Tree species exhibit complex patterns of distribution in bottomland hardwood forests

Treesearch

Luben D Dimov; Jim L Chambers; Brian R. Lockhart

2013-01-01

& Context Understanding tree interactions requires an insight into their spatial distribution. & Aims We looked for presence and extent of tree intraspecific spatial point pattern (random, aggregated, or overdispersed) and interspecific spatial point pattern (independent, aggregated, or segregated). & Methods We established twelve 0.64-ha plots in natural...

Managing Physical Education Lessons: An Interactional Approach

ERIC Educational Resources Information Center

Barker, Dean; Annerstedt, Claes

2016-01-01

Physical education (PE) lessons involve complex and dynamic interactive sequences between students, equipment and teacher. The potential for unexpected and/or unintended events is relatively large, a point reflected in an increasing amount of scholarship dealing with classroom management (CM). This scholarship further suggests that unexpected and…

A combined database related and de novo MS-identification of yeast mannose-1-phosphate guanyltransferase PSA1 interaction partners at different phases of batch cultivation

NASA Astrophysics Data System (ADS)

Parviainen, Ville; Joenväärä, Sakari; Peltoniemi, Hannu; Mattila, Pirkko; Renkonen, Risto

2009-04-01

Mass spectrometry-based proteomic research has become one of the main methods in protein-protein interaction research. Several high throughput studies have established an interaction landscape of exponentially growing Baker's yeast culture. However, many of the protein-protein interactions are likely to change in different environmental conditions. In order to examine the dynamic nature of the protein interactions we isolated the protein complexes of mannose-1-phosphate guanyltransferase PSA1 from Saccharomyces cerevisiae at four different time points during batch cultivation. We used the tandem affinity purification (TAP)-method to purify the complexes and subjected the tryptic peptides to LC-MS/MS. The resulting peak lists were analyzed with two different methods: the database related protein identification program X!Tandem and the de novo sequencing program Lutefisk. We observed significant changes in the interactome of PSA1 during the batch cultivation and identified altogether 74 proteins interacting with PSA1 of which only six were found to interact during all time points. All the other proteins showed a more dynamic nature of binding activity. In this study we also demonstrate the benefit of using both database related and de novo methods in the protein interaction research to enhance both the quality and the quantity of observations.

Investigating the Impact of Asp181 Point Mutations on Interactions between PTP1B and Phosphotyrosine Substrate

NASA Astrophysics Data System (ADS)

Liu, Mengyuan; Wang, Lushan; Sun, Xun; Zhao, Xian

2014-05-01

Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin and leptin signaling, which suggests that it is an attractive therapeutic target in type II diabetes and obesity. The aim of this research is to explore residues which interact with phosphotyrosine substrate can be affected by D181 point mutations and lead to increased substrate binding. To achieve this goal, molecular dynamics simulations were performed on wild type (WT) and two mutated PTP1B/substrate complexes. The cross-correlation and principal component analyses show that point mutations can affect the motions of some residues in the active site of PTP1B. Moreover, the hydrogen bond and energy decomposition analyses indicate that apart from residue 181, point mutations have influence on the interactions of substrate with several residues in the active site of PTP1B.

Introductory Remarks: Points of Concern with Current Interpretations of the Effects of Early Malnutrition on Mental Development

ERIC Educational Resources Information Center

Barnes, R. H.

1972-01-01

Emphasizes that from a practical point of view, it is important that studies with malnourished children emphasize the interactions between nutrition and environment rather than attempt complex, costly experiments which hopefully will assess the contribution of each of the components alone. (Author/JM)

The genetic landscape of a physical interaction

PubMed Central

Diss, Guillaume

2018-01-01

A key question in human genetics and evolutionary biology is how mutations in different genes combine to alter phenotypes. Efforts to systematically map genetic interactions have mostly made use of gene deletions. However, most genetic variation consists of point mutations of diverse and difficult to predict effects. Here, by developing a new sequencing-based protein interaction assay – deepPCA – we quantified the effects of >120,000 pairs of point mutations on the formation of the AP-1 transcription factor complex between the products of the FOS and JUN proto-oncogenes. Genetic interactions are abundant both in cis (within one protein) and trans (between the two molecules) and consist of two classes – interactions driven by thermodynamics that can be predicted using a three-parameter global model, and structural interactions between proximally located residues. These results reveal how physical interactions generate quantitatively predictable genetic interactions. PMID:29638215

Can the Isolated-Elements Strategy Be Improved by Targeting Points of High Cognitive Load for Additional Practice?

ERIC Educational Resources Information Center

Ayres, Paul

2013-01-01

Reducing problem complexity by isolating elements has been shown to be an effective instructional strategy. Novices, in particular, benefit from learning from worked examples that contain partially interacting elements rather than worked examples that provide full interacting elements. This study investigated whether the isolating-elements…

Studies of Point Defects and Defect Interactions in Metals Using Perturbed Gamma Gamma Angular Correlations

NASA Astrophysics Data System (ADS)

Shropshire, Steven Leslie

Point defects in plastically deformed Au, Pt, and Ni were studied with atomic-scale sensitivity using the perturbed gamma-gamma angular correlations (PAC) technique by monitoring formation and transformation of complexes of vacancy defects with very dilute ^{111}In/ ^{111}Cd solute probes. Three topics were investigated: (1) Production of vacancy defects during plastic deformation of Au was investigated to differentiate models of defect production. Concentrations of mono-, di-, and tri-vacancy species were measured in Au, and the ratio of mono- to di-vacancies was found to be independent of the amount of deformation. Results indicate that point defects are produced in correlated lattice locations, such as in "strings", as a consequence of dislocation interactions and not at random locations. (2) Hydrogen interactions with vacancy-solute complexes were studied in Pt. From thermal detrapping experiments, binding of hydrogen in complexes with mono-, di- and tri-vacancies was determined using a model for hydrogen diffusing in a medium with traps, with enthalpies all measured in the narrow range 0.23-0.28 eV, proving that the binding is insensitive to the precise structure of small vacancy clusters. Nuclear relaxation of the probe in a trivacancy complex in Pt was studied as a function of temperature, from which an activation energy of 0.34 eV was measured. This value is inconsistent with relaxation caused by diffusion or trapping of hydrogen, but explainable by dynamical hopping of the PAC probe atom in a cage of vacancies. (3) By observing transformations between vacancy-solute complexes induced by annihilation reactions, it was demonstrated that interstitials are produced during plastic deformation. The evolution of concentrations of the different vacancy complexes under an interstitial flux was measured and analyzed using a kinetic-rate model, from which interstitial capture cross-sections for the different vacancy complexes and the relative quantities of interstitial species in the flux were determined. Deformation of Au was found to produce only mono- and di-interstitial fluxes in a 1:2 ratio. Cross-sections increased rapidly with the number of vacancies, which is attributed to the amount of relaxation of lattice strains around solute-vacancy complexes.

Anomalous polymer collapse winding angle distributions

NASA Astrophysics Data System (ADS)

Narros, A.; Owczarek, A. L.; Prellberg, T.

2018-03-01

In two dimensions polymer collapse has been shown to be complex with multiple low temperature states and multi-critical points. Recently, strong numerical evidence has been provided for a long-standing prediction of universal scaling of winding angle distributions, where simulations of interacting self-avoiding walks show that the winding angle distribution for N-step walks is compatible with the theoretical prediction of a Gaussian with a variance growing asymptotically as Clog N . Here we extend this work by considering interacting self-avoiding trails which are believed to be a model representative of some of the more complex behaviour. We provide robust evidence that, while the high temperature swollen state of this model has a winding angle distribution that is also Gaussian, this breaks down at the polymer collapse point and at low temperatures. Moreover, we provide some evidence that the distributions are well modelled by stretched/compressed exponentials, in contradistinction to the behaviour found in interacting self-avoiding walks. Dedicated to Professor Stu Whittington on the occasion of his 75th birthday.

Linear σ-hole⋯CO⋯σ-hole intermolecular interactions between carbon monoxide and dihalogen molecules XY (X, Y=Cl, Br).

PubMed

Yang, Xing; Yang, Fan; Wu, Rui-Zhi; Yan, Chao-Xian; Zhou, Da-Gang; Zhou, Pan-Pan; Yao, Xiaojun

2017-09-01

Carbon monoxide can interact with two dihalogen molecules XY (X, Y=Cl, Br) in the form of X(Y)⋯COX(Y)⋯CO⋯X(Y)X(Y) trimeric complex, and their nature and characteristics were investigated at MP2/aug-cc-pVDZ level without and with counterpoise method, together with single point calculations at CCSD(T)/aug-cc-pVDZ level. The optimized geometries, stretching modes and interaction energies of a series of X(Y)⋯COX(Y)⋯CO⋯X(Y)X(Y) trimeric complexes were obtained and discussed. The cooperativity in these complexes was evaluated. EDA analyses reveal that the electrostatic interaction is the dominant net driving force in each trimer, but the contributions of other interactions like exchange, dispersion and polarization interactions are also important. QTAIM and NCI analyses confirm the existence of attractive halogen-bonding interactions. Additionally, EDDMF analysis was employed for the component dimers of these trimers, which indicates that the formation of halogen-bonding interactions is closely related to the charge shift and the rearrangement of electronic density in the formation of these complexes. The results would provide valuable insight into for these linear halogen bonds. Copyright © 2017 Elsevier Inc. All rights reserved.

An experimental and theoretical study on the interaction of DNA and BSA with novel Ni2 +, Cu2 + and VO2 + complexes derived from vanillin bidentate Schiff base ligand

NASA Astrophysics Data System (ADS)

Dostani, Morteza; Kianfar, Ali Hossein; Mahmood, Wan Ahmad Kamil; Dinari, Mohammad; Farrokhpour, Hossein; Sabzalian, Mohammad R.; Abyar, Fatemeh; Azarian, Mohammad Hossein

2017-06-01

In this investigation, the structure of bidentate N,N-Schiff base ligand of vanillin, (E)-4-(((2-amino-5-nitrophenyl)imino)methyl)-2-methoxyphenol (HL) was determined by single crystal X-ray diffraction. The interaction of new [CuL2], [NiL2] and [VOL2] complexes with DNA and BSA was explored through UV-Vis and fluorescence spectroscopy. The electronic spectra changes displayed an isosbestic point for the complexes upon titration with DNA. The Kb values for the complexes [CuL2], [NiL2] and [VOL2] were 2.4 × 105, 1.9 × 105 and 4.2 × 104, respectively. [CuL2] complex was bound more toughly than [NiL2] and [VOL2] complexes. These complexes had a significant interaction with Bovine Serum Albumin (BSA) and the results demonstrated that the quenching mechanism was a static procedure. Also, the complexes interacted with BSA by more than one binding site (n > 1). Finally, the theoretical studies were performed using the docking method to calculate the binding constants and recognize the binding site of the DNA and BSA with the complexes. The ligand and complexes including Ni2 +, Cu2 + and VO2 + ions were colonized by fungal growth.

A Method for Predicting Protein Complexes from Dynamic Weighted Protein-Protein Interaction Networks.

PubMed

Liu, Lizhen; Sun, Xiaowu; Song, Wei; Du, Chao

2018-06-01

Predicting protein complexes from protein-protein interaction (PPI) network is of great significance to recognize the structure and function of cells. A protein may interact with different proteins under different time or conditions. Existing approaches only utilize static PPI network data that may lose much temporal biological information. First, this article proposed a novel method that combines gene expression data at different time points with traditional static PPI network to construct different dynamic subnetworks. Second, to further filter out the data noise, the semantic similarity based on gene ontology is regarded as the network weight together with the principal component analysis, which is introduced to deal with the weight computing by three traditional methods. Third, after building a dynamic PPI network, a predicting protein complexes algorithm based on "core-attachment" structural feature is applied to detect complexes from each dynamic subnetworks. Finally, it is revealed from the experimental results that our method proposed in this article performs well on detecting protein complexes from dynamic weighted PPI networks.

Collective Genetic Interaction Effects and the Role of Antigen Presenting Cells in Autoimmune Diseases

DTIC Science & Technology

2017-01-12

RESEARCH ARTICLE Collective Genetic Interaction Effects and the Role of Antigen-Presenting Cells in Autoimmune Diseases Hyung Jun Woo*, Chenggang Yu...autoimmunity. Genetic predispositions center around the major histocompatibility complex (MHC) class II loci involved in antigen presentation, the key...helper and regulatory T cells showing strong dis- ease-associated interactions with B cells. Our results provide direct genetic evidence point- ing to

A Unique Computational Algorithm to Simulate Probabilistic Multi-Factor Interaction Model Complex Material Point Behavior

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Abumeri, Galib H.

2010-01-01

The Multi-Factor Interaction Model (MFIM) is used to evaluate the divot weight (foam weight ejected) from the launch external tanks. The multi-factor has sufficient degrees of freedom to evaluate a large number of factors that may contribute to the divot ejection. It also accommodates all interactions by its product form. Each factor has an exponent that satisfies only two points--the initial and final points. The exponent describes a monotonic path from the initial condition to the final. The exponent values are selected so that the described path makes sense in the absence of experimental data. In the present investigation, the data used was obtained by testing simulated specimens in launching conditions. Results show that the MFIM is an effective method of describing the divot weight ejected under the conditions investigated.

Point interactions, metamaterials, and PT-symmetry

NASA Astrophysics Data System (ADS)

Mostafazadeh, Ali

2016-05-01

We express the boundary conditions for TE and TM waves at the interfaces of an infinite planar slab of homogeneous metamaterial as certain point interactions and use them to compute the transfer matrix of the system. This allows us to demonstrate the omnidirectional reflectionlessness of Veselago's slab for waves of arbitrary wavelength, reveal the translational and reflection symmetry of this slab, explore the laser threshold condition and coherent perfect absorption for active negative-index metamaterials, introduce a point interaction modeling phase-conjugation, determine the corresponding antilinear transfer matrix, and offer a simple proof of the equivalence of Veselago's slab with a pair of parallel phase-conjugating plates. We also study the connection between certain optical setups involving metamaterials and a class of PT-symmetric quantum systems defined on wedge-shape contours in the complex plane. This provides a physical interpretation for the latter.

Bark beetles (Scolytidae, Coleoptera) in Slovenia with special regard to species in burnt pine forests

Treesearch

Maja Jurc

2003-01-01

Ecological conditions in Slovenia are very complex and heterogeneous due to the influence and interaction among the various climatic, tectonic, edaphic, orographic, lithologic - transitional (ecotonic) regions. Slovenia is a meeting-point of the Alps, the Mediterranean, the Dinaric Mountain Region and the Pannonian Lowland. This complexity of ecological factors has...

Bifurcation of avoided crossing at an exceptional point in the dispersion of sound and light in locally resonant media

NASA Astrophysics Data System (ADS)

Maznev, A. A.

2018-03-01

The avoided crossing behavior in the interaction of propagating sound or light waves with resonant inclusions is analyzed using a simple model of an acoustic medium containing damped mass-spring oscillators, which is shown to be equivalent to the Lorentz oscillator model in the elementary dispersion theory in optics. Two classes of experimental situations dictating the choice in the analysis of the dispersion relation are identified. If the wavevector is regarded as the independent variable and frequency as a complex function of the wavevector, then the avoided crossing bifurcates at an exceptional point at a certain value of the parameter γβ-1/2 , where γ and β characterize the oscillator damping and interaction strength, respectively. This behavior is not observed if the wavevector is regarded as a complex function of frequency.

Instantaneous Transfer Entropy for the Study of Cardiovascular and Cardiorespiratory Nonstationary Dynamics.

PubMed

Valenza, Gaetano; Faes, Luca; Citi, Luca; Orini, Michele; Barbieri, Riccardo

2018-05-01

Measures of transfer entropy (TE) quantify the direction and strength of coupling between two complex systems. Standard approaches assume stationarity of the observations, and therefore are unable to track time-varying changes in nonlinear information transfer with high temporal resolution. In this study, we aim to define and validate novel instantaneous measures of TE to provide an improved assessment of complex nonstationary cardiorespiratory interactions. We here propose a novel instantaneous point-process TE (ipTE) and validate its assessment as applied to cardiovascular and cardiorespiratory dynamics. In particular, heartbeat and respiratory dynamics are characterized through discrete time series, and modeled with probability density functions predicting the time of the next physiological event as a function of the past history. Likewise, nonstationary interactions between heartbeat and blood pressure dynamics are characterized as well. Furthermore, we propose a new measure of information transfer, the instantaneous point-process information transfer (ipInfTr), which is directly derived from point-process-based definitions of the Kolmogorov-Smirnov distance. Analysis on synthetic data, as well as on experimental data gathered from healthy subjects undergoing postural changes confirms that ipTE, as well as ipInfTr measures are able to dynamically track changes in physiological systems coupling. This novel approach opens new avenues in the study of hidden, transient, nonstationary physiological states involving multivariate autonomic dynamics in cardiovascular health and disease. The proposed method can also be tailored for the study of complex multisystem physiology (e.g., brain-heart or, more in general, brain-body interactions).

General and craniofacial development are complex adaptive processes influenced by diversity.

PubMed

Brook, A H; O'Donnell, M Brook; Hone, A; Hart, E; Hughes, T E; Smith, R N; Townsend, G C

2014-06-01

Complex systems are present in such diverse areas as social systems, economies, ecosystems and biology and, therefore, are highly relevant to dental research, education and practice. A Complex Adaptive System in biological development is a dynamic process in which, from interacting components at a lower level, higher level phenomena and structures emerge. Diversity makes substantial contributions to the performance of complex adaptive systems. It enhances the robustness of the process, allowing multiple responses to external stimuli as well as internal changes. From diversity comes variation in outcome and the possibility of major change; outliers in the distribution enhance the tipping points. The development of the dentition is a valuable, accessible model with extensive and reliable databases for investigating the role of complex adaptive systems in craniofacial and general development. The general characteristics of such systems are seen during tooth development: self-organization; bottom-up emergence; multitasking; self-adaptation; variation; tipping points; critical phases; and robustness. Dental findings are compatible with the Random Network Model, the Threshold Model and also with the Scale Free Network Model which has a Power Law distribution. In addition, dental development shows the characteristics of Modularity and Clustering to form Hierarchical Networks. The interactions between the genes (nodes) demonstrate Small World phenomena, Subgraph Motifs and Gene Regulatory Networks. Genetic mechanisms are involved in the creation and evolution of variation during development. The genetic factors interact with epigenetic and environmental factors at the molecular level and form complex networks within the cells. From these interactions emerge the higher level tissues, tooth germs and mineralized teeth. Approaching development in this way allows investigation of why there can be variations in phenotypes from identical genotypes; the phenotype is the outcome of perturbations in the cellular systems and networks, as well as of the genotype. Understanding and applying complexity theory will bring about substantial advances not only in dental research and education but also in the organization and delivery of oral health care. © 2014 Australian Dental Association.

A spectroscopic study on the interaction between gold nanoparticles and hemoglobin

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

Garabagiu, Sorina, E-mail: sgarabagiu@itim-cj.ro

2011-12-15

Highlights: Black-Right-Pointing-Pointer The interaction was studied using UV-vis and fluorescence spectroscopy. Black-Right-Pointing-Pointer Gold nanoparticles quench the fluorescence emission of hemoglobin solution. Black-Right-Pointing-Pointer The binding and thermodynamic constants were calculated. Black-Right-Pointing-Pointer Major impact: electrochemical applications of the complex onto a substrate. -- Abstract: The interaction between horse hemoglobin and gold nanoparticles was studied using optical spectroscopy. UV-vis and fluorescence spectra show that a spontaneous binding process occurred between hemoglobin and gold nanoparticles. The Soret band of hemoglobin in the presence of gold nanoparticles does not show significant changes, which proves that the protein retained its biological function. A shift to longermore » wavelengths appears in the plasmonic band of gold nanoparticles upon the attachment of hemoglobin molecules. Gold nanoparticles quench the fluorescence emission of tryptophan residues in the structure of hemoglobin. The Stern-Volmer quenching constant, the binding constant and the number of binding sites were also calculated. Thermodynamic parameters indicate that the binding was mainly due to hydrophobic interactions.« less

Molecular interaction of the first 3 enzymes of the de novo pyrimidine biosynthetic pathway of Trypanosoma cruzi

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

Nara, Takeshi, E-mail: tnara@juntendo.ac.jp; Hashimoto, Muneaki; Hirawake, Hiroko

2012-02-03

Highlights: Black-Right-Pointing-Pointer An Escherichia coli strain co-expressing CPSII, ATC, and DHO of Trypanosoma cruzi was constructed. Black-Right-Pointing-Pointer Molecular interactions between CPSII, ATC, and DHO of T. cruzi were demonstrated. Black-Right-Pointing-Pointer CPSII bound with both ATC and DHO. Black-Right-Pointing-Pointer ATC bound with both CPSII and DHO. Black-Right-Pointing-Pointer A functional tri-enzyme complex might precede the establishment of the fused enzyme. -- Abstract: The first 3 reaction steps of the de novo pyrimidine biosynthetic pathway are catalyzed by carbamoyl-phosphate synthetase II (CPSII), aspartate transcarbamoylase (ATC), and dihydroorotase (DHO), respectively. In eukaryotes, these enzymes are structurally classified into 2 types: (1) a CPSII-DHO-ATC fusionmore » enzyme (CAD) found in animals, fungi, and amoebozoa, and (2) stand-alone enzymes found in plants and the protist groups. In the present study, we demonstrate direct intermolecular interactions between CPSII, ATC, and DHO of the parasitic protist Trypanosoma cruzi, which is the causative agent of Chagas disease. The 3 enzymes were expressed in a bacterial expression system and their interactions were examined. Immunoprecipitation using an antibody specific for each enzyme coupled with Western blotting-based detection using antibodies for the counterpart enzymes showed co-precipitation of all 3 enzymes. From an evolutionary viewpoint, the formation of a functional tri-enzyme complex may have preceded-and led to-gene fusion to produce the CAD protein. This is the first report to demonstrate the structural basis of these 3 enzymes as a model of CAD. Moreover, in conjunction with the essentiality of de novo pyrimidine biosynthesis in the parasite, our findings provide a rationale for new strategies for developing drugs for Chagas disease, which target the intermolecular interactions of these 3 enzymes.« less

Specific non-monotonous interactions increase persistence of ecological networks.

PubMed

Yan, Chuan; Zhang, Zhibin

2014-03-22

The relationship between stability and biodiversity has long been debated in ecology due to opposing empirical observations and theoretical predictions. Species interaction strength is often assumed to be monotonically related to population density, but the effects on stability of ecological networks of non-monotonous interactions that change signs have not been investigated previously. We demonstrate that for four kinds of non-monotonous interactions, shifting signs to negative or neutral interactions at high population density increases persistence (a measure of stability) of ecological networks, while for the other two kinds of non-monotonous interactions shifting signs to positive interactions at high population density decreases persistence of networks. Our results reveal a novel mechanism of network stabilization caused by specific non-monotonous interaction types through either increasing stable equilibrium points or reducing unstable equilibrium points (or both). These specific non-monotonous interactions may be important in maintaining stable and complex ecological networks, as well as other networks such as genes, neurons, the internet and human societies.

Super-complexes of adhesion GPCRs and neural guidance receptors

NASA Astrophysics Data System (ADS)

Jackson, Verity A.; Mehmood, Shahid; Chavent, Matthieu; Roversi, Pietro; Carrasquero, Maria; Del Toro, Daniel; Seyit-Bremer, Goenuel; Ranaivoson, Fanomezana M.; Comoletti, Davide; Sansom, Mark S. P.; Robinson, Carol V.; Klein, Rüdiger; Seiradake, Elena

2016-04-01

Latrophilin adhesion-GPCRs (Lphn1-3 or ADGRL1-3) and Unc5 cell guidance receptors (Unc5A-D) interact with FLRT proteins (FLRT1-3), thereby promoting cell adhesion and repulsion, respectively. How the three proteins interact and function simultaneously is poorly understood. We show that Unc5D interacts with FLRT2 in cis, controlling cell adhesion in response to externally presented Lphn3. The ectodomains of the three proteins bind cooperatively. Crystal structures of the ternary complex formed by the extracellular domains reveal that Lphn3 dimerizes when bound to FLRT2:Unc5, resulting in a stoichiometry of 1:1:2 (FLRT2:Unc5D:Lphn3). This 1:1:2 complex further dimerizes to form a larger `super-complex' (2:2:4), using a previously undescribed binding motif in the Unc5D TSP1 domain. Molecular dynamics simulations, point-directed mutagenesis and mass spectrometry demonstrate the stability and molecular properties of these complexes. Our data exemplify how receptors increase their functional repertoire by forming different context-dependent higher-order complexes.

The effects of syntactic complexity on the human-computer interaction

NASA Technical Reports Server (NTRS)

Chechile, R. A.; Fleischman, R. N.; Sadoski, D. M.

1986-01-01

Three divided-attention experiments were performed to evaluate the effectiveness of a syntactic analysis of the primary task of editing flight route-way-point information. For all editing conditions, a formal syntactic expression was developed for the operator's interaction with the computer. In terms of the syntactic expression, four measures of syntactic were examined. Increased syntactic complexity did increase the time to train operators, but once the operators were trained, syntactic complexity did not influence the divided-attention performance. However, the number of memory retrievals required of the operator significantly accounted for the variation in the accuracy, workload, and task completion time found on the different editing tasks under attention-sharing conditions.

Free-Surface Fluid-Object Interaction for the Large-Scale Computation of Ship Hydrodynamics Phenomena

DTIC Science & Technology

2014-05-21

simulating air-water free -surface flow, fluid-object interaction (FOI), and fluid-structure interaction (FSI) phenomena for complex geometries, and...with no limitations on the motion of the free surface, and with particular emphasis on ship hydrodynamics. The following specific research objectives...were identified for this project: 1) Development of a theoretical framework for free -surface flow, FOI and FSI that is a suitable starting point

Computational Methods to Predict Protein Interaction Partners

NASA Astrophysics Data System (ADS)

Valencia, Alfonso; Pazos, Florencio

In the new paradigm for studying biological phenomena represented by Systems Biology, cellular components are not considered in isolation but as forming complex networks of relationships. Protein interaction networks are among the first objects studied from this new point of view. Deciphering the interactome (the whole network of interactions for a given proteome) has been shown to be a very complex task. Computational techniques for detecting protein interactions have become standard tools for dealing with this problem, helping and complementing their experimental counterparts. Most of these techniques use genomic or sequence features intuitively related with protein interactions and are based on "first principles" in the sense that they do not involve training with examples. There are also other computational techniques that use other sources of information (i.e. structural information or even experimental data) or are based on training with examples.

Modulating of the pnicogen-bonding by a H⋯π interaction: An ab initio study.

PubMed

Esrafili, Mehdi D; Sadr-Mousavi, Asma

2017-08-01

An ab initio study of the cooperativity in XH 2 P⋯NCH⋯Z and XH 2 P⋯CNH⋯Z complexes (X=F, Cl, Br, CN, NC; Z=C 2 H 2 ,C 6 H 6 ) connected by pnicogen-bonding and H⋯π interactions is carried out by means of MP2 computational method. A detailed analysis of the structures, interaction energies and bonding properties is performed on these systems. For each set of the complexes considered, a favorable cooperativity is observed, especially in X=F and CN complexes. However, for a given X or Z, the amount of cooperativity effects in XH 2 P⋯CNH⋯Z complexes are more important than XH 2 P⋯NCH⋯Z counterparts. Besides, the influence of a H⋯π interaction on a P⋯N (C) bond is more pronounced than that of a P⋯N (C) bond on a H⋯π bond. The quantum theory of atoms in molecules shows that ternary complexes have increased electron densities at their bond critical points relative to the corresponding binary systems. The results also indicate that the strength of the P⋯N(C) and H⋯π interactions increases in the presence of the solvent. Copyright © 2017 Elsevier Inc. All rights reserved.

LiveWire interactive boundary extraction algorithm based on Haar wavelet transform and control point set direction search

NASA Astrophysics Data System (ADS)

Cheng, Jun; Zhang, Jun; Tian, Jinwen

2015-12-01

Based on deep analysis of the LiveWire interactive boundary extraction algorithm, a new algorithm focusing on improving the speed of LiveWire algorithm is proposed in this paper. Firstly, the Haar wavelet transform is carried on the input image, and the boundary is extracted on the low resolution image obtained by the wavelet transform of the input image. Secondly, calculating LiveWire shortest path is based on the control point set direction search by utilizing the spatial relationship between the two control points users provide in real time. Thirdly, the search order of the adjacent points of the starting node is set in advance. An ordinary queue instead of a priority queue is taken as the storage pool of the points when optimizing their shortest path value, thus reducing the complexity of the algorithm from O[n2] to O[n]. Finally, A region iterative backward projection method based on neighborhood pixel polling has been used to convert dual-pixel boundary of the reconstructed image to single-pixel boundary after Haar wavelet inverse transform. The algorithm proposed in this paper combines the advantage of the Haar wavelet transform and the advantage of the optimal path searching method based on control point set direction search. The former has fast speed of image decomposition and reconstruction and is more consistent with the texture features of the image and the latter can reduce the time complexity of the original algorithm. So that the algorithm can improve the speed in interactive boundary extraction as well as reflect the boundary information of the image more comprehensively. All methods mentioned above have a big role in improving the execution efficiency and the robustness of the algorithm.

Using machine learning tools to model complex toxic interactions with limited sampling regimes.

PubMed

Bertin, Matthew J; Moeller, Peter; Guillette, Louis J; Chapman, Robert W

2013-03-19

A major impediment to understanding the impact of environmental stress, including toxins and other pollutants, on organisms, is that organisms are rarely challenged by one or a few stressors in natural systems. Thus, linking laboratory experiments that are limited by practical considerations to a few stressors and a few levels of these stressors to real world conditions is constrained. In addition, while the existence of complex interactions among stressors can be identified by current statistical methods, these methods do not provide a means to construct mathematical models of these interactions. In this paper, we offer a two-step process by which complex interactions of stressors on biological systems can be modeled in an experimental design that is within the limits of practicality. We begin with the notion that environment conditions circumscribe an n-dimensional hyperspace within which biological processes or end points are embedded. We then randomly sample this hyperspace to establish experimental conditions that span the range of the relevant parameters and conduct the experiment(s) based upon these selected conditions. Models of the complex interactions of the parameters are then extracted using machine learning tools, specifically artificial neural networks. This approach can rapidly generate highly accurate models of biological responses to complex interactions among environmentally relevant toxins, identify critical subspaces where nonlinear responses exist, and provide an expedient means of designing traditional experiments to test the impact of complex mixtures on biological responses. Further, this can be accomplished with an astonishingly small sample size.

Tree invasion of a montane meadow complex: temporal trends, spatial patterns, and biotic interactions

Treesearch

Charles B. Halpern; Joseph A. Antos; Janine M. Rice; Ryan D. Haugo; Nicole L. Lang

2010-01-01

We combined spatial point pattern analysis, population age structures, and a time-series of stem maps to quantify spatial and temporal patterns of conifer invasion over a 200-yr period in three plots totaling 4 ha. In combination, spatial and temporal patterns of establishment suggest an invasion process shaped by biotic interactions, with facilitation promoting...

Design and Mechanical Stability Analysis of the Interaction Region for the Inverse Compton Scattering Gamma-Ray Source Using Finite Element Method

NASA Astrophysics Data System (ADS)

Khizhanok, Andrei

Development of a compact source of high-spectral brilliance and high impulse frequency gamma rays has been in scope of Fermi National Accelerator Laboratory for quite some time. Main goal of the project is to develop a setup to support gamma rays detection test and gamma ray spectroscopy. Potential applications include but not limited to nuclear astrophysics, nuclear medicine, oncology ('gamma knife'). Present work covers multiple interconnected stages of development of the interaction region to ensure high levels of structural strength and vibrational resistance. Inverse Compton scattering is a complex phenomenon, in which charged particle transfers a part of its energy to a photon. It requires extreme precision as the interaction point is estimated to be 20 microm. The slightest deflection of the mirrors will reduce effectiveness of conversion by orders of magnitude. For acceptable conversion efficiency laser cavity also must have >1000 finesse value, which requires a trade-off between size, mechanical stability, complexity, and price of the setup. This work focuses on advantages and weak points of different designs of interaction regions as well as in-depth description of analyses performed. This includes laser cavity amplification and finesse estimates, natural frequency mapping, harmonic analysis. Structural analysis is required as interaction must occur under high vacuum conditions.

Dynamic interactions between Pit-1 and C/EBPalpha in the pituitary cell nucleus.

PubMed

Demarco, Ignacio A; Voss, Ty C; Booker, Cynthia F; Day, Richard N

2006-11-01

The homeodomain (HD) transcription factors are a structurally conserved family of proteins that, through networks of interactions with other nuclear proteins, control patterns of gene expression during development. For example, the network interactions of the pituitary-specific HD protein Pit-1 control the development of anterior pituitary cells and regulate the expression of the hormone products in the adult cells. Inactivating mutations in Pit-1 disrupt these processes, giving rise to the syndrome of combined pituitary hormone deficiency. Pit-1 interacts with CCAAT/enhancer-binding protein alpha (C/EBPalpha) to regulate prolactin transcription. Here, we used the combination of biochemical analysis and live-cell microscopy to show that two different point mutations in Pit-1, which disrupted distinct activities, affected the dynamic interactions between Pit-1 and C/EBPalpha in different ways. The results showed that the first alpha-helix of the POU-S domain is critical for the assembly of Pit-1 with C/EBPalpha, and they showed that DNA-binding activity conferred by the HD is critical for the final intranuclear positioning of the metastable complex. This likely reflects more general mechanisms that govern cell-type-specific transcriptional control, and the results from the analysis of the point mutations could indicate an important link between the mislocalization of transcriptional complexes and disease processes.

Cation and anion dependence of stable geometries and stabilization energies of alkali metal cation complexes with FSA(-), FTA(-), and TFSA(-) anions: relationship with physicochemical properties of molten salts.

PubMed

Tsuzuki, Seiji; Kubota, Keigo; Matsumoto, Hajime

2013-12-19

Stable geometries and stabilization energies (Eform) of the alkali metal complexes with bis(fluorosulfonyl)amide, (fluorosulfonyl)(trifluoromethylslufonyl)amide and bis(trifluoromethylsulfonyl)amide (FSA(-), FTA(-) and TFSA(-)) were studied by ab initio molecular orbital calculations. The FSA(-) complexes prefer the bidentate structures in which two oxygen atoms of two SO2 groups have contact with the metal cation. The FTA(-) and TFSA(-) complexes with Li(+) and Na(+) prefer the bidentate structures, while the FTA(-) and TFSA(-) complexes with Cs(+) prefer tridentate structures in which the metal cation has contact with two oxygen atoms of an SO2 group and one oxygen atom of another SO2 group. The two structures are nearly isoenergetic in the FTA(-) and TFSA(-) complexes with K(+) and Rb(+). The magnitude of Eform depends on the alkali metal cation significantly. The Eform calculated for the most stable TFSA(-) complexes with Li(+), Na(+), K(+), Rb(+) and Cs(+) cations at the MP2/6-311G** level are -137.2, -110.5, -101.1, -89.6, and -84.1 kcal/mol, respectively. The viscosity and ionic conductivity of the alkali TFSA molten salts have strong correlation with the magnitude of the attraction. The viscosity increases and the ionic conductivity decreases with the increase of the attraction. The melting points of the alkali TFSA and alkali BETA molten salts also have correlation with the magnitude of the Eform, which strongly suggests that the magnitude of the attraction play important roles in determining the melting points of these molten salts. The anion dependence of the Eform calculated for the complexes is small (less than 2.9 kcal/mol). This shows that the magnitude of the attraction is not the cause of the low melting points of alkali FTA molten salts compared with those of corresponding alkali TFSA molten salts. The electrostatic interactions are the major source of the attraction in the complexes. The electrostatic energies for the most stable TFSA(-) complexes with the five alkali metal cations are -140.3, -119.4, -104.1, -96.9, and -91.1 kcal/mol, respectively. The induction interactions also contribute to the attraction. In particular, the induction interactions are large in the Li(+) complexes. The induction energies for the five complexes are -46.6, -25.2, -17.5, -13.3, and -10.4 kcal/mol, respectively.

High Molecular Weight Forms of Mammalian Respiratory Chain Complex II

PubMed Central

Nůsková, Hana; Holzerová, Eliška; Vrbacký, Marek; Pecina, Petr; Hejzlarová, Kateřina; Kľučková, Katarína; Rohlena, Jakub; Neuzil, Jiri; Houštěk, Josef

2013-01-01

Mitochondrial respiratory chain is organised into supramolecular structures that can be preserved in mild detergent solubilisates and resolved by native electrophoretic systems. Supercomplexes of respiratory complexes I, III and IV as well as multimeric forms of ATP synthase are well established. However, the involvement of complex II, linking respiratory chain with tricarboxylic acid cycle, in mitochondrial supercomplexes is questionable. Here we show that digitonin-solubilised complex II quantitatively forms high molecular weight structures (CIIhmw) that can be resolved by clear native electrophoresis. CIIhmw structures are enzymatically active and differ in electrophoretic mobility between tissues (500 – over 1000 kDa) and cultured cells (400–670 kDa). While their formation is unaffected by isolated defects in other respiratory chain complexes, they are destabilised in mtDNA-depleted, rho0 cells. Molecular interactions responsible for the assembly of CIIhmw are rather weak with the complexes being more stable in tissues than in cultured cells. While electrophoretic studies and immunoprecipitation experiments of CIIhmw do not indicate specific interactions with the respiratory chain complexes I, III or IV or enzymes of the tricarboxylic acid cycle, they point out to a specific interaction between CII and ATP synthase. PMID:23967256

Emotional contagion and proto-organizing in human interaction dynamics

PubMed Central

Hazy, James K.; Boyatzis, Richard E.

2015-01-01

This paper combines the complexity notions of phase transitions and tipping points with recent advances in cognitive neuroscience to propose a general theory of human proto-organizing. It takes as a premise that a necessary prerequisite for organizing, or “proto-organizing,” occurs through emotional contagion in subpopulations of human interaction dynamics in complex ecosystems. Emotional contagion is posited to engender emotional understanding and identification with others, a social process that acts as a mechanism that enables (or precludes) cooperative responses to opportunities and risks. Propositions are offered and further research is suggested. PMID:26124736

Reduced Point Charge Models of Proteins: Effect of Protein-Water Interactions in Molecular Dynamics Simulations of Ubiquitin Systems.

PubMed

Leherte, Laurence; Vercauteren, Daniel P

2017-10-26

We investigate the influence of various solvent models on the structural stability and protein-water interface of three ubiquitin complexes (PDB access codes: 1Q0W , 2MBB , 2G3Q ) modeled using the Amber99sb force field (FF) and two different point charge distributions. A previously developed reduced point charge model (RPCM), wherein each amino acid residue is described by a limited number of point charges, is tested and compared to its all-atom (AA) version. The complexes are solvated in TIP4P-Ew or TIP3P type water molecules, involving either the scaling of the Lennard-Jones protein-O water interaction parameters, or the coarse-grain (CG) SIRAH water description. The best agreements between the RPCM and AA models were obtained for structural, protein-water, and ligand-ubiquitin properties when using the TIP4P-Ew water FF with a scaling factor γ of 0.7. At the RPCM level, a decrease in γ, or the inclusion of SIRAH particles, allows weakening of the protein-water interactions. It results in a slight collapse of the protein structure and a less compact hydration shell and, thus, in a decrease in the number of protein-water and water-water H-bonds. The dynamics of the surface protein atoms and of the water shell molecules are also slightly refrained, which allow the generation of stable RPCM trajectories.

Point-particle method to compute diffusion-limited cellular uptake.

PubMed

Sozza, A; Piazza, F; Cencini, M; De Lillo, F; Boffetta, G

2018-02-01

We present an efficient point-particle approach to simulate reaction-diffusion processes of spherical absorbing particles in the diffusion-limited regime, as simple models of cellular uptake. The exact solution for a single absorber is used to calibrate the method, linking the numerical parameters to the physical particle radius and uptake rate. We study the configurations of multiple absorbers of increasing complexity to examine the performance of the method by comparing our simulations with available exact analytical or numerical results. We demonstrate the potential of the method to resolve the complex diffusive interactions, here quantified by the Sherwood number, measuring the uptake rate in terms of that of isolated absorbers. We implement the method in a pseudospectral solver that can be generalized to include fluid motion and fluid-particle interactions. As a test case of the presence of a flow, we consider the uptake rate by a particle in a linear shear flow. Overall, our method represents a powerful and flexible computational tool that can be employed to investigate many complex situations in biology, chemistry, and related sciences.

A Novel Algorithm for Detecting Protein Complexes with the Breadth First Search

PubMed Central

Tang, Xiwei; Wang, Jianxin; Li, Min; He, Yiming; Pan, Yi

2014-01-01

Most biological processes are carried out by protein complexes. A substantial number of false positives of the protein-protein interaction (PPI) data can compromise the utility of the datasets for complexes reconstruction. In order to reduce the impact of such discrepancies, a number of data integration and affinity scoring schemes have been devised. The methods encode the reliabilities (confidence) of physical interactions between pairs of proteins. The challenge now is to identify novel and meaningful protein complexes from the weighted PPI network. To address this problem, a novel protein complex mining algorithm ClusterBFS (Cluster with Breadth-First Search) is proposed. Based on the weighted density, ClusterBFS detects protein complexes of the weighted network by the breadth first search algorithm, which originates from a given seed protein used as starting-point. The experimental results show that ClusterBFS performs significantly better than the other computational approaches in terms of the identification of protein complexes. PMID:24818139

On the role of electrostatics in protein-protein interactions

NASA Astrophysics Data System (ADS)

Zhang, Zhe; Witham, Shawn; Alexov, Emil

2011-06-01

The role of electrostatics in protein-protein interactions and binding is reviewed in this paper. A brief outline of the computational modeling, in the framework of continuum electrostatics, is presented and the basic electrostatic effects occurring upon the formation of the complex are discussed. The effect of the salt concentration and pH of the water phase on protein-protein binding free energy is demonstrated which indicates that the increase of the salt concentration tends to weaken the binding, an observation that is attributed to the optimization of the charge-charge interactions across the interface. It is pointed out that the pH-optimum (pH of optimal binding affinity) varies among the protein-protein complexes, and perhaps is a result of their adaptation to particular subcellular compartments. The similarities and differences between hetero- and homo-complexes are outlined and discussed with respect to the binding mode and charge complementarity.

On the physical nature of halogen bonds: a QTAIM study.

PubMed

Syzgantseva, Olga A; Tognetti, Vincent; Joubert, Laurent

2013-09-12

In this article, we report a detailed study on halogen bonds in complexes of CHCBr, CHCCl, CH2CHBr, FBr, FCl, and ClBr with a set of Lewis bases (NH3, OH2, SH2, OCH2, OH(-), Br(-)). To obtain insight into the physical nature of these bonds, we extensively used Bader's Quantum Theory of Atoms-in-Molecules (QTAIM). With this aim, in addition to the examination of the bond critical points properties, we apply Pendás' Interacting Quantum Atoms (IQA) scheme, which enables rigorous and physical study of each interaction at work in the formation of the halogen-bonded complexes. In particular, the influence of primary and secondary interactions on the stability of the complexes is analyzed, and the roles of electrostatics and exchange are notably discussed and compared. Finally, relationships between QTAIM descriptors and binding energies are inspected.

On the role of electrostatics on protein-protein interactions

PubMed Central

Zhang, Zhe; Witham, Shawn; Alexov, Emil

2011-01-01

The role of electrostatics on protein-protein interactions and binding is reviewed in this article. A brief outline of the computational modeling, in the framework of continuum electrostatics, is presented and basic electrostatic effects occurring upon the formation of the complex are discussed. The role of the salt concentration and pH of the water phase on protein-protein binding free energy is demonstrated and indicates that the increase of the salt concentration tends to weaken the binding, an observation that is attributed to the optimization of the charge-charge interactions across the interface. It is pointed out that the pH-optimum (pH of optimal binding affinity) varies among the protein-protein complexes, and perhaps is a result of their adaptation to particular subcellular compartment. At the end, the similarities and differences between hetero- and homo-complexes are outlined and discussed with respect to the binding mode and charge complementarity. PMID:21572182

Three-dimensional potential energy surface of selected carbohydrates' CH/π dispersion interactions calculated by high-level quantum mechanical methods.

PubMed

Kozmon, Stanislav; Matuška, Radek; Spiwok, Vojtěch; Koča, Jaroslav

2011-05-09

In this study we present the first systematic computational three-dimensional scan of carbohydrate hydrophobic patches for the ability to interact through CH/π dispersion interactions. The carbohydrates β-d-glucopyranose, β-d-mannopyranose and α-l-fucopyranose were studied in a complex with a benzene molecule, which served as a model of the CH/π interaction in carbohydrate/protein complexes. The 3D relaxed scans were performed at the SCC-DFTB-D level with 3 757 grid points for both carbohydrate hydrophobic sides. The interaction energy of all grid points was recalculated at the DFT-D BP/def2-TZVPP level. The results obtained clearly show highly delimited and separated areas around each CH group, with an interaction energy up to -5.40 kcal mol(-1) . The results also show that with increasing H⋅⋅⋅π distance these delimited areas merge and form one larger region, which covers all hydrogen atoms on that specific carbohydrate side. Simultaneously, the interaction becomes weaker with an energy of -2.5 kcal mol(-1) . All local energy minima were optimized at the DFT-D BP/def2-TZVPP level and the interaction energies of these complexes were refined by use of the high-level ab initio computation at the CCSD(T)/CBS level. Results obtained from the optimization suggest that the CH group hydrogen atoms are not equivalent and the interaction energy at the CCSD(T)/CBS level range from -3.54 to -5.40 kcal mol(-1) . These results also reveal that the optimal H⋅⋅⋅π distance for the CH/π dispersion interaction is approximately (2.310±0.030) Å, and the angle defined as carbon-hydrogen-benzene geometrical centre is (180±30)°. These results reveal that whereas the dispersion interactions with the lowest interaction energies are quite strictly located in space, the slightly higher interaction energy regions adopt a much larger space. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural Dynamics Investigation of Human Family 1 & 2 Cystatin-Cathepsin L1 Interaction: A Comparison of Binding Modes.

PubMed

Nandy, Suman Kumar; Seal, Alpana

2016-01-01

Cystatin superfamily is a large group of evolutionarily related proteins involved in numerous physiological activities through their inhibitory activity towards cysteine proteases. Despite sharing the same cystatin fold, and inhibiting cysteine proteases through the same tripartite edge involving highly conserved N-terminal region, L1 and L2 loop; cystatins differ widely in their inhibitory affinity towards C1 family of cysteine proteases and molecular details of these interactions are still elusive. In this study, inhibitory interactions of human family 1 & 2 cystatins with cathepsin L1 are predicted and their stability and viability are verified through protein docking & comparative molecular dynamics. An overall stabilization effect is observed in all cystatins on complex formation. Complexes are mostly dominated by van der Waals interaction but the relative participation of the conserved regions varied extensively. While van der Waals contacts prevail in L1 and L2 loop, N-terminal segment chiefly acts as electrostatic interaction site. In fact the comparative dynamics study points towards the instrumental role of L1 loop in directing the total interaction profile of the complex either towards electrostatic or van der Waals contacts. The key amino acid residues surfaced via interaction energy, hydrogen bonding and solvent accessible surface area analysis for each cystatin-cathepsin L1 complex influence the mode of binding and thus control the diverse inhibitory affinity of cystatins towards cysteine proteases.

Complexity of generic biochemical circuits: topology versus strength of interactions.

PubMed

Tikhonov, Mikhail; Bialek, William

2016-12-06

The historical focus on network topology as a determinant of biological function is still largely maintained today, illustrated by the rise of structure-only approaches to network analysis. However, biochemical circuits and genetic regulatory networks are defined both by their topology and by a multitude of continuously adjustable parameters, such as the strength of interactions between nodes, also recognized as important. Here we present a class of simple perceptron-based Boolean models within which comparing the relative importance of topology versus interaction strengths becomes a quantitatively well-posed problem. We quantify the intuition that for generic networks, optimization of interaction strengths is a crucial ingredient of achieving high complexity, defined here as the number of fixed points the network can accommodate. We propose a new methodology for characterizing the relative role of parameter optimization for topologies of a given class.

Insight into the Structure of Light Harvesting Complex II and its Stabilization in Detergent Solution

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

Cardoso, Mateus B; Smolensky, Dmitriy; Heller, William T

2009-01-01

The structure of spinach light-harvesting complex II (LHC II), stabilized in a solution of the detergent n-octyl-{beta}-d-glucoside (BOG), was investigated by small-angle neutron scattering (SANS). Physicochemical characterization of the isolated complex indicated that it was pure (>95%) and also in its native trimeric state. SANS with contrast variation was used to investigate the properties of the protein-detergent complex at three different H{sub 2}O/D{sub 2}O contrast match points, enabling the scattering properties of the protein and detergent to be investigated independently. The topological shape of LHC II, determined using ab initio shape restoration methods from the SANS data at the contrastmore » match point of BOG, was consistent with the X-ray crystallographic structure of LHC II (Liu et al. Nature 2004 428, 287-292). The interactions of the protein and detergent were investigated at the contrast match point for the protein and also in 100% D{sub 2}O. The data suggested that BOG micelle structure was altered by its interaction with LHC II, but large aggregate structures were not formed. Indirect Fourier transform analysis of the LHC II/BOG scattering curves showed that the increase in the maximum dimension of the protein-detergent complex was consistent with the presence of a monolayer of detergent surrounding the protein. A model of the LHC II/BOG complex was generated to interpret the measurements made in 100% D{sub 2}O. This model adequately reproduced the overall size of the LHC II/BOG complex, but demonstrated that the detergent does not have a highly regular shape that surrounds the hydrophobic periphery of LHC II. In addition to demonstrating that natively structured LHC II can be produced for functional characterization and for use in artificial solar energy applications, the analysis and modeling approaches described here can be used for characterizing detergent-associated {alpha}-helical transmembrane proteins.« less

Investigation of charge-transfer hydrogen bonding interaction of 1-(2-pyridylazo)-2-naphthol (PAN) and 4-(2-Pyridylazo)resorcinol (PAR) with chloranilic acid through experimental and DFT studies

NASA Astrophysics Data System (ADS)

Karmakar, Animesh; Singh, Bula

2018-07-01

The H-bonding interaction of 1-(2-pyridylazo)-2-naphthol (PAN) and 4-(2-Pyridylazo) resorcinol (PAR) with chloranilic acid (CLA) have been considered spectroscopically in methanol solvent. PAN and PAR were used as a ligand and this two ligands has diverse application in spectrophotometric, chelatometric analysis of different metal ions. However, it is seen as of the literature analysis that no molecular complex of PAN and PAR with CLA was reported. The creation of charge-transfer H-bonded adduct gives a outlook to progress the physico-chemical scenery of the donor. So the complex of PAN and PAR with chloranilic acid was recounted in this work in methanol medium. Both the hydrogen-bonded molecular complexes have been prepared and identified using 1H NMR, FT-IR, and elemental analysis. Spectroscopic data point out that PAN and PAR discretely interact with CLA by a physically potent H-bonding interaction. The thermal constancy of the above molecular complexes has been determined by TGA-DTA analysis. The computational calculation also supported the development of the H-bonded charge-transfer adduct.

Structural and energetic study of cation-π-cation interactions in proteins.

PubMed

Pinheiro, Silvana; Soteras, Ignacio; Gelpí, Josep Lluis; Dehez, François; Chipot, Christophe; Luque, F Javier; Curutchet, Carles

2017-04-12

Cation-π interactions of aromatic rings and positively charged groups are among the most important interactions in structural biology. The role and energetic characteristics of these interactions are well established. However, the occurrence of cation-π-cation interactions is an unexpected motif, which raises intriguing questions about its functional role in proteins. We present a statistical analysis of the occurrence, composition and geometrical preferences of cation-π-cation interactions identified in a set of non-redundant protein structures taken from the Protein Data Bank. Our results demonstrate that this structural motif is observed at a small, albeit non-negligible frequency in proteins, and suggest a preference to establish cation-π-cation motifs with Trp, followed by Tyr and Phe. Furthermore, we have found that cation-π-cation interactions tend to be highly conserved, which supports their structural or functional role. Finally, we have performed an energetic analysis of a representative subset of cation-π-cation complexes combining quantum-chemical and continuum solvation calculations. Our results point out that the protein environment can strongly screen the cation-cation repulsion, leading to an attractive interaction in 64% of the complexes analyzed. Together with the high degree of conservation observed, these results suggest a potential stabilizing role in the protein fold, as demonstrated recently for a miniature protein (Craven et al., J. Am. Chem. Soc. 2016, 138, 1543). From a computational point of view, the significant contribution of non-additive three-body terms challenges the suitability of standard additive force fields for describing cation-π-cation motifs in molecular simulations.

In silico study of the human rhodopsin and meta rhodopsin II/S-arrestin complexes: impact of single point mutations related to retina degenerative diseases.

PubMed

Mokarzel-Falcón, Leonardo; Padrón-García, Juan Alexander; Carrasco-Velar, Ramón; Berry, Colin; Montero-Cabrera, Luis A

2008-03-01

We propose two models of the human S-arrestin/rhodopsin complex in the inactive dark adapted rhodopsin and meta rhodopsin II form, obtained by homology modeling and knowledge based docking. First, a homology model for the human S-arrestin was built and validated by molecular dynamics, showing an average root mean square deviation difference from the pattern behavior of 0.76 A. Then, combining the human S-arrestin model and the modeled structure of the two human rhodopsin forms, we propose two models of interaction for the human S-arrestin/rhodopsin complex. The models involve two S-arrestin regions related to the N domain (residues 68-78; 170-182) and a third constituent of the C domain (248-253), with the rhodopsin C terminus (330-348). Of the 22 single point mutations related to retinitis pigmentosa and congenital night blindness located in the cytoplasmatic portion of rhodopsin or in S-arrestin, our models locate 16 in the interaction region and relate two others to possible dimer formation. Our calculations also predict that the light activated complex is more stable than the dark adapted rhodopsin and, therefore, of higher affinity to S-arrestin. 2008 Wiley-Liss, Inc.

A Spatially-Registered, Massively Parallelised Data Structure for Interacting with Large, Integrated Geodatasets

NASA Astrophysics Data System (ADS)

Irving, D. H.; Rasheed, M.; O'Doherty, N.

2010-12-01

The efficient storage, retrieval and interactive use of subsurface data present great challenges in geodata management. Data volumes are typically massive, complex and poorly indexed with inadequate metadata. Derived geomodels and interpretations are often tightly bound in application-centric and proprietary formats; open standards for long-term stewardship are poorly developed. Consequently current data storage is a combination of: complex Logical Data Models (LDMs) based on file storage formats; 2D GIS tree-based indexing of spatial data; and translations of serialised memory-based storage techniques into disk-based storage. Whilst adequate for working at the mesoscale over a short timeframes, these approaches all possess technical and operational shortcomings: data model complexity; anisotropy of access; scalability to large and complex datasets; and weak implementation and integration of metadata. High performance hardware such as parallelised storage and Relational Database Management System (RDBMS) have long been exploited in many solutions but the underlying data structure must provide commensurate efficiencies to allow multi-user, multi-application and near-realtime data interaction. We present an open Spatially-Registered Data Structure (SRDS) built on Massively Parallel Processing (MPP) database architecture implemented by a ANSI SQL 2008 compliant RDBMS. We propose a LDM comprising a 3D Earth model that is decomposed such that each increasing Level of Detail (LoD) is achieved by recursively halving the bin size until it is less than the error in each spatial dimension for that data point. The value of an attribute at that point is stored as a property of that point and at that LoD. It is key to the numerical efficiency of the SRDS that it is under-pinned by a power-of-two relationship thus precluding the need for computationally intensive floating point arithmetic. Our approach employed a tightly clustered MPP array with small clusters of storage, processors and memory communicating over a high-speed network inter-connect. This is a shared-nothing architecture where resources are managed within each cluster unlike most other RDBMSs. Data are accessed on this architecture by their primary index values which utilises the hashing algorithm for point-to-point access. The hashing algorithm’s main role is the efficient distribution of data across the clusters based on the primary index. In this study we used 3D seismic volumes, 2D seismic profiles and borehole logs to demonstrate application in both (x,y,TWT) and (x,y,z)-space. In the SRDS the primary index is a composite column index of (x,y) to avoid invoking time-consuming full table scans as is the case in tree-based systems. This means that data access is isotropic. A query for data in a specified spatial range permits retrieval recursively by point-to-point queries within each nested LoD yielding true linear performance up to the Petabyte scale with hardware scaling presenting the primary limiting factor. Our architecture and LDM promotes: realtime interaction with massive data volumes; streaming of result sets and server-rendered 2D/3D imagery; rigorous workflow control and auditing; and in-database algorithms run directly against data as a HPC cloud service.

Probabilistic Multi-Factor Interaction Model for Complex Material Behavior

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Abumeri, Galib H.

2008-01-01

The Multi-Factor Interaction Model (MFIM) is used to evaluate the divot weight (foam weight ejected) from the launch external tanks. The multi-factor has sufficient degrees of freedom to evaluate a large number of factors that may contribute to the divot ejection. It also accommodates all interactions by its product form. Each factor has an exponent that satisfies only two points, the initial and final points. The exponent describes a monotonic path from the initial condition to the final. The exponent values are selected so that the described path makes sense in the absence of experimental data. In the present investigation the data used was obtained by testing simulated specimens in launching conditions. Results show that the MFIM is an effective method of describing the divot weight ejected under the conditions investigated.

Probabilistic Multi-Factor Interaction Model for Complex Material Behavior

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Abumeri, Galib H.

2008-01-01

The Multi-Factor Interaction Model (MFIM) is used to evaluate the divot weight (foam weight ejected) from the launch external tanks. The multi-factor has sufficient degrees of freedom to evaluate a large number of factors that may contribute to the divot ejection. It also accommodates all interactions by its product form. Each factor has an exponent that satisfies only two points the initial and final points. The exponent describes a monotonic path from the initial condition to the final. The exponent values are selected so that the described path makes sense in the absence of experimental data. In the present investigation, the data used was obtained by testing simulated specimens in launching conditions. Results show that the MFIM is an effective method of describing the divot weight ejected under the conditions investigated.

Simulation and display of macromolecular complexes

NASA Technical Reports Server (NTRS)

Nir, S.; Garduno, R.; Rein, R.; Macelroy, R. D.

1977-01-01

In association with an investigation of the interaction of proteins with DNA and RNA, an interactive computer program for building, manipulating, and displaying macromolecular complexes has been designed. The system provides perspective, planar, and stereoscopic views on the computer terminal display, as well as views for standard and nonstandard observer locations. The molecule or its parts may be rotated and/or translated in any direction; bond connections may be added or removed by the viewer. Molecular fragments may be juxtaposed in such a way that given bonds are aligned, and given planes and points coincide. Another subroutine provides for the duplication of a given unit such as a DNA or amino-acid base.

Influence of the R823W mutation on the interaction of the ANKS6-ANKS3: insights from molecular dynamics simulation and free energy analysis.

PubMed

Kan, Wei; Fang, Fengqin; Chen, Lin; Wang, Ruige; Deng, Qigang

2016-05-01

The sterile alpha motif (SAM) domain of the protein ANKS6, a protein-protein interaction domain, is responsible for autosomal dominant polycystic kidney disease. Although the disease is the result of the R823W point mutation in the SAM domain of the protein ANKS6, the molecular details are still unclear. We applied molecular dynamics simulations, the principal component analysis, and the molecular mechanics Poisson-Boltzmann surface area binding free energy calculation to explore the structural and dynamic effects of the R823W point mutation on the complex ANKS6-ANKS3 (PDB ID: 4NL9) in comparison to the wild proteins. The energetic analysis presents that the wild type has a more stable structure than the mutant. The R823W point mutation not only disrupts the structure of the ANKS6 SAM domain but also negatively affects the interaction of the ANKS6-ANKS3. These results further clarify the previous experiments to understand the ANKS6-ANKS3 interaction comprehensively. In summary, this study would provide useful suggestions to understand the interaction of these proteins and their fatal action on mediating kidney function.

Metal-ligand bond directionality in the M2-NH3 complexes (M = Cu, Ag and Au)

NASA Astrophysics Data System (ADS)

Eskandari, K.; Ebadinejad, F.

2018-05-01

The metal-ligand bonds in the M2-NH3 complexes (M = Au, Ag and Cu) are directional and the M-M-N angles tend to be linear. Natural energy decomposition analysis (NEDA) and localised molecular orbital energy decomposition analysis (LMOEDA) approaches indicate that the metal-ligand bonds in these complexes are mainly electrostatic in nature, however, the electrostatic is not the cause of the linearity of M-M-N arrangements. Instead, NEDA shows that the charge transfer and core repulsion are mainly responsible for the directionality of these bonds. In the LMOEDA point of view, the repulsion term is the main reason for the linearity of these complexes. Interacting quantum atoms (IQA) analysis shows that inter-atomic and inter-fragment interactions favour the nonlinear arrangements; however, these terms are compensated by the atomic self-energies, which stabilise the linear structure.

Interactive Land-Use Optimization Using Laguerre Voronoi Diagram with Dynamic Generating Point Allocation

NASA Astrophysics Data System (ADS)

Chaidee, S.; Pakawanwong, P.; Suppakitpaisarn, V.; Teerasawat, P.

2017-09-01

In this work, we devise an efficient method for the land-use optimization problem based on Laguerre Voronoi diagram. Previous Voronoi diagram-based methods are more efficient and more suitable for interactive design than discrete optimization-based method, but, in many cases, their outputs do not satisfy area constraints. To cope with the problem, we propose a force-directed graph drawing algorithm, which automatically allocates generating points of Voronoi diagram to appropriate positions. Then, we construct a Laguerre Voronoi diagram based on these generating points, use linear programs to adjust each cell, and reconstruct the diagram based on the adjustment. We adopt the proposed method to the practical case study of Chiang Mai University's allocated land for a mixed-use complex. For this case study, compared to other Voronoi diagram-based method, we decrease the land allocation error by 62.557 %. Although our computation time is larger than the previous Voronoi-diagram-based method, it is still suitable for interactive design.

Impact Detection for Characterization of Complex Multiphase Flows

NASA Astrophysics Data System (ADS)

Chan, Wai Hong Ronald; Urzay, Javier; Mani, Ali; Moin, Parviz

2016-11-01

Multiphase flows often involve a wide range of impact events, such as liquid droplets impinging on a liquid pool or gas bubbles coalescing in a liquid medium. These events contribute to a myriad of large-scale phenomena, including breaking waves on ocean surfaces. As impacts between surfaces necessarily occur at isolated points, numerical simulations of impact events will require the resolution of molecular scales near the impact points for accurate modeling. This can be prohibitively expensive unless subgrid impact and breakup models are formulated to capture the effects of the interactions. The first step in a large-eddy simulation (LES) based computational methodology for complex multiphase flows like air-sea interactions requires effective detection of these impact events. The starting point of this work is a collision detection algorithm for structured grids on a coupled level set / volume of fluid (CLSVOF) solver adapted from an earlier algorithm for cloth animations that triangulates the interface with the marching cubes method. We explore the extension of collision detection to a geometric VOF solver and to unstructured grids. Supported by ONR/A*STAR. Agency of Science, Technology and Research, Singapore; Office of Naval Research, USA.

Structural insights of the MLF1/14-3-3 interaction.

PubMed

Molzan, Manuela; Weyand, Michael; Rose, Rolf; Ottmann, Christian

2012-02-01

Myeloid leukaemia factor 1 (MLF1) binds to 14-3-3 adapter proteins by a sequence surrounding Ser34 with the functional consequences of this interaction largely unknown. We present here the high-resolution crystal structure of this binding motif [MLF1(29-42)pSer34] in complex with 14-3-3ε and analyse the interaction with isothermal titration calorimetry. Fragment-based ligand discovery employing crystals of the binary 14-3-3ε/MLF1(29-42)pSer34 complex was used to identify a molecule that binds to the interface rim of the two proteins, potentially representing the starting point for the development of a small molecule that stabilizes the MLF1/14-3-3 protein-protein interaction. Such a compound might be used as a chemical biology tool to further analyse the 14-3-3/MLF1 interaction without the use of genetic methods. Database Structural data are available in the Protein Data Bank under the accession number(s) 3UAL [14-3-3ε/MLF1(29-42)pSer34 complex] and 3UBW [14-3-3ε/MLF1(29-42)pSer34/3-pyrrolidinol complex] Structured digital abstract •  14-3-3 epsilon and MLF1 bind by x-ray crystallography (View interaction) •  14-3-3 epsilon and MLF1 bind by isothermal titration calorimetry (View Interaction: 1, 2). © 2011 The Authors Journal compilation © 2011 FEBS.

Structural Dynamics Investigation of Human Family 1 & 2 Cystatin-Cathepsin L1 Interaction: A Comparison of Binding Modes

PubMed Central

Nandy, Suman Kumar; Seal, Alpana

2016-01-01

Cystatin superfamily is a large group of evolutionarily related proteins involved in numerous physiological activities through their inhibitory activity towards cysteine proteases. Despite sharing the same cystatin fold, and inhibiting cysteine proteases through the same tripartite edge involving highly conserved N-terminal region, L1 and L2 loop; cystatins differ widely in their inhibitory affinity towards C1 family of cysteine proteases and molecular details of these interactions are still elusive. In this study, inhibitory interactions of human family 1 & 2 cystatins with cathepsin L1 are predicted and their stability and viability are verified through protein docking & comparative molecular dynamics. An overall stabilization effect is observed in all cystatins on complex formation. Complexes are mostly dominated by van der Waals interaction but the relative participation of the conserved regions varied extensively. While van der Waals contacts prevail in L1 and L2 loop, N-terminal segment chiefly acts as electrostatic interaction site. In fact the comparative dynamics study points towards the instrumental role of L1 loop in directing the total interaction profile of the complex either towards electrostatic or van der Waals contacts. The key amino acid residues surfaced via interaction energy, hydrogen bonding and solvent accessible surface area analysis for each cystatin-cathepsin L1 complex influence the mode of binding and thus control the diverse inhibitory affinity of cystatins towards cysteine proteases. PMID:27764212

Tool for simplifying the complex interactions within resilient communities

NASA Astrophysics Data System (ADS)

Stwertka, C.; Albert, M. R.; White, K. D.

2016-12-01

In recent decades, scientists have observed and documented impacts from climate change that will impact multiple sectors, will be impacted by decisions from multiple sectors, and will change over time. This complex human-engineered system has a large number of moving, interacting parts, which are interdependent and evolve over time towards their purpose. Many of the existing resilience frameworks and vulnerability frameworks focus on interactions between the domains, but do not include the structure of the interactions. We present an engineering systems approach to investigate the structural elements that influence a community's ability to be resilient. In this presentation we will present and analyze four common methods for building community resilience, utilizing our common framework. For several existing case studies we examine the stress points in the system and identify the impacts on the outcomes from the case studies. In ongoing research we will apply our system tool to a new case in the field.

A Single-Cell Biochemistry Approach Reveals PAR Complex Dynamics during Cell Polarization.

PubMed

Dickinson, Daniel J; Schwager, Francoise; Pintard, Lionel; Gotta, Monica; Goldstein, Bob

2017-08-21

Regulated protein-protein interactions are critical for cell signaling, differentiation, and development. For the study of dynamic regulation of protein interactions in vivo, there is a need for techniques that can yield time-resolved information and probe multiple protein binding partners simultaneously, using small amounts of starting material. Here we describe a single-cell protein interaction assay. Single-cell lysates are generated at defined time points and analyzed using single-molecule pull-down, yielding information about dynamic protein complex regulation in vivo. We established the utility of this approach by studying PAR polarity proteins, which mediate polarization of many animal cell types. We uncovered striking regulation of PAR complex composition and stoichiometry during Caenorhabditis elegans zygote polarization, which takes place in less than 20 min. PAR complex dynamics are linked to the cell cycle by Polo-like kinase 1 and govern the movement of PAR proteins to establish polarity. Our results demonstrate an approach to study dynamic biochemical events in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

Probing the interaction of bisintercalating (2,2':6',2″-terpyridine)platinum(II) complexes with glutathione and rabbit plasma.

PubMed

Harper, Benjamin W J; Morris, Thomas T; Gailer, Jürgen; Aldrich-Wright, Janice R

2016-10-01

Platinum(II) complexes have demonstrated considerable success in the treatment of cancer, but severe toxic side effects drive the search for new complexes with increased tumour selectivity and better efficacy. A critical concept that has to be considered in the context of designing novel Pt complexes is their interactions with biomolecules other than DNA. To this end, here the interactions of 16 previously reported bisintercalating (2,2':6',2″-terpyridine)platinum(II) complexes, [{Pt(terpy)} 2 μ-(X)] n+ (where X is a linker) with glutathione (GSH) by means of 1 H and 195 Pt NMR spectroscopy were investigated. The GSH half-life (GSH t 1/2 ) was determined following the incubation of each [{Pt(terpy)} 2 μ-(X)] n+ complex with GSH (8mM). It was observed that complexes 1-7, 11, 12 and 14-16 reacted more rapidly than cisplatin, whereas complexes 8-10, 13 and 17 reacted more slowly (≥200min). There was no apparent correlation between linker length and the GSH t 1/2 . In order to understand these interactions, two complexes: 1 (t 1/2 <1min) and a previously studied 17 [Pt(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)] (56MESS) (GSH t 1/2 =4080min) were incubated with rabbit plasma. A "metallomics" approach was used to analyse plasma for all platinum species at the 5 and the 60min time point and provided results that were congruent with the reaction of the selected Pt complexes with GSH. Our studies demonstrate that the combined application of NMR spectroscopy, cytotoxicity studies and a metallomics approach can contribute to better understand the interaction of [{Pt(terpy)} 2 μ-(X)] n+ complexes with biomolecules to better assess which compounds may be advanced to in vivo studies. Copyright © 2016 Elsevier Inc. All rights reserved.

MIMO: an efficient tool for molecular interaction maps overlap

PubMed Central

2013-01-01

Background Molecular pathways represent an ensemble of interactions occurring among molecules within the cell and between cells. The identification of similarities between molecular pathways across organisms and functions has a critical role in understanding complex biological processes. For the inference of such novel information, the comparison of molecular pathways requires to account for imperfect matches (flexibility) and to efficiently handle complex network topologies. To date, these characteristics are only partially available in tools designed to compare molecular interaction maps. Results Our approach MIMO (Molecular Interaction Maps Overlap) addresses the first problem by allowing the introduction of gaps and mismatches between query and template pathways and permits -when necessary- supervised queries incorporating a priori biological information. It then addresses the second issue by relying directly on the rich graph topology described in the Systems Biology Markup Language (SBML) standard, and uses multidigraphs to efficiently handle multiple queries on biological graph databases. The algorithm has been here successfully used to highlight the contact point between various human pathways in the Reactome database. Conclusions MIMO offers a flexible and efficient graph-matching tool for comparing complex biological pathways. PMID:23672344

Red wine tannins fluidify and precipitate lipid liposomes and bicelles. A role for lipids in wine tasting?

PubMed

Furlan, Aurélien L; Castets, Aurore; Nallet, Frédéric; Pianet, Isabelle; Grélard, Axelle; Dufourc, Erick J; Géan, Julie

2014-05-20

Sensory properties of red wine tannins are bound to complex interactions between saliva proteins, membranes taste receptors of the oral cavity, and lipids or proteins from the human diet. Whereas astringency has been widely studied in terms of tannin-saliva protein colloidal complexes, little is known about interactions between tannins and lipids and their implications in the taste of wine. This study deals with tannin-lipid interactions, by mimicking both oral cavity membranes by micrometric size liposomes and lipid droplets in food by nanometric isotropic bicelles. Deuterium and phosphorus solid-state NMR demonstrated the membrane hydrophobic core disordering promoted by catechin (C), epicatechin (EC), and epigallocatechin gallate (EGCG), the latter appearing more efficient. C and EGCG destabilize isotropic bicelles and convert them into an inverted hexagonal phase. Tannins are shown to be located at the membrane interface and stabilize the lamellar phases. These newly found properties point out the importance of lipids in the complex interactions that happen in the mouth during organoleptic feeling when ingesting tannins.

Template-Based Modeling of Protein-RNA Interactions.

PubMed

Zheng, Jinfang; Kundrotas, Petras J; Vakser, Ilya A; Liu, Shiyong

2016-09-01

Protein-RNA complexes formed by specific recognition between RNA and RNA-binding proteins play an important role in biological processes. More than a thousand of such proteins in human are curated and many novel RNA-binding proteins are to be discovered. Due to limitations of experimental approaches, computational techniques are needed for characterization of protein-RNA interactions. Although much progress has been made, adequate methodologies reliably providing atomic resolution structural details are still lacking. Although protein-RNA free docking approaches proved to be useful, in general, the template-based approaches provide higher quality of predictions. Templates are key to building a high quality model. Sequence/structure relationships were studied based on a representative set of binary protein-RNA complexes from PDB. Several approaches were tested for pairwise target/template alignment. The analysis revealed a transition point between random and correct binding modes. The results showed that structural alignment is better than sequence alignment in identifying good templates, suitable for generating protein-RNA complexes close to the native structure, and outperforms free docking, successfully predicting complexes where the free docking fails, including cases of significant conformational change upon binding. A template-based protein-RNA interaction modeling protocol PRIME was developed and benchmarked on a representative set of complexes.

Regulatory variation: an emerging vantage point for cancer biology.

PubMed

Li, Luolan; Lorzadeh, Alireza; Hirst, Martin

2014-01-01

Transcriptional regulation involves complex and interdependent interactions of noncoding and coding regions of the genome with proteins that interact and modify them. Genetic variation/mutation in coding and noncoding regions of the genome can drive aberrant transcription and disease. In spite of accounting for nearly 98% of the genome comparatively little is known about the contribution of noncoding DNA elements to disease. Genome-wide association studies of complex human diseases including cancer have revealed enrichment for variants in the noncoding genome. A striking finding of recent cancer genome re-sequencing efforts has been the previously underappreciated frequency of mutations in epigenetic modifiers across a wide range of cancer types. Taken together these results point to the importance of dysregulation in transcriptional regulatory control in genesis of cancer. Powered by recent technological advancements in functional genomic profiling, exploration of normal and transformed regulatory networks will provide novel insight into the initiation and progression of cancer and open new windows to future prognostic and diagnostic tools. © 2013 Wiley Periodicals, Inc.

Network biology discovers pathogen contact points in host protein-protein interactomes.

PubMed

Ahmed, Hadia; Howton, T C; Sun, Yali; Weinberger, Natascha; Belkhadir, Youssef; Mukhtar, M Shahid

2018-06-13

In all organisms, major biological processes are controlled by complex protein-protein interactions networks (interactomes), yet their structural complexity presents major analytical challenges. Here, we integrate a compendium of over 4300 phenotypes with Arabidopsis interactome (AI-1 MAIN ). We show that nodes with high connectivity and betweenness are enriched and depleted in conditional and essential phenotypes, respectively. Such nodes are located in the innermost layers of AI-1 MAIN and are preferential targets of pathogen effectors. We extend these network-centric analyses to Cell Surface Interactome (CSI LRR ) and predict its 35 most influential nodes. To determine their biological relevance, we show that these proteins physically interact with pathogen effectors and modulate plant immunity. Overall, our findings contrast with centrality-lethality rule, discover fast information spreading nodes, and highlight the structural properties of pathogen targets in two different interactomes. Finally, this theoretical framework could possibly be applicable to other inter-species interactomes to reveal pathogen contact points.

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

Deng, Ye; Zhang, Ping; Qin, Yujia

When trying to discern network interactions among different species/populations in microbial communities interests have been evoked in recent years, but little information is available about temporal dynamics of microbial network interactions in response to environmental perturbations. We modified the random matrix theory-based network approach to discern network succession in groundwater microbial communities in response to emulsified vegetable oil (EVO) amendment for uranium bioremediation. Groundwater microbial communities from one control and seven monitor wells were analysed with a functional gene array (GeoChip 3.0), and functional molecular ecological networks (fMENs) at different time points were reconstructed. Our results showed that the networkmore » interactions were dramatically altered by EVO amendment. Dynamic and resilient succession was evident: fairly simple at the initial stage (Day 0), increasingly complex at the middle period (Days 4, 17, 31), most complex at Day 80, and then decreasingly complex at a later stage (140–269 days). Unlike previous studies in other habitats, negative interactions predominated in a time-series fMEN, suggesting strong competition among different microbial species in the groundwater systems after EVO injection. In particular, several keystone sulfate-reducing bacteria showed strong negative interactions with their network neighbours. These results provide mechanistic understanding of the decreased phylogenetic diversity during environmental perturbations.« less

Cohesin and related coiled-coil domain-containing complexes physically and functionally connect the dots across the genome

PubMed Central

Poon, Betty P.K

2011-01-01

Interactions between genetic regions located across the genome maintain its three-dimensional organization and function. Recent studies point to key roles for a set of coiled-coil domain-containing complexes (cohibin, cohesin, condensin and monopolin) and related factors in the regulation of DNA-DNA connections across the genome. These connections are critical to replication, recombination, gene expression as well as chromosome segregation. PMID:21822055

Investigation of the interactions of silibinin with 2-hydroxypropyl-β-cyclodextrin through biophysical techniques and computational methods.

PubMed

Kellici, Tahsin F; Ntountaniotis, Dimitrios; Leonis, Georgios; Chatziathanasiadou, Maria; Chatzikonstantinou, Alexandra V; Becker-Baldus, Johanna; Glaubitz, Clemens; Tzakos, Andreas G; Viras, Kyriakos; Chatzigeorgiou, Petros; Tzimas, Stavros; Kefala, Evangelia; Valsami, Georgia; Archontaki, Helen; Papadopoulos, Manthos G; Mavromoustakos, Thomas

2015-03-02

Cyclodextrins (CDs) are a well-known class of supermolecules that have been widely used to protect drugs against conjugation and metabolic inactivation as well as to enhance the aqueous solubility and hence to ameliorate the oral bioavailability of sparingly soluble drug molecules. The hepatoprotectant drug silibinin can be incorporated into CDs, and here we elucidate the interaction between the drug and the host at the molecular level. The complexation product of silibinin with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) is characterized by Differential Scanning Calorimetry, mass spectrometry, solid and liquid high-resolution NMR spectroscopy. The chemical shift changes using (13)C CP/MAS on the complexing of the guest with the host provided significant information on the molecular interactions, and they were in agreement with the 2D NOESY results. These results point out that in both solid and liquid forms, the drug is engulfed and interacts with HP-β-CD in identical manner. Molecular dynamics calculations have been performed to examine the thermodynamic characteristics associated with the silibinin-HP-β-CD interactions and to study the stability of the complex. To approximate the physiological conditions, the aqueous solubility and dissolution characteristics of the complex at pH states simulating those of the upper gastrointestinal tract have been applied. To evaluate the antiproliferative activity of silibinin-HP-β-CD complex comparatively to silibinin in MCF-7 human cancer cells, MTT assays have been performed.

ROSAT HRI and ASCA Observations of the Spiral Galaxy NGC 6946 and its Northeast Complex of Luminous Supernova Remnants

NASA Technical Reports Server (NTRS)

Schlegel, E.; Swank, Jean (Technical Monitor)

2001-01-01

Analysis of 80 ks ASCA (Advanced Satellite for Cosmology and Astrophysics) and 60 ks ROSAT HRI (High Resolution Image) observations of the face-on spiral galaxy NGC 6946 are presented. The ASCA image is the first observation of this galaxy above approximately 2 keV. Diffuse emission may be present in the inner approximately 4' extending to energies above approximately 2-3 keV. In the HRI data, 14 pointlike sources are detected, the brightest two being a source very close to the nucleus and a source to the northeast that corresponds to a luminous complex of interacting supernova remnants (SNRs). We detect a point source that lies approximately 30" west of the SNR complex but with a luminosity -1115 of the SNR complex. None of the point sources show evidence of strong variability; weak variability would escape our detection. The ASCA spectrum of the SNR complex shows evidence for an emission line at approximately 0.9 keV that could be either Ne IX at approximately 0.915 keV or a blend of ion stages of Fe L-shell emission if the continuum is fitted with a power law. However, a two-component, Raymond-Smith thermal spectrum with no lines gives an equally valid continuum fit and may be more physically plausible given the observed spectrum below 3 keV. Adopting this latter model, we derive a density for the SNR complex of 10-35 cm(exp -3), consistent with estimates inferred from optical emission-line ratios. The complex's extraordinary X-ray luminosity may be related more to the high density of the surrounding medium than to a small but intense interaction region where two of the complex's SNRs are apparently colliding.

Network based approaches reveal clustering in protein point patterns

NASA Astrophysics Data System (ADS)

Parker, Joshua; Barr, Valarie; Aldridge, Joshua; Samelson, Lawrence E.; Losert, Wolfgang

2014-03-01

Recent advances in super-resolution imaging have allowed for the sub-diffraction measurement of the spatial location of proteins on the surfaces of T-cells. The challenge is to connect these complex point patterns to the internal processes and interactions, both protein-protein and protein-membrane. We begin analyzing these patterns by forming a geometric network amongst the proteins and looking at network measures, such the degree distribution. This allows us to compare experimentally observed patterns to models. Specifically, we find that the experimental patterns differ from heterogeneous Poisson processes, highlighting an internal clustering structure. Further work will be to compare our results to simulated protein-protein interactions to determine clustering mechanisms.

Molecular modeling reveals binding interface of γ-tubulin with GCP4 and interactions with noscapinoids.

PubMed

Suri, Charu; Joshi, Harish C; Naik, Pradeep Kumar

2015-05-01

The initiation of microtubule assembly within cells is guided by a cone shaped multi-protein complex, γ-tubulin ring complex (γTuRC) containing γ-tubulin and atleast five other γ-tubulin-complex proteins (GCPs), i.e., GCP2, GCP3, GCP4, GCP5, and GCP6. The rim of γTuRC is a ring of γ-tubulin molecules that interacts, via one of its longitudinal interfaces, with GCP2, GCP3, or GCP4 and, via other interface, with α/β-tubulin dimers recruited for the microtubule lattice formation. These interactions however, are not well understood in the absence of crystal structure of functional reconstitution of γTuRC subunits. In this study, we elucidate the atomic interactions between γ-tubulin and GCP4 through computational techniques. We simulated two complexes of γ-tubulin-GCP4 complex (we called dimer1 and dimer2) for 25 ns to obtain a stable complex and calculated the ensemble average of binding free energies of -158.82 and -170.19 kcal/mol for dimer1 and -79.53 and -101.50 kcal/mol for dimer2 using MM-PBSA and MM-GBSA methods, respectively. These highly favourable binding free energy values points to very robust interactions between GCP4 and γ-tubulin. From the results of the free-energy decomposition and the computational alanine scanning calculation, we identified the amino acids crucial for the interaction of γ-tubulin with GCP4, called hotspots. Furthermore, in the endeavour to identify chemical leads that might interact at the interface of γ-tubulin-GCP4 complex; we found a class of compounds based on the plant alkaloid, noscapine that binds with high affinity in a cavity close to γ-tubulin-GCP4 interface compared with previously reported compounds. All noscapinoids displayed stable interaction throughout the simulation, however, most robust interaction was observed for bromo-noscapine followed by noscapine and amino-noscapine. This offers a novel chemical scaffold for γ-tubulin binding drugs near γ-tubulin-GCP4 interface. © 2015 Wiley Periodicals, Inc.

MANAGEMENT OF DIFFUSE POLLUTION IN AGRICULTURAL WATERSHEDS: LESSONS FROM THE MINNESOTA RIVER BASIN. (R825290)

EPA Science Inventory

Abstract

The Minnesota River (Minnesota, USA) receives large non-point source pollutant loads. Complex interactions between agricultural, state agency, environmental groups, and issues of scale make watershed management difficult. Subdividing the basin's 12 major water...

DARC 2.0: Improved Docking and Virtual Screening at Protein Interaction Sites

PubMed Central

Gowthaman, Ragul; Lyskov, Sergey; Karanicolas, John

2015-01-01

Over the past decade, protein-protein interactions have emerged as attractive but challenging targets for therapeutic intervention using small molecules. Due to the relatively flat surfaces that typify protein interaction sites, modern virtual screening tools developed for optimal performance against “traditional” protein targets perform less well when applied instead at protein interaction sites. Previously, we described a docking method specifically catered to the shallow binding modes characteristic of small-molecule inhibitors of protein interaction sites. This method, called DARC (Docking Approach using Ray Casting), operates by comparing the topography of the protein surface when “viewed” from a vantage point inside the protein against the topography of a bound ligand when “viewed” from the same vantage point. Here, we present five key enhancements to DARC. First, we use multiple vantage points to more accurately determine protein-ligand surface complementarity. Second, we describe a new scheme for rapidly determining optimal weights in the DARC scoring function. Third, we incorporate sampling of ligand conformers “on-the-fly” during docking. Fourth, we move beyond simple shape complementarity and introduce a term in the scoring function to capture electrostatic complementarity. Finally, we adjust the control flow in our GPU implementation of DARC to achieve greater speedup of these calculations. At each step of this study, we evaluate the performance of DARC in a “pose recapitulation” experiment: predicting the binding mode of 25 inhibitors each solved in complex with its distinct target protein (a protein interaction site). Whereas the previous version of DARC docked only one of these inhibitors to within 2 Å RMSD of its position in the crystal structure, the newer version achieves this level of accuracy for 12 of the 25 complexes, corresponding to a statistically significant performance improvement (p < 0.001). Collectively then, we find that the five enhancements described here – which together make up DARC 2.0 – lead to dramatically improved speed and performance relative to the original DARC method. PMID:26181386

Interaction of gold nanoparticles with free radicals and their role in enhancing the scavenging activity of ascorbic acid.

PubMed

Razzaq, Humaira; Saira, Farhat; Yaqub, Azra; Qureshi, Rumana; Mumtaz, Misbah; Saleemi, Samia

2016-08-01

The present study investigates the interaction of citrate stabilized gold nanoparticles (12±1.5nm) (GNPs) with free radicals; 1,1-diphenyl-2-picrylhydrazyl (DPPH) stable and electrochemically generated superoxide, O2(-). Different experiments were designed to understand the interaction between GNPs and DPPH by employing cyclic voltammetry, UV-vis spectroscopy and computational chemistry using 6-311G basis set. The increase in heterogeneous rate constant, ksh, of DPPH upon addition of GNPs pointed towards possible complex formation, DPPH-GNPs which were further explained by a model assuming surface adsorption of DPPH on GNPs. Further, the model was validated by studying interaction of GNPs with a biologically important free radical, O2(-). Exciting result in terms of disappearance of anodic peak after GNPs addition confirmed that gold nanoparticles interacted with stable as well as unstable free radicals. Also, the stoichiometry of the most stable complex GNP-DPPH was determined from UV-vis spectroscopy by applying Job's method. The GNP-DPPH complex was found to be active with 46.0% reduction of the IC50 value of standard antioxidant, ascorbic acid (AA), indicating its role in enhancing antioxidant activity. Hence, this study presents a simple and potential approach to enhance the efficiency of natural antioxidants without modifying their structure, or involving the complex functionalization of GNPs with antioxidants. Copyright © 2016. Published by Elsevier B.V.

Nonequilibrium transitions in complex networks: A model of social interaction

NASA Astrophysics Data System (ADS)

Klemm, Konstantin; Eguíluz, Víctor M.; Toral, Raúl; San Miguel, Maxi

2003-02-01

We analyze the nonequilibrium order-disorder transition of Axelrod’s model of social interaction in several complex networks. In a small-world network, we find a transition between an ordered homogeneous state and a disordered state. The transition point is shifted by the degree of spatial disorder of the underlying network, the network disorder favoring ordered configurations. In random scale-free networks the transition is only observed for finite size systems, showing system size scaling, while in the thermodynamic limit only ordered configurations are always obtained. Thus, in the thermodynamic limit the transition disappears. However, in structured scale-free networks, the phase transition between an ordered and a disordered phase is restored.

Computational circular dichroism estimation for point-of-care diagnostics via vortex half-wave retarders

NASA Astrophysics Data System (ADS)

Haider, Shahid A.; Tran, Megan Y.; Wong, Alexander

2018-02-01

Observing the circular dichroism (CD) caused by organic molecules in biological fluids can provide powerful indicators of patient health and provide diagnostic clues for treatment. Methods for this kind of analysis involve tabletop devices that weigh tens of kilograms with costs on the order of tens of thousands of dollars, making them prohibitive in point-of-care diagnostic applications. In an e ort to reduce the size, cost, and complexity of CD estimation systems for point-of-care diagnostics, we propose a novel method for CD estimation that leverages a vortex half-wave retarder in between two linear polarizers and a two-dimensional photodetector array to provide an overall complexity reduction in the system. This enables the measurement of polarization variations across multiple polarizations after they interact with a biological sample, simultaneously, without the need for mechanical actuation. We further discuss design considerations of this methodology in the context of practical applications to point-of-care diagnostics.

Mammalian splicing factor SF1 interacts with SURP domains of U2 snRNP-associated proteins

PubMed Central

Crisci, Angela; Raleff, Flore; Bagdiul, Ivona; Raabe, Monika; Urlaub, Henning; Rain, Jean-Christophe; Krämer, Angela

2015-01-01

Splicing factor 1 (SF1) recognizes the branch point sequence (BPS) at the 3′ splice site during the formation of early complex E, thereby pre-bulging the BPS adenosine, thought to facilitate subsequent base-pairing of the U2 snRNA with the BPS. The 65-kDa subunit of U2 snRNP auxiliary factor (U2AF65) interacts with SF1 and was shown to recruit the U2 snRNP to the spliceosome. Co-immunoprecipitation experiments of SF1-interacting proteins from HeLa cell extracts shown here are consistent with the presence of SF1 in early splicing complexes. Surprisingly almost all U2 snRNP proteins were found associated with SF1. Yeast two-hybrid screens identified two SURP domain-containing U2 snRNP proteins as partners of SF1. A short, evolutionarily conserved region of SF1 interacts with the SURP domains, stressing their role in protein–protein interactions. A reduction of A complex formation in SF1-depleted extracts could be rescued with recombinant SF1 containing the SURP-interaction domain, but only partial rescue was observed with SF1 lacking this sequence. Thus, SF1 can initially recruit the U2 snRNP to the spliceosome during E complex formation, whereas U2AF65 may stabilize the association of the U2 snRNP with the spliceosome at later times. In addition, these findings may have implications for alternative splicing decisions. PMID:26420826

Hydrogen Bonding Interaction between Atmospheric Gaseous Amides and Methanol.

PubMed

Zhao, Hailiang; Tang, Shanshan; Xu, Xiang; Du, Lin

2016-12-30

Amides are important atmospheric organic-nitrogen compounds. Hydrogen bonded complexes of methanol (MeOH) with amides (formamide, N -methylformamide, N , N -dimethylformamide, acetamide, N -methylacetamide and N , N -dimethylacetamide) have been investigated. The carbonyl oxygen of the amides behaves as a hydrogen bond acceptor and the NH group of the amides acts as a hydrogen bond donor. The dominant hydrogen bonding interaction occurs between the carbonyl oxygen and the OH group of methanol as well as the interaction between the NH group of amides and the oxygen of methanol. However, the hydrogen bonds between the CH group and the carbonyl oxygen or the oxygen of methanol are also important for the overall stability of the complexes. Comparable red shifts of the C=O, NH- and OH-stretching transitions were found in these MeOH-amide complexes with considerable intensity enhancement. Topological analysis shows that the electron density at the bond critical points of the complexes fall in the range of hydrogen bonding criteria, and the Laplacian of charge density of the O-H∙∙∙O hydrogen bond slightly exceeds the upper value of the Laplacian criteria. The energy decomposition analysis further suggests that the hydrogen bonding interaction energies can be mainly attributed to the electrostatic, exchange and dispersion components.

Hydrogen Bonding Interaction between Atmospheric Gaseous Amides and Methanol

PubMed Central

Zhao, Hailiang; Tang, Shanshan; Xu, Xiang; Du, Lin

2016-01-01

Amides are important atmospheric organic–nitrogen compounds. Hydrogen bonded complexes of methanol (MeOH) with amides (formamide, N-methylformamide, N,N-dimethylformamide, acetamide, N-methylacetamide and N,N-dimethylacetamide) have been investigated. The carbonyl oxygen of the amides behaves as a hydrogen bond acceptor and the NH group of the amides acts as a hydrogen bond donor. The dominant hydrogen bonding interaction occurs between the carbonyl oxygen and the OH group of methanol as well as the interaction between the NH group of amides and the oxygen of methanol. However, the hydrogen bonds between the CH group and the carbonyl oxygen or the oxygen of methanol are also important for the overall stability of the complexes. Comparable red shifts of the C=O, NH- and OH-stretching transitions were found in these MeOH–amide complexes with considerable intensity enhancement. Topological analysis shows that the electron density at the bond critical points of the complexes fall in the range of hydrogen bonding criteria, and the Laplacian of charge density of the O–H∙∙∙O hydrogen bond slightly exceeds the upper value of the Laplacian criteria. The energy decomposition analysis further suggests that the hydrogen bonding interaction energies can be mainly attributed to the electrostatic, exchange and dispersion components. PMID:28042825

A fraction of neurofibromin interacts with PML bodies in the nucleus of the CCF astrocytoma cell line

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

Godin, Fabienne; Villette, Sandrine; Vallee, Beatrice

Highlights: Black-Right-Pointing-Pointer We validate the use of specific anti-Nf1 antibodies for immunofluorescence studies. Black-Right-Pointing-Pointer We detect Nf1 in the cytoplasm and nucleus of CCF cells. Black-Right-Pointing-Pointer We demonstrate that Nf1 partially colocalizes with PML nuclear bodies. Black-Right-Pointing-Pointer We demonstrate that there is a direct interaction between a fraction of Nf1 and the PML bodies. -- Abstract: Neurofibromatosis type 1 is a common genetic disease that causes nervous system tumors, and cognitive deficits. It is due to mutations within the NF1 gene, which encodes the Nf1 protein. Nf1 has been shown to be involved in the regulation of Ras, cAMP andmore » actin cytoskeleton dynamics. In this study, using immunofluorescence experiments, we have shown a partial nuclear localization of Nf1 in the astrocytoma cell line: CCF and we have demonstrated that Nf1 partially colocalizes with PML (promyelocytic leukemia) nuclear bodies. A direct interaction between Nf1 and the multiprotein complex has further been demonstrated using 'in situ' proximity ligation assay (PLA).« less

Ecological Complexity in a Coffee Agroecosystem: Spatial Heterogeneity, Population Persistence and Biological Control

PubMed Central

Liere, Heidi; Jackson, Doug; Vandermeer, John

2012-01-01

Background Spatial heterogeneity is essential for the persistence of many inherently unstable systems such as predator-prey and parasitoid-host interactions. Since biological interactions themselves can create heterogeneity in space, the heterogeneity necessary for the persistence of an unstable system could be the result of local interactions involving elements of the unstable system itself. Methodology/Principal Findings Here we report on a predatory ladybird beetle whose natural history suggests that the beetle requires the patchy distribution of the mutualism between its prey, the green coffee scale, and the arboreal ant, Azteca instabilis. Based on known ecological interactions and the natural history of the system, we constructed a spatially-explicit model and showed that the clustered spatial pattern of ant nests facilitates the persistence of the beetle populations. Furthermore, we show that the dynamics of the beetle consuming the scale insects can cause the clustered distribution of the mutualistic ants in the first place. Conclusions/Significance From a theoretical point of view, our model represents a novel situation in which a predator indirectly causes a spatial pattern of an organism other than its prey, and in doing so facilitates its own persistence. From a practical point of view, it is noteworthy that one of the elements in the system is a persistent pest of coffee, an important world commodity. This pest, we argue, is kept within limits of control through a complex web of ecological interactions that involves the emergent spatial pattern. PMID:23029061

Computational Fluid Dynamics (CFD) Simulations of a Finned Projectile with Microflaps for Flow Control

DTIC Science & Technology

2016-04-01

fields associated with these control mechanisms for US Army weapons are complex, involving 3-dimensional (3-D) shock- boundary layer interactions...distribution over the rear finned section and thus produce control forces and moments. Dykes et al.6 used a flat - plate fin interaction design of...cells—tetrahedrals, triangular prisms, and pyramids—were used in the mesh. Grid points shown in Fig. 3a were clustered in the boundary layer region

Linking market interaction intensity of 3D Ising type financial model with market volatility

NASA Astrophysics Data System (ADS)

Fang, Wen; Ke, Jinchuan; Wang, Jun; Feng, Ling

2016-11-01

Microscopic interaction models in physics have been used to investigate the complex phenomena of economic systems. The simple interactions involved can lead to complex behaviors and help the understanding of mechanisms in the financial market at a systemic level. This article aims to develop a financial time series model through 3D (three-dimensional) Ising dynamic system which is widely used as an interacting spins model to explain the ferromagnetism in physics. Through Monte Carlo simulations of the financial model and numerical analysis for both the simulation return time series and historical return data of Hushen 300 (HS300) index in Chinese stock market, we show that despite its simplicity, this model displays stylized facts similar to that seen in real financial market. We demonstrate a possible underlying link between volatility fluctuations of real stock market and the change in interaction strengths of market participants in the financial model. In particular, our stochastic interaction strength in our model demonstrates that the real market may be consistently operating near the critical point of the system.

Insight to the Interaction of the Dihydrolipoamide Acetyltransferase (E2) Core with the Peripheral Components in the Escherichia coli Pyruvate Dehydrogenase Complex via Multifaceted Structural Approaches*

PubMed Central

Chandrasekhar, Krishnamoorthy; Wang, Junjie; Arjunan, Palaniappa; Sax, Martin; Park, Yun-Hee; Nemeria, Natalia S.; Kumaran, Sowmini; Song, Jaeyoung; Jordan, Frank; Furey, William

2013-01-01

Multifaceted structural approaches were undertaken to investigate interaction of the E2 component with E3 and E1 components from the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc), as a representative of the PDHc from Gram-negative bacteria. The crystal structure of E3 at 2.5 Å resolution reveals similarity to other E3 structures and was an important starting point for understanding interaction surfaces between E3 and E2. Biochemical studies revealed that R129E-E2 and R150E-E2 substitutions in the peripheral subunit-binding domain (PSBD) of E2 greatly diminished PDHc activity, affected interactions with E3 and E1 components, and affected reductive acetylation of E2. Because crystal structures are unavailable for any complete E2-containing complexes, peptide-specific hydrogen/deuterium exchange mass spectrometry was used to identify loci of interactions between 3-lipoyl E2 and E3. Two peptides from the PSBD, including Arg-129, and three peptides from E3 displayed statistically significant reductions in deuterium uptake resulting from interaction between E3 and E2. Of the peptides identified on E3, two were from the catalytic site, and the third was from the interface domain, which for all known E3 structures is believed to interact with the PSBD. NMR clearly demonstrates that there is no change in the lipoyl domain structure on complexation with E3. This is the first instance where the entire wild-type E2 component was employed to understand interactions with E3. A model for PSBD-E3 binding was independently constructed and found to be consistent with the importance of Arg-129, as well as revealing other electrostatic interactions likely stabilizing this complex. PMID:23580650

Insight to the interaction of the dihydrolipoamide acetyltransferase (E2) core with the peripheral components in the Escherichia coli pyruvate dehydrogenase complex via multifaceted structural approaches.

PubMed

Chandrasekhar, Krishnamoorthy; Wang, Junjie; Arjunan, Palaniappa; Sax, Martin; Park, Yun-Hee; Nemeria, Natalia S; Kumaran, Sowmini; Song, Jaeyoung; Jordan, Frank; Furey, William

2013-05-24

Multifaceted structural approaches were undertaken to investigate interaction of the E2 component with E3 and E1 components from the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc), as a representative of the PDHc from Gram-negative bacteria. The crystal structure of E3 at 2.5 Å resolution reveals similarity to other E3 structures and was an important starting point for understanding interaction surfaces between E3 and E2. Biochemical studies revealed that R129E-E2 and R150E-E2 substitutions in the peripheral subunit-binding domain (PSBD) of E2 greatly diminished PDHc activity, affected interactions with E3 and E1 components, and affected reductive acetylation of E2. Because crystal structures are unavailable for any complete E2-containing complexes, peptide-specific hydrogen/deuterium exchange mass spectrometry was used to identify loci of interactions between 3-lipoyl E2 and E3. Two peptides from the PSBD, including Arg-129, and three peptides from E3 displayed statistically significant reductions in deuterium uptake resulting from interaction between E3 and E2. Of the peptides identified on E3, two were from the catalytic site, and the third was from the interface domain, which for all known E3 structures is believed to interact with the PSBD. NMR clearly demonstrates that there is no change in the lipoyl domain structure on complexation with E3. This is the first instance where the entire wild-type E2 component was employed to understand interactions with E3. A model for PSBD-E3 binding was independently constructed and found to be consistent with the importance of Arg-129, as well as revealing other electrostatic interactions likely stabilizing this complex.

A 3D complex containing novel 2D Cu{sup II}-azido layers: Structure, magnetic properties and effects of 'Non-innocent' reagent

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

Gao, Xue-Miao; Guo, Qian; Zhao, Jiong-Peng, E-mail: horryzhao@yahoo.com

A novel copper-azido coordination polymer, [Cu{sub 2}(N{sub 3}){sub 3}(L)]{sub n} (1, HL=pyrazine-2-carboxylic acid), has been synthesized by hydrothermal reaction with 'Non-innocent' reagent in the aqueous solution. In the reaction system, Cu{sup II} ions are avoided to reduce to Cu{sup I} ions due to the existence of Nd{sup III}. It is found that the complex is a 3D structure based on two double EO azido bridged trimmers and octahedron Cu{sup II} ions, in which the azide ligands take on EO and {mu}{sub 1,1,3} mode to form Cu{sup II}-azido 2D layers, furthermore L ligands pillar 2D layers into an infinite 3D frameworkmore » with the Schlaefli symbol of {l_brace}4;6{sup 2}{r_brace}4{l_brace}4{sup 2};6{sup 12};8{sup 10};10{sup 4}{r_brace}{l_brace}4{sup 2};6{sup 4}{r_brace}. Magnetic studies revealed that the interactions between the Cu{sup II} ions in the trimmer are ferromagnetic for the Cu-N-Cu angle nearly 98 Degree-Sign , while the interactions between the trimmer and octahedron Cu{sup II} ion are antiferromgantic and result in an antiferromagnetic state. - Graphical abstract: A 3D complex containing novel 2D Cu{sup II}-azido layers, [Cu{sub 2}(N{sub 3}){sub 3}(L)]{sub n} (HL=pyrazine-2-carboxylic acid), was synthesized by hydrothermal reaction and exhibit interesting structure and magnetic properties. Highlights: Black-Right-Pointing-Pointer 'Non-innocent' reagents plays a key role in the process of formation of this complex. Black-Right-Pointing-Pointer 2D layer is formed only by Cu{sup II} ions and azido ligands. Black-Right-Pointing-Pointer Pyrazine-2-carboxylate ligands reinforce 2D layers and pillar them into an infinite 3D framework. Black-Right-Pointing-Pointer Magnetic study indicates that alternating FM-AF coupling exists in the complex.« less

Quantum critical point underlying the pseudogap state in underdoped cuprate superconductors

NASA Astrophysics Data System (ADS)

Pepin, Catherine

2014-03-01

Cuprate superconductors rank among the most complex materials that are known in the universe. Faced with this complexity, scientists have adopted two types of approaches. In a bottom up approach, one considers that strong correlations occur at a high energy scale of roughly 1 eV upon very strong Coulomb interactions. In the top down approach one considers that one universal singularity at very low temperatures is responsible for complexity of the phase diagram. In this talk we will argue that the strong quantum fluctuations experienced at the proximity to a anti-ferromagnetic Quantum Critical Point (QCP) is responsible for a cascade of phase transitions in the charge and superconducting channels. We will discuss in this context the emergence of the pseudo-gap and charge order modulations. Symmetries and relations to experimental observations will be addressed. Work done in collaboration with K.B. Efetov (Bochum) and H. Meier (Yale).

A distal point mutation in the streptavidin-biotin complex preserves structure but diminishes binding affinity: experimental evidence of electronic polarization effects?

PubMed

Baugh, Loren; Le Trong, Isolde; Cerutti, David S; Gülich, Susanne; Stayton, Patrick S; Stenkamp, Ronald E; Lybrand, Terry P

2010-06-08

We have identified a distal point mutation in streptavidin that causes a 1000-fold reduction in biotin binding affinity without disrupting the equilibrium complex structure. The F130L mutation creates a small cavity occupied by a water molecule; however, all neighboring side chain positions are preserved, and protein-biotin hydrogen bonds are unperturbed. Molecular dynamics simulations reveal a reduced mobility of biotin binding residues but no observable destabilization of protein-ligand interactions. Our combined structural and computational studies suggest that the additional water molecule may affect binding affinity through an electronic polarization effect that impacts the highly cooperative hydrogen bonding network in the biotin binding pocket.

Mechanisms underlying changes in indomethacin solubility with local anesthetics and related basic additives

NASA Astrophysics Data System (ADS)

Shimada, Yohsuke; Tateuchi, Ryo; Chatani, Hitoshi; Goto, Satoru

2018-03-01

Indomethacin (IND), an acidic nonsteroidal anti-inflammatory drug, and lidocaine (LID), a local anesthetic (LA), form a eutectic complex when mixed, with a lower melting point. The aqueous solubility of the mixture is greater than that of IND or LID alone, improving the bioavailability of IND. Therefore, IND and LID can be used to model changes in efficacy caused by physicochemical interactions between drugs. In this study, the intermolecular interactions between IND and structurally similar LAs were examined by measuring solubility and analyzing thermodynamics using differential scanning calorimetry. The results indicate that the solubility of IND (log S'IND) varies with LA hydrophobicity. Reductions in melting point resulting from mixing IND and LAs contributed to changes in IND solubility, attributable to direct intermolecular interactions between IND and the LAs. In addition, binding energy of IND-LA as in water was calculated, and the values were correlating with the solubility of IND in experiments. Understanding these interactions will help address some of the problems encountered in polypharmacy.

GREEN: A program package for docking studies in rational drug design

NASA Astrophysics Data System (ADS)

Tomioka, Nobuo; Itai, Akiko

1994-08-01

A program package, GREEN, has been developed that enables docking studies between ligand molecules and a protein molecule. Based on the structure of the protein molecule, the physical and chemical environment of the ligand-binding site is expressed as three-dimensional grid-point data. The grid-point data are used for the real-time evaluation of the protein-ligand interaction energy, as well as for the graphical representation of the binding-site environment. The interactive docking operation is facilitated by various built-in functions, such as energy minimization, energy contribution analysis and logging of the manipulation trajectory. Interactive modeling functions are incorporated for designing new ligand molecules while considering the binding-site environment and the protein-ligand interaction. As an example of the application of GREEN, a docking study is presented on the complex between trypsin and a synthetic trypsin inhibitor. The program package will be useful for rational drug design, based on the 3D structure of the target protein.

Dynamics of nonautonomous rogue waves in Bose-Einstein condensate

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

Zhao, Li-Chen, E-mail: zhaolichen3@163.com

2013-02-15

We study rogue waves of Bose-Einstein condensate (BEC) analytically in a time-dependent harmonic trap with a complex potential. Properties of the nonautonomous rogue waves are investigated analytically. It is reported that there are possibilities to 'catch' rogue waves through manipulating nonlinear interaction properly. The results provide many possibilities to manipulate rogue waves experimentally in a BEC system. - Highlights: Black-Right-Pointing-Pointer One more generalized rogue wave solutions are presented. Black-Right-Pointing-Pointer Present one possible way to catch a rouge wave. Black-Right-Pointing-Pointer Properties of rogue waves are investigated analytically for the first time. Black-Right-Pointing-Pointer Provide many possibilities to manipulate rogue waves in BEC.

Template-Based Modeling of Protein-RNA Interactions

PubMed Central

Zheng, Jinfang; Kundrotas, Petras J.; Vakser, Ilya A.

2016-01-01

Protein-RNA complexes formed by specific recognition between RNA and RNA-binding proteins play an important role in biological processes. More than a thousand of such proteins in human are curated and many novel RNA-binding proteins are to be discovered. Due to limitations of experimental approaches, computational techniques are needed for characterization of protein-RNA interactions. Although much progress has been made, adequate methodologies reliably providing atomic resolution structural details are still lacking. Although protein-RNA free docking approaches proved to be useful, in general, the template-based approaches provide higher quality of predictions. Templates are key to building a high quality model. Sequence/structure relationships were studied based on a representative set of binary protein-RNA complexes from PDB. Several approaches were tested for pairwise target/template alignment. The analysis revealed a transition point between random and correct binding modes. The results showed that structural alignment is better than sequence alignment in identifying good templates, suitable for generating protein-RNA complexes close to the native structure, and outperforms free docking, successfully predicting complexes where the free docking fails, including cases of significant conformational change upon binding. A template-based protein-RNA interaction modeling protocol PRIME was developed and benchmarked on a representative set of complexes. PMID:27662342

Textile Pressure Mapping Sensor for Emotional Touch Detection in Human-Robot Interaction

PubMed Central

Cruz Zurian, Heber; Atefi, Seyed Reza; Seoane Martinez, Fernando; Lukowicz, Paul

2017-01-01

In this paper, we developed a fully textile sensing fabric for tactile touch sensing as the robot skin to detect human-robot interactions. The sensor covers a 20-by-20 cm2 area with 400 sensitive points and samples at 50 Hz per point. We defined seven gestures which are inspired by the social and emotional interactions of typical people to people or pet scenarios. We conducted two groups of mutually blinded experiments, involving 29 participants in total. The data processing algorithm first reduces the spatial complexity to frame descriptors, and temporal features are calculated through basic statistical representations and wavelet analysis. Various classifiers are evaluated and the feature calculation algorithms are analyzed in details to determine each stage and segments’ contribution. The best performing feature-classifier combination can recognize the gestures with a 93.3% accuracy from a known group of participants, and 89.1% from strangers. PMID:29120389

Textile Pressure Mapping Sensor for Emotional Touch Detection in Human-Robot Interaction.

PubMed

Zhou, Bo; Altamirano, Carlos Andres Velez; Zurian, Heber Cruz; Atefi, Seyed Reza; Billing, Erik; Martinez, Fernando Seoane; Lukowicz, Paul

2017-11-09

In this paper, we developed a fully textile sensing fabric for tactile touch sensing as the robot skin to detect human-robot interactions. The sensor covers a 20-by-20 cm 2 area with 400 sensitive points and samples at 50 Hz per point. We defined seven gestures which are inspired by the social and emotional interactions of typical people to people or pet scenarios. We conducted two groups of mutually blinded experiments, involving 29 participants in total. The data processing algorithm first reduces the spatial complexity to frame descriptors, and temporal features are calculated through basic statistical representations and wavelet analysis. Various classifiers are evaluated and the feature calculation algorithms are analyzed in details to determine each stage and segments' contribution. The best performing feature-classifier combination can recognize the gestures with a 93 . 3 % accuracy from a known group of participants, and 89 . 1 % from strangers.

Periodontal and inflammatory bowel diseases: Is there evidence of complex pathogenic interactions?

PubMed

Lira-Junior, Ronaldo; Figueredo, Carlos Marcelo

2016-09-21

Periodontal disease and inflammatory bowel disease (IBD) are both chronic inflammatory diseases. Their pathogenesis is mediated by a complex interplay between a dysbiotic microbiota and the host immune-inflammatory response, and both are influenced by genetic and environmental factors. This review aimed to provide an overview of the evidence dealing with a possible pathogenic interaction between periodontal disease and IBD. There seems to be an increased prevalence of periodontal disease in patients with IBD when compared to healthy controls, probably due to changes in the oral microbiota and a higher inflammatory response. Moreover, the induction of periodontitis seems to result in gut dysbiosis and altered gut epithelial cell barrier function, which might contribute to the pathogenesis of IBD. Considering the complexity of both periodontal disease and IBD, it is very challenging to understand the possible pathways involved in their coexistence. In conclusion, this review points to a complex pathogenic interaction between periodontal disease and IBD, in which one disease might alter the composition of the microbiota and increase the inflammatory response related to the other. However, we still need more data derived from human studies to confirm results from murine models. Thus, mechanistic studies are definitely warranted to clarify this possible bidirectional association.

Atomic Resolution Modeling of the Ferredoxin:[FeFe] Hydrogenase Complex from Chlamydomonas reinhardtii

PubMed Central

Chang, Christopher H.; King, Paul W.; Ghirardi, Maria L.; Kim, Kwiseon

2007-01-01

The [FeFe] hydrogenases HydA1 and HydA2 in the green alga Chlamydomonas reinhardtii catalyze the final reaction in a remarkable metabolic pathway allowing this photosynthetic organism to produce H2 from water in the chloroplast. A [2Fe-2S] ferredoxin is a critical branch point in electron flow from Photosystem I toward a variety of metabolic fates, including proton reduction by hydrogenases. To better understand the binding determinants involved in ferredoxin:hydrogenase interactions, we have modeled Chlamydomonas PetF1 and HydA2 based on amino-acid sequence homology, and produced two promising electron-transfer model complexes by computational docking. To characterize these models, quantitative free energy calculations at atomic resolution were carried out, and detailed analysis of the interprotein interactions undertaken. The protein complex model we propose for ferredoxin:HydA2 interaction is energetically favored over the alternative candidate by 20 kcal/mol. This proposed model of the electron-transfer complex between PetF1 and HydA2 permits a more detailed view of the molecular events leading up to H2 evolution, and suggests potential mutagenic strategies to modulate electron flow to HydA2. PMID:17660315

Atomic resolution modeling of the ferredoxin:[FeFe] hydrogenase complex from Chlamydomonas reinhardtii.

PubMed

Chang, Christopher H; King, Paul W; Ghirardi, Maria L; Kim, Kwiseon

2007-11-01

The [FeFe] hydrogenases HydA1 and HydA2 in the green alga Chlamydomonas reinhardtii catalyze the final reaction in a remarkable metabolic pathway allowing this photosynthetic organism to produce H(2) from water in the chloroplast. A [2Fe-2S] ferredoxin is a critical branch point in electron flow from Photosystem I toward a variety of metabolic fates, including proton reduction by hydrogenases. To better understand the binding determinants involved in ferredoxin:hydrogenase interactions, we have modeled Chlamydomonas PetF1 and HydA2 based on amino-acid sequence homology, and produced two promising electron-transfer model complexes by computational docking. To characterize these models, quantitative free energy calculations at atomic resolution were carried out, and detailed analysis of the interprotein interactions undertaken. The protein complex model we propose for ferredoxin:HydA2 interaction is energetically favored over the alternative candidate by 20 kcal/mol. This proposed model of the electron-transfer complex between PetF1 and HydA2 permits a more detailed view of the molecular events leading up to H(2) evolution, and suggests potential mutagenic strategies to modulate electron flow to HydA2.

Genome-Wide Protein Interaction Screens Reveal Functional Networks Involving Sm-Like Proteins

PubMed Central

Fromont-Racine, Micheline; Mayes, Andrew E.; Brunet-Simon, Adeline; Rain, Jean-Christophe; Colley, Alan; Dix, Ian; Decourty, Laurence; Joly, Nicolas; Ricard, Florence; Beggs, Jean D.

2000-01-01

A set of seven structurally related Sm proteins forms the core of the snRNP particles containing the spliceosomal U1, U2, U4 and U5 snRNAs. A search of the genomic sequence of Saccharomyces cerevisiae has identified a number of open reading frames that potentially encode structurally similar proteins termed Lsm (Like Sm) proteins. With the aim of analysing all possible interactions between the Lsm proteins and any protein encoded in the yeast genome, we performed exhaustive and iterative genomic two-hybrid screens, starting with the Lsm proteins as baits. Indeed, extensive interactions amongst eight Lsm proteins were found that suggest the existence of a Lsm complex or complexes. These Lsm interactions apparently involve the conserved Sm domain that also mediates interactions between the Sm proteins. The screens also reveal functionally significant interactions with splicing factors, in particular with Prp4 and Prp24, compatible with genetic studies and with the reported association of Lsm proteins with spliceosomal U6 and U4/U6 particles. In addition, interactions with proteins involved in mRNA turnover, such as Mrt1, Dcp1, Dcp2 and Xrn1, point to roles for Lsm complexes in distinct RNA metabolic processes, that are confirmed in independent functional studies. These results provide compelling evidence that two-hybrid screens yield functionally meaningful information about protein–protein interactions and can suggest functions for uncharacterized proteins, especially when they are performed on a genome-wide scale. PMID:10900456

Zein/caseinate/pectin complex nanoparticles: Formation and characterization.

PubMed

Chang, Chao; Wang, Taoran; Hu, Qiaobin; Luo, Yangchao

2017-11-01

In this study, pectin was used as coating material to form zein/caseinate/pectin complex nanoparticles through pH adjustment and heating treatment for potential oral delivery applications. The preparation conditions were studied by applying heating treatment at different pHs, either the isoelectric point of zein (pH 6.2) or caseinate (pH 4.6), or consecutively at both pHs. The particulate characteristics, including particle size, polydispersity index, and zeta potential were monitored for complex nanoparticles formed under different preparation conditions. The complex nanoparticles generally exhibited particle size smaller than 200nm with narrow distribution, spherical shape, and strong negative charge. Fourier transform infrared and fluorescence spectroscopy revealed that hydrophobic interactions and hydrogen bonds were involved in the formation of complex nanoparticles, in addition to electrostatic interactions. Fresh colloidal dispersion and freeze-dried powders varied in their morphology, depending on their preparation conditions. Our results suggested that heating pH and sequence significantly affected the morphology of complex nanoparticles, and pectin coating exerted stabilization effect under simulated gastrointestinal conditions. The present study provides insight into the formation of protein/polysaccharide complex nanoparticles under different preparation conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

A chromatin remodelling complex that loads cohesin onto human chromosomes

NASA Astrophysics Data System (ADS)

Hakimi, Mohamed-Ali; Bochar, Daniel A.; Schmiesing, John A.; Dong, Yuanshu; Barak, Orr G.; Speicher, David W.; Yokomori, Kyoko; Shiekhattar, Ramin

2002-08-01

Nucleosomal DNA is arranged in a higher-order structure that presents a barrier to most cellular processes involving protein DNA interactions. The cellular machinery involved in sister chromatid cohesion, the cohesin complex, also requires access to the nucleosomal DNA to perform its function in chromosome segregation. The machineries that provide this accessibility are termed chromatin remodelling factors. Here, we report the isolation of a human ISWI (SNF2h)-containing chromatin remodelling complex that encompasses components of the cohesin and NuRD complexes. We show that the hRAD21 subunit of the cohesin complex directly interacts with the ATPase subunit SNF2h. Mapping of hRAD21, SNF2h and Mi2 binding sites by chromatin immunoprecipitation experiments reveals the specific association of these three proteins with human DNA elements containing Alu sequences. We find a correlation between modification of histone tails and association of the SNF2h/cohesin complex with chromatin. Moreover, we show that the association of the cohesin complex with chromatin can be regulated by the state of DNA methylation. Finally, we present evidence pointing to a role for the ATPase activity of SNF2h in the loading of hRAD21 on chromatin.

Iron chalcogenide superconductors at high magnetic fields

PubMed Central

Lei, Hechang; Wang, Kefeng; Hu, Rongwei; Ryu, Hyejin; Abeykoon, Milinda; Bozin, Emil S; Petrovic, Cedomir

2012-01-01

Iron chalcogenide superconductors have become one of the most investigated superconducting materials in recent years due to high upper critical fields, competing interactions and complex electronic and magnetic phase diagrams. The structural complexity, defects and atomic site occupancies significantly affect the normal and superconducting states in these compounds. In this work we review the vortex behavior, critical current density and high magnetic field pair-breaking mechanism in iron chalcogenide superconductors. We also point to relevant structural features and normal-state properties. PMID:27877518

Inception of self-interacting dark matter with dark charge conjugation symmetry

DOE PAGES

Ma, Ernest

2017-07-04

A new understanding of the stability of self-interacting dark matter is pointed out, based on the simplest spontaneously broken Abelian gauge model with one complex scalar and one Dirac fermion. The key is the imposition of dark charge conjugation symmetry. It allows the possible existence of two stable particles: the Dirac fermion and the vector gauge boson which acts as a light mediator for the former's self-interaction. Since this light mediator does not decay, it avoids the strong cosmological constraints recently obtained for all such models where the light mediator decays into standard-model particles.

GPU-enabled molecular dynamics simulations of ankyrin kinase complex

NASA Astrophysics Data System (ADS)

Gautam, Vertika; Chong, Wei Lim; Wisitponchai, Tanchanok; Nimmanpipug, Piyarat; Zain, Sharifuddin M.; Rahman, Noorsaadah Abd.; Tayapiwatana, Chatchai; Lee, Vannajan Sanghiran

2014-10-01

The ankyrin repeat (AR) protein can be used as a versatile scaffold for protein-protein interactions. It has been found that the heterotrimeric complex between integrin-linked kinase (ILK), PINCH, and parvin is an essential signaling platform, serving as a convergence point for integrin and growth-factor signaling and regulating cell adhesion, spreading, and migration. Using ILK-AR with high affinity for the PINCH1 as our model system, we explored a structure-based computational protocol to probe and characterize binding affinity hot spots at protein-protein interfaces. In this study, the long time scale dynamics simulations with GPU accelerated molecular dynamics (MD) simulations in AMBER12 have been performed to locate the hot spots of protein-protein interaction by the analysis of the Molecular Mechanics-Poisson-Boltzmann Surface Area/Generalized Born Solvent Area (MM-PBSA/GBSA) of the MD trajectories. Our calculations suggest good binding affinity of the complex and also the residues critical in the binding.

Balancing Management and Leadership in Complex Health Systems Comment on "Management Matters: A Leverage Point for Health Systems Strengthening in Global Health".

PubMed

Kwamie, Aku

2015-08-14

Health systems, particularly those in low- and middle-income countries (LMICs), need stronger management and leadership capacities. Management and leadership are not synonymous, yet should be considered together as there can be too much of one and not enough of the other. In complex adaptive health systems, the multiple interactions and relationships between people and elements of the system mean that management and leadership, so often treated as domains of the individual, are additionally systemic phenomena, emerging from these relational interactions. This brief commentary notes some significant implications for how we can support capacity strengthening interventions for complex management and leadership. These would necessarily move away from competency-based models focused on training for individuals, and would rather encompass longer-term initiatives explicitly focused on systemic goals of accountability, innovation, and learning. © 2015 by Kerman University of Medical Sciences.

[19F]fluorine nuclear-magnetic-resonance study of the interaction of difluoro-oxaloacetate with aspartate transaminase.

PubMed Central

Briley, P A; Eisenthal, R; Harrison, R; Smith, G D

1977-01-01

Difluoro-oxaloacetate interacts with the aldimine form of aspartate transaminase to give a complex, the dissociation constant of which has been determined spectrophotometrically and by 19F n.m.r. (nuclear magnetic resonance). The 19F n.m.r. line-width-pH and chemical-shift-pH profiles of difluoro-oxaloacetate in the presence of the aldimine form of the enzyme both show inflexion points in the pH5 and pH8 regions, which may arise from variations in the binding of difluoro-oxaloacetate as specific groups on the enzyme are successively protonated. Difluoro-oxaloacetate also interacts with apoenzyme to form a complex, the dissociation constant of which was determined by 19F n.m.r. The 19F n.m.r. line-width-pH and chemical-shift-pH profiles of difluoro-oxaloacetate in the presence of apoenzyme show a single inflexion point in the region of pH8. The absence, in this case, of an inflexion in the pH5 region indicates that the latter, present in the corresponding profiles for the aldimine form of the enzyme, results from ionization of an enzyme group associated with the pyridoxal phosphate cofactor. PMID:17399

The interaction of MnH(X 7Σ+) with He: Ab initio potential energy surface and bound states

NASA Astrophysics Data System (ADS)

Turpin, Florence; Halvick, Philippe; Stoecklin, Thierry

2010-06-01

The potential energy surface of the ground state of the He-MnH(X Σ7+) van der Waals complex is presented. Within the supermolecular approach of intermolecular energy calculations, a grid of ab initio points was computed at the multireference configuration interaction level using the aug-cc-pVQZ basis set for helium and hydrogen and the relativistic aug-cc-pVQZ-DK basis set for manganese. The potential energy surface was then fitted to a global analytical form which main features are discussed. As a first application of this potential energy surface, we present accurate calculations of bound energy levels of the H3e-MnH and H4e-MnH complexes.

The interaction of MnH(X 7Sigma+) with He: ab initio potential energy surface and bound states.

PubMed

Turpin, Florence; Halvick, Philippe; Stoecklin, Thierry

2010-06-07

The potential energy surface of the ground state of the He-MnH(X (7)Sigma(+)) van der Waals complex is presented. Within the supermolecular approach of intermolecular energy calculations, a grid of ab initio points was computed at the multireference configuration interaction level using the aug-cc-pVQZ basis set for helium and hydrogen and the relativistic aug-cc-pVQZ-DK basis set for manganese. The potential energy surface was then fitted to a global analytical form which main features are discussed. As a first application of this potential energy surface, we present accurate calculations of bound energy levels of the (3)He-MnH and (4)He-MnH complexes.

Entering AN ERA of Synthesis of Modeling

NASA Astrophysics Data System (ADS)

Guerin, Stephen

First, I believe we're entering an era of synthesis of modeling. Over the past 20 years, we've seen the proliferation of many isolated complex systems models. I think we now need tools for researchers, policy makers and the public to share models. Sharing could happen by stacking different layers of spatial agent-based models in geographic information systems and projecting interactive visualization out onto shared surfaces. Further, we need to make model authoring tools much more accessible to the point where motivated policy makers can author on their own. With the increased ability to author and share models, I believe this will allow us to scale our research to understand and manage the many interacting systems that make up our complex world...

Fast generation of complex modulation video holograms using temporal redundancy compression and hybrid point-source/wave-field approaches

NASA Astrophysics Data System (ADS)

Gilles, Antonin; Gioia, Patrick; Cozot, Rémi; Morin, Luce

2015-09-01

The hybrid point-source/wave-field method is a newly proposed approach for Computer-Generated Hologram (CGH) calculation, based on the slicing of the scene into several depth layers parallel to the hologram plane. The complex wave scattered by each depth layer is then computed using either a wave-field or a point-source approach according to a threshold criterion on the number of points within the layer. Finally, the complex waves scattered by all the depth layers are summed up in order to obtain the final CGH. Although outperforming both point-source and wave-field methods without producing any visible artifact, this approach has not yet been used for animated holograms, and the possible exploitation of temporal redundancies has not been studied. In this paper, we propose a fast computation of video holograms by taking into account those redundancies. Our algorithm consists of three steps. First, intensity and depth data of the current 3D video frame are extracted and compared with those of the previous frame in order to remove temporally redundant data. Then the CGH pattern for this compressed frame is generated using the hybrid point-source/wave-field approach. The resulting CGH pattern is finally transmitted to the video output and stored in the previous frame buffer. Experimental results reveal that our proposed method is able to produce video holograms at interactive rates without producing any visible artifact.

A New Theoretical Foundation for Relationship-centered Care

PubMed Central

Suchman, Anthony L

2006-01-01

Relationship-centered care (RCC) is a clinical philosophy that stresses partnership, careful attention to relational process, shared decision-making, and self-awareness. A new complexity-inspired theory of human interaction called complex responsive processes of relating (CRPR) offers strong theoretical confirmation for the principles and practices of RCC, and thus may be of interest to communications researchers and reflective practitioners. It points out the nonlinear nature of human interaction and accounts for the emergence of self-organizing patterns of meaning (e.g., themes or ideas) and patterns of relating (e.g., power relations). CRPR offers fresh new perspectives on the mind, self, communication, and organizations. For observers of interaction, it focuses attention on the nature of moment-to-moment relational process, the value of difference and diversity, and the importance of authentic and responsive participation, thus closely corresponding to and providing theoretical support for RCC. PMID:16405709

"Accepting Emotional Complexity": A Socio-Constructivist Perspective on the Role of Emotions in the Mathematics Classroom

ERIC Educational Resources Information Center

Eynde, Peter Op't; De Corte, Erik; Verschaffel, Lieven

2006-01-01

A socio-constructivist account of learning and emotions stresses the situatedness of every learning activity and points to the close interactions between cognitive, conative and affective factors in students' learning and problem solving. Emotions are perceived as being constituted by the dynamic interplay of cognitive, physiological, and…

Analysis of macromolecules, ligands and macromolecule-ligand complexes

DOEpatents

Von Dreele, Robert B [Los Alamos, NM

2008-12-23

A method for determining atomic level structures of macromolecule-ligand complexes through high-resolution powder diffraction analysis and a method for providing suitable microcrystalline powder for diffraction analysis are provided. In one embodiment, powder diffraction data is collected from samples of polycrystalline macromolecule and macromolecule-ligand complex and the refined structure of the macromolecule is used as an approximate model for a combined Rietveld and stereochemical restraint refinement of the macromolecule-ligand complex. A difference Fourier map is calculated and the ligand position and points of interaction between the atoms of the macromolecule and the atoms of the ligand can be deduced and visualized. A suitable polycrystalline sample of macromolecule-ligand complex can be produced by physically agitating a mixture of lyophilized macromolecule, ligand and a solvent.

A combined molecular dynamics simulation and quantum mechanics study on mercaptopurine interaction with the cucurbit [6,7] urils: Analysis of electronic structure

NASA Astrophysics Data System (ADS)

Zaboli, Maryam; Raissi, Heidar

2018-01-01

In the current study, the probability of complex formation between mercaptopurine drug with cucurbit[6]urils and cucurbit[7]urils has been investigated. The calculations for geometry optimization of complexes have been carried out by means of DFT (B3LYP), DFT-D (B3LYP-D) and M06-2X methods. The Atoms In Molecules (AIM), Natural Bond Orbital (NBO), NMR, the density of states (DOSs) and frontier molecular orbital (MO) analyses have been done on the inclusion complexes. In addition, the UV-Vis spectra of the first eight states have been obtained by CAM-B3LYP/TD-DFT calculation. The obtained results of the complexation process reveal that CB[7]-DRG complexes are more favorable than that of CB[6]-DRG interactions. Furthermore, our theoretical results show that configurations III and I are the most stable configurations related to the CB[6]/DRG and CB[7]/DRG interactions, respectively. The positive ∇2ρ(r) and HC values at the bond critical points indicate that exist the weak H-bonds between CB[6] and CB[7] with H atoms of the drug molecule. The obtained negative binding energy values of CB[7]-DRG interaction in solution phase show the stability of these complexes in the aqueous medium. Also, all of the observed parameters of molecular dynamics simulation such as the number of contacts, hydrogen bonding, center-of-mass distance and van der Waals energy values confirm the encapsulation of mercaptopurine molecule inside the cucurbit[7]urils cavity at about 3.2 ns.

Molecular mechanism of transcription inhibition by phage T7 gp2 protein.

PubMed

Mekler, Vladimir; Minakhin, Leonid; Sheppard, Carol; Wigneshweraraj, Sivaramesh; Severinov, Konstantin

2011-11-11

Escherichia coli T7 bacteriophage gp2 protein is a potent inhibitor of host RNA polymerase (RNAP). gp2 inhibits formation of open promoter complex by binding to the β' jaw, an RNAP domain that interacts with downstream promoter DNA. Here, we used an engineered promoter with an optimized sequence to obtain and characterize a specific promoter complex containing RNAP and gp2. In this complex, localized melting of promoter DNA is initiated but does not propagate to include the point of the transcription start. As a result, the complex is transcriptionally inactive. Using a highly sensitive RNAP beacon assay, we performed quantitative real-time measurements of specific binding of the RNAP-gp2 complex to promoter DNA and various promoter fragments. In this way, the effect of gp2 on RNAP interaction with promoters was dissected. As expected, gp2 greatly decreased RNAP affinity to downstream promoter duplex. However, gp2 also inhibited RNAP binding to promoter fragments that lacked downstream promoter DNA that interacts with the β' jaw. The inhibition was caused by gp2-mediated decrease of the RNAP binding affinity to template and non-template strand segments of the transcription bubble downstream of the -10 promoter element. The inhibition of RNAP interactions with single-stranded segments of the transcription bubble by gp2 is a novel effect, which may occur via allosteric mechanism that is set in motion by the gp2 binding to the β' jaw. Copyright © 2011 Elsevier Ltd. All rights reserved.

Binding Site and Potency Prediction of Teixobactin and other Lipid II Ligands by Statistical Base Scoring of Conformational Space Maps.

PubMed

Lungu, Claudiu N; Diudea, Mircea V

2018-01-01

Lipid II, a peptidoglycan, is a precursor in bacterial cell synthesis. It has both hydrophilic and lipophilic properties. The molecule translocates a bacterial membrane to deliver and incorporate "building blocks" from disaccharide-pentapeptide into the peptidoglican wall. Lipid II is a valid antibiotic target. A receptor binding pocket may be occupied by a ligand in various plausible conformations, among which only few ones are energetically related to a biological activity in the physiological efficiency domain. This paper reports the mapping of the conformational space of Lipid II in its interaction with Teixobactin and other Lipid II ligands. In order to study computationally the complex between Lipid II and ligands, a docking study was first carried on. Docking site was retrieved form literature. After docking, 5 ligand conformations and further 5 complexes (denoted 00 to 04) for each molecule were taken into account. For each structure, conformational studies were performed. Statistical analysis, conformational analysis and molecular dynamics based clustering were used to predict the potency of these compounds. A score for potency prediction was developed. Appling lipid II classification according to Lipid II conformational energy, a conformation of Teixobactin proved to be energetically favorable, followed by Oritravicin, Dalbavycin, Telvanicin, Teicoplamin and Vancomycin, respectively. Scoring of molecules according to cluster band and PCA produced the same result. Molecules classified according to standard deviations showed Dalbavycin as the most favorable conformation, followed by Teicoplamin, Telvanicin, Teixobactin, Oritravicin and Vancomycin, respectively. Total score showing best energetic efficiency of complex formation shows Teixobactin to have the best conformation (a score of 15 points) followed by Dalbavycin (14 points), Oritravicin (12v points), Telvanicin (10 points), Teicoplamin (9 points), Vancomycin (3 points). Statistical analysis of conformations can be used to predict the efficiency of ligand - target interaction and consecutively to find insight regarding ligand potency and postulate about favorable conformation of ligand and binding site. In this study it was shown that Teixobactin is more efficient in binding with Lipid II compared to Vancomycin, results confirmed by experimental data reported in literature. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Interaction of dengue virus nonstructural protein 5 with Daxx modulates RANTES production

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

Khunchai, Sasiprapa; Graduate Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok; Junking, Mutita

Highlights: Black-Right-Pointing-Pointer For the first time how DENV NS5 increases RANTES production. Black-Right-Pointing-Pointer DENV NS5 physically interacts with human Daxx. Black-Right-Pointing-Pointer Nuclear localization of NS5 is required for Daxx interaction and RANTES production. -- Abstract: Dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS), caused by dengue virus (DENV) infection, are important public health problems in the tropical and subtropical regions. Abnormal hemostasis and plasma leakage are the main patho-physiological changes in DHF/DSS. A remarkably increased production of cytokines, the so called 'cytokine storm', is observed in the patients with DHF/DSS. A complex interaction between DENV proteinsmore » and the host immune response contributes to cytokine production. However, the molecular mechanism(s) by which DENV nonstructural protein 5 (NS5) mediates these responses has not been fully elucidated. In the present study, yeast two-hybrid assay was performed to identify host proteins interacting with DENV NS5 and a death-domain-associate protein (Daxx) was identified. The in vivo relevance of this interaction was suggested by co-immunoprecipitation and nuclear co-localization of these two proteins in HEK293 cells expressing DENV NS5. HEK293 cells expressing DENV NS5-K/A, which were mutated at the nuclear localization sequences (NLS), were created to assess its functional roles in nuclear translocation, Daxx interaction, and cytokine production. In the absence of NLS, DENV NS5 could neither translocate into the nucleus nor interact with Daxx to increase the DHF-associated cytokine, RANTES (CCL5) production. This work demonstrates the interaction between DENV NS5 and Daxx and the role of the interaction on the modulation of RANTES production.« less

Spectroscopic studies on the interaction of cimetidine drug with biologically significant σ- and π-acceptors

NASA Astrophysics Data System (ADS)

Pandeeswaran, M.; Elango, K. P.

2010-05-01

Spectroscopic studies revealed that the interaction of cimetidine drug with electron acceptors iodine and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) resulted through the initial formation of ionic intermediate to charge transfer (CT) complex. The CT-complexes of the interactions have been characterized using UV-vis, 1H NMR, FT-IR and GC-MS techniques. The formation of triiodide ion, I 3-, is further confirmed by the observation of the characteristic bands in the far IR spectrum for non-linear I 3- ion with C s symmetry at 156 and 131 cm -1 assigned to νas(I-I) and νs(I-I) of the I-I bond and at 73 cm -1 due to bending δ(I 3-). The rate of formation of the CT-complexes has been measured and discussed as a function of relative permittivity of solvent and temperature. The influence of relative permittivity of the medium on the rate indicated that the intermediate is more polar than the reactants and this observation was further supported by spectral studies. Based on the spectroscopic results plausible mechanisms for the interaction of the drug with the chosen acceptors were proposed and discussed and the point of attachment of the multifunctional cimetidine drug with these acceptors during the formation of CT-complex has been established.

­Understanding Information Flow Interaction along Separable Causal Paths in Environmental Signals

NASA Astrophysics Data System (ADS)

Jiang, P.; Kumar, P.

2017-12-01

Multivariate environmental signals reflect the outcome of complex inter-dependencies, such as those in ecohydrologic systems. Transfer entropy and information partitioning approaches have been used to characterize such dependencies. However, these approaches capture net information flow occurring through a multitude of pathways involved in the interaction and as a result mask our ability to discern the causal interaction within an interested subsystem through specific pathways. We build on recent developments of momentary information transfer along causal paths proposed by Runge [2015] to develop a framework for quantifying information decomposition along separable causal paths. Momentary information transfer along causal paths captures the amount of information flow between any two variables lagged at two specific points in time. Our approach expands this concept to characterize the causal interaction in terms of synergistic, unique and redundant information flow through separable causal paths. Multivariate analysis using this novel approach reveals precise understanding of causality and feedback. We illustrate our approach with synthetic and observed time series data. We believe the proposed framework helps better delineate the internal structure of complex systems in geoscience where huge amounts of observational datasets exist, and it will also help the modeling community by providing a new way to look at the complexity of real and modeled systems. Runge, Jakob. "Quantifying information transfer and mediation along causal pathways in complex systems." Physical Review E 92.6 (2015): 062829.

THz frequency spectrum of protein-solvent interaction energy using a recurrence plot-based Wiener-Khinchin method.

PubMed

Karain, Wael

2016-10-01

The dynamics of a protein and the water surrounding it are coupled via nonbonded energy interactions. This coupling can exhibit a complex, nonlinear, and nonstationary nature. The THz frequency spectrum for this interaction energy characterizes both the vibration spectrum of the water hydrogen bond network, and the frequency range of large amplitude modes of proteins. We use a Recurrence Plot based Wiener-Khinchin method RPWK to calculate this spectrum, and the results are compared to those determined using the classical auto-covariance-based Wiener-Khinchin method WK. The frequency spectra for the total nonbonded interaction energy extracted from molecular dynamics simulations between the β-Lactamase Inhibitory Protein BLIP, and water molecules within a 10 Å distance from the protein surface, are calculated at 150, 200, 250, and 310 K, respectively. Similar calculations are also performed for the nonbonded interaction energy between the residues 49ASP, 53TYR, and 142PHE in BLIP, with water molecules within 10 Å from each residue respectively at 150, 200, 250, and 310 K. A comparison of the results shows that RPWK performs better than WK, and is able to detect some frequency data points that WK fails to detect. This points to the importance of using methods capable of taking the complex nature of the protein-solvent energy landscape into consideration, and not to rely on standard linear methods. In general, RPWK can be a valuable addition to the analysis tools for protein molecular dynamics simulations. Proteins 2016; 84:1549-1557. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Lanthanide-organic complexes based on polyoxometalates: Solvent effect on the luminescence properties

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

Tang Qun; Liu Shuxia, E-mail: liusx@nenu.edu.cn; Liang Dadong

2012-06-15

A series of lanthanide-organic complexes based on polyoxometalates (POMs) [Ln{sub 2}(DNBA){sub 4}(DMF){sub 8}][W{sub 6}O{sub 19}] (Ln=La(1), Ce(2), Sm(3), Eu(4), Gd(5); DNBA=3,5-dinitrobenzoate; DMF=N,N-dimethylformamide) has been synthesized. These complexes consist of [W{sub 6}O{sub 19}]{sup 2-} and dimeric [Ln{sub 2}(DNBA){sub 4}(DMF){sub 8}]{sup 2+} cations. The luminescence properties of 4 are measured in solid state and different solutions, respectively. Notably, the emission intensity increases gradually with the increase of solvent permittivity, and this solvent effect can be directly observed by electrospray mass spectrometry (ESI-MS). The analyses of ESI-MS show that the eight coordinated solvent DMF units of dimeric cation are active. They can movemore » away from dimeric cations and exchange with solvent molecules. Although the POM anions escape from 3D supramolecular network, the dimeric state structure of [Ln{sub 2}(DNBA){sub 4}]{sup 2+} remains unchanged in solution. The conservation of red luminescence is attributed to the maintenance of the aggregated state structures of dimeric cations. - Graphical abstract: 3D POMs-based lanthanide-organic complexes performed the solvent effect on the luminescence property. The origin of such solvent effect can be understood and explained on the basis of the existence of coordinated active sites by the studies of ESI-MS. Highlights: Black-Right-Pointing-Pointer The solvent effect on the luminescence property of POMs-based lanthanide-organic complexes. Black-Right-Pointing-Pointer ESI-MS analyses illuminate the correlation between the structure and luminescence property. Black-Right-Pointing-Pointer The dimeric cations have eight active sites of solvent coordination. Black-Right-Pointing-Pointer The aggregated state structure of dimer cation remains unchanged in solution. Black-Right-Pointing-Pointer Luminescence associating with ESI-MS is a new method for investigating the interaction of complex and solvent.« less

Type-III and IV interacting Weyl points

NASA Astrophysics Data System (ADS)

Nissinen, J.; Volovik, G. E.

2017-04-01

3+1-dimensional Weyl fermions in interacting systems are described by effective quasi-relativistic Green's functions parametrized by a 16-element matrix e α μ in an expansion around the Weyl point. The matrix e α μ can be naturally identified as an effective tetrad field for the fermions. The correspondence between the tetrad field and an effective quasi-relativistic metric gμν governing the Weyl fermions allows for the possibility to simulate different classes of metric fields emerging in general relativity in interacting Weyl semimetals. According to this correspondence, there can be four types of Weyl fermions, depending on the signs of the components g 00 and g 00 of the effective metric. In addition to the conventional type-I fermions with a tilted Weyl cone and type-II fermions with an overtilted Weyl cone for g 00 > 0 and, respectively, g 00 > 0 or g 00 < 0, we find additional "type-III" and "type-IV" Weyl fermions with instabilities (complex frequencies) for g 00 < 0 and g 00 > 0 or g 00 < 0, respectively. While the type-I and type-II Weyl points allow us to simulate the black hole event horizon at an interface where g 00 changes sign, the type-III Weyl point leads to effective spacetimes with closed timelike curves.

Enhanced cryopreservation of MSCs in microfluidic bioreactor by regulated shear flow

PubMed Central

Bissoyi, Akalabya; Bit, Arindam; Singh, Bikesh Kumar; Singh, Abhishek Kumar; Patra, Pradeep Kumar

2016-01-01

Cell-matrix systems can be stored for longer period of time by means of cryopreservation. Cell-matrix and cell-cell interaction has been found to be critical in a number of basic biological processes. Tissue structure maintenance, cell secretary activity, cellular migration, and cell-cell communication all exist because of the presence of cell interactions. This complex and co-ordinated interaction between cellular constituents, extracellular matrix and adjacent cells has been identified as a significant contributor in the overall co-ordination of tissue. The prime objective of this investigation is to evaluate the effects of shear-stress and cell-substrate interaction in successful recovery of adherent human mesenchymal-stem-cells (hMSCs). A customized microfluidic bioreactor has been used for the purpose. We have measured the changes in focal-point-adhesion (FPAs) by changing induced shear stress inside the bioreactor. The findings indicate that with increase in shear stress, FPAs increases between substrate and MSCs. Further, experimental results show that increased FPAs (4e-3 μbar) enhances the cellular survivability of adherent MSCs. Probably, for the first time involvement of focal point interaction in the outcome of cryopreservation of MSCs has been clarified, and it proved a potentially new approach for modification of cryopreservation protocol by up-regulating focal point of cells to improve its clinical application. PMID:27748463

Information entropy to measure the spatial and temporal complexity of solute transport in heterogeneous porous media

NASA Astrophysics Data System (ADS)

Li, Weiyao; Huang, Guanhua; Xiong, Yunwu

2016-04-01

The complexity of the spatial structure of porous media, randomness of groundwater recharge and discharge (rainfall, runoff, etc.) has led to groundwater movement complexity, physical and chemical interaction between groundwater and porous media cause solute transport in the medium more complicated. An appropriate method to describe the complexity of features is essential when study on solute transport and conversion in porous media. Information entropy could measure uncertainty and disorder, therefore we attempted to investigate complexity, explore the contact between the information entropy and complexity of solute transport in heterogeneous porous media using information entropy theory. Based on Markov theory, two-dimensional stochastic field of hydraulic conductivity (K) was generated by transition probability. Flow and solute transport model were established under four conditions (instantaneous point source, continuous point source, instantaneous line source and continuous line source). The spatial and temporal complexity of solute transport process was characterized and evaluated using spatial moment and information entropy. Results indicated that the entropy increased as the increase of complexity of solute transport process. For the point source, the one-dimensional entropy of solute concentration increased at first and then decreased along X and Y directions. As time increased, entropy peak value basically unchanged, peak position migrated along the flow direction (X direction) and approximately coincided with the centroid position. With the increase of time, spatial variability and complexity of solute concentration increase, which result in the increases of the second-order spatial moment and the two-dimensional entropy. Information entropy of line source was higher than point source. Solute entropy obtained from continuous input was higher than instantaneous input. Due to the increase of average length of lithoface, media continuity increased, flow and solute transport complexity weakened, and the corresponding information entropy also decreased. Longitudinal macro dispersivity declined slightly at early time then rose. Solute spatial and temporal distribution had significant impacts on the information entropy. Information entropy could reflect the change of solute distribution. Information entropy appears a tool to characterize the spatial and temporal complexity of solute migration and provides a reference for future research.

Laser desorption single-conformation UV and IR spectroscopy of the sulfonamide drug sulfanilamide, the sulfanilamide-water complex, and the sulfanilamide dimer.

PubMed

Uhlemann, Thomas; Seidel, Sebastian; Müller, Christian W

2017-06-07

We have studied the conformational preferences of the sulfonamide drug sulfanilamide, its dimer, and its monohydrated complex through laser desorption single-conformation UV and IR spectroscopy in a molecular beam. Based on potential energy curves for the inversion of the anilinic and the sulfonamide NH 2 groups calculated at DFT level, we suggest that the zero-point level wave function of the sulfanilamide monomer is appreciably delocalized over all four conformer wells. The sulfanilamide dimer, and the monohydrated complex each exhibit a single isomer in the molecular beam. The isomeric structures of the sulfanilamide dimer and the monohydrated sulfanilamide complex were assigned based on their conformer-specific IR spectra in the NH and OH stretch region. Quantum Theory of Atoms in Molecules (QTAIM) analysis of the calculated electron density in the water complex suggests that the water molecule is bound side-on in a hydrogen bonding pocket, donating one O-HO[double bond, length as m-dash]S hydrogen bond and accepting two hydrogen bonds, a NHO and a CHO hydrogen bond. QTAIM analysis of the dimer electron density suggests that the C i symmetry dimer structure exhibits two dominating N-HO[double bond, length as m-dash]S hydrogen bonds, and three weaker types of interactions: two CHO bonds, two CHN bonds, and a chalcogen OO interaction. Most interestingly, the molecular beam dimer structure closely resembles the R dimer unit - the dimer unit with the greatest interaction energy - of the α, γ, and δ crystal polymorphs. Interacting Quantum Atoms analysis provides evidence that the total intermolecular interaction in the dimer is dominated by the short-range exchange-correlation contribution.

Linear control theory for gene network modeling.

PubMed

Shin, Yong-Jun; Bleris, Leonidas

2010-09-16

Systems biology is an interdisciplinary field that aims at understanding complex interactions in cells. Here we demonstrate that linear control theory can provide valuable insight and practical tools for the characterization of complex biological networks. We provide the foundation for such analyses through the study of several case studies including cascade and parallel forms, feedback and feedforward loops. We reproduce experimental results and provide rational analysis of the observed behavior. We demonstrate that methods such as the transfer function (frequency domain) and linear state-space (time domain) can be used to predict reliably the properties and transient behavior of complex network topologies and point to specific design strategies for synthetic networks.

How social factors and behavioural strategies affect feeding and social interaction patterns in pigs.

PubMed

Boumans, Iris J M M; de Boer, Imke J M; Hofstede, Gert Jan; Bokkers, Eddie A M

2018-04-26

Animals living in groups compete for food resources and face food conflicts. These conflicts are affected by social factors (e.g. competition level) and behavioural strategies (e.g. avoidance). This study aimed to deepen our understanding of the complex interactions between social factors and behavioural strategies affecting feeding and social interaction patterns in animals. We focused on group-housed growing pigs, Sus scrofa, which typically face conflicts around the feeder, and of which patterns in various competitive environments (i.e. pig:feeder ratio) have been documented soundly. An agent-based model was developed to explore how interactions among social factors and behavioural strategies can affect various feeding and social interaction patterns differently under competitive situations. Model results show that pig and diet characteristics interact with group size and affect daily feeding patterns (e.g. feed intake and feeding time) and conflicts around the feeder. The level of competition can cause a turning point in feeding and social interaction patterns. Beyond a certain point of competition, meal-based (e.g. meal frequency) and social interaction patterns (e.g. displacements) are determined mainly by behavioural strategies. The average daily feeding time can be used to predict the group size at which this turning point occurs. Under the model's assumptions, social facilitation was relatively unimportant in the causation of behavioural patterns in pigs. To validate our model, simulated patterns were compared with empirical patterns in conventionally housed pigs. Similarities between empirical and model patterns support the model results. Our model can be used as a tool in further research for studying the effects of social factors and group dynamics on individual variation in feeding and social interaction patterns in pigs, as well as in other animal species. Copyright © 2018 Elsevier Inc. All rights reserved.

Humic acid protein complexation

NASA Astrophysics Data System (ADS)

Tan, W. F.; Koopal, L. K.; Weng, L. P.; van Riemsdijk, W. H.; Norde, W.

2008-04-01

Interactions of purified Aldrich humic acid (PAHA) with lysozyme (LSZ) are investigated. In solution LSZ is moderately positively and PAHA negatively charged at the investigated pH values. The proton binding of PAHA and of LSZ is determined by potentiometric proton titrations at various KCl concentrations. It is also measured for two mixtures of PAHA-LSZ and compared with theoretically calculated proton binding assuming no mutual interaction. The charge adaptation due to PAHA-LSZ interaction is relatively small and only significant at low and high pH. Next to the proton binding, the mass ratio PAHA/LSZ at the iso-electric point (IEP) of the complex at given solution conditions is measured together with the pH using the Mütek particle charge detector. From the pH changes the charge adaptation due to the interaction can be found. Also these measurements show that the net charge adaptation is weak for PAHA-LSZ complexes at their IEP. PAHA/LSZ mass ratios in the complexes at the IEP are measured at pH 5 and 7. At pH 5 and 50 mmol/L KCl the charge of the complex is compensated for 30-40% by K +; at pH 7, where LSZ has a rather low positive charge, this is 45-55%. At pH 5 and 5 mmol/L KCl the PAHA/LSZ mass ratio at the IEP of the complex depends on the order of addition. When LSZ is added to PAHA about 25% K + is included in the complex, but no K + is incorporated when PAHA is added to LSZ. The flocculation behavior of the complexes is also different. After LSZ addition to PAHA slow precipitation occurs (6-24 h) in the IEP, but after addition of PAHA to LSZ no precipitation can be seen after 12 h. Clearly, PAHA/LSZ complexation and the colloidal stability of PAHA-LSZ aggregates depend on the order of addition. Some implications of the observed behavior are discussed.

Direct interaction between the tobacco mosaic virus helicase domain and the ATP-bound resistance protein, N factor during the hypersensitive response in tobacco plants.

PubMed

Ueda, Hirokazu; Yamaguchi, Yube; Sano, Hiroshi

2006-05-01

Plants cope with pathogens with distinct mechanisms. One example is a gene-for-gene system, in which plants recognize the pathogen molecule by specified protein(s), this being called the R factor. However, mechanisms of interaction between proteins from the host and the pathogen are not completely understood. Here, we analyzed the mode of interaction between the N factor, a tobacco R factor, and the helicase domain (p50) of tobacco mosaic virus (TMV). To this end, domain dissected proteins were prepared and subjected to Agroinfiltration into intact leaves, followed by yeast two hybrid and pull-down assays. The results pointed to three novel features. First, the N factor was found to directly bind to the p50 of TMV, second, ATP was pre-requisite for this interaction, with formation of an ATP/N factor complex, and third, the N factor was shown to possess ATPase activity, which is enhanced by the p50. Moreover, we found that intra- and/or inter-molecular interactions take place in the N factor molecule. This interaction required ATP, and was disrupted by the p50. Based on these results, we propose a following model for the TMV recognition mechanism in tobacco plants. The N factor forms a complex with ATP, to which the helicase domain interacts, and enhances ATP hydrolysis. The resulting ADP/N factor complex then changes its conformation, thereby facilitating further interaction with the down-stream signaling factor(s). This model is consistent with the idea of 'protein machine'.

RNA sequencing of contaminated seeds reveals the state of the seed permissive for pre-harvest aflatoxin contamination and points to a potential susceptibility factor

USDA-ARS?s Scientific Manuscript database

Pre-harvest aflatoxin contamination (PAC) is a major problem facing peanut production worldwide. Produced by the ubiquitous soil fungus, Aspergillus flavus, aflatoxin is the most potent naturally occurring known carcinogen. The interaction between fungus and host resulting in PAC is complex, and b...

Numerical simulation of magnetic interactions in polycrystalline YFeO 3

NASA Astrophysics Data System (ADS)

Lima, E.; Martins, T. B.; Rechenberg, H. R.; Goya, G. F.; Cavelius, C.; Rapalaviciute, R.; Hao, S.; Mathur, S.

The magnetic behavior of polycrystalline yttrium orthoferrite was studied from the experimental and theoretical points of view. Magnetization measurements up to 170 kOe were carried out on a single-phase YFeO 3 sample synthesized from heterobimetallic alkoxides. The complex interplay between weak-ferromagnetic and antiferromagnetic interactions, observed in the experimental M( H) curves, was successfully simulated by locally minimizing the magnetic energy of two interacting Fe sublattices. The resulting values of exchange field ( HE=5590 kOe), anisotropy field ( HA=0.5 kOe) and Dzyaloshinsky-Moriya antisymmetric field ( HD=149 kOe) are in good agreement with previous reports on this system.

Information for Successful Interaction with Autonomous Systems

NASA Technical Reports Server (NTRS)

Malin, Jane T.; Johnson, Kathy A.

2003-01-01

Interaction in heterogeneous mission operations teams is not well matched to classical models of coordination with autonomous systems. We describe methods of loose coordination and information management in mission operations. We describe an information agent and information management tool suite for managing information from many sources, including autonomous agents. We present an integrated model of levels of complexity of agent and human behavior, which shows types of information processing and points of potential error in agent activities. We discuss the types of information needed for diagnosing problems and planning interactions with an autonomous system. We discuss types of coordination for which designs are needed for autonomous system functions.

The Voronoi Implicit Interface Method for computing multiphase physics

PubMed Central

Saye, Robert I.; Sethian, James A.

2011-01-01

We introduce a numerical framework, the Voronoi Implicit Interface Method for tracking multiple interacting and evolving regions (phases) whose motion is determined by complex physics (fluids, mechanics, elasticity, etc.), intricate jump conditions, internal constraints, and boundary conditions. The method works in two and three dimensions, handles tens of thousands of interfaces and separate phases, and easily and automatically handles multiple junctions, triple points, and quadruple points in two dimensions, as well as triple lines, etc., in higher dimensions. Topological changes occur naturally, with no surgery required. The method is first-order accurate at junction points/lines, and of arbitrarily high-order accuracy away from such degeneracies. The method uses a single function to describe all phases simultaneously, represented on a fixed Eulerian mesh. We test the method’s accuracy through convergence tests, and demonstrate its applications to geometric flows, accurate prediction of von Neumann’s law for multiphase curvature flow, and robustness under complex fluid flow with surface tension and large shearing forces. PMID:22106269

The Voronoi Implicit Interface Method for computing multiphase physics.

PubMed

Saye, Robert I; Sethian, James A

2011-12-06

We introduce a numerical framework, the Voronoi Implicit Interface Method for tracking multiple interacting and evolving regions (phases) whose motion is determined by complex physics (fluids, mechanics, elasticity, etc.), intricate jump conditions, internal constraints, and boundary conditions. The method works in two and three dimensions, handles tens of thousands of interfaces and separate phases, and easily and automatically handles multiple junctions, triple points, and quadruple points in two dimensions, as well as triple lines, etc., in higher dimensions. Topological changes occur naturally, with no surgery required. The method is first-order accurate at junction points/lines, and of arbitrarily high-order accuracy away from such degeneracies. The method uses a single function to describe all phases simultaneously, represented on a fixed Eulerian mesh. We test the method's accuracy through convergence tests, and demonstrate its applications to geometric flows, accurate prediction of von Neumann's law for multiphase curvature flow, and robustness under complex fluid flow with surface tension and large shearing forces.

The Voronoi Implicit Interface Method for computing multiphase physics

DOE PAGES

Saye, Robert I.; Sethian, James A.

2011-11-21

In this paper, we introduce a numerical framework, the Voronoi Implicit Interface Method for tracking multiple interacting and evolving regions (phases) whose motion is determined by complex physics (fluids, mechanics, elasticity, etc.), intricate jump conditions, internal constraints, and boundary conditions. The method works in two and three dimensions, handles tens of thousands of interfaces and separate phases, and easily and automatically handles multiple junctions, triple points, and quadruple points in two dimensions, as well as triple lines, etc., in higher dimensions. Topological changes occur naturally, with no surgery required. The method is first-order accurate at junction points/lines, and of arbitrarilymore » high-order accuracy away from such degeneracies. The method uses a single function to describe all phases simultaneously, represented on a fixed Eulerian mesh. Finally, we test the method’s accuracy through convergence tests, and demonstrate its applications to geometric flows, accurate prediction of von Neumann’s law for multiphase curvature flow, and robustness under complex fluid flow with surface tension and large shearing forces.« less

Understanding protein-nanoparticle interaction: a new gateway to disease therapeutics.

PubMed

Giri, Karuna; Shameer, Khader; Zimmermann, Michael T; Saha, Sounik; Chakraborty, Prabir K; Sharma, Anirudh; Arvizo, Rochelle R; Madden, Benjamin J; Mccormick, Daniel J; Kocher, Jean-Pierre A; Bhattacharya, Resham; Mukherjee, Priyabrata

2014-06-18

Molecular identification of protein molecules surrounding nanoparticles (NPs) may provide useful information that influences NP clearance, biodistribution, and toxicity. Hence, nanoproteomics provides specific information about the environment that NPs interact with and can therefore report on the changes in protein distribution that occurs during tumorigenesis. Therefore, we hypothesized that characterization and identification of protein molecules that interact with 20 nm AuNPs from cancer and noncancer cells may provide mechanistic insights into the biology of tumor growth and metastasis and identify new therapeutic targets in ovarian cancer. Hence, in the present study, we systematically examined the interaction of the protein molecules with 20 nm AuNPs from cancer and noncancerous cell lysates. Time-resolved proteomic profiles of NP-protein complexes demonstrated electrostatic interaction to be the governing factor in the initial time-points which are dominated by further stabilization interaction at longer time-points as determined by ultraviolet-visible spectroscopy (UV-vis), dynamic light scattering (DLS), ζ-potential measurements, transmission electron microscopy (TEM), and tandem mass spectrometry (MS/MS). Reduction in size, charge, and number of bound proteins were observed as the protein-NP complex stabilized over time. Interestingly, proteins related to mRNA processing were overwhelmingly represented on the NP-protein complex at all times. More importantly, comparative proteomic analyses revealed enrichment of a number of cancer-specific proteins on the AuNP surface. Network analyses of these proteins highlighted important hub nodes that could potentially be targeted for maximal therapeutic advantage in the treatment of ovarian cancer. The importance of this methodology and the biological significance of the network proteins were validated by a functional study of three hubs that exhibited variable connectivity, namely, PPA1, SMNDC1, and PI15. Western blot analysis revealed overexpression of these proteins in ovarian cancer cells when compared to normal cells. Silencing of PPA1, SMNDC1, and PI15 by the siRNA approach significantly inhibited proliferation of ovarian cancer cells and the effect correlated with the connectivity pattern obtained from our network analyses.

Epigenetic involvement of Alien/ESET complex in thyroid hormone-mediated repression of E2F1 gene expression and cell proliferation

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

Hong, Wei, E-mail: hongwei@tijmu.edu.cn; College of Basic Medicine, Tianjin Medical University, 300070 Tianjin; Li, Jinru

Highlights: Black-Right-Pointing-Pointer Corepressor Alien interacts with histone methyltransferase ESET in vivo. Black-Right-Pointing-Pointer Alien/ESET complex is recruited to nTRE of T3-responsive gene by liganded TR{beta}1. Black-Right-Pointing-Pointer ESET-mediated H3K9 methylation is required for liganded TR{beta}1-repressed transcription. Black-Right-Pointing-Pointer ESET is involved in T3-repressed G1/S phase transition and proliferation. -- Abstract: The ligand-bound thyroid hormone receptor (TR) is known to repress via a negative TRE (nTRE) the expression of E2F1, a key transcription factor that controls the G1/S phase transition. Alien has been identified as a novel interacting factor of E2F1 and acts as a corepressor of E2F1. The detailed molecular mechanism by whichmore » Alien inhibits E2F1 gene expression remains unclear. Here, we report that the histone H3 lysine 9 (H3K9) methyltransferase (HMT) ESET is an integral component of the corepressor Alien complex and the Alien/ESET complex is recruited to both sites, the E2F1 and the nTRE site of the E2F1 gene while the recruitment to the negative thyroid hormone response element (nTRE) is induced by the ligand-bound TR{beta}1 within the E2F1 gene promoter. We show that, overexpression of ESET promotes, whereas knockdown of ESET releases, the inhibition of TR{beta}1-regulated gene transcription upon T3 stimulation; and H3K9 methylation is required for TR{beta}1-repressed transcription. Furthermore, depletion of ESET impairs thyroid hormone-repressed proliferation as well as the G1/S transition of the cell cycle. Taken together, our data indicate that ESET is involved in TR{beta}1-mediated transcription repression and provide a molecular basis of thyroid hormone-induced repression of proliferation.« less

Network succession reveals the importance of competition in response to emulsified vegetable oil amendment for uranium bioremediation.

PubMed

Deng, Ye; Zhang, Ping; Qin, Yujia; Tu, Qichao; Yang, Yunfeng; He, Zhili; Schadt, Christopher Warren; Zhou, Jizhong

2016-01-01

Discerning network interactions among different species/populations in microbial communities has evoked substantial interests in recent years, but little information is available about temporal dynamics of microbial network interactions in response to environmental perturbations. Here, we modified the random matrix theory-based network approach to discern network succession in groundwater microbial communities in response to emulsified vegetable oil (EVO) amendment for uranium bioremediation. Groundwater microbial communities from one control and seven monitor wells were analysed with a functional gene array (GeoChip 3.0), and functional molecular ecological networks (fMENs) at different time points were reconstructed. Our results showed that the network interactions were dramatically altered by EVO amendment. Dynamic and resilient succession was evident: fairly simple at the initial stage (Day 0), increasingly complex at the middle period (Days 4, 17, 31), most complex at Day 80, and then decreasingly complex at a later stage (140-269 days). Unlike previous studies in other habitats, negative interactions predominated in a time-series fMEN, suggesting strong competition among different microbial species in the groundwater systems after EVO injection. Particularly, several keystone sulfate-reducing bacteria showed strong negative interactions with their network neighbours. These results provide mechanistic understanding of the decreased phylogenetic diversity during environmental perturbations. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Network succession reveals the importance of competition in response to emulsified vegetable oil amendment for uranium bioremediation: Competition in bioremediation system

DOE PAGES

Deng, Ye; Zhang, Ping; Qin, Yujia; ...

2015-08-11

When trying to discern network interactions among different species/populations in microbial communities interests have been evoked in recent years, but little information is available about temporal dynamics of microbial network interactions in response to environmental perturbations. We modified the random matrix theory-based network approach to discern network succession in groundwater microbial communities in response to emulsified vegetable oil (EVO) amendment for uranium bioremediation. Groundwater microbial communities from one control and seven monitor wells were analysed with a functional gene array (GeoChip 3.0), and functional molecular ecological networks (fMENs) at different time points were reconstructed. Our results showed that the networkmore » interactions were dramatically altered by EVO amendment. Dynamic and resilient succession was evident: fairly simple at the initial stage (Day 0), increasingly complex at the middle period (Days 4, 17, 31), most complex at Day 80, and then decreasingly complex at a later stage (140–269 days). Unlike previous studies in other habitats, negative interactions predominated in a time-series fMEN, suggesting strong competition among different microbial species in the groundwater systems after EVO injection. In particular, several keystone sulfate-reducing bacteria showed strong negative interactions with their network neighbours. These results provide mechanistic understanding of the decreased phylogenetic diversity during environmental perturbations.« less

Proteomic identification of dysferlin-interacting protein complexes in human vascular endothelium

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

Leung, Cleo; Utokaparch, Soraya; Sharma, Arpeeta

2011-11-18

Highlights: Black-Right-Pointing-Pointer Bi-directional (inward and outward) movement of GFP-dysferlin in COS-7 cells. Black-Right-Pointing-Pointer Dysferlin interacts with key signaling proteins for transcytosis in EC. Black-Right-Pointing-Pointer Dysferlin mediates trafficking of vesicles carrying protein cargos in EC. -- Abstract: Dysferlin is a membrane-anchored protein known to facilitate membrane repair in skeletal muscles following mechanical injury. Mutations of dysferlin gene impair sarcolemma integrity, a hallmark of certain forms of muscular dystrophy in patients. Dysferlin contains seven calcium-dependent C2 binding domains, which are required to promote fusion of intracellular membrane vesicles. Emerging evidence reveal the unexpected expression of dysferlin in non-muscle, non-mechanically active tissues, suchmore » as endothelial cells, which cast doubts over the belief that ferlin proteins act exclusively as membrane repair proteins. We and others have shown that deficient trafficking of membrane bound proteins in dysferlin-deficient cells, suggesting that dysferlin might mediate trafficking of client proteins. Herein, we describe the intracellular trafficking and movement of GFP-dysferlin positive vesicles in unfixed reconstituted cells using live microscopy. By performing GST pull-down assays followed by mass spectrometry, we identified dysferlin binding protein complexes in human vascular endothelial cells. Together, our data further support the claims that dysferlin not only mediates membrane repair but also trafficking of client proteins, ultimately, help bridging dysferlinopathies to aberrant membrane signaling.« less

Adsorption of bovine serum albumin on silicon dioxide nanoparticles: Impact of pH on nanoparticle-protein interactions.

PubMed

Givens, Brittany E; Diklich, Nina D; Fiegel, Jennifer; Grassian, Vicki H

2017-05-03

Bovine serum albumin (BSA) adsorbed on amorphous silicon dioxide (SiO 2 ) nanoparticles was studied as a function of pH across the range of 2 to 8. Aggregation, surface charge, surface coverage, and protein structure were investigated over this entire pH range. SiO 2 nanoparticle aggregation is found to depend upon pH and differs in the presence of adsorbed BSA. For SiO 2 nanoparticles truncated with hydroxyl groups, the largest aggregates were observed at pH 3, close to the isoelectric point of SiO 2 nanoparticles, whereas for SiO 2 nanoparticles with adsorbed BSA, the aggregate size was the greatest at pH 3.7, close to the isoelectric point of the BSA-SiO 2 complex. Surface coverage of BSA was also the greatest at the isoelectric point of the BSA-SiO 2 complex with a value of ca. 3 ±   1 × 10 11 molecules cm -2 . Furthermore, the secondary protein structure was modified when compared to the solution phase at all pH values, but the most significant differences were seen at pH 7.4 and below. It is concluded that protein-nanoparticle interactions vary with solution pH, which may have implications for nanoparticles in different biological fluids (e.g., blood, stomach, and lungs).

Versatility and Invariance in the Evolution of Homologous Heteromeric Interfaces

PubMed Central

Andreani, Jessica; Faure, Guilhem; Guerois, Raphaël

2012-01-01

Evolutionary pressures act on protein complex interfaces so that they preserve their complementarity. Nonetheless, the elementary interactions which compose the interface are highly versatile throughout evolution. Understanding and characterizing interface plasticity across evolution is a fundamental issue which could provide new insights into protein-protein interaction prediction. Using a database of 1,024 couples of close and remote heteromeric structural interologs, we studied protein-protein interactions from a structural and evolutionary point of view. We systematically and quantitatively analyzed the conservation of different types of interface contacts. Our study highlights astonishing plasticity regarding polar contacts at complex interfaces. It also reveals that up to a quarter of the residues switch out of the interface when comparing two homologous complexes. Despite such versatility, we identify two important interface descriptors which correlate with an increased conservation in the evolution of interfaces: apolar patches and contacts surrounding anchor residues. These observations hold true even when restricting the dataset to transiently formed complexes. We show that a combination of six features related either to sequence or to geometric properties of interfaces can be used to rank positions likely to share similar contacts between two interologs. Altogether, our analysis provides important tracks for extracting meaningful information from multiple sequence alignments of conserved binding partners and for discriminating near-native interfaces using evolutionary information. PMID:22952442

Periodontal and inflammatory bowel diseases: Is there evidence of complex pathogenic interactions?

PubMed Central

Lira-Junior, Ronaldo; Figueredo, Carlos Marcelo

2016-01-01

Periodontal disease and inflammatory bowel disease (IBD) are both chronic inflammatory diseases. Their pathogenesis is mediated by a complex interplay between a dysbiotic microbiota and the host immune-inflammatory response, and both are influenced by genetic and environmental factors. This review aimed to provide an overview of the evidence dealing with a possible pathogenic interaction between periodontal disease and IBD. There seems to be an increased prevalence of periodontal disease in patients with IBD when compared to healthy controls, probably due to changes in the oral microbiota and a higher inflammatory response. Moreover, the induction of periodontitis seems to result in gut dysbiosis and altered gut epithelial cell barrier function, which might contribute to the pathogenesis of IBD. Considering the complexity of both periodontal disease and IBD, it is very challenging to understand the possible pathways involved in their coexistence. In conclusion, this review points to a complex pathogenic interaction between periodontal disease and IBD, in which one disease might alter the composition of the microbiota and increase the inflammatory response related to the other. However, we still need more data derived from human studies to confirm results from murine models. Thus, mechanistic studies are definitely warranted to clarify this possible bidirectional association. PMID:27672291

Destabilization of the PCNA trimer mediated by its interaction with the NEIL1 DNA glycosylase

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

Prakash, Aishwarya; Moharana, Kedar; Wallace, Susan S.

The base excision repair (BER) pathway repairs oxidized lesions in the DNA that result from reactive oxygen species generated in cells. If left unrepaired, these damaged DNA bases can disrupt cellular processes such as replication. NEIL1 is one of the 11 human DNA glycosylases that catalyze the first step of the BER pathway, i.e. recognition and excision of DNA lesions. NEIL1 interacts with essential replication proteins such as the ring-shaped homotrimeric proliferating cellular nuclear antigen (PCNA). We isolated a complex formed between NEIL1 and PCNA (±DNA) using size exclusion chromatography (SEC). This interaction was confirmed using native gel electrophoresis andmore » mass spectrometry. Stokes radii measured by SEC hinted that PCNA in complex with NEIL1 (±DNA) was no longer a trimer. Height measurements and images obtained by atomic force microscopy also demonstrated the dissociation of the PCNA homotrimer in the presence of NEIL1 and DNA, while small-angle X-ray scattering analysis confirmed the NEIL1 mediated PCNA trimer dissociation and formation of a 1:1:1 NEIL1-DNA-PCNA(monomer) complex. Furthermore, ab initio shape reconstruction provides insights into the solution structure of this previously unreported complex. Together, these data point to a potential mechanistic switch between replication and BER.« less

A combined molecular dynamics simulation and quantum mechanics study on mercaptopurine interaction with the cucurbit [6,7] urils: Analysis of electronic structure.

PubMed

Zaboli, Maryam; Raissi, Heidar

2018-01-05

In the current study, the probability of complex formation between mercaptopurine drug with cucurbit[6]urils and cucurbit[7]urils has been investigated. The calculations for geometry optimization of complexes have been carried out by means of DFT (B3LYP), DFT-D (B3LYP-D) and M06-2X methods. The Atoms In Molecules (AIM), Natural Bond Orbital (NBO), NMR, the density of states (DOSs) and frontier molecular orbital (MO) analyses have been done on the inclusion complexes. In addition, the UV-Vis spectra of the first eight states have been obtained by CAM-B3LYP/TD-DFT calculation. The obtained results of the complexation process reveal that CB[7]-DRG complexes are more favorable than that of CB[6]-DRG interactions. Furthermore, our theoretical results show that configurations III and I are the most stable configurations related to the CB[6]/DRG and CB[7]/DRG interactions, respectively. The positive ∇ 2 ρ (r) and HC values at the bond critical points indicate that exist the weak H-bonds between CB[6] and CB[7] with H atoms of the drug molecule. The obtained negative binding energy values of CB[7]-DRG interaction in solution phase show the stability of these complexes in the aqueous medium. Also, all of the observed parameters of molecular dynamics simulation such as the number of contacts, hydrogen bonding, center-of-mass distance and van der Waals energy values confirm the encapsulation of mercaptopurine molecule inside the cucurbit[7]urils cavity at about 3.2ns. Copyright © 2017 Elsevier B.V. All rights reserved.

Structural symmetry and protein function.

PubMed

Goodsell, D S; Olson, A J

2000-01-01

The majority of soluble and membrane-bound proteins in modern cells are symmetrical oligomeric complexes with two or more subunits. The evolutionary selection of symmetrical oligomeric complexes is driven by functional, genetic, and physicochemical needs. Large proteins are selected for specific morphological functions, such as formation of rings, containers, and filaments, and for cooperative functions, such as allosteric regulation and multivalent binding. Large proteins are also more stable against denaturation and have a reduced surface area exposed to solvent when compared with many individual, smaller proteins. Large proteins are constructed as oligomers for reasons of error control in synthesis, coding efficiency, and regulation of assembly. Symmetrical oligomers are favored because of stability and finite control of assembly. Several functions limit symmetry, such as interaction with DNA or membranes, and directional motion. Symmetry is broken or modified in many forms: quasisymmetry, in which identical subunits adopt similar but different conformations; pleomorphism, in which identical subunits form different complexes; pseudosymmetry, in which different molecules form approximately symmetrical complexes; and symmetry mismatch, in which oligomers of different symmetries interact along their respective symmetry axes. Asymmetry is also observed at several levels. Nearly all complexes show local asymmetry at the level of side chain conformation. Several complexes have reciprocating mechanisms in which the complex is asymmetric, but, over time, all subunits cycle through the same set of conformations. Global asymmetry is only rarely observed. Evolution of oligomeric complexes may favor the formation of dimers over complexes with higher cyclic symmetry, through a mechanism of prepositioned pairs of interacting residues. However, examples have been found for all of the crystallographic point groups, demonstrating that functional need can drive the evolution of any symmetry.

Hydrogen bonding interactions in PN...HX complexes: DFT and ab initio studies of structure, properties and topology.

PubMed

Varadwaj, Pradeep Risikrishna

2010-05-01

Spin-restricted DFT (X3LYP and B3LYP) and ab initio (MP2(fc) and CCSD(fc)) calculations in conjunction with the Aug-CC-pVDZ and Aug-CC-pVTZ basis sets were performed on a series of hydrogen bonded complexes PN...HX (X = F, Cl, Br) to examine the variations of their equilibrium gas phase structures, energetic stabilities, electronic properties, and vibrational characteristics in their electronic ground states. In all cases the complexes were predicted to be stable with respect to the constituent monomers. The interaction energy (Delta E) calculated using a super-molecular model is found to be in this order: PN...HF > PN...HCl > PN...HBr in the series examined. Analysis of various physically meaningful contributions arising from the Kitaura-Morokuma (KM) and reduced variational space self-consistent-field (RVS-SCF) energy decomposition procedures shows that the electrostatic energy has significant contribution to the over-all interaction energy. Dipole moment enhancement (Delta mu) was observed in these complexes expected of predominant dipole-dipole electrostatic interaction and was found to follow the trend PN...HF > PN...HCl > PN...HBr at the CCSD level. However, the DFT (X3LYP and B3LYP) and MP2 levels less accurately determined these values (in this order HF < HCl < HBr). Examination of the harmonic vibrational modes reveals that the PN and HX bands exhibit characteristic blue- and red shifts with concomitant bond contraction and elongation, respectively, on hydrogen bond formation. The topological or critical point (CP) analysis using the static quantum theory of atoms in molecules (QTAIM) of Bader was considered to classify and to gain further insight into the nature of interaction existing in the monomers PN and HX, and between them on H-bond formation. It is found from the analysis of the electron density rho ( c ), the Laplacian of electron charge density nabla(2)rho(c), and the total energy density (H ( c )) at the critical points between the interatomic regions that the interaction N...H is indeed electrostatic in origin (rho(c) > 0, nabla(2)rho(c) > 0 and H(c) > 0 at the BCP) whilst the bonds in PN (rho(c) > 0, nabla(2)rho(c) > 0 and H(c) < 0) and HX ((rho(c) > 0, nabla(2)rho(c) < 0 and H(c) < 0)) are predominantly covalent. A natural bond orbital (NBO) analysis of the second order perturbation energy lowering, E((2)), caused by charge transfer mechanism shows that the interaction N...H is n(N) --> BD*(HX) delocalization.

Multiply Intercalator-Substituted Cu(II) Cyclen Complexes as DNA Condensers and DNA/RNA Synthesis Inhibitors.

PubMed

Hormann, Jan; Malina, Jaroslav; Lemke, Oliver; Hülsey, Max J; Wedepohl, Stefanie; Potthoff, Jan; Schmidt, Claudia; Ott, Ingo; Keller, Bettina G; Brabec, Viktor; Kulak, Nora

2018-05-07

Many drugs that are applied in anticancer therapy such as the anthracycline doxorubicin contain DNA-intercalating 9,10-anthraquinone (AQ) moieties. When Cu(II) cyclen complexes were functionalized with up to three (2-anthraquinonyl)methyl substituents, they efficiently inhibited DNA and RNA synthesis resulting in high cytotoxicity (selective for cancer cells) accompanied by DNA condensation/aggregation phenomena. Molecular modeling suggests an unusual bisintercalation mode with only one base pair between the two AQ moieties and the metal complex as a linker. A regioisomer, in which the AQ moieties point in directions unfavorable for such an interaction, had a much weaker biological activity. The ligands alone and corresponding Zn(II) complexes (used as redox inert control compounds) also exhibited lower activity.

Factors influencing flow steadiness in laminar boundary layer shock interactions

NASA Astrophysics Data System (ADS)

Tumuklu, Ozgur; Levin, Deborah A.; Gimelshein, Sergey F.; Austin, Joanna M.

2016-11-01

The Direct Simulation Monte Carlo method has been used to model laminar shock wave boundary interactions of hypersonic flow over a 30/55-deg double-wedge and "tick-shaped" model configurations studied in the Hypervelocity Expansion Tube facility and T-ADFA free-piston shock tunnel, respectively. The impact of thermochemical effects on these interactions by changing the chemical composition from nitrogen to air as well as argon for a stagnation enthalpy of 8.0 MJ/kg flow are investigated using the 2-D wedge model. The simulations are found to reproduce many of the classic features related to Edney Type V strong shock interactions that include the attached, oblique shock formed over the first wedge, the detached bow shock from the second wedge, the separation zone, and the separation and reattachment shocks that cause complex features such as the triple point for both cases. However, results of a reacting air flow case indicate that the size of the separation length, and the movement of the triple point toward to the leading edge is much less than the nitrogen case.

SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex.

PubMed

Chen, Xiaojuan; Yang, Xingxing; Zheng, Yang; Yang, Yudong; Xing, Yaling; Chen, Zhongbin

2014-05-01

SARS coronavirus (SARS-CoV) develops an antagonistic mechanism by which to evade the antiviral activities of interferon (IFN). Previous studies suggested that SARS-CoV papain-like protease (PLpro) inhibits activation of the IRF3 pathway, which would normally elicit a robust IFN response, but the mechanism(s) used by SARS PLpro to inhibit activation of the IRF3 pathway is not fully known. In this study, we uncovered a novel mechanism that may explain how SARS PLpro efficiently inhibits activation of the IRF3 pathway. We found that expression of the membrane-anchored PLpro domain (PLpro-TM) from SARS-CoV inhibits STING/TBK1/IKKε-mediated activation of type I IFNs and disrupts the phosphorylation and dimerization of IRF3, which are activated by STING and TBK1. Meanwhile, we showed that PLpro-TM physically interacts with TRAF3, TBK1, IKKε, STING, and IRF3, the key components that assemble the STING-TRAF3-TBK1 complex for activation of IFN expression. However, the interaction between the components in STING-TRAF3-TBK1 complex is disrupted by PLpro-TM. Furthermore, SARS PLpro-TM reduces the levels of ubiquitinated forms of RIG-I, STING, TRAF3, TBK1, and IRF3 in the STING-TRAF3-TBK1 complex. These results collectively point to a new mechanism used by SARS-CoV through which PLpro negatively regulates IRF3 activation by interaction with STING-TRAF3-TBK1 complex, yielding a SARS-CoV countermeasure against host innate immunity.

A ruthenium anticancer compound interacts with histones and impacts differently on epigenetic and death pathways compared to cisplatin

PubMed Central

Capuozzo, Antonelle; Ali, Moussa; Santamaria, Rita; Armant, Olivier; Delalande, Francois; Dorsselaer, Alain Van; Cianferani, Sarah; Spencer, John; Pfeffer, Michel; Mellitzer, Georg; Gaiddon, Christian

2017-01-01

Ruthenium complexes are considered as potential replacements for platinum compounds in oncotherapy. Their clinical development is handicapped by a lack of consensus on their mode of action. In this study, we identify three histones (H3.1, H2A, H2B) as possible targets for an anticancer redox organoruthenium compound (RDC11). Using purified histones, we confirmed an interaction between the ruthenium complex and histones that impacted on histone complex formation. A comparative study of the ruthenium complex versus cisplatin showed differential epigenetic modifications on histone H3 that correlated with differential expression of histone deacetylase (HDAC) genes. We then characterized the impact of these epigenetic modifications on signaling pathways employing a transcriptomic approach. Clustering analyses showed gene expression signatures specific for cisplatin (42%) and for the ruthenium complex (30%). Signaling pathway analyses pointed to specificities distinguishing the ruthenium complex from cisplatin. For instance, cisplatin triggered preferentially p53 and folate biosynthesis while the ruthenium complex induced endoplasmic reticulum stress and trans-sulfuration pathways. To further understand the role of HDACs in these regulations, we used suberanilohydroxamic acid (SAHA) and showed that it synergized with cisplatin cytotoxicity while antagonizing the ruthenium complex activity. This study provides critical information for the characterization of signaling pathways differentiating both compounds, in particular, by the identification of a non-DNA direct target for an organoruthenium complex. PMID:27935863

Congestion relaxation due to density-dependent junction rules in TASEP network

NASA Astrophysics Data System (ADS)

Tannai, Takahiro; Nishinari, Katsuhiro

2017-09-01

We now consider a small network module of Totally Asymmetric Simple Exclusion Process with branching and aggregation points, and rules of junctions dependent on the densities of segments of the network module. We also focus on the interaction among junctions which are branching and aggregation. The interaction among junctions with density-dependent rules possesses more complexity than those with density-independent rules studied in the previous papers. In conclusion, we confirm the result that density-dependent rules enable vehicles to move more effectively than the density-independent rules.

Exploring pathway interactions in insulin resistant mouse liver

PubMed Central

2011-01-01

Background Complex phenotypes such as insulin resistance involve different biological pathways that may interact and influence each other. Interpretation of related experimental data would be facilitated by identifying relevant pathway interactions in the context of the dataset. Results We developed an analysis approach to study interactions between pathways by integrating gene and protein interaction networks, biological pathway information and high-throughput data. This approach was applied to a transcriptomics dataset to investigate pathway interactions in insulin resistant mouse liver in response to a glucose challenge. We identified regulated pathway interactions at different time points following the glucose challenge and also studied the underlying protein interactions to find possible mechanisms and key proteins involved in pathway cross-talk. A large number of pathway interactions were found for the comparison between the two diet groups at t = 0. The initial response to the glucose challenge (t = 0.6) was typed by an acute stress response and pathway interactions showed large overlap between the two diet groups, while the pathway interaction networks for the late response were more dissimilar. Conclusions Studying pathway interactions provides a new perspective on the data that complements established pathway analysis methods such as enrichment analysis. This study provided new insights in how interactions between pathways may be affected by insulin resistance. In addition, the analysis approach described here can be generally applied to different types of high-throughput data and will therefore be useful for analysis of other complex datasets as well. PMID:21843341

Demystifying the cytokine network: Mathematical models point the way.

PubMed

Morel, Penelope A; Lee, Robin E C; Faeder, James R

2017-10-01

Cytokines provide the means by which immune cells communicate with each other and with parenchymal cells. There are over one hundred cytokines and many exist in families that share receptor components and signal transduction pathways, creating complex networks. Reductionist approaches to understanding the role of specific cytokines, through the use of gene-targeted mice, have revealed further complexity in the form of redundancy and pleiotropy in cytokine function. Creating an understanding of the complex interactions between cytokines and their target cells is challenging experimentally. Mathematical and computational modeling provides a robust set of tools by which complex interactions between cytokines can be studied and analyzed, in the process creating novel insights that can be further tested experimentally. This review will discuss and provide examples of the different modeling approaches that have been used to increase our understanding of cytokine networks. This includes discussion of knowledge-based and data-driven modeling approaches and the recent advance in single-cell analysis. The use of modeling to optimize cytokine-based therapies will also be discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

An uracil-linked hydroxyflavone probe for the recognition of ATP

PubMed Central

Bojtár, Márton; Janzsó-Berend, Péter Zoltán; Mester, Dávid; Hessz, Dóra; Kállay, Mihály; Kubinyi, Miklós

2018-01-01

Background: Nucleotides are essential molecules in living systems due to their paramount importance in various physiological processes. In the past years, numerous attempts were made to selectively recognize and detect these analytes, especially ATP using small-molecule fluorescent chemosensors. Despite the various solutions, the selective detection of ATP is still challenging due to the structural similarity of various nucleotides. In this paper, we report the conjugation of a uracil nucleobase to the known 4’-dimethylamino-hydroxyflavone fluorophore. Results: The complexation of this scaffold with ATP is already known. The complex is held together by stacking and electrostatic interactions. To achieve multi-point recognition, we designed the uracil-appended version of this probe to include complementary base-pairing interactions. The theoretical calculations revealed the availability of multiple complex structures. The synthesis was performed using click chemistry and the nucleotide recognition properties of the probe were evaluated using fluorescence spectroscopy. Conclusions: The first, uracil-containing fluorescent ATP probe based on a hydroxyflavone fluorophore was synthesized and evaluated. A selective complexation with ATP was observed and a ratiometric response in the excitation spectrum. PMID:29719572

Control-structure interaction in precision pointing servo loops

NASA Technical Reports Server (NTRS)

Spanos, John T.

1989-01-01

The control-structure interaction problem is addressed via stability analysis of a generic linear servo loop model. With the plant described by the rigid body mode and a single elastic mode, structural flexibility is categorized into one of three types: (1) appendage, (2) in-the-loop minimum phase, and (3) in-the-loop nonminimum phase. Closing the loop with proportional-derivative (PD) control action and introducing sensor roll-off dynamics in the feedback path, stability conditions are obtained. Trade studies are conducted with modal frequency, modal participation, modal damping, loop bandwidth, and sensor bandwidth treated as free parameters. Results indicate that appendage modes are most likely to produce instability if they are near the sensor rolloff, whereas in-the-loop modes are most dangerous near the loop bandwidth. The main goal of this paper is to provide a fundamental understanding of the control-structure interaction problem so that it may benefit the design of complex spacecraft and pointing system servo loops. In this framework, the JPL Pathfinder gimbal pointer is considered as an example.

Modeling propellant-based stimulation of a borehole with peridynamics

DOE PAGES

Panchadhara, Rohan; Gordon, Peter A.; Parks, Michael L.

2017-02-27

A non-local formulation of classical continuum mechanics theory known as peridynamics is used to study fracture initiation and growth from a wellbore penetrating the subsurface within the context of propellant-based stimulation. The principal objectives of this work are to analyze the influence of loading conditions on the resulting fracture pattern, to investigate the effect of in-situ stress anisotropy on fracture propagation, and to assess the suitability of peridynamics for modeling complex fracture formation. In peridynamics, the momentum equation from the classical theory of solid mechanics is replaced by a non-local analogue, which results in an integrodifferential conservation equation. A continuummore » material is discretized with a set of material points that interact with all other points within a specified distance. Interactions between points are governed by bonds that can deform and break depending on loading conditions. The accumulated breakage of bonds gives rise to a picture of complex growth of fractures that is seen as a key advantage in the peridynamic representation of discontinuities. It is shown that the loading rate significantly influences the number and ex- tent of fractures initiated from a borehole. Results show that low loading rates produce fewer but longer fractures, whereas high loading rates produce numerous shorter fractures around the borehole. The numerical method is able to predict fracture growth patterns over a wide range of loading and stress conditions. Our results also show that fracture growth is attenuated with increasing in-situ confining stress, and, in the case of confining stress anisotropy, fracture extensions are largest in the direction perpendicular to the minimum compressive stress. Since the results are in broad qualitative agreement with experimental and numerical studies found in the literature, suggesting that peridynamics can be a powerful tool in the study of complex fracture network formation.« less

Modeling propellant-based stimulation of a borehole with peridynamics

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

Panchadhara, Rohan; Gordon, Peter A.; Parks, Michael L.

A non-local formulation of classical continuum mechanics theory known as peridynamics is used to study fracture initiation and growth from a wellbore penetrating the subsurface within the context of propellant-based stimulation. The principal objectives of this work are to analyze the influence of loading conditions on the resulting fracture pattern, to investigate the effect of in-situ stress anisotropy on fracture propagation, and to assess the suitability of peridynamics for modeling complex fracture formation. In peridynamics, the momentum equation from the classical theory of solid mechanics is replaced by a non-local analogue, which results in an integrodifferential conservation equation. A continuummore » material is discretized with a set of material points that interact with all other points within a specified distance. Interactions between points are governed by bonds that can deform and break depending on loading conditions. The accumulated breakage of bonds gives rise to a picture of complex growth of fractures that is seen as a key advantage in the peridynamic representation of discontinuities. It is shown that the loading rate significantly influences the number and ex- tent of fractures initiated from a borehole. Results show that low loading rates produce fewer but longer fractures, whereas high loading rates produce numerous shorter fractures around the borehole. The numerical method is able to predict fracture growth patterns over a wide range of loading and stress conditions. Our results also show that fracture growth is attenuated with increasing in-situ confining stress, and, in the case of confining stress anisotropy, fracture extensions are largest in the direction perpendicular to the minimum compressive stress. Since the results are in broad qualitative agreement with experimental and numerical studies found in the literature, suggesting that peridynamics can be a powerful tool in the study of complex fracture network formation.« less

Molecular Dynamics in Mixed Solvents Reveals Protein-Ligand Interactions, Improves Docking, and Allows Accurate Binding Free Energy Predictions.

PubMed

Arcon, Juan Pablo; Defelipe, Lucas A; Modenutti, Carlos P; López, Elias D; Alvarez-Garcia, Daniel; Barril, Xavier; Turjanski, Adrián G; Martí, Marcelo A

2017-04-24

One of the most important biological processes at the molecular level is the formation of protein-ligand complexes. Therefore, determining their structure and underlying key interactions is of paramount relevance and has direct applications in drug development. Because of its low cost relative to its experimental sibling, molecular dynamics (MD) simulations in the presence of different solvent probes mimicking specific types of interactions have been increasingly used to analyze protein binding sites and reveal protein-ligand interaction hot spots. However, a systematic comparison of different probes and their real predictive power from a quantitative and thermodynamic point of view is still missing. In the present work, we have performed MD simulations of 18 different proteins in pure water as well as water mixtures of ethanol, acetamide, acetonitrile and methylammonium acetate, leading to a total of 5.4 μs simulation time. For each system, we determined the corresponding solvent sites, defined as space regions adjacent to the protein surface where the probability of finding a probe atom is higher than that in the bulk solvent. Finally, we compared the identified solvent sites with 121 different protein-ligand complexes and used them to perform molecular docking and ligand binding free energy estimates. Our results show that combining solely water and ethanol sites allows sampling over 70% of all possible protein-ligand interactions, especially those that coincide with ligand-based pharmacophoric points. Most important, we also show how the solvent sites can be used to significantly improve ligand docking in terms of both accuracy and precision, and that accurate predictions of ligand binding free energies, along with relative ranking of ligand affinity, can be performed.

Physical interaction of human T-cell leukemia virus type 1 Tax with cyclin-dependent kinase 4 stimulates the phosphorylation of retinoblastoma protein.

PubMed

Haller, Kerstin; Wu, Yalin; Derow, Elisabeth; Schmitt, Iris; Jeang, Kuan-Teh; Grassmann, Ralph

2002-05-01

The Tax oncoprotein of human T-cell leukemia virus type 1 (HTLV-1) induces leukemia in transgenic mice and permanent T-cell growth in vitro. In transformed lymphocytes, it acts as an essential growth factor. Tax stimulates the cell cycle in the G(1) phase by activating the cyclin-dependent kinase (CDK) CDK4 and CDK6 holoenzyme complexes. Here we show that Tax directly interacts with CDK4. This binding to CDK4 was specific, since Tax did not bind to either CDK2 or CDK1. The interaction with CDK4/cyclin D complexes was observed in vitro, in transfected fibroblasts, in HTLV-1-infected T cells, and in adult T-cell leukemia-derived cultures. Binding studies with several point and deletion mutants indicated that the N terminus of Tax mediates the interaction with CDK4. The Tax/CDK complex represented an active holoenzyme which capably phosphorylates the Rb protein in vitro and is resistant to repression by the inhibitor p21(CIP). Binding-deficient Tax mutants failed to activate CDK4, indicating that direct association with Tax is required for enhanced kinase activity. Tax also increased the association of CDK4 with its positive cyclin regulatory subunit. Thus, protein-protein contact between Tax and the components of the cyclin D/CDK complexes provides a further mechanistic explanation for the mitogenic and immortalizing effects of this HTLV-1 oncoprotein.

Physical Interaction of Human T-Cell Leukemia Virus Type 1 Tax with Cyclin-Dependent Kinase 4 Stimulates the Phosphorylation of Retinoblastoma Protein

PubMed Central

Haller, Kerstin; Wu, Yalin; Derow, Elisabeth; Schmitt, Iris; Jeang, Kuan-Teh; Grassmann, Ralph

2002-01-01

The Tax oncoprotein of human T-cell leukemia virus type 1 (HTLV-1) induces leukemia in transgenic mice and permanent T-cell growth in vitro. In transformed lymphocytes, it acts as an essential growth factor. Tax stimulates the cell cycle in the G1 phase by activating the cyclin-dependent kinase (CDK) CDK4 and CDK6 holoenzyme complexes. Here we show that Tax directly interacts with CDK4. This binding to CDK4 was specific, since Tax did not bind to either CDK2 or CDK1. The interaction with CDK4/cyclin D complexes was observed in vitro, in transfected fibroblasts, in HTLV-1-infected T cells, and in adult T-cell leukemia-derived cultures. Binding studies with several point and deletion mutants indicated that the N terminus of Tax mediates the interaction with CDK4. The Tax/CDK complex represented an active holoenzyme which capably phosphorylates the Rb protein in vitro and is resistant to repression by the inhibitor p21CIP. Binding-deficient Tax mutants failed to activate CDK4, indicating that direct association with Tax is required for enhanced kinase activity. Tax also increased the association of CDK4 with its positive cyclin regulatory subunit. Thus, protein-protein contact between Tax and the components of the cyclin D/CDK complexes provides a further mechanistic explanation for the mitogenic and immortalizing effects of this HTLV-1 oncoprotein. PMID:11971966

Cu+ association to some Ph-X (X = OH, NH2, CHO, COOH, CF3) phenyl derivatives.: A comparison with Li+ complexes

NASA Astrophysics Data System (ADS)

Corral, Ines; Mo, Otilia; Yanez, Manuel

2006-09-01

The complexes of Cu+ with phenol, aniline, benzaldehyde, benzoic acid, and trifluromethyl-benzene were investigated through the use of MP2 and density functional theory (DFT) methods. Both harmonic vibrational frequencies and optimized geometries were obtained at the B3LYP/6-311G(d,p) and MP2(full)/6-311G(d,p) levels of theory. Final energies were obtained through single point B3LYP/6-311+G(3df,2p)//B3LYP/6-311G(d,p) calculations. The interactions of Cu+ with these aromatic compounds have a non-negligible covalent character, which clearly differentiate Cu+-complexes from the corresponding Li+-complexes. These dissimilarities are reflected in the geometries, binding energies and infrared spectra of the most stable adducts. For Li+ only conventional [pi]-complexes should be expected when interacting with aniline, while Cu+ attaches preferentially to the para carbon atom. For phenol, besides the conventional [pi]-complexes, a 12% of oxygen attached species are expected to be found upon Li+ association. Conversely, no oxygen attached species should be formed in reactions of phenol with Cu+. For benzoic acid and benzaldehyde, Li+ aligns with the dipole moment of the base, interacting exclusively with the carbonyl oxygen in the plane of the molecule. This is also the case in Cu+-benzoic acid complex, while in the Cu+-benzaldehyde complex the metal ion also interacts with the aromatic [pi]-system. Cu+ binding enthalpies (BEs) are systematically larger (about 1.3 times) than Li+ BEs. The covalent character of Cu+ interactions is associated with electron donations from bonding ([pi]) orbitals or lone-pairs of the base toward the 4s empty orbital of the metal and with back-donations from the occupied d orbitals of the metal toward antibonding ([pi]*) empty orbitals of the base. This non-negligible covalent character is also reflected in a rough correlation between the calculated Cu+ BEs and the available experimental proton affinities that does not exist for Li+ BEs.

Empowering L2 Tutoring: A Case Study of a Second Language Writer's Vocabulary Learning

ERIC Educational Resources Information Center

Severino, Carol; Deifell, Elizabeth

2011-01-01

Writing center tutors play a key role in advancing L2 writers' language learning because the tutorial interaction involves the introduction of new language and vocabulary at the point of need or interest. This tutor-research case study presents a detailed, complex portrait of how a second language writer in a US writing center learned and used…

Making Graphical Inferences: A Hierarchical Framework

DTIC Science & Technology

2004-08-01

from graphs is considered one of the more complex skills graph readers should possess. According to the National Council of Teachers of Mathematics ...understanding graphical perception. Human Computer Interaction, 8, 353-388. NCTM : Standards for Mathematics . (2003, 2003). Pinker, S. (1990). A theory... NCTM ) the simplest type of question involves the extraction or comparison of a few explicitly represented data points (read-offs) ( NCTM : Standards

Existence of both blue-shifting hydrogen bond and Lewis acid-base interaction in the complexes of carbonyls and thiocarbonyls with carbon dioxide.

PubMed

Nguyen, Tien Trung; Nguyen, Phi Hung; Tran, Thanh Hue; Minh, Tho Nguyen

2011-08-21

In this study, 16 gas phase complexes of the pairs of XCHZ and CO(2) (X = F, Cl, Br; Z = O, S) have been identified. Interaction energies calculated at the CCSD(T)/aug-cc-pVTZ//MP2/aug-cc-pVTZ level including both BSSE and ZPE corrections range from -5.6 to -10.5 kJ mol(-1) for XCHOCO(2) and from -5.7 to -9.1 kJ mol(-1) for XCHS···CO(2). Substitution of one H atom by one halogen in formaldehyde and thioformaldehyde reduces the interaction energy of XCHZ···CO(2), while a CH(3) substitution increases the interaction energy of both CH(3)CHO···CO(2) and CH(3)CHS···CO(2). NBO and AIM analyses also point out that the strength of Lewis acid-base interactions decreases going from >C1=S3···C6 to >C1=O3C6 and to >C1-X4···C6. This result suggests the higher capacity of solubility of thiocarbonyl compounds in scCO(2), providing an enormous potential application for designing CO(2)-philic materials based on the >C=S functional group in competition with >C=O. The Lewis acid-base interaction of the types >C=S···C, >C-Cl···C and >C-Br···C is demonstrated for the first time. The contribution of the hydrogen bonding interaction to the total interaction energy is larger for XCHS···CO(2) than for XCHO···CO(2). Upon complexation, a contraction of the C1-H2 bond length and a blue shift of its stretching frequency have been observed, as compared to the isolated monomer, indicating the existence of a blue-shifting hydrogen bond in all complexes examined. Calculated results also lend further support for the viewpoint that when acting as proton donor, a C-H bond having a weaker polarization will induce a stronger distance contraction and frequency blue shift upon complexation, and vice versa.

Local spatial frequency analysis for computer vision

NASA Technical Reports Server (NTRS)

Krumm, John; Shafer, Steven A.

1990-01-01

A sense of vision is a prerequisite for a robot to function in an unstructured environment. However, real-world scenes contain many interacting phenomena that lead to complex images which are difficult to interpret automatically. Typical computer vision research proceeds by analyzing various effects in isolation (e.g., shading, texture, stereo, defocus), usually on images devoid of realistic complicating factors. This leads to specialized algorithms which fail on real-world images. Part of this failure is due to the dichotomy of useful representations for these phenomena. Some effects are best described in the spatial domain, while others are more naturally expressed in frequency. In order to resolve this dichotomy, we present the combined space/frequency representation which, for each point in an image, shows the spatial frequencies at that point. Within this common representation, we develop a set of simple, natural theories describing phenomena such as texture, shape, aliasing and lens parameters. We show these theories lead to algorithms for shape from texture and for dealiasing image data. The space/frequency representation should be a key aid in untangling the complex interaction of phenomena in images, allowing automatic understanding of real-world scenes.

Uncertainty Reduction for Stochastic Processes on Complex Networks

NASA Astrophysics Data System (ADS)

Radicchi, Filippo; Castellano, Claudio

2018-05-01

Many real-world systems are characterized by stochastic dynamical rules where a complex network of interactions among individual elements probabilistically determines their state. Even with full knowledge of the network structure and of the stochastic rules, the ability to predict system configurations is generally characterized by a large uncertainty. Selecting a fraction of the nodes and observing their state may help to reduce the uncertainty about the unobserved nodes. However, choosing these points of observation in an optimal way is a highly nontrivial task, depending on the nature of the stochastic process and on the structure of the underlying interaction pattern. In this paper, we introduce a computationally efficient algorithm to determine quasioptimal solutions to the problem. The method leverages network sparsity to reduce computational complexity from exponential to almost quadratic, thus allowing the straightforward application of the method to mid-to-large-size systems. Although the method is exact only for equilibrium stochastic processes defined on trees, it turns out to be effective also for out-of-equilibrium processes on sparse loopy networks.

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

The basic amino acids in the coiled-coil domain of CIN85 regulate its interaction with c-Cbl and phosphatidic acid during epidermal growth factor receptor (EGFR) endocytosis.

PubMed

Zheng, Xiudan; Zhang, Jing; Liao, Kan

2014-07-08

During EGFR internalization CIN85 bridges EGFR-Cbl complex, endocytic machinery and fusible membrane through the interactions of CIN85 with c-Cbl, endophilins and phosphatidic acid. These protein-protein and protein-lipid interactions are mediated or regulated by the positively charged C-terminal coiled-coil domain of CIN85. However, the details of CIN85-lipid interaction remain unknown. The present study suggested a possible electric interaction between the negative charge of phosphatidic acid and the positive charge of basic amino acids in coiled-coil domain. Mutations of the basic amino acids in the coiled-coil domain, especially K645, K646, R648 and R650, into neutral amino acid alanine completely blocked the interaction of CIN85 with c-Cbl or phosphatidic acid. However, they did not affect CIN85-endophilin interaction. In addition, CIN85 was found to associate with the internalized EGFR endosomes. It interacted with several ESCRT (Endosomal Sorting Complex Required for Transport) component proteins for ESCRT assembly on endosomal membrane. Mutations in the coiled-coil domain (deletion of the coiled-coil domain or point mutations of the basic amino acids) dissociated CIN85 from endosomes. These mutants bound the ESCRT components in cytoplasm to prevent them from assembly on endosomal membrane and inhibited EGFR sorting for degradation. As an adaptor protein, CIN85 interacts with variety of partners through several domains. The positive charges of basic amino acids in the coiled-coil domain are not only involved in the interaction with phosphatidic acid, but also regulate the interaction of CIN85 with c-Cbl. CIN85 also interacts with ESCRT components for protein sorting in endosomes. These CIN85-protein and CIN85-lipid interactions enable CIN85 to link EGFR-Cbl endocytic complex with fusible membrane during EGFR endocytosis and subsequently to facilitate ESCRT formation on endosomal membrane for EGFR sorting and degradation.

Interactive orbital proximity operations planning system

NASA Technical Reports Server (NTRS)

Grunwald, Arthur J.; Ellis, Stephen R.

1988-01-01

An interactive graphical proximity operations planning system was developed, which allows on-site design of efficient, complex, multiburn maneuvers in a dynamic multispacecraft environment. Maneuvering takes place in and out of the orbital plane. The difficulty in planning such missions results from the unusual and counterintuitive character of orbital dynamics and complex time-varying operational constraints. This difficulty is greatly overcome by visualizing the relative trajectories and the relevant constraints in an easily interpretable graphical format, which provides the operator with immediate feedback on design actions. The display shows a perspective bird's-eye view of a Space Station and co-orbiting spacecraft on the background of the Station's orbital plane. The operator has control over the two modes of operation: a viewing system mode, which enables the exporation of the spatial situation about the Space Station and thus the ability to choose and zoom in on areas of interest; and a trajectory design mode, which allows the interactive editing of a series of way points and maneuvering burns to obtain a trajectory that complies with all operational constraints. A first version of this display was completed. An experimental program is planned in which operators will carry out a series of design missions which vary in complexity and constraints.

Coevolving complex networks in the model of social interactions

NASA Astrophysics Data System (ADS)

Raducha, Tomasz; Gubiec, Tomasz

2017-04-01

We analyze Axelrod's model of social interactions on coevolving complex networks. We introduce four extensions with different mechanisms of edge rewiring. The models are intended to catch two kinds of interactions-preferential attachment, which can be observed in scientists or actors collaborations, and local rewiring, which can be observed in friendship formation in everyday relations. Numerical simulations show that proposed dynamics can lead to the power-law distribution of nodes' degree and high value of the clustering coefficient, while still retaining the small-world effect in three models. All models are characterized by two phase transitions of a different nature. In case of local rewiring we obtain order-disorder discontinuous phase transition even in the thermodynamic limit, while in case of long-distance switching discontinuity disappears in the thermodynamic limit, leaving one continuous phase transition. In addition, we discover a new and universal characteristic of the second transition point-an abrupt increase of the clustering coefficient, due to formation of many small complete subgraphs inside the network.

Fluorometric and theoretical studies on inclusion complexes of β-cyclodextrin and D-, L-phenylalanine

NASA Astrophysics Data System (ADS)

Aree, Thammarat; Arunchai, Rungthiwa; Koonrugsa, Narongsak; Intasiri, Amarawan

2012-10-01

Inclusion complexes of β-cyclodextrin (β-CD) with L- and D-phenylalanine (Phe) have been characterized in solution by fluorometry and in gas phase by semiempirical PM3 calculations. The unimolar stoichiometric ratio of both β-CD-L-Phe and β-CD-D-Phe complexes and the stability constants (K) were deduced from fluorometric titrations. The β-CD-L-Phe complex is more stable than the β-CD-D-Phe complex as indicated by the larger K values, 21.1 vs. 6.86 M-1. This is consistent with the stabilization energies (ΔEstb) and inclusion geometries obtained from PM3 calculations. The β-CD-L-Phe complex with L-Phe residing in the central β-CD cavity and pointing its COOH group downwards to the O6 end has ΔEstb = -62.7 kJ mol-1, whereas the β-CD-D-Phe complex with D-Phe placing at 3 Å beneath the β-CD O4-plane and pointing its COOH group upwards to the O2/O3 end has ΔEstb = -53.3 kJ mol-1. The unison of host-guest intermolecular hydrogen bonds, hydrophobic interactions and molecular deformations plays an essential role in forming and stabilizing the inclusion complexes. Our results show that the β-CD-L-Phe and β-CD-D-Phe inclusion complexes are relatively stable and differentiable, suggesting the applications of CDs in foods and drugs.

SmartHome: a domotic framework based on smart sensing and actuator network to reduce energy wastes

NASA Astrophysics Data System (ADS)

Santamaria, Amilcare Francesco; De Rango, Floriano; Falbo, Domenico; Barletta, Domenico

2014-05-01

Domestic environment and human interaction with services supplied by domotic devices is going to be a very interesting application field. With a domotic system is possible to achieve great interaction between human beings, environments and smart devices. The enhancing of these interactions is the main goal of this work whose intent is to improve the classic concept of domotics. The framework we developed can be used for several application fields such as lighting, heating, conditioning or water management and energy consumption. In particular, the proposed system can optimize energy consumptions by rising awareness to users that have full control of their house and the possibility to save money and reduce the impact of the energetic consumes to the earth, matching the new "green" motto requirements. In this way, the overall system wants to match the central concept of Internet Of Things (IoT) as well. From this point of view a complex automation system with smart devices make possible a more efficient way to produce, follow and manage domotic policies. Following the spread of IoT, for this work we designed and implemented new plug-and-play and ready-to-use smart devices that are part of a complex automation system that offers a user-friendly web application and allows users to control and interact with different plans of their house in order to make life more comfortable and be aware of their energy consumptions. Control and awareness arc the two key points that led us to develop the proposed system.

Identification of amino acids that promote specific and rigid TAR RNA-tat protein complex formation.

PubMed

Edwards, Thomas E; Robinson, Bruce H; Sigurdsson, Snorri Th

2005-03-01

The Tat protein and the transactivation responsive (TAR) RNA form an essential complex in the HIV lifecycle, and mutations in the basic region of the Tat protein alter this RNA-protein molecular recognition. Here, EPR spectroscopy was used to identify amino acids, flanking an essential arginine of the Tat protein, which contribute to specific and rigid TAR-Tat complex formation by monitoring changes in the mobility of nitroxide spin-labeled TAR RNA nucleotides upon binding. Arginine to lysine N-terminal mutations did not affect TAR RNA interfacial dynamics. In contrast, C-terminal point mutations, R56 in particular, affected the mobility of nucleotides U23 and U38, which are involved in a base-triple interaction in the complex. This report highlights the role of dynamics in specific molecular complex formation and demonstrates the ability of EPR spectroscopy to study interfacial dynamics of macromolecular complexes.

Food-web complexity emerging from ecological dynamics on adaptive networks.

PubMed

Garcia-Domingo, Josep L; Saldaña, Joan

2007-08-21

Food webs are complex networks describing trophic interactions in ecological communities. Since Robert May's seminal work on random structured food webs, the complexity-stability debate is a central issue in ecology: does network complexity increase or decrease food-web persistence? A multi-species predator-prey model incorporating adaptive predation shows that the action of ecological dynamics on the topology of a food web (whose initial configuration is generated either by the cascade model or by the niche model) render, when a significant fraction of adaptive predators is present, similar hyperbolic complexity-persistence relationships as those observed in empirical food webs. It is also shown that the apparent positive relation between complexity and persistence in food webs generated under the cascade model, which has been pointed out in previous papers, disappears when the final connection is used instead of the initial one to explain species persistence.

Action Priority: Early Neurophysiological Interaction of Conceptual and Motor Representations

PubMed Central

Koester, Dirk; Schack, Thomas

2016-01-01

Handling our everyday life, we often react manually to verbal requests or instruction, but the functional interrelations of motor control and language are not fully understood yet, especially their neurophysiological basis. Here, we investigated whether specific motor representations for grip types interact neurophysiologically with conceptual information, that is, when reading nouns. Participants performed lexical decisions and, for words, executed a grasp-and-lift task on objects of different sizes involving precision or power grips while the electroencephalogram was recorded. Nouns could denote objects that require either a precision or a power grip and could, thus, be (in)congruent with the performed grasp. In a control block, participants pointed at the objects instead of grasping them. The main result revealed an event-related potential (ERP) interaction of grip type and conceptual information which was not present for pointing. Incongruent compared to congruent conditions elicited an increased positivity (100–200 ms after noun onset). Grip type effects were obtained in response-locked analyses of the grasping ERPs (100–300 ms at left anterior electrodes). These findings attest that grip type and conceptual information are functionally related when planning a grasping action but such an interaction could not be detected for pointing. Generally, the results suggest that control of behaviour can be modulated by task demands; conceptual noun information (i.e., associated action knowledge) may gain processing priority if the task requires a complex motor response. PMID:27973539

Influence of the Li···π Interaction on the H/X···π Interactions in HOLi···C6H6···HOX/XOH (X=F, Cl, Br, I) complexes.

PubMed

Zeng, Yanli; Wu, Wenjie; Li, Xiaoyan; Zheng, Shijun; Meng, Lingpeng

2013-06-03

The influences of the Li···π interaction of C6H6···LiOH on the H···π interaction of C6H6···HOX (X=F, Cl, Br, I) and the X···π interaction of C6H6···XOH (X=Cl, Br, I) are investigated by means of full electronic second-order Møller-Plesset perturbation theory calculations and "quantum theory of atoms in molecules" (QTAIM) studies. The binding energies, binding distances, infrared vibrational frequencies, and electron densities at the bond critical points (BCPs) of the hydrogen bonds and halogen bonds prove that the addition of the Li···π interaction to benzene weakens the H···π and X···π interactions. The influences of the Li···π interaction on H···π interactions are greater than those on X···π interactions; the influences of the H···π interactions on the Li···π interaction are greater than X···π interactions on Li···π interaction. The greater the influence of Li···π interaction on H/X···π interactions, the greater the influences of H/X···π interactions on Li···π interaction. QTAIM studies show that the intermolecular interactions of C6H6···HOX and C6H6···XOH are mainly of the π type. The electron densities at the BCPs of hydrogen bonds and halogen bonds decrease on going from bimolecular complexes to termolecular complexes, and the π-electron densities at the BCPs show the same pattern. Natural bond orbital analyses show that the Li···π interaction reduces electron transfer from C6 H6 to HOX and XOH. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Automatic visualization of 3D geometry contained in online databases

NASA Astrophysics Data System (ADS)

Zhang, Jie; John, Nigel W.

2003-04-01

In this paper, the application of the Virtual Reality Modeling Language (VRML) for efficient database visualization is analyzed. With the help of JAVA programming, three examples of automatic visualization from a database containing 3-D Geometry are given. The first example is used to create basic geometries. The second example is used to create cylinders with a defined start point and end point. The third example is used to processs data from an old copper mine complex in Cheshire, United Kingdom. Interactive 3-D visualization of all geometric data in an online database is achieved with JSP technology.

PLUMED-GUI: An environment for the interactive development of molecular dynamics analysis and biasing scripts

NASA Astrophysics Data System (ADS)

Giorgino, Toni

2014-03-01

PLUMED-GUI is an interactive environment to develop and test complex PLUMED scripts within the Visual Molecular Dynamics (VMD) environment. Computational biophysicists can take advantage of both PLUMED’s rich syntax to define collective variables (CVs) and VMD’s chemically-aware atom selection language, while working within a natural point-and-click interface. Pre-defined templates and syntax mnemonics facilitate the definition of well-known reaction coordinates. Complex CVs, e.g. involving reference snapshots used for RMSD or native contacts calculations, can be built through dialogs that provide a synoptic view of the available options. Scripts can be either exported for use in simulation programs, or evaluated on the currently loaded molecular trajectories. Script development takes place without leaving VMD, thus enabling an incremental try-see-modify development model for molecular metrics.

Shock wave/turbulent boundary layer interaction in the flow field of a tri-dimension wind tunnel

NASA Technical Reports Server (NTRS)

Benay, R.; Pot, T.

1986-01-01

The first results of a thorough experimental analysis of a strong three-dimensional shock-wave/turbulent boundary-layer interaction occurring in a three dimensional transonic channel are presented. The aim of this experiment is to help in the physical understanding of a complex field, including several separations, and to provide a well documented case to test computational methods. The flowfield has been probed in many points by means of a three-component laser Doppler velocimeter. The results presented relate only to the mean velocity field. They clearly show the formation in the flow of a strong vortical motion resulting from the shock wave interaction.

Functions of key residues in the ligand-binding pocket of vitamin D receptor: Fragment molecular orbital interfragment interaction energy analysis

NASA Astrophysics Data System (ADS)

Yamagishi, Kenji; Yamamoto, Keiko; Yamada, Sachiko; Tokiwa, Hiroaki

2006-03-01

Fragment molecular orbital-interfragment interaction energy calculations of the vitamin D receptor (VDR)/1α,25-dihydroxyvitamin D 3 complex were utilized to assign functions of key residues of the VDR. Only one residue forms a significant interaction with the corresponding hydroxy group of the ligand, although two residues are located around each hydroxy group. The degradation of binding affinity for derivatives upon removal of a hydroxy group is closely related to the trend in the strength of the hydrogen bonds. Type II hereditary rickets due to an Arg274 point mutation is caused by the lack of the strongest hydrogen bond.

Viewpoints: A New Computer Program for Interactive Exploration of Large Multivariate Space Science and Astrophysics Data.

NASA Astrophysics Data System (ADS)

Levit, Creon; Gazis, P.

2006-06-01

The graphics processing units (GPUs) built in to all professional desktop and laptop computers currently on the market are capable of transforming, filtering, and rendering hundreds of millions of points per second. We present a prototype open-source cross-platform (windows, linux, Apple OSX) application which leverages some of the power latent in the GPU to enable smooth interactive exploration and analysis of large high-dimensional data using a variety of classical and recent techniques. The targeted application area is the interactive analysis of complex, multivariate space science and astrophysics data sets, with dimensionalities that may surpass 100 and sample sizes that may exceed 10^6-10^8.

Generation of amyloid-β is reduced by the interaction of calreticulin with amyloid precursor protein, presenilin and nicastrin.

PubMed

Stemmer, Nina; Strekalova, Elena; Djogo, Nevena; Plöger, Frank; Loers, Gabriele; Lutz, David; Buck, Friedrich; Michalak, Marek; Schachner, Melitta; Kleene, Ralf

2013-01-01

Dysregulation of the proteolytic processing of amyloid precursor protein by γ-secretase and the ensuing generation of amyloid-β is associated with the pathogenesis of Alzheimer's disease. Thus, the identification of amyloid precursor protein binding proteins involved in regulating processing of amyloid precursor protein by the γ-secretase complex is essential for understanding the mechanisms underlying the molecular pathology of the disease. We identified calreticulin as novel amyloid precursor protein interaction partner that binds to the γ-secretase cleavage site within amyloid precursor protein and showed that this Ca(2+)- and N-glycan-independent interaction is mediated by amino acids 330-344 in the C-terminal C-domain of calreticulin. Co-immunoprecipitation confirmed that calreticulin is not only associated with amyloid precursor protein but also with the γ-secretase complex members presenilin and nicastrin. Calreticulin was detected at the cell surface by surface biotinylation of cells overexpressing amyloid precursor protein and was co-localized by immunostaining with amyloid precursor protein and presenilin at the cell surface of hippocampal neurons. The P-domain of calreticulin located between the N-terminal N-domain and the C-domain interacts with presenilin, the catalytic subunit of the γ-secretase complex. The P- and C-domains also interact with nicastrin, another functionally important subunit of this complex. Transfection of amyloid precursor protein overexpressing cells with full-length calreticulin leads to a decrease in amyloid-β42 levels in culture supernatants, while transfection with the P-domain increases amyloid-β40 levels. Similarly, application of the recombinant P- or C-domains and of a synthetic calreticulin peptide comprising amino acid 330-344 to amyloid precursor protein overexpressing cells result in elevated amyloid-β40 and amyloid-β42 levels, respectively. These findings indicate that the interaction of calreticulin with amyloid precursor protein and the γ-secretase complex regulates the proteolytic processing of amyloid precursor protein by the γ-secretase complex, pointing to calreticulin as a potential target for therapy in Alzheimer's disease.

Dynamics in a three species food-web system

NASA Astrophysics Data System (ADS)

Gupta, K.; Gakkhar, S.

2016-04-01

In this paper, the dynamics of a three species food-web system is discussed. The food-web comprises of one predator and two logistically growing competing species. The predator species is taking food from one of the competitors with Holling type II functional response. Another competitor is the amensal species for the predator of first species. The system is shown to be positive and bounded. The stability of various axial points, boundary points and interior point has been investigated. The persistence of the system has been studied. Numerical simulation has been performed to show the occurrence of Hopf bifurcation and stable limit cycle about the interior point. The presence of second competitor and its interaction with predator gives more complex dynamics than the simple prey-predator system. The existence of transcritical bifurcation has been established about two axial points. The existence of periodic attractor having period-2 solution has been shown, when amensal coefficient is chosen as bifurcation parameter.

The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG.

PubMed

de Winter, J P; van der Weel, L; de Groot, J; Stone, S; Waisfisz, Q; Arwert, F; Scheper, R J; Kruyt, F A; Hoatlin, M E; Joenje, H

2000-11-01

Fanconi anemia (FA) is a chromosomal instability syndrome associated with a strong predisposition to cancer, particularly acute myeloid leukemia and squamous cell carcinoma. At the cellular level, FA is characterized by spontaneous chromosomal breakage and a unique hypersensitivity to DNA cross-linking agents. Complementation analysis has indicated that at least seven distinct genes are involved in the pathogenesis of FA. Despite the identification of four of these genes (FANCA, FANCC, FANCF and FANCG), the nature of the 'FA pathway' has remained enigmatic, as the FA proteins lack sequence homologies or motifs that could point to a molecular function. To further define this pathway, we studied the subcellular localizations and mutual interactions of the FA proteins, including the recently identified FANCF protein, in human lymphoblasts. FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG. These interactions were detected in wild-type and FA-D lymphoblasts, but not in lymphoblasts of other FA complementation groups. This implies that each of the FA proteins, except FANCD, is required for these complexes to form. Similarly, we show that the interaction between FANCA and FANCC is restricted to wild-type and FA-D cells. Furthermore, we document the subcellular localization of FANCA and the FANCA/FANCG complex in all FA complementation groups. Our results, along with published data, culminate in a model in which a multi-protein FA complex serves a nuclear function to maintain genomic integrity.

Dilution of protein-surfactant complexes: a fluorescence study.

PubMed

Azadi, Glareh; Chauhan, Anuj; Tripathi, Anubhav

2013-09-01

Dilution of protein-surfactant complexes is an integrated step in microfluidic protein sizing, where the contribution of free micelles to the overall fluorescence is reduced by dilution. This process can be further improved by establishing an optimum surfactant concentration and quantifying the amount of protein based on the fluorescence intensity. To this end, we study the interaction of proteins with anionic sodium dodecyl sulfate (SDS) and cationic hexadecyl trimethyl ammonium bromide (CTAB) using a hydrophobic fluorescent dye (sypro orange). We analyze these interactions fluourometrically with bovine serum albumin, carbonic anhydrase, and beta-galactosidase as model proteins. The fluorescent signature of protein-surfactant complexes at various dilution points shows three distinct regions, surfactant dominant, breakdown, and protein dominant region. Based on the dilution behavior of protein-surfactant complexes, we propose a fluorescence model to explain the contribution of free and bound micelles to the overall fluorescence. Our results show that protein peak is observed at 3 mM SDS as the optimum dilution concentration. Furthermore, we study the effect of protein concentration on fluorescence intensity. In a single protein model with a constant dye quantum yield, the peak height increases with protein concentration. Finally, addition of CTAB to the protein-SDS complex at mole fractions above 0.1 shifts the protein peak from 3 mM to 4 mM SDS. The knowledge of protein-surfactant interactions obtained from these studies provides significant insights for novel detection and quantification techniques in microfluidics. © 2013 The Protein Society.

Studying the dynamics of SLP-76, Nck, and Vav1 multimolecular complex formation in live human cells with triple-color FRET.

PubMed

Pauker, Maor H; Hassan, Nirit; Noy, Elad; Reicher, Barak; Barda-Saad, Mira

2012-04-24

Protein-protein interactions regulate and control many cellular functions. A multimolecular complex consisting of the adaptor proteins SLP-76 (Src homology 2 domain-containing leukocyte protein of 76 kD), Nck, and the guanine nucleotide exchange factor Vav1 is recruited to the T cell side of the interface with an antigen-presenting cell during initial T cell activation. This complex is crucial for regulation of the actin machinery, antigen recognition, and signaling in T cells. We studied the interactions between these proteins as well as the dynamics of their recruitment into a complex that governs cytoskeletal reorganization. We developed a triple-color Förster resonance energy transfer (3FRET) system to observe the dynamics of the formation of this trimolecular signaling complex in live human T cells and to follow the three molecular interactions in parallel. Using the 3FRET system, we demonstrated that dimers of Nck and Vav1 were constitutively formed independently of both T cell activation and the association between SLP-76 and Nck. After T cell receptor stimulation, SLP-76 was phosphorylated, which enabled the binding of Nck. A point mutation in the proline-rich site of Vav1, which abolishes its binding to Nck, impaired actin rearrangement, suggesting that Nck-Vav1 dimers play a critical role in regulation of the actin machinery. We suggest that these findings revise the accepted model of the formation of a complex of SLP-76, Nck, and Vav1 and demonstrate the use of 3FRET as a tool to study signal transduction in live cells.

Tunable Electron-Electron Interactions in LaAlO 3 / SrTiO 3 Nanostructures

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

Cheng, Guanglei; Tomczyk, Michelle; Tacla, Alexandre B.

The interface between the two complex oxides LaAlO 3 and SrTiO 3 has remarkable properties that can be locally reconfigured between conducting and insulating states using a conductive atomic force microscope. Prior investigations of “sketched” quantum dot devices revealed a phase in which electrons form pairs, implying a strongly attractive electron-electron interaction. Here, we show that these devices with strong electron-electron interactions can exhibit a gate-tunable transition from a pair-tunneling regime to a single-electron (Andreev bound state) tunneling regime where the interactions become repulsive. The electron-electron interaction sign change is associated with a Lifshitz transition where the d xz andmore » d yz bands start to become occupied. This electronically tunable electron-electron interaction, combined with the nanoscale reconfigurability of this system, provides an interesting starting point towards solid-state quantum simulation.« less

Tunable Electron-Electron Interactions in LaAlO 3 / SrTiO 3 Nanostructures

DOE PAGES

Cheng, Guanglei; Tomczyk, Michelle; Tacla, Alexandre B.; ...

2016-12-01

The interface between the two complex oxides LaAlO 3 and SrTiO 3 has remarkable properties that can be locally reconfigured between conducting and insulating states using a conductive atomic force microscope. Prior investigations of “sketched” quantum dot devices revealed a phase in which electrons form pairs, implying a strongly attractive electron-electron interaction. Here, we show that these devices with strong electron-electron interactions can exhibit a gate-tunable transition from a pair-tunneling regime to a single-electron (Andreev bound state) tunneling regime where the interactions become repulsive. The electron-electron interaction sign change is associated with a Lifshitz transition where the d xz andmore » d yz bands start to become occupied. This electronically tunable electron-electron interaction, combined with the nanoscale reconfigurability of this system, provides an interesting starting point towards solid-state quantum simulation.« less

Healthcare provider and patient perspectives on diagnostic imaging investigations.

PubMed

Makanjee, Chandra R; Bergh, Anne-Marie; Hoffmann, Willem A

2015-05-20

Much has been written about the patient-centred approach in doctor-patient consultations. Little is known about interactions and communication processes regarding healthcare providers' and patients' perspectives on expectations and experiences of diagnostic imaging investigations within the medical encounter. Patients journey through the health system from the point of referral to the imaging investigation itself and then to the post-imaging consultation. AIM AND SETTING: To explore healthcare provider and patient perspectives on interaction and communication processes during diagnostic imaging investigations as part of their clinical journey through a healthcare complex. A qualitative study was conducted, with two phases of data collection. Twenty-four patients were conveniently selected at a public district hospital complex and were followed throughout their journey in the hospital system, from admission to discharge. The second phase entailed focus group interviews conducted with providers in the district hospital and adjacent academic hospital (medical officers and family physicians, nurses, radiographers, radiology consultants and registrars). Two main themes guided our analysis: (1) provider perspectives; and (2) patient dispositions and reactions. Golden threads that cut across these themes are interactions and communication processes in the context of expectations, experiences of the imaging investigations and the outcomes thereof. Insights from this study provide a better understanding of the complexity of the processes and interactions between providers and patients during the imaging investigations conducted as part of their clinical pathway. The interactions and communication processes are provider-patient centred when a referral for a diagnostic imaging investigation is included.

RNA polymerase II trigger loop residues stabilize and position the incoming nucleotide triphosphate in transcription

PubMed Central

Huang, Xuhui; Wang, Dong; Weiss, Dahlia R.; Bushnell, David A.; Kornberg, Roger D.; Levitt, Michael

2010-01-01

A structurally conserved element, the trigger loop, has been suggested to play a key role in substrate selection and catalysis of RNA polymerase II (pol II) transcription elongation. Recently resolved X-ray structures showed that the trigger loop forms direct interactions with the β-phosphate and base of the matched nucleotide triphosphate (NTP) through residues His1085 and Leu1081, respectively. In order to understand the role of these two critical residues in stabilizing active site conformation in the dynamic complex, we performed all-atom molecular dynamics simulations of the wild-type pol II elongation complex and its mutants in explicit solvent. In the wild-type complex, we found that the trigger loop is stabilized in the “closed” conformation, and His1085 forms a stable interaction with the NTP. Simulations of point mutations of His1085 are shown to affect this interaction; simulations of alternative protonation states, which are inaccessible through experiment, indicate that only the protonated form is able to stabilize the His1085-NTP interaction. Another trigger loop residue, Leu1081, stabilizes the incoming nucleotide position through interaction with the nucleotide base. Our simulations of this Leu mutant suggest a three-component mechanism for correctly positioning the incoming NTP in which (i) hydrophobic contact through Leu1081, (ii) base stacking, and (iii) base pairing work together to minimize the motion of the incoming NTP base. These results complement experimental observations and provide insight into the role of the trigger loop on transcription fidelity. PMID:20798057

Aerosol Complexity and Implications for Predictability and Short-Term Forecasting

NASA Technical Reports Server (NTRS)

Colarco, Peter

2016-01-01

There are clear NWP and climate impacts from including aerosol radiative and cloud interactions. Changes in dynamics and cloud fields affect aerosol lifecycle, plume height, long-range transport, overall forcing of the climate system, etc. Inclusion of aerosols in NWP systems has benefit to surface field biases (e.g., T2m, U10m). Including aerosol affects has impact on analysis increments and can have statistically significant impacts on, e.g., tropical cyclogenesis. Above points are made especially with respect to aerosol radiative interactions, but aerosol-cloud interaction is a bigger signal on the global system. Many of these impacts are realized even in models with relatively simple (bulk) aerosol schemes (approx.10 -20 tracers). Simple schemes though imply simple representation of aerosol absorption and importantly for aerosol-cloud interaction particle-size distribution. Even so, more complex schemes exhibit a lot of diversity between different models, with issues such as size selection both for emitted particles and for modes. Prospects for complex sectional schemes to tune modal (and even bulk) schemes toward better selection of size representation. I think this is a ripe topic for more research -Systematic documentation of benefits of no vs. climatological vs. interactive (direct and then direct+indirect) aerosols. Document aerosol impact on analysis increments, inclusion in NWP data assimilation operator -Further refinement of baseline assumptions in model design (e.g., absorption, particle size distribution). Did not get into model resolution and interplay of other physical processes with aerosols (e.g., moist physics, obviously important), chemistry

Interaction of the Human Respiratory Syncytial Virus matrix protein with cellular adaptor protein complex 3 plays a critical role in trafficking.

PubMed

Ward, Casey; Maselko, Maciej; Lupfer, Christopher; Prescott, Meagan; Pastey, Manoj K

2017-01-01

Human Respiratory Syncytial Virus (HRSV) is a leading cause of bronchopneumonia in infants and the elderly. To date, knowledge of viral and host protein interactions within HRSV is limited and are critical areas of research. Here, we show that HRSV Matrix (M) protein interacts with the cellular adaptor protein complex 3 specifically via its medium subunit (AP-3Mu3A). This novel protein-protein interaction was first detected via yeast-two hybrid screen and was further confirmed in a mammalian system by immunofluorescence colocalization and co-immunoprecipitation. This novel interaction is further substantiated by the presence of a known tyrosine-based adaptor protein MU subunit sorting signal sequence, YXXФ: where Ф is a bulky hydrophobic residue, which is conserved across the related RSV M proteins. Analysis of point-mutated HRSV M derivatives indicated that AP-3Mu3A- mediated trafficking is contingent on the presence of the tyrosine residue within the YXXL sorting sequence at amino acids 197-200 of the M protein. AP-3Mu3A is up regulated at 24 hours post-infection in infected cells versus mock-infected HEp2 cells. Together, our data suggests that the AP-3 complex plays a critical role in the trafficking of HRSV proteins specifically matrix in epithelial cells. The results of this study add new insights and targets that may lead to the development of potential antivirals and attenuating mutations suitable for candidate vaccines in the future.

A stable transcription factor complex nucleated by oligomeric AML1–ETO controls leukaemogenesis

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

Sun, Xiao-Jian; Wang, Zhanxin; Wang, Lan

2013-06-30

Transcription factors are frequently altered in leukaemia through chromosomal translocation, mutation or aberrant expression. AML1–ETO, a fusion protein generated by the t(8;21) translocation in acute myeloid leukaemia, is a transcription factor implicated in both gene repression and activation. AML1–ETO oligomerization, mediated by the NHR2 domain, is critical for leukaemogenesis, making it important to identify co-regulatory factors that ‘read’ the NHR2 oligomerization and contribute to leukaemogenesis. Here we show that, in human leukaemic cells, AML1–ETO resides in and functions through a stable AML1–ETO-containing transcription factor complex (AETFC) that contains several haematopoietic transcription (co)factors. These AETFC components stabilize the complex through multivalentmore » interactions, provide multiple DNA-binding domains for diverse target genes, co-localize genome wide, cooperatively regulate gene expression, and contribute to leukaemogenesis. Within the AETFC complex, AML1–ETO oligomerization is required for a specific interaction between the oligomerized NHR2 domain and a novel NHR2-binding (N2B) motif in E proteins. Crystallographic analysis of the NHR2–N2B complex reveals a unique interaction pattern in which an N2B peptide makes direct contact with side chains of two NHR2 domains as a dimer, providing a novel model of how dimeric/oligomeric transcription factors create a new protein-binding interface through dimerization/oligomerization. Intriguingly, disruption of this interaction by point mutations abrogates AML1–ETO-induced haematopoietic stem/progenitor cell self-renewal and leukaemogenesis. These results reveal new mechanisms of action of AML1–ETO, and provide a potential therapeutic target in t(8;21)-positive acute myeloid leukaemia.« less

Data Visualization Using Immersive Virtual Reality Tools

NASA Astrophysics Data System (ADS)

Cioc, Alexandru; Djorgovski, S. G.; Donalek, C.; Lawler, E.; Sauer, F.; Longo, G.

2013-01-01

The growing complexity of scientific data poses serious challenges for an effective visualization. Data sets, e.g., catalogs of objects detected in sky surveys, can have a very high dimensionality, ~ 100 - 1000. Visualizing such hyper-dimensional data parameter spaces is essentially impossible, but there are ways of visualizing up to ~ 10 dimensions in a pseudo-3D display. We have been experimenting with the emerging technologies of immersive virtual reality (VR) as a platform for a scientific, interactive, collaborative data visualization. Our initial experiments used the virtual world of Second Life, and more recently VR worlds based on its open source code, OpenSimulator. There we can visualize up to ~ 100,000 data points in ~ 7 - 8 dimensions (3 spatial and others encoded as shapes, colors, sizes, etc.), in an immersive virtual space where scientists can interact with their data and with each other. We are now developing a more scalable visualization environment using the popular (practically an emerging standard) Unity 3D Game Engine, coded using C#, JavaScript, and the Unity Scripting Language. This visualization tool can be used through a standard web browser, or a standalone browser of its own. Rather than merely plotting data points, the application creates interactive three-dimensional objects of various shapes, colors, and sizes, and of course the XYZ positions, encoding various dimensions of the parameter space, that can be associated interactively. Multiple users can navigate through this data space simultaneously, either with their own, independent vantage points, or with a shared view. At this stage ~ 100,000 data points can be easily visualized within seconds on a simple laptop. The displayed data points can contain linked information; e.g., upon a clicking on a data point, a webpage with additional information can be rendered within the 3D world. A range of functionalities has been already deployed, and more are being added. We expect to make this visualization tool freely available to the academic community within a few months, on an experimental (beta testing) basis.

The Interaction of FABP with Kapα

PubMed Central

Amber-Vitos, Ortal; Kucherenko, Nataly; Nachliel, Esther; Gutman, Menachem; Tsfadia, Yossi

2015-01-01

Gene-activating lipophilic compounds are carried into the nucleus when loaded on fatty-acid-binding proteins (FABP). Some of these proteins are recognized by the α-Karyopherin (Kapα) through its nuclear localization signal (NLS) consisting of three positive residues that are not in a continuous sequence. The Importin system can distinguish between FABP loaded with activating and non-activating compounds. In the present study, we introduced molecular dynamics as a tool for clarifying the mechanism by which FABP4, loaded with activating ligand (linoleate) is recognized by Kapα. In the first phase, we simulated the complex between KapαΔIBB (termed “Armadillo”) that was crystallized with two NLS hepta-peptides. The trajectory revealed that the crystal-structure orientation of the peptides is rapidly lost and new interactions dominate. Though, the NLS sequence of FABP4 is cryptic, since the functional residues are not in direct sequence, implicating more than one possible conformation. Therefore, four possible docked conformations were generated, in which the NLS of FABP4 is interacting with either the major or the minor sites of Kapα, and the N → C vectors are parallel or anti-parallel. Out of these four basic starting positions, only the FABP4-minor site complex exhibited a large number of contact points. In this complex, the FABP interacts with the minor and the major sites, suppressing the self-inhibitory interaction of the Kapα, rendering it free to react with Kapβ. Finally, we propose that the transportable conformation generated an extended hydrophobic domain which expanded out of the boundary of the FABP4, allowing the loaded linoleate to partially migrate out of the FABP into a joint complex in which the Kapα contributes part of a combined binding pocket. PMID:26284534

Complex between triple helix of collagen and double helix of DNA in aqueous solution.

PubMed

Mrevlishvili, George M; Svintradze, David V

2005-06-01

We demonstrate in this paper that one example of a biologically important and molecular self-assembling complex system is a collagen-DNA ordered aggregate which spontaneously forms in aqueous solutions. Interaction between the collagen and the DNA leads to destruction of the hydration shell of the triple helix and stabilization of the double helix structure. From a molecular biology point of view this nano-scale self-assembling superstructure could increase the stability of DNA against the nucleases during collagen diseases and the growth of collagen fibrills in the presence of DNA.

Guided solitary waves.

PubMed

Miles, J

1980-04-01

Transversely periodic solitary-wave solutions of the Boussinesq equations (which govern wave propagation in a weakly dispersive, weakly nonlinear physical system) are determined. The solutions for negative dispersion (e.g., gravity waves) are singular and therefore physically unacceptable. The solutions for positive dispersion (e.g., capillary waves or magnetosonic waves in a plasma) are physically acceptable except in a limited parametric interval, in which they are complex. The two end points of this interval are associated with (two different) resonant interactions among three basic solitary waves, two of which are two-dimensional complex conjugates and the third of which is one-dimensional and real.

Looking for Broken TAD Boundaries and Changes on DNA Interactions: Clinical Guide to 3D Chromatin Change Analysis in Complex Chromosomal Rearrangements and Chromothripsis.

PubMed

Yauy, Kevin; Gatinois, Vincent; Guignard, Thomas; Sati, Satish; Puechberty, Jacques; Gaillard, Jean Baptiste; Schneider, Anouck; Pellestor, Franck

2018-01-01

Apparition of next-generation sequencing (NGS) was a breakthrough on knowledge of genome structure. Bioinformatic tools are a key point to analyze this huge amount of data from NGS and characterize the three-dimensional organization of chromosomes. This chapter describes usage of different browsers to explore publicly available online data and to search for possible 3D chromatin changes involved during complex chromosomal rearrangements as chromothripsis. Their pathogenic impact on clinical phenotype and gene misexpression can also be evaluated with annotated databases.

Class-first analysis in a continuum: an approach to the complexities of schools, society, and insurgent science

NASA Astrophysics Data System (ADS)

Valdiviezo, Laura Alicia

2010-06-01

This essay addresses Katherine Richardson Bruna's paper: Mexican Immigrant Transnational Social Capital and Class Transformation: Examining the Role of Peer Mediation in Insurgent Science, through five main points . First, I offer a comparison between the traditional analysis of classism in Latin America and Richardson Bruna's call for a class-first analysis in the North American social sciences where there has been a tendency to obviate the specific examination of class relations and class issues. Secondly, I discuss that a class-first analysis solely cannot suffice to depict the complex dimensions in the relations of schools and society. Thus, I suggest a continuum in the class-first analysis. Third, I argue that social constructions surrounding issues of language, ethnicity, and gender necessarily intersect with issues of class and that, in fact, those other constructions offer compatible epistemologies that aid in representing the complexity of social and institutional practices in the capitalist society. Richardson Bruna's analysis of Augusto's interactions with his teacher and peers in the science class provides a fourth point of discussion in this essay. As a final point in my response I discuss Richardson Bruna's idea of making accessible class-first analysis knowledge to educators and especially to science teachers.

The Weight of English in Global Perspective: The Role of English in Israel

ERIC Educational Resources Information Center

Shohamy, Elana

2014-01-01

The aim of this chapter is to point to the complexities of the English language in Israel from a critical perspective, its global language status, and the manners in which it affects and interacts with a variety of local issues. The main focus is on how the presence of a global language, like English, affects a given sociolinguistic reality,…

Serving the Cause: Duty Concepts and Combat Effectiveness in War

DTIC Science & Technology

2010-06-01

War II.10 Like moral factors, the notion of military effectiveness is complex and multi-faceted. Murray and Millet argue that military...The insights derived from this synthesis will provide the common reference point for analysis of the historical examples. Alan Millet and...1988). 4 Allan Millet and Williamson Murray, Military Effectiveness, Vol I, 2. 9 This dynamic interaction is particularly pronounced at the

Integrating the invisible fabric of nature into fisheries management.

PubMed

Travis, Joseph; Coleman, Felicia C; Auster, Peter J; Cury, Philippe M; Estes, James A; Orensanz, Jose; Peterson, Charles H; Power, Mary E; Steneck, Robert S; Wootton, J Timothy

2014-01-14

Overfishing and environmental change have triggered many severe and unexpected consequences. As existing communities have collapsed, new ones have become established, fundamentally transforming ecosystems to those that are often less productive for fisheries, more prone to cycles of booms and busts, and thus less manageable. We contend that the failure of fisheries science and management to anticipate these transformations results from a lack of appreciation for the nature, strength, complexity, and outcome of species interactions. Ecologists have come to understand that networks of interacting species exhibit nonlinear dynamics and feedback loops that can produce sudden and unexpected shifts. We argue that fisheries science and management must follow this lead by developing a sharper focus on species interactions and how disrupting these interactions can push ecosystems in which fisheries are embedded past their tipping points.

An experimental and theoretical study of a hydrogen-bonded complex: O-phenylenediamine with 2,6-pyridinedicarboxylic acid

NASA Astrophysics Data System (ADS)

Ghasemi, Khaled; Rezvani, Ali Reza; Habibi-Khorassani, Sayyed Mostafa; Shahraki, Mehdi; Shokrollahi, Ardeshir; Moghimi, Abolghasem; Tamandani, Halimeh Kord; Gavahi, Sara

2015-11-01

The hydrogen-bonded complex, [(OPDH)+(dipicH)-.H2O], between o-phenylenediamine (OPD) and 2,6-pyridinedicarboxylic acid (dipicH2) has been characterized in water by the 1H, 13C NMR and IR spectroscopies. The crystal structure showed that the edge to face C-H⋯π and C-O⋯π stacking interactions between the dipicH2 and OPD rings play an extra significant role in the formation of the hydrogen-bonded complex and supported the H-bonding interactions. The proton transfer also investigated theoretically in gas phase and thermodynamic parameters such as ΔH‡, ΔG‡, ΔS‡ were calculated for this process. Moreover, intramolecular hydrogen-bonding interaction has been recognized by calculating the electron density ρ(r) and Laplacian ∇2ρ(r) at the bond critical point (BCP) using Atoms-In-Molecule (AIM) method and also the interaction between electron acceptor (σ*) of OH with the lone pair of the nitrogen atom as an electron donor using Natural Bond Orbital (NBO) analysis. In addition, the protonation constants of dipicH2 and OPD and the equilibrium constants for the dipic-OPD (1:1) proton transfer system were obtained by the potentiometric pH titration method using the Hyperquad 2008 program. The stoichiometry of the proton transfer species in the solution confirmed the solid state result.

Interactive orbital proximity operations planning system

NASA Technical Reports Server (NTRS)

Grunwald, Arthur J.; Ellis, Stephen R.

1989-01-01

An interactive, graphical proximity operations planning system was developed which allows on-site design of efficient, complex, multiburn maneuvers in the dynamic multispacecraft environment about the space station. Maneuvering takes place in, as well as out of, the orbital plane. The difficulty in planning such missions results from the unusual and counterintuitive character of relative orbital motion trajectories and complex operational constraints, which are both time varying and highly dependent on the mission scenario. This difficulty is greatly overcome by visualizing the relative trajectories and the relative constraints in an easily interpretable, graphical format, which provides the operator with immediate feedback on design actions. The display shows a perspective bird's-eye view of the space station and co-orbiting spacecraft on the background of the station's orbital plane. The operator has control over two modes of operation: (1) a viewing system mode, which enables him or her to explore the spatial situation about the space station and thus choose and frame in on areas of interest; and (2) a trajectory design mode, which allows the interactive editing of a series of way-points and maneuvering burns to obtain a trajectory which complies with all operational constraints. Through a graphical interactive process, the operator will continue to modify the trajectory design until all operational constraints are met. The effectiveness of this display format in complex trajectory design is presently being evaluated in an ongoing experimental program.

Control system design and analysis using the INteractive Controls Analysis (INCA) program

NASA Technical Reports Server (NTRS)

Bauer, Frank H.; Downing, John P.

1987-01-01

The INteractive Controls Analysis (INCA) program was developed at the Goddard Space Flight Center to provide a user friendly efficient environment for the design and analysis of linear control systems. Since its inception, INCA has found extensive use in the design, development, and analysis of control systems for spacecraft, instruments, robotics, and pointing systems. Moreover, the results of the analytic tools imbedded in INCA have been flight proven with at least three currently orbiting spacecraft. This paper describes the INCA program and illustrates, using a flight proven example, how the package can perform complex design analyses with relative ease.

Absence of first-order unbinding transitions of fluid and polymerized membranes

NASA Technical Reports Server (NTRS)

Grotehans, Stefan; Lipowsky, Reinhard

1990-01-01

Unbinding transitions of fluid and polymerized membranes are studied by renormalization-group (RG) methods. Two different RG schemes are used and found to give rather consistent results. The fixed-point structure of both RG's exhibits a complex behavior as a function of the decay exponent tau for the fluctuation-induced interaction of the membranes. For tau greater than tau(S2) interacting membranes can undergo first-order transitions even in the strong-fluctuation regime. These estimates for tau(S2) imply, however, that both fluid and polymerized membranes unbind in a continuous way in the absence of lateral tension.

Potentiometric Determination of Phytic Acid and Investigations of Phytate Interactions with Some Metal Ions.

PubMed

Marolt, Gregor; Pihlar, Boris

2015-01-01

Determination of correct amount (concentration) of phytic acid is of vital importance when dealing with protonation and/or metal complexation equilibria. A novel approach for precise and reliable assay of phytic acid, based on the difference between end points by potentiometric titration, has been presented. Twelve phytic acid protons are classified into three groups of acidity, which enables detection of 2 to 3 distinct equivalent points (EPs) depending on experimental conditions, e.g. counter-ion concentration. Using the differences between individual EPs enables correct phytate determination as well as identification of potential contamination and/or determination of initial protonation degree. Impact of uncertainty of phytate amount on the calculation of protonation constants has been evaluated using computer simulation program (Hyperquad2013). With the analysis of titration curves different binding sites on phytate ligand have been proposed for complexation of Ca2+ and Fe3+ ions.

Complex Dynamics of Wetland Ecosystem with Nonlinear Harvesting: Application to Chilika Lake in Odisha, India

NASA Astrophysics Data System (ADS)

Upadhyay, Ranjit Kumar; Tiwari, S. K.; Roy, Parimita

2015-06-01

In this paper, an attempt has been made to study the spatial and temporal dynamical interactions among the species of wetland ecosystem through a mathematical model. The model represents the population dynamics of phytoplankton, zooplankton and fish species found in Chilika lake, Odisha, India. Nonlinear stability analysis of both the temporal and spatial models has been carried out. Maximum sustainable yield and optimal harvesting policy have been studied for a nonspatial model system. Numerical simulation has been performed to figure out the parameters responsible for the complex dynamics of the wetland system. Significant outcomes of our numerical findings and their interpretations from an ecological point of view are provided in this paper. Numerical simulation of spatial model exhibits some interesting and beautiful patterns. We have also pointed out the parameters that are responsible for the good health of wetland ecosystem.

Active vibration suppression of helicopter horizontal stabilizers

NASA Astrophysics Data System (ADS)

Cinquemani, Simone; Cazzulani, Gabriele; Resta, Ferruccio

2017-04-01

Helicopters are among the most complex machines ever made. While ensuring high performance from the aeronautical point of view, they are not very comfortable due to vibration mainly created by the main rotor and by the interaction with the surrounding air. One of the most solicited structural elements of the vehicle are the horizontal stabilizers. These elements are particularly stressed because of their composite structure which, while guaranteeing lightness and strength, is characterized by a low damping. This work makes a preliminary analysis on the dynamics of the structure and proposes different solutions to actively suppress vibrations. Among them, the best in terms of the relationship between performance and weight / complexity of the system is that based on inertial actuators mounted on the inside of the horizontal stabilizers. The work addresses the issue of the design of the device and its use in the stabilizer from both the numerical and the experimental points of view.

Virtual interactive presence for real-time, long-distance surgical collaboration during complex microsurgical procedures.

PubMed

Shenai, Mahesh B; Tubbs, R Shane; Guthrie, Barton L; Cohen-Gadol, Aaron A

2014-08-01

The shortage of surgeons compels the development of novel technologies that geographically extend the capabilities of individual surgeons and enhance surgical skills. The authors have developed "Virtual Interactive Presence" (VIP), a platform that allows remote participants to simultaneously view each other's visual field, creating a shared field of view for real-time surgical telecollaboration. The authors demonstrate the capability of VIP to facilitate long-distance telecollaboration during cadaveric dissection. Virtual Interactive Presence consists of local and remote workstations with integrated video capture devices and video displays. Each workstation mutually connects via commercial teleconferencing devices, allowing worldwide point-to-point communication. Software composites the local and remote video feeds, displaying a hybrid perspective to each participant. For demonstration, local and remote VIP stations were situated in Indianapolis, Indiana, and Birmingham, Alabama, respectively. A suboccipital craniotomy and microsurgical dissection of the pineal region was performed in a cadaveric specimen using VIP. Task and system performance were subjectively evaluated, while additional video analysis was used for objective assessment of delay and resolution. Participants at both stations were able to visually and verbally interact while identifying anatomical structures, guiding surgical maneuvers, and discussing overall surgical strategy. Video analysis of 3 separate video clips yielded a mean compositing delay of 760 ± 606 msec (when compared with the audio signal). Image resolution was adequate to visualize complex intracranial anatomy and provide interactive guidance. Virtual Interactive Presence is a feasible paradigm for real-time, long-distance surgical telecollaboration. Delay, resolution, scaling, and registration are parameters that require further optimization, but are within the realm of current technology. The paradigm potentially enables remotely located experts to mentor less experienced personnel located at the surgical site with applications in surgical training programs, remote proctoring for proficiency, and expert support for rural settings and across different counties.

Children with migraine: Provocation of headache via pressure to myofascial trigger points in the trapezius muscle? - A prospective controlled observational study.

PubMed

Landgraf, M N; Biebl, J T; Langhagen, T; Hannibal, I; Eggert, T; Vill, K; Gerstl, L; Albers, L; von Kries, R; Straube, A; Heinen, F

2018-02-01

The objective was to evaluate a supposed clinical interdependency of myofascial trigger points and migraine in children. Such interdependency would support an interaction of spinal and trigeminal afferences in the trigemino-cervical complex as a contributing factor in migraine. Children ≤18 years with the confirmed diagnosis of migraine were prospectively investigated. Comprehensive data on medical history, clinical neurological and psychological status were gathered. Trigger points in the trapezius muscle were identified by palpation and the threshold of pressure pain at these points was measured. Manual pressure was applied to the trigger points, and the occurrence and duration of induced headache were recorded. At a second consultation (4 weeks after the first), manual pressure with the detected pressure threshold was applied to non-trigger points within the same trapezius muscle (control). Headache and related parameters were again recorded and compared to the results of the first consultation. A total of 13 girls and 13 boys with migraine and a median age of 14.5 (Range 6.3-17.8) years took part in the study. Manual pressure to trigger points in the trapezius muscle led to lasting headache after termination of the manual pressure in 13 patients while no patient experienced headache when manual pressure was applied to non-trigger points at the control visit (p < 0.001). Headache was induced significantly more often in children ≥12 years and those with internalizing behavioural disorder. We found an association between trapezius muscle myofascial trigger points and migraine, which might underline the concept of the trigemino-cervical complex, especially in adolescents. In children with migraine headache can often be induced by pressure to myofascial trigger points, but not by pressure to non-trigger points in the trapezius muscle. This supports the hypothesis of a trigemino-cervical-complex in the pathophysiology of migraine, which might have implications for innovative therapies in children with migraine. © 2017 European Pain Federation - EFIC®.

Control-structure interaction study for the Space Station solar dynamic power module

NASA Technical Reports Server (NTRS)

Cheng, J.; Ianculescu, G.; Ly, J.; Kim, M.

1991-01-01

The authors investigate the feasibility of using a conventional PID (proportional plus integral plus derivative) controller design to perform the pointing and tracking functions for the Space Station Freedom solar dynamic power module. Using this simple controller design, the control/structure interaction effects were also studied without assuming frequency bandwidth separation. From the results, the feasibility of a simple solar dynamic control solution with a reduced-order model, which satisfies the basic system pointing and stability requirements, is suggested. However, the conventional control design approach is shown to be very much influenced by the order of reduction of the plant model, i.e., the number of the retained elastic modes from the full-order model. This suggests that, for complex large space structures, such as the Space Station Freedom solar dynamic, the conventional control system design methods may not be adequate.

Comparison of 3D ion velocity distribution measurements and models in the vicinity of an absorbing boundary oriented obliquely to a magnetic field

NASA Astrophysics Data System (ADS)

Henriquez, Miguel F.; Thompson, Derek S.; Kenily, Shane; Khaziev, Rinat; Good, Timothy N.; McIlvain, Julianne; Siddiqui, M. Umair; Curreli, Davide; Scime, Earl E.

2016-10-01

Understanding particle distributions in plasma boundary regions is critical to predicting plasma-surface interactions. Ions in the presheath exhibit complex behavior because of collisions and due to the presence of boundary-localized electric fields. Complete understanding of particle dynamics is necessary for understanding the critical problems of tokamak wall loading and Hall thruster channel wall erosion. We report measurements of 3D argon ion velocity distribution functions (IVDFs) in the vicinity of an absorbing boundary oriented obliquely to a background magnetic field. Measurements were obtained via argon ion laser induced fluorescence throughout a spatial volume upstream of the boundary. These distribution functions reveal kinetic details that provide a point-to-point check on particle-in-cell and 1D3V Boltzmann simulations. We present the results of this comparison and discuss some implications for plasma boundary interaction physics.

Science diplomacy: Investigating the perspective of scholars on politics-science collaboration in international affairs.

PubMed

Fähnrich, Birte

2017-08-01

Science diplomacy is a widely practiced area of international affairs, but academic research is rather sparse. The role of academia within this field of politics-science interaction has hardly been considered. This article analyzes this scholarly perspective: Based on a literature review, a case study of a German science diplomacy program is used to explore objectives, benefits, and constraints of science diplomacy for participating scholars. While political approaches suggest an ideal world where both sides profit from the collaboration, the findings of the case study point to another conclusion which shows that the interaction of scholars and officials in science diplomacy is far more complex. Thus, the contribution is regarded as both a useful starting point for further research and for a critical reflection of academics and politicians in science diplomacy practice to gauge what can be expected from the collaboration and what cannot.

Analysis and application of opinion model with multiple topic interactions.

PubMed

Xiong, Fei; Liu, Yun; Wang, Liang; Wang, Ximeng

2017-08-01

To reveal heterogeneous behaviors of opinion evolution in different scenarios, we propose an opinion model with topic interactions. Individual opinions and topic features are represented by a multidimensional vector. We measure an agent's action towards a specific topic by the product of opinion and topic feature. When pairs of agents interact for a topic, their actions are introduced to opinion updates with bounded confidence. Simulation results show that a transition from a disordered state to a consensus state occurs at a critical point of the tolerance threshold, which depends on the opinion dimension. The critical point increases as the dimension of opinions increases. Multiple topics promote opinion interactions and lead to the formation of macroscopic opinion clusters. In addition, more topics accelerate the evolutionary process and weaken the effect of network topology. We use two sets of large-scale real data to evaluate the model, and the results prove its effectiveness in characterizing a real evolutionary process. Our model achieves high performance in individual action prediction and even outperforms state-of-the-art methods. Meanwhile, our model has much smaller computational complexity. This paper provides a demonstration for possible practical applications of theoretical opinion dynamics.

Interactions of Aspergillus fumigatus Conidia with Airway Epithelial Cells: A Critical Review

PubMed Central

Croft, Carys A.; Culibrk, Luka; Moore, Margo M.; Tebbutt, Scott J.

2016-01-01

Aspergillus fumigatus is an environmental filamentous fungus that also acts as an opportunistic pathogen able to cause a variety of symptoms, from an allergic response to a life-threatening disseminated fungal infection. The infectious agents are inhaled conidia whose first point of contact is most likely to be an airway epithelial cell (AEC). The interaction between epithelial cells and conidia is multifaceted and complex, and has implications for later steps in pathogenesis. Increasing evidence has demonstrated a key role for the airway epithelium in the response to respiratory pathogens, particularly at early stages of infection; therefore, elucidating the early stages of interaction of conidia with AECs is essential to understand the establishment of infection in cohorts of at-risk patients. Here, we present a comprehensive review of the early interactions between A. fumigatus and AECs, including bronchial and alveolar epithelial cells. We describe mechanisms of adhesion, internalization of conidia by AECs, the immune response of AECs, as well as the role of fungal virulence factors, and patterns of fungal gene expression characteristic of early infection. A clear understanding of the mechanisms involved in the early establishment of infection by A. fumigatus could point to novel targets for therapy and prophylaxis. PMID:27092126

Identifying Ant-Mirid Spatial Interactions to Improve Biological Control in Cacao-Based Agroforestry System.

PubMed

Bagny Beilhe, Leïla; Piou, Cyril; Tadu, Zéphirin; Babin, Régis

2018-06-06

The use of ants for biological control of insect pests was the first reported case of conservation biological control. Direct and indirect community interactions between ants and pests lead to differential spatial pattern. We investigated spatial interactions between mirids, the major cocoa pest in West Africa and numerically dominant ant species, using bivariate point pattern analysis to identify potential biological control agents. We assume that potential biological control agents should display negative spatial interactions with mirids considering their niche overlap. The mirid/ant data were collected in complex cacao-based agroforestry systems sampled in three agroecological areas over a forest-savannah gradient in Cameroon. Three species, Crematogaster striatula Emery (Hymenoptera: Formicidae), Crematogaster clariventris Mayr (Hymenoptera: Formicidae), and Oecophylla longinoda Latreille (Hymenoptera: Formicidae) with high predator and aggressive behaviors were identified as dominant and showed negative spatial relationships with mirids. The weaver ant, O. longinoda was identified as the only potential biological control agent, considering its ubiquity in the plots, the similarity in niche requirements, and the spatial segregation with mirids resulting probably from exclusion mechanisms. Combining bivariate point pattern analysis to good knowledge of insect ecology was an effective method to identify a potentially good biological control agent.

Structure of the dimeric exonuclease TREX1 in complex with DNA displays a proline-rich binding site for WW Domains.

PubMed

Brucet, Marina; Querol-Audí, Jordi; Serra, Maria; Ramirez-Espain, Ximena; Bertlik, Kamila; Ruiz, Lidia; Lloberas, Jorge; Macias, Maria J; Fita, Ignacio; Celada, Antonio

2007-05-11

TREX1 is the most abundant mammalian 3' --> 5' DNA exonuclease. It has been described to form part of the SET complex and is responsible for the Aicardi-Goutières syndrome in humans. Here we show that the exonuclease activity is correlated to the binding preferences toward certain DNA sequences. In particular, we have found three motifs that are selected, GAG, ACA, and CTGC. To elucidate how the discrimination occurs, we determined the crystal structures of two murine TREX1 complexes, with a nucleotide product of the exonuclease reaction, and with a single-stranded DNA substrate. Using confocal microscopy, we observed TREX1 both in nuclear and cytoplasmic subcellular compartments. Remarkably, the presence of TREX1 in the nucleus requires the loss of a C-terminal segment, which we named leucine-rich repeat 3. Furthermore, we detected the presence of a conserved proline-rich region on the surface of TREX1. This observation points to interactions with proline-binding domains. The potential interacting motif "PPPVPRPP" does not contain aromatic residues and thus resembles other sequences that select SH3 and/or Group 2 WW domains. By means of nuclear magnetic resonance titration experiments, we show that, indeed, a polyproline peptide derived from the murine TREX1 sequence interacted with the WW2 domain of the elongation transcription factor CA150. Co-immunoprecipitation studies confirmed this interaction with the full-length TREX1 protein, thereby suggesting that TREX1 participates in more functional complexes than previously thought.

Hepatitis C Virus Proteins Interact with the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery via Ubiquitination To Facilitate Viral Envelopment.

PubMed

Barouch-Bentov, Rina; Neveu, Gregory; Xiao, Fei; Beer, Melanie; Bekerman, Elena; Schor, Stanford; Campbell, Joseph; Boonyaratanakornkit, Jim; Lindenbach, Brett; Lu, Albert; Jacob, Yves; Einav, Shirit

2016-11-01

Enveloped viruses commonly utilize late-domain motifs, sometimes cooperatively with ubiquitin, to hijack the endosomal sorting complex required for transport (ESCRT) machinery for budding at the plasma membrane. However, the mechanisms underlying budding of viruses lacking defined late-domain motifs and budding into intracellular compartments are poorly characterized. Here, we map a network of hepatitis C virus (HCV) protein interactions with the ESCRT machinery using a mammalian-cell-based protein interaction screen and reveal nine novel interactions. We identify HRS (hepatocyte growth factor-regulated tyrosine kinase substrate), an ESCRT-0 complex component, as an important entry point for HCV into the ESCRT pathway and validate its interactions with the HCV nonstructural (NS) proteins NS2 and NS5A in HCV-infected cells. Infectivity assays indicate that HRS is an important factor for efficient HCV assembly. Specifically, by integrating capsid oligomerization assays, biophysical analysis of intracellular viral particles by continuous gradient centrifugations, proteolytic digestion protection, and RNase digestion protection assays, we show that HCV co-opts HRS to mediate a late assembly step, namely, envelopment. In the absence of defined late-domain motifs, K63-linked polyubiquitinated lysine residues in the HCV NS2 protein bind the HRS ubiquitin-interacting motif to facilitate assembly. Finally, ESCRT-III and VPS/VTA1 components are also recruited by HCV proteins to mediate assembly. These data uncover involvement of ESCRT proteins in intracellular budding of a virus lacking defined late-domain motifs and a novel mechanism by which HCV gains entry into the ESCRT network, with potential implications for other viruses. Viruses commonly bud at the plasma membrane by recruiting the host ESCRT machinery via conserved motifs termed late domains. The mechanism by which some viruses, such as HCV, bud intracellularly is, however, poorly characterized. Moreover, whether envelopment of HCV and other viruses lacking defined late domains is ESCRT mediated and, if so, what the entry points into the ESCRT pathway are remain unknown. Here, we report the interaction network of HCV with the ESCRT machinery and a critical role for HRS, an ESCRT-0 complex component, in HCV envelopment. Viral protein ubiquitination was discovered to be a signal for HRS binding and HCV assembly, thereby functionally compensating for the absence of late domains. These findings characterize how a virus lacking defined late domains co-opts ESCRT to bud intracellularly. Since the ESCRT machinery is essential for the life cycle of multiple viruses, better understanding of this virus-host interplay may yield targets for broad-spectrum antiviral therapies. Copyright © 2016 Barouch-Bentov et al.

CarD uses a minor groove wedge mechanism to stabilize the RNA polymerase open promoter complex.

PubMed

Bae, Brian; Chen, James; Davis, Elizabeth; Leon, Katherine; Darst, Seth A; Campbell, Elizabeth A

2015-09-08

A key point to regulate gene expression is at transcription initiation, and activators play a major role. CarD, an essential activator in Mycobacterium tuberculosis, is found in many bacteria, including Thermus species, but absent in Escherichia coli. To delineate the molecular mechanism of CarD, we determined crystal structures of Thermus transcription initiation complexes containing CarD. The structures show CarD interacts with the unique DNA topology presented by the upstream double-stranded/single-stranded DNA junction of the transcription bubble. We confirm that our structures correspond to functional activation complexes, and extend our understanding of the role of a conserved CarD Trp residue that serves as a minor groove wedge, preventing collapse of the transcription bubble to stabilize the transcription initiation complex. Unlike E. coli RNAP, many bacterial RNAPs form unstable promoter complexes, explaining the need for CarD.

The Proteomic Profile of Deleted in Breast Cancer 1 (DBC1) Interactions Points to a Multifaceted Regulation of Gene Expression*

PubMed Central

Giguère, Sophie S. B.; Guise, Amanda J.; Jean Beltran, Pierre M.; Joshi, Preeti M.; Greco, Todd M.; Quach, Olivia L.; Kong, Jeffery; Cristea, Ileana M.

2016-01-01

Deleted in breast cancer 1 (DBC1) has emerged as an important regulator of multiple cellular processes, ranging from gene expression to cell cycle progression. DBC1 has been linked to tumorigenesis both as an inhibitor of histone deacetylases, HDAC3 and sirtuin 1, and as a transcriptional cofactor for nuclear hormone receptors. However, despite mounting interest in DBC1, relatively little is known about the range of its interacting partners and the scope of its functions. Here, we carried out a functional proteomics-based investigation of DBC1 interactions in two relevant cell types, T cells and kidney cells. Microscopy, molecular biology, biochemistry, and mass spectrometry studies allowed us to assess DBC1 mRNA and protein levels, localization, phosphorylation status, and protein interaction networks. The comparison of DBC1 interactions in these cell types revealed conserved regulatory roles for DBC1 in gene expression, chromatin organization and modification, and cell cycle progression. Interestingly, we observe previously unrecognized DBC1 interactions with proteins encoded by cancer-associated genes. Among these interactions are five components of the SWI/SNF complex, the most frequently mutated chromatin remodeling complex in human cancers. Additionally, we identified a DBC1 interaction with TBL1XR1, a component of the NCoR complex, which we validated by reciprocal isolation. Strikingly, we discovered that DBC1 associates with proteins that regulate the circadian cycle, including DDX5, DHX9, and SFPQ. We validated this interaction by colocalization and reciprocal isolation. Functional assessment of this association demonstrated that DBC1 protein levels are important for regulating CLOCK and BMAL1 protein oscillations in synchronized T cells. Our results suggest that DBC1 is integral to the maintenance of the circadian molecular clock. Furthermore, the identified interactions provide a valuable resource for the exploration of pathways involved in DBC1-associated tumorigenesis. PMID:26657080

Redefining the endophenotype concept to accommodate transdiagnostic vulnerabilities and etiological complexity.

PubMed

Beauchaine, Theodore P; Constantino, John N

2017-09-11

In psychopathology research, endophenotypes are a subset of biomarkers that indicate genetic vulnerability independent of clinical state. To date, an explicit expectation is that endophenotypes be specific to single disorders. We evaluate this expectation considering recent advances in psychiatric genetics, recognition that transdiagnostic vulnerability traits are often more useful than clinical diagnoses in psychiatric genetics, and appreciation for etiological complexity across genetic, neural, hormonal and environmental levels of analysis. We suggest that the disorder-specificity requirement of endophenotypes be relaxed, that neural functions are preferable to behaviors as starting points in searches for endophenotypes, and that future research should focus on interactive effects of multiple endophenotypes on complex psychiatric disorders, some of which are 'phenocopies' with distinct etiologies.

Hydrogen bonding assemblies in host guest complexes with 18-crown-6

NASA Astrophysics Data System (ADS)

Fonari, M. S.; Simonov, Yu. A.; Kravtsov, V. Ch.; Lipkowski, J.; Ganin, E. V.; Yavolovskii, A. A.

2003-02-01

Recent X-ray crystal structural data for two novel 1:2 host-guest complexes of 18-crown-6 with neutral organic molecules, thiaamide hydrazide of 2-aminobenzoic acid and thiaamide hydrazide of 4-amino-1,2,5-thiadiazole-3-carbonic acid are reported. The supramolecular structures of these two and five relative complexes are discussed from the point of view of participation of donor groups in coordination with the crown ether, and donor and acceptor groups in the self-assembly of the guest molecules. Guest molecules have incorporated amine and hydrazine moieties as proton donors and carbonyl oxygen and sulfur (in thiadiazole and in thiaamine moieties) as proton acceptors. The guest-guest interactions appeared to be crucial in the final architecture.

The dynamic relationship between cerebellar Purkinje cell simple spikes and the spikelet number of complex spikes

PubMed Central

Burroughs, Amelia; Wise, Andrew K.; Xiao, Jianqiang; Houghton, Conor; Tang, Tianyu; Suh, Colleen Y.; Lang, Eric J.

2016-01-01

Key points Purkinje cells are the sole output of the cerebellar cortex and fire two distinct types of action potential: simple spikes and complex spikes.Previous studies have mainly considered complex spikes as unitary events, even though the waveform is composed of varying numbers of spikelets.The extent to which differences in spikelet number affect simple spike activity (and vice versa) remains unclear.We found that complex spikes with greater numbers of spikelets are preceded by higher simple spike firing rates but, following the complex spike, simple spikes are reduced in a manner that is graded with spikelet number.This dynamic interaction has important implications for cerebellar information processing, and suggests that complex spike spikelet number may maintain Purkinje cells within their operational range. Abstract Purkinje cells are central to cerebellar function because they form the sole output of the cerebellar cortex. They exhibit two distinct types of action potential: simple spikes and complex spikes. It is widely accepted that interaction between these two types of impulse is central to cerebellar cortical information processing. Previous investigations of the interactions between simple spikes and complex spikes have mainly considered complex spikes as unitary events. However, complex spikes are composed of an initial large spike followed by a number of secondary components, termed spikelets. The number of spikelets within individual complex spikes is highly variable and the extent to which differences in complex spike spikelet number affects simple spike activity (and vice versa) remains poorly understood. In anaesthetized adult rats, we have found that Purkinje cells recorded from the posterior lobe vermis and hemisphere have high simple spike firing frequencies that precede complex spikes with greater numbers of spikelets. This finding was also evident in a small sample of Purkinje cells recorded from the posterior lobe hemisphere in awake cats. In addition, complex spikes with a greater number of spikelets were associated with a subsequent reduction in simple spike firing rate. We therefore suggest that one important function of spikelets is the modulation of Purkinje cell simple spike firing frequency, which has implications for controlling cerebellar cortical output and motor learning. PMID:27265808

Adsorption of Selenium and Strontium on Goethite: EXAFS Study and Surface Complexation Modeling of the Ternary Systems.

PubMed

Nie, Zhe; Finck, Nicolas; Heberling, Frank; Pruessmann, Tim; Liu, Chunli; Lützenkirchen, Johannes

2017-04-04

Knowledge of the geochemical behavior of selenium and strontium is critical for the safe disposal of radioactive wastes. Goethite, as one of the most thermodynamically stable and commonly occurring natural iron oxy-hydroxides, promisingly retains these elements. This work comprehensively studies the adsorption of Se(IV) and Sr(II) on goethite. Starting from electrokinetic measurements, the binary and ternary adsorption systems are investigated and systematically compared via batch experiments, EXAFS analysis, and CD-MUSIC modeling. Se(IV) forms bidentate inner-sphere surface complexes, while Sr(II) is assumed to form outer-sphere complexes at low and intermediate pH and inner-sphere complexes at high pH. Instead of a direct interaction between Se(IV) and Sr(II), our results indicate an electrostatically driven mutual enhancement of adsorption. Adsorption of Sr(II) is promoted by an average factor of 5 within the typical groundwater pH range from 6 to 8 for the concentration range studied here. However, the interaction between Se(IV) and Sr(II) at the surface is two-sided, Se(IV) promotes Sr(II) outer-sphere adsorption, but competes for inner-sphere adsorption sites at high pH. The complexity of surfaces is highlighted by the inability of adsorption models to predict isoelectric points without additional constraints.

The Thermodynamics of Anion Complexation to Nonpolar Pockets.

PubMed

Sullivan, Matthew R; Yao, Wei; Tang, Du; Ashbaugh, Henry S; Gibb, Bruce C

2018-02-08

The interactions between nonpolar surfaces and polarizable anions lie in a gray area between the hydrophobic and Hofmeister effects. To assess the affinity of these interactions, NMR and ITC were used to probe the thermodynamics of eight anions binding to four different hosts whose pockets each consist primarily of hydrocarbon. Two classes of host were examined: cavitands and cyclodextrins. For all hosts, anion affinity was found to follow the Hofmeister series, with associations ranging from 1.6-5.7 kcal mol -1 . Despite the fact that cavitand hosts 1 and 2 possess intrinsic negative electrostatic fields, it was determined that these more enveloping hosts generally bound anions more strongly. The observation that the four hosts each possess specific anion affinities that cannot be readily explained by their structures, points to the importance of counter cations and the solvation of the "empty" hosts, free guests, and host-guest complexes, in defining the affinity.

Automated adaptive inference of phenomenological dynamical models.

PubMed

Daniels, Bryan C; Nemenman, Ilya

2015-08-21

Dynamics of complex systems is often driven by large and intricate networks of microscopic interactions, whose sheer size obfuscates understanding. With limited experimental data, many parameters of such dynamics are unknown, and thus detailed, mechanistic models risk overfitting and making faulty predictions. At the other extreme, simple ad hoc models often miss defining features of the underlying systems. Here we develop an approach that instead constructs phenomenological, coarse-grained models of network dynamics that automatically adapt their complexity to the available data. Such adaptive models produce accurate predictions even when microscopic details are unknown. The approach is computationally tractable, even for a relatively large number of dynamical variables. Using simulated data, it correctly infers the phase space structure for planetary motion, avoids overfitting in a biological signalling system and produces accurate predictions for yeast glycolysis with tens of data points and over half of the interacting species unobserved.

A survey of noninteractive zero knowledge proof system and its applications.

PubMed

Wu, Huixin; Wang, Feng

2014-01-01

Zero knowledge proof system which has received extensive attention since it was proposed is an important branch of cryptography and computational complexity theory. Thereinto, noninteractive zero knowledge proof system contains only one message sent by the prover to the verifier. It is widely used in the construction of various types of cryptographic protocols and cryptographic algorithms because of its good privacy, authentication, and lower interactive complexity. This paper reviews and analyzes the basic principles of noninteractive zero knowledge proof system, and summarizes the research progress achieved by noninteractive zero knowledge proof system on the following aspects: the definition and related models of noninteractive zero knowledge proof system, noninteractive zero knowledge proof system of NP problems, noninteractive statistical and perfect zero knowledge, the connection between noninteractive zero knowledge proof system, interactive zero knowledge proof system, and zap, and the specific applications of noninteractive zero knowledge proof system. This paper also points out the future research directions.

Arctic tipping points: governance in turbulent times.

PubMed

Young, Oran R

2012-02-01

Interacting forces of climate change and globalization are transforming the Arctic. Triggered by a non-linear shift in sea ice, this transformation has unleashed mounting interest in opportunities to exploit the region's natural resources as well as growing concern about environmental, economic, and political issues associated with such efforts. This article addresses the implications of this transformation for governance, identifies limitations of existing arrangements, and explores changes needed to meet new demands. It advocates the development of an Arctic regime complex featuring flexibility across issues and adaptability over time along with an enhanced role for the Arctic Council both in conducting policy-relevant assessments and in promoting synergy in interactions among the elements of the emerging Arctic regime complex. The emphasis throughout is on maximizing the fit between the socioecological features of the Arctic and the character of the governance arrangements needed to steer the Arctic toward a sustainable future.

Automated adaptive inference of phenomenological dynamical models

PubMed Central

Daniels, Bryan C.; Nemenman, Ilya

2015-01-01

Dynamics of complex systems is often driven by large and intricate networks of microscopic interactions, whose sheer size obfuscates understanding. With limited experimental data, many parameters of such dynamics are unknown, and thus detailed, mechanistic models risk overfitting and making faulty predictions. At the other extreme, simple ad hoc models often miss defining features of the underlying systems. Here we develop an approach that instead constructs phenomenological, coarse-grained models of network dynamics that automatically adapt their complexity to the available data. Such adaptive models produce accurate predictions even when microscopic details are unknown. The approach is computationally tractable, even for a relatively large number of dynamical variables. Using simulated data, it correctly infers the phase space structure for planetary motion, avoids overfitting in a biological signalling system and produces accurate predictions for yeast glycolysis with tens of data points and over half of the interacting species unobserved. PMID:26293508

Modeling Electronic-Nuclear Interactions for Excitation Energy Transfer Processes in Light-Harvesting Complexes.

PubMed

Lee, Mi Kyung; Coker, David F

2016-08-18

An accurate approach for computing intermolecular and intrachromophore contributions to spectral densities to describe the electronic-nuclear interactions relevant for modeling excitation energy transfer processes in light harvesting systems is presented. The approach is based on molecular dynamics (MD) calculations of classical correlation functions of long-range contributions to excitation energy fluctuations and a separate harmonic analysis and single-point gradient quantum calculations for electron-intrachromophore vibrational couplings. A simple model is also presented that enables detailed analysis of the shortcomings of standard MD-based excitation energy fluctuation correlation function approaches. The method introduced here avoids these problems, and its reliability is demonstrated in accurate predictions for bacteriochlorophyll molecules in the Fenna-Matthews-Olson pigment-protein complex, where excellent agreement with experimental spectral densities is found. This efficient approach can provide instantaneous spectral densities for treating the influence of fluctuations in environmental dissipation on fast electronic relaxation.

Electrostatic contributions drive the interaction between Staphylococcus aureus protein Efb-C and its complement target C3d.

PubMed

Haspel, Nurit; Ricklin, Daniel; Geisbrecht, Brian V; Kavraki, Lydia E; Lambris, John D

2008-11-01

The C3-inhibitory domain of Staphylococcus aureus extracellular fibrinogen-binding protein (Efb-C) defines a novel three-helix bundle motif that regulates complement activation. Previous crystallographic studies of Efb-C bound to its cognate subdomain of human C3 (C3d) identified Arg-131 and Asn-138 of Efb-C as key residues for its activity. In order to characterize more completely the physical and chemical driving forces behind this important interaction, we employed in this study a combination of structural, biophysical, and computational methods to analyze the interaction of C3d with Efb-C and the single-point mutants R131A and N138A. Our results show that while these mutations do not drastically affect the structure of the Efb-C/C3d recognition complex, they have significant adverse effects on both the thermodynamic and kinetic profiles of the resulting complexes. We also characterized other key interactions along the Efb-C/C3d binding interface and found an intricate network of salt bridges and hydrogen bonds that anchor Efb-C to C3d, resulting in its potent complement inhibitory properties.

Theoretical investigation of gas-phase molecular complex formation between 2-hydroxy thiophenol and a water molecule.

PubMed

Kumar Deb, Debojit; Sarkar, Biplab

2017-01-18

The torsional potential of OH and SH rotations in 2-hydroxy thiophenol is systematically studied using the MP2 ab initio method. The outcome of state-of-the-art calculations is used in the investigation of the structures and conformational preferences of 2-hydroxy thiophenol and aims at further interaction studies with a gas phase water molecule. SCS-MP2 and CCSD(T) complete basis set (CBS) limit interaction energies for these complexes are presented. The SCS-MP2/CBS limit is achieved using various two-point extrapolation methods with aug-cc-pVDZ and aug-cc-pVTZ basis sets. The CCSD(T) correction term is determined as the difference between CCSD(T) and SCS-MP2 interaction energies calculated using a smaller basis set. The effect of counterpoise correction on the extrapolation to the CBS limit is discussed. The performance of DFT based wB97XD, M06-2X and B3LYP-D3 functionals is tested against the benchmark energy from ab initio calculations. Hydrogen bond interactions are characterized by carrying out QTAIM, NCIPLOT, NBO and SAPT analyses.

Epistatic interaction of genetic depression risk variants in the human subgenual cingulate cortex during memory encoding

PubMed Central

Schott, B H; Assmann, A; Schmierer, P; Soch, J; Erk, S; Garbusow, M; Mohnke, S; Pöhland, L; Romanczuk-Seiferth, N; Barman, A; Wüstenberg, T; Haddad, L; Grimm, O; Witt, S; Richter, S; Klein, M; Schütze, H; Mühleisen, T W; Cichon, S; Rietschel, M; Noethen, M M; Tost, H; Gundelfinger, E D; Düzel, E; Heinz, A; Meyer-Lindenberg, A; Seidenbecher, C I; Walter, H

2014-01-01

Recent genome-wide association studies have pointed to single-nucleotide polymorphisms (SNPs) in genes encoding the neuronal calcium channel CaV1.2 (CACNA1C; rs1006737) and the presynaptic active zone protein Piccolo (PCLO; rs2522833) as risk factors for affective disorders, particularly major depression. Previous neuroimaging studies of depression-related endophenotypes have highlighted the role of the subgenual cingulate cortex (CG25) in negative mood and depressive psychopathology. Here, we aimed to assess how recently associated PCLO and CACNA1C depression risk alleles jointly affect memory-related CG25 activity as an intermediate phenotype in clinically healthy humans. To investigate the combined effects of rs1006737 and rs2522833 on the CG25 response, we conducted three functional magnetic resonance imaging studies of episodic memory formation in three independent cohorts (N=79, 300, 113). An epistatic interaction of PCLO and CACNA1C risk alleles in CG25 during memory encoding was observed in all groups, with carriers of no risk allele and of both risk alleles showing higher CG25 activation during encoding when compared with carriers of only one risk allele. Moreover, PCLO risk allele carriers showed lower memory performance and reduced encoding-related hippocampal activation. In summary, our results point to region-specific epistatic effects of PCLO and CACNA1C risk variants in CG25, potentially related to episodic memory. Our data further suggest that genetic risk factors on the SNP level do not necessarily have additive effects but may show complex interactions. Such epistatic interactions might contribute to the ‘missing heritability' of complex phenotypes. PMID:24643163

Sensori-Motor Learning with Movement Sonification: Perspectives from Recent Interdisciplinary Studies.

PubMed

Bevilacqua, Frédéric; Boyer, Eric O; Françoise, Jules; Houix, Olivier; Susini, Patrick; Roby-Brami, Agnès; Hanneton, Sylvain

2016-01-01

This article reports on an interdisciplinary research project on movement sonification for sensori-motor learning. First, we describe different research fields which have contributed to movement sonification, from music technology including gesture-controlled sound synthesis, sonic interaction design, to research on sensori-motor learning with auditory-feedback. In particular, we propose to distinguish between sound-oriented tasks and movement-oriented tasks in experiments involving interactive sound feedback. We describe several research questions and recently published results on movement control, learning and perception. In particular, we studied the effect of the auditory feedback on movements considering several cases: from experiments on pointing and visuo-motor tracking to more complex tasks where interactive sound feedback can guide movements, or cases of sensory substitution where the auditory feedback can inform on object shapes. We also developed specific methodologies and technologies for designing the sonic feedback and movement sonification. We conclude with a discussion on key future research challenges in sensori-motor learning with movement sonification. We also point out toward promising applications such as rehabilitation, sport training or product design.

Density Functional Calculations of Native Defects in CH 3 NH 3 PbI 3 : Effects of Spin–Orbit Coupling and Self-Interaction Error

DOE PAGES

Du, Mao-Hua

2015-04-02

We know that native point defects play an important role in carrier transport properties of CH3NH3PbI3. However, the nature of many important defects remains controversial due partly to the conflicting results reported by recent density functional theory (DFT) calculations. In this Letter, we show that self-interaction error and the neglect of spin–orbit coupling (SOC) in many previous DFT calculations resulted in incorrect positions of valence and conduction band edges, although their difference, which is the band gap, is in good agreement with the experimental value. Moreover, this problem has led to incorrect predictions of defect-level positions. Hybrid density functional calculations,more » which partially correct the self-interaction error and include the SOC, show that, among native point defects (including vacancies, interstitials, and antisites), only the iodine vacancy and its complexes induce deep electron and hole trapping levels inside of the band gap, acting as nonradiative recombination centers.« less

Spectroscopic characterisation of interaction of ferulic acid with aldehyde dehydrogenase (ALDH).

PubMed

Kolawole, Ayodele O; Agaba, Ruth J; Oluwole, Matthew O

2017-05-01

Interaction of a pharmacological important phenolic, ferulic acid, with Aldehyde dehydrogenase (ALDH) at the simulative pH condition, was studied using spectroscopic approach. Ferulic acid caused a decrease in the fluorescence intensity formed from ALDH-ferulic acid complex resulting in mixed inhibition of ALDH activity (IC 50 =30.65μM). The intrinsic quenching was dynamic and induced altered conformation of ALDH and made the protein less compact but might not unfold it. ALDH has two binding sites for ferulic acid at saturating concentrations having association constant of 1.35×10 3 Lmol -1 and a dissociation constant of 9.7×10 7 Lmol -1 at 25°C indicating ALDH-ferulic acid complex formation is more favourable than its dissociation. The interaction was not spontaneous and endothermic and suggests the involvement of hydrophobic interactions with a FRET binding distance of 4.49nm. Change in pH near and far from isoelectric points of ferulic acid did not affect the bonding interaction. Using trehalose as viscosogen, the result from Stoke-Einstein hypothesis showed that ferulic acid-ALDH binding and dissociation equilibrium was diffusion controlled. These results clearly suggest the unique binding properties and lipophilicity influence of ferulic acid. Copyright © 2017 Elsevier B.V. All rights reserved.

A microscopic evaluation of collagen-bilirubin interactions: in vitro surface phenomenon.

PubMed

Usharani, N; Jayakumar, G C; Rao, J R; Chandrasekaran, B; Nair, B U

2014-02-01

This study is carried out to understand the morphology variations of collagen I matrices influenced by bilirubin. The characteristics of bilirubin interaction with collagen ascertained using various techniques like XRD, CLSM, fluorescence, SEM and AFM. These techniques are used to understand the distribution, expression and colocalization patterns of collagen-bilirubin complexes. The present investigation mimic the in vivo mechanisms created during the disorder condition like jaundice. Fluorescence technique elucidates the crucial role played by bilirubin deposition and interaction during collagen organization. Influence of bilirubin during collagen fibrillogenesis and banding patterns are clearly visualize using SEM. As a result, collagen-bilirubin complex provides different reconstructed patterns because of the influence of bilirubin concentration. Selectivity, specificity and spatial organization of collagen-bilirubin are determined through AFM imaging. Consequently, it is observed that the morphology and quantity of the bilirubin binding to collagen varied by the concentrations and the adsorption rate in protein solutions. Microscopic studies of collagen-bilirubin interaction confirms that bilirubin influence the fibrillogenesis and alter the rate of collagen organization depending on the bilirubin concentration. This knowledge helps to develop a novel drug to inhibit the interface point of interaction between collagen and bilirubin. © 2013 The Authors Journal of Microscopy © 2013 Royal Microscopical Society.

The cystic fibrosis microbiome in an ecological perspective and its impact in antibiotic therapy.

PubMed

Magalhães, Andreia P; Azevedo, Nuno F; Pereira, Maria O; Lopes, Susana P

2016-02-01

The recent focus on the cystic fibrosis (CF) complex microbiome has led to the recognition that the microbes can interact between them and with the host immune system, affecting the disease progression and treatment routes. Although the main focus remains on the interactions between traditional pathogens, growing evidence supports the contribution and the role of emergent species. Understanding the mechanisms and the biological effects involved in polymicrobial interactions may be the key to improve effective therapies and also to define new strategies for disease control. This review focuses on the interactions between microbe-microbe and host-microbe, from an ecological point of view, discussing their impact on CF disease progression. There are increasing indications that these interactions impact the success of antimicrobial therapy. Consequently, a new approach where therapy is personalized to patients by taking into account their individual CF microbiome is suggested.

Interaction of cationic surfactants with DNA: a single-molecule study

PubMed Central

Husale, Sudhir; Grange, Wilfried; Karle, Marc; Bürgi, Stephan; Hegner, Martin

2008-01-01

The interaction of cationic surfactants with single dsDNA molecules has been studied using force-measuring optical tweezers. For hydrophobic chains of length 12 and greater, pulling experiments show characteristic features (e.g. hysteresis between the pulling and relaxation curves, force-plateau along the force curves), typical of a condensed phase (compaction of a long DNA into a micron-sized particle). Depending on the length of the hydrophobic chain of the surfactant, we observe different mechanical behaviours of the complex (DNA-surfactants), which provide evidence for different binding modes. Taken together, our measurements suggest that short-chain surfactants, which do not induce any condensation, could lie down on the DNA surface and directly interact with the DNA grooves through hydrophobic–hydrophobic interactions. In contrast, long-chain surfactants could have their aliphatic tails pointing away from the DNA surface, which could promote inter-molecular interactions between hydrophobic chains and subsequently favour DNA condensation. PMID:18203749

Low-Energy Collisions of Protonated Enantiopure Amino Acids with Chiral Target Gases

NASA Astrophysics Data System (ADS)

Kulyk, K.; Rebrov, O.; Ryding, M.; Thomas, R. D.; Uggerud, E.; Larsson, M.

2017-12-01

Here we report on the gas-phase interactions between protonated enantiopure amino acids ( l- and d-enantiomers of Met, Phe, and Trp) and chiral target gases [( R)- and ( S)-2-butanol, and ( S)-1-phenylethanol] in 0.1-10.0 eV low-energy collisions. Two major processes are seen to occur over this collision energy regime, collision-induced dissociation and ion-molecule complex formation. Both processes were found to be independent of the stereo-chemical composition of the interacting ions and targets. These data shed light on the currently debated mechanisms of gas-phase chiral selectivity by demonstrating the inapplicability of the three-point model to these interactions, at least under single collision conditions. [Figure not available: see fulltext.

Bioluminescence methodology for the detection of protein-protein interactions within the voltage-gated sodium channel macromolecular complex.

PubMed

Shavkunov, Alexander; Panova, Neli; Prasai, Anesh; Veselenak, Ron; Bourne, Nigel; Stoilova-McPhie, Svetla; Laezza, Fernanda

2012-04-01

Protein-protein interactions are critical molecular determinants of ion channel function and emerging targets for pharmacological interventions. Yet, current methodologies for the rapid detection of ion channel macromolecular complexes are still lacking. In this study we have adapted a split-luciferase complementation assay (LCA) for detecting the assembly of the voltage-gated Na+ (Nav) channel C-tail and the intracellular fibroblast growth factor 14 (FGF14), a functionally relevant component of the Nav channelosome that controls gating and targeting of Nav channels through direct interaction with the channel C-tail. In the LCA, two complementary N-terminus and C-terminus fragments of the firefly luciferase were fused, respectively, to a chimera of the CD4 transmembrane segment and the C-tail of Nav1.6 channel (CD4-Nav1.6-NLuc) or FGF14 (CLuc-FGF14). Co-expression of CLuc-FGF14 and CD4-Nav1.6-NLuc in live cells led to a robust assembly of the FGF14:Nav1.6 C-tail complex, which was attenuated by introducing single-point mutations at the predicted FGF14:Nav channel interface. To evaluate the dynamic regulation of the FGF14:Nav1.6 C-tail complex by signaling pathways, we investigated the effect of kinase inhibitors on the complex formation. Through a platform of counter screenings, we show that the p38/MAPK inhibitor, PD169316, and the IκB kinase inhibitor, BAY 11-7082, reduce the FGF14:Nav1.6 C-tail complementation, highlighting a potential role of the p38MAPK and the IκB/NFκB pathways in controlling neuronal excitability through protein-protein interactions. We envision the methodology presented here as a new valuable tool to allow functional evaluations of protein-channel complexes toward probe development and drug discovery targeting ion channels implicated in human disorders.

Stirring Up an Elastic Fluid: Critical Viscosity of Xenon-2 (CVX-2)

NASA Astrophysics Data System (ADS)

Berg, Robert F.; Moldover, Michael R.; Zimmerli, Gregory A.

2002-12-01

Whipped cream stays in place even when turned upside down. Yet it readily flows through the nozzle of a spray can to reach the dessert plate. This demonstrates the phenomenon of shear thinning that is important to many industrial and physical processes. Paints, film emulsions, and other complex solutions that are highly viscous under normal conditions but become thin and flow easily under shear forces. A simple fluid, such as water, does not exhibit shear thinning under normal conditions. Very close to the liquid-vapor critical point, where the distinction between liquid and vapor disappears, the fluid becomes more complex and is predicted to display shear thinning. At the critical point, xenon atoms interact over long distances in a classical model of cooperative phenomena. Physicists rely on this system to learn how long-range order arises. The Critical Viscosity of Xenon Experiment (CVX-2) will measure the viscous behavior of xenon, a heavy inert gas used in flash lamps and ion rocket engines, at its critical point. Although it does not easily combine with other chemicals, its viscosity at the critical point can be used as a model for a range of fluids. Viscosity originates from the interactions of individual molecules. It is so complicated that, except for the simplest gas, it cannot be calculated accurately from theory. Tests with critical fluids can provide key data, but are limited on Earth because critical fluids are highly compressed by gravity. CVX-2 employs a tiny metal screen vibrating between two electrodes in a bath of critical xenon. The vibrations and how they dampen are used to measure viscosity. CVX flew on STS-85 (1997), where it revealed that, close to the critical point, the xenon is partly elastic: it can 'stretch' as well as flow. For STS-107, the hardware has been enhanced to determine if critical xenon is a shear-thinning fluid.

Stirring Up an Elastic Fluid: Critical Viscosity of Xenon-2 (CVX-2)

NASA Technical Reports Server (NTRS)

Berg, Robert F.; Moldover, Michael R.; Zimmerli, Gregory A.; Motil, Susan M. (Technical Monitor)

2002-01-01

Whipped cream stays in place even when turned upside down. Yet it readily flows through the nozzle of a spray can to reach the dessert plate. This demonstrates the phenomenon of shear thinning that is important to many industrial and physical processes. Paints, film emulsions, and other complex solutions that are highly viscous under normal conditions but become thin and flow easily under shear forces. A simple fluid, such as water, does not exhibit shear thinning under normal conditions. Very close to the liquid-vapor critical point, where the distinction between liquid and vapor disappears, the fluid becomes more complex and is predicted to display shear thinning. At the critical point, xenon atoms interact over long distances in a classical model of cooperative phenomena. Physicists rely on this system to learn how long-range order arises. The Critical Viscosity of Xenon Experiment (CVX-2) will measure the viscous behavior of xenon, a heavy inert gas used in flash lamps and ion rocket engines, at its critical point. Although it does not easily combine with other chemicals, its viscosity at the critical point can be used as a model for a range of fluids. Viscosity originates from the interactions of individual molecules. It is so complicated that, except for the simplest gas, it cannot be calculated accurately from theory. Tests with critical fluids can provide key data, but are limited on Earth because critical fluids are highly compressed by gravity. CVX-2 employs a tiny metal screen vibrating between two electrodes in a bath of critical xenon. The vibrations and how they dampen are used to measure viscosity. CVX flew on STS-85 (1997), where it revealed that, close to the critical point, the xenon is partly elastic: it can 'stretch' as well as flow. For STS-107, the hardware has been enhanced to determine if critical xenon is a shear-thinning fluid.

Reply to comment by Jonathan J. Rhodes on "Modeling of the interactions between forest vegetation, disturbances, and sediment yields"

Treesearch

Charles H. Luce; David G. Tarboton; Erkan Istanbulluoglu; Robert T. Pack

2005-01-01

Rhodes [2005] brings up some excellent points in his comments on the work of Istanbulluoglu et al. [2004]. We appreciate the opportunity to respond because it is likely that other readers will also wonder how they can apply the relatively simple analysis to important policy questions. Models necessarily reduce the complexity of the problem to make it tractable and...

Investigating the Interaction between the Neonatal Fc Receptor and Monoclonal Antibody Variants by Hydrogen/Deuterium Exchange Mass Spectrometry*

PubMed Central

Jensen, Pernille Foged; Larraillet, Vincent; Schlothauer, Tilman; Kettenberger, Hubert; Hilger, Maximiliane; Rand, Kasper D.

2015-01-01

The recycling of immunoglobulins by the neonatal Fc receptor (FcRn) is of crucial importance in the maintenance of antibody levels in plasma and is responsible for the long half-lives of endogenous and recombinant monoclonal antibodies. From a therapeutic point of view there is great interest in understanding and modulating the IgG–FcRn interaction to optimize antibody pharmacokinetics and ultimately improve efficacy and safety. Here we studied the interaction between a full-length human IgG1 and human FcRn via hydrogen/deuterium exchange mass spectrometry and targeted electron transfer dissociation to map sites perturbed by binding on both partners of the IgG–FcRn complex. Several regions in the antibody Fc region and the FcRn were protected from exchange upon complex formation, in good agreement with previous crystallographic studies of FcRn in complex with the Fc fragment. Interestingly, we found that several regions in the IgG Fab region also showed reduced deuterium uptake. Our findings indicate the presence of hitherto unknown FcRn interaction sites in the Fab region or a possible conformational link between the IgG Fc and Fab regions upon FcRn binding. Further, we investigated the role of IgG glycosylation in the conformational response of the IgG–FcRn interaction. Removal of antibody glycans increased the flexibility of the FcRn binding site in the Fc region. Consequently, FcRn binding did not induce a similar conformational stabilization of deglycosylated IgG as observed for the wild-type glycosylated IgG. Our results provide new molecular insight into the IgG–FcRn interaction and illustrate the capability of hydrogen/deuterium exchange mass spectrometry to advance structural proteomics by providing detailed information on the conformation and dynamics of large protein complexes in solution. PMID:25378534

CH-π Interaction Driven Macroscopic Property Transition on Smart Polymer Surface

NASA Astrophysics Data System (ADS)

Li, Minmin; Qing, Guangyan; Xiong, Yuting; Lai, Yuekun; Sun, Taolei

2015-10-01

Life systems have evolved to utilize weak noncovalent interactions, particularly CH-π interaction, to achieve various biofunctions, for example cellular communication, immune response, and protein folding. However, for artificial materials, it remains a great challenge to recognize such weak interaction, further transform it into tunable macroscopic properties and realize special functions. Here we integrate monosaccharide-based CH-π receptor capable of recognizing aromatic peptides into a smart polymer with three-component “Recognition-Mediating-Function” design, and report the CH-π interaction driven surface property switching on smart polymer film, including wettability, adhesion, viscoelasticity and stiffness. Detailed studies indicate that, the CH-π interaction induces the complexation between saccharide unit and aromatic peptide, which breaks the initial amphiphilic balance of the polymer network, resulting in contraction-swelling conformational transition for polymer chains and subsequent dramatic switching in surface properties. This work not only presents a new approach to control the surface property of materials, but also points to a broader research prospect on CH-π interaction at a macroscopic level.

CH-π Interaction Driven Macroscopic Property Transition on Smart Polymer Surface.

PubMed

Li, Minmin; Qing, Guangyan; Xiong, Yuting; Lai, Yuekun; Sun, Taolei

2015-10-29

Life systems have evolved to utilize weak noncovalent interactions, particularly CH-π interaction, to achieve various biofunctions, for example cellular communication, immune response, and protein folding. However, for artificial materials, it remains a great challenge to recognize such weak interaction, further transform it into tunable macroscopic properties and realize special functions. Here we integrate monosaccharide-based CH-π receptor capable of recognizing aromatic peptides into a smart polymer with three-component "Recognition-Mediating-Function" design, and report the CH-π interaction driven surface property switching on smart polymer film, including wettability, adhesion, viscoelasticity and stiffness. Detailed studies indicate that, the CH-π interaction induces the complexation between saccharide unit and aromatic peptide, which breaks the initial amphiphilic balance of the polymer network, resulting in contraction-swelling conformational transition for polymer chains and subsequent dramatic switching in surface properties. This work not only presents a new approach to control the surface property of materials, but also points to a broader research prospect on CH-π interaction at a macroscopic level.

Inhibition of the Membrane Attack Complex by Dengue Virus NS1 through Interaction with Vitronectin and Terminal Complement Proteins

PubMed Central

Conde, Jonas Nascimento; da Silva, Emiliana Mandarano; Allonso, Diego; Coelho, Diego Rodrigues; Andrade, Iamara da Silva; de Medeiros, Luciano Neves; Menezes, Joice Lima; Barbosa, Angela Silva

2016-01-01

ABSTRACT Dengue virus (DENV) infects millions of people worldwide and is a major public health problem. DENV nonstructural protein 1 (NS1) is a conserved glycoprotein that associates with membranes and is also secreted into the plasma in DENV-infected patients. The present study describes a novel mechanism by which NS1 inhibits the terminal complement pathway. We first identified the terminal complement regulator vitronectin (VN) as a novel DENV2 NS1 binding partner by using a yeast two-hybrid system. This interaction was further assessed by enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) assay. The NS1-VN complex was also detected in plasmas from DENV-infected patients, suggesting that this interaction occurs during DENV infection. We also demonstrated that the DENV2 NS1 protein, either by itself or by interacting with VN, hinders the formation of the membrane attack complex (MAC) and C9 polymerization. Finally, we showed that DENV2, West Nile virus (WNV), and Zika virus (ZIKV) NS1 proteins produced in mammalian cells inhibited C9 polymerization. Taken together, our results points to a role for NS1 as a terminal pathway inhibitor of the complement system. IMPORTANCE Dengue is the most important arthropod-borne viral disease nowadays and is caused by dengue virus (DENV). The flavivirus NS1 glycoprotein has been characterized functionally as a complement evasion protein that can attenuate the activation of the classical, lectin, and alternative pathways. The present study describes a novel mechanism by which DENV NS1 inhibits the terminal complement pathway. We identified the terminal complement regulator vitronectin (VN) as a novel DENV NS1 binding partner, and the NS1-VN complex was detected in plasmas from DENV-infected patients, suggesting that this interaction occurs during DENV infection. We also demonstrated that the NS1-VN complex inhibited membrane attack complex (MAC) formation, thus interfering with the complement terminal pathway. Interestingly, NS1 itself also inhibited MAC activity, suggesting a direct role of this protein in the inhibition process. Our findings imply a role for NS1 as a terminal pathway inhibitor of the complement system. PMID:27512066

Numerical propulsion system simulation

NASA Technical Reports Server (NTRS)

Lytle, John K.; Remaklus, David A.; Nichols, Lester D.

1990-01-01

The cost of implementing new technology in aerospace propulsion systems is becoming prohibitively expensive. One of the major contributors to the high cost is the need to perform many large scale system tests. Extensive testing is used to capture the complex interactions among the multiple disciplines and the multiple components inherent in complex systems. The objective of the Numerical Propulsion System Simulation (NPSS) is to provide insight into these complex interactions through computational simulations. This will allow for comprehensive evaluation of new concepts early in the design phase before a commitment to hardware is made. It will also allow for rapid assessment of field-related problems, particularly in cases where operational problems were encountered during conditions that would be difficult to simulate experimentally. The tremendous progress taking place in computational engineering and the rapid increase in computing power expected through parallel processing make this concept feasible within the near future. However it is critical that the framework for such simulations be put in place now to serve as a focal point for the continued developments in computational engineering and computing hardware and software. The NPSS concept which is described will provide that framework.

Structural basis for midbody targeting of spastin by the ESCRT-III protein CHMP1B

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

Yang, Dong; Rimanchi, Neggy; Renvoise, Benoit

2009-01-15

The endosomal sorting complex required for transport (ESCRT) machinery, including ESCRT-III, localizes to the midbody and participates in the membrane-abscission step of cytokinesis. The ESCRT-III protein charged multivesicular body protein 1B (CHMP1B) is required for recruitment of the MIT domain-containing protein spastin, a microtubule-severing enzyme, to the midbody. The 2.5-{angstrom} structure of the C-terminal tail of CHMP1B with the MIT domain of spastin reveals a specific, high-affinity complex involving a noncanonical binding site between the first and third helices of the MIT domain. The structural interface is twice as large as that of the MIT domain of the VPS4-CHMP complex,more » consistent with the high affinity of the interaction. A series of unique hydrogen-bonding interactions and close packing of small side chains discriminate against the other ten human ESCRT-III subunits. Point mutants in the CHMP1B binding site of spastin block recruitment of spastin to the midbody and impair cytokinesis.« less

Atmospheric processes over complex terrain

NASA Astrophysics Data System (ADS)

Banta, Robert M.; Berri, G.; Blumen, William; Carruthers, David J.; Dalu, G. A.; Durran, Dale R.; Egger, Joseph; Garratt, J. R.; Hanna, Steven R.; Hunt, J. C. R.

1990-06-01

A workshop on atmospheric processes over complex terrain, sponsored by the American Meteorological Society, was convened in Park City, Utah from 24 vto 28 October 1988. The overall objective of the workshop was one of interaction and synthesis--interaction among atmospheric scientists carrying out research on a variety of orographic flow problems, and a synthesis of their results and points of view into an assessment of the current status of topical research problems. The final day of the workshop was devoted to an open discussion on the research directions that could be anticipated in the next decade because of new and planned instrumentation and observational networks, the recent emphasis on development of mesoscale numerical models, and continual theoretical investigations of thermally forced flows, orographic waves, and stratified turbulence. This monograph represents an outgrowth of the Park City Workshop. The authors have contributed chapters based on their lecture material. Workshop discussions indicated interest in both the remote sensing and predictability of orographic flows. These chapters were solicited following the workshop in order to provide a more balanced view of current progress and future directions in research on atmospheric processes over complex terrain.

Interaction of monovalent cations with acetonitrile

NASA Astrophysics Data System (ADS)

Černušák, Ivan; Aranyosiová, Monika; Vollárová, Ol'ga; Velič, Dušan; Kirdajová, Ol'ga; Benko, Ján

Solvation of monovalent cations (Me+) of alkali metals=Na+, K+, Rb+, and Cs+, coinage metals=Cu+, Ag+, Au+, and p-block elements Ga+, In+, and Tl+ with acetonitrile was studied by means of ab initio calculations and time-of-flight secondary ion mass spectrometry (TOF-SIMS). The intermolecular interactions in the complexes Me+···CH3CN were investigated using the coupled clusters theory including single, double, and noniterative triple substitutions (CCSD(T)) in conjunction with the Pol and Pol-dk basis sets. The binding energies of these donor-acceptor complexes were estimated; taking into account the basis set superposition error, zero-point vibrations, correlation contribution, and scalar relativistic corrections. The theoretical ΔG0298 K values based on CCSD(T)/Pol and/or CCSD(T)/Pol-dk binding energies correlated well with experimental transfer Gibbs energies (from water to acetonitrile) for the series of cations. In the case of Au monocation, relativistic correction turned out to be extremely important. Composition of the complex of Ag+ and Na+ with acetonitrile was determined by using SIMS supporting both theoretical and experimental transfer Gibbs energies.

The complex and specific pMHC interactions with diverse HIV-1 TCR clonotypes reveal a structural basis for alterations in CTL function

NASA Astrophysics Data System (ADS)

Xia, Zhen; Chen, Huabiao; Kang, Seung-Gu; Huynh, Tien; Fang, Justin W.; Lamothe, Pedro A.; Walker, Bruce D.; Zhou, Ruhong

2014-02-01

Immune control of viral infections is modulated by diverse T cell receptor (TCR) clonotypes engaging peptide-MHC class I complexes on infected cells, but the relationship between TCR structure and antiviral function is unclear. Here we apply in silico molecular modeling with in vivo mutagenesis studies to investigate TCR-pMHC interactions from multiple CTL clonotypes specific for a well-defined HIV-1 epitope. Our molecular dynamics simulations of viral peptide-HLA-TCR complexes, based on two independent co-crystal structure templates, reveal that effective and ineffective clonotypes bind to the terminal portions of the peptide-MHC through similar salt bridges, but their hydrophobic side-chain packings can be very different, which accounts for the major part of the differences among these clonotypes. Non-specific hydrogen bonding to viral peptide also accommodates greater epitope variants. Furthermore, free energy perturbation calculations for point mutations on the viral peptide KK10 show excellent agreement with in vivo mutagenesis assays, with new predictions confirmed by additional experiments. These findings indicate a direct structural basis for heterogeneous CTL antiviral function.

Integrating the invisible fabric of nature into fisheries management

PubMed Central

Travis, Joseph; Coleman, Felicia C.; Auster, Peter J.; Cury, Philippe M.; Estes, James A.; Orensanz, Jose; Peterson, Charles H.; Power, Mary E.; Steneck, Robert S.; Wootton, J. Timothy

2014-01-01

Overfishing and environmental change have triggered many severe and unexpected consequences. As existing communities have collapsed, new ones have become established, fundamentally transforming ecosystems to those that are often less productive for fisheries, more prone to cycles of booms and busts, and thus less manageable. We contend that the failure of fisheries science and management to anticipate these transformations results from a lack of appreciation for the nature, strength, complexity, and outcome of species interactions. Ecologists have come to understand that networks of interacting species exhibit nonlinear dynamics and feedback loops that can produce sudden and unexpected shifts. We argue that fisheries science and management must follow this lead by developing a sharper focus on species interactions and how disrupting these interactions can push ecosystems in which fisheries are embedded past their tipping points. PMID:24367087

Representation and display of vector field topology in fluid flow data sets

NASA Technical Reports Server (NTRS)

Helman, James; Hesselink, Lambertus

1989-01-01

The visualization of physical processes in general and of vector fields in particular is discussed. An approach to visualizing flow topology that is based on the physics and mathematics underlying the physical phenomenon is presented. It involves determining critical points in the flow where the velocity vector vanishes. The critical points, connected by principal lines or planes, determine the topology of the flow. The complexity of the data is reduced without sacrificing the quantitative nature of the data set. By reducing the original vector field to a set of critical points and their connections, a representation of the topology of a two-dimensional vector field that is much smaller than the original data set but retains with full precision the information pertinent to the flow topology is obtained. This representation can be displayed as a set of points and tangent curves or as a graph. Analysis (including algorithms), display, interaction, and implementation aspects are discussed.

Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration

PubMed Central

van Dijk, Gertjan; van Heijningen, Steffen; Reijne, Aaffien C.; Nyakas, Csaba; van der Zee, Eddy A.; Eisel, Ulrich L. M.

2015-01-01

Alzheimer's disease (AD) is a complex, multifactorial disease with a number of leading mechanisms, including neuroinflammation, processing of amyloid precursor protein (APP) to amyloid β peptide, tau protein hyperphosphorylation, relocalization, and deposition. These mechanisms are propagated by obesity, the metabolic syndrome and type-2 diabetes mellitus. Stress, sedentariness, dietary overconsumption of saturated fat and refined sugars, and circadian derangements/disturbed sleep contribute to obesity and related metabolic diseases, but also accelerate age-related damage and senescence that all feed the risk of developing AD too. The complex and interacting mechanisms are not yet completely understood and will require further analysis. Instead of investigating AD as a mono- or oligocausal disease we should address the disease by understanding the multiple underlying mechanisms and how these interact. Future research therefore might concentrate on integrating these by “systems biology” approaches, but also to regard them from an evolutionary medicine point of view. The current review addresses several of these interacting mechanisms in animal models and compares them with clinical data giving an overview about our current knowledge and puts them into an integrated framework. PMID:26041981

The basic amino acids in the coiled-coil domain of CIN85 regulate its interaction with c-Cbl and phosphatidic acid during epidermal growth factor receptor (EGFR) endocytosis

PubMed Central

2014-01-01

Background During EGFR internalization CIN85 bridges EGFR-Cbl complex, endocytic machinery and fusible membrane through the interactions of CIN85 with c-Cbl, endophilins and phosphatidic acid. These protein-protein and protein-lipid interactions are mediated or regulated by the positively charged C-terminal coiled-coil domain of CIN85. However, the details of CIN85-lipid interaction remain unknown. The present study suggested a possible electric interaction between the negative charge of phosphatidic acid and the positive charge of basic amino acids in coiled-coil domain. Results Mutations of the basic amino acids in the coiled-coil domain, especially K645, K646, R648 and R650, into neutral amino acid alanine completely blocked the interaction of CIN85 with c-Cbl or phosphatidic acid. However, they did not affect CIN85-endophilin interaction. In addition, CIN85 was found to associate with the internalized EGFR endosomes. It interacted with several ESCRT (Endosomal Sorting Complex Required for Transport) component proteins for ESCRT assembly on endosomal membrane. Mutations in the coiled-coil domain (deletion of the coiled-coil domain or point mutations of the basic amino acids) dissociated CIN85 from endosomes. These mutants bound the ESCRT components in cytoplasm to prevent them from assembly on endosomal membrane and inhibited EGFR sorting for degradation. Conclusions As an adaptor protein, CIN85 interacts with variety of partners through several domains. The positive charges of basic amino acids in the coiled-coil domain are not only involved in the interaction with phosphatidic acid, but also regulate the interaction of CIN85 with c-Cbl. CIN85 also interacts with ESCRT components for protein sorting in endosomes. These CIN85-protein and CIN85-lipid interactions enable CIN85 to link EGFR-Cbl endocytic complex with fusible membrane during EGFR endocytosis and subsequently to facilitate ESCRT formation on endosomal membrane for EGFR sorting and degradation. PMID:25005938

Complexity in pH-Dependent Ribozyme Kinetics: Dark pKa Shifts and Wavy Rate-pH Profiles.

PubMed

Frankel, Erica A; Bevilacqua, Philip C

2018-02-06

Charged bases occur in RNA enzymes, or ribozymes, where they play key roles in catalysis. Cationic bases donate protons and perform electrostatic catalysis, while anionic bases accept protons. We previously published simulations of rate-pH profiles for ribozymes in terms of species plots for the general acid and general base that have been useful for understanding how ribozymes respond to pH. In that study, we did not consider interaction between the general acid and general base or interaction with other species on the RNA. Since that report, diverse small ribozyme classes have been discovered, many of which have charged nucleobases or metal ions in the active site that can either directly interact and participate in catalysis or indirectly interact as "influencers". Herein, we simulate experimental rate-pH profiles in terms of species plots in which reverse protonated charged nucleobases interact. These analyses uncover two surprising features of pH-dependent enzyme kinetics. (1) Cooperativity between the general acid and general base enhances population of the functional forms of a ribozyme and manifests itself as hidden or "dark" pK a shifts, real pK a shifts that accelerate the reaction but are not readily observed by standard experimental approaches, and (2) influencers favorably shift the pK a s of proton-transferring nucleobases and manifest themselves as "wavy" rate-pH profiles. We identify parallels with the protein enzyme literature, including reverse protonation and wavelike behavior, while pointing out that RNA is more prone to reverse protonation. The complexities uncovered, which arise from simple pairwise interactions, should aid deconvolution of complex rate-pH profiles for RNA and protein enzymes and suggest veiled catalytic devices for promoting catalysis that can be tested by experiment and calculation.

Hepatitis C Virus Proteins Interact with the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery via Ubiquitination To Facilitate Viral Envelopment

PubMed Central

Barouch-Bentov, Rina; Neveu, Gregory; Xiao, Fei; Beer, Melanie; Bekerman, Elena; Schor, Stanford; Campbell, Joseph; Boonyaratanakornkit, Jim; Lindenbach, Brett; Lu, Albert; Jacob, Yves

2016-01-01

ABSTRACT Enveloped viruses commonly utilize late-domain motifs, sometimes cooperatively with ubiquitin, to hijack the endosomal sorting complex required for transport (ESCRT) machinery for budding at the plasma membrane. However, the mechanisms underlying budding of viruses lacking defined late-domain motifs and budding into intracellular compartments are poorly characterized. Here, we map a network of hepatitis C virus (HCV) protein interactions with the ESCRT machinery using a mammalian-cell-based protein interaction screen and reveal nine novel interactions. We identify HRS (hepatocyte growth factor-regulated tyrosine kinase substrate), an ESCRT-0 complex component, as an important entry point for HCV into the ESCRT pathway and validate its interactions with the HCV nonstructural (NS) proteins NS2 and NS5A in HCV-infected cells. Infectivity assays indicate that HRS is an important factor for efficient HCV assembly. Specifically, by integrating capsid oligomerization assays, biophysical analysis of intracellular viral particles by continuous gradient centrifugations, proteolytic digestion protection, and RNase digestion protection assays, we show that HCV co-opts HRS to mediate a late assembly step, namely, envelopment. In the absence of defined late-domain motifs, K63-linked polyubiquitinated lysine residues in the HCV NS2 protein bind the HRS ubiquitin-interacting motif to facilitate assembly. Finally, ESCRT-III and VPS/VTA1 components are also recruited by HCV proteins to mediate assembly. These data uncover involvement of ESCRT proteins in intracellular budding of a virus lacking defined late-domain motifs and a novel mechanism by which HCV gains entry into the ESCRT network, with potential implications for other viruses. PMID:27803188

Genotype-environment interaction and sociology: contributions and complexities.

PubMed

Seabrook, Jamie A; Avison, William R

2010-05-01

Genotype-environment interaction (G x E) refers to situations in which genetic effects connected to a phenotype are dependent upon variability in the environment, or when genes modify an organism's sensitivity to particular environmental features. Using a typology suggested in the G x E literature, we provide an overview of recent papers that show how social context can trigger a genetic vulnerability, compensate for a genetic vulnerability, control behaviors for which a genetic vulnerability exists, and improve adaptation via proximal causes. We argue that to improve their understanding of social structure, sociologists can take advantage of research in behavior genetics by assessing the impact of within-group variance of various health outcomes and complex human behaviors that are explainable by genotype, environment and their interaction. Insights from life course sociology can aid in ensuring that the dynamic nature of the environment in G x E has been accounted for. Identification of an appropriate entry point for sociologists interested in G x E research could begin with the choice of an environmental feature of interest, a genetic factor of interest, and/or behavior of interest. Optimizing measurement in order to capture the complexity of G x E is critical. Examining the interaction between poorly measured environmental factors and well measured genetic variables will overestimate the effects of genetic variables while underestimating the effect of environmental influences, thereby distorting the interaction between genotype and environment. Although the expense of collecting environmental data is very high, reliable and precise measurement of an environmental pathogen enhances a study's statistical power. Copyright 2010 Elsevier Ltd. All rights reserved.

Binding energies and spatial structures of small carrier complexes in monolayer transition-metal dichalcogenides via diffusion Monte Carlo

DOE PAGES

Mayers, Matthew Z.; Berkelbach, Timothy C.; Hybertsen, Mark S.; ...

2015-10-09

Ground-state diffusion Monte Carlo is used to investigate the binding energies and intercarrier radial probability distributions of excitons, trions, and biexcitons in a variety of two-dimensional transition-metal dichalcogenide materials. We compare these results to approximate variational calculations, as well as to analogous Monte Carlo calculations performed with simplified carrier interaction potentials. Our results highlight the successes and failures of approximate approaches as well as the physical features that determine the stability of small carrier complexes in monolayer transition-metal dichalcogenide materials. In conclusion, we discuss points of agreement and disagreement with recent experiments.

Modelling the morphodynamics and co-evolution of coast and estuarine environments

NASA Astrophysics Data System (ADS)

Morris, Chloe; Coulthard, Tom; Parsons, Daniel R.; Manson, Susan; Barkwith, Andrew

2017-04-01

The morphodynamics of coast and estuarine environments are known to be sensitive to environmental change and sea-level rise. However, whilst these systems have received considerable individual research attention, how they interact and co-evolve is relatively understudied. These systems are intrinsically linked and it is therefore advantageous to study them holistically in order to build a more comprehensive understanding of their behaviour and to inform sustainable management over the long term. Complex environments such as these are often studied using numerical modelling techniques. Inherent from the limited research in this area, existing models are currently not capable of simulating dynamic coast-estuarine interactions. A new model is being developed through coupling the one-line Coastline Evolution Model (CEM) with CAESAR-Lisflood (C-L), a hydrodynamic Landscape Evolution Model. It is intended that the eventual model be used to advance the understanding of these systems and how they may evolve over the mid to long term in response to climate change. In the UK, the Holderness Coast, Humber Estuary and Spurn Point system offers a diverse and complex case study for this research. Holderness is one of the fastest eroding coastlines in Europe and research suggests that the large volumes of material removed from its cliffs are responsible for the formation of the Spurn Point feature and for the Holocene infilling of the Humber Estuary. Marine, fluvial and coastal processes are continually reshaping this system and over the next century, it is predicted that climate change could lead to increased erosion along the coast and supply of material to the Humber Estuary and Spurn Point. How this manifests will be hugely influential to the future morphology of these systems and the existence of Spurn Point. Progress to date includes a new version of the CEM that has been prepared for integration into C-L and includes an improved graphical user interface and more complex geomorphological processes. Preliminary results from simulations of the Holderness Coast and Spurn Point support findings of other authors, who suggest that changes to the wave climate influences sediment transport patterns in the nearshore zone. The angle of wave approach to the Holderness shows particular significance compared to the height of waves, with an optimum volume of material transported at 42 degrees. Further applications and results of this new model will be presented and discussed.

Offdiagonal complexity: A computationally quick complexity measure for graphs and networks

NASA Astrophysics Data System (ADS)

Claussen, Jens Christian

2007-02-01

A vast variety of biological, social, and economical networks shows topologies drastically differing from random graphs; yet the quantitative characterization remains unsatisfactory from a conceptual point of view. Motivated from the discussion of small scale-free networks, a biased link distribution entropy is defined, which takes an extremum for a power-law distribution. This approach is extended to the node-node link cross-distribution, whose nondiagonal elements characterize the graph structure beyond link distribution, cluster coefficient and average path length. From here a simple (and computationally cheap) complexity measure can be defined. This offdiagonal complexity (OdC) is proposed as a novel measure to characterize the complexity of an undirected graph, or network. While both for regular lattices and fully connected networks OdC is zero, it takes a moderately low value for a random graph and shows high values for apparently complex structures as scale-free networks and hierarchical trees. The OdC approach is applied to the Helicobacter pylori protein interaction network and randomly rewired surrogates.

Understanding global health governance as a complex adaptive system.

PubMed

Hill, Peter S

2011-01-01

The transition from international to global health reflects the rapid growth in the numbers and nature of stakeholders in health, as well as the constant change embodied in the process of globalisation itself. This paper argues that global health governance shares the characteristics of complex adaptive systems, with its multiple and diverse players, and their polyvalent and constantly evolving relationships, and rich and dynamic interactions. The sheer quantum of initiatives, the multiple networks through which stakeholders (re)configure their influence, the range of contexts in which development for health is played out - all compound the complexity of this system. This paper maps out the characteristics of complex adaptive systems as they apply to global health governance, linking them to developments in the past two decades, and the multiple responses to these changes. Examining global health governance through the frame of complexity theory offers insight into the current dynamics of governance, and while providing a framework for making meaning of the whole, opens up ways of accessing this complexity through local points of engagement.

Unraveling the CHIP:Hsp70 complex as an information processor for protein quality control.

PubMed

VanPelt, Jamie; Page, Richard C

2017-02-01

The CHIP:Hsp70 complex stands at the crossroads of the cellular protein quality control system. Hsp70 facilitates active refolding of misfolded client proteins, while CHIP directs ubiquitination of misfolded client proteins bound to Hsp70. The direct competition between CHIP and Hsp70 for the fate of misfolded proteins leads to the question: how does the CHIP:Hsp70 complex execute triage decisions that direct misfolded proteins for either refolding or degradation? The current body of literature points toward action of the CHIP:Hsp70 complex as an information processor that takes inputs in the form of client folding state, dynamics, and posttranslational modifications, then outputs either refolded or ubiquitinated client proteins. Herein we examine the CHIP:Hsp70 complex beginning with the structure and function of CHIP and Hsp70, followed by an examination of recent studies of the interactions and dynamics of the CHIP:Hsp70 complex. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthesis, crystal structure, antimicrobial activity and DNA-binding of hydrogen-bonded proton-transfer complex of 2,6-diaminopyridine with picric acid.

PubMed

Khan, Ishaat M; Ahmad, Afaq; Ullah, M F

2011-04-04

A proton-transfer (charge transfer) complex formed on the reaction between 2,6-diaminopyridine (donor) and picric acid (acceptor) was synthesized and characterized by FTIR, (1)H NMR, thermal and elemental analysis. The crystal structure determined by single-crystal X-ray diffraction indicates that cation and anion are joined together by strong N(+)-H- -O(-) type hydrogen bonds. The hydrogen-bonded charge transfer (HBCT) complex was screened for its pharmacology such as antimicrobial activity against various fungal and bacterial strains and Calf thymus DNA-binding. The results showed that HBCT complex (100μg/ml) exhibited good antibacterial antifungal activity as that of standard antibiotics Tetracycline and Nystatin. A molecular frame work through H-bonding interactions between neighboring moieties is found to be responsible for high melting point of resulting complex. This has been attributed to the formation of 1:1 HBCT complex. Copyright © 2011 Elsevier B.V. All rights reserved.

An initial physical mechanism in the treatment of neurologic disorders with externally applied pico Tesla magnetic fields.

PubMed

Jacobson, J I; Yamanashi, W S

1995-04-01

The recent clinical studies describing the treatment of some neurological disorders with an externally applied pico Tesla (10(-12) Tesla, or 10(-8) gauss) magnetic field are considered from a physical view point. An equation relating the intrinsic (or rest) energy of a charged particle of mass m with its energy of interaction in an externally applied magnetic field B is presented. The equation represents an initial basic physical interaction as a part of a more complex biological mechanism to explain the therapeutic effects of externally applied magnetic fields in these and other neurologic disorders.

A physical mechanism in the treatment of neurologic disorders with externally applied pico Tesla magnetic fields.

PubMed

Jacobson, J I; Yamanashi, W S

1995-06-01

The clinical studies describing the treatment of some neurological disorders with an externally applied pico Tesla (10R Tesla, or 10(-8) gauss) magnetic field are considered from a physical view point. An equation relating the intrinsic or "rest" energy of a charged particle of mass with its energy of interaction in an externally applied magnetic field B is presented. The equation is proposed to represent an initial basic physical interaction as a part of a more complex biological mechanism to explain the therapeutic effects of externally applied magnetic fields in these and other neurologic disorders.

Systematic identification of an integrative network module during senescence from time-series gene expression.

PubMed

Park, Chihyun; Yun, So Jeong; Ryu, Sung Jin; Lee, Soyoung; Lee, Young-Sam; Yoon, Youngmi; Park, Sang Chul

2017-03-15

Cellular senescence irreversibly arrests growth of human diploid cells. In addition, recent studies have indicated that senescence is a multi-step evolving process related to important complex biological processes. Most studies analyzed only the genes and their functions representing each senescence phase without considering gene-level interactions and continuously perturbed genes. It is necessary to reveal the genotypic mechanism inferred by affected genes and their interaction underlying the senescence process. We suggested a novel computational approach to identify an integrative network which profiles an underlying genotypic signature from time-series gene expression data. The relatively perturbed genes were selected for each time point based on the proposed scoring measure denominated as perturbation scores. Then, the selected genes were integrated with protein-protein interactions to construct time point specific network. From these constructed networks, the conserved edges across time point were extracted for the common network and statistical test was performed to demonstrate that the network could explain the phenotypic alteration. As a result, it was confirmed that the difference of average perturbation scores of common networks at both two time points could explain the phenotypic alteration. We also performed functional enrichment on the common network and identified high association with phenotypic alteration. Remarkably, we observed that the identified cell cycle specific common network played an important role in replicative senescence as a key regulator. Heretofore, the network analysis from time series gene expression data has been focused on what topological structure was changed over time point. Conversely, we focused on the conserved structure but its context was changed in course of time and showed it was available to explain the phenotypic changes. We expect that the proposed method will help to elucidate the biological mechanism unrevealed by the existing approaches.

Microbial endocrinology: Host-microbiota neuroendocrine interactions influencing brain and behavior.

PubMed

Lyte, Mark

2014-01-01

The ability of microorganisms, whether present as commensals within the microbiota or introduced as part of a therapeutic regimen, to influence behavior has been demonstrated by numerous laboratories over the last few years. Our understanding of the mechanisms that are responsible for microbiota-gut-brain interactions is, however, lacking. The complexity of the microbiota is, of course, a contributing factor. Nonetheless, while microbiologists approaching the issue of microbiota-gut-brain interactions in the behavior well recognize such complexity, what is often overlooked is the equal complexity of the host neurophysiological system, especially within the gut which is differentially innervated by the enteric nervous system. As such, in the search for common mechanisms by which the microbiota may influence behavior one may look for mechanisms which are shared by both host and microbiota. Such interkingdom signaling can be found in the shared production of neurochemical mediators that are found in both eukaryotes and prokaryotes. The study of the production and recognition of neurochemicals that are exactly the same in structure to those produced in the vertebrate organisms is known as microbial endocrinology. The examination of the microbiota from the vantage point of host-microbiota neuroendocrine interactions cannot only identify new microbial endocrinology-based mechanisms by which the microbiota can influence host behavior, but also lead to the design of interventions in which the composition of the microbiota may be modulated in order to achieve a specific microbial endocrinology-based profile beneficial to overall host behavior.

The estimation of H-bond and metal ion-ligand interaction energies in the G-Quadruplex ⋯ Mn+ complexes

NASA Astrophysics Data System (ADS)

Mostafavi, Najmeh; Ebrahimi, Ali

2018-06-01

In order to characterize various interactions in the G-quadruplex ⋯ Mn+ (G-Q ⋯ Mn+) complexes, the individual H-bond (EHB) and metal ion-ligand interaction (EMO) energies have been estimated using the electron charge densities (ρs) calculated at the X ⋯ H (X = N and O) and Mn+ ⋯ O (Mn+ is an alkaline, alkaline earth and transition metal ion) bond critical points (BCPs) obtained from the atoms in molecules (AIM) analysis. The estimated values of EMO and EHB were evaluated using the structural parameters, results of natural bond orbital analysis (NBO), aromaticity indexes and atomic charges. The EMO value increase with the ratio of ionic charge to radius, e/r, where a linear correlation is observed between EMO and e/r (R = 0.97). Meaningful relationships are also observed between EMO and indexes used for aromaticity estimation. The ENH value is higher than EOH in the complexes; this is in complete agreement with the trend of N⋯Hsbnd N and O⋯Hsbnd N angles, the E (2) value of nN → σ*NH and nO → σ*NH interactions and the difference between the natural charges on the H-bonded atom and the hydrogen atom of guanine (Δq). In general, the O1MO2 angle becomes closer to 109.5° with the increase in EMO and decrease in EHB in the presence of metal ion.

The MAGIC Touch: Combining MAGIC-Pointing with a Touch-Sensitive Mouse

NASA Astrophysics Data System (ADS)

Drewes, Heiko; Schmidt, Albrecht

In this paper, we show how to use the combination of eye-gaze and a touch-sensitive mouse to ease pointing tasks in graphical user interfaces. A touch of the mouse positions the mouse pointer at the current gaze position of the user. Thus, the pointer is always at the position where the user expects it on the screen. This approach changes the user experience in tasks that include frequent switching between keyboard and mouse input (e.g. working with spreadsheets). In a user study, we compared the touch-sensitive mouse with a traditional mouse and observed speed improvements for pointing tasks on complex backgrounds. For pointing task on plain backgrounds, performances with both devices were similar, but users perceived the gaze-sensitive interaction of the touch-sensitive mouse as being faster and more convenient. Our results show that using a touch-sensitive mouse that positions the pointer on the user’s gaze position reduces the need for mouse movements in pointing tasks enormously.

Unified Numerical Solver for Device Metastabilities in CdTe Thin-Film PV

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

Vasileska, Dragica

Thin-film modules of all technologies often suffer from performance degradation over time. Some of the performance changes are reversible and some are not, which makes deployment, testing, and energy-yield prediction more challenging. Manufacturers de-vote significant empirical efforts to study these phenomena and to improve semiconduc-tor device stability. Still, understanding the underlying reasons of these instabilities re-mains clouded due to the lack of ability to characterize materials at atomistic levels and the lack of interpretation from the most fundamental material science. The most com-monly alleged causes of metastability in CdTe device, such as “migration of Cu,” have been investigated rigorously overmore » the past fifteen years. Still, the discussion often ended prematurely with stating observed correlations between stress conditions and changes in atomic profiles of impurities or CV doping concentration. Multiple hypotheses sug-gesting degradation of CdTe solar cell devices due to interaction and evolution of point defects and complexes were proposed, and none of them received strong theoretical or experimental confirmation. It should be noted that atomic impurity profiles in CdTe pro-vide very little intelligence on active doping concentrations. The same elements could form different energy states, which could be either donors or acceptors, depending on their position in crystalline lattice. Defects interact with other extrinsic and intrinsic de-fects; for example, changing the state of an impurity from an interstitial donor to a sub-stitutional acceptor often is accompanied by generation of a compensating intrinsic in-terstitial donor defect. Moreover, all defects, intrinsic and extrinsic, interact with the elec-trical potential and free carriers so that charged defects may drift in the electric field and the local electrical potential affects the formation energy of the point defects. Such complexity of interactions in CdTe makes understanding of temporal changes in device performance even more challenging and a closed solution that can treat the entire sys-tem and its interactions is required.« less

Metastability and reliability of CdTe solar cells

NASA Astrophysics Data System (ADS)

Guo, Da; Brinkman, Daniel; Shaik, Abdul R.; Ringhofer, Christian; Vasileska, Dragica

2018-04-01

Thin-film modules of all technologies often suffer from performance degradation over time. Some of the performance changes are reversible and some are not, which makes deployment, testing, and energy-yield prediction more challenging. Manufacturers devote significant empirical efforts to study these phenomena and to improve semiconductor device stability. Still, understanding the underlying reasons of these instabilities remains clouded due to the lack of ability to characterize materials at atomistic levels and the lack of interpretation from the most fundamental material science. The most commonly alleged causes of metastability in CdTe devices, such as ‘migration of Cu’, have been investigated rigorously over the past fifteen years. Still, the discussion often ended prematurely with stating observed correlations between stress conditions and changes in atomic profiles of impurities or CV doping concentration. Multiple hypotheses suggesting degradation of CdTe solar cell devices due to interaction and evolution of point defects and complexes were proposed, and none of them received strong theoretical or experimental confirmation. It should be noted that atomic impurity profiles in CdTe provide very little intelligence on active doping concentrations. The same elements could form different energy states, which could be either donors or acceptors, depending on their position in crystalline lattice. Defects interact with other extrinsic and intrinsic defects; for example, changing the state of an impurity from an interstitial donor to a substitutional acceptor often is accompanied by generation of a compensating intrinsic interstitial donor defect. Moreover, all defects, intrinsic and extrinsic, interact with the electrical potential and free carriers so that charged defects may drift in the electric field and the local electrical potential affects the formation energy of the point defects. Such complexity of interactions in CdTe makes understanding of temporal changes in device performance even more challenging and a closed solution that can treat the entire system and its interactions is required.

Child-caregiver interaction in two remote Indigenous Australian communities

PubMed Central

Vaughan, Jill; Wigglesworth, Gillian; Loakes, Deborah; Disbray, Samantha; Moses, Karin

2015-01-01

This paper reports on a study in two remote multilingual Indigenous Australian communities: Yakanarra in the Kimberley region of Western Australia and Tennant Creek in the Barkly region of the Northern Territory. In both communities, processes of language shift are underway from a traditional language (Walmajarri and Warumungu, respectively) to a local creole variety (Fitzroy Valley Kriol and Wumpurrarni English, respectively). The study focuses on language input from primary caregivers to a group of preschool children, and on the children's productive language. The study further highlights child-caregiver interactions as a site of importance in understanding the broader processes of language shift. We use longitudinal data from two time-points, approximately 2 years apart, to explore changes in adult input over time and developmental patterns in the children's speech. At both time points, the local creole varieties are the preferred codes of communication for the dyads in this study, although there is some use of the traditional language in both communities. Results show that for measures of turn length (MLT), there are notable differences between the two communities for both the focus children and their caregivers. In Tennant Creek, children and caregivers use longer turns at Time 2, while in Yakanarra the picture is more variable. The two communities also show differing trends in terms of conversational load (MLT ratio). For measures of morphosyntactic complexity (MLU), children and caregivers in Tennant Creek use more complex utterances at Time 2, while caregivers in Yakanarra show less complexity in their language at that time point. The study's findings contribute to providing a more detailed picture of the multilingual practices at Yakanarra and Tennant Creek, with implications for understanding broader processes of language shift. They also elucidate how children's language and linguistic input varies diachronically across time. As such, we contribute to understandings of normative language development for non-Western, non middle-class children in multilingual contexts. PMID:25972828

Dynein and dynactin leverage their bivalent character to form a high-affinity interaction.

PubMed

Siglin, Amanda E; Sun, Shangjin; Moore, Jeffrey K; Tan, Sarah; Poenie, Martin; Lear, James D; Polenova, Tatyana; Cooper, John A; Williams, John C

2013-01-01

Cytoplasmic dynein and dynactin participate in retrograde transport of organelles, checkpoint signaling and cell division. The principal subunits that mediate this interaction are the dynein intermediate chain (IC) and the dynactin p150(Glued); however, the interface and mechanism that regulates this interaction remains poorly defined. Herein, we use multiple methods to show the N-terminus of mammalian dynein IC, residues 10-44, is sufficient for binding p150(Glued). Consistent with this mapping, monoclonal antibodies that antagonize the dynein-dynactin interaction also bind to this region of the IC. Furthermore, double and triple alanine point mutations spanning residues 6 to 19 in the yeast IC homolog, Pac11, produce significant defects in spindle positioning. Using the same methods we show residues 381 to 530 of p150(Glued) form a minimal fragment that binds to the dynein IC. Sedimentation equilibrium experiments indicate that these individual fragments are predominantly monomeric, but admixtures of the IC and p150(Glued) fragments produce a 2:2 complex. This tetrameric complex is sensitive to salt, temperature and pH, suggesting that the binding is dominated by electrostatic interactions. Finally, circular dichroism (CD) experiments indicate that the N-terminus of the IC is disordered and becomes ordered upon binding p150(Glued). Taken together, the data indicate that the dynein-dynactin interaction proceeds through a disorder-to-order transition, leveraging its bivalent-bivalent character to form a high affinity, but readily reversible interaction.

A separable domain of the p150 subunit of human chromatin assembly factor-1 promotes protein and chromosome associations with nucleoli.

PubMed

Smith, Corey L; Matheson, Timothy D; Trombly, Daniel J; Sun, Xiaoming; Campeau, Eric; Han, Xuemei; Yates, John R; Kaufman, Paul D

2014-09-15

Chromatin assembly factor-1 (CAF-1) is a three-subunit protein complex conserved throughout eukaryotes that deposits histones during DNA synthesis. Here we present a novel role for the human p150 subunit in regulating nucleolar macromolecular interactions. Acute depletion of p150 causes redistribution of multiple nucleolar proteins and reduces nucleolar association with several repetitive element-containing loci. Of note, a point mutation in a SUMO-interacting motif (SIM) within p150 abolishes nucleolar associations, whereas PCNA or HP1 interaction sites within p150 are not required for these interactions. In addition, acute depletion of SUMO-2 or the SUMO E2 ligase Ubc9 reduces α-satellite DNA association with nucleoli. The nucleolar functions of p150 are separable from its interactions with the other subunits of the CAF-1 complex because an N-terminal fragment of p150 (p150N) that cannot interact with other CAF-1 subunits is sufficient for maintaining nucleolar chromosome and protein associations. Therefore these data define novel functions for a separable domain of the p150 protein, regulating protein and DNA interactions at the nucleolus. © 2014 Smith et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Electrostatic Interactions in Aminoglycoside-RNA Complexes

PubMed Central

Kulik, Marta; Goral, Anna M.; Jasiński, Maciej; Dominiak, Paulina M.; Trylska, Joanna

2015-01-01

Electrostatic interactions often play key roles in the recognition of small molecules by nucleic acids. An example is aminoglycoside antibiotics, which by binding to ribosomal RNA (rRNA) affect bacterial protein synthesis. These antibiotics remain one of the few valid treatments against hospital-acquired infections by Gram-negative bacteria. It is necessary to understand the amplitude of electrostatic interactions between aminoglycosides and their rRNA targets to introduce aminoglycoside modifications that would enhance their binding or to design new scaffolds. Here, we calculated the electrostatic energy of interactions and its per-ring contributions between aminoglycosides and their primary rRNA binding site. We applied either the methodology based on the exact potential multipole moment (EPMM) or classical molecular mechanics force field single-point partial charges with Coulomb formula. For EPMM, we first reconstructed the aspherical electron density of 12 aminoglycoside-RNA complexes from the atomic parameters deposited in the University at Buffalo Databank. The University at Buffalo Databank concept assumes transferability of electron density between atoms in chemically equivalent vicinities and allows reconstruction of the electron densities from experimental structural data. From the electron density, we then calculated the electrostatic energy of interaction using EPMM. Finally, we compared the two approaches. The calculated electrostatic interaction energies between various aminoglycosides and their binding sites correlate with experimentally obtained binding free energies. Based on the calculated energetic contributions of water molecules mediating the interactions between the antibiotic and rRNA, we suggest possible modifications that could enhance aminoglycoside binding affinity. PMID:25650932

Proteomic Interaction Patterns between Human Cyclins, the Cyclin-Dependent Kinase Ortholog pUL97 and Additional Cytomegalovirus Proteins

PubMed Central

Steingruber, Mirjam; Kraut, Alexandra; Socher, Eileen; Sticht, Heinrich; Reichel, Anna; Stamminger, Thomas; Amin, Bushra; Couté, Yohann; Hutterer, Corina; Marschall, Manfred

2016-01-01

The human cytomegalovirus (HCMV)-encoded cyclin-dependent kinase (CDK) ortholog pUL97 associates with human cyclin B1 and other types of cyclins. Here, the question was addressed whether cyclin interaction of pUL97 and additional viral proteins is detectable by mass spectrometry-based approaches. Proteomic data were validated by coimmunoprecipitation (CoIP), Western blot, in vitro kinase and bioinformatic analyses. Our findings suggest that: (i) pUL97 shows differential affinities to human cyclins; (ii) pUL97 inhibitor maribavir (MBV) disrupts the interaction with cyclin B1, but not with other cyclin types; (iii) cyclin H is identified as a new high-affinity interactor of pUL97 in HCMV-infected cells; (iv) even more viral phosphoproteins, including all known substrates of pUL97, are detectable in the cyclin-associated complexes; and (v) a first functional validation of pUL97-cyclin B1 interaction, analyzed by in vitro kinase assay, points to a cyclin-mediated modulation of pUL97 substrate preference. In addition, our bioinformatic analyses suggest individual, cyclin-specific binding interfaces for pUL97-cyclin interaction, which could explain the different strengths of interactions and the selective inhibitory effect of MBV on pUL97-cyclin B1 interaction. Combined, the detection of cyclin-associated proteins in HCMV-infected cells suggests a complex pattern of substrate phosphorylation and a role of cyclins in the fine-modulation of pUL97 activities. PMID:27548200

Insights into the Hendra virus NTAIL-XD complex: Evidence for a parallel organization of the helical MoRE at the XD surface stabilized by a combination of hydrophobic and polar interactions.

PubMed

Erales, Jenny; Beltrandi, Matilde; Roche, Jennifer; Maté, Maria; Longhi, Sonia

2015-08-01

The Hendra virus is a member of the Henipavirus genus within the Paramyxoviridae family. The nucleoprotein, which consists of a structured core and of a C-terminal intrinsically disordered domain (N(TAIL)), encapsidates the viral genome within a helical nucleocapsid. N(TAIL) partly protrudes from the surface of the nucleocapsid being thus capable of interacting with the C-terminal X domain (XD) of the viral phosphoprotein. Interaction with XD implies a molecular recognition element (MoRE) that is located within N(TAIL) residues 470-490, and that undergoes α-helical folding. The MoRE has been proposed to be embedded in the hydrophobic groove delimited by helices α2 and α3 of XD, although experimental data could not discriminate between a parallel and an antiparallel orientation of the MoRE. Previous studies also showed that if the binding interface is enriched in hydrophobic residues, charged residues located close to the interface might play a role in complex formation. Here, we targeted for site directed mutagenesis two acidic and two basic residues within XD and N(TAIL). ITC studies showed that electrostatics plays a crucial role in complex formation and pointed a parallel orientation of the MoRE as more likely. Further support for a parallel orientation was afforded by SAXS studies that made use of two chimeric constructs in which XD and the MoRE were covalently linked to each other. Altogether, these studies unveiled the multiparametric nature of the interactions established within this complex and contribute to shed light onto the molecular features of protein interfaces involving intrinsically disordered regions. Copyright © 2015 Elsevier B.V. All rights reserved.

Optimization of binding electrostatics: Charge complementarity in the barnase-barstar protein complex

PubMed Central

lee, Lee-Peng; Tidor, Bruce

2001-01-01

Theoretical and experimental studies have shown that the large desolvation penalty required for polar and charged groups frequently precludes their involvement in electrostatic interactions that contribute strongly to net stability in the folding or binding of proteins in aqueous solution near room temperature. We have previously developed a theoretical framework for computing optimized electrostatic interactions and illustrated use of the algorithm with simplified geometries. Given a receptor and model assumptions, the method computes the ligand-charge distribution that provides the most favorable balance of desolvation and interaction effects on binding. In this paper the method has been extended to treat complexes using actual molecular shapes. The barnase-barstar protein complex was investigated with barnase treated as a target receptor. The atomic point charges of barstar were varied to optimize the electrostatic binding free energy. Barnase and natural barstar form a tight complex (Kd ∼ 10−14 M) with many charged and polar groups near the interface that make this a particularly relevant system for investigating the role of electrostatic effects on binding. The results show that sets of barstar charges (resulting from optimization with different constraints) can be found that give rise to relatively large predicted improvements in electrostatic binding free energy. Principles for enhancing the effect of electrostatic interactions in molecular binding in aqueous environments are discussed in light of the optima. Our findings suggest that, in general, the enhancements in electrostatic binding free energy resulting from modification of polar and charged groups can be substantial. Moreover, a recently proposed definition of electrostatic complementarity is shown to be a useful tool for examining binding interfaces. Finally, calculational results suggest that wild-type barstar is closer to being affinity optimized than is barnase for their mutual binding, consistent with the known roles of these proteins. PMID:11266622

A spectroscopic study of phenylbutazone and aspirin bound to serum albumin in rheumatoid diseases

NASA Astrophysics Data System (ADS)

Maciążek-Jurczyk, M.; Sułkowska, A.; Bojko, B.; Równicka-Zubik, J.; Sułkowski, W. W.

2011-11-01

Interaction of phenylbutazone (PBZ) and aspirin (ASA), two drugs recommended in rheumatoid diseases (RDs), when binding to human (HSA) and bovine (BSA) serum albumins, has been studied by quenching of fluorescence and proton nuclear magnetic resonance ( 1HNMR) techniques. On the basis of spectrofluorescence measurements high affinity binding sites of PBZ and ASA on albumin as well as their interaction within the binding sites were described. A low affinity binding site has been studied by proton nuclear magnetic resonance spectroscopy. Using fluorescence spectroscopy the location of binding site in serum albumin (SA) for PBZ and ASA was found. Association constants Ka were determined for binary (i.e. PBZ-SA and ASA-SA) and ternary complexes (i.e. PBZ-[ASA]-SA and ASA-[PBZ]-SA). PBZ and ASA change the affinity of each other to the binding site in serum albumin (SA). The presence of ASA causes the increase of association constants KaI of PBZ-SA complex. Similarly, PBZ influences KaI of ASA-SA complex. This phenomenon shows that the strength of binding and the stability of the complexes increase in the presence of the second drug. The decrease of KaII values suggests that the competition between PBZ and ASA in binding to serum albumin in the second class of binding sites occurs. The analysis of 1HNMR spectral parameters i.e. changes of chemical shifts and relaxation times of the drug indicate that the presence of ASA weakens the interaction of PBZ with albumin. Similarly PBZ weakens the interaction of ASA with albumin. This conclusion points to the necessity of using a monitoring therapy owning to the possible increase of uncontrolled toxic effects.

Evaluating the Free Energies of Solvation and Electronic Structures of Lithium-Ion Battery Electrolytes.

PubMed

Shakourian-Fard, Mehdi; Kamath, Ganesh; Sankaranarayanan, Subramanian K R S

2016-09-19

Adaptive biasing force molecular dynamics simulations and density functional theory calculations were performed to understand the interaction of Li(+) with pure carbonates and ethylene carbonate (EC)-based binary mixtures. The most favorable Li carbonate cluster configurations obtained from molecular dynamics simulations were subjected to detailed structural and thermochemistry calculations on the basis of the M06-2X/6-311++G(d,p) level of theory. We report the ranking of these electrolytes on the basis of the free energies of Li-ion solvation in carbonates and EC-based mixtures. A strong local tetrahedral order involving four carbonates around the Li(+) was seen in the first solvation shell. Thermochemistry calculations revealed that the enthalpy of solvation and the Gibbs free energy of solvation of the Li(+) ion with carbonates are negative and suggested the ion-carbonate complexation process to be exothermic and spontaneous. Natural bond orbital analysis indicated that Li(+) interacts with the lone pairs of electrons on the carbonyl oxygen atom in the primary solvation sphere. These interactions lead to an increase in the carbonyl (C=O) bond lengths, as evidenced by a redshift in the vibrational frequencies [ν(C=O)] and a decrease in the electron density values at the C=O bond critical points in the primary solvation sphere. Quantum theory of atoms in molecules, localized molecular orbital energy decomposition analysis (LMO-EDA), and noncovalent interaction plots revealed the electrostatic nature of the Li(+) ion interactions with the carbonyl oxygen atoms in these complexes. On the basis of LMO-EDA, the strongest attractive interaction in these complexes was found to be the electrostatic interaction followed by polarization, dispersion, and exchange interactions. Overall, our calculations predicted EC and a binary mixture of EC/dimethyl carbonate to be appropriate electrolytes for Li-ion batteries, which complies with experiments and other theoretical results. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Decay of Complex-Time Determinantal and Pfaffian Correlation Functionals in Lattices

NASA Astrophysics Data System (ADS)

Aza, N. J. B.; Bru, J.-B.; de Siqueira Pedra, W.

2018-04-01

We supplement the determinantal and Pfaffian bounds of Sims and Warzel (Commun Math Phys 347:903-931, 2016) for many-body localization of quasi-free fermions, by considering the high dimensional case and complex-time correlations. Our proof uses the analyticity of correlation functions via the Hadamard three-line theorem. We show that the dynamical localization for the one-particle system yields the dynamical localization for the many-point fermionic correlation functions, with respect to the Hausdorff distance in the determinantal case. In Sims and Warzel (2016), a stronger notion of decay for many-particle configurations was used but only at dimension one and for real times. Considering determinantal and Pfaffian correlation functionals for complex times is important in the study of weakly interacting fermions.

Identification of vortices in complex flows

NASA Astrophysics Data System (ADS)

Chakraborty, P.; Balachandar, S.; Adrian, R. J.

2007-12-01

Dating back to Leonardo da Vinci's famous sketches of vortices in turbulent flows, fluid dynamicists for over five centuries have continued to visualize and interpret complex flows in terms of motion of vortices. Nevertheless, much debate surrounds the question of how to unambiguously define vortices in complex flows. This debate has resulted in the availability of many vortex identification criteria---mathematical statements of what constitutes a vortex. Here we review the popularly used local or point- wise vortex identification criteria. Based on local flow kinematics, we describe a unified framework to interpret the similarities and differences in the usage of these criteria. We discuss the limitations on the applicability of these criteria when there is a significant component of vortex interactions. Finally, we provide guidelines for applying these criteria to geophysical flows.

Decay of Complex-Time Determinantal and Pfaffian Correlation Functionals in Lattices

NASA Astrophysics Data System (ADS)

Aza, N. J. B.; Bru, J.-B.; de Siqueira Pedra, W.

2018-06-01

We supplement the determinantal and Pfaffian bounds of Sims and Warzel (Commun Math Phys 347:903-931, 2016) for many-body localization of quasi-free fermions, by considering the high dimensional case and complex-time correlations. Our proof uses the analyticity of correlation functions via the Hadamard three-line theorem. We show that the dynamical localization for the one-particle system yields the dynamical localization for the many-point fermionic correlation functions, with respect to the Hausdorff distance in the determinantal case. In Sims and Warzel (2016), a stronger notion of decay for many-particle configurations was used but only at dimension one and for real times. Considering determinantal and Pfaffian correlation functionals for complex times is important in the study of weakly interacting fermions.

Liquid-gas phase transitions and C K symmetry in quantum field theories

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

Nishimura, Hiromichi; Ogilvie, Michael C.; Pangeni, Kamal

A general field-theoretic framework for the treatment of liquid-gas phase transitions is developed. Starting from a fundamental four-dimensional field theory at nonzero temperature and density, an effective three-dimensional field theory is derived. The effective field theory has a sign problem at finite density. Although finite density explicitly breaks charge conjugation C , there remains a symmetry under C K , where K is complex conjugation. Here, we consider four models: relativistic fermions, nonrelativistic fermions, static fermions and classical particles. The interactions are via an attractive potential due to scalar field exchange and a repulsive potential due to massive vector exchange.more » The field-theoretic representation of the partition function is closely related to the equivalence of the sine-Gordon field theory with a classical gas. The thermodynamic behavior is extracted from C K -symmetric complex saddle points of the effective field theory at tree level. In the cases of nonrelativistic fermions and classical particles, we find complex saddle point solutions but no first-order transitions, and neither model has a ground state at tree level. The relativistic and static fermions show a liquid-gas transition at tree level in the effective field theory. The liquid-gas transition, when it occurs, manifests as a first-order line at low temperature and high density, terminated by a critical end point. The mass matrix controlling the behavior of correlation functions is obtained from fluctuations around the saddle points. Due to the C K symmetry of the models, the eigenvalues of the mass matrix are not always real but can be complex. This then leads to the existence of disorder lines, which mark the boundaries where the eigenvalues go from purely real to complex. The regions where the mass matrix eigenvalues are complex are associated with the critical line. In the case of static fermions, a powerful duality between particles and holes allows for the analytic determination of both the critical line and the disorder lines. Depending on the values of the parameters, either zero, one, or two disorder lines are found. Our numerical results for relativistic fermions give a very similar picture.« less

Liquid-gas phase transitions and C K symmetry in quantum field theories

DOE PAGES

Nishimura, Hiromichi; Ogilvie, Michael C.; Pangeni, Kamal

2017-04-04

A general field-theoretic framework for the treatment of liquid-gas phase transitions is developed. Starting from a fundamental four-dimensional field theory at nonzero temperature and density, an effective three-dimensional field theory is derived. The effective field theory has a sign problem at finite density. Although finite density explicitly breaks charge conjugation C , there remains a symmetry under C K , where K is complex conjugation. Here, we consider four models: relativistic fermions, nonrelativistic fermions, static fermions and classical particles. The interactions are via an attractive potential due to scalar field exchange and a repulsive potential due to massive vector exchange.more » The field-theoretic representation of the partition function is closely related to the equivalence of the sine-Gordon field theory with a classical gas. The thermodynamic behavior is extracted from C K -symmetric complex saddle points of the effective field theory at tree level. In the cases of nonrelativistic fermions and classical particles, we find complex saddle point solutions but no first-order transitions, and neither model has a ground state at tree level. The relativistic and static fermions show a liquid-gas transition at tree level in the effective field theory. The liquid-gas transition, when it occurs, manifests as a first-order line at low temperature and high density, terminated by a critical end point. The mass matrix controlling the behavior of correlation functions is obtained from fluctuations around the saddle points. Due to the C K symmetry of the models, the eigenvalues of the mass matrix are not always real but can be complex. This then leads to the existence of disorder lines, which mark the boundaries where the eigenvalues go from purely real to complex. The regions where the mass matrix eigenvalues are complex are associated with the critical line. In the case of static fermions, a powerful duality between particles and holes allows for the analytic determination of both the critical line and the disorder lines. Depending on the values of the parameters, either zero, one, or two disorder lines are found. Our numerical results for relativistic fermions give a very similar picture.« less

Surfing on Protein Waves: Proteophoresis as a Mechanism for Bacterial Genome Partitioning

NASA Astrophysics Data System (ADS)

Walter, J.-C.; Dorignac, J.; Lorman, V.; Rech, J.; Bouet, J.-Y.; Nollmann, M.; Palmeri, J.; Parmeggiani, A.; Geniet, F.

2017-07-01

Efficient bacterial chromosome segregation typically requires the coordinated action of a three-component machinery, fueled by adenosine triphosphate, called the partition complex. We present a phenomenological model accounting for the dynamic activity of this system that is also relevant for the physics of catalytic particles in active environments. The model is obtained by coupling simple linear reaction-diffusion equations with a proteophoresis, or "volumetric" chemophoresis, force field that arises from protein-protein interactions and provides a physically viable mechanism for complex translocation. This minimal description captures most known experimental observations: dynamic oscillations of complex components, complex separation, and subsequent symmetrical positioning. The predictions of our model are in phenomenological agreement with and provide substantial insight into recent experiments. From a nonlinear physics view point, this system explores the active separation of matter at micrometric scales with a dynamical instability between static positioning and traveling wave regimes triggered by the dynamical spontaneous breaking of rotational symmetry.

Ab initio molecular orbital calculations on the associated complexes of lithium cyanide with ammonia

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

Mohandas, P.; Shivaglal, M.C.; Chandrasekhar, J.

Ab initio molecular orbital (MO) calculations with the 3-21G and 6-31G basis sets are carried out on a series of complexes of NH{sub 3} with Li{sup +}, C{triple_bond}N{sup -}, LiCN, and its isomer LiNC. The BSSE-corrected interaction energies, geometrical parameters, internal force constants, and harmonic vibrational frequencies are evaluated for 15 species. Complexes with trifurcated (C{sub 3v}) structures are calculated to be saddle points on the potential energy surfaces and have one imaginary frequency each. Calculated energies, geometrical parameters, internal force constants, and harmonic vibrational frequencies of the various species considered are discussed in terms of the nature of associationmore » of LiCN with ammonia. The vibrational frequencies of the relevant complexed species are compared with the experimental frequencies reported earlier for solutions of lithium cyanide in liquid ammonia. 40 refs., 1 fig., 4 tabs.« less

Does job complexity mitigate the negative effect of emotion-rule dissonance on employee burnout?

PubMed Central

Kubicek, Bettina; Korunka, Christian

2015-01-01

ABSTRACT In interactions with clients or patients, human service workers are at risk of experiencing discrepancies between felt and organizationally mandated emotions (i.e. emotion-rule dissonance). Given the documented detrimental effects of such discrepancies on employee strain, the present study investigated whether job complexity mitigates the relation between emotion-rule dissonance and employee burnout using data from a two-wave panel study of eldercare workers (N = 583, 16-month time lag). Structural equation modelling revealed that emotion-rule dissonance at Time 1 preceded emotional exhaustion and depersonalization at Time 2. Beyond that, employees whose work offered job complexity were found to suffer less from emotional exhaustion and depersonalization when encountering discrepancies between felt and stipulated emotions compared to employees who conducted noncomplex work. Thus, designing complex tasks appears to be a crucial starting point for alleviating employee burnout in jobs that provoke emotion-rule dissonance. PMID:26681818

High-resolution method for evolving complex interface networks

NASA Astrophysics Data System (ADS)

Pan, Shucheng; Hu, Xiangyu Y.; Adams, Nikolaus A.

2018-04-01

In this paper we describe a high-resolution transport formulation of the regional level-set approach for an improved prediction of the evolution of complex interface networks. The novelty of this method is twofold: (i) construction of local level sets and reconstruction of a global level set, (ii) local transport of the interface network by employing high-order spatial discretization schemes for improved representation of complex topologies. Various numerical test cases of multi-region flow problems, including triple-point advection, single vortex flow, mean curvature flow, normal driven flow, dry foam dynamics and shock-bubble interaction show that the method is accurate and suitable for a wide range of complex interface-network evolutions. Its overall computational cost is comparable to the Semi-Lagrangian regional level-set method while the prediction accuracy is significantly improved. The approach thus offers a viable alternative to previous interface-network level-set method.

Electronic structure of the [MNH2]+ (M = Sc-Cu) complexes.

PubMed

Hendrickx, Marc F A; Clima, Sergiu

2006-11-23

B3LYP geometry optimizations for the [MNH2]+ complexes of the first-row transition metal cations (Sc+-Cu+) were performed. Without any exception the ground states of these unsaturated amide complexes were calculated to possess planar geometries. CASPT2 binding energies that were corrected for zero-point energies and including relativistic effects show a qualitative trend across the series that closely resembles the experimental observations. The electronic structures for the complexes of the early and middle transition metal cations (Sc+-Co+) differ from the electronic structures derived for the complexes of the late transition metal cations (Ni+ and Cu+). For the former complexes the relative higher position of the 3d orbitals above the singly occupied 2p(pi) HOMO of the uncoordinated NH2 induces an electron transfer from the 3d shell to 2p(pi). The stabilization of the 3d orbitals from the left to the right along the first-row transition metal series causes these orbitals to become situated below the HOMO of the NH2 ligand for Ni+ and Cu+, preventing a transfer from occurring in the [MNH2]+ complexes of these metal cations. Analysis of the low-lying states of the amide complexes revealed a rather unique characteristic of their electronic structures that was found across the entire series. Rather exceptionally for the whole of chemistry, pi-type interactions were calculated to be stronger than the corresponding sigma-type interactions. The origin of this extraordinary behavior can be ascribed to the low-lying sp2 lone pair orbital of the NH2 ligand with respect to the 3d level.

Evaluation of pharmacotherapy complexity in residents of long-term care facilities: a cross-sectional descriptive study.

PubMed

Alves-Conceição, Vanessa; Silva, Daniel Tenório da; Santana, Vanessa Lima de; Santos, Edileide Guimarães Dos; Santos, Lincoln Marques Cavalcante; Lyra, Divaldo Pereira de

2017-07-25

Polypharmacy is a reality in long-term care facilities. However, number of medications used by the patient should not be the only predictor of a complex pharmacotherapy. Although the level of complexity of pharmacotherapy is considered an important factor that may lead to side effects, there are few studies in this field. The aim of this study was to evaluate the complexity of pharmacotherapy in residents of three long-term care facilities. A cross-sectional study was performed to evaluate the complexity of pharmacotherapy using the protocols laid out in the Medication Regimen Complexity Index instrument in three long-term care facilities in northeastern Brazil. As a secondary result, potential drug interactions, potentially inappropriate medications, medication duplication, and polypharmacy were evaluated. After the assessment, the association among these variables and the Medication Regimen Complexity Index was performed. In this study, there was a higher prevalence of women (64.4%) with a high mean age among the study population of 81.8 (±9.7) years. The complexity of pharmacotherapy obtained a mean of 15.1 points (±9.8), with a minimum of 2 and a maximum of 59. The highest levels of complexity were associated with dose frequency, with a mean of 5.5 (±3.6), followed by additional instructions of use averaging 4.9 (±3.7) and by the dosage forms averaging 4.6 (±3.0). The present study evaluated some factors that complicate the pharmacotherapy of geriatric patients. Although polypharmacy was implicated as a factor directly related to complexity, other indicators such as drug interactions, potentially inappropriate medications, and therapeutic duplication can also make the use of pharmacotherapy in such patients more difficult.

Binding thermodynamics discriminates fragments from druglike compounds: a thermodynamic description of fragment-based drug discovery.

PubMed

Williams, Glyn; Ferenczy, György G; Ulander, Johan; Keserű, György M

2017-04-01

Small is beautiful - reducing the size and complexity of chemical starting points for drug design allows better sampling of chemical space, reveals the most energetically important interactions within protein-binding sites and can lead to improvements in the physicochemical properties of the final drug. The impact of fragment-based drug discovery (FBDD) on recent drug discovery projects and our improved knowledge of the structural and thermodynamic details of ligand binding has prompted us to explore the relationships between ligand-binding thermodynamics and FBDD. Information on binding thermodynamics can give insights into the contributions to protein-ligand interactions and could therefore be used to prioritise compounds with a high degree of specificity in forming key interactions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Analysis of the binding interaction in uric acid - Human hemoglobin system by spectroscopic techniques

NASA Astrophysics Data System (ADS)

Makarska-Bialokoz, Magdalena

2017-05-01

The binding interaction between human hemoglobin and uric acid has been studied for the first time, by UV-vis absorption and steady-state, synchronous and three-dimensional fluorescence techniques. Characteristic effects observed for human hemoglobin intrinsic fluorescence during interaction with uric acid at neutral pH point at the formation of stacking non-covalent and non-fluorescent complexes. All the calculated parameters, the binding, fluorescence quenching and bimolecular quenching rate constants, as well as Förster resonance energy transfer parameters confirm the existence of static quenching. The results of synchronous fluorescence measurements indicate that the fluorescence quenching of human hemoglobin originates both from Trp and Tyr residues and that the addition of uric acid could significantly hinder the physiological functions of human hemoglobin.

Mapping complex traits as a dynamic system

PubMed Central

Sun, Lidan; Wu, Rongling

2017-01-01

Despite increasing emphasis on the genetic study of quantitative traits, we are still far from being able to chart a clear picture of their genetic architecture, given an inherent complexity involved in trait formation. A competing theory for studying such complex traits has emerged by viewing their phenotypic formation as a “system” in which a high-dimensional group of interconnected components act and interact across different levels of biological organization from molecules through cells to whole organisms. This system is initiated by a machinery of DNA sequences that regulate a cascade of biochemical pathways to synthesize endophenotypes and further assemble these endophenotypes toward the end-point phenotype in virtue of various developmental changes. This review focuses on a conceptual framework for genetic mapping of complex traits by which to delineate the underlying components, interactions and mechanisms that govern the system according to biological principles and understand how these components function synergistically under the control of quantitative trait loci (QTLs) to comprise a unified whole. This framework is built by a system of differential equations that quantifies how alterations of different components lead to the global change of trait development and function, and provides a quantitative and testable platform for assessing the multiscale interplay between QTLs and development. The method will enable geneticists to shed light on the genetic complexity of any biological system and predict, alter or engineer its physiological and pathological states. PMID:25772476

TIGER: A user-friendly interactive grid generation system for complicated turbomachinery and axis-symmetric configurations

NASA Technical Reports Server (NTRS)

Shih, Ming H.; Soni, Bharat K.

1993-01-01

The issue of time efficiency in grid generation is addressed by developing a user friendly graphical interface for interactive/automatic construction of structured grids around complex turbomachinery/axis-symmetric configurations. The accuracy of geometry modeling and its fidelity is accomplished by adapting the nonuniform rational b-spline (NURBS) representation. A customized interactive grid generation code, TIGER, has been developed to facilitate the grid generation process for complicated internal, external, and internal-external turbomachinery fields simulations. The FORMS Library is utilized to build user-friendly graphical interface. The algorithm allows a user to redistribute grid points interactively on curves/surfaces using NURBS formulation with accurate geometric definition. TIGER's features include multiblock, multiduct/shroud, multiblade row, uneven blade count, and patched/overlapping block interfaces. It has been applied to generate grids for various complicated turbomachinery geometries, as well as rocket and missile configurations.

Discovery of a small-molecule inhibitor of Dvl-CXXC5 interaction by computational approaches

NASA Astrophysics Data System (ADS)

Ma, Songling; Choi, Jiwon; Jin, Xuemei; Kim, Hyun-Yi; Yun, Ji-Hye; Lee, Weontae; Choi, Kang-Yell; No, Kyoung Tai

2018-05-01

The Wnt/β-catenin signaling pathway plays a significant role in the control of osteoblastogenesis and bone formation. CXXC finger protein 5 (CXXC5) has been recently identified as a negative feedback regulator of osteoblast differentiation through a specific interaction with Dishevelled (Dvl) protein. It was reported that targeting the Dvl-CXXC5 interaction could be a novel anabolic therapeutic target for osteoporosis. In this study, complex structure of Dvl PDZ domain and CXXC5 peptide was simulated with molecular dynamics (MD). Based on the structural analysis of binding modes of MD-simulated Dvl PDZ domain with CXXC5 peptide and crystal Dvl PDZ domain with synthetic peptide-ligands, we generated two different pharmacophore models and applied pharmacophore-based virtual screening to discover potent inhibitors of the Dvl-CXXC5 interaction for the anabolic therapy of osteoporosis. Analysis of 16 compounds selected by means of a virtual screening protocol yielded four compounds that effectively disrupted the Dvl-CXXC5 interaction in the fluorescence polarization assay. Potential compounds were validated by fluorescence spectroscopy and nuclear magnetic resonance. We successfully identified a highly potent inhibitor, BMD4722, which directly binds to the Dvl PDZ domain and disrupts the Dvl-CXXC5 interaction. Overall, CXXC5-Dvl PDZ domain complex based pharmacophore combined with various traditional and simple computational methods is a promising approach for the development of modulators targeting the Dvl-CXXC5 interaction, and the potent inhibitor BMD4722 could serve as a starting point to discover or design more potent and specific the Dvl-CXXC5 interaction disruptors.

Discovery of a small-molecule inhibitor of Dvl-CXXC5 interaction by computational approaches.

PubMed

Ma, Songling; Choi, Jiwon; Jin, Xuemei; Kim, Hyun-Yi; Yun, Ji-Hye; Lee, Weontae; Choi, Kang-Yell; No, Kyoung Tai

2018-05-01

The Wnt/β-catenin signaling pathway plays a significant role in the control of osteoblastogenesis and bone formation. CXXC finger protein 5 (CXXC5) has been recently identified as a negative feedback regulator of osteoblast differentiation through a specific interaction with Dishevelled (Dvl) protein. It was reported that targeting the Dvl-CXXC5 interaction could be a novel anabolic therapeutic target for osteoporosis. In this study, complex structure of Dvl PDZ domain and CXXC5 peptide was simulated with molecular dynamics (MD). Based on the structural analysis of binding modes of MD-simulated Dvl PDZ domain with CXXC5 peptide and crystal Dvl PDZ domain with synthetic peptide-ligands, we generated two different pharmacophore models and applied pharmacophore-based virtual screening to discover potent inhibitors of the Dvl-CXXC5 interaction for the anabolic therapy of osteoporosis. Analysis of 16 compounds selected by means of a virtual screening protocol yielded four compounds that effectively disrupted the Dvl-CXXC5 interaction in the fluorescence polarization assay. Potential compounds were validated by fluorescence spectroscopy and nuclear magnetic resonance. We successfully identified a highly potent inhibitor, BMD4722, which directly binds to the Dvl PDZ domain and disrupts the Dvl-CXXC5 interaction. Overall, CXXC5-Dvl PDZ domain complex based pharmacophore combined with various traditional and simple computational methods is a promising approach for the development of modulators targeting the Dvl-CXXC5 interaction, and the potent inhibitor BMD4722 could serve as a starting point to discover or design more potent and specific the Dvl-CXXC5 interaction disruptors.

Food Web Designer: a flexible tool to visualize interaction networks.

PubMed

Sint, Daniela; Traugott, Michael

Species are embedded in complex networks of ecological interactions and assessing these networks provides a powerful approach to understand what the consequences of these interactions are for ecosystem functioning and services. This is mandatory to develop and evaluate strategies for the management and control of pests. Graphical representations of networks can help recognize patterns that might be overlooked otherwise. However, there is a lack of software which allows visualizing these complex interaction networks. Food Web Designer is a stand-alone, highly flexible and user friendly software tool to quantitatively visualize trophic and other types of bipartite and tripartite interaction networks. It is offered free of charge for use on Microsoft Windows platforms. Food Web Designer is easy to use without the need to learn a specific syntax due to its graphical user interface. Up to three (trophic) levels can be connected using links cascading from or pointing towards the taxa within each level to illustrate top-down and bottom-up connections. Link width/strength and abundance of taxa can be quantified, allowing generating fully quantitative networks. Network datasets can be imported, saved for later adjustment and the interaction webs can be exported as pictures for graphical display in different file formats. We show how Food Web Designer can be used to draw predator-prey and host-parasitoid food webs, demonstrating that this software is a simple and straightforward tool to graphically display interaction networks for assessing pest control or any other type of interaction in both managed and natural ecosystems from an ecological network perspective.

Discovery of a small-molecule inhibitor of Dvl-CXXC5 interaction by computational approaches

NASA Astrophysics Data System (ADS)

Ma, Songling; Choi, Jiwon; Jin, Xuemei; Kim, Hyun-Yi; Yun, Ji-Hye; Lee, Weontae; Choi, Kang-Yell; No, Kyoung Tai

2018-04-01

The Wnt/β-catenin signaling pathway plays a significant role in the control of osteoblastogenesis and bone formation. CXXC finger protein 5 (CXXC5) has been recently identified as a negative feedback regulator of osteoblast differentiation through a specific interaction with Dishevelled (Dvl) protein. It was reported that targeting the Dvl-CXXC5 interaction could be a novel anabolic therapeutic target for osteoporosis. In this study, complex structure of Dvl PDZ domain and CXXC5 peptide was simulated with molecular dynamics (MD). Based on the structural analysis of binding modes of MD-simulated Dvl PDZ domain with CXXC5 peptide and crystal Dvl PDZ domain with synthetic peptide-ligands, we generated two different pharmacophore models and applied pharmacophore-based virtual screening to discover potent inhibitors of the Dvl-CXXC5 interaction for the anabolic therapy of osteoporosis. Analysis of 16 compounds selected by means of a virtual screening protocol yielded four compounds that effectively disrupted the Dvl-CXXC5 interaction in the fluorescence polarization assay. Potential compounds were validated by fluorescence spectroscopy and nuclear magnetic resonance. We successfully identified a highly potent inhibitor, BMD4722, which directly binds to the Dvl PDZ domain and disrupts the Dvl-CXXC5 interaction. Overall, CXXC5-Dvl PDZ domain complex based pharmacophore combined with various traditional and simple computational methods is a promising approach for the development of modulators targeting the Dvl-CXXC5 interaction, and the potent inhibitor BMD4722 could serve as a starting point to discover or design more potent and specific the Dvl-CXXC5 interaction disruptors.

Architecture of the 99 bp DNA-six-protein regulatory complex of the lambda att site.

PubMed

Sun, Xingmin; Mierke, Dale F; Biswas, Tapan; Lee, Sang Yeol; Landy, Arthur; Radman-Livaja, Marta

2006-11-17

The highly directional and tightly regulated recombination reaction used to site-specifically excise the bacteriophage lambda chromosome out of its E. coli host chromosome requires the binding of six sequence-specific proteins to a 99 bp segment of the phage att site. To gain structural insights into this recombination pathway, we measured 27 FRET distances between eight points on the 99 bp regulatory DNA bound with all six proteins. Triangulation of these distances using a metric matrix distance-geometry algorithm provided coordinates for these eight points. The resulting path for the protein-bound regulatory DNA, which fits well with the genetics, biochemistry, and X-ray crystal structures describing the individual proteins and their interactions with DNA, provides a new structural perspective into the molecular mechanism and regulation of the recombination reaction and illustrates a design by which different families of higher-order complexes can be assembled from different numbers and combinations of the same few proteins.

Optical Ptychographic Microscope for Quantitative Bio-Mechanical Imaging

NASA Astrophysics Data System (ADS)

Anthony, Nicholas; Cadenazzi, Guido; Nugent, Keith; Abbey, Brian

The role that mechanical forces play in biological processes such as cell movement and death is becoming of significant interest to further develop our understanding of the inner workings of cells. The most common method used to obtain stress information is photoelasticity which maps a samples birefringence, or its direction dependent refractive indices, using polarized light. However this method only provides qualitative data and for stress information to be useful quantitative data is required. Ptychography is a method for quantitatively determining the phase of a samples complex transmission function. The technique relies upon the collection of multiple overlapping coherent diffraction patterns from laterally displaced points on the sample. The overlap of measurement points provides complementary information that significantly aids in the reconstruction of the complex wavefield exiting the sample and allows for quantitative imaging of weakly interacting specimens. Here we describe recent advances at La Trobe University Melbourne on achieving quantitative birefringence mapping using polarized light ptychography with applications in cell mechanics. Australian Synchrotron, ARC Centre of Excellence for Advanced Molecular Imaging.

A hybrid BCI for enhanced control of a telepresence robot.

PubMed

Carlson, Tom; Tonin, Luca; Perdikis, Serafeim; Leeb, Robert; del R Millán, José

2013-01-01

Motor-disabled end users have successfully driven a telepresence robot in a complex environment using a Brain-Computer Interface (BCI). However, to facilitate the interaction aspect that underpins the notion of telepresence, users must be able to voluntarily and reliably stop the robot at any moment, not just drive from point to point. In this work, we propose to exploit the user's residual muscular activity to provide a fast and reliable control channel, which can start/stop the telepresence robot at any moment. Our preliminary results show that not only does this hybrid approach increase the accuracy, but it also helps to reduce the workload and was the preferred control paradigm of all the participants.

[Autism in children. Speech, behavior and motor activity point to diagnosis].

PubMed

Neumärker, K J

2001-02-01

Austistic disorders characteristically involve specific impairments of social skills, of the language and of stereotyped body movements. L Kanner and H. Asperger were the first to describe these psychopathologic features, which still form the core of the diagnostic criteria of contemporary psychiatric classification systems, ICD-10 and DSM-IV, in the category pervasive developmental disorders. Useful diagnostic tools have been developed to establish the clinical diagnosis. The results of research point to a predominantly genetic pathogenesis involving a complex interaction of multiple genes. While no causal treatments are available for these heterogenic disorders, there are many therapeutic concepts. Although some treatments may achieve significant improvements, autistic disorders usually mean a lifelong individual impairment.

Binding of Alkali Metal Ions with 1,3,5-Tri(phenyl)benzene and 1,3,5-Tri(naphthyl)benzene: The Effect of Phenyl and Naphthyl Ring Substitution on Cation-π Interactions Revealed by DFT Study.

PubMed

Mirchi, Ali; Sizochenko, Natalia; Dinadayalane, Tandabany; Leszczynski, Jerzy

2017-11-22

The effect of substitution of phenyl and naphthyl rings to benzene was examined to elucidate the cation-π interactions involving alkali metal ions with 1,3,5-tri(phenyl)benzene (TPB) and 1,3,5-tri(naphthyl)benzene (TNB). Benzene, TPB, and four TNB isomers (with ααα, ααβ, αββ, and βββ types of fusion) and their complexes with Li + , Na + , K + , Rb + , and Cs + were optimized using DFT approach with B3LYP and M06-2X functionals in conjunction with the def2-QZVP basis set. Higher relative stability of β,β,β-TNB over α,α,α-TNB can be attributed to peri repulsion, which is defined as the nonbonding repulsive interaction between substituents in the 1- and the 8-positions on the naphthalene core. Binding energies, distances between ring centroid and the metal ions, and the distance to metal ions from the center of other six-membered rings were compared for all complexes. Our computational study reveals that the binding affinity of alkali metal cations increases significantly with the 1,3,5-trisubstitution of phenyl and naphthyl rings to benzene. The detailed computational analyses of geometries, partial charges, binding energies, and ligand organization energies reveal the possibility of favorable C-H···M + interactions when a α-naphthyl group exists in complexes of TNB structures. Like benzene-alkali metal ion complexes, the binding affinity of metal ions follows the order: Li + > Na + > K + > Rb + > Cs + for any considered 1,3,5-trisubstituted benzene systems. In case of TNB, we found that the strength of interactions increases as the fusion point changes from α to β position of naphthalene.

Noether charge, black hole volume, and complexity

NASA Astrophysics Data System (ADS)

Couch, Josiah; Fischler, Willy; Nguyen, Phuc H.

2017-03-01

In this paper, we study the physical significance of the thermodynamic volumes of AdS black holes using the Noether charge formalism of Iyer and Wald. After applying this formalism to study the extended thermodynamics of a few examples, we discuss how the extended thermodynamics interacts with the recent complexity = action proposal of Brown et al. (CA-duality). We, in particular, discover that their proposal for the late time rate of change of complexity has a nice decomposition in terms of thermodynamic quantities reminiscent of the Smarr relation. This decomposition strongly suggests a geometric, and via CA-duality holographic, interpretation for the thermodynamic volume of an AdS black hole. We go on to discuss the role of thermodynamics in complexity = action for a number of black hole solutions, and then point out the possibility of an alternate proposal, which we dub "complexity = volume 2.0". In this alternate proposal the complexity would be thought of as the spacetime volume of the Wheeler-DeWitt patch. Finally, we provide evidence that, in certain cases, our proposal for complexity is consistent with the Lloyd bound whereas CA-duality is not.

Interaction of Phase Singularities on Spiral Wave Tail: Reconsideration of Capturing the Excitable Gap.

PubMed

Tomii, Naoki; Yamazaki, Masatoshi; Arafune, Tatsuhiko; Kamiya, Kaichiro; Nakazawa, Kazuo; Honjo, Haruo; Shibata, Nitaro; Sakuma, Ichiro

2018-03-09

The action mechanism of stimulation toward spiral waves (SWs) owing to the complex excitation patterns that occur just after point stimulation has not yet been experimentally clarified. This study sought to test our hypothesis that the effect of capturing excitable gap of SW by stimulation can also be explained as the interaction of original phase singularity (PS) and PSs induced by the stimulation on the wave tail (WT) of the original SW. Phase variance analysis was used to quantitatively analyze the post-shock PS trajectories. In a two-dimensional subepicardial layer of Langendorff-perfused rabbit hearts, optical mapping was utilized to record the excitation pattern during stimulation. After SW was induced by S1-S2 shock, single biphasic point stimulation S3 was applied. In 70 of the S1-S2-S3 stimulation episodes applied on six hearts, the original PS was clearly observed just before the S3 point stimulation in 37 episodes. Pairwise PSs were newly induced by the S3 in 20 episodes. The original PS collided with the newly-induced PSs in 16 episodes; otherwise, they did not interact with the original PS. SW shift occurred most efficiently when the S3 shock was applied at the relative refractory period, and PS shifted in the direction of WT. Quantitative tracking of PS clarified that stimulation in desirable conditions induces pairwise PSs on WT and that the collision of PSs causes SW shift along the WT. Results of this study indicate the importance of the interaction of shock-induced excitation with the WT for effective stimulation.

Unconventional Superconductivity in Luttinger Semimetals: Theory of Complex Tensor Order and the Emergence of the Uniaxial Nematic State

NASA Astrophysics Data System (ADS)

Boettcher, Igor; Herbut, Igor F.

2018-02-01

We investigate unconventional superconductivity in three-dimensional electronic systems with the chemical potential close to a quadratic band touching point in the band dispersion. Short-range interactions can lead to d -wave superconductivity, described by a complex tensor order parameter. We elucidate the general structure of the corresponding Ginzburg-Landau free energy and apply these concepts to the case of an isotropic band touching point. For a vanishing chemical potential, the ground state of the system is given by the superconductor analogue of the uniaxial nematic state, which features line nodes in the excitation spectrum of quasiparticles. In contrast to the theory of real tensor order in liquid crystals, however, the ground state is selected here by the sextic terms in the free energy. At a finite chemical potential, the nematic state has an additional instability at weak coupling and low temperatures. In particular, the one-loop coefficients in the free energy indicate that at weak coupling genuinely complex orders, which break time-reversal symmetry, are energetically favored. We relate our analysis to recent measurements in the half-Heusler compound YPtBi and discuss the role of cubic crystal symmetry.

Spin–orbit DFT with Analytic Gradients and Applications to Heavy Element Compounds

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

Zhang, Zhiyong

We have implemented the unrestricted DFT approach with one-electron spin–orbit operators in the massively parallel NWChem program. Also implemented is the analytic gradient in the DFT approach with spin–orbit interactions. The current capabilities include single-point calculations and geometry optimization. Vibrational frequencies can be calculated numerically from the analytically calculated gradients. The implementation is based on the spin–orbit interaction operator derived from the effective core potential approach. The exchange functionals used in the implementation are functionals derived for non-spin–orbit calculations, including GGA as well as hybrid functionals. Spin–orbit Hartree–Fock calculations can also be carried out. We have applied the spin–orbit DFTmore » methods to the Uranyl aqua complexes. We have optimized the structures and calculated the vibrational frequencies of both (UO2 2+)aq and (UO2 +)aq with and without spin–orbit effects. The effects of the spin–orbit interaction on the structures and frequencies of these two complexes are discussed. We also carried out calculations for Th2, and several low-lying electronic states are calculated. Our results indicate that, for open-shell systems, there are significant effects due to the spin–orbit effects and the electronic configurations with and without spin–orbit interactions could change due to the occupation of orbitals of larger spin–orbit interactions.« less

Robustness and Contingent History: From Prisoner's Dilemma to Gaia Theory.

PubMed

Harvey, Inman

2018-01-01

In both social systems and ecosystems there is a need to resolve potential conflicts between the interests of individuals and the collective interest of the community. The collective interests need to survive the turbulent dynamics of social and ecological interactions. To see how different systems with different sets of interactions have different degrees of robustness, we need to look at their different contingent histories. We analyze abstract artificial life models of such systems, and note that some prominent examples rely on explicitly ahistorical frameworks; we point out where analyses that ignore a contingent historical context can be fatally flawed. The mathematical foundations of Gaia theory are presented in a form whose very basic and general assumptions point to wide applicability across complex dynamical systems. This highlights surprising connections between robustness and accumulated contingent happenstance, regardless of whether Darwinian evolution is or is not implicated. Real-life studies highlight the role of history, and artificial life studies should do likewise.

Silicon supported lipid-DNA thin film structures at varying temperature studied by energy dispersive X-ray diffraction and neutron reflectivity.

PubMed

Domenici, F; Castellano, C; Dell'Unto, F; Albinati, A; Congiu, A

2011-11-01

Non-viral gene transfection by means of lipid-based nanosystems, such as solid supported lipid assemblies, is often limited due to their lack of stability and the consequent loss of efficiency. Therefore not only a detailed thermo-lyotropic study of these DNA-lipid complexes is necessary to understand their interaction mechanisms, but it can also be considered as a first step in conceiving and developing new transfection biosystems. The aim of our study is a structural characterization of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC)-dimethyl-dioctadecyl-ammonium bromide (DDAB)-DNA complex at varying temperature using the energy dispersive X-ray diffraction (EDXD) and neutron reflectivity (NR) techniques. We have shown the formation of a novel thermo-lyotropic structure of DOPC/DDAB thin film self-organized in multi-lamellar planes on (100)-oriented silicon support by spin coating, thus enlightening its ability to include DNA strands. Our NR measurements indicate that the DOPC/DDAB/DNA complex forms temperature-dependent structures. At 65°C and relative humidity of 100% DNA fragments are buried between single lamellar leaflets constituting the hydrocarbon core of the lipid bilayers. This finding supports the consistency of the hydrophobic interaction model, which implies that the coupling between lipid tails and hypo-hydrated DNA single strands could be the driving force of DNA-lipid complexation. Upon cooling to 25°C, EDXD analysis points out that full-hydrated DOPC-DDAB-DNA can switch in a different metastable complex supposed to be driven by lipid heads-DNA electrostatic interaction. Thermotropic response analysis also clarifies that DOPC has a pivotal role in promoting the formation of our observed thermophylic silicon supported lipids-DNA assembly. Copyright © 2011 Elsevier B.V. All rights reserved.

Conservation of coevolving protein interfaces bridges prokaryote–eukaryote homologies in the twilight zone

PubMed Central

Rodriguez-Rivas, Juan; Marsili, Simone; Juan, David; Valencia, Alfonso

2016-01-01

Protein–protein interactions are fundamental for the proper functioning of the cell. As a result, protein interaction surfaces are subject to strong evolutionary constraints. Recent developments have shown that residue coevolution provides accurate predictions of heterodimeric protein interfaces from sequence information. So far these approaches have been limited to the analysis of families of prokaryotic complexes for which large multiple sequence alignments of homologous sequences can be compiled. We explore the hypothesis that coevolution points to structurally conserved contacts at protein–protein interfaces, which can be reliably projected to homologous complexes with distantly related sequences. We introduce a domain-centered protocol to study the interplay between residue coevolution and structural conservation of protein–protein interfaces. We show that sequence-based coevolutionary analysis systematically identifies residue contacts at prokaryotic interfaces that are structurally conserved at the interface of their eukaryotic counterparts. In turn, this allows the prediction of conserved contacts at eukaryotic protein–protein interfaces with high confidence using solely mutational patterns extracted from prokaryotic genomes. Even in the context of high divergence in sequence (the twilight zone), where standard homology modeling of protein complexes is unreliable, our approach provides sequence-based accurate information about specific details of protein interactions at the residue level. Selected examples of the application of prokaryotic coevolutionary analysis to the prediction of eukaryotic interfaces further illustrate the potential of this approach. PMID:27965389

Conservation of coevolving protein interfaces bridges prokaryote-eukaryote homologies in the twilight zone.

PubMed

Rodriguez-Rivas, Juan; Marsili, Simone; Juan, David; Valencia, Alfonso

2016-12-27

Protein-protein interactions are fundamental for the proper functioning of the cell. As a result, protein interaction surfaces are subject to strong evolutionary constraints. Recent developments have shown that residue coevolution provides accurate predictions of heterodimeric protein interfaces from sequence information. So far these approaches have been limited to the analysis of families of prokaryotic complexes for which large multiple sequence alignments of homologous sequences can be compiled. We explore the hypothesis that coevolution points to structurally conserved contacts at protein-protein interfaces, which can be reliably projected to homologous complexes with distantly related sequences. We introduce a domain-centered protocol to study the interplay between residue coevolution and structural conservation of protein-protein interfaces. We show that sequence-based coevolutionary analysis systematically identifies residue contacts at prokaryotic interfaces that are structurally conserved at the interface of their eukaryotic counterparts. In turn, this allows the prediction of conserved contacts at eukaryotic protein-protein interfaces with high confidence using solely mutational patterns extracted from prokaryotic genomes. Even in the context of high divergence in sequence (the twilight zone), where standard homology modeling of protein complexes is unreliable, our approach provides sequence-based accurate information about specific details of protein interactions at the residue level. Selected examples of the application of prokaryotic coevolutionary analysis to the prediction of eukaryotic interfaces further illustrate the potential of this approach.

Human Cytomegalovirus Nuclear Capsids Associate with the Core Nuclear Egress Complex and the Viral Protein Kinase pUL97

PubMed Central

Sonntag, Eric; Wagner, Sabrina; Strojan, Hanife; Wangen, Christina; Lenac Rovis, Tihana; Lisnic, Berislav; Jonjic, Stipan; Schlötzer-Schrehardt, Ursula; Marschall, Manfred

2018-01-01

The nuclear phase of herpesvirus replication is regulated through the formation of regulatory multi-component protein complexes. Viral genomic replication is followed by nuclear capsid assembly, DNA encapsidation and nuclear egress. The latter has been studied intensely pointing to the formation of a viral core nuclear egress complex (NEC) that recruits a multimeric assembly of viral and cellular factors for the reorganization of the nuclear envelope. To date, the mechanism of the association of human cytomegalovirus (HCMV) capsids with the NEC, which in turn initiates the specific steps of nuclear capsid budding, remains undefined. Here, we provide electron microscopy-based data demonstrating the association of both nuclear capsids and NEC proteins at nuclear lamina budding sites. Specifically, immunogold labelling of the core NEC constituent pUL53 and NEC-associated viral kinase pUL97 suggested an intranuclear NEC-capsid interaction. Staining patterns with phospho-specific lamin A/C antibodies are compatible with earlier postulates of targeted capsid egress at lamina-depleted areas. Important data were provided by co-immunoprecipitation and in vitro kinase analyses using lysates from HCMV-infected cells, nuclear fractions, or infectious virions. Data strongly suggest that nuclear capsids interact with pUL53 and pUL97. Combined, the findings support a refined concept of HCMV nuclear trafficking and NEC-capsid interaction. PMID:29342872

The interaction between felt touch and tactile consequences of observed actions: an action-based somatosensory congruency paradigm.

PubMed

Deschrijver, Eliane; Wiersema, Jan R; Brass, Marcel

2016-07-01

Action observation leads to a representation of both the motor aspect of an observed action (motor simulation) and its somatosensory consequences (action-based somatosensory simulation) in the observer's brain. In the current electroencephalography-study, we investigated the neuronal interplay of action-based somatosensory simulation and felt touch. We presented index or middle finger tapping movements of a human or a wooden hand, while simultaneously presenting 'tap-like' tactile sensations to either the corresponding or non-corresponding fingertip of the participant. We focused on an early stage of somatosensory processing [P50, N100 and N140 sensory evoked potentials (SEPs)] and on a later stage of higher-order processing (P3-complex). The results revealed an interaction effect of animacy and congruency in the early P50 SEP and an animacy effect in the N100/N140 SEPs. In the P3-complex, we found an interaction effect indicating that the influence of congruency was larger in the human than in the wooden hand. We argue that the P3-complex may reflect higher-order self-other distinction by signaling simulated action-based touch that does not match own tactile information. As such, the action-based somatosensory congruency paradigm might help understand higher-order social processes from a somatosensory point of view. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

The structure of Erb1-Ytm1 complex reveals the functional importance of a high-affinity binding between two β-propellers during the assembly of large ribosomal subunits in eukaryotes

PubMed Central

Wegrecki, Marcin; Rodríguez-Galán, Olga; de la Cruz, Jesús; Bravo, Jeronimo

2015-01-01

Ribosome biogenesis is one of the most essential pathways in eukaryotes although it is still not fully characterized. Given the importance of this process in proliferating cells, it is obvious that understanding the macromolecular details of the interactions that take place between the assembly factors, ribosomal proteins and nascent pre-rRNAs is essentially required for the development of new non-genotoxic treatments for cancer. Herein, we have studied the association between the WD40-repeat domains of Erb1 and Ytm1 proteins. These are essential factors for the biogenesis of 60S ribosomal subunits in eukaryotes that form a heterotrimeric complex together with the also essential Nop7 protein. We provide the crystal structure of a dimer formed by the C-terminal part of Erb1 and Ytm1 from Chaetomium thermophilum at 2.1 Å resolution. Using a multidisciplinary approach we show that the β-propeller domains of these proteins interact in a novel manner that leads to a high-affinity binding. We prove that a point mutation within the interface of the complex impairs the interaction between the two proteins and negatively affects growth and ribosome production in yeast. Our study suggests insights into the association of the Erb1-Ytm1 dimer with pre-ribosomal particles. PMID:26476442

Human Cytomegalovirus Nuclear Capsids Associate with the Core Nuclear Egress Complex and the Viral Protein Kinase pUL97.

PubMed

Milbradt, Jens; Sonntag, Eric; Wagner, Sabrina; Strojan, Hanife; Wangen, Christina; Lenac Rovis, Tihana; Lisnic, Berislav; Jonjic, Stipan; Sticht, Heinrich; Britt, William J; Schlötzer-Schrehardt, Ursula; Marschall, Manfred

2018-01-13

The nuclear phase of herpesvirus replication is regulated through the formation of regulatory multi-component protein complexes. Viral genomic replication is followed by nuclear capsid assembly, DNA encapsidation and nuclear egress. The latter has been studied intensely pointing to the formation of a viral core nuclear egress complex (NEC) that recruits a multimeric assembly of viral and cellular factors for the reorganization of the nuclear envelope. To date, the mechanism of the association of human cytomegalovirus (HCMV) capsids with the NEC, which in turn initiates the specific steps of nuclear capsid budding, remains undefined. Here, we provide electron microscopy-based data demonstrating the association of both nuclear capsids and NEC proteins at nuclear lamina budding sites. Specifically, immunogold labelling of the core NEC constituent pUL53 and NEC-associated viral kinase pUL97 suggested an intranuclear NEC-capsid interaction. Staining patterns with phospho-specific lamin A/C antibodies are compatible with earlier postulates of targeted capsid egress at lamina-depleted areas. Important data were provided by co-immunoprecipitation and in vitro kinase analyses using lysates from HCMV-infected cells, nuclear fractions, or infectious virions. Data strongly suggest that nuclear capsids interact with pUL53 and pUL97. Combined, the findings support a refined concept of HCMV nuclear trafficking and NEC-capsid interaction.

The Model of Complex Structure of Quark

NASA Astrophysics Data System (ADS)

Liu, Rongwu

2017-09-01

In Quantum Chromodynamics, quark is known as a kind of point-like fundamental particle which carries mass, charge, color, and flavor, strong interaction takes place between quarks by means of exchanging intermediate particles-gluons. An important consequence of this theory is that, strong interaction is a kind of short-range force, and it has the features of ``asymptotic freedom'' and ``quark confinement''. In order to reveal the nature of strong interaction, the ``bag'' model of vacuum and the ``string'' model of string theory were proposed in the context of quantum mechanics, but neither of them can provide a clear interaction mechanism. This article formulates a new mechanism by proposing a model of complex structure of quark, it can be outlined as follows: (1) Quark (as well as electron, etc) is a kind of complex structure, it is composed of fundamental particle (fundamental matter mass and electricity) and fundamental volume field (fundamental matter flavor and color) which exists in the form of limited volume; fundamental particle lies in the center of fundamental volume field, forms the ``nucleus'' of quark. (2) As static electric force, the color field force between quarks has classical form, it is proportional to the square of the color quantity carried by each color field, and inversely proportional to the area of cross section of overlapping color fields which is along force direction, it has the properties of overlap, saturation, non-central, and constant. (3) Any volume field undergoes deformation when interacting with other volume field, the deformation force follows Hooke's law. (4) The phenomena of ``asymptotic freedom'' and ``quark confinement'' are the result of color field force and deformation force.

Using an agent-based model to analyze the dynamic communication network of the immune response

PubMed Central

2011-01-01

Background The immune system behaves like a complex, dynamic network with interacting elements including leukocytes, cytokines, and chemokines. While the immune system is broadly distributed, leukocytes must communicate effectively to respond to a pathological challenge. The Basic Immune Simulator 2010 contains agents representing leukocytes and tissue cells, signals representing cytokines, chemokines, and pathogens, and virtual spaces representing organ tissue, lymphoid tissue, and blood. Agents interact dynamically in the compartments in response to infection of the virtual tissue. Agent behavior is imposed by logical rules derived from the scientific literature. The model captured the agent-to-agent contact history, and from this the network topology and the interactions resulting in successful versus failed viral clearance were identified. This model served to integrate existing knowledge and allowed us to examine the immune response from a novel perspective directed at exploiting complex dynamics, ultimately for the design of therapeutic interventions. Results Analyzing the evolution of agent-agent interactions at incremental time points from identical initial conditions revealed novel features of immune communication associated with successful and failed outcomes. There were fewer contacts between agents for simulations ending in viral elimination (win) versus persistent infection (loss), due to the removal of infected agents. However, early cellular interactions preceded successful clearance of infection. Specifically, more Dendritic Agent interactions with TCell and BCell Agents, and more BCell Agent interactions with TCell Agents early in the simulation were associated with the immune win outcome. The Dendritic Agents greatly influenced the outcome, confirming them as hub agents of the immune network. In addition, unexpectedly high frequencies of Dendritic Agent-self interactions occurred in the lymphoid compartment late in the loss outcomes. Conclusions An agent-based model capturing several key aspects of complex system dynamics was used to study the emergent properties of the immune response to viral infection. Specific patterns of interactions between leukocyte agents occurring early in the response significantly improved outcome. More interactions at later stages correlated with persistent inflammation and infection. These simulation experiments highlight the importance of commonly overlooked aspects of the immune response and provide insight into these processes at a resolution level exceeding the capabilities of current laboratory technologies. PMID:21247471

Exploring the Multi-Layered Affordances of Composing and Performing Interactive Music with Responsive Technologies.

PubMed

Einarsson, Anna; Ziemke, Tom

2017-01-01

The question motivating the work presented here, starting from a view of music as embodied and situated activity, is how can we account for the complexity of interactive music performance situations. These are situations in which human performers interact with responsive technologies, such as sensor-driven technology or sound synthesis affected by analysis of the performed sound signal. This requires investigating in detail the underlying mechanisms, but also providing a more holistic approach that does not lose track of the complex whole constituted by the interactions and relationships of composers, performers, audience, technologies, etc. The concept of affordances has frequently been invoked in musical research, which has seen a " bodily turn " in recent years, similar to the development of the embodied cognition approach in the cognitive sciences. We therefore begin by broadly delineating its usage in the cognitive sciences in general, and in music research in particular. We argue that what is still missing in the discourse on musical affordances is an encompassing theoretical framework incorporating the sociocultural dimensions that are fundamental to the situatedness and embodiment of interactive music performance and composition. We further argue that the cultural affordances framework, proposed by Rietveld and Kiverstein (2014) and recently articulated further by Ramstead et al. (2016) in this journal, although not previously applied to music, constitutes a promising starting point. It captures and elucidates this complex web of relationships in terms of shared landscapes and individual fields of affordances. We illustrate this with examples foremost from the first author's artistic work as composer and performer of interactive music. This sheds new light on musical composition as a process of construction-and embodied mental simulation-of situations, guiding the performers' and audience's attention in shifting fields of affordances. More generally, we believe that the theoretical perspectives and concrete examples discussed in this paper help to elucidate how situations-and with them affordances-are dynamically constructed through the interactions of various mechanisms as people engage in embodied and situated activity.

See-Through Imaging of Laser-Scanned 3d Cultural Heritage Objects Based on Stochastic Rendering of Large-Scale Point Clouds

NASA Astrophysics Data System (ADS)

Tanaka, S.; Hasegawa, K.; Okamoto, N.; Umegaki, R.; Wang, S.; Uemura, M.; Okamoto, A.; Koyamada, K.

2016-06-01

We propose a method for the precise 3D see-through imaging, or transparent visualization, of the large-scale and complex point clouds acquired via the laser scanning of 3D cultural heritage objects. Our method is based on a stochastic algorithm and directly uses the 3D points, which are acquired using a laser scanner, as the rendering primitives. This method achieves the correct depth feel without requiring depth sorting of the rendering primitives along the line of sight. Eliminating this need allows us to avoid long computation times when creating natural and precise 3D see-through views of laser-scanned cultural heritage objects. The opacity of each laser-scanned object is also flexibly controllable. For a laser-scanned point cloud consisting of more than 107 or 108 3D points, the pre-processing requires only a few minutes, and the rendering can be executed at interactive frame rates. Our method enables the creation of cumulative 3D see-through images of time-series laser-scanned data. It also offers the possibility of fused visualization for observing a laser-scanned object behind a transparent high-quality photographic image placed in the 3D scene. We demonstrate the effectiveness of our method by applying it to festival floats of high cultural value. These festival floats have complex outer and inner 3D structures and are suitable for see-through imaging.

Performance analysis of a dual-tree algorithm for computing spatial distance histograms

PubMed Central

Chen, Shaoping; Tu, Yi-Cheng; Xia, Yuni

2011-01-01

Many scientific and engineering fields produce large volume of spatiotemporal data. The storage, retrieval, and analysis of such data impose great challenges to database systems design. Analysis of scientific spatiotemporal data often involves computing functions of all point-to-point interactions. One such analytics, the Spatial Distance Histogram (SDH), is of vital importance to scientific discovery. Recently, algorithms for efficient SDH processing in large-scale scientific databases have been proposed. These algorithms adopt a recursive tree-traversing strategy to process point-to-point distances in the visited tree nodes in batches, thus require less time when compared to the brute-force approach where all pairwise distances have to be computed. Despite the promising experimental results, the complexity of such algorithms has not been thoroughly studied. In this paper, we present an analysis of such algorithms based on a geometric modeling approach. The main technique is to transform the analysis of point counts into a problem of quantifying the area of regions where pairwise distances can be processed in batches by the algorithm. From the analysis, we conclude that the number of pairwise distances that are left to be processed decreases exponentially with more levels of the tree visited. This leads to the proof of a time complexity lower than the quadratic time needed for a brute-force algorithm and builds the foundation for a constant-time approximate algorithm. Our model is also general in that it works for a wide range of point spatial distributions, histogram types, and space-partitioning options in building the tree. PMID:21804753

Brain correlates of recognition of communicative interactions from biological motion in schizophrenia.

PubMed

Okruszek, Ł; Wordecha, M; Jarkiewicz, M; Kossowski, B; Lee, J; Marchewka, A

2017-11-27

Recognition of communicative interactions is a complex social cognitive ability which is associated with a specific neural activity in healthy individuals. However, neural correlates of communicative interaction processing from whole-body motion have not been known in patients with schizophrenia (SCZ). Therefore, the current study aims to examine the neural activity associated with recognition of communicative interactions in SCZ by using displays of the dyadic interactions downgraded to minimalistic point-light presentations. Twenty-six healthy controls (HC) and 25 SCZ were asked to judge whether two agents presented only by point-light displays were communicating or acting independently. Task-related activity and functional connectivity of brain structures were examined with General Linear Model and Generalized Psychophysiological Interaction approach, respectively. HC were significantly more efficient in recognizing each type of action than SCZ. At the neural level, the activity of the right posterior superior temporal sulcus (pSTS) was observed to be higher in HC compared with SCZ for communicative v. individual action processing. Importantly, increased connectivity of the right pSTS with structures associated with mentalizing (left pSTS) and mirroring networks (left frontal areas) was observed in HC, but not in SCZ, during the presentation of social interactions. Under-recruitment of the right pSTS, a structure known to have a pivotal role in social processing, may also be of importance for higher-order social cognitive deficits in SCZ. Furthermore, decreased task-related connectivity of the right pSTS may result in reduced use of additional sources of information (for instance motor resonance signals) during social cognitive processing in schizophrenia.

On the physical origin of blue-shifted hydrogen bonds.

PubMed

Li, Xiaosong; Liu, Lei; Schlegel, H Bernhard

2002-08-14

For blue-shifted hydrogen-bonded systems, the hydrogen stretching frequency increases rather than decreases on complexation. In computations at various levels of theory, the blue-shift in the archetypical system, F(3)C-H.FH, is reproduced at the Hartree-Fock level, indicating that electron correlation is not the primary cause. Calculations also demonstrate that a blue-shift does not require either a carbon center or the absence of a lone pair on the proton donor, because F(3)Si-H.OH(2), F(2)NH.FH, F(2)PH.NH(3), and F(2)PH.OH(2) have substantial blue-shifts. Orbital interactions are shown to lengthen the X-H bond and lower its vibrational frequency, and thus cannot be the source of the blue-shift. In the F(3)CH.FH system, the charge redistribution in F(3)CH can be reproduced very well by replacing the FH with a simple dipole, which suggests that the interactions are predominantly electrostatic. When modeled with a point charge for the proton acceptor, attractive electrostatic interactions elongate the F(3)C-H, while repulsive interactions shorten it. At the equilibrium geometry of a hydrogen-bonded complex, the electrostatic attraction between the dipole moments of the proton donor and proton acceptor must be balanced by the Pauli repulsion between the two fragments. In the absence of orbital interactions that cause bond elongation, this repulsive interaction leads to compression of the X-H bond and a blue-shift in its vibrational frequency.

Stochastic optimization of GeantV code by use of genetic algorithms

DOE PAGES

Amadio, G.; Apostolakis, J.; Bandieramonte, M.; ...

2017-10-01

GeantV is a complex system based on the interaction of different modules needed for detector simulation, which include transport of particles in fields, physics models simulating their interactions with matter and a geometrical modeler library for describing the detector and locating the particles and computing the path length to the current volume boundary. The GeantV project is recasting the classical simulation approach to get maximum benefit from SIMD/MIMD computational architectures and highly massive parallel systems. This involves finding the appropriate balance between several aspects influencing computational performance (floating-point performance, usage of off-chip memory bandwidth, specification of cache hierarchy, etc.) andmore » handling a large number of program parameters that have to be optimized to achieve the best simulation throughput. This optimization task can be treated as a black-box optimization problem, which requires searching the optimum set of parameters using only point-wise function evaluations. Here, the goal of this study is to provide a mechanism for optimizing complex systems (high energy physics particle transport simulations) with the help of genetic algorithms and evolution strategies as tuning procedures for massive parallel simulations. One of the described approaches is based on introducing a specific multivariate analysis operator that could be used in case of resource expensive or time consuming evaluations of fitness functions, in order to speed-up the convergence of the black-box optimization problem.« less

Stochastic optimization of GeantV code by use of genetic algorithms

NASA Astrophysics Data System (ADS)

Amadio, G.; Apostolakis, J.; Bandieramonte, M.; Behera, S. P.; Brun, R.; Canal, P.; Carminati, F.; Cosmo, G.; Duhem, L.; Elvira, D.; Folger, G.; Gheata, A.; Gheata, M.; Goulas, I.; Hariri, F.; Jun, S. Y.; Konstantinov, D.; Kumawat, H.; Ivantchenko, V.; Lima, G.; Nikitina, T.; Novak, M.; Pokorski, W.; Ribon, A.; Seghal, R.; Shadura, O.; Vallecorsa, S.; Wenzel, S.

2017-10-01

GeantV is a complex system based on the interaction of different modules needed for detector simulation, which include transport of particles in fields, physics models simulating their interactions with matter and a geometrical modeler library for describing the detector and locating the particles and computing the path length to the current volume boundary. The GeantV project is recasting the classical simulation approach to get maximum benefit from SIMD/MIMD computational architectures and highly massive parallel systems. This involves finding the appropriate balance between several aspects influencing computational performance (floating-point performance, usage of off-chip memory bandwidth, specification of cache hierarchy, etc.) and handling a large number of program parameters that have to be optimized to achieve the best simulation throughput. This optimization task can be treated as a black-box optimization problem, which requires searching the optimum set of parameters using only point-wise function evaluations. The goal of this study is to provide a mechanism for optimizing complex systems (high energy physics particle transport simulations) with the help of genetic algorithms and evolution strategies as tuning procedures for massive parallel simulations. One of the described approaches is based on introducing a specific multivariate analysis operator that could be used in case of resource expensive or time consuming evaluations of fitness functions, in order to speed-up the convergence of the black-box optimization problem.

Stochastic optimization of GeantV code by use of genetic algorithms

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

Amadio, G.; Apostolakis, J.; Bandieramonte, M.

GeantV is a complex system based on the interaction of different modules needed for detector simulation, which include transport of particles in fields, physics models simulating their interactions with matter and a geometrical modeler library for describing the detector and locating the particles and computing the path length to the current volume boundary. The GeantV project is recasting the classical simulation approach to get maximum benefit from SIMD/MIMD computational architectures and highly massive parallel systems. This involves finding the appropriate balance between several aspects influencing computational performance (floating-point performance, usage of off-chip memory bandwidth, specification of cache hierarchy, etc.) andmore » handling a large number of program parameters that have to be optimized to achieve the best simulation throughput. This optimization task can be treated as a black-box optimization problem, which requires searching the optimum set of parameters using only point-wise function evaluations. Here, the goal of this study is to provide a mechanism for optimizing complex systems (high energy physics particle transport simulations) with the help of genetic algorithms and evolution strategies as tuning procedures for massive parallel simulations. One of the described approaches is based on introducing a specific multivariate analysis operator that could be used in case of resource expensive or time consuming evaluations of fitness functions, in order to speed-up the convergence of the black-box optimization problem.« less

Modeling and Visualizing Flow of Chemical Agents Across Complex Terrain

NASA Technical Reports Server (NTRS)

Kao, David; Kramer, Marc; Chaderjian, Neal

2005-01-01

Release of chemical agents across complex terrain presents a real threat to homeland security. Modeling and visualization tools are being developed that capture flow fluid terrain interaction as well as point dispersal downstream flow paths. These analytic tools when coupled with UAV atmospheric observations provide predictive capabilities to allow for rapid emergency response as well as developing a comprehensive preemptive counter-threat evacuation plan. The visualization tools involve high-end computing and massive parallel processing combined with texture mapping. We demonstrate our approach across a mountainous portion of North California under two contrasting meteorological conditions. Animations depicting flow over this geographical location provide immediate assistance in decision support and crisis management.

Predicting Physical Interactions between Protein Complexes*

PubMed Central

Clancy, Trevor; Rødland, Einar Andreas; Nygard, Ståle; Hovig, Eivind

2013-01-01

Protein complexes enact most biochemical functions in the cell. Dynamic interactions between protein complexes are frequent in many cellular processes. As they are often of a transient nature, they may be difficult to detect using current genome-wide screens. Here, we describe a method to computationally predict physical interactions between protein complexes, applied to both humans and yeast. We integrated manually curated protein complexes and physical protein interaction networks, and we designed a statistical method to identify pairs of protein complexes where the number of protein interactions between a complex pair is due to an actual physical interaction between the complexes. An evaluation against manually curated physical complex-complex interactions in yeast revealed that 50% of these interactions could be predicted in this manner. A community network analysis of the highest scoring pairs revealed a biologically sensible organization of physical complex-complex interactions in the cell. Such analyses of proteomes may serve as a guide to the discovery of novel functional cellular relationships. PMID:23438732

Hierarchical organization of eglin c native state dynamics is shaped by competing direct and water-mediated interactions.

PubMed

Materese, Christopher Kroboth; Goldmon, Christa Charisse; Papoian, Garegin A

2008-08-05

The native state dynamics of the small globular serine protease inhibitor eglin c has been studied in a long 336 ns computer simulation in explicit solvent. We have elucidated the energy landscape explored during the course of the simulation by using Principal Component Analysis. We observe several basins in the energy landscape in which the system lingers for extended periods. Through an iterative process we have generated a tree-like hierarchy of states describing the observed dynamics. We observe a range of divergent contact types including salt bridges, hydrogen bonds, hydrophilic interactions, and hydrophobic interactions, pointing to the frustration between competing interactions. Additionally, we find evidence of competing water-mediated interactions. Divergence in water-mediated interactions may be found to supplement existing direct contacts, but they are also found to be independent of such changes. Water-mediated contacts facilitate interactions between residues of like charge as observed in the simulation. Our results provide insight into the complexity of the dynamic native state of a globular protein and directly probe the residual frustration in the native state.

ISS Local Environment Spectrometers (ISLES)

NASA Technical Reports Server (NTRS)

Krause, Linda Habash; Gilchrist, Brian E.

2014-01-01

In order to study the complex interactions between the space environment surrounding the ISS and the ISS surface materials, we propose to use lowcost, high-TRL plasma sensors on the ISS robotic arm to probe the ISS space environment. During many years of ISS operation, we have been able to condut effective (but not perfect) extravehicular activities (both human and robotic) within the perturbed local ISS space environment. Because of the complexity of the interaction between the ISS and the LEO space environment, there remain important questions, such as differential charging at solar panel junctions (the so-called "triple point" between conductor, dielectric, and space plasma), increased chemical contamination due to ISS surface charging and/or thruster activation, water dumps, etc, and "bootstrap" charging of insulating surfaces. Some compelling questions could synergistically draw upon a common sensor suite, which also leverages previous and current MSFC investments. Specific questions address ISS surface charging, plasma contactor plume expansion in a magnetized drifting plasma, and possible localized contamination effects across the ISS.

Steered Molecular Dynamics for Investigating the Interactions Between Insulin Receptor Tyrosine Kinase (IRK) and Variants of Protein Tyrosine Phosphatase 1B (PTP1B).

PubMed

Nguyen, Hung; Do, Nhat; Phan, Tuyn; Pham, Tri

2018-02-01

The aim of this study is to use steered molecular dynamics to investigate the dissociation process between IRK and PTP1Bs for wild type and five mutants (consisting of p.D181E, p.D181A, p.Q262A, p.D181A-Y46F, and p.D181A-Q262A). The gained results are observed not only the unbinding mechanism of IRK-PTP1B complexes came from pulling force profile, number of hydrogen bonds, and interaction energy between IRK and PTP1Bs but also described PTP1B's point mutations could variably change its binding affinity towards IRK. Additionally, the binding free energy calculated by Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) is also revealed that electrostatic energy and polar solvation energy mainly made up the binding free energy of PTP1B-IRK complexes.

Agent-based model of diffusion of N-acyl homoserine lactones in a multicellular environment of Pseudomonas aeruginosa and Candida albicans.

PubMed

Pérez-Rodríguez, Gael; Dias, Sónia; Pérez-Pérez, Martín; Fdez-Riverola, Florentino; Azevedo, Nuno F; Lourenço, Anália

2018-03-08

Experimental incapacity to track microbe-microbe interactions in structures like biofilms, and the complexity inherent to the mathematical modelling of those interactions, raises the need for feasible, alternative modelling approaches. This work proposes an agent-based representation of the diffusion of N-acyl homoserine lactones (AHL) in a multicellular environment formed by Pseudomonas aeruginosa and Candida albicans. Depending on the spatial location, C. albicans cells were variably exposed to AHLs, an observation that might help explain why phenotypic switching of individual cells in biofilms occurred at different time points. The simulation and algebraic results were similar for simpler scenarios, although some statistical differences could be observed (p < 0.05). The model was also successfully applied to a more complex scenario representing a small multicellular environment containing C. albicans and P. aeruginosa cells encased in a 3-D matrix. Further development of this model may help create a predictive tool to depict biofilm heterogeneity at the single-cell level.

A Survey of Noninteractive Zero Knowledge Proof System and Its Applications

PubMed Central

Wu, Huixin; Wang, Feng

2014-01-01

Zero knowledge proof system which has received extensive attention since it was proposed is an important branch of cryptography and computational complexity theory. Thereinto, noninteractive zero knowledge proof system contains only one message sent by the prover to the verifier. It is widely used in the construction of various types of cryptographic protocols and cryptographic algorithms because of its good privacy, authentication, and lower interactive complexity. This paper reviews and analyzes the basic principles of noninteractive zero knowledge proof system, and summarizes the research progress achieved by noninteractive zero knowledge proof system on the following aspects: the definition and related models of noninteractive zero knowledge proof system, noninteractive zero knowledge proof system of NP problems, noninteractive statistical and perfect zero knowledge, the connection between noninteractive zero knowledge proof system, interactive zero knowledge proof system, and zap, and the specific applications of noninteractive zero knowledge proof system. This paper also points out the future research directions. PMID:24883407

Taking peer victimization research to the next level: complex interactions among genes, teacher attitudes/behaviors, peer ecologies, & classroom characteristics.

PubMed

Espelage, Dorothy L

2015-01-01

This commentary reviews research findings of the five papers in the special entitled "School-related Factors in the Development of Bullying Perpetration and Victimization", which represent critical areas that are often overlooked in the literature. First, one paper points to the complex interaction between a genetic disposition for aggression and classroom norms toward aggression. Second, an intervention paper unpacks the underlying mechanisms of an efficacious school-wide bully prevention program by opening the "black box" and testing for mediators. Third, the remaining studies employ a wide range of rigorous designs to identify how teachers' attitudes, behaviors, and classroom practices play a critical role in the prevalence of victimization and bullying in the classroom. Further, teachers' attitudes and behaviors are shown to be predictive of youth's willingness to intervene to assist a peer who is being victimized. Results are situated in what is known about bullying prevention, and how the findings from these studies could maximize the sensitivity of future prevention efforts.

Isothiazolidinone (IZD) as a phosphoryl mimetic in inhibitors of the Yersinia pestis protein tyrosine phosphatase YopH

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

Kim, Sung-Eun; Bahta, Medhanit; Lountos, George T.

2011-07-01

The first X-ray crystal structure of the Y. pestis protein tyrosine phosphatase YopH in complex with an isothiazolidinone-based lead-fragment compound is reported. Isothiazolidinone (IZD) heterocycles can act as effective components of protein tyrosine phosphatase (PTP) inhibitors by simultaneously replicating the binding interactions of both a phosphoryl group and a highly conserved water molecule, as exemplified by the structures of several PTP1B–inhibitor complexes. In the first unambiguous demonstration of IZD interactions with a PTP other than PTP1B, it is shown by X-ray crystallography that the IZD motif binds within the catalytic site of the Yersinia pestis PTP YopH by similarly displacingmore » a highly conserved water molecule. It is also shown that IZD-based bidentate ligands can inhibit YopH in a nonpromiscuous fashion at low micromolar concentrations. Hence, the IZD moiety may represent a useful starting point for the development of YopH inhibitors.« less

Limit cycles in piecewise-affine gene network models with multiple interaction loops

NASA Astrophysics Data System (ADS)

Farcot, Etienne; Gouzé, Jean-Luc

2010-01-01

In this article, we consider piecewise affine differential equations modelling gene networks. We work with arbitrary decay rates, and under a local hypothesis expressed as an alignment condition of successive focal points. The interaction graph of the system may be rather complex (multiple intricate loops of any sign, multiple thresholds, etc.). Our main result is an alternative theorem showing that if a sequence of region is periodically visited by trajectories, then under our hypotheses, there exists either a unique stable periodic solution, or the origin attracts all trajectories in this sequence of regions. This result extends greatly our previous work on a single negative feedback loop. We give several examples and simulations illustrating different cases.

Direct evidence for tautomerization of the uracil moiety within the Pb2+/uridine-5'-monophosphate complex: a combined tandem mass spectrometry and IRMPD study.

PubMed

Salpin, Jean-Yves; Guillaumont, Sébastien; Ortiz, Daniel; Tortajada, Jeanine; Maître, Philippe

2011-08-15

The structure of the [Pb(UMP)-H](+) (UMP = uridine-5'-monophosphate) complex was studied in the gas phase by combining electrospray ionization (ESI), tandem mass spectrometry, and mid-infrared multiple photon dissociation (IRMPD) spectroscopy. The results obtained show that Pb(2+) ions interact not only with the deprotonated phosphate group but also with a carbonyl group of the nucleobase moiety by folding of the mononucleotide, resulting in macrochelates that are not likely to be present in solution. Comparison between the IRMPD and DFT-computed spectra suggests that the ESI-generated complex likely corresponds to a mixture of several structures, and establishes the enolic tautomers as the most abundant species for the [Pb(UMP)-H](+) ion, while the very weak IRMPD signal observed at ∼1763 cm(-1) points to a minor population of oxo forms. Our data also suggest that losing the nucleobase residue under CID conditions does not necessarily mean a lack of interaction between the metal and the nucleobase moiety, as commonly reported in the literature for large oligonucleotides. © 2011 American Chemical Society

The complex and specific pMHC interactions with diverse HIV-1 TCR clonotypes reveal a structural basis for alterations in CTL function

PubMed Central

Xia, Zhen; Chen, Huabiao; Kang, Seung-gu; Huynh, Tien; Fang, Justin W.; Lamothe, Pedro A.; Walker, Bruce D.; Zhou, Ruhong

2014-01-01

Immune control of viral infections is modulated by diverse T cell receptor (TCR) clonotypes engaging peptide-MHC class I complexes on infected cells, but the relationship between TCR structure and antiviral function is unclear. Here we apply in silico molecular modeling with in vivo mutagenesis studies to investigate TCR-pMHC interactions from multiple CTL clonotypes specific for a well-defined HIV-1 epitope. Our molecular dynamics simulations of viral peptide-HLA-TCR complexes, based on two independent co-crystal structure templates, reveal that effective and ineffective clonotypes bind to the terminal portions of the peptide-MHC through similar salt bridges, but their hydrophobic side-chain packings can be very different, which accounts for the major part of the differences among these clonotypes. Non-specific hydrogen bonding to viral peptide also accommodates greater epitope variants. Furthermore, free energy perturbation calculations for point mutations on the viral peptide KK10 show excellent agreement with in vivo mutagenesis assays, with new predictions confirmed by additional experiments. These findings indicate a direct structural basis for heterogeneous CTL antiviral function. PMID:24522437

Applying graphs and complex networks to football metric interpretation.

PubMed

Arriaza-Ardiles, E; Martín-González, J M; Zuniga, M D; Sánchez-Flores, J; de Saa, Y; García-Manso, J M

2018-02-01

This work presents a methodology for analysing the interactions between players in a football team, from the point of view of graph theory and complex networks. We model the complex network of passing interactions between players of a same team in 32 official matches of the Liga de Fútbol Profesional (Spain), using a passing/reception graph. This methodology allows us to understand the play structure of the team, by analysing the offensive phases of game-play. We utilise two different strategies for characterising the contribution of the players to the team: the clustering coefficient, and centrality metrics (closeness and betweenness). We show the application of this methodology by analyzing the performance of a professional Spanish team according to these metrics and the distribution of passing/reception in the field. Keeping in mind the dynamic nature of collective sports, in the future we will incorporate metrics which allows us to analyse the performance of the team also according to the circumstances of game-play and to different contextual variables such as, the utilisation of the field space, the time, and the ball, according to specific tactical situations. Copyright © 2017 Elsevier B.V. All rights reserved.

Mammalian TRAPPIII Complex positively modulates the recruitment of Sec13/31 onto COPII vesicles

PubMed Central

Zhao, Shan; Li, Chun Man; Luo, Xiao Min; Siu, Gavin Ka Yu; Gan, Wen Jia; Zhang, Lin; Wu, William K. K.; Chan, Hsiao Chang; Yu, Sidney

2017-01-01

The Transport protein particle (TRAPP) complex is a tethering factor for COPII vesicle. Of three forms of TRAPP (TRAPPI, II and III) complexes identified so far, TRAPPIII has been largely considered to play a role in autophagy. While depletion of TRAPPIII specific subunits caused defects in the early secretory pathway and TRAPPIII might interact with components of the COPII vesicle coat, its exact role remains to be determined. In this study, we studied the function of TRAPPIII in early secretory pathway using a TRAPPIII-specific subunit, TRAPPC12, as starting point. We found that TRAPPC12 was localized to the ER exit sites and ERGIC. In cells deleted with TRAPPC12, ERGIC and to a lesser extent, the Golgi became dispersed. ER-to-Golgi transport was also delayed. TRAPPC12, but not TRAPPC8, bound to Sec13/Sec31A tetramer but each Sec protein alone could not interact with TRAPPC12. TRAPPIII positively modulated the assembly of COPII outer layer during COPII vesicle formation. These results identified a novel function of TRAPPIII as a positive modulator of the outer layer of the COPII coat. PMID:28240221

Viewpoints: Interactive Exploration of Large Multivariate Earth and Space Science Data Sets

NASA Astrophysics Data System (ADS)

Levit, C.; Gazis, P. R.

2006-05-01

Analysis and visualization of extremely large and complex data sets may be one of the most significant challenges facing earth and space science investigators in the forthcoming decades. While advances in hardware speed and storage technology have roughly kept up with (indeed, have driven) increases in database size, the same is not of our abilities to manage the complexity of these data. Current missions, instruments, and simulations produce so much data of such high dimensionality that they outstrip the capabilities of traditional visualization and analysis software. This problem can only be expected to get worse as data volumes increase by orders of magnitude in future missions and in ever-larger supercomputer simulations. For large multivariate data (more than 105 samples or records with more than 5 variables per sample) the interactive graphics response of most existing statistical analysis, machine learning, exploratory data analysis, and/or visualization tools such as Torch, MLC++, Matlab, S++/R, and IDL stutters, stalls, or stops working altogether. Fortunately, the graphics processing units (GPUs) built in to all professional desktop and laptop computers currently on the market are capable of transforming, filtering, and rendering hundreds of millions of points per second. We present a prototype open-source cross-platform application which leverages much of the power latent in the GPU to enable smooth interactive exploration and analysis of large high- dimensional data using a variety of classical and recent techniques. The targeted application is the interactive analysis of large, complex, multivariate data sets, with dimensionalities that may surpass 100 and sample sizes that may exceed 106-108.

A quantitative analysis of statistical power identifies obesity end points for improved in vivo preclinical study design.

PubMed

Selimkhanov, J; Thompson, W C; Guo, J; Hall, K D; Musante, C J

2017-08-01

The design of well-powered in vivo preclinical studies is a key element in building the knowledge of disease physiology for the purpose of identifying and effectively testing potential antiobesity drug targets. However, as a result of the complexity of the obese phenotype, there is limited understanding of the variability within and between study animals of macroscopic end points such as food intake and body composition. This, combined with limitations inherent in the measurement of certain end points, presents challenges to study design that can have significant consequences for an antiobesity program. Here, we analyze a large, longitudinal study of mouse food intake and body composition during diet perturbation to quantify the variability and interaction of the key metabolic end points. To demonstrate how conclusions can change as a function of study size, we show that a simulated preclinical study properly powered for one end point may lead to false conclusions based on secondary end points. We then propose the guidelines for end point selection and study size estimation under different conditions to facilitate proper power calculation for a more successful in vivo study design.

Quaternary structure of a G-protein-coupled receptor heterotetramer in complex with Gi and Gs.

PubMed

Navarro, Gemma; Cordomí, Arnau; Zelman-Femiak, Monika; Brugarolas, Marc; Moreno, Estefania; Aguinaga, David; Perez-Benito, Laura; Cortés, Antoni; Casadó, Vicent; Mallol, Josefa; Canela, Enric I; Lluís, Carme; Pardo, Leonardo; García-Sáez, Ana J; McCormick, Peter J; Franco, Rafael

2016-04-05

G-protein-coupled receptors (GPCRs), in the form of monomers or homodimers that bind heterotrimeric G proteins, are fundamental in the transfer of extracellular stimuli to intracellular signaling pathways. Different GPCRs may also interact to form heteromers that are novel signaling units. Despite the exponential growth in the number of solved GPCR crystal structures, the structural properties of heteromers remain unknown. We used single-particle tracking experiments in cells expressing functional adenosine A1-A2A receptors fused to fluorescent proteins to show the loss of Brownian movement of the A1 receptor in the presence of the A2A receptor, and a preponderance of cell surface 2:2 receptor heteromers (dimer of dimers). Using computer modeling, aided by bioluminescence resonance energy transfer assays to monitor receptor homomerization and heteromerization and G-protein coupling, we predict the interacting interfaces and propose a quaternary structure of the GPCR tetramer in complex with two G proteins. The combination of results points to a molecular architecture formed by a rhombus-shaped heterotetramer, which is bound to two different interacting heterotrimeric G proteins (Gi and Gs). These novel results constitute an important advance in understanding the molecular intricacies involved in GPCR function.

The interaction of two spheres in a simple-shear flow of complex fluids

NASA Astrophysics Data System (ADS)

Firouznia, Mohammadhossein; Metzger, Bloen; Ovarlez, Guillaume; Hormozi, Sarah

2017-11-01

We study the interaction of two small freely-moving spheres in a linear flow field of Newtonian, shear thinning and yield stress fluids. We perform a series of experiments over a range of shear rates as well as different shear histories using an original apparatus and with the aid of conventional rheometry, Particle Image Velocimetry and Particle Tracking Velocimetry. Showing that the non-Newtonian nature of the suspending fluid strongly affects the shape of particle trajectories and the irreversibility. An important point is that non-Newtonian effects can be varied and unusual. Depending on the shear rate, nonideal shear thinning and yield stress suspending fluids might show elasticity that needs to be taken into account. The flow field around one particle is studied in different fluids when subjected to shear. Then using these results to explain the two particle interactions in a simple-shear flow we show how particle-particle contact and non-Newtonian behaviors result in relative trajectories with fore-aft asymmetry. Well-resolved velocity and stress fields around the particles are presented here. Finally, we discuss how the relative particle trajectories may affect the microstructure of complex suspensions and consequently the bulk rheology. NSF (Grant No. CBET-1554044-CAREER).

Inhibition of the Membrane Attack Complex by Dengue Virus NS1 through Interaction with Vitronectin and Terminal Complement Proteins.

PubMed

Conde, Jonas Nascimento; da Silva, Emiliana Mandarano; Allonso, Diego; Coelho, Diego Rodrigues; Andrade, Iamara da Silva; de Medeiros, Luciano Neves; Menezes, Joice Lima; Barbosa, Angela Silva; Mohana-Borges, Ronaldo

2016-11-01

Dengue virus (DENV) infects millions of people worldwide and is a major public health problem. DENV nonstructural protein 1 (NS1) is a conserved glycoprotein that associates with membranes and is also secreted into the plasma in DENV-infected patients. The present study describes a novel mechanism by which NS1 inhibits the terminal complement pathway. We first identified the terminal complement regulator vitronectin (VN) as a novel DENV2 NS1 binding partner by using a yeast two-hybrid system. This interaction was further assessed by enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) assay. The NS1-VN complex was also detected in plasmas from DENV-infected patients, suggesting that this interaction occurs during DENV infection. We also demonstrated that the DENV2 NS1 protein, either by itself or by interacting with VN, hinders the formation of the membrane attack complex (MAC) and C9 polymerization. Finally, we showed that DENV2, West Nile virus (WNV), and Zika virus (ZIKV) NS1 proteins produced in mammalian cells inhibited C9 polymerization. Taken together, our results points to a role for NS1 as a terminal pathway inhibitor of the complement system. Dengue is the most important arthropod-borne viral disease nowadays and is caused by dengue virus (DENV). The flavivirus NS1 glycoprotein has been characterized functionally as a complement evasion protein that can attenuate the activation of the classical, lectin, and alternative pathways. The present study describes a novel mechanism by which DENV NS1 inhibits the terminal complement pathway. We identified the terminal complement regulator vitronectin (VN) as a novel DENV NS1 binding partner, and the NS1-VN complex was detected in plasmas from DENV-infected patients, suggesting that this interaction occurs during DENV infection. We also demonstrated that the NS1-VN complex inhibited membrane attack complex (MAC) formation, thus interfering with the complement terminal pathway. Interestingly, NS1 itself also inhibited MAC activity, suggesting a direct role of this protein in the inhibition process. Our findings imply a role for NS1 as a terminal pathway inhibitor of the complement system. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Implementation of a school-based social and emotional learning intervention: understanding diffusion processes within complex systems.

PubMed

Evans, Rhiannon; Murphy, Simon; Scourfield, Jonathan

2015-07-01

Sporadic and inconsistent implementation remains a significant challenge for social and emotional learning (SEL) interventions. This may be partly explained by the dearth of flexible, causative models that capture the multifarious determinants of implementation practices within complex systems. This paper draws upon Rogers (2003) Diffusion of Innovations Theory to explain the adoption, implementation and discontinuance of a SEL intervention. A pragmatic, formative process evaluation was conducted in alignment with phase 1 of the UK Medical Research Council's framework for Developing and Evaluating Complex Interventions. Employing case-study methodology, qualitative data were generated with four socio-economically and academically contrasting secondary schools in Wales implementing the Student Assistance Programme. Semi-structured interviews were conducted with 15 programme stakeholders. Data suggested that variation in implementation activity could be largely attributed to four key intervention reinvention points, which contributed to the transformation of the programme as it interacted with contextual features and individual needs. These reinvention points comprise the following: intervention training, which captures the process through which adopters acquire knowledge about a programme and delivery expertise; intervention assessment, which reflects adopters' evaluation of an intervention in relation to contextual needs; intervention clarification, which comprises the cascading of knowledge through an organisation in order to secure support in delivery; and intervention responsibility, which refers to the process of assigning accountability for sustainable delivery. Taken together, these points identify opportunities to predict and intervene with potential implementation problems. Further research would benefit from exploring additional reinvention activity.

Non-canonical role of the SNARE protein Ykt6 in autophagosome-lysosome fusion

PubMed Central

Takáts, Szabolcs; Glatz, Gábor; Szenci, Győző; Boda, Attila; Horváth, Gábor V.; Hegedűs, Krisztina; Kovács, Attila L.

2018-01-01

The autophagosomal SNARE Syntaxin17 (Syx17) forms a complex with Snap29 and Vamp7/8 to promote autophagosome-lysosome fusion via multiple interactions with the tethering complex HOPS. Here we demonstrate that, unexpectedly, one more SNARE (Ykt6) is also required for autophagosome clearance in Drosophila. We find that loss of Ykt6 leads to large-scale accumulation of autophagosomes that are unable to fuse with lysosomes to form autolysosomes. Of note, loss of Syx5, the partner of Ykt6 in ER-Golgi trafficking does not prevent autolysosome formation, pointing to a more direct role of Ykt6 in fusion. Indeed, Ykt6 localizes to lysosomes and autolysosomes, and forms a SNARE complex with Syx17 and Snap29. Interestingly, Ykt6 can be outcompeted from this SNARE complex by Vamp7, and we demonstrate that overexpression of Vamp7 rescues the fusion defect of ykt6 loss of function cells. Finally, a point mutant form with an RQ amino acid change in the zero ionic layer of Ykt6 protein that is thought to be important for fusion-competent SNARE complex assembly retains normal autophagic activity and restores full viability in mutant animals, unlike palmitoylation or farnesylation site mutant Ykt6 forms. As Ykt6 and Vamp7 are both required for autophagosome-lysosome fusion and are mutually exclusive subunits in a Syx17-Snap29 complex, these data suggest that Vamp7 is directly involved in membrane fusion and Ykt6 acts as a non-conventional, regulatory SNARE in this process. PMID:29694367

Complex systems: physics beyond physics

NASA Astrophysics Data System (ADS)

Holovatch, Yurij; Kenna, Ralph; Thurner, Stefan

2017-03-01

Complex systems are characterised by specific time-dependent interactions among their many constituents. As a consequence they often manifest rich, non-trivial and unexpected behaviour. Examples arise both in the physical and non-physical worlds. The study of complex systems forms a new interdisciplinary research area that cuts across physics, biology, ecology, economics, sociology, and the humanities. In this paper we review the essence of complex systems from a physicists' point of view, and try to clarify what makes them conceptually different from systems that are traditionally studied in physics. Our goal is to demonstrate how the dynamics of such systems may be conceptualised in quantitative and predictive terms by extending notions from statistical physics and how they can often be captured in a framework of co-evolving multiplex network structures. We mention three areas of complex-systems science that are currently studied extensively, the science of cities, dynamics of societies, and the representation of texts as evolutionary objects. We discuss why these areas form complex systems in the above sense. We argue that there exists plenty of new ground for physicists to explore and that methodical and conceptual progress is needed most.

Volumetric data analysis using Morse-Smale complexes

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

Natarajan, V; Pascucci, V

2005-10-13

The 3D Morse-Smale complex is a fundamental topological construct that partitions the domain of a real-valued function into regions having uniform gradient flow behavior. In this paper, we consider the construction and selective presentation of cells of the Morse-Smale complex and their use in the analysis and visualization of scientific datasets. We take advantage of the fact that cells of different dimension often characterize different types of features present in the data. For example, critical points pinpoint changes in topology by showing where components of the level sets are created, destroyed or modified in genus. Edges of the Morse-Smale complexmore » extract filament-like features that are not explicitly modeled in the original data. Interactive selection and rendering of portions of the Morse-Smale complex introduces fundamental data management challenges due to the unstructured nature of the complex even for structured inputs. We describe a data structure that stores the Morse-Smale complex and allows efficient selective traversal of regions of interest. Finally, we illustrate the practical use of this approach by applying it to cryo-electron microscopy data of protein molecules.« less

The role of CH/π interactions in the high affinity binding of streptavidin and biotin.

PubMed

Ozawa, Motoyasu; Ozawa, Tomonaga; Nishio, Motohiro; Ueda, Kazuyoshi

2017-08-01

The streptavidin-biotin complex has an extraordinarily high affinity (Ka: 10 15 mol -1 ) and contains one of the strongest non-covalent interactions known. This strong interaction is widely used in biological tools, including for affinity tags, detection, and immobilization of proteins. Although hydrogen bond networks and hydrophobic interactions have been proposed to explain this high affinity, the reasons for it remain poorly understood. Inspired by the deceased affinity of biotin observed for point mutations of streptavidin at tryptophan residues, we hypothesized that a CH/π interaction may also contribute to the strong interaction between streptavidin and biotin. CH/π interactions were explored and analyzed at the biotin-binding site and at the interface of the subunits by the fragment molecular orbital method (FMO) and extended applications: PIEDA and FMO4. The results show that CH/π interactions are involved in the high affinity for biotin at the binding site of streptavidin. We further suggest that the involvement of CH/π interactions at the subunit interfaces and an extended CH/π network play more critical roles in determining the high affinity, rather than involvement at the binding site. Copyright © 2017 Elsevier Inc. All rights reserved.

Dynamics driving function: new insights from electron transferring flavoproteins and partner complexes.

PubMed

Toogood, Helen S; Leys, David; Scrutton, Nigel S

2007-11-01

Electron transferring flavoproteins (ETFs) are soluble heterodimeric FAD-containing proteins that function primarily as soluble electron carriers between various flavoprotein dehydrogenases. ETF is positioned at a key metabolic branch point, responsible for transferring electrons from up to 10 primary dehydrogenases to the membrane-bound respiratory chain. Clinical mutations of ETF result in the often fatal disease glutaric aciduria type II. Structural and biophysical studies of ETF in complex with partner proteins have shown that ETF partitions the functions of partner binding and electron transfer between (a) a 'recognition loop', which acts as a static anchor at the ETF-partner interface, and (b) a highly mobile redox-active FAD domain. Together, this enables the FAD domain of ETF to sample a range of conformations, some compatible with fast interprotein electron transfer. This 'conformational sampling' enables ETF to recognize structurally distinct partners, whilst also maintaining a degree of specificity. Complex formation triggers mobility of the FAD domain, an 'induced disorder' mechanism contrasting with the more generally accepted models of protein-protein interaction by induced fit mechanisms. We discuss the implications of the highly dynamic nature of ETFs in biological interprotein electron transfer. ETF complexes point to mechanisms of electron transfer in which 'dynamics drive function', a feature that is probably widespread in biology given the modular assembly and flexible nature of biological electron transfer systems.

Coastline complexity: A parameter for functional classification of coastal environments

USGS Publications Warehouse

Bartley, J.D.; Buddemeier, R.W.; Bennett, D.A.

2001-01-01

To understand the role of the world's coastal zone (CZ) in global biogeochemical fluxes (particularly those of carbon, nitrogen, phosphorus, and sediments) we must generalise from a limited number of observations associated with a few well-studied coastal systems to the global scale. Global generalisation must be based on globally available data and on robust techniques for classification and upscaling. These requirements impose severe constraints on the set of variables that can be used to extract information about local CZ functions such as advective and metabolic fluxes, and differences resulting from changes in biotic communities. Coastal complexity (plan-view tortuosity of the coastline) is a potentially useful parameter, since it interacts strongly with both marine and terrestrial forcing functions to determine coastal energy regimes and water residence times, and since 'open' vs. 'sheltered' categories are important components of most coastal habitat classification schemes. This study employs the World Vector Shoreline (WVS) dataset, originally developed at a scale of 1:250 000. Coastline complexity measures are generated using a modification of the Angle Measurement Technique (AMT), in which the basic measurement is the angle between two lines of specified length drawn from a selected point to the closest points of intersection with the coastline. Repetition of these measurements for different lengths at the same point yields a distribution of angles descriptive of the extent and scale of complexity in the vicinity of that point; repetition of the process at different points on the coast provides a basis for comparing both the extent and the characteristic scale of coastline variation along different reaches of the coast. The coast of northwestern Mexico (Baja California and the Gulf of California) was used as a case study for initial development and testing of the method. The characteristic angle distribution plots generated by the AMT analysis were clustered using LOICZVIEW, a high dimensionality clustering routine developed for large-scale coastal classification studies. The results show distinctive differences in coastal environments that have the potential for interpretation in terms of both biotic and hydrogeochemical environments, and that can be related to the resolution limits and uncertainties of the shoreline data used. These objective, quantitative measures of coastal complexity as a function of scale can be further developed and combined with other data sets to provide a key component of functional classification of coastal environments. ?? 2001 Elsevier Science B.V. All rights reserved.

SPACEBAR: Kinematic design by computer graphics

NASA Technical Reports Server (NTRS)

Ricci, R. J.

1975-01-01

The interactive graphics computer program SPACEBAR, conceived to reduce the time and complexity associated with the development of kinematic mechanisms on the design board, was described. This program allows the direct design and analysis of mechanisms right at the terminal screen. All input variables, including linkage geometry, stiffness, and applied loading conditions, can be fed into or changed at the terminal and may be displayed in three dimensions. All mechanism configurations can be cycled through their range of travel and viewed in their various geometric positions. Output data includes geometric positioning in orthogonal coordinates of each node point in the mechanism, velocity and acceleration of the node points, and internal loads and displacements of the node points and linkages. All analysis calculations take at most a few seconds to complete. Output data can be viewed at the scope and also printed at the discretion of the user.

A systematic analysis of the Braitenberg vehicle 2b for point-like stimulus sources.

PubMed

Rañó, Iñaki

2012-09-01

Braitenberg vehicles have been used experimentally for decades in robotics with limited empirical understanding. This paper presents the first mathematical model of the vehicle 2b, displaying so-called aggression behaviour, and analyses the possible trajectories for point-like smooth stimulus sources. This sensory-motor steering control mechanism is used to implement biologically grounded target approach, target-seeking or obstacle-avoidance behaviour. However, the analysis of the resulting model reveals that complex and unexpected trajectories can result even for point-like stimuli. We also prove how the implementation of the controller and the vehicle morphology interact to affect the behaviour of the vehicle. This work provides a better understanding of Braitenberg vehicle 2b, explains experimental results and paves the way for a formally grounded application on robotics as well as for a new way of understanding target seeking in biology.

The Role of Molecular Motors in the Mechanics of Active Gels and the Effects of Inertia, Hydrodynamic Interaction and Compressibility in Passive Microrheology

DTIC Science & Technology

2014-07-01

to use the two-point microrheology technique 88 to measure the complex compressibility of biopolymers and cell components such as F-actin and...loads [23, 115]. Several works have used a continuum-mechanics level of description to model self- organization [64, 2] and rheology [79, 12, 33] of...morphogenesis [94]. Several works have used a continuum-mechanics level of description to model self- organization [64, 2] and rheology [79, 12, 33] of

Mixed cerium-platinum oxides: Electronic structure of [CeO]Pt{sub n} (n = 1, 2) and [CeO{sub 2}]Pt complex anions and neutrals

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

Ray, Manisha; Kafader, Jared O.; Topolski, Josey E.

The electronic structures of several small Ce–Pt oxide complexes were explored using a combination of anion photoelectron (PE) spectroscopy and density functional theory calculations. Pt and Pt{sub 2} both accept electron density from CeO diatomic molecules, in which the cerium atom is in a lower-than-bulk oxidation state (+2 versus bulk +4). Neutral [CeO]Pt and [CeO]Pt{sub 2} complexes are therefore ionic, with electronic structures described qualitatively as [CeO{sup +2}]Pt{sup −2} and [CeO{sup +}]Pt{sub 2}{sup −}, respectively. The associated anions are described qualitatively as [CeO{sup +}]Pt{sup −2} and [CeO{sup +}]Pt{sub 2}{sup −2}, respectively. In both neutrals and anions, the most stable molecularmore » structures determined by calculations feature a distinct CeO moiety, with the positively charged Ce center pointing toward the electron rich Pt or Pt{sub 2} moiety. Spectral simulations based on calculated spectroscopic parameters are in fair agreement with the spectra, validating the computationally determined structures. In contrast, when Pt is coupled with CeO{sub 2}, which has no Ce-localized electrons that can readily be donated to Pt, the anion is described as [CeO{sub 2}]Pt{sup −}. The molecular structure predicted computationally suggests that it is governed by charge-dipole interactions. The neutral [CeO{sub 2}]Pt complex lacks charge-dipole stabilizing interactions, and is predicted to be structurally very different from the anion, featuring a single Pt–O–Ce bridge bond. The PE spectra of several of the complexes exhibit evidence of photodissociation with Pt{sup −} daughter ion formation. The electronic structures of these complexes are related to local interactions in Pt-ceria catalyst-support systems.« less

The human Ino80 binds to microtubule via the E-hook of tubulin: Implications for the role in spindle assembly

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

Park, Eun-Jung; Hur, Shin-Kyoung; Lee, Han-Sae

2011-12-16

Highlights: Black-Right-Pointing-Pointer The N-terminal domain of hIno80 is important for binding to the spindle. Black-Right-Pointing-Pointer The hIno80 N-terminal domain binds to tubulin and microtubule in vitro. Black-Right-Pointing-Pointer The E-hook of tubulin is critical for hIno80 binding to tubulin and microtubule. Black-Right-Pointing-Pointer Tip49a does not bind to microtubule and dispensable for spindle formation. -- Abstract: The human INO80 chromatin remodeling complex, comprising the Ino80 ATPase (hIno80) and the associated proteins such as Tip49a, has been implicated in a variety of nuclear processes other than transcription. We previously have found that hIno80 interacts with tubulin and co-localizes with the mitotic spindle andmore » is required for spindle formation. To better understand the role of hIno80 in spindle formation, we further investigated the interaction between hIno80 and microtubule. Here, we show that the N-terminal domain, dispensable for the nucleosome remodeling activity, is important for hIno80 to interact with tubulin and co-localize with the spindle. The hIno80 N-terminal domain binds to monomeric tubulin and polymerized microtubule in vitro, and the E-hook of tubulin, involved in the polymerization of microtubule, is critical for this binding. Tip49a, which has been reported to associate with the spindle, does not bind to microtubule in vitro and dispensable for spindle formation in vivo. These results suggest that hIno80 can play a direct role in the spindle assembly independent of its chromatin remodeling activity.« less

Effect of Promoting High-Quality Staff Interactions on Fall Prevention in Nursing Homes: A Cluster-Randomized Trial.

PubMed

Colón-Emeric, Cathleen S; Corazzini, Kirsten; McConnell, Eleanor S; Pan, Wei; Toles, Mark; Hall, Rasheeda; Cary, Michael P; Batchelor-Murphy, Melissa; Yap, Tracey; Anderson, Amber L; Burd, Andrew; Amarasekara, Sathya; Anderson, Ruth A

2017-11-01

New approaches are needed to enhance implementation of complex interventions for geriatric syndromes such as falls. To test whether a complexity science-based staff training intervention (CONNECT) promoting high-quality staff interactions improves the impact of an evidence-based falls quality improvement program (FALLS). Cluster-randomized trial in 24 nursing homes receiving either CONNECT followed by FALLS (intervention), or FALLS alone (control). Nursing home staff in all positions were asked to complete surveys at baseline, 3, 6, and 9 months. Medical records of residents with at least 1 fall in the 6-month pre- and postintervention windows (n = 1794) were abstracted for fall risk reduction measures, falls, and injurious falls. CONNECT taught staff to improve their connections with coworkers, increase information flow, and use cognitive diversity in problem solving. Intervention components included 2 classroom sessions, relationship mapping, and self-monitoring. FALLS provided instruction in the Agency for Healthcare Research and Quality's Falls Management Program. Primary outcomes were (1) mean number of fall risk reduction activities documented within 30 days of falls and (2) median fall rates among residents with at least 1 fall during the study period. In addition, validated scales measured staff communication quality, frequency, timeliness, and safety climate. Surveys were completed by 1545 staff members, representing 734 (37%) and 811 (44%) of eligible staff in intervention and control facilities, respectively; 511 (33%) respondents were hands-on care workers. Neither the CONNECT nor the FALLS-only facilities improved the mean count of fall risk reduction activities following FALLS (3.3 [1.6] vs 3.2 [1.5] of 10); furthermore, adjusted median recurrent fall rates did not differ between the groups (4.06 [interquartile range {IQR}, 2.03-8.11] vs 4.06 [IQR, 2.04-8.11] falls/resident/y). A modest improvement in staff communication measures was observed overall (mean, 0.03 [SE, 0.01] points on a 5-point scale; P = .03) and for communication timeliness (mean, 0.8 [SE, 0.03] points on a 5-point scale; P = .02). There was wide variation across facilities in intervention penetration. An intervention targeting gaps in staff communication and coordination did not improve the impact of a falls quality improvement program. New approaches to implementing evidence-based care for complex conditions in the nursing home are urgently needed. clinicaltrials.gov Identifier: NCT00636675.

Combined point and distributed techniques for multidimensional estimation of spatial groundwater-stream water exchange in a heterogeneous sand bed-stream.

NASA Astrophysics Data System (ADS)

Gaona Garcia, J.; Lewandowski, J.; Bellin, A.

2017-12-01

Groundwater-stream water interactions in rivers determine water balances, but also chemical and biological processes in the streambed at different spatial and temporal scales. Due to the difficult identification and quantification of gaining, neutral and losing conditions, it is necessary to combine techniques with complementary capabilities and scale ranges. We applied this concept to a study site at the River Schlaube, East Brandenburg-Germany, a sand bed stream with intense sediment heterogeneity and complex environmental conditions. In our approach, point techniques such as temperature profiles of the streambed together with vertical hydraulic gradients provide data for the estimation of fluxes between groundwater and surface water with the numerical model 1DTempPro. On behalf of distributed techniques, fiber optic distributed temperature sensing identifies the spatial patterns of neutral, down- and up-welling areas by analysis of the changes in the thermal patterns at the streambed interface under certain flow. The study finally links point and surface temperatures to provide a method for upscaling of fluxes. Point techniques provide point flux estimates with essential depth detail to infer streambed structures while the results hardly represent the spatial distribution of fluxes caused by the heterogeneity of streambed properties. Fiber optics proved capable of providing spatial thermal patterns with enough resolution to observe distinct hyporheic thermal footprints at multiple scales. The relation of thermal footprint patterns and temporal behavior with flux results from point techniques enabled the use of methods for spatial flux estimates. The lack of detailed information of the physical driver's spatial distribution restricts the spatial flux estimation to the application of the T-proxy method, whose highly uncertain results mainly provide coarse spatial flux estimates. The study concludes that the upscaling of groundwater-stream water interactions using thermal measurements with combined point and distributed techniques requires the integration of physical drivers because of the heterogeneity of the flux patterns. Combined experimental and modeling approaches may help to obtain more reliable understanding of groundwater-surface water interactions at multiple scales.

Jet Interactions in a Feedback-Free Fluidic Oscillator in the Transition Region

NASA Astrophysics Data System (ADS)

Tomac, Mehmet; Gregory, James

2013-11-01

The details of the jet interactions and oscillation mechanism of a feedback-free type fluidic oscillator are studied in this work. Flow rate-frequency measurements indicate the existence of three distinct operating regimes: low flow rate, transition, and high flow rate regions. This study presents results from the transition regime, extracted by using refractive index-matched particle image velocimetry (PIV). A newly-developed sensor configuration for frequency measurements in the refractive index-matched fluid and a phase-averaging method that minimizes jitter will be discussed. Experimental results indicate that the interactions of the two jets create three main vortices in the mixing chamber. One vortex vanishes and forms depending on the oscillation phase and plays a key role in the oscillation mechanism. The other two vortices sustain their existence throughout the oscillation cycle; however, both continuously change their size and strength. The resulting complex flow field with self-sustained oscillations is a result of the combination of many interesting phenomena such as jet interactions and bifurcations, viscous effects, vortex-shear layer interactions, vortex-wall interactions, instabilities, and saddle point creations.

Staufen2 isoforms localize to the somatodendritic domain of neurons and interact with different organelles.

PubMed

Duchaîne, Thomas F; Hemraj, Indradeo; Furic, Luc; Deitinghoff, Anke; Kiebler, Michael A; DesGroseillers, Luc

2002-08-15

Mammalian Staufen2 (Stau2) is involved in mRNA transport in neurons. Here, we report that Stau2 is a double-stranded RNA-binding protein that is mainly expressed in the brain. We show that Stau2 is found in the somatodendritic compartment of neurons. In dendrites, Stau2 is aligned on individual tracts and colocalizes with microtubules. Stau2 is expressed as at least three splice isoforms, which can be observed in several subcellular complexes. Although a 62 kDa isoform (Stau2(62)) fractionates in ribosome-free fractions of light density, Stau2(59) and Stau2(52) are found in high-density complexes. These complexes are resistant to EDTA and to non-ionic detergent. For the first time, we also provide evidence for an interaction of some Stau2 isoforms with ribosomes, thus pointing to an interesting new role for Stau2 in translation. EDTA treatment, which dissociates ribosome subunits, does not release Stau2 from the subunits, suggesting that Stau2-ribosome associations are not mediated mainly by mRNA intermediates. Although Stau2 has many features in common with its paralogue Stau1, it does not colocalize with Stau1-containing particles, indicating that these proteins are components of different complexes in dendrites. Our findings suggest that members of the Staufen family share evolutionarily conserved properties and highlight the complexity of Staufen-mediated RNA transport in neurons.

Delineation of the calcineurin-interacting region of cyclophilin B.

PubMed

Carpentier, M; Allain, F; Haendler, B; Slomianny, M C; Spik, G

2000-12-01

The immunosuppressant drug cyclosporin A (CsA) inhibits T-cell function by blocking the phosphatase activity of calcineurin. This effect is mediated by formation of a complex between the drug and cyclophilin (CyP), which creates a composite surface able to make high-affinity contacts with calcineurin. In vitro, the CyPB/CsA complex is more effective in inhibiting calcineurin than the CyPA/CsA and CyPC/CsA complexes, pointing to fine structural differences in the calcineurin-binding region. To delineate the calcineurin-binding region of CyPB, we mutated several amino acids, located in two loops corresponding to CyPA regions known to be involved, as follows: R76A, G77H, D155R, and D158R. Compared to wild-type CyPB, the G77H, D155R, and D158R mutants had intact isomerase and CsA-binding activities, indicating that no major conformational changes had taken place. When complexed to CsA, they all displayed only reduced affinity for calcineurin and much decreased inhibition of calcineurin phosphatase activity. These results strongly suggest that the three amino acids G77, D155, and D158 are directly involved in the interaction of CyPB/CsA with calcineurin, in agreement with their exposed position. The G77, D155, and D158 residues are not maintained in CyPA and might therefore account for the higher affinity of the CyPB/CsA complex for calcineurin.

Arctic systems in the Quaternary: ecological collision, faunal mosaics and the consequences of a wobbling climate.

PubMed

Hoberg, E P; Cook, J A; Agosta, S J; Boeger, W; Galbreath, K E; Laaksonen, S; Kutz, S J; Brooks, D R

2017-07-01

Climate oscillations and episodic processes interact with evolution, ecology and biogeography to determine the structure and complex mosaic that is the biosphere. Parasites and parasite-host assemblages are key components in a general explanatory paradigm for global biodiversity. We explore faunal assembly in the context of Quaternary time frames of the past 2.6 million years, a period dominated by episodic shifts in climate. Climate drivers cross a continuum from geological to contemporary timescales and serve to determine the structure and distribution of complex biotas. Cycles within cycles are apparent, with drivers that are layered, multifactorial and complex. These cycles influence the dynamics and duration of shifts in environmental structure on varying temporal and spatial scales. An understanding of the dynamics of high-latitude systems, the history of the Beringian nexus (the intermittent land connection linking Eurasia and North America) and downstream patterns of diversity depend on teasing apart the complexity of biotic assembly and persistence. Although climate oscillations have dominated the Quaternary, contemporary dynamics are driven by tipping points and shifting balances emerging from anthropogenic forces that are disrupting ecological structure. Climate change driven by anthropogenic forcing has supplanted a history of episodic variation and is eliminating ecological barriers and constraints on development and distribution for pathogen transmission. A framework to explore interactions of episodic processes on faunal structure and assembly is the Stockholm Paradigm, which appropriately shifts the focus from cospeciation to complexity and contingency in explanations of diversity.

Multiple Hydrogen Bond Tethers for Grazing Formic Acid in Its Complexes with Phenylacetylene.

PubMed

Karir, Ginny; Kumar, Gaurav; Kar, Bishnu Prasad; Viswanathan, K S

2018-03-01

Complexes of phenylacetylene (PhAc) and formic acid (FA) present an interesting picture, where the two submolecules are tethered, sometimes multiply, by hydrogen bonds. The multiple tentacles adopted by PhAc-FA complexes stem from the fact that both submolecules can, in the same complex, serve as proton acceptors and/or proton donors. The acetylenic and phenyl π systems of PhAc can serve as proton acceptors, while the ≡C-H or -C-H of the phenyl ring can act as a proton donor. Likewise, FA also is amphiprotic. Hence, more than 10 hydrogen-bonded structures, involving O-H···π, C-H···π, and C-H···O contacts, were indicated by our computations, some with multiple tentacles. Interestingly, despite the multiple contacts in the complexes, the barrier between some of the structures is small, and hence, FA grazes around PhAc, even while being tethered to it, with hydrogen bonds. We used matrix isolation infrared spectroscopy to experimentally study the PhAc-FA complexes, with which we located global and a few local minima, involving primarily an O-H···π interaction. Experiments were corroborated by ab initio computations, which were performed using MP2 and M06-2X methods, with 6-311++G (d,p) and aug-cc-pVDZ basis sets. Single-point energy calculations were also done at MP2/CBS and CCSD(T)/CBS levels. The nature, strength, and origin of these noncovalent interactions were studied using AIM, NBO, and LMO-EDA analysis.

Single Molecule Measurements of Interaction Free Energies Between the Proteins Within Binary and Ternary SNARE Complexes

PubMed Central

Liu, W.; Montana, Vedrana; Parpura, Vladimir; Mohideen, U.

2010-01-01

We use an Atomic Force Microscope based single molecule measurements to evaluate the activation free energy in the interaction of SNARE proteins syntaxin 1A, SNAP25B and synaptobrevin 2 which regulate intracellular fusion of vesicles with target membranes. The dissociation rate of the binary syntaxin-synaptobrevin and the ternary syntaxin-SNAP25B-synaptobrevin complex was measured from the rupture force distribution as a function of the rate of applied force. The temperature dependence of the spontaneous dissociation rate was used to obtain the activation energy to the transition state of 19.8 ± 3.5 kcal/mol = 33 ± 6 kBT and 25.7 ± 3.0 kcal/mol = 43 ± 5 kBT for the binary and ternary complex, respectively. They are consistent with those measured previously for the ternary complex in lipid membranes and are of order expected for bilayer fusion and pore formation. The ΔG was 12.4–16.6 kcal/mol = 21–28 kBT and 13.8–18.0 kcal/mol = 23–30 kBT for the binary and ternary complex, respectively. The ternary complex was more stable by 1.4 kcal/mol = 2.3 kBT, consistent with the spontaneous dissociation rates. The higher adhesion energies and smaller molecular extensions measured with SNAP25B point to its possible unique and important physiological role in tethering/docking the vesicle in closer proximity to the plasma membrane and increasing the probability for fusion completion. PMID:20107522

Enhanced robustness of evolving open systems by the bidirectionality of interactions between elements.

PubMed

Ogushi, Fumiko; Kertész, János; Kaski, Kimmo; Shimada, Takashi

2017-08-01

Living organisms, ecosystems, and social systems are examples of complex systems in which robustness against inclusion of new elements is an essential feature. A recently proposed simple model has revealed a general mechanism by which such systems can become robust against inclusion of elements with totally random interactions when the elements have a moderate number of links. The interaction is, however, in many systems often intrinsically bidirectional like for mutual symbiosis and competition in ecology. This study reports the strong reinforcement effect of the bidirectionality of the interactions on the robustness of evolving systems. We show that the system with purely bidirectional interactions can grow with twofold average degree, in comparison with the purely unidirectional system. This drastic shift of the transition point comes from the reinforcement of each node, not from a change in structure of the emergent system. For systems with partially bidirectional interactions we find that the regime of the growing phase gets expanded. In the dense interaction regime, there exists an optimum proportion of bidirectional interactions for the growth rate at around 1/3. In the sparsely connected systems, small but finite fraction of bidirectional links can change the system's behaviour from non-growing to growing.

Electrostatic interactions lead to the formation of asymmetric collagen-phosphophoryn aggregates.

PubMed

Dahl, Thomas; Veis, Arthur

2003-01-01

In bone and dentin the formation and mineralization of the extra cellular matrix structure is a complex process highly dependent on intermolecular interactions. In dentin, the phosphophoryns (PP) and type I collagen (COL1) are the major constituents implicated in mineralization. Thus, as a first step in understanding the tissue organization, we have initiated a study of their interaction as a function of pH, ionic strength, and relative concentrations or mixing ratios. Complex formation has been analyzed by dynamic light scattering to detect aggregate formation and by rotary shadowing electron microscopy (EM) to determine aggregate shape. The EM data showed that at the pH values studied, the PP-COL1 interaction leads to the formation of large fibrillar aggregates in which the PP are present along the fibril surfaces. The quantitative phase distribution data showed a 1/1 molar equivalence at the maximum aggregation point, not at electrostatic PP-COL1 equivalence. As the ionic strength was raised, the PP-COL1 aggregates became smaller but the binding and asymmetric fibrillar aggregation persisted. In EM, the PP appear as dense spheres. Along the surfaces of the collagen aggregates, the PP are larger and more open or extended, suggesting that COL1-bound PP may undergo a conformational change, opening up so that a single PP molecule might interact with and electrostatically link several COL1 molecules. This might have important implications for dentin structure, stability, and mineralization.

Modeling dynamic interactions and coherence between marine zooplankton and fishes linked to environmental variability

NASA Astrophysics Data System (ADS)

Liu, Hui; Fogarty, Michael J.; Hare, Jonathan A.; Hsieh, Chih-hao; Glaser, Sarah M.; Ye, Hao; Deyle, Ethan; Sugihara, George

2014-03-01

The dynamics of marine fishes are closely related to lower trophic levels and the environment. Quantitatively understanding ecosystem dynamics linking environmental variability and prey resources to exploited fishes is crucial for ecosystem-based management of marine living resources. However, standard statistical models typically grounded in the concept of linear system may fail to capture the complexity of ecological processes. We have attempted to model ecosystem dynamics using a flexible, nonparametric class of nonlinear forecasting models. We analyzed annual time series of four environmental indices, 22 marine copepod taxa, and four ecologically and commercially important fish species during 1977 to 2009 on Georges Bank, a highly productive and intensively studied area of the northeast U.S. continental shelf ecosystem. We examined the underlying dynamic features of environmental indices and copepods, quantified the dynamic interactions and coherence with fishes, and explored the potential control mechanisms of ecosystem dynamics from a nonlinear perspective. We found: (1) the dynamics of marine copepods and environmental indices exhibiting clear nonlinearity; (2) little evidence of complex dynamics across taxonomic levels of copepods; (3) strong dynamic interactions and coherence between copepods and fishes; and (4) the bottom-up forcing of fishes and top-down control of copepods coexisting as target trophic levels vary. These findings highlight the nonlinear interactions among ecosystem components and the importance of marine zooplankton to fish populations which point to two forcing mechanisms likely interactively regulating the ecosystem dynamics on Georges Bank under a changing environment.

Complexities of high temperature metal fatigue: Some steps toward understanding

NASA Technical Reports Server (NTRS)

Manson, S. S.; Halford, G. R.

1983-01-01

After pointing out many of the complexities that attend high temperature metal fatigue beyond those already studied in the sub-creep range, a description of the micromechanisms of deformation and fracture is presented for several classes of materials that were studied over the past dozen years. Strainrange Partitioning (SRP) is used as a framework for interpreting the results. Several generic types of behavior were observed with regard both to deformation and fracture and each is discussed in the context of the micromechanisms involved. Treatment of cumulative fatigue damage and the possibility of ""healing'' of damage in successive loading loops, has led to a new interpretation of the Interaction Damage Rule of SRP. Using the concept of ""equivalent micromechanistic damage'' -- that the same damage on a microscopic scale is induced if the same hysteresis loops are generated, element for element -- it turns out the Interaction Damage Rule essentially compounds a number of variants of hysteresis loops, all of which have the same damage according to SRP concepts, into a set of loops each containing only one of the generic SRP strainranges. Thus the damage associcated with complex loops comprising several types of strainrange is analyzed by considering a combination of loops each containing only one type of strainrange. This concept is expanded to show how several independent loops can combine to ""heal'' creep damage in a complex loading history.

Tellurite-exposed Escherichia coli exhibits increased intracellular {alpha}-ketoglutarate

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

Reinoso, Claudia A.; Auger, Christopher; Appanna, Vasu D.

2012-05-18

Highlights: Black-Right-Pointing-Pointer Tellurite-exposed E. coli exhibits decreased {alpha}-KG dehydrogenase activity. Black-Right-Pointing-Pointer Cells lacking {alpha}-KGDH genes are more sensitive to ROS than isogenic, wt E. coli. Black-Right-Pointing-Pointer KG accumulation may serve to face tellurite-mediated oxidative damage in E. coli. -- Abstract: The tellurium oxyanion tellurite is toxic to most organisms because of its ability to generate oxidative stress. However, the detailed mechanism(s) how this toxicant interferes with cellular processes have yet to be fully understood. As part of our effort to decipher the molecular interactions of tellurite with living systems, we have evaluated the global metabolism of {alpha}-ketoglutarate a known antioxidantmore » in Escherichia coli. Tellurite-exposed cells displayed reduced activity of the KG dehydrogenase complex (KGDHc), resulting in increased intracellular KG content. This complex's reduced activity seems to be due to decreased transcription in the stressed cells of sucA, a gene that encodes the E1 component of KGDHc. Furthermore, it was demonstrated that the increase in total reactive oxygen species and superoxide observed upon tellurite exposure was more evident in wild type cells than in E. coli with impaired KGDHc activity. These results indicate that KG may be playing a pivotal role in combating tellurite-mediated oxidative damage.« less

Silver(I) coordination polymers assembled from flexible cyclotriphosphazene ligand: structures, topologies and investigation of the counteranion effects.

PubMed

Davarcı, Derya; Gür, Rüştü; Beşli, Serap; Şenkuytu, Elif; Zorlu, Yunus

2016-06-01

The reactions of a flexible ligand hexakis(3-pyridyloxy)cyclotriphosphazene (HPCP) with a variety of silver(I) salts (AgX; X = NO3(-), PF6(-), ClO4(-), CH3PhSO3(-), BF4(-) and CF3SO3(-)) afforded six silver(I) coordination polymers, namely {[Ag2(HPCP)]·(NO3)2·H2O}n (1), {[Ag2(HPCP)(CH3CN)]·(PF6)2}n (2), {[Ag2(HPCP)(CH3CN)]·(ClO4)2}n (3), [Ag3(HPCP)(CH3PhSO3)3]n (4), [Ag2(HPCP)(CH3CN)(BF4)2]n (5) and {[Ag(HPCP)]·(CF3SO3)}n (6). All of the isolated crystalline compounds were structurally determined by X-ray crystallography. Changing the counteranions in the reactions, which were conducted under similar conditions of M/L ratio (1:1), temperature and solvent, resulted in structures with different types of topologies. In complexes (1)-(6), the ligand HPCP shows different coordination modes with Ag(I) ions giving two-dimensional layered structures and three-dimensional frameworks with different topologies. Complex (1) displays a new three-dimensional framework adopting a (3,3,6)-connected 3-nodal net with point symbol {4.6(2)}2{4(2).6(10).8(3)}. Complexes (2) and (3) are isomorphous and have a two-dimensional layered structure showing the same 3,6L60 topology with point symbol {4.2(6)}2{4(8).6(6).8}. Complex (4) is a two-dimensional structure incorporating short Ag...Ag argentophilic interactions and has a uninodal 4-connected sql/Shubnikov tetragonal plane net with {4(4).6(2)} topology. Complex (5) exhibits a novel three-dimensional framework and more suprisingly contains twofold interpenetrated honeycomb-like networks, in which the single net has a trinodal (2,3,5)-connected 3-nodal net with point symbol {6(3).8(6).12}{6(3)}{8}. Complex (6) crystallizes in a trigonal crystal system with the space group R\\bar 3 and possesses a three-dimensional polymeric structure showing a binodal (4,6)-connected fsh net with the point symbol (4(3).6(3))2.(4(6).6(6).8(3)). The effect of the counteranions on the formation of coordination polymers is discussed in this study.

S66: A Well-balanced Database of Benchmark Interaction Energies Relevant to Biomolecular Structures

PubMed Central

2011-01-01

With numerous new quantum chemistry methods being developed in recent years and the promise of even more new methods to be developed in the near future, it is clearly critical that highly accurate, well-balanced, reference data for many different atomic and molecular properties be available for the parametrization and validation of these methods. One area of research that is of particular importance in many areas of chemistry, biology, and material science is the study of noncovalent interactions. Because these interactions are often strongly influenced by correlation effects, it is necessary to use computationally expensive high-order wave function methods to describe them accurately. Here, we present a large new database of interaction energies calculated using an accurate CCSD(T)/CBS scheme. Data are presented for 66 molecular complexes, at their reference equilibrium geometries and at 8 points systematically exploring their dissociation curves; in total, the database contains 594 points: 66 at equilibrium geometries, and 528 in dissociation curves. The data set is designed to cover the most common types of noncovalent interactions in biomolecules, while keeping a balanced representation of dispersion and electrostatic contributions. The data set is therefore well suited for testing and development of methods applicable to bioorganic systems. In addition to the benchmark CCSD(T) results, we also provide decompositions of the interaction energies by means of DFT-SAPT calculations. The data set was used to test several correlated QM methods, including those parametrized specifically for noncovalent interactions. Among these, the SCS-MI-CCSD method outperforms all other tested methods, with a root-mean-square error of 0.08 kcal/mol for the S66 data set. PMID:21836824

Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3.

PubMed

Leettola, Catherine N; Knight, Mary Jane; Cascio, Duilio; Hoffman, Sigrid; Bowie, James U

2014-07-07

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder leading to end-stage renal failure in humans. In the PKD/Mhm(cy/+) rat model of ADPKD, the point mutation R823W in the sterile alpha motif (SAM) domain of the protein ANKS6 is responsible for disease. SAM domains are known protein-protein interaction domains, capable of binding each other to form polymers and heterodimers. Despite its physiological importance, little is known about the function of ANKS6 and how the R823W point mutation leads to PKD. Recent work has revealed that ANKS6 interacts with a related protein called ANKS3. Both ANKS6 and ANKS3 have a similar domain structure, with ankyrin repeats at the N-terminus and a SAM domain at the C-terminus. The SAM domain of ANKS3 is identified as a direct binding partner of the ANKS6 SAM domain. We find that ANKS3-SAM polymerizes and ANKS6-SAM can bind to one end of the polymer. We present crystal structures of both the ANKS3-SAM polymer and the ANKS3-SAM/ANKS6-SAM complex, revealing the molecular details of their association. We also learn how the R823W mutation disrupts ANKS6 function by dramatically destabilizing the SAM domain such that the interaction with ANKS3-SAM is lost. ANKS3 is a direct interacting partner of ANKS6. By structurally and biochemically characterizing the interaction between the ANKS3 and ANKS6 SAM domains, our work provides a basis for future investigation of how the interaction between these proteins mediates kidney function.

Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3

PubMed Central

2014-01-01

Background Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder leading to end-stage renal failure in humans. In the PKD/Mhm(cy/+) rat model of ADPKD, the point mutation R823W in the sterile alpha motif (SAM) domain of the protein ANKS6 is responsible for disease. SAM domains are known protein-protein interaction domains, capable of binding each other to form polymers and heterodimers. Despite its physiological importance, little is known about the function of ANKS6 and how the R823W point mutation leads to PKD. Recent work has revealed that ANKS6 interacts with a related protein called ANKS3. Both ANKS6 and ANKS3 have a similar domain structure, with ankyrin repeats at the N-terminus and a SAM domain at the C-terminus. Results The SAM domain of ANKS3 is identified as a direct binding partner of the ANKS6 SAM domain. We find that ANKS3-SAM polymerizes and ANKS6-SAM can bind to one end of the polymer. We present crystal structures of both the ANKS3-SAM polymer and the ANKS3-SAM/ANKS6-SAM complex, revealing the molecular details of their association. We also learn how the R823W mutation disrupts ANKS6 function by dramatically destabilizing the SAM domain such that the interaction with ANKS3-SAM is lost. Conclusions ANKS3 is a direct interacting partner of ANKS6. By structurally and biochemically characterizing the interaction between the ANKS3 and ANKS6 SAM domains, our work provides a basis for future investigation of how the interaction between these proteins mediates kidney function. PMID:24998259

Electron and Ion Reactions in Molecular Solids: from astrochemistry to radiobiology

NASA Astrophysics Data System (ADS)

Huels, Michael A.

2001-05-01

Wherever ionizing radiation interacts with matter, it initiates reaction cascades involving ions, radicals, and ballistic secondary electrons; these reactions occur on fs time-scales, and may lead to substantial physical and chemical modifications of a medium. Here I present measurements of 0-80 eV electron and ion reactions in condensed films ranging from simple to complex, and astrophysical to biological in nature. Targets contain either: small molecules, hydrocarbons of increasing complexity (incl. bases, sugars, single/double stranded DNA), molecules on rare gas matrices, or mixed cryogenic films resembling astrophysical or planetary surface ices containing O2, H2O, methane, and aromatic hydrocarbons. The basic electron or ion reaction mechanisms and pathways are found to be fundamentally universal, but are modulated by the physical and chemical nature of the medium; depending on the latter, a reaction cascade may lead to different end-points, e.g. a decrease in molecular complexity via molecular fragmentations, or increases in complexity via secondary ion collision induced synthesis of larger molecules in hydrocarbon rich surface ices.

Origin of attraction in p-benzoquinone complexes with benzene and p-hydroquinone.

PubMed

Tsuzuki, Seiji; Uchimaru, Tadafumi; Ono, Taizo

2017-08-30

The origin of the attraction in charge-transfer complexes (a p-hydroquinone-p-benzoquinone complex and benzene complexes with benzoquinone, tetracyanoethylene and Br 2 ) was analyzed using distributed multipole analysis and symmetry-adapted perturbation theory. Both methods show that the dispersion interactions are the primary source of the attraction in these charge-transfer complexes followed by the electrostatic interactions. The natures of the intermolecular interactions in these complexes are close to the π/π interactions of neutral aromatic molecules. The electrostatic interactions play important roles in determining the magnitude of the attraction. The contribution of charge-transfer interactions to the attraction is not large compared with the dispersion interactions in these complexes.

Logic-Based Models for the Analysis of Cell Signaling Networks†

PubMed Central

2010-01-01

Computational models are increasingly used to analyze the operation of complex biochemical networks, including those involved in cell signaling networks. Here we review recent advances in applying logic-based modeling to mammalian cell biology. Logic-based models represent biomolecular networks in a simple and intuitive manner without describing the detailed biochemistry of each interaction. A brief description of several logic-based modeling methods is followed by six case studies that demonstrate biological questions recently addressed using logic-based models and point to potential advances in model formalisms and training procedures that promise to enhance the utility of logic-based methods for studying the relationship between environmental inputs and phenotypic or signaling state outputs of complex signaling networks. PMID:20225868

Magnetically tunable 1D Coulomb drag: Theory

NASA Astrophysics Data System (ADS)

Tylan-Tyler, Anthony; Tang, Yuhe; Levy, Jeremy

In this work, we examine the Coulomb drag effect in 1D nanowires in close proximity, focusing on experimental parameters relevant to complex-oxide nanostructures. Previous work on this problem examined Coulomb drag through quantum point contacts, where effective capacitive coupling between the 2D leads of the system generates the drag voltage. In our case, the entire system is composed of 1D components and thus a more careful treatment of the Coulomb interactions is required. This more complex environment then leads to the ability to switch the drag voltage by an applied magnetic field without altering the current supplied to the drive system. We gratefully acknowledge financial support from ONR N00014-15-1-2847 and DOE DE-SC0014417.

Genes for normal sleep and sleep disorders.

PubMed

Tafti, Mehdi; Maret, Stéphanie; Dauvilliers, Yves

2005-01-01

Sleep and wakefulness are complex behaviors that are influenced by many genetic and environmental factors, which are beginning to be discovered. The contribution of genetic components to sleep disorders is also increasingly recognized as important. Point mutations in the prion protein, period 2, and the prepro-hypocretin/orexin gene have been found as the cause of a few sleep disorders but the possibility that other gene defects may contribute to the pathophysiology of major sleep disorders is worth in-depth investigations. However, single gene disorders are rare and most common disorders are complex in terms of their genetic susceptibility, environmental effects, gene-gene, and gene-environment interactions. We review here the current progress in the genetics of normal and pathological sleep.

Exploring the Interaction Mechanism Between Cyclopeptide DC3 and Androgen Receptor Using Molecular Dynamics Simulations and Free Energy Calculations

PubMed Central

Zhang, Huimin; Song, Tianqing; Yang, Yizhao; Fu, Chenggong; Li, Jiazhong

2018-01-01

Androgen receptor (AR) is a key target in the discovery of anti-PCa (Prostate Cancer) drugs. Recently, a novel cyclopeptide Diffusa Cyclotide-3 (DC3), isolated from Hedyotisdiffusa, has been experimentally demonstrated to inhibit the survival and growth of LNCap cells, which typically express T877A-mutated AR, the most frequently detected point mutation of AR in castration-resistant prostate cancer (CRPC). But the interaction mechanism between DC3 and AR is not clear. Here in this study we aim to explore the possible binding mode of DC3 to T877A-mutated AR from molecular perspective. Firstly, homology modeling was employed to construct the three-dimensional structure of the cyclopeptide DC3 using 2kux.1.A as the template. Then molecular docking, molecular dynamics (MD) simulations, and molecular mechanics/generalized Born surface area (MM-GBSA) methods were performed to determine the bind site and explore the detailed interaction mechanism of DC3-AR complex. The obtained results suggested that the site formed by H11, loop888-893, and H12 (site 2) was the most possible position of DC3 binding to AR. Besides, hydrogen bonds, hydrophobic, and electrostatic interactions play dominant roles in the recognition and combination of DC3-AR complex. The essential residues dominant in each interaction were specifically revealed. This work facilitates our understanding of the interaction mechanism of DC3 binding to AR at the molecular level and contributes to the rational cyclopeptide drug design for prostate cancer. PMID:29755968

Exploring the Interaction Mechanism between Cyclopeptide DC3 and Androgen Receptor Using Molecular Dynamics Simulations and Free Energy Calculations

NASA Astrophysics Data System (ADS)

Zhang, Huimin; Song, Tianqing; Yang, Yizhao; Fu, Chenggong; Li, Jiazhong

2018-04-01

Androgen receptor (AR) is a key target in the discovery of anti-PCa (Prostate Cancer) drugs. Recently, a novel cyclopeptide Diffusa Cyclotide-3 (DC3), isolated from Hedyotisdiffusa, has been experimentally demonstrated to inhibit the survival and growth of LNCap cells, which typically express T877A-mutated AR, the most frequently detected point mutation of AR in castration-resistant prostate cancer (CRPC). But the interaction mechanism between DC3 and AR is not clear. Here in this study we aim to explore the possible binding mode of DC3 to T877A-mutated AR from molecular perspective. Firstly, homology modeling was employed to construct the three-dimensional structure of the cyclopeptide DC3 using 2kux.1.A as the template. Then molecular docking, molecular dynamics (MD) simulations and molecular mechanics/generalized Born surface area (MM-GBSA) methods were performed to determine the bind site and explore the detailed interaction mechanism of DC3-AR complex. The obtained results suggested that the site formed by H11, loop888-893 and H12 (site 2) was the most possible position of DC3 binding to AR. Besides, hydrogen bonds, hydrophobic and electrostatic interactions play dominant roles in the recognition and combination of DC3-AR complex. The essential residues dominant in each interaction were specifically revealed. This work facilitates our understanding of the interaction mechanism of DC3 binding to AR at the molecular level and contributes to the rational cyclopeptide drug design for prostate cancer.

Exploring the Interaction Mechanism Between Cyclopeptide DC3 and Androgen Receptor Using Molecular Dynamics Simulations and Free Energy Calculations.

PubMed

Zhang, Huimin; Song, Tianqing; Yang, Yizhao; Fu, Chenggong; Li, Jiazhong

2018-01-01

Androgen receptor (AR) is a key target in the discovery of anti-PCa (Prostate Cancer) drugs. Recently, a novel cyclopeptide Diffusa Cyclotide-3 (DC3), isolated from Hedyotisdiffusa , has been experimentally demonstrated to inhibit the survival and growth of LNCap cells, which typically express T877A-mutated AR, the most frequently detected point mutation of AR in castration-resistant prostate cancer (CRPC). But the interaction mechanism between DC3 and AR is not clear. Here in this study we aim to explore the possible binding mode of DC3 to T877A-mutated AR from molecular perspective. Firstly, homology modeling was employed to construct the three-dimensional structure of the cyclopeptide DC3 using 2kux.1.A as the template. Then molecular docking, molecular dynamics (MD) simulations, and molecular mechanics/generalized Born surface area (MM-GBSA) methods were performed to determine the bind site and explore the detailed interaction mechanism of DC3-AR complex. The obtained results suggested that the site formed by H11, loop888-893, and H12 (site 2) was the most possible position of DC3 binding to AR. Besides, hydrogen bonds, hydrophobic, and electrostatic interactions play dominant roles in the recognition and combination of DC3-AR complex. The essential residues dominant in each interaction were specifically revealed. This work facilitates our understanding of the interaction mechanism of DC3 binding to AR at the molecular level and contributes to the rational cyclopeptide drug design for prostate cancer.

S/G-1: an ab initio force-field blending frozen Hermite Gaussian densities and distributed multipoles. Proof of concept and first applications to metal cations.

PubMed

Chaudret, Robin; Gresh, Nohad; Narth, Christophe; Lagardère, Louis; Darden, Thomas A; Cisneros, G Andrés; Piquemal, Jean-Philip

2014-09-04

We demonstrate as a proof of principle the capabilities of a novel hybrid MM'/MM polarizable force field to integrate short-range quantum effects in molecular mechanics (MM) through the use of Gaussian electrostatics. This lead to a further gain in accuracy in the representation of the first coordination shell of metal ions. It uses advanced electrostatics and couples two point dipole polarizable force fields, namely, the Gaussian electrostatic model (GEM), a model based on density fitting, which uses fitted electronic densities to evaluate nonbonded interactions, and SIBFA (sum of interactions between fragments ab initio computed), which resorts to distributed multipoles. To understand the benefits of the use of Gaussian electrostatics, we evaluate first the accuracy of GEM, which is a pure density-based Gaussian electrostatics model on a test Ca(II)-H2O complex. GEM is shown to further improve the agreement of MM polarization with ab initio reference results. Indeed, GEM introduces nonclassical effects by modeling the short-range quantum behavior of electric fields and therefore enables a straightforward (and selective) inclusion of the sole overlap-dependent exchange-polarization repulsive contribution by means of a Gaussian damping function acting on the GEM fields. The S/G-1 scheme is then introduced. Upon limiting the use of Gaussian electrostatics to metal centers only, it is shown to be able to capture the dominant quantum effects at play on the metal coordination sphere. S/G-1 is able to accurately reproduce ab initio total interaction energies within closed-shell metal complexes regarding each individual contribution including the separate contributions of induction, polarization, and charge-transfer. Applications of the method are provided for various systems including the HIV-1 NCp7-Zn(II) metalloprotein. S/G-1 is then extended to heavy metal complexes. Tested on Hg(II) water complexes, S/G-1 is shown to accurately model polarization up to quadrupolar response level. This opens up the possibility of embodying explicit scalar relativistic effects in molecular mechanics thanks to the direct transferability of ab initio pseudopotentials. Therefore, incorporating GEM-like electron density for a metal cation enable the introduction of nonambiguous short-range quantum effects within any point-dipole based polarizable force field without the need of an extensive parametrization.

Unraveling dynamics of human physical activity patterns in chronic pain conditions

NASA Astrophysics Data System (ADS)

Paraschiv-Ionescu, Anisoara; Buchser, Eric; Aminian, Kamiar

2013-06-01

Chronic pain is a complex disabling experience that negatively affects the cognitive, affective and physical functions as well as behavior. Although the interaction between chronic pain and physical functioning is a well-accepted paradigm in clinical research, the understanding of how pain affects individuals' daily life behavior remains a challenging task. Here we develop a methodological framework allowing to objectively document disruptive pain related interferences on real-life physical activity. The results reveal that meaningful information is contained in the temporal dynamics of activity patterns and an analytical model based on the theory of bivariate point processes can be used to describe physical activity behavior. The model parameters capture the dynamic interdependence between periods and events and determine a `signature' of activity pattern. The study is likely to contribute to the clinical understanding of complex pain/disease-related behaviors and establish a unified mathematical framework to quantify the complex dynamics of various human activities.

Hypothalamic Survival Circuits: Blueprints for Purposive Behaviors

PubMed Central

Sternson, Scott M.

2015-01-01

Neural processes that direct an animal’s actions toward environmental goals are critical elements for understanding behavior. The hypothalamus is closely associated with motivated behaviors required for survival and reproduction. Intense feeding, drinking, aggressive, and sexual behaviors can be produced by a simple neuronal stimulus applied to discrete hypothalamic regions. What can these “evoked behaviors” teach us about the neural processes that determine behavioral intent and intensity? Small populations of neurons sufficient to evoke a complex motivated behavior may be used as entry points to identify circuits that energize and direct behavior to specific goals. Here, I review recent applications of molecular genetic, optogenetic, and pharmacogenetic approaches that overcome previous limitations for analyzing anatomically complex hypothalamic circuits and their interactions with the rest of the brain. These new tools have the potential to bridge the gaps between neurobiological and psychological thinking about the mechanisms of complex motivated behavior. PMID:23473313

Hypothalamic survival circuits: blueprints for purposive behaviors.

PubMed

Sternson, Scott M

2013-03-06

Neural processes that direct an animal's actions toward environmental goals are critical elements for understanding behavior. The hypothalamus is closely associated with motivated behaviors required for survival and reproduction. Intense feeding, drinking, aggressive, and sexual behaviors can be produced by a simple neuronal stimulus applied to discrete hypothalamic regions. What can these "evoked behaviors" teach us about the neural processes that determine behavioral intent and intensity? Small populations of neurons sufficient to evoke a complex motivated behavior may be used as entry points to identify circuits that energize and direct behavior to specific goals. Here, I review recent applications of molecular genetic, optogenetic, and pharmacogenetic approaches that overcome previous limitations for analyzing anatomically complex hypothalamic circuits and their interactions with the rest of the brain. These new tools have the potential to bridge the gaps between neurobiological and psychological thinking about the mechanisms of complex motivated behavior. Copyright © 2013 Elsevier Inc. All rights reserved.

The AICD interacting protein DAB1 is up-regulated in Alzheimer frontal cortex brain samples and causes deregulation of proteins involved in gene expression changes.

PubMed

Müller, T; Loosse, C; Schrötter, A; Schnabel, A; Helling, S; Egensperger, R; Marcus, K

2011-08-01

AICD is the intracellular subdomain of the amyloid precursor protein thought to play a pivotal role as a potential transcription factor that might be of relevance for the pathophysiology of Alzheimer's disease. For its signal transduction potential AICD requires interacting proteins like FE65 and TIP60. However, many other proteins were described being able to bind to AICD. Here, we studied mRNA levels of AICD interacting proteins and found one of them (DAB1) strongly up-regulated in human post-mortem frontal cortex brain samples of AD patients. Subsequent cell culture experiments revealed that elevated DAB1 level results in the deregulation of the cellular proteome. We found the proliferation associated protein 2G4 as well as the guanine monophosphate synthetase (GMPS) significantly up-regulated in DAB1 over-expressing cells. Both proteins can be involved in cellular transcription processes supporting the hypothesis that DAB1 acts via modification of the AICD-dependent transcriptionally active complex. Of note, expression of the three components of the putative transcription complex (AICD, FE65, and TIP60 (AFT)) also revealed deregulation of the GMPS protein in an opposite fashion. Our results point to a putative relevance of AICD-dependent mechanisms in AD, caused by protein abundance changes of AICD interacting proteins, as shown for DAB1 in this work.

Molecular modeling of class I and II alleles of the major histocompatibility complex in Salmo salar.

PubMed

Cárdenas, Constanza; Bidon-Chanal, Axel; Conejeros, Pablo; Arenas, Gloria; Marshall, Sergio; Luque, F Javier

2010-12-01

Knowledge of the 3D structure of the binding groove of major histocompatibility (MHC) molecules, which play a central role in the immune response, is crucial to shed light into the details of peptide recognition and polymorphism. This work reports molecular modeling studies aimed at providing 3D models for two class I and two class II MHC alleles from Salmo salar (Sasa), as the lack of experimental structures of fish MHC molecules represents a serious limitation to understand the specific preferences for peptide binding. The reliability of the structural models built up using bioinformatic tools was explored by means of molecular dynamics simulations of their complexes with representative peptides, and the energetics of the MHC-peptide interaction was determined by combining molecular mechanics interaction energies and implicit continuum solvation calculations. The structural models revealed the occurrence of notable differences in the nature of residues at specific positions in the binding groove not only between human and Sasa MHC proteins, but also between different Sasa alleles. Those differences lead to distinct trends in the structural features that mediate the binding of peptides to both class I and II MHC molecules, which are qualitatively reflected in the relative binding affinities. Overall, the structural models presented here are a valuable starting point to explore the interactions between MHC receptors and pathogen-specific interactions and to design vaccines against viral pathogens.

Ab initio theory of point defects in oxide materials: structure, properties, chemical reactivity

NASA Astrophysics Data System (ADS)

Pacchioni, Gianfranco

2000-05-01

Point defects play a fundamental role in determining the physical and chemical properties of inorganic materials. This holds not only for the bulk properties but also for the surface of oxides where several kinds of point defects exist and exhibit a rich and complex chemistry. A particularly important defect in oxides is the oxygen vacancy. Depending on the electronic structure of the material the nature of oxygen vacancies changes dramatically. In this article we provide a rationalization of the very different electronic structure of neutral and charged oxygen vacancies in SiO 2 and MgO, two oxide materials with completely different electronic structure (from very ionic, MgO, to largely covalent, SiO 2). We used methods of ab initio quantum chemistry, from density functional theory (DFT) to configuration interaction (CI), to determine the ground and excited state properties of these defects. The theoretical results are combined with recent spectroscopic measurements. A series of observable properties has been determined in this way: defect formation energies, hyperfine interactions in electron paramagnetic resonance (EPR) spectra of paramagnetic centers, optical spectra, surface chemical reactivity. The interplay between experimental and theoretical information allows one to unambiguously identify the structure of oxygen vacancies in these binary oxides and on their surfaces.

Dynamic topology and flux rope evolution during non-linear tearing of 3D null point current sheets

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

Wyper, P. F., E-mail: peterw@maths.dundee.ac.uk; Pontin, D. I., E-mail: dpontin@maths.dundee.ac.uk

2014-10-15

In this work, the dynamic magnetic field within a tearing-unstable three-dimensional current sheet about a magnetic null point is described in detail. We focus on the evolution of the magnetic null points and flux ropes that are formed during the tearing process. Generally, we find that both magnetic structures are created prolifically within the layer and are non-trivially related. We examine how nulls are created and annihilated during bifurcation processes, and describe how they evolve within the current layer. The type of null bifurcation first observed is associated with the formation of pairs of flux ropes within the current layer.more » We also find that new nulls form within these flux ropes, both following internal reconnection and as adjacent flux ropes interact. The flux ropes exhibit a complex evolution, driven by a combination of ideal kinking and their interaction with the outflow jets from the main layer. The finite size of the unstable layer also allows us to consider the wider effects of flux rope generation. We find that the unstable current layer acts as a source of torsional magnetohydrodynamic waves and dynamic braiding of magnetic fields. The implications of these results to several areas of heliophysics are discussed.« less

A novel, rapid and automated conductometric method to evaluate surfactant-cells interactions by means of critical micellar concentration analysis.

PubMed

Tiecco, Matteo; Corte, Laura; Roscini, Luca; Colabella, Claudia; Germani, Raimondo; Cardinali, Gianluigi

2014-07-25

Conductometry is widely used to determine critical micellar concentration and micellar aggregates surface properties of amphiphiles. Current conductivity experiments of surfactant solutions are typically carried out by manual pipetting, yielding some tens reading points within a couple of hours. In order to study the properties of surfactant-cells interactions, each amphiphile must be tested in different conditions against several types of cells. This calls for complex experimental designs making the application of current methods seriously time consuming, especially because long experiments risk to determine alterations of cells, independently of the surfactant action. In this paper we present a novel, accurate and rapid automated procedure to obtain conductometric curves with several hundreds reading points within tens of minutes. The method was validated with surfactant solutions alone and in combination with Saccharomyces cerevisiae cells. An easy-to use R script, calculates conductometric parameters and their statistical significance with a graphic interface to visualize data and results. The validations showed that indeed the procedure works in the same manner with surfactant alone or in combination with cells, yielding around 1000 reading points within 20 min and with high accuracy, as determined by the regression analysis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Navier-Stokes and viscous-inviscid interaction

NASA Technical Reports Server (NTRS)

Steger, Joseph L.; Vandalsem, William R.

1989-01-01

Some considerations toward developing numerical procedures for simulating viscous compressible flows are discussed. Both Navier-Stokes and boundary layer field methods are considered. Because efficient viscous-inviscid interaction methods have been difficult to extend to complex 3-D flow simulations, Navier-Stokes procedures are more frequently being utilized even though they require considerably more work per grid point. It would seem a mistake, however, not to make use of the more efficient approximate methods in those regions in which they are clearly valid. Ideally, a general purpose compressible flow solver that can optionally take advantage of approximate solution methods would suffice, both to improve accuracy and efficiency. Some potentially useful steps toward this goal are described: a generalized 3-D boundary layer formulation and the fortified Navier-Stokes procedure.

On the temperature-dependent exchange splitting in the quasiparticle bandstructure of Ni

NASA Astrophysics Data System (ADS)

Borgiel, W.; Nolting, W.; Donath, M.

1989-11-01

A theoretical model for the bandferromagnet Ni is proposed, which takes into account the intraatomic electron interactions within the d band complex. After introducing effective spin operators the model-Hamiltonian consists of a one-particle part, an intraband interaction of Hubbard-type, and an interband exchange, formally describing electron magnon scattering (s-f model). The one particle energies are taken from a realistic bandstructure calculation for paramagnetic Ni. We use a many body procedure for a detailed inspection of the quasiparticle bandstructure in KX and XW directions, present the corresponding spectral densities, and compare the temperature dependent exchange splittings near the X and W point with recent results from spin resolved photoemission (PE) - and inverse photoemission (IPE) - experiments.

Environmental Microbial Community Proteomics: Status, Challenges and Perspectives.

PubMed

Wang, Da-Zhi; Kong, Ling-Fen; Li, Yuan-Yuan; Xie, Zhang-Xian

2016-08-05

Microbial community proteomics, also termed metaproteomics, is an emerging field within the area of microbiology, which studies the entire protein complement recovered directly from a complex environmental microbial community at a given point in time. Although it is still in its infancy, microbial community proteomics has shown its powerful potential in exploring microbial diversity, metabolic potential, ecological function and microbe-environment interactions. In this paper, we review recent advances achieved in microbial community proteomics conducted in diverse environments, such as marine and freshwater, sediment and soil, activated sludge, acid mine drainage biofilms and symbiotic communities. The challenges facing microbial community proteomics are also discussed, and we believe that microbial community proteomics will greatly enhance our understanding of the microbial world and its interactions with the environment.

Complex interactions between diapirs and 4-D subduction driven mantle wedge circulation.

NASA Astrophysics Data System (ADS)

Sylvia, R. T.; Kincaid, C. R.

2015-12-01

Analogue laboratory experiments generate 4-D flow of mantle wedge fluid and capture the evolution of buoyant mesoscale diapirs. The mantle is modeled with viscous glucose syrup with an Arrhenius type temperature dependent viscosity. To characterize diapir evolution we experiment with a variety of fluids injected from multiple point sources. Diapirs interact with kinematically induced flow fields forced by subducting plate motions replicating a range of styles observed in dynamic subduction models (e.g., rollback, steepening, gaps). Data is collected using high definition timelapse photography and quantified using image velocimetry techniques. While many studies assume direct vertical connections between the volcanic arc and the deeper mantle source region, our experiments demonstrate the difficulty of creating near vertical conduits. Results highlight extreme curvature of diapir rise paths. Trench-normal deflection occurs as diapirs are advected downward away from the trench before ascending into wedge apex directed return flow. Trench parallel deflections up to 75% of trench length are seen in all cases, exacerbated by complex geometry and rollback motion. Interdiapir interaction is also important; upwellings with similar trajectory coalesce and rapidly accelerate. Moreover, we observe a new mode of interaction whereby recycled diapir material is drawn down along the slab surface and then initiates rapid fluid migration updip along the slab-wedge interface. Variability in trajectory and residence time leads to complex petrologic inferences. Material from disparate source regions can surface at the same location, mix in the wedge, or become fully entrained in creeping flow adding heterogeneity to the mantle. Active diapirism or any other vertical fluid flux mechanism employing rheological weakening lowers viscosity in the recycling mantle wedge affecting both solid and fluid flow characteristics. Many interesting and insightful results have been presented based upon 2-D, steady-state thermal and flow regimes. We reiterate the importance of 4-D time evolution in subduction models. Analogue experiments allow added feedbacks and complexity improving intuition and providing insight for further investigation.

Identification and super-resolution imaging of ligand-activated receptor dimers in live cells

NASA Astrophysics Data System (ADS)

Winckler, Pascale; Lartigue, Lydia; Giannone, Gregory; de Giorgi, Francesca; Ichas, François; Sibarita, Jean-Baptiste; Lounis, Brahim; Cognet, Laurent

2013-08-01

Molecular interactions are key to many chemical and biological processes like protein function. In many signaling processes they occur in sub-cellular areas displaying nanoscale organizations and involving molecular assemblies. The nanometric dimensions and the dynamic nature of the interactions make their investigations complex in live cells. While super-resolution fluorescence microscopies offer live-cell molecular imaging with sub-wavelength resolutions, they lack specificity for distinguishing interacting molecule populations. Here we combine super-resolution microscopy and single-molecule Förster Resonance Energy Transfer (FRET) to identify dimers of receptors induced by ligand binding and provide super-resolved images of their membrane distribution in live cells. By developing a two-color universal-Point-Accumulation-In-the-Nanoscale-Topography (uPAINT) method, dimers of epidermal growth factor receptors (EGFR) activated by EGF are studied at ultra-high densities, revealing preferential cell-edge sub-localization. This methodology which is specifically devoted to the study of molecules in interaction, may find other applications in biological systems where understanding of molecular organization is crucial.

Conceptual recurrence plots: revealing patterns in human discourse.

PubMed

Angus, Daniel; Smith, Andrew; Wiles, Janet

2012-06-01

Human discourse contains a rich mixture of conceptual information. Visualization of the global and local patterns within this data stream is a complex and challenging problem. Recurrence plots are an information visualization technique that can reveal trends and features in complex time series data. The recurrence plot technique works by measuring the similarity of points in a time series to all other points in the same time series and plotting the results in two dimensions. Previous studies have applied recurrence plotting techniques to textual data; however, these approaches plot recurrence using term-based similarity rather than conceptual similarity of the text. We introduce conceptual recurrence plots, which use a model of language to measure similarity between pairs of text utterances, and the similarity of all utterances is measured and displayed. In this paper, we explore how the descriptive power of the recurrence plotting technique can be used to discover patterns of interaction across a series of conversation transcripts. The results suggest that the conceptual recurrence plotting technique is a useful tool for exploring the structure of human discourse.

New cardioprotective agent flokalin and its supramolecular complexes with target amino acids: An integrated mass-spectrometry and quantum-chemical study

NASA Astrophysics Data System (ADS)

Pashynska, Vlada; Stepanian, Stepan; Gömöry, Ágnes; Vékey, Károly; Adamowicz, Ludwik

2017-10-01

This study is devoted to examining the molecular structure and molecular mechanisms of action of the recently developed cardioprotective agent flokalin (Fl), a fluorine containing analogue of pinacidil, which is known as an activator of ATP sensitive potassium membrane channels. A combined experimental and computational investigation of flokalin and its biologically relevant supramolecular complexes with selected amino acids involved in KATP-channels proteins is performed by electrospray ionization mass spectrometry (ESI MS) and by B3LYP/aug-cc-pVDZ quantum-mechanical calculations. First Fl solution is probed by ESI MS and a characteristic mass spectrum of the agent is obtained. Next the intermolecular interactions of Fl with the potentially targeted aminoacids (AA), Lys and Thr, are experimentally investigated. The spectra of the model Fl:AA systems (in 1:1 M ratio) contain information on the ions characteristic to the individual components of the mixtures; though the most interesting spectral results from the biophysical view point are related to the ions of stable molecular clusters formed by flokalin with AA. The peaks of such ions are quite prominent in the spectrum for the Fl:Lys system and less prominent for Fl:Thr. The equilibrium geometries and the corresponding interaction energies of the noncovalent supramolecular complexes registered in the mass spectra are determined in the quantum chemical calculations. The formation of the stable noncovalent complexes of Fl with Lyz and Thr revealed by the ESI MS probing and by the theoretical modelling testify to a possibility of interaction of flokalin with the KATP-channel domains enriched with the two amino acids in biological systems.

Surface complexation of carboxylate adheres Cryptosporidium parvum öocysts to the hematite-water interface

USGS Publications Warehouse

Gao, X.; Metge, D.W.; Ray, C.; Harvey, R.W.; Chorover, J.

2009-01-01

The interaction of viable Cryptosporidium parvum öocysts at the hematite (α-Fe2O3)−water interface was examined over a wide range in solution chemistry using in situ attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Spectra for hematite-sorbed öocysts showed distinct changes in carboxylate group vibrations relative to spectra obtained in the absence of hematite, indicative of direct chemical bonding between carboxylate groups and Fe metal centers of the hematite surface. The data also indicate that complexation modes vary with solution chemistry. In NaCl solution, öocysts are bound to hematite via monodentate and binuclear bidentate complexes. The former predominates at low pH, whereas the latter becomes increasingly prevalent with increasing pH. In a CaCl2 solution, only binuclear bidentate complexes are observed. When solution pH is above the point of zero net proton charge (PZNPC) of hematite, öocyst surface carboxylate groups are bound to the mineral surface via outer-sphere complexes in both electrolyte solutions.

Crystal structures of the CPAP/STIL complex reveal its role in centriole assembly and human microcephaly

PubMed Central

Cottee, Matthew A; Muschalik, Nadine; Wong, Yao Liang; Johnson, Christopher M; Johnson, Steven; Andreeva, Antonina; Oegema, Karen; Lea, Susan M; Raff, Jordan W; van Breugel, Mark

2013-01-01

Centrioles organise centrosomes and template cilia and flagella. Several centriole and centrosome proteins have been linked to microcephaly (MCPH), a neuro-developmental disease associated with small brain size. CPAP (MCPH6) and STIL (MCPH7) are required for centriole assembly, but it is unclear how mutations in them lead to microcephaly. We show that the TCP domain of CPAP constitutes a novel proline recognition domain that forms a 1:1 complex with a short, highly conserved target motif in STIL. Crystal structures of this complex reveal an unusual, all-β structure adopted by the TCP domain and explain how a microcephaly mutation in CPAP compromises complex formation. Through point mutations, we demonstrate that complex formation is essential for centriole duplication in vivo. Our studies provide the first structural insight into how the malfunction of centriole proteins results in human disease and also reveal that the CPAP–STIL interaction constitutes a conserved key step in centriole biogenesis. DOI: http://dx.doi.org/10.7554/eLife.01071.001 PMID:24052813

Dynamic interactions of proteins in complex networks

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

Appella, E.; Anderson, C.

2009-10-01

Recent advances in techniques such as NMR and EPR spectroscopy have enabled the elucidation of how proteins undergo structural changes to act in concert in complex networks. The three minireviews in this series highlight current findings and the capabilities of new methodologies for unraveling the dynamic changes controlling diverse cellular functions. They represent a sampling of the cutting-edge research presented at the 17th Meeting of Methods in Protein Structure Analysis, MPSA2008, in Sapporo, Japan, 26-29 August, 2008 (http://www.iapsap.bnl.gov). The first minireview, by Christensen and Klevit, reports on a structure-based yeast two-hybrid method for identifying E2 ubiquitin-conjugating enzymes that interact withmore » the E3 BRCA1/BARD1 heterodimer ligase to generate either mono- or polyubiquitinated products. This method demonstrated for the first time that the BRCA1/BARD1 E3 can interact with 10 different E2 enzymes. Interestingly, the interaction with multiple E2 enzymes displayed unique ubiquitin-transfer properties, a feature expected to be common among other RING and U-box E3s. Further characterization of new E3 ligases and the E2 enzymes that interact with them will greatly enhance our understanding of ubiquitin transfer and facilitate studies of roles of ubiquitin and ubiquitin-like proteins in protein processing and trafficking. Stein et al., in the second minireview, describe recent progress in defining the binding specificity of different peptide-binding domains. The authors clearly point out that transient peptide interactions mediated by both post-translational modifications and disordered regions ensure a high level of specificity. They postulate that a regulatory code may dictate the number of combinations of domains and post-translational modifications needed to achieve the required level of interaction specificity. Moreover, recognition alone is not enough to obtain a stable complex, especially in a complex cellular environment. Increasing evidence indicates that disordered domains can acquire structural features that modulate the binding and strength of the signaling cascade. Whereas the first two minireviews describe ways in which protein interactions are modulated, the third, by Tompa, focuses on the importance of protein disorder in a subset of amyloid proteins. It is apparent that within this group, part of the polypeptide chain remains disordered during amyloid formation. Moreover, the disordered segments have different amino acid composition and physicochemical characteristics, which suggests that they may play a role in amyloid stability. The disordered region may serve as a linker to connect the ordered core and a globular domain, maintaining the stability and structure of the globular domain and minimizing protein refolding upon amyloid formation. As techniques in protein chemistry advance, we are learning more and more about the mechanisms that regulate and are regulated by protein interactions. The three minireviews in this series offer a glimpse of the complex dynamics fundamental to protein-protein interactions. In the future, we expect that the knowledge gained will help to augment our ability to control complex pathologies and treat diverse diseases states.« less

Towards terrain interaction prediction for bioinspired planetary exploration rovers.

PubMed

Yeomans, Brian; Saaj, Chakravathini M

2014-03-01

Deployment of a small legged vehicle to extend the reach of future planetary exploration missions is an attractive possibility but little is known about the behaviour of a walking rover on deformable planetary terrain. This paper applies ideas from the developing study of granular materials together with a detailed characterization of the sinkage process to propose and validate a combined model of terrain interaction based on an understanding of the physics and micro mechanics at the granular level. Whilst the model reflects the complexity of interactions expected from a walking rover, common themes emerge which enable the model to be streamlined to the extent that a simple mathematical representation is possible without resorting to numerical methods. Bespoke testing and analysis tools are described which reveal some unexpected conclusions and point the way towards intelligent control and foot geometry techniques to improve thrust generation.

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

Khrapak, Sergey A.; Joint Institute for High Temperatures, 125412 Moscow; Chaudhuri, Manis

We put forward an approximate method to locate the fluid-solid (freezing) phase transition in systems of classical particles interacting via a wide range of Lennard-Jones-type potentials. This method is based on the constancy of the properly normalized second derivative of the interaction potential (freezing indicator) along the freezing curve. As demonstrated recently it yields remarkably good agreement with previous numerical simulation studies of the conventional 12-6 Lennard-Jones (LJ) fluid [S.A.Khrapak, M.Chaudhuri, G.E.Morfill, Phys. Rev. B 134, 052101 (2010)]. In this paper, we test this approach using a wide range of the LJ-type potentials, including LJ n-6 and exp-6 models, andmore » find that it remains sufficiently accurate and reliable in reproducing the corresponding freezing curves, down to the triple-point temperatures. One of the possible application of the method--estimation of the freezing conditions in complex (dusty) plasmas with ''tunable'' interactions--is briefly discussed.« less

From the nonlinear Fokker-Planck equation to the Vlasov description and back: Confined interacting particles with drag

NASA Astrophysics Data System (ADS)

Plastino, A. R.; Curado, E. M. F.; Nobre, F. D.; Tsallis, C.

2018-02-01

Nonlinear Fokker-Planck equations endowed with power-law diffusion terms have proven to be valuable tools for the study of diverse complex systems in physics, biology, and other fields. The nonlinearity appearing in these evolution equations can be interpreted as providing an effective description of a system of particles interacting via short-range forces while performing overdamped motion under the effect of an external confining potential. This point of view has been recently applied to the study of thermodynamical features of interacting vortices in type II superconductors. In the present work we explore an embedding of the nonlinear Fokker-Planck equation within a Vlasov equation, thus incorporating inertial effects to the concomitant particle dynamics. Exact time-dependent solutions of the q -Gaussian form (with compact support) are obtained for the Vlasov equation in the case of quadratic confining potentials.

Green's functions for analysis of dynamic response of wheel/rail to vertical excitation

NASA Astrophysics Data System (ADS)

Mazilu, Traian

2007-09-01

An analytical model to simulate wheel/rail interaction using the Green's functions method is proposed in this paper. The model consists of a moving wheel on a discretely supported rail. Particularly for this model of rail, the bending and the longitudinal displacement are coupled due to the rail pad and a complex model of the rail pad is adopted. An efficient method for solving a time-domain analysis for wheel/rail interaction is presented. The method is based on the properties of the rail's Green functions and starting to these functions, a track's Green matrix is assembled for the numerical simulations of wheel/rail response due to three kinds of vertical excitations: the steady-state interaction, the rail corrugation and the wheel flat. The study points to influence of the worn rail—rigid contact—on variation in the wheel/rail contact force. The concept of pinned-pinned inhibitive rail pad is also presented.

The role of wine polysaccharides on salivary protein-tannin interaction: A molecular approach.

PubMed

Brandão, Elsa; Silva, Mafalda Santos; García-Estévez, Ignacio; Williams, Pascale; Mateus, Nuno; Doco, Thierry; de Freitas, Victor; Soares, Susana

2017-12-01

Polysaccharides are described to inhibit aggregation between food polyphenols and salivary proteins (SP) and may hence lead to astringency modulation. In this work, the effect of two wine polysaccharides (arabinogalactan proteins-AGPs and rhamnogalacturonan II- RGII) on SP-polyphenol interaction was evaluated. In general, both polysaccharides were effective to inhibit or reduce SP-polyphenol interaction and aggregation. They can act by two different mechanisms (ternary or competitive) depending on the SP-tannin pair. In the case of salivary P-B peptide, AGPs and RGII seem to act by a ternary mechanism, in which they surround this complex, enhancing its solubility. Concerning acidic proline-rich proteins (aPRPs), it was possible to observe both mechanisms, depending on the tannin and the polysaccharide involved. Overall, this work point out for a specific property of wine polysaccharides important to modulate this and other beverages and food astringency perception. Copyright © 2017 Elsevier Ltd. All rights reserved.

Frustration by design

DOE PAGES

Gilbert, Ian; Nisoli, Cristiano; Schiffer, Peter

2016-07-01

Geometrical frustration is a condition that occurs when a material’s lattice geometry precludes minimizing the energy of all the interactions among pairs of neighbors simultaneously. Moreover, the simplest example is three antiferromagnetically coupled Ising spins, pointing up or down, on the corners of an equilateral triangle: It is also impossible to arrange the spins so that each pair is antiparallel. In more complex magnetic lattices, the frustrated state can arise from the combination of lattice geometry and the strength and sign of the interactions among the magnetic dipole moments.1 (See the article by Roderich Moessner and Art Ramirez, Physics Today,more » February 2006, page 24.) A wide variety of exotic and collective phenomena sometimes arises from the competing interactions. One prime example is spin liquids, materials in which the local atomic moments fluctuate down to the lowest accessible temperatures and never settle into a static ground-state configuration.« less

Reproducible Bioconductor workflows using browser-based interactive notebooks and containers.

PubMed

Almugbel, Reem; Hung, Ling-Hong; Hu, Jiaming; Almutairy, Abeer; Ortogero, Nicole; Tamta, Yashaswi; Yeung, Ka Yee

2018-01-01

Bioinformatics publications typically include complex software workflows that are difficult to describe in a manuscript. We describe and demonstrate the use of interactive software notebooks to document and distribute bioinformatics research. We provide a user-friendly tool, BiocImageBuilder, that allows users to easily distribute their bioinformatics protocols through interactive notebooks uploaded to either a GitHub repository or a private server. We present four different interactive Jupyter notebooks using R and Bioconductor workflows to infer differential gene expression, analyze cross-platform datasets, process RNA-seq data and KinomeScan data. These interactive notebooks are available on GitHub. The analytical results can be viewed in a browser. Most importantly, the software contents can be executed and modified. This is accomplished using Binder, which runs the notebook inside software containers, thus avoiding the need to install any software and ensuring reproducibility. All the notebooks were produced using custom files generated by BiocImageBuilder. BiocImageBuilder facilitates the publication of workflows with a point-and-click user interface. We demonstrate that interactive notebooks can be used to disseminate a wide range of bioinformatics analyses. The use of software containers to mirror the original software environment ensures reproducibility of results. Parameters and code can be dynamically modified, allowing for robust verification of published results and encouraging rapid adoption of new methods. Given the increasing complexity of bioinformatics workflows, we anticipate that these interactive software notebooks will become as necessary for documenting software methods as traditional laboratory notebooks have been for documenting bench protocols, and as ubiquitous. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Inner-outer interactions in a turbulent boundary layer overlying complex roughness

NASA Astrophysics Data System (ADS)

Pathikonda, Gokul; Christensen, Kenneth T.

2017-04-01

Hot-wire measurements were performed in a zero-pressure-gradient turbulent boundary layer overlying both a smooth and a rough wall for the purpose of investigating the details of inner-outer flow interactions. The roughness considered embodies a broad range of topographical scales arranged in an irregular manner and reflects the topographical complexity often encountered in practical flow systems. Single-probe point-wise measurements with a traversing probe were made at two different regions of the rough-wall flow, which was previously shown to be heterogeneous in the spanwise direction, to investigate the distribution of streamwise turbulent kinetic energy and large scale-small scale interactions. In addition, two-probe simultaneous measurements were conducted enabling investigation of inner-outer interactions, wherein the large scales were independently sampled in the outer layer. Roughness-induced changes to the near-wall behavior were investigated, particularly by contrasting the amplitude and frequency modulation effects of inner-outer interactions in the rough-wall flow with well-established smooth-wall flow phenomena. It was observed that the rough-wall flow exhibits both amplitude and frequency modulation features close to the wall in a manner very similar to smooth-wall flow, though the correlated nature of these effects was found to be more intense in the rough-wall flow. In particular, frequency modulation was found to illuminate these enhanced modulation effects in the rough-wall flow. The two-probe measurements helped in evaluating the suitability of the interaction-schematic recently proposed by Baars et al., Exp. Fluids 56, 1 (2015), 10.1007/s00348-014-1876-4 for rough-wall flows. This model was found to be suitable for the rough-wall flow considered herein, and it was found that frequency modulation is a "cleaner" measure of the inner-outer modulation interactions for this rough-wall flow.

Structural Aspects for Evolution of [beta]-Lactamases from Penicillin-Binding Proteins

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

Meroueh, Samy O.; Minasov, George; Lee, Wenlin

Penicillin-binding proteins (PBPs), biosynthetic enzymes of bacterial cell wall assembly, and {beta}-lactamases, resistance enzymes to {beta}-lactam antibiotics, are related to each other from an evolutionary point of view. Massova and Mobashery (Antimicrob. Agents Chemother. 1998, 42, 1-17) have proposed that for {beta}-lactamases to have become effective at their function as antibiotic resistance enzymes, they would have had to undergo structure alterations such that they would not interact with the peptidoglycan, which is the substrate for PBPs. A cephalosporin analogue, 7{beta}-[N-Acetyl-L-alanyl-{gamma}-D-glutamyl-L-lysine]-3-acetoxymethyl-3-cephem-carboxylic acid (compound 6), was conceived and synthesized to test this notion. The X-ray structure of the complex of this cephalosporinmore » bound to the active site of the deacylation-deficient Q120L/Y150E variant of the class C AmpC {beta}-lactamase from Escherichia coli was solved at 1.71 {angstrom} resolution. This complex revealed that the surface for interaction with the strand of peptidoglycan that acylates the active site, which is present in PBPs, is absent in the {beta}-lactamase active site. Furthermore, insertion of a peptide in the {beta}-lactamase active site at a location where the second strand of peptidoglycan in some PBPs binds has effectively abolished the possibility for such interaction with the {beta}-lactamase. A 2.6 ns dynamics simulation was carried out for the complex, which revealed that the peptidoglycan surrogate (i.e., the active-site-bound ligand) undergoes substantial motion and is not stabilized for binding within the active site. These factors taken together disclose the set of structure modifications in the antibiotic resistance enzyme that prevent it from interacting with the peptidoglycan, en route to achieving catalytic proficiency for their intended function.« less

Membrane-localized extra-large G proteins and Gbg of the heterotrimeric G proteins form functional complexes engaged in plant immunity in Arabidopsis.

PubMed

Maruta, Natsumi; Trusov, Yuri; Brenya, Eric; Parekh, Urvi; Botella, José Ramón

2015-03-01

In animals, heterotrimeric G proteins, comprising Ga, Gb, and Gg subunits, are molecular switches whose function tightly depends on Ga and Gbg interaction. Intriguingly, in Arabidopsis (Arabidopsis thaliana), multiple defense responses involve Gbg, but not Ga. We report here that the Gbg dimer directly partners with extra-large G proteins (XLGs) to mediate plant immunity. Arabidopsis mutants deficient in XLGs, Gb, and Gg are similarly compromised in several pathogen defense responses, including disease development and production of reactive oxygen species. Genetic analysis of double, triple, and quadruple mutants confirmed that XLGs and Gbg functionally interact in the same defense signaling pathways. In addition, mutations in XLG2 suppressed the seedling lethal and cell death phenotypes of BRASSINOSTEROID INSENSITIVE1-associated receptor kinase1-interacting receptor-like kinase1 mutants in an identical way as reported for Arabidopsis Gb-deficient mutants. Yeast (Saccharomyces cerevisiae) three-hybrid and bimolecular fluorescent complementation assays revealed that XLG2 physically interacts with all three possible Gbg dimers at the plasma membrane. Phylogenetic analysis indicated a close relationship between XLGs and plant Ga subunits, placing the divergence point at the dawn of land plant evolution. Based on these findings, we conclude that XLGs form functional complexes with Gbg dimers, although the mechanism of action of these complexes, including activation/deactivation, must be radically different form the one used by the canonical Ga subunit and are not likely to share the same receptors. Accordingly, XLGs expand the repertoire of heterotrimeric G proteins in plants and reveal a higher level of diversity in heterotrimeric G protein signaling.

Biofilm infections between Scylla and Charybdis: interplay of host antimicrobial peptides and antibiotics

PubMed Central

Gordya, Natalia; Tulin, Dmitry; Yakovlev, Andrey

2018-01-01

Purpose The aim of this study is to improve the anti-biofilm activity of antibiotics. We hypothesized that the antimicrobial peptide (AMP) complex of the host’s immune system can be used for this purpose and examined the assumption on model biofilms. Methods FLIP7, the AMP complex of the blowfly Calliphora vicina containing a combination of defensins, cecropins, diptericins and proline-rich peptides was isolated from the hemolymph of bacteria-challenged maggots. The complex interaction with antibiotics of various classes was studied in biofilm and planktonic cultures of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii by the checkerboard method using trimethyl tetrazolium chloride cell viability and crystal violet biofilm eradication assays supplemented with microscopic analysis. Results We found that FLIP7 demonstrated: high synergy (fractional inhibitory concentration index <0.25) with meropenem, amikacin, kanamycin, ampicillin, vancomycin and cefotaxime; synergy with clindamycin, erythromycin and chloramphenicol; additive interaction with oxacillin, tetracycline, ciprofloxacin and gentamicin; and no interaction with polymyxin B. The interaction in planktonic cell models was significantly weaker than in biofilms of the same strains. The analysis of the dose–effect curves pointed to persister cells as a likely target of FLIP7 synergistic effect. The biofilm eradication assay showed that the effect also caused total destruction of S. aureus and E. coli biofilm materials. The effect allowed reducing the effective anti-biofilm concentration of the antibiotic to a level well below the one clinically achievable (2–3 orders of magnitude in the case of meropenem, ampicillin, cefotaxime and oxacillin). Conclusion FLIP7 is a highly efficient host antimicrobial system helping antibiotics to overcome biofilm barriers through persisters’ sensitization and biofilm material destruction. It is promising for the treatment of biofilm infections as an adjuvant of various small-molecule antibiotics. PMID:29674848

Untangling the Gordian knot of HIV, stress, and cognitive impairment.

PubMed

Valdez, Arielle N; Rubin, Leah H; Neigh, Gretchen N

2016-10-01

As individuals live longer with HIV, this "graying of the HIV epidemic" has introduced a new set of challenges including a growing number of age and inflammation-related diseases such as cardiovascular disease, type II diabetes, cancer, and dementia. The biological underpinnings of these complex and co-morbid diseases are not fully understood and become very difficult to disentangle in the context of HIV and aging. In the current review we examine the contributions and interactions of HIV, stress, and cognitive impairment and query the extent to which inflammation is the linchpin in these dynamic interactions. Given the inter-relatedness of stress, inflammatory mechanisms, HIV, and cognitive impairment, future work will either need to address multiple dimensions simultaneously or embrace the philosophy that breaking the aberrant cycle at any one point will subsequently remedy the other related systems and processes. Such a single-point intervention may be effective in early disease states, but after perpetuation of an aberrant cycle, adaptations in an attempt to internally resolve the issue will likely lead to the need for multifaceted interventions. Acknowledging that HIV, inflammation, and stress may interact with one another and collectively impact cognitive ability is an important step in fully understanding an individual's complete clinical picture and moving towards personalized medicine.

Seven lessons from manyfield inflation in random potentials

NASA Astrophysics Data System (ADS)

Dias, Mafalda; Frazer, Jonathan; Marsh, M. C. David

2018-01-01

We study inflation in models with many interacting fields subject to randomly generated scalar potentials. We use methods from non-equilibrium random matrix theory to construct the potentials and an adaption of the `transport method' to evolve the two-point correlators during inflation. This construction allows, for the first time, for an explicit study of models with up to 100 interacting fields supporting a period of `approximately saddle-point' inflation. We determine the statistical predictions for observables by generating over 30,000 models with 2–100 fields supporting at least 60 efolds of inflation. These studies lead us to seven lessons: i) Manyfield inflation is not single-field inflation, ii) The larger the number of fields, the simpler and sharper the predictions, iii) Planck compatibility is not rare, but future experiments may rule out this class of models, iv) The smoother the potentials, the sharper the predictions, v) Hyperparameters can transition from stiff to sloppy, vi) Despite tachyons, isocurvature can decay, vii) Eigenvalue repulsion drives the predictions. We conclude that many of the `generic predictions' of single-field inflation can be emergent features of complex inflation models.

Roles for SH2 and SH3 domains in Lyn kinase association with activated FcepsilonRI in RBL mast cells revealed by patterned surface analysis.

PubMed

Hammond, Stephanie; Wagenknecht-Wiesner, Alice; Veatch, Sarah L; Holowka, David; Baird, Barbara

2009-10-01

In mast cells, antigen-mediated cross-linking of IgE bound to its high-affinity surface receptor, FcepsilonRI, initiates a signaling cascade that culminates in degranulation and release of allergic mediators. Antigen-patterned surfaces, in which the antigen is deposited in micron-sized features on a silicon substrate, were used to examine the spatial relationship between clustered IgE-FcepsilonRI complexes and Lyn, the signal-initiating tyrosine kinase. RBL mast cells expressing wild-type Lyn-EGFP showed co-redistribution of this protein with clustered IgE receptors on antigen-patterned surfaces, whereas Lyn-EGFP containing an inhibitory point mutation in its SH2 domain did not significantly accumulate with the patterned antigen, and Lyn-EGFP with an inhibitory point mutation in its SH3 domain exhibited reduced interactions. Our results using antigen-patterned surfaces and quantitative cross-correlation image analysis reveal that both the SH2 and SH3 domains contribute to interactions between Lyn kinase and cross-linked IgE receptors in stimulated mast cells.

Evaluation of the exchange interaction and crystal fields in a prototype Dy2 SMM

NASA Astrophysics Data System (ADS)

Zhang, Qing; Sarachik, Myriam; Baker, Michael; Chen, Yizhang; Kent, Andrew; Pineda, Eufemio; McInnes, Eric

In order to gain an understanding of the INS and magnetization data obtained for Dy2, the simplest member of a newly synthesized family of dysprosium-based molecular magnets, we report on calculations of the magnetic behavior of a Dy2 cluster with the formula [hqH2][Dy2(hq)4(NO3)3].MeOH. The molecular complex contains one high symmetry Dy(III) ion and one low symmetry Dy(III) ion. Our calculations suggest that exchange coupling between the two ions controls the behavior of the magnetization at low temperature, while the crystal field of the low symmetry Dy(III) ion controls the behavior at higher temperature. A point charge electrostatic model, based on crystallographic coordinates, provides a starting point for the determination of the crystal field. Parameters in these calculations are adjusted to provide best fits to inelastic neutron scattering data (INS) and low temperature magnetometry: the INS measurements access crystal field energies and low temperature magnetization probes the Dy-Dy exchange interaction. Work supported by ARO W911NF-13-1-1025 (CCNY) and NSF-DMR-1309202 (NYU).

Storage Costs and Heuristics Interact to Produce Patterns of Aphasic Sentence Comprehension Performance

PubMed Central

Clark, David Glenn

2012-01-01

Background: Despite general agreement that aphasic individuals exhibit difficulty understanding complex sentences, the nature of sentence complexity itself is unresolved. In addition, aphasic individuals appear to make use of heuristic strategies for understanding sentences. This research is a comparison of predictions derived from two approaches to the quantification of sentence complexity, one based on the hierarchical structure of sentences, and the other based on dependency locality theory (DLT). Complexity metrics derived from these theories are evaluated under various assumptions of heuristic use. Method: A set of complexity metrics was derived from each general theory of sentence complexity and paired with assumptions of heuristic use. Probability spaces were generated that summarized the possible patterns of performance across 16 different sentence structures. The maximum likelihood of comprehension scores of 42 aphasic individuals was then computed for each probability space and the expected scores from the best-fitting points in the space were recorded for comparison to the actual scores. Predictions were then compared using measures of fit quality derived from linear mixed effects models. Results: All three of the metrics that provide the most consistently accurate predictions of patient scores rely on storage costs based on the DLT. Patients appear to employ an Agent–Theme heuristic, but vary in their tendency to accept heuristically generated interpretations. Furthermore, the ability to apply the heuristic may be degraded in proportion to aphasia severity. Conclusion: DLT-derived storage costs provide the best prediction of sentence comprehension patterns in aphasia. Because these costs are estimated by counting incomplete syntactic dependencies at each point in a sentence, this finding suggests that aphasia is associated with reduced availability of cognitive resources for maintaining these dependencies. PMID:22590462

Storage costs and heuristics interact to produce patterns of aphasic sentence comprehension performance.

PubMed

Clark, David Glenn

2012-01-01

Despite general agreement that aphasic individuals exhibit difficulty understanding complex sentences, the nature of sentence complexity itself is unresolved. In addition, aphasic individuals appear to make use of heuristic strategies for understanding sentences. This research is a comparison of predictions derived from two approaches to the quantification of sentence complexity, one based on the hierarchical structure of sentences, and the other based on dependency locality theory (DLT). Complexity metrics derived from these theories are evaluated under various assumptions of heuristic use. A set of complexity metrics was derived from each general theory of sentence complexity and paired with assumptions of heuristic use. Probability spaces were generated that summarized the possible patterns of performance across 16 different sentence structures. The maximum likelihood of comprehension scores of 42 aphasic individuals was then computed for each probability space and the expected scores from the best-fitting points in the space were recorded for comparison to the actual scores. Predictions were then compared using measures of fit quality derived from linear mixed effects models. All three of the metrics that provide the most consistently accurate predictions of patient scores rely on storage costs based on the DLT. Patients appear to employ an Agent-Theme heuristic, but vary in their tendency to accept heuristically generated interpretations. Furthermore, the ability to apply the heuristic may be degraded in proportion to aphasia severity. DLT-derived storage costs provide the best prediction of sentence comprehension patterns in aphasia. Because these costs are estimated by counting incomplete syntactic dependencies at each point in a sentence, this finding suggests that aphasia is associated with reduced availability of cognitive resources for maintaining these dependencies.

Electrophysiological and Kinematic Correlates of Communicative Intent in the Planning and Production of Pointing Gestures and Speech.

PubMed

Peeters, David; Chu, Mingyuan; Holler, Judith; Hagoort, Peter; Özyürek, Aslı

2015-12-01

In everyday human communication, we often express our communicative intentions by manually pointing out referents in the material world around us to an addressee, often in tight synchronization with referential speech. This study investigated whether and how the kinematic form of index finger pointing gestures is shaped by the gesturer's communicative intentions and how this is modulated by the presence of concurrently produced speech. Furthermore, we explored the neural mechanisms underpinning the planning of communicative pointing gestures and speech. Two experiments were carried out in which participants pointed at referents for an addressee while the informativeness of their gestures and speech was varied. Kinematic and electrophysiological data were recorded online. It was found that participants prolonged the duration of the stroke and poststroke hold phase of their gesture to be more communicative, in particular when the gesture was carrying the main informational burden in their multimodal utterance. Frontal and P300 effects in the ERPs suggested the importance of intentional and modality-independent attentional mechanisms during the planning phase of informative pointing gestures. These findings contribute to a better understanding of the complex interplay between action, attention, intention, and language in the production of pointing gestures, a communicative act core to human interaction.

Physical approach to complex systems

NASA Astrophysics Data System (ADS)

Kwapień, Jarosław; Drożdż, Stanisław

2012-06-01

Typically, complex systems are natural or social systems which consist of a large number of nonlinearly interacting elements. These systems are open, they interchange information or mass with environment and constantly modify their internal structure and patterns of activity in the process of self-organization. As a result, they are flexible and easily adapt to variable external conditions. However, the most striking property of such systems is the existence of emergent phenomena which cannot be simply derived or predicted solely from the knowledge of the systems’ structure and the interactions among their individual elements. This property points to the holistic approaches which require giving parallel descriptions of the same system on different levels of its organization. There is strong evidence-consolidated also in the present review-that different, even apparently disparate complex systems can have astonishingly similar characteristics both in their structure and in their behaviour. One can thus expect the existence of some common, universal laws that govern their properties. Physics methodology proves helpful in addressing many of the related issues. In this review, we advocate some of the computational methods which in our opinion are especially fruitful in extracting information on selected-but at the same time most representative-complex systems like human brain, financial markets and natural language, from the time series representing the observables associated with these systems. The properties we focus on comprise the collective effects and their coexistence with noise, long-range interactions, the interplay between determinism and flexibility in evolution, scale invariance, criticality, multifractality and hierarchical structure. The methods described either originate from “hard” physics-like the random matrix theory-and then were transmitted to other fields of science via the field of complex systems research, or they originated elsewhere but turned out to be very useful also in physics - like, for example, fractal geometry. Further methods discussed borrow from the formalism of complex networks, from the theory of critical phenomena and from nonextensive statistical mechanics. Each of these methods is helpful in analyses of specific aspects of complexity and all of them are mutually complementary.

Safety considerations in the pharmacological management of atrial fibrillation.

PubMed

Camm, A John

2008-07-21

The pharmacological management of atrial fibrillation (AF) requires careful consideration from a safety perspective. This article focuses primarily on maintenance therapy using antiarrhythmic drugs (AADs). The foremost safety issue for AADs is the propensity of class IA and III agents to cause torsade de pointes arrhythmias. Class IA drugs, particularly quinidine, can induce torsade de pointes at low or subtherapeutic doses, but higher doses are not necessarily associated with an increased incidence. 'Pure' class III drugs such as dofetilide induce torsade de pointes in a dose-related manner, but some class III agents with more complex actions such as amiodarone have a markedly lower potential to cause this arrhythmia. The risk of torsade de pointes precludes the use of class IA and 'pure' class III agents in patients with left ventricular hypertrophy and bradycardia. Class IC agents may cause sustained monomorphic ventricular tachycardias and are generally precluded in ischaemic and structural heart disease. Advanced heart failure patients may be treated with amiodarone or dofetilide, but most other AADs are unsuitable. The most important extracardiac toxicities occurring with AADs are those of amiodarone. Drug interactions are a significant safety issue in the management of AF, including pharmacokinetic interactions in which plasma levels of the AAD are raised - increasing the risk of proarrhythmia - and concomitant use of drugs that prolong the QT interval. Notwithstanding these considerations, most patients with AF can be considered for rhythm control, provided there is adequate pre-treatment assessment and protocols for initiation, dosing and monitoring are followed with care.

Molecular modeling and spectroscopic studies on the interaction of the chiral drug venlafaxine hydrochloride with bovine serum albumin

NASA Astrophysics Data System (ADS)

Shahabadi, Nahid; Hadidi, Saba

2014-03-01

This study was designed to examine the interaction of racemic antidepressant drug "S,R-venlafaxine hydrochloride (VEN)" with bovine serum albumin (BSA) under physiological conditions. The mechanism of interaction was studied by spectroscopic techniques combination with molecular modeling. Stern-Volmer analysis of fluorescence quenching data shows the presence of the static quenching mechanism. The thermodynamic parameters indicated that the hydrogen bonding and weak van der Waals interactions are the predominant intermolecular forces stabilizing the complex. The number of binding sites (n) was calculated. Through the site marker competitive experiment, VEN was confirmed to be located in subdomain IIIA of BSA. The binding distance (r = 4.93 nm) between the donor BSA and acceptor VEN was obtained according to Förster's non-radiative energy transfer theory. According to UV-vis spectra and CD data binding of VEN leaded to conformational changes of BSA. Molecular docking simulations of S and R-VEN revealed that both isomers have similar interaction and the same binding sites, from this point of view S and R isomers are equal.

Quantum Mechanics for Everybody: An autonomous MOOC on EdX for nonscientists

NASA Astrophysics Data System (ADS)

Freericks, James; Cutler, Dylan; Vieira-Barbosa, Lucas

2017-01-01

We have launched a MOOC for nonscientists that teaches quantum mechanics using the Feynman methodology as outlined in his QED book and in a similar book by Daniel Styer. Using a combination of videos, voice-over powerpoint animations, computer simulations and interactive tutorials, we teach the fundamentals of quantum mechanics employing a minimum of math (high school algebra, square roots, and a little trigonometry) but going into detail on a number of complex quantum ideas. We begin with the Stern-Gerlach experiment, including delayed choice and Bell's inequality variants. Then we focus on light developing the quantum theory for partial reflection and diffraction. At this point we demonstrate the complexity of quantum physics by showing how watched and unwatched two-slit experiments behave differently and how quantum particles interfere. The four week course ends with advanced topics in light where we cover the idea of an interaction free measurement, the quantum Zeno effect and indistinguishable particles via the Hong-Ou-Mandel experiment. We hope this MOOC will reach thousands of students interesting in learning quantum mechanics without any dumbing down or the need to learn complex math. It can also be used with undergraduates to help with conceptual understanding. Funded by the National Science Foundation under grants numbered PHY-1620555 and PHY-1314295 and by Georgetown University.

Exploring the Multi-Layered Affordances of Composing and Performing Interactive Music with Responsive Technologies

PubMed Central

Einarsson, Anna; Ziemke, Tom

2017-01-01

The question motivating the work presented here, starting from a view of music as embodied and situated activity, is how can we account for the complexity of interactive music performance situations. These are situations in which human performers interact with responsive technologies, such as sensor-driven technology or sound synthesis affected by analysis of the performed sound signal. This requires investigating in detail the underlying mechanisms, but also providing a more holistic approach that does not lose track of the complex whole constituted by the interactions and relationships of composers, performers, audience, technologies, etc. The concept of affordances has frequently been invoked in musical research, which has seen a “bodily turn” in recent years, similar to the development of the embodied cognition approach in the cognitive sciences. We therefore begin by broadly delineating its usage in the cognitive sciences in general, and in music research in particular. We argue that what is still missing in the discourse on musical affordances is an encompassing theoretical framework incorporating the sociocultural dimensions that are fundamental to the situatedness and embodiment of interactive music performance and composition. We further argue that the cultural affordances framework, proposed by Rietveld and Kiverstein (2014) and recently articulated further by Ramstead et al. (2016) in this journal, although not previously applied to music, constitutes a promising starting point. It captures and elucidates this complex web of relationships in terms of shared landscapes and individual fields of affordances. We illustrate this with examples foremost from the first author's artistic work as composer and performer of interactive music. This sheds new light on musical composition as a process of construction—and embodied mental simulation—of situations, guiding the performers' and audience's attention in shifting fields of affordances. More generally, we believe that the theoretical perspectives and concrete examples discussed in this paper help to elucidate how situations—and with them affordances—are dynamically constructed through the interactions of various mechanisms as people engage in embodied and situated activity. PMID:29033880

Virtual Sensors for Advanced Controllers in Rehabilitation Robotics.

PubMed

Mancisidor, Aitziber; Zubizarreta, Asier; Cabanes, Itziar; Portillo, Eva; Jung, Je Hyung

2018-03-05

In order to properly control rehabilitation robotic devices, the measurement of interaction force and motion between patient and robot is an essential part. Usually, however, this is a complex task that requires the use of accurate sensors which increase the cost and the complexity of the robotic device. In this work, we address the development of virtual sensors that can be used as an alternative of actual force and motion sensors for the Universal Haptic Pantograph (UHP) rehabilitation robot for upper limbs training. These virtual sensors estimate the force and motion at the contact point where the patient interacts with the robot using the mathematical model of the robotic device and measurement through low cost position sensors. To demonstrate the performance of the proposed virtual sensors, they have been implemented in an advanced position/force controller of the UHP rehabilitation robot and experimentally evaluated. The experimental results reveal that the controller based on the virtual sensors has similar performance to the one using direct measurement (less than 0.005 m and 1.5 N difference in mean error). Hence, the developed virtual sensors to estimate interaction force and motion can be adopted to replace actual precise but normally high-priced sensors which are fundamental components for advanced control of rehabilitation robotic devices.

Toward a quantitative approach to migrants integration

NASA Astrophysics Data System (ADS)

Barra, A.; Contucci, P.

2010-03-01

Migration phenomena and all the related issues, like integration of different social groups, are intrinsically complex problems since they strongly depend on several competitive mechanisms as economic factors, cultural differences and many others. By identifying a few essential assumptions, and using the statistical mechanics of complex systems, we propose a novel quantitative approach that provides a minimal theory for those phenomena. We show that the competitive interactions in decision making between a population of N host citizens and P immigrants, a bi-partite spin-glass, give rise to a social consciousness inside the host community in the sense of the associative memory of neural networks. The theory leads to a natural quantitative definition of migrant's "integration" inside the community. From the technical point of view this minimal picture assumes, as control parameters, only general notions like the strength of the random interactions, the ratio between the sizes of the two parties and the cultural influence. Few steps forward, toward more refined models, which include a digression on the kind of the felt experiences and some structure on the random interaction topology (as dilution to avoid the plain mean-field approach) and correlations of experiences felt between the two parties (biasing the distribution of the coupling) are discussed at the end, where we show the robustness of our approach.

Efficient electronic structure theory via hierarchical scale-adaptive coupled-cluster formalism: I. Theory and computational complexity analysis

NASA Astrophysics Data System (ADS)

Lyakh, Dmitry I.

2018-03-01

A novel reduced-scaling, general-order coupled-cluster approach is formulated by exploiting hierarchical representations of many-body tensors, combined with the recently suggested formalism of scale-adaptive tensor algebra. Inspired by the hierarchical techniques from the renormalisation group approach, H/H2-matrix algebra and fast multipole method, the computational scaling reduction in our formalism is achieved via coarsening of quantum many-body interactions at larger interaction scales, thus imposing a hierarchical structure on many-body tensors of coupled-cluster theory. In our approach, the interaction scale can be defined on any appropriate Euclidean domain (spatial domain, momentum-space domain, energy domain, etc.). We show that the hierarchically resolved many-body tensors can reduce the storage requirements to O(N), where N is the number of simulated quantum particles. Subsequently, we prove that any connected many-body diagram consisting of a finite number of arbitrary-order tensors, e.g. an arbitrary coupled-cluster diagram, can be evaluated in O(NlogN) floating-point operations. On top of that, we suggest an additional approximation to further reduce the computational complexity of higher order coupled-cluster equations, i.e. equations involving higher than double excitations, which otherwise would introduce a large prefactor into formal O(NlogN) scaling.

Interactions of the "piano-stool" [ruthenium(II)(η(6) -arene)(quinolone)Cl](+) complexes with water; DFT computational study.

PubMed

Zábojníková, Tereza; Cajzl, Radim; Kljun, Jakob; Chval, Zdeněk; Turel, Iztok; Burda, Jaroslav V

2016-07-15

Full optimizations of stationary points along the reaction coordinate for the hydration of several quinolone Ru(II) half-sandwich complexes were performed in water environment using the B3PW91/6-31+G(d)/PCM/UAKS method. The role of diffuse functions (especially on oxygen) was found crucial for correct geometries along the reaction coordinate. Single-point (SP) calculations were performed at the B3LYP/6-311++G(2df,2pd)/DPCM/saled-UAKS level. In the first part, two possible reaction mechanisms-associative and dissociative were compared. It was found that the dissociative mechanism of the hydration process is kinetically slightly preferred. Another important conclusion concerns the reaction channels. It was found that substitution of chloride ligand (abbreviated in the text as dechlorination reaction) represents energetically and kinetically the most feasible pathway. In the second part the same hydration reaction was explored for reactivity comparison of the Ru(II)-complexes with several derivatives of nalidixic acid: cinoxacin, ofloxacin, and (thio)nalidixic acid. The hydration process is about four orders of magnitude faster in a basic solution compared to neutral/acidic environment with cinoxacin and nalidixic acid as the most reactive complexes in the former and latter environments, respectively. The explored hydration reaction is in all cases endergonic; nevertheless the endergonicity is substantially lower (by ∼6 kcal/mol) in basic environment. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Quantum-chemical, NMR, FT IR, and ESI MS studies of complexes of colchicine with Zn(II).

PubMed

Jankowski, Wojciech; Kurek, Joanna; Barczyński, Piotr; Hoffmann, Marcin

2017-04-01

Colchicine is a tropolone alkaloid from Colchicinum autumnale. It shows antifibrotic, antimitotic, and anti-inflammatory activities, and is used to treat gout and Mediterranean fever. In this work, complexes of colchicine with zinc(II) nitrate were synthesized and investigated using DFT, 1 H and 13 C NMR, FT IR, and ESI MS. The counterpoise-corrected and uncorrected interaction energies of these complexes were calculated. We also calculated their 1 H, 13 C NMR, and IR spectra and compared them with the corresponding experimentally obtained data. According to the ESI MS mass spectra, colchicine forms stable complexes with zinc(II) nitrate that have various stoichiometries: 2:1, 1:1:1, and 2:1:1 with respect to colchichine, Zn(II), and nitrate ion. All of the complexes were investigated using the quantum theory of atoms in molecules (QTAIM). The calculated and the measured spectra showed differences before and after the complexation process. Calculated electron densities and bond critical points indicated the presence of bonds between the ligands and the central cation in the investigated complexes that satisfied the quantum theory of atoms in molecules. Graphical Abstract DFT, NMR, FT IR, ESI MS, QTAIM and puckering studies of complexes of colchicine with Zn(II).

Integrated Tools for Future Distributed Engine Control Technologies

NASA Technical Reports Server (NTRS)

Culley, Dennis; Thomas, Randy; Saus, Joseph

2013-01-01

Turbine engines are highly complex mechanical systems that are becoming increasingly dependent on control technologies to achieve system performance and safety metrics. However, the contribution of controls to these measurable system objectives is difficult to quantify due to a lack of tools capable of informing the decision makers. This shortcoming hinders technology insertion in the engine design process. NASA Glenn Research Center is developing a Hardware-inthe- Loop (HIL) platform and analysis tool set that will serve as a focal point for new control technologies, especially those related to the hardware development and integration of distributed engine control. The HIL platform is intended to enable rapid and detailed evaluation of new engine control applications, from conceptual design through hardware development, in order to quantify their impact on engine systems. This paper discusses the complex interactions of the control system, within the context of the larger engine system, and how new control technologies are changing that paradigm. The conceptual design of the new HIL platform is then described as a primary tool to address those interactions and how it will help feed the insertion of new technologies into future engine systems.

BeAtMuSiC: Prediction of changes in protein-protein binding affinity on mutations.

PubMed

Dehouck, Yves; Kwasigroch, Jean Marc; Rooman, Marianne; Gilis, Dimitri

2013-07-01

The ability of proteins to establish highly selective interactions with a variety of (macro)molecular partners is a crucial prerequisite to the realization of their biological functions. The availability of computational tools to evaluate the impact of mutations on protein-protein binding can therefore be valuable in a wide range of industrial and biomedical applications, and help rationalize the consequences of non-synonymous single-nucleotide polymorphisms. BeAtMuSiC (http://babylone.ulb.ac.be/beatmusic) is a coarse-grained predictor of the changes in binding free energy induced by point mutations. It relies on a set of statistical potentials derived from known protein structures, and combines the effect of the mutation on the strength of the interactions at the interface, and on the overall stability of the complex. The BeAtMuSiC server requires as input the structure of the protein-protein complex, and gives the possibility to assess rapidly all possible mutations in a protein chain or at the interface, with predictive performances that are in line with the best current methodologies.

Introduction: Microbiome in human reproduction.

PubMed

Franasiak, Jason M; Scott, Richard T

2015-12-01

The human microbiome has been termed the "second human genome" and data that has come about of late certainly makes it appear every bit as complex. The human body contains 10-fold more microbial cells than the human cells and accounts for 1%-3% of our total body mass. As we learn more about this symbiotic relationship, it appears this complex interaction occurs in nearly every part of the body, even those areas at one time considered to be sterile. Indeed, the microbiome in human reproduction has been investigated in terms of both the lower and upper reproductive tract and includes interactions even at the point of gametogenesis. What is all the more fascinating is that we have known about the importance of microbes for over 150 years, even before they existed in name. And now, with the assistance of an exciting technologic revolution which has pushed forward our understanding of the microbiome, we appear to stand on the precipice of a higher level of understanding of microbes, the biofilms they create, and their impact of health and disease in human reproduction. Copyright © 2015. Published by Elsevier Inc.

Sequential Monte Carlo Instant Radiosity.

PubMed

Hedman, Peter; Karras, Tero; Lehtinen, Jaakko

2017-05-01

Instant Radiosity and its derivatives are interactive methods for efficiently estimating global (indirect) illumination. They represent the last indirect bounce of illumination before the camera as the composite radiance field emitted by a set of virtual point light sources (VPLs). In complex scenes, current algorithms suffer from a difficult combination of two issues: it remains a challenge to distribute VPLs in a manner that simultaneously gives a high-quality indirect illumination solution for each frame, and to do so in a temporally coherent manner. We address both issues by building, and maintaining over time, an adaptive and temporally coherent distribution of VPLs in locations where they bring indirect light to the image. We introduce a novel heuristic sampling method that strives to only move as few of the VPLs between frames as possible. The result is, to the best of our knowledge, the first interactive global illumination algorithm that works in complex, highly-occluded scenes, suffers little from temporal flickering, supports moving cameras and light sources, and is output-sensitive in the sense that it places VPLs in locations that matter most to the final result.

Tudor domain containing 12 (TDRD12) is essential for secondary PIWI interacting RNA biogenesis in mice.

PubMed

Pandey, Radha Raman; Tokuzawa, Yoshimi; Yang, Zhaolin; Hayashi, Eri; Ichisaka, Tomoko; Kajita, Shimpei; Asano, Yuka; Kunieda, Tetsuo; Sachidanandam, Ravi; Chuma, Shinichiro; Yamanaka, Shinya; Pillai, Ramesh S

2013-10-08

Piwi-interacting RNAs (piRNAs) are gonad-specific small RNAs that provide defense against transposable genetic elements called transposons. Our knowledge of piRNA biogenesis is sketchy, partly due to an incomplete inventory of the factors involved. Here, we identify Tudor domain-containing 12 (TDRD12; also known as ECAT8) as a unique piRNA biogenesis factor in mice. TDRD12 is detected in complexes containing Piwi protein MILI (PIWIL2), its associated primary piRNAs, and TDRD1, all of which are already implicated in secondary piRNA biogenesis. Male mice carrying either a nonsense point mutation (reproductive mutant 23 or repro23 mice) or a targeted deletion in the Tdrd12 locus are infertile and derepress retrotransposons. We find that TDRD12 is dispensable for primary piRNA biogenesis but essential for production of secondary piRNAs that enter Piwi protein MIWI2 (PIWIL4). Cell-culture studies with the insect ortholog of TDRD12 suggest a role for the multidomain protein in mediating complex formation with other participants during secondary piRNA biogenesis.

The application of an MPM-MFM method for simulating weapon-target interaction.

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

Ma, X.; Zou, Q.; Zhang, D. Z.

2005-01-01

During the past two decades, Los Alamos National Laboratory (LANL) has developed computational algorithms and software for analysis of multiphase flow suitable for high-speed projectile penetration of metallic and nonmetallic materials, using a material point method (MPM)-multiphase flow method (MFM). Recently, ACTA has teamed with LANL to advance a computational algorithm for simulating complex weapon-target interaction for penetrating and exploding munitions, such as tank rounds and artillery shells, as well as non-exploding kinetic energy penetrators. This paper will outline the mathematical basis for the MPM-MFM method as implemented in LANL's CartaBlanca code. CartaBlanca, written entirely in Java using object-oriented design,more » is used to solve complex problems involving (a) failure and penetration of solids, (b) heat transfer, (c) phase change, (d) chemical reactions, and (e) multiphase flow. We will present its application to the penetration of a steel target by a tungsten cylinder and compare results with time-resolved experimental data published by Anderson, et. al., Int. J. Impact Engng., Vol. 16, No. 1, pp. 1-18, 1995.« less

Structure-Guided Design of Peptides as Tools to Probe the Protein-Protein Interaction between Cullin-2 and Elongin BC Substrate Adaptor in Cullin RING E3 Ubiquitin Ligases.

PubMed

Cardote, Teresa A F; Ciulli, Alessio

2017-09-21

Cullin RING E3 ubiquitin ligases (CRLs) are large dynamic multi-subunit complexes that control the fate of many proteins in cells. CRLs are attractive drug targets for the development of small-molecule inhibitors and chemical inducers of protein degradation. Herein we describe a structure-guided biophysical approach to probe the protein-protein interaction (PPI) between the Cullin-2 scaffold protein and the adaptor subunits Elongin BC within the context of the von Hippel-Lindau complex (CRL2 VHL ) using peptides. Two peptides were shown to bind at the targeted binding site on Elongin C, named the "EloC site", with micromolar dissociation constants, providing a starting point for future optimization. Our results suggest ligandability of the EloC binding site to short linear peptides, unveiling the opportunity and challenges to develop small molecules that have the potential to target selectively the Cul2-adaptor PPI within CRLs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Novel Mammalian Complex Containing Sin3B Mitigates Histone Acetylation and RNA Polymerase II Progression within Transcribed Loci▿

PubMed Central

Jelinic, Petar; Pellegrino, Jessica; David, Gregory

2011-01-01

Transcription requires the progression of RNA polymerase II (RNAP II) through a permissive chromatin structure. Recent studies of Saccharomyces cerevisiae have demonstrated that the yeast Sin3 protein contributes to the restoration of the repressed chromatin structure at actively transcribed loci. Yet, the mechanisms underlying the restoration of the repressive chromatin structure at transcribed loci and its significance in gene expression have not been investigated in mammals. We report here the identification of a mammalian complex containing the corepressor Sin3B, the histone deacetylase HDAC1, Mrg15, and the PHD finger-containing Pf1 and show that this complex plays important roles in regulation of transcription. We demonstrate that this complex localizes at discrete loci approximately 1 kb downstream of the transcription start site of transcribed genes, and this localization requires both Pf1's and Mrg15's interaction with chromatin. Inactivation of this mammalian complex promotes increased RNAP II progression within transcribed regions and subsequent increased transcription. Our results define a novel mammalian complex that contributes to the regulation of transcription and point to divergent uses of the Sin3 protein homologues throughout evolution in the modulation of transcription. PMID:21041482

Semantics of directly manipulating spatializations.

PubMed

Hu, Xinran; Bradel, Lauren; Maiti, Dipayan; House, Leanna; North, Chris; Leman, Scotland

2013-12-01

When high-dimensional data is visualized in a 2D plane by using parametric projection algorithms, users may wish to manipulate the layout of the data points to better reflect their domain knowledge or to explore alternative structures. However, few users are well-versed in the algorithms behind the visualizations, making parameter tweaking more of a guessing game than a series of decisive interactions. Translating user interactions into algorithmic input is a key component of Visual to Parametric Interaction (V2PI) [13]. Instead of adjusting parameters, users directly move data points on the screen, which then updates the underlying statistical model. However, we have found that some data points that are not moved by the user are just as important in the interactions as the data points that are moved. Users frequently move some data points with respect to some other 'unmoved' data points that they consider as spatially contextual. However, in current V2PI interactions, these points are not explicitly identified when directly manipulating the moved points. We design a richer set of interactions that makes this context more explicit, and a new algorithm and sophisticated weighting scheme that incorporates the importance of these unmoved data points into V2PI.

Corresponding-states behavior of an ionic model fluid with variable dispersion interactions

NASA Astrophysics Data System (ADS)

Weiss, Volker C.

2016-06-01

Guggenheim's corresponding-states approach for simple fluids leads to a remarkably universal representation of their thermophysical properties. For more complex fluids, such as polar or ionic ones, deviations from this type of behavior are to be expected, thereby supplying us with valuable information about the thermodynamic consequences of the interaction details in fluids. Here, the gradual transition of a simple fluid to an ionic one is studied by varying the relative strength of the dispersion interactions compared to the electrostatic interactions among the charged particles. In addition to the effects on the reduced surface tension that were reported earlier [F. Leroy and V. C. Weiss, J. Chem. Phys. 134, 094703 (2011)], we address the shape of the coexistence curve and focus on properties that are related to and derived from the vapor pressure. These quantities include the enthalpy and entropy of vaporization, the boiling point, and the critical compressibility factor Zc. For all of these properties, the crossover from simple to characteristically ionic fluid is seen once the dispersive attraction drops below 20%-40% of the electrostatic attraction (as measured for two particles at contact). Below this threshold, ionic fluids display characteristically low values of Zc as well as large Guggenheim and Guldberg ratios for the reduced enthalpy of vaporization and the reduced boiling point, respectively. The coexistence curves are wider and more skewed than those for simple fluids. The results for the ionic model fluid with variable dispersion interactions improve our understanding of the behavior of real ionic fluids, such as inorganic molten salts and room temperature ionic liquids, by gauging the importance of different types of interactions for thermodynamic properties.

Functional Logistic Regression Approach to Detecting Gene by Longitudinal Environmental Exposure Interaction in a Case-Control Study

PubMed Central

Wei, Peng; Tang, Hongwei; Li, Donghui

2014-01-01

Most complex human diseases are likely the consequence of the joint actions of genetic and environmental factors. Identification of gene-environment (GxE) interactions not only contributes to a better understanding of the disease mechanisms, but also improves disease risk prediction and targeted intervention. In contrast to the large number of genetic susceptibility loci discovered by genome-wide association studies, there have been very few successes in identifying GxE interactions which may be partly due to limited statistical power and inaccurately measured exposures. While existing statistical methods only consider interactions between genes and static environmental exposures, many environmental/lifestyle factors, such as air pollution and diet, change over time, and cannot be accurately captured at one measurement time point or by simply categorizing into static exposure categories. There is a dearth of statistical methods for detecting gene by time-varying environmental exposure interactions. Here we propose a powerful functional logistic regression (FLR) approach to model the time-varying effect of longitudinal environmental exposure and its interaction with genetic factors on disease risk. Capitalizing on the powerful functional data analysis framework, our proposed FLR model is capable of accommodating longitudinal exposures measured at irregular time points and contaminated by measurement errors, commonly encountered in observational studies. We use extensive simulations to show that the proposed method can control the Type I error and is more powerful than alternative ad hoc methods. We demonstrate the utility of this new method using data from a case-control study of pancreatic cancer to identify the windows of vulnerability of lifetime body mass index on the risk of pancreatic cancer as well as genes which may modify this association. PMID:25219575

Functional logistic regression approach to detecting gene by longitudinal environmental exposure interaction in a case-control study.

PubMed

Wei, Peng; Tang, Hongwei; Li, Donghui

2014-11-01

Most complex human diseases are likely the consequence of the joint actions of genetic and environmental factors. Identification of gene-environment (G × E) interactions not only contributes to a better understanding of the disease mechanisms, but also improves disease risk prediction and targeted intervention. In contrast to the large number of genetic susceptibility loci discovered by genome-wide association studies, there have been very few successes in identifying G × E interactions, which may be partly due to limited statistical power and inaccurately measured exposures. Although existing statistical methods only consider interactions between genes and static environmental exposures, many environmental/lifestyle factors, such as air pollution and diet, change over time, and cannot be accurately captured at one measurement time point or by simply categorizing into static exposure categories. There is a dearth of statistical methods for detecting gene by time-varying environmental exposure interactions. Here, we propose a powerful functional logistic regression (FLR) approach to model the time-varying effect of longitudinal environmental exposure and its interaction with genetic factors on disease risk. Capitalizing on the powerful functional data analysis framework, our proposed FLR model is capable of accommodating longitudinal exposures measured at irregular time points and contaminated by measurement errors, commonly encountered in observational studies. We use extensive simulations to show that the proposed method can control the Type I error and is more powerful than alternative ad hoc methods. We demonstrate the utility of this new method using data from a case-control study of pancreatic cancer to identify the windows of vulnerability of lifetime body mass index on the risk of pancreatic cancer as well as genes that may modify this association. © 2014 Wiley Periodicals, Inc.

Corresponding-states behavior of an ionic model fluid with variable dispersion interactions

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

Weiss, Volker C., E-mail: volker.weiss@bccms.uni-bremen.de

2016-06-21

Guggenheim’s corresponding-states approach for simple fluids leads to a remarkably universal representation of their thermophysical properties. For more complex fluids, such as polar or ionic ones, deviations from this type of behavior are to be expected, thereby supplying us with valuable information about the thermodynamic consequences of the interaction details in fluids. Here, the gradual transition of a simple fluid to an ionic one is studied by varying the relative strength of the dispersion interactions compared to the electrostatic interactions among the charged particles. In addition to the effects on the reduced surface tension that were reported earlier [F. Leroymore » and V. C. Weiss, J. Chem. Phys. 134, 094703 (2011)], we address the shape of the coexistence curve and focus on properties that are related to and derived from the vapor pressure. These quantities include the enthalpy and entropy of vaporization, the boiling point, and the critical compressibility factor Z{sub c}. For all of these properties, the crossover from simple to characteristically ionic fluid is seen once the dispersive attraction drops below 20%–40% of the electrostatic attraction (as measured for two particles at contact). Below this threshold, ionic fluids display characteristically low values of Z{sub c} as well as large Guggenheim and Guldberg ratios for the reduced enthalpy of vaporization and the reduced boiling point, respectively. The coexistence curves are wider and more skewed than those for simple fluids. The results for the ionic model fluid with variable dispersion interactions improve our understanding of the behavior of real ionic fluids, such as inorganic molten salts and room temperature ionic liquids, by gauging the importance of different types of interactions for thermodynamic properties.« less

When high pressure, system constraints, and a social justice mission collide: A socio-structural analysis of emergency department social work services.

PubMed

Moore, Megan; Cristofalo, Margaret; Dotolo, Danae; Torres, Nicole; Lahdya, Alexandra; Ho, Leyna; Vogel, Mia; Forrester, Mollie; Conley, Bonnie; Fouts, Susan

2017-04-01

The emergency department (ED) can be a critical intervention point for many patients with multifaceted needs. Social workers have long been part of interdisciplinary ED teams. This study aimed to contribute to the limited understanding of social worker-patient interactions and factors influencing social work services in this setting. This paper reports a qualitative content analysis of social work medical record notes (N = 1509) of services provided to trauma patients in an urban, public, level 1 trauma center and an in-depth analysis of semi-structured interviews with ED social workers (N = 10). Eight major social work roles were identified: investigator, gatekeeper, resource broker, care coordinator, problem solver, crisis manager, advocate, discharge planner. Analyses revealed a complex interplay between ED social work services and multi-layered contexts. Using a social-ecological framework, we identified the interactions between micro or individual level factors, mezzo or local system level factors and macro environmental and systemic factors that play a role in ED interactions and patient services. Macro-level contextual influences were socio-structural forces including socioeconomic barriers to health, social hierarchies that reflected power differentials between providers and patients, and distrust or bias. Mezzo-level forces were limited resources, lack of healthcare system coordination, a challenging hierarchy within the medical model and the pressure to discharge patients quickly. Micro-level factors included characteristics of patients and social workers, complexity of patient stressors, empathic strain, lack of closure and compassion. All of these forces were at play in patient-social worker interactions and impacted service provision. Social workers were at times able to successfully navigate these forces, yet at other times these challenges were insurmountable. A conceptual model of ED social work and the influences on the patient-social worker interactions was developed to assist in guiding innovative research and practice models to improve services and outcomes in the complex, fast-paced ED. Copyright © 2017 Elsevier Ltd. All rights reserved.

When high pressure, system constraints, and a social justice mission collide: a socio-structural analysis of emergency department social work services

PubMed Central

Cristofalo, Margaret; Dotolo, Danae; Torres, Nicole; Lahdya, Alexandra; Ho, Leyna; Vogel, Mia; Forrester, Mollie; Conley, Bonnie; Fouts, Susan

2017-01-01

The emergency department (ED) can be a critical intervention point for many patients with multifaceted needs. Social workers have long been part of interdisciplinary ED teams. This study aimed to contribute to the limited understanding of social worker-patient interactions and factors influencing social work services in this setting. This paper reports a qualitative content analysis of social work medical record notes (N=1,509) of services provided to trauma patients in an urban, public, level 1 trauma center and an in-depth analysis of semi-structured interviews with ED social workers (N=10). Eight major social work roles were identified: investigator, gatekeeper, resource broker, care coordinator, problem solver, crisis manager, advocate, discharge planner. Analyses revealed a complex interplay between ED social work services and multi-layered contexts. Using a social-ecological framework, we identified the interactions between micro or individual level factors, mezzo or local system level factors and macro environmental and systemic factors that play a role in ED interactions and patient services. Macro-level contextual influences were socio-structural forces including socioeconomic barriers to health, social hierarchies that reflected power differentials between providers and patients, and distrust or bias. Mezzo-level forces were limited resources, lack of healthcare system coordination, a challenging hierarchy within the medical model and the pressure to discharge patients quickly. Micro-level factors included characteristics of patients and social workers, complexity of patient stressors, empathic strain, lack of closure and compassion. All of these forces were at play in patient-social worker interactions and impacted service provision. Social workers were at times able to successfully navigate these forces, yet at other times these challenges were insurmountable. A conceptual model of ED social work and the influences on the patient-social worker interactions was developed to assist in guiding innovative research and practice models to improve services and outcomes in the complex, fast-paced ED. PMID:28214722

The nature of cumulative impacts on biotic diversity of wetland vertebrates

NASA Astrophysics Data System (ADS)

Harris, Larry D.

1988-09-01

There is no longer any doubt that cumulative impacts have important effects on wetland vertebrates. Interactions of species diversity and community structure produce a complex pattern in which environmental impacts can play a highly significant role. Various examples show how wetlands maintain the biotic diversity within and among vertebrate populations, and some of the ways that environmental perturbations can interact to reduce this diversity. The trophic and habitat pyramids are useful organizing concepts. Habitat fragmentation can have severe effects at all levels, reducing the usable range of the larger habitat generalists while threatening the genetic integrity of small, isolated populations. The complexity of trophic interactions, and the propensity, or necessity, of vertebrates to switch from one food source to another—something we know little about—makes using food chain support as a variable for predicting environmental impacts very questionable. Historical instances illustrate the effects of the accumulation of impacts on vertebrates. At present it is nearly impossible to predict the result of three or more different kinds of perturbations, although long-range effects can be observed. One case in point is waterfowl; while their ingestion of lead shot, harvesting by hunters during migration, and loss of habitat have caused waterfowl populations to decline, the proportional responsibility of these factors has not been determined. Further examples show multiplicative effects of similar actions, effects with long time lags, diffuse processes in the landscape that may have concentrated effects on a component subsystem, and a variety of other interactions of increasing complexity. Not only is more information needed at all levels; impacts must be assessed on a landscape or regional scale to produce informed management decisions. I conclude that a system of replicate wetland reserves that are allowed to interact naturally with the surrounding landscape will be more effective in preserving biotic diversity than isolated sanctuaries.

The fanconi anemia proteins FANCA and FANCG stabilize each other and promote the nuclear accumulation of the Fanconi anemia complex.

PubMed

Garcia-Higuera, I; Kuang, Y; Denham, J; D'Andrea, A D

2000-11-01

Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with 8 complementation groups. Four of the FA genes have been cloned, and at least 3 of the encoded proteins, FANCA, FANCC, and FANCG/XRCC9, interact in a multisubunit protein complex. The FANCG protein binds directly to the amino terminal nuclear localization sequence (NLS) of FANCA, suggesting that FANCG plays a role in regulating FANCA nuclear accumulation. In the current study the functional consequences of FANCG/FANCA binding were examined. Correction of an FA-G cell line with the FANCG complementary DNA (cDNA) resulted in FANCA/FANCG binding, prolongation of the cellular half-life of FANCA, and an increase in the nuclear accumulation of the FA protein complex. Similar results were obtained upon correction of an FA-A cell line, with a reciprocal increase in the half-life of FANCG. Patient-derived mutant forms of FANCA, containing an intact NLS sequence but point mutations in the carboxy-terminal leucine zipper region, bound FANCG in the cytoplasm. The mutant forms failed to translocate to the nucleus of transduced cells, thereby suggesting a model of coordinated binding and nuclear translocation. These results demonstrate that the FANCA/FANCG interaction is required to maintain the cellular levels of both proteins. Moreover, at least one function of FANCG and FANCA is to regulate the nuclear accumulation of the FA protein complex. Failure to accumulate the nuclear FA protein complex results in the characteristic spectrum of clinical and cellular abnormalities observed in FA.

Impairment of autophagosome-lysosome fusion in the buff mutant mice with the VPS33AD251E mutation

PubMed Central

Zhen, Yuanli; Li, Wei

2015-01-01

The HOPS (homotypic fusion and protein sorting) complex functions in endocytic and autophagic pathways in both lower eukaryotes and mammalian cells through its involvement in fusion events between endosomes and lysosomes or autophagosomes and lysosomes. However, the differential molecular mechanisms underlying these fusion processes are largely unknown. Buff (bf) is a mouse mutant that carries an Asp251-to-Glu point mutation (D251E) in the VPS33A protein, a tethering protein and a core subunit of the HOPS complex. Bf mice showed impaired spontaneous locomotor activity, motor learning, and autophagic activity. Although the gross anatomy of the brain was apparently normal, the number of Purkinje cells was significantly reduced. Furthermore, we found that fusion between autophagosomes and lysosomes was defective in bf cells without compromising the endocytic pathway. The direct association of mutant VPS33AD251E with the autophagic SNARE complex, STX17 (syntaxin 17)-VAMP8-SNAP29, was enhanced. In addition, the VPS33AD251E mutation enhanced interactions with other HOPS subunits, namely VPS41, VPS39, VPS18, and VPS11, except for VPS16. Reduction of the interactions between VPS33AY440D and several other HOPS subunits led to decreased association with STX17. These results suggest that the VPS33AD251E mutation plays dual roles by increasing the HOPS complex assembly and its association with the autophagic SNARE complex, which selectively affects the autophagosome-lysosome fusion that impairs basal autophagic activity and induces Purkinje cell loss. PMID:26259518

Probing the modulated formation of gold nanoparticles-beta-lactoglobulin corona complexes and their applications.

PubMed

Yang, Jiang; Wang, Bo; You, Youngsang; Chang, Woo-Jin; Tang, Ke; Wang, Yi-Cheng; Zhang, Wenzhao; Ding, Feng; Gunasekaran, Sundaram

2017-11-23

Understanding the interactions between proteins and nanoparticles (NPs) along with the underlying structural and dynamic information is of utmost importance to exploit nanotechnology for biomedical applications. Upon adsorption onto a NP surface, proteins form a well-organized layer, termed the corona, that dictates the identity of the NP-protein complex and governs its biological pathways. Given its high biological relevance, in-depth molecular investigations and applications of NPs-protein corona complexes are still scarce, especially since different proteins form unique corona patterns, making identification of the biomolecular motifs at the interface critical. In this work, we provide molecular insights and structural characterizations of the bio-nano interface of a popular food-based protein, namely bovine beta-lactoglobulin (β-LG), with gold nanoparticles (AuNPs) and report on our investigations of the formation of corona complexes by combined molecular simulations and complementary experiments. Two major binding sites in β-LG were identified as being driven by citrate-mediated electrostatic interactions, while the associated binding kinetics and conformational changes in the secondary structures were also characterized. More importantly, the superior stability of the corona led us to further explore its biomedical applications, such as in the smartphone-based point-of-care biosensing of Escherichia coli (E. coli) and in the computed tomography (CT) of the gastrointestinal (GI) tract through oral administration to probe GI tolerance and functions. Considering their biocompatibility, edible nature, and efficient excretion through defecation, AuNPs-β-LG corona complexes have shown promising perspectives for future in vitro and in vivo clinical settings.

Formation of core-shell structured complex microparticles during fabrication of magnetorheological elastomers and their magnetorheological behavior

NASA Astrophysics Data System (ADS)

Wang, Yonghong; Zhang, Xinru; Chung, Kyungho; Liu, Chengcen; Choi, Seung-Bok; Choi, Hyoung Jin

2016-11-01

To improve mechanical and magnetorheological properties of magnetorheological elastomers (MREs), a facile method was used to fabricate high-performance MREs which consisted of the core-shell complex microparticles with an organic-inorganic network structure dispersed in an ethylene propylene diene rubber. In this work, the proposed magnetic complex microparticles were in situ formed during MREs fabrication as a result of strong interaction between matrix and CIPs using carbon black as a connecting point. The morphology of both isotropic (i-MREs) and anisotropic MREs (a-MREs) was observed by scanning electron microscope (SEM). The effects of carbonyl iron particle (CIP) volume content on mechanical properties and hysteresis loss of MREs were investigated. The effects of CIP volume content on the shear storage modulus, MR effect and loss tangent were studied using a modified dynamic mechanical analyzer under applied magnetic field strengths. The results showed that the orientation effect became more pronounced with increasing CIPs in the a-MREs, whereas CIPs distributed uniformly in the i-MREs. The tensile strength, tear strength and elongation at break decreased with increasing CIP content up to 40 vol.%, while the hardness increased. It is worth noting that the tensile strength of i-MREs and a-MREs containing 40 vol.% CIPs still had high mechanical properties as a result of good compatibility between complex microparticles and rubber matrix. The MR performance of shear storage modulus and damping properties of MREs increased remarkably with CIP content due to strong dipole-dipole interaction of complex microparticles. Besides, the hysteresis loss increased with increasing CIP content as a result of magnetic field induced interfacial sliding between complex microparticles.

Thermodynamic studies of drug-alpha-cyclodextrin interactions in water at 298.15 K: promazine hydrochloride/chlorpromazine hydrochloride + alpha-cyclodextrin + H(2)O systems.

PubMed

Terdale, Santosh S; Dagade, Dilip H; Patil, Kesharsingh J

2007-12-06

Data on osmotic coefficients have been obtained for a binary aqueous solution of two drugs, namely, promazine hydrochloride (PZ) and chlorpromazine hydrochloride (CPZ) using a vapor pressure osmometer at 298.15 K. The observed critical micelle concentration (cmc) agrees excellently with the available literature data. The measurements are extended to aqueous ternary solutions containing fixed a concentration of alpha-cyclodextrin (alpha-CD) of 0.1 mol kg(-1) and varied concentrations (approximately 0.005-0.2 mol kg(-1)) of drugs at 298.15 K. It has been found that the cmc values increase by the addition of alpha-CD. The mean molal activity coefficients of the ions and the activity coefficient of alpha-CD in binary as well as ternary solutions were obtained, which have been further used to calculate the excess Gibbs free energies and transfer Gibbs free energies. The lowering of the activity coefficients of ions and of alpha-CD is attributed to the existence of host-guest (inclusion)-type complex equilibria. It is suggested that CPZ forms 2:1 and 1:1 complexed species with alpha-CD, while PZ forms only 1:1 complexed species. The salting constant (ks) values are determined at 298.15 K for promazine-alpha-CD and chlorpromazine-alpha-CD complexes, respectively, by following the method based on the application of the McMillan-Mayer theory of virial coefficients to transfer free energy data. It is noted that the presence of chlorine in the drug molecule imparts better complexing capacity, the effect of which gets attenuated as a result of hydrophobic interaction. The results are discussed from the point of view of associative equilibria before the cmc and complexed equilibria for binary and ternary solutions, respectively.

Development of concepts on the interaction of drugs with opioid receptors

NASA Astrophysics Data System (ADS)

Kuzmina, N. E.; Kuzmin, V. S.

2011-02-01

The development of concepts on the molecular mechanisms of the action of medicinal drugs on the opioid receptors is briefly surveyed. The modern point of view on the mechanism of activation of opioid receptors is given based on the data from chimeric and site-directed mutagenesis of the cloned opioid receptors and the computer-aided simulations of the reception zone and ligand-receptor complexes. Three-dimensional models of the opioid pharmacophore derived by both conventional methods and a comparative analysis of molecular fields are described in detail.

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

Gilbert, Jack A.; Quinn, Robert A.; Debelius, Justine

Rapid advances in DNA sequencing, metabolomics, proteomics and computation dramatically increase accessibility of microbiome studies and identify links between the microbiome and disease. Microbial time-series and multiple molecular perspectives enable Microbiome-Wide Association Studies (MWAS), analogous to Genome-Wide Association Studies (GWAS). Rapid research advances point towards actionable results, although approved clinical tests based on MWAS are still in the future. Appreciating the complexity of interactions between diet, chemistry, health and the microbiome, and determining the frequency of observations needed to capture and integrate this dynamic interface, is paramount for addressing the need for personalized and precision microbiome-based diagnostics and therapies.

The quest for solvable multistate Landau-Zener models

DOE PAGES

Sinitsyn, Nikolai A.; Chernyak, Vladimir Y.

2017-05-24

Recently, integrability conditions (ICs) in mutistate Landau-Zener (MLZ) theory were proposed. They describe common properties of all known solved systems with linearly time-dependent Hamiltonians. Here we show that ICs enable efficient computer assisted search for new solvable MLZ models that span complexity range from several interacting states to mesoscopic systems with many-body dynamics and combinatorially large phase space. This diversity suggests that nontrivial solvable MLZ models are numerous. Additionally, we refine the formulation of ICs and extend the class of solvable systems to models with points of multiple diabatic level crossing.

Multidimensional extended spatial evolutionary games.

PubMed

Krześlak, Michał; Świerniak, Andrzej

2016-02-01

The goal of this paper is to study the classical hawk-dove model using mixed spatial evolutionary games (MSEG). In these games, played on a lattice, an additional spatial layer is introduced for dependence on more complex parameters and simulation of changes in the environment. Furthermore, diverse polymorphic equilibrium points dependent on cell reproduction, model parameters, and their simulation are discussed. Our analysis demonstrates the sensitivity properties of MSEGs and possibilities for further development. We discuss applications of MSEGs, particularly algorithms for modelling cell interactions during the development of tumours. Copyright © 2015 Elsevier Ltd. All rights reserved.

Study of Te Inclusion and Related Point Defects in THM-Growth CdMnTe Crystal

NASA Astrophysics Data System (ADS)

Mao, Yifei; Zhang, Jijun; Min, Jiahua; Liang, Xiaoyan; Huang, Jian; Tang, Ke; Ling, Liwen; Li, Ming; Zhang, Ying; Wang, Linjun

2018-02-01

This study establishes a model for describing the interaction between Te inclusions, dislocations and point defects in CdMnTe crystals. The role of the complex environment surrounding the formation of Te inclusions was analyzed. Images of Te inclusions captured by scanning electron microscope and infrared microscope were used to observe the morphology of Te inclusions. The morphology of Te inclusions is discussed in light of crystallography, from the crystal growth temperature at 900°C to the melting temperature of Te inclusions using the traveling heater method. The dislocation nets around Te inclusions were calculated by counting lattice mismatches between the Te inclusions and the bulk CdMnTe at 470°C. The point defects of Te antisites were found to be gathered around Te inclusions, with dislocation climb during the cooling phase of crystal growth from 470°C to room temperature. The Te inclusions, dislocation nets and surrounding point defects are considered to be an entirety for evaluating the effect of Te inclusions on CdMnTe detector performance, and an effective mobility-lifetime product (μτ) was obtained.

plas.io: Open Source, Browser-based WebGL Point Cloud Visualization

NASA Astrophysics Data System (ADS)

Butler, H.; Finnegan, D. C.; Gadomski, P. J.; Verma, U. K.

2014-12-01

Point cloud data, in the form of Light Detection and Ranging (LiDAR), RADAR, or semi-global matching (SGM) image processing, are rapidly becoming a foundational data type to quantify and characterize geospatial processes. Visualization of these data, due to overall volume and irregular arrangement, is often difficult. Technological advancement in web browsers, in the form of WebGL and HTML5, have made interactivity and visualization capabilities ubiquitously available which once only existed in desktop software. plas.io is an open source JavaScript application that provides point cloud visualization, exploitation, and compression features in a web-browser platform, reducing the reliance for client-based desktop applications. The wide reach of WebGL and browser-based technologies mean plas.io's capabilities can be delivered to a diverse list of devices -- from phones and tablets to high-end workstations -- with very little custom software development. These properties make plas.io an ideal open platform for researchers and software developers to communicate visualizations of complex and rich point cloud data to devices to which everyone has easy access.

Research activities at the Center for Modeling of Turbulence and Transition

NASA Technical Reports Server (NTRS)

Shih, Tsan-Hsing

1993-01-01

The main research activities at the Center for Modeling of Turbulence and Transition (CMOTT) are described. The research objective of CMOTT is to improve and/or develop turbulence and transition models for propulsion systems. The flows of interest in propulsion systems can be both compressible and incompressible, three dimensional, bounded by complex wall geometries, chemically reacting, and involve 'bypass' transition. The most relevant turbulence and transition models for the above flows are one- and two-equation eddy viscosity models, Reynolds stress algebraic- and transport-equation models, pdf models, and multiple-scale models. All these models are classified as one-point closure schemes since only one-point (in time and space) turbulent correlations, such as second moments (Reynolds stresses and turbulent heat fluxes) and third moments, are involved. In computational fluid dynamics, all turbulent quantities are one-point correlations. Therefore, the study of one-point turbulent closure schemes is the focus of our turbulence research. However, other research, such as the renormalization group theory, the direct interaction approximation method, and numerical simulations are also pursued to support the development of turbulence modeling.

Interactive Retro-Deformation of Terrain for Reconstructing 3D Fault Displacements.

PubMed

Westerteiger, R; Compton, T; Bernadin, T; Cowgill, E; Gwinner, K; Hamann, B; Gerndt, A; Hagen, H

2012-12-01

Planetary topography is the result of complex interactions between geological processes, of which faulting is a prominent component. Surface-rupturing earthquakes cut and move landforms which develop across active faults, producing characteristic surface displacements across the fault. Geometric models of faults and their associated surface displacements are commonly applied to reconstruct these offsets to enable interpretation of the observed topography. However, current 2D techniques are limited in their capability to convey both the three-dimensional kinematics of faulting and the incremental sequence of events required by a given reconstruction. Here we present a real-time system for interactive retro-deformation of faulted topography to enable reconstruction of fault displacement within a high-resolution (sub 1m/pixel) 3D terrain visualization. We employ geometry shaders on the GPU to intersect the surface mesh with fault-segments interactively specified by the user and transform the resulting surface blocks in realtime according to a kinematic model of fault motion. Our method facilitates a human-in-the-loop approach to reconstruction of fault displacements by providing instant visual feedback while exploring the parameter space. Thus, scientists can evaluate the validity of traditional point-to-point reconstructions by visually examining a smooth interpolation of the displacement in 3D. We show the efficacy of our approach by using it to reconstruct segments of the San Andreas fault, California as well as a graben structure in the Noctis Labyrinthus region on Mars.

Structure of the Acinetobacter baumannii Dithiol Oxidase DsbA Bound to Elongation Factor EF-Tu Reveals a Novel Protein Interaction Site

PubMed Central

Premkumar, Lakshmanane; Kurth, Fabian; Duprez, Wilko; Grøftehauge, Morten K.; King, Gordon J.; Halili, Maria A.; Heras, Begoña; Martin, Jennifer L.

2014-01-01

The multidrug resistant bacterium Acinetobacter baumannii is a significant cause of nosocomial infection. Biofilm formation, that requires both disulfide bond forming and chaperone-usher pathways, is a major virulence trait in this bacterium. Our biochemical characterizations show that the periplasmic A. baumannii DsbA (AbDsbA) enzyme has an oxidizing redox potential and dithiol oxidase activity. We found an unexpected non-covalent interaction between AbDsbA and the highly conserved prokaryotic elongation factor, EF-Tu. EF-Tu is a cytoplasmic protein but has been localized extracellularly in many bacterial pathogens. The crystal structure of this complex revealed that the EF-Tu switch I region binds to the non-catalytic surface of AbDsbA. Although the physiological and pathological significance of a DsbA/EF-Tu association is unknown, peptides derived from the EF-Tu switch I region bound to AbDsbA with submicromolar affinity. We also identified a seven-residue DsbB-derived peptide that bound to AbDsbA with low micromolar affinity. Further characterization confirmed that the EF-Tu- and DsbB-derived peptides bind at two distinct sites. These data point to the possibility that the non-catalytic surface of DsbA is a potential substrate or regulatory protein interaction site. The two peptides identified in this work together with the newly characterized interaction site provide a novel starting point for inhibitor design targeting AbDsbA. PMID:24860094

Identification of driving network of cellular differentiation from single sample time course gene expression data

NASA Astrophysics Data System (ADS)

Chen, Ye; Wolanyk, Nathaniel; Ilker, Tunc; Gao, Shouguo; Wang, Xujing

Methods developed based on bifurcation theory have demonstrated their potential in driving network identification for complex human diseases, including the work by Chen, et al. Recently bifurcation theory has been successfully applied to model cellular differentiation. However, there one often faces a technical challenge in driving network prediction: time course cellular differentiation study often only contains one sample at each time point, while driving network prediction typically require multiple samples at each time point to infer the variation and interaction structures of candidate genes for the driving network. In this study, we investigate several methods to identify both the critical time point and the driving network through examination of how each time point affects the autocorrelation and phase locking. We apply these methods to a high-throughput sequencing (RNA-Seq) dataset of 42 subsets of thymocytes and mature peripheral T cells at multiple time points during their differentiation (GSE48138 from GEO). We compare the predicted driving genes with known transcription regulators of cellular differentiation. We will discuss the advantages and limitations of our proposed methods, as well as potential further improvements of our methods.

Complexity and diversity.

PubMed

Doebeli, Michael; Ispolatov, Iaroslav

2010-04-23

The mechanisms for the origin and maintenance of biological diversity are not fully understood. It is known that frequency-dependent selection, generating advantages for rare types, can maintain genetic variation and lead to speciation, but in models with simple phenotypes (that is, low-dimensional phenotype spaces), frequency dependence needs to be strong to generate diversity. However, we show that if the ecological properties of an organism are determined by multiple traits with complex interactions, the conditions needed for frequency-dependent selection to generate diversity are relaxed to the point where they are easily satisfied in high-dimensional phenotype spaces. Mathematically, this phenomenon is reflected in properties of eigenvalues of quadratic forms. Because all living organisms have at least hundreds of phenotypes, this casts the potential importance of frequency dependence for the origin and maintenance of diversity in a new light.

Regime shifts and panarchies in regional scale social-ecological water systems

PubMed Central

Gunderson, Lance; Cosens, Barbara A.; Chaffin, Brian C.; (Tom) Arnold, Craig A.; Fremier, Alexander K.; Garmestani, Ahjond S.; Craig, Robin Kundis; Gosnell, Hannah; Birge, Hannah E.; Allen, Craig R.; Benson, Melinda H.; Morrison, Ryan R.; Stone, Mark C.; Hamm, Joseph A.; Nemec, Kristine; Schlager, Edella; Llewellyn, Dagmar

2018-01-01

In this article we summarize histories of nonlinear, complex interactions among societal, legal, and ecosystem dynamics in six North American water basins, as they respond to changing climate. These case studies were chosen to explore the conditions for emergence of adaptive governance in heavily regulated and developed social-ecological systems nested within a hierarchical governmental system. We summarize resilience assessments conducted in each system to provide a synthesis and reference by the other articles in this special feature. We also present a general framework used to evaluate the interactions between society and ecosystem regimes and the governance regimes chosen to mediate those interactions. The case studies show different ways that adaptive governance may be triggered, facilitated, or constrained by ecological and/or legal processes. The resilience assessments indicate that complex interactions among the governance and ecosystem components of these systems can produce different trajectories, which include patterns of (a) development and stabilization, (b) cycles of crisis and recovery, which includes lurches in adaptation and learning, and (3) periods of innovation, novelty, and transformation. Exploration of cross scale (Panarchy) interactions among levels and sectors of government and society illustrate that they may constrain development trajectories, but may also provide stability during crisis or innovation at smaller scales; create crises, but may also facilitate recovery; and constrain system transformation, but may also provide windows of opportunity in which transformation, and the resources to accomplish it, may occur. The framework is the starting point for our exploration of how law might play a role in enhancing the capacity of social-ecological systems to adapt to climate change. PMID:29780427

Regime shifts and panarchies in regional scale social-ecological water systems.

PubMed

Gunderson, Lance; Cosens, Barbara A; Chaffin, Brian C; Tom Arnold, Craig A; Fremier, Alexander K; Garmestani, Ahjond S; Craig, Robin Kundis; Gosnell, Hannah; Birge, Hannah E; Allen, Craig R; Benson, Melinda H; Morrison, Ryan R; Stone, Mark C; Hamm, Joseph A; Nemec, Kristine; Schlager, Edella; Llewellyn, Dagmar

2017-03-17

In this article we summarize histories of nonlinear, complex interactions among societal, legal, and ecosystem dynamics in six North American water basins, as they respond to changing climate. These case studies were chosen to explore the conditions for emergence of adaptive governance in heavily regulated and developed social-ecological systems nested within a hierarchical governmental system. We summarize resilience assessments conducted in each system to provide a synthesis and reference by the other articles in this special feature. We also present a general framework used to evaluate the interactions between society and ecosystem regimes and the governance regimes chosen to mediate those interactions. The case studies show different ways that adaptive governance may be triggered, facilitated, or constrained by ecological and/or legal processes. The resilience assessments indicate that complex interactions among the governance and ecosystem components of these systems can produce different trajectories, which include patterns of (a) development and stabilization, (b) cycles of crisis and recovery, which includes lurches in adaptation and learning, and (3) periods of innovation, novelty, and transformation. Exploration of cross scale (Panarchy) interactions among levels and sectors of government and society illustrate that they may constrain development trajectories, but may also provide stability during crisis or innovation at smaller scales; create crises, but may also facilitate recovery; and constrain system transformation, but may also provide windows of opportunity in which transformation, and the resources to accomplish it, may occur. The framework is the starting point for our exploration of how law might play a role in enhancing the capacity of social-ecological systems to adapt to climate change.

Regime shifts and panarchies in regional scale social-ecological water systems

USGS Publications Warehouse

Gunderson, Lance; Cosens, Barbara; Chaffin, Brian C.; Arnold, Craig Anthony (Tony); Fremier, Alexander K.; Garmestani, Ahjond S.; Kundis Craig, Robin; Gosnell, Hannah; Birge, Hannah E.; Allen, Craig R.; Benson, Melinda H.; Morrison, Ryan R.; Stone, Mark; Hamm, Joseph A.; Nemec, Kristine T.; Schlager, Edella; Llewellyn, Dagmar

2017-01-01

In this article we summarize histories of nonlinear, complex interactions among societal, legal, and ecosystem dynamics in six North American water basins, as they respond to changing climate. These case studies were chosen to explore the conditions for emergence of adaptive governance in heavily regulated and developed social-ecological systems nested within a hierarchical governmental system. We summarize resilience assessments conducted in each system to provide a synthesis and reference by the other articles in this special feature. We also present a general framework used to evaluate the interactions between society and ecosystem regimes and the governance regimes chosen to mediate those interactions. The case studies show different ways that adaptive governance may be triggered, facilitated, or constrained by ecological and/or legal processes. The resilience assessments indicate that complex interactions among the governance and ecosystem components of these systems can produce different trajectories, which include patterns of (a) development and stabilization, (b) cycles of crisis and recovery, which includes lurches in adaptation and learning, and (3) periods of innovation, novelty, and transformation. Exploration of cross scale (Panarchy) interactions among levels and sectors of government and society illustrate that they may constrain development trajectories, but may also provide stability during crisis or innovation at smaller scales; create crises, but may also facilitate recovery; and constrain system transformation, but may also provide windows of opportunity in which transformation, and the resources to accomplish it, may occur. The framework is the starting point for our exploration of how law might play a role in enhancing the capacity of social-ecological systems to adapt to climate change.

Synergizing Noncovalent Bonding Interactions in the Self-Assembly of Organic Charge-Transfer Ferroelectrics and Metal-Organic Frameworks

NASA Astrophysics Data System (ADS)

Cao, Dennis

Contemporary supramolecular chemistry---chemistry beyond the molecule---seeks to leverage noncovalent bonding interactions to generate emergent properties and complexity. These aims extend beyond the solution phase and into the solid state, where crystalline organic materials have attracted much attention for their ability to imitate the physical properties of inorganic crystals. This Thesis outlines my efforts to understand the properties of the solid-state materials that are self-assembled with noncovalent bonding motifs which I have helped to realize. In the first five Chapters, I chronicle the development of the lock-arm supramolecular ordering (LASO) paradigm, which is a general molecular design strategy for amplifying the crystallization of charge transfer complexes that revolves around the synergistic action of hydrogen bonding and charge transfer interactions. In an effort to expand upon the LASO paradigm, I identify a two-point halogen-bonding motif which appears to operate orthogonally from the hydrogen bonding and charge transfer interactions. Since some of these single crystalline materials are ferroelectric at room temperature, I discuss the implications of these experimental observations and reconcile them with the centrosymmetric space groups assigned after X-ray crystallographic refinements. I conclude in the final two Chapters by recording my endeavors to control the assembly of metal-organic frameworks (MOFs) with noncovalent bonding interactions between [2]catenane-bearing struts. First of all, I describe the formation of syndiotactic pi-stacked 2D MOF layers before highlighting a two-component MOF that assembles with a magic number ratio of components that is independent of the molar proportions present in the crystallization medium.

Mutations in the substrate binding site of human heat-shock protein 70 indicate specific interaction with HLA-DR outside the peptide binding groove

PubMed Central

Rohrer, Karin M; Haug, Markus; Schwörer, Daniela; Kalbacher, Hubert; Holzer, Ursula

2014-01-01

Heat-shock protein 70 (Hsp70)–peptide complexes are involved in MHC class I-and II-restricted antigen presentation, enabling enhanced activation of T cells. As shown previously, mammalian cytosolic Hsp70 (Hsc70) molecules interact specifically with HLA-DR molecules. This interaction might be of significance as Hsp70 molecules could transfer bound antigenic peptides in a ternary complex into the binding groove of HLA-DR molecules. The present study provides new insights into the distinct interaction of Hsp70 with HLA-DR molecules. Using a quantitative binding assay, it could be demonstrated that a point mutation of amino acids alanine 406 and valine 438 in the substrate binding pocket led to reduced peptide binding compared with the wild-type Hsp70 whereas HLA-DR binding remains unaffected. The removal of the C-terminal lid neither altered the substrate binding capacity nor the Hsp70 binding characteristics to HLA-DR. A truncated variant lacking the nucleotide binding domain showed no binding interactions with HLA-DR. Furthermore, the truncated ATPase subunit of constitutively expressed Hsc70 revealed similar binding affinities to HLA-DR compared with the complete Hsc70. Hence, it can be assumed that the Hsp70–HLA-DR interaction takes place outside the peptide binding groove and is attributed to the ATPase domain of HSP70 molecules. The Hsp70-chaperoned peptides might thereby be directly transferred into the binding groove of HLA-DR, so enabling enhanced presentation of the peptide on antigen-presenting cells and leading to an improved proliferation of responding T cells as shown previously. PMID:24428437

Energy variational analysis of ions in water and channels: Field theory for primitive models of complex ionic fluids

PubMed Central

Eisenberg, Bob; Hyon, YunKyong; Liu, Chun

2010-01-01

Ionic solutions are mixtures of interacting anions and cations. They hardly resemble dilute gases of uncharged noninteracting point particles described in elementary textbooks. Biological and electrochemical solutions have many components that interact strongly as they flow in concentrated environments near electrodes, ion channels, or active sites of enzymes. Interactions in concentrated environments help determine the characteristic properties of electrodes, enzymes, and ion channels. Flows are driven by a combination of electrical and chemical potentials that depend on the charges, concentrations, and sizes of all ions, not just the same type of ion. We use a variational method EnVarA (energy variational analysis) that combines Hamilton’s least action and Rayleigh’s dissipation principles to create a variational field theory that includes flow, friction, and complex structure with physical boundary conditions. EnVarA optimizes both the action integral functional of classical mechanics and the dissipation functional. These functionals can include entropy and dissipation as well as potential energy. The stationary point of the action is determined with respect to the trajectory of particles. The stationary point of the dissipation is determined with respect to rate functions (such as velocity). Both variations are written in one Eulerian (laboratory) framework. In variational analysis, an “extra layer” of mathematics is used to derive partial differential equations. Energies and dissipations of different components are combined in EnVarA and Euler–Lagrange equations are then derived. These partial differential equations are the unique consequence of the contributions of individual components. The form and parameters of the partial differential equations are determined by algebra without additional physical content or assumptions. The partial differential equations of mixtures automatically combine physical properties of individual (unmixed) components. If a new component is added to the energy or dissipation, the Euler–Lagrange equations change form and interaction terms appear without additional adjustable parameters. EnVarA has previously been used to compute properties of liquid crystals, polymer fluids, and electrorheological fluids containing solid balls and charged oil droplets that fission and fuse. Here we apply EnVarA to the primitive model of electrolytes in which ions are spheres in a frictional dielectric. The resulting Euler–Lagrange equations include electrostatics and diffusion and friction. They are a time dependent generalization of the Poisson–Nernst–Planck equations of semiconductors, electrochemistry, and molecular biophysics. They include the finite diameter of ions. The EnVarA treatment is applied to ions next to a charged wall, where layering is observed. Applied to an ion channel, EnVarA calculates a quick transient pile-up of electric charge, transient and steady flow through the channel, stationary “binding” in the channel, and the eventual accumulation of salts in “unstirred layers” near channels. EnVarA treats electrolytes in a unified way as complex rather than simple fluids. Ad hoc descriptions of interactions and flow have been used in many areas of science to deal with the nonideal properties of electrolytes. It seems likely that the variational treatment can simplify, unify, and perhaps derive and improve those descriptions. PMID:20849161

Power transformations improve interpolation of grids for molecular mechanics interaction energies.

PubMed

Minh, David D L

2018-02-18

A common strategy for speeding up molecular docking calculations is to precompute nonbonded interaction energies between a receptor molecule and a set of three-dimensional grids. The grids are then interpolated to compute energies for ligand atoms in many different binding poses. Here, I evaluate a smoothing strategy of taking a power transformation of grid point energies and inverse transformation of the result from trilinear interpolation. For molecular docking poses from 85 protein-ligand complexes, this smoothing procedure leads to significant accuracy improvements, including an approximately twofold reduction in the root mean square error at a grid spacing of 0.4 Å and retaining the ability to rank docking poses even at a grid spacing of 0.7 Å. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Multivariate spatiotemporal visualizations for mobile devices in Flyover Country

NASA Astrophysics Data System (ADS)

Loeffler, S.; Thorn, R.; Myrbo, A.; Roth, R.; Goring, S. J.; Williams, J.

2017-12-01

Visualizing and interacting with complex multivariate and spatiotemporal datasets on mobile devices is challenging due to their smaller screens, reduced processing power, and limited data connectivity. Pollen data require visualizing pollen assemblages spatially, temporally, and across multiple taxa to understand plant community dynamics through time. Drawing from cartography, information visualization, and paleoecology, we have created new mobile-first visualization techniques that represent multiple taxa across many sites and enable user interaction. Using pollen datasets from the Neotoma Paleoecology Database as a case study, the visualization techniques allow ecological patterns and trends to be quickly understood on a mobile device compared to traditional pollen diagrams and maps. This flexible visualization system can be used for datasets beyond pollen, with the only requirements being point-based localities and multiple variables changing through time or depth.

Storm and tide influenced depositional architecture of the Pliocene-Pleistocene Chad Formation, Chad Basin (Bornu Sub-basin) NE Nigeria: A mixed fluvial, deltaic, shoreface and lacustrine complex

NASA Astrophysics Data System (ADS)

Shettima, Bukar; Kyari, Aji Maina; Aji, Mallam Musa; Adams, Fatimoh Dupe

2018-07-01

Lithofacies analyses of the upper part of the Chad Formation (Bama Ridge Complex) in the Bornu Sub-basin of the Chad Basin indicated four facies associations; fluvial, deltaic, shoreface and lacustrine sequences. The fluvial sequences are composed of fining upward cycles with successive occurrence of planar crossbedded sandstone facies displaying unimodal paleocurrent system and rare mudstone facies typical of braided river system. The deltaic succession consists of both fining and coarsening upwards cycles with the former depicting fluvial setting of an upper delta plain while the later suggestive of mouth-bar sequences. The setting displays a polymodal current system of fluvial, waves, storms and tides that were primarily induced by complex interactions of seiches and lunar tides. Similar current systems devoid of fluvial patterns were reflected in the coarsening upward packages of the shoreface sequences. Lacustrine succession composed of thick bioturbated mudstone facies generally defines the base of these coarsening upward profiles, giving a fluvio-lacustrine geomorphic relief where complex interaction developed the deltaic and shoreface facies along its shorelines. Clay mineral fractions of the formation are dominantly kaolinitic, indicating a predominantly humid tropical-subtropical climatic condition during their deposition. This climatic regime falls within the African humid period of the early-mid Holocene that led to the third lacustrine transgression of the Lake Mega-Chad, whereas the subordinate smectite mineralization points to aridification that characterizes most of the post humid period to recent.

Modeling complex metabolic reactions, ecological systems, and financial and legal networks with MIANN models based on Markov-Wiener node descriptors.

PubMed

Duardo-Sánchez, Aliuska; Munteanu, Cristian R; Riera-Fernández, Pablo; López-Díaz, Antonio; Pazos, Alejandro; González-Díaz, Humberto

2014-01-27

The use of numerical parameters in Complex Network analysis is expanding to new fields of application. At a molecular level, we can use them to describe the molecular structure of chemical entities, protein interactions, or metabolic networks. However, the applications are not restricted to the world of molecules and can be extended to the study of macroscopic nonliving systems, organisms, or even legal or social networks. On the other hand, the development of the field of Artificial Intelligence has led to the formulation of computational algorithms whose design is based on the structure and functioning of networks of biological neurons. These algorithms, called Artificial Neural Networks (ANNs), can be useful for the study of complex networks, since the numerical parameters that encode information of the network (for example centralities/node descriptors) can be used as inputs for the ANNs. The Wiener index (W) is a graph invariant widely used in chemoinformatics to quantify the molecular structure of drugs and to study complex networks. In this work, we explore for the first time the possibility of using Markov chains to calculate analogues of node distance numbers/W to describe complex networks from the point of view of their nodes. These parameters are called Markov-Wiener node descriptors of order k(th) (W(k)). Please, note that these descriptors are not related to Markov-Wiener stochastic processes. Here, we calculated the W(k)(i) values for a very high number of nodes (>100,000) in more than 100 different complex networks using the software MI-NODES. These networks were grouped according to the field of application. Molecular networks include the Metabolic Reaction Networks (MRNs) of 40 different organisms. In addition, we analyzed other biological and legal and social networks. These include the Interaction Web Database Biological Networks (IWDBNs), with 75 food webs or ecological systems and the Spanish Financial Law Network (SFLN). The calculated W(k)(i) values were used as inputs for different ANNs in order to discriminate correct node connectivity patterns from incorrect random patterns. The MIANN models obtained present good values of Sensitivity/Specificity (%): MRNs (78/78), IWDBNs (90/88), and SFLN (86/84). These preliminary results are very promising from the point of view of a first exploratory study and suggest that the use of these models could be extended to the high-throughput re-evaluation of connectivity in known complex networks (collation).

Inferring coarse-grain histone-DNA interaction potentials from high-resolution structures of the nucleosome

NASA Astrophysics Data System (ADS)

Meyer, Sam; Everaers, Ralf

2015-02-01

The histone-DNA interaction in the nucleosome is a fundamental mechanism of genomic compaction and regulation, which remains largely unknown despite increasing structural knowledge of the complex. In this paper, we propose a framework for the extraction of a nanoscale histone-DNA force-field from a collection of high-resolution structures, which may be adapted to a larger class of protein-DNA complexes. We applied the procedure to a large crystallographic database extended by snapshots from molecular dynamics simulations. The comparison of the structural models first shows that, at histone-DNA contact sites, the DNA base-pairs are shifted outwards locally, consistent with locally repulsive forces exerted by the histones. The second step shows that the various force profiles of the structures under analysis derive locally from a unique, sequence-independent, quadratic repulsive force-field, while the sequence preferences are entirely due to internal DNA mechanics. We have thus obtained the first knowledge-derived nanoscale interaction potential for histone-DNA in the nucleosome. The conformations obtained by relaxation of nucleosomal DNA with high-affinity sequences in this potential accurately reproduce the experimental values of binding preferences. Finally we address the more generic binding mechanisms relevant to the 80% genomic sequences incorporated in nucleosomes, by computing the conformation of nucleosomal DNA with sequence-averaged properties. This conformation differs from those found in crystals, and the analysis suggests that repulsive histone forces are related to local stretch tension in nucleosomal DNA, mostly between adjacent contact points. This tension could play a role in the stability of the complex.

Evaluation of Intersection Traffic Control Measures through Simulation

NASA Astrophysics Data System (ADS)

Asaithambi, Gowri; Sivanandan, R.

2015-12-01

Modeling traffic flow is stochastic in nature due to randomness in variables such as vehicle arrivals and speeds. Due to this and due to complex vehicular interactions and their manoeuvres, it is extremely difficult to model the traffic flow through analytical methods. To study this type of complex traffic system and vehicle interactions, simulation is considered as an effective tool. Application of homogeneous traffic models to heterogeneous traffic may not be able to capture the complex manoeuvres and interactions in such flows. Hence, a microscopic simulation model for heterogeneous traffic is developed using object oriented concepts. This simulation model acts as a tool for evaluating various control measures at signalized intersections. The present study focuses on the evaluation of Right Turn Lane (RTL) and Channelised Left Turn Lane (CLTL). A sensitivity analysis was performed to evaluate RTL and CLTL by varying the approach volumes, turn proportions and turn lane lengths. RTL is found to be advantageous only up to certain approach volumes and right-turn proportions, beyond which it is counter-productive. CLTL is found to be advantageous for lower approach volumes for all turn proportions, signifying the benefits of CLTL. It is counter-productive for higher approach volume and lower turn proportions. This study pinpoints the break-even points for various scenarios. The developed simulation model can be used as an appropriate intersection lane control tool for enhancing the efficiency of flow at intersections. This model can also be employed for scenario analysis and can be valuable to field traffic engineers in implementing vehicle-type based and lane-based traffic control measures.

Coevolution study of mitochondria respiratory chain proteins: toward the understanding of protein--protein interaction.

PubMed

Yang, Ming; Ge, Yan; Wu, Jiayan; Xiao, Jingfa; Yu, Jun

2011-05-20

Coevolution can be seen as the interdependency between evolutionary histories. In the context of protein evolution, functional correlation proteins are ever-present coordinated evolutionary characters without disruption of organismal integrity. As to complex system, there are two forms of protein--protein interactions in vivo, which refer to inter-complex interaction and intra-complex interaction. In this paper, we studied the difference of coevolution characters between inter-complex interaction and intra-complex interaction using "Mirror tree" method on the respiratory chain (RC) proteins. We divided the correlation coefficients of every pairwise RC proteins into two groups corresponding to the binary protein--protein interaction in intra-complex and the binary protein--protein interaction in inter-complex, respectively. A dramatical discrepancy is detected between the coevolution characters of the two sets of protein interactions (Wilcoxon test, p-value = 4.4 × 10(-6)). Our finding reveals some critical information on coevolutionary study and assists the mechanical investigation of protein--protein interaction. Furthermore, the results also provide some unique clue for supramolecular organization of protein complexes in the mitochondrial inner membrane. More detailed binding sites map and genome information of nuclear encoded RC proteins will be extraordinary valuable for the further mitochondria dynamics study. Copyright © 2011. Published by Elsevier Ltd.