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Sample records for protein energy landscape

  1. Energy landscape of all-atom protein-protein interactions revealed by multiscale enhanced sampling.

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    Kei Moritsugu

    2014-10-01

    Full Text Available Protein-protein interactions are regulated by a subtle balance of complicated atomic interactions and solvation at the interface. To understand such an elusive phenomenon, it is necessary to thoroughly survey the large configurational space from the stable complex structure to the dissociated states using the all-atom model in explicit solvent and to delineate the energy landscape of protein-protein interactions. In this study, we carried out a multiscale enhanced sampling (MSES simulation of the formation of a barnase-barstar complex, which is a protein complex characterized by an extraordinary tight and fast binding, to determine the energy landscape of atomistic protein-protein interactions. The MSES adopts a multicopy and multiscale scheme to enable for the enhanced sampling of the all-atom model of large proteins including explicit solvent. During the 100-ns MSES simulation of the barnase-barstar system, we observed the association-dissociation processes of the atomistic protein complex in solution several times, which contained not only the native complex structure but also fully non-native configurations. The sampled distributions suggest that a large variety of non-native states went downhill to the stable complex structure, like a fast folding on a funnel-like potential. This funnel landscape is attributed to dominant configurations in the early stage of the association process characterized by near-native orientations, which will accelerate the native inter-molecular interactions. These configurations are guided mostly by the shape complementarity between barnase and barstar, and lead to the fast formation of the final complex structure along the downhill energy landscape.

  2. Exploring the conformational energy landscape of proteins

    Energy Technology Data Exchange (ETDEWEB)

    Nienhaus, G.U. [Univ. of Illinois, Urbana, IL (United States)]|[Universitaet Ulm (Germany); Mueller, J.D.; McMahon, B.H. [Univ. of Illinois, Urbana, IL (United States)] [and others

    1997-04-01

    Proteins possess a complex energy landscape with a large number of local minima called conformational substates that are arranged in a hierarchical fashion. Here we discuss experiments aimed at the elucidation of the energy landscape in carbonmonoxy myoglobin (MbCO). In the highest tier of the hierarchy, a few taxonomic substates exist. Because of their small number, these substates are accessible to detailed structural investigations. Spectroscopic experiments are discussed that elucidate the role of protonations of amino acid side chains in creating the substates. The lower tiers of the hierarchy contain a large number of statistical substates. Substate interconversions are observed in the entire temperature range from below 1 K up to the denaturation temperature, indicating a wide spectrum of energy barriers that separate the substates.

  3. Chemical Denaturants Smoothen Ruggedness on the Free Energy Landscape of Protein Folding.

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    Malhotra, Pooja; Jethva, Prashant N; Udgaonkar, Jayant B

    2017-08-08

    To characterize experimentally the ruggedness of the free energy landscape of protein folding is challenging, because the distributed small free energy barriers are usually dominated by one, or a few, large activation free energy barriers. This study delineates changes in the roughness of the free energy landscape by making use of the observation that a decrease in ruggedness is accompanied invariably by an increase in folding cooperativity. Hydrogen exchange (HX) coupled to mass spectrometry was used to detect transient sampling of local energy minima and the global unfolded state on the free energy landscape of the small protein single-chain monellin. Under native conditions, local noncooperative openings result in interconversions between Boltzmann-distributed intermediate states, populated on an extremely rugged "uphill" energy landscape. The cooperativity of these interconversions was increased by selectively destabilizing the native state via mutations, and further by the addition of a chemical denaturant. The perturbation of stability alone resulted in seven backbone amide sites exchanging cooperatively. The size of the cooperatively exchanging and/or unfolding unit did not depend on the extent of protein destabilization. Only upon the addition of a denaturant to a destabilized mutant variant did seven additional backbone amide sites exchange cooperatively. Segmentwise analysis of the HX kinetics of the mutant variants further confirmed that the observed increase in cooperativity was due to the smoothing of the ruggedness of the free energy landscape of folding of the protein by the chemical denaturant.

  4. Research using energy landscape

    International Nuclear Information System (INIS)

    Kim, Hack Jin

    2007-01-01

    Energy landscape is a theoretical tool used for the study of systems where cooperative processes occur such as liquid, glass, clusters, and protein. Theoretical and experimental researches related to energy landscape are introduced in this review

  5. Multiscale coarse-graining of the protein energy landscape.

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    Ronald D Hills

    2010-06-01

    Full Text Available A variety of coarse-grained (CG models exists for simulation of proteins. An outstanding problem is the construction of a CG model with physically accurate conformational energetics rivaling all-atom force fields. In the present work, atomistic simulations of peptide folding and aggregation equilibria are force-matched using multiscale coarse-graining to develop and test a CG interaction potential of general utility for the simulation of proteins of arbitrary sequence. The reduced representation relies on multiple interaction sites to maintain the anisotropic packing and polarity of individual sidechains. CG energy landscapes computed from replica exchange simulations of the folding of Trpzip, Trp-cage and adenylate kinase resemble those of other reduced representations; non-native structures are observed with energies similar to those of the native state. The artifactual stabilization of misfolded states implies that non-native interactions play a deciding role in deviations from ideal funnel-like cooperative folding. The role of surface tension, backbone hydrogen bonding and the smooth pairwise CG landscape is discussed. Ab initio folding aside, the improved treatment of sidechain rotamers results in stability of the native state in constant temperature simulations of Trpzip, Trp-cage, and the open to closed conformational transition of adenylate kinase, illustrating the potential value of the CG force field for simulating protein complexes and transitions between well-defined structural states.

  6. Enhanced conformational sampling to visualize a free-energy landscape of protein complex formation.

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    Iida, Shinji; Nakamura, Haruki; Higo, Junichi

    2016-06-15

    We introduce various, recently developed, generalized ensemble methods, which are useful to sample various molecular configurations emerging in the process of protein-protein or protein-ligand binding. The methods introduced here are those that have been or will be applied to biomolecular binding, where the biomolecules are treated as flexible molecules expressed by an all-atom model in an explicit solvent. Sampling produces an ensemble of conformations (snapshots) that are thermodynamically probable at room temperature. Then, projection of those conformations to an abstract low-dimensional space generates a free-energy landscape. As an example, we show a landscape of homo-dimer formation of an endothelin-1-like molecule computed using a generalized ensemble method. The lowest free-energy cluster at room temperature coincided precisely with the experimentally determined complex structure. Two minor clusters were also found in the landscape, which were largely different from the native complex form. Although those clusters were isolated at room temperature, with rising temperature a pathway emerged linking the lowest and second-lowest free-energy clusters, and a further temperature increment connected all the clusters. This exemplifies that the generalized ensemble method is a powerful tool for computing the free-energy landscape, by which one can discuss the thermodynamic stability of clusters and the temperature dependence of the cluster networks. © 2016 The Author(s).

  7. Reliable protein folding on non-funneled energy landscapes: the free energy reaction path

    OpenAIRE

    Lois, Gregg; Blawzdziewicz, Jerzy; O'Hern, Corey S.

    2008-01-01

    A theoretical framework is developed to study the dynamics of protein folding. The key insight is that the search for the native protein conformation is influenced by the rate r at which external parameters, such as temperature, chemical denaturant or pH, are adjusted to induce folding. A theory based on this insight predicts that (1) proteins with non-funneled energy landscapes can fold reliably to their native state, (2) reliable folding can occur as an equilibrium or out-of-equilibrium pro...

  8. Autonomously folding protein fragments reveal differences in the energy landscapes of homologous RNases H.

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    Laura E Rosen

    Full Text Available An important approach to understanding how a protein sequence encodes its energy landscape is to compare proteins with different sequences that fold to the same general native structure. In this work, we compare E. coli and T. thermophilus homologs of the protein RNase H. Using protein fragments, we create equilibrium mimics of two different potential partially-folded intermediates (I(core and I(core+1 hypothesized to be present on the energy landscapes of these two proteins. We observe that both T. thermophilus RNase H (ttRNH fragments are folded and have distinct stabilities, indicating that both regions are capable of autonomous folding and that both intermediates are present as local minima on the ttRNH energy landscape. In contrast, the two E. coli RNase H (ecRNH fragments have very similar stabilities, suggesting that the presence of additional residues in the I(core+1 fragment does not affect the folding or structure as compared to I(core. NMR experiments provide additional evidence that only the I(core intermediate is populated by ecRNH. This is one of the biggest differences that has been observed between the energy landscapes of these two proteins. Additionally, we used a FRET experiment in the background of full-length ttRNH to specifically monitor the formation of the I(core+1 intermediate. We determine that the ttRNH I(core+1 intermediate is likely the intermediate populated prior to the rate-limiting barrier to global folding, in contrast to E. coli RNase H for which I(core is the folding intermediate. This result provides new insight into the nature of the rate-limiting barrier for the folding of RNase H.

  9. Electrostatics, structure prediction, and the energy landscapes for protein folding and binding.

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    Tsai, Min-Yeh; Zheng, Weihua; Balamurugan, D; Schafer, Nicholas P; Kim, Bobby L; Cheung, Margaret S; Wolynes, Peter G

    2016-01-01

    While being long in range and therefore weakly specific, electrostatic interactions are able to modulate the stability and folding landscapes of some proteins. The relevance of electrostatic forces for steering the docking of proteins to each other is widely acknowledged, however, the role of electrostatics in establishing specifically funneled landscapes and their relevance for protein structure prediction are still not clear. By introducing Debye-Hückel potentials that mimic long-range electrostatic forces into the Associative memory, Water mediated, Structure, and Energy Model (AWSEM), a transferable protein model capable of predicting tertiary structures, we assess the effects of electrostatics on the landscapes of thirteen monomeric proteins and four dimers. For the monomers, we find that adding electrostatic interactions does not improve structure prediction. Simulations of ribosomal protein S6 show, however, that folding stability depends monotonically on electrostatic strength. The trend in predicted melting temperatures of the S6 variants agrees with experimental observations. Electrostatic effects can play a range of roles in binding. The binding of the protein complex KIX-pKID is largely assisted by electrostatic interactions, which provide direct charge-charge stabilization of the native state and contribute to the funneling of the binding landscape. In contrast, for several other proteins, including the DNA-binding protein FIS, electrostatics causes frustration in the DNA-binding region, which favors its binding with DNA but not with its protein partner. This study highlights the importance of long-range electrostatics in functional responses to problems where proteins interact with their charged partners, such as DNA, RNA, as well as membranes. © 2015 The Protein Society.

  10. Global optimization of proteins using a dynamical lattice model: Ground states and energy landscapes

    OpenAIRE

    Dressel, F.; Kobe, S.

    2004-01-01

    A simple approach is proposed to investigate the protein structure. Using a low complexity model, a simple pairwise interaction and the concept of global optimization, we are able to calculate ground states of proteins, which are in agreement with experimental data. All possible model structures of small proteins are available below a certain energy threshold. The exact lowenergy landscapes for the trp cage protein (1L2Y) is presented showing the connectivity of all states and energy barriers.

  11. From Extraction of Local Structures of Protein Energy Landscapes to Improved Decoy Selection in Template-Free Protein Structure Prediction.

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    Akhter, Nasrin; Shehu, Amarda

    2018-01-19

    Due to the essential role that the three-dimensional conformation of a protein plays in regulating interactions with molecular partners, wet and dry laboratories seek biologically-active conformations of a protein to decode its function. Computational approaches are gaining prominence due to the labor and cost demands of wet laboratory investigations. Template-free methods can now compute thousands of conformations known as decoys, but selecting native conformations from the generated decoys remains challenging. Repeatedly, research has shown that the protein energy functions whose minima are sought in the generation of decoys are unreliable indicators of nativeness. The prevalent approach ignores energy altogether and clusters decoys by conformational similarity. Complementary recent efforts design protein-specific scoring functions or train machine learning models on labeled decoys. In this paper, we show that an informative consideration of energy can be carried out under the energy landscape view. Specifically, we leverage local structures known as basins in the energy landscape probed by a template-free method. We propose and compare various strategies of basin-based decoy selection that we demonstrate are superior to clustering-based strategies. The presented results point to further directions of research for improving decoy selection, including the ability to properly consider the multiplicity of native conformations of proteins.

  12. From Extraction of Local Structures of Protein Energy Landscapes to Improved Decoy Selection in Template-Free Protein Structure Prediction

    Directory of Open Access Journals (Sweden)

    Nasrin Akhter

    2018-01-01

    Full Text Available Due to the essential role that the three-dimensional conformation of a protein plays in regulating interactions with molecular partners, wet and dry laboratories seek biologically-active conformations of a protein to decode its function. Computational approaches are gaining prominence due to the labor and cost demands of wet laboratory investigations. Template-free methods can now compute thousands of conformations known as decoys, but selecting native conformations from the generated decoys remains challenging. Repeatedly, research has shown that the protein energy functions whose minima are sought in the generation of decoys are unreliable indicators of nativeness. The prevalent approach ignores energy altogether and clusters decoys by conformational similarity. Complementary recent efforts design protein-specific scoring functions or train machine learning models on labeled decoys. In this paper, we show that an informative consideration of energy can be carried out under the energy landscape view. Specifically, we leverage local structures known as basins in the energy landscape probed by a template-free method. We propose and compare various strategies of basin-based decoy selection that we demonstrate are superior to clustering-based strategies. The presented results point to further directions of research for improving decoy selection, including the ability to properly consider the multiplicity of native conformations of proteins.

  13. Energy landscapes in proteins and glasses

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    Singh, Sadanand

    Soft materials are ubiquitous in our day-to-day life. They include liquids, colloids, polymers, foams, gels, granular systems, and a number of biological materials. While these materials exhibit a wide range of textures and morphologies, many of their properties have common physicochemical origins. A better understanding of such origins would lead to rational design and engineering of functional soft materials. A common feature of soft materials is the wide range of time and length scales that characterizes their behavior. Unfortunately, available molecular modeling techniques are often ill-suited for problems that exhibit multiple length and time scales. In this thesis, we introduce and implement new simulation methods that have enabled molecular-level studies of soft materials. Such methods permit calculation of free energy surfaces, and we demonstrate their usefulness in the context of proteins and glasses, both of which exhibit rugged free energy landscapes. A first application is concerned with human amylin, a protein associated with Type II diabetes. Patients with Type II diabetes exhibit fibrillar deposits of human amylin protein in the pancreas. By applying the advanced simulation methods and algorithms developed in this work, we investigate the structure and folding dynamics of human amylin. A detailed mechanism is presented at the atomic-level for the nucleation and aggregation of the peptide. The results presented in this work could help in development of therapeutic strategies for Type II diabetes. The second application is concerned with the study of vapor-deposited ultrastable glasses. These stable glasses have, far below the conventional glass transition temperature, the properties expected from the equilibrium supercooled liquid state. Our results indicate that optimal stability is attained when deposition occurs near the Kauzmann temperature. We also show that the extraordinary stability of model vapor deposited glasses is associated with distinct

  14. Protein energy landscapes determined by five-dimensional crystallography

    International Nuclear Information System (INIS)

    Schmidt, Marius; Srajer, Vukica; Henning, Robert; Ihee, Hyotcherl; Purwar, Namrta; Tenboer, Jason; Tripathi, Shailesh

    2013-01-01

    Barriers of activation within the photocycle of a photoactive protein were extracted from comprehensive time courses of time resolved crystallographic data collected at multiple temperature settings. Free-energy landscapes decisively determine the progress of enzymatically catalyzed reactions [Cornish-Bowden (2012 ▶), Fundamentals of Enzyme Kinetics, 4th ed.]. Time-resolved macromolecular crystallography unifies transient-state kinetics with structure determination [Moffat (2001 ▶), Chem. Rev.101, 1569–1581; Schmidt et al. (2005 ▶), Methods Mol. Biol.305, 115–154; Schmidt (2008 ▶), Ultrashort Laser Pulses in Medicine and Biology] because both can be determined from the same set of X-ray data. Here, it is demonstrated how barriers of activation can be determined solely from five-dimensional crystallography, where in addition to space and time, temperature is a variable as well [Schmidt et al. (2010 ▶), Acta Cryst. A66, 198–206]. Directly linking molecular structures with barriers of activation between them allows insight into the structural nature of the barrier to be gained. Comprehensive time series of crystallographic data at 14 different temperature settings were analyzed and the entropy and enthalpy contributions to the barriers of activation were determined. One hundred years after the discovery of X-ray scattering, these results advance X-ray structure determination to a new frontier: the determination of energy landscapes

  15. Role of Electrostatics in Protein-RNA Binding: The Global vs the Local Energy Landscape.

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    Ghaemi, Zhaleh; Guzman, Irisbel; Gnutt, David; Luthey-Schulten, Zaida; Gruebele, Martin

    2017-09-14

    U1A protein-stem loop 2 RNA association is a basic step in the assembly of the spliceosomal U1 small nuclear ribonucleoprotein. Long-range electrostatic interactions due to the positive charge of U1A are thought to provide high binding affinity for the negatively charged RNA. Short range interactions, such as hydrogen bonds and contacts between RNA bases and protein side chains, favor a specific binding site. Here, we propose that electrostatic interactions are as important as local contacts in biasing the protein-RNA energy landscape toward a specific binding site. We show by using molecular dynamics simulations that deletion of two long-range electrostatic interactions (K22Q and K50Q) leads to mutant-specific alternative RNA bound states. One of these states preserves short-range interactions with aromatic residues in the original binding site, while the other one does not. We test the computational prediction with experimental temperature-jump kinetics using a tryptophan probe in the U1A-RNA binding site. The two mutants show the distinct predicted kinetic behaviors. Thus, the stem loop 2 RNA has multiple binding sites on a rough RNA-protein binding landscape. We speculate that the rough protein-RNA binding landscape, when biased to different local minima by electrostatics, could be one way that protein-RNA interactions evolve toward new binding sites and novel function.

  16. Improved free-energy landscape reconstruction of bacteriorhodopsin highlights local variations in unfolding energy.

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    Heenan, Patrick R; Yu, Hao; Siewny, Matthew G W; Perkins, Thomas T

    2018-03-28

    Precisely quantifying the energetics that drive the folding of membrane proteins into a lipid bilayer remains challenging. More than 15 years ago, atomic force microscopy (AFM) emerged as a powerful tool to mechanically extract individual membrane proteins from a lipid bilayer. Concurrently, fluctuation theorems, such as the Jarzynski equality, were applied to deduce equilibrium free energies (ΔG 0 ) from non-equilibrium single-molecule force spectroscopy records. The combination of these two advances in single-molecule studies deduced the free-energy of the model membrane protein bacteriorhodopsin in its native lipid bilayer. To elucidate this free-energy landscape at a higher resolution, we applied two recent developments. First, as an input to the reconstruction, we used force-extension curves acquired with a 100-fold higher time resolution and 10-fold higher force precision than traditional AFM studies of membrane proteins. Next, by using an inverse Weierstrass transform and the Jarzynski equality, we removed the free energy associated with the force probe and determined the molecular free-energy landscape of the molecule under study, bacteriorhodopsin. The resulting landscape yielded an average unfolding free energy per amino acid (aa) of 1.0 ± 0.1 kcal/mol, in agreement with past single-molecule studies. Moreover, on a smaller spatial scale, this high-resolution landscape also agreed with an equilibrium measurement of a particular three-aa transition in bacteriorhodopsin that yielded 2.7 kcal/mol/aa, an unexpectedly high value. Hence, while average unfolding ΔG 0 per aa is a useful metric, the derived high-resolution landscape details significant local variation from the mean. More generally, we demonstrated that, as anticipated, the inverse Weierstrass transform is an efficient means to reconstruct free-energy landscapes from AFM data.

  17. Hierarchical Protein Free Energy Landscapes from Variationally Enhanced Sampling.

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    Shaffer, Patrick; Valsson, Omar; Parrinello, Michele

    2016-12-13

    In recent work, we demonstrated that it is possible to obtain approximate representations of high-dimensional free energy surfaces with variationally enhanced sampling ( Shaffer, P.; Valsson, O.; Parrinello, M. Proc. Natl. Acad. Sci. , 2016 , 113 , 17 ). The high-dimensional spaces considered in that work were the set of backbone dihedral angles of a small peptide, Chignolin, and the high-dimensional free energy surface was approximated as the sum of many two-dimensional terms plus an additional term which represents an initial estimate. In this paper, we build on that work and demonstrate that we can calculate high-dimensional free energy surfaces of very high accuracy by incorporating additional terms. The additional terms apply to a set of collective variables which are more coarse than the base set of collective variables. In this way, it is possible to build hierarchical free energy surfaces, which are composed of terms that act on different length scales. We test the accuracy of these free energy landscapes for the proteins Chignolin and Trp-cage by constructing simple coarse-grained models and comparing results from the coarse-grained model to results from atomistic simulations. The approach described in this paper is ideally suited for problems in which the free energy surface has important features on different length scales or in which there is some natural hierarchy.

  18. PELE:  Protein Energy Landscape Exploration. A Novel Monte Carlo Based Technique.

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    Borrelli, Kenneth W; Vitalis, Andreas; Alcantara, Raul; Guallar, Victor

    2005-11-01

    Combining protein structure prediction algorithms and Metropolis Monte Carlo techniques, we provide a novel method to explore all-atom energy landscapes. The core of the technique is based on a steered localized perturbation followed by side-chain sampling as well as minimization cycles. The algorithm and its application to ligand diffusion are presented here. Ligand exit pathways are successfully modeled for different systems containing ligands of various sizes:  carbon monoxide in myoglobin, camphor in cytochrome P450cam, and palmitic acid in the intestinal fatty-acid-binding protein. These initial applications reveal the potential of this new technique in mapping millisecond-time-scale processes. The computational cost associated with the exploration is significantly less than that of conventional MD simulations.

  19. Protein Folding Free Energy Landscape along the Committor - the Optimal Folding Coordinate.

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    Krivov, Sergei V

    2018-06-06

    Recent advances in simulation and experiment have led to dramatic increases in the quantity and complexity of produced data, which makes the development of automated analysis tools very important. A powerful approach to analyze dynamics contained in such data sets is to describe/approximate it by diffusion on a free energy landscape - free energy as a function of reaction coordinates (RC). For the description to be quantitatively accurate, RCs should be chosen in an optimal way. Recent theoretical results show that such an optimal RC exists; however, determining it for practical systems is a very difficult unsolved problem. Here we describe a solution to this problem. We describe an adaptive nonparametric approach to accurately determine the optimal RC (the committor) for an equilibrium trajectory of a realistic system. In contrast to alternative approaches, which require a functional form with many parameters to approximate an RC and thus extensive expertise with the system, the suggested approach is nonparametric and can approximate any RC with high accuracy without system specific information. To avoid overfitting for a realistically sampled system, the approach performs RC optimization in an adaptive manner by focusing optimization on less optimized spatiotemporal regions of the RC. The power of the approach is illustrated on a long equilibrium atomistic folding simulation of HP35 protein. We have determined the optimal folding RC - the committor, which was confirmed by passing a stringent committor validation test. It allowed us to determine a first quantitatively accurate protein folding free energy landscape. We have confirmed the recent theoretical results that diffusion on such a free energy profile can be used to compute exactly the equilibrium flux, the mean first passage times, and the mean transition path times between any two points on the profile. We have shown that the mean squared displacement along the optimal RC grows linear with time as for

  20. Golf-course and funnel energy landscapes: Protein folding concepts in martensites

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    Shankaraiah, N.

    2017-06-01

    We use protein folding energy landscape concepts such as golf course and funnel to study re-equilibration in athermal martensites under systematic temperature quench Monte Carlo simulations. On quenching below a transition temperature, the seeded high-symmetry parent-phase austenite that converts to the low-symmetry product-phase martensite, through autocatalytic twinning or elastic photocopying, has both rapid conversions and incubation delays in the temperature-time-transformation phase diagram. We find the rapid (incubation delays) conversions at low (high) temperatures arises from the presence of large (small) size of golf-course edge that has the funnel inside for negative energy states. In the incubating state, the strain structure factor enters into the Brillouin-zone golf course through searches for finite transitional pathways which close off at the transition temperature with Vogel-Fulcher divergences that are insensitive to Hamiltonian energy scales and log-normal distributions, as signatures of dominant entropy barriers. The crossing of the entropy barrier is identified through energy occupancy distributions, Monte Carlo acceptance fractions, heat emission, and internal work.

  1. Energy landscape, structure and rate effects on strength properties of alpha-helical proteins

    International Nuclear Information System (INIS)

    Bertaud, Jeremie; Hester, Joshua; Jimenez, Daniel D; Buehler, Markus J

    2010-01-01

    The strength of protein domains is crucial to identify the mechanical role of protein domains in biological processes such as mechanotransduction, tissue mechanics and tissue remodeling. Whereas the concept of strength has been widely investigated for engineered materials, the strength of fundamental protein material building blocks and how it depends on structural parameters such as the chemical bonding, the protein filament length and the timescale of observation or deformation velocity remains poorly understood. Here we report a systematic analysis of the influence of key parameters that define the energy landscape of the strength properties of alpha-helical protein domains, including energy barriers, unfolding and refolding distances, the locations of folded and unfolded states, as well as variations of the length and pulling velocity of alpha-helical protein filaments. The analysis is facilitated by the development of a double-well mesoscale potential formulation, utilized here to carry out a systematic numerical analysis of the behavior of alpha-helices. We compare the results against widely used protein strength models based on the Bell model, one of the simplest models used to characterize the strength of protein filaments. We find that, whereas Bell-type models are a reasonable approximation to describe the rupture of alpha-helical protein domains for a certain range of pulling speeds and values of energy barriers, the model ceases to hold for very large energy barriers and for very small pulling speeds, in agreement with earlier findings. We conclude with an application of our mesoscale model to investigate the effect of the length of alpha-helices on their mechanical strength. We find a weakening effect as the length of alpha-helical proteins increases, followed by an asymptotic regime in which the strength remains constant. We compare strand lengths found in biological proteins with the scaling law of strength versus alpha-helix filament length. The

  2. The energy landscapes of repeat-containing proteins: topology, cooperativity, and the folding funnels of one-dimensional architectures.

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    Diego U Ferreiro

    2008-05-01

    Full Text Available Repeat-proteins are made up of near repetitions of 20- to 40-amino acid stretches. These polypeptides usually fold up into non-globular, elongated architectures that are stabilized by the interactions within each repeat and those between adjacent repeats, but that lack contacts between residues distant in sequence. The inherent symmetries both in primary sequence and three-dimensional structure are reflected in a folding landscape that may be analyzed as a quasi-one-dimensional problem. We present a general description of repeat-protein energy landscapes based on a formal Ising-like treatment of the elementary interaction energetics in and between foldons, whose collective ensemble are treated as spin variables. The overall folding properties of a complete "domain" (the stability and cooperativity of the repeating array can be derived from this microscopic description. The one-dimensional nature of the model implies there are simple relations for the experimental observables: folding free-energy (DeltaG(water and the cooperativity of denaturation (m-value, which do not ordinarily apply for globular proteins. We show how the parameters for the "coarse-grained" description in terms of foldon spin variables can be extracted from more detailed folding simulations on perfectly funneled landscapes. To illustrate the ideas, we present a case-study of a family of tetratricopeptide (TPR repeat proteins and quantitatively relate the results to the experimentally observed folding transitions. Based on the dramatic effect that single point mutations exert on the experimentally observed folding behavior, we speculate that natural repeat proteins are "poised" at particular ratios of inter- and intra-element interaction energetics that allow them to readily undergo structural transitions in physiologically relevant conditions, which may be intrinsically related to their biological functions.

  3. The inverted free energy landscape of an intrinsically disordered peptide by simulations and experiments.

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    Granata, Daniele; Baftizadeh, Fahimeh; Habchi, Johnny; Galvagnion, Celine; De Simone, Alfonso; Camilloni, Carlo; Laio, Alessandro; Vendruscolo, Michele

    2015-10-26

    The free energy landscape theory has been very successful in rationalizing the folding behaviour of globular proteins, as this representation provides intuitive information on the number of states involved in the folding process, their populations and pathways of interconversion. We extend here this formalism to the case of the Aβ40 peptide, a 40-residue intrinsically disordered protein fragment associated with Alzheimer's disease. By using an advanced sampling technique that enables free energy calculations to reach convergence also in the case of highly disordered states of proteins, we provide a precise structural characterization of the free energy landscape of this peptide. We find that such landscape has inverted features with respect to those typical of folded proteins. While the global free energy minimum consists of highly disordered structures, higher free energy regions correspond to a large variety of transiently structured conformations with secondary structure elements arranged in several different manners, and are not separated from each other by sizeable free energy barriers. From this peculiar structure of the free energy landscape we predict that this peptide should become more structured and not only more compact, with increasing temperatures, and we show that this is the case through a series of biophysical measurements.

  4. Energy landscapes in a crowded world

    NARCIS (Netherlands)

    Pasqualetti, Martin; Stremke, Sven

    2018-01-01

    One of the main drivers of landscape transformation has been our demand for energy. We refer to the results of such transformations as "energy landscapes". This paper examines the definition of energy landscapes within a conceptual framework, proposes a classification of energy landscapes, and

  5. Potential energy landscape and robustness of a gene regulatory network: toggle switch.

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    Keun-Young Kim

    2007-03-01

    Full Text Available Finding a multidimensional potential landscape is the key for addressing important global issues, such as the robustness of cellular networks. We have uncovered the underlying potential energy landscape of a simple gene regulatory network: a toggle switch. This was realized by explicitly constructing the steady state probability of the gene switch in the protein concentration space in the presence of the intrinsic statistical fluctuations due to the small number of proteins in the cell. We explored the global phase space for the system. We found that the protein synthesis rate and the unbinding rate of proteins to the gene were small relative to the protein degradation rate; the gene switch is monostable with only one stable basin of attraction. When both the protein synthesis rate and the unbinding rate of proteins to the gene are large compared with the protein degradation rate, two global basins of attraction emerge for a toggle switch. These basins correspond to the biologically stable functional states. The potential energy barrier between the two basins determines the time scale of conversion from one to the other. We found as the protein synthesis rate and protein unbinding rate to the gene relative to the protein degradation rate became larger, the potential energy barrier became larger. This also corresponded to systems with less noise or the fluctuations on the protein numbers. It leads to the robustness of the biological basins of the gene switches. The technique used here is general and can be applied to explore the potential energy landscape of the gene networks.

  6. Energy landscape Allgaeu; Energielandschaft Allgaeu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-04-01

    In tandems with questions on the energy policy turnaround, the topics cultural landscape history, morphology, actual land use, tourism, settlement development or infrastructure are summarized in regional concepts and designs to a consistent landscape. Thus, a true integration of renewable energies in the landscape enhances existing or creates completely new landscape qualities. Energy supply shall be understood as a component of the every day life world. The energy supply shall not be hidden any more, but it rather should be communicated as the brand 'Allgaeu'.

  7. Deciphering hierarchical features in the energy landscape of adenylate kinase folding/unfolding

    Science.gov (United States)

    Taylor, J. Nicholas; Pirchi, Menahem; Haran, Gilad; Komatsuzaki, Tamiki

    2018-03-01

    Hierarchical features of the energy landscape of the folding/unfolding behavior of adenylate kinase, including its dependence on denaturant concentration, are elucidated in terms of single-molecule fluorescence resonance energy transfer (smFRET) measurements in which the proteins are encapsulated in a lipid vesicle. The core in constructing the energy landscape from single-molecule time-series across different denaturant concentrations is the application of rate-distortion theory (RDT), which naturally considers the effects of measurement noise and sampling error, in combination with change-point detection and the quantification of the FRET efficiency-dependent photobleaching behavior. Energy landscapes are constructed as a function of observation time scale, revealing multiple partially folded conformations at small time scales that are situated in a superbasin. As the time scale increases, these denatured states merge into a single basin, demonstrating the coarse-graining of the energy landscape as observation time increases. Because the photobleaching time scale is dependent on the conformational state of the protein, possible nonequilibrium features are discussed, and a statistical test for violation of the detailed balance condition is developed based on the state sequences arising from the RDT framework.

  8. Orientational dynamics and energy landscape features of ...

    Indian Academy of Sciences (India)

    WINTEC

    Energy landscape analysis of inherent structures shows that the ... to be strikingly similar to that of supercooled molecular liquids5 .... where eiα is the α-component (in the space-fixed frame) of the unit orientation vector ei along the principal symmetry axis of the ith ellipsoid of revo- ..... understand pathways of protein folding.

  9. Polyomaviridae Assembly Polymorphism from an Energy Landscape Perspective

    Directory of Open Access Journals (Sweden)

    Karim M. ElSawy

    2008-01-01

    Full Text Available Polyomaviridae assemble in vitro into different aggregates depending on experimental conditions. We use an energy landscape approach using empirical energy calculations to quantify how the formation of these different aggregates depends on pH, the presence of bound calcium ions and disulfide linkages. Computations are carried out for SV40, a member of the Polyomaviridae family and are based on the binding free energy landscape of three distinct trimers of pentamers that correspond to the different bonding configurations between the capsid proteins observed in its crystal structure. Our computational analysis shows that the energetics of one of these environments is pivotal for the polymorphic assembly behaviour of SV40, whilst the binding energy landscapes of the other two environments are broadly funnel-shaped and thus contribute little to the formation of particles other than virus-like particles (VLP. We have quantified how the existence of bound calcium ions in the absence of disulfide linkages enhances the binding free energies of all three environments and hence, favours the assembly of VLPs. Moreover, estimation of the relative binding free energies of the three environments at pH 5 and pH 8 reveals that they are destabilized at pH 5 relative to pH 8. The extent of this destabilization is dependent on the presence of disulfide linkages and bound calcium ions and accounts for the experimentally observed polymorphic behaviour of VP1 proteins at pH 5. Interestingly, concurrent existence of bound calcium ions and disulfide linkages is found to be destabilizing and thus may disrupt the assembly of VLPs at pH 8.

  10. Exploring Energy Landscapes

    Science.gov (United States)

    Wales, David J.

    2018-04-01

    Recent advances in the potential energy landscapes approach are highlighted, including both theoretical and computational contributions. Treating the high dimensionality of molecular and condensed matter systems of contemporary interest is important for understanding how emergent properties are encoded in the landscape and for calculating these properties while faithfully representing barriers between different morphologies. The pathways characterized in full dimensionality, which are used to construct kinetic transition networks, may prove useful in guiding such calculations. The energy landscape perspective has also produced new procedures for structure prediction and analysis of thermodynamic properties. Basin-hopping global optimization, with alternative acceptance criteria and generalizations to multiple metric spaces, has been used to treat systems ranging from biomolecules to nanoalloy clusters and condensed matter. This review also illustrates how all this methodology, developed in the context of chemical physics, can be transferred to landscapes defined by cost functions associated with machine learning.

  11. Energy landscapes, landscapes in transition. How to prepare one's territory to the deployment of renewable energies

    International Nuclear Information System (INIS)

    2014-06-01

    This guide first defines the notion of landscape, outlines what is at stake with decentralised renewable energy production, and presents the various important aspects of a deployment of decentralised renewable energy production. It describes how to define a general strategy for the integration of this production: relationship between energy and landscape, project implementation, partnership, tools to anticipate changes, evolution of social demand through dialogue, conciliation of technical and financial constraints and landscape ambitions. An appendix proposes legal and bibliographical information: legal relationships between energy and landscape, possible arrangements for PLU (plan local d'urbanisme, local urban plan) and SCOT (schema de coherence territoriale, territorial planning document)

  12. Dynamic energy landscapes of riboswitches help interpret conformational rearrangements and function.

    Directory of Open Access Journals (Sweden)

    Giulio Quarta

    Full Text Available Riboswitches are RNAs that modulate gene expression by ligand-induced conformational changes. However, the way in which sequence dictates alternative folding pathways of gene regulation remains unclear. In this study, we compute energy landscapes, which describe the accessible secondary structures for a range of sequence lengths, to analyze the transcriptional process as a given sequence elongates to full length. In line with experimental evidence, we find that most riboswitch landscapes can be characterized by three broad classes as a function of sequence length in terms of the distribution and barrier type of the conformational clusters: low-barrier landscape with an ensemble of different conformations in equilibrium before encountering a substrate; barrier-free landscape in which a direct, dominant "downhill" pathway to the minimum free energy structure is apparent; and a barrier-dominated landscape with two isolated conformational states, each associated with a different biological function. Sharing concepts with the "new view" of protein folding energy landscapes, we term the three sequence ranges above as the sensing, downhill folding, and functional windows, respectively. We find that these energy landscape patterns are conserved in various riboswitch classes, though the order of the windows may vary. In fact, the order of the three windows suggests either kinetic or thermodynamic control of ligand binding. These findings help understand riboswitch structure/function relationships and open new avenues to riboswitch design.

  13. Competing Wind Energy Discourses, Contested Landscapes

    Directory of Open Access Journals (Sweden)

    Antje Otto

    2014-10-01

    Full Text Available The impairment of landscapes is a concern constantly raised against wind energy developments in Germany as in other countries. Often, landscapes or landscape types are treated in the literature as essentialist or at least as uncontested categories. We analyse two examples of local controversies about wind energy, in which “landscape” is employed by supporters and opponents alike, from a poststructuralist and discourse theoretical angle. The aim is to identify and compare landscape constructs produced in the micro discourses of wind energy objectors and proponents at local level (a within each case, (b between the two cases and (c with landscape constructs that were previously found in macro discourses. One major finding is that several different landscapes can exist at one and the same place. Furthermore there seems to be a relatively stable set of competing landscape concepts which is reproduced in specific controversies. The paper concludes by highlighting practical consequences and by identifying promising avenues of further research.

  14. Exploring the free energy landscape: from dynamics to networks and back.

    Directory of Open Access Journals (Sweden)

    Diego Prada-Gracia

    2009-06-01

    Full Text Available Knowledge of the Free Energy Landscape topology is the essential key to understanding many biochemical processes. The determination of the conformers of a protein and their basins of attraction takes a central role for studying molecular isomerization reactions. In this work, we present a novel framework to unveil the features of a Free Energy Landscape answering questions such as how many meta-stable conformers there are, what the hierarchical relationship among them is, or what the structure and kinetics of the transition paths are. Exploring the landscape by molecular dynamics simulations, the microscopic data of the trajectory are encoded into a Conformational Markov Network. The structure of this graph reveals the regions of the conformational space corresponding to the basins of attraction. In addition, handling the Conformational Markov Network, relevant kinetic magnitudes as dwell times and rate constants, or hierarchical relationships among basins, completes the global picture of the landscape. We show the power of the analysis studying a toy model of a funnel-like potential and computing efficiently the conformers of a short peptide, dialanine, paving the way to a systematic study of the Free Energy Landscape in large peptides.

  15. The elastic free energy of a tandem modular protein under force.

    Science.gov (United States)

    Valle-Orero, Jessica; Eckels, Edward C; Stirnemann, Guillaume; Popa, Ionel; Berkovich, Ronen; Fernandez, Julio M

    2015-05-01

    Recent studies have provided a theoretical framework for including entropic elasticity in the free energy landscape of proteins under mechanical force. Accounting for entropic elasticity using polymer physics models has helped explain the hopping behavior seen in single molecule experiments in the low force regime. Here, we expand on the construction of the free energy of a single protein domain under force proposed by Berkovich et al. to provide a free energy landscape for N tandem domains along a continuous polypeptide. Calculation of the free energy of individual domains followed by their concatenation provides a continuous free energy landscape whose curvature is dominated by the worm-like chain at forces below 20 pN. We have validated our free energy model using Brownian dynamics and reproduce key features of protein folding. This free energy model can predict the effects of changes in the elastic properties of a multidomain protein as a consequence of biological modifications such as phosphorylation or the formation of disulfide bonds. This work lays the foundations for the modeling of tissue elasticity, which is largely determined by the properties of tandem polyproteins. Copyright © 2015. Published by Elsevier Inc.

  16. Energy Landscape of Pentapeptides in a Higher-Order (ϕ,ψ Conformational Subspace

    Directory of Open Access Journals (Sweden)

    Karim M. ElSawy

    2016-01-01

    Full Text Available The potential energy landscape of pentapeptides was mapped in a collective coordinate principal conformational subspace derived from principal component analysis of a nonredundant representative set of protein structures from the PDB. Three pentapeptide sequences that are known to be distinct in terms of their secondary structure characteristics, (Ala5, (Gly5, and Val.Asn.Thr.Phe.Val, were considered. Partitioning the landscapes into different energy valleys allowed for calculation of the relative propensities of the peptide secondary structures in a statistical mechanical framework. The distribution of the observed conformations of pentapeptide data showed good correspondence to the topology of the energy landscape of the (Ala5 sequence where, in accord with reported trends, the α-helix showed a predominant propensity at 298 K. The topography of the landscapes indicates that the stabilization of the α-helix in the (Ala5 sequence is enthalpic in nature while entropic factors are important for stabilization of the β-sheet in the Val.Asn.Thr.Phe.Val sequence. The results indicate that local interactions within small pentapeptide segments can lead to conformational preference of one secondary structure over the other where account of conformational entropy is important in order to reveal such preference. The method, therefore, can provide critical structural information for ab initio protein folding methods.

  17. Comparing the Folding and Misfolding Energy Landscapes of Phosphoglycerate Kinase

    OpenAIRE

    Agocs, Gergely; Szabo, Bence T.; Koehler, Gottfried; Osvath, Szabolcs

    2012-01-01

    Partitioning of polypeptides between protein folding and amyloid formation is of outstanding pathophysiological importance. Using yeast phosphoglycerate kinase as model, here we identify the features of the energy landscape that decide the fate of the protein: folding or amyloidogenesis. Structure formation was initiated from the acid-unfolded state, and monitored by fluorescence from 10 ms to 20 days. Solvent conditions were gradually shifted between folding and amyloidogenesis, and the prop...

  18. New interaction paths in the energy landscape: the role of local energy initiatives

    OpenAIRE

    de Boer, Jessica; Zuidema, Christian; Gugerell, Katharina

    2018-01-01

    Energy transition is an encompassing process which not only involves the energy system but also the landscape in which the energy system is embedded. Renewable energy is triggering new interactions with local landscapes in physical, socio-economic and institutional senses. We capture these interactions using the energy landscape concept, which expresses the interdependence of the energy system with the landscape. We aim to understand whether and how local energy initiatives facilitate this in...

  19. Free-energy landscape of protein oligomerization from atomistic simulations

    Science.gov (United States)

    Barducci, Alessandro; Bonomi, Massimiliano; Prakash, Meher K.; Parrinello, Michele

    2013-01-01

    In the realm of protein–protein interactions, the assembly process of homooligomers plays a fundamental role because the majority of proteins fall into this category. A comprehensive understanding of this multistep process requires the characterization of the driving molecular interactions and the transient intermediate species. The latter are often short-lived and thus remain elusive to most experimental investigations. Molecular simulations provide a unique tool to shed light onto these complex processes complementing experimental data. Here we combine advanced sampling techniques, such as metadynamics and parallel tempering, to characterize the oligomerization landscape of fibritin foldon domain. This system is an evolutionarily optimized trimerization motif that represents an ideal model for experimental and computational mechanistic studies. Our results are fully consistent with previous experimental nuclear magnetic resonance and kinetic data, but they provide a unique insight into fibritin foldon assembly. In particular, our simulations unveil the role of nonspecific interactions and suggest that an interplay between thermodynamic bias toward native structure and residual conformational disorder may provide a kinetic advantage. PMID:24248370

  20. Energy landscapes shape animal movement ecology.

    Science.gov (United States)

    Shepard, Emily L C; Wilson, Rory P; Rees, W Gareth; Grundy, Edward; Lambertucci, Sergio A; Vosper, Simon B

    2013-09-01

    The metabolic costs of animal movement have been studied extensively under laboratory conditions, although frequently these are a poor approximation of the costs of operating in the natural, heterogeneous environment. Construction of "energy landscapes," which relate animal locality to the cost of transport, can clarify whether, to what extent, and how movement properties are attributable to environmental heterogeneity. Although behavioral responses to aspects of the energy landscape are well documented in some fields (notably, the selection of tailwinds by aerial migrants) and scales (typically large), the principles of the energy landscape extend across habitat types and spatial scales. We provide a brief synthesis of the mechanisms by which environmentally driven changes in the cost of transport can modulate the behavioral ecology of animal movement in different media, develop example cost functions for movement in heterogeneous environments, present methods for visualizing these energy landscapes, and derive specific predictions of expected outcomes from individual- to population- and species-level processes. Animals modulate a suite of movement parameters (e.g., route, speed, timing of movement, and tortuosity) in relation to the energy landscape, with the nature of their response being related to the energy savings available. Overall, variation in movement costs influences the quality of habitat patches and causes nonrandom movement of individuals between them. This can provide spatial and/or temporal structure to a range of population- and species-level processes, ultimately including gene flow. Advances in animal-attached technology and geographic information systems are opening up new avenues for measuring and mapping energy landscapes that are likely to provide new insight into their influence in animal ecology.

  1. Discrete kinetic models from funneled energy landscape simulations.

    Directory of Open Access Journals (Sweden)

    Nicholas P Schafer

    Full Text Available A general method for facilitating the interpretation of computer simulations of protein folding with minimally frustrated energy landscapes is detailed and applied to a designed ankyrin repeat protein (4ANK. In the method, groups of residues are assigned to foldons and these foldons are used to map the conformational space of the protein onto a set of discrete macrobasins. The free energies of the individual macrobasins are then calculated, informing practical kinetic analysis. Two simple assumptions about the universality of the rate for downhill transitions between macrobasins and the natural local connectivity between macrobasins lead to a scheme for predicting overall folding and unfolding rates, generating chevron plots under varying thermodynamic conditions, and inferring dominant kinetic folding pathways. To illustrate the approach, free energies of macrobasins were calculated from biased simulations of a non-additive structure-based model using two structurally motivated foldon definitions at the full and half ankyrin repeat resolutions. The calculated chevrons have features consistent with those measured in stopped flow chemical denaturation experiments. The dominant inferred folding pathway has an "inside-out", nucleation-propagation like character.

  2. Energy landscape of social balance.

    Science.gov (United States)

    Marvel, Seth A; Strogatz, Steven H; Kleinberg, Jon M

    2009-11-06

    We model a close-knit community of friends and enemies as a fully connected network with positive and negative signs on its edges. Theories from social psychology suggest that certain sign patterns are more stable than others. This notion of social "balance" allows us to define an energy landscape for such networks. Its structure is complex: numerical experiments reveal a landscape dimpled with local minima of widely varying energy levels. We derive rigorous bounds on the energies of these local minima and prove that they have a modular structure that can be used to classify them.

  3. Energy Landscape of Social Balance

    Science.gov (United States)

    Marvel, Seth A.; Strogatz, Steven H.; Kleinberg, Jon M.

    2009-11-01

    We model a close-knit community of friends and enemies as a fully connected network with positive and negative signs on its edges. Theories from social psychology suggest that certain sign patterns are more stable than others. This notion of social “balance” allows us to define an energy landscape for such networks. Its structure is complex: numerical experiments reveal a landscape dimpled with local minima of widely varying energy levels. We derive rigorous bounds on the energies of these local minima and prove that they have a modular structure that can be used to classify them.

  4. Inflation in random landscapes with two energy scales

    Science.gov (United States)

    Blanco-Pillado, Jose J.; Vilenkin, Alexander; Yamada, Masaki

    2018-02-01

    We investigate inflation in a multi-dimensional landscape with a hierarchy of energy scales, motivated by the string theory, where the energy scale of Kahler moduli is usually assumed to be much lower than that of complex structure moduli and dilaton field. We argue that in such a landscape, the dynamics of slow-roll inflation is governed by the low-energy potential, while the initial condition for inflation are determined by tunneling through high-energy barriers. We then use the scale factor cutoff measure to calculate the probability distribution for the number of inflationary e-folds and the amplitude of density fluctuations Q, assuming that the low-energy landscape is described by a random Gaussian potential with a correlation length much smaller than M pl. We find that the distribution for Q has a unique shape and a preferred domain, which depends on the parameters of the low-energy landscape. We discuss some observational implications of this distribution and the constraints it imposes on the landscape parameters.

  5. Energy forest cultivation and the landscape

    International Nuclear Information System (INIS)

    Bell, Simon

    1994-01-01

    The place of energy forestry in the landscape is discussed, principally with reference to Britain and Europe. The importance of design as a means of ensuring an attractive appearance, while meeting functional and economic requirements, is stressed. Simple design principles which help energy forests, mainly short rotation arable coppice, to fit into the landscape are suggested. (author)

  6. Sustainable energy landscapes : designing, planning, and development

    NARCIS (Netherlands)

    Stremke, S.; Dobbelsteen, van den A.

    2013-01-01

    In the near future the appearance and spatial organization of urban and rural landscapes will be strongly influenced by the generation of renewable energy. One of the critical tasks will be the re-integration of these sustainable energy landscapes into the existing environment—which people value and

  7. Experimental Rugged Fitness Landscape in Protein Sequence Space

    OpenAIRE

    HAYASHI, Yuuki; 相田, 拓洋; TOYOTA, Hitoshi; 伏見, 譲; URABE, Itaru; YOMO, Tetsuya

    2006-01-01

    The fitness landscape in sequence space determines the process of biomolecular evolution. To plot the fitness landscape of protein function, we carried out in vitro molecular evolution beginning with a defective fd phage carrying a random polypeptide of 139 amino acids in place of the g3p minor coat protein D2 domain, which is essential for phage infection. After 20 cycles of random substitution at sites 12-130 of the initial random polypeptide and selection for infectivity, the selected phag...

  8. Learning free energy landscapes using artificial neural networks.

    Science.gov (United States)

    Sidky, Hythem; Whitmer, Jonathan K

    2018-03-14

    Existing adaptive bias techniques, which seek to estimate free energies and physical properties from molecular simulations, are limited by their reliance on fixed kernels or basis sets which hinder their ability to efficiently conform to varied free energy landscapes. Further, user-specified parameters are in general non-intuitive yet significantly affect the convergence rate and accuracy of the free energy estimate. Here we propose a novel method, wherein artificial neural networks (ANNs) are used to develop an adaptive biasing potential which learns free energy landscapes. We demonstrate that this method is capable of rapidly adapting to complex free energy landscapes and is not prone to boundary or oscillation problems. The method is made robust to hyperparameters and overfitting through Bayesian regularization which penalizes network weights and auto-regulates the number of effective parameters in the network. ANN sampling represents a promising innovative approach which can resolve complex free energy landscapes in less time than conventional approaches while requiring minimal user input.

  9. Learning free energy landscapes using artificial neural networks

    Science.gov (United States)

    Sidky, Hythem; Whitmer, Jonathan K.

    2018-03-01

    Existing adaptive bias techniques, which seek to estimate free energies and physical properties from molecular simulations, are limited by their reliance on fixed kernels or basis sets which hinder their ability to efficiently conform to varied free energy landscapes. Further, user-specified parameters are in general non-intuitive yet significantly affect the convergence rate and accuracy of the free energy estimate. Here we propose a novel method, wherein artificial neural networks (ANNs) are used to develop an adaptive biasing potential which learns free energy landscapes. We demonstrate that this method is capable of rapidly adapting to complex free energy landscapes and is not prone to boundary or oscillation problems. The method is made robust to hyperparameters and overfitting through Bayesian regularization which penalizes network weights and auto-regulates the number of effective parameters in the network. ANN sampling represents a promising innovative approach which can resolve complex free energy landscapes in less time than conventional approaches while requiring minimal user input.

  10. New interaction paths in the energy landscape: the role of local energy initiatives

    NARCIS (Netherlands)

    de Boer, Jessica; Zuidema, Christian; Gugerell, Katharina

    2018-01-01

    Energy transition is an encompassing process which not only involves the energy system but also the landscape in which the energy system is embedded. Renewable energy is triggering new interactions with local landscapes in physical, socio-economic and institutional senses. We capture these

  11. Energy-landscape Nexus: Advancing a conceptual framework for the design of sustainable energy landscapes

    NARCIS (Netherlands)

    Stremke, S.

    2013-01-01

    For some time now, the concept of “energy landscape” is discussed in academia while more and more practising landscape architects contribute to the siting, designing, and assessment of renewable energy technologies (see Stremke et al. 2012). Yet, there remains some ambiguity what exactly is meant

  12. Mitigation/Adaptation: landscape architecture meets sustainable energy transition

    NARCIS (Netherlands)

    Stremke, S.

    2009-01-01

    Mitigation of climate change and adaptation to renewable energy sources are among the emerging fields of activity in landscape architecture. If landscape architects recognize the need for sustainable development on the basis of renewable energy sources, then how can we contribute to sustainable and

  13. Random versus Deterministic Descent in RNA Energy Landscape Analysis

    Directory of Open Access Journals (Sweden)

    Luke Day

    2016-01-01

    Full Text Available Identifying sets of metastable conformations is a major research topic in RNA energy landscape analysis, and recently several methods have been proposed for finding local minima in landscapes spawned by RNA secondary structures. An important and time-critical component of such methods is steepest, or gradient, descent in attraction basins of local minima. We analyse the speed-up achievable by randomised descent in attraction basins in the context of large sample sets where the size has an order of magnitude in the region of ~106. While the gain for each individual sample might be marginal, the overall run-time improvement can be significant. Moreover, for the two nongradient methods we analysed for partial energy landscapes induced by ten different RNA sequences, we obtained that the number of observed local minima is on average larger by 7.3% and 3.5%, respectively. The run-time improvement is approximately 16.6% and 6.8% on average over the ten partial energy landscapes. For the large sample size we selected for descent procedures, the coverage of local minima is very high up to energy values of the region where the samples were randomly selected from the partial energy landscapes; that is, the difference to the total set of local minima is mainly due to the upper area of the energy landscapes.

  14. Experimental Rugged Fitness Landscape in Protein Sequence Space

    Science.gov (United States)

    Hayashi, Yuuki; Aita, Takuyo; Toyota, Hitoshi; Husimi, Yuzuru; Urabe, Itaru; Yomo, Tetsuya

    2006-01-01

    The fitness landscape in sequence space determines the process of biomolecular evolution. To plot the fitness landscape of protein function, we carried out in vitro molecular evolution beginning with a defective fd phage carrying a random polypeptide of 139 amino acids in place of the g3p minor coat protein D2 domain, which is essential for phage infection. After 20 cycles of random substitution at sites 12–130 of the initial random polypeptide and selection for infectivity, the selected phage showed a 1.7×104-fold increase in infectivity, defined as the number of infected cells per ml of phage suspension. Fitness was defined as the logarithm of infectivity, and we analyzed (1) the dependence of stationary fitness on library size, which increased gradually, and (2) the time course of changes in fitness in transitional phases, based on an original theory regarding the evolutionary dynamics in Kauffman's n-k fitness landscape model. In the landscape model, single mutations at single sites among n sites affect the contribution of k other sites to fitness. Based on the results of these analyses, k was estimated to be 18–24. According to the estimated parameters, the landscape was plotted as a smooth surface up to a relative fitness of 0.4 of the global peak, whereas the landscape had a highly rugged surface with many local peaks above this relative fitness value. Based on the landscapes of these two different surfaces, it appears possible for adaptive walks with only random substitutions to climb with relative ease up to the middle region of the fitness landscape from any primordial or random sequence, whereas an enormous range of sequence diversity is required to climb further up the rugged surface above the middle region. PMID:17183728

  15. Experimental rugged fitness landscape in protein sequence space.

    Science.gov (United States)

    Hayashi, Yuuki; Aita, Takuyo; Toyota, Hitoshi; Husimi, Yuzuru; Urabe, Itaru; Yomo, Tetsuya

    2006-12-20

    The fitness landscape in sequence space determines the process of biomolecular evolution. To plot the fitness landscape of protein function, we carried out in vitro molecular evolution beginning with a defective fd phage carrying a random polypeptide of 139 amino acids in place of the g3p minor coat protein D2 domain, which is essential for phage infection. After 20 cycles of random substitution at sites 12-130 of the initial random polypeptide and selection for infectivity, the selected phage showed a 1.7x10(4)-fold increase in infectivity, defined as the number of infected cells per ml of phage suspension. Fitness was defined as the logarithm of infectivity, and we analyzed (1) the dependence of stationary fitness on library size, which increased gradually, and (2) the time course of changes in fitness in transitional phases, based on an original theory regarding the evolutionary dynamics in Kauffman's n-k fitness landscape model. In the landscape model, single mutations at single sites among n sites affect the contribution of k other sites to fitness. Based on the results of these analyses, k was estimated to be 18-24. According to the estimated parameters, the landscape was plotted as a smooth surface up to a relative fitness of 0.4 of the global peak, whereas the landscape had a highly rugged surface with many local peaks above this relative fitness value. Based on the landscapes of these two different surfaces, it appears possible for adaptive walks with only random substitutions to climb with relative ease up to the middle region of the fitness landscape from any primordial or random sequence, whereas an enormous range of sequence diversity is required to climb further up the rugged surface above the middle region.

  16. Experimental rugged fitness landscape in protein sequence space.

    Directory of Open Access Journals (Sweden)

    Yuuki Hayashi

    Full Text Available The fitness landscape in sequence space determines the process of biomolecular evolution. To plot the fitness landscape of protein function, we carried out in vitro molecular evolution beginning with a defective fd phage carrying a random polypeptide of 139 amino acids in place of the g3p minor coat protein D2 domain, which is essential for phage infection. After 20 cycles of random substitution at sites 12-130 of the initial random polypeptide and selection for infectivity, the selected phage showed a 1.7x10(4-fold increase in infectivity, defined as the number of infected cells per ml of phage suspension. Fitness was defined as the logarithm of infectivity, and we analyzed (1 the dependence of stationary fitness on library size, which increased gradually, and (2 the time course of changes in fitness in transitional phases, based on an original theory regarding the evolutionary dynamics in Kauffman's n-k fitness landscape model. In the landscape model, single mutations at single sites among n sites affect the contribution of k other sites to fitness. Based on the results of these analyses, k was estimated to be 18-24. According to the estimated parameters, the landscape was plotted as a smooth surface up to a relative fitness of 0.4 of the global peak, whereas the landscape had a highly rugged surface with many local peaks above this relative fitness value. Based on the landscapes of these two different surfaces, it appears possible for adaptive walks with only random substitutions to climb with relative ease up to the middle region of the fitness landscape from any primordial or random sequence, whereas an enormous range of sequence diversity is required to climb further up the rugged surface above the middle region.

  17. Potential energy landscape of TIP4P/2005 water

    Science.gov (United States)

    Handle, Philip H.; Sciortino, Francesco

    2018-04-01

    We report a numerical study of the statistical properties of the potential energy landscape of TIP4P/2005, one of the most accurate rigid water models. We show that, in the region where equilibrated configurations can be generated, a Gaussian landscape description is able to properly describe the model properties. We also find that the volume dependence of the landscape properties is consistent with the existence of a locus of density maxima in the phase diagram. The landscape-based equation of state accurately reproduces the TIP4P/2005 pressure-vs-volume curves, providing a sound extrapolation of the free-energy at low T. A positive-pressure liquid-liquid critical point is predicted by the resulting free-energy.

  18. Characterizing structural transitions using localized free energy landscape analysis.

    Directory of Open Access Journals (Sweden)

    Nilesh K Banavali

    Full Text Available Structural changes in molecules are frequently observed during biological processes like replication, transcription and translation. These structural changes can usually be traced to specific distortions in the backbones of the macromolecules involved. Quantitative energetic characterization of such distortions can greatly advance the atomic-level understanding of the dynamic character of these biological processes.Molecular dynamics simulations combined with a variation of the Weighted Histogram Analysis Method for potential of mean force determination are applied to characterize localized structural changes for the test case of cytosine (underlined base flipping in a GTCAGCGCATGG DNA duplex. Free energy landscapes for backbone torsion and sugar pucker degrees of freedom in the DNA are used to understand their behavior in response to the base flipping perturbation. By simplifying the base flipping structural change into a two-state model, a free energy difference of upto 14 kcal/mol can be attributed to the flipped state relative to the stacked Watson-Crick base paired state. This two-state classification allows precise evaluation of the effect of base flipping on local backbone degrees of freedom.The calculated free energy landscapes of individual backbone and sugar degrees of freedom expectedly show the greatest change in the vicinity of the flipping base itself, but specific delocalized effects can be discerned upto four nucleotide positions away in both 5' and 3' directions. Free energy landscape analysis thus provides a quantitative method to pinpoint the determinants of structural change on the atomic scale and also delineate the extent of propagation of the perturbation along the molecule. In addition to nucleic acids, this methodology is anticipated to be useful for studying conformational changes in all macromolecules, including carbohydrates, lipids, and proteins.

  19. Probing the Free Energy Landscape of the FBP28 WW Domain Using Multiple Techniques

    NARCIS (Netherlands)

    Periole, Xavier; Allen, Lucy R.; Tamiola, Kamil; Mark, Alan E.; Paci, Emanuele

    The free-energy landscape of a small protein, the FBP 28 WW domain, has been explored using molecular dynamics (MD) simulations with alternative descriptions of the molecule. The molecular models used range from coarse-grained to all-atom with either an implicit or explicit treatment of the solvent.

  20. Free-energy landscape of a hyperstable RNA tetraloop.

    Science.gov (United States)

    Miner, Jacob C; Chen, Alan A; García, Angel E

    2016-06-14

    We report the characterization of the energy landscape and the folding/unfolding thermodynamics of a hyperstable RNA tetraloop obtained through high-performance molecular dynamics simulations at microsecond timescales. Sampling of the configurational landscape is conducted using temperature replica exchange molecular dynamics over three isochores at high, ambient, and negative pressures to determine the thermodynamic stability and the free-energy landscape of the tetraloop. The simulations reveal reversible folding/unfolding transitions of the tetraloop into the canonical A-RNA conformation and the presence of two alternative configurations, including a left-handed Z-RNA conformation and a compact purine Triplet. Increasing hydrostatic pressure shows a stabilizing effect on the A-RNA conformation and a destabilization of the left-handed Z-RNA. Our results provide a comprehensive description of the folded free-energy landscape of a hyperstable RNA tetraloop and highlight the significant advances of all-atom molecular dynamics in describing the unbiased folding of a simple RNA secondary structure motif.

  1. Frustration in the energy landscapes of multidomain protein misfolding.

    Science.gov (United States)

    Zheng, Weihua; Schafer, Nicholas P; Wolynes, Peter G

    2013-01-29

    Frustration from strong interdomain interactions can make misfolding a more severe problem in multidomain proteins than in single-domain proteins. On the basis of bioinformatic surveys, it has been suggested that lowering the sequence identity between neighboring domains is one of nature's solutions to the multidomain misfolding problem. We investigate folding of multidomain proteins using the associative-memory, water-mediated, structure and energy model (AWSEM), a predictive coarse-grained protein force field. We find that reducing sequence identity not only decreases the formation of domain-swapped contacts but also decreases the formation of strong self-recognition contacts between β-strands with high hydrophobic content. The ensembles of misfolded structures that result from forming these amyloid-like interactions are energetically disfavored compared with the native state, but entropically favored. Therefore, these ensembles are more stable than the native ensemble under denaturing conditions, such as high temperature. Domain-swapped contacts compete with self-recognition contacts in forming various trapped states, and point mutations can shift the balance between the two types of interaction. We predict that multidomain proteins that lack these specific strong interdomain interactions should fold reliably.

  2. Evaluating the landscape impact of renewable energy plants

    Science.gov (United States)

    Ioannidis, Romanos; Koutsoyiannis, Demetris

    2017-04-01

    Different types of renewable energy have been on an ongoing competition with each other. There has been a lot of research comparing the most common types of renewable energy plants in relation with their efficiency, cost and environmental impact. However, few papers so far have attempted to analyse their impact on landscape and there has never been in depth research on which type of renewable energy causes the least impact on the natural, cultural and aesthetic characteristics of a landscape. This seems to be a significant omission given the vast areas of land already covered with renewable energy plants and the worldwide plans for many more renewable energy projects in the future. Meanwhile, the low aesthetic quality of renewable energy plants has already been an obstacle to their further development, with several relevant examples from countries such as Spain and the Netherlands. There have even been cases where aesthetic degradation is the primary or even the single argument of the opposition to proposed plants. In any case, the aesthetic design and the integration of renewable energy plants into the landscape should really be important design parameters if we plan those projects to truly be sustainable and to be considered complete works of engineering. To initiate dialogue over those aspects of renewable energy, we provide a first comparison on hydro, solar and wind energy. To materialize this comparison, we use data from existing dams, photovoltaic and wind farms. Initially, the average area per MW covered by each type of energy plant is calculated and then evaluated qualitatively from a landscape-impact perspective. Although the area affected is comparable in these three cases, the analysis of the data suggests that dams offer a considerable amount of advantages compared to the other two types of plants. This conclusion arises from the fact that dams, whose basic impact to the landscape is the creation of an artificial lake, contribute much less to the

  3. Energy Landscapes for the Self-Assembly of Supramolecular Polyhedra

    Science.gov (United States)

    Russell, Emily R.; Menon, Govind

    2016-06-01

    We develop a mathematical model for the energy landscape of polyhedral supramolecular cages recently synthesized by self-assembly (Sun et al. in Science 328:1144-1147, 2010). Our model includes two essential features of the experiment: (1) geometry of the organic ligands and metallic ions; and (2) combinatorics. The molecular geometry is used to introduce an energy that favors square-planar vertices (modeling {Pd}^{2+} ions) and bent edges with one of two preferred opening angles (modeling boomerang-shaped ligands of two types). The combinatorics of the model involve two-colorings of edges of polyhedra with four-valent vertices. The set of such two-colorings, quotiented by the octahedral symmetry group, has a natural graph structure and is called the combinatorial configuration space. The energy landscape of our model is the energy of each state in the combinatorial configuration space. The challenge in the computation of the energy landscape is a combinatorial explosion in the number of two-colorings of edges. We describe sampling methods based on the symmetries of the configurations and connectivity of the configuration graph. When the two preferred opening angles encompass the geometrically ideal angle, the energy landscape exhibits a very low-energy minimum for the most symmetric configuration at equal mixing of the two angles, even when the average opening angle does not match the ideal angle.

  4. The effects of landscaping on the residential cooling energy

    Science.gov (United States)

    Misni, A.

    2018-02-01

    This paper examines the effectiveness of landscaping on the air-conditioning energy saving of houses in a tropical environment. This case study involved looking at the construction and landscaping of three single-family houses in three sections of Shah Alam, Selangor, Malaysia. The houses ranged in age from 5 to 30 years old, which provided different examples of construction and maturity levels of the surrounding landscaping. Landscaping affects the thermal performance as well as on the air-conditioning energy of houses, in how it provides shade, channels wind, and evapotranspiration. While the construction of the three houses was similar, they were different in size and design, including their landscape design. These houses were chosen because they are representative of single-family tropical houses and landscaping styles in Malaysia since 30 years ago. Three houses were chosen; the 30-year-old house, the 10-year-old house, and the 5-year-old house. In a tropical country, landscaping is used to reduce the effects of the hot and humid climate. The houses spent 15-45% of the electricity cost on cooling. These results were influenced by human factors and the surrounding landscaping. Every type of vegetation, such as trees, grass, shrubs, groundcover, and turf, contributes to reducing air temperatures near the house and providing evaporative cooling.

  5. Potential energy landscapes of elemental and heterogeneous chalcogen clusters

    International Nuclear Information System (INIS)

    Mauro, John C.; Loucks, Roger J.; Balakrishnan, Jitendra; Varshneya, Arun K.

    2006-01-01

    We describe the potential energy landscapes of elemental S 8 , Se 8 , and Te 8 clusters using disconnectivity graphs. Inherent structures include both ring and chain configurations, with rings especially dominant in Se 8 . We also map the potential energy landscapes of heterogeneous Se n (S,Te) 8-n clusters, which offer insights into the structure of heterogeneous chalcogen glasses

  6. Energy Transition: Missed Opportunities and Emerging Challenges for Landscape Planning and Designing

    Directory of Open Access Journals (Sweden)

    Renée M. de Waal

    2014-07-01

    Full Text Available Making the shift from fossil fuels to renewable energy seems inevitable. Because energy transition poses new challenges and opportunities to the discipline of landscape architecture, the questions addressed in this paper are: (1 what landscape architects can learn from successful energy transitions in Güssing, Jühnde and Samsø; and (2 to what extent landscape architecture (or other spatial disciplines contributed to energy transition in the aforementioned cases. An exploratory, comparative case study was conducted to identify differences and similarities among the cases, to answer the research questions, and to formulate recommendations for further research and practice. The comparison indicated that the realized renewable energy systems are context-dependent and, therefore, specifically designed to meet the respective energy demand, making use of the available potentials for renewable energy generation and efficiency. Further success factors seemed to be the presence of (local frontrunners and a certain degree of citizen participation. The relatively smooth implementation of renewable energy technologies in Jühnde and on Samsø may indicate the importance of careful and (partly institutionalized consideration of landscape impact, siting and design. Comparing the cases against the literature demonstrated that landscape architects were not as involved as they, theoretically, could have been. However, particularly when the aim is sustainable development, rather than “merely” renewable energy provision, the integrative concept of “sustainable energy landscapes” can be the arena where landscape architecture and other disciplines meet to pursue global sustainability goals, while empowering local communities and safeguarding landscape quality.

  7. Energy landscapes of resting-state brain networks

    Directory of Open Access Journals (Sweden)

    Takamitsu eWatanabe

    2014-02-01

    Full Text Available During rest, the human brain performs essential functions such as memory maintenance, which are associated with resting-state brain networks (RSNs including the default-mode network (DMN and frontoparietal network (FPN. Previous studies based on spiking-neuron network models and their reduced models, as well as those based on imaging data, suggest that resting-state network activity can be captured as attractor dynamics, i.e., dynamics of the brain state toward an attractive state and transitions between different attractors. Here, we analyze the energy landscapes of the RSNs by applying the maximum entropy model, or equivalently the Ising spin model, to human RSN data. We use the previously estimated parameter values to define the energy landscape, and the disconnectivity graph method to estimate the number of local energy minima (equivalent to attractors in attractor dynamics, the basin size, and hierarchical relationships among the different local minima. In both of the DMN and FPN, low-energy local minima tended to have large basins. A majority of the network states belonged to a basin of one of a few local minima. Therefore, a small number of local minima constituted the backbone of each RSN. In the DMN, the energy landscape consisted of two groups of low-energy local minima that are separated by a relatively high energy barrier. Within each group, the activity patterns of the local minima were similar, and different minima were connected by relatively low energy barriers. In the FPN, all dominant energy were separated by relatively low energy barriers such that they formed a single coarse-grained global minimum. Our results indicate that multistable attractor dynamics may underlie the DMN, but not the FPN, and assist memory maintenance with different memory states.

  8. Ideal glass transitions in thin films: An energy landscape perspective

    Science.gov (United States)

    Truskett, Thomas M.; Ganesan, Venkat

    2003-07-01

    We introduce a mean-field model for the potential energy landscape of a thin fluid film confined between parallel substrates. The model predicts how the number of accessible basins on the energy landscape and, consequently, the film's ideal glass transition temperature depend on bulk pressure, film thickness, and the strength of the fluid-fluid and fluid-substrate interactions. The predictions are in qualitative agreement with the experimental trends for the kinetic glass transition temperature of thin films, suggesting the utility of landscape-based approaches for studying the behavior of confined fluids.

  9. How animals distribute themselves in space: variable energy landscapes

    OpenAIRE

    Masello, Juan F.; Kato, Akiko; Sommerfeld, Julia; Mattern, Thomas; Quillfeldt, Petra

    2017-01-01

    Background Foraging efficiency determines whether animals will be able to raise healthy broods, maintain their own condition, avoid predators and ultimately increase their fitness. Using accelerometers and GPS loggers, features of the habitat and the way animals deal with variable conditions can be translated into energetic costs of movement, which, in turn, can be translated to energy landscapes.We investigated energy landscapes in Gentoo Penguins Pygoscelis papua from two colonies at New Is...

  10. Hierarchical structure of the energy landscape of proteins revisited by time series analysis. II. Investigation of explicit solvent effects

    Science.gov (United States)

    Alakent, Burak; Camurdan, Mehmet C.; Doruker, Pemra

    2005-10-01

    Time series analysis tools are employed on the principal modes obtained from the Cα trajectories from two independent molecular-dynamics simulations of α-amylase inhibitor (tendamistat). Fluctuations inside an energy minimum (intraminimum motions), transitions between minima (interminimum motions), and relaxations in different hierarchical energy levels are investigated and compared with those encountered in vacuum by using different sampling window sizes and intervals. The low-frequency low-indexed mode relationship, established in vacuum, is also encountered in water, which shows the reliability of the important dynamics information offered by principal components analysis in water. It has been shown that examining a short data collection period (100ps) may result in a high population of overdamped modes, while some of the low-frequency oscillations (memory: future conformations are less dependent on previous conformations due to the lowering of energy barriers in hierarchical levels of the energy landscape. In short-time dynamics (sight contradicts. However, this comes about because water enhances the transitions between minima and forces the protein to reduce its already inherent inability to maintain oscillations observed in vacuum. Some of the frequencies lower than 10cm-1 are found to be overdamped, while those higher than 20cm-1 are slightly increased. As for the long-time dynamics in water, it is found that random-walk motion is maintained for approximately 200ps (about five times of that in vacuum) in the low-indexed modes, showing the lowering of energy barriers between the higher-level minima.

  11. Membranes: A Variety of Energy Landscapes for Many Transfer Opportunities.

    Science.gov (United States)

    Bacchin, Patrice

    2018-02-22

    A membrane can be represented by an energy landscape that solutes or colloids must cross. A model accounting for the momentum and the mass balances in the membrane energy landscape establishes a new way of writing for the Darcy law. The counter-pressure in the Darcy law is no longer written as the result of an osmotic pressure difference but rather as a function of colloid-membrane interactions. The ability of the model to describe the physics of the filtration is discussed in detail. This model is solved in a simplified energy landscape to derive analytical relationships that describe the selectivity and the counter-pressure from ab initio operating conditions. The model shows that the stiffness of the energy landscape has an impact on the process efficiency: a gradual increase in interactions (such as with hourglass pore shape) can reduce the separation energetic cost. It allows the introduction of a new paradigm to increase membrane efficiency: the accumulation that is inherent to the separation must be distributed across the membrane. Asymmetric interactions thus lead to direction-dependent transfer properties and the membrane exhibits diode behavior. These new transfer opportunities are discussed.

  12. Integrated visions (part II): Envisioning Sustainable Energy Landscapes

    NARCIS (Netherlands)

    Stremke, S.; Koh, J.; Neven, C.T.; Boekel, A.

    2012-01-01

    ABSTRACT Climate change and resource depletion are driving the transition to renewable energy sources. Both the supply of renewables and the demand for energy are influenced by the physical environment and therefore concern spatial planning and landscape design. Envisioning the longterm development

  13. Energy transition: towards landscape devastation?

    International Nuclear Information System (INIS)

    Posokhow, Andre

    2013-09-01

    The author criticizes some aspects of the content of the French policy for energy transition. He states that the objective of reduction of greenhouse emissions is unreachable and moreover useless when China keeps on opening new coal-fired power stations. He states that temperatures do not increase any longer and that it is not sure that CO 2 emissions are responsible for past increases. He outlines that the power of wind turbines is only a quarter of their theoretical one, that replacing nuclear energy by wind energy would require the installation of 33.000 wind turbines. He states that objectives of energy saving are not credible, and that the energy mix predictions are fuzzy. He outlines contradictions about the nuclear power station life duration, states that the installation of 210 wind turbines per district would devastate the French landscape

  14. Conference on landscape impacts of wind energy and local acceptance: France-Germany crossed views

    International Nuclear Information System (INIS)

    Bouscatel, Jerome; Olagne, Regis; Derkenne, Chantal; Galiano, Mila; Mayer, Joerg; Ratzbor, Guenter; Laborgne, Pia; Nadai, Alain; Ratouis, Marie-Odile; Schoebel-Rutschmann, Soeren; Petit, Jean-Francois; Guennewig, Dieter; Portales, David

    2008-01-01

    The French-German office for Renewable energies (OFAEnR) organised a conference on the landscape impacts of wind energy. In the framework of this French-German exchange of experience, more than 100 participants exchanged views on the environmental impact of wind farms and the opinion of residents. This document brings together the available presentations (slides) made during this event: 1 - French people and wind energy (Mila Galiano); 2 - Wind energy acceptance in Germany: an essential factor for the wind industry development (Joerg Mayer); 3 - Taking into account landscapes and residents in the development of wind farms: a France-Germany comparison (Pia Laborgne, Alain Nadai); 3 - Wind energy development supervision thanks to territorial planning in Germany (Guenter Ratzbor); 4 - Landscape challenges in wind energy development: point of view and role of a state decentralised department (Marie-Odile Ratouis); 5 - Park or landscape - Wind turbines as elements of the cultural landscape (Soeren Schoebel-Rutschmann); 6 - How should a developer approach the 'landscape' aspect when foreseeing a wind energy project installation (Jean-Francois Petit); 7 - More consensual wind energy projects along highways, railways and overhead power lines? (Dieter Guennewig); 8 - The 'wings top': un example of participatory and citizen's project (David Portales)

  15. Ideal glass transitions in thin films: An energy landscape perspective

    OpenAIRE

    Truskett, Thomas M.; Ganesan, Venkat

    2003-01-01

    We introduce a mean-field model for the potential energy landscape of a thin fluid film confined between parallel substrates. The model predicts how the number of accessible basins on the energy landscape and, consequently, the film's ideal glass transition temperature depend on bulk pressure, film thickness, and the strength of the fluid-fluid and fluid-substrate interactions. The predictions are in qualitative agreement with the experimental trends for the kinetic glass transition temperatu...

  16. Quantifying the topography of the intrinsic energy landscape of flexible biomolecular recognition

    Science.gov (United States)

    Chu, Xiakun; Gan, Linfeng; Wang, Erkang; Wang, Jin

    2013-01-01

    Biomolecular functions are determined by their interactions with other molecules. Biomolecular recognition is often flexible and associated with large conformational changes involving both binding and folding. However, the global and physical understanding for the process is still challenging. Here, we quantified the intrinsic energy landscapes of flexible biomolecular recognition in terms of binding–folding dynamics for 15 homodimers by exploring the underlying density of states, using a structure-based model both with and without considering energetic roughness. By quantifying three individual effective intrinsic energy landscapes (one for interfacial binding, two for monomeric folding), the association mechanisms for flexible recognition of 15 homodimers can be classified into two-state cooperative “coupled binding–folding” and three-state noncooperative “folding prior to binding” scenarios. We found that the association mechanism of flexible biomolecular recognition relies on the interplay between the underlying effective intrinsic binding and folding energy landscapes. By quantifying the whole global intrinsic binding–folding energy landscapes, we found strong correlations between the landscape topography measure Λ (dimensionless ratio of energy gap versus roughness modulated by the configurational entropy) and the ratio of the thermodynamic stable temperature versus trapping temperature, as well as between Λ and binding kinetics. Therefore, the global energy landscape topography determines the binding–folding thermodynamics and kinetics, crucial for the feasibility and efficiency of realizing biomolecular function. We also found “U-shape” temperature-dependent kinetic behavior and a dynamical cross-over temperature for dividing exponential and nonexponential kinetics for two-state homodimers. Our study provides a unique way to bridge the gap between theory and experiments. PMID:23754431

  17. Quantum mechanical electronic structure calculation reveals orientation dependence of hydrogen bond energy in proteins.

    Science.gov (United States)

    Mondal, Abhisek; Datta, Saumen

    2017-06-01

    Hydrogen bond plays a unique role in governing macromolecular interactions with exquisite specificity. These interactions govern the fundamental biological processes like protein folding, enzymatic catalysis, molecular recognition. Despite extensive research work, till date there is no proper report available about the hydrogen bond's energy surface with respect to its geometric parameters, directly derived from proteins. Herein, we have deciphered the potential energy landscape of hydrogen bond directly from the macromolecular coordinates obtained from Protein Data Bank using quantum mechanical electronic structure calculations. The findings unravel the hydrogen bonding energies of proteins in parametric space. These data can be used to understand the energies of such directional interactions involved in biological molecules. Quantitative characterization has also been performed using Shannon entropic calculations for atoms participating in hydrogen bond. Collectively, our results constitute an improved way of understanding hydrogen bond energies in case of proteins and complement the knowledge-based potential. Proteins 2017; 85:1046-1055. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. The relative importance of physical and biological energy in landscape evolution

    Science.gov (United States)

    Turowski, J. M.; Schwanghart, W.

    2017-12-01

    Landscapes are formed by the interplay of uplift and geomorphic processes, including interacting and competing physical and biological processes. For example, roots re-inforce soil and thereby stabilize hillslopes and the canopy cover of the forest may mediate the impact of precipitation. Furthermore, plants and animals act as geomorphic agents, directly altering landscape response and dynamics by their actions: tree roots may crack rocks, thus changing subsurface water flows and exposing fresh material for denudation; fungi excrete acids that accelerate rates of chemical weathering, and burrowing animals displace soil and rocks while digging holes for shelter or in search of food. Energetically, landscapes can be viewed as open systems in which topography stores potential energy above a base level. Tectonic processes add energy to the system by uplift and mechanically altering rock properties. Especially in unvegetated regions, erosion and transport by wind can be an important geomorphic process. Advection of atmospheric moisture in high altitudes provides potential energy that is converted by water fluxes through catchments. At the same time, the conversion of solar energy through atmospheric and biological processes drives primary production of living organisms. If we accept that biota influence geomorphic processes, then what is their energetic contribution to landscape evolution relative to physical processes? Using two case studies, we demonstrate that all components of energy input are negligible apart from biological production, quantified by net primary productivity (NPP) and potential energy conversion by water that is placed high up in the landscape as rainfall and leaves it as runoff. Assuming that the former is representative for biological energy and the latter for physical energy, we propose that the ratio of these two values can be used as a proxy for the relative importance of biological and physical processes in landscape evolution. All necessary

  19. Recent developments in the theory of protein folding: searching for the global energy minimum.

    Science.gov (United States)

    Scheraga, H A

    1996-04-16

    Statistical mechanical theories and computer simulation are being used to gain an understanding of the fundamental features of protein folding. A major obstacle in the computation of protein structures is the multiple-minima problem arising from the existence of many local minima in the multidimensional energy landscape of the protein. This problem has been surmounted for small open-chain and cyclic peptides, and for regular-repeating sequences of models of fibrous proteins. Progress is being made in resolving this problem for globular proteins.

  20. The changing geopolitical landscape of energy

    International Nuclear Information System (INIS)

    Lesourne, Jacques

    2011-08-01

    The author first discusses the impact of the financial crisis of 2008, and of the large-scale exploitation of shale gases in the USA on energy policies and on the geopolitical landscape of energy. Then, he discusses the influence that events which occurred in 2011 had on these issues: firstly, the Copenhagen and Cancun Conferences, secondly, the Fukushima accident, thirdly, the nuclear phasing-out by Germany and incidentally by Italy, and fourthly, the Arab Spring. In the next parts, he comments the consequences for the European energy policy, and the perspectives for the struggle against climate change

  1. Free energy landscape of a minimalist salt bridge model.

    Science.gov (United States)

    Li, Xubin; Lv, Chao; Corbett, Karen M; Zheng, Lianqing; Wu, Dongsheng; Yang, Wei

    2016-01-01

    Salt bridges are essential to protein stability and dynamics. Despite the importance, there has been scarce of detailed discussion on how salt bridge partners interact with each other in distinct solvent exposed environments. In this study, employing a recent generalized orthogonal space tempering (gOST) method, we enabled efficient molecular dynamics simulation of repetitive breaking and reforming of salt bridge structures within a minimalist salt-bridge model, the Asp-Arg dipeptide and thereby were able to map its detailed free energy landscape in aqueous solution. Free energy surface analysis shows that although individually-solvated states are more favorable, salt-bridge states still occupy a noticeable portion of the overall population. Notably, the competing forces, e.g. intercharge attractions that drive the formation of salt bridges and solvation forces that pull the charged groups away from each other, are energetically comparable. As the result, the salt bridge stability is highly tunable by local environments; for instance when local water molecules are perturbed to interact more strongly with each other, the population of the salt-bridge states is likely to increase. Our results reveal the critical role of local solvent structures in modulating salt-bridge partner interactions and imply the importance of water fluctuations on conformational dynamics that involves solvent accessible salt bridge formations. © 2015 The Protein Society.

  2. Technology assessment in energy landscapes. Agent-based modeling of energy conflicts

    International Nuclear Information System (INIS)

    Scheffran, Juergen; Link, P. Michael; Shaaban, Mostafa; Suesser, Diana

    2017-01-01

    The risks and conflicts of the fossil-nuclear age are in contrast to the effects of renewable energies which appear in a largely positive light. However, the transformation towards a low-carbon energy supply creates new energy landscapes with a high demand for suitable land areas - which may also provoke energy conflicts. Technology assessment can contribute to reducing such energy conflicts and increasing public acceptance by using spatial agent-based models that represent dynamic decisions and interactions of stakeholders regarding energy alternatives and land-use options. Northern Germany serves as a case study region where farmers and communities are local actors of the energy transition.

  3. Numerical evaluation of the statistical properties of a potential energy landscape

    International Nuclear Information System (INIS)

    Nave, E La; Sciortino, F; Tartaglia, P; Michele, C De; Mossa, S

    2003-01-01

    The techniques which allow the numerical evaluation of the statistical properties of the potential energy landscape for models of simple liquids are reviewed and critically discussed. Expressions for the liquid free energy and its vibrational and configurational components are reported. Finally, a possible model for the statistical properties of the landscape, which appears to describe correctly fragile liquids in the region where equilibrium simulations are feasible, is discussed

  4. Decipher the mechanisms of protein conformational changes induced by nucleotide binding through free-energy landscape analysis: ATP binding to Hsp70.

    Directory of Open Access Journals (Sweden)

    Adrien Nicolaï

    Full Text Available ATP regulates the function of many proteins in the cell by transducing its binding and hydrolysis energies into protein conformational changes by mechanisms which are challenging to identify at the atomic scale. Based on molecular dynamics (MD simulations, a method is proposed to analyze the structural changes induced by ATP binding to a protein by computing the effective free-energy landscape (FEL of a subset of its coordinates along its amino-acid sequence. The method is applied to characterize the mechanism by which the binding of ATP to the nucleotide-binding domain (NBD of Hsp70 propagates a signal to its substrate-binding domain (SBD. Unbiased MD simulations were performed for Hsp70-DnaK chaperone in nucleotide-free, ADP-bound and ATP-bound states. The simulations revealed that the SBD does not interact with the NBD for DnaK in its nucleotide-free and ADP-bound states whereas the docking of the SBD was found in the ATP-bound state. The docked state induced by ATP binding found in MD is an intermediate state between the initial nucleotide-free and final ATP-bound states of Hsp70. The analysis of the FEL projected along the amino-acid sequence permitted to identify a subset of 27 protein internal coordinates corresponding to a network of 91 key residues involved in the conformational change induced by ATP binding. Among the 91 residues, 26 are identified for the first time, whereas the others were shown relevant for the allosteric communication of Hsp70 s in several experiments and bioinformatics analysis. The FEL analysis revealed also the origin of the ATP-induced structural modifications of the SBD recently measured by Electron Paramagnetic Resonance. The pathway between the nucleotide-free and the intermediate state of DnaK was extracted by applying principal component analysis to the subset of internal coordinates describing the transition. The methodology proposed is general and could be applied to analyze allosteric communication in

  5. Specificity and affinity quantification of flexible recognition from underlying energy landscape topography.

    Directory of Open Access Journals (Sweden)

    Xiakun Chu

    2014-08-01

    Full Text Available Flexibility in biomolecular recognition is essential and critical for many cellular activities. Flexible recognition often leads to moderate affinity but high specificity, in contradiction with the conventional wisdom that high affinity and high specificity are coupled. Furthermore, quantitative understanding of the role of flexibility in biomolecular recognition is still challenging. Here, we meet the challenge by quantifying the intrinsic biomolecular recognition energy landscapes with and without flexibility through the underlying density of states. We quantified the thermodynamic intrinsic specificity by the topography of the intrinsic binding energy landscape and the kinetic specificity by association rate. We found that the thermodynamic and kinetic specificity are strongly correlated. Furthermore, we found that flexibility decreases binding affinity on one hand, but increases binding specificity on the other hand, and the decreasing or increasing proportion of affinity and specificity are strongly correlated with the degree of flexibility. This shows more (less flexibility leads to weaker (stronger coupling between affinity and specificity. Our work provides a theoretical foundation and quantitative explanation of the previous qualitative studies on the relationship among flexibility, affinity and specificity. In addition, we found that the folding energy landscapes are more funneled with binding, indicating that binding helps folding during the recognition. Finally, we demonstrated that the whole binding-folding energy landscapes can be integrated by the rigid binding and isolated folding energy landscapes under weak flexibility. Our results provide a novel way to quantify the affinity and specificity in flexible biomolecular recognition.

  6. Causality, transfer entropy, and allosteric communication landscapes in proteins with harmonic interactions.

    Science.gov (United States)

    Hacisuleyman, Aysima; Erman, Burak

    2017-06-01

    A fast and approximate method of generating allosteric communication landscapes in proteins is presented by using Schreiber's entropy transfer concept in combination with the Gaussian Network Model of proteins. Predictions of the model and the allosteric communication landscapes generated show that information transfer in proteins does not necessarily take place along a single path, but an ensemble of pathways is possible. The model emphasizes that knowledge of entropy only is not sufficient for determining allosteric communication and additional information based on time delayed correlations should be introduced, which leads to the presence of causality in proteins. The model provides a simple tool for mapping entropy sink-source relations into pairs of residues. By this approach, residues that should be manipulated to control protein activity may be determined. This should be of great importance for allosteric drug design and for understanding the effects of mutations on function. The model is applied to determine allosteric communication in three proteins, Ubiquitin, Pyruvate Kinase, and the PDZ domain. Predictions are in agreement with molecular dynamics simulations and experimental evidence. Proteins 2017; 85:1056-1064. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Conformational landscape of an amyloid intra-cellular domain and Landau-Ginzburg-Wilson paradigm in protein dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Jin; He, Jianfeng, E-mail: Antti.Niemi@physics.uu.se, E-mail: hjf@bit.edu.cn [School of Physics, Beijing Institute of Technology, Beijing 100081 (China); Niemi, Antti J., E-mail: Antti.Niemi@physics.uu.se, E-mail: hjf@bit.edu.cn [School of Physics, Beijing Institute of Technology, Beijing 100081 (China); Department of Physics and Astronomy, Uppsala University, P.O. Box 803, S-75108 Uppsala (Sweden); Laboratoire de Mathematiques et Physique Theorique CNRS UMR 6083, Fédération Denis Poisson, Université de Tours, Parc de Grandmont, F37200 Tours (France)

    2016-07-28

    The Landau-Ginzburg-Wilson paradigm is proposed as a framework, to investigate the conformational landscape of intrinsically unstructured proteins. A universal Cα-trace Landau free energy is deduced from general symmetry considerations, with the ensuing all-atom structure modeled using publicly available reconstruction programs Pulchra and Scwrl. As an example, the conformational stability of an amyloid precursor protein intra-cellular domain (AICD) is inspected; the reference conformation is the crystallographic structure with code 3DXC in Protein Data Bank (PDB) that describes a heterodimer of AICD and a nuclear multi-domain adaptor protein Fe65. Those conformations of AICD that correspond to local or near-local minima of the Landau free energy are identified. For this, the response of the original 3DXC conformation to variations in the ambient temperature is investigated, using the Glauber algorithm. The conclusion is that in isolation the AICD conformation in 3DXC must be unstable. A family of degenerate conformations that minimise the Landau free energy is identified, and it is proposed that the native state of an isolated AICD is a superposition of these conformations. The results are fully in line with the presumed intrinsically unstructured character of isolated AICD and should provide a basis for a systematic analysis of AICD structure in future NMR experiments.

  8. Conformational landscape of an amyloid intra-cellular domain and Landau-Ginzburg-Wilson paradigm in protein dynamics

    International Nuclear Information System (INIS)

    Dai, Jin; He, Jianfeng; Niemi, Antti J.

    2016-01-01

    The Landau-Ginzburg-Wilson paradigm is proposed as a framework, to investigate the conformational landscape of intrinsically unstructured proteins. A universal Cα-trace Landau free energy is deduced from general symmetry considerations, with the ensuing all-atom structure modeled using publicly available reconstruction programs Pulchra and Scwrl. As an example, the conformational stability of an amyloid precursor protein intra-cellular domain (AICD) is inspected; the reference conformation is the crystallographic structure with code 3DXC in Protein Data Bank (PDB) that describes a heterodimer of AICD and a nuclear multi-domain adaptor protein Fe65. Those conformations of AICD that correspond to local or near-local minima of the Landau free energy are identified. For this, the response of the original 3DXC conformation to variations in the ambient temperature is investigated, using the Glauber algorithm. The conclusion is that in isolation the AICD conformation in 3DXC must be unstable. A family of degenerate conformations that minimise the Landau free energy is identified, and it is proposed that the native state of an isolated AICD is a superposition of these conformations. The results are fully in line with the presumed intrinsically unstructured character of isolated AICD and should provide a basis for a systematic analysis of AICD structure in future NMR experiments.

  9. Direct design of an energy landscape with bistable DNA origami mechanisms.

    Science.gov (United States)

    Zhou, Lifeng; Marras, Alexander E; Su, Hai-Jun; Castro, Carlos E

    2015-03-11

    Structural DNA nanotechnology provides a feasible technique for the design and fabrication of complex geometries even exhibiting controllable dynamic behavior. Recently we have demonstrated the possibility of implementing macroscopic engineering design approaches to construct DNA origami mechanisms (DOM) with programmable motion and tunable flexibility. Here, we implement the design of compliant DNA origami mechanisms to extend from prescribing motion to prescribing an energy landscape. Compliant mechanisms facilitate motion via deformation of components with tunable stiffness resulting in well-defined mechanical energy stored in the structure. We design, fabricate, and characterize a DNA origami nanostructure with an energy landscape defined by two stable states (local energy minima) separated by a designed energy barrier. This nanostructure is a four-bar bistable mechanism with two undeformed states. Traversing between those states requires deformation, and hence mechanical energy storage, in a compliant arm of the linkage. The energy barrier for switching between two states was obtained from the conformational distribution based on a Boltzmann probability function and closely follows a predictive mechanical model. Furthermore, we demonstrated the ability to actuate the mechanism into one stable state via additional DNA inputs and then release the actuation via DNA strand displacement. This controllable multistate system establishes a foundation for direct design of energy landscapes that regulate conformational dynamics similar to biomolecular complexes.

  10. Incorporating Renewable Energy Science in Regional Landscape Design: Results from a Competition in The Netherlands

    Directory of Open Access Journals (Sweden)

    Renée M. de Waal

    2015-04-01

    Full Text Available Energy transition is expected to make an important contribution to sustainable development. Although it is argued that landscape design could foster energy transition, there is scant empirical research on how practitioners approach this new challenge. The research question central to this study is: To what extent and how is renewable energy science incorporated in regional landscape design? To address this knowledge gap, a case study of a regional landscape design competition in the Netherlands, held from 2010–2012, is presented. Its focus was on integral, strategic landscape transformation with energy transition as a major theme. Content analysis of the 36 competition entries was supplemented and triangulated with a survey among the entrants, observation of the process and a study of the competition documents and website. Results indicated insufficient use of key-strategies elaborated by renewable energy science. If landscape design wants to adopt a supportive role towards energy transition, a well-informed and evidence-based approach is highly recommended. Nevertheless, promising strategies for addressing the complex process of ensuring sustainable energy transition also emerged. They include the careful cultivation of public support by developing inclusive and bottom-up processes, and balancing energy-conscious interventions with other land uses and interests.

  11. Connecting the kinetics and energy landscape of tRNA translocation on the ribosome.

    Directory of Open Access Journals (Sweden)

    Paul C Whitford

    Full Text Available Functional rearrangements in biomolecular assemblies result from diffusion across an underlying energy landscape. While bulk kinetic measurements rely on discrete state-like approximations to the energy landscape, single-molecule methods can project the free energy onto specific coordinates. With measures of the diffusion, one may establish a quantitative bridge between state-like kinetic measurements and the continuous energy landscape. We used an all-atom molecular dynamics simulation of the 70S ribosome (2.1 million atoms; 1.3 microseconds to provide this bridge for specific conformational events associated with the process of tRNA translocation. Starting from a pre-translocation configuration, we identified sets of residues that collectively undergo rotary rearrangements implicated in ribosome function. Estimates of the diffusion coefficients along these collective coordinates for translocation were then used to interconvert between experimental rates and measures of the energy landscape. This analysis, in conjunction with previously reported experimental rates of translocation, provides an upper-bound estimate of the free-energy barriers associated with translocation. While this analysis was performed for a particular kinetic scheme of translocation, the quantitative framework is general and may be applied to energetic and kinetic descriptions that include any number of intermediates and transition states.

  12. Energy landscapes for a machine learning application to series data

    Energy Technology Data Exchange (ETDEWEB)

    Ballard, Andrew J.; Stevenson, Jacob D.; Das, Ritankar; Wales, David J., E-mail: dw34@cam.ac.uk [University Chemical Laboratories, Lensfield Road, Cambridge CB2 1EW (United Kingdom)

    2016-03-28

    Methods developed to explore and characterise potential energy landscapes are applied to the corresponding landscapes obtained from optimisation of a cost function in machine learning. We consider neural network predictions for the outcome of local geometry optimisation in a triatomic cluster, where four distinct local minima exist. The accuracy of the predictions is compared for fits using data from single and multiple points in the series of atomic configurations resulting from local geometry optimisation and for alternative neural networks. The machine learning solution landscapes are visualised using disconnectivity graphs, and signatures in the effective heat capacity are analysed in terms of distributions of local minima and their properties.

  13. Energy landscapes for a machine learning application to series data

    International Nuclear Information System (INIS)

    Ballard, Andrew J.; Stevenson, Jacob D.; Das, Ritankar; Wales, David J.

    2016-01-01

    Methods developed to explore and characterise potential energy landscapes are applied to the corresponding landscapes obtained from optimisation of a cost function in machine learning. We consider neural network predictions for the outcome of local geometry optimisation in a triatomic cluster, where four distinct local minima exist. The accuracy of the predictions is compared for fits using data from single and multiple points in the series of atomic configurations resulting from local geometry optimisation and for alternative neural networks. The machine learning solution landscapes are visualised using disconnectivity graphs, and signatures in the effective heat capacity are analysed in terms of distributions of local minima and their properties.

  14. Structural and kinetic mapping of side-chain exposure onto the protein energy landscape.

    Science.gov (United States)

    Bernstein, Rachel; Schmidt, Kierstin L; Harbury, Pehr B; Marqusee, Susan

    2011-06-28

    Identification and characterization of structural fluctuations that occur under native conditions is crucial for understanding protein folding and function, but such fluctuations are often rare and transient, making them difficult to study. Native-state hydrogen exchange (NSHX) has been a powerful tool for identifying such rarely populated conformations, but it generally reveals no information about the placement of these species along the folding reaction coordinate or the barriers separating them from the folded state and provides little insight into side-chain packing. To complement such studies, we have performed native-state alkyl-proton exchange, a method analogous to NSHX that monitors cysteine modification rather than backbone amide exchange, to examine the folding landscape of Escherichia coli ribonuclease H, a protein well characterized by hydrogen exchange. We have chosen experimental conditions such that the rate-limiting barrier acts as a kinetic partition: residues that become exposed only upon crossing the unfolding barrier are modified in the EX1 regime (alkylation rates report on the rate of unfolding), while those exposed on the native side of the barrier are modified predominantly in the EX2 regime (alkylation rates report on equilibrium populations). This kinetic partitioning allows for identification and placement of partially unfolded forms along the reaction coordinate. Using this approach we detect previously unidentified, rarely populated conformations residing on the native side of the barrier and identify side chains that are modified only upon crossing the unfolding barrier. Thus, in a single experiment under native conditions, both sides of the rate-limiting barrier are investigated.

  15. An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.

    Science.gov (United States)

    Boldt, Karsten; van Reeuwijk, Jeroen; Lu, Qianhao; Koutroumpas, Konstantinos; Nguyen, Thanh-Minh T; Texier, Yves; van Beersum, Sylvia E C; Horn, Nicola; Willer, Jason R; Mans, Dorus A; Dougherty, Gerard; Lamers, Ideke J C; Coene, Karlien L M; Arts, Heleen H; Betts, Matthew J; Beyer, Tina; Bolat, Emine; Gloeckner, Christian Johannes; Haidari, Khatera; Hetterschijt, Lisette; Iaconis, Daniela; Jenkins, Dagan; Klose, Franziska; Knapp, Barbara; Latour, Brooke; Letteboer, Stef J F; Marcelis, Carlo L; Mitic, Dragana; Morleo, Manuela; Oud, Machteld M; Riemersma, Moniek; Rix, Susan; Terhal, Paulien A; Toedt, Grischa; van Dam, Teunis J P; de Vrieze, Erik; Wissinger, Yasmin; Wu, Ka Man; Apic, Gordana; Beales, Philip L; Blacque, Oliver E; Gibson, Toby J; Huynen, Martijn A; Katsanis, Nicholas; Kremer, Hannie; Omran, Heymut; van Wijk, Erwin; Wolfrum, Uwe; Kepes, François; Davis, Erica E; Franco, Brunella; Giles, Rachel H; Ueffing, Marius; Russell, Robert B; Roepman, Ronald

    2016-05-13

    Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine.

  16. Peptide Free Energy Landscapes Calibrated by Molecular Orbital Calculations

    OpenAIRE

    Ono, S.; Kuroda, M.; Higo, J.; Kamiya, N.; Nakajima, N.; Nakamura, H.

    2002-01-01

    Free energy landscapes of peptide conformations werecalibrated by ab initiomolecular orbital calculations, after enhancedconformational sampling using the multicanonical molecular dynamicssimulations. Three different potentials of mean force for an isolateddipeptide were individually obtained using the conventional force fields,AMBER parm94, AMBER parm96, and CHARMm22. Each potential ofmean force was calibrated based on the umbrella sampling algorithm fromthe adiabatic energy map that was cal...

  17. Free energy landscape and transition pathways from Watson–Crick to Hoogsteen base pairing in free duplex DNA

    Science.gov (United States)

    Yang, Changwon; Kim, Eunae; Pak, Youngshang

    2015-01-01

    Houghton (HG) base pairing plays a central role in the DNA binding of proteins and small ligands. Probing detailed transition mechanism from Watson–Crick (WC) to HG base pair (bp) formation in duplex DNAs is of fundamental importance in terms of revealing intrinsic functions of double helical DNAs beyond their sequence determined functions. We investigated a free energy landscape of a free B-DNA with an adenosine–thymine (A–T) rich sequence to probe its conformational transition pathways from WC to HG base pairing. The free energy landscape was computed with a state-of-art two-dimensional umbrella molecular dynamics simulation at the all-atom level. The present simulation showed that in an isolated duplex DNA, the spontaneous transition from WC to HG bp takes place via multiple pathways. Notably, base flipping into the major and minor grooves was found to play an important role in forming these multiple transition pathways. This finding suggests that naked B-DNA under normal conditions has an inherent ability to form HG bps via spontaneous base opening events. PMID:26250116

  18. Energy Landscape and Pathways for Transitions between Watson-Crick and Hoogsteen Base Pairing in DNA.

    Science.gov (United States)

    Chakraborty, Debayan; Wales, David J

    2018-01-04

    The recent discovery that Hoogsteen (HG) base pairs are widespread in DNA across diverse sequences and positional contexts could have important implications for understanding DNA replication and DNA-protein recognition. While evidence is emerging that the Hoogsteen conformation could be a thermodynamically accessible conformation of the DNA duplex and provide a means to expand its functionality, relatively little is known about the molecular mechanism underlying the Watson-Crick (WC) to HG transition. In this Perspective, we describe pathways and kinetics for this transition at an atomic level of detail, using the energy landscape perspective. We show that competition between the duplex conformations results in a double funnel landscape, which explains some recent experimental observations. The interconversion pathways feature a number of intermediates, with a variable number of WC and HG base pairs. The relatively slow kinetics, with possible deviations from two-state behavior, suggest that this conformational switch is likely to be a challenging target for both simulation and experiment.

  19. Energy landscape reveals that the budding yeast cell cycle is a robust and adaptive multi-stage process.

    Directory of Open Access Journals (Sweden)

    Cheng Lv

    2015-03-01

    Full Text Available Quantitatively understanding the robustness, adaptivity and efficiency of cell cycle dynamics under the influence of noise is a fundamental but difficult question to answer for most eukaryotic organisms. Using a simplified budding yeast cell cycle model perturbed by intrinsic noise, we systematically explore these issues from an energy landscape point of view by constructing an energy landscape for the considered system based on large deviation theory. Analysis shows that the cell cycle trajectory is sharply confined by the ambient energy barrier, and the landscape along this trajectory exhibits a generally flat shape. We explain the evolution of the system on this flat path by incorporating its non-gradient nature. Furthermore, we illustrate how this global landscape changes in response to external signals, observing a nice transformation of the landscapes as the excitable system approaches a limit cycle system when nutrients are sufficient, as well as the formation of additional energy wells when the DNA replication checkpoint is activated. By taking into account the finite volume effect, we find additional pits along the flat cycle path in the landscape associated with the checkpoint mechanism of the cell cycle. The difference between the landscapes induced by intrinsic and extrinsic noise is also discussed. In our opinion, this meticulous structure of the energy landscape for our simplified model is of general interest to other cell cycle dynamics, and the proposed methods can be applied to study similar biological systems.

  20. Renewable energy policy and landscape management in Andalusia, Spain: The facts

    International Nuclear Information System (INIS)

    Prados, Maria-Jose

    2010-01-01

    Renewable energy has developed spectacularly in Spain since the European Union started a process of energy policy reform. A review of Spanish State legislation on renewable energies confirms that the success in installing renewable energy is attributable to public aid. Andalusia is one of the autonomous communities, which has simultaneously developed the legal framework and very successfully implemented the introduction of renewable power. When implementing the central government's policy, the Andalusian regional government prioritised increases in both surface cover by wind and solar plants (thermal and photovoltaic energy) and in the number of companies involved. However, this development of renewable energies took place without any proper integration into regional spatial and landscape planning. This paper explores renewable power implementation in Andalusia through regulatory measures put in place over the last decade to develop renewable energy systems and the way they can be managed alongside planning issues. The location of large-scale renewable plants has had consequences for territory in the socio-political context of renewable energy promotion. The main findings focus on renewable energy plant sprawl throughout rural areas in Andalusia with no clear effect on landscape management and no firm backing from the local population.

  1. Protein Expression Landscape of Mouse Embryos during Pre-implantation Development

    Directory of Open Access Journals (Sweden)

    Yawei Gao

    2017-12-01

    Full Text Available Pre-implantation embryo development is an intricate and precisely regulated process orchestrated by maternally inherited proteins and newly synthesized proteins following zygotic genome activation. Although genomic and transcriptomic studies have enriched our understanding of the genetic programs underlying this process, the protein expression landscape remains unexplored. Using quantitative mass spectrometry, we identified nearly 5,000 proteins from 8,000 mouse embryos of each stage (zygote, 2-cell, 4-cell, 8-cell, morula, and blastocyst. We found that protein expression in zygotes, morulas, and blastocysts is distinct from 2- to 8-cell embryos. Analysis of protein phosphorylation identified critical kinases and signal transduction pathways. We highlight key factors and their important roles in embryo development. Combined analysis of transcriptomic and proteomic data reveals coordinated control of RNA degradation, transcription, and translation and identifies previously undefined exon-junction-derived peptides. Our study provides an invaluable resource for further mechanistic studies and suggests core factors regulating pre-implantation embryo development.

  2. Prion protein β2-α2 loop conformational landscape.

    Science.gov (United States)

    Caldarulo, Enrico; Barducci, Alessandro; Wüthrich, Kurt; Parrinello, Michele

    2017-09-05

    In transmissible spongiform encephalopathies (TSEs), which are lethal neurodegenerative diseases that affect humans and a wide range of other mammalian species, the normal "cellular" prion protein ([Formula: see text]) is transformed into amyloid aggregates representing the "scrapie form" of the protein ([Formula: see text]). Continued research on this system is of keen interest, since new information on the physiological function of [Formula: see text] in healthy organisms is emerging, as well as new data on the mechanism of the transformation of [Formula: see text] to [Formula: see text] In this paper we used two different approaches: a combination of the well-tempered ensemble (WTE) and parallel tempering (PT) schemes and metadynamics (MetaD) to characterize the conformational free-energy surface of [Formula: see text] The focus of the data analysis was on an 11-residue polypeptide segment in mouse [Formula: see text](121-231) that includes the [Formula: see text]2-[Formula: see text]2 loop of residues 167-170, for which a correlation between structure and susceptibility to prion disease has previously been described. This study includes wild-type mouse [Formula: see text] and a variant with the single-residue replacement Y169A. The resulting detailed conformational landscapes complement in an integrative manner the available experimental data on [Formula: see text], providing quantitative insights into the nature of the structural transition-related function of the [Formula: see text]2-[Formula: see text]2 loop.

  3. Free energy landscapes of electron transfer system in dipolar environment below and above the rotational freezing temperature

    International Nuclear Information System (INIS)

    Suzuki, Yohichi; Tanimura, Yoshitaka

    2007-01-01

    Electron transfer reaction in a polar solvent is modeled by a solute dipole surrounded by dipolar molecules with simple rotational dynamics posted on the three-dimensional distorted lattice sites. The interaction energy between the solute and solvent dipoles as a reaction coordinate is adopted and free energy landscapes are calculated by generating all possible states for a 26 dipolar system and by employing Wang-Landau sampling algorithm for a 92 dipolar system. For temperatures higher than the energy scale of dipole-dipole interactions, the free energy landscapes for the small reaction coordinate region have quadratic shape as predicted by Marcus [Rev. Mod. Phys. 65, 599 (1993)] whereas for the large reaction coordinate region, the landscapes exhibit a nonquadratic shape. When the temperature drops, small notched structures appear on the free energy profiles because of the frustrated interactions among dipoles. The formation of notched structure is analyzed with statistical approach and it is shown that the amplitude of notched structure depend upon the segment size of the reaction coordinate and is characterized by the interaction energy among the dipoles. Using simulated free energy landscapes, the authors calculate the reaction rates as a function of the energy gap for various temperatures. At high temperature, the reactions rates follow a bell shaped (inverted parabolic) energy gap law in the small energy gap regions, while it becomes steeper than the parabolic shape in a large energy gap regions due to the nonquadratic shape of the free energy landscape. The peak position of parabola also changes as the function of temperature. At low temperature, the profile of the reaction rates is no longer smooth because of the many local minima of the free energy landscape

  4. Prion protein β2–α2 loop conformational landscape

    Science.gov (United States)

    Caldarulo, Enrico; Wüthrich, Kurt; Parrinello, Michele

    2017-01-01

    In transmissible spongiform encephalopathies (TSEs), which are lethal neurodegenerative diseases that affect humans and a wide range of other mammalian species, the normal “cellular” prion protein (PrPC) is transformed into amyloid aggregates representing the “scrapie form” of the protein (PrPSc). Continued research on this system is of keen interest, since new information on the physiological function of PrPC in healthy organisms is emerging, as well as new data on the mechanism of the transformation of PrPC to PrPSc. In this paper we used two different approaches: a combination of the well-tempered ensemble (WTE) and parallel tempering (PT) schemes and metadynamics (MetaD) to characterize the conformational free-energy surface of PrPC. The focus of the data analysis was on an 11-residue polypeptide segment in mouse PrPC(121–231) that includes the β2–α2 loop of residues 167–170, for which a correlation between structure and susceptibility to prion disease has previously been described. This study includes wild-type mouse PrPC and a variant with the single-residue replacement Y169A. The resulting detailed conformational landscapes complement in an integrative manner the available experimental data on PrPC, providing quantitative insights into the nature of the structural transition-related function of the β2–α2 loop. PMID:28827331

  5. Control of the Effective Free-Energy Landscape in a Frustrated Magnet by a Field Pulse

    Science.gov (United States)

    Wan, Yuan; Moessner, Roderich

    2017-10-01

    Thermal fluctuations can lift the degeneracy of a ground state manifold, producing a free-energy landscape without accidentally degenerate minima. In a process known as order by disorder, a subset of states incorporating symmetry breaking may be selected. Here, we show that such a free-energy landscape can be controlled in a nonequilibrium setting as the slow motion within the ground state manifold is governed by the fast modes out of it. For the paradigmatic case of the classical pyrochlore X Y antiferromagnet, we show that a uniform magnetic field pulse can excite these fast modes to generate a tunable effective free-energy landscape with minima at thermodynamically unstable portions of the ground state manifold.

  6. Rural protein insufficiency in a wildlife-depleted West African farm-forest landscape.

    Directory of Open Access Journals (Sweden)

    Björn Schulte-Herbrüggen

    Full Text Available Wildlife is an important source of protein for many people in developing countries. Yet wildlife depletion due to overexploitation is common throughout the humid tropics and its effect on protein security, especially for vulnerable households, is poorly understood. This is problematic for both sustainable rural development and conservation management.This study investigates a key dimension of protein security in a cash-crop farming community living in a wildlife-depleted farm-forest landscape in SW Ghana, a region where protein-energy malnutrition persists. Specifically, we monitored protein sufficiency, defined as whether consumption met daily requirements, as benchmarked by recommended daily allowance (RDA. We focus on whether more vulnerable households were less likely to be able to meet their protein needs, where vulnerability was defined by wealth, agricultural season and gender of the household head. Our central hypothesis was: (a vulnerable households are less likely to consume sufficient protein. In the context that most plant proteins were home-produced, so likely relatively accessible to all households, while most animal proteins were purchased, so likely less accessible to vulnerable households, we tested two further hypotheses: (b vulnerable households depend more on plant protein to cover their protein needs; and (c vulnerable households are less likely to earn sufficient cash income to meet their protein needs through purchased animal sources.Between 14% and 60% of households (depending on plant protein content assumptions consumed less than the RDA for protein, but neither protein consumption nor protein sufficiency co-varied with household vulnerability. Fish, livestock and food crops comprised 85% of total protein intake and strongly affected protein sufficiency. However, bushmeat remained an important protein source (15% of total consumption, especially during the post-harvest season when it averaged 26% of total protein

  7. New Energy Landscapes of Pennsylvania: Forests to Farms to Fracking

    Science.gov (United States)

    Johnson, Deborah A.

    This dissertation adds to the literature on energy needed by industry, government, and citizens for decision-making. The pursuit to access or create new energy resources spawns new landscapes of energy in the early 21st century. The combination of hydraulic fracturing and horizontal drilling technologies---popularly called "fracking"---enables entry into previously inaccessible natural gas reserves such as the Marcellus shale much of which lies beneath Pennsylvania. Although this unconventional method offers a promising source of domestic energy and job growth, the potential for negative impacts raises concerns and questions. The questions include: What is the controversy about fracking in Pennsylvania? What are the impacts of fracking? What costs is Pennsylvania paying as it shifts to shale gas extraction? Are there activities taking place or material signs that point to the emerging new landscapes? Are the individuals and organizations that resist shale gas extraction---the so-called "Green Forces"---and others who live within the region of development more or less attuned to these costs? A mixed methods approach consists of landscape and stakeholder analyses including visual examination of GIS-generated maps, satellite images, and photos taken in the field specifically from four counties: Washington, Warren, McKean, and Bradford. Research captures stakeholders' voices across the public, government, and private sectors at different scales. A stakeholder matrix facilitates data organization and analysis. Data include 114 individual statements from an EPA Public Meeting, texts from 40 online-newspaper articles or blogs, and face-to-face interviews or focus group participation of 36 individuals. Further data come from a public health conference, industry convention, and public protest. The new energy landscape covers spaces in Pennsylvania where oil and gas development previously had not been present. It obscures as well as exposes the legacy of past energy

  8. The free energy landscape of small molecule unbinding.

    Directory of Open Access Journals (Sweden)

    Danzhi Huang

    2011-02-01

    Full Text Available The spontaneous dissociation of six small ligands from the active site of FKBP (the FK506 binding protein is investigated by explicit water molecular dynamics simulations and network analysis. The ligands have between four (dimethylsulphoxide and eleven (5-diethylamino-2-pentanone non-hydrogen atoms, and an affinity for FKBP ranging from 20 to 0.2 mM. The conformations of the FKBP/ligand complex saved along multiple trajectories (50 runs at 310 K for each ligand are grouped according to a set of intermolecular distances into nodes of a network, and the direct transitions between them are the links. The network analysis reveals that the bound state consists of several subbasins, i.e., binding modes characterized by distinct intermolecular hydrogen bonds and hydrophobic contacts. The dissociation kinetics show a simple (i.e., single-exponential time dependence because the unbinding barrier is much higher than the barriers between subbasins in the bound state. The unbinding transition state is made up of heterogeneous positions and orientations of the ligand in the FKBP active site, which correspond to multiple pathways of dissociation. For the six small ligands of FKBP, the weaker the binding affinity the closer to the bound state (along the intermolecular distance are the transition state structures, which is a new manifestation of Hammond behavior. Experimental approaches to the study of fragment binding to proteins have limitations in temporal and spatial resolution. Our network analysis of the unbinding simulations of small inhibitors from an enzyme paints a clear picture of the free energy landscape (both thermodynamics and kinetics of ligand unbinding.

  9. Free energy landscape and transition pathways from Watson-Crick to Hoogsteen base pairing in free duplex DNA.

    Science.gov (United States)

    Yang, Changwon; Kim, Eunae; Pak, Youngshang

    2015-09-18

    Houghton (HG) base pairing plays a central role in the DNA binding of proteins and small ligands. Probing detailed transition mechanism from Watson-Crick (WC) to HG base pair (bp) formation in duplex DNAs is of fundamental importance in terms of revealing intrinsic functions of double helical DNAs beyond their sequence determined functions. We investigated a free energy landscape of a free B-DNA with an adenosine-thymine (A-T) rich sequence to probe its conformational transition pathways from WC to HG base pairing. The free energy landscape was computed with a state-of-art two-dimensional umbrella molecular dynamics simulation at the all-atom level. The present simulation showed that in an isolated duplex DNA, the spontaneous transition from WC to HG bp takes place via multiple pathways. Notably, base flipping into the major and minor grooves was found to play an important role in forming these multiple transition pathways. This finding suggests that naked B-DNA under normal conditions has an inherent ability to form HG bps via spontaneous base opening events. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Inflation, Dark Matter, and Dark Energy in the String Landscape

    OpenAIRE

    Liddle, Andrew R; Ureña-López, L Arturo

    2006-01-01

    We consider the conditions needed to unify the description of dark matter, dark energy and inflation in the context of the string landscape. We find that incomplete decay of the inflaton field gives the possibility that a single field is responsible for all three phenomena. By contrast, unifying dark matter and dark energy into a single field, separate from the inflaton, appears rather difficult.

  11. Relationship between energy landscape and low-temperature dynamics of ±J spin glasses

    International Nuclear Information System (INIS)

    Kobe, S.; Krawczyk, J.

    2004-01-01

    Clusters and valleys in the exact low-energy landscape of finite Edwards-Anderson ±J spin glasses are related to the distribution of spin domains and free spins in the ground states. The time evolution of the spin correlation function reflects a walk through the landscape at a given temperature and shows typical glassy behaviour

  12. Accelerated weight histogram method for exploring free energy landscapes

    Energy Technology Data Exchange (ETDEWEB)

    Lindahl, V.; Lidmar, J.; Hess, B. [Department of Theoretical Physics and Swedish e-Science Research Center, KTH Royal Institute of Technology, 10691 Stockholm (Sweden)

    2014-07-28

    Calculating free energies is an important and notoriously difficult task for molecular simulations. The rapid increase in computational power has made it possible to probe increasingly complex systems, yet extracting accurate free energies from these simulations remains a major challenge. Fully exploring the free energy landscape of, say, a biological macromolecule typically requires sampling large conformational changes and slow transitions. Often, the only feasible way to study such a system is to simulate it using an enhanced sampling method. The accelerated weight histogram (AWH) method is a new, efficient extended ensemble sampling technique which adaptively biases the simulation to promote exploration of the free energy landscape. The AWH method uses a probability weight histogram which allows for efficient free energy updates and results in an easy discretization procedure. A major advantage of the method is its general formulation, making it a powerful platform for developing further extensions and analyzing its relation to already existing methods. Here, we demonstrate its efficiency and general applicability by calculating the potential of mean force along a reaction coordinate for both a single dimension and multiple dimensions. We make use of a non-uniform, free energy dependent target distribution in reaction coordinate space so that computational efforts are not wasted on physically irrelevant regions. We present numerical results for molecular dynamics simulations of lithium acetate in solution and chignolin, a 10-residue long peptide that folds into a β-hairpin. We further present practical guidelines for setting up and running an AWH simulation.

  13. Fitness landscape of the human immunodeficiency virus envelope protein that is targeted by antibodies

    Science.gov (United States)

    Louie, Raymond H. Y.; Kaczorowski, Kevin J.; Chakraborty, Arup K.; McKay, Matthew R.

    2018-01-01

    HIV is a highly mutable virus, and over 30 years after its discovery, a vaccine or cure is still not available. The isolation of broadly neutralizing antibodies (bnAbs) from HIV-infected patients has led to renewed hope for a prophylactic vaccine capable of combating the scourge of HIV. A major challenge is the design of immunogens and vaccination protocols that can elicit bnAbs that target regions of the virus’s spike proteins where the likelihood of mutational escape is low due to the high fitness cost of mutations. Related challenges include the choice of combinations of bnAbs for therapy. An accurate representation of viral fitness as a function of its protein sequences (a fitness landscape), with explicit accounting of the effects of coupling between mutations, could help address these challenges. We describe a computational approach that has allowed us to infer a fitness landscape for gp160, the HIV polyprotein that comprises the viral spike that is targeted by antibodies. We validate the inferred landscape through comparisons with experimental fitness measurements, and various other metrics. We show that an effective antibody that prevents immune escape must selectively bind to high escape cost residues that are surrounded by those where mutations incur a low fitness cost, motivating future applications of our landscape for immunogen design. PMID:29311326

  14. A deterministic method for estimating free energy genetic network landscapes with applications to cell commitment and reprogramming paths.

    Science.gov (United States)

    Olariu, Victor; Manesso, Erica; Peterson, Carsten

    2017-06-01

    Depicting developmental processes as movements in free energy genetic landscapes is an illustrative tool. However, exploring such landscapes to obtain quantitative or even qualitative predictions is hampered by the lack of free energy functions corresponding to the biochemical Michaelis-Menten or Hill rate equations for the dynamics. Being armed with energy landscapes defined by a network and its interactions would open up the possibility of swiftly identifying cell states and computing optimal paths, including those of cell reprogramming, thereby avoiding exhaustive trial-and-error simulations with rate equations for different parameter sets. It turns out that sigmoidal rate equations do have approximate free energy associations. With this replacement of rate equations, we develop a deterministic method for estimating the free energy surfaces of systems of interacting genes at different noise levels or temperatures. Once such free energy landscape estimates have been established, we adapt a shortest path algorithm to determine optimal routes in the landscapes. We explore the method on three circuits for haematopoiesis and embryonic stem cell development for commitment and reprogramming scenarios and illustrate how the method can be used to determine sequential steps for onsets of external factors, essential for efficient reprogramming.

  15. Detecting Repetitions and Periodicities in Proteins by Tiling the Structural Space

    OpenAIRE

    Parra, R. Gonzalo; Espada, Rocío; Sánchez, Ignacio E.; Sippl, Manfred J.; Ferreiro, Diego U.

    2013-01-01

    The notion of energy landscapes provides conceptual tools for understanding the complexities of protein folding and function. Energy landscape theory indicates that it is much easier to find sequences that satisfy the “Principle of Minimal Frustration” when the folded structure is symmetric (Wolynes, P. G. Symmetry and the Energy Landscapes of Biomolecules. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 14249–14255). Similarly, repeats and structural mosaics may be fundamentally related to landscape...

  16. Impacts of renewable energy on landscape. Alternative of offshore wind in marine areas

    Directory of Open Access Journals (Sweden)

    Francesca Moraci

    2014-01-01

    Full Text Available The effects determined in the landscape by plants powered by renewable sources represent some unresolved issues in terms of visual and landscape impact mitigation in general. These aspects relate to the landscape are recognized in all types of impact with due attention to the various components and dynamics involved identifiable in the landscape of reference.The wind power plants, in particular, while making unquestionable environmental benefits thanks to the production of energy from renewable sources, but imposes a significant cost to the landscape with the installation of wind turbines in contexts necessarily favorable to impact,  interrupting the skyline, creating territorial discontinuities, "subtracting" and altering the landscape in the absence of effective mitigation works.The environmental compatibility of the proposed solutions depends primarily on the location of wind farms.Is necessary indicate  an overall strategy, a shared model of planning and land management, as in other European countries such as Denmark, Germany, France and the United Kingdom where the choice of locating wind farms has resulted in a new draft territory, construction and redesign of the landscape.

  17. Free Energy Landscapes of Alanine Oligopeptides in Rigid-Body and Hybrid Water Models.

    Science.gov (United States)

    Nayar, Divya; Chakravarty, Charusita

    2015-08-27

    Replica exchange molecular dynamics is used to study the effect of different rigid-body (mTIP3P, TIP4P, SPC/E) and hybrid (H1.56, H3.00) water models on the conformational free energy landscape of the alanine oligopeptides (acAnme and acA5nme), in conjunction with the CHARMM22 force field. The free energy landscape is mapped out as a function of the Ramachandran angles. In addition, various secondary structure metrics, solvation shell properties, and the number of peptide-solvent hydrogen bonds are monitored. Alanine dipeptide is found to have similar free energy landscapes in different solvent models, an insensitivity which may be due to the absence of possibilities for forming i-(i + 4) or i-(i + 3) intrapeptide hydrogen bonds. The pentapeptide, acA5nme, where there are three intrapeptide backbone hydrogen bonds, shows a conformational free energy landscape with a much greater degree of sensitivity to the choice of solvent model, though the three rigid-body water models differ only quantitatively. The pentapeptide prefers nonhelical, non-native PPII and β-sheet populations as the solvent is changed from SPC/E to the less tetrahedral liquid (H1.56) to an LJ-like liquid (H3.00). The pentapeptide conformational order metrics indicate a preference for open, solvent-exposed, non-native structures in hybrid solvent models at all temperatures of study. The possible correlations between the properties of solvent models and secondary structure preferences of alanine oligopeptides are discussed, and the competition between intrapeptide, peptide-solvent, and solvent-solvent hydrogen bonding is shown to be crucial in the relative free energies of different conformers.

  18. Energy landscape for martensitic phase transformation in shape memory NiTi

    International Nuclear Information System (INIS)

    Kibey, S.; Sehitoglu, H.; Johnson, D.D.

    2009-01-01

    First-principles calculations are presented for parent B2 phase and martensitic B19 and B19' phases in NiTi. The results indicate that both B19 and B19' are energetically more stable than the parent B2 phase. By means of ab initio density functional theory, the complete distortion-shuffle energy landscape associated with B2 → B19 transformation in NiTi is then determined. In addition to accounting for the Bain-type deformation through the Cauchy-Born rule, the study explicitly accounts for the shuffle displacements experienced by the internal ions in NiTi. The energy landscape allows the energy barrier associated with the B2 → B19 transformation pathway to be identified. The results indicate that a barrier of 0.48 mRyd atom -1 (relative to the B2 phase) must be overcome to transform the parent B2 NiTi to orthorhombic B19 martensite

  19. Deorphanizing the human transmembrane genome: A landscape of uncharacterized membrane proteins.

    Science.gov (United States)

    Babcock, Joseph J; Li, Min

    2014-01-01

    The sequencing of the human genome has fueled the last decade of work to functionally characterize genome content. An important subset of genes encodes membrane proteins, which are the targets of many drugs. They reside in lipid bilayers, restricting their endogenous activity to a relatively specialized biochemical environment. Without a reference phenotype, the application of systematic screens to profile candidate membrane proteins is not immediately possible. Bioinformatics has begun to show its effectiveness in focusing the functional characterization of orphan proteins of a particular functional class, such as channels or receptors. Here we discuss integration of experimental and bioinformatics approaches for characterizing the orphan membrane proteome. By analyzing the human genome, a landscape reference for the human transmembrane genome is provided.

  20. Comparison of Recent Oil and Gas, Wind Energy, and Other Anthropogenic Landscape Alteration Factors in Texas Through 2014.

    Science.gov (United States)

    Pierre, Jon Paul; Wolaver, Brad D; Labay, Benjamin J; LaDuc, Travis J; Duran, Charles M; Ryberg, Wade A; Hibbitts, Toby J; Andrews, John R

    2018-05-01

    Recent research assessed how hydrocarbon and wind energy expansion has altered the North American landscape. Less understood, however, is how this energy development compares to other anthropogenic land use changes. Texas leads U.S. hydrocarbon production and wind power generation and has a rapidly expanding population. Thus, for ~47% of Texas (~324,000 km 2 ), we mapped the 2014 footprint of energy activities (~665,000 oil and gas wells, ~5700 wind turbines, ~237,000 km oil and gas pipelines, and ~2000 km electrical transmission lines). We compared the footprint of energy development to non-energy-related activities (agriculture, roads, urbanization) and found direct landscape alteration from all factors affects ~23% of the study area (~76,000 km 2 ), led by agriculture (~16%; ~52,882 km 2 ). Oil and gas activities altered turbine pads and ~10 km 2 from power transmission lines. We found that edge effects of widely-distributed energy infrastructure caused more indirect landscape alteration than larger, more concentrated urbanization and agriculture. This study presents a novel technique to quantify and compare anthropogenic activities causing both direct and indirect landscape alteration. We illustrate this landscape-mapping framework in Texas for the Spot-tailed Earless Lizard (Holbrookia lacerata); however, the approach can be applied to a range of species in developing regions globally.

  1. Energy landscape scheme for an intuitive understanding of complex domain dynamics in ferroelectric thin films

    Science.gov (United States)

    Heon Kim, Tae; Yoon, Jong-Gul; Hyub Baek, Seung; Park, Woong-Kyu; Mo Yang, Sang; Yup Jang, Seung; Min, Taeyuun; Chung, Jin-Seok; Eom, Chang-Beom; Won Noh, Tae

    2015-07-01

    Fundamental understanding of domain dynamics in ferroic materials has been a longstanding issue because of its relevance to many systems and to the design of nanoscale domain-wall devices. Despite many theoretical and experimental studies, a full understanding of domain dynamics still remains incomplete, partly due to complex interactions between domain-walls and disorder. We report domain-shape-preserving deterministic domain-wall motion, which directly confirms microscopic return point memory, by observing domain-wall breathing motion in ferroelectric BiFeO3 thin film using stroboscopic piezoresponse force microscopy. Spatial energy landscape that provides new insights into domain dynamics is also mapped based on the breathing motion of domain walls. The evolution of complex domain structure can be understood by the process of occupying the lowest available energy states of polarization in the energy landscape which is determined by defect-induced internal fields. Our result highlights a pathway for the novel design of ferroelectric domain-wall devices through the engineering of energy landscape using defect-induced internal fields such as flexoelectric fields.

  2. Energy landscape scheme for an intuitive understanding of complex domain dynamics in ferroelectric thin films.

    Science.gov (United States)

    Kim, Tae Heon; Yoon, Jong-Gul; Baek, Seung Hyub; Park, Woong-kyu; Yang, Sang Mo; Yup Jang, Seung; Min, Taeyuun; Chung, Jin-Seok; Eom, Chang-Beom; Noh, Tae Won

    2015-07-01

    Fundamental understanding of domain dynamics in ferroic materials has been a longstanding issue because of its relevance to many systems and to the design of nanoscale domain-wall devices. Despite many theoretical and experimental studies, a full understanding of domain dynamics still remains incomplete, partly due to complex interactions between domain-walls and disorder. We report domain-shape-preserving deterministic domain-wall motion, which directly confirms microscopic return point memory, by observing domain-wall breathing motion in ferroelectric BiFeO3 thin film using stroboscopic piezoresponse force microscopy. Spatial energy landscape that provides new insights into domain dynamics is also mapped based on the breathing motion of domain walls. The evolution of complex domain structure can be understood by the process of occupying the lowest available energy states of polarization in the energy landscape which is determined by defect-induced internal fields. Our result highlights a pathway for the novel design of ferroelectric domain-wall devices through the engineering of energy landscape using defect-induced internal fields such as flexoelectric fields.

  3. Quantitative analysis of the publishing landscape in high-energy physics

    International Nuclear Information System (INIS)

    Mele, Salvatore; Dallman, David; Vigen, Jens; Yeomans, Joanne

    2006-01-01

    World-wide collaboration in high-energy physics (HEP) is a tradition which dates back several decades, with scientific publications mostly coauthored by scientists from different countries. This coauthorship phenomenon makes it difficult to identify precisely the 'share' of each country in HEP scientific production. One year's worth of HEP scientific articles published in peer-reviewed journals is analysed and their authors are uniquely assigned to countries. This method allows the first correct estimation on a pro rata basis of the share of HEP scientific publishing among several countries and institutions. The results provide an interesting insight into the geographical collaborative patterns of the HEP community. The HEP publishing landscape is further analysed to provide information on the journals favoured by the HEP community and on the geographical variation of their author bases. These results provide quantitative input to the ongoing debate on the possible transition of HEP publishing to an Open Access model. Foreword. This paper reports the results of a recent detailed study of the publishing landscape in high energy physics. We thought that because of its direct relevance to the high energy physics community, this important quantitative input to the debate on the transition to Open Access naturally finds its place in our journal. Marc Henneaux, JHEP Scientific Director

  4. Calculation of the Local Free Energy Landscape in the Restricted Region by the Modified Tomographic Method.

    Science.gov (United States)

    Chen, Changjun

    2016-03-31

    The free energy landscape is the most important information in the study of the reaction mechanisms of the molecules. However, it is difficult to calculate. In a large collective variable space, a molecule must take a long time to obtain the sufficient sampling during the simulation. To save the calculation quantity, decreasing the sampling region and constructing the local free energy landscape is required in practice. However, the restricted region in the collective variable space may have an irregular shape. Simply restricting one or more collective variables of the molecule cannot satisfy the requirement. In this paper, we propose a modified tomographic method to perform the simulation. First, it divides the restricted region by some hyperplanes and connects the centers of hyperplanes together by a curve. Second, it forces the molecule to sample on the curve and the hyperplanes in the simulation and calculates the free energy data on them. Finally, all the free energy data are combined together to form the local free energy landscape. Without consideration of the area outside the restricted region, this free energy calculation can be more efficient. By this method, one can further optimize the path quickly in the collective variable space.

  5. Trp-cage: Folding free energy landscape in explicit water

    Science.gov (United States)

    Zhou, Ruhong

    2003-11-01

    Trp-cage is a 20-residue miniprotein, which is believed to be the fastest folder known so far. In this study, the folding free energy landscape of Trp-cage has been explored in explicit solvent by using an OPLSAA force field with periodic boundary condition. A highly parallel replica exchange molecular dynamics method is used for the conformation space sampling, with the help of a recently developed efficient molecular dynamics algorithm P3ME/RESPA (particle-particle particle-mesh Ewald/reference system propagator algorithm). A two-step folding mechanism is proposed that involves an intermediate state where two correctly formed partial hydrophobic cores are separated by an essential salt-bridge between residues Asp-9 and Arg-16 near the center of the peptide. This metastable intermediate state provides an explanation for the superfast folding process. The free energy landscape is found to be rugged at low temperatures, and then becomes smooth and funnel-like above 340 K. The lowest free energy structure at 300 K is only 1.50 Å C-RMSD (C-rms deviation) from the NMR structures. The simulated nuclear Overhauser effect pair distances are in excellent agreement with the raw NMR data. The temperature dependence of the Trp-cage population, however, is found to be significantly different from experiment, with a much higher melting transition temperature above 400 K (experimental 315 K), indicating that the current force fields, parameterized at room temperature, need to be improved to correctly predict the temperature dependence.

  6. A new approach to quantify semiochemical effects on insects based on energy landscapes.

    Directory of Open Access Journals (Sweden)

    Rory P Wilson

    Full Text Available Our ability to document insect preference for semiochemicals is pivotal in pest control as these agents can improve monitoring and be deployed within integrated pest management programmes for more efficacious control of pest species. However, methods used to date have drawbacks that limit their utility. We present and test a new concept for determining insect motivation to move towards, or away from, semiochemicals by noting direction and speed of movement as animals work against a defined energy landscape (environmentally dependent variation in the cost of transport requiring different powers to negotiate. We conducted trials with the pine weevils Hylobius abietis and peach-potato aphids Myzus persicae exposed to various attractants and repellents and placed so that they either moved up defined slopes against gravity or had to travel over variously rough surfaces.Linear Mixed Models demonstrated clear reductions in travel speed by insects moving along increasingly energetically taxing energy landscapes but also that responses varied according to different semiochemicals, thus highlighting the value of energy landscapes as a new concept to help measure insect motivation to access or avoid different attractants or repellents across individuals.New sensitive, detailed indicators of insect motivation derived from this approach should prove important in pest control across the world.

  7. Landscape management for sustainable supplies of bio energy feedstock and enhanced soil quality

    International Nuclear Information System (INIS)

    Douglas, K.; Muth, D.

    2013-01-01

    Agriculture can simultaneously address global food, feed, fiber, and energy challenges provided our soil, water, and air resources are not compromised in doing so. Our objective is to present a landscape management concept as an approach for integrating multiple bio energy feedstock sources into current crop production systems. This is done to show how multiple, increasing global challenges can be met in a sustainable manner. We discuss how collaborative research among Usda-Agricultural Research Service (ARS), US Department of Energy (DOE) Idaho National Laboratory (INL), several university extension and research partners, and industry representatives [known as the Renewable Energy Assessment Project (Reap) team] has led to the development of computer-based decision aids for guiding sustainable bio energy feedstock production. The decision aids, known initially as the Corn Stover Tool and more recently as the Landscape Environmental Assessment Framework (Leaf) are tools designed to recognize the importance of nature s diversity and can therefore be used to guide sustainable feedstock production without having negative impacts on critical ecosystem services. Using a 57 ha farm site in central Iowa, USA, we show how producer decisions regarding corn (Zea mays L.) stover harvest within the US Corn Belt can be made in a more sustainable manner. This example also supports Reap team conclusions that stover should not be harvested if average grain yields are less than 11 Mg ha-1 unless more balanced landscape management practices are implemented. The tools also illustrate the importance of sub-field management and site-specific stover harvest strategies

  8. Relaxation height in energy landscapes : an application to multiple metastable states

    NARCIS (Netherlands)

    Cirillo, E.N.M.; Nardi, F.R.

    2012-01-01

    The study of systems with multiple (not necessarily degenerate) metastable states presents subtle difficulties from the mathematical point of view related to the variational problem that has to be solved in these cases. We introduce the notion of relaxation height in a general energy landscape and

  9. Dairy Proteins and Energy Balance

    DEFF Research Database (Denmark)

    Bendtsen, Line Quist

    High protein diets affect energy balance beneficially through decreased hunger, enhanced satiety and increased energy expenditure. Dairy products are a major source of protein. Dairy proteins are comprised of two classes, casein (80%) and whey proteins (20%), which are both of high quality......, but casein is absorbed slowly and whey is absorbed rapidly. The present PhD study investigated the effects of total dairy proteins, whey, and casein, on energy balance and the mechanisms behind any differences in the effects of the specific proteins. The results do not support the hypothesis that dairy...... proteins, whey or casein are more beneficial than other protein sources in the regulation of energy balance, and suggest that dairy proteins, whey or casein seem to play only a minor role, if any, in the prevention and treatment of obesity....

  10. Probing Free-Energy Surfaces with Differential Scanning Calorimetry

    Science.gov (United States)

    Sanchez-Ruiz, Jose M.

    2011-05-01

    Many aspects of protein folding can be understood in terms of projections of the highly dimensional energy landscape onto a few (or even only one) particularly relevant coordinates. These free-energy surfaces can be probed conveniently from experimental differential scanning calorimetry (DSC) thermograms, as DSC provides a direct relation with the protein partition function. Free-energy surfaces thus obtained are consistent with two fundamental scenarios predicted by the energy-landscape perspective: (a) well-defined macrostates separated by significant free-energy barriers, in some cases, and, in many other cases, (b) marginal or even vanishingly small barriers, which furthermore show a good correlation with kinetics for fast- and ultrafast-folding proteins. Overall, the potential of DSC to assess free-energy surfaces for a wide variety of proteins makes it possible to address fundamental issues, such as the molecular basis of the barrier modulations produced by natural selection in response to functional requirements or to ensure kinetic stability.

  11. Constructing a folding model for protein S6 guided by native fluctuations deduced from NMR structures

    International Nuclear Information System (INIS)

    Lammert, Heiko; Noel, Jeffrey K.; Haglund, Ellinor; Onuchic, José N.; Schug, Alexander

    2015-01-01

    The diversity in a set of protein nuclear magnetic resonance (NMR) structures provides an estimate of native state fluctuations that can be used to refine and enrich structure-based protein models (SBMs). Dynamics are an essential part of a protein’s functional native state. The dynamics in the native state are controlled by the same funneled energy landscape that guides the entire folding process. SBMs apply the principle of minimal frustration, drawn from energy landscape theory, to construct a funneled folding landscape for a given protein using only information from the native structure. On an energy landscape smoothed by evolution towards minimal frustration, geometrical constraints, imposed by the native structure, control the folding mechanism and shape the native dynamics revealed by the model. Native-state fluctuations can alternatively be estimated directly from the diversity in the set of NMR structures for a protein. Based on this information, we identify a highly flexible loop in the ribosomal protein S6 and modify the contact map in a SBM to accommodate the inferred dynamics. By taking into account the probable native state dynamics, the experimental transition state is recovered in the model, and the correct order of folding events is restored. Our study highlights how the shared energy landscape connects folding and function by showing that a better description of the native basin improves the prediction of the folding mechanism

  12. Relationship between energy systems and landscapes. Guidelines and tools for design and management

    Directory of Open Access Journals (Sweden)

    Elisabetta Ginelli

    2014-10-01

    Full Text Available Landscapes undergoing conservation, valorisation, management and reconstruction policies, become a fundamental factor for the local/global development of natural, cultural, human and social potentials of territories. With the contribution of technological design culture, the research, having a strong multidisciplinary character, focuses on managing the relationship between energy systems and landscapes with the general aim of subverting and transforming apparent conflicts in synergies, in order to overcome a sectorial and segmented approach barely based on energy performances. Through the introduction of a complex multidimensional methodology of analysis and evaluation the goal of this work, is to develop standards of acceptability, meta-design criteria and guidelines for design, intro- ducing a methodology for multidimen- sional complex analysis and evaluation, to support Public Authorities.

  13. Monitoring Forest Change in Landscapes Under-Going Rapid Energy Development: Challenges and New Perspectives

    Directory of Open Access Journals (Sweden)

    Paul D. Pickell

    2014-07-01

    Full Text Available The accelerated development of energy resources around the world has substantially increased forest change related to oil and gas activities. In some cases, oil and gas activities are the primary catalyst of land-use change in forested landscapes. We discuss the challenges associated with characterizing ecological change related to energy resource development using North America as an exemplar. We synthesize the major impacts of energy development to forested ecosystems and offer new perspectives on how to detect and monitor anthropogenic disturbance during the Anthropocene. The disturbance of North American forests for energy development has resulted in persistent linear corridors, suppression of historical disturbance regimes, novel ecosystems, and the eradication of ecological memory. Characterizing anthropogenic disturbances using conventional patch-based disturbance measures will tend to underestimate the ecological impacts of energy development. Suitable indicators of anthropogenic impacts in forests should be derived from the integration of multi-scalar Earth observations. Relating these indicators to ecosystem condition will be a capstone in the progress toward monitoring forest change in landscapes undergoing rapid energy development.

  14. Counteracting chemical chaperone effects on the single-molecule α-synuclein structural landscape

    OpenAIRE

    Ferreon, Allan Chris M.; Moosa, Mahdi Muhammad; Gambin, Yann; Deniz, Ashok A.

    2012-01-01

    Protein structure and function depend on a close interplay between intrinsic folding energy landscapes and the chemistry of the protein environment. Osmolytes are small-molecule compounds that can act as chemical chaperones by altering the environment in a cellular context. Despite their importance, detailed studies on the role of these chemical chaperones in modulating structure and dimensions of intrinsically disordered proteins have been limited. Here, we used single-molecule Förster reson...

  15. Statistical topography of fitness landscapes

    OpenAIRE

    Franke, Jasper

    2011-01-01

    Fitness landscapes are generalized energy landscapes that play an important conceptual role in evolutionary biology. These landscapes provide a relation between the genetic configuration of an organism and that organism’s adaptive properties. In this work, global topographical features of these fitness landscapes are investigated using theoretical models. The resulting predictions are compared to empirical landscapes. It is shown that these landscapes allow, at least with respe...

  16. Navigating the conformational landscape of G protein-coupled receptor kinases during allosteric activation.

    Science.gov (United States)

    Yao, Xin-Qiu; Cato, M Claire; Labudde, Emily; Beyett, Tyler S; Tesmer, John J G; Grant, Barry J

    2017-09-29

    G protein-coupled receptors (GPCRs) are essential for transferring extracellular signals into carefully choreographed intracellular responses controlling diverse aspects of cell physiology. The duration of GPCR-mediated signaling is primarily regulated via GPCR kinase (GRK)-mediated phosphorylation of activated receptors. Although many GRK structures have been reported, the mechanisms underlying GRK activation are not well-understood, in part because it is unknown how these structures map to the conformational landscape available to this enzyme family. Unlike most other AGC kinases, GRKs rely on their interaction with GPCRs for activation and not phosphorylation. Here, we used principal component analysis of available GRK and protein kinase A crystal structures to identify their dominant domain motions and to provide a framework that helps evaluate how close each GRK structure is to being a catalytically competent state. Our results indicated that disruption of an interface formed between the large lobe of the kinase domain and the regulator of G protein signaling homology domain (RHD) is highly correlated with establishment of the active conformation. By introducing point mutations in the GRK5 RHD-kinase domain interface, we show with both in silico and in vitro experiments that perturbation of this interface leads to higher phosphorylation activity. Navigation of the conformational landscape defined by this bioinformatics-based study is likely common to all GPCR-activated GRKs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Bayesian energy landscape tilting: towards concordant models of molecular ensembles.

    Science.gov (United States)

    Beauchamp, Kyle A; Pande, Vijay S; Das, Rhiju

    2014-03-18

    Predicting biological structure has remained challenging for systems such as disordered proteins that take on myriad conformations. Hybrid simulation/experiment strategies have been undermined by difficulties in evaluating errors from computational model inaccuracies and data uncertainties. Building on recent proposals from maximum entropy theory and nonequilibrium thermodynamics, we address these issues through a Bayesian energy landscape tilting (BELT) scheme for computing Bayesian hyperensembles over conformational ensembles. BELT uses Markov chain Monte Carlo to directly sample maximum-entropy conformational ensembles consistent with a set of input experimental observables. To test this framework, we apply BELT to model trialanine, starting from disagreeing simulations with the force fields ff96, ff99, ff99sbnmr-ildn, CHARMM27, and OPLS-AA. BELT incorporation of limited chemical shift and (3)J measurements gives convergent values of the peptide's α, β, and PPII conformational populations in all cases. As a test of predictive power, all five BELT hyperensembles recover set-aside measurements not used in the fitting and report accurate errors, even when starting from highly inaccurate simulations. BELT's principled framework thus enables practical predictions for complex biomolecular systems from discordant simulations and sparse data. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  18. An energy landscape based approach for studying supercooled liquid and glassy thin films

    Science.gov (United States)

    Shah, Pooja; Mittal, Jeetain; Truskett, Thomas M.

    2004-03-01

    Materials in confined spaces are important in science and technology. Examples include biological fluids in membranes, liquids trapped in porous rocks, and thin-film materials used in high-resolution patterning technologies. However, few reliable rules exist to predict how the properties of materials will be affected by thin-film confinement. We have recently shown that the potential energy landscape formalism can be used to study, by both theory [1] and simulation [2], how the behavior of thin-film materials depends on sample dimensions and film-substrate interactions. Our landscape-based mean-field theory [1] can be used to study both the thermodynamic properties and the ideal glass transition of thin films. It predicts that, in the case of neutral or repulsive walls, the ideal glass transition temperature is lowered by decreasing film thickness. This is in qualitative agreement with experimental trends for the kinetic glass transition in confined fluids. Landscape-based approaches are also valuable for understanding the structural and mechanical properties of thin-film glasses. We demonstrate how the concept of an "equation of state of the energy landscape" [3] can be generalized to thin films [1, 2], where it gives insights into potential molecular mechanisms of tensile strength. [1] T. M. Truskett and V. Ganesan, J. Chem. Phys. 119, 1897-1900(2003); J. Mittal, P. Shah and T. M. Truskett, to be submitted to Langmuir. [2] P. Shah and T. M. Truskett, to be submitted to J. Phys. Chem. B. [3] S. Sastry, P. G. Debenedetti and F. H. Stillinger, Phys. Rev. E 56, 5533 (1997)

  19. Self-organized criticality and color vision: A guide to water-protein landscape evolution

    Science.gov (United States)

    Phillips, J. C.

    2013-02-01

    We focus here on the scaling properties of small interspecies differences between red cone opsin transmembrane proteins, using a hydropathic elastic roughening tool previously applied to the rhodopsin rod transmembrane proteins. This tool is based on a non-Euclidean hydropathic metric realistically rooted in the atomic coordinates of 5526 protein segments, which thereby encapsulates universal non-Euclidean long-range differential geometrical features of water films enveloping globular proteins in the Protein Data Bank. Whereas the rhodopsin blue rod water films are smoothest in humans, the red cone opsins’ water films are optimized for smoothness in cats and elephants, consistent with protein species landscapes that evolve differently in different contexts. We also analyze red cone opsins in the chromatophore-containing family of chameleons, snakes, zebrafish and goldfish, where short- and long-range (BLAST and hydropathic) amino acid (aa) correlations are found with values as large as 97%-99%. We use hydropathic aa optimization to estimate the maximum number Nmax of color shades that the human eye can discriminate, and obtain 106

  20. Multiple coupled landscapes and non-adiabatic dynamics with applications to self-activating genes.

    Science.gov (United States)

    Chen, Cong; Zhang, Kun; Feng, Haidong; Sasai, Masaki; Wang, Jin

    2015-11-21

    Many physical, chemical and biochemical systems (e.g. electronic dynamics and gene regulatory networks) are governed by continuous stochastic processes (e.g. electron dynamics on a particular electronic energy surface and protein (gene product) synthesis) coupled with discrete processes (e.g. hopping among different electronic energy surfaces and on and off switching of genes). One can also think of the underlying dynamics as the continuous motion on a particular landscape and discrete hoppings among different landscapes. The main difference of such systems from the intra-landscape dynamics alone is the emergence of the timescale involved in transitions among different landscapes in addition to the timescale involved in a particular landscape. The adiabatic limit when inter-landscape hoppings are fast compared to continuous intra-landscape dynamics has been studied both analytically and numerically, but the analytical treatment of the non-adiabatic regime where the inter-landscape hoppings are slow or comparable to continuous intra-landscape dynamics remains challenging. In this study, we show that there exists mathematical mapping of the dynamics on 2(N) discretely coupled N continuous dimensional landscapes onto one single landscape in 2N dimensional extended continuous space. On this 2N dimensional landscape, eddy current emerges as a sign of non-equilibrium non-adiabatic dynamics and plays an important role in system evolution. Many interesting physical effects such as the enhancement of fluctuations, irreversibility, dissipation and optimal kinetics emerge due to non-adiabaticity manifested by the eddy current illustrated for an N = 1 self-activator. We further generalize our theory to the N-gene network with multiple binding sites and multiple synthesis rates for discretely coupled non-equilibrium stochastic physical and biological systems.

  1. Protein energy malnutrition.

    Science.gov (United States)

    Grover, Zubin; Ee, Looi C

    2009-10-01

    Protein energy malnutrition (PEM) is a common problem worldwide and occurs in both developing and industrialized nations. In the developing world, it is frequently a result of socioeconomic, political, or environmental factors. In contrast, protein energy malnutrition in the developed world usually occurs in the context of chronic disease. There remains much variation in the criteria used to define malnutrition, with each method having its own limitations. Early recognition, prompt management, and robust follow up are critical for best outcomes in preventing and treating PEM.

  2. Multivariable extrapolation of grand canonical free energy landscapes

    Science.gov (United States)

    Mahynski, Nathan A.; Errington, Jeffrey R.; Shen, Vincent K.

    2017-12-01

    We derive an approach for extrapolating the free energy landscape of multicomponent systems in the grand canonical ensemble, obtained from flat-histogram Monte Carlo simulations, from one set of temperature and chemical potentials to another. This is accomplished by expanding the landscape in a Taylor series at each value of the order parameter which defines its macrostate phase space. The coefficients in each Taylor polynomial are known exactly from fluctuation formulas, which may be computed by measuring the appropriate moments of extensive variables that fluctuate in this ensemble. Here we derive the expressions necessary to define these coefficients up to arbitrary order. In principle, this enables a single flat-histogram simulation to provide complete thermodynamic information over a broad range of temperatures and chemical potentials. Using this, we also show how to combine a small number of simulations, each performed at different conditions, in a thermodynamically consistent fashion to accurately compute properties at arbitrary temperatures and chemical potentials. This method may significantly increase the computational efficiency of biased grand canonical Monte Carlo simulations, especially for multicomponent mixtures. Although approximate, this approach is amenable to high-throughput and data-intensive investigations where it is preferable to have a large quantity of reasonably accurate simulation data, rather than a smaller amount with a higher accuracy.

  3. Linking habitat selection to fitness-related traits in herbivores: the role of the energy landscape

    Science.gov (United States)

    Ryan A. Long; R. T. Bowyer; Warren P. Porter; Paul Mathewson; Kevin L. Monteith; Scott L. Findholt; Brian L. Dick; John G. Kie

    2016-01-01

    Animals may partially overcome environmental constraints on fitness by behaviorally adjusting their exposure to costs and supplies of energy. Few studies, however, have linked spatiotemporal variation in the energy landscape to behaviorally mediated measures of performance that ostensibly influence individual fitness. We hypothesized that strength of selection by North...

  4. A Tale of Two Regions: Landscape Ecological Planning for Shale Gas Energy Futures

    Science.gov (United States)

    Murtha, T., Jr.; Schroth, O.; Orland, B.; Goldberg, L.; Mazurczyk, T.

    2015-12-01

    As we increasingly embrace deep shale gas deposits to meet global energy demands new and dispersed local and regional policy and planning challenges emerge. Even in regions with long histories of energy extraction, such as coal, shale gas and the infrastructure needed to produce the gas and transport it to market offers uniquely complex transformations in land use and landcover not previously experienced. These transformations are fast paced, dispersed and can overwhelm local and regional planning and regulatory processes. Coupled to these transformations is a structural confounding factor. While extraction and testing are carried out locally, regulation and decision-making is multilayered, often influenced by national and international factors. Using a geodesign framework, this paper applies a set of geospatial landscape ecological planning tools in two shale gas settings. First, we describe and detail a series of ongoing studies and tools that we have developed for communities in the Marcellus Shale region of the eastern United States, specifically the northern tier of Pennsylvania. Second, we apply a subset of these tools to potential gas development areas of the Fylde region in Lancashire, United Kingdom. For the past five years we have tested, applied and refined a set of place based and data driven geospatial models for forecasting, envisioning, analyzing and evaluating shale gas activities in northern Pennsylvania. These models are continuously compared to important landscape ecological planning challenges and priorities in the region, e.g. visual and cultural resource preservation. Adapting and applying these tools to a different landscape allow us to not only isolate and define important regulatory and policy exigencies in each specific setting, but also to develop and refine these models for broader application. As we continue to explore increasingly complex energy solutions globally, we need an equally complex comparative set of landscape ecological

  5. Associations of Dietary Protein and Energy Intakes With Protein-Energy Wasting Syndrome in Hemodialysis Patients.

    Science.gov (United States)

    Beddhu, Srinivasan; Wei, Guo; Chen, Xiaorui; Boucher, Robert; Kiani, Rabia; Raj, Dominic; Chonchol, Michel; Greene, Tom; Murtaugh, Maureen A

    2017-09-01

    The associations of dietary protein and/or energy intakes with protein or energy wasting in patients on maintenance hemodialysis are controversial. We examined these in the Hemodialysis (HEMO) Study. In 1487 participants in the HEMO Study, baseline dietary protein intake (grams per kilogram per day) and dietary energy intake (kilocalories per kilograms per day) were related to the presence of the protein-energy wasting (PEW) syndrome at month 12 (defined as the presence of at least 1 criteria in 2 of the 3 categories of low serum chemistry, low body mass, and low muscle mass) in logistic regression models. In additional separate models, protein intake estimated from equilibrated normalized protein catabolic rate (enPCR) was also related to the PEW syndrome. Compared with the lowest quartile, the highest quartile of baseline dietary protein intake was paradoxically associated with increased risk of the PEW syndrome at month 12 (odds ratio [OR]: 4.11; 95% confidence interval [CI]: 2.79-6.05). This relationship was completely attenuated (OR: 1.35; 95% CI: 0.88-2.06) with adjustment for baseline body weight, which suggested mathematical coupling. Results were similar for dietary energy intake. Compared with the lowest quartile of baseline enPCR, the highest quartile was not associated with the PEW syndrome at 12 months (OR: 0.78; 95% CI: 0.54-1.12). These data do not support the use of dietary protein intake or dietary energy intake criteria in the definition of the PEW syndrome in patients on maintenance hemodialysis.

  6. A data-driven analysis of energy balance closure across FLUXNET research sites: The role of landscape scale heterogeneity

    DEFF Research Database (Denmark)

    Stoy, Paul C.; Mauder, Matthias; Foken, Thomas

    2013-01-01

    approached 1. These results suggest that landscape-level heterogeneity in vegetation and topography cannot be ignored as a contributor to incomplete energy balance closure at the flux network level, although net radiation measurements, biological energy assimilation, unmeasured storage terms......The energy balance at most surface-atmosphere flux research sites remains unclosed. The mechanisms underlying the discrepancy between measured energy inputs and outputs across the global FLUXNET tower network are still under debate. Recent reviews have identified exchange processes and turbulent...... motions at large spatial and temporal scales in heterogeneous landscapes as the primary cause of the lack of energy balance closure at some intensively-researched sites, while unmeasured storage terms cannot be ruled out as a dominant contributor to the lack of energy balance closure at many other sites...

  7. Free energy landscape and molecular pathways of gas hydrate nucleation

    Energy Technology Data Exchange (ETDEWEB)

    Bi, Yuanfei; Porras, Anna; Li, Tianshu, E-mail: tsli@gwu.edu [Department of Civil and Environmental Engineering, George Washington University, Washington DC 20052 (United States)

    2016-12-07

    Despite the significance of gas hydrates in diverse areas, a quantitative knowledge of hydrate formation at a molecular level is missing. The impediment to acquiring this understanding is primarily attributed to the stochastic nature and ultra-fine scales of nucleation events, posing a great challenge for both experiment and simulation to explore hydrate nucleation. Here we employ advanced molecular simulation methods, including forward flux sampling (FFS), p{sub B} histogram analysis, and backward flux sampling, to overcome the limit of direct molecular simulation for exploring both the free energy landscape and molecular pathways of hydrate nucleation. First we test the half-cage order parameter (H-COP) which we developed for driving FFS, through conducting the p{sub B} histogram analysis. Our results indeed show that H-COP describes well the reaction coordinates of hydrate nucleation. Through the verified order parameter, we then directly compute the free energy landscape for hydrate nucleation by combining both forward and backward flux sampling. The calculated stationary distribution density, which is obtained independently of nucleation theory, is found to fit well against the classical nucleation theory (CNT). Subsequent analysis of the obtained large ensemble of hydrate nucleation trajectories show that although on average, hydrate formation is facilitated by a two-step like mechanism involving a gradual transition from an amorphous to a crystalline structure, there also exist nucleation pathways where hydrate crystallizes directly, without going through the amorphous stage. The CNT-like free energy profile and the structural diversity suggest the existence of multiple active transition pathways for hydrate nucleation, and possibly also imply the near degeneracy in their free energy profiles among different pathways. Our results thus bring a new perspective to the long standing question of how hydrates crystallize.

  8. Free energy landscape and molecular pathways of gas hydrate nucleation

    International Nuclear Information System (INIS)

    Bi, Yuanfei; Porras, Anna; Li, Tianshu

    2016-01-01

    Despite the significance of gas hydrates in diverse areas, a quantitative knowledge of hydrate formation at a molecular level is missing. The impediment to acquiring this understanding is primarily attributed to the stochastic nature and ultra-fine scales of nucleation events, posing a great challenge for both experiment and simulation to explore hydrate nucleation. Here we employ advanced molecular simulation methods, including forward flux sampling (FFS), p B histogram analysis, and backward flux sampling, to overcome the limit of direct molecular simulation for exploring both the free energy landscape and molecular pathways of hydrate nucleation. First we test the half-cage order parameter (H-COP) which we developed for driving FFS, through conducting the p B histogram analysis. Our results indeed show that H-COP describes well the reaction coordinates of hydrate nucleation. Through the verified order parameter, we then directly compute the free energy landscape for hydrate nucleation by combining both forward and backward flux sampling. The calculated stationary distribution density, which is obtained independently of nucleation theory, is found to fit well against the classical nucleation theory (CNT). Subsequent analysis of the obtained large ensemble of hydrate nucleation trajectories show that although on average, hydrate formation is facilitated by a two-step like mechanism involving a gradual transition from an amorphous to a crystalline structure, there also exist nucleation pathways where hydrate crystallizes directly, without going through the amorphous stage. The CNT-like free energy profile and the structural diversity suggest the existence of multiple active transition pathways for hydrate nucleation, and possibly also imply the near degeneracy in their free energy profiles among different pathways. Our results thus bring a new perspective to the long standing question of how hydrates crystallize.

  9. Free energy landscape and molecular pathways of gas hydrate nucleation.

    Science.gov (United States)

    Bi, Yuanfei; Porras, Anna; Li, Tianshu

    2016-12-07

    Despite the significance of gas hydrates in diverse areas, a quantitative knowledge of hydrate formation at a molecular level is missing. The impediment to acquiring this understanding is primarily attributed to the stochastic nature and ultra-fine scales of nucleation events, posing a great challenge for both experiment and simulation to explore hydrate nucleation. Here we employ advanced molecular simulation methods, including forward flux sampling (FFS), p B histogram analysis, and backward flux sampling, to overcome the limit of direct molecular simulation for exploring both the free energy landscape and molecular pathways of hydrate nucleation. First we test the half-cage order parameter (H-COP) which we developed for driving FFS, through conducting the p B histogram analysis. Our results indeed show that H-COP describes well the reaction coordinates of hydrate nucleation. Through the verified order parameter, we then directly compute the free energy landscape for hydrate nucleation by combining both forward and backward flux sampling. The calculated stationary distribution density, which is obtained independently of nucleation theory, is found to fit well against the classical nucleation theory (CNT). Subsequent analysis of the obtained large ensemble of hydrate nucleation trajectories show that although on average, hydrate formation is facilitated by a two-step like mechanism involving a gradual transition from an amorphous to a crystalline structure, there also exist nucleation pathways where hydrate crystallizes directly, without going through the amorphous stage. The CNT-like free energy profile and the structural diversity suggest the existence of multiple active transition pathways for hydrate nucleation, and possibly also imply the near degeneracy in their free energy profiles among different pathways. Our results thus bring a new perspective to the long standing question of how hydrates crystallize.

  10. Is the fenamate group a polymorphophore?: contrasting the crystal energy landscapes of fenamic and tolfenamic acids

    NARCIS (Netherlands)

    Uzoh, O.G.; Cruz-Cabeza, A.J.; Price, S. L.

    2012-01-01

    The concept of a polymorphophore was investigated by contrasting the crystal energy landscapes of monomorphic fenamic acid (2-(phenylamino)-benzoic acid, FA) and one of its highly polymorphic derivatives, tolfenamic acid (2-[(3-chloro-2-methylphenyl)amino]-benzoic acid, TA). The crystal energy

  11. Strong field-matching effects in superconducting YBa2Cu3O7-δ films with vortex energy landscapes engineered via masked ion irradiation

    Science.gov (United States)

    Swiecicki, I.; Ulysse, C.; Wolf, T.; Bernard, R.; Bergeal, N.; Briatico, J.; Faini, G.; Lesueur, J.; Villegas, Javier E.

    2012-06-01

    We have developed a masked ion irradiation technique to engineer the energy landscape for vortices in oxide superconductors. This approach associates the possibility to design the landscape geometry at the nanoscale with the unique capability to adjust the depth of the energy wells for vortices. This enabled us to unveil the key role of vortex channeling in modulating the amplitude of the field matching effects with the artificial energy landscape, and to make the latter govern flux dynamics over an unusually wide range of temperatures and applied fields for high-temperature superconducting films.

  12. The mechanisms for filling carbon nanotubes with molten salts: carbon nanotubes as energy landscape filters

    International Nuclear Information System (INIS)

    Bishop, Clare L; Wilson, Mark

    2009-01-01

    The mechanisms for filling carbon nanotubes with molten salts are investigated using molecular dynamics computer simulation. Inorganic nanotubular structures, whose morphologies can be rationalized in terms of the folding, or the removal of sections from, planes of square nets are found to form. The formation mechanisms are found to follow a 'chain-by-chain' motif in which the structures build systematically from charge neutral M-X-M-Xc chains. The formation mechanisms are rationalized in terms of the ion-ion interactions (intra-chain and inter-chain terms). In addition, the mechanisms of filling are discussed in terms of a 'hopping' between basins on the underlying energy landscape. The role of the carbon nanotube as an energy landscape filter is discussed.

  13. Protein leverage effects of beef protein on energy intake in humans.

    Science.gov (United States)

    Martens, Eveline A; Tan, Sze-Yen; Dunlop, Mandy V; Mattes, Richard D; Westerterp-Plantenga, Margriet S

    2014-06-01

    The protein leverage hypothesis requires specific evidence that protein intake is regulated more strongly than energy intake. The objective was to determine ad libitum energy intake, body weight changes, appetite profile, and nitrogen balance in response to 3 diets with different protein-to-carbohydrate + fat ratios over 12 consecutive days, with beef as a source of protein. A 3-arm, 12-d randomized crossover study was performed in 30 men and 28 women [mean ± SD age: 33 ± 16 y; body mass index (in kg/m²): 24.4 ± 4.0] with the use of diets containing 5%, 15%, and 30% of energy (En%) from protein, predominantly from beef. Energy intake was significantly lower in the 30En%-protein condition (8.73 ± 1.93 MJ/d) than in the 5En%-protein (9.48 ± 1.67 MJ/d) and 15En%-protein (9.30 ± 1.62 MJ/d) conditions (P = 0.001), stemming largely from lower energy intake during meals (P = 0.001). Hunger (P = 0.001) and desire to eat (P = 0.001) ratings were higher and fullness ratings were lower (P = 0.001) in the 5En%-protein condition than in the 15En%-protein and 30En%-protein conditions. Nitrogen excretion was lower in the 5En%-protein condition (4.7 ± 1.5 g/24 h; P = 0.001) and was higher in the 30En%-protein condition (15.3 ± 8.7 g/24 h; P = 0.001) compared with the 15En%-protein condition (10.0 ± 5.2 g/24 h). Nitrogen balance was maintained in the 5En%-protein condition and was positive in the 15En%- and 30En%-protein conditions (P = 0.001). Complete protein leverage did not occur because subjects did not consume to a common protein amount at the expense of energy balance. Individuals did underconsume relative to energy requirements from high-protein diets. The lack of support for protein leverage effects on a low-protein diet may stem from the fact that protein intake was sufficient to maintain nitrogen balance over the 12-d trial. © 2014 American Society for Nutrition.

  14. Control over Structure and Function of Peptide Amphiphile Supramolecular Assemblies through Molecular Design and Energy Landscapes

    Science.gov (United States)

    Tantakitti, Faifan

    a controlled local release of the soluble growth factor bone morphogenetic protein 4 (BMP-4) was realized from the particle's core composed of cross-linked alginate. The alginate-core and PA-shell microparticles were found to allow independent tuning of the bioactivity of a PA and a release of the growth factor for specific signaling to cells. Using microcarriers which encapsulated BMP-4 and coated with RGDS PA nanofibers, it was shown that a control over spatial distribution, proliferation, and osteogenic differentiation of premyoblastic cells on the surface of microcarriers can be effectively achieved. Finally, in drastic contrast to the traditional approach to material development based on altering molecular structure, chapter 4 presents the energy landscapes in which supramolecular assemblies of unique architecture exist in different thermodynamic wells. Experimental results and calculations revealed that the energy landscapes are rooted in competing interactions between PA monomers, namely beta-sheet hydrogen bonds and repulsion among charged groups. Switching off or on the repulsive electrostatic interactions by changing the ionic strength promoted or suppressed the dominant ?-sheet hydrogen bonding interactions respectively. However, the dominant forces can prevail if the assemblies are above a certain size and thereby can exist in a kinetically trapped state. Preparative pathways involving dilution, annealing, and addition of salt were investigated in which the structures belonging to different energy states could be accessed and demonstrated that these energy landscapes involving competitive interactions was applicable not only to PA systems but also to a non-peptide supramolecular system based on pi-orbital overlaps as the dominant attraction among molecules and electrostatic repulsion. In chapter 5, structure and biological function relationships of long or short PA nanofibers are reported, and such fibers were prepared from identical monomers based on

  15. Temporal disconnectivity of the energy landscape in glassy systems

    Science.gov (United States)

    Lempesis, Nikolaos; Boulougouris, Georgios C.; Theodorou, Doros N.

    2013-03-01

    An alternative graphical representation of the potential energy landscape (PEL) has been developed and applied to a binary Lennard-Jones glassy system, providing insight into the unique topology of the system's potential energy hypersurface. With the help of this representation one is able to monitor the different explored basins of the PEL, as well as how - and mainly when - subsets of basins communicate with each other via transitions in such a way that details of the prior temporal history have been erased, i.e., local equilibration between the basins in each subset has been achieved. In this way, apart from detailed information about the structure of the PEL, the system's temporal evolution on the PEL is described. In order to gather all necessary information about the identities of two or more basins that are connected with each other, we consider two different approaches. The first one is based on consideration of the time needed for two basins to mutually equilibrate their populations according to the transition rate between them, in the absence of any effect induced by the rest of the landscape. The second approach is based on an analytical solution of the master equation that explicitly takes into account the entire explored landscape. It is shown that both approaches lead to the same result concerning the topology of the PEL and dynamical evolution on it. Moreover, a "temporal disconnectivity graph" is introduced to represent a lumped system stemming from the initial one. The lumped system is obtained via a specially designed algorithm [N. Lempesis, D. G. Tsalikis, G. C. Boulougouris, and D. N. Theodorou, J. Chem. Phys. 135, 204507 (2011), 10.1063/1.3663207]. The temporal disconnectivity graph provides useful information about both the lumped and the initial systems, including the definition of "metabasins" as collections of basins that communicate with each other via transitions that are fast relative to the observation time. Finally, the two examined

  16. Energy landscapes shape microbial communities in hydrothermal systems on the Arctic Mid-Ocean Ridge.

    Science.gov (United States)

    Dahle, Håkon; Økland, Ingeborg; Thorseth, Ingunn H; Pederesen, Rolf B; Steen, Ida H

    2015-07-01

    Methods developed in geochemical modelling combined with recent advances in molecular microbial ecology provide new opportunities to explore how microbial communities are shaped by their chemical surroundings. Here, we present a framework for analyses of how chemical energy availability shape chemotrophic microbial communities in hydrothermal systems through an investigation of two geochemically different basalt-hosted hydrothermal systems on the Arctic Mid-Ocean Ridge: the Soria Moria Vent field (SMVF) and the Loki's Castle Vent Field (LCVF). Chemical energy landscapes were evaluated through modelling of the Gibbs energy from selected redox reactions under different mixing ratios between seawater and hydrothermal fluids. Our models indicate that the sediment-influenced LCVF has a much higher potential for both anaerobic and aerobic methane oxidation, as well as aerobic ammonium and hydrogen oxidation, than the SMVF. The modelled energy landscapes were used to develop microbial community composition models, which were compared with community compositions in environmental samples inside or on the exterior of hydrothermal chimneys, as assessed by pyrosequencing of partial 16S rRNA genes. We show that modelled microbial communities based solely on thermodynamic considerations can have a high predictive power and provide a framework for analyses of the link between energy availability and microbial community composition.

  17. The effect of tensile stress on the conformational free energy landscape of disulfide bonds.

    Directory of Open Access Journals (Sweden)

    Padmesh Anjukandi

    Full Text Available Disulfide bridges are no longer considered to merely stabilize protein structure, but are increasingly recognized to play a functional role in many regulatory biomolecular processes. Recent studies have uncovered that the redox activity of native disulfides depends on their C-C-S-S dihedrals, χ2 and χ'2. Moreover, the interplay of chemical reactivity and mechanical stress of disulfide switches has been recently elucidated using force-clamp spectroscopy and computer simulation. The χ2 and χ'2 angles have been found to change from conformations that are open to nucleophilic attack to sterically hindered, so-called closed states upon exerting tensile stress. In view of the growing evidence of the importance of C-C-S-S dihedrals in tuning the reactivity of disulfides, here we present a systematic study of the conformational diversity of disulfides as a function of tensile stress. With the help of force-clamp metadynamics simulations, we show that tensile stress brings about a large stabilization of the closed conformers, thereby giving rise to drastic changes in the conformational free energy landscape of disulfides. Statistical analysis shows that native TDi, DO and interchain Ig protein disulfides prefer open conformations, whereas the intrachain disulfide bridges in Ig proteins favor closed conformations. Correlating mechanical stress with the distance between the two a-carbons of the disulfide moiety reveals that the strain of intrachain Ig protein disulfides corresponds to a mechanical activation of about 100 pN. Such mechanical activation leads to a severalfold increase of the rate of the elementary redox S(N2 reaction step. All these findings constitute a step forward towards achieving a full understanding of functional disulfides.

  18. The potential energy landscape in the Lennard-Jones binary mixture model

    International Nuclear Information System (INIS)

    Sampoli, M; Benassi, P; Eramo, R; Angelani, L; Ruocco, G

    2003-01-01

    The potential energy landscape in the Kob-Andersen Lennard-Jones binary mixture model has been studied carefully from the liquid down to the supercooled regime, from T = 2 down to 0.46. One thousand independent configurations along the time evolution locus have been examined at each temperature investigated. From the starting configuration, we searched for the nearest saddle (or quasi-saddle) and minimum of the potential energy. The vibrational densities of states for the starting and the two derived configurations have been evaluated. Besides the number of negative eigenvalues of the saddles other quantities show some signature of the approach of the dynamical arrest temperature

  19. [Protein-energy malnutrition in clinical practice].

    Science.gov (United States)

    Necheva, G I; Druk, I V; Lialiukova, E A

    2013-01-01

    The analysis of the reasons and mechanisms of development of an protein-energy malnutrition, communication of fetal pathology and development of an protein-energy malnutrition at mature age is submitted. Systemic character of a syndrome is marked out. Importance of a problem of an protein-energy malnutrition at patients with a dysplasia of a connecting tissue is bound to high prevalence of a syndrome at this pathology.

  20. Dissecting Protein Configurational Entropy into Conformational and Vibrational Contributions.

    Science.gov (United States)

    Chong, Song-Ho; Ham, Sihyun

    2015-10-01

    Quantifying how the rugged nature of the underlying free-energy landscape determines the entropic cost a protein must incur upon folding and ligand binding is a challenging problem. Here, we present a novel computational approach that dissects the protein configurational entropy on the basis of the classification of protein dynamics on the landscape into two separate components: short-term vibrational dynamics related to individual free-energy wells and long-term conformational dynamics associated with transitions between wells. We apply this method to separate the configurational entropy of the protein villin headpiece subdomain into its conformational and vibrational components. We find that the change in configurational entropy upon folding is dominated by the conformational entropy despite the fact that the magnitude of the vibrational entropy is the significantly larger component in each of the folded and unfolded states, which is in accord with the previous empirical estimations. The straightforward applicability of our method to unfolded proteins promises a wide range of applications, including those related to intrinsically disordered proteins.

  1. Landscape of Future Accelerators at the Energy and Intensity Frontier

    Energy Technology Data Exchange (ETDEWEB)

    Syphers, M. J. [Northern Illinois U.; Chattopadhyay, S. [Northern Illinois U.

    2016-11-21

    An overview is provided of the currently envisaged landscape of charged particle accelerators at the energy and intensity frontiers to explore particle physics beyond the standard model via 1-100 TeV-scale lepton and hadron colliders and multi-Megawatt proton accelerators for short- and long- baseline neutrino experiments. The particle beam physics, associated technological challenges and progress to date for these accelerator facilities (LHC, HL-LHC, future 100 TeV p-p colliders, Tev-scale linear and circular electron-positron colliders, high intensity proton accelerator complex PIP-II for DUNE and future upgrade to PIP-III) are outlined. Potential and prospects for advanced “nonlinear dynamic techniques” at the multi-MW level intensity frontier and advanced “plasma- wakefield-based techniques” at the TeV-scale energy frontier and are also described.

  2. Impacts on the environment and landscape of new energy productions on farm parcels and buildings, Final report

    International Nuclear Information System (INIS)

    Pointereau, Ph.; Bochu, J.L.; Couturier, Ch.; Coulon, F.; Arnal, A.; Giorgis, S.

    2009-01-01

    This study aims at identifying positive and negative impacts of new energy productions implemented in farms on the environment (water, soil, biodiversity, space occupancy) and on landscapes, and at proposing techniques and regulations to strengthen positive consequences and to limit possible problems created by these energy productions. The considered productions are: trees apart from forest (hedges and copses), new farm energetic crops (Miscanthus for example), solar equipment (photovoltaic mounted on buildings or on ground, solar hot water and solar dryers), biogas production equipment, hydraulic micro-plants. The authors addressed the following environmental impacts: water (in quantity and quality), soils (quality, erosion risks), biodiversity, space occupancy (with respect to other activities), and landscape

  3. Gentlest ascent dynamics for calculating first excited state and exploring energy landscape of Kohn-Sham density functionals.

    Science.gov (United States)

    Li, Chen; Lu, Jianfeng; Yang, Weitao

    2015-12-14

    We develop the gentlest ascent dynamics for Kohn-Sham density functional theory to search for the index-1 saddle points on the energy landscape of the Kohn-Sham density functionals. These stationary solutions correspond to excited states in the ground state functionals. As shown by various examples, the first excited states of many chemical systems are given by these index-1 saddle points. Our novel approach provides an alternative, more robust way to obtain these excited states, compared with the widely used ΔSCF approach. The method can be easily generalized to target higher index saddle points. Our results also reveal the physical interest and relevance of studying the Kohn-Sham energy landscape.

  4. Multifunctional energy landscape for a DNA G-quadruplex: An evolved molecular switch

    Science.gov (United States)

    Cragnolini, Tristan; Chakraborty, Debayan; Šponer, Jiří; Derreumaux, Philippe; Pasquali, Samuela; Wales, David J.

    2017-10-01

    We explore the energy landscape for a four-fold telomere repeat, obtaining interconversion pathways between six experimentally characterised G-quadruplex topologies. The results reveal a multi-funnel system, with a variety of intermediate configurations and misfolded states. This organisation is identified with the intrinsically multi-functional nature of the system, suggesting a new paradigm for the classification of such biomolecules and clarifying issues regarding apparently conflicting experimental results.

  5. A Community Landscape Model of Pro-Environmental Behavior: The Effects of Landscape and Community Interaction on Residential Energy Behaviors in Two Pennsylvania Towns

    Science.gov (United States)

    Mainzer, Stephen P.

    We are using more energy every year. Between 2001 and 2011, Pennsylvania residential electricity sales increased by two and a half times the number of new customers, accounting for almost one third of the state's total electricity consumption. Our ability to meet demand by acquiring new energy sources faces several challenges. Confusion surrounds the physical and economic accessibility of remaining fossil fuel sources. Immense land use requirements and subsequent environmental impacts challenge a total shift to renewable energy sources. The laws of thermodynamics limit the potential for new technology to efficiently convert raw energy to consumable sources. As a result, any rational strategy to meet future energy demands must involve conservation. Conservation is a pro-environmental behavior, an act intended to benefit the environment surrounding a person. I posit that a transdisciplinary model, the community landscape model of the pro-environmental behavior, unifies the conceptually analogous - yet disparate - fields of landscape, community, and behavior towards explaining residential energy conservation actions. Specifically, the study attempted to describe links between the physical environment, social environment, and conservation behaviors through a mixed-method framework. Two Pennsylvania townships - Spring and East Buffalo townships - were selected from an analysis of housing, electricity consumption, and land cover trends. Key informants from both townships informed the design of a survey instrument that captured the utility consumption, residential conservation actions, energy and environmental values, types and levels of community engagement, perceived barriers, and socio-demographic information from 107 randomly selected households. A mixed-method analysis produced evidence that place-based values and intention to participate in the community were significantly linked to lower utility consumption in households. People who cared deeply about their town

  6. The energy landscape of glassy dynamics on the amorphous hafnium diboride surface

    Science.gov (United States)

    Nguyen, Duc; Mallek, Justin; Cloud, Andrew N.; Abelson, John R.; Girolami, Gregory S.; Lyding, Joseph; Gruebele, Martin

    2014-11-01

    Direct visualization of the dynamics of structural glasses and amorphous solids on the sub-nanometer scale provides rich information unavailable from bulk or conventional single molecule techniques. We study the surface of hafnium diboride, a conductive ultrahigh temperature ceramic material that can be grown in amorphous films. Our scanning tunneling movies have a second-to-hour dynamic range and single-point current measurements extend that to the millisecond-to-minute time scale. On the a-HfB2 glass surface, two-state hopping of 1-2 nm diameter cooperatively rearranging regions or "clusters" occurs from sub-milliseconds to hours. We characterize individual clusters in detail through high-resolution (single cluster vertical displacements, we can reconstruct the local free energy landscape of individual clusters, complete with activation barrier height, a reaction coordinate in nanometers, and the shape of the free energy landscape basins between which hopping occurs. The experimental images are consistent with the compact shape of α-relaxors predicted by random first order transition theory, whereas the rapid hopping rate, even taking less confined motion at the surface into account, is consistent with β-relaxations. We make a proposal of how "mixed" features can show up in surface dynamics of glasses.

  7. Probing the energy landscape of alanine dipeptide and decalanine using temperature as a tunable parameter in molecular dynamics

    International Nuclear Information System (INIS)

    Chatterjee, A; Bhattacharya, S

    2016-01-01

    We perform several molecular dynamics (MD) calculations of solvated alanine dipeptide and decalanine in vacuum with temperature as a tunable parameter and in the process, generate Markov state models (MSMs) at each temperature. An interesting observation that the kinetic rates appear to obey the Arrhenius rate law allows us to predict the dynamics of alanine dipeptide at 300 K at the microsecond timescales using the nanoseconds long high temperature calculations without actually performing MD simulations at 300 K. We conclude that the energy landscape of alanine dipeptide contains superbasins deeper than k B T and determine the energy barriers associated with the moves from the Arrhenius rate expression. Similar insights regarding the energy landscape associated with folding/unfolding pathways of a deca-alanine molecule are obtained using kinetic rates calculated at different temperatures. (paper)

  8. Exploring the energy landscape of biopolymers using single molecule force spectroscopy and molecular simulations

    OpenAIRE

    Hyeon, Changbong

    2010-01-01

    In recent years, single molecule force techniques have opened a new avenue to decipher the folding landscapes of biopolymers by allowing us to watch and manipulate the dynamics of individual proteins and nucleic acids. In single molecule force experiments, quantitative analyses of measurements employing sound theoretical models and molecular simulations play central role more than any other field. With a brief description of basic theories for force mechanics and molecular simulation techniqu...

  9. Elucidation of the conformational free energy landscape in H.pylori LuxS and its implications to catalysis

    Directory of Open Access Journals (Sweden)

    Bhattacharyya Moitrayee

    2010-08-01

    Full Text Available Abstract Background One of the major challenges in understanding enzyme catalysis is to identify the different conformations and their populations at detailed molecular level in response to ligand binding/environment. A detail description of the ligand induced conformational changes provides meaningful insights into the mechanism of action of enzymes and thus its function. Results In this study, we have explored the ligand induced conformational changes in H.pylori LuxS and the associated mechanistic features. LuxS, a dimeric protein, produces the precursor (4,5-dihydroxy-2,3-pentanedione for autoinducer-2 production which is a signalling molecule for bacterial quorum sensing. We have performed molecular dynamics simulations on H.pylori LuxS in its various ligand bound forms and analyzed the simulation trajectories using various techniques including the structure network analysis, free energy evaluation and water dynamics at the active site. The results bring out the mechanistic details such as co-operativity and asymmetry between the two subunits, subtle changes in the conformation as a response to the binding of active and inactive forms of ligands and the population distribution of different conformations in equilibrium. These investigations have enabled us to probe the free energy landscape and identify the corresponding conformations in terms of network parameters. In addition, we have also elucidated the variations in the dynamics of water co-ordination to the Zn2+ ion in LuxS and its relation to the rigidity at the active sites. Conclusions In this article, we provide details of a novel method for the identification of conformational changes in the different ligand bound states of the protein, evaluation of ligand-induced free energy changes and the biological relevance of our results in the context of LuxS structure-function. The methodology outlined here is highly generalized to illuminate the linkage between structure and function in

  10. Investigating energy-based pool structure selection in the structure ensemble modeling with experimental distance constraints: The example from a multidomain protein Pub1.

    Science.gov (United States)

    Zhu, Guanhua; Liu, Wei; Bao, Chenglong; Tong, Dudu; Ji, Hui; Shen, Zuowei; Yang, Daiwen; Lu, Lanyuan

    2018-05-01

    The structural variations of multidomain proteins with flexible parts mediate many biological processes, and a structure ensemble can be determined by selecting a weighted combination of representative structures from a simulated structure pool, producing the best fit to experimental constraints such as interatomic distance. In this study, a hybrid structure-based and physics-based atomistic force field with an efficient sampling strategy is adopted to simulate a model di-domain protein against experimental paramagnetic relaxation enhancement (PRE) data that correspond to distance constraints. The molecular dynamics simulations produce a wide range of conformations depicted on a protein energy landscape. Subsequently, a conformational ensemble recovered with low-energy structures and the minimum-size restraint is identified in good agreement with experimental PRE rates, and the result is also supported by chemical shift perturbations and small-angle X-ray scattering data. It is illustrated that the regularizations of energy and ensemble-size prevent an arbitrary interpretation of protein conformations. Moreover, energy is found to serve as a critical control to refine the structure pool and prevent data overfitting, because the absence of energy regularization exposes ensemble construction to the noise from high-energy structures and causes a more ambiguous representation of protein conformations. Finally, we perform structure-ensemble optimizations with a topology-based structure pool, to enhance the understanding on the ensemble results from different sources of pool candidates. © 2018 Wiley Periodicals, Inc.

  11. Enhanced, targeted sampling of high-dimensional free-energy landscapes using variationally enhanced sampling, with an application to chignolin.

    Science.gov (United States)

    Shaffer, Patrick; Valsson, Omar; Parrinello, Michele

    2016-02-02

    The capabilities of molecular simulations have been greatly extended by a number of widely used enhanced sampling methods that facilitate escaping from metastable states and crossing large barriers. Despite these developments there are still many problems which remain out of reach for these methods which has led to a vigorous effort in this area. One of the most important problems that remains unsolved is sampling high-dimensional free-energy landscapes and systems that are not easily described by a small number of collective variables. In this work we demonstrate a new way to compute free-energy landscapes of high dimensionality based on the previously introduced variationally enhanced sampling, and we apply it to the miniprotein chignolin.

  12. Enhanced, targeted sampling of high-dimensional free-energy landscapes using variationally enhanced sampling, with an application to chignolin

    Science.gov (United States)

    Shaffer, Patrick; Valsson, Omar; Parrinello, Michele

    2016-01-01

    The capabilities of molecular simulations have been greatly extended by a number of widely used enhanced sampling methods that facilitate escaping from metastable states and crossing large barriers. Despite these developments there are still many problems which remain out of reach for these methods which has led to a vigorous effort in this area. One of the most important problems that remains unsolved is sampling high-dimensional free-energy landscapes and systems that are not easily described by a small number of collective variables. In this work we demonstrate a new way to compute free-energy landscapes of high dimensionality based on the previously introduced variationally enhanced sampling, and we apply it to the miniprotein chignolin. PMID:26787868

  13. Co-designing energy landscapes: Application of participatory mapping and geographic information systems in the exploration of low carbon futures

    NARCIS (Netherlands)

    Stremke, S.; Picchi, Paolo

    2017-01-01

    The chapter begins with a literature review of energy potential mapping, ecosystem services (ES) assessment and participatory mapping (PM). PM is a key technique to conduct tradeoff analysis while co-designing sustainable energy landscapes (SEL) with local communities. Stakeholders, among others,

  14. Conjugate gradient filtering of instantaneous normal modes, saddles on the energy landscape, and diffusion in liquids.

    Science.gov (United States)

    Chowdhary, J; Keyes, T

    2002-02-01

    Instantaneous normal modes (INM's) are calculated during a conjugate-gradient (CG) descent of the potential energy landscape, starting from an equilibrium configuration of a liquid or crystal. A small number (approximately equal to 4) of CG steps removes all the Im-omega modes in the crystal and leaves the liquid with diffusive Im-omega which accurately represent the self-diffusion constant D. Conjugate gradient filtering appears to be a promising method, applicable to any system, of obtaining diffusive modes and facilitating INM theory of D. The relation of the CG-step dependent INM quantities to the landscape and its saddles is discussed.

  15. Nutrition and protein energy homeostasis in elderly.

    Science.gov (United States)

    Boirie, Yves; Morio, Béatrice; Caumon, Elodie; Cano, Noël J

    2014-01-01

    Protein-energy homeostasis is a major determinant of healthy aging. Inadequate nutritional intakes and physical activity, together with endocrine disturbances are associated with of sarcopenia and frailty. Guidelines from scientific societies mainly address the quantitative aspects of protein and energy nutrition in elderly. Besides these quantitative aspects of protein load, perspective strategies to promote muscle protein synthesis and prevent sarcopenia include pulse feeding, the use of fast proteins and the addition of leucine or citrulline to dietary protein. An integrated management of sarcopenia, taking into account the determinants of muscle wasting, i.e. nutrition, physical activity, anabolic factors such as androgens, vitamin D and n-3 polyunsaturated fatty acids status, needs to be tested in the prevention and treatment of sarcopenia. The importance of physical activity, specifically resistance training, is emphasized, not only in order to facilitate muscle protein anabolism but also to increase appetite and food intake in elderly people at risk of malnutrition. According to present data, healthy nutrition in elderly should respect the guidelines for protein and energy requirement, privilege a Mediterranean way of alimentation, and be associated with a regular physical activity. Further issues relate to the identification of the genetics determinants of protein energy wasting in elderly. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. The importance of on-site evaluation for placing renewable energy in the landscape: A case study of the Búrfell wind farm (Iceland

    Directory of Open Access Journals (Sweden)

    Frantál Bohumil

    2017-12-01

    Full Text Available Using a case study of the Búrfell wind farm project, a large wind farm proposed in the Central Highlands of Iceland, the authors attempt to provide new insights into the factors shaping subjective landscape perceptions and attitudes to renewable energy developments, and into alternative methods that may be used for their assessment. The research was based on an on-site visit and actual experience of the place, investigated using a combination of mental mapping, the technique of the semantic differential and a questionnaire survey. The results show that participants visiting a landscape and using all sensory organs in combination with mental mapping, can reveal more important information than using only ‘laboratory’ methods with static photographs. The results suggest that the perception of landscape is highly subjective. Those perceiving the landscape as more open, homogenous, industrial, unfamiliar and resilient also consider it more compatible with wind turbines. The perception of the landscape’s compatibility with wind turbines proved to be a dominant factor shaping attitudes towards the project. The acceptance of wind turbines is not, however, inconsistent with the perception of landscape as beautiful, wild and unique. Participants from more densely populated countries and countries with a developed wind energy industry were more tolerant of wind turbines in the Icelandic landscape.

  17. Nutritional geometry: gorillas prioritize non-protein energy while consuming surplus protein.

    Science.gov (United States)

    Rothman, Jessica M; Raubenheimer, David; Chapman, Colin A

    2011-12-23

    It is widely assumed that terrestrial food webs are built on a nitrogen-limited base and consequently herbivores must compensate through selection of high-protein foods and efficient nitrogen retention. Like many folivorous primates, gorillas' diet selection supports this assumption, as they apparently prefer protein-rich foods. Our study of mountain gorillas (Gorilla beringei) in Uganda revealed that, in some periods, carbohydrate-rich fruits displace a large portion of protein-rich leaves in their diet. We show that non-protein energy (NPE) intake was invariant throughout the year, whereas protein intake was substantially higher when leaves were the major portion of the diet. This pattern of macronutrient intake suggests that gorillas prioritize NPE and, to achieve this when leaves are the major dietary item, they over-eat protein. The concentrations of protein consumed in relation to energy when leaves were the major portion of the diet were close to the maximum recommended for humans and similar to high-protein human weight-loss diets. By contrast, the concentrations of protein in relation to energy when gorillas ate fruit-dominated diets were similar to those recommended for humans. Our results question the generality of nitrogen limitation in terrestrial herbivores and provide a fascinating contrast with human macronutrient intake.

  18. Nutritional geometry: gorillas prioritize non-protein energy while consuming surplus protein

    Science.gov (United States)

    Rothman, Jessica M.; Raubenheimer, David; Chapman, Colin A.

    2011-01-01

    It is widely assumed that terrestrial food webs are built on a nitrogen-limited base and consequently herbivores must compensate through selection of high-protein foods and efficient nitrogen retention. Like many folivorous primates, gorillas' diet selection supports this assumption, as they apparently prefer protein-rich foods. Our study of mountain gorillas (Gorilla beringei) in Uganda revealed that, in some periods, carbohydrate-rich fruits displace a large portion of protein-rich leaves in their diet. We show that non-protein energy (NPE) intake was invariant throughout the year, whereas protein intake was substantially higher when leaves were the major portion of the diet. This pattern of macronutrient intake suggests that gorillas prioritize NPE and, to achieve this when leaves are the major dietary item, they over-eat protein. The concentrations of protein consumed in relation to energy when leaves were the major portion of the diet were close to the maximum recommended for humans and similar to high-protein human weight-loss diets. By contrast, the concentrations of protein in relation to energy when gorillas ate fruit-dominated diets were similar to those recommended for humans. Our results question the generality of nitrogen limitation in terrestrial herbivores and provide a fascinating contrast with human macronutrient intake. PMID:21632622

  19. Approximate scaling properties of RNA free energy landscapes

    Science.gov (United States)

    Baskaran, S.; Stadler, P. F.; Schuster, P.

    1996-01-01

    RNA free energy landscapes are analysed by means of "time-series" that are obtained from random walks restricted to excursion sets. The power spectra, the scaling of the jump size distribution, and the scaling of the curve length measured with different yard stick lengths are used to describe the structure of these "time series". Although they are stationary by construction, we find that their local behavior is consistent with both AR(1) and self-affine processes. Random walks confined to excursion sets (i.e., with the restriction that the fitness value exceeds a certain threshold at each step) exhibit essentially the same statistics as free random walks. We find that an AR(1) time series is in general approximately self-affine on timescales up to approximately the correlation length. We present an empirical relation between the correlation parameter rho of the AR(1) model and the exponents characterizing self-affinity.

  20. Simple solvable energy-landscape model that shows a thermodynamic phase transition and a glass transition.

    Science.gov (United States)

    Naumis, Gerardo G

    2012-06-01

    When a liquid melt is cooled, a glass or phase transition can be obtained depending on the cooling rate. Yet, this behavior has not been clearly captured in energy-landscape models. Here, a model is provided in which two key ingredients are considered in the landscape, metastable states and their multiplicity. Metastable states are considered as in two level system models. However, their multiplicity and topology allows a phase transition in the thermodynamic limit for slow cooling, while a transition to the glass is obtained for fast cooling. By solving the corresponding master equation, the minimal speed of cooling required to produce the glass is obtained as a function of the distribution of metastable states.

  1. Binding free energy analysis of protein-protein docking model structures by evERdock.

    Science.gov (United States)

    Takemura, Kazuhiro; Matubayasi, Nobuyuki; Kitao, Akio

    2018-03-14

    To aid the evaluation of protein-protein complex model structures generated by protein docking prediction (decoys), we previously developed a method to calculate the binding free energies for complexes. The method combines a short (2 ns) all-atom molecular dynamics simulation with explicit solvent and solution theory in the energy representation (ER). We showed that this method successfully selected structures similar to the native complex structure (near-native decoys) as the lowest binding free energy structures. In our current work, we applied this method (evERdock) to 100 or 300 model structures of four protein-protein complexes. The crystal structures and the near-native decoys showed the lowest binding free energy of all the examined structures, indicating that evERdock can successfully evaluate decoys. Several decoys that show low interface root-mean-square distance but relatively high binding free energy were also identified. Analysis of the fraction of native contacts, hydrogen bonds, and salt bridges at the protein-protein interface indicated that these decoys were insufficiently optimized at the interface. After optimizing the interactions around the interface by including interfacial water molecules, the binding free energies of these decoys were improved. We also investigated the effect of solute entropy on binding free energy and found that consideration of the entropy term does not necessarily improve the evaluations of decoys using the normal model analysis for entropy calculation.

  2. Evidence and opportunities for integrating landscape ecology into natural resource planning across multiple-use landscapes

    Science.gov (United States)

    Trammel, E. Jamie; Carter, Sarah; Haby, Travis S.; Taylor, Jason J.

    2018-01-01

    Enhancing natural resource management has been a focus of landscape ecology since its inception, but numerous authors argue that landscape ecology has not yet been effective in achieving the underlying goal of planning and designing sustainable landscapes. We developed nine questions reflecting the application of fundamental research topics in landscape ecology to the landscape planning process and reviewed two recent landscape-scale plans in western North America for evidence of these concepts in plan decisions. Both plans considered multiple resources, uses, and values, including energy development, recreation, conservation, and protection of cultural and historic resources. We found that land use change and multiscale perspectives of resource uses and values were very often apparent in planning decisions. Pattern-process relationships, connectivity and fragmentation, ecosystem services, landscape history, and climate change were reflected less frequently. Landscape sustainability was considered only once in the 295 decisions reviewed, and outputs of landscape models were not referenced. We suggest six actionable opportunities for further integrating landscape ecology concepts into landscape planning efforts: 1) use landscape sustainability as an overarching goal, 2) adopt a broad ecosystem services framework, 3) explore the role of landscape history more comprehensively, 4) regularly consider and accommodate potential effects of climate change, 5) use landscape models to support plan decisions, and 6) promote a greater presence of landscape ecologists within agencies that manage large land bases and encourage active involvement in agency planning efforts. Together these actions may improve the defensibility, durability, and sustainability of landscape plan decisions.

  3. A cavitation transition in the energy landscape of simple cohesive liquids and glasses

    International Nuclear Information System (INIS)

    Altabet, Y. Elia; Debenedetti, Pablo G.; Stillinger, Frank H.

    2016-01-01

    In particle systems with cohesive interactions, the pressure-density relationship of the mechanically stable inherent structures sampled along a liquid isotherm (i.e., the equation of state of an energy landscape) will display a minimum at the Sastry density ρ S . The tensile limit at ρ S is due to cavitation that occurs upon energy minimization, and previous characterizations of this behavior suggested that ρ S is a spinodal-like limit that separates all homogeneous and fractured inherent structures. Here, we revisit the phenomenology of Sastry behavior and find that it is subject to considerable finite-size effects, and the development of the inherent structure equation of state with system size is consistent with the finite-size rounding of an athermal phase transition. What appears to be a continuous spinodal-like point at finite system sizes becomes discontinuous in the thermodynamic limit, indicating behavior akin to a phase transition. We also study cavitation in glassy packings subjected to athermal expansion. Many individual expansion trajectories averaged together produce a smooth equation of state, which we find also exhibits features of finite-size rounding, and the examples studied in this work give rise to a larger limiting tension than for the corresponding landscape equation of state.

  4. Smart Landscape. The architecture of the "micro smart grid" as a resilience strategy for landscape

    OpenAIRE

    Garbarini, Giulia

    2018-01-01

    “Smart Landscape”, starting from energy devices for the management and distribution of electricity resources, tends to define a possible vision of landscape. The main structure and process are based on the architecture of a “micro smart grid”, which is generally associated with urban energy grids and districts, but may become a figurative reference for new forms of landscape, such as “Smart Landscape”. The output of the research would be to show how the main strategies of “Smart Landsc...

  5. Communication: Theoretical prediction of free-energy landscapes for complex self-assembly

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, William M.; Reinhardt, Aleks; Frenkel, Daan [Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW (United Kingdom)

    2015-01-14

    We present a technique for calculating free-energy profiles for the nucleation of multicomponent structures that contain as many species as building blocks. We find that a key factor is the topology of the graph describing the connectivity of the target assembly. By considering the designed interactions separately from weaker, incidental interactions, our approach yields predictions for the equilibrium yield and nucleation barriers. These predictions are in good agreement with corresponding Monte Carlo simulations. We show that a few fundamental properties of the connectivity graph determine the most prominent features of the assembly thermodynamics. Surprisingly, we find that polydispersity in the strengths of the designed interactions stabilizes intermediate structures and can be used to sculpt the free-energy landscape for self-assembly. Finally, we demonstrate that weak incidental interactions can preclude assembly at equilibrium due to the combinatorial possibilities for incorrect association.

  6. The environmental benefits of cellulosic energy crops at a landscape scale

    International Nuclear Information System (INIS)

    Graham, R.L.; Liu, W.; English, B.C.

    1995-01-01

    The objective of this paper is to present a broad overview of the potential environmental impacts of biomass energy from energy crops--particularly the cellulosic energy crops current under development. For this discussion, the term energy crop refers to a crop grown primarily to create feedstock for either making biofuels such as ethanol or burning in a heat or electricity generation facility. Cellulosic energy crops are designed to be used in cellulose-based ethanol conversion processes (as opposed to starch or sugar-based ethanol conversion processes). As more cellulose can be produced per hectare of land than can sugar or starch, the cellulose-based ethanol conversion process is a more efficient sue of land for ethanol production. Assessing the environmental impacts of biomass energy from energy crops is complex because the environmental impact of using biomass for energy must be considered in the context of alternative energy options while the environmental impact of producing biomass from energy crops must be considered in the context of alternative land-uses. Using biomass-derived energy can reduce greenhouse gas emissions or increase them; growing biomass energy crops can enhance soil fertility or degrade it. Without knowing the context of the biomass energy, one can say little about its specific environmental impacts. The primary focus of this paper is an evaluation of the environmental impacts of growing cellulosic energy crops especially at the landscape or regional scale. However, to set the stage for this discussion, the authors begin by comparing the environmental advantages and disadvantages of biomass-derived energy relative to other energy alternatives such as coal, hydropower, nuclear power, oil/gasoline, natural gas and photovoltaics

  7. Morphing methods to visualize coarse-grained protein dynamics.

    Science.gov (United States)

    Weiss, Dahlia R; Koehl, Patrice

    2014-01-01

    Morphing was initially developed as a cinematic effect, where one image is seamlessly transformed into another image. The technique was widely adopted by biologists to visualize the transition between protein conformational states, generating an interpolated pathway from an initial to a final protein structure. Geometric morphing seeks to create visually suggestive movies that illustrate structural changes between conformations but do not necessarily represent a biologically relevant pathway, while minimum energy path (MEP) interpolations aim at describing the true transition state between the crystal structure minima in the energy landscape.

  8. Investigation of the Structures and Energy Landscapes of Thiocyanate-Water Clusters

    Directory of Open Access Journals (Sweden)

    Lewis C. Smeeton

    2017-03-01

    Full Text Available The Basin Hopping search method is used to find the global minima (GM and map the energy landscapes of thiocyanate-water clusters, (SCN−(H2On with 3–50 water molecules, with empirical potentials describing the ion-water and water-water interactions. (It should be noted that beyond n = 23, the lowest energy structures were only found in 1 out of 8 searches so they are unlikely to be the true GM but are indicative low energy structures. As for pure water clusters, the low energy isomers of thiocyanate-water clusters show a preponderance of fused water cubes and pentagonal prisms, with the weakly solvated thiocyanate ion lying on the surface, replacing two water molecules along an edge of a water polyhedron and with the sulfur atom in lower coordinated sites than nitrogen. However, by comparison with Density Functional Theory (DFT calculations, the empirical potential is found to overestimate the strength of the thiocyanate-water interaction, especially O–H⋯S, with low energy DFT structures having lower coordinate N and (especially S atoms than for the empirical potential. In the case of these finite ion-water clusters, the chaotropic (“disorder-making” thiocyanate ion weakens the water cluster structure but the water molecule arrangement is not significantly changed.

  9. Visualization of protein folding funnels in lattice models.

    Directory of Open Access Journals (Sweden)

    Antonio B Oliveira

    Full Text Available Protein folding occurs in a very high dimensional phase space with an exponentially large number of states, and according to the energy landscape theory it exhibits a topology resembling a funnel. In this statistical approach, the folding mechanism is unveiled by describing the local minima in an effective one-dimensional representation. Other approaches based on potential energy landscapes address the hierarchical structure of local energy minima through disconnectivity graphs. In this paper, we introduce a metric to describe the distance between any two conformations, which also allows us to go beyond the one-dimensional representation and visualize the folding funnel in 2D and 3D. In this way it is possible to assess the folding process in detail, e.g., by identifying the connectivity between conformations and establishing the paths to reach the native state, in addition to regions where trapping may occur. Unlike the disconnectivity maps method, which is based on the kinetic connections between states, our methodology is based on structural similarities inferred from the new metric. The method was developed in a 27-mer protein lattice model, folded into a 3×3×3 cube. Five sequences were studied and distinct funnels were generated in an analysis restricted to conformations from the transition-state to the native configuration. Consistent with the expected results from the energy landscape theory, folding routes can be visualized to probe different regions of the phase space, as well as determine the difficulty in folding of the distinct sequences. Changes in the landscape due to mutations were visualized, with the comparison between wild and mutated local minima in a single map, which serves to identify different trapping regions. The extension of this approach to more realistic models and its use in combination with other approaches are discussed.

  10. Time Series Analysis of Energy Production and Associated Landscape Fragmentation in the Eagle Ford Shale Play

    Science.gov (United States)

    Pierre, Jon Paul; Young, Michael H.; Wolaver, Brad D.; Andrews, John R.; Breton, Caroline L.

    2017-11-01

    Spatio-temporal trends in infrastructure footprints, energy production, and landscape alteration were assessed for the Eagle Ford Shale of Texas. The period of analysis was over four 2-year periods (2006-2014). Analyses used high-resolution imagery, as well as pipeline data to map EF infrastructure. Landscape conditions from 2006 were used as baseline. Results indicate that infrastructure footprints varied from 94.5 km2 in 2008 to 225.0 km2 in 2014. By 2014, decreased land-use intensities (ratio of land alteration to energy production) were noted play-wide. Core-area alteration by period was highest (3331.6 km2) in 2008 at the onset of play development, and increased from 582.3 to 3913.9 km2 by 2014, though substantial revegetation of localized core areas was observed throughout the study (i.e., alteration improved in some areas and worsened in others). Land-use intensity in the eastern portion of the play was consistently lower than that in the western portion, while core alteration remained relatively constant east to west. Land alteration from pipeline construction was 65 km2 for all time periods, except in 2010 when alteration was recorded at 47 km2. Percent of total alteration from well-pad construction increased from 27.3% in 2008 to 71.5% in 2014. The average number of wells per pad across all 27 counties increased from 1.15 to 1.7. This study presents a framework for mapping landscape alteration from oil and gas infrastructure development. However, the framework could be applied to other energy development programs, such as wind or solar fields, or any other regional infrastructure development program.

  11. Nonequilibrium landscape theory of neural networks.

    Science.gov (United States)

    Yan, Han; Zhao, Lei; Hu, Liang; Wang, Xidi; Wang, Erkang; Wang, Jin

    2013-11-05

    The brain map project aims to map out the neuron connections of the human brain. Even with all of the wirings mapped out, the global and physical understandings of the function and behavior are still challenging. Hopfield quantified the learning and memory process of symmetrically connected neural networks globally through equilibrium energy. The energy basins of attractions represent memories, and the memory retrieval dynamics is determined by the energy gradient. However, the realistic neural networks are asymmetrically connected, and oscillations cannot emerge from symmetric neural networks. Here, we developed a nonequilibrium landscape-flux theory for realistic asymmetrically connected neural networks. We uncovered the underlying potential landscape and the associated Lyapunov function for quantifying the global stability and function. We found the dynamics and oscillations in human brains responsible for cognitive processes and physiological rhythm regulations are determined not only by the landscape gradient but also by the flux. We found that the flux is closely related to the degrees of the asymmetric connections in neural networks and is the origin of the neural oscillations. The neural oscillation landscape shows a closed-ring attractor topology. The landscape gradient attracts the network down to the ring. The flux is responsible for coherent oscillations on the ring. We suggest the flux may provide the driving force for associations among memories. We applied our theory to rapid-eye movement sleep cycle. We identified the key regulation factors for function through global sensitivity analysis of landscape topography against wirings, which are in good agreements with experiments.

  12. Structure prediction of nanoclusters; a direct or a pre-screened search on the DFT energy landscape?

    Science.gov (United States)

    Farrow, M R; Chow, Y; Woodley, S M

    2014-10-21

    The atomic structure of inorganic nanoclusters obtained via a search for low lying minima on energy landscapes, or hypersurfaces, is reported for inorganic binary compounds: zinc oxide (ZnO)n, magnesium oxide (MgO)n, cadmium selenide (CdSe)n, and potassium fluoride (KF)n, where n = 1-12 formula units. The computational cost of each search is dominated by the effort to evaluate each sample point on the energy landscape and the number of required sample points. The effect of changing the balance between these two factors on the success of the search is investigated. The choice of sample points will also affect the number of required data points and therefore the efficiency of the search. Monte Carlo based global optimisation routines (evolutionary and stochastic quenching algorithms) within a new software package, viz. Knowledge Led Master Code (KLMC), are employed to search both directly and after pre-screening on the DFT energy landscape. Pre-screening includes structural relaxation to minimise a cheaper energy function - based on interatomic potentials - and is found to improve significantly the search efficiency, and typically reduces the number of DFT calculations required to locate the local minima by more than an order of magnitude. Although the choice of functional form is important, the approach is robust to small changes to the interatomic potential parameters. The computational cost of initial DFT calculations of each structure is reduced by employing Gaussian smearing to the electronic energy levels. Larger (KF)n nanoclusters are predicted to form cuboid cuts from the rock-salt phase, but also share many structural motifs with (MgO)n for smaller clusters. The transition from 2D rings to 3D (bubble, or fullerene-like) structures occur at a larger cluster size for (ZnO)n and (CdSe)n. Differences between the HOMO and LUMO energies, for all the compounds apart from KF, are in the visible region of the optical spectrum (2-3 eV); KF lies deep in the UV region

  13. Design of Protein Multi-specificity Using an Independent Sequence Search Reduces the Barrier to Low Energy Sequences.

    Directory of Open Access Journals (Sweden)

    Alexander M Sevy

    2015-07-01

    Full Text Available Computational protein design has found great success in engineering proteins for thermodynamic stability, binding specificity, or enzymatic activity in a 'single state' design (SSD paradigm. Multi-specificity design (MSD, on the other hand, involves considering the stability of multiple protein states simultaneously. We have developed a novel MSD algorithm, which we refer to as REstrained CONvergence in multi-specificity design (RECON. The algorithm allows each state to adopt its own sequence throughout the design process rather than enforcing a single sequence on all states. Convergence to a single sequence is encouraged through an incrementally increasing convergence restraint for corresponding positions. Compared to MSD algorithms that enforce (constrain an identical sequence on all states the energy landscape is simplified, which accelerates the search drastically. As a result, RECON can readily be used in simulations with a flexible protein backbone. We have benchmarked RECON on two design tasks. First, we designed antibodies derived from a common germline gene against their diverse targets to assess recovery of the germline, polyspecific sequence. Second, we design "promiscuous", polyspecific proteins against all binding partners and measure recovery of the native sequence. We show that RECON is able to efficiently recover native-like, biologically relevant sequences in this diverse set of protein complexes.

  14. Anomalous dimensionality dependence of diffusion in a rugged energy landscape: How pathological is one dimension?

    Science.gov (United States)

    Seki, Kazuhiko; Bagchi, Kaushik; Bagchi, Biman

    2016-05-01

    Diffusion in one dimensional rugged energy landscape (REL) is predicted to be pathologically different (from any higher dimension) with a much larger chance of encountering broken ergodicity [D. L. Stein and C. M. Newman, AIP Conf. Proc. 1479, 620 (2012)]. However, no quantitative study of this difference has been reported, despite the prevalence of multidimensional physical models in the literature (like a high dimensional funnel guiding protein folding/unfolding). Paradoxically, some theoretical studies of these phenomena still employ a one dimensional diffusion description for analytical tractability. We explore the dimensionality dependent diffusion on REL by carrying out an effective medium approximation based analytical calculations and compare them with the available computer simulation results. We find that at an intermediate level of ruggedness (assumed to have a Gaussian distribution), where diffusion is well-defined, the value of the effective diffusion coefficient depends on dimensionality and changes (increases) by several factors (˜5-10) in going from 1d to 2d. In contrast, the changes in subsequent transitions (like 2d to 3d and 3d to 4d and so on) are far more modest, of the order of 10-20% only. When ruggedness is given by random traps with an exponential distribution of barrier heights, the mean square displacement (MSD) is sub-diffusive (a well-known result), but the growth of MSD is described by different exponents in one and higher dimensions. The reason for such strong ruggedness induced retardation in the case of one dimensional REL is discussed. We also discuss the special limiting case of infinite dimension (d = ∞) where the effective medium approximation becomes exact and where theoretical results become simple. We discuss, for the first time, the role of spatial correlation in the landscape on diffusion of a random walker.

  15. Supplementing an energy adequate, higher protein diet with protein does not enhance fat-free mass restoration after short-term severe negative energy balance.

    Science.gov (United States)

    Berryman, C E; Sepowitz, J J; McClung, H L; Lieberman, H R; Farina, E K; McClung, J P; Ferrando, A A; Pasiakos, S M

    2017-06-01

    Negative energy balance during military operations can be severe and result in significant reductions in fat-free mass (FFM). Consuming supplemental high-quality protein following such military operations may accelerate restoration of FFM. Body composition (dual-energy X-ray absorptiometry) and whole body protein turnover (single-pool [ 15 N]alanine method) were determined before (PRE) and after 7 days (POST) of severe negative energy balance during military training in 63 male US Marines (means ± SD, 25 ± 3 yr, 84 ± 9 kg). After POST measures were collected, volunteers were randomized to receive higher protein (HIGH: 1,103 kcal/day, 133 g protein/day), moderate protein (MOD: 974 kcal/day, 84 g protein/day), or carbohydrate-based low protein control (CON: 1,042 kcal/day, 7 g protein/day) supplements, in addition to a self-selected, ad libitum diet, for the 27-day intervention (REFED). Measurements were repeated POST-REFED. POST total body mass (TBM; -5.8 ± 1.0 kg, -7.0%), FFM (-3.1 ± 1.6 kg, -4.7%), and net protein balance (-1.7 ± 1.1 g protein·kg -1 ·day -1 ) were lower and proteolysis (1.1 ± 1.9 g protein·kg -1 ·day -1 ) was higher compared with PRE ( P energy (4,498 ± 725 kcal/day). All volunteers, independent of group assignment, achieved positive net protein balance (0.4 ± 1.0 g protein·kg -1 ·day -1 ) and gained TBM (5.9 ± 1.7 kg, 7.8%) and FFM (3.6 ± 1.8 kg, 5.7%) POST-REFED compared with POST ( P energy-adequate, higher protein diets with additional protein may not be necessary to restore FFM after short-term severe negative energy balance. NEW & NOTEWORTHY This article demonstrates 1 ) the majority of physiological decrements incurred during military training (e.g., total and fat-free mass loss), with the exception of net protein balance, resolve and return to pretraining values after 27 days and 2 ) protein supplementation, in addition to an ad libitum, higher protein (~2.0 g·kg -1 ·day -1 ), energy adequate diet, is not necessary to

  16. The inherent dynamics of a molecular liquid: Geodesic pathways through the potential energy landscape of a liquid of linear molecules

    Science.gov (United States)

    Jacobson, Daniel; Stratt, Richard M.

    2014-05-01

    Because the geodesic pathways that a liquid follows through its potential energy landscape govern its slow, diffusive motion, we suggest that these pathways are logical candidates for the title of a liquid's "inherent dynamics." Like their namesake "inherent structures," these objects are simply features of the system's potential energy surface and thus provide views of the system's structural evolution unobstructed by thermal kinetic energy. This paper shows how these geodesic pathways can be computed for a liquid of linear molecules, allowing us to see precisely how such molecular liquids mix rotational and translational degrees of freedom into their dynamics. The ratio of translational to rotational components of the geodesic path lengths, for example, is significantly larger than would be expected on equipartition grounds, with a value that scales with the molecular aspect ratio. These and other features of the geodesics are consistent with a picture in which molecular reorientation adiabatically follows translation—molecules largely thread their way through narrow channels available in the potential energy landscape.

  17. Obsolete or resurgent? The International Energy Agency in a changing global landscape

    International Nuclear Information System (INIS)

    Van de Graaf, Thijs

    2012-01-01

    Founded in response to the 1973 oil shock, the International Energy Agency (IEA) is arguably still the most important multilateral organization for energy-importing countries. Yet, the global geopolitical landscape has changed considerably since the IEA's creation. The rise of new energy consumers, new energy-related challenges and new international energy forums prompt a rethink of the agency's current role and institutional design. This article seeks to contribute to the recent debate on the future role of the IEA by examining specific drivers, avenues and constraints for institutional reform. The method used is SWOT analysis, which allows to summarize the key factors emanating from an assessment of an organization's internal characteristics (strengths and weaknesses) and its external environment (opportunities and threats). Building on this SWOT analysis, the article formulates a strategy for the IEA to remain the focal point in global energy governance. Key elements of this strategy include: stronger engagement with new consumers, rapprochement with OPEC, becoming a leading voice in the energy transition, and changing the agency's internal governance practices. - Highlights: ► The IEA is challenged by the rise of new consumers, threats and organizations. ► Assessment of the agency’s internal characteristics and external environment. ► The IEA needs to step up its outreach policy and fully embrace sustainable energy.

  18. Efficient Determination of Free Energy Landscapes in Multiple Dimensions from Biased Umbrella Sampling Simulations Using Linear Regression.

    Science.gov (United States)

    Meng, Yilin; Roux, Benoît

    2015-08-11

    The weighted histogram analysis method (WHAM) is a standard protocol for postprocessing the information from biased umbrella sampling simulations to construct the potential of mean force with respect to a set of order parameters. By virtue of the WHAM equations, the unbiased density of state is determined by satisfying a self-consistent condition through an iterative procedure. While the method works very effectively when the number of order parameters is small, its computational cost grows rapidly in higher dimension. Here, we present a simple and efficient alternative strategy, which avoids solving the self-consistent WHAM equations iteratively. An efficient multivariate linear regression framework is utilized to link the biased probability densities of individual umbrella windows and yield an unbiased global free energy landscape in the space of order parameters. It is demonstrated with practical examples that free energy landscapes that are comparable in accuracy to WHAM can be generated at a small fraction of the cost.

  19. Two states or not two states: Single-molecule folding studies of protein L

    Science.gov (United States)

    Aviram, Haim Yuval; Pirchi, Menahem; Barak, Yoav; Riven, Inbal; Haran, Gilad

    2018-03-01

    Experimental tools of increasing sophistication have been employed in recent years to study protein folding and misfolding. Folding is considered a complex process, and one way to address it is by studying small proteins, which seemingly possess a simple energy landscape with essentially only two stable states, either folded or unfolded. The B1-IgG binding domain of protein L (PL) is considered a model two-state folder, based on measurements using a wide range of experimental techniques. We applied single-molecule fluorescence resonance energy transfer (FRET) spectroscopy in conjunction with a hidden Markov model analysis to fully characterize the energy landscape of PL and to extract the kinetic properties of individual molecules of the protein. Surprisingly, our studies revealed the existence of a third state, hidden under the two-state behavior of PL due to its small population, ˜7%. We propose that this minority intermediate involves partial unfolding of the two C-terminal β strands of PL. Our work demonstrates that single-molecule FRET spectroscopy can be a powerful tool for a comprehensive description of the folding dynamics of proteins, capable of detecting and characterizing relatively rare metastable states that are difficult to observe in ensemble studies.

  20. A high protein diet upregulated whole-body protein turnover during energy deficit

    Science.gov (United States)

    The effects of higher protein diets and sustained energy deficit (ED) on whole-body protein turnover (WBPTO) are not well described. This study examined whether dietary protein level influences whole-body protein breakdown (Ra), non-oxidative leucine disposal (NOLD), and oxidation (Ox) during ED. ...

  1. Tuning Surface Energy Landscapes in Metallic Quantum Films using Alkali Adsorbates

    Science.gov (United States)

    Khajetoorians, Alexander; Qin, Shengyong; Zhu, Wenguang; Eisele, Holger; Zhang, Zhenyu; Shih, Chih-Kang

    2008-03-01

    Quantum confinement shows a strong interplay with growth and kinetics in thin metal systems where the Fermi wavelength has a special relationship to the surface normal lattice constant. In the case of Pb/Si(111) systems, this relationship reveals an interesting thickness-dependent bilayer oscillation in the density of states and surface energy up to a phase. In this paper, we report on a novel effect: tuning of the energy landscape of a flat-top quantum Pb mesa using Cs adsorbates. Using STM/STS, we show that depositing Cs adsorbates on a thin Pb mesa promotes quantum stable Pb nanoislands on preferentially unstable thicknesses. Thickness-dependent nanoisland densities show a strong bilayer oscillation correlating with quantum stability. By modifying the Cs coverage on the mesa surface, we can tune the lateral size distribution of the nanoislands and the overall amplitude of the island density oscillation. Nanoisland formation is linked to a step decoration of Cs adatoms along the step edge of the nanoisland.

  2. Protein Frustratometer 2: a tool to localize energetic frustration in protein molecules, now with electrostatics.

    Science.gov (United States)

    Parra, R Gonzalo; Schafer, Nicholas P; Radusky, Leandro G; Tsai, Min-Yeh; Guzovsky, A Brenda; Wolynes, Peter G; Ferreiro, Diego U

    2016-07-08

    The protein frustratometer is an energy landscape theory-inspired algorithm that aims at localizing and quantifying the energetic frustration present in protein molecules. Frustration is a useful concept for analyzing proteins' biological behavior. It compares the energy distributions of the native state with respect to structural decoys. The network of minimally frustrated interactions encompasses the folding core of the molecule. Sites of high local frustration often correlate with functional regions such as binding sites and regions involved in allosteric transitions. We present here an upgraded version of a webserver that measures local frustration. The new implementation that allows the inclusion of electrostatic energy terms, important to the interactions with nucleic acids, is significantly faster than the previous version enabling the analysis of large macromolecular complexes within a user-friendly interface. The webserver is freely available at URL: http://frustratometer.qb.fcen.uba.ar. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Free energy landscape and cooperatively rearranging region in a hard sphere glass

    Science.gov (United States)

    Yoshidome, Takashi; Yoshimori, Akira; Odagaki, Takashi

    2007-08-01

    Exploiting the density functional theory, we calculate the free energy landscape (FEL) of the hard sphere glass in three dimensions. From the FEL, we estimate the number of the particles in the cooperatively rearranging region (CRR). We find that the density dependence of the number of the particles in the CRR is expressed as a power law function of the density. Analyzing the relaxation process in the CRR, we also find that the string motion is the elementary process for the structural relaxation, which leads to the natural definition of the simultaneously rearranging region as the particles displaced in the string motion.

  4. The dynamics of single protein molecules is non-equilibrium and self-similar over thirteen decades in time

    Science.gov (United States)

    Hu, Xiaohu; Hong, Liang; Dean Smith, Micholas; Neusius, Thomas; Cheng, Xiaolin; Smith, Jeremy C.

    2016-02-01

    Internal motions of proteins are essential to their function. The time dependence of protein structural fluctuations is highly complex, manifesting subdiffusive, non-exponential behaviour with effective relaxation times existing over many decades in time, from ps up to ~102 s (refs ,,,). Here, using molecular dynamics simulations, we show that, on timescales from 10-12 to 10-5 s, motions in single proteins are self-similar, non-equilibrium and exhibit ageing. The characteristic relaxation time for a distance fluctuation, such as inter-domain motion, is observation-time-dependent, increasing in a simple, power-law fashion, arising from the fractal nature of the topology and geometry of the energy landscape explored. Diffusion over the energy landscape follows a non-ergodic continuous time random walk. Comparison with single-molecule experiments suggests that the non-equilibrium self-similar dynamical behaviour persists up to timescales approaching the in vivo lifespan of individual protein molecules.

  5. Energy requirements, protein-energy metabolism and balance, and carbohydrates in preterm infants.

    Science.gov (United States)

    Hay, William W; Brown, Laura D; Denne, Scott C

    2014-01-01

    Energy is necessary for all vital functions of the body at molecular, cellular, organ, and systemic levels. Preterm infants have minimum energy requirements for basal metabolism and growth, but also have requirements for unique physiology and metabolism that influence energy expenditure. These include body size, postnatal age, physical activity, dietary intake, environmental temperatures, energy losses in the stool and urine, and clinical conditions and diseases, as well as changes in body composition. Both energy and protein are necessary to produce normal rates of growth. Carbohydrates (primarily glucose) are principle sources of energy for the brain and heart until lipid oxidation develops over several days to weeks after birth. A higher protein/energy ratio is necessary in most preterm infants to approximate normal intrauterine growth rates. Lean tissue is predominantly produced during early gestation, which continues through to term. During later gestation, fat accretion in adipose tissue adds increasingly large caloric requirements to the lean tissue growth. Once protein intake is sufficient to promote net lean body accretion, additional energy primarily produces more body fat, which increases almost linearly at energy intakes >80-90 kcal/kg/day in normal, healthy preterm infants. Rapid gains in adiposity have the potential to produce later life obesity, an increasingly recognized risk of excessive energy intake. In addition to fundamental requirements for glucose, protein, and fat, a variety of non-glucose carbohydrates found in human milk may have important roles in promoting growth and development, as well as production of a gut microbiome that could protect against necrotizing enterocolitis. © 2014 S. Karger AG, Basel.

  6. Computational design of RNAs with complex energy landscapes.

    Science.gov (United States)

    Höner zu Siederdissen, Christian; Hammer, Stefan; Abfalter, Ingrid; Hofacker, Ivo L; Flamm, Christoph; Stadler, Peter F

    2013-12-01

    RNA has become an integral building material in synthetic biology. Dominated by their secondary structures, which can be computed efficiently, RNA molecules are amenable not only to in vitro and in vivo selection, but also to rational, computation-based design. While the inverse folding problem of constructing an RNA sequence with a prescribed ground-state structure has received considerable attention for nearly two decades, there have been few efforts to design RNAs that can switch between distinct prescribed conformations. We introduce a user-friendly tool for designing RNA sequences that fold into multiple target structures. The underlying algorithm makes use of a combination of graph coloring and heuristic local optimization to find sequences whose energy landscapes are dominated by the prescribed conformations. A flexible interface allows the specification of a wide range of design goals. We demonstrate that bi- and tri-stable "switches" can be designed easily with moderate computational effort for the vast majority of compatible combinations of desired target structures. RNAdesign is freely available under the GPL-v3 license. Copyright © 2013 Wiley Periodicals, Inc.

  7. Physical mechanism of mind changes and tradeoffs among speed, accuracy, and energy cost in brain decision making: Landscape, flux, and path perspectives

    International Nuclear Information System (INIS)

    Yan Han; Wang Jin; Zhang Kun

    2016-01-01

    Cognitive behaviors are determined by underlying neural networks. Many brain functions, such as learning and memory, have been successfully described by attractor dynamics. For decision making in the brain, a quantitative description of global attractor landscapes has not yet been completely given. Here, we developed a theoretical framework to quantify the landscape associated with the steady state probability distributions and associated steady state curl flux, measuring the degree of non-equilibrium through the degree of detailed balance breaking for decision making. We quantified the decision-making processes with optimal paths from the undecided attractor states to the decided attractor states, which are identified as basins of attractions, on the landscape. Both landscape and flux determine the kinetic paths and speed. The kinetics and global stability of decision making are explored by quantifying the landscape topography through the barrier heights and the mean first passage time. Our theoretical predictions are in agreement with experimental observations: more errors occur under time pressure. We quantitatively explored two mechanisms of the speed-accuracy tradeoff with speed emphasis and further uncovered the tradeoffs among speed, accuracy, and energy cost. Our results imply that there is an optimal balance among speed, accuracy, and the energy cost in decision making. We uncovered the possible mechanisms of changes of mind and how mind changes improve performance in decision processes. Our landscape approach can help facilitate an understanding of the underlying physical mechanisms of cognitive processes and identify the key factors in the corresponding neural networks. (paper)

  8. Shedding Light on Protein Folding, Structural and Functional Dynamics by Single Molecule Studies

    Directory of Open Access Journals (Sweden)

    Krutika Bavishi

    2014-11-01

    Full Text Available The advent of advanced single molecule measurements unveiled a great wealth of dynamic information revolutionizing our understanding of protein dynamics and behavior in ways unattainable by conventional bulk assays. Equipped with the ability to record distribution of behaviors rather than the mean property of a population, single molecule measurements offer observation and quantification of the abundance, lifetime and function of multiple protein states. They also permit the direct observation of the transient and rarely populated intermediates in the energy landscape that are typically averaged out in non-synchronized ensemble measurements. Single molecule studies have thus provided novel insights about how the dynamic sampling of the free energy landscape dictates all aspects of protein behavior; from its folding to function. Here we will survey some of the state of the art contributions in deciphering mechanisms that underlie protein folding, structural and functional dynamics by single molecule fluorescence microscopy techniques. We will discuss a few selected examples highlighting the power of the emerging techniques and finally discuss the future improvements and directions.

  9. the effect of dietary energy and protein levels on the composition

    African Journals Online (AJOL)

    Zannel

    Keywords: Breeding ostriches, nutrition, energy, protein, amino acids, egg ... Yolk is an important nutritional component of the avian egg because .... 3 (energy) x 3 (protein) factorial design with energy and protein levels featuring as main factors. ... No significant interactions were observed between energy and protein levels.

  10. Exploring the energy landscape of the charge transport levels in organic semiconductors at the molecular scale.

    Science.gov (United States)

    Cornil, J; Verlaak, S; Martinelli, N; Mityashin, A; Olivier, Y; Van Regemorter, T; D'Avino, G; Muccioli, L; Zannoni, C; Castet, F; Beljonne, D; Heremans, P

    2013-02-19

    strongly interacting electron-hole pairs can potentially escape from their Coulomb well, a process that is at the heart of photoconversion or molecular doping. Yet they do, with near-quantitative yield in some cases. Limited screening by the low dielectric medium in organic materials leads to subtle static and dynamic electronic polarization effects that strongly impact the energy landscape for charges, which offers a rationale for this apparent inconsistency. In this Account, we use different theoretical approaches to predict the energy landscape of charge carriers at the molecular level and review a few case studies highlighting the role of electrostatic interactions in conjugated organic molecules. We describe the pros and cons of different theoretical approaches that provide access to the energy landscape defining the motion of charge carriers. We illustrate the applications of these approaches through selected examples involving OFETs, OLEDs, and solar cells. The three selected examples collectively show that energetic disorder governs device performances and highlights the relevance of theoretical tools to probe energy landscapes in molecular assemblies.

  11. Computed tomography in severe protein energy malnutrition.

    OpenAIRE

    Househam, K C; de Villiers, J F

    1987-01-01

    Computed tomography of the brain was performed on eight children aged 1 to 4 years with severe protein energy malnutrition. Clinical features typical of kwashiorkor were present in all the children studied. Severe cerebral atrophy or brain shrinkage according to standard radiological criteria was present in every case. The findings of this study suggest considerable cerebral insult associated with severe protein energy malnutrition.

  12. AN EVALUATION OF THE SPATIAL DIMENSION OF LANDSCAPE ...

    African Journals Online (AJOL)

    Osondu

    2012-03-30

    Mar 30, 2012 ... with adequate landscaping, - using landscape elements, to create a ... air, water and energy cycles that replenish and rejuvenate ... First, using the street map of. Ogbomoso ... swimming pools, etc, were regarded as conscious.

  13. Energy and environmental implications of novel protein production systems

    Energy Technology Data Exchange (ETDEWEB)

    Edwardson, W; Lewis, C W; Slesser, M

    1981-04-01

    The energy requirements of many novel protein production systems are compared with an examination of the relevant environmental implications of these systems. The prospects for single cell protein, leaf protein, fish farming, fish protein concentrate, algal cultivation, and hydroponic plant growth systems are investigated. Single cell protein from carbohydrate substrates, algal protein, and fish protein seem to hold much promise, as they are technologically feasible for near-term implementation and do not require major energy inputs. (2 diagrams, 1 graph, 47 references, 6 tables)

  14. Monitoring Conformational Landscape of Ovine Prion Protein Monomer Using Ion Mobility Coupled to Mass Spectrometry

    Science.gov (United States)

    Van der Rest, Guillaume; Rezaei, Human; Halgand, Frédéric

    2017-02-01

    Prion protein is involved in deadly neurodegenerative diseases. Its pathogenicity is linked to its structural conversion (α-helix to β-strand transition). However, recent studies suggest that prion protein can follow a plurality of conversion pathways, which hints towards different conformers that might coexist in solution. To gain insights on the plasticity of the ovine prion protein (PrP) monomer, wild type (A136, R154, Q171), mutants and deletions of ARQ were studied by traveling wave ion mobility experiments coupled to mass spectrometry. In order to perform the analysis of a large body of data sets, we designed and evaluated the performance of a processing pipeline based on Driftscope peak detection and a homemade script for automated peak assignment, annotation, and quantification on specific multiply charged protein data. Using this approach, we showed that in the gas phase, PrPs are represented by at least three conformer families differing in both charge state distribution and collisional cross-section, in agreement with the work of Hilton et al. (2010). We also showed that this plasticity is borne both by the N- and C-terminal domains. Effect of protein concentration, pH and temperature were also assessed, showing that (1) pH does not affect conformer distributions, (2) protein concentration modifies the conformational landscape of one mutant (I208M) only, and (3) heating leads to other unfolded species and to a modification of the conformer intensity ratios.

  15. Nonequilibrium landscape theory of neural networks

    Science.gov (United States)

    Yan, Han; Zhao, Lei; Hu, Liang; Wang, Xidi; Wang, Erkang; Wang, Jin

    2013-01-01

    The brain map project aims to map out the neuron connections of the human brain. Even with all of the wirings mapped out, the global and physical understandings of the function and behavior are still challenging. Hopfield quantified the learning and memory process of symmetrically connected neural networks globally through equilibrium energy. The energy basins of attractions represent memories, and the memory retrieval dynamics is determined by the energy gradient. However, the realistic neural networks are asymmetrically connected, and oscillations cannot emerge from symmetric neural networks. Here, we developed a nonequilibrium landscape–flux theory for realistic asymmetrically connected neural networks. We uncovered the underlying potential landscape and the associated Lyapunov function for quantifying the global stability and function. We found the dynamics and oscillations in human brains responsible for cognitive processes and physiological rhythm regulations are determined not only by the landscape gradient but also by the flux. We found that the flux is closely related to the degrees of the asymmetric connections in neural networks and is the origin of the neural oscillations. The neural oscillation landscape shows a closed-ring attractor topology. The landscape gradient attracts the network down to the ring. The flux is responsible for coherent oscillations on the ring. We suggest the flux may provide the driving force for associations among memories. We applied our theory to rapid-eye movement sleep cycle. We identified the key regulation factors for function through global sensitivity analysis of landscape topography against wirings, which are in good agreements with experiments. PMID:24145451

  16. Thermal Infrared Remote Sensing for Analysis of Landscape Ecological Processes: Methods and Applications

    Science.gov (United States)

    Quattrochi, Dale A.; Luvall, Jeffrey C.

    1998-01-01

    Thermal Infrared (TIR) remote sensing data can provide important measurements of surface energy fluxes and temperatures, which are integral to understanding landscape processes and responses. One example of this is the successful application of TIR remote sensing data to estimate evapotranspiration and soil moisture, where results from a number of studies suggest that satellite-based measurements from TIR remote sensing data can lead to more accurate regional-scale estimates of daily evapotranspiration. With further refinement in analytical techniques and models, the use of TIR data from airborne and satellite sensors could be very useful for parameterizing surface moisture conditions and developing better simulations of landscape energy exchange over a variety of conditions and space and time scales. Thus, TIR remote sensing data can significantly contribute to the observation, measurement, and analysis of energy balance characteristics (i.e., the fluxes and redistribution of thermal energy within and across the land surface) as an implicit and important aspect of landscape dynamics and landscape functioning. The application of TIR remote sensing data in landscape ecological studies has been limited, however, for several fundamental reasons that relate primarily to the perceived difficulty in use and availability of these data by the landscape ecology community, and from the fragmentation of references on TIR remote sensing throughout the scientific literature. It is our purpose here to provide evidence from work that has employed TIR remote sensing for analysis of landscape characteristics to illustrate how these data can provide important data for the improved measurement of landscape energy response and energy flux relationships. We examine the direct or indirect use of TIR remote sensing data to analyze landscape biophysical characteristics, thereby offering some insight on how these data can be used more robustly to further the understanding and modeling of

  17. Examining a Thermodynamic Order Parameter of Protein Folding.

    Science.gov (United States)

    Chong, Song-Ho; Ham, Sihyun

    2018-05-08

    Dimensionality reduction with a suitable choice of order parameters or reaction coordinates is commonly used for analyzing high-dimensional time-series data generated by atomistic biomolecular simulations. So far, geometric order parameters, such as the root mean square deviation, fraction of native amino acid contacts, and collective coordinates that best characterize rare or large conformational transitions, have been prevailing in protein folding studies. Here, we show that the solvent-averaged effective energy, which is a thermodynamic quantity but unambiguously defined for individual protein conformations, serves as a good order parameter of protein folding. This is illustrated through the application to the folding-unfolding simulation trajectory of villin headpiece subdomain. We rationalize the suitability of the effective energy as an order parameter by the funneledness of the underlying protein free energy landscape. We also demonstrate that an improved conformational space discretization is achieved by incorporating the effective energy. The most distinctive feature of this thermodynamic order parameter is that it works in pointing to near-native folded structures even when the knowledge of the native structure is lacking, and the use of the effective energy will also find applications in combination with methods of protein structure prediction.

  18. Shapes of tree representations of spin-glass landscapes

    International Nuclear Information System (INIS)

    Hordijk, Wim; Fontanari, Jose F; Stadler, Peter F

    2003-01-01

    Much of the information about the multi-valley structure of disordered spin systems can be convened in a simple tree structure - a barrier tree - the leaves and internal nodes of which represent, respectively, the local minima and the lowest energy saddles connecting those minima. Here we apply several statistics used in the study of phylogenetic trees to barrier trees that result from the energy landscapes of p-spin models. These statistics give information about the shape of these barrier trees, in particular about balance and symmetry. We then ask if they can be used to classify different types of landscapes, compare them with results obtained from random trees, and investigate the structure of subtrees of the barrier trees. We conclude that at least one of the used statistics is capable of distinguishing different types of landscapes, that the barrier trees from p-spin energy landscapes are quite different from random trees, and that subtrees of barrier trees do not reflect the overall tree structure, but their structure is correlated with their 'depth' in the tree

  19. Leaderless Transcripts and Small Proteins Are Common Features of the Mycobacterial Translational Landscape.

    Directory of Open Access Journals (Sweden)

    Scarlet S Shell

    2015-11-01

    Full Text Available RNA-seq technologies have provided significant insight into the transcription networks of mycobacteria. However, such studies provide no definitive information on the translational landscape. Here, we use a combination of high-throughput transcriptome and proteome-profiling approaches to more rigorously understand protein expression in two mycobacterial species. RNA-seq and ribosome profiling in Mycobacterium smegmatis, and transcription start site (TSS mapping and N-terminal peptide mass spectrometry in Mycobacterium tuberculosis, provide complementary, empirical datasets to examine the congruence of transcription and translation in the Mycobacterium genus. We find that nearly one-quarter of mycobacterial transcripts are leaderless, lacking a 5' untranslated region (UTR and Shine-Dalgarno ribosome-binding site. Our data indicate that leaderless translation is a major feature of mycobacterial genomes and is comparably robust to leadered initiation. Using translational reporters to systematically probe the cis-sequence requirements of leaderless translation initiation in mycobacteria, we find that an ATG or GTG at the mRNA 5' end is both necessary and sufficient. This criterion, together with our ribosome occupancy data, suggests that mycobacteria encode hundreds of small, unannotated proteins at the 5' ends of transcripts. The conservation of small proteins in both mycobacterial species tested suggests that some play important roles in mycobacterial physiology. Our translational-reporter system further indicates that mycobacterial leadered translation initiation requires a Shine Dalgarno site in the 5' UTR and that ATG, GTG, TTG, and ATT codons can robustly initiate translation. Our combined approaches provide the first comprehensive view of mycobacterial gene structures and their non-canonical mechanisms of protein expression.

  20. Practical dietary management of protein energy malnutrition in young children with cow's milk protein allergy.

    Science.gov (United States)

    Meyer, Rosan; Venter, Carina; Fox, Adam T; Shah, Neil

    2012-06-01

    Cow's milk protein allergy (CMPA) affects between 1.9 and 4.9% of infants and young children. This food allergy requires the complete elimination of cow's milk and its derivatives, impacting on nutritional status. The risk of having protein energy malnutrition (PEM) in children with CMPA has been well documented. In 2007, the World Health Organisation published guidelines on the dietary management of PEM, which has impacted on the recommendations and composition on specialist feeds for many chronic diseases, but not on CMPA. The main change in management of the child with PEM is the protein energy ratio and energy requirements. The ideal protein energy ratio lies between 8.9 and 11.5%, which would ensure a deposition of about 70% lean and 30% fat mass. In addition, for optimal catch-up growth between 5 and 10 g/kg/day, energy requirements should be between 105 and 126 kcal/kg/day. Although most current hypoallergenic formulas fall well within the recommendation for protein, there is a problem in achieving energy requirements. As a result, modular additions are often made, disturbing the protein energy ratio or feeds are concentrated, which impacts on osmolality. We therefore aimed to review current guidelines on PEM and how these can be applied in the management of the malnourished child with CMPA. © 2012 John Wiley & Sons A/S.

  1. Serum proteinase inhibitors and other serum proteins in protein-energy malnutrition

    NARCIS (Netherlands)

    Schelp, F.P.; Migasena, P.; Pongpaew, P.; SCHREURS W.H.P

    1977-01-01

    1. The concentrations of serum protein albumin, prealbumin and transferrin were determined in twenty-eight cases of protein-energy malnutrition (PEM) with infection, together with the levels of serum proteinase inhibitors (PI), alpha1-antitrypsin (AT), alpha1-antichymotrypsin (Ach),

  2. Protein energy malnutrition: analysis of admission and outcome ...

    African Journals Online (AJOL)

    Background: Protein energy malnutrition (PEM) is a common condition in our environment. The morbidity and mortality is still high. Method: A retrospective study of 136 children with PEM, aimed at evaluating the outcome of management of children with severe protein energy malnutrition in Ahmadu Bello University ...

  3. A Method for Extracting the Free Energy Surface and Conformational Dynamics of Fast-Folding Proteins from Single Molecule Photon Trajectories

    Science.gov (United States)

    2015-01-01

    Single molecule fluorescence spectroscopy holds the promise of providing direct measurements of protein folding free energy landscapes and conformational motions. However, fulfilling this promise has been prevented by technical limitations, most notably, the difficulty in analyzing the small packets of photons per millisecond that are typically recorded from individual biomolecules. Such limitation impairs the ability to accurately determine conformational distributions and resolve sub-millisecond processes. Here we develop an analytical procedure for extracting the conformational distribution and dynamics of fast-folding proteins directly from time-stamped photon arrival trajectories produced by single molecule FRET experiments. Our procedure combines the maximum likelihood analysis originally developed by Gopich and Szabo with a statistical mechanical model that describes protein folding as diffusion on a one-dimensional free energy surface. Using stochastic kinetic simulations, we thoroughly tested the performance of the method in identifying diverse fast-folding scenarios, ranging from two-state to one-state downhill folding, as a function of relevant experimental variables such as photon count rate, amount of input data, and background noise. The tests demonstrate that the analysis can accurately retrieve the original one-dimensional free energy surface and microsecond folding dynamics in spite of the sub-megahertz photon count rates and significant background noise levels of current single molecule fluorescence experiments. Therefore, our approach provides a powerful tool for the quantitative analysis of single molecule FRET experiments of fast protein folding that is also potentially extensible to the analysis of any other biomolecular process governed by sub-millisecond conformational dynamics. PMID:25988351

  4. Oil and Gas Development in Southwestern Wyoming - Energy Data and Services for the Wyoming Landscape Conservation Initiative (WLCI)

    Science.gov (United States)

    Biewick, Laura

    2009-01-01

    The purpose of this report is to explore current oil and gas energy development in the area encompassing the Wyoming Landscape Conservation Initiative. The Wyoming Landscape Conservation Initiative is a long-term science-based effort to ensure southwestern Wyoming's wildlife and habitat remain viable in areas facing development pressure. Wyoming encompasses some of the highest quality wildlife habitats in the Intermountain West. At the same time, this region is an important source of natural gas. Using Geographic Information System technology, energy data pertinent to the conservation decision-making process have been assembled to show historical oil and gas exploration and production in southwestern Wyoming. In addition to historical data, estimates of undiscovered oil and gas are included from the 2002 U.S. Geological Survey National Assessment of Oil and Gas in the Southwestern Wyoming Province. This report is meant to facilitate the integration of existing data with new knowledge and technologies to analyze energy resources development and to assist in habitat conservation planning. The well and assessment data can be accessed and shared among many different clients including, but not limited to, an online web-service for scientists and resource managers engaged in the Initiative.

  5. Ultra-processed foods, protein leverage and energy intake in the USA.

    Science.gov (United States)

    Martínez Steele, Euridice; Raubenheimer, David; Simpson, Stephen J; Baraldi, Larissa Galastri; Monteiro, Carlos A

    2018-01-01

    Experimental studies have shown that human macronutrient regulation minimizes variation in absolute protein intake and consequently energy intake varies passively with dietary protein density ('protein leverage'). According to the 'protein leverage hypothesis' (PLH), protein leverage interacts with a reduction in dietary protein density to drive energy overconsumption and obesity. Worldwide increase in consumption of ultra-processed foods (UPF) has been hypothesized to be an important determinant of dietary protein dilution, and consequently an ecological driving force of energy overconsumption and the obesity pandemic. The present study examined the relationships between dietary contribution of UPF, dietary proportional protein content and the absolute intakes of protein and energy. National representative cross-sectional study. National Health and Nutrition Examination Survey 2009-2010. Participants (n 9042) aged ≥2 years with at least one day of 24 h dietary recall data. We found a strong inverse relationship between consumption of UPF and dietary protein density, with mean protein content dropping from 18·2 to 13·3 % between the lowest and highest quintiles of dietary contribution of UPF. Consistent with the PLH, increase in the dietary contribution of UPF (previously shown to be inversely associated with protein density) was also associated with a rise in total energy intake, while absolute protein intake remained relatively constant. The protein-diluting effect of UPF might be one mechanism accounting for their association with excess energy intake. Reducing UPF contribution in the US diet may be an effective way to increase its dietary protein concentration and prevent excessive energy intake.

  6. potential for quality protein maize for reducing protein- energy

    African Journals Online (AJOL)

    ACSS

    social systems hampering QPM promotion and adoption and to identify ... affects growth and development. Protein- energy ... to purchase QPM seed leading to PEU reduction. Education ..... decision support framework “targetCSA”. Agricultural ...

  7. Shedding light on protein folding, structural and functional dynamics by single molecule studies

    DEFF Research Database (Denmark)

    Bavishi, Krutika; Hatzakis, Nikos

    2014-01-01

    property of a population, single molecule measurements offer observation and quantification of the abundance, lifetime and function of multiple protein states. They also permit the direct observation of the transient and rarely populated intermediates in the energy landscape that are typically averaged out...

  8. Ecological Functions of Landscapes

    Science.gov (United States)

    Kiryushin, V. I.

    2018-01-01

    Ecological functions of landscapes are considered a system of processes ensuring the development, preservation, and evolution of ecosystems and the biosphere as a whole. The concept of biogeocenosis can be considered a model that integrates biotic and environmental functions. The most general biogeocenotic functions specify the biodiversity, biotic links, self-organization, and evolution of ecosystems. Close interaction between biocenosis and the biotope (ecotope) is ensured by the continuous exchange of matter, energy, and information. Ecotope determines the biocenosis. The group of ecotopic functions includes atmospheric (gas exchange, heat exchange, hydroatmospheric, climate-forming), lithospheric (geodynamic, geophysical, and geochemical), hydrologic and hydrogeologic functions of landscape and ecotopic functions of soils. Bioecological functions emerge as a result of the biotope and ecotope interaction; these are the bioproductive, destructive, organoaccumulative, biochemical (gas, concentration, redox, biochemical, biopedological), pedogenetic, and energy functions

  9. PENGARUH BERBAGAI RASIO ENERGI PROTEIN PADA PAKAN ISO PROTEIN 30% TERHADAP KINERJA PERTUMBUHAN BENIH IKAN PATIN (Pangasius hypophthalmus

    Directory of Open Access Journals (Sweden)

    Mas Bayu Syamsunarno

    2011-04-01

    Full Text Available Tujuan percobaan ini adalah untuk menentukan rasio energi protein optimum yang menghasilkan pertumbuhan maksimum benih ikan patin (Pangasius hypophthalmus. Percobaan menggunakan 5 (lima pakan iso protein dengan rasio energi protein berbeda, yaitu: 8,5; 9,0; 9,5; 10,0; dan 10,5 kkal DE/g protein. Benih patin berukuran 1,84±0,02 g ditebar secara acak ke dalam 15 akuarium (50 cm x 40 cm x 35 cm dengan kepadatan 20 ekor per akuarium. Benih ikan patin tersebut diberi pakan uji dua kali sehari sekenyangnya (satiation selama 40 hari. Hasil percobaan menunjukkan bahwa kandungan protein tubuh tertinggi dihasilkan oleh pakan dengan rasio energi protein 9,0 kkal DE/g protein, sedangkan lemak tubuh terendah dicapai oleh perlakuan 8,5 kkal DE/g protein. Namun, protein karkas adalah sama untuk perlakuan 8,5–9,5 kkal DE/g protein dan kandungan lemak karkas terendah dicapai oleh 8,5 kkal DE/g protein. Konsumsi pakan, retensi protein, dan pertumbuhan tertinggi dihasilkan oleh pakan dengan rasio energi protein 9,0 kkal DE/g protein (P0,05. Oleh karena itu, kandungan optimum rasio energi protein 9,0 kkal DE/g protein memberikan pertumbuhan tertinggi pada benih ikan patin

  10. Crossover to potential energy landscape dominated dynamics in a model glass-forming liquid

    DEFF Research Database (Denmark)

    Schrøder, Thomas; Sastry, S.; Dyre, Jeppe

    2000-01-01

    An equilibrated model glass-forming liquid is studied by mapping successive configurations produced by molecular dynamics simulation onto a time series of inherent structures (local minima in the potential energy). Using this "inherent dynamics" approach we find direct numerical evidence for the ......An equilibrated model glass-forming liquid is studied by mapping successive configurations produced by molecular dynamics simulation onto a time series of inherent structures (local minima in the potential energy). Using this "inherent dynamics" approach we find direct numerical evidence...... for the long held view that below a crossover temperature, Tx, the liquid's dynamics can be separated into (i) vibrations around inherent structures and (ii) transitions between inherent structures [M. Goldstein, J. Chem. Phys. 51, 3728 (1969)], i.e., the dynamics become "dominated" by the potential energy...... landscape. In agreement with previous proposals, we find that Tx is within the vicinity of the mode-coupling critical temperature Tc. We further find that near Tx, transitions between inherent structures occur via cooperative, stringlike rearrangements of groups of particles moving distances substantially...

  11. Protein homology model refinement by large-scale energy optimization.

    Science.gov (United States)

    Park, Hahnbeom; Ovchinnikov, Sergey; Kim, David E; DiMaio, Frank; Baker, David

    2018-03-20

    Proteins fold to their lowest free-energy structures, and hence the most straightforward way to increase the accuracy of a partially incorrect protein structure model is to search for the lowest-energy nearby structure. This direct approach has met with little success for two reasons: first, energy function inaccuracies can lead to false energy minima, resulting in model degradation rather than improvement; and second, even with an accurate energy function, the search problem is formidable because the energy only drops considerably in the immediate vicinity of the global minimum, and there are a very large number of degrees of freedom. Here we describe a large-scale energy optimization-based refinement method that incorporates advances in both search and energy function accuracy that can substantially improve the accuracy of low-resolution homology models. The method refined low-resolution homology models into correct folds for 50 of 84 diverse protein families and generated improved models in recent blind structure prediction experiments. Analyses of the basis for these improvements reveal contributions from both the improvements in conformational sampling techniques and the energy function.

  12. Bioluminescence resonance energy transfer system for measuring dynamic protein-protein interactions in bacteria.

    Science.gov (United States)

    Cui, Boyu; Wang, Yao; Song, Yunhong; Wang, Tietao; Li, Changfu; Wei, Yahong; Luo, Zhao-Qing; Shen, Xihui

    2014-05-20

    Protein-protein interactions are important for virtually every biological process, and a number of elegant approaches have been designed to detect and evaluate such interactions. However, few of these methods allow the detection of dynamic and real-time protein-protein interactions in bacteria. Here we describe a bioluminescence resonance energy transfer (BRET) system based on the bacterial luciferase LuxAB. We found that enhanced yellow fluorescent protein (eYFP) accepts the emission from LuxAB and emits yellow fluorescence. Importantly, BRET occurred when LuxAB and eYFP were fused, respectively, to the interacting protein pair FlgM and FliA. Furthermore, we observed sirolimus (i.e., rapamycin)-inducible interactions between FRB and FKBP12 and a dose-dependent abolishment of such interactions by FK506, the ligand of FKBP12. Using this system, we showed that osmotic stress or low pH efficiently induced multimerization of the regulatory protein OmpR and that the multimerization induced by low pH can be reversed by a neutralizing agent, further indicating the usefulness of this system in the measurement of dynamic interactions. This method can be adapted to analyze dynamic protein-protein interactions and the importance of such interactions in bacterial processes such as development and pathogenicity. Real-time measurement of protein-protein interactions in prokaryotes is highly desirable for determining the roles of protein complex in the development or virulence of bacteria, but methods that allow such measurement are not available. Here we describe the development of a bioluminescence resonance energy transfer (BRET) technology that meets this need. The use of endogenous excitation light in this strategy circumvents the requirement for the sophisticated instrument demanded by standard fluorescence resonance energy transfer (FRET). Furthermore, because the LuxAB substrate decanal is membrane permeable, the assay can be performed without lysing the bacterial cells

  13. Reheating-volume measure in the string theory landscape

    International Nuclear Information System (INIS)

    Winitzki, Sergei

    2008-01-01

    I recently proposed the ''reheating-volume'' (RV) prescription as a possible solution to the measure problem in ''multiverse'' cosmology. The goal of this work is to extend the RV measure to scenarios involving bubble nucleation, such as the string theory landscape. In the spirit of the RV prescription, I propose to calculate the distribution of observable quantities in a landscape that is conditioned in probability to nucleate a finite total number of bubbles to the future of an initial bubble. A general formula for the relative number of bubbles of different types can be derived. I show that the RV measure is well defined and independent of the choice of the initial bubble type, as long as that type supports further bubble nucleation. Applying the RV measure to a generic landscape, I find that the abundance of Boltzmann brains is always negligibly small compared with the abundance of ordinary observers in the bubbles of the same type. As an illustration, I present explicit results for a toy landscape containing four vacuum states, and for landscapes with a single high-energy vacuum and a large number of low-energy vacua.

  14. Counteracting chemical chaperone effects on the single-molecule α-synuclein structural landscape.

    Science.gov (United States)

    Ferreon, Allan Chris M; Moosa, Mahdi Muhammad; Gambin, Yann; Deniz, Ashok A

    2012-10-30

    Protein structure and function depend on a close interplay between intrinsic folding energy landscapes and the chemistry of the protein environment. Osmolytes are small-molecule compounds that can act as chemical chaperones by altering the environment in a cellular context. Despite their importance, detailed studies on the role of these chemical chaperones in modulating structure and dimensions of intrinsically disordered proteins have been limited. Here, we used single-molecule Förster resonance energy transfer to test the counteraction hypothesis of counterbalancing effects between the protecting osmolyte trimethylamine-N-oxide (TMAO) and denaturing osmolyte urea for the case of α-synuclein, a Parkinson's disease-linked protein whose monomer exhibits significant disorder. The single-molecule experiments, which avoid complications from protein aggregation, do not exhibit clear solvent-induced cooperative protein transitions for these osmolytes, unlike results from previous studies on globular proteins. Our data demonstrate the ability of TMAO and urea to shift α-synuclein structures towards either more compact or expanded average dimensions. Strikingly, the experiments directly reveal that a 21 [urea][TMAO] ratio has a net neutral effect on the protein's dimensions, a result that holds regardless of the absolute osmolyte concentrations. Our findings shed light on a surprisingly simple aspect of the interplay between urea and TMAO on α-synuclein in the context of intrinsically disordered proteins, with potential implications for the biological roles of such chemical chaperones. The results also highlight the strengths of single-molecule experiments in directly probing the chemical physics of protein structure and disorder in more chemically complex environments.

  15. Integrated analysis of RNA-binding protein complexes using in vitro selection and high-throughput sequencing and sequence specificity landscapes (SEQRS).

    Science.gov (United States)

    Lou, Tzu-Fang; Weidmann, Chase A; Killingsworth, Jordan; Tanaka Hall, Traci M; Goldstrohm, Aaron C; Campbell, Zachary T

    2017-04-15

    RNA-binding proteins (RBPs) collaborate to control virtually every aspect of RNA function. Tremendous progress has been made in the area of global assessment of RBP specificity using next-generation sequencing approaches both in vivo and in vitro. Understanding how protein-protein interactions enable precise combinatorial regulation of RNA remains a significant problem. Addressing this challenge requires tools that can quantitatively determine the specificities of both individual proteins and multimeric complexes in an unbiased and comprehensive way. One approach utilizes in vitro selection, high-throughput sequencing, and sequence-specificity landscapes (SEQRS). We outline a SEQRS experiment focused on obtaining the specificity of a multi-protein complex between Drosophila RBPs Pumilio (Pum) and Nanos (Nos). We discuss the necessary controls in this type of experiment and examine how the resulting data can be complemented with structural and cell-based reporter assays. Additionally, SEQRS data can be integrated with functional genomics data to uncover biological function. Finally, we propose extensions of the technique that will enhance our understanding of multi-protein regulatory complexes assembled onto RNA. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Peptide-chaperone-directed transdermal protein delivery requires energy.

    Science.gov (United States)

    Ruan, Renquan; Jin, Peipei; Zhang, Li; Wang, Changli; Chen, Chuanjun; Ding, Weiping; Wen, Longping

    2014-11-03

    The biologically inspired transdermal enhanced peptide TD1 has been discovered to specifically facilitate transdermal delivery of biological macromolecules. However, the biological behavior of TD1 has not been fully defined. In this study, we find that energy is required for the TD1-mediated transdermal protein delivery through rat and human skins. Our results show that the permeation activity of TD1-hEGF, a fusion protein composed of human epidermal growth factor (hEGF) and the TD1 sequence connected with a glycine-serine linker (GGGGS), can be inhibited by the energy inhibitor, rotenone or oligomycin. In addition, adenosine triphosphate (ATP), the essential energetic molecule in organic systems, can effectively facilitate the TD1 directed permeation of the protein-based drug into the skin in a dose-dependent fashion. Our results here demonstrate a novel energy-dependent permeation process during the TD1-mediated transdermal protein delivery that could be valuable for the future development of promising new transdermal drugs.

  17. Landscape equivalent of the shoving model

    DEFF Research Database (Denmark)

    Dyre, Jeppe; Olsen, Niels Boye

    2004-01-01

    It is shown that the shoving model expression for the average relaxation time of viscous liquids, according to which the activation energy is proportional to the instantaneous shear modulus, follows largely from a classical "landscape" estimation of barrier heights from curvature at energy minima...

  18. Quantitative analysis of the publishing landscape in High-Energy Physics

    CERN Document Server

    Mele, S; Vigen, Jens; Yeomans, Joanne

    2006-01-01

    World-wide collaboration in high-energy physics (HEP) is a tradition which dates back several decades, with scientific publications mostly coauthored by scientists from different countries. This coauthorship phenomenon makes it difficult to identify precisely the "share" of each country in HEP scientific production. One year's worth of HEP scientific articles published in peer-reviewed journals is analysed and their authors are uniquely assigned to countries. This method allows the first correct estimation on a pro rata basis of the share of HEP scientific publishing among several countries and institutions. The results provide an interesting insight into the geographical collaborative patterns of the HEP community. The HEP publishing landscape is further analysed to provide information on the journals favoured by the HEP community and on the geographical variation of their author bases. These results provide quantitative input to the ongoing debate on the possible transition of HEP publishing to an Open Acce...

  19. Effect of balanced protein energy supplementation during pregnancy on birth outcomes

    Directory of Open Access Journals (Sweden)

    Bhutta Zulfiqar A

    2011-04-01

    Full Text Available Abstract Background The nutritional status of the mother prior to and during pregnancy plays a vital role in fetal growth and development, and maternal undernourishment may lead to adverse perinatal outcomes including intrauterine growth restriction (IUGR. Several macronutrient interventions had been proposed for adequate protein and energy supplementation during pregnancy. The objective of this paper was to review the effect of balanced protein energy supplementation during pregnancy on birth outcomes. This paper is a part of a series of reviews undertaken for getting estimates of effectiveness of an intervention for input to Lives Saved Tool (LiST model. Methods A literature search was conducted on PubMed, Cochrane Library and WHO regional data bases to identify randomized trials (RCTs and quasi RCTs that evaluated the impact of balanced protein energy supplementation in pregnancy. Balanced protein energy supplementation was defined as nutritional supplementation during pregnancy in which proteins provided less than 25% of the total energy content. Those studies were excluded in which the main intervention was dietary advice to pregnant women for increase in protein energy intake, high protein supplementation (i.e. supplementation in which protein provides at least 25% of total energy content, isocaloric protein supplementation (where protein replaces an equal quantity of non-protein energy content, or low energy diet to pregnant women who are either overweight or who exhibit high weight gain earlier in gestation. The primary outcomes were incidence of small for gestational age (SGA birth, mean birth weight and neonatal mortality. Quality of evidence was evaluated according to the Child Health Epidemiology Reference group (CHERG adaptation of Grading of Recommendations Assessment, Development and Evaluation (GRADE criteria. Results The final number of studies included in our review was eleven comprising of both RCTs and quasi-RCTs. Our meta

  20. Our Common Landscapes For The Future

    DEFF Research Database (Denmark)

    Brandt, Jesper

    2017-01-01

    Foreword for Marc Antrop and Veerle van Eetvelde: Landscape Perspectives – The Holistic Nature of Landscapes Our common landscapes for the future by Jesper Brandt The solution of the ecological crisis through a transformation towards sustainable development is the most urgent challenge in our time....... It is not just a question of CO2 and conversion toward renewable energy. The reestablishment and conscious development of our common landscapes at all spatial scales for the combined benefits of biodiversity, our cultural heritage and the preservation and development of ecosystem services will probably...... be the most comprehensive and necessary social task in the future, if a conversion towards a sustainable development shall succeed in due time. This is so because it will be necessary to ensure that the potential material wealth of modern society will be transformed into a good, fruitful and healthy life...

  1. Describing intrinsically disordered proteins at atomic resolution by NMR

    International Nuclear Information System (INIS)

    Ringkjobing Jensen, Malene; Blackledge, Martin; Ruigrok, Rob WH

    2013-01-01

    There is growing interest in the development of physical methods to study the conformational behaviour and biological activity of intrinsically disordered proteins (IDPs). In this review recent advances in the elucidation of quantitative descriptions of disordered proteins from nuclear magnetic resonance spectroscopy are presented. Ensemble approaches are particularly well adapted to map the conformational energy landscape sampled by the protein at atomic resolution. Significant advances in development of calibrated approaches to the statistical representation of the conformational behaviour of IDPs are presented, as well as applications to some biologically important systems where disorder plays a crucial role. (authors)

  2. Counteracting chemical chaperone effects on the single-molecule α-synuclein structural landscape

    Science.gov (United States)

    Ferreon, Allan Chris M.; Moosa, Mahdi Muhammad; Deniz, Ashok A.

    2012-01-01

    Protein structure and function depend on a close interplay between intrinsic folding energy landscapes and the chemistry of the protein environment. Osmolytes are small-molecule compounds that can act as chemical chaperones by altering the environment in a cellular context. Despite their importance, detailed studies on the role of these chemical chaperones in modulating structure and dimensions of intrinsically disordered proteins have been limited. Here, we used single-molecule Förster resonance energy transfer to test the counteraction hypothesis of counterbalancing effects between the protecting osmolyte trimethylamine-N-oxide (TMAO) and denaturing osmolyte urea for the case of α-synuclein, a Parkinson’s disease-linked protein whose monomer exhibits significant disorder. The single-molecule experiments, which avoid complications from protein aggregation, do not exhibit clear solvent-induced cooperative protein transitions for these osmolytes, unlike results from previous studies on globular proteins. Our data demonstrate the ability of TMAO and urea to shift α-synuclein structures towards either more compact or expanded average dimensions. Strikingly, the experiments directly reveal that a 2∶1 [urea]∶[TMAO] ratio has a net neutral effect on the protein’s dimensions, a result that holds regardless of the absolute osmolyte concentrations. Our findings shed light on a surprisingly simple aspect of the interplay between urea and TMAO on α-synuclein in the context of intrinsically disordered proteins, with potential implications for the biological roles of such chemical chaperones. The results also highlight the strengths of single-molecule experiments in directly probing the chemical physics of protein structure and disorder in more chemically complex environments. PMID:22826265

  3. Energie- en eiwitbehoefte van biologisch gehouden pluimvee = Energy and protein requirements of organic housed poultry

    NARCIS (Netherlands)

    Knegsel, van A.T.M.; Krimpen, van M.M.

    2008-01-01

    In this literature review, the physiological basis for possible differences in energy and protein requirements of organic versus conventional poultry is investigated. Energy need for maintenance of organic housed poultry seems to be increased, whereas protein requirements might not differ between

  4. Flowscapes : Infrastructure as landscape, landscape as infrastructure. Graduation Lab Landscape Architecture 2012/2013

    NARCIS (Netherlands)

    Nijhuis, S.; Jauslin, D.; De Vries, C.

    2012-01-01

    Flowscapes explores infrastructure as a type of landscape and landscape as a type of infrastructure, and is focused on landscape architectonic design of transportation-, green- and water infrastructures. These landscape infrastructures are considered armatures for urban and rural development. With

  5. Frustration-guided motion planning reveals conformational transitions in proteins.

    Science.gov (United States)

    Budday, Dominik; Fonseca, Rasmus; Leyendecker, Sigrid; van den Bedem, Henry

    2017-10-01

    Proteins exist as conformational ensembles, exchanging between substates to perform their function. Advances in experimental techniques yield unprecedented access to structural snapshots of their conformational landscape. However, computationally modeling how proteins use collective motions to transition between substates is challenging owing to a rugged landscape and large energy barriers. Here, we present a new, robotics-inspired motion planning procedure called dCC-RRT that navigates the rugged landscape between substates by introducing dynamic, interatomic constraints to modulate frustration. The constraints balance non-native contacts and flexibility, and instantaneously redirect the motion towards sterically favorable conformations. On a test set of eight proteins determined in two conformations separated by, on average, 7.5 Å root mean square deviation (RMSD), our pathways reduced the Cα atom RMSD to the goal conformation by 78%, outperforming peer methods. We then applied dCC-RRT to examine how collective, small-scale motions of four side-chains in the active site of cyclophilin A propagate through the protein. dCC-RRT uncovered a spatially contiguous network of residues linked by steric interactions and collective motion connecting the active site to a recently proposed, non-canonical capsid binding site 25 Å away, rationalizing NMR and multi-temperature crystallography experiments. In all, dCC-RRT can reveal detailed, all-atom molecular mechanisms for small and large amplitude motions. Source code and binaries are freely available at https://github.com/ExcitedStates/KGS/. © 2017 Wiley Periodicals, Inc.

  6. Alternating access mechanisms of LeuT-fold transporters: trailblazing towards the promised energy landscapes.

    Science.gov (United States)

    Kazmier, Kelli; Claxton, Derek P; Mchaourab, Hassane S

    2017-08-01

    Secondary active transporters couple the uphill translocation of substrates to electrochemical ion gradients. Transporter conformational motion, generically referred to as alternating access, enables a central ligand binding site to change its orientation relative to the membrane. Here we review themes of alternating access and the transduction of ion gradient energy to power this process in the LeuT-fold class of transporters where crystallographic, computational and spectroscopic approaches have converged to yield detailed models of transport cycles. Specifically, we compare findings for the Na + -coupled amino acid transporter LeuT and the Na + -coupled hydantoin transporter Mhp1. Although these studies have illuminated multiple aspects of transporter structures and dynamics, a number of questions remain unresolved that so far hinder understanding transport mechanisms in an energy landscape perspective. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Impact of hydrodynamic interactions on protein folding rates depends on temperature

    Science.gov (United States)

    Zegarra, Fabio C.; Homouz, Dirar; Eliaz, Yossi; Gasic, Andrei G.; Cheung, Margaret S.

    2018-03-01

    We investigated the impact of hydrodynamic interactions (HI) on protein folding using a coarse-grained model. The extent of the impact of hydrodynamic interactions, whether it accelerates, retards, or has no effect on protein folding, has been controversial. Together with a theoretical framework of the energy landscape theory (ELT) for protein folding that describes the dynamics of the collective motion with a single reaction coordinate across a folding barrier, we compared the kinetic effects of HI on the folding rates of two protein models that use a chain of single beads with distinctive topologies: a 64-residue α /β chymotrypsin inhibitor 2 (CI2) protein, and a 57-residue β -barrel α -spectrin Src-homology 3 domain (SH3) protein. When comparing the protein folding kinetics simulated with Brownian dynamics in the presence of HI to that in the absence of HI, we find that the effect of HI on protein folding appears to have a "crossover" behavior about the folding temperature. This means that at a temperature greater than the folding temperature, the enhanced friction from the hydrodynamic solvents between the beads in an unfolded configuration results in lowered folding rate; conversely, at a temperature lower than the folding temperature, HI accelerates folding by the backflow of solvent toward the folded configuration of a protein. Additionally, the extent of acceleration depends on the topology of a protein: for a protein like CI2, where its folding nucleus is rather diffuse in a transition state, HI channels the formation of contacts by favoring a major folding pathway in a complex free energy landscape, thus accelerating folding. For a protein like SH3, where its folding nucleus is already specific and less diffuse, HI matters less at a temperature lower than the folding temperature. Our findings provide further theoretical insight to protein folding kinetic experiments and simulations.

  8. Do geographically isolated wetlands influence landscape functions?

    OpenAIRE

    Cohen, Matthew J.; Creed, Irena F.; Alexander, Laurie; Basu, Nandita B.; Calhoun, Aram J. K.; Craft, Christopher; D’Amico, Ellen; DeKeyser, Edward; Fowler, Laurie; Golden, Heather E.; Jawitz, James W.; Kalla, Peter; Kirkman, L. Katherine; Lane, Charles R.; Lang, Megan

    2016-01-01

    Geographically isolated wetlands (GIWs), those surrounded by uplands, exchange materials, energy, and organisms with other elements in hydrological and habitat networks, contributing to landscape functions, such as flow generation, nutrient and sediment retention, and biodiversity support. GIWs constitute most of the wetlands in many North American landscapes, provide a disproportionately large fraction of wetland edges where many functions are enhanced, and form complexes with other water bo...

  9. Landscape metrics application in ecological and visual landscape assessment

    Directory of Open Access Journals (Sweden)

    Gavrilović Suzana

    2017-01-01

    Full Text Available The development of landscape-ecological approach application in spatial planning provides exact theoretical and empirical evidence for monitoring ecological consequences of natural and/or anthropogenic factors, particularly changes in spatial structures caused by them. Landscape pattern which feature diverse landscape values is the holder of the unique landscape character at different spatial levels and represents a perceptual domain for its users. Using the landscape metrics, the parameters of landscape composition and configuration are mathematical algorithms that quantify the specific spatial characteristics used for interpretation of landscape features and processes (physical and ecological aspect, as well as forms (visual aspect and the meaning (cognitive aspect of the landscape. Landscape metrics has been applied mostly in the ecological and biodiversity assessments as well as in the determination of the level of structural change of landscape, but more and more applied in the assessment of the visual character of the landscape. Based on a review of relevant literature, the aim of this work is to show the main trends of landscape metrics within the aspect of ecological and visual assessments. The research methodology is based on the analysis, classification and systematization of the research studies published from 2000 to 2016, where the landscape metrics is applied: (1 the analysis of landscape pattern and its changes, (2 the analysis of biodiversity and habitat function and (3 a visual landscape assessment. By selecting representative metric parameters for the landscape composition and configuration, for each category is formed the basis for further landscape metrics research and application for the integrated ecological and visual assessment of the landscape values. Contemporary conceptualization of the landscape is seen holistically, and the future research should be directed towards the development of integrated landscape assessment

  10. Effect of constant digestible protein intake and varying digestible energy levels on energy and protein utilization in Nile tilapia

    NARCIS (Netherlands)

    Haidar, M.N.; Bleeker, S.; Heinsbroek, L.T.N.; Schrama, J.W.

    2018-01-01

    In literature, the variability in the estimated optimal digestible protein to digestible energy ratio (DP/DE) is high. The present study aimed to estimate the optimal DP/DE ratio in Nile tilapia (Oreochromis niloticus) using different criteria (performance, energy and nitrogen balances parameters).

  11. Bacterial growth laws reflect the evolutionary importance of energy efficiency.

    Science.gov (United States)

    Maitra, Arijit; Dill, Ken A

    2015-01-13

    We are interested in the balance of energy and protein synthesis in bacterial growth. How has evolution optimized this balance? We describe an analytical model that leverages extensive literature data on growth laws to infer the underlying fitness landscape and to draw inferences about what evolution has optimized in Escherichia coli. Is E. coli optimized for growth speed, energy efficiency, or some other property? Experimental data show that at its replication speed limit, E. coli produces about four mass equivalents of nonribosomal proteins for every mass equivalent of ribosomes. This ratio can be explained if the cell's fitness function is the the energy efficiency of cells under fast growth conditions, indicating a tradeoff between the high energy costs of ribosomes under fast growth and the high energy costs of turning over nonribosomal proteins under slow growth. This model gives insight into some of the complex nonlinear relationships between energy utilization and ribosomal and nonribosomal production as a function of cell growth conditions.

  12. Equilibrium simulations of proteins using molecular fragment replacement and NMR chemical shifts.

    Science.gov (United States)

    Boomsma, Wouter; Tian, Pengfei; Frellsen, Jes; Ferkinghoff-Borg, Jesper; Hamelryck, Thomas; Lindorff-Larsen, Kresten; Vendruscolo, Michele

    2014-09-23

    Methods of protein structure determination based on NMR chemical shifts are becoming increasingly common. The most widely used approaches adopt the molecular fragment replacement strategy, in which structural fragments are repeatedly reassembled into different complete conformations in molecular simulations. Although these approaches are effective in generating individual structures consistent with the chemical shift data, they do not enable the sampling of the conformational space of proteins with correct statistical weights. Here, we present a method of molecular fragment replacement that makes it possible to perform equilibrium simulations of proteins, and hence to determine their free energy landscapes. This strategy is based on the encoding of the chemical shift information in a probabilistic model in Markov chain Monte Carlo simulations. First, we demonstrate that with this approach it is possible to fold proteins to their native states starting from extended structures. Second, we show that the method satisfies the detailed balance condition and hence it can be used to carry out an equilibrium sampling from the Boltzmann distribution corresponding to the force field used in the simulations. Third, by comparing the results of simulations carried out with and without chemical shift restraints we describe quantitatively the effects that these restraints have on the free energy landscapes of proteins. Taken together, these results demonstrate that the molecular fragment replacement strategy can be used in combination with chemical shift information to characterize not only the native structures of proteins but also their conformational fluctuations.

  13. Analyzing high resolution topography for advancing the understanding of mass and energy transfer through landscapes: A review

    Science.gov (United States)

    Passaiacquaa, Paola; Belmont, Patrick; Staley, Dennis M.; Simley, Jeffery; Arrowsmith, J. Ramon; Bode, Collin A.; Crosby, Christopher; DeLong, Stephen; Glenn, Nancy; Kelly, Sara; Lague, Dimitri; Sangireddy, Harish; Schaffrath, Keelin; Tarboton, David; Wasklewicz, Thad; Wheaton, Joseph

    2015-01-01

    The study of mass and energy transfer across landscapes has recently evolved to comprehensive considerations acknowledging the role of biota and humans as geomorphic agents, as well as the importance of small-scale landscape features. A contributing and supporting factor to this evolution is the emergence over the last two decades of technologies able to acquire high resolution topography (HRT) (meter and sub-meter resolution) data. Landscape features can now be captured at an appropriately fine spatial resolution at which surface processes operate; this has revolutionized the way we study Earth-surface processes. The wealth of information contained in HRT also presents considerable challenges. For example, selection of the most appropriate type of HRT data for a given application is not trivial. No definitive approach exists for identifying and filtering erroneous or unwanted data, yet inappropriate filtering can create artifacts or eliminate/distort critical features. Estimates of errors and uncertainty are often poorly defined and typically fail to represent the spatial heterogeneity of the dataset, which may introduce bias or error for many analyses. For ease of use, gridded products are typically preferred rather than the more information-rich point cloud representations. Thus many users take advantage of only a fraction of the available data, which has furthermore been subjected to a series of operations often not known or investigated by the user. Lastly, standard HRT analysis work-flows are yet to be established for many popular HRT operations, which has contributed to the limited use of point cloud data.In this review, we identify key research questions relevant to the Earth-surface processes community within the theme of mass and energy transfer across landscapes and offer guidance on how to identify the most appropriate topographic data type for the analysis of interest. We describe the operations commonly performed from raw data to raster products and

  14. The energy landscape of glassy dynamics on the amorphous hafnium diboride surface

    International Nuclear Information System (INIS)

    Nguyen, Duc; Girolami, Gregory S.; Mallek, Justin; Cloud, Andrew N.; Abelson, John R.; Lyding, Joseph; Gruebele, Martin

    2014-01-01

    Direct visualization of the dynamics of structural glasses and amorphous solids on the sub-nanometer scale provides rich information unavailable from bulk or conventional single molecule techniques. We study the surface of hafnium diboride, a conductive ultrahigh temperature ceramic material that can be grown in amorphous films. Our scanning tunneling movies have a second-to-hour dynamic range and single-point current measurements extend that to the millisecond-to-minute time scale. On the a-HfB 2 glass surface, two-state hopping of 1–2 nm diameter cooperatively rearranging regions or “clusters” occurs from sub-milliseconds to hours. We characterize individual clusters in detail through high-resolution (<0.5 nm) imaging, scanning tunneling spectroscopy and voltage modulation, ruling out individual atoms, diffusing adsorbates, or pinned charges as the origin of the observed two-state hopping. Smaller clusters are more likely to hop, larger ones are more likely to be immobile. HfB 2 has a very high bulk glass transition temperature T g , and we observe no three-state hopping or sequential two-state hopping previously seen on lower T g glass surfaces. The electronic density of states of clusters does not change when they hop up or down, allowing us to calibrate an accurate relative z-axis scale. By directly measuring and histogramming single cluster vertical displacements, we can reconstruct the local free energy landscape of individual clusters, complete with activation barrier height, a reaction coordinate in nanometers, and the shape of the free energy landscape basins between which hopping occurs. The experimental images are consistent with the compact shape of α-relaxors predicted by random first order transition theory, whereas the rapid hopping rate, even taking less confined motion at the surface into account, is consistent with β-relaxations. We make a proposal of how “mixed” features can show up in surface dynamics of glasses

  15. Conformational dynamics of amyloid proteins at the aqueous interface

    Science.gov (United States)

    Armbruster, Matthew; Horst, Nathan; Aoki, Brendy; Malik, Saad; Soto, Patricia

    2013-03-01

    Amyloid proteins is a class of proteins that exhibit distinct monomeric and oligomeric conformational states hallmark of deleterious neurological diseases for which there are not yet cures. Our goal is to examine the extent of which the aqueous/membrane interface modulates the folding energy landscape of amyloid proteins. To this end, we probe the dynamic conformational ensemble of amyloids (monomer prion protein and Alzheimer's Ab protofilaments) interacting with model bilayers. We will present the results of our coarse grain molecular modeling study in terms of the existence of preferential binding spots of the amyloid to the bilayer and the response of the bilayer to the interaction with the amyloid. NSF Nebraska EPSCoR First Award

  16. Protein energy malnutrition predicts complications in liver cirrhosis.

    Science.gov (United States)

    Huisman, Ellen J; Trip, Evelien J; Siersema, Peter D; van Hoek, Bart; van Erpecum, Karel J

    2011-11-01

    Protein energy malnutrition frequently occurs in liver cirrhosis. Hand-grip strength according to Jamar is most reliable to predict protein energy malnutrition. We aimed to determine whether protein energy malnutrition affects complication risk. In 84 cirrhotics, baseline nutritional state was determined and subsequent complications prospectively assessed. Influence of potentially relevant factors including malnutrition (by Jamar hand-grip strength) on complication rates were evaluated with univariate analysis. Effect of malnutrition was subsequently evaluated by multivariate logistic regression with adjustment for possible confounders. Underlying causes of cirrhosis were viral hepatitis in 31%, alcohol in 26%, and other in 43%. Baseline Child-Pugh (CP) class was A, B, or C in 58, 35, and 7%, respectively. Energy and protein intake decreased significantly with increasing CP class, with shift from proteins to carbohydrates. At baseline, according to Jamar hand-grip strength, malnutrition occurred in 67% (n=56). Malnutrition was associated with older age and higher CP class (CP class A 57%, B 79%, C 100%) but not with underlying disease or comorbidity. Complications occurred in 18 and 48% in well-nourished and malnourished patients, respectively, (P=0.007) during 13 ± 6 months follow-up. In multivariate analysis, malnutrition was an independent predictor of complications, after correcting for comorbidity, age, and CP score (adjusted odds ratio 4.230; 95% confidence interval 1.090-16.422; P=0.037). In univariate analysis, mortality (4 vs. 18%; P=0.1) tended to be worse in malnourished patients, but this trend was lost in multivariate analysis. Malnutrition is an independent predictor of complications in cirrhosis.

  17. Landscape Studio

    DEFF Research Database (Denmark)

    Hansen, Peter Lundsgaard

    2017-01-01

    Landscape studio documents is the biography of the method 'design conversation' and contributes to the way we work with landscapes. The blog communicates renewed landscape didactics and leads to the innovation of design practices.......Landscape studio documents is the biography of the method 'design conversation' and contributes to the way we work with landscapes. The blog communicates renewed landscape didactics and leads to the innovation of design practices....

  18. Possible Biochemical Markers in Protein-Energy Malnutrition and ...

    African Journals Online (AJOL)

    This study was carried out to determine possible biochemical markers in children suffering from Plasmodium falciparum malaria and Protein-Energy Malnutrition in a Hospital setting in Western Kenya. Spectrophotometric assays of selected biochemical parameters namely, albumin, total proteins, glucose, glutamate ...

  19. Observing Protein & Energy Nutrition (OPEN) Study

    Science.gov (United States)

    The Observing Protein and Energy Nutrition (OPEN) Study was designed to assess dietary measurement error by comparing results from self-reported dietary intake data with four dietary biomarkers: doubly labeled water and urinary nitrogen, sodium, and potassium.

  20. Knotting and unknotting proteins in the chaperonin cage: Effects of the excluded volume.

    Directory of Open Access Journals (Sweden)

    Szymon Niewieczerzal

    Full Text Available Molecular dynamics simulations are used to explore the effects of chaperonin-like cages on knotted proteins with very low sequence similarity, different depths of a knot but with a similar fold, and the same type of topology. The investigated proteins are VirC2, DndE and MJ0366 with two depths of a knot. A comprehensive picture how encapsulation influences folding rates is provided based on the analysis of different cage sizes and temperature conditions. Neither of these two effects with regard to knotted proteins has been studied by means of molecular dynamics simulations with coarse-grained structure-based models before. We show that encapsulation in a chaperonin is sufficient to self-tie and untie small knotted proteins (VirC2, DndE, for which the equilibrium process is not accessible in the bulk solvent. Furthermore, we find that encapsulation reduces backtracking that arises from the destabilisation of nucleation sites, smoothing the free energy landscape. However, this effect can also be coupled with temperature rise. Encapsulation facilitates knotting at the early stage of folding and can enhance an alternative folding route. Comparison to unknotted proteins with the same fold shows directly how encapsulation influences the free energy landscape. In addition, we find that as the size of the cage decreases, folding times increase almost exponentially in a certain range of cage sizes, in accordance with confinement theory and experimental data for unknotted proteins.

  1. Landscape impact assessment of wind farm development in Dyfed

    International Nuclear Information System (INIS)

    Blandford, C.; White, S.; Garrad, A.D.; Morgan, C.A.

    1992-01-01

    Chris Blandford Associates, in association with Garrad Hassan and Partners, was commissioned to carry out a landscape impact assessment of wind turbine development in Dyfed. The study aims to identify those areas in Dyfed where, in terms of landscape impact, local authorities might seek either to exclude or encourage wind turbine development; provide guidelines to assist local authorities in judging the impact of wind turbine developments on the landscape; provide a basis and framework for the preparation of planning policy guidelines for acceptable wind turbine and wind farm developments in Dyfed. The study context reviews current Government energy and planning policies for the encouragement of wind turbine developments, as set out in the ''non-fossil fuel obligation'' and the draft planning policy guidance note for renewable energy published last December. (author)

  2. Liver Function Status in some Nigerian Children with Protein Energy ...

    African Journals Online (AJOL)

    Objective: To ascertain functional status of the liver in Nigeria Children with Protein energy malnutrition. Materials and Methods: Liver function tests were performed on a total of 88 children with protein energy malnutrition (PEM). These were compared with 22 apparently well-nourished children who served as controls.

  3. Reduction of erythroid progenitors in protein-energy malnutrition.

    Science.gov (United States)

    Borelli, Primavera; Blatt, Solange; Pereira, Juliana; de Maurino, Beatriz Beutler; Tsujita, Maristela; de Souza, Ana Cristina; Xavier, José Guilherme; Fock, Ricardo Ambrósio

    2007-02-01

    Protein-energy malnutrition is a syndrome in which anaemia together with multivitamin and mineral deficiency may be present. The pathophysiological mechanisms involved have not, however, yet been completely elucidated. The aim of the present study was to evaluate the pathophysiological processes that occur in this anaemia in animals that were submitted to protein-energy malnutrition, in particular with respect to Fe concentration and the proliferative activity of haemopoietic cells. For this, histological, histochemical, cell culture and immunophenotyping techniques were used. Two-month-old male Swiss mice were submitted to protein-energy malnutrition with a low-protein diet (20 g/kg) compared with control diet (400 g/kg). When the experimental group had attained a 20 % loss of their original body weight, the animals from both groups received, intravenously, 20 IU erythropoietin every other day for 14 d. Malnourished animals showed a decrease in red blood cells, Hb concentration and reticulocytopenia, as well as severe bone marrow and splenic atrophy. The results for serum Fe, total Fe-binding capacity, transferrin and erythropoietin in malnourished animals were no different from those of the control animals. Fe reserves in the spleen, liver and bone marrow were found to be greater in the malnourished animals. The mixed colony-forming unit assays revealed a smaller production of granulocyte-macrophage colony-forming units, erythroid burst-forming units, erythroid colony-forming units and CD45, CD117, CD119 and CD71 expression in the bone marrow and spleen cells of malnourished animals. These findings suggest that, in this protein-energy malnutrition model, anaemia is not caused by Fe deficiency or erythropoietin deficiency, but is a result of ineffective erythropoiesis.

  4. Buildings Interoperability Landscape

    Energy Technology Data Exchange (ETDEWEB)

    Hardin, Dave [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Stephan, Eric G. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Wang, Weimin [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Corbin, Charles D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Widergren, Steven E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-12-31

    Through its Building Technologies Office (BTO), the United States Department of Energy’s Office of Energy Efficiency and Renewable Energy (DOE-EERE) is sponsoring an effort to advance interoperability for the integration of intelligent buildings equipment and automation systems, understanding the importance of integration frameworks and product ecosystems to this cause. This is important to BTO’s mission to enhance energy efficiency and save energy for economic and environmental purposes. For connected buildings ecosystems of products and services from various manufacturers to flourish, the ICT aspects of the equipment need to integrate and operate simply and reliably. Within the concepts of interoperability lie the specification, development, and certification of equipment with standards-based interfaces that connect and work. Beyond this, a healthy community of stakeholders that contribute to and use interoperability work products must be developed. On May 1, 2014, the DOE convened a technical meeting to take stock of the current state of interoperability of connected equipment and systems in buildings. Several insights from that meeting helped facilitate a draft description of the landscape of interoperability for connected buildings, which focuses mainly on small and medium commercial buildings. This document revises the February 2015 landscape document to address reviewer comments, incorporate important insights from the Buildings Interoperability Vision technical meeting, and capture thoughts from that meeting about the topics to be addressed in a buildings interoperability vision. In particular, greater attention is paid to the state of information modeling in buildings and the great potential for near-term benefits in this area from progress and community alignment.

  5. Coarse-grained versus atomistic simulations : realistic interaction free energies for real proteins

    NARCIS (Netherlands)

    May, Ali; Pool, René; van Dijk, Erik; Bijlard, Jochem; Abeln, Sanne; Heringa, Jaap; Feenstra, K Anton

    2014-01-01

    MOTIVATION: To assess whether two proteins will interact under physiological conditions, information on the interaction free energy is needed. Statistical learning techniques and docking methods for predicting protein-protein interactions cannot quantitatively estimate binding free energies. Full

  6. Coarse-grained versus atomistic simulations: realistic interaction free energies for real proteins

    NARCIS (Netherlands)

    May, A.; Pool, R.; van Dijk, E.; Bijlard, J.; Abeln, S.; Heringa, J.; Feenstra, K.A.

    2014-01-01

    MOTIVATION: To assess whether two proteins will interact under physiological conditions, information on the interaction free energy is needed. Statistical learning techniques and docking methods for predicting protein-protein interactions cannot quantitatively estimate binding free energies. Full

  7. Protein energy malnutrition increases arginase activity in monocytes and macrophages.

    Science.gov (United States)

    Corware, Karina; Yardley, Vanessa; Mack, Christopher; Schuster, Steffen; Al-Hassi, Hafid; Herath, Shanthi; Bergin, Philip; Modolell, Manuel; Munder, Markus; Müller, Ingrid; Kropf, Pascale

    2014-01-01

    Protein energy malnutrition is commonly associated with immune dysfunctions and is a major factor in susceptibility to infectious diseases. In this study, we evaluated the impact of protein energy malnutrition on the capacity of monocytes and macrophages to upregulate arginase, an enzyme associated with immunosuppression and increased pathogen replication. Our results show that monocytes and macrophages are significantly increased in the bone marrow and blood of mice fed on a protein low diet. No alteration in the capacity of bone marrow derived macrophages isolated from malnourished mice to phagocytose particles, to produce the microbicidal molecule nitric oxide and to kill intracellular Leishmania parasites was detected. However, macrophages and monocytes from malnourished mice express significantly more arginase both in vitro and in vivo. Using an experimental model of visceral leishmaniasis, we show that following protein energy malnutrition, the increased parasite burden measured in the spleen of these mice coincided with increased arginase activity and that macrophages provide a more permissive environment for parasite growth. Taken together, these results identify a novel mechanism in protein energy malnutrition that might contributes to increased susceptibility to infectious diseases by upregulating arginase activity in myeloid cells.

  8. DNA exit ramps are revealed in the binding landscapes obtained from simulations in helical coordinates.

    Directory of Open Access Journals (Sweden)

    Ignacia Echeverria

    2015-02-01

    Full Text Available DNA molecules are highly charged semi-flexible polymers that are involved in a wide variety of dynamical processes such as transcription and replication. Characterizing the binding landscapes around DNA molecules is essential to understanding the energetics and kinetics of various biological processes. We present a curvilinear coordinate system that fully takes into account the helical symmetry of a DNA segment. The latter naturally allows to characterize the spatial organization and motions of ligands tracking the minor or major grooves, in a motion reminiscent of sliding. Using this approach, we performed umbrella sampling (US molecular dynamics (MD simulations to calculate the three-dimensional potentials of mean force (3D-PMFs for a Na+ cation and for methyl guanidinium, an arginine analog. The computed PMFs show that, even for small ligands, the free energy landscapes are complex. In general, energy barriers of up to ~5 kcal/mol were measured for removing the ligands from the minor groove, and of ~1.5 kcal/mol for sliding along the minor groove. We shed light on the way the minor groove geometry, defined mainly by the DNA sequence, shapes the binding landscape around DNA, providing heterogeneous environments for recognition by various ligands. For example, we identified the presence of dissociation points or "exit ramps" that naturally would terminate sliding. We discuss how our findings have important implications for understanding how proteins and ligands associate and slide along DNA.

  9. Effects of Supplemental Energy on Protein Balance during 4-d Arctic Military Training.

    Science.gov (United States)

    Margolis, Lee M; Murphy, Nancy E; Martini, Svein; Gundersen, Yngvar; Castellani, John W; Karl, J Philip; Carrigan, Christopher T; Teien, Hilde-Kristin; Madslien, Elisabeth-Henie; Montain, Scott J; Pasiakos, Stefan M

    2016-08-01

    Soldiers often experience negative energy balance during military operations that diminish whole-body protein retention, even when dietary protein is consumed within recommended levels (1.5-2.0 g·kg·d). The objective of this study is to determine whether providing supplemental nutrition spares whole-body protein by attenuating the level of negative energy balance induced by military training and to assess whether protein balance is differentially influenced by the macronutrient source. Soldiers participating in 4-d arctic military training (AMT) (51-km ski march) were randomized to receive three combat rations (CON) (n = 18), three combat rations plus four 250-kcal protein-based bars (PRO, 20 g protein) (n = 28), or three combat rations plus four 250-kcal carbohydrate-based bars daily (CHO, 48 g carbohydrate) (n = 27). Energy expenditure (D2O) and energy intake were measured daily. Nitrogen balance (NBAL) and protein turnover were determined at baseline (BL) and day 3 of AMT using 24-h urine and [N]-glycine. Protein and carbohydrate intakes were highest (P balance (-3313 ± 776 kcal·d), net protein balance (NET) (-0.24 ± 0.60 g·d), and NBAL (-68.5 ± 94.6 mg·kg·d) during AMT were similar between groups. In the combined cohort, energy intake was associated (P balance and NBAL during AMT. These data reinforce the importance of consuming sufficient energy during periods of high energy expenditure to mitigate the consequences of negative energy balance and attenuate whole-body protein loss.

  10. Landscape moderation of biodiversity patterns and processes - eight hypotheses.

    Science.gov (United States)

    Tscharntke, Teja; Tylianakis, Jason M; Rand, Tatyana A; Didham, Raphael K; Fahrig, Lenore; Batáry, Péter; Bengtsson, Janne; Clough, Yann; Crist, Thomas O; Dormann, Carsten F; Ewers, Robert M; Fründ, Jochen; Holt, Robert D; Holzschuh, Andrea; Klein, Alexandra M; Kleijn, David; Kremen, Claire; Landis, Doug A; Laurance, William; Lindenmayer, David; Scherber, Christoph; Sodhi, Navjot; Steffan-Dewenter, Ingolf; Thies, Carsten; van der Putten, Wim H; Westphal, Catrin

    2012-08-01

    Understanding how landscape characteristics affect biodiversity patterns and ecological processes at local and landscape scales is critical for mitigating effects of global environmental change. In this review, we use knowledge gained from human-modified landscapes to suggest eight hypotheses, which we hope will encourage more systematic research on the role of landscape composition and configuration in determining the structure of ecological communities, ecosystem functioning and services. We organize the eight hypotheses under four overarching themes. Section A: 'landscape moderation of biodiversity patterns' includes (1) the landscape species pool hypothesis-the size of the landscape-wide species pool moderates local (alpha) biodiversity, and (2) the dominance of beta diversity hypothesis-landscape-moderated dissimilarity of local communities determines landscape-wide biodiversity and overrides negative local effects of habitat fragmentation on biodiversity. Section B: 'landscape moderation of population dynamics' includes (3) the cross-habitat spillover hypothesis-landscape-moderated spillover of energy, resources and organisms across habitats, including between managed and natural ecosystems, influences landscape-wide community structure and associated processes and (4) the landscape-moderated concentration and dilution hypothesis-spatial and temporal changes in landscape composition can cause transient concentration or dilution of populations with functional consequences. Section C: 'landscape moderation of functional trait selection' includes (5) the landscape-moderated functional trait selection hypothesis-landscape moderation of species trait selection shapes the functional role and trajectory of community assembly, and (6) the landscape-moderated insurance hypothesis-landscape complexity provides spatial and temporal insurance, i.e. high resilience and stability of ecological processes in changing environments. Section D: 'landscape constraints on

  11. Jointly optimizing selection of fuel treatments and siting of forest biomass-based energy production facilities for landscape-scale fire hazard reduction.

    Science.gov (United States)

    Peter J. Daugherty; Jeremy S. Fried

    2007-01-01

    Landscape-scale fuel treatments for forest fire hazard reduction potentially produce large quantities of material suitable for biomass energy production. The analytic framework FIA BioSum addresses this situation by developing detailed data on forest conditions and production under alternative fuel treatment prescriptions, and computes haul costs to alternative sites...

  12. Sustainable City Regions: Re-localising Landscapes in a Globalising World

    Directory of Open Access Journals (Sweden)

    Robert Thayer Jnr

    2004-06-01

    Full Text Available This paper emphasises physical, technological and economic variables in a globalising world, and how they might influence local economies and local landscapes. With the expected 'big rollover' in demand versus supply of oil in the next decade, the scale of the landscape will change in response to a permanent rise in the price of transportation and shipping fuels. Air travel will become less accessible, as will shipping of high mass, low value-added materials and goods. This will necessitate the re-establishment of more local supplies and shorter transport distances for people and goods, and for the first time in human history the perceived size of the world will expand. In response, the 'grain' of the landscape will become finer. More people will populate the rural landscape, while cities and towns will become more compact. The landscape is influenced by the three major operative technological systems (matter, energy and information. While the depletion of oil will greatly affect matter and energy, it will have less influence on information, which is relatively immune from entropic thermodynamic effects. While source-to-end-use distances will shorten, world per-capita energy expenditures will fall, and more local goods will be created and consumed, it remains to be seen whether this contraction in the scale of the instrumental landscape will be matched by more localised ownership, or by continued globalisation of corporate systems of production and distribution. Assuming the former is preferable, the paper concludes by suggesting that the bioregion, or natural 'life place', is the appropriate location for the protection of biodiversity, sustained use of resources, and identity and life satisfaction of local inhabitants.

  13. supplementation of energy and/or protein to steers grazing summer ...

    African Journals Online (AJOL)

    Some aspects of the effect of supplementary energy and/or protein, strategically ptovided to steers on summer veld, were investi gated. 40 Friesland steers in the age ... was posed whether the strategic provision of energy and or protein to steers grazing .... Definitions and abbreviotions was determined after cooling for 24 h ...

  14. The greenGain project - Biomass from landscape conservation and maintenance work for renewable energy production in the EU

    Science.gov (United States)

    Clalüna, Aline; Baumgarten, Wibke; García Galindo, Daniel; Lenz, Klaus; Doležal, Jan; De Filippi, Federico; Lorenzo, Joaquín; Montagnoli, Louis

    2017-04-01

    The project greenGain is looking for solutions to increase the energy production with regional and local biomass from landscape conservation and maintenance work, which is performed in the public interest. The relevant resources analysed in the greenGain model regions are, among others, biomass residues from clearing invasive vegetation in marginal agricultural lands in Spain, and residues from abandoned vineyards and olive groves in landscape protected areas in Italy. The main target groups are regional and local players who are responsible for maintenance and conservation work and for the biomass residue management in their regions. Moreover, the focus will be on service providers - including farmers and forest owners, their associations, NGOs, energy providers and consumers. Local companies, municipalities and public authorities are collaborating to identify the still underutilised non-food biomass resources and to discuss the way to integrate them into the local and regional biomass markets. Since the start of the three year project in January 2015, the partners from Italy, Spain, Czech Republic and Germany analysed, among other, the biomass feedstock potential coming from landscape maintenance work, and assessed various technological options to utilise this type of biomass. Further, political, legal and environmental aspects as well as awareness raising and public acceptance actions regarding the energetic use of biomass from public areas were assessed. greenGain also facilitates the exchange between model regions and other similar relevant players in the EU and shares examples of good practice. General guidelines will be prepared to guarantee a wide dissemination to other regions in the EU. Thus, the project shows how to build-up reliable knowledge on local availability of this feedstock and provides know-how concerning planning, harvesting, pre-treatment, storage and sustainable conversion pathways to a wide range of stakeholders in the EU.

  15. Landscape Ecology

    DEFF Research Database (Denmark)

    Christensen, Andreas Aagaard; Brandt, Jesper; Svenningsen, Stig Roar

    2017-01-01

    Landscape ecology is an interdisciplinary field of research and practice that deals with the mutual association between the spatial configuration and ecological functioning of landscapes, exploring and describing processes involved in the differentiation of spaces within landscapes......, and the ecological significance of the patterns which are generated by such processes. In landscape ecology, perspectives drawn from existing academic disciplines are integrated based on a common, spatially explicit mode of analysis developed from classical holistic geography, emphasizing spatial and landscape...... pattern analysis and ecological interaction of land units. The landscape is seen as a holon: an assemblage of interrelated phenomena, both cultural and biophysical, that together form a complex whole. Enduring challenges to landscape ecology include the need to develop a systematic approach able...

  16. Landscape evolution space and the relative importance of geomorphic processes and controls

    Science.gov (United States)

    Phillips, Jonathan D.

    2009-08-01

    The concept of landscape evolution space (LES) is introduced as a tool for assessing landscapes and geomorphic systems, intended to be a systematic means for assessing the various factors that contribute to the potential for change in geomorphic systems. The LES conceptual model is based on the energy and mass available to drive and accommodate landscape evolution. An n-dimensional landscape evolution space is defined not only by spatial coordinates, but also by the availability of mass and energy. The LES is thus a space or hypervolume representing the resources available for geomorphic evolution and landscape change. An expression for LES is derived based on elevation, material density, surface area, and inputs of solar, meteoric, and biological energy and mass. Though primarily an heuristic device, the LES model can be used to address concrete problems. Two examples are given. In one, increased surface area due to topographic roughening and dissection of an incised plateau is found to only slightly offset erosional removals of mass in terms of the magnitude of the LES. In the other, sensitivity of coastal plain rivers to several impacts of sea level and climate change is explored. The LES model also leads to the concept of a geomorphological niche, representing the resources available to drive or support a specific process or suite of processes. Considerations of landscape evolution have traditionally focused on the interplay of endogenic vs. exogenic processes, uplift vs. denudation, or soil formation vs. erosion. The LES model explicitly broadens the conceptual framework of landscape evolution beyond the traditional dialectics.

  17. Free Energy Self-Averaging in Protein-Sized Random Heteropolymers

    International Nuclear Information System (INIS)

    Chuang, Jeffrey; Grosberg, Alexander Yu.; Kardar, Mehran

    2001-01-01

    Current theories of heteropolymers are inherently macroscopic, but are applied to mesoscopic proteins. To compute the free energy over sequences, one assumes self-averaging -- a property established only in the macroscopic limit. By enumerating the states and energies of compact 18, 27, and 36mers on a lattice with an ensemble of random sequences, we test the self-averaging approximation. We find that fluctuations in the free energy between sequences are weak, and that self-averaging is valid at the scale of real proteins. The results validate sequence design methods which exponentially speed up computational design and simplify experimental realizations

  18. European landscape architecture and territorial strategies for water landscapes

    DEFF Research Database (Denmark)

    Diedrich, Lisa Babette

    2010-01-01

    This article sums up the author’s lecture at the 2009 Sydney Resilient Water Landscapes Symposium and presents a series of realized or planned European landscape architectural and urbanistic projects on water landscapes taken from the recently published book On Site/ Landscape Architecture Europe...... and accompanying reflections. The hypothesis is that further scientific research can help defining weaknesses and strengths of the existing water landscape designs in terms of resilience, extract principles and tools, improve the weak ones and communicate the strong ones and develop general quality criteria...... and tools for future resilient water landscapes....

  19. Use of Bee Honey as Alternative Medicine in Protein Energy Deficiency

    OpenAIRE

    Prasetyo, R. Heru; Sandhika, Willy; Susanto, Djoni

    2013-01-01

    The protein energy deficiency cause intestinal villus atrophy and epithel mucous damage. The effect of bee honey on histostructure of intestine was studied in the experimental mice as model of proteinenergy deficiency. The use bee honey in protein-energy deficiency shown to improve intestinal villus atrophy and epithel damage. In conclusion that bee honey can use as alternative medicine in protein energydeficiency

  20. The effects of dietary energy and protein concentrations on ostrich ...

    African Journals Online (AJOL)

    The effects were investigated of energy and protein concentrations (with associated amino acid concentrations) in ostrich diets on leather quality of the skins of 50 ostriches. Energy concentrations were 9.0, 10.5 and 12.0 MJ ME/kg diet and protein concentrations were 130, 150 and 170 g/kg diet. The physical leather ...

  1. Microclimate landscape design at southern integrated terminal Bandar Tasik Selatan, Kuala Lumpur

    Science.gov (United States)

    Phin, L. H.; Krisantia, I.

    2018-01-01

    Bandar Tasik Selatan is the integrated transport terminal has high energy consuming, high carbon emission and poor linkage. However, microclimate can be reduced through landscape design. This paper is a study to achieve energy efficiency and improve microclimate in the urban area. The research area is at Southern integrated terminal Bandar Tasik Selatan Kuala Lumpur Malaysia. It is carried out through a case study and microclimate analyzed using System Modeling method. System modelling using in this research is system energy budget of the microclimate at a site is a balance between the radiant energy supplied and the energy removed by all consumers. The finding indicated the microclimatic components that can be modified through landscape design are solar radiation, wind and precipitation can create thermal comfort, energy efficiency and others benefits.Through this research, provide more green space to achieve energy efficiency and improve microclimate of the site, introducing vertical landscape and proper planting selection to improve air quality, introducing green energy as part of the source of power supply and to promote integration of terminal building and rail systems by unify them using softscape

  2. Leucine supplementation in the management of protein energy ...

    African Journals Online (AJOL)

    Objective: To establish if leucine could be used as a therapeutic agent in the treatment of protein energy malnutrition. Study selection: Based on defined key words a search was carried out on Pubmed to retrieve all publications on leucine supplementation and muscle protein synthesis. Only studies that met the search ...

  3. What determines the structures of native folds of proteins?

    International Nuclear Information System (INIS)

    Trovato, Antonio; Hoang, Trinh X; Banavar, Jayanth R; Maritan, Amos; Seno, Flavio

    2005-01-01

    We review a simple physical model (Hoang et al 2004 Proc. Natl Acad. Sci. USA 101 7960, Banavar et al 2004 Phys. Rev. E at press) which captures the essential physico-chemical ingredients that determine protein structure, such as the inherent anisotropy of a chain molecule, the geometrical and energetic constraints placed by hydrogen bonds, sterics, and hydrophobicity. Within this framework, marginally compact conformations resembling the native state folds of proteins emerge as competing minima in the free energy landscape. Here we demonstrate that a hydrophobic-polar (HP) sequence composed of regularly repeated patterns has as its ground state a β-helical structure remarkably similar to a known architecture in the Protein Data Bank

  4. Pharmacological chaperone reshapes the energy landscape for folding and aggregation of the prion protein

    Science.gov (United States)

    Gupta, Amar Nath; Neupane, Krishna; Rezajooei, Negar; Cortez, Leonardo M.; Sim, Valerie L.; Woodside, Michael T.

    2016-06-01

    The development of small-molecule pharmacological chaperones as therapeutics for protein misfolding diseases has proven challenging, partly because their mechanism of action remains unclear. Here we study Fe-TMPyP, a tetrapyrrole that binds to the prion protein PrP and inhibits misfolding, examining its effects on PrP folding at the single-molecule level with force spectroscopy. Single PrP molecules are unfolded with and without Fe-TMPyP present using optical tweezers. Ligand binding to the native structure increases the unfolding force significantly and alters the transition state for unfolding, making it more brittle and raising the barrier height. Fe-TMPyP also binds the unfolded state, delaying native refolding. Furthermore, Fe-TMPyP binding blocks the formation of a stable misfolded dimer by interfering with intermolecular interactions, acting in a similar manner to some molecular chaperones. The ligand thus promotes native folding by stabilizing the native state while also suppressing interactions driving aggregation.

  5. Energy and protein requirements for growth of the local domestic ...

    African Journals Online (AJOL)

    The diet 3 in the grower phase improved growth with the highest EFU, 0.12, and was better utilized by the birds than in the chick starter phase where it was least utilized. High energy, high protein diet enhanced growth while low energy, high protein diet did not support maximum growth especially in the chick starter phase.

  6. Ultra-fast evaluation of protein energies directly from sequence.

    Directory of Open Access Journals (Sweden)

    Gevorg Grigoryan

    2006-06-01

    Full Text Available The structure, function, stability, and many other properties of a protein in a fixed environment are fully specified by its sequence, but in a manner that is difficult to discern. We present a general approach for rapidly mapping sequences directly to their energies on a pre-specified rigid backbone, an important sub-problem in computational protein design and in some methods for protein structure prediction. The cluster expansion (CE method that we employ can, in principle, be extended to model any computable or measurable protein property directly as a function of sequence. Here we show how CE can be applied to the problem of computational protein design, and use it to derive excellent approximations of physical potentials. The approach provides several attractive advantages. First, following a one-time derivation of a CE expansion, the amount of time necessary to evaluate the energy of a sequence adopting a specified backbone conformation is reduced by a factor of 10(7 compared to standard full-atom methods for the same task. Second, the agreement between two full-atom methods that we tested and their CE sequence-based expressions is very high (root mean square deviation 1.1-4.7 kcal/mol, R2 = 0.7-1.0. Third, the functional form of the CE energy expression is such that individual terms of the expansion have clear physical interpretations. We derived expressions for the energies of three classic protein design targets-a coiled coil, a zinc finger, and a WW domain-as functions of sequence, and examined the most significant terms. Single-residue and residue-pair interactions are sufficient to accurately capture the energetics of the dimeric coiled coil, whereas higher-order contributions are important for the two more globular folds. For the task of designing novel zinc-finger sequences, a CE-derived energy function provides significantly better solutions than a standard design protocol, in comparable computation time. Given these advantages

  7. [Supercomputer investigation of the protein-ligand system low-energy minima].

    Science.gov (United States)

    Oferkin, I V; Sulimov, A V; Katkova, E V; Kutov, D K; Grigoriev, F V; Kondakova, O A; Sulimov, V B

    2015-01-01

    The accuracy of the protein-ligand binding energy calculations and ligand positioning is strongly influenced by the choice of the docking target function. This work demonstrates the evaluation of the five different target functions used in docking: functions based on MMFF94 force field and functions based on PM7 quantum-chemical method accounting or without accounting the implicit solvent model (PCM, COSMO or SGB). For these purposes the ligand positions corresponding to the minima of the target function and the experimentally known ligand positions in the protein active site (crystal ligand positions) were compared. Each function was examined on the same test-set of 16 protein-ligand complexes. The new parallelized docking program FLM based on Monte Carlo search algorithm was developed to perform the comprehensive low-energy minima search and to calculate the protein-ligand binding energy. This study demonstrates that the docking target function based on the MMFF94 force field can be used to detect the crystal or near crystal positions of the ligand by the finding the low-energy local minima spectrum of the target function. The importance of solvent accounting in the docking process for the accurate ligand positioning is also shown. The accuracy of the ligand positioning as well as the correlation between the calculated and experimentally determined protein-ligand binding energies are improved when the MMFF94 force field is substituted by the new PM7 method with implicit solvent accounting.

  8. Molecular mechanics calculations of proteins. Comparison of different energy minimization strategies

    DEFF Research Database (Denmark)

    Christensen, I T; Jørgensen, Flemming Steen

    1997-01-01

    A general strategy for performing energy minimization of proteins using the SYBYL molecular modelling program has been developed. The influence of several variables including energy minimization procedure, solvation, dielectric function and dielectric constant have been investigated in order...... to develop a general method, which is capable of producing high quality protein structures. Avian pancreatic polypeptide (APP) and bovine pancreatic phospholipase A2 (BP PLA2) were selected for the calculations, because high quality X-ray structures exist and because all classes of secondary structure...... for this protein. Energy minimized structures of the trimeric PLA2 from Indian cobra (N.n.n. PLA2) were used for assessing the impact of protein-protein interactions. Based on the above mentioned criteria, it could be concluded that using the following conditions: Dielectric constant epsilon = 4 or 20; a distance...

  9. Is protein-energy intake adequate during dialysis treatment in hemodialysis patients ?

    Directory of Open Access Journals (Sweden)

    Trudeke (G I. Struijk-Wielinga

    2012-06-01

    Conclusion: Protein and energy intake of hemodialysis patients is lower than their daily needs. On non dialysis days intake is even lower than on dialysis days. The meals consumed during dialysis treatment contain enough energy but not enough protein to meet requirements.

  10. The significance of the amorphous potential energy landscape for dictating glassy dynamics and driving solid-state crystallisation

    DEFF Research Database (Denmark)

    Ruggiero, Michael T; Krynski, Marcin; Kissi, Eric Ofosu

    2017-01-01

    clear experimental and computational evidence in support of a theory that proposes that the shape and structure of the potential-energy surface (PES) is the fundamental factor underlying the glass-transition processes, regardless of the frequency that experimental methods probe. Whilst this has been....... Combined, these findings provide compelling evidence that the PES landscape, and the corresponding energy barriers, are the ultimate controlling feature behind the atomic and molecular dynamics of disordered solids, regardless of the frequency at which they occur....... proposed previously, we demonstrate, using ab initio molecular-dynamics (AIMD) simulations, that it is of critical importance to carefully consider the complete PES - both the intra-molecular and inter-molecular features - in order to fully understand the entire range of atomic-dynamical processes...

  11. Communication Maps: Exploring Energy Transport through Proteins and Water

    Czech Academy of Sciences Publication Activity Database

    Agbo, J. K.; Gnanasekaran, Ramachandran; Leitner, D. M.

    2014-01-01

    Roč. 54, 8/9 (2014), s. 1065-1073 ISSN 0021-2148 Institutional support: RVO:61388963 Keywords : energy transfer * heme proteins * hydrogen bonds * molecular modeling * protein models Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.221, year: 2014

  12. Expanded explorations into the optimization of an energy function for protein design

    Science.gov (United States)

    Huang, Yao-ming; Bystroff, Christopher

    2014-01-01

    Nature possesses a secret formula for the energy as a function of the structure of a protein. In protein design, approximations are made to both the structural representation of the molecule and to the form of the energy equation, such that the existence of a general energy function for proteins is by no means guaranteed. Here we present new insights towards the application of machine learning to the problem of finding a general energy function for protein design. Machine learning requires the definition of an objective function, which carries with it the implied definition of success in protein design. We explored four functions, consisting of two functional forms, each with two criteria for success. Optimization was carried out by a Monte Carlo search through the space of all variable parameters. Cross-validation of the optimized energy function against a test set gave significantly different results depending on the choice of objective function, pointing to relative correctness of the built-in assumptions. Novel energy cross-terms correct for the observed non-additivity of energy terms and an imbalance in the distribution of predicted amino acids. This paper expands on the work presented at ACM-BCB, Orlando FL , October 2012. PMID:24384706

  13. Monosodium glutamate delivered in a protein-rich soup improves subsequent energy compensation.

    Science.gov (United States)

    Masic, Una; Yeomans, Martin R

    2014-01-01

    Previous research suggests that monosodium glutamate (MSG) may have a biphasic effect on appetite, increasing appetite within a meal with its flavour-enhancing effect, but enhancing subsequent satiety due to its proposed role as a predictor of protein content. The present study explored this by assessing the impact of a 450 g soup preload differing in MSG concentration (1 % MSG added (MSG+) or no MSG (MSG-)) and nutrient content (low-energy control or high-energy carbohydrate or high-energy protein) on rated appetite and ad libitum intake of a test meal in thirty-five low-restraint male volunteers using a within-participant design. Protein-rich preloads significantly reduced intake at the test meal and resulted in more accurate energy compensation than did carbohydrate-rich preloads. This energy compensation was stronger in the MSG+ protein conditions when compared with MSG+ carbohydrate conditions. No clear differences in rated appetite were seen in MSG or the macronutrient conditions alone during preload ingestion or 45 min after intake. Overall, these findings indicate that MSG may act to further improve energy compensation when provided in a protein-rich context.

  14. Directed Magnetic Particle Transport above Artificial Magnetic Domains Due to Dynamic Magnetic Potential Energy Landscape Transformation.

    Science.gov (United States)

    Holzinger, Dennis; Koch, Iris; Burgard, Stefan; Ehresmann, Arno

    2015-07-28

    An approach for a remotely controllable transport of magnetic micro- and/or nanoparticles above a topographically flat exchange-bias (EB) thin film system, magnetically patterned into parallel stripe domains, is presented where the particle manipulation is achieved by sub-mT external magnetic field pulses. Superparamagnetic core-shell particles are moved stepwise by the dynamic transformation of the particles' magnetic potential energy landscape due to the external magnetic field pulses without affecting the magnetic state of the thin film system. The magnetic particle velocity is adjustable in the range of 1-100 μm/s by the design of the substrate's magnetic field landscape (MFL), the particle-substrate distance, and the magnitude of the applied external magnetic field pulses. The agglomeration of magnetic particles is avoided by the intrinsic magnetostatic repulsion of particles due to the parallel alignment of the particles' magnetic moments perpendicular to the transport direction and parallel to the surface normal of the substrate during the particle motion. The transport mechanism is modeled by a quantitative theory based on the precise knowledge of the sample's MFL and the particle-substrate distance.

  15. Landscape services as boundary concept in landscape governance: Building social capital in collaboration and adapting the landscape

    NARCIS (Netherlands)

    Westerink, Judith; Opdam, Paul; Rooij, Van Sabine; Steingröver, Eveliene

    2017-01-01

    The landscape services concept provides a lens to study relations within the social-ecological networks that landscapes are, and to identify stakeholders as either providers or beneficiaries. However, landscape services can also be used as a boundary concept in collaborative landscape governance. We

  16. Critical Zone Services as a Measure for Evaluating the Trade-offs in Intensively Managed Landscapes

    Science.gov (United States)

    Richardson, M.; Kumar, P.

    2015-12-01

    The Critical Zone includes the range of biophysical processes occurring from the top of the vegetation canopy to the weathering zone below the groundwater table. These services (Field et al. 2015) provide a measure to value processes that support the goods and services from our landscapes. In intensively managed landscapes the provisioning and regulating services are being altered through anthropogenic energy inputs so as to derive more agricultural productivity from the landscapes. Land use change and other alterations to the environment result in positive and/or negative net Critical Zone services. Through studies in the Critical Zone Observatory for Intensively Managed Landscapes (IMLCZO), this research seeks to answer questions such as: Are perennial bioenergy crops or annual replaced crops better for the land and surrounding environment? How do we evaluate the products and services from the land for the energy and resources we put in? Before the economic valuation of Critical Zone services, these questions seemed abstract. However, with developments such as Critical Zone services and life cycle assessments, they are more concrete. To evaluate the trade-offs between positive and negative impacts, life cycle assessments are used to create an inventory of all the energy inputs and outputs in a landscape management system. Total energy is computed by summing the mechanical energy used to construct tile drains, fertilizer, and other processes involved in intensely managed landscapes and the chemical energy gained by the production of biofuels from bioenergy crops. A multi-layer canopy model (MLCan) computes soil, water, and nutrient outputs for each crop type, which can be translated into Critical Zone services. These values are then viewed alongside the energy inputs into the system to show the relationship between agricultural practices and their corresponding ecosystem and environmental impacts.

  17. Impacts of the cultivation of energy crops for generation of biogas on the landscape structure and avifauna; Auswirkungen des Energiepflanzenanbaus zur Biogaserzeugung auf Landschaftsstruktur und Avifauna

    Energy Technology Data Exchange (ETDEWEB)

    Ruehmkorf, Hilke

    2011-07-01

    In its effort to implement new climate and energy policies, Germany has been heavily promoting the adoption of renewable energies. This has brought about a dramatic change in the use of arable land during the last years. The primary objective of this study was therefore to assess the effect of energy cropping on existing landscape structures in intensively cultivated regions in the course of the year. According to the available structural parameters an investigation was conducted to ascertain the fallout of energy plant cultivation on both migratory and overwintering birds. The period covered entailed the winter months. Both the advent of the energy crops as well as the associated biogas facilities that sprang up outside built-in areas seem to have reshaped the existing agricultural landscape. Hence, an additional aim of this study was to identify birds that use biogas plants for breeding or as a feeding habitat in winter. In conclusion, it can be asserted that energy crops can definitely contribute to the expansion of structural diversity in the agricultural landscape provided those energy crops were not cultivated on a large scale prior to the advent of the biogas facilities. Hence, there is still room for further energy crop diversification as its potential has not been exhausted. During the winter months mostly common species such as the carrion crow or the wood pigeon consider the maize fields as a viable source of nutrition. Cranes are seen as newcomers, as they probably started resting in the 'Boerde' precisely due to the advent of energy maize cultivation. And more availability of nourishment when the ground is covered by snow is another benefit the avifauna reaps from biogas plants. However, for endangered farmland birds this type of nutrition is a rarely used source, as it runs counter to their escape strategies and food preferences. For these species the habitat function and the food availability depends especially on how the land is managed (e

  18. Landscape and Energy%景观和能源

    Institute of Scientific and Technical Information of China (English)

    德克·西蒙斯; 李佳怿(译); 吴晓彤(校)

    2016-01-01

    research-through-design projects. The Rotterdam case is produced with local stakeholders for the 2014 ‘Landscape and Energy’ book publication. This land-oriented case is complemented by a project on the seascape of the North Sea as a future energy landscape in the IABR-2016 project 2050: An Energetic Odyssey. Especialy the last case not only justifies the conclusion that landscape architecture can play a role but also that research-by-design is a strong instrument to help in policy making.

  19. A landscape ecology approach to assessing development impacts in the tropics: A geothermal energy example in Hawaii

    Science.gov (United States)

    Griffith, J.A.; Trettin, C.C.; O'Neill, R. V.

    2002-01-01

    Geographic information systems (GIS) are increasingly being used in environmental impact assessments (EIA) because GIS is useful for analysing spatial impacts of various development scenarios. Spatially representing these impacts provides another tool for landscape ecology in environmental and geographical investigations by facilitating analysis of the effects of landscape patterns on ecological processes and examining change over time. Landscape ecological principles are applied in this study to a hypothetical geothermal development project on the Island of Hawaii. Some common landscape pattern metrics were used to analyse dispersed versus condensed development scenarios and their effect on landscape pattern. Indices of fragmentation and patch shape did not appreciably change with additional development. The amount of forest to open edge, however, greatly increased with the dispersed development scenario. In addition, landscape metrics showed that a human disturbance had a greater simplifying effect on patch shape and also increased fragmentation than a natural disturbance. The use of these landscape pattern metrics can advance the methodology of applying GIS to EIA.

  20. Albumin synthesis in protein energy malnutrition

    Energy Technology Data Exchange (ETDEWEB)

    Duggan, C; Hardy, S; Kleinman, R E [Harvard Medical School, Boston, MA (United States); Lembcke, J [Instituto de Investigacion Nutricional, La Molina, Lima (Peru); Young, V E [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Lab. of Human Nutrition

    1994-12-31

    The dietary treatment of protein-energy malnutrition (PEM) has been designed on an empirical basis, with outcomes for successful management including body weight gain and resolution of apathy. We propose using the measurements of protein synthesis as a more objective measure of renourishment. We will therefore randomize a group of malnourished children (weigh-for-height Z score <-2.0) to receive either a standard (10% of calories as protein) or increased (15%) amount of dietary protein early in their recovery phase. We will calculate albumin synthesis rates via the flooding dose technique, using {sup 13}C-leucine and serial measurements of {sup 13}C-enrichment of albumin. Isotope infusions will be performed on days one and three, following a standard three hour fast. Since albumin synthesis is reduced under the influence of cytokines which mediate the inflammatory response, results will be stratified according to the presence or absence of clinically apparent infections. We hypothesize that the provision of added dietary protein will optimize albumin synthesis rates in PEM as well as attenuate the reduction in albumin synthesis seen in the presence of infections. (author). 20 refs.

  1. Strategies for the exploration of free energy landscapes: Unity in diversity and challenges ahead

    Directory of Open Access Journals (Sweden)

    Fabio Pietrucci

    2017-11-01

    Full Text Available Computer simulations play an important role in the study of transformation processes of condensed matter, including phase transitions, chemical reactions, and conformational changes of biomolecules. In principle, atomic trajectories, such as those generated using the molecular dynamics approach, contain detailed structural, thermodynamic, and kinetic information about activated processes. In practice, due to free energy barriers, there is often a wide gap between the time scale of the transformation and the time scale accessible with simulations. This review offers a practical guide to the ingenious methods aimed to accelerate the exploration and reconstruction of free energy landscapes of complex systems. The focus is on basic unifying concepts, successful strategies, and pitfalls, illustrated with examples of application to scientific problems from different disciplines. The current challenges in the field consist mainly in the cumbersome identification of optimal reaction coordinates and in the extensive recourse to expert human supervision and fine tuning of the algorithms. The full achievement of wide-spectrum formulations and easy reproducibility of results would constitute the breakthrough necessary to enter the era of routine use of enhanced sampling simulations.

  2. Hybrid organic–inorganic inks flatten the energy landscape in colloidal quantum dot solids

    KAUST Repository

    Liu, Mengxia

    2016-11-14

    Bandtail states in disordered semiconductor materials result in losses in open-circuit voltage (Voc) and inhibit carrier transport in photovoltaics. For colloidal quantum dot (CQD) films that promise low-cost, large-area, air-stable photovoltaics, bandtails are determined by CQD synthetic polydispersity and inhomogeneous aggregation during the ligand-exchange process. Here we introduce a new method for the synthesis of solution-phase ligand-exchanged CQD inks that enable a flat energy landscape and an advantageously high packing density. In the solid state, these materials exhibit a sharper bandtail and reduced energy funnelling compared with the previous best CQD thin films for photovoltaics. Consequently, we demonstrate solar cells with higher Voc and more efficient charge injection into the electron acceptor, allowing the use of a closer-to-optimum bandgap to absorb more light. These enable the fabrication of CQD solar cells made via a solution-phase ligand exchange, with a certified power conversion efficiency of 11.28%. The devices are stable when stored in air, unencapsulated, for over 1,000 h.

  3. Hybrid organic–inorganic inks flatten the energy landscape in colloidal quantum dot solids

    KAUST Repository

    Liu, Mengxia; Voznyy, Oleksandr; Sabatini, Randy; Arquer, F.  Pelayo Garcí a de; Munir, Rahim; Balawi, Ahmed  Hesham; Lan, Xinzheng; Fan, Fengjia; Walters, Grant; Kirmani, Ahmad R.; Hoogland, Sjoerd; Laquai, Fré dé ric; Amassian, Aram; Sargent, Edward  H.

    2016-01-01

    Bandtail states in disordered semiconductor materials result in losses in open-circuit voltage (Voc) and inhibit carrier transport in photovoltaics. For colloidal quantum dot (CQD) films that promise low-cost, large-area, air-stable photovoltaics, bandtails are determined by CQD synthetic polydispersity and inhomogeneous aggregation during the ligand-exchange process. Here we introduce a new method for the synthesis of solution-phase ligand-exchanged CQD inks that enable a flat energy landscape and an advantageously high packing density. In the solid state, these materials exhibit a sharper bandtail and reduced energy funnelling compared with the previous best CQD thin films for photovoltaics. Consequently, we demonstrate solar cells with higher Voc and more efficient charge injection into the electron acceptor, allowing the use of a closer-to-optimum bandgap to absorb more light. These enable the fabrication of CQD solar cells made via a solution-phase ligand exchange, with a certified power conversion efficiency of 11.28%. The devices are stable when stored in air, unencapsulated, for over 1,000 h.

  4. Protein electron transfer: is biology (thermo)dynamic?

    International Nuclear Information System (INIS)

    Matyushov, Dmitry V

    2015-01-01

    Simple physical mechanisms are behind the flow of energy in all forms of life. Energy comes to living systems through electrons occupying high-energy states, either from food (respiratory chains) or from light (photosynthesis). This energy is transformed into the cross-membrane proton-motive force that eventually drives all biochemistry of the cell. Life’s ability to transfer electrons over large distances with nearly zero loss of free energy is puzzling and has not been accomplished in synthetic systems. The focus of this review is on how this energetic efficiency is realized. General physical mechanisms and interactions that allow proteins to fold into compact water-soluble structures are also responsible for a rugged landscape of energy states and a broad distribution of relaxation times. Specific to a protein as a fluctuating thermal bath is the protein-water interface, which is heterogeneous both dynamically and structurally. The spectrum of interfacial fluctuations is a consequence of protein’s elastic flexibility combined with a high density of surface charges polarizing water dipoles into surface nanodomains. Electrostatics is critical to the protein function and the relevant questions are: (i) What is the spectrum of interfacial electrostatic fluctuations? (ii) Does the interfacial biological water produce electrostatic signatures specific to proteins? (iii) How is protein-mediated chemistry affected by electrostatics? These questions connect the fluctuation spectrum to the dynamical control of chemical reactivity, i.e. the dependence of the activation free energy of the reaction on the dynamics of the bath. Ergodicity is often broken in protein-driven reactions and thermodynamic free energies become irrelevant. Continuous ergodicity breaking in a dense spectrum of relaxation times requires using dynamically restricted ensembles to calculate statistical averages. When applied to the calculation of the rates, this formalism leads to the nonergodic

  5. Protein, energy and phosphorus supplementation of cattle fed low ...

    African Journals Online (AJOL)

    The effect of protein, energy and phosphorus supplements, fed ..... The results of this experiment confirm the basic concepts that ... article. The lack of response or even negative reaction to energy supplements under these conditions can be ...

  6. Free Energy Landscape of the Dissolution of Gibbsite at High pH

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Zhizhang; Kerisit, Sebastien N.; Stack, Andrew G.; Rosso, Kevin M.

    2018-03-26

    The individual elementary reactions involved in the dissolution of a solid into solution remain mostly speculative due to a lack of suitable, direct experimental probes. In this regard, we have applied atomistic simulations to map the free energy landscape of the dissolution of gibbsite from a step edge, as a model of metal hydroxide dissolution. The overall reaction combines kink site formation and kink site propagation. Two individual reactions were found to be rate-limiting for kink site formation, that is, the displacement of Al from a step site to a ledge adatom site and its detachment from ledge/terrace adatom sites into the solution. As a result, a pool of mobile and labile Al adsorbed species, or adatoms, exists before the release of Al into solution. Because of the quasi-hexagonal symmetry of gibbsite, kink site propagation can occur in multiple directions. Overall, the simulation results will enable the development of microscopic mechanistic models of metal oxide dissolution.

  7. Geomorpho-Landscapes

    Science.gov (United States)

    Farabollini, Piero; Lugeri, Francesca; Amadio, Vittorio

    2014-05-01

    Landscape is the object of human perceptions, being the image of spatial organization of elements and structures: mankind lives the first approach with the environment, viewing and feeling the landscape. Many definitions of landscape have been given over time: in this case we refer to the Landscape defined as the result of interaction among physical, biotic and anthropic phenomena acting in a different spatial-temporal scale (Foreman & Godron) Following an Aristotelic approach in studying nature, we can assert that " Shape is synthesis": so it is possible to read the land features as the expression of the endogenous and exogenous processes that mould earth surfaces; moreover, Landscape is the result of the interaction of natural and cultural components, and conditions the spatial-temporal development of a region. The study of the Landscape offers results useful in order to promote sustainable development, ecotourism, enhancement of natural and cultural heritage, popularization of the scientific knowledge. In Italy, a very important GIS-based tool to represent the territory is the "Carta della Natura" ("Map of Nature", presently coordinated by the ISPRA) that aims at assessing the state of the whole Italian territory, analyzing Landscape. The methodology follows a holistic approach, taking into consideration all the components of a landscape and then integrating the information. Each individual landscape, studied at different scales, shows distinctive elements: structural, which depend on physical form and specific spatial organization; functional, which depend on relationships created between biotic and abiotic elements, and dynamic, which depend on the successive evolution of the structure. The identification of the landscape units, recognized at different scales of analysis, allows an evaluation of the state of the land, referring to the dual risk/resource which characterizes the Italian country. An interesting opportunity is to discover those areas of unusual

  8. Experimental parameterization of an energy function for the simulation of unfolded proteins

    DEFF Research Database (Denmark)

    Norgaard, A.B.; Ferkinghoff-Borg, Jesper; Lindorff-Larsen, K.

    2008-01-01

    The determination of conformational preferences in unfolded and disordered proteins is an important challenge in structural biology. We here describe an algorithm to optimize energy functions for the simulation of unfolded proteins. The procedure is based on the maximum likelihood principle and e...... and can be applied to a range of experimental data and energy functions including the force fields used in molecular dynamics simulations.......The determination of conformational preferences in unfolded and disordered proteins is an important challenge in structural biology. We here describe an algorithm to optimize energy functions for the simulation of unfolded proteins. The procedure is based on the maximum likelihood principle...

  9. Landscape impact assessment for wind turbine development in Dyfed

    International Nuclear Information System (INIS)

    Blandford, C.; White, S.; Thomas, B.; Osment, F.

    1994-01-01

    The study aims to identify those areas in Dyfed where, in terms of landscape impact, local authorities might seek to exclude or encourage wind turbine development, provide guidelines which will assist local authorities in judging the impact of wind turbine developments on the landscape and provide a basis and framework for the preparation of planning policy guidelines for acceptable wind turbine and wind farm developments in Dyfed. The study context reviews current Government energy and planning policies for the encouragement of wind turbine developments. Dyfed County Council's relevant Structure Plan policies are also considered, as are the new draft policies relating directly to wind energy released by other authorities. The sizes and status of planning applications are summarised and the landscape implications and precedent set by the test case at Mynydd-y-Cemais is discussed. Public perception of wind power is reviewed in the context of research in Europe and the USA. (author)

  10. Biomass yield from an urban landscape

    Science.gov (United States)

    Utilizing biomass from urban landscapes could significantly contribute to the nation’s renewable energy needs. In 2007, an experiment was begun to evaluate the biomass production from a bermudagrass, Cynodon dactylon var. dactylon (L.) Pers., lawn in Woodward, Oklahoma and to estimate the potential...

  11. Free energy landscape of dissociative adsorption of methane on ideal and defected graphene from ab initio simulations

    Science.gov (United States)

    Wlazło, M.; Majewski, J. A.

    2018-03-01

    We study the dissociative adsorption of methane at the surface of graphene. Free energy profiles, which include activation energies for different steps of the reaction, are computed from constrained ab initio molecular dynamics. At 300 K, the reaction barriers are much lower than experimental bond dissociation energies of gaseous methane, strongly indicating that the graphene surface acts as a catalyst of methane decomposition. On the other hand, the barriers are still much higher than on the nickel surface. Methane dissociation therefore occurs at a higher rate on nickel than on graphene. This reaction is a prerequisite for graphene growth from a precursor gas. Thus, the growth of the first monolayer should be a fast and efficient process while subsequent layers grow at a diminished rate and in a more controllable manner. Defects may also influence reaction energetics. This is evident from our results, in which simple defects (Stone-Wales defect and nitrogen substitution) lead to different free energy landscapes at both dissociation and adsorption steps of the process.

  12. Association between uncoupling protein 2, adiponectin and resting energy expenditure in obese women with normal and low resting energy expenditure.

    Science.gov (United States)

    Taghadomi Masoumi, Zahra; Eshraghian, Mohammad Reza; Hedayati, Mahdi; Pishva, Hamideh

    2018-02-01

    Obesity is recognized as the most prevalent metabolic disease worldwide. Decreases in energy expenditure may increase risk of obesity. One of the key regulators of energy balance is uncoupling protein2 (UCP2), a transporter protein presents in mitochondrial inner membrane. Moreover, adiponectin is the most abundant adipocytokine, it may play a role in energy metabolism and gene expression of UCP2. The aim of this study was to investigate potential associations between the level of uncoupling protein 2 and adiponectin and their relationship with REE (Resting Energy Expenditure) in obese women with normal and low resting energy expenditure. A total of 49 subjects (women, 25-50 years old), were included in current study, 16 subjects with BMI > 30 and low resting energy expenditure, 17 subjects with BMI > 30 and normal resting energy expenditure and 16 non-obese subjects as a control group. Anthropometric, body composition parameters and resting energy expenditure were measured. Plasma adiponectin, UCP2 protein and total protein in PBMC were determined. Measured resting energy expenditure in obese subjects with low REE was significantly lower than other groups. Plasma adiponectin in the obese subjects with low REE was significantly lower compared to normal weight group. There was a significant relationship between 'UCP2 protein/Total protein' ratio and plasma adiponectin in obese group with low REE and in three groups when we pooled. There was a significant association between REE and plasma adiponectin in three groups when we pooled. There was a significant association between plasma adiponectin and REE. Moreover, there was a significant relationship between UCP2 and REE.

  13. Do geographically isolated wetlands influence landscape functions?

    Science.gov (United States)

    Cohen, Matthew J.; Creed, Irena F.; Alexander, Laurie C.; Basu, Nandita; Calhoun, Aram J.K.; Craft, Christopher; D’Amico, Ellen; DeKeyser, Edward S.; Fowler, Laurie; Golden, Heather E.; Jawitz, James W.; Kalla, Peter; Kirkman, L. Katherine; Lane, Charles R.; Lang, Megan; Leibowitz, Scott G.; Lewis, David Bruce; Marton, John; McLaughlin, Daniel L.; Mushet, David M.; Raanan-Kiperwas, Hadas; Rains, Mark C.; Smith, Lora; Walls, Susan C.

    2015-01-01

    Geographically isolated wetlands (GIWs), those surrounded by uplands, exchange materials, energy, and organisms with other elements in hydrological and habitat networks, contributing to landscape functions, such as flow generation, nutrient and sediment retention, and biodiversity support. GIWs constitute most of the wetlands in many North American landscapes, provide a disproportionately large fraction of wetland edges where many functions are enhanced, and form complexes with other water bodies to create spatial and temporal heterogeneity in the timing, flow paths, and magnitude of network connectivity. These attributes signal a critical role for GIWs in sustaining a portfolio of landscape functions, but legal protections remain weak despite preferential loss from many landscapes. GIWs lack persistent surface water connections, but this condition does not imply the absence of hydrological, biogeochemical, and biological exchanges with nearby and downstream waters. Although hydrological and biogeochemical connectivity is often episodic or slow (e.g., via groundwater), hydrologic continuity and limited evaporative solute enrichment suggest both flow generation and solute and sediment retention. Similarly, whereas biological connectivity usually requires overland dispersal, numerous organisms, including many rare or threatened species, use both GIWs and downstream waters at different times or life stages, suggesting that GIWs are critical elements of landscape habitat mosaics. Indeed, weaker hydrologic connectivity with downstream waters and constrained biological connectivity with other landscape elements are precisely what enhances some GIW functions and enables others. Based on analysis of wetland geography and synthesis of wetland functions, we argue that sustaining landscape functions requires conserving the entire continuum of wetland connectivity, including GIWs.

  14. Mixing Energy Models in Genetic Algorithms for On-Lattice Protein Structure Prediction

    Directory of Open Access Journals (Sweden)

    Mahmood A. Rashid

    2013-01-01

    Full Text Available Protein structure prediction (PSP is computationally a very challenging problem. The challenge largely comes from the fact that the energy function that needs to be minimised in order to obtain the native structure of a given protein is not clearly known. A high resolution 20×20 energy model could better capture the behaviour of the actual energy function than a low resolution energy model such as hydrophobic polar. However, the fine grained details of the high resolution interaction energy matrix are often not very informative for guiding the search. In contrast, a low resolution energy model could effectively bias the search towards certain promising directions. In this paper, we develop a genetic algorithm that mainly uses a high resolution energy model for protein structure evaluation but uses a low resolution HP energy model in focussing the search towards exploring structures that have hydrophobic cores. We experimentally show that this mixing of energy models leads to significant lower energy structures compared to the state-of-the-art results.

  15. Identifying Greater Sage-Grouse source and sink habitats for conservation planning in an energy development landscape.

    Science.gov (United States)

    Kirol, Christopher P; Beck, Jeffrey L; Huzurbazar, Snehalata V; Holloran, Matthew J; Miller, Scott N

    2015-06-01

    Conserving a declining species that is facing many threats, including overlap of its habitats with energy extraction activities, depends upon identifying and prioritizing the value of the habitats that remain. In addition, habitat quality is often compromised when source habitats are lost or fragmented due to anthropogenic development. Our objective was to build an ecological model to classify and map habitat quality in terms of source or sink dynamics for Greater Sage-Grouse (Centrocercus urophasianus) in the Atlantic Rim Project Area (ARPA), a developing coalbed natural gas field in south-central Wyoming, USA. We used occurrence and survival modeling to evaluate relationships between environmental and anthropogenic variables at multiple spatial scales and for all female summer life stages, including nesting, brood-rearing, and non-brooding females. For each life stage, we created resource selection functions (RSFs). We weighted the RSFs and combined them to form a female summer occurrence map. We modeled survival also as a function of spatial variables for nest, brood, and adult female summer survival. Our survival-models were mapped as survival probability functions individually and then combined with fixed vital rates in a fitness metric model that, when mapped, predicted habitat productivity (productivity map). Our results demonstrate a suite of environmental and anthropogenic variables at multiple scales that were predictive of occurrence and survival. We created a source-sink map by overlaying our female summer occurrence map and productivity map to predict habitats contributing to population surpluses (source habitats) or deficits (sink habitat) and low-occurrence habitats on the landscape. The source-sink map predicted that of the Sage-Grouse habitat within the ARPA, 30% was primary source, 29% was secondary source, 4% was primary sink, 6% was secondary sink, and 31% was low occurrence. Our results provide evidence that energy development and avoidance of

  16. Perceptron learning of pairwise contact energies for proteins incorporating the amino acid environment

    Science.gov (United States)

    Heo, Muyoung; Kim, Suhkmann; Moon, Eun-Joung; Cheon, Mookyung; Chung, Kwanghoon; Chang, Iksoo

    2005-07-01

    Although a coarse-grained description of proteins is a simple and convenient way to attack the protein folding problem, the construction of a global pairwise energy function which can simultaneously recognize the native folds of many proteins has resulted in partial success. We have sought the possibility of a systematic improvement of this pairwise-contact energy function as we extended the parameter space of amino acids, incorporating local environments of amino acids, beyond a 20×20 matrix. We have studied the pairwise contact energy functions of 20×20 , 60×60 , and 180×180 matrices depending on the extent of parameter space, and compared their effect on the learnability of energy parameters in the context of a gapless threading, bearing in mind that a 20×20 pairwise contact matrix has been shown to be too simple to recognize the native folds of many proteins. In this paper, we show that the construction of a global pairwise energy function was achieved using 1006 training proteins of a homology of less than 30%, which include all representatives of different protein classes. After parametrizing the local environments of the amino acids into nine categories depending on three secondary structures and three kinds of hydrophobicity (desolvation), the 16290 pairwise contact energies (scores) of the amino acids could be determined by perceptron learning and protein threading. These could simultaneously recognize all the native folds of the 1006 training proteins. When these energy parameters were tested on the 382 test proteins of a homology of less than 90%, 370 (96.9%) proteins could recognize their native folds. We set up a simple thermodynamic framework in the conformational space of decoys to calculate the unfolded fraction and the specific heat of real proteins. The different thermodynamic stabilities of E.coli ribonuclease H (RNase H) and its mutants were well described in our calculation, agreeing with the experiment.

  17. The multi-state energy landscape of the SAM-I riboswitch: A single-molecule Förster resonance energy transfer spectroscopy study

    Science.gov (United States)

    Manz, Christoph; Kobitski, Andrei Yu.; Samanta, Ayan; Jäschke, Andres; Nienhaus, G. Ulrich

    2018-03-01

    RNA (ribonucleic acid) molecules are highly flexible biopolymers fluctuating at physiological temperatures among many different conformations that are represented by minima in a hierarchical conformational free energy landscape. Here we have employed single-molecule FRET (smFRET) to explore the energy landscape of the B. subtilis yitJ SAM-I riboswitch (RS). In this small RNA molecule, specific binding of an S-adenosyl-L-methionine (SAM) ligand in the aptamer domain regulates gene expression by inducing structural changes in another domain, the expression platform, causing transcription termination by the RNA polymerase. We have measured smFRET histograms over wide ranges of Mg2+ concentration for three RS variants that were specifically labeled with fluorescent dyes on different sites. In the analysis, different conformations are associated with discrete Gaussian model distributions, which are typically fairly broad on the FRET efficiency scale and thus can be extremely challenging to unravel due to their mutual overlap. Our earlier work on two SAM-I RS variants revealed four major conformations. By introducing a global fitting procedure which models both the Mg2+ concentration dependencies of the fractional populations and the average FRET efficiencies of the individual FRET distributions according to Mg2+ binding isotherms, we were able to consistently describe the histogram data of both variants at all studied Mg2+ concentrations. With the third FRET-labeled variant, however, we found significant deviations when applying the four-state model to the data. This can arise because the different FRET labeling of the new variant allows two states to be distinguished that were previously not separable due to overlap. Indeed, the resulting five-state model presented here consistently describes the smFRET histograms of all three variants as well as their variations with Mg2+ concentration. We also performed a triangulation of the donor position for two of the constructs

  18. Albumin synthesis in protein energy malnutrition

    International Nuclear Information System (INIS)

    Duggan, C.; Hardy, S.; Kleinman, R.E.; Lembcke, J.; Young, V.E.

    1994-01-01

    The dietary treatment of protein-energy malnutrition (PEM) has been designed on an empirical basis, with outcomes for successful management including body weight gain and resolution of apathy. We propose using the measurements of protein synthesis as a more objective measure of renourishment. We will therefore randomize a group of malnourished children (weigh-for-height Z score 13 C-leucine and serial measurements of 13 C-enrichment of albumin. Isotope infusions will be performed on days one and three, following a standard three hour fast. Since albumin synthesis is reduced under the influence of cytokines which mediate the inflammatory response, results will be stratified according to the presence or absence of clinically apparent infections. We hypothesize that the provision of added dietary protein will optimize albumin synthesis rates in PEM as well as attenuate the reduction in albumin synthesis seen in the presence of infections. (author). 20 refs

  19. Sequence-Based Analysis of Thermal Adaptation and Protein Energy Landscapes in an Invasive Blue Mussel (Mytilus galloprovincialis).

    Science.gov (United States)

    Saarman, Norah P; Kober, Kord M; Simison, W Brian; Pogson, Grant H

    2017-10-01

    Adaptive responses to thermal stress in poikilotherms plays an important role in determining competitive ability and species distributions. Amino acid substitutions that affect protein stability and modify the thermal optima of orthologous proteins may be particularly important in this context. Here, we examine a set of 2,770 protein-coding genes to determine if proteins in a highly invasive heat tolerant blue mussel (Mytilus galloprovincialis) contain signals of adaptive increases in protein stability relative to orthologs in a more cold tolerant M. trossulus. Such thermal adaptations might help to explain, mechanistically, the success with which the invasive marine mussel M. galloprovincialis has displaced native species in contact zones in the eastern (California) and western (Japan) Pacific. We tested for stabilizing amino acid substitutions in warm tolerant M. galloprovincialis relative to cold tolerant M. trossulus with a generalized linear model that compares in silico estimates of recent changes in protein stability among closely related congeners. Fixed substitutions in M. galloprovincialis were 3,180.0 calories per mol per substitution more stabilizing at genes with both elevated dN/dS ratios and transcriptional responses to heat stress, and 705.8 calories per mol per substitution more stabilizing across all 2,770 loci investigated. Amino acid substitutions concentrated in a small number of genes were more stabilizing in M. galloprovincialis compared with cold tolerant M. trossulus. We also tested for, but did not find, enrichment of a priori GO terms in genes with elevated dN/dS ratios in M. galloprovincialis. This might indicate that selection for thermodynamic stability is generic across all lineages, and suggests that the high change in estimated protein stability that we observed in M. galloprovincialis is driven by selection for extra stabilizing substitutions, rather than by higher incidence of selection in a greater number of genes in this lineage

  20. Thermal motion in proteins: Large effects on the time-averaged interaction energies

    International Nuclear Information System (INIS)

    Goethe, Martin; Rubi, J. Miguel; Fita, Ignacio

    2016-01-01

    As a consequence of thermal motion, inter-atomic distances in proteins fluctuate strongly around their average values, and hence, also interaction energies (i.e. the pair-potentials evaluated at the fluctuating distances) are not constant in time but exhibit pronounced fluctuations. These fluctuations cause that time-averaged interaction energies do generally not coincide with the energy values obtained by evaluating the pair-potentials at the average distances. More precisely, time-averaged interaction energies behave typically smoother in terms of the average distance than the corresponding pair-potentials. This averaging effect is referred to as the thermal smoothing effect. Here, we estimate the strength of the thermal smoothing effect on the Lennard-Jones pair-potential for globular proteins at ambient conditions using x-ray diffraction and simulation data of a representative set of proteins. For specific atom species, we find a significant smoothing effect where the time-averaged interaction energy of a single atom pair can differ by various tens of cal/mol from the Lennard-Jones potential at the average distance. Importantly, we observe a dependency of the effect on the local environment of the involved atoms. The effect is typically weaker for bulky backbone atoms in beta sheets than for side-chain atoms belonging to other secondary structure on the surface of the protein. The results of this work have important practical implications for protein software relying on free energy expressions. We show that the accuracy of free energy expressions can largely be increased by introducing environment specific Lennard-Jones parameters accounting for the fact that the typical thermal motion of protein atoms depends strongly on their local environment.

  1. HUBUNGAN KONSUMSI ENERGI, PROTEIN DENGAN AKTIVITAS KERJA PADA WANITA USIA SUBUR HIPERTIROID

    Directory of Open Access Journals (Sweden)

    Sri Supadmi

    2013-02-01

    Full Text Available Based on the results of urine iodine in the evaluation survey in 1998 and in 2003 had appeared hyperthyroidism cases this shows that some residents already on the status of iodine which can cause the symptoms of health problems in particular can cause a sense of fatigue as a result of increased energy demand will impact on the daily work activities, thus the quality of work activity to be low. These result aims to relationship of energy and protein consumption with work activity in women of childbearing age with hyperthyroidism. Design cross sectional study of two sample types of quantitative research. Research location in Magelang District. Sample in women of childbearing age who were taken by systematic sampling. Total samples were 100 people consisting of 50 persons hyperthyroidism and 50 persons eutiroid. Rank spearman analysis results for the relationship of energy consumption with work activities rho values obtained for 0,122. There is no significant difJeremce between energi consumption with work activity in women of 'childbearing age with hyperthyroidism. Rank Spearman analysis results for the relationship of protein consumtion with work activities rho values obtained for 0,165. There is no significant difJerence between protein consumption with work activity in women of childbearing age with hyperthyroidism. These results indicate a very weak relationship between protein consumption with work activities. There is a positive relationship between energy consumption with work activities, whicli mean that the higher the energy consumption the higher work activities. There is also a positive relationship between protein consumtion with work activities.Key words : energy, protein, work activities, hyperthyroidism

  2. Thermal motion in proteins: Large effects on the time-averaged interaction energies

    Energy Technology Data Exchange (ETDEWEB)

    Goethe, Martin, E-mail: martingoethe@ub.edu; Rubi, J. Miguel [Departament de Física Fonamental, Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona (Spain); Fita, Ignacio [Institut de Biologia Molecular de Barcelona, Baldiri Reixac 10, 08028 Barcelona (Spain)

    2016-03-15

    As a consequence of thermal motion, inter-atomic distances in proteins fluctuate strongly around their average values, and hence, also interaction energies (i.e. the pair-potentials evaluated at the fluctuating distances) are not constant in time but exhibit pronounced fluctuations. These fluctuations cause that time-averaged interaction energies do generally not coincide with the energy values obtained by evaluating the pair-potentials at the average distances. More precisely, time-averaged interaction energies behave typically smoother in terms of the average distance than the corresponding pair-potentials. This averaging effect is referred to as the thermal smoothing effect. Here, we estimate the strength of the thermal smoothing effect on the Lennard-Jones pair-potential for globular proteins at ambient conditions using x-ray diffraction and simulation data of a representative set of proteins. For specific atom species, we find a significant smoothing effect where the time-averaged interaction energy of a single atom pair can differ by various tens of cal/mol from the Lennard-Jones potential at the average distance. Importantly, we observe a dependency of the effect on the local environment of the involved atoms. The effect is typically weaker for bulky backbone atoms in beta sheets than for side-chain atoms belonging to other secondary structure on the surface of the protein. The results of this work have important practical implications for protein software relying on free energy expressions. We show that the accuracy of free energy expressions can largely be increased by introducing environment specific Lennard-Jones parameters accounting for the fact that the typical thermal motion of protein atoms depends strongly on their local environment.

  3. The renewable energies: the landscape

    International Nuclear Information System (INIS)

    Acket, C.; Bacher, P.

    2005-03-01

    If one takes into account the hydroelectric power, the France is the first european country in the renewable energies domain. The position is also honorable concerning the wood energy. Meanwhile, for the solar and wind energy, France is late. To discuss this debate, the authors bring together today data on the renewable energies, offer some proposals for the next 50 years taking into account the reduction of greenhouse gases emission for 2050. (A.L.B.)

  4. Low-temperature protein dynamics of the B800 molecules in the LH2 light-harvesting complex: spectral hole burning study and comparison with single photosynthetic complex spectroscopy.

    Science.gov (United States)

    Grozdanov, Daniel; Herascu, Nicoleta; Reinot, Tõnu; Jankowiak, Ryszard; Zazubovich, Valter

    2010-03-18

    Previously published and new spectral hole burning (SHB) data on the B800 band of LH2 light-harvesting antenna complex of Rps. acidophila are analyzed in light of recent single photosynthetic complex spectroscopy (SPCS) results (for a review, see Berlin et al. Phys. Life Rev. 2007, 4, 64.). It is demonstrated that, in general, SHB-related phenomena observed for the B800 band are in qualitative agreement with the SPCS data and the protein models involving multiwell multitier protein energy landscapes. Regarding the quantitative agreement, we argue that the single-molecule behavior associated with the fastest spectral diffusion (smallest barrier) tier of the protein energy landscape is inconsistent with the SHB data. The latter discrepancy can be attributed to SPCS probing not only the dynamics of of the protein complex per se, but also that of the surrounding amorphous host and/or of the host-protein interface. It is argued that SHB (once improved models are developed) should also be able to provide the average magnitudes and probability distributions of light-induced spectral shifts and could be used to determine whether SPCS probes a set of protein complexes that are both intact and statistically relevant. SHB results are consistent with the B800 --> B850 energy-transfer models including consideration of the whole B850 density of states.

  5. gRINN: a tool for calculation of residue interaction energies and protein energy network analysis of molecular dynamics simulations.

    Science.gov (United States)

    Serçinoglu, Onur; Ozbek, Pemra

    2018-05-25

    Atomistic molecular dynamics (MD) simulations generate a wealth of information related to the dynamics of proteins. If properly analyzed, this information can lead to new insights regarding protein function and assist wet-lab experiments. Aiming to identify interactions between individual amino acid residues and the role played by each in the context of MD simulations, we present a stand-alone software called gRINN (get Residue Interaction eNergies and Networks). gRINN features graphical user interfaces (GUIs) and a command-line interface for generating and analyzing pairwise residue interaction energies and energy correlations from protein MD simulation trajectories. gRINN utilizes the features of NAMD or GROMACS MD simulation packages and automatizes the steps necessary to extract residue-residue interaction energies from user-supplied simulation trajectories, greatly simplifying the analysis for the end-user. A GUI, including an embedded molecular viewer, is provided for visualization of interaction energy time-series, distributions, an interaction energy matrix, interaction energy correlations and a residue correlation matrix. gRINN additionally offers construction and analysis of Protein Energy Networks, providing residue-based metrics such as degrees, betweenness-centralities, closeness centralities as well as shortest path analysis. gRINN is free and open to all users without login requirement at http://grinn.readthedocs.io.

  6. Modeling disordered regions in proteins using Rosetta.

    Directory of Open Access Journals (Sweden)

    Ray Yu-Ruei Wang

    Full Text Available Protein structure prediction methods such as Rosetta search for the lowest energy conformation of the polypeptide chain. However, the experimentally observed native state is at a minimum of the free energy, rather than the energy. The neglect of the missing configurational entropy contribution to the free energy can be partially justified by the assumption that the entropies of alternative folded states, while very much less than unfolded states, are not too different from one another, and hence can be to a first approximation neglected when searching for the lowest free energy state. The shortcomings of current structure prediction methods may be due in part to the breakdown of this assumption. Particularly problematic are proteins with significant disordered regions which do not populate single low energy conformations even in the native state. We describe two approaches within the Rosetta structure modeling methodology for treating such regions. The first does not require advance knowledge of the regions likely to be disordered; instead these are identified by minimizing a simple free energy function used previously to model protein folding landscapes and transition states. In this model, residues can be either completely ordered or completely disordered; they are considered disordered if the gain in entropy outweighs the loss of favorable energetic interactions with the rest of the protein chain. The second approach requires identification in advance of the disordered regions either from sequence alone using for example the DISOPRED server or from experimental data such as NMR chemical shifts. During Rosetta structure prediction calculations the disordered regions make only unfavorable repulsive contributions to the total energy. We find that the second approach has greater practical utility and illustrate this with examples from de novo structure prediction, NMR structure calculation, and comparative modeling.

  7. Connecting Brabant's cover sand landscapes through landscape history

    Science.gov (United States)

    Heskes, Erik; van den Ancker, Hanneke; Jungerius, Pieter Dirk; Harthoorn, Jaap; Maes, Bert; Leenders, Karel; de Jongh, Piet; Kluiving, Sjoerd; van den Oetelaar, Ger

    2015-04-01

    Noord-Brabant has the largest variety of cover sand landscapes in The Netherlands, and probably in Western Europe. During the Last Ice Age the area was not covered by land ice and a polar desert developed in which sand dunes buried the existing river landscapes. Some of these polar dune landscapes experienced a geomorphological and soil development that remained virtually untouched up to the present day, such as the low parabolic dunes of the Strabrechtse Heide or the later and higher dunes of the Oisterwijkse Vennen. As Noord-Brabant lies on the fringe of a tectonic basin, the thickness of cover sand deposits in the Centrale Slenk, part of a rift through Europe, amounts up to 20 metres. Cover sand deposits along the fault lines cause the special phenomenon of 'wijst' to develop, in which the higher grounds are wetter than the boarding lower grounds. Since 4000 BC humans settled in these cover sand landscapes and made use of its small-scale variety. An example are the prehistoric finds on the flanks and the historic towns on top of the 'donken' in northwest Noord-Brabant, where the cover sand landscapes are buried by river and marine deposits and only the peaks of the dunes protrude as donken. Or the church of Handel that is built beside a 'wijst' source and a site of pilgrimage since living memory. Or the 'essen' and plaggen agriculture that developed along the stream valleys of Noord-Brabant from 1300 AD onwards, giving rise to geomorphological features as 'randwallen' and plaggen soils of more than a metre thickness. Each region of Brabant each has its own approach in attracting tourists and has not yet used this common landscape history to connect, manage and promote their territories. We propose a landscape-historical approach to develop a national or European Geopark Brabants' cover sand landscapes, in which each region focuses on a specific part of the landscape history of Brabant, that stretches from the Late Weichselian polar desert when the dune

  8. Mountains and energy transition. Status of use of renewable energies and challenges for their development in mountain areas - Renewable energies Volume 1

    International Nuclear Information System (INIS)

    Peguin, Marion; Moncorps, Sebastien; Fourcade, Michel; Denis, Helene

    2013-10-01

    After an overview of challenges related to the development of renewable energies in mountain areas (conservation of biodiversity and landscapes, main legal measures regarding biodiversity and landscapes), this report proposes an overview of the status and potentials of the different renewable energies (solar, wind, hydroelectricity, bio-energies, geothermal) in mountain areas. It proposes an assessment (strengths and weaknesses) and recommendations for solar, wind, hydroelectricity and bio energies in mountain areas

  9. Protein blend ingestion before allogeneic stem cell transplantation improves protein-energy malnutrition in patients with leukemia.

    Science.gov (United States)

    Ren, Guangxu; Zhang, Jianping; Li, Minghua; Yi, Suqin; Xie, Jin; Zhang, Hongru; Wang, Jing

    2017-10-01

    Severe protein-energy malnutrition (PEM) and skeletal muscle wasting are commonly observed in patients with acute leukemia. Recently, the ingestion of a soy-whey protein blend has been shown to promote muscle protein synthesis (MPS). Thus, we tested the hypothesis that the ingestion of a soy-whey blended protein (BP) may improve the PEM status and muscle mass in acute leukemia patients. In total, 24 patients from the same treatment group were randomly assigned to the natural diet plus soy-whey blended protein (BP) group and the natural diet only (ND) group. Our data showed that protein and energy intake decreased significantly (P protein) were observed in the majority (>50%) of the patients. However, 66% of the patients who ingested the BP before transplantation showed obvious increases in arm muscle area. The gripping power value (△ post-pre or △ post-baseline ) was significantly higher in the BP group than in the ND group (P protein to different extents. Notably, the average time to stem cell engraftment was significantly shorter for patients in the BP group (12.2 ± 2.0 days) than for patients in the ND group (15.1 ± 2.9 days). Collectively, our data supported that soy-whey protein can improve PEM status and muscle mass in leukemia patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Quantum localization and protein-assisted vibrational energy flow in cofactors

    International Nuclear Information System (INIS)

    Leitner, David M

    2010-01-01

    Quantum effects influence vibrational dynamics and energy flow in biomolecules, which play a central role in biomolecule function, including control of reaction kinetics. Lifetimes of many vibrational modes of proteins and their temperature dependence, as determined by quantum golden-rule-based calculations, exhibit trends consistent with experimental observation and distinct from estimates based on classical modeling. Particularly notable are quantum coherence effects that give rise to localization of vibrational states of sizable organic molecules in the gas phase. Even when such a molecule, for instance a cofactor, is embedded in a protein, remnants of quantum localization survive that influence vibrational energy flow and its dependence on temperature. We discuss these effects on the mode-damping rates of a cofactor embedded in a protein, using the green fluorescent protein chromophore as a specific example. We find that for cofactors of this size embedded in their protein and solvent environment at room temperature a golden-rule calculation often overestimates the mode-damping rate.

  11. PROTEIN AND/OR ENERGY SUPPLEMENTATION OF LACTATING ...

    African Journals Online (AJOL)

    intake of a lactating beef cow and the chemical composttion of'the grass sward, it was cstimated that the veld supplred 90 per ccnt.65 ... (iv) a low calcium and phosphate content of the veld ... cent for those on a high energy-low protein diet.

  12. Energy Saver: Tips on Saving Money & Energy at Home

    Energy Technology Data Exchange (ETDEWEB)

    None

    2017-09-01

    Provides consumers with home energy and money savings tips such as insulation, weatherization, heating, cooling, water heating, energy efficient windows, landscaping, lighting, and energy efficient appliances.

  13. Energy Savers: Tips on Saving Money & Energy at Home

    Energy Technology Data Exchange (ETDEWEB)

    None

    2011-12-01

    Provides consumers with home energy and money savings tips such as insulation, weatherization, heating, cooling, water heating, energy efficient windows, landscaping, lighting, and energy efficient appliances.

  14. Energy Savers: Tips on Saving Money & Energy at Home

    Energy Technology Data Exchange (ETDEWEB)

    None

    2014-05-01

    Provides consumers with home energy and money savings tips such as insulation, weatherization, heating, cooling, water heating, energy efficient windows, landscaping, lighting, and energy efficient appliances.

  15. Energy Savers Tips on Saving Energy& Money at Home

    Energy Technology Data Exchange (ETDEWEB)

    2003-06-01

    Provides consumers with home energy and money savings tips such as insulation, weatherization, heating, cooling, water heating, energy efficient windows, landscaping, lighting, and energy efficient appliances

  16. Towards an Integrated Energy Landscape

    NARCIS (Netherlands)

    de Boer, Jessica; Zuidema, Christian

    2013-01-01

    In this paper, we show that an area-based approach to fostering the ‘energy transition’ has potential to help spatial planners and policy makers understand how innovative sustainable energy initiatives may contribute to the energy transition. On the basis of a desk study of research reports on

  17. Machine learning for the structure-energy-property landscapes of molecular crystals.

    Science.gov (United States)

    Musil, Félix; De, Sandip; Yang, Jack; Campbell, Joshua E; Day, Graeme M; Ceriotti, Michele

    2018-02-07

    Molecular crystals play an important role in several fields of science and technology. They frequently crystallize in different polymorphs with substantially different physical properties. To help guide the synthesis of candidate materials, atomic-scale modelling can be used to enumerate the stable polymorphs and to predict their properties, as well as to propose heuristic rules to rationalize the correlations between crystal structure and materials properties. Here we show how a recently-developed machine-learning (ML) framework can be used to achieve inexpensive and accurate predictions of the stability and properties of polymorphs, and a data-driven classification that is less biased and more flexible than typical heuristic rules. We discuss, as examples, the lattice energy and property landscapes of pentacene and two azapentacene isomers that are of interest as organic semiconductor materials. We show that we can estimate force field or DFT lattice energies with sub-kJ mol -1 accuracy, using only a few hundred reference configurations, and reduce by a factor of ten the computational effort needed to predict charge mobility in the crystal structures. The automatic structural classification of the polymorphs reveals a more detailed picture of molecular packing than that provided by conventional heuristics, and helps disentangle the role of hydrogen bonded and π-stacking interactions in determining molecular self-assembly. This observation demonstrates that ML is not just a black-box scheme to interpolate between reference calculations, but can also be used as a tool to gain intuitive insights into structure-property relations in molecular crystal engineering.

  18. Strategic study on energy-protein requirements for local sheep: 5. Ewes during lactation phase

    Directory of Open Access Journals (Sweden)

    I-W Mathius

    2004-03-01

    Full Text Available Thirty-six Javanese thin-tail ewes in the end of late pregnancy phase were set out to study the energy and crude protein requirements during the first eight-week of lactation phase. The ewes were penned individually in doors and randomly assigned to a 3 x 3 factorial arrangement, consisting of three levels of energy (low, medium and high and three levels of crude protein (low, medium and high diets with four ewes per treatment. The diets were pelleted and offered four times daily in approximately equal amount. Feed intake, nutrient digestibility, body weight and milk production were recorded. Results showed that, total lamb birth weights was not affected, but protein content on the ration treatments significantly altered (P0.05, while crude protein content on the ration highly significantly affected (P<0.01. Based on data recorded, the energy and protein requirements for ewes during lactation phase are highly significantly depended on ewes’ live weight, milk production and the ratio of energy metabolism and crude protein of the ration. It was concluded that in order to fulfil the crude protein and energy needs of the ewes during lactation phase, the ration given should contain crude protein and energy as much as 16% (based on dry matter and 13.4 MJ/kg dry matter respectively.

  19. Analysis of the free-energy surface of proteins from reversible folding simulations.

    Directory of Open Access Journals (Sweden)

    Lucy R Allen

    2009-07-01

    Full Text Available Computer generated trajectories can, in principle, reveal the folding pathways of a protein at atomic resolution and possibly suggest general and simple rules for predicting the folded structure of a given sequence. While such reversible folding trajectories can only be determined ab initio using all-atom transferable force-fields for a few small proteins, they can be determined for a large number of proteins using coarse-grained and structure-based force-fields, in which a known folded structure is by construction the absolute energy and free-energy minimum. Here we use a model of the fast folding helical lambda-repressor protein to generate trajectories in which native and non-native states are in equilibrium and transitions are accurately sampled. Yet, representation of the free-energy surface, which underlies the thermodynamic and dynamic properties of the protein model, from such a trajectory remains a challenge. Projections over one or a small number of arbitrarily chosen progress variables often hide the most important features of such surfaces. The results unequivocally show that an unprojected representation of the free-energy surface provides important and unbiased information and allows a simple and meaningful description of many-dimensional, heterogeneous trajectories, providing new insight into the possible mechanisms of fast-folding proteins.

  20. Assessment of landscape diversity and determination of landscape hotspots - a case of Slovenia

    Science.gov (United States)

    Perko, Drago; Ciglič, Rok; Hrvatin, Mauro

    2017-04-01

    Areas with high landscape diversity can be regarded as landscape hotspots, and vice versa areas with low landscape diversity can be marked as landscape coldspots. The main purpose of this paper is to use quantitative geoinformatical approach and identify parts of our test area (the country of Slovenia) that can be described as very diverse according to natural landscapes and natural elements. We used different digital raster data of natural elements and landscape classifications and defined landscape diversity and landscape hotspots. We defined diversity for each raster pixel by counting the number of different unique types of landscape elements and types of landscapes in its neighborhood. Namely, the method was used separately to define diversity according to natural elements (types of relief forms, rocks, and vegetation) and diversity according to existing geographical landscape classifications of Slovenia (types of landscapes). In both cases one-tenth of Slovenia's surface with the highest landscape diversity was defined as landscape hotspots. The same applies to the coldspots. Additionally we tested the same method of counting different types of landscapes in certain radius also for the area of Europe in order to find areas that are more diverse at continental level. By doing so we were able to find areas that have similar level of diversity as Slovenia according to different European landscape classifications. Areas with landscape diversity may have an advantage in economic development, especially in tourism. Such areas are also important for biodiversity, habitat, and species diversity. On the other hand, localities where various natural influences mix can also be areas where it is hard to transfer best practices from one place to another because of the varying responses of the landscapes to human intervention. Thus it is important to know where areas with high landscape diversity are.

  1. Does reintroducing large wood influence the hydraulic landscape of a lowland river system?

    Science.gov (United States)

    Matheson, Adrian; Thoms, Martin; Reid, Michael

    2017-09-01

    Our understanding of the effectiveness of reintroduced large wood for restoration is largely based on studies from high energy river systems. By contrast, few studies of the effectiveness of reintroducing large wood have been undertaken on large, low energy, lowland river systems: river systems where large wood is a significant physical feature on the in-channel environment. This study investigated the effect of reintroduced large wood on the hydraulic landscape of the Barwon-Darling River, Australia, at low flows. To achieve this, the study compared three hydraulic landscapes of replicated reference (naturally wooded), control (unwooded,) and managed (wood reintroduced) treatments on three low flow periods. These time periods were prior to the reintroduction of large wood to managed reaches; several months after the reintroduction of large wood into the managed reaches; and then more than four years after wood reintroduction following several large flood events. Hydraulic landscapes of reaches were characterised using a range of spatial measures calculated from velocity measurements taken with a boat-mounted Acoustic Doppler Profiler. We hypothesised that reintroduced large wood would increase the diversity of the hydraulic landscape at low flows and that managed reaches would be more similar to the reference reaches. Our results suggest that the reintroduction of large wood did not significantly change the character of the hydraulic landscape at the reach scale after several months (p = 0.16) or several years (p = 0.29). Overall, the character of the hydraulic landscape in the managed reaches was more similar to the hydraulic landscape of the control reaches than the hydraulic landscape of the reference reaches, at low flows. Some variability in the hydraulic landscapes was detected over time, and this may reflect reworking of riverbed sediments and sensitivity to variation in discharge. The lack of a response in the low flow hydraulic landscape to the

  2. Conference on wind power development in the face of landscape and local project acceptability challenges

    International Nuclear Information System (INIS)

    Victoire Lejzerzon; Sauron, Claire; Villot, Marie; Ratzbor, Guenter; Tausch, Christian; Cagneaux, Bertrand; Jouneau, Agathe; Stemmer, Boris; Huebner, Gundula; Orozco-Souel, Paola; Lhermitte, Charles; Ferus, Elisabeth; Benezech, Philippe; Gunzelmann, Thomas

    2015-01-01

    The French-German office for Renewable energies (OFAEnR) organised a conference on n wind power development in the face of landscape and local project acceptability challenges. In the framework of this French-German exchange of experience, participants addressed the following points: the conciliation between landscape protection and wind power development, the definition of landscape environmental quality criteria, the needs and usages of the departments in charge of the treatment of landscape studies in France, the socio-psychological approach of the local acceptability of wind farm projects, the re-powering tool for the improvement of the wind farm integration in the landscape, and the conciliation between the monuments maintenance and wind power development. This document brings together the available presentations (slides) made during this event: 1 - Conciliating landscape protection and wind power development goals in France (Marie Villot); 2 - Wind turbines: Conflicts between development goals, landscape and acceptance - Perception and criteria (Guenter Ratzbor); 3 - Bayern's wind power atlas: a planning tool which takes into account the landscape aspects (Christian Tausch); 4 - Landscape assessment in wind farms projects: what and how to do in French administrative procedures? (Bertrand Cagneaux); 5 - Methods for evaluation of landscape for wind farms projects - A French project developer's feedback (Agathe Jouneau); 6 - Landscape Assessment: Methods from German Landscape Practice (Boris Stemmer); 7 - Acceptance of Wind Turbines - Social Psychological Research (Gundula Huebner); 8 - Local consultation: who to involve, when and how? (Paola Orozco-Souel); 9 - Local acceptability: what dialogue concepts and strategies, and how to manage wind energy objection (Charles Lhermitte); 10 - Re-powering and landscape: chances and limits (Elisabeth Ferus); 11 - Wind power and cultural heritage: consultation and dialogue to succeed (Philippe Benezech); 12

  3. Planetary Landscape Geography

    Science.gov (United States)

    Hargitai, H.

    INTRODUCTION Landscape is one of the most often used category in physical ge- ography. The term "landshap" was introduced by Dutch painters in the 15-16th cen- tury. [1] The elements that build up a landscape (or environment) on Earth consists of natural (biogenic and abiogenic - lithologic, atmospheric, hydrologic) and artificial (antropogenic) factors. Landscape is a complex system of these different elements. The same lithology makes different landscapes under different climatic conditions. If the same conditions are present, the same landscape type will appear. Landscapes build up a hierarchic system and cover the whole surface. On Earth, landscapes can be classified and qualified according to their characteristics: relief forms (morphology), and its potential economic value. Aesthetic and subjective parameters can also be considered. Using the data from landers and data from orbiters we can now classify planetary landscapes (these can be used as geologic mapping units as well). By looking at a unknown landscape, we can determine the processes that created it and its development history. This was the case in the Pathfinder/Sojourner panoramas. [2]. DISCUSSION Planetary landscape evolution. We can draw a raw landscape develop- ment history by adding the different landscape building elements to each other. This has a strong connection with the planet's thermal evolution (age of the planet or the present surface materials) and with orbital parameters (distance from the central star, orbit excentricity etc). This way we can build a complex system in which we use differ- ent evolutional stages of lithologic, atmospheric, hydrologic and biogenic conditions which determine the given - Solar System or exoplanetary - landscape. Landscape elements. "Simple" landscapes can be found on asteroids: no linear horizon is present (not differentiated body, only impact structures), no atmosphere (therefore no atmospheric scattering - black sky as part of the landscape) and no

  4. Effect of exercise and protein intake on energy expenditure in adolescents.

    Science.gov (United States)

    Barenys, M; Recasens, M A; Martí-Henneberg, C; Salas-Salvadó, J

    1993-12-01

    In order to evaluate the influence of physical exercise and protein intake on Resting Metabolic Rate (RMR) and Postprandial Energy Expenditure (PEE), 16 healthy, normal-weight, 15 year-old, adolescent males at the same stage of pubertal development were studied. They were assigned to two dietary groups receiving the same energy intake (1.3 x by measured RMR) and different proportions of macronutrients (13% protein, 39% fat, 48% CHO in Group A; 30% protein, 32% fat, 38% CHO in Group B). An increase in postprandial energy expenditure, relative to basal, was observed in all individuals. The postprandial energy expenditure was higher in group B than in group A. Postprandial Post-exercise Thermogenesis (expressed as Kcal/3 h) was significantly higher in group B than group A (p hyperproteic diet followed by moderately-intensive exercise induces increases in EE and decreases in RQ in the postprandial post-exercise period and is accompanied by increase in the RMR the following day.

  5. Changing Landscapes, Changing Landscape's Story

    Czech Academy of Sciences Publication Activity Database

    Lapka, Miloslav; Cudlínová, Eva

    2003-01-01

    Roč. 28, č. 3 (2003), s. 323-328 ISSN 0142-6397. [Symposium on Sustainable Landscapes in an Enlarged Europe. Nové Hrady, 12.09.2001-14.09.2001] R&D Projects: GA MŠk ME 530 Grant - others:GA-(XE) QLK5-CT-2000-01211-SPRITE Institutional research plan: CEZ:AV0Z5039906 Keywords : Landscape stability * narrative approach * socio-economic typology Subject RIV: DO - Wilderness Conservation

  6. A Classification of Landscape Services to Support Local Landscape Planning

    Directory of Open Access Journals (Sweden)

    María Vallés-Planells

    2014-03-01

    Full Text Available The ecosystem services approach has been proven successful to measure the contributions of nature and greenery to human well-being. Ecosystems have an effect on quality of life, but landscapes also, as a broader concept, may contribute to people's well-being. The concept of landscape services, compared to ecosystem services, involves the social dimension of landscape and the spatial pattern resulting from both natural and human processes in the provision of benefits for human-well being. Our aim is to develop a classification for landscape services. The proposed typology of services is built on the Common International Classification of Ecosystem Services (CICES and on a critical review of existing literature on human well-being dimensions, existing ecosystem service classifications, and landscape perception. Three themes of landscape services are defined, each divided into several groups: provisioning, regulation and maintenance, cultural and social life fulfillment, with the latter focusing on health, enjoyment, and personal and social fulfillment. A special emphasis is made on cultural services, which are especially important when applied to landscape and which have received less attention.

  7. LANDSCAPE PLANNING IN UKRAINE: THE FIRST LANDSCAPE-PLANNING PROGRAM

    Directory of Open Access Journals (Sweden)

    Leonid Rudenko

    2013-01-01

    Full Text Available The paper presents the results of the first, in Ukraine; project on landscape planning widely accepted in European countries. Under the project implemented in 2010–2013, a landscape-planning program has been developed for the Cherkassy oblast. This is the first document of this kind in Ukraine. The program is mainly based on the experience of the German and Russian schools of landscape planning and on research and assessment conducted by the authors, which allowed identifying approaches to landscape planning, principles of the national policy, and characteristics and potential of environmentally friendly planning in Ukraine. The paper discusses the main phases of the work on the development of the landscape program for the oblast. It also identifies the main stages and key concepts and principles of landscape planning. The paper presents the results of integrated research on the identification and classification of conflicts in land use and the integral concept of the developmental goals for the oblast. The results can be the foundation for adopting management decisions and development of action plans for the lower hierarchal branches.

  8. Children with protein energy malnutrition: management and out ...

    African Journals Online (AJOL)

    Children with protein energy malnutrition: management and out-come in a ... Sahel Medical Journal ... Demographic data, predisposing factors, clinical types of PEM, outcome of management and time of discharge or death were also extracted ...

  9. Characterizing European cultural landscapes

    DEFF Research Database (Denmark)

    Tieskens, Koen F.; Schulp, Catharina J E; Levers, Christian

    2017-01-01

    intensification and land abandonment. To prevent the loss of cultural landscapes, knowledge on the location of different types of cultural landscapes is needed. In this paper, we present a characterization of European cultural landscapes based on the prevalence of three key dimensions of cultural landscapes......Almost all rural areas in Europe have been shaped or altered by humans and can be considered cultural landscapes, many of which now are considered to entail valuable cultural heritage. Current dynamics in land management have put cultural landscapes under a huge pressure of agricultural...... the three dimensions into a continuous “cultural landscape index” that allows for a characterization of Europe's rural landscapes. The characterization identifies hotspots of cultural landscapes, where all three dimensions are present, such as in the Mediterranean. On the other hand, Eastern and Northern...

  10. Free energy landscape and multiple folding pathways of an H-type RNA pseudoknot.

    Directory of Open Access Journals (Sweden)

    Yunqiang Bian

    Full Text Available How RNA sequences fold to specific tertiary structures is one of the key problems for understanding their dynamics and functions. Here, we study the folding process of an H-type RNA pseudoknot by performing a large-scale all-atom MD simulation and bias-exchange metadynamics. The folding free energy landscapes are obtained and several folding intermediates are identified. It is suggested that the folding occurs via multiple mechanisms, including a step-wise mechanism starting either from the first helix or the second, and a cooperative mechanism with both helices forming simultaneously. Despite of the multiple mechanism nature, the ensemble folding kinetics estimated from a Markov state model is single-exponential. It is also found that the correlation between folding and binding of metal ions is significant, and the bound ions mediate long-range interactions in the intermediate structures. Non-native interactions are found to be dominant in the unfolded state and also present in some intermediates, possibly hinder the folding process of the RNA.

  11. A study of the deep structure of the energy landscape of glassy polystyrene: the exponential distribution of the energy barriers revealed by high-field electron spin resonance spectroscopy

    International Nuclear Information System (INIS)

    Bercu, V; Martinelli, M; Massa, C A; Pardi, L A; Leporini, D

    2004-01-01

    The reorientation of one small paramagnetic molecule (spin probe) in glassy polystyrene (PS) is studied by high-field electron spin resonance spectroscopy at two different Larmor frequencies (190 and 285 GHz). The exponential distribution of the energy barriers for the rotational motion of the spin probe is unambiguously evidenced at both 240 and 270 K. The same shape for the distribution of the energy barriers of PS was evidenced by the master curves provided by previous mechanical and light scattering studies. The breadth of the energy barrier distribution of the spin probe is in the range of the estimates of the breadth of the PS energy barrier distribution. The evidence that the deep structure of the energy landscape of PS exhibits the exponential shape of the energy barrier distribution agrees with the results from extreme-value statistics (Bouchaud and Mezard 1997 J. Phys. A: Math. Gen. 30 7997) and the trap model by Bouchaud and co-workers (1996 J. Phys. A: Math. Gen. 29 3847, 2001 Phys. Rev. B 64 104417). (letter to the editor)

  12. Multifunctional landscape practice and accessibility in manorial landscapes

    DEFF Research Database (Denmark)

    Brandt, Jesper; Svenningsen, Stig Roar; Christensen, Andreas Aagaard

    . However classical manorial estates seems to represent an opposite trend. Allthough working at the same market conditions as other large specialized holdings developed through the process of structural rationalization, they have often maintained and elaborated a land use strategy based on a multifunctional...... use of the potential ecosystem services present within their domain. The targeted combination of agriculture, forestry, hunting rents, rental housing, and a variety of recreational activities influences makes a certain public accessibility to an integrated part of this strategy, diverging from...... the multifunctional landscape strategy supporting a certain public access. A study of this thesis is presented based on an analysis of multifunctionality, landscape development and accessibility in Danish Manorial landscapes and eventual linkages between their multifunctional landscape strategy, their history...

  13. Beyond Landscape MacArchitecture: new languages, new landscapes

    Directory of Open Access Journals (Sweden)

    Simon Rackham

    1996-03-01

    Full Text Available The sine qua non of landscape architecture is respect for the genius loci, but even in the landscape, as in architecture and society more generally, a process of cultural homogenisation has been taking place. Against this process, a resurgence of interest in minority languages in Europe can be seen as an assertion of pride, and a desire to preserve difference. In Scotland, landscape architects are attempting to reinterpret Scottish and northern European urban design influences and materials: in effect to develop a new regional dialect for the new landscapes. Rooted in sound design principles and materials which respond to and reflect the climate, way of life and traditions of the place, design languages can communicate effectively about cultural values and differences.

  14. Dynamic prestress in a globular protein.

    Directory of Open Access Journals (Sweden)

    Scott A Edwards

    Full Text Available A protein at equilibrium is commonly thought of as a fully relaxed structure, with the intra-molecular interactions showing fluctuations around their energy minimum. In contrast, here we find direct evidence for a protein as a molecular tensegrity structure, comprising a balance of tensed and compressed interactions, a concept that has been put forward for macroscopic structures. We quantified the distribution of inter-residue prestress in ubiquitin and immunoglobulin from all-atom molecular dynamics simulations. The network of highly fluctuating yet significant inter-residue forces in proteins is a consequence of the intrinsic frustration of a protein when sampling its rugged energy landscape. In beta sheets, this balance of forces is found to compress the intra-strand hydrogen bonds. We estimate that the observed magnitude of this pre-compression is enough to induce significant changes in the hydrogen bond lifetimes; thus, prestress, which can be as high as a few 100 pN, can be considered a key factor in determining the unfolding kinetics and pathway of proteins under force. Strong pre-tension in certain salt bridges on the other hand is connected to the thermodynamic stability of ubiquitin. Effective force profiles between some side-chains reveal the signature of multiple, distinct conformational states, and such static disorder could be one factor explaining the growing body of experiments revealing non-exponential unfolding kinetics of proteins. The design of prestress distributions in engineering proteins promises to be a new tool for tailoring the mechanical properties of made-to-order nanomaterials.

  15. PESP Landscaping Initiative

    Science.gov (United States)

    Landscaping practices can positively or negatively affect local environments and human health. The Landscaping Initiative seeks to enhance benefits of landscaping while reducing need for pesticides, fertilizers, etc., by working with partners.

  16. Transferable coarse-grained potential for de novo protein folding and design.

    Directory of Open Access Journals (Sweden)

    Ivan Coluzza

    Full Text Available Protein folding and design are major biophysical problems, the solution of which would lead to important applications especially in medicine. Here we provide evidence of how a novel parametrization of the Caterpillar model may be used for both quantitative protein design and folding. With computer simulations it is shown that, for a large set of real protein structures, the model produces designed sequences with similar physical properties to the corresponding natural occurring sequences. The designed sequences require further experimental testing. For an independent set of proteins, previously used as benchmark, the correct folded structure of both the designed and the natural sequences is also demonstrated. The equilibrium folding properties are characterized by free energy calculations. The resulting free energy profiles not only are consistent among natural and designed proteins, but also show a remarkable precision when the folded structures are compared to the experimentally determined ones. Ultimately, the updated Caterpillar model is unique in the combination of its fundamental three features: its simplicity, its ability to produce natural foldable designed sequences, and its structure prediction precision. It is also remarkable that low frustration sequences can be obtained with such a simple and universal design procedure, and that the folding of natural proteins shows funnelled free energy landscapes without the need of any potentials based on the native structure.

  17. Velocity landscape correlation resolves multiple flowing protein populations from fluorescence image time series.

    Science.gov (United States)

    Pandžić, Elvis; Abu-Arish, Asmahan; Whan, Renee M; Hanrahan, John W; Wiseman, Paul W

    2018-02-16

    Molecular, vesicular and organellar flows are of fundamental importance for the delivery of nutrients and essential components used in cellular functions such as motility and division. With recent advances in fluorescence/super-resolution microscopy modalities we can resolve the movements of these objects at higher spatio-temporal resolutions and with better sensitivity. Previously, spatio-temporal image correlation spectroscopy has been applied to map molecular flows by correlation analysis of fluorescence fluctuations in image series. However, an underlying assumption of this approach is that the sampled time windows contain one dominant flowing component. Although this was true for most of the cases analyzed earlier, in some situations two or more different flowing populations can be present in the same spatio-temporal window. We introduce an approach, termed velocity landscape correlation (VLC), which detects and extracts multiple flow components present in a sampled image region via an extension of the correlation analysis of fluorescence intensity fluctuations. First we demonstrate theoretically how this approach works, test the performance of the method with a range of computer simulated image series with varying flow dynamics. Finally we apply VLC to study variable fluxing of STIM1 proteins on microtubules connected to the plasma membrane of Cystic Fibrosis Bronchial Epithelial (CFBE) cells. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Protein and energy metabolism in two lines of chickens selected for growth on high or low protein diets

    DEFF Research Database (Denmark)

    Chwalibog, André; Eggum, B O; Sørensen, Peter

    1983-01-01

    Genetic adaptation was investigated in broilers selected for seven generations on a normal (A) or a low (B) protein diet. Protein and energy metabolism were studied in males from these selected lines fed on a diet of intermediate protein content. All selected birds retained more nitrogen than those...

  19. Coupling movement and landscape ecology for animal conservation in production landscapes.

    Science.gov (United States)

    Doherty, Tim S; Driscoll, Don A

    2018-01-10

    Habitat conversion in production landscapes is among the greatest threats to biodiversity, not least because it can disrupt animal movement. Using the movement ecology framework, we review animal movement in production landscapes, including areas managed for agriculture and forestry. We consider internal and external drivers of altered animal movement and how this affects navigation and motion capacities and population dynamics. Conventional management approaches in fragmented landscapes focus on promoting connectivity using structural changes in the landscape. However, a movement ecology perspective emphasizes that manipulating the internal motivations or navigation capacity of animals represents untapped opportunities to improve movement and the effectiveness of structural connectivity investments. Integrating movement and landscape ecology opens new opportunities for conservation management in production landscapes. © 2018 The Authors.

  20. Pedo-environmental evolution and agricultural landscape transformation

    Directory of Open Access Journals (Sweden)

    Gilmo Vianello

    Full Text Available Landscapes represent the stage setting of the ecosystem, the great theatre where the evolution of the environment, the changing of things and plant and animal life are played out; the diversity of landscapes derives from the combination, over time, of different environmental factors having perceptibly different roles, as in the case of climate, vegetation and human activity. Less perceptible and scarcely known is the role of soil, which has the ability not only to diversify the ecosystem’s landscapes but also to differentiate its level of productivity and liveability. The role of soil as part of the landscape is not always so evident, especially when it is covered by vegetation that precludes observation. At times, however, soils show themselves conspicuously, at least on the surface, when the colours of the epipedons invade the landscape and – in the ploughing season – dominate it. While it may be reassuring to see neatly cultivated fields and crops growing luxuriantly and homogeneously, the increasingly marked and evident signs of soil degradation or erosion are a cause for concern. In the recent past, the relationship between man and soil resources was strongly influenced by natural factors inside and outside the soil itself, socio-economic conditions and above all the labour force, i.e. the people employed in the primary sector; consequently, it was based on such factors that crop-growing choices were adapted to the different ecosystems, resulting in a diversification of rural landscapes. Starting from the second half of the twentieth century, the introduction of chemicals, mechanisation and exploitation of various forms of energy drastically transformed land use in the space of just a few years, with a logic aimed at improving the production capacity of farmland and forest land in both qualitative and quantitative terms. As a consequence, farming choices that were formerly adapted to the natural and socio-economic conditions of

  1. Pedo-environmental evolution and agricultural landscape transformation

    Directory of Open Access Journals (Sweden)

    Gilmo Vianello

    2009-10-01

    Full Text Available Landscapes represent the stage setting of the ecosystem, the great theatre where the evolution of the environment, the changing of things and plant and animal life are played out; the diversity of landscapes derives from the combination, over time, of different environmental factors having perceptibly different roles, as in the case of climate, vegetation and human activity. Less perceptible and scarcely known is the role of soil, which has the ability not only to diversify the ecosystem’s landscapes but also to differentiate its level of productivity and liveability. The role of soil as part of the landscape is not always so evident, especially when it is covered by vegetation that precludes observation. At times, however, soils show themselves conspicuously, at least on the surface, when the colours of the epipedons invade the landscape and – in the ploughing season – dominate it. While it may be reassuring to see neatly cultivated fields and crops growing luxuriantly and homogeneously, the increasingly marked and evident signs of soil degradation or erosion are a cause for concern. In the recent past, the relationship between man and soil resources was strongly influenced by natural factors inside and outside the soil itself, socio-economic conditions and above all the labour force, i.e. the people employed in the primary sector; consequently, it was based on such factors that crop-growing choices were adapted to the different ecosystems, resulting in a diversification of rural landscapes. Starting from the second half of the twentieth century, the introduction of chemicals, mechanisation and exploitation of various forms of energy drastically transformed land use in the space of just a few years, with a logic aimed at improving the production capacity of farmland and forest land in both qualitative and quantitative terms. As a consequence, farming choices that were formerly adapted to the natural and socio-economic conditions of

  2. The importance of on-site evaluation for placing renewable energy in the landscape: A case study of the Búrfell wind farm (Iceland)

    Czech Academy of Sciences Publication Activity Database

    Frantál, Bohumil; Bevk, T.; van Veelen, B.; Hărmănescu, M.; Benediktsson, K.

    2017-01-01

    Roč. 25, č. 4 (2017), s. 234-247 ISSN 1210-8812 R&D Projects: GA ČR GA16-04483S Institutional support: RVO:68145535 Keywords : wind energy * landscape perception * Iceland Subject RIV: DE - Earth Magnetism, Geodesy, Geography OBOR OECD: Environmental sciences (social aspects) Impact factor: 2.149, year: 2016 http://www.geonika.cz/EN/research/ENMGRClanky/2017_4_FRANT%C3%81L.pdf

  3. Increasing the protein content of meals and its effect on daily energy intake.

    Science.gov (United States)

    Blatt, Alexandria D; Roe, Liane S; Rolls, Barbara J

    2011-02-01

    High-protein preloads have been shown to enhance satiety, but little is known about the satiating effects of protein in more typical situations when meals are consumed ad libitum. To investigate the effects of protein in amounts commonly consumed over a day, a crossover study was conducted in 2008. In this experiment, 18 normal-weight women consumed ad libitum lunch and dinner entrées 1 day a week that were covertly varied in protein content (10%, 15%, 20%, 25%, or 30% energy). Entrées were manipulated by substituting animal protein for starchy ingredients and were matched for energy density, fat content, palatability, and appearance. Unmanipulated breakfasts and evening snacks were consumed ad libitum. Participants rated their hunger and fullness before and after meals as well as the taste and appearance of entrées. Data were analyzed using a mixed linear model. Results showed that mean 24-hour protein intake increased significantly across conditions, from 44±2 g/day in the 10% protein condition to 82±6 g/day in the 30% condition. Daily energy intake did not differ significantly across the 10% to 30% protein conditions (means 1,870±93, 1,887±93, 1,848±111, 1,876±100, and 1,807±98 kcal in the 10%, 15%, 20%, 25%, and 30% energy groups, respectively). There were no significant differences in hunger and fullness ratings across conditions or in taste and appearance ratings of the manipulated entrées. This study showed that varying the protein content of several entrées consumed ad libitum did not differentially influence daily energy intake or affect ratings of satiety. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.

  4. Irisin is Associated with Urotensin II and Protein Energy Wasting in Hemodialysis Patients

    Directory of Open Access Journals (Sweden)

    Wan-Yu He

    2016-02-01

    Full Text Available Aims/Introduction: Irisin is a newly identified myokine which can promote energy expenditure. Urotensin II (UII is identified as the most potent mammalian vasoconstrictor to date. Previous studies showed that UII can aggravate insulin resistance while irisin alleviate insulin resistance. Through this study, it is our aim to elucidate if UII can induce insulin resistance and also have an association with the irisin level in hemodialysis (HD patients. Materials and Methods: One hundred and twenty-eight patients on maintenance hemodialysis treatment and forty healthy subjects were enrolled in this study. Blood irisin concentrations and UII concentrations were measured by ELISA and RIA respectively. The body composition was analyzed by bioelectrical impedance. Results: The serum irisin levels and UII levels were both significantly lower in HD patients in comparison to that of the healthy subjects. The serum irisin levels were lower in HD patients with protein energy wasting than those of the patients without protein energy wasting. The independent determinants of circulating Ln (irisin (the natural logarithm of irisin were UII lean body mass and patients with protein energy wasting. Conclusions: Our results are the first to provide the clinical evidence of the association among irisin, UII, and protein energy wasting. Our results hint that UII and protein energy wasting might inhibit the release or synthesis of irisin from skeletal muscles in HD patients.

  5. Albumin synthesis in protein energy malnutrition

    International Nuclear Information System (INIS)

    Duggan, C.; Hardy, S.; Kleinman, R.E.; Harvard Medical School, Children's Hospital, Boston, MA; Lembcke, J.; Young, V.R.

    1996-01-01

    Assessment of protein nutritional status during re-feeding children with protein energy malnutrition (PEM) can be difficult. We hypothesized that the fractional synthesis rate (FSR) of albumin, as measured by stable isotope technology, would serve as an objective measure of changes in protein status, and that increased amounts of dietary protein (15% of calories vs 10%) would lead to higher FSR. Eight (5 M, 3 F) Peruvian children (mean age 15.5 months) with PEM (mean wt/ht Z score = -2.47) were studied twice during the first week of admission by the flooding dose technique. An intravenous dose of 13 C-leucine (57 mg/kg, 99 atom%) was given and serial blood samples were drawn in intervals up to 90 minutes in order to measure isotopic enrichment of serum albumin. Mean FSR for the day one infusion was 6.11% (range 3.07 - 15.37%) (n = 8). Mean FSR for the follow-up infusion was 7.67% (range 3.63 - 12.37%) (n = 5), and FSR was no different between the two dietary groups. FSR on day one was inversely related to age (r = -0.62), and one patient with Shigella dysentery had the highest FSR (15.9%). We conclude that FSR of albumin can be measured successfully in children with PEM using the flooding dose technique, and that assessment of albumin FSR holds promise to help determine protein requirements and status during recovery from PEM. (author). 14 refs, 6 figs, 3 tabs

  6. Albumin synthesis in protein energy malnutrition

    Energy Technology Data Exchange (ETDEWEB)

    Duggan, C; Hardy, S; Kleinman, R E [Massachusetts General Hospital, Boston, MA (United States); [Harvard Medical School, Children` s Hospital, Boston, MA (United States). Combined Program in Pediatric GI and Nutrition; Lembcke, J [Av. La Universidad S/N - La Molina, Lima (Peru). Inst. de Investigacion Nutricional; Young, V R [Massachussetts Inst. of Technology, Cambridge, MA (United States). Lab. of Human Nutrition

    1997-12-31

    Assessment of protein nutritional status during re-feeding children with protein energy malnutrition (PEM) can be difficult. We hypothesized that the fractional synthesis rate (FSR) of albumin, as measured by stable isotope technology, would serve as an objective measure of changes in protein status, and that increased amounts of dietary protein (15% of calories vs 10%) would lead to higher FSR. Eight (5 M, 3 F) Peruvian children (mean age 15.5 months) with PEM (mean wt/ht Z score = -2.47) were studied twice during the first week of admission by the flooding dose technique. An intravenous dose of {sup 13}C-leucine (57 mg/kg, 99 atom%) was given and serial blood samples were drawn in intervals up to 90 minutes in order to measure isotopic enrichment of serum albumin. Mean FSR for the day one infusion was 6.11% (range 3.07 - 15.37%) (n = 8). Mean FSR for the follow-up infusion was 7.67% (range 3.63 - 12.37%) (n = 5), and FSR was no different between the two dietary groups. FSR on day one was inversely related to age (r = -0.62), and one patient with Shigella dysentery had the highest FSR (15.9%). We conclude that FSR of albumin can be measured successfully in children with PEM using the flooding dose technique, and that assessment of albumin FSR holds promise to help determine protein requirements and status during recovery from PEM. (author). 14 refs, 6 figs, 3 tabs.

  7. Increased protein intake and meal frequency reduces abdominal fat during energy balance and energy deficit.

    Science.gov (United States)

    Arciero, Paul J; Ormsbee, Michael J; Gentile, Christopher L; Nindl, Bradley C; Brestoff, Jonathan R; Ruby, Maxwell

    2013-07-01

    Unrefined, complex carbohydrates and lean protein diets are used to combat obesity, although it's unknown whether more frequent meals may improve this response. The effects of consuming traditional (~15%) versus higher (~35%) protein intakes as three or six meals/day on abdominal fat, postprandial thermogenesis (TEM), and cardiometabolic biomarkers in overweight individuals during 28 days of energy balance (BAL) and deficit (NEG), respectively were compared. Overweight individuals (n = 30) were randomized into three groups: two high-protein groups (35% of energy) consumed as three (HP3) or six (HP6) meals/day and one group consumed three meals/day of a traditional intake (TD3). Following a 5-day baseline control (CON), subjects consumed their respective diets throughout a 56-day intervention consisting of two, 28 day phases: a BAL followed by a NEG phase (75% of energy needs). Total body fat (BF) and abdominal BF (ABF), body weight (BW), TEM, and fasting biomarkers were assessed at the end of CON, BAL, and NEG phases. BW remained stable throughout CON and BAL in all groups, whereas BF (P meals/day in overweight individuals during both BAL and NEG. Copyright © 2013 The Obesity Society.

  8. Colloids exposed to random potential energy landscapes: From particle number density to particle-potential and particle-particle interactions

    International Nuclear Information System (INIS)

    Bewerunge, Jörg; Capellmann, Ronja F.; Platten, Florian; Egelhaaf, Stefan U.; Sengupta, Ankush; Sengupta, Surajit

    2016-01-01

    Colloidal particles were exposed to a random potential energy landscape that has been created optically via a speckle pattern. The mean particle density as well as the potential roughness, i.e., the disorder strength, were varied. The local probability density of the particles as well as its main characteristics were determined. For the first time, the disorder-averaged pair density correlation function g (1) (r) and an analogue of the Edwards-Anderson order parameter g (2) (r), which quantifies the correlation of the mean local density among disorder realisations, were measured experimentally and shown to be consistent with replica liquid state theory results.

  9. Landscapes for Energy and Wildlife: Conservation Prioritization for Golden Eagles across Large Spatial Scales.

    Directory of Open Access Journals (Sweden)

    Jason D Tack

    Full Text Available Proactive conservation planning for species requires the identification of important spatial attributes across ecologically relevant scales in a model-based framework. However, it is often difficult to develop predictive models, as the explanatory data required for model development across regional management scales is rarely available. Golden eagles are a large-ranging predator of conservation concern in the United States that may be negatively affected by wind energy development. Thus, identifying landscapes least likely to pose conflict between eagles and wind development via shared space prior to development will be critical for conserving populations in the face of imposing development. We used publically available data on golden eagle nests to generate predictive models of golden eagle nesting sites in Wyoming, USA, using a suite of environmental and anthropogenic variables. By overlaying predictive models of golden eagle nesting habitat with wind energy resource maps, we highlight areas of potential conflict among eagle nesting habitat and wind development. However, our results suggest that wind potential and the relative probability of golden eagle nesting are not necessarily spatially correlated. Indeed, the majority of our sample frame includes areas with disparate predictions between suitable nesting habitat and potential for developing wind energy resources. Map predictions cannot replace on-the-ground monitoring for potential risk of wind turbines on wildlife populations, though they provide industry and managers a useful framework to first assess potential development.

  10. LANDSCAPE ECOLOGICAL METHOD TO STUDY AGRICULTURAL VEGETATION: SOME EXAMPLES FROM THE PO VALLEY

    Directory of Open Access Journals (Sweden)

    E. GIGLIO

    2006-01-01

    Full Text Available Vegetation is the most important landscape component, as regards to its ability to catch solar energy and to transform it, but also to shape the landscape, to structure the space, to create the fit environment for different animal species, to contribute to the maintenance of a correct metastability level for the landscape, etc. It is a biological system which acts under the constraints of the principles of the System Theory and owns the same properties of any other living system: so, it is a complex adaptive, hierarchical, dynamic, dissipative, self-organizing, self-transcendent, autocatalytic, self-maintaining system and follows the non-equilibrium thermodynamic. Its ecological state can be investigated through the comparison between “gathered data” (pathology and “normal data” (physiology for analogous types of vegetation. The Biological Integrated School of Landscape Ecology provides an integrated methodology to define ecological threshold limits of the different Agricultural Landscape types and applies to agricultural vegetation the specific part of the new methodology already tested to studying forests (the Landscape Biological Survey of Vegetation. Ecological quality, better and worst parameters, biological territorial capacity of vegetated corridors, agricultural field, poplar groves, orchards and woody remnant patches are investigated. Some examples from diverse agricultural landscapes of the Po Valley will be discussed. KEY WORDS: agricultural landscape, vegetation, landscape ecology, landscape health, Biological Integrated Landscape Ecology, Landscape Biological Survey of vegetation.

  11. LANDSCAPE ECOLOGICAL METHOD TO STUDY AGRICULTURAL VEGETATION: SOME EXAMPLES FROM THE PO VALLEY

    Directory of Open Access Journals (Sweden)

    E. GIGLIO

    2006-05-01

    Full Text Available Vegetation is the most important landscape component, as regards to its ability to catch solar energy and to transform it, but also to shape the landscape, to structure the space, to create the fit environment for different animal species, to contribute to the maintenance of a correct metastability level for the landscape, etc. It is a biological system which acts under the constraints of the principles of the System Theory and owns the same properties of any other living system: so, it is a complex adaptive, hierarchical, dynamic, dissipative, self-organizing, self-transcendent, autocatalytic, self-maintaining system and follows the non-equilibrium thermodynamic. Its ecological state can be investigated through the comparison between “gathered data” (pathology and “normal data” (physiology for analogous types of vegetation. The Biological Integrated School of Landscape Ecology provides an integrated methodology to define ecological threshold limits of the different Agricultural Landscape types and applies to agricultural vegetation the specific part of the new methodology already tested to studying forests (the Landscape Biological Survey of Vegetation. Ecological quality, better and worst parameters, biological territorial capacity of vegetated corridors, agricultural field, poplar groves, orchards and woody remnant patches are investigated. Some examples from diverse agricultural landscapes of the Po Valley will be discussed. KEY WORDS: agricultural landscape, vegetation, landscape ecology, landscape health, Biological Integrated Landscape Ecology, Landscape Biological Survey of vegetation.

  12. Thermodynamic free energy methods to investigate shape transitions in bilayer membranes.

    Science.gov (United States)

    Ramakrishnan, N; Tourdot, Richard W; Radhakrishnan, Ravi

    2016-06-01

    The conformational free energy landscape of a system is a fundamental thermodynamic quantity of importance particularly in the study of soft matter and biological systems, in which the entropic contributions play a dominant role. While computational methods to delineate the free energy landscape are routinely used to analyze the relative stability of conformational states, to determine phase boundaries, and to compute ligand-receptor binding energies its use in problems involving the cell membrane is limited. Here, we present an overview of four different free energy methods to study morphological transitions in bilayer membranes, induced either by the action of curvature remodeling proteins or due to the application of external forces. Using a triangulated surface as a model for the cell membrane and using the framework of dynamical triangulation Monte Carlo, we have focused on the methods of Widom insertion, thermodynamic integration, Bennett acceptance scheme, and umbrella sampling and weighted histogram analysis. We have demonstrated how these methods can be employed in a variety of problems involving the cell membrane. Specifically, we have shown that the chemical potential, computed using Widom insertion, and the relative free energies, computed using thermodynamic integration and Bennett acceptance method, are excellent measures to study the transition from curvature sensing to curvature inducing behavior of membrane associated proteins. The umbrella sampling and WHAM analysis has been used to study the thermodynamics of tether formation in cell membranes and the quantitative predictions of the computational model are in excellent agreement with experimental measurements. Furthermore, we also present a method based on WHAM and thermodynamic integration to handle problems related to end-point-catastrophe that are common in most free energy methods.

  13. Protein and energy intake improved by breakfast intervention in hospital.

    Science.gov (United States)

    Beermann, T; Mortensen, M N; Skadhauge, L B; Høgsted, R H; Rasmussen, H H; Holst, Mette

    2016-06-01

    Undernutrition affects about 40% of patients in hospitals. Ordinary food is recommended as the first choice to prevent and correct undernutrition. Meanwhile, sufficient intake, especially regarding protein, is difficult to reach, in patients at nutritional risk. The aim of this study was to improve protein intake at breakfast to at least 20% of total daily requirement or at least 20 g. A protein rich breakfast including 20 g of protein was served in the departments of heart and lung surgery and vascular surgery for three months. Nutrition intake was registered before and after intervention. Food intake records were collected from 32 and 30 patients respectively, mean age 69 (SD 8) years. At breakfast, protein intake was improved from 14% of individual requirements to 22% (penergy intake was improved from 18% to 25% (p=0.01). Total amount of protein intake for breakfast was increased from 14 g to 20 g (pprotein intake increased from 64% to 77% (p=0.05) and total energy intake from 76% to 99% (pProtein and energy intake for surgical patients at breakfast as well as total daily intake was significantly increased to meet recommended average level for minimum individually measured requirements. Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

  14. Understanding the whole city as landscape. A multivariate approach to urban landscape morphology

    Directory of Open Access Journals (Sweden)

    Richard Stiles

    2014-05-01

    Full Text Available The European Landscape Convention implies a requirement for signatory states to identify their urban landscapes which goes beyond the traditional focus on individual parks and green spaces and the links between them. Landscape ecological approaches can provide a useful model for identifying urban landscape types across a whole territory, but the variables relevant for urban landscapes are very different to those usually addressing rural areas. This paper presents an approach to classifying the urban landscape of Vienna that was developed in a research project funded by the Austrian Ministry for Transport, Innovation and Technology: ‘Urban Fabric and Microclimate Response’. Nine landscape types and a number of sub-types were defined, using a multivariate statistical approach which takes account of both morphological and urban climate related variables. Although the variables were selected to objectively reflect the factors that could best represent the urban climatic characteristics of the urban landscape, the results also provided a widely plausible representation of the structure of the city’s landscapes. Selected examples of the landscape types that were defined in this way were used both to simulate current microclimatic conditions and also to model the effects of possible climatic amelioration measures. Finally the paper looks forward to developing a more general-purpose urban landscape typology that allows investigating a much broader complex of urban landscape functions.

  15. Energy from biomass. Ethics and practice; Energie aus Biomasse. Ethik und Praxis

    Energy Technology Data Exchange (ETDEWEB)

    Franke, Silke [ed.

    2013-06-01

    The implementation of the energy policy turnaround inevitably results in modifications of the land use and landscape. Besides the discussion about the environmental consequences, a debate about ethical issues increasingly arose. Under this aspect, the booklet under consideration contains the following contributions: (1) Renewable energy sources - the role of bioenergy (Bernard Widmann); (2) Energy from biomass - An ethic analysis (Stephan Schleissing); (3) Culture for our landscapes - combination of biomass and water protection (Frank Wagener); (4) Cultivation of energy crops - short rotation coppices (Frank Burger); (5) Bioenergy region Straubing-Bogen: Excellent in the matter of renewable energy sources (Josefine Eichwald); (6) Rural development - motor for the energy policy turnaround (Roland Spiller).

  16. Intuitive Density Functional Theory-Based Energy Decomposition Analysis for Protein-Ligand Interactions.

    Science.gov (United States)

    Phipps, M J S; Fox, T; Tautermann, C S; Skylaris, C-K

    2017-04-11

    First-principles quantum mechanical calculations with methods such as density functional theory (DFT) allow the accurate calculation of interaction energies between molecules. These interaction energies can be dissected into chemically relevant components such as electrostatics, polarization, and charge transfer using energy decomposition analysis (EDA) approaches. Typically EDA has been used to study interactions between small molecules; however, it has great potential to be applied to large biomolecular assemblies such as protein-protein and protein-ligand interactions. We present an application of EDA calculations to the study of ligands that bind to the thrombin protein, using the ONETEP program for linear-scaling DFT calculations. Our approach goes beyond simply providing the components of the interaction energy; we are also able to provide visual representations of the changes in density that happen as a result of polarization and charge transfer, thus pinpointing the functional groups between the ligand and protein that participate in each kind of interaction. We also demonstrate with this approach that we can focus on studying parts (fragments) of ligands. The method is relatively insensitive to the protocol that is used to prepare the structures, and the results obtained are therefore robust. This is an application to a real protein drug target of a whole new capability where accurate DFT calculations can produce both energetic and visual descriptors of interactions. These descriptors can be used to provide insights for tailoring interactions, as needed for example in drug design.

  17. Urban landscape infrastructures: Designing operative landscape structures for the built environment

    OpenAIRE

    Nijhuis, S.; Jauslin, D.T.

    2015-01-01

    This paper explores infrastructure as a type of landscape and landscape as a type of infrastructure. The hybridisation of the two concepts, landscape and infrastructure, seeks to redefine infrastructure beyond its strictly utilitarian definition, while allowing design disciplines to gain operative force in territorial transformation processes. This paper aims to put forward urban landscape infrastructures as a design concept, considering them as armatures for urban development and for facilit...

  18. A review of some metabolic changes in protein-energy malnutrition.

    Science.gov (United States)

    Akuyam, S A

    2007-06-01

    Protein-energy malnutrition (PEM) is a major public health problem in the tropical and subtropical regions of the world and often arises during protein and / or energy deficit due to nutritional inadequacy, infections and poor socio-economic and environmental conditions. It is the most common nutritional disorder affecting children in developing countries and the third most common disease of childhood in such countries. PEM has a lasting effect on immune functions, growth and development of children, learning ability, social adjustment, work efficiency and productivity of labour. It seems that many deaths from PEM occur as a result of outdated clinical practices and that improving these practices reduces the rate of morbidity and mortality. This paper reviews various metabolic changes in protein-energy malnutrition (PEM). It gives an overview of the theoretical basis for the understanding of the biochemical derangements in PEM. It aims at stimulating the paediatricians and clinical chemists to read more on the recent advances in this broad subject with the view to improving the understanding of the current laboratory investigation of PEM. This review demonstrates that the metabolic changes in PEM include water and electrolytes imbalance, amino acids and proteins deficiencies, carbohydrates and energy deficiencies, hypolipidaemias, hypolipoproteinaemias, hormonal imbalance, deficiency of anti-oxidant vitamins and enzymes, depression of cell-mediated immune complexes and decrease in amino acids and trace elements in skin and hair. The review therefore suggests that assessment of these conditions in PEM patients could improve the management of this group of patients and hence reduce the rate of morbidity and mortality from PEM.

  19. Contemporary danish landscape research

    DEFF Research Database (Denmark)

    Vejre, H.; Brandt, J.

    2004-01-01

    Danish landscape research blossomed during the 1990’ies thanks to several transdisciplinary research programmes involving several institutions. The main themes of the programmes encompassed Landscape change, landscape and biological diversity, nature and landscape management, use and monitoring...

  20. Alternative prediction methods of protein and energy evaluation of pig feeds.

    Science.gov (United States)

    Święch, Ewa

    2017-01-01

    Precise knowledge of the actual nutritional value of individual feedstuffs and complete diets for pigs is important for efficient livestock production. Methods of assessment of protein and energy values in pig feeds have been briefly described. In vivo determination of protein and energy values of feeds in pigs are time-consuming, expensive and very often require the use of surgically-modified animals. There is a need for more simple, rapid, inexpensive and reproducible methods for routine feed evaluation. Protein and energy values of pig feeds can be estimated using the following alternative methods: 1) prediction equations based on chemical composition; 2) animal models as rats, cockerels and growing pigs for adult animals; 3) rapid methods, such as the mobile nylon bag technique and in vitro methods. Alternative methods developed for predicting the total tract and ileal digestibility of nutrients including amino acids in feedstuffs and diets for pigs have been reviewed. This article focuses on two in vitro methods that can be used for the routine evaluation of amino acid ileal digestibility and energy value of pig feeds and on factors affecting digestibility determined in vivo in pigs and by alternative methods. Validation of alternative methods has been carried out by comparing the results obtained using these methods with those acquired in vivo in pigs. In conclusion, energy and protein values of pig feeds may be estimated with satisfactory precision in rats and by the two- or three-step in vitro methods providing equations for the calculation of standardized ileal digestibility of amino acids and metabolizable energy content. The use of alternative methods of feed evaluation is an important way for reduction of stressful animal experiments.

  1. The German energy landscape in 2015

    International Nuclear Information System (INIS)

    Lauer, Hartmut

    2016-01-01

    This article proposes a brief overview of the German energy sector: stagnation of primary energy consumption, shares of the different energy sources (renewable, coal, lignite, oil, gas, nuclear), shares of the different electric power production sources and their recent evolution. It evokes issues related to the objectives defined for energy transition, the high level of renewable energy production and the high level of power exports. It outlines that consumption must be reduced to reach the objectives defined for 2020. It notices a stagnation of the energy system de-carbonation, and comments the evolution of electricity prices

  2. Responding to Landscape Change: Stakeholder Participation and Social Capital in Five European Landscapes

    Directory of Open Access Journals (Sweden)

    Thanasis Kizos

    2018-01-01

    Full Text Available The concept of landscape has been increasingly used, in the last decades, in policy and land use planning, both in regard to so-called “special” and to “ordinary” or “everyday” landscapes. This has raised the importance of local and public participation in all issues that refer to landscapes and the definition of the groups that “have a stake” in the landscape. In this paper, we provide insights into how stakeholders perceive the dynamics of local processes of landscape change (and continuity and which processes of landscape change they perceive as important, in positive and negative ways, from five communities within the European Union. These landscapes involve different landscape issues “at stake”, different national and local planning and decision-making traditions and practices, and varying degrees of engagement. The understanding of these complexities and the unraveling of the insights is done through the concept of social capital and its different forms. We report on three series of workshops that have been organized to discuss landscape issues and approaches or ideas for landscape management. We witnessed interactions between the different stakeholders and gained insights into how social capital affects landscape change. We found that despite differences, similarities emerged concerning the interplay between “expert” and “local” knowledge and between “insideness” and “outsideness”. Social capital plays an important part, as it provides the template for personal and collective evaluation of landscape changes, who should manage these changes and how they should be managed. These findings are important to develop in-depth insights on dynamics and values of cultural landscapes and visions for re-coupling social and ecological components in cultural landscapes and translate them into policy and management options.

  3. Urban landscape infrastructures : Designing operative landscape structures for the built environment

    NARCIS (Netherlands)

    Nijhuis, S.; Jauslin, D.T.

    2015-01-01

    This paper explores infrastructure as a type of landscape and landscape as a type of infrastructure. The hybridisation of the two concepts, landscape and infrastructure, seeks to redefine infrastructure beyond its strictly utilitarian definition, while allowing design disciplines to gain operative

  4. Effect of bacterial protein meal on protein and energy metabolism in growing chickens

    DEFF Research Database (Denmark)

    Hellwing, Anne Louise Frydendahl; Tauson, Anne-Helene; Skrede, Anders

    2006-01-01

    This experiment investigates the effect of increasing the dietary content of bacterial protein meal (BPM) on the protein and energy metabolism, and carcass chemical composition of growing chickens. Seventy-two Ross male chickens were allocated to four diets, each in three replicates with 0% (D0), 2...... (period 1), 5 chickens (period 2), and one chicken (periods 3-5). After each balance period, one chicken in each cage was killed and the carcass weight was recorded. Chemical Analyses were performed on the carcasses from periods, 1, 3, and 5. Weight gain, feed intake, and feed conversion rate were found...... to be similar for all diets. Chickens on D0 retained 1.59 g N·kg-°75·d-¹, respectively. This was probably caused by the higher nitrogen content of D0. Neither the HE (p=0.92) nor the retention of energy (P=0.88) were affected by diet. Carcass composition was similar between diets, in line with the values...

  5. Prediction of hot spot residues at protein-protein interfaces by combining machine learning and energy-based methods

    Directory of Open Access Journals (Sweden)

    Pontil Massimiliano

    2009-10-01

    Full Text Available Abstract Background Alanine scanning mutagenesis is a powerful experimental methodology for investigating the structural and energetic characteristics of protein complexes. Individual amino-acids are systematically mutated to alanine and changes in free energy of binding (ΔΔG measured. Several experiments have shown that protein-protein interactions are critically dependent on just a few residues ("hot spots" at the interface. Hot spots make a dominant contribution to the free energy of binding and if mutated they can disrupt the interaction. As mutagenesis studies require significant experimental efforts, there is a need for accurate and reliable computational methods. Such methods would also add to our understanding of the determinants of affinity and specificity in protein-protein recognition. Results We present a novel computational strategy to identify hot spot residues, given the structure of a complex. We consider the basic energetic terms that contribute to hot spot interactions, i.e. van der Waals potentials, solvation energy, hydrogen bonds and Coulomb electrostatics. We treat them as input features and use machine learning algorithms such as Support Vector Machines and Gaussian Processes to optimally combine and integrate them, based on a set of training examples of alanine mutations. We show that our approach is effective in predicting hot spots and it compares favourably to other available methods. In particular we find the best performances using Transductive Support Vector Machines, a semi-supervised learning scheme. When hot spots are defined as those residues for which ΔΔG ≥ 2 kcal/mol, our method achieves a precision and a recall respectively of 56% and 65%. Conclusion We have developed an hybrid scheme in which energy terms are used as input features of machine learning models. This strategy combines the strengths of machine learning and energy-based methods. Although so far these two types of approaches have mainly been

  6. Impact of the lipid bilayer on energy transfer kinetics in the photosynthetic protein LH2.

    Science.gov (United States)

    Ogren, John I; Tong, Ashley L; Gordon, Samuel C; Chenu, Aurélia; Lu, Yue; Blankenship, Robert E; Cao, Jianshu; Schlau-Cohen, Gabriela S

    2018-03-28

    Photosynthetic purple bacteria convert solar energy to chemical energy with near unity quantum efficiency. The light-harvesting process begins with absorption of solar energy by an antenna protein called Light-Harvesting Complex 2 (LH2). Energy is subsequently transferred within LH2 and then through a network of additional light-harvesting proteins to a central location, termed the reaction center, where charge separation occurs. The energy transfer dynamics of LH2 are highly sensitive to intermolecular distances and relative organizations. As a result, minor structural perturbations can cause significant changes in these dynamics. Previous experiments have primarily been performed in two ways. One uses non-native samples where LH2 is solubilized in detergent, which can alter protein structure. The other uses complex membranes that contain multiple proteins within a large lipid area, which make it difficult to identify and distinguish perturbations caused by protein-protein interactions and lipid-protein interactions. Here, we introduce the use of the biochemical platform of model membrane discs to study the energy transfer dynamics of photosynthetic light-harvesting complexes in a near-native environment. We incorporate a single LH2 from Rhodobacter sphaeroides into membrane discs that provide a spectroscopically amenable sample in an environment more physiological than detergent but less complex than traditional membranes. This provides a simplified system to understand an individual protein and how the lipid-protein interaction affects energy transfer dynamics. We compare the energy transfer rates of detergent-solubilized LH2 with those of LH2 in membrane discs using transient absorption spectroscopy and transient absorption anisotropy. For one key energy transfer step in LH2, we observe a 30% enhancement of the rate for LH2 in membrane discs compared to that in detergent. Based on experimental results and theoretical modeling, we attribute this difference to

  7. Drug disposition in obesity and protein-energy malnutrition.

    Science.gov (United States)

    Boullata, Joseph I

    2010-11-01

    Clinical response to medication can differ between patients. Among the known sources of variability is an individual's nutrition status. This review defines some pharmacokinetic terms, provides relevant body size metrics and describes the physiologic influences of protein-energy malnutrition and obesity on drug disposition. Weight-based drug dosing, which presumes a healthy BMI, can be problematic in the protein-energy malnourished or obese patient. The use of total body weight, lean body weight, or an adjusted body weight depends on the drug and how it is differently handled in malnutrition or obesity. Most of the recognized influences are seen in drug distribution and drug elimination as a result of altered body composition and function. Distribution characteristics of each drug are determined by several drug-related factors (e.g. tissue affinity) in combination with body-related factors (e.g. composition). Drug elimination occurs through metabolic and excretory pathways that can also vary with body composition. The current data are limited to select drugs that have been reported in small studies or case reports. In the meantime, a rational approach to evaluate the potential influences of malnutrition and obesity can be used clinically based on available information. Antimicrobials are discussed as a useful example of this approach. Further advancement in this field would require collaboration between experts in body composition and those in drug disposition. Until more data are available, routine monitoring by the clinician of the protein-energy malnourished or obese patient receiving weight-based drug regimens is necessary.

  8. Integrated analysis of the effects of agricultural management on nitrogen fluxes at landscape scale

    Energy Technology Data Exchange (ETDEWEB)

    Kros, J., E-mail: hans.kros@wur.nl [Alterra, Wageningen University and Research Centre, P.O. Box 47, 6700 AA Wageningen (Netherlands); Frumau, K.F.A.; Hensen, A. [Energy Research Centre of The Netherlands, P.O. Box 1, 1755 ZG Petten (Netherlands); Vries, W. de [Alterra, Wageningen University and Research Centre, P.O. Box 47, 6700 AA Wageningen (Netherlands); Environmental Systems Analysis Group, Wageningen University, P.O. Box 47, 6700 AA Wageningen (Netherlands)

    2011-11-15

    The integrated modelling system INITIATOR was applied to a landscape in the northern part of the Netherlands to assess current nitrogen fluxes to air and water and the impact of various agricultural measures on these fluxes, using spatially explicit input data on animal numbers, land use, agricultural management, meteorology and soil. Average model results on NH{sub 3} deposition and N concentrations in surface water appear to be comparable to observations, but the deviation can be large at local scale, despite the use of high resolution data. Evaluated measures include: air scrubbers reducing NH{sub 3} emissions from poultry and pig housing systems, low protein feeding, reduced fertilizer amounts and low-emission stables for cattle. Low protein feeding and restrictive fertilizer application had the largest effect on both N inputs and N losses, resulting in N deposition reductions on Natura 2000 sites of 10% and 12%, respectively. - Highlights: > We model nitrogen fluxes and the impact of agricultural measures in a rural landscape. > Average model results appear to be comparable to observations. > The measures low protein feeding and restrictive fertilizer application had the largest effect. - Effects of agricultural management on N losses to air and water are evaluated at landscape scale combining a model assessment and measurements.

  9. Efficient sampling over rough energy landscapes with high barriers: A combination of metadynamics with integrated tempering sampling

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Y. Isaac [Institute of Theoretical and Computational Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871 (China); Zhang, Jun; Che, Xing; Yang, Lijiang; Gao, Yi Qin, E-mail: gaoyq@pku.edu.cn [Institute of Theoretical and Computational Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871 (China); Biodynamic Optical Imaging Center, Peking University, Beijing 100871 (China)

    2016-03-07

    In order to efficiently overcome high free energy barriers embedded in a complex energy landscape and calculate overall thermodynamics properties using molecular dynamics simulations, we developed and implemented a sampling strategy by combining the metadynamics with (selective) integrated tempering sampling (ITS/SITS) method. The dominant local minima on the potential energy surface (PES) are partially exalted by accumulating history-dependent potentials as in metadynamics, and the sampling over the entire PES is further enhanced by ITS/SITS. With this hybrid method, the simulated system can be rapidly driven across the dominant barrier along selected collective coordinates. Then, ITS/SITS ensures a fast convergence of the sampling over the entire PES and an efficient calculation of the overall thermodynamic properties of the simulation system. To test the accuracy and efficiency of this method, we first benchmarked this method in the calculation of ϕ − ψ distribution of alanine dipeptide in explicit solvent. We further applied it to examine the design of template molecules for aromatic meta-C—H activation in solutions and investigate solution conformations of the nonapeptide Bradykinin involving slow cis-trans isomerizations of three proline residues.

  10. The Roles of Structural Order and Intermolecular Interactions in Determining Ionization Energies and Charge-Transfer State Energies in Organic Semiconductors

    KAUST Repository

    Graham, Kenneth; Ngongang Ndjawa, Guy Olivier; Conron, Sarah M.; Munir, Rahim; Vandewal, Koen; Chen, John J.; Sweetnam, Sean; Thompson, Mark E.; Salleo, Alberto; Mcgehee, Michael D.; Amassian, Aram

    2016-01-01

    The energy landscape in organic semiconducting materials greatly influences charge and exciton behavior, which are both critical to the operation of organic electronic devices. These energy landscapes can change dramatically depending on the phases

  11. Energy Savers--Tips on Saving Energy and Money at Home (Fifth Printing)

    International Nuclear Information System (INIS)

    DOE Office of Building Technology, State and Community Programs

    2001-01-01

    Provides consumers with home energy and money savings tips such as insulation, weatherization, heating, cooling, water heating, energy efficient windows, landscaping, lighting, and energy efficient appliances

  12. Energy Savers---Tips on Saving Energy and Money at Home (Fifth Printing)

    Energy Technology Data Exchange (ETDEWEB)

    DOE Office of Building Technology, State and Community Programs

    2001-08-13

    Provides consumers with home energy and money savings tips such as insulation, weatherization, heating, cooling, water heating, energy efficient windows, landscaping, lighting, and energy efficient appliances.

  13. Structure-Energy Relationships of Halogen Bonds in Proteins.

    Science.gov (United States)

    Scholfield, Matthew R; Ford, Melissa Coates; Carlsson, Anna-Carin C; Butta, Hawera; Mehl, Ryan A; Ho, P Shing

    2017-06-06

    The structures and stabilities of proteins are defined by a series of weak noncovalent electrostatic, van der Waals, and hydrogen bond (HB) interactions. In this study, we have designed and engineered halogen bonds (XBs) site-specifically to study their structure-energy relationship in a model protein, T4 lysozyme. The evidence for XBs is the displacement of the aromatic side chain toward an oxygen acceptor, at distances that are equal to or less than the sums of their respective van der Waals radii, when the hydroxyl substituent of the wild-type tyrosine is replaced by a halogen. In addition, thermal melting studies show that the iodine XB rescues the stabilization energy from an otherwise destabilizing substitution (at an equivalent noninteracting site), indicating that the interaction is also present in solution. Quantum chemical calculations show that the XB complements an HB at this site and that solvent structure must also be considered in trying to design molecular interactions such as XBs into biological systems. A bromine substitution also shows displacement of the side chain, but the distances and geometries do not indicate formation of an XB. Thus, we have dissected the contributions from various noncovalent interactions of halogens introduced into proteins, to drive the application of XBs, particularly in biomolecular design.

  14. Engineering Designed Proteins for Light Capture, Energy Transfer, and Emissive Sensing In Vivo

    Science.gov (United States)

    Mancini, Joshua A.

    Proteins that are used for photosynthetic light harvesting and biological signaling are critical to life. These types of proteins act as scaffolds that hold small, sometimes metal-containing organic molecules in precise locations for light absorption and successive use. For signaling proteins, this energy can be used to induce a photoisomerization of the small molecule that can turn on or off a signaling cascade that controls the physiology of an organism. Alternatively, photosynthetic light-harvesting proteins funnel this energy in a directional manner towards a charge separating catalytic component that can change this light energy into chemical energy. The protein environment also serves to tune the photophysical properties of the small molecules. This is seen extensively with the linear tetrapyrroles that are used in both photosynthetic and signaling proteins. Many efforts have been made to harness these natural proteins for societal use, including improving photophysical properties and interfacing capabilities with manmade catalytic components. Several methods of achieving improvement have entailed structurally guided mutation and directed evolution. However, these methods all have their limitations due to the inherent complexity and fragility of the natural proteins. This work presents an alternative more robust method to natural proteins. My thesis states: that man-made proteins, known as maquettes, employing basic rules of protein folding, can be designed to become light harvesting and signaling proteins that can be assembled fully in vivo providing an alternative, robust, and versatile platform for meeting the diverse array of societal "green chemistry" and biomedical needs. This in vivo assembly is carried out by interacting with cyanobacterial protein and pigment machinery, both as stand-alone units and as protein fusions with natural antenna complexes. Additionally, this work offers insight for fast and tight binding of circular and linear tetrapyrroles

  15. The Swiss Energy Sector. Innovation landscape and chances for the Netherlands; De Zwitserse energiesector. Innovatielandschap en kansen voor Nederland

    Energy Technology Data Exchange (ETDEWEB)

    Van Ewijk, S. [Innovatie Attache Netwerk, Ambassad Berlijn, Berlin (Netherlands)

    2012-08-15

    An overview is given of innovation in the Swiss energy sector and the following research question will be answered: what are the characteristics of the Swiss innovation landscape in the energy sector and what opportunities are there for the Dutch energy sector? The emphasis is on themes that occur in the Dutch top sector policy, such as natural gas and energy conservation. The aim is to encourage cooperation between the Netherlands and Switzerland in the field of energy and provide inspiration for investment, policy solutions and markets in the field of energy. Each chapter contains references to Swiss authorities for more information and further steps [Dutch] Een overzicht wordt gegeven van innovatie in de Zwitserse energiesector en probeert de volgende onderzoeksvraag te beantwoorden: wat zijn de kenmerken van het Zwitserse innovatielandschap in de energiesector en welke kansen zijn er voor de Nederlandse energiesector? De nadruk ligt daarbij op thema's die ook in het Nederlandse topsectorbeleid voorkomen, zoals aardgas en energiebesparing. Het doel is om de samenwerking tussen Nederland en Zwitserland op energiegebied te stimuleren en informatie te bieden als inspiratie voor investeringen, beleidsoplossingen en afzetmarkten op energiegebied. Ieder hoofdstuk bevat verwijzingen naar Zwitserse instanties voor meer informatie en verdere stappen.

  16. Exploration of the dynamic properties of protein complexes predicted from spatially constrained protein-protein interaction networks.

    Directory of Open Access Journals (Sweden)

    Eric A Yen

    2014-05-01

    Full Text Available Protein complexes are not static, but rather highly dynamic with subunits that undergo 1-dimensional diffusion with respect to each other. Interactions within protein complexes are modulated through regulatory inputs that alter interactions and introduce new components and deplete existing components through exchange. While it is clear that the structure and function of any given protein complex is coupled to its dynamical properties, it remains a challenge to predict the possible conformations that complexes can adopt. Protein-fragment Complementation Assays detect physical interactions between protein pairs constrained to ≤8 nm from each other in living cells. This method has been used to build networks composed of 1000s of pair-wise interactions. Significantly, these networks contain a wealth of dynamic information, as the assay is fully reversible and the proteins are expressed in their natural context. In this study, we describe a method that extracts this valuable information in the form of predicted conformations, allowing the user to explore the conformational landscape, to search for structures that correlate with an activity state, and estimate the abundance of conformations in the living cell. The generator is based on a Markov Chain Monte Carlo simulation that uses the interaction dataset as input and is constrained by the physical resolution of the assay. We applied this method to an 18-member protein complex composed of the seven core proteins of the budding yeast Arp2/3 complex and 11 associated regulators and effector proteins. We generated 20,480 output structures and identified conformational states using principle component analysis. We interrogated the conformation landscape and found evidence of symmetry breaking, a mixture of likely active and inactive conformational states and dynamic exchange of the core protein Arc15 between core and regulatory components. Our method provides a novel tool for prediction and

  17. High-energy intermediates in protein unfolding characterized by thiol labeling under nativelike conditions.

    Science.gov (United States)

    Malhotra, Pooja; Udgaonkar, Jayant B

    2014-06-10

    A protein unfolding reaction usually appears to be so dominated by a large free energy barrier that identifying and characterizing high-energy intermediates and, hence, dissecting the unfolding reaction into multiple structural transitions have proven to be a challenge. In particular, it has been difficult to identify any detected high-energy intermediate with the dry (DMG) and wet (WMG) molten globules that have been implicated in the unfolding reactions of at least some proteins. In this study, a native-state thiol labeling methodology was used to identify high-energy intermediates, as well as to delineate the barriers to the disruption of side chain packing interactions and to site-specific solvent exposure in different regions of the small protein, single-chain monellin (MNEI). Labeling studies of four single-cysteine-containing variants of MNEI have identified three high-energy intermediates, populated to very low extents under nativelike conditions. A significant dispersion in the opening rates of the cysteine side chains has allowed multiple steps, leading to the loss of side chain packing, to be resolved temporally. A detailed structural analysis of the positions of the four cysteine residue positions, which are buried to different depths within the protein, has suggested a direct correlation with the structure of a DMG, detected in previous studies. It is observed that side chain packing within the core of the protein is maintained, while that at the surface is disrupted, in the DMG. The core of the protein becomes solvent-exposed only in a WMG populated after the rate-limiting step of unfolding at high denaturant concentrations.

  18. U.S. Geological Survey Science for the Wyoming Landscape Conservation Initiative: 2012 annual report

    Science.gov (United States)

    Bowen, Zachary H.; Aldridge, Cameron L.; Anderson, Patrick J.; Assal, Timothy J.; Bern, Carleton R.; Biewick, Laura; Boughton, Gregory K.; Carr, Natasha B.; Chalfoun, Anna D.; Chong, Geneva W.; Clark, Melanie L.; Fedy, Bradford C.; Foster, Katharine; Garman, Steven L.; Germaine, Stephen S.; Hethcoat, Matthew G.; Homer, Collin G.; Kauffman, Matthew J.; Keinath, Douglas; Latysh, Natalie; Manier, Daniel J.; McDougal, Robert R.; Melcher, Cynthia P.; Miller, Kirk A.; Montag, Jessica; Potter, Christopher J.; Schell, Spencer; Shafer, Sarah L.; Smith, David B.; Sweat, Michael J.; Wilson, Anna B.

    2014-01-01

    Southwest Wyoming contains abundant energy resources, wildlife, habitat, open spaces, and outdoor recreational opportunities. Although energy exploration and development have been taking place in the region since the late 1800s, the pace of development for fossil fuels and renewable energy increased significantly in the early 2000s. This and the associated urban and exurban development are leading to landscape-level environmental and socioeconomic changes that have the potential to diminish wildlife habitat and other natural resources, and the quality of human lives, in Southwest Wyoming. The potential for negative effects of these changes prompted Federal, State, and local agencies to undertake the Wyoming Landscape Conservation Initiative for Southwest Wyoming.

  19. Dark matter RNA: an intelligent scaffold for the dynamic regulation of the nuclear information landscape

    Science.gov (United States)

    St. Laurent, Georges; Savva, Yiannis A.; Kapranov, Philipp

    2012-01-01

    Perhaps no other topic in contemporary genomics has inspired such diverse viewpoints as the 95+% of the genome, previously known as “junk DNA,” that does not code for proteins. Here, we present a theory in which dark matter RNA plays a role in the generation of a landscape of spatial micro-domains coupled to the information signaling matrix of the nuclear landscape. Within and between these micro-domains, dark matter RNAs additionally function to tether RNA interacting proteins and complexes of many different types, and by doing so, allow for a higher performance of the various processes requiring them at ultra-fast rates. This improves signal to noise characteristics of RNA processing, trafficking, and epigenetic signaling, where competition and differential RNA binding among proteins drives the computational decisions inherent in regulatory events. PMID:22539933

  20. Dystropathology Increases Energy Expenditure and Protein Turnover in the Mdx Mouse Model of Duchenne Muscular Dystrophy

    Science.gov (United States)

    Radley-Crabb, Hannah G.; Marini, Juan C.; Sosa, Horacio A.; Castillo, Liliana I.; Grounds, Miranda D.; Fiorotto, Marta L.

    2014-01-01

    The skeletal muscles in Duchenne muscular dystrophy and the mdx mouse model lack functional dystrophin and undergo repeated bouts of necrosis, regeneration, and growth. These processes have a high metabolic cost. However, the consequences for whole body energy and protein metabolism, and on the dietary requirements for these macronutrients at different stages of the disease, are not well-understood. This study used juvenile (4- to 5- wk-old) and adult (12- to 14-wk-old) male dystrophic C57BL/10ScSn-mdx/J and age-matched C57BL/10ScSn/J control male mice to measure total and resting energy expenditure, food intake, spontaneous activity, body composition, whole body protein turnover, and muscle protein synthesis rates. In juvenile mdx mice that have extensive muscle damage, energy expenditure, muscle protein synthesis, and whole body protein turnover rates were higher than in age-matched controls. Adaptations in food intake and decreased activity were insufficient to meet the increased energy and protein needs of juvenile mdx mice and resulted in stunted growth. In (non-growing) adult mdx mice with less severe dystropathology, energy expenditure, muscle protein synthesis, and whole body protein turnover rates were also higher than in age-matched controls. Food intake was sufficient to meet their protein and energy needs, but insufficient to result in fat deposition. These data show that dystropathology impacts the protein and energy needs of mdx mice and that tailored dietary interventions are necessary to redress this imbalance. If not met, the resultant imbalance blunts growth, and may limit the benefits of therapies designed to protect and repair dystrophic muscles. PMID:24586653

  1. GIS-based landscape design research: Stourhead landscape garden as a case study

    Directory of Open Access Journals (Sweden)

    Steffen Nijhuis

    2017-11-01

    Full Text Available Landscape design research is important for cultivating spatial intelligence in landscape architecture. This study explores GIS (geographic information systems as a tool for landscape design research - investigating landscape designs to understand them as architectonic compositions (architectonic plan analysis. The concept ‘composition’ refers to a conceivable arrangement, an architectural expression of a mental construct that is legible and open to interpretation. Landscape architectonic compositions and their representations embody a great wealth of design knowledge as objects of our material culture and reflect the possible treatment of the ground, space, image and program as a characteristic coherence. By exploring landscape architectonic compositions with GIS, design researchers can acquire design knowledge that can be used in the creation and refinement of a design.  The research aims to identify and illustrate the potential role of GIS as a tool in landscape design research, so as to provide insight into the possibilities and limitations of using GIS in this capacity. The critical, information-oriented case of Stourhead landscape garden (Wiltshire, UK, an example of a designed landscape that covers the scope and remit of landscape architecture design, forms the heart of the study. The exploration of Stourhead by means of GIS can be understood as a plausibility probe. Here the case study is considered a form of ‘quasi-experiment’, testing the hypothesis and generating a learning process that constitutes a prerequisite for advanced understanding, while using an adjusted version of the framework for landscape design analysis by Steenbergen and Reh (2003. This is a theoretically informed analytical method based on the formal interpretation of the landscape architectonic composition addressing four landscape architectonic categories: the basic, the spatial, the symbolic and the programmatic form. This study includes new aspects to be

  2. Landscape functioning assessment using Landsat multispectral remote sensing data

    OpenAIRE

    Hesslerová, Petra

    2009-01-01

    The main aim of the dissertation thesis was to develop method, based on the use of multispectral satellite data and the theory of dissipation, allowing the analysis of landscape functioning. The theoretical basis is Prigogine's theory of dissipation and self-organization of structures in which energy dissipation is seen as the transformation of solar energy to other forms of energy. In this process the essential role play water availability and vegetation, which is able to bind solar radiatio...

  3. Industrious Landscaping

    DEFF Research Database (Denmark)

    Brichet, Nathalia Sofie; Hastrup, Frida

    2018-01-01

    This article has a twofold ambition. It offers a history of landscaping at Søby brown coal beds—a former mining site in western Denmark—and a methodological discussion of how to write such a study. Exploring this specific industrial landscape through a series of projects that have made different...... natural resources appear, we show that even what is recognized as resources shifts over time according to radically different and unpredictable agendas. This indicates that the Søby landscape is fundamentally volatile, as its resourcefulness has been seen interchangeably to shift between the brown coal...... business, inexpensive estates for practically savvy people, pasture for grazing, and recreational forest, among other things. We discuss these rifts in landscape history, motivated by what we refer to as industriousness, to show that, at sites such as Søby, both natural resources and historical...

  4. Using Landscape metrics to analyze the landscape evolution under land abandonment

    Science.gov (United States)

    Pelorosso, Raffaele; Della Chiesa, Stefano; Gobattoni, Federica; Leone, Antonio

    2010-05-01

    The human actions and the human-linked land use changes are the main responsible of the present landscapes and vegetation patterns (Antrop, 2005; Pelorosso et al., 2009). Hence, revised concept of potential natural vegetation has been developed in landscape ecology. In fact, it cannot more be considered as the optimum for a certain landscape, but only as a general indication never widely reached. In particular Ingegnoli and Pignatti (2007) introduced the concept of fittest vegetation as "the most suitable or suited vegetation for the specific climate and geomorphic conditions, in a limited period of time and in a certain defined place with a particular range of incorporable disturbances (including man's) under natural or not natural conditions". Anthropic exploitation of land and its resources to obtain goods and services (Willemen et al, 2008) can be considered therefore the main cause of landscape change as an integrant part of nature, not external. The abandon of the land by farmers or other users it is one of the more felt problems for the marginal territories of Mediterranean basin. It is therefore caused by socio-economic changes of last decades and cause several impact on biodiversity (Geri et al. 2010) and hydro-geological assessment. A mountain landscape has however the capacity to provide goods like timber and services like aesthetic pleasure or regulation of water system. The necessity of a conservation strategy and the development of sustainable socio-economic management plan play a very important role in governing land and quality of life for people and ecosystems also for marginal territory. After a land abandonment, soil conditions and several climatic and orographic characteristic plus human disturbance affect the length of time required by secondary succession, throwing the establishment of vegetation with different association, structure and composition until a (stable or meta-stable) equilibrium is reached (Ingegnoli and Pignatti, 2007). In this

  5. Branches of the landscape

    International Nuclear Information System (INIS)

    Dine, Michael; O'Neil, Deva; Sun Zheng

    2005-01-01

    With respect to the question of supersymmetry breaking, there are three branches of the flux landscape. On one of these, if one requires small cosmological constant, supersymmetry breaking is predominantly at the fundamental scale; on another, the distribution is roughly flat on a logarithmic scale; on the third, the preponderance of vacua are at very low scale. A priori, as we will explain, one can say little about the first branch. The vast majority of these states are not accessible even to crude, approximate analysis. On the other two branches one can hope to do better. But as a result of the lack of access to branch one, and our poor understanding of cosmology, we can at best conjecture about whether string theory predicts low energy supersymmetry or not. If we hypothesize that are on branch two or three, distinctive predictions may be possible. We comment of the status of naturalness within the landscape, deriving, for example, the statistics of the first branch from simple effective field theory reasoning

  6. Detectability of landscape effects on recolonization increases with regional population density.

    Science.gov (United States)

    Liman, Anna-Sara; Dalin, Peter; Björkman, Christer

    2015-07-01

    Variation in population size over time can influence our ability to identify landscape-moderated differences in community assembly. To date, however, most studies at the landscape scale only cover snapshots in time, thereby overlooking the temporal dynamics of populations and communities. In this paper, we present data that illustrate how temporal variation in population density at a regional scale can influence landscape-moderated variation in recolonization and population buildup in disturbed habitat patches. Four common insect species, two omnivores and two herbivores, were monitored over 8 years in 10 willow short-rotation coppice bio-energy stands with a four-year disturbance regime (coppice cycle). The population densities in these regularly disturbed stands were compared to densities in 17 undisturbed natural Salix cinerea (grey willow) stands in the same region. A time series approach was used, utilizing the natural variation between years to statistically model recolonization as a function of landscape composition under two different levels of regional density. Landscape composition, i.e. relative amount of forest vs. open agricultural habitats, largely determined the density of re-colonizing populations following willow coppicing in three of the four species. However, the impact of landscape composition was not detectable in years with low regional density. Our results illustrate that landscape-moderated recolonization can change over time and that considering the temporal dynamics of populations may be crucial when designing and evaluating studies at landscape level.

  7. Selecting landscape metrics as indicators of spatial heterogeneity-A comparison among Greek landscapes

    Science.gov (United States)

    Plexida, Sofia G.; Sfougaris, Athanassios I.; Ispikoudis, Ioannis P.; Papanastasis, Vasilios P.

    2014-02-01

    This paper investigates the spatial heterogeneity of three landscapes along an altitudinal gradient and different human land use. The main aim was the identification of appropriate landscape indicators using different extents. ASTER image was used to create a land cover map consisting of three landscapes which differed in altitude and land use. A number of landscape metrics quantifying patch complexity, configuration, diversity and connectivity were derived from the thematic map at the landscape level. There were significant differences among the three landscapes regarding these four aspects of landscape heterogeneity. The analysis revealed a specific pattern of land use where lowlands are being increasingly utilized by humans (percentage of agricultural land = 65.84%) characterized by physical connectedness (high values of Patch Cohesion Index) and relatively simple geometries (low values of fractal dimension index). The landscape pattern of uplands was found to be highly diverse based upon the Shannon Diversity index. After selecting the scale (600 ha) where metrics values stabilized, it was shown that metrics were more correlated at the small scale of 60 ha. From the original 24 metrics, 14 individual metrics with high Spearman correlation coefficient and Variance Inflation Factor criterion were eliminated, leaving 10 representative metrics for subsequent analysis. Data reduction analysis showed that Patch Density, Area-Weighted Mean Fractal Dimension Index and Patch Cohesion Index are suitable to describe landscape patterns irrespective of the scale. A systematic screening of these metrics could enhance a deeper understanding of the results obtained by them and contribute to a sustainable landscape management of Mediterranean landscapes.

  8. Experimental conformational energy maps of proteins and peptides.

    Science.gov (United States)

    Balaji, Govardhan A; Nagendra, H G; Balaji, Vitukudi N; Rao, Shashidhar N

    2017-06-01

    We have presented an extensive analysis of the peptide backbone dihedral angles in the PDB structures and computed experimental Ramachandran plots for their distributions seen under a various constraints on X-ray resolution, representativeness at different sequence identity percentages, and hydrogen bonding distances. These experimental distributions have been converted into isoenergy contour plots using the approach employed previously by F. M. Pohl. This has led to the identification of energetically favored minima in the Ramachandran (ϕ, ψ) plots in which global minima are predominantly observed either in the right-handed α-helical or the polyproline II regions. Further, we have identified low energy pathways for transitions between various minima in the (ϕ,ψ) plots. We have compared and presented the experimental plots with published theoretical plots obtained from both molecular mechanics and quantum mechanical approaches. In addition, we have developed and employed a root mean square deviation (RMSD) metric for isoenergy contours in various ranges, as a measure (in kcal.mol -1 ) to compare any two plots and determine the extent of correlation and similarity between their isoenergy contours. In general, we observe a greater degree of compatibility with experimental plots for energy maps obtained from molecular mechanics methods compared to most quantum mechanical methods. The experimental energy plots we have investigated could be helpful in refining protein structures obtained from X-ray, NMR, and electron microscopy and in refining force field parameters to enable simulations of peptide and protein structures that have higher degree of consistency with experiments. Proteins 2017; 85:979-1001. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Influence of feeding varying crude protein and digestible energy ...

    African Journals Online (AJOL)

    Influence of feeding varying crude protein and digestible energy levels on the development of individual muscles, rate of lean and fat deposition in pigs reared from 9 to 60kg liveweight in a humid tropical environment.

  10. Landscape Painting in Evaluation of Changes in Landscape

    Czech Academy of Sciences Publication Activity Database

    Lacina, Jan; Halas, Petr

    2015-01-01

    Roč. 8, č. 2 (2015), s. 60-68 ISSN 1803-2427 Institutional support: RVO:68145535 Keywords : landscape painting * landscape ecology * land-use changes * biodiversity Subject RIV: DE - Earth Magnetism, Geodesy, Geography http://www.degruyter.com/view/j/jlecol.2015.8.issue-2/jlecol-2015-0009/jlecol-2015-0009. xml

  11. Urban Landscape Perspectives

    Directory of Open Access Journals (Sweden)

    Frederick Steiner

    2014-03-01

    Full Text Available Cities present significant opportunities for new landscape perspectives that can help inform conservation and development decisions. Early in the twenty-first century, the majority of the planet’s population became urban as more people lived in city-regions for the first time in our history. As the global population increases, so does this urbanization. The environmental challenges of population and urban growth are profound. Landscapes represent a synthesis of natural and cultural processes. Cities are certainly cultural phenomena. Historically, cities provided refuge from nature. The expanding field of urban ecology, coupled with landscape ecology, can enhance how the dual natural and cultural dimensions of landscapes in cities are understood. Furthermore, concepts such as ecosystem services and green infrastructure are proving useful for urban landscape planning and design. Examples from Dayton, Ohio; Brooklyn, New York; and Austin, Texas are presented.

  12. Dietary protein content alters energy expenditure and composition of the mass gain in grizzly bears (Ursus arctos horribilis).

    Science.gov (United States)

    Felicetti, Laura A; Robbins, Charles T; Shipley, Lisa A

    2003-01-01

    Many fruits contain high levels of available energy but very low levels of protein and other nutrients. The discrepancy between available energy and protein creates a physiological paradox for many animals consuming high-fruit diets, as they will be protein deficient if they eat to meet their minimum energy requirement. We fed young grizzly bears both high-energy pelleted and fruit diets containing from 1.6% to 15.4% protein to examine the role of diet-induced thermogenesis and fat synthesis in dealing with high-energy-low-protein diets. Digestible energy intake at mass maintenance increased 2.1 times, and composition of the gain changed from primarily lean mass to entirely fat when the protein content of the diet decreased from 15.4% to 1.6%. Daily fat gain was up to three times higher in bears fed low-protein diets ad lib., compared with bears consuming the higher-protein diet and gaining mass at the same rate. Thus, bears eating fruit can either consume other foods to increase dietary protein content and reduce energy expenditure, intake, and potentially foraging time or overeat high-fruit diets and use diet-induced thermogenesis and fat synthesis to deal with their skewed energy-to-protein ratio. These are not discrete options but a continuum that creates numerous solutions for balancing energy expenditure, intake, foraging time, fat accumulation, and ultimately fitness, depending on food availability, foraging efficiency, bear size, and body condition.

  13. Molecular modeling of the conformational dynamics of the cellular prion protein

    Science.gov (United States)

    Nguyen, Charles; Colling, Ian; Bartz, Jason; Soto, Patricia

    2014-03-01

    Prions are infectious agents responsible for transmissible spongiform encephalopathies (TSEs), a type of fatal neurodegenerative disease in mammals. Prions propagate biological information by conversion of the non-pathological version of the prion protein to the infectious conformation, PrPSc. A wealth of knowledge has shed light on the nature and mechanism of prion protein conversion. In spite of the significance of this problem, we are far from fully understanding the conformational dynamics of the cellular isoform. To remedy this situation we employ multiple biomolecular modeling techniques such as docking and molecular dynamics simulations to map the free energy landscape and determine what specific regions of the prion protein are most conductive to binding. The overall goal is to characterize the conformational dynamics of the cell form of the prion protein, PrPc, to gain insight into inhibition pathways against misfolding. NE EPSCoR FIRST Award to Patricia Soto.

  14. Overcoming potential energy distortions in constrained internal coordinate molecular dynamics simulations

    Energy Technology Data Exchange (ETDEWEB)

    Kandel, Saugat; Salomon-Ferrer, Romelia; Larsen, Adrien B.; Vaidehi, Nagarajan, E-mail: nvaidehi@coh.org [Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010 (United States); Jain, Abhinandan, E-mail: Abhi.Jain@jpl.nasa.gov [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, California 91109 (United States)

    2016-01-28

    The Internal Coordinate Molecular Dynamics (ICMD) method is an attractive molecular dynamics (MD) method for studying the dynamics of bonded systems such as proteins and polymers. It offers a simple venue for coarsening the dynamics model of a system at multiple hierarchical levels. For example, large scale protein dynamics can be studied using torsional dynamics, where large domains or helical structures can be treated as rigid bodies and the loops connecting them as flexible torsions. ICMD with such a dynamic model of the protein, combined with enhanced conformational sampling method such as temperature replica exchange, allows the sampling of large scale domain motion involving high energy barrier transitions. Once these large scale conformational transitions are sampled, all-torsion, or even all-atom, MD simulations can be carried out for the low energy conformations sampled via coarse grained ICMD to calculate the energetics of distinct conformations. Such hierarchical MD simulations can be carried out with standard all-atom forcefields without the need for compromising on the accuracy of the forces. Using constraints to treat bond lengths and bond angles as rigid can, however, distort the potential energy landscape of the system and reduce the number of dihedral transitions as well as conformational sampling. We present here a two-part solution to overcome such distortions of the potential energy landscape with ICMD models. To alleviate the intrinsic distortion that stems from the reduced phase space in torsional MD, we use the Fixman compensating potential. To additionally alleviate the extrinsic distortion that arises from the coupling between the dihedral angles and bond angles within a force field, we propose a hybrid ICMD method that allows the selective relaxing of bond angles. This hybrid ICMD method bridges the gap between all-atom MD and torsional MD. We demonstrate with examples that these methods together offer a solution to eliminate the potential

  15. Landscape encodings enhance optimization.

    Directory of Open Access Journals (Sweden)

    Konstantin Klemm

    Full Text Available Hard combinatorial optimization problems deal with the search for the minimum cost solutions (ground states of discrete systems under strong constraints. A transformation of state variables may enhance computational tractability. It has been argued that these state encodings are to be chosen invertible to retain the original size of the state space. Here we show how redundant non-invertible encodings enhance optimization by enriching the density of low-energy states. In addition, smooth landscapes may be established on encoded state spaces to guide local search dynamics towards the ground state.

  16. Landscape Encodings Enhance Optimization

    Science.gov (United States)

    Klemm, Konstantin; Mehta, Anita; Stadler, Peter F.

    2012-01-01

    Hard combinatorial optimization problems deal with the search for the minimum cost solutions (ground states) of discrete systems under strong constraints. A transformation of state variables may enhance computational tractability. It has been argued that these state encodings are to be chosen invertible to retain the original size of the state space. Here we show how redundant non-invertible encodings enhance optimization by enriching the density of low-energy states. In addition, smooth landscapes may be established on encoded state spaces to guide local search dynamics towards the ground state. PMID:22496860

  17. Incorporating Bioenergy in Sustainable Landscape Designs Workshop Two: Agricultural Landscapes

    Energy Technology Data Exchange (ETDEWEB)

    None

    2015-08-01

    The Bioenergy Technologies Office hosted two workshops on Incorporating Bioenergy in Sustainable Landscape Designs with Oak Ridge and Argonne National Laboratories in 2014. The second workshop focused on agricultural landscapes and took place in Argonne, IL from June 24—26, 2014. The workshop brought together experts to discuss how landscape design can contribute to the deployment and assessment of sustainable bioenergy. This report summarizes the discussions that occurred at this particular workshop.

  18. Free-Energy Landscape of Reverse tRNA Translocation through the Ribosome Analyzed by Electron Microscopy Density Maps and Molecular Dynamics Simulations

    Science.gov (United States)

    Ishida, Hisashi; Matsumoto, Atsushi

    2014-01-01

    To understand the mechanism of reverse tRNA translocation in the ribosome, all-atom molecular dynamics simulations of the ribosome-tRNAs-mRNA-EFG complex were performed. The complex at the post-translocational state was directed towards the translocational and pre-translocational states by fitting the complex into cryo-EM density maps. Between a series of the fitting simulations, umbrella sampling simulations were performed to obtain the free-energy landscape. Multistep structural changes, such as a ratchet-like motion and rotation of the head of the small subunit were observed. The free-energy landscape showed that there were two main free-energy barriers: one between the post-translocational and intermediate states, and the other between the pre-translocational and intermediate states. The former corresponded to a clockwise rotation, which was coupled to the movement of P-tRNA over the P/E-gate made of G1338, A1339 and A790 in the small subunit. The latter corresponded to an anticlockwise rotation of the head, which was coupled to the location of the two tRNAs in the hybrid state. This indicates that the coupled motion of the head rotation and tRNA translocation plays an important role in opening and closing of the P/E-gate during the ratchet-like movement in the ribosome. Conformational change of EF-G was interpreted to be the result of the combination of the external motion by L12 around an axis passing near the sarcin-ricin loop, and internal hinge-bending motion. These motions contributed to the movement of domain IV of EF-G to maintain its interaction with A/P-tRNA. PMID:24999999

  19. Free-energy landscape of reverse tRNA translocation through the ribosome analyzed by electron microscopy density maps and molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Hisashi Ishida

    Full Text Available To understand the mechanism of reverse tRNA translocation in the ribosome, all-atom molecular dynamics simulations of the ribosome-tRNAs-mRNA-EFG complex were performed. The complex at the post-translocational state was directed towards the translocational and pre-translocational states by fitting the complex into cryo-EM density maps. Between a series of the fitting simulations, umbrella sampling simulations were performed to obtain the free-energy landscape. Multistep structural changes, such as a ratchet-like motion and rotation of the head of the small subunit were observed. The free-energy landscape showed that there were two main free-energy barriers: one between the post-translocational and intermediate states, and the other between the pre-translocational and intermediate states. The former corresponded to a clockwise rotation, which was coupled to the movement of P-tRNA over the P/E-gate made of G1338, A1339 and A790 in the small subunit. The latter corresponded to an anticlockwise rotation of the head, which was coupled to the location of the two tRNAs in the hybrid state. This indicates that the coupled motion of the head rotation and tRNA translocation plays an important role in opening and closing of the P/E-gate during the ratchet-like movement in the ribosome. Conformational change of EF-G was interpreted to be the result of the combination of the external motion by L12 around an axis passing near the sarcin-ricin loop, and internal hinge-bending motion. These motions contributed to the movement of domain IV of EF-G to maintain its interaction with A/P-tRNA.

  20. How wind power landscapes change

    DEFF Research Database (Denmark)

    Möller, Bernd

    2006-01-01

    Following 25 years of continuous development, Danish wind energy landscapes are going to face changes. Ceased on-shore construction, unresolved re-powering and stalled regional planning characterize the situation overshadowed by off-shore development. One of the factors inhibiting development...... in general. However, the pattern of visibility will become askew, and the present homogenous distribution of visibility will disappear. This skewness, together with changing ownership and receding local involvement, could eventually lead to lower popular acceptance of wind power....

  1. Influence of energy concentration and source on the utilization of feed protein and NPN in lambs. 3. Allantoin excretion and microbial protein synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Ulbrich, M; Geissler, C; Bassuny, S M; Borowiec, F; Hoffmann, M

    1989-06-01

    In an N balance experiment with male crossbreeding lambs at an age of 3-4 months four different rations were given differing in energy concentration (high > 700 EFU/sub cattle//kg DM and low < 650 EFU/sub cattle//kg DM) and in the energy source (sugar, starch or crude fibre) with crude protein intake being almost equal. The rations contained 2% urea. Microbial protein synthesis in the rumen was assessed according to Roth and Kichgessner (1978) (1), Rys et al. (1975) (2) and Bickel-Baumann and Landis (1986) (3) on the basis of allantoin excretion in urine. The highest ruminal protein synthesis quotas were 868-921 mg protein N per kg LW/sup 0.75/ in (2). In (3) 723-766 mg protein N/kg LW /sup 0.75/ were synthesized. From the /sup 15/N labelling of the supplemented urea and the excreted allantoin it could be calculated that 26-40% of the microbial protein resulted from the urea-N of the ration. Despite a high crude protein content of the ration of between 16 and 17% in the DM and a relation of NPN: pure protein of 0.95 the utilization of the NPN in the ration was relatively high but slightly lower than the utilization of pure protein. The variants with higher energy concentration showed as a tendency higher allantoin excretion in spite of slightly lower dry matter intake and a slightly higher NPN utilization than the variants with lower energy concentration. (author).

  2. Whey protein consumption after resistance exercise reduces energy intake at a post-exercise meal.

    Science.gov (United States)

    Monteyne, Alistair; Martin, Alex; Jackson, Liam; Corrigan, Nick; Stringer, Ellen; Newey, Jack; Rumbold, Penny L S; Stevenson, Emma J; James, Lewis J

    2018-03-01

    Protein consumption after resistance exercise potentiates muscle protein synthesis, but its effects on subsequent appetite in this context are unknown. This study examined appetite and energy intake following consumption of protein- and carbohydrate-containing drinks after resistance exercise. After familiarisation, 15 resistance training males (age 21 ± 1 years, body mass 78.0 ± 11.9 kg, stature 1.78 ± 0.07 m) completed two randomised, double-blind trials, consisting of lower-body resistance exercise, followed by consumption of a whey protein (PRO 23.9 ± 3.6 g protein) or dextrose (CHO 26.5 ± 3.8 g carbohydrate) drink in the 5 min post-exercise. An ad libitum meal was served 60 min later, with subjective appetite measured throughout. Drinks were flavoured and matched for energy content and volume. The PRO drink provided 0.3 g/kg body mass protein. Ad libitum energy intake (PRO 3742 ± 994 kJ; CHO 4172 ± 1132 kJ; P = 0.007) and mean eating rate (PRO 339 ± 102 kJ/min; CHO 405 ± 154 kJ/min; P = 0.009) were lower during PRO. The change in eating rate was associated with the change in energy intake (R = 0.661, P = 0.007). No interaction effects were observed for subjective measures of appetite. The PRO drink was perceived as creamier and thicker, and less pleasant, sweet and refreshing (P consumption after resistance exercise reduces subsequent energy intake, and this might be partially mediated by a reduced eating rate. Whilst this reduced energy intake is unlikely to impair hypertrophy, it may be of value in supporting an energy deficit for weight loss.

  3. Probing intermolecular protein-protein interactions in the calcium-sensing receptor homodimer using bioluminescence resonance energy transfer (BRET)

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Hansen, Jakob L; Sheikh, Søren P

    2002-01-01

    -induced intermolecular movements in the CaR homodimer using the new bioluminescence resonance energy transfer technique, BRET2, which is based on the transference of energy from Renilla luciferase (Rluc) to the green fluorescent protein mutant GFP2. We tagged CaR with Rluc and GFP2 at different intracellular locations...

  4. Landscape Evolution Modelling-LAPSUS

    Energy Technology Data Exchange (ETDEWEB)

    Baartman, J. E. M.; Temme, A. J. A. M.; Schoorl, J. M.; Claessens, L.; Viveen, W.; Gorp, W. van; Veldkamp, A.

    2009-07-01

    Landscape evolution modelling can make the consequences of landscape evolution hypotheses explicit and theoretically allows for their falsification and improvement. ideally, landscape evolution models (LEMs) combine the results of all relevant landscape forming processes into an ever-adapting digital landscape (e.g. DEM). These processes may act on different spatial and temporal scales. LAPSUS is such a LEM. Processes that have in different studies been included in LAPSUS are water erosion and deposition, landslide activity, creep, solidification, weathering, tectonics and tillage. Process descriptions are as simple and generic as possible, ensuring wide applicability. (Author) 25 refs.

  5. Landscape Evolution Modelling-LAPSUS

    International Nuclear Information System (INIS)

    Baartman, J. E. M.; Temme, A. J. A. M.; Schoorl, J. M.; Claessens, L.; Viveen, W.; Gorp, W. van; Veldkamp, A.

    2009-01-01

    Landscape evolution modelling can make the consequences of landscape evolution hypotheses explicit and theoretically allows for their falsification and improvement. ideally, landscape evolution models (LEMs) combine the results of all relevant landscape forming processes into an ever-adapting digital landscape (e.g. DEM). These processes may act on different spatial and temporal scales. LAPSUS is such a LEM. Processes that have in different studies been included in LAPSUS are water erosion and deposition, landslide activity, creep, solidification, weathering, tectonics and tillage. Process descriptions are as simple and generic as possible, ensuring wide applicability. (Author) 25 refs.

  6. Navigating the Interface Between Landscape Genetics and Landscape Genomics

    Directory of Open Access Journals (Sweden)

    Andrew Storfer

    2018-03-01

    Full Text Available As next-generation sequencing data become increasingly available for non-model organisms, a shift has occurred in the focus of studies of the geographic distribution of genetic variation. Whereas landscape genetics studies primarily focus on testing the effects of landscape variables on gene flow and genetic population structure, landscape genomics studies focus on detecting candidate genes under selection that indicate possible local adaptation. Navigating the transition between landscape genomics and landscape genetics can be challenging. The number of molecular markers analyzed has shifted from what used to be a few dozen loci to thousands of loci and even full genomes. Although genome scale data can be separated into sets of neutral loci for analyses of gene flow and population structure and putative loci under selection for inference of local adaptation, there are inherent differences in the questions that are addressed in the two study frameworks. We discuss these differences and their implications for study design, marker choice and downstream analysis methods. Similar to the rapid proliferation of analysis methods in the early development of landscape genetics, new analytical methods for detection of selection in landscape genomics studies are burgeoning. We focus on genome scan methods for detection of selection, and in particular, outlier differentiation methods and genetic-environment association tests because they are the most widely used. Use of genome scan methods requires an understanding of the potential mismatches between the biology of a species and assumptions inherent in analytical methods used, which can lead to high false positive rates of detected loci under selection. Key to choosing appropriate genome scan methods is an understanding of the underlying demographic structure of study populations, and such data can be obtained using neutral loci from the generated genome-wide data or prior knowledge of a species

  7. Linear growth of children on a ketogenic diet: does the protein-to-energy ratio matter?

    Science.gov (United States)

    Nation, Judy; Humphrey, Maureen; MacKay, Mark; Boneh, Avihu

    2014-11-01

    Ketogenic diet is a structured effective treatment for children with intractable epilepsy. Several reports have indicated poor linear growth in children on the diet but the mechanism of poor growth has not been elucidated. We aimed to explore whether the protein to energy ratio plays a role in linear growth of children on ketogenic diet. Data regarding growth and nutrition were, retrospectively, collected from the clinical histories of 35 children who were treated with ketogenic diet for at least 6 months between 2002 and 2010. Patients were stratified into groups according to periods of satisfactory or poor linear growth. Poor linear growth was associated with protein or caloric intake of <80% recommended daily intake, and with a protein-to-energy ratio consistently ≤1.4 g protein/100 kcal even when protein and caloric intakes were adequate. We recommend a protein-to-energy ratio of 1.5 g protein/100 kcal be prescribed to prevent growth retardation. © The Author(s) 2013.

  8. URBAN LANDSCAPE QUALITY AND FACTORS THAT HAVE INFLUENCE ON LANDSCAPE QUALITY IN LATGALE REGION

    OpenAIRE

    Matisovs, Ivars

    2005-01-01

    The paper deals with urban landscape individualities in the cities and towns of Latgale region. Also show facilities and methods of integrated assessment of urban landscape quality. Article provides information about specifics of urban landscape and factors, that have influence on landscape quality. The paper presents the results of Daugavpils and Rēzekne urban landscape quality complex assessment, that have been realised in 2003- 2005. This results don’t establish significant disparities bet...

  9. Effects of protein and energy deficiency on the incorporation of 14C-Chlorella protein hydrolysate into body constituents of adult rats

    International Nuclear Information System (INIS)

    Yamamoto, Shigeru; Wakabayashi, Kazuo; Niiyama, Yoshiaki; Inoue, Goro

    1974-01-01

    The effects of protein and/or energy deficiency on 14 C incorporation into body constituents and 14 C output in expired air and urine were investigated in adult rats using 14 C-Chlorella protein hydrolysate. Rats were given a protein-free diet (PFD) for 2 weeks and conrol rats were fed ad libitum or pari-fed with the PFD group on a 12% lactalbumin diet (LA and Pair-fed, respectively). On the 15th day, animals received 14 C-Chlorella protein hydolysate with 5 g of their respective diet. One group of PFD animals was given tracer by stomach tube without food (PFD-fast). Normal control rats ate about twice as much diet as the PFD group. The respiratory 14 C output in the PFD group was identical with those in the LA and Pair-fed groups and was less than that in the PFD-fast group. The rate of protein synthesis, provisionally expressed as relative specific radioactivity, was more in the PFD group than in the normal group in the liver and less than the latter in the muscle. The LA group retained less total radioactivity in the body than the Pair-fed or PFD group, indicating high capability to hold the body protein in protein deficiency. In addition, decreased conversion of amino acids to lipids and glycogen was observed in the PFD group. All these differences are interpreted as adaptations to protein shortage. On prolonged fasting (PFD-fast group), gluconeogenesis in the liver increased to provide energy, despite the protein deficiency. The relative importances of protein and energy for tissue protein synthesis are briefly discussed. (author)

  10. Reverse triiodothyronine in protein energy malnutrition

    International Nuclear Information System (INIS)

    Hafiez, A.A.; Abdel-Salam, E.; Abbas, E.Z.; Halawa, F.A.; El-Hefnawy, N.

    1984-01-01

    Serum levels of thyroxine (T 4 ), triiodothyronine (T 3 ), reverse triiodothyronine (rT 3 ) and thyrotropin (TSH) were determined in cases of kwashiorkor and marasmus. Decreased levels of T 4 and T 3 , and increased levels of rT 3 with no change in TSH were obtained. Thus in infants suffering from protein energy malnutrition there is a state of thyroid dysfunction as well as a shift in the peripheral T 4 metabolism being converted to the inert rT 3 rather than to the physiologically active T 3 . (author)

  11. Protein energy malnutrition decreases immunity and increases susceptibility to influenza infection in mice.

    Science.gov (United States)

    Taylor, Andrew K; Cao, Weiping; Vora, Keyur P; De La Cruz, Juan; Shieh, Wun-Ju; Zaki, Sherif R; Katz, Jacqueline M; Sambhara, Suryaprakash; Gangappa, Shivaprakash

    2013-02-01

    Protein energy malnutrition (PEM), a common cause of secondary immune deficiency in children, is associated with an increased risk of infections. Very few studies have addressed the relevance of PEM as a risk factor for influenza. We investigated the influence of PEM on susceptibility to, and immune responses following, influenza virus infection using isocaloric diets providing either adequate protein (AP; 18%) or very low protein (VLP; 2%) in a mouse model. We found that mice maintained on the VLP diet, when compared to mice fed with the AP diet, exhibited more severe disease following influenza infection based on virus persistence, trafficking of inflammatory cell types to the lung tissue, and virus-induced mortality. Furthermore, groups of mice maintained on the VLP diet showed significantly lower virus-specific antibody response and a reduction in influenza nuclear protein-specific CD8(+) T cells compared with mice fed on the AP diet. Importantly, switching diets for the group maintained on the VLP diet to the AP diet improved virus clearance, as well as protective immunity to viral challenge. Our results highlight the impact of protein energy on immunity to influenza infection and suggest that balanced protein energy replenishment may be one strategy to boost immunity against influenza viral infections.

  12. Prediction of the optimal set of contacts to fold the smallest knotted protein

    International Nuclear Information System (INIS)

    Dabrowski-Tumanski, P; Jarmolinska, A I; Sulkowska, J I

    2015-01-01

    Knotted protein chains represent a new motif in protein folds. They have been linked to various diseases, and recent extensive analysis of the Protein Data Bank shows that they constitute 1.5% of all deposited protein structures. Despite thorough theoretical and experimental investigations, the role of knots in proteins still remains elusive. Nonetheless, it is believed that knots play an important role in mechanical and thermal stability of proteins. Here, we perform a comprehensive analysis of native, shadow-specific and non-native interactions which describe free energy landscape of the smallest knotted protein (PDB id 2efv). We show that the addition of shadow-specific contacts in the loop region greatly enhances folding kinetics, while the addition of shadow-specific contacts along the C-terminal region (H3 or H4) results in a new folding route with slower kinetics. By means of direct coupling analysis (DCA) we predict non-native contacts which also can accelerate kinetics. Next, we show that the length of the C-terminal knot tail is responsible for the shape of the free energy barrier, while the influence of the elongation of the N-terminus is not significant. Finally, we develop a concept of a minimal contact map sufficient for 2efv protein to fold and analyze properties of this protein using this map. (paper)

  13. Prediction of the optimal set of contacts to fold the smallest knotted protein

    Science.gov (United States)

    Dabrowski-Tumanski, P.; Jarmolinska, A. I.; Sulkowska, J. I.

    2015-09-01

    Knotted protein chains represent a new motif in protein folds. They have been linked to various diseases, and recent extensive analysis of the Protein Data Bank shows that they constitute 1.5% of all deposited protein structures. Despite thorough theoretical and experimental investigations, the role of knots in proteins still remains elusive. Nonetheless, it is believed that knots play an important role in mechanical and thermal stability of proteins. Here, we perform a comprehensive analysis of native, shadow-specific and non-native interactions which describe free energy landscape of the smallest knotted protein (PDB id 2efv). We show that the addition of shadow-specific contacts in the loop region greatly enhances folding kinetics, while the addition of shadow-specific contacts along the C-terminal region (H3 or H4) results in a new folding route with slower kinetics. By means of direct coupling analysis (DCA) we predict non-native contacts which also can accelerate kinetics. Next, we show that the length of the C-terminal knot tail is responsible for the shape of the free energy barrier, while the influence of the elongation of the N-terminus is not significant. Finally, we develop a concept of a minimal contact map sufficient for 2efv protein to fold and analyze properties of this protein using this map.

  14. Lines of landscape organisation

    DEFF Research Database (Denmark)

    Løvschal, Mette

    2015-01-01

    This paper offers a landscape analysis of the earliest linear landscape boundaries on Skovbjerg Moraine, Denmark, during the first millennium BC. Using Delaunay triangulation as well as classic distribution analyses, it demonstrates that landscape boundaries articulated already established use-pa...

  15. Maintenance of energy expenditure on high-protein vs. high-carbohydrate diets at a constant body weight may prevent a positive energy balance.

    Science.gov (United States)

    Martens, E A; Gonnissen, H K; Gatta-Cherifi, B; Janssens, P L; Westerterp-Plantenga, M S

    2015-10-01

    Relatively high-protein diets are effective for body weight loss, and subsequent weight maintenance, yet it remains to be shown whether these diets would prevent a positive energy balance. Therefore, high-protein diet studies at a constant body weight are necessary. The objective was to determine fullness, energy expenditure, and macronutrient balances on a high-protein low-carbohydrate (HPLC) diet compared with a high-carbohydrate low-protein (HCLP) diet at a constant body weight, and to assess whether effects are transient or sustained after 12 weeks. A randomized parallel study was performed in 14 men and 18 women [mean ± SD age: 24 ± 5 y; BMI (in kg/m(2)): 22.8 ± 2.0] on diets containing 30/35/35 (HPLC) or 5/60/35 (HCLP) % of energy from protein/carbohydrate/fat. Significant interactions between dietary intervention and time on total energy expenditure (TEE) (P = 0.013), sleeping metabolic rate (SMR) (P = 0.040), and diet-induced thermogenesis (DIT) (P = 0.027) appeared from baseline to wk 12. TEE was maintained in the HPLC diet group, while it significantly decreased throughout the intervention period in the HCLP diet group (wk 1: P = 0.002; wk 12: P = 0.001). Energy balance was maintained in the HPLC diet group, and became positive in the HCLP diet group at wk 12 (P = 0.008). Protein balance varied directly according to the amount of protein in the diet, and diverged significantly between the diets (P = 0.001). Fullness ratings were significantly higher in the HPLC vs. the HCLP diet group at wk 1 (P = 0.034), but not at wk 12. Maintenance of energy expenditure on HPLC vs. HCLP diets at a constant body weight may prevent development of a positive energy balance, despite transiently higher fullness. The study was registered on clinicaltrials.gov with Identifier: NCT01551238. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  16. Using graph approach for managing connectivity in integrative landscape modelling

    Science.gov (United States)

    Rabotin, Michael; Fabre, Jean-Christophe; Libres, Aline; Lagacherie, Philippe; Crevoisier, David; Moussa, Roger

    2013-04-01

    In cultivated landscapes, a lot of landscape elements such as field boundaries, ditches or banks strongly impact water flows, mass and energy fluxes. At the watershed scale, these impacts are strongly conditionned by the connectivity of these landscape elements. An accurate representation of these elements and of their complex spatial arrangements is therefore of great importance for modelling and predicting these impacts.We developped in the framework of the OpenFLUID platform (Software Environment for Modelling Fluxes in Landscapes) a digital landscape representation that takes into account the spatial variabilities and connectivities of diverse landscape elements through the application of the graph theory concepts. The proposed landscape representation consider spatial units connected together to represent the flux exchanges or any other information exchanges. Each spatial unit of the landscape is represented as a node of a graph and relations between units as graph connections. The connections are of two types - parent-child connection and up/downstream connection - which allows OpenFLUID to handle hierarchical graphs. Connections can also carry informations and graph evolution during simulation is possible (connections or elements modifications). This graph approach allows a better genericity on landscape representation, a management of complex connections and facilitate development of new landscape representation algorithms. Graph management is fully operational in OpenFLUID for developers or modelers ; and several graph tools are available such as graph traversal algorithms or graph displays. Graph representation can be managed i) manually by the user (for example in simple catchments) through XML-based files in easily editable and readable format or ii) by using methods of the OpenFLUID-landr library which is an OpenFLUID library relying on common open-source spatial libraries (ogr vector, geos topologic vector and gdal raster libraries). Open

  17. Modeling long-term changes in forested landscapes and their relation to the Earth's energy balance

    Science.gov (United States)

    Shugart, H. H.; Emanuel, W. R.; Solomon, A. M.

    1984-01-01

    The dynamics of the forested parts of the Earth's surface on time scales from decades to centuries are discussed. A set of computer models developed at Oak Ridge National Laboratory and elsewhere are applied as tools. These models simulate a landscape by duplicating the dynamics of growth, death and birth of each tree living on a 0.10 ha element of the landscape. This spatial unit is generally referred to as a gap in the case of the forest models. The models were tested against and applied to a diverse array of forests and appear to provide a reasonable representation for investigating forest-cover dynamics. Because of the climate linkage, one important test is the reconstruction of paleo-landscapes. Detailed reconstructions of changes in vegetation in response to changes in climate are crucial to understanding the association of the Earth's vegetation and climate and the response of the vegetation to climate change.

  18. A PM7 dynamic residue-ligand interactions energy landscape of the BACE1 inhibitory pathway by hydroxyethylamine compounds. Part I: The flap closure process.

    Science.gov (United States)

    Gueto-Tettay, Carlos; Martinez-Consuegra, Alejandro; Zuchniarz, Joshua; Gueto-Tettay, Luis Roberto; Drosos-Ramírez, Juan Carlos

    2017-09-01

    BACE1 is an enzyme of scientific interest because it participates in the progression of Alzheimer's disease. Hydroxyethylamines (HEAs) are a family of compounds which exhibit inhibitory activity toward BACE1 at a nanomolar level, favorable pharmacokinetic properties and oral bioavailability. The first step in the inhibition of BACE1 by HEAs consists of their entrance into the protease active site and the resultant conformational change in the protein, from Apo to closed form. These two conformations differ in the position of an antiparallel loop (called the flap) which covers the entrance to the catalytic site. For BACE1, closure of this flap is vital to its catalytic activity and to inhibition of the enzyme due to the new interactions thereby formed with the ligand. In the present study a dynamic energy landscape of residue-ligand interaction energies (ReLIE) measured for 112 amino acids in the BACE1 active site and its immediate vicinity during the closure of the flap induced by 8 HEAs of different inhibitory power is presented. A total of 6.272 million ReLIE calculations, based on the PM7 semiempirical method, provided a deep and quantitative view of the first step in the inhibition of the aspartyl protease. The information suggests that residues Asp93, Asp289, Thr292, Thr293, Asn294 and Arg296 are anchor points for the ligand, accounting for approximately 45% of the total protein-ligand interaction. Additionally, flap closure improved the BACE1-HEA interaction by around 25%. Furthermore, the inhibitory activity of HEAs could be related to the capacity of these ligands to form said anchor point interactions and maintain them over time: the lack of some of these anchor interactions delayed flap closure or impeded it completely, or even caused the flap to reopen. The methodology employed here could be used as a tool to evaluate future structural modifications which lead to improvements in the favorability and stability of BACE1-HEA ReLIEs, aiding in the design of

  19. Beyond the conventional: meeting the challenges of landscape governance within the European Landscape Convention?

    Science.gov (United States)

    Scott, Alister

    2011-10-01

    Academics and policy makers seeking to deconstruct landscape face major challenges conceptually, methodologically and institutionally. The meaning(s), identity(ies) and management of landscape are controversial and contested. The European Landscape Convention provides an opportunity for action and change set within new governance agendas addressing interdisciplinarity and spatial planning. This paper critically reviews the complex web of conceptual and methodological frameworks that characterise landscape planning and management and then focuses on emerging landscape governance in Scotland within a mixed method approach involving policy analyses, semi-structured interviews and best practice case studies. Using Dower's (2008) criteria from the Articles of the European Landscape Convention, the results show that whilst some progress has been made in landscape policy and practice, largely through the actions of key individuals and champions, there are significant institutional hurdles and resource limitations to overcome. The need to mainstream positive landscape outcomes requires a significant culture change where a one-size-fits-all approach does not work. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Effect of dietary protein to energy ratio on growth and nitrogenous ...

    African Journals Online (AJOL)

    The effect of dietary protein to energy ratio (P:E) on the growth of dusky kob Argyrosomus japonicus was investigated as a first step towards formulating a practical diet for this potential mariculture species in South Africa. The effects of dietary protein and lipid on growth, feed conversion ratio (FCR) and nitrogenous waste ...

  1. Evaluation of energy status of dairy cows using milk fat, protein and urea concentrations

    Directory of Open Access Journals (Sweden)

    Kirovski Danijela

    2011-11-01

    Full Text Available Energy status of dairy cows may be estimated using results for concentrations of fat, protein and urea (MUN in milk samples obtained from bulk tank or individual cows. Using individual cow milk samples is recommended on dairy farms in our geografical region due to the unhomogenity of cows in the herds in respect to their genetic potential for milk production. Depression of milk fat occurs as a consequence of heat stress, underfeeding of peripartal cows, overfeeding concentrate with reduced ration fiber levels or overfeeding with dietary fat. High milk fat content is usually combined with severe negative energy balance. Nutrition and feeding practices have great impact on milk protein level. A deficiency of crude protein in the ration may depress protein in milk. Feeding excessive dietary protein does not significantly increase milk protein. MUN analyses point out potential problems in feeding program on dairy farm. High MUN values may reflect excessive dietary crude protein and/or low rumen degradable non fiber carbohydrates intake. Also, MUN levels is impacted by heat stress since its value is increased during the summer season. Low MUNs indicate a possible dietary protein deficiency. Additionally, low MUNs concentration may indicate excess in dietary nonstructural carbohydrates. On the bases on the interrelationships between protein and urea concentrations, as well as protein and fat concentrations in individual milk sample, estimation of energy balance of dairy cows may be done more accurately.

  2. Why Landscape Beauty Matters

    Directory of Open Access Journals (Sweden)

    Angelika Krebs

    2014-11-01

    Full Text Available This philosophical paper explores the aesthetic argument for landscape conservation. The main claim is that the experience of beautiful landscapes is an essential part of the good human life. Beautiful landscapes make us feel at home in the world. Their great and irreplaceable value lies therein. To establish this claim, the concepts of landscape and “Stimmung” are clarified. It is shown how “Stimmung” (in the sense of mood is infused into landscape (as atmosphere and how we respond to it aesthetically. We respond by resonating or feeling at home. The paper ends by indicating how art can help us to better appreciate landscape beauty. This is done by way of an example from contemporary nature poetry, Michael Donhauser’s Variationen in Prosa, which begins with “Und was da war, es nahm uns an” (“And what was there accepted us”.

  3. Legible landscapes: the use of narratives in landscape design for leisure and tourism in Dutch cultural landscapes.

    NARCIS (Netherlands)

    Brinkhuijsen, M.

    2007-01-01

    Nowadays, leisure and tourism have become significant factors in rural development, which is manifest in the ‘commodification’ of landscapes. However, leisure and tourist markets are very competitive and consumers increasingly demand high quality, unique and memorable experiences. Landscape

  4. Identification Of Minangkabau Landscape Characters

    Science.gov (United States)

    Asrina, M.; Gunawan, A.; Aris, Munandar

    2017-10-01

    Minangkabau is one of cultures in indonesia which occupies landscape intact. Landscape of Minangkabau have a very close relationship with the culture of the people. Uniqueness of Minangkabau culture and landscape forming an inseparable characterunity. The landscape is necessarily identified to know the inherent landscape characters. The objective of this study was to identify the character of the Minangkabau landscape characterizes its uniqueness. The study was conducted by using descriptive method comprised literature review and field observasion. Observed the landscape characters comprised two main features, they were major and minor features. Indetification of the features was conducted in two original areas (darek) of the Minangkabau traditional society. The research results showed that major features or natural features of the landscape were predominantly landform, landcover, and hidrology. All luhak (districts) of Minangkabau showed similar main features such as hill, canyon, lake, valley, and forest. The existence of natural features such as hills, canyon and valleys characterizes the nature of minangkabau landscape. Minor features formed by Minangkabau cultural society were agricultural land and settlement. Rumah gadang (big house) is one of famous minor features characterizes the Minangkabau culture. In addition, several historical artefacts of building and others structure may strengthen uniqueness of the Minangkabau landscape character, such as The royal palace, inscription, and tunnels.

  5. Markov dynamic models for long-timescale protein motion.

    KAUST Repository

    Chiang, Tsung-Han

    2010-06-01

    Molecular dynamics (MD) simulation is a well-established method for studying protein motion at the atomic scale. However, it is computationally intensive and generates massive amounts of data. One way of addressing the dual challenges of computation efficiency and data analysis is to construct simplified models of long-timescale protein motion from MD simulation data. In this direction, we propose to use Markov models with hidden states, in which the Markovian states represent potentially overlapping probabilistic distributions over protein conformations. We also propose a principled criterion for evaluating the quality of a model by its ability to predict long-timescale protein motions. Our method was tested on 2D synthetic energy landscapes and two extensively studied peptides, alanine dipeptide and the villin headpiece subdomain (HP-35 NleNle). One interesting finding is that although a widely accepted model of alanine dipeptide contains six states, a simpler model with only three states is equally good for predicting long-timescale motions. We also used the constructed Markov models to estimate important kinetic and dynamic quantities for protein folding, in particular, mean first-passage time. The results are consistent with available experimental measurements.

  6. Markov dynamic models for long-timescale protein motion.

    KAUST Repository

    Chiang, Tsung-Han; Hsu, David; Latombe, Jean-Claude

    2010-01-01

    Molecular dynamics (MD) simulation is a well-established method for studying protein motion at the atomic scale. However, it is computationally intensive and generates massive amounts of data. One way of addressing the dual challenges of computation efficiency and data analysis is to construct simplified models of long-timescale protein motion from MD simulation data. In this direction, we propose to use Markov models with hidden states, in which the Markovian states represent potentially overlapping probabilistic distributions over protein conformations. We also propose a principled criterion for evaluating the quality of a model by its ability to predict long-timescale protein motions. Our method was tested on 2D synthetic energy landscapes and two extensively studied peptides, alanine dipeptide and the villin headpiece subdomain (HP-35 NleNle). One interesting finding is that although a widely accepted model of alanine dipeptide contains six states, a simpler model with only three states is equally good for predicting long-timescale motions. We also used the constructed Markov models to estimate important kinetic and dynamic quantities for protein folding, in particular, mean first-passage time. The results are consistent with available experimental measurements.

  7. Quantum Adiabatic Optimization and Combinatorial Landscapes

    Science.gov (United States)

    Smelyanskiy, V. N.; Knysh, S.; Morris, R. D.

    2003-01-01

    In this paper we analyze the performance of the Quantum Adiabatic Evolution (QAE) algorithm on a variant of Satisfiability problem for an ensemble of random graphs parametrized by the ratio of clauses to variables, gamma = M / N. We introduce a set of macroscopic parameters (landscapes) and put forward an ansatz of universality for random bit flips. We then formulate the problem of finding the smallest eigenvalue and the excitation gap as a statistical mechanics problem. We use the so-called annealing approximation with a refinement that a finite set of macroscopic variables (verses only energy) is used, and are able to show the existence of a dynamic threshold gamma = gammad, beyond which QAE should take an exponentially long time to find a solution. We compare the results for extended and simplified sets of landscapes and provide numerical evidence in support of our universality ansatz.

  8. Development and application of a free energy force field for all atom protein folding

    International Nuclear Information System (INIS)

    Verma, A.

    2007-11-01

    Proteins are the workhorses of all cellular life. They constitute the building blocks and the machinery of all cells and typically function in specific three-dimensional conformations into which each protein folds. Currently over one million protein sequences are known, compared to about 40,000 structures deposited in the Protein Data Bank (the world-wide database of protein structures). Reliable theoretical methods for protein structure prediction could help to reduce the gap between sequence and structural databases and elucidate the biological information in structurally unresolved sequences. In this thesis we explore an approach for protein structure prediction and folding that is based on the Anfinsen's hypothesis that most proteins in their native state are in thermodynamic equilibrium with their environment. We have developed a free energy forcefield (PFF02) that locates the native conformation of many proteins from all structural classes at the global minimum of the free-energy model. We have validated the forcefield against a large decoy set (Rosetta). The average root mean square deviation (RMSD) for the lowest energy structure for the 32 proteins of the decoy set was only 2.14 Aa from the experimental conformation. We have successfully implemented and used stochastic optimization methods, such as the basin hopping technique and evolutionary algorithms for all atom protein structure prediction. The evolutionary algorithm performs exceptionally well on large supercomputational architectures, such as BlueGene and MareNostrum. Using the PFF02 forcefield, we were able to fold 13 proteins (12-56 amino acids), which include helix, sheet and mixed secondary structure. On average the predicted structure of these proteins deviated from their experimental conformation by only 2.89 Aa RMSD. (orig.)

  9. Effects of Dietary Protein Source and Quantity during Weight Loss on Appetite, Energy Expenditure, and Cardio-Metabolic Responses.

    Science.gov (United States)

    Li, Jia; Armstrong, Cheryl L H; Campbell, Wayne W

    2016-01-26

    Higher protein meals increase satiety and the thermic effect of feeding (TEF) in acute settings, but it is unclear whether these effects remain after a person becomes acclimated to energy restriction or a given protein intake. This study assessed the effects of predominant protein source (omnivorous, beef/pork vs. lacto-ovo vegetarian, soy/legume) and quantity (10%, 20%, or 30% of energy from protein) on appetite, energy expenditure, and cardio-metabolic indices during energy restriction (ER) in overweight and obese adults. Subjects were randomly assigned to one protein source and then consumed diets with different quantities of protein (4 weeks each) in a randomized crossover manner. Perceived appetite ratings (free-living and in-lab), TEF, and fasting cardio-metabolic indices were assessed at the end of each 4-week period. Protein source and quantity did not affect TEF, hunger, or desire to eat, other than a modestly higher daily composite fullness rating with 30% vs. 10% protein diet (p = 0.03). While the 20% and 30% protein diets reduced cholesterol, triacylglycerol, and APO-B vs. 10% protein (p appetite control, energy expenditure and cardio-metabolic risk factors during ER-induced weight loss.

  10. Protein-energy malnutrition alters thermoregulatory homeostasis and the response to brain ischemia.

    Science.gov (United States)

    Smith, Shari E; Prosser-Loose, Erin J; Colbourne, Frederick; Paterson, Phyllis G

    2011-02-01

    Co-existing protein-energy malnutrition (PEM), characterized by deficits in both protein and energy status, impairs functional outcome following global ischemia and has been associated with increased reactive gliosis. Since temperature is a key determinant of brain damage following an ischemic insult, the objective was to investigate whether alterations in post-ischemic temperature regulation contribute to PEM-induced reactive gliosis following ischemia. Male Sprague-Dawley rats (190-280 g) were assigned to either control diet (18% protein) or PEM induced by feeding a low protein diet (2% protein) for 7 days prior to either global ischemia or sham surgery. There was a rapid disruption in thermoregulatory function in rats fed the low protein diet as assessed by continuous recording of core temperature with bio-electrical sensor transmitters. Both daily temperature fluctuation and mean temperature increased within the first 24 hours, and these remained significantly elevated throughout the 7 day pre-ischemic period (p protein diet rapidly impairs the ability to maintain thermoregulatory homeostasis, and the resultant PEM also diminishes the ability to thermoregulate in response to a challenge. Since temperature regulation is a key determinant of brain injury following ischemia, these findings suggest that the pathophysiology of brain injury could be altered in stroke victims with coexisting PEM.

  11. Integrating landscape ecology and geoinformatics to decipher landscape dynamics for regional planning.

    Science.gov (United States)

    Dikou, Angela; Papapanagiotou, Evangelos; Troumbis, Andreas

    2011-09-01

    We used remote sensing and GIS in conjunction with multivariate statistical methods to: (i) quantify landscape composition (land cover types) and configuration (patch density, diversity, fractal dimension, contagion) for five coastal watersheds of Kalloni gulf, Lesvos Island, Greece, in 1945, 1960, 1971, 1990 and 2002/2003, (ii) evaluate the relative importance of physical (slope, geologic substrate, stream order) and human (road network, population density) variables on landscape composition and configuration, and (iii) characterize processes that led to land cover changes through land cover transitions between these five successive periods in time. Distributions of land cover types did not differ among the five time periods at the five watersheds studied because the largest cumulative changes between 1945 and 2002/2003 did not take place at dominant land cover types. Landscape composition related primarily to the physical attributes of the landscape. Nevertheless, increase in population density and the road network were found to increase heterogeneity of the landscape mosaic (patchiness), complexity of patch shape (fractal dimension), and patch disaggregation (contagion). Increase in road network was also found to increase landscape diversity due to the creation of new patches. The main processes involved in land cover changes were plough-land abandonment and ecological succession. Landscape dynamics during the last 50 years corroborate the ecotouristic-agrotouristic model for regional development to reverse trends in agricultural land abandonment and human population decline and when combined with hypothetical regulatory approaches could predict how this landscape could develop in the future, thus, providing a valuable tool to regional planning.

  12. Condensed landscape experience

    DEFF Research Database (Denmark)

    Earon, Ofri

    2011-01-01

    demands, quality of space, mixture of functions, urban complexity, public life and cultural heritage. In order to launch such an approach, an understanding of the spatial, social and environmental significance of a radical re-thinking of relationships between architecture and landscape is necessary...... is becoming a standard in contemporary architecture. Merging architecture and landscape has turned into a principle for an ecological / sustainable architecture. Yet, my aspiration is to achieve a wider interaction involving an application of a wider range of perspectives, such as: urban identity, social......‘Re-thinking interaction between landscape and urban buildings’ participates in an interdisciplinary discourse about the theoretical and practical advantages of openly juxtaposing landscape and architecture without having one more advanced in importance. Recently, the greenification of buildings...

  13. Model test on the relationship feed energy and protein ratio to the production and quality of milk protein

    Science.gov (United States)

    Hartanto, R.; Jantra, M. A. C.; Santosa, S. A. B.; Purnomoadi, A.

    2018-01-01

    The purpose of this research was to find an appropriate relationship model between the feed energy and protein ratio with the amount of production and quality of milk proteins. This research was conducted at Getasan Sub-district, Semarang Regency, Central Java Province, Indonesia using 40 samples (Holstein Friesian cattle, lactation period II-III and lactation month 3-4). Data were analyzed using linear and quadratic regressions, to predict the production and quality of milk protein from feed energy and protein ratio that describe the diet. The significance of model was tested using analysis of variance. Coefficient of determination (R2), residual variance (RV) and root mean square prediction error (RMSPE) were reported for the developed equations as an indicator of the goodness of model fit. The results showed no relationship in milk protein (kg), milk casein (%), milk casein (kg) and milk urea N (mg/dl) as function of CP/TDN. The significant relationship was observed in milk production (L or kg) and milk protein (%) as function of CP/TDN, both in linear and quadratic models. In addition, a quadratic change in milk production (L) (P = 0.003), milk production (kg) (P = 0.003) and milk protein concentration (%) (P = 0.026) were observed with increase of CP/TDN. It can be concluded that quadratic equation was the good fitting model for this research, because quadratic equation has larger R2, smaller RV and smaller RMSPE than those of linear equation.

  14. Protein energy malnutrition impairs homeostatic proliferation of memory CD8 T cells.

    Science.gov (United States)

    Iyer, Smita S; Chatraw, Janel Hart; Tan, Wendy G; Wherry, E John; Becker, Todd C; Ahmed, Rafi; Kapasi, Zoher F

    2012-01-01

    Nutrition is a critical but poorly understood determinant of immunity. There is abundant epidemiological evidence linking protein malnutrition to impaired vaccine efficacy and increased susceptibility to infections; yet, the role of dietary protein in immune memory homeostasis remains poorly understood. In this study, we show that protein-energy malnutrition induced in mice by low-protein (LP) feeding has a detrimental impact on CD8 memory. Relative to adequate protein (AP)-fed controls, LP feeding in lymphocytic choriomeningitis virus (LCMV)-immune mice resulted in a 2-fold decrease in LCMV-specific CD8 memory T cells. Adoptive transfer of memory cells, labeled with a division tracking dye, from AP mice into naive LP or AP mice demonstrated that protein-energy malnutrition caused profound defects in homeostatic proliferation. Remarkably, this defect occurred despite the lymphopenic environment in LP hosts. Whereas Ag-specific memory cells in LP and AP hosts were phenotypically similar, memory cells in LP hosts were markedly less responsive to polyinosinic-polycytidylic acid-induced acute proliferative signals. Furthermore, upon recall, memory cells in LP hosts displayed reduced proliferation and protection from challenge with LCMV-clone 13, resulting in impaired viral clearance in the liver. The findings show a metabolic requirement of dietary protein in sustaining functional CD8 memory and suggest that interventions to optimize dietary protein intake may improve vaccine efficacy in malnourished individuals.

  15. Noninvasive imaging of protein-protein interactions from live cells and living subjects using bioluminescence resonance energy transfer.

    Science.gov (United States)

    De, Abhijit; Gambhir, Sanjiv Sam

    2005-12-01

    This study demonstrates a significant advancement of imaging of a distance-dependent physical process, known as the bioluminescent resonance energy transfer (BRET2) signal in living subjects, by using a cooled charge-coupled device (CCD) camera. A CCD camera-based spectral imaging strategy enables simultaneous visualization and quantitation of BRET signal from live cells and cells implanted in living mice. We used the BRET2 system, which utilizes Renilla luciferase (hRluc) protein and its substrate DeepBlueC (DBC) as an energy donor and a mutant green fluorescent protein (GFP2) as the acceptor. To accomplish this objective in this proof-of-principle study, the donor and acceptor proteins were fused to FKBP12 and FRB, respectively, which are known to interact only in the presence of the small molecule mediator rapamycin. Mammalian cells expressing these fusion constructs were imaged using a cooled-CCD camera either directly from culture dishes or by implanting them into mice. By comparing the emission photon yields in the presence and absence of rapamycin, the specific BRET signal was determined. The CCD imaging approach of BRET signal is particularly appealing due to its capacity to seamlessly bridge the gap between in vitro and in vivo studies. This work validates BRET as a powerful tool for interrogating and observing protein-protein interactions directly at limited depths in living mice.

  16. Hessian eigenvalue distribution in a random Gaussian landscape

    Science.gov (United States)

    Yamada, Masaki; Vilenkin, Alexander

    2018-03-01

    The energy landscape of multiverse cosmology is often modeled by a multi-dimensional random Gaussian potential. The physical predictions of such models crucially depend on the eigenvalue distribution of the Hessian matrix at potential minima. In particular, the stability of vacua and the dynamics of slow-roll inflation are sensitive to the magnitude of the smallest eigenvalues. The Hessian eigenvalue distribution has been studied earlier, using the saddle point approximation, in the leading order of 1/ N expansion, where N is the dimensionality of the landscape. This approximation, however, is insufficient for the small eigenvalue end of the spectrum, where sub-leading terms play a significant role. We extend the saddle point method to account for the sub-leading contributions. We also develop a new approach, where the eigenvalue distribution is found as an equilibrium distribution at the endpoint of a stochastic process (Dyson Brownian motion). The results of the two approaches are consistent in cases where both methods are applicable. We discuss the implications of our results for vacuum stability and slow-roll inflation in the landscape.

  17. Protein-Energy Wasting and Mortality in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Ezio Gianetta

    2011-05-01

    Full Text Available Protein-energy wasting (PEW is common in patients with chronic kidney disease (CKD and is associated with an increased death risk from cardiovascular diseases. However, while even minor renal dysfunction is an independent predictor of adverse cardiovascular prognosis, PEW becomes clinically manifest at an advanced stage, early before or during the dialytic stage. Mechanisms causing loss of muscle protein and fat are complex and not always associated with anorexia, but are linked to several abnormalities that stimulate protein degradation and/or decrease protein synthesis. In addition, data from experimental CKD indicate that uremia specifically blunts the regenerative potential in skeletal muscle, by acting on muscle stem cells. In this discussion recent findings regarding the mechanisms responsible for malnutrition and the increase in cardiovascular risk in CKD patients are discussed. During the course of CKD, the loss of kidney excretory and metabolic functions proceed together with the activation of pathways of endothelial damage, inflammation, acidosis, alterations in insulin signaling and anorexia which are likely to orchestrate net protein catabolism and the PEW syndrome.

  18. Visualization of landscape changes and threatening environmental processes using a digital landscape model

    International Nuclear Information System (INIS)

    Svatonova, H; Rybansky, M

    2014-01-01

    Visualizations supported by new geoinformation technologies prove to be appropriate tools for presenting and sharing the research results by professional and general public. The object of the research was to evaluate the benefits of visualizations for the nonexpert users. The subject of evaluation was: the success rate of interpreting the information; forming of a realistic idea of the unknown landscape; and the preference of the users during selection of the appropriate visualization for the purpose of solving the task. The tasks concerned: assessing the current situation and changes of the landscape; assessing the erosion in the landscape; and the ways of their visualizing. To prepare and process the landscape visualizations, it was necessary to select areas that allow tracking of land use changes and representative environmental processes. Then the digital landscape model was created and a number of visualizations were generated. The results of visualization testing show that the users prefer maps to orthophotos, they are able to formulate correct statements concerning the landscape with the help of visualizations, and that the simulated fly throughs represent a very suitable tool supporting formation of a realistic ideas about the landscape

  19. Reverse triiodothyronine in protein energy malnutrition

    Energy Technology Data Exchange (ETDEWEB)

    Hafiez, A A; Abdel-Salam, E; Abbas, E Z; Halawa, F A; El-Hefnawy, N [Cairo Univ. (Egypt)

    1984-08-01

    Serum levels of thyroxine (T/sub 4/), triiodothyronine (T/sub 3/), reverse triiodothyronine (rT/sub 3/) and thyrotropin (TSH) were determined in cases of kwashiorkor and marasmus. Decreased levels of T/sub 4/ and T/sub 3/, and increased levels of rT/sub 3/ with no change in TSH were obtained. Thus in infants suffering from protein energy malnutrition there is a state of thyroid dysfunction as well as a shift in the peripheral T/sub 4/ metabolism being converted to the inert rT/sub 3/ rather than to the physiologically active T/sub 3/.

  20. Identifying reliable predictors of protein-energy malnutrition in hospitalized frail older adults. A prospective longitudinal study.

    Science.gov (United States)

    Sanson, Gianfranco; Bertocchi, Luca; Dal Bo, Eugenia; Di Pasquale, Carmen Luisa; Zanetti, Michela

    2018-03-07

    Decreased food intake is a risk factor for relevant complications (e.g. infections, pressure ulcers), longer hospital stays, higher readmission rates, greater health care costs and increased patient mortality, particularly in frail hospitalized older adults who are malnourished or at risk of malnutrition. Nurses are called to improve this criticality, starting from accurately identify patients for malnutrition at hospital admission and effectively monitoring their food intake. The primary aim was to identify reliable predictive indicators of reduced food intake at hospital admission. The secondary aims were to assess the adequacy of daily energy and protein intake and the impact of nutrient intake on patient outcomes. Prospective observational longitudinal study. Internal Medicine Ward of an Academic Teaching University Hospital. Acute older adults who were malnourished or at risk of malnutrition (Nutritional Risk Score-2002 ≥ 3, middle-upper arm circumference energy and protein intake was monitored during the first 5 days of hospital stay by a photographic method and compared to the daily energy and protein requirement calculated by specific equations. Data on anthropometry, inflammation/malnutrition laboratory data and body composition (phase angle calculated using bioelectrical impedance analysis) were collected. Eighty-one subjects (age 81.5 ± 11.5 years) were enrolled. Mean energy intake was 669.0 ± 573.9 kcal/day, and mean protein intake was 30.7 ± 25.8 g/day. Over 60% of patients ingested ≤50% of their calculated energy and protein requirements: these patients were older (p = 0.026), had a lower middle-upper arm circumference (p = 0.022) and total arm area (p = 0.038), a higher C-reactive protein/albumin ratio and Instant Nutritional Assessment score (p protein/albumin ratio, and impaired self-feeding at admission were independently associated with critically reduced energy and protein intake. Middle

  1. Determinants of protein-energy malnutrition in community-dwelling older adults: a systematic review of observational studies.

    Science.gov (United States)

    van der Pols-Vijlbrief, Rachel; Wijnhoven, Hanneke A H; Schaap, Laura A; Terwee, Caroline B; Visser, Marjolein

    2014-11-01

    Protein-energy malnutrition is associated with numerous poor health outcomes, including high health care costs, mortality rates and poor physical functioning in older adults. This systematic literature review aims to identify and provide an evidence based overview of potential determinants of protein-energy malnutrition in community-dwelling older adults. A systematic search was conducted in PUBMED, EMBASE, CINAHL and COCHRANE from the earliest possible date through January 2013. Observational studies that examined determinants of protein-energy malnutrition were selected and a best evidence synthesis was performed to summarize the results. In total 28 studies were included in this review from which 122 unique potential determinants were derived. Thirty-seven determinants were examined in sufficient number of studies and were included in a best evidence synthesis. The best evidence score comprised design (cross-sectional, longitudinal) and quality of the study (high, moderate) to grade the evidence level. Strong evidence for an association with protein-energy malnutrition was found for poor appetite, and moderate evidence for edentulousness, having no diabetes, hospitalization and poor self-reported health. Strong evidence for no association was found for anxiety, chewing difficulty, few friends, living alone, feeling lonely, death of spouse, high number of diseases, heart failure and coronary failure, stroke (CVA) and the use of anti-inflammatory medications. This review shows that protein-energy malnutrition is a multifactorial problem and that different domains likely play a role in the pathway of developing protein-energy malnutrition. These results provide important knowledge for the development of targeted, multifactorial interventions that aim to prevent the development of protein-energy malnutrition in community-dwelling older adults. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Effects of protein and energy deficiency on the incorporation of /sup 14/C-Chlorella protein hydrolysate into body constituents of adult rats

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, S; Wakabayashi, K; Niiyama, Y; Inoue, G [Tokushima Univ. (Japan). School of Medicine

    1974-12-01

    The effects of protein and/or energy deficiency on /sup 14/C incorporation into body constituents and /sup 14/C output in expired air and urine were investigated in adult rats using /sup 14/C-Chlorella protein hydrolysate. Rats were given a protein-free diet (PFD) for 2 weeks and conrol rats were fed ad libitum or pari-fed with the PFD group on a 12% lactalbumin diet (LA and Pair-fed, respectively). On the 15th day, animals received /sup 14/C-Chlorella protein hydolysate with 5 g of their respective diet. One group of PFD animals was given tracer by stomach tube without food (PFD-fast). Normal control rats ate about twice as much diet as the PFD group. The respiratory /sup 14/C output in the PFD group was identical with those in the LA and Pair-fed groups and was less than that in the PFD-fast group. The rate of protein synthesis, provisionally expressed as relative specific radioactivity, was more in the PFD group than in the normal group in the liver and less than the latter in the muscle. The LA group retained less total radioactivity in the body than the Pair-fed or PFD group, indicating high capability to hold the body protein in protein deficiency. In addition, decreased conversion of amino acids to lipids and glycogen was observed in the PFD group. All these differences are interpreted as adaptations to protein shortage. On prolonged fasting (PFD-fast group), gluconeogenesis in the liver increased to provide energy, despite the protein deficiency. The relative importances of protein and energy for tissue protein synthesis are briefly discussed.

  3. Landscape genetics and limiting factors

    Science.gov (United States)

    Samuel A. Cushman; Andrew J. Shirk; Erin L. Landguth

    2013-01-01

    Population connectivity is mediated by the movement of organisms or propagules through landscapes. However, little is known about how variation in the pattern of landscape mosaics affects the detectability of landscape genetic relationships. The goal of this paper is to explore the impacts of limiting factors on landscape genetic processes using simulation...

  4. Evaluation of Docking Target Functions by the Comprehensive Investigation of Protein-Ligand Energy Minima.

    Science.gov (United States)

    Oferkin, Igor V; Katkova, Ekaterina V; Sulimov, Alexey V; Kutov, Danil C; Sobolev, Sergey I; Voevodin, Vladimir V; Sulimov, Vladimir B

    2015-01-01

    The adequate choice of the docking target function impacts the accuracy of the ligand positioning as well as the accuracy of the protein-ligand binding energy calculation. To evaluate a docking target function we compared positions of its minima with the experimentally known pose of the ligand in the protein active site. We evaluated five docking target functions based on either the MMFF94 force field or the PM7 quantum-chemical method with or without implicit solvent models: PCM, COSMO, and SGB. Each function was tested on the same set of 16 protein-ligand complexes. For exhaustive low-energy minima search the novel MPI parallelized docking program FLM and large supercomputer resources were used. Protein-ligand binding energies calculated using low-energy minima were compared with experimental values. It was demonstrated that the docking target function on the base of the MMFF94 force field in vacuo can be used for discovery of native or near native ligand positions by finding the low-energy local minima spectrum of the target function. The importance of solute-solvent interaction for the correct ligand positioning is demonstrated. It is shown that docking accuracy can be improved by replacement of the MMFF94 force field by the new semiempirical quantum-chemical PM7 method.

  5. Evaluation of Docking Target Functions by the Comprehensive Investigation of Protein-Ligand Energy Minima

    Directory of Open Access Journals (Sweden)

    Igor V. Oferkin

    2015-01-01

    Full Text Available The adequate choice of the docking target function impacts the accuracy of the ligand positioning as well as the accuracy of the protein-ligand binding energy calculation. To evaluate a docking target function we compared positions of its minima with the experimentally known pose of the ligand in the protein active site. We evaluated five docking target functions based on either the MMFF94 force field or the PM7 quantum-chemical method with or without implicit solvent models: PCM, COSMO, and SGB. Each function was tested on the same set of 16 protein-ligand complexes. For exhaustive low-energy minima search the novel MPI parallelized docking program FLM and large supercomputer resources were used. Protein-ligand binding energies calculated using low-energy minima were compared with experimental values. It was demonstrated that the docking target function on the base of the MMFF94 force field in vacuo can be used for discovery of native or near native ligand positions by finding the low-energy local minima spectrum of the target function. The importance of solute-solvent interaction for the correct ligand positioning is demonstrated. It is shown that docking accuracy can be improved by replacement of the MMFF94 force field by the new semiempirical quantum-chemical PM7 method.

  6. Condensed landscape experience

    DEFF Research Database (Denmark)

    Earon, Ofri

    2011-01-01

    ‘Re-thinking interaction between landscape and urban buildings’ participates in an interdisciplinary discourse about the theoretical and practical advantages of openly juxtaposing landscape and architecture without having one more advanced in importance. Recently, the greenification of buildings...... demands, quality of space, mixture of functions, urban complexity, public life and cultural heritage. In order to launch such an approach, an understanding of the spatial, social and environmental significance of a radical re-thinking of relationships between architecture and landscape is necessary...

  7. Effects of Dietary Protein Source and Quantity during Weight Loss on Appetite, Energy Expenditure, and Cardio-Metabolic Responses

    Directory of Open Access Journals (Sweden)

    Jia Li

    2016-01-01

    Full Text Available Higher protein meals increase satiety and the thermic effect of feeding (TEF in acute settings, but it is unclear whether these effects remain after a person becomes acclimated to energy restriction or a given protein intake. This study assessed the effects of predominant protein source (omnivorous, beef/pork vs. lacto-ovo vegetarian, soy/legume and quantity (10%, 20%, or 30% of energy from protein on appetite, energy expenditure, and cardio-metabolic indices during energy restriction (ER in overweight and obese adults. Subjects were randomly assigned to one protein source and then consumed diets with different quantities of protein (4 weeks each in a randomized crossover manner. Perceived appetite ratings (free-living and in-lab, TEF, and fasting cardio-metabolic indices were assessed at the end of each 4-week period. Protein source and quantity did not affect TEF, hunger, or desire to eat, other than a modestly higher daily composite fullness rating with 30% vs. 10% protein diet (p = 0.03. While the 20% and 30% protein diets reduced cholesterol, triacylglycerol, and APO-B vs. 10% protein (p < 0.05, protein source did not affect cardio-metabolic indices. In conclusion, diets varying in protein quantity with either beef/pork or soy/legume as the predominant source have minimal effects on appetite control, energy expenditure and cardio-metabolic risk factors during ER-induced weight loss.

  8. Effect of feeding different level of protein and energy in some minerals of the Nubian goats in the Sudan

    International Nuclear Information System (INIS)

    Elmansoury, Y.H.A.; Mahagoub, M.M.; Elbashir, H.M.

    2010-01-01

    Forty four adult female Nubian goats 2-4 years of age were divided into four equal groups of ten animals. Each group was offered a ration containing energy (E) and protein (P) at levels that were either high (H) or low (L). The groups were designated as high energy: high protein (HEHP), low energy: low protein (LELP), high energy: low protein (HELP) and low energy: low protein (LEHP) respectively. Blood samples from all goats were collected at weekly intervals for minerals analysis. Water and food were offered adlib. The instrumental neutron activation analysis (lNAA) was used for the determination of the concentration values for Co which were 0.0279±0.0l2, 0.0212±0.0l5, 0.0378±0.021, and 0.0284 ±0.0l5 and for Fe 25.705±0.002, 35.54±0.013, 24.75±0.03 and 45.75±0.023 whereas for Se 1.042±0.023, 0.9333±0.013, 0.8606 ±0.011 and 1.101025±0.012 for HEHP, LELP, HELP and LEHP respectively. It could be seen that Co reached the lowest with the low energy low protein ration. Fe although tended to decrease with the high energy low protein, it almost doubled with low energy high protein concentration in the diet. Se seemed not to be affected by the energy and protein levels in the diet.

  9. Sculpting proteins interactively: continual energy minimization embedded in a graphical modeling system.

    Science.gov (United States)

    Surles, M C; Richardson, J S; Richardson, D C; Brooks, F P

    1994-02-01

    We describe a new paradigm for modeling proteins in interactive computer graphics systems--continual maintenance of a physically valid representation, combined with direct user control and visualization. This is achieved by a fast algorithm for energy minimization, capable of real-time performance on all atoms of a small protein, plus graphically specified user tugs. The modeling system, called Sculpt, rigidly constrains bond lengths, bond angles, and planar groups (similar to existing interactive modeling programs), while it applies elastic restraints to minimize the potential energy due to torsions, hydrogen bonds, and van der Waals and electrostatic interactions (similar to existing batch minimization programs), and user-specified springs. The graphical interface can show bad and/or favorable contacts, and individual energy terms can be turned on or off to determine their effects and interactions. Sculpt finds a local minimum of the total energy that satisfies all the constraints using an augmented Lagrange-multiplier method; calculation time increases only linearly with the number of atoms because the matrix of constraint gradients is sparse and banded. On a 100-MHz MIPS R4000 processor (Silicon Graphics Indigo), Sculpt achieves 11 updates per second on a 20-residue fragment and 2 updates per second on an 80-residue protein, using all atoms except non-H-bonding hydrogens, and without electrostatic interactions. Applications of Sculpt are described: to reverse the direction of bundle packing in a designed 4-helix bundle protein, to fold up a 2-stranded beta-ribbon into an approximate beta-barrel, and to design the sequence and conformation of a 30-residue peptide that mimics one partner of a protein subunit interaction. Computer models that are both interactive and physically realistic (within the limitations of a given force field) have 2 significant advantages: (1) they make feasible the modeling of very large changes (such as needed for de novo design), and

  10. Energy Landscapes: From Protein Folding to Molecular Assembly

    Science.gov (United States)

    Databases National Security Education Center (NSEC) Center for Nonlinear Studies Engineering Institute assembly is very common in biology and in nanotechnology. Simple examples of self-assembly are the folding efflux pump machinery, ATP synthase, the ribosome, and many others. In nanotechnology, self-assembly has

  11. Mitochondrial uncoupling proteins and energy metabolism

    Directory of Open Access Journals (Sweden)

    Rosa Anna Busiello

    2015-02-01

    Full Text Available Understanding the metabolic factors that contribute to energy metabolism (EM is critical for the development of new treatments for obesity and related diseases. Mitochondrial oxidative phosphorylation is not perfectly coupled to ATP synthesis, and the process of proton-leak plays a crucial role. Proton-leak accounts for a significant part of the resting metabolic rate and therefore enhancement of this process represents a potential target for obesity treatment. Since their discovery, uncoupling proteins have stimulated great interest due to their involvement in mitochondrial-inducible proton-leak. Despite the widely accepted uncoupling/thermogenic effect of uncoupling protein one (UCP1, which was the first in this family to be discovered, the reactions catalyzed by its homologue UCP3 and the physiological role remain under debate.This review provides an overview of the role played by UCP1 and UCP3 in mitochondrial uncoupling/functionality as well as EM and suggests that they are a potential therapeutic target for treating obesity and its related diseases such as type II diabetes mellitus.

  12. Pronounced energy restriction with elevated protein intake results in no change in proteolysis and reductions in skeletal muscle protein synthesis that are mitigated by resistance exercise.

    Science.gov (United States)

    Hector, Amy J; McGlory, Chris; Damas, Felipe; Mazara, Nicole; Baker, Steven K; Phillips, Stuart M

    2018-01-01

    Preservation of lean body mass (LBM) may be important during dietary energy restriction (ER) and requires equal rates of muscle protein synthesis (MPS) and muscle protein breakdown (MPB). Currently, the relative contribution of MPS and MPB to the loss of LBM during ER in humans is unknown. We aimed to determine the impact of dietary protein intake and resistance exercise on MPS and MPB during a controlled short-term energy deficit. Adult men (body mass index, 28.6 ± 0.6 kg/m 2 ; age 22 ± 1 yr) underwent 10 d of 40%-reduced energy intake while performing unilateral resistance exercise and consuming lower protein (1.2 g/kg/d, n = 12) or higher protein (2.4 g/kg/d, n = 12). Pre- and postintervention testing included dual-energy X-ray absorptiometry, primed constant infusion of ring -[ 13 C 6 ]phenylalanine, and 15 [N]phenylalanine to measure acute postabsorptive MPS and MPB; D 2 O to measure integrated MPS; and gene and protein expression. There was a decrease in acute MPS after ER (higher protein, 0.059 ± 0.006 to 0.051 ± 0.009%/h; lower protein, 0.061 ± 0.005 to 0.045 ± 0.006%/h; P resistance exercise (higher protein, 0.067 ± 0.01%/h; lower protein, 0.061 ± 0.006%/h), and integrated MPS followed a similar pattern. There was no change in MPB (energy balance, 0.080 ± 0.01%/hr; ER rested legs, 0.078 ± 0.008%/hr; ER exercised legs, 0.079 ± 0.006%/hr). We conclude that a reduction in MPS is the main mechanism that underpins LBM loss early in ER in adult men.-Hector, A. J., McGlory, C., Damas, F., Mazara, N., Baker, S. K., Phillips, S. M. Pronounced energy restriction with elevated protein intake results in no change in proteolysis and reductions in skeletal muscle protein synthesis that are mitigated by resistance exercise. © FASEB.

  13. Machine learning landscapes and predictions for patient outcomes

    Science.gov (United States)

    Das, Ritankar; Wales, David J.

    2017-07-01

    The theory and computational tools developed to interpret and explore energy landscapes in molecular science are applied to the landscapes defined by local minima for neural networks. These machine learning landscapes correspond to fits of training data, where the inputs are vital signs and laboratory measurements for a database of patients, and the objective is to predict a clinical outcome. In this contribution, we test the predictions obtained by fitting to single measurements, and then to combinations of between 2 and 10 different patient medical data items. The effect of including measurements over different time intervals from the 48 h period in question is analysed, and the most recent values are found to be the most important. We also compare results obtained for neural networks as a function of the number of hidden nodes, and for different values of a regularization parameter. The predictions are compared with an alternative convex fitting function, and a strong correlation is observed. The dependence of these results on the patients randomly selected for training and testing decreases systematically with the size of the database available. The machine learning landscapes defined by neural network fits in this investigation have single-funnel character, which probably explains why it is relatively straightforward to obtain the global minimum solution, or a fit that behaves similarly to this optimal parameterization.

  14. A single cysteine post-translational oxidation suffices to compromise globular proteins kinetic stability and promote amyloid formation

    Directory of Open Access Journals (Sweden)

    Patrizia Marinelli

    2018-04-01

    Full Text Available Oxidatively modified forms of proteins accumulate during aging. Oxidized protein conformers might act as intermediates in the formation of amyloids in age-related disorders. However, it is not known whether this amyloidogenic conversion requires an extensive protein oxidative damage or it can be promoted just by a discrete, localized post-translational modification of certain residues. Here, we demonstrate that the irreversible oxidation of a single free Cys suffices to severely perturb the folding energy landscape of a stable globular protein, compromise its kinetic stability, and lead to the formation of amyloids under physiological conditions. Experiments and simulations converge to indicate that this specific oxidation-promoted protein aggregation requires only local unfolding. Indeed, a large scale analysis indicates that many cellular proteins are at risk of undergoing this kind of deleterious transition; explaining how oxidative stress can impact cell proteostasis and subsequently lead to the onset of pathological states. Keywords: Protein oxidation, Protein misfolding, Protein aggregation, Oxidative stress, Post-translational modification

  15. Rich RNA Structure Landscapes Revealed by Mutate-and-Map Analysis.

    Directory of Open Access Journals (Sweden)

    Pablo Cordero

    2015-11-01

    Full Text Available Landscapes exhibiting multiple secondary structures arise in natural RNA molecules that modulate gene expression, protein synthesis, and viral infection [corrected]. We report herein that high-throughput chemical experiments can isolate an RNA's multiple alternative secondary structures as they are stabilized by systematic mutagenesis (mutate-and-map, M2 and that a computational algorithm, REEFFIT, enables unbiased reconstruction of these states' structures and populations. In an in silico benchmark on non-coding RNAs with complex landscapes, M2-REEFFIT recovers 95% of RNA helices present with at least 25% population while maintaining a low false discovery rate (10% and conservative error estimates. In experimental benchmarks, M2-REEFFIT recovers the structure landscapes of a 35-nt MedLoop hairpin, a 110-nt 16S rRNA four-way junction with an excited state, a 25-nt bistable hairpin, and a 112-nt three-state adenine riboswitch with its expression platform, molecules whose characterization previously required expert mutational analysis and specialized NMR or chemical mapping experiments. With this validation, M2-REEFFIT enabled tests of whether artificial RNA sequences might exhibit complex landscapes in the absence of explicit design. An artificial flavin mononucleotide riboswitch and a randomly generated RNA sequence are found to interconvert between three or more states, including structures for which there was no design, but that could be stabilized through mutations. These results highlight the likely pervasiveness of rich landscapes with multiple secondary structures in both natural and artificial RNAs and demonstrate an automated chemical/computational route for their empirical characterization.

  16. The Value of Landscape Essence

    Directory of Open Access Journals (Sweden)

    Maria da Conceição Marques Freire

    2014-08-01

    Full Text Available A new approach to interpreting the landscape is examined by accepting its complexity through inductive reasoning. While attempting to identify the essence of the landscape in the city and municipality of Óbidos, Portugal, several architectural recommendations of Venturi (2004 have been adapted as a framework for understanding this landscape. These will then guide the process of landscape transformation through:•••using the concepts of closed and contained spaces and the concept of fluid space;•recognising the existence of interstitial open spaces;•using those elements which are common to the distinct typologies of space;•defining the components that should be respected and those that can be respected;•observing landscape as a whole , while emphasising the relationship between the parts and the whole; and•rejecting simplification in the landscape transformation process.valuing the ambiguity incorporating the complexity Underlying this approach is the belief that the process of transformation must be based on the essence of each landscape. This implies the use of elements and structures of the landscape which are related to ecological, morphological and cultural systems. These elements and structures represent points of reference which should be considered in the process of landscape transformation.

  17. Landscape genetics as a tool for conservation planning: predicting the effects of landscape change on gene flow.

    Science.gov (United States)

    van Strien, Maarten J; Keller, Daniela; Holderegger, Rolf; Ghazoul, Jaboury; Kienast, Felix; Bolliger, Janine

    2014-03-01

    For conservation managers, it is important to know whether landscape changes lead to increasing or decreasing gene flow. Although the discipline of landscape genetics assesses the influence of landscape elements on gene flow, no studies have yet used landscape-genetic models to predict gene flow resulting from landscape change. A species that has already been severely affected by landscape change is the large marsh grasshopper (Stethophyma grossum), which inhabits moist areas in fragmented agricultural landscapes in Switzerland. From transects drawn between all population pairs within maximum dispersal distance (landscape composition as well as some measures of habitat configuration. Additionally, a complete sampling of all populations in our study area allowed incorporating measures of population topology. These measures together with the landscape metrics formed the predictor variables in linear models with gene flow as response variable (F(ST) and mean pairwise assignment probability). With a modified leave-one-out cross-validation approach, we selected the model with the highest predictive accuracy. With this model, we predicted gene flow under several landscape-change scenarios, which simulated construction, rezoning or restoration projects, and the establishment of a new population. For some landscape-change scenarios, significant increase or decrease in gene flow was predicted, while for others little change was forecast. Furthermore, we found that the measures of population topology strongly increase model fit in landscape genetic analysis. This study demonstrates the use of predictive landscape-genetic models in conservation and landscape planning.

  18. Relationships between avian richness and landscape structure at multiple scales using multiple landscapes

    Science.gov (United States)

    Michael S. Mitchell; Scott H. Rutzmoser; T. Bently Wigley; Craig Loehle; John A. Gerwin; Patrick D. Keyser; Richard A. Lancia; Roger W. Perry; Christopher L. Reynolds; Ronald E. Thill; Robert Weih; Don White; Petra Bohall Wood

    2006-01-01

    Little is known about factors that structure biodiversity on landscape scales, yet current land management protocols, such as forest certification programs, place an increasing emphasis on managing for sustainable biodiversity at landscape scales. We used a replicated landscape study to evaluate relationships between forest structure and avian diversity at both stand...

  19. Landscape Ecology

    DEFF Research Database (Denmark)

    Christensen, Andreas Aagaard; Brandt, Jesper; Svenningsen, Stig Roar

    2017-01-01

    , and the ecological significance of the patterns which are generated by such processes. In landscape ecology, perspectives drawn from existing academic disciplines are integrated based on a common, spatially explicit mode of analysis developed from classical holistic geography, emphasizing spatial and landscape...... to translate positivist readings of the environment and hermeneutical perspectives on socioecological interaction into a common framework or terminology....

  20. Energy Minimization of Discrete Protein Titration State Models Using Graph Theory

    Science.gov (United States)

    Purvine, Emilie; Monson, Kyle; Jurrus, Elizabeth; Star, Keith; Baker, Nathan A.

    2016-01-01

    There are several applications in computational biophysics which require the optimization of discrete interacting states; e.g., amino acid titration states, ligand oxidation states, or discrete rotamer angles. Such optimization can be very time-consuming as it scales exponentially in the number of sites to be optimized. In this paper, we describe a new polynomial-time algorithm for optimization of discrete states in macromolecular systems. This algorithm was adapted from image processing and uses techniques from discrete mathematics and graph theory to restate the optimization problem in terms of “maximum flow-minimum cut” graph analysis. The interaction energy graph, a graph in which vertices (amino acids) and edges (interactions) are weighted with their respective energies, is transformed into a flow network in which the value of the minimum cut in the network equals the minimum free energy of the protein, and the cut itself encodes the state that achieves the minimum free energy. Because of its deterministic nature and polynomial-time performance, this algorithm has the potential to allow for the ionization state of larger proteins to be discovered. PMID:27089174

  1. Energy Minimization of Discrete Protein Titration State Models Using Graph Theory.

    Science.gov (United States)

    Purvine, Emilie; Monson, Kyle; Jurrus, Elizabeth; Star, Keith; Baker, Nathan A

    2016-08-25

    There are several applications in computational biophysics that require the optimization of discrete interacting states, for example, amino acid titration states, ligand oxidation states, or discrete rotamer angles. Such optimization can be very time-consuming as it scales exponentially in the number of sites to be optimized. In this paper, we describe a new polynomial time algorithm for optimization of discrete states in macromolecular systems. This algorithm was adapted from image processing and uses techniques from discrete mathematics and graph theory to restate the optimization problem in terms of "maximum flow-minimum cut" graph analysis. The interaction energy graph, a graph in which vertices (amino acids) and edges (interactions) are weighted with their respective energies, is transformed into a flow network in which the value of the minimum cut in the network equals the minimum free energy of the protein and the cut itself encodes the state that achieves the minimum free energy. Because of its deterministic nature and polynomial time performance, this algorithm has the potential to allow for the ionization state of larger proteins to be discovered.

  2. Identification of DNA-binding protein target sequences by physical effective energy functions: free energy analysis of lambda repressor-DNA complexes.

    Directory of Open Access Journals (Sweden)

    Caselle Michele

    2007-09-01

    Full Text Available Abstract Background Specific binding of proteins to DNA is one of the most common ways gene expression is controlled. Although general rules for the DNA-protein recognition can be derived, the ambiguous and complex nature of this mechanism precludes a simple recognition code, therefore the prediction of DNA target sequences is not straightforward. DNA-protein interactions can be studied using computational methods which can complement the current experimental methods and offer some advantages. In the present work we use physical effective potentials to evaluate the DNA-protein binding affinities for the λ repressor-DNA complex for which structural and thermodynamic experimental data are available. Results The binding free energy of two molecules can be expressed as the sum of an intermolecular energy (evaluated using a molecular mechanics forcefield, a solvation free energy term and an entropic term. Different solvation models are used including distance dependent dielectric constants, solvent accessible surface tension models and the Generalized Born model. The effect of conformational sampling by Molecular Dynamics simulations on the computed binding energy is assessed; results show that this effect is in general negative and the reproducibility of the experimental values decreases with the increase of simulation time considered. The free energy of binding for non-specific complexes, estimated using the best energetic model, agrees with earlier theoretical suggestions. As a results of these analyses, we propose a protocol for the prediction of DNA-binding target sequences. The possibility of searching regulatory elements within the bacteriophage λ genome using this protocol is explored. Our analysis shows good prediction capabilities, even in absence of any thermodynamic data and information on the naturally recognized sequence. Conclusion This study supports the conclusion that physics-based methods can offer a completely complementary

  3. Statistical predictions from anarchic field theory landscapes

    International Nuclear Information System (INIS)

    Balasubramanian, Vijay; Boer, Jan de; Naqvi, Asad

    2010-01-01

    Consistent coupling of effective field theories with a quantum theory of gravity appears to require bounds on the rank of the gauge group and the amount of matter. We consider landscapes of field theories subject to such to boundedness constraints. We argue that appropriately 'coarse-grained' aspects of the randomly chosen field theory in such landscapes, such as the fraction of gauge groups with ranks in a given range, can be statistically predictable. To illustrate our point we show how the uniform measures on simple classes of N=1 quiver gauge theories localize in the vicinity of theories with certain typical structures. Generically, this approach would predict a high energy theory with very many gauge factors, with the high rank factors largely decoupled from the low rank factors if we require asymptotic freedom for the latter.

  4. Landscape Classifications for Landscape Metrics-based Assessment of Urban Heat Island: A Comparative Study

    International Nuclear Information System (INIS)

    Zhao, X F; Deng, L; Wang, H N; Chen, F; Hua, L Z

    2014-01-01

    In recent years, some studies have been carried out on the landscape analysis of urban thermal patterns. With the prevalence of thermal landscape, a key problem has come forth, which is how to classify thermal landscape into thermal patches. Current researches used different methods of thermal landscape classification such as standard deviation method (SD) and R method. To find out the differences, a comparative study was carried out in Xiamen using a 20-year winter time-serial Landsat images. After the retrieval of land surface temperature (LST), the thermal landscape was classified using the two methods separately. Then landscape metrics, 6 at class level and 14 at landscape level, were calculated and analyzed using Fragstats 3.3. We found that: (1) at the class level, all the metrics with SD method were evened and did not show an obvious trend along with the process of urbanization, while the R method could. (2) While at the landscape level, 6 of the 14 metrics remains the similar trends, 5 were different at local turn points of the curve, 3 of them differed completely in the shape of curves. (3) When examined with visual interpretation, SD method tended to exaggerate urban heat island effects than the R method

  5. Perbedaan Asupan Energi, Protein, Zink, dan Perkembangan pada Balita Stunting dan non Stunting

    OpenAIRE

    Adani, Farahiyah Yusni; Nindya, Triska Susila

    2017-01-01

     Background: Stunting is a nutritional problem caused by inadequate nutrition intake for  a long time and/or recurrent infectious diseases. The impacts of stunting are increase mortality,  morbidity,  health costs, decrease cognitive development, motor, and language development.There are nutrients that important to linear growth as energy, protein, and zinc. Objectives: The purpose of this study was to analyze the differences of intake of the energy, protein, Zinc, development in stunting and...

  6. On the development of protein pKa calculation algorithms

    Science.gov (United States)

    Carstensen, Tommy; Farrell, Damien; Huang, Yong; Baker, Nathan A.; Nielsen, Jens Erik

    2011-01-01

    Protein pKa calculation methods are developed partly to provide fast non-experimental estimates of the ionization constants of protein side chains. However, the most significant reason for developing such methods is that a good pKa calculation method is presumed to provide an accurate physical model of protein electrostatics, which can be applied in methods for drug design, protein design and other structure-based energy calculation methods. We explore the validity of this presumption by simulating the development of a pKa calculation method using artificial experimental data derived from a human-defined physical reality. We examine the ability of an RMSD-guided development protocol to retrieve the correct (artificial) physical reality and find that a rugged optimization landscape and a huge parameter space prevent the identification of the correct physical reality. We examine the importance of the training set in developing pKa calculation methods and investigate the effect of experimental noise on our ability to identify the correct physical reality, and find that both effects have a significant and detrimental impact on the physical reality of the optimal model identified. Our findings are of relevance to all structure-based methods for protein energy calculations and simulation, and have large implications for all types of current pKa calculation methods. Our analysis furthermore suggests that careful and extensive validation on many types of experimental data can go some way in making current models more realistic. PMID:21744393

  7. New concept of aging care architecture landscape design based on sustainable development

    Science.gov (United States)

    Xu, Ying

    2017-05-01

    As the aging problem becoming serious in China, Aging care is now one of the top issuer in front of all of us. Lots of private and public aging care architecture and facilities have been built. At present, we only pay attention to the architecture design and interior design scientific, ecological and sustainable design on aged care architecture landscape. Based on the social economy, population resources, mutual coordination and development of the environment, taking the elderly as the special group, this paper follows the principles of the sustainable development, conducts the comprehensive design planning of aged care landscape architecture and makes a deeper understanding and exploration through changing the form of architectural space, ecological landscape planting, new materials and technology, ecological energy utilization.

  8. Ratchet Effects and Domain Wall Energy Landscapes in Amorphous Magnetic Films with 2D Arrays of Asymmetric Holes

    Science.gov (United States)

    Martin, J. I.; Alija, A.; Sobrado, I.; Perez-Junquera, A.; Rodriguez-Rodriguez, G.; Velez, M.; Alameda, J. M.; Marconi, V. I.; Kolton, A. B.; Parrondo, J. M. R.

    2009-03-01

    The driven motion of domain walls in extended magnetic films patterned with 2D arrays of asymmetric holes has been found to be subject to two different crossed ratchet effects [1] which results in an inversion of the sign of domain wall motion rectification as a function of the applied magnetic field. This effect can be understood in terms of the competition between drive, elasticity and asymmetric pinning as revealed by a simple 4̂-model. In order to optimize the asymmetric hole design, the relevant energy landscapes for domain wall motion across the array of asymmetric holes have been calculated by micromagnetic simulations as a function of array geometrical characteristics. The effects of a transverse magnetic field on these two crossed ratchet effects will also be discussed in terms of the decrease in domain wall energy per unit area and of the modifications in the magnetostatic barriers for domain wall pinning at the asymmetric inclusions. Work supported by Spanish MICINN.[1] A. Perez-Junquera et al, Phys. Rev. Lett. 100 (2008) 037203

  9. Provision of protein and energy in relation to measured requirements in intensive care patients

    DEFF Research Database (Denmark)

    Allingstrup, Matilde Jo; Esmailzadeh, Negar; Knudsen, Anne Wilkens

    2012-01-01

    , also when adjusted for baseline prognostic variables (APACHE II, SOFA scores and age). Provision of energy, measured resting energy expenditure or energy and nitrogen balance was not related to mortality. The possible cause-effect relationship is discussed after a more detailed analysis of the initial......BACKGROUND & AIMS: Adequacy of nutritional support in intensive care patients is still a matter of investigation. This study aimed to relate mortality to provision, measured requirements and balances for energy and protein in ICU patients. DESIGN: Prospective observational cohort study of 113 ICU...... part of the admission. CONCLUSION: In these severely ill ICU patients, a higher provision of protein and amino acids was associated with a lower mortality. This was not the case for provision of energy or measured resting energy expenditure or energy or nitrogen balances. The hypothesis that higher...

  10. Landscape of climate finance in France 2011-2014 - 2015 Edition - Executive Summary

    International Nuclear Information System (INIS)

    Hainaut, Hadrien; Morel, Romain; Cochran, Ian

    2015-11-01

    The Landscape of Climate Finance surveys investment in tangible (physical) assets contributing to climate change mitigation and resulting directly or indirectly in greenhouse gas emissions (GHG) emission reductions - generally referred to as climate investments. This total is made up of investments of euro 17.6 bn in energy efficiency, euro 5.1 bn in renewable energy and euro 12 bn for sustainable transport infrastructure. Investments in new nuclear plants and GHG reductions outside of energy consumption (agriculture, forestry, industrial processes, etc.) totaled an estimated euro 1.4 bn. An increase in investment was noted in low-emission new buildings and sustainable transport infrastructure, while investment in renewable energy decreased over the same period. The Landscape of Climate Finance is a comprehensive study of financial flows in favor of climate and the broader energy transition in France. The study maps the flows supporting investments leading to greenhouse gas mitigation across the French economy. The results discussed in the report present trends seen between 2011 and 2014, with a detailed focus on 2013. Findings are contextualized in two ways: first, they are compared with the general characteristics of the financing of the French economy; second, the volumes identified are assessed in comparison to existing projected investment needs to achieve GHG emission reduction targets and energy transition objectives. The final objective of the study is to contribute to the public debate on the role and relevancy of public and private finance in support of climate mitigation. This French Landscape of Climate Finance is based on the aggregation of a large number of often-fragmented sources and estimations. All results reflect explicit methodological choices made by the authors based on existing national and international approaches and should, thus, be understood as orders of magnitude including a varying degree of uncertainty

  11. Land-Sparing Opportunities for Solar Energy Development in Agricultural Landscapes: A Case Study of the Great Central Valley, CA, United States.

    Science.gov (United States)

    Hoffacker, Madison K; Allen, Michael F; Hernandez, Rebecca R

    2017-12-19

    Land-cover change from energy development, including solar energy, presents trade-offs for land used for the production of food and the conservation of ecosystems. Solar energy plays a critical role in contributing to the alternative energy mix to mitigate climate change and meet policy milestones; however, the extent that solar energy development on nonconventional surfaces can mitigate land scarcity is understudied. Here, we evaluate the land sparing potential of solar energy development across four nonconventional land-cover types: the built environment, salt-affected land, contaminated land, and water reservoirs (as floatovoltaics), within the Great Central Valley (CV, CA), a globally significant agricultural region where land for food production, urban development, and conservation collide. Furthermore, we calculate the technical potential (TWh year -1 ) of these land sparing sites and test the degree to which projected electricity needs for the state of California can be met therein. In total, the CV encompasses 15% of CA, 8415 km 2 of which was identified as potentially land-sparing for solar energy development. These areas comprise a capacity-based energy potential of at least 17 348 TWh year -1 for photovoltaic (PV) and 2213 TWh year -1 for concentrating solar power (CSP). Accounting for technology efficiencies, this exceeds California's 2025 projected electricity demands up to 13 and 2 times for PV and CSP, respectively. Our study underscores the potential of strategic renewable energy siting to mitigate environmental trade-offs typically coupled with energy sprawl in agricultural landscapes.

  12. Scoring predictive models using a reduced representation of proteins: model and energy definition.

    Science.gov (United States)

    Fogolari, Federico; Pieri, Lidia; Dovier, Agostino; Bortolussi, Luca; Giugliarelli, Gilberto; Corazza, Alessandra; Esposito, Gennaro; Viglino, Paolo

    2007-03-23

    Reduced representations of proteins have been playing a keyrole in the study of protein folding. Many such models are available, with different representation detail. Although the usefulness of many such models for structural bioinformatics applications has been demonstrated in recent years, there are few intermediate resolution models endowed with an energy model capable, for instance, of detecting native or native-like structures among decoy sets. The aim of the present work is to provide a discrete empirical potential for a reduced protein model termed here PC2CA, because it employs a PseudoCovalent structure with only 2 Centers of interactions per Amino acid, suitable for protein model quality assessment. All protein structures in the set top500H have been converted in reduced form. The distribution of pseudobonds, pseudoangle, pseudodihedrals and distances between centers of interactions have been converted into potentials of mean force. A suitable reference distribution has been defined for non-bonded interactions which takes into account excluded volume effects and protein finite size. The correlation between adjacent main chain pseudodihedrals has been converted in an additional energetic term which is able to account for cooperative effects in secondary structure elements. Local energy surface exploration is performed in order to increase the robustness of the energy function. The model and the energy definition proposed have been tested on all the multiple decoys' sets in the Decoys'R'us database. The energetic model is able to recognize, for almost all sets, native-like structures (RMSD less than 2.0 A). These results and those obtained in the blind CASP7 quality assessment experiment suggest that the model compares well with scoring potentials with finer granularity and could be useful for fast exploration of conformational space. Parameters are available at the url: http://www.dstb.uniud.it/~ffogolari/download/.

  13. The Roles of Structural Order and Intermolecular Interactions in Determining Ionization Energies and Charge-Transfer State Energies in Organic Semiconductors

    KAUST Repository

    Graham, Kenneth

    2016-08-17

    The energy landscape in organic semiconducting materials greatly influences charge and exciton behavior, which are both critical to the operation of organic electronic devices. These energy landscapes can change dramatically depending on the phases of material present, including pure phases of one molecule or polymer and mixed phases exhibiting different degrees of order and composition. In this work, ultraviolet photoelectron spectroscopy measurements of ionization energies (IEs) and external quantum efficiency measurements of charge-transfer (CT) state energies (ECT) are applied to molecular photovoltaic material systems to characterize energy landscapes. The results show that IEs and ECT values are highly dependent on structural order and phase composition. In the sexithiophene:C60 system both the IEs of sexithiophene and C60 shift by over 0.4 eV while ECT shifts by 0.5 eV depending on molecular composition. By contrast, in the rubrene:C60 system the IE of rubrene and C60 vary by ≤0.11 eV and ECT varies by ≤0.04 eV as the material composition varies. These results suggest that energy landscapes can exist whereby the binding energies of the CT states are overcome by energy offsets between charges in CT states in mixed regions and free charges in pure phases. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Vibrational energy flow through the green fluorescent protein-water interface: communication maps and thermal boundary conductance.

    Science.gov (United States)

    Xu, Yao; Leitner, David M

    2014-07-17

    We calculate communication maps for green fluorescent protein (GFP) to elucidate energy transfer pathways between the chromophore and other parts of the protein in the ground and excited state. The approach locates energy transport channels from the chromophore to remote regions of the protein via residues and water molecules that hydrogen bond to the chromophore. We calculate the thermal boundary conductance between GFP and water over a wide range of temperature and find that the interface between the protein and the cluster of water molecules in the β-barrel poses negligible resistance to thermal flow, consistent with facile vibrational energy transfer from the chromophore to the β-barrel waters observed in the communication maps.

  15. Municipal mobilisation of materials for the landscape conservation; Kommunale Mobilisierung von Landschaftspflegematerial

    Energy Technology Data Exchange (ETDEWEB)

    Bruening, Arnd; Kottbusch, Bastian; Haensch, David; Hartz, Franziska [Bruening-Megawatt GmbH, Fischerhude (Germany)

    2013-10-01

    Since summer 2012, Bruening-Megawatt GmbH has been making more intensive efforts in coordinating community mobilisation of landscape management material. Such material is an important factor in maintaining full supply to the 6 biomass power (and thermal energy) plants, under contract to Bayernfonds BestEnergy 1 GmbH and Co. KG (BBE). These plants, located at Niesky, Leipzig, Bad Arolsen, Steinau an der Strasse, Langelsheim and Rieste, each have an output of 5 MW/h and consume approx. 200 tonnes of solid fuel every day. Already a proportion amounting to 1/10 of this requirement (approx. 25 tonnes, or 1 truck-trailer load) originates from community projects during the landscape maintenance months. For the period from October to February this yields a total of approximately 3,750 tonnes per power plant. Summed up over all 6 BBE plants, Bruning-Megawatt GmbH thus supplies approximately 22,500 tonnes of landscape management material originating from cooperation with municipalities and towns, to these biomass power (and thermal energy) plants. This amount is accordingly reduced during the summer months. These projects prove to be financially practical for the municipalities. They do not need to pay third parties for the disposal of branch cuttings and hedgerow trimmings, and Bruening-Megawatt GmbH pays them a fixed amount per tonne, depending on the quality of the clippings. (orig.)

  16. One-dimensional arrays of oscillators: Energy localization in thermal equilibrium

    International Nuclear Information System (INIS)

    Reigada, R.; Romero, A.H.; Sarmiento, A.; Lindenberg, K.

    1999-01-01

    All systems in thermal equilibrium exhibit a spatially variable energy landscape due to thermal fluctuations. Thus at any instant there is naturally a thermodynamically driven localization of energy in parts of the system relative to other parts of the system. The specific characteristics of the spatial landscape such as, for example, the energy variance, depend on the thermodynamic properties of the system and vary from one system to another. The temporal persistence of a given energy landscape, that is, the way in which energy fluctuations (high or low) decay toward the thermal mean, depends on the dynamical features of the system. We discuss the spatial and temporal characteristics of spontaneous energy localization in 1D anharmonic chains in thermal equilibrium. copyright 1999 American Institute of Physics

  17. Management of protein-energy wasting in non-dialysis-dependent chronic kidney disease: reconciling low protein intake with nutritional therapy.

    Science.gov (United States)

    Kovesdy, Csaba P; Kopple, Joel D; Kalantar-Zadeh, Kamyar

    2013-06-01

    Protein-energy wasting (PEW), characterized by a decline in body protein mass and energy reserves, including muscle and fat wasting and visceral protein pool contraction, is an underappreciated condition in early to moderate stages of chronic kidney disease (CKD) and a strong predictor of adverse outcomes. The prevalence of PEW in early to moderate CKD is ≥20-25% and increases as CKD progresses, in part because of activation of proinflammatory cytokines combined with superimposed hypercatabolic states and declines in appetite. This anorexia leads to inadequate protein and energy intake, which may be reinforced by prescribed dietary restrictions and inadequate monitoring of the patient's nutritional status. Worsening uremia also renders CKD patients vulnerable to potentially deleterious effects of uncontrolled diets, including higher phosphorus and potassium burden. Uremic metabolites, some of which are anorexigenic and many of which are products of protein metabolism, can exert harmful effects, ranging from oxidative stress to endothelial dysfunction, nitric oxide disarrays, renal interstitial fibrosis, sarcopenia, and worsening proteinuria and kidney function. Given such complex pathways, nutritional interventions in CKD, when applied in concert with nonnutritional therapeutic approaches, encompass an array of strategies (such as dietary restrictions and supplementations) aimed at optimizing both patients' biochemical variables and their clinical outcomes. The applicability of many nutritional interventions and their effects on outcomes in patients with CKD with PEW has not been well studied. This article reviews the definitions and pathophysiology of PEW in patients with non-dialysis-dependent CKD, examines the current indications for various dietary modification strategies in patients with CKD (eg, manufactured protein-based supplements, amino acids and their keto acid or hydroxyacid analogues), discusses the rationale behind their potential use in patients

  18. Landscape Ecology and problems of European cultural landscapes

    DEFF Research Database (Denmark)

    Brandt, Jesper

    2011-01-01

    by practical problems of European cultural – especial agricultural – landscapes since the rise of the environmental movement. Central themes have been the consequences of technological and structural changes within European agriculture for the landscape and the development of habitats and dispersal...... Problemstellungen basieren auf multifunktionalen Nutzungskonzepten ruraler Landschaften, besonders im Hinblick auf Suburbanisierungsprozesse. Eine Anzahl untereinander vergleichbarer Projekte, mit parallelen bis ähnlichen Ausprägungen innerhalb Dänemarks und weiteerer europäischer Länder, werden exemplarisch...

  19. Higgs and superparticle mass predictions from the landscape

    Science.gov (United States)

    Baer, Howard; Barger, Vernon; Serce, Hasan; Sinha, Kuver

    2018-03-01

    Predictions for the scale of SUSY breaking from the string landscape go back at least a decade to the work of Denef and Douglas on the statistics of flux vacua. The assumption that an assortment of SUSY breaking F and D terms are present in the hidden sector, and their values are uniformly distributed in the landscape of D = 4, N = 1 effective supergravity models, leads to the expectation that the landscape pulls towards large values of soft terms favored by a power law behavior P( m soft) ˜ m soft n . On the other hand, similar to Weinberg's prediction of the cosmological constant, one can assume an anthropic selection of weak scales not too far from the measured value characterized by m W,Z,h ˜ 100 GeV. Working within a fertile patch of gravity-mediated low energy effective theories where the superpotential μ term is ≪ m 3/2, as occurs in models such as radiative breaking of Peccei-Quinn symmetry, this biases statistical distributions on the landscape by a cutoff on the parameter ΔEW, which measures fine-tuning in the m Z - μ mass relation. The combined effect of statistical and anthropic pulls turns out to favor low energy phenomenology that is more or less agnostic to UV physics. While a uniform selection n = 0 of soft terms produces too low a value for m h , taking n = 1 and 2 produce most probabilistically m h ˜ 125 GeV for negative trilinear terms. For n ≥ 1, there is a pull towards split generations with {m}_{\\tilde{q},\\tilde{ℓ}}(1,2)˜ 10-30 TeV whilst {m}_{{\\tilde{t}}_1}˜ 1-2 TeV . The most probable gluino mass comes in at ˜ 3 - 4 TeV — apparently beyond the reach of HL-LHC (although the required quasi-degenerate higgsinos should still be within reach). We comment on consequences for SUSY collider and dark matter searches.

  20. Vectorial loading of processive motor proteins: implementing a landscape picture

    International Nuclear Information System (INIS)

    Kim, Young C; Fisher, Michael E

    2005-01-01

    Individual processive molecular motors, of which conventional kinesin is the most studied quantitatively, move along polar molecular tracks and, by exerting a force F = (F x ,F y ,F z ) on a tether, drag cellular cargoes, in vivo, or spherical beads, in vitro, taking up to hundreds of nanometre-scale steps. From observations of velocities and the dispersion of displacements with time, under measured forces and controlled fuel supply (typically ATP), one may hope to obtain insight into the molecular motions undergone in the individual steps. In the simplest situation, the load force F may be regarded as a scalar resisting force, F x z >0, while more recently Block and co-workers (2002 Biophys. J. 83 491, 2003 Proc. Natl Acad. Sci. USA 100 2351) and Carter and Cross (2005 Nature 435 308) have studied assisting (or reverse) loads, F x >0, and also sideways (or transverse) loads F y ≠ 0. We extend previous mechanochemical kinetic models by explicitly implementing a free-energy landscape picture in order to allow for the full vectorial nature of the force F transmitted by the tether. The load-dependence of the various forward and reverse transition rates is embodied in load distribution vectors, θ j + and θ j - , which relate to substeps of the motor, and in next order, in compliance matrices η j + and η j - . The approach is applied specifically to discuss the experiments of Howard and co-workers (1996 Biophys.?J. 70 418) in which the buckling of partially clamped microtubules was measured under the action of bound kinesin molecules which induced determined perpendicular loads. But in the normal single-bead assay it also proves imperative to allow for F z >0: the appropriate analysis for kinesin, suggesting that the motor 'crouches' on binding ATP prior to stepping, is sketched. It yields an expression for the velocity, V (F x ,F z ;[ATP]), needed to address the buckling experiments