On complexity and homogeneity measures in predicting biological aggressiveness of prostate cancer; Implication of the cellular automata model of tumor growth.

PubMed

Tanase, Mihai; Waliszewski, Przemyslaw

2015-12-01

We propose a novel approach for the quantitative evaluation of aggressiveness in prostate carcinomas. The spatial distribution of cancer cell nuclei was characterized by the global spatial fractal dimensions D0, D1, and D2. Two hundred eighteen prostate carcinomas were stratified into the classes of equivalence using results of ROC analysis. A simulation of the cellular automata mix defined a theoretical frame for a specific geometric representation of the cell nuclei distribution called a local structure correlation diagram (LSCD). The LSCD and dispersion Hd were computed for each carcinoma. Data mining generated some quantitative criteria describing tumor aggressiveness. Alterations in tumor architecture along progression were associated with some changes in both shape and the quantitative characteristics of the LSCD consistent with those in the automata mix model. Low-grade prostate carcinomas with low complexity and very low biological aggressiveness are defined by the condition D0 < 1.545 and Hd < 38. High-grade carcinomas with high complexity and very high biological aggressiveness are defined by the condition D0 > 1.764 and Hd < 38. The novel homogeneity measure Hd identifies carcinomas with very low aggressiveness within the class of complexity C1 or carcinomas with very high aggressiveness in the class C7. © 2015 Wiley Periodicals, Inc.

On operational flood forecasting system involving 1D/2D coupled hydraulic model and data assimilation

NASA Astrophysics Data System (ADS)

Barthélémy, S.; Ricci, S.; Morel, T.; Goutal, N.; Le Pape, E.; Zaoui, F.

2018-07-01

In the context of hydrodynamic modeling, the use of 2D models is adapted in areas where the flow is not mono-dimensional (confluence zones, flood plains). Nonetheless the lack of field data and the computational cost constraints limit the extensive use of 2D models for operational flood forecasting. Multi-dimensional coupling offers a solution with 1D models where the flow is mono-dimensional and with local 2D models where needed. This solution allows for the representation of complex processes in 2D models, while the simulated hydraulic state is significantly better than that of the full 1D model. In this study, coupling is implemented between three 1D sub-models and a local 2D model for a confluence on the Adour river (France). A Schwarz algorithm is implemented to guarantee the continuity of the variables at the 1D/2D interfaces while in situ observations are assimilated in the 1D sub-models to improve results and forecasts in operational mode as carried out by the French flood forecasting services. An implementation of the coupling and data assimilation (DA) solution with domain decomposition and task/data parallelism is proposed so that it is compatible with operational constraints. The coupling with the 2D model improves the simulated hydraulic state compared to a global 1D model, and DA improves results in 1D and 2D areas.

Nonlinear complexity behaviors of agent-based 3D Potts financial dynamics with random environments

NASA Astrophysics Data System (ADS)

Xing, Yani; Wang, Jun

2018-02-01

A new microscopic 3D Potts interaction financial price model is established in this work, to investigate the nonlinear complexity behaviors of stock markets. 3D Potts model, which extends the 2D Potts model to three-dimensional, is a cubic lattice model to explain the interaction behavior among the agents. In order to explore the complexity of real financial markets and the 3D Potts financial model, a new random coarse-grained Lempel-Ziv complexity is proposed to certain series, such as the price returns, the price volatilities, and the random time d-returns. Then the composite multiscale entropy (CMSE) method is applied to the intrinsic mode functions (IMFs) and the corresponding shuffled data to study the complexity behaviors. The empirical results indicate that the 3D financial model is feasible.

Multi-scale modeling of tsunami flows and tsunami-induced forces

NASA Astrophysics Data System (ADS)

Qin, X.; Motley, M. R.; LeVeque, R. J.; Gonzalez, F. I.

2016-12-01

The modeling of tsunami flows and tsunami-induced forces in coastal communities with the incorporation of the constructed environment is challenging for many numerical modelers because of the scale and complexity of the physical problem. A two-dimensional (2D) depth-averaged model can be efficient for modeling of waves offshore but may not be accurate enough to predict the complex flow with transient variance in vertical direction around constructed environments on land. On the other hand, using a more complex three-dimensional model is much more computational expensive and can become impractical due to the size of the problem and the meshing requirements near the built environment. In this study, a 2D depth-integrated model and a 3D Reynolds Averaged Navier-Stokes (RANS) model are built to model a 1:50 model-scale, idealized community, representative of Seaside, OR, USA, for which existing experimental data is available for comparison. Numerical results from the two numerical models are compared with each other as well as experimental measurement. Both models predict the flow parameters (water level, velocity, and momentum flux in the vicinity of the buildings) accurately, in general, except for time period near the initial impact, where the depth-averaged models can fail to capture the complexities in the flow. Forces predicted using direct integration of predicted pressure on structural surfaces from the 3D model and using momentum flux from the 2D model with constructed environment are compared, which indicates that force prediction from the 2D model is not always reliable in such a complicated case. Force predictions from integration of the pressure are also compared with forces predicted from bare earth momentum flux calculations to reveal the importance of incorporating the constructed environment in force prediction models.

The Role of Model Complexity in Determining Patterns of Chlorophyll Variability in the Coastal Northwest North Atlantic

NASA Astrophysics Data System (ADS)

Kuhn, A. M.; Fennel, K.; Bianucci, L.

2016-02-01

A key feature of the North Atlantic Ocean's biological dynamics is the annual phytoplankton spring bloom. In the region comprising the continental shelf and adjacent deep ocean of the northwest North Atlantic, we identified two patterns of bloom development: 1) locations with cold temperatures and deep winter mixed layers, where the spring bloom peaks around April and the annual chlorophyll cycle has a large amplitude, and 2) locations with warmer temperatures and shallow winter mixed layers, where the spring bloom peaks earlier in the year, sometimes indiscernible from the fall bloom. These patterns result from a combination of limiting environmental factors and interactions among planktonic groups with different optimal requirements. Simple models that represent the ecosystem with a single phytoplankton (P) and a single zooplankton (Z) group are challenged to reproduce these ecological interactions. Here we investigate the effect that added complexity has on determining spatio-temporal chlorophyll. We compare two ecosystem models, one that contains one P and one Z group, and one with two P and three Z groups. We consider three types of changes in complexity: 1) added dependencies among variables (e.g., temperature dependent rates), 2) modified structural pathways, and 3) added pathways. Subsets of the most sensitive parameters are optimized in each model to replicate observations in the region. For computational efficiency, the parameter optimization is performed using 1D surrogates of a 3D model. We evaluate how model complexity affects model skill, and whether the optimized parameter sets found for each model modify the interpretation of ecosystem functioning. Spatial differences in the parameter sets that best represent different areas hint at the existence of different ecological communities or at physical-biological interactions that are not represented in the simplest model. Our methodology emphasizes the combined use of observations, 1D models to help identifying patterns, and 3D models able to simulate the environment modre realistically, as a means to acquire predictive understanding of the ocean's ecology.

A complex fermionic tensor model in d dimensions

NASA Astrophysics Data System (ADS)

Prakash, Shiroman; Sinha, Ritam

2018-02-01

In this note, we study a melonic tensor model in d dimensions based on three-index Dirac fermions with a four-fermion interaction. Summing the melonic diagrams at strong coupling allows one to define a formal large- N saddle point in arbitrary d and calculate the spectrum of scalar bilinear singlet operators. For d = 2 - ɛ the theory is an infrared fixed point, which we find has a purely real spectrum that we determine numerically for arbitrary d < 2, and analytically as a power series in ɛ. The theory appears to be weakly interacting when ɛ is small, suggesting that fermionic tensor models in 1-dimension can be studied in an ɛ expansion. For d > 2, the spectrum can still be calculated using the saddle point equations, which may define a formal large- N ultraviolet fixed point analogous to the Gross-Neveu model in d > 2. For 2 < d < 6, we find that the spectrum contains at least one complex scalar eigenvalue (similar to the complex eigenvalue present in the bosonic tensor model recently studied by Giombi, Klebanov and Tarnopolsky) which indicates that the theory is unstable. We also find that the fixed point is weakly-interacting when d = 6 (or more generally d = 4 n + 2) and has a real spectrum for 6 < d < 6 .14 which we present as a power series in ɛ in 6 + ɛ dimensions.

Emergent 1d Ising Behavior in AN Elementary Cellular Automaton Model

NASA Astrophysics Data System (ADS)

Kassebaum, Paul G.; Iannacchione, Germano S.

The fundamental nature of an evolving one-dimensional (1D) Ising model is investigated with an elementary cellular automaton (CA) simulation. The emergent CA simulation employs an ensemble of cells in one spatial dimension, each cell capable of two microstates interacting with simple nearest-neighbor rules and incorporating an external field. The behavior of the CA model provides insight into the dynamics of coupled two-state systems not expressible by exact analytical solutions. For instance, state progression graphs show the causal dynamics of a system through time in relation to the system's entropy. Unique graphical analysis techniques are introduced through difference patterns, diffusion patterns, and state progression graphs of the 1D ensemble visualizing the evolution. All analyses are consistent with the known behavior of the 1D Ising system. The CA simulation and new pattern recognition techniques are scalable (in both dimension, complexity, and size) and have many potential applications such as complex design of materials, control of agent systems, and evolutionary mechanism design.

A Structural Study of CESA1 Catalytic Domain of Arabidopsis Cellulose Synthesis Complex: Evidence for CESA Trimers1

PubMed Central

Zhang, Qiu; Petridis, Loukas; Nixon, B. Tracy; Haigler, Candace H.; Kalluri, Udaya; Coates, Leighton; Smith, Jeremy C.; Meiler, Jens

2016-01-01

A cellulose synthesis complex with a “rosette” shape is responsible for synthesis of cellulose chains and their assembly into microfibrils within the cell walls of land plants and their charophyte algal progenitors. The number of cellulose synthase proteins in this large multisubunit transmembrane protein complex and the number of cellulose chains in a microfibril have been debated for many years. This work reports a low resolution structure of the catalytic domain of CESA1 from Arabidopsis (Arabidopsis thaliana; AtCESA1CatD) determined by small-angle scattering techniques and provides the first experimental evidence for the self-assembly of CESA into a stable trimer in solution. The catalytic domain was overexpressed in Escherichia coli, and using a two-step procedure, it was possible to isolate monomeric and trimeric forms of AtCESA1CatD. The conformation of monomeric and trimeric AtCESA1CatD proteins were studied using small-angle neutron scattering and small-angle x-ray scattering. A series of AtCESA1CatD trimer computational models were compared with the small-angle x-ray scattering trimer profile to explore the possible arrangement of the monomers in the trimers. Several candidate trimers were identified with monomers oriented such that the newly synthesized cellulose chains project toward the cell membrane. In these models, the class-specific region is found at the periphery of the complex, and the plant-conserved region forms the base of the trimer. This study strongly supports the “hexamer of trimers” model for the rosette cellulose synthesis complex that synthesizes an 18-chain cellulose microfibril as its fundamental product. PMID:26556795

Structure and equilibria of Ca 2+-complexes of glucose and sorbitol from multinuclear ( 1H, 13C and 43Ca) NMR measurements supplemented with molecular modelling calculations

NASA Astrophysics Data System (ADS)

Pallagi, A.; Dudás, Cs.; Csendes, Z.; Forgó, P.; Pálinkó, I.; Sipos, P.

2011-05-01

Ca 2+-complexation of D-glucose and D-sorbitol have been investigated with the aid of multinuclear ( 1H, 13C and 43Ca) NMR spectroscopy and ab initio quantum chemical calculations. Formation constants of the forming 1:1 complexes have been estimated from one-dimensional 13C NMR spectra obtained at constant ionic strength (1 M NaCl). Binding sites were identified from 2D 1H- 43Ca NMR spectra. 2D NMR measurements and ab initio calculations indicated that Ca 2+ ions were bound in a tridentate manner via the glycosidic OH, the ethereal oxygen in the ring and the OH on the terminal carbon for the α- and β-anomers of glucose and for sorbitol simultaneous binding of four hydroxide moieties (C1, C2, C4 and C6) was suggested.

Host-guest complex formation in cyclotrikis-(1-->6).

PubMed

Cescutti, P; Utille, J P; Rizzo, R

2000-11-17

The possibility that cyclotrikis-(1-->6)-[alpha-D-glucopyranosyl-(1-->4)-beta-D-glucopyranosyl] (CGM6) forms inclusion complexes, like cycloamyloses (cyclodextrins), was investigated by means of electrospray mass spectrometry and fluorescence spectroscopy. The complexing ability of both 1-anilinonaphthalene-8-sulfonate (ANS) and 2-p-toluidinylnaphthalene-6-sulfonate (TNS), which were already used with cyclodextrins, was investigated. The former showed very little or no tendency to be complexed by CGM6, while the latter produced detectable adducts with CGM6. Fixed 90 degree angle light scattering experiments supported the findings obtained by molecular modelling calculations, which indicated a polar character for the CGM6 internal cavity. CGM6-TNS complexes were probably formed throughout interaction of the polar regions of the two molecules.

3D structure of the influenza virus polymerase complex: Localization of subunit domains

PubMed Central

Area, Estela; Martín-Benito, Jaime; Gastaminza, Pablo; Torreira, Eva; Valpuesta, José M.; Carrascosa, José L.; Ortín, Juan

2004-01-01

The 3D structure of the influenza virus polymerase complex was determined by electron microscopy and image processing of recombinant ribonucleoproteins (RNPs). The RNPs were generated by in vivo amplification using cDNAs of the three polymerase subunits, the nucleoprotein, and a model virus-associated RNA containing 248 nt. The polymerase structure obtained is very compact, with no apparent boundaries among subunits. The position of specific regions of the PB1, PB2, and PA subunits was determined by 3D reconstruction of either RNP–mAb complexes or tagged RNPs. This structural model is available for the polymerase of a negative-stranded RNA virus and provides a general delineation of the complex and its interaction with the template-associated nucleoprotein monomers in the RNP. PMID:14691253

A Structural Study of CESA1 Catalytic Domain of Arabidopsis Cellulose Synthesis Complex: Evidence for CESA Trimers.

PubMed

Vandavasi, Venu Gopal; Putnam, Daniel K; Zhang, Qiu; Petridis, Loukas; Heller, William T; Nixon, B Tracy; Haigler, Candace H; Kalluri, Udaya; Coates, Leighton; Langan, Paul; Smith, Jeremy C; Meiler, Jens; O'Neill, Hugh

2016-01-01

A cellulose synthesis complex with a "rosette" shape is responsible for synthesis of cellulose chains and their assembly into microfibrils within the cell walls of land plants and their charophyte algal progenitors. The number of cellulose synthase proteins in this large multisubunit transmembrane protein complex and the number of cellulose chains in a microfibril have been debated for many years. This work reports a low resolution structure of the catalytic domain of CESA1 from Arabidopsis (Arabidopsis thaliana; AtCESA1CatD) determined by small-angle scattering techniques and provides the first experimental evidence for the self-assembly of CESA into a stable trimer in solution. The catalytic domain was overexpressed in Escherichia coli, and using a two-step procedure, it was possible to isolate monomeric and trimeric forms of AtCESA1CatD. The conformation of monomeric and trimeric AtCESA1CatD proteins were studied using small-angle neutron scattering and small-angle x-ray scattering. A series of AtCESA1CatD trimer computational models were compared with the small-angle x-ray scattering trimer profile to explore the possible arrangement of the monomers in the trimers. Several candidate trimers were identified with monomers oriented such that the newly synthesized cellulose chains project toward the cell membrane. In these models, the class-specific region is found at the periphery of the complex, and the plant-conserved region forms the base of the trimer. This study strongly supports the "hexamer of trimers" model for the rosette cellulose synthesis complex that synthesizes an 18-chain cellulose microfibril as its fundamental product. © 2016 American Society of Plant Biologists. All Rights Reserved.

A Structural Study of CESA1 Catalytic Domain of Arabidopsis Cellulose Synthesis Complex: Evidence for CESA Trimers

DOE PAGES

Vandavasi, Venu Gopal; Putnam, Daniel K.; Zhang, Qiu; ...

2015-11-10

In a cellulose synthesis complex a "rosette" shape is responsible for the synthesis of cellulose chains and their assembly into microfibrils within the cell walls of land plants and their charophyte algal progenitors. The number of cellulose synthase proteins in this large multisubunit transmembrane protein complex and the number of cellulose chains in a microfibril have been debated for many years. Our work reports a low resolution structure of the catalytic domain of CESA1 from Arabidopsis (Arabidopsis thaliana; AtCESA1CatD) determined by small-angle scattering techniques and provides the first experimental evidence for the self-assembly of CESA into a stable trimer inmore » solution. The catalytic domain was overexpressed in Escherichia coli, and using a two-step procedure, it was possible to isolate monomeric and trimeric forms of AtCESA1CatD. Moreover, the conformation of monomeric and trimeric AtCESA1CatD proteins were studied using small-angle neutron scattering and small-angle x-ray scattering. A series of AtCESA1CatD trimer computational models were compared with the small-angle x-ray scattering trimer profile to explore the possible arrangement of the monomers in the trimers. Several candidate trimers were identified with monomers oriented such that the newly synthesized cellulose chains project toward the cell membrane. In these models, the class-specific region is found at the periphery of the complex, and the plant-conserved region forms the base of the trimer. Finally, this study strongly supports the "hexamer of trimers" model for the rosette cellulose synthesis complex that synthesizes an 18-chain cellulose microfibril as its fundamental product.« less

Constructing and Modifying Sequence Statistics for relevent Using informR in 𝖱

PubMed Central

Marcum, Christopher Steven; Butts, Carter T.

2015-01-01

The informR package greatly simplifies the analysis of complex event histories in 𝖱 by providing user friendly tools to build sufficient statistics for the relevent package. Historically, building sufficient statistics to model event sequences (of the form a→b) using the egocentric generalization of Butts’ (2008) relational event framework for modeling social action has been cumbersome. The informR package simplifies the construction of the complex list of arrays needed by the rem() model fitting for a variety of cases involving egocentric event data, multiple event types, and/or support constraints. This paper introduces these tools using examples from real data extracted from the American Time Use Survey. PMID:26185488

Synthesis, crystal structure and investigation of mononuclear copper(II) and zinc(II) complexes of a new carboxylate rich tripodal ligand and their interaction with carbohydrates in alkaline aqueous solution

PubMed Central

Stewart, Christopher D.; Pedraza, Mayra; Arman, Hadi; Fan, Hua-Jun; Schilling, Eduardo Luiz; Szpoganicz, Bruno; Musie, Ghezai T.

2016-01-01

A new carboxylate rich asymmetric tripodal ligand, N-[2-carboxybenzomethyl]-N-[carboxymethyl]-β-alanine (H3camb), and its di-copper(II), (NH4)2[1]2, and di-zinc(II), ((CH3)4 N)2[2]2, complexes have been synthesized as carbohydrate binding models in aqueous solutions. The ligand and complexes have been fully characterized using several techniques, including single crystal X-ray diffraction. The interactions of (NH4)2[1]2 and ((CH3)4 N)2[2]2 with D-glucose, D-mannose, D-xylose and xylitol in aqueous alkaline media were investigated using UV–Vis and 13C-NMR spectroscopic techniques, respectively. The molar conductance, NMR and ESI–MS studies indicate that the complexes dissociate in solution to produce the respective complex anions, 1− and 2−. Complexes 1− and 2− showed chelating ability towards the naturally abundant and biologically relevant sugars, D-glucose, D-mannose, D-xylose, and xylitol. The complex ions bind to one molar equivalent of the sugars, even in the presence of stoichiometric excess of the substrates, in solution. Experimentally obtained spectroscopic data and computational results suggest that the substrates bind to the metal center in a bidentate fashion. Apparent binding constant values, pKapp, between the complexes and the substrates were determined and a specific mode of substrate binding is proposed. The pKapp and relativistic density functional theory (DFT) calculated Gibbs free energy values indicate that D-mannose displayed the strongest interaction with the complexes. Syntheses, characterizations, detailed substrate binding studies using spectroscopic techniques, single crystal X-ray diffraction and geometry optimizations of the complex-substrates with DFT calculations are also reported. PMID:25969174

1H NMR studies of molecular interaction of D-glucosamine and N-acetyl-D-glucosamine with capsaicin in aqueous and non-aqueous media.

PubMed

Higuera-Ciapara, Inocencio; Virués, Claudia; Jiménez-Chávez, Marcela; Martínez-Benavidez, Evelin; Hernández, Javier; Domínguez, Zaira; López-Rendón, Roberto; Velázquez, Enrique F; Inoue, Motomichi

2017-11-27

Complex formation of D-glucosamine (Gl) and N-acetyl-D-glucosamine (AGl) with capsaicin (Cp) were studied by 1 H NMR titrations in H 2 O-d 2 and DMSO-d 6 ; capsaicin is the major bioactive component of chili peppers. Every titration curve has been interpreted by formulating a suitable model for the reaction equilibrium, to elucidate intermolecular interactions. In DMSO, glucosamine cations associate with each other to yield linear aggregates, and undergo pseudo-1:1-complexation with capsaicin, the formation constant being ca. 30 M -1 . N-Acetylglucosamine, without self-association, forms a 2:1-complex AGl 2 Cp with the stability of ca. 70 M -2 . These complexations are achieved by intermolecular hydrogen bonds. In D 2 O, glucosamine undergoes reversible protonation equilibrium between Gl 0 and GlH + with the logarithmic protonation constants log K D  = 8.63 for α-glucosamine and 8.20 for β-isomer. Both anomeric isomers of deprotonated glucosamine form Gl 0 Cp-type complexes of capsaicin, in a competitive manner, with a formation constant of 1040 M -1 for the α-glucosamine complex and 830 M -1 for the β-complex; the anomeric carbons result in the difference in thermodynamic stability. The reactant molecules are closed up by the solvent-exclusion effect and/or the van der Waals interaction; the resulting pair is stabilized by intermolecular hydrogen bonding within a local water-free space between the component molecules. By contrast, neither protonated glucosamine (GlH + ) nor N-acetylglucosamine yields a capsaicin complex with the definite stoichiometry. The monosaccharides recognize capsaicin under only a controlled condition; the same phenomena are predicted for biological systems and nanocarriers based on polysaccharides such as chitosan. Copyright © 2017 Elsevier Ltd. All rights reserved.

Non-ideality by sedimentation velocity of halophilic malate dehydrogenase in complex solvents.

PubMed Central

Solovyova, A; Schuck, P; Costenaro, L; Ebel, C

2001-01-01

We have investigated the potential of sedimentation velocity analytical ultracentrifugation for the measurement of the second virial coefficients of proteins, with the goal of developing a method that allows efficient screening of different solvent conditions. This may be useful for the study of protein crystallization. Macromolecular concentration distributions were modeled using the Lamm equation with the approximation of linear concentration dependencies of the diffusion constant, D = D(o) (1 + k(D)c), and the reciprocal sedimentation coefficient s = s(o)/(1 + k(s)c). We have studied model distributions for their information content with respect to the particle and its non-ideal behavior, developed a strategy for their analysis by direct boundary modeling, and applied it to data from sedimentation velocity experiments on halophilic malate dehydrogenase in complex aqueous solvents containing sodium chloride and 2-methyl-2,4-pentanediol, including conditions near phase separation. Using global modeling for three sets of data obtained at three different protein concentrations, very good estimates for k(s) and s degrees and also for D degrees and the buoyant molar mass were obtained. It was also possible to obtain good estimates for k(D) and the second virial coefficients. Modeling of sedimentation velocity profiles with the non-ideal Lamm equation appears as a good technique to investigate weak inter-particle interactions in complex solvents and also to extrapolate the ideal behavior of the particle. PMID:11566761

Capturing tumor complexity in vitro: Comparative analysis of 2D and 3D tumor models for drug discovery.

PubMed

Stock, Kristin; Estrada, Marta F; Vidic, Suzana; Gjerde, Kjersti; Rudisch, Albin; Santo, Vítor E; Barbier, Michaël; Blom, Sami; Arundkar, Sharath C; Selvam, Irwin; Osswald, Annika; Stein, Yan; Gruenewald, Sylvia; Brito, Catarina; van Weerden, Wytske; Rotter, Varda; Boghaert, Erwin; Oren, Moshe; Sommergruber, Wolfgang; Chong, Yolanda; de Hoogt, Ronald; Graeser, Ralph

2016-07-01

Two-dimensional (2D) cell cultures growing on plastic do not recapitulate the three dimensional (3D) architecture and complexity of human tumors. More representative models are required for drug discovery and validation. Here, 2D culture and 3D mono- and stromal co-culture models of increasing complexity have been established and cross-comparisons made using three standard cell carcinoma lines: MCF7, LNCaP, NCI-H1437. Fluorescence-based growth curves, 3D image analysis, immunohistochemistry and treatment responses showed that end points differed according to cell type, stromal co-culture and culture format. The adaptable methodologies described here should guide the choice of appropriate simple and complex in vitro models.

Capturing tumor complexity in vitro: Comparative analysis of 2D and 3D tumor models for drug discovery

PubMed Central

Stock, Kristin; Estrada, Marta F.; Vidic, Suzana; Gjerde, Kjersti; Rudisch, Albin; Santo, Vítor E.; Barbier, Michaël; Blom, Sami; Arundkar, Sharath C.; Selvam, Irwin; Osswald, Annika; Stein, Yan; Gruenewald, Sylvia; Brito, Catarina; van Weerden, Wytske; Rotter, Varda; Boghaert, Erwin; Oren, Moshe; Sommergruber, Wolfgang; Chong, Yolanda; de Hoogt, Ronald; Graeser, Ralph

2016-01-01

Two-dimensional (2D) cell cultures growing on plastic do not recapitulate the three dimensional (3D) architecture and complexity of human tumors. More representative models are required for drug discovery and validation. Here, 2D culture and 3D mono- and stromal co-culture models of increasing complexity have been established and cross-comparisons made using three standard cell carcinoma lines: MCF7, LNCaP, NCI-H1437. Fluorescence-based growth curves, 3D image analysis, immunohistochemistry and treatment responses showed that end points differed according to cell type, stromal co-culture and culture format. The adaptable methodologies described here should guide the choice of appropriate simple and complex in vitro models. PMID:27364600

Theoretical studies of charge transfer and proton transfer complex formation between 3,5-dinitrobenzic acid and 1,2-dimethylimidazole

NASA Astrophysics Data System (ADS)

Afroz, Ziya; Faizan, Mohd.; Alam, Mohammad Jane; Ahmad, Shabbir; Ahmad, Afaq

2018-05-01

Natural atomic charge analysis and molecular electrostatic potential (MEP) surface analysis of hydrogen bonded charge transfer (HBCT) and proton transfer (PT) complex of 3,5-dinitrobenzoic acid (DNBA) and 1,2-dimethylimidazole (DMI) have been investigated by theoretical modelling using widely employed DFT/B3LYP/6-311G(d,p) level of theory. Along with this analysis, Hirshfeld surface study of the intermolecular interactions and associated 2D finger plot for reported PT complex between DNBA and DMI have been explored.

Fractional modeling of viscoelasticity in 3D cerebral arteries and aneurysms

NASA Astrophysics Data System (ADS)

Yu, Yue; Perdikaris, Paris; Karniadakis, George Em

2016-10-01

We develop efficient numerical methods for fractional order PDEs, and employ them to investigate viscoelastic constitutive laws for arterial wall mechanics. Recent simulations using one-dimensional models [1] have indicated that fractional order models may offer a more powerful alternative for modeling the arterial wall response, exhibiting reduced sensitivity to parametric uncertainties compared with the integer-calculus-based models. Here, we study three-dimensional (3D) fractional PDEs that naturally model the continuous relaxation properties of soft tissue, and for the first time employ them to simulate flow structure interactions for patient-specific brain aneurysms. To deal with the high memory requirements and in order to accelerate the numerical evaluation of hereditary integrals, we employ a fast convolution method [2] that reduces the memory cost to O (log ⁡ (N)) and the computational complexity to O (Nlog ⁡ (N)). Furthermore, we combine the fast convolution with high-order backward differentiation to achieve third-order time integration accuracy. We confirm that in 3D viscoelastic simulations, the integer order models strongly depends on the relaxation parameters, while the fractional order models are less sensitive. As an application to long-time simulations in complex geometries, we also apply the method to modeling fluid-structure interaction of a 3D patient-specific compliant cerebral artery with an aneurysm. Taken together, our findings demonstrate that fractional calculus can be employed effectively in modeling complex behavior of materials in realistic 3D time-dependent problems if properly designed efficient algorithms are employed to overcome the extra memory requirements and computational complexity associated with the non-local character of fractional derivatives.

Fractional modeling of viscoelasticity in 3D cerebral arteries and aneurysms

PubMed Central

Perdikaris, Paris; Karniadakis, George Em

2017-01-01

We develop efficient numerical methods for fractional order PDEs, and employ them to investigate viscoelastic constitutive laws for arterial wall mechanics. Recent simulations using one-dimensional models [1] have indicated that fractional order models may offer a more powerful alternative for modeling the arterial wall response, exhibiting reduced sensitivity to parametric uncertainties compared with the integer-calculus-based models. Here, we study three-dimensional (3D) fractional PDEs that naturally model the continuous relaxation properties of soft tissue, and for the first time employ them to simulate flow structure interactions for patient-specific brain aneurysms. To deal with the high memory requirements and in order to accelerate the numerical evaluation of hereditary integrals, we employ a fast convolution method [2] that reduces the memory cost to O(log(N)) and the computational complexity to O(N log(N)). Furthermore, we combine the fast convolution with high-order backward differentiation to achieve third-order time integration accuracy. We confirm that in 3D viscoelastic simulations, the integer order models strongly depends on the relaxation parameters, while the fractional order models are less sensitive. As an application to long-time simulations in complex geometries, we also apply the method to modeling fluid–structure interaction of a 3D patient-specific compliant cerebral artery with an aneurysm. Taken together, our findings demonstrate that fractional calculus can be employed effectively in modeling complex behavior of materials in realistic 3D time-dependent problems if properly designed efficient algorithms are employed to overcome the extra memory requirements and computational complexity associated with the non-local character of fractional derivatives. PMID:29104310

Research on complex 3D tree modeling based on L-system

NASA Astrophysics Data System (ADS)

Gang, Chen; Bin, Chen; Yuming, Liu; Hui, Li

2018-03-01

L-system as a fractal iterative system could simulate complex geometric patterns. Based on the field observation data of trees and knowledge of forestry experts, this paper extracted modeling constraint rules and obtained an L-system rules set. Using the self-developed L-system modeling software the L-system rule set was parsed to generate complex tree 3d models.The results showed that the geometrical modeling method based on l-system could be used to describe the morphological structure of complex trees and generate 3D tree models.

3D printed renal cancer models derived from MRI data: application in pre-surgical planning.

PubMed

Wake, Nicole; Rude, Temitope; Kang, Stella K; Stifelman, Michael D; Borin, James F; Sodickson, Daniel K; Huang, William C; Chandarana, Hersh

2017-05-01

To determine whether patient-specific 3D printed renal tumor models change pre-operative planning decisions made by urological surgeons in preparation for complex renal mass surgical procedures. From our ongoing IRB approved study on renal neoplasms, ten renal mass cases were retrospectively selected based on Nephrometry Score greater than 5 (range 6-10). A 3D post-contrast fat-suppressed gradient-echo T1-weighted sequence was used to generate 3D printed models. The cases were evaluated by three experienced urologic oncology surgeons in a randomized fashion using (1) imaging data on PACS alone and (2) 3D printed model in addition to the imaging data. A questionnaire regarding surgical approach and planning was administered. The presumed pre-operative approaches with and without the model were compared. Any change between the presumed approaches and the actual surgical intervention was recorded. There was a change in planned approach with the 3D printed model for all ten cases with the largest impact seen regarding decisions on transperitoneal or retroperitoneal approach and clamping, with changes seen in 30%-50% of cases. Mean parenchymal volume loss for the operated kidney was 21.4%. Volume losses >20% were associated with increased ischemia times and surgeons tended to report a different approach with the use of the 3D model compared to that with imaging alone in these cases. The 3D printed models helped increase confidence regarding the chosen operative procedure in all cases. Pre-operative physical 3D models created from MRI data may influence surgical planning for complex kidney cancer.

A mechanistic role of Helix 8 in GPCRs: Computational modeling of the dopamine D2 receptor interaction with the GIPC1-PDZ-domain.

PubMed

Sensoy, Ozge; Weinstein, Harel

2015-04-01

Helix-8 (Hx8) is a structurally conserved amphipathic helical motif in class-A GPCRs, adjacent to the C-terminal sequence that is responsible for PDZ-domain-recognition. The Hx8 segment in the dopamine D2 receptor (D2R) constitutes the C-terminal segment and we investigate its role in the function of D2R by studying the interaction with the PDZ-containing GIPC1 using homology models based on the X-ray structures of very closely related analogs: the D3R for the D2R model, and the PDZ domain of GIPC2 for GIPC1-PDZ. The mechanism of this interaction was investigated with all-atom unbiased molecular dynamics (MD) simulations that reveal the role of the membrane in maintaining the helical fold of Hx8, and with biased MD simulations to elucidate the energy drive for the interaction with the GIPC1-PDZ. We found that it becomes more favorable energetically for Hx8 to adopt the extended conformation observed in all PDZ-ligand complexes when it moves away from the membrane, and that C-terminus palmitoylation of D2R enhanced membrane penetration by the Hx8 backbone. De-palmitoylation enables Hx8 to move out into the aqueous environment for interaction with the PDZ domain. All-atom unbiased MD simulations of the full D2R-GIPC1-PDZ complex in sphingolipid/cholesterol membranes show that the D2R carboxyl C-terminus samples the region of the conserved GFGL motif located on the carboxylate-binding loop of the GIPC1-PDZ, and the entire complex distances itself from the membrane interface. Together, these results outline a likely mechanism of Hx8 involvement in the interaction of the GPCR with PDZ-domains in the course of signaling. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

A mechanistic role of Helix 8 in GPCRs: Computational modeling of the dopamine D2 receptor interaction with the GIPC1-PDZ-domain

PubMed Central

Sensoy, Ozge; Weinstein, Harel

2015-01-01

Helix-8 (Hx8) is a structurally conserved amphipathic helical motif in class-A GPCRs, adjacent to the C-terminal sequence that is responsible for PDZ-domain-recognition. The Hx8 segment in the dopamine D2 receptor (D2R) constitutes the C-terminal segment and we investigate its role in the function of D2R by studying the interaction with the PDZ-containing GIPC1 using homology models based on the X-ray structures of very closely related analogs: the D3R for the D2R model, and the PDZ domain of GIPC2 for GIPC1-PDZ. The mechanism of this interaction was investigated with all-atom unbiased molecular dynamics (MD) simulations that reveal the role of the membrane in maintaining the helical fold of Hx8, and with biased MD simulations to elucidate the energy drive for the interaction with the GIPC1-PDZ. We found that it becomes more favorable energetically for Hx8 to adopt the extended conformation observed in all PDZ-ligand complexes when it moves away from the membrane, and that C-terminus palmitoylation of D2R enhanced membrane penetration by the Hx8 backbone. De-palmitoylation enables Hx8 to move out into the aqueous environment for interaction with the PDZ domain. All-atom unbiased MD simulations of the full D2R-GIPC1 complex in sphingolipid/cholesterol membranes shows that the D2R carboxyl C-terminus samples the region of the conserved GFGL motif located on the carboxylate-binding loop of the GIPC1-PDZ, and the entire complex distances itself from the membrane interface. Together, these results outline a likely mechanism of Hx8 involvement in the interaction of the GPCR with PDZ-domains in the course of signaling. PMID:25592838

A mechanistic role of Helix 8 in GPCRs: Computational modeling of the dopamine D2 receptor interaction with the GIPC1–PDZ-domain

DOE PAGES

Sensoy, Ozge; Weinstein, Harel

2015-01-12

Helix-8 (Hx8) is a structurally conserved amphipathic helical motif in class-A GPCRs, adjacent to the C-terminal sequence that is responsible for PDZ-domain-recognition. The Hx8 segment in the dopamine D2 receptor (D2R) constitutes the C-terminal segment and we investigate its role in the function of D2R by studying the interaction with the PDZ-containing GIPC1 using homology models based on the X-ray structures of very closely related analogs: the D3R for the D2R model, and the PDZ domain of GIPC2 for GIPC1–PDZ. The mechanism of this interaction was investigated with all-atom unbiased molecular dynamics (MD) simulations that reveal the role of themore » membrane in maintaining the helical fold of Hx8, and with biased MD simulations to elucidate the energy drive for the interaction with the GIPC1–PDZ. We found that it becomes more favorable energetically for Hx8 to adopt the extended conformation observed in all PDZ–ligand complexes when it moves away from the membrane, and that C-terminus palmitoylation of D2R enhanced membrane penetration by the Hx8 backbone. De-palmitoylation enables Hx8 to move out into the aqueous environment for interaction with the PDZ domain. All-atom unbiased MD simulations of the full D2R–GIPC1-PDZ complex in sphingolipid/cholesterol membranes show that the D2R carboxyl C-terminus samples the region of the conserved GFGL motif located on the carboxylate-binding loop of the GIPC1–PDZ, and the entire complex distances itself from the membrane interface. Altogether, these results outline a likely mechanism of Hx8 involvement in the interaction of the GPCR with PDZ-domains in the course of signaling.« less

Blast Fragmentation Modeling and Analysis

DTIC Science & Technology

2010-10-31

weapons device containing a multiphase blast explosive (MBX). 1. INTRODUCTION The ARL Survivability Lethality and Analysis Directorate (SLAD) is...velocity. In order to simulate the highly complex phenomenon, the exploding cylinder is modeled with the hydrodynamics code ALE3D , an arbitrary...Lagrangian-Eulerian multiphysics code, developed at Lawrence Livermore National Laboratory. ALE3D includes physical properties, constitutive models for

Promising applications in drug delivery systems of a novel β-cyclodextrin derivative obtained by green synthesis.

PubMed

García, Agustina; Leonardi, Darío; Lamas, María C

2016-01-15

An efficient and green method has been developed for the synthesis of succinyl-β-cyclodextrin in aqueous media obtaining very good yield. Acidic groups have been introduced in the synthesized carrier molecule to improve the guest-host affinity. To evaluate the suitability of the novel excipient focused to develop oral dosage forms, albendazole, a BSC class II compound, was chosen as a model drug. The β-cyclodextrin derivative and the inclusion complex were thoroughly characterized in solution and solid state by phase solubility studies, FT-IR spectroscopy, SEM, XRD, ESI-MS, DSC, 1D (1)H NMR, 1D (13)C NMR, selective 1D TOCSY, 2D COSY, 2D HSQC, 2D HMBC and ROESY NMR spectroscopy. Phase solubility studies indicated that both of them β-cyclodextrin and succinyl-β-cyclodextrin formed 1:1 inclusion complexes with albendazole, and the stability constants were 68M(-1) (β-cyclodextrin), 437M(-1) (succinyl-β-cyclodextrin), respectively. Water solubility and dissolution rate of albendazole were significantly improved in complex forms. Thus, the succinyl-β-cyclodextrin derivative could be a promising excipient to design oral dosage forms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Constructing high-accuracy intermolecular potential energy surface with multi-dimension Morse/Long-Range model

NASA Astrophysics Data System (ADS)

Zhai, Yu; Li, Hui; Le Roy, Robert J.

2018-04-01

Spectroscopically accurate Potential Energy Surfaces (PESs) are fundamental for explaining and making predictions of the infrared and microwave spectra of van der Waals (vdW) complexes, and the model used for the potential energy function is critically important for providing accurate, robust and portable analytical PESs. The Morse/Long-Range (MLR) model has proved to be one of the most general, flexible and accurate one-dimensional (1D) model potentials, as it has physically meaningful parameters, is flexible, smooth and differentiable everywhere, to all orders and extrapolates sensibly at both long and short ranges. The Multi-Dimensional Morse/Long-Range (mdMLR) potential energy model described herein is based on that 1D MLR model, and has proved to be effective and accurate in the potentiology of various types of vdW complexes. In this paper, we review the current status of development of the mdMLR model and its application to vdW complexes. The future of the mdMLR model is also discussed. This review can serve as a tutorial for the construction of an mdMLR PES.

^1H NMR studies of the diamagnetic gallium (III) and paramagnetic iron (III) complexes of a chiral macrobicyclic ligand of bicapped tris (binaphtol) type

NASA Astrophysics Data System (ADS)

Baret, P.; Beaujolais, V.; Bougault, C.; Gaude, D.; Pierre, J.-L.

1998-01-01

^1H NMR studies of the diamagnetic gallium (III) and paramagnetic iron (III) complexes of a chiral macrobicyclic ligand of bicapped tris (binaphtol) type are described. The study of the gallium complex emphasizes: (i) that the inversion of the octahedral center is not observed and: (ii) the absence of exchange between free ligand and complex, at room temperature. In the case of the iron complex, assignments of the hyperfine shifted resolved resonances are achieved, based on temperature-behavior studies, which evidence the D3 symmetry of the complex. These assignments are in complete agreement with measured T1 values and proton-to-iron distances obtained from molecular modelling. Les complexes du gallium (III) et du fer (III) d'un ligand macrobicyclique chiral impliquant trois sous-unités de type binaphtol sont étudiés en RMN du proton en solution méthanolique. L'étude du complexe (diamagnétique) du gallium permet de montrer que le complexe : (i) ne subit pas d'inversion de la configuration (Δ/Λ) du site octaédrique et : (ii) qu'il n'y a pas d'échange entre ligand libre et complexe à la température ambiante. L'évolution du spectre du complexe paramagnétique du fer avec la température permet une attribution des protons du ligand et met en évidence la symétrie D3 du complexe. Une bonne corrélation est obtenue entre la distance fer-proton (donnée par la modélisation moléculaire) et le T1 du proton considéré.

Enhanced LOD Concepts for Virtual 3d City Models

NASA Astrophysics Data System (ADS)

Benner, J.; Geiger, A.; Gröger, G.; Häfele, K.-H.; Löwner, M.-O.

2013-09-01

Virtual 3D city models contain digital three dimensional representations of city objects like buildings, streets or technical infrastructure. Because size and complexity of these models continuously grow, a Level of Detail (LoD) concept effectively supporting the partitioning of a complete model into alternative models of different complexity and providing metadata, addressing informational content, complexity and quality of each alternative model is indispensable. After a short overview on various LoD concepts, this paper discusses the existing LoD concept of the CityGML standard for 3D city models and identifies a number of deficits. Based on this analysis, an alternative concept is developed and illustrated with several examples. It differentiates between first, a Geometric Level of Detail (GLoD) and a Semantic Level of Detail (SLoD), and second between the interior building and its exterior shell. Finally, a possible implementation of the new concept is demonstrated by means of an UML model.

Coupling HYDRUS-1D Code with PA-DDS Algorithms for Inverse Calibration

NASA Astrophysics Data System (ADS)

Wang, Xiang; Asadzadeh, Masoud; Holländer, Hartmut

2017-04-01

Numerical modelling requires calibration to predict future stages. A standard method for calibration is inverse calibration where generally multi-objective optimization algorithms are used to find a solution, e.g. to find an optimal solution of the van Genuchten Mualem (VGM) parameters to predict water fluxes in the vadose zone. We coupled HYDRUS-1D with PA-DDS to add a new, robust function for inverse calibration to the model. The PA-DDS method is a recently developed multi-objective optimization algorithm, which combines Dynamically Dimensioned Search (DDS) and Pareto Archived Evolution Strategy (PAES). The results were compared to a standard method (Marquardt-Levenberg method) implemented in HYDRUS-1D. Calibration performance is evaluated using observed and simulated soil moisture at two soil layers in the Southern Abbotsford, British Columbia, Canada in the terms of the root mean squared error (RMSE) and the Nash-Sutcliffe Efficiency (NSE). Results showed low RMSE values of 0.014 and 0.017 and strong NSE values of 0.961 and 0.939. Compared to the results by the Marquardt-Levenberg method, we received better calibration results for deeper located soil sensors. However, VGM parameters were similar comparing with previous studies. Both methods are equally computational efficient. We claim that a direct implementation of PA-DDS into HYDRUS-1D should reduce the computation effort further. This, the PA-DDS method is efficient for calibrating recharge for complex vadose zone modelling with multiple soil layer and can be a potential tool for calibration of heat and solute transport. Future work should focus on the effectiveness of PA-DDS for calibrating more complex versions of the model with complex vadose zone settings, with more soil layers, and against measured heat and solute transport. Keywords: Recharge, Calibration, HYDRUS-1D, Multi-objective Optimization

Drop formation, pinch-off dynamics and liquid transfer of simple and complex fluids

NASA Astrophysics Data System (ADS)

Dinic, Jelena; Sharma, Vivek

Liquid transfer and drop formation processes underlying jetting, spraying, coating, and printing - inkjet, screen, roller-coating, gravure, nanoimprint hot embossing, 3D - often involve formation of unstable columnar necks. Capillary-driven thinning of such necks and their pinchoff dynamics are determined by a complex interplay of inertial, viscous and capillary stresses for simple, Newtonian fluids. Micro-structural changes in response to extensional flow field that arises within the thinning neck give rise to additional viscoelastic stresses in complex, non- Newtonian fluids. Using FLOW-3D, we simulate flows realized in prototypical geometries (dripping and liquid bridge stretched between two parallel plates) used for studying pinch-off dynamics and influence of microstructure and viscoelasticity. In contrast with often-used 1D or 2D models, FLOW-3D allows a robust evaluation of the magnitude of the underlying stresses and extensional flow field (both uniformity and magnitude). We find that the simulated radius evolution profiles match the pinch-off dynamics that are experimentally-observed and theoretically-predicted for model Newtonian fluids and complex fluids.

Investigating the Performance of One- and Two-dimensional Flood Models in a Channelized River Network: A Case Study of the Obion River System

NASA Astrophysics Data System (ADS)

Kalyanapu, A. J.; Dullo, T. T.; Thornton, J. C.; Auld, L. A.

2015-12-01

Obion River, is located in the northwestern Tennessee region, and discharges into the Mississippi River. In the past, the river system was largely channelized for agricultural purposes that resulted in increased erosion, loss of wildlife habitat and downstream flood risks. These impacts are now being slowly reversed mainly due to wetland restoration. The river system is characterized by a large network of "loops" around the main channels that hold water either from excess flows or due to flow diversions. Without data on each individual channel, levee, canal, or pond it is not known where the water flows from or to. In some segments along the river, the natural channel has been altered and rerouted by the farmers for their irrigation purposes. Satellite imagery can aid in identifying these features, but its spatial coverage is temporally sparse. All the alterations that have been done to the watershed make it difficult to develop hydraulic models, which could predict flooding and droughts. This is especially true when building one-dimensional (1D) hydraulic models compared to two-dimensional (2D) models, as the former cannot adequately simulate lateral flows in the floodplain and in complex terrains. The objective of this study therefore is to study the performance of 1D and 2D flood models in this complex river system, evaluate the limitations of 1D models and highlight the advantages of 2D models. The study presents the application of HEC-RAS and HEC-2D models developed by the Hydrologic Engineering Center (HEC), a division of the US Army Corps of Engineers. The broader impacts of this study is the development of best practices for developing flood models in channelized river systems and in agricultural watersheds.

Three-dimensional computer simulation of radiostereometric analysis (RSA) in distal radius fractures.

PubMed

Madanat, Rami; Moritz, Niko; Aro, Hannu T

2007-01-01

Physical phantom models have conventionally been used to determine the accuracy and precision of radiostereometric analysis (RSA) in various orthopaedic applications. Using a phantom model of a fracture of the distal radius it has previously been shown that RSA is a highly accurate and precise method for measuring both translation and rotation in three-dimensions (3-D). The main shortcoming of a physical phantom model is its inability to mimic complex 3-D motion. The goal of this study was to create a realistic computer model for preoperative planning of RSA studies and to test the accuracy of RSA in measuring complex movements in fractures of the distal radius using this new model. The 3-D computer model was created from a set of tomographic scans. The simulation of the radiographic imaging was performed using ray-tracing software (POV-Ray). RSA measurements were performed according to standard protocol. Using a two-part fracture model (AO/ASIF type A2), it was found that for simple movements in one axis, translations in the range of 25microm-2mm could be measured with an accuracy of +/-2microm. Rotations ranging from 16 degrees to 2 degrees could be measured with an accuracy of +/-0.015 degrees . Using a three-part fracture model the corresponding values of accuracy were found to be +/-4microm and +/-0.031 degrees for translation and rotation, respectively. For complex 3-D motion in a three-part fracture model (AO/ASIF type C1) the accuracy was +/-6microm for translation and +/-0.120 degrees for rotation. The use of 3-D computer modelling can provide a method for preoperative planning of RSA studies in complex fractures of the distal radius and in other clinical situations in which the RSA method is applicable.

Structure, stability, and thermodynamics of lamellar DNA-lipid complexes.

PubMed Central

Harries, D; May, S; Gelbart, W M; Ben-Shaul, A

1998-01-01

We develop a statistical thermodynamic model for the phase evolution of DNA-cationic lipid complexes in aqueous solution, as a function of the ratios of charged to neutral lipid and charged lipid to DNA. The complexes consist of parallel strands of DNA intercalated in the water layers of lamellar stacks of mixed lipid bilayers, as determined by recent synchrotron x-ray measurements. Elastic deformations of the DNA and the lipid bilayers are neglected, but DNA-induced spatial inhomogeneities in the bilayer charge densities are included. The relevant nonlinear Poisson-Boltzmann equation is solved numerically, including self-consistent treatment of the boundary conditions at the polarized membrane surfaces. For a wide range of lipid compositions, the phase evolution is characterized by three regions of lipid to DNA charge ratio, rho: 1) for low rho, the complexes coexist with excess DNA, and the DNA-DNA spacing in the complex, d, is constant; 2) for intermediate rho, including the isoelectric point rho = 1, all of the lipid and DNA in solution is incorporated into the complex, whose inter-DNA distance d increases linearly with rho; and 3) for high rho, the complexes coexist with excess liposomes (whose lipid composition is different from that in the complex), and their spacing d is nearly, but not completely, independent of rho. These results can be understood in terms of a simple charging model that reflects the competition between counterion entropy and inter-DNA (rho < 1) and interbilayer (rho > 1) repulsions. Finally, our approach and conclusions are compared with theoretical work by others, and with relevant experiments. PMID:9649376

Magnetic anisotropy in nickel complexes as determined by combined magnetic susceptibility/magnetization/theoretical studies

NASA Astrophysics Data System (ADS)

Mašlejová, Anna; Boča, Roman; Dlháň, L.'ubor; Herchel, Radovan

2004-05-01

The zero-field splitting in nickel(II) complexes was modeled by considering all relevant operators (electron repulsion, crystal-field, spin-orbit coupling, orbital-Zeeman, and spin-Zeeman) in the complete basis set spanned by d n-atomic terms. D-values between weak and strong crystal field limits were evaluated from the crystal-field multiplets as well as using the spin Hamiltonian formalism. Importance of the anisotropic orbital reduction factors is discussed and exemplified by D/hc=-22 cm-1 as subtracted from magnetic data for [Ni(imidazole) 4(acetate) 2] complex.

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

Wang, Yazhen; Musser, Sarah K.; Saleh, Sam

1,N{sup 2}-Propanodeoxyguanosine (PdG) is a stable structural analogue for the 3-(2'-deoxy-{beta}-d-erythro-pentofuranosyl)pyrimido[1,2-?]purin-10(3H)-one (M{sub 1}dG) adduct derived from exposure of DNA to base propenals and to malondialdehyde. The structures of ternary polymerase-DNA-dNTP complexes for three template-primer DNA sequences were determined, with the Y-family Sulfolobus solfataricus DNA polymerase IV (Dpo4), at resolutions between 2.4 and 2.7 {angstrom}. Three template 18-mer-primer 13-mer sequences, 5'-d(TCACXAAATCCTTCCCCC)-3'{center_dot}5'-d(GGGGGAAGGATTT)-3' (template I), 5'-d(TCACXGAATCCTTCCCCC)-3'{center_dot}5'-d(GGGGGAAGGATTC)-3' (template II), and 5'-d(TCATXGAATCCTTCCCCC)-3'{center_dot}5'-d(GGGGGAAGGATTC)-3' (template III), where X is PdG, were analyzed. With templates I and II, diffracting ternary complexes including dGTP were obtained. The dGTP did not pair with PdG, but instead with the 5'-neighboring templatemore » dC, utilizing Watson-Crick geometry. Replication bypass experiments with the template-primer 5?-TCACXAAATCCTTACGAGCATCGCCCCC-3'{center_dot}5'-GGGGGCGATGCTCGTAAGGATTT-3', where X is PdG, which includes PdG in the 5'-CXA-3' template sequence as in template I, showed that the Dpo4 polymerase inserted dGTP and dATP when challenged by the PdG adduct. For template III, in which the template sequence was 5'-TXG-3', a diffracting ternary complex including dATP was obtained. The dATP did not pair with PdG, but instead with the 5'-neighboring T, utilizing Watson-Crick geometry. Thus, all three ternary complexes were of the 'type II' structure described for ternary complexes with native DNA [Ling, H., Boudsocq, F., Woodgate, R., and Yang, W. (2001) Cell 107, 91--102]. The PdG adduct remained in the anti conformation about the glycosyl bond in each of these threee ternary complexes. These results provide insight into how -1 frameshift mutations might be generated for the PdG adduct, a structural model for the exocylic M{sub 1}dG adduct formed by malondialdehyde.« less

Finding Furfural Hydrogenation Catalysts via Predictive Modelling

PubMed Central

Strassberger, Zea; Mooijman, Maurice; Ruijter, Eelco; Alberts, Albert H; Maldonado, Ana G; Orru, Romano V A; Rothenberg, Gadi

2010-01-01

Abstract We combine multicomponent reactions, catalytic performance studies and predictive modelling to find transfer hydrogenation catalysts. An initial set of 18 ruthenium-carbene complexes were synthesized and screened in the transfer hydrogenation of furfural to furfurol with isopropyl alcohol complexes gave varied yields, from 62% up to >99.9%, with no obvious structure/activity correlations. Control experiments proved that the carbene ligand remains coordinated to the ruthenium centre throughout the reaction. Deuterium-labelling studies showed a secondary isotope effect (kH:kD=1.5). Further mechanistic studies showed that this transfer hydrogenation follows the so-called monohydride pathway. Using these data, we built a predictive model for 13 of the catalysts, based on 2D and 3D molecular descriptors. We tested and validated the model using the remaining five catalysts (cross-validation, R2=0.913). Then, with this model, the conversion and selectivity were predicted for four completely new ruthenium-carbene complexes. These four catalysts were then synthesized and tested. The results were within 3% of the model’s predictions, demonstrating the validity and value of predictive modelling in catalyst optimization. PMID:23193388

3-D Inhomogeous Radiative Transfer Model using a Planar-stratified Forward RT Model and Horizontal Perturbation Series

NASA Astrophysics Data System (ADS)

Zhang, K.; Gasiewski, A. J.

2017-12-01

A horizontally inhomogeneous unified microwave radiative transfer (HI-UMRT) model based upon a nonspherical hydrometeor scattering model is being developed at the University of Colorado at Boulder to facilitate forward radiative simulations for 3-dimensionally inhomogeneous clouds in severe weather. The HI-UMRT 3-D analytical solution is based on incorporating a planar-stratified 1-D UMRT algorithm within a horizontally inhomogeneous iterative perturbation scheme. Single-scattering parameters are computed using the Discrete Dipole Scattering (DDSCAT v7.3) program for hundreds of carefully selected nonspherical complex frozen hydrometeors from the NASA/GSFC DDSCAT database. The required analytic factorization symmetry of transition matrix in a normalized RT equation was analytically proved and validated numerically using the DDSCAT-based full Stokes matrix of randomly oriented hydrometeors. The HI-UMRT model thus inherits the properties of unconditional numerical stability, efficiency, and accuracy from the UMRT algorithm and provides a practical 3-D two-Stokes parameter radiance solution with Jacobian to be used within microwave retrievals and data assimilation schemes. In addition, a fast forward radar reflectivity operator with Jacobian based on DDSCAT backscatter efficiency computed for large hydrometeors is incorporated into the HI-UMRT model to provide applicability to active radar sensors. The HI-UMRT will be validated strategically at two levels: 1) intercomparison of brightness temperature (Tb) results with those of several 1-D and 3-D RT models, including UMRT, CRTM and Monte Carlo models, 2) intercomparison of Tb with observed data from combined passive and active spaceborne sensors (e.g. GPM GMI and DPR). The precise expression for determining the required number of 3-D iterations to achieve an error bound on the perturbation solution will be developed to facilitate the numerical verification of the HI-UMRT code complexity and computation performance.

Membrane Interaction of Antimicrobial Peptides Using E. coli Lipid Extract as Model Bacterial Cell Membranes and SFG Spectroscopy

PubMed Central

Soblosky, Lauren; Ramamoorthy, Ayyalusamy; Chen, Zhan

2015-01-01

Supported lipid bilayers are used as a convenient model cell membrane system to study biologically important molecule-lipid interactions in situ. However, the lipid bilayer models are often simple and the acquired results with these models may not provide all pertinent information related to a real cell membrane. In this work, we use sum frequency generation (SFG) vibrational spectroscopy to study molecular-level interactions between the antimicrobial peptides (AMPs) MSI-594, ovispirin-1 G18, magainin 2 and a simple 1,2-dipalmitoyl-d62-sn-glycero-3-phosphoglycerol (dDPPG)-1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) bilayer. We compared such interactions to those between the AMPs and a more complex dDPPG/E. coli polar lipid extract bilayer. We show that to fully understand more complex aspects of peptide-bilayer interaction, such as interaction kinetics, a heterogeneous lipid composition is required, such as the E. coli polar lipid extract. The discrepancy in peptide-bilayer interaction is likely due in part to the difference in bilayer charge between the two systems since highly negative charged lipids can promote more favorable electrostatic interactions between the peptide and lipid bilayer. Results presented in this paper indicate that more complex model bilayers are needed to accurately analyze peptide-cell membrane interactions and demonstrates the importance of using an appropriate lipid composition to study AMP interaction properties. PMID:25707312

The application of CFD to the modelling of fires in complex geometries

NASA Astrophysics Data System (ADS)

Burns, A. D.; Clarke, D. S.; Guilbert, P.; Jones, I. P.; Simcox, S.; Wilkes, N. S.

The application of Computational Fluid Dynamics (CFD) to industrial safety is a challenging activity. In particular it involves the interaction of several different physical processes, including turbulence, combustion, radiation, buoyancy, compressible flow and shock waves in complex three-dimensional geometries. In addition, there may be multi-phase effects arising, for example, from sprinkler systems for extinguishing fires. The FLOW3D software (1-3) from Computational Fluid Dynamics Services (CFDS) is in widespread use in industrial safety problems, both within AEA Technology, and also by CFDS's commercial customers, for example references (4-13). This paper discusses some other applications of FLOW3D to safety problems. These applications illustrate the coupling of the gas flows with radiation models and combustion models, particularly for complex geometries where simpler radiation models are not applicable.

Synchrotron Protein Footprinting Supports Substrate Translocation by ClpA via ATP-Induced Movements of the D2 Loop

PubMed Central

Bohon, Jen; Jennings, Laura D.; Phillips, Christine M.; Licht, Stuart; Chance, Mark R.

2010-01-01

SUMMARY Synchrotron x-ray protein footprinting is used to study structural changes upon formation of the ClpA hexamer. Comparative solvent accessibilities between ClpA monomer and ClpA hexamer samples are in agreement throughout most of the sequence with calculations based on two previously proposed hexameric models. The data differ substantially from the proposed models in two parts of the structure: the D1 sensor 1 domain and the D2 loop region. The results suggest that these two regions can access alternate conformations in which their solvent protection is greater than in the structural models based on crystallographic data. In combination with previously reported structural data, the footprinting data provide support for a revised model in which the D2 loop contacts the D1 sensor 1 domain in the ATP-bound form of the complex. These data provide the first direct experimental support for the nucleotide-dependent D2 loop conformational change previously proposed to mediate substrate translocation. PMID:18682217

Accuracy of 1D microvascular flow models in the limit of low Reynolds numbers.

PubMed

Pindera, Maciej Z; Ding, Hui; Athavale, Mahesh M; Chen, Zhijian

2009-05-01

We describe results of numerical simulations of steady flows in tubes with branch bifurcations using fully 3D and reduced 1D geometries. The intent is to delineate the range of validity of reduced models used for simulations of flows in microcapillary networks, as a function of the flow Reynolds number Re. Results from model problems indicate that for Re less than 1 and possibly as high as 10, vasculatures may be represented by strictly 1D Poiseuille flow geometries with flow variation in the axial dimensions only. In that range flow rate predictions in the different branches generated by 1D and 3D models differ by a constant factor, independent of Re. When the cross-sectional areas of the branches are constant these differences are generally small and appear to stem from an uncertainty of how the individual branch lengths are defined. This uncertainty can be accounted for by a simple geometrical correction. For non-constant cross-sections the differences can be much more significant. If additional corrections for the presence of branch junctions and flow area variations are not taken into account in 1D models of complex vasculatures, the resultant flow predictions should be interpreted with caution.

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

Sensoy, Ozge; Weinstein, Harel

Helix-8 (Hx8) is a structurally conserved amphipathic helical motif in class-A GPCRs, adjacent to the C-terminal sequence that is responsible for PDZ-domain-recognition. The Hx8 segment in the dopamine D2 receptor (D2R) constitutes the C-terminal segment and we investigate its role in the function of D2R by studying the interaction with the PDZ-containing GIPC1 using homology models based on the X-ray structures of very closely related analogs: the D3R for the D2R model, and the PDZ domain of GIPC2 for GIPC1–PDZ. The mechanism of this interaction was investigated with all-atom unbiased molecular dynamics (MD) simulations that reveal the role of themore » membrane in maintaining the helical fold of Hx8, and with biased MD simulations to elucidate the energy drive for the interaction with the GIPC1–PDZ. We found that it becomes more favorable energetically for Hx8 to adopt the extended conformation observed in all PDZ–ligand complexes when it moves away from the membrane, and that C-terminus palmitoylation of D2R enhanced membrane penetration by the Hx8 backbone. De-palmitoylation enables Hx8 to move out into the aqueous environment for interaction with the PDZ domain. All-atom unbiased MD simulations of the full D2R–GIPC1-PDZ complex in sphingolipid/cholesterol membranes show that the D2R carboxyl C-terminus samples the region of the conserved GFGL motif located on the carboxylate-binding loop of the GIPC1–PDZ, and the entire complex distances itself from the membrane interface. Altogether, these results outline a likely mechanism of Hx8 involvement in the interaction of the GPCR with PDZ-domains in the course of signaling.« less

Heterogeneous strain and composite P-T paths: the key for unravelling complex tectonic histories in polymetamorphic high-grade terrains

NASA Astrophysics Data System (ADS)

van Reenen, Dirk D.; Smit, C. Andre

2010-05-01

Leonid Perchuk calculated the first P-T paths for eclogites almost 40 years ago [1] and since then he has shown that P-T paths if correctly constructed, represent an accurate record of the thermal and dynamic evolution of high-grade metamorphic complexes [2]. This implies that P-T paths might serve as the basis for geodynamic models for the formation and exhumation of such complexes from the lower crustal levels [2]. His continued research in the Limpopo Complex of southern Africa also played an important role in the next direction in the study of complex high-grade polymetamorphic complexes. This new direction involves the link between composite (kinked) P-T paths [5; 6; 8] and the critical role of heterogeneous strain in the development and preservation of distinct granulite facies events at the regional, outcrop, hand specimen, and thin section scales [7; 9; 10]. Heterogeneous deformation that operated on the thin section scale allowed the construction of kinked P-T paths from single thin sections [5; 6; 9] and the integration of the P-T data with structural and isotopic geochronology [7; 9; 10]. D-P-T-t paths thus constructed not only allow the nature of polymetamorphism in the Limpopo Complex of southern Africa to be established, but also assisted in the construction of tectonic models for the evolution of this complex high-grade polymetamorphic complex. This complex evolution is demonstrated by the configuration of a kinked P-T path (5; 9) that reflects the following distinct stages of the multi-cycle D-P-T-t evolution of the Central Zone: (i) the earliest DC1 path reflects the emplacement before ~2.63Ga of the Limpopo Complex at the crustal level of ~20km. The DC1 stage of the D1/M1 exhumation event was accompanied by the formation of early D2A isoclinal folds; (ii) The DC2 stage of the D1/M1 exhumation event reflects the emplacement before ~2.61Ga of the rocks at the crustal level of ~15km. The DC2 stage was accompanied by the formation of major D2B sheath folds; (iii) the high-grade rocks resided and cooled at this crustal level in the Central Zone of the Limpopo Complex for more than 600Ma before the rocks were again reheated at ~2.02Ga during a superimposed D2/M2 high-grade event. This event is reflected by an isobaric-heating (IC) P-T path that resulted in the widespread formation of polymetamorphic granulites; (iv) the IC path was followed a DC3 P-T path that reflects the final exhumation of the rocks to the upper crustal level during the D2/M2 event. High-grade D3A shear zones controlled the final exhumation of the rocks. Isobaric heating (IC) thus links Pmin (D1/M1) to Pmax (D2/M2) that resulted in a kinked configuration of the DC1/2=>IC=>DC3 P-T path. The end of the high-grade tectono-metamorphic event is signified by the development at ~2.01Ga of completely undeformed melt patches that destroy the D2B and D3A gneissic fabric of the rocks in which they are developed. Reactivation of SW-NE-trending high-grade D3A shear zones at ~1.9Ga resulted in the formation of upper crustal mylonitic shear zones that define the present belt-like geometry of the SW-NE trending Limpopo Complex. The successful link of composite (kinked) P-T paths with structural (D) and geochronological (t) data t formed the basis for the construction of D-P-T-t diagrams that demonstrate the polymetamorphic evolution of the Limpopo Complex as the result of superimposed Neoarchaean and Paleoproterozoic high-grade events. References: [1] Perchuk L.L. Physics of the Earth and Planetary Interiors, 1976. 13, 232-239. [2] Perchuk L.L. (1989) Geol. Soc. London. Special Publication. 2(20). 275-291. [3] Roering, C., Van Reenen, D.D., Smit, C.A., Barton, J.M. jr., de Beer, J.H., de Wit, M.J., Stettler, E.H., van Schalkwyk., J.F., Stevens, G., and Pretorius, S. 1992. Precambrian Research, 55, 539-552. [4] Gerya, T.V., Perchuk, L.L., Van Reenen, D.D., and Smit, C.A. 2000. J. Geodynamics, 30, 17-35. [5] Perchuk L.L. (2005) Dokl. Earth Sciences. 401. 311-314. [6] Perchuk, L.L., Gerya, T.V., Van Reenen, D.D., and Smit, C.A. 2006. Petrology, v. 14, no. 2, 131-167. [7] Mahan, K. H., Goncalves, P., Flowers, R. M., Williams, M. L., and Hoffman-Setka, D., 2008. Journal of Metamorphic Geology, DOI:10.1111/j.1525-1314. [8] Perchuk, L. L., van Reenen, D. D., Varlamov, D. A., van Kal, S. M., Tabatabaeimanesh, S. M., and Boshoff, R., 2008. Lithos, v. 103, p. 70-105. [9] Perchuk, L.L. and Van Reenen, D.D., 2008. Lithos, 106, 403-410. [10]. Van Reenen, D. D., Boshoff, R., Smit, C. A., Perchuk, L.L., Kramers, J. D.,McCourt, S. M., and Armstrong, R. A., 2008. Gondwana Research, v.14, p. 644-662.

Coupling MAST-1D, a sediment routing model for channel-floodplain complexes, with channel migration relationships to predict reach-averaged river morphodynamics. Preliminary results

NASA Astrophysics Data System (ADS)

Viparelli, E.; Eke, E. C.; Lauer, J. W.

2017-12-01

Sediment exchange between the channel and floodplain can occur via meander migration, overbank deposition or erosion, and changes in channel geometry. Depending on channel and floodplain history, floodplains can act either as sources or sinks of bed material and/or wash load. Here we present preliminary modeling results that explicitly account for the feedbacks between the changes in floodplain geometry and sediment size distribution and the changes in channel geometry and migration. These results are obtained by coupling the Morphodynamics And Sediment Tracers in 1D (MAST-1D) program with the results of meander migration studies linking the bankfull flow depth and mean velocity to channel migration, sinuosity and channel geometry. MAST-1D is a numerical model built to describe grain size specific transport of sediment and tracers and the long-term - i.e. decadal and longer - evolution of channel floodplain complexes. MAST-1D differs from other 1D numerical models because it allows for 1) uneven exchange of sediment and tracers between the river channel and the floodplain, 2) temporal changes in channel geometry, bed elevation and floodplain thickness, which result in changes in the channel hydraulic capacity, and 3) temporal changes of size distribution and tracer content in the floodplain, in the load and in the underlying substrate. Under conditions of constant base level, water and sediment supply, the system evolves toward a steady state wherein the amount of sediment deposited through point bar deposition and overbank sedimentation is balanced by the erosion of sediment from the floodplain through lateral migration. The current formulation couples MAST-1D with empirical channel migration relationships that link bankfull flow depth and mean velocity to channel migration, sinuosity and channel geometry. Future development of this preliminary work will involve a fully coupled MAST-1D model with a standard meander migration model that will allow for the building of floodplain stratigraphy and tracking of the position of the meandering channel in space and time.

Ibuprofen-in-cyclodextrin-in-W/O/W emulsion - Improving the initial and long-term encapsulation efficiency of a model active ingredient.

PubMed

Hattrem, Magnus N; Kristiansen, Kåre A; Aachmann, Finn L; Dille, Morten J; Draget, Kurt I

2015-06-20

A challenge in formulating water-in-oil-in-water (W/O/W) emulsions is the uncontrolled release of the encapsulated compound prior to application. Pharmaceuticals and nutraceuticals usually have amphipathic nature, which may contribute to leakage of the active ingredient. In the present study, cyclodextrins (CyDs) were used to impart a change in the relative polarity and size of a model compound (ibuprofen) by the formation of inclusion complexes. Various inclusion complexes (2-hydroxypropyl (HP)-β-CyD-, α-CyD- and γ-CyD-ibuprofen) were prepared and presented within W/O/W emulsions, and the initial and long-term encapsulation efficiency was investigated. HP-β-CyD-ibuprofen provided the highest encapsulation of ibuprofen in comparison to a W/O/W emulsion with unassociated ibuprofen confined within the inner water phase, with a four-fold increase in the encapsulation efficiency. An improved, although lower, encapsulation efficiency was obtained for the inclusion complex γ-CyD-ibuprofen in comparison to HP-β-CyD-ibuprofen, whereas α-CyD-ibuprofen had a similar encapsulation efficiency to that of unassociated ibuprofen. The lower encapsulation efficiency of ibuprofen in combination with α-CyD and γ-CyD was attributed to a lower association constant for the γ-CyD-ibuprofen inclusion complex and the ability of α-CyD to form inclusion complexes with fatty acids. For the W/O/W emulsion prepared with HP-β-CyD-ibuprofen, the highest encapsulation of ibuprofen was obtained at hyper- and iso-osmotic conditions and by using an excess molar ratio of CyD to ibuprofen. In the last part of the study, it was suggested that the chemical modification of the HP-β-CyD molecule did not influence the encapsulation of ibuprofen, as a similar encapsulation efficiency was obtained for an inclusion complex prepared with mono-1-glucose-β-CyD. Copyright © 2015 Elsevier B.V. All rights reserved.

Free radical scavenging activity and neuroprotective potentials of D138, one Cu(II)/Zn(II) Schiff-base complex derived from N,N'-bis(2-hydroxynaphthylmethylidene)-1,3-propanediamine.

PubMed

Wang, Che; Cai, Zheng-Xu; You, Zhong-Lu; Guo, Hui-Shu; Shang, De-Jing; Wang, Xiao-Ling; Zhang, Liang; Ma, Li-Jie; Tan, Jun; Le, Wei-Dong; Li, Song

2014-09-01

There is increasing evidence that free radicals play an important role in neuronal damages induced by diabetes mellitus or cerebral ischemia insults. Antioxidants with free radical scavenging activities have been shown to be beneficial and neuroprotective for these pathological conditions. Here, we report free radical scavenging activity and neuroprotective potential of D138, one copper(II)/zinc(II) Schiff-base complex derived from N,N'-2(2-hydroxynaphthylmethylidene)-1,3-propanediamine. The data from three in vitro assays, 2,2-diphenyl-1-picrylhydrazyl assay, nitro blue tetrazolium assay and hydroxyl radical scavenging assay, indicated that D138 presented a potent free radical scavenging activity. The neuroprotective and antioxidative effects of D138 were further evaluated in vivo using bilateral common carotid artery occlusion (BCCAO) mouse model and streptozotocin (STZ) diabetic mouse model. Our results indicated that treatment of D138 significantly ameliorated the hippocampal neuronal damage and the oxidative stress levels in these animal models. Moreover, D138 also reversed the behavioral deficiencies induced by BCCAO or STZ, as assessed by Y-maze test and fear conditioning test. In conclusion, all these findings support that D138 exerts free radical scavenging and neuroprotective activities and has the potentials to be a potent therapeutic candidate for brain oxidative damage induced by cerebral ischemia or diabetes mellitus.

Interdependency of formation and localisation of the Min complex controls symmetric plastid division.

PubMed

Maple, Jodi; Møller, Simon G

2007-10-01

Plastid division represents a fundamental biological process essential for plant development; however, the molecular basis of symmetric plastid division is unclear. AtMinE1 plays a pivotal role in selection of the plastid division site in concert with AtMinD1. AtMinE1 localises to discrete foci in chloroplasts and interacts with AtMinD1, which shows a similar localisation pattern. Here, we investigate the importance of Min protein complex formation during the chloroplast division process. Dissection of the assembly of the Min protein complex and determination of the interdependency of complex assembly and localisation in planta allow us to present a model of the molecular basis of selection of the division site in plastids. Moreover, functional analysis of AtMinE1 in bacteria demonstrates the level of functional conservation and divergence of the plastidic MinE proteins.

Utilisation of three-dimensional printed heart models for operative planning of complex congenital heart defects.

PubMed

Olejník, Peter; Nosal, Matej; Havran, Tomas; Furdova, Adriana; Cizmar, Maros; Slabej, Michal; Thurzo, Andrej; Vitovic, Pavol; Klvac, Martin; Acel, Tibor; Masura, Jozef

2017-01-01

To evaluate the accuracy of the three-dimensional (3D) printing of cardiovascular structures. To explore whether utilisation of 3D printed heart replicas can improve surgical and catheter interventional planning in patients with complex congenital heart defects. Between December 2014 and November 2015 we fabricated eight cardiovascular models based on computed tomography data in patients with complex spatial anatomical relationships of cardiovascular structures. A Bland-Altman analysis was used to assess the accuracy of 3D printing by comparing dimension measurements at analogous anatomical locations between the printed models and digital imagery data, as well as between printed models and in vivo surgical findings. The contribution of 3D printed heart models for perioperative planning improvement was evaluated in the four most representative patients. Bland-Altman analysis confirmed the high accuracy of 3D cardiovascular printing. Each printed model offered an improved spatial anatomical orientation of cardiovascular structures. Current 3D printers can produce authentic copies of patients` cardiovascular systems from computed tomography data. The use of 3D printed models can facilitate surgical or catheter interventional procedures in patients with complex congenital heart defects due to better preoperative planning and intraoperative orientation.

Sensitivity Analysis and Parameter Estimation for a Reactive Transport Model of Uranium Bioremediation

NASA Astrophysics Data System (ADS)

Meyer, P. D.; Yabusaki, S.; Curtis, G. P.; Ye, M.; Fang, Y.

2011-12-01

A three-dimensional, variably-saturated flow and multicomponent biogeochemical reactive transport model of uranium bioremediation was used to generate synthetic data . The 3-D model was based on a field experiment at the U.S. Dept. of Energy Rifle Integrated Field Research Challenge site that used acetate biostimulation of indigenous metal reducing bacteria to catalyze the conversion of aqueous uranium in the +6 oxidation state to immobile solid-associated uranium in the +4 oxidation state. A key assumption in past modeling studies at this site was that a comprehensive reaction network could be developed largely through one-dimensional modeling. Sensitivity analyses and parameter estimation were completed for a 1-D reactive transport model abstracted from the 3-D model to test this assumption, to identify parameters with the greatest potential to contribute to model predictive uncertainty, and to evaluate model structure and data limitations. Results showed that sensitivities of key biogeochemical concentrations varied in space and time, that model nonlinearities and/or parameter interactions have a significant impact on calculated sensitivities, and that the complexity of the model's representation of processes affecting Fe(II) in the system may make it difficult to correctly attribute observed Fe(II) behavior to modeled processes. Non-uniformity of the 3-D simulated groundwater flux and averaging of the 3-D synthetic data for use as calibration targets in the 1-D modeling resulted in systematic errors in the 1-D model parameter estimates and outputs. This occurred despite using the same reaction network for 1-D modeling as used in the data-generating 3-D model. Predictive uncertainty of the 1-D model appeared to be significantly underestimated by linear parameter uncertainty estimates.

Developmental Hypothyroxinemia and Hypothyroidism Reduce Parallel Fiber-Purkinje Cell Synapses in Rat Offspring by Downregulation of Neurexin1/Cbln1/GluD2 Tripartite Complex.

PubMed

Wang, Yuan; Dong, Jing; Wang, Yi; Wei, Wei; Song, Binbin; Shan, Zhongyan; Teng, Weiping; Chen, Jie

2016-10-01

Iodine is a significant micronutrient. Iodine deficiency (ID)-induced hypothyroxinemia and hypothyroidism during developmental period can cause cerebellar dysfunction. However, mechanisms are still unclear. Therefore, the present research aims to study effects of developmental hypothyroxinemia caused by mild ID and hypothyroidism caused by severe ID or methimazole (MMZ) on parallel fiber-Purkinje cell (PF-PC) synapses in filial cerebellum. Maternal hypothyroxinemia and hypothyroidism models were established in Wistar rats using ID diet and deionized water supplemented with different concentrations of potassium iodide or MMZ water. Birth weight and cerebellum weight were measured. We also examined PF-PC synapses using immunofluorescence, and western blot analysis was conducted to investigate the activity of Neurexin1/cerebellin1 (Cbln1)/glutamate receptor d2 (GluD2) tripartite complex. Our results showed that hypothyroxinemia and hypothyroidism decreased birth weight and cerebellum weight and reduced the PF-PC synapses on postnatal day (PN) 14 and PN21. Accordingly, the mean intensity of vesicular glutamate transporter (VGluT1) and Calbindin immunofluorescence was reduced in mild ID, severe ID, and MMZ groups. Moreover, maternal hypothyroxinemia and hypothyroidism reduced expression of Neurexin1/Cbln1/GluD2 tripartite complex. Our study supports the hypothesis that developmental hypothyroxinemia and hypothyroidism reduce PF-PC synapses, which may be attributed to the downregulation of Neurexin1/Cbln1/GluD2 tripartite complex.

The use of high field/frequency EPR in studies of radical and metal sites in proteins and small inorganic models

NASA Astrophysics Data System (ADS)

Andersson, K. Kristoffer; Barra, Anne-Laure

2002-04-01

Low temperature electron paramagnetic resonance (EPR) spectroscopy with frequencies between 95 and 345 GHz and magnetic fields up to 12 T have been used to study radicals and metal sites in proteins and small inorganic model complexes. We have studied radicals, Fe, Cu and Mn containing proteins. For S=1/2 systems, the high frequency method can resolve the g-value anisotropy. It was used in mouse ribonucleotide reductase (RNR) to show the presence of a hydrogen bond to the tyrosyl radical oxygen. At 285 GHz the type 2 Cu(II) signal in the complex enzyme laccase is clearly resolved from the Hg(II) containing laccase peroxide adduct. For simple metal sites, the systems over S=1/2 can be described by the spin Hamiltonian: HS= BgS+ D[ Sz2- S( S+1)/3+ E/ D ( Sx2- Sy2)]. From the high frequency EPR the D-value can be determined directly by, (I) shifts of geff for half-integer spin systems with large D-values as observed at 345 GHz on an Fe(II)NOEDTA complex, which is best described as S=3/2 system with D=11.5 cm -1, E=0.1 cm -1 and gx= gy= gz=2.0; (II) measuring the outermost signal, for systems with small D values, distant of (2 S-1)*∣ D∣ from the center of the spectrum as observed in S=5/2 Fe(III)EDTA. In Mn(II) substituted mouse RNR R2 protein the weakly interacting Mn(II) at X-band could be observed as decoupled Mn(II) at 285 GHz.

Advanced Waveform Simulation for Seismic Monitoring

DTIC Science & Technology

2008-09-01

velocity model. The method separates the main arrivals of the regional waveform into 5 windows: Pnl (vertical and radial components), Rayleigh (vertical and...ranges out to 10°, including extensive observations of crustal thinning and thickening and various Pnl complexities. Broadband modeling in 1D, 2D...existing models perform in predicting the various regional phases, Rayleigh waves, Love waves, and Pnl waves. Previous events from this Basin-and-Range

Complex Physical, Biophysical and Econophysical Systems

NASA Astrophysics Data System (ADS)

Dewar, Robert L.; Detering, Frank

1. Introduction to complex and econophysics systems: a navigation map / T. Aste and T. Di Matteo -- 2. An introduction to fractional diffusion / B. I. Henry, T.A.M. Langlands and P. Straka -- 3. Space plasmas and fusion plasmas as complex systems / R. O. Dendy -- 4. Bayesian data analysis / M. S. Wheatland -- 5. Inverse problems and complexity in earth system science / I. G. Enting -- 6. Applied fluid chaos: designing advection with periodically reoriented flows for micro to geophysical mixing and transport enhancement / G. Metcalfe -- 7. Approaches to modelling the dynamical activity of brain function based on the electroencephalogram / D. T. J. Liley and F. Frascoli -- 8. Jaynes' maximum entropy principle, Riemannian metrics and generalised least action bound / R. K. Niven and B. Andresen -- 9. Complexity, post-genomic biology and gene expression programs / R. B. H. Williams and O. J.-H. Luo -- 10. Tutorials on agent-based modelling with NetLogo and network analysis with Pajek / M. J. Berryman and S. D. Angus.

The assembly, activation, and substrate specificity of Cyclin D1/Cdk2 complexes

PubMed Central

Jahn, Stephan C.; Law, Mary E.; Corsino, Patrick E.; Rowe, Thomas C.; Davis, Bradley J.; Law, Brian K.

2013-01-01

Previous studies have shown conflicting data regarding Cyclin D1/Cdk2 complexes and, considering the widespread overexpression of Cyclin D1 in cancer, it is important to fully understand their relevance. While many have shown Cyclin D1/Cdk2 complexes to form active complexes, others have failed to show activity or association. Here, using a novel p21-PCNA fusion protein as well as p21 mutant proteins, we show that p21 is a required scaffolding protein, with Cyclin D1 and Cdk2 failing to complex in its absence. These p21/Cyclin D1/Cdk2 complexes are active and also bind the trimeric PCNA complex, with each trimer capable of independently binding distinct Cyclin/Cdk complexes. We also show that increased p21 levels due to treatment with chemotherapeutic agents result in increased formation and kinase activity of Cyclin D1/Cdk2 complexes, and that Cyclin D1/Cdk2 complexes are able to phosphorylate a number of substrates in addition to Rb. Nucleophosmin and Cdh1, two proteins important for centrosome replication and implicated in the chromosomal instability of cancer are shown to be phosphorylated by Cyclin D1/Cdk2 complexes. Additionally, PSF is identified as a novel Cdk2 substrate, being phosphorylated by Cdk2 complexed with either Cyclin E or Cyclin D1, and given the many functions of PSF, it could have important implications on cellular activity. PMID:23627734

Evaluation of 2D shallow-water model for spillway flow with a complex geometry

USDA-ARS?s Scientific Manuscript database

Although the two-dimensional (2D) shallow water model is formulated based on several assumptions such as hydrostatic pressure distribution and vertical velocity is negligible, as a simple alternative to the complex 3D model, it has been used to compute water flows in which these assumptions may be ...

Flood hazard assessment using 1D and 2D approaches

NASA Astrophysics Data System (ADS)

Petaccia, Gabriella; Costabile, Pierfranco; Macchione, Francesco; Natale, Luigi

2013-04-01

The EU flood risk Directive (Directive 2007/60/EC) prescribes risk assessment and mapping to develop flood risk management plans. Flood hazard mapping may be carried out with mathematical models able to determine flood-prone areas once realistic conditions (in terms of discharge or water levels) are imposed at the boundaries of the case study. The deterministic models are mainly based on shallow water equations expressed in their 1D or 2D formulation. The 1D approach is widely used, especially in technical studies, due to its relative simplicity, its computational efficiency and also because it requires topographical data not as expensive as the ones needed by 2D models. Even if in a great number of practical situations, such as modeling in-channel flows and not too wide floodplains, the 1D approach may provide results close to the prediction of a more sophisticated 2D model, it must be pointed out that the correct use of a 1D model in practical situations is more complex than it may seem. The main issues to be correctly modeled in a 1D approach are the definition of hydraulic structures such as bridges and buildings interacting with the flow and the treatment of the tributaries. Clearly all these aspects have to be taken into account also in the 2D modeling, but with fewer difficulties. The purpose of this paper is to show how the above cited issues can be described using a 1D or 2D unsteady flow modeling. In particular the Authors will show the devices that have to be implemented in 1D modeling to get reliable predictions of water levels and discharges comparable to the ones obtained using a 2D model. Attention will be focused on an actual river (Crati river) located in the South of Italy. This case study is quite complicated since it deals with the simulation of channeled flows, overbank flows, interactions with buildings, bridges and tributaries. Accurate techniques, intentionally developed by the Authors to take into account all these peculiarities in 1D and 2D modeling, will be presented, compared and discussed.

Simulations of Seismic Wave Propagation on Mars

DOE PAGES

Bozdağ, Ebru; Ruan, Youyi; Metthez, Nathan; ...

2017-03-23

In this paper, we present global and regional synthetic seismograms computed for 1D and 3D Mars models based on the spectral-element method. For global simulations, we implemented a radially-symmetric Mars model with a 110 km thick crust. For this 1D model, we successfully benchmarked the 3D seismic wave propagation solver SPECFEM3D_GLOBE against the 2D axisymmetric wave propagation solver AxiSEM at periods down to 10 s. We also present higher-resolution body-wave simulations with AxiSEM down to 1 s in a model with a more complex 1D crust, revealing wave propagation effects that would have been difficult to interpret based on raymore » theory. For 3D global simulations based on SPECFEM3D_GLOBE, we superimposed 3D crustal thickness variations capturing the distinct crustal dichotomy between Mars’ northern and southern hemispheres, as well as topography, ellipticity, gravity, and rotation. The global simulations clearly indicate that the 3D crust speeds up body waves compared to the reference 1D model, whereas it significantly changes surface waveforms and their dispersive character depending on its thickness. We also perform regional simulations with the solver SES3D based on 3D crustal models derived from surface composition, thereby addressing the effects of various distinct crustal features down to 2 s. The regional simulations confirm the strong effects of crustal variations on waveforms. Finally, we conclude that the numerical tools are ready for examining more scenarios, including various other seismic models and sources.« less

Simulations of Seismic Wave Propagation on Mars

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

Bozdağ, Ebru; Ruan, Youyi; Metthez, Nathan

In this paper, we present global and regional synthetic seismograms computed for 1D and 3D Mars models based on the spectral-element method. For global simulations, we implemented a radially-symmetric Mars model with a 110 km thick crust. For this 1D model, we successfully benchmarked the 3D seismic wave propagation solver SPECFEM3D_GLOBE against the 2D axisymmetric wave propagation solver AxiSEM at periods down to 10 s. We also present higher-resolution body-wave simulations with AxiSEM down to 1 s in a model with a more complex 1D crust, revealing wave propagation effects that would have been difficult to interpret based on raymore » theory. For 3D global simulations based on SPECFEM3D_GLOBE, we superimposed 3D crustal thickness variations capturing the distinct crustal dichotomy between Mars’ northern and southern hemispheres, as well as topography, ellipticity, gravity, and rotation. The global simulations clearly indicate that the 3D crust speeds up body waves compared to the reference 1D model, whereas it significantly changes surface waveforms and their dispersive character depending on its thickness. We also perform regional simulations with the solver SES3D based on 3D crustal models derived from surface composition, thereby addressing the effects of various distinct crustal features down to 2 s. The regional simulations confirm the strong effects of crustal variations on waveforms. Finally, we conclude that the numerical tools are ready for examining more scenarios, including various other seismic models and sources.« less

Network geometry with flavor: From complexity to quantum geometry

NASA Astrophysics Data System (ADS)

Bianconi, Ginestra; Rahmede, Christoph

2016-03-01

Network geometry is attracting increasing attention because it has a wide range of applications, ranging from data mining to routing protocols in the Internet. At the same time advances in the understanding of the geometrical properties of networks are essential for further progress in quantum gravity. In network geometry, simplicial complexes describing the interaction between two or more nodes play a special role. In fact these structures can be used to discretize a geometrical d -dimensional space, and for this reason they have already been widely used in quantum gravity. Here we introduce the network geometry with flavor s =-1 ,0 ,1 (NGF) describing simplicial complexes defined in arbitrary dimension d and evolving by a nonequilibrium dynamics. The NGF can generate discrete geometries of different natures, ranging from chains and higher-dimensional manifolds to scale-free networks with small-world properties, scale-free degree distribution, and nontrivial community structure. The NGF admits as limiting cases both the Bianconi-Barabási models for complex networks, the stochastic Apollonian network, and the recently introduced model for complex quantum network manifolds. The thermodynamic properties of NGF reveal that NGF obeys a generalized area law opening a new scenario for formulating its coarse-grained limit. The structure of NGF is strongly dependent on the dimensionality d . In d =1 NGFs grow complex networks for which the preferential attachment mechanism is necessary in order to obtain a scale-free degree distribution. Instead, for NGF with dimension d >1 it is not necessary to have an explicit preferential attachment rule to generate scale-free topologies. We also show that NGF admits a quantum mechanical description in terms of associated quantum network states. Quantum network states evolve by a Markovian dynamics and a quantum network state at time t encodes all possible NGF evolutions up to time t . Interestingly the NGF remains fully classical but its statistical properties reveal the relation to its quantum mechanical description. In fact the δ -dimensional faces of the NGF have generalized degrees that follow either the Fermi-Dirac, Boltzmann, or Bose-Einstein statistics depending on the flavor s and the dimensions d and δ .

Network geometry with flavor: From complexity to quantum geometry.

PubMed

Bianconi, Ginestra; Rahmede, Christoph

2016-03-01

Network geometry is attracting increasing attention because it has a wide range of applications, ranging from data mining to routing protocols in the Internet. At the same time advances in the understanding of the geometrical properties of networks are essential for further progress in quantum gravity. In network geometry, simplicial complexes describing the interaction between two or more nodes play a special role. In fact these structures can be used to discretize a geometrical d-dimensional space, and for this reason they have already been widely used in quantum gravity. Here we introduce the network geometry with flavor s=-1,0,1 (NGF) describing simplicial complexes defined in arbitrary dimension d and evolving by a nonequilibrium dynamics. The NGF can generate discrete geometries of different natures, ranging from chains and higher-dimensional manifolds to scale-free networks with small-world properties, scale-free degree distribution, and nontrivial community structure. The NGF admits as limiting cases both the Bianconi-Barabási models for complex networks, the stochastic Apollonian network, and the recently introduced model for complex quantum network manifolds. The thermodynamic properties of NGF reveal that NGF obeys a generalized area law opening a new scenario for formulating its coarse-grained limit. The structure of NGF is strongly dependent on the dimensionality d. In d=1 NGFs grow complex networks for which the preferential attachment mechanism is necessary in order to obtain a scale-free degree distribution. Instead, for NGF with dimension d>1 it is not necessary to have an explicit preferential attachment rule to generate scale-free topologies. We also show that NGF admits a quantum mechanical description in terms of associated quantum network states. Quantum network states evolve by a Markovian dynamics and a quantum network state at time t encodes all possible NGF evolutions up to time t. Interestingly the NGF remains fully classical but its statistical properties reveal the relation to its quantum mechanical description. In fact the δ-dimensional faces of the NGF have generalized degrees that follow either the Fermi-Dirac, Boltzmann, or Bose-Einstein statistics depending on the flavor s and the dimensions d and δ.

Membrane interaction of antimicrobial peptides using E. coli lipid extract as model bacterial cell membranes and SFG spectroscopy.

PubMed

Soblosky, Lauren; Ramamoorthy, Ayyalusamy; Chen, Zhan

2015-04-01

Supported lipid bilayers are used as a convenient model cell membrane system to study biologically important molecule-lipid interactions in situ. However, the lipid bilayer models are often simple and the acquired results with these models may not provide all pertinent information related to a real cell membrane. In this work, we use sum frequency generation (SFG) vibrational spectroscopy to study molecular-level interactions between the antimicrobial peptides (AMPs) MSI-594, ovispirin-1 G18, magainin 2 and a simple 1,2-dipalmitoyl-d62-sn-glycero-3-phosphoglycerol (dDPPG)/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) bilayer. We compared such interactions to those between the AMPs and a more complex dDPPG/Escherichia coli (E. coli) polar lipid extract bilayer. We show that to fully understand more complex aspects of peptide-bilayer interaction, such as interaction kinetics, a heterogeneous lipid composition is required, such as the E. coli polar lipid extract. The discrepancy in peptide-bilayer interaction is likely due in part to the difference in bilayer charge between the two systems since highly negative charged lipids can promote more favorable electrostatic interactions between the peptide and lipid bilayer. Results presented in this paper indicate that more complex model bilayers are needed to accurately analyze peptide-cell membrane interactions and demonstrates the importance of using an appropriate lipid composition to study AMP interaction properties. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Characterizing and modeling organic binder burnout from green ceramic compacts

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

Ewsuk, K.G.; Cesarano, J. III; Cochran, R.J.

New characterization and computational techniques have been developed to evaluate and simulate binder burnout from pressed powder compacts. Using engineering data and a control volume finite element method (CVFEM) thermal model, a nominally one dimensional (1-D) furnace has been designed to test, refine, and validate computer models that simulate binder burnout assuming a 1-D thermal gradient across the ceramic body during heating. Experimentally, 1-D radial heat flow was achieved using a rod-shaped heater that directly heats the inside surface of a stack of ceramic annuli surrounded by thermal insulation. The computational modeling effort focused on producing a macroscopic model formore » binder burnout based on continuum approaches to heat and mass conservation for porous media. Two increasingly complex models have been developed that predict the temperature and mass of a porous powder compact as a function of time during binder burnout. The more complex model also predicts the pressure within a powder compact during binder burnout. Model predictions are in reasonably good agreement with experimental data on binder burnout from a 57--65% relative density pressed powder compact of a 94 wt% alumina body containing {approximately}3 wt% binder. In conjunction with the detailed experimental data from the prototype binder burnout furnace, the models have also proven useful for conducting parametric studies to elucidate critical i-material property data required to support model development.« less

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

Watts, David; Wang, Daoyong; Adelberg, Mackenzie

A novel sulfonated CNN pincer ligand has been designed to support CH and O 2 activation at a Pt(II) center. The derived cycloplatinated aqua complex 7 was found to be one of the most active reported homogeneous Pt catalysts for H/D exchange between studied arenes (benzene, benzene-d 6, toluene-d 8, p-xylene, and mesitylene) and 2,2,2-trifluoroethanol (TFE) or 2,2,2-trifluoroethanol-d; the TON for C 6D 6 as a substrate is >250 after 48 h at 80 °C. The reaction is very selective; no benzylic CH bond activation was observed. The per-CH-bond reactivity diminishes in the series benzene (19) > toluene ( p-CH:more » m-CH: o-CH = 1:0.9:0.2) > xylene (2.9) > mesitylene (1.1). The complex 7 reacts slowly in TFE solutions under ambient light but not in the dark with O 2 to selectively produce a Pt(IV) trifluoroethoxo derivative. The H/D exchange reaction kinetics and results of the DFT study suggest that complex 7, and not its TFE derivatives, is the major species responsible for the arene CH bond activation. Lastly, the reaction deuterium kinetic isotope effect, k H/k D = 1.7, the reaction selectivity, and reaction kinetics modeling suggest that the CH bond cleavage step is rate-determining.« less

Towards a Framework for Modeling Space Systems Architectures

NASA Technical Reports Server (NTRS)

Shames, Peter; Skipper, Joseph

2006-01-01

Topics covered include: 1) Statement of the problem: a) Space system architecture is complex; b) Existing terrestrial approaches must be adapted for space; c) Need a common architecture methodology and information model; d) Need appropriate set of viewpoints. 2) Requirements on a space systems model. 3) Model Based Engineering and Design (MBED) project: a) Evaluated different methods; b) Adapted and utilized RASDS & RM-ODP; c) Identified useful set of viewpoints; d) Did actual model exchanges among selected subset of tools. 4) Lessons learned & future vision.

Predictive Engineering Tools for Injection-Molded Long-Carbon-Fiber Thermoplastic Composites - Fourth FY 2015 Quarterly Report

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

Nguyen, Ba Nghiep; Fifield, Leonard S.; Wollan, Eric J.

2015-11-13

During the last quarter of FY 2015, the following technical progress has been made toward project milestones: 1) PlastiComp used the PlastiComp direct in-line (D-LFT) Pushtrusion system to injection mold 40 30wt% LCF/PP parts with ribs, 40 30wt% LCF/PP parts without ribs, 10 30wt% LCF/PA66 parts with ribs, and 35 30wt% LCF/PA66 parts without ribs. In addition, purge materials from the injection molding nozzle were obtained for fiber length analysis, and molding parameters were sent to PNNL for process modeling. 2) Magna cut samples at four selected locations (named A, B, C and D) from the non-ribbed Magna-molded parts basedmore » on a plan discussed with PNNL and the team and shipped these samples to Virginia Tech for fiber orientation and length measurements. 3) Virginia Tech started fiber orientation and length measurements for the samples taken from the complex parts using Virginia Tech’s established procedure. 4) PNNL and Autodesk built ASMI models for the complex parts with and without ribs, reviewed process datasheets and performed preliminary analyses of these complex parts using the actual molding parameters received from Magna and PlastiComp to compare predicted to experimental mold filling patterns. 5) Autodesk assisted PNNL in developing the workflow to use Moldflow fiber orientation and length results in ABAQUS® simulations. 6) Autodesk advised the team on the practicality and difficulty of material viscosity characterization from the D-LFT process. 7) PNNL developed a procedure to import fiber orientation and length results from a 3D ASMI analysis to a 3D ABAQUS® model for structural analyses of the complex part for later weight reduction study. 8) In discussion with PNNL and Magna, Toyota developed mechanical test setups and built fixtures for three-point bending and torsion tests of the complex parts. 9) Toyota built a finite element model for the complex parts subjected to torsion loading. 10) PNNL built the 3D ABAQUS® model of the complex ribbed part subjected to 3-point bending. 11) University of Illinois (Prof. C.L. Tucker) advised the team on fiber orientation and fiber length measurement options, modeling issues as well as interpretation of data.« less

Electron microscopy and in vitro deneddylation reveal similar architectures and biochemistry of isolated human and Flag-mouse COP9 signalosome complexes

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

Rockel, Beate; Schmaler, Tilo; Huang, Xiaohua

2014-07-25

Highlights: • Deneddylation rates of human erythrocyte and mouse fibroblast CSN are very similar. • 3D models of native human and mouse CSN reveal common architectures. • The cryo-structure of native mammalian CSN shows a horseshoe subunit arrangement. - Abstract: The COP9 signalosome (CSN) is a regulator of the ubiquitin (Ub) proteasome system (UPS). In the UPS, proteins are Ub-labeled for degradation by Ub ligases conferring substrate specificity. The CSN controls a large family of Ub ligases called cullin-RING ligases (CRLs), which ubiquitinate cell cycle regulators, transcription factors and DNA damage response proteins. The CSN possesses structural similarities with themore » 26S proteasome Lid complex and the translation initiation complex 3 (eIF3) indicating similar ancestry and function. Initial structures were obtained 14 years ago by 2D electron microscopy (EM). Recently, first 3D molecular models of the CSN were created on the basis of negative-stain EM and single-particle analysis, mostly with recombinant complexes. Here, we compare deneddylating activity and structural features of CSN complexes purified in an elaborate procedure from human erythrocytes and efficiently pulled down from mouse Flag-CSN2 B8 fibroblasts. In an in vitro deneddylation assay both the human and the mouse CSN complexes deneddylated Nedd8-Cul1 with comparable rates. 3D structural models of the erythrocyte CSN as well as of the mouse Flag-CSN were generated by negative stain EM and by cryo-EM. Both complexes show a central U-shaped segment from which several arms emanate. This structure, called the horseshoe, is formed by the PCI domain subunits. CSN5 and CSN6 point away from the horseshoe. Compared to 3D models of negatively stained CSN complexes, densities assigned to CSN2 and CSN4 are better defined in the cryo-map. Because biochemical and structural results obtained with CSN complexes isolated from human erythrocytes and purified by Flag-CSN pulldown from mouse B8 fibroblasts are very similar, Flag-CSN pulldowns are a proper alternative to CSN preparation from erythrocytes.« less

Effects of 3 dimensional crystal geometry and orientation on 1D and 2D time-scale determinations of magmatic processes using olivine and orthopyroxene

NASA Astrophysics Data System (ADS)

Shea, Thomas; Krimer, Daniel; Costa, Fidel; Hammer, Julia

2014-05-01

One of the achievements in recent years in volcanology is the determination of time-scales of magmatic processes via diffusion in minerals and its addition to the petrologists' and volcanologists' toolbox. The method typically requires one-dimensional modeling of randomly cut crystals from two-dimensional thin sections. Here we address the question whether using 1D (traverse) or 2D (surface) datasets exploited from randomly cut 3D crystals introduces a bias or dispersion in the time-scales estimated, and how this error can be improved or eliminated. Computational simulations were performed using a concentration-dependent, finite-difference solution to the diffusion equation in 3D. The starting numerical models involved simple geometries (spheres, parallelepipeds), Mg/Fe zoning patterns (either normal or reverse), and isotropic diffusion coefficients. Subsequent models progressively incorporated more complexity, 3D olivines possessing representative polyhedral morphologies, diffusion anisotropy along the different crystallographic axes, and more intricate core-rim zoning patterns. Sections and profiles used to compare 1, 2 and 3D diffusion models were selected to be (1) parallel to the crystal axes, (2) randomly oriented but passing through the olivine center, or (3) randomly oriented and sectioned. Results show that time-scales estimated on randomly cut traverses (1D) or surfaces (2D) can be widely distributed around the actual durations of 3D diffusion (~0.2 to 10 times the true diffusion time). The magnitude over- or underestimations of duration are a complex combination of the geometry of the crystal, the zoning pattern, the orientation of the cuts with respect to the crystallographic axes, and the degree of diffusion anisotropy. Errors on estimated time-scales retrieved from such models may thus be significant. Drastic reductions in the uncertainty of calculated diffusion times can be obtained by following some simple guidelines during the course of data collection (i.e. selection of crystals and concentration profiles, acquisition of crystallographic orientation data), thus allowing derivation of robust time-scales.

Scattering of particles in the presence of harmonic confinement perturbed by a complex absorbing potential

NASA Astrophysics Data System (ADS)

Maghari, A.; Kermani, M. M.

2018-04-01

A system of two interacting atoms confined in 1D harmonic trap and perturbed by an absorbing boundary potential is studied using the Lippmann-Schwinger formalism. The atom-atom interaction potential was considered as a nonlocal separable model. The perturbed absorbing boundary potential was also assumed in the form of Scarf II complex absorbing potential. The model is used for the study of 1D optical lattices that support the trapping of a pair atom within a unit cell. Moreover, it allows to describe the scattering particles in a tight smooth trapping surface and to analyze the bound and resonance states. The analytical expressions for wavefunctions and transition matrix as well as the absorption probabilities are calculated. A demonstration of how the complex absorbing potential affecting the bound states and resonances of particles confined in a harmonic trap is described.

Protocols and characterization data for 2D, 3D, and slice-based tumor models from the PREDECT project.

PubMed

de Hoogt, Ronald; Estrada, Marta F; Vidic, Suzana; Davies, Emma J; Osswald, Annika; Barbier, Michael; Santo, Vítor E; Gjerde, Kjersti; van Zoggel, Hanneke J A A; Blom, Sami; Dong, Meng; Närhi, Katja; Boghaert, Erwin; Brito, Catarina; Chong, Yolanda; Sommergruber, Wolfgang; van der Kuip, Heiko; van Weerden, Wytske M; Verschuren, Emmy W; Hickman, John; Graeser, Ralph

2017-11-21

Two-dimensional (2D) culture of cancer cells in vitro does not recapitulate the three-dimensional (3D) architecture, heterogeneity and complexity of human tumors. More representative models are required that better reflect key aspects of tumor biology. These are essential studies of cancer biology and immunology as well as for target validation and drug discovery. The Innovative Medicines Initiative (IMI) consortium PREDECT (www.predect.eu) characterized in vitro models of three solid tumor types with the goal to capture elements of tumor complexity and heterogeneity. 2D culture and 3D mono- and stromal co-cultures of increasing complexity, and precision-cut tumor slice models were established. Robust protocols for the generation of these platforms are described. Tissue microarrays were prepared from all the models, permitting immunohistochemical analysis of individual cells, capturing heterogeneity. 3D cultures were also characterized using image analysis. Detailed step-by-step protocols, exemplary datasets from the 2D, 3D, and slice models, and refined analytical methods were established and are presented.

Protocols and characterization data for 2D, 3D, and slice-based tumor models from the PREDECT project

PubMed Central

de Hoogt, Ronald; Estrada, Marta F.; Vidic, Suzana; Davies, Emma J.; Osswald, Annika; Barbier, Michael; Santo, Vítor E.; Gjerde, Kjersti; van Zoggel, Hanneke J. A. A.; Blom, Sami; Dong, Meng; Närhi, Katja; Boghaert, Erwin; Brito, Catarina; Chong, Yolanda; Sommergruber, Wolfgang; van der Kuip, Heiko; van Weerden, Wytske M.; Verschuren, Emmy W.; Hickman, John; Graeser, Ralph

2017-01-01

Two-dimensional (2D) culture of cancer cells in vitro does not recapitulate the three-dimensional (3D) architecture, heterogeneity and complexity of human tumors. More representative models are required that better reflect key aspects of tumor biology. These are essential studies of cancer biology and immunology as well as for target validation and drug discovery. The Innovative Medicines Initiative (IMI) consortium PREDECT (www.predect.eu) characterized in vitro models of three solid tumor types with the goal to capture elements of tumor complexity and heterogeneity. 2D culture and 3D mono- and stromal co-cultures of increasing complexity, and precision-cut tumor slice models were established. Robust protocols for the generation of these platforms are described. Tissue microarrays were prepared from all the models, permitting immunohistochemical analysis of individual cells, capturing heterogeneity. 3D cultures were also characterized using image analysis. Detailed step-by-step protocols, exemplary datasets from the 2D, 3D, and slice models, and refined analytical methods were established and are presented. PMID:29160867

Waveform complexity caused by near trench structure and its impact on earthquake source study: application to the 2015 Illapel earthquake sequence

NASA Astrophysics Data System (ADS)

Qian, Y.; Wei, S.; Wu, W.; Ni, S.

2017-12-01

Among various types of 3D heterogeneity in the Earth, trench might be the most complex systems, which includes rapidly varying bathymetry and usually thick sediment below water layer. These structure complexities can cause substantial waveform complexities on seismograms, but their corresponding impact on the earthquake source studies has not yet been well understood. Here we explore those effects via studies of two moderate aftershocks (one near the coast while the other close to the Peru-Chile trench axis) in the 2015 Illapel earthquake sequence. The horizontal locations and depths of these two events are poorly constrained and the reported results of various agencies display substantial variations. Thus, we first relocated the epicenters using the P-wave first arrivals and determined other parameters by waveform fitting. In a jackknifing way, we found that the trench event has large differences between regional and teleseismic solutions, in particular for depth, while the coastal event shows consistent results. The teleseismic P/Pdiff waves between these two events also display distinctly different features. More specifically, the trench event has more complex P/Pdiff waves and stronger coda waves, in terms of amplitude and duration (longer than 100s). The coda waves are coherent across stations at different distances and azimuths, indicating a more likely origin of scattering waves due to 3D heterogeneity near trench. To quantitatively model those 3D effects, we adopted a hybrid waveform simulation approach that computes the 3D wavefield in the source region by the Spectral Element Method (SEM) and then propagates the wavefield to teleseismic and shadow zone distances through the Direct Solution Method (DSM). We incorporated the GEBCO bathymetry and water layer into the SEM simulations and assumed the IASP91 1D model for DSM computation. Comparing with the poor 1D synthetics fitting to the data, we do obtain dramatic improvement in 3D waveform fittings across a series of frequency bands. With sensitivity tests of 3D waveform modeling, the centroid longitude and depth for the near trench event are refined. Our study suggests that the complex trench structure must be taken into account for a reliable analysis of shallow earthquake near trench, in particular for the shallowest tsunamigenic earthquakes.

The application of 3-dimensional printing for preoperative planning in oral and maxillofacial surgery in dogs and cats.

PubMed

Winer, Jenna N; Verstraete, Frank J M; Cissell, Derek D; Lucero, Steven; Athanasiou, Kyriacos A; Arzi, Boaz

2017-10-01

To describe the application of 3-dimensional (3D) printing in advanced oral and maxillofacial surgery (OMFS) and to discuss the benefits of this modality in surgical planning, student and resident training, and client education. Retrospective case series. Client-owned dogs (n = 28) and cats (n = 4) with 3D printing models of the skulls. The medical records of 32 cases with 3D printing prior to major OMFS were reviewed. Indications for 3D printing included preoperative planning for mandibular reconstruction after mandibulectomy (n = 12 dogs) or defect nonunion fracture (n = 6 dogs, 2 cats), mapping of ostectomy location for temporomandibular joint ankylosis or pseudoankylosis (n = 4 dogs), assessment of palatal defects (n = 2 dogs, 1 cat), improved understanding of complex anatomy in cases of neoplasia located in challenging locations (n = 2 dogs, 1 cat), and in cases of altered anatomy secondary to trauma (n = 2 dogs). In the authors' experience, 3D printed models serve as excellent tools for OMFS planning and resident training. Furthermore, 3D printed models are a valuable resource to improve clients' understanding of the pet's disorder and the recommended treatment. Three-dimensional printed models should be considered viable tools for surgical planning, resident training, and client education in candidates for complex OMFS. © 2017 The American College of Veterinary Surgeons.

Homology modelling of Drosophila cytochrome P450 enzymes associated with insecticide resistance.

PubMed

Jones, Robert T; Bakker, Saskia E; Stone, Deborah; Shuttleworth, Sally N; Boundy, Sam; McCart, Caroline; Daborn, Phillip J; ffrench-Constant, Richard H; van den Elsen, Jean M H

2010-10-01

Overexpression of the cytochrome P450 gene Cyp6g1 confers resistance against DDT and a broad range of other insecticides in Drosophila melanogaster Meig. In the absence of crystal structures of CYP6G1 or complexes with its substrates, structural studies rely on homology modelling and ligand docking to understand P450-substrate interactions. Homology models are presented for CYP6G1, a P450 associated with resistance to DDT and neonicotinoids, and two other enzymes associated with insecticide resistance in D. melanogaster, CYP12D1 and CYP6A2. The models are based on a template of the X-ray structure of the phylogenetically related human CYP3A4, which is known for its broad substrate specificity. The model of CYP6G1 has a much smaller active site cavity than the template. The cavity is also 'V'-shaped and is lined with hydrophobic residues, showing high shape and chemical complementarity with the molecular characteristics of DDT. Comparison of the DDT-CYP6G1 complex and a non-resistant CYP6A2 homology model implies that tight-fit recognition of this insecticide is important in CYP6G1. The active site can accommodate differently shaped substrates ranging from imidacloprid to malathion but not the pyrethroids permethrin and cyfluthrin. The CYP6G1, CYP12D1 and CYP6A2 homology models can provide a structural insight into insecticide resistance in flies overexpressing P450 enzymes with broad substrate specificities.

Permeability from complex conductivity: an evaluation of polarization magnitude versus relaxation time based geophysical length scales

NASA Astrophysics Data System (ADS)

Slater, L. D.; Robinson, J.; Weller, A.; Keating, K.; Robinson, T.; Parker, B. L.

2017-12-01

Geophysical length scales determined from complex conductivity (CC) measurements can be used to estimate permeability k when the electrical formation factor F describing the ratio between tortuosity and porosity is known. Two geophysical length scales have been proposed: [1] the imaginary conductivity σ" normalized by the specific polarizability cp; [2] the time constant τ multiplied by a diffusion coefficient D+. The parameters cp and D+ account for the control of fluid chemistry and/or varying minerology on the geophysical length scale. We evaluated the predictive capability of two recently presented CC permeability models: [1] an empirical formulation based on σ"; [2] a mechanistic formulation based on τ;. The performance of the CC models was evaluated against measured permeability; this performance was also compared against that of well-established k estimation equations that use geometric length scales to represent the pore scale properties controlling fluid flow. Both CC models predict permeability within one order of magnitude for a database of 58 sandstone samples, with the exception of those samples characterized by high pore volume normalized surface area Spor and more complex mineralogy including significant dolomite. Variations in cp and D+ likely contribute to the poor performance of the models for these high Spor samples. The ultimate value of such geophysical models for permeability prediction lies in their application to field scale geophysical datasets. Two observations favor the implementation of the σ" based model over the τ based model for field-scale estimation: [1] the limited range of variation in cp relative to D+; [2] σ" is readily measured using field geophysical instrumentation (at a single frequency) whereas τ requires broadband spectral measurements that are extremely challenging and time consuming to accurately measure in the field. However, the need for a reliable estimate of F remains a major obstacle to the field-scale implementation of either of the CC permeability models for k estimation.

3D printing to simulate laparoscopic choledochal surgery.

PubMed

Burdall, Oliver C; Makin, Erica; Davenport, Mark; Ade-Ajayi, Niyi

2016-05-01

Laparoscopic simulation has transformed skills acquisition for many procedures. However, realistic nonbiological simulators for complex reconstructive surgery are rare. Life-like tactile feedback is particularly difficult to reproduce. Technological innovations may contribute novel solutions to these shortages. We describe a hybrid model, harnessing 3D technology to simulate laparoscopic choledochal surgery for the first time. Digital hepatic anatomy images and standard laparoscopic trainer dimensions were employed to create an entry level laparoscopic choledochal surgery model. The information was fed into a 3D systems project 660pro with visijet pxl core powder to create a free standing liver mold. This included a cuboid portal in which to slot disposable hybrid components representing hepatic and pancreatic ducts and choledochal cyst. The mold was used to create soft silicone replicas with T28 resin and T5 fast catalyst. The model was assessed at a national pediatric surgery training day. The 10 delegates that trialed the simulation felt that the tactile likeness was good (5.6/10±1.71, 10=like the real thing), was not too complex (6.2/10±1.35; where 1=too simple, 10=too complicated), and generally very useful (7.36/10±1.57, 10=invaluable). 100% stated that they felt they could reproduce this in their own centers, and 100% would recommend this simulation to colleagues. Though this first phase choledochal cyst excision simulation requires further development, 3D printing provides a useful means of creating specific and detailed simulations for rare and complex operations with huge potential for development. Copyright © 2016. Published by Elsevier Inc.

Canonical decomposition of magnetotelluric responses: Experiment on 1D anisotropic structures

NASA Astrophysics Data System (ADS)

Guo, Ze-qiu; Wei, Wen-bo; Ye, Gao-feng; Jin, Sheng; Jing, Jian-en

2015-08-01

Horizontal electrical heterogeneity of subsurface earth is mostly originated from structural complexity and electrical anisotropy, and local near-surface electrical heterogeneity will severely distort regional electromagnetic responses. Conventional distortion analyses for magnetotelluric soundings are primarily physical decomposition methods with respect to isotropic models, which mostly presume that the geoelectric distribution of geological structures is of local and regional patterns represented by 3D/2D models. Due to the widespread anisotropy of earth media, the confusion between 1D anisotropic responses and 2D isotropic responses, and the defects of physical decomposition methods, we propose to conduct modeling experiments with canonical decomposition in terms of 1D layered anisotropic models, and the method is one of the mathematical decomposition methods based on eigenstate analyses differentiated from distortion analyses, which can be used to recover electrical information such as strike directions, and maximum and minimum conductivity. We tested this method with numerical simulation experiments on several 1D synthetic models, which turned out that canonical decomposition is quite effective to reveal geological anisotropic information. Finally, for the background of anisotropy from previous study by geological and seismological methods, canonical decomposition is applied to real data acquired in North China Craton for 1D anisotropy analyses, and the result shows that, with effective modeling and cautious interpretation, canonical decomposition could be another good method to detect anisotropy of geological media.

A novel anisotropic inversion approach for magnetotelluric data from subsurfaces with orthogonal geoelectric strike directions

NASA Astrophysics Data System (ADS)

Schmoldt, Jan-Philipp; Jones, Alan G.

2013-12-01

The key result of this study is the development of a novel inversion approach for cases of orthogonal, or close to orthogonal, geoelectric strike directions at different depth ranges, for example, crustal and mantle depths. Oblique geoelectric strike directions are a well-known issue in commonly employed isotropic 2-D inversion of MT data. Whereas recovery of upper (crustal) structures can, in most cases, be achieved in a straightforward manner, deriving lower (mantle) structures is more challenging with isotropic 2-D inversion in the case of an overlying region (crust) with different geoelectric strike direction. Thus, investigators may resort to computationally expensive and more limited 3-D inversion in order to derive the electric resistivity distribution at mantle depths. In the novel approaches presented in this paper, electric anisotropy is used to image 2-D structures in one depth range, whereas the other region is modelled with an isotropic 1-D or 2-D approach, as a result significantly reducing computational costs of the inversion in comparison with 3-D inversion. The 1- and 2-D versions of the novel approach were tested using a synthetic 3-D subsurface model with orthogonal strike directions at crust and mantle depths and their performance was compared to results of isotropic 2-D inversion. Structures at crustal depths were reasonably well recovered by all inversion approaches, whereas recovery of mantle structures varied significantly between the different approaches. Isotropic 2-D inversion models, despite decomposition of the electric impedance tensor and using a wide range of inversion parameters, exhibited severe artefacts thereby confirming the requirement of either an enhanced or a higher dimensionality inversion approach. With the anisotropic 1-D inversion approach, mantle structures of the synthetic model were recovered reasonably well with anisotropy values parallel to the mantle strike direction (in this study anisotropy was assigned to the mantle region), indicating applicability of the novel approach for basic subsurface cases. For the more complex subsurface cases, however, the anisotropic 1-D inversion approach is likely to yield implausible models of the electric resistivity distribution due to inapplicability of the 1-D approximation. Owing to the higher number of degrees of freedom, the anisotropic 2-D inversion approach can cope with more complex subsurface cases and is the recommended tool for real data sets recorded in regions with orthogonal geoelectric strike directions.

Nearside-farside, local angular momentum and resummation theories: Useful tools for understanding the dynamics of complex-mode reactions

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

Hankel, Marlies, E-mail: m.hankel@uq.edu.au, E-mail: j.n.l.connor@manchester.ac.uk; Connor, J. N. L., E-mail: m.hankel@uq.edu.au, E-mail: j.n.l.connor@manchester.ac.uk

2015-07-15

A valuable tool for understanding the dynamics of direct reactions is Nearside-Farside (NF) scattering theory. It makes a decomposition of the (resummed) partial wave series for the scattering amplitude, both for the differential cross section (DCS) and the Local Angular Momentum (LAM). This paper makes the first combined application of these techniques to complex-mode reactions. We ask if NF theory is a useful tool for their identification, in particular, can it distinguish complex-mode from direct-mode reactions? We also ask whether NF theory can identify NF interference oscillations in the full DCSs of complex-mode reactions. Our investigation exploits the fact thatmore » accurate quantum scattering matrix elements have recently become available for complex-mode reactions. We first apply NF theory to two simple models for the scattering amplitude of a complex-mode reaction: One involves a single Legendre polynomial; the other involves a single Legendre function of the first kind, whose form is suggested by complex angular momentum theory. We then study, at fixed translational energies, four state-to-state complex-mode reactions. They are: S({sup 1}D) + HD → SH + D, S({sup 1}D) + DH → SD + H, N({sup 2}D) +H{sub 2} → NH + H, and H{sup +} + D{sub 2} → HD + D{sup +}. We compare the NF results for the DCSs and LAMs with those for a state-to-state direct reaction, namely, F + H{sub 2} → FH + H. We demonstrate that NF theory is a valuable tool for identifying and analyzing the dynamics of complex-mode reactions.« less

Application of FDA-Approved Memantine and Newer NitroMemantine Derivatives to Treat Neurological Manifestations in Rodent Models of Tuberous Sclerosis Complex

DTIC Science & Technology

2014-05-01

Memantine and Newer NitroMemantine Derivatives to Treat Neurological Manifestations in Rodent Models of Tuberous Sclerosis Complex PRINCIPAL...Approved Memantine and Newer NitroMemantine Derivatives to Treat 5a. CONTRACT NUMBER W81XWH-13-1-0053 Neurological Manifestations in Rodent Models of...to investigate if administration of the FDA-approved drug, Memantine , an uncompetitive/fast off-rate antagonist of the N- methyl-D-aspartate-type

Comparison of Commercial Structure-From Photogrammety Software Used for Underwater Three-Dimensional Modeling of Coral Reef Environments

NASA Astrophysics Data System (ADS)

Burns, J. H. R.; Delparte, D.

2017-02-01

Structural complexity in ecosystems creates an assortment of microhabitat types and has been shown to support greater diversity and abundance of associated organisms. The 3D structure of an environment also directly affects important ecological parameters such as habitat provisioning and light availability and can therefore strongly influence ecosystem function. Coral reefs are architecturally complex 3D habitats, whose structure is intrinsically linked to the ecosystem biodiversity, productivity, and function. The field of coral ecology has, however, been primarily limited to using 2-dimensional (2D) planar survey techniques for studying the physical structure of reefs. This conventional approach fails to capture or quantify the intricate structural complexity of corals that influences habitat facilitation and biodiversity. A 3-dimensional (3D) approach can obtain accurate measurements of architectural complexity, topography, rugosity, volume, and other structural characteristics that affect biodiversity and abundance of reef organisms. Structurefrom- Motion (SfM) photogrammetry is an emerging computer vision technology that provides a simple and cost-effective method for 3D reconstruction of natural environments. SfM has been used in several studies to investigate the relationship between habitat complexity and ecological processes in coral reef ecosystems. This study compared two commercial SfM software packages, Agisoft Photoscan Pro and Pix4Dmapper Pro 3.1, in order to assess the cpaability and spatial accuracy of these programs for conducting 3D modeling of coral reef habitats at three spatial scales.

Interactions of Kid-Kis toxin-antitoxin complexes with the parD operator-promoter region of plasmid R1 are piloted by the Kis antitoxin and tuned by the stoichiometry of Kid-Kis oligomers.

PubMed

Monti, Maria C; Hernández-Arriaga, Ana M; Kamphuis, Monique B; López-Villarejo, Juan; Heck, Albert J R; Boelens, Rolf; Díaz-Orejas, Ramón; van den Heuvel, Robert H H

2007-01-01

The parD operon of Escherichia coli plasmid R1 encodes a toxin-antitoxin system, which is involved in plasmid stabilization. The toxin Kid inhibits cell growth by RNA degradation and its action is neutralized by the formation of a tight complex with the antitoxin Kis. A fascinating but poorly understood aspect of the kid-kis system is its autoregulation at the transcriptional level. Using macromolecular (tandem) mass spectrometry and DNA binding assays, we here demonstrate that Kis pilots the interaction of the Kid-Kis complex in the parD regulatory region and that two discrete Kis-binding regions are present on parD. The data clearly show that only when the Kis concentration equals or exceeds the Kid concentration a strong cooperative effect exists between strong DNA binding and Kid2-Kis2-Kid2-Kis2 complex formation. We propose a model in which transcriptional repression of the parD operon is tuned by the relative molar ratio of the antitoxin and toxin proteins in solution. When the concentration of the toxin exceeds that of the antitoxin tight Kid2-Kis2-Kid2 complexes are formed, which only neutralize the lethal activity of Kid. Upon increasing the Kis concentration, (Kid2-Kis2)n complexes repress the kid-kis operon.

Structure of the Mtb CarD/RNAP β-lobes complex reveals the molecular basis of interaction and presents a distinct DNA-binding domain for Mtb CarD.

PubMed

Gulten, Gulcin; Sacchettini, James C

2013-10-08

CarD from Mycobacterium tuberculosis (Mtb) is an essential protein shown to be involved in stringent response through downregulation of rRNA and ribosomal protein genes. CarD interacts with the β-subunit of RNAP and this interaction is vital for Mtb's survival during the persistent infection state. We have determined the crystal structure of CarD in complex with the RNAP β-subunit β1 and β2 domains at 2.1 Å resolution. The structure reveals the molecular basis of CarD/RNAP interaction, providing a basis to further our understanding of RNAP regulation by CarD. The structural fold of the CarD N-terminal domain is conserved in RNAP interacting proteins such as TRCF-RID and CdnL, and displays similar interactions to the predicted homology model based on the TRCF/RNAP β1 structure. Interestingly, the structure of the C-terminal domain, which is required for complete CarD function in vivo, represents a distinct DNA-binding fold. Copyright © 2013 Elsevier Ltd. All rights reserved.

Theoretical Modeling of the Magnetic Behavior of Thiacalix[4]arene Tetranuclear Mn(II)2Gd(III)2 and Co(II)2Eu(III)2 Complexes.

PubMed

Aldoshin, Sergey M; Sanina, Nataliya A; Palii, Andrew V; Tsukerblat, Boris S

2016-04-04

In view of a wide perspective of 3d-4f complexes in single-molecule magnetism, here we propose an explanation of the magnetic behavior of the two thiacalix[4]arene tetranuclear heterometallic complexes Mn(II)2Gd(III)2 and Co(II)2Eu(III)2. The energy pattern of the Mn(II)2Gd(III)2 complex evaluated in the framework of the isotropic exchange model exhibits a rotational band of the low-lying spin excitations within which the Landé intervals are affected by the biquadratic spin-spin interactions. The nonmonotonic temperature dependence of the χT product observed for the Mn(II)2Gd(III)2 complex is attributed to the competitive influence of the ferromagnetic Mn-Gd and antiferromagnetic Mn-Mn exchange interactions, the latter being stronger (J(Mn, Mn) = -1.6 cm(-1), Js(Mn, Gd) = 0.8 cm(-1), g = 1.97). The model for the Co(II)2Eu(III)2 complex includes uniaxial anisotropy of the seven-coordinate Co(II) ions and an isotropic exchange interaction in the Co(II)2 pair, while the Eu(III) ions are diamagnetic in their ground states. Best-fit analysis of χT versus T showed that the anisotropic contribution (arising from a large zero-field splitting in Co(II) ions) dominates (weak-exchange limit) in the Co(II)2Eu(III)2 complex (D = 20.5 cm(-1), J = -0.4 cm(-1), gCo = 2.22). This complex is concluded to exhibit an easy plane of magnetization (arising from the Co(II) pair). It is shown that the low-lying part of the spectrum can be described by a highly anisotropic effective spin-(1)/2 Hamiltonian that is deduced for the Co(II)2 pair in the weak-exchange limit.

Optical Coherence Tomography Noise Reduction Using Anisotropic Local Bivariate Gaussian Mixture Prior in 3D Complex Wavelet Domain.

PubMed

Rabbani, Hossein; Sonka, Milan; Abramoff, Michael D

2013-01-01

In this paper, MMSE estimator is employed for noise-free 3D OCT data recovery in 3D complex wavelet domain. Since the proposed distribution for noise-free data plays a key role in the performance of MMSE estimator, a priori distribution for the pdf of noise-free 3D complex wavelet coefficients is proposed which is able to model the main statistical properties of wavelets. We model the coefficients with a mixture of two bivariate Gaussian pdfs with local parameters which are able to capture the heavy-tailed property and inter- and intrascale dependencies of coefficients. In addition, based on the special structure of OCT images, we use an anisotropic windowing procedure for local parameters estimation that results in visual quality improvement. On this base, several OCT despeckling algorithms are obtained based on using Gaussian/two-sided Rayleigh noise distribution and homomorphic/nonhomomorphic model. In order to evaluate the performance of the proposed algorithm, we use 156 selected ROIs from 650 × 512 × 128 OCT dataset in the presence of wet AMD pathology. Our simulations show that the best MMSE estimator using local bivariate mixture prior is for the nonhomomorphic model in the presence of Gaussian noise which results in an improvement of 7.8 ± 1.7 in CNR.

Modeling of methanol decomposition on Pt/CeO2/ZrO2 catalyst in a packed bed microreactor

NASA Astrophysics Data System (ADS)

Pohar, Andrej; Belavič, Darko; Dolanc, Gregor; Hočevar, Stanko

2014-06-01

Methanol decomposition on Pt/CeO2/ZrO2 catalyst is studied inside a packed bed microreactor in the temperature range of 300-380 °C. The microreactor is fabricated using low-temperature co-fired ceramic (LTCC) technology, which is well suited for the production of relatively complex three-dimensional structures. It is packed with 2 wt% Pt-CeO2 catalyst, which is deposited onto ZrO2 spherical particles. A 1D mathematical model, which incorporates diffusion, convection and mass transfer through the boundary layer to the catalyst particles, as well as a 3D computational fluid dynamics model, are developed to describe the methanol decomposition process inside the packed bed. The microreactor exhibits reliable operation and no catalyst deactivation was observed during three months of experimentation. A comparison between the 1D mathematical model and the 3D model, considering the full 3D geometry of the microreactor is made and the differences between the models are identified and evaluated.

In situ magnetic separation of antibody fragments from Escherichia coli in complex media

PubMed Central

2013-01-01

Background In situ magnetic separation (ISMS) has emerged as a powerful tool to overcome process constraints such as product degradation or inhibition of target production. In the present work, an integrated ISMS process was established for the production of his-tagged single chain fragment variable (scFv) D1.3 antibodies (“D1.3”) produced by E. coli in complex media. This study investigates the impact of ISMS on the overall product yield as well as its biocompatibility with the bioprocess when metal-chelate and triazine-functionalized magnetic beads were used. Results Both particle systems are well suited for separation of D1.3 during cultivation. While the triazine beads did not negatively impact the bioprocess, the application of metal-chelate particles caused leakage of divalent copper ions in the medium. After the ISMS step, elevated copper concentrations above 120 mg/L in the medium negatively influenced D1.3 production. Due to the stable nature of the model protein scFv D1.3 in the biosuspension, the application of ISMS could not increase the overall D1.3 yield as was shown by simulation and experiments. Conclusions We could demonstrate that triazine-functionalized beads are a suitable low-cost alternative to selectively adsorb D1.3 fragments, and measured maximum loads of 0.08 g D1.3 per g of beads. Although copper-loaded metal-chelate beads did adsorb his-tagged D1.3 well during cultivation, this particle system must be optimized by minimizing metal leakage from the beads in order to avoid negative inhibitory effects on growth of the microorganisms and target production. Hereby, other types of metal chelate complexes should be tested to demonstrate biocompatibility. Such optimized particle systems can be regarded as ISMS platform technology, especially for the production of antibodies and their fragments with low stability in the medium. The proposed model can be applied to design future ISMS experiments in order to maximize the overall product yield while the amount of particles being used is minimized as well as the number of required ISMS steps. PMID:23688064

Spectroscopic investigation of new water soluble Mn(II)(2) and Mg(II)(2) complexes for the substrate binding models of xylose/glucose isomerases.

PubMed

Patra, Ayan; Bera, Manindranath

2014-01-30

In methanol, the reaction of stoichiometric amounts of Mn(OAc)(2)·4H(2)O and the ligand H(3)hpnbpda [H(3)hpnbpda=N,N'-bis(2-pyridylmethyl)-2-hydroxy-1,3-propanediamine-N,N'-diacetic acid] in the presence of NaOH, afforded a new water soluble dinuclear manganese(II) complex, [Mn2(hpnbpda)(μ-OAc)] (1). Similarly, the reaction of Mg(OAc)(2)·4H(2)O and the ligand H3hpnbpda in the presence of NaOH, in methanol, yielded a new water soluble dinuclear magnesium(II) complex, [Mg2(hpnbpda)(μ-OAc)(H2O)2] (2). DFT calculations have been performed for the structural optimization of complexes 1 and 2. The DFT optimized structure of complex 1 shows that two manganese(II) centers are in a distorted square pyramidal geometry, whereas the DFT optimized structure of complex 2 reveals that two magnesium(II) centers adopt a six-coordinate distorted octahedral geometry. To understand the mode of substrate binding and the mechanistic details of the active site metals in xylose/glucose isomerases (XGI), we have investigated the binding interactions of biologically important monosaccharides d-glucose and d-xylose with complexes 1 and 2, in aqueous alkaline solution by a combined approach of FTIR, UV-vis, fluorescence, and (13)C NMR spectroscopic techniques. Fluorescence spectra show the binding-induced gradual decrease in emission of complexes 1 and 2 accompanied by a significant blue shift upon increasing the concentration of sugar substrates. The binding modes of d-glucose and d-xylose with complex 2 are indicated by their characteristic coordination induced shift (CIS) values in (13)C NMR spectra for C1 and C2 carbon atoms. Copyright © 2013 Elsevier Ltd. All rights reserved.

Seeking potential anticonvulsant agents that target GABAA receptors using experimental and theoretical procedures

NASA Astrophysics Data System (ADS)

Saavedra-Vélez, Margarita Virginia; Correa-Basurto, José; Matus, Myrna H.; Gasca-Pérez, Eloy; Bello, Martiniano; Cuevas-Hernández, Roberto; García-Rodríguez, Rosa Virginia; Trujillo-Ferrara, José; Ramos-Morales, Fernando Rafael

2014-12-01

The aim of this study was to identify compounds that possess anticonvulsant activity by using a pentylenetetrazol (PTZ)-induced seizure model. Theoretical studies of a set of ligands, explored the binding affinities of the ligands for the GABAA receptor (GABAAR), including some benzodiazepines. The ligands satisfy the Lipinski rules and contain a pharmacophore core that has been previously reported to be a GABAAR activator. To select the ligands with the best physicochemical properties, all of the compounds were analyzed by quantum mechanics and the energies of the highest occupied molecular orbital and lowest unoccupied molecular orbital were determined. Docking calculations between the ligands and the GABAAR were used to identify the complexes with the highest Gibbs binding energies. The identified compound D1 (dibenzo( b,f)(1,4)diazocine-6,11(5H,12H)-dione) was synthesized, experimentally tested, and the GABAAR-D1 complex was submitted to 12-ns-long molecular dynamics (MD) simulations to corroborate the binding conformation obtained by docking techniques. MD simulations were also used to analyze the decomposition of the Gibbs binding energy of the residues involved in the stabilization of the complex. To validate our theoretical results, molecular docking and MD simulations were also performed for three reference compounds that are currently in commercial use: clonazepam (CLZ), zolpidem and eszopiclone. The theoretical results show that the GABAAR-D1, and GABAAR-CLZ complexes bind to the benzodiazepine binding site, share a similar map of binding residues, and have similar Gibbs binding energies and entropic components. Experimental studies using a PTZ-induced seizure model showed that D1 possesses similar activity to CLZ, which corroborates the predicted binding free energy identified by theoretical calculations.

Structural and functional insight into TAF1-TAF7, a subcomplex of transcription factor II D

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

Bhattacharya, Suparna; Lou, Xiaohua; Hwang, Peter

2014-07-01

Transcription factor II D (TFIID) is a multiprotein complex that nucleates formation of the basal transcription machinery. TATA binding protein-associated factors 1 and 7 (TAF1 and TAF7), two subunits of TFIID, are integral to the regulation of eukaryotic transcription initiation and play key roles in preinitiation complex (PIC) assembly. Current models suggest that TAF7 acts as a dissociable inhibitor of TAF1 histone acetyltransferase activity and that this event ensures appropriate assembly of the RNA polymerase II-mediated PIC before transcriptional initiation. Here, we report the 3D structure of a complex of yeast TAF1 with TAF7 at 2.9 Å resolution. The structuremore » displays novel architecture and is characterized by a large predominantly hydrophobic heterodimer interface and extensive cofolding of TAF subunits. There are no obvious similarities between TAF1 and known histone acetyltransferases. Instead, the surface of the TAF1–TAF7 complex contains two prominent conserved surface pockets, one of which binds selectively to an inhibitory trimethylated histone H3 mark on Lys27 in a manner that is also regulated by phosphorylation at the neighboring H3 serine. Our findings could point toward novel roles for the TAF1–TAF7 complex in regulation of PIC assembly via reading epigenetic histone marks.« less

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

Gao, X.; Patel, D.J.

The authors report on two-dimensional proton NMR studies of echinomycin complexes with the self-complementary d(A1-C2-G3-Tr) and d(T1-C2-G3-A4) duplexes in aqueous solution. The exchangeable and nonexchangeable antibiotic and nucleic acid protons in the 1 echinomycin per tetranucleotide duplex complexes have been assigned from analyses of scalar coupling and distance connectivities in two-dimensional data sets records in H/sub 2/O and D/sub 2/O solution. An analysis of the intermolecular NOE patterns for both complexes combined with large upfield imino proton and large downfield phosphorus complexation chemical shift changes demonstrates that the two quinoxaline chromophores of echinomycin bisintercalate into the minor groove surrounding themore » dC-dG step of each tetranucleotide duplex. Further, the quinoxaline rings selectively stack between A1 and C2 bases in the d(ACGT) complex and between T1 and C2 bases in the d(TCGA) complex. The intermolecular NOE patterns and the base and sugar proton chemical shifts for residues C2 and G3 are virtually identical for the d(ACGT) and d(TCGA) complexes. A large set of intermolecular contacts established from nuclear Overhauser effects (NOEs) between antibiotic and nucleic acid protons in the echinomycin-tetranucleotide complexes in solution are consistent with corresponding contacts reported for echinomycin-oligonucleotide complexes in the crystalline state. The authors demonstrate that the G x G base pairs adopt Watson-Crick pairing in both d(ACGT) and d(TCGA) complexes in solution. By contrast, the A1 x T4 base pairs adopt Hoogsteen pairing for the echinomycin-d(A1-C2-G3-Tr) complex while the T1 x A4 base pairs adopt Watson-Crick pairing for the echinomycin-d(T1-C2-G3-A4) complex in aqueous solution. These results emphasize the role of sequence in discriminating between Watson-Crick and Hoogsteen pairs at base pairs flanking the echinomycin bisintercalation site in solution.« less

Recent developments and assessment of a three-dimensional PBL parameterization for improved wind forecasting over complex terrain

NASA Astrophysics Data System (ADS)

Kosovic, B.; Jimenez, P. A.; Haupt, S. E.; Martilli, A.; Olson, J.; Bao, J. W.

2017-12-01

At present, the planetary boundary layer (PBL) parameterizations available in most numerical weather prediction (NWP) models are one-dimensional. One-dimensional parameterizations are based on the assumption of horizontal homogeneity. This homogeneity assumption is appropriate for grid cell sizes greater than 10 km. However, for mesoscale simulations of flows in complex terrain with grid cell sizes below 1 km, the assumption of horizontal homogeneity is violated. Applying a one-dimensional PBL parameterization to high-resolution mesoscale simulations in complex terrain could result in significant error. For high-resolution mesoscale simulations of flows in complex terrain, we have therefore developed and implemented a three-dimensional (3D) PBL parameterization in the Weather Research and Forecasting (WRF) model. The implementation of the 3D PBL scheme is based on the developments outlined by Mellor and Yamada (1974, 1982). Our implementation in the Weather Research and Forecasting (WRF) model uses a pure algebraic model (level 2) to diagnose the turbulent fluxes. To evaluate the performance of the 3D PBL model, we use observations from the Wind Forecast Improvement Project 2 (WFIP2). The WFIP2 field study took place in the Columbia River Gorge area from 2015-2017. We focus on selected cases when physical phenomena of significance for wind energy applications such as mountain waves, topographic wakes, and gap flows were observed. Our assessment of the 3D PBL parameterization also considers a large-eddy simulation (LES). We carried out a nested LES with grid cell sizes of 30 m and 10 m covering a large fraction of the WFIP2 study area. Both LES domains were discretized using 6000 x 3000 x 200 grid cells in zonal, meridional, and vertical direction, respectively. The LES results are used to assess the relative magnitude of horizontal gradients of turbulent stresses and fluxes in comparison to vertical gradients. The presentation will highlight the advantages of the 3D PBL scheme in regions of complex terrain.

Copper(II) complex with 6-methylpyridine-2-carboxyclic acid: Experimental and computational study on the XRD, FT-IR and UV-Vis spectra, refractive index, band gap and NLO parameters

NASA Astrophysics Data System (ADS)

Altürk, Sümeyye; Avcı, Davut; Başoğlu, Adil; Tamer, Ömer; Atalay, Yusuf; Dege, Necmi

2018-02-01

Crystal structure of the synthesized copper(II) complex with 6-methylpyridine-2-carboxylic acid, [Cu(6-Mepic)2·H2O]·H2O, was determined by XRD, FT-IR and UV-Vis spectroscopic techniques. Furthermore, the geometry optimization, harmonic vibration frequencies for the Cu(II) complex were carried out by using Density Functional Theory calculations with HSEh1PBE/6-311G(d,p)/LanL2DZ level. Electronic absorption wavelengths were obtained by using TD-DFT/HSEh1PBE/6-311G(d,p)/LanL2DZ level with CPCM model and major contributions were determined via Swizard/Chemissian program. Additionally, the refractive index, linear optical (LO) and non-nonlinear optical (NLO) parameters of the Cu(II) complex were calculated at HSEh1PBE/6-311G(d,p) level. The experimental and computed small energy gap shows the charge transfer in the Cu(II) complex. Finally, the hyperconjugative interactions and intramolecular charge transfer (ICT) were studied by performing of natural bond orbital (NBO) analysis.

Copper(II) complex with 6-methylpyridine-2-carboxyclic acid: Experimental and computational study on the XRD, FT-IR and UV-Vis spectra, refractive index, band gap and NLO parameters.

PubMed

Altürk, Sümeyye; Avcı, Davut; Başoğlu, Adil; Tamer, Ömer; Atalay, Yusuf; Dege, Necmi

2018-02-05

Crystal structure of the synthesized copper(II) complex with 6-methylpyridine-2-carboxylic acid, [Cu(6-Mepic) 2 ·H 2 O]·H 2 O, was determined by XRD, FT-IR and UV-Vis spectroscopic techniques. Furthermore, the geometry optimization, harmonic vibration frequencies for the Cu(II) complex were carried out by using Density Functional Theory calculations with HSEh1PBE/6-311G(d,p)/LanL2DZ level. Electronic absorption wavelengths were obtained by using TD-DFT/HSEh1PBE/6-311G(d,p)/LanL2DZ level with CPCM model and major contributions were determined via Swizard/Chemissian program. Additionally, the refractive index, linear optical (LO) and non-nonlinear optical (NLO) parameters of the Cu(II) complex were calculated at HSEh1PBE/6-311G(d,p) level. The experimental and computed small energy gap shows the charge transfer in the Cu(II) complex. Finally, the hyperconjugative interactions and intramolecular charge transfer (ICT) were studied by performing of natural bond orbital (NBO) analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Numerical analysis of one-dimensional temperature data for groundwater/surface-water exchange with 1DTempPro

NASA Astrophysics Data System (ADS)

Voytek, E. B.; Drenkelfuss, A.; Day-Lewis, F. D.; Healy, R. W.; Lane, J. W.; Werkema, D. D.

2012-12-01

Temperature is a naturally occurring tracer, which can be exploited to infer the movement of water through the vadose and saturated zones, as well as the exchange of water between aquifers and surface-water bodies, such as estuaries, lakes, and streams. One-dimensional (1D) vertical temperature profiles commonly show thermal amplitude attenuation and increasing phase lag of diurnal or seasonal temperature variations with propagation into the subsurface. This behavior is described by the heat-transport equation (i.e., the convection-conduction-dispersion equation), which can be solved analytically in 1D under certain simplifying assumptions (e.g., sinusoidal or steady-state boundary conditions and homogeneous hydraulic and thermal properties). Analysis of 1D temperature profiles using analytical models provides estimates of vertical groundwater/surface-water exchange. The utility of these estimates can be diminished when the model assumptions are violated, as is common in field applications. Alternatively, analysis of 1D temperature profiles using numerical models allows for consideration of more complex and realistic boundary conditions. However, such analyses commonly require model calibration and the development of input files for finite-difference or finite-element codes. To address the calibration and input file requirements, a new computer program, 1DTempPro, is presented that facilitates numerical analysis of vertical 1D temperature profiles. 1DTempPro is a graphical user interface (GUI) to the USGS code VS2DH, which numerically solves the flow- and heat-transport equations. Pre- and post-processor features within 1DTempPro allow the user to calibrate VS2DH models to estimate groundwater/surface-water exchange and hydraulic conductivity in cases where hydraulic head is known. This approach improves groundwater/ surface-water exchange-rate estimates for real-world data with complexities ill-suited for examination with analytical methods. Additionally, the code allows for time-varying temperature and hydraulic boundary conditions. Here, we present the approach and include examples for several datasets from stream/aquifer systems.

CD1d expression on chronic lymphocytic leukemia B cells affects disease progression and induces T cell skewing in CD8 positive and CD4CD8 double negative T cells.

PubMed

Zaborsky, Nadja; Gassner, Franz Josef; Asslaber, Daniela; Reinthaler, Petra; Denk, Ursula; Flenady, Sabine; Hofbauer, Josefina Piñón; Danner, Barbara; Rebhandl, Stefan; Harrer, Andrea; Geisberger, Roland; Greil, Richard; Egle, Alexander

2016-08-02

Chronic lymphocytic leukemia develops within a complex network driven by genetic mutations and microenvironmental interactions. Among the latter a complex interplay with the immune system is established by the clone. Next to a proposed recruitment of support from T and myeloid cells, potential anti-CLL immune reactions need to be subverted. By using TCL1 mice as a CLL model, we show that TCR-Vβ7+ NK1.1+ T cells are overrepresented in this disease model and constitute a main subset of peripheral CD3+ cells with biased TCR usage, showing that these cells account for a major part for T cell skewing in TCL1 mice. Moreover, we show that overrepresentation is dependent on CD1d expression in TCL1 mice, implicating that these cells belong to a NKT-like cell fraction which are restricted to antigen presented by the MHC-like surface marker CD1d. Accordingly, we observed a high fraction of CD161+ cells within overrepresented T cells in CLL patients and we found downregulation of CD1d on the surface of CLL cells, both in TCL1 mice and patients. Finally, we show that in TCL1 mice, CD1d deficiency resulted in shortened overall survival. Our results point to an interaction between CLL and CD161+ T cells that may represent a novel therapeutic target for immune modulation.

Three perspectives on complexity: entropy, compression, subsymmetry

NASA Astrophysics Data System (ADS)

Nagaraj, Nithin; Balasubramanian, Karthi

2017-12-01

There is no single universally accepted definition of `Complexity'. There are several perspectives on complexity and what constitutes complex behaviour or complex systems, as opposed to regular, predictable behaviour and simple systems. In this paper, we explore the following perspectives on complexity: effort-to-describe (Shannon entropy H, Lempel-Ziv complexity LZ), effort-to-compress (ETC complexity) and degree-of-order (Subsymmetry or SubSym). While Shannon entropy and LZ are very popular and widely used, ETC is relatively a new complexity measure. In this paper, we also propose a novel normalized complexity measure SubSym based on the existing idea of counting the number of subsymmetries or palindromes within a sequence. We compare the performance of these complexity measures on the following tasks: (A) characterizing complexity of short binary sequences of lengths 4 to 16, (B) distinguishing periodic and chaotic time series from 1D logistic map and 2D Hénon map, (C) analyzing the complexity of stochastic time series generated from 2-state Markov chains, and (D) distinguishing between tonic and irregular spiking patterns generated from the `Adaptive exponential integrate-and-fire' neuron model. Our study reveals that each perspective has its own advantages and uniqueness while also having an overlap with each other.

Simulations of Seismic Wave Propagation on Mars

NASA Astrophysics Data System (ADS)

Bozdağ, Ebru; Ruan, Youyi; Metthez, Nathan; Khan, Amir; Leng, Kuangdai; van Driel, Martin; Wieczorek, Mark; Rivoldini, Attilio; Larmat, Carène S.; Giardini, Domenico; Tromp, Jeroen; Lognonné, Philippe; Banerdt, Bruce W.

2017-10-01

We present global and regional synthetic seismograms computed for 1D and 3D Mars models based on the spectral-element method. For global simulations, we implemented a radially-symmetric Mars model with a 110 km thick crust (Sohl and Spohn in J. Geophys. Res., Planets 102(E1):1613-1635, 1997). For this 1D model, we successfully benchmarked the 3D seismic wave propagation solver SPECFEM3D_GLOBE (Komatitsch and Tromp in Geophys. J. Int. 149(2):390-412, 2002a; 150(1):303-318, 2002b) against the 2D axisymmetric wave propagation solver AxiSEM (Nissen-Meyer et al. in Solid Earth 5(1):425-445, 2014) at periods down to 10 s. We also present higher-resolution body-wave simulations with AxiSEM down to 1 s in a model with a more complex 1D crust, revealing wave propagation effects that would have been difficult to interpret based on ray theory. For 3D global simulations based on SPECFEM3D_GLOBE, we superimposed 3D crustal thickness variations capturing the distinct crustal dichotomy between Mars' northern and southern hemispheres, as well as topography, ellipticity, gravity, and rotation. The global simulations clearly indicate that the 3D crust speeds up body waves compared to the reference 1D model, whereas it significantly changes surface waveforms and their dispersive character depending on its thickness. We also perform regional simulations with the solver SES3D (Fichtner et al. Geophys. J. Int. 179:1703-1725, 2009) based on 3D crustal models derived from surface composition, thereby addressing the effects of various distinct crustal features down to 2 s. The regional simulations confirm the strong effects of crustal variations on waveforms. We conclude that the numerical tools are ready for examining more scenarios, including various other seismic models and sources.

C–H and O 2 activation at a Pt(II) center enabled by a novel sulfonated CNN pincer ligand

DOE PAGES

Watts, David; Wang, Daoyong; Adelberg, Mackenzie; ...

2016-09-21

A novel sulfonated CNN pincer ligand has been designed to support CH and O 2 activation at a Pt(II) center. The derived cycloplatinated aqua complex 7 was found to be one of the most active reported homogeneous Pt catalysts for H/D exchange between studied arenes (benzene, benzene-d 6, toluene-d 8, p-xylene, and mesitylene) and 2,2,2-trifluoroethanol (TFE) or 2,2,2-trifluoroethanol-d; the TON for C 6D 6 as a substrate is >250 after 48 h at 80 °C. The reaction is very selective; no benzylic CH bond activation was observed. The per-CH-bond reactivity diminishes in the series benzene (19) > toluene ( p-CH:more » m-CH: o-CH = 1:0.9:0.2) > xylene (2.9) > mesitylene (1.1). The complex 7 reacts slowly in TFE solutions under ambient light but not in the dark with O 2 to selectively produce a Pt(IV) trifluoroethoxo derivative. The H/D exchange reaction kinetics and results of the DFT study suggest that complex 7, and not its TFE derivatives, is the major species responsible for the arene CH bond activation. Lastly, the reaction deuterium kinetic isotope effect, k H/k D = 1.7, the reaction selectivity, and reaction kinetics modeling suggest that the CH bond cleavage step is rate-determining.« less

Autophagy in Dictyostelium: Mechanisms, regulation and disease in a simple biomedical model.

PubMed

Mesquita, Ana; Cardenal-Muñoz, Elena; Dominguez, Eunice; Muñoz-Braceras, Sandra; Nuñez-Corcuera, Beatriz; Phillips, Ben A; Tábara, Luis C; Xiong, Qiuhong; Coria, Roberto; Eichinger, Ludwig; Golstein, Pierre; King, Jason S; Soldati, Thierry; Vincent, Olivier; Escalante, Ricardo

2017-01-02

Autophagy is a fast-moving field with an enormous impact on human health and disease. Understanding the complexity of the mechanism and regulation of this process often benefits from the use of simple experimental models such as the social amoeba Dictyostelium discoideum. Since the publication of the first review describing the potential of D. discoideum in autophagy, significant advances have been made that demonstrate both the experimental advantages and interest in using this model. Since our previous review, research in D. discoideum has shed light on the mechanisms that regulate autophagosome formation and contributed significantly to the study of autophagy-related pathologies. Here, we review these advances, as well as the current techniques to monitor autophagy in D. discoideum. The comprehensive bioinformatics search of autophagic proteins that was a substantial part of the previous review has not been revisited here except for those aspects that challenged previous predictions such as the composition of the Atg1 complex. In recent years our understanding of, and ability to investigate, autophagy in D. discoideum has evolved significantly and will surely enable and accelerate future research using this model.

Modelling of aortic aneurysm and aortic dissection through 3D printing.

PubMed

Ho, Daniel; Squelch, Andrew; Sun, Zhonghua

2017-03-01

The aim of this study was to assess if the complex anatomy of aortic aneurysm and aortic dissection can be accurately reproduced from a contrast-enhanced computed tomography (CT) scan into a three-dimensional (3D) printed model. Contrast-enhanced cardiac CT scans from two patients were post-processed and produced as 3D printed thoracic aorta models of aortic aneurysm and aortic dissection. The transverse diameter was measured at five anatomical landmarks for both models, compared across three stages: the original contrast-enhanced CT images, the stereolithography (STL) format computerised model prepared for 3D printing and the contrast-enhanced CT of the 3D printed model. For the model with aortic dissection, measurements of the true and false lumen were taken and compared at two points on the descending aorta. Three-dimensional printed models were generated with strong and flexible plastic material with successful replication of anatomical details of aortic structures and pathologies. The mean difference in transverse vessel diameter between the contrast-enhanced CT images before and after 3D printing was 1.0 and 1.2 mm, for the first and second models respectively (standard deviation: 1.0 mm and 0.9 mm). Additionally, for the second model, the mean luminal diameter difference between the 3D printed model and CT images was 0.5 mm. Encouraging results were achieved with regards to reproducing 3D models depicting aortic aneurysm and aortic dissection. Variances in vessel diameter measurement outside a standard deviation of 1 mm tolerance indicate further work is required into the assessment and accuracy of 3D model reproduction. © 2017 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.

Functional CD1d and/or NKT cell invariant chain transcript in horse, pig, African elephant and guinea pig, but not in ruminants.

PubMed

Looringh van Beeck, Frank A; Reinink, Peter; Hermsen, Roel; Zajonc, Dirk M; Laven, Marielle J; Fun, Axel; Troskie, Milana; Schoemaker, Nico J; Morar, Darshana; Lenstra, Johannes A; Vervelde, Lonneke; Rutten, Victor P M G; van Eden, Willem; Van Rhijn, Ildiko

2009-04-01

CD1d-restricted invariant natural killer T cells (NKT cells) have been well characterized in humans and mice, but it is unknown whether they are present in other species. Here we describe the invariant TCR alpha chain and the full length CD1d transcript of pig and horse. Molecular modeling predicts that porcine (po) invariant TCR alpha chain/poCD1d/alpha-GalCer and equine (eq) invariant TCR alpha chain/eqCD1d/alpha-GalCer form complexes that are highly homologous to the human complex. Since a prerequisite for the presence of NKT cells is the expression of CD1d protein, we performed searches for CD1D genes and CD1d transcripts in multiple species. Previously, cattle and guinea pig have been suggested to lack CD1D genes. The CD1D genes of European taurine cattle (Bos taurus) are known to be pseudogenes because of disrupting mutations in the start codon and in the donor splice site of the first intron. Here we show that the same mutations are found in six other ruminants: African buffalo, sheep, bushbuck, bongo, N'Dama cattle, and roe deer. In contrast, intact CD1d transcripts were found in guinea pig, African elephant, horse, rabbit, and pig. Despite the discovery of a highly homologous NKT/CD1d system in pig and horse, our data suggest that functional CD1D and CD1d-restricted NKT cells are not universally present in mammals.

3D Bioprinting of Tissue/Organ Models.

PubMed

Pati, Falguni; Gantelius, Jesper; Svahn, Helene Andersson

2016-04-04

In vitro tissue/organ models are useful platforms that can facilitate systematic, repetitive, and quantitative investigations of drugs/chemicals. The primary objective when developing tissue/organ models is to reproduce physiologically relevant functions that typically require complex culture systems. Bioprinting offers exciting prospects for constructing 3D tissue/organ models, as it enables the reproducible, automated production of complex living tissues. Bioprinted tissues/organs may prove useful for screening novel compounds or predicting toxicity, as the spatial and chemical complexity inherent to native tissues/organs can be recreated. In this Review, we highlight the importance of developing 3D in vitro tissue/organ models by 3D bioprinting techniques, characterization of these models for evaluating their resemblance to native tissue, and their application in the prioritization of lead candidates, toxicity testing, and as disease/tumor models. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

2.5D complex resistivity modeling and inversion using unstructured grids

NASA Astrophysics Data System (ADS)

Xu, Kaijun; Sun, Jie

2016-04-01

The characteristic of complex resistivity on rock and ore has been recognized by people for a long time. Generally we have used the Cole-Cole Model(CCM) to describe complex resistivity. It has been proved that the electrical anomaly of geologic body can be quantitative estimated by CCM parameters such as direct resistivity(ρ0), chargeability(m), time constant(τ) and frequency dependence(c). Thus it is very important to obtain the complex parameters of geologic body. It is difficult to approximate complex structures and terrain using traditional rectangular grid. In order to enhance the numerical accuracy and rationality of modeling and inversion, we use an adaptive finite-element algorithm for forward modeling of the frequency-domain 2.5D complex resistivity and implement the conjugate gradient algorithm in the inversion of 2.5D complex resistivity. An adaptive finite element method is applied for solving the 2.5D complex resistivity forward modeling of horizontal electric dipole source. First of all, the CCM is introduced into the Maxwell's equations to calculate the complex resistivity electromagnetic fields. Next, the pseudo delta function is used to distribute electric dipole source. Then the electromagnetic fields can be expressed in terms of the primary fields caused by layered structure and the secondary fields caused by inhomogeneities anomalous conductivity. At last, we calculated the electromagnetic fields response of complex geoelectric structures such as anticline, syncline, fault. The modeling results show that adaptive finite-element methods can automatically improve mesh generation and simulate complex geoelectric models using unstructured grids. The 2.5D complex resistivity invertion is implemented based the conjugate gradient algorithm.The conjugate gradient algorithm doesn't need to compute the sensitivity matrix but directly computes the sensitivity matrix or its transpose multiplying vector. In addition, the inversion target zones are segmented with fine grids and the background zones are segmented with big grid, the method can reduce the grid amounts of inversion, it is very helpful to improve the computational efficiency. The inversion results verify the validity and stability of conjugate gradient inversion algorithm. The results of theoretical calculation indicate that the modeling and inversion of 2.5D complex resistivity using unstructured grids are feasible. Using unstructured grids can improve the accuracy of modeling, but the large number of grids inversion is extremely time-consuming, so the parallel computation for the inversion is necessary. Acknowledgments: We thank to the support of the National Natural Science Foundation of China(41304094).

Dinuclear copper(II) complexes with {Cu2(mu-hydroxo)bis(mu-carboxylato)}+ cores and their reactions with sugar phosphate esters: A substrate binding model of fructose-1,6-bisphosphatase.

PubMed

Kato, Merii; Tanase, Tomoaki; Mikuriya, Masahiro

2006-04-03

Reactions of CuX2.nH2O with the biscarboxylate ligand XDK (H2XDK = m-xylenediamine bis(Kemp's triacid imide)) in the presence of N-donor auxiliary ligands yielded a series of dicopper(II) complexes, [Cu2(mu-OH)(XDK)(L)2]X (L = N,N,N',N'-tetramethylethylenediamine (tetmen), X = NO3 (1a), Cl (1b); L = N,N,N'-trimethylethylenediamine (tmen), X = NO3 (2a), Cl (2b); L =2,2'-bipyridine (bpy), X = NO3 (3); L = 1,10-phenanthroline (phen), X = NO3 (4); L = 4,4'-dimethyl-2,2'-bipyridine (Me2bpy), X = NO3 (5); L = 4-methyl-1,10-phenanthroline (Mephen), X = NO3 (6)). Complexes 1-6 were characterized by X-ray crystallography (Cu...Cu = 3.1624(6)-3.2910(4) A), and the electrochemical and magnetic properties were also examined. Complexes 3 and 4 readily reacted with diphenyl phosphoric acid (HDPP) or bis(4-nitrophenyl) phosphoric acid (HBNPP) to give [Cu2(mu-phosphate)(XDK)(L)2]NO3 (L = bpy, phosphate = DPP (11); L = phen, phosphate = DPP (12), BNPP (13)), where the phsophate diester bridges the two copper ions in a mu-1,3-O,O' bidentate fashion (Cu...Cu = 4.268(3)-4.315(1) A). Complexes 4 and 6 with phen and Mephen have proven to be good precursors to accommodate a series of sugar monophosphate esters (Sugar-P) onto the biscarboxylate-bridged dicopper centers, yielding [Cu2(mu-Sugar-P)(XDK)(L)2] (Sugar-P = alpha-D-Glc-1-P (23a and b), D-Glc-6-P (24a and b), D-Man-6-P (25a), D-Fru-6-P (26a and b); L = phen (a), Mephen (b)) and [Cu2(mu-Gly-n-P)(XDK)(Mephen)2] (Gly-n-P = glycerol n-phosphate; n = 2 (21), 3 (22)), where Glc, Man, and Fru are glucose, mannose, and fructose, respectively. The structure of [Cu2(mu-MNPP)(XDK)(phen)2(CH3OH)] (20) was characterized as a reference compound (H2MNPP = 4-nitrophenyl phosphoric acid). Complexes 4 and 6 also reacted with d-fructose 1,6-bisphosphate (D-Fru-1,6-P2) to afford the tetranuclear copper(II) complexes formulated as [Cu4(mu-D-Fru-1,6-P2)(XDK)2(L)4] (L = phen (27a), Mephen (27b)). The detailed structure of 27a was determined by X-ray crystallography to involve two different tetranuclear complexes with alpha- and beta-anomers of D-Fru-1,6-P2, [Cu4(mu-alpha-D-Fru-1,6-P2)(XDK)2(phen)4] and [Cu4(mu-beta-D-Fru-1,6-P2)(XDK)2(phen)4], in which the D-Fru-1,6-P2 tetravalent anion bridges the two [Cu2(XDK)(phen)2]2+ units through the C1 and C6 phosphate groups in a mu-1,3-O,O' bidentate fashion (Cu...Cu = 4.042(2)-4.100(2) A). Notably, the structure with alpha-D-Fru-1,6-P2 demonstrated the presence of a strong hydrogen bond between the C2 hydroxyl group and the C1 phosphate oxygen atom, which may support the previously proposed catalytic mechanism in the active site of fructose-1,6-bisphosphatase.

Applications of Computer Technology in Complex Craniofacial Reconstruction.

PubMed

Day, Kristopher M; Gabrick, Kyle S; Sargent, Larry A

2018-03-01

To demonstrate our use of advanced 3-dimensional (3D) computer technology in the analysis, virtual surgical planning (VSP), 3D modeling (3DM), and treatment of complex congenital and acquired craniofacial deformities. We present a series of craniofacial defects treated at a tertiary craniofacial referral center utilizing state-of-the-art 3D computer technology. All patients treated at our center using computer-assisted VSP, prefabricated custom-designed 3DMs, and/or 3D printed custom implants (3DPCI) in the reconstruction of craniofacial defects were included in this analysis. We describe the use of 3D computer technology to precisely analyze, plan, and reconstruct 31 craniofacial deformities/syndromes caused by: Pierre-Robin (7), Treacher Collins (5), Apert's (2), Pfeiffer (2), Crouzon (1) Syndromes, craniosynostosis (6), hemifacial microsomia (2), micrognathia (2), multiple facial clefts (1), and trauma (3). In select cases where the available bone was insufficient for skeletal reconstruction, 3DPCIs were fabricated using 3D printing. We used VSP in 30, 3DMs in all 31, distraction osteogenesis in 16, and 3DPCIs in 13 cases. Utilizing these technologies, the above complex craniofacial defects were corrected without significant complications and with excellent aesthetic results. Modern 3D technology allows the surgeon to better analyze complex craniofacial deformities, precisely plan surgical correction with computer simulation of results, customize osteotomies, plan distractions, and print 3DPCI, as needed. The use of advanced 3D computer technology can be applied safely and potentially improve aesthetic and functional outcomes after complex craniofacial reconstruction. These techniques warrant further study and may be reproducible in various centers of care.

Understanding Spatially Complex Segmental and Branch Anatomy Using 3D Printing: Liver, Lung, Prostate, Coronary Arteries, and Circle of Willis.

PubMed

Javan, Ramin; Herrin, Douglas; Tangestanipoor, Ardalan

2016-09-01

Three-dimensional (3D) manufacturing is shaping personalized medicine, in which radiologists can play a significant role, be it as consultants to surgeons for surgical planning or by creating powerful visual aids for communicating with patients, physicians, and trainees. This report illustrates the steps in development of custom 3D models that enhance the understanding of complex anatomy. We graphically designed 3D meshes or modified imported data from cross-sectional imaging to develop physical models targeted specifically for teaching complex segmental and branch anatomy. The 3D printing itself is easily accessible through online commercial services, and the models are made of polyamide or gypsum. Anatomic models of the liver, lungs, prostate, coronary arteries, and the Circle of Willis were created. These models have advantages that include customizable detail, relative low cost, full control of design focusing on subsegments, color-coding potential, and the utilization of cross-sectional imaging combined with graphic design. Radiologists have an opportunity to serve as leaders in medical education and clinical care with 3D printed models that provide beneficial interaction with patients, clinicians, and trainees across all specialties by proactively taking on the educator's role. Complex models can be developed to show normal anatomy or common pathology for medical educational purposes. There is a need for randomized trials, which radiologists can design, to demonstrate the utility and effectiveness of 3D printed models for teaching simple and complex anatomy, simulating interventions, measuring patient satisfaction, and improving clinical care. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

"Let's get physical": advantages of a physical model over 3D computer models and textbooks in learning imaging anatomy.

PubMed

Preece, Daniel; Williams, Sarah B; Lam, Richard; Weller, Renate

2013-01-01

Three-dimensional (3D) information plays an important part in medical and veterinary education. Appreciating complex 3D spatial relationships requires a strong foundational understanding of anatomy and mental 3D visualization skills. Novel learning resources have been introduced to anatomy training to achieve this. Objective evaluation of their comparative efficacies remains scarce in the literature. This study developed and evaluated the use of a physical model in demonstrating the complex spatial relationships of the equine foot. It was hypothesized that the newly developed physical model would be more effective for students to learn magnetic resonance imaging (MRI) anatomy of the foot than textbooks or computer-based 3D models. Third year veterinary medicine students were randomly assigned to one of three teaching aid groups (physical model; textbooks; 3D computer model). The comparative efficacies of the three teaching aids were assessed through students' abilities to identify anatomical structures on MR images. Overall mean MRI assessment scores were significantly higher in students utilizing the physical model (86.39%) compared with students using textbooks (62.61%) and the 3D computer model (63.68%) (P < 0.001), with no significant difference between the textbook and 3D computer model groups (P = 0.685). Student feedback was also more positive in the physical model group compared with both the textbook and 3D computer model groups. Our results suggest that physical models may hold a significant advantage over alternative learning resources in enhancing visuospatial and 3D understanding of complex anatomical architecture, and that 3D computer models have significant limitations with regards to 3D learning. © 2013 American Association of Anatomists.

Influence of topographic complexity on solar insolation estimates for the Colorado River, Grand Canyon, AZ

USGS Publications Warehouse

Yard, M.D.; Bennett, G.E.; Mietz, S.N.; Coggins, L.G.; Stevens, L.E.; Hueftle, S.; Blinn, D.W.

2005-01-01

Rugged topography along the Colorado River in Glen and Grand Canyons, exemplifies features common to canyon-bound streams and rivers of the arid southwest. Physical relief influences regulated river systems, especially those that are altered, and have become partially reliant on aquatic primary production. We measured and modeled instantaneous solar flux in a topographically complex environment to determine where differences in daily, seasonal and annual solar insolation occurred in this river system. At a system-wide scale, topographic complexity generates a spatial and temporal mosaic of varying solar insolation. This solar variation is a predictable consequence of channel orientation, geomorphology, elevation angles and viewshed. Modeled estimates for clear conditions corresponded closely with observed measurements for both instantaneous photosynthetic photon flux density (PPFD: ??mol m-2 s-1) and daily insolation levels (relative error 2.3%, CI ??0.45, S.D. 0.3, n = 29,813). Mean annual daily insolation levels system-wide were estimated to be 36 mol m-2 d -1 (17.5 S.D.), and seasonally varied on average from 13.4-57.4 mol m-2 d-1, for winter and summer, respectively. In comparison to identical areas lacking topographic effect (idealized plane), mean daily insolation levels were reduced by 22% during summer, and as much as 53% during winter. Depending on outlying topography, canyon bound regions having east-west (EW) orientations had higher seasonal variation, averaging from 8.1 to 61.4 mol m-2 d-1, for winter and summer, respectively. For EW orientations, 70% of mid-channel sites were obscured from direct incidence during part of the year; and of these sites, average diffuse light conditions persisted for 19.3% of the year (70.5 days), and extended upwards to 194 days. This predictive model has provided an initial quantitative step to estimate and determine the importance of autotrophic production for this ecosystem, as well as a broader application for other canyon systems. ?? 2004 Published by Elsevier B.V.

Interactions of atrazine with transition metal ions in aqueous media: experimental and computational approach.

PubMed

Kumar, Vijay; Kumar, Virender; Upadhyay, Niraj; Sharma, Sitansh

2015-10-01

Transition metal ions have their own significances and utility. Externally applied pesticides may alter the bioavailability of these metal ions to plants through the coordinating ability of these pesticides with metal ions. In current study a series of metal complexes containing atrazine (Atr) group(s) attached to metal(II) (M) frame, with the formula; [M(Atr) n .xH 2 O.yCl] (where M = Mn, Fe, Co, Ni, Cu or Zn; n = 1 or 2; x = 1-4; y = 1-2), have been synthesized for the first time to check the interactions of atrazine with transition metal ions. More importantly, all the complexes were synthesized at neutral pH in aqueous medium. The major differences among the FTIR spectra were observed between 3,700-2,800 and 1,800-1,350 cm -1 . On the basis of FTIR, CHN and computational study, it was observed that Mn, Ni and Cu formed complexes in 1:2 and Fe, Co and Zn in 1:1. The obtained results were supported by 3D molecular modeling using GAMESS computations as a package of ChemBio3D Ultra14 program. The FTIR spectral analysis and 3D molecular modeling suggests that the Atr can show coordination through the nitrogen (in between two side chains) of ring as well as nitrogen (non steric amine) of side chain with different metal ions.

Improving Semantic Updating Method on 3d City Models Using Hybrid Semantic-Geometric 3d Segmentation Technique

NASA Astrophysics Data System (ADS)

Sharkawi, K.-H.; Abdul-Rahman, A.

2013-09-01

Cities and urban areas entities such as building structures are becoming more complex as the modern human civilizations continue to evolve. The ability to plan and manage every territory especially the urban areas is very important to every government in the world. Planning and managing cities and urban areas based on printed maps and 2D data are getting insufficient and inefficient to cope with the complexity of the new developments in big cities. The emergence of 3D city models have boosted the efficiency in analysing and managing urban areas as the 3D data are proven to represent the real world object more accurately. It has since been adopted as the new trend in buildings and urban management and planning applications. Nowadays, many countries around the world have been generating virtual 3D representation of their major cities. The growing interest in improving the usability of 3D city models has resulted in the development of various tools for analysis based on the 3D city models. Today, 3D city models are generated for various purposes such as for tourism, location-based services, disaster management and urban planning. Meanwhile, modelling 3D objects are getting easier with the emergence of the user-friendly tools for 3D modelling available in the market. Generating 3D buildings with high accuracy also has become easier with the availability of airborne Lidar and terrestrial laser scanning equipments. The availability and accessibility to this technology makes it more sensible to analyse buildings in urban areas using 3D data as it accurately represent the real world objects. The Open Geospatial Consortium (OGC) has accepted CityGML specifications as one of the international standards for representing and exchanging spatial data, making it easier to visualize, store and manage 3D city models data efficiently. CityGML able to represents the semantics, geometry, topology and appearance of 3D city models in five well-defined Level-of-Details (LoD), namely LoD0 to LoD4. The accuracy and structural complexity of the 3D objects increases with the LoD level where LoD0 is the simplest LoD (2.5D; Digital Terrain Model (DTM) + building or roof print) while LoD4 is the most complex LoD (architectural details with interior structures). Semantic information is one of the main components in CityGML and 3D City Models, and provides important information for any analyses. However, more often than not, the semantic information is not available for the 3D city model due to the unstandardized modelling process. One of the examples is where a building is normally generated as one object (without specific feature layers such as Roof, Ground floor, Level 1, Level 2, Block A, Block B, etc). This research attempts to develop a method to improve the semantic data updating process by segmenting the 3D building into simpler parts which will make it easier for the users to select and update the semantic information. The methodology is implemented for 3D buildings in LoD2 where the buildings are generated without architectural details but with distinct roof structures. This paper also introduces hybrid semantic-geometric 3D segmentation method that deals with hierarchical segmentation of a 3D building based on its semantic value and surface characteristics, fitted by one of the predefined primitives. For future work, the segmentation method will be implemented as part of the change detection module that can detect any changes on the 3D buildings, store and retrieve semantic information of the changed structure, automatically updates the 3D models and visualize the results in a userfriendly graphical user interface (GUI).

Fast Geometric Consensus Approach for Protein Model Quality Assessment

PubMed Central

Adamczak, Rafal; Pillardy, Jaroslaw; Vallat, Brinda K.

2011-01-01

Abstract Model quality assessment (MQA) is an integral part of protein structure prediction methods that typically generate multiple candidate models. The challenge lies in ranking and selecting the best models using a variety of physical, knowledge-based, and geometric consensus (GC)-based scoring functions. In particular, 3D-Jury and related GC methods assume that well-predicted (sub-)structures are more likely to occur frequently in a population of candidate models, compared to incorrectly folded fragments. While this approach is very successful in the context of diversified sets of models, identifying similar substructures is computationally expensive since all pairs of models need to be superimposed using MaxSub or related heuristics for structure-to-structure alignment. Here, we consider a fast alternative, in which structural similarity is assessed using 1D profiles, e.g., consisting of relative solvent accessibilities and secondary structures of equivalent amino acid residues in the respective models. We show that the new approach, dubbed 1D-Jury, allows to implicitly compare and rank N models in O(N) time, as opposed to quadratic complexity of 3D-Jury and related clustering-based methods. In addition, 1D-Jury avoids computationally expensive 3D superposition of pairs of models. At the same time, structural similarity scores based on 1D profiles are shown to correlate strongly with those obtained using MaxSub. In terms of the ability to select the best models as top candidates 1D-Jury performs on par with other GC methods. Other potential applications of the new approach, including fast clustering of large numbers of intermediate structures generated by folding simulations, are discussed as well. PMID:21244273

Application of two- and three-dimensional computational fluid dynamics models to complex ecological stream flows

NASA Astrophysics Data System (ADS)

Shen, Yi; Diplas, Panayiotis

2008-01-01

SummaryComplex flow patterns generated by irregular channel topography, such as boulders, submerged large woody debris, riprap and spur dikes, provide unique habitat for many aquatic organisms. Numerical modeling of the flow structures surrounding these obstructions is challenging, yet it represents an important tool for aquatic habitat assessment. In this study, the ability of two- (2-D) and three-dimensional (3-D) computational fluid dynamics models to reproduce these localized complex flow features is examined. The 3-D model is validated with laboratory data obtained from the literature for the case of a flow around a hemisphere under emergent and submerged conditions. The performance of the 2-D and 3-D models is then evaluated by comparing the numerical results with field measurements of flow around several boulders located at a reach of the Smith River, a regulated mountainous stream, obtained at base and peak flows. Close agreement between measured values and the velocity profiles predicted by the two models is obtained outside the wakes behind the hemisphere and boulders. However, the results suggest that in the vicinity of these obstructions the 3-D model is better suited for reproducing the circulation flow behavior at both low and high discharges. Application of the 2-D and 3-D models to meso-scale stream flows of ecological significance is furthermore demonstrated by using a recently developed spatial hydraulic metric to quantify flow complexity surrounding a number of brown trout spawning sites. It is concluded that the 3-D model can provide a much more accurate description of the heterogeneous velocity patterns favored by many aquatic species over a broad range of flows, especially under deep flow conditions when the various obstructions are submerged. Issues pertaining to selection of appropriate models for a variety of flow regimes and potential implication of the 3-D model on the development of better habitat suitability criteria are discussed. The research suggests ways of improving the modeling practices for ecosystem management studies.

MP2, DFT-D, and PCM study of the HMB-TCNE complex: Thermodynamics, electric properties, and solvent effects

NASA Astrophysics Data System (ADS)

Kysel, Ondrej; Budzák, Scaronimon; Medveď, Miroslav; Mach, Pavel

Geometry, thermodynamic, and electric properties of the pi-EDA complex between hexamethylbenzene (HMB) and tetracyanoethylene (TCNE) are investigated at the MP2/6-31G* and, partly, DFT-D/6-31G* levels. Solvent effects on the properties are evaluated using the PCM model. Fully optimized HMB-TCNE geometry in gas phase is a stacking complex with an interplanar distance 2.87 × 10-10 m and the corresponding BSSE corrected interaction energy is -51.3 kJ mol-1. As expected, the interplanar distance is much shorter in comparison with HF and DFT results. However the crystal structures of both (HMB)2-TCNE and HMB-TCNE complexes have interplanar distances somewhat larger (3.18 and 3.28 × 10-10 m, respectively) than our MP2 gas phase value. Our estimate of the distance in CCl4 on the basis of PCM solvent effect study is also larger (3.06-3.16 × 10-10 m). The calculated enthalpy, entropy, Gibbs energy, and equilibrium constant of HMB-TCNE complex formation in gas phase are: DeltaH0 = -61.59 kJ mol-1, DeltaSc0 = -143 J mol-1 K-1, DeltaG0 = -18.97 kJ mol-1, and K = 2,100 dm3 mol-1. Experimental data, however, measured in CCl4 are significantly lower: DeltaH0 = -34 kJ mol-1, DeltaSc0 = -70.4 J mol-1 K-1, DeltaG0 = -13.01 kJ mol-1, and K = 190 dm3 mol-1. The differences are caused by solvation effects which stabilize more the isolated components than the complex. The total solvent destabilization of Gibbs energy of the complex relatively to that of components is equal to 5.9 kJ mol-1 which is very close to our PCM value 6.5 kJ mol-1. MP2/6-31G* dipole moment and polarizabilities are in reasonable agreement with experiment (3.56 D versus 2.8 D for dipole moment). The difference here is due to solvent effect which enlarges interplanar distance and thus decreases dipole moment value. The MP2/6-31G* study supplemented by DFT-D parameterization for enthalpy calculation, and by the PCM approach to include solvent effect seems to be proper tools to elucidate the properties of pi-EDA complexes.

Crystal structure of an antiviral ankyrin targeting the HIV-1 capsid and molecular modeling of the ankyrin-capsid complex.

PubMed

Praditwongwan, Warachai; Chuankhayan, Phimonphan; Saoin, Somphot; Wisitponchai, Tanchanok; Lee, Vannajan Sanghiran; Nangola, Sawitree; Hong, Saw See; Minard, Philippe; Boulanger, Pierre; Chen, Chun-Jung; Tayapiwatana, Chatchai

2014-08-01

Ankyrins are cellular repeat proteins, which can be genetically modified to randomize amino-acid residues located at defined positions in each repeat unit, and thus create a potential binding surface adaptable to macromolecular ligands. From a phage-display library of artificial ankyrins, we have isolated Ank(GAG)1D4, a trimodular ankyrin which binds to the HIV-1 capsid protein N-terminal domain (NTD(CA)) and has an antiviral effect at the late steps of the virus life cycle. In this study, the determinants of the Ank(GAG)1D4-NTD(CA) interaction were analyzed using peptide scanning in competition ELISA, capsid mutagenesis, ankyrin crystallography and molecular modeling. We determined the Ank(GAG)1D4 structure at 2.2 Å resolution, and used the crystal structure in molecular docking with a homology model of HIV-1 capsid. Our results indicated that NTD(CA) alpha-helices H1 and H7 could mediate the formation of the capsid-Ank(GAG)1D4 binary complex, but the interaction involving H7 was predicted to be more stable than with H1. Arginine-18 (R18) in H1, and R132 and R143 in H7 were found to be the key players of the Ank(GAG)1D4-NTD(CA) interaction. This was confirmed by R-to-A mutagenesis of NTD(CA), and by sequence analysis of trimodular ankyrins negative for capsid binding. In Ank(GAG)1D4, major interactors common to H1 and H7 were found to be S45, Y56, R89, K122 and K123. Collectively, our ankyrin-capsid binding analysis implied a significant degree of flexibility within the NTD(CA) domain of the HIV-1 capsid protein, and provided some clues for the design of new antivirals targeting the capsid protein and viral assembly.

Crystal structure of an antiviral ankyrin targeting the HIV-1 capsid and molecular modeling of the ankyrin-capsid complex

NASA Astrophysics Data System (ADS)

Praditwongwan, Warachai; Chuankhayan, Phimonphan; Saoin, Somphot; Wisitponchai, Tanchanok; Lee, Vannajan Sanghiran; Nangola, Sawitree; Hong, Saw See; Minard, Philippe; Boulanger, Pierre; Chen, Chun-Jung; Tayapiwatana, Chatchai

2014-08-01

Ankyrins are cellular repeat proteins, which can be genetically modified to randomize amino-acid residues located at defined positions in each repeat unit, and thus create a potential binding surface adaptable to macromolecular ligands. From a phage-display library of artificial ankyrins, we have isolated AnkGAG1D4, a trimodular ankyrin which binds to the HIV-1 capsid protein N-terminal domain (NTDCA) and has an antiviral effect at the late steps of the virus life cycle. In this study, the determinants of the AnkGAG1D4-NTDCA interaction were analyzed using peptide scanning in competition ELISA, capsid mutagenesis, ankyrin crystallography and molecular modeling. We determined the AnkGAG1D4 structure at 2.2 Å resolution, and used the crystal structure in molecular docking with a homology model of HIV-1 capsid. Our results indicated that NTDCA alpha-helices H1 and H7 could mediate the formation of the capsid-AnkGAG1D4 binary complex, but the interaction involving H7 was predicted to be more stable than with H1. Arginine-18 (R18) in H1, and R132 and R143 in H7 were found to be the key players of the AnkGAG1D4-NTDCA interaction. This was confirmed by R-to-A mutagenesis of NTDCA, and by sequence analysis of trimodular ankyrins negative for capsid binding. In AnkGAG1D4, major interactors common to H1 and H7 were found to be S45, Y56, R89, K122 and K123. Collectively, our ankyrin-capsid binding analysis implied a significant degree of flexibility within the NTDCA domain of the HIV-1 capsid protein, and provided some clues for the design of new antivirals targeting the capsid protein and viral assembly.

Evidence for a ternary complex formed between flavodoxin and cytochrome c3: 1H-NMR and molecular modeling studies.

PubMed

Palma, P N; Moura, I; LeGall, J; Van Beeumen, J; Wampler, J E; Moura, J J

1994-05-31

Small electron-transfer proteins such as flavodoxin (16 kDa) and the tetraheme cytochrome c3 (13 kDa) have been used to mimic, in vitro, part of the complex electron-transfer chain operating between substrate electron donors and respiratory electron acceptors, in sulfate-reducing bacteria (Desulfovibrio species). The nature and properties of the complex formed between these proteins are revealed by 1H-NMR and molecular modeling approaches. Our previous study with the Desulfovibrio vulgaris proteins [Moura, I., Moura, J.J. G., Santos, M.H., & Xavier, A. V. (1980) Cienc. Biol. (Portugal) 5, 195-197; Stewart, D.E. LeGall, J., Moura, I., Moura, J. J. G., Peck, H.D. Jr., Xavier, A. V., Weiner, P. K., & Wampler, J.E. (1988) Biochemistry 27, 2444-2450] indicated that the complex between cytochrome c3 and flavodoxin could be monitored by changes in the NMR signals of the heme methyl groups of the cytochrome and that the electrostatic surface charge (Coulomb's law) on the two proteins favored interaction between one unique heme of the cytochrome with flavodoxin. If the interaction is indeed driven by the electrostatic complementarity between the acidic flavodoxin and a unique positive region of the cytochrome c3, other homologous proteins from these two families of proteins might be expected to interact similarly. In this study, three homologous Desulfovibrio cytochromes c3 were used, which show a remarkable variation in their individual isoelectric points (ranging from 5.5 to 9.5). On the basis of data obtained from protein-protein titrations followed at specific proton NMR signals (i.e., heme methyl resonances), a binding model for this complex has been developed with evaluation of stoichiometry and binding constants. This binding model involves one site on the cytochromes c3 and two sites on the flavodoxin, with formation of a ternary complex at saturation. In order to understand the potential chemical form of the binding model, a structural model for the hypothetical ternary complex, formed between one molecule of Desulfovibrio salexigens flavodoxin and two molecules of cytochrome c3, is proposed. These molecular models of the complexes were constructed on the basis of complementarity of Coulombic electrostatic surface potentials, using the available X-ray structures of the isolated proteins and, when required, model structures (D. salexigens flavodoxin and Desulfovibrio desulfuricans ATCC 27774 cytochrome c3) predicted by homology modeling.

Modeling Biogeochemical Cycling of Heavy Metals in Lake Coeur d'Alene Sediments

NASA Astrophysics Data System (ADS)

Sengor, S. S.; Spycher, N.; Belding, E.; Curthoys, K.; Ginn, T. R.

2005-12-01

Mining of precious metals since the late 1800's have left Lake Coeur d'Alene (LCdA) sediments heavily enriched with toxic metals, including Cd, Cu, Pb, and Zn. Indigenous microbes however are capable of catalyzing reactions that detoxify the benthic and aqueous lake environments, and thus constitute an important driving component in the biogeochemical cycles of these metals. Here we report on the development of a quantitative model of transport, fate, exposure and effects of toxic compounds on benthic microbial communities at LCdA. First, chemical data from the LCdA area have been compiled from multiple sources to investigate trends in chemical occurrence, as well as to define model boundary conditions. The model is structured as 1-D diffusive reactive transport model to simulate spatial and temporal distribution of metals through the benthic sediments. Inorganic reaction processes included in the model are aqueous speciation, surface complexation, mineral precipitation/dissolution and abiotic redox reactions. Simulations with and without surface complexation are carried out to evaluate the effect of sorption and the conservative behaviour of metals within the benthic sediments under abiotic and purely diffusive transport. The 1-D inorganic diffusive transport model is then coupled to a biotic reaction network including consortium biodegradation kinetics with multiple electron acceptors, product toxicity, and energy partitioning. Multiyear simulations are performed, with water column chemistry established as a boundary condition from extant data, to explore the role of biogeochemical dynamics on benthic fluxes of metals in the long term.

A three-dimensional cell culture system as an in vitro canine mammary carcinoma model for the expression of connective tissue modulators.

PubMed

Cardoso, T C; Sakamoto, S S; Stockmann, D; Souza, T F B; Ferreira, H L; Gameiro, R; Vieira, F V; Louzada, M J Q; Andrade, A L; Flores, E F

2017-06-01

In this study, derived complex carcinoma (CC) and simple carcinoma (SC) cell lines were established and cultured under two-dimensional (2D) and three-dimensional (3D) conditions. The 3D was performed in six-well AlgiMatrix™ (LifeTechnologies®, Carlsbad, CA, USA) scaffolds, resulting in spheroids sized 50-125 µm for CC and 175-200 µm for SC. Cell viability was demonstrated up to 14 days for both models. Epidermal growth factor receptor (EGFR) was expressed in CC and SC in both systems. However, higher mRNA and protein levels were observed in SC 2D and 3D systems when compared with CC (P < 0.005). The connective tissue modulators, metalloproteinases-1, -2, -9 and -13 (MMPs), relaxin receptors 1 and 2 (RXR1 and RXR2) and E-cadherin (CDH1) were quantitated. All were upregulated similarly when canine mammary tumour (CMT)-derived cell lines were cultured under 3D AlgiMatrix, except CDH1 that was downregulated (P < 0.005). These results are promising towards the used of 3D system to increase a high throughput in vitro canine tumour model. © 2016 John Wiley & Sons Ltd.

Interactions of Kid–Kis toxin–antitoxin complexes with the parD operator-promoter region of plasmid R1 are piloted by the Kis antitoxin and tuned by the stoichiometry of Kid–Kis oligomers

PubMed Central

Monti, Maria C.; Hernández-Arriaga, Ana M.; Kamphuis, Monique B.; López-Villarejo, Juan; Heck, Albert J. R.; Boelens, Rolf; Díaz-Orejas, Ramón; van den Heuvel, Robert H. H.

2007-01-01

The parD operon of Escherichia coli plasmid R1 encodes a toxin–antitoxin system, which is involved in plasmid stabilization. The toxin Kid inhibits cell growth by RNA degradation and its action is neutralized by the formation of a tight complex with the antitoxin Kis. A fascinating but poorly understood aspect of the kid–kis system is its autoregulation at the transcriptional level. Using macromolecular (tandem) mass spectrometry and DNA binding assays, we here demonstrate that Kis pilots the interaction of the Kid–Kis complex in the parD regulatory region and that two discrete Kis-binding regions are present on parD. The data clearly show that only when the Kis concentration equals or exceeds the Kid concentration a strong cooperative effect exists between strong DNA binding and Kid2–Kis2–Kid2–Kis2 complex formation. We propose a model in which transcriptional repression of the parD operon is tuned by the relative molar ratio of the antitoxin and toxin proteins in solution. When the concentration of the toxin exceeds that of the antitoxin tight Kid2–Kis2–Kid2 complexes are formed, which only neutralize the lethal activity of Kid. Upon increasing the Kis concentration, (Kid2–Kis2)n complexes repress the kid–kis operon. PMID:17317682

Incorporating soil variability in continental soil water modelling: a trade-off between data availability and model complexity

NASA Astrophysics Data System (ADS)

Peeters, L.; Crosbie, R. S.; Doble, R.; van Dijk, A. I. J. M.

2012-04-01

Developing a continental land surface model implies finding a balance between the complexity in representing the system processes and the availability of reliable data to drive, parameterise and calibrate the model. While a high level of process understanding at plot or catchment scales may warrant a complex model, such data is not available at the continental scale. This data sparsity is especially an issue for the Australian Water Resources Assessment system, AWRA-L, a land-surface model designed to estimate the components of the water balance for the Australian continent. This study focuses on the conceptualization and parametrization of the soil drainage process in AWRA-L. Traditionally soil drainage is simulated with Richards' equation, which is highly non-linear. As general analytic solutions are not available, this equation is usually solved numerically. In AWRA-L however, we introduce a simpler function based on simulation experiments that solve Richards' equation. In the simplified function soil drainage rate, the ratio of drainage (D) over storage (S), decreases exponentially with relative water content. This function is controlled by three parameters, the soil water storage at field capacity (SFC), the drainage fraction at field capacity (KFC) and a drainage function exponent (β). [ ] D- -S- S = KF C exp - β (1 - SFC ) To obtain spatially variable estimates of these three parameters, the Atlas of Australian Soils is used, which lists soil hydraulic properties for each soil profile type. For each soil profile type in the Atlas, 10 days of draining an initially fully saturated, freely draining soil is simulated using HYDRUS-1D. With field capacity defined as the volume of water in the soil after 1 day, the remaining parameters can be obtained by fitting the AWRA-L soil drainage function to the HYDRUS-1D results. This model conceptualisation fully exploits the data available in the Atlas of Australian Soils, without the need to solve the non-linear Richards' equation for each time-step. The spatial distribution of long term recharge and baseflow obtained with a 30 year simulation of historic data using this parameterisation, corresponds well with the spatial patterns of groundwater recharge inferred from field measurements.

Theoretical study of inverted sandwich type complexes of 4d transition metal elements: interesting similarities to and differences from 3d transition metal complexes.

PubMed

Kurokawa, Yusaku I; Nakao, Yoshihide; Sakaki, Shigeyoshi

2012-03-08

Inverted sandwich type complexes (ISTCs) of 4d metals, (μ-η(6):η(6)-C(6)H(6))[M(DDP)](2) (DDPH = 2-{(2,6-diisopropylphenyl)amino}-4-{(2,6-diisopropylphenyl)imino}pent-2-ene; M = Y, Zr, Nb, Mo, and Tc), were investigated with density functional theory (DFT) and MRMP2 methods, where a model ligand AIP (AIPH = (Z)-1-amino-3-imino-prop-1-ene) was mainly employed. When going to Nb (group V) from Y (group III) in the periodic table, the spin multiplicity of the ground state increases in the order singlet, triplet, and quintet for M = Y, Zr, and Nb, respectively, like 3d ISTCs reported recently. This is interpreted with orbital diagram and number of d electrons. However, the spin multiplicity decreases to either singlet or triplet in ISTC of Mo (group VI) and to triplet in ISTC of Tc (group VII), where MRMP2 method is employed because the DFT method is not useful here. These spin multiplicities are much lower than the septet of ISTC of Cr and the nonet of that of Mn. When going from 3d to 4d, the position providing the maximum spin multiplicity shifts to group V from group VII. These differences arise from the size of the 4d orbital. Because of the larger size of the 4d orbital, the energy splitting between two d(δ) orbitals of M(AIP) and that between the d(δ) and d(π) orbitals are larger in the 4d complex than in the 3d complex. Thus, when occupation on the d(δ) orbital starts, the low spin state becomes ground state, which occurs at group VI. Hence, the ISTC of Nb (group V) exhibits the maximum spin multiplicity.

Probing 1D superlattices at the LaAlO3 / SrTiO3 interface

NASA Astrophysics Data System (ADS)

Briggeman, M.; Huang, M.; Tylan-Tyler, A.; Irvin, P.; Levy, J.; Lee, J.-W.; Lee, H.; Eom, C.-B.

Complex oxides and other quantum systems exhibit behavior that is currently too complex to be understood using analytic or computational methods. One approach is to use a configurable quantum system whose Hamiltonian can be mapped onto the system of interest. This approach, known as quantum simulation, requires a rich physical system whose quanta and interactions can be controlled precisely, at the level of single electrons and other degrees of freedom. Here we describe steps toward developing a quantum simulation platform, using the complex oxide heterostructure LaAlO3 / SrTiO3 , by creating quantum systems with features comparable to the mean spacing between electrons. This interface has strong, sign changing, gate-tunable electron-electron interactions that can strongly influence the quantum ground state. We explore the magnetotransport properties of 1D superlattices, where periodic modulation produces reproducible dispersive features not seen in control structures. The results of these experiments can be compared with effective 1D model Hamiltonians to bridge experiment and theory and enable quantum simulation of more complex systems. We gratefully acknowledge financial support from AFOSR (FA9550-12-1- 0057 (JL) and FA9550-12-1-0342 (CBE)), ONR N00014-15-1-2847 (JL), and NSF DMR-1234096 (CBE).

Integrative Approach for Computationally Inferring Interactions between the Alpha and Beta Subunits of the Calcium-Activated Potassium Channel (BK): a Docking Study

PubMed Central

González, Janneth; Gálvez, Angela; Morales, Ludis; Barreto, George E.; Capani, Francisco; Sierra, Omar; Torres, Yolima

2013-01-01

Three-dimensional models of the alpha- and beta-1 subunits of the calcium-activated potassium channel (BK) were predicted by threading modeling. A recursive approach comprising of sequence alignment and model building based on three templates was used to build these models, with the refinement of non-conserved regions carried out using threading techniques. The complex formed by the subunits was studied by means of docking techniques, using 3D models of the two subunits, and an approach based on rigid-body structures. Structural effects of the complex were analyzed with respect to hydrogen-bond interactions and binding-energy calculations. Potential interaction sites of the complex were determined by referencing a study of the difference accessible surface area (DASA) of the protein subunits in the complex. PMID:23492851

Optical Coherence Tomography Noise Reduction Using Anisotropic Local Bivariate Gaussian Mixture Prior in 3D Complex Wavelet Domain

PubMed Central

Sonka, Milan; Abramoff, Michael D.

2013-01-01

In this paper, MMSE estimator is employed for noise-free 3D OCT data recovery in 3D complex wavelet domain. Since the proposed distribution for noise-free data plays a key role in the performance of MMSE estimator, a priori distribution for the pdf of noise-free 3D complex wavelet coefficients is proposed which is able to model the main statistical properties of wavelets. We model the coefficients with a mixture of two bivariate Gaussian pdfs with local parameters which are able to capture the heavy-tailed property and inter- and intrascale dependencies of coefficients. In addition, based on the special structure of OCT images, we use an anisotropic windowing procedure for local parameters estimation that results in visual quality improvement. On this base, several OCT despeckling algorithms are obtained based on using Gaussian/two-sided Rayleigh noise distribution and homomorphic/nonhomomorphic model. In order to evaluate the performance of the proposed algorithm, we use 156 selected ROIs from 650 × 512 × 128 OCT dataset in the presence of wet AMD pathology. Our simulations show that the best MMSE estimator using local bivariate mixture prior is for the nonhomomorphic model in the presence of Gaussian noise which results in an improvement of 7.8 ± 1.7 in CNR. PMID:24222760

A 3D puzzle approach to building protein-DNA structures.

PubMed

Hinton, Deborah M

2017-03-15

Despite recent advances in structural analysis, it is still challenging to obtain a high-resolution structure for a complex of RNA polymerase, transcriptional factors, and DNA. However, using biochemical constraints, 3D printed models of available structures, and computer modeling, one can build biologically relevant models of such supramolecular complexes.

The dopamine D2 receptor dimer and its interaction with homobivalent antagonists: homology modeling, docking and molecular dynamics.

PubMed

Kaczor, Agnieszka A; Jörg, Manuela; Capuano, Ben

2016-09-01

In order to apply structure-based drug design techniques to G protein-coupled receptor complexes, it is essential to model their 3D structure and to identify regions that are suitable for selective drug binding. For this purpose, we have developed and tested a multi-component protocol to model the inactive conformation of the dopamine D2 receptor dimer, suitable for interaction with homobivalent antagonists. Our approach was based on protein-protein docking, applying the Rosetta software to obtain populations of dimers as present in membranes with all the main possible interfaces. Consensus scoring based on the values and frequencies of best interfaces regarding four scoring parameters, Rosetta interface score, interface area, free energy of binding and energy of hydrogen bond interactions indicated that the best scored dimer model possesses a TM4-TM5-TM7-TM1 interface, which is in agreement with experimental data. This model was used to study interactions of the previously published dopamine D2 receptor homobivalent antagonists based on clozapine,1,4-disubstituted aromatic piperidines/piperazines and arylamidoalkyl substituted phenylpiperazine pharmacophores. It was found that the homobivalent antagonists stabilize the receptor-inactive conformation by maintaining the ionic lock interaction, and change the dimer interface by disrupting a set of hydrogen bonds and maintaining water- and ligand-mediated hydrogen bonds in the extracellular and intracellular part of the interface. Graphical Abstract Structure of the final model of the dopamine D2 receptor homodimer, indicating the distancebetween Tyr37 and Tyr 5.42 in the apo form (left) and in the complex with the ligand (right).

Efficient Analysis of Complex Structures

NASA Technical Reports Server (NTRS)

Kapania, Rakesh K.

2000-01-01

Last various accomplishments achieved during this project are : (1) A Survey of Neural Network (NN) applications using MATLAB NN Toolbox on structural engineering especially on equivalent continuum models (Appendix A). (2) Application of NN and GAs to simulate and synthesize substructures: 1-D and 2-D beam problems (Appendix B). (3) Development of an equivalent plate-model analysis method (EPA) for static and vibration analysis of general trapezoidal built-up wing structures composed of skins, spars and ribs. Calculation of all sorts of test cases and comparison with measurements or FEA results. (Appendix C). (4) Basic work on using second order sensitivities on simulating wing modal response, discussion of sensitivity evaluation approaches, and some results (Appendix D). (5) Establishing a general methodology of simulating the modal responses by direct application of NN and by sensitivity techniques, in a design space composed of a number of design points. Comparison is made through examples using these two methods (Appendix E). (6) Establishing a general methodology of efficient analysis of complex wing structures by indirect application of NN: the NN-aided Equivalent Plate Analysis. Training of the Neural Networks for this purpose in several cases of design spaces, which can be applicable for actual design of complex wings (Appendix F).

The Implications of 3D Thermal Structure on 1D Atmospheric Retrieval

NASA Astrophysics Data System (ADS)

Blecic, Jasmina; Dobbs-Dixon, Ian; Greene, Thomas

2017-10-01

Using the atmospheric structure from a 3D global radiation-hydrodynamic simulation of HD 189733b and the open-source Bayesian Atmospheric Radiative Transfer (BART) code, we investigate the difference between the secondary-eclipse temperature structure produced with a 3D simulation and the best-fit 1D retrieved model. Synthetic data are generated by integrating the 3D models over the Spitzer, the Hubble Space Telescope (HST), and the James Web Space Telescope (JWST) bandpasses, covering the wavelength range between 1 and 11 μm where most spectroscopically active species have pronounced features. Using the data from different observing instruments, we present detailed comparisons between the temperature-pressure profiles recovered by BART and those from the 3D simulations. We calculate several averages of the 3D thermal structure and explore which particular thermal profile matches the retrieved temperature structure. We implement two temperature parameterizations that are commonly used in retrieval to investigate different thermal profile shapes. To assess which part of the thermal structure is best constrained by the data, we generate contribution functions for our theoretical model and each of our retrieved models. Our conclusions are strongly affected by the spectral resolution of the instruments included, their wavelength coverage, and the number of data points combined. We also see some limitations in each of the temperature parametrizations, as they are not able to fully match the complex curvatures that are usually produced in hydrodynamic simulations. The results show that our 1D retrieval is recovering a temperature and pressure profile that most closely matches the arithmetic average of the 3D thermal structure. When we use a higher resolution, more data points, and a parametrized temperature profile that allows more flexibility in the middle part of the atmosphere, we find a better match between the retrieved temperature and pressure profile and the arithmetic average. The Spitzer and HST simulated observations sample deep parts of the planetary atmosphere and provide fewer constraints on the temperature and pressure profile, while the JWST observations sample the middle part of the atmosphere, providing a good match with the middle and most complex part of the arithmetic average of the 3D temperature structure.

Cooperation of p27Kip1 and p18INK4c in Progestin-Mediated Cell Cycle Arrest in T-47D Breast Cancer Cells

PubMed Central

Swarbrick, Alexander; Lee, Christine S. L.; Sutherland, Robert L.; Musgrove, Elizabeth A.

2000-01-01

The steroid hormone progesterone regulates proliferation and differentiation in the mammary gland and uterus by cell cycle phase-specific actions. The long-term effect of progestins on T-47D breast cancer cells is inhibition of cellular proliferation. This is accompanied by decreased G1 cyclin-dependent kinase (CDK) activities, redistribution of the CDK inhibitor p27Kip1 among these CDK complexes, and alterations in the elution profile of cyclin E-Cdk2 upon gel filtration chromatography, such that high-molecular-weight complexes predominate. This study aimed to determine the relative contribution of CDK inhibitors to these events. Following progestin treatment, the majority of cyclin E- and D-CDK complexes were bound to p27Kip1 and few were bound to p21Cip1. In vitro, recombinant His6-p27 could quantitatively reproduce the effects on cyclin E-Cdk2 kinase activity and the shift in molecular weight observed following progestin treatment. In contrast, cyclin D-Cdk4 was not inhibited by His6-p27 in vitro or p27Kip1 in vivo. However, an increase in the expression of the Cdk4/6 inhibitor p18INK4c and its extensive association with Cdk4 and Cdk6 were apparent following progestin treatment. Recombinant p18INK4c led to the reassortment of cyclin-CDK-CDK inhibitor complexes in vitro, with consequent decrease in cyclin E-Cdk2 activity. These results suggest a concerted model of progestin action whereby p27Kip1 and p18INK4c cooperate to inhibit cyclin E-Cdk2 and Cdk4. Since similar models have been developed for growth inhibition by transforming growth factor β and during adipogenesis, interaction between the Cip/Kip and INK4 families of inhibitors may be a common theme in physiological growth arrest and differentiation. PMID:10713180

Semiempirical Quantum Chemistry Model for the Lanthanides: RM1 (Recife Model 1) Parameters for Dysprosium, Holmium and Erbium

PubMed Central

Filho, Manoel A. M.; Dutra, José Diogo L.; Rocha, Gerd B.; Simas, Alfredo M.; Freire, Ricardo O.

2014-01-01

Complexes of dysprosium, holmium, and erbium find many applications as single-molecule magnets, as contrast agents for magnetic resonance imaging, as anti-cancer agents, in optical telecommunications, etc. Therefore, the development of tools that can be proven helpful to complex design is presently an active area of research. In this article, we advance a major improvement to the semiempirical description of lanthanide complexes: the Recife Model 1, RM1, model for the lanthanides, parameterized for the trications of Dy, Ho, and Er. By representing such lanthanide in the RM1 calculation as a three-electron atom with a set of 5 d, 6 s, and 6 p semiempirical orbitals, the accuracy of the previous sparkle models, mainly concentrated on lanthanide-oxygen and lanthanide-nitrogen distances, is extended to other types of bonds in the trication complexes’ coordination polyhedra, such as lanthanide-carbon, lanthanide-chlorine, etc. This is even more important as, for example, lanthanide-carbon atom distances in the coordination polyhedra of the complexes comprise about 30% of all distances for all complexes of Dy, Ho, and Er considered. Our results indicate that the average unsigned mean error for the lanthanide-carbon distances dropped from an average of 0.30 Å, for the sparkle models, to 0.04 Å for the RM1 model for the lanthanides; for a total of 509 such distances for the set of all Dy, Ho, and Er complexes considered. A similar behavior took place for the other distances as well, such as lanthanide-chlorine, lanthanide-bromine, lanthanide, phosphorus and lanthanide-sulfur. Thus, the RM1 model for the lanthanides, being advanced in this article, broadens the range of application of semiempirical models to lanthanide complexes by including comprehensively many other types of bonds not adequately described by the previous models. PMID:24497945

The Electronic Structure of Mn in Oxides, Coordination Complexes, and the Oxygen-Evolving Complex of Photosystem II Studied by Resonant Inelastic X-ray Scattering

PubMed Central

Yano, Junko; Visser, Hendrik; Robblee, John H.; Gu, Weiwei; de Groot, Frank M. F.; Christou, George; Pecoraro, Vincent L.

2014-01-01

Resonant inelastic X-ray scattering (RIXS) was used to collect Mn K pre-edge spectra and to study the electronic structure in oxides, molecular coordination complexes, as well as the S1 and S2 states of the oxygen-evolving complex (OEC) of photosystem II (PS II). The RIXS data yield two-dimensional plots that can be interpreted along the incident (absorption) energy or the energy transfer axis. The second energy dimension separates the pre-edge (predominantly 1s to 3d transitions) from the main K-edge, and a detailed analysis is thus possible. The 1s2p RIXS final-state electron configuration along the energy transfer axis is identical to conventional L-edge absorption spectroscopy, and the RIXS spectra are therefore sensitive to the Mn spin state. This new technique thus yields information on the electronic structure that is not accessible in conventional K-edge absorption spectroscopy. The line splittings can be understood within a ligand field multiplet model, i.e., (3d,3d) and (2p,3d) two-electron interactions are crucial to describe the spectral shapes in all systems. We propose to explain the shift of the K pre-edge absorption energy upon Mn oxidation in terms of the effective number of 3d electrons (fractional 3d orbital population). The spectral changes in the Mn 1s2p3/2 RIXS spectra between the PS II S1 and S2 states are small compared to that of the oxides and two of the coordination complexes (MnIII(acac)3 and MnIV(sal)2(bipy)). We conclude that the electron in the step from S1 to S2 is transferred from a strongly delocalized orbital. PMID:15303869

Assembly and property research on seven 0D-3D complexes derived from imidazole dicarboxylate and 1,2-bi(pyridin-4-yl)ethene

NASA Astrophysics Data System (ADS)

Mu, Bao; Li, Qian; Lv, Lei; Yang, Dan-Dan; Wang, Qing; Huang, Ru-Dan

2015-03-01

The hydrothermal reaction of transition metals, 1H-imidazole-4,5-dicarboxylic acid (H3ImDC) and 1,2-bi(pyridin-4-yl)ethene (bpe) affords a series of new complexes, namely, [Mn(HImDC)(bpe)(H2O)] (1), [M(H2ImDC)2(H2O)2]·(bpe) (M=Fe(2), Co(3), Zn(4), Cd(6)), [Zn3(ImDC)2(bpe)(H2O)]·3H2O (5) and [Cd(H2ImDC)(bpe)] (7), which are characterized by elemental analyses, IR, TG, XRPD and single crystal X-ray diffraction. Complex 1 exhibits a one dimensional (1D) zigzag chain with two types of irregular rings, and the 1D chains are linked to form a three dimensional (3D) supramolecular framework by the hydrogen bonding interactions (O-H•••O and O-H•••N). Complexes 2-4 and 6 are isomorphous, and they display the mononuclear structures. In these complexes, the O-H•••O and O-H•••N hydrogen bonds play an important role in sustaining the whole 3D supramolecular frameworks. Complex 5 shows a (3,3)-connected 3D framework with (103) topology, and the lattice water molecules as guest molecules exist in the 3D framework. Complex 7 is a wave-like two dimensional (2D) structure, in which the adjacent 1D chains point at the opposite directions. Moreover, the fluorescent properties of complexes 1-7 and the magnetic property of 1 have been investigated. The water vapor adsorption for complex 5 has been researched at 298 K.

Insulin-sensitizing and cholesterol-lowering effects of chromium (D-Phenylalanine)3.

PubMed

Yang, Xiaoping; Li, Shi-Yan; Dong, Feng; Ren, Jun; Sreejayan, Nair

2006-07-01

Low-molecular weight organic chromium complexes are thought to play a key role in carbohydrate and lipid metabolism and therefore have been gaining popularity as nutritional supplement for patients with diabetes and concomitant lipid disorders. The aim of the present study was to evaluate the effects of a novel synthetic chromium (d-phenylalanine)(3) complex on insulin-sensitivity, plasma lipid-profile and oxidant stress in a mouse model of type II diabetes. Plasma glucose levels following intraperitoneal insulin-challenge (1U/kg) to obese ob/ob(+/+) mice treated with Cr(d-Phe)(3) (150 microg/kg/day for 6 weeks) were significantly lower compared to vehicle-control (control: 175.8+/-43.2mg/dL versus Cr(d-Phe)(3) 115.3+/-18.0mg/dL, p<0.01, n=12). Total serum cholesterol to high-density lipoprotein ratio was significantly reduced following Cr(d-Phe)(3)-treatment (control: 2.19+/-0.08 versus Cr(d-Phe)(3) 1.63+/-0.05; p<0.05). Hepatic oxidant stress, assessed as malondialdehyde equivalents and protein-carbonyl content were significantly attenuated following Cr(d-Phe)(3) treatment. The complex also inhibited lipid-peroxidation in vitro, in a concentration dependent manner. Taken together, these data suggest that Cr(d-Phe)(3) may be of potential value in the therapy or prophylaxis of insulin-resistance and dyslipidemia associated with obesity.

Ingasaponin, a complex triterpenoid saponin with immunological adjuvant activity from Inga laurina.

PubMed

Cruz, Maria de Fátima Simão Jucá; Pereira, Gabriela Moysés; Ribeiro, Marcela Gonçalves; da Silva, Ari Miranda; Tinoco, Luzineide Wanderley; da Silva, Bernadete Pereira; Parente, José Paz

2016-02-01

As part of our search of bioactive saponins from Brazilian plants, phytochemical study of the seeds of Inga laurina led to the isolation of a new complex triterpenoid saponin, named ingasaponin. It is the first saponin isolated from a species of Inga genus. It was isolated by using chromatographic methods and its structural elucidation was performed using detailed analyses of (1)H and (13)C NMR spectra including 2D-NMR spectroscopic techniques and chemical conversions. Its structure was established as 21-[[(2E,6S)-6-[[6-deoxy-4-O-[(2E,6S)-6-[(β-D-glucopyranosyl)oxy]-2,6-dimethyl-1-oxo-2,7-octadienyl]-[(β-D-glucopyranosyl)oxy]-2,6-dimethyl-1-oxo-2,7-octadienyl]-[(β-D-glucopyranosyl)oxy]-2,6-dimethyl-1-oxo-2,7-octadienyl]-[(β-D-glucopyranosyl)oxy]-2-(hydroxymethyl)-6-methyl-1-oxo-2,7-octadienyl]oxy]-16-hydroxy-3-[[O-β-D-xylopyranosyl-(1 → 2)-O-α-L-arabinopyranosyl-(1 → 6)-2-(acetylamino)-2-deoxy-β-D-glucopyranosyl]oxy]-(3β,16α,21β)-olean-12-en-28-oic acid O-α-L-arabinofuranosyl-(1 → 4)-O-[β-D-glucopyranosyl-(1 → 3)]-O-6-deoxy-α-L-mannopyranosyl-(1 → 2)-β-D-glucopyranosyl ester (1). The hemolytic potential of 1 was evaluated using in vitro assays, and its adjuvant activity on the cellular immune response against ovalbumin antigen was investigated using in vivo models. Copyright © 2015 Elsevier Ltd. All rights reserved.

Utility of a super-flexible three-dimensional printed heart model in congenital heart surgery.

PubMed

Hoashi, Takaya; Ichikawa, Hajime; Nakata, Tomohiro; Shimada, Masatoshi; Ozawa, Hideto; Higashida, Akihiko; Kurosaki, Kenichi; Kanzaki, Suzu; Shiraishi, Isao

2018-05-28

The objective of this study was to assess the utility of 3D printed heart models of congenital heart disease for preoperative surgical simulation. Twenty patient-specific 3D models were created between March 2015 and August 2017. All operations were performed by a young consultant surgeon who had no prior experience with complex biventricular repair. All 15 patients with balanced ventricles had outflow tract malformations (double-outlet right ventricle in 7 patients, congenitally corrected transposition of great arteries in 5, transposition of great arteries in 1, interrupted aortic arch Type B in 1, tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries in 1). One patient had hypoplastic left heart complex, and the remaining 4 patients had a functional single ventricle. The median age at operation was 1.4 (range 0.1-5.9) years. Based on a multislice computed tomography data set, the 3D models were made of polyurethane resins using stereolithography as the printing technology and vacuum casting as the manufacturing method. All but 4 patients with a functional single ventricle underwent complete biventricular repair. The median cardiopulmonary bypass time and aortic cross-clamp time were 345 (110-570) min and 114 (35-293) min, respectively. During the median follow-up period of 1.3 (0.1-2.5) years, no mortality was observed. None of the patients experienced surgical heart block or systemic ventricular outflow tract obstruction. Three-dimensional printed heart models showed potential utility, especially in understanding the relationship between intraventricular communications and great vessels, as well as in simulation for creating intracardiac pathways.

Multidimensional Multiphysics Simulation of TRISO Particle Fuel

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

J. D. Hales; R. L. Williamson; S. R. Novascone

2013-11-01

Multidimensional multiphysics analysis of TRISO-coated particle fuel using the BISON finite-element based nuclear fuels code is described. The governing equations and material models applicable to particle fuel and implemented in BISON are outlined. Code verification based on a recent IAEA benchmarking exercise is described, and excellant comparisons are reported. Multiple TRISO-coated particles of increasing geometric complexity are considered. It is shown that the code's ability to perform large-scale parallel computations permits application to complex 3D phenomena while very efficient solutions for either 1D spherically symmetric or 2D axisymmetric geometries are straightforward. Additionally, the flexibility to easily include new physical andmore » material models and uncomplicated ability to couple to lower length scale simulations makes BISON a powerful tool for simulation of coated-particle fuel. Future code development activities and potential applications are identified.« less

Rate-distortion analysis of dead-zone plus uniform threshold scalar quantization and its application--part II: two-pass VBR coding for H.264/AVC.

PubMed

Sun, Jun; Duan, Yizhou; Li, Jiangtao; Liu, Jiaying; Guo, Zongming

2013-01-01

In the first part of this paper, we derive a source model describing the relationship between the rate, distortion, and quantization steps of the dead-zone plus uniform threshold scalar quantizers with nearly uniform reconstruction quantizers for generalized Gaussian distribution. This source model consists of rate-quantization, distortion-quantization (D-Q), and distortion-rate (D-R) models. In this part, we first rigorously confirm the accuracy of the proposed source model by comparing the calculated results with the coding data of JM 16.0. Efficient parameter estimation strategies are then developed to better employ this source model in our two-pass rate control method for H.264 variable bit rate coding. Based on our D-Q and D-R models, the proposed method is of high stability, low complexity and is easy to implement. Extensive experiments demonstrate that the proposed method achieves: 1) average peak signal-to-noise ratio variance of only 0.0658 dB, compared to 1.8758 dB of JM 16.0's method, with an average rate control error of 1.95% and 2) significant improvement in smoothing the video quality compared with the latest two-pass rate control method.

Distinct conformations of the protein complex p97-Ufd1-Npl4 revealed by electron cryomicroscopy

PubMed Central

Bebeacua, Cecilia; Förster, Andreas; McKeown, Ciarán; Meyer, Hemmo H.; Zhang, Xiaodong; Freemont, Paul S.

2012-01-01

p97 is a key regulator of numerous cellular pathways and associates with ubiquitin-binding adaptors to remodel ubiquitin-modified substrate proteins. How adaptor binding to p97 is coordinated and how adaptors contribute to substrate remodeling is unclear. Here we present the 3D electron cryomicroscopy reconstructions of the major Ufd1-Npl4 adaptor in complex with p97. Our reconstructions show that p97-Ufd1-Npl4 is highly dynamic and that Ufd1-Npl4 assumes distinct positions relative to the p97 ring upon addition of nucleotide. Our results suggest a model for substrate remodeling by p97 and also explains how p97-Ufd1-Npl4 could form other complexes in a hierarchical model of p97-cofactor assembly. PMID:22232657

Modeling biophysical properties of broad-leaved stands in the hyrcanian forests of Iran using fused airborne laser scanner data and ultraCam-D images

NASA Astrophysics Data System (ADS)

Mohammadi, Jahangir; Shataee, Shaban; Namiranian, Manochehr; Næsset, Erik

2017-09-01

Inventories of mixed broad-leaved forests of Iran mainly rely on terrestrial measurements. Due to rapid changes and disturbances and great complexity of the silvicultural systems of these multilayer forests, frequent repetition of conventional ground-based plot surveys is often cost prohibitive. Airborne laser scanning (ALS) and multispectral data offer an alternative or supplement to conventional inventories in the Hyrcanian forests of Iran. In this study, the capability of a combination of ALS and UltraCam-D data to model stand volume, tree density, and basal area using random forest (RF) algorithm was evaluated. Systematic sampling was applied to collect field plot data on a 150 m × 200 m sampling grid within a 1100 ha study area located at 36°38‧- 36°42‧N and 54°24‧-54°25‧E. A total of 308 circular plots (0.1 ha) were measured for calculation of stand volume, tree density, and basal area per hectare. For each plot, a set of variables was extracted from both ALS and multispectral data. The RF algorithm was used for modeling of the biophysical properties using ALS and UltraCam-D data separately and combined. The results showed that combining the ALS data and UltraCam-D images provided a slight increase in prediction accuracy compared to separate modeling. The RMSE as percentage of the mean, the mean difference between observed and predicted values, and standard deviation of the differences using a combination of ALS data and UltraCam-D images in an independent validation at 0.1-ha plot level were 31.7%, 1.1%, and 84 m3 ha-1 for stand volume; 27.2%, 0.86%, and 6.5 m2 ha-1 for basal area, and 35.8%, -4.6%, and 77.9 n ha-1 for tree density, respectively. Based on the results, we conclude that fusion of ALS and UltraCam-D data may be useful for modeling of stand volume, basal area, and tree density and thus gain insights into structural characteristics in the complex Hyrcanian forests.

Ternary copper(II) complex: NCI60 screening, toxicity studies, and evaluation of efficacy in xenograft models of nasopharyngeal carcinoma.

PubMed

Ahmad, Munirah; Suhaimi, Shazlan-Noor; Chu, Tai-Lin; Abdul Aziz, Norazlin; Mohd Kornain, Noor-Kaslina; Samiulla, D S; Lo, Kwok-Wai; Ng, Chew-Hee; Khoo, Alan Soo-Beng

2018-01-01

Copper(II) ternary complex, [Cu(phen)(C-dmg)(H2O)]NO3 was evaluated against a panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II) complex displayed broad spectrum cytotoxicity against multiple cancer types, including lung, colon, central nervous system, melanoma, ovarian, and prostate cancer cell lines in the NCI-60 panel. The Cu(II) complex did not cause significant induction of cytochrome P450 (CYP) 3A and 1A enzymes but moderately inhibited CYP isoforms 1A2, 2C9, 2C19, 2D6, 2B6, 2C8 and 3A4. The complex significantly inhibited tumor growth in nasopharyngeal carcinoma xenograft bearing mice models at doses which were well tolerated without causing significant or permanent toxic side effects. However, higher doses which resulted in better inhibition of tumor growth also resulted in toxicity.

Extension of RCC Topological Relations for 3d Complex Objects Components Extracted from 3d LIDAR Point Clouds

NASA Astrophysics Data System (ADS)

Xing, Xu-Feng; Abolfazl Mostafavia, Mir; Wang, Chen

2016-06-01

Topological relations are fundamental for qualitative description, querying and analysis of a 3D scene. Although topological relations for 2D objects have been extensively studied and implemented in GIS applications, their direct extension to 3D is very challenging and they cannot be directly applied to represent relations between components of complex 3D objects represented by 3D B-Rep models in R3. Herein we present an extended Region Connection Calculus (RCC) model to express and formalize topological relations between planar regions for creating 3D model represented by Boundary Representation model in R3. We proposed a new dimension extended 9-Intersection model to represent the basic relations among components of a complex object, including disjoint, meet and intersect. The last element in 3*3 matrix records the details of connection through the common parts of two regions and the intersecting line of two planes. Additionally, this model can deal with the case of planar regions with holes. Finally, the geometric information is transformed into a list of strings consisting of topological relations between two planar regions and detailed connection information. The experiments show that the proposed approach helps to identify topological relations of planar segments of point cloud automatically.

An evaluation of 3-D traffic simulation modeling capabilities

DOT National Transportation Integrated Search

2007-06-01

The use of 3D modeling in simulation has become the standard for both the military and private sector. Compared to physical models, 3D models are more affordable, more flexible, and can incorporate complex operations. Unlike a physical model, a dynam...

Bim Automation: Advanced Modeling Generative Process for Complex Structures

NASA Astrophysics Data System (ADS)

Banfi, F.; Fai, S.; Brumana, R.

2017-08-01

The new paradigm of the complexity of modern and historic structures, which are characterised by complex forms, morphological and typological variables, is one of the greatest challenges for building information modelling (BIM). Generation of complex parametric models needs new scientific knowledge concerning new digital technologies. These elements are helpful to store a vast quantity of information during the life cycle of buildings (LCB). The latest developments of parametric applications do not provide advanced tools, resulting in time-consuming work for the generation of models. This paper presents a method capable of processing and creating complex parametric Building Information Models (BIM) with Non-Uniform to NURBS) with multiple levels of details (Mixed and ReverseLoD) based on accurate 3D photogrammetric and laser scanning surveys. Complex 3D elements are converted into parametric BIM software and finite element applications (BIM to FEA) using specific exchange formats and new modelling tools. The proposed approach has been applied to different case studies: the BIM of modern structure for the courtyard of West Block on Parliament Hill in Ottawa (Ontario) and the BIM of Masegra Castel in Sondrio (Italy), encouraging the dissemination and interaction of scientific results without losing information during the generative process.

Efficient two-dimensional compressive sensing in MIMO radar

NASA Astrophysics Data System (ADS)

Shahbazi, Nafiseh; Abbasfar, Aliazam; Jabbarian-Jahromi, Mohammad

2017-12-01

Compressive sensing (CS) has been a way to lower sampling rate leading to data reduction for processing in multiple-input multiple-output (MIMO) radar systems. In this paper, we further reduce the computational complexity of a pulse-Doppler collocated MIMO radar by introducing a two-dimensional (2D) compressive sensing. To do so, we first introduce a new 2D formulation for the compressed received signals and then we propose a new measurement matrix design for our 2D compressive sensing model that is based on minimizing the coherence of sensing matrix using gradient descent algorithm. The simulation results show that our proposed 2D measurement matrix design using gradient decent algorithm (2D-MMDGD) has much lower computational complexity compared to one-dimensional (1D) methods while having better performance in comparison with conventional methods such as Gaussian random measurement matrix.

Synthesis, structure, photoluminescence and antitumour activity of zinc complex based on 2-(2-(1H-benzo-[d]imidazol-2-yl)benzyl)-1H-benzo-[d]imidazole

NASA Astrophysics Data System (ADS)

Che, Zhijian; Wang, Shaoxiang; Liu, Shenggui; Li, Guobi; Wu, Qiting; Lin, Chunyu; Kong, Linglang; Wang, Sheng

2015-01-01

A new complex [Zn(bbb)Cl2]·DMF, where bbb is 2-(2-(1H-benzo[d]imidazol-2-yl)benzyl)-1H-benzo[d]imidazole, was synthesized and characterized by element analysis, 1H NMR and X-ray single crystal structure analyses. For complex: crystal system, triclinic, space group, P-1, a = 9.4661(13), b = 10.3534(14), c = 13.0025(18) Å, α = 73.477(2), β = 80.743(2), γ = 88.658(2)°, V = 1205.5(3) Å3, Z = 2. In this complex, the Zn2+ distorted tetrahedron geometry is coordinated by two nitrogen atoms from 2-(2-(1H-benzo[d]imidazol-2-yl)benzyl)-1H-benzo[d]imidazole and two Cl-. The complex emits yellow green luminescence with the maximal emission peak at 550 nm in DMF solution. The complex exhibits inhibition on the growth of Eca109 cancer cell with IC50 value of 8.9 ± 1.1 μM, which was lower than that of cisplatin (14.3 ± 1.4 μM). This complex has potential application in treatment of esophageal cancer.

Ground Motion Modeling in the Eastern Caucasus

DOE PAGES

Pitarka, Arben; Gok, Rengin; Yetirmishli, Gurban; ...

2016-05-13

In this paper, we analyzed the performance of a preliminary three-dimensional (3D) velocity model of the Eastern Caucasus covering most of the Azerbaijan. The model was developed in support to long-period ground motion simulations and seismic hazard assessment from regional earthquakes in Azerbaijan. The model’s performance was investigated by simulating ground motion from the damaging Mw 5.9, 2012 Zaqatala earthquake, which was well recorded throughout the region by broadband seismic instruments. In our simulations, we use a parallelized finite-difference method of fourth-order accuracy. The comparison between the simulated and recorded ground motion velocity in the modeled period range of 3–20more » s shows that in general, the 3D velocity model performs well. Areas in which the model needs improvements are located mainly in the central part of the Kura basin and in the Caspian Sea coastal areas. Comparisons of simulated ground motion using our 3D velocity model and corresponding 1D regional velocity model were used to locate areas with strong 3D wave propagation effects. In areas with complex underground structure, the 1D model fails to produce the observed ground motion amplitude and duration, and spatial extend of ground motion amplification caused by wave propagation effects.« less

High-fidelity simulation capability for virtual testing of seismic and acoustic sensors

NASA Astrophysics Data System (ADS)

Wilson, D. Keith; Moran, Mark L.; Ketcham, Stephen A.; Lacombe, James; Anderson, Thomas S.; Symons, Neill P.; Aldridge, David F.; Marlin, David H.; Collier, Sandra L.; Ostashev, Vladimir E.

2005-05-01

This paper describes development and application of a high-fidelity, seismic/acoustic simulation capability for battlefield sensors. The purpose is to provide simulated sensor data so realistic that they cannot be distinguished by experts from actual field data. This emerging capability provides rapid, low-cost trade studies of unattended ground sensor network configurations, data processing and fusion strategies, and signatures emitted by prototype vehicles. There are three essential components to the modeling: (1) detailed mechanical signature models for vehicles and walkers, (2) high-resolution characterization of the subsurface and atmospheric environments, and (3) state-of-the-art seismic/acoustic models for propagating moving-vehicle signatures through realistic, complex environments. With regard to the first of these components, dynamic models of wheeled and tracked vehicles have been developed to generate ground force inputs to seismic propagation models. Vehicle models range from simple, 2D representations to highly detailed, 3D representations of entire linked-track suspension systems. Similarly detailed models of acoustic emissions from vehicle engines are under development. The propagation calculations for both the seismics and acoustics are based on finite-difference, time-domain (FDTD) methodologies capable of handling complex environmental features such as heterogeneous geologies, urban structures, surface vegetation, and dynamic atmospheric turbulence. Any number of dynamic sources and virtual sensors may be incorporated into the FDTD model. The computational demands of 3D FDTD simulation over tactical distances require massively parallel computers. Several example calculations of seismic/acoustic wave propagation through complex atmospheric and terrain environments are shown.

Influence of refractive condition on retinal vasculature complexity in younger subjects.

PubMed

Azemin, Mohd Zulfaezal Che; Daud, Norsyazwani Mohamad; Ab Hamid, Fadilah; Zahari, Ilyanoon; Sapuan, Abdul Halim

2014-01-01

The aim of this study was to compare the retinal vasculature complexity between emmetropia, and myopia in younger subjects. A total of 82 patients (24.12 ± 1.25 years) with two types of refractive conditions, myopia and emmetropia were enrolled in this study. Refraction data were converted to spherical equivalent refraction. These retinal images (right eyes) were obtained from NAVIS Lite Image Filing System and the vasculature complexity was measured by fractal dimension (D f ), quantified using a computer software following a standardized protocol. There was a significant difference (P < 0.05) in the value of D f between emmetropic (1.5666 ± 0.0160) and myopic (1.5588 ± 0.0142) groups. A positive correlation (rho = 0.260, P < 0.05) between the D f and the spherical equivalent refraction was detected in this study. Using a linear model, it was estimated that 6.7% of the variation in D f could be explained by spherical equivalent refraction. This study provides valuable findings about the effect of moderate to high myopia on the fractal dimension of the retinal vasculature network. These results show that myopic refraction in younger subjects was associated with a decrease in D f , suggesting a loss of retinal vessel density with moderate to high myopia.

Advanced Multivariate Inversion Techniques for High Resolution 3D Geophysical Modeling

DTIC Science & Technology

2011-09-01

of seismic ambient noise – has been used to image crustal Vs variation with a lateral resolution upward of 100 km either on regional or on sub...to East Africa, we solve for velocity structure in an area with less lateral heterogeneity but great tectonic complexity. To increase the...demonstrate correlation with crustal geology. Figure 1 shows the 3D S-wave velocity model obtained from the joint inversion. The low-velocity anomaly

Analysis of the binding sites of vitamin D 1α-hydroxylase (CYP27B1) and vitamin D 24-hydroxylase (CYP24A1) for the design of selective CYP24A1 inhibitors: Homology modelling, molecular dynamics simulations and identification of key binding requirements.

PubMed

Taban, Ismail M; Zhu, Jinge; DeLuca, Hector F; Simons, Claire

2017-10-15

A homology model of human CYP27B1 was built using MOE and was further optimised by molecular dynamics simulations of the hCYP27B1 homology model and a hCYP27B1-SDZ-88357 complex. Docking results from the hCYP27B1-SDZ-88357 complex showed amino acids Arg107, Asn387 and Asp320 have an important role in binding interaction, with Asp320 part of the important acid-alcohol pair situated in the I-helix with the conserved sequence (A/G) GX (E/D) (T/S), which assumes an essential role in the binding of an oxygen molecule for catalysis. Additional docking experiments with selective hCYP27B1 or hCYP24A1 inhibitors using both the hCYP27B1 model and a triple mutant hCYP24A1 model provided further support for the importance of H-bonding interactions with the three identified active site amino acids. To confirm the role of Arg107, Asn387 and Asp320 in the active site of hCYP27B1 compounds were designed that would form H-bonding interactions, as determined from docking experiments with the hCYP27B1 model. Subsequent synthesis and CYP24A1 and CYP27B1 enzyme assays of the designed compounds 1a and 1b showed a∼5-fold selectivity for CYP27B1 confirming the importance of Asp320 in particular and also Asn387 and Arg107 as important amino acids for CYP27B1 inhibitory activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

3D DOSY-TROSY to determine the translational diffusion coefficient of large protein complexes.

PubMed

Didenko, Tatiana; Boelens, Rolf; Rüdiger, Stefan G D

2011-01-01

The translational diffusion coefficient is a sensitive parameter to probe conformational changes in proteins and protein-protein interactions. Pulsed-field gradient NMR spectroscopy allows one to measure the translational diffusion with high accuracy. Two-dimensional (2D) heteronuclear NMR spectroscopy combined with diffusion-ordered spectroscopy (DOSY) provides improved resolution and therefore selectivity when compared with a conventional 1D readout. Here, we show that a combination of selective isotope labelling, 2D ¹H-¹³C methyl-TROSY (transverse relaxation-optimised spectroscopy) and DOSY allows one to study diffusion properties of large protein complexes. We propose that a 3D DOSY-heteronuclear multiple quantum coherence (HMQC) pulse sequence, that uses the TROSY effect of the HMQC sequence for ¹³C methyl-labelled proteins, is highly suitable for measuring the diffusion coefficient of large proteins. We used the 20 kDa co-chaperone p23 as model system to test this 3D DOSY-TROSY technique under various conditions. We determined the diffusion coefficient of p23 in viscous solutions, mimicking large complexes of up to 200 kDa. We found the experimental data to be in excellent agreement with theoretical predictions. To demonstrate the use for complex formation, we applied this technique to record the formation of a complex of p23 with the molecular chaperone Hsp90, which is around 200 kDa. We anticipate that 3D DOSY-TROSY will be a useful tool to study conformational changes in large protein complexes.

Nanostructures formed by cyclodextrin covered procainamide through supramolecular self assembly - Spectral and molecular modeling study

NASA Astrophysics Data System (ADS)

Rajendiran, N.; Mohandoss, T.; Sankaranarayanan, R. K.

2015-02-01

Inclusion complexation behavior of procainamide (PCA) with two cyclodextrins (α-CD and β-CD) were analyzed by absorption, fluorescence, scanning electron microscope (SEM), transmission electron microscope (TEM), Raman image, FT-IR, differential scanning colorimeter (DSC), Powder X ray diffraction (XRD) and 1H NMR. Blue shift was observed in β-CD whereas no significant spectral shift observed in α-CD. The inclusion complex formation results suggest that water molecules also present in the inside of the CD cavity. The present study revealed that the phenyl ring of the PCA drug is entrapped in the CD cavity. Cyclodextrin studies show that PCA forms 1:2 inclusion complex with α-CD and β-CD. PCA:α-CD complex form nano-sized particles (46 nm) and PCA:β-CD complex form self-assembled to micro-sized tubular structures. The shape-shifting of 2D nanosheets into 1D microtubes by simple rolling mechanism were analysed by micro-Raman and TEM images. Thermodynamic parameters (ΔH, ΔG and ΔS) of inclusion process were determined from semiempirical PM3 calculations.

Heteroreceptor Complexes Formed by Dopamine D1, Histamine H3, and N-Methyl-D-Aspartate Glutamate Receptors as Targets to Prevent Neuronal Death in Alzheimer's Disease.

PubMed

Rodríguez-Ruiz, Mar; Moreno, Estefanía; Moreno-Delgado, David; Navarro, Gemma; Mallol, Josefa; Cortés, Antonio; Lluís, Carme; Canela, Enric I; Casadó, Vicent; McCormick, Peter J; Franco, Rafael

2017-08-01

Alzheimer's disease (AD) is a neurodegenerative disorder causing progressive memory loss and cognitive dysfunction. Anti-AD strategies targeting cell receptors consider them as isolated units. However, many cell surface receptors cooperate and physically contact each other forming complexes having different biochemical properties than individual receptors. We here report the discovery of dopamine D 1 , histamine H 3 , and N-methyl-D-aspartate (NMDA) glutamate receptor heteromers in heterologous systems and in rodent brain cortex. Heteromers were detected by co-immunoprecipitation and in situ proximity ligation assays (PLA) in the rat cortex where H 3 receptor agonists, via negative cross-talk, and H 3 receptor antagonists, via cross-antagonism, decreased D 1 receptor agonist signaling determined by ERK1/2 or Akt phosphorylation, and counteracted D 1 receptor-mediated excitotoxic cell death. Both D 1 and H 3 receptor antagonists also counteracted NMDA toxicity suggesting a complex interaction between NMDA receptors and D 1 -H 3 receptor heteromer function. Likely due to heteromerization, H 3 receptors act as allosteric regulator for D 1 and NMDA receptors. By bioluminescence resonance energy transfer (BRET), we demonstrated that D 1 or H 3 receptors form heteromers with NR1A/NR2B NMDA receptor subunits. D 1 -H 3 -NMDA receptor complexes were confirmed by BRET combined with fluorescence complementation. The endogenous expression of complexes in mouse cortex was determined by PLA and similar expression was observed in wild-type and APP/PS1 mice. Consistent with allosteric receptor-receptor interactions within the complex, H 3 receptor antagonists reduced NMDA or D 1 receptor-mediated excitotoxic cell death in cortical organotypic cultures. Moreover, H 3 receptor antagonists reverted the toxicity induced by ß 1-42 -amyloid peptide. Thus, histamine H 3 receptors in D 1 -H 3 -NMDA heteroreceptor complexes arise as promising targets to prevent neurodegeneration.

Rapid-mix and chemical quench studies of ferredoxin-reduced stearoyl-acyl carrier protein desaturase.

PubMed

Lyle, Karen S; Haas, Jeffrey A; Fox, Brian G

2003-05-20

Stearoyl-ACP Delta9 desaturase (Delta9D) catalyzes the NADPH- and O(2)-dependent insertion of a cis double bond between the C9 and C10 positions of stearoyl-ACP (18:0-ACP) to produce oleoyl-ACP (18:1-ACP). This work revealed the ability of reduced [2Fe-2S] ferredoxin (Fd) to act as a catalytically competent electron donor during the rapid conversion of 18:0-ACP into 18:1-ACP. Experiments on the order of addition for substrate and reduced Fd showed high conversion of 18:0-ACP to 18:1-ACP (approximately 95% per Delta9D active site in a single turnover) when 18:0-ACP was added prior to reduced Fd. Reactions of the prereduced enzyme-substrate complex with O(2) and the oxidized enzyme-substrate complex with reduced Fd were studied by rapid-mix and chemical quench methods. For reaction of the prereduced enzyme-substrate complex, an exponential burst phase (k(burst) = 95 s(-1)) of product formation accounted for approximately 90% of the turnover expected for one subunit in the dimeric protein. This rapid phase was followed by a slower phase (k(linear) = 4.0 s(-1)) of product formation corresponding to the turnover expected from the second subunit. For reaction of the oxidized enzyme-substrate complex with excess reduced Fd, a slower, linear rate (k(obsd) = 3.4 s(-1)) of product formation was observed over approximately 1.5 turnovers per Delta9D active site potentially corresponding to a third phase of reaction. An analysis of the deuterium isotope effect on the two rapid-mix reaction sequences revealed only a modest effect on k(burst) ((D)k(burst) approximately 1.5) and k(linear) (D)k(linear) approximately 1.4), indicating C-H bond cleavage does not contribute significantly to the rate-limiting steps of pre-steady-state catalysis. These results were used to assemble and evaluate a minimal kinetic model for Delta9D catalysis.

dSet1 Is the Main H3K4 Di- and Tri-Methyltransferase Throughout Drosophila Development

PubMed Central

Hallson, Graham; Hollebakken, Robert E.; Li, Taosui; Syrzycka, Monika; Kim, Inho; Cotsworth, Shawn; Fitzpatrick, Kathleen A.; Sinclair, Donald A. R.; Honda, Barry M.

2012-01-01

In eukaryotes, the post-translational addition of methyl groups to histone H3 lysine 4 (H3K4) plays key roles in maintenance and establishment of appropriate gene expression patterns and chromatin states. We report here that an essential locus within chromosome 3L centric heterochromatin encodes the previously uncharacterized Drosophila melanogaster ortholog (dSet1, CG40351) of the Set1 H3K4 histone methyltransferase (HMT). Our results suggest that dSet1 acts as a “global” or general H3K4 di- and trimethyl HMT in Drosophila. Levels of H3K4 di- and trimethylation are significantly reduced in dSet1 mutants during late larval and post-larval stages, but not in animals carrying mutations in genes encoding other well-characterized H3K4 HMTs such as trr, trx, and ash1. The latter results suggest that Trr, Trx, and Ash1 may play more specific roles in regulating key cellular targets and pathways and/or act as global H3K4 HMTs earlier in development. In yeast and mammalian cells, the HMT activity of Set1 proteins is mediated through an evolutionarily conserved protein complex known as Complex of Proteins Associated with Set1 (COMPASS). We present biochemical evidence that dSet1 interacts with members of a putative Drosophila COMPASS complex and genetic evidence that these members are functionally required for H3K4 methylation. Taken together, our results suggest that dSet1 is responsible for the bulk of H3K4 di- and trimethylation throughout Drosophila development, thus providing a model system for better understanding the requirements for and functions of these modifications in metazoans. PMID:22048023

Structure, Subunit Topology, and Actin-binding Activity of the Arp2/3 Complex from Acanthamoeba

PubMed Central

Mullins, R. Dyche; Stafford, Walter F.; Pollard, Thomas D.

1997-01-01

The Arp2/3 complex, first isolated from Acanthamoeba castellani by affinity chromatography on profilin, consists of seven polypeptides; two actinrelated proteins, Arp2 and Arp3; and five apparently novel proteins, p40, p35, p19, p18, and p14 (Machesky et al., 1994). The complex is homogeneous by hydrodynamic criteria with a Stokes' radius of 5.3 nm by gel filtration, sedimentation coefficient of 8.7 S, and molecular mass of 197 kD by analytical ultracentrifugation. The stoichiometry of the subunits is 1:1:1:1:1:1:1, indicating the purified complex contains one copy each of seven polypeptides. In electron micrographs, the complex has a bilobed or horseshoe shape with outer dimensions of ∼13 × 10 nm, and mathematical models of such a shape and size are consistent with the measured hydrodynamic properties. Chemical cross-linking with a battery of cross-linkers of different spacer arm lengths and chemical reactivities identify the following nearest neighbors within the complex: Arp2 and p40; Arp2 and p35; Arp3 and p35; Arp3 and either p18 or p19; and p19 and p14. By fluorescent antibody staining with anti-p40 and -p35, the complex is concentrated in the cortex of the ameba, especially in linear structures, possibly actin filament bundles, that lie perpendicular to the leading edge. Purified Arp2/3 complex binds actin filaments with a K d of 2.3 μM and a stoichiometry of approximately one complex molecule per actin monomer. In electron micrographs of negatively stained samples, Arp2/3 complex decorates the sides of actin filaments. EDC/NHS cross-links actin to Arp3, p35, and a low molecular weight subunit, p19, p18, or p14. We propose structural and topological models for the Arp2/3 complex and suggest that affinity for actin filaments accounts for the localization of complex subunits to actinrich regions of Acanthamoeba. PMID:9015304

Resolution analysis of finite fault source inversion using one- and three-dimensional Green's functions 1. Strong motions

USGS Publications Warehouse

Graves, R.W.; Wald, D.J.

2001-01-01

We develop a methodology to perform finite fault source inversions from strong motion data using Green's functions (GFs) calculated for a three-dimensional (3-D) velocity structure. The 3-D GFs are calculated numerically by inserting body forces at each of the strong motion sites and then recording the resulting strains along the target fault surface. Using reciprocity, these GFs can be recombined to represent the ground motion at each site for any (heterogeneous) slip distribution on the fault. The reciprocal formulation significantly reduces the required number of 3-D finite difference computations to at most 3NS, where NS is the number of strong motion sites used in the inversion. Using controlled numerical resolution tests, we have examined the relative importance of accurate GFs for finite fault source inversions which rely on near-source ground motions. These experiments use both 1-D and 3-D GFs in inversions for hypothetical rupture models in order (1) to analyze the ability of the 3-D methodology to resolve trade-offs between complex source phenomena and 3-D path effects, (2) to address the sensitivity of the inversion results to uncertainties in the 3-D velocity structure, and (3) to test the adequacy of the 1-D GF method when propagation effects are known to be three-dimensional. We find that given "data" from a prescribed 3-D Earth structure, the use of well-calibrated 3-D GFs in the inversion provides very good resolution of the assumed slip distribution, thus adequately separating source and 3-D propagation effects. In contrast, using a set of inexact 3-D GFs or a set of hybrid 1-D GFs allows only partial recovery of the slip distribution. These findings suggest that in regions of complex geology the use of well-calibrated 3-D GFs has the potential for increased resolution of the rupture process relative to 1-D GFs. However, realizing this full potential requires that the 3-D velocity model and associated GFs should be carefully validated against the true 3-D Earth structure before performing the inverse problem with actual data. Copyright 2001 by the American Geophysical Union.

3D MRI Modeling of Thin and Spatially Complex Soft Tissue Structures without Shrinkage: Lamprey Myosepta as an Example.

PubMed

Wood, Bradley M; Jia, Guang; Carmichael, Owen; McKlveen, Kevin; Homberger, Dominique G

2018-05-12

3D imaging techniques enable the non-destructive analysis and modeling of complex structures. Among these, MRI exhibits good soft tissue contrast, but is currently less commonly used for non-clinical research than x-ray CT, even though the latter requires contrast-staining that shrinks and distorts soft tissues. When the objective is the creation of a realistic and complete 3D model of soft tissue structures, MRI data are more demanding to acquire and visualize and require extensive post-processing because they comprise non-cubic voxels with dimensions that represent a trade-off between tissue contrast and image resolution. Therefore, thin soft tissue structures with complex spatial configurations are not always visible in a single MRI dataset, so that standard segmentation techniques are not sufficient for their complete visualization. By using the example of the thin and spatially complex connective tissue myosepta in lampreys, we developed a workflow protocol for the selection of the appropriate parameters for the acquisition of MRI data and for the visualization and 3D modeling of soft tissue structures. This protocol includes a novel recursive segmentation technique for supplementing missing data in one dataset with data from another dataset to produce realistic and complete 3D models. Such 3D models are needed for the modeling of dynamic processes, such as the biomechanics of fish locomotion. However, our methodology is applicable to the visualization of any thin soft tissue structures with complex spatial configurations, such as fasciae, aponeuroses, and small blood vessels and nerves, for clinical research and the further exploration of tensegrity. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

1D-3D hybrid modeling-from multi-compartment models to full resolution models in space and time.

PubMed

Grein, Stephan; Stepniewski, Martin; Reiter, Sebastian; Knodel, Markus M; Queisser, Gillian

2014-01-01

Investigation of cellular and network dynamics in the brain by means of modeling and simulation has evolved into a highly interdisciplinary field, that uses sophisticated modeling and simulation approaches to understand distinct areas of brain function. Depending on the underlying complexity, these models vary in their level of detail, in order to cope with the attached computational cost. Hence for large network simulations, single neurons are typically reduced to time-dependent signal processors, dismissing the spatial aspect of each cell. For single cell or networks with relatively small numbers of neurons, general purpose simulators allow for space and time-dependent simulations of electrical signal processing, based on the cable equation theory. An emerging field in Computational Neuroscience encompasses a new level of detail by incorporating the full three-dimensional morphology of cells and organelles into three-dimensional, space and time-dependent, simulations. While every approach has its advantages and limitations, such as computational cost, integrated and methods-spanning simulation approaches, depending on the network size could establish new ways to investigate the brain. In this paper we present a hybrid simulation approach, that makes use of reduced 1D-models using e.g., the NEURON simulator-which couples to fully resolved models for simulating cellular and sub-cellular dynamics, including the detailed three-dimensional morphology of neurons and organelles. In order to couple 1D- and 3D-simulations, we present a geometry-, membrane potential- and intracellular concentration mapping framework, with which graph- based morphologies, e.g., in the swc- or hoc-format, are mapped to full surface and volume representations of the neuron and computational data from 1D-simulations can be used as boundary conditions for full 3D simulations and vice versa. Thus, established models and data, based on general purpose 1D-simulators, can be directly coupled to the emerging field of fully resolved, highly detailed 3D-modeling approaches. We present the developed general framework for 1D/3D hybrid modeling and apply it to investigate electrically active neurons and their intracellular spatio-temporal calcium dynamics.

Semi-classical approach to compute RABBITT traces in multi-dimensional complex field distributions.

PubMed

Lucchini, M; Ludwig, A; Kasmi, L; Gallmann, L; Keller, U

2015-04-06

We present a semi-classical model to calculate RABBITT (Reconstruction of Attosecond Beating By Interference of Two-photon Transitions) traces in the presence of a reference infrared field with a complex two-dimensional (2D) spatial distribution. The evolution of the electron spectra as a function of the pump-probe delay is evaluated starting from the solution of the classical equation of motion and incorporating the quantum phase acquired by the electron during the interaction with the infrared field. The total response to an attosecond pulse train is then evaluated by a coherent sum of the contributions generated by each individual attosecond pulse in the train. The flexibility of this model makes it possible to calculate spectrograms from non-trivial 2D field distributions. After confirming the validity of the model in a simple 1D case, we extend the discussion to describe the probe-induced phase in photo-emission experiments on an ideal metallic surface.

The 3-D structure of the Somma-Vesuvius volcanic complex (Italy) inferred from new and historic gravimetric data.

PubMed

Linde, Niklas; Ricci, Tullio; Baron, Ludovic; Shakas, Alexis; Berrino, Giovanna

2017-08-16

Existing 3-D density models of the Somma-Vesuvius volcanic complex (SVVC), Italy, largely disagree. Despite the scientific and socioeconomic importance of Vesuvius, there is no reliable 3-D density model of the SVVC. A considerable uncertainty prevails concerning the presence (or absence) of a dense body underlying the Vesuvius crater (1944 eruption) that is implied from extensive seismic investigations. We have acquired relative gravity measurements at 297 stations, including measurements in difficult-to-access areas (e.g., the first-ever measurements in the crater). In agreement with seismic investigations, the simultaneous inversion of these and historic data resolves a high-density body that extends from the surface of the Vesuvius crater down to depths that exceed 2 km. A 1.5-km radius horseshoe-shaped dense feature (open in the southwestern sector) enforces the existing model of groundwater circulation within the SVVC. Based on its volcano-tectonic evolution, we interpret volcanic structures that have never been imaged before.

An evaluative model of system performance in manned teleoperational systems

NASA Technical Reports Server (NTRS)

Haines, Richard F.

1989-01-01

Manned teleoperational systems are used in aerospace operations in which humans must interact with machines remotely. Manual guidance of remotely piloted vehicles, controling a wind tunnel, carrying out a scientific procedure remotely are examples of teleoperations. A four input parameter throughput (Tp) model is presented which can be used to evaluate complex, manned, teleoperations-based systems and make critical comparisons among candidate control systems. The first two parameters of this model deal with nominal (A) and off-nominal (B) predicted events while the last two focus on measured events of two types, human performance (C) and system performance (D). Digital simulations showed that the expression A(1-B)/C+D) produced the greatest homogeneity of variance and distribution symmetry. Results from a recently completed manned life science telescience experiment will be used to further validate the model. Complex, interacting teleoperational systems may be systematically evaluated using this expression much like a computer benchmark is used.

Plasma and Electro-energetic Physics

DTIC Science & Technology

2012-03-07

Dynamical Equations (with complex surfaces ): Relativistic Lorentz Force Law for relativistic momentum p and velocity u: tDcJcH tBcE   /)/1()/4...0.1-1 s • 3D, high-fidelity, parallel modeling of high energy density fields and particles in complex geometry with some surface effects...cathodes (500 µm separation) Tang, AFRL/RD 12 DISTRIBUTION A: Approved for public release; distribution is unlimited. ICEPIC simulations Equipotential

Sensitivity of Above-Ground Biomass Estimates to Height-Diameter Modelling in Mixed-Species West African Woodlands

PubMed Central

Aynekulu, Ermias; Pitkänen, Sari; Packalen, Petteri

2016-01-01

It has been suggested that above-ground biomass (AGB) inventories should include tree height (H), in addition to diameter (D). As H is a difficult variable to measure, H-D models are commonly used to predict H. We tested a number of approaches for H-D modelling, including additive terms which increased the complexity of the model, and observed how differences in tree-level predictions of H propagated to plot-level AGB estimations. We were especially interested in detecting whether the choice of method can lead to bias. The compared approaches listed in the order of increasing complexity were: (B0) AGB estimations from D-only; (B1) involving also H obtained from a fixed-effects H-D model; (B2) involving also species; (B3) including also between-plot variability as random effects; and (B4) involving multilevel nested random effects for grouping plots in clusters. In light of the results, the modelling approach affected the AGB estimation significantly in some cases, although differences were negligible for some of the alternatives. The most important differences were found between including H or not in the AGB estimation. We observed that AGB predictions without H information were very sensitive to the environmental stress parameter (E), which can induce a critical bias. Regarding the H-D modelling, the most relevant effect was found when species was included as an additive term. We presented a two-step methodology, which succeeded in identifying the species for which the general H-D relation was relevant to modify. Based on the results, our final choice was the single-level mixed-effects model (B3), which accounts for the species but also for the plot random effects reflecting site-specific factors such as soil properties and degree of disturbance. PMID:27367857

Complexity growth in minimal massive 3D gravity

NASA Astrophysics Data System (ADS)

Qaemmaqami, Mohammad M.

2018-01-01

We study the complexity growth by using "complexity =action " (CA) proposal in the minimal massive 3D gravity (MMG) model which is proposed for resolving the bulk-boundary clash problem of topologically massive gravity (TMG). We observe that the rate of the complexity growth for Banados-Teitelboim-Zanelli (BTZ) black hole saturates the proposed bound by physical mass of the BTZ black hole in the MMG model, when the angular momentum parameter and the inner horizon of black hole goes to zero.

3D printing the pterygopalatine fossa: a negative space model of a complex structure.

PubMed

Bannon, Ross; Parihar, Shivani; Skarparis, Yiannis; Varsou, Ourania; Cezayirli, Enis

2018-02-01

The pterygopalatine fossa is one of the most complex anatomical regions to understand. It is poorly visualized in cadaveric dissection and most textbooks rely on schematic depictions. We describe our approach to creating a low-cost, 3D model of the pterygopalatine fossa, including its associated canals and foramina, using an affordable "desktop" 3D printer. We used open source software to create a volume render of the pterygopalatine fossa from axial slices of a head computerised tomography scan. These data were then exported to a 3D printer to produce an anatomically accurate model. The resulting 'negative space' model of the pterygopalatine fossa provides a useful and innovative aid for understanding the complex anatomical relationships of the pterygopalatine fossa. This model was designed primarily for medical students; however, it will also be of interest to postgraduates in ENT, ophthalmology, neurosurgery, and radiology. The technical process described may be replicated by other departments wishing to develop their own anatomical models whilst incurring minimal costs.

My Corporis Fabrica Embryo: An ontology-based 3D spatio-temporal modeling of human embryo development.

PubMed

Rabattu, Pierre-Yves; Massé, Benoit; Ulliana, Federico; Rousset, Marie-Christine; Rohmer, Damien; Léon, Jean-Claude; Palombi, Olivier

2015-01-01

Embryology is a complex morphologic discipline involving a set of entangled mechanisms, sometime difficult to understand and to visualize. Recent computer based techniques ranging from geometrical to physically based modeling are used to assist the visualization and the simulation of virtual humans for numerous domains such as surgical simulation and learning. On the other side, the ontology-based approach applied to knowledge representation is more and more successfully adopted in the life-science domains to formalize biological entities and phenomena, thanks to a declarative approach for expressing and reasoning over symbolic information. 3D models and ontologies are two complementary ways to describe biological entities that remain largely separated. Indeed, while many ontologies providing a unified formalization of anatomy and embryology exist, they remain only descriptive and make the access to anatomical content of complex 3D embryology models and simulations difficult. In this work, we present a novel ontology describing the development of the human embryology deforming 3D models. Beyond describing how organs and structures are composed, our ontology integrates a procedural description of their 3D representations, temporal deformation and relations with respect to their developments. We also created inferences rules to express complex connections between entities. It results in a unified description of both the knowledge of the organs deformation and their 3D representations enabling to visualize dynamically the embryo deformation during the Carnegie stages. Through a simplified ontology, containing representative entities which are linked to spatial position and temporal process information, we illustrate the added-value of such a declarative approach for interactive simulation and visualization of 3D embryos. Combining ontologies and 3D models enables a declarative description of different embryological models that capture the complexity of human developmental anatomy. Visualizing embryos with 3D geometric models and their animated deformations perhaps paves the way towards some kind of hypothesis-driven application. These can also be used to assist the learning process of this complex knowledge. http://www.mycorporisfabrica.org/.

Three-dimensional-printed cardiac prototypes aid surgical decision-making and preoperative planning in selected cases of complex congenital heart diseases: Early experience and proof of concept in a resource-limited environment.

PubMed

Kappanayil, Mahesh; Koneti, Nageshwara Rao; Kannan, Rajesh R; Kottayil, Brijesh P; Kumar, Krishna

2017-01-01

Three-dimensional. (3D) printing is an innovative manufacturing process that allows computer-assisted conversion of 3D imaging data into physical "printouts" Healthcare applications are currently in evolution. The objective of this study was to explore the feasibility and impact of using patient-specific 3D-printed cardiac prototypes derived from high-resolution medical imaging data (cardiac magnetic resonance imaging/computed tomography [MRI/CT]) on surgical decision-making and preoperative planning in selected cases of complex congenital heart diseases (CHDs). Five patients with complex CHD with previously unresolved management decisions were chosen. These included two patients with complex double-outlet right ventricle, two patients with criss-cross atrioventricular connections, and one patient with congenitally corrected transposition of great arteries with pulmonary atresia. Cardiac MRI was done for all patients, cardiac CT for one; specific surgical challenges were identified. Volumetric data were used to generate patient-specific 3D models. All cases were reviewed along with their 3D models, and the impact on surgical decision-making and preoperative planning was assessed. Accurate life-sized 3D cardiac prototypes were successfully created for all patients. The models enabled radically improved 3D understanding of anatomy, identification of specific technical challenges, and precise surgical planning. Augmentation of existing clinical and imaging data by 3D prototypes allowed successful execution of complex surgeries for all five patients, in accordance with the preoperative planning. 3D-printed cardiac prototypes can radically assist decision-making, planning, and safe execution of complex congenital heart surgery by improving understanding of 3D anatomy and allowing anticipation of technical challenges.

Two supramolecular complexes based on polyoxometalates and Co-EDTA units via covalent connection or non-covalent interaction

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

Teng, Chunlin; Xiao, Hanxi; Cai, Qing

Two new 3D network organic-inorganic hybrid supramolecular complexes ([Na{sub 6}(CoEDTA){sub 2}(H{sub 2}O){sub 13}]·(H{sub 2}SiW{sub 12}O{sub 40})·xH{sub 2}O)n (1) and [CoH{sub 4}EDTA(H{sub 2}O)]{sub 2}(SiW{sub 12}O{sub 40})·15H{sub 2}O (2) (H{sub 4}EDTA=Ethylenediamine tetraacetic acid) have been successfully synthesized by solution method, and characterized by infrared spectrum (IR), thermogravimetric-differential thermal analysis (TG-DTA), cyclic voltammetry (CV) and single{sup −}crystal X-ray diffraction (XRD). Both of the complexes are the supramolecules, but with different liking mode, they are two representative models of supramolecule. complex (1) is a 3D infinite network supramolecular coordination polymer with a rare multi-metal sturcture of sodium-cobalt-containing, which is mainly linked through coordinate-covalent bonds.more » While complex (2) is normal supramolecule, which linked by non-covalent interactions, such as H-bonding interaction, electrostatic interaction and van der waals force. Both of complex (1) and (2) exhibit good catalytic activities for catalytic oxidation of methanol, when the initial concentration of methanol is 3.0 g m{sup −3}, flow rate is 10 mL min{sup −1}, and the quality of catalyst is 0.2 g, for complex (1) and complex (2) the maximum elimination rates of methanol are 85% (150 °C) and 92% (120 °C), respectively. - Graphical abstract: Two new organic-inorganic hybrid supramolecular complexes based on Co-EDTA, and Keggin polyanions have been successfully synthesized with different pH value by solution method. They are attributed to two representative models of supramolecule. Complex(1) is an infinite coordination polymer with a rare multi-metal sturcture of sodium-cobalt-containing, which is mainly linked through covalent bonds. Complex (2) is a normal supramolecule, which linked by non-covalent interactions of H-bonding interaction, electrostatic interaction and van der waals force. - Highlights: • Two supramolecules are linked by covalent or non-covalent interactions. • They are attributed to two representative models of supramolecule. • A rare multi-metal infinite supramolecular coordination polymer was formed. • They exhibit good catalytic activities for catalytic oxidation of methanol.« less

Utility and Scope of Rapid Prototyping in Patients with Complex Muscular Ventricular Septal Defects or Double-Outlet Right Ventricle: Does it Alter Management Decisions?

PubMed

Bhatla, Puneet; Tretter, Justin T; Ludomirsky, Achi; Argilla, Michael; Latson, Larry A; Chakravarti, Sujata; Barker, Piers C; Yoo, Shi-Joon; McElhinney, Doff B; Wake, Nicole; Mosca, Ralph S

2017-01-01

Rapid prototyping facilitates comprehension of complex cardiac anatomy. However, determining when this additional information proves instrumental in patient management remains a challenge. We describe our experience with patient-specific anatomic models created using rapid prototyping from various imaging modalities, suggesting their utility in surgical and interventional planning in congenital heart disease (CHD). Virtual and physical 3-dimensional (3D) models were generated from CT or MRI data, using commercially available software for patients with complex muscular ventricular septal defects (CMVSD) and double-outlet right ventricle (DORV). Six patients with complex anatomy and uncertainty of the optimal management strategy were included in this study. The models were subsequently used to guide management decisions, and the outcomes reviewed. 3D models clearly demonstrated the complex intra-cardiac anatomy in all six patients and were utilized to guide management decisions. In the three patients with CMVSD, one underwent successful endovascular device closure following a prior failed attempt at transcatheter closure, and the other two underwent successful primary surgical closure with the aid of 3D models. In all three cases of DORV, the models provided better anatomic delineation and additional information that altered or confirmed the surgical plan. Patient-specific 3D heart models show promise in accurately defining intra-cardiac anatomy in CHD, specifically CMVSD and DORV. We believe these models improve understanding of the complex anatomical spatial relationships in these defects and provide additional insight for pre/intra-interventional management and surgical planning.

Scalable Multi-Platform Distribution of Spatial 3d Contents

NASA Astrophysics Data System (ADS)

Klimke, J.; Hagedorn, B.; Döllner, J.

2013-09-01

Virtual 3D city models provide powerful user interfaces for communication of 2D and 3D geoinformation. Providing high quality visualization of massive 3D geoinformation in a scalable, fast, and cost efficient manner is still a challenging task. Especially for mobile and web-based system environments, software and hardware configurations of target systems differ significantly. This makes it hard to provide fast, visually appealing renderings of 3D data throughout a variety of platforms and devices. Current mobile or web-based solutions for 3D visualization usually require raw 3D scene data such as triangle meshes together with textures delivered from server to client, what makes them strongly limited in terms of size and complexity of the models they can handle. In this paper, we introduce a new approach for provisioning of massive, virtual 3D city models on different platforms namely web browsers, smartphones or tablets, by means of an interactive map assembled from artificial oblique image tiles. The key concept is to synthesize such images of a virtual 3D city model by a 3D rendering service in a preprocessing step. This service encapsulates model handling and 3D rendering techniques for high quality visualization of massive 3D models. By generating image tiles using this service, the 3D rendering process is shifted from the client side, which provides major advantages: (a) The complexity of the 3D city model data is decoupled from data transfer complexity (b) the implementation of client applications is simplified significantly as 3D rendering is encapsulated on server side (c) 3D city models can be easily deployed for and used by a large number of concurrent users, leading to a high degree of scalability of the overall approach. All core 3D rendering techniques are performed on a dedicated 3D rendering server, and thin-client applications can be compactly implemented for various devices and platforms.

Development of 7TM receptor-ligand complex models using ligand-biased, semi-empirical helix-bundle repacking in torsion space: application to the agonist interaction of the human dopamine D2 receptor.

PubMed

Malo, Marcus; Persson, Ronnie; Svensson, Peder; Luthman, Kristina; Brive, Lars

2013-03-01

Prediction of 3D structures of membrane proteins, and of G-protein coupled receptors (GPCRs) in particular, is motivated by their importance in biological systems and the difficulties associated with experimental structure determination. In the present study, a novel method for the prediction of 3D structures of the membrane-embedded region of helical membrane proteins is presented. A large pool of candidate models are produced by repacking of the helices of a homology model using Monte Carlo sampling in torsion space, followed by ranking based on their geometric and ligand-binding properties. The trajectory is directed by weak initial restraints to orient helices towards the original model to improve computation efficiency, and by a ligand to guide the receptor towards a chosen conformational state. The method was validated by construction of the β1 adrenergic receptor model in complex with (S)-cyanopindolol using bovine rhodopsin as template. In addition, models of the dopamine D2 receptor were produced with the selective and rigid agonist (R)-N-propylapomorphine ((R)-NPA) present. A second quality assessment was implemented by evaluating the results from docking of a library of 29 ligands with known activity, which further discriminated between receptor models. Agonist binding and recognition by the dopamine D2 receptor is interpreted using the 3D structure model resulting from the approach. This method has a potential for modeling of all types of helical transmembrane proteins for which a structural template with sequence homology sufficient for homology modeling is not available or is in an incorrect conformational state, but for which sufficient empirical information is accessible.

Forbidden territories in the string landscape

NASA Astrophysics Data System (ADS)

Kumar, Alok; Mukhopadhyay, Subir; Ray, Koushik

2007-12-01

Problems of stabilizing moduli of the type-IIB string theory on toroidal orientifolds T6/Z2, in presence of worldvolume fluxes on various D-branes, are considered. For Z2 actions, introducing either O9 or O3 planes, we rule out the possibility of moduli stabilization in a wide class of models with Script N = 1 supersymmetry, characterized by the type of fluxes turned on along D-brane worldvolume. Our results, in particular, imply that Abelian worldvolume fluxes can not by themselves stabilize closed string moduli, in a consistent supersymmtric model, for above orientifold compactifications. We also discuss other Z2 orientifolds of T6 and show that certain other brane wrappings are also ruled out by similar consistency requirements. In specific setups we consider examples with D9-branes wrapping on a complex three-torus with its world-volume fluxes taken to be semi-homogeneous bundles and D7-branes wrapping holomorphic four-cycles of the complex three-torus carrying world-volume fluxes.

Bioprinting for cancer research.

PubMed

Knowlton, Stephanie; Onal, Sevgi; Yu, Chu Hsiang; Zhao, Jean J; Tasoglu, Savas

2015-09-01

Bioprinting offers the ability to create highly complex 3D architectures with living cells. This cutting-edge technique has significantly gained popularity and applicability in several fields. Bioprinting methods have been developed to effectively and rapidly pattern living cells, biological macromolecules, and biomaterials. These technologies hold great potential for applications in cancer research. Bioprinted cancer models represent a significant improvement over previous 2D models by mimicking 3D complexity and facilitating physiologically relevant cell-cell and cell-matrix interactions. Here we review bioprinting methods based on inkjet, microextrusion, and laser technologies and compare 3D cancer models with 2D cancer models. We discuss bioprinted models that mimic the tumor microenvironment, providing a platform for deeper understanding of cancer pathology, anticancer drug screening, and cancer treatment development. Copyright © 2015 Elsevier Ltd. All rights reserved.

1D-3D hybrid modeling—from multi-compartment models to full resolution models in space and time

PubMed Central

Grein, Stephan; Stepniewski, Martin; Reiter, Sebastian; Knodel, Markus M.; Queisser, Gillian

2014-01-01

Investigation of cellular and network dynamics in the brain by means of modeling and simulation has evolved into a highly interdisciplinary field, that uses sophisticated modeling and simulation approaches to understand distinct areas of brain function. Depending on the underlying complexity, these models vary in their level of detail, in order to cope with the attached computational cost. Hence for large network simulations, single neurons are typically reduced to time-dependent signal processors, dismissing the spatial aspect of each cell. For single cell or networks with relatively small numbers of neurons, general purpose simulators allow for space and time-dependent simulations of electrical signal processing, based on the cable equation theory. An emerging field in Computational Neuroscience encompasses a new level of detail by incorporating the full three-dimensional morphology of cells and organelles into three-dimensional, space and time-dependent, simulations. While every approach has its advantages and limitations, such as computational cost, integrated and methods-spanning simulation approaches, depending on the network size could establish new ways to investigate the brain. In this paper we present a hybrid simulation approach, that makes use of reduced 1D-models using e.g., the NEURON simulator—which couples to fully resolved models for simulating cellular and sub-cellular dynamics, including the detailed three-dimensional morphology of neurons and organelles. In order to couple 1D- and 3D-simulations, we present a geometry-, membrane potential- and intracellular concentration mapping framework, with which graph- based morphologies, e.g., in the swc- or hoc-format, are mapped to full surface and volume representations of the neuron and computational data from 1D-simulations can be used as boundary conditions for full 3D simulations and vice versa. Thus, established models and data, based on general purpose 1D-simulators, can be directly coupled to the emerging field of fully resolved, highly detailed 3D-modeling approaches. We present the developed general framework for 1D/3D hybrid modeling and apply it to investigate electrically active neurons and their intracellular spatio-temporal calcium dynamics. PMID:25120463

Applications of Black Scholes Complexity Concepts to Combat Modelling

DTIC Science & Technology

2009-03-01

Lauren, G C McIntosh, N D Perry and J Moffat, Chaos 17, 2007. 4 Lanchester Models of Warfare Volumes 1 and 2, J G Taylor, Operations Research Society...transformation matrix A Lanchester Equation solution parameter bi Dependent model variables b(x,t) Variable variance rate B Lanchester Equation solution...distribution. The similarity between this equation and the Lanchester Equations (equation 1) is clear. This suggests an obvious solution to the question of

A Secret 3D Model Sharing Scheme with Reversible Data Hiding Based on Space Subdivision

NASA Astrophysics Data System (ADS)

Tsai, Yuan-Yu

2016-03-01

Secret sharing is a highly relevant research field, and its application to 2D images has been thoroughly studied. However, secret sharing schemes have not kept pace with the advances of 3D models. With the rapid development of 3D multimedia techniques, extending the application of secret sharing schemes to 3D models has become necessary. In this study, an innovative secret 3D model sharing scheme for point geometries based on space subdivision is proposed. Each point in the secret point geometry is first encoded into a series of integer values that fall within [0, p - 1], where p is a predefined prime number. The share values are derived by substituting the specified integer values for all coefficients of the sharing polynomial. The surface reconstruction and the sampling concepts are then integrated to derive a cover model with sufficient model complexity for each participant. Finally, each participant has a separate 3D stego model with embedded share values. Experimental results show that the proposed technique supports reversible data hiding and the share values have higher levels of privacy and improved robustness. This technique is simple and has proven to be a feasible secret 3D model sharing scheme.

Structural complementarity of Toll/interleukin-1 receptor domains in Toll-like receptors and the adaptors Mal and MyD88.

PubMed

Dunne, Aisling; Ejdeback, Mikael; Ludidi, Phumzile L; O'Neill, Luke A J; Gay, Nicholas J

2003-10-17

The Toll/interleukin 1 receptor (TIR) domain is a region found in the cytoplasmic tails of members of the Toll-like receptor/interleukin-1 receptor superfamily. The domain is essential for signaling and is also found in the adaptor proteins Mal (MyD88 adaptor-like) and MyD88, which function to couple activation of the receptor to downstream signaling components. Experimental structures of two Toll/interleukin 1 receptor domains reveal a alpha-beta-fold similar to that of the bacterial chemotaxis protein CheY, and other evidence suggests that the adaptors can make heterotypic interactions with both the receptors and themselves. Here we show that the purified TIR domains of Mal and MyD88 can form stable heterodimers and also that Mal homodimers and oligomers are dissociated in the presence of ATP. To identify structural features that may contribute to the formation of signaling complexes, we produced models of the TIR domains from human Toll-like receptor 4 (TLR4), Mal, and MyD88. We found that although the overall fold is conserved the electrostatic surface potentials are quite distinct. Docking studies of the models suggest that Mal and MyD88 bind to different regions in TLRs 2 and 4, a finding consistent with a cooperative role of the two adaptors in signaling. Mal and MyD88 are predicted to interact at a third non-overlapping site, suggesting that the receptor and adaptors may form heterotetrameric complexes. The theoretical model of the interactions is supported by experimental data from glutathione S-transferase pull-downs and co-immunoprecipitations. Neither theoretical nor experimental data suggest a direct role for the conserved proline in the BB-loop in the association of TLR4, Mal, and MyD88. Finally we show a sequence relationship between the Drosophila protein Tube and Mal that may indicate a functional equivalence of these two adaptors in the Drosophila and vertebrate Toll pathways.

Aggregation of LoD 1 building models as an optimization problem

NASA Astrophysics Data System (ADS)

Guercke, R.; Götzelmann, T.; Brenner, C.; Sester, M.

3D city models offered by digital map providers typically consist of several thousands or even millions of individual buildings. Those buildings are usually generated in an automated fashion from high resolution cadastral and remote sensing data and can be very detailed. However, not in every application such a high degree of detail is desirable. One way to remove complexity is to aggregate individual buildings, simplify the ground plan and assign an appropriate average building height. This task is computationally complex because it includes the combinatorial optimization problem of determining which subset of the original set of buildings should best be aggregated to meet the demands of an application. In this article, we introduce approaches to express different aspects of the aggregation of LoD 1 building models in the form of Mixed Integer Programming (MIP) problems. The advantage of this approach is that for linear (and some quadratic) MIP problems, sophisticated software exists to find exact solutions (global optima) with reasonable effort. We also propose two different heuristic approaches based on the region growing strategy and evaluate their potential for optimization by comparing their performance to a MIP-based approach.

Potent New Small-Molecule Inhibitor of Botulinum Neurotoxin Serotype A Endopeptidase Developed by Synthesis-Based Computer-Aided Molecular Design

DTIC Science & Technology

2009-11-01

dynamics of the complex predicted by multiple molecular dynamics simulations , and discuss further structural optimization to achieve better in vivo efficacy...complex with BoNTAe and the dynamics of the complex predicted by multiple molecular dynamics simulations (MMDSs). On the basis of the 3D model, we discuss...is unlimited whereas AHP exhibited 54% inhibition under the same conditions (Table 1). Computer Simulation Twenty different molecular dynamics

DNA binding by a new metallointercalator that contains a proflavine group bearing a hanging chelating unit.

PubMed

Bazzicalupi, Carla; Bencini, Andrea; Bianchi, Antonio; Biver, Tarita; Boggioni, Alessia; Bonacchi, Sara; Danesi, Andrea; Giorgi, Claudia; Gratteri, Paola; Ingraín, Antonio Marchal; Secco, Fernando; Sissi, Claudia; Valtancoli, Barbara; Venturini, Marcella

2008-01-01

The new bifunctional molecule 3,6-diamine-9-[6,6-bis(2-aminoethyl)-1,6-diaminohexyl]acridine (D), which is characterised by both an aromatic moiety and a separate metal-complexing polyamine centre, has been synthesised. The characteristics of D and its ZnII complex ([ZnD]) (protonation and metal-complexing constants, optical properties and self-aggregation phenomena) have been analysed by means of NMR spectroscopy, potentiometric, spectrophotometric and spectrofluorimetric techniques. The equilibria and kinetics of the binding process of D and [ZnD] to calf thymus DNA have been investigated at I=0.11 M (NaCl) and 298.1 K by using spectroscopic methods and the stopped-flow technique. Static measurements show biphasic behaviour for both D-DNA and [ZnD]-DNA systems; this reveals the occurrence of two different binding processes depending on the polymer-to-dye molar ratio (P/D). The binding mode that occurs at low P/D values is interpreted in terms of external binding with a notable contribution from the polyamine residue. The binding mode at high P/D values corresponds to intercalation of the proflavine residue. Stopped-flow, circular dichroism and supercoiled-DNA unwinding experiments corroborate the proposed mechanism. Molecular-modelling studies support the intercalative process and evidence the influence of NH+...O interactions between the protonated acridine nitrogen atom and the oxygen atoms of the polyanion; these interactions play a key role in determining the conformation of DNA adducts.

Complex Modeling of the Seismic Structure of the Trans-European Suture Zone's Margin from Receiver Function Analysis

NASA Astrophysics Data System (ADS)

Wilde-Piorko, M.; Chrapkiewicz, K.; Lepore, S.; Polkowski, M.; Grad, M.

2016-12-01

The Trans-European Suture Zone (TESZ) is one of the most prominent suture zones in Europe separating the young Paleozoic Platform from the much older Precambrian East European Craton. The data recorded by "13 BB Star" broadband seismic stations (Grad et al., 2015) are analyzed to investigate the crustal and upper mantle structure of the margin of the Trans-European Suture Zone (TESZ) in northern Poland. Receiver function (RF) locally provides the signature of sharp seismic discontinuities and information about the shear wave (S-wave) velocity distribution beneath the seismic station. Recorded seismograms are rotated from ZNE to LQT system with method using the properties of RF (Wilde-Piórko, 2015). Different techniques of receiver function interpretation are applied, including 1-D inversion of RF, 1-D forward modeling of RF, 2.5D forward modeling of RF, 1-D join inversion of RF and dispersion curves of surface wave, to find the best S-wave velocity model of the TESZ margin. A high-resolution 3D P-wave velocity model in the area of Poland (Grad et al. 2016) are used as a starting model. National Science Centre Poland provided financial support for this work by NCN grant DEC-2011/02/A/ST10/00284.

Rule-based modeling and simulations of the inner kinetochore structure.

PubMed

Tschernyschkow, Sergej; Herda, Sabine; Gruenert, Gerd; Döring, Volker; Görlich, Dennis; Hofmeister, Antje; Hoischen, Christian; Dittrich, Peter; Diekmann, Stephan; Ibrahim, Bashar

2013-09-01

Combinatorial complexity is a central problem when modeling biochemical reaction networks, since the association of a few components can give rise to a large variation of protein complexes. Available classical modeling approaches are often insufficient for the analysis of very large and complex networks in detail. Recently, we developed a new rule-based modeling approach that facilitates the analysis of spatial and combinatorially complex problems. Here, we explore for the first time how this approach can be applied to a specific biological system, the human kinetochore, which is a multi-protein complex involving over 100 proteins. Applying our freely available SRSim software to a large data set on kinetochore proteins in human cells, we construct a spatial rule-based simulation model of the human inner kinetochore. The model generates an estimation of the probability distribution of the inner kinetochore 3D architecture and we show how to analyze this distribution using information theory. In our model, the formation of a bridge between CenpA and an H3 containing nucleosome only occurs efficiently for higher protein concentration realized during S-phase but may be not in G1. Above a certain nucleosome distance the protein bridge barely formed pointing towards the importance of chromatin structure for kinetochore complex formation. We define a metric for the distance between structures that allow us to identify structural clusters. Using this modeling technique, we explore different hypothetical chromatin layouts. Applying a rule-based network analysis to the spatial kinetochore complex geometry allowed us to integrate experimental data on kinetochore proteins, suggesting a 3D model of the human inner kinetochore architecture that is governed by a combinatorial algebraic reaction network. This reaction network can serve as bridge between multiple scales of modeling. Our approach can be applied to other systems beyond kinetochores. Copyright © 2013 Elsevier Ltd. All rights reserved.

"Just-In-Time" Simulation Training Using 3-D Printed Cardiac Models After Congenital Cardiac Surgery.

PubMed

Olivieri, Laura J; Su, Lillian; Hynes, Conor F; Krieger, Axel; Alfares, Fahad A; Ramakrishnan, Karthik; Zurakowski, David; Marshall, M Blair; Kim, Peter C W; Jonas, Richard A; Nath, Dilip S

2016-03-01

High-fidelity simulation using patient-specific three-dimensional (3D) models may be effective in facilitating pediatric cardiac intensive care unit (PCICU) provider training for clinical management of congenital cardiac surgery patients. The 3D-printed heart models were rendered from preoperative cross-sectional cardiac imaging for 10 patients undergoing congenital cardiac surgery. Immediately following surgical repair, a congenital cardiac surgeon and an intensive care physician conducted a simulation training session regarding postoperative care utilizing the patient-specific 3D model for the PCICU team. After the simulation, Likert-type 0 to 10 scale questionnaire assessed participant perception of impact of the training session. Seventy clinicians participated in training sessions, including 22 physicians, 38 nurses, and 10 ancillary care providers. Average response to whether 3D models were more helpful than standard hand off was 8.4 of 10. Questions regarding enhancement of understanding and clinical ability received average responses of 9.0 or greater, and 90% of participants scored 8 of 10 or higher. Nurses scored significantly higher than other clinicians on self-reported familiarity with the surgery (7.1 vs. 5.8; P = .04), clinical management ability (8.6 vs. 7.7; P = .02), and ability enhancement (9.5 vs. 8.7; P = .02). Compared to physicians, nurses and ancillary providers were more likely to consider 3D models more helpful than standard hand off (8.7 vs. 7.7; P = .05). Higher case complexity predicted greater enhancement of understanding of surgery (P = .04). The 3D heart models can be used to enhance congenital cardiac critical care via simulation training of multidisciplinary intensive care teams. Benefit may be dependent on provider type and case complexity. © The Author(s) 2016.

"Handling" seismic hazard: 3D printing of California Faults

NASA Astrophysics Data System (ADS)

Kyriakopoulos, C.; Potter, M.; Richards-Dinger, K. B.

2017-12-01

As earth scientists, we face the challenge of how to explain and represent our work and achievements to the general public. Nowadays, this problem is partially alleviated by the use of modern visualization tools such as advanced scientific software (Paraview.org), high resolution monitors, elaborate video simulations, and even 3D Virtual Reality goggles. However, the ability to manipulate and examine a physical object in 3D is still an important tool to connect better with the public. For that reason, we are presenting a scaled 3D printed version of the complex network of earthquake faults active in California based on that used by the Uniform California Earthquake Rupture Forecast 3 (UCERF3) (Field et al., 2013). We start from the fault geometry in the UCERF3.1 deformation model files. These files contain information such as the coordinates of the surface traces of the faults, dip angle, and depth extent. The fault specified in the above files are triangulated at 1km resolution and exported as a facet (.fac) file. The facet file is later imported into the Trelis 15.1 mesh generator (csimsoft.com). We use Trelis to perform the following three operations: First, we scale down the model so that 100 mm corresponds to 100km. Second, we "thicken" the walls of the faults; wall thickness of at least 1mm is necessary in 3D printing. We thicken fault geometry by 1mm on each side of the faults for a total of 2mm thickness. Third, we break down the model into parts that will fit the printing bed size ( 25 x 20mm). Finally, each part is exported in stereolithography format (.stl). For our project, we are using the 3D printing facility within the Creat'R Lab in the UC Riverside Orbach Science Library. The 3D printer is a MakerBot Replicator Desktop, 5th Generation. The resolution of print is 0.2mm (Standard quality). The printing material is the MakerBot PLA Filament, 1.75 mm diameter, large Spool, green. The most complex part of the display model requires approximately 17 hours to print. After assembly, the length of the display is 1.4m. From our initial effort in printing and handling of the 3D printed faults, we conclude that a physical, 3D-printed model is very efficient in eliminating common misconceptions that nonscientists have about earthquake faults, particularly their geometry, extension and orientation in space.

The Impacts of 3-D Earth Structure on GIA-Induced Crustal Deformation and Future Sea-Level Change in the Antarctic

NASA Astrophysics Data System (ADS)

Powell, E. M.; Hay, C.; Latychev, K.; Gomez, N. A.; Mitrovica, J. X.

2016-12-01

Glacial Isostatic Adjustment (GIA) models used to constrain the extent of past ice sheets and viscoelastic Earth structure, or to correct geodetic and geological observables for ice age effects, generally only consider depth-dependent variations in Earth viscosity and lithospheric structure. A et al. [2013] argued that 3-D Earth structure could impact GIA observables in Antarctica, but concluded that the presence of such structure contributes less to GIA uncertainty than do differences in Antarctic deglaciation histories. New seismic and geological evidence, however, indicates the Antarctic is underlain by complex, high amplitude variability in viscoelastic structure, including a low viscosity zone (LVZ) under West Antarctica. Hay et al. [2016] showed that sea-level fingerprints of modern melting calculated using such Earth models differ from those based on elastic or 1-D viscoelastic Earth models within decades of melting. Our investigation is motivated by two questions: (1) How does 3-D Earth structure, especially this LVZ, impact observations of GIA-induced crustal deformation associated with the last deglaciation? (2) How will 3-D Earth structure affect predictions of future sea-level rise in Antarctica? We compute the gravitationally self-consistent sea level, uplift, and gravity changes using the finite volume treatment of Latychev et al. [2005]. We consider four viscoelastic Earth models: a global 1-D model; a regional, West Antarctic-like 1-D model; a 3-D model where the lithospheric thickness varies laterally; and a 3-D model where both viscosity and lithospheric thickness vary laterally. For our Last Glacial Maximum to present investigations we employ ICE6g [Peltier et al., 2015]. For our present-future investigations we consider a melt scenario consistent with GRACE satellite gravity derived solutions [Harig et al., 2015]. Our calculations indicate that predictions of crustal deformations due to both GIA and ongoing melting are strongly influenced by 3-D lithospheric thickness and viscosity structure. Future sea level change due to ongoing melting is primarily influenced by 3-D viscosity structure. We show that 1-D Earth models built using regional inferences of viscosity and lithospheric thickness do not accurately capture the variability introduced by 3-D Earth structure.

The Impacts of 3-D Earth Structure on GIA-Induced Crustal Deformation and Future Sea-Level Change in the Antarctic

NASA Astrophysics Data System (ADS)

Powell, E. M.; Hay, C.; Latychev, K.; Gomez, N. A.; Mitrovica, J. X.

2017-12-01

Glacial Isostatic Adjustment (GIA) models used to constrain the extent of past ice sheets and viscoelastic Earth structure, or to correct geodetic and geological observables for ice age effects, generally only consider depth-dependent variations in Earth viscosity and lithospheric structure. A et al. [2013] argued that 3-D Earth structure could impact GIA observables in Antarctica, but concluded that the presence of such structure contributes less to GIA uncertainty than do differences in Antarctic deglaciation histories. New seismic and geological evidence, however, indicates the Antarctic is underlain by complex, high amplitude variability in viscoelastic structure, including a low viscosity zone (LVZ) under West Antarctica. Hay et al. [2016] showed that sea-level fingerprints of modern melting calculated using such Earth models differ from those based on elastic or 1-D viscoelastic Earth models within decades of melting. Our investigation is motivated by two questions: (1) How does 3-D Earth structure, especially this LVZ, impact observations of GIA-induced crustal deformation associated with the last deglaciation? (2) How will 3-D Earth structure affect predictions of future sea-level rise in Antarctica? We compute the gravitationally self-consistent sea level, uplift, and gravity changes using the finite volume treatment of Latychev et al. [2005]. We consider four viscoelastic Earth models: a global 1-D model; a regional, West Antarctic-like 1-D model; a 3-D model where the lithospheric thickness varies laterally; and a 3-D model where both viscosity and lithospheric thickness vary laterally. For our Last Glacial Maximum to present investigations we employ ICE6g [Peltier et al., 2015]. For our present-future investigations we consider a melt scenario consistent with GRACE satellite gravity derived solutions [Harig et al., 2015]. Our calculations indicate that predictions of crustal deformations due to both GIA and ongoing melting are strongly influenced by 3-D lithospheric thickness and viscosity structure. Future sea level change due to ongoing melting is primarily influenced by 3-D viscosity structure. We show that 1-D Earth models built using regional inferences of viscosity and lithospheric thickness do not accurately capture the variability introduced by 3-D Earth structure.

Clinical application of computer-designed polystyrene models in complex severe spinal deformities: a pilot study

PubMed Central

Mao, Keya; Xiao, Songhua; Liu, Zhengsheng; Zhang, Yonggang; Zhang, Xuesong; Wang, Zheng; Lu, Ning; Shourong, Zhu; Xifeng, Zhang; Geng, Cui; Baowei, Liu

2010-01-01

Surgical treatment of complex severe spinal deformity, involving a scoliosis Cobb angle of more than 90° and kyphosis or vertebral and rib deformity, is challenging. Preoperative two-dimensional images resulting from plain film radiography, computed tomography (CT) and magnetic resonance imaging provide limited morphometric information. Although the three-dimensional (3D) reconstruction CT with special software can view the stereo and rotate the spinal image on the screen, it cannot show the full-scale spine and cannot directly be used on the operation table. This study was conducted to investigate the application of computer-designed polystyrene models in the treatment of complex severe spinal deformity. The study involved 16 cases of complex severe spinal deformity treated in our hospital between 1 May 2004 and 31 December 2007; the mean ± SD preoperative scoliosis Cobb angle was 118° ± 27°. The CT scanning digital imaging and communication in medicine (DICOM) data sets of the affected spinal segments were collected for 3D digital reconstruction and rapid prototyping to prepare computer-designed polystyrene models, which were applied in the treatment of these cases. The computer-designed polystyrene models allowed 3D observation and measurement of the deformities directly, which helped the surgeon to perform morphological assessment and communicate with the patient and colleagues. Furthermore, the models also guided the choice and placement of pedicle screws. Moreover, the models were used to aid in virtual surgery and guide the actual surgical procedure. The mean ± SD postoperative scoliosis Cobb angle was 42° ± 32°, and no serious complications such as spinal cord or major vascular injury occurred. The use of computer-designed polystyrene models could provide more accurate morphometric information and facilitate surgical correction of complex severe spinal deformity. PMID:20213294

Engineering-Aligned 3D Neural Circuit in Microfluidic Device.

PubMed

Bang, Seokyoung; Na, Sangcheol; Jang, Jae Myung; Kim, Jinhyun; Jeon, Noo Li

2016-01-07

The brain is one of the most important and complex organs in the human body. Although various neural network models have been proposed for in vitro 3D neuronal networks, it has been difficult to mimic functional and structural complexity of the in vitro neural circuit. Here, a microfluidic model of a simplified 3D neural circuit is reported. First, the microfluidic device is filled with Matrigel and continuous flow is delivered across the device during gelation. The fluidic flow aligns the extracellular matrix (ECM) components along the flow direction. Following the alignment of ECM fibers, neurites of primary rat cortical neurons are grown into the Matrigel at the average speed of 250 μm d(-1) and form axon bundles approximately 1500 μm in length at 6 days in vitro (DIV). Additionally, neural networks are developed from presynaptic to postsynaptic neurons at 14 DIV. The establishment of aligned 3D neural circuits is confirmed with the immunostaining of PSD-95 and synaptophysin and the observation of calcium signal transmission. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modeling of the contrast-enhanced perfusion test in liver based on the multi-compartment flow in porous media.

PubMed

Rohan, Eduard; Lukeš, Vladimír; Jonášová, Alena

2018-01-24

The paper deals with modeling the liver perfusion intended to improve quantitative analysis of the tissue scans provided by the contrast-enhanced computed tomography (CT). For this purpose, we developed a model of dynamic transport of the contrast fluid through the hierarchies of the perfusion trees. Conceptually, computed time-space distributions of the so-called tissue density can be compared with the measured data obtained from CT; such a modeling feedback can be used for model parameter identification. The blood flow is characterized at several scales for which different models are used. Flows in upper hierarchies represented by larger branching vessels are described using simple 1D models based on the Bernoulli equation extended by correction terms to respect the local pressure losses. To describe flows in smaller vessels and in the tissue parenchyma, we propose a 3D continuum model of porous medium defined in terms of hierarchically matched compartments characterized by hydraulic permeabilities. The 1D models corresponding to the portal and hepatic veins are coupled with the 3D model through point sources, or sinks. The contrast fluid saturation is governed by transport equations adapted for the 1D and 3D flow models. The complex perfusion model has been implemented using the finite element and finite volume methods. We report numerical examples computed for anatomically relevant geometries of the liver organ and of the principal vascular trees. The simulated tissue density corresponding to the CT examination output reflects a pathology modeled as a localized permeability deficiency.

The Complex Outgassing of Comets and the Resulting Coma, a Direct Simulation Monte-Carlo Approach

NASA Astrophysics Data System (ADS)

Fougere, Nicolas

During its journey, when a comet gets within a few astronomical units of the Sun, solar heating liberates gases and dust from its icy nucleus forming a rarefied cometary atmosphere, the so-called coma. This tenuous atmosphere can expand to distances up to millions of kilometers representing orders of magnitude larger than the nucleus size. Most of the practical cases of coma studies involve the consideration of rarefied gas flows under non-LTE conditions where the hydrodynamics approach is not valid. Then, the use of kinetic methods is required to properly study the physics of the cometary coma. The Direct Simulation Monte-Carlo (DSMC) method is the method of choice to solve the Boltzmann equation, giving the opportunity to study the cometary atmosphere from the inner coma where collisions dominate and is in thermodynamic equilibrium to the outer coma where densities are lower and free flow conditions are verified. While previous studies of the coma used direct sublimation from the nucleus for spherically symmetric 1D models, or 2D models with a day/night asymmetry, recent observations of comets showed the existence of local small source areas such as jets, and extended sources via sublimating icy grains, that must be included into cometary models for a realistic representation of the physics of the coma. In this work, we present, for the first time, 1D, 2D, and 3D models that can take into account the full effects of conditions with more complex sources of gas with jets and/or icy grains. Moreover, an innovative work in a full 3D description of the cometary coma using a kinetic method with a realistic nucleus and outgassing is demonstrated. While most of the physical models used in this study had already been developed, they are included in one self-consistent coma model for the first time. The inclusion of complex cometary outgassing processes represents the state-of-the-art of cometary coma modeling. This provides invaluable information about the coma by refining the understanding of the material that constitutes comets. This helps us to comprehend the process of the Solar System formation, one of the top priority questions in the 2013-2022 Planetary Science Decadal survey.

Patterned corneal collagen crosslinking for astigmatism: Computational modeling study

PubMed Central

Seven, Ibrahim; Roy, Abhijit Sinha; Dupps, William J.

2014-01-01

PURPOSE To test the hypothesis that spatially selective corneal stromal stiffening can alter corneal astigmatism and assess the effects of treatment orientation, pattern, and material model complexity in computational models using patient-specific geometries. SETTING Cornea and Refractive Surgery Service, Academic Eye Institute, Cleveland, Ohio, USA. DESIGN Computational modeling study. METHODS Three-dimensional corneal geometries from 10 patients with corneal astigmatism were exported from a clinical tomography system (Pentacam). Corneoscleral finite element models of each eye were generated. Four candidate treatment patterns were simulated, and the effects of treatment orientation and magnitude of stiffening on anterior curvature and aberrations were studied. The effect of material model complexity on simulated outcomes was also assessed. RESULTS Pretreatment anterior corneal astigmatism ranged from 1.22 to 3.92 diopters (D) in a series that included regular and irregular astigmatic patterns. All simulated treatment patterns oriented on the flat axis resulted in mean reductions in corneal astigmatism and depended on the pattern geometry. The linear bow-tie pattern produced a greater mean reduction in astigmatism (1.08 D ± 0.13 [SD]; range 0.74 to 1.23 D) than other patterns tested under an assumed 2-times increase in corneal stiffness, and it had a nonlinear relationship to the degree of stiffening. The mean astigmatic effect did not change significantly with a fiber- or depth-dependent model, but it did affect the coupling ratio. CONCLUSIONS In silico simulations based on patient-specific geometries suggest that clinically significant reductions in astigmatism are possible with patterned collagen crosslinking. Effect magnitude was dependent on patient-specific geometry, effective stiffening pattern, and treatment orientation. PMID:24767795

Electrostatic Rate Enhancement and Transient Complex of Protein-Protein Association

PubMed Central

Alsallaq, Ramzi; Zhou, Huan-Xiang

2012-01-01

The association of two proteins is bounded by the rate at which they, via diffusion, find each other while in appropriate relative orientations. Orientational constraints restrict this rate to ~105 – 106 M−1s−1. Proteins with higher association rates generally have complementary electrostatic surfaces; proteins with lower association rates generally are slowed down by conformational changes upon complex formation. Previous studies (Zhou, Biophys. J. 1997;73:2441–2445) have shown that electrostatic enhancement of the diffusion-limited association rate can be accurately modeled by kD = kD0 exp(−*/ kBT), where kD and kD0 are the rates in the presence and absence of electrostatic interactions, respectively, * is the average electrostatic interaction energy in a “transient-complex” ensemble, and kBT is thermal energy. The transient-complex ensemble separates the bound state from the unbound state. Predictions of the transient-complex theory on four protein complexes were found to agree well with experiment when the electrostatic interaction energy was calculated with the linearized Poisson-Boltzmann (PB) equation (Alsallaq and Zhou, Structure 2007, 15:215–224). Here we show that the agreement is further improved when the nonlinear PB equation is used. These predictions are obtained with the dielectric boundary defined as the protein van der Waals surface. When the dielectric boundary is instead specified as the molecular surface, electrostatic interactions in the transient complex become repulsive and are thus predicted to retard association. Together these results demonstrate that the transient-complex theory is predictive of electrostatic rate enhancement and can help parameterize PB calculations. PMID:17932929

Effect of three bis-pyridyl-bis-amide ligands with various spacers on the structural diversity of new multifunctional cobalt(II) coordination polymers

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

Lin, Hong-Yan; Lu, Huizhe; Le, Mao

2015-03-15

Three new cobalt(II) coordination polymers [Co{sub 2}(1,4-NDC){sub 2}(3-bpye)(H{sub 2}O)] (1), [Co(1,4-NDC)(3-bpfp)(H{sub 2}O)] (2) and [Co(1,4-NDC)(3-bpcb)] (3) [3-bpye=N,N′-bis(3-pyridinecarboxamide)-1,2-ethane, 3-bpfp=bis(3-pyridylformyl)piperazine, 3-bpcb=N,N′-bis(3-pyridinecarboxamide)-1,4-benzene, and 1,4-H{sub 2}NDC=1,4-naphthalenedicarboxylic acid] have been hydrothermally synthesized. The structures of complexes 1–3 have been determined by X-ray single crystal diffraction analyses and further characterized by infrared spectroscopy (IR), powder X-ray diffraction (PXRD) and thermogravimetric analyses (TGA). Complex 1 is a 3D coordination structure with 8-connected (4{sup 20}.6{sup 8}) topology constructed from 3D [Co{sub 2}(1,4-NDC){sub 2}(H{sub 2}O)]{sub n} framework and bidentate 3-bpye ligands. Complex 2 shows 1D “cage+cage”-like chain formed by 1D [Co{sub 2}(1,4-NDC){sub 2}]{sub n} ribbon chains and [Co{sub 2}(3-bpfp){submore » 2}] loops, which are further linked by hydrogen bonding interactions to form a 3D supramolecular network. Complex 3 displays a 3D coordination network with a 6-connected (4{sup 12}.6{sup 3}) topology based on 2D [Co{sub 2}(1,4-NDC){sub 2}]{sub n} layers and bidentate 3-bpcb bridging ligands. The influences of different bis-pyridyl-bis-amide ligands with various spacers on the structures of title complexes are studied. Moreover, the fluorescent properties, electrochemical behaviors and magnetic properties of complexes 1–3 have been investigated. - Graphical abstract: Three multifunctional cobalt(II) complexes constructed from three bis-pyridyl-bis-amide and 1,4-naphthalenedicarboxylic acid have been hydrothermally synthesized and characterized. The fluorescent, electrochemical and magnetic properties of 1–3 have been investigated. - Highlights: • Three multifunctional cobalt(II) complexes based on various bis-pyridyl-bis-amide ligands. • Complex 1 is a 3D coordination structure with 8-connected (4{sup 20}.6{sup 8}) topology. • Complex 2 is a 1D “cage+cage”-like chain. • Complex 3 is a 3D coordination network with a 6-connected (4{sup 12}.6{sup 3}) topology. • The fluorescent, electrochemical and magnetic properties of 1–3 were reported.« less

Biomechanics of compensatory mechanisms in spinal-pelvic complex

NASA Astrophysics Data System (ADS)

Ivanov, D. V.; Hominets, V. V.; Kirillova, I. V.; Kossovich, L. Yu; Kudyashev, A. L.; Teremshonok, A. V.

2018-04-01

3D geometric solid computer model of spinal-pelvic complex was constructed on the basis of computed tomography and full body X-ray in standing position data. The constructed model was used for biomechanical analysis of compensatory mechanisms arising in the spine with anteversion and retroversion of the pelvis. The results of numerical biomechanical 3D modeling are in good agreement with the clinical data.

Resolvin D1 and D2 Reverse Lipopolysaccharide-Induced Depression-Like Behaviors Through the mTORC1 Signaling Pathway.

PubMed

Deyama, Satoshi; Ishikawa, Yuka; Yoshikawa, Kotomi; Shimoda, Kento; Ide, Soichiro; Satoh, Masamichi; Minami, Masabumi

2017-07-01

Resolvin D1 and D2 are bioactive lipid mediators that are generated from docosahexaenoic acid. Although recent preclinical studies suggest that these compounds have antidepressant effects, their mechanisms of action remain unclear. We investigated mechanisms underlying the antidepressant effects of resolvin D1 and resolvin D2 in lipopolysaccharide (0.8 mg/kg, i.p.)-induced depression model mice using a tail suspension test. I.c.v. infusion of resolvin D1 (10 ng) and resolvin D2 (10 ng) produced antidepressant effects; these effects were significantly blocked by a resolvin D1 receptor antagonist WRW4 (10 µg, i.c.v.) and a resolvin D2 receptor antagonist O-1918 (10 µg, i.c.v.), respectively. The mammalian target of rapamycin complex 1 inhibitor rapamycin (10 mg/kg, i.p.) and a mitogen-activated protein kinase kinase inhibitor U0126 (5 µg, i.c.v.) significantly blocked the antidepressant effects of resolvin D1 and resolvin D2. An AMPA receptor antagonist NBQX (10 mg/kg, i.p.) and a phosphoinositide 3-kinase inhibitor LY294002 (3 µg, i.c.v.) blocked the antidepressant effects of resolvin D1 significantly, but not of resolvin D2. Bilateral infusions of resolvin D1 (0.3 ng/side) or resolvin D2 (0.3 ng/side) into the medial prefrontal cortex or dentate gyrus of the hippocampus produced antidepressant effects. These findings demonstrate that resolvin D1 and resolvin D2 produce antidepressant effects via the mammalian target of rapamycin complex 1 signaling pathway, and that the medial prefrontal cortex and dentate gyrus are important brain regions for these antidepressant effects. These compounds and their receptors may be promising targets for the development of novel rapid-acting antidepressants, like ketamine and scopolamine. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Analysis of Nidogen-1/Laminin γ1 Interaction by Cross-Linking, Mass Spectrometry, and Computational Modeling Reveals Multiple Binding Modes

PubMed Central

Lössl, Philip; Kölbel, Knut; Tänzler, Dirk; Nannemann, David; Ihling, Christian H.; Keller, Manuel V.; Schneider, Marian; Zaucke, Frank; Meiler, Jens; Sinz, Andrea

2014-01-01

We describe the detailed structural investigation of nidogen-1/laminin γ1 complexes using full-length nidogen-1 and a number of laminin γ1 variants. The interactions of nidogen-1 with laminin variants γ1 LEb2–4, γ1 LEb2–4 N836D, γ1 short arm, and γ1 short arm N836D were investigated by applying a combination of (photo-)chemical cross-linking, high-resolution mass spectrometry, and computational modeling. In addition, surface plasmon resonance and ELISA studies were used to determine kinetic constants of the nidogen-1/laminin γ1 interaction. Two complementary cross-linking strategies were pursued to analyze solution structures of laminin γ1 variants and nidogen-1. The majority of distance information was obtained with the homobifunctional amine-reactive cross-linker bis(sulfosuccinimidyl)glutarate. In a second approach, UV-induced cross-linking was performed after incorporation of the diazirine-containing unnatural amino acids photo-leucine and photo-methionine into laminin γ1 LEb2–4, laminin γ1 short arm, and nidogen-1. Our results indicate that Asn-836 within laminin γ1 LEb3 domain is not essential for complex formation. Cross-links between laminin γ1 short arm and nidogen-1 were found in all protein regions, evidencing several additional contact regions apart from the known interaction site. Computational modeling based on the cross-linking constraints indicates the existence of a conformational ensemble of both the individual proteins and the nidogen-1/laminin γ1 complex. This finding implies different modes of interaction resulting in several distinct protein-protein interfaces. PMID:25387007

Modeling and simulation of ocean wave propagation using lattice Boltzmann method

NASA Astrophysics Data System (ADS)

Nuraiman, Dian

2017-10-01

In this paper, we present on modeling and simulation of ocean wave propagation from the deep sea to the shoreline. This requires high computational cost for simulation with large domain. We propose to couple a 1D shallow water equations (SWE) model with a 2D incompressible Navier-Stokes equations (NSE) model in order to reduce the computational cost. The coupled model is solved using the lattice Boltzmann method (LBM) with the lattice Bhatnagar-Gross-Krook (BGK) scheme. Additionally, a special method is implemented to treat the complex behavior of free surface close to the shoreline. The result shows the coupled model can reduce computational cost significantly compared to the full NSE model.

A new supramolecular chromium(III) complex: Synthesis, structural determination, optical study, magnetic and antibacterial activity

NASA Astrophysics Data System (ADS)

Dridi, Rihab; Dhieb, Cyrine; Cherni, Saoussen Namouchi; Boudjada, Nassira Chniba; Sadfi Zouaoui, Najla; Zid, Mohamed Faouzi

2018-01-01

A new chromium (III) complex 1,5-Naphthyridine Trans-diaquadioxalatochromate (III) dihydrate, had been synthesized by self-assembly of chromium (III) nitrate with oxalic acid and 1,5-Naphthyridine. The complex was characterized by X-ray diffraction, Fourier Transform Infrared spectroscopy, thermogravimetric analysis and UV-Visible spectroscopy. The crystal morphology was carried out using Bravais-Friedel-Donnay-Harker (BFDH) model. Single crystal X-Ray structure determination revealed that the complex posses two crystallographically independent Cr(III) centers. Each Cr(III) has a distorted octahedron geometry involving two axial O atoms from two water molecules and four equatorial O atoms from two oxalate dianions forming trans-[Cr(C2O4)2(H2O)2]- complex anions. The charge compensation is accomplished by the incorporation of 1,5-Naphthyridine cations. Connection between these entities is ensured by means of strong hydrogen bonds giving rise to 3D supramolecular architecture. Hirshfeld surface analysis and the related 2D fingerprint plots were used for decoding plausible intermolecular interactions in the crystal packing. The magnetic properties of the complex had been investigated and discussed in the context of its structure. The antimicrobial activity was evaluated by disc diffusion method highlighting an antagonistic effect of the synthesized complex against Gram-positive and Gram-negative species.

From Neural and Social Cooperation to the Global Emergence of Cognition

PubMed Central

Grigolini, Paolo; Piccinini, Nicola; Svenkeson, Adam; Pramukkul, Pensri; Lambert, David; West, Bruce J.

2015-01-01

The recent article (Turalska et al., 2012) discusses the emergence of intelligence via criticality as a consequence of locality breakdown. Herein, we use criticality for the foundation of a novel generation of game theory making the local interaction between players yield long-range effects. We first establish that criticality is not confined to the Ising-like structure of the sociological model of (Turalska et al., 2012), called the decision making model (DMM), through the study of the emergence of altruism using the altruism-selfishness model (ASM). Both models generate criticality, one by imitation of opinion (DMM) and the other by imitation of behavior (ASM). The dynamics of a sociological network 𝒮 influences the behavioral network ℱ through two game theoretic paradigms: (i) the value of altruism; (ii) the benefit of rapid consensus. In (i), the network 𝒮 debates the moral issue of altruism by means of the DMM, while at the level ℱ the individuals operate according to the ASM. The individuals of the level 𝒮, through a weak influence on the individuals of the level ℱ, exert a societal control on ℱ, fitting the principle of complexity management and complexity matching. In (ii), the benefit to society is the rapid attainment of consensus in the 𝒮 level. The agents of the level ℱ operate according to the prisoner’s dilemma prescription, with the defectors acting as DMM contrarians at the level 𝒮. The contrarians, acting as the inhibitory links of neural networks, exert on society the same beneficial effect of maintaining the criticality-induced resilience that they generate in neural networks. The conflict between personal and social benefit makes the networks evolve toward criticality. Finally, we show that the theory of this article is compatible with recent discoveries in the burgeoning field of social neuroscience. PMID:26137455

The Implications of 3D Thermal Structure on 1D Atmospheric Retrieval

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

Blecic, Jasmina; Dobbs-Dixon, Ian; Greene, Thomas, E-mail: jasmina@nyu.edu

Using the atmospheric structure from a 3D global radiation-hydrodynamic simulation of HD 189733b and the open-source Bayesian Atmospheric Radiative Transfer (BART) code, we investigate the difference between the secondary-eclipse temperature structure produced with a 3D simulation and the best-fit 1D retrieved model. Synthetic data are generated by integrating the 3D models over the Spitzer , the Hubble Space Telescope ( HST ), and the James Web Space Telescope ( JWST ) bandpasses, covering the wavelength range between 1 and 11 μ m where most spectroscopically active species have pronounced features. Using the data from different observing instruments, we present detailedmore » comparisons between the temperature–pressure profiles recovered by BART and those from the 3D simulations. We calculate several averages of the 3D thermal structure and explore which particular thermal profile matches the retrieved temperature structure. We implement two temperature parameterizations that are commonly used in retrieval to investigate different thermal profile shapes. To assess which part of the thermal structure is best constrained by the data, we generate contribution functions for our theoretical model and each of our retrieved models. Our conclusions are strongly affected by the spectral resolution of the instruments included, their wavelength coverage, and the number of data points combined. We also see some limitations in each of the temperature parametrizations, as they are not able to fully match the complex curvatures that are usually produced in hydrodynamic simulations. The results show that our 1D retrieval is recovering a temperature and pressure profile that most closely matches the arithmetic average of the 3D thermal structure. When we use a higher resolution, more data points, and a parametrized temperature profile that allows more flexibility in the middle part of the atmosphere, we find a better match between the retrieved temperature and pressure profile and the arithmetic average. The Spitzer and HST simulated observations sample deep parts of the planetary atmosphere and provide fewer constraints on the temperature and pressure profile, while the JWST observations sample the middle part of the atmosphere, providing a good match with the middle and most complex part of the arithmetic average of the 3D temperature structure.« less

Review of Zero-D and 1-D Models of Blood Flow in the Cardiovascular System

PubMed Central

2011-01-01

Background Zero-dimensional (lumped parameter) and one dimensional models, based on simplified representations of the components of the cardiovascular system, can contribute strongly to our understanding of circulatory physiology. Zero-D models provide a concise way to evaluate the haemodynamic interactions among the cardiovascular organs, whilst one-D (distributed parameter) models add the facility to represent efficiently the effects of pulse wave transmission in the arterial network at greatly reduced computational expense compared to higher dimensional computational fluid dynamics studies. There is extensive literature on both types of models. Method and Results The purpose of this review article is to summarise published 0D and 1D models of the cardiovascular system, to explore their limitations and range of application, and to provide an indication of the physiological phenomena that can be included in these representations. The review on 0D models collects together in one place a description of the range of models that have been used to describe the various characteristics of cardiovascular response, together with the factors that influence it. Such models generally feature the major components of the system, such as the heart, the heart valves and the vasculature. The models are categorised in terms of the features of the system that they are able to represent, their complexity and range of application: representations of effects including pressure-dependent vessel properties, interaction between the heart chambers, neuro-regulation and auto-regulation are explored. The examination on 1D models covers various methods for the assembly, discretisation and solution of the governing equations, in conjunction with a report of the definition and treatment of boundary conditions. Increasingly, 0D and 1D models are used in multi-scale models, in which their primary role is to provide boundary conditions for sophisticate, and often patient-specific, 2D and 3D models, and this application is also addressed. As an example of 0D cardiovascular modelling, a small selection of simple models have been represented in the CellML mark-up language and uploaded to the CellML model repository http://models.cellml.org/. They are freely available to the research and education communities. Conclusion Each published cardiovascular model has merit for particular applications. This review categorises 0D and 1D models, highlights their advantages and disadvantages, and thus provides guidance on the selection of models to assist various cardiovascular modelling studies. It also identifies directions for further development, as well as current challenges in the wider use of these models including service to represent boundary conditions for local 3D models and translation to clinical application. PMID:21521508

3D reconstruction modeling of bulk heterojunction organic photovoltaic cells: Effect of the complexity of the boundary on the morphology

NASA Astrophysics Data System (ADS)

Kim, Sung-Jin; Jeong, Daun; Kim, SeongMin; Choi, Yeong Suk; Ihn, Soo-Ghang; Yun, Sungyoung; Lim, Younhee; Lee, Eunha; Park, Gyeong-Su

2016-02-01

Although the morphology of the active layer in bulk heterojunction organic photovoltaic (BHJ-OPV) cells is critical for determining the quantum efficiency (QE), predicting the real QE for a 3-dimensional (3D) morphology has long been difficult because structural information on the composition complexity of donor (D): acceptor (A) blends with small domain size is limited to 2D observations via various image-processing techniques. To overcome this, we reconstruct the 3D morphology by using an isotropic statistical approach based on 2D energy-filtered transmission electron microscopy (EF-TEM) images. This new reconstruction method is validated to obtain the internal QE by using a dynamic Monte Carlo simulation in the BHJ-OPV system with different additives such as 4 vol% 1-chloronaphthalene (CN) and 4 vol% 1,8-diiodooctane (DIO) (compared to the case of no additive); the resulting trend is compared with the experimental QE. Therefore, our developed method can be used to predict the real charge transport performance in the OPV system accurately.

Lift-Off: Using Reference Imagery and Freehand Sketching to Create 3D Models in VR.

PubMed

Jackson, Bret; Keefe, Daniel F

2016-04-01

Three-dimensional modeling has long been regarded as an ideal application for virtual reality (VR), but current VR-based 3D modeling tools suffer from two problems that limit creativity and applicability: (1) the lack of control for freehand modeling, and (2) the difficulty of starting from scratch. To address these challenges, we present Lift-Off, an immersive 3D interface for creating complex models with a controlled, handcrafted style. Artists start outside of VR with 2D sketches, which are then imported and positioned in VR. Then, using a VR interface built on top of image processing algorithms, 2D curves within the sketches are selected interactively and "lifted" into space to create a 3D scaffolding for the model. Finally, artists sweep surfaces along these curves to create 3D models. Evaluations are presented for both long-term users and for novices who each created a 3D sailboat model from the same starting sketch. Qualitative results are positive, with the visual style of the resulting models of animals and other organic subjects as well as architectural models matching what is possible with traditional fine art media. In addition, quantitative data from logging features built into the software are used to characterize typical tool use and suggest areas for further refinement of the interface.

Multiple templates-based homology modeling enhances structure quality of AT1 receptor: validation by molecular dynamics and antagonist docking.

PubMed

Sokkar, Pandian; Mohandass, Shylajanaciyar; Ramachandran, Murugesan

2011-07-01

We present a comparative account on 3D-structures of human type-1 receptor (AT1) for angiotensin II (AngII), modeled using three different methodologies. AngII activates a wide spectrum of signaling responses via the AT1 receptor that mediates physiological control of blood pressure and diverse pathological actions in cardiovascular, renal, and other cell types. Availability of 3D-model of AT1 receptor would significantly enhance the development of new drugs for cardiovascular diseases. However, templates of AT1 receptor with low sequence similarity increase the complexity in straightforward homology modeling, and hence there is a need to evaluate different modeling methodologies in order to use the models for sensitive applications such as rational drug design. Three models were generated for AT1 receptor by, (1) homology modeling with bovine rhodopsin as template, (2) homology modeling with multiple templates and (3) threading using I-TASSER web server. Molecular dynamics (MD) simulation (15 ns) of models in explicit membrane-water system, Ramachandran plot analysis and molecular docking with antagonists led to the conclusion that multiple template-based homology modeling outweighs other methodologies for AT1 modeling.

Electrostatic rate enhancement and transient complex of protein-protein association.

PubMed

Alsallaq, Ramzi; Zhou, Huan-Xiang

2008-04-01

The association of two proteins is bounded by the rate at which they, via diffusion, find each other while in appropriate relative orientations. Orientational constraints restrict this rate to approximately 10(5)-10(6) M(-1) s(-1). Proteins with higher association rates generally have complementary electrostatic surfaces; proteins with lower association rates generally are slowed down by conformational changes upon complex formation. Previous studies (Zhou, Biophys J 1997;73:2441-2445) have shown that electrostatic enhancement of the diffusion-limited association rate can be accurately modeled by $k_{\\bf D}$ = $k_{D}0\\ {exp} ( - \\langle U_{el} \\rangle;{\\star}/k_{B} T),$ where k(D) and k(D0) are the rates in the presence and absence of electrostatic interactions, respectively, U(el) is the average electrostatic interaction energy in a "transient-complex" ensemble, and k(B)T is the thermal energy. The transient-complex ensemble separates the bound state from the unbound state. Predictions of the transient-complex theory on four protein complexes were found to agree well with the experiment when the electrostatic interaction energy was calculated with the linearized Poisson-Boltzmann (PB) equation (Alsallaq and Zhou, Structure 2007;15:215-224). Here we show that the agreement is further improved when the nonlinear PB equation is used. These predictions are obtained with the dielectric boundary defined as the protein van der Waals surface. When the dielectric boundary is instead specified as the molecular surface, electrostatic interactions in the transient complex become repulsive and are thus predicted to retard association. Together these results demonstrate that the transient-complex theory is predictive of electrostatic rate enhancement and can help parameterize PB calculations. (c) 2007 Wiley-Liss, Inc.

The PAC-MAN model: Benchmark case for linear acoustics in computational physics

NASA Astrophysics Data System (ADS)

Ziegelwanger, Harald; Reiter, Paul

2017-10-01

Benchmark cases in the field of computational physics, on the one hand, have to contain a certain complexity to test numerical edge cases and, on the other hand, require the existence of an analytical solution, because an analytical solution allows the exact quantification of the accuracy of a numerical simulation method. This dilemma causes a need for analytical sound field formulations of complex acoustic problems. A well known example for such a benchmark case for harmonic linear acoustics is the ;Cat's Eye model;, which describes the three-dimensional sound field radiated from a sphere with a missing octant analytically. In this paper, a benchmark case for two-dimensional (2D) harmonic linear acoustic problems, viz., the ;PAC-MAN model;, is proposed. The PAC-MAN model describes the radiated and scattered sound field around an infinitely long cylinder with a cut out sector of variable angular width. While the analytical calculation of the 2D sound field allows different angular cut-out widths and arbitrarily positioned line sources, the computational cost associated with the solution of this problem is similar to a 1D problem because of a modal formulation of the sound field in the PAC-MAN model.

3D Printing to Model Surgical Repair of Complex Congenitally Corrected Transposition of the Great Arteries.

PubMed

Sahayaraj, R Anto; Ramanan, Sowmya; Subramanyan, Raghavan; Cherian, Kotturathu Mammen

2017-01-01

We report the use of three-dimensional (3D) modeling to plan surgery for physiologic repair of congenitally corrected transposition of the great arteries with pulmonary atresia, dextrocardia, and complex intra cardiac anatomy. Based on measurements made from the 3D printed model of the actual patient's anatomy, we anticipated using a composite valved conduit (Dacron tube graft, decellularized bovine jugular vein, and aortic homograft) to establish left ventricle-to-pulmonary artery continuity with relief of stenosis involving the pulmonary artery confluence and bilateral branch pulmonary arteries.

New Micro- and Macroscopic Models of Contact and Friction

DTIC Science & Technology

1993-11-29

prima Iriy lv d ito the complex structure of engineering surfaces., the severe clas;t o -p1lastic del,’fulormto.Ia un heat generation, atomnic...reflect an urg-ent need for constructing new coitst~itIt ive iaoh’lls of contact mci’ frictiott alid for estimating, the necessary materia ~l...frictionald initerlace miodels. Thes:e aire: 1. phenormenological models based prima ~rily onl experlnirioidtta observtlions-, a id~ 2. asperity- based models

Tetranuclear copper(II) complexes bridged by alpha-D-glucose-1-phosphate and incorporation of sugar acids through the Cu4 core structural changes.

PubMed

Kato, Merii; Sah, Ajay Kumar; Tanase, Tomoaki; Mikuriya, Masahiro

2006-08-21

Tetranuclear copper(II) complexes containing alpha-D-glucose-1-phosphate (alpha-D-Glc-1P), [Cu4(mu-OH){mu-(alpha-D-Glc-1P)}2(bpy)4(H2O)2]X3 [X = NO3 (1a), Cl (1b), Br (1c)], and [Cu4(mu-OH){mu-(alpha-D-Glc-1P)}2(phen)4(H2O)2](NO3)3 (2) were prepared by reacting the copper(II) salt with Na2[alpha-D-Glc-1P] in the presence of diimine ancillary ligands, and the structure of 2 was characterized by X-ray crystallography to comprise four {Cu(phen)}2+ fragments connected by the two sugar phosphate dianions in 1,3-O,O' and 1,1-O mu4-bridging fashion as well as a mu-hydroxo anion. The crystal structure of 2 involves two chemically independent complex cations in which the C2 enantiomeric structure for the trapezoidal tetracopper(II) framework is switched according to the orientation of the alpha-D-glucopyranosyl moieties. Temperature-dependent magnetic susceptibility data of 1a indicated that antiferromagnetic spin coupling is operative between the two metal ions joined by the hydroxo bridge (J = -52 cm(-1)) while antiferromagnetic interaction through the Cu-O-Cu sugar phosphate bridges is weak (J = -13 cm(-1)). Complex 1a readily reacted with carboxylic acids to afford the tetranuclear copper(II) complexes, [Cu4{mu-(alpha-D-Glc-1P)}2(mu-CA)2(bpy)4](NO3)2 [CA = CH3COO (3), o-C6H4(COO)(COOH) (4)]. Reactions with m-phenylenediacetic acid [m-C6H4(CH2COOH)2] also gave the discrete tetracopper(II) cationic complex [Cu4{mu-(alpha-D-Glc-1P)}2(mu-m-C6H4(CH2COO)(CH2COOH))2(bpy)4](NO3)2 (5a) as well as the cluster polymer formulated as {[Cu4{mu-(alpha-D-Glc-1P)}2(mu-m-C6H4(CH2COO)2)(bpy)4](NO3)2}n (5b). The tetracopper structure of 1a is converted into a symmetrical rectangular core in complexes 3, 4, and 5b, where the hydroxo bridge is dissociated and, instead, two carboxylate anions bridge another pair of Cu(II) ions in a 1,1-O monodentate fashion. The similar reactions were applied to incorporate sugar acids onto the tetranuclear copper(II) centers. Reactions of 1a with delta-D-gluconolactone, D-glucuronic acid, or D-glucaric acid in dimethylformamide resulted in the formation of discrete tetracopper complexes with sugar acids, [Cu4{mu-(alpha-D-Glc-1P)}2(mu-SA)2(bpy)4](NO3)2 [SA = D-gluconate (6), D-glucuronate (7), D-glucarateH (8a)]. The structures of 6 and 7 were determined by X-ray crystallography to be almost identical with that of 3 with additional chelating coordination of the C-2 hydroxyl group of D-gluconate moieties (6) or the C-5 cyclic O atom of D-glucuronate units (7). Those with D-glucaric acid and D-lactobionic acid afforded chiral one-dimensional polymers, {[Cu4{mu-(alpha-D-Glc-1P)}2(mu-D-glucarate)(bpy)4](NO3)2}n (8b) and {[Cu4{mu-(alpha-D-Glc-1P)}2(mu-D-lactobionate)(bpy)4(H2O)2](NO3)3}n (9), respectively, in which the D-Glc-1P-bridged tetracopper(II) units are connected by sugar acid moieties through the C-1 and C-6 carboxylate O atoms in 8b and the C-1 carboxylate and C-6 alkoxy O atoms of the gluconate chain in 9. When complex 7 containing d-glucuronate moieties was heated in water, the mononuclear copper(II) complex with 2-dihydroxy malonate, [Cu(mu-O2CC(OH)2CO2)(bpy)] (10), and the dicopper(II) complex with oxalate, [Cu2(mu-C2O4)(bpy)2(H2O)2](NO3)2 (11), were obtained as a result of oxidative degradation of the carbohydrates through C-C bond cleavage reactions.

Contribution of Electrostatics to the Kinetics of Electron Transfer from NADH-Cytochrome b5 Reductase to Fe(III)-Cytochrome b5.

PubMed

Kollipara, Sireesha; Tatireddy, Shivakishore; Pathirathne, Thusitha; Rathnayake, Lasantha K; Northrup, Scott H

2016-08-25

Brownian dynamics (BD) simulations provide here a theoretical atomic-level treatment of the reduction of human ferric cytochrome b5 (cyt b5) by NADH-cytochrome b5 reductaste (cyt b5r) and several of its mutants. BD is used to calculate the second-order rate constant of electron transfer (ET) between the proteins for direct correlation with experiments. Interestingly, the inclusion of electrostatic forces dramatically increases the reaction rate of the native proteins despite the overall negative charge of both proteins. The role played by electrostatic charge distribution in stabilizing the ET complexes and the role of mutations of several amino acid residues in stabilizing or destabilizing the complexes are analyzed. The complex with the shortest ET reaction distance (d = 6.58 Å) from rigid body BD is further subjected to 1 ns of molecular dynamics (MD) in a periodic box of TIP3P water to produce a more stable complex allowed by flexibility and with a shorter average reaction distance d = 6.02 Å. We predict a docking model in which the following ion-ion interactions are dominant (cyt b5r/cyt b5): Lys162-Heme O1D/Lys163-Asp64/Arg91-Heme O1A/Lys125-Asp70.

simplified aerosol representations in global modeling

NASA Astrophysics Data System (ADS)

Kinne, Stefan; Peters, Karsten; Stevens, Bjorn; Rast, Sebastian; Schutgens, Nick; Stier, Philip

2015-04-01

The detailed treatment of aerosol in global modeling is complex and time-consuming. Thus simplified approaches are investigated, which prescribe 4D (space and time) distributions of aerosol optical properties and of aerosol microphysical properties. Aerosol optical properties are required to assess aerosol direct radiative effects and aerosol microphysical properties (in terms of their ability as aerosol nuclei to modify cloud droplet concentrations) are needed to address the indirect aerosol impact on cloud properties. Following the simplifying concept of the monthly gridded (1x1 lat/lon) aerosol climatology (MAC), new approaches are presented and evaluated against more detailed methods, including comparisons to detailed simulations with complex aerosol component modules.

In silico approaches to identify novel myeloid cell leukemia-1 (Mcl-1) inhibitors for treatment of cancer.

PubMed

Ren, Ji-Xia; Li, Cheng-Ping; Zhou, Xiu-Ling; Cao, Xue-Song; Xie, Yong

2017-08-22

Myeloid cell leukemia-1 (Mcl-1) has been a validated and attractive target for cancer therapy. Over-expression of Mcl-1 in many cancers allows cancer cells to evade apoptosis and contributes to the resistance to current chemotherapeutics. Here, we identified new Mcl-1 inhibitors using a multi-step virtual screening approach. First, based on two different ligand-receptor complexes, 20 pharmacophore models were established by simultaneously using 'Receptor-Ligand Pharmacophore Generation' method and manual build feature method, and then carefully validated by a test database. Then, pharmacophore-based virtual screening (PB-VS) could be performed by using the 20 pharmacophore models. In addition, docking study was used to predict the possible binding poses of compounds, and the docking parameters were optimized before performing docking-based virtual screening (DB-VS). Moreover, a 3D QSAR model was established by applying the 55 aligned Mcl-1 inhibitors. The 55 inhibitors sharing the same scaffold were docked into the Mcl-1 active site before alignment, then the inhibitors with possible binding conformations were aligned. For the training set, the 3D QSAR model gave a correlation coefficient r 2 of 0.996; for the test set, the correlation coefficient r 2 was 0.812. Therefore, the developed 3D QSAR model was a good model, which could be applied for carrying out 3D QSAR-based virtual screening (QSARD-VS). After the above three virtual screening methods orderly filtering, 23 potential inhibitors with novel scaffolds were identified. Furthermore, we have discussed in detail the mapping results of two potent compounds onto pharmacophore models, 3D QSAR model, and the interactions between the compounds and active site residues.

MolPrint3D: Enhanced 3D Printing of Ball-and-Stick Molecular Models

ERIC Educational Resources Information Center

Paukstelis, Paul J.

2018-01-01

The increased availability of noncommercial 3D printers has provided instructors and students improved access to printing technology. However, printing complex ball-and-stick molecular structures faces distinct challenges, including the need for support structures that increase with molecular complexity. MolPrint3D is a software add-on for the…

Multi-scale modeling of urban air pollution: development and application of a Street-in-Grid model (v1.0) by coupling MUNICH (v1.0) and Polair3D (v1.8.1)

NASA Astrophysics Data System (ADS)

Kim, Youngseob; Wu, You; Seigneur, Christian; Roustan, Yelva

2018-02-01

A new multi-scale model of urban air pollution is presented. This model combines a chemistry-transport model (CTM) that includes a comprehensive treatment of atmospheric chemistry and transport on spatial scales down to 1 km and a street-network model that describes the atmospheric concentrations of pollutants in an urban street network. The street-network model is the Model of Urban Network of Intersecting Canyons and Highways (MUNICH), which consists of two main components: a street-canyon component and a street-intersection component. MUNICH is coupled to the Polair3D CTM of the Polyphemus air quality modeling platform to constitute the Street-in-Grid (SinG) model. MUNICH is used to simulate the concentrations of the chemical species in the urban canopy, which is located in the lowest layer of Polair3D, and the simulation of pollutant concentrations above rooftops is performed with Polair3D. Interactions between MUNICH and Polair3D occur at roof level and depend on a vertical mass transfer coefficient that is a function of atmospheric turbulence. SinG is used to simulate the concentrations of nitrogen oxides (NOx) and ozone (O3) in a Paris suburb. Simulated concentrations are compared to NOx concentrations measured at two monitoring stations within a street canyon. SinG shows better performance than MUNICH for nitrogen dioxide (NO2) concentrations. However, both SinG and MUNICH underestimate NOx. For the case study considered, the model performance for NOx concentrations is not sensitive to using a complex chemistry model in MUNICH and the Leighton NO-NO2-O3 set of reactions is sufficient.

Three-dimensional Magnetotelluric Modeling of the Pohukuloa Training Area, Hawaii Island

NASA Astrophysics Data System (ADS)

Thomas, D. M.; Lienert, B. R.; Wallin, E.

2015-12-01

We report the results of 3D modeling of magnetotelluric (MT) data collected in the Pohakuloa Training Area (PTA) on the saddle between Mauna Loa and Mauna Kea volcanoes on Hawaii Island. We have previously used lower frequency MT data to construct 1D and 2D resistivity profiles in this area and confirmed the presence of a low-resistivity region at depths of about 2 km. One of our drill holes in PTA had previously encountered temperatures of 150 C at a similar depth. However, our 1D and 2D models were unable to fit features of the data that we suspected were due to 3D variations in subsurface resistivity. For the 3D modeling, we reprocessed the higher frequency data (1 kHz sampling rate) which were available at all 20 sites. We were then able to obtain complex impedances at frequencies of 0.5-500 Hz to use for the 3D inversion. We used Siripunvaraporn's 3D inversion method to obtain resistivities in a rectangular array of 0.5x0.5x0.25 km blocks spanning the areal extent of the stations down to a depth of 2.5 km. The results confirmed that much of the anomalous data could be explained by near-surface 3D variations in resistivity. The underlying conductor of 5-10 ohm-m at 2 km depth now appears to extend over the entire survey area.

Comparison of different models for non-invasive FFR estimation

NASA Astrophysics Data System (ADS)

Mirramezani, Mehran; Shadden, Shawn

2017-11-01

Coronary artery disease is a leading cause of death worldwide. Fractional flow reserve (FFR), derived from invasively measuring the pressure drop across a stenosis, is considered the gold standard to diagnose disease severity and need for treatment. Non-invasive estimation of FFR has gained recent attention for its potential to reduce patient risk and procedural cost versus invasive FFR measurement. Non-invasive FFR can be obtained by using image-based computational fluid dynamics to simulate blood flow and pressure in a patient-specific coronary model. However, 3D simulations require extensive effort for model construction and numerical computation, which limits their routine use. In this study we compare (ordered by increasing computational cost/complexity): reduced-order algebraic models of pressure drop across a stenosis; 1D, 2D (multiring) and 3D CFD models; as well as 3D FSI for the computation of FFR in idealized and patient-specific stenosis geometries. We demonstrate the ability of an appropriate reduced order algebraic model to closely predict FFR when compared to FFR from a full 3D simulation. This work was supported by the NIH, Grant No. R01-HL103419.

Proteins from Multiple Metabolic Pathways Associate with Starch Biosynthetic Enzymes in High Molecular Weight Complexes: A Model for Regulation of Carbon Allocation in Maize Amyloplasts1[C][W][OA

PubMed Central

Hennen-Bierwagen, Tracie A.; Lin, Qiaohui; Grimaud, Florent; Planchot, Véronique; Keeling, Peter L.; James, Martha G.; Myers, Alan M.

2009-01-01

Starch biosynthetic enzymes from maize (Zea mays) and wheat (Triticum aestivum) amyloplasts exist in cell extracts in high molecular weight complexes; however, the nature of those assemblies remains to be defined. This study tested the interdependence of the maize enzymes starch synthase IIa (SSIIa), SSIII, starch branching enzyme IIb (SBEIIb), and SBEIIa for assembly into multisubunit complexes. Mutations that eliminated any one of those proteins also prevented the others from assembling into a high molecular mass form of approximately 670 kD, so that SSIII, SSIIa, SBEIIa, and SBEIIb most likely all exist together in the same complex. SSIIa, SBEIIb, and SBEIIa, but not SSIII, were also interdependent for assembly into a complex of approximately 300 kD. SSIII, SSIIa, SBEIIa, and SBEIIb copurified through successive chromatography steps, and SBEIIa, SBEIIb, and SSIIa coimmunoprecipitated with SSIII in a phosphorylation-dependent manner. SBEIIa and SBEIIb also were retained on an affinity column bearing a specific conserved fragment of SSIII located outside of the SS catalytic domain. Additional proteins that copurified with SSIII in multiple biochemical methods included the two known isoforms of pyruvate orthophosphate dikinase (PPDK), large and small subunits of ADP-glucose pyrophosphorylase, and the sucrose synthase isoform SUS-SH1. PPDK and SUS-SH1 required SSIII, SSIIa, SBEIIa, and SBEIIb for assembly into the 670-kD complex. These complexes may function in global regulation of carbon partitioning between metabolic pathways in developing seeds. PMID:19168640

Intermolecular dissociation energies of dispersively bound complexes of aromatics with noble gases and nitrogen

NASA Astrophysics Data System (ADS)

Knochenmuss, Richard; Sinha, Rajeev K.; Leutwyler, Samuel

2018-04-01

We measured accurate intermolecular dissociation energies D0 of the supersonic jet-cooled complexes of 1-naphthol (1NpOH) with the noble gases Ne, Ar, Kr, and Xe and with N2, using the stimulated-emission pumping resonant two-photon ionization method. The ground-state values D0(S0) for the 1NpOHṡS complexes with S= Ar, Kr, Xe, and N2 were bracketed to be within ±3.5%; they are 5.67 ± 0.05 kJ/mol for S = Ar, 7.34 ± 0.07 kJ/mol for S = Kr, 10.8 ± 0.28 kJ/mol for S = Xe, 6.67 ± 0.08 kJ/mol for isomer 1 of the 1NpOHṡN2 complex, and 6.62 ± 0.22 kJ/mol for the corresponding isomer 2. For S = Ne, the upper limit is D0 < 3.36 kJ/mol. The dissociation energies increase by 1%-5% upon S0 → S1 excitation of the complexes. Three dispersion-corrected density functional theory (DFT-D) methods (B97-D3, B3LYP-D3, and ωB97X-D) predict that the most stable form of these complexes involves dispersive binding to the naphthalene "face." A more weakly bound edge isomer is predicted in which the S moiety is H-bonded to the OH group of 1NpOH; however, no edge isomers were observed experimentally. The B97-D3 calculated dissociation energies D0(S0) of the face complexes with Ar, Kr, and N2 agree with the experimental values within <5%, but the D0(S0) for Xe is 12% too low. The B3LYP-D3 and ωB97X-D calculated D0(S0) values exhibit larger deviations to both larger and smaller dissociation energies. For comparison to 1-naphthol, we calculated the D0(S0) of the carbazole complexes with S = Ne, Ar, Kr, Xe, and N2 using the same DFT-D methods. The respective experimental values have been previously determined to be within <2%. Again, the B97-D3 results are in the best overall agreement with experiment.

SmaggIce 2D Version 1.8: Software Toolkit Developed for Aerodynamic Simulation Over Iced Airfoils

NASA Technical Reports Server (NTRS)

Choo, Yung K.; Vickerman, Mary B.

2005-01-01

SmaggIce 2D version 1.8 is a software toolkit developed at the NASA Glenn Research Center that consists of tools for modeling the geometry of and generating the grids for clean and iced airfoils. Plans call for the completed SmaggIce 2D version 2.0 to streamline the entire aerodynamic simulation process--the characterization and modeling of ice shapes, grid generation, and flow simulation--and to be closely coupled with the public-domain application flow solver, WIND. Grid generated using version 1.8, however, can be used by other flow solvers. SmaggIce 2D will help researchers and engineers study the effects of ice accretion on airfoil performance, which is difficult to do with existing software tools because of complex ice shapes. Using SmaggIce 2D, when fully developed, to simulate flow over an iced airfoil will help to reduce the cost of performing flight and wind-tunnel tests for certifying aircraft in natural and simulated icing conditions.

Asteroid age distributions determined by space weathering and collisional evolution models

NASA Astrophysics Data System (ADS)

Willman, Mark; Jedicke, Robert

2011-01-01

We provide evidence of consistency between the dynamical evolution of main belt asteroids and their color evolution due to space weathering. The dynamical age of an asteroid's surface (Bottke, W.F., Durda, D.D., Nesvorný, D., Jedicke, R., Morbidelli, A., Vokrouhlický, D., Levison, H. [2005]. Icarus 175 (1), 111-140; Nesvorný, D., Jedicke, R., Whiteley, R.J., Ivezić, Ž. [2005]. Icarus 173, 132-152) is the time since its last catastrophic disruption event which is a function of the object's diameter. The age of an S-complex asteroid's surface may also be determined from its color using a space weathering model (e.g. Willman, M., Jedicke, R., Moskovitz, N., Nesvorný, D., Vokrouhlický, D., Mothé-Diniz, T. [2010]. Icarus 208, 758-772; Jedicke, R., Nesvorný, D., Whiteley, R.J., Ivezić, Ž., Jurić, M. [2004]. Nature 429, 275-277; Willman, M., Jedicke, R., Nesvorny, D., Moskovitz, N., Ivezić, Ž., Fevig, R. [2008]. Icarus 195, 663-673. We used a sample of 95 S-complex asteroids from SMASS and obtained their absolute magnitudes and u, g, r, i, z filter magnitudes from SDSS. The absolute magnitudes yield a size-derived age distribution. The u, g, r, i, z filter magnitudes lead to the principal component color which yields a color-derived age distribution by inverting our color-age relationship, an enhanced version of the 'dual τ' space weathering model of Willman et al. (2010). We fit the size-age distribution to the enhanced dual τ model and found characteristic weathering and gardening times of τw = 2050 ± 80 Myr and τg=4400-500+700Myr respectively. The fit also suggests an initial principal component color of -0.05 ± 0.01 for fresh asteroid surface with a maximum possible change of the probable color due to weathering of Δ PC = 1.34 ± 0.04. Our predicted color of fresh asteroid surface matches the color of fresh ordinary chondritic surface of PC1 = 0.17 ± 0.39.

D Modelling and Rapid Prototyping for Cardiovascular Surgical Planning - Two Case Studies

NASA Astrophysics Data System (ADS)

Nocerino, E.; Remondino, F.; Uccheddu, F.; Gallo, M.; Gerosa, G.

2016-06-01

In the last years, cardiovascular diagnosis, surgical planning and intervention have taken advantages from 3D modelling and rapid prototyping techniques. The starting data for the whole process is represented by medical imagery, in particular, but not exclusively, computed tomography (CT) or multi-slice CT (MCT) and magnetic resonance imaging (MRI). On the medical imagery, regions of interest, i.e. heart chambers, valves, aorta, coronary vessels, etc., are segmented and converted into 3D models, which can be finally converted in physical replicas through 3D printing procedure. In this work, an overview on modern approaches for automatic and semiautomatic segmentation of medical imagery for 3D surface model generation is provided. The issue of accuracy check of surface models is also addressed, together with the critical aspects of converting digital models into physical replicas through 3D printing techniques. A patient-specific 3D modelling and printing procedure (Figure 1), for surgical planning in case of complex heart diseases was developed. The procedure was applied to two case studies, for which MCT scans of the chest are available. In the article, a detailed description on the implemented patient-specific modelling procedure is provided, along with a general discussion on the potentiality and future developments of personalized 3D modelling and printing for surgical planning and surgeons practice.

Four coordination polymers based on 5-tert-butyl isophthalic acid and rigid bis(imidazol-1yl)benzene linkers: Synthesis, luminescence detection of acetone and optical properties

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

Arıcı, Mürsel, E-mail: marici@ogu.edu.tr; Zafer Yeşilel, Okan; Büyükgüngör, Orhan

Four coordination polymers including, [Co(µ-Htbip){sub 2}(µ-dib)]{sub n} (1), [Co(µ-tbip)(µ-dmib){sub 0.5}]{sub n} (2), [Zn{sub 2}(µ-tbip)(µ{sub 3}-tbip)(µ-dmib){sub 1.5}]{sub n} (3) and [Cd(µ{sub 3}-tbip)(µ-dib){sub 0.5} (H{sub 2}O)]{sub n} (4) (tbip: 5-tert-butylisophthalate, dib: 1,4-bis(imidazol-1yl)benzene, dmib: 1,4-bis(imidazol-1yl)-2,5-dimethylbenzene), were hydrothermally synthesized and characterized by elemental analysis, IR spectra, single crystal and powder X-ray diffraction and thermal analysis (TG/DTA). The structural diversity is observed depending on ligands and coordination number of metal centers in the synthesized complexes. The tbip ligand displayed five different coordination modes in its complexes. In 1 and 2, complex 1 is 3D framework with the dia topology while complex 2 has 2D structuremore » with the sql topology depending on coordination geometries of Co ions. Complex 3 is 3D framework with the fsh 4,6-conn topology and complex 4 has 2D 4-connected sql topology. Photoluminescent properties of complex 3 dispersed in various organic solvents were investigated and the results showed that 3 dispersed in methanol could be used as a fluorescent sensor for the detection of acetone. Moreover, thermal and optical properties of the complexes were also studied. - Graphical abstract: Four coordination polymers were hydrothermally synthesized and characterized by various techniques. The complexes showed the structural diversity depending on ligands and coordination number of metal centers. The tbip ligand displayed four different coordination modes in its complexes. In 1 and 2, complexes 1 and 2 are 3D and 2D structures with the dia and sql topologies depending on coordination geometries of Co ions, respectively. Complexes 3 and 4 are 3D and 2D structures with the fsh 4,6-conn and sql topology, respectively. Photoluminescent properties of complex 3 dispersed in various organic solvents were investigated and the results showed that 3 dispersed in methanol could be used as a fluorescent sensor for the detection of acetone. Moreover, thermal and optical properties of the complexes were also studied. - Highlights: • Four new 2D and 3D coordination polymers with 5-tert-butyl isophthalic acid and rigid bis(imidazol-1yl)benzene linkers. • The structural diversity depending on ligands and coordination number of metal centers. • Fluorescent sensor for the detection of acetone.« less

Design for an aging brain.

PubMed

Thaler, David S

2002-01-01

Vaillancourt and Newell (Neurobiol. of Aging 2001) show that although many aging systems decrease in complexity as anticipated by Lipsitz and Goldberger (JAMA 1992), other aging systems increase in complexity. Vaillancourt and Newell explain the discrepancy by proposing that systems with a point attractor decrease in complexity with age, whereas those with an oscillating attractor increase in complexity with age. Vaillancourt and Newell are certainly correct that no one direction fits all results. Aging and death sometimes follow from a system being too simple, or, too complex. A perspective, based on the work of W. Ross Ashby (1956 and http://pespmc1.vub.ac.be/ASHBBOOK.html) is used in this commentary to consider why some systems become apparently more simple and others more complex as they age. In this Ashby-inspired view the measured complexity of a system's Responses to Disturbances is proportional to the ratio D/R, where D and R are sets containing the variety of possible disturbances and responses. The model expands on Ashby's by proposing that D consists of two components, Dp and Du. Dp consists of disturbances that are a function of the system's perception. Responses to Dp are often anticipatory and the response itself dominates the outcome. Du are disturbances that are unavoidable. Outcomes decrease or increase in measured entropy as a function of changes in (Dp + Du)/R. The variety of elements in both Dp and R decrease with age. When D/R decreases with age, the system shows less complexity. Conversely when D/R increases with Age, the results become more entropic.

Safety Risk Knowledge Elicitation in Support of Aeronautical R and D Portfolio Management: A Case Study

NASA Technical Reports Server (NTRS)

Shih, Ann T.; Ancel, Ersin; Jones, Sharon Monica; Reveley, Mary S.; Luxhoj, James T.

2012-01-01

Aviation is a problem domain characterized by a high level of system complexity and uncertainty. Safety risk analysis in such a domain is especially challenging given the multitude of operations and diverse stakeholders. The Federal Aviation Administration (FAA) projects that by 2025 air traffic will increase by more than 50 percent with 1.1 billion passengers a year and more than 85,000 flights every 24 hours contributing to further delays and congestion in the sky (Circelli, 2011). This increased system complexity necessitates the application of structured safety risk analysis methods to understand and eliminate where possible, reduce, and/or mitigate risk factors. The use of expert judgments for probabilistic safety analysis in such a complex domain is necessary especially when evaluating the projected impact of future technologies, capabilities, and procedures for which current operational data may be scarce. Management of an R&D product portfolio in such a dynamic domain needs a systematic process to elicit these expert judgments, process modeling results, perform sensitivity analyses, and efficiently communicate the modeling results to decision makers. In this paper a case study focusing on the application of an R&D portfolio of aeronautical products intended to mitigate aircraft Loss of Control (LOC) accidents is presented. In particular, the knowledge elicitation process with three subject matter experts who contributed to the safety risk model is emphasized. The application and refinement of a verbal-numerical scale for conditional probability elicitation in a Bayesian Belief Network (BBN) is discussed. The preliminary findings from this initial step of a three-part elicitation are important to project management practitioners as they illustrate the vital contribution of systematic knowledge elicitation in complex domains.

3-D inversion of complex magnetotelluric data from an Archean-Proterozoic terrain in northeastern São Francisco Craton, Brazil

NASA Astrophysics Data System (ADS)

Bologna, Mauricio S.; Egbert, Gary D.; Padilha, Antonio L.; Pádua, Marcelo B.; Vitorello, Ícaro

2017-09-01

We present a magnetotelluric (MT) study in the northeastern part of the São Francisco Craton that encompasses an Archean-Proterozoic terrain, the Serrinha Block, breached by a rift basin developed mostly in Early Cretaceous times during the opening of the South Atlantic Ocean. Even though the MT sites are regularly spaced, the profiles have different orientations from one another, making the data distribution over the area highly uneven and therefore non-ideal for 3-D modeling. However, the data set is very complex, with dimensionality analysis indicating prevalence of 3-D geoelectric structure. Results from 3-D inversion are evaluated for robustness and potentiality for yielding tectonic information. At upper crustal depths, the resulting 3-D model is coherent with surface geology, whereas at mid and lower crustal depths more cryptic structures are revealed, likely of Palaeoproterozoic age. The most striking features in the model are several strong (∼1 Ωṡm) crustal conductors beneath the central part of the Serrinha Block, which we attribute to a Palaeoproterozoic oceanic plate subduction and arc-continent collision event involving the Rio Itapicuru Greenstone Belt and the basement of the Serrinha Block. The west-dipping geometry of these conductors provides a constraint on subduction polarity and gives support to tectonic evolutionary models proposing that the Rio Itapicuru Belt was formed in an island arc environment.

Structure, Dynamics, and Interaction of Mycobacterium tuberculosis (Mtb) DprE1 and DprE2 Examined by Molecular Modeling, Simulation, and Electrostatic Studies

PubMed Central

Bhutani, Isha; Loharch, Saurabh; Gupta, Pawan; Madathil, Rethi; Parkesh, Raman

2015-01-01

The enzymes decaprenylphosphoryl-β-D-ribose oxidase (DprE1) and decaprenylphosphoryl-β-D-ribose-2-epimerase (DprE2) catalyze epimerization of decaprenylphosporyl ribose (DPR) todecaprenylphosporyl arabinose (DPA) and are critical for the survival of Mtb. Crystal structures of DprE1 so far reported display significant disordered regions and no structural information is known for DprE2. We used homology modeling, protein threading, molecular docking and dynamics studies to investigate the structural and dynamic features of Mtb DprE1 and DprE2 and DprE1-DprE2 complex. A three-dimensional model for DprE2 was generated using the threading approach coupled with ab initio modeling. A 50 ns simulation of DprE1 and DprE2 revealed the overall stability of the structures. Principal Component Analysis (PCA) demonstrated the convergence of sampling in both DprE1 and DprE2. In DprE1, residues in the 269–330 area showed considerable fluctuation in agreement with the regions of disorder observed in the reported crystal structures. In DprE2, large fluctuations were detected in residues 95–113, 146–157, and 197–226. The study combined docking and MD simulation studies to map and characterize the key residues involved in DprE1-DprE2 interaction. A 60 ns MD simulation for DprE1-DprE2 complex was also performed. Analysis of data revealed that the docked complex is stabilized by H-bonding, hydrophobic and ionic interactions. The key residues of DprE1 involved in DprE1-DprE2 interactions belong to the disordered region. We also examined the docked complex of DprE1-BTZ043 to investigate the binding pocket of DprE1 and its interactions with the inhibitor BTZ043. In summary, we hypothesize that DprE1-DprE2 interaction is crucial for the synthesis of DPA and DprE1-DprE2 complex may be a new therapeutic target amenable to pharmacological validation. The findings have important implications in tuberculosis (TB) drug discovery and will facilitate drug development efforts against TB. PMID:25789990

Structure, dynamics, and interaction of Mycobacterium tuberculosis (Mtb) DprE1 and DprE2 examined by molecular modeling, simulation, and electrostatic studies.

PubMed

Bhutani, Isha; Loharch, Saurabh; Gupta, Pawan; Madathil, Rethi; Parkesh, Raman

2015-01-01

The enzymes decaprenylphosphoryl-β-D-ribose oxidase (DprE1) and decaprenylphosphoryl-β-D-ribose-2-epimerase (DprE2) catalyze epimerization of decaprenylphosporyl ribose (DPR) todecaprenylphosporyl arabinose (DPA) and are critical for the survival of Mtb. Crystal structures of DprE1 so far reported display significant disordered regions and no structural information is known for DprE2. We used homology modeling, protein threading, molecular docking and dynamics studies to investigate the structural and dynamic features of Mtb DprE1 and DprE2 and DprE1-DprE2 complex. A three-dimensional model for DprE2 was generated using the threading approach coupled with ab initio modeling. A 50 ns simulation of DprE1 and DprE2 revealed the overall stability of the structures. Principal Component Analysis (PCA) demonstrated the convergence of sampling in both DprE1 and DprE2. In DprE1, residues in the 269-330 area showed considerable fluctuation in agreement with the regions of disorder observed in the reported crystal structures. In DprE2, large fluctuations were detected in residues 95-113, 146-157, and 197-226. The study combined docking and MD simulation studies to map and characterize the key residues involved in DprE1-DprE2 interaction. A 60 ns MD simulation for DprE1-DprE2 complex was also performed. Analysis of data revealed that the docked complex is stabilized by H-bonding, hydrophobic and ionic interactions. The key residues of DprE1 involved in DprE1-DprE2 interactions belong to the disordered region. We also examined the docked complex of DprE1-BTZ043 to investigate the binding pocket of DprE1 and its interactions with the inhibitor BTZ043. In summary, we hypothesize that DprE1-DprE2 interaction is crucial for the synthesis of DPA and DprE1-DprE2 complex may be a new therapeutic target amenable to pharmacological validation. The findings have important implications in tuberculosis (TB) drug discovery and will facilitate drug development efforts against TB.

Insights from Molecular Dynamics Simulations: Structural Basis for the V567D Mutation-Induced Instability of Zebrafish Alpha-Dystroglycan and Comparison with the Murine Model

PubMed Central

Pirolli, Davide; Sciandra, Francesca; Bozzi, Manuela; Giardina, Bruno; Brancaccio, Andrea; De Rosa, Maria Cristina

2014-01-01

A missense amino acid mutation of valine to aspartic acid in 567 position of alpha-dystroglycan (DG), identified in dag1-mutated zebrafish, results in a reduced transcription and a complete absence of the protein. Lacking experimental structural data for zebrafish DG domains, the detailed mechanism for the observed mutation-induced destabilization of the DG complex and membrane damage, remained unclear. With the aim to contribute to a better clarification of the structure-function relationships featuring the DG complex, three-dimensional structural models of wild-type and mutant (V567D) C-terminal domain of alpha-DG from zebrafish were constructed by a template-based modelling approach. We then ran extensive molecular dynamics (MD) simulations to reveal the structural and dynamic properties of the C-terminal domain and to evaluate the effect of the single mutation on alpha-DG stability. A comparative study has been also carried out on our previously generated model of murine alpha-DG C-terminal domain including the I591D mutation, which is topologically equivalent to the V567D mutation found in zebrafish. Trajectories from MD simulations were analyzed in detail, revealing extensive structural disorder involving multiple beta-strands in the mutated variant of the zebrafish protein whereas local effects have been detected in the murine protein. A biochemical analysis of the murine alpha-DG mutant I591D confirmed a pronounced instability of the protein. Taken together, the computational and biochemical analysis suggest that the V567D/I591D mutation, belonging to the G beta-strand, plays a key role in inducing a destabilization of the alpha-DG C-terminal Ig-like domain that could possibly affect and propagate to the entire DG complex. The structural features herein identified may be of crucial help to understand the molecular basis of primary dystroglycanopathies. PMID:25078606

Insights from molecular dynamics simulations: structural basis for the V567D mutation-induced instability of zebrafish alpha-dystroglycan and comparison with the murine model.

PubMed

Pirolli, Davide; Sciandra, Francesca; Bozzi, Manuela; Giardina, Bruno; Brancaccio, Andrea; De Rosa, Maria Cristina

2014-01-01

A missense amino acid mutation of valine to aspartic acid in 567 position of alpha-dystroglycan (DG), identified in dag1-mutated zebrafish, results in a reduced transcription and a complete absence of the protein. Lacking experimental structural data for zebrafish DG domains, the detailed mechanism for the observed mutation-induced destabilization of the DG complex and membrane damage, remained unclear. With the aim to contribute to a better clarification of the structure-function relationships featuring the DG complex, three-dimensional structural models of wild-type and mutant (V567D) C-terminal domain of alpha-DG from zebrafish were constructed by a template-based modelling approach. We then ran extensive molecular dynamics (MD) simulations to reveal the structural and dynamic properties of the C-terminal domain and to evaluate the effect of the single mutation on alpha-DG stability. A comparative study has been also carried out on our previously generated model of murine alpha-DG C-terminal domain including the I591D mutation, which is topologically equivalent to the V567D mutation found in zebrafish. Trajectories from MD simulations were analyzed in detail, revealing extensive structural disorder involving multiple beta-strands in the mutated variant of the zebrafish protein whereas local effects have been detected in the murine protein. A biochemical analysis of the murine alpha-DG mutant I591D confirmed a pronounced instability of the protein. Taken together, the computational and biochemical analysis suggest that the V567D/I591D mutation, belonging to the G beta-strand, plays a key role in inducing a destabilization of the alpha-DG C-terminal Ig-like domain that could possibly affect and propagate to the entire DG complex. The structural features herein identified may be of crucial help to understand the molecular basis of primary dystroglycanopathies.

Polyphase tertiary fold-and-thrust tectonics in the Belluno Dolomites: new mapping, kinematic analysis, and 3D modelling

NASA Astrophysics Data System (ADS)

Chistolini, Filippo; Bistacchi, Andrea; Massironi, Matteo; Consonni, Davide; Cortinovis, Silvia

2014-05-01

The Belluno Dolomites are comprised in the eastern sector of the Southern Alps, which corresponds to the fold-and-thrust belt at the retro-wedge of the Alpine collisional orogen. They are characterized by a complex and polyphase fold-and-thrust tectonics, highlighted by multiple thrust sheets and thrust-related folding. We have studied this tectonics in the Vajont area where a sequence of Jurassic, Cretaceous and Tertiary units have been involved in multiple deformations. The onset of contractional tectonics in this part of the Alps is constrained to be Tertiary (likely Post-Eocene) by structural relationships with the Erto Flysch, whilst in the Mesozoic tectonics was extensional. We have recognized two contractional deformation phases (D1 and D2 in the following), of which only the second was mentioned in previous studies of the area and attributed to the Miocene Neoalpine event. D1 and D2 are characterized by roughly top-to-WSW (possibly Dinaric) and top-to-S (Alpine) transport directions respectively, implying a 90° rotation of the regional-scale shortening axis, and resulting in complex thrust and fold interference and reactivation patterns. Geological mapping and detailed outcrop-scale kinematic analysis allowed us to characterize the kinematics and chronology of deformations. Particularly, relative chronology was unravelled thanks to (1) diagnostic fold interference patterns and (2) crosscutting relationships between thrust faults and thrust-related folds. A km-scale D1 syncline, filled with the Eocene Erto Flysch and "decapitated" by a D2 thrust fault, provides the best map-scale example of crosscutting relationships allowing to reconstruct the faulting history. Due to the strong competence contrast between Jurassic carbonates and Tertiary flysch, in this syncline spectacular duplexes were also developed during D2. In order to quantitatively characterize the complex interference pattern resulting from two orthogonal thrusting and folding events, we performed a dip-domain analysis that allowed to categorize the different fold limbs and reduce the uncertainty in the reconstruction of the fault network topology in map view. This enabled us to reconstruct a high-quality, low-uncertainty 3D structural and geological model, which unambiguously proves that deformations with a top-to-WSW Dinaric transport direction propagate farther to the west than previously supposed in this part of the Southern Alps. Our new structural reconstruction of the Vajont valley have also clarified the structural control on the 1963 catastrophic landslide (which caused over 2000 losses). Besides being a challenging natural laboratory for testing analysis and modelling methodologies to be used when reconstructing in 3D this kind of complex interference structures, the Vajont area also provides useful clues on the still-enigmatic structures in the frontal part of the Friuli-Venetian Southern Alps, buried in the Venetian Plain foredeep. These include active seismogenic thrust-faults and, at the same time, represent a growing interest for the oil industry.

Mutations of Photosystem II D1 Protein That Empower Efficient Phenotypes of Chlamydomonas reinhardtii under Extreme Environment in Space

PubMed Central

Lambreva, Maya D.; Antonacci, Amina; Pastorelli, Sandro; Bertalan, Ivo; Johanningmeier, Udo; Mattoo, Autar K.

2013-01-01

Space missions have enabled testing how microorganisms, animals and plants respond to extra-terrestrial, complex and hazardous environment in space. Photosynthetic organisms are thought to be relatively more prone to microgravity, weak magnetic field and cosmic radiation because oxygenic photosynthesis is intimately associated with capture and conversion of light energy into chemical energy, a process that has adapted to relatively less complex and contained environment on Earth. To study the direct effect of the space environment on the fundamental process of photosynthesis, we sent into low Earth orbit space engineered and mutated strains of the unicellular green alga, Chlamydomonas reinhardtii, which has been widely used as a model of photosynthetic organisms. The algal mutants contained specific amino acid substitutions in the functionally important regions of the pivotal Photosystem II (PSII) reaction centre D1 protein near the QB binding pocket and in the environment surrounding Tyr-161 (YZ) electron acceptor of the oxygen-evolving complex. Using real-time measurements of PSII photochemistry, here we show that during the space flight while the control strain and two D1 mutants (A250L and V160A) were inefficient in carrying out PSII activity, two other D1 mutants, I163N and A251C, performed efficient photosynthesis, and actively re-grew upon return to Earth. Mimicking the neutron irradiation component of cosmic rays on Earth yielded similar results. Experiments with I163N and A251C D1 mutants performed on ground showed that they are better able to modulate PSII excitation pressure and have higher capacity to reoxidize the QA − state of the primary electron acceptor. These results highlight the contribution of D1 conformation in relation to photosynthesis and oxygen production in space. PMID:23691201

Intraoperative utilization of advanced imaging modalities in a complex kidney stone case: a pilot case study.

PubMed

Christiansen, Andrew R; Shorti, Rami M; Smith, Cory D; Prows, William C; Bishoff, Jay T

2018-05-01

Despite the increasing use of advanced 3D imaging techniques and 3D printing, these techniques have not yet been comprehensively compared in a surgical setting. The purpose of this study is to explore the effectiveness of five different advanced imaging modalities during a complex renal surgical procedure. A patient with a horseshoe kidney and multiple large, symptomatic stones that had failed Extracorporeal Shock Wave Lithotripsy (ESWL) and ureteroscopy treatment was used for this evaluation. CT data were used to generate five different imaging modalities, including a 3D printed model, three different volume rendered models, and a geometric CAD model. A survey was used to evaluate the quality and breadth of the imaging modalities during four different phases of the laparoscopic procedure. In the case of a complex kidney procedure, the CAD model, 3D print, volume render on an autostereoscopic 3D display, interactive and basic volume render models demonstrated added insight and complemented the surgical procedure. CAD manual segmentation allowed tissue layers and/or kidney stones to be made colorful and semi-transparent, allowing easier navigation through abnormal vasculature. The 3D print allowed for simultaneous visualization of renal pelvis and surrounding vasculature. Our preliminary exploration indicates that various advanced imaging modalities, when properly utilized and supported during surgery, can be useful in complementing the CT data and laparoscopic display. This study suggests that various imaging modalities, such as ones utilized in this case, can be beneficial intraoperatively depending on the surgical step involved and may be more helpful than 3D printed models. We also present factors to consider when evaluating advanced imaging modalities during complex surgery.

Vehicle Surveillance with a Generic, Adaptive, 3D Vehicle Model.

PubMed

Leotta, Matthew J; Mundy, Joseph L

2011-07-01

In automated surveillance, one is often interested in tracking road vehicles, measuring their shape in 3D world space, and determining vehicle classification. To address these tasks simultaneously, an effective approach is the constrained alignment of a prior model of 3D vehicle shape to images. Previous 3D vehicle models are either generic but overly simple or rigid and overly complex. Rigid models represent exactly one vehicle design, so a large collection is needed. A single generic model can deform to a wide variety of shapes, but those shapes have been far too primitive. This paper uses a generic 3D vehicle model that deforms to match a wide variety of passenger vehicles. It is adjustable in complexity between the two extremes. The model is aligned to images by predicting and matching image intensity edges. Novel algorithms are presented for fitting models to multiple still images and simultaneous tracking while estimating shape in video. Experiments compare the proposed model to simple generic models in accuracy and reliability of 3D shape recovery from images and tracking in video. Standard techniques for classification are also used to compare the models. The proposed model outperforms the existing simple models at each task.

A surprisingly complex aqueous chemistry of the simplest amino acid. A pulse radiolysis and theoretical study on H/D kinetic isotope effects in the reaction of glycine anions with hydroxyl radicals.

PubMed

Stefanić, I; Ljubić, I; Bonifacić, M; Sabljić, A; Asmus, K-D; Armstrong, D A

2009-04-07

A pulse radiolysis study was carried out of the reaction rate constants and kinetic isotope effects of hydroxyl-radical-induced H/D abstraction from the most-simple alpha-amino acid glycine in its anionic form in water. The rate constants and yields of three predominantly formed radical products, glycyl (NH2-*CH-CO2-), aminomethyl (NH2-*CH2), and aminyl (*NH-CH2-CO2-) radicals, as well as of their partially or fully deuterated analogs, were found to be of comparable magnitude. The primary, secondary, and primary/secondary H/D kinetic isotope effects on the rate constants were determined with respect to each of the three radicals. The unusual variety of products for such an elementary reaction between two small and simple species indicates a complex mechanism with several reactions taking place simultaneously. Thus, a theoretical modeling of the reaction mechanism and kinetics in the gas- and aqueous phase was performed by using the unrestricted density functional theory with the BB1K functional (employing the polarizable continuum model for the aqueous phase), unrestricted coupled cluster UCCSD(T) method, and improved canonical variational theory. Several hydrogen-bonded prereaction complexes and transition states were detected. In particular, the calculations pointed to a significant mechanistic role of the three-electron two-orbital (sigma/sigma* N therefore O) hemibonded prereaction complexes in the aqueous phase. A good agreement with the experimental rate constants and kinetic isotope effects was achieved by downshifting the calculated reaction barriers by 3 kcal mol(-1) and damping the NH(D) stretching frequency by a factor of 0.86.

My Corporis Fabrica: an ontology-based tool for reasoning and querying on complex anatomical models

PubMed Central

2014-01-01

Background Multiple models of anatomy have been developed independently and for different purposes. In particular, 3D graphical models are specially useful for visualizing the different organs composing the human body, while ontologies such as FMA (Foundational Model of Anatomy) are symbolic models that provide a unified formal description of anatomy. Despite its comprehensive content concerning the anatomical structures, the lack of formal descriptions of anatomical functions in FMA limits its usage in many applications. In addition, the absence of connection between 3D models and anatomical ontologies makes it difficult and time-consuming to set up and access to the anatomical content of complex 3D objects. Results First, we provide a new ontology of anatomy called My Corporis Fabrica (MyCF), which conforms to FMA but extends it by making explicit how anatomical structures are composed, how they contribute to functions, and also how they can be related to 3D complex objects. Second, we have equipped MyCF with automatic reasoning capabilities that enable model checking and complex queries answering. We illustrate the added-value of such a declarative approach for interactive simulation and visualization as well as for teaching applications. Conclusions The novel vision of ontologies that we have developed in this paper enables a declarative assembly of different models to obtain composed models guaranteed to be anatomically valid while capturing the complexity of human anatomy. The main interest of this approach is its declarativity that makes possible for domain experts to enrich the knowledge base at any moment through simple editors without having to change the algorithmic machinery. This provides MyCF software environment a flexibility to process and add semantics on purpose for various applications that incorporate not only symbolic information but also 3D geometric models representing anatomical entities as well as other symbolic information like the anatomical functions. PMID:24936286

Definition of (so MIScalled) ''Complexity'' as UTTER-SIMPLICITY!!! Versus Deviations From it as Complicatedness-Measure

NASA Astrophysics Data System (ADS)

Young, F.; Siegel, Edward Carl-Ludwig

2011-03-01

(so MIScalled) "complexity" with INHERENT BOTH SCALE-Invariance Symmetry-RESTORING, AND 1 / w (1.000..) "pink" Zipf-law Archimedes-HYPERBOLICITY INEVITABILITY power-spectrum power-law decay algebraicity. Their CONNECTION is via simple-calculus SCALE-Invariance Symmetry-RESTORING logarithm-function derivative: (d/ d ω) ln(ω) = 1 / ω , i.e. (d/ d ω) [SCALE-Invariance Symmetry-RESTORING](ω) = 1/ ω . Via Noether-theorem continuous-symmetries relation to conservation-laws: (d/ d ω) [inter-scale 4-current 4-div-ergence} = 0](ω) = 1 / ω . Hence (so MIScalled) "complexity" is information inter-scale conservation, in agreement with Anderson-Mandell [Fractals of Brain/Mind, G. Stamov ed.(1994)] experimental-psychology!!!], i.e. (so MIScalled) "complexity" is UTTER-SIMPLICITY!!! Versus COMPLICATEDNESS either PLUS (Additive) VS. TIMES (Multiplicative) COMPLICATIONS of various system-specifics. COMPLICATEDNESS-MEASURE DEVIATIONS FROM complexity's UTTER-SIMPLICITY!!!: EITHER [SCALE-Invariance Symmetry-BREAKING] MINUS [SCALE-Invariance Symmetry-RESTORING] via power-spectrum power-law algebraicity decays DIFFERENCES: ["red"-Pareto] MINUS ["pink"-Zipf Archimedes-HYPERBOLICITY INEVITABILITY]!!!

Functional role of the MrpA- and MrpD-homologous protein subunits in enzyme complexes evolutionary related to respiratory chain complex I.

PubMed

Moparthi, Vamsi K; Kumar, Brijesh; Al-Eryani, Yusra; Sperling, Eva; Górecki, Kamil; Drakenberg, Torbjörn; Hägerhäll, Cecilia

2014-01-01

NADH:quinone oxidoreductase or complex I is a large membrane bound enzyme complex that has evolved from the combination of smaller functional building blocks. Intermediate size enzyme complexes exist in nature that comprise some, but not all of the protein subunits in full size 14-subunit complex I. The membrane spanning complex I subunits NuoL, NuoM and NuoN are homologous to each other and to two proteins from one particular class of Na(+)/H(+) antiporters, denoted MrpA and MrpD. In complex I, these ion transporter protein subunits are prime candidates for harboring important parts of the proton pumping machinery. Using a model system, consisting of Bacillus subtilis MrpA and MrpD deletion strains and a low copy expression plasmid, it was recently demonstrated that NuoN can rescue the strain deleted for MrpD but not that deleted for MrpA, whereas the opposite tendency was seen for NuoL. This demonstrated that the MrpA-type and MrpD-type proteins have unique functional specializations. In this work, the corresponding antiporter-like protein subunits from the smaller enzymes evolutionarily related to complex I were tested in the same model system. The subunits from 11-subunit complex I from Bacillus cereus behaved essentially as those from full size complex I, corroborating that this enzyme should be regarded as a bona fide complex I. The hydrogenase-3 and hydrogenase-4 antiporter-like proteins on the other hand, could substitute equally well for MrpA or MrpD at pH7.4, suggesting that these enzymes have intermediate forms of the antiporter-like proteins, which seemingly lack the functional specificity. © 2013. Published by Elsevier B.V. All rights reserved.

A Case Study in Astronomical 3D Printing: The Mysterious η Carinae

NASA Astrophysics Data System (ADS)

Madura, Thomas I.

2017-05-01

Three-dimensional (3D) printing moves beyond interactive 3D graphics and provides an excellent tool for both visual and tactile learners, since 3D printing can now easily communicate complex geometries and full color information. Some limitations of interactive 3D graphics are also alleviated by 3D printable models, including issues of limited software support, portability, accessibility, and sustainability. We describe the motivations, methods, and results of our work on using 3D printing (1) to visualize and understand the η Car Homunculus nebula and central binary system and (2) for astronomy outreach and education, specifically, with visually impaired students. One new result we present is the ability to 3D print full-color models of η Car’s colliding stellar winds. We also demonstrate how 3D printing has helped us communicate our improved understanding of the detailed structure of η Car’s Homunculus nebula and central binary colliding stellar winds, and their links to each other. Attached to this article are full-color 3D printable files of both a red-blue Homunculus model and the η Car colliding stellar winds at orbital phase 1.045. 3D printing could prove to be vital to how astronomer’s reach out and share their work with each other, the public, and new audiences.

3D Printing of Molecular Models

ERIC Educational Resources Information Center

Gardner, Adam; Olson, Arthur

2016-01-01

Physical molecular models have played a valuable role in our understanding of the invisible nano-scale world. We discuss 3D printing and its use in producing models of the molecules of life. Complex biomolecular models, produced from 3D printed parts, can demonstrate characteristics of molecular structure and function, such as viral self-assembly,…

The Quantitative Criteria Based on the Fractal Dimensions, Entropy, and Lacunarity for the Spatial Distribution of Cancer Cell Nuclei Enable Identification of Low or High Aggressive Prostate Carcinomas

PubMed Central

Waliszewski, Przemyslaw

2016-01-01

Background: Tumor grading, PSA concentration, and stage determine a risk of prostate cancer patients with accuracy of about 70%. An approach based on the fractal geometrical model was proposed to eliminate subjectivity from the evaluation of tumor aggressiveness and to improve the prediction. This study was undertaken to validate classes of equivalence for the spatial distribution of cancer cell nuclei in a larger, independent set of prostate carcinomas. Methods: The global fractal capacity D0, information D1 and correlation D2 dimension, the local fractal dimension (LFD) and the local connected fractal dimension (LCFD), Shannon entropy H and lacunarity λ were measured using computer algorithms in digitalized images of both the reference set (n = 60) and the test set (n = 208) of prostate carcinomas. Results: Prostate carcinomas were re-stratified into seven classes of equivalence. The cut-off D0-values 1.5450, 1.5820, 1.6270, 1.6490, 1.6980, 1.7640 defined the classes from C1 to C7, respectively. The other measures but the D1 failed to define the same classes of equivalence. The pairs (D0, LFD), (D0, H), (D0, λ), (D1, LFD), (D1, H), (D1, λ) characterized the spatial distribution of cancer cell nuclei in each class. The co-application of those measures enabled the subordination of prostate carcinomas to one out of three clusters associated with different tumor aggressiveness. For D0 < 1.5820, LFD < 1.3, LCFD > 1.5, H < 0.7, and λ > 0.8, the class C1 or C2 contains low complexity low aggressive carcinomas exclusively. For D0 > 1.6980, LFD > 1.7644, LCFD > 1.7051, H > 0.9, and λ < 0.7, the class C6 or C7 contains high complexity high aggressive carcinomas. Conclusions: The cut-off D0-values defining the classes of equivalence were validated in this study. The cluster analysis suggested that the number of the subjective Gleason grades and the number of the objective classes of equivalence could be decreased from seven to three without a loss of clinically relevant information. Two novel quantitative criteria based on the complexity and the diversity measures enabled the identification of low or high aggressive prostate carcinomas and should be verified in the future multicenter, randomized studies. PMID:26903883

Accurate, precise, and efficient theoretical methods to calculate anion-π interaction energies in model structures.

PubMed

Mezei, Pál D; Csonka, Gábor I; Ruzsinszky, Adrienn; Sun, Jianwei

2015-01-13

A correct description of the anion-π interaction is essential for the design of selective anion receptors and channels and important for advances in the field of supramolecular chemistry. However, it is challenging to do accurate, precise, and efficient calculations of this interaction, which are lacking in the literature. In this article, by testing sets of 20 binary anion-π complexes of fluoride, chloride, bromide, nitrate, or carbonate ions with hexafluorobenzene, 1,3,5-trifluorobenzene, 2,4,6-trifluoro-1,3,5-triazine, or 1,3,5-triazine and 30 ternary π-anion-π' sandwich complexes composed from the same monomers, we suggest domain-based local-pair natural orbital coupled cluster energies extrapolated to the complete basis-set limit as reference values. We give a detailed explanation of the origin of anion-π interactions, using the permanent quadrupole moments, static dipole polarizabilities, and electrostatic potential maps. We use symmetry-adapted perturbation theory (SAPT) to calculate the components of the anion-π interaction energies. We examine the performance of the direct random phase approximation (dRPA), the second-order screened exchange (SOSEX), local-pair natural-orbital (LPNO) coupled electron pair approximation (CEPA), and several dispersion-corrected density functionals (including generalized gradient approximation (GGA), meta-GGA, and double hybrid density functional). The LPNO-CEPA/1 results show the best agreement with the reference results. The dRPA method is only slightly less accurate and precise than the LPNO-CEPA/1, but it is considerably more efficient (6-17 times faster) for the binary complexes studied in this paper. For 30 ternary π-anion-π' sandwich complexes, we give dRPA interaction energies as reference values. The double hybrid functionals are much more efficient but less accurate and precise than dRPA. The dispersion-corrected double hybrid PWPB95-D3(BJ) and B2PLYP-D3(BJ) functionals perform better than the GGA and meta-GGA functionals for the present test set.

Domain mapping of the Rad51 paralog protein complexes

PubMed Central

Miller, Kristi A.; Sawicka, Dorota; Barsky, Daniel; Albala, Joanna S.

2004-01-01

The five human Rad51 paralogs are suggested to play an important role in the maintenance of genome stability through their function in DNA double-strand break repair. These proteins have been found to form two distinct complexes in vivo, Rad51B–Rad51C–Rad51D–Xrcc2 (BCDX2) and Rad51C–Xrcc3 (CX3). Based on the recent Pyrococcus furiosus Rad51 structure, we have used homology modeling to design deletion mutants of the Rad51 paralogs. The models of the human Rad51B, Rad51C, Xrcc3 and murine Rad51D (mRad51D) proteins reveal distinct N-terminal and C-terminal domains connected by a linker region. Using yeast two-hybrid and co-immunoprecipitation techniques, we have demonstrated that a fragment of Rad51B containing amino acid residues 1–75 interacts with the C-terminus and linker of Rad51C, residues 79–376, and this region of Rad51C also interacts with mRad51D and Xrcc3. We have also determined that the N-terminal domain of mRad51D, residues 4–77, binds to Xrcc2 while the C-terminal domain of mRad51D, residues 77–328, binds Rad51C. By this, we have identified the binding domains of the BCDX2 and CX3 complexes to further characterize the interaction of these proteins and propose a scheme for the three-dimensional architecture of the BCDX2 and CX3 paralog complexes. PMID:14704354

Results of the eruptive column model inter-comparison study

USGS Publications Warehouse

Costa, Antonio; Suzuki, Yujiro; Cerminara, M.; Devenish, Ben J.; Esposti Ongaro, T.; Herzog, Michael; Van Eaton, Alexa; Denby, L.C.; Bursik, Marcus; de' Michieli Vitturi, Mattia; Engwell, S.; Neri, Augusto; Barsotti, Sara; Folch, Arnau; Macedonio, Giovanni; Girault, F.; Carazzo, G.; Tait, S.; Kaminski, E.; Mastin, Larry G.; Woodhouse, Mark J.; Phillips, Jeremy C.; Hogg, Andrew J.; Degruyter, Wim; Bonadonna, Costanza

2016-01-01

This study compares and evaluates one-dimensional (1D) and three-dimensional (3D) numerical models of volcanic eruption columns in a set of different inter-comparison exercises. The exercises were designed as a blind test in which a set of common input parameters was given for two reference eruptions, representing a strong and a weak eruption column under different meteorological conditions. Comparing the results of the different models allows us to evaluate their capabilities and target areas for future improvement. Despite their different formulations, the 1D and 3D models provide reasonably consistent predictions of some of the key global descriptors of the volcanic plumes. Variability in plume height, estimated from the standard deviation of model predictions, is within ~ 20% for the weak plume and ~ 10% for the strong plume. Predictions of neutral buoyancy level are also in reasonably good agreement among the different models, with a standard deviation ranging from 9 to 19% (the latter for the weak plume in a windy atmosphere). Overall, these discrepancies are in the range of observational uncertainty of column height. However, there are important differences amongst models in terms of local properties along the plume axis, particularly for the strong plume. Our analysis suggests that the simplified treatment of entrainment in 1D models is adequate to resolve the general behaviour of the weak plume. However, it is inadequate to capture complex features of the strong plume, such as large vortices, partial column collapse, or gravitational fountaining that strongly enhance entrainment in the lower atmosphere. We conclude that there is a need to more accurately quantify entrainment rates, improve the representation of plume radius, and incorporate the effects of column instability in future versions of 1D volcanic plume models.

Modeling two-phase flow in three-dimensional complex flow-fields of proton exchange membrane fuel cells

NASA Astrophysics Data System (ADS)

Kim, Jinyong; Luo, Gang; Wang, Chao-Yang

2017-10-01

3D fine-mesh flow-fields recently developed by Toyota Mirai improved water management and mass transport in proton exchange membrane (PEM) fuel cell stacks, suggesting their potential value for robust and high-power PEM fuel cell stack performance. In such complex flow-fields, Forchheimer's inertial effect is dominant at high current density. In this work, a two-phase flow model of 3D complex flow-fields of PEMFCs is developed by accounting for Forchheimer's inertial effect, for the first time, to elucidate the underlying mechanism of liquid water behavior and mass transport inside 3D complex flow-fields and their adjacent gas diffusion layers (GDL). It is found that Forchheimer's inertial effect enhances liquid water removal from flow-fields and adds additional flow resistance around baffles, which improves interfacial liquid water and mass transport. As a result, substantial improvements in high current density cell performance and operational stability are expected in PEMFCs with 3D complex flow-fields, compared to PEMFCs with conventional flow-fields. Higher current density operation required to further reduce PEMFC stack cost per kW in the future will necessitate optimizing complex flow-field designs using the present model, in order to efficiently remove a large amount of product water and hence minimize the mass transport voltage loss.

Type 2 Diabetes Genetic Predisposition, Obesity, and All-Cause Mortality Risk in the U.S.: A Multiethnic Analysis

PubMed Central

Leong, Aaron; Porneala, Bianca; Dupuis, Josée; Florez, Jose C.

2016-01-01

OBJECTIVE Type 2 diabetes (T2D) is associated with increased mortality in ethnically diverse populations, although the extent to which this association is genetically determined is unknown. We sought to determine whether T2D-related genetic variants predicted all-cause mortality, even after accounting for BMI, in the Third National Health and Nutrition Examination Survey. RESEARCH DESIGN AND METHODS We modeled mortality risk using a genetic risk score (GRS) from a weighted sum of risk alleles at 38 T2D-related single nucleotide polymorphisms. In age-, sex-, and BMI-adjusted logistic regression models, accounting for the complex survey design, we tested the association with mortality in 6,501 participants. We repeated the analysis within ethnicities (2,528 non-Hispanic white [NHW], 1,979 non-Hispanic black [NHB], and 1,994 Mexican American [MA]) and within BMI categories (<25, 25–30, and ≥30 kg/m2). Significance was set at P < 0.05. RESULTS Over 17 years, 1,556 participants died. GRS was associated with mortality risk (OR 1.04 [95% CI 1.00–1.07] per T2D-associated risk allele, P = 0.05). Within ethnicities, GRS was positively associated with mortality risk in NHW and NHB, but not in MA (0.95 [0.90–1.01], P = 0.07). The negative trend in MA was largely driven by those with BMI <25 kg/m2 (0.91 [0.82–1.00]). In NHW, the positive association was strongest among those with BMI ≥30 kg/m2 (1.07 [1.02–1.12]). CONCLUSIONS In the U.S., a higher T2D genetic risk was associated with increased mortality risk, especially among obese NHW. The underlying genetic basis for mortality likely involves complex interactions with factors related to ethnicity, T2D, and body weight. PMID:26884474

Empirical modeling ENSO dynamics with complex-valued artificial neural networks

NASA Astrophysics Data System (ADS)

Seleznev, Aleksei; Gavrilov, Andrey; Mukhin, Dmitry

2016-04-01

The main difficulty in empirical reconstructing the distributed dynamical systems (e.g. regional climate systems, such as El-Nino-Southern Oscillation - ENSO) is a huge amount of observational data comprising time-varying spatial fields of several variables. An efficient reduction of system's dimensionality thereby is essential for inferring an evolution operator (EO) for a low-dimensional subsystem that determines the key properties of the observed dynamics. In this work, to efficient reduction of observational data sets we use complex-valued (Hilbert) empirical orthogonal functions which are appropriate, by their nature, for describing propagating structures unlike traditional empirical orthogonal functions. For the approximation of the EO, a universal model in the form of complex-valued artificial neural network is suggested. The effectiveness of this approach is demonstrated by predicting both the Jin-Neelin-Ghil ENSO model [1] behavior and real ENSO variability from sea surface temperature anomalies data [2]. The study is supported by Government of Russian Federation (agreement #14.Z50.31.0033 with the Institute of Applied Physics of RAS). 1. Jin, F.-F., J. D. Neelin, and M. Ghil, 1996: El Ni˜no/Southern Oscillation and the annual cycle: subharmonic frequency locking and aperiodicity. Physica D, 98, 442-465. 2. http://iridl.ldeo.columbia.edu/SOURCES/.KAPLAN/.EXTENDED/.v2/.ssta/

3D Printing Based on Cardiac CT Assists Anatomic Visualization Prior to Transcatheter Aortic Valve Replacement

PubMed Central

Ripley, Beth; Kelil, Tatiana; Cheezum, Michael K.; Goncalves, Alexandra; Di Carli, Marcelo F.; Rybicki, Frank J.; Steigner, Mike; Mitsouras, Dimitrios; Blankstein, Ron

2017-01-01

Background 3D printing is a promising technique that may have applications in medicine, and there is expanding interest in the use of patient-specific 3D models to guide surgical interventions. Objective To determine the feasibility of using cardiac CT to print individual models of the aortic root complex for transcatheter aortic valve replacement (TAVR) planning as well as to determine the ability to predict paravalvular aortic regurgitation (PAR). Methods This retrospective study included 16 patients (9 with PAR identified on blinded interpretation of post-procedure trans-thoracic echocardiography and 7 age, sex, and valve size-matched controls with no PAR). 3D printed models of the aortic root were created from pre-TAVR cardiac computed tomography data. These models were fitted with printed valves and predictions regarding post-implant PAR were made using a light transmission test. Results Aortic root 3D models were highly accurate, with excellent agreement between annulus measurements made on 3D models and those made on corresponding 2D data (mean difference of −0.34 mm, 95% limits of agreement: ± 1.3 mm). The 3D printed valve models were within 0.1 mm of their designed dimensions. Examination of the fit of valves within patient-specific aortic root models correctly predicted PAR in 6 of 9 patients (6 true positive, 3 false negative) and absence of PAR in 5 of 7 patients (5 true negative, 2 false positive). Conclusions Pre-TAVR 3D-printing based on cardiac CT provides a unique patient-specific method to assess the physical interplay of the aortic root and implanted valves. With additional optimization, 3D models may complement traditional techniques used for predicting which patients are more likely to develop PAR. PMID:26732862

Recent advances in 3D printing of biomaterials.

PubMed

Chia, Helena N; Wu, Benjamin M

2015-01-01

3D Printing promises to produce complex biomedical devices according to computer design using patient-specific anatomical data. Since its initial use as pre-surgical visualization models and tooling molds, 3D Printing has slowly evolved to create one-of-a-kind devices, implants, scaffolds for tissue engineering, diagnostic platforms, and drug delivery systems. Fueled by the recent explosion in public interest and access to affordable printers, there is renewed interest to combine stem cells with custom 3D scaffolds for personalized regenerative medicine. Before 3D Printing can be used routinely for the regeneration of complex tissues (e.g. bone, cartilage, muscles, vessels, nerves in the craniomaxillofacial complex), and complex organs with intricate 3D microarchitecture (e.g. liver, lymphoid organs), several technological limitations must be addressed. In this review, the major materials and technology advances within the last five years for each of the common 3D Printing technologies (Three Dimensional Printing, Fused Deposition Modeling, Selective Laser Sintering, Stereolithography, and 3D Plotting/Direct-Write/Bioprinting) are described. Examples are highlighted to illustrate progress of each technology in tissue engineering, and key limitations are identified to motivate future research and advance this fascinating field of advanced manufacturing.

Linear and nonlinear equivalent circuit modeling of CMUTs.

PubMed

Lohfink, Annette; Eccardt, Peter-Christian

2005-12-01

Using piston radiator and plate capacitance theory capacitive micromachined ultrasound transducers (CMUT) membrane cells can be described by one-dimensional (1-D) model parameters. This paper describes in detail a new method, which derives a 1-D model for CMUT arrays from finite-element methods (FEM) simulations. A few static and harmonic FEM analyses of a single CMUT membrane cell are sufficient to derive the mechanical and electrical parameters of an equivalent piston as the moving part of the cell area. For an array of parallel-driven cells, the acoustic parameters are derived as a complex mechanical fluid impedance, depending on the membrane shape form. As a main advantage, the nonlinear behavior of the CMUT can be investigated much easier and faster compared to FEM simulations, e.g., for a design of the maximum applicable voltage depending on the input signal. The 1-D parameter model allows an easy description of the CMUT behavior in air and fluids and simplifies the investigation of wave propagation within the connecting fluid represented by FEM or transmission line matrix (TLM) models.

Towards a Quantitative Understanding of Single-Gene Transcription

NASA Astrophysics Data System (ADS)

O'Maoiléidigh, Dáibhid

2008-03-01

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

Assembly and property research on seven 0D–3D complexes derived from imidazole dicarboxylate and 1,2-bi(pyridin-4-yl)ethene

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

Mu, Bao; Li, Qian; Lv, Lei

2015-03-15

The hydrothermal reaction of transition metals, 1H-imidazole-4,5-dicarboxylic acid (H{sub 3}ImDC) and 1,2-bi(pyridin-4-yl)ethene (bpe) affords a series of new complexes, namely, [Mn(HImDC)(bpe)(H{sub 2}O)] (1), [M(H{sub 2}ImDC){sub 2}(H{sub 2}O){sub 2}]·(bpe) (M=Fe(2), Co(3), Zn(4), Cd(6)), [Zn{sub 3}(ImDC){sub 2}(bpe)(H{sub 2}O)]·3H{sub 2}O (5) and [Cd(H{sub 2}ImDC)(bpe)] (7), which are characterized by elemental analyses, IR, TG, XRPD and single crystal X-ray diffraction. Complex 1 exhibits a one dimensional (1D) zigzag chain with two types of irregular rings, and the 1D chains are linked to form a three dimensional (3D) supramolecular framework by the hydrogen bonding interactions (O–H∙∙∙O and O–H∙∙∙N). Complexes 2–4 and 6 are isomorphous, andmore » they display the mononuclear structures. In these complexes, the O–H∙∙∙O and O–H∙∙∙N hydrogen bonds play an important role in sustaining the whole 3D supramolecular frameworks. Complex 5 shows a (3,3)-connected 3D framework with (10{sup 3}) topology, and the lattice water molecules as guest molecules exist in the 3D framework. Complex 7 is a wave-like two dimensional (2D) structure, in which the adjacent 1D chains point at the opposite directions. Moreover, the fluorescent properties of complexes 1–7 and the magnetic property of 1 have been investigated. The water vapor adsorption for complex 5 has been researched at 298 K. - Graphical abstract: Seven new complexes based on different structural characteristics have been hydrothermally synthesized by the mixed ligands. The fluorescent properties, the magnetic property and the water vapor adsorption have been investigated. - Highlights: • The semi-rigid ligand with C=C bonds and imidazole dicarboxylates with some advantages have been used. • A series of new complexes with different structural characteristics have been discussed in detail. • The fluorescent properties, the magnetic property and the water vapor adsorption have been investigated.« less

Verification of the karst flow model under laboratory controlled conditions

NASA Astrophysics Data System (ADS)

Gotovac, Hrvoje; Andric, Ivo; Malenica, Luka; Srzic, Veljko

2016-04-01

Karst aquifers are very important groundwater resources around the world as well as in coastal part of Croatia. They consist of extremely complex structure defining by slow and laminar porous medium and small fissures and usually fast turbulent conduits/karst channels. Except simple lumped hydrological models that ignore high karst heterogeneity, full hydraulic (distributive) models have been developed exclusively by conventional finite element and finite volume elements considering complete karst heterogeneity structure that improves our understanding of complex processes in karst. Groundwater flow modeling in complex karst aquifers are faced by many difficulties such as a lack of heterogeneity knowledge (especially conduits), resolution of different spatial/temporal scales, connectivity between matrix and conduits, setting of appropriate boundary conditions and many others. Particular problem of karst flow modeling is verification of distributive models under real aquifer conditions due to lack of above-mentioned information. Therefore, we will show here possibility to verify karst flow models under the laboratory controlled conditions. Special 3-D karst flow model (5.6*2.6*2 m) consists of concrete construction, rainfall platform, 74 piezometers, 2 reservoirs and other supply equipment. Model is filled by fine sand (3-D porous matrix) and drainage plastic pipes (1-D conduits). This model enables knowledge of full heterogeneity structure including position of different sand layers as well as conduits location and geometry. Moreover, we know geometry of conduits perforation that enable analysis of interaction between matrix and conduits. In addition, pressure and precipitation distribution and discharge flow rates from both phases can be measured very accurately. These possibilities are not present in real sites what this model makes much more useful for karst flow modeling. Many experiments were performed under different controlled conditions such as different levels in left and right end of reservoirs (boundary conditions), different flow regimes in conduits, flow with and without precipitation, free and pressurized discharge from conduits or influence of epikarst (top layer) on recession period. Experimental results are verified by conventional karst flow model (such as MODFLOW-CFP) showing that hydraulic (distributive) models can describe complex behavior of karst flow processes if substantial amount of input data are known from site investigations and monitoring. These results enable us to develop more advanced karst flow models that will improve understanding and analysis of complex flow processes in the real karst aquifers.

Interactions between HIV-1 Reverse Transcriptase and the Downstream Template Strand in Stable Complexes with Primer-Template

PubMed Central

Rutvisuttinunt, Wiriya; Meyer, Peter R.; Scott, Walter A.

2008-01-01

Background Human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) forms stable ternary complexes in which RT is bound tightly at fixed positions on the primer-template (P/T). We have probed downstream interactions between RT and the template strand in the complex containing the incoming dNTP (+1 dNTP•RT•P/T complex) and in the complex containing the pyrophosphate analog, foscarnet (foscarnet•RT•P/T complex). Methods and Results UV-induced cross-linking between RT and the DNA template strand was most efficient when a bromodeoxyuridine residue was placed in the +2 position (the first template position downstream from the incoming dNTP). Furthermore, formation of the +1 dNTP•RT•P/T complex on a biotin-containing template inhibited binding of streptavidin when biotin was in the +2 position on the template but not when the biotin was in the +3 position. Streptavidin pre-bound to a biotin residue in the template caused RT to stall two to three nucleotides upstream from the biotin residue. The downstream border of the complex formed by the stalled RT was mapped by digestion with exonuclease RecJF. UV-induced cross-linking of the complex formed by the pyrophosphate analog, foscarnet, with RT and P/T occurred preferentially with bromodeoxyuridine in the +1 position on the template in keeping with the location of RT one base upstream in the foscarnet•RT•P/T complex (i.e., in the pre-translocation position). Conclusions For +1 dNTP•RT•P/T and foscarnet•RT•P/T stable complexes, tight interactions were observed between RT and the first unpaired template nucleotide following the bound dNTP or the primer terminus, respectively. PMID:18974785

Treacher Collins syndrome mutations in Saccharomyces cerevisiae destabilize RNA polymerase I and III complex integrity.

PubMed

Walker-Kopp, Nancy; Jackobel, Ashleigh J; Pannafino, Gianno N; Morocho, Paola A; Xu, Xia; Knutson, Bruce A

2017-11-01

Treacher Collins syndrome (TCS) is a craniofacial disorder that is characterized by the malformation of the facial bones. Mutations in three genes (TCOF1, POLR1C and POLR1D) involved in RNA polymerase I (Pol I) transcription account for more than 90% of disease cases. Two of these TCS-associated genes, POLR1C and POLR1D, encode for essential Pol I/III subunits that form a heterodimer necessary for Pol I/III assembly, and many TCS mutations lie along their evolutionarily conserved dimerization interface. Here we elucidate the molecular basis of TCS mutations in Saccharomyces cerevisiae, and present a new model for how TCS mutations may disrupt Pol I and III complex integrity. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A multiscale analysis of coral reef topographic complexity using lidar-derived bathymetry

USGS Publications Warehouse

Zawada, D.G.; Brock, J.C.

2009-01-01

Coral reefs represent one of the most irregular substrates in the marine environment. This roughness or topographic complexity is an important structural characteristic of reef habitats that affects a number of ecological and environmental attributes, including species diversity and water circulation. Little is known about the range of topographic complexity exhibited within a reef or between different reef systems. The objective of this study was to quantify topographic complexity for a 5-km x 5-km reefscape along the northern Florida Keys reef tract, over spatial scales ranging from meters to hundreds of meters. The underlying dataset was a 1-m spatial resolution, digital elevation model constructed from lidar measurements. Topographic complexity was quantified using a fractal algorithm, which provided a multi-scale characterization of reef roughness. The computed fractal dimensions (D) are a measure of substrate irregularity and are bounded between values of 2 and 3. Spatial patterns in D were positively correlated with known reef zonation in the area. Landward regions of the study site contain relatively smooth (D ??? 2.35) flat-topped patch reefs, which give way to rougher (D ??? 2.5), deep, knoll-shaped patch reefs. The seaward boundary contains a mixture of substrate features, including discontinuous shelf-edge reefs, and exhibits a corresponding range of roughness values (2.28 ??? D ??? 2.61). ?? 2009 Coastal Education and Research Foundation.

Effect of Low-Dose Ferrous Sulfate vs Iron Polysaccharide Complex on Hemoglobin Concentration in Young Children With Nutritional Iron-Deficiency Anemia: A Randomized Clinical Trial.

PubMed

Powers, Jacquelyn M; Buchanan, George R; Adix, Leah; Zhang, Song; Gao, Ang; McCavit, Timothy L

2017-06-13

Iron-deficiency anemia (IDA) affects millions of persons worldwide, and is associated with impaired neurodevelopment in infants and children. Ferrous sulfate is the most commonly prescribed oral iron despite iron polysaccharide complex possibly being better tolerated. To compare the effect of ferrous sulfate with iron polysaccharide complex on hemoglobin concentration in infants and children with nutritional IDA. Double-blind, superiority randomized clinical trial of infants and children aged 9 to 48 months with nutritional IDA (assessed by history and laboratory criteria) that was conducted in an outpatient hematology clinic at a US tertiary care hospital from September 2013 through November 2015; 12-week follow-up ended in January 2016. Three mg/kg of elemental iron once daily as either ferrous sulfate drops or iron polysaccharide complex drops for 12 weeks. Primary outcome was change in hemoglobin over 12 weeks. Secondary outcomes included complete resolution of IDA (defined as hemoglobin concentration >11 g/dL, mean corpuscular volume >70 fL, reticulocyte hemoglobin equivalent >25 pg, serum ferritin level >15 ng/mL, and total iron-binding capacity <425 μg/dL at the 12-week visit), changes in serum ferritin level and total iron-binding capacity, adverse effects. Of 80 randomized infants and children (median age, 22 months; 55% male; 61% Hispanic white; 40 per group), 59 completed the trial (28 [70%] in ferrous sulfate group; 31 [78%] in iron polysaccharide complex group). From baseline to 12 weeks, mean hemoglobin increased from 7.9 to 11.9 g/dL (ferrous sulfate group) vs 7.7 to 11.1 g/dL (iron complex group), a greater difference of 1.0 g/dL (95% CI, 0.4 to 1.6 g/dL; P < .001) with ferrous sulfate (based on a linear mixed model). Proportion with a complete resolution of IDA was higher in the ferrous sulfate group (29% vs 6%; P = .04). Median serum ferritin level increased from 3.0 to 15.6 ng/mL (ferrous sulfate) vs 2.0 to 7.5 ng/mL (iron complex) over 12 weeks, a greater difference of 10.2 ng/mL (95% CI, 6.2 to 14.1 ng/mL; P < .001) with ferrous sulfate. Mean total iron-binding capacity decreased from 501 to 389 μg/dL (ferrous sulfate) vs 506 to 417 μg/dL (iron complex) (a greater difference of -50 μg/dL [95% CI, -86 to -14 μg/dL] with ferrous sulfate; P < .001). There were more reports of diarrhea in the iron complex group than in the ferrous sulfate group (58% vs 35%, respectively; P = .04). Among infants and children aged 9 to 48 months with nutritional iron-deficiency anemia, ferrous sulfate compared with iron polysaccharide complex resulted in a greater increase in hemoglobin concentration at 12 weeks. Once daily, low-dose ferrous sulfate should be considered for children with nutritional iron-deficiency anemia. clinicaltrials.gov Identifier: NCT01904864.

Quantifying the added value of convection-permitting climate simulations in complex terrain: a systematic evaluation of WRF over the Himalayas

NASA Astrophysics Data System (ADS)

Karki, Ramchandra; Hasson, Shabeh ul; Gerlitz, Lars; Schickhoff, Udo; Scholten, Thomas; Böhner, Jürgen

2017-07-01

Mesoscale dynamical refinements of global climate models or atmospheric reanalysis have shown their potential to resolve intricate atmospheric processes, their land surface interactions, and subsequently, realistic distribution of climatic fields in complex terrains. Given that such potential is yet to be explored within the central Himalayan region of Nepal, we investigate the skill of the Weather Research and Forecasting (WRF) model with different spatial resolutions in reproducing the spatial, seasonal, and diurnal characteristics of the near-surface air temperature and precipitation as well as the spatial shifts in the diurnal monsoonal precipitation peak over the Khumbu (Everest), Rolwaling, and adjacent southern areas. Therefore, the ERA-Interim (0.75°) reanalysis has been dynamically refined to 25, 5, and 1 km (D1, D2, and D3) for one complete hydrological year (October 2014-September 2015), using the one-way nested WRF model run with mild nudging and parameterized convection for the outer but explicitly resolved convection for the inner domains. Our results suggest that D3 realistically reproduces the monsoonal precipitation, as compared to its underestimation by D1 but overestimation by D2. All three resolutions, however, overestimate precipitation from the westerly disturbances, owing to simulating anomalously higher intensity of few intermittent events. Temperatures are generally reproduced well by all resolutions; however, winter and pre-monsoon seasons feature a high cold bias for high elevations while lower elevations show a simultaneous warm bias. Unlike higher resolutions, D1 fails to realistically reproduce the regional-scale nocturnal monsoonal peak precipitation observed in the Himalayan foothills and its diurnal shift towards high elevations, whereas D2 resolves these characteristics but exhibits a limited skill in reproducing such a peak on the river valley scale due to the limited representation of the narrow valleys at 5 km resolution. Nonetheless, featuring a substantial skill over D1 and D2, D3 simulates almost realistic shapes of the seasonal and diurnal precipitation and the peak timings even on valley scales. These findings clearly suggest an added value of the convective-scale resolutions in realistically resolving the topoclimates over the central Himalayas, which in turn allows simulating their interactions with the synoptic-scale weather systems prevailing over high Asia.

A Multi-Dimensional Heat Transfer Model of a Tie-Tube and Hexagonal Fuel Element for Nuclear Thermal Propulsion

NASA Technical Reports Server (NTRS)

Gomez, C. F.; Mireles, O. R.; Stewart, E.

2016-01-01

The Space Capable Cryogenic Thermal Engine (SCCTE) effort considers a nuclear thermal rocket design based around a Low-Enriched Uranium (LEU) design fission reactor. The reactor core is comprised of bundled hexagonal fuel elements that directly heat hydrogen for expansion in a thrust chamber and hexagonal tie-tubes that house zirconium hydride moderator mass for the purpose of thermalizing fast neutrons resulting from fission events. Created 3D steady state Hex fuel rod model with 1D flow channels. Hand Calculation were used to set up initial conditions for fluid flow. The Hex Fuel rod uses 1D flow paths to model the channels using empirical correlations for heat transfer in a pipe. Created a 2-D axisymmetric transient to steady state model using the CFD turbulent flow and Heat Transfer module in COMSOL. This model was developed to find and understand the hydrogen flow that might effect the thermal gradients axially and at the end of the tie tube where the flow turns and enters an annulus. The Hex fuel rod and Tie tube models were made based on requirements given to us by CSNR and the SCCTE team. The models helped simplify and understand the physics and assumptions. Using pipe correlations reduced the complexity of the 3-D fuel rod model and is numerically more stable and computationally more time-efficient compared to the CFD approach. The 2-D axisymmetric tie tube model can be used as a reference "Virtual test model" for comparing and improving 3-D Models.

New metal-organic complexes based on bis(tetrazole) ligands: Synthesis, structures and properties

NASA Astrophysics Data System (ADS)

Du, Ceng-Ceng; Fan, Jian-Zhong; Wang, Xin-Fang; Zhou, Sheng-Bin; Wang, Duo-Zhi

2017-04-01

In this paper, a series of new complexes, [Zn2(HL1)2(H2O)4]·H2O (1), [Co2(HL1)2]·TEA (2), [Co3(HL1)2(H2L1)2(H2O)4]n (3), [Cu(HL1)(H2O)2]n (4), {[Cu5(HL2)2(OH)4(ClO4)2]·4H2O}n (5) and [Cu2(L3)]n (6) were successfully prepared by utilizing three bis(tetrazole) ligands [bis-(1H-tetrazol-5-ylmethyl)-amine (H3L1), bis-(1H-tetrazol-5-ylethyl)-amine (H3L2) and 1,5-bis(5-tetrazolo)-3-thiapentane (H2L3)], all of which have been characterized by elemental analyses, FT-IR spectroscopy, powder X-ray diffraction (PXRD), thermogravimetric analyses as well as single-crystal X-ray diffraction analyses showing different dimensionalities (0D, 1D and 3D). Complexes 1 and 2 are 0D structures, 1 shows a dinuclear structure, 2 displays two crystallographically different mononuclear structures, 1 and 2 are further assembled to form 3D supramolecular framework and 2D supramolecular network by hydrogen-bonding interactions, respectively. Complexes 3, 4 and 5 are 1D structures, 3 features a mononuclear unit and a 1D chain, which are arranged into 3D supramolecular architecture by hydrogen-bonding interactions, 4 presents a zigzag chain, 5 shows an infinite chain structure constructed from pentanuclear Cu(II) subunits and ClO4- anions. Complex 6 exhibits a 3D coordination framework based on cyclic [Cu4(L3)2] dimmer subunits as nodes possessing an 8-connected network topology with the point symbol {424·64}. Further, semiconductor behaviors, the solid-state luminescent properties of the complexes 1-3 and 6 were measured and studied seriously at room temperature.

Integrating structure-from-motion photogrammetry with geospatial software as a novel technique for quantifying 3D ecological characteristics of coral reefs

PubMed Central

Delparte, D; Gates, RD; Takabayashi, M

2015-01-01

The structural complexity of coral reefs plays a major role in the biodiversity, productivity, and overall functionality of reef ecosystems. Conventional metrics with 2-dimensional properties are inadequate for characterization of reef structural complexity. A 3-dimensional (3D) approach can better quantify topography, rugosity and other structural characteristics that play an important role in the ecology of coral reef communities. Structure-from-Motion (SfM) is an emerging low-cost photogrammetric method for high-resolution 3D topographic reconstruction. This study utilized SfM 3D reconstruction software tools to create textured mesh models of a reef at French Frigate Shoals, an atoll in the Northwestern Hawaiian Islands. The reconstructed orthophoto and digital elevation model were then integrated with geospatial software in order to quantify metrics pertaining to 3D complexity. The resulting data provided high-resolution physical properties of coral colonies that were then combined with live cover to accurately characterize the reef as a living structure. The 3D reconstruction of reef structure and complexity can be integrated with other physiological and ecological parameters in future research to develop reliable ecosystem models and improve capacity to monitor changes in the health and function of coral reef ecosystems. PMID:26207190

Autoinhibition of Munc18-1 modulates synaptobrevin binding and helps to enable Munc13-dependent regulation of membrane fusion.

PubMed

Sitarska, Ewa; Xu, Junjie; Park, Seungmee; Liu, Xiaoxia; Quade, Bradley; Stepien, Karolina; Sugita, Kyoko; Brautigam, Chad A; Sugita, Shuzo; Rizo, Josep

2017-05-06

Munc18-1 orchestrates SNARE complex assembly together with Munc13-1 to mediate neurotransmitter release. Munc18-1 binds to synaptobrevin, but the relevance of this interaction and its relation to Munc13 function are unclear. NMR experiments now show that Munc18-1 binds specifically and non-specifically to synaptobrevin. Specific binding is inhibited by a L348R mutation in Munc18-1 and enhanced by a D326K mutation designed to disrupt the 'furled conformation' of a Munc18-1 loop. Correspondingly, the activity of Munc18-1 in reconstitution assays that require Munc18-1 and Munc13-1 for membrane fusion is stimulated by the D326K mutation and inhibited by the L348R mutation. Moreover, the D326K mutation allows Munc13-1-independent fusion and leads to a gain-of-function in rescue experiments in Caenorhabditis elegans unc-18 nulls. Together with previous studies, our data support a model whereby Munc18-1 acts as a template for SNARE complex assembly, and autoinhibition of synaptobrevin binding contributes to enabling regulation of neurotransmitter release by Munc13-1.

Exploring the Impact of Visual Complexity Levels in 3d City Models on the Accuracy of Individuals' Orientation and Cognitive Maps

NASA Astrophysics Data System (ADS)

Rautenbach, V.; Çöltekin, A.; Coetzee, S.

2015-08-01

In this paper we report results from a qualitative user experiment (n=107) designed to contribute to understanding the impact of various levels of complexity (mainly based on levels of detail, i.e., LoD) in 3D city models, specifically on the participants' orientation and cognitive (mental) maps. The experiment consisted of a number of tasks motivated by spatial cognition theory where participants (among other things) were given orientation tasks, and in one case also produced sketches of a path they `travelled' in a virtual environment. The experiments were conducted in groups, where individuals provided responses on an answer sheet. The preliminary results based on descriptive statistics and qualitative sketch analyses suggest that very little information (i.e., a low LoD model of a smaller area) might have a negative impact on the accuracy of cognitive maps constructed based on a virtual experience. Building an accurate cognitive map is an inherently desired effect of the visualizations in planning tasks, thus the findings are important for understanding how to develop better-suited 3D visualizations such as 3D city models. In this study, we specifically discuss the suitability of different levels of visual complexity for development planning (urban planning), one of the domains where 3D city models are most relevant.

Using Geometry-Based Metrics as Part of Fitness-for-Purpose Evaluations of 3D City Models

NASA Astrophysics Data System (ADS)

Wong, K.; Ellul, C.

2016-10-01

Three-dimensional geospatial information is being increasingly used in a range of tasks beyond visualisation. 3D datasets, however, are often being produced without exact specifications and at mixed levels of geometric complexity. This leads to variations within the models' geometric and semantic complexity as well as the degree of deviation from the corresponding real world objects. Existing descriptors and measures of 3D data such as CityGML's level of detail are perhaps only partially sufficient in communicating data quality and fitness-for-purpose. This study investigates whether alternative, automated, geometry-based metrics describing the variation of complexity within 3D datasets could provide additional relevant information as part of a process of fitness-for-purpose evaluation. The metrics include: mean vertex/edge/face counts per building; vertex/face ratio; minimum 2D footprint area and; minimum feature length. Each metric was tested on six 3D city models from international locations. The results show that geometry-based metrics can provide additional information on 3D city models as part of fitness-for-purpose evaluations. The metrics, while they cannot be used in isolation, may provide a complement to enhance existing data descriptors if backed up with local knowledge, where possible.

Age-related changes in mitochondrial antioxidant enzyme Trx2 and TXNIP-Trx2-ASK1 signal pathways in the auditory cortex of a mimetic aging rat model: changes to Trx2 in the auditory cortex.

PubMed

Sun, Hai-Ying; Hu, Yu-Juan; Zhao, Xue-Yan; Zhong, Yi; Zeng, Ling-Ling; Chen, Xu-Bo; Yuan, Jie; Wu, Jing; Sun, Yu; Kong, Wen; Kong, Wei-Jia

2015-07-01

Age-associated degeneration in the central auditory system, which is defined as central presbycusis, can impair sound localization and speech perception. Research has shown that oxidative stress plays a central role in the pathological process of central presbycusis. Thioredoxin 2 (Trx2), one member of thioredoxin family, plays a key role in regulating the homeostasis of cellular reactive oxygen species and anti-apoptosis. The purpose of this study was to explore the association between Trx2 and the phenotype of central presbycusis using a mimetic aging animal model induced by long-term exposure to d-galactose (d-Gal). We also explored changes in thioredoxin-interacting protein (TXNIP), apoptosis signal regulating kinase 1 (ASK1) and phosphorylated ASK1 (p-ASK1) expression, as well as the Trx2-TXNIP/Trx2-ASK1 binding complex in the auditory cortex of mimetic aging rats. Our results demonstrate that, compared with control groups, the levels of Trx2 and Trx2-ASK1 binding complex were significantly reduced, whereas TXNIP, ASK1 p-ASK1 expression, and Trx2-TXNIP binding complex were significantly increased in the auditory cortex of the mimetic aging groups. Our results indicated that changes in Trx2 and the TXNIP-Trx2-ASK1 signal pathway may participate in the pathogenesis of central presbycusis. © 2015 FEBS.

Residence time of symmetric random walkers in a strip with large reflective obstacles

NASA Astrophysics Data System (ADS)

Ciallella, Alessandro; Cirillo, Emilio N. M.; Sohier, Julien

2018-05-01

We study the effect of a large obstacle on the so-called residence time, i.e., the time that a particle performing a symmetric random walk in a rectangular (two-dimensional, 2D) domain needs to cross the strip. We observe complex behavior: We find out that the residence time does not depend monotonically on the geometric properties of the obstacle, such as its width, length, and position. In some cases, due to the presence of the obstacle, the mean residence time is shorter with respect to the one measured for the obstacle-free strip. We explain the residence time behavior by developing a one-dimensional (1D) analog of the 2D model where the role of the obstacle is played by two defect sites having smaller probability to be crossed with respect to all the other regular sites. The 1D and 2D models behave similarly, but in the 1D case we are able to compute exactly the residence time, finding a perfect match with the Monte Carlo simulations.

Quantifying Complexity in Quantum Phase Transitions via Mutual Information Complex Networks

NASA Astrophysics Data System (ADS)

Valdez, Marc Andrew; Jaschke, Daniel; Vargas, David L.; Carr, Lincoln D.

2017-12-01

We quantify the emergent complexity of quantum states near quantum critical points on regular 1D lattices, via complex network measures based on quantum mutual information as the adjacency matrix, in direct analogy to quantifying the complexity of electroencephalogram or functional magnetic resonance imaging measurements of the brain. Using matrix product state methods, we show that network density, clustering, disparity, and Pearson's correlation obtain the critical point for both quantum Ising and Bose-Hubbard models to a high degree of accuracy in finite-size scaling for three classes of quantum phase transitions, Z2, mean field superfluid to Mott insulator, and a Berzinskii-Kosterlitz-Thouless crossover.

Predicting a double mutant in the twilight zone of low homology modeling for the skeletal muscle voltage-gated sodium channel subunit beta-1 (Nav1.4 β1)

PubMed Central

Scior, Thomas; Paiz-Candia, Bertin; Islas, Ángel A.; Sánchez-Solano, Alfredo; Millan-Perez Peña, Lourdes; Mancilla-Simbro, Claudia; Salinas-Stefanon, Eduardo M.

2015-01-01

The molecular structure modeling of the β1 subunit of the skeletal muscle voltage-gated sodium channel (Nav1.4) was carried out in the twilight zone of very low homology. Structural significance can per se be confounded with random sequence similarities. Hence, we combined (i) not automated computational modeling of weakly homologous 3D templates, some with interfaces to analogous structures to the pore-bearing Nav1.4 α subunit with (ii) site-directed mutagenesis (SDM), as well as (iii) electrophysiological experiments to study the structure and function of the β1 subunit. Despite the distant phylogenic relationships, we found a 3D-template to identify two adjacent amino acids leading to the long-awaited loss of function (inactivation) of Nav1.4 channels. This mutant type (T109A, N110A, herein called TANA) was expressed and tested on cells of hamster ovary (CHO). The present electrophysiological results showed that the double alanine substitution TANA disrupted channel inactivation as if the β1 subunit would not be in complex with the α subunit. Exhaustive and unbiased sampling of “all β proteins” (Ig-like, Ig) resulted in a plethora of 3D templates which were compared to the target secondary structure prediction. The location of TANA was made possible thanks to another “all β protein” structure in complex with an irreversible bound protein as well as a reversible protein–protein interface (our “Rosetta Stone” effect). This finding coincides with our electrophysiological data (disrupted β1-like voltage dependence) and it is safe to utter that the Nav1.4 α/β1 interface is likely to be of reversible nature. PMID:25904995

Predicting a double mutant in the twilight zone of low homology modeling for the skeletal muscle voltage-gated sodium channel subunit beta-1 (Nav1.4 β1).

PubMed

Scior, Thomas; Paiz-Candia, Bertin; Islas, Ángel A; Sánchez-Solano, Alfredo; Millan-Perez Peña, Lourdes; Mancilla-Simbro, Claudia; Salinas-Stefanon, Eduardo M

2015-01-01

The molecular structure modeling of the β1 subunit of the skeletal muscle voltage-gated sodium channel (Nav1.4) was carried out in the twilight zone of very low homology. Structural significance can per se be confounded with random sequence similarities. Hence, we combined (i) not automated computational modeling of weakly homologous 3D templates, some with interfaces to analogous structures to the pore-bearing Nav1.4 α subunit with (ii) site-directed mutagenesis (SDM), as well as (iii) electrophysiological experiments to study the structure and function of the β1 subunit. Despite the distant phylogenic relationships, we found a 3D-template to identify two adjacent amino acids leading to the long-awaited loss of function (inactivation) of Nav1.4 channels. This mutant type (T109A, N110A, herein called TANA) was expressed and tested on cells of hamster ovary (CHO). The present electrophysiological results showed that the double alanine substitution TANA disrupted channel inactivation as if the β1 subunit would not be in complex with the α subunit. Exhaustive and unbiased sampling of "all β proteins" (Ig-like, Ig) resulted in a plethora of 3D templates which were compared to the target secondary structure prediction. The location of TANA was made possible thanks to another "all β protein" structure in complex with an irreversible bound protein as well as a reversible protein-protein interface (our "Rosetta Stone" effect). This finding coincides with our electrophysiological data (disrupted β1-like voltage dependence) and it is safe to utter that the Nav1.4 α/β1 interface is likely to be of reversible nature.

Structural model of the hUbA1-UbcH10 quaternary complex: in silico and experimental analysis of the protein-protein interactions between E1, E2 and ubiquitin.

PubMed

Correale, Stefania; de Paola, Ivan; Morgillo, Carmine Marco; Federico, Antonella; Zaccaro, Laura; Pallante, Pierlorenzo; Galeone, Aldo; Fusco, Alfredo; Pedone, Emilia; Luque, F Javier; Catalanotti, Bruno

2014-01-01

UbcH10 is a component of the Ubiquitin Conjugation Enzymes (Ubc; E2) involved in the ubiquitination cascade controlling the cell cycle progression, whereby ubiquitin, activated by E1, is transferred through E2 to the target protein with the involvement of E3 enzymes. In this work we propose the first three dimensional model of the tetrameric complex formed by the human UbA1 (E1), two ubiquitin molecules and UbcH10 (E2), leading to the transthiolation reaction. The 3D model was built up by using an experimentally guided incremental docking strategy that combined homology modeling, protein-protein docking and refinement by means of molecular dynamics simulations. The structural features of the in silico model allowed us to identify the regions that mediate the recognition between the interacting proteins, revealing the active role of the ubiquitin crosslinked to E1 in the complex formation. Finally, the role of these regions involved in the E1-E2 binding was validated by designing short peptides that specifically interfere with the binding of UbcH10, thus supporting the reliability of the proposed model and representing valuable scaffolds for the design of peptidomimetic compounds that can bind selectively to Ubcs and inhibit the ubiquitylation process in pathological disorders.

Interpreting three-dimensional structures from two-dimensional images: a web-based interactive 3D teaching model of surgical liver anatomy

PubMed Central

Crossingham, Jodi L; Jenkinson, Jodie; Woolridge, Nick; Gallinger, Steven; Tait, Gordon A; Moulton, Carol-Anne E

2009-01-01

Background: Given the increasing number of indications for liver surgery and the growing complexity of operations, many trainees in surgical, imaging and related subspecialties require a good working knowledge of the complex intrahepatic anatomy. Computed tomography (CT), the most commonly used liver imaging modality, enhances our understanding of liver anatomy, but comprises a two-dimensional (2D) representation of a complex 3D organ. It is challenging for trainees to acquire the necessary skills for converting these 2D images into 3D mental reconstructions because learning opportunities are limited and internal hepatic anatomy is complicated, asymmetrical and variable. We have created a website that uses interactive 3D models of the liver to assist trainees in understanding the complex spatial anatomy of the liver and to help them create a 3D mental interpretation of this anatomy when viewing CT scans. Methods: Computed tomography scans were imported into DICOM imaging software (OsiriX™) to obtain 3D surface renderings of the liver and its internal structures. Using these 3D renderings as a reference, 3D models of the liver surface and the intrahepatic structures, portal veins, hepatic veins, hepatic arteries and the biliary system were created using 3D modelling software (Cinema 4D™). Results: Using current best practices for creating multimedia tools, a unique, freely available, online learning resource has been developed, entitled Visual Interactive Resource for Teaching, Understanding And Learning Liver Anatomy (VIRTUAL Liver) (http://pie.med.utoronto.ca/VLiver). This website uses interactive 3D models to provide trainees with a constructive resource for learning common liver anatomy and liver segmentation, and facilitates the development of the skills required to mentally reconstruct a 3D version of this anatomy from 2D CT scans. Discussion: Although the intended audience for VIRTUAL Liver consists of residents in various medical and surgical specialties, the website will also be useful for other health care professionals (i.e. radiologists, nurses, hepatologists, radiation oncologists, family doctors) and educators because it provides a comprehensive resource for teaching liver anatomy. PMID:19816618

Model reduction of the numerical analysis of Low Impact Developments techniques

NASA Astrophysics Data System (ADS)

Brunetti, Giuseppe; Šimůnek, Jirka; Wöhling, Thomas; Piro, Patrizia

2017-04-01

Mechanistic models have proven to be accurate and reliable tools for the numerical analysis of the hydrological behavior of Low Impact Development (LIDs) techniques. However, their widespread adoption is limited by their complexity and computational cost. Recent studies have tried to address this issue by investigating the application of new techniques, such as surrogate-based modeling. However, current results are still limited and fragmented. One of such approaches, the Model Order Reduction (MOR) technique, can represent a valuable tool for reducing the computational complexity of a numerical problems by computing an approximation of the original model. While this technique has been extensively used in water-related problems, no studies have evaluated its use in LIDs modeling. Thus, the main aim of this study is to apply the MOR technique for the development of a reduced order model (ROM) for the numerical analysis of the hydrologic behavior of LIDs, in particular green roofs. The model should be able to correctly reproduce all the hydrological processes of a green roof while reducing the computational cost. The proposed model decouples the subsurface water dynamic of a green roof in a) one-dimensional (1D) vertical flow through a green roof itself and b) one-dimensional saturated lateral flow along the impervious rooftop. The green roof is horizontally discretized in N elements. Each element represents a vertical domain, which can have different properties or boundary conditions. The 1D Richards equation is used to simulate flow in the substrate and drainage layers. Simulated outflow from the vertical domain is used as a recharge term for saturated lateral flow, which is described using the kinematic wave approximation of the Boussinesq equation. The proposed model has been compared with the mechanistic model HYDRUS-2D, which numerically solves the Richards equation for the whole domain. The HYDRUS-1D code has been used for the description of vertical flow, while a Finite Volume Scheme has been adopted for lateral flow. Two scenarios involving flat and steep green roofs were analyzed. Results confirmed the accuracy of the reduced order model, which was able to reproduce both subsurface outflow and the moisture distribution in the green roof, significantly reducing the computational cost.

Structural Insights into HIV Reverse Transcriptase Mutations Q151M and Q151M Complex That Confer Multinucleoside Drug Resistance

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

Das, Kalyan; Martinez, Sergio E.; Arnold, Eddy

HIV-1 reverse transcriptase (RT) is targeted by multiple drugs. RT mutations that confer resistance to nucleoside RT inhibitors (NRTIs) emerge during clinical use. Q151M and four associated mutations, A62V, V75I, F77L, and F116Y, were detected in patients failing therapies with dideoxynucleosides (didanosine [ddI], zalcitabine [ddC]) and/or zidovudine (AZT). The cluster of the five mutations is referred to as the Q151M complex (Q151Mc), and an RT or virus containing Q151Mc exhibits resistance to multiple NRTIs. To understand the structural basis for Q151M and Q151Mc resistance, we systematically determined the crystal structures of the wild-type RT/double-stranded DNA (dsDNA)/dATP (complex I), wild-type RT/dsDNA/ddATPmore » (complex II), Q151M RT/dsDNA/dATP (complex III), Q151Mc RT/dsDNA/dATP (complex IV), and Q151Mc RT/dsDNA/ddATP (complex V) ternary complexes. The structures revealed that the deoxyribose rings of dATP and ddATP have 3'-endo and 3'-exo conformations, respectively. The single mutation Q151M introduces conformational perturbation at the deoxynucleoside triphosphate (dNTP)-binding pocket, and the mutated pocket may exist in multiple conformations. The compensatory set of mutations in Q151Mc, particularly F116Y, restricts the side chain flexibility of M151 and helps restore the DNA polymerization efficiency of the enzyme. The altered dNTP-binding pocket in Q151Mc RT has the Q151-R72 hydrogen bond removed and has a switched conformation for the key conserved residue R72 compared to that in wild-type RT. On the basis of a modeled structure of hepatitis B virus (HBV) polymerase, the residues R72, Y116, M151, and M184 in Q151Mc HIV-1 RT are conserved in wild-type HBV polymerase as residues R41, Y89, M171, and M204, respectively; functionally, both Q151Mc HIV-1 and wild-type HBV are resistant to dideoxynucleoside analogs.« less

3D MHD Modeling of Prominence Formation by Plasma Evaporation and Condensation

NASA Astrophysics Data System (ADS)

Torok, T.; Lionello, R.; Mikic, Z.; Downs, C.; Titov, V. S.

2017-12-01

The formation of prominence material in the solar corona still belongs to the open questions of solar physics. There exists a consensus that prominence plasma has to be of chromospheric origin, but the mechanisms by which it accumulates in the corona are still not well understood. The presently most accepted scenario invokes the evaporation of chromospheric plasma via foot point heating and its subsequent condensation in the corona via thermal instabilities. This scenario has been successfully modeled in 1D hydrodynamic simulations along single field lines of a static magnetic field, but a more appropriate, fully 3D treatment of the thermodynamics in time-dependent magnetic fields was started just very recently by Xia et al. Our group at PSI has recently begun to engage in this challenging task as well, using our time-dependent, fully 3D thermodynamic MHD code MAS. For our investigation we consider two different coronal flux-rope configurations, using the analytical model by Titov and Démoulin and a model in which an elongated flux rope is constructed by photospheric flows. We investigate the plasma behavior for both configurations, using heating models of different complexity, and accompany our analysis by 1D loop simulations performed along selected field lines. In this presentation, we outline our modeling approach and discuss the results obtained so far.

Dynamic effects of root system architecture improve root water uptake in 1-D process-based soil-root hydrodynamics

NASA Astrophysics Data System (ADS)

Bouda, Martin; Saiers, James E.

2017-12-01

Root system architecture (RSA) can significantly affect plant access to water, total transpiration, as well as its partitioning by soil depth, with implications for surface heat, water, and carbon budgets. Despite recent advances in land surface model (LSM) descriptions of plant hydraulics, descriptions of RSA have not been included because of their three-dimensional complexity, which makes them generally too computationally costly. Here we demonstrate a new, process-based 1D layered model that captures the dynamic shifts in water potential gradients of 3D RSA under different soil moisture conditions: the RSA stencil. Using root systems calibrated to the rooting profiles of four plant functional types (PFT) of the Community Land Model, we show that the RSA stencil predicts plant water potentials within 2% to the outputs of a full 3D model, under the same assumptions on soil moisture heterogeneity, despite its trivial computational cost, resulting in improved predictions of water uptake and soil moisture compared to a model without RSA in a transient simulation. Our results suggest that LSM predictions of soil moisture dynamics and dependent variables can be improved by the implementation of this model, calibrated for individual PFTs using field observations.

Investigation of unsteadiness in Shock-particle cloud interaction: Fully resolved two-dimensional simulation and one-dimensional modeling

NASA Astrophysics Data System (ADS)

Hosseinzadeh-Nik, Zahra; Regele, Jonathan D.

2015-11-01

Dense compressible particle-laden flow, which has a complex nature, exists in various engineering applications. Shock waves impacting a particle cloud is a canonical problem to investigate this type of flow. It has been demonstrated that large flow unsteadiness is generated inside the particle cloud from the flow induced by the shock passage. It is desirable to develop models for the Reynolds stress to capture the energy contained in vortical structures so that volume-averaged models with point particles can be simulated accurately. However, the previous work used Euler equations, which makes the prediction of vorticity generation and propagation innacurate. In this work, a fully resolved two dimensional (2D) simulation using the compressible Navier-Stokes equations with a volume penalization method to model the particles has been performed with the parallel adaptive wavelet-collocation method. The results still show large unsteadiness inside and downstream of the particle cloud. A 1D model is created for the unclosed terms based upon these 2D results. The 1D model uses a two-phase simple low dissipation AUSM scheme (TSLAU) developed by coupled with the compressible two phase kinetic energy equation.

Computational 3D structures of drug-targeting proteins in the 2009-H1N1 influenza A virus

NASA Astrophysics Data System (ADS)

Du, Qi-Shi; Wang, Shu-Qing; Huang, Ri-Bo; Chou, Kuo-Chen

2010-01-01

The neuraminidase (NA) and M2 proton channel of influenza virus are the drug-targeting proteins, based on which several drugs were developed. However these once powerful drugs encountered drug-resistant problem to the H5N1 and H1N1 flu. To address this problem, the computational 3D structures of NA and M2 proteins of 2009-H1N1 influenza virus were built using the molecular modeling technique and computational chemistry method. Based on the models the structure features of NA and M2 proteins were analyzed, the docking structures of drug-protein complexes were computed, and the residue mutations were annotated. The results may help to solve the drug-resistant problem and stimulate designing more effective drugs against 2009-H1N1 influenza pandemic.

Simulating Scenario Floods for Hazard Assessment on the Lower Bicol Floodplain, the Philippines

NASA Astrophysics Data System (ADS)

Usamah, Muhibuddin Bin; Alkema, Dinand

This paper describes the first results from a study to the behavior of floods in the lower Bicol area, the Philippines. A 1D2D dynamic hydraulic model was applied to simulate a set of scenario floods through the complex topography of the city Naga and surrounding area. The simulation results are integrated into a multi-parameter hazard zonation for the five scenario floods.

The Complex-Step-Finite-Difference method

NASA Astrophysics Data System (ADS)

Abreu, Rafael; Stich, Daniel; Morales, Jose

2015-07-01

We introduce the Complex-Step-Finite-Difference method (CSFDM) as a generalization of the well-known Finite-Difference method (FDM) for solving the acoustic and elastic wave equations. We have found a direct relationship between modelling the second-order wave equation by the FDM and the first-order wave equation by the CSFDM in 1-D, 2-D and 3-D acoustic media. We present the numerical methodology in order to apply the introduced CSFDM and show an example for wave propagation in simple homogeneous and heterogeneous models. The CSFDM may be implemented as an extension into pre-existing numerical techniques in order to obtain fourth- or sixth-order accurate results with compact three time-level stencils. We compare advantages of imposing various types of initial motion conditions of the CSFDM and demonstrate its higher-order accuracy under the same computational cost and dispersion-dissipation properties. The introduced method can be naturally extended to solve different partial differential equations arising in other fields of science and engineering.

Relating the ac complex resistivity of the pinned vortex lattice to its shear modulus

NASA Astrophysics Data System (ADS)

Ong, N. P.; Wu, Hui

1997-07-01

We propose a way to determine the shear rigidity of the pinned vortex lattice in high-purity crystals from the dependence of its complex resistivity ρ⁁ on frequency (ω). The lattice is modeled as an elastic medium pinned by a sparse, random distribution of defects. We relate ρ⁁ to the velocity of the small subset of pinned vortices via the lattice propagator G(R,ω). Measuring ρ⁁ versus ω is equivalent to determining G(R,ω) versus R. The range of G(R,ω) depends sensitively on the shear and tilt moduli. We describe the evaluation of G(R,ω) in two-dimensional (2D) and 3D lattices. The 2D analysis provides a close fit to the frequency dependence of Reρ⁁ measured in an untwinned crystal of YBa2Cu3O7 at 89 K in a field of 0.5 and 1.0 T. We compare our results with earlier models.

Spectroscopic ellipsometric studies of the dielectric function of Cd1-x-yMnxFeyTe single crystals

NASA Astrophysics Data System (ADS)

Hwang, Younghun; Kim, Hyekyeong; Um, Youngho; Park, Hyoyeol

2004-06-01

Cd1-x-yMnxFeyTe single crystals grown by the vertical Bridgman method have been studied by measuring the complex dielectric function using spectroscopic ellipsometry in the 1.5 5.5 eV photon energy range at room temperature. The CP energy parameters of the E0, E1, E1 + 1, and E2 structures were determined by fitting the second-derivative spectra (d2/d2) with a theoretical model, i.e., the standard critical point (SCP) line shapes. The E1, E1 + 1, and E2 energies decreased with increasing Fe composition y, which is due to the hybridization effect of the valence and conduction bands in Cd1-xMnxTe with Fe 3d levels.

A 3D human neural cell culture system for modeling Alzheimer’s disease

PubMed Central

Kim, Young Hye; Choi, Se Hoon; D’Avanzo, Carla; Hebisch, Matthias; Sliwinski, Christopher; Bylykbashi, Enjana; Washicosky, Kevin J.; Klee, Justin B.; Brüstle, Oliver; Tanzi, Rudolph E.; Kim, Doo Yeon

2015-01-01

Stem cell technologies have facilitated the development of human cellular disease models that can be used to study pathogenesis and test therapeutic candidates. These models hold promise for complex neurological diseases such as Alzheimer’s disease (AD) because existing animal models have been unable to fully recapitulate all aspects of pathology. We recently reported the characterization of a novel three-dimensional (3D) culture system that exhibits key events in AD pathogenesis, including extracellular aggregation of β-amyloid and accumulation of hyperphosphorylated tau. Here we provide instructions for the generation and analysis of 3D human neural cell cultures, including the production of genetically modified human neural progenitor cells (hNPCs) with familial AD mutations, the differentiation of the hNPCs in a 3D matrix, and the analysis of AD pathogenesis. The 3D culture generation takes 1–2 days. The aggregation of β-amyloid is observed after 6-weeks of differentiation followed by robust tau pathology after 10–14 weeks. PMID:26068894

On the validity of travel-time based nonlinear bioreactive transport models in steady-state flow.

PubMed

Sanz-Prat, Alicia; Lu, Chuanhe; Finkel, Michael; Cirpka, Olaf A

2015-01-01

Travel-time based models simplify the description of reactive transport by replacing the spatial coordinates with the groundwater travel time, posing a quasi one-dimensional (1-D) problem and potentially rendering the determination of multidimensional parameter fields unnecessary. While the approach is exact for strictly advective transport in steady-state flow if the reactive properties of the porous medium are uniform, its validity is unclear when local-scale mixing affects the reactive behavior. We compare a two-dimensional (2-D), spatially explicit, bioreactive, advective-dispersive transport model, considered as "virtual truth", with three 1-D travel-time based models which differ in the conceptualization of longitudinal dispersion: (i) neglecting dispersive mixing altogether, (ii) introducing a local-scale longitudinal dispersivity constant in time and space, and (iii) using an effective longitudinal dispersivity that increases linearly with distance. The reactive system considers biodegradation of dissolved organic carbon, which is introduced into a hydraulically heterogeneous domain together with oxygen and nitrate. Aerobic and denitrifying bacteria use the energy of the microbial transformations for growth. We analyze six scenarios differing in the variance of log-hydraulic conductivity and in the inflow boundary conditions (constant versus time-varying concentration). The concentrations of the 1-D models are mapped to the 2-D domain by means of the kinematic (for case i), and mean groundwater age (for cases ii & iii), respectively. The comparison between concentrations of the "virtual truth" and the 1-D approaches indicates extremely good agreement when using an effective, linearly increasing longitudinal dispersivity in the majority of the scenarios, while the other two 1-D approaches reproduce at least the concentration tendencies well. At late times, all 1-D models give valid approximations of two-dimensional transport. We conclude that the conceptualization of nonlinear bioreactive transport in complex multidimensional domains by quasi 1-D travel-time models is valid for steady-state flow fields if the reactants are introduced over a wide cross-section, flow is at quasi steady state, and dispersive mixing is adequately parametrized. Copyright © 2015 Elsevier B.V. All rights reserved.

Biallelic Mutations in ATP5F1D , which Encodes a Subunit of ATP Synthase, Cause a Metabolic Disorder

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

Oláhová, Monika; Yoon, Wan Hee; Thompson, Kyle

ATP synthase, H + transporting, mitochondrial F1 complex, δ subunit (ATP5F1D; formerly ATP5D) is a subunit of mitochondrial ATP synthase and plays an important role in coupling proton translocation and ATP production. Here, we describe two individuals, each with homozygous missense variants in ATP5F1D, who presented with episodic lethargy, metabolic acidosis, 3-methylglutaconic aciduria, and hyperammonemia. Subject 1, homozygous for c.245C>T (p.Pro82Leu), presented with recurrent metabolic decompensation starting in the neonatal period, and subject 2, homozygous for c.317T>G (p.Val106Gly), presented with acute encephalopathy in childhood. Cultured skin fibroblasts from these individuals exhibited impaired assembly of F 1F O ATP synthase andmore » subsequent reduced complex V activity. Cells from subject 1 also exhibited a significant decrease in mitochondrial cristae. Knockdown of Drosophila ATPsynδ, the ATP5F1D homolog, in developing eyes and brains caused a near complete loss of the fly head, a phenotype that was fully rescued by wild-type human ATP5F1D. In contrast, expression of the ATP5F1D c.245C>T and c.317T>G variants rescued the head-size phenotype but recapitulated the eye and antennae defects seen in other genetic models of mitochondrial oxidative phosphorylation deficiency. Our data establish c.245C>T (p.Pro82Leu) and c.317T>G (p.Val106Gly) in ATP5F1D as pathogenic variants leading to a Mendelian mitochondrial disease featuring episodic metabolic decompensation.« less

Biallelic Mutations in ATP5F1D, which Encodes a Subunit of ATP Synthase, Cause a Metabolic Disorder.

PubMed

Oláhová, Monika; Yoon, Wan Hee; Thompson, Kyle; Jangam, Sharayu; Fernandez, Liliana; Davidson, Jean M; Kyle, Jennifer E; Grove, Megan E; Fisk, Dianna G; Kohler, Jennefer N; Holmes, Matthew; Dries, Annika M; Huang, Yong; Zhao, Chunli; Contrepois, Kévin; Zappala, Zachary; Frésard, Laure; Waggott, Daryl; Zink, Erika M; Kim, Young-Mo; Heyman, Heino M; Stratton, Kelly G; Webb-Robertson, Bobbie-Jo M; Snyder, Michael; Merker, Jason D; Montgomery, Stephen B; Fisher, Paul G; Feichtinger, René G; Mayr, Johannes A; Hall, Julie; Barbosa, Ines A; Simpson, Michael A; Deshpande, Charu; Waters, Katrina M; Koeller, David M; Metz, Thomas O; Morris, Andrew A; Schelley, Susan; Cowan, Tina; Friederich, Marisa W; McFarland, Robert; Van Hove, Johan L K; Enns, Gregory M; Yamamoto, Shinya; Ashley, Euan A; Wangler, Michael F; Taylor, Robert W; Bellen, Hugo J; Bernstein, Jonathan A; Wheeler, Matthew T

2018-03-01

ATP synthase, H + transporting, mitochondrial F1 complex, δ subunit (ATP5F1D; formerly ATP5D) is a subunit of mitochondrial ATP synthase and plays an important role in coupling proton translocation and ATP production. Here, we describe two individuals, each with homozygous missense variants in ATP5F1D, who presented with episodic lethargy, metabolic acidosis, 3-methylglutaconic aciduria, and hyperammonemia. Subject 1, homozygous for c.245C>T (p.Pro82Leu), presented with recurrent metabolic decompensation starting in the neonatal period, and subject 2, homozygous for c.317T>G (p.Val106Gly), presented with acute encephalopathy in childhood. Cultured skin fibroblasts from these individuals exhibited impaired assembly of F 1 F O ATP synthase and subsequent reduced complex V activity. Cells from subject 1 also exhibited a significant decrease in mitochondrial cristae. Knockdown of Drosophila ATPsynδ, the ATP5F1D homolog, in developing eyes and brains caused a near complete loss of the fly head, a phenotype that was fully rescued by wild-type human ATP5F1D. In contrast, expression of the ATP5F1D c.245C>T and c.317T>G variants rescued the head-size phenotype but recapitulated the eye and antennae defects seen in other genetic models of mitochondrial oxidative phosphorylation deficiency. Our data establish c.245C>T (p.Pro82Leu) and c.317T>G (p.Val106Gly) in ATP5F1D as pathogenic variants leading to a Mendelian mitochondrial disease featuring episodic metabolic decompensation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Biallelic Mutations in ATP5F1D , which Encodes a Subunit of ATP Synthase, Cause a Metabolic Disorder

DOE PAGES

Oláhová, Monika; Yoon, Wan Hee; Thompson, Kyle; ...

2018-02-22

ATP synthase, H + transporting, mitochondrial F1 complex, δ subunit (ATP5F1D; formerly ATP5D) is a subunit of mitochondrial ATP synthase and plays an important role in coupling proton translocation and ATP production. Here, we describe two individuals, each with homozygous missense variants in ATP5F1D, who presented with episodic lethargy, metabolic acidosis, 3-methylglutaconic aciduria, and hyperammonemia. Subject 1, homozygous for c.245C>T (p.Pro82Leu), presented with recurrent metabolic decompensation starting in the neonatal period, and subject 2, homozygous for c.317T>G (p.Val106Gly), presented with acute encephalopathy in childhood. Cultured skin fibroblasts from these individuals exhibited impaired assembly of F 1F O ATP synthase andmore » subsequent reduced complex V activity. Cells from subject 1 also exhibited a significant decrease in mitochondrial cristae. Knockdown of Drosophila ATPsynδ, the ATP5F1D homolog, in developing eyes and brains caused a near complete loss of the fly head, a phenotype that was fully rescued by wild-type human ATP5F1D. In contrast, expression of the ATP5F1D c.245C>T and c.317T>G variants rescued the head-size phenotype but recapitulated the eye and antennae defects seen in other genetic models of mitochondrial oxidative phosphorylation deficiency. Our data establish c.245C>T (p.Pro82Leu) and c.317T>G (p.Val106Gly) in ATP5F1D as pathogenic variants leading to a Mendelian mitochondrial disease featuring episodic metabolic decompensation.« less

A Prototype Digital Library for 3D Collections: Tools To Capture, Model, Analyze, and Query Complex 3D Data.

ERIC Educational Resources Information Center

Rowe, Jeremy; Razdan, Anshuman

The Partnership for Research in Spatial Modeling (PRISM) project at Arizona State University (ASU) developed modeling and analytic tools to respond to the limitations of two-dimensional (2D) data representations perceived by affiliated discipline scientists, and to take advantage of the enhanced capabilities of three-dimensional (3D) data that…

A MAPK-Driven Feedback Loop Suppresses Rac Activity to Promote RhoA-Driven Cancer Cell Invasion

PubMed Central

Hetmanski, Joseph H. R.; Zindy, Egor; Schwartz, Jean-Marc; Caswell, Patrick T.

2016-01-01

Cell migration in 3D microenvironments is fundamental to development, homeostasis and the pathobiology of diseases such as cancer. Rab-coupling protein (RCP) dependent co-trafficking of α5β1 and EGFR1 promotes cancer cell invasion into fibronectin (FN) containing extracellular matrix (ECM), by potentiating EGFR1 signalling at the front of invasive cells. This promotes a switch in RhoGTPase signalling to inhibit Rac1 and activate a RhoA-ROCK-Formin homology domain-containing 3 (FHOD3) pathway and generate filopodial actin-spike protrusions which drive invasion. To further understand the signalling network that drives RCP-driven invasive migration, we generated a Boolean logical model based on existing network pathways/models, where each node can be interrogated by computational simulation. The model predicted an unanticipated feedback loop, whereby Raf/MEK/ERK signalling maintains suppression of Rac1 by inhibiting the Rac-activating Sos1-Eps8-Abi1 complex, allowing RhoA activity to predominate in invasive protrusions. MEK inhibition was sufficient to promote lamellipodia formation and oppose filopodial actin-spike formation, and led to activation of Rac and inactivation of RhoA at the leading edge of cells moving in 3D matrix. Furthermore, MEK inhibition abrogated RCP/α5β1/EGFR1-driven invasive migration. However, upon knockdown of Eps8 (to suppress the Sos1-Abi1-Eps8 complex), MEK inhibition had no effect on RhoGTPase activity and did not oppose invasive migration, suggesting that MEK-ERK signalling suppresses the Rac-activating Sos1-Abi1-Eps8 complex to maintain RhoA activity and promote filopodial actin-spike formation and invasive migration. Our study highlights the predictive potential of mathematical modelling approaches, and demonstrates that a simple intervention (MEK-inhibition) could be of therapeutic benefit in preventing invasive migration and metastasis. PMID:27138333

Bioprinting the Cancer Microenvironment.

PubMed

Zhang, Yu Shrike; Duchamp, Margaux; Oklu, Rahmi; Ellisen, Leif W; Langer, Robert; Khademhosseini, Ali

2016-10-10

Cancer is intrinsically complex, comprising both heterogeneous cellular compositions and microenvironmental cues. During the various stages of cancer initiation, development, and metastasis, cell-cell interactions (involving vascular and immune cells besides cancerous cells) as well as cell-extracellular matrix (ECM) interactions (e.g., alteration in stiffness and composition of the surrounding matrix) play major roles. Conventional cancer models both two- and three-dimensional (2D and 3D) present numerous limitations as they lack good vascularization and cannot mimic the complexity of tumors, thereby restricting their use as biomimetic models for applications such as drug screening and fundamental cancer biology studies. Bioprinting as an emerging biofabrication platform enables the creation of high-resolution 3D structures and has been extensively used in the past decade to model multiple organs and diseases. More recently, this versatile technique has further found its application in studying cancer genesis, growth, metastasis, and drug responses through creation of accurate models that recreate the complexity of the cancer microenvironment. In this review we will focus first on cancer biology and limitations with current cancer models. We then detail the current bioprinting strategies including the selection of bioinks for capturing the properties of the tumor matrices, after which we discuss bioprinting of vascular structures that are critical toward construction of complex 3D cancer organoids. We finally conclude with current literature on bioprinted cancer models and propose future perspectives.

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.

Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling

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

Lin, Su-Chang; Lo, Yu-Chih; Wu, Hao

2010-08-23

MyD88, IRAK4 and IRAK2 are critical signalling mediators of the TLR/IL1-R superfamily. Here we report the crystal structure of the MyD88-IRAK4-IRAK2 death domain (DD) complex, which surprisingly reveals a left-handed helical oligomer that consists of 6 MyD88, 4 IRAK4 and 4 IRAK2 DDs. Assembly of this helical signalling tower is hierarchical, in which MyD88 recruits IRAK4 and the MyD88-IRAK4 complex recruits the IRAK4 substrates IRAK2 or the related IRAK1. Formation of these Myddosome complexes brings the kinase domains of IRAKs into proximity for phosphorylation and activation. Composite binding sites are required for recruitment of the individual DDs in the complex,more » which are confirmed by mutagenesis and previously identified signalling mutations. Specificities in Myddosome formation are dictated by both molecular complementarity and correspondence of surface electrostatics. The MyD88-IRAK4-IRAK2 complex provides a template for Toll signalling in Drosophila and an elegant mechanism for versatile assembly and regulation of DD complexes in signal transduction.« less

Assembly of oligomeric death domain complexes during Toll receptor signaling.

PubMed

Moncrieffe, Martin C; Grossmann, J Günter; Gay, Nicholas J

2008-11-28

The Drosophila Toll receptor is activated by the endogenous protein ligand Spätzle in response to microbial stimuli in immunity and spatial cues during embryonic development. Downstream signaling is mediated by the adaptor proteins Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation primary response protein (dMyD88). Here we have characterized heterodimeric (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We show that both the heterodimeric and heterotrimeric complexes form kidney-shaped structures and that Tube is bivalent and has separate high affinity binding sites for dMyD88 and Pelle. Additionally we found no interaction between the isolated death domains of Pelle and dMyD88. These results indicate that the mode of assembly of the heterotrimeric dMyD88-Tube-Pelle complex downstream of the activated Toll receptor is unique. The measured dissociation constants for the interaction between the death domains of dMyD88 and Tube and of Pelle and a preformed dMyD88-Tube complex are used to propose a model of the early postreceptor events in Drosophila Toll receptor signaling.

Assembly of Oligomeric Death Domain Complexes during Toll Receptor Signaling*

PubMed Central

Moncrieffe, Martin C.; Grossmann, J. Günter; Gay, Nicholas J.

2008-01-01

The Drosophila Toll receptor is activated by the endogenous protein ligand Spätzle in response to microbial stimuli in immunity and spatial cues during embryonic development. Downstream signaling is mediated by the adaptor proteins Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation primary response protein (dMyD88). Here we have characterized heterodimeric (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We show that both the heterodimeric and heterotrimeric complexes form kidney-shaped structures and that Tube is bivalent and has separate high affinity binding sites for dMyD88 and Pelle. Additionally we found no interaction between the isolated death domains of Pelle and dMyD88. These results indicate that the mode of assembly of the heterotrimeric dMyD88-Tube-Pelle complex downstream of the activated Toll receptor is unique. The measured dissociation constants for the interaction between the death domains of dMyD88 and Tube and of Pelle and a preformed dMyD88-Tube complex are used to propose a model of the early postreceptor events in Drosophila Toll receptor signaling. PMID:18829464

HFE gene variants modify the association between maternal lead burden and infant birthweight: a prospective birth cohort study in Mexico City, Mexico.

PubMed

Cantonwine, David; Hu, Howard; Téllez-Rojo, Martha Maria; Sánchez, Brisa N; Lamadrid-Figueroa, Héctor; Ettinger, Adrienne S; Mercado-García, Adriana; Hernández-Avila, Mauricio; Wright, Robert O

2010-07-26

Neonatal growth is a complex process involving genetic and environmental factors. Polymorphisms in the hemochromatosis (HFE) iron regulatory genes have been shown to modify transport and toxicity of lead which is known to affect birth weight. We investigated the role of HFE C282Y, HFE H63 D, and transferrin (TF) P570 S gene variants in modifying the association of lead and infant birthweight in a cohort of Mexican mother-infant pairs. Subjects were initially recruited between 1994-1995 from three maternity hospitals in Mexico City and 411 infants/565 mothers had archived blood available for genotyping. Multiple linear regression models, stratified by either maternal/infant HFE or TF genotype and then combined with interaction terms, were constructed examining the association of lead and birthweight after controlling for covariates. 3.1%, 16.8% and 17.5% of infants (N=390) and 1.9%, 14.5% and 18.9% of mothers (N=533) carried the HFE C282Y, HFE H63D, and TF P570 S variants, respectively. The presence of infant HFE H63 D variants predicted 110.3 g (95% CI -216.1, -4.6) decreases in birthweight while maternal HFE H63 D variants predicted reductions of 52.0 g (95% CI -147.3 to 43.2). Interaction models suggest that both maternal and infant HFE H63 D genotype may modify tibia lead's effect on infant birthweight in opposing ways. In our interaction models, maternal HFE H63 D variant carriers had a negative association between tibia lead and birthweight. These results suggest that the HFE H63 D genotype modifies lead's effects on infant birthweight in a complex fashion that may reflect maternal-fetal interactions with respect to the metabolism and transport of metals.

A New Low Complexity Angle of Arrival Algorithm for 1D and 2D Direction Estimation in MIMO Smart Antenna Systems

PubMed Central

Al-Sadoon, Mohammed A. G.; Zuid, Abdulkareim; Jones, Stephen M. R.; Noras, James M.

2017-01-01

This paper proposes a new low complexity angle of arrival (AOA) method for signal direction estimation in multi-element smart wireless communication systems. The new method estimates the AOAs of the received signals directly from the received signals with significantly reduced complexity since it does not need to construct the correlation matrix, invert the matrix or apply eigen-decomposition, which are computationally expensive. A mathematical model of the proposed method is illustrated and then verified using extensive computer simulations. Both linear and circular sensors arrays are studied using various numerical examples. The method is systematically compared with other common and recently introduced AOA methods over a wide range of scenarios. The simulated results show that the new method has several advantages in terms of reduced complexity and improved accuracy under the assumptions of correlated signals and limited numbers of snapshots. PMID:29140313

A New Low Complexity Angle of Arrival Algorithm for 1D and 2D Direction Estimation in MIMO Smart Antenna Systems.

PubMed

Al-Sadoon, Mohammed A G; Ali, Nazar T; Dama, Yousf; Zuid, Abdulkareim; Jones, Stephen M R; Abd-Alhameed, Raed A; Noras, James M

2017-11-15

This paper proposes a new low complexity angle of arrival (AOA) method for signal direction estimation in multi-element smart wireless communication systems. The new method estimates the AOAs of the received signals directly from the received signals with significantly reduced complexity since it does not need to construct the correlation matrix, invert the matrix or apply eigen-decomposition, which are computationally expensive. A mathematical model of the proposed method is illustrated and then verified using extensive computer simulations. Both linear and circular sensors arrays are studied using various numerical examples. The method is systematically compared with other common and recently introduced AOA methods over a wide range of scenarios. The simulated results show that the new method has several advantages in terms of reduced complexity and improved accuracy under the assumptions of correlated signals and limited numbers of snapshots.

Collective cell behavior on basement membranes floating in space

NASA Astrophysics Data System (ADS)

Ellison, Sarah; Bhattacharjee, Tapomoy; Morley, Cameron; Sawyer, W.; Angelini, Thomas

The basement membrane is an essential part of the polarity of endothelial and epithelial tissues. In tissue culture and organ-on-chip devices, monolayer polarity can be established by coating flat surfaces with extracellular matrix proteins and tuning the trans-substrate permeability. In epithelial 3D culture, spheroids spontaneously establish inside-out polarity, morphing into hollow shell-like structures called acini, generating their own basement membrane on the inner radius of the shell. However, 3D culture approaches generally lack the high degree of control provided by the 2D culture plate or organ-on-chip devices, making it difficult to create more faithful in vitro tissue models with complex surface curvature and morphology. Here we present a method for 3D printing complex basement membranes covered in cells. We 3D print collagen-I and Matrigel into a 3D growth medium made from jammed microgels. This soft, yielding material allows extracellular matrix to be formed as complex surfaces and shapes, floating in space. We then distribute MCF10A epithelial cells across the polymerized surface. We envision employing this strategy to study 3D collective cell behavior in numerous model tissue layers, beyond this simple epithelial model.

Clinical application of three-dimensional reconstruction and rapid prototyping technology of multislice spiral computed tomography angiography for the repair of ventricular septal defect of tetralogy of Fallot.

PubMed

Ma, X J; Tao, L; Chen, X; Li, W; Peng, Z Y; Chen, Y; Jin, J; Zhang, X L; Xiong, Q F; Zhong, Z L; Chen, X F

2015-02-13

Three-dimensional (3D) reconstruction and rapid prototyping technology (RPT) of multislice spiral computed tomography angiography (CTA) was applied to prepare physical models of the heart and ventricular septal defects of tetralogy of Fallot (ToF) patients in order to explore their applications in the diagnosis and treatment of this complex heart disease. CTA data of 35 ToF patients were collected to prepare l:l 3D solid models using digital 3D reconstruction and RPT, and the resultant models were used intraoperatively as reference. The operations of all 35 patients were completed under the guidance of the 3D solid model, without difficulty. Intraoperative findings of the patients were consistent with the morphological and size changes of the 3D solid model, and no significant differences were found between the patches obtained from the 3D solid model and the actual intraoperative measurements (t = 0.83, P = 0.412). 3D reconstruction and RPT of multislice spiral CTA can accurately and intuitively reflect the anatomy of ventricular septal defects in ToF patients, providing the foundation for a solid model of the complex congenital heart.

Three-dimensional surgical simulation improves the planning for correction of facial prognathism and asymmetry: A qualitative and quantitative study

PubMed Central

Ho, Cheng-Ting; Lin, Hsiu-Hsia; Liou, Eric J. W.; Lo, Lun-Jou

2017-01-01

Traditional planning method for orthognathic surgery has limitations of cephalometric analysis, especially for patients with asymmetry. The aim of this study was to assess surgical plan modification after 3-demensional (3D) simulation. The procedures were to perform traditional surgical planning, construction of 3D model for the initial surgical plan (P1), 3D model of altered surgical plan after simulation (P2), comparison between P1 and P2 models, surgical execution, and postoperative validation using superimposition and root-mean-square difference (RMSD) between postoperative 3D image and P2 simulation model. Surgical plan was modified after 3D simulation in 93% of the cases. Absolute linear changes of landmarks in mediolateral direction (x-axis) were significant and between 1.11 to 1.62 mm. The pitch, yaw, and roll rotation as well as ramus inclination correction also showed significant changes after the 3D planning. Yaw rotation of the maxillomandibular complex (1.88 ± 0.32°) and change of ramus inclination (3.37 ± 3.21°) were most frequently performed for correction of the facial asymmetry. Errors between the postsurgical image and 3D simulation were acceptable, with RMSD 0.63 ± 0.25 mm for the maxilla and 0.85 ± 0.41 mm for the mandible. The information from this study could be used to augment the clinical planning and surgical execution when a conventional approach is applied. PMID:28071714

Modeling and inversion Matlab algorithms for resistivity, induced polarization and seismic data

NASA Astrophysics Data System (ADS)

Karaoulis, M.; Revil, A.; Minsley, B. J.; Werkema, D. D.

2011-12-01

M. Karaoulis (1), D.D. Werkema (3), A. Revil (1,2), A., B. Minsley (4), (1) Colorado School of Mines, Dept. of Geophysics, Golden, CO, USA. (2) ISTerre, CNRS, UMR 5559, Université de Savoie, Equipe Volcan, Le Bourget du Lac, France. (3) U.S. EPA, ORD, NERL, ESD, CMB, Las Vegas, Nevada, USA . (4) USGS, Federal Center, Lakewood, 10, 80225-0046, CO. Abstract We propose 2D and 3D forward modeling and inversion package for DC resistivity, time domain induced polarization (IP), frequency-domain IP, and seismic refraction data. For the resistivity and IP case, discretization is based on rectangular cells, where each cell has as unknown resistivity in the case of DC modelling, resistivity and chargeability in the time domain IP modelling, and complex resistivity in the spectral IP modelling. The governing partial-differential equations are solved with the finite element method, which can be applied to both real and complex variables that are solved for. For the seismic case, forward modeling is based on solving the eikonal equation using a second-order fast marching method. The wavepaths are materialized by Fresnel volumes rather than by conventional rays. This approach accounts for complicated velocity models and is advantageous because it considers frequency effects on the velocity resolution. The inversion can accommodate data at a single time step, or as a time-lapse dataset if the geophysical data are gathered for monitoring purposes. The aim of time-lapse inversion is to find the change in the velocities or resistivities of each model cell as a function of time. Different time-lapse algorithms can be applied such as independent inversion, difference inversion, 4D inversion, and 4D active time constraint inversion. The forward algorithms are benchmarked against analytical solutions and inversion results are compared with existing ones. The algorithms are packaged as Matlab codes with a simple Graphical User Interface. Although the code is parallelized for multi-core cpus, it is not as fast as machine code. In the case of large datasets, someone should consider transferring parts of the code to C or Fortran through mex files. This code is available through EPA's website on the following link http://www.epa.gov/esd/cmb/GeophysicsWebsite/index.html Although this work was reviewed by EPA and approved for publication, it may not necessarily reflect official Agency policy.

Multistability with a Metastable Mixed State

NASA Astrophysics Data System (ADS)

Sneppen, Kim; Mitarai, Namiko

2012-09-01

Complex dynamical systems often show multiple metastable states. In macroevolution, such behavior is suggested by punctuated equilibrium and discrete geological epochs. In molecular biology, bistability is found in epigenetics and in the many mutually exclusive states that a human cell can take. Sociopolitical systems can be single-party regimes or a pluralism of balancing political fractions. To introduce multistability, we suggest a model system of D mutually exclusive microstates that battle for dominance in a large system. Assuming one common intermediate state, we obtain D+1 metastable macrostates for the system, one of which is a self-reinforced mixture of all D+1 microstates. Robustness of this metastable mixed state increases with diversity D.

Syntheses, structures and luminescence of three copper(I) cyanide coordination polymers based on trigonal 1,3,5-tris(1H-imidazol-1-yl)benzene ligand

NASA Astrophysics Data System (ADS)

Shao, Min; Li, Ming-Xing; Lu, Li-Ruo; Zhang, Heng-Hua

2016-09-01

Three Cu(I)-cyanide coordination polymers based on trigonal 1,3,5-tris(1H-imidazol-1-yl)benzene (tib) ligand, namely [Cu3(CN)3(tib)]n (1), [Cu4(CN)4(tib)]n (2), and [Cu2(CN)2(tib)]n (3), have been prepared and characterized by elemental analysis, IR, PXRD, thermogravimetry and single-crystal X-ray diffraction analysis. Complex 1 displays a 3D metal-organic framework with nanosized pores. Complex 2 is a 3D coordination polymer assembled by three μ2-cyanides and a μ3-cyanide with a very short Cu(I)···Cu(I) metal bond(2.5206 Å). Complex 3 is a 2D coordination polymer constructing from 1D Cu(I)-cyanide zigzag chain and bidentate tib spacer. Three Cu(I) complexes are thermally stable up to 250-350 °C. Complexes 1-3 show similar orange emission band at 602 nm originating from LMCT mechanism.

Comparison of 3D Echocardiogram-Derived 3D Printed Valve Models to Molded Models for Simulated Repair of Pediatric Atrioventricular Valves.

PubMed

Scanlan, Adam B; Nguyen, Alex V; Ilina, Anna; Lasso, Andras; Cripe, Linnea; Jegatheeswaran, Anusha; Silvestro, Elizabeth; McGowan, Francis X; Mascio, Christopher E; Fuller, Stephanie; Spray, Thomas L; Cohen, Meryl S; Fichtinger, Gabor; Jolley, Matthew A

2018-03-01

Mastering the technical skills required to perform pediatric cardiac valve surgery is challenging in part due to limited opportunity for practice. Transformation of 3D echocardiographic (echo) images of congenitally abnormal heart valves to realistic physical models could allow patient-specific simulation of surgical valve repair. We compared materials, processes, and costs for 3D printing and molding of patient-specific models for visualization and surgical simulation of congenitally abnormal heart valves. Pediatric atrioventricular valves (mitral, tricuspid, and common atrioventricular valve) were modeled from transthoracic 3D echo images using semi-automated methods implemented as custom modules in 3D Slicer. Valve models were then both 3D printed in soft materials and molded in silicone using 3D printed "negative" molds. Using pre-defined assessment criteria, valve models were evaluated by congenital cardiac surgeons to determine suitability for simulation. Surgeon assessment indicated that the molded valves had superior material properties for the purposes of simulation compared to directly printed valves (p < 0.01). Patient-specific, 3D echo-derived molded valves are a step toward realistic simulation of complex valve repairs but require more time and labor to create than directly printed models. Patient-specific simulation of valve repair in children using such models may be useful for surgical training and simulation of complex congenital cases.

A computationally identified compound antagonizes excess FGF-23 signaling in renal tubules and a mouse model of hypophosphatemia

DOE PAGES

Xiao, Zhousheng; Riccardi, Demian; Velazquez, Hector A.; ...

2016-11-22

Fibroblast growth factor–23 (FGF-23) interacts with a binary receptor complex composed of α-Klotho (α-KL) and FGF receptors (FGFRs) to regulate phosphate and vitamin D metabolism in the kidney. Excess FGF-23 production, which causes hypophosphatemia, is genetically inherited or occurs with chronic kidney disease. Among other symptoms, hypophosphatemia causes vitamin D deficiency and the bone-softening disorder rickets. Current therapeutics that target the receptor complex have limited utility clinically. In this paper, using a computationally driven, structure-based, ensemble docking and virtual high-throughput screening approach, we identified four novel compounds predicted to selectively inhibit FGF-23–induced activation of the FGFR/α-KL complex. Additional modeling andmore » functional analysis found that Zinc13407541 bound to FGF-23 and disrupted its interaction with the FGFR1/α-KL complex; experiments in a heterologous cell expression system showed that Zinc13407541 selectivity inhibited α-KL–dependent FGF-23 signaling. Zinc13407541 also inhibited FGF-23 signaling in isolated renal tubules ex vivo and partially reversed the hypophosphatemic effects of excess FGF-23 in a mouse model. Finally, these chemical probes provide a platform to develop lead compounds to treat disorders caused by excess FGF-23.« less

A computationally identified compound antagonizes excess FGF-23 signaling in renal tubules and a mouse model of hypophosphatemia.

PubMed

Xiao, Zhousheng; Riccardi, Demian; Velazquez, Hector A; Chin, Ai L; Yates, Charles R; Carrick, Jesse D; Smith, Jeremy C; Baudry, Jerome; Quarles, L Darryl

2016-11-22

Fibroblast growth factor-23 (FGF-23) interacts with a binary receptor complex composed of α-Klotho (α-KL) and FGF receptors (FGFRs) to regulate phosphate and vitamin D metabolism in the kidney. Excess FGF-23 production, which causes hypophosphatemia, is genetically inherited or occurs with chronic kidney disease. Among other symptoms, hypophosphatemia causes vitamin D deficiency and the bone-softening disorder rickets. Current therapeutics that target the receptor complex have limited utility clinically. Using a computationally driven, structure-based, ensemble docking and virtual high-throughput screening approach, we identified four novel compounds predicted to selectively inhibit FGF-23-induced activation of the FGFR/α-KL complex. Additional modeling and functional analysis found that Zinc13407541 bound to FGF-23 and disrupted its interaction with the FGFR1/α-KL complex; experiments in a heterologous cell expression system showed that Zinc13407541 selectivity inhibited α-KL-dependent FGF-23 signaling. Zinc13407541 also inhibited FGF-23 signaling in isolated renal tubules ex vivo and partially reversed the hypophosphatemic effects of excess FGF-23 in a mouse model. These chemical probes provide a platform to develop lead compounds to treat disorders caused by excess FGF-23. Copyright © 2016, American Association for the Advancement of Science.

A computationally identified compound antagonizes excess FGF-23 signaling in renal tubules and a mouse model of hypophosphatemia

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

Xiao, Zhousheng; Riccardi, Demian; Velazquez, Hector A.

Fibroblast growth factor–23 (FGF-23) interacts with a binary receptor complex composed of α-Klotho (α-KL) and FGF receptors (FGFRs) to regulate phosphate and vitamin D metabolism in the kidney. Excess FGF-23 production, which causes hypophosphatemia, is genetically inherited or occurs with chronic kidney disease. Among other symptoms, hypophosphatemia causes vitamin D deficiency and the bone-softening disorder rickets. Current therapeutics that target the receptor complex have limited utility clinically. In this paper, using a computationally driven, structure-based, ensemble docking and virtual high-throughput screening approach, we identified four novel compounds predicted to selectively inhibit FGF-23–induced activation of the FGFR/α-KL complex. Additional modeling andmore » functional analysis found that Zinc13407541 bound to FGF-23 and disrupted its interaction with the FGFR1/α-KL complex; experiments in a heterologous cell expression system showed that Zinc13407541 selectivity inhibited α-KL–dependent FGF-23 signaling. Zinc13407541 also inhibited FGF-23 signaling in isolated renal tubules ex vivo and partially reversed the hypophosphatemic effects of excess FGF-23 in a mouse model. Finally, these chemical probes provide a platform to develop lead compounds to treat disorders caused by excess FGF-23.« less

Modelling of Tc migration in an un-oxidized fractured drill core from Äspö, Sweden

NASA Astrophysics Data System (ADS)

Huber, F. M.; Totskiy, Y.; Montoya Garcia, V.; Enzmann, F.; Trumm, M.; Wenka, A.; Geckeis, H.; Schaefer, T.

2015-12-01

The radionuclide retention of redox sensitive radionuclides (e.g. Pu, Np, U, Tc) in crystalline host rock greatly depends on the rock matrix and the rock redox capacity. Preservation of drill cores concerning oxidation is therefore of paramount importance to reliably predict the near-natural radionuclide retention properties. Here, experimental results of HTO and Tc laboratory migration experiments in a naturally single fractured Äspö un-oxidized drill core are modelled using two different 2D models. Both models employ geometrical information obtained by μ-computed tomography (μCT) scanning of the drill core. The models differ in geometrical complexity meaning the first model (PPM-MD) consists of a simple parallel plate with a porous matrix adjacent to the fracture whereas the second model (MPM) uses the mid-plane of the 3D fracture only (no porous matrix). Simulation results show that for higher flow rates (Peclet number > 1), the MPM satisfactorily describes the HTO breakthrough curves (BTC) whereas the PPM-MD model nicely reproduces the HTO BTC for small Pe numbers (<1). These findings clearly highlight the influence of fracture geometry/flow field complexity on solute transport for Pe numbers > 1 and the dominating effect of matrix diffusion for Peclet numbers < 1. Retention of Tc is modelled using a simple Kd-approach in case of the PPM-MD and including 1st order sorptive reduction/desorption kinetics in case of the MPM. Batch determined sorptive reduction/desorption kinetic rates and Kd values for Tc on non-oxidized Äspö diorite are used in the model and compared to best fit values. By this approach, the transferability of kinetic data concerning sorptive reduction determined in static batch experiments to dynamic transport experiments is examined.

Hybrid scatterometry measurement for BEOL process control

NASA Astrophysics Data System (ADS)

Timoney, Padraig; Vaid, Alok; Kang, Byeong Cheol; Liu, Haibo; Isbester, Paul; Cheng, Marjorie; Ng-Emans, Susan; Yellai, Naren; Sendelbach, Matt; Koret, Roy; Gedalia, Oram

2017-03-01

Scaling of interconnect design rules in advanced nodes has been accompanied by a reducing metrology budget for BEOL process control. Traditional inline optical metrology measurements of BEOL processes rely on 1-dimensional (1D) film pads to characterize film thickness. Such pads are designed on the assumption that solid copper blocks from previous metallization layers prevent any light from penetrating through the copper, thus simplifying the effective film stack for the 1D optical model. However, the reduction of the copper thickness in each metallization layer and CMP dishing effects within the pad, have introduced undesired noise in the measurement. To resolve this challenge and to measure structures that are more representative of product, scatterometry has been proposed as an alternative measurement. Scatterometry is a diffraction based optical measurement technique using Rigorous Coupled Wave Analysis (RCWA), where light diffracted from a periodic structure is used to characterize the profile. Scatterometry measurements on 3D structures have been shown to demonstrate strong correlation to electrical resistance parameters for BEOL Etch and CMP processes. However, there is significant modeling complexity in such 3D scatterometry models, in particlar due to complexity of front-end-of-line (FEOL) and middle-of-line (MOL) structures. The accompanying measurement noise associated with such structures can contribute significant measurement error. To address the measurement noise of the 3D structures and the impact of incoming process variation, a hybrid scatterometry technique is proposed that utilizes key information from the structure to significantly reduce the measurement uncertainty of the scatterometry measurement. Hybrid metrology combines measurements from two or more metrology techniques to enable or improve the measurement of a critical parameter. In this work, the hybrid scatterometry technique is evaluated for 7nm and 14nm node BEOL measurements of interlayer dielectric (ILD) thickness, hard mask thickness and dielectric trench etch in complex 3D structures. The data obtained from the hybrid scatterometry technique demonstrates stable measurement precision, improved within wafer and wafer to wafer range, robustness in cases where 3D scatterometry measurements incur undesired shifts in the measurements, accuracy as compared to TEM and correlation to process deposition time. Process capability indicator comparisons also demonstrate improvement as compared to conventional scatterometry measurements. The results validate the suitability of the method for monitoring of production BEOL processes.

3D Printing in Surgical Management of Double Outlet Right Ventricle.

PubMed

Yoo, Shi-Joon; van Arsdell, Glen S

2017-01-01

Double outlet right ventricle (DORV) is a heterogeneous group of congenital heart diseases that require individualized surgical approach based on precise understanding of the complex cardiovascular anatomy. Physical 3-dimensional (3D) print models not only allow fast and unequivocal perception of the complex anatomy but also eliminate misunderstanding or miscommunication among imagers and surgeons. Except for those cases showing well-recognized classic surgical anatomy of DORV such as in cases with a typical subaortic or subpulmonary ventricular septal defect, 3D print models are of enormous value in surgical decision and planning. Furthermore, 3D print models can also be used for rehearsal of the intended procedure before the actual surgery on the patient so that the outcome of the procedure is precisely predicted and the procedure can be optimally tailored for the patient's specific anatomy. 3D print models are invaluable resource for hands-on surgical training of congenital heart surgeons.

Definition of an intramolecular Eu-to-Eu energy transfer within a discrete [Eu2L] complex in solution.

PubMed

Nonat, Aline; Regueiro-Figueroa, Martín; Esteban-Gómez, David; de Blas, Andrés; Rodríguez-Blas, Teresa; Platas-Iglesias, Carlos; Charbonnière, Loïc J

2012-06-25

Ligand L, based on two do3a moieties linked by the methylene groups of 6,6'-dimethyl-2,2'-bipyridine, was synthesized and characterized. The addition of Ln salts to an aqueous solution of L (0.01 M Tris-HCl, pH 7.4) led to the successive formation of [LnL] and [Ln(2)L] complexes, as evidenced by UV/Vis and fluorescence titration experiments. Homodinuclear [Ln(2)L] complexes (Ln = Eu, Gd, Tb, Yb, and Lu) were prepared and characterized. The (1)H and (13)C NMR spectra of the Lu and Yb complexes in D(2)O solution (pD = 7.0) showed C(1) symmetry of these species in solution, pointing to two different chemical environments for the two lanthanide cations. The analysis of the chemical shifts of the Yb complex indicated that the two coordination sites present square antiprismatic (SAP) coordination environments around the metal ions. The spectroscopic properties of the [Tb(2)L] complex upon ligand excitation revealed conventional behavior with τ(H2O) = 2.05(1) ms and ϕ(H2O) = 51%, except for the calculation of the hydration number obtained from the luminescent lifetimes in H(2)O and D(2)O, which pointed to a non-integer value of 0.6 water molecules per Tb(III) ion. In contrast, the Eu complex revealed surprising features such as: 1) the presence of two and up to five components in the (5)D(0)→(7)F(0) and (5)D(0)→(7)F(1) emission bands, respectively; 2) marked differences between the normalized spectra obtained in H(2)O and D(2)O solutions; and 3) unconventional temporal evolution of the luminescence intensity at certain wavelengths, the intensity profile first displaying a rising step before the occurrence of the expected decay. Additional spectroscopic experiments performed on [Gd(2-x)Eu(x)L] complexes (x = 0.1 and 1.9) confirmed the presence of two distinct Eu sites with hydration numbers of 0 (site I) and 2 (site II), and showed that the unconventional temporal evolution of the emission intensity is the result of an unprecedented intramolecular Eu-to-Eu energy-transfer process. A mathematical model was developed to interpret the experimental data, leading to energy-transfer rates of 0.98 ms(-1) for the transfer from the site with q=0 to that with q=2 and vice versa. Hartree-Fock (HF) and density functional theory (DFT) calculations performed at the B3LYP level were used to investigate the conformation of the complex in solution, and to estimate the intermetallic distance, which provided Förster radii (R(0)) values of 8.1 Å for the energy transfer from site I to site II, and 6.8 Å for the reverse energy transfer. These results represent the first evidence of an intramolecular energy-transfer equilibrium between two identical lanthanide cations within a discrete molecular complex in solution. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Central Arctic Crustal Modeling Constrained by Potential Field data and recent ECS Seismic Data

NASA Astrophysics Data System (ADS)

Evangelatos, John; Oakey, Gordon; Saltus, Rick

2017-04-01

2-D gravity and magnetic models have been generated for several transects across the Alpha-Mendeleev ridge complex to study the regional variability of the crustal structure and identify large scale lateral changes. The geometry and density parameters for the models have been constrained using recently acquired seismic reflection and refraction data collected jointly by Canada and the United States as part of their collaborative Arctic ECS programs. A total of fifteen models have been generated perpendicular to the ridge complex, typically 50 to 150 km apart. A minimalist approach to modeling involved maintaining a simple, laterally continuous density structure for the crust while varying the model geometry to fit the observed gravity field. This approach is justified because low amplitude residual Bouguer anomalies suggest a relatively homogenous density structure within the ridge complex. These models have provided a new measure of the regional variability in crustal thickness. Typically, models with thinner crust correspond with deeper bathymetric depths of the ridge which is consistent with regional isostatic equilibrium. Complex "chaotic" magnetic anomalies are associated with the Alpha-Mendeleev ridge complex, which extends beneath the surrounding sedimentary basins. Pseudogravity inversion (magnetic potential) of the magnetic field provides a quantifiable areal extent of ˜1.3 x106 km2. Forward modeling confirms that the magnetic anomalies are not solely the result of magnetized bathymetric highs, but are caused to a great extent by mid- and lower crustal sources. The magnetization of the crust inferred from modeling is significantly higher than available lab measurements of onshore volcanic rocks. Although the 2-D models cannot uniquely identify whether the crustal protolith was continental or oceanic, there is a necessity for a significant content of high density and highly magnetic (ultramafic) material. Based on the crustal thickness estimates from our regional 2-D gravity models and the two possible protoliths, we determine volumetric estimates of the volcanic composition to ˜ 6 × 106 km3 for the mid- and upper-crust and between 10 × 106 and 14 × 106 km3 within the lower crust — for a total of at least ˜16 × 106 km3. This exceeds any estimates for the onshore circum-Arctic HALIP by more than an order of magnitude.

Elastic modulus and thermal stress in coating during heat cycling with different substrate shapes

NASA Astrophysics Data System (ADS)

Gaona, Daniel; Valarezo, Alfredo

2015-09-01

The elastic modulus of a deposit ( E d) can be obtained by monitoring the temperature (Δ T) and curvature (Δ k) of a one-side coated long plate, namely, a onedimensional (1D) deformation model. The aim of this research is to design an experimental setup that proves whether a 1D deformation model can be scaled for complex geometries. The setup includes a laser displacement sensor mounted on a robotic arm capable of scanning a specimen surface and measuring its deformation. The reproducibility of the results is verified by comparing the present results with Stony Brook University Laboratory's results. The Δ k-Δ T slope error is less than 8%, and the E d estimation error is close to 2%. These values reveal the repeatability of the experiments. Several samples fabricated with aluminum as the substrate and 100MXC nanowire (Fe and Cr alloy) as the deposit are analyzed and compared with those in finite element (FE) simulations. The linear elastic behavior of 1D (flat long plate) and 2D (squared plate) specimens during heating/cooling cycles is demonstrated by the high linearity of all Δ k-Δ T curves (over 97%). The E d values are approximately equal for 1D and 2D analyses, with a median of 96 GPa and standard deviation of 2 GPa. The correspondence between the experimental and simulated results for the 1D and 2D specimens reveals that deformation and thermal stress in coated specimens can be predicted regardless of specimen geometry through FE modeling and by using the experimental value of E d. An example of a turbine-bladeshaped substrate is presented to validate the approach.

Computational modeling of carbohydrate recognition in protein complex

NASA Astrophysics Data System (ADS)

Ishida, Toyokazu

2017-11-01

To understand the mechanistic principle of carbohydrate recognition in proteins, we propose a systematic computational modeling strategy to identify complex carbohydrate chain onto the reduced 2D free energy surface (2D-FES), determined by MD sampling combined with QM/MM energy corrections. In this article, we first report a detailed atomistic simulation study of the norovirus capsid proteins with carbohydrate antigens based on ab initio QM/MM combined with MD-FEP simulations. The present result clearly shows that the binding geometries of complex carbohydrate antigen are determined not by one single, rigid carbohydrate structure, but rather by the sum of averaged conformations mapped onto the minimum free energy region of QM/MM 2D-FES.

2D Spin Crossover Nanoparticles described by the Ising-like model solved in Local Mean-Field Approximation

NASA Astrophysics Data System (ADS)

Eddine Allal, Salah; Linares, Jorge; Boukheddaden, K.; Dahoo, Pierre Richard; de Zela, F.

2017-12-01

Some six-coordinate iron (II) coordination compounds exhibit thermal-, optical-, electrical-, magnetic- and pressure-induced switching between the diamagnetic low-spin (LS, S=0) and the paramagnetic high-spin (HS; S=2) states [1]. This may lead to potential application of these complexes in molecular devices such as temperature and pressure sensors [2]. An Ising-like model has been proposed to explain the occurrence of the thermal hysteresis behaviour [3,4] of this switchable solids. In this contribution, the local mean field approximation is applied to solve the Hamiltonian modelling interactions pertaining to 2D nanoparticles embedded in a magnetically-inactive matrix.

Pharmacodynamics of Amphotericin B Deoxycholate, Amphotericin B Lipid Complex, and Liposomal Amphotericin B against Aspergillus fumigatus

PubMed Central

Al-Nakeeb, Zaid; Petraitis, Vidmantas; Goodwin, Joanne; Petraitiene, Ruta; Walsh, Thomas J.

2015-01-01

Amphotericin B is a first-line agent for the treatment of invasive aspergillosis. However, relatively little is known about the pharmacodynamics of amphotericin B for invasive pulmonary aspergillosis. We studied the pharmacokinetics (PK) and pharmacodynamics (PD) of amphotericin B deoxycholate (DAMB), amphotericin B lipid complex (ABLC), and liposomal amphotericin B (LAMB) by using a neutropenic-rabbit model of invasive pulmonary aspergillosis. The study endpoints were lung weight, infarct score, and levels of circulating galactomannan and (1→3)-β-d-glucan. Mathematical models were used to describe PK-PD relationships. The experimental findings were bridged to humans by Monte Carlo simulation. Each amphotericin B formulation induced a dose-dependent decline in study endpoints. Near-maximal antifungal activity was evident with DAMB at 1 mg/kg/day and ABLC and LAMB at 5 mg/kg/day. The bridging study suggested that the “average” patient receiving LAMB at 3 mg/kg/day was predicted to have complete suppression of galactomannan and (1→3)-β-d-glucan levels, but 20 to 30% of the patients still had a galactomannan index of >1 and (1→3)-β-d-glucan levels of >60 pg/ml. All formulations of amphotericin B induce a dose-dependent reduction in markers of lung injury and circulating fungus-related biomarkers. A clinical dosage of liposomal amphotericin B of 3 mg/kg/day is predicted to cause complete suppression of galactomannan and (1→3)-β-d-glucan levels in the majority of patients. PMID:25712363

Normal-Gamma-Bernoulli Peak Detection for Analysis of Comprehensive Two-Dimensional Gas Chromatography Mass Spectrometry Data.

PubMed

Kim, Seongho; Jang, Hyejeong; Koo, Imhoi; Lee, Joohyoung; Zhang, Xiang

2017-01-01

Compared to other analytical platforms, comprehensive two-dimensional gas chromatography coupled with mass spectrometry (GC×GC-MS) has much increased separation power for analysis of complex samples and thus is increasingly used in metabolomics for biomarker discovery. However, accurate peak detection remains a bottleneck for wide applications of GC×GC-MS. Therefore, the normal-exponential-Bernoulli (NEB) model is generalized by gamma distribution and a new peak detection algorithm using the normal-gamma-Bernoulli (NGB) model is developed. Unlike the NEB model, the NGB model has no closed-form analytical solution, hampering its practical use in peak detection. To circumvent this difficulty, three numerical approaches, which are fast Fourier transform (FFT), the first-order and the second-order delta methods (D1 and D2), are introduced. The applications to simulated data and two real GC×GC-MS data sets show that the NGB-D1 method performs the best in terms of both computational expense and peak detection performance.

Genetic approach to reconstruct complex regional geological setting of the Baltic basin in 3D geological model

NASA Astrophysics Data System (ADS)

Popovs, K.; Saks, T.; Ukass, J.; Jatnieks, J.

2012-04-01

Interpretation of geological structures in 3D geological models is a relatively new research topic that is already standardized in many geological branches. Due to its wide practical application, these models are indispensable and become one of the dominant interpretation methods in reducing geological uncertainties in many geology fields. Traditionally, geological concepts complement quantitative as much as qualitative data to obtain a model deemed acceptable, however, available data very often is insufficient and modeling methods primarily focus on spatial data but geological history usually is mostly neglected for the modeling of large sedimentary basins. A need to better integrate the long and often complex geological history and geological knowledge into modeling procedure is very acute to gain geological insight and improve the quality of geological models. During this research, 3D geological model of the Baltic basin (BB) was created. Because of its complex regional geological setting - wide range of the data sources with multiple scales, resolution and density as well as its various source formats, the study area provides a challenge for the 3D geological modeling. In order to create 3D regional geometrical model for the study area algorithmic genetic approach for model geometry reconstruction was applied. The genetic approach is based on the assumption that post-depositional deformation produce no significant change in sedimentary strata volume, assuming that the strata thickness and its length in a cross sectional plane remains unchanged except as a result of erosion. Assuming that the tectonic deformation occurred in sequential cycles and subsequent tectonic stage strata is separated by regional unconformity as is the case of the BB, there is an opportunity for algorithmic approach in reconstructing these conditions by sequentially reconstructing the layer original thickness. Layer thicknesses were sliced along fault lines, where applicable layer thickness was adjusted by taking into account amount of erosion by the presence of the regional unconformities. Borehole data and structural maps of some surfaces were used in creating geological model of the BB. Used approach allowed creating geologically sound geometric model. At first borehole logs were used to reconstruct initial thicknesses of different strata in every tectonic stage, where topography of each strata was obtained sequentially summing thickness to the initial reference surface from structural maps. Thereby each layer reflects the topography and amount of slip along the fault of the overlying layer. Overlying tectonic cycle sequence is implemented into the model structure by using unconformity surface as an initial reference surface. Applied techniques made possible reliably reconstructing and predicting in areas of sparse data layer surface geometry, its thickness distribution and evaluating displacements along the fault planes. Overall results indicate that the used approach has a good potential in development of regional geological models for the sedimentary basins and is valid for spatial interpretation of geological structures, subordinating this process to geological evolution prerequisites. This study is supported by the European Social Fund project No. 2009/0212/1DP/1.1.1.2.0/09/APIA/VIAA/060.

Technetium glucose complexes as potential cancer imaging agents.

PubMed

Dapueto, Rosina; Aguiar, Rodrigo B; Moreno, María; Machado, Camila M L; Marques, Fabio L N; Gambini, Juan P; Chammas, Roger; Cabral, Pablo; Porcal, Williams

2015-10-01

GLUT's (facilitative glucose transporters) over-expression in tumor cells has allowed the detection of several cancer types, using a glucose analogue ((18)F-FDG) with PET images, worldwide. New glucose analogs radiolabeled with (99m)Tc could be a less-expensive and more accessible alternative for diagnosis using SPECT imaging. d-Glucose ((99m)Tc-IDAG) and 2-d-deoxyglucose ((99m)Tc-AADG) organometallic complexes were proposed and studied as potential (18)F-FDG surrogates. The glucose complexes were prepared and evaluated as potential cancer imaging agents, in a melanoma tumor model. Iminodiacetic acid (IDA) and aminoacetate (AA) moieties were chosen as chelating system for radiolabeling with (99m)Tc. Tumor uptake of the formed complexes was evaluated in B16 murine cell line in vitro and in vivo in melanoma bearing C57BL/6 mice. In vitro and in vivo studies were conducted with (18)F-FDG in order to compare the uptake of (99m)Tc-glucose complexes in the tumor model. IDAG and AADG compounds were synthesized and radiolabeled with (99m)TcO4(-) to obtain the (99m)Tc-IDAG and (99m)Tc-AADG complexes in high yield and stability. In vitro cell studies showed maximum uptake at 60 min for complexes, (99m)Tc-IDAG and (99m)Tc-AADG, with 6% and 2%, respectively. Biodistribution studies showed high tumor uptake one hour post-injection, reaching tumor-to-muscle ratios of 12.1 ± 3.73 and 2.88 ± 1.40 for (99m)Tc-IDAG and (99m)Tc-AADG, respectively. SPECT and micro-SPECT-CT images acquired after the injection of (99m)Tc-IDAG showed accumulation in tumor sites, suggesting that this glucose complex would be a promising candidate for cancer imaging. Copyright © 2015 Elsevier Ltd. All rights reserved.

Using basic metrics to analyze high-resolution temperature data in the subsurface

NASA Astrophysics Data System (ADS)

Shanafield, Margaret; McCallum, James L.; Cook, Peter G.; Noorduijn, Saskia

2017-08-01

Time-series temperature data can be summarized to provide valuable information on spatial variation in subsurface flow, using simple metrics. Such computationally light analysis is often discounted in favor of more complex models. However, this study demonstrates the merits of summarizing high-resolution temperature data, obtained from a fiber optic cable installation at several depths within a water delivery channel, into daily amplitudes and mean temperatures. These results are compared to fluid flux estimates from a one-dimensional (1D) advection-conduction model and to the results of a previous study that used a full three-dimensional (3D) model. At a depth of 0.1 m below the channel, plots of amplitude suggested areas of advective water movement (as confirmed by the 1D and 3D models). Due to lack of diurnal signal at depths below 0.1 m, mean temperature was better able to identify probable areas of water movement at depths of 0.25-0.5 m below the channel. The high density of measurements provided a 3D picture of temperature change over time within the study reach, and would be suitable for long-term monitoring in man-made environments such as constructed wetlands, recharge basins, and water-delivery channels, where a firm understanding of spatial and temporal variation in infiltration is imperative for optimal functioning.

Construction, Structural Diversity and Properties of Five Coordination Polymers Based on 5-Nitroisophthalate and Bis(imidazole) Linkers

NASA Astrophysics Data System (ADS)

Arıcı, Mürsel

2018-06-01

Five coordination polymers, namely, [Cd(μ3-5-nip)(μ-obix)]n (1), [Co(μ3-5-nip)(μ-obix)]n (2), [Zn(μ-5-nip)(μ-obix)]n (3 and 4) and [Cd(μ-5-nip)(μ-bisobix)]n (5) (5-nip: 5-nitroisophthalate, obix: 1,2-bis(imidazol-1ylmethyl)benzene, bisobix: 1,2-bis(2-isopropylimidazol-1ylmethyl)benzene) were hydrothermally synthesized and characterized by IR spectroscopy, elemental analysis, single crystal and powder X-ray diffraction and thermal analysis (TG/DTA). X-ray results showed that the complexes displayed structural diversity depending on metal ions and conformations of bis(imidazole) linkers. Complexes 1 and 2 were 1D structures and obix ligand displayed cis-conformation. Complexes 3 and 4 exhibited 2D and 3D structures with same components depending on obix conformation. In complex 5, 3D+3D→3D interpenetrated structure was obtained with dia topology when bisobix having sterically hindered groups on imidazole rings was used. Moreover, thermal, photoluminescence and optical properties of the complexes were also investigated.

New coordination polymers from 1D chain, 2D layer to 3D framework constructed from 1,2-phenylenediacetic acid and 1,3-bis(4-pyridyl)propane flexible ligands

NASA Astrophysics Data System (ADS)

Xin, Ling-Yun; Liu, Guang-Zhen; Wang, Li-Ya

2011-06-01

The hydrothermal reactions of Cd, Zn, or Cu(II) acetate salts with H 2PHDA and BPP flexible ligands afford three new coordination polymers, including [Cd(PHDA)(BPP)(H 2O)] n(1), [Zn(PHDA)(BPP)] n(2), and [Cu 2(PHDA) 2(BPP)] n(3) (H 2PHDA=1,2-phenylenediacetic acid, BPP=1,3-bis(4-pyridyl)propane). The single-crystal X-ray diffractions reveal that all three complexes feature various metal carboxylate subunits extended further by the BPP ligands to form a diverse range of structures, displaying a remarked structural sensitivity to metal(II) cation. Complex 1 containing PHDA-bridged binuclear cadmium generates 1D double-stranded chain, complex 2 results in 2D→2D interpenetrated (4,4) grids, and complex 3 displays a 3D self-penetrated framework with 4 86 68 rob topology. In addition, fluorescent analyses show that both 1 and 2 exhibit intense blue-violet photoluminescence in the solid state.

Transcontinental Phylogeography of the Daphnia pulex Species Complex

PubMed Central

Costanzo, Katie S.; Taylor, Derek J.

2012-01-01

Daphnia pulex is quickly becoming an attractive model species in the field of ecological genomics due to the recent release of its complete genome sequence, a wide variety of new genomic resources, and a rich history of ecological data. Sequences of the mitochondrial NADH dehydrogenase subunit 5 and cytochrome c oxidase subunit 1 genes were used to assess the global phylogeography of this species, and to further elucidate its phylogenetic relationship to other members of the Daphnia pulex species complex. Using both newly acquired and previously published data, we analyzed 398 individuals from collections spanning five continents. Eleven strongly supported lineages were found within the D. pulex complex, and one lineage in particular, panarctic D. pulex, has very little phylogeographical structure and a near worldwide distribution. Mismatch distribution, haplotype network, and population genetic analyses are compatible with a North American origin for this lineage and subsequent spatial expansion in the Late Pleistocene. In addition, our analyses suggest that dispersal between North and South America of this and other species in the D. pulex complex has occurred multiple times, and is predominantly from north to south. Our results provide additional support for the evolutionary relationships of the eleven main mitochondrial lineages of the D. pulex complex. We found that the well-studied panarctic D. pulex is present on every continent except Australia and Antarctica. Despite being geographically very widespread, there is a lack of strong regionalism in the mitochondrial genomes of panarctic D. pulex – a pattern that differs from that of most studied cladocerans. Moreover, our analyses suggest recent expansion of the panarctic D. pulex lineage, with some continents sharing haplotypes. The hypothesis that hybrid asexuality has contributed to the recent and unusual geographic success of the panarctic D. pulex lineage warrants further study. PMID:23056371

Transcontinental phylogeography of the Daphnia pulex species complex.

PubMed

Crease, Teresa J; Omilian, Angela R; Costanzo, Katie S; Taylor, Derek J

2012-01-01

Daphnia pulex is quickly becoming an attractive model species in the field of ecological genomics due to the recent release of its complete genome sequence, a wide variety of new genomic resources, and a rich history of ecological data. Sequences of the mitochondrial NADH dehydrogenase subunit 5 and cytochrome c oxidase subunit 1 genes were used to assess the global phylogeography of this species, and to further elucidate its phylogenetic relationship to other members of the Daphnia pulex species complex. Using both newly acquired and previously published data, we analyzed 398 individuals from collections spanning five continents. Eleven strongly supported lineages were found within the D. pulex complex, and one lineage in particular, panarctic D. pulex, has very little phylogeographical structure and a near worldwide distribution. Mismatch distribution, haplotype network, and population genetic analyses are compatible with a North American origin for this lineage and subsequent spatial expansion in the Late Pleistocene. In addition, our analyses suggest that dispersal between North and South America of this and other species in the D. pulex complex has occurred multiple times, and is predominantly from north to south. Our results provide additional support for the evolutionary relationships of the eleven main mitochondrial lineages of the D. pulex complex. We found that the well-studied panarctic D. pulex is present on every continent except Australia and Antarctica. Despite being geographically very widespread, there is a lack of strong regionalism in the mitochondrial genomes of panarctic D. pulex--a pattern that differs from that of most studied cladocerans. Moreover, our analyses suggest recent expansion of the panarctic D. pulex lineage, with some continents sharing haplotypes. The hypothesis that hybrid asexuality has contributed to the recent and unusual geographic success of the panarctic D. pulex lineage warrants further study.

3D-Reconstructions and Virtual 4D-Visualization to Study Metamorphic Brain Development in the Sphinx Moth Manduca Sexta

PubMed Central

Huetteroth, Wolf; el Jundi, Basil; el Jundi, Sirri; Schachtner, Joachim

2009-01-01

During metamorphosis, the transition from the larva to the adult, the insect brain undergoes considerable remodeling: new neurons are integrated while larval neurons are remodeled or eliminated. One well acknowledged model to study metamorphic brain development is the sphinx moth Manduca sexta. To further understand mechanisms involved in the metamorphic transition of the brain we generated a 3D standard brain based on selected brain areas of adult females and 3D reconstructed the same areas during defined stages of pupal development. Selected brain areas include for example mushroom bodies, central complex, antennal- and optic lobes. With this approach we eventually want to quantify developmental changes in neuropilar architecture, but also quantify changes in the neuronal complement and monitor the development of selected neuronal populations. Furthermore, we used a modeling software (Cinema 4D) to create a virtual 4D brain, morphing through its developmental stages. Thus the didactical advantages of 3D visualization are expanded to better comprehend complex processes of neuropil formation and remodeling during development. To obtain datasets of the M. sexta brain areas, we stained whole brains with an antiserum against the synaptic vesicle protein synapsin. Such labeled brains were then scanned with a confocal laser scanning microscope and selected neuropils were reconstructed with the 3D software AMIRA 4.1. PMID:20339481

3D-Reconstructions and Virtual 4D-Visualization to Study Metamorphic Brain Development in the Sphinx Moth Manduca Sexta.

PubMed

Huetteroth, Wolf; El Jundi, Basil; El Jundi, Sirri; Schachtner, Joachim

2010-01-01

DURING METAMORPHOSIS, THE TRANSITION FROM THE LARVA TO THE ADULT, THE INSECT BRAIN UNDERGOES CONSIDERABLE REMODELING: new neurons are integrated while larval neurons are remodeled or eliminated. One well acknowledged model to study metamorphic brain development is the sphinx moth Manduca sexta. To further understand mechanisms involved in the metamorphic transition of the brain we generated a 3D standard brain based on selected brain areas of adult females and 3D reconstructed the same areas during defined stages of pupal development. Selected brain areas include for example mushroom bodies, central complex, antennal- and optic lobes. With this approach we eventually want to quantify developmental changes in neuropilar architecture, but also quantify changes in the neuronal complement and monitor the development of selected neuronal populations. Furthermore, we used a modeling software (Cinema 4D) to create a virtual 4D brain, morphing through its developmental stages. Thus the didactical advantages of 3D visualization are expanded to better comprehend complex processes of neuropil formation and remodeling during development. To obtain datasets of the M. sexta brain areas, we stained whole brains with an antiserum against the synaptic vesicle protein synapsin. Such labeled brains were then scanned with a confocal laser scanning microscope and selected neuropils were reconstructed with the 3D software AMIRA 4.1.

Modeling the protonation states of β-secretase binding pocket by molecular dynamics simulations and docking studies.

PubMed

Sabbah, Dima A; Zhong, Haizhen A

2016-07-01

β-secretase (BACE1) is an aspartyl protease that processes the β-amyloid peptide in the human brain in patients with Alzheimer's disease. There are two catalytic aspartates (ASP32 and ASP228) in the active domain of BACE1. Although it is believed that the net charge of the Asp dyad is -1, the exact protonation state still remains a matter of debate. We carried out molecular dynamic (MD) simulations for the four protonation states of BACE1 proteins. We applied Glide docking studies to 21 BACE1 inhibitors against the MD extracted conformations. The dynamic results infer that the protein/ligand complex remains stable during the entire simulation course for HD32D228 model. The results show that the hydrogen bonds between the inhibitor and the Asp dyad are maintained in the 10,000th ps snapshot of HD32D228 model. Our results also reveal the significant loop residues in maintaining the active binding conformation in the HD32D228 model. Molecular docking results show that the HD32D228 model provided the best enrichment factor score, suggesting that this model was able to recognize the most active compounds. Our observations provide an evidence for the preference of the anionic state (HD32D228) in BACE1 binding site and are in accord with reported computational data. The protonation state study would provide significant information to assign the correct protonation state for structure-based drug design and docking studies targeting the BACE1 proteins as a tactic to develop potential AD inhibitors. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Adaptive Model-Predictive Motion Planning for Navigation in Complex Environments

DTIC Science & Technology

2009-08-01

AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Carnegie Mellon University,The...Robotics Institute,Pittsburgh,PA,15213 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR...6 1.5 Assumptions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.6 Organization

Simulation of Grouting Process in Rock Masses Under a Dam Foundation Characterized by a 3D Fracture Network

NASA Astrophysics Data System (ADS)

Deng, Shaohui; Wang, Xiaoling; Yu, Jia; Zhang, Yichi; Liu, Zhen; Zhu, Yushan

2018-06-01

Grouting plays a crucial role in dam safety. Due to the concealment of grouting activities, complexity of fracture distribution in rock masses and rheological properties of cement grout, it is difficult to analyze the effects of grouting. In this paper, a computational fluid dynamics (CFD) simulation approach of dam foundation grouting based on a 3D fracture network model is proposed. In this approach, the 3D fracture network model, which is based on an improved bootstrap sampling method and established by VisualGeo software, can provide a reliable and accurate geometric model for CFD simulation of dam foundation grouting. Based on the model, a CFD simulation is performed, in which the Papanastasiou regularized model is used to express the grout rheological properties, and the volume of fluid technique is utilized to capture the grout fronts. Two sets of tests are performed to verify the effectiveness of the Papanastasiou regularized model. When applying the CFD simulation approach for dam foundation grouting, three technical issues can be solved: (1) collapsing potential of the fracture samples, (2) inconsistencies in the geometric model in actual fractures under complex geological conditions, and (3) inappropriate method of characterizing the rheological properties of cement grout. The applicability of the proposed approach is demonstrated by an illustrative case study—a hydropower station dam foundation in southwestern China.

Pumping Optimization Model for Pump and Treat Systems - 15091

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

Baker, S.; Ivarson, Kristine A.; Karanovic, M.

2015-01-15

Pump and Treat systems are being utilized to remediate contaminated groundwater in the Hanford 100 Areas adjacent to the Columbia River in Eastern Washington. Design of the systems was supported by a three-dimensional (3D) fate and transport model. This model provided sophisticated simulation capabilities but requires many hours to calculate results for each simulation considered. Many simulations are required to optimize system performance, so a two-dimensional (2D) model was created to reduce run time. The 2D model was developed as a equivalent-property version of the 3D model that derives boundary conditions and aquifer properties from the 3D model. It producesmore » predictions that are very close to the 3D model predictions, allowing it to be used for comparative remedy analyses. Any potential system modifications identified by using the 2D version are verified for use by running the 3D model to confirm performance. The 2D model was incorporated into a comprehensive analysis system (the Pumping Optimization Model, POM) to simplify analysis of multiple simulations. It allows rapid turnaround by utilizing a graphical user interface that: 1 allows operators to create hypothetical scenarios for system operation, 2 feeds the input to the 2D fate and transport model, and 3 displays the scenario results to evaluate performance improvement. All of the above is accomplished within the user interface. Complex analyses can be completed within a few hours and multiple simulations can be compared side-by-side. The POM utilizes standard office computing equipment and established groundwater modeling software.« less

Sage Simulation Model for Technology Demonstration Convertor by a Step-by-Step Approach

NASA Technical Reports Server (NTRS)

Demko, Rikako; Penswick, L. Barry

2006-01-01

The development of a Stirling model using the 1-D Saga design code was completed using a step-by-step approach. This is a method of gradually increasing the complexity of the Saga model while observing the energy balance and energy losses at each step of the development. This step-by-step model development and energy-flow analysis can clarify where the losses occur, their impact, and suggest possible opportunities for design improvement.

Numerical simulation of radiation fog in complex terrain

NASA Astrophysics Data System (ADS)

Zhang, X.; Musson-Genon, L.; Carissimo, B.; Dupont, E.

2009-09-01

The interest for micro-scale modeling of the atmosphere is growing for environmental applications related, for example, to energy production, transport and urban development. The turbulence in the stable layers where pollutant dispersion is low and can lead to strong pollution events. This could be further complicated by the presence of clouds or fog and is specifically difficult in urban or industrial area due to the presence of buildings. In this context, radiation fog formation and dissipation over complex terrain were therefore investigated with a state-of-the-art model. This study is divided into two phases. The first phase is a pilot stage, which consist of employing a database from the ParisFog campaign which took place in the south of Paris during winter 2006-07 to assess the ability of the cloud model to reproduce the detailed structure of radiation fog. The second phase use the validated model for the study of influence of complex terrain on fog evolution. Special attention is given to the detailed and complete simulations and validation technique used is to compare the simulated results using the 3D cloud model of computational fluid dynamical software Code_Saturne with one of the best collected in situ data during the ParisFog campaign. Several dynamical, microphysical parameterizations and simulation conditions have been described. The resulting 3D cloud model runs at a horizontal resolution of 30 m and a vertical resolution comparable to the 1D model. First results look very promising and are able to reproduce the spatial distribution of fog. The analysis of the behavior of the different parameterized physical processes suggests that the subtle balance between the various processes is achieved.

Long-term patency of complex bilobular, bisaccular, and broad-neck aneurysms in the rabbit microsurgical venous pouch bifurcation model.

PubMed

Marbacher, Serge; Tastan, Ilhan; Neuschmelting, Volker; Erhardt, Salome; Coluccia, Daniel; Sherif, Camillo; Remonda, Luca; Fandino, Javier

2012-07-01

In experimental aneurysm models, long-term patency without spontaneous thrombosis is the most important precondition for analyses of embolization devices. We recently reported the feasibility of creating complex venous pouch bifurcation aneurysms in the rabbit with low morbidity, low mortality, and high short-term aneurysm patency. In order to further evaluate our model, we examined the long-term patency rate. Various sizes of complex bilobular, bisaccular, and broad-neck venous pouch aneurysms were surgically formed at an artificially created bifurcation of both common carotid arteries in 17 rabbits. Early aggressive anticoagulation was continued for 1 month. The rabbits were followed up using contrast-enhanced three-dimensional 1.5-T magnetic resonance angiography (CE-3D-MRA) at 1 month and up to 1 year after creation of the bifurcation. At 1-month follow-up, all but one of the created aneurysms and all parent vessels proved to be patent. Three animals (18%) were lost during follow-up for reasons unrelated to aneurysm surgery. At 1-year follow-up, one animal showed partial and one complete spontaneous aneurysm thrombosis (aneurysm patency rate: 86%). Six out of 42 parent vessels were occluded at that time (vessel patency rate: 86%). Complex bilobular, bisaccular, and broad-neck microsurgical aneurysm formation in the rabbit bifurcation model demonstrates a high long-term patency rate but is complicated by high rates of unrelated procedural mortality and morbidity. There is no need for prolonged (>4 weeks) anticoagulation to achieve good long-term patency in complex venous pouch bifurcation aneurysms.

Native Electrospray Ionization Mass Spectrometry Reveals Multiple Facets of Aptamer-Ligand Interactions: From Mechanism to Binding Constants.

PubMed

Gülbakan, Basri; Barylyuk, Konstantin; Schneider, Petra; Pillong, Max; Schneider, Gisbert; Zenobi, Renato

2018-06-20

Aptamers are oligonucleotide receptors obtained through an iterative selection process from random-sequence libraries. Though many aptamers for a broad range of targets with high affinity and selectivity have been generated, a lack of high-resolution structural data and the limitations of currently available biophysical tools greatly impede understanding of the mechanisms of aptamer-ligand interactions. Here we demonstrate that an approach based on native electrospray ionization mass spectrometry (ESI-MS) can be successfully applied to characterize aptamer-ligand complexes in all details. We studied an adenosine-binding aptamer (ABA), a l-argininamide-binding aptamer (LABA), and a cocaine-binding aptamer (CBA) and their noncovalent interactions with ligands by native ESI-MS and complemented these measurements by ion mobility spectrometry (IMS), isothermal titration calorimetry (ITC), and circular dichroism (CD) spectroscopy. The ligand selectivity of the aptamers and the respective complex stoichiometry could be determined by the native ESI-MS approach. The ESI-MS data can also help refining the binding model for aptamer-ligand complexes and deliver accurate aptamer-ligand binding affinities for specific and nonspecific binding events. For specific ligands, we found K d1 = 69.7 μM and K d2 = 5.3 μM for ABA (two binding sites); K d1 = 22.04 μM for LABA; and K d1 = 8.5 μM for CBA.

Inner-sphere complexation of cations at the rutile-water interface: A concise surface structural interpretation with the CD and MUSIC model

NASA Astrophysics Data System (ADS)

Ridley, Moira K.; Hiemstra, Tjisse; van Riemsdijk, Willem H.; Machesky, Michael L.

2009-04-01

Acid-base reactivity and ion-interaction between mineral surfaces and aqueous solutions is most frequently investigated at the macroscopic scale as a function of pH. Experimental data are then rationalized by a variety of surface complexation models. These models are thermodynamically based which in principle does not require a molecular picture. The models are typically calibrated to relatively simple solid-electrolyte solution pairs and may provide poor descriptions of complex multi-component mineral-aqueous solutions, including those found in natural environments. Surface complexation models may be improved by incorporating molecular-scale surface structural information to constrain the modeling efforts. Here, we apply a concise, molecularly-constrained surface complexation model to a diverse suite of surface titration data for rutile and thereby begin to address the complexity of multi-component systems. Primary surface charging curves in NaCl, KCl, and RbCl electrolyte media were fit simultaneously using a charge distribution (CD) and multisite complexation (MUSIC) model [Hiemstra T. and Van Riemsdijk W. H. (1996) A surface structural approach to ion adsorption: the charge distribution (CD) model. J. Colloid Interf. Sci. 179, 488-508], coupled with a Basic Stern layer description of the electric double layer. In addition, data for the specific interaction of Ca 2+ and Sr 2+ with rutile, in NaCl and RbCl media, were modeled. In recent developments, spectroscopy, quantum calculations, and molecular simulations have shown that electrolyte and divalent cations are principally adsorbed in various inner-sphere configurations on the rutile 1 1 0 surface [Zhang Z., Fenter P., Cheng L., Sturchio N. C., Bedzyk M. J., Předota M., Bandura A., Kubicki J., Lvov S. N., Cummings P. T., Chialvo A. A., Ridley M. K., Bénézeth P., Anovitz L., Palmer D. A., Machesky M. L. and Wesolowski D. J. (2004) Ion adsorption at the rutile-water interface: linking molecular and macroscopic properties. Langmuir20, 4954-4969]. Our CD modeling results are consistent with these adsorbed configurations provided adsorbed cation charge is allowed to be distributed between the surface (0-plane) and Stern plane (1-plane). Additionally, a complete description of our titration data required inclusion of outer-sphere binding, principally for Cl - which was common to all solutions, but also for Rb + and K +. These outer-sphere species were treated as point charges positioned at the Stern layer, and hence determined the Stern layer capacitance value. The modeling results demonstrate that a multi-component suite of experimental data can be successfully rationalized within a CD and MUSIC model using a Stern-based description of the EDL. Furthermore, the fitted CD values of the various inner-sphere complexes of the mono- and divalent ions can be linked to the microscopic structure of the surface complexes and other data found by spectroscopy as well as molecular dynamics (MD). For the Na + ion, the fitted CD value points to the presence of bidenate inner-sphere complexation as suggested by a recent MD study. Moreover, its MD dominance quantitatively agrees with the CD model prediction. For Rb +, the presence of a tetradentate complex, as found by spectroscopy, agreed well with the fitted CD and its predicted presence was quantitatively in very good agreement with the amount found by spectroscopy.

Three-dimensional structure of cofilin bound to monomeric actin derived by structural mass spectrometry data

PubMed Central

Kamal, J. K. Amisha; Benchaar, Sabrina A.; Takamoto, Keiji; Reisler, Emil; Chance, Mark R.

2007-01-01

The cytoskeletal protein, actin, has its structure and function regulated by cofilin. In the absence of an atomic resolution structure for the actin/cofilin complex, the mechanism of cofilin regulation is poorly understood. Theoretical studies based on the similarities of cofilin and gelsolin segment 1 proposed the cleft between subdomains 1 and 3 in actin as the cofilin binding site. We used radiolytic protein footprinting with mass spectrometry and molecular modeling to provide an atomic model of how cofilin binds to monomeric actin. Footprinting data suggest that cofilin binds to the cleft between subdomains 1 and 2 in actin and that cofilin induces further closure of the actin nucleotide cleft. Site-specific fluorescence data confirm these results. The model identifies key ionic and hydrophobic interactions at the binding interface, including hydrogen-bonding between His-87 of actin to Ser-89 of cofilin that may control the charge dependence of cofilin binding. This model and its implications fill an especially important niche in the actin field, owing to the fact that ongoing crystallization efforts of the actin/cofilin complex have so far failed. This 3D binary complex structure is derived from a combination of solution footprinting data and computational approaches and outlines a general method for determining the structure of such complexes. PMID:17470807

3D groundwater modeling of the Upper Mega Aquifer System (Arabian Peninsula) using OpenGeoSys

NASA Astrophysics Data System (ADS)

Schulz, Stephan; Rausch, Randolf; Siebert, Christian; Michelsen, Nils; Kolditz, Olaf; Al-Saud, Mohammed I.; Schüth, Christoph

2013-04-01

Groundwater is the only relevant freshwater resource for most countries on the Arabian Peninsula. Due to almost no recharge in most of the areas a sustainable management of this resource is not possible. Nevertheless, a smart and intelligent mining of groundwater can extend its lifetime. For this purpose groundwater models can be applied as powerful management tools. In this work a 3D groundwater model for the most relevant aquifer complex on the Arabian Peninsula, the Upper Mega Aquifer System, will be setup by using OpenGeoSys. The aquifer system has an extent of approximately 1.7 Mio. km2 and comprises 12 hydrogeological units from the Lower Cretaceous to the Neogene. The model serves the purpose to understand the system better and makes it possible to calculate scenarios of different abstraction rates and places. It could also help to quantify complex water balance components like the discharge into the Arabian Gulf. In order to setup the model further research as the estimation of important sink and source terms like groundwater recharge and Sabkha evaporation will be implemented.

Structures of Mid-Polish Trough in the light of regional magnetotelluric survey

NASA Astrophysics Data System (ADS)

Stefaniuk, M.; Pokorski, J.; Wojdyla, M.; Klitynski, W.

2009-04-01

Introduction The magnetotelluric survey at three long regional profiles crossing the Mid-Polish Trough in north-western part of Poland was made during 2005-2008 period. Two of the profiles pass across the Pomeranian section of the Trough and the third one cuts its Kujawy section. The task of the survey was to recognize the geological structure of the contact zone of Precambrian East European Craton and Paleozoic Platform of Western Europe. The profiles crossed major geological structures of central and north-western Poland, including the Variscan Externides and Varscian Foredeep, the Transeuropean Suture Zone and the marginal zone of the East European Craton. The main objectives of the project included evaluation of resistivity distribution and identification of structures of sub-Zechstein sedimentary and metamorphic complexes.The screening of seismic energy by high reflective Zechstein evaporates is the main problem in identifying the sub-Zechstein complexes in the Polish Lowlands area. Since evaporates do not screen the electromagnetic waves, the magnetotelluric method can be advantageously applied. The sub-Zechstein complexes and structures are commonly considered as hydrocarbon prospective. A lot of gas deposits have been discovered in Rotliegend sediments in central and Western Europe. A number offshore and onshore oil fields were found in Cambrian sandstones in the Baltic Sea area. Techniques and methodology of surveys Magnetotelluric measurements were taken with the use of MT-1 system of Electromagnetic Instruments Incorporation (EMI), Richmond, California, USA and System 2000.net based on V8 receiver of Phoenix Geophysics Ltd., Ottawa, Canada. An average spacing of sounding sites was about 4 km. The components of natural electromagnetic field were recorded over a broad range of frequencies, ranging from 0.0003 Hz to 575 Hz (MT-1) and 0,0003 HZ to 10 000,0 HZ (System 2000.net). This frequency band allowed information on the geology from a depth range of a few dozen meters to approximately 100 km to be obtained. A remote reference site was located at a distance of over 100 km of the study area. Data processing and interpretation Processing of the recorded data included the estimation of the components of impedance tensor (Zxx, Zxy, Zyx and Zyy ), with the use of robust procedures. The components of the impedance tensor enabled calculation of field curves for two orientations of the measurement system and additional parameters of the medium like skew, strike, pole diagrams etc. Recording of the vertical component of electromagnetic field (Hz) enabled the tipper parameter, T, to be calculated. Geophysical interpretation of MT sounding data along profiles was based on 1D inversion and 2D inversion. The upper part of the geological section is built of relatively flat layers; hence a 1D interpretation model could be effectively applied. Starting models for 1D inversion were constructed based on results of electromagnetic well-logging data. Some well-documented seismic horizons were taken as constraints in 1D inversion. The first step in 2D MT inversion was the calculation of inverse model with stabilized parameters of the upper part of geological section over the top of Zechstein complex. The starting model was obtained with the use of available geological cross-sections interpreted based on borehole and reflection seismic data. Results of inversion for the lower part of the section with constrained its upper part made some misfits between calculated and post-processed magnetotelluric curves. The second step in geophysical interpretation was 2D inversion with no constraints, which was finished when the misfit was small. Results of the first step of 2D inversion were applied as a starting model. Depending on inversion parameters, final resistivity distribution model along profiles was obtained. Geological interpretation was made based on resistivity cross-sections and borehole and reflection seismic data. Of great interest is varied resistivity of the formation resting below the Zechstein evaporate complex. As a result of data interpretation geophysical and geological sections were constructed. Conclusions As a result of magnetotelluric data interpretation, a tectonic model along measurement profiles with fault zones was constructed and lithology differentiation of sub-Zechstein complex was determined. Deep magnetotelluric cross-sections with interpretation of sub-Zechstein structures across the Polish Lowlands help to understand geodynamic processes in the area. Acknowledgments. This paper was based on results of investigations carried out by the PBG Geophysical Exploration Company Ltd. financed by Ministry of Environment trough National Fund for Environment Protection and Water Resources. The authors used also results of statutory research of Department of General Geology, Environment Protection and Geotourism, UST AGH, financed by the Minister of Science and Higher Education (project no 11.11.140.447). Interpretation was carried out using software by EMI, and Geosystem WingLinkTM.

Hydrogen bonding in water clusters and their ionized counterparts.

PubMed

Neela, Y Indra; Mahadevi, A Subha; Sastry, G Narahari

2010-12-30

Ab initio and DFT computations were carried out on four distinct hydrogen-bonded arrangements of water clusters (H(2)O)(n), n = 2-20, represented as W1D, W2D, W2DH, and W3D. The variation in the strength of hydrogen bond as a function of the chain length is studied. In all the four cases, there is a substantial cooperative interaction, albeit in different degrees. The effect of basis set superposition error (BSSE) on the complexation energy of water clusters has been analyzed. Atoms in molecules (AIM) analysis performed to evaluate the nature of the hydrogen bonding shows a high correlation between hydrogen bond strength and the trends in complexation energy. Solvated water clusters exhibit lower complexation energies compared to corresponding gas-phase geometries on PCM (polarized continuum model) optimization. The feasibility of stripping an electron or addition of an electron increases dramatically as the cluster size increases. Although W3D caged structures are stable for neutral clusters, the helical W2DH arrangement appeared to be an optimal choice for its ionized counterparts.

Magnetic Properties of Mononuclear Co(II) Complexes with Carborane Ligands.

PubMed

Alcoba, Diego R; Oña, Ofelia B; Massaccesi, Gustavo E; Torre, Alicia; Lain, Luis; Melo, Juan I; Peralta, Juan E; Oliva-Enrich, Josep M

2018-06-12

We analyze the magnetic properties of three mononuclear Co(II) coordination complexes using quantum chemical complete active space self-consistent field and N-electron valence perturbation theory approaches. The complexes are characterized by a distorted tetrahedral geometry in which the central ion is doubly chelated by the icosahedral ligands derived from 1,2-(HS) 2 -1,2-C 2 B 10 H 10 (complex I), from 1,2-(HS) 2 -1,2-C 2 B 10 H 10 and 9,12-(HS) 2 -1,2-C 2 B 10 H 10 (complex II), and from 9,12-(HS) 2 -1,2-C 2 B 10 H 10 (complex III), which are two positional isomers of dithiolated 1,2-dicarba- closo-dodecaborane (complex I). Complex I was realized experimentally recently (Tu, D.; Shao, D.; Yan, H.; Lu, C. Chem. Commun. 2016, 52, 14326) and served to validate the computational protocol employed in this work, while the remaining two proposed complexes can be considered positional isomers of I. Our calculations show that these complexes present different axial and rhombic zero-field splitting anisotropy parameters and different values of the most significant components of the g tensor. The predicted axial anisotropy D = -147.2 cm -1 for complex II is twice that observed experimentally for complex I, D = -72.8 cm -1 , suggesting that this complex may be of interest for practical applications. We also analyze the temperature dependence of the magnetic susceptibility and molar magnetization for these complexes when subject to an external magnetic field. Overall, our results suggest that o-carborane-incorporated Co(II) complexes are worthwhile candidates for experimental exploration as single-ion molecular magnets.

Constructing a starting 3D shear velocity model with sharp interfaces for SEM-based upper mantle tomography in North America

NASA Astrophysics Data System (ADS)

Calo, M.; Bodin, T.; Yuan, H.; Romanowicz, B. A.; Larmat, C. S.; Maceira, M.

2013-12-01

Seismic tomography is currently evolving towards 3D earth models that satisfy full seismic waveforms at increasingly high frequencies. This evolution is possible thanks to the advent of powerful numerical methods such as the Spectral Element Method (SEM) that allow accurate computation of the seismic wavefield in complex media, and the drastic increase of computational resources. However, the production of such models requires handling complex misfit functions with more than one local minimum. Standard linearized inversion methods (such as gradient methods) have two main drawbacks: 1) they produce solution models highly dependent on the starting model; 2) they do not provide a means of estimating true model uncertainties. However, these issues can be addressed with stochastic methods that can sample the space of possible solutions efficiently. Such methods are prohibitively challenging computationally in 3D, but increasingly accessible in 1D. In previous work (Yuan and Romanowicz, 2010; Yuan et al., 2011) we developed a continental scale anisotropic upper mantle model of north America based on a combination of long period seismic waveforms and SKS splitting measurements, showing the pervasive presence of layering of anisotropy in the cratonic lithosphere with significant variations in depth of the mid-lithospheric boundary. The radial anisotropy part of the model has been recently updated using the spectral element method for forward wavefield computations and waveform data from the latest deployments of USarray (Yuan and Romanowicz, 2013). However, the long period waveforms (periods > 40s) themselves only provide a relatively smooth view of the mantle if the starting model is smooth, and the mantle discontinuities necessary for geodynamical interpretation are not imaged. Increasing the frequency of the computations to constrain smaller scale features is possible, but challenging computationally, and at the risk of falling in local minima of the misfit function. In this work we propose instead to directly tackle the non-linearity of the inverse problem by using stochastic methods to construct a 3D starting model with a good estimate of the depths of the main layering interfaces. We present preliminary results of the construction of such a starting 3D model based on: (1) Regionalizing the study area to define provinces within which lateral variations are smooth; (2) Applying trans-dimensional stochastic inversion (Bodin et al., 2012) to obtain accurate 1D models in each province as well as the corresponding error distribution, constrained by receiver function and surface wave dispersion data as well as the previously constructed 3D model (name), and (3) connecting these models laterally using data-driven smoothing operators to obtain a starting 3D model with errors. References Bodin, T.,et al. 2012, Transdimensional inversion of receiver functions and surface wave dispersion, J. Geophys. Res., 117, B02301, doi:10.1029/2011JB008560. Yuan and Romanowicz, 2013, in revison. Yuan, H., et al. 2011, 3-D shear wave radially and azimuthally anisotropic velocity model of the North American upper mantle. Geophysical Journal International, 184: 1237-1260. doi: 10.1111/j.1365-246X.2010.04901.x Yuan, H. & Romanowicz, B., 2010. Lithospheric layering in the North American Craton, Nature, 466, 1063-1068.

Modelling Thin Film Microbending: A Comparative Study of Three Different Approaches

NASA Astrophysics Data System (ADS)

Aifantis, Katerina E.; Nikitas, Nikos; Zaiser, Michael

2011-09-01

Constitutive models which describe crystal microplasticity in a continuum framework can be envisaged as average representations of the dynamics of dislocation systems. Thus, their performance needs to be assessed not only by their ability to correctly represent stress-strain characteristics on the specimen scale but also by their ability to correctly represent the evolution of internal stress and strain patterns. In the present comparative study we consider the bending of a free-standing thin film. We compare the results of 3D DDD simulations with those obtained from a simple 1D gradient plasticity model and a more complex dislocation-based continuum model. Both models correctly reproduce the nontrivial strain patterns predicted by DDD for the microbending problem.

2D/3D image charge for modeling field emission

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

Jensen, Kevin L.; Shiffler, Donald A.; Harris, John R.

Analytic image charge approximations exist for planar and spherical metal surfaces but approximations for more complex geometries, such as the conical and wirelike structures characteristic of field emitters, are lacking. Such models are the basis for the evaluation of Schottky lowering factors in equations for current density. The development of a multidimensional image charge approximation, useful for a general thermal-field emission equation used in space charge studies, is given and based on an analytical model using a prolate spheroidal geometry. A description of how the model may be adapted to be used with a line charge model appropriate for carbonmore » nanotube and carbon fiber field emitters is discussed. [http://dx.doi.org/10.1116/1.4968007]« less

2D/3D image charge for modeling field emission

DOE PAGES

Jensen, Kevin L.; Shiffler, Donald A.; Harris, John R.; ...

2017-03-01

Analytic image charge approximations exist for planar and spherical metal surfaces but approximations for more complex geometries, such as the conical and wirelike structures characteristic of field emitters, are lacking. Such models are the basis for the evaluation of Schottky lowering factors in equations for current density. The development of a multidimensional image charge approximation, useful for a general thermal-field emission equation used in space charge studies, is given and based on an analytical model using a prolate spheroidal geometry. A description of how the model may be adapted to be used with a line charge model appropriate for carbonmore » nanotube and carbon fiber field emitters is discussed. [http://dx.doi.org/10.1116/1.4968007]« less

Ruthenium(II) bipyridine complexes bearing new keto-enol azoimine ligands: synthesis, structure, electrochemistry and DFT calculations.

PubMed

Al-Noaimi, Mousa; Awwadi, Firas F; Mansi, Ahmad; Abdel-Rahman, Obadah S; Hammoudeh, Ayman; Warad, Ismail

2015-01-25

The novel azoimine ligand, Ph-NH-N=C(COCH3)-NHPh(C≡CH) (H2L), was synthesized and its molecular structure was determined by X-ray crystallography. Catalytic hydration of the terminal acetylene of H2L in the presence of RuCl3·3H2O in ethanol at reflux temperature yielded a ketone (L1=Ph-N=N-C(COCH3)=N-Ph(COCH3) and an enol (L2=Ph-N=N-C(COCH3)=N-PhC(OH)=CH2) by Markovnikov addition of water. Two mixed-ligand ruthenium complexes having general formula, trans-[Ru(bpy)(Y)Cl2] (1-2) (where Y=L1 (1) and Y=L2 (2), bpy is 2.2'-bipyrdine) were achieved by the stepwise addition of equimolar amounts of (H2L) and bpy ligands to RuCl3·3H2O in absolute ethanol. Theses complexes were characterized by elemental analyses and spectroscopic (IR, UV-Vis, and NMR (1D (1)H NMR, (13)C NMR, (DEPT-135), (DEPT-90), 2D (1)H-(1)H and (13)C-(1)H correlation (HMQC) spectroscopy)). The two complexes exhibit a quasi-reversible one electron Ru(II)/Ru(III) oxidation couple at 604 mV vs. ferrocene/ferrocenium (Cp2Fe(0/+)) couple along with one electron ligand reduction at -1010 mV. The crystal structure of complex 1 showed that the bidentate ligand L1 coordinates to Ru(II) by the azo- and imine-nitrogen donor atoms. The complex adopts a distorted trans octahedral coordination geometry of chloride ligands. The electronic spectra of 1 and 1+ in dichloromethane have been modeled by time-dependent density functional theory (TD-DFT). Copyright © 2014 Elsevier B.V. All rights reserved.

Influence of Sulfolane on ESI-MS Measurements of Protein-Ligand Affinities

NASA Astrophysics Data System (ADS)

Yao, Yuyu; Richards, Michele R.; Kitova, Elena N.; Klassen, John S.

2016-03-01

The results of an investigation into the influence of sulfolane, a commonly used supercharging agent, on electrospray ionization mass spectrometry (ESI-MS) measurements of protein-ligand affinities are described. Binding measurements carried out on four protein-carbohydrate complexes, lysozyme with β- d-GlcNAc-(1→4)-β- d-GlcNAc-(1→4)-β- d-GlcNAc-(1→4)- d-GlcNAc, a single chain variable fragment and α- d-Gal-(1→2)-[α- d-Abe-(1→3)]-α- d-Man-OCH3, cholera toxin B subunit homopentamer with β- d-Gal-(1→3)-β- d-GalNAc-(1→4)[α- d-Neu5Ac-(2→3)]-β- d-Gal-(1→4)-β- d-Glc, and a fragment of galectin 3 and α- l-Fuc-(1→2)-β- d-Gal-(1→3)-β- d-GlcNAc-(1→3)-β- d-Gal-(1→4)-β- d-Glc, revealed that sulfolane generally reduces the apparent (as measured by ESI-MS) protein-ligand affinities. To establish the origin of this effect, a detailed study was undertaken using the lysozyme-tetrasaccharide interaction as a model system. Measurements carried out using isothermal titration calorimetry (ITC), circular dichroism, and nuclear magnetic resonance spectroscopies reveal that sulfolane reduces the binding affinity in solution but does not cause any significant change in the higher order structure of lysozyme or to the intermolecular interactions. These observations confirm that changes to the structure of lysozyme in bulk solution are not responsible for the supercharging effect induced by sulfolane. Moreover, the agreement between the ESI-MS and ITC-derived affinities indicates that there is no dissociation of the complex during ESI or in the gas phase (i.e., in-source dissociation). This finding suggests that supercharging of lysozyme by sulfolane is not related to protein unfolding during the ESI process. Binding measurements performed using liquid sample desorption ESI-MS revealed that protein supercharging with sulfolane can be achieved without a reduction in affinity.

Influence of Sulfolane on ESI-MS Measurements of Protein-Ligand Affinities.

PubMed

Yao, Yuyu; Richards, Michele R; Kitova, Elena N; Klassen, John S

2016-03-01

The results of an investigation into the influence of sulfolane, a commonly used supercharging agent, on electrospray ionization mass spectrometry (ESI-MS) measurements of protein-ligand affinities are described. Binding measurements carried out on four protein-carbohydrate complexes, lysozyme with β-D-GlcNAc-(1→4)-β-D-GlcNAc-(1→4)-β-D-GlcNAc-(1→4)-D-GlcNAc, a single chain variable fragment and α-D-Gal-(1→2)-[α-D-Abe-(1→3)]-α-D-Man-OCH3, cholera toxin B subunit homopentamer with β-D-Gal-(1→3)-β-D-GalNAc-(1→4)[α-D-Neu5Ac-(2→3)]-β-D-Gal-(1→4)-β-D-Glc, and a fragment of galectin 3 and α-L-Fuc-(1→2)-β-D-Gal-(1→3)-β-D-GlcNAc-(1→3)-β-D-Gal-(1→4)-β-D-Glc, revealed that sulfolane generally reduces the apparent (as measured by ESI-MS) protein-ligand affinities. To establish the origin of this effect, a detailed study was undertaken using the lysozyme-tetrasaccharide interaction as a model system. Measurements carried out using isothermal titration calorimetry (ITC), circular dichroism, and nuclear magnetic resonance spectroscopies reveal that sulfolane reduces the binding affinity in solution but does not cause any significant change in the higher order structure of lysozyme or to the intermolecular interactions. These observations confirm that changes to the structure of lysozyme in bulk solution are not responsible for the supercharging effect induced by sulfolane. Moreover, the agreement between the ESI-MS and ITC-derived affinities indicates that there is no dissociation of the complex during ESI or in the gas phase (i.e., in-source dissociation). This finding suggests that supercharging of lysozyme by sulfolane is not related to protein unfolding during the ESI process. Binding measurements performed using liquid sample desorption ESI-MS revealed that protein supercharging with sulfolane can be achieved without a reduction in affinity.

A Study on Spectro-Analytical Aspects, DNA - Interaction, Photo-Cleavage, Radical Scavenging, Cytotoxic Activities, Antibacterial and Docking Properties of 3 - (1 - (6 - methoxybenzo [d] thiazol - 2 - ylimino) ethyl) - 6 - methyl - 3H - pyran - 2, 4 - dione and its Metal Complexes.

PubMed

Ravi, Mudavath; Chennam, Kishan Prasad; Ushaiah, B; Eslavath, Ravi Kumar; Perugu, Shyam; Ajumeera, Rajanna; Devi, Ch Sarala

2015-09-01

The focus of the present work is on the design, synthesis, characterization, DNA-interaction, photo-cleavage, radical scavenging, in-vitro cytotoxicity, antimicrobial, docking and kinetic studies of Cu (II), Cd (II), Ce (IV) and Zr (IV) metal complexes of an imine derivative, 3 - (1 - (6 - methoxybenzo [d] thiazol - 2 - ylimino) ethyl) - 6 - methyl - 3H - pyran - 2, 4 - dione. The investigation of metal ligand interactions for the determination of composition of metal complexes, corresponding kinetic studies and antioxidant activity in solution was carried out by spectrophotometric methods. The synthesized metal complexes were characterized by EDX analysis, Mass, IR, (1)H-NMR, (13)C-NMR and UV-Visible spectra. DNA binding studies of metal complexes with Calf thymus (CT) DNA were carried out at room temperature by employing UV-Vis electron absorption, fluorescence emission and viscosity measurement techniques. The results revealed that these complexes interact with DNA through intercalation. The results of in vitro antibacterial studies showed the enhanced activity of chelating agent in metal chelated form and thus inferring scope for further development of new therapeutic drugs. Cell viability experiments indicated that all complexes showed significant dose dependent cytotoxicity in selected cell lines. The molecular modeling and docking studies were carried out with energy minimized structures of metal complexes to identify the receptor to metal interactions.

Spectral-spatial classification of hyperspectral image using three-dimensional convolution network

NASA Astrophysics Data System (ADS)

Liu, Bing; Yu, Xuchu; Zhang, Pengqiang; Tan, Xiong; Wang, Ruirui; Zhi, Lu

2018-01-01

Recently, hyperspectral image (HSI) classification has become a focus of research. However, the complex structure of an HSI makes feature extraction difficult to achieve. Most current methods build classifiers based on complex handcrafted features computed from the raw inputs. The design of an improved 3-D convolutional neural network (3D-CNN) model for HSI classification is described. This model extracts features from both the spectral and spatial dimensions through the application of 3-D convolutions, thereby capturing the important discrimination information encoded in multiple adjacent bands. The designed model views the HSI cube data altogether without relying on any pre- or postprocessing. In addition, the model is trained in an end-to-end fashion without any handcrafted features. The designed model was applied to three widely used HSI datasets. The experimental results demonstrate that the 3D-CNN-based method outperforms conventional methods even with limited labeled training samples.

The cranial nerve skywalk: A 3D tutorial of cranial nerves in a virtual platform.

PubMed

Richardson-Hatcher, April; Hazzard, Matthew; Ramirez-Yanez, German

2014-01-01

Visualization of the complex courses of the cranial nerves by students in the health-related professions is challenging through either diagrams in books or plastic models in the gross laboratory. Furthermore, dissection of the cranial nerves in the gross laboratory is an extremely meticulous task. Teaching and learning the cranial nerve pathways is difficult using two-dimensional (2D) illustrations alone. Three-dimensional (3D) models aid the teacher in describing intricate and complex anatomical structures and help students visualize them. The study of the cranial nerves can be supplemented with 3D, which permits the students to fully visualize their distribution within the craniofacial complex. This article describes the construction and usage of a virtual anatomy platform in Second Life™, which contains 3D models of the cranial nerves III, V, VII, and IX. The Cranial Nerve Skywalk features select cranial nerves and the associated autonomic pathways in an immersive online environment. This teaching supplement was introduced to groups of pre-healthcare professional students in gross anatomy courses at both institutions and student feedback is included. © 2014 American Association of Anatomists.

AxiSEM3D: broadband seismic wavefields in 3-D aspherical Earth models

NASA Astrophysics Data System (ADS)

Leng, K.; Nissen-Meyer, T.; Zad, K. H.; van Driel, M.; Al-Attar, D.

2017-12-01

Seismology is the primary tool for data-informed inference of Earth structure and dynamics. Simulating seismic wave propagation at a global scale is fundamental to seismology, but remains as one of most challenging problems in scientific computing, because of both the multiscale nature of Earth's interior and the observable frequency band of seismic data. We present a novel numerical method to simulate global seismic wave propagation in realistic 3-D Earth models. Our method, named AxiSEM3D, is a hybrid of spectral element method and pseudospectral method. It reduces the azimuthal dimension of wavefields by means of a global Fourier series parameterization, of which the number of terms can be locally adapted to the inherent azimuthal smoothness of the wavefields. AxiSEM3D allows not only for material heterogeneities, such as velocity, density, anisotropy and attenuation, but also for finite undulations on radial discontinuities, both solid-solid and solid-fluid, and thereby a variety of aspherical Earth features such as ellipticity, topography, variable crustal thickness, and core-mantle boundary topography. Such interface undulations are equivalently interpreted as material perturbations of the contiguous media, based on the "particle relabelling transformation". Efficiency comparisons show that AxiSEM3D can be 1 to 3 orders of magnitude faster than conventional 3-D methods, with the speedup increasing with simulation frequency and decreasing with model complexity, but for all realistic structures the speedup remains at least one order of magnitude. The observable frequency range of global seismic data (up to 1 Hz) has been covered for wavefield modelling upon a 3-D Earth model with reasonable computing resources. We show an application of surface wave modelling within a state-of-the-art global crustal model (Crust1.0), with the synthetics compared to real data. The high-performance C++ code is released at github.com/AxiSEM3D/AxiSEM3D.

Modeling and Docking Studies on Novel Mutants (K71L and T204V) of the ATPase Domain of Human Heat Shock 70 kDa Protein 1

PubMed Central

Elengoe, Asita; Naser, Mohammed Abu; Hamdan, Salehhuddin

2014-01-01

The purpose of exploring protein interactions between human adenovirus and heat shock protein 70 is to exploit a potentially synergistic interaction to enhance anti-tumoral efficacy and decrease toxicity in cancer treatment. However, the protein interaction of Hsp70 with E1A32 kDa of human adenovirus serotype 5 remains to be elucidated. In this study, two residues of ATPase domain of human heat shock 70 kDa protein 1 (PDB: 1 HJO) were mutated. 3D mutant models (K71L and T204V) using PyMol software were then constructed. The structures were evaluated by PROCHECK, ProQ, ERRAT, Verify 3D and ProSA modules. All evidence suggests that all protein models are acceptable and of good quality. The E1A32 kDa motif was retrieved from UniProt (P03255), as well as subjected to docking interaction with NBD, K71L and T204V, using the Autodock 4.2 program. The best lowest binding energy value of −9.09 kcal/mol was selected for novel T204V. Moreover, the protein-ligand complex structures were validated by RMSD, RMSF, hydrogen bonds and salt bridge analysis. This revealed that the T204V-E1A32 kDa motif complex was the most stable among all three complex structures. This study provides information about the interaction between Hsp70 and the E1A32 kDa motif, which emphasizes future perspectives to design rational drugs and vaccines in cancer therapy. PMID:24758925

3D-Printing in Congenital Cardiology: From Flatland to Spaceland.

PubMed

Deferm, Sébastien; Meyns, Bart; Vlasselaers, Dirk; Budts, Werner

2016-01-01

Medical imaging has changed to a great extent over the past few decades. It has been revolutionized by three-dimensional (3D) imaging techniques. Despite much of modern medicine relying on 3D imaging, which can be obtained accurately, we keep on being limited by visualization of the 3D content on two-dimensional flat screens. 3D-printing of graspable models could become a feasible technique to overcome this gap. Therefore, we printed pre- and postoperative 3D-models of a complex congenital heart defect. With this example, we intend to illustrate that these models hold value in preoperative planning, postoperative evaluation of a complex procedure, communication with the patient, and education of trainees. At this moment, 3D printing only leaves a small footprint, but makes already a big impression in the domain of cardiology and cardiovascular surgery. Further studies including more patients and more validated applications are needed to streamline 3D printing in the clinical setting of daily practice.

Self-assembled 1D infinite inorganic [2]catenane and 2D sheet framework with calix[8]phenylazoimidazole and [4+4]metallomacrocyclic motifs based on silver and ditopic bis(imidazolyl)methane ligands

NASA Astrophysics Data System (ADS)

Jin, Tianqi; Zhou, Junqiang; Pan, Yangyang; Huang, Yu; Jin, Chuanming

2018-05-01

Three novel supramolecular complexes, [Ag4(2-mBIM)4](ClO4)4(H2O) (1), [Ag2(2-mBIM)2](PF6)2 (2) and [Ag2(PA-BIM)2](ClO4)2(CH2Cl2) (3) (2-mBIM = bis(2-methyl- imidazol-1-yl)methane; PA-BIM = 1,1-bis[(2-phenylazo)imidazol-1-yl]methane), have been prepared and structurally characterized. The reported complexes bear [4+4]metallomacrocyclic motifs comprising four silver atoms and four ditopic bis(imidazolyl)methane ligands. Complex 1 exhibits a rare 1D infinite inorganic [2]catenane structure, which was self-assembled by the interlocking action of [4+4]metallomacrocyclic units. Complex 2 is a 2D layered supramolecular motif containing [4+4]macrometallacycle units with π-π interaction between imidazole rings. Complex 3 has a 2D sheet supramolecular framework through Ag-Ag interactions in [4+4]macrometallacyclic calix [8]phenylazoimidazole with a nanocavity. The results suggest that the bisimidazolium ligands and anions play crucial roles in the formation of the different host structures. The thermal stability and photoluminescence spectra of the synthesized complexes have also been discussed.

Structural and Functional Analysis of Sulfolobus solfataricus Y-Family DNA Polymerase Dpo4-Catalyzed Bypass of the Malondialdehyde−Deoxyguanosine Adduct

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

Eoff, Robert L.; Stafford, Jennifer B.; Szekely, Jozsef

2010-01-12

Oxidative stress can induce the formation of reactive electrophiles, such as DNA peroxidation products, e.g., base propenals, and lipid peroxidation products, e.g., malondialdehyde. Base propenals and malondialdehyde react with DNA to form adducts, including 3-(2'-deoxy-{beta}-d-erythro-pentofuranosyl)pyrimido[1,2-{alpha}]purin-10(3H)-one (M{sub 1}dG). When paired opposite cytosine in duplex DNA at physiological pH, M{sub 1}dG undergoes ring opening to form N{sup 2}-(3-oxo-1-propenyl)-dG (N{sup 2}-OPdG). Previous work has shown that M{sub 1}dG is mutagenic in bacteria and mammalian cells and that its mutagenicity in Escherichia coli is dependent on induction of the SOS response, indicating a role for translesion DNA polymerases in the bypass of M{sub 1}dG.more » To probe the mechanism by which translesion polymerases bypass M{sub 1}dG, kinetic and structural studies were conducted with a model Y-family DNA polymerase, Dpo4 from Sulfolobus solfataricus. The level of steady-state incorporation of dNTPs opposite M{sub 1}dG was reduced 260-2900-fold and exhibited a preference for dATP incorporation. Liquid chromatography-tandem mass spectrometry analysis of the full-length extension products revealed a spectrum of products arising principally by incorporation of dC or dA opposite M{sub 1}dG followed by partial or full-length extension. A greater proportion of -1 deletions were observed when dT was positioned 5' of M{sub 1}dG. Two crystal structures were determined, including a 'type II' frameshift deletion complex and another complex with Dpo4 bound to a dC-M{sub 1}dG pair located in the postinsertion context. Importantly, M{sub 1}dG was in the ring-closed state in both structures, and in the structure with dC opposite M{sub 1}dG, the dC residue moved out of the Dpo4 active site, into the minor groove. The results are consistent with the reported mutagenicity of M{sub 1}dG and illustrate how the lesion may affect replication events.« less

Rogue-wave bullets in a composite (2+1)D nonlinear medium.

PubMed

Chen, Shihua; Soto-Crespo, Jose M; Baronio, Fabio; Grelu, Philippe; Mihalache, Dumitru

2016-07-11

We show that nonlinear wave packets localized in two dimensions with characteristic rogue wave profiles can propagate in a third dimension with significant stability. This unique behavior makes these waves analogous to light bullets, with the additional feature that they propagate on a finite background. Bulletlike rogue-wave singlet and triplet are derived analytically from a composite (2+1)D nonlinear wave equation. The latter can be interpreted as the combination of two integrable (1+1)D models expressed in different dimensions, namely, the Hirota equation and the complex modified Korteweg-de Vries equation. Numerical simulations confirm that the generation of rogue-wave bullets can be observed in the presence of spontaneous modulation instability activated by quantum noise.

Numerical simulation of deformation and failure processes of a complex technical object under impact loading

NASA Astrophysics Data System (ADS)

Kraus, E. I.; Shabalin, I. I.; Shabalin, T. I.

2018-04-01

The main points of development of numerical tools for simulation of deformation and failure of complex technical objects under nonstationary conditions of extreme loading are presented. The possibility of extending the dynamic method for construction of difference grids to the 3D case is shown. A 3D realization of discrete-continuum approach to the deformation and failure of complex technical objects is carried out. The efficiency of the existing software package for 3D modelling is shown.

Complex bilobular, bisaccular, and broad-neck microsurgical aneurysm formation in the rabbit bifurcation model for the study of upcoming endovascular techniques.

PubMed

Marbacher, S; Erhardt, S; Schläppi, J-A; Coluccia, D; Remonda, L; Fandino, J; Sherif, C

2011-04-01

Despite rapid advances in the development of materials and techniques for endovascular intracranial aneurysm treatment, occlusion of large broad-neck aneurysms remains a challenge. Animal models featuring complex aneurysm architecture are needed to test endovascular innovations and train interventionalists. Eleven adult female New Zealand rabbits were assigned to 3 experimental groups. Complex bilobular, bisaccular, and broad-neck venous pouch aneurysms were surgically formed at an artificially created bifurcation of both CCAs. Three and 5 weeks postoperatively, the rabbits underwent 2D-DSA and CE-3D-MRA, respectively. Mortality was 0%. We observed no neurologic, respiratory, or gastrointestinal complications. The aneurysm patency rate was 91% (1 aneurysm thrombosis). There was 1 postoperative aneurysm hemorrhage (9% morbidity). The mean aneurysm volumes were 176.9 ± 63.6 mm(3), 298.6 ± 75.2 mm(3), and 183.4 ± 72.4 mm(3) in bilobular, bisaccular, and broad-neck aneurysms, respectively. The mean operation time was 245 minutes (range, 175-290 minutes). An average of 27 ± 4 interrupted sutures (range, 21-32) were needed to create the aneurysms. This study demonstrates the feasibility of creating complex venous pouch bifurcation aneurysms in the rabbit with low morbidity, mortality, and high short-term aneurysm patency. The necks, domes, and volumes of the bilobular, bisaccular, and broad-neck aneurysms created are larger than those previously described. These new complex aneurysm formations are a promising tool for in vivo animal testing of new endovascular devices.

A Corner-Point-Grid-Based Voxelization Method for Complex Geological Structure Model with Folds

NASA Astrophysics Data System (ADS)

Chen, Qiyu; Mariethoz, Gregoire; Liu, Gang

2017-04-01

3D voxelization is the foundation of geological property modeling, and is also an effective approach to realize the 3D visualization of the heterogeneous attributes in geological structures. The corner-point grid is a representative data model among all voxel models, and is a structured grid type that is widely applied at present. When carrying out subdivision for complex geological structure model with folds, we should fully consider its structural morphology and bedding features to make the generated voxels keep its original morphology. And on the basis of which, they can depict the detailed bedding features and the spatial heterogeneity of the internal attributes. In order to solve the shortage of the existing technologies, this work puts forward a corner-point-grid-based voxelization method for complex geological structure model with folds. We have realized the fast conversion from the 3D geological structure model to the fine voxel model according to the rule of isocline in Ramsay's fold classification. In addition, the voxel model conforms to the spatial features of folds, pinch-out and other complex geological structures, and the voxels of the laminas inside a fold accords with the result of geological sedimentation and tectonic movement. This will provide a carrier and model foundation for the subsequent attribute assignment as well as the quantitative analysis and evaluation based on the spatial voxels. Ultimately, we use examples and the contrastive analysis between the examples and the Ramsay's description of isoclines to discuss the effectiveness and advantages of the method proposed in this work when dealing with the voxelization of 3D geologic structural model with folds based on corner-point grids.

Calibration of Two-dimensional Floodplain Modeling in the Atchafalaya River Basin Using SAR Interferometry

NASA Technical Reports Server (NTRS)

Jung, Hahn Chul; Jasinski, Michael; Kim, Jin-Woo; Shum, C. K.; Bates, Paul; Lee, Hgongki; Neal, Jeffrey; Alsdorf, Doug

2012-01-01

Two-dimensional (2D) satellite imagery has been increasingly employed to improve prediction of floodplain inundation models. However, most focus has been on validation of inundation extent, with little attention on the 2D spatial variations of water elevation and slope. The availability of high resolution Interferometric Synthetic Aperture Radar (InSAR) imagery offers unprecedented opportunity for quantitative validation of surface water heights and slopes derived from 2D hydrodynamic models. In this study, the LISFLOOD-ACC hydrodynamic model is applied to the central Atchafalaya River Basin, Louisiana, during high flows typical of spring floods in the Mississippi Delta region, for the purpose of demonstrating the utility of InSAR in coupled 1D/2D model calibration. Two calibration schemes focusing on Manning s roughness are compared. First, the model is calibrated in terms of water elevations at a single in situ gage during a 62 day simulation period from 1 April 2008 to 1 June 2008. Second, the model is calibrated in terms of water elevation changes calculated from ALOS PALSAR interferometry during 46 days of the image acquisition interval from 16 April 2008 to 1 June 2009. The best-fit models show that the mean absolute errors are 3.8 cm for a single in situ gage calibration and 5.7 cm/46 days for InSAR water level calibration. The optimum values of Manning's roughness coefficients are 0.024/0.10 for the channel/floodplain, respectively, using a single in situ gage, and 0.028/0.10 for channel/floodplain the using SAR. Based on the calibrated water elevation changes, daily storage changes within the size of approx 230 sq km of the model area are also calculated to be of the order of 107 cubic m/day during high water of the modeled period. This study demonstrates the feasibility of SAR interferometry to support 2D hydrodynamic model calibration and as a tool for improved understanding of complex floodplain hydrodynamics

Predictive Engineering Tools for Injection-Molded Long-Carbon-Fiber Thermoplastic Composites. Topical Report

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

Nguyen, Ba Nghiep; Fifield, Leonard S.; Wang, Jin

2016-06-01

This project aimed to integrate, optimize, and validate the fiber orientation and length distribution models previously developed and implemented in the Autodesk® Simulation Moldflow® Insight (ASMI) software package for injection-molded long-carbon-fiber (LCF) thermoplastic composite structures. The project was organized into two phases. Phase 1 demonstrated the ability of the advanced ASMI package to predict fiber orientation and length distributions in LCF/polypropylene (PP) and LCF/polyamide-6, 6 (PA66) plaques within 15% of experimental results. Phase 2 validated the advanced ASMI package by predicting fiber orientation and length distributions within 15% of experimental results for a complex three-dimensional (3D) Toyota automotive part injection-moldedmore » from LCF/PP and LCF/PA66 materials. Work under Phase 2 also included estimate of weight savings and cost impacts for a vehicle system using ASMI and structural analyses of the complex part. The present report summarizes the completion of Phases 1 and 2 work activities and accomplishments achieved by the team comprising Pacific Northwest National Laboratory (PNNL); Purdue University (Purdue); Virginia Polytechnic Institute and State University (Virginia Tech); Autodesk, Inc. (Autodesk); PlastiComp, Inc. (PlastiComp); Toyota Research Institute North America (Toyota); Magna Exteriors and Interiors Corp. (Magna); and University of Illinois. Figure 1 illustrates the technical approach adopted in this project that progressed from compounding LCF/PP and LCF/PA66 materials, to process model improvement and implementation, to molding and modeling LCF/PP and LCF/PA66 plaques. The lessons learned from the plaque study and the successful validation of improved process models for fiber orientation and length distributions for these plaques enabled the project to go to Phase 2 to mold, model, and optimize the 3D complex part.« less

Investigating vibrational anharmonic couplings in cyanide-bridged transition metal mixed valence complexes using two-dimensional infrared spectroscopy.

PubMed

Slenkamp, Karla M; Lynch, Michael S; Van Kuiken, Benjamin E; Brookes, Jennifer F; Bannan, Caitlin C; Daifuku, Stephanie L; Khalil, Munira

2014-02-28

Using polarization-selective two-dimensional infrared (2D IR) spectroscopy, we measure anharmonic couplings and angles between the transition dipole moments of the four cyanide stretching (νCN) vibrations found in [(NH3)5Ru(III)NCFe(II)(CN)5](-) (FeRu) dissolved in D2O and formamide and [(NC)5Fe(II)CNPt(IV)(NH3)4NCFe(II)(CN)5](4-) (FePtFe) dissolved in D2O. These cyanide-bridged transition metal complexes serve as model systems for studying the role of high frequency vibrational modes in ultrafast photoinduced charge transfer reactions. Here, we focus on the spectroscopy of the νCN modes in the electronic ground state. The FTIR spectra of the νCN modes of the bimetallic and trimetallic systems are strikingly different in terms of frequencies, amplitudes, and lineshapes. The experimental 2D IR spectra of FeRu and FePtFe and their fits reveal a set of weakly coupled anharmonic νCN modes. The vibrational mode anharmonicities of the individual νCN modes range from 14 to 28 cm(-1). The mixed-mode anharmonicities range from 2 to 14 cm(-1). In general, the bridging νCN mode is most weakly coupled to the radial νCN mode, which involves the terminal CN ligands. Measurement of the relative transition dipole moments of the four νCN modes reveal that the FeRu molecule is almost linear in solution when dissolved in formamide, but it assumes a bent geometry when dissolved in D2O. The νCN modes are modelled as bilinearly coupled anharmonic oscillators with an average coupling constant of 6 cm(-1). This study elucidates the role of the solvent in modulating the molecular geometry and the anharmonic vibrational couplings between the νCN modes in cyanide-bridged transition metal mixed valence complexes.

Crystal structures of resorcin[4]arene and pyrogallol[4]arene complexes with DL-pipecolinic acid. Model compounds for the recognition of the pipecolinyl ring, a key fragment of FK506, through C-H⋯π interaction

NASA Astrophysics Data System (ADS)

Fujisawa, Ikuhide; Kitamura, Yuji; Kato, Ryo; Murayama, Kazutaka; Aoki, Katsuyuki

2014-01-01

Resorcin[4]arene (resorcinol cyclic tetramer, abbreviated as RCT) or pyrogallol[4]arene (pyrogallol cyclic tetramer, PCT) form host-guest 1:1 complexes with DL-pipecolinic acid (DL-pipeH), RCT·DL-pipeH·EtOH·8H2O (1), PCT DL-pipeH·EtOH·4H2O (2), and PCT·DL-pipeH·3H2O (3), whose crystal structures have been determined. In each complex, the pipeH ligand is incorporated into the bowl-shaped cavity of the RCT or PCT host molecules through C-H⋯π interactions between alkyl protons of the piperidine ring of pipeH and π-rings of RCT or PCT, forming an [(RCT/PCT)·pipeH] structural fragment. In 1 and 3, two [(RCT/PCT) pipeH] fragments self-associate across an inversion center to form a guest-mediated, obliquely declined dimeric structure [(RCT/PCT)·L-pipeH·D-pipeH (RCT/PCT)]. In 2, each PCT-capped pipeH ligand bridges to two adjacent PCT molecules to form guest-mediated, optically-discrete helical polymers [PCT·L-pipeH]n or [PCT·D-pipeH]n. An 1H NMR experiment shows that the complexation through C-H⋯π interaction between the piperidine ring of pipeH and π-rings of RCT or PCT occurs also in solution, with the binding constants of 9.7 ± 0.6 M-1 for RCT and 26.5 ± 1.5 M-1 for PCT. These complexes provide a synthetic model for the recognition of the pipecolinyl-ring moiety, a key constituent of immunosuppressant drugs such as FK506, FK520 or rapamycin, by their binding proteins through C-H⋯π interaction.

3-D numerical simulations of earthquake ground motion in sedimentary basins: testing accuracy through stringent models

NASA Astrophysics Data System (ADS)

Chaljub, Emmanuel; Maufroy, Emeline; Moczo, Peter; Kristek, Jozef; Hollender, Fabrice; Bard, Pierre-Yves; Priolo, Enrico; Klin, Peter; de Martin, Florent; Zhang, Zhenguo; Zhang, Wei; Chen, Xiaofei

2015-04-01

Differences between 3-D numerical predictions of earthquake ground motion in the Mygdonian basin near Thessaloniki, Greece, led us to define four canonical stringent models derived from the complex realistic 3-D model of the Mygdonian basin. Sediments atop an elastic bedrock are modelled in the 1D-sharp and 1D-smooth models using three homogeneous layers and smooth velocity distribution, respectively. The 2D-sharp and 2D-smooth models are extensions of the 1-D models to an asymmetric sedimentary valley. In all cases, 3-D wavefields include strongly dispersive surface waves in the sediments. We compared simulations by the Fourier pseudo-spectral method (FPSM), the Legendre spectral-element method (SEM) and two formulations of the finite-difference method (FDM-S and FDM-C) up to 4 Hz. The accuracy of individual solutions and level of agreement between solutions vary with type of seismic waves and depend on the smoothness of the velocity model. The level of accuracy is high for the body waves in all solutions. However, it strongly depends on the discrete representation of the material interfaces (at which material parameters change discontinuously) for the surface waves in the sharp models. An improper discrete representation of the interfaces can cause inaccurate numerical modelling of surface waves. For all the numerical methods considered, except SEM with mesh of elements following the interfaces, a proper implementation of interfaces requires definition of an effective medium consistent with the interface boundary conditions. An orthorhombic effective medium is shown to significantly improve accuracy and preserve the computational efficiency of modelling. The conclusions drawn from the analysis of the results of the canonical cases greatly help to explain differences between numerical predictions of ground motion in realistic models of the Mygdonian basin. We recommend that any numerical method and code that is intended for numerical prediction of earthquake ground motion should be verified through stringent models that would make it possible to test the most important aspects of accuracy.

CarD stabilizes mycobacterial open complexes via a two-tiered kinetic mechanism

PubMed Central

Rammohan, Jayan; Ruiz Manzano, Ana; Garner, Ashley L.; Stallings, Christina L.; Galburt, Eric A.

2015-01-01

CarD is an essential and global transcriptional regulator in mycobacteria. While its biological role is unclear, CarD functions by interacting directly with RNA polymerase (RNAP) holoenzyme promoter complexes. Here, using a fluorescent reporter of open complex, we quantitate RPo formation in real time and show that Mycobacterium tuberculosis CarD has a dramatic effect on the energetics of RNAP bound complexes on the M. tuberculosis rrnAP3 ribosomal RNA promoter. The data reveal that Mycobacterium bovis RNAP exhibits an unstable RPo that is stabilized by CarD and suggest that CarD uses a two-tiered, concentration-dependent mechanism by associating with open and closed complexes with different affinities. Specifically, the kinetics of open-complex formation can be explained by a model where, at saturating concentrations of CarD, the rate of bubble collapse is slowed and the rate of opening is accelerated. The kinetics and open-complex stabilities of CarD mutants further clarify the roles played by the key residues W85, K90 and R25 previously shown to affect CarD-dependent gene regulation in vivo. In contrast to M. bovis RNAP, Escherichia coli RNAP efficiently forms RPo on rrnAP3, suggesting an important difference between the polymerases themselves and highlighting how transcriptional machinery can vary across bacterial genera. PMID:25697505

Integrating surrogate models into subsurface simulation framework allows computation of complex reactive transport scenarios

NASA Astrophysics Data System (ADS)

De Lucia, Marco; Kempka, Thomas; Jatnieks, Janis; Kühn, Michael

2017-04-01

Reactive transport simulations - where geochemical reactions are coupled with hydrodynamic transport of reactants - are extremely time consuming and suffer from significant numerical issues. Given the high uncertainties inherently associated with the geochemical models, which also constitute the major computational bottleneck, such requirements may seem inappropriate and probably constitute the main limitation for their wide application. A promising way to ease and speed-up such coupled simulations is achievable employing statistical surrogates instead of "full-physics" geochemical models [1]. Data-driven surrogates are reduced models obtained on a set of pre-calculated "full physics" simulations, capturing their principal features while being extremely fast to compute. Model reduction of course comes at price of a precision loss; however, this appears justified in presence of large uncertainties regarding the parametrization of geochemical processes. This contribution illustrates the integration of surrogates into the flexible simulation framework currently being developed by the authors' research group [2]. The high level language of choice for obtaining and dealing with surrogate models is R, which profits from state-of-the-art methods for statistical analysis of large simulations ensembles. A stand-alone advective mass transport module was furthermore developed in order to add such capability to any multiphase finite volume hydrodynamic simulator within the simulation framework. We present 2D and 3D case studies benchmarking the performance of surrogates and "full physics" chemistry in scenarios pertaining the assessment of geological subsurface utilization. [1] Jatnieks, J., De Lucia, M., Dransch, D., Sips, M.: "Data-driven surrogate model approach for improving the performance of reactive transport simulations.", Energy Procedia 97, 2016, p. 447-453. [2] Kempka, T., Nakaten, B., De Lucia, M., Nakaten, N., Otto, C., Pohl, M., Chabab [Tillner], E., Kühn, M.: "Flexible Simulation Framework to Couple Processes in Complex 3D Models for Subsurface Utilization Assessment.", Energy Procedia, 97, 2016 p. 494-501.

3D-QSAR (CoMFA, CoMSIA), molecular docking and molecular dynamics simulations study of 6-aryl-5-cyano-pyrimidine derivatives to explore the structure requirements of LSD1 inhibitors.

PubMed

Ding, Lina; Wang, Zhi-Zheng; Sun, Xu-Dong; Yang, Jing; Ma, Chao-Ya; Li, Wen; Liu, Hong-Min

2017-08-01

Recently, Histone Lysine Specific Demethylase 1 (LSD1) was regarded as a promising anticancer target for the novel drug discovery. And several small molecules as LSD1 inhibitors in different structures have been reported. In this work, we carried out a molecular modeling study on the 6-aryl-5-cyano-pyrimidine fragment LSD1 inhibitors using three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamics simulations. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used to generate 3D-QSAR models. The results show that the best CoMFA model has q 2 =0.802, r 2 ncv =0.979, and the best CoMSIA model has q 2 =0.799, r 2 ncv =0.982. The electrostatic, hydrophobic and H-bond donor fields play important roles in the models. Molecular docking studies predict the binding mode and the interactions between the ligand and the receptor protein. Molecular dynamics simulations results reveal that the complex of the ligand and the receptor protein are stable at 300K. All the results can provide us more useful information for our further drug design. Copyright © 2017. Published by Elsevier Ltd.

Understanding the physical basis of the salt dependence of the electrostatic binding free energy of mutated charged ligand-nucleic acid complexes.

PubMed

Harris, Robert C; Bredenberg, Johan H; Silalahi, Alexander R J; Boschitsch, Alexander H; Fenley, Marcia O

2011-06-01

The predictions of the derivative of the electrostatic binding free energy of a biomolecular complex, ΔG(el), with respect to the logarithm of the 1:1 salt concentration, d(ΔG(el))/d(ln[NaCl]), SK, by the Poisson-Boltzmann equation, PBE, are very similar to those of the simpler Debye-Hückel equation, DHE, because the terms in the PBE's predictions of SK that depend on the details of the dielectric interface are small compared to the contributions from long-range electrostatic interactions. These facts allow one to obtain predictions of SK using a simplified charge model along with the DHE that are highly correlated with both the PBE and experimental binding data. The DHE-based model developed here, which was derived from the generalized Born model, explains the lack of correlation between SK and ΔG(el) in the presence of a dielectric discontinuity, which conflicts with the popular use of this supposed correlation to parse experimental binding free energies into electrostatic and nonelectrostatic components. Moreover, the DHE model also provides a clear justification for the correlations between SK and various empirical quantities, like the number of ion pairs, the ligand charge on the interface, the Coulomb binding free energy, and the product of the charges on the complex's components, but these correlations are weak, questioning their usefulness. Copyright © 2011 Elsevier B.V. All rights reserved.

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

PubMed Central

Christakos, Sylvia; Dhawan, Puneet; Verstuyf, Annemieke; Verlinden, Lieve; Carmeliet, Geert

2016-01-01

1,25-Dihydroxvitamin D3 [1,25(OH)2D3] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH)2D3 action involves the direct binding of the 1,25(OH)2D3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH)2D3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH)2D3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease. PMID:26681795

DNA vaccines expressing soluble CD4-envelope proteins fused to C3d elicit cross-reactive neutralizing antibodies to HIV-1.

PubMed

Bower, Joseph F; Green, Thomas D; Ross, Ted M

2004-10-25

DNA vaccines expressing the envelope (Env) of the human immunodeficiency virus type 1 (HIV-1) have been relatively ineffective at generating high-titer, long-lasting, neutralizing antibodies in a variety of animal models. In this study, DNA vaccines were constructed to express a fusion protein of the soluble human CD4 (sCD4) and the gp120 subunit of the HIV-1 envelope. To enhance the immunogenicity of the expressed fusion protein, three copies of the murine C3d (mC3d3) were added to the carboxyl terminus of the complex. Monoclonal antibodies that recognize CD4-induced epitopes on gp120 efficiently bound to sCD4-gp120 or sCD4-gp120-mC3d3. In addition, both sCD4-gp120 and sCD4-gp120-mC3d3 bound to cells expressing appropriate coreceptors in the absence of cell surface hCD4. Mice (BALB/c) vaccinated with DNA vaccines expressing either gp120-mC3d3 or sCD4-gp120-mC3d3 elicited antibodies that neutralized homologous virus infection. However, the use of sCD4-gp120-mC3d3-DNA elicited the highest titers of neutralizing antibodies that persisted after depletion of anti-hCD4 antibodies. Interestingly, only mice vaccinated with DNA expressing sCD4-gp120-mC3d3 had antibodies that elicited cross-protective neutralizing antibodies. The fusion of sCD4 to the HIV-1 envelope exposes neutralizing epitopes that elicit broad protective immunity when the fusion complex is coupled with the molecular adjuvant, C3d.

Dopamine D2 heteroreceptor complexes and their receptor-receptor interactions in ventral striatum: novel targets for antipsychotic drugs.

PubMed

Fuxe, Kjell; Borroto-Escuela, Dasiel O; Tarakanov, Alexander O; Romero-Fernandez, Wilber; Ferraro, Luca; Tanganelli, Sergio; Perez-Alea, Mileidys; Di Palma, Michael; Agnati, Luigi F

2014-01-01

This review is focused on the D2 heteroreceptor complexes within the ventral striatum with their receptor-receptor interactions and relevance for the treatment of schizophrenia. A "guide-and-clasp" manner for receptor-receptor interactions is proposed where "adhesive guides" may be amino acid triplet homologies, which were determined for different kinds of D2 heteroreceptor complexes. The first putative D2 heteroreceptor complex to be discovered in relation to schizophrenia was the A2A-D2 heteroreceptor complex where antagonistic A2A-D2 receptor-receptor interactions were demonstrated after A2A agonist treatment in the ventral striatum. The A2A agonist CGS 21680 with atypical antipsychotic properties may at least in part act by increasing β-arrestin2 signaling over the D2 protomer in the A2A-D2 heteroreceptor complex in the ventral striatum. The antagonistic NTS1-D2 interactions in the NTS1-D2 heteroreceptor complex in the ventral striatum are proposed as one molecular mechanism for the potential antipsychotic effects of NT. Indications were obtained that the psychotic actions of the 5-HT2AR hallucinogens LSD and DOI can involve enhancement of D2R protomer signaling via a biased agonist action at the 5-HT2A protomer in the D2-5-HT2A heteroreceptor complex in the ventral striatum. Facilitatory allosteric D2likeR-OTR interactions in heteroreceptor complexes in nucleus accumbens may have a role in social and emotional behaviors. By blocking the D2 protomers of these heteroreceptor complexes, antipsychotics can fail to reduce the negative symptoms of schizophrenia. The discovery of different types of D2 heteroreceptor complexes gives an increased understanding of molecular mechanisms involved in causing schizophrenia and new strategies for its treatment and understanding the side effects of antipsychotics. © 2014 Elsevier B.V. All rights reserved.

A simple inertial formulation of the shallow water equations for efficient two-dimensional flood inundation modelling

NASA Astrophysics Data System (ADS)

Bates, Paul D.; Horritt, Matthew S.; Fewtrell, Timothy J.

2010-06-01

SummaryThis paper describes the development of a new set of equations derived from 1D shallow water theory for use in 2D storage cell inundation models where flows in the x and y Cartesian directions are decoupled. The new equation set is designed to be solved explicitly at very low computational cost, and is here tested against a suite of four test cases of increasing complexity. In each case the predicted water depths compare favourably to analytical solutions or to simulation results from the diffusive storage cell code of Hunter et al. (2005). For the most complex test involving the fine spatial resolution simulation of flow in a topographically complex urban area the Root Mean Squared Difference between the new formulation and the model of Hunter et al. is ˜1 cm. However, unlike diffusive storage cell codes where the stable time step scales with (1/Δ x) 2, the new equation set developed here represents shallow water wave propagation and so the stability is controlled by the Courant-Freidrichs-Lewy condition such that the stable time step instead scales with 1/Δ x. This allows use of a stable time step that is 1-3 orders of magnitude greater for typical cell sizes than that possible with diffusive storage cell models and results in commensurate reductions in model run times. For the tests reported in this paper the maximum speed up achieved over a diffusive storage cell model was 1120×, although the actual value seen will depend on model resolution and water surface gradient. Solutions using the new equation set are shown to be grid-independent for the conditions considered and to have an intuitively correct sensitivity to friction, however small instabilities and increased errors on predicted depth were noted when Manning's n = 0.01. The new equations are likely to find widespread application in many types of flood inundation modelling and should provide a useful additional tool, alongside more established model formulations, for a variety of flood risk management studies.

A 3D modeling approach to complex faults with multi-source data

NASA Astrophysics Data System (ADS)

Wu, Qiang; Xu, Hua; Zou, Xukai; Lei, Hongzhuan

2015-04-01

Fault modeling is a very important step in making an accurate and reliable 3D geological model. Typical existing methods demand enough fault data to be able to construct complex fault models, however, it is well known that the available fault data are generally sparse and undersampled. In this paper, we propose a workflow of fault modeling, which can integrate multi-source data to construct fault models. For the faults that are not modeled with these data, especially small-scale or approximately parallel with the sections, we propose the fault deduction method to infer the hanging wall and footwall lines after displacement calculation. Moreover, using the fault cutting algorithm can supplement the available fault points on the location where faults cut each other. Increasing fault points in poor sample areas can not only efficiently construct fault models, but also reduce manual intervention. By using a fault-based interpolation and remeshing the horizons, an accurate 3D geological model can be constructed. The method can naturally simulate geological structures no matter whether the available geological data are sufficient or not. A concrete example of using the method in Tangshan, China, shows that the method can be applied to broad and complex geological areas.

Comparison of the spatial landmark scatter of various 3D digitalization methods.

PubMed

Boldt, Florian; Weinzierl, Christian; Hertrich, Klaus; Hirschfelder, Ursula

2009-05-01

The aim of this study was to compare four different three-dimensional digitalization methods on the basis of the complex anatomical surface of a cleft lip and palate plaster cast, and to ascertain their accuracy when positioning 3D landmarks. A cleft lip and palate plaster cast was digitalized with the SCAN3D photo-optical scanner, the OPTIX 400S laser-optical scanner, the Somatom Sensation 64 computed tomography system and the MicroScribe MLX 3-axis articulated-arm digitizer. First, four examiners appraised by individual visual inspection the surface detail reproduction of the three non-tactile digitalization methods in comparison to the reference plaster cast. The four examiners then localized the landmarks five times at intervals of 2 weeks. This involved simply copying, or spatially tracing, the landmarks from a reference plaster cast to each model digitally reproduced by each digitalization method. Statistical analysis of the landmark distribution specific to each method was performed based on the 3D coordinates of the positioned landmarks. Visual evaluation of surface detail conformity assigned the photo-optical digitalization method an average score of 1.5, the highest subjectively-determined conformity (surpassing computer tomographic and laser-optical methods). The tactile scanning method revealed the lowest degree of 3D landmark scatter, 0.12 mm, and at 1.01 mm the lowest maximum 3D landmark scatter; this was followed by the computer tomographic, photo-optical and laser-optical methods (in that order). This study demonstrates that the landmarks' precision and reproducibility are determined by the complexity of the reference-model surface as well as the digital surface quality and individual ability of each evaluator to capture 3D spatial relationships. The differences in the 3D-landmark scatter values and lowest maximum 3D-landmark scatter between the best and the worst methods showed minor differences. The measurement results in this study reveal that it is not the method's precision but rather the complexity of the object analysis being planned that should determine which method is ultimately employed.

Pharmacophore Modelling and 4D-QSAR Study of Ruthenium(II) Arene Complexes as Anticancer Agents (Inhibitors) by Electron Conformational- Genetic Algorithm Method.

PubMed

Yavuz, Sevtap Caglar; Sabanci, Nazmiye; Saripinar, Emin

2018-01-01

The EC-GA method was employed in this study as a 4D-QSAR method, for the identification of the pharmacophore (Pha) of ruthenium(II) arene complex derivatives and quantitative prediction of activity. The arrangement of the computed geometric and electronic parameters for atoms and bonds of each compound occurring in a matrix is known as the electron-conformational matrix of congruity (ECMC). It contains the data from HF/3-21G level calculations. Compounds were represented by a group of conformers for each compound rather than a single conformation, known as fourth dimension to generate the model. ECMCs were compared within a certain range of tolerance values by using the EMRE program and the responsible pharmacophore group for ruthenium(II) arene complex derivatives was found. For selecting the sub-parameter which had the most effect on activity in the series and the calculation of theoretical activity values, the non-linear least square method and genetic algorithm which are included in the EMRE program were used. In addition, compounds were classified as the training and test set and the accuracy of the models was tested by cross-validation statistically. The model for training and test sets attained by the optimum 10 parameters gave highly satisfactory results with R2 training= 0.817, q 2=0.718 and SEtraining=0.066, q2 ext1 = 0.867, q2 ext2 = 0.849, q2 ext3 =0.895, ccctr = 0.895, ccctest = 0.930 and cccall = 0.905. Since there is no 4D-QSAR research on metal based organic complexes in the literature, this study is original and gives a powerful tool to the design of novel and selective ruthenium(II) arene complexes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Disruption of dopamine D1/D2 receptor complex is involved in the function of haloperidol in cardiac H9c2 cells.

PubMed

Lencesova, L; Szadvari, I; Babula, P; Kubickova, J; Chovancova, B; Lopusna, K; Rezuchova, I; Novakova, Z; Krizanova, O; Novakova, M

2017-12-15

Haloperidol is an antipsychotic agent and acts as dopamine D2 receptor (D2R) antagonist, as a prototypical ligand of sigma1 receptors (Sig1R) and it increases expression of type 1 IP 3 receptors (IP 3 R1). However, precise mechanism of haloperidol action on cardiomyocytes through dopaminergic signaling was not described yet. This study investigated a role of dopamine receptors in haloperidol-induced increase in IP 3 R1 and Sig1R, and compared physiological effect of melperone and haloperidol on basic heart parameters in rats. We used differentiated NG-108 cells and H9c2 cells. Gene expression, Western blot and immunofluorescence were used to evaluate haloperidol-induced differences; proximity ligation assay (PLA) and immunoprecipitation to determine interactions of D1/D2 receptors. To evaluate cardiac parameters, Wistar albino male rats were used. We have shown that antagonism of D2R with either haloperidol or melperone results in upregulation of both, IP 3 R1 and Sig1R, which is associated with increased D2R, but reduced D1R expression. Immunofluorescence, immunoprecipitation and PLA support formation of heteromeric D1/D2 complexes in H9c2 cells. Treatment with haloperidol (but not melperone) caused decrease in systolic and diastolic blood pressure and significant increase in heart rate. Because D1R/D2R complexes can engage Gq-like signaling in other experimental systems, these results are consistent with the possibility that disruption of D1R/D2R complex in H9c2 cells might cause a decrease in IP 3 R1 activity, which in turn may account for the increase expression of IP 3 R and Sig1R. D2R is probably not responsible for changes in cardiac parameters, since melperone did not have any effect. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Electrophysiological Rotor Ablation in In-Silico Modeling of Atrial Fibrillation: Comparisons with Dominant Frequency, Shannon Entropy, and Phase Singularity.

PubMed

Hwang, Minki; Song, Jun-Seop; Lee, Young-Seon; Li, Changyong; Shim, Eun Bo; Pak, Hui-Nam

2016-01-01

Although rotors have been considered among the drivers of atrial fibrillation (AF), the rotor definition is inconsistent. We evaluated the nature of rotors in 2D and 3D in- silico models of persistent AF (PeAF) by analyzing phase singularity (PS), dominant frequency (DF), Shannon entropy (ShEn), and complex fractionated atrial electrogram cycle length (CFAE-CL) and their ablation. Mother rotor was spatiotemporally defined as stationary reentries with a meandering tip remaining within half the wavelength and lasting longer than 5 s. We generated 2D- and 3D-maps of the PS, DF, ShEn, and CFAE-CL during AF. The spatial correlations and ablation outcomes targeting each parameter were analyzed. 1. In the 2D PeAF model, we observed a mother rotor that matched relatively well with DF (>9 Hz, 71.0%, p<0.001), ShEn (upper 2.5%, 33.2%, p<0.001), and CFAE-CL (lower 2.5%, 23.7%, p<0.001). 2. The 3D-PeAF model also showed mother rotors that had spatial correlations with DF (>5.5 Hz, 39.7%, p<0.001), ShEn (upper 8.5%, 15.1%, p <0.001), and CFAE (lower 8.5%, 8.0%, p = 0.002). 3. In both the 2D and 3D models, virtual ablation targeting the upper 5% of the DF terminated AF within 20 s, but not the ablations based on long-lasting PS, high ShEn area, or lower CFAE-CL area. Mother rotors were observed in both 2D and 3D human AF models. Rotor locations were well represented by DF, and their virtual ablation altered wave dynamics and terminated AF.

Electrophysiological Rotor Ablation in In-Silico Modeling of Atrial Fibrillation: Comparisons with Dominant Frequency, Shannon Entropy, and Phase Singularity

PubMed Central

Hwang, Minki; Song, Jun-Seop; Lee, Young-Seon; Li, Changyong; Shim, Eun Bo; Pak, Hui-Nam

2016-01-01

Background Although rotors have been considered among the drivers of atrial fibrillation (AF), the rotor definition is inconsistent. We evaluated the nature of rotors in 2D and 3D in- silico models of persistent AF (PeAF) by analyzing phase singularity (PS), dominant frequency (DF), Shannon entropy (ShEn), and complex fractionated atrial electrogram cycle length (CFAE-CL) and their ablation. Methods Mother rotor was spatiotemporally defined as stationary reentries with a meandering tip remaining within half the wavelength and lasting longer than 5 s. We generated 2D- and 3D-maps of the PS, DF, ShEn, and CFAE-CL during AF. The spatial correlations and ablation outcomes targeting each parameter were analyzed. Results 1. In the 2D PeAF model, we observed a mother rotor that matched relatively well with DF (>9 Hz, 71.0%, p<0.001), ShEn (upper 2.5%, 33.2%, p<0.001), and CFAE-CL (lower 2.5%, 23.7%, p<0.001). 2. The 3D-PeAF model also showed mother rotors that had spatial correlations with DF (>5.5 Hz, 39.7%, p<0.001), ShEn (upper 8.5%, 15.1%, p <0.001), and CFAE (lower 8.5%, 8.0%, p = 0.002). 3. In both the 2D and 3D models, virtual ablation targeting the upper 5% of the DF terminated AF within 20 s, but not the ablations based on long-lasting PS, high ShEn area, or lower CFAE-CL area. Conclusion Mother rotors were observed in both 2D and 3D human AF models. Rotor locations were well represented by DF, and their virtual ablation altered wave dynamics and terminated AF. PMID:26909492

The Effects of Extending of Co-planarity in a Series of Structurally Relative Polypyridyl Palladium(II) Complexes on DNA-binding and Cytotoxicity Properties

PubMed Central

Shahraki, Somaye; Mansouri-Torshizi, Hassan; Sori Nezami, Ziba; Ghahghaei, Arezou; Yaghoubi, Fatemeh; Divsalar, Adeleh; Saboury, Ali-Akbar; H. Shirazi, Farshad

2014-01-01

In depth interaction studies between calf thymus deoxyribonucleic acid (CT-DNA) and a series of four structurally relative palladium(II) complexes [Pd(en)(HB)](NO3)2 (a-d), where en is ethylenediamine and heterocyclic base (HB) is 2,2'-bipyridine (bpy, a); 1,10-phenanthroline (phen, b); dipyridoquinoxaline (dpq, c) and dipyridophenazine (dppz, d) (Figure 1), were performed. These studies have been investigated by utilizing the electronic absorption spectroscopy, fluorescence spectra and ethidium bromide (EBr) displacement and gel filtration techniques. a-d complexes cooperatively bind and denature the DNA at low concentrations. Their concentration at midpoint of transition, L1/2, follows the order a >> b > c > d. Also the g, the number of binding sites per 1000 nucleotides, follows the order a >> b ~ c > d. EBr and Scatchard experiments for a-d complexes suggest efficient intercalative binding affinity to CT-DNA giving the order: d > c > b > a. Several binding and thermodynamic parameters are also described. The biological activity of these cationic and water soluble palladium complexes were tested against chronic myelogenous leukemia cell line, K562. b, c and d complexes show cytotoxic concentration (Cc50) values much lower than cisplatin. PMID:25587317

Protein-ligand interaction energies with dispersion corrected density functional theory and high-level wave function based methods.

PubMed

Antony, Jens; Grimme, Stefan; Liakos, Dimitrios G; Neese, Frank

2011-10-20

With dispersion-corrected density functional theory (DFT-D3) intermolecular interaction energies for a diverse set of noncovalently bound protein-ligand complexes from the Protein Data Bank are calculated. The focus is on major contacts occurring between the drug molecule and the binding site. Generalized gradient approximation (GGA), meta-GGA, and hybrid functionals are used. DFT-D3 interaction energies are benchmarked against the best available wave function based results that are provided by the estimated complete basis set (CBS) limit of the local pair natural orbital coupled-electron pair approximation (LPNO-CEPA/1) and compared to MP2 and semiempirical data. The size of the complexes and their interaction energies (ΔE(PL)) varies between 50 and 300 atoms and from -1 to -65 kcal/mol, respectively. Basis set effects are considered by applying extended sets of triple- to quadruple-ζ quality. Computed total ΔE(PL) values show a good correlation with the dispersion contribution despite the fact that the protein-ligand complexes contain many hydrogen bonds. It is concluded that an adequate, for example, asymptotically correct, treatment of dispersion interactions is necessary for the realistic modeling of protein-ligand binding. Inclusion of the dispersion correction drastically reduces the dependence of the computed interaction energies on the density functional compared to uncorrected DFT results. DFT-D3 methods provide results that are consistent with LPNO-CEPA/1 and MP2, the differences of about 1-2 kcal/mol on average (<5% of ΔE(PL)) being on the order of their accuracy, while dispersion-corrected semiempirical AM1 and PM3 approaches show a deviating behavior. The DFT-D3 results are found to depend insignificantly on the choice of the short-range damping model. We propose to use DFT-D3 as an essential ingredient in a QM/MM approach for advanced virtual screening approaches of protein-ligand interactions to be combined with similarly "first-principle" accounts for the estimation of solvation and entropic effects.

Spectrally formulated user-defined element in Abaqus for wave motion analysis and health monitoring of composite structures

NASA Astrophysics Data System (ADS)

Khalili, Ashkan

Wave propagation analysis in 1-D and 2-D composite structures is performed efficiently and accurately through the formulation of a User-Defined Element (UEL) based on the wavelet spectral finite element (WSFE) method. The WSFE method is based on the first order shear deformation theory which yields accurate results for wave motion at high frequencies. The wave equations are reduced to ordinary differential equations using Daubechies compactly supported, orthonormal, wavelet scaling functions for approximations in time and one spatial dimension. The 1-D and 2-D WSFE models are highly efficient computationally and provide a direct relationship between system input and output in the frequency domain. The UEL is formulated and implemented in Abaqus for wave propagation analysis in composite structures with complexities. Frequency domain formulation of WSFE leads to complex valued parameters, which are decoupled into real and imaginary parts and presented to Abaqus as real values. The final solution is obtained by forming a complex value using the real number solutions given by Abaqus. Several numerical examples are presented here for 1-D and 2-D composite waveguides. Wave motions predicted by the developed UEL correlate very well with Abaqus simulations using shear flexible elements. The results also show that the UEL largely retains computational efficiency of the WSFE method and extends its ability to model complex features. An enhanced cross-correlation method (ECCM) is developed in order to accurately predict damage location in plates. Three major modifications are proposed to the widely used cross-correlation method (CCM) to improve damage localization capabilities, namely actuator-sensor configuration, signal pre-processing method, and signal post-processing method. The ECCM is investigated numerically (FEM simulation) and experimentally. Experimental investigations for damage detection employ a PZT transducer as actuator and laser Doppler vibrometer as sensor. Both numerical and experimental results show that the developed method is capable of damage localization with high precision. Further, ECCM is used to detect and localize debonding in a composite material skin-stiffener joint. The UEL is used to represent the healthy case whereas the damaged case is simulated using Abaqus. It is shown that the ECCM successfully detects the location of the debond in the skin-stiffener joint.

Modeling of flow-induced shear stress applied on 3D cellular scaffolds: Implications for vascular tissue engineering.

PubMed

Lesman, Ayelet; Blinder, Yaron; Levenberg, Shulamit

2010-02-15

Novel tissue-culture bioreactors employ flow-induced shear stress as a means of mechanical stimulation of cells. We developed a computational fluid dynamics model of the complex three-dimensional (3D) microstructure of a porous scaffold incubated in a direct perfusion bioreactor. Our model was designed to predict high shear-stress values within the physiological range of those naturally sensed by vascular cells (1-10 dyne/cm(2)), and will thereby provide suitable conditions for vascular tissue-engineering experiments. The model also accounts for cellular growth, which was designed as an added cell layer grown on all scaffold walls. Five model variants were designed, with geometric differences corresponding to cell-layer thicknesses of 0, 50, 75, 100, and 125 microm. Four inlet velocities (0.5, 1, 1.5, and 2 cm/s) were applied to each model. Wall shear-stress distribution and overall pressure drop calculations were then used to characterize the relation between flow rate, shear stress, cell-layer thickness, and pressure drop. The simulations showed that cellular growth within 3D scaffolds exposes cells to elevated shear stress, with considerably increasing average values in correlation to cell growth and inflow velocity. Our results provide in-depth analysis of the microdynamic environment of cells cultured within 3D environments, and thus provide advanced control over tissue development in vitro. 2009 Wiley Periodicals, Inc.

A Weak Constraint 4D-Var Assimilation System for the Navy Coastal Model Using the Representer Method

DTIC Science & Technology

2013-01-01

the help of the Parametric Fortrai compiler (PFC), Erwig et al. 2007 . Some general circulation models of the complexity of NCOM have seen 1 similar...the Mir general circulation model (MITgcm, Marotzke et al. 1999) also used in the ECCO consortium assimilation experiments ( Stammer et al. 2002...using the« inverse Regional Ocean Modeling System (IROMS, Di Lorenzo et al. 2007 ) with horizontal resolutions of 10 and 30km. The CCS is a large

Microfluidic 3D models of cancer

PubMed Central

Sung, Kyung Eun; Beebe, David J.

2014-01-01

Despite advances in medicine and biomedical sciences, cancer still remains a major health issue. Complex interactions between tumors and their microenvironment contribute to tumor initiation and progression and also contribute to the development of drug resistant tumor cell populations. The complexity and heterogeneity of tumors and their microenvironment make it challenging to both study and treat cancer. Traditional animal cancer models and in vitro cancer models are limited in their ability to recapitulate human structures and functions, thus hindering the identification of appropriate drug targets and therapeutic strategies. The development and application of microfluidic 3D cancer models has the potential to overcome some of the limitations inherent to traditional models. This review summarizes the progress in microfluidic 3D cancer models, their benefits, and their broad application to basic cancer biology, drug screening, and drug discovery. PMID:25017040

A Generalized QMRA Beta-Poisson Dose-Response Model.

PubMed

Xie, Gang; Roiko, Anne; Stratton, Helen; Lemckert, Charles; Dunn, Peter K; Mengersen, Kerrie

2016-10-01

Quantitative microbial risk assessment (QMRA) is widely accepted for characterizing the microbial risks associated with food, water, and wastewater. Single-hit dose-response models are the most commonly used dose-response models in QMRA. Denoting PI(d) as the probability of infection at a given mean dose d, a three-parameter generalized QMRA beta-Poisson dose-response model, PI(d|α,β,r*), is proposed in which the minimum number of organisms required for causing infection, K min , is not fixed, but a random variable following a geometric distribution with parameter 0

Water molecules in the antibody-antigen interface of the structure of the Fab HyHEL-5-lysozyme complex at 1.7 A resolution: comparison with results from isothermal titration calorimetry.

PubMed

Cohen, Gerson H; Silverton, Enid W; Padlan, Eduardo A; Dyda, Fred; Wibbenmeyer, Jamie A; Willson, Richard C; Davies, David R

2005-05-01

The structure of the complex between hen egg-white lysozyme and the Fab HyHEL-5 at 2.7 A resolution has previously been reported [Cohen et al. (1996), Acta Cryst. D52, 315-326]. With the availability of recombinant Fab, the X-ray structure of the complex has been re-evaluated at 1.7 A resolution. The refined structure has yielded a detailed picture of the Fab-lysozyme interface, showing the high complementarity of the protein surfaces as well as several water molecules within the interface that complete the good fit. The model of the full complex has improved significantly, yielding an R(work) of 19.5%. With this model, the structural results can be compared with the results of isothermal titration calorimetry. An attempt has been made to estimate the changes in bound waters that accompany complex formation and the difficulties inherent in using the crystal structures to provide the information necessary to make this calculation are discussed.

Accelerated Gaussian mixture model and its application on image segmentation

NASA Astrophysics Data System (ADS)

Zhao, Jianhui; Zhang, Yuanyuan; Ding, Yihua; Long, Chengjiang; Yuan, Zhiyong; Zhang, Dengyi

2013-03-01

Gaussian mixture model (GMM) has been widely used for image segmentation in recent years due to its superior adaptability and simplicity of implementation. However, traditional GMM has the disadvantage of high computational complexity. In this paper an accelerated GMM is designed, for which the following approaches are adopted: establish the lookup table for Gaussian probability matrix to avoid the repetitive probability calculations on all pixels, employ the blocking detection method on each block of pixels to further decrease the complexity, change the structure of lookup table from 3D to 1D with more simple data type to reduce the space requirement. The accelerated GMM is applied on image segmentation with the help of OTSU method to decide the threshold value automatically. Our algorithm has been tested through image segmenting of flames and faces from a set of real pictures, and the experimental results prove its efficiency in segmentation precision and computational cost.

Identification of a protein–protein interaction between KCNE1 and the activation gate machinery of KCNQ1

PubMed Central

Lvov, Anatoli; Gage, Steven D.; Berrios, Virla M.

2010-01-01

KCNQ1 channels assemble with KCNE1 transmembrane (TM) peptides to form voltage-gated K+ channel complexes with slow activation gate opening. The cytoplasmic C-terminal domain that abuts the KCNE1 TM segment has been implicated in regulating KCNQ1 gating, yet its interaction with KCNQ1 has not been described. Here, we identified a protein–protein interaction between the KCNE1 C-terminal domain and the KCNQ1 S6 activation gate and S4–S5 linker. Using cysteine cross-linking, we biochemically screened over 300 cysteine pairs in the KCNQ1–KCNE1 complex and identified three residues in KCNQ1 (H363C, P369C, and I257C) that formed disulfide bonds with cysteine residues in the KCNE1 C-terminal domain. Statistical analysis of cross-link efficiency showed that H363C preferentially reacted with KCNE1 residues H73C, S74C, and D76C, whereas P369C showed preference for only D76C. Electrophysiological investigation of the mutant K+ channel complexes revealed that the KCNQ1 residue, H363C, formed cross-links not only with KCNE1 subunits, but also with neighboring KCNQ1 subunits in the complex. Cross-link formation involving the H363C residue was state dependent, primarily occurring when the KCNQ1–KCNE1 complex was closed. Based on these biochemical and electrophysiological data, we generated a closed-state model of the KCNQ1–KCNE1 cytoplasmic region where these protein–protein interactions are poised to slow activation gate opening. PMID:20479109

The Skilled Counselor Training Model: Skills Acquisition, Self-Assessment, and Cognitive Complexity

ERIC Educational Resources Information Center

Little, Cassandra; Packman, Jill; Smaby, Marlowe H.; Maddux, Cleborne D.

2005-01-01

The authors evaluated the effectiveness of the Skilled Counselor Training Model (SCTM; M. H. Smaby, C. D. Maddux, E. Torres-Rivera, & R. Zimmick, 1999) in teaching counseling skills and in fostering counselor cognitive complexity. Counselor trainees who completed the SCTM had better counseling skills and higher levels of cognitive complexity than…

A quantitative evaluation of the three dimensional reconstruction of patients' coronary arteries.

PubMed

Klein, J L; Hoff, J G; Peifer, J W; Folks, R; Cooke, C D; King, S B; Garcia, E V

1998-04-01

Through extensive training and experience angiographers learn to mentally reconstruct the three dimensional (3D) relationships of the coronary arterial branches. Graphic computer technology can assist angiographers to more quickly visualize the coronary 3D structure from limited initial views and then help to determine additional helpful views by predicting subsequent angiograms before they are obtained. A new computer method for facilitating 3D reconstruction and visualization of human coronary arteries was evaluated by reconstructing biplane left coronary angiograms from 30 patients. The accuracy of the reconstruction was assessed in two ways: 1) by comparing the vessel's centerlines of the actual angiograms with the centerlines of a 2D projection of the 3D model projected into the exact angle of the actual angiogram; and 2) by comparing two 3D models generated by different simultaneous pairs on angiograms. The inter- and intraobserver variability of reconstruction were evaluated by mathematically comparing the 3D model centerlines of repeated reconstructions. The average absolute corrected displacement of 14,662 vessel centerline points in 2D from 30 patients was 1.64 +/- 2.26 mm. The average corrected absolute displacement of 3D models generated from different biplane pairs was 7.08 +/- 3.21 mm. The intraobserver variability of absolute 3D corrected displacement was 5.22 +/- 3.39 mm. The interobserver variability was 6.6 +/- 3.1 mm. The centerline analyses show that the reconstruction algorithm is mathematically accurate and reproducible. The figures presented in this report put these measurement errors into clinical perspective showing that they yield an accurate representation of the clinically relevant information seen on the actual angiograms. These data show that this technique can be clinically useful by accurately displaying in three dimensions the complex relationships of the branches of the coronary arterial tree.

Optimal management of reconfigurable manufacturing system modeling with Petri nets developed three-dimensional - RPD3D

NASA Astrophysics Data System (ADS)

Teodor, F.; Marinescu, V.; Epureanu, A.

2016-11-01

Modeling of reconfigurable manufacturing systems would have done using existing Petri net types, but the complexity and dynamics of the new manufacturing system, mainly data reconfiguration feature, required looking for a more compact representation with many variables that to model as accurately not only the normal operation of the production system but can capture and model and reconfiguration process. Thus, it was necessary to create a new class of Petri nets, called RPD3D (Developed Petri nets with three dimensional) showing the name of both lineage (new class derived from Petri nets developed, created in 2000 by Prof. Dr. Ing Vasile Marinescu in his doctoral thesis) [1], but the most important of the new features defining (transformation from one 2D model into a 3D model).The idea was to introduce the classical model of a Petri third dimension to be able to overlay multiple levels (layers) formed in 2D or 3D Petri nets that interact with each other (receiving or giving commands to enable or disable the various modules together simulating the operation of reconfigurable manufacturing systems). The aim is to present a new type of Petri nets called RPD3D - Developed Petri three-dimensional model used for optimal control and simulation of reconfigurable manufacturing systems manufacture of products such systems.

A Review of Discrete Element Method (DEM) Particle Shapes and Size Distributions for Lunar Soil

NASA Technical Reports Server (NTRS)

Lane, John E.; Metzger, Philip T.; Wilkinson, R. Allen

2010-01-01

As part of ongoing efforts to develop models of lunar soil mechanics, this report reviews two topics that are important to discrete element method (DEM) modeling the behavior of soils (such as lunar soils): (1) methods of modeling particle shapes and (2) analytical representations of particle size distribution. The choice of particle shape complexity is driven primarily by opposing tradeoffs with total number of particles, computer memory, and total simulation computer processing time. The choice is also dependent on available DEM software capabilities. For example, PFC2D/PFC3D and EDEM support clustering of spheres; MIMES incorporates superquadric particle shapes; and BLOKS3D provides polyhedra shapes. Most commercial and custom DEM software supports some type of complex particle shape beyond the standard sphere. Convex polyhedra, clusters of spheres and single parametric particle shapes such as the ellipsoid, polyellipsoid, and superquadric, are all motivated by the desire to introduce asymmetry into the particle shape, as well as edges and corners, in order to better simulate actual granular particle shapes and behavior. An empirical particle size distribution (PSD) formula is shown to fit desert sand data from Bagnold. Particle size data of JSC-1a obtained from a fine particle analyzer at the NASA Kennedy Space Center is also fitted to a similar empirical PSD function.

IGLOO: an Intermediate Complexity Framework to Simulate Greenland Ice-Ocean Interactions

NASA Astrophysics Data System (ADS)

Perrette, M.; Calov, R.; Beckmann, J.; Alexander, D.; Beyer, S.; Ganopolski, A.

2017-12-01

The Greenland ice-sheet is a major contributor to current and future sea level rise associated to climate warming. It is widely believed that over a century time scale, surface melting is the main driver of Greenland ice volume change, in contrast to melting by the ocean. It is due to relatively warmer air and less ice area exposed to melting by ocean water compared to Antarctica, its southern, larger twin. Yet most modeling studies do not have adequate grid resolution to represent fine-scale outlet glaciers and fjords at the margin of the ice sheet, where ice-ocean interaction occurs, and must use rather crude parameterizations to represent this process. Additionally, the ice-sheet area grounded below sea level has been reassessed upwards in the most recent estimates of bedrock elevation under the Greenland ice sheet, revealing a larger potential for marine-mediated melting than previously thought. In this work, we develop an original approach to estimate potential Greenland ice sheet contribution to sea level rise from ocean melting, in an intermediate complexity framework, IGLOO. We use a medium-resolution (5km) ice-sheet model coupled interactively to a number of 1-D flowline models for the individual outlet glaciers. We propose a semi-objective methodology to derive 1-D glacier geometries from 2-D Greenland datasets, as well as preliminary results of coupled ice-sheet-glaciers simulations with IGLOO.

Square-antiprismatic eight-coordinate complexes of divalent first-row transition metal cations: a density functional theory exploration of the electronic-structural landscape.

PubMed

Conradie, Jeanet; Patra, Ashis K; Harrop, Todd C; Ghosh, Abhik

2015-02-16

Density functional theory (in the form of the PW91, BP86, OLYP, and B3LYP exchange-correlation functionals) has been used to map out the low-energy states of a series of eight-coordinate square-antiprismatic (D2d) first-row transition metal complexes, involving Mn(II), Fe(II), Co(II), Ni(II), and Cu(II), along with a pair of tetradentate N4 ligands. Of the five complexes, the Mn(II) and Fe(II) complexes have been synthesized and characterized structurally and spectroscopically, whereas the other three are as yet unknown. Each N4 ligand consists of a pair of terminal imidazole units linked by an o-phenylenediimine unit. The imidazole units are the strongest ligands in these complexes and dictate the spatial disposition of the metal three-dimensional orbitals. Thus, the dx(2)-y(2) orbital, whose lobes point directly at the coordinating imidazole nitrogens, has the highest orbital energy among the five d orbitals, whereas the dxy orbital has the lowest orbital energy. In general, the following orbital ordering (in order of increasing orbital energy) was found to be operative: dxy < dxz = dyz ≤ dz(2) < dx(2)-y(2). The square-antiprism geometry does not lead to large energy gaps between the d orbitals, which leads to an S = 2 ground state for the Fe(II) complex. Nevertheless, the dxy orbital has significantly lower energy relative to that of the dxz and dyz orbitals. Accordingly, the ground state of the Fe(II) complex corresponds unambiguously to a dxy(2)dxz(1)dyz(1)dz(2)(1)dx(2)-y(2)(1) electronic configuration. Unsurprisingly, the Mn(II) complex has an S = 5/2 ground state and no low-energy d-d excited states within 1.0 eV of the ground state. The Co(II) complex, on the other hand, has both a low-lying S = 1/2 state and multiple low-energy S = 3/2 states. Very long metal-nitrogen bonds are predicted for the Ni(II) and Cu(II) complexes; these bonds may be too fragile to survive in solution or in the solid state, and the complexes may therefore not be isolable. Overall, the different exchange-correlation functionals provided a qualitatively consistent and plausible picture of the low-energy d-d excited states of the complexes.

Advanced Cell Culture Techniques for Cancer Drug Discovery

PubMed Central

Lovitt, Carrie J.; Shelper, Todd B.; Avery, Vicky M.

2014-01-01

Human cancer cell lines are an integral part of drug discovery practices. However, modeling the complexity of cancer utilizing these cell lines on standard plastic substrata, does not accurately represent the tumor microenvironment. Research into developing advanced tumor cell culture models in a three-dimensional (3D) architecture that more prescisely characterizes the disease state have been undertaken by a number of laboratories around the world. These 3D cell culture models are particularly beneficial for investigating mechanistic processes and drug resistance in tumor cells. In addition, a range of molecular mechanisms deconstructed by studying cancer cells in 3D models suggest that tumor cells cultured in two-dimensional monolayer conditions do not respond to cancer therapeutics/compounds in a similar manner. Recent studies have demonstrated the potential of utilizing 3D cell culture models in drug discovery programs; however, it is evident that further research is required for the development of more complex models that incorporate the majority of the cellular and physical properties of a tumor. PMID:24887773

Advanced cell culture techniques for cancer drug discovery.

PubMed

Lovitt, Carrie J; Shelper, Todd B; Avery, Vicky M

2014-05-30

Human cancer cell lines are an integral part of drug discovery practices. However, modeling the complexity of cancer utilizing these cell lines on standard plastic substrata, does not accurately represent the tumor microenvironment. Research into developing advanced tumor cell culture models in a three-dimensional (3D) architecture that more prescisely characterizes the disease state have been undertaken by a number of laboratories around the world. These 3D cell culture models are particularly beneficial for investigating mechanistic processes and drug resistance in tumor cells. In addition, a range of molecular mechanisms deconstructed by studying cancer cells in 3D models suggest that tumor cells cultured in two-dimensional monolayer conditions do not respond to cancer therapeutics/compounds in a similar manner. Recent studies have demonstrated the potential of utilizing 3D cell culture models in drug discovery programs; however, it is evident that further research is required for the development of more complex models that incorporate the majority of the cellular and physical properties of a tumor.

A quantitative systems pharmacology model of blood coagulation network describes in vivo biomarker changes in non-bleeding subjects.

PubMed

Lee, D; Nayak, S; Martin, S W; Heatherington, A C; Vicini, P; Hua, F

2016-12-01

Essentials Baseline coagulation activity can be detected in non-bleeding state by in vivo biomarker levels. A detailed mathematical model of coagulation was developed to describe the non-bleeding state. Optimized model described in vivo biomarkers with recombinant activated factor VII treatment. Sensitivity analysis predicted prothrombin fragment 1 + 2 and D-dimer are regulated differently. Background Prothrombin fragment 1 + 2 (F 1 + 2 ), thrombin-antithrombin III complex (TAT) and D-dimer can be detected in plasma from non-bleeding hemostatically normal subjects or hemophilic patients. They are often used as safety or pharmacodynamic biomarkers for hemostatis-modulating therapies in the clinic, and provide insights into in vivo coagulation activity. Objectives To develop a quantitative systems pharmacology (QSP) model of the blood coagulation network to describe in vivo biomarkers, including F 1 + 2 , TAT, and D-dimer, under non-bleeding conditions. Methods The QSP model included intrinsic and extrinsic coagulation pathways, platelet activation state-dependent kinetics, and a two-compartment pharmacokinetics model for recombinant activated factor VII (rFVIIa). Literature data on F 1 + 2 and D-dimer at baseline and changes with rFVIIa treatment were used for parameter optimization. Multiparametric sensitivity analysis (MPSA) was used to understand key proteins that regulate F 1 + 2 , TAT and D-dimer levels. Results The model was able to describe tissue factor (TF)-dependent baseline levels of F 1 + 2 , TAT and D-dimer in a non-bleeding state, and their increases in hemostatically normal subjects and hemophilic patients treated with different doses of rFVIIa. The amount of TF required is predicted to be very low in a non-bleeding state. The model also predicts that these biomarker levels will be similar in hemostatically normal subjects and hemophilic patients. MPSA revealed that F 1 + 2 and TAT levels are highly correlated, and that D-dimer is more sensitive to the perturbation of coagulation protein concentrations. Conclusions A QSP model for non-bleeding baseline coagulation activity was established with data from clinically relevant in vivo biomarkers at baseline and changes in response to rFVIIa treatment. This model will provide future mechanistic insights into this system. © 2016 International Society on Thrombosis and Haemostasis.

Comparison of molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) and molecular mechanics-three-dimensional reference interaction site model (MM-3D-RISM) method to calculate the binding free energy of protein-ligand complexes: Effect of metal ion and advance statistical test

NASA Astrophysics Data System (ADS)

Pandey, Preeti; Srivastava, Rakesh; Bandyopadhyay, Pradipta

2018-03-01

The relative performance of MM-PBSA and MM-3D-RISM methods to estimate the binding free energy of protein-ligand complexes is investigated by applying these to three proteins (Dihydrofolate Reductase, Catechol-O-methyltransferase, and Stromelysin-1) differing in the number of metal ions they contain. None of the computational methods could distinguish all the ligands based on their calculated binding free energies (as compared to experimental values). The difference between the two comes from both polar and non-polar part of solvation. For charged ligand case, MM-PBSA and MM-3D-RISM give a qualitatively different result for the polar part of solvation.

Molecular architecture of the yeast Mediator complex

PubMed Central

Robinson, Philip J; Trnka, Michael J; Pellarin, Riccardo; Greenberg, Charles H; Bushnell, David A; Davis, Ralph; Burlingame, Alma L; Sali, Andrej; Kornberg, Roger D

2015-01-01

The 21-subunit Mediator complex transduces regulatory information from enhancers to promoters, and performs an essential role in the initiation of transcription in all eukaryotes. Structural information on two-thirds of the complex has been limited to coarse subunit mapping onto 2-D images from electron micrographs. We have performed chemical cross-linking and mass spectrometry, and combined the results with information from X-ray crystallography, homology modeling, and cryo-electron microscopy by an integrative modeling approach to determine a 3-D model of the entire Mediator complex. The approach is validated by the use of X-ray crystal structures as internal controls and by consistency with previous results from electron microscopy and yeast two-hybrid screens. The model shows the locations and orientations of all Mediator subunits, as well as subunit interfaces and some secondary structural elements. Segments of 20–40 amino acid residues are placed with an average precision of 20 Å. The model reveals roles of individual subunits in the organization of the complex. DOI: http://dx.doi.org/10.7554/eLife.08719.001 PMID:26402457

Synthesis, characterization and anti-microbial evaluation of Cu(II), Ni(II), Pt(II) and Pd(II) sulfonylhydrazone complexes; 2D-QSAR analysis of Ni(II) complexes of sulfonylhydrazone derivatives

NASA Astrophysics Data System (ADS)

Özbek, Neslihan; Alyar, Saliha; Alyar, Hamit; Şahin, Ertan; Karacan, Nurcan

2013-05-01

Copper(II), nickel(II), platinum(II) and palladium(II) complexes with 2-hydroxy-1-naphthaldehyde-N-methylpropanesulfonylhydrazone (nafpsmh) derived from propanesulfonic acid-1-methylhydrazide (psmh) were synthesized, their structure were identified, and antimicrobial activity of the compounds was screened against three Gram-positive and three Gram-negative bacteria. The results of antimicrobial studies indicate that Pt(II) and Pd(II) complexes showed the most activity against all bacteria. The crystal structure of 2-hydroxy-1-naphthaldehyde-N-methylpropanesulfonylhydrazone (nafpsmh) was also investigated by X-ray analysis. A series of Ni(II) sulfonyl hydrazone complexes (1-33) was synthesized and tested in vitro against Escherichia coli and Staphylococcus aureus. Their antimicrobial activities were used in the QSAR analysis. Four-parameter QSAR models revealed that nucleophilic reaction index for Ni and O atoms, and HOMO-LUMO energy gap play key roles in the antimicrobial activity.

The utility of 3D printing for surgical planning and patient-specific implant design for complex spinal pathologies: case report.

PubMed

Mobbs, Ralph J; Coughlan, Marc; Thompson, Robert; Sutterlin, Chester E; Phan, Kevin

2017-04-01

OBJECTIVE There has been a recent renewed interest in the use and potential applications of 3D printing in the assistance of surgical planning and the development of personalized prostheses. There have been few reports on the use of 3D printing for implants designed to be used in complex spinal surgery. METHODS The authors report 2 cases in which 3D printing was used for surgical planning as a preoperative mold, and for a custom-designed titanium prosthesis: one patient with a C-1/C-2 chordoma who underwent tumor resection and vertebral reconstruction, and another patient with a custom-designed titanium anterior fusion cage for an unusual congenital spinal deformity. RESULTS In both presented cases, the custom-designed and custom-built implants were easily slotted into position, which facilitated the surgery and shortened the procedure time, avoiding further complex reconstruction such as harvesting rib or fibular grafts and fashioning these grafts intraoperatively to fit the defect. Radiological follow-up for both cases demonstrated successful fusion at 9 and 12 months, respectively. CONCLUSIONS These cases demonstrate the feasibility of the use of 3D modeling and printing to develop personalized prostheses and can ease the difficulty of complex spinal surgery. Possible future directions of research include the combination of 3D-printed implants and biologics, as well as the development of bioceramic composites and custom implants for load-bearing purposes.

Mental visualization of objects from cross-sectional images

PubMed Central

Wu, Bing; Klatzky, Roberta L.; Stetten, George D.

2011-01-01

We extended the classic anorthoscopic viewing procedure to test a model of visualization of 3D structures from 2D cross-sections. Four experiments were conducted to examine key processes described in the model, localizing cross-sections within a common frame of reference and spatiotemporal integration of cross sections into a hierarchical object representation. Participants used a hand-held device to reveal a hidden object as a sequence of cross-sectional images. The process of localization was manipulated by contrasting two displays, in-situ vs. ex-situ, which differed in whether cross sections were presented at their source locations or displaced to a remote screen. The process of integration was manipulated by varying the structural complexity of target objects and their components. Experiments 1 and 2 demonstrated visualization of 2D and 3D line-segment objects and verified predictions about display and complexity effects. In Experiments 3 and 4, the visualized forms were familiar letters and numbers. Errors and orientation effects showed that displacing cross-sectional images to a remote display (ex-situ viewing) impeded the ability to determine spatial relationships among pattern components, a failure of integration at the object level. PMID:22217386

Design and Validation of 3D Printed Complex Bone Models with Internal Anatomic Fidelity for Surgical Training and Rehearsal.

PubMed

Unger, Bertram J; Kraut, Jay; Rhodes, Charlotte; Hochman, Jordan

2014-01-01

Physical models of complex bony structures can be used for surgical skills training. Current models focus on surface rendering but suffer from a lack of internal accuracy due to limitations in the manufacturing process. We describe a technique for generating internally accurate rapid-prototyped anatomical models with solid and hollow structures from clinical and microCT data using a 3D printer. In a face validation experiment, otolaryngology residents drilled a cadaveric bone and its corresponding printed model. The printed bone models were deemed highly realistic representations across all measured parameters and the educational value of the models was strongly appreciated.

A set of alkali and alkaline-earth coordination polymers based on the ligand 2-(1H-benzotriazol-1-yl) acetic acid: Effects the radius of metal ions on structures and properties

NASA Astrophysics Data System (ADS)

Wang, Jin-Hua; Tang, Gui-Mei; Qin, Ting-Xiao; Yan, Shi-Chen; Wang, Yong-Tao; Cui, Yue-Zhi; Weng Ng, Seik

2014-11-01

Four new metal coordination complexes, namely, [Na(BTA)]n (1), [K2(BTA)2(μ2-H2O)]n (2), and [M(BTA)2(H2O)2]n (M=Ca(II) and Sr(II) for 3 and 4, respectively) [BTA=2-(1H-benzotriazol-1-yl) acetic anion], have been obtained under hydrothermal condition, by reacting the different alkali and alkaline-earth metal hydroxides with HBTA. Complexes 1-4 were structurally characterized by X-ray single-crystal diffraction, EA, IR, PXRD, and thermogravimetry analysis (TGA). These complexes display low-dimensional features displaying various two-dimensional (2D) and one-dimensional (1D) coordination motifs. Complex 1 displays a 2D layer with the thickness of 1.5 nm and possesses a topologic structure of a 11 nodal net with Schläfli symbol of {318}. Complex 2 also shows a thick 2D sheet and its topologic structure is a 9 nodes with Schläfli symbol of {311×42}. Complexes 3 and 4 possess a 1D linear chain and further stack via hydrogen bonding interactions to generate a three-dimensional supramolecular architecture. These results suggest that both the coordination preferences of the metal ions and the versatile nature of this flexible ligand play a critical role in the final structures. The luminescent spectra show strong emission intensities in complexes 1-4, which display violet photoluminescence. Additionally, ferroelectric, dielectric and nonlinear optic (NLO) second-harmonic generation (SHG) properties of 2 are discussed in detail.

3D printing based on cardiac CT assists anatomic visualization prior to transcatheter aortic valve replacement.

PubMed

Ripley, Beth; Kelil, Tatiana; Cheezum, Michael K; Goncalves, Alexandra; Di Carli, Marcelo F; Rybicki, Frank J; Steigner, Mike; Mitsouras, Dimitrios; Blankstein, Ron

2016-01-01

3D printing is a promising technique that may have applications in medicine, and there is expanding interest in the use of patient-specific 3D models to guide surgical interventions. To determine the feasibility of using cardiac CT to print individual models of the aortic root complex for transcatheter aortic valve replacement (TAVR) planning as well as to determine the ability to predict paravalvular aortic regurgitation (PAR). This retrospective study included 16 patients (9 with PAR identified on blinded interpretation of post-procedure trans-thoracic echocardiography and 7 age, sex, and valve size-matched controls with no PAR). 3D printed models of the aortic root were created from pre-TAVR cardiac computed tomography data. These models were fitted with printed valves and predictions regarding post-implant PAR were made using a light transmission test. Aortic root 3D models were highly accurate, with excellent agreement between annulus measurements made on 3D models and those made on corresponding 2D data (mean difference of -0.34 mm, 95% limits of agreement: ± 1.3 mm). The 3D printed valve models were within 0.1 mm of their designed dimensions. Examination of the fit of valves within patient-specific aortic root models correctly predicted PAR in 6 of 9 patients (6 true positive, 3 false negative) and absence of PAR in 5 of 7 patients (5 true negative, 2 false positive). Pre-TAVR 3D-printing based on cardiac CT provides a unique patient-specific method to assess the physical interplay of the aortic root and implanted valves. With additional optimization, 3D models may complement traditional techniques used for predicting which patients are more likely to develop PAR. Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Evaluation and development of satellite inferences of convective storm intensity using combined case study analysis and thunderstorm model simulations

NASA Technical Reports Server (NTRS)

Cotton, W. R.; Tripoli, G. J.

1980-01-01

Major research accomplishments which were achieved during the first year of the grant are summarized. The research concentrated in the following areas: (1) an examination of observational requirements for predicting convective storm development and intensity as suggested by recent numerical experiments; (2) interpretation of recent 3D numerical experiments with regard to the relationship between overshooting tops and surface wind gusts; (3) the development of software for emulating satellite-inferred cloud properties using 3D cloud model predicted data; and (4) the development of a conceptual/semi-quantitative model of eastward propagating, mesoscale convective complexes forming to the lee of the Rocky Mountains.

Comparison of new generation low-complexity flood inundation mapping tools with a hydrodynamic model

NASA Astrophysics Data System (ADS)

Afshari, Shahab; Tavakoly, Ahmad A.; Rajib, Mohammad Adnan; Zheng, Xing; Follum, Michael L.; Omranian, Ehsan; Fekete, Balázs M.

2018-01-01

The objective of this study is to compare two new generation low-complexity tools, AutoRoute and Height Above the Nearest Drainage (HAND), with a two-dimensional hydrodynamic model (Hydrologic Engineering Center-River Analysis System, HEC-RAS 2D). The assessment was conducted on two hydrologically different and geographically distant test-cases in the United States, including the 16,900 km2 Cedar River (CR) watershed in Iowa and a 62 km2 domain along the Black Warrior River (BWR) in Alabama. For BWR, twelve different configurations were set up for each of the models, including four different terrain setups (e.g. with and without channel bathymetry and a levee), and three flooding conditions representing moderate to extreme hazards at 10-, 100-, and 500-year return periods. For the CR watershed, models were compared with a simplistic terrain setup (without bathymetry and any form of hydraulic controls) and one flooding condition (100-year return period). Input streamflow forcing data representing these hypothetical events were constructed by applying a new fusion approach on National Water Model outputs. Simulated inundation extent and depth from AutoRoute, HAND, and HEC-RAS 2D were compared with one another and with the corresponding FEMA reference estimates. Irrespective of the configurations, the low-complexity models were able to produce inundation extents similar to HEC-RAS 2D, with AutoRoute showing slightly higher accuracy than the HAND model. Among four terrain setups, the one including both levee and channel bathymetry showed lowest fitness score on the spatial agreement of inundation extent, due to the weak physical representation of low-complexity models compared to a hydrodynamic model. For inundation depth, the low-complexity models showed an overestimating tendency, especially in the deeper segments of the channel. Based on such reasonably good prediction skills, low-complexity flood models can be considered as a suitable alternative for fast predictions in large-scale hyper-resolution operational frameworks, without completely overriding hydrodynamic models' efficacy.

Structural modeling of glucanase-substrate complexes suggests a conserved tyrosine is involved in carbohydrate recognition in plant 1,3-1,4-β- d-glucanases

NASA Astrophysics Data System (ADS)

Tsai, Li-Chu; Chen, Yi-Ning; Shyur, Lie-Fen

2008-12-01

Glycosyl hydrolase family 16 (GHF16) truncated Fibrobacter succinogenes (TFs) and GHF17 barley 1,3-1,4-β- d-glucanases (β-glucanases) possess different structural folds, β-jellyroll and (β/α)8, although they both catalyze the specific hydrolysis of β-1,4 glycosidic bonds adjacent to β-1,3 linkages in mixed β-1,3 and β-1,4 β- d-glucans or lichenan. Differences in the active site region residues of TFs β-glucanase and barley β-glucanase create binding site topographies that require different substrate conformations. In contrast to barley β-glucanase, TFs β-glucanase possesses a unique and compact active site. The structural analysis results suggest that the tyrosine residue, which is conserved in all known 1,3-1,4-β- d-glucanases, is involved in the recognition of mixed β-1,3 and β-1,4 linked polysaccharide.

Exploring the Influence of Diamagnetic Ions on the Mechanism of Magnetization Relaxation in {CoIII2LnIII2} (Ln = Dy, Tb, Ho) "Butterfly" Complexes.

PubMed

Vignesh, Kuduva R; Langley, Stuart K; Murray, Keith S; Rajaraman, Gopalan

2017-03-06

The synthesis and magnetic and theoretical studies of three isostructural heterometallic [Co III 2 Ln III 2 (μ 3 -OH) 2 (o-tol) 4 (mdea) 2 (NO 3 ) 2 ] (Ln = Dy (1), Tb (2), Ho (3)) "butterfly" complexes are reported (o-tol = o-toluate, (mdea) 2- = doubly deprotonated N-methyldiethanolamine). The Co III ions are diamagnetic in these complexes. Analysis of the dc magnetic susceptibility measurements reveal antiferromagnetic exchange coupling between the two Ln III ions for all three complexes. ac magnetic susceptibility measurements reveal single-molecule magnet (SMM) behavior for complex 1, in the absence of an external magnetic field, with an anisotropy barrier U eff of 81.2 cm -1 , while complexes 2 and 3 exhibit field induced SMM behavior, with a U eff value of 34.2 cm -1 for 2. The barrier height for 3 could not be quantified. To understand the experimental observations, we performed DFT and ab initio CASSCF+RASSI-SO calculations to probe the single-ion properties and the nature and magnitude of the Ln III -Ln III magnetic coupling and to develop an understanding of the role the diamagnetic Co III ion plays in the magnetization relaxation. The calculations were able to rationalize the experimental relaxation data for all complexes and strongly suggest that the Co III ion is integral to the observation of SMM behavior in these systems. Thus, we explored further the effect that the diamagnetic Co III ions have on the magnetization blocking of 1. We did this by modeling a dinuclear {Dy III 2 } complex (1a), with the removal of the diamagnetic ions, and three complexes of the types {K I 2 Dy III 2 } (1b), {Zn II 2 Dy III 2 } (1c), and {Ti IV 2 Dy III 2 } (1d), each containing a different diamagnetic ion. We found that the presence of the diamagnetic ions results in larger negative charges on the bridging hydroxides (1b > 1c > 1 > 1d), in comparison to 1a (no diamagnetic ion), which reduces quantum tunneling of magnetization effects, allowing for more desirable SMM characteristics. The results indicate very strong dependence of diamagnetic ions in the magnetization blocking and the magnitude of the energy barriers. Here we propose a synthetic strategy to enhance the energy barrier in lanthanide-based SMMs by incorporating s- and d-block diamagnetic ions. The presented strategy is likely to have implications beyond the single-molecule magnets studied here.

Fluoxetine and norfluoxetine mediated complex drug-drug interactions: in vitro to in vivo correlation of effects on CYP2D6, CYP2C19 and CYP3A4

PubMed Central

Sager, Jennifer E; Lutz, Justin D; Foti, Robert S; Davis, Connie; Kunze, Kent L; Isoherranen, Nina

2014-01-01

Fluoxetine and its circulating metabolite norfluoxetine present a complex multiple inhibitor system that causes reversible or time-dependent inhibition of CYP2D6, CYP3A4, and CYP2C19 in vitro. While significant inhibition of all three enzymes in vivo is predicted, midazolam and lovastatin AUCs were unaffected by two week dosing of fluoxetine whereas dextromethorphan AUC was increased by 27-fold and omeprazole AUC by 7.1-fold. This observed discrepancy between in vitro risk assessment and in vivo DDI profile was rationalized by time-varying dynamic pharmacokinetic models that incorporated circulating concentrations of fluoxetine and norfluoxetine enantiomers, mutual inhibitor-inhibitor interactions and CYP3A4 induction. The dynamic models predicted all DDIs with less than 2-fold error. This study demonstrates that complex drug-drug interactions that involve multiple mechanisms, pathways and inhibitors with their metabolites can be predicted and rationalized via characterization of all the inhibitory species in vitro. PMID:24569517

A novel improved method for analysis of 2D diffusion relaxation data—2D PARAFAC-Laplace decomposition

NASA Astrophysics Data System (ADS)

Tønning, Erik; Polders, Daniel; Callaghan, Paul T.; Engelsen, Søren B.

2007-09-01

This paper demonstrates how the multi-linear PARAFAC model can with advantage be used to decompose 2D diffusion-relaxation correlation NMR spectra prior to 2D-Laplace inversion to the T2- D domain. The decomposition is advantageous for better interpretation of the complex correlation maps as well as for the quantification of extracted T2- D components. To demonstrate the new method seventeen mixtures of wheat flour, starch, gluten, oil and water were prepared and measured with a 300 MHz nuclear magnetic resonance (NMR) spectrometer using a pulsed gradient stimulated echo (PGSTE) pulse sequence followed by a Carr-Purcell-Meiboom-Gill (CPMG) pulse echo train. By varying the gradient strength, 2D diffusion-relaxation data were recorded for each sample. From these double exponentially decaying relaxation data the PARAFAC algorithm extracted two unique diffusion-relaxation components, explaining 99.8% of the variation in the data set. These two components were subsequently transformed to the T2- D domain using 2D-inverse Laplace transformation and quantitatively assigned to the oil and water components of the samples. The oil component was one distinct distribution with peak intensity at D = 3 × 10 -12 m 2 s -1 and T2 = 180 ms. The water component consisted of two broad populations of water molecules with diffusion coefficients and relaxation times centered around correlation pairs: D = 10 -9 m 2 s -1, T2 = 10 ms and D = 3 × 10 -13 m 2 s -1, T2 = 13 ms. Small spurious peaks observed in the inverse Laplace transformation of original complex data were effectively filtered by the PARAFAC decomposition and thus considered artefacts from the complex Laplace transformation. The oil-to-water ratio determined by PARAFAC followed by 2D-Laplace inversion was perfectly correlated with known oil-to-water ratio of the samples. The new method of using PARAFAC prior to the 2D-Laplace inversion proved to have superior potential in analysis of diffusion-relaxation spectra, as it improves not only the interpretation, but also the quantification.

Ultra small angle x-ray scattering in complex mixtures of triacylglycerols

NASA Astrophysics Data System (ADS)

Peyronel, Fernanda; Quinn, Bonnie; Marangoni, Alejandro G.; Pink, David A.

2014-11-01

Ultra-small angle x-ray scattering (USAXS) has been used to elucidate, in situ, the aggregation structure of unsheared model edible oils. Each system comprised one or two solid lipids and a combination of liquid lipids. The 3D nano- to micro-structures of each system were characterized. The length scale investigated, using the Bonse-Hart camera at beamline ID-15D at the Advanced Photon Source, ANL, ranged from 300 Å-10 µm. Using the Unified Fit model, level-1 analysis showed that the scatterers were 2D objects with either a smooth, a rough, or a diffuse surface. These 2D objects had an average radius of gyration Rg1 between 200-1500 Å. Level-2 analysis displayed a slope between -1 and -2. Use of the Guinier-Porod model gave s ≈ 1 thus showing that it was cylinders (TAGwoods) aggregating with fractal dimension 1 ≤ D2 ≤ 2. D2 = 1 is consistent with 1D structures formed from TAGwoods, while D2 = 2 implies that the TAGwoods had formed structures characteristic of diffusion or reaction limited cluster-cluster aggregation (DLCA/RLCA). These aggregates exhibited radii of gyration, Rg2, between 2500 and 6500 Å. Level-3 analyses showed diffuse surfaces, for most of the systems. These interpretations are in accord with theoretical models which studied crystalline nano-platelets (CNPs) coated with nano-scale layers arising from phase separation at the CNP surfaces. These layers could be due to either liquid-liquid phase separation with the CNPs coated, uniformly or non-uniformly, by a diffuse layer of TAGs, or solid-liquid phase separation with the CNPs coated by a rough layer of crystallites. A fundamental understanding of the self-organizing structures arising in these systems helps advance the characterization of fat crystal networks from nanometres to micrometres. This research can be used to design novel fat structures that use healthier fats via nano- and meso-scale structural engineering.

Forest-atmosphere BVOC exchange in diverse and structurally complex canopies: 1-D modeling of a mid-successional forest in northern Michigan

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

Bryan, Alexander M.; Cheng, Susan J.; Ashworth, Kirsti

Foliar emissions of biogenic volatile organic compounds (BVOC)dimportant precursors of tropospheric ozone and secondary organic aerosolsdvary widely by vegetation type. Modeling studies to date typi-cally represent the canopy as a single dominant tree type or a blend of tree types, yet many forests are diverse with trees of varying height. To assess the sensitivity of biogenic emissions to tree height vari-ation, we compare two 1-D canopy model simulations in which BVOC emission potentials are homo-geneous or heterogeneous with canopy depth. The heterogeneous canopy emulates the mid-successional forest at the University of Michigan Biological Station (UMBS). In this case, high-isoprene-emitting fo-liagemore » (e.g., aspen and oak) is constrained to the upper canopy, where higher sunlight availability increases the light-dependent isoprene emission, leading to 34% more isoprene and its oxidation products as compared to the homogeneous simulation. Isoprene declines from aspen mortality are 10% larger when heterogeneity is considered. Overall, our results highlight the importance of adequately representing complexities of forest canopy structure when simulating light-dependent BVOC emissions and chemistry.« less

Dynamic coupling of three hydrodynamic models

NASA Astrophysics Data System (ADS)

Hartnack, J. N.; Philip, G. T.; Rungoe, M.; Smith, G.; Johann, G.; Larsen, O.; Gregersen, J.; Butts, M. B.

2008-12-01

The need for integrated modelling is evidently present within the field of flood management and flood forecasting. Engineers, modellers and managers are faced with flood problems which transcend the classical hydrodynamic fields of urban, river and coastal flooding. Historically the modeller has been faced with having to select one hydrodynamic model to cover all the aspects of the potentially complex dynamics occurring in a flooding situation. Such a single hydrodynamic model does not cover all dynamics of flood modelling equally well. Thus the ideal choice may in fact be a combination of models. Models combining two numerical/hydrodynamic models are becoming more standard, typically these models combine a 1D river model with a 2D overland flow model or alternatively a 1D sewer/collection system model with a 2D overland solver. In complex coastal/urban areas the flood dynamics may include rivers/streams, collection/storm water systems along with the overland flow. The dynamics within all three areas is of the same time scale and there is feedback in the system across the couplings. These two aspects dictate a fully dynamic three way coupling as opposed to running the models sequentially. It will be shown that the main challenges of the three way coupling are time step issues related to the difference in numerical schemes used in the three model components and numerical instabilities caused by the linking of the model components. MIKE FLOOD combines the models MIKE 11, MIKE 21 and MOUSE into one modelling framework which makes it possible to couple any combination of river, urban and overland flow fully dynamically. The MIKE FLOOD framework will be presented with an overview of the coupling possibilities. The flood modelling concept will be illustrated through real life cases in Australia and in Germany. The real life cases reflect dynamics and interactions across all three model components which are not possible to reproduce using a two-way coupling alone. The models comprise 2D inundation modelling, river networks with multiple structures (pumps, weirs, culverts), urban drainage networks as well as dam break modelling. The models were used to quantify the results of storm events or failures (dam break, pumping failures etc) coinciding with high discharge in river system and heavy rainfall. The detailed representation of the flow path through the city allowed a direct assessment of flood risk Thus it is found that the three-way coupled model is a practical and useful tool for integrated flood management.

2D and 3D MOCART scoring systems assessed by 9.4 T high-field MRI correlate with elementary and complex histological scoring systems in a translational model of osteochondral repair.

PubMed

Goebel, L; Zurakowski, D; Müller, A; Pape, D; Cucchiarini, M; Madry, H

2014-10-01

To compare the 2D and 3D MOCART system obtained with 9.4 T high-field magnetic resonance imaging (MRI) for the ex vivo analysis of osteochondral repair in a translational model and to correlate the data with semiquantitative histological analysis. Osteochondral samples representing all levels of repair (sheep medial femoral condyles; n = 38) were scanned in a 9.4 T high-field MRI. The 2D and adapted 3D MOCART systems were used for grading after point allocation to each category. Each score was correlated with corresponding reconstructions between both MOCART systems. Data were next correlated with corresponding categories of an elementary (Wakitani) and a complex (Sellers) histological scoring system as gold standards. Correlations between most 2D and 3D MOCART score categories were high, while mean total point values of 3D MOCART scores tended to be 15.8-16.1 points higher compared to the 2D MOCART scores based on a Bland-Altman analysis. "Defect fill" and "total points" of both MOCART scores correlated with corresponding categories of Wakitani and Sellers scores (all P ≤ 0.05). "Subchondral bone plate" also correlated between 3D MOCART and Sellers scores (P < 0.001). Most categories of the 2D and 3D MOCART systems correlate, while total scores were generally higher using the 3D MOCART system. Structural categories "total points" and "defect fill" can reliably be assessed by 9.4 T MRI evaluation using either system, "subchondral bone plate" using the 3D MOCART score. High-field MRI is valuable to objectively evaluate osteochondral repair in translational settings. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Oblique Photogrammetry Supporting 3d Urban Reconstruction of Complex Scenarios

NASA Astrophysics Data System (ADS)

Toschi, I.; Ramos, M. M.; Nocerino, E.; Menna, F.; Remondino, F.; Moe, K.; Poli, D.; Legat, K.; Fassi, F.

2017-05-01

Accurate 3D city models represent an important source of geospatial information to support various "smart city" applications, such as space management, energy assessment, 3D cartography, noise and pollution mapping as well as disaster management. Even though remarkable progress has been made in recent years, there are still many open issues, especially when it comes to the 3D modelling of complex urban scenarios like historical and densely-built city centres featuring narrow streets and non-conventional building shapes. Most approaches introduce strong building priors/constraints on symmetry and roof typology that penalize urban environments having high variations of roof shapes. Furthermore, although oblique photogrammetry is rapidly maturing, the use of slanted views for façade reconstruction is not completely included in the reconstruction pipeline of state-of-the-art software. This paper aims to investigate state-of-the-art methods for 3D building modelling in complex urban scenarios with the support of oblique airborne images. A reconstruction approach based on roof primitives fitting is tested. Oblique imagery is then exploited to support the manual editing of the generated building models. At the same time, mobile mapping data are collected at cm resolution and then integrated with the aerial ones. All approaches are tested on the historical city centre of Bergamo (Italy).

A new 3D finite element model of the IEC 60318-1 artificial ear: II. Experimental and numerical validation

NASA Astrophysics Data System (ADS)

Bravo, Agustín; Barham, Richard; Ruiz, Mariano; López, Juan Manuel; De Arcas, Guillermo; Alonso, Jesus

2012-12-01

In part I, the feasibility of using three-dimensional (3D) finite elements (FEs) to model the acoustic behaviour of the IEC 60318-1 artificial ear was studied and the numerical approach compared with classical lumped elements modelling. It was shown that by using a more complex acoustic model that took account of thermo-viscous effects, geometric shapes and dimensions, it was possible to develop a realistic model. This model then had clear advantages in comparison with the models based on equivalent circuits using lumped parameters. In fact results from FE modelling produce a better understanding about the physical phenomena produced inside ear simulator couplers, facilitating spatial and temporal visualization of the sound fields produced. The objective of this study (part II) is to extend the investigation by validating the numerical calculations against measurements on an ear simulator conforming to IEC 60318-1. For this purpose, an appropriate commercially available device is taken and a complete 3D FE model developed for it. The numerical model is based on key dimensional data obtained with a non-destructive x-ray inspection technique. Measurements of the acoustic transfer impedance have been carried out on the same device at a national measurement institute using the method embodied in IEC 60318-1. Having accounted for the actual device dimensions, the thermo-viscous effects inside narrow slots and holes and environmental conditions, the results of the numerical modelling were found to be in good agreement with the measured values.

Differential Attenuation of NMR Signals by Complementary Ion-Exchange Resin Beads for De Novo Analysis of Complex Metabolomics Mixtures.

PubMed

Zhang, Bo; Yuan, Jiaqi; Brüschweiler, Rafael

2017-07-12

A primary goal of metabolomics is the characterization of a potentially very large number of metabolites that are part of complex mixtures. Application to biofluids and tissue samples offers insights into biochemical metabolic pathways and their role in health and disease. 1D 1 H and 2D 13 C- 1 H HSQC NMR spectra are most commonly used for this purpose. They yield quantitative information about each proton of the mixture, but do not tell which protons belong to the same molecule. Interpretation requires the use of NMR spectral databases, which naturally limits these investigations to known metabolites. Here, a new method is presented that uses complementary ion exchange resin beads to differentially attenuate 2D NMR cross-peaks that belong to different metabolites. Based on their characteristic attenuation patterns, cross-peaks could be clustered and assigned to individual molecules, including unknown metabolites with multiple spin systems, as demonstrated for a metabolite model mixture and E. coli cell lysate. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evidence of formation of site-selective inclusion complexation between beta-cyclodextrin and poly(ethylene oxide)-block-poly(propylene oxide)- block-poly(ethylene oxide) copolymers.

PubMed

Tsai, Chi-Chun; Zhang, Wen-Bin; Wang, Chien-Lung; Van Horn, Ryan M; Graham, Matthew J; Huang, Jing; Chen, Yongming; Guo, Mingming; Cheng, Stephen Z D

2010-05-28

A series of inclusion complexes of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO-b-PPO-b-PEO) with beta-cyclodextrin (beta-CD) was prepared. Their formation, structure, and dynamics were investigated by solution two-dimensional rotating-frame Overhauser effect spectroscopy (2D ROESY) and one-dimensional (1D) and 2D solid-state (13)C NMR. The inclusion complexes between the PEO-b-PPO-b-PEO copolymers and the beta-CDs were formed in aqueous solution and detected by 2D ROESY. The high efficiency of cross polarization and spin diffusion experiments in (13)C solid-state NMR showed that the mobility of the PPO blocks dramatically decreases after beta-CD complexation, indicating that they are selectively incorporated onto the PPO blocks. The hydrophobic cavities of beta-CD restrict the PPO block mobility, which is evidence of the formation of inclusion complexes in the solid state. The 2D wide-line separation NMR experiments suggested that beta-CDs only thread onto the PPO blocks while forming the inclusion complexes. The stoichiometry of inclusion complexes was studied using (1)H NMR, and a 3:1 (PO unit to beta-CD) was found for all inclusion complexes, which indicated that the number of threaded beta-CDs was only dependent on the molecular weight of the PPO blocks. 1D wide angle x-ray diffraction studies demonstrated that the beta-CD in the inclusion complex formed a channel-like structure that is different from the pure beta-CD crystal structure.

Evidence of formation of site-selective inclusion complexation between β-cyclodextrin and poly(ethylene oxide)-block-poly(propylene oxide)- block-poly(ethylene oxide) copolymers

NASA Astrophysics Data System (ADS)

Tsai, Chi-Chun; Zhang, Wen-Bin; Wang, Chien-Lung; Van Horn, Ryan M.; Graham, Matthew J.; Huang, Jing; Chen, Yongming; Guo, Mingming; Cheng, Stephen Z. D.

2010-05-01

A series of inclusion complexes of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO-b-PPO-b-PEO) with β-cyclodextrin (β-CD) was prepared. Their formation, structure, and dynamics were investigated by solution two-dimensional rotating-frame Overhauser effect spectroscopy (2D ROESY) and one-dimensional (1D) and 2D solid-state C13 NMR. The inclusion complexes between the PEO-b-PPO-b-PEO copolymers and the β-CDs were formed in aqueous solution and detected by 2D ROESY. The high efficiency of cross polarization and spin diffusion experiments in C13 solid-state NMR showed that the mobility of the PPO blocks dramatically decreases after β-CD complexation, indicating that they are selectively incorporated onto the PPO blocks. The hydrophobic cavities of β-CD restrict the PPO block mobility, which is evidence of the formation of inclusion complexes in the solid state. The 2D wide-line separation NMR experiments suggested that β-CDs only thread onto the PPO blocks while forming the inclusion complexes. The stoichiometry of inclusion complexes was studied using H1 NMR, and a 3:1 (PO unit to β-CD) was found for all inclusion complexes, which indicated that the number of threaded β-CDs was only dependent on the molecular weight of the PPO blocks. 1D wide angle x-ray diffraction studies demonstrated that the β-CD in the inclusion complex formed a channel-like structure that is different from the pure β-CD crystal structure.

Numerical and Experimental Study of Transport Phenomena in Directional Solidification of Succinonitrile

NASA Technical Reports Server (NTRS)

de Groh, Henry C., III; Yao, Minwu

1994-01-01

A numerical and experimental study of the growth of succinonitrile (SCN) using a horizontal Bridginan furnace and transparent glass ampoule was conducted. Two experiments were considered: one in which the temperature profile was fixed relative to the ampoule (no-growth case); and a second in which the thermal profile was translated at a constant rate (steady growth case). Measured temperature profiles on the outer surface of the ampoule were used as thermal boundary conditions for the modelling. The apparent heat capacity formulation combined with the variable viscositymeth was used to model the phase change in SeN. Both 2-D and 3-D models were studied and numerical solutions obtained using the commercial finite element code, FIDAP1. Comparison of the numerical results to experimental data showed excellent agreement. The complex 3-D shallow-cavity flow in the melt, differences between 2-D and 3-D models, effects of natural convection on the thermal gradient and shape of the solid/liquid interface, and the sensitivity of simulations to specific assumptions, are also discussed.

Synthesis and photoluminescence properties of silver(I) complexes based on N-benzoyl-L-glutamic acid and N-donor ligands with different flexibility

NASA Astrophysics Data System (ADS)

Yan, Ming-Jie; Feng, Qi; Song, Hui-Hua

2016-05-01

By changing the N-donor ancillary ligand, three novel silver (I) complexes {[Ag(HbzgluO) (4,4‧-bipy)]·H2O}n (1), {[Ag2(HbzgluO)2 (bpe)2]·2H2O}n (2) and {[Ag(HbzgluO)(bpp)]·2H2O}n (3) (H2bzgluO = N-benzoyl-L-glutamic acid, 4,4‧-bipy = 4,4ˊ-bipyridine, bpe = 1,2-di(4-pyridyl)ethane, bpp = 1,3-di(4-pyridyl)propane) were synthesized. Their structures have been determined by single-crystal X-ray diffraction analyses and further characterized by elemental analyses, IR spectra, powder X-ray diffraction (PXRD), and thermogravimetric analyses (TGA). In this study, the N-donor ligands are changed from rigidity (4,4‧-bipy), quasi-flexibility (bpe) to flexibility (bpp), the structures of complexes also change. Complex 1 features a 1D chain structure which is further linked together to construct a 2D supramolecular structure through hydrogen bonds. Complex 2 is a 1D double-chains configuration which eventually forms a 3D supramolecular network via hydrogen bonding interactions. Whereas, complex 3 exhibits a 2D pleated grid structure which is linked by hydrogen bonding interactions into a 3D supramolecular network. The present observations demonstrate that the modulation of coordination polymers with different structures can accomplish by changing the spacer length of N-donor ligands. In addition, the solid-state circular dichroism (CD) spectra indicated that compound 2 exhibited negative cotton effect which originated from the chiral ligands H2bzgluO and the solid-state fluorescence spectra of the three complexes demonstrated the auxiliary ligands have influence on the photoluminescence properties of the complexes.

Cd(II)-coordination polymers based on tetracarboxylic acid and diverse bis(imidazole) ligands: Synthesis, structural diversity and photoluminescence properties

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

Arıcı, Mürsel, E-mail: marici@ogu.edu.tr; Yeşilel, Okan Zafer; Taş, Murat

Three new Cd(II)-coordination polymers, namely, ([Cd{sub 2}(μ{sub 6}-ao{sub 2}btc)(μ-1,5-bipe){sub 2}]·2H{sub 2}O){sub n} (1), ([Cd{sub 2}(μ{sub 6}-ao{sub 2}btc)(μ-1,4-bix){sub 2}]{sub n}·2DMF) (2) and ([Cd{sub 2}(μ{sub 8}-abtc)(μ-1,4-betix)]·DMF·H{sub 2}O){sub n} (3) (ao{sub 2}btc=di-oxygenated form of 3,3′,5,5′-azobenzenetetracarboxylate, 1,5-bipe: 1,5-bis(imidazol-1yl)pentane, 1,4-bix=1,4-bis(imidazol-1ylmethyl)benzene, 1,4-betix=1,4-bis(2-ethylimidazol-1ylmethyl)benzene) were synthesized with 3,3′,5,5′-azobenzenetetracarboxylic acid and flexible, semi-flexible and semi-flexible substituted bis(imidazole) linkers. They were characterized by IR spectroscopy, elemental analysis, single-crystal X-ray diffraction, powder X-ray diffractions (PXRD) and thermal analyses (TG/DTA). Complexes 1–3 exhibited structural diversities depending on flexible, semi-flexible and semi-flexible substituted bis(imidazole) ligands. Complex 1 was 2D structure with 3,6L18 topology. Complex 2 had a 3D pillar-layered framework with the raremore » sqc27 topology. When semi-flexible substituted bis(imidazole) linker was used, 3D framework of complex 3 was obtained with the paddlewheel Cd{sub 2}(CO{sub 2}){sub 4}-type binuclear SBU. Moreover, thermal and photoluminescence properties of the complexes were determined in detailed. - Graphical abstract: In this study, three novel Cd(II)-coordination polymers were synthesized with 3,3′,5,5′-azobenzenetetracarboxylic acid and flexible, semi-flexible and semi-flexible substituted bis(imidazole) linkers. They were characterized by IR spectroscopy, elemental analysis, single-crystal X-ray diffraction, powder X-ray diffractions (PXRD) and thermal analyses (TG/DTA). Complexes 1–3 exhibited structural diversities depending on flexible, semi-flexible and semi-flexible substituted bis(imidazole) ligands. Complex 1 was 2D structure with 3,6L18 topology. Complex 2 had a 3D pillar-layered framework with the rare sqc27 topology. When semi-flexible substituted bis(imidazole) linker was used, 3D framework of complex 3 was obtained with the paddlewheel Cd{sub 2}(CO{sub 2}){sub 4}-type binuclear SBU. - Highlights: • Three new Cd(II)-coordination polymers with azobenzenetetracarboxylic acid and diverse bis(imidazole) linkers. • Complex 1 is 2D structure with 3,6L18 topology. • 3D pillar-layered framework of 2 with the rare sqc27 topology. • 3D framework of 3 with the paddlewheel Cd{sub 2}(CO{sub 2}){sub 4}-type SBU.« less

The research of laryngeal joints to reconstruction and modeling.

PubMed

Zhang, Yi; Shi, Tingchun

2014-01-01

Larynx has a complex structure with joints and multiple functions. In order to study the artificial larynx and artificial auricle scaffold, a three-dimensional digital model of laryngeal joint is established in this paper using MIMICS with its biomechanical properties analyzed and calculated by using the finite element method. This model is based on the CT scanned images of 281 layers with an interlamellar spacing of 1.25 mm. The obtained data are denoised, segmented and smoothed before being loaded into MIMICS. By further optimizations, an accurate and complete 3D model can be obtained. Subsequently, a 3D FEM of the normal larynx joint is performed which allows observations from any dimensions and angles. Compared with natural laryngeal joint, this model has good geometric similarity and mechanically similar throat voicing functions.

The 3D structures of G-quadruplexes of HIV-1 integrase inhibitors: molecular dynamics simulations in aqueous solution and in the gas phase.

PubMed

Li, Ming-Hui; Zhou, Yi-Han; Luo, Quan; Li, Ze-Sheng

2010-04-01

The unimolecular G-quadruplex structures of d(GGGTGGGTGGGTGGGT) (G1) and d(GTGGTGGGTGGGTGGGT) (G2) are known as the potent nanomolar HIV-1 integrase inhibitors, thus investigating the 3D structures of the two sequences is significant for structure-based rational anti-HIV drug design. In this research, based on the experimental data of circular dichroism (CD) spectropolarimetry and electrospray ionization mass spectrometry (ESI-MS), the initial models of G1 and G2 were constructed by molecular modeling method. The modeling structures of G1 and G2 are intramolecular parallel-stranded quadruplex conformation with three guanine tetrads. Particularly, the structure of G2 possesses a T loop residue between the first and the second G residues that are the component of two adjacent same-stranded G-tetrad planes. This structure proposed by us has a very novel geometry and is different from all reported G-quadruplexes. The extended (35 ns) molecular dynamic (MD) simulations for the models indicate that the G-quadruplexes maintain their structures very well in aqueous solution whether the existence of K(+) or NH (4) (+) in the central channel. Furthermore, we perform 500 ns MD simulations for the models in the gas phase. The results show that all the ion-G-quadruplex complexes are maintained during the whole simulations, despite the large magnitude of phosphate-phosphate repulsions. The gas phase MD simulations provide a good explanation to ESI-MS experiments. Our 3D structures for G1 and G2 will assist in understanding geometric formalism of G-quadruplex folding and may be helpful as a platform for rational anti-HIV drug design.

Real-time tumor motion estimation using respiratory surrogate via memory-based learning

NASA Astrophysics Data System (ADS)

Li, Ruijiang; Lewis, John H.; Berbeco, Ross I.; Xing, Lei

2012-08-01

Respiratory tumor motion is a major challenge in radiation therapy for thoracic and abdominal cancers. Effective motion management requires an accurate knowledge of the real-time tumor motion. External respiration monitoring devices (optical, etc) provide a noninvasive, non-ionizing, low-cost and practical approach to obtain the respiratory signal. Due to the highly complex and nonlinear relations between tumor and surrogate motion, its ultimate success hinges on the ability to accurately infer the tumor motion from respiratory surrogates. Given their widespread use in the clinic, such a method is critically needed. We propose to use a powerful memory-based learning method to find the complex relations between tumor motion and respiratory surrogates. The method first stores the training data in memory and then finds relevant data to answer a particular query. Nearby data points are assigned high relevance (or weights) and conversely distant data are assigned low relevance. By fitting relatively simple models to local patches instead of fitting one single global model, it is able to capture highly nonlinear and complex relations between the internal tumor motion and external surrogates accurately. Due to the local nature of weighting functions, the method is inherently robust to outliers in the training data. Moreover, both training and adapting to new data are performed almost instantaneously with memory-based learning, making it suitable for dynamically following variable internal/external relations. We evaluated the method using respiratory motion data from 11 patients. The data set consists of simultaneous measurement of 3D tumor motion and 1D abdominal surface (used as the surrogate signal in this study). There are a total of 171 respiratory traces, with an average peak-to-peak amplitude of ∼15 mm and average duration of ∼115 s per trace. Given only 5 s (roughly one breath) pretreatment training data, the method achieved an average 3D error of 1.5 mm and 95th percentile error of 3.4 mm on unseen test data. The average 3D error was further reduced to 1.4 mm when the model was tuned to its optimal setting for each respiratory trace. In one trace where a few outliers are present in the training data, the proposed method achieved an error reduction of as much as ∼50% compared with the best linear model (1.0 mm versus 2.1 mm). The memory-based learning technique is able to accurately capture the highly complex and nonlinear relations between tumor and surrogate motion in an efficient manner (a few milliseconds per estimate). Furthermore, the algorithm is particularly suitable to handle situations where the training data are contaminated by large errors or outliers. These desirable properties make it an ideal candidate for accurate and robust tumor gating/tracking using respiratory surrogates.

Molecular pathways in the transformation of model discoidal lipoprotein complexes induced by lecithin:cholesterol acyltransferase.

PubMed

Nichols, A V; Blanche, P J; Gong, E L; Shore, V G; Forte, T M

1985-05-17

Incubation (24 h, 37 degrees C) of discoidal complexes of phosphatidylcholine and apolipoprotein A-I (molar ratio 95 +/- 10 egg yolk phosphatidylcholine-apolipoprotein A-I; 10.5 X 4.0 nm, long X short dimension; designated, class 3 complexes) with the ultracentrifugal d greater than 1.21 g/ml fraction transformed the discoidal complexes to a small product with apparent mean hydrated and nonhydrated diameter of 7.8 and 6.6 nm, respectively. Formation of the small product was associated with marked reduction in phosphatidylcholine-apolipoprotein AI molar ratio of the complexes (on average from 95:1 to 45:1). Phospholipase A2 activity of lecithin:cholesterol acyltransferase participated in the depletion process, as evidenced by production of unesterified fatty acids. In the presence of the d greater than 1.21 g/ml fraction or partially purified lecithin:cholesterol acyltransferase and a source of unesterified cholesterol, the small product could be transformed to a core-containing (cholesteryl ester) round product with a hydrated and nonhydrated diameter of 8.6 and 7.5 nm, respectively. By means of cross-linking with dimethylsuberimidate, the protein moiety of the small product was shown to contain primarily two apolipoprotein A-I molecules per particle, while the large product contained three apolipoprotein A-I molecules per particle. The increase in number of apolipoprotein A-I molecules per particle during transformation of the small to the large product appeared to result from fusion of the small particles during core build-up and release of excess apolipoprotein A-I from the fusion product. The results obtained with the model complexes were consistent for the most part with recent observations (Chen, C., Applegate, K., King, W.C., Glomset, J.A., Norum, K.R. and Gjone, E. (1984) J. Lipid Res. 25, 269-282) on the transformation, by lecithin:cholesterol acyltransferase, of the small spherical high-density lipoproteins of patients with familial lecithin:cholesterol acyltransferase deficiency.

Bio-AIMS Collection of Chemoinformatics Web Tools based on Molecular Graph Information and Artificial Intelligence Models.

PubMed

Munteanu, Cristian R; Gonzalez-Diaz, Humberto; Garcia, Rafael; Loza, Mabel; Pazos, Alejandro

2015-01-01

The molecular information encoding into molecular descriptors is the first step into in silico Chemoinformatics methods in Drug Design. The Machine Learning methods are a complex solution to find prediction models for specific biological properties of molecules. These models connect the molecular structure information such as atom connectivity (molecular graphs) or physical-chemical properties of an atom/group of atoms to the molecular activity (Quantitative Structure - Activity Relationship, QSAR). Due to the complexity of the proteins, the prediction of their activity is a complicated task and the interpretation of the models is more difficult. The current review presents a series of 11 prediction models for proteins, implemented as free Web tools on an Artificial Intelligence Model Server in Biosciences, Bio-AIMS (http://bio-aims.udc.es/TargetPred.php). Six tools predict protein activity, two models evaluate drug - protein target interactions and the other three calculate protein - protein interactions. The input information is based on the protein 3D structure for nine models, 1D peptide amino acid sequence for three tools and drug SMILES formulas for two servers. The molecular graph descriptor-based Machine Learning models could be useful tools for in silico screening of new peptides/proteins as future drug targets for specific treatments.

Thalamocortical Projection Neuron and Interneuron Numbers in the Visual Thalamic Nuclei of the Adult C57BL/6 Mouse.

PubMed

Evangelio, Marian; García-Amado, María; Clascá, Francisco

2018-01-01

A key parameter to constrain predictive, bottom-up circuit models of a given brain domain is the number and position of the neuronal populations involved. These include not only the neurons whose bodies reside within the domain, but also the neurons in distant regions that innervate the domain. The mouse visual cortex receives its main subcortical input from the dorsal lateral geniculate nucleus (dLGN) and the lateral posterior (LP) complex of the thalamus. The latter consists of three different nuclei: lateral posterior lateral (LPL), lateral posterior medial rostral (LPMR), and lateral posterior medial caudal (LPMC), each exhibiting specific patterns of connections with the various visual cortical areas. Here, we have determined the number of thalamocortical projection neurons and interneurons in the LP complex and dLGN of the adult C57BL/6 male mouse. We combined Nissl staining and histochemical and immunolabeling methods for consistently delineating nuclei borders, and applied unbiased stereological cell counting methods. Thalamic interneurons were identified using GABA immunolabeling. The C57BL/6 dLGN contains ∼21,200 neurons, while LP complex contains ∼31,000 total neurons. The dLGN and LP are the only nuclei of the mouse dorsal thalamus containing substantial numbers GABA-immunoreactive interneurons. These interneurons, however, are scarcer than previously estimated; they are 5.6% of dLGN neurons and just 1.9% of the LP neurons. It can be thus inferred that the dLGN contains ∼20,000 and the LP complex ∼30,400 thalamocortical projection neurons (∼12,000 in LPL, 15,200 in LPMR, and 4,200 in LPMC). The present dataset is relevant for constraining models of mouse visual thalamocortical circuits, as well as for quantitative comparisons between genetically modified mouse strains, or across species.

Thalamocortical Projection Neuron and Interneuron Numbers in the Visual Thalamic Nuclei of the Adult C57BL/6 Mouse

PubMed Central

Evangelio, Marian; García-Amado, María; Clascá, Francisco

2018-01-01

A key parameter to constrain predictive, bottom-up circuit models of a given brain domain is the number and position of the neuronal populations involved. These include not only the neurons whose bodies reside within the domain, but also the neurons in distant regions that innervate the domain. The mouse visual cortex receives its main subcortical input from the dorsal lateral geniculate nucleus (dLGN) and the lateral posterior (LP) complex of the thalamus. The latter consists of three different nuclei: lateral posterior lateral (LPL), lateral posterior medial rostral (LPMR), and lateral posterior medial caudal (LPMC), each exhibiting specific patterns of connections with the various visual cortical areas. Here, we have determined the number of thalamocortical projection neurons and interneurons in the LP complex and dLGN of the adult C57BL/6 male mouse. We combined Nissl staining and histochemical and immunolabeling methods for consistently delineating nuclei borders, and applied unbiased stereological cell counting methods. Thalamic interneurons were identified using GABA immunolabeling. The C57BL/6 dLGN contains ∼21,200 neurons, while LP complex contains ∼31,000 total neurons. The dLGN and LP are the only nuclei of the mouse dorsal thalamus containing substantial numbers GABA-immunoreactive interneurons. These interneurons, however, are scarcer than previously estimated; they are 5.6% of dLGN neurons and just 1.9% of the LP neurons. It can be thus inferred that the dLGN contains ∼20,000 and the LP complex ∼30,400 thalamocortical projection neurons (∼12,000 in LPL, 15,200 in LPMR, and 4,200 in LPMC). The present dataset is relevant for constraining models of mouse visual thalamocortical circuits, as well as for quantitative comparisons between genetically modified mouse strains, or across species. PMID:29706872

"Let's Get Physical": Advantages of a Physical Model over 3D Computer Models and Textbooks in Learning Imaging Anatomy

ERIC Educational Resources Information Center

Preece, Daniel; Williams, Sarah B.; Lam, Richard; Weller, Renate

2013-01-01

Three-dimensional (3D) information plays an important part in medical and veterinary education. Appreciating complex 3D spatial relationships requires a strong foundational understanding of anatomy and mental 3D visualization skills. Novel learning resources have been introduced to anatomy training to achieve this. Objective evaluation of their…

Sculplexity: Sculptures of Complexity using 3D printing

NASA Astrophysics Data System (ADS)

Reiss, D. S.; Price, J. J.; Evans, T. S.

2013-11-01

We show how to convert models of complex systems such as 2D cellular automata into a 3D printed object. Our method takes into account the limitations inherent to 3D printing processes and materials. Our approach automates the greater part of this task, bypassing the use of CAD software and the need for manual design. As a proof of concept, a physical object representing a modified forest fire model was successfully printed. Automated conversion methods similar to the ones developed here can be used to create objects for research, for demonstration and teaching, for outreach, or simply for aesthetic pleasure. As our outputs can be touched, they may be particularly useful for those with visual disabilities.

Improved performance in CAPRI round 37 using LZerD docking and template-based modeling with combined scoring functions.

PubMed

Peterson, Lenna X; Shin, Woong-Hee; Kim, Hyungrae; Kihara, Daisuke

2018-03-01

We report our group's performance for protein-protein complex structure prediction and scoring in Round 37 of the Critical Assessment of PRediction of Interactions (CAPRI), an objective assessment of protein-protein complex modeling. We demonstrated noticeable improvement in both prediction and scoring compared to previous rounds of CAPRI, with our human predictor group near the top of the rankings and our server scorer group at the top. This is the first time in CAPRI that a server has been the top scorer group. To predict protein-protein complex structures, we used both multi-chain template-based modeling (TBM) and our protein-protein docking program, LZerD. LZerD represents protein surfaces using 3D Zernike descriptors (3DZD), which are based on a mathematical series expansion of a 3D function. Because 3DZD are a soft representation of the protein surface, LZerD is tolerant to small conformational changes, making it well suited to docking unbound and TBM structures. The key to our improved performance in CAPRI Round 37 was to combine multi-chain TBM and docking. As opposed to our previous strategy of performing docking for all target complexes, we used TBM when multi-chain templates were available and docking otherwise. We also describe the combination of multiple scoring functions used by our server scorer group, which achieved the top rank for the scorer phase. © 2017 Wiley Periodicals, Inc.

A series of transition metal-organic frameworks based on a bipyridinium carboxylate ligand: Syntheses, structures and photoluminescent properties

NASA Astrophysics Data System (ADS)

Pei, Ru-Bo; Cao, Ming-Yang; Li, Lin-Ke; Dong, Xi-Yan; Zang, Shuang-Quan

2017-09-01

Based on a bipyridinium carboxylate ligand 1-(3,5-dicarboxy)-benzyl-1,2-di(pyridine-4-yl)ethylene chloride (H2L+Cl-), eight transition metal coordination polymers, namely, {[Zn(L)Cl]ṡ4H2O}n (1), {[Zn(L)H2O]ṡNO3ṡ2H2O}n (2), {[Zn(L) (H2O)]ṡ(NO3)0.5ṡ(Cl)0.5ṡ2H2O}n (3), {[Cd(L)(H2O)(NO3)]ṡ2H2O}n (4), {[Cd1.5(L) (Cl)2]ṡ2H2O}n (5), {[Cu(L)(H2O)]ṡNO3ṡH2O}n (6), {[Cu(HL)2(H2O)2]·Cl2·6H2O}n (7) and {[Ni(L)(H2O)Cl]ṡ4H2O}n (8) have been synthesized and characterized by single-crystal X-ray diffraction analyses. Complexes 1 and 8 display 2D wave-like layer structures with a 3-connected 63 topology. Complexes 2 and 6 demonstrate 3D 2-fold interpenetrating frameworks with uninodal, 3-connected (10,3)-d utp-topology. Another pair of 3D 2-fold interpenetrating frameworks 3 and 4 possess 3-connected, uninodal 103ThSi2 (ths)-topology. Complex 5 shows a 2D layer structure based on the extending of trinuclear Cd(II) subunits. Complex 7 presents 1D double-chain structure, in which the central Cu(II) ions are connected by the partially deprotonated ligand HL. Additionally, powder X-ray diffractions (PXRD) and thermogravimetric analyses of complexes 1-8, as well as the solid-state luminescent properties of d10 metal complexes 1-4 at room temperature have also been discussed.

Kinetic Aspects of Surfactant-Induced Structural Changes of Proteins - Unsolved Problems of Two-State Model for Protein Denaturation -.

PubMed

Takeda, Kunio; Moriyama, Yoshiko

2015-01-01

The kinetic mechanism of surfactant-induced protein denaturation is discussed on the basis of not only stopped-flow kinetic data but also the changes of protein helicities caused by the surfactants and the discontinuous mobility changes of surfactant-protein complexes. For example, the α-helical structures of bovine serum albumin (BSA) are partially disrupted due to the addition of sodium dodecyl sulfate (SDS). Formation of SDS-BSA complex can lead to only four complex types with specific mobilities depending on the surfactant concentration. On the other hand, the apparent rate constant of the structural change of BSA increases with an increase of SDS concentration, indicating that the rate of the structural change becomes fast as the degree of the change increases. When a certain amount of surfactant ions bind to proteins, their native structures transform directly to particular structures without passing through intermediate stages that might be induced due to the binding of fewer amounts of the surfactant ions. Furthermore, this review brings up a question about two-state and three-state models, N⇌D and N⇌D'⇌D (N: native state, D: denatured sate, D': intermediate between N and D), which have been often adopted without hesitation in discussion on general denaturations of proteins. First of all, doubtful is whether any equilibrium relationship exists in such denaturation reactions. It cannot be disregarded that the D states in these models differ depending on the changes of intensities of the denaturing factors. The authors emphasize that the denaturations or the structural changes of proteins should be discussed assuming one-way reaction models with no backward processes rather than assuming the reversible two-state reaction models or similar modified reaction models.

Diffusion Coefficients of Endogenous Cytosolic Proteins from Rabbit Skinned Muscle Fibers

PubMed Central

Carlson, Brian E.; Vigoreaux, Jim O.; Maughan, David W.

2014-01-01

Efflux time courses of endogenous cytosolic proteins were obtained from rabbit psoas muscle fibers skinned in oil and transferred to physiological salt solution. Proteins were separated by gel electrophoresis and compared to load-matched standards for quantitative analysis. A radial diffusion model incorporating the dissociation and dissipation of supramolecular complexes accounts for an initial lag and subsequent efflux of glycolytic and glycogenolytic enzymes. The model includes terms representing protein crowding, myofilament lattice hindrance, and binding to the cytomatrix. Optimization algorithms returned estimates of the apparent diffusion coefficients, D(r,t), that were very low at the onset of diffusion (∼10−10 cm2 s−1) but increased with time as cytosolic protein density, which was initially high, decreased. D(r,t) at later times ranged from 2.11 × 10−7 cm2 s−1 (parvalbumin) to 0.20 × 10−7 cm2 s−1 (phosphofructose kinase), values that are 3.6- to 12.3-fold lower than those predicted in bulk water. The low initial values are consistent with the presence of complexes in situ; the higher later values are consistent with molecular sieving and transient binding of dissociated proteins. Channeling of metabolic intermediates via enzyme complexes may enhance production of adenosine triphosphate at rates beyond that possible with randomly and/or sparsely distributed enzymes, thereby matching supply with demand. PMID:24559981

1D to 3D dimensional crossover in the superconducting transition of the quasi-one-dimensional carbide superconductor Sc3CoC4.

PubMed

He, Mingquan; Wong, Chi Ho; Shi, Dian; Tse, Pok Lam; Scheidt, Ernst-Wilhelm; Eickerling, Georg; Scherer, Wolfgang; Sheng, Ping; Lortz, Rolf

2015-02-25

The transition metal carbide superconductor Sc(3)CoC(4) may represent a new benchmark system of quasi-one-dimensional (quasi-1D) superconducting behavior. We investigate the superconducting transition of a high-quality single crystalline sample by electrical transport experiments. Our data show that the superconductor goes through a complex dimensional crossover below the onset T(c) of 4.5 K. First, a quasi-1D fluctuating superconducting state with finite resistance forms in the [CoC(4)](∞) ribbons which are embedded in a Sc matrix in this material. At lower temperature, the transversal Josephson or proximity coupling of neighboring ribbons establishes a 3D bulk superconducting state. This dimensional crossover is very similar to Tl(2)Mo(6)Se(6), which for a long time has been regarded as the most appropriate model system of a quasi-1D superconductor. Sc(3)CoC(4) appears to be even more in the 1D limit than Tl(2)Mo(6)Se(6).

The precision and reliability evaluation of 3-dimensional printed damaged bone and prosthesis models by stereo lithography appearance

PubMed Central

Zou, Yun; Han, Qing; Weng, Xisheng; Zou, Yongwei; Yang, Yingying; Zhang, Kesong; Yang, Kerong; Xu, Xiaolin; Wang, Chenyu; Qin, Yanguo; Wang, Jincheng

2018-01-01

Abstract Recently, clinical application of 3D printed model was increasing. However, there was no systemic study for confirming the precision and reliability of 3D printed model. Some senior clinical doctors mistrusted its reliability in clinical application. The purpose of this study was to evaluate the precision and reliability of stereolithography appearance (SLA) 3D printed model. Some related parameters were selected to research the reliability of SLA 3D printed model. The computed tomography (CT) data of bone/prosthesis and model were collected and 3D reconstructed. Some anatomical parameters were measured and statistical analysis was performed; the intraclass correlation coefficient (ICC) was used to was used to evaluate the similarity between the model and real bone/prosthesis. the absolute difference (mm) and relative difference (%) were conducted. For prosthesis model, the 3-dimensional error was measured. There was no significant difference in the anatomical parameters except max height (MH) of long bone. All the ICCs were greater than 0.990. The maximum absolute and relative difference were 0.45 mm and 1.10%; The 3-dimensional error analysis showed that positive/minus distance were 0.273 mm/0.237 mm. The application of SLA 3D printed model in diagnosis and treatment process of complex orthopedic disease was reliable and precise. PMID:29419675

The precision and reliability evaluation of 3-dimensional printed damaged bone and prosthesis models by stereo lithography appearance.

PubMed

Zou, Yun; Han, Qing; Weng, Xisheng; Zou, Yongwei; Yang, Yingying; Zhang, Kesong; Yang, Kerong; Xu, Xiaolin; Wang, Chenyu; Qin, Yanguo; Wang, Jincheng

2018-02-01

Recently, clinical application of 3D printed model was increasing. However, there was no systemic study for confirming the precision and reliability of 3D printed model. Some senior clinical doctors mistrusted its reliability in clinical application. The purpose of this study was to evaluate the precision and reliability of stereolithography appearance (SLA) 3D printed model.Some related parameters were selected to research the reliability of SLA 3D printed model. The computed tomography (CT) data of bone/prosthesis and model were collected and 3D reconstructed. Some anatomical parameters were measured and statistical analysis was performed; the intraclass correlation coefficient (ICC) was used to was used to evaluate the similarity between the model and real bone/prosthesis. the absolute difference (mm) and relative difference (%) were conducted. For prosthesis model, the 3-dimensional error was measured.There was no significant difference in the anatomical parameters except max height (MH) of long bone. All the ICCs were greater than 0.990. The maximum absolute and relative difference were 0.45 mm and 1.10%; The 3-dimensional error analysis showed that positive/minus distance were 0.273 mm/0.237 mm.The application of SLA 3D printed model in diagnosis and treatment process of complex orthopedic disease was reliable and precise.

Estimating the Geoelectric Field Using Precomputed EMTFs: Effect of Magnetometer Cadence

NASA Astrophysics Data System (ADS)

Grawe, M.; Butala, M.; Makela, J. J.; Kamalabadi, F.

2017-12-01

Studies that make use of electromagnetic transfer functions (EMTFs) to calculate the surface electric field from a specified surface magnetic field often use historical magnetometer information for validation and comparison purposes. Depending on the data source, the magnetometer cadence is typically between 1 and 60 seconds. It is often implied that a 60 (and sometimes 10) second cadence is acceptable for purposes of geoelectric field calculation using a geophysical model. Here, we quantitatively assess this claim under different geological settings and using models of varying complexity (using uniform/1D/3D EMTFs) across several different space weather events. Conclusions are made about sampling rate sufficiency as a function of local geology and the spectral content of the surface magnetic field.

Three dimensional (3D) microstructure-based finite element modeling of Al-SiC nanolaminates using focused ion beam (FIB) tomography

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

Mayer, Carl R.

Al-SiC nanolaminate composites show promise as high performance coating materials due to their combination of strength and toughness. Although a significant amount of modeling effort has been focused on materials with an idealized flat nanostructure, experimentally these materials exhibit complex undulating layer geometries. This work utilizes FIB tomography to characterize this nanostructure in 3D and finite element modeling to determine the effect that this complex structure has on the mechanical behavior of these materials. A sufficiently large volume was characterized such that a 1 × 2 μm micropillar could be generated from the dataset and compared directly to experimental results.more » The mechanical response from this nanostructure was then compared to pillar models using simplified structures with perfectly flat layers, layers with sinusoidal waviness, and layers with arc segment waviness. The arc segment based layer geometry showed the best agreement with the experimentally determined structure, indicating it would be the most appropriate geometry for future modeling efforts. - Highlights: •FIB tomography was used to determine the structure of an Al-SiC nanolaminate in 3D. •FEM was used to compare the deformation of the nanostructure to experimental results. •Idealized structures from literature were compared to the FIB determined structure. •Arc segment based structures approximated the FIB determined structure most closely.« less

Neurochemical evidence supporting dopamine D1-D2 receptor heteromers in the striatum of the long-tailed macaque: changes following dopaminergic manipulation.

PubMed

Rico, Alberto J; Dopeso-Reyes, Iria G; Martínez-Pinilla, Eva; Sucunza, Diego; Pignataro, Diego; Roda, Elvira; Marín-Ramos, David; Labandeira-García, José L; George, Susan R; Franco, Rafael; Lanciego, José L

2017-05-01

Although it has long been widely accepted that dopamine receptor types D1 and D2 form GPCR heteromers in the striatum, the presence of D1-D2 receptor heteromers has been recently challenged. In an attempt to properly characterize D1-D2 receptor heteromers, here we have used the in situ proximity ligation assay (PLA) in striatal sections comprising the caudate nucleus, the putamen and the core and shell territories of the nucleus accumbens. Experiments were carried out in control macaques as well as in MPTP-treated animals (with and without dyskinesia). Obtained data support the presence of D1-D2 receptor heteromers within all the striatal subdivisions, with the highest abundance in the accumbens shell. Dopamine depletion by MPTP resulted in an increase of D1-D2 density in caudate and putamen which was normalized by levodopa treatment. Two different sizes of heteromers were consistently found, thus suggesting that besides individual heteromers, D1-D2 receptor heteromers are sometimes organized in macromolecular complexes made of a number of D1-D2 heteromers. Furthermore, the PLA technique was combined with different neuronal markers to properly characterize the identities of striatal neurons expressing D1-D2 heteromers. We have found that striatal projection neurons giving rise to either the direct or the indirect basal ganglia pathways expressed D1-D2 heteromers. Interestingly, macromolecular complexes of D1-D2 heteromers were only found within cholinergic interneurons. In summary, here we provide overwhelming proof that D1 and D2 receptors form heteromeric complexes in the macaque striatum, thus representing a very appealing target for a number of brain diseases involving dopamine dysfunction.

Radiosity diffusion model in 3D

NASA Astrophysics Data System (ADS)

Riley, Jason D.; Arridge, Simon R.; Chrysanthou, Yiorgos; Dehghani, Hamid; Hillman, Elizabeth M. C.; Schweiger, Martin

2001-11-01

We present the Radiosity-Diffusion model in three dimensions(3D), as an extension to previous work in 2D. It is a method for handling non-scattering spaces in optically participating media. We present the extension of the model to 3D including an extension to the model to cope with increased complexity of the 3D domain. We show that in 3D more careful consideration must be given to the issues of meshing and visibility to model the transport of light within reasonable computational bounds. We demonstrate the model to be comparable to Monte-Carlo simulations for selected geometries, and show preliminary results of comparisons to measured time-resolved data acquired on resin phantoms.

Bayesian deconvolution and quantification of metabolites in complex 1D NMR spectra using BATMAN.

PubMed

Hao, Jie; Liebeke, Manuel; Astle, William; De Iorio, Maria; Bundy, Jacob G; Ebbels, Timothy M D

2014-01-01

Data processing for 1D NMR spectra is a key bottleneck for metabolomic and other complex-mixture studies, particularly where quantitative data on individual metabolites are required. We present a protocol for automated metabolite deconvolution and quantification from complex NMR spectra by using the Bayesian automated metabolite analyzer for NMR (BATMAN) R package. BATMAN models resonances on the basis of a user-controllable set of templates, each of which specifies the chemical shifts, J-couplings and relative peak intensities for a single metabolite. Peaks are allowed to shift position slightly between spectra, and peak widths are allowed to vary by user-specified amounts. NMR signals not captured by the templates are modeled non-parametrically by using wavelets. The protocol covers setting up user template libraries, optimizing algorithmic input parameters, improving prior information on peak positions, quality control and evaluation of outputs. The outputs include relative concentration estimates for named metabolites together with associated Bayesian uncertainty estimates, as well as the fit of the remainder of the spectrum using wavelets. Graphical diagnostics allow the user to examine the quality of the fit for multiple spectra simultaneously. This approach offers a workflow to analyze large numbers of spectra and is expected to be useful in a wide range of metabolomics studies.

Three-dimensional printed models in congenital heart disease.

PubMed

Cantinotti, Massimiliano; Valverde, Israel; Kutty, Shelby

2017-01-01

The purpose of this article is to discuss technical considerations and current applications of three-dimensional (3D) printing in congenital heart disease (CHD). CHD represent an attractive field for the application of 3D printed models, with consistent progress made in the past decade. Current 3D models are able to reproduce complex cardiac and extra-cardiac anatomy including small details with very limited range of errors (<1 mm), so this tool could be of value in the planning of surgical or percutaneous treatments for selected cases of CHD. However, the steps involved in the building of 3D models, consisting of image acquisition and selection, segmentation, and printing are highly operator dependent. Current 3D models may be rigid or flexible, but unable to reproduce the physiologic variations during the cardiac cycle. Furthermore, high costs and long average segmentation and printing times (18-24 h) limit a more extensive use. There is a need for better standardization of the procedure employed for collection of the images, the segmentation methods and processes, the phase of cardiac cycle used, and in the materials employed for printing. More studies are necessary to evaluate the diagnostic accuracy and cost-effectiveness of 3D printed models in congenital cardiac care.

Three-Dimensional Rotating Wall Vessel-Derived Cell Culture Models for Studying Virus-Host Interactions

PubMed Central

Gardner, Jameson K.; Herbst-Kralovetz, Melissa M.

2016-01-01

The key to better understanding complex virus-host interactions is the utilization of robust three-dimensional (3D) human cell cultures that effectively recapitulate native tissue architecture and model the microenvironment. A lack of physiologically-relevant animal models for many viruses has limited the elucidation of factors that influence viral pathogenesis and of complex host immune mechanisms. Conventional monolayer cell cultures may support viral infection, but are unable to form the tissue structures and complex microenvironments that mimic host physiology and, therefore, limiting their translational utility. The rotating wall vessel (RWV) bioreactor was designed by the National Aeronautics and Space Administration (NASA) to model microgravity and was later found to more accurately reproduce features of human tissue in vivo. Cells grown in RWV bioreactors develop in a low fluid-shear environment, which enables cells to form complex 3D tissue-like aggregates. A wide variety of human tissues (from neuronal to vaginal tissue) have been grown in RWV bioreactors and have been shown to support productive viral infection and physiological meaningful host responses. The in vivo-like characteristics and cellular features of the human 3D RWV-derived aggregates make them ideal model systems to effectively recapitulate pathophysiology and host responses necessary to conduct rigorous basic science, preclinical and translational studies. PMID:27834891

Drosophila Lin-52 Acts in Opposition to Repressive Components of the Myb-MuvB/dREAM Complex

PubMed Central

Lewis, Peter W.; Sahoo, Debashis; Geng, Cuiyun; Bell, Maren

2012-01-01

The Drosophila melanogaster Myb-MuvB/dREAM complex (MMB/dREAM) participates in both the activation and repression of developmentally regulated genes and origins of DNA replication. Mutants in MMB subunits exhibit diverse phenotypes, including lethality, eye defects, reduced fecundity, and sterility. Here, we used P-element excision to generate mutations in lin-52, which encodes the smallest subunit of the MMB/dREAM complex. lin-52 is required for viability, as null mutants die prior to pupariation. The generation of somatic and germ line mutant clones indicates that lin-52 is required for adult eye development and for early embryogenesis via maternal effects. Interestingly, the maternal-effect embryonic lethality, larval lethality, and adult eye defects could be suppressed by mutations in other subunits of the MMB/dREAM complex. These results suggest that a partial MMB/dREAM complex is responsible for the lethality and eye defects of lin-52 mutants. Furthermore, these findings support a model in which the Lin-52 and Myb proteins counteract the repressive activities of the other members of the MMB/dREAM complex at specific genomic loci in a developmentally controlled manner. PMID:22688510

Design of AN Intelligent Individual Evacuation Model for High Rise Building Fires Based on Neural Network Within the Scope of 3d GIS

NASA Astrophysics Data System (ADS)

Atila, U.; Karas, I. R.; Turan, M. K.; Rahman, A. A.

2013-09-01

One of the most dangerous disaster threatening the high rise and complex buildings of today's world including thousands of occupants inside is fire with no doubt. When we consider high population and the complexity of such buildings it is clear to see that performing a rapid and safe evacuation seems hard and human being does not have good memories in case of such disasters like world trade center 9/11. Therefore, it is very important to design knowledge based realtime interactive evacuation methods instead of classical strategies which lack of flexibility. This paper presents a 3D-GIS implementation which simulates the behaviour of an intelligent indoor pedestrian navigation model proposed for a self -evacuation of a person in case of fire. The model is based on Multilayer Perceptron (MLP) which is one of the most preferred artificial neural network architecture in classification and prediction problems. A sample fire scenario following through predefined instructions has been performed on 3D model of the Corporation Complex in Putrajaya (Malaysia) and the intelligent evacuation process has been realized within a proposed 3D-GIS based simulation.

Carboxylate ligands induced structural diversity of zinc(II) coordination polymers based on 3,6-bis(imidazol-1-yl)carbazole: Syntheses, structures and photocatalytic properties

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

Cheng, Hong-Jian, E-mail: hjcheng@cslg.cn; Tang, Hui-Xiang; Shen, Ya-Li

2015-12-15

Solvothermal reactions of Zn(NO{sub 3}){sub 2}·6H{sub 2}O with 3,6-bis(1-imidazolyl)carbazole (3,6-bmcz) and 1,4-benzenedicarboxylic acid (1,4-H{sub 2}bdc), p-phenylenediacetic acid (p-H{sub 2}pda), benzophenone-4,4-dicarboxylic acid (H{sub 2}bpda) afforded three coordination polymers [Zn(1,4-bdc)(3,6-bmcz)]{sub n} (1), {[Zn(p-pda)(3,6-bmcz)]·1.5H_2O}{sub n} (2) and {[Zn(bpda)(3,6-bmcz)]·0.25H_2O}{sub n} (3). Complexes 1–3 were characterized by elemental analysis, IR, powder X-ray diffraction, and single-crystal X-ray diffraction. Complex 1 shows 3D structure with 2D nets inclined polycatenation. Complexes 2 and 3 possess an extended 3D supramolecular architecture based on their respective 2D layers through hydrogen-bonding interactions and the π···π stacking interactions. The solid state luminescent and optical properties of 1–3 at ambient temperature were alsomore » investigated. A comparative study on their photocatalytic activity toward the degradation of methylene blue in polluted water was explored. - Graphical abstract: Reactions of Zn(NO{sub 3}){sub 2} and 3,6-(1-imidazolyl)carbazole with 1,4-benzenedicarboxylic acid, p-phenylenediacetic acid or benzophenone-4,4-dicarboxylic acid afforded three coordination polymers with different topologies and photocatalytic activity. - Highlights: • Reactions of 1,4-H{sub 2}bdc, p-H{sub 2}pda or H{sub 2}bpda with 3,6-bmcz and Zn(II) gave three CPs. • Complex 1 is a 3D entanglement. • Complex 2 or 3 is a 3D supramolecular structure based on different 2D layers. • Complex 2 exhibited good catalytic activity of methylene blue photodegradation.« less

Visualization of the Drosophila dKeap1-CncC interaction on chromatin illumines cooperative, xenobiotic-specific gene activation

PubMed Central

Deng, Huai; Kerppola, Tom K.

2014-01-01

Interactions among transcription factors control their physiological functions by regulating their binding specificities and transcriptional activities. We implement a strategy to visualize directly the genomic loci that are bound by multi-protein complexes in single cells in Drosophila. This method is based on bimolecular fluorescence complementation (BiFC) analysis of protein interactions on polytene chromosomes. Drosophila Keap1 (dKeap1)-CncC complexes localized to the nucleus and bound chromatin loci that were not bound preferentially by dKeap1 or CncC when they were expressed separately. dKeap1 and CncC binding at these loci was enhanced by phenobarbital, but not by tert-butylhydroquinone (tBHQ) or paraquat. Endogenous dKeap1 and CncC activated transcription of the Jheh (Jheh1, Jheh2, Jheh3) and dKeap1 genes at these loci, whereas CncC alone activated other xenobiotic response genes. Ectopic dKeap1 expression increased CncC binding at the Jheh and dKeap1 gene loci and activated their transcription, whereas dKeap1 inhibited CncC binding at other xenobiotic response gene loci and suppressed their transcription. The combinatorial chromatin-binding specificities and transcriptional activities of dKeap1-CncC complexes mediated the selective activation of different sets of genes by different xenobiotic compounds, in part through feed-forward activation of dKeap1 transcription. PMID:25063457

Neuroprotective mechanism of BNG-1 against focal cerebral ischemia: a neuroimaging and neurotrophin study.

PubMed

Chi, Nai-Fang; Liu, Ho-Ling; Yang, Jen-Tsung; Lin, Jr-Rung; Liao, Shu-Li; Peng, Bo-Han; Lee, Yen-Tung; Lee, Tsong-Hai

2014-01-01

BNG-1 is a herb complex used in traditional Chinese medicine to treat stroke. In this study, we attempted to identify the neuroprotective mechanism of BNG-1 by using neuroimaging and neurotrophin analyses of a stroke animal model. Rats were treated with either saline or BNG-1 for 7 d after 60-min middle cerebral artery occlusion by filament model. The temporal change of magnetic resonance (MR) imaging of brain was studied using a 7 Tesla MR imaging (MRI) system and the temporal expressions of neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) in brain were analyzed before operation and at 4 h, 2 d, and 7 d after operation. Compared with the saline group, the BNG-1 group exhibited a smaller infarction volume in the cerebral cortex in T2 image from as early as 4 h to 7 d, less edema in the cortex in diffusion weighted image from 2 to 7 d, earlier reduction of postischemic hyperperfusion in both the cortex and striatum in perfusion image at 4 h, and earlier normalization of the ischemic pattern in the striatum in susceptibility weighted image at 2 d. NT-3 and BDNF levels were higher in the BNG-1 group than the saline group at 7 d. We concluded that the protective effect of BNG-1 against cerebral ischemic injury might act through improving cerebral hemodynamics and recovering neurotrophin generation.

Novel inclusion complex of ibuprofen tromethamine with cyclodextrins: physico-chemical characterization.

PubMed

Al Omari, Mahmoud M; Daraghmeh, Nidal H; El-Barghouthi, Musa I; Zughul, Mohammad B; Chowdhry, Babur Z; Leharne, Stephen A; Badwan, Adnan A

2009-10-15

Guest-host interactions of ibuprofen tromethamine salt (Ibu.T) with native and modified cyclodextrins (CyDs) have been investigated using several techniques, namely phase solubility diagrams (PSDs), proton nuclear magnetic resonance ((1)H NMR), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffractometry (XRPD), scanning-electron microscopy (SEM) and molecular mechanics (MM). From the analysis of PSD data (A(L)-type) it is concluded that the anionic tromethamine salt of ibuprofen (pK(a)=4.55) forms 1:1 soluble complexes with all CyDs investigated in buffered water at pH 7.0, while the neutral form of Ibu forms an insoluble complex with beta-CyD (B(S)-type) in buffered water at pH 2.0. Ibu.T has a lower tendency to complex with beta-CyD (K(11)=58 M(-1) at pH 7.0) compared with the neutral Ibu (K(11)=4200 M(-1)) in water. Complex formation of Ibu.T with beta-CyD (DeltaG(o)=-20.4 kJ/mol) is enthalpy driven (DeltaH(o)=-22.9 kJ/mol) and is accompanied by a small unfavorable entropy (DeltaS(o)=-8.4 J/mol K) change. (1)H NMR studies and MM computations revealed that, on complexation, the hydrophobic central benzene ring of Ibu.T and part of the isobutyl group reside within the beta-CyD cavity leaving the peripheral groups (carboxylate, tromethamine and methyl groups) located near the hydroxyl group networks at either rim of beta-CyD. PSD, (1)H NMR, DSC, FT-IR, XRPD, SEM and MM studies confirmed the formation of Ibu.T/beta-CyD inclusion complex in solution and the solid state.

Including Short Period Constraints In the Construction of Full Waveform Tomographic Models

NASA Astrophysics Data System (ADS)

Roy, C.; Calo, M.; Bodin, T.; Romanowicz, B. A.

2015-12-01

Thanks to the introduction of the Spectral Element Method (SEM) in seismology, which allows accurate computation of the seismic wavefield in complex media, the resolution of regional and global tomographic models has improved in recent years. However, due to computational costs, only long period waveforms are considered, and only long wavelength structure can be constrained. Thus, the resulting 3D models are smooth, and only represent a small volumetric perturbation around a smooth reference model that does not include upper-mantle discontinuities (e.g. MLD, LAB). Extending the computations to shorter periods, necessary for the resolution of smaller scale features, is computationally challenging. In order to overcome these limitations and to account for layered structure in the upper mantle in our full waveform tomography, we include information provided by short period seismic observables (receiver functions and surface wave dispersion), sensitive to sharp boundaries and anisotropic structure respectively. In a first step, receiver functions and dispersion curves are used to generate a number of 1D radially anisotropic shear velocity profiles using a trans-dimensional Markov-chain Monte Carlo (MCMC) algorithm. These 1D profiles include both isotropic and anisotropic discontinuities in the upper mantle (above 300 km depth) beneath selected stationsand are then used to build a 3D starting model for the full waveform tomographic inversion. This model is built after 1) interpolation between the available 1D profiles, and 2) homogeneization of the layered 1D models to obtain an equivalent smooth 3D starting model in the period range of interest for waveform inversion. The waveforms used in the inversion are collected for paths contained in the region of study and filtered at periods longer than 40s. We use the spectral element code "RegSEM" (Cupillard et al., 2012) for forward computations and a quasi-Newton inversion approach in which kernels are computed using normal mode perturbation theory. We present here the first reults of such an approach after successive iterations of a full waveform tomography of the North American continent.

Synthesis and spectroscopy of micro-oxo (O(2)(-))-bridged heme/non-heme diiron complexes: models for the active site of nitric oxide reductase.

PubMed

Wasser, Ian M; Martens, Constantinus F; Verani, Claudio N; Rentschler, Eva; Huang, Hong-Wei; Moënne-Loccoz, Pierre; Zakharov, Lev N; Rheingold, Arnold L; Karlin, Kenneth D

2004-01-26

In this paper, we describe the synthesis and study of a series of heme/non-heme Fe-O-Fe' complexes supported by a porphyrin and the tripodal nitrogen ligand TMPA [TMPA = tris(2-pyridylmethyl)amine]. The complete synthesis of [((6)L)Fe-O-Fe(X)](+) (1) (X = OMe(-) or Cl(-), 69:31 ratio), where (6)L is the dianion of 5-(o-O-[(N,N-bis(2-pyridylmethyl)-2-(6-methoxyl)pyridinemethanamine)phenyl]-10,15,20-tris(2,6-difluorophenyl)porphine, is reported. The crystal structure for 1.PF(6) reveals an intramolecular heme/non-heme diferric complex bridged by an Fe-O-Fe' moiety; 90 degree angle (Fe-O-Fe') = 166.7(3) degrees, and d(Fe.Fe') = 3.556 A. Crystal data for C(70)H(57)ClF(12)Fe(2)N(8)O(3)P (1.PF(6)): triclinic, Ponemacr;, a = 13.185(3) A, b = 14.590 (3) A, c = 16.885(4) A, alpha = 104.219(4) degrees, beta = 91.572(4) degrees, gamma = 107.907(4) degrees, V = 2977.3(11) A(3), Z = 2, T = 150(2) K. Complex 1 (where X = Cl(-)) is further characterized by UV-vis (lambda(max) = 328, 416 (Soret), 569 nm), (1)H NMR (delta 27-24 [TMPA -CH(2)-], 16.1 [pyrrole-H], 15.2-10.5 [PY-3H, PY-5H], 7.9-7.2 [m- and p-phenyl-H], 6.9-5.8 [PY-4H] ppm), resonance Raman (nu(as)(Fe-O-Fe') 844 cm(-)(1)), and Mössbauer (delta(Fe) = 0.47, 0.41 mm/s; deltaE(A) = 1.59, 0.55 mm/s; 80 K) spectroscopies, MALDI-TOF mass spectrometry (m/z 1202), and SQUID susceptometry (J = - 114.82 cm(-)(1), S = 0). We have also synthesized a series of 3-, 4-, and 5-methyl-substituted as well as selectively deuterated TMPA(Fe') complexes and condensed these with the hydroxo complex (F(8))FeOH or (F(8)-d(8))FeOH to yield "untethered" Fe-O-Fe' analogues. Along with selective deuteration of the methylene hydrogens in TMPA, complete (1)H NMR spectroscopic assignments for 1 have been accomplished. The magnetic properties of several of the untethered complexes and a comparison to those of 1 are also presented. Complex 1 and related species represent good structural and spectroscopic models for the heme/non-heme diiron active site in the enzyme nitric oxide reductase.

Three-dimensional printing in congenital heart disease: A systematic review.

PubMed

Lau, Ivan; Sun, Zhonghua

2018-02-17

Three-dimensional (3D) printing has shown great promise in medicine with increasing reports in congenital heart disease (CHD). This systematic review aims to analyse the main clinical applications and accuracy of 3D printing in CHD, as well as to provide an overview of the software tools, time and costs associated with the generation of 3D printed heart models. A search of different databases was conducted to identify studies investigating the application of 3D printing in CHD. Studies based on patient's medical imaging datasets were included for analysis, while reports on in vitro phantom or review articles were excluded from the analysis. A total of 28 studies met selection criteria for inclusion in the review. More than half of the studies were based on isolated case reports with inclusion of 1-12 cases (61%), while 10 studies (36%) focused on the survey of opinion on the usefulness of 3D printing by healthcare professionals, patients, parents of patients and medical students, and the remaining one involved a multicentre study about the clinical value of 3D printed models in surgical planning of CHD. The analysis shows that patient-specific 3D printed models accurately replicate complex cardiac anatomy, improve understanding and knowledge about congenital heart diseases and demonstrate value in preoperative planning and simulation of cardiac or interventional procedures, assist surgical decision-making and intra-operative orientation, and improve patient-doctor communication and medical education. The cost of 3D printing ranges from USD 55 to USD 810. This systematic review shows the usefulness of 3D printed models in congenital heart disease with applications ranging from accurate replication of complex cardiac anatomy and pathology to medical education, preoperative planning and simulation. The additional cost and time required to manufacture the 3D printed models represent the limitations which need to be addressed in future studies. © 2018 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.

Models for the Binary Complex of Bacteriophage T4 Gp59 Helicase Loading Protein. GP32 Single-Stranded DNA-Binding Protein and Ternary Complex with Pseudo-Y Junction DNA

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

Hinerman, Jennifer M.; Dignam, J. David; Mueser, Timothy C.

2012-04-05

The bacteriophage T4 gp59 helicase assembly protein (gp59) is required for loading of gp41 replicative helicase onto DNA protected by gp32 single-stranded DNA-binding protein. The gp59 protein recognizes branched DNA structures found at replication and recombination sites. Binding of gp32 protein (full-length and deletion constructs) to gp59 protein measured by isothermal titration calorimetry demonstrates that the gp32 protein C-terminal A-domain is essential for protein-protein interaction in the absence of DNA. Sedimentation velocity experiments with gp59 protein and gp32ΔB protein (an N-terminal B-domain deletion) show that these proteins are monomers but form a 1:1 complex with a dissociation constant comparable withmore » that determined by isothermal titration calorimetry. Small angle x-ray scattering (SAXS) studies indicate that the gp59 protein is a prolate monomer, consistent with the crystal structure and hydrodynamic properties determined from sedimentation velocity experiments. SAXS experiments also demonstrate that gp32ΔB protein is a prolate monomer with an elongated A-domain protruding from the core. Moreover, fitting structures of gp59 protein and the gp32 core into the SAXS-derived molecular envelope supports a model for the gp59 protein-gp32ΔB protein complex. Our earlier work demonstrated that gp59 protein attracts full-length gp32 protein to pseudo-Y junctions. A model of the gp59 protein-DNA complex, modified to accommodate new SAXS data for the binary complex together with mutational analysis of gp59 protein, is presented in the accompanying article (Dolezal, D., Jones, C. E., Lai, X., Brister, J. R., Mueser, T. C., Nossal, N. G., and Hinton, D. M. (2012) J. Biol. Chem. 287, 18596–18607).« less

Analysis of Hydrogen Atom Abstraction from Ethylbenzene by an FeVO(TAML) Complex.

PubMed

Shen, Longzhu Q; Kundu, Soumen; Collins, Terrence J; Bominaar, Emile L

2017-04-17

It was shown previously (Chem. Eur. J. 2015, 21, 1803) that the rate of hydrogen atom abstraction, k, from ethylbenzene (EB) by TAML complex [Fe V (O)B*] - (1) in acetonitrile exhibits a large kinetic isotope effect (KIE ∼ 26) in the experimental range 233-243 K. The extrapolated tangents of ln(k/T) vs T -1 plots for EB-d 10 and EB gave a large, negative intercept difference, Int(EB) - Int(EB-d 10 ) = -34.5 J mol -1 K -1 for T -1 → 0, which is shown to be exclusively due to an isotopic mass effect on tunneling. A decomposition of the apparent activation barrier in terms of electronic, ZPE, thermal enthalpic, tunneling, and entropic contributions is presented. Tunneling corrections to ΔH ⧧ and ΔS ⧧ are estimated to be large. The DFT prediction, using functional B3LYP and basis set 6-311G, for the electronic contribution is significantly smaller than suggested by experiment. However, the agreement improves after correction for the basis set superposition error in the interaction between EB and 1. The kinetic model employed has been used to predict rate constants outside the experimental temperature range, which enabled us to compare the reactivity of 1 with those of other hydrogen abstracting complexes.

Complementarity of Historic Building Information Modelling and Geographic Information Systems

NASA Astrophysics Data System (ADS)

Yang, X.; Koehl, M.; Grussenmeyer, P.; Macher, H.

2016-06-01

In this paper, we discuss the potential of integrating both semantically rich models from Building Information Modelling (BIM) and Geographical Information Systems (GIS) to build the detailed 3D historic model. BIM contributes to the creation of a digital representation having all physical and functional building characteristics in several dimensions, as e.g. XYZ (3D), time and non-architectural information that are necessary for construction and management of buildings. GIS has potential in handling and managing spatial data especially exploring spatial relationships and is widely used in urban modelling. However, when considering heritage modelling, the specificity of irregular historical components makes it problematic to create the enriched model according to its complex architectural elements obtained from point clouds. Therefore, some open issues limiting the historic building 3D modelling will be discussed in this paper: how to deal with the complex elements composing historic buildings in BIM and GIS environment, how to build the enriched historic model, and why to construct different levels of details? By solving these problems, conceptualization, documentation and analysis of enriched Historic Building Information Modelling are developed and compared to traditional 3D models aimed primarily for visualization.

Design and Characterization of an Acoustically and Structurally Matched 3-D-Printed Model for Transcranial Ultrasound Imaging.

PubMed

Bai, Chen; Ji, Meiling; Bouakaz, Ayache; Zong, Yujin; Wan, Mingxi

2018-05-01

For investigating human transcranial ultrasound imaging (TUI) through the temporal bone, an intact human skull is needed. Since it is complex and expensive to obtain one, it requires that experiments are performed without excision or abrasion of the skull. Besides, to mimic blood circulation for the vessel target, cellulose tubes generally fit the vessel simulation with straight linear features. These issues, which limit experimental studies, can be overcome by designing a 3-D-printed skull model with acoustic and dimensional properties that match a real skull and a vessel model with curve and bifurcation. First, the optimal printing material which matched a real skull in terms of the acoustic attenuation coefficient and sound propagation velocity was identified at 2-MHz frequency, i.e., 7.06 dB/mm and 2168.71 m/s for the skull while 6.98 dB/mm and 2114.72 m/s for the printed material, respectively. After modeling, the average thickness of the temporal bone in the printed skull was about 1.8 mm, while it was to 1.7 mm in the real skull. Then, a vascular phantom was designed with 3-D-printed vessels of low acoustic attenuation (0.6 dB/mm). It was covered with a porcine brain tissue contained within a transparent polyacrylamide gel. After characterizing the acoustic consistency, based on the designed skull model and vascular phantom, vessels with inner diameters of 1 and 0.7 mm were distinguished by resolution enhanced imaging with low frequency. Measurements and imaging results proved that the model and phantom are authentic and viable alternatives, and will be of interest for TUI, high intensity focused ultrasound, or other therapy studies.

Structural insights into the interaction of IL-33 with its receptors.

PubMed

Liu, Xi; Hammel, Michal; He, Yanfeng; Tainer, John A; Jeng, U-Ser; Zhang, Linqi; Wang, Shuying; Wang, Xinquan

2013-09-10

Interleukin (IL)-33 is an important member of the IL-1 family that has pleiotropic activities in innate and adaptive immune responses in host defense and disease. It signals through its ligand-binding primary receptor ST2 and IL-1 receptor accessory protein (IL-1RAcP), both of which are members of the IL-1 receptor family. To clarify the interaction of IL-33 with its receptors, we determined the crystal structure of IL-33 in complex with the ectodomain of ST2 at a resolution of 3.27 Å. Coupled with structure-based mutagenesis and binding assay, the structural results define the molecular mechanism by which ST2 specifically recognizes IL-33. Structural comparison with other ligand-receptor complexes in the IL-1 family indicates that surface-charge complementarity is critical in determining ligand-binding specificity of IL-1 primary receptors. Combined crystallography and small-angle X-ray-scattering studies reveal that ST2 possesses hinge flexibility between the D3 domain and D1D2 module, whereas IL-1RAcP exhibits a rigid conformation in the unbound state in solution. The molecular flexibility of ST2 provides structural insights into domain-level conformational change of IL-1 primary receptors upon ligand binding, and the rigidity of IL-1RAcP explains its inability to bind ligands directly. The solution architecture of IL-33-ST2-IL-1RAcP complex from small-angle X-ray-scattering analysis resembles IL-1β-IL-1RII-IL-1RAcP and IL-1β-IL-1RI-IL-1RAcP crystal structures. The collective results confer IL-33 structure-function relationships, supporting and extending a general model for ligand-receptor assembly and activation in the IL-1 family.

Extending 3D city models with legal information

NASA Astrophysics Data System (ADS)

Frank, A. U.; Fuhrmann, T.; Navratil, G.

2012-10-01

3D city models represent existing physical objects and their topological and functional relations. In everyday life the rights and responsibilities connected to these objects, primarily legally defined rights and obligations but also other socially and culturally established rights, are of importance. The rights and obligations are defined in various laws and it is often difficult to identify the rules applicable for a certain case. The existing 2D cadastres show civil law rights and obligations and plans to extend them to provide information about public law restrictions for land use are in several countries under way. It is tempting to design extensions to the 3D city models to provide information about legal rights in 3D. The paper analyses the different types of information that are needed to reduce conflicts and to facilitate decisions about land use. We identify the role 3D city models augmented with planning information in 3D can play, but do not advocate a general conversion from 2D to 3D for the legal cadastre. Space is not anisotropic and the up/down dimension is practically very different from the two dimensional plane - this difference must be respected when designing spatial information systems. The conclusions are: (1) continue the current regime for ownership of apartments, which is not ownership of a 3D volume, but co-ownership of a building with exclusive use of some rooms; such exclusive use rights could be shown in a 3D city model; (2) ownership of 3D volumes for complex and unusual building situations can be reported in a 3D city model, but are not required everywhere; (3) indicate restrictions for land use and building in 3D city models, with links to the legal sources.

Calibration of 3D ALE finite element model from experiments on friction stir welding of lap joints

NASA Astrophysics Data System (ADS)

Fourment, Lionel; Gastebois, Sabrina; Dubourg, Laurent

2016-10-01

In order to support the design of such a complex process like Friction Stir Welding (FSW) for the aeronautic industry, numerical simulation software requires (1) developing an efficient and accurate Finite Element (F.E.) formulation that allows predicting welding defects, (2) properly modeling the thermo-mechanical complexity of the FSW process and (3) calibrating the F.E. model from accurate measurements from FSW experiments. This work uses a parallel ALE formulation developed in the Forge® F.E. code to model the different possible defects (flashes and worm holes), while pin and shoulder threads are modeled by a new friction law at the tool / material interface. FSW experiments require using a complex tool with scroll on shoulder, which is instrumented for providing sensitive thermal data close to the joint. Calibration of unknown material thermal coefficients, constitutive equations parameters and friction model from measured forces, torques and temperatures is carried out using two F.E. models, Eulerian and ALE, to reach a satisfactory agreement assessed by the proper sensitivity of the simulation to process parameters.

Biomimetic Modeling of Copper Complexes: A Study of Enantioselective Catalytic Oxidation on D-(+)-Catechin and L-( − )-Epicatechin with Copper Complexes

PubMed Central

Mutti, Francesco G.; Pievo, Roberta; Sgobba, Maila; Gullotti, Michele; Santagostini, Laura

2008-01-01

The biomimetic catalytic oxidations of the dinuclear and trinuclear copper(II) complexes versus two catechols, namely, D-(+)-catechin and L-( − )-epicatechin to give the corresponding quinones are reported. The unstable quinones were trapped by the nucleophilic reagent, 3-methyl-2-benzothiazolinone hydrazone (MBTH), and have been calculated the molar absorptivities of the different quinones. The catalytic efficiency is moderate, as inferred by kinetic constants, but the complexes exhibit significant enantio-differentiating ability towards the catechols, albeit for the dinuclear complexes, this enantio-differentiating ability is lower. In all cases, the preferred enantiomeric substrate is D-(+)-catechin to respect the other catechol, because of the spatial disposition of this substrate. PMID:18825268

On the context-dependent scaling of consumer feeding rates.

PubMed

Barrios-O'Neill, Daniel; Kelly, Ruth; Dick, Jaimie T A; Ricciardi, Anthony; MacIsaac, Hugh J; Emmerson, Mark C

2016-06-01

The stability of consumer-resource systems can depend on the form of feeding interactions (i.e. functional responses). Size-based models predict interactions - and thus stability - based on consumer-resource size ratios. However, little is known about how interaction contexts (e.g. simple or complex habitats) might alter scaling relationships. Addressing this, we experimentally measured interactions between a large size range of aquatic predators (4-6400 mg over 1347 feeding trials) and an invasive prey that transitions among habitats: from the water column (3D interactions) to simple and complex benthic substrates (2D interactions). Simple and complex substrates mediated successive reductions in capture rates - particularly around the unimodal optimum - and promoted prey population stability in model simulations. Many real consumer-resource systems transition between 2D and 3D interactions, and along complexity gradients. Thus, Context-Dependent Scaling (CDS) of feeding interactions could represent an unrecognised aspect of food webs, and quantifying the extent of CDS might enhance predictive ecology. © The Authors. Ecology Letters published by CNRS and John Wiley & Sons Ltd.

Mapping the Interaction Anatomy of BmP02 on Kv1.3 Channel

NASA Astrophysics Data System (ADS)

Wu, B.; Wu, B. F.; Feng, Y. J.; Tao, J.; Ji, Y. H.

2016-07-01

The potassium channel Kv 1.3 plays a vital part in the activation of T lymphocytes and is an attractive pharmacological target for autoimmune diseases. BmP02, a 28-residue peptide isolated from Chinese scorpion (Buthus martensi Karsch) venom, is a potent and selective Kv1.3 channel blocker. However, the mechanism through which BmP02 recognizes and inhibits the Kv1.3 channel is still unclear. In the present study, a complex molecular model of Kv1.3-BmP02 was developed by docking analysis and molecular dynamics simulations. From these simulations, it appears the large β-turn (residues 10-16) of BmP02 might be the binding interface with Kv 1.3. These results were confirmed by scanning alanine mutagenesis of BmP02, which identified His9, Lys11 and Lys13, which lie within BmP02’s β-turn, as key residues for interacting with Kv1.3. Based on these results and molecular modeling, two negatively charged residues of Kv1.3, D421 and D422, located in turret region, were predicted to act as the binding site for BmP02. Mutation of these residues reduced sensitivity of Kv 1.3 to BmP02 inhibition, suggesting that electrostatic interactions play a crucial role in Kv1.3-BmP02 interaction. This study revealed the molecular basis of Kv 1.3 recognition by BmP02 venom, and provides a novel interaction model for Kv channel-specific blocker complex, which may help guide future drug-design for Kv1.3-related channelopathies.

Fractional order analysis of Sephadex gel structures: NMR measurements reflecting anomalous diffusion

NASA Astrophysics Data System (ADS)

Magin, Richard L.; Akpa, Belinda S.; Neuberger, Thomas; Webb, Andrew G.

2011-12-01

We report the appearance of anomalous water diffusion in hydrophilic Sephadex gels observed using pulse field gradient (PFG) nuclear magnetic resonance (NMR). The NMR diffusion data was collected using a Varian 14.1 Tesla imaging system with a home-built RF saddle coil. A fractional order analysis of the data was used to characterize heterogeneity in the gels for the dynamics of water diffusion in this restricted environment. Several recent studies of anomalous diffusion have used the stretched exponential function to model the decay of the NMR signal, i.e., exp[-( bD) α], where D is the apparent diffusion constant, b is determined the experimental conditions (gradient pulse separation, durations and strength), and α is a measure of structural complexity. In this work, we consider a different case where the spatial Laplacian in the Bloch-Torrey equation is generalized to a fractional order model of diffusivity via a complexity parameter, β, a space constant, μ, and a diffusion coefficient, D. This treatment reverts to the classical result for the integer order case. The fractional order decay model was fit to the diffusion-weighted signal attenuation for a range of b-values (0 < b < 4000 s mm -2). Throughout this range of b values, the parameters β, μ and D, were found to correlate with the porosity and tortuosity of the gel structure.

Kinetics of the iodine- and bromine-mediated transport of halide ions: demonstration of an interfacial complexation mechanism.

PubMed Central

Klotz, K H; Benz, R

1993-01-01

Stationary and kinetic experiments were performed on lipid bilayer membranes to study the mechanism of iodine- and bromine-mediated halide transport in detail. The stationary conductance data suggested that four different 1:1 complexes between I2 and Br2 and the halides I- and Br- were responsible for the observed conductance increase by iodine and bromine (I3-, I2Br-, Br2I-, and Br3-). Charge pulse experiments allowed the further elucidation of the transport mechanism. Only two of three exponential voltage relaxations predicted by the Läuger model could be resolved under all experimental conditions. This means that either the heterogeneous complexation reactions kR (association) and kD (dissociation) were too fast to be resolved or that the neutral carriers were always in equilibrium within the membrane. Experiments at different carrier and halide concentrations suggested that the translocation of the neutral carrier is much faster than the other processes involved in carrier-mediated ion transport. The model was modified accordingly. From the charge pulse data at different halide concentrations, the translocation rate constant of the complexed carriers, kAS, the dissociation constant, kD, and the total surface concentration of charged carriers, NAS, could be evaluated from one single charge pulse experiment. The association rate of the complex, kR, could be obtained in some cases from the plot of the stationary conductance data as a function of the halide concentration in the aqueous phase. The translocation rate constant, kAS, of the different complexes is a function of the image force and of the Born charging energy. It increases 5000-fold from Br3- to I3- because of an enlarged ion radius. PMID:8312500

Methode d'identification parametrique pour la surveillance in situ des joints a recouvrement par propagation d'ondes vibratoires

NASA Astrophysics Data System (ADS)

Francoeur, Dany

Cette these de doctorat s'inscrit dans le cadre de projets CRIAQ (Consortium de recherche et d'innovation en aerospatiale du Quebec) orientes vers le developpement d'approches embarquees pour la detection de defauts dans des structures aeronautiques. L'originalite de cette these repose sur le developpement et la validation d'une nouvelle methode de detection, quantification et localisation d'une entaille dans une structure de joint a recouvrement par la propagation d'ondes vibratoires. La premiere partie expose l'etat des connaissances sur l'identification d'un defaut dans le contexte du Structural Health Monitoring (SHM), ainsi que la modelisation de joint a recouvrements. Le chapitre 3 developpe le modele de propagation d'onde d'un joint a recouvrement endommage par une entaille pour une onde de flexion dans la plage des moyennes frequences (10-50 kHz). A cette fin, un modele de transmission de ligne (TLM) est realise pour representer un joint unidimensionnel (1D). Ce modele 1D est ensuite adapte a un joint bi-dimensionnel (2D) en faisant l'hypothese d'un front d'onde plan incident et perpendiculaire au joint. Une methode d'identification parametrique est ensuite developpee pour permettre a la fois la calibration du modele du joint a recouvrement sain, la detection puis la caracterisation de l'entaille situee sur le joint. Cette methode est couplee a un algorithme qui permet une recherche exhaustive de tout l'espace parametrique. Cette technique permet d'extraire une zone d'incertitude reliee aux parametres du modele optimal. Une etude de sensibilite est egalement realisee sur l'identification. Plusieurs resultats de mesure sur des joints a recouvrements 1D et 2D sont realisees permettant ainsi l'etude de la repetabilite des resultats et la variabilite de differents cas d'endommagement. Les resultats de cette etude demontrent d'abord que la methode de detection proposee est tres efficace et permet de suivre la progression d'endommagement. De tres bons resultats de quantification et de localisation d'entailles ont ete obtenus dans les divers joints testes (1D et 2D). Il est prevu que l'utilisation d'ondes de Lamb permettraient d'etendre la plage de validite de la methode pour de plus petits dommages. Ces travaux visent d'abord la surveillance in-situ des structures de joint a recouvrements, mais d'autres types de defauts. (comme les disbond) et. de structures complexes sont egalement envisageables. Mots cles : joint a recouvrement, surveillance in situ, localisation et caracterisation de dommages

Segmentation of Image Data from Complex Organotypic 3D Models of Cancer Tissues with Markov Random Fields

PubMed Central

Robinson, Sean; Guyon, Laurent; Nevalainen, Jaakko; Toriseva, Mervi

2015-01-01

Organotypic, three dimensional (3D) cell culture models of epithelial tumour types such as prostate cancer recapitulate key aspects of the architecture and histology of solid cancers. Morphometric analysis of multicellular 3D organoids is particularly important when additional components such as the extracellular matrix and tumour microenvironment are included in the model. The complexity of such models has so far limited their successful implementation. There is a great need for automatic, accurate and robust image segmentation tools to facilitate the analysis of such biologically relevant 3D cell culture models. We present a segmentation method based on Markov random fields (MRFs) and illustrate our method using 3D stack image data from an organotypic 3D model of prostate cancer cells co-cultured with cancer-associated fibroblasts (CAFs). The 3D segmentation output suggests that these cell types are in physical contact with each other within the model, which has important implications for tumour biology. Segmentation performance is quantified using ground truth labels and we show how each step of our method increases segmentation accuracy. We provide the ground truth labels along with the image data and code. Using independent image data we show that our segmentation method is also more generally applicable to other types of cellular microscopy and not only limited to fluorescence microscopy. PMID:26630674

Segmentation of Image Data from Complex Organotypic 3D Models of Cancer Tissues with Markov Random Fields.

PubMed

Robinson, Sean; Guyon, Laurent; Nevalainen, Jaakko; Toriseva, Mervi; Åkerfelt, Malin; Nees, Matthias

2015-01-01

Organotypic, three dimensional (3D) cell culture models of epithelial tumour types such as prostate cancer recapitulate key aspects of the architecture and histology of solid cancers. Morphometric analysis of multicellular 3D organoids is particularly important when additional components such as the extracellular matrix and tumour microenvironment are included in the model. The complexity of such models has so far limited their successful implementation. There is a great need for automatic, accurate and robust image segmentation tools to facilitate the analysis of such biologically relevant 3D cell culture models. We present a segmentation method based on Markov random fields (MRFs) and illustrate our method using 3D stack image data from an organotypic 3D model of prostate cancer cells co-cultured with cancer-associated fibroblasts (CAFs). The 3D segmentation output suggests that these cell types are in physical contact with each other within the model, which has important implications for tumour biology. Segmentation performance is quantified using ground truth labels and we show how each step of our method increases segmentation accuracy. We provide the ground truth labels along with the image data and code. Using independent image data we show that our segmentation method is also more generally applicable to other types of cellular microscopy and not only limited to fluorescence microscopy.

Syntheses, structural analyses and redox kinetics of four-coordinate [CuL2]2+ and five-coordinate [CuL2(solvent)]2+ complexes (L = 6,6'-dimethyl-2,2'-bipyridine or 2,9-dimethyl-1,10-phenanthroline): completely gated reduction reaction of [Cu(dmp)2]2+ in nitromethane.

PubMed

Itoh, Sumitaka; Kishikawa, Nobuyuki; Suzuki, Takayoshi; Takagi, Hideo D

2005-03-21

[Cu(2,9-dimethyl-1,10-phenanthroline)(2)](2+) and [Cu(6,6'-dimethyl-2,2'-bipyridine)(2)](2+/+) complexes with no coordinated solvent molecule were synthesized and the crystal structures were analyzed: the coordination geometry around the Cu(i) center was in the D(2d) symmetry while a D(2) structure was observed for the four-coordinate Cu(ii) complexes. Coordination of a water or an acetonitrile molecule was found in the trigonal plane of the five-coordinate Cu(ii) complex in the Tbp(trigonal bipyramidal) structure. Spectrophotometric analyses revealed that the D(2) structure of the Cu(ii) complex was retained in nitromethane, although a five-coordinate Tbp species (green in color), was readily formed upon dissolution of the solid (reddish brown) in acetonitrile. The electron self-exchange reaction between D(2d)-Cu(I) and D(2)-Cu(II), observed by the NMR method, was very rapid with k(ex)=(1.1 +/- 0.2) x 10(5) kg mol(-1) s(-1) at 25 degrees C (DeltaH*= 15.6 +/- 1.3 kJ mol(-1) and DeltaS*=-96 +/- 4 J mol(-1) K(-1)), which was more than 10 times larger than that reported for the self-exchange reaction between D(2d)-Cu(I) and Tbp-Cu(II) in acetonitrile. The cross reduction reactions of D(2)-Cu(ii) by ferrocene and decamethylferrocene in nitromethane exhibited a completely gated behavior, while the oxidation reaction of D(2d)-Cu(i) by [Ni(1,4,7-triazacyclononane)(2)](3+) in nitromethane estimated an identically large self-exchange rate constant to that directly obtained by the NMR method. The electron self-exchange rate constant estimated from the oxidation cross reaction in 50% v/v acetonitrile-nitromethane mixture was 10 times smaller than that observed in pure nitromethane. On the basis of the Principle of the Least Motion (PLM) and the Symmetry Rules, it was concluded that gated behaviors observed for the reduction reactions of the five-coordinate Cu(ii)-polypyridine complexes are related to the high-energy C(2v)--> D(2d) conformational change around Cu(ii), and that the electron self-exchange reactions of the Cu(ii)/(i) couples are always adiabatic through the C(2v) structures for both Cu(ii) and Cu(i) since the conformational changes between D(2d), D(2) and C(2v) structures for Cu(i) as well as the conformational change between Tbp and C(2v) structures for Cu(ii) are symmetry-allowed. The completely gated behavior observed for the reduction reactions of D(2)-Cu(ii) species in nitromethane was attributed to the very slow conformational change from the ground-state D(2) to the entatic D(2d) structure that is symmetry-forbidden for d(9) metal complexes: the very slow back reaction, the forbidden conformational change from entatic D(2d) to the ground-state D(2) structure, ensures that the rate of the reduction reaction is independent of the concentration of the reducing reagent.

Crystal Structure of the Vaccinia Virus DNA Polymerase Holoenzyme Subunit D4 in Complex with the A20 N-Terminal Domain

PubMed Central

Contesto-Richefeu, Céline; Tarbouriech, Nicolas; Brazzolotto, Xavier; Betzi, Stéphane; Morelli, Xavier; Burmeister, Wim P.; Iseni, Frédéric

2014-01-01

Vaccinia virus polymerase holoenzyme is composed of the DNA polymerase E9, the uracil-DNA glycosylase D4 and A20, a protein with no known enzymatic activity. The D4/A20 heterodimer is the DNA polymerase co-factor whose function is essential for processive DNA synthesis. Genetic and biochemical data have established that residues located in the N-terminus of A20 are critical for binding to D4. However, no information regarding the residues of D4 involved in A20 binding is yet available. We expressed and purified the complex formed by D4 and the first 50 amino acids of A20 (D4/A201–50). We showed that whereas D4 forms homodimers in solution when expressed alone, D4/A201–50 clearly behaves as a heterodimer. The crystal structure of D4/A201–50 solved at 1.85 Å resolution reveals that the D4/A20 interface (including residues 167 to 180 and 191 to 206 of D4) partially overlaps the previously described D4/D4 dimer interface. A201–50 binding to D4 is mediated by an α-helical domain with important leucine residues located at the very N-terminal end of A20 and a second stretch of residues containing Trp43 involved in stacking interactions with Arg167 and Pro173 of D4. Point mutations of the latter residues disturb D4/A201–50 formation and reduce significantly thermal stability of the complex. Interestingly, small molecule docking with anti-poxvirus inhibitors selected to interfere with D4/A20 binding could reproduce several key features of the D4/A201–50 interaction. Finally, we propose a model of D4/A201–50 in complex with DNA and discuss a number of mutants described in the literature, which affect DNA synthesis. Overall, our data give new insights into the assembly of the poxvirus DNA polymerase cofactor and may be useful for the design and rational improvement of antivirals targeting the D4/A20 interface. PMID:24603707

Rapamycin improves sociability in the BTBR T(+)Itpr3(tf)/J mouse model of autism spectrum disorders.

PubMed

Burket, Jessica A; Benson, Andrew D; Tang, Amy H; Deutsch, Stephen I

2014-01-01

Overactivation of the mammalian target of rapamycin (mTOR) has been implicated in the pathogenesis of syndromic forms of autism spectrum disorders (ASDs), such as tuberous sclerosis complex, neurofibromatosis 1, and fragile X syndrome. Administration of mTORC1 (mTOR complex 1) inhibitors (e.g. rapamycin) in syndromic mouse models of ASDs improved behavior, cognition, and neuropathology. However, since only a minority of ASDs are due to the effects of single genes (∼10%), there is a need to explore inhibition of mTOR activity in mouse models that may be more relevant to the majority of nonsyndromic presentations, such as the genetically inbred BTBR T(+)Itpr3(tf)/J (BTBR) mouse model of ASDs. BTBR mice have social impairment and exhibit increased stereotypic behavior. In prior work, d-cycloserine, a partial glycineB site agonist that targets the N-methyl-d-aspartate (NMDA) receptor, was shown to improve sociability in both Balb/c and BTBR mouse models of ASDs. Importantly, NMDA receptor activation regulates mTOR signaling activity. The current study investigated the ability of rapamycin (10mg/kg, i.p.×four days), an mTORC1 inhibitor, to improve sociability and stereotypic behavior in BTBR mice. Using a standard paradigm to assess mouse social behavior, rapamycin improved several measures of sociability in the BTBR mouse, suggesting that mTOR overactivation represents a therapeutic target that mediates or contributes to impaired sociability in the BTBR mouse model of ASDs. Interestingly, there was no effect of rapamycin on stereotypic behaviors in this mouse model. Copyright © 2013 Elsevier Inc. All rights reserved.

Quantitative analysis of dinuclear manganese(II) EPR spectra

NASA Astrophysics Data System (ADS)

Golombek, Adina P.; Hendrich, Michael P.

2003-11-01

A quantitative method for the analysis of EPR spectra from dinuclear Mn(II) complexes is presented. The complex [(Me 3TACN) 2Mn(II) 2(μ-OAc) 3]BPh 4 ( 1) (Me 3TACN= N, N', N''-trimethyl-1,4,7-triazacyclononane; OAc=acetate 1-; BPh 4=tetraphenylborate 1-) was studied with EPR spectroscopy at X- and Q-band frequencies, for both perpendicular and parallel polarizations of the microwave field, and with variable temperature (2-50 K). Complex 1 is an antiferromagnetically coupled dimer which shows signals from all excited spin manifolds, S=1 to 5. The spectra were simulated with diagonalization of the full spin Hamiltonian which includes the Zeeman and zero-field splittings of the individual manganese sites within the dimer, the exchange and dipolar coupling between the two manganese sites of the dimer, and the nuclear hyperfine coupling for each manganese ion. All possible transitions for all spin manifolds were simulated, with the intensities determined from the calculated probability of each transition. In addition, the non-uniform broadening of all resonances was quantitatively predicted using a lineshape model based on D- and r-strain. As the temperature is increased from 2 K, an 11-line hyperfine pattern characteristic of dinuclear Mn(II) is first observed from the S=3 manifold. D- and r-strain are the dominate broadening effects that determine where the hyperfine pattern will be resolved. A single unique parameter set was found to simulate all spectra arising for all temperatures, microwave frequencies, and microwave modes. The simulations are quantitative, allowing for the first time the determination of species concentrations directly from EPR spectra. Thus, this work describes the first method for the quantitative characterization of EPR spectra of dinuclear manganese centers in model complexes and proteins. The exchange coupling parameter J for complex 1 was determined ( J=-1.5±0.3 cm-1; H ex=-2J S1· S2) and found to be in agreement with a previous determination from magnetization. The phenomenon of exchange striction was found to be insignificant for 1.

Modeling the assembly order of multimeric heteroprotein complexes

PubMed Central

Esquivel-Rodriguez, Juan; Terashi, Genki; Christoffer, Charles; Shin, Woong-Hee

2018-01-01

Protein-protein interactions are the cornerstone of numerous biological processes. Although an increasing number of protein complex structures have been determined using experimental methods, relatively fewer studies have been performed to determine the assembly order of complexes. In addition to the insights into the molecular mechanisms of biological function provided by the structure of a complex, knowing the assembly order is important for understanding the process of complex formation. Assembly order is also practically useful for constructing subcomplexes as a step toward solving the entire complex experimentally, designing artificial protein complexes, and developing drugs that interrupt a critical step in the complex assembly. There are several experimental methods for determining the assembly order of complexes; however, these techniques are resource-intensive. Here, we present a computational method that predicts the assembly order of protein complexes by building the complex structure. The method, named Path-LzerD, uses a multimeric protein docking algorithm that assembles a protein complex structure from individual subunit structures and predicts assembly order by observing the simulated assembly process of the complex. Benchmarked on a dataset of complexes with experimental evidence of assembly order, Path-LZerD was successful in predicting the assembly pathway for the majority of the cases. Moreover, when compared with a simple approach that infers the assembly path from the buried surface area of subunits in the native complex, Path-LZerD has the strong advantage that it can be used for cases where the complex structure is not known. The path prediction accuracy decreased when starting from unbound monomers, particularly for larger complexes of five or more subunits, for which only a part of the assembly path was correctly identified. As the first method of its kind, Path-LZerD opens a new area of computational protein structure modeling and will be an indispensable approach for studying protein complexes. PMID:29329283

Modeling the assembly order of multimeric heteroprotein complexes.

PubMed

Peterson, Lenna X; Togawa, Yoichiro; Esquivel-Rodriguez, Juan; Terashi, Genki; Christoffer, Charles; Roy, Amitava; Shin, Woong-Hee; Kihara, Daisuke

2018-01-01

Protein-protein interactions are the cornerstone of numerous biological processes. Although an increasing number of protein complex structures have been determined using experimental methods, relatively fewer studies have been performed to determine the assembly order of complexes. In addition to the insights into the molecular mechanisms of biological function provided by the structure of a complex, knowing the assembly order is important for understanding the process of complex formation. Assembly order is also practically useful for constructing subcomplexes as a step toward solving the entire complex experimentally, designing artificial protein complexes, and developing drugs that interrupt a critical step in the complex assembly. There are several experimental methods for determining the assembly order of complexes; however, these techniques are resource-intensive. Here, we present a computational method that predicts the assembly order of protein complexes by building the complex structure. The method, named Path-LzerD, uses a multimeric protein docking algorithm that assembles a protein complex structure from individual subunit structures and predicts assembly order by observing the simulated assembly process of the complex. Benchmarked on a dataset of complexes with experimental evidence of assembly order, Path-LZerD was successful in predicting the assembly pathway for the majority of the cases. Moreover, when compared with a simple approach that infers the assembly path from the buried surface area of subunits in the native complex, Path-LZerD has the strong advantage that it can be used for cases where the complex structure is not known. The path prediction accuracy decreased when starting from unbound monomers, particularly for larger complexes of five or more subunits, for which only a part of the assembly path was correctly identified. As the first method of its kind, Path-LZerD opens a new area of computational protein structure modeling and will be an indispensable approach for studying protein complexes.