustal movement is challenging, especially on regional scales. Here, Gravity Recovery And Climate Experiment (GRACE) gravity observations and sea-level anomalies from altimetry are used in a joint inversion, ensuring a consistent decomposition of the global and regional sea-level rise budget. Over the years 2002–2014, we find a global mean steric trend of 1.38 ± 0.16 mm/y, compared with a total trend of 2.74 ± 0.58 mm/y. This is significantly larger than steric trends derived from in situ temperature/salinity profiles and models which range from 0.66 ± 0.2 to 0.94 ± 0.1 mm/y. Mass contributions from ice sheets and glaciers (1.37 ± 0.09 mm/y, accelerating with 0.03 ± 0.02 mm/y2) are offset by a negative hydrological component (−0.29 ± 0.26 mm/y). The combined mass rate (1.08 ± 0.3 mm/y) is smaller than previous GRACE estimates (up to 2 mm/y), but it is consistent with the sum of individual contributions (ice sheets, glaciers, and hydrology) found in literature. The altimetric sea-level budget is closed by coestimating a remaining component of 0.22 ± 0.26 mm/y. Well above average sea-level rise is found regionally near the Philippines (14.7 ± 4.39 mm/y) and Indonesia (8.3 ± 4.7 mm/y) which is dominated by steric components (11.2 ± 3.58 mm/y and 6.4 ± 3.18 mm/y, respectively). In contrast, in the central and Eastern part of the Pacific, negative steric trends (down to −2.8 ± 1.53 mm/y) are detected. Significant regional components are found, up to 5.3 ± 2.6 mm/y in the northwest Atlantic, which are likely due to ocean bottom pressure variations. PMID:26811469

Steric Pressure among Membrane-Bound Polymers Opposes Lipid Phase Separation.

PubMed

Imam, Zachary I; Kenyon, Laura E; Carrillo, Adelita; Espinoza, Isai; Nagib, Fatema; Stachowiak, Jeanne C

2016-04-19

Lipid rafts are thought to be key organizers of membrane-protein complexes in cells. Many proteins that interact with rafts have bulky polymeric components such as intrinsically disordered protein domains and polysaccharide chains. Therefore, understanding the interaction between membrane domains and membrane-bound polymers provides insights into the roles rafts play in cells. Multiple studies have demonstrated that high concentrations of membrane-bound polymeric domains create significant lateral steric pressure at membrane surfaces. Furthermore, our recent work has shown that lateral steric pressure at membrane surfaces opposes the assembly of membrane domains. Building on these findings, here we report that membrane-bound polymers are potent suppressors of membrane phase separation, which can destabilize lipid domains with substantially greater efficiency than globular domains such as membrane-bound proteins. Specifically, we created giant vesicles with a ternary lipid composition, which separated into coexisting liquid ordered and disordered phases. Lipids with saturated tails and poly(ethylene glycol) (PEG) chains conjugated to their head groups were included at increasing molar concentrations. When these lipids were sparse on the membrane surface they partitioned to the liquid ordered phase. However, as they became more concentrated, the fraction of GUVs that were phase-separated decreased dramatically, ultimately yielding a population of homogeneous membrane vesicles. Experiments and physical modeling using compositions of increasing PEG molecular weight and lipid miscibility phase transition temperature demonstrate that longer polymers are the most efficient suppressors of membrane phase separation when the energetic barrier to lipid mixing is low. In contrast, as the miscibility transition temperature increases, longer polymers are more readily driven out of domains by the increased steric pressure. Therefore, the concentration of shorter polymers required to suppress phase separation decreases relative to longer polymers. Collectively, our results demonstrate that crowded, membrane-bound polymers are highly efficient suppressors of phase separation and suggest that the ability of lipid domains to resist steric pressure depends on both their lipid composition and the size and concentration of the membrane-bound polymers they incorporate.

Revisiting the contemporary sea-level budget on global and regional scales.

PubMed

Rietbroek, Roelof; Brunnabend, Sandra-Esther; Kusche, Jürgen; Schröter, Jens; Dahle, Christoph

2016-02-09

Dividing the sea-level budget into contributions from ice sheets and glaciers, the water cycle, steric expansion, and crustal movement is challenging, especially on regional scales. Here, Gravity Recovery And Climate Experiment (GRACE) gravity observations and sea-level anomalies from altimetry are used in a joint inversion, ensuring a consistent decomposition of the global and regional sea-level rise budget. Over the years 2002-2014, we find a global mean steric trend of 1.38 ± 0.16 mm/y, compared with a total trend of 2.74 ± 0.58 mm/y. This is significantly larger than steric trends derived from in situ temperature/salinity profiles and models which range from 0.66 ± 0.2 to 0.94 ± 0.1 mm/y. Mass contributions from ice sheets and glaciers (1.37 ± 0.09 mm/y, accelerating with 0.03 ± 0.02 mm/y(2)) are offset by a negative hydrological component (-0.29 ± 0.26 mm/y). The combined mass rate (1.08 ± 0.3 mm/y) is smaller than previous GRACE estimates (up to 2 mm/y), but it is consistent with the sum of individual contributions (ice sheets, glaciers, and hydrology) found in literature. The altimetric sea-level budget is closed by coestimating a remaining component of 0.22 ± 0.26 mm/y. Well above average sea-level rise is found regionally near the Philippines (14.7 ± 4.39 mm/y) and Indonesia (8.3 ± 4.7 mm/y) which is dominated by steric components (11.2 ± 3.58 mm/y and 6.4 ± 3.18 mm/y, respectively). In contrast, in the central and Eastern part of the Pacific, negative steric trends (down to -2.8 ± 1.53 mm/y) are detected. Significant regional components are found, up to 5.3 ± 2.6 mm/y in the northwest Atlantic, which are likely due to ocean bottom pressure variations.

The French republican model of integration: the theory of cohesion and the practice of exclusion.

PubMed

Oberti, Marco

2008-01-01

What are the explaining factors for the wave of riots in France in November 2005? In providing some answers, this article begins by examining the practical usefulness of the French republican model of integration for social cohesion, highlighting the way its negation of other criteria, such as ethnicity, race, or religion, limit this national conception of citizenship and emphasizing these excluded factors as one of the main causes of frustration and resentment among migrant groups in France.The author compares these riots to the student movements in spring 2006 and shows some similarities as well as important differences between the explaining structural factors of these two youth-based social upheavals. One of the contributing distinctions is the experience of ethnic and racial discrimination as an important source of deep resentment. The author avoids reducing the riots simply to a clash between ethnic groups with specific ethnic interests or a class revolt. Instead, he stresses the relationship between specific social structural factors and spatial effects as the element that created the context for the riots by transforming inequalities into visible and indefensible discrimination. Several factors show that spatial aspects (in the form of segregation) are important alongside the ethnic/racial ones in explaining the riots.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zarkesh, Ryan A.; Foster, Michael E.; Ichimura, Andrew S.

The ability to tune the steric envelope through redox events post-synthetically or in tandem with other chemical processes is a powerful tool that could assist in enabling new catalytic methodologies and understanding potential pitfalls in ligand design. The α-diimine ligand, dmp-BIAN, exhibits the peculiar and previously unreported feature of varying steric profiles depending on oxidation state when paired with a main group element. A study of the factors that give rise to this behaviour as well as its impact on the incorporation of other ligands is performed.

Sterics level the rates of proton transfer to [Ni(XPh){PhP(CH₂CH₂PPh₂)₂}]⁺ (X = O, S or Se).

PubMed

Alwaaly, Ahmed; Henderson, Richard A

2014-09-04

Rates of proton transfers between lutH(+) (lut = 2,6-dimethylpyridine) and [Ni(XPh)(PhP{CH2CH2PPh2}2)](+) (X = O, S or Se) are slow and show little variation (k(O) : k(S) : k(Se) = 1 : 12 : 9). This unusual behaviour is a consequence of sterics affecting the optimal interaction between the reactants prior to proton transfer.

Lutetium functionalities supported by a sterically encumbered β-diketiminate ligand

DOE PAGES

Beattie, Ross J.; Sutton, Andrew D.; Scott, Brian L.; ...

2018-01-06

The sterically encumbered NacNac ligand, [HC(MeCNAr) 2] – (Ar = 2,6- i-Pr 2C 6H 3), was investigated as a platform for supporting Lu-halide complexes, sought for their potential capability of being further converted into hydrocarbyl derivatives via metathetical chemistries with alkali metal alkyls. As a result, these substituted analogs were targeted as potentially viable candidates for alkane elimination chemistries, with an eye towards the formation of an isolable Lu-alkylidene fragment.

Disciplinary Politics and the Institutionalization of the Generic Triad in Classical Rhetoric.

ERIC Educational Resources Information Center

Liu, Yameng

1995-01-01

Discusses the concepts of rhetoric in general and specifically the generic triad in classical rhetoric. Outlines contemporary versions of the function and realm of rhetoric. Discusses the clash between Aristotle and Quintilian regarding the triad and its relationship to contemporary debates. (HB)

Restraints on Dissemination of Research Results.

ERIC Educational Resources Information Center

Taylor, Dalmas A.

1982-01-01

The issue of constraints on the publication of research results is discussed from the perspective of clashing values: free speech versus censorship in protection of national defense. The problems of secrecy as well as of disclosure are examined. Greater conflict between academe and military interests is foreseen. (MSE)

Do Environmental and Energy Goals Clash?

ERIC Educational Resources Information Center

Environmental Science and Technology, 1974

1974-01-01

To meet energy needs, the World's energy base must be broadly diversified. This diversification, including such possibilities as fossil fuels, nuclear, solar, geothermal, tidal and aeolian energy, must proceed without undue environmental damage and be economically feasible. Compromises between energy, economics and the environment will have to be…

Smoking and the First Amendment: A Unit of Study.

ERIC Educational Resources Information Center

Fernekes, William R.

1988-01-01

Provides a model reflective inquiry strategy to educate students about the controversy surrounding the proposed ban on tobacco advertising. Presents a 15-day lesson sequence which explores implications for clashes between individual rights and state power, and includes a list of resources for classroom use. (LS)

Academic Crosswinds: When Professional Ethics and Professional Incentives Clash

ERIC Educational Resources Information Center

O'Neil, Jane

2016-01-01

This article provides a useful and perhaps not uncommon anecdote for researchers thinking about sharing professional expectations, scarce resources, "public good" aspects of academic inquiry, and professional responsibility. It appears as follows: Two sets of researchers, using a respected national longitudinal data set, have been…

The Sanctuary Movement: A Study in Religious Confrontation.

ERIC Educational Resources Information Center

Nelson, Jeffrey; Flannery, Mary Ann

1990-01-01

Examines the clash between the sanctuary movement and United States government regarding the admission to the United States of Central American refugees. Shows through an application of Kenneth Burke's dramatistic approach how different "scenes" operating for the two sides motivate opposing rhetorical agencies. Analyzes those agencies…

Conflict from Teamwork in Project-Based Collaborative Learning

ERIC Educational Resources Information Center

Chan, Lim Ha; Chen, Ching-Huei

2010-01-01

This study investigated the conflict occurring during teamwork among college seniors in project-based collaborative learning in a capstone course. It found that conflict emerged with poor communication, task management, and work allocation; unequal treatments among classmates; egocentricity; a clash of values; and lack of responsibility and…

Receptor-Binding Profiles of H7 Subtype Influenza Viruses in Different Host Species

PubMed Central

Gambaryan, Alexandra S.; Matrosovich, Tatyana Y.; Philipp, Jennifer; Munster, Vincent J.; Fouchier, Ron A. M.; Cattoli, Giovanni; Capua, Ilaria; Krauss, Scott L.; Webster, Robert G.; Banks, Jill; Bovin, Nicolai V.; Klenk, Hans-Dieter

2012-01-01

Influenza viruses of gallinaceous poultry and wild aquatic birds usually have distinguishable receptor-binding properties. Here we used a panel of synthetic sialylglycopolymers and solid-phase receptor-binding assays to characterize receptor-binding profiles of about 70 H7 influenza viruses isolated from aquatic birds, land-based poultry, and horses in Eurasia and America. Unlike typical duck influenza viruses with non-H7 hemagglutinin (HA), all avian H7 influenza viruses, irrespective of the host species, displayed a poultry-virus-like binding specificity, i.e., preferential binding to sulfated oligosaccharides Neu5Acα2-3Galβ1-4(6-O-HSO3)GlcNAc and Neu5Acα2-3Galβ1-4(Fucα1-3)(6-O-HSO3)GlcNAc. This phenotype correlated with the unique amino acid sequence of the amino acid 185 to 189 loop of H7 HA and seemed to be dependent on ionic interactions between the sulfate group of the receptor and Lys193 and on the lack of sterical clashes between the fucose residue and Gln222. Many North American and Eurasian H7 influenza viruses displayed weak but detectable binding to the human-type receptor moiety Neu5Acα2-6Galβ1-4GlcNAc, highlighting the potential of H7 influenza viruses for avian-to-human transmission. Equine H7 influenza viruses differed from other viruses by preferential binding to the N-glycolyl form of sialic acid. Our data suggest that the receptor-binding site of contemporary H7 influenza viruses in aquatic and terrestrial birds was formed after the introduction of their common precursor from ducks to a new host, presumably, gallinaceous poultry. The uniformity of the receptor-binding profile of H7 influenza viruses in various wild and domestic birds indicates that there is no strong receptor-mediated host range restriction in birds on viruses with this HA subtype. This notion agrees with repeated interspecies transmission of H7 influenza viruses from aquatic birds to poultry. PMID:22345462

Towards a Quantitative Understanding of Single-Gene Transcription

NASA Astrophysics Data System (ADS)

O'Maoiléidigh, Dáibhid

2008-03-01

The transcription of the genetic information in DNA into RNA is the first step in protein synthesis. This process is highly regulated and is carried out by RNA polymerase (RNAP), a complex molecular motor. Here we discuss some of the consequences of a Brownian ratchet model of transcription, which incorporates internal structural degrees of freedom of RNAP and kinetic barriers to backtracking of RNAP resulting from steric clashes with co-transcriptionally folded RNA. This approach was previously used (a) to successfully predict sequence dependent positions of pauses during the elongation process [1,2]; (b) to study the behavior of a number of mutants of RNAP, with different elongation behaviors, believed to involve different internal motions of the enzyme [3]; and (c) to gain insight into the interpretation of single-molecule transcription elongation experiments [2]. The same model can be used to characterize the stability of the elongation complex at specific termination sequences, places along DNA where, with high probability, RNAP releases the RNA transcript and disengages from the template. Recent experimental results on termination reinforce a picture of the elongation complex as a flexible structure, not a rigid body [4]. In more general terms, some of the modeling to be presented raises fundamental issues related to ``model comparison'' and ``model selection,'' the problem of identifying and characterizing quantitative models on the basis of limited sets of experimental data [5]. [1] Tadigotla V. R., 'O Maoil'eidigh D., Sengupta A. M., Epshtein V., Ebright R. H., Nudler E., Ruckenstein A. E., Thermodynamic and Kinetic Modeling of Transcriptional Pausing. Proc Natl Acad Sci U S A,03:4439-4444 (2006). [2] D. 'O Maoil'eidigh, Ph.D. Thesis, Rutgers University, 2006 [3] Bar-Nahum, G., Epshtein, V., Ruckenstein, A. E., Rafikov, R., Mustaev, A. and Nudler E., A Ratchet Mechanism of Transcription Elongation and its Control. Cell, 120:183-193 (2005). [4] Epshtein, V., Cardinale, C.J., Ruckenstein, A.E., Borukhov, S., and Nudler, E., An Allosteric Path to Transcription Termination. Mol. Cell,28; 991-1001 (2007). [5] Vasisht R. Tadigotla, Ph.D. Thesis, Rutgers University, 2006

Unitary Responses in Frog Olfactory Epithelium to Sterically Related Molecules at Low Concentrations

PubMed Central

Getchell, Thomas V.

1974-01-01

Responses of receptor cells in the frog's olfactory epithelium were recorded using platinum-black metal-filled microelectrodes. Spontaneous activity varied over a wide range from 0.07 to 1.8 spikes/s. Mean interspike intervals ranged from 13.7 to 0.5 s. Excitatory responses to six sterically related compounds at low concentrations were investigated. Stimuli were delivered in an aqueous medium. Thresholds for impulse initiation varied from greater than 1 mM down to the nanomolar concentration range. Thresholds of different olfactory receptors to the same stimulus could vary by several log units. Thresholds of the same receptor cell to different stimuli could be within the same order of magnitude, or could vary by as much as 5 log units. Based upon quantitative measures of stimulus-evoked excitatory responses it appeared that some receptors did not discriminate among sterically related molecules, whereas other receptors clearly discriminated between stimuli which evoke similar odor sensations. PMID:4211101

Improving halide-containing magnesium-ion electrolyte performance via sterically hindered alkoxide ligands

NASA Astrophysics Data System (ADS)

Nist-Lund, Carl A.; Herb, Jake T.; Arnold, Craig B.

2017-09-01

While homoleptic magnesium dialkoxides (MgR2, R = alkoxide) have shown promise as precursors for magnesium-ion electrolytes, the effect of ligand steric bulk on the performance of electrolytes based on these compounds is not fully understood. Increasing steric hindrance, studied via R groups with additional phenyl moieties, produces electrolytes with sequentially lower deposition overpotentials (less than -90 mV), higher purity Mg deposits (ca. 100% Mg), and lower overall cell impedances. The two largest alkoxide ligands show consistent cycling behavior and low stripping and plating overpotentials over 200 constant-current plating/stripping cycles. A deep-red visual change and the presence of large solubilized magnesium particulates above 450 nm in size is observed in an electrolyte containing magnesium bis(triphenylmethoxide) and aluminum chloride in contact with an abraded magnesium anode. Further morphological and impedance characterization show that this electrolyte system rapidly activates the magnesium metal anode surface to produce low overpotentials and, as such, is a candidate for further investigation.

Small Molecule Activation by Intermolecular Zr(IV)-Phosphine Frustrated Lewis Pairs.

PubMed

Metters, Owen J; Forrest, Sebastian J K; Sparkes, Hazel A; Manners, Ian; Wass, Duncan F

2016-02-17

We report intermolecular transition metal frustrated Lewis pairs (FLPs) based on zirconocene aryloxide and phosphine moieties that exhibit a broad range of small molecule activation chemistry that has previously been the preserve of only intramolecular pairs. Reactions with D2, CO2, THF, and PhCCH are reported. By contrast with previous intramolecular examples, these systems allow facile access to a variety of steric and electronic characteristics at the Lewis acidic and Lewis basic components, with the three-step syntheses of 10 new intermolecular transition metal FLPs being reported. Systematic variation to the phosphine Lewis base is used to unravel steric considerations, with the surprising conclusion that phosphines with relatively small Tolman steric parameters not only give highly reactive FLPs but are often seen to have the highest selectivity for the desired product. DOSY NMR spectroscopic studies on these systems reveal for the first time the nature of the Lewis acid/Lewis base interactions in transition metal FLPs of this type.

Crystallographic Studies of Prion Protein (PrP) Segments Suggest How Structural Changes Encoded by Polymorphism at Residue 129 Modulate Susceptibility to Human Prion Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Apostol, Marcin I.; Sawaya, Michael R.; Cascio, Duilio

2010-09-23

A single nucleotide polymorphism (SNP) in codon 129 of the human prion gene, leading to a change from methionine to valine at residue 129 of prion protein (PrP), has been shown to be a determinant in the susceptibility to prion disease. However, the molecular basis of this effect remains unexplained. In the current study, we determined crystal structures of prion segments having either Met or Val at residue 129. These 6-residue segments of PrP centered on residue 129 are 'steric zippers,' pairs of interacting {beta}-sheets. Both structures of these 'homozygous steric zippers' reveal direct intermolecular interactions between Met or Valmore » in one sheet and the identical residue in the mating sheet. These two structures, plus a structure-based model of the heterozygous Met-Val steric zipper, suggest an explanation for the previously observed effects of this locus on prion disease susceptibility and progression.« less

Using steric hindrance to design new inhibitors of class C beta-lactamases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trehan, Indi; Morandi, F.; Blaszczak, L.C.

{beta}-lactamases confer resistance to {beta}-lactam antibiotics such as penicillins and cephalosporins. However, {beta}-lactams that form an acyl-intermediate with the enzyme but subsequently are hindered from forming a catalytically competent conformation seem to be inhibitors of {beta}-lactamases. This inhibition may be imparted by specific groups on the ubiquitous R1 side chain of {beta}-lactams, such as the 2-amino-4-thiazolyl methoxyimino (ATMO) group common among third-generation cephalosporins. Using steric hindrance of deacylation as a design guide, penicillin and carbacephem substrates were converted into effective {beta}-lactamase inhibitors and antiresistance antibiotics. To investigate the structural bases of inhibition, the crystal structures of the acyl-adducts of themore » penicillin substrate amoxicillin and the new analogous inhibitor ATMO-penicillin were determined. ATMO-penicillin binds in a catalytically incompetent conformation resembling that adopted by third-generation cephalosporins, demonstrating the transferability of such sterically hindered groups in inhibitor design.« less

Impassioned Teaching

ERIC Educational Resources Information Center

Caughie, Pamela L.

2007-01-01

The ongoing debate over academic freedom in venues such as "Academe," the "Chronicle of Higher Education," and the "New York Times" frames the issue in terms of a clash between values and politics on the one hand, and scholarship on the other. The idea that pedagogical responsibility requires toeing a line misrepresents the delicate dynamics of…

The Hybrid Mindset and Operationalizing Innovation: Toward a Theory of Hybrid

DTIC Science & Technology

2014-05-22

relatively large-scale military clashes between Israel and Hezbollah, Operations Accountability (25-31 July 1993) and Grapes of Wrath (11-27 April 1996... Grapes of Wrath (11-27 April 1996) provided Nasrallah and Hezbollah with intelligence on how IDF would attack into southern Lebanon. In addition

Conflict Management and Whole of Government: Useful Tools for U.S. National Security Strategy?

DTIC Science & Technology

2012-04-01

pp 3-16. Durkheim , Emile . Durkheim on Religion. Atlanta, GA: Ameri- can Academy of Religion. 1994. Economist Intelligence Unit, The (EIU). Democracy...15. Huntington, The Clash of Civilizations and the Remaking of World Order, p. 4. 16. Emile Durkheim , Durkheim on Religion, Atlanta, GA: American

Pedagogy Meets Digital Media: A Tangle of Teachers, Strategies, and Tactics

ERIC Educational Resources Information Center

Rust, Julie

2017-01-01

Although increasingly encouraged to incorporate digital media into classrooms to prepare students for engaged participation in a digital world, teachers are often taken by surprise when paradigm clashes arise between traditional school expectations and the affordances of these new spaces. Through data gathered from ethnographic methodologies…

7 Reasons for Accommodating Transgender Students at School

ERIC Educational Resources Information Center

Arenas, Alberto; Gunckel, Kristin L.; Smith, William L.

2016-01-01

Schools have become ground zero for clashes over transgender rights, and critics are denouncing academic institutions--and more recently, the Obama administration--for supporting transgender students in their right to use restrooms and locker rooms that match their gender identity. This article responds to the seven most common claims made by…

Walking in Balance on the Red Road.

ERIC Educational Resources Information Center

Thin Elk, Gene

1993-01-01

Native American who entered treatment for alcohol abuse and found that conventional cures did not address cultural clash of being Indian in Eurocentric society describes alcohol prevention and treatment program rooted in traditional Indian values and ceremonies. Describes "The Red Road," holistic approach which uses culture as therapy and…

Team-Building Success: It's in the Cards

ERIC Educational Resources Information Center

Scarfino, Deborah; Roever, Carol

2009-01-01

Successful team outcomes frequently--if not always--rely upon proven techniques for managing diverse styles and strengths. In this article, the authors describe the Diversity Card Game and the benefits it offers for students and instructors. Building teams using Diversity gives students the knowledge to manage clashes that might otherwise create…

Clash of Harmonics in Stravinsky's "The Rite of Spring"

ERIC Educational Resources Information Center

Ruiz, Michael J.

2018-01-01

This paper describes a fascinating connection between the physics of music and the famous chord in the dissonant rhythmic section of Stravinsky's "The Rite of Spring" (1913). The analysis of Stravinsky's chord will draw from the physics of harmonics, musical intervals, mathematics, and cognitive psychology. This highly interdisciplinary…

Interlanguage Development and Collocational Clash

ERIC Educational Resources Information Center

Shahheidaripour, Gholamabbass

2000-01-01

Background: Persian English learners committed mistakes and errors which were due to insufficient knowledge of different senses of the words and collocational structures they formed. Purpose: The study reported here was conducted for a thesis submitted in partial fulfillment of the requirements for The Master of Arts degree, School of Graduate…

WWW.cell Biology Education: Evolution Web Sites

ERIC Educational Resources Information Center

Liu, Dennis

2005-01-01

The debate over teaching evolution has once again reached a fever pitch in the United States. Earnest nineteenth-century clashes between scientific and religious worldviews have given way to the politically charged arguments of creation science and now intelligent design. The Web site of the National Center for Science Education (NCSE;…

When the Corporate Storm Strikes the Academy: Faculty Response Required

ERIC Educational Resources Information Center

DeBoy, James L.

2015-01-01

When the corporate storm strikes the academy, faculty must be willing and able to repel administrative assaults upon academic freedom, shared governance, and tenure. This paper will describe the on-going clash between administrators who embrace the corporate mindset and faculty who cherish traditions of shared governance and collegial…

The Regional Novel as Textbook

ERIC Educational Resources Information Center

Dubois, Betty Lou

1978-01-01

Describes a novel suitable for university-level English as a foreign language (EFL) courses, Oliver Lafarge's "Laughing Boy." Students are interested in the personal drama of a young Navajo, as well as the broader question of the clash of Navajo and American cultures. Suggestions are given for using this book. (CFM)

Understanding Shakespeare's "Julius Caesar" Online: A Student Casebook to Issues, Sources, and Historical Documents.

ERIC Educational Resources Information Center

Derrick, Thomas

This casebook of materials about William Shakespeare's "Julius Caesar" will enrich students' understanding of the historical context of the play and encourage interpretations of its cultural meaning. Shakespeare's "Julius Caesar" reflects perennial cultural concerns about order and freedom, particularly as they clash in the…

High-Maintenance Parent or Cultural Differences?

ERIC Educational Resources Information Center

Gonzalez-Mena, Janet

2000-01-01

Examines the conflict which can arise when differing cultural practices of families and child care facilities clash. Presents a case study that exemplifies the potential conflict. Provides advice for child care practitioners on how to combine two differing perspectives and how to move from arguments and misunderstandings to common concerns. (SD)

Climbing Mount Everest: Combining Career and Family in Outdoor Education

ERIC Educational Resources Information Center

Allin, Linda

2004-01-01

For women outdoor educators, combining an outdoor career with family relationships appears contradictory. Long and/or irregular hours, residentials, and increasing work commitments are, for example, congruent with traditional notions of a career in the outdoors, yet they clash with social constructions of women's primary identities as partners,…

The U.S. Army in Southeast Asia: Near-Term and Long-Term Roles

DTIC Science & Technology

2013-01-01

clashes sparking naval skirmishes.10 That said, the prospect of the SCS disputes trig- gering a major conflagration with large-scale casualties appears...However, there is a general consensus within ASEAN that these problems constitute concrete security concerns and that defense establish- ments will

Hidden Disruptions: Technology and Technological Literacy as Influences on Professional Writing Student Teams

ERIC Educational Resources Information Center

McGrady, Lisa

2010-01-01

This article reports on a study designed to explore whether and in what ways individual students' technological literacies might impact collaborative teams. For the collaborative team discussed in this article, technological literacy--specifically, limited repertoires for solving technical problems, clashes between document management strategies,…

Hopes and Hazards of Transculturalism

ERIC Educational Resources Information Center

Van Hook, Steven R.

2012-01-01

Educators of international students are frequently challenged by a clashing diversity of cultures in a global classroom. This study examines the sorts of themes and images that might resonate across nationalities and cultures, and could then be used to ease the way for students and educators in international classes. The analysis indicates that…

Leading Schools in the Digital Age: A Clash of Cultures

ERIC Educational Resources Information Center

Williams, Peter

2008-01-01

A cultural gap is widening in English secondary schools: between a twentieth-century ethos of institutional provision and the twenty-first century expectations and digital lifestyles of school students. Perhaps disaffected by traditional teaching methods and the competitive target culture of schools, many students have turned to social networking…

The Taliban Insurgency and an Analysis of ’Shabnamah’ (Night Letters)

DTIC Science & Technology

2007-09-01

regular terminology used by al-Qaeda. It proclaims a clash of civilisations . The declaration accuses the ‘crusaders and their domestic servants’ of...In Violence: Foreign Support Seen Behind Attacks That Mimic Those in Iraq’, Christian Science Monitor, 28 Nov. 2005, p.1. 56. Eric Schmitt

Words-in-Freedom and the Oral Tradition.

ERIC Educational Resources Information Center

Webster, Michael

1989-01-01

Explores how oral and print characteristics mesh or clash in "words-in-freedom," a form of visual poetry invented by Filippo Tommaso Marinetti. Analyzes Marinetti's poster-poem "Apres la Marne, Joffre visita le front en auto," highlighting the different natures of the two media and the coding difficulties occasioned by…

The NATO Special Operations Forces Transformation Initiative: Opportunities and Challenges

DTIC Science & Technology

2009-03-01

reality in the starkest possible terms when British Lieutenant General Sir Michael Jackson refused to comply with the orders of the then-SACEUR...http://www.strategicstudiesinstitute.army.mil/pdffiles/PUB889.pdf (accessed 15 November 2008). 58 General Sir Michael Jackson , “My Clash With NATO

Toward a Field of Interfaith Studies

ERIC Educational Resources Information Center

Patel, Eboo

2013-01-01

Scholars from a range of fields have long taken an interest in how people who orient around religion differently interact with one another. Indeed, this phenomenon has been the subject of important works in political science ("The Clash of Civilizations" by Samuel Huntington), sociology ("American Grace" by Robert Putnam and…

Culturally Relevant Pedagogy: Clashes and Confrontations

ERIC Educational Resources Information Center

Scherff, Lisa, Ed.; Spector, Karen, Ed.

2010-01-01

The authors in this edited volume reflect on their experiences with culturally relevant pedagogy--as students, as teachers, as researchers--and how these experiences were often at odds with their backgrounds and/or expectations. Each of the authors speaks to the complexity and difficulty in attempting to address students' cultures, create learning…

A Bond-Fluctuation Model of Translational Dynamics of Chain-like Particles through Mucosal Scaffolds.

PubMed

Bajd, Franci; Serša, Igor

2018-06-05

Mucus scaffolds represent one of the most common barriers in targeted drug delivery and can remarkably reduce the outcome of pharmacological therapies. An efficient transport of drug particles through a mucus barrier is a precondition for an efficient drug delivery. Understanding the transport mechanism is particularly important for treatment of disorders such as cystic fibrosis. These are characterized by an onset of high-density mucus scaffolds imposing an increased steric filtering. In this study, we employed the bond-fluctuation model to analyze the effect of steric interactions on slowing the translational dynamics of compound chain-like particles traversing through scaffolds of different configurations (regular isotropic and anisotropic versus irregular random). The model, which accounts for both the geometry-imposed steric interaction as well as the intrachain steric interaction between the chain subunits, yields a transient subdiffusive motional pattern persists between the short-time and long-time Gaussian diffusion limits. The motion is analyzed in terms of a mean-squared displacement, diffusion coefficient, and radius of gyration. With higher levels of restriction or larger particles, the subdiffusive motional regime persists longer. The study also demonstrates that an important feature of the motion is also geometry-induced chain accommodation. The presented model is generic and could also be applied to studying the translational dynamics of other particles with more complex architecture such as dendrites or chain-decorated nanoparticles. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Mass-induced [|#8#|]Sea Level Variations in the Red Sea from Satellite Altimetry and GRACE

NASA Astrophysics Data System (ADS)

Feng, W.; Lemoine, J.; Zhong, M.; Hsu, H.

2011-12-01

We have analyzed mass-induced sea level variations (SLVs) in the Red Sea from steric-corrected altimetry and GRACE between January 2003 and December 2010. The steric component of SLVs in the Red Sea calculated from climatological temperature and salinity data is relatively small and anti-phase with the mass-induced SLV. The total SLV in the Red Sea is mainly driven by the mass-induced SLV, which increases in winter when the Red Sea gains the water mass from the Gulf of Aden and vice versa in summer. Spatial and temporal patterns of mass-induced SLVs in the Red Sea from steric-corrected altimetry agree very well with GRACE observations. Both of two independent observations show high annual amplitude in the central Red Sea (>20cm). Total mass-induced SLVs in the Red Sea from two independent observations have similar annual amplitude and phase. One main purpose of our work is to see whether GRGS's ten-day GRACE results can observe intra-seasonal mass change in the Red Sea. The wavelet coherence analysis indicates that GRGS's results show the high correlation with the steric-corrected SLVs on intra-seasonal time scale. The agreement is excellent for all the time-span until 1/3 year period and is patchy between 1/3 and 1/16 year period. Furthermore, water flux estimates from current-meter arrays and moorings show mass gain in winter and mass loss in summer, which is also consistent with altimetry and GRACE.

Steric Shielding of Surface Epitopes and Impaired Immune Recognition Induced by the Ebola Virus Glycoprotein

PubMed Central

Francica, Joseph R.; Varela-Rohena, Angel; Medvec, Andrew; Plesa, Gabriela; Riley, James L.; Bates, Paul

2010-01-01

Many viruses alter expression of proteins on the surface of infected cells including molecules important for immune recognition, such as the major histocompatibility complex (MHC) class I and II molecules. Virus-induced downregulation of surface proteins has been observed to occur by a variety of mechanisms including impaired transcription, blocks to synthesis, and increased turnover. Viral infection or transient expression of the Ebola virus (EBOV) glycoprotein (GP) was previously shown to result in loss of staining of various host cell surface proteins including MHC1 and β1 integrin; however, the mechanism responsible for this effect has not been delineated. In the present study we demonstrate that EBOV GP does not decrease surface levels of β1 integrin or MHC1, but rather impedes recognition by steric occlusion of these proteins on the cell surface. Furthermore, steric occlusion also occurs for epitopes on the EBOV glycoprotein itself. The occluded epitopes in host proteins and EBOV GP can be revealed by removal of the surface subunit of GP or by removal of surface N- and O- linked glycans, resulting in increased surface staining by flow cytometry. Importantly, expression of EBOV GP impairs CD8 T-cell recognition of MHC1 on antigen presenting cells. Glycan-mediated steric shielding of host cell surface proteins by EBOV GP represents a novel mechanism for a virus to affect host cell function, thereby escaping immune detection. PMID:20844579

Stereodynamics in NO(X) + Ar inelastic collisions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brouard, M., E-mail: mark.brouard@chem.ox.ac.uk; Chadwick, H.; Gordon, S. D. S.

2016-06-14

The effect of orientation of the NO(X) bond axis prior to rotationally inelastic collisions with Ar has been investigated experimentally and theoretically. A modification to conventional velocity-map imaging ion optics is described, which allows the orientation of hexapole state-selected NO(X) using a static electric field, followed by velocity map imaging of the resonantly ionized scattered products. Bond orientation resolved differential cross sections are measured experimentally for a series of spin-orbit conserving transitions and compared with quantum mechanical calculations. The agreement between experimental results and those from quantum mechanical calculations is generally good. Parity pairs, which have previously been observed inmore » collisions of unpolarized NO with various rare gases, are not observed due to the coherent superposition of the two j = 1/2, Ω = 1/2 Λ-doublet levels in the orienting field. The normalized difference differential cross sections are found to depend predominantly on the final rotational state, and are not very sensitive to the final Λ-doublet level. The differential steric effect has also been investigated theoretically, by means of quantum mechanical and classical calculations. Classically, the differential steric effect can be understood by considering the steric requirement for different types of trajectories that contribute to different regions of the differential cross section. However, classical effects cannot account quantitatively for the differential steric asymmetry observed in NO(X) + Ar collisions, which reflects quantum interference from scattering at either end of the molecule. This quantum interference effect is dominated by the repulsive region of the potential.« less

Electronic regioselectivity of diarylalkynes in cobalt-mediated Pauson-Khand reaction: an experimental and computational study with para- and meta-substituted diarylalkynes and norbornene.

PubMed

Fager-Jokela, Erika; Muuronen, Mikko; Patzschke, Michael; Helaja, Juho

2012-10-19

Both steric and electronic factors of substituted alkynes are known to guide α/β-cyclopentenone regioselectivity in the cobalt-mediated Pauson-Khand reaction (PKR). In synthetic applications of the PKR, the steric factors can often override or render possible electronic effects. This study examined alkyne-dependent electronic regioselectivity of cyclopentenone formation in PKR with norbornene and sterically equivalent, but electronically unsymmetrical, meta- and para-substituted diarylethynyls to unveil the role of electronic effects alone. In agreement with the literature reports, EDG para-substituted aryls, to some extent, favored the cyclopentenone α-regioisomer, while the EWG-substituted aryls correspondingly preferred the β-regioisomer. The cooperation of EGW and EDG in diaryl-substituted alkynes did not lead to any increased regioselectivities that could be expected by a "push-pull" effect. Both EWG and EDG meta-substituted aryls preferred the β-regioisomer, which was demonstrated by 3,5-dimethoxy- and 3,5-bis(trifluoromethyl)-1-phenylethynyls that yielded 1/1.6 and 1/2.0 α/β-regioselectivities, respectively. Theoretically, inspection of Hammett values of α-alkyne carbons gave qualitatively satisfactory prediction for para-substituted aryls but correlated only weakly with meta-substituted effects. Computational investigations at the DFT level revealed a correlation between NBO charges and the regioselectivity. Overall, the results suggest that the polarity of an alkyne, also designated by the relative polarization of aryl α-carbons, dictates the regioselectivity in the absence of steric effects.

Facile solvolysis of a surprisingly twisted tertiary amide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bloomfield, Aaron J.; Chaudhuri, Subhajyoti; Mercado, Brandon Q.

2016-01-05

In this study, a bicyclo[2.2.2]octane derivative containing both a tertiary amide and a methyl ester was shown crystallographically to adopt a conformation in which the amide is in the cis configuration, which is sterically disfavored, but electronically favored. The steric strain induces a significant torsion (15.9°) of the amide, thereby greatly increasing the solvolytic lability of the amide to the extent that we see competitive amide solvolysis in the presence of the normally more labile methyl ester also present in the molecule.

Negotiation, Not Violence, Is the Rule Today When Students Clash with Administrators.

ERIC Educational Resources Information Center

Collison, Michelle N-K.

1990-01-01

In the 1990s, conflict management is a basic concern of university administrators. Memories of bloody campus confrontations in the 1970s persist, and institutions are reviewing policies on dissent and seeking more appropriate responses to student concerns about racism, tuition increases, gay rights, abortion, and the environment. (MSE)

Pluck & Tenacity: How Five Private Schools in Ohio Have Adapted to Vouchers

ERIC Educational Resources Information Center

Belcher, Ellen

2014-01-01

State-funded voucher programs have stoked political controversy, culture clashes, and pitched court battles. Sometimes referred to as "scholarships," these vouchers enable students of limited means (or without access to a good public school) to attend a private school. Roughly 30,000 children in Ohio take advantage of a publicly funded…

Does Everyone Want Social Justice? Conflicting School Governance Perspectives Regarding Social Justice

ERIC Educational Resources Information Center

Bialik, Gadi; Kalfri, Adv. Yael; Livneh, Idit

2013-01-01

The theoretical grounds underlying this paper are the variety of governance perspectives, which represent different political and economic ideologies (Green, 2005; Manzer, 2003). The coexistence of these often clashing attitudes is one of the reasons for policy ambiguity and policy implementation gaps (Malen, 2006). It can also expose disputing…

Financing Higher Education: Lessons from Economic Theory and Reform in England

ERIC Educational Resources Information Center

Barr, Nicholas

2009-01-01

The finance of higher education faces a clash between technological advance, driving up the demand for skills, and fiscal constraints, given competing imperatives for public spending. Paying for universities is also immensely politically sensitive. This paper sets out core lessons for financing higher education deriving from economic theory,…

Discovering the Common Grading Preferences, Patterns, and Policies of Those Who Assess Writing

ERIC Educational Resources Information Center

Chowske, Rebecca Dunn

2013-01-01

Although considerable attention has been directed at improving the quality of students' writing, the investigation and definition of "good writing" has remained primarily within the realm of the normative and prescriptive. Social scientists and humanists often clash over the definition of valid and reliable writing assessment, as well as…

Clashing Views on Controversial Bioethical Issues. Third Edition. Taking Sides.

ERIC Educational Resources Information Center

Levine, Carol, Ed.

The student who has thoughtfully examined opposing viewpoints on an issue should perceive what other position can be occupied on that issue and should learn to carefully consider antithetical viewpoints. The development of this critical approach is the purpose of this book. An introduction, postscript summary, and two articles or published…

Clashes in the Classroom: The Importance of Norms for Authority.

ERIC Educational Resources Information Center

Metz, Mary Haywood

This paper concentrates on incidents of severe conflict in eighth-grade classrooms observed in studies of four socially diverse junior high schools in two districts. Severe conflict is generated when teachers violate students' conceptions of the character of legitimate classroom authority. In a cosmopolitan community within an urban complex,…

Clashing Views on Controversial Environmental Issues. Third Edition. Taking Sides.

ERIC Educational Resources Information Center

Goldfarb, Theodore D., Ed.

The student who has thoughtfully examined opposing viewpoints on an issue should perceive what other position can be occupied on that issue and should learn to carefully consider antithetical viewpoints. The development of this critical approach is the purpose of this book. An introduction, postscript summary, and pro and con articles or published…

The Legal Environment for Hardwood Lands in California

Treesearch

Sam Doak; Kass Green; Sally K. Fairfax; Sharon G. Johnson

1991-01-01

Intensified use of California's hardwood lands is evolving rapidly. With these changes come clashes over the appropriateness of various land uses and, in some cases, regulatory efforts to control some of these activities. The legal environment facing hardwood landowners is a confusing mix of state, Federal, and local measures. This paper first describes and...

Polarized Discourse in the Egyptian News: Critical Discourse Analysis Perspective

ERIC Educational Resources Information Center

Eissa, Mohammed Mahmoud

2015-01-01

The aim of this study is to investigate ideological structures of polarized discourse coded in the reports of two online news websites: egyptindependent and ikwanweb. The study focuses on online news reports relating to three interrelated events: the issuing of a constitutional declaration by Egyptian president, the aftermath clashes outside…

Science and Security Clash on Bird-Flu Papers

ERIC Educational Resources Information Center

Fischman, Josh

2012-01-01

Censored papers on bird flu, which could help terrorists, have critics wondering if academic scientists can police their own work. The near-publication has brought out general critics of the federal panel, the National Science Advisory Board for Biosecurity, and the voluntary self-policing approach that it embraces instead of regulation. Members…

Nepantlera Pedagogy: An Axiological Posture for Preparing Critically Conscious Teachers in the Borderlands

ERIC Educational Resources Information Center

Reza-López, Elva; Huerta Charles, Luis; Reyes, Loui V.

2014-01-01

Latinos in U.S.-Mexican borderlands encounter language barriers and clashing cultures. If this decade is to become one of transformation, it must grapple with the "uncomfortable" realities of Latino students and other minorities of color. This article delineates the theoretical perspectives of the Nepantlera pedagogy, a pedagogy with an…

A Rationale for Critical Pedagogy in EFL: The Case of Tajikistan

ERIC Educational Resources Information Center

Fredricks, Lori

2007-01-01

As EFL programs become more prevalent throughout the world, the cultural implications of English teaching are more often debated. These cultural considerations are extremely relevant in Islamic cultures, where English education can be viewed as contributing to the influence of Western Christian or secular pedagogy. This potential clash of…

Student-Generated Content: An Approach to Harnessing the Power of Diversity in Higher Education

ERIC Educational Resources Information Center

Snowball, J. D.; McKenna, S.

2017-01-01

Internationally, classes in higher education institutions are becoming larger and more diverse. Support for "non-traditional" students has often taken the form of additional remedial classes offered outside the main curriculum, which has met with limited success. Sociocultural theories of learning argue that the potential clash between…

When Marketisation and Privatisation Clash with Socialist Ideals: Educational Inequality in Urban China

ERIC Educational Resources Information Center

Mok, Ka Ho; Wong, Yu Cheung; Zhang, Xiulan

2009-01-01

In the last two decades, China's education has experienced significant transformations and restructuring on account of privatization and marketization. Unlike the Mao era when the state assumed the major responsibilities in financing and providing education, individuals and families have now to bear increasing financial burdens in paying for…

Culture Clash. Second Edition.

ERIC Educational Resources Information Center

Bache, Ellyn

This monograph provides a first-hand account of the experience of a U.S. family who sponsored a Vietnamese refugee family from 1975-1979. The book, which is comprised of journal entries, proposes to show what it is like to deal with people from an entirely difference culture and to suggest an approach to handling the problems before the…

Rhetoric, Literacy, and Social Change in Post-Mao China

ERIC Educational Resources Information Center

Wexler, Steven

2009-01-01

State, citizen, and corporate readings of a multifarious "Chineseness" fundamentally shape the space where East and West clash in post-Mao China. This dialectic represents a citizen's working-through a crisis of agency and a nation's negotiation of its role within a global economy. Given that China's subaltern literacies operate within…

A Grand Bargain on Quality Assurance?

ERIC Educational Resources Information Center

Taylor, Teresa

2017-01-01

The higher education community faces a wave of challenges. Concerns about affordability and costs have led to questions about the value of higher education to students and society. State and federal funding has been cut or has failed to grow as need has ballooned. Pressures to innovate clash with calls for preserving tradition. Values of academic…

Radicalizing the Ebony Tower: Black Colleges and the Black Freedom Struggle in Mississippi. Reflective History

ERIC Educational Resources Information Center

Williamson, Joy Ann

2008-01-01

This path-breaking examination of Black colleges in Mississippi during Civil Rights and Black Power Movements offers a unique opportunity to understand how institutions are transformed into libratory agents. Williamson examines how campus constituents negotiated and clashed over local, state, and national pressures against the backdrop of the…

Culture Clash or Ties That Bind? What Australian Academics Think of Professional Staff

ERIC Educational Resources Information Center

Gray, Stephen

2015-01-01

This paper uses a framework analysis to explore the opinions a cohort of Australian academic staff hold towards professional staff. Five indicative themes were identified from the extant literature on university professional staff: the professional other; managerialism; an expensive bureaucracy; complementary agendas; and the third space and…

Family Obligations in Micronesian Cultures: Implications for Educators

ERIC Educational Resources Information Center

Ratliffe, Katherine T.

2010-01-01

Micronesian people, a new group of immigrants to the USA, have a strong system of responsibilities to family members that guides their priorities and actions. When family obligations clash with school priorities, conflicts can occur. I interviewed 26 adults to learn about the relationships and responsibilities of family members to each other in…

Teaching Human Rights through Global Education to Teachers in Pakistan

ERIC Educational Resources Information Center

Sadruddin, Munir Moosa

2017-01-01

Pakistan is home to religious and cultural ideologies that greatly support the values of human rights. Nevertheless, the multilayered philosophies of human rights in Pakistan have at times heightened clashes and bred a culture of tension among higher education learners. Ideological filters in national education policies have removed human rights…

"It's Just a Clash of Cultures": Emotional Talk within Medical Students' Narratives of Professionalism Dilemmas

ERIC Educational Resources Information Center

Monrouxe, Lynn V.; Rees, Charlotte E.

2012-01-01

Recent investigations into the UK National Health Service revealed doctors' failures to act with compassion and professionalism towards patients. The British media asked questions about what happens to students during their learning that influences such behaviour as doctors. We listened to 200 medical students' narratives of professionalism…

Black Writers of the Thirties.

ERIC Educational Resources Information Center

Young, James O.

This book is an examination of the ideas of black writers in a variety of political, economic, social, and cultural contexts during the depression years, focusing on published writings of the most prominent writers of the era. Chapters include "Aged Race Men," which examines the clash that occurred in the 1930s between older black leaders and the…

Confrontation and Cooperation: The Complicated Relationship between Homeschoolers and Public Schools

ERIC Educational Resources Information Center

Johnson, Donna M.

2013-01-01

Throughout the modern homeschool movement that emerged in the 1960s and 1970s, homeschooling families have clashed with public institutions. Early homeschoolers joined together to win favorable legislative and judicial outcomes that resulted in the legalization of homeschooling in all 50 states by the early 1990s. Homeschoolers continue to face…

A Clash of Titans: College Football v. Title IX.

ERIC Educational Resources Information Center

Pieronek, Catherine

1994-01-01

Title IX of the Educational Amendments of 1972, Civil Rights Act of 1971, designed to ensure equal educational opportunity for men and women, is reviewed as it pertains to college athletics. Related litigation and National Collegiate Athletic Association efforts to promote compliance are examined, an argument for excluding revenue-producing sports…

Clash of the Titans: Comparing productivity via radiation use efficiency for two grass giants of the biofuel field

USDA-ARS?s Scientific Manuscript database

The comparative productivity of switchgrass (Panicum virgatum L.) and Miscanthus (Miscanthus x giganteus) is of critical importance to the biofuel industry. The radiation use efficiency (RUE), when derived in an environment with non-limiting soil water and soil nutrients, provides one metric of re...

Confronting Asian Concerns in Engaging Learners to Online Education

ERIC Educational Resources Information Center

Subramaniam, Ganakumaran

2008-01-01

Researchers have theorized that cultural emphasis on education plays a major role in explaining Asian students' achievement. While Asian parents often view education as the main vehicle for upward social mobility, the social and cultural make-up of Asian societies and the context within which education is conducted in Asia often clash with the…

Team Teaching Will Work!

ERIC Educational Resources Information Center

Engman, Leila

Research has indicated that teachers are willing to be involved and are capable of being involved in instructional development. According to Kingham and Benham, team teaching has failed in the past due to three causes: a) no planning time, b) personality clashes, and c) inability to integrate the material. To solve these three problems, one can…

Academic Freedom Rights of Students: Some Recent Cases.

ERIC Educational Resources Information Center

Reutter, E. Edmund, Jr.

1996-01-01

Discusses situations that recently received judicial scrutiny regarding clashes between the freedom of the teacher and the freedom of the learner. Each of the following began with a student's objection to an instructional act: (1) freedom to research a religious topic; (2) freedom from racial discomfort; (3) freedom from sexual discomfort; and (4)…

Stifled Voices; Clashing Ideologies: Student Arguments and the American Jeremiad.

ERIC Educational Resources Information Center

Hochenauer, Kurt

The current public debate between the images of the smiling war hero and of the grimacing Vietnam veteran provide opportunities to define two discourse communities that manifest themselves in students' written discourse. These can be seen as akin to the first American jeremiads, which were Puritan treatises written by seventeenth century religious…

Transitioning from High School to College: Surviving a Clash of Educational Cultures. ASHE Annual Meeting Paper.

ERIC Educational Resources Information Center

Lee, Wynetta Y.

This study examined the role of the North Carolina State University Transition Program (UTP) in enhancing transition of disadvantaged students from high school and increasing their persistence to degree. The UTP, which targets academically underprepared African American and Native American students, provides special courses and counseling…

Programmatic Recommendations and Considerations in Assisting School Districts to Serve Vietnamese Children.

ERIC Educational Resources Information Center

Maldonado, Stephen

The seminar reported here focused on identifying the needs and problems of Vietnamese children and adults. These included bilingual education, culture clash, second language programs, and educational differences between Vietnam and the U.S. It was observed that teachers must be prepared to respond to their Vietnamese students according to their…

Visions of History: The Aztecs and the Spanish.

ERIC Educational Resources Information Center

Nunez, Lucia

This unit is guided by the question "How is history constructed?" In this unit, middle to secondary school students explore a variety of accounts of the clash of cultures that occurred between the Spanish and the Aztecs. Students examine a variety of primary sources and analyze the various perspectives presented. The six activities…

The Amish and the State.

ERIC Educational Resources Information Center

Kraybill, Donald B., Ed.

The opportunity for religious freedom brought the Amish from Europe to North America as early as 1737. And for many generations, conflicts between the Amish and the U.S. government were limited to Amish objections to military service. However, as the government's regulatory power grew in the 20th century, clashes between the Amish and the state…

Clashes within One Teacher's Racial Logic: Space of Possibles?

ERIC Educational Resources Information Center

Shim, Jenna Min

2013-01-01

This study is to empirically investigate both residual and emergent factors that undergird one teacher's understanding of race, racism, and racialization as he responds to two fictional stories and one film. Informed by an assemblage of Bourdieu's concept of habitus and his sociological theory of practice, Gee's concept of primary Discourses, and…

Functional Literacy Empowerment for Nomadic Herdsmen in Osun State, Nigeria

ERIC Educational Resources Information Center

Olateju, Mojisola Ajibike

2010-01-01

The need for adequate functional English literacy and numeracy instruction for the herdsmen in Osun State in Nigeria arose as a result of the persistent clashes between the herdsmen and their neighbours. In all, 48 participants (22 adults and 26 children and youths) took part in the International Reading Association assisted functional literacy…

The Practicum Course Model: Embracing the Museum-University Culture Clash

ERIC Educational Resources Information Center

Kingsley, Jennifer P.

2016-01-01

Museums and universities have natural connections. Yet with few exceptions, collaborations between them segregate each partner to its traditional sphere of activity. This article presents a practicum course model that blurs and overlaps the distinctive roles of the museum and university in productive and mutually beneficial ways. In particular,…

Religion and Education: A Human Rights Dilemma Illustrated by the Recent "Headscarf Cases"

ERIC Educational Resources Information Center

Smith, Rhona K. M.

2007-01-01

Education and religion are indelibly linked: cultural precepts underpin education policies within the formal State education system, while education has a clear role to play in promoting tolerance. Clashes between religious beliefs and secular education pose problems for states as the current array of jurisprudence, particularly on Islamic dress…

Getting Personal: Responding to Student Self-Disclosure

ERIC Educational Resources Information Center

Lucas, Janet

2007-01-01

While some scholars in English and other disciplines disparage personal narrative writing by students, it can serve as a conversational bridge between students' home cultures and academic culture and as a contact zone where those cultures can clash yet be explored; however, instructors and others who work with student writing must be prepared…

How Does Collegiality Survive Managerially Led Universities? Evidence from a European Survey

ERIC Educational Resources Information Center

Marini, Giulio; Reale, Emanuela

2016-01-01

Today's universities are, accordingly to Clark's entrepreneurial model, sustained by managerialism, whereas collegialism may remain in contrast or work in a different way. More recent literature suggests the clash such as the potential for coexistence between managerialism and collegialism. The study analyses data from a survey of 26 universities…

Reinvention: The Promise and Challenge of Transforming a Community College System

ERIC Educational Resources Information Center

Hyman, Cheryl L.

2018-01-01

"Reinvention" chronicles an unprecedentedly comprehensive approach to community college reform and the leadership challenges encountered along the way. The book addresses cultural clashes over the role and purpose of community colleges and argues for an emphasis on success and access. As chancellor of the City Colleges of Chicago, Cheryl…

Culture Clash in the Multicultural Classroom: A Case Study from A Newcomer School

ERIC Educational Resources Information Center

Hansen-Thomas, Holly; Chennapragada, SriPadmini

2018-01-01

This ethnographic case study of a multicultural/multilingual classroom in a newcomer school describes an incident that occurred among new immigrant English Language Learners from widely diverse backgrounds in a secondary classroom in Texas. Increased numbers of immigrant students in U.S. schools have resulted in classrooms with tremendous…

Cultural Diversity in Classrooms: What Teachers Need To Know.

ERIC Educational Resources Information Center

Sandhu, Daya Singh

This paper emphasizes the significance of cultural diversity in American schools and its implications for the teaching and learning processes. Also highlighted is the importance of the realization that diversity is what makes the United States unique. The paper discusses the cultural dynamics of clashes and conflicts as well as of cooperation and…

Dialogue through Standpoint: Understanding Women's and Men's Standpoints of Sexual Harassment.

ERIC Educational Resources Information Center

Dougherty, Debbie S.

1999-01-01

Contributes to scholarship on sexual harassment. Finds that men's "power over" standpoint and the related fear of marginalization clash with women's "power with" standpoint and the related fear of physical harm. Argues that managers and researchers need to understand both standpoints to better understand the dynamics of sexual harassment and how…

The News Media and the Government: Clash of Concentrated Power.

ERIC Educational Resources Information Center

Freedom House, Inc., New York, NY.

This document brings together news media and constitutional law specialists with past and present government officials to define the areas of conflict and the operative constitutional rules and to devise ways to maximize the flow of information to the public without destructive confrontations between the media and government. Contents include:…

Collision of Epistemological Frameworks: Religion and Social Science's Unshared Understanding of Ethics

ERIC Educational Resources Information Center

Firmin, Michael W.

2009-01-01

Religious scholars and social science experts frequently differ and sometimes clash when writing and discussing issues of ethics. Sometimes unshared understandings on fundamental world-view issues is the etiology for these differences. Differences in defining truth, whether philosophically or empirically, often is at the root etiology in these…

Synthesis, characterization and electroluminescence of two highly-twisted non-doped blue light-emitting materials

NASA Astrophysics Data System (ADS)

Gong, Xiaojie; Pan, Yipeng; Xie, Xiang; Tong, Tong; Chen, Runfeng; Gao, Deqing

2018-04-01

Two pyrene derivatives, substituted with 2-methylnaphthalene units on 1,3-position and 1,6-position of pyrene backbones, were designed and synthesized. DFT calculation confirmed that the two molecules were highly twisted and the dihedral angles between pyrene backbone and naphthalene unit were over 80°, being attributed to the steric hindrance of ortho-methyl group and the substitution position of pyrene itself. As a result, the intermolecular aggregation was greatly inhibited in the solid state, being beneficial for suppressing the fluorescence quenching. By analyzing the optical and thermal properties, it was found that the π-π conjugation extension could be adjusted and a balance for high fluorescent efficiency and avoiding quenching at the same time could be reached, which may guide the molecular design in the future. The electroluminescence properties of the non-doped devices were enhanced with the double hole-transporting layers by optimizing the energy level matching. The stable blue EL emission, with the Commission Internationaled'Eclairage (CIEx,y) color coordinates of (0.15, 0.13) and (0.15, 0.11) at 7, 8, 9 and 10 V respectively, was obtained.

Abasic pivot substitution harnesses target specificity of RNA interference

PubMed Central

Lee, Hye-Sook; Seok, Heeyoung; Lee, Dong Ha; Ham, Juyoung; Lee, Wooje; Youm, Emilia Moonkyung; Yoo, Jin Seon; Lee, Yong-Seung; Jang, Eun-Sook; Chi, Sung Wook

2015-01-01

Gene silencing via RNA interference inadvertently represses hundreds of off-target transcripts. Because small interfering RNAs (siRNAs) can function as microRNAs, avoiding miRNA-like off-target repression is a major challenge. Functional miRNA–target interactions are known to pre-require transitional nucleation, base pairs from position 2 to the pivot (position 6). Here, by substituting nucleotide in pivot with abasic spacers, which prevent base pairing and alleviate steric hindrance, we eliminate miRNA-like off-target repression while preserving on-target activity at ∼80–100%. Specifically, miR-124 containing dSpacer pivot substitution (6pi) loses seed-mediated transcriptome-wide target interactions, repression activity and biological function, whereas other conventional modifications are ineffective. Application of 6pi allows PCSK9 siRNA to efficiently lower plasma cholesterol concentration in vivo, and abolish potentially deleterious off-target phenotypes. The smallest spacer, C3, also shows the same improvement in target specificity. Abasic pivot substitution serves as a general means to harness the specificity of siRNA experiments and therapeutic applications. PMID:26679372

Concentrated Solutions of Single-Chain Nanoparticles: A Simple Model for Intrinsically Disordered Proteins under Crowding Conditions.

PubMed

Moreno, Angel J; Lo Verso, Federica; Arbe, Arantxa; Pomposo, José A; Colmenero, Juan

2016-03-03

By means of large-scale computer simulations and small-angle neutron scattering (SANS), we investigate solutions of single-chain nanoparticles (SCNPs), covering the whole concentration range from infinite dilution to melt density. The analysis of the conformational properties of the SCNPs reveals that these synthetic nano-objects share basic ingredients with intrinsically disordered proteins (IDPs), as topological polydispersity, generally sparse conformations, and locally compact domains. We investigate the role of the architecture of the SCNPs in their collapse behavior under macromolecular crowding. Unlike in the case of linear macromolecules, which experience the usual transition from self-avoiding to Gaussian random-walk conformations, crowding leads to collapsed conformations of SCNPs resembling those of crumpled globules. This behavior is already found at volume fractions (about 30%) that are characteristic of crowding in cellular environments. The simulation results are confirmed by the SANS experiments. Our results for SCNPs--a model system free of specific interactions--propose a general scenario for the effect of steric crowding on IDPs: collapse from sparse conformations at high dilution to crumpled globular conformations in cell environments.

Design attributes of long-circulating polymeric drug delivery vehicles.

PubMed

Beck-Broichsitter, Moritz; Nicolas, Julien; Couvreur, Patrick

2015-11-01

Following systemic administration polymeric drug delivery vehicles allow for a controlled and targeted release of the encapsulated medication at the desired site of action. For an elevated and organ specific accumulation of their cargo, nanocarriers need to avoid opsonization, activation of the complement system and uptake by macrophages of the mononuclear phagocyte system. In this respect, camouflaged vehicles revealed a delayed elimination from systemic circulation and an improved target organ deposition. For instance, a steric shielding of the carrier surface by poly(ethylene glycol) substantially decreased interactions with the biological environment. However, recent studies disclosed possible deficits of this approach, where most notably, poly(ethylene glycol)-modified drug delivery vehicles caused significant immune responses. At present, identification of novel potential carrier coating strategies facilitating negligible immune reactions is an emerging field of interest in drug delivery research. Moreover, physical carrier properties including geometry and elasticity seem to be very promising design attributes to surpass numerous biological barriers, in order to improve the efficacy of the delivered medication. Copyright © 2015 Elsevier B.V. All rights reserved.

Enantioselective Rhodium-Catalyzed [2+2+2] Cycloadditions of Terminal Alkynes and Alkenyl Isocyanates: Mechanistic Insights Lead to a Unified Model that Rationalizes Product Selectivity

PubMed Central

Dalton, Derek M.; Oberg, Kevin M.; Yu, Robert T.; Lee, Ernest E.; Perreault, Stéphane; Oinen, Mark Emil; Pease, Melissa L.; Malik, Guillaume; Rovis, Tomislav

2009-01-01

This manuscript describes the development and scope of the asymmetric rhodium-catalyzed [2+2+2] cycloaddition of terminal alkynes and alkenyl isocyanates leading to the formation of indolizidine and quinolizidine scaffolds. The use of phosphoramidite ligands proved crucial for avoiding competitive terminal alkyne dimerization. Both aliphatic and aromatic terminal alkynes participate well, with product selectivity a function of both the steric and electronic character of the alkyne. Manipulation of the phosphoramidite ligand leads to tuning of enantio- and product selectivity, with a complete turnover in product selectivity seen with aliphatic alkynes when moving from Taddol-based to biphenol-based phosphoramidites. Terminal and 1,1-disubstituted olefins are tolerated with nearly equal efficacy. Examination of a series of competition experiments in combination with analysis of reaction outcome shed considerable light on the operative catalytic cycle. Through a detailed study of a series of X-ray structures of rhodium(cod)chloride/phosphoramidite complexes, we have formulated a mechanistic hypothesis that rationalizes the observed product selectivity. PMID:19817441

A study on an unusual SN2 mechanism in the methylation of benzyne through nickel-complexation.

PubMed

Hatakeyama, Makoto; Sakamoto, Yuki; Ogata, Koji; Sumida, Yuto; Sumida, Tomoe; Hosoya, Takamitsu; Nakamura, Shinichiro

2017-10-11

In this study, three reaction mechanisms of a benzyne-nickel (Ni) complex ([Ni(C 6 H 4 )(dcpe)]) with iodomethane during the methylation process were investigated, namely (a) S N 2 reaction of the benzyne-Ni complex with iodomethane, (b) concerted σ-bond metathesis during the bond breaking/forming processes, and (c) oxidative addition of iodomethane to the Ni-center and the subsequent reductive elimination process. DFT calculations revealed that the reaction barrier of the S N 2 reaction is slightly lower than those of the other mechanisms. The results of orbital analyses suggest that [Ni(C 6 H 4 )(dcpe)] forms a metallacycle structure between benzyne and the Ni II (3d 8 ) center instead of the η 2 -structure with the Ni 0 (3d 10 ) center. The metallacycle structures became inappropriate as the intermediates of oxidative addition in the formation of the Ni II -Me bond, avoiding further oxidation to the high-valent Ni IV . The high free energy along σ-bond metathesis was generated from the steric hindrance, thus invoking methylation and Ni-I bond formation concertedly.

Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain

PubMed Central

Mastorakos, Panagiotis; Song, Eric; Zhang, Clark; Berry, Sneha; Park, Hee Won; Kim, Young Eun; Park, Jong Sung; Lee, Seulki; Suk, Jung Soo; Hanes, Justin

2016-01-01

Successful gene therapy of neurological disorders is predicated on achieving widespread and uniform transgene expression throughout the affected disease area in the brain. However, conventional gene vectors preferentially travel through low-resistance perivascular spaces and/or are confined to the administration site even with the aid of a pressure-driven flow provided by convection-enhanced delivery. Biodegradable DNA nanoparticles offer a safe gene delivery platform devoid of adverse effects associated with virus-based or synthetic non-biodegradable systems. Using a state-of-the-art biodegradable polymer, poly(β-amino ester), we engineered colloidally stable sub-100 nm DNA nanoparticles coated with a non-adhesive polyethylene glycol corona that are able to avoid the adhesive and steric hindrances imposed by the extracellular matrix. Following convection enhanced delivery, these brain-penetrating nanoparticles were able to homogeneously distribute throughout the rodent striatum and mediate widespread and high-level transgene expression. These nanoparticles provide a biodegradable DNA nanoparticle platform enabling uniform transgene expression patterns in vivo and hold promise for the treatment of neurological diseases. PMID:26680637

Measurements and Quasi-Quantum Modeling of the Steric Asymmetry and Parity Propensities in State-to-State Rotationally Inelastic Scattering of NO ( 2Π 1/2) with D 2

DOE PAGES

Taatjes, Craig A.; Gijsbertsen, Arjan; de Lange, Marc J. L.; ...

2007-06-02

In this paper, relative integrated cross sections are measured for spin-orbit-conserving, rotationally inelastic scattering of NO ( 2Π 1/2), hexapole-selected in the upper Λ-doublet level of the ground rotational state (j = 0.5), in collisions with D 2 at a nominal energy of 551 cm -1. The final state of the NO molecule is detected by laser-induced fluorescence (LIF). The state-selected NO molecule is oriented with either the N end or the O end toward the incoming D 2 molecule by application of a static electric field E in the scattering region. This field is directed parallel or antiparallel tomore » the relative velocity vector v. Comparison of signals taken for the different applied field directions gives the experimental steric asymmetry SA, defined by SA = (σ v↑↓E - σ v↑↑E)/(σ v↑↓E + σ v↑↑E), which is equal to within a factor of -1 to the molecular steric effect, S i→f ≡ (σ D2→NO - σ D2→ON)/(σ D2→NO + σ D2→ON). The dependence of the integral inelastic cross section on the incoming Λ-doublet component is also measured as a function of the final rotational (j final) and Λ-doublet (ε final) state. The measured steric asymmetries are similar to those previously observed for NO-He scattering. Spin-orbit manifold-conserving collisions exhibit a larger propensity for parity conservation than their NO-He counterparts. The results are interpreted in the context of the recently developed quasi-quantum treatment (QQT) of rotationally inelastic scattering. The QQT predictions can be inverted to obtain a fitted hard-shell potential that reproduces the experimental steric asymmetry; this fitted potential gives an empirical estimate of the anisotropy of the repulsive interaction between NO and D 2. Finally, QQT computation of the differential cross section using this simple model potential shows reasonable agreement with the measured differential cross sections.« less

Sea level budget in the Arctic during the satellite altimetry era

NASA Astrophysics Data System (ADS)

Carret, Alice; Cazenave, Anny; Meyssignac, Benoît; Prandi, Pierre; Ablain, Michael; Andersen, Ole; Blazquez, Alejandro

2016-04-01

Studying sea level variations in the Arctic region is challenging because of data scarcity. Here we present results of the sea level budget in the Arctic (up to 82°N) during the altimetry era. We first investigate closure of the sea level budget since 2002 using altimetry data from Envisat and Cryosat for estimating sea level, temperature and salinity data from the ORAP5 reanalysis and GRACE space gravimetry to estimate the steric and mass components. Two altimetry sea level data sets are considered (from DTU and CLS), based on Envisat waveforms retracking. Regional sea level trends seen in the altimetric map, in particular over the Beaufort Gyre and along the eastern coast of Greenland are of steric origin. However, in terms of regional average, the steric component contributes very little to the observed sea level trend, suggesting a dominant mass contribution in the Arctic region. This is confirmed by GRACE-based ocean mass time series that agree very well with the altimetry-based sea level time series. Direct estimate of the mass component is not possible prior to GRACE. Thus we estimated the mass contribution over the whole altimetry era from the difference between altimetry-based sea level and the ORAP5 steric component. Finally we compared altimetry-based coastal sea level with tide gauge records available along Norwegian, Greenland and Siberian coastlines and investigated whether the Arctic Oscillation that was the main driver of coastal sea level in the Arctic during the past decades still plays a dominant role or if other factors (e.g., of anthropogenic origin) become detectable.

Establishment of Constraints on Amyloid Formation Imposed by Steric Exclusion of Globular Domains.

PubMed

Azizyan, Rafayel A; Garro, Adriana; Radkova, Zinaida; Anikeenko, Alexey; Bakulina, Anastasia; Dumas, Christian; Kajava, Andrey V

2018-06-01

In many disease-related and functional amyloids, the amyloid-forming regions of proteins are flanked by globular domains. When located in close vicinity of the amyloid regions along the chain, the globular domains can prevent the formation of amyloids because of the steric repulsion. Experimental tests of this effect are few in number and non-systematic, and their interpretation is hampered by polymorphism of amyloid structures. In this situation, modeling approaches that use such a clear-cut criterion as the steric tension can give us highly trustworthy results. In this work, we evaluated this steric effect by using molecular modeling and dynamics. As an example, we tested hybrid proteins containing an amyloid-forming fragment of Aβ peptide (17-42) linked to one or two globular domains of GFP. Searching for the shortest possible linker, we constructed models with pseudo-helical arrangements of the densely packed GFPs around the Aβ amyloid core. The molecular modeling showed that linkers of 7 and more residues allow fibrillogenesis of the Aβ-peptide flanked by GFP on one side and 18 and more residues when Aβ-peptide is flanked by GFPs on both sides. Furthermore, we were able to establish a more general relationship between the size of the globular domains and the length of the linkers by using analytical expressions and rigid body simulations. Our results will find use in planning and interpretation of experiments, improvement of the prediction of amyloidogenic regions in proteins, and design of new functional amyloids carrying globular domains. Copyright © 2018 Elsevier Ltd. All rights reserved.

3D-QSAR CoMFA of a series of DABO derivatives as HIV-1 reverse transcriptase non-nucleoside inhibitors.

PubMed

de Brito, Monique Araújo; Rodrigues, Carlos Rangel; Cirino, José Jair Vianna; de Alencastro, Ricardo Bicca; Castro, Helena Carla; Albuquerque, Magaly Girão

2008-08-01

A series of 74 dihydroalkoxybenzyloxopyrimidines (DABOs), a class of highly potent non-nucleoside reverse transcriptase inhibitors (NNRTIs), was retrieved from the literature and studied by comparative molecular field analysis (CoMFA) in order to derive three-dimensional quantitative structure-activity relationship (3D-QSAR) models. The CoMFA study has been performed with a training set of 59 compounds, testing three alignments and four charge schemes (DFT, HF, AM1, and PM3) and using defaults probe atom (Csp (3), +1 charge), cutoffs (30 kcal.mol (-1) for both steric and electrostatic fields), and grid distance (2.0 A). The best model ( N = 59), derived from Alignment 1 and PM3 charges, shows q (2) = 0.691, SE cv = 0.475, optimum number of components = 6, r (2) = 0.930, SEE = 0.226, and F-value = 115.544. The steric and electrostatic contributions for the best model were 43.2% and 56.8%, respectively. The external predictive ability (r (2) pred = 0.918) of the resultant best model was evaluated using a test set of 15 compounds. In order to design more potent DABO analogues as anti-HIV/AIDS agents, attention should be taken in order to select a substituent for the 4-oxopyrimidine ring, since, as revealed by the best CoMFA model, there are a steric restriction at the C2-position, a electron-rich group restriction at the C6-position ( para-substituent of the 6-benzyl group), and a steric allowed region at the C5-position.

Steric and electrostatic surface forces on sulfonated PEG graft surfaces with selective albumin adsorption.

PubMed

Bremmell, Kristen E; Britcher, Leanne; Griesser, Hans J

2013-06-01

Addition of ionized terminal groups to PEG graft layers may cause additional interfacial forces to modulate the net interfacial interactions between PEG graft layers and proteins. In this study we investigated the effect of terminal sulfonate groups, characterizing PEG-aldehyde (PEG-CHO) and sulfonated PEG (PEG-SO3) graft layers by XPS and colloid probe AFM interaction force measurements as a function of ionic strength, in order to determine surface forces relevant to protein resistance and models of bio-interfacial interaction of such graft coatings. On the PEG-CHO surface the measured interaction force does not alter with ionic strength, typical of a repulsive steric barrier coating. An analogous repulsive interaction force of steric origin was also observed on the PEG-SO3 graft coating; however, the net interaction force changed with ionic strength. Interaction forces were modelled by steric and electrical double layer interaction theories, with fitting to a scaling theory model enabling determination of the spacing and stretching of the grafted chains. Albumin, fibrinogen, and lysozyme did not adsorb on the PEG-CHO coating, whereas the PEG graft with terminal sulfonate groups showed substantial adsorption of albumin but not fibrinogen or lysozyme from 0.15 M salt solutions. Under lower ionic strength conditions albumin adsorption was again minimized as a result of the increased electrical double-layer interaction observed with the PEG-SO3 modified surface. This unique and unexpected adsorption behaviour of albumin provides an alternative explanation to the "negative cilia" model used by others to rationalize observed thromboresistance on PEG-sulfonate coatings. Copyright © 2013 Elsevier B.V. All rights reserved.

Deterministic folding: The role of entropic forces and steric specificities

NASA Astrophysics Data System (ADS)

da Silva, Roosevelt A.; da Silva, M. A. A.; Caliri, A.

2001-03-01

The inverse folding problem of proteinlike macromolecules is studied by using a lattice Monte Carlo (MC) model in which steric specificities (nearest-neighbors constraints) are included and the hydrophobic effect is treated explicitly by considering interactions between the chain and solvent molecules. Chemical attributes and steric peculiarities of the residues are encoded in a 10-letter alphabet and a correspondent "syntax" is provided in order to write suitable sequences for the specified target structures; twenty-four target configurations, chosen in order to cover all possible values of the average contact order χ (0.2381⩽χ⩽0.4947 for this system), were encoded and analyzed. The results, obtained by MC simulations, are strongly influenced by geometrical properties of the native configuration, namely χ and the relative number φ of crankshafts-type structures: For χ<0.35 the folding is deterministic, that is, the syntax is able to encode successful sequences: The system presents larger encodability, minimum sequence-target degeneracies and smaller characteristic folding time τf. For χ⩾0.35 the above results are not reproduced any more: The folding success is severely reduced, showing strong correlation with φ. Additionally, the existence of distinct characteristic folding times suggests that different mechanisms are acting at the same time in the folding process. The results (all obtained from the same single model, under the same "physiological conditions") resemble some general features of the folding problem, supporting the premise that the steric specificities, in association with the entropic forces (hydrophobic effect), are basic ingredients in the protein folding process.

Synthesis and physicochemical studies of amyloidogenic hexapeptides derived from human cystatin C.

PubMed

Iłowska, Emilia; Sawicka, Justyna; Szymańska, Aneta

2018-06-01

Human cystatin C (hCC) is a low molecular mass protein that belongs to the cystatin superfamily. It is an inhibitor of extracellular cysteine proteinases, present in all human body fluids. At physiological conditions, hCC is a monomer, but it has a tendency to dimerization. Naturally occurring hCC mutant, with leucine in position 68 substituted by glutamine (L68Q), is directly involved in the formation of amyloid deposits, independently of other proteins. This process is the primary cause of hereditary cerebral amyloid angiopathy, observed mainly in the Icelandic population. Oligomerization and fibrillization processes of hCC are not explained equally well, but it is proposed that domain swapping is involved in both of them. Research carried out on the fibrillization process led to new hypothesis about the existence of a steric zipper motif in amyloidogenic proteins. In the hCC sequence, there are 2 fragments which may play the role of a steric zipper: the loop L1 region and the C-terminal fragment. In this work, we focused on the first of these. Nine hexapeptides covering studied hCC fragment were synthesized, and their fibrillogenic potential was assessed using an array of biophysical methods. The obtained results showed that the studied hCC fragment has strong profibrillogenic propensities because it contains 2 fragments fulfilling the requirements for an effective steric zipper located next to each other, forming 1 super-steric zipper motif. This hCC fragment might therefore be responsible for the enhanced amyloidogenic properties of dimeric or partially unfolded hCC. Copyright © 2018 European Peptide Society and John Wiley & Sons, Ltd.

Revealing climate modes in steric sea levels: lessons learned from satellite geodesy, objective analyses and ocean reanalyses

NASA Astrophysics Data System (ADS)

Pfeffer, J.; Tregoning, P.; Purcell, A. P.

2017-12-01

Due to increased greenhouse gases emissions, the oceans are accumulating heat. In response to the ocean circulation and atmospheric forcing, the heat is irregularly redistributed within the oceans, causing sea level to rise at variable rates in space and time. These rates of steric expansion are extremely difficult to assess because of the sparsity of in-situ hydrographic observations available within the course of the 20th century. We compare here three methods to reconstruct the steric sea levels over the past 13, 25 and 58 years based on satellite geodesy, objective analyses and ocean reanalyses. The interannual to decadal variability of each dataset is explored with a model merging six climate indices representative of the natural variability of the ocean and climate system. Consistent regional patterns are identified for the Pacific Decadal Oscillation (PDO) and El Niño Southern Oscillation (ENSO) in all datasets at all timescales. Despite the short time coverage (13 years), the combination of satellite geodetic data (altimetry and GRACE) also reveals significant steric responses to the North Pacific Gyre Oscillation (NPGO), Indian Dipole (IOD) and Indian ocean basinwide (IOBM) mode. The richer information content in the ocean reanalyses allows us to recover the regional fingerprints of the PDO, ENSO, NPGO, IOD and IOBM, but also of the Atlantic Multidecadal Oscillation (AMO) acting over longer time scales (40 to 60 years). Therefore, ocean reanalyses, coupled with climate mode analyses, constitute innovative and promising tools to investigate the mechanisms triggering the variability of sea level rise over the past decades.

Star Formation Activity in CLASH Brightest Cluster Galaxies

NASA Astrophysics Data System (ADS)

Fogarty, Kevin; Postman, Marc; Connor, Thomas; Donahue, Megan; Moustakas, John

2015-11-01

The CLASH X-ray selected sample of 20 galaxy clusters contains 10 brightest cluster galaxies (BCGs) that exhibit significant (>5σ) extinction-corrected star formation rates (SFRs). Star formation activity is inferred from photometric estimates of UV and Hα+[N ii] emission in knots and filaments detected in CLASH Hubble Space Telescope ACS and WFC3 observations. UV-derived SFRs in these BCGs span two orders of magnitude, including two with a SFR ≳ 100 M⊙ yr-1. These measurements are supplemented with [O ii], [O iii], and Hβ fluxes measured from spectra obtained with the SOAR telescope. We confirm that photoionization from ongoing star formation powers the line emission nebulae in these BCGs, although in many BCGs there is also evidence of a LINER-like contribution to the line emission. Coupling these data with Chandra X-ray measurements, we infer that the star formation occurs exclusively in low-entropy cluster cores and exhibits a correlation with gas properties related to cooling. We also perform an in-depth study of the starburst history of the BCG in the cluster RXJ1532.9+3021, and create 2D maps of stellar properties on scales down to ˜350 pc. These maps reveal evidence for an ongoing burst occurring in elongated filaments, generally on ˜0.5-1.0 Gyr timescales, although some filaments are consistent with much younger (≲100 Myr) burst timescales and may be correlated with recent activity from the active galactic nucleus. The relationship between BCG SFRs and the surrounding intracluster medium gas properties provide new support for the process of feedback-regulated cooling in galaxy clusters and is consistent with recent theoretical predictions. Based on observations obtained at the Southern Astrophysical Research (SOAR) telescope, which is a joint project of the Ministério da Ciência, Tecnologia, e Inovação (MCTI) da República Federativa do Brasil, the U.S. National Optical Astronomy Observatory (NOAO), the University of North Carolina at Chapel Hill (UNC), and Michigan State University (MSU).

Three gravitationally lensed supernovae behind clash galaxy clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patel, Brandon; McCully, Curtis; Jha, Saurabh W.

2014-05-01

We report observations of three gravitationally lensed supernovae (SNe) in the Cluster Lensing And Supernova survey with Hubble (CLASH) Multi-Cycle Treasury program. These objects, SN CLO12Car (z = 1.28), SN CLN12Did (z = 0.85), and SN CLA11Tib (z = 1.14), are located behind three different clusters, MACSJ1720.2+3536 (z = 0.391), RXJ1532.9+3021 (z = 0.345), and A383 (z = 0.187), respectively. Each SN was detected in Hubble Space Telescope optical and infrared images. Based on photometric classification, we find that SNe CLO12Car and CLN12Did are likely to be Type Ia supernovae (SNe Ia), while the classification of SN CLA11Tib is inconclusive.more » Using multi-color light-curve fits to determine a standardized SN Ia luminosity distance, we infer that SN CLO12Car was ∼1.0 ± 0.2 mag brighter than field SNe Ia at a similar redshift and ascribe this to gravitational lens magnification. Similarly, SN CLN12Did is ∼0.2 ± 0.2 mag brighter than field SNe Ia. We derive independent estimates of the predicted magnification from CLASH strong+weak-lensing maps of the clusters (in magnitude units, 2.5 log{sub 10}μ): 0.83 ± 0.16 mag for SN CLO12Car, 0.28 ± 0.08 mag for SN CLN12Did, and 0.43 ± 0.11 mag for SN CLA11Tib. The two SNe Ia provide a new test of the cluster lens model predictions: we find that the magnifications based on the SN Ia brightness and those predicted by the lens maps are consistent. Our results herald the promise of future observations of samples of cluster-lensed SNe Ia (from the ground or space) to help illuminate the dark-matter distribution in clusters of galaxies, through the direct determination of absolute magnifications.« less

Three Gravitationally Lensed Supernovae Behind Clash Galaxy Clusters

NASA Technical Reports Server (NTRS)

Patel, Brandon; McCully, Curtis; Jha, Saurbh W.; Rodney, Steven A.; Jones, David O.; Graur, Or; Merten, Julian; Zitrin, Adi; Riess, Adam G.; Matheson, Thomas;

Improving consensus structure by eliminating averaging artifacts

PubMed Central

KC, Dukka B

2009-01-01

Background Common structural biology methods (i.e., NMR and molecular dynamics) often produce ensembles of molecular structures. Consequently, averaging of 3D coordinates of molecular structures (proteins and RNA) is a frequent approach to obtain a consensus structure that is representative of the ensemble. However, when the structures are averaged, artifacts can result in unrealistic local geometries, including unphysical bond lengths and angles. Results Herein, we describe a method to derive representative structures while limiting the number of artifacts. Our approach is based on a Monte Carlo simulation technique that drives a starting structure (an extended or a 'close-by' structure) towards the 'averaged structure' using a harmonic pseudo energy function. To assess the performance of the algorithm, we applied our approach to Cα models of 1364 proteins generated by the TASSER structure prediction algorithm. The average RMSD of the refined model from the native structure for the set becomes worse by a mere 0.08 Å compared to the average RMSD of the averaged structures from the native structure (3.28 Å for refined structures and 3.36 A for the averaged structures). However, the percentage of atoms involved in clashes is greatly reduced (from 63% to 1%); in fact, the majority of the refined proteins had zero clashes. Moreover, a small number (38) of refined structures resulted in lower RMSD to the native protein versus the averaged structure. Finally, compared to PULCHRA [1], our approach produces representative structure of similar RMSD quality, but with much fewer clashes. Conclusion The benchmarking results demonstrate that our approach for removing averaging artifacts can be very beneficial for the structural biology community. Furthermore, the same approach can be applied to almost any problem where averaging of 3D coordinates is performed. Namely, structure averaging is also commonly performed in RNA secondary prediction [2], which could also benefit from our approach. PMID:19267905

Quantitative structure-activity relationship of organosulphur compounds as soybean 15-lipoxygenase inhibitors using CoMFA and CoMSIA.

PubMed

Caballero, Julio; Fernández, Michael; Coll, Deysma

2010-12-01

Three-dimensional quantitative structure-activity relationship studies were carried out on a series of 28 organosulphur compounds as 15-lipoxygenase inhibitors using comparative molecular field analysis and comparative molecular similarity indices analysis. Quantitative information on structure-activity relationships is provided for further rational development and direction of selective synthesis. All models were carried out over a training set including 22 compounds. The best comparative molecular field analysis model only included steric field and had a good Q² = 0.789. Comparative molecular similarity indices analysis overcame the comparative molecular field analysis results: the best comparative molecular similarity indices analysis model also only included steric field and had a Q² = 0.894. In addition, this model predicted adequately the compounds contained in the test set. Furthermore, plots of steric comparative molecular similarity indices analysis field allowed conclusions to be drawn for the choice of suitable inhibitors. In this sense, our model should prove useful in future 15-lipoxygenase inhibitor design studies. © 2010 John Wiley & Sons A/S.

Microscopic Description of Thermodynamics of Lipid Membrane at Liquid-Gel Phase Transition

NASA Astrophysics Data System (ADS)

Kheyfets, B.; Galimzyanov, T.; Mukhin, S.

2018-05-01

A microscopic model of the lipid membrane is constructed that provides analytically tractable description of the physical mechanism of the first order liquid-gel phase transition. We demonstrate that liquid-gel phase transition is cooperative effect of the three major interactions: inter-lipid van der Waals attraction, steric repulsion and hydrophobic tension. The model explicitly shows that temperature-dependent inter-lipid steric repulsion switches the system from liquid to gel phase when the temperature decreases. The switching manifests itself in the increase of lateral compressibility of the lipids as the temperature decreases, making phase with smaller area more preferable below the transition temperature. The model gives qualitatively correct picture of abrupt change at transition temperature of the area per lipid, membrane thickness and volume per hydrocarbon group in the lipid chains. The calculated dependence of phase transition temperature on lipid chain length is in quantitative agreement with experimental data. Steric repulsion between the lipid molecules is shown to be the only driver of the phase transition, as van der Waals attraction and hydrophobic tension are weakly temperature dependent.

Mixed valency and site-preference chemistry for cerium and its compounds: A predictive density-functional theory study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alam, Aftab; Johnson, Duane D.

Cerium and its technologically relevant compounds are examples of anomalous mixed valency, originating from two competing oxidation states—itinerant Ce4+ and localized Ce3+. Under applied stress, anomalous transitions are observed but not well understood. Here we treat mixed valency as an “alloy” problem involving two valences with competing and numerous site-occupancy configurations. We use density-functional theory with Hubbard U (i.e., DFT+U) to evaluate the effective valence and predict properties, including controlling the valence by pseudoternary alloying. For Ce and its compounds, such as (Ce,La)2(Fe,Co)14B permanent magnets, we find a stable mixed-valent α state near the spectroscopic value of νs=3.53. Ce valencymore » in compounds depends on its steric volume and local chemistry. For La doping, Ce valency shifts towards γ-like Ce3+, as expected from steric volume; for Co doping, valency depends on local Ce-site chemistry and steric volume. Our approach captures the key origins of anomalous valency and site-preference chemistry in complex compounds.« less

Retinal Photoisomerization in Rhodopsin: Electrostatic and Steric Catalysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomasello, Gaia; Altoe, Piero; Stenta, Marco

2007-12-26

Excited state QM(CASPT2//CASSCF)/MM(GAFF) calculations, by our recently developed code COBRAMM (Computations at Bologna Relating Ab-initio and Molecular Mechanic Methods), were carried out in rhodopsin to investigate on the steric and electrostatic effects in retinal photoisomerization catalysis due to the {beta}-ionone ring and glutammate 181 (GLU 181), respectively. The excited state photoisomerization channel has been mapped and a new christallographyc structure (2.2 Aa resolution) has been used for this purpose. Two different set-ups have been used to evaluate the electrostatic effects of GLU 181 (which is very close to the central double bond of the chromophore): the first with a neutralmore » GLU 181 (as commonly accepted), the second with a negatively charged (i.e. deprotonated) GLU 181 (as very recent experimental findings seem to suggest). On the other hand, {beta}-ionone ring steric effects were evaluated by calculating the photoisomerization path of a modified chromophore, where the ring double bond has been saturated. Spectroscopic properties were calculated and compared with the available experimental data.« less

Internal gravity wave contributions to global sea surface variability

NASA Astrophysics Data System (ADS)

Savage, A.; Arbic, B. K.; Richman, J. G.; Shriver, J. F.; Buijsman, M. C.; Zamudio, L.; Wallcraft, A. J.; Sharma, H.

2016-02-01

High-resolution (1/12th and 1/25th degree) 41-layer simulations of the HYbrid Coordinate Ocean Model (HYCOM), forced by both atmospheric fields and the astronomical tidal potential, are used to construct global maps of sea-surface height (SSH). The HYCOM output has been separated into steric, non-steric, and total sea-surface height and the maps display variance in subtidal, tidal, and supertidal bands. Two of the global maps are of particular interest in planning for the upcoming Surface Water and Ocean Topography (SWOT) wide-swath satellite altimeter mission; (1) a map of the nonstationary tidal signal (estimated after removing the stationary tidal signal via harmonic analysis), and (2) a map of the steric supertidal contributions, which are dominated by the internal gravity wave continuum. Both of these maps display signals of order 1 cm2, the target accuracy for the SWOT mission. Therefore, both non-stationary internal tides and non-tidal internal gravity waves are likely to be important sources of "noise" that must be accurately removed before examination of lower-frequency phenomena can take place.

Steric interactions lead to collective tilting motion in the ribosome during mRNA-tRNA translocation

NASA Astrophysics Data System (ADS)

Nguyen, Kien; Whitford, Paul C.

2016-02-01

Translocation of mRNA and tRNA through the ribosome is associated with large-scale rearrangements of the head domain in the 30S ribosomal subunit. To elucidate the relationship between 30S head dynamics and mRNA-tRNA displacement, we apply molecular dynamics simulations using an all-atom structure-based model. Here we provide a statistical analysis of 250 spontaneous transitions between the A/P-P/E and P/P-E/E ensembles. Consistent with structural studies, the ribosome samples a chimeric ap/P-pe/E intermediate, where the 30S head is rotated ~18°. It then transiently populates a previously unreported intermediate ensemble, which is characterized by a ~10° tilt of the head. To identify the origins of head tilting, we analyse 781 additional simulations in which specific steric features are perturbed. These calculations show that head tilting may be attributed to specific steric interactions between tRNA and the 30S subunit (PE loop and protein S13). Taken together, this study demonstrates how molecular structure can give rise to large-scale collective rearrangements.

Diazo Reagents with Small Steric Footprints for Simultaneous Arming/SAR Studies of Alcohol-Containing Natural Products via O–H Insertion

PubMed Central

Chamni, Supakarn; He, Qing-Li; Dang, Yongjun; Bhat, Shridhar; Liu, Jun O.; Romo, Daniel

2011-01-01

Natural products are essential tools for basic cellular studies leading to the identification of medically relevant protein targets and the discovery of potential therapeutic leads. The development of methods that enable mild and selective derivatization of natural products continues to be of significant interest for mining their information-rich content. Herein, we describe novel diazo reagents for simultaneous arming and structure-activity relationship (SAR) studies of alcohol-containing natural products with a small steric footprint, namely an α-trifluoroethyl (HTFB) substituted reagent. The Rh(II)-catalyzed O–H insertion reaction of several natural products, including the potent translation inhibitor lactimidomycin, was investigated and useful reactivity and both chemo- and site (chemosite) selectivities were observed. Differential binding to the known protein targets of both FK506 and fumagillol was demonstrated, validating the advantage of the smaller steric footprint of trifluoroethyl derivatives. A p-azidophenyl diazo reagent is also described that will prove useful for photoaffinity labeling of low affinity small molecule protein receptors. PMID:21894934

CLASH: Joint analysis of strong-lensing, weak-lensing shear, and magnification data for 20 galaxy clusters*

DOE PAGES

Umetsu, Keiichi; Zitrin, Adi; Gruen, Daniel; ...

2016-04-20

Here, we present a comprehensive analysis of strong-lensing, weak-lensing shear and magnification data for a sample of 16 X-ray-regular and 4 high-magnification galaxy clusters atmore » $$0.19\\lesssim z\\lesssim 0.69$$ selected from Cluster Lensing And Supernova survey with Hubble (CLASH). Our analysis combines constraints from 16-band Hubble Space Telescope observations and wide-field multi-color imaging taken primarily with Suprime-Cam on the Subaru Telescope, spanning a wide range of cluster radii (10''–16'). We reconstruct surface mass density profiles of individual clusters from a joint analysis of the full lensing constraints, and determine masses and concentrations for all of the clusters. We find the internal consistency of the ensemble mass calibration to be ≤5% ± 6% in the one-halo regime (200–2000 kpc h –1) compared to the CLASH weak-lensing-only measurements of Umetsu et al. For the X-ray-selected subsample of 16 clusters, we examine the concentration–mass (c–M) relation and its intrinsic scatter using a Bayesian regression approach. Our model yields a mean concentration of $$c{| }_{z=0.34}=3.95\\pm 0.35$$ at M200c sime 14 × 1014 M⊙ and an intrinsic scatter of $$\\sigma (\\mathrm{ln}{c}_{200{\\rm{c}}})=0.13\\pm 0.06$$, which is in excellent agreement with Λ cold dark matter predictions when the CLASH selection function based on X-ray morphological regularity and the projection effects are taken into account. We also derive an ensemble-averaged surface mass density profile for the X-ray-selected subsample by stacking their individual profiles. The stacked lensing signal is detected at 33σ significance over the entire radial range ≤4000 kpc h –1, accounting for the effects of intrinsic profile variations and uncorrelated large-scale structure along the line of sight. The stacked mass profile is well described by a family of density profiles predicted for cuspy dark-matter-dominated halos in gravitational equilibrium, namely, the Navarro–Frenk–White (NFW), Einasto, and DARKexp models, whereas the single power-law, cored isothermal and Burkert density profiles are disfavored by the data. We show that cuspy halo models that include the large-scale two-halo term provide improved agreement with the data. For the NFW halo model, we measure a mean concentration of $${c}_{200{\\rm{c}}}={3.79}_{-0.28}^{+0.30}$$ at $${M}_{200{\\rm{c}}}={14.1}_{-1.0}^{+1.0}\\times {10}^{14}\\;{M}_{\\odot }$$, demonstrating consistency between the complementary analysis methods.« less

Optical properties and progressive sterical hindering in pyridinium phenoxides

NASA Astrophysics Data System (ADS)

Boeglin, A.; Barsella, A.; Fort, A.; Mançois, F.; Rodriguez, V.; Diemer, V.; Chaumeil, H.; Defoin, A.; Jacques, P.; Carré, C.

2007-07-01

Pyridinium phenoxides are model compounds associating large dipole moments with high optical nonlinearities. A progression of sterically hindered forms of such zwitterions has been synthesized in order to investigate their structure/property relationships. Their UV-vis absorption in acetonitrile has been analyzed as a function of concentration in order to assess the presence of aggregates and the level of protonation. The quadratic optical properties have been measured by the EFISH and hyper-Rayleigh techniques and are interpreted via semi-empirical calculations. The solvation model used leads to results that agree with our experimental findings indicating an increased response for intermediate twist angles.

Correction: β-Amyrin synthase from Euphorbia tirucalli L. functional analyses of the highly conserved aromatic residues Phe413, Tyr259 and Trp257 disclose the importance of the appropriate steric bulk, and cation-π and CH-π interactions for the efficient catalytic action of the polyolefin cyclization cascade.

PubMed

Ito, Ryousuke; Nakada, Chika; Hoshino, Tsutomu

2017-01-18

Correction for 'β-Amyrin synthase from Euphorbia tirucalli L. functional analyses of the highly conserved aromatic residues Phe413, Tyr259 and Trp257 disclose the importance of the appropriate steric bulk, and cation-π and CH-π interactions for the efficient catalytic action of the polyolefin cyclization cascade' by Ryousuke Ito et al., Org. Biomol. Chem., 2017, 15, 177-188.

Discovering the balance of steric and electronic factors needed to provide a new structural motif for photocatalytic hydrogen production from water.

PubMed

White, Travis A; Whitaker, Brittany N; Brewer, Karen J

2011-10-05

Ru,Rh,Ru supramolecules are known to undergo multielectron photoreduction and reduce H(2)O to H(2). Ru,Rh bimetallics were recently shown to photoreduce but not catalyze H(2)O reduction. Careful tuning of sterics and electronics for [(TL)(2)Ru(dpp)RhCl(2)(TL')](3+) produce active bimetallic photocatalysts (TL = terminal ligand). The system with TL,TL' = Ph(2)phen photocatalytically reduces H(2)O to H(2) while TL,TL' = phen,bpy or bpy,(t)Bu(2)bpy do not.

Publication visibility of sensitive public health data: when scientists bury their results.

PubMed

Rier, David A

2004-10-01

What happens when the scientific tradition of openness clashes with potential societal risks? The work of American toxic-exposure epidemiologists can attract media coverage and lead the public to change health practices, initiate lawsuits, or take other steps a study's authors might consider unwarranted. This paper, reporting data from 61 semi-structured interviews with U.S. toxic-exposure epidemiologists, examines whether such possibilities shaped epidemiologists' selection of journals for potentially sensitive papers. Respondents manifested strong support for the norm of scientific openness, but a significant minority had or would/might, given the right circumstances, publish sensitive data in less visible journals, so as to prevent unwanted media or public attention. Often, even those advocating such limited "burial" upheld openness, claiming that less visible publication allowed them to avoid totally withholding the data from publication. However, 15% of the sample had or would, for the most sensitive types of data, withhold publication altogether. Rather than respondents explaining their actions in terms of an expected split between "pure science" and "social advocacy" models, even those publishing in the more visible journals often described their actions in terms of their "responsibility". Several practical limitations (particularly involving broader access to scientific literature via the Internet) of the strategy of burial are discussed, and some recommendations are offered for scientists, the media, and the public.

Comics and War: Transforming Perceptions of the Other through a Constructive Learning Experience

ERIC Educational Resources Information Center

Jorenby, Marnie K.

2007-01-01

During World War II the United States and Japan experienced what Rouhana and Bar-Tal described as "a clash of narratives between two societies". The Japanese envisioned themselves as heroes saving Asia from western colonisation, while the Americans felt the need to defend the West from the "Yellow Peril". In the research…

Outward Peace, Inward Pieces: A Case of the Effect of the Kenya Post-Election Violence

ERIC Educational Resources Information Center

Ochieng', Josephine Atieno

2010-01-01

In December 2007, unprecedented violence erupted in Kenya following the announcement of disputed presidential election results. The electorate was divided along ethnic lines and tribal clashes bordering on ethnic cleansing escalated. Those supporting opposing camps found themselves on the wrong side of the political divide leading to killings,…

A Convergent Parallel Mixed-Methods Study of Controversial Issues in Social Studies Classes: A Clash of Ideologies

ERIC Educational Resources Information Center

Demir, Selcuk Besir; Pismek, Nuray

2018-01-01

In today's educational landscape, social studies classes are characterized by controversial issues (CIs) that teachers handle differently using various ideologies. These CIs have become more and more popular, particularly in heterogeneous communities. The actual classroom practices for teaching social studies courses are unclear in the context of…

Failing at College Football Reform: The Jan Kemp Trial at the University of Georgia

ERIC Educational Resources Information Center

Fulford, Michael J.

2008-01-01

Throughout the history of college football, there have been efforts to reform the system and stop improprieties, yet conflict between gaining academic and athletic prowess at colleges remained a central theme. In the 1980s, the Jan Kemp trial involving the University of Georgia demonstrated this clash between revenue-generating athletics and…

Creating More "Elbow Room" for Collaborative Reflective Practice in the Competitive, Performative Culture of Today's University

ERIC Educational Resources Information Center

Kennelly, Robert; McCormack, Coralie

2015-01-01

We live in "a world of clashing interests" [Zinn, H. (1991). "Declarations of independence: Cross-examining American ideology." Toronto: Harper Collins, p. xx]. In a grapple for survival, universities choose to spend less money and time on teaching and learning, less time on robust evaluation of student learning and…

Raising Cain: The University Student and the Politics of Protest

ERIC Educational Resources Information Center

Hundscheid, John

2010-01-01

Student protests and occupations are not new phenomena. On February 10, 1355, what came to be known as the St. Scholastica Day riot occurred. Oxford students and townspeople clashed after a dispute in a local tavern and almost one hundred people were killed. But while student protests have occurred throughout history, the 1960s introduced a new…

Digitizing a Heritage of Faded Memories: A Case Study on Extending Historical Research Capabilities

ERIC Educational Resources Information Center

Branting, Steven D.

2009-01-01

A historical fact is like a fata morgana, "always less than what really happened." Even consensus does not establish truth; otherwise history is merely the version of the past that people agree to accept. The students who participated in the acclaimed 5th Street Cemetery Necrogeographical Study innocently found themselves clashing with…

A Critical Exploration of "Working Together, Learning Together"--Does It Meet the Learning Needs of Nurses?

ERIC Educational Resources Information Center

Walshe, Amanda

2003-01-01

Using an educational ideology and curriculum design perspective, a British initiative to promote nurses' lifelong learning was analyzed. The program creates a clash between romanticist and revisionist ideology. From the perspective of Beattie's fourfold curriculum model, it fails to acknowledge the uniqueness of nursing knowledge, the field's…

Fred Hoyle

NASA Astrophysics Data System (ADS)

Mitton, Simon

2011-02-01

Foreword Paul Davies; Prologue; 1. An end and a beginning; 2. Training for cosmology; 3. The star makers; 4. Hoyle's secret war; 5. The nature of the Universe; 6. Lives of the stars; 7. Clash of Titans; 8. Origin of the chemical elements; 9. Matters of gravity; 10. Mountains to climb; 11. The watershed; 12. Stones, bones, bugs and accidents; Acknowledgements; Notes; Bibliography; Index.

When Cultures Clash: The Story of One School's Journey from Acculturation to Understanding

ERIC Educational Resources Information Center

Heinrich, Jill

2018-01-01

This qualitative case study examines the conflicts and challenges that one American junior high school experienced when a substantial number of African-American families migrated to the community from Chicago to secure Section 8 housing; their housing projects had recently been felled through the auspices of HOPE VI (Housing Opportunities for…

The Higher Education System in Mexico at the Threshold of Change

ERIC Educational Resources Information Center

Varela, Gonzalo

2006-01-01

Education in Mexico wants restructuring since the signing of the North America Free Trade Agreement (NAFTA) by Canada, Mexico and the United States in 1994. In higher education, a new policy has been adopted to increase the enrollment, but a simultaneous improvement in quality is also needed. Nevertheless it clashes with old academic structures.…

Bridging the Gap in Expectations between International Students and Academic Staff

ERIC Educational Resources Information Center

Kingston, Emma; Forland, Heather

2008-01-01

This article is concerned with the transition into higher education in the United Kingdom of students with an East Asian background. Such a fusion of cultures (the Western individualist culture and East Asian collectivist culture) often creates a clash of traditions. The tensions that arise between the expectations of the most rapidly growing…

On Cioran's Criticism of Utopian Thinking and the History of Education

ERIC Educational Resources Information Center

Vanobbergen, Bruno; Smeyers, Paul

2007-01-01

The starting point of our research is the recent discussion within history of education about the aim and scope of historical educational research. More specifically, it deals with the relationship between the past and the future and is characterized by two clashing paradigms. The recent discussion within history of education is from the…

U.S. v. "Providence Journal": The First Amendment and the Constitutionality of Enforcing Unconstitutional Orders.

ERIC Educational Resources Information Center

Labunski, Richard

Serious constitutional problems arise when the contempt power of judges clashes with other compelling interests such as those of the First Amendment. The "collateral bar" rule--which requires that court orders, even those later determined to be unconstitutional, must be complied with until amended or vacated--in effect, calls for…

"Flexible Work Arrangements: Managing the Work-Family Boundary" by B. Gottlieb, E. K. Kelloway, and E. Barham. Book Review.

ERIC Educational Resources Information Center

Daly, Kerry

1999-01-01

Finds that Gottlieb et al.'s work provides an excellent overview of flexible work arrangements in a variety of work organizations for managers, human-resources professionals, and employees. Considers the work an excellent primer presenting useful information about alternative work arrangements, factors involved in work/family clashes,…

CLASH! Superheroic yet Sensible Strategies for Teaching the New Literacies Despite the Status Quo

ERIC Educational Resources Information Center

Vavra, Sandra, Ed.; Spencer, Sharon L., Ed.

2011-01-01

This book offers ideas that secondary teachers, university content faculty, and teacher educators can use to challenge traditional literacy practices and demonstrate creative, innovative ways of incorporating new literacies into the classroom, all within a strong theoretical framework. Teachers are trying to catch up to the new challenges of the…

Intergenerational Cultural Dissonance, Parent-Child Conflict and Bonding, and Youth Problem Behaviors among Vietnamese and Cambodian Immigrant Families

ERIC Educational Resources Information Center

Choi, Yoonsun; He, Michael; Harachi, Tracy W.

2008-01-01

Intergenerational cultural dissonance (ICD)--a clash between parents and children over cultural values--is a frequent issue for Asian American youth. Using longitudinal data from the Cross Cultural Families Project, this study examines the mechanisms by which ICD contributes to problem behaviors, including whether ICD predicts parent-child…

A Technological Determinist Viewpoint of the Stanton-Staggers Conflict over "The Selling of the Pentagon": Print Man Versus Electronic Man.

ERIC Educational Resources Information Center

Breen, Myles P.

Media, specifically documentary films on television, profoundly affect both social structure and man's psychological percepts. The clash of views depicted is between "print man" (using U.S. Representative Harley Staggers as an example) and "electronic man" (portrayed as Frank Stanton of CBS) centering on Stagger's objections to…

Clash! The World of Debate

ERIC Educational Resources Information Center

Azzam, Amy M.

2008-01-01

Debating has been around for a long time, with some pretty spectacular results. Look at Socrates, who was put to death in 399 BCE for corrupting the youth of Athens; his accusers could not forgive him for incessantly questioning their beliefs and making "the worse appear the better cause." More recently, debating has morphed into a sport for the…

Fiction for Adolescent and Young Adult Readers from Longacre Press, New Zealand.

ERIC Educational Resources Information Center

Nixon, Helen; Comber, Barbara

2001-01-01

Explores fiction for adolescents and young adults published by Longacre Press, New Zealand, a small independent publishing house founded in 1994. Notes teenage fiction is a specialist area of this publisher although they also publish general nonfiction, historical, and art books. Discusses works published in the themes of clashes and coping,…

Science, Innovation, and Social Work: Purpose: Clash or Convergence?

ERIC Educational Resources Information Center

Flynn, Marilyn L.

2017-01-01

Social work as a human services profession has been distinctive for its inclusion of research as a required element of practice and instrument in instigating reform. At the present time, the relationship of social work to science and a redefinition of social work as a science have reentered our national dialogue with new force. This expansion of…

Free Speech vs. Free Enterprise: The Public Policy Clash between the First Amendment and the Right of Publicity.

ERIC Educational Resources Information Center

LeBlanc-Wicks, Jan

Intended to help clarify issues surrounding the right of publicity (protection against the unauthorized commercial appropriation of a person's name, likeness, achievements or characteristics), this paper provides explanations of how the right developed, what it protects, how it has been applied in various jurisdictions around the country, and the…

Dialogue on Dialogue on Dialogic Pedagogy

ERIC Educational Resources Information Center

Sullivan, Paul

2014-01-01

It appears that in September, 2011, Rome experienced much more than a dialogue on dialogic pedagogy but a gladiatorial clash of personalities and ideas. Heat, we are told, was generated (above, p.1) and in the dissipation of this heat on to the page, even the reader gets hot and flushed. We are told that arguments "fail" (above, p.16);…

Visual Messages: Integrating Imagery into Instruction. A Teacher Resource for Media and Visual Literacy.

ERIC Educational Resources Information Center

Considine, David M.; Haley, Gail E.

This book argues that people live simultaneously in two different cultures. Values of the first culture are imparted to children through curriculum in the nation's public school classrooms. The second culture is the world of mass communication that promotes consumption, instant gratification, and impulse. The clash between these cultures confronts…

Chinua Achebe's "Things Fall Apart": Oral and Literary Strategies. [Lesson Plan].

ERIC Educational Resources Information Center

2002

Chinua Achebe is one of Africa's best-known contemporary writers. His first novel, "Things Fall Apart," deals with the clash of cultures and the violent transitions in life and values brought about by the onset of British colonialism in Nigeria at the end of the 19th century. Published in 1958, just before Nigerian independence, the…

The Role of Historical-Philosophical Controversies in Teaching Sciences: The Debate between Biot and Ampere

ERIC Educational Resources Information Center

Braga, Marco; Guerra, Andreia; Reis, Jose Claudio

2012-01-01

This paper evaluates the viability of using controversies in teaching. An educational project has been elaborated in which some historical-philosophical clashes were introduced into the classical syllabus of physics. The historical-philosophical controversy dealt with here, took place between the French physicists Biot and Ampere in the 19th…

Film Choices for Screening Literacy: The "Pygmalion Template" in the Curriculum as Contact Zone

ERIC Educational Resources Information Center

Verdoodt, Ive; Rutten, Kris; Soetaert, Ronald; Mottart, Andre

2010-01-01

This study discusses the representation of (the) literacy (myth) in popular movies and a teaching and research project on cinematic literacy narratives. It attempts to reveal the existence of a powerful 'Pygmalion template' in contemporary movie culture. Focusing on a discourse or culture clash 'Pygmalion movies' simultaneously contribute to the…

Sudanese Images of the Other: Education and Conflict in Sudan

ERIC Educational Resources Information Center

Breidlid, Anders

2010-01-01

Education can contribute to peace and reconciliation as well as to conflict and strife. The complex, often contradictory role of education in conflict is explored in this article in relation to Sudan. The focus of the article is the North-South conflict, bearing in mind that other, "minor" wars and military clashes in both the North and…

U.S. Spanish and Education: Global and Local Intersections

ERIC Educational Resources Information Center

García, Ofelia

2014-01-01

The author of this chapter argues that the failure of Spanish language education policies in the United States to educate both Latinos and non-Latinos has to do with the clash between three positions--(a) the English language, characterized by U.S. educational authorities as the unique and powerful lingua franca; (b) the Spanish language, as…

Sex Education, Liberalism, and Natural Law: Toward an Overlapping Consensus.

ERIC Educational Resources Information Center

D'Onofrio, Eve

From a political standpoint, the battle over sexuality education is not simply a dispute over the most effective means to promote the sexual and reproductive health of youth; but rather, a clash over the shape and direction of society itself. (McKay, 1999). This paper explores the theoretical underpinnings of the debate over the content and scope…

Civil-Military Relations and Militarization in El Salvador

DTIC Science & Technology

2015-03-01

6  C.  DISCUSSION ...................................................................................................7  II.  HISTORY OF THE...explains the metrics by which militarization in El Salvador is to be assessed. Chapter II presents the history of civil-military relations and...militarization in El Salvador up to 2009. Salvadoran history , not unlike other histories , is a clash of perspectives of the peasantry, military, guerrillas

Baby Boomers in an Active Adult Retirement Community: Comity Interrupted

ERIC Educational Resources Information Center

Roth, Erin G.; Keimig, Lynn; Rubinstein, Robert L.; Morgan, Leslie; Eckert, J. Kevin; Goldman, Susan; Peeples, Amanda D.

2012-01-01

Purpose of the Study: This article explores a clash between incoming Baby Boomers and older residents in an active adult retirement community (AARC). We examine issues of social identity and attitudes as these groups encounter each other. Design and Methods: Data are drawn from a multiyear ethnographic study of social relations in senior housing.…

Cultural Factors in Collegiate Eating Disorder Pathology: When Family Culture Clashes with Individual Culture

ERIC Educational Resources Information Center

Tomiyama, A. Janet; Mann, Traci

2008-01-01

Objective: The authors evaluated the validity of familial enmeshment (extreme proximity in family relationships) as a risk factor for eating disorders across cultural value orientations. They tested the hypothesis that although familial enmeshment may be a risk factor for eating disorder pathology for (1) participants of non-Asian descent or (2)…

Collaborating with Parents of Students with Disabilities

ERIC Educational Resources Information Center

Cianca, Marie; Wischnowski, Michael

2012-01-01

Many Hollywood films show the struggles of students with disabilities. More often than not, the struggle involves a clash between family and school. Real life shows that the movies have some of it right. According to MetLife's 2005 Survey of the American Teacher, new teachers often consider working with parents to be their biggest challenge. Both…

Complex Interplays: Teacher and Students' Co-Construction of New Media Classroom Spaces

ERIC Educational Resources Information Center

Rust, Julie

2013-01-01

Although increasingly encouraged to incorporate new media into classrooms to prepare students for engaged participation in a digital world, teachers are often taken by surprise when paradigm clashes arise between traditional school expectations and the affordances of these new spaces. Students, at the same time, are faced with making sense of the…

Culture Clash: Interactions between Afrocultural and Mainstream Cultural Styles in Classrooms Serving African American Students

ERIC Educational Resources Information Center

Rouland, Karmen; Matthews, Jamaal S.; Byrd, Christy M.; Meyer, Rika M. L.; Rowley, Stephanie J.

2014-01-01

This study examined the relation between classroom cultural and achievement-related characteristics and their influence on social outcomes in a sample of 74 fifth grade African American youth (41 girls; 33 boys) ages 10-13 years. Trained observers rated classrooms according to Boykin's (Boykin, Tyler, & Miller, 2005) definition of mainstream…

Educating School Leaders for Democracy

ERIC Educational Resources Information Center

Moos, Lejf

2010-01-01

In order to be able to discuss, in meaningful ways, how school leaders should be educated one needs to sketch the context in which they are going to lead, that is the visions and purpose of education and the schooling, which is dominant in society. In most societies one sees clashes of many discourses and cultural/political fights. In order to…

Student Teachers' and Mentor Teachers' Perceptions and Expectations of a Mentoring Relationship: Do They Match or Clash?

ERIC Educational Resources Information Center

Izadinia, Mahsa

2016-01-01

This study examines similarities and differences between mentor teachers' and student teachers' perceptions of the components of a positive mentoring relationship and its impact on the identity formation of student teachers. In addition to the interview data, the participants were asked to use metaphors to describe the mentoring relationship. The…

Exonuclease III-Assisted Upconversion Resonance Energy Transfer in a Wash-Free Suspension DNA Assay.

PubMed

Chen, Yinghui; Duong, Hien T T; Wen, Shihui; Mi, Chao; Zhou, Yingzhu; Shimoni, Olga; Valenzuela, Stella M; Jin, Dayong

2018-01-02

Sensitivity is the key in optical detection of low-abundant analytes, such as circulating RNA or DNA. The enzyme Exonuclease III (Exo III) is a useful tool in this regard; its ability to recycle target DNA molecules results in markedly improved detection sensitivity. Lower limits of detection may be further achieved if the detection background of autofluorescence can be removed. Here we report an ultrasensitive and specific method to quantify trace amounts of DNA analytes in a wash-free suspension assay. In the presence of target DNA, the Exo III recycles the target DNA by selectively digesting the dye-tagged sequence-matched probe DNA strand only, so that the amount of free dye removed from the probe DNA is proportional to the number of target DNAs. Remaining intact probe DNAs are then bound onto upconversion nanoparticles (energy donor), which allows for upconversion luminescence resonance energy transfer (LRET) that can be used to quantify the difference between the free dye and tagged dye (energy acceptor). This scheme simply avoids both autofluorescence under infrared excitation and many tedious washing steps, as the free dye molecules are physically located away from the nanoparticle surface, and as such they remain "dark" in suspension. Compared to alternative approaches requiring enzyme-assisted amplification on the nanoparticle surface, introduction of probe DNAs onto nanoparticles only after DNA hybridization and signal amplification steps effectively avoids steric hindrance. Via this approach, we have achieved a detection limit of 15 pM in LRET assays of human immunodeficiency viral DNA.

Steric sea level variability (1993-2010) in an ensemble of ocean reanalyses and objective analyses

NASA Astrophysics Data System (ADS)

Storto, Andrea; Masina, Simona; Balmaseda, Magdalena; Guinehut, Stéphanie; Xue, Yan; Szekely, Tanguy; Fukumori, Ichiro; Forget, Gael; Chang, You-Soon; Good, Simon A.; Köhl, Armin; Vernieres, Guillaume; Ferry, Nicolas; Peterson, K. Andrew; Behringer, David; Ishii, Masayoshi; Masuda, Shuhei; Fujii, Yosuke; Toyoda, Takahiro; Yin, Yonghong; Valdivieso, Maria; Barnier, Bernard; Boyer, Tim; Lee, Tony; Gourrion, Jérome; Wang, Ou; Heimback, Patrick; Rosati, Anthony; Kovach, Robin; Hernandez, Fabrice; Martin, Matthew J.; Kamachi, Masafumi; Kuragano, Tsurane; Mogensen, Kristian; Alves, Oscar; Haines, Keith; Wang, Xiaochun

2017-08-01

Quantifying the effect of the seawater density changes on sea level variability is of crucial importance for climate change studies, as the sea level cumulative rise can be regarded as both an important climate change indicator and a possible danger for human activities in coastal areas. In this work, as part of the Ocean Reanalysis Intercomparison Project, the global and regional steric sea level changes are estimated and compared from an ensemble of 16 ocean reanalyses and 4 objective analyses. These estimates are initially compared with a satellite-derived (altimetry minus gravimetry) dataset for a short period (2003-2010). The ensemble mean exhibits a significant high correlation at both global and regional scale, and the ensemble of ocean reanalyses outperforms that of objective analyses, in particular in the Southern Ocean. The reanalysis ensemble mean thus represents a valuable tool for further analyses, although large uncertainties remain for the inter-annual trends. Within the extended intercomparison period that spans the altimetry era (1993-2010), we find that the ensemble of reanalyses and objective analyses are in good agreement, and both detect a trend of the global steric sea level of 1.0 and 1.1 ± 0.05 mm/year, respectively. However, the spread among the products of the halosteric component trend exceeds the mean trend itself, questioning the reliability of its estimate. This is related to the scarcity of salinity observations before the Argo era. Furthermore, the impact of deep ocean layers is non-negligible on the steric sea level variability (22 and 12 % for the layers below 700 and 1500 m of depth, respectively), although the small deep ocean trends are not significant with respect to the products spread.

Direct access to highly crystalline mesoporous nano TiO2 using sterically bulky organic acid templates

NASA Astrophysics Data System (ADS)

Bakre, Pratibha V.; Tilve, S. G.

2018-05-01

Sterically bulky monocarboxylic acid templates pivalic acid and phenoxyacetic acid are reported for the first time as organic templates in the sol-gel synthesis of TiO2. Mesoporous nanoparticulates of pure anatase phase and of well defined size were synthesized. The characterization of the materials prepared was done by various methods such as XRD, SEM, TEM, FTIR, UV-DRS, BET, etc. The prepared TiO2 samples were evaluated for the day light photodegradation of methylene blue by comparing with Degussa P25 and templates free synthesized TiO2 and were found to be more efficient.

Restricted amide rotation with steric hindrance induced multiple conformations

NASA Astrophysics Data System (ADS)

Krishnan, V. V.; Vazquez, Salvador; Maitra, Kalyani; Maitra, Santanu

2017-12-01

The Csbnd N bond character is dependent directly upon the resonance-contributor structure population driven by the delocalized nitrogen lone-pair of electrons. In the case of N, N-dibenzyl-ortho-toluamide (o-DBET), the molecule adopts subpopulations of conformers with distinct NMR spectral features, particularly at low temperatures. This conformational adaptation is unique to o-DBET, while the corresponding meta- and para- forms do not show such behavior. Variable-temperature (VT) NMR, two-dimensional exchange spectroscopy (EXSY), and qualitative molecular modeling studies are used to demonstrate how multiple competing interactions such as restricted amide rotation and steric hindrance effects can lead to versatile molecular adaptations in the solution state.

Steric hindrance effects in the use of heterocyclic azodyestuffs as spectrophotometric reagents.

PubMed

Geary, W J; Bottomley, F

1967-05-01

The heterocyclic azo dyestuffs 4-(n-methyl-2 -pyridylazo)-resorcinol (where n = 3', 4', 5', 6') have been prepared, and their possible use as spectrophotometric reagents investigated. The dyestuffs are shown to function analogously to the parent ligand 4-(2'-pyridylazo) resorcinol (PAR) in giving red complexes with the ions Co(2+), Ni(2+), Cu(2+), Zn(2+) and UO(2)(2+). Steric effects resulting from the position of the methyl group in the heterocyclic ring are shown to occur in relation both to the spectra of the dyestuffs themselves and to the sensitivity of their reactions with the metal ions.

Total synthesis of (+/-)-taiwaniaquinol B via a domino intramolecular friedel-crafts acylation/carbonyl alpha-tert-alkylation reaction.

PubMed

Fillion, Eric; Fishlock, Dan

2005-09-28

The first synthesis of taiwaniaquinol B, a 6-nor-5(6-->7)abeoabietane-type diterpenoid exhibiting the uncommon fused 6-5-6 tricyclic carbon skeleton, was accomplished in 15 steps. A Lewis acid-promoted tandem intramolecular Friedel-Crafts/carbonyl alpha-tert-alkylation reaction was exploited as the core strategy for the synthesis of the sterically congested 1-indanone-containing tricyclic structure. This multiple carbon-carbon bond forming reaction exploits the unique reactivity of Meldrum's acid. The facile precursor synthesis makes this a useful methodology for the expedient modification and assembly of sterically congested 1-indanone-containing ring systems.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeno, Wade F.; Johnson, Kaitlin E.; Sasaki, Darryl Y.

We use fluorescence microscopy to examine the dynamics of the crowding-induced mixing transition of liquid ordered (L o)–liquid disordered (L d) phase separated lipid bilayers when the following particles of increasing size bind to either the L o or L d phase: Ubiquitin, green fluorescent protein (GFP), and nanolipoprotein particles (NLPs) of two diameters. These proteinaceous particles contained histidine-tags, which were phase targeted by binding to iminodiacetic acid (IDA) head groups, via a Cu 2+ chelating mechanism, of lipids that specifically partition into either the Lo phase or Ld phase. The degree of steric pressure was controlled by varying themore » size of the bound particle (10–240 kDa) and the amount of binding sites present (i.e., DPIDA concentrations of 9 and 12 mol%) in the supported lipid multibilayer platform used here. We develop a mass transfer-based diffusional model to analyze the observed L o phase domain dissolution that, along with visual observations and activation energy calculations, provides insight into the sequence of events in crowding-induced mixing. Furthermore, our results suggest that the degree of steric pressure and target phase influence not only the efficacy of steric-pressure induced mixing, but the rate and controlling mechanism for which it occurs.« less

Effect of the Molecular Configuration of Perylene Diimide Acceptors on Charge Transfer and Device Performance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qu, Jianfei; Mu, Zhao; Lai, Hanjian

Three perylene diimides (PDI)-based small molecules, T2-SePDI2, T3B-SePDI3, and T4B-SePDI4, with different molecular configurations are synthesized. Due to a large steric hindrance, the molecular configuration of T3B-SePDI3 is the most distorted, followed by T4BSePDI4, while T2-SePDI2 shows the smallest steric hindrance. Inverted bulk heterojunction solar cells based on T3B-SePDI3 and PBDB-T show the highest power conversion efficiency (PCE) of 5.82% with an open-circuit voltage of 0.98 V, a high short-circuit current density of 10.52 mA/cm2, and a fill factor of 56.31%. The PCEs of the T2-SePDI2- and T4B-SePDI4- based devices are 4.10% and 5.10%, respectively. Furthermore, the results demonstrate thatmore » the molecular configuration of the PDI-based small molecule acceptor is critical and that increasing the steric hindrance is helpful in suppressing aggregation and improving device performance.« less

Effect of the Molecular Configuration of Perylene Diimide Acceptors on Charge Transfer and Device Performance

DOE PAGES

Qu, Jianfei; Mu, Zhao; Lai, Hanjian; ...

2018-01-25

Three perylene diimides (PDI)-based small molecules, T2-SePDI2, T3B-SePDI3, and T4B-SePDI4, with different molecular configurations are synthesized. Due to a large steric hindrance, the molecular configuration of T3B-SePDI3 is the most distorted, followed by T4BSePDI4, while T2-SePDI2 shows the smallest steric hindrance. Inverted bulk heterojunction solar cells based on T3B-SePDI3 and PBDB-T show the highest power conversion efficiency (PCE) of 5.82% with an open-circuit voltage of 0.98 V, a high short-circuit current density of 10.52 mA/cm2, and a fill factor of 56.31%. The PCEs of the T2-SePDI2- and T4B-SePDI4- based devices are 4.10% and 5.10%, respectively. Furthermore, the results demonstrate thatmore » the molecular configuration of the PDI-based small molecule acceptor is critical and that increasing the steric hindrance is helpful in suppressing aggregation and improving device performance.« less

Conservation of direct dynamics in sterically hindered SN2/E2 reactions.

PubMed

Carrascosa, Eduardo; Meyer, Jennifer; Michaelsen, Tim; Stei, Martin; Wester, Roland

2018-01-21

Nucleophilic substitution (S N 2) and base-induced elimination (E2), two indispensable reactions in organic synthesis, are commonly assumed to proceed under stereospecific conditions. Understanding the way in which the reactants pre-orient in these reactions, that is its stereodynamics, is essential in order to achieve a detailed atomistic picture and control over such processes. Using crossed beam velocity map imaging, we study the effect of steric hindrance in reactions of Cl - and CN - with increasingly methylated alkyl iodides by monitoring the product ion energy and scattering angle. For both attacking anions the rebound mechanism, indicative of a direct S N 2 pathway, is found to contribute to the reaction at high relative collision energies despite being increasingly hindered. An additional forward scattering mechanism, ascribed to a direct E2 reaction, also contributes at these energies. Inspection of the product energy distributions confirms the direct and fast character of both mechanisms as opposed to an indirect reaction mechanism which leads to statistical energy redistribution in the reaction complex. This work demonstrates that nonstatistical dynamics and energetics govern S N 2 and E2 pathways even in sterically hindered exchange reaction systems.

Conservation of direct dynamics in sterically hindered SN2/E2 reactions

PubMed Central

Carrascosa, Eduardo; Meyer, Jennifer; Michaelsen, Tim; Stei, Martin

2017-01-01

Nucleophilic substitution (SN2) and base-induced elimination (E2), two indispensable reactions in organic synthesis, are commonly assumed to proceed under stereospecific conditions. Understanding the way in which the reactants pre-orient in these reactions, that is its stereodynamics, is essential in order to achieve a detailed atomistic picture and control over such processes. Using crossed beam velocity map imaging, we study the effect of steric hindrance in reactions of Cl– and CN– with increasingly methylated alkyl iodides by monitoring the product ion energy and scattering angle. For both attacking anions the rebound mechanism, indicative of a direct SN2 pathway, is found to contribute to the reaction at high relative collision energies despite being increasingly hindered. An additional forward scattering mechanism, ascribed to a direct E2 reaction, also contributes at these energies. Inspection of the product energy distributions confirms the direct and fast character of both mechanisms as opposed to an indirect reaction mechanism which leads to statistical energy redistribution in the reaction complex. This work demonstrates that nonstatistical dynamics and energetics govern SN2 and E2 pathways even in sterically hindered exchange reaction systems. PMID:29629138

Culture Clash: U.S. Television Programs in Korea.

ERIC Educational Resources Information Center

Kang, Jong Geun; Morgan, Michael

A study examined the influence that the United States media have on the values, morality, and traditions of other countries, and more specifically the effects on Korean values of American television as it is broadcast on the U.S. Forces Korean Network. College students in Seoul, Korea (46% male and 54% female with a mean age of 24.6) answered a…

Operation Exodus: The Massacre of 44 Philippine Police Commandos In Mamasapano Clash

DTIC Science & Technology

2016-09-01

strategic thinking, utilizing Game Theory and Multi-Attribute Decision Making; the combination of these two dynamic tools is used to evaluate their...thinking, utilizing Game Theory and Multi-Attribute Decision Making; the combination of these two dynamic tools is used to evaluate their potential...35 A. GAME THEORETIC APPROACH ......................................................36 B. APPLYING GAME THEORY TO OPLAN: EXODUS

Clash inside the Academy: The Market and the Strife for the Democratic Values of the Western University

ERIC Educational Resources Information Center

Gburi, Imad

2016-01-01

The growing popularity of the corporate university model raises the question of whether the market principles are suitable for planning the policy of a key enterprise like the university without weakening its capacity of pursuing critical knowledge and teaching for democracy. Does the inclusion of the free market imperatives in the functioning of…

Creating New Meanings in Leading Learning. Proceedings [of the] National Conference on Alternative and External Degree Programs for Adults (22nd, Pittsburgh, PA, October 9-12, 2002).

ERIC Educational Resources Information Center

American Council on Education, Washington, DC.

These proceedings are comprised of 25 presentations divided into 5 "tracks." Section I, Diversity and Social Justice, has "Free to Learn with Body and Soul Jazz Divas, Beat Poets, and Street Preachers" (Ferrante, Belcastro); "Clashing Cultures in Our Classrooms" (Gabrich, Rothenberger); "Encouraging Adults in…

Teachers' Rights versus Students' Rights: Race and Professional Authority in the New York City Public Schools, 1960-1986

ERIC Educational Resources Information Center

D'Amico, Diana

2016-01-01

In 1968, New York City's unionized teachers participated in three separate strikes that spanned two school years. Teachers clashed with Black parents and activists who called for community control as both groups sought authority and recognition in the schools. Racialized assumptions in place before and extending beyond the labor skirmish infused…

A Clash of Ideologies: The Reagan Administration Versus the Women's Educational Equity Act.

ERIC Educational Resources Information Center

Cusick, Theresa

The decade of the 1980's has seen the beginning of a great debate over the federal government's involvement in the nation's schools. The history of one program, the Women's Educational Equity Act (WEEA), sheds light on how the Reagan Administration has entered that debate. Congress created WEEA to help schools and colleges educate females for full…

Relations among Ethnic Identity, Parenting Style, and Adolescent Psychosocial Outcomes in European American and East Indian Immigrants.

ERIC Educational Resources Information Center

Bhadha, Bakhtawar

The challenges of identity formation are particularly difficult for minority youth because of the clash of traditional culture and the host culture. This study examined the effects of parenting style, acculturation, and parent and adolescent ethnic identity on the self-esteem and school performance of East Indian and European American adolescents.…

Assessing Bullying: A Guide for Out-of-School Time Program Practitioners. Research-to-Results Brief. Publication #2009-42

ERIC Educational Resources Information Center

Sidorowicz, Kathleen; Hair, Elizabeth C.; Milot, Alyssa

2009-01-01

Conflict among peers is common, and not necessarily a bad thing. Disagreement, teasing, and conflict are part of growing up, and children and adolescents need to develop skills to resolve these clashes. However, bullying, an extreme form of peer conflict or teasing, can be physically and psychologically harmful. Therefore, it is important for…

A Clash of Symbols: An Analysis of Competing Images and Arguments in the AIDS Controversy.

ERIC Educational Resources Information Center

Gilder, Eric

Efforts to contain the spread of Acquired Immune Deficiency Syndrome (AIDS) have been slowed by numerous arguing factions, political, religious, and medical, all of which perceive the AIDS epidemic through a different set of symbols. The images can be more easily understood using Kenneth Boulding's Threat, Integry, and Exchange (or TIE) model. The…

Western Science and Local Thai Wisdom: Using Museum Toys to Develop Bi-Gnosis

ERIC Educational Resources Information Center

Kanhadilok, Peeranut; Watts, Mike

2013-01-01

This article focuses on some of the intersections of two worldviews: Western modern science and a Buddhism-based way of life in Thailand. It enters the debate on the place and practice of Indigenous forms of knowledge and the clashes with formal science education curricula. Our goal is "balanced bi-gnosis": the possession of, and…

From Alaska: A 21st Century Story of Indigenous Self-Determination in Urban American Public Education

ERIC Educational Resources Information Center

Weinstein, Gail L. Israel

2014-01-01

For Alaskan Indigenous people, an acute clash of cultures occurs daily in U.S. public school education. The dynamics used to implement and improve the well-being and graduation outcomes for Alaska Native youth in urban public school are presented. A partnership between Cook Inlet Tribal Council, Inc., an Alaska Native social service nonprofit, and…

Safety and Equality at Odds: OSHA and Title VII Clash over Health Hazards in the Workplace.

ERIC Educational Resources Information Center

Crowell, Donald R.; Copus, David A.

1978-01-01

Discusses the legal problems presented by job health hazards which have a different effect on men and women. Where methods of eliminating or minimizing exposure, as required by the Occupational Safety and Health Act, affect only one sex, the provisions of Title VII of the Civil Rights Act may be violated. (MF)

Interrupting a Legacy of Hatred: Friches Théâtre Urbain's "Lieu Commun"

ERIC Educational Resources Information Center

Haedicke, Susan C.

2016-01-01

In a violent clash between rival gangs from Asnières and Gennevilliers in the banlieue north of Paris, a 15-year-old boy was killed at the metro station Les Courtilles, the last stop on Line 13. Inevitably, revenge attacks occurred. Security was heightened with hundreds of police patrolling the area, but residents and city officials alike…

A Comparison between the Purpose and Goals of Human Resource Development and Adult Education: Whose Interests Are Being Served?

ERIC Educational Resources Information Center

Batchelder, John Stuart; Byxbe, Ferris

2002-01-01

The purposes and goals of adult education and human resource development (HRD) differ and even clash. They find common ground in the personal development function but differ in the control and motivation for learning. Adult education seeks to enable learner self-determination; HRD's focus is enabling organizational control through employee…

Multinational Corporations and British Labour: A Review of Attitudes and Responses.

ERIC Educational Resources Information Center

Gennard, John

Multinational corporations operating in Great Britain, specifically American industry, are arousing fears on the part of British labor, which can be grouped into these categories: (1) a threat to the job security of union members, (2) a change in the balance of power at the collective bargaining table in favor of the employers, (3) a clash of…

The Clash of Two World Views--A Constructivist Analysis of Home Educating Families' Perceptions of Education

ERIC Educational Resources Information Center

Neuman, Ari; Guterman, Oz

2016-01-01

Home education is a phenomenon in which children of varying ages are educated at home rather than in a formal school environment. This phenomenon is becoming increasingly widespread throughout the western world. Research in this field is divided between studying pedagogic aspects and holistic aspects of home education. A group of 30 home educating…

Culture Clash: Mentoring Student Literacy Educators in a Marketised and Instrumentalist Further Education Policyscape

ERIC Educational Resources Information Center

Garbett, Georgina; Orrock, Deborah; Smith, Rob

2013-01-01

At the centre of the study on which this article is based, there is a sense of cultural collision. While from a global perspective, Literacy education has an exciting and radical pedigree, the teaching of Literacy in England has been harnessed to an explicitly instrumentalist policy agenda since the introduction of the Adult Literacy Core…

Walking a Policy Tightrope: The Dilemma of Balancing Diversification and Equality in Chinese College Entrance Examination Reform

ERIC Educational Resources Information Center

You, Zhuran; Hu, Yingzi

2013-01-01

The past decade or so has witnessed a large-scale reform of the Chinese national college entrance exam (the gaokao) system, which nonetheless has been trapped within a dilemma of balancing diversification and equality. Specifically speaking, the reform needs to reconcile the clash between adopting diverse and holistic college admissions to fix the…

Learning to Be a Good Parent across Cultural and Generational Boundaries

ERIC Educational Resources Information Center

Lee, Chi-Ming

2011-01-01

This article focuses on first-person perspectives of a parent-child relationship. The personal experiences of my son and I epitomise the clash of Eastern and Western, traditional and modern cultures in the social context of Taiwan. As a professor of moral education, I reflect on my son's upbringing in order to try to understand and reconcile…

Teaching Eskimo Culture to Eskimo Students: A Special Program for Secondary Schools in Bristol Bay.

ERIC Educational Resources Information Center

Holthaus, Gary H.

Eskimo youth in Bristol Bay, Alaska, caught between the clash of native and white cultures, have difficulty identifying with either culture. The curriculum in Indian schools in the area, geared primarily to white middle-class standards, is not relevant to the students, Textbooks and standardized tests, based on experiences common to a white…

The Tangled World of Teacher Debt: Clashing Rules and Uncertain Benefits for Federal Student-Loan Subsidies

ERIC Educational Resources Information Center

Delisle, Jason; Holt, Alexander

2017-01-01

The world of student loans and debt forgiveness for teachers is a patchwork of overlapping programs, contradictory regulations, and expensive subsidies that date back to Dwight D. Eisenhower's signing of the National Defense Education Act of 1958. The 60-year experiment in using federal loan dollars to encourage students to become teachers could…

Human Nature and the Development of Character: The Clash of Descriptive and Normative Elements in John Stuart Mill's Educational Theory.

ERIC Educational Resources Information Center

Miller, Peter J.; Kim, Ki Su

1988-01-01

Discusses John Stuart Mill's belief in the development of character as a solution to social problems and a worthy educational ideal. Concludes that Mill's belief in education's power to perfect human nature through character development could not be realized within the framework of his anthropological views of human kind. (DMM)

West Europe Report, No. 2204

DTIC Science & Technology

1983-09-15

Markka 38 FRANCE CNPF, Government Clash Over Business Expense Figures "(Alain Barbanel; L’USINE NOUVELLE, 14 Jul 83) 39 ICELAND... FRANCE Leftwing Militants Oppose Economic, Foreign Policies (LE MONDE, 24 Jun 83) 72 NETHERLANDS Developments, Plans of Peace...either domestic or international) from taking place in such countries as France , England, Italy, Belgium and the FRG. In Portugal’s case there are two

When Paradigms Clash: Comments on Cameron and Pierce's Claim That Rewards Do Not Undermine Intrinsic Motivation.

ERIC Educational Resources Information Center

Ryan, Richard M.; Deci, Edward L.

1996-01-01

The conclusion of J. Cameron and W. D. Pierce that rewards do not pose a threat to intrinsic motivation (1994) is a misrepresentation of the literature based on a flawed meta-analysis. Their analysis is more an attempt to defend behaviorist turf rather than meaningful consideration of relevant data and issues. (Author/SLD)

Generations at School: Building an Age-Friendly Workplace

ERIC Educational Resources Information Center

Lovely, Suzette

2010-01-01

In schools around the country, Gen Xers, Millennials, Baby Boomers, and even a Veteran or two are working side by side. While anyone holding a job in this shaky economy is grateful, gratitude does not make generational clashes less difficult. Adding to the mix, many Baby Boomers initially poised for a mass exodus by 2010 are holding on for dear…

Teachers, Students, and Ideological Bias in the College Classroom. Wicked Problems Forum: Freedom of Speech at Colleges and Universities

ERIC Educational Resources Information Center

Mazer, Joseph P.

2018-01-01

Discussions surrounding ideology and free speech on college and university campuses continually occur in the popular press. In this forum, Herbeck (see EJ1171161) chronicles several heated clashes over free speech that have recently erupted on campuses across the country, fueling news stories reported through traditional and social media. Issues…

A Superannuated Physicist's Attempts to Master Music Theory: Resolving Cognitive Conflicts and a Paradigm Clash

ERIC Educational Resources Information Center

Page-Shipp, Roy; van Niekerk, Caroline

2014-01-01

A sexagenarian retired physicist (the first author) set out, with the assistance of members of a university music department, to acquire some insight into Western music theory. For a lifelong singer and seasoned autodidact, this appeared to be a not too formidable challenge, yet he experienced significant difficulty in penetrating the music theory…

A Mythopoetic Methodology: Storytelling as an Act of Scholarship

ERIC Educational Resources Information Center

Shann, Steve

2015-01-01

A pre-service teacher clashes with his mentor and the practicum ends badly. There is distress and a sense of failure all round. Questions get asked. Was the pre-service teacher simply unsuited to this demanding profession? Was the teacher education inadequate? Was the mentor a good fit? Were there the right kinds of support in place? Was the…

M32 analogs? A population of massive ultra-compact dwarf and compact elliptical galaxies in intermediate-redshift clusters

DOE PAGES

Zhang, Yuanyuan; Bell, Eric F.

2017-01-13

Here, we report the discovery of relatively massive, M32-like ultra compact dwarf (UCD) and compact elliptical (CE) galaxy candidates inmore » $$0.2\\lt z\\lt 0.6$$ massive galaxy clusters imaged by the Cluster Lensing And Supernova survey with Hubble (CLASH) survey. Examining the nearly unresolved objects in the survey, we identify a sample of compact objects concentrated around the cluster central galaxies with colors similar to cluster red sequence galaxies. Their colors and magnitudes suggest stellar masses around $${10}^{9}{M}_{\\odot }$$. More than half of these galaxies have half-light radii smaller than 200 pc, falling into the category of massive UCDs and CEs, with properties similar to M32. The properties are consistent with a tidal stripping origin, but we cannot rule out the possibility that they are early-formed compact objects trapped in massive dark matter halos. The 17 CLASH clusters studied in this work on average contain 2.7 of these objects in their central 0.3 Mpc and 0.6 in their central 50 kpc. Our study demonstrates the possibility of statistically characterizing UCDs/CEs with a large set of uniform imaging survey data.« less

Unruly grandmothers, ghosts and ancestors: Chinese elders and the importance of culture in dementia evaluations.

PubMed

Elliott, Kathryn S; Di Minno, Mariann

2006-01-01

This article explores the cultural clashes that occurred when Chinese patients at an Alzheimer's center in California were evaluated for dementia. Lack of familiarity with Chinese culture made the culturally mainstream American clinicians at this center more likely to misinterpret the behavior of elderly Chinese-speaking patients and their families and, thereby, more likely to misdiagnose such patients and suggest culturally inappropriate recommendations. This tendency was reduced when relevant cultural knowledge was incorporated into the clinical evaluation. The evaluation process at this clinic and two patient examples are discussed to illustrate that familiarity with a patient's cultural background is essential for accurate diagnosis and referral. This ethnographic case study places the evaluation process in one particular clinic in cultural context and is suggestive in the way that exploratory qualitative research is meant to be, rather than broadly representative of dementia clinics or clinicians as a whole. However, problems created by cultural clashes at this clinic do suggest that what may be happening at other dementia clinics as they encounter increasingly more patients from diverse cultural backgrounds is an important empirical question worthy of further research, using both qualitative and quantitative methods.

When cultures clash: a case study of the Texaco takeover of Getty Oil and the impact of acculturation on the acquired firm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Altendorf, D.M.

1986-01-01

Historical surveys of merger and acquisition performance indicate that corporate combinations often do not result in the sought after financial success. An ethnographic case study of the Texaco takeover of Getty Oil was undertaken. Based on the in-depth open-ended interviews, field notes, historical accounts, corporate documents, and organizational symbols, data were analyzed using qualitative techniques explicated by Geertz and Glaser and Strauss. The analysis explored cross cultural contact, employee interpretations resulting in related behavioral and performance outcomes, and the factors influencing the type of acculturation observed. Theoretical properties emerged from descriptive accounts. An integrated theory was developed suggesting that themore » form of acculturation that occurs in the combination of two or more firms is a direct consequence of culture differences and the interpretations that the employees make of these differences. Different occurrences - events, strategies, and activities - contributed to corporate culture clash and organizational change. Results also indicated that how meaning is created and managed affects cross cultural contact, employee assessments, and acculturation. Related propositions were generated and implications for future research discussed.« less

M32 analogs? A population of massive ultra-compact dwarf and compact elliptical galaxies in intermediate-redshift clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yuanyuan; Bell, Eric F.

Here, we report the discovery of relatively massive, M32-like ultra compact dwarf (UCD) and compact elliptical (CE) galaxy candidates inmore » $$0.2\\lt z\\lt 0.6$$ massive galaxy clusters imaged by the Cluster Lensing And Supernova survey with Hubble (CLASH) survey. Examining the nearly unresolved objects in the survey, we identify a sample of compact objects concentrated around the cluster central galaxies with colors similar to cluster red sequence galaxies. Their colors and magnitudes suggest stellar masses around $${10}^{9}{M}_{\\odot }$$. More than half of these galaxies have half-light radii smaller than 200 pc, falling into the category of massive UCDs and CEs, with properties similar to M32. The properties are consistent with a tidal stripping origin, but we cannot rule out the possibility that they are early-formed compact objects trapped in massive dark matter halos. The 17 CLASH clusters studied in this work on average contain 2.7 of these objects in their central 0.3 Mpc and 0.6 in their central 50 kpc. Our study demonstrates the possibility of statistically characterizing UCDs/CEs with a large set of uniform imaging survey data.« less

Water-Based Suspensions of Iron Oxide Nanoparticles with Electrostatic or Steric Stabilization by Chitosan: Fabrication, Characterization and Biocompatibility

PubMed Central

Litvinova, Larisa S.; Safronov, Alexander P.; Schupletsova, Valeria V.; Tyukova, Irina S.; Khaziakhmatova, Olga G.; Slepchenko, Galina B.; Yurova, Kristina A.; Cherempey, Elena G.; Kulesh, Nikita A.; Andrade, Ricardo; Beketov, Igor V.; Khlusov, Igor A.

2017-01-01

Present day biomedical applications, including magnetic biosensing, demand better understanding of the interactions between living systems and magnetic nanoparticles (MNPs). In this work spherical MNPs of maghemite were obtained by a highly productive laser target evaporation technique. XRD analysis confirmed the inverse spinel structure of the MNPs (space group Fd-3m). The ensemble obeyed a lognormal size distribution with the median value 26.8 nm and dispersion 0.362. Stabilized water-based suspensions were fabricated using electrostatic or steric stabilization by the natural polymer chitosan. The encapsulation of the MNPs by chitosan makes them resistant to the unfavorable factors for colloidal stability typically present in physiological conditions such as pH and high ionic force. Controlled amounts of suspensions were used for in vitro experiments with human blood mononuclear leukocytes (HBMLs) in order to study their morphofunctional response. For sake of comparison the results obtained in the present study were analyzed together with our previous results of the study of similar suspensions with human mesenchymal stem cells. Suspensions with and without chitosan enhanced the secretion of cytokines by a 24-h culture of HBMLs compared to a control without MNPs. At a dose of 2.3, the MTD of chitosan promotes the stimulating effect of MNPs on cells. In the dose range of MNPs 10–1000 MTD, chitosan “inhibits” cellular secretory activity compared to MNPs without chitosan. Both suspensions did not caused cell death by necrosis, hence, the secretion of cytokines is due to the enhancement of the functional activity of HBMLs. Increased accumulation of MNP with chitosan in the cell fraction at 100 MTD for 24 h exposure, may be due to fixation of chitosan on the outer membrane of HBMLs. The discussed results can be used for an addressed design of cell delivery/removal incorporating multiple activities because of cell capability to avoid phagocytosis by immune cells. They are also promising for the field of biosensor development for the detection of magnetic labels. PMID:29137198

Fluorescence correlation spectroscopy as a sensitive and useful tool for revealing potential overlaps between the epitopes of monoclonal antibodies on viral particles.

PubMed

Richert, Ludovic; Humbert, Nicolas; Larquet, Eric; Girerd-Chambaz, Yves; Manin, Catherine; Ronzon, Frédéric; Mély, Yves

2016-10-01

Although the enzyme-linked immunosorbent assay (ELISA) is well established for quantitating epitopes on inactivated virions used as vaccines, it is less suited for detecting potential overlaps between the epitopes recognized by different antibodies raised against the virions. We used fluorescent correlation spectroscopy (FCS) to detect the potential overlaps between 3 monoclonal antibodies (mAbs 4B7-1H8-2E10, 1E3-3G4, 4H8-3A12-2D3) selected for their ability to specifically recognize poliovirus type 3. Competition of the Alexa488-labeled mAbs with non-labeled mAbs revealed that mAbs 4B7-1H8-2E10 and 4H8-3A12-2D3 compete strongly for their binding sites on the virions, suggesting an important overlap of their epitopes. This was confirmed by the cryo-electron microscopy (cryo EM) structure of the poliovirus type 3 complexed with the corresponding antigen-binding fragments (Fabs) of the mAbs, which revealed that Fabs 4B7-1H8-2E10 and 4H8-3A12-2D3 epitopes share common amino acids. In contrast, a less efficient competition between mAb 1E3-3G4 and mAb 4H8-3A12-2D3 was observed by FCS, and there was no competition between mAbs 1E3-3G4 and 4B7-1H8-2E10. The Fab 1E3-3G4 epitope was found by cryoEM to be close to but distinct from the epitopes of both Fabs 4H8-3A12-2D3 and 4B7-1H8-2E10. Therefore, the FCS data additionally suggest that mAbs 4H8-3A12-2D3 and 4B7-1H8-2E10 bind in a different orientation to their epitopes, so that only the former sterically clashes with the mAb 1E3-3G4 bound to its epitope. Our results demonstrate that FCS can be a highly sensitive and useful tool for assessing the potential overlap of mAbs on viral particles.

Electrochemical aptasensor based on the dual-amplification of G-quadruplex horseradish peroxidase-mimicking DNAzyme and blocking reagent-horseradish peroxidase.

PubMed

Yuan, Yali; Gou, Xuxu; Yuan, Ruo; Chai, Yaqin; Zhuo, Ying; Mao, Li; Gan, Xianxue

2011-06-15

A simple electrochemical aptasensor for sensitive detection of thrombin was fabricated with G-quadruplex horseradish peroxidase-mimicking DNAzyme (hemin/G-quadruplex system) and blocking reagent-horseradish peroxidase as dual signal-amplification scheme. Gold nanoparticles (nano-Au) were firstly electrodeposited onto single wall nanotube (SWNT)-graphene modified electrode surface for the immobilization of electrochemical probe of nickel hexacyanoferrates nanoparticles (NiHCFNPs). Subsequently, another nano-Au layer was electrodeposited for further immobilization of thrombin aptamer (TBA), which later formed hemin/G-quadruplex system with hemin. Horseradish peroxidases (HRP) then served as blocking reagent to block possible remaining active sites and avoided the non-specific adsorption. In the presence of thrombin, the TBA binded to thrombin and the hemin released from the hemin/G-quadruplex electrocatalytic structure, increasing steric hindrance of the aptasensor and decomposing hemin/G-quadruplex electrocatalytic structure, which finally decreased the electrocatalytic efficiency of aptasensor toward H(2)O(2) in the presence of NiHCFNPs with a decreased electrochemical signal. On the basis of the synergistic amplifying action, a detection limit as low as 2 pM for thrombin was obtained. Copyright © 2011 Elsevier B.V. All rights reserved.

Yemen: Background and U.S. Relations

DTIC Science & Technology

2012-11-01

states frequently clashed, and the United States assisted the YAR, with Saudi Arabian financial support, by periodically providing it with weaponry. By...intervene, may have provided President Saleh and his rivals financial incentives to settle their differences and move to a cease-fire. Yemen’s Tenuous...7 Yemeni leaders have long claimed that Iran was trying to destabilize Yemen in order to secure more financial and

JPRS Report, China.

DTIC Science & Technology

1993-04-28

greatly diminished, but regional clashes situation in development occurring in Asia, and read- and elements for insecurity have increased. Regional...because of the three way division of the world. The seven western failure to eradicate internal causes . nations heads-of-state conference, the controversy...security. At the same time, the degree of cause a major upheaval of the world economy. The militarization of international society remains very high; overall

Cultural Clash and Educational Diversity: Immigrant Teachers' Efforts To Rescue the Education of Immigrant Children in Israel.

ERIC Educational Resources Information Center

Epstein, Alek D.; Kheimets, Nina G.

2000-01-01

Presents the results of a study on the Mofet system (Israel), founded by immigrant teachers in 1991 as an effort to educate Russian immigrant children. Argues that although the success of the system is linked to the general education system's failure to meet immigrants' needs, it does not express Russian immigrant's desire for socio-cultural…

Terrorism: National Security Policy and the Home Front.

DTIC Science & Technology

1995-05-15

militia commanders, linked by a common ideology and background. In addition, clans and families have dominated large factions within Hizbollah. In the ... placed significant weight on developing a strong military arm. The State Department’s 1993 report on international terrorism lists Hizbollah’s...with Syria and Lebanon. The most violent round of clashes since the Israeli invasion of Lebanon took place in July 1993, after Hizbollah attacks

Mapping Visual Negotiations in Innovation Driven Teams: A Peek into the Design Process Culture of Graduate Engineering Students

ERIC Educational Resources Information Center

Miranda Mendoza, Constanza Sofia

2013-01-01

Today, the boundaries of disciplines are in a state of flux. The borders are blurred and innovations occur due to the joining of different disciplinary tribes and interaction of teams with diverse epistemological backgrounds. It is not news that this increased diversity in using the design process can bring friction and clashes due to disparate…

"Don't Sell Me the Enemy's Literature": A Self-Study of Teaching Literature in Politically Fraught Contexts

ERIC Educational Resources Information Center

Poyas, Yael

2016-01-01

This article describes a self-study pursuant to a clash between a lecturer and a student concerning the teaching of literature in a politically fraught context. The learning group is composed of Arab and Jewish teachers at a college in northern Israel. The work read by the group expresses a Palestinian perspective. The incident, discussed with…

A Clash of Bottom-Up and Top-Down Processes in Visual Search: The Reversed Letter Effect Revisited

ERIC Educational Resources Information Center

Zhaoping, Li; Frith, Uta

2011-01-01

It is harder to find the letter "N" among its mirror reversals than vice versa, an inconvenient finding for bottom-up saliency accounts based on primary visual cortex (V1) mechanisms. However, in line with this account, we found that in dense search arrays, gaze first landed on either target equally fast. Remarkably, after first landing,…

Tailored Fitness: Culture Clash in the Quest for Combat-Fit Airmen

DTIC Science & Technology

2014-06-01

and conditioning; tobacco cessation, prevention and deglamorization; drug and alcohol abuse awareness and prevention ; general nutrition for all...ages; injury and disease risk education; and stress management and prevention .”6 AFI 36-2905 highlights three other documents that work in...Illustration taken from Center for Disease Control and Prevention Young Adult Obesity Rates Web Site: http://climatecycle.com/newsite/wp- content

Professors Who Blog: Web 2.0 Publishing Venues Don't Need to Clash with Higher Education's Traditional Practices

ERIC Educational Resources Information Center

McLeod, Scott

2007-01-01

Although an increasing number of K-12 educators have taken up blogging in the past few years, blogging professors are still a rarity. Time pressures, entrenched beliefs about peer-reviewed publication, and a lack of familiarity all contribute to the paucity of faculty who regularly blog for public audiences. In this article, several prominent…

A Clash of Native Space and Institutional Place in a Local Choctaw-Upper Creek Memory Site: Decolonizing Critiques and Scholar-Activist Interventions

ERIC Educational Resources Information Center

Black, Jason Edward

2012-01-01

This essay--a combination of authorial narrative and scholarly critique--examines a grassroots organization's (Friends of Historic Northport) campaign to preserve a site in west Alabama where a pivotal Choctaw-Upper Creek battle took place in 1785. The organization has faced opposition from city planners and business leaders intent on developing…

CLASH-VLT: CONSTRAINTS ON THE DARK MATTER EQUATION OF STATE FROM ACCURATE MEASUREMENTS OF GALAXY CLUSTER MASS PROFILES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sartoris, Barbara; Borgani, Stefano; Girardi, Marisa

2014-03-01

A pressureless scenario for the dark matter (DM) fluid is a widely adopted hypothesis, despite the absence of direct observational evidence. According to general relativity, the total mass-energy content of a system shapes the gravitational potential well, but different test particles perceive this potential in different ways depending on their properties. Cluster galaxy velocities, being <

Conflict with China: Prospects, Consequences, and Strategies for Deterrence

DTIC Science & Technology

2011-01-01

Burma / Myanmar . Above and beyond the dangers posed by a clash between the world’s two most populous countries, the presence of nuclear weapons on...Reconnaissance CBRNE Chemical, Biological, Radiological, Nuclear , High-Yield Explosives DMZ Demilitarized Zone DPRK Democratic People’s Republic of Korea EEZ...most concern to the United States. 2 Conflict with China: Prospects, Consequences, and Strategies for Deterrence Occasions for Conflict North Korea

Labor's New Deal for Journalism--The Newspaper Guild in the 1930s

ERIC Educational Resources Information Center

Scott, Dale Benjamin

2009-01-01

The Depression and the New Deal brought together a variety of conditions and social forces that set up a formative clash over the institution of professional journalism. At the heart of that fight was the rise of the American Newspaper Guild and its battle for control over the trusteeship of the freedom of the press. The experience in the news…

Index of International Publications in Aerospace Medicine

DTIC Science & Technology

2010-10-01

to Medical Human Factors. Ottawa, Canada: Canada Communication Group, 1993. Jones DR, Marsh RW. Flight Surgeon Support to United States Air Force...Washington, DC, USA: Government Printing Office, 1996. Coombs CI. Survival in the Sky. New York, NY, USA: William Morrow and Co., 1956. Cushing S. Fatal...Words: Communication Clashes and Aircraft Crashes. Chicago, IL, USA: University of Chicago Press, 1997. Daniel and Florence Guggenheim Aviation

Index of International Publications in Aerospace Medicine

DTIC Science & Technology

2014-05-01

Health and Welfare Canada. The Pilot’s Guide to Medical Human Factors. Ottawa, Canada: Canada Communication Group, 1993. International Commission on...Press, 2003. Condon-Rall ME. Disaster on Green Ramp: The Army’s Response. Washington, DC, USA: Government Printing Office, 1996. Coombs CI. Survival...in the Sky. New York, NY, USA: William Morrow and Co., 1956. Cushing S. Fatal Words: Communication Clashes and Aircraft Crashes. Chicago, IL, USA

Closure of U.S. Military Bases in the Philippines: Impact and Implications

DTIC Science & Technology

1993-04-15

deterrence strategy. The Asia-Pacific Reqion The Asia-Pacific region, also called Western Pacific or East Asia, is a conflict-ridden, culturally diverse...economically dynamic, security sensitive region which has historically spawned a competitive arena for the major powers and their allies and the clash...Korea (North and South), China (Mainland and Taiwan), Hongkong , Vietnam, Laos, Kampuchea, the Philippines, Thailand, Malaysia, Indonesia, Brunei

El Salvador: A Communist Objective.

DTIC Science & Technology

1986-03-31

in planning their military operations. o The series of contacts between Salvadoran communist leaders and officials of serveral communist states that...about 10 inches, monthly, usually limited to afternoon showers. However, in * June and September temporales , or heavy rains, bring a persistent...Jose Mario Lemus alienated most of its popular support in a series of clashes with demonstrating university students, and on October 26, 1960, it was

Between Freedom of the Media and Intrusions of Censorship in German Popular Culture.

ERIC Educational Resources Information Center

Seim, Roland

This paper gives an overview of censorship in Germany. The paper recognizes that between the human right and constitutional law of freedom of speech, art, and press on the one side and the social life of man which must be ensured on the other side, the right of free expression can clash with human dignity. It discusses which books, films, records,…

Socio-Pedagogical Challenges Facing Orphaned and Vulnerable Children in the Aftermath of the 2007-2008 Election Violence in Nakuru County, Kenya

ERIC Educational Resources Information Center

Majanga, Eunice; Mukonyi, Phillip; Vundi, Silvia

2015-01-01

The conflict situations that have afflicted parts of Kenya every five years, in the wake of general elections, since 1992 were most prominent after the disputed presidential elections of 2007. The magnitude of the clashes, loss of life, destruction of property and internal displacement of people were hitherto unwitnessed. The situation of Orphans…

Social, Cultural and Linguistic Factors Affecting the Teaching of Physical Education in the Inner City.

ERIC Educational Resources Information Center

Leibowitz, Harold

The work of the inner city student differs markedly from that of the middle class teacher, resulting in communication problems between teachers and students. The major problem appears to be the clash of cultures that is sustained by the dissimilar value system of the two groups. For instance, the cultural environment of most inner city students is…

When the Goals of Therapists and Patients Clash: A Study of Pedophiles in Treatment

ERIC Educational Resources Information Center

Drapeau, Martin; Korner, Annett C.; Brunet, Louis

2004-01-01

This article first reports the main results and conclusions from a study on 24 pedophile sex abusers in treatment in a Canadian specialized institution. The aims of this study were to better understand what motivates abusers to enter treatment as well as how they experience the treatment on a daily basis and consider it to be helpful. In…

A census of star-forming galaxies in the z ∼ 9-10 universe based on HST+Spitzer observations over 19 clash clusters: three candidate z ∼ 9-10 galaxies and improved constraints on the star formation rate density at z ∼ 9.2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bouwens, R. J.; Franx, M.; Smit, R.

2014-11-10

We utilize a two-color Lyman-break selection criterion to search for z ∼ 9-10 galaxies over the first 19 clusters in the CLASH program. A systematic search yields three z ∼ 9-10 candidates. While we have already reported the most robust of these candidates, MACS1149-JD, two additional z ∼ 9 candidates are also found and have H {sub 160}-band magnitudes of ∼26.2-26.9. A careful assessment of various sources of contamination suggests ≲1 contaminants for our z ∼ 9-10 selection. To determine the implications of these search results for the luminosity function (LF) and star formation rate density at z ∼ 9,more » we introduce a new differential approach to deriving these quantities in lensing fields. Our procedure is to derive the evolution by comparing the number of z ∼ 9-10 galaxy candidates found in CLASH with the number of galaxies in a slightly lower-redshift sample (after correcting for the differences in selection volumes), here taken to be z ∼ 8. This procedure takes advantage of the fact that the relative volumes available for the z ∼ 8 and z ∼ 9-10 selections behind lensing clusters are not greatly dependent on the details of the lensing models. We find that the normalization of the UV LF at z ∼ 9 is just 0.28{sub −0.20}{sup +0.39}× that at z ∼ 8, which is ∼1.4{sub −0.8}{sup +3.0}× lower than extrapolating z ∼ 4-8 LF results. While consistent with the evolution in the UV LF seen at z ∼ 4-8, these results marginally favor a more rapid evolution at z > 8. Compared to similar evolutionary findings from the HUDF, our result is less insensitive to large-scale structure uncertainties, given our many independent sightlines on the high-redshift universe.« less

CLASH: THREE STRONGLY LENSED IMAGES OF A CANDIDATE z Almost-Equal-To 11 GALAXY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coe, Dan; Postman, Marc; Bradley, Larry

2013-01-01

We present a candidate for the most distant galaxy known to date with a photometric redshift of z = 10.7{sup +0.6} {sub -0.4} (95% confidence limits; with z < 9.5 galaxies of known types ruled out at 7.2{sigma}). This J-dropout Lyman break galaxy, named MACS0647-JD, was discovered as part of the Cluster Lensing and Supernova survey with Hubble (CLASH). We observe three magnified images of this galaxy due to strong gravitational lensing by the galaxy cluster MACSJ0647.7+7015 at z = 0.591. The images are magnified by factors of {approx}80, 7, and 2, with the brighter two observed at {approx}26th magnitudemore » AB ({approx}0.15 {mu}Jy) in the WFC3/IR F160W filter ({approx}1.4-1.7 {mu}m) where they are detected at {approx}>12{sigma}. All three images are also confidently detected at {approx}>6{sigma} in F140W ({approx}1.2-1.6 {mu}m), dropping out of detection from 15 lower wavelength Hubble Space Telescope filters ({approx}0.2-1.4 {mu}m), and lacking bright detections in Spitzer/IRAC 3.6 {mu}m and 4.5 {mu}m imaging ({approx}3.2-5.0 {mu}m). We rule out a broad range of possible lower redshift interlopers, including some previously published as high-redshift candidates. Our high-redshift conclusion is more conservative than if we had neglected a Bayesian photometric redshift prior. Given CLASH observations of 17 high-mass clusters to date, our discoveries of MACS0647-JD at z {approx} 10.8 and MACS1149-JD at z {approx} 9.6 are consistent with a lensed luminosity function extrapolated from lower redshifts. This would suggest that low-luminosity galaxies could have reionized the universe. However, given the significant uncertainties based on only two galaxies, we cannot yet rule out the sharp drop-off in number counts at z {approx}> 10 suggested by field searches.« less

CLUMP-3D: Three-dimensional Shape and Structure of 20 CLASH Galaxy Clusters from Combined Weak and Strong Lensing

NASA Astrophysics Data System (ADS)

Chiu, I.-Non; Umetsu, Keiichi; Sereno, Mauro; Ettori, Stefano; Meneghetti, Massimo; Merten, Julian; Sayers, Jack; Zitrin, Adi

2018-06-01

We perform a three-dimensional triaxial analysis of 16 X-ray regular and 4 high-magnification galaxy clusters selected from the CLASH survey by combining two-dimensional weak-lensing and central strong-lensing constraints. In a Bayesian framework, we constrain the intrinsic structure and geometry of each individual cluster assuming a triaxial Navarro–Frenk–White halo with arbitrary orientations, characterized by the mass {M}200{{c}}, halo concentration {c}200{{c}}, and triaxial axis ratios ({q}{{a}}≤slant {q}{{b}}), and investigate scaling relations between these halo structural parameters. From triaxial modeling of the X-ray-selected subsample, we find that the halo concentration decreases with increasing cluster mass, with a mean concentration of {c}200{{c}}=4.82+/- 0.30 at the pivot mass {M}200{{c}}={10}15{M}ȯ {h}-1. This is consistent with the result from spherical modeling, {c}200{{c}}=4.51+/- 0.14. Independently of the priors, the minor-to-major axis ratio {q}{{a}} of our full sample exhibits a clear deviation from the spherical configuration ({q}{{a}}=0.52+/- 0.04 at {10}15{M}ȯ {h}-1 with uniform priors), with a weak dependence on the cluster mass. Combining all 20 clusters, we obtain a joint ensemble constraint on the minor-to-major axis ratio of {q}{{a}}={0.652}-0.078+0.162 and a lower bound on the intermediate-to-major axis ratio of {q}{{b}}> 0.63 at the 2σ level from an analysis with uniform priors. Assuming priors on the axis ratios derived from numerical simulations, we constrain the degree of triaxiality for the full sample to be { \\mathcal T }=0.79+/- 0.03 at {10}15{M}ȯ {h}-1, indicating a preference for a prolate geometry of cluster halos. We find no statistical evidence for an orientation bias ({f}geo}=0.93+/- 0.07), which is insensitive to the priors and in agreement with the theoretical expectation for the CLASH clusters.

CLASH-VLT: constraints on f (R) gravity models with galaxy clusters using lensing and kinematic analyses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pizzuti, L.; Sartoris, B.; Borgani, S.

We perform a maximum likelihood kinematic analysis of the two dynamically relaxed galaxy clusters MACS J1206.2-0847 at z =0.44 and RXC J2248.7-4431 at z =0.35 to determine the total mass profile in modified gravity models, using a modified version of the MAMPOSSt code of Mamon, Biviano and Bou and apos;e. Our work is based on the kinematic and lensing mass profiles derived using the data from the Cluster Lensing And Supernova survey with Hubble (hereafter CLASH) and the spectroscopic follow-up with the Very Large Telescope (hereafter CLASH-VLT). We assume a spherical Navarro-Frenk-White (NFW hereafter) profile in order to obtain amore » constraint on the fifth force interaction range λ for models in which the dependence of this parameter on the environment is negligible at the scale considered (i.e. λ= const ) and fixing the fifth force strength to the value predicted in f (R) gravity. We then use information from lensing analysis to put a prior on the other NFW free parameters. In the case of MACSJ 1206 the joint kinematic+lensing analysis leads to an upper limit on the effective interaction range λ≤1.61 mpc at Δχ{sup 2}=2.71 on the marginalized distribution. For RXJ 2248 instead a possible tension with the ΛCDM model appears when adding lensing information, with a lower limit λ≥0.14 mpc at Δχ{sup 2}=2.71. This is consequence of the slight difference between the lensing and kinematic data, appearing in GR for this cluster, that could in principle be explained in terms of modifications of gravity. We discuss the impact of systematics and the limits of our analysis as well as future improvements of the results obtained. This work has interesting implications in view of upcoming and future large imaging and spectroscopic surveys, that will deliver lensing and kinematic mass reconstruction for a large number of galaxy clusters.« less

Regioselective palladium-catalyzed ring-opening reactions of C1-substituted oxabicyclo[2,2,1]hepta-2,5-diene-2,3-dicarboxylates

PubMed Central

Edmunds, Michael; Raheem, Mohammed Abdul; Boutin, Rebecca; Tait, Katrina

2016-01-01

Summary Palladium-catalyzed ring-opening reactions of C1 substituted 7-oxanorbornadiene derivatives with aryl iodides were investigated. The optimal conditions for this reaction were found to be PdCl2(PPh3)2, ZnCl2, Et3N and Zn in THF. Both steric and electronic factors played a role in the outcome of the reaction as increasing the steric bulk on the bridgehead carbon decreased the yield. These reactions were found to be highly regioselective, giving only one of the two possible regioisomers in all cases. A diverse collection of novel, highly substituted biphenyl derivatives were obtained. PMID:26977182