Equilibrium time correlation functions and the dynamics of fluctuations

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

Luban, Marshall; Luscombe, James H.

1999-12-01

Equilibrium time correlation functions are of great importance because they probe the equilibrium dynamical response to external perturbations. We discuss the properties of time correlation functions for several systems that are simple enough to illustrate the calculational steps involved. The discussion underscores the need for avoiding language which misleadingly suggests that thermal equilibrium is associated with a quiescent or moribund state of the system. (c) 1999 American Association of Physics Teachers.

Mining dynamic noteworthy functions in software execution sequences.

PubMed

Zhang, Bing; Huang, Guoyan; Wang, Yuqian; He, Haitao; Ren, Jiadong

2017-01-01

As the quality of crucial entities can directly affect that of software, their identification and protection become an important premise for effective software development, management, maintenance and testing, which thus contribute to improving the software quality and its attack-defending ability. Most analysis and evaluation on important entities like codes-based static structure analysis are on the destruction of the actual software running. In this paper, from the perspective of software execution process, we proposed an approach to mine dynamic noteworthy functions (DNFM)in software execution sequences. First, according to software decompiling and tracking stack changes, the execution traces composed of a series of function addresses were acquired. Then these traces were modeled as execution sequences and then simplified so as to get simplified sequences (SFS), followed by the extraction of patterns through pattern extraction (PE) algorithm from SFS. After that, evaluating indicators inner-importance and inter-importance were designed to measure the noteworthiness of functions in DNFM algorithm. Finally, these functions were sorted by their noteworthiness. Comparison and contrast were conducted on the experiment results from two traditional complex network-based node mining methods, namely PageRank and DegreeRank. The results show that the DNFM method can mine noteworthy functions in software effectively and precisely.

Understanding subcellular function on the nanometer scale in real time: Single-molecule imaging in living bacteria

NASA Astrophysics Data System (ADS)

Biteen, Julie

It has long been recognized that microorganisms play a central role in our lives. By beating the diffraction limit that restricts traditional light microscopy, single-molecule fluorescence imaging is a precise, noninvasive way to sensitively probe position and dynamics, even in living cells. We are pioneering this super-resolution imaging method for unraveling important biological processes in live bacteria, and I will discuss how we infer function from subcellular dynamics (Tuson and Biteen, Analytical Chemistry 2015). In particular, we have understood the mechanism of membrane-bound transcription regulation in the pathogenic Vibrio cholerae, revealed an intimate and dynamic coupling between DNA mismatch recognition and DNA replication, and measured starch utilization in an important member of the human gut microbiome.

Dynamic New World: Refining Our View of Protein Structure, Function and Evolution

PubMed Central

Mannige, Ranjan V.

2014-01-01

Proteins are crucial to the functioning of all lifeforms. Traditional understanding posits that a single protein occupies a single structure (“fold”), which performs a single function. This view is radically challenged with the recognition that high structural dynamism—the capacity to be extra “floppy”—is more prevalent in functional proteins than previously assumed. As reviewed here, this dynamic take on proteins affects our understanding of protein “structure”, function, and evolution, and even gives us a glimpse into protein origination. Specifically, this review will discuss historical developments concerning protein structure, and important new relationships between dynamism and aspects of protein sequence, structure, binding modes, binding promiscuity, evolvability, and origination. Along the way, suggestions will be provided for how key parts of textbook definitions—that so far have excluded membership to intrinsically disordered proteins (IDPs)—could be modified to accommodate our more dynamic understanding of proteins. PMID:28250374

Importance of curvature evaluation scale for predictive simulations of dynamic gas-liquid interfaces

NASA Astrophysics Data System (ADS)

Owkes, Mark; Cauble, Eric; Senecal, Jacob; Currie, Robert A.

2018-07-01

The effect of the scale used to compute the interfacial curvature on the prediction of dynamic gas-liquid interfaces is investigated. A new interface curvature calculation methodology referred to herein as the Adjustable Curvature Evaluation Scale (ACES) is proposed. ACES leverages a weighted least squares regression to fit a polynomial through points computed on the volume-of-fluid representation of the gas-liquid interface. The interface curvature is evaluated from this polynomial. Varying the least squares weight with distance from the location where the curvature is being computed, adjusts the scale the curvature is evaluated on. ACES is verified using canonical static test cases and compared against second- and fourth-order height function methods. Simulations of dynamic interfaces, including a standing wave and oscillating droplet, are performed to assess the impact of the curvature evaluation scale for predicting interface motions. ACES and the height function methods are combined with two different unsplit geometric volume-of-fluid (VoF) schemes that define the interface on meshes with different levels of refinement. We find that the results depend significantly on curvature evaluation scale. Particularly, the ACES scheme with a properly chosen weight function is accurate, but fails when the scale is too small or large. Surprisingly, the second-order height function method is more accurate than the fourth-order variant for the dynamic tests even though the fourth-order method performs better for static interfaces. Comparing the curvature evaluation scale of the second- and fourth-order height function methods, we find the second-order method is closer to the optimum scale identified with ACES. This result suggests that the curvature scale is driving the accuracy of the dynamics. This work highlights the importance of studying numerical methods with realistic (dynamic) test cases and that the interactions of the various discretizations is as important as the accuracy of one part of the discretization.

Cognitive Flexibility through Metastable Neural Dynamics Is Disrupted by Damage to the Structural Connectome.

PubMed

Hellyer, Peter J; Scott, Gregory; Shanahan, Murray; Sharp, David J; Leech, Robert

2015-06-17

Current theory proposes that healthy neural dynamics operate in a metastable regime, where brain regions interact to simultaneously maximize integration and segregation. Metastability may confer important behavioral properties, such as cognitive flexibility. It is increasingly recognized that neural dynamics are constrained by the underlying structural connections between brain regions. An important challenge is, therefore, to relate structural connectivity, neural dynamics, and behavior. Traumatic brain injury (TBI) is a pre-eminent structural disconnection disorder whereby traumatic axonal injury damages large-scale connectivity, producing characteristic cognitive impairments, including slowed information processing speed and reduced cognitive flexibility, that may be a result of disrupted metastable dynamics. Therefore, TBI provides an experimental and theoretical model to examine how metastable dynamics relate to structural connectivity and cognition. Here, we use complementary empirical and computational approaches to investigate how metastability arises from the healthy structural connectome and relates to cognitive performance. We found reduced metastability in large-scale neural dynamics after TBI, measured with resting-state functional MRI. This reduction in metastability was associated with damage to the connectome, measured using diffusion MRI. Furthermore, decreased metastability was associated with reduced cognitive flexibility and information processing. A computational model, defined by empirically derived connectivity data, demonstrates how behaviorally relevant changes in neural dynamics result from structural disconnection. Our findings suggest how metastable dynamics are important for normal brain function and contingent on the structure of the human connectome. Copyright © 2015 the authors 0270-6474/15/359050-14$15.00/0.

Molecular dynamics simulations and structure-based network analysis reveal structural and functional aspects of G-protein coupled receptor dimer interactions.

PubMed

Baltoumas, Fotis A; Theodoropoulou, Margarita C; Hamodrakas, Stavros J

2016-06-01

A significant amount of experimental evidence suggests that G-protein coupled receptors (GPCRs) do not act exclusively as monomers but also form biologically relevant dimers and oligomers. However, the structural determinants, stoichiometry and functional importance of GPCR oligomerization remain topics of intense speculation. In this study we attempted to evaluate the nature and dynamics of GPCR oligomeric interactions. A representative set of GPCR homodimers were studied through Coarse-Grained Molecular Dynamics simulations, combined with interface analysis and concepts from network theory for the construction and analysis of dynamic structural networks. Our results highlight important structural determinants that seem to govern receptor dimer interactions. A conserved dynamic behavior was observed among different GPCRs, including receptors belonging in different GPCR classes. Specific GPCR regions were highlighted as the core of the interfaces. Finally, correlations of motion were observed between parts of the dimer interface and GPCR segments participating in ligand binding and receptor activation, suggesting the existence of mechanisms through which dimer formation may affect GPCR function. The results of this study can be used to drive experiments aimed at exploring GPCR oligomerization, as well as in the study of transmembrane protein-protein interactions in general.

Molecular dynamics simulations and structure-based network analysis reveal structural and functional aspects of G-protein coupled receptor dimer interactions

NASA Astrophysics Data System (ADS)

Baltoumas, Fotis A.; Theodoropoulou, Margarita C.; Hamodrakas, Stavros J.

2016-06-01

A significant amount of experimental evidence suggests that G-protein coupled receptors (GPCRs) do not act exclusively as monomers but also form biologically relevant dimers and oligomers. However, the structural determinants, stoichiometry and functional importance of GPCR oligomerization remain topics of intense speculation. In this study we attempted to evaluate the nature and dynamics of GPCR oligomeric interactions. A representative set of GPCR homodimers were studied through Coarse-Grained Molecular Dynamics simulations, combined with interface analysis and concepts from network theory for the construction and analysis of dynamic structural networks. Our results highlight important structural determinants that seem to govern receptor dimer interactions. A conserved dynamic behavior was observed among different GPCRs, including receptors belonging in different GPCR classes. Specific GPCR regions were highlighted as the core of the interfaces. Finally, correlations of motion were observed between parts of the dimer interface and GPCR segments participating in ligand binding and receptor activation, suggesting the existence of mechanisms through which dimer formation may affect GPCR function. The results of this study can be used to drive experiments aimed at exploring GPCR oligomerization, as well as in the study of transmembrane protein-protein interactions in general.

Dynamics of Female Pelvic Floor Function Using Urodynamics, Ultrasound and Magnetic Resonance Imaging (MRI)

PubMed Central

Constantinou, Christos E.

2009-01-01

In this review the diagnostic potential of evaluating female pelvic floor muscle (PFM)) function using magnetic and ultrasound imaging in the context of urodynamic observations is considered in terms of determining the mechanisms of urinary continence. A new approach is used to consider the dynamics of PFM activity by introducing new parameters derived from imaging. Novel image processing techniques are applied to illustrate the static anatomy and dynamics PFM function of stress incontinent women pre and post operatively as compared to asymptomatic subjects. Function was evaluated from the dynamics of organ displacement produced during voluntary and reflex activation. Technical innovations include the use of ultrasound analysis of movement of structures during maneuvers that are associated with external stimuli. Enabling this approach is the development of criteria and fresh and unique parameters that define the kinematics of PFM function. Principal among these parameters, are displacement, velocity, acceleration and the trajectory of pelvic floor landmarks. To accomplish this objective, movement detection, including motion tracking algorithms and segmentation algorithms were developed to derive new parameters of trajectory, displacement, velocity and acceleration, and strain of pelvic structures during different maneuvers. Results highlight the importance of timing the movement and deformation to fast and stressful maneuvers, which are important for understanding the neuromuscular control and function of PFM. Furthermore, observations suggest that timing of responses is a significant factor separating the continent from the incontinent subjects. PMID:19303690

Molecular Dynamics Information Improves cis-Peptide-Based Function Annotation of Proteins.

PubMed

Das, Sreetama; Bhadra, Pratiti; Ramakumar, Suryanarayanarao; Pal, Debnath

2017-08-04

cis-Peptide bonds, whose occurrence in proteins is rare but evolutionarily conserved, are implicated to play an important role in protein function. This has led to their previous use in a homology-independent, fragment-match-based protein function annotation method. However, proteins are not static molecules; dynamics is integral to their activity. This is nicely epitomized by the geometric isomerization of cis-peptide to trans form for molecular activity. Hence we have incorporated both static (cis-peptide) and dynamics information to improve the prediction of protein molecular function. Our results show that cis-peptide information alone cannot detect functional matches in cases where cis-trans isomerization exists but 3D coordinates have been obtained for only the trans isomer or when the cis-peptide bond is incorrectly assigned as trans. On the contrary, use of dynamics information alone includes false-positive matches for cases where fragments with similar secondary structure show similar dynamics, but the proteins do not share a common function. Combining the two methods reduces errors while detecting the true matches, thereby enhancing the utility of our method in function annotation. A combined approach, therefore, opens up new avenues of improving existing automated function annotation methodologies.

‘Activity-silent’ working memory in prefrontal cortex: a dynamic coding framework

PubMed Central

Stokes, Mark G.

2015-01-01

Working memory (WM) provides the functional backbone to high-level cognition. Maintenance in WM is often assumed to depend on the stationary persistence of neural activity patterns that represent memory content. However, accumulating evidence suggests that persistent delay activity does not always accompany WM maintenance but instead seems to wax and wane as a function of the current task relevance of memoranda. Furthermore, new methods for measuring and analysing population-level patterns show that activity states are highly dynamic. At first glance, these dynamics seem at odds with the very nature of WM. How can we keep a stable thought in mind while brain activity is constantly changing? This review considers how neural dynamics might be functionally important for WM maintenance. PMID:26051384

Morphological dynamics of mitochondria--a special emphasis on cardiac muscle cells.

PubMed

Hom, Jennifer; Sheu, Shey-Shing

2009-06-01

Mitochondria play a critical role in cellular energy metabolism, Ca(2+) homeostasis, reactive oxygen species generation, apoptosis, aging, and development. Many recent publications have shown that a continuous balance of fusion and fission of these organelles is important in maintaining their proper function. Therefore, there is a steep correlation between the form and function of mitochondria. Many major proteins involved in mitochondrial fusion and fission have been identified in different cell types, including heart. However, the functional role of mitochondrial dynamics in the heart remains, for the most part, unexplored. In this review we will cover the recent field of mitochondrial dynamics and its physiological and pathological implications, with a particular emphasis on the experimental and theoretical basis of mitochondrial dynamics in the heart.

Parameter and Structure Inference for Nonlinear Dynamical Systems

NASA Technical Reports Server (NTRS)

Morris, Robin D.; Smelyanskiy, Vadim N.; Millonas, Mark

2006-01-01

A great many systems can be modeled in the non-linear dynamical systems framework, as x = f(x) + xi(t), where f() is the potential function for the system, and xi is the excitation noise. Modeling the potential using a set of basis functions, we derive the posterior for the basis coefficients. A more challenging problem is to determine the set of basis functions that are required to model a particular system. We show that using the Bayesian Information Criteria (BIC) to rank models, and the beam search technique, that we can accurately determine the structure of simple non-linear dynamical system models, and the structure of the coupling between non-linear dynamical systems where the individual systems are known. This last case has important ecological applications.

The Role of Protein Loops and Linkers in Conformational Dynamics and Allostery.

PubMed

Papaleo, Elena; Saladino, Giorgio; Lambrughi, Matteo; Lindorff-Larsen, Kresten; Gervasio, Francesco Luigi; Nussinov, Ruth

2016-06-08

Proteins are dynamic entities that undergo a plethora of conformational changes that may take place on a wide range of time scales. These changes can be as small as the rotation of one or a few side-chain dihedral angles or involve concerted motions in larger portions of the three-dimensional structure; both kinds of motions can be important for biological function and allostery. It is becoming increasingly evident that "connector regions" are important components of the dynamic personality of protein structures. These regions may be either disordered loops, i.e., poorly structured regions connecting secondary structural elements, or linkers that connect entire protein domains. Experimental and computational studies have, however, revealed that these regions are not mere connectors, and their role in allostery and conformational changes has been emerging in the last few decades. Here we provide a detailed overview of the structural properties and classification of loops and linkers, as well as a discussion of the main computational methods employed to investigate their function and dynamical properties. We also describe their importance for protein dynamics and allostery using as examples key proteins in cellular biology and human diseases such as kinases, ubiquitinating enzymes, and transcription factors.

F-BAR family proteins, emerging regulators for cell membrane dynamic changes-from structure to human diseases.

PubMed

Liu, Suxuan; Xiong, Xinyu; Zhao, Xianxian; Yang, Xiaofeng; Wang, Hong

2015-05-09

Eukaryotic cell membrane dynamics change in curvature during physiological and pathological processes. In the past ten years, a novel protein family, Fes/CIP4 homology-Bin/Amphiphysin/Rvs (F-BAR) domain proteins, has been identified to be the most important coordinators in membrane curvature regulation. The F-BAR domain family is a member of the Bin/Amphiphysin/Rvs (BAR) domain superfamily that is associated with dynamic changes in cell membrane. However, the molecular basis in membrane structure regulation and the biological functions of F-BAR protein are unclear. The pathophysiological role of F-BAR protein is unknown. This review summarizes the current understanding of structure and function in the BAR domain superfamily, classifies F-BAR family proteins into nine subfamilies based on domain structure, and characterizes F-BAR protein structure, domain interaction, and functional relevance. In general, F-BAR protein binds to cell membrane via F-BAR domain association with membrane phospholipids and initiates membrane curvature and scission via Src homology-3 (SH3) domain interaction with its partner proteins. This process causes membrane dynamic changes and leads to seven important cellular biological functions, which include endocytosis, phagocytosis, filopodium, lamellipodium, cytokinesis, adhesion, and podosome formation, via distinct signaling pathways determined by specific domain-binding partners. These cellular functions play important roles in many physiological and pathophysiological processes. We further summarize F-BAR protein expression and mutation changes observed in various diseases and developmental disorders. Considering the structure feature and functional implication of F-BAR proteins, we anticipate that F-BAR proteins modulate physiological and pathophysiological processes via transferring extracellular materials, regulating cell trafficking and mobility, presenting antigens, mediating extracellular matrix degradation, and transmitting signaling for cell proliferation.

Sediment-stabilizing and Destabilizing Ecoengineering Species from River to Estuary: the Case of the Scheldt System

NASA Astrophysics Data System (ADS)

Selakovic, S.; Cozzoli, F.; Leuven, J.; Van Braeckel, A.; Speybroeck, J.; Kleinhans, M. G.; Bouma, T.

2017-12-01

Interactions between organisms and landscape forming processes play an important role in evolution of coastal landscapes. In particular, biota has a strong potential to interact with important geomorphological processes such as sediment dynamics. Although many studies worked towards quantifying the impact of different species groups on sediment dynamics, information has been gathered on an ad hoc base. Depending on species' traits and distribution, functional groups of ecoengineering species may have differential effects on sediment deposition and erosion. We hypothesize that the spatial distributions of sediment-stabilizing and destabilizing species across the channel and along the whole salinity gradient of an estuary partly determine the planform shape and channel-shoal morphology of estuaries. To test this hypothesis, we analyze vegetation and macrobenthic data taking the Scheldt river-estuarine continuum as model ecosystem. We identify species traits with important effects on sediment dynamics and use them to form functional groups. By using linearized mixed modelling, we are able to accurately describe the distributions of the different functional groups. We observe a clear distinction of dominant ecosystem engineering functional groups and their potential effects on the sediment in the river-estuarine continuum. The first results of longitudinal cross section show the highest effects of stabilizing plant species in riverine and sediment bioturbators in weak polyhaline part of continuum. The distribution of functional groups in transverse cross sections shows dominant stabilizing effect in supratidal zone compared to dominant destabilizing effect in the lower intertidal zone. This analysis offers a new and more general conceptualization of distributions of sediment stabilizing and destabilizing functional groups and their potential impacts on sediment dynamics, shoal patterns, and planform shapes in river-estuarine continuum. We intend to test this in future modelling and experiments.

Combining protein sequence, structure, and dynamics: A novel approach for functional evolution analysis of PAS domain superfamily.

PubMed

Dong, Zheng; Zhou, Hongyu; Tao, Peng

2018-02-01

PAS domains are widespread in archaea, bacteria, and eukaryota, and play important roles in various functions. In this study, we aim to explore functional evolutionary relationship among proteins in the PAS domain superfamily in view of the sequence-structure-dynamics-function relationship. We collected protein sequences and crystal structure data from RCSB Protein Data Bank of the PAS domain superfamily belonging to three biological functions (nucleotide binding, photoreceptor activity, and transferase activity). Protein sequences were aligned and then used to select sequence-conserved residues and build phylogenetic tree. Three-dimensional structure alignment was also applied to obtain structure-conserved residues. The protein dynamics were analyzed using elastic network model (ENM) and validated by molecular dynamics (MD) simulation. The result showed that the proteins with same function could be grouped by sequence similarity, and proteins in different functional groups displayed statistically significant difference in their vibrational patterns. Interestingly, in all three functional groups, conserved amino acid residues identified by sequence and structure conservation analysis generally have a lower fluctuation than other residues. In addition, the fluctuation of conserved residues in each biological function group was strongly correlated with the corresponding biological function. This research suggested a direct connection in which the protein sequences were related to various functions through structural dynamics. This is a new attempt to delineate functional evolution of proteins using the integrated information of sequence, structure, and dynamics. © 2017 The Protein Society.

Detecting brain dynamics during resting state: a tensor based evolutionary clustering approach

NASA Astrophysics Data System (ADS)

Al-sharoa, Esraa; Al-khassaweneh, Mahmood; Aviyente, Selin

2017-08-01

Human brain is a complex network with connections across different regions. Understanding the functional connectivity (FC) of the brain is important both during resting state and task; as disruptions in connectivity patterns are indicators of different psychopathological and neurological diseases. In this work, we study the resting state functional connectivity networks (FCNs) of the brain from fMRI BOLD signals. Recent studies have shown that FCNs are dynamic even during resting state and understanding the temporal dynamics of FCNs is important for differentiating between different conditions. Therefore, it is important to develop algorithms to track the dynamic formation and dissociation of FCNs of the brain during resting state. In this paper, we propose a two step tensor based community detection algorithm to identify and track the brain network community structure across time. First, we introduce an information-theoretic function to reduce the dynamic FCN and identify the time points that are similar topologically to combine them into a tensor. These time points will be used to identify the different FC states. Second, a tensor based spectral clustering approach is developed to identify the community structure of the constructed tensors. The proposed algorithm applies Tucker decomposition to the constructed tensors and extract the orthogonal factor matrices along the connectivity mode to determine the common subspace within each FC state. The detected community structure is summarized and described as FC states. The results illustrate the dynamic structure of resting state networks (RSNs), including the default mode network, somatomotor network, subcortical network and visual network.

Dynamic Structure Factor: An Introduction

NASA Astrophysics Data System (ADS)

Sturm, K.

1993-02-01

The doubly differential cross-section for weak inelastic scattering of waves or particles by manybody systems is derived in Born approximation and expressed in terms of the dynamic structure factor according to van Hove. The application of this very general scheme to scattering of neutrons, x-rays and high-energy electrons is discussed briefly. The dynamic structure factor, which is the space and time Fourier transform of the density-density correlation function, is a property of the many-body system independent of the external probe and carries information on the excitation spectrum of the system. The relation of the electronic structure factor to the density-density response function defined in linear-response theory is shown using the fluctuation-dissipation theorem. This is important for calculations, since the response function can be calculated approximately from the independent-particle response function in self-consistent field approximations, such as the random-phase approximation or the local-density approximation of the density functional theory. Since the density-density response function also determines the dielectric function, the dynamic structure can be expressed by the dielectric function.

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

Busch, Albert; Kiel, Tilman; Heupel, Wolfgang-M.

Lamins, which form the nuclear lamina, not only constitute an important determinant of nuclear architecture, but additionally play essential roles in many nuclear functions. Mutations in A-type lamins cause a wide range of human genetic disorders (laminopathies). The importance of lamin A (LaA) in the spatial arrangement of nuclear pore complexes (NPCs) prompted us to study the role of LaA mutants in nuclear protein transport. Two mutants, causing prenatal skin disease restrictive dermopathy (RD) and the premature aging disease Hutchinson Gilford progeria syndrome, were used for expression in HeLa cells to investigate their impact on the subcellular localization of NPC-associatedmore » proteins and nuclear protein import. Furthermore, dynamics of the LaA mutants within the nuclear lamina were studied. We observed affected localization of NPC-associated proteins, diminished lamina dynamics for both LaA mutants and reduced nuclear import of representative cargo molecules. Intriguingly, both LaA mutants displayed similar effects on nuclear morphology and functions, despite their differences in disease severity. Reduced nuclear protein import was also seen in RD fibroblasts and impaired lamina dynamics for the nucleoporin Nup153. Our data thus represent the first study of a direct link between LaA mutant expression and reduced nuclear protein import.« less

The dynamic regulation of NAD metabolism in mitochondria

PubMed Central

Stein, Liana Roberts; Imai, Shin-ichiro

2012-01-01

Mitochondria are intracellular powerhouses that produce ATP and carry out diverse functions for cellular energy metabolism. While the maintenance of an optimal NAD/NADH ratio is essential for mitochondrial function, it has recently become apparent that the maintenance of the mitochondrial NAD pool also has critical importance. The biosynthesis, transport, and catabolism of NAD and its key intermediates play an important role in the regulation of NAD-consuming mediators, such as sirtuins, poly-ADP-ribose polymerases, and CD38/157 ectoenzymes, in intra- and extracellular compartments. Mitochondrial NAD biosynthesis is also modulated in response to nutritional and environmental stimuli. In this article, we discuss this dynamic regulation of NAD metabolism in mitochondria to shed light on the intimate connection between NAD and mitochondrial function. PMID:22819213

Cholinergic modulation of cognitive processing: insights drawn from computational models

PubMed Central

Newman, Ehren L.; Gupta, Kishan; Climer, Jason R.; Monaghan, Caitlin K.; Hasselmo, Michael E.

2012-01-01

Acetylcholine plays an important role in cognitive function, as shown by pharmacological manipulations that impact working memory, attention, episodic memory, and spatial memory function. Acetylcholine also shows striking modulatory influences on the cellular physiology of hippocampal and cortical neurons. Modeling of neural circuits provides a framework for understanding how the cognitive functions may arise from the influence of acetylcholine on neural and network dynamics. We review the influences of cholinergic manipulations on behavioral performance in working memory, attention, episodic memory, and spatial memory tasks, the physiological effects of acetylcholine on neural and circuit dynamics, and the computational models that provide insight into the functional relationships between the physiology and behavior. Specifically, we discuss the important role of acetylcholine in governing mechanisms of active maintenance in working memory tasks and in regulating network dynamics important for effective processing of stimuli in attention and episodic memory tasks. We also propose that theta rhythm plays a crucial role as an intermediary between the physiological influences of acetylcholine and behavior in episodic and spatial memory tasks. We conclude with a synthesis of the existing modeling work and highlight future directions that are likely to be rewarding given the existing state of the literature for both empiricists and modelers. PMID:22707936

Morphological Dynamics of Mitochondria – A Special Emphasis on Cardiac Muscle Cells

PubMed Central

Hom, Jennifer; Sheu, Shey-Shing

2010-01-01

Mitochondria play a critical role in cellular energy metabolism, Ca2+ homeostasis, reactive oxygen species generation, apoptosis, aging, and development. Many recent publications have shown that a continuous balance of fusion and fission of these organelles is important in maintaining their proper function. Therefore, there is a steep correlation between the form and function of mitochondria. Many major proteins involved in mitochondrial fusion and fission have been identified in different cell types, including heart. However, the functional role of mitochondrial dynamics in the heart remains, for the most part, unexplored. In this review we will cover the recent field of mitochondrial dynamics and its physiological and pathological implications, with a particular emphasis on the experimental and theoretical basis of mitochondrial dynamics in the heart. PMID:19281816

Mining dynamic noteworthy functions in software execution sequences

PubMed Central

Huang, Guoyan; Wang, Yuqian; He, Haitao; Ren, Jiadong

2017-01-01

As the quality of crucial entities can directly affect that of software, their identification and protection become an important premise for effective software development, management, maintenance and testing, which thus contribute to improving the software quality and its attack-defending ability. Most analysis and evaluation on important entities like codes-based static structure analysis are on the destruction of the actual software running. In this paper, from the perspective of software execution process, we proposed an approach to mine dynamic noteworthy functions (DNFM)in software execution sequences. First, according to software decompiling and tracking stack changes, the execution traces composed of a series of function addresses were acquired. Then these traces were modeled as execution sequences and then simplified so as to get simplified sequences (SFS), followed by the extraction of patterns through pattern extraction (PE) algorithm from SFS. After that, evaluating indicators inner-importance and inter-importance were designed to measure the noteworthiness of functions in DNFM algorithm. Finally, these functions were sorted by their noteworthiness. Comparison and contrast were conducted on the experiment results from two traditional complex network-based node mining methods, namely PageRank and DegreeRank. The results show that the DNFM method can mine noteworthy functions in software effectively and precisely. PMID:28278276

Dynamic fluctuation of proteins watched in real time

PubMed Central

Ormos, Pál

2008-01-01

The dynamic nature of protein function is a fundamental concept in the physics of proteins. Although the basic general ideas are well accepted most experimental evidence has an indirect nature. The detailed characterization of the dynamics is necessary for the understanding in detail. The dynamic fluctuations thought crucial for the function span an extremely broad time, starting from the picosecond regime. Recently, a few new experimental techniques emerged that permit the observation of dynamical phenomena directly. Notably, pulsed infrared (IR) spectroscopy has been applied with great success to observe structural changes with picosecond time resolution. Using two-dimensional-IR vibrational echo chemical exchange spectroscopy Ishikawa and co-workers [Ishikawa et al. (2008), Proc. Natl. Acad. Sci. U.S.A. 101, 14402–14407] managed to observe the transition between well defined conformational substrates of carbonmonoxy myoglobin directly. This is an important step in improving our insight into the details of protein function. PMID:19436491

The importance of hippocampal dynamic connectivity in explaining memory function in multiple sclerosis.

PubMed

van Geest, Quinten; Hulst, Hanneke E; Meijer, Kim A; Hoyng, Lieke; Geurts, Jeroen J G; Douw, Linda

2018-05-01

Brain dynamics (i.e., variable strength of communication between areas), even at the scale of seconds, are thought to underlie complex human behavior, such as learning and memory. In multiple sclerosis (MS), memory problems occur often and have so far only been related to "stationary" brain measures (e.g., atrophy, lesions, activation and stationary (s) functional connectivity (FC) over an entire functional scanning session). However, dynamics in FC (dFC) between the hippocampus and the (neo)cortex may be another important neurobiological substrate of memory impairment in MS that has not yet been explored. Therefore, we investigated hippocampal dFC during a functional (f) magnetic resonance imaging (MRI) episodic memory task and its relationship with verbal and visuospatial memory performance outside the MR scanner. Thirty-eight MS patients and 29 healthy controls underwent neuropsychological tests to assess memory function. Imaging (1.5T) was obtained during performance of a memory task. We assessed hippocampal volume, functional activation, and sFC (i.e., FC of the hippocampus with the rest of the brain averaged over the entire scan, using an atlas-based approach). Dynamic FC of the hippocampus was calculated using a sliding window approach. No group differences were found in hippocampal activation, sFC, and dFC. However, stepwise forward regression analyses in patients revealed that lower dFC of the left hippocampus (standardized β = -0.30; p  =   .021) could explain an additional 7% of variance (53% in total) in verbal memory, in addition to female sex and larger left hippocampal volume. For visuospatial memory, lower dFC of the right hippocampus (standardized β = -0.38; p  =   .013) could explain an additional 13% of variance (24% in total) in addition to higher sFC of the right hippocampus. Low hippocampal dFC is an important indicator for maintained memory performance in MS, in addition to other hippocampal imaging measures. Hence, brain dynamics may offer new insights into the neurobiological mechanisms underlying memory (dys)function.

Dynamic chest radiography: flat-panel detector (FPD) based functional X-ray imaging.

PubMed

Tanaka, Rie

2016-07-01

Dynamic chest radiography is a flat-panel detector (FPD)-based functional X-ray imaging, which is performed as an additional examination in chest radiography. The large field of view (FOV) of FPDs permits real-time observation of the entire lungs and simultaneous right-and-left evaluation of diaphragm kinetics. Most importantly, dynamic chest radiography provides pulmonary ventilation and circulation findings as slight changes in pixel value even without the use of contrast media; the interpretation is challenging and crucial for a better understanding of pulmonary function. The basic concept was proposed in the 1980s; however, it was not realized until the 2010s because of technical limitations. Dynamic FPDs and advanced digital image processing played a key role for clinical application of dynamic chest radiography. Pulmonary ventilation and circulation can be quantified and visualized for the diagnosis of pulmonary diseases. Dynamic chest radiography can be deployed as a simple and rapid means of functional imaging in both routine and emergency medicine. Here, we focus on the evaluation of pulmonary ventilation and circulation. This review article describes the basic mechanism of imaging findings according to pulmonary/circulation physiology, followed by imaging procedures, analysis method, and diagnostic performance of dynamic chest radiography.

BELOWGROUND NITROGEN UPTAKE AND ALLOCATION BY SPARTINA ALTERNIFLORA AND DISTICHLIS SPICATA

EPA Science Inventory

Anthropogenic nitrogen inputs coupled with rising sea level complicate predictions of marsh stability. As marsh stability is a function of its vegetation, it is important to understand the mechanisms that drive community dynamics. Many studies have examined aboveground dynamics a...

Theory of the dynamical thermal conductivity of metals

NASA Astrophysics Data System (ADS)

Bhalla, Pankaj; Kumar, Pradeep; Das, Nabyendu; Singh, Navinder

2016-09-01

The Mori's projection method, known as the memory function method, is an important theoretical formalism to study various transport coefficients. In the present work, we calculate the dynamical thermal conductivity in the case of metals using the memory function formalism. We introduce thermal memory functions for the first time and discuss the behavior of thermal conductivity in both the zero frequency limit and in the case of nonzero frequencies. We compare our results for the zero frequency case with the results obtained by the Bloch-Boltzmann kinetic approach and find that both approaches agree with each other. Motivated by some recent experimental advancements, we obtain several new results for the ac or the dynamical thermal conductivity.

Dynamic Reconstruction Algorithm of Three-Dimensional Temperature Field Measurement by Acoustic Tomography

PubMed Central

Li, Yanqiu; Liu, Shi; Inaki, Schlaberg H.

2017-01-01

Accuracy and speed of algorithms play an important role in the reconstruction of temperature field measurements by acoustic tomography. Existing algorithms are based on static models which only consider the measurement information. A dynamic model of three-dimensional temperature reconstruction by acoustic tomography is established in this paper. A dynamic algorithm is proposed considering both acoustic measurement information and the dynamic evolution information of the temperature field. An objective function is built which fuses measurement information and the space constraint of the temperature field with its dynamic evolution information. Robust estimation is used to extend the objective function. The method combines a tunneling algorithm and a local minimization technique to solve the objective function. Numerical simulations show that the image quality and noise immunity of the dynamic reconstruction algorithm are better when compared with static algorithms such as least square method, algebraic reconstruction technique and standard Tikhonov regularization algorithms. An effective method is provided for temperature field reconstruction by acoustic tomography. PMID:28895930

Animal pee in the sea: consumer-mediated nutrient dynamics in the world's changing oceans.

PubMed

Allgeier, Jacob E; Burkepile, Deron E; Layman, Craig A

2017-06-01

Humans have drastically altered the abundance of animals in marine ecosystems via exploitation. Reduced abundance can destabilize food webs, leading to cascading indirect effects that dramatically reorganize community structure and shift ecosystem function. However, the additional implications of these top-down changes for biogeochemical cycles via consumer-mediated nutrient dynamics (CND) are often overlooked in marine systems, particularly in coastal areas. Here, we review research that underscores the importance of this bottom-up control at local, regional, and global scales in coastal marine ecosystems, and the potential implications of anthropogenic change to fundamentally alter these processes. We focus attention on the two primary ways consumers affect nutrient dynamics, with emphasis on implications for the nutrient capacity of ecosystems: (1) the storage and retention of nutrients in biomass, and (2) the supply of nutrients via excretion and egestion. Nutrient storage in consumer biomass may be especially important in many marine ecosystems because consumers, as opposed to producers, often dominate organismal biomass. As for nutrient supply, we emphasize how consumers enhance primary production through both press and pulse dynamics. Looking forward, we explore the importance of CDN for improving theory (e.g., ecological stoichiometry, metabolic theory, and biodiversity-ecosystem function relationships), all in the context of global environmental change. Increasing research focus on CND will likely transform our perspectives on how consumers affect the functioning of marine ecosystems. © 2017 John Wiley & Sons Ltd.

The yeast actin cytoskeleton.

PubMed

Mishra, Mithilesh; Huang, Junqi; Balasubramanian, Mohan K

2014-03-01

The actin cytoskeleton is a complex network of dynamic polymers, which plays an important role in various fundamental cellular processes, including maintenance of cell shape, polarity, cell division, cell migration, endocytosis, vesicular trafficking, and mechanosensation. Precise spatiotemporal assembly and disassembly of actin structures is regulated by the coordinated activity of about 100 highly conserved accessory proteins, which nucleate, elongate, cross-link, and sever actin filaments. Both in vivo studies in a wide range of organisms from yeast to metazoans and in vitro studies of purified proteins have helped shape the current understanding of actin dynamics and function. Molecular genetics, genome-wide functional analysis, sophisticated real-time imaging, and ultrastructural studies in concert with biochemical analysis have made yeast an attractive model to understand the actin cytoskeleton, its molecular dynamics, and physiological function. Studies of the yeast actin cytoskeleton have contributed substantially in defining the universal mechanism regulating actin assembly and disassembly in eukaryotes. Here, we review some of the important insights generated by the study of actin cytoskeleton in two important yeast models the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Generalizing the extensibility of a dynamic geometry software

NASA Astrophysics Data System (ADS)

Herceg, Đorđe; Radaković, Davorka; Herceg, Dejana

2012-09-01

Plug-and-play visual components in a Dynamic Geometry Software (DGS) enable development of visually attractive, rich and highly interactive dynamic drawings. We are developing SLGeometry, a DGS that contains a custom programming language, a computer algebra system (CAS engine) and a graphics subsystem. The basic extensibility framework on SLGeometry supports dynamic addition of new functions from attribute annotated classes that implement runtime metadata registration in code. We present a general plug-in framework for dynamic importing of arbitrary Silverlight user interface (UI) controls into SLGeometry at runtime. The CAS engine maintains a metadata storage that describes each imported visual component and enables two-way communication between the expressions stored in the engine and the UI controls on the screen.

Binding Site Configurations Probe the Structure and Dynamics of the Zinc Finger of NEMO (NF-κB Essential Modulator).

PubMed

Godwin, Ryan C; Melvin, Ryan L; Gmeiner, William H; Salsbury, Freddie R

2017-01-31

Zinc-finger proteins are regulators of critical signaling pathways for various cellular functions, including apoptosis and oncogenesis. Here, we investigate how binding site protonation states and zinc coordination influence protein structure, dynamics, and ultimately function, as these pivotal regulatory proteins are increasingly important for protein engineering and therapeutic discovery. To better understand the thermodynamics and dynamics of the zinc finger of NEMO (NF-κB essential modulator), as well as the role of zinc, we present results of 20 μs molecular dynamics trajectories, 5 μs for each of four active site configurations. Consistent with experimental evidence, the zinc ion is essential for mechanical stabilization of the functional, folded conformation. Hydrogen bond motifs are unique for deprotonated configurations yet overlap in protonated cases. Correlated motions and principal component analysis corroborate the similarity of the protonated configurations and highlight unique relationships of the zinc-bound configuration. We hypothesize a potential mechanism for zinc binding from results of the thiol configurations. The deprotonated, zinc-bound configuration alone predominantly maintains its tertiary structure throughout all 5 μs and alludes rare conformations potentially important for (im)proper zinc-finger-related protein-protein or protein-DNA interactions.

Physiologic noise regression, motion regression, and TOAST dynamic field correction in complex-valued fMRI time series.

PubMed

Hahn, Andrew D; Rowe, Daniel B

2012-02-01

As more evidence is presented suggesting that the phase, as well as the magnitude, of functional MRI (fMRI) time series may contain important information and that there are theoretical drawbacks to modeling functional response in the magnitude alone, removing noise in the phase is becoming more important. Previous studies have shown that retrospective correction of noise from physiologic sources can remove significant phase variance and that dynamic main magnetic field correction and regression of estimated motion parameters also remove significant phase fluctuations. In this work, we investigate the performance of physiologic noise regression in a framework along with correction for dynamic main field fluctuations and motion regression. Our findings suggest that including physiologic regressors provides some benefit in terms of reduction in phase noise power, but it is small compared to the benefit of dynamic field corrections and use of estimated motion parameters as nuisance regressors. Additionally, we show that the use of all three techniques reduces phase variance substantially, removes undesirable spatial phase correlations and improves detection of the functional response in magnitude and phase. Copyright © 2011 Elsevier Inc. All rights reserved.

Dynamics and Context-Dependent Roles of DNA Methylation.

PubMed

Ambrosi, Christina; Manzo, Massimiliano; Baubec, Tuncay

2017-05-19

DNA methylation is one of the most extensively studied epigenetic marks. It is involved in transcriptional gene silencing and plays important roles during mammalian development. Its perturbation is often associated with human diseases. In mammalian genomes, DNA methylation is a prevalent modification that decorates the majority of cytosines. It is found at the promoters and enhancers of inactive genes, at repetitive elements, and within transcribed gene bodies. Its presence at promoters is dynamically linked to gene activity, suggesting that it could directly influence gene expression patterns and cellular identity. The genome-wide distribution and dynamic behaviour of this mark have been studied in great detail in a variety of tissues and cell lines, including early embryonic development and in embryonic stem cells. In combination with functional studies, these genome-wide maps of DNA methylation revealed interesting features of this mark and provided important insights into its dynamic nature and potential functional role in genome regulation. In this review, we discuss how these recent observations, in combination with insights obtained from biochemical and functional genetics studies, have expanded our current knowledge about the regulation and context-dependent roles of DNA methylation in mammalian genomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

High dynamic range image acquisition based on multiplex cameras

NASA Astrophysics Data System (ADS)

Zeng, Hairui; Sun, Huayan; Zhang, Tinghua

2018-03-01

High dynamic image is an important technology of photoelectric information acquisition, providing higher dynamic range and more image details, and it can better reflect the real environment, light and color information. Currently, the method of high dynamic range image synthesis based on different exposure image sequences cannot adapt to the dynamic scene. It fails to overcome the effects of moving targets, resulting in the phenomenon of ghost. Therefore, a new high dynamic range image acquisition method based on multiplex cameras system was proposed. Firstly, different exposure images sequences were captured with the camera array, using the method of derivative optical flow based on color gradient to get the deviation between images, and aligned the images. Then, the high dynamic range image fusion weighting function was established by combination of inverse camera response function and deviation between images, and was applied to generated a high dynamic range image. The experiments show that the proposed method can effectively obtain high dynamic images in dynamic scene, and achieves good results.

The Contribution of Mathematical Modeling to Understanding Dynamic Aspects of Rumen Metabolism

PubMed Central

Bannink, André; van Lingen, Henk J.; Ellis, Jennifer L.; France, James; Dijkstra, Jan

2016-01-01

All mechanistic rumen models cover the main drivers of variation in rumen function, which are feed intake, the differences between feedstuffs and feeds in their intrinsic rumen degradation characteristics, and fractional outflow rate of fluid and particulate matter. Dynamic modeling approaches are best suited to the prediction of more nuanced responses in rumen metabolism, and represent the dynamics of the interactions between substrates and micro-organisms and inter-microbial interactions. The concepts of dynamics are discussed for the case of rumen starch digestion as influenced by starch intake rate and frequency of feed intake, and for the case of fermentation of fiber in the large intestine. Adding representations of new functional classes of micro-organisms (i.e., with new characteristics from the perspective of whole rumen function) in rumen models only delivers new insights if complemented by the dynamics of their interactions with other functional classes. Rumen fermentation conditions have to be represented due to their profound impact on the dynamics of substrate degradation and microbial metabolism. Although the importance of rumen pH is generally acknowledged, more emphasis is needed on predicting its variation as well as variation in the processes that underlie rumen fluid dynamics. The rumen wall has an important role in adapting to rapid changes in the rumen environment, clearing of volatile fatty acids (VFA), and maintaining rumen pH within limits. Dynamics of rumen wall epithelia and their role in VFA absorption needs to be better represented in models that aim to predict rumen responses across nutritional or physiological states. For a detailed prediction of rumen N balance there is merit in a dynamic modeling approach compared to the static approaches adopted in current protein evaluation systems. Improvement is needed on previous attempts to predict rumen VFA profiles, and this should be pursued by introducing factors that relate more to microbial metabolism. For rumen model construction, data on rumen microbiomes are preferably coupled with knowledge consolidated in rumen models instead of relying on correlations with rather general aspects of treatment or animal. This helps to prevent the disregard of basic principles and underlying mechanisms of whole rumen function. PMID:27933039

Form follows function: the importance of endoplasmic reticulum shape.

PubMed

Westrate, L M; Lee, J E; Prinz, W A; Voeltz, G K

2015-01-01

The endoplasmic reticulum (ER) has a remarkably complex structure, composed of a single bilayer that forms the nuclear envelope, along with a network of sheets and dynamic tubules. Our understanding of the biological significance of the complex architecture of the ER has improved dramatically in the last few years. The identification of proteins and forces required for maintaining ER shape, as well as more advanced imaging techniques, has allowed the relationship between ER shape and function to come into focus. These studies have also revealed unexpected new functions of the ER and novel ER domains regulating alterations in ER dynamics. The importance of ER structure has become evident as recent research has identified diseases linked to mutations in ER-shaping proteins. In this review, we discuss what is known about the maintenance of ER architecture, the relationship between ER structure and function, and diseases associated with defects in ER structure.

Thermal quantum time-correlation functions from classical-like dynamics

NASA Astrophysics Data System (ADS)

Hele, Timothy J. H.

2017-07-01

Thermal quantum time-correlation functions are of fundamental importance in quantum dynamics, allowing experimentally measurable properties such as reaction rates, diffusion constants and vibrational spectra to be computed from first principles. Since the exact quantum solution scales exponentially with system size, there has been considerable effort in formulating reliable linear-scaling methods involving exact quantum statistics and approximate quantum dynamics modelled with classical-like trajectories. Here, we review recent progress in the field with the development of methods including centroid molecular dynamics , ring polymer molecular dynamics (RPMD) and thermostatted RPMD (TRPMD). We show how these methods have recently been obtained from 'Matsubara dynamics', a form of semiclassical dynamics which conserves the quantum Boltzmann distribution. We also apply the Matsubara formalism to reaction rate theory, rederiving t → 0+ quantum transition-state theory (QTST) and showing that Matsubara-TST, like RPMD-TST, is equivalent to QTST. We end by surveying areas for future progress.

Executive Functions and Prefrontal Cortex: A Matter of Persistence?

PubMed Central

Ball, Gareth; Stokes, Paul R.; Rhodes, Rebecca A.; Bose, Subrata K.; Rezek, Iead; Wink, Alle-Meije; Lord, Louis-David; Mehta, Mitul A.; Grasby, Paul M.; Turkheimer, Federico E.

2011-01-01

Executive function is thought to originates from the dynamics of frontal cortical networks. We examined the dynamic properties of the blood oxygen level dependent time-series measured with functional MRI (fMRI) within the prefrontal cortex (PFC) to test the hypothesis that temporally persistent neural activity underlies performance in three tasks of executive function. A numerical estimate of signal persistence, the Hurst exponent, postulated to represent the coherent firing of cortical networks, was determined and correlated with task performance. Increasing persistence in the lateral PFC was shown to correlate with improved performance during an n-back task. Conversely, we observed a correlation between persistence and increasing commission error – indicating a failure to inhibit a prepotent response – during a Go/No-Go task. We propose that persistence within the PFC reflects dynamic network formation and these findings underline the importance of frequency analysis of fMRI time-series in the study of executive functions. PMID:21286223

The importance of phrenic nerve preservation and its effect on long-term postoperative lung function after pneumonectomy.

PubMed

Kocher, Gregor J; Poulson, Jannie Lysgaard; Blichfeldt-Eckhardt, Morten Rune; Elle, Bo; Schmid, Ralph A; Licht, Peter B

2016-04-01

The importance of phrenic nerve preservation during pneumonectomy remains controversial. We previously demonstrated that preservation of the phrenic nerve in the immediate postoperative period preserved lung function by 3-5% but little is known about its long-term effects. We, therefore, decided to investigate the effect of temporary ipsilateral cervical phrenic nerve block on dynamic lung volumes in mid- to long-term pneumonectomy patients. We investigated 14 patients after a median of 9 years post pneumonectomy (range: 1-15 years). Lung function testing (spirometry) and fluoroscopic and/or sonographic assessment of diaphragmatic motion on the pneumonectomy side were performed before and after ultrasonographic-guided ipsilateral cervical phrenic nerve block by infiltration with lidocaine. Ipsilateral phrenic nerve block was successfully achieved in 12 patients (86%). In the remaining 2 patients, diaphragmatic motion was already paradoxical before the nerve block. We found no significant difference on dynamic lung function values (FEV1 'before' 1.39 ± 0.44 vs FEV1 'after' 1.38 ± 0.40; P = 0.81). Induction of a temporary diaphragmatic palsy did not significantly influence dynamic lung volumes in mid- to long-term pneumonectomy patients, suggesting that preservation of the phrenic nerve is of greater importance in the immediate postoperative period after pneumonectomy. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Microsecond protein dynamics observed at the single-molecule level

NASA Astrophysics Data System (ADS)

Otosu, Takuhiro; Ishii, Kunihiko; Tahara, Tahei

2015-07-01

How polypeptide chains acquire specific conformations to realize unique biological functions is a central problem of protein science. Single-molecule spectroscopy, combined with fluorescence resonance energy transfer, is utilized to study the conformational heterogeneity and the state-to-state transition dynamics of proteins on the submillisecond to second timescales. However, observation of the dynamics on the microsecond timescale is still very challenging. This timescale is important because the elementary processes of protein dynamics take place and direct comparison between experiment and simulation is possible. Here we report a new single-molecule technique to reveal the microsecond structural dynamics of proteins through correlation of the fluorescence lifetime. This method, two-dimensional fluorescence lifetime correlation spectroscopy, is applied to clarify the conformational dynamics of cytochrome c. Three conformational ensembles and the microsecond transitions in each ensemble are indicated from the correlation signal, demonstrating the importance of quantifying microsecond dynamics of proteins on the folding free energy landscape.

Microsecond protein dynamics observed at the single-molecule level

PubMed Central

Otosu, Takuhiro; Ishii, Kunihiko; Tahara, Tahei

2015-01-01

How polypeptide chains acquire specific conformations to realize unique biological functions is a central problem of protein science. Single-molecule spectroscopy, combined with fluorescence resonance energy transfer, is utilized to study the conformational heterogeneity and the state-to-state transition dynamics of proteins on the submillisecond to second timescales. However, observation of the dynamics on the microsecond timescale is still very challenging. This timescale is important because the elementary processes of protein dynamics take place and direct comparison between experiment and simulation is possible. Here we report a new single-molecule technique to reveal the microsecond structural dynamics of proteins through correlation of the fluorescence lifetime. This method, two-dimensional fluorescence lifetime correlation spectroscopy, is applied to clarify the conformational dynamics of cytochrome c. Three conformational ensembles and the microsecond transitions in each ensemble are indicated from the correlation signal, demonstrating the importance of quantifying microsecond dynamics of proteins on the folding free energy landscape. PMID:26151767

Dynamic Biological Functioning Important for Simulating and Stabilizing Ocean Biogeochemistry

NASA Astrophysics Data System (ADS)

Buchanan, P. J.; Matear, R. J.; Chase, Z.; Phipps, S. J.; Bindoff, N. L.

2018-04-01

The biogeochemistry of the ocean exerts a strong influence on the climate by modulating atmospheric greenhouse gases. In turn, ocean biogeochemistry depends on numerous physical and biological processes that change over space and time. Accurately simulating these processes is fundamental for accurately simulating the ocean's role within the climate. However, our simulation of these processes is often simplistic, despite a growing understanding of underlying biological dynamics. Here we explore how new parameterizations of biological processes affect simulated biogeochemical properties in a global ocean model. We combine 6 different physical realizations with 6 different biogeochemical parameterizations (36 unique ocean states). The biogeochemical parameterizations, all previously published, aim to more accurately represent the response of ocean biology to changing physical conditions. We make three major findings. First, oxygen, carbon, alkalinity, and phosphate fields are more sensitive to changes in the ocean's physical state. Only nitrate is more sensitive to changes in biological processes, and we suggest that assessment protocols for ocean biogeochemical models formally include the marine nitrogen cycle to assess their performance. Second, we show that dynamic variations in the production, remineralization, and stoichiometry of organic matter in response to changing environmental conditions benefit the simulation of ocean biogeochemistry. Third, dynamic biological functioning reduces the sensitivity of biogeochemical properties to physical change. Carbon and nitrogen inventories were 50% and 20% less sensitive to physical changes, respectively, in simulations that incorporated dynamic biological functioning. These results highlight the importance of a dynamic biology for ocean properties and climate.

Investigating the Temporal Patterns within and between Intrinsic Connectivity Networks under Eyes-Open and Eyes-Closed Resting States: A Dynamical Functional Connectivity Study Based on Phase Synchronization

PubMed Central

Wang, Xun-Heng; Li, Lihua; Xu, Tao; Ding, Zhongxiang

2015-01-01

The brain active patterns were organized differently under resting states of eyes open (EO) and eyes closed (EC). The altered voxel-wise and regional-wise resting state active patterns under EO/EC were found by static analysis. More importantly, dynamical spontaneous functional connectivity has been observed in the resting brain. To the best of our knowledge, the dynamical mechanisms of intrinsic connectivity networks (ICNs) under EO/EC remain largely unexplored. The goals of this paper were twofold: 1) investigating the dynamical intra-ICN and inter-ICN temporal patterns during resting state; 2) analyzing the altered dynamical temporal patterns of ICNs under EO/EC. To this end, a cohort of healthy subjects with scan conditions of EO/EC were recruited from 1000 Functional Connectomes Project. Through Hilbert transform, time-varying phase synchronization (PS) was applied to evaluate the inter-ICN synchrony. Meanwhile, time-varying amplitude was analyzed as dynamical intra-ICN temporal patterns. The results found six micro-states of inter-ICN synchrony. The medial visual network (MVN) showed decreased intra-ICN amplitude during EC relative to EO. The sensory-motor network (SMN) and auditory network (AN) exhibited enhanced intra-ICN amplitude during EC relative to EO. Altered inter-ICN PS was found between certain ICNs. Particularly, the SMN and AN exhibited enhanced PS to other ICNs during EC relative to EO. In addition, the intra-ICN amplitude might influence the inter-ICN synchrony. Moreover, default mode network (DMN) might play an important role in information processing during EO/EC. Together, the dynamical temporal patterns within and between ICNs were altered during different scan conditions of EO/EC. Overall, the dynamical intra-ICN and inter-ICN temporal patterns could benefit resting state fMRI-related research, and could be potential biomarkers for human functional connectome. PMID:26469182

Pipeline for inferring protein function from dynamics using coarse-grained molecular mechanics forcefield.

PubMed

Bhadra, Pratiti; Pal, Debnath

2017-04-01

Dynamics is integral to the function of proteins, yet the use of molecular dynamics (MD) simulation as a technique remains under-explored for molecular function inference. This is more important in the context of genomics projects where novel proteins are determined with limited evolutionary information. Recently we developed a method to match the query protein's flexible segments to infer function using a novel approach combining analysis of residue fluctuation-graphs and auto-correlation vectors derived from coarse-grained (CG) MD trajectory. The method was validated on a diverse dataset with sequence identity between proteins as low as 3%, with high function-recall rates. Here we share its implementation as a publicly accessible web service, named DynFunc (Dynamics Match for Function) to query protein function from ≥1 µs long CG dynamics trajectory information of protein subunits. Users are provided with the custom-developed coarse-grained molecular mechanics (CGMM) forcefield to generate the MD trajectories for their protein of interest. On upload of trajectory information, the DynFunc web server identifies specific flexible regions of the protein linked to putative molecular function. Our unique application does not use evolutionary information to infer molecular function from MD information and can, therefore, work for all proteins, including moonlighting and the novel ones, whenever structural information is available. Our pipeline is expected to be of utility to all structural biologists working with novel proteins and interested in moonlighting functions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Selection on Network Dynamics Drives Differential Rates of Protein Domain Evolution

PubMed Central

Mannakee, Brian K.; Gutenkunst, Ryan N.

2016-01-01

The long-held principle that functionally important proteins evolve slowly has recently been challenged by studies in mice and yeast showing that the severity of a protein knockout only weakly predicts that protein’s rate of evolution. However, the relevance of these studies to evolutionary changes within proteins is unknown, because amino acid substitutions, unlike knockouts, often only slightly perturb protein activity. To quantify the phenotypic effect of small biochemical perturbations, we developed an approach to use computational systems biology models to measure the influence of individual reaction rate constants on network dynamics. We show that this dynamical influence is predictive of protein domain evolutionary rate within networks in vertebrates and yeast, even after controlling for expression level and breadth, network topology, and knockout effect. Thus, our results not only demonstrate the importance of protein domain function in determining evolutionary rate, but also the power of systems biology modeling to uncover unanticipated evolutionary forces. PMID:27380265

Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function.

PubMed

Stockburger, Carola; Miano, Davide; Pallas, Thea; Friedland, Kristina; Müller, Walter E

2016-01-01

The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer's disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP) function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function.

Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function

PubMed Central

Stockburger, Carola; Miano, Davide; Pallas, Thea; Müller, Walter E.

2016-01-01

The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer's disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP) function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function. PMID:27747106

Dynamic gene expression analysis in a H1N1 influenza virus mouse pneumonia model.

PubMed

Bao, Yanyan; Gao, Yingjie; Shi, Yujing; Cui, Xiaolan

2017-06-01

H1N1, a major pathogenic subtype of influenza A virus, causes a respiratory infection in humans and livestock that can range from a mild infection to more severe pneumonia associated with acute respiratory distress syndrome. Understanding the dynamic changes in the genome and the related functional changes induced by H1N1 influenza virus infection is essential to elucidating the pathogenesis of this virus and thereby determining strategies to prevent future outbreaks. In this study, we filtered the significantly expressed genes in mouse pneumonia using mRNA microarray analysis. Using STC analysis, seven significant gene clusters were revealed, and using STC-GO analysis, we explored the significant functions of these seven gene clusters. The results revealed GOs related to H1N1 virus-induced inflammatory and immune functions, including innate immune response, inflammatory response, specific immune response, and cellular response to interferon-beta. Furthermore, the dynamic regulation relationships of the key genes in mouse pneumonia were revealed by dynamic gene network analysis, and the most important genes were filtered, including Dhx58, Cxcl10, Cxcl11, Zbp1, Ifit1, Ifih1, Trim25, Mx2, Oas2, Cd274, Irgm1, and Irf7. These results suggested that during mouse pneumonia, changes in the expression of gene clusters and the complex interactions among genes lead to significant changes in function. Dynamic gene expression analysis revealed key genes that performed important functions. These results are a prelude to advancements in mouse H1N1 influenza virus infection biology, as well as the use of mice as a model organism for human H1N1 influenza virus infection studies.

Multiscale regression modeling in mouse supraspinatus tendons reveals that dynamic processes act as mediators in structure-function relationships.

PubMed

Connizzo, Brianne K; Adams, Sheila M; Adams, Thomas H; Jawad, Abbas F; Birk, David E; Soslowsky, Louis J

2016-06-14

Recent advances in technology have allowed for the measurement of dynamic processes (re-alignment, crimp, deformation, sliding), but only a limited number of studies have investigated their relationship with mechanical properties. The overall objective of this study was to investigate the role of composition, structure, and the dynamic response to load in predicting tendon mechanical properties in a multi-level fashion mimicking native hierarchical collagen structure. Multiple linear regression models were investigated to determine the relationships between composition/structure, dynamic processes, and mechanical properties. Mediation was then used to determine if dynamic processes mediated structure-function relationships. Dynamic processes were strong predictors of mechanical properties. These predictions were location-dependent, with the insertion site utilizing all four dynamic responses and the midsubstance responding primarily with fibril deformation and sliding. In addition, dynamic processes were moderately predicted by composition and structure in a regionally-dependent manner. Finally, dynamic processes were partial mediators of the relationship between composition/structure and mechanical function, and results suggested that mediation is likely shared between multiple dynamic processes. In conclusion, the mechanical properties at the midsubstance of the tendon are controlled primarily by fibril structure and this region responds to load via fibril deformation and sliding. Conversely, the mechanical function at the insertion site is controlled by many other important parameters and the region responds to load via all four dynamic mechanisms. Overall, this study presents a strong foundation on which to design future experimental and modeling efforts in order to fully understand the complex structure-function relationships present in tendon. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sequence-specific backbone resonance assignments and microsecond timescale molecular dynamics simulation of human eosinophil-derived neurotoxin.

PubMed

Gagné, Donald; Narayanan, Chitra; Bafna, Khushboo; Charest, Laurie-Anne; Agarwal, Pratul K; Doucet, Nicolas

2017-10-01

Eight active canonical members of the pancreatic-like ribonuclease A (RNase A) superfamily have been identified in human. All structural homologs share similar RNA-degrading functions, while also cumulating other various biological activities in different tissues. The functional homologs eosinophil-derived neurotoxin (EDN, or RNase 2) and eosinophil cationic protein (ECP, or RNase 3) are known to be expressed and secreted by eosinophils in response to infection, and have thus been postulated to play an important role in host defense and inflammatory response. We recently initiated the biophysical and dynamical investigation of several vertebrate RNase homologs and observed that clustering residue dynamics appear to be linked with the phylogeny and biological specificity of several members. Here we report the 1 H, 13 C and 15 N backbone resonance assignments of human EDN (RNase 2) and its molecular dynamics simulation on the microsecond timescale, providing means to pursue this comparative atomic-scale functional and dynamical analysis by NMR and computation over multiple time frames.

Conformational Rigidity and Protein Dynamics at Distinct Timescales Regulate PTP1B Activity and Allostery.

PubMed

Choy, Meng S; Li, Yang; Machado, Luciana E S F; Kunze, Micha B A; Connors, Christopher R; Wei, Xingyu; Lindorff-Larsen, Kresten; Page, Rebecca; Peti, Wolfgang

2017-02-16

Protein function originates from a cooperation of structural rigidity, dynamics at different timescales, and allostery. However, how these three pillars of protein function are integrated is still only poorly understood. Here we show how these pillars are connected in Protein Tyrosine Phosphatase 1B (PTP1B), a drug target for diabetes and cancer that catalyzes the dephosphorylation of numerous substrates in essential signaling pathways. By combining new experimental and computational data on WT-PTP1B and ≥10 PTP1B variants in multiple states, we discovered a fundamental and evolutionarily conserved CH/π switch that is critical for positioning the catalytically important WPD loop. Furthermore, our data show that PTP1B uses conformational and dynamic allostery to regulate its activity. This shows that both conformational rigidity and dynamics are essential for controlling protein activity. This connection between rigidity and dynamics at different timescales is likely a hallmark of all enzyme function. Copyright © 2017 Elsevier Inc. All rights reserved.

Time-dependent density functional theory for open systems with a positivity-preserving decomposition scheme for environment spectral functions

NASA Astrophysics Data System (ADS)

Wang, RuLin; Zheng, Xiao; Kwok, YanHo; Xie, Hang; Chen, GuanHua; Yam, ChiYung

2015-04-01

Understanding electronic dynamics on material surfaces is fundamentally important for applications including nanoelectronics, inhomogeneous catalysis, and photovoltaics. Practical approaches based on time-dependent density functional theory for open systems have been developed to characterize the dissipative dynamics of electrons in bulk materials. The accuracy and reliability of such approaches depend critically on how the electronic structure and memory effects of surrounding material environment are accounted for. In this work, we develop a novel squared-Lorentzian decomposition scheme, which preserves the positive semi-definiteness of the environment spectral matrix. The resulting electronic dynamics is guaranteed to be both accurate and convergent even in the long-time limit. The long-time stability of electronic dynamics simulation is thus greatly improved within the current decomposition scheme. The validity and usefulness of our new approach are exemplified via two prototypical model systems: quasi-one-dimensional atomic chains and two-dimensional bilayer graphene.

Hydration status and diurnal trophic interactions shape microbial community function in desert biocrusts

NASA Astrophysics Data System (ADS)

Kim, Minsu; Or, Dani

2017-12-01

Biological soil crusts (biocrusts) are self-organised thin assemblies of microbes, lichens, and mosses that are ubiquitous in arid regions and serve as important ecological and biogeochemical hotspots. Biocrust ecological function is intricately shaped by strong gradients of water, light, oxygen, and dynamics in the abundance and spatial organisation of the microbial community within a few millimetres of the soil surface. We report a mechanistic model that links the biophysical and chemical processes that shape the functioning of biocrust representative microbial communities that interact trophically and respond dynamically to cycles of hydration, light, and temperature. The model captures key features of carbon and nitrogen cycling within biocrusts, such as microbial activity and distribution (during early stages of biocrust establishment) under diurnal cycles and the associated dynamics of biogeochemical fluxes at different hydration conditions. The study offers new insights into the highly dynamic and localised processes performed by microbial communities within thin desert biocrusts.

Functional connectivity dynamically evolves on multiple time-scales over a static structural connectome: Models and mechanisms.

PubMed

Cabral, Joana; Kringelbach, Morten L; Deco, Gustavo

2017-10-15

Over the last decade, we have observed a revolution in brain structural and functional Connectomics. On one hand, we have an ever-more detailed characterization of the brain's white matter structural connectome. On the other, we have a repertoire of consistent functional networks that form and dissipate over time during rest. Despite the evident spatial similarities between structural and functional connectivity, understanding how different time-evolving functional networks spontaneously emerge from a single structural network requires analyzing the problem from the perspective of complex network dynamics and dynamical system's theory. In that direction, bottom-up computational models are useful tools to test theoretical scenarios and depict the mechanisms at the genesis of resting-state activity. Here, we provide an overview of the different mechanistic scenarios proposed over the last decade via computational models. Importantly, we highlight the need of incorporating additional model constraints considering the properties observed at finer temporal scales with MEG and the dynamical properties of FC in order to refresh the list of candidate scenarios. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterizing and Differentiating Brain State Dynamics via Hidden Markov Models

PubMed Central

Ou, Jinli; Xie, Li; Jin, Changfeng; Li, Xiang; Zhu, Dajiang; Jiang, Rongxin; Chen, Yaowu

2014-01-01

Functional connectivity measured from resting state fMRI (R-fMRI) data has been widely used to examine the brain’s functional activities and has been recently used to characterize and differentiate brain conditions. However, the dynamical transition patterns of the brain’s functional states have been less explored. In this work, we propose a novel computational framework to quantitatively characterize the brain state dynamics via hidden Markov models (HMMs) learned from the observations of temporally dynamic functional connectomics, denoted as functional connectome states. The framework has been applied to the R-fMRI dataset including 44 post-traumatic stress disorder (PTSD) patients and 51 normal control (NC) subjects. Experimental results show that both PTSD and NC brains were undergoing remarkable changes in resting state and mainly transiting amongst a few brain states. Interestingly, further prediction with the best-matched HMM demonstrates that PTSD would enter into, but could not disengage from, a negative mood state. Importantly, 84 % of PTSD patients and 86 % of NC subjects are successfully classified via multiple HMMs using majority voting. PMID:25331991

Modelling oxygen transfer using dynamic alpha factors.

PubMed

Jiang, Lu-Man; Garrido-Baserba, Manel; Nolasco, Daniel; Al-Omari, Ahmed; DeClippeleir, Haydee; Murthy, Sudhir; Rosso, Diego

2017-11-01

Due to the importance of wastewater aeration in meeting treatment requirements and due to its elevated energy intensity, it is important to describe the real nature of an aeration system to improve design and specification, performance prediction, energy consumption, and process sustainability. Because organic loadings drive aeration efficiency to its lowest value when the oxygen demand (energy) is the highest, the implications of considering their dynamic nature on energy costs are of utmost importance. A dynamic model aimed at identifying conservation opportunities is presented. The model developed describes the correlation between the COD concentration and the α factor in activated sludge. Using the proposed model, the aeration efficiency is calculated as a function of the organic loading (i.e. COD). This results in predictions of oxygen transfer values that are more realistic than the traditional method of assuming constant α values. The model was applied to two water resource recovery facilities, and was calibrated and validated with time-sensitive databases. Our improved aeration model structure increases the quality of prediction of field data through the recognition of the dynamic nature of the alpha factor (α) as a function of the applied oxygen demand. For the cases presented herein, the model prediction of airflow improved by 20-35% when dynamic α is used. The proposed model offers a quantitative tool for the prediction of energy demand and for minimizing aeration design uncertainty. Copyright © 2017 Elsevier Ltd. All rights reserved.

DYNAMIC NEUROMUSCULAR STABILIZATION & SPORTS REHABILITATION

PubMed Central

Kobesova, Alena; Kolar, Pavel

2013-01-01

Dynamic neuromuscular (core) stability is necessary for optimal athletic performance and is not achieved purely by adequate strength of abdominals, spinal extensors, gluteals or any other musculature; rather, core stabilization is accomplished through precise coordination of these muscles and intra‐abdominal pressure regulation by the central nervous system. Understanding developmental kinesiology provides a framework to appreciate the regional interdependence and the inter‐linking of the skeleton, joints, musculature during movement and the importance of training both the dynamic and stabilizing function of muscles in the kinetic chain. The Dynamic Neuromuscular Stabilization (DNS) approach provides functional tools to assess and activate the intrinsic spinal stabilizers in order to optimize the movement system for both pre‐habilitation and rehabilitation of athletic injuries and performance. Level of Evidence: 5 PMID:23439921

Electron-Ion Dynamics with Time-Dependent Density Functional Theory: Towards Predictive Solar Cell Modeling: Final Technical Report

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

Maitra, Neepa

2016-07-14

This project investigates the accuracy of currently-used functionals in time-dependent density functional theory, which is today routinely used to predict and design materials and computationally model processes in solar energy conversion. The rigorously-based electron-ion dynamics method developed here sheds light on traditional methods and overcomes challenges those methods have. The fundamental research undertaken here is important for building reliable and practical methods for materials discovery. The ultimate goal is to use these tools for the computational design of new materials for solar cell devices of high efficiency.

Oscillations during observations: Dynamic oscillatory networks serving visuospatial attention.

PubMed

Wiesman, Alex I; Heinrichs-Graham, Elizabeth; Proskovec, Amy L; McDermott, Timothy J; Wilson, Tony W

2017-10-01

The dynamic allocation of neural resources to discrete features within a visual scene enables us to react quickly and accurately to salient environmental circumstances. A network of bilateral cortical regions is known to subserve such visuospatial attention functions; however the oscillatory and functional connectivity dynamics of information coding within this network are not fully understood. Particularly, the coding of information within prototypical attention-network hubs and the subsecond functional connections formed between these hubs have not been adequately characterized. Herein, we use the precise temporal resolution of magnetoencephalography (MEG) to define spectrally specific functional nodes and connections that underlie the deployment of attention in visual space. Twenty-three healthy young adults completed a visuospatial discrimination task designed to elicit multispectral activity in visual cortex during MEG, and the resulting data were preprocessed and reconstructed in the time-frequency domain. Oscillatory responses were projected to the cortical surface using a beamformer, and time series were extracted from peak voxels to examine their temporal evolution. Dynamic functional connectivity was then computed between nodes within each frequency band of interest. We find that visual attention network nodes are defined functionally by oscillatory frequency, that the allocation of attention to the visual space dynamically modulates functional connectivity between these regions on a millisecond timescale, and that these modulations significantly correlate with performance on a spatial discrimination task. We conclude that functional hubs underlying visuospatial attention are segregated not only anatomically but also by oscillatory frequency, and importantly that these oscillatory signatures promote dynamic communication between these hubs. Hum Brain Mapp 38:5128-5140, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Quantification of Interactions between Dynamic Cellular Network Functionalities by Cascaded Layering

PubMed Central

Prescott, Thomas P.; Lang, Moritz; Papachristodoulou, Antonis

2015-01-01

Large, naturally evolved biomolecular networks typically fulfil multiple functions. When modelling or redesigning such systems, functional subsystems are often analysed independently first, before subsequent integration into larger-scale computational models. In the design and analysis process, it is therefore important to quantitatively analyse and predict the dynamics of the interactions between integrated subsystems; in particular, how the incremental effect of integrating a subsystem into a network depends on the existing dynamics of that network. In this paper we present a framework for simulating the contribution of any given functional subsystem when integrated together with one or more other subsystems. This is achieved through a cascaded layering of a network into functional subsystems, where each layer is defined by an appropriate subset of the reactions. We exploit symmetries in our formulation to exhaustively quantify each subsystem’s incremental effects with minimal computational effort. When combining subsystems, their isolated behaviour may be amplified, attenuated, or be subject to more complicated effects. We propose the concept of mutual dynamics to quantify such nonlinear phenomena, thereby defining the incompatibility and cooperativity between all pairs of subsystems when integrated into any larger network. We exemplify our theoretical framework by analysing diverse behaviours in three dynamic models of signalling and metabolic pathways: the effect of crosstalk mechanisms on the dynamics of parallel signal transduction pathways; reciprocal side-effects between several integral feedback mechanisms and the subsystems they stabilise; and consequences of nonlinear interactions between elementary flux modes in glycolysis for metabolic engineering strategies. Our analysis shows that it is not sufficient to just specify subsystems and analyse their pairwise interactions; the environment in which the interaction takes place must also be explicitly defined. Our framework provides a natural representation of nonlinear interaction phenomena, and will therefore be an important tool for modelling large-scale evolved or synthetic biomolecular networks. PMID:25933116

Unraveling secrets of telomeres: one molecule at a time

PubMed Central

Lin, Jiangguo; Kaur, Parminder; Countryman, Preston; Opresko, Patricia L.; Wang, Hong

2016-01-01

Telomeres play important roles in maintaining the stability of linear chromosomes. Telomere maintenance involves dynamic actions of multiple proteins interacting with long repetitive sequences and complex dynamic DNA structures, such as G-quadruplexes, T-loops and t-circles. Given the heterogeneity and complexity of telomeres, single-molecule approaches are essential to fully understand the structure-function relationships that govern telomere maintenance. In this review, we present a brief overview of the principles of single-molecule imaging and manipulation techniques. We then highlight results obtained from applying these single-molecule techniques for studying structure, dynamics and functions of G-quadruplexes, telomerase, and shelterin proteins. PMID:24569170

Clean energy storage technology in the making: An innovation systems perspective on flywheel energy storage.

PubMed

Wicki, Samuel; Hansen, Erik G

2017-09-20

The emergence and diffusion of green and sustainable technologies is full of obstacles and has therefore become an important area of research. We are interested in further understanding the dynamics between entrepreneurial experimentation, market formation, and institutional contexts, together playing a decisive role for successful diffusion of such technologies. Accordingly, we study these processes by adopting a technological innovation system perspective focusing on actors, networks, and institutions as well as the functions provided by them. Using a qualitative case study research design, we focus on the high-speed flywheel energy storage technology. As flywheels are based on a rotating mass allowing short-term storage of energy in kinetic form, they represent an environmentally-friendly alternative to electrochemical batteries and therefore can play an important role in sustainable energy transitions. Our contribution is threefold: First , regarding the flywheel energy storage technology, our findings reveal two subsystems and related markets in which development took different courses. In the automotive sector, flywheels are developing well as a braking energy recovery technology under the influence of two motors of innovation. In the electricity sector, they are stagnating at the stage of demonstration projects because of two important system weaknesses that counteract demand for storage. Second , we contribute to the theory of technological innovation systems by better understanding the internal dynamics between different functions of an innovation system as well as between the innovation system and its (external) contextual structures. Our third contribution is methodological. According to our best knowledge, we are the first to use system dynamics to (qualitatively) analyze and visualize dynamics between the diverse functions of innovation systems with the aim of enabling a better understanding of complex and iterative system processes. The paper also derives important implications for energy scholars, flywheel practitioners, and policymakers.

Von Bertalanffy's dynamics under a polynomial correction: Allee effect and big bang bifurcation

NASA Astrophysics Data System (ADS)

Leonel Rocha, J.; Taha, A. K.; Fournier-Prunaret, D.

2016-02-01

In this work we consider new one-dimensional populational discrete dynamical systems in which the growth of the population is described by a family of von Bertalanffy's functions, as a dynamical approach to von Bertalanffy's growth equation. The purpose of introducing Allee effect in those models is satisfied under a correction factor of polynomial type. We study classes of von Bertalanffy's functions with different types of Allee effect: strong and weak Allee's functions. Dependent on the variation of four parameters, von Bertalanffy's functions also includes another class of important functions: functions with no Allee effect. The complex bifurcation structures of these von Bertalanffy's functions is investigated in detail. We verified that this family of functions has particular bifurcation structures: the big bang bifurcation of the so-called “box-within-a-box” type. The big bang bifurcation is associated to the asymptotic weight or carrying capacity. This work is a contribution to the study of the big bang bifurcation analysis for continuous maps and their relationship with explosion birth and extinction phenomena.

Molecular dynamics simulations of a K+ channel blocker: Tc1 toxin from Tityus cambridgei.

PubMed

Grottesi, Alessandro; Sansom, Mark S P

2003-01-30

Toxins that block voltage-gated potassium (Kv) channels provide a possible template for improved homology models of the Kv pore. In assessing the interactions of Kv channels and their toxins it is important to determine the dynamic flexibility of the toxins. Multiple 10 ns duration molecular dynamics simulations combined with essential dynamics analysis have been used to explore the flexibility of four different Kv channel-blocking toxins. Three toxins (Tc1, AgTx and ChTx) share a common fold. They also share a common pattern of conformational dynamics, as revealed by essential dynamics analysis of the simulation results. This suggests that some aspects of dynamic behaviour are conserved across a single protein fold class. In each of these three toxins, the residue exhibiting minimum flexibility corresponds to a conserved lysine residue that is suggested to interact with the filter domain of the channel. Thus, comparative simulations reveal functionally important conservation of molecular dynamics as well as protein fold across a family of related toxins.

Exercise Dynamics in Secondary Mitral Regurgitation: Pathophysiology and Therapeutic Implications

PubMed Central

Bertrand, Philippe B.; Schwammenthal, Ehud; Levine, Robert A.; Vandervoort, Pieter M.

2016-01-01

Secondary mitral valve regurgitation (MR) remains a challenging problem in the diagnostic work-up and treatment of heart failure patients. Although secondary MR is characteristically dynamic in nature and sensitive to changes in ventricular geometry and loading, current therapy is mainly focused on resting conditions. Exercise-induced increase in secondary MR, however, is associated with impaired exercise capacity and increased mortality. In an era where a multitude of percutaneous solutions are emerging for the treatment of HF patients it becomes important to address the dynamic component of secondary MR during exercise as well. A critical reappraisal of the underlying disease mechanisms, and in particular of the dynamic component during exercise is of timely importance. This review summarizes the pathophysiologic mechanisms involved in the dynamic deterioration of secondary MR during exercise, its functional and prognostic impact, and the way current treatment options affect the dynamic lesion and exercise hemodynamics in general. PMID:28093494

Chunking dynamics: heteroclinics in mind

PubMed Central

Rabinovich, Mikhail I.; Varona, Pablo; Tristan, Irma; Afraimovich, Valentin S.

2014-01-01

Recent results of imaging technologies and non-linear dynamics make possible to relate the structure and dynamics of functional brain networks to different mental tasks and to build theoretical models for the description and prediction of cognitive activity. Such models are non-linear dynamical descriptions of the interaction of the core components—brain modes—participating in a specific mental function. The dynamical images of different mental processes depend on their temporal features. The dynamics of many cognitive functions are transient. They are often observed as a chain of sequentially changing metastable states. A stable heteroclinic channel (SHC) consisting of a chain of saddles—metastable states—connected by unstable separatrices is a mathematical image for robust transients. In this paper we focus on hierarchical chunking dynamics that can represent several forms of transient cognitive activity. Chunking is a dynamical phenomenon that nature uses to perform information processing of long sequences by dividing them in shorter information items. Chunking, for example, makes more efficient the use of short-term memory by breaking up long strings of information (like in language where one can see the separation of a novel on chapters, paragraphs, sentences, and finally words). Chunking is important in many processes of perception, learning, and cognition in humans and animals. Based on anatomical information about the hierarchical organization of functional brain networks, we propose a cognitive network architecture that hierarchically chunks and super-chunks switching sequences of metastable states produced by winnerless competitive heteroclinic dynamics. PMID:24672469

Chunking dynamics: heteroclinics in mind.

PubMed

Rabinovich, Mikhail I; Varona, Pablo; Tristan, Irma; Afraimovich, Valentin S

2014-01-01

Recent results of imaging technologies and non-linear dynamics make possible to relate the structure and dynamics of functional brain networks to different mental tasks and to build theoretical models for the description and prediction of cognitive activity. Such models are non-linear dynamical descriptions of the interaction of the core components-brain modes-participating in a specific mental function. The dynamical images of different mental processes depend on their temporal features. The dynamics of many cognitive functions are transient. They are often observed as a chain of sequentially changing metastable states. A stable heteroclinic channel (SHC) consisting of a chain of saddles-metastable states-connected by unstable separatrices is a mathematical image for robust transients. In this paper we focus on hierarchical chunking dynamics that can represent several forms of transient cognitive activity. Chunking is a dynamical phenomenon that nature uses to perform information processing of long sequences by dividing them in shorter information items. Chunking, for example, makes more efficient the use of short-term memory by breaking up long strings of information (like in language where one can see the separation of a novel on chapters, paragraphs, sentences, and finally words). Chunking is important in many processes of perception, learning, and cognition in humans and animals. Based on anatomical information about the hierarchical organization of functional brain networks, we propose a cognitive network architecture that hierarchically chunks and super-chunks switching sequences of metastable states produced by winnerless competitive heteroclinic dynamics.

Engineered control of enzyme structural dynamics and function.

PubMed

Boehr, David D; D'Amico, Rebecca N; O'Rourke, Kathleen F

2018-04-01

Enzymes undergo a range of internal motions from local, active site fluctuations to large-scale, global conformational changes. These motions are often important for enzyme function, including in ligand binding and dissociation and even preparing the active site for chemical catalysis. Protein engineering efforts have been directed towards manipulating enzyme structural dynamics and conformational changes, including targeting specific amino acid interactions and creation of chimeric enzymes with new regulatory functions. Post-translational covalent modification can provide an additional level of enzyme control. These studies have not only provided insights into the functional role of protein motions, but they offer opportunities to create stimulus-responsive enzymes. These enzymes can be engineered to respond to a number of external stimuli, including light, pH, and the presence of novel allosteric modulators. Altogether, the ability to engineer and control enzyme structural dynamics can provide new tools for biotechnology and medicine. © 2018 The Protein Society.

Partial cooperative unfolding in proteins as observed by hydrogen exchange mass spectrometry

PubMed Central

Engen, John R.; Wales, Thomas E.; Chen, Shugui; Marzluff, Elaine M.; Hassell, Kerry M.; Weis, David D.; Smithgall, Thomas E.

2013-01-01

Many proteins do not exist in a single rigid conformation. Protein motions, or dynamics, exist and in many cases are important for protein function. The analysis of protein dynamics relies on biophysical techniques that can distinguish simultaneously existing populations of molecules and their rates of interconversion. Hydrogen exchange (HX) detected by mass spectrometry (MS) is contributing to our understanding of protein motions by revealing unfolding and dynamics on a wide timescale, ranging from seconds to hours to days. In this review we discuss HX MS-based analyses of protein dynamics, using our studies of multi-domain kinases as examples. Using HX MS, we have successfully probed protein dynamics and unfolding in the isolated SH3, SH2 and kinase domains of the c-Src and Abl kinase families, as well as the role of inter- and intra-molecular interactions in the global control of kinase function. Coupled with high-resolution structural information, HX MS has proved to be a powerful and versatile tool for the analysis of the conformational dynamics in these kinase systems, and has provided fresh insight regarding the regulatory control of these important signaling proteins. HX MS studies of dynamics are applicable not only to the proteins we illustrate here, but to a very wide range of proteins and protein systems, and should play a role in both classification of and greater understanding of the prevalence of protein motion. PMID:23682200

Accurately Characterizing the Importance of Wave-Particle Interactions in Radiation Belt Dynamics: The Pitfalls of Statistical Wave Representations

NASA Technical Reports Server (NTRS)

Murphy, Kyle R.; Mann, Ian R.; Rae, I. Jonathan; Sibeck, David G.; Watt, Clare E. J.

2016-01-01

Wave-particle interactions play a crucial role in energetic particle dynamics in the Earths radiation belts. However, the relative importance of different wave modes in these dynamics is poorly understood. Typically, this is assessed during geomagnetic storms using statistically averaged empirical wave models as a function of geomagnetic activity in advanced radiation belt simulations. However, statistical averages poorly characterize extreme events such as geomagnetic storms in that storm-time ultralow frequency wave power is typically larger than that derived over a solar cycle and Kp is a poor proxy for storm-time wave power.

SNAG AND LARGE WOODY DEBRIS DYNAMICS IN RIPARIAN FORESTS

EPA Science Inventory

Important components of riparian forests are snags and streamside large woody debris (LWD) because they are functional in maintaining water quality and providing habitat for numerous plants and animals. To effectively manage riparian forests, it is important to understand the dy...

Exploration of Multi-State Conformational Dynamics and Underlying Global Functional Landscape of Maltose Binding Protein

PubMed Central

Wang, Yong; Tang, Chun; Wang, Erkang; Wang, Jin

2012-01-01

An increasing number of biological machines have been revealed to have more than two macroscopic states. Quantifying the underlying multiple-basin functional landscape is essential for understanding their functions. However, the present models seem to be insufficient to describe such multiple-state systems. To meet this challenge, we have developed a coarse grained triple-basin structure-based model with implicit ligand. Based on our model, the constructed functional landscape is sufficiently sampled by the brute-force molecular dynamics simulation. We explored maltose-binding protein (MBP) which undergoes large-scale domain motion between open, apo-closed (partially closed) and holo-closed (fully closed) states responding to ligand binding. We revealed an underlying mechanism whereby major induced fit and minor population shift pathways co-exist by quantitative flux analysis. We found that the hinge regions play an important role in the functional dynamics as well as that increases in its flexibility promote population shifts. This finding provides a theoretical explanation of the mechanistic discrepancies in PBP protein family. We also found a functional “backtracking” behavior that favors conformational change. We further explored the underlying folding landscape in response to ligand binding. Consistent with earlier experimental findings, the presence of ligand increases the cooperativity and stability of MBP. This work provides the first study to explore the folding dynamics and functional dynamics under the same theoretical framework using our triple-basin functional model. PMID:22532792

The non-linear relationship between body size and function in parrotfishes

NASA Astrophysics Data System (ADS)

Lokrantz, J.; Nyström, M.; Thyresson, M.; Johansson, C.

2008-12-01

Parrotfishes are a group of herbivores that play an important functional role in structuring benthic communities on coral reefs. Increasingly, these fish are being targeted by fishermen, and resultant declines in biomass and abundance may have severe consequences for the dynamics and regeneration of coral reefs. However, the impact of overfishing extends beyond declining fish stocks. It can also lead to demographic changes within species populations where mean body size is reduced. The effect of reduced mean body size on population dynamics is well described in literature but virtually no information exists on how this may influence important ecological functions. The study investigated how one important function, scraping (i.e., the capacity to remove algae and open up bare substratum for coral larval settlement), by three common species of parrotfishes ( Scarus niger, Chlorurus sordidus, and Chlorurus strongylocephalus) on coral reefs at Zanzibar (Tanzania) was influenced by the size of individual fishes. There was a non-linear relationship between body size and scraping function for all species examined, and impact through scraping was also found to increase markedly when fish reached a size of 15 20 cm. Thus, coral reefs which have a high abundance and biomass of parrotfish may nonetheless be functionally impaired if dominated by small-sized individuals. Reductions in mean body size within parrotfish populations could, therefore, have functional impacts on coral reefs that previously have been overlooked.

Emergence of Rich-Club Topology and Coordinated Dynamics in Development of Hippocampal Functional Networks In Vitro

PubMed Central

Charlesworth, Paul; Kitzbichler, Manfred G.; Paulsen, Ole

2015-01-01

Recent studies demonstrated that the anatomical network of the human brain shows a “rich-club” organization. This complex topological feature implies that highly connected regions, hubs of the large-scale brain network, are more densely interconnected with each other than expected by chance. Rich-club nodes were traversed by a majority of short paths between peripheral regions, underlining their potential importance for efficient global exchange of information between functionally specialized areas of the brain. Network hubs have also been described at the microscale of brain connectivity (so-called “hub neurons”). Their role in shaping synchronous dynamics and forming microcircuit wiring during development, however, is not yet fully understood. The present study aimed to investigate the role of hubs during network development, using multi-electrode arrays and functional connectivity analysis during spontaneous multi-unit activity (MUA) of dissociated primary mouse hippocampal neurons. Over the first 4 weeks in vitro, functional connectivity significantly increased in strength, density, and size, with mature networks demonstrating a robust modular and small-world topology. As expected by a “rich-get-richer” growth rule of network evolution, MUA graphs were found to form rich-clubs at an early stage in development (14 DIV). Later on, rich-club nodes were a consistent topological feature of MUA graphs, demonstrating high nodal strength, efficiency, and centrality. Rich-club nodes were also found to be crucial for MUA dynamics. They often served as broker of spontaneous activity flow, confirming that hub nodes and rich-clubs may play an important role in coordinating functional dynamics at the microcircuit level. PMID:25855164

Extra permeability is required to model dynamic oxygen measurements: evidence for functional recruitment?

PubMed Central

Barrett, Matthew JP; Suresh, Vinod

2013-01-01

Neural activation triggers a rapid, focal increase in blood flow and thus oxygen delivery. Local oxygen consumption also increases, although not to the same extent as oxygen delivery. This ‘uncoupling' enables a number of widely-used functional neuroimaging techniques; however, the physiologic mechanisms that govern oxygen transport under these conditions remain unclear. Here, we explore this dynamic process using a new mathematical model. Motivated by experimental observations and previous modeling, we hypothesized that functional recruitment of capillaries has an important role during neural activation. Using conventional mechanisms alone, the model predictions were inconsistent with in vivo measurements of oxygen partial pressure. However, dynamically increasing net capillary permeability, a simple description of functional recruitment, led to predictions consistent with the data. Increasing permeability in all vessel types had the same effect, but two alternative mechanisms were unable to produce predictions consistent with the data. These results are further evidence that conventional models of oxygen transport are not sufficient to predict dynamic experimental data. The data and modeling suggest that it is necessary to include a mechanism that dynamically increases net vascular permeability. While the model cannot distinguish between the different possibilities, we speculate that functional recruitment could have this effect in vivo. PMID:23673433

Exploration of the Energy Landscape of Acetylcholinesterase by Molecular Dynamics Simulation.

NASA Astrophysics Data System (ADS)

McCammon, J. Andrew

2002-03-01

Proteins have rough energy landscapes. Often more states than just the ground state are occupied and have biological functions. It is essential to study these conformational substates and the dynamical transitions among them. Acetylcholinesterase (AChE) is an important enzyme that has biological functions including the termination of synaptic transmission signals. X-ray structures show that it has an active site that is accessible only via a long and narrow channel from its surface. Therefore the fact that acetylcholine and larger ligands can reach the active site is believed to reflect the protein's structural fluctuation. We carried out long molecular dynamics simulations to investigate the dynamics of AChE and its relation to biological function, and compared our results with experiments. The results reveal several "doors" that open intermittantly between the active site and the surface. Instead of having simple exponential decay correlation functions, the time series of these channels reveal complex, fractal gating between conformations. We also compared the AChE dynamics data with those from an AchE-fasciculin complex. (Fasciculin is a small protein that is a natural inhibitor of AChE.) The results show remarkable effects of the protein-protein interaction, including allosteric and dynamical inhibition by fasciculin besides direct steric blocking. More information and images can be found at http://mccammon.ucsd.edu

The Mathematics of Psychotherapy: A Nonlinear Model of Change Dynamics.

PubMed

Schiepek, Gunter; Aas, Benjamin; Viol, Kathrin

2016-07-01

Psychotherapy is a dynamic process produced by a complex system of interacting variables. Even though there are qualitative models of such systems the link between structure and function, between network and network dynamics is still missing. The aim of this study is to realize these links. The proposed model is composed of five state variables (P: problem severity, S: success and therapeutic progress, M: motivation to change, E: emotions, I: insight and new perspectives) interconnected by 16 functions. The shape of each function is modified by four parameters (a: capability to form a trustful working alliance, c: mentalization and emotion regulation, r: behavioral resources and skills, m: self-efficacy and reward expectation). Psychologically, the parameters play the role of competencies or traits, which translate into the concept of control parameters in synergetics. The qualitative model was transferred into five coupled, deterministic, nonlinear difference equations generating the dynamics of each variable as a function of other variables. The mathematical model is able to reproduce important features of psychotherapy processes. Examples of parameter-dependent bifurcation diagrams are given. Beyond the illustrated similarities between simulated and empirical dynamics, the model has to be further developed, systematically tested by simulated experiments, and compared to empirical data.

Molecular dynamics simulations of Hsp40 J-domain mutants identifies disruption of the critical HPD-motif as the key factor for impaired curing in vivo of the yeast prion [URE3].

PubMed

Xue, You-Lin; Wang, Hao; Riedy, Michael; Roberts, Brittany-Lee; Sun, Yuna; Song, Yong-Bo; Jones, Gary W; Masison, Daniel C; Song, Youtao

2018-05-01

Genetic screens using Saccharomyces cerevisiae have identified an array of Hsp40 (Ydj1p) J-domain mutants that are impaired in the ability to cure the yeast [URE3] prion through disrupting functional interactions with Hsp70. However, biochemical analysis of some of these Hsp40 J-domain mutants has so far failed to provide major insight into the specific functional changes in Hsp40-Hsp70 interactions. To explore the detailed structural and dynamic properties of the Hsp40 J-domain, 20 ns molecular dynamic simulations of 4 mutants (D9A, D36A, A30T, and F45S) and wild-type J-domain were performed, followed by Hsp70 docking simulations. Results demonstrated that although the Hsp70 interaction mechanism of the mutants may vary, the major structural change was targeted to the critical HPD motif of the J-domain. Our computational analysis fits well with previous yeast genetics studies regarding highlighting the importance of J-domain function in prion propagation. During the molecular dynamics simulations several important residues were identified and predicted to play an essential role in J-domain structure. Among these residues, Y26 and F45 were confirmed, using both in silico and in vivo methods, as being critical for Ydj1p function.

Probing the structural and dynamical properties of liquid water with models including non-local electron correlation

NASA Astrophysics Data System (ADS)

Del Ben, Mauro; Hutter, Jürg; VandeVondele, Joost

2015-08-01

Water is a ubiquitous liquid that displays a wide range of anomalous properties and has a delicate structure that challenges experiment and simulation alike. The various intermolecular interactions that play an important role, such as repulsion, polarization, hydrogen bonding, and van der Waals interactions, are often difficult to reproduce faithfully in atomistic models. Here, electronic structure theories including all these interactions at equal footing, which requires the inclusion of non-local electron correlation, are used to describe structure and dynamics of bulk liquid water. Isobaric-isothermal (NpT) ensemble simulations based on the Random Phase Approximation (RPA) yield excellent density (0.994 g/ml) and fair radial distribution functions, while various other density functional approximations produce scattered results (0.8-1.2 g/ml). Molecular dynamics simulation in the microcanonical (NVE) ensemble based on Møller-Plesset perturbation theory (MP2) yields dynamical properties in the condensed phase, namely, the infrared spectrum and diffusion constant. At the MP2 and RPA levels of theory, ice is correctly predicted to float on water, resolving one of the anomalies as resulting from a delicate balance between van der Waals and hydrogen bonding interactions. For several properties, obtaining quantitative agreement with experiment requires correction for nuclear quantum effects (NQEs), highlighting their importance, for structure, dynamics, and electronic properties. A computed NQE shift of 0.6 eV for the band gap and absorption spectrum illustrates the latter. Giving access to both structure and dynamics of condensed phase systems, non-local electron correlation will increasingly be used to study systems where weak interactions are of paramount importance.

Coupled binding-bending-folding: The complex conformational dynamics of protein-DNA binding studied by atomistic molecular dynamics simulations.

PubMed

van der Vaart, Arjan

2015-05-01

Protein-DNA binding often involves dramatic conformational changes such as protein folding and DNA bending. While thermodynamic aspects of this behavior are understood, and its biological function is often known, the mechanism by which the conformational changes occur is generally unclear. By providing detailed structural and energetic data, molecular dynamics simulations have been helpful in elucidating and rationalizing protein-DNA binding. This review will summarize recent atomistic molecular dynamics simulations of the conformational dynamics of DNA and protein-DNA binding. A brief overview of recent developments in DNA force fields is given as well. Simulations have been crucial in rationalizing the intrinsic flexibility of DNA, and have been instrumental in identifying the sequence of binding events, the triggers for the conformational motion, and the mechanism of binding for a number of important DNA-binding proteins. Molecular dynamics simulations are an important tool for understanding the complex binding behavior of DNA-binding proteins. With recent advances in force fields and rapid increases in simulation time scales, simulations will become even more important for future studies. This article is part of a Special Issue entitled Recent developments of molecular dynamics. Copyright © 2014. Published by Elsevier B.V.

Single-Molecule FRET Spectroscopy and the Polymer Physics of Unfolded and Intrinsically Disordered Proteins.

PubMed

Schuler, Benjamin; Soranno, Andrea; Hofmann, Hagen; Nettels, Daniel

2016-07-05

The properties of unfolded proteins have long been of interest because of their importance to the protein folding process. Recently, the surprising prevalence of unstructured regions or entirely disordered proteins under physiological conditions has led to the realization that such intrinsically disordered proteins can be functional even in the absence of a folded structure. However, owing to their broad conformational distributions, many of the properties of unstructured proteins are difficult to describe with the established concepts of structural biology. We have thus seen a reemergence of polymer physics as a versatile framework for understanding their structure and dynamics. An important driving force for these developments has been single-molecule spectroscopy, as it allows structural heterogeneity, intramolecular distance distributions, and dynamics to be quantified over a wide range of timescales and solution conditions. Polymer concepts provide an important basis for relating the physical properties of unstructured proteins to folding and function.

Modifications in small nuclear RNAs and their roles in spliceosome assembly and function.

PubMed

Bohnsack, Markus T; Sloan, Katherine E

2018-06-01

Modifications in cellular RNAs have emerged as key regulators of all aspects of gene expression, including pre-mRNA splicing. During spliceosome assembly and function, the small nuclear RNAs (snRNAs) form numerous dynamic RNA-RNA and RNA-protein interactions, which are required for spliceosome assembly, correct positioning of the spliceosome on substrate pre-mRNAs and catalysis. The human snRNAs contain several base methylations as well as a myriad of pseudouridines and 2'-O-methylated nucleotides, which are largely introduced by small Cajal body-specific-RNPs. Modified nucleotides typically cluster in functionally important regions of the snRNAs, suggesting that their presence could optimise the interactions of snRNAs with each other or with pre-mRNAs, or may affect the binding of spliceosomal proteins. snRNA modifications appear to play important roles in snRNP biogenesis and spliceosome assembly, and have also been proposed to influence the efficiency and fidelity of pre-mRNAs splicing. Interestingly, alterations in the modification status of snRNAs have recently been observed in different cellular conditions, implying that some snRNA modifications are dynamic and raising the possibility that these modifications may fine-tune the spliceosome for particular functions. Here, we review the current knowledge on the snRNA modification machinery and discuss the timing, functions and dynamics of modifications in snRNAs.

Time-Ordered Networks Reveal Limitations to Information Flow in Ant Colonies

PubMed Central

Blonder, Benjamin; Dornhaus, Anna

2011-01-01

Background An important function of many complex networks is to inhibit or promote the transmission of disease, resources, or information between individuals. However, little is known about how the temporal dynamics of individual-level interactions affect these networks and constrain their function. Ant colonies are a model comparative system for understanding general principles linking individual-level interactions to network-level functions because interactions among individuals enable integration of multiple sources of information to collectively make decisions, and allocate tasks and resources. Methodology/Findings Here we show how the temporal and spatial dynamics of such individual interactions provide upper bounds to rates of colony-level information flow in the ant Temnothorax rugatulus. We develop a general framework for analyzing dynamic networks and a mathematical model that predicts how information flow scales with individual mobility and group size. Conclusions/Significance Using thousands of time-stamped interactions between uniquely marked ants in four colonies of a range of sizes, we demonstrate that observed maximum rates of information flow are always slower than predicted, and are constrained by regulation of individual mobility and contact rate. By accounting for the ordering and timing of interactions, we can resolve important difficulties with network sampling frequency and duration, enabling a broader understanding of interaction network functioning across systems and scales. PMID:21625450

Thumb-loops up for catalysis: a structure/function investigation of a functional loop movement in a GH11 xylanase

PubMed Central

Paës, Gabriel; Cortés, Juan; Siméon, Thierry; O'Donohue, Michael J.; Tran, Vinh

2012-01-01

Dynamics is a key feature of enzyme catalysis. Unfortunately, current experimental and computational techniques do not yet provide a comprehensive understanding and description of functional macromolecular motions. In this work, we have extended a novel computational technique, which combines molecular modeling methods and robotics algorithms, to investigate functional motions of protein loops. This new approach has been applied to study the functional importance of the so-called thumb-loop in the glycoside hydrolase family 11 xylanase from Thermobacillus xylanilyticus (Tx-xyl). The results obtained provide new insight into the role of the loop in the glycosylation/deglycosylation catalytic cycle, and underline the key importance of the nature of the residue located at the tip of the thumb-loop. The effect of mutations predicted in silico has been validated by in vitro site-directed mutagenesis experiments. Overall, we propose a comprehensive model of Tx-xyl catalysis in terms of substrate and product dynamics by identifying the action of the thumb-loop motion during catalysis. PMID:24688637

Dynamics in microbial communities: Unraveling mechanisms to identify principles

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

Konopka, Allan; Lindemann, Stephen R.; Fredrickson, Jim K.

2015-07-01

Diversity begets higher order properties such as functional stability and robustness in microbial communities, but principles that inform conceptual (and eventually predictive) models of community dynamics are lacking. Recent work has shown that selection as well as dispersal and drift shape communities, but the mechanistic bases for assembly of communities and the forces that maintain their function in the face of environmental perturbation are not well understood. Conceptually, some interactions among community members could generate endogenous dynamics in composition, even in the absence of environmental changes. These endogenous dynamics are further perturbed by exogenous forcing factors to produce a richermore » network of community interactions, and it is this “system” that is the basis for higher order community properties. Elucidation of principles that follow from this conceptual model requires identifying the mechanisms that (a) optimize diversity within a community and (b) impart community stability. The network of interactions between organisms can be an important element by providing a buffer against disturbance beyond the effect of functional redundancy, as alternative pathways with different combinations of microbes can be recruited to fulfill specific functions.« less

Probing Molecular Mechanisms of the Hsp90 Chaperone: Biophysical Modeling Identifies Key Regulators of Functional Dynamics

PubMed Central

Dixit, Anshuman; Verkhivker, Gennady M.

2012-01-01

Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based “conformational selection” of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected residue clusters may be a rather general functional requirement encoded across molecular chaperones. The obtained insights may be useful in guiding discovery of allosteric Hsp90 inhibitors targeting protein interfaces with co-chaperones and protein binding clients. PMID:22624053

Aquaporin-4 Functionality and Virchow-Robin Space Water Dynamics: Physiological Model for Neurovascular Coupling and Glymphatic Flow

PubMed Central

Kwee, Ingrid L.

2017-01-01

The unique properties of brain capillary endothelium, critical in maintaining the blood-brain barrier (BBB) and restricting water permeability across the BBB, have important consequences on fluid hydrodynamics inside the BBB hereto inadequately recognized. Recent studies indicate that the mechanisms underlying brain water dynamics are distinct from systemic tissue water dynamics. Hydrostatic pressure created by the systolic force of the heart, essential for interstitial circulation and lymphatic flow in systemic circulation, is effectively impeded from propagating into the interstitial fluid inside the BBB by the tightly sealed endothelium of brain capillaries. Instead, fluid dynamics inside the BBB is realized by aquaporin-4 (AQP-4), the water channel that connects astrocyte cytoplasm and extracellular (interstitial) fluid. Brain interstitial fluid dynamics, and therefore AQP-4, are now recognized as essential for two unique functions, namely, neurovascular coupling and glymphatic flow, the brain equivalent of systemic lymphatics. PMID:28820467

Aquaporin-4 Functionality and Virchow-Robin Space Water Dynamics: Physiological Model for Neurovascular Coupling and Glymphatic Flow.

PubMed

Nakada, Tsutomu; Kwee, Ingrid L; Igarashi, Hironaka; Suzuki, Yuji

2017-08-18

The unique properties of brain capillary endothelium, critical in maintaining the blood-brain barrier (BBB) and restricting water permeability across the BBB, have important consequences on fluid hydrodynamics inside the BBB hereto inadequately recognized. Recent studies indicate that the mechanisms underlying brain water dynamics are distinct from systemic tissue water dynamics. Hydrostatic pressure created by the systolic force of the heart, essential for interstitial circulation and lymphatic flow in systemic circulation, is effectively impeded from propagating into the interstitial fluid inside the BBB by the tightly sealed endothelium of brain capillaries. Instead, fluid dynamics inside the BBB is realized by aquaporin-4 (AQP-4), the water channel that connects astrocyte cytoplasm and extracellular (interstitial) fluid. Brain interstitial fluid dynamics, and therefore AQP-4, are now recognized as essential for two unique functions, namely, neurovascular coupling and glymphatic flow, the brain equivalent of systemic lymphatics.

Water dynamics in protein hydration shells: the molecular origins of the dynamical perturbation.

PubMed

Fogarty, Aoife C; Laage, Damien

2014-07-17

Protein hydration shell dynamics play an important role in biochemical processes including protein folding, enzyme function, and molecular recognition. We present here a comparison of the reorientation dynamics of individual water molecules within the hydration shell of a series of globular proteins: acetylcholinesterase, subtilisin Carlsberg, lysozyme, and ubiquitin. Molecular dynamics simulations and analytical models are used to access site-resolved information on hydration shell dynamics and to elucidate the molecular origins of the dynamical perturbation of hydration shell water relative to bulk water. We show that all four proteins have very similar hydration shell dynamics, despite their wide range of sizes and functions, and differing secondary structures. We demonstrate that this arises from the similar local surface topology and surface chemical composition of the four proteins, and that such local factors alone are sufficient to rationalize the hydration shell dynamics. We propose that these conclusions can be generalized to a wide range of globular proteins. We also show that protein conformational fluctuations induce a dynamical heterogeneity within the hydration layer. We finally address the effect of confinement on hydration shell dynamics via a site-resolved analysis and connect our results to experiments via the calculation of two-dimensional infrared spectra.

Water Dynamics in Protein Hydration Shells: The Molecular Origins of the Dynamical Perturbation

PubMed Central

2014-01-01

Protein hydration shell dynamics play an important role in biochemical processes including protein folding, enzyme function, and molecular recognition. We present here a comparison of the reorientation dynamics of individual water molecules within the hydration shell of a series of globular proteins: acetylcholinesterase, subtilisin Carlsberg, lysozyme, and ubiquitin. Molecular dynamics simulations and analytical models are used to access site-resolved information on hydration shell dynamics and to elucidate the molecular origins of the dynamical perturbation of hydration shell water relative to bulk water. We show that all four proteins have very similar hydration shell dynamics, despite their wide range of sizes and functions, and differing secondary structures. We demonstrate that this arises from the similar local surface topology and surface chemical composition of the four proteins, and that such local factors alone are sufficient to rationalize the hydration shell dynamics. We propose that these conclusions can be generalized to a wide range of globular proteins. We also show that protein conformational fluctuations induce a dynamical heterogeneity within the hydration layer. We finally address the effect of confinement on hydration shell dynamics via a site-resolved analysis and connect our results to experiments via the calculation of two-dimensional infrared spectra. PMID:24479585

Functional Coping Dynamics and Experiential Avoidance in a Community Sample with No Self-Injury vs. Non-Suicidal Self-Injury Only vs. Those with Both Non-Suicidal Self-Injury and Suicidal Behaviour

PubMed Central

Nielsen, Emma; Sayal, Kapil; Townsend, Ellen

2017-01-01

Although emotional avoidance may be a critical factor in the pathway from psychological distress to self-injury and/or suicidality, little is known about the relative importance of differing functional coping dynamics and experiential avoidance between people with self-injury histories of differing intent (e.g., Non-Suicidal Self-Injury only vs. Non-Suicidal Self-Injury plus Suicidal Behaviour; NSSI vs. NSSI + SB). A community-based survey (N = 313; female, 81%; ages 16–49 years, M = 19.78, SD = 3.48) explored self-reported experiential avoidance and functional coping dynamics in individuals with (i) no self-injury history (controls); (ii) a history of NSSI only; and (iii) a history of NSSI + SB. Jonckheere-Terpstra trend tests indicated that avoidance coping was higher in the NSSI and NSSI + SB groups than in controls. Emotion regulation was higher in controls than those with a history of self-injury (NSSI and NSSI + SB). Approach and reappraisal coping demonstrated significant ordered effects such that control participants were higher in these coping dynamics than those with a history of NSSI only, who, in turn, were higher than those with a history of NSSI + SB (Control > NSSI > NSSI + SB). Endorsement of the reappraisal/denial facet of experiential avoidance was most pronounced in those with a history of NSSI + SB (Control < NSSI < NSSI + SB). No significant ordered effects were observed for other dimensions of experiential avoidance. Understanding how the endorsement of functional coping dynamics and which components of experiential avoidance vary between groups with differing self-injury intent histories has important implications for treatment planning. PMID:28555056

Functional Coping Dynamics and Experiential Avoidance in a Community Sample with No Self-Injury vs. Non-Suicidal Self-Injury Only vs. Those with Both Non-Suicidal Self-Injury and Suicidal Behaviour.

PubMed

Nielsen, Emma; Sayal, Kapil; Townsend, Ellen

2017-05-29

Although emotional avoidance may be a critical factor in the pathway from psychological distress to self-injury and/or suicidality, little is known about the relative importance of differing functional coping dynamics and experiential avoidance between people with self-injury histories of differing intent (e.g., Non-Suicidal Self-Injury only vs. Non-Suicidal Self-Injury plus Suicidal Behaviour; NSSI vs. NSSI + SB). A community-based survey (N = 313; female, 81%; ages 16-49 years, M = 19.78, SD = 3.48) explored self-reported experiential avoidance and functional coping dynamics in individuals with (i) no self-injury history (controls); (ii) a history of NSSI only; and (iii) a history of NSSI + SB. Jonckheere-Terpstra trend tests indicated that avoidance coping was higher in the NSSI and NSSI + SB groups than in controls. Emotion regulation was higher in controls than those with a history of self-injury (NSSI and NSSI + SB). Approach and reappraisal coping demonstrated significant ordered effects such that control participants were higher in these coping dynamics than those with a history of NSSI only, who, in turn, were higher than those with a history of NSSI + SB (Control > NSSI > NSSI + SB). Endorsement of the reappraisal/denial facet of experiential avoidance was most pronounced in those with a history of NSSI + SB (Control < NSSI < NSSI + SB). No significant ordered effects were observed for other dimensions of experiential avoidance. Understanding how the endorsement of functional coping dynamics and which components of experiential avoidance vary between groups with differing self-injury intent histories has important implications for treatment planning.

The resonant system: Linking brain-body-environment in sport performance☆.

PubMed

Teques, Pedro; Araújo, Duarte; Seifert, Ludovic; Del Campo, Vicente L; Davids, Keith

2017-01-01

The ecological dynamics approach offers new insights to understand how athlete nervous systems are embedded within the body-environment system in sport. Cognitive neuroscience focuses on the neural bases of athlete behaviors in terms of perceptual, cognitive, and motor functions defined within specific brain structures. Here, we discuss some limitations of this traditional perspective, addressing how athletes functionally adapt perception and action to the dynamics of complex performance environments by continuously perceiving information to regulate goal-directed actions. We examine how recent neurophysiological evidence of functioning in diverse cortical and subcortical regions appears more compatible with an ecological dynamics perspective, than traditional views in cognitive neuroscience. We propose how athlete behaviors in sports may be related to the tuning of resonant mechanisms indicating that perception is a dynamic process involving the whole body of the athlete. We emphasize the important role of metastable dynamics in the brain-body-environment system facilitating continuous interactions with a landscape of affordances (opportunities for action) in a performance environment. We discuss implications of these ideas for performance preparation and practice design in sport. © 2017 Elsevier B.V. All rights reserved.

Decomposition of Proteins into Dynamic Units from Atomic Cross-Correlation Functions.

PubMed

Calligari, Paolo; Gerolin, Marco; Abergel, Daniel; Polimeno, Antonino

2017-01-10

In this article, we present a clustering method of atoms in proteins based on the analysis of the correlation times of interatomic distance correlation functions computed from MD simulations. The goal is to provide a coarse-grained description of the protein in terms of fewer elements that can be treated as dynamically independent subunits. Importantly, this domain decomposition method does not take into account structural properties of the protein. Instead, the clustering of protein residues in terms of networks of dynamically correlated domains is defined on the basis of the effective correlation times of the pair distance correlation functions. For these properties, our method stands as a complementary analysis to the customary protein decomposition in terms of quasi-rigid, structure-based domains. Results obtained for a prototypal protein structure illustrate the approach proposed.

Histone chaperones: assisting histone traffic and nucleosome dynamics.

PubMed

Gurard-Levin, Zachary A; Quivy, Jean-Pierre; Almouzni, Geneviève

2014-01-01

The functional organization of eukaryotic DNA into chromatin uses histones as components of its building block, the nucleosome. Histone chaperones, which are proteins that escort histones throughout their cellular life, are key actors in all facets of histone metabolism; they regulate the supply and dynamics of histones at chromatin for its assembly and disassembly. Histone chaperones can also participate in the distribution of histone variants, thereby defining distinct chromatin landscapes of importance for genome function, stability, and cell identity. Here, we discuss our current knowledge of the known histone chaperones and their histone partners, focusing on histone H3 and its variants. We then place them into an escort network that distributes these histones in various deposition pathways. Through their distinct interfaces, we show how they affect dynamics during DNA replication, DNA damage, and transcription, and how they maintain genome integrity. Finally, we discuss the importance of histone chaperones during development and describe how misregulation of the histone flow can link to disease.

Epilogue: Dynamic Morphosyntax in Functional Discourse Grammar

ERIC Educational Resources Information Center

Velasco, Daniel Garcia; Hengeveld, Kees; Mackenzie, J. Lachlan

2012-01-01

This epilogue addresses the most important topics and challenges for the Morphosyntactic Level in Functional Discourse Grammar that have been raised in the articles in this Special Issue. We begin by exploring the differences between the Morphosyntactic Level in FDG and the treatment of morphosyntactic phenomena in other linguistic frameworks. We…

Structure and dynamics of aqueous solutions from PBE-based first-principles molecular dynamics simulations.

PubMed

Pham, Tuan Anh; Ogitsu, Tadashi; Lau, Edmond Y; Schwegler, Eric

2016-10-21

Establishing an accurate and predictive computational framework for the description of complex aqueous solutions is an ongoing challenge for density functional theory based first-principles molecular dynamics (FPMD) simulations. In this context, important advances have been made in recent years, including the development of sophisticated exchange-correlation functionals. On the other hand, simulations based on simple generalized gradient approximation (GGA) functionals remain an active field, particularly in the study of complex aqueous solutions due to a good balance between the accuracy, computational expense, and the applicability to a wide range of systems. Such simulations are often performed at elevated temperatures to artificially "correct" for GGA inaccuracies in the description of liquid water; however, a detailed understanding of how the choice of temperature affects the structure and dynamics of other components, such as solvated ions, is largely unknown. To address this question, we carried out a series of FPMD simulations at temperatures ranging from 300 to 460 K for liquid water and three representative aqueous solutions containing solvated Na + , K + , and Cl - ions. We show that simulations at 390-400 K with the Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional yield water structure and dynamics in good agreement with experiments at ambient conditions. Simultaneously, this computational setup provides ion solvation structures and ion effects on water dynamics consistent with experiments. Our results suggest that an elevated temperature around 390-400 K with the PBE functional can be used for the description of structural and dynamical properties of liquid water and complex solutions with solvated ions at ambient conditions.

In silico strategies toward enzyme function and dynamics.

PubMed

Estácio, Sílvia G

2012-01-01

Enzymes are outstanding biocatalysts involved in a plethora of chemical reactions occurring in the cell. Despite their incommensurable importance, a comprehensive understanding of enzyme catalysis is still missing. This task becomes more laborious given the unavoidability of including the inherent dynamic nature of enzymes into that description. As such, it is essential to ascertain the nature and contribution of enzyme conformational changes to catalysis and to evaluate the adequacy of the proposal associating protein internal motions to the rate enhancement achieved. Dynamic events in enzymes span a wide range of time- and length-scales which have led to a surge in multiscale methodologies targeting enzyme function and dynamics. Computational strategies assume a preponderant role in such studies by allowing the atomic detail investigation of the fundamental mechanisms of enzyme catalysis thus surpassing what is achievable through experiments. While high-accuracy quantum mechanical methods are indicated to uncover the details of the chemical reaction occurring at the active site, molecular mechanical force fields and molecular dynamics approaches provide powerful means to access the conformational energy landscape accessible to enzymes. This review outlines some of the most important in silico methodologies in this area, highlighting examples of problems tackled and the insights obtained. Copyright © 2012 Elsevier Inc. All rights reserved.

Ab initio theory and modeling of water.

PubMed

Chen, Mohan; Ko, Hsin-Yu; Remsing, Richard C; Calegari Andrade, Marcos F; Santra, Biswajit; Sun, Zhaoru; Selloni, Annabella; Car, Roberto; Klein, Michael L; Perdew, John P; Wu, Xifan

2017-10-10

Water is of the utmost importance for life and technology. However, a genuinely predictive ab initio model of water has eluded scientists. We demonstrate that a fully ab initio approach, relying on the strongly constrained and appropriately normed (SCAN) density functional, provides such a description of water. SCAN accurately describes the balance among covalent bonds, hydrogen bonds, and van der Waals interactions that dictates the structure and dynamics of liquid water. Notably, SCAN captures the density difference between water and ice I h at ambient conditions, as well as many important structural, electronic, and dynamic properties of liquid water. These successful predictions of the versatile SCAN functional open the gates to study complex processes in aqueous phase chemistry and the interactions of water with other materials in an efficient, accurate, and predictive, ab initio manner.

Ab initio theory and modeling of water

PubMed Central

Chen, Mohan; Ko, Hsin-Yu; Remsing, Richard C.; Calegari Andrade, Marcos F.; Santra, Biswajit; Sun, Zhaoru; Selloni, Annabella; Car, Roberto; Klein, Michael L.; Perdew, John P.; Wu, Xifan

2017-01-01

Water is of the utmost importance for life and technology. However, a genuinely predictive ab initio model of water has eluded scientists. We demonstrate that a fully ab initio approach, relying on the strongly constrained and appropriately normed (SCAN) density functional, provides such a description of water. SCAN accurately describes the balance among covalent bonds, hydrogen bonds, and van der Waals interactions that dictates the structure and dynamics of liquid water. Notably, SCAN captures the density difference between water and ice Ih at ambient conditions, as well as many important structural, electronic, and dynamic properties of liquid water. These successful predictions of the versatile SCAN functional open the gates to study complex processes in aqueous phase chemistry and the interactions of water with other materials in an efficient, accurate, and predictive, ab initio manner. PMID:28973868

Complex systems dynamics in aging: new evidence, continuing questions.

PubMed

Cohen, Alan A

2016-02-01

There have long been suggestions that aging is tightly linked to the complex dynamics of the physiological systems that maintain homeostasis, and in particular to dysregulation of regulatory networks of molecules. This review synthesizes recent work that is starting to provide evidence for the importance of such complex systems dynamics in aging. There is now clear evidence that physiological dysregulation--the gradual breakdown in the capacity of complex regulatory networks to maintain homeostasis--is an emergent property of these regulatory networks, and that it plays an important role in aging. It can be measured simply using small numbers of biomarkers. Additionally, there are indications of the importance during aging of emergent physiological processes, functional processes that cannot be easily understood through clear metabolic pathways, but can nonetheless be precisely quantified and studied. The overall role of such complex systems dynamics in aging remains an important open question, and to understand it future studies will need to distinguish and integrate related aspects of aging research, including multi-factorial theories of aging, systems biology, bioinformatics, network approaches, robustness, and loss of complexity.

Emergence of rich-club topology and coordinated dynamics in development of hippocampal functional networks in vitro.

PubMed

Schroeter, Manuel S; Charlesworth, Paul; Kitzbichler, Manfred G; Paulsen, Ole; Bullmore, Edward T

2015-04-08

Recent studies demonstrated that the anatomical network of the human brain shows a "rich-club" organization. This complex topological feature implies that highly connected regions, hubs of the large-scale brain network, are more densely interconnected with each other than expected by chance. Rich-club nodes were traversed by a majority of short paths between peripheral regions, underlining their potential importance for efficient global exchange of information between functionally specialized areas of the brain. Network hubs have also been described at the microscale of brain connectivity (so-called "hub neurons"). Their role in shaping synchronous dynamics and forming microcircuit wiring during development, however, is not yet fully understood. The present study aimed to investigate the role of hubs during network development, using multi-electrode arrays and functional connectivity analysis during spontaneous multi-unit activity (MUA) of dissociated primary mouse hippocampal neurons. Over the first 4 weeks in vitro, functional connectivity significantly increased in strength, density, and size, with mature networks demonstrating a robust modular and small-world topology. As expected by a "rich-get-richer" growth rule of network evolution, MUA graphs were found to form rich-clubs at an early stage in development (14 DIV). Later on, rich-club nodes were a consistent topological feature of MUA graphs, demonstrating high nodal strength, efficiency, and centrality. Rich-club nodes were also found to be crucial for MUA dynamics. They often served as broker of spontaneous activity flow, confirming that hub nodes and rich-clubs may play an important role in coordinating functional dynamics at the microcircuit level. Copyright © 2015 the authors 0270-6474/15/355459-12$15.00/0.

From Sequence and Forces to Structure, Function and Evolution of Intrinsically Disordered Proteins

PubMed Central

Forman-Kay, Julie D.; Mittag, Tanja

2015-01-01

Intrinsically disordered proteins (IDPs), which lack persistent structure, are a challenge to structural biology due to the inapplicability of standard methods for characterization of folded proteins as well as their deviation from the dominant structure/function paradigm. Their widespread presence and involvement in biological function, however, has spurred the growing acceptance of the importance of IDPs and the development of new tools for studying their structure, dynamics and function. The interplay of folded and disordered domains or regions for function and the existence of a continuum of protein states with respect to conformational energetics, motional timescales and compactness is shaping a unified understanding of structure-dynamics-disorder/function relationships. On the 20th anniversary of this journal, Structure, we provide a historical perspective on the investigation of IDPs and summarize the sequence features and physical forces that underlie their unique structural, functional and evolutionary properties. PMID:24010708

From sequence and forces to structure, function, and evolution of intrinsically disordered proteins.

PubMed

Forman-Kay, Julie D; Mittag, Tanja

2013-09-03

Intrinsically disordered proteins (IDPs), which lack persistent structure, are a challenge to structural biology due to the inapplicability of standard methods for characterization of folded proteins as well as their deviation from the dominant structure/function paradigm. Their widespread presence and involvement in biological function, however, has spurred the growing acceptance of the importance of IDPs and the development of new tools for studying their structure, dynamics, and function. The interplay of folded and disordered domains or regions for function and the existence of a continuum of protein states with respect to conformational energetics, motional timescales, and compactness are shaping a unified understanding of structure-dynamics-disorder/function relationships. In the 20(th) anniversary of Structure, we provide a historical perspective on the investigation of IDPs and summarize the sequence features and physical forces that underlie their unique structural, functional, and evolutionary properties. Copyright © 2013 Elsevier Ltd. All rights reserved.

How to Express C++ Concepts in Fortran90

NASA Technical Reports Server (NTRS)

Decyk, V.; Norton, C.; Szymanski, B.

1997-01-01

r summarizes techniques for emulating in Fortran90 the most important object-oriented concepts of C++ classes (including abstract data types, encapsulation and function overloading), inheritance and dynamic dispatching.

How to Express C++ Concepts in Fortran90

DOE PAGES

Decyk, Viktor K.; Norton, Charles D.; Szymanski, Boleslaw K.

1997-01-01

This paper summarizes techniques for emulating in Fortran90 the most important objectoriented concepts of C++: classes (including abstract data types, encapsulation and function overloading), inheritance and dynamic dispatching.

Nonadditive effects of leaf litter species diversity on breakdown dynamics in a deteritus-bases stream

Treesearch

J.S. Kominoski; C.M. Pringle; B.A. Ball; M.A. Bradford; D.C. Coleman; D.B. Hall; M.D. Hunter

2007-01-01

Since species loss is predicted to be nonrandom, it is important to understand the manner in which those species that we anticipate losing interact with other species to affect ecosystem function. We tested whether litter species diversity, measured as richness and composition, affects breakdown dynamics in a detritus-based stream. Using full-factorial analyses of...

Conformational dynamics is key to understanding loss-of-function of NQO1 cancer-associated polymorphisms and its correction by pharmacological ligands

NASA Astrophysics Data System (ADS)

Encarnación, Medina-Carmona; Palomino-Morales, Rogelio J.; Fuchs, Julian E.; Esperanza, Padín-Gonzalez; Noel, Mesa-Torres; Salido, Eduardo; Timson, David J.; Pey, Angel L.

2016-02-01

Protein dynamics is essential to understand protein function and stability, even though is rarely investigated as the origin of loss-of-function due to genetic variations. Here, we use biochemical, biophysical, cell and computational biology tools to study two loss-of-function and cancer-associated polymorphisms (p.R139W and p.P187S) in human NAD(P)H quinone oxidoreductase 1 (NQO1), a FAD-dependent enzyme which activates cancer pro-drugs and stabilizes several oncosuppressors. We show that p.P187S strongly destabilizes the NQO1 dimer in vitro and increases the flexibility of the C-terminal domain, while a combination of FAD and the inhibitor dicoumarol overcome these alterations. Additionally, changes in global stability due to polymorphisms and ligand binding are linked to the dynamics of the dimer interface, whereas the low activity and affinity for FAD in p.P187S is caused by increased fluctuations at the FAD binding site. Importantly, NQO1 steady-state protein levels in cell cultures correlate primarily with the dynamics of the C-terminal domain, supporting a directional preference in NQO1 proteasomal degradation and the use of ligands binding to this domain to stabilize p.P187S in vivo. In conclusion, protein dynamics are fundamental to understanding loss-of-function in p.P187S, and to develop new pharmacological therapies to rescue this function.

Overreaching in coordination dynamics therapy in an athlete with a spinal cord injury.

PubMed

Schalow, G; Vaher, I; Jaigma, P

2008-03-01

A motocross athlete suffered a clinically complete spinal cord injury (SCI) during competition. Although MRIs (magnetic resonance imaging) showed a complete spinal cord injury at the Thoracic 11/12 levels, surface EMG recordings indicated the survival of few tract fibres across the injury site. Six weeks after the accident the subject began intensive Coordination Dynamics Therapy (CDT) at an up-to-date therapy centre. The subject trained at his physical limits to induce structural and functional repair. Exercising at variable loads between 20 and 200N (on a special CDT and recording device) generated periods of overreaching and super-compensation. By plotting coordination dynamics values (kinesiology), including high-load exertion (200N) and hysteresis curves, periods of overreaching and super-compensation were made graphically visible. It was found that symmetrical improvements of central nervous system (CNS) functioning occurred during overreaching. Improvements in spinal cord functioning were achieved throughout one year of CDT in this chronically injured subject with an almost anatomically complete SCI. It is discussed that the measuring of CNS functions by means of recording coordination dynamics is a powerful and non-invasive tool ideal for exact quantitative and qualitative measurements of improvement (or change) in CNS functioning. Such diagnostics may be of particular importance in sport during training and before competition. Also, coordination dynamics might be used to measure the effects of prolonged exposure to reduced gravitational conditions on CNS functions, such as faced by astronauts.

Comparison of SH3 and SH2 domain dynamics when expressed alone or in an SH(3+2) construct: the role of protein dynamics in functional regulation.

PubMed

Engen, J R; Smithgall, T E; Gmeiner, W H; Smith, D L

1999-04-02

Protein dynamics play an important role in protein function and regulation of enzymatic activity. To determine how additional interactions with surrounding structure affects local protein dynamics, we have used hydrogen exchange and mass spectrometry to investigate the SH2 and SH3 domains of the protein tyrosine kinase Hck. Exchange rates of isolated Hck SH3 and SH2 domains were compared with rates for the same domains when part of a larger SH(3+2) construct. Increased deuterium incorporation was observed for the SH3 domain in the joint construct, particularly near the SH2 interface and the short sequence that connects SH3 to SH2, implying greater flexibility of SH3 when it is part of SH(3+2). Slow cooperative unfolding of the SH3 domain occurred at the same rate in isolated SH3 as in the SH(3+2) construct, suggesting a functional significance for this unfolding. The SH2 domain displayed relatively smaller changes in flexibility when part of the SH(3+2) construct. These results suggest that the domains influence each other. Further, our results imply a link between functional regulation and structural dynamics of SH3 and SH2 domains. Copyright 1999 Academic Press.

Loop-loop interactions govern multiple steps in indole-3-glycerol phosphate synthase catalysis

PubMed Central

Zaccardi, Margot J; O'Rourke, Kathleen F; Yezdimer, Eric M; Loggia, Laura J; Woldt, Svenja; Boehr, David D

2014-01-01

Substrate binding, product release, and likely chemical catalysis in the tryptophan biosynthetic enzyme indole-3-glycerol phosphate synthase (IGPS) are dependent on the structural dynamics of the β1α1 active-site loop. Statistical coupling analysis and molecular dynamic simulations had previously indicated that covarying residues in the β1α1 and β2α2 loops, corresponding to Arg54 and Asn90, respectively, in the Sulfolobus sulfataricus enzyme (ssIGPS), are likely important for coordinating functional motions of these loops. To test this hypothesis, we characterized site mutants at these positions for changes in catalytic function, protein stability and structural dynamics for the thermophilic ssIGPS enzyme. Although there were only modest changes in the overall steady-state kinetic parameters, solvent viscosity and solvent deuterium kinetic isotope effects indicated that these amino acid substitutions change the identity of the rate-determining step across multiple temperatures. Surprisingly, the N90A substitution had a dramatic effect on the general acid/base catalysis of the dehydration step, as indicated by the loss of the descending limb in the pH rate profile, which we had previously assigned to Lys53 on the β1α1 loop. These changes in enzyme function are accompanied with a quenching of ps-ns and µs-ms timescale motions in the β1α1 loop as measured by nuclear magnetic resonance studies. Altogether, our studies provide structural, dynamic and functional rationales for the coevolution of residues on the β1α1 and β2α2 loops, and highlight the multiple roles that the β1α1 loop plays in IGPS catalysis. Thus, substitution of covarying residues in the active-site β1α1 and β2α2 loops of indole-3-glycerol phosphate synthase results in functional, structural, and dynamic changes, highlighting the multiple roles that the β1α1 loop plays in enzyme catalysis and the importance of regulating the structural dynamics of this loop through noncovalent interactions with nearby structural elements. PMID:24403092

An extended view of nuclear lamin structure, function, and dynamics.

PubMed

Paddy, M R; Agard, D A; Sedat, J W

1992-08-01

Molecularly-based studies of nuclear lamins have progressed at a rapid rate in the last decade. However, we still have no answer to the most important question: what are the functions of lamins? In this review we describe recent experiments which challenge traditional views of lamin function and structure. These surprising results indicate that much lamin functionality remains to be discovered, and that more global approaches to lamin structure and function are especially appropriate at this time.

ACF7 regulates cytoskeletal-focal adhesion dynamics and migration and has ATPase activity.

PubMed

Wu, Xiaoyang; Kodama, Atsuko; Fuchs, Elaine

2008-10-03

Coordinated interactions between microtubule (MT) and actin cytoskeletons are involved in many polarized cellular processes. Spectraplakins are enormous (>500 kDa) proteins able to bind both MTs and actin filaments (F-actin) directly. To elucidate the physiological significance and functions of mammalian spectraplakin ACF7, we've conditionally targeted it in skin epidermis. Intriguingly, ACF7 deficiency compromises the targeting of microtubules along F-actin to focal adhesions (FAs), stabilizes FA-actin networks, and impairs epidermal migration. Exploring underlying mechanisms, we show that ACF7's binding domains for F-actin, MTs, and MT plus-end proteins are not sufficient to rescue the defects in FA-cytoskeletal dynamics and migration functions of ACF7 null keratinocytes. We've uncovered an intrinsic actin-regulated ATPase domain in ACF7 and demonstrate that it is both functional and essential for these roles. Our findings provide insight into the functions of this important cytoskeletal crosslinking protein in regulating dynamic interactions between MTs and F-actin to sustain directional cell movement.

Evolution of intrinsic disorder in eukaryotic proteins.

PubMed

Ahrens, Joseph B; Nunez-Castilla, Janelle; Siltberg-Liberles, Jessica

2017-09-01

Conformational flexibility conferred though regions of intrinsic structural disorder allows proteins to behave as dynamic molecules. While it is well-known that intrinsically disordered regions can undergo disorder-to-order transitions in real-time as part of their function, we also are beginning to learn more about the dynamics of disorder-to-order transitions along evolutionary time-scales. Intrinsically disordered regions endow proteins with functional promiscuity, which is further enhanced by the ability of some of these regions to undergo real-time disorder-to-order transitions. Disorder content affects gene retention after whole genome duplication, but it is not necessarily conserved. Altered patterns of disorder resulting from evolutionary disorder-to-order transitions indicate that disorder evolves to modify function through refining stability, regulation, and interactions. Here, we review the evolution of intrinsically disordered regions in eukaryotic proteins. We discuss the interplay between secondary structure and disorder on evolutionary time-scales, the importance of disorder for eukaryotic proteome expansion and functional divergence, and the evolutionary dynamics of disorder.

All-atom molecular dynamics of the HBV capsid reveals insights into biological function and cryo-EM resolution limits

PubMed Central

Perilla, Juan R; Schlicksup, Christopher John; Venkatakrishnan, Balasubramanian; Zlotnick, Adam; Schulten, Klaus

2018-01-01

The hepatitis B virus capsid represents a promising therapeutic target. Experiments suggest the capsid must be flexible to function; however, capsid structure and dynamics have not been thoroughly characterized in the absence of icosahedral symmetry constraints. Here, all-atom molecular dynamics simulations are leveraged to investigate the capsid without symmetry bias, enabling study of capsid flexibility and its implications for biological function and cryo-EM resolution limits. Simulation results confirm flexibility and reveal a propensity for asymmetric distortion. The capsid’s influence on ionic species suggests a mechanism for modulating the display of cellular signals and implicates the capsid’s triangular pores as the location of signal exposure. A theoretical image reconstruction performed using simulated conformations indicates how capsid flexibility may limit the resolution of cryo-EM. Overall, the present work provides functional insight beyond what is accessible to experimental methods and raises important considerations regarding asymmetry in structural studies of icosahedral virus capsids. PMID:29708495

Evol and ProDy for bridging protein sequence evolution and structural dynamics

PubMed Central

Mao, Wenzhi; Liu, Ying; Chennubhotla, Chakra; Lezon, Timothy R.; Bahar, Ivet

2014-01-01

Correlations between sequence evolution and structural dynamics are of utmost importance in understanding the molecular mechanisms of function and their evolution. We have integrated Evol, a new package for fast and efficient comparative analysis of evolutionary patterns and conformational dynamics, into ProDy, a computational toolbox designed for inferring protein dynamics from experimental and theoretical data. Using information-theoretic approaches, Evol coanalyzes conservation and coevolution profiles extracted from multiple sequence alignments of protein families with their inferred dynamics. Availability and implementation: ProDy and Evol are open-source and freely available under MIT License from http://prody.csb.pitt.edu/. Contact: bahar@pitt.edu PMID:24849577

[Review of dynamic global vegetation models (DGVMs)].

PubMed

Che, Ming-Liang; Chen, Bao-Zhang; Wang, Ying; Guo, Xiang-Yun

2014-01-01

Dynamic global vegetation model (DGVM) is an important and efficient tool for study on the terrestrial carbon circle processes and vegetation dynamics. This paper reviewed the development history of DGVMs, introduced the basic structure of DGVMs, and the outlines of several world-widely used DGVMs, including CLM-DGVM, LPJ, IBIS and SEIB. The shortages of the description of dynamic vegetation mechanisms in the current DGVMs were proposed, including plant functional types (PFT) scheme, vegetation competition, disturbance, and phenology. Then the future research directions of DGVMs were pointed out, i. e. improving the PFT scheme, refining the vegetation dynamic mechanism, and implementing a model inter-comparison project.

Ionospheric Outflow in the Magnetosphere: Circulation and Consequences

NASA Astrophysics Data System (ADS)

Welling, D. T.; Liemohn, M. W.

2017-12-01

Including ionospheric outflow in global magnetohydrodynamic models of near-Earth outer space has become an important step towards understanding the role of this plasma source in the magnetosphere. Such simulations have revealed the importance of outflow in populating the plasma sheet and inner magnetosphere as a function of outflow source characteristics. More importantly, these experiments have shown how outflow can control global dynamics, including tail dynamics and dayside reconnection rate. The broad impact of light and heavy ion outflow can create non-linear feedback loops between outflow and the magnetosphere. This paper reviews some of the most important revelations from global magnetospheric modeling that includes ionospheric outflow of light and heavy ions. It also introduces new advances in outflow modeling and coupling outflow to the magnetosphere.

Quantum Critical Point revisited by the Dynamical Mean Field Theory

NASA Astrophysics Data System (ADS)

Xu, Wenhu; Kotliar, Gabriel; Tsvelik, Alexei

Dynamical mean field theory is used to study the quantum critical point (QCP) in the doped Hubbard model on a square lattice. The QCP is characterized by a universal scaling form of the self energy and a spin density wave instability at an incommensurate wave vector. The scaling form unifies the low energy kink and the high energy waterfall feature in the spectral function, while the spin dynamics includes both the critical incommensurate and high energy antiferromagnetic paramagnons. We use the frequency dependent four-point correlation function of spin operators to calculate the momentum dependent correction to the electron self energy. Our results reveal a substantial difference with the calculations based on the Spin-Fermion model which indicates that the frequency dependence of the the quasiparitcle-paramagnon vertices is an important factor. The authors are supported by Center for Computational Design of Functional Strongly Correlated Materials and Theoretical Spectroscopy under DOE Grant DE-FOA-0001276.

Principles of dynamical modularity in biological regulatory networks

PubMed Central

Deritei, Dávid; Aird, William C.; Ercsey-Ravasz, Mária; Regan, Erzsébet Ravasz

2016-01-01

Intractable diseases such as cancer are associated with breakdown in multiple individual functions, which conspire to create unhealthy phenotype-combinations. An important challenge is to decipher how these functions are coordinated in health and disease. We approach this by drawing on dynamical systems theory. We posit that distinct phenotype-combinations are generated by interactions among robust regulatory switches, each in control of a discrete set of phenotypic outcomes. First, we demonstrate the advantage of characterizing multi-switch regulatory systems in terms of their constituent switches by building a multiswitch cell cycle model which points to novel, testable interactions critical for early G2/M commitment to division. Second, we define quantitative measures of dynamical modularity, namely that global cell states are discrete combinations of switch-level phenotypes. Finally, we formulate three general principles that govern the way coupled switches coordinate their function. PMID:26979940

The Language, Tone and Prosody of Emotions: Neural Substrates and Dynamics of Spoken-Word Emotion Perception

PubMed Central

Liebenthal, Einat; Silbersweig, David A.; Stern, Emily

2016-01-01

Rapid assessment of emotions is important for detecting and prioritizing salient input. Emotions are conveyed in spoken words via verbal and non-verbal channels that are mutually informative and unveil in parallel over time, but the neural dynamics and interactions of these processes are not well understood. In this paper, we review the literature on emotion perception in faces, written words, and voices, as a basis for understanding the functional organization of emotion perception in spoken words. The characteristics of visual and auditory routes to the amygdala—a subcortical center for emotion perception—are compared across these stimulus classes in terms of neural dynamics, hemispheric lateralization, and functionality. Converging results from neuroimaging, electrophysiological, and lesion studies suggest the existence of an afferent route to the amygdala and primary visual cortex for fast and subliminal processing of coarse emotional face cues. We suggest that a fast route to the amygdala may also function for brief non-verbal vocalizations (e.g., laugh, cry), in which emotional category is conveyed effectively by voice tone and intensity. However, emotional prosody which evolves on longer time scales and is conveyed by fine-grained spectral cues appears to be processed via a slower, indirect cortical route. For verbal emotional content, the bulk of current evidence, indicating predominant left lateralization of the amygdala response and timing of emotional effects attributable to speeded lexical access, is more consistent with an indirect cortical route to the amygdala. Top-down linguistic modulation may play an important role for prioritized perception of emotions in words. Understanding the neural dynamics and interactions of emotion and language perception is important for selecting potent stimuli and devising effective training and/or treatment approaches for the alleviation of emotional dysfunction across a range of neuropsychiatric states. PMID:27877106

The Language, Tone and Prosody of Emotions: Neural Substrates and Dynamics of Spoken-Word Emotion Perception.

PubMed

Liebenthal, Einat; Silbersweig, David A; Stern, Emily

2016-01-01

Rapid assessment of emotions is important for detecting and prioritizing salient input. Emotions are conveyed in spoken words via verbal and non-verbal channels that are mutually informative and unveil in parallel over time, but the neural dynamics and interactions of these processes are not well understood. In this paper, we review the literature on emotion perception in faces, written words, and voices, as a basis for understanding the functional organization of emotion perception in spoken words. The characteristics of visual and auditory routes to the amygdala-a subcortical center for emotion perception-are compared across these stimulus classes in terms of neural dynamics, hemispheric lateralization, and functionality. Converging results from neuroimaging, electrophysiological, and lesion studies suggest the existence of an afferent route to the amygdala and primary visual cortex for fast and subliminal processing of coarse emotional face cues. We suggest that a fast route to the amygdala may also function for brief non-verbal vocalizations (e.g., laugh, cry), in which emotional category is conveyed effectively by voice tone and intensity. However, emotional prosody which evolves on longer time scales and is conveyed by fine-grained spectral cues appears to be processed via a slower, indirect cortical route. For verbal emotional content, the bulk of current evidence, indicating predominant left lateralization of the amygdala response and timing of emotional effects attributable to speeded lexical access, is more consistent with an indirect cortical route to the amygdala. Top-down linguistic modulation may play an important role for prioritized perception of emotions in words. Understanding the neural dynamics and interactions of emotion and language perception is important for selecting potent stimuli and devising effective training and/or treatment approaches for the alleviation of emotional dysfunction across a range of neuropsychiatric states.

How Language Learners Can Improve Their Emotional Functioning: Important Psychological and Psychospiritual Theories

ERIC Educational Resources Information Center

Oxford, Rebecca L.

2015-01-01

Emotion is "the primary human motive" (MacIntyre, 2002, p. 61). The human brain is an emotional brain, creating relationships among thought, emotion, and motivation in a complex dynamic system (Dörnyei, 2009). Emotion "functions as an amplifier, providing the intensity, urgency, and energy to propel our behavior" in…

An experimental analysis of granivory in a desert ecosystem: Progress report

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

Brown, J.H.

1987-03-01

Controlled, replicated experiments are revealing the network of interactions that determine structure, dynamics, and energy transfer in a desert community that is functionally interconnected by the consumption of seeds (granivory). This community includes seed-eating rodents, ants, and birds, seed-producing annual and perennial plants, and other kinds of organisms that interact with these. The experiments entail removal of important species or functional groups of granivores or plants and supplementation of seed resources. The results demonstrate a large number of direct and indirect interactions that have important effects on the abundance of species and functional groups, the structure of the community, andmore » the dynamics of energy flow. The results suggest that networks of interaction are structured with sufficient overlap in resource requirements and interconnections through indirect pathways that community- and ecosystem-level processes, such as energy flow, are relatively insensitive to major perturbations in the abundance of particular species or functional groups. This preliminary finding has important implications for understanding the response of ecosystems to natural and human-caused perturbations, for the management of agricultural and other human-modified ecosystems, and for the design of perturbation-resistant networks for acquisition and distribution of human resources such energy and information. 44 refs.« less

Developmental improvements in dynamic control of fingertip forces last throughout childhood and into adolescence

PubMed Central

Dayanidhi, Sudarshan; Hedberg, Åsa; Forssberg, Hans

2013-01-01

While it is clear that the development of dexterous manipulation in children exhibits dramatic improvements over an extended period, it is difficult to separate musculoskeletal from neural contributors to these important functional gains. This is in part due to the inability of current methods to disambiguate improvements in hand strength from gains in finger dexterity (i.e., the dynamic control of fingertip force vectors at low magnitudes). We adapted our novel instrumentation to evaluate finger dexterity in 130 typically developing children between the ages of 4 and 16 yr. We find that finger dexterity continues to develop well into late adolescence and musculoskeletal growth and strength are poorly correlated with the improvements in dexterity. Importantly, because these behavioral results seem to mirror the known timelines of neuroanatomical development up to adolescence, we speculate that they reflect the functional benefits of such continual neural maturation. This novel perspective now enables the systematic study of the functional roles of specific neuroanatomical structures and their connectivity, maturity, and plasticity. Moreover, the temporal dynamics of the fingertip force vectors shows improvements in stability that provide a novel way to look at the maturation of finger control. From a clinical perspective, our results provide a practical means to chart functional development of dexterous manipulation in typically developing children and could be adapted for clinical use and for use in children with developmental disorders. PMID:23864371

Multiple effects of hydrological connectivity on floodplain processes in human modified river systems

NASA Astrophysics Data System (ADS)

Hein, Thomas; Bondar-Kunze, Elisabeth; Preiner, Stefan; Reckendorfer, Walter; Tritthart, Michael; Weigelhofer, Gabriele; Welti, Nina

2014-05-01

Floodplain and riparian ecosystems provide multiple functions and services of importance for human well-being and are of strategic importance for different sectors at catchment scale. Especially floodplains in the vicinity of urban areas can be areas of conflicting interests ranging from different land use types, flood water retention, drinking water production and recreation to conservation of last remnants of former riverine landscape, as it is the case in floodplains in the Danube Nationalpark downstream Vienna. Many of these ecosystem functions and services are controlled by the exchange conditions between river main channel and floodplain systems, the hydrological connectivity. At the same time these systems have been highly altered and especially the connectivity has been severely impaired. Thus, far ranging effects of changes in hydrological connectivity at various levels can be expected in altered floodplain systems. The aim of this presentation is to explore the complex control of different ecosystem functions and associated services by different parameters of hydrological connectivity, ranging from nutrient, sediment and matter dynamics and biodiversity aspects. Increasing connectivity will be shown to impact microbial dynamics, sediment-water interactions, carbon dynamics and trophic conditions, thus affecting the fundamental functions of particular floodplain systems at various spatial and temporal scales. Based on these changes also the provision of ecosystem services of floodplains is affected. The results clearly show that hydrological connectivity needs to be considered in a sustainable management approach.

Dynamics of active sites in biological macromolecules using a Green-function approach: An application to heme vibrational dynamics in myoglobin

NASA Astrophysics Data System (ADS)

Rai, Brajesh; Prohofsky, Earl

2003-03-01

Dynamics of functionally active regions of biological macromolecules can be studied using a Green-function technique. This approach uses the fact that in most cases one has a good set of force constants for active sites, and rather poorly defined force field parameters for other regions of the macromolecule. The Green-function method is applied to study the iron vibrational modes of the heme active site in myoglobin. In this approach, the heme active site is viewed as a system interacting with surrounding globin, which acts as an excitation bath. The normal modes of heme and globin are separately calculated using the best available force fields for the two entities. The iron vibrational spectrum of myoglobin is then obtained using the solutions of the heme and globin, and by considering physically meaningful interactions between the two units. The refinement of the Green-function calculations to the experimental data from an x-ray synchrotron-based Nuclear Resonance Vibrational Spectroscopy provides important insights into the character of iron normal modes of myoglobin.

Self-consistent Green's function embedding for advanced electronic structure methods based on a dynamical mean-field concept

NASA Astrophysics Data System (ADS)

Chibani, Wael; Ren, Xinguo; Scheffler, Matthias; Rinke, Patrick

2016-04-01

We present an embedding scheme for periodic systems that facilitates the treatment of the physically important part (here a unit cell or a supercell) with advanced electronic structure methods, that are computationally too expensive for periodic systems. The rest of the periodic system is treated with computationally less demanding approaches, e.g., Kohn-Sham density-functional theory, in a self-consistent manner. Our scheme is based on the concept of dynamical mean-field theory formulated in terms of Green's functions. Our real-space dynamical mean-field embedding scheme features two nested Dyson equations, one for the embedded cluster and another for the periodic surrounding. The total energy is computed from the resulting Green's functions. The performance of our scheme is demonstrated by treating the embedded region with hybrid functionals and many-body perturbation theory in the GW approach for simple bulk systems. The total energy and the density of states converge rapidly with respect to the computational parameters and approach their bulk limit with increasing cluster (i.e., computational supercell) size.

Fixation, transient landscape, and diffusion dilemma in stochastic evolutionary game dynamics

NASA Astrophysics Data System (ADS)

Zhou, Da; Qian, Hong

2011-09-01

Agent-based stochastic models for finite populations have recently received much attention in the game theory of evolutionary dynamics. Both the ultimate fixation and the pre-fixation transient behavior are important to a full understanding of the dynamics. In this paper, we study the transient dynamics of the well-mixed Moran process through constructing a landscape function. It is shown that the landscape playing a central theoretical “device” that integrates several lines of inquiries: the stable behavior of the replicator dynamics, the long-time fixation, and continuous diffusion approximation associated with asymptotically large population. Several issues relating to the transient dynamics are discussed: (i) multiple time scales phenomenon associated with intra- and inter-attractoral dynamics; (ii) discontinuous transition in stochastically stationary process akin to Maxwell construction in equilibrium statistical physics; and (iii) the dilemma diffusion approximation facing as a continuous approximation of the discrete evolutionary dynamics. It is found that rare events with exponentially small probabilities, corresponding to the uphill movements and barrier crossing in the landscape with multiple wells that are made possible by strong nonlinear dynamics, plays an important role in understanding the origin of the complexity in evolutionary, nonlinear biological systems.

Super-resolution microscopy reveals structural diversity in molecular exchange among peptide amphiphile nanofibres

DOE PAGES

da Silva, Ricardo M. P.; van der Zwaag, Daan; Albertazzi, Lorenzo; ...

2016-05-19

The dynamic behaviour of supramolecular systems is an important dimension of their potential functions. Here, we report on the use of stochastic optical reconstruction microscopy to study the molecular exchange of peptide amphiphile nanofibres, supramolecular systems known to have important biomedical functions. Solutions of nanofibres labelled with different dyes (Cy3 and Cy5) were mixed, and the distribution of dyes inserting into initially single-colour nanofibres was quantified using correlative image analysis. Our observations are consistent with an exchange mechanism involving monomers or small clusters of molecules inserting randomly into a fibre. Different exchange rates are observed within the same fibre, suggestingmore » that local cohesive structures exist on the basis of beta-sheet discontinuous domains. The results reported here show that peptide amphiphile supramolecular systems can be dynamic and that their intermolecular interactions affect exchange patterns. Lastly, this information can be used to generate useful aggregate morphologies for improved biomedical function.« less

Functionalized anatomical models for EM-neuron Interaction modeling

NASA Astrophysics Data System (ADS)

Neufeld, Esra; Cassará, Antonino Mario; Montanaro, Hazael; Kuster, Niels; Kainz, Wolfgang

2016-06-01

The understanding of interactions between electromagnetic (EM) fields and nerves are crucial in contexts ranging from therapeutic neurostimulation to low frequency EM exposure safety. To properly consider the impact of in vivo induced field inhomogeneity on non-linear neuronal dynamics, coupled EM-neuronal dynamics modeling is required. For that purpose, novel functionalized computable human phantoms have been developed. Their implementation and the systematic verification of the integrated anisotropic quasi-static EM solver and neuronal dynamics modeling functionality, based on the method of manufactured solutions and numerical reference data, is described. Electric and magnetic stimulation of the ulnar and sciatic nerve were modeled to help understanding a range of controversial issues related to the magnitude and optimal determination of strength-duration (SD) time constants. The results indicate the importance of considering the stimulation-specific inhomogeneous field distributions (especially at tissue interfaces), realistic models of non-linear neuronal dynamics, very short pulses, and suitable SD extrapolation models. These results and the functionalized computable phantom will influence and support the development of safe and effective neuroprosthetic devices and novel electroceuticals. Furthermore they will assist the evaluation of existing low frequency exposure standards for the entire population under all exposure conditions.

First-principles quantum-mechanical investigations of biomass conversion at the liquid-solid interfaces

NASA Astrophysics Data System (ADS)

Dang, Hongli; Xue, Wenhua; Liu, Yingdi; Jentoft, Friederike; Resasco, Daniel; Wang, Sanwu

2014-03-01

We report first-principles density-functional calculations and ab initio molecular dynamics (MD) simulations for the reactions involving furfural, which is an important intermediate in biomass conversion, at the catalytic liquid-solid interfaces. The different dynamic processes of furfural at the water-Cu(111) and water-Pd(111) interfaces suggest different catalytic reaction mechanisms for the conversion of furfural. Simulations for the dynamic processes with and without hydrogen demonstrate the importance of the liquid-solid interface as well as the presence of hydrogen in possible catalytic reactions including hydrogenation and decarbonylation of furfural. Supported by DOE (DE-SC0004600). This research used the supercomputer resources of the XSEDE, the NERSC Center, and the Tandy Supercomputing Center.

Structure and dynamics of aqueous solutions from PBE-based first-principles molecular dynamics simulations

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

Pham, Tuan Anh; Ogitsu, Tadashi; Lau, Edmond Y.

Establishing an accurate and predictive computational framework for the description of complex aqueous solutions is an ongoing challenge for density functional theory based first-principles molecular dynamics (FPMD) simulations. In this context, important advances have been made in recent years, including the development of sophisticated exchange-correlation functionals. On the other hand, simulations based on simple generalized gradient approximation (GGA) functionals remain an active field, particularly in the study of complex aqueous solutions due to a good balance between the accuracy, computational expense, and the applicability to a wide range of systems. In such simulations we often perform them at elevated temperaturesmore » to artificially “correct” for GGA inaccuracies in the description of liquid water; however, a detailed understanding of how the choice of temperature affects the structure and dynamics of other components, such as solvated ions, is largely unknown. In order to address this question, we carried out a series of FPMD simulations at temperatures ranging from 300 to 460 K for liquid water and three representative aqueous solutions containing solvated Na +, K +, and Cl - ions. We show that simulations at 390–400 K with the Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional yield water structure and dynamics in good agreement with experiments at ambient conditions. Simultaneously, this computational setup provides ion solvation structures and ion effects on water dynamics consistent with experiments. These results suggest that an elevated temperature around 390–400 K with the PBE functional can be used for the description of structural and dynamical properties of liquid water and complex solutions with solvated ions at ambient conditions.« less

Structure and dynamics of aqueous solutions from PBE-based first-principles molecular dynamics simulations

DOE PAGES

Pham, Tuan Anh; Ogitsu, Tadashi; Lau, Edmond Y.; ...

2016-10-17

Establishing an accurate and predictive computational framework for the description of complex aqueous solutions is an ongoing challenge for density functional theory based first-principles molecular dynamics (FPMD) simulations. In this context, important advances have been made in recent years, including the development of sophisticated exchange-correlation functionals. On the other hand, simulations based on simple generalized gradient approximation (GGA) functionals remain an active field, particularly in the study of complex aqueous solutions due to a good balance between the accuracy, computational expense, and the applicability to a wide range of systems. In such simulations we often perform them at elevated temperaturesmore » to artificially “correct” for GGA inaccuracies in the description of liquid water; however, a detailed understanding of how the choice of temperature affects the structure and dynamics of other components, such as solvated ions, is largely unknown. In order to address this question, we carried out a series of FPMD simulations at temperatures ranging from 300 to 460 K for liquid water and three representative aqueous solutions containing solvated Na +, K +, and Cl - ions. We show that simulations at 390–400 K with the Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional yield water structure and dynamics in good agreement with experiments at ambient conditions. Simultaneously, this computational setup provides ion solvation structures and ion effects on water dynamics consistent with experiments. These results suggest that an elevated temperature around 390–400 K with the PBE functional can be used for the description of structural and dynamical properties of liquid water and complex solutions with solvated ions at ambient conditions.« less

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

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

NASA Astrophysics Data System (ADS)

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

2018-06-01

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

Ezrin tunes T-cell activation by controlling Dlg1 and microtubule positioning at the immunological synapse

PubMed Central

Lasserre, Rémi; Charrin, Stéphanie; Cuche, Céline; Danckaert, Anne; Thoulouze, Maria-Isabel; de Chaumont, Fabrice; Duong, Tarn; Perrault, Nathalie; Varin-Blank, Nadine; Olivo-Marin, Jean-Christophe; Etienne-Manneville, Sandrine; Arpin, Monique; Di Bartolo, Vincenzo; Alcover, Andrés

2010-01-01

T-cell receptor (TCR) signalling is triggered and tuned at immunological synapses by the generation of signalling complexes that associate into dynamic microclusters. Microcluster movement is necessary to tune TCR signalling, but the molecular mechanism involved remains poorly known. We show here that the membrane-microfilament linker ezrin has an important function in microcluster dynamics and in TCR signalling through its ability to set the microtubule network organization at the immunological synapse. Importantly, ezrin and microtubules are important to down-regulate signalling events leading to Erk1/2 activation. In addition, ezrin is required for appropriate NF-AT activation through p38 MAP kinase. Our data strongly support the notion that ezrin regulates immune synapse architecture and T-cell activation through its interaction with the scaffold protein Dlg1. These results uncover a crucial function for ezrin, Dlg1 and microtubules in the organization of the immune synapse and TCR signal down-regulation. Moreover, they underscore the importance of ezrin and Dlg1 in the regulation of NF-AT activation through p38. PMID:20551903

Abnormal early dynamic individual patterns of functional networks in low gamma band for depression recognition.

PubMed

Bi, Kun; Chattun, Mahammad Ridwan; Liu, Xiaoxue; Wang, Qiang; Tian, Shui; Zhang, Siqi; Lu, Qing; Yao, Zhijian

2018-06-13

The functional networks are associated with emotional processing in depression. The mapping of dynamic spatio-temporal brain networks is used to explore individual performance during early negative emotional processing. However, the dysfunctions of functional networks in low gamma band and their discriminative potentialities during early period of emotional face processing remain to be explored. Functional brain networks were constructed from the MEG recordings of 54 depressed patients and 54 controls in low gamma band (30-48 Hz). Dynamic connectivity regression (DCR) algorithm analyzed the individual change points of time series in response to emotional stimuli and constructed individualized spatio-temporal patterns. The nodal characteristics of patterns were calculated and fed into support vector machine (SVM). Performance of the classification algorithm in low gamma band was validated by dynamic topological characteristics of individual patterns in comparison to alpha and beta band. The best discrimination accuracy of individual spatio-temporal patterns was 91.01% in low gamma band. Individual temporal patterns had better results compared to group-averaged temporal patterns in all bands. The most important discriminative networks included affective network (AN) and fronto-parietal network (FPN) in low gamma band. The sample size is relatively small. High gamma band was not considered. The abnormal dynamic functional networks in low gamma band during early emotion processing enabled depression recognition. The individual information processing is crucial in the discovery of abnormal spatio-temporal patterns in depression during early negative emotional processing. Individual spatio-temporal patterns may reflect the real dynamic function of subjects while group-averaged data may neglect some individual information. Copyright © 2018. Published by Elsevier B.V.

Girsanov reweighting for path ensembles and Markov state models

NASA Astrophysics Data System (ADS)

Donati, L.; Hartmann, C.; Keller, B. G.

2017-06-01

The sensitivity of molecular dynamics on changes in the potential energy function plays an important role in understanding the dynamics and function of complex molecules. We present a method to obtain path ensemble averages of a perturbed dynamics from a set of paths generated by a reference dynamics. It is based on the concept of path probability measure and the Girsanov theorem, a result from stochastic analysis to estimate a change of measure of a path ensemble. Since Markov state models (MSMs) of the molecular dynamics can be formulated as a combined phase-space and path ensemble average, the method can be extended to reweight MSMs by combining it with a reweighting of the Boltzmann distribution. We demonstrate how to efficiently implement the Girsanov reweighting in a molecular dynamics simulation program by calculating parts of the reweighting factor "on the fly" during the simulation, and we benchmark the method on test systems ranging from a two-dimensional diffusion process and an artificial many-body system to alanine dipeptide and valine dipeptide in implicit and explicit water. The method can be used to study the sensitivity of molecular dynamics on external perturbations as well as to reweight trajectories generated by enhanced sampling schemes to the original dynamics.

Real-time observation of the conformational dynamics of mitochondrial Hsp70 by spFRET.

PubMed

Sikor, Martin; Mapa, Koyeli; von Voithenberg, Lena Voith; Mokranjac, Dejana; Lamb, Don C

2013-05-29

The numerous functions of the important class of molecular chaperones, heat shock proteins 70 (Hsp70), rely on cycles of intricate conformational changes driven by ATP-hydrolysis and regulated by cochaperones and substrates. Here, we used Förster resonance energy transfer to study the conformational dynamics of individual molecules of Ssc1, a mitochondrial Hsp70, in real time. The intrinsic dynamics of the substrate-binding domain of Ssc1 was observed to be uncoupled from the dynamic interactions between substrate- and nucleotide-binding domains. Analysis of the fluctuations in the interdomain separation revealed frequent transitions to a nucleotide-free state. The nucleotide-exchange factor Mge1 did not induce ADP release, as expected, but rather facilitated binding of ATP. These results indicate that the conformational cycle of Ssc1 is more elaborate than previously thought and provide insight into how the Hsp70s can perform a wide variety of functions.

Priming alters soil carbon dynamics during forest succession

NASA Astrophysics Data System (ADS)

Qiao, Na; Xu, Xingliang; Wang, Juan; Kuzyakov, Yakov

2017-04-01

The mechanisms underlying soil carbon (C) dynamics during forest succession remain challenged. We examined priming of soil organic matter (SOM) decomposition along a vegetation succession: grassland, young and old-growth forests. Soil C was primed much more strongly in young secondary forest than in grassland or old-growth forest. Priming resulted in large C losses (negative net C balance) in young-forest soil, whereas C stocks increased in grassland and old-growth forest. Microbial composition assessed by phospholipid fatty acids (PLFA) and utilization of easily available organics (13C-PLFA) indicate that fungi were responsible for priming in young-forest soils. Consequently, labile C inputs released by litter decomposition and root exudation determine microbial functional groups that decompose SOM during forest succession. These findings provide novel insights into connections between SOM dynamics and stabilization with microbial functioning during forest succession and show that priming is an important mechanism for contrasting soil C dynamics in young and old-growth forests.

Capturing the Interplay of Dynamics and Networks through Parameterizations of Laplacian Operators

DTIC Science & Technology

2016-08-24

important vertices and communities in the network. Specifically, for each dynamical process in this framework, we define a centrality measure that...vertices as a potential cluster (or community ) with respect to this process. We show that the subset-quality function generalizes the traditional conductance...compare the different perspectives they create on network structure. Subjects Network Science and Online Social Networks Keywords Network, Community

Protonation-state-Coupled Conformational Dynamics in Reaction Mechanisms of Channel and Pump Rhodopsins

DOE PAGES

Bondar, Ana-Nicoleta; Smith, Jeremy C.

2017-07-25

Channel and pump rhodopsins use energy from light absorbed by a covalently bound retinal chromophore to transport ions across membranes of microbial cells. Ion transfer steps, including proton transfer, can couple to changes in protein conformational dynamics and water positions. Although general principles of how microbial rhodopsins function are largely understood, key issues pertaining to reaction mechanisms remain unclear. Here, we compare the protonation-coupled dynamics of pump and channelrhodopsins, highlighting the roles that water dynamics, protein electrostatics and protein flexibility can have in ion transport mechanisms. We discuss observations supporting important functional roles of inter- and intra-helical carboxylate/hydroxyl hydrogen-bonding motifs.more » Specifically, we use the proton pump bacteriorhodopsin, the sodium pump KR2, channelrhodopsins and Anabaena sensory rhodopsin. We outline the usefulness of theoretic biophysics approaches to the study of retinal proteins, challenges in studying the hydrogen-bond dynamics of rhodopsin active sites, and implications for conformational coupling in membrane transporters.« less

Protonation-state-Coupled Conformational Dynamics in Reaction Mechanisms of Channel and Pump Rhodopsins

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

Bondar, Ana-Nicoleta; Smith, Jeremy C.

Channel and pump rhodopsins use energy from light absorbed by a covalently bound retinal chromophore to transport ions across membranes of microbial cells. Ion transfer steps, including proton transfer, can couple to changes in protein conformational dynamics and water positions. Although general principles of how microbial rhodopsins function are largely understood, key issues pertaining to reaction mechanisms remain unclear. Here, we compare the protonation-coupled dynamics of pump and channelrhodopsins, highlighting the roles that water dynamics, protein electrostatics and protein flexibility can have in ion transport mechanisms. We discuss observations supporting important functional roles of inter- and intra-helical carboxylate/hydroxyl hydrogen-bonding motifs.more » Specifically, we use the proton pump bacteriorhodopsin, the sodium pump KR2, channelrhodopsins and Anabaena sensory rhodopsin. We outline the usefulness of theoretic biophysics approaches to the study of retinal proteins, challenges in studying the hydrogen-bond dynamics of rhodopsin active sites, and implications for conformational coupling in membrane transporters.« less

Family dynamics and psychosocial functioning in children with SCI/D from Colombia, South America

PubMed Central

Nicolais, Christina J.; Perrin, Paul B.; Panyavin, Ivan; Nicholls, Elizabeth G.; Olivera Plaza, Silvia Leonor; Quintero, Lorena Medina; Arango-Lasprilla, Juan Carlos

2016-01-01

Objective The purpose of this study was to examine the connections between family dynamics and the psychosocial functioning of children with spinal cord injuries and disorders (SCI/D). Design Cross-sectional. Setting Participants were recruited from communities in Neiva, Colombia. Participants Thirty children with SCI/D and their primary caregiver participated. Children were between 8 and 17 years of age, and had sustained their injury at least six months prior to data collection. Interventions NA. Outcome measures Participating children completed measures assessing their own psychosocial functioning (Children's Depression Inventory, Revised Children's Manifest Anxiety Scale-2, Pediatric Quality of Life Inventory), and their primary caregiver completed measures of family dynamics (Family Adaptability and Cohesion Evaluation Scale- Fourth Edition, Family Communication Scale, Family Assessment Device- General Functioning, Family Satisfaction Scale, Relationship-Focused Coping Scale). Results A correlation matrix showed a number of significant bivariate correlations between child and family variables, and three multiple regressions showed that family satisfaction, empathy, and flexibility significantly explained 27% of the variance in child worry; family satisfaction and communication explained 18% of the variance in child social anxiety; and family cohesion and communication explained 23% of the variance in child emotional functioning. Conclusions These findings highlight the importance of rehabilitation professionals considering the association between family dynamics and the psychosocial functioning of children with SCI/D when working with this population. PMID:25582185

Eyes Open on Sleep and Wake: In Vivo to In Silico Neural Networks

PubMed Central

Vanvinckenroye, Amaury; Vandewalle, Gilles; Chellappa, Sarah L.

2016-01-01

Functional and effective connectivity of cortical areas are essential for normal brain function under different behavioral states. Appropriate cortical activity during sleep and wakefulness is ensured by the balanced activity of excitatory and inhibitory circuits. Ultimately, fast, millisecond cortical rhythmic oscillations shape cortical function in time and space. On a much longer time scale, brain function also depends on prior sleep-wake history and circadian processes. However, much remains to be established on how the brain operates at the neuronal level in humans during sleep and wakefulness. A key limitation of human neuroscience is the difficulty in isolating neuronal excitation/inhibition drive in vivo. Therefore, computational models are noninvasive approaches of choice to indirectly access hidden neuronal states. In this review, we present a physiologically driven in silico approach, Dynamic Causal Modelling (DCM), as a means to comprehend brain function under different experimental paradigms. Importantly, DCM has allowed for the understanding of how brain dynamics underscore brain plasticity, cognition, and different states of consciousness. In a broader perspective, noninvasive computational approaches, such as DCM, may help to puzzle out the spatial and temporal dynamics of human brain function at different behavioural states. PMID:26885400

Neuronal avalanches and coherence potentials

NASA Astrophysics Data System (ADS)

Plenz, D.

2012-05-01

The mammalian cortex consists of a vast network of weakly interacting excitable cells called neurons. Neurons must synchronize their activities in order to trigger activity in neighboring neurons. Moreover, interactions must be carefully regulated to remain weak (but not too weak) such that cascades of active neuronal groups avoid explosive growth yet allow for activity propagation over long-distances. Such a balance is robustly realized for neuronal avalanches, which are defined as cortical activity cascades that follow precise power laws. In experiments, scale-invariant neuronal avalanche dynamics have been observed during spontaneous cortical activity in isolated preparations in vitro as well as in the ongoing cortical activity of awake animals and in humans. Theory, models, and experiments suggest that neuronal avalanches are the signature of brain function near criticality at which the cortex optimally responds to inputs and maximizes its information capacity. Importantly, avalanche dynamics allow for the emergence of a subset of avalanches, the coherence potentials. They emerge when the synchronization of a local neuronal group exceeds a local threshold, at which the system spawns replicas of the local group activity at distant network sites. The functional importance of coherence potentials will be discussed in the context of propagating structures, such as gliders in balanced cellular automata. Gliders constitute local population dynamics that replicate in space after a finite number of generations and are thought to provide cellular automata with universal computation. Avalanches and coherence potentials are proposed to constitute a modern framework of cortical synchronization dynamics that underlies brain function.

Neutral Theory and Scale-Free Neural Dynamics

NASA Astrophysics Data System (ADS)

Martinello, Matteo; Hidalgo, Jorge; Maritan, Amos; di Santo, Serena; Plenz, Dietmar; Muñoz, Miguel A.

2017-10-01

Neural tissues have been consistently observed to be spontaneously active and to generate highly variable (scale-free distributed) outbursts of activity in vivo and in vitro. Understanding whether these heterogeneous patterns of activity stem from the underlying neural dynamics operating at the edge of a phase transition is a fascinating possibility, as criticality has been argued to entail many possible important functional advantages in biological computing systems. Here, we employ a well-accepted model for neural dynamics to elucidate an alternative scenario in which diverse neuronal avalanches, obeying scaling, can coexist simultaneously, even if the network operates in a regime far from the edge of any phase transition. We show that perturbations to the system state unfold dynamically according to a "neutral drift" (i.e., guided only by stochasticity) with respect to the background of endogenous spontaneous activity, and that such a neutral dynamics—akin to neutral theories of population genetics and of biogeography—implies marginal propagation of perturbations and scale-free distributed causal avalanches. We argue that causal information, not easily accessible to experiments, is essential to elucidate the nature and statistics of neural avalanches, and that neutral dynamics is likely to play an important role in the cortex functioning. We discuss the implications of these findings to design new empirical approaches to shed further light on how the brain processes and stores information.

EB-Family Proteins: Functions and Microtubule Interaction Mechanisms.

PubMed

Mustyatsa, V V; Boyakhchyan, A V; Ataullakhanov, F I; Gudimchuk, N B

2017-07-01

Microtubules are polymers of tubulin protein, one of the key components of cytoskeleton. They are polar filaments whose plus-ends usually oriented toward the cell periphery are more dynamic than their minus-ends, which face the center of the cell. In cells, microtubules are organized into a network that is being constantly rebuilt and renovated due to stochastic switching of its individual filaments from growth to shrinkage and back. Because of these dynamics and their mechanical properties, microtubules take part in various essential processes, from intracellular transport to search and capture of chromosomes during mitosis. Microtubule dynamics are regulated by many proteins that are located on the plus-ends of these filaments. One of the most important and abundant groups of plus-end-interacting proteins are EB-family proteins, which autonomously recognize structures of the microtubule growing plus-ends, modulate their dynamics, and recruit multiple partner proteins with diverse functions onto the microtubule plus-ends. In this review, we summarize the published data about the properties and functions of EB-proteins, focusing on analysis of their mechanism of interaction with the microtubule growing ends.

Modulation of hemoglobin dynamics by an allosteric effector

DOE PAGES

Lal, Jyotsana; Maccarini, Marco; Fouquet, Peter; ...

2016-12-15

Hemoglobin (Hb) is an extensively studied paradigm of proteins that alter their function in response to allosteric effectors. Models of its action have been used as prototypes for structure-function relationships in many proteins, and models for the molecular basis of its function have been deeply studied and extensively argued. Recent reports suggest that dynamics may play an important role in its function. Relatively little is known about the slow, correlated motions of hemoglobin subunits in various structural states because experimental and computational strategies for their characterization are challenging. Allosteric effectors such as inositol hexaphosphate (IHP) bind to both deoxy-Hb andmore » HbCO, albeit at different sites, leading to a lowered oxygen affinity. The manner in which these effectors impact oxygen binding is unclear and may involve changes in structure, dynamics or both. Here we use neutron spin echo (NSE) measurements accompanied by wideangle x-ray scattering (WAXS) to show that binding of IHP to HbCO results in an increase in the rate of coordinated motions of Hb subunits relative to one another with little if any change in large scale structure. This increase of large-scale dynamics seems to be coupled with a decrease in the average magnitude of higher frequency modes of individual residues. Furthermore, these observations indicate that enhanced dynamic motions contribute to the functional changes induced by IHP and suggest that they may be responsible for the lowered oxygen affinity triggered by these effectors.« less

In vitro models and systems for evaluating the dynamics of drug delivery to the healthy and diseased brain.

PubMed

Modarres, Hassan Pezeshgi; Janmaleki, Mohsen; Novin, Mana; Saliba, John; El-Hajj, Fatima; RezayatiCharan, Mahdi; Seyfoori, Amir; Sadabadi, Hamid; Vandal, Milène; Nguyen, Minh Dang; Hasan, Anwarul; Sanati-Nezhad, Amir

2018-03-10

The blood-brain barrier (BBB) plays a crucial role in maintaining brain homeostasis and transport of drugs to the brain. The conventional animal and Transwell BBB models along with emerging microfluidic-based BBB-on-chip systems have provided fundamental functionalities of the BBB and facilitated the testing of drug delivery to the brain tissue. However, developing biomimetic and predictive BBB models capable of reasonably mimicking essential characteristics of the BBB functions is still a challenge. In addition, detailed analysis of the dynamics of drug delivery to the healthy or diseased brain requires not only biomimetic BBB tissue models but also new systems capable of monitoring the BBB microenvironment and dynamics of barrier function and delivery mechanisms. This review provides a comprehensive overview of recent advances in microengineering of BBB models with different functional complexity and mimicking capability of healthy and diseased states. It also discusses new technologies that can make the next generation of biomimetic human BBBs containing integrated biosensors for real-time monitoring the tissue microenvironment and barrier function and correlating it with the dynamics of drug delivery. Such integrated system addresses important brain drug delivery questions related to the treatment of brain diseases. We further discuss how the combination of in vitro BBB systems, computational models and nanotechnology supports for characterization of the dynamics of drug delivery to the brain. Copyright © 2018 Elsevier B.V. All rights reserved.

Quantum and classical dynamics of water dissociation on Ni(111): A test of the site-averaging model in dissociative chemisorption of polyatomic molecules

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

Jiang, Bin; Department of Chemical Physics, University of Science and Technology of China, Hefei 230026; Guo, Hua, E-mail: hguo@unm.edu

Recently, we reported the first highly accurate nine-dimensional global potential energy surface (PES) for water interacting with a rigid Ni(111) surface, built on a large number of density functional theory points [B. Jiang and H. Guo, Phys. Rev. Lett. 114, 166101 (2015)]. Here, we investigate site-specific reaction probabilities on this PES using a quasi-seven-dimensional quantum dynamical model. It is shown that the site-specific reactivity is largely controlled by the topography of the PES instead of the barrier height alone, underscoring the importance of multidimensional dynamics. In addition, the full-dimensional dissociation probability is estimated by averaging fixed-site reaction probabilities with appropriatemore » weights. To validate this model and gain insights into the dynamics, additional quasi-classical trajectory calculations in both full and reduced dimensions have also been performed and important dynamical factors such as the steering effect are discussed.« less

The Role of Linkers in the Excited-State Dynamic Planarization Processes of Macrocyclic Oligothiophene 12-Mers.

PubMed

Kim, Woojae; Sung, Jooyoung; Park, Kyu Hyung; Shimizu, Hideyuki; Imamura, Mika; Han, Minwoo; Sim, Eunji; Iyoda, Masahiko; Kim, Dongho

2015-11-05

Linkers adjoining chromophores play an important role in modulating the structure of conjugated systems, which is bound up with their photophysical properties. However, to date, the focus of works dealing with linker effects was limited only to linear π-conjugated materials, and there have been no detailed studies on cyclic counterparts. Herein we report the linker effects on the dynamic planarization processes of π-conjugated macrocyclic oligothiophene 12-mers, where the different ratio between ethynylene and vinylene linkers was chosen to control the backbone rigidity. By analyzing transient fluorescence spectra, we demonstrate that the connecting linkers play a crucial role in the excited-state dynamics of cyclic conjugated systems. Faster dynamic planarization, longer exciton delocalization length, and higher degree of planarity were observed in vinylene inserted cyclic oligothiophenes. Molecular dynamics simulations and density functional theory calculations also stress the importance of the role of linkers in modulating the structure of cyclic oligothiophenes.

Distinct functional outputs of PTEN signalling are controlled by dynamic association with β-arrestins

PubMed Central

Lima-Fernandes, Evelyne; Enslen, Hervé; Camand, Emeline; Kotelevets, Larissa; Boularan, Cédric; Achour, Lamia; Benmerah, Alexandre; Gibson, Lucien C D; Baillie, George S; Pitcher, Julie A; Chastre, Eric; Etienne-Manneville, Sandrine; Marullo, Stefano; Scott, Mark G H

2011-01-01

The tumour suppressor PTEN (phosphatase and tensin deleted on chromosome 10) regulates major cellular functions via lipid phosphatase-dependent and -independent mechanisms. Despite its fundamental pathophysiological importance, how PTEN's cellular activity is regulated has only been partially elucidated. We report that the scaffolding proteins β-arrestins (β-arrs) are important regulators of PTEN. Downstream of receptor-activated RhoA/ROCK signalling, β-arrs activate the lipid phosphatase activity of PTEN to negatively regulate Akt and cell proliferation. In contrast, following wound-induced RhoA activation, β-arrs inhibit the lipid phosphatase-independent anti-migratory effects of PTEN. β-arrs can thus differentially control distinct functional outputs of PTEN important for cell proliferation and migration. PMID:21642958

Effects of Temporal Integration on the Shape of Visual Backward Masking Functions

ERIC Educational Resources Information Center

Francis, Gregory; Cho, Yang Seok

2008-01-01

Many studies of cognition and perception use a visual mask to explore the dynamics of information processing of a target. Especially important in these applications is the time between the target and mask stimuli. A plot of some measure of target visibility against stimulus onset asynchrony is called a masking function, which can sometimes be…

Teaching Cardiac Autonomic Function Dynamics Employing the Valsalva (Valsalva-Weber) Maneuver

ERIC Educational Resources Information Center

Junqueira, Luiz Fernando, Jr.

2008-01-01

In this report, a brief history of the Valsalva (Valsalva-Weber) maneuver is outlined, followed by an explanation on the use of this approach for the evaluation of cardiac autonomic function based on underlying heart rate changes. The most important methodological and interpretative aspects of the Valsalva-Weber maneuver are critically updated,…

Gene networks, occlusal clocks, and functional patches: new understanding of pattern and process in the evolution of the dentition.

PubMed

Polly, P David

2015-05-01

Our understanding of the evolution of the dentition has been transformed by advances in the developmental biology, genetics, and functional morphology of teeth, as well as the methods available for studying tooth form and function. The hierarchical complexity of dental developmental genetics combined with dynamic effects of cells and tissues during development allow for substantial, rapid, and potentially non-linear evolutionary changes. Studies of selection on tooth function in the wild and evolutionary functional comparisons both suggest that tooth function and adaptation to diets are the most important factors guiding the evolution of teeth, yet selection against random changes that produce malocclusions (selectional drift) may be an equally important factor in groups with tribosphenic dentitions. These advances are critically reviewed here.

Dynamics of biological systems: role of systems biology in medical research.

PubMed

Assmus, Heike E; Herwig, Ralf; Cho, Kwang-Hyun; Wolkenhauer, Olaf

2006-11-01

Cellular systems are networks of interacting components that change with time in response to external and internal events. Studying the dynamic behavior of these networks is the basis for an understanding of cellular functions and disease mechanisms. Quantitative time-series data leading to meaningful models can improve our knowledge of human physiology in health and disease, and aid the search for earlier diagnoses, better therapies and a healthier life. The advent of systems biology is about to take the leap into clinical research and medical applications. This review emphasizes the importance of a dynamic view and understanding of cell function. We discuss the potential for computer-aided mathematical modeling of biological systems in medical research with examples from some of the major therapeutic areas: cancer, cardiovascular, diabetic and neurodegenerative medicine.

Event-induced theta responses as a window on the dynamics of memory.

PubMed

Bastiaansen, Marcel; Hagoort, Peter

2003-01-01

An important, but often ignored distinction in the analysis of EEG signals is that between evoked activity and induced activity. Whereas evoked activity reflects the summation of transient post-synaptic potentials triggered by an event, induced activity, which is mainly oscillatory in nature, is thought to reflect changes in parameters controlling dynamic interactions within and between brain structures. We hypothesize that induced activity may yield information about the dynamics of cell assembly formation, activation and subsequent uncoupling, which may play a prominent role in different types of memory operations. We then describe a number of analysis tools that can be used to study the reactivity of induced rhythmic activity, both in terms of amplitude changes and of phase variability. We briefly discuss how alpha, gamma and theta rhythms are thought to be generated, paying special attention to the hypothesis that the theta rhythm reflects dynamic interactions between the hippocampal system and the neocortex. This hypothesis would imply that studying the reactivity of scalp-recorded theta may provide a window on the contribution of the hippocampus to memory functions. We review studies investigating the reactivity of scalp-recorded theta in paradigms engaging episodic memory, spatial memory and working memory. In addition, we review studies that relate theta reactivity to processes at the interface of memory and language. Despite many unknowns, the experimental evidence largely supports the hypothesis that theta activity plays a functional role in cell assembly formation, a process which may constitute the neural basis of memory formation and retrieval. The available data provide only highly indirect support for the hypothesis that scalp-recorded theta yields information about hippocampal functioning. It is concluded that studying induced rhythmic activity holds promise as an additional important way to study brain function.

A Molecular Approach to Mitophagy and Mitochondrial Dynamics

PubMed Central

Yoo, Seung-Min; Jung, Yong-Keun

2018-01-01

Mitochondrial quality control systems are essential for the maintenance of functional mitochondria. At the organelle level, they include mitochondrial biogenesis, fusion and fission, to compensate for mitochondrial function, and mitophagy, for degrading damaged mitochondria. Specifically, in mitophagy, the target mitochondria are recognized by the autophagosomes and delivered to the lysosome for degradation. In this review, we describe the mechanisms of mitophagy and the factors that play an important role in this process. In particular, we focus on the roles of mitophagy adapters and receptors in the recognition of damaged mitochondria by autophagosomes. In addition, we also address a functional association of mitophagy with mitochondrial dynamics through the interaction of mitophagy adaptor and receptor proteins with mitochondrial fusion and fission proteins. PMID:29370689

Dynamic recruitment of resting state sub-networks

PubMed Central

O'Neill, George C.; Bauer, Markus; Woolrich, Mark W.; Morris, Peter G.; Barnes, Gareth R.; Brookes, Matthew J.

2015-01-01

Resting state networks (RSNs) are of fundamental importance in human systems neuroscience with evidence suggesting that they are integral to healthy brain function and perturbed in pathology. Despite rapid progress in this area, the temporal dynamics governing the functional connectivities that underlie RSN structure remain poorly understood. Here, we present a framework to help further our understanding of RSN dynamics. We describe a methodology which exploits the direct nature and high temporal resolution of magnetoencephalography (MEG). This technique, which builds on previous work, extends from solving fundamental confounds in MEG (source leakage) to multivariate modelling of transient connectivity. The resulting processing pipeline facilitates direct (electrophysiological) measurement of dynamic functional networks. Our results show that, when functional connectivity is assessed in small time windows, the canonical sensorimotor network can be decomposed into a number of transiently synchronising sub-networks, recruitment of which depends on current mental state. These rapidly changing sub-networks are spatially focal with, for example, bilateral primary sensory and motor areas resolved into two separate sub-networks. The likely interpretation is that the larger canonical sensorimotor network most often seen in neuroimaging studies reflects only a temporal aggregate of these transient sub-networks. Our approach opens new frontiers to study RSN dynamics, showing that MEG is capable of revealing the spatial, temporal and spectral signature of the human connectome in health and disease. PMID:25899137

Short-range density functional correlation within the restricted active space CI method

NASA Astrophysics Data System (ADS)

Casanova, David

2018-03-01

In the present work, I introduce a hybrid wave function-density functional theory electronic structure method based on the range separation of the electron-electron Coulomb operator in order to recover dynamic electron correlations missed in the restricted active space configuration interaction (RASCI) methodology. The working equations and the computational algorithm for the implementation of the new approach, i.e., RAS-srDFT, are presented, and the method is tested in the calculation of excitation energies of organic molecules. The good performance of the RASCI wave function in combination with different short-range exchange-correlation functionals in the computation of relative energies represents a quantitative improvement with respect to the RASCI results and paves the path for the development of RAS-srDFT as a promising scheme in the computation of the ground and excited states where nondynamic and dynamic electron correlations are important.

Microevolutionary dynamics of a macroevolutionary key innovation in a Lepidopteran herbivore

PubMed Central

2010-01-01

Background A molecular population genetics understanding is central to the study of ecological and evolutionary functional genomics. Population genetics identifies genetic variation and its distribution within and among populations, it reveals the demographic history of the populations studied, and can provide indirect insights into historical selection dynamics. Here we use this approach to examine the demographic and selective dynamics acting of a candidate gene involved in plant-insect interactions. Previous work documents the macroevolutionary and historical ecological importance of the nitrile-specifier protein (Nsp), which facilitated the host shift of Pieridae butterflies onto Brassicales host plants ~80 Myr ago. Results Here we assess the microevolutionary dynamics of the Nsp gene by studying the within and among-population variation at Nsp and reference genes in the butterfly Pieris rapae (Small Cabbage White). Nsp exhibits unexpectedly high amounts of amino acid polymorphism, unequally distributed across the gene. The vast majority of genetic variation exists within populations, with little to no genetic differentiation among four populations on two continents. A comparison of synonymous and nonsynonymous substitutions in 70 randomly chosen genes among P. rapae and its close relative Pieris brassicae (Large Cabbage White) finds Nsp to have a significantly relaxed functional constraint compared to housekeeping genes. We find strong evidence for a recent population expansion and no role for strong purifying or directional selection upon the Nsp gene. Conclusions The microevolutionary dynamics of the Nsp gene in P. rapae are dominated by recent population expansion and variation in functional constraint across the repeated domains of the Nsp gene. While the high amounts of amino acid diversity suggest there may be significant functional differences among allelic variants segregating within populations, indirect tests of selection could not conclusively identify a signature of historical selection. The importance of using this information for planning future studies of potential performance and fitness consequences of the observed variation is discussed. PMID:20181249

Dynamic culture yields engineered myocardium with near-adult functional output

PubMed Central

Jackman, Christopher P.; Carlson, Aaron L.; Bursac, Nenad

2016-01-01

Engineered cardiac tissues hold promise for cell therapy and drug development, but exhibit inadequate function and maturity. In this study, we sought to significantly improve the function and maturation of rat and human engineered cardiac tissues. We developed dynamic, free-floating culture conditions for engineering “cardiobundles”, 3-dimensional cylindrical tissues made from neonatal rat cardiomyocytes or human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) embedded in fibrin-based hydrogel. Compared to static culture, 2-week dynamic culture of neonatal rat cardiobundles significantly increased expression of sarcomeric proteins, cardiomyocyte size (~2.1-fold), contractile force (~3.5-fold), and conduction velocity of action potentials (~1.4-fold). The average contractile force per cross-sectional area (59.7 mN/mm2) and conduction velocity (52.5 cm/sec) matched or approached those of adult rat myocardium, respectively. The inferior function of statically cultured cardiobundles was rescued by transfer to dynamic conditions, which was accompanied by an increase in mTORC1 activity and decline in AMPK phosphorylation and was blocked by rapamycin. Furthermore, dynamic culture effects did not stimulate ERK1/2 pathway and were insensitive to blockers of mechanosensitive channels, suggesting increased nutrient availability rather than mechanical stimulation as the upstream activator of mTORC1. Direct comparison with phenylephrine treatment confirmed that dynamic culture promoted physiological cardiomyocyte growth rather than pathological hypertrophy. Optimized dynamic culture conditions also augmented function of human cardiobundles made reproducibly from cardiomyocytes derived from multiple hPSC lines, resulting in significantly increased contraction force (~2.5-fold) and conduction velocity (~1.4-fold). The average specific force of 23.2 mN/mm2 and conduction velocity of 25.8 cm/sec approached the functional metrics of adult human myocardium. In conclusion, we have developed a versatile methodology for engineering cardiac tissues with a near-adult functional output without the need for exogenous electrical or mechanical stimulation, and have identified mTOR signaling as an important mechanism for advancing tissue maturation and function in vitro. PMID:27723557

Dynamic culture yields engineered myocardium with near-adult functional output.

PubMed

Jackman, Christopher P; Carlson, Aaron L; Bursac, Nenad

2016-12-01

Engineered cardiac tissues hold promise for cell therapy and drug development, but exhibit inadequate function and maturity. In this study, we sought to significantly improve the function and maturation of rat and human engineered cardiac tissues. We developed dynamic, free-floating culture conditions for engineering "cardiobundles", 3-dimensional cylindrical tissues made from neonatal rat cardiomyocytes or human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) embedded in fibrin-based hydrogel. Compared to static culture, 2-week dynamic culture of neonatal rat cardiobundles significantly increased expression of sarcomeric proteins, cardiomyocyte size (∼2.1-fold), contractile force (∼3.5-fold), and conduction velocity of action potentials (∼1.4-fold). The average contractile force per cross-sectional area (59.7 mN/mm 2 ) and conduction velocity (52.5 cm/s) matched or approached those of adult rat myocardium, respectively. The inferior function of statically cultured cardiobundles was rescued by transfer to dynamic conditions, which was accompanied by an increase in mTORC1 activity and decline in AMPK phosphorylation and was blocked by rapamycin. Furthermore, dynamic culture effects did not stimulate ERK1/2 pathway and were insensitive to blockers of mechanosensitive channels, suggesting increased nutrient availability rather than mechanical stimulation as the upstream activator of mTORC1. Direct comparison with phenylephrine treatment confirmed that dynamic culture promoted physiological cardiomyocyte growth rather than pathological hypertrophy. Optimized dynamic culture conditions also augmented function of human cardiobundles made reproducibly from cardiomyocytes derived from multiple hPSC lines, resulting in significantly increased contraction force (∼2.5-fold) and conduction velocity (∼1.4-fold). The average specific force of 23.2 mN/mm 2 and conduction velocity of 25.8 cm/s approached the functional metrics of adult human myocardium. In conclusion, we have developed a versatile methodology for engineering cardiac tissues with a near-adult functional output without the need for exogenous electrical or mechanical stimulation, and have identified mTOR signaling as an important mechanism for advancing tissue maturation and function in vitro. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of elevated atmospheric Co2 and tropospheric O3 on nutrient dynamics: decomposition of leaf litter in trembling aspen and paper birch communities. Plant Soil. 299:65–82.

Treesearch

Lingli Liu; John S. King; Christian P. Giardina

2007-01-01

Atmospheric changes could strongly influence how terrestrial ecosystems function by altering nutrient cycling. We examined how the dynamics of nutrient release from leaf litter responded to two important atmospheric changes: rising atmospheric Co2 and tropospheric O3. We evaluated the independent and combined effects of...

A concentrated parameter model for the human cardiovascular system including heart valve dynamics and atrioventricular interaction.

PubMed

Korakianitis, Theodosios; Shi, Yubing

2006-09-01

Numerical modeling of the human cardiovascular system has always been an active research direction since the 19th century. In the past, various simulation models of different complexities were proposed for different research purposes. In this paper, an improved numerical model to study the dynamic function of the human circulation system is proposed. In the development of the mathematical model, the heart chambers are described with a variable elastance model. The systemic and pulmonary loops are described based on the resistance-compliance-inertia concept by considering local effects of flow friction, elasticity of blood vessels and inertia of blood in different segments of the blood vessels. As an advancement from previous models, heart valve dynamics and atrioventricular interaction, including atrial contraction and motion of the annulus fibrosus, are specifically modeled. With these improvements the developed model can predict several important features that were missing in previous numerical models, including regurgitant flow on heart valve closure, the value of E/A velocity ratio in mitral flow, the motion of the annulus fibrosus (called the KG diaphragm pumping action), etc. These features have important clinical meaning and their changes are often related to cardiovascular diseases. Successful simulation of these features enhances the accuracy of simulations of cardiovascular dynamics, and helps in clinical studies of cardiac function.

Dynamic control and information processing in chemical reaction systems by tuning self-organization behavior

NASA Astrophysics Data System (ADS)

Lebiedz, Dirk; Brandt-Pollmann, Ulrich

2004-09-01

Specific external control of chemical reaction systems and both dynamic control and signal processing as central functions in biochemical reaction systems are important issues of modern nonlinear science. For example nonlinear input-output behavior and its regulation are crucial for the maintainance of the life process that requires extensive communication between cells and their environment. An important question is how the dynamical behavior of biochemical systems is controlled and how they process information transmitted by incoming signals. But also from a general point of view external forcing of complex chemical reaction processes is important in many application areas ranging from chemical engineering to biomedicine. In order to study such control issues numerically, here, we choose a well characterized chemical system, the CO oxidation on Pt(110), which is interesting per se as an externally forced chemical oscillator model. We show numerically that tuning of temporal self-organization by input signals in this simple nonlinear chemical reaction exhibiting oscillatory behavior can in principle be exploited for both specific external control of dynamical system behavior and processing of complex information.

Hydrogen exchange differences between chemoreceptor signaling complexes localize to functionally important subdomains.

PubMed

Koshy, Seena S; Li, Xuni; Eyles, Stephen J; Weis, Robert M; Thompson, Lynmarie K

2014-12-16

The goal of understanding mechanisms of transmembrane signaling, one of many key life processes mediated by membrane proteins, has motivated numerous studies of bacterial chemotaxis receptors. Ligand binding to the receptor causes a piston motion of an α helix in the periplasmic and transmembrane domains, but it is unclear how the signal is then propagated through the cytoplasmic domain to control the activity of the associated kinase CheA. Recent proposals suggest that signaling in the cytoplasmic domain involves opposing changes in dynamics in different subdomains. However, it has been difficult to measure dynamics within the functional system, consisting of extended arrays of receptor complexes with two other proteins, CheA and CheW. We have combined hydrogen exchange mass spectrometry with vesicle template assembly of functional complexes of the receptor cytoplasmic domain to reveal that there are significant signaling-associated changes in exchange, and these changes localize to key regions of the receptor involved in the excitation and adaptation responses. The methylation subdomain exhibits complex changes that include slower hydrogen exchange in complexes in a kinase-activating state, which may be partially consistent with proposals that this subdomain is stabilized in this state. The signaling subdomain exhibits significant protection from hydrogen exchange in complexes in a kinase-activating state, suggesting a tighter and/or larger interaction interface with CheA and CheW in this state. These first measurements of the stability of protein subdomains within functional signaling complexes demonstrate the promise of this approach for measuring functionally important protein dynamics within the various physiologically relevant states of multiprotein complexes.

Hydrogen Exchange Differences between Chemoreceptor Signaling Complexes Localize to Functionally Important Subdomains

PubMed Central

2015-01-01

The goal of understanding mechanisms of transmembrane signaling, one of many key life processes mediated by membrane proteins, has motivated numerous studies of bacterial chemotaxis receptors. Ligand binding to the receptor causes a piston motion of an α helix in the periplasmic and transmembrane domains, but it is unclear how the signal is then propagated through the cytoplasmic domain to control the activity of the associated kinase CheA. Recent proposals suggest that signaling in the cytoplasmic domain involves opposing changes in dynamics in different subdomains. However, it has been difficult to measure dynamics within the functional system, consisting of extended arrays of receptor complexes with two other proteins, CheA and CheW. We have combined hydrogen exchange mass spectrometry with vesicle template assembly of functional complexes of the receptor cytoplasmic domain to reveal that there are significant signaling-associated changes in exchange, and these changes localize to key regions of the receptor involved in the excitation and adaptation responses. The methylation subdomain exhibits complex changes that include slower hydrogen exchange in complexes in a kinase-activating state, which may be partially consistent with proposals that this subdomain is stabilized in this state. The signaling subdomain exhibits significant protection from hydrogen exchange in complexes in a kinase-activating state, suggesting a tighter and/or larger interaction interface with CheA and CheW in this state. These first measurements of the stability of protein subdomains within functional signaling complexes demonstrate the promise of this approach for measuring functionally important protein dynamics within the various physiologically relevant states of multiprotein complexes. PMID:25420045

Exploring the Dynamics of Transit Times and Subsurface Mixing in a Small Agricultural Catchment

NASA Astrophysics Data System (ADS)

Yang, Jie; Heidbüchel, Ingo; Musolff, Andreas; Reinstorf, Frido; Fleckenstein, Jan H.

2018-03-01

The analysis of transit/residence time distributions (TTDs and RTDs) provides important insights into the dynamics of stream-water ages and subsurface mixing. These insights have significant implications for water quality. For a small agricultural catchment in central Germany, we use a 3D fully coupled surface-subsurface hydrological model to simulate water flow and perform particle tracking to determine flow paths and transit times. The TTDs of discharge, RTDs of storage and fractional StorAge Selection (fSAS) functions are computed and analyzed on daily basis for a period of 10 years. Results show strong seasonal fluctuations of the median transit time of discharge and the median residence time, with the former being strongly related to the catchment wetness. Computed fSAS functions suggest systematic shifts of the discharge selection preference over four main periods: In the wet period, the youngest water in storage is preferentially selected, and this preference shifts gradually toward older ages of stored water when the catchment transitions into the drying, dry and wetting periods. These changes are driven by distinct shifts in the dominance of deeper flow paths and fast shallow flow paths. Changes in the shape of the fSAS functions can be captured by changes in the two parameters of the approximating Beta distributions, allowing the generation of continuous fSAS functions representing the general catchment behavior. These results improve our understanding of the seasonal dynamics of TTDs and fSAS functions for a complex real-world catchment and are important for interpreting solute export to the stream in a spatially implicit manner.

From Vesicles to Protocells: The Roles of Amphiphilic Molecules

PubMed Central

Sakuma, Yuka; Imai, Masayuki

2015-01-01

It is very challenging to construct protocells from molecular assemblies. An important step in this challenge is the achievement of vesicle dynamics that are relevant to cellular functions, such as membrane trafficking and self-reproduction, using amphiphilic molecules. Soft matter physics will play an important role in the development of vesicles that have these functions. Here, we show that simple binary phospholipid vesicles have the potential to reproduce the relevant functions of adhesion, pore formation and self-reproduction of vesicles, by coupling the lipid geometries (spontaneous curvatures) and the phase separation. This achievement will elucidate the pathway from molecular assembly to cellular life. PMID:25738256

Temporal and spectral characteristics of dynamic functional connectivity between resting-state networks reveal information beyond static connectivity

PubMed Central

Yeh, Hsiang J.; Guindani, Michele; Vannucci, Marina; Haneef, Zulfi; Stern, John M.

2018-01-01

Estimation of functional connectivity (FC) has become an increasingly powerful tool for investigating healthy and abnormal brain function. Static connectivity, in particular, has played a large part in guiding conclusions from the majority of resting-state functional MRI studies. However, accumulating evidence points to the presence of temporal fluctuations in FC, leading to increasing interest in estimating FC as a dynamic quantity. One central issue that has arisen in this new view of connectivity is the dramatic increase in complexity caused by dynamic functional connectivity (dFC) estimation. To computationally handle this increased complexity, a limited set of dFC properties, primarily the mean and variance, have generally been considered. Additionally, it remains unclear how to integrate the increased information from dFC into pattern recognition techniques for subject-level prediction. In this study, we propose an approach to address these two issues based on a large number of previously unexplored temporal and spectral features of dynamic functional connectivity. A Generalized Autoregressive Conditional Heteroskedasticity (GARCH) model is used to estimate time-varying patterns of functional connectivity between resting-state networks. Time-frequency analysis is then performed on dFC estimates, and a large number of previously unexplored temporal and spectral features drawn from signal processing literature are extracted for dFC estimates. We apply the investigated features to two neurologic populations of interest, healthy controls and patients with temporal lobe epilepsy, and show that the proposed approach leads to substantial increases in predictive performance compared to both traditional estimates of static connectivity as well as current approaches to dFC. Variable importance is assessed and shows that there are several quantities that can be extracted from dFC signal which are more informative than the traditional mean or variance of dFC. This work illuminates many previously unexplored facets of the dynamic properties of functional connectivity between resting-state networks, and provides a platform for dynamic functional connectivity analysis that facilitates its usage as an investigative measure for healthy as well as abnormal brain function. PMID:29320526

Detecting subnetwork-level dynamic correlations.

PubMed

Yan, Yan; Qiu, Shangzhao; Jin, Zhuxuan; Gong, Sihong; Bai, Yun; Lu, Jianwei; Yu, Tianwei

2017-01-15

The biological regulatory system is highly dynamic. The correlations between many functionally related genes change over different biological conditions. Finding dynamic relations on the existing biological network may reveal important regulatory mechanisms. Currently no method is available to detect subnetwork-level dynamic correlations systematically on the genome-scale network. Two major issues hampered the development. The first is gene expression profiling data usually do not contain time course measurements to facilitate the analysis of dynamic relations, which can be partially addressed by using certain genes as indicators of biological conditions. Secondly, it is unclear how to effectively delineate subnetworks, and define dynamic relations between them. Here we propose a new method named LANDD (Liquid Association for Network Dynamics Detection) to find subnetworks that show substantial dynamic correlations, as defined by subnetwork A is concentrated with Liquid Association scouting genes for subnetwork B. The method produces easily interpretable results because of its focus on subnetworks that tend to comprise functionally related genes. Also, the collective behaviour of genes in a subnetwork is a much more reliable indicator of underlying biological conditions compared to using single genes as indicators. We conducted extensive simulations to validate the method's ability to detect subnetwork-level dynamic correlations. Using a real gene expression dataset and the human protein-protein interaction network, we demonstrate the method links subnetworks of distinct biological processes, with both confirmed relations and plausible new functional implications. We also found signal transduction pathways tend to show extensive dynamic relations with other functional groups. The R package is available at https://cran.r-project.org/web/packages/LANDD CONTACTS: yunba@pcom.edu, jwlu33@hotmail.com or tianwei.yu@emory.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Angle-dependent strong-field molecular ionization rates with tuned range-separated time-dependent density functional theory.

PubMed

Sissay, Adonay; Abanador, Paul; Mauger, François; Gaarde, Mette; Schafer, Kenneth J; Lopata, Kenneth

2016-09-07

Strong-field ionization and the resulting electronic dynamics are important for a range of processes such as high harmonic generation, photodamage, charge resonance enhanced ionization, and ionization-triggered charge migration. Modeling ionization dynamics in molecular systems from first-principles can be challenging due to the large spatial extent of the wavefunction which stresses the accuracy of basis sets, and the intense fields which require non-perturbative time-dependent electronic structure methods. In this paper, we develop a time-dependent density functional theory approach which uses a Gaussian-type orbital (GTO) basis set to capture strong-field ionization rates and dynamics in atoms and small molecules. This involves propagating the electronic density matrix in time with a time-dependent laser potential and a spatial non-Hermitian complex absorbing potential which is projected onto an atom-centered basis set to remove ionized charge from the simulation. For the density functional theory (DFT) functional we use a tuned range-separated functional LC-PBE*, which has the correct asymptotic 1/r form of the potential and a reduced delocalization error compared to traditional DFT functionals. Ionization rates are computed for hydrogen, molecular nitrogen, and iodoacetylene under various field frequencies, intensities, and polarizations (angle-dependent ionization), and the results are shown to quantitatively agree with time-dependent Schrödinger equation and strong-field approximation calculations. This tuned DFT with GTO method opens the door to predictive all-electron time-dependent density functional theory simulations of ionization and ionization-triggered dynamics in molecular systems using tuned range-separated hybrid functionals.

Angle-dependent strong-field molecular ionization rates with tuned range-separated time-dependent density functional theory

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

Sissay, Adonay; Abanador, Paul; Mauger, François

2016-09-07

Strong-field ionization and the resulting electronic dynamics are important for a range of processes such as high harmonic generation, photodamage, charge resonance enhanced ionization, and ionization-triggered charge migration. Modeling ionization dynamics in molecular systems from first-principles can be challenging due to the large spatial extent of the wavefunction which stresses the accuracy of basis sets, and the intense fields which require non-perturbative time-dependent electronic structure methods. In this paper, we develop a time-dependent density functional theory approach which uses a Gaussian-type orbital (GTO) basis set to capture strong-field ionization rates and dynamics in atoms and small molecules. This involves propagatingmore » the electronic density matrix in time with a time-dependent laser potential and a spatial non-Hermitian complex absorbing potential which is projected onto an atom-centered basis set to remove ionized charge from the simulation. For the density functional theory (DFT) functional we use a tuned range-separated functional LC-PBE*, which has the correct asymptotic 1/r form of the potential and a reduced delocalization error compared to traditional DFT functionals. Ionization rates are computed for hydrogen, molecular nitrogen, and iodoacetylene under various field frequencies, intensities, and polarizations (angle-dependent ionization), and the results are shown to quantitatively agree with time-dependent Schrödinger equation and strong-field approximation calculations. This tuned DFT with GTO method opens the door to predictive all-electron time-dependent density functional theory simulations of ionization and ionization-triggered dynamics in molecular systems using tuned range-separated hybrid functionals.« less

Spousal Associations Between Functional Limitation and Depressive Symptom Trajectories: Longitudinal Findings from the Study of Asset and Health Dynamics Among the Oldest Old (AHEAD)

PubMed Central

Hoppmann, Christiane A.; Gerstorf, Denis; Hibbert, Anita

2010-01-01

Objective To examine spousal associations between functional limitation and depressive symptom trajectories in a national sample of older long-term married couples. Design We use 14.5-year longitudinal data on functional limitations and depressive symptoms from 1,704 couples participating in the Study of Asset and Health Dynamics Among the Oldest Old (AHEAD). Main Outcome Measures Activities of Daily Living and a short version of the Center for Epidemiologic Studies Depression Scale were used. Results Between-person difference findings corroborate previous research by showing that levels and changes in functional limitations and depressive symptoms are closely interrelated among wives and husbands. Importantly, our results further demonstrate sizeable associations in levels and changes in functional limitations and depressive symptoms between spouses. For example, functional limitation levels in one spouse were associated with depressive symptom levels in the respective other spouse. Spousal associations remained after controlling for individual (age, education, cognition) and spousal covariates (marriage duration, number of children) and did not differ between women and men. Conclusion Our findings highlight the important role of marital relationships in shaping health trajectories in old age because they show that some of the well-documented between-person differences in functional limitations and depressive symptoms are in fact related to spouses. PMID:21401249

Structures composing protein domains.

PubMed

Kubrycht, Jaroslav; Sigler, Karel; Souček, Pavel; Hudeček, Jiří

2013-08-01

This review summarizes available data concerning intradomain structures (IS) such as functionally important amino acid residues, short linear motifs, conserved or disordered regions, peptide repeats, broadly occurring secondary structures or folds, etc. IS form structural features (units or elements) necessary for interactions with proteins or non-peptidic ligands, enzyme reactions and some structural properties of proteins. These features have often been related to a single structural level (e.g. primary structure) mostly requiring certain structural context of other levels (e.g. secondary structures or supersecondary folds) as follows also from some examples reported or demonstrated here. In addition, we deal with some functionally important dynamic properties of IS (e.g. flexibility and different forms of accessibility), and more special dynamic changes of IS during enzyme reactions and allosteric regulation. Selected notes concern also some experimental methods, still more necessary tools of bioinformatic processing and clinically interesting relationships. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

An Overview of Dynamic Contact Resistance Measurement of HV Circuit Breakers

NASA Astrophysics Data System (ADS)

Bhole, A. A.; Gandhare, W. Z.

2016-06-01

With the deregulation of the electrical power industry, utilities and service companies are operating in a changing business environment. High voltage circuit breakers are extremely important for the function of modern electric power supply systems. The need to predict the proper function of circuit breaker grew over the years as the transmission networks expanded. The maintenance of circuit breakers deserves special consideration because of their importance for routine switching and for protection of other equipments. Electric transmission system breakups and equipment destruction can occur if a circuit breaker fails to operate because of a lack of preventive maintenance. Dynamic Contact Resistance Measurement (DCRM) is known as an effective technique for assessing the condition of power circuit breakers contacts and operating mechanism. This paper gives a general review about DCRM. It discusses the practical case studies on use of DCRM for condition assessment of high voltage circuit breakers.

Allosteric Pathways in the PPARγ-RXRα nuclear receptor complex

NASA Astrophysics Data System (ADS)

Ricci, Clarisse G.; Silveira, Rodrigo L.; Rivalta, Ivan; Batista, Victor S.; Skaf, Munir S.

2016-01-01

Understanding the nature of allostery in DNA-nuclear receptor (NR) complexes is of fundamental importance for drug development since NRs regulate the transcription of a myriad of genes in humans and other metazoans. Here, we investigate allostery in the peroxisome proliferator-activated/retinoid X receptor heterodimer. This important NR complex is a target for antidiabetic drugs since it binds to DNA and functions as a transcription factor essential for insulin sensitization and lipid metabolism. We find evidence of interdependent motions of Ω-loops and PPARγ-DNA binding domain with contacts susceptible to conformational changes and mutations, critical for regulating transcriptional functions in response to sequence-dependent DNA dynamics. Statistical network analysis of the correlated motions, observed in molecular dynamics simulations, shows preferential allosteric pathways with convergence centers comprised of polar amino acid residues. These findings are particularly relevant for the design of allosteric modulators of ligand-dependent transcription factors.

The fractal geometry of Hartree-Fock

NASA Astrophysics Data System (ADS)

Theel, Friethjof; Karamatskou, Antonia; Santra, Robin

2017-12-01

The Hartree-Fock method is an important approximation for the ground-state electronic wave function of atoms and molecules so that its usage is widespread in computational chemistry and physics. The Hartree-Fock method is an iterative procedure in which the electronic wave functions of the occupied orbitals are determined. The set of functions found in one step builds the basis for the next iteration step. In this work, we interpret the Hartree-Fock method as a dynamical system since dynamical systems are iterations where iteration steps represent the time development of the system, as encountered in the theory of fractals. The focus is put on the convergence behavior of the dynamical system as a function of a suitable control parameter. In our case, a complex parameter λ controls the strength of the electron-electron interaction. An investigation of the convergence behavior depending on the parameter λ is performed for helium, neon, and argon. We observe fractal structures in the complex λ-plane, which resemble the well-known Mandelbrot set, determine their fractal dimension, and find that with increasing nuclear charge, the fragmentation increases as well.

The function of neurocognitive networks. Comment on “Understanding brain networks and brain organization” by Pessoa

NASA Astrophysics Data System (ADS)

Bressler, Steven L.

2014-09-01

Pessoa [5] has performed a valuable service by reviewing the extant literature on brain networks and making a number of interesting proposals about their cognitive function. The term function is at the core of understanding the brain networks of cognition, or neurocognitive networks (NCNs) [1]. The great Russian neuropsychologist, Luria [4], defined brain function as the common task executed by a distributed brain network of complex dynamic structures united by the demands of cognition. Casting Luria in a modern light, we can say that function emerges from the interactions of brain regions in NCNs as they dynamically self-organize according to cognitive demands. Pessoa rightly details the mapping between brain function and structure, emphasizing both its pluripotency (one structure having multiple functions) and degeneracy (many structures having the same function). However, he fails to consider the potential importance of a one-to-one mapping between NCNs and function. If NCNs are uniquely composed of specific collections of brain areas, then each NCN has a unique function determined by that composition.

How do ensembles occupy space?

NASA Astrophysics Data System (ADS)

Daffertshofer, A.

2008-04-01

To find an answer to the title question, an attractiveness function between agents and locations is introduced yielding a phenomenological but generic model for the search for optimal distributions of agents over space. Agents can be seen as, e.g., members of biological populations like colonies of bacteria, swarms, and so on. The global attractiveness between agents and locations is maximized causing (self-propelled) `motion' of agents and, eventually, distinct distributions of agents over space. At the same token spontaneous changes or `decisions' are realized via competitions between agents as well as between locations. Hence, the model's solutions can be considered a sequence of decisions of agents during their search for a proper location. Depending on initial conditions both optimal as well as suboptimal configurations can be reached. For the latter early decision-making are important for avoiding possible conflicts: if the proper moment is missed, then only a few agents can find an optimal solution. Indeed, there is a delicate interplay between the values of the attractiveness function and the constraints as can be expressed by distinct terms of a potential function containing different Lagrange parameters. The model should be viewed as a top-down approach as it describes the dynamics of order parameters, i.e. macroscopic variables that reflect affiliations between agents and locations. The dynamics, however, is modified via so-called cost functions that are interpreted in terms of affinity levels. This interpretation can be seen as an original step towards an understanding of the dynamics at the underlying microscopic level. When focusing on the agent, one may say that the dynamics of an order parameter shows the evolution of an agent's intrinsic `map' for solving the problem of space occupation. Importantly, the dynamics does not necessarily distinguish between evolving (or moving) agents and evolving (or moving) locations though agents are more likely to be actors than the locations. Put differently, an order parameter describes an internal map which is linked to the expectation of an agent to find a certain location. Owing to the dynamical representation, we can therefore follow up the change of these maps over time leading from uncertainty to certainty.

Anatomy and physiology of the cornea.

PubMed

DelMonte, Derek W; Kim, Terry

2011-03-01

The importance of the cornea to the ocular structure and visual system is often overlooked because of the cornea's unassuming transparent nature. The cornea lacks the neurobiological sophistication of the retina and the dynamic movement of the lens; yet, without its clarity, the eye would not be able to perform its necessary functions. The complexity of structure and function necessary to maintain such elegant simplicity is the wonder that draws us to one of the most important components of our visual system. Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Structure and dynamics of water inside endohedrally functionalized carbon nanotubes.

PubMed

Paul, Sanjib; Abi, T G; Taraphder, Srabani

2014-05-14

We have carried out classical molecular dynamics simulations on the formation of extended water chains inside single-walled carbon nanotubes (SWCNTs) in water in the presence of selected functional groups covalently attached to the inner wall of the tube. Analogues of polar amino acid sidechains have been chosen to carry out the endohedral functionalization of SWCNTs. Our results show a spontaneous and asymmetric filling of the nanotube with dynamical water chains in all the cases studied. The presence of Asp- and Glu-like sidechains is found to result in the formation of well-ordered water chains across the tube having the maximum number of water molecules being retained within the core with the largest residence times. The presence of methyl or methylene groups along the suspended chain is observed to disrupt the formation of water chains with higher length and/or longer residence times. The importance of hydrogen bonding in forming these water chains is assessed in terms of the relaxations of different hydrogen bond correlation functions. For a given dimension of the hydrophobic nanopore, we thus obtain a scale comparing the ability of carboxylic, alcohol, and imidazole groups in controlling the structure and dynamics of water in it. Our results also suggest that SWCNTs of varying lengths, endohedrally functionalized with Asp- and Glu-like sidechains, may be used as design templates in CNT-based water storage devices.

De Novo Proteins with Life-Sustaining Functions Are Structurally Dynamic.

PubMed

Murphy, Grant S; Greisman, Jack B; Hecht, Michael H

2016-01-29

Designing and producing novel proteins that fold into stable structures and provide essential biological functions are key goals in synthetic biology. In initial steps toward achieving these goals, we constructed a combinatorial library of de novo proteins designed to fold into 4-helix bundles. As described previously, screening this library for sequences that function in vivo to rescue conditionally lethal mutants of Escherichia coli (auxotrophs) yielded several de novo sequences, termed SynRescue proteins, which rescued four different E. coli auxotrophs. In an effort to understand the structural requirements necessary for auxotroph rescue, we investigated the biophysical properties of the SynRescue proteins, using both computational and experimental approaches. Results from circular dichroism, size-exclusion chromatography, and NMR demonstrate that the SynRescue proteins are α-helical and relatively stable. Surprisingly, however, they do not form well-ordered structures. Instead, they form dynamic structures that fluctuate between monomeric and dimeric states. These findings show that a well-ordered structure is not a prerequisite for life-sustaining functions, and suggests that dynamic structures may have been important in the early evolution of protein function. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dynamical Constants and Time Universals: A First Step toward a Metrical Definition of Ordered and Abnormal Cognition.

PubMed

Elliott, Mark A; du Bois, Naomi

2017-01-01

From the point of view of the cognitive dynamicist the organization of brain circuitry into assemblies defined by their synchrony at particular (and precise) oscillation frequencies is important for the correct correlation of all independent cortical responses to the different aspects of a given complex thought or object. From the point of view of anyone operating complex mechanical systems, i.e., those comprising independent components that are required to interact precisely in time, it follows that the precise timing of such a system is essential - not only essential but measurable, and scalable. It must also be reliable over observations to bring about consistent behavior, whatever that behavior is. The catastrophic consequence of an absence of such precision, for instance that required to govern the interference engine in many automobiles, is indicative of how important timing is for the function of dynamical systems at all levels of operation. The dynamics and temporal considerations combined indicate that it is necessary to consider the operating characteristic of any dynamical, cognitive brain system in terms, superficially at least, of oscillation frequencies. These may, themselves, be forensic of an underlying time-related taxonomy. Currently there are only two sets of relevant and necessarily systematic observations in this field: one of these reports the precise dynamical structure of the perceptual systems engaged in dynamical binding across form and time; the second, derived both empirically from perceptual performance data, as well as obtained from theoretical models, demonstrates a timing taxonomy related to a fundamental operator referred to as the time quantum. In this contribution both sets of theory and observations are reviewed and compared for their predictive consistency. Conclusions about direct comparability are discussed for both theories of cognitive dynamics and time quantum models. Finally, a brief review of some experimental data measuring sensitivity to visual information presented to the visual blind field (blindsight), as well as from studies of temporal processing in autism and schizophrenia, indicates that an understanding of a precise and metrical dynamic structure may be very important for an operational understanding of perception as well as more general cognitive function in psychopathology.

Functional Roles of Slow Enzyme Conformational Changes in Network Dynamics

PubMed Central

Wu, Zhanghan; Xing, Jianhua

2012-01-01

Extensive studies from different fields reveal that many macromolecules, especially enzymes, show slow transitions among different conformations. This phenomenon is named such things as dynamic disorder, heterogeneity, hysteretic or mnemonic enzymes across these different fields, and has been directly demonstrated by single molecule enzymology and NMR studies recently. We analyzed enzyme slow conformational changes in the context of regulatory networks. A single enzymatic reaction with slow conformational changes can filter upstream network noises, and can either resonantly respond to the system stimulus at certain frequencies or respond adaptively for sustained input signals of the network fluctuations. It thus can serve as a basic functional motif with properties that are normally for larger intermolecular networks in the field of systems biology. We further analyzed examples including enzymes functioning against pH fluctuations, metabolic state change of Artemia embryos, and kinetic insulation of fluctuations in metabolic networks. The study also suggests that hysteretic enzymes may be building blocks of synthetic networks with various properties such as narrow-banded filtering. The work fills the missing gap between studies on enzyme biophysics and network level dynamics, and reveals that the coupling between the two is functionally important; it also suggests that the conformational dynamics of some enzymes may be evolutionally selected. PMID:23009855

Structure-Functional Basis of Ion Transport in Sodium–Calcium Exchanger (NCX) Proteins

PubMed Central

Giladi, Moshe; Shor, Reut; Lisnyansky, Michal; Khananshvili, Daniel

2016-01-01

The membrane-bound sodium–calcium exchanger (NCX) proteins shape Ca2+ homeostasis in many cell types, thus participating in a wide range of physiological and pathological processes. Determination of the crystal structure of an archaeal NCX (NCX_Mj) paved the way for a thorough and systematic investigation of ion transport mechanisms in NCX proteins. Here, we review the data gathered from the X-ray crystallography, molecular dynamics simulations, hydrogen–deuterium exchange mass-spectrometry (HDX-MS), and ion-flux analyses of mutants. Strikingly, the apo NCX_Mj protein exhibits characteristic patterns in the local backbone dynamics at particular helix segments, thereby possessing characteristic HDX profiles, suggesting structure-dynamic preorganization (geometric arrangements of catalytic residues before the transition state) of conserved α1 and α2 repeats at ion-coordinating residues involved in transport activities. Moreover, dynamic preorganization of local structural entities in the apo protein predefines the status of ion-occlusion and transition states, even though Na+ or Ca2+ binding modifies the preceding backbone dynamics nearby functionally important residues. Future challenges include resolving the structural-dynamic determinants governing the ion selectivity, functional asymmetry and ion-induced alternating access. Taking into account the structural similarities of NCX_Mj with the other proteins belonging to the Ca2+/cation exchanger superfamily, the recent findings can significantly improve our understanding of ion transport mechanisms in NCX and similar proteins. PMID:27879668

Structure-Functional Basis of Ion Transport in Sodium-Calcium Exchanger (NCX) Proteins.

PubMed

Giladi, Moshe; Shor, Reut; Lisnyansky, Michal; Khananshvili, Daniel

2016-11-22

The membrane-bound sodium-calcium exchanger (NCX) proteins shape Ca 2+ homeostasis in many cell types, thus participating in a wide range of physiological and pathological processes. Determination of the crystal structure of an archaeal NCX (NCX_Mj) paved the way for a thorough and systematic investigation of ion transport mechanisms in NCX proteins. Here, we review the data gathered from the X-ray crystallography, molecular dynamics simulations, hydrogen-deuterium exchange mass-spectrometry (HDX-MS), and ion-flux analyses of mutants. Strikingly, the apo NCX_Mj protein exhibits characteristic patterns in the local backbone dynamics at particular helix segments, thereby possessing characteristic HDX profiles, suggesting structure-dynamic preorganization (geometric arrangements of catalytic residues before the transition state) of conserved α₁ and α₂ repeats at ion-coordinating residues involved in transport activities. Moreover, dynamic preorganization of local structural entities in the apo protein predefines the status of ion-occlusion and transition states, even though Na⁺ or Ca 2+ binding modifies the preceding backbone dynamics nearby functionally important residues. Future challenges include resolving the structural-dynamic determinants governing the ion selectivity, functional asymmetry and ion-induced alternating access. Taking into account the structural similarities of NCX_Mj with the other proteins belonging to the Ca 2+ /cation exchanger superfamily, the recent findings can significantly improve our understanding of ion transport mechanisms in NCX and similar proteins.

Multiscale simulations of patchy particle systems combining Molecular Dynamics, Path Sampling and Green's Function Reaction Dynamics

NASA Astrophysics Data System (ADS)

Bolhuis, Peter

Important reaction-diffusion processes, such as biochemical networks in living cells, or self-assembling soft matter, span many orders in length and time scales. In these systems, the reactants' spatial dynamics at mesoscopic length and time scales of microns and seconds is coupled to the reactions between the molecules at microscopic length and time scales of nanometers and milliseconds. This wide range of length and time scales makes these systems notoriously difficult to simulate. While mean-field rate equations cannot describe such processes, the mesoscopic Green's Function Reaction Dynamics (GFRD) method enables efficient simulation at the particle level provided the microscopic dynamics can be integrated out. Yet, many processes exhibit non-trivial microscopic dynamics that can qualitatively change the macroscopic behavior, calling for an atomistic, microscopic description. The recently developed multiscale Molecular Dynamics Green's Function Reaction Dynamics (MD-GFRD) approach combines GFRD for simulating the system at the mesocopic scale where particles are far apart, with microscopic Molecular (or Brownian) Dynamics, for simulating the system at the microscopic scale where reactants are in close proximity. The association and dissociation of particles are treated with rare event path sampling techniques. I will illustrate the efficiency of this method for patchy particle systems. Replacing the microscopic regime with a Markov State Model avoids the microscopic regime completely. The MSM is then pre-computed using advanced path-sampling techniques such as multistate transition interface sampling. I illustrate this approach on patchy particle systems that show multiple modes of binding. MD-GFRD is generic, and can be used to efficiently simulate reaction-diffusion systems at the particle level, including the orientational dynamics, opening up the possibility for large-scale simulations of e.g. protein signaling networks.

Protein dynamics and motions in relation to their functions: several case studies and the underlying mechanisms

PubMed Central

Yang, Li-Quan; Sang, Peng; Tao, Yan; Fu, Yun-Xin; Zhang, Ke-Qin; Xie, Yue-Hui; Liu, Shu-Qun

2013-01-01

Proteins are dynamic entities in cellular solution with functions governed essentially by their dynamic personalities. We review several dynamics studies on serine protease proteinase K and HIV-1 gp120 envelope glycoprotein to demonstrate the importance of investigating the dynamic behaviors and molecular motions for a complete understanding of their structure–function relationships. Using computer simulations and essential dynamic (ED) analysis approaches, the dynamics data obtained revealed that: (i) proteinase K has highly flexible substrate-binding site, thus supporting the induced-fit or conformational selection mechanism of substrate binding; (ii) Ca2+ removal from proteinase K increases the global conformational flexibility, decreases the local flexibility of substrate-binding region, and does not influence the thermal motion of catalytic triad, thus explaining the experimentally determined decreased thermal stability, reduced substrate affinity, and almost unchanged catalytic activity upon Ca2+ removal; (iii) substrate binding affects the large concerted motions of proteinase K, and the resulting dynamic pocket can be connected to substrate binding, orientation, and product release; (iv) amino acid mutations 375 S/W and 423 I/P of HIV-1 gp120 have distinct effects on molecular motions of gp120, facilitating 375 S/W mutant to assume the CD4-bound conformation, while 423 I/P mutant to prefer for CD4-unliganded state. The mechanisms underlying protein dynamics and protein–ligand binding, including the concept of the free energy landscape (FEL) of the protein–solvent system, how the ruggedness and variability of FEL determine protein's dynamics, and how the three ligand-binding models, the lock-and-key, induced-fit, and conformational selection are rationalized based on the FEL theory are discussed in depth. PMID:23527883

Protein dynamics and motions in relation to their functions: several case studies and the underlying mechanisms.

PubMed

Yang, Li-Quan; Sang, Peng; Tao, Yan; Fu, Yun-Xin; Zhang, Ke-Qin; Xie, Yue-Hui; Liu, Shu-Qun

2014-01-01

Proteins are dynamic entities in cellular solution with functions governed essentially by their dynamic personalities. We review several dynamics studies on serine protease proteinase K and HIV-1 gp120 envelope glycoprotein to demonstrate the importance of investigating the dynamic behaviors and molecular motions for a complete understanding of their structure-function relationships. Using computer simulations and essential dynamic (ED) analysis approaches, the dynamics data obtained revealed that: (i) proteinase K has highly flexible substrate-binding site, thus supporting the induced-fit or conformational selection mechanism of substrate binding; (ii) Ca(2+) removal from proteinase K increases the global conformational flexibility, decreases the local flexibility of substrate-binding region, and does not influence the thermal motion of catalytic triad, thus explaining the experimentally determined decreased thermal stability, reduced substrate affinity, and almost unchanged catalytic activity upon Ca(2+) removal; (iii) substrate binding affects the large concerted motions of proteinase K, and the resulting dynamic pocket can be connected to substrate binding, orientation, and product release; (iv) amino acid mutations 375 S/W and 423 I/P of HIV-1 gp120 have distinct effects on molecular motions of gp120, facilitating 375 S/W mutant to assume the CD4-bound conformation, while 423 I/P mutant to prefer for CD4-unliganded state. The mechanisms underlying protein dynamics and protein-ligand binding, including the concept of the free energy landscape (FEL) of the protein-solvent system, how the ruggedness and variability of FEL determine protein's dynamics, and how the three ligand-binding models, the lock-and-key, induced-fit, and conformational selection are rationalized based on the FEL theory are discussed in depth.

Age-Related Locomotion Characteristics in Association with Balance Function in Young, Middle-Aged, and Older Adults.

PubMed

Lee, Hwang-Jae; Chang, Won Hyuk; Hwang, Sun Hee; Choi, Byung-Ok; Ryu, Gyu-Ha; Kim, Yun-Hee

2017-04-01

The purpose of this study was to examine age-related gait characteristics and their associations with balance function in older adults. A total of 51 adult volunteers participated. All subjects underwent locomotion analysis using a 3D motion analysis and 12-channel dynamic electromyography system. Dynamic balance function was assessed by the Berg Balance Scale. Older adults showed a higher level of muscle activation than young adults, and there were significant positive correlations between increased age and activation of the trunk and thigh muscles in the stance and swing phase of the gait cycle. In particular, back extensor muscle activity was mostly correlated with the dynamic balance in older adults. Thus, back extensor muscle activity in walking may provide a clue for higher falling risk in older adults. This study demonstrates that the back extensor muscles play very important roles with potential for rehabilitation training to improve balance and gait in older adults.

Non-linear corrections to the time-covariance function derived from a multi-state chemical master equation.

PubMed

Scott, M

2012-08-01

The time-covariance function captures the dynamics of biochemical fluctuations and contains important information about the underlying kinetic rate parameters. Intrinsic fluctuations in biochemical reaction networks are typically modelled using a master equation formalism. In general, the equation cannot be solved exactly and approximation methods are required. For small fluctuations close to equilibrium, a linearisation of the dynamics provides a very good description of the relaxation of the time-covariance function. As the number of molecules in the system decrease, deviations from the linear theory appear. Carrying out a systematic perturbation expansion of the master equation to capture these effects results in formidable algebra; however, symbolic mathematics packages considerably expedite the computation. The authors demonstrate that non-linear effects can reveal features of the underlying dynamics, such as reaction stoichiometry, not available in linearised theory. Furthermore, in models that exhibit noise-induced oscillations, non-linear corrections result in a shift in the base frequency along with the appearance of a secondary harmonic.

Dynamic balance of excitation and inhibition rapidly modulates spike probability and precision in feed-forward hippocampal circuits

PubMed Central

Wahlstrom-Helgren, Sarah

2016-01-01

Feed-forward inhibitory (FFI) circuits are important for many information-processing functions. FFI circuit operations critically depend on the balance and timing between the excitatory and inhibitory components, which undergo rapid dynamic changes during neural activity due to short-term plasticity (STP) of both components. How dynamic changes in excitation/inhibition (E/I) balance during spike trains influence FFI circuit operations remains poorly understood. In the current study we examined the role of STP in the FFI circuit functions in the mouse hippocampus. Using a coincidence detection paradigm with simultaneous activation of two Schaffer collateral inputs, we found that the spiking probability in the target CA1 neuron was increased while spike precision concomitantly decreased during high-frequency bursts compared with a single spike. Blocking inhibitory synaptic transmission revealed that dynamics of inhibition predominately modulates the spike precision but not the changes in spiking probability, whereas the latter is modulated by the dynamics of excitation. Further analyses combining whole cell recordings and simulations of the FFI circuit suggested that dynamics of the inhibitory circuit component may influence spiking behavior during bursts by broadening the width of excitatory postsynaptic responses and that the strength of this modulation depends on the basal E/I ratio. We verified these predictions using a mouse model of fragile X syndrome, which has an elevated E/I ratio, and found a strongly reduced modulation of postsynaptic response width during bursts. Our results suggest that changes in the dynamics of excitatory and inhibitory circuit components due to STP play important yet distinct roles in modulating the properties of FFI circuits. PMID:27605532

Calculation of broadband time histories of ground motion, Part II: Kinematic and dynamic modeling using theoretical Green's functions and comparison with the 1994 northridge earthquake

USGS Publications Warehouse

Hartzell, S.; Guatteri, Mariagiovanna; Mai, P.M.; Liu, P.-C.; Fisk, M. R.

2005-01-01

In the evolution of methods for calculating synthetic time histories of ground motion for postulated earthquakes, kinematic source models have dominated to date because of their ease of application. Dynamic models, however, which incorporate a physical relationship between important faulting parameters of stress drop, slip, rupture velocity, and rise time, are becoming more accessible. This article compares a class of kinematic models based on the summation of a fractal distribution of subevent sizes with a dynamic model based on the slip-weakening friction law. Kinematic modeling is done for the frequency band 0.2 to 10.0. Hz, dynamic models are calculated from 0.2 to 2.0. Hz. The strong motion data set for the 1994 Northridge earthquake is used to evaluate and compare the synthetic time histories. Source models are propagated to the far field by convolution with 1D and 3D theoretical Green’s functions. In addition, the kinematic model is used to evaluate the importance of propagation path effects: velocity structure, scattering, and nonlinearity. At present, the kinematic model gives a better broadband fit to the Northridge ground motion than the simple slip-weakening dynamic model. In general, the dynamic model overpredicts rise times and produces insufficient shorter-period energy. Within the context of the slip-weakening model, the Northridge ground motion requires a short slip-weakening distance, on the order of 0.15 m or less. A more complex dynamic model including rate weakening or one that allows shorter rise times near the hypocenter may fit the data better.

Light, Molecules, Action: Broadband UV-visible transient absorption studies of excited state dynamics in photoactive molecules

NASA Astrophysics Data System (ADS)

Sension, Roseanne

2015-03-01

Broadband UV-visible transient absorption spectroscopy provides a powerful tool for the investigation of the dynamics of electronically excited molecules in the condensed phase. It is now possible to obtain transient spectra on a routine basis spanning the range from <300 nm to >800 nm with femtosecond time resolution. We have used this method to study the excited state dynamics and internal conversion of a range of molecular systems with potential application as optically powered molecular devices. The cyclohexadiene ring-opening reaction is the basis of a class of important optical switches and of the biological synthesis of previtamin D3. The ring-opening reaction is ultrafast, occurring on a picosecond to subpicosecond times scale depending on the substituents around the ring. These have a significant influence on the dynamics and electronic structure of the electronically excited molecule. The results of a series of transient absorption studies as a function of chromophore substitution and environment will be presented. The cis-trans isomerization of polyene molecules, especially substituted stilbenes, provides another important class of functional molecular transformations. Again the excited state dynamics can be ultrafast with photochemistry controlled by details of the curve crossings and conical intersections. Finally the photochemistry of the even more complex set of cobalamin chromophores with a photoalabile C-Co bond has been proposed as a tool for spatio-temporal control of molecule delivery including drug delivery. Broadband transient absorption spectroscopy has been used to investigate the ultrafast electronic dynamics of a range of cobalamin compounds with comparison to detailed theoretical calculations. The results of these studies will be presented.

Quantitative Analysis of Cellular Metabolic Dissipative, Self-Organized Structures

PubMed Central

de la Fuente, Ildefonso Martínez

2010-01-01

One of the most important goals of the postgenomic era is understanding the metabolic dynamic processes and the functional structures generated by them. Extensive studies during the last three decades have shown that the dissipative self-organization of the functional enzymatic associations, the catalytic reactions produced during the metabolite channeling, the microcompartmentalization of these metabolic processes and the emergence of dissipative networks are the fundamental elements of the dynamical organization of cell metabolism. Here we present an overview of how mathematical models can be used to address the properties of dissipative metabolic structures at different organizational levels, both for individual enzymatic associations and for enzymatic networks. Recent analyses performed with dissipative metabolic networks have shown that unicellular organisms display a singular global enzymatic structure common to all living cellular organisms, which seems to be an intrinsic property of the functional metabolism as a whole. Mathematical models firmly based on experiments and their corresponding computational approaches are needed to fully grasp the molecular mechanisms of metabolic dynamical processes. They are necessary to enable the quantitative and qualitative analysis of the cellular catalytic reactions and also to help comprehend the conditions under which the structural dynamical phenomena and biological rhythms arise. Understanding the molecular mechanisms responsible for the metabolic dissipative structures is crucial for unraveling the dynamics of cellular life. PMID:20957111

Mouthpart separation does not impede butterfly feeding.

PubMed

Lehnert, Matthew S; Mulvane, Catherine P; Brothers, Aubrey

2014-03-01

The functionality of butterfly mouthparts (proboscis) plays an important role in pollination systems, which is driven by the reward of nectar. Proboscis functionality has been assumed to require action of the sucking pump in the butterfly's head coupled with the straw-like structure. Proper proboscis functionality, however, also is dependent on capillarity and wettability dynamics that facilitate acquisition of liquid films from porous substrates. Due to the importance of wettability dynamics in proboscis functionality, we hypothesized that proboscides of eastern black swallowtail (Papilio polyxenes asterius Stoll) (Papilionidae) and cabbage butterflies (Pieris rapae Linnaeus) (Pieridae) that were experimentally split (i.e., proboscides no longer resembling a sealed straw-like tube) would retain the ability to feed. Proboscides were split either in the drinking region (distal 6-10% of proboscis length) or approximately 50% of the proboscis length 24 h before feeding trials when butterflies were fed a red food-coloring solution. Approximately 67% of the butterflies with proboscides split reassembled prior to the feeding trials and all of these butterflies displayed evidence of proboscis functionality. Butterflies with proboscides that did not reassemble also demonstrated fluid uptake capabilities, thus suggesting that wild butterflies might retain fluid uptake capabilities, even when the proboscis is partially injured. Copyright © 2013 Elsevier Ltd. All rights reserved.

Functional importance of blood flow dynamics and partial oxygen pressure in the anterior pituitary.

PubMed

Schaeffer, Marie; Hodson, David J; Lafont, Chrystel; Mollard, Patrice

2010-12-01

The pulsatile release of hormone is obligatory for the control of a range of important body homeostatic functions. To generate these pulses, endocrine organs have developed finely regulated mechanisms to modulate blood flow both to meet the metabolic demand associated with intense endocrine cell activity and to ensure the temporally precise uptake of secreted hormone into the bloodstream. With a particular focus on the pituitary gland as a model system, we review here the importance of the interplay between blood flow regulation and oxygen tensions in the functioning of endocrine systems, and the known regulatory signals involved in the modification of flow patterns under both normal physiological and pathological conditions. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Determining the Ecosystem Services Important for Urban Landscapes

EPA Science Inventory

Urban ecosystems present special considerations and challenges in researching and evaluating ecosystem functions and services. A case study of nitrate retention and loss in forested, urban wetlands illustrates these challenges. Water table dynamics, in situ nitrogen cy...

Particulate organic matter dynamics in ephemeral tributaries of a Central Appalachian stream

EPA Science Inventory

Headwater ephemeral tributaries are external interfaces between uplands and downstream waters. Terrestrial particulate organic matter (POM) is important in fueling aquatic ecosystems, however the extent to which ephemeral tributaries are functionally connected to downstream water...

Why not energy conservation?

NASA Astrophysics Data System (ADS)

Carlson, Shawn

2016-01-01

Energy conservation is a deep principle that is obeyed by all of the fundamental forces of nature. It puts stringent constraints on all systems, particularly systems that are ‘isolated,’ meaning that no energy can enter or escape. Notwithstanding the success of the principle of stationary action, it is fair to wonder to what extent physics can be formulated from the principle of stationary energy. We show that if one interprets mechanical energy as a state function, then its stationarity leads to a novel formulation of classical mechanics. However, unlike Lagrangian and Hamiltonian mechanics, which deliver their state functions via algebraic proscriptions (i.e., the Lagrangian is always the difference between a system’s kinetic and potential energies), this new formalism identifies its state functions as the solutions to a differential equation. This is an important difference because differential equations can generate more general solutions than algebraic recipes. When applied to Newtonian systems for which the energy function is separable, these state functions are always the mechanical energy. However, while the stationary state function for a charged particle moving in an electromagnetic field proves not to be energy, the function nevertheless correctly encodes the dynamics of the system. Moreover, the stationary state function for a free relativistic particle proves not to be the energy either. Rather, our differential equation yields the relativistic free-particle Lagrangian (plus a non-dynamical constant) in its correct dynamical context. To explain how this new formalism can consistently deliver stationary state functions that give the correct dynamics but that are not always the mechanical energy, we propose that energy conservation is a specific realization of a deeper principle of stationarity that governs both relativistic and non-relativistic mechanics.

Stuck in a State of Inattention? Functional Hyperconnectivity as an Indicator of Disturbed Intrinsic Brain Dynamics in Adolescents With Concussion: A Pilot Study

PubMed Central

Virji-Babul, Naznin

2018-01-01

Sports-related concussion in youth is a major public health issue. Evaluating the diffuse and often subtle changes in structure and function that occur in the brain, particularly in this population, remains a significant challenge. The goal of this pilot study was to evaluate the relationship between the intrinsic dynamics of the brain using resting-state functional magnetic resonance imaging (rs-fMRI) and relate these findings to structural brain correlates from diffusion tensor imaging in a group of adolescents with sports-related concussions (n = 6) and a group of healthy adolescent athletes (n = 6). We analyzed rs-fMRI data using a sliding windows approach and related the functional findings to structural brain correlates by applying graph theory analysis to the diffusion tensor imaging data. Within the resting-state condition, we extracted three separate brain states in both groups. Our analysis revealed that the brain dynamics in healthy adolescents was characterized by a dynamic pattern, shifting equally between three brain states; however, in adolescents with concussion, the pattern was more static with a longer time spent in one brain state. Importantly, this lack of dynamic flexibility in the concussed group was associated with increased nodal strength in the left middle frontal gyrus, suggesting reorganization in a region related to attention. This preliminary report shows that both the intrinsic brain dynamics and structural organization are altered in networks related to attention in adolescents with concussion. This first report in adolescents will be used to inform future studies in a larger cohort. PMID:29357675

Stuck in a State of Inattention? Functional Hyperconnectivity as an Indicator of Disturbed Intrinsic Brain Dynamics in Adolescents With Concussion: A Pilot Study.

PubMed

Muller, Angela M; Virji-Babul, Naznin

2018-01-01

Sports-related concussion in youth is a major public health issue. Evaluating the diffuse and often subtle changes in structure and function that occur in the brain, particularly in this population, remains a significant challenge. The goal of this pilot study was to evaluate the relationship between the intrinsic dynamics of the brain using resting-state functional magnetic resonance imaging (rs-fMRI) and relate these findings to structural brain correlates from diffusion tensor imaging in a group of adolescents with sports-related concussions ( n = 6) and a group of healthy adolescent athletes ( n = 6). We analyzed rs-fMRI data using a sliding windows approach and related the functional findings to structural brain correlates by applying graph theory analysis to the diffusion tensor imaging data. Within the resting-state condition, we extracted three separate brain states in both groups. Our analysis revealed that the brain dynamics in healthy adolescents was characterized by a dynamic pattern, shifting equally between three brain states; however, in adolescents with concussion, the pattern was more static with a longer time spent in one brain state. Importantly, this lack of dynamic flexibility in the concussed group was associated with increased nodal strength in the left middle frontal gyrus, suggesting reorganization in a region related to attention. This preliminary report shows that both the intrinsic brain dynamics and structural organization are altered in networks related to attention in adolescents with concussion. This first report in adolescents will be used to inform future studies in a larger cohort.

A molecular dynamics study on sI hydrogen hydrate.

PubMed

Mondal, S; Ghosh, S; Chattaraj, P K

2013-07-01

A molecular dynamics simulation is carried out to explore the possibility of using sI clathrate hydrate as hydrogen storage material. Metastable hydrogen hydrate structures are generated using the LAMMPS software. Different binding energies and radial distribution functions provide important insights into the behavior of the various types of hydrogen and oxygen atoms present in the system. Clathrate hydrate cages become more stable in the presence of guest molecules like hydrogen.

Evol and ProDy for bridging protein sequence evolution and structural dynamics.

PubMed

Bakan, Ahmet; Dutta, Anindita; Mao, Wenzhi; Liu, Ying; Chennubhotla, Chakra; Lezon, Timothy R; Bahar, Ivet

2014-09-15

Correlations between sequence evolution and structural dynamics are of utmost importance in understanding the molecular mechanisms of function and their evolution. We have integrated Evol, a new package for fast and efficient comparative analysis of evolutionary patterns and conformational dynamics, into ProDy, a computational toolbox designed for inferring protein dynamics from experimental and theoretical data. Using information-theoretic approaches, Evol coanalyzes conservation and coevolution profiles extracted from multiple sequence alignments of protein families with their inferred dynamics. ProDy and Evol are open-source and freely available under MIT License from http://prody.csb.pitt.edu/. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Quantum critical point revisited by dynamical mean-field theory

NASA Astrophysics Data System (ADS)

Xu, Wenhu; Kotliar, Gabriel; Tsvelik, Alexei M.

2017-03-01

Dynamical mean-field theory is used to study the quantum critical point (QCP) in the doped Hubbard model on a square lattice. The QCP is characterized by a universal scaling form of the self-energy and a spin density wave instability at an incommensurate wave vector. The scaling form unifies the low-energy kink and the high-energy waterfall feature in the spectral function, while the spin dynamics includes both the critical incommensurate and high-energy antiferromagnetic paramagnons. We use the frequency-dependent four-point correlation function of spin operators to calculate the momentum-dependent correction to the electron self-energy. By comparing with the calculations based on the spin-fermion model, our results indicate the frequency dependence of the quasiparticle-paramagnon vertices is an important factor to capture the momentum dependence in quasiparticle scattering.

Lipid Interaction Sites on Channels, Transporters and Receptors: Recent Insights from Molecular Dynamics Simulations

PubMed Central

Hedger, George; Sansom, Mark S. P.

2017-01-01

Lipid molecules are able to selectively interact with specific sites on integral membrane proteins, and modulate their structure and function. Identification and characterisation of these sites is of importance for our understanding of the molecular basis of membrane protein function and stability, and may facilitate the design of lipid-like drug molecules. Molecular dynamics simulations provide a powerful tool for the identification of these sites, complementing advances in membrane protein structural biology and biophysics. We describe recent notable biomolecular simulation studies which have identified lipid interaction sites on a range of different membrane proteins. The sites identified in these simulation studies agree well with those identified by complementary experimental techniques. This demonstrates the power of the molecular dynamics approach in the prediction and characterization of lipid interaction sites on integral membrane proteins. PMID:26946244

Quantum critical point revisited by dynamical mean-field theory

DOE PAGES

Xu, Wenhu; Kotliar, Gabriel; Tsvelik, Alexei M.

2017-03-31

Dynamical mean-field theory is used to study the quantum critical point (QCP) in the doped Hubbard model on a square lattice. We characterize the QCP by a universal scaling form of the self-energy and a spin density wave instability at an incommensurate wave vector. The scaling form unifies the low-energy kink and the high-energy waterfall feature in the spectral function, while the spin dynamics includes both the critical incommensurate and high-energy antiferromagnetic paramagnons. Here, we use the frequency-dependent four-point correlation function of spin operators to calculate the momentum-dependent correction to the electron self-energy. Furthermore, by comparing with the calculations basedmore » on the spin-fermion model, our results indicate the frequency dependence of the quasiparticle-paramagnon vertices is an important factor to capture the momentum dependence in quasiparticle scattering.« less

Dynamic localization and interaction with other Bacillus subtilis actin-like proteins are important for the function of MreB.

PubMed

Defeu Soufo, Hervé Joël; Graumann, Peter L

2006-12-01

Bacterial actin-like proteins play a key role in cell morphology and in chromosome segregation. Many bacteria, like Bacillus subtilis, contain three genes encoding actin-like proteins, called mreB, mbl and mreBH in B. subtilis. We show that MreB and Mbl colocalize extensively within live cells, and that all three B. subtilis actin paralogues interact with each other underneath the cell membrane. A mutation in the phosphate 2 motif of MreB had a dominant negative effect on cell morphology and on chromosome segregation. Expression of this mutant allele of MreB interfered with the dynamic localization of Mbl. These experiments show that the interaction between MreB and Mbl has physiological significance. An mreB deletion strain can grow under special media conditions, however, depletion of Mbl in this mutant background abolished growth, indicating that actin paralogues can partially complement each other. The membrane protein MreC was found to interact with Mbl, but not with MreB, revealing a clear distinction between the function of the two paralogues. The phosphate 2 mutant MreB protein allowed for filament formation of mutant or wild-type MreB, but abolished the dynamic reorganization of the filaments. The latter mutation led to a strong reduction, but not complete loss, of function of MreB, both in terms of chromosome segregation and of cell morphology. Our work shows that that the dynamic localization of MreB is essential for the proper activity of the actin-like protein and that the interactions between MreB paralogues have important physiological significance.

Functional Connectivity among Spikes in Low Dimensional Space during Working Memory Task in Rat

PubMed Central

Tian, Xin

2014-01-01

Working memory (WM) is critically important in cognitive tasks. The functional connectivity has been a powerful tool for understanding the mechanism underlying the information processing during WM tasks. The aim of this study is to investigate how to effectively characterize the dynamic variations of the functional connectivity in low dimensional space among the principal components (PCs) which were extracted from the instantaneous firing rate series. Spikes were obtained from medial prefrontal cortex (mPFC) of rats with implanted microelectrode array and then transformed into continuous series via instantaneous firing rate method. Granger causality method is proposed to study the functional connectivity. Then three scalar metrics were applied to identify the changes of the reduced dimensionality functional network during working memory tasks: functional connectivity (GC), global efficiency (E) and casual density (CD). As a comparison, GC, E and CD were also calculated to describe the functional connectivity in the original space. The results showed that these network characteristics dynamically changed during the correct WM tasks. The measure values increased to maximum, and then decreased both in the original and in the reduced dimensionality. Besides, the feature values of the reduced dimensionality were significantly higher during the WM tasks than they were in the original space. These findings suggested that functional connectivity among the spikes varied dynamically during the WM tasks and could be described effectively in the low dimensional space. PMID:24658291

Hierarchical Feedback Modules and Reaction Hubs in Cell Signaling Networks

PubMed Central

Xu, Jianfeng; Lan, Yueheng

2015-01-01

Despite much effort, identification of modular structures and study of their organizing and functional roles remain a formidable challenge in molecular systems biology, which, however, is essential in reaching a systematic understanding of large-scale cell regulation networks and hence gaining capacity of exerting effective interference to cell activity. Combining graph theoretic methods with available dynamics information, we successfully retrieved multiple feedback modules of three important signaling networks. These feedbacks are structurally arranged in a hierarchical way and dynamically produce layered temporal profiles of output signals. We found that global and local feedbacks act in very different ways and on distinct features of the information flow conveyed by signal transduction but work highly coordinately to implement specific biological functions. The redundancy embodied with multiple signal-relaying channels and feedback controls bestow great robustness and the reaction hubs seated at junctions of different paths announce their paramount importance through exquisite parameter management. The current investigation reveals intriguing general features of the organization of cell signaling networks and their relevance to biological function, which may find interesting applications in analysis, design and control of bio-networks. PMID:25951347

Dynamical graph theory networks techniques for the analysis of sparse connectivity networks in dementia

NASA Astrophysics Data System (ADS)

Tahmassebi, Amirhessam; Pinker-Domenig, Katja; Wengert, Georg; Lobbes, Marc; Stadlbauer, Andreas; Romero, Francisco J.; Morales, Diego P.; Castillo, Encarnacion; Garcia, Antonio; Botella, Guillermo; Meyer-Bäse, Anke

2017-05-01

Graph network models in dementia have become an important computational technique in neuroscience to study fundamental organizational principles of brain structure and function of neurodegenerative diseases such as dementia. The graph connectivity is reflected in the connectome, the complete set of structural and functional connections of the graph network, which is mostly based on simple Pearson correlation links. In contrast to simple Pearson correlation networks, the partial correlations (PC) only identify direct correlations while indirect associations are eliminated. In addition to this, the state-of-the-art techniques in brain research are based on static graph theory, which is unable to capture the dynamic behavior of the brain connectivity, as it alters with disease evolution. We propose a new research avenue in neuroimaging connectomics based on combining dynamic graph network theory and modeling strategies at different time scales. We present the theoretical framework for area aggregation and time-scale modeling in brain networks as they pertain to disease evolution in dementia. This novel paradigm is extremely powerful, since we can derive both static parameters pertaining to node and area parameters, as well as dynamic parameters, such as system's eigenvalues. By implementing and analyzing dynamically both disease driven PC-networks and regular concentration networks, we reveal differences in the structure of these network that play an important role in the temporal evolution of this disease. The described research is key to advance biomedical research on novel disease prediction trajectories and dementia therapies.

The effect of subtalar inversion/eversion on the dynamic function of the tibialis anterior, soleus, and gastrocnemius during the stance phase of gait.

PubMed

Wang, Ruoli; Gutierrez-Farewik, Elena M

2011-05-01

The purpose of this study was to determine how gait deviation in one plane (i.e. excessive subtalar inversion/eversion) can affect the dynamic function of the tibialis anterior, gastrocnemius, and soleus to accelerate the subtalar, ankle, knee and hip joints, as well as the body center of mass. Induced acceleration analysis was performed based on a subject-specific three-dimensional linkage model configured by stance phase gait data and driven by one unit of muscle force. Eight healthy adult subjects were examined in gait analysis. The subtalar inversion/eversion was modeled by offsetting up to 20° from the normal subtalar angle while other configurations remained unaltered. This study showed that the gastrocnemius, soleus and tibialis anterior generally functioned as their anatomical definition in normal gait, but counterintuitive function was occasionally found in the bi-articular gastrocnemius. The plantarflexors play important roles in the body support and forward progression. Excessive subtalar eversion was found to enlarge the plantarflexors and tibialis anterior's function. Induced acceleration analysis demonstrated its ability to isolate the contributions of individual muscle to a given factor, and as a means of studying effect of pathological gait on the dynamic muscle functions. Copyright © 2011 Elsevier B.V. All rights reserved.

Dynamical influence processes on networks: general theory and applications to social contagion.

PubMed

Harris, Kameron Decker; Danforth, Christopher M; Dodds, Peter Sheridan

2013-08-01

We study binary state dynamics on a network where each node acts in response to the average state of its neighborhood. By allowing varying amounts of stochasticity in both the network and node responses, we find different outcomes in random and deterministic versions of the model. In the limit of a large, dense network, however, we show that these dynamics coincide. We construct a general mean-field theory for random networks and show this predicts that the dynamics on the network is a smoothed version of the average response function dynamics. Thus, the behavior of the system can range from steady state to chaotic depending on the response functions, network connectivity, and update synchronicity. As a specific example, we model the competing tendencies of imitation and nonconformity by incorporating an off-threshold into standard threshold models of social contagion. In this way, we attempt to capture important aspects of fashions and societal trends. We compare our theory to extensive simulations of this "limited imitation contagion" model on Poisson random graphs, finding agreement between the mean-field theory and stochastic simulations.

Exploring GPCR-Lipid Interactions by Molecular Dynamics Simulations: Excitements, Challenges, and the Way Forward.

PubMed

Sengupta, Durba; Prasanna, Xavier; Mohole, Madhura; Chattopadhyay, Amitabha

2018-06-07

Gprotein-coupled receptors (GPCRs) are seven transmembrane receptors that mediate a large number of cellular responses and are important drug targets. One of the current challenges in GPCR biology is to analyze the molecular signatures of receptor-lipid interactions and their subsequent effects on GPCR structure, organization, and function. Molecular dynamics simulation studies have been successful in predicting molecular determinants of receptor-lipid interactions. In particular, predicted cholesterol interaction sites appear to correspond well with experimentally determined binding sites and estimated time scales of association. In spite of several success stories, the methodologies in molecular dynamics simulations are still emerging. In this Feature Article, we provide a comprehensive overview of coarse-grain and atomistic molecular dynamics simulations of GPCR-lipid interaction in the context of experimental observations. In addition, we discuss the effect of secondary and tertiary structural constraints in coarse-grain simulations in the context of functional dynamics and structural plasticity of GPCRs. We envision that this comprehensive overview will help resolve differences in computational studies and provide a way forward.

Visualization of local Ca2+ dynamics with genetically encoded bioluminescent reporters.

PubMed

Rogers, Kelly L; Stinnakre, Jacques; Agulhon, Cendra; Jublot, Delphine; Shorte, Spencer L; Kremer, Eric J; Brûlet, Philippe

2005-02-01

Measurements of local Ca2+ signalling at different developmental stages and/or in specific cell types is important for understanding aspects of brain functioning. The use of light excitation in fluorescence imaging can cause phototoxicity, photobleaching and auto-fluorescence. In contrast, bioluminescence does not require the input of radiative energy and can therefore be measured over long periods, with very high temporal resolution. Aequorin is a genetically encoded Ca(2+)-sensitive bioluminescent protein, however, its low quantum yield prevents dynamic measurements of Ca2+ responses in single cells. To overcome this limitation, we recently reported the bi-functional Ca2+ reporter gene, GFP-aequorin (GA), which was developed specifically to improve the light output and stability of aequorin chimeras [V. Baubet, et al., (2000) PNAS, 97, 7260-7265]. In the current study, we have genetically targeted GA to different microdomains important in synaptic transmission, including to the mitochondrial matrix, endoplasmic reticulum, synaptic vesicles and to the postsynaptic density. We demonstrate that these reporters enable 'real-time' measurements of subcellular Ca2+ changes in single mammalian neurons using bioluminescence. The high signal-to-noise ratio of these reporters is also important in that it affords the visualization of Ca2+ dynamics in cell-cell communication in neuronal cultures and tissue slices. Further, we demonstrate the utility of this approach in ex-vivo preparations of mammalian retina, a paradigm in which external light input should be controlled. This represents a novel molecular imaging approach for non-invasive monitoring of local Ca2+ dynamics and cellular communication in tissue or whole animal studies.

Visual acuity and quality of life in dry eye disease: Proceedings of the OCEAN group meeting.

PubMed

Benítez-Del-Castillo, José; Labetoulle, Marc; Baudouin, Christophe; Rolando, Maurizio; Akova, Yonca A; Aragona, Pasquale; Geerling, Gerd; Merayo-Lloves, Jesús; Messmer, Elisabeth M; Boboridis, Kostas

2017-04-01

Dry eye disease (DED) results in tear film instability and hyperosmolarity, inflammation of the ocular surface and, ultimately, visual disturbance that can significantly impact a patient's quality of life. The effects on visual acuity result in difficulties with driving, reading and computer use and negatively impact psychological health. These effects also extend to the workplace, with a loss of productivity and quality of work causing substantial economic losses. The effects of DED and the impact on vision experienced by patients may not be given sufficient importance by ophthalmologists. Functional visual acuity (FVA) is a measure of visual acuity after sustained eye opening without blinking for at least 10 s and mimics the sustained visual acuity of daily life. Measuring dynamic FVA allows the detection of impaired visual function in patients with DED who may display normal conventional visual acuity. There are currently several tests and methods that can be used to measure dynamic visual function: the SSC-350 FVA measurement system, assessment of best-corrected visual acuity decay using the interblink visual acuity decay test, serial measurements of ocular and corneal higher order aberrations, and measurement of dynamic vision quality using the Optical Quality Analysis System. Although the equipment for these methods may be too large or unaffordable for use in clinical practice, FVA testing is an important assessment for DED. Copyright © 2016 Elsevier Inc. All rights reserved.

Emotion unfolded by motion: a role for parietal lobe in decoding dynamic facial expressions.

PubMed

Sarkheil, Pegah; Goebel, Rainer; Schneider, Frank; Mathiak, Klaus

2013-12-01

Facial expressions convey important emotional and social information and are frequently applied in investigations of human affective processing. Dynamic faces may provide higher ecological validity to examine perceptual and cognitive processing of facial expressions. Higher order processing of emotional faces was addressed by varying the task and virtual face models systematically. Blood oxygenation level-dependent activation was assessed using functional magnetic resonance imaging in 20 healthy volunteers while viewing and evaluating either emotion or gender intensity of dynamic face stimuli. A general linear model analysis revealed that high valence activated a network of motion-responsive areas, indicating that visual motion areas support perceptual coding for the motion-based intensity of facial expressions. The comparison of emotion with gender discrimination task revealed increased activation of inferior parietal lobule, which highlights the involvement of parietal areas in processing of high level features of faces. Dynamic emotional stimuli may help to emphasize functions of the hypothesized 'extended' over the 'core' system for face processing.

Reaction-based small-molecule fluorescent probes for dynamic detection of ROS and transient redox changes in living cells and small animals.

PubMed

Lü, Rui

2017-09-01

Dynamic detection of transient redox changes in living cells and animals has broad implications for human health and disease diagnosis, because intracellular redox homeostasis regulated by reactive oxygen species (ROS) plays important role in cell functions, normal physiological functions and some serious human diseases (e.g., cancer, Alzheimer's disease, diabetes, etc.) usually have close relationship with the intracellular redox status. Small-molecule ROS-responsive fluorescent probes can act as powerful tools for dynamic detection of ROS and redox changes in living cells and animals through fluorescence imaging techniques; and great advances have been achieved recently in the design and synthesis of small-molecule ROS-responsive fluorescent probes. This article highlights up-to-date achievements in designing and using the reaction-based small-molecule fluorescent probes (with high sensitivity and selectivity to ROS and redox cycles) in the dynamic detection of ROS and transient redox changes in living cells and animals through fluorescence imaging. Copyright © 2017. Published by Elsevier Ltd.

Real-time observation of the conformational dynamics of mitochondrial Hsp70 by spFRET

PubMed Central

Sikor, Martin; Mapa, Koyeli; von Voithenberg, Lena Voith; Mokranjac, Dejana; Lamb, Don C

2013-01-01

The numerous functions of the important class of molecular chaperones, heat shock proteins 70 (Hsp70), rely on cycles of intricate conformational changes driven by ATP-hydrolysis and regulated by cochaperones and substrates. Here, we used Förster resonance energy transfer to study the conformational dynamics of individual molecules of Ssc1, a mitochondrial Hsp70, in real time. The intrinsic dynamics of the substrate-binding domain of Ssc1 was observed to be uncoupled from the dynamic interactions between substrate- and nucleotide-binding domains. Analysis of the fluctuations in the interdomain separation revealed frequent transitions to a nucleotide-free state. The nucleotide-exchange factor Mge1 did not induce ADP release, as expected, but rather facilitated binding of ATP. These results indicate that the conformational cycle of Ssc1 is more elaborate than previously thought and provide insight into how the Hsp70s can perform a wide variety of functions. PMID:23624933

FATE-HD: A spatially and temporally explicit integrated model for predicting vegetation structure and diversity at regional scale

PubMed Central

Isabelle, Boulangeat; Damien, Georges; Wilfried, Thuiller

2014-01-01

During the last decade, despite strenuous efforts to develop new models and compare different approaches, few conclusions have been drawn on their ability to provide robust biodiversity projections in an environmental change context. The recurring suggestions are that models should explicitly (i) include spatiotemporal dynamics; (ii) consider multiple species in interactions; and (iii) account for the processes shaping biodiversity distribution. This paper presents a biodiversity model (FATE-HD) that meets this challenge at regional scale by combining phenomenological and process-based approaches and using well-defined plant functional groups. FATE-HD has been tested and validated in a French National Park, demonstrating its ability to simulate vegetation dynamics, structure and diversity in response to disturbances and climate change. The analysis demonstrated the importance of considering biotic interactions, spatio-temporal dynamics, and disturbances in addition to abiotic drivers to simulate vegetation dynamics. The distribution of pioneer trees was particularly improved, as were all undergrowth functional groups. PMID:24214499

Impact of Plant Functional Types on Coherence Between Precipitation and Soil Moisture: A Wavelet Analysis

NASA Astrophysics Data System (ADS)

Liu, Qi; Hao, Yonghong; Stebler, Elaine; Tanaka, Nobuaki; Zou, Chris B.

2017-12-01

Mapping the spatiotemporal patterns of soil moisture within heterogeneous landscapes is important for resource management and for the understanding of hydrological processes. A critical challenge in this mapping is comparing remotely sensed or in situ observations from areas with different vegetation cover but subject to the same precipitation regime. We address this challenge by wavelet analysis of multiyear observations of soil moisture profiles from adjacent areas with contrasting plant functional types (grassland, woodland, and encroached) and precipitation. The analysis reveals the differing soil moisture patterns and dynamics between plant functional types. The coherence at high-frequency periodicities between precipitation and soil moisture generally decreases with depth but this is much more pronounced under woodland compared to grassland. Wavelet analysis provides new insights on soil moisture dynamics across plant functional types and is useful for assessing differences and similarities in landscapes with heterogeneous vegetation cover.

Nonparametric variational optimization of reaction coordinates

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

Banushkina, Polina V.; Krivov, Sergei V., E-mail: s.krivov@leeds.ac.uk

State of the art realistic simulations of complex atomic processes commonly produce trajectories of large size, making the development of automated analysis tools very important. A popular approach aimed at extracting dynamical information consists of projecting these trajectories into optimally selected reaction coordinates or collective variables. For equilibrium dynamics between any two boundary states, the committor function also known as the folding probability in protein folding studies is often considered as the optimal coordinate. To determine it, one selects a functional form with many parameters and trains it on the trajectories using various criteria. A major problem with such anmore » approach is that a poor initial choice of the functional form may lead to sub-optimal results. Here, we describe an approach which allows one to optimize the reaction coordinate without selecting its functional form and thus avoiding this source of error.« less

Systematic methods for defining coarse-grained maps in large biomolecules.

PubMed

Zhang, Zhiyong

2015-01-01

Large biomolecules are involved in many important biological processes. It would be difficult to use large-scale atomistic molecular dynamics (MD) simulations to study the functional motions of these systems because of the computational expense. Therefore various coarse-grained (CG) approaches have attracted rapidly growing interest, which enable simulations of large biomolecules over longer effective timescales than all-atom MD simulations. The first issue in CG modeling is to construct CG maps from atomic structures. In this chapter, we review the recent development of a novel and systematic method for constructing CG representations of arbitrarily complex biomolecules, in order to preserve large-scale and functionally relevant essential dynamics (ED) at the CG level. In this ED-CG scheme, the essential dynamics can be characterized by principal component analysis (PCA) on a structural ensemble, or elastic network model (ENM) of a single atomic structure. Validation and applications of the method cover various biological systems, such as multi-domain proteins, protein complexes, and even biomolecular machines. The results demonstrate that the ED-CG method may serve as a very useful tool for identifying functional dynamics of large biomolecules at the CG level.

Actin Interacting Protein1 and Actin Depolymerizing Factor Drive Rapid Actin Dynamics in Physcomitrella patens[W

PubMed Central

Augustine, Robert C.; Pattavina, Kelli A.; Tüzel, Erkan; Vidali, Luis; Bezanilla, Magdalena

2011-01-01

The remodeling of actin networks is required for a variety of cellular processes in eukaryotes. In plants, several actin binding proteins have been implicated in remodeling cortical actin filaments (F-actin). However, the extent to which these proteins support F-actin dynamics in planta has not been tested. Using reverse genetics, complementation analyses, and cell biological approaches, we assessed the in vivo function of two actin turnover proteins: actin interacting protein1 (AIP1) and actin depolymerizing factor (ADF). We report that AIP1 is a single-copy gene in the moss Physcomitrella patens. AIP1 knockout plants are viable but have reduced expansion of tip-growing cells. AIP1 is diffusely cytosolic and functions in a common genetic pathway with ADF to promote tip growth. Specifically, ADF can partially compensate for loss of AIP1, and AIP1 requires ADF for function. Consistent with a role in actin remodeling, AIP1 knockout lines accumulate F-actin bundles, have fewer dynamic ends, and have reduced severing frequency. Importantly, we demonstrate that AIP1 promotes and ADF is essential for cortical F-actin dynamics. PMID:22003077

CCR5 RNA Pseudoknots: Residue and Site-Specific Labeling correlate Internal Motions with microRNA Binding.

PubMed

Chen, Bin; Longhini, Andrew P; Nußbaumer, Felix; Kreutz, Christoph; Dinman, Jonathan D; Dayie, T Kwaku

2018-04-11

Conformational dynamics of RNA molecules play a critical role in governing their biological functions. Measurements of RNA dynamic behavior sheds important light on sites that interact with their binding partners or cellular stimulators. However, such measurements using solution-state NMR are difficult for large RNA molecules (>70 nt; nt=nucleotides) owing to severe spectral overlap, homonuclear 13 C scalar couplings, and line broadening. Herein, a strategic combination of solid-phase synthesis, site-specific isotopic labeled phosphoramidites, and enzymatic ligation is introduced. This approach allowed the position-specific insertion of isotopic probes into a 96 nt CCR5 RNA fragment. Accurate measurements of functional dynamics using the Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion (RD) experiments enabled extraction of the exchange rates and populations of this RNA. NMR chemical shift perturbation analysis of the RNA/microRNA-1224 complex indicated that A90-C1' of the pseudoknot exhibits similar changes in chemical shift observed in the excited state. This work demonstrates the general applicability of a NMR-labeling strategy to probe functional RNA structural dynamics. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Differential Dynamic Engagement within 24 SH3 Domain: Peptide Complexes Revealed by Co-Linear Chemical Shift Perturbation Analysis

PubMed Central

Stollar, Elliott J.; Lin, Hong; Davidson, Alan R.; Forman-Kay, Julie D.

2012-01-01

There is increasing evidence for the functional importance of multiple dynamically populated states within single proteins. However, peptide binding by protein-protein interaction domains, such as the SH3 domain, has generally been considered to involve the full engagement of peptide to the binding surface with minimal dynamics and simple methods to determine dynamics at the binding surface for multiple related complexes have not been described. We have used NMR spectroscopy combined with isothermal titration calorimetry to comprehensively examine the extent of engagement to the yeast Abp1p SH3 domain for 24 different peptides. Over one quarter of the domain residues display co-linear chemical shift perturbation (CCSP) behavior, in which the position of a given chemical shift in a complex is co-linear with the same chemical shift in the other complexes, providing evidence that each complex exists as a unique dynamic rapidly inter-converting ensemble. The extent the specificity determining sub-surface of AbpSH3 is engaged as judged by CCSP analysis correlates with structural and thermodynamic measurements as well as with functional data, revealing the basis for significant structural and functional diversity amongst the related complexes. Thus, CCSP analysis can distinguish peptide complexes that may appear identical in terms of general structure and percent peptide occupancy but have significant local binding differences across the interface, affecting their ability to transmit conformational change across the domain and resulting in functional differences. PMID:23251481

Protein-Protein Interactions of Azurin Complex by Coarse-Grained Simulations with a Gō-Like Model

NASA Astrophysics Data System (ADS)

Rusmerryani, Micke; Takasu, Masako; Kawaguchi, Kazutomo; Saito, Hiroaki; Nagao, Hidemi

Proteins usually perform their biological functions by forming a complex with other proteins. It is very important to study the protein-protein interactions since these interactions are crucial in many processes of a living organism. In this study, we develop a coarse grained model to simulate protein complex in liquid system. We carry out molecular dynamics simulations with topology-based potential interactions to simulate dynamical properties of Pseudomonas Aeruginosa azurin complex systems. Azurin is known to play an essential role as an anticancer agent and bind many important intracellular molecules. Some physical properties are monitored during simulation time to get a better understanding of the influence of protein-protein interactions to the azurin complex dynamics. These studies will provide valuable insights for further investigation on protein-protein interactions in more realistic system.

Optimizing Natural Gas Networks through Dynamic Manifold Theory and a Decentralized Algorithm: Belgium Case Study

NASA Astrophysics Data System (ADS)

Koch, Caleb; Winfrey, Leigh

2014-10-01

Natural Gas is a major energy source in Europe, yet political instabilities have the potential to disrupt access and supply. Energy resilience is an increasingly essential construct and begins with transmission network design. This study proposes a new way of thinking about modelling natural gas flow. Rather than relying on classical economic models, this problem is cast into a time-dependent Hamiltonian dynamics discussion. Traditional Natural Gas constraints, including inelastic demand and maximum/minimum pipe flows, are portrayed as energy functions and built into the dynamics of each pipe flow. Doing so allows the constraints to be built into the dynamics of each pipeline. As time progresses in the model, natural gas flow rates find the minimum energy, thus the optimal gas flow rates. The most important result of this study is using dynamical principles to ensure the output of natural gas at demand nodes remains constant, which is important for country to country natural gas transmission. Another important step in this study is building the dynamics of each flow in a decentralized algorithm format. Decentralized regulation has solved congestion problems for internet data flow, traffic flow, epidemiology, and as demonstrated in this study can solve the problem of Natural Gas congestion. A mathematical description is provided for how decentralized regulation leads to globally optimized network flow. Furthermore, the dynamical principles and decentralized algorithm are applied to a case study of the Fluxys Belgium Natural Gas Network.

Dynamical network of residue–residue contacts reveals coupled allosteric effects in recognition, catalysis, and mutation

PubMed Central

Doshi, Urmi; Holliday, Michael J.; Eisenmesser, Elan Z.; Hamelberg, Donald

2016-01-01

Detailed understanding of how conformational dynamics orchestrates function in allosteric regulation of recognition and catalysis remains ambiguous. Here, we simulate CypA using multiple-microsecond-long atomistic molecular dynamics in explicit solvent and carry out NMR experiments. We analyze a large amount of time-dependent multidimensional data with a coarse-grained approach and map key dynamical features within individual macrostates by defining dynamics in terms of residue–residue contacts. The effects of substrate binding are observed to be largely sensed at a location over 15 Å from the active site, implying its importance in allostery. Using NMR experiments, we confirm that a dynamic cluster of residues in this distal region is directly coupled to the active site. Furthermore, the dynamical network of interresidue contacts is found to be coupled and temporally dispersed, ranging over 4 to 5 orders of magnitude. Finally, using network centrality measures we demonstrate the changes in the communication network, connectivity, and influence of CypA residues upon substrate binding, mutation, and during catalysis. We identify key residues that potentially act as a bottleneck in the communication flow through the distinct regions in CypA and, therefore, as targets for future mutational studies. Mapping these dynamical features and the coupling of dynamics to function has crucial ramifications in understanding allosteric regulation in enzymes and proteins, in general. PMID:27071107

Dynamical systems, attractors, and neural circuits.

PubMed

Miller, Paul

2016-01-01

Biology is the study of dynamical systems. Yet most of us working in biology have limited pedagogical training in the theory of dynamical systems, an unfortunate historical fact that can be remedied for future generations of life scientists. In my particular field of systems neuroscience, neural circuits are rife with nonlinearities at all levels of description, rendering simple methodologies and our own intuition unreliable. Therefore, our ideas are likely to be wrong unless informed by good models. These models should be based on the mathematical theories of dynamical systems since functioning neurons are dynamic-they change their membrane potential and firing rates with time. Thus, selecting the appropriate type of dynamical system upon which to base a model is an important first step in the modeling process. This step all too easily goes awry, in part because there are many frameworks to choose from, in part because the sparsely sampled data can be consistent with a variety of dynamical processes, and in part because each modeler has a preferred modeling approach that is difficult to move away from. This brief review summarizes some of the main dynamical paradigms that can arise in neural circuits, with comments on what they can achieve computationally and what signatures might reveal their presence within empirical data. I provide examples of different dynamical systems using simple circuits of two or three cells, emphasizing that any one connectivity pattern is compatible with multiple, diverse functions.

Nonlinear dynamics, fractals, cardiac physiology and sudden death

NASA Technical Reports Server (NTRS)

Goldberger, Ary L.

1987-01-01

The authors propose a diametrically opposite viewpoint to the generally accepted tendency of equating healthy function with order and disease with chaos. With regard to the question of sudden cardiac death and chaos, it is suggested that certain features of dynamical chaos related to fractal structure and fractal dynamics may be important organizing principles in normal physiology and that certain pathologies, including ventricular fibrillation, represent a class of 'pathological periodicities'. Some laboratory work bearing on the relation of nonlinear analysis to physiological and pathophysiological data is briefly reviewed, with tentative theories and models described in reference to the mechanism of ventricular fibrillation.

Oceanic biogeochemical controls on global dynamics of persistent organic pollutants.

PubMed

Dachs, Jordi; Lohmann, Rainer; Ockenden, Wendy A; Méjanelle, Laurence; Eisenreich, Steven J; Jones, Kevin C

2002-10-15

Understanding and quantifying the global dynamics and sinks of persistent organic pollutants (POPs) is important to assess their environmental impact and fate. Air-surface exchange processes, where temperature plays a central role in controlling volatilization and deposition, are of key importance in controlling global POP dynamics. The present study is an assessment of the role of oceanic biogeochemical processes, notably phytoplankton uptake and vertical fluxes of particles, on the global dynamics of POPs. Field measurements of atmospheric polychlorinated biphenyls (PCBs), polychlorinated dibenzodioxins (PCDDs), and furans (PCDFs) are combined with remote sensing estimations of oceanic temperature, wind speed, and chlorophyll, to model the interactions between air-water exchange, phytoplankton uptake, and export of organic matter and POPs out of the mixed surface ocean layer. Deposition is enhanced in the mid-high latitudes and is driven by sinking marine particulate matter, rather than by a cold condensation effect. However, the relative contribution of the biological pump is a function of the physical-chemical properties of POPs. It is concluded that oceanic biogeochemical processes play a critical role in controlling the global dynamics and the ultimate sink of POPs.

Joint nonlinearity effects in the design of a flexible truss structure control system

NASA Technical Reports Server (NTRS)

Mercadal, Mathieu

1986-01-01

Nonlinear effects are introduced in the dynamics of large space truss structures by the connecting joints which are designed with rather important tolerances to facilitate the assembly of the structures in space. The purpose was to develop means to investigate the nonlinear dynamics of the structures, particularly the limit cycles that might occur when active control is applied to the structures. An analytical method was sought and derived to predict the occurrence of limit cycles and to determine their stability. This method is mainly based on the quasi-linearization of every joint using describing functions. This approach was proven successful when simple dynamical systems were tested. Its applicability to larger systems depends on the amount of computations it requires, and estimates of the computational task tend to indicate that the number of individual sources of nonlinearity should be limited. Alternate analytical approaches, which do not account for every single nonlinearity, or the simulation of a simplified model of the dynamical system should, therefore, be investigated to determine a more effective way to predict limit cycles in large dynamical systems with an important number of distributed nonlinearities.

Dynamic of Air Invasion in an Immersed Granular Layer

NASA Astrophysics Data System (ADS)

Varas, G.; Ramos, G.; Géminard, J. C.; Vidal, V.

2014-12-01

Displacement processes (typically, grains displaced by a fluid) are the driving mechanism which control the dynamics of many geological processes (e.g. oil extraction, air sparging, piercement structures). They also play an important role in a wide range of industrial applications, from ground water hydrology and soil mechanics to agricultural engineering. The interaction between one or more moving fluids (e.g. rising gas immersed in a granular medium) and grains control the dynamics of these phenomena. Due to their economic and ecological importance, it is essential to understand the variety and potentiality of these phenomena. When an ascending air passes trough an immersed granular bed its fluidized producing the grains to start to move. When this process is repeated, its created a fluidized zone that evolves over time. Here, we investigate the morphology and dynamics of the region invaded by air as a function of a dimensionless parameter χ which accounts for the relative effects of the gravity and the capillarity. We propose new experimental observations on the air invasion regimes and on the morphology of the fluidized zone, in particular its growth dynamics.

Weakly bound water structure, bond valence saturation and water dynamics at the goethite (100) surface/aqueous interface: ab initio dynamical simulations

DOE PAGES

Chen, Ying; Bylaska, Eric J.; Weare, John H.

2017-03-31

Many important geochemical and biogeochemical reactions occur in the mineral/formation water interface of the highly abundant mineral, goethite (α-Fe(OOH). Ab-initio molecular dynamics (AIMD) simulations of the goethite α-FeOOH (100) surface and the structure, water bond formation and dynamics of water molecules in the mineral/aqueous interface are presented. Here, several exchange correlation functionals were employed (PBE96, PBE96+Grimme, and PBE0) in the simulations of a (3 x 2) goethite surface with 65 absorbed water molecules in a 3D-periodic supercell (a=30 Å, FeOOH slab ~12 Å thick, solvation layer ~18 Å thick).

Weakly bound water structure, bond valence saturation and water dynamics at the goethite (100) surface/aqueous interface: ab initio dynamical simulations

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

Chen, Ying; Bylaska, Eric J.; Weare, John H.

Many important geochemical and biogeochemical reactions occur in the mineral/formation water interface of the highly abundant mineral, goethite (α-Fe(OOH). Ab-initio molecular dynamics (AIMD) simulations of the goethite α-FeOOH (100) surface and the structure, water bond formation and dynamics of water molecules in the mineral/aqueous interface are presented. Here, several exchange correlation functionals were employed (PBE96, PBE96+Grimme, and PBE0) in the simulations of a (3 x 2) goethite surface with 65 absorbed water molecules in a 3D-periodic supercell (a=30 Å, FeOOH slab ~12 Å thick, solvation layer ~18 Å thick).

Cyclic and Linear Monoterpenes in Phospholipid Membranes: Phase Behavior, Bilayer Structure, and Molecular Dynamics.

PubMed

Pham, Quoc Dat; Topgaard, Daniel; Sparr, Emma

2015-10-13

Monoterpenes are abundant in essential oils extracted from plants. These relatively small and hydrophobic molecules have shown important biological functions, including antimicrobial activity and membrane penetration enhancement. The interaction between the monoterpenes and lipid bilayers is considered important to the understanding of the biological functions of monoterpenes. In this study, we investigated the effect of cyclic and linear monoterpenes on the structure and dynamics of lipids in model membranes. We have studied the ternary system 1,2-dimyristoyl-sn-glycero-3-phosphocholine-monoterpene-water as a model with a focus on dehydrated conditions. By combining complementary techniques, including differential scanning calorimetry, solid-state nuclear magnetic resonance, and small- and wide-angle X-ray scattering, bilayer structure, phase transitions, and lipid molecular dynamics were investigated at different water contents. Monoterpenes cause pronounced melting point depression and phase segregation in lipid bilayers, and the extent of these effects depends on the hydration conditions. The addition of a small amount of thymol to the fluid bilayer (volume fraction of 0.03 in the bilayer) leads to an increased order in the acyl chain close to the bilayer interface. The findings are discussed in relation to biological systems and lipid formulations.

Nematode grazing promotes bacterial community dynamics in soil at the aggregate level

PubMed Central

Jiang, Yuji; Liu, Manqiang; Zhang, Jiabao; Chen, Yan; Chen, Xiaoyun; Chen, Lijun; Li, Huixin; Zhang, Xue-Xian; Sun, Bo

2017-01-01

Nematode predation has important roles in determining bacterial community composition and dynamics, but the extent of the effects remains largely rudimentary, particularly in natural environment settings. Here, we investigated the complex microbial–microfaunal interactions in the rhizosphere of maize grown in red soils, which were derived from four long-term fertilization regimes. Root-free rhizosphere soil samples were separated into three aggregate fractions whereby the abundance and community composition were examined for nematode and total bacterial communities. A functional group of alkaline phosphomonoesterase (ALP) producing bacteria was included to test the hypothesis that nematode grazing may significantly affect specific bacteria-mediated ecological functions, that is, organic phosphate cycling in soil. Results of correlation analysis, structural equation modeling and interaction networks combined with laboratory microcosm experiments consistently indicated that bacterivorous nematodes enhanced bacterial diversity, and the abundance of bacterivores was positively correlated with bacterial biomass, including ALP-producing bacterial abundance. Significantly, such effects were more pronounced in large macroaggregates than in microaggregates. There was a positive correlation between the most dominant bacterivores Protorhabditis and the ALP-producing keystone 'species' Mesorhizobium. Taken together, these findings implicate important roles of nematodes in stimulating bacterial dynamics in a spatially dependent manner. PMID:28742069

Nematode grazing promotes bacterial community dynamics in soil at the aggregate level.

PubMed

Jiang, Yuji; Liu, Manqiang; Zhang, Jiabao; Chen, Yan; Chen, Xiaoyun; Chen, Lijun; Li, Huixin; Zhang, Xue-Xian; Sun, Bo

2017-12-01

Nematode predation has important roles in determining bacterial community composition and dynamics, but the extent of the effects remains largely rudimentary, particularly in natural environment settings. Here, we investigated the complex microbial-microfaunal interactions in the rhizosphere of maize grown in red soils, which were derived from four long-term fertilization regimes. Root-free rhizosphere soil samples were separated into three aggregate fractions whereby the abundance and community composition were examined for nematode and total bacterial communities. A functional group of alkaline phosphomonoesterase (ALP) producing bacteria was included to test the hypothesis that nematode grazing may significantly affect specific bacteria-mediated ecological functions, that is, organic phosphate cycling in soil. Results of correlation analysis, structural equation modeling and interaction networks combined with laboratory microcosm experiments consistently indicated that bacterivorous nematodes enhanced bacterial diversity, and the abundance of bacterivores was positively correlated with bacterial biomass, including ALP-producing bacterial abundance. Significantly, such effects were more pronounced in large macroaggregates than in microaggregates. There was a positive correlation between the most dominant bacterivores Protorhabditis and the ALP-producing keystone 'species' Mesorhizobium. Taken together, these findings implicate important roles of nematodes in stimulating bacterial dynamics in a spatially dependent manner.

Probabilistic assessment of dynamic system performance. Part 3

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

Belhadj, Mohamed

1993-01-01

Accurate prediction of dynamic system failure behavior can be important for the reliability and risk analyses of nuclear power plants, as well as for their backfitting to satisfy given constraints on overall system reliability, or optimization of system performance. Global analysis of dynamic systems through investigating the variations in the structure of the attractors of the system and the domains of attraction of these attractors as a function of the system parameters is also important for nuclear technology in order to understand the fault-tolerance as well as the safety margins of the system under consideration and to insure a safemore » operation of nuclear reactors. Such a global analysis would be particularly relevant to future reactors with inherent or passive safety features that are expected to rely on natural phenomena rather than active components to achieve and maintain safe shutdown. Conventionally, failure and global analysis of dynamic systems necessitate the utilization of different methodologies which have computational limitations on the system size that can be handled. Using a Chapman-Kolmogorov interpretation of system dynamics, a theoretical basis is developed that unifies these methodologies as special cases and which can be used for a comprehensive safety and reliability analysis of dynamic systems.« less

Machine Learning and Network Analysis of Molecular Dynamics Trajectories Reveal Two Chains of Red/Ox-specific Residue Interactions in Human Protein Disulfide Isomerase.

PubMed

Karamzadeh, Razieh; Karimi-Jafari, Mohammad Hossein; Sharifi-Zarchi, Ali; Chitsaz, Hamidreza; Salekdeh, Ghasem Hosseini; Moosavi-Movahedi, Ali Akbar

2017-06-16

The human protein disulfide isomerase (hPDI), is an essential four-domain multifunctional enzyme. As a result of disulfide shuffling in its terminal domains, hPDI exists in two oxidation states with different conformational preferences which are important for substrate binding and functional activities. Here, we address the redox-dependent conformational dynamics of hPDI through molecular dynamics (MD) simulations. Collective domain motions are identified by the principal component analysis of MD trajectories and redox-dependent opening-closing structure variations are highlighted on projected free energy landscapes. Then, important structural features that exhibit considerable differences in dynamics of redox states are extracted by statistical machine learning methods. Mapping the structural variations to time series of residue interaction networks also provides a holistic representation of the dynamical redox differences. With emphasizing on persistent long-lasting interactions, an approach is proposed that compiled these time series networks to a single dynamic residue interaction network (DRIN). Differential comparison of DRIN in oxidized and reduced states reveals chains of residue interactions that represent potential allosteric paths between catalytic and ligand binding sites of hPDI.

Protonation States in molecular dynamics simulations of peptide folding and binding.

PubMed

Ben-Shimon, Avraham; Shalev, Deborah E; Niv, Masha Y

2013-01-01

Peptides are important signaling modules, acting both as individual hormones and as parts of larger molecules, mediating their protein-protein interactions. Many peptidic and peptidomimetic drugs have reached the marketplace and opportunities for peptide-based drug discovery are on the rise. pH-dependent behavior of peptides is well documented in the context of misfolding diseases and peptide translocation. Changes in the protonation states of peptide residues often have a crucial effect on a peptide's structure, dynamics and function, which may be exploited for biotechnological applications. The current review surveys the increasing levels of sophistication in the treatment of protonation states in computational studies involving peptides. Specifically we describe I) the common practice of assigning a single protonation state and using it throughout the dynamic simulation, II) approaches that consider multiple protonation states and compare computed observables to experimental ones, III) constant pH molecular dynamics methods that couple changes in protonation states with conformational dynamics "on the fly". Applications of conformational dynamics treatment of peptides in the context of binding, folding and interactions with the membrane are presented, illustrating the growing body of work in this field and highlighting the importance of careful handling of protonation states of peptidic residues.

Control of complex networks requires both structure and dynamics

NASA Astrophysics Data System (ADS)

Gates, Alexander J.; Rocha, Luis M.

2016-04-01

The study of network structure has uncovered signatures of the organization of complex systems. However, there is also a need to understand how to control them; for example, identifying strategies to revert a diseased cell to a healthy state, or a mature cell to a pluripotent state. Two recent methodologies suggest that the controllability of complex systems can be predicted solely from the graph of interactions between variables, without considering their dynamics: structural controllability and minimum dominating sets. We demonstrate that such structure-only methods fail to characterize controllability when dynamics are introduced. We study Boolean network ensembles of network motifs as well as three models of biochemical regulation: the segment polarity network in Drosophila melanogaster, the cell cycle of budding yeast Saccharomyces cerevisiae, and the floral organ arrangement in Arabidopsis thaliana. We demonstrate that structure-only methods both undershoot and overshoot the number and which sets of critical variables best control the dynamics of these models, highlighting the importance of the actual system dynamics in determining control. Our analysis further shows that the logic of automata transition functions, namely how canalizing they are, plays an important role in the extent to which structure predicts dynamics.

Dynamics of a neural system with a multiscale architecture

PubMed Central

Breakspear, Michael; Stam, Cornelis J

2005-01-01

The architecture of the brain is characterized by a modular organization repeated across a hierarchy of spatial scales—neurons, minicolumns, cortical columns, functional brain regions, and so on. It is important to consider that the processes governing neural dynamics at any given scale are not only determined by the behaviour of other neural structures at that scale, but also by the emergent behaviour of smaller scales, and the constraining influence of activity at larger scales. In this paper, we introduce a theoretical framework for neural systems in which the dynamics are nested within a multiscale architecture. In essence, the dynamics at each scale are determined by a coupled ensemble of nonlinear oscillators, which embody the principle scale-specific neurobiological processes. The dynamics at larger scales are ‘slaved’ to the emergent behaviour of smaller scales through a coupling function that depends on a multiscale wavelet decomposition. The approach is first explicated mathematically. Numerical examples are then given to illustrate phenomena such as between-scale bifurcations, and how synchronization in small-scale structures influences the dynamics in larger structures in an intuitive manner that cannot be captured by existing modelling approaches. A framework for relating the dynamical behaviour of the system to measured observables is presented and further extensions to capture wave phenomena and mode coupling are suggested. PMID:16087448

Dynamics and control of the ERK signaling pathway: Sensitivity, bistability, and oscillations.

PubMed

Arkun, Yaman; Yasemi, Mohammadreza

2018-01-01

Cell signaling is the process by which extracellular information is transmitted into the cell to perform useful biological functions. The ERK (extracellular-signal-regulated kinase) signaling controls several cellular processes such as cell growth, proliferation, differentiation and apoptosis. The ERK signaling pathway considered in this work starts with an extracellular stimulus and ends with activated (double phosphorylated) ERK which gets translocated into the nucleus. We model and analyze this complex pathway by decomposing it into three functional subsystems. The first subsystem spans the initial part of the pathway from the extracellular growth factor to the formation of the SOS complex, ShC-Grb2-SOS. The second subsystem includes the activation of Ras which is mediated by the SOS complex. This is followed by the MAPK subsystem (or the Raf-MEK-ERK pathway) which produces the double phosphorylated ERK upon being activated by Ras. Although separate models exist in the literature at the subsystems level, a comprehensive model for the complete system including the important regulatory feedback loops is missing. Our dynamic model combines the existing subsystem models and studies their steady-state and dynamic interactions under feedback. We establish conditions under which bistability and oscillations exist for this important pathway. In particular, we show how the negative and positive feedback loops affect the dynamic characteristics that determine the cellular outcome.

Optical Tweezers-Based Measurements of Forces and Dynamics at Microtubule Ends.

PubMed

Baclayon, Marian; Kalisch, Svenja-Marei; Hendel, Ed; Laan, Liedewij; Husson, Julien; Munteanu, E Laura; Dogterom, Marileen

2017-01-01

Microtubules are dynamic cytoskeletal polymers that polymerize and depolymerize while interacting with different proteins and structures within the cell. The highly regulated dynamic properties as well as the pushing and pulling forces generated by dynamic microtubule ends play important roles in processes such as in cell division. For instance, microtubule end-binding proteins are known to affect dramatically the dynamic properties of microtubules, and cortical dyneins are known to mediate pulling forces on microtubule ends. We discuss in this chapter our efforts to reconstitute these systems in vitro and mimic their interactions with structures within the cell using micro-fabricated barriers. Using an optical tweezers setup, we investigate the dynamics and forces of microtubules growing against functionalized barriers in the absence and presence of end-binding proteins and barrier-attached motor proteins. This setup allows high-speed as well as nanometer and piconewton resolution measurements on dynamic microtubules.

3D Protein Dynamics in the Cell Nucleus.

PubMed

Singh, Anand P; Galland, Rémi; Finch-Edmondson, Megan L; Grenci, Gianluca; Sibarita, Jean-Baptiste; Studer, Vincent; Viasnoff, Virgile; Saunders, Timothy E

2017-01-10

The three-dimensional (3D) architecture of the cell nucleus plays an important role in protein dynamics and in regulating gene expression. However, protein dynamics within the 3D nucleus are poorly understood. Here, we present, to our knowledge, a novel combination of 1) single-objective based light-sheet microscopy, 2) photoconvertible proteins, and 3) fluorescence correlation microscopy, to quantitatively measure 3D protein dynamics in the nucleus. We are able to acquire >3400 autocorrelation functions at multiple spatial positions within a nucleus, without significant photobleaching, allowing us to make reliable estimates of diffusion dynamics. Using this tool, we demonstrate spatial heterogeneity in Polymerase II dynamics in live U2OS cells. Further, we provide detailed measurements of human-Yes-associated protein diffusion dynamics in a human gastric cancer epithelial cell line. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Formation mechanism of a basin of attraction for passive dynamic walking induced by intrinsic hyperbolicity

PubMed Central

Aoi, Shinya; Tsuchiya, Kazuo; Kokubu, Hiroshi

2016-01-01

Passive dynamic walking is a useful model for investigating the mechanical functions of the body that produce energy-efficient walking. The basin of attraction is very small and thin, and it has a fractal-like shape; this explains the difficulty in producing stable passive dynamic walking. The underlying mechanism that produces these geometric characteristics was not known. In this paper, we consider this from the viewpoint of dynamical systems theory, and we use the simplest walking model to clarify the mechanism that forms the basin of attraction for passive dynamic walking. We show that the intrinsic saddle-type hyperbolicity of the upright equilibrium point in the governing dynamics plays an important role in the geometrical characteristics of the basin of attraction; this contributes to our understanding of the stability mechanism of bipedal walking. PMID:27436971

Multimodal Classification of Schizophrenia Patients with MEG and fMRI Data Using Static and Dynamic Connectivity Measures

PubMed Central

Cetin, Mustafa S.; Houck, Jon M.; Rashid, Barnaly; Agacoglu, Oktay; Stephen, Julia M.; Sui, Jing; Canive, Jose; Mayer, Andy; Aine, Cheryl; Bustillo, Juan R.; Calhoun, Vince D.

2016-01-01

Mental disorders like schizophrenia are currently diagnosed by physicians/psychiatrists through clinical assessment and their evaluation of patient's self-reported experiences as the illness emerges. There is great interest in identifying biological markers of prognosis at the onset of illness, rather than relying on the evolution of symptoms across time. Functional network connectivity, which indicates a subject's overall level of “synchronicity” of activity between brain regions, demonstrates promise in providing individual subject predictive power. Many previous studies reported functional connectivity changes during resting-state using only functional magnetic resonance imaging (fMRI). Nevertheless, exclusive reliance on fMRI to generate such networks may limit the inference of the underlying dysfunctional connectivity, which is hypothesized to be a factor in patient symptoms, as fMRI measures connectivity via hemodynamics. Therefore, combination of connectivity assessments using fMRI and magnetoencephalography (MEG), which more directly measures neuronal activity, may provide improved classification of schizophrenia than either modality alone. Moreover, recent evidence indicates that metrics of dynamic connectivity may also be critical for understanding pathology in schizophrenia. In this work, we propose a new framework for extraction of important disease related features and classification of patients with schizophrenia based on using both fMRI and MEG to investigate functional network components in the resting state. Results of this study show that the integration of fMRI and MEG provides important information that captures fundamental characteristics of functional network connectivity in schizophrenia and is helpful for prediction of schizophrenia patient group membership. Combined fMRI/MEG methods, using static functional network connectivity analyses, improved classification accuracy relative to use of fMRI or MEG methods alone (by 15 and 12.45%, respectively), while combined fMRI/MEG methods using dynamic functional network connectivity analyses improved classification up to 5.12% relative to use of fMRI alone and up to 17.21% relative to use of MEG alone. PMID:27807403

Perceptions of firms within a cluster regarding the cluster's function and success: Amish furniture manufacturing in Ohio

Treesearch

Matthew S. Bumgardner; Gary W. Graham; P. Charles Goebel; Robert L. Romig

2011-01-01

The Amish-based furniture manufacturing cluster in and around Holmes County, OH, is home to some 400 shops and has become an important regional driver of demand for hardwood products. The cluster has expanded even as the broader domestic furniture industry has declined. Clustering dynamics are seen as important to the success, but little information has been available...

Hydrology and microtopography control carbon dynamics in wetlands: Implications in partitioning ecosystem respiration in a coastal plain forested wetland

Treesearch

Guofang Miao; Asko Noormets; Jean-Christophe Domec; Montserrat Fuentes; Carl C. Trettin; Ge Sun; Steve G. McNulty; John S. King

2017-01-01

Wetlands store a disproportionately large fraction of organic carbon relative to their areal coverage, and thus play an important role in global climate mitigation. As destabilization of these stores through land use or en- vironmental change represents a signi fi cant climate feedback, it is important to understand the functional regulation of respiratory processes...

Germination responses to temperature and soil moisture in three species of the subfamily Caragana and their implications toward restoration in Loess-gully Region, China

Treesearch

Zhao Xiaoying; Ren Jizhou

2007-01-01

The leguminous Caragana species are important components of vegetation in the semi-arid Loess-gully region, China. These shrub species are important for maintaining the dynamics and function of the ecosystem in the region. They are potential plant resources for restoration of degraded ecosystems. The germination responses to temperatures in two...

Improved Frequency Fluctuation Model for Spectral Line Shape Calculations in Fusion Plasmas

NASA Astrophysics Data System (ADS)

Ferri, S.; Calisti, A.; Mossé, C.; Talin, B.; Lisitsa, V.

2010-10-01

A very fast method to calculate spectral line shapes emitted by plasmas accounting for charge particle dynamics and effects of an external magnetic field is proposed. This method relies on a new formulation of the Frequency Fluctuation Model (FFM), which yields to an expression of the dynamic line profile as a functional of the static distribution function of frequencies. This highly efficient formalism, not limited to hydrogen-like systems, allows to calculate pure Stark and Stark-Zeeman line shapes for a wide range of density, temperature and magnetic field values, which is of importance in plasma physics and astrophysics. Various applications of this method are presented for conditions related to fusion plasmas.

Pseudorapidity correlations in heavy ion collisions from viscous fluid dynamics

DOE PAGES

Monnai, A.; Schenke, B.

2015-11-26

We demonstrate by explicit calculations in 3+1 dimensional viscous relativistic fluid dynamics how two-particle pseudorapidity correlation functions in heavy ion collisions at the LHC and RHIC depend on the number of particle producing sources and the transport properties of the produced medium. In particular, we present results for the Legendre coefficients of the two-particle pseudorapidity correlation function, a n,m, in Pb+Pb collisions at 2760 GeV and Au+Au collisions at 200 GeV from viscous hydrodynamics with three dimensionally fluctuating initial conditions. Our results suggest that the a n,m provide important constraints on initial state fluctuations and the transport properties of themore » quark gluon plasma.« less

Determinants of Mammalian Nucleolar Architecture

PubMed Central

Farley, Katherine I.; Surovtseva, Yulia; Merkel, Janie; Baserga, Susan J.

2015-01-01

The nucleolus is responsible for the production of ribosomes, essential machines which synthesize all proteins needed by the cell. The structure of human nucleoli is highly dynamic and is directly related to its functions in ribosome biogenesis. Despite the importance of this organelle, the intricate relationship between nucleolar structure and function remains largely unexplored. How do cells control nucleolar formation and function? What are the minimal requirements for making a functional nucleolus? Here we review what is currently known regarding mammalian nucleolar formation at nucleolar organizer regions (NORs), which can be studied by observing the dissolution and reformation of the nucleolus during each cell division. Additionally, the nucleolus can be examined by analyzing how alterations in nucleolar function manifest in differences in nucleolar architecture. Furthermore, changes in nucleolar structure and function are correlated with cancer, highlighting the importance of studying the determinants of nucleolar formation. PMID:25670395

Importance of Vibronic Effects in the UV-Vis Spectrum of the 7,7,8,8-Tetracyanoquinodimethane Anion.

PubMed

Tapavicza, Enrico; Furche, Filipp; Sundholm, Dage

2016-10-11

We present a computational method for simulating vibronic absorption spectra in the ultraviolet-visible (UV-vis) range and apply it to the 7,7,8,8-tetracyanoquinodimethane anion (TCNQ - ), which has been used as a ligand in black absorbers. Gaussian broadening of vertical electronic excitation energies of TCNQ - from linear-response time-dependent density functional theory produces only one band, which is qualitatively incorrect. Thus, the harmonic vibrational modes of the two lowest doublet states were computed, and the vibronic UV-vis spectrum was simulated using the displaced harmonic oscillator approximation, the frequency-shifted harmonic oscillator approximation, and the full Duschinsky formalism. An efficient real-time generating function method was implemented to avoid the exponential complexity of conventional Franck-Condon approaches to vibronic spectra. The obtained UV-vis spectra for TCNQ - agree well with experiment; the Duschinsky rotation is found to have only a minor effect on the spectrum. Born-Oppenheimer molecular dynamics simulations combined with calculations of the electronic excitation energies for a large number of molecular structures were also used for simulating the UV-vis spectrum. The Born-Oppenheimer molecular dynamics simulations yield a broadening of the energetically lowest peak in the absorption spectrum, but additional vibrational bands present in the experimental and simulated quantum harmonic oscillator spectra are not observed in the molecular dynamics simulations. Our results underline the importance of vibronic effects for the UV-vis spectrum of TCNQ - , and they establish an efficient method for obtaining vibronic spectra using a combination of linear-response time-dependent density functional theory and a real-time generating function approach.

Flexible establishment of functional brain networks supports attentional modulation of unconscious cognition.

PubMed

Ulrich, Martin; Adams, Sarah C; Kiefer, Markus

2014-11-01

In classical theories of attention, unconscious automatic processes are thought to be independent of higher-level attentional influences. Here, we propose that unconscious processing depends on attentional enhancement of task-congruent processing pathways implemented by a dynamic modulation of the functional communication between brain regions. Using functional magnetic resonance imaging, we tested our model with a subliminally primed lexical decision task preceded by an induction task preparing either a semantic or a perceptual task set. Subliminal semantic priming was significantly greater after semantic compared to perceptual induction in ventral occipito-temporal (vOT) and inferior frontal cortex, brain areas known to be involved in semantic processing. The functional connectivity pattern of vOT varied depending on the induction task and successfully predicted the magnitude of behavioral and neural priming. Together, these findings support the proposal that dynamic establishment of functional networks by task sets is an important mechanism in the attentional control of unconscious processing. © 2014 Wiley Periodicals, Inc.

Penalized Nonlinear Least Squares Estimation of Time-Varying Parameters in Ordinary Differential Equations

PubMed Central

Cao, Jiguo; Huang, Jianhua Z.; Wu, Hulin

2012-01-01

Ordinary differential equations (ODEs) are widely used in biomedical research and other scientific areas to model complex dynamic systems. It is an important statistical problem to estimate parameters in ODEs from noisy observations. In this article we propose a method for estimating the time-varying coefficients in an ODE. Our method is a variation of the nonlinear least squares where penalized splines are used to model the functional parameters and the ODE solutions are approximated also using splines. We resort to the implicit function theorem to deal with the nonlinear least squares objective function that is only defined implicitly. The proposed penalized nonlinear least squares method is applied to estimate a HIV dynamic model from a real dataset. Monte Carlo simulations show that the new method can provide much more accurate estimates of functional parameters than the existing two-step local polynomial method which relies on estimation of the derivatives of the state function. Supplemental materials for the article are available online. PMID:23155351

The CLAIR model: Extension of Brodmann areas based on brain oscillations and connectivity.

PubMed

Başar, Erol; Düzgün, Aysel

2016-05-01

Since the beginning of the last century, the localization of brain function has been represented by Brodmann areas, maps of the anatomic organization of the brain. They are used to broadly represent cortical structures with their given sensory-cognitive functions. In recent decades, the analysis of brain oscillations has become important in the correlation of brain functions. Moreover, spectral connectivity can provide further information on the dynamic connectivity between various structures. In addition, brain responses are dynamic in nature and structural localization is almost impossible, according to Luria (1966). Therefore, brain functions are very difficult to localize; hence, a combined analysis of oscillation and event-related coherences is required. In this study, a model termed as "CLAIR" is described to enrich and possibly replace the concept of the Brodmann areas. A CLAIR model with optimum function may take several years to develop, but this study sets out to lay its foundation. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Regulatory networks and connected components of the neutral space. A look at functional islands

NASA Astrophysics Data System (ADS)

Boldhaus, G.; Klemm, K.

2010-09-01

The functioning of a living cell is largely determined by the structure of its regulatory network, comprising non-linear interactions between regulatory genes. An important factor for the stability and evolvability of such regulatory systems is neutrality - typically a large number of alternative network structures give rise to the necessary dynamics. Here we study the discretized regulatory dynamics of the yeast cell cycle [Li et al., PNAS, 2004] and the set of networks capable of reproducing it, which we call functional. Among these, the empirical yeast wildtype network is close to optimal with respect to sparse wiring. Under point mutations, which establish or delete single interactions, the neutral space of functional networks is fragmented into ≈ 4.7 × 108 components. One of the smaller ones contains the wildtype network. On average, functional networks reachable from the wildtype by mutations are sparser, have higher noise resilience and fewer fixed point attractors as compared with networks outside of this wildtype component.

Form and function in gene regulatory networks: the structure of network motifs determines fundamental properties of their dynamical state space.

PubMed

Ahnert, S E; Fink, T M A

2016-07-01

Network motifs have been studied extensively over the past decade, and certain motifs, such as the feed-forward loop, play an important role in regulatory networks. Recent studies have used Boolean network motifs to explore the link between form and function in gene regulatory networks and have found that the structure of a motif does not strongly determine its function, if this is defined in terms of the gene expression patterns the motif can produce. Here, we offer a different, higher-level definition of the 'function' of a motif, in terms of two fundamental properties of its dynamical state space as a Boolean network. One is the basin entropy, which is a complexity measure of the dynamics of Boolean networks. The other is the diversity of cyclic attractor lengths that a given motif can produce. Using these two measures, we examine all 104 topologically distinct three-node motifs and show that the structural properties of a motif, such as the presence of feedback loops and feed-forward loops, predict fundamental characteristics of its dynamical state space, which in turn determine aspects of its functional versatility. We also show that these higher-level properties have a direct bearing on real regulatory networks, as both basin entropy and cycle length diversity show a close correspondence with the prevalence, in neural and genetic regulatory networks, of the 13 connected motifs without self-interactions that have been studied extensively in the literature. © 2016 The Authors.

Controls of Isotopic Patterns in Saprotrophic and Ectomycorrhizal Fungi

EPA Science Inventory

Isotopes of nitrogen (δ15N) and carbon (δ13C) in ectomycorrhizal and saprotrophic fungi contain important information about ecological functioning, but the complexity of physiological and ecosystem processes contributing to fungal carbon and nitrogen dynamics has limited our abil...

Kinetic theory for strongly coupled Coulomb systems

NASA Astrophysics Data System (ADS)

Dufty, James; Wrighton, Jeffrey

2018-01-01

The calculation of dynamical properties for matter under extreme conditions is a challenging task. The popular Kubo-Greenwood model exploits elements from equilibrium density-functional theory (DFT) that allow a detailed treatment of electron correlations, but its origin is largely phenomenological; traditional kinetic theories have a more secure foundation but are limited to weak ion-electron interactions. The objective here is to show how a combination of the two evolves naturally from the short-time limit for the generator of the effective single-electron dynamics governing time correlation functions without such limitations. This provides a theoretical context for the current DFT-related approach, the Kubo-Greenwood model, while showing the nature of its corrections. The method is to calculate the short-time dynamics in the single-electron subspace for a given configuration of the ions. This differs from the usual kinetic theory approach in which an average over the ions is performed as well. In this way the effective ion-electron interaction includes strong Coulomb coupling and is shown to be determined from DFT. The correlation functions have the form of the random-phase approximation for an inhomogeneous system but with renormalized ion-electron and electron-electron potentials. The dynamic structure function, density response function, and electrical conductivity are calculated as examples. The static local field corrections in the dielectric function are identified in this way. The current analysis is limited to semiclassical electrons (quantum statistical potentials), so important quantum conditions are excluded. However, a quantization of the kinetic theory is identified for broader application while awaiting its detailed derivation.

Modelling and enhanced molecular dynamics to steer structure-based drug discovery.

PubMed

Kalyaanamoorthy, Subha; Chen, Yi-Ping Phoebe

2014-05-01

The ever-increasing gap between the availabilities of the genome sequences and the crystal structures of proteins remains one of the significant challenges to the modern drug discovery efforts. The knowledge of structure-dynamics-functionalities of proteins is important in order to understand several key aspects of structure-based drug discovery, such as drug-protein interactions, drug binding and unbinding mechanisms and protein-protein interactions. This review presents a brief overview on the different state of the art computational approaches that are applied for protein structure modelling and molecular dynamics simulations of biological systems. We give an essence of how different enhanced sampling molecular dynamics approaches, together with regular molecular dynamics methods, assist in steering the structure based drug discovery processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Universal scaling in the aging of the strong glass former SiO{sub 2}

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

Vollmayr-Lee, Katharina, E-mail: kvollmay@bucknell.edu; Gorman, Christopher H.; Castillo, Horacio E.

We show that the aging dynamics of a strong glass former displays a strikingly simple scaling behavior, connecting the average dynamics with its fluctuations, namely, the dynamical heterogeneities. We perform molecular dynamics simulations of SiO{sub 2} with van Beest-Kramer-van Santen interactions, quenching the system from high to low temperature, and study the evolution of the system as a function of the waiting time t{sub w} measured from the instant of the quench. We find that both the aging behavior of the dynamic susceptibility χ{sub 4} and the aging behavior of the probability distribution P(f{sub s,r}) of the local incoherent intermediatemore » scattering function f{sub s,r} can be described by simple scaling forms in terms of the global incoherent intermediate scattering function C. The scaling forms are the same that have been found to describe the aging of several fragile glass formers and that, in the case of P(f{sub s,r}), have been also predicted theoretically. A thorough study of the length scales involved highlights the importance of intermediate length scales. We also analyze directly the scaling dependence on particle type and on wavevector q and find that both the average and the fluctuations of the slow aging dynamics are controlled by a unique aging clock, which is not only independent of the wavevector q, but is also the same for O and Si atoms.« less

The promotion of cooperation by the poor in dynamic chicken games

NASA Astrophysics Data System (ADS)

Ito, Hiromu; Katsumata, Yuki; Hasegawa, Eisuke; Yoshimura, Jin

2017-02-01

The evolution of cooperative behavior is one of the most important issues in game theory. Previous studies have shown that cooperation can evolve only under highly limited conditions, and various modifications have been introduced to games to explain the evolution of cooperation. Recently, a utility function basic to game theory was shown to be dependent on current wealth as a conditional (state) variable in a dynamic version of utility theory. Here, we introduce this dynamic utility function to several games. Under certain conditions, poor players exhibit cooperative behavior in two types of chicken games (the hawk-dove game and the snowdrift game) but not in the prisoner’s dilemma game and the stag hunt game. This result indicates that cooperation can be exhibited by the poor in some chicken games. Thus, the evolution of cooperation may not be as limited as has been suggested in previous studies.

Crossover in growth laws for phase-separating binary fluids: molecular dynamics simulations.

PubMed

Ahmad, Shaista; Das, Subir K; Puri, Sanjay

2012-03-01

Pattern and dynamics during phase separation in a symmetrical binary (A+B) Lennard-Jones fluid are studied via molecular dynamics simulations after quenching homogeneously mixed critical (50:50) systems to temperatures below the critical one. The morphology of the domains, rich in A or B particles, is observed to be bicontinuous. The early-time growth of the average domain size is found to be consistent with the Lifshitz-Slyozov law for diffusive domain coarsening. After a characteristic time, dependent on the temperature, we find a clear crossover to an extended viscous hydrodynamic regime where the domains grow linearly with time. Pattern formation in the present system is compared with that in solid binary mixtures, as a function of temperature. Important results for the finite-size and temperature effects on the small-wave-vector behavior of the scattering function are also presented.

Universal evaporation dynamics of a confined sessile droplet

NASA Astrophysics Data System (ADS)

Bansal, Lalit; Hatte, Sandeep; Basu, Saptarshi; Chakraborty, Suman

2017-09-01

Droplet evaporation under confinement is ubiquitous to multitude of applications such as microfluidics, surface patterning, and ink-jet printing. However, the rich physics governing the universality in the underlying dynamics remains grossly elusive. Here, we bring out hitherto unexplored universal features of the evaporation dynamics of a sessile droplet entrapped in a 3D confined fluidic environment. We show, through extensive set of experiments and theoretical formulations, that the evaporation timescale for such a droplet can be represented by a unique function of the initial conditions. Moreover, using same theoretical considerations, we are able to trace and universally merge the volume evolution history of the droplets along with evaporation lifetimes, irrespective of the extent of confinement. We also showcase the internal flow transitions caused by spatio-temporal variation of evaporation flux due to confinement. These findings may be of profound importance in designing functionalized droplet evaporation devices for emerging engineering and biomedical applications.

Free energy reconstruction from steered dynamics without post-processing

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

Athenes, Manuel, E-mail: Manuel.Athenes@cea.f; Condensed Matter and Materials Division, Physics and Life Sciences Directorate, LLNL, Livermore, CA 94551; Marinica, Mihai-Cosmin

2010-09-20

Various methods achieving importance sampling in ensembles of nonequilibrium trajectories enable one to estimate free energy differences and, by maximum-likelihood post-processing, to reconstruct free energy landscapes. Here, based on Bayes theorem, we propose a more direct method in which a posterior likelihood function is used both to construct the steered dynamics and to infer the contribution to equilibrium of all the sampled states. The method is implemented with two steering schedules. First, using non-autonomous steering, we calculate the migration barrier of the vacancy in Fe-{alpha}. Second, using an autonomous scheduling related to metadynamics and equivalent to temperature-accelerated molecular dynamics, wemore » accurately reconstruct the two-dimensional free energy landscape of the 38-atom Lennard-Jones cluster as a function of an orientational bond-order parameter and energy, down to the solid-solid structural transition temperature of the cluster and without maximum-likelihood post-processing.« less

Activity-Dependence of Synaptic Vesicle Dynamics

PubMed Central

Forte, Luca A.

2017-01-01

The proper function of synapses relies on efficient recycling of synaptic vesicles. The small size of synaptic boutons has hampered efforts to define the dynamical states of vesicles during recycling. Moreover, whether vesicle motion during recycling is regulated by neural activity remains largely unknown. We combined nanoscale-resolution tracking of individual synaptic vesicles in cultured hippocampal neurons from rats of both sexes with advanced motion analyses to demonstrate that the majority of recently endocytosed vesicles undergo sequences of transient dynamical states including epochs of directed, diffusional, and stalled motion. We observed that vesicle motion is modulated in an activity-dependent manner, with dynamical changes apparent in ∼20% of observed boutons. Within this subpopulation of boutons, 35% of observed vesicles exhibited acceleration and 65% exhibited deceleration, accompanied by corresponding changes in directed motion. Individual vesicles observed in the remaining ∼80% of boutons did not exhibit apparent dynamical changes in response to stimulation. More quantitative transient motion analyses revealed that the overall reduction of vesicle mobility, and specifically of the directed motion component, is the predominant activity-evoked change across the entire bouton population. Activity-dependent modulation of vesicle mobility may represent an important mechanism controlling vesicle availability and neurotransmitter release. SIGNIFICANCE STATEMENT Mechanisms governing synaptic vesicle dynamics during recycling remain poorly understood. Using nanoscale resolution tracking of individual synaptic vesicles in hippocampal synapses and advanced motion analysis tools we demonstrate that synaptic vesicles undergo complex sets of dynamical states that include epochs of directed, diffusive, and stalled motion. Most importantly, our analyses revealed that vesicle motion is modulated in an activity-dependent manner apparent as the reduction in overall vesicle mobility in response to stimulation. These results define the vesicle dynamical states during recycling and reveal their activity-dependent modulation. Our study thus provides fundamental new insights into the principles governing synaptic function. PMID:28954868

Can visco-elastic phase separation, macromolecular crowding and colloidal physics explain nuclear organisation?

PubMed

Iborra, Francisco J

2007-04-12

The cell nucleus is highly compartmentalized with well-defined domains, it is not well understood how this nuclear order is maintained. Many scientists are fascinated by the different set of structures observed in the nucleus to attribute functions to them. In order to distinguish functional compartments from non-functional aggregates, I believe is important to investigate the biophysical nature of nuclear organisation. The various nuclear compartments can be divided broadly as chromatin or protein and/or RNA based, and they have very different dynamic properties. The chromatin compartment displays a slow, constrained diffusional motion. On the other hand, the protein/RNA compartment is very dynamic. Physical systems with dynamical asymmetry go to viscoelastic phase separation. This phase separation phenomenon leads to the formation of a long-lived interaction network of slow components (chromatin) scattered within domains rich in fast components (protein/RNA). Moreover, the nucleus is packed with macromolecules in the order of 300 mg/ml. This high concentration of macromolecules produces volume exclusion effects that enhance attractive interactions between macromolecules, known as macromolecular crowding, which favours the formation of compartments. In this paper I hypothesise that nuclear compartmentalization can be explained by viscoelastic phase separation of the dynamically different nuclear components, in combination with macromolecular crowding and the properties of colloidal particles. I demonstrate that nuclear structure can satisfy the predictions of this hypothesis. I discuss the functional implications of this phenomenon.

Disrupted brain network functional dynamics and hyper-correlation of structural and functional connectome topology in patients with breast cancer prior to treatment.

PubMed

Kesler, Shelli R; Adams, Marjorie; Packer, Melissa; Rao, Vikram; Henneghan, Ashley M; Blayney, Douglas W; Palesh, Oxana

2017-03-01

Several previous studies have demonstrated that cancer chemotherapy is associated with brain injury and cognitive dysfunction. However, evidence suggests that cancer pathogenesis alone may play a role, even in non-CNS cancers. Using a multimodal neuroimaging approach, we measured structural and functional connectome topology as well as functional network dynamics in newly diagnosed patients with breast cancer. Our study involved a novel, pretreatment assessment that occurred prior to the initiation of any cancer therapies, including surgery with anesthesia. We enrolled 74 patients with breast cancer age 29-65 and 50 frequency-matched healthy female controls who underwent anatomic and resting-state functional MRI as well as cognitive testing. Compared to controls, patients with breast cancer demonstrated significantly lower functional network dynamics ( p  = .046) and cognitive functioning ( p  < .02, corrected). The breast cancer group also showed subtle alterations in structural local clustering and functional local clustering ( p  < .05, uncorrected) as well as significantly increased correlation between structural global clustering and functional global clustering compared to controls ( p  = .03). This hyper-correlation between structural and functional topologies was significantly associated with cognitive dysfunction ( p  = .005). Our findings could not be accounted for by psychological distress and suggest that non-CNS cancer may directly and/or indirectly affect the brain via mechanisms such as tumor-induced neurogenesis, inflammation, and/or vascular changes, for example. Our results also have broader implications concerning the importance of the balance between structural and functional connectome properties as a potential biomarker of general neurologic deficit.

Effect of β-blockade on lung function, exercise performance and dynamic hyperinflation in people with arterial vascular disease with and without COPD.

PubMed

Key, Angela; Parry, Matthew; West, Malcolm A; Asher, Rebecca; Jack, Sandy; Duffy, Nick; Torella, Francesco; Walker, Paul P

2017-01-01

β Blockers are important treatment for ischaemic heart disease and heart failure; however, there has long been concern about their use in people with chronic obstructive pulmonary disease (COPD) due to fear of symptomatic worsening of breathlessness. Despite growing evidence of safety and efficacy, they remain underused. We examined the effect of β-blockade on lung function, exercise performance and dynamic hyperinflation in a group of vascular surgical patients, a high proportion of who were expected to have COPD. People undergoing routine abdominal aortic aneurysm (AAA) surveillance were sequentially recruited from vascular surgery clinic. They completed plethysmographically measured lung function and incremental cardiopulmonary exercise testing with dynamic measurement of inspiratory capacity while taking and not taking β blocker. 48 participants completed tests while taking and not taking β blockers with 38 completing all assessments successfully. 15 participants (39%) were found to have, predominantly mild and undiagnosed, COPD. People with COPD had airflow obstruction, increased airway resistance (Raw) and specific conductance (sGaw), static hyperinflation and dynamically hyperinflated during exercise. In the whole group, β-blockade led to a small fall in FEV1 (0.1 L/2.8% predicted) but did not affect Raw, sGaw, static or dynamic hyperinflation. No difference in response to β-blockade was seen in those with and without COPD. In people with AAA, β-blockade has little effect on lung function and dynamic hyperinflation in those with and without COPD. In this population, the prevalence of COPD is high and consideration should be given to case finding with spirometry. NCT02106286.

Particle swarm optimization with recombination and dynamic linkage discovery.

PubMed

Chen, Ying-Ping; Peng, Wen-Chih; Jian, Ming-Chung

2007-12-01

In this paper, we try to improve the performance of the particle swarm optimizer by incorporating the linkage concept, which is an essential mechanism in genetic algorithms, and design a new linkage identification technique called dynamic linkage discovery to address the linkage problem in real-parameter optimization problems. Dynamic linkage discovery is a costless and effective linkage recognition technique that adapts the linkage configuration by employing only the selection operator without extra judging criteria irrelevant to the objective function. Moreover, a recombination operator that utilizes the discovered linkage configuration to promote the cooperation of particle swarm optimizer and dynamic linkage discovery is accordingly developed. By integrating the particle swarm optimizer, dynamic linkage discovery, and recombination operator, we propose a new hybridization of optimization methodologies called particle swarm optimization with recombination and dynamic linkage discovery (PSO-RDL). In order to study the capability of PSO-RDL, numerical experiments were conducted on a set of benchmark functions as well as on an important real-world application. The benchmark functions used in this paper were proposed in the 2005 Institute of Electrical and Electronics Engineers Congress on Evolutionary Computation. The experimental results on the benchmark functions indicate that PSO-RDL can provide a level of performance comparable to that given by other advanced optimization techniques. In addition to the benchmark, PSO-RDL was also used to solve the economic dispatch (ED) problem for power systems, which is a real-world problem and highly constrained. The results indicate that PSO-RDL can successfully solve the ED problem for the three-unit power system and obtain the currently known best solution for the 40-unit system.

The Importance of Three-Body Interactions in Molecular Dynamics Simulations of Water with the Fragment Molecular Orbital Method

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

Pruitt, Spencer R.; Nakata, Hiroya; Nagata, Takeshi

2016-04-12

The analytic first derivative with respect to nuclear coordinates is formulated and implemented in the framework of the three-body fragment molecular orbital (FMO) method. The gradient has been derived and implemented for restricted Hartree-Fock, second-order Møller-Plesset perturbation, and density functional theories. The importance of the three-body fully analytic gradient is illustrated through the failure of the two-body FMO method during molecular dynamics simulations of a small water cluster. The parallel implementation of the fragment molecular orbital method, its parallel efficiency, and its scalability on the Blue Gene/Q architecture up to 262,144 CPU cores, are also discussed.

Characterization of dynamic physiology of the bladder by optical coherence tomography

NASA Astrophysics Data System (ADS)

Yuan, Zhijia; Keng, Kerri; Pan, Rubin; Ren, Hugang; Du, Congwu; Kim, Jason; Pan, Yingtian

2012-03-01

Because of its high spatial resolution and noninvasive imaging capabilities, optical coherence tomography has been used to characterize the morphological details of various biological tissues including urinary bladder and to diagnose their alternations (e.g., cancers). In addition to static morphology, the dynamic features of tissue morphology can provide important information that can be used to diagnose the physiological and functional characteristics of biological tissues. Here, we present the imaging studies based on optical coherence tomography to characterize motion related physiology and functions of rat bladder detrusor muscles and compared the results with traditional biomechanical measurements. Our results suggest that optical coherence tomography is capable of providing quantitative evaluation of contractile functions of intact bladder (without removing bladder epithelium and connective tissue), which is potentially of more clinical relevance for future clinical diagnosis - if incorporated with cystoscopic optical coherence tomography.

Polymeric Biomaterials: Diverse Functions Enabled by Advances in Macromolecular Chemistry

PubMed Central

Liang, Yingkai; Li, Linqing; Scott, Rebecca A.; Kiick, Kristi L.

2017-01-01

Biomaterials have been extensively used to leverage beneficial outcomes in various therapeutic applications, such as providing spatial and temporal control over the release of therapeutic agents in drug delivery as well as engineering functional tissues and promoting the healing process in tissue engineering and regenerative medicine. This perspective presents important milestones in the development of polymeric biomaterials with defined structures and properties. Contemporary studies of biomaterial design have been reviewed with focus on constructing materials with controlled structure, dynamic functionality, and biological complexity. Examples of these polymeric biomaterials enabled by advanced synthetic methodologies, dynamic chemistry/assembly strategies, and modulated cell-material interactions have been highlighted. As the field of polymeric biomaterials continues to evolve with increased sophistication, current challenges and future directions for the design and translation of these materials are also summarized. PMID:29151616

Connectivity dynamics in typical development and its relationship to autistic traits and autism spectrum disorder.

PubMed

Rashid, Barnaly; Blanken, Laura M E; Muetzel, Ryan L; Miller, Robyn; Damaraju, Eswar; Arbabshirani, Mohammad R; Erhardt, Erik B; Verhulst, Frank C; van der Lugt, Aad; Jaddoe, Vincent W V; Tiemeier, Henning; White, Tonya; Calhoun, Vince

2018-03-30

Recent advances in neuroimaging techniques have provided significant insights into developmental trajectories of human brain function. Characterizations of typical neurodevelopment provide a framework for understanding altered neurodevelopment, including differences in brain function related to developmental disorders and psychopathology. Historically, most functional connectivity studies of typical and atypical development operate under the assumption that connectivity remains static over time. We hypothesized that relaxing stationarity assumptions would reveal novel features of both typical brain development related to children on the autism spectrum. We employed a "chronnectomic" (recurring, time-varying patterns of connectivity) approach to evaluate transient states of connectivity using resting-state functional MRI in a population-based sample of 774 6- to 10-year-old children. Dynamic connectivity was evaluated using a sliding-window approach, and revealed four transient states. Internetwork connectivity increased with age in modularized dynamic states, illustrating an important pattern of connectivity in the developing brain. Furthermore, we demonstrated that higher levels of autistic traits and ASD diagnosis were associated with longer dwell times in a globally disconnected state. These results provide a roadmap to the chronnectomic organization of the developing brain and suggest that characteristics of functional brain connectivity are related to children on the autism spectrum. © 2018 Wiley Periodicals, Inc.

Replicability of time-varying connectivity patterns in large resting state fMRI samples.

PubMed

Abrol, Anees; Damaraju, Eswar; Miller, Robyn L; Stephen, Julia M; Claus, Eric D; Mayer, Andrew R; Calhoun, Vince D

2017-12-01

The past few years have seen an emergence of approaches that leverage temporal changes in whole-brain patterns of functional connectivity (the chronnectome). In this chronnectome study, we investigate the replicability of the human brain's inter-regional coupling dynamics during rest by evaluating two different dynamic functional network connectivity (dFNC) analysis frameworks using 7 500 functional magnetic resonance imaging (fMRI) datasets. To quantify the extent to which the emergent functional connectivity (FC) patterns are reproducible, we characterize the temporal dynamics by deriving several summary measures across multiple large, independent age-matched samples. Reproducibility was demonstrated through the existence of basic connectivity patterns (FC states) amidst an ensemble of inter-regional connections. Furthermore, application of the methods to conservatively configured (statistically stationary, linear and Gaussian) surrogate datasets revealed that some of the studied state summary measures were indeed statistically significant and also suggested that this class of null model did not explain the fMRI data fully. This extensive testing of reproducibility of similarity statistics also suggests that the estimated FC states are robust against variation in data quality, analysis, grouping, and decomposition methods. We conclude that future investigations probing the functional and neurophysiological relevance of time-varying connectivity assume critical importance. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Replicability of time-varying connectivity patterns in large resting state fMRI samples

PubMed Central

Abrol, Anees; Damaraju, Eswar; Miller, Robyn L.; Stephen, Julia M.; Claus, Eric D.; Mayer, Andrew R.; Calhoun, Vince D.

2018-01-01

The past few years have seen an emergence of approaches that leverage temporal changes in whole-brain patterns of functional connectivity (the chronnectome). In this chronnectome study, we investigate the replicability of the human brain’s inter-regional coupling dynamics during rest by evaluating two different dynamic functional network connectivity (dFNC) analysis frameworks using 7 500 functional magnetic resonance imaging (fMRI) datasets. To quantify the extent to which the emergent functional connectivity (FC) patterns are reproducible, we characterize the temporal dynamics by deriving several summary measures across multiple large, independent age-matched samples. Reproducibility was demonstrated through the existence of basic connectivity patterns (FC states) amidst an ensemble of inter-regional connections. Furthermore, application of the methods to conservatively configured (statistically stationary, linear and Gaussian) surrogate datasets revealed that some of the studied state summary measures were indeed statistically significant and also suggested that this class of null model did not explain the fMRI data fully. This extensive testing of reproducibility of similarity statistics also suggests that the estimated FC states are robust against variation in data quality, analysis, grouping, and decomposition methods. We conclude that future investigations probing the functional and neurophysiological relevance of time-varying connectivity assume critical importance. PMID:28916181

The role of nonbonded interactions in the conformational dynamics of organophosphorous hydrolase adsorbed onto functionalized mesoporous silica surfaces.

PubMed

Gomes, Diego E B; Lins, Roberto D; Pascutti, Pedro G; Lei, Chenghong; Soares, Thereza A

2010-01-14

The enzyme organophosphorous hydrolase (OPH) catalyzes the hydrolysis of a wide variety of organophosphorous compounds with high catalytic efficiency and broad substrate specificity. The immobilization of OPH in functionalized mesoporous silica (FMS) surfaces increases significantly its catalytic specific activity, as compared to the enzyme in solution, with important applications for the detection and decontamination of insecticides and chemical warfare agents. Experimental measurements of immobilization efficiency as a function of the charge and coverage percentage of different functional groups have been interpreted as electrostatic forces being the predominant interactions underlying the adsorption of OPH onto FMS surfaces. Explicit solvent molecular dynamics simulations have been performed for OPH in bulk solution and adsorbed onto two distinct interaction potential models of the FMS functional groups to investigate the relative contributions of nonbonded interactions to the conformational dynamics and adsorption of the protein. Our results support the conclusion that electrostatic interactions are responsible for the binding of OPH to the FMS surface. However, these results also show that van der Waals forces are detrimental for interfacial adhesion. In addition, it is found that OPH adsorption onto the FMS models favors a protein conformation whose active site is fully accessible to the substrate, in contrast to the unconfined protein.

Functional nucleic acids as in vivo metabolite and ion biosensors.

PubMed

Alsaafin, Alaa; McKeague, Maureen

2017-08-15

Characterizing the role of metabolites, metals, and proteins is required to understand normal cell function, and ultimately, elucidate the mechanism of disease. Metabolite concentration and transformation results collected from cell lysates or fixed-cells conceal important dynamic information and differences between individual cells that often have profound functional consequences. Functional nucleic acid-based biosensors are emerging tools that are capable of monitoring ions and metabolites in cell populations or whole animals. Functional nucleic acids (FNAs) are a class of biomolecules that can exhibit either ligand binding or enzymatic activity. Unlike their protein analogues or the use of instrument-based analysis, FNA-based biosensors are capable of entering cells without disruption to the cellular environment and can report on the concentration, dynamics, and spatial localization of molecules in cells. Here, we review the types of FNAs that have been used as in vivo biosensors, and how FNAs can be coupled to transduction systems and delivered inside cells. We also provide examples from the literature that demonstrate their impact in practical applications. Finally, we comment on the critical limitations that need to be addressed to enable their use for single-cell dynamic tracking of metabolites and ions in vivo. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Tools for assessing mitochondrial dynamics in mouse tissues and neurodegenerative models

NASA Astrophysics Data System (ADS)

Pham, Anh H.

Mitochondria are dynamic organelles that undergo membrane fusion and fission and transport. The dynamic properties of mitochondria are important for regulating mitochondrial function. Defects in mitochondrial dynamics are linked neurodegenerative diseases and affect the development of many tissues. To investigate the role of mitochondrial dynamics in diseases, versatile tools are needed to explore the physiology of these dynamic organelles in multiple tissues. Current tools for monitoring mitochondrial dynamics have been limited to studies in cell culture, which may be inadequate model systems for exploring the network of tissues. Here, we have generated mouse models for monitoring mitochondrial dynamics in a broad spectrum of tissues and cell types. The Photo-Activatable Mitochondrial (PhAM floxed) line enables Cre-inducible expression of a mitochondrial targeted photoconvertible protein, Dendra2 (mito-Dendra2). In the PhAMexcised line, mito-Dendra2 is ubiquitously expressed to facilitate broad analysis of mitochondria at various developmental processes. We have utilized these models to study mitochondrial dynamics in the nigrostriatal circuit of Parkinson's disease (PD) and in the development of skeletal muscles. Increasing evidences implicate aberrant regulation of mitochondrial fusion and fission in models of PD. To assess the function of mitochondrial dynamics in the nigrostriatal circuit, we utilized transgenic techniques to abrogate mitochondrial fusion. We show that deletion of the Mfn2 leads to the degeneration of dopaminergic neurons and Parkinson's-like features in mice. To elucidate the dynamic properties of mitochondria during muscle development, we established a platform for examining mitochondrial compartmentalization in skeletal muscles. This model system may yield clues to the role of mitochondrial dynamics in mitochondrial myopathies.

What kind of noise is brain noise: anomalous scaling behavior of the resting brain activity fluctuations

PubMed Central

Fraiman, Daniel; Chialvo, Dante R.

2012-01-01

The study of spontaneous fluctuations of brain activity, often referred as brain noise, is getting increasing attention in functional magnetic resonance imaging (fMRI) studies. Despite important efforts, much of the statistical properties of such fluctuations remain largely unknown. This work scrutinizes these fluctuations looking at specific statistical properties which are relevant to clarify its dynamical origins. Here, three statistical features which clearly differentiate brain data from naive expectations for random processes are uncovered: First, the variance of the fMRI mean signal as a function of the number of averaged voxels remains constant across a wide range of observed clusters sizes. Second, the anomalous behavior of the variance is originated by bursts of synchronized activity across regions, regardless of their widely different sizes. Finally, the correlation length (i.e., the length at which the correlation strength between two regions vanishes) as well as mutual information diverges with the cluster's size considered, such that arbitrarily large clusters exhibit the same collective dynamics than smaller ones. These three properties are known to be exclusive of complex systems exhibiting critical dynamics, where the spatio-temporal dynamics show these peculiar type of fluctuations. Thus, these findings are fully consistent with previous reports of brain critical dynamics, and are relevant for the interpretation of the role of fluctuations and variability in brain function in health and disease. PMID:22934058

Microscopic derivation of particle-based coarse-grained dynamics: Exact expression for memory function

NASA Astrophysics Data System (ADS)

Izvekov, Sergei

2017-03-01

We consider the generalized Langevin equations of motion describing exactly the particle-based coarse-grained dynamics in the classical microscopic ensemble that were derived recently within the Mori-Zwanzig formalism based on new projection operators [S. Izvekov, J. Chem. Phys. 138(13), 134106 (2013)]. The fundamental difference between the new family of projection operators and the standard Zwanzig projection operator used in the past to derive the coarse-grained equations of motion is that the new operators average out the explicit irrelevant trajectories leading to the possibility of solving the projected dynamics exactly. We clarify the definition of the projection operators and revisit the formalism to compute the projected dynamics exactly for the microscopic system in equilibrium. The resulting expression for the projected force is in the form of a "generalized additive fluctuating force" describing the departure of the generalized microscopic force associated with the coarse-grained coordinate from its projection. Starting with this key expression, we formulate a new exact formula for the memory function in terms of microscopic and coarse-grained conservative forces. We conclude by studying two independent limiting cases of practical importance: the Markov limit (vanishing correlations of projected force) and the limit of weak dependence of the memory function on the particle momenta. We present computationally affordable expressions which can be efficiently evaluated from standard molecular dynamics simulations.

Modeling the Dynamics of Soil Structure and Water in Agricultural Soil

NASA Astrophysics Data System (ADS)

Weller, U.; Lang, B.; Rabot, E.; Stössel, B.; Urbanski, L.; Vogel, H. J.; Wiesmeier, M.; Wollschlaeger, U.

2017-12-01

The impact of agricultural management on soil functions is manifold and severe. It has both positive and adverse influence. Our goal is to develop model tools quantifying the agricultural impact on soil functions based on a mechanistic understanding of soil processes to support farmers and decision makers. The modeling approach is based on defining relevant soil components, i.e. soil matrix, macropores, organisms, roots and organic matter. They interact and form the soil's macroscopic properties and functions including water and gas dynamics, and biochemical cycles. Based on existing literature information we derive functional interaction processes and combine them in a network of dynamic soil components. In agricultural soils, a major issue is linked to changes in soil structure and their influence on water dynamics. Compaction processes are well studied in literature, but for the resilience due to root growth and activity of soil organisms the information is scarcer. We implement structural dynamics into soil water and gas simulations using a lumped model that is both coarse enough to allow extensive model runs while still preserving some important, yet rarely modeled phenomenons like preferential flow, hysteretic and dynamic behavior. For simulating water dynamics, at each depth, the model assumes water at different binding energies depending on soil structure, i.e. the pore size distribution. Non-equilibrium is postulated, meaning that free water may occur even if the soil is not fully saturated. All energy levels are interconnected allowing water to move, both within a spatial node, and between neighboring nodes (adding gravity). Structure dynamics alters the capacity of this water compartments, and the conductance of its connections. Connections are switched on and off depending on whether their sources contain water or their targets have free capacity. This leads to piecewise linear system behavior that allows fast calculation for extended time steps. Based on this concept, the dynamics of soil structure can be directly linked to soil water dynamics as a main driver for other soil processes. Further steps will include integration of temperature and solute leaching as well as defining the feedback of the water regime on the structure forming processes.

Future Carbon Dynamics of the Northern Rockies Ecoregion due to Climate Impacts and Fire Effects

NASA Astrophysics Data System (ADS)

Weller, U.; Lang, B.; Rabot, E.; Stössel, B.; Urbanski, L.; Vogel, H. J.; Wiesmeier, M.; Wollschlaeger, U.

2016-12-01

The impact of agricultural management on soil functions is manifold and severe. It has both positive and adverse influence. Our goal is to develop model tools quantifying the agricultural impact on soil functions based on a mechanistic understanding of soil processes to support farmers and decision makers. The modeling approach is based on defining relevant soil components, i.e. soil matrix, macropores, organisms, roots and organic matter. They interact and form the soil's macroscopic properties and functions including water and gas dynamics, and biochemical cycles. Based on existing literature information we derive functional interaction processes and combine them in a network of dynamic soil components. In agricultural soils, a major issue is linked to changes in soil structure and their influence on water dynamics. Compaction processes are well studied in literature, but for the resilience due to root growth and activity of soil organisms the information is scarcer. We implement structural dynamics into soil water and gas simulations using a lumped model that is both coarse enough to allow extensive model runs while still preserving some important, yet rarely modeled phenomenons like preferential flow, hysteretic and dynamic behavior. For simulating water dynamics, at each depth, the model assumes water at different binding energies depending on soil structure, i.e. the pore size distribution. Non-equilibrium is postulated, meaning that free water may occur even if the soil is not fully saturated. All energy levels are interconnected allowing water to move, both within a spatial node, and between neighboring nodes (adding gravity). Structure dynamics alters the capacity of this water compartments, and the conductance of its connections. Connections are switched on and off depending on whether their sources contain water or their targets have free capacity. This leads to piecewise linear system behavior that allows fast calculation for extended time steps. Based on this concept, the dynamics of soil structure can be directly linked to soil water dynamics as a main driver for other soil processes. Further steps will include integration of temperature and solute leaching as well as defining the feedback of the water regime on the structure forming processes.

Biodiversity and ecosystem functioning in dynamic landscapes

PubMed Central

Brose, Ulrich; Hillebrand, Helmut

2016-01-01

The relationship between biodiversity and ecosystem functioning (BEF) and its consequence for ecosystem services has predominantly been studied by controlled, short-term and small-scale experiments under standardized environmental conditions and constant community compositions. However, changes in biodiversity occur in real-world ecosystems with varying environments and a dynamic community composition. In this theme issue, we present novel research on BEF in such dynamic communities. The contributions are organized in three sections on BEF relationships in (i) multi-trophic diversity, (ii) non-equilibrium biodiversity under disturbance and varying environmental conditions, and (iii) large spatial and long temporal scales. The first section shows that multi-trophic BEF relationships often appear idiosyncratic, while accounting for species traits enables a predictive understanding. Future BEF research on complex communities needs to include ecological theory that is based on first principles of species-averaged body masses, stoichiometry and effects of environmental conditions such as temperature. The second section illustrates that disturbance and varying environments have direct as well as indirect (via changes in species richness, community composition and species' traits) effects on BEF relationships. Fluctuations in biodiversity (species richness, community composition and also trait dominance within species) can severely modify BEF relationships. The third section demonstrates that BEF at larger spatial scales is driven by different variables. While species richness per se and community biomass are most important, species identity effects and community composition are less important than at small scales. Across long temporal scales, mass extinctions represent severe changes in biodiversity with mixed effects on ecosystem functions. Together, the contributions of this theme issue identify new research frontiers and answer some open questions on BEF relationships in dynamic communities of real-world landscapes. PMID:27114570

Host-parasite oscillation dynamics and evolution in a compartmentalized RNA replication system.

PubMed

Bansho, Yohsuke; Furubayashi, Taro; Ichihashi, Norikazu; Yomo, Tetsuya

2016-04-12

To date, various cellular functions have been reconstituted in vitro such as self-replication systems using DNA, RNA, and proteins. The next important challenges include the reconstitution of the interactive networks of self-replicating species and investigating how such interactions generate complex ecological behaviors observed in nature. Here, we synthesized a simple replication system composed of two self-replicating host and parasitic RNA species. We found that the parasitic RNA eradicates the host RNA under bulk conditions; however, when the system is compartmentalized, a continuous oscillation pattern in the population dynamics of the two RNAs emerges. The oscillation pattern changed as replication proceeded mainly owing to the evolution of the host RNA. These results demonstrate that a cell-like compartment plays an important role in host-parasite ecological dynamics and suggest that the origin of the host-parasite coevolution might date back to the very early stages of the evolution of life.

Towards a self-consistent dynamical nuclear model

NASA Astrophysics Data System (ADS)

Roca-Maza, X.; Niu, Y. F.; Colò, G.; Bortignon, P. F.

2017-04-01

Density functional theory (DFT) is a powerful and accurate tool, exploited in nuclear physics to investigate the ground-state and some of the collective properties of nuclei along the whole nuclear chart. Models based on DFT are not, however, suitable for the description of single-particle dynamics in nuclei. Following the field theoretical approach by A Bohr and B R Mottelson to describe nuclear interactions between single-particle and vibrational degrees of freedom, we have taken important steps towards the building of a microscopic dynamic nuclear model. In connection with this, one important issue that needs to be better understood is the renormalization of the effective interaction in the particle-vibration approach. One possible way to renormalize the interaction is by the so-called subtraction method. In this contribution, we will implement the subtraction method in our model for the first time and study its consequences.

Visualization of Notch signaling oscillation in cells and tissues.

PubMed

Shimojo, Hiromi; Harima, Yukiko; Kageyama, Ryoichiro

2014-01-01

The Notch signaling effectors Hes1 and Hes7 exhibit oscillatory expression with a period of about 2-3 h during embryogenesis. Hes1 oscillation is important for proliferation and differentiation of neural stem cells, whereas Hes7 oscillation regulates periodic formation of somites. Continuous expression of Hes1 and Hes7 inhibits these developmental processes. Thus, expression dynamics are very important for gene functions, but it is difficult to distinguish between oscillatory and persistent expression by conventional methods such as in situ hybridization and immunostaining. Here, we describe time-lapse imaging methods using destabilized luciferase reporters and a highly sensitive cooled charge-coupled device camera, which can monitor dynamic gene expression. Furthermore, the expression of two genes can be examined simultaneously by a dual reporter system using two-color luciferase reporters. Time-lapse imaging analyses reveal how dynamically gene expression changes in many biological events.

LeuT conformational sampling utilizing accelerated molecular dynamics and principal component analysis.

PubMed

Thomas, James R; Gedeon, Patrick C; Grant, Barry J; Madura, Jeffry D

2012-07-03

Monoamine transporters (MATs) function by coupling ion gradients to the transport of dopamine, norepinephrine, or serotonin. Despite their importance in regulating neurotransmission, the exact conformational mechanism by which MATs function remains elusive. To this end, we have performed seven 250 ns accelerated molecular dynamics simulations of the leucine transporter, a model for neurotransmitter MATs. By varying the presence of binding-pocket leucine substrate and sodium ions, we have sampled plausible conformational states representative of the substrate transport cycle. The resulting trajectories were analyzed using principal component analysis of transmembrane helices 1b and 6a. This analysis revealed seven unique structures: two of the obtained conformations are similar to the currently published crystallographic structures, one conformation is similar to a proposed open inward structure, and four conformations represent novel structures of potential importance to the transport cycle. Further analysis reveals that the presence of binding-pocket sodium ions is necessary to stabilize the locked-occluded and open-inward conformations. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Service Mediation and Negotiation Bootstrapping as First Achievements Towards Self-adaptable Cloud Services

NASA Astrophysics Data System (ADS)

Brandic, Ivona; Music, Dejan; Dustdar, Schahram

Nowadays, novel computing paradigms as for example Cloud Computing are gaining more and more on importance. In case of Cloud Computing users pay for the usage of the computing power provided as a service. Beforehand they can negotiate specific functional and non-functional requirements relevant for the application execution. However, providing computing power as a service bears different research challenges. On one hand dynamic, versatile, and adaptable services are required, which can cope with system failures and environmental changes. On the other hand, human interaction with the system should be minimized. In this chapter we present the first results in establishing adaptable, versatile, and dynamic services considering negotiation bootstrapping and service mediation achieved in context of the Foundations of Self-Governing ICT Infrastructures (FoSII) project. We discuss novel meta-negotiation and SLA mapping solutions for Cloud services bridging the gap between current QoS models and Cloud middleware and representing important prerequisites for the establishment of autonomic Cloud services.

Kinetic modeling of particle dynamics in H- negative ion sources (invited)

NASA Astrophysics Data System (ADS)

Hatayama, A.; Shibata, T.; Nishioka, S.; Ohta, M.; Yasumoto, M.; Nishida, K.; Yamamoto, T.; Miyamoto, K.; Fukano, A.; Mizuno, T.

2014-02-01

Progress in the kinetic modeling of particle dynamics in H- negative ion source plasmas and their comparisons with experiments are reviewed, and discussed with some new results. Main focus is placed on the following two topics, which are important for the research and development of large negative ion sources and high power H- ion beams: (i) Effects of non-equilibrium features of EEDF (electron energy distribution function) on H- production, and (ii) extraction physics of H- ions and beam optics.

Actin filaments-A target for redox regulation.

PubMed

Wilson, Carlos; Terman, Jonathan R; González-Billault, Christian; Ahmed, Giasuddin

2016-10-01

Actin and its ability to polymerize into dynamic filaments is critical for the form and function of cells throughout the body. While multiple proteins have been characterized as affecting actin dynamics through noncovalent means, actin and its protein regulators are also susceptible to covalent modifications of their amino acid residues. In this regard, oxidation-reduction (Redox) intermediates have emerged as key modulators of the actin cytoskeleton with multiple different effects on cellular form and function. Here, we review work implicating Redox intermediates in post-translationally altering actin and discuss what is known regarding how these alterations affect the properties of actin. We also focus on two of the best characterized enzymatic sources of these Redox intermediates-the NADPH oxidase NOX and the flavoprotein monooxygenase MICAL-and detail how they have both been identified as altering actin, but share little similarity and employ different means to regulate actin dynamics. Finally, we discuss the role of these enzymes and redox signaling in regulating the actin cytoskeleton in vivo and highlight their importance for neuronal form and function in health and disease. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Large-scale Generation of Patterned Bubble Arrays on Printed Bi-functional Boiling Surfaces

NASA Astrophysics Data System (ADS)

Choi, Chang-Ho; David, Michele; Gao, Zhongwei; Chang, Alvin; Allen, Marshall; Wang, Hailei; Chang, Chih-Hung

2016-04-01

Bubble nucleation control, growth and departure dynamics is important in understanding boiling phenomena and enhancing nucleate boiling heat transfer performance. We report a novel bi-functional heterogeneous surface structure that is capable of tuning bubble nucleation, growth and departure dynamics. For the fabrication of the surface, hydrophobic polymer dot arrays are first printed on a substrate, followed by hydrophilic ZnO nanostructure deposition via microreactor-assisted nanomaterial deposition (MAND) processing. Wettability contrast between the hydrophobic polymer dot arrays and aqueous ZnO solution allows for the fabrication of heterogeneous surfaces with distinct wettability regions. Heterogeneous surfaces with various configurations were fabricated and their bubble dynamics were examined at elevated heat flux, revealing various nucleate boiling phenomena. In particular, aligned and patterned bubbles with a tunable departure frequency and diameter were demonstrated in a boiling experiment for the first time. Taking advantage of our fabrication method, a 6 inch wafer size heterogeneous surface was prepared. Pool boiling experiments were also performed to demonstrate a heat flux enhancement up to 3X at the same surface superheat using bi-functional surfaces, compared to a bare stainless steel surface.

Dynamic balance between master transcription factors determines the fates and functions of CD4 T cell and innate lymphoid cell subsets

PubMed Central

2017-01-01

CD4 T cells, including T regulatory cells (Treg cells) and effector T helper cells (Th cells), and recently identified innate lymphoid cells (ILCs) play important roles in host defense and inflammation. Both CD4 T cells and ILCs can be classified into distinct lineages based on their functions and the expression of lineage-specific genes, including those encoding effector cytokines, cell surface markers, and key transcription factors. It was first recognized that each lineage expresses a specific master transcription factor and the expression of these factors is mutually exclusive because of cross-regulation among these factors. However, recent studies indicate that the master regulators are often coexpressed. Furthermore, the expression of master regulators can be dynamic and quantitative. In this review, we will first discuss similarities and differences between the development and functions of CD4 T cell and ILC subsets and then summarize recent literature on quantitative, dynamic, and cell type–specific balance between the master transcription factors in determining heterogeneity and plasticity of these subsets. PMID:28630089

Actin filaments – a target for redox regulation

PubMed Central

Wilson, Carlos; Terman, Jonathan R.; González-Billault, Christian; Ahmed, Giasuddin

2016-01-01

Actin and its ability to polymerize into dynamic filaments is critical for the form and function of cells throughout the body. While multiple proteins have been characterized as affecting actin dynamics through non-covalent means, actin and its protein regulators are also susceptible to covalent modifications of their amino acid residues. In this regard, oxidation-reduction (Redox) intermediates have emerged as key modulators of the actin cytoskeleton with multiple different effects on cellular form and function. Here, we review work implicating Redox intermediates in post-translationally altering actin and discuss what is known regarding how these alterations affect the properties of actin. We also focus on two of the best characterized enzymatic sources of these Redox intermediates – the NADPH oxidase NOX and the flavoprotein monooxygenase MICAL – and detail how they have both been identified as altering actin, but share little similarity and employ different means to regulate actin dynamics. Finally, we discuss the role of these enzymes and redox signaling in regulating the actin cytoskeleton in vivo and highlight their importance for neuronal form and function in health and disease. PMID:27309342

Effects of Single Nucleotide Polymorphisms on Human N-Acetyltransferase 2 Structure and Dynamics by Molecular Dynamics Simulation

PubMed Central

Rajasekaran, M.; Abirami, Santhanam; Chen, Chinpan

2011-01-01

Background Arylamine N-acetyltransferase 2 (NAT2) is an important catalytic enzyme that metabolizes the carcinogenic arylamines, hydrazine drugs and chemicals. This enzyme is highly polymorphic in different human populations. Several polymorphisms of NAT2, including the single amino acid substitutions R64Q, I114T, D122N, L137F, Q145P, R197Q, and G286E, are classified as slow acetylators, whereas the wild-type NAT2 is classified as a fast acetylator. The slow acetylators are often associated with drug toxicity and efficacy as well as cancer susceptibility. The biological functions of these 7 mutations have previously been characterized, but the structural basis behind the reduced catalytic activity and reduced protein level is not clear. Methodology/Principal Findings We performed multiple molecular dynamics simulations of these mutants as well as NAT2 to investigate the structural and dynamical effects throughout the protein structure, specifically the catalytic triad, cofactor binding site, and the substrate binding pocket. None of these mutations induced unfolding; instead, their effects were confined to the inter-domain, domain 3 and 17-residue insert region, where the flexibility was significantly reduced relative to the wild-type. Structural effects of these mutations propagate through space and cause a change in catalytic triad conformation, cofactor binding site, substrate binding pocket size/shape and electrostatic potential. Conclusions/Significance Our results showed that the dynamical properties of all the mutant structures, especially in inter-domain, domain 3 and 17-residue insert region were affected in the same manner. Similarly, the electrostatic potential of all the mutants were altered and also the functionally important regions such as catalytic triad, cofactor binding site, and substrate binding pocket adopted different orientation and/or conformation relative to the wild-type that may affect the functions of the mutants. Overall, our study may provide the structural basis for reduced catalytic activity and protein level, as was experimentally observed for these polymorphisms. PMID:21980537

Effect of fullerenol surface chemistry on nanoparticle binding-induced protein misfolding

NASA Astrophysics Data System (ADS)

Radic, Slaven; Nedumpully-Govindan, Praveen; Chen, Ran; Salonen, Emppu; Brown, Jared M.; Ke, Pu Chun; Ding, Feng

2014-06-01

Fullerene and its derivatives with different surface chemistry have great potential in biomedical applications. Accordingly, it is important to delineate the impact of these carbon-based nanoparticles on protein structure, dynamics, and subsequently function. Here, we focused on the effect of hydroxylation -- a common strategy for solubilizing and functionalizing fullerene -- on protein-nanoparticle interactions using a model protein, ubiquitin. We applied a set of complementary computational modeling methods, including docking and molecular dynamics simulations with both explicit and implicit solvent, to illustrate the impact of hydroxylated fullerenes on the structure and dynamics of ubiquitin. We found that all derivatives bound to the model protein. Specifically, the more hydrophilic nanoparticles with a higher number of hydroxyl groups bound to the surface of the protein via hydrogen bonds, which stabilized the protein without inducing large conformational changes in the protein structure. In contrast, fullerene derivatives with a smaller number of hydroxyl groups buried their hydrophobic surface inside the protein, thereby causing protein denaturation. Overall, our results revealed a distinct role of surface chemistry on nanoparticle-protein binding and binding-induced protein misfolding.Fullerene and its derivatives with different surface chemistry have great potential in biomedical applications. Accordingly, it is important to delineate the impact of these carbon-based nanoparticles on protein structure, dynamics, and subsequently function. Here, we focused on the effect of hydroxylation -- a common strategy for solubilizing and functionalizing fullerene -- on protein-nanoparticle interactions using a model protein, ubiquitin. We applied a set of complementary computational modeling methods, including docking and molecular dynamics simulations with both explicit and implicit solvent, to illustrate the impact of hydroxylated fullerenes on the structure and dynamics of ubiquitin. We found that all derivatives bound to the model protein. Specifically, the more hydrophilic nanoparticles with a higher number of hydroxyl groups bound to the surface of the protein via hydrogen bonds, which stabilized the protein without inducing large conformational changes in the protein structure. In contrast, fullerene derivatives with a smaller number of hydroxyl groups buried their hydrophobic surface inside the protein, thereby causing protein denaturation. Overall, our results revealed a distinct role of surface chemistry on nanoparticle-protein binding and binding-induced protein misfolding. Electronic supplementary information (ESI) is available: Fluorescence spectra, ITC, CD spectra and other data as described in the text. See DOI: 10.1039/c4nr01544d

The role of loop ZA and Pro371 in the function of yeast Gcn5p bromodomain revealed through molecular dynamics and experiment.

PubMed

Pizzitutti, Francesco; Giansanti, Andrea; Ballario, Paola; Ornaghi, Prisca; Torreri, Paola; Ciccotti, Giovanni; Filetici, Patrizia

2006-01-01

Biological experiments were combined with molecular dynamics simulations to understand the importance of amino acidic residues present in the bromodomain of the yeast histone acetyltransferase Gcn5p. It was found that residue Pro371 plays an important role in the molecular recognition of the acetylated histone H4 tail by Gcn5p bromodomain. Crystallographic analysis of the complex showed that this residue does not directly interact with the histone substrate. It has been demonstrated that a double mutation Pro371Thr and Met372Ala in the Gcn5p bromodomain impairs chromatin remodeling activity. It is demonstrated here that, in this double mutant and in the fully deleted bromodomain strain, there is lower growth under amino acid deprivation conditions. By in vitro surface plasmon resonance (Biacore) experiments it is shown that the binding affinity of the double mutation to acetyl lysine 16 histone H4 peptide decreases. Molecular dynamics simulations were used to explain this loss in acetyl lysine-Gcn5p bromodomain affinity, in the double mutant. By comparing nanosecond molecular dynamics trajectories of the native as well as the single and doubly mutated bromodomain, it is concluded that the presence of Pro371 is important to the functionality of the Gcn5p bromodomain. In the simulation a point mutation involving this highly conserved residue induced an increase in the flexibility of the ZA loop, which in turn modulated the exposure of the binding pocket to the acetyl lysine. The combined double mutations (Pro371Thr-Met372Ala) not only markedly perturb the motion of the ZA loop but also destabilize the entire structure of the bromodomain. Copyright 2005 John Wiley & Sons, Ltd.

A Conserved Deubiquitinating Enzyme Uses Intrinsically Disordered Regions to Scaffold Multiple Protein Interaction Sites*

PubMed Central

Reed, Benjamin J.; Locke, Melissa N.; Gardner, Richard G.

2015-01-01

In the canonical view of protein function, it is generally accepted that the three-dimensional structure of a protein determines its function. However, the past decade has seen a dramatic growth in the identification of proteins with extensive intrinsically disordered regions (IDRs), which are conformationally plastic and do not appear to adopt single three-dimensional structures. One current paradigm for IDR function is that disorder enables IDRs to adopt multiple conformations, expanding the ability of a protein to interact with a wide variety of disparate proteins. The capacity for many interactions is an important feature of proteins that occupy the hubs of protein networks, in particular protein-modifying enzymes that usually have a broad spectrum of substrates. One such protein modification is ubiquitination, where ubiquitin is attached to proteins through ubiquitin ligases (E3s) and removed through deubiquitinating enzymes. Numerous proteomic studies have found that thousands of proteins are dynamically regulated by cycles of ubiquitination and deubiquitination. Thus, how these enzymes target their wide array of substrates is of considerable importance for understanding the function of the cell's diverse ubiquitination networks. Here, we characterize a yeast deubiquitinating enzyme, Ubp10, that possesses IDRs flanking its catalytic protease domain. We show that Ubp10 possesses multiple, distinct binding modules within its IDRs that are necessary and sufficient for directing protein interactions important for Ubp10's known roles in gene silencing and ribosome biogenesis. The human homolog of Ubp10, USP36, also has IDRs flanking its catalytic domain, and these IDRs similarly contain binding modules important for protein interactions. This work highlights the significant protein interaction scaffolding abilities of IDRs in the regulation of dynamic protein ubiquitination. PMID:26149687

Dynamic Granger causality based on Kalman filter for evaluation of functional network connectivity in fMRI data

PubMed Central

Havlicek, Martin; Jan, Jiri; Brazdil, Milan; Calhoun, Vince D.

2015-01-01

Increasing interest in understanding dynamic interactions of brain neural networks leads to formulation of sophisticated connectivity analysis methods. Recent studies have applied Granger causality based on standard multivariate autoregressive (MAR) modeling to assess the brain connectivity. Nevertheless, one important flaw of this commonly proposed method is that it requires the analyzed time series to be stationary, whereas such assumption is mostly violated due to the weakly nonstationary nature of functional magnetic resonance imaging (fMRI) time series. Therefore, we propose an approach to dynamic Granger causality in the frequency domain for evaluating functional network connectivity in fMRI data. The effectiveness and robustness of the dynamic approach was significantly improved by combining a forward and backward Kalman filter that improved estimates compared to the standard time-invariant MAR modeling. In our method, the functional networks were first detected by independent component analysis (ICA), a computational method for separating a multivariate signal into maximally independent components. Then the measure of Granger causality was evaluated using generalized partial directed coherence that is suitable for bivariate as well as multivariate data. Moreover, this metric provides identification of causal relation in frequency domain, which allows one to distinguish the frequency components related to the experimental paradigm. The procedure of evaluating Granger causality via dynamic MAR was demonstrated on simulated time series as well as on two sets of group fMRI data collected during an auditory sensorimotor (SM) or auditory oddball discrimination (AOD) tasks. Finally, a comparison with the results obtained from a standard time-invariant MAR model was provided. PMID:20561919

Selective host molecules obtained by dynamic adaptive chemistry.

PubMed

Matache, Mihaela; Bogdan, Elena; Hădade, Niculina D

2014-02-17

Up till 20 years ago, in order to endow molecules with function there were two mainstream lines of thought. One was to rationally design the positioning of chemical functionalities within candidate molecules, followed by an iterative synthesis-optimization process. The second was the use of a "brutal force" approach of combinatorial chemistry coupled with advanced screening for function. Although both methods provided important results, "rational design" often resulted in time-consuming efforts of modeling and synthesis only to find that the candidate molecule was not performing the designed job. "Combinatorial chemistry" suffered from a fundamental limitation related to the focusing of the libraries employed, often using lead compounds that limit its scope. Dynamic constitutional chemistry has developed as a combination of the two approaches above. Through the rational use of reversible chemical bonds together with a large plethora of precursor libraries, one is now able to build functional structures, ranging from quite simple molecules up to large polymeric structures. Thus, by introduction of the dynamic component within the molecular recognition processes, a new perspective of deciphering the world of the molecular events has aroused together with a new field of chemistry. Since its birth dynamic constitutional chemistry has continuously gained attention, in particular due to its ability to easily create from scratch outstanding molecular structures as well as the addition of adaptive features. The fundamental concepts defining the dynamic constitutional chemistry have been continuously extended to currently place it at the intersection between the supramolecular chemistry and newly defined adaptive chemistry, a pivotal feature towards evolutive chemistry. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The derivation and approximation of coarse-grained dynamics from Langevin dynamics

NASA Astrophysics Data System (ADS)

Ma, Lina; Li, Xiantao; Liu, Chun

2016-11-01

We present a derivation of a coarse-grained description, in the form of a generalized Langevin equation, from the Langevin dynamics model that describes the dynamics of bio-molecules. The focus is placed on the form of the memory kernel function, the colored noise, and the second fluctuation-dissipation theorem that connects them. Also presented is a hierarchy of approximations for the memory and random noise terms, using rational approximations in the Laplace domain. These approximations offer increasing accuracy. More importantly, they eliminate the need to evaluate the integral associated with the memory term at each time step. Direct sampling of the colored noise can also be avoided within this framework. Therefore, the numerical implementation of the generalized Langevin equation is much more efficient.

Liquid Aluminum: Atomic diffusion and viscosity from ab initio molecular dynamics

PubMed Central

Jakse, Noel; Pasturel, Alain

2013-01-01

We present a study of dynamic properties of liquid aluminum using density-functional theory within the local-density (LDA) and generalized gradient (GGA) approximations. We determine the temperature dependence of the self-diffusion coefficient as well the viscosity using direct methods. Comparisons with experimental data favor the LDA approximation to compute dynamic properties of liquid aluminum. We show that the GGA approximation induce more important backscattering effects due to an enhancement of the icosahedral short range order (ISRO) that impact directly dynamic properties like the self-diffusion coefficient. All these results are then used to test the Stokes-Einstein relation and the universal scaling law relating the diffusion coefficient and the excess entropy of a liquid. PMID:24190311

Mitochondrial Dynamics in Diabetes

PubMed Central

Galloway, Chad A.; Jhun, Bong Sook; Yu, Tianzheng

2011-01-01

Abstract Mitochondria are at the center of cellular energy metabolism and regulate cell life and death. The cell biological aspect of mitochondria, especially mitochondrial dynamics, has drawn much attention through implications in human pathology, including neurological disorders and metabolic diseases. Mitochondrial fission and fusion are the main processes governing the morphological plasticity and are controlled by multiple factors, including mechanochemical enzymes and accessory proteins. Emerging evidence suggests that mitochondrial dynamics plays an important role in metabolism–secretion coupling in pancreatic β-cells as well as complications of diabetes. This review describes an overview of mechanistic and functional aspects of mitochondrial fission and fusion, and comments on the recent advances connecting mitochondrial dynamics with diabetes and diabetic complications. Antioxid. Redox Signal. 14, 439–457. PMID:20518704

Bayesian Inference for Functional Dynamics Exploring in fMRI Data.

PubMed

Guo, Xuan; Liu, Bing; Chen, Le; Chen, Guantao; Pan, Yi; Zhang, Jing

2016-01-01

This paper aims to review state-of-the-art Bayesian-inference-based methods applied to functional magnetic resonance imaging (fMRI) data. Particularly, we focus on one specific long-standing challenge in the computational modeling of fMRI datasets: how to effectively explore typical functional interactions from fMRI time series and the corresponding boundaries of temporal segments. Bayesian inference is a method of statistical inference which has been shown to be a powerful tool to encode dependence relationships among the variables with uncertainty. Here we provide an introduction to a group of Bayesian-inference-based methods for fMRI data analysis, which were designed to detect magnitude or functional connectivity change points and to infer their functional interaction patterns based on corresponding temporal boundaries. We also provide a comparison of three popular Bayesian models, that is, Bayesian Magnitude Change Point Model (BMCPM), Bayesian Connectivity Change Point Model (BCCPM), and Dynamic Bayesian Variable Partition Model (DBVPM), and give a summary of their applications. We envision that more delicate Bayesian inference models will be emerging and play increasingly important roles in modeling brain functions in the years to come.

Synchrony, compensatory dynamics, and the functional trait basis of phenological diversity in a tropical dry forest tree community: effects of rainfall seasonality

NASA Astrophysics Data System (ADS)

Lasky, Jesse R.; Uriarte, María; Muscarella, Robert

2016-11-01

Interspecific variation in phenology is a key axis of functional diversity, potentially mediating how communities respond to climate change. The diverse drivers of phenology act across multiple temporal scales. For example, abiotic constraints favor synchronous reproduction (positive covariance among species), while biotic interactions can favor synchrony or compensatory dynamics (negative covariance). We used wavelet analyses to examine phenology of community flower and seed production for 45 tree species across multiple temporal scales in a tropical dry forest in Puerto Rico with marked rainfall seasonality. We asked three questions: (1) do species exhibit synchronous or compensatory temporal dynamics in reproduction, (2) do interspecific differences in phenology reflect variable responses to rainfall, and (3) is interspecific variation in phenology and response to a major drought associated with functional traits that mediate responses to moisture? Community-level flowering was synchronized at seasonal scales (˜5-6 mo) and at short scales (˜1 mo, following rainfall). However, seed rain exhibited significant compensatory dynamics at intraseasonal scales (˜3 mo), suggesting interspecific variation in temporal niches. Species with large leaves (associated with sensitivity to water deficit) peaked in reproduction synchronously with the peak of seasonal rainfall (˜5 mo scale). By contrast, species with high wood specific gravity (associated with drought resistance) tended to flower in drier periods. Flowering of tall species and those with large leaves was most tightly linked to intraseasonal (˜2 mo scale) rainfall fluctuations. Although the 2015 drought dramatically reduced community-wide reproduction, functional traits were not associated with the magnitude of species-specific declines. Our results suggest opposing drivers of synchronous versus compensatory dynamics at different temporal scales. Phenology associations with functional traits indicated that distinct strategies for coping with seasonality underlie phenological diversity. Observed drought responses highlight the importance of non-linear community responses to climate. Community phenology exhibits scale-specific patterns highlighting the need for multi-scale approaches to community dynamics.

THE DYNAMICS OF A NEUROMUSCULAR SYSTEM FUNCTIONAL CONDITION DURING THE PREPARATION FOR IMPORTANT CONTESTS

PubMed Central

Titov, G.

1973-01-01

The aim of this research was to determine a conjugation of the functional condition dynamics of the neuromuscular organs, visual analyser, latent period of the motorial activity and supporting kinosthetic functions at different stages of preparation of the sportsmen for important contests. The following research methods were used to achieve this aim: a functional mobility of the neuromuscular organs was determined with the help of an electrostimulation method (excitability thresholds, frequency range of optimum and maximum rhythm, data on the changes of a bioelectric potential in relation to electrical stimuli); a functional condition of the visual analyser was determined with the use of an electrostimulation method (excitability thresholds, frequency range of phosefan in the reaction to a threshold irritant); a grey matter neurodynamics was determined with the help of a chronoreflexometry using an audio irritant of a different power with the preliminary strain of motor centres or without it; supporting kinosthetic functions were determined with the help of seismotremography and stabilography (frequency and amplitude of tremor, deviations of the gravity centre of the body in different positions of the Romberg test). All the research on the systems mentioned was carried out within the preparatory, main and contest periods during the preparation for the important contests. Gymnasts, boxers and fencers were under observation. In all there were carried out 570 observations of 54 sportsmen of a high sporting qualification. The functional condition of the visual analyser at a satisfactory level of training was characterised by relatively low excitability thresholds and high frequency limits of phosefan. The functional mobility of the neuromuscular organs was reduced during this period. The supporting kinosthetic functions became apparent in the instability of frequency and amplitude tremor characteristics and general gravity centre deviations. The latent period of the motor movement reaction was the longest without the preliminary strain of the motor centres. The performance of intense training efforts was accompanied by distinct symptoms of the nervous system excitement against a background of the reduced functional mobility of the neuromuscular organs. Just before the main contests, when the sportsmen were in good training condition, the excitability thresholds of the visual analyser were slightly increasing; frequency limits of phosefan were falling; functional mobility of the neuromuscular organs achieved the highest value; supporting kinosthetic functions were characterised by stable values of the tremor frequency and amplitude and of the deviations of the general gravity centre of the body; minimum latent period of the motor movement reaction was dependent upon the preliminary strain of the motor centres. The data obtained gave us the opportunity to assume that the functional condition dynamics of the systems under consideration might characterise the level of an operative rest, as A. A. Ukhtomsky saw it, as a combatant readiness for physical activity.

Dynamic range of Nef-mediated evasion of HLA class II-restricted immune responses in early HIV-1 infection.

PubMed

Mahiti, Macdonald; Brumme, Zabrina L; Jessen, Heiko; Brockman, Mark A; Ueno, Takamasa

2015-07-31

HLA class II-restricted CD4(+) T lymphocytes play an important role in controlling HIV-1 replication, especially in the acute/early infection stage. But, HIV-1 Nef counteracts this immune response by down-regulating HLA-DR and up-regulating the invariant chain associated with immature HLA-II (Ii). Although functional heterogeneity of various Nef activities, including down-regulation of HLA class I (HLA-I), is well documented, our understanding of Nef-mediated evasion of HLA-II-restricted immune responses during acute/early infection remains limited. Here, we examined the ability of Nef clones from 47 subjects with acute/early progressive infection and 46 subjects with chronic progressive infection to up-regulate Ii and down-regulate HLA-DR and HLA-I from the surface of HIV-infected cells. HLA-I down-regulation function was preserved among acute/early Nef clones, whereas both HLA-DR down-regulation and Ii up-regulation functions displayed relatively broad dynamic ranges. Nef's ability to down-regulate HLA-DR and up-regulate Ii correlated positively at this stage, suggesting they are functionally linked in vivo. Acute/early Nef clones also exhibited higher HLA-DR down-regulation and lower Ii up-regulation functions compared to chronic Nef clones. Taken together, our results support enhanced Nef-mediated HLA class II immune evasion activities in acute/early compared to chronic infection, highlighting the potential importance of these functions following transmission. Copyright © 2015 Elsevier Inc. All rights reserved.

Dynamic correlations in the highly dilute 2D electron liquid: Loss function, critical wave vector and analytic plasmon dispersion

NASA Astrophysics Data System (ADS)

Drachta, Jürgen T.; Kreil, Dominik; Hobbiger, Raphael; Böhm, Helga M.

2018-03-01

Correlations, highly important in low-dimensional systems, are known to decrease the plasmon dispersion of two-dimensional electron liquids. Here we calculate the plasmon properties, applying the 'Dynamic Many-Body Theory', accounting for correlated two-particle-two-hole fluctuations. These dynamic correlations are found to significantly lower the plasmon's energy. For the data obtained numerically, we provide an analytic expression that is valid across a wide range both of densities and of wave vectors. Finally, we demonstrate how this can be invoked in determining the actual electron densities from measurements on an AlGaAs quantum well.

Structural dynamics of the mitochondrial compartment.

PubMed

Thorsness, P E

1992-09-01

The metabolic activities of mitochondria have been extensively characterized. However, there is much less known about the morphogenic changes of the mitochondrial compartment during growth, development and aging of the cell and the consequences of those structural changes on cellular metabolism. There is a growing body of evidence for interactions of mitochondria with cytoskeletal components and changes of mitochondrial structure during development and in response to changing environmental conditions. Segregation and recombination of mitochondrial genomes are also processes dependent upon the dynamic nature of the mitochondrial compartment. These regulatory and structural aspects of mitochondrial compartment dynamics will play an important role in the analysis of mitochondrial function and pathology.

Dynamic rheological properties of dough as affected by amylases from various sources.

PubMed

Doğan, Ismail S

2002-12-01

The effect of alpha-amylases from cereal, fungal, and bacterial sources on dough dynamic rheological properties was investigated. Dynamic rheological study of flour-and-water doughs during resting period showed significant changes in dough rheological properties as a function of alpha-amylases. Addition of alpha-amylases caused a time-dependent decrease in G', storage modulus. The enzyme action on starch during baking increased viscous flow properties. These changes were temperature-dependent. The thermal inactivation temperature of alpha-amylase plays an important role in modification of starch. Rheological changes in dough will alter the machinability of the dough and the quality of end products.

Scale-Free Neural and Physiological Dynamics in Naturalistic Stimuli Processing

PubMed Central

Lin, Amy

2016-01-01

Abstract Neural activity recorded at multiple spatiotemporal scales is dominated by arrhythmic fluctuations without a characteristic temporal periodicity. Such activity often exhibits a 1/f-type power spectrum, in which power falls off with increasing frequency following a power-law function: P(f)∝1/fβ, which is indicative of scale-free dynamics. Two extensively studied forms of scale-free neural dynamics in the human brain are slow cortical potentials (SCPs)—the low-frequency (<5 Hz) component of brain field potentials—and the amplitude fluctuations of α oscillations, both of which have been shown to carry important functional roles. In addition, scale-free dynamics characterize normal human physiology such as heartbeat dynamics. However, the exact relationships among these scale-free neural and physiological dynamics remain unclear. We recorded simultaneous magnetoencephalography and electrocardiography in healthy subjects in the resting state and while performing a discrimination task on scale-free dynamical auditory stimuli that followed different scale-free statistics. We observed that long-range temporal correlation (captured by the power-law exponent β) in SCPs positively correlated with that of heartbeat dynamics across time within an individual and negatively correlated with that of α-amplitude fluctuations across individuals. In addition, across individuals, long-range temporal correlation of both SCP and α-oscillation amplitude predicted subjects’ discrimination performance in the auditory task, albeit through antagonistic relationships. These findings reveal interrelations among different scale-free neural and physiological dynamics and initial evidence for the involvement of scale-free neural dynamics in the processing of natural stimuli, which often exhibit scale-free dynamics. PMID:27822495

Which Brain Regions are Important for Seizure Dynamics in Epileptic Networks? Influence of Link Identification and EEG Recording Montage on Node Centralities.

PubMed

Geier, Christian; Lehnertz, Klaus

2017-02-01

Nodes in large-scale epileptic networks that are crucial for seizure facilitation and termination can be regarded as potential targets for individualized focal therapies. Graph-theoretical approaches based on centrality concepts can help to identify such important nodes, however, they may be influenced by the way networks are derived from empirical data. Here we investigate evolving functional epileptic brain networks during 82 focal seizures with different anatomical onset locations that we derive from multichannel intracranial electroencephalographic recordings from 51 patients. We demonstrate how the various methodological steps (from the recording montage via node and link inference to the assessment of node centralities) affect importance estimation and discuss their impact on the interpretability of findings in the context of pathophysiological aspects of seizure dynamics.

From protein sequence to dynamics and disorder with DynaMine.

PubMed

Cilia, Elisa; Pancsa, Rita; Tompa, Peter; Lenaerts, Tom; Vranken, Wim F

2013-01-01

Protein function and dynamics are closely related; however, accurate dynamics information is difficult to obtain. Here based on a carefully assembled data set derived from experimental data for proteins in solution, we quantify backbone dynamics properties on the amino-acid level and develop DynaMine--a fast, high-quality predictor of protein backbone dynamics. DynaMine uses only protein sequence information as input and shows great potential in distinguishing regions of different structural organization, such as folded domains, disordered linkers, molten globules and pre-structured binding motifs of different sizes. It also identifies disordered regions within proteins with an accuracy comparable to the most sophisticated existing predictors, without depending on prior disorder knowledge or three-dimensional structural information. DynaMine provides molecular biologists with an important new method that grasps the dynamical characteristics of any protein of interest, as we show here for human p53 and E1A from human adenovirus 5.

GPCRs: What Can We Learn from Molecular Dynamics Simulations?

PubMed

Velgy, Naushad; Hedger, George; Biggin, Philip C

2018-01-01

Advances in the structural biology of G-protein Coupled Receptors have resulted in a significant step forward in our understanding of how this important class of drug targets function at the molecular level. However, it has also become apparent that they are very dynamic molecules, and moreover, that the underlying dynamics is crucial in shaping the response to different ligands. Molecular dynamics simulations can provide unique insight into the dynamic properties of GPCRs in a way that is complementary to many experimental approaches. In this chapter, we describe progress in three distinct areas that are particularly difficult to study with other techniques: atomic level investigation of the conformational changes that occur when moving between the various states that GPCRs can exist in, the pathways that ligands adopt during binding/unbinding events and finally, the influence of lipids on the conformational dynamics of GPCRs.

Dynamers: Polyacylhydrazone reversible covalent polymers, component exchange, and constitutional diversity

PubMed Central

Skene, Williams G.; Lehn, Jean-Marie P.

2004-01-01

Component exchange in reversible polymers allows the generation of dynamic constitutional diversity. The polycondensation of dihydrazides with dialdehydes generates polyacylhydrazones, to which the acylhydrazone functionality formed confers both hydrogen-bonding and reversibility features through the amide and imine groups, respectively. Polyacylhydrazones are thus dynamic polyamides. They are able to reversibly exchange either one or both of their repeating monomer units in the presence of different monomers, thus presenting constitutional dynamic diversity. The polymers subjected to monomer exchange/interchange may be brought to exhibit physical properties vastly different from those of the original polymer. The principle may be extended to other important classes of polymers, giving access, for instance, to dynamic polyureas or polycarbamates. These reversible polymers are therefore able to incorporate, decorporate, or reshuffle their constituting monomers, namely in response to environmental physical or chemical factors, an adaptability feature central to constitutional dynamic chemistry. PMID:15150411

Trait-mediated assembly processes predict successional changes in community diversity of tropical forests.

PubMed

Lasky, Jesse R; Uriarte, María; Boukili, Vanessa K; Chazdon, Robin L

2014-04-15

Interspecific differences in relative fitness can cause local dominance by a single species. However, stabilizing interspecific niche differences can promote local diversity. Understanding these mechanisms requires that we simultaneously quantify their effects on demography and link these effects to community dynamics. Successional forests are ideal systems for testing assembly theory because they exhibit rapid community assembly. Here, we leverage functional trait and long-term demographic data to build spatially explicit models of successional community dynamics of lowland rainforests in Costa Rica. First, we ask what the effects and relative importance of four trait-mediated community assembly processes are on tree survival, a major component of fitness. We model trait correlations with relative fitness differences that are both density-independent and -dependent in addition to trait correlations with stabilizing niche differences. Second, we ask how the relative importance of these trait-mediated processes relates to successional changes in functional diversity. Tree dynamics were more strongly influenced by trait-related interspecific variation in average survival than trait-related responses to neighbors, with wood specific gravity (WSG) positively correlated with greater survival. Our findings also suggest that competition was mediated by stabilizing niche differences associated with specific leaf area (SLA) and leaf dry matter content (LDMC). These drivers of individual-level survival were reflected in successional shifts to higher SLA and LDMC diversity but lower WSG diversity. Our study makes significant advances to identifying the links between individual tree performance, species functional traits, and mechanisms of tropical forest succession.

Monomer–dimer dynamics and distribution of GPI-anchored uPAR are determined by cell surface protein assemblies

PubMed Central

Caiolfa, Valeria R.; Zamai, Moreno; Malengo, Gabriele; Andolfo, Annapaola; Madsen, Chris D.; Sutin, Jason; Digman, Michelle A.; Gratton, Enrico; Blasi, Francesco; Sidenius, Nicolai

2007-01-01

To search for functional links between glycosylphosphatidylinositol (GPI) protein monomer–oligomer exchange and membrane dynamics and confinement, we studied urokinase plasminogen activator (uPA) receptor (uPAR), a GPI receptor involved in the regulation of cell adhesion, migration, and proliferation. Using a functionally active fluorescent protein–uPAR in live cells, we analyzed the effect that extracellular matrix proteins and uPAR ligands have on uPAR dynamics and dimerization at the cell membrane. Vitronectin directs the recruitment of dimers and slows down the diffusion of the receptors at the basal membrane. The commitment to uPA–plasminogen activator inhibitor type 1–mediated endocytosis and recycling modifies uPAR diffusion and induces an exchange between uPAR monomers and dimers. This exchange is fully reversible. The data demonstrate that cell surface protein assemblies are important in regulating the dynamics and localization of uPAR at the cell membrane and the exchange of monomers and dimers. These results also provide a strong rationale for dynamic studies of GPI-anchored molecules in live cells at steady state and in the absence of cross-linker/clustering agents. PMID:18056417

A time-correlation function approach to nuclear dynamical effects in X-ray spectroscopy

NASA Astrophysics Data System (ADS)

Karsten, Sven; Bokarev, Sergey I.; Aziz, Saadullah G.; Ivanov, Sergei D.; Kühn, Oliver

2017-06-01

Modern X-ray spectroscopy has proven itself as a robust tool for probing the electronic structure of atoms in complex environments. Despite working on energy scales that are much larger than those corresponding to nuclear motions, taking nuclear dynamics and the associated nuclear correlations into account may be of importance for X-ray spectroscopy. Recently, we have developed an efficient protocol to account for nuclear dynamics in X-ray absorption and resonant inelastic X-ray scattering spectra [Karsten et al., J. Phys. Chem. Lett. 8, 992 (2017)], based on ground state molecular dynamics accompanied with state-of-the-art calculations of electronic excitation energies and transition dipoles. Here, we present an alternative derivation of the formalism and elaborate on the developed simulation protocol using gas phase and bulk water as examples. The specific spectroscopic features stemming from the nuclear motions are analyzed and traced down to the dynamics of electronic energy gaps and transition dipole correlation functions. The observed tendencies are explained on the basis of a simple harmonic model, and the involved approximations are discussed. The method represents a step forward over the conventional approaches that treat the system in full complexity and provides a reasonable starting point for further improvements.

A time-correlation function approach to nuclear dynamical effects in X-ray spectroscopy.

PubMed

Karsten, Sven; Bokarev, Sergey I; Aziz, Saadullah G; Ivanov, Sergei D; Kühn, Oliver

2017-06-14

Modern X-ray spectroscopy has proven itself as a robust tool for probing the electronic structure of atoms in complex environments. Despite working on energy scales that are much larger than those corresponding to nuclear motions, taking nuclear dynamics and the associated nuclear correlations into account may be of importance for X-ray spectroscopy. Recently, we have developed an efficient protocol to account for nuclear dynamics in X-ray absorption and resonant inelastic X-ray scattering spectra [Karsten et al., J. Phys. Chem. Lett. 8, 992 (2017)], based on ground state molecular dynamics accompanied with state-of-the-art calculations of electronic excitation energies and transition dipoles. Here, we present an alternative derivation of the formalism and elaborate on the developed simulation protocol using gas phase and bulk water as examples. The specific spectroscopic features stemming from the nuclear motions are analyzed and traced down to the dynamics of electronic energy gaps and transition dipole correlation functions. The observed tendencies are explained on the basis of a simple harmonic model, and the involved approximations are discussed. The method represents a step forward over the conventional approaches that treat the system in full complexity and provides a reasonable starting point for further improvements.

Surface and finite size effect on fluctuations dynamics in nanoparticles with long-range order

NASA Astrophysics Data System (ADS)

Morozovska, A. N.; Eliseev, E. A.

2010-02-01

The influence of surface and finite size on the dynamics of the order parameter fluctuations and critical phenomena in the three-dimensional (3D)-confined systems with long-range order was not considered theoretically. In this paper, we study the influence of surface and finite size on the dynamics of the order parameter fluctuations in the particles of arbitrary shape. We consider concrete examples of the spherical and cylindrical ferroic nanoparticles within Landau-Ginzburg-Devonshire phenomenological approach. Allowing for the strong surface energy contribution in micro and nanoparticles, the analytical expressions derived for the Ornstein-Zernike correlator of the long-range order parameter spatial-temporal fluctuations, dynamic generalized susceptibility, relaxation times, and correlation radii discrete spectra are different from those known for bulk systems. Obtained analytical expressions for the correlation function of the order parameter spatial-temporal fluctuations in micro and nanosized systems can be useful for the quantitative analysis of the dynamical structural factors determined from magnetic resonance diffraction and scattering spectra. Besides the practical importance of the correlation function for the analysis of the experimental data, derived expressions for the fluctuations strength determine the fundamental limits of phenomenological theories applicability for 3D-confined systems.

Thermostability of In Vitro Evolved Bacillus subtilis Lipase A: A Network and Dynamics Perspective

PubMed Central

Srivastava, Ashutosh; Sinha, Somdatta

2014-01-01

Proteins in thermophilic organisms remain stable and function optimally at high temperatures. Owing to their important applicability in many industrial processes, such thermostable proteins have been studied extensively, and several structural factors attributed to their enhanced stability. How these factors render the emergent property of thermostability to proteins, even in situations where no significant changes occur in their three-dimensional structures in comparison to their mesophilic counter-parts, has remained an intriguing question. In this study we treat Lipase A from Bacillus subtilis and its six thermostable mutants in a unified manner and address the problem with a combined complex network-based analysis and molecular dynamic studies to find commonality in their properties. The Protein Contact Networks (PCN) of the wild-type and six mutant Lipase A structures developed at a mesoscopic scale were analyzed at global network and local node (residue) level using network parameters and community structure analysis. The comparative PCN analysis of all proteins pointed towards important role of specific residues in the enhanced thermostability. Network analysis results were corroborated with finer-scale molecular dynamics simulations at both room and high temperatures. Our results show that this combined approach at two scales can uncover small but important changes in the local conformations that add up to stabilize the protein structure in thermostable mutants, even when overall conformation differences among them are negligible. Our analysis not only supports the experimentally determined stabilizing factors, but also unveils the important role of contacts, distributed throughout the protein, that lead to thermostability. We propose that this combined mesoscopic-network and fine-grained molecular dynamics approach is a convenient and useful scheme not only to study allosteric changes leading to protein stability in the face of negligible over-all conformational changes due to mutations, but also in other molecular networks where change in function does not accompany significant change in the network structure. PMID:25122499

Habitat structure mediates biodiversity effects on ecosystem properties

PubMed Central

Godbold, J. A.; Bulling, M. T.; Solan, M.

2011-01-01

Much of what we know about the role of biodiversity in mediating ecosystem processes and function stems from manipulative experiments, which have largely been performed in isolated, homogeneous environments that do not incorporate habitat structure or allow natural community dynamics to develop. Here, we use a range of habitat configurations in a model marine benthic system to investigate the effects of species composition, resource heterogeneity and patch connectivity on ecosystem properties at both the patch (bioturbation intensity) and multi-patch (nutrient concentration) scale. We show that allowing fauna to move and preferentially select patches alters local species composition and density distributions, which has negative effects on ecosystem processes (bioturbation intensity) at the patch scale, but overall positive effects on ecosystem functioning (nutrient concentration) at the multi-patch scale. Our findings provide important evidence that community dynamics alter in response to localized resource heterogeneity and that these small-scale variations in habitat structure influence species contributions to ecosystem properties at larger scales. We conclude that habitat complexity forms an important buffer against disturbance and that contemporary estimates of the level of biodiversity required for maintaining future multi-functional systems may need to be revised. PMID:21227969

Habitat structure mediates biodiversity effects on ecosystem properties.

PubMed

Godbold, J A; Bulling, M T; Solan, M

2011-08-22

Much of what we know about the role of biodiversity in mediating ecosystem processes and function stems from manipulative experiments, which have largely been performed in isolated, homogeneous environments that do not incorporate habitat structure or allow natural community dynamics to develop. Here, we use a range of habitat configurations in a model marine benthic system to investigate the effects of species composition, resource heterogeneity and patch connectivity on ecosystem properties at both the patch (bioturbation intensity) and multi-patch (nutrient concentration) scale. We show that allowing fauna to move and preferentially select patches alters local species composition and density distributions, which has negative effects on ecosystem processes (bioturbation intensity) at the patch scale, but overall positive effects on ecosystem functioning (nutrient concentration) at the multi-patch scale. Our findings provide important evidence that community dynamics alter in response to localized resource heterogeneity and that these small-scale variations in habitat structure influence species contributions to ecosystem properties at larger scales. We conclude that habitat complexity forms an important buffer against disturbance and that contemporary estimates of the level of biodiversity required for maintaining future multi-functional systems may need to be revised.

Measuring and comparing structural fluctuation patterns in large protein datasets.

PubMed

Fuglebakk, Edvin; Echave, Julián; Reuter, Nathalie

2012-10-01

The function of a protein depends not only on its structure but also on its dynamics. This is at the basis of a large body of experimental and theoretical work on protein dynamics. Further insight into the dynamics-function relationship can be gained by studying the evolutionary divergence of protein motions. To investigate this, we need appropriate comparative dynamics methods. The most used dynamical similarity score is the correlation between the root mean square fluctuations (RMSF) of aligned residues. Despite its usefulness, RMSF is in general less evolutionarily conserved than the native structure. A fundamental issue is whether RMSF is not as conserved as structure because dynamics is less conserved or because RMSF is not the best property to use to study its conservation. We performed a systematic assessment of several scores that quantify the (dis)similarity between protein fluctuation patterns. We show that the best scores perform as well as or better than structural dissimilarity, as assessed by their consistency with the SCOP classification. We conclude that to uncover the full extent of the evolutionary conservation of protein fluctuation patterns, it is important to measure the directions of fluctuations and their correlations between sites. Nathalie.Reuter@mbi.uib.no Supplementary data are available at Bioinformatics Online.

Toward a Dynamically Reconfigurable Computing and Communication System for Small Spacecraft

NASA Technical Reports Server (NTRS)

Kifle, Muli; Andro, Monty; Tran, Quang K.; Fujikawa, Gene; Chu, Pong P.

2003-01-01

Future science missions will require the use of multiple spacecraft with multiple sensor nodes autonomously responding and adapting to a dynamically changing space environment. The acquisition of random scientific events will require rapidly changing network topologies, distributed processing power, and a dynamic resource management strategy. Optimum utilization and configuration of spacecraft communications and navigation resources will be critical in meeting the demand of these stringent mission requirements. There are two important trends to follow with respect to NASA's (National Aeronautics and Space Administration) future scientific missions: the use of multiple satellite systems and the development of an integrated space communications network. Reconfigurable computing and communication systems may enable versatile adaptation of a spacecraft system's resources by dynamic allocation of the processor hardware to perform new operations or to maintain functionality due to malfunctions or hardware faults. Advancements in FPGA (Field Programmable Gate Array) technology make it possible to incorporate major communication and network functionalities in FPGA chips and provide the basis for a dynamically reconfigurable communication system. Advantages of higher computation speeds and accuracy are envisioned with tremendous hardware flexibility to ensure maximum survivability of future science mission spacecraft. This paper discusses the requirements, enabling technologies, and challenges associated with dynamically reconfigurable space communications systems.

Effects of aging in catastrophe on the steady state and dynamics of a microtubule population

NASA Astrophysics Data System (ADS)

Jemseena, V.; Gopalakrishnan, Manoj

2015-05-01

Several independent observations have suggested that the catastrophe transition in microtubules is not a first-order process, as is usually assumed. Recent in vitro observations by Gardner et al. [M. K. Gardner et al., Cell 147, 1092 (2011), 10.1016/j.cell.2011.10.037] showed that microtubule catastrophe takes place via multiple steps and the frequency increases with the age of the filament. Here we investigate, via numerical simulations and mathematical calculations, some of the consequences of the age dependence of catastrophe on the dynamics of microtubules as a function of the aging rate, for two different models of aging: exponential growth, but saturating asymptotically, and purely linear growth. The boundary demarcating the steady-state and non-steady-state regimes in the dynamics is derived analytically in both cases. Numerical simulations, supported by analytical calculations in the linear model, show that aging leads to nonexponential length distributions in steady state. More importantly, oscillations ensue in microtubule length and velocity. The regularity of oscillations, as characterized by the negative dip in the autocorrelation function, is reduced by increasing the frequency of rescue events. Our study shows that the age dependence of catastrophe could function as an intrinsic mechanism to generate oscillatory dynamics in a microtubule population, distinct from hitherto identified ones.

Fluctuations When Driving Between Nonequilibrium Steady States

NASA Astrophysics Data System (ADS)

Riechers, Paul M.; Crutchfield, James P.

2017-08-01

Maintained by environmental fluxes, biological systems are thermodynamic processes that operate far from equilibrium without detailed-balanced dynamics. Yet, they often exhibit well defined nonequilibrium steady states (NESSs). More importantly, critical thermodynamic functionality arises directly from transitions among their NESSs, driven by environmental switching. Here, we identify the constraints on excess heat and dissipated work necessary to control a system that is kept far from equilibrium by background, uncontrolled "housekeeping" forces. We do this by extending the Crooks fluctuation theorem to transitions among NESSs, without invoking an unphysical dual dynamics. This and corresponding integral fluctuation theorems determine how much work must be expended when controlling systems maintained far from equilibrium. This generalizes thermodynamic feedback control theory, showing that Maxwellian Demons can leverage mesoscopic-state information to take advantage of the excess energetics in NESS transitions. We also generalize an approach recently used to determine the work dissipated when driving between functionally relevant configurations of an active energy-consuming complex system. Altogether, these results highlight universal thermodynamic laws that apply to the accessible degrees of freedom within the effective dynamic at any emergent level of hierarchical organization. By way of illustration, we analyze a voltage-gated sodium ion channel whose molecular conformational dynamics play a critical functional role in propagating action potentials in mammalian neuronal membranes.

Brownian dynamics without Green's functions

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

Delong, Steven; Donev, Aleksandar, E-mail: donev@courant.nyu.edu; Usabiaga, Florencio Balboa

2014-04-07

We develop a Fluctuating Immersed Boundary (FIB) method for performing Brownian dynamics simulations of confined particle suspensions. Unlike traditional methods which employ analytical Green's functions for Stokes flow in the confined geometry, the FIB method uses a fluctuating finite-volume Stokes solver to generate the action of the response functions “on the fly.” Importantly, we demonstrate that both the deterministic terms necessary to capture the hydrodynamic interactions among the suspended particles, as well as the stochastic terms necessary to generate the hydrodynamically correlated Brownian motion, can be generated by solving the steady Stokes equations numerically only once per time step. Thismore » is accomplished by including a stochastic contribution to the stress tensor in the fluid equations consistent with fluctuating hydrodynamics. We develop novel temporal integrators that account for the multiplicative nature of the noise in the equations of Brownian dynamics and the strong dependence of the mobility on the configuration for confined systems. Notably, we propose a random finite difference approach to approximating the stochastic drift proportional to the divergence of the configuration-dependent mobility matrix. Through comparisons with analytical and existing computational results, we numerically demonstrate the ability of the FIB method to accurately capture both the static (equilibrium) and dynamic properties of interacting particles in flow.« less

Human Maternal Brain Plasticity: Adaptation to Parenting

ERIC Educational Resources Information Center

Kim, Pilyoung

2016-01-01

New mothers undergo dynamic neural changes that support positive adaptation to parenting and the development of mother-infant relationships. In this article, I review important psychological adaptations that mothers experience during pregnancy and the early postpartum period. I then review evidence of structural and functional plasticity in human…

Endoplasmic Reticulum and the Unfolded Protein Response: Dynamics and Metabolic Integration

PubMed Central

Bravo, Roberto; Parra, Valentina; Gatica, Damián; Rodriguez, Andrea E.; Torrealba, Natalia; Paredes, Felipe; Wang, Zhao V.; Zorzano, Antonio; Hill, Joseph A.; Jaimovich, Enrique; Quest, Andrew F.G.; Lavandero, Sergio

2013-01-01

The endoplasmic reticulum (ER) is a dynamic intracellular organelle with multiple functions essential for cellular homeostasis, development, and stress responsiveness. In response to cellular stress, a well-established signaling cascade, the unfolded protein response (UPR), is activated. This intricate mechanism is an important means of reestablishing cellular homeostasis and alleviating the inciting stress. Now, emerging evidence has demonstrated that the UPR influences cellular metabolism through diverse mechanisms, including calcium and lipid transfer, raising the prospect of involvement of these processes in the pathogenesis of disease, including neurodegeneration, cancer, diabetes mellitus and cardiovascular disease. Here, we review the distinct functions of the ER and UPR from a metabolic point of view, highlighting their association with prevalent pathologies. PMID:23317820

Ab-Initio Molecular Dynamics Simulation of Graphene Sheet

NASA Astrophysics Data System (ADS)

Kolev, S.; Balchev, I.; Cvetkov, K.; Tinchev, S.; Milenov, T.

2017-01-01

The study of graphene is important because it is a promising material for a variety of applications in the electronic industry. In the present work, the properties of а 2D periodic graphene sheet are studied with the use of ab initio molecular dynamics. DFT in the generalized gradient approximation is used in order to carry out the dynamical simulations. The PBE functional and DZVP-MOLOPT basis set are implemented in the CP2K/Quickstep package. A periodic box, consisting of 288 carbon atoms is chosen for the simulations. After geometry optimization it has dimensions 2964 x 2964 x 1500 pm and form angles of 90, 90, 60 degrees. The dynamical simulation is run for 1 ps in the NPT ensemble, at temperature T = 298.15 K. The radial distribution function shows a first peak at 142 pm, marking the bond length between carbon atoms. The density of states for the periodic systems is simulated as occupied orbitals represent the valence band and unoccupied ones the conduction band. The calculated bandgap, as expected is close to 0 eV.

Viscoelastic properties of rabbit vocal folds after augmentation.

PubMed

Hertegård, Stellan; Dahlqvist, Ake; Laurent, Claude; Borzacchiello, Assunta; Ambrosio, Luigi

2003-03-01

Vocal fold function is closely related to tissue viscoelasticity. Augmentation substances may alter the viscoelastic properties of vocal fold tissues and hence their vibratory capacity. We sought to investigate the viscoelastic properties of rabbit vocal folds in vitro after injections of various augmentation substances. Polytetrafluoroethylene (Teflon), cross-linked collagen (Zyplast), and cross-linked hyaluronan, hylan b gel (Hylaform) were injected into the lamina propria and the thyroarytenoid muscle of rabbit vocal folds. Dynamic viscosity of the injected vocal fold as a function of frequency was measured with a Bohlin parallel-plate rheometer during small-amplitude oscillation. All injected vocal folds showed a decreasing dynamic viscosity with increasing frequency. Vocal fold samples injected with hylan b gel showed the lowest dynamic viscosity, quite close to noninjected control samples. Vocal folds injected with polytetrafluoroethylene showed the highest dynamic viscosity followed by the collagen samples. The data indicated that hylan b gel in short-term renders the most natural viscoelastic properties to the vocal fold among the substances tested. This is of importance to restore/preserve the vibratory capacity of the vocal folds when glottal insufficiency is treated with injections.

GAIT DYNAMICS, FRACTALS AND FALLS: FINDING MEANING IN THE STRIDE-TO-STRIDE FLUCTUATIONS OF HUMAN WALKING

PubMed Central

Hausdorff, Jeffrey M

2007-01-01

Until recently, quantitative studies of walking have typically focused on properties of a typical or average stride, ignoring the stride-to-stride fluctuations and considering these fluctuations to be noise. Work over the past two decades has demonstrated, however, that the alleged noise actually conveys important information. The magnitude of the stride-to-stride fluctuations and their changes over time during a walk – gait dynamics – may be useful in understanding the physiology of gait, in quantifying age-related and pathologic alterations in the locomotor control system, and in augmenting objective measurement of mobility and functional status Indeed, alterations in gait dynamics may help to determine disease severity, medication utility, and fall risk, and to objectively document improvements in response to therapeutic interventions, above and beyond what can be gleaned from measures based on the average, typical stride. This review discusses support for the idea that gait dynamics has meaning and may be useful in providing insight into the neural control of locomtion and for enhancing functional assessment of aging, chronic disease, and their impact on mobility. PMID:17618701

Ab initio molecular dynamics simulation of LiBr association in water

NASA Astrophysics Data System (ADS)

Izvekov, Sergei; Philpott, Michael R.

2000-12-01

A computationally economical scheme which unifies the density functional description of an ionic solute and the classical description of a solvent was developed. The density functional part of the scheme comprises Car-Parrinello and related formalisms. The substantial saving in the computer time is achieved by performing the ab initio molecular dynamics of the solute electronic structure in a relatively small basis set constructed from lowest energy Kohn-Sham orbitals calculated for a single anion in vacuum, instead of using plane wave basis. The methodology permits simulation of an ionic solution for longer time scales while keeping accuracy in the prediction of the solute electronic structure. As an example the association of the Li+-Br- ion-pair system in water is studied. The results of the combined molecular dynamics simulation are compared with that obtained from the classical simulation with ion-ion interaction described by the pair potential of Born-Huggins-Mayer type. The comparison reveals an important role played by the polarization of the Br- ion in the dynamics of ion pair association.

Oligopolies with contingent workforce and unemployment insurance systems

NASA Astrophysics Data System (ADS)

Matsumoto, Akio; Merlone, Ugo; Szidarovszky, Ferenc

2015-10-01

In the recent literature the introduction of modified cost functions has added reality into the classical oligopoly analysis. Furthermore, the market evolution requires much more flexibility to firms, and in several countries contingent workforce plays an important role in the production choices by the firms. Therefore, an analysis of dynamic adjustment costs is in order to understand oligopoly dynamics. In this paper, dynamic single-product oligopolies without product differentiation are first examined with the additional consideration of production adjustment costs. Linear inverse demand and cost functions are considered and it is assumed that the firms adjust their outputs partially toward best response. The set of the steady states is characterized by a system of linear inequalities and there are usually infinitely many steady states. The asymptotic behavior of the output trajectories is examined by using computer simulation. The numerical results indicate that the resulting dynamics is richer than in the case of the classical Cournot model. This model and results are then compared to oligopolies with unemployment insurance systems when the additional cost is considered if firms do not use their maximum capacities.

Data collapse and critical dynamics in neuronal avalanche data

NASA Astrophysics Data System (ADS)

Butler, Thomas; Friedman, Nir; Dahmen, Karin; Beggs, John; Deville, Lee; Ito, Shinya

2012-02-01

The tasks of information processing, computation, and response to stimuli require neural computation to be remarkably flexible and diverse. To optimally satisfy the demands of neural computation, neuronal networks have been hypothesized to operate near a non-equilibrium critical point. In spite of their importance for neural dynamics, experimental evidence for critical dynamics has been primarily limited to power law statistics that can also emerge from non-critical mechanisms. By tracking the firing of large numbers of synaptically connected cortical neurons and comparing the resulting data to the predictions of critical phenomena, we show that cortical tissues in vitro can function near criticality. Among the most striking predictions of critical dynamics is that the mean temporal profiles of avalanches of widely varying durations are quantitatively described by a single universal scaling function (data collapse). We show for the first time that this prediction is confirmed in neuronal networks. We also show that the data have three additional features predicted by critical phenomena: approximate power law distributions of avalanche sizes and durations, samples in subcritical and supercritical phases, and scaling laws between anomalous exponents.

Accelerated molecular dynamics and protein conformational change: a theoretical and practical guide using a membrane embedded model neurotransmitter transporter.

PubMed

Gedeon, Patrick C; Thomas, James R; Madura, Jeffry D

2015-01-01

Molecular dynamics simulation provides a powerful and accurate method to model protein conformational change, yet timescale limitations often prevent direct assessment of the kinetic properties of interest. A large number of molecular dynamic steps are necessary for rare events to occur, which allow a system to overcome energy barriers and conformationally transition from one potential energy minimum to another. For many proteins, the energy landscape is further complicated by a multitude of potential energy wells, each separated by high free-energy barriers and each potentially representative of a functionally important protein conformation. To overcome these obstacles, accelerated molecular dynamics utilizes a robust bias potential function to simulate the transition between different potential energy minima. This straightforward approach more efficiently samples conformational space in comparison to classical molecular dynamics simulation, does not require advanced knowledge of the potential energy landscape and converges to the proper canonical distribution. Here, we review the theory behind accelerated molecular dynamics and discuss the approach in the context of modeling protein conformational change. As a practical example, we provide a detailed, step-by-step explanation of how to perform an accelerated molecular dynamics simulation using a model neurotransmitter transporter embedded in a lipid cell membrane. Changes in protein conformation of relevance to the substrate transport cycle are then examined using principle component analysis.

Functional optical coherence tomography for live dynamic analysis of mouse embryonic cardiogenesis

NASA Astrophysics Data System (ADS)

Wang, Shang; Lopez, Andrew L.; Larina, Irina V.

2018-02-01

Blood flow, heart contraction, and tissue stiffness are important regulators of cardiac morphogenesis and function during embryonic development. Defining how these factors are integrated is critically important to advance prevention, diagnostics, and treatment of congenital heart defects. Mammalian embryonic development is taking place deep within the female body, which makes cardiodynamic imaging and analysis during early developmental stages in humans inaccessible. With thousands of mutant lines available and well-established genetic manipulation tools, mouse is a great model to understand how biomechanical factors are integrated with molecular pathways to regulate cardiac function and development. Dynamic imaging and quantitative analysis of the biomechanics of live mouse embryos have become increasingly important, which demands continuous advancements in imaging techniques and live assessment approaches. This has been one of the major drives to keep pushing the frontier of embryonic imaging for better resolution, higher speed, deeper penetration, and more diverse and effective contrasts. Optical coherence tomography (OCT) has played a significant role in addressing such demands, and its features in non-labeling imaging, 3D capability, a large working distance, and various functional derivatives allow OCT to cover a number of specific applications in embryonic imaging. Recently, our group has made several technical improvements in using OCT to probe the biomechanical aspects of live developing mouse embryos at early stages. These include the direct volumetric structural and functional imaging of the cardiodynamics, four-dimensional quantitative Doppler imaging and analysis of the cardiac blood flow, and fourdimensional blood flow separation from the cardiac wall tissue in the beating embryonic heart. Here, we present a short review of these studies together with brief descriptions of the previous work that demonstrate OCT as a valuable and useful imaging tool for the research in developmental cardiology.

Ontogenetic scaling of hydrostatic skeletons: geometric, static stress and dynamic stress scaling of the earthworm lumbricus terrestris

PubMed

Quillin

1998-05-21

Soft-bodied organisms with hydrostatic skeletons range enormously in body size, both during the growth of individuals and in the comparison of species. Therefore, body size is an important consideration in an examination of the mechanical function of hydrostatic skeletons. The scaling of hydrostatic skeletons cannot be inferred from existing studies of the lever-like skeletons of vertebrates and arthropods because the two skeleton types function by different mechanisms. Hydrostats are constructed of an extensible body wall in tension surrounding a fluid or deformable tissue under compression. It is the pressurized internal fluid (rather than the rigid levers of vertebrates and arthropods) that enables the maintenance of posture, antagonism of muscles and transfer of muscle forces to the environment. The objectives of the present study were (1) to define the geometric, static stress and dynamic stress similarity scaling hypotheses for hydrostatic skeletons on the basis of their generalized form and function, and (2) to apply these similarity hypotheses in a study of the ontogenetic scaling of earthworms, Lumbricus terrestris, to determine which parameters of skeletal function are conserved or changed as a function of body mass during growth (from 0.01 to 8 g). Morphometric measurements on anesthetized earthworms revealed that the earthworms grew isometrically; the external proportions and number of segments were constant as a function of body size. Calculations of static stresses (forces per cross-sectional area in the body wall) during rest and dynamic stresses during peristaltic crawling (calculated from measurements of internal pressure and body wall geometry) revealed that the earthworms also maintained static and dynamic stress similarity, despite a slight increase in body wall thickness in segment 50 (but not in segment 15). In summary, the hydrostatic skeletons of earthworms differ fundamentally from the rigid, lever-like skeletons of their terrestrial counterparts in their ability to grow isometrically while maintaining similarity in both static and dynamic stresses.

Warming Alters Expressions of Microbial Functional Genes Important to Ecosystem Functioning

DOE PAGES

Xue, Kai; Xie, Jianping; Zhou, Aifen; ...

2016-05-06

Soil microbial communities play critical roles in ecosystem functioning and are likely altered by climate warming. However, so far, little is known about effects of warming on microbial functional gene expressions. Here, we applied functional gene array (GeoChip 3.0) to analyze cDNA reversely transcribed from total RNA to assess expressed functional genes in active soil microbial communities after nine years of experimental warming in a tallgrass prairie. Our results showed that warming significantly altered the community wide gene expressions. Specifically, expressed genes for degrading more recalcitrant carbon were stimulated by warming, likely linked to the plant community shift toward moremore » C 4 species under warming and to decrease the long-term soil carbon stability. In addition, warming changed expressed genes in labile C degradation and N cycling in different directions (increase and decrease), possibly reflecting the dynamics of labile C and available N pools during sampling. However, the average abundances of expressed genes in phosphorus and sulfur cycling were all increased by warming, implying a stable trend of accelerated P and S processes which might be a mechanism to sustain higher plant growth. Furthermore, the expressed gene composition was closely related to both dynamic (e.g., soil moisture) and stable environmental attributes (e.g., C 4 leaf C or N content), indicating that RNA analyses could also capture certain stable trends in the long-term treatment. Overall, this study revealed the importance of elucidating functional gene expressions of soil microbial community in enhancing our understanding of ecosystem responses to warming.« less

Warming Alters Expressions of Microbial Functional Genes Important to Ecosystem Functioning

PubMed Central

Xue, Kai; Xie, Jianping; Zhou, Aifen; Liu, Feifei; Li, Dejun; Wu, Liyou; Deng, Ye; He, Zhili; Van Nostrand, Joy D.; Luo, Yiqi; Zhou, Jizhong

2016-01-01

Soil microbial communities play critical roles in ecosystem functioning and are likely altered by climate warming. However, so far, little is known about effects of warming on microbial functional gene expressions. Here, we applied functional gene array (GeoChip 3.0) to analyze cDNA reversely transcribed from total RNA to assess expressed functional genes in active soil microbial communities after nine years of experimental warming in a tallgrass prairie. Our results showed that warming significantly altered the community wide gene expressions. Specifically, expressed genes for degrading more recalcitrant carbon were stimulated by warming, likely linked to the plant community shift toward more C4 species under warming and to decrease the long-term soil carbon stability. In addition, warming changed expressed genes in labile C degradation and N cycling in different directions (increase and decrease), possibly reflecting the dynamics of labile C and available N pools during sampling. However, the average abundances of expressed genes in phosphorus and sulfur cycling were all increased by warming, implying a stable trend of accelerated P and S processes which might be a mechanism to sustain higher plant growth. Furthermore, the expressed gene composition was closely related to both dynamic (e.g., soil moisture) and stable environmental attributes (e.g., C4 leaf C or N content), indicating that RNA analyses could also capture certain stable trends in the long-term treatment. Overall, this study revealed the importance of elucidating functional gene expressions of soil microbial community in enhancing our understanding of ecosystem responses to warming. PMID:27199978

Warming Alters Expressions of Microbial Functional Genes Important to Ecosystem Functioning

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

Xue, Kai; Xie, Jianping; Zhou, Aifen

Soil microbial communities play critical roles in ecosystem functioning and are likely altered by climate warming. However, so far, little is known about effects of warming on microbial functional gene expressions. Here, we applied functional gene array (GeoChip 3.0) to analyze cDNA reversely transcribed from total RNA to assess expressed functional genes in active soil microbial communities after nine years of experimental warming in a tallgrass prairie. Our results showed that warming significantly altered the community wide gene expressions. Specifically, expressed genes for degrading more recalcitrant carbon were stimulated by warming, likely linked to the plant community shift toward moremore » C 4 species under warming and to decrease the long-term soil carbon stability. In addition, warming changed expressed genes in labile C degradation and N cycling in different directions (increase and decrease), possibly reflecting the dynamics of labile C and available N pools during sampling. However, the average abundances of expressed genes in phosphorus and sulfur cycling were all increased by warming, implying a stable trend of accelerated P and S processes which might be a mechanism to sustain higher plant growth. Furthermore, the expressed gene composition was closely related to both dynamic (e.g., soil moisture) and stable environmental attributes (e.g., C 4 leaf C or N content), indicating that RNA analyses could also capture certain stable trends in the long-term treatment. Overall, this study revealed the importance of elucidating functional gene expressions of soil microbial community in enhancing our understanding of ecosystem responses to warming.« less

van der Waals interactions are critical in Car-Parrinello molecular dynamics simulations of porphyrin-fullerene dyads.

PubMed

Karilainen, Topi; Cramariuc, Oana; Kuisma, Mikael; Tappura, Kirsi; Hukka, Terttu I

2015-04-05

The interplay between electrostatic and van der Waals (vdW) interactions in porphyrin-C60 dyads is still under debate despite its importance in influencing the structural characteristics of such complexes considered for various applications in molecular photovoltaics. In this article, we sample the conformational space of a porphyrin-C60 dyad using Car-Parrinello molecular dynamics simulations with and without empirical vdW corrections. Long-range vdW interactions, which are poorly described by the commonly used density functional theory functionals, prove to be essential for a proper dynamics of the dyad moieties. Inclusion of vdW corrections brings porphyrin and C60 close together in an orientation that is in agreement with experimental observations. The structural differences arising from the vdW corrections are shown to be significant for several properties and potentially less important for others. Additionally, our Mulliken population analysis reveals that contrary to the common belief, porphyrin is not the primary electron donating moiety for C60 . In the considered dyad, fullerene's affinity for electrons is primarily satisfied by charge transfer from the amide group of the linker. However, we show that in the absence of another suitable bound donor, C60 can withdraw electrons from porphyrin if it is sufficiently close. © 2015 Wiley Periodicals, Inc.

Organelle communication: signaling crossroads between homeostasis and disease.

PubMed

Bravo-Sagua, Roberto; Torrealba, Natalia; Paredes, Felipe; Morales, Pablo E; Pennanen, Christian; López-Crisosto, Camila; Troncoso, Rodrigo; Criollo, Alfredo; Chiong, Mario; Hill, Joseph A; Simmen, Thomas; Quest, Andrew F; Lavandero, Sergio

2014-05-01

Cellular organelles do not function as isolated or static units, but rather form dynamic contacts between one another that can be modulated according to cellular needs. The physical interfaces between organelles are important for Ca2+ and lipid homeostasis, and serve as platforms for the control of many essential functions including metabolism, signaling, organelle integrity and execution of the apoptotic program. Emerging evidence also highlights the importance of organelle communication in disorders such as Alzheimer's disease, pulmonary arterial hypertension, cancer, skeletal and cardiac muscle dysfunction. Here, we provide an overview of the current literature on organelle communication and the link to human pathologies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis of self-assembly of S-layer protein slp-B53 from Lysinibacillus sphaericus.

PubMed

Liu, Jun; Falke, Sven; Drobot, Bjoern; Oberthuer, Dominik; Kikhney, Alexey; Guenther, Tobias; Fahmy, Karim; Svergun, Dmitri; Betzel, Christian; Raff, Johannes

2017-01-01

The formation of stable and functional surface layers (S-layers) via self-assembly of surface-layer proteins on the cell surface is a dynamic and complex process. S-layers facilitate a number of important biological functions, e.g., providing protection and mediating selective exchange of molecules and thereby functioning as molecular sieves. Furthermore, S-layers selectively bind several metal ions including uranium, palladium, gold, and europium, some of them with high affinity. Most current research on surface layers focuses on investigating crystalline arrays of protein subunits in Archaea and bacteria. In this work, several complementary analytical techniques and methods have been applied to examine structure-function relationships and dynamics for assembly of S-layer protein slp-B53 from Lysinibacillus sphaericus: (1) The secondary structure of the S-layer protein was analyzed by circular dichroism spectroscopy; (2) Small-angle X-ray scattering was applied to gain insights into the three-dimensional structure in solution; (3) The interaction with bivalent cations was followed by differential scanning calorimetry; (4) The dynamics and time-dependent assembly of S-layers were followed by applying dynamic light scattering; (5) The two-dimensional structure of the paracrystalline S-layer lattice was examined by atomic force microscopy. The data obtained provide essential structural insights into the mechanism of S-layer self-assembly, particularly with respect to binding of bivalent cations, i.e., Mg 2+ and Ca 2+ . Furthermore, the results obtained highlight potential applications of S-layers in the fields of micromaterials and nanobiotechnology by providing engineered or individual symmetric thin protein layers, e.g., for protective, antimicrobial, or otherwise functionalized surfaces.

Vlasov dynamics of periodically driven systems

NASA Astrophysics Data System (ADS)

Banerjee, Soumyadip; Shah, Kushal

2018-04-01

Analytical solutions of the Vlasov equation for periodically driven systems are of importance in several areas of plasma physics and dynamical systems and are usually approximated using ponderomotive theory. In this paper, we derive the plasma distribution function predicted by ponderomotive theory using Hamiltonian averaging theory and compare it with solutions obtained by the method of characteristics. Our results show that though ponderomotive theory is relatively much easier to use, its predictions are very restrictive and are likely to be very different from the actual distribution function of the system. We also analyse all possible initial conditions which lead to periodic solutions of the Vlasov equation for periodically driven systems and conjecture that the irreducible polynomial corresponding to the initial condition must only have squares of the spatial and momentum coordinate. The resulting distribution function for other initial conditions is aperiodic and can lead to complex relaxation processes within the plasma.

Phase dynamics of coupled oscillators reconstructed from data

NASA Astrophysics Data System (ADS)

Rosenblum, Michael; Kralemann, Bjoern; Pikovsky, Arkady

2013-03-01

We present a technique for invariant reconstruction of the phase dynamics equations for coupled oscillators from data. The invariant description is achieved by means of a transformation of phase estimates (protophases) obtained from general scalar observables to genuine phases. Staring from the bivariate data, we obtain the coupling functions in terms of these phases. We discuss the importance of the protophase-to-phase transformation for characterization of strength and directionality of interaction. To illustrate the technique we analyse the cardio-respiratory interaction on healthy humans. Our invariant approach is confirmed by high similarity of the coupling functions obtained from different observables of the cardiac system. Next, we generalize the technique to cover the case of small networks of coupled periodic units. We use the partial norms of the reconstructed coupling functions to quantify directed coupling between the oscillators. We illustrate the method by different network motifs for three coupled oscillators. We also discuss nonlinear effects in coupling.

Electrophysiological Source Imaging: A Noninvasive Window to Brain Dynamics.

PubMed

He, Bin; Sohrabpour, Abbas; Brown, Emery; Liu, Zhongming

2018-06-04

Brain activity and connectivity are distributed in the three-dimensional space and evolve in time. It is important to image brain dynamics with high spatial and temporal resolution. Electroencephalography (EEG) and magnetoencephalography (MEG) are noninvasive measurements associated with complex neural activations and interactions that encode brain functions. Electrophysiological source imaging estimates the underlying brain electrical sources from EEG and MEG measurements. It offers increasingly improved spatial resolution and intrinsically high temporal resolution for imaging large-scale brain activity and connectivity on a wide range of timescales. Integration of electrophysiological source imaging and functional magnetic resonance imaging could further enhance spatiotemporal resolution and specificity to an extent that is not attainable with either technique alone. We review methodological developments in electrophysiological source imaging over the past three decades and envision its future advancement into a powerful functional neuroimaging technology for basic and clinical neuroscience applications.

Muscle quality, aerobic fitness and fat mass predict lower-extremity physical function in community-dwelling older adults.

PubMed

Misic, Mark M; Rosengren, Karl S; Woods, Jeffrey A; Evans, Ellen M

2007-01-01

Muscle mass, strength and fitness play a role in lower-extremity physical function (LEPF) in older adults; however, the relationships remain inadequately characterized. This study aimed to examine the relationships between leg mineral free lean mass (MFLM(LEG)), leg muscle quality (leg strength normalized for MFLM(LEG)), adiposity, aerobic fitness and LEPF in community-dwelling healthy elderly subjects. Fifty-five older adults (69.3 +/- 5.5 years, 36 females, 19 males) were assessed for leg strength using an isokinetic dynamometer, body composition by dual energy X-ray absorptiometry and aerobic fitness via a treadmill maximal oxygen consumption test. LEPF was assessed using computerized dynamic posturography and stair ascent/descent, a timed up-and-go task and a 7-meter walk with and without an obstacle. Muscle strength, muscle quality and aerobic fitness were similarly correlated with static LEPF tests (r range 0.27-0.40, p < 0.05); however, the strength of the independent predictors was not robust with explained variance ranging from 9 to 16%. Muscle quality was the strongest correlate of all dynamic LEPF tests (r range 0.54-0.65, p < 0.001). Using stepwise linear regression analysis, muscle quality was the strongest independent predictor of dynamic physical function explaining 29-42% of the variance (p < 0.001), whereas aerobic fitness or body fat mass explained 5-6% of the variance (p < 0.05) depending on performance measure. Muscle quality is the most important predictor, and aerobic fitness and fat mass are secondary predictors of LEPF in community-dwelling older adults. These findings support the importance of exercise, especially strength training, for optimal body composition, and maintenance of strength and physical function in older adults.

microRNA regulation of T-cell differentiation and function

PubMed Central

Jeker, Lukas T.; Bluestone, Jeffrey A.

2013-01-01

Summary microRNAs (miRNAs) are emerging as key controllers of T-cell differentiation and function. Their expression is dynamically regulated by extracellular signals such as costimulation and cytokine signals. miRNAs set thresholds for gene expression and optimize protein concentrations of genetic networks. Absence of individual miRNAs can lead to severe immune dysfunction. Here we review emerging principles and provide examples of important functions exerted by miRNAs. Although our understanding of miRNA function in T-cell differentiation is still rudimentary, the available evidence leaves no doubt that these small posttranscriptional regulators are indispensable for proper functioning of the immune system. PMID:23550639

An open-chain imaginary-time path-integral sampling approach to the calculation of approximate symmetrized quantum time correlation functions.

PubMed

Cendagorta, Joseph R; Bačić, Zlatko; Tuckerman, Mark E

2018-03-14

We introduce a scheme for approximating quantum time correlation functions numerically within the Feynman path integral formulation. Starting with the symmetrized version of the correlation function expressed as a discretized path integral, we introduce a change of integration variables often used in the derivation of trajectory-based semiclassical methods. In particular, we transform to sum and difference variables between forward and backward complex-time propagation paths. Once the transformation is performed, the potential energy is expanded in powers of the difference variables, which allows us to perform the integrals over these variables analytically. The manner in which this procedure is carried out results in an open-chain path integral (in the remaining sum variables) with a modified potential that is evaluated using imaginary-time path-integral sampling rather than requiring the generation of a large ensemble of trajectories. Consequently, any number of path integral sampling schemes can be employed to compute the remaining path integral, including Monte Carlo, path-integral molecular dynamics, or enhanced path-integral molecular dynamics. We believe that this approach constitutes a different perspective in semiclassical-type approximations to quantum time correlation functions. Importantly, we argue that our approximation can be systematically improved within a cumulant expansion formalism. We test this approximation on a set of one-dimensional problems that are commonly used to benchmark approximate quantum dynamical schemes. We show that the method is at least as accurate as the popular ring-polymer molecular dynamics technique and linearized semiclassical initial value representation for correlation functions of linear operators in most of these examples and improves the accuracy of correlation functions of nonlinear operators.

An open-chain imaginary-time path-integral sampling approach to the calculation of approximate symmetrized quantum time correlation functions

NASA Astrophysics Data System (ADS)

Cendagorta, Joseph R.; Bačić, Zlatko; Tuckerman, Mark E.

2018-03-01

We introduce a scheme for approximating quantum time correlation functions numerically within the Feynman path integral formulation. Starting with the symmetrized version of the correlation function expressed as a discretized path integral, we introduce a change of integration variables often used in the derivation of trajectory-based semiclassical methods. In particular, we transform to sum and difference variables between forward and backward complex-time propagation paths. Once the transformation is performed, the potential energy is expanded in powers of the difference variables, which allows us to perform the integrals over these variables analytically. The manner in which this procedure is carried out results in an open-chain path integral (in the remaining sum variables) with a modified potential that is evaluated using imaginary-time path-integral sampling rather than requiring the generation of a large ensemble of trajectories. Consequently, any number of path integral sampling schemes can be employed to compute the remaining path integral, including Monte Carlo, path-integral molecular dynamics, or enhanced path-integral molecular dynamics. We believe that this approach constitutes a different perspective in semiclassical-type approximations to quantum time correlation functions. Importantly, we argue that our approximation can be systematically improved within a cumulant expansion formalism. We test this approximation on a set of one-dimensional problems that are commonly used to benchmark approximate quantum dynamical schemes. We show that the method is at least as accurate as the popular ring-polymer molecular dynamics technique and linearized semiclassical initial value representation for correlation functions of linear operators in most of these examples and improves the accuracy of correlation functions of nonlinear operators.

β-Cell Ca(2+) dynamics and function are compromised in aging.

PubMed

Barker, Christopher J; Li, Luosheng; Köhler, Martin; Berggren, Per-Olof

2015-01-01

Defects in pancreatic β-cell function and survival are key components in type 2 diabetes (T2D). An age-dependent deterioration in β-cell function has also been observed, but little is known about the molecular mechanisms behind this phenomenon. Our previous studies indicate that the regulation of cytoplasmic free Ca(2+) concentration ([Ca(2+)]i) may be critical and that this is dependent on the proper function of the mitochondria. The [Ca(2+)]i dynamics of the pancreatic β-cell are driven by an interplay between glucose-induced influx of extracellular Ca(2+) via voltage-dependent Ca(2+) channels and the inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)-mediated liberation of Ca(2+) from intracellular stores. Our previous work has indicated a direct relationship between disruption of Ins(1,4,5)P3-mediated Ca(2+) regulation and loss of β-cell function, including disturbed [Ca(2+)]i dynamics and compromised insulin secretion. To investigate these processes in aging we used three mouse models, a premature aging mitochondrial mutator mouse, a mature aging phenotype (C57BL/6) and an aging-resistant phenotype (129). Our data suggest that age-dependent impairment in mitochondrial function leads to modest changes in [Ca(2+)]i dynamics in mouse β-cells, particularly in the pattern of [Ca(2+)]i oscillations. These changes are driven by modifications in both PLC/Ins(1,4,5)P3-mediated Ca(2+) mobilization from intracellular stores and decreased β-cell Ca(2+) influx over the plasma membrane. Our findings underscore an important concept, namely that even relatively small, time-dependent changes in β-cell signal-transduction result in compromised insulin release and in a diabetic phenotype. Copyright © 2014 Elsevier Ltd. All rights reserved.

The origin and dynamic evolution of chemical information transfer

PubMed Central

Steiger, Sandra; Schmitt, Thomas; Schaefer, H. Martin

2011-01-01

Although chemical communication is the most widespread form of communication, its evolution and diversity are not well understood. By integrating studies of a wide range of terrestrial plants and animals, we show that many chemicals are emitted, which can unintentionally provide information (cues) and, therefore, act as direct precursors for the evolution of intentional communication (signals). Depending on the content, design and the original function of the cue, there are predictable ways that selection can enhance the communicative function of chemicals. We review recent progress on how efficacy-based selection by receivers leads to distinct evolutionary trajectories of chemical communication. Because the original function of a cue may channel but also constrain the evolution of functional communication, we show that a broad perspective on multiple selective pressures acting upon chemicals provides important insights into the origin and dynamic evolution of chemical information transfer. Finally, we argue that integrating chemical ecology into communication theory may significantly enhance our understanding of the evolution, the design and the content of signals in general. PMID:21177681

BAR domain proteins regulate Rho GTPase signaling.

PubMed

Aspenström, Pontus

2014-01-01

BAR proteins comprise a heterogeneous group of multi-domain proteins with diverse biological functions. The common denominator is the Bin-Amphiphysin-Rvs (BAR) domain that not only confers targeting to lipid bilayers, but also provides scaffolding to mold lipid membranes into concave or convex surfaces. This function of BAR proteins is an important determinant in the dynamic reconstruction of membrane vesicles, as well as of the plasma membrane. Several BAR proteins function as linkers between cytoskeletal regulation and membrane dynamics. These links are provided by direct interactions between BAR proteins and actin-nucleation-promoting factors of the Wiskott-Aldrich syndrome protein family and the Diaphanous-related formins. The Rho GTPases are key factors for orchestration of this intricate interplay. This review describes how BAR proteins regulate the activity of Rho GTPases, as well as how Rho GTPases regulate the function of BAR proteins. This mutual collaboration is a central factor in the regulation of vital cellular processes, such as cell migration, cytokinesis, intracellular transport, endocytosis, and exocytosis.

Di-hadron production at Jefferson Laboratory

NASA Astrophysics Data System (ADS)

Anefalos Pereira, Sergio; CLAS Collaboration

2015-04-01

Semi-inclusive deep inelastic scattering (SIDIS) has been used extensively in recent years as an important testing ground for QCD. Studies so far have concentrated on better determination of parton distribution functions, distinguishing between the quark and antiquark contributions, and understanding the fragmentation of quarks into hadrons. Pair of hadrons (di-hadron) SIDIS provides information on the nucleon structure and hadronization dynamics that complements single-hadron SIDIS. The study of di-hadrons allow us to study higher twist distribution functions and Dihadron Fragmentation Functions (DiFF). Together with the twist-2 PDFs (f 1, g 1, h 1), the Higher Twist (HT) e and hL functions are very interesting because they offer insights into the physics of the largely unexplored quark-gluon correlations which provide direct and unique insights into the dynamics inside hadrons. The CLAS spectrometer, installed in Hall-B at Jefferson Lab, has collected data using the CEBAF 6 GeV longitudinally polarized electron beam on longitudinally polarized solid NH3 targets. Preliminary results on beam-, target- and double-spin asymmetries will be presented.

PLAU inferred from a correlation network is critical for suppressor function of regulatory T cells

PubMed Central

He, Feng; Chen, Hairong; Probst-Kepper, Michael; Geffers, Robert; Eifes, Serge; del Sol, Antonio; Schughart, Klaus; Zeng, An-Ping; Balling, Rudi

2012-01-01

Human FOXP3+CD25+CD4+ regulatory T cells (Tregs) are essential to the maintenance of immune homeostasis. Several genes are known to be important for murine Tregs, but for human Tregs the genes and underlying molecular networks controlling the suppressor function still largely remain unclear. Here, we describe a strategy to identify the key genes directly from an undirected correlation network which we reconstruct from a very high time-resolution (HTR) transcriptome during the activation of human Tregs/CD4+ T-effector cells. We show that a predicted top-ranked new key gene PLAU (the plasminogen activator urokinase) is important for the suppressor function of both human and murine Tregs. Further analysis unveils that PLAU is particularly important for memory Tregs and that PLAU mediates Treg suppressor function via STAT5 and ERK signaling pathways. Our study demonstrates the potential for identifying novel key genes for complex dynamic biological processes using a network strategy based on HTR data, and reveals a critical role for PLAU in Treg suppressor function. PMID:23169000

Implicit Self-Importance in an Interpersonal Pronoun Categorization Task.

PubMed

Fetterman, Adam K; Robinson, Michael D; Gilbertson, Elizabeth P

2014-06-01

Object relations theories emphasize the manner in which the salience/importance of implicit representations of self and other guide interpersonal functioning. Two studies and a pilot test (total N = 304) sought to model such representations. In dyadic contexts, the self is a "you" and the other is a "me", as verified in a pilot test. Study 1 then used a simple categorization task and found evidence for implicit self-importance: The pronoun "you" was categorized more quickly and accurately when presented in a larger font size, whereas the pronoun "me" was categorized more quickly and accurately when presented in a smaller font size. Study 2 showed that this pattern possesses value in understanding individual differences in interpersonal functioning. As predicted, arrogant people scored higher in implicit self-importance in the paradigm. Findings are discussed from the perspective of dyadic interpersonal dynamics.

Molecular Dynamics Simulations Provide Atomistic Insight into Hydrogen Exchange Mass Spectrometry Experiments.

PubMed

Petruk, Ariel A; Defelipe, Lucas A; Rodríguez Limardo, Ramiro G; Bucci, Hernán; Marti, Marcelo A; Turjanski, Adrian G

2013-01-08

It is now clear that proteins are flexible entities that in solution switch between conformations to achieve their function. Hydrogen/Deuterium Exchange Mass Spectrometry (HX/MS) is an invaluable tool to understand dynamic changes in proteins modulated by cofactor binding, post-transductional modifications, or protein-protein interactions. ERK2MAPK, a protein involved in highly conserved signal transduction pathways of paramount importance for normal cellular function, has been extensively studied by HX/MS. Experiments of the ERK2MAPK in the inactive and active states (in the presence or absence of bound ATP) have provided valuable information on the plasticity of the MAPK domain. However, interpretation of the HX/MS data is difficult, and changes are mostly explained in relation to available X-ray structures, precluding a complete atomic picture of protein dynamics. In the present work, we have used all atom Molecular Dynamics simulations (MD) to provide a theoretical framework for the interpretation of HX/MS data. Our results show that detailed analysis of protein-solvent interaction along the MD simulations allows (i) prediction of the number of protons exchanged for each peptide in the HX/MS experiments, (ii) rationalization of the experimentally observed changes in exchange rates in different protein conditions at the residue level, and (iii) that at least for ERK2MAPK, most of the functionally observed differences in protein dynamics are related to what can be considered the native state conformational ensemble. In summary, the combination of HX/MS experiments with all atom MD simulations emerges as a powerful approach to study protein native state dynamics with atomic resolution.

Storm-time radiation belt electron dynamics: Repeatability in the outer radiation belt

NASA Astrophysics Data System (ADS)

Murphy, K. R.; Mann, I. R.; Rae, J.; Watt, C.; Boyd, A. J.; Turner, D. L.; Claudepierre, S. G.; Baker, D. N.; Spence, H. E.; Reeves, G. D.; Blake, J. B.; Fennell, J. F.

2017-12-01

During intervals of enhanced solar wind driving the outer radiation belt becomes extremely dynamic leading to geomagnetic storms. During these storms the flux of energetic electrons can vary by over 4 orders of magnitude. Despite recent advances in understanding the nature of competing storm-time electron loss and acceleration processes the dynamic behavior of the outer radiation belt remains poorly understood; the outer radiation belt can exhibit either no change, an enhancement, or depletion in radiation belt electrons. Using a new analysis of the total radiation belt electron content, calculated from the Van Allen probes phase space density (PSD), we statistically analyze the time-dependent and global response of the outer radiation belt during storms. We demonstrate that by removing adiabatic effects there is a clear and repeatable sequence of events in storm-time radiation belt electron dynamics. Namely, the relativistic (μ=1000 MeV/G) and ultra-relativistic (μ=4000 MeV/G) electron populations can be separated into two phases; an initial phase dominated by loss followed by a second phase dominated by acceleration. At lower energies, the radiation belt seed population of electrons (μ=150 MeV/G) shows no evidence of loss but rather a net enhancement during storms. Further, we investigate the dependence of electron dynamics as a function of the second adiabatic invariant, K. These results demonstrate a global coherency in the dynamics of the source, relativistic and ultra-relativistic electron populations as function of the second adiabatic invariant K. This analysis demonstrates two key aspects of storm-time radiation belt electron dynamics. First, the radiation belt responds repeatably to solar wind driving during geomagnetic storms. Second, the response of the radiation belt is energy dependent, relativistic electrons behaving differently than lower energy seed electrons. These results have important implications in radiation belt research. In particular, the repeatability in electron dynamics coupled with observations of processes leading to electron loss (EMIC waves) and acceleration (VLF or ULF waves) can be used to diagnose the relative importance of physical processes in radiation belt dynamics during storms.

Cumulative soil water evaporation as a function of depth and time

USDA-ARS?s Scientific Manuscript database

Soil water evaporation is an important component of the surface water balance and the surface energy balance. Accurate and dynamic measurements of soil water evaporation enhance the understanding of water and energy partitioning at the land-atmosphere interface. The objective of this study is to mea...

Why Research-Informed Teaching in Engineering Education? A Review of the Evidence

ERIC Educational Resources Information Center

Bubou, Gordon Monday; Offor, Ibebietei Temple; Bappa, Abubakar Saddiq

2017-01-01

Challenges of today's engineering education (EE) are emergent, necessitating calls for its reformation to empower future engineers function optimally as innovative leaders, in both local and international contexts. These challenges: keeping pace with technological dynamism; high attrition; and most importantly, quality teaching/learning require…

Web-based Distributed Medical Information System for Chronic Viral Hepatitis

NASA Astrophysics Data System (ADS)

Yang, Ying; Qin, Tuan-fa; Jiang, Jian-ning; Lu, Hui; Ma, Zong-e.; Meng, Hong-chang

2008-11-01

To make a long-term dynamic monitoring to the chronically ill, especially patients of HBV A, we build a distributed Medical Information System for Chronic Viral Hepatitis (MISCHV). The Web-based system architecture and its function are described, and the extensive application and important role are also presented.

Mediated Development: A Vygotskian Approach to Transforming Second Language Learner Abilities

ERIC Educational Resources Information Center

Poehner, Matthew E.; Infante, Paolo

2017-01-01

The authors point to systemic-theoretical instruction (STI), which underscores the importance of abstract conceptual knowledge in schooling, and dynamic assessment (DA), in which mediators and learners function cooperatively, as examples of the theory-practice relation envisioned by Vygotsky (1987). This article proposes an interactional framework…

Results of an Analysis of Field Studies of the Intrinsic Dynamic Characteristics Important for the Safety of Nuclear Power Plant Equipment

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

Kaznovsky, A. P., E-mail: kaznovskyap@atech.ru; Kasiyanov, K. G.; Ryasnyj, S. I.

2015-01-15

A classification of the equipment important for the safety of nuclear power plants is proposed in terms of its dynamic behavior under seismic loading. An extended bank of data from dynamic tests over the entire range of thermal and mechanical equipment in generating units with VVER-1000 and RBMK-1000 reactors is analyzed. Results are presented from a study of the statistical behavior of the distribution of vibrational frequencies and damping decrements with the “small perturbation” factor that affects the measured damping decrements taken into account. A need to adjust the regulatory specifications for choosing the values of the damping decrements withmore » specified inertial loads on equipment owing to seismic effects during design calculations is identified. Minimum values of the decrements are determined and proposed for all types of equipment as functions of the directions and natural vibration frequencies of the dynamic interactions to be adopted as conservative standard values in the absence of actual experimental data in the course of design studies of seismic resistance.« less

MD Simulations of tRNA and Aminoacyl-tRNA Synthetases: Dynamics, Folding, Binding, and Allostery

PubMed Central

Li, Rongzhong; Macnamara, Lindsay M.; Leuchter, Jessica D.; Alexander, Rebecca W.; Cho, Samuel S.

2015-01-01

While tRNA and aminoacyl-tRNA synthetases are classes of biomolecules that have been extensively studied for decades, the finer details of how they carry out their fundamental biological functions in protein synthesis remain a challenge. Recent molecular dynamics (MD) simulations are verifying experimental observations and providing new insight that cannot be addressed from experiments alone. Throughout the review, we briefly discuss important historical events to provide a context for how far the field has progressed over the past few decades. We then review the background of tRNA molecules, aminoacyl-tRNA synthetases, and current state of the art MD simulation techniques for those who may be unfamiliar with any of those fields. Recent MD simulations of tRNA dynamics and folding and of aminoacyl-tRNA synthetase dynamics and mechanistic characterizations are discussed. We highlight the recent successes and discuss how important questions can be addressed using current MD simulations techniques. We also outline several natural next steps for computational studies of AARS:tRNA complexes. PMID:26184179

The fundamental role of quantized vibrations in coherent light harvesting by cryptophyte algae

NASA Astrophysics Data System (ADS)

Kolli, Avinash; O'Reilly, Edward J.; Scholes, Gregory D.; Olaya-Castro, Alexandra

2012-11-01

The influence of fast vibrations on energy transfer and conversion in natural molecular aggregates is an issue of central interest. This article shows the important role of high-energy quantized vibrations and their non-equilibrium dynamics for energy transfer in photosynthetic systems with highly localized excitonic states. We consider the cryptophyte antennae protein phycoerythrin 545 and show that coupling to quantized vibrations, which are quasi-resonant with excitonic transitions is fundamental for biological function as it generates non-cascaded transport with rapid and wider spatial distribution of excitation energy. Our work also indicates that the non-equilibrium dynamics of such vibrations can manifest itself in ultrafast beating of both excitonic populations and coherences at room temperature, with time scales in agreement with those reported in experiments. Moreover, we show that mechanisms supporting coherent excitonic dynamics assist coupling to selected modes that channel energy to preferential sites in the complex. We therefore argue that, in the presence of strong coupling between electronic excitations and quantized vibrations, a concrete and important advantage of quantum coherent dynamics is precisely to tune resonances that promote fast and effective energy distribution.

Regulating energy transfer of excited carriers and the case for excitation-induced hydrogen dissociation on hydrogenated graphene

PubMed Central

Bang, Junhyeok; Meng, Sheng; Sun, Yi-Yang; West, Damien; Wang, Zhiguo; Gao, Fei; Zhang, S. B.

2013-01-01

Understanding and controlling of excited carrier dynamics is of fundamental and practical importance, particularly in photochemistry and solar energy applications. However, theory of energy relaxation of excited carriers is still in its early stage. Here, using ab initio molecular dynamics (MD) coupled with time-dependent density functional theory, we show a coverage-dependent energy transfer of photoexcited carriers in hydrogenated graphene, giving rise to distinctively different ion dynamics. Graphene with sparsely populated H is difficult to dissociate due to inefficient transfer of the excitation energy into kinetic energy of the H. In contrast, H can easily desorb from fully hydrogenated graphane. The key is to bring down the H antibonding state to the conduction band minimum as the band gap increases. These results can be contrasted to those of standard ground-state MD that predict H in the sparse case should be much less stable than that in fully hydrogenated graphane. Our findings thus signify the importance of carrying out explicit electronic dynamics in excited-state simulations. PMID:23277576

Functional relationship-based alarm processing system

DOEpatents

Corsberg, D.R.

1988-04-22

A functional relationship-based alarm processing system and method analyzes each alarm as it is activated and determines its relative importance with other currently activated alarms and signals in accordance with the functional relationships that the newly activated alarm has with other currently activated alarms. Once the initial level of importance of the alarm has been determined, that alarm is again evaluated if another related alarm is activated or deactivated. Thus, each alarm's importance is continuously updated as the state of the process changes during a scenario. Four hierarchical relationships are defined by this alarm filtering methodology: (1) level precursor (usually occurs when there are two alarm settings on the same parameter); (2) direct precursor (based on causal factors between two alarms); (3) required action (system response or action expected within a specified time following activation of an alarm or combination of alarms and process signals); and (4) blocking condition (alarms that are normally expected and are not considered important). The alarm processing system and method is sensitive to the dynamic nature of the process being monitored and is capable of changing the relative importance of each alarm as necessary. 12 figs.

Functional relationship-based alarm processing system

DOEpatents

Corsberg, Daniel R.

1989-01-01

A functional relationship-based alarm processing system and method analyzes each alarm as it is activated and determines its relative importance with other currently activated alarms and signals in accordance with the functional relationships that the newly activated alarm has with other currently activated alarms. Once the initial level of importance of the alarm has been determined, that alarm is again evaluated if another related alarm is activated or deactivated. Thus, each alarm's importance is continuously updated as the state of the process changes during a scenario. Four hierarchical relationships are defined by this alarm filtering methodology: (1) level precursor (usually occurs when there are two alarm settings on the same parameter); (2) direct precursor (based on causal factors between two alarms); (3) required action (system response or action expected within a specified time following activation of an alarm or combination of alarms and process signals); and (4) blocking condition (alarms that are normally expected and are not considered important). The alarm processing system and method is sensitive to the dynamic nature of the process being monitored and is capable of changing the relative importance of each alarm as necessary.

The Fluid-Mosaic Model of Membrane Structure: still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years.

PubMed

Nicolson, Garth L

2014-06-01

In 1972 the Fluid-Mosaic Membrane Model of membrane structure was proposed based on thermodynamic principals of organization of membrane lipids and proteins and available evidence of asymmetry and lateral mobility within the membrane matrix [S. J. Singer and G. L. Nicolson, Science 175 (1972) 720-731]. After over 40years, this basic model of the cell membrane remains relevant for describing the basic nano-structures of a variety of intracellular and cellular membranes of plant and animal cells and lower forms of life. In the intervening years, however, new information has documented the importance and roles of specialized membrane domains, such as lipid rafts and protein/glycoprotein complexes, in describing the macrostructure, dynamics and functions of cellular membranes as well as the roles of membrane-associated cytoskeletal fences and extracellular matrix structures in limiting the lateral diffusion and range of motion of membrane components. These newer data build on the foundation of the original model and add new layers of complexity and hierarchy, but the concepts described in the original model are still applicable today. In updated versions of the model more emphasis has been placed on the mosaic nature of the macrostructure of cellular membranes where many protein and lipid components are limited in their rotational and lateral motilities in the membrane plane, especially in their natural states where lipid-lipid, protein-protein and lipid-protein interactions as well as cell-matrix, cell-cell and intracellular membrane-associated protein and cytoskeletal interactions are important in restraining the lateral motility and range of motion of particular membrane components. The formation of specialized membrane domains and the presence of tightly packed integral membrane protein complexes due to membrane-associated fences, fenceposts and other structures are considered very important in describing membrane dynamics and architecture. These structures along with membrane-associated cytoskeletal and extracellular structures maintain the long-range, non-random mosaic macro-organization of membranes, while smaller membrane nano- and submicro-sized domains, such as lipid rafts and protein complexes, are important in maintaining specialized membrane structures that are in cooperative dynamic flux in a crowded membrane plane. This Article is Part of a Special Issue Entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy. © 2013.

On Stabilizing the Variance of Dynamic Functional Brain Connectivity Time Series

PubMed Central

Fransson, Peter

2016-01-01

Abstract Assessment of dynamic functional brain connectivity based on functional magnetic resonance imaging (fMRI) data is an increasingly popular strategy to investigate temporal dynamics of the brain's large-scale network architecture. Current practice when deriving connectivity estimates over time is to use the Fisher transformation, which aims to stabilize the variance of correlation values that fluctuate around varying true correlation values. It is, however, unclear how well the stabilization of signal variance performed by the Fisher transformation works for each connectivity time series, when the true correlation is assumed to be fluctuating. This is of importance because many subsequent analyses either assume or perform better when the time series have stable variance or adheres to an approximate Gaussian distribution. In this article, using simulations and analysis of resting-state fMRI data, we analyze the effect of applying different variance stabilization strategies on connectivity time series. We focus our investigation on the Fisher transformation, the Box–Cox (BC) transformation and an approach that combines both transformations. Our results show that, if the intention of stabilizing the variance is to use metrics on the time series, where stable variance or a Gaussian distribution is desired (e.g., clustering), the Fisher transformation is not optimal and may even skew connectivity time series away from being Gaussian. Furthermore, we show that the suboptimal performance of the Fisher transformation can be substantially improved by including an additional BC transformation after the dynamic functional connectivity time series has been Fisher transformed. PMID:27784176

On Stabilizing the Variance of Dynamic Functional Brain Connectivity Time Series.

PubMed

Thompson, William Hedley; Fransson, Peter

2016-12-01

Assessment of dynamic functional brain connectivity based on functional magnetic resonance imaging (fMRI) data is an increasingly popular strategy to investigate temporal dynamics of the brain's large-scale network architecture. Current practice when deriving connectivity estimates over time is to use the Fisher transformation, which aims to stabilize the variance of correlation values that fluctuate around varying true correlation values. It is, however, unclear how well the stabilization of signal variance performed by the Fisher transformation works for each connectivity time series, when the true correlation is assumed to be fluctuating. This is of importance because many subsequent analyses either assume or perform better when the time series have stable variance or adheres to an approximate Gaussian distribution. In this article, using simulations and analysis of resting-state fMRI data, we analyze the effect of applying different variance stabilization strategies on connectivity time series. We focus our investigation on the Fisher transformation, the Box-Cox (BC) transformation and an approach that combines both transformations. Our results show that, if the intention of stabilizing the variance is to use metrics on the time series, where stable variance or a Gaussian distribution is desired (e.g., clustering), the Fisher transformation is not optimal and may even skew connectivity time series away from being Gaussian. Furthermore, we show that the suboptimal performance of the Fisher transformation can be substantially improved by including an additional BC transformation after the dynamic functional connectivity time series has been Fisher transformed.

Mechanical compaction directly modulates the dynamics of bile canaliculi formation.

PubMed

Wang, Yan; Toh, Yi-Chin; Li, Qiushi; Nugraha, Bramasta; Zheng, Baixue; Lu, Thong Beng; Gao, Yi; Ng, Mary Mah Lee; Yu, Hanry

2013-02-01

Homeostatic pressure-driven compaction is a ubiquitous mechanical force in multicellular organisms and is proposed to be important in the maintenance of multicellular tissue integrity and function. Previous cell-free biochemical models have demonstrated that there are cross-talks between compaction forces and tissue structural functions, such as cell-cell adhesion. However, its involvement in physiological tissue function has yet to be directly demonstrated. Here, we use the bile canaliculus (BC) as a physiological example of a multicellular functional structure in the liver, and employ a novel 3D microfluidic hepatocyte culture system to provide an unprecedented opportunity to experimentally modulate the compaction states of primary hepatocyte aggregates in a 3D physiological-mimicking environment. Mechanical compaction alters the physical attributes of the hepatocyte aggregates, including cell shape, cell packing density and cell-cell contact area, but does not impair the hepatocytes' remodeling and functional capabilities. Characterization of structural and functional polarity shows that BC formation in compact hepatocyte aggregates is accelerated to as early as 12 hours post-seeding; whereas non-compact control requires 48 hours for functional BC formation. Further dynamic immunofluorescence imaging and gene expression profiling reveal that compaction accelerated BC formation is accompanied by changes in actin cytoskeleton remodeling dynamics and transcriptional levels of hepatic nuclear factor 4α and Annexin A2. Our report not only provides a novel strategy of modeling BC formation for in vitro hepatology research, but also shows a first instance that homeostatic pressure-driven compaction force is directly coupled to the higher-order multicellular functions.

Lipid-Mediated Regulation of Embedded Receptor Kinases via Parallel Allosteric Relays.

PubMed

Ghosh, Madhubrata; Wang, Loo Chien; Ramesh, Ranita; Morgan, Leslie K; Kenney, Linda J; Anand, Ganesh S

2017-02-28

Membrane-anchored receptors are essential cellular signaling elements for stimulus sensing, propagation, and transmission inside cells. However, the contributions of lipid interactions to the function and dynamics of embedded receptor kinases have not been described in detail. In this study, we used amide hydrogen/deuterium exchange mass spectrometry, a sensitive biophysical approach, to probe the dynamics of a membrane-embedded receptor kinase, EnvZ, together with functional assays to describe the role of lipids in receptor kinase function. Our results reveal that lipids play an important role in regulating receptor function through interactions with transmembrane segments, as well as through peripheral interactions with nonembedded domains. Specifically, the lipid membrane allosterically modulates the activity of the embedded kinase by altering the dynamics of a glycine-rich motif that is critical for phosphotransfer from ATP. This allostery in EnvZ is independent of membrane composition and involves direct interactions with transmembrane and periplasmic segments, as well as peripheral interactions with nonembedded domains of the protein. In the absence of the membrane-spanning regions, lipid allostery is propagated entirely through peripheral interactions. Whereas lipid allostery impacts the phosphotransferase function of the kinase, extracellular stimulus recognition is mediated via a four-helix bundle subdomain located in the cytoplasm, which functions as the osmosensing core through osmolality-dependent helical stabilization. Our findings emphasize the functional modularity in a membrane-embedded kinase, separated into membrane association, phosphotransferase function, and stimulus recognition. These components are integrated through long-range communication relays, with lipids playing an essential role in regulation. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Transient Cognitive Dynamics, Metastability, and Decision Making

PubMed Central

Rabinovich, Mikhail I.; Huerta, Ramón; Varona, Pablo; Afraimovich, Valentin S.

2008-01-01

The idea that cognitive activity can be understood using nonlinear dynamics has been intensively discussed at length for the last 15 years. One of the popular points of view is that metastable states play a key role in the execution of cognitive functions. Experimental and modeling studies suggest that most of these functions are the result of transient activity of large-scale brain networks in the presence of noise. Such transients may consist of a sequential switching between different metastable cognitive states. The main problem faced when using dynamical theory to describe transient cognitive processes is the fundamental contradiction between reproducibility and flexibility of transient behavior. In this paper, we propose a theoretical description of transient cognitive dynamics based on the interaction of functionally dependent metastable cognitive states. The mathematical image of such transient activity is a stable heteroclinic channel, i.e., a set of trajectories in the vicinity of a heteroclinic skeleton that consists of saddles and unstable separatrices that connect their surroundings. We suggest a basic mathematical model, a strongly dissipative dynamical system, and formulate the conditions for the robustness and reproducibility of cognitive transients that satisfy the competing requirements for stability and flexibility. Based on this approach, we describe here an effective solution for the problem of sequential decision making, represented as a fixed time game: a player takes sequential actions in a changing noisy environment so as to maximize a cumulative reward. As we predict and verify in computer simulations, noise plays an important role in optimizing the gain. PMID:18452000

Structured crowding and its effects on enzyme catalysis.

PubMed

Ma, Buyong; Nussinov, Ruth

2013-01-01

Macromolecular crowding decreases the diffusion rate, shifts the equilibrium of protein-protein and protein-substrate interactions, and changes protein conformational dynamics. Collectively, these effects contribute to enzyme catalysis. Here we describe how crowding may bias the conformational change and dynamics of enzyme populations and in this way affect catalysis. Crowding effects have been studied using artificial crowding agents and in vivo-like environments. These studies revealed a correlation between protein dynamics and function in the crowded environment. We suggest that crowded environments be classified into uniform crowding and structured crowding. Uniform crowding represents random crowding conditions created by synthetic particles with a narrow size distribution. Structured crowding refers to the highly coordinated cellular environment, where proteins and other macromolecules are clustered and organized. In structured crowded environments the perturbation of protein thermal stability may be lower; however, it may still be able to modulate functions effectively and dynamically. Dynamic, allosteric enzymes could be more sensitive to cellular perturbations if their free energy landscape is flatter around the native state; on the other hand, if their free energy landscape is rougher, with high kinetic barriers separating deep minima, they could be more robust. Above all, cells are structured; and this holds both for the cytosol and for the membrane environment. The crowded environment is organized, which limits the search, and the crowders are not necessarily inert. More likely, they too transmit allosteric effects, and as such play important functional roles. Overall, structured cellular crowding may lead to higher enzyme efficiency and specificity.

Characterizing dynamic amplitude of low-frequency fluctuation and its relationship with dynamic functional connectivity: An application to schizophrenia.

PubMed

Fu, Zening; Tu, Yiheng; Di, Xin; Du, Yuhui; Pearlson, G D; Turner, J A; Biswal, Bharat B; Zhang, Zhiguo; Calhoun, V D

2017-09-20

The human brain is a highly dynamic system with non-stationary neural activity and rapidly-changing neural interaction. Resting-state dynamic functional connectivity (dFC) has been widely studied during recent years, and the emerging aberrant dFC patterns have been identified as important features of many mental disorders such as schizophrenia (SZ). However, only focusing on the time-varying patterns in FC is not enough, since the local neural activity itself (in contrast to the inter-connectivity) is also found to be highly fluctuating from research using high-temporal-resolution imaging techniques. Exploring the time-varying patterns in brain activity and their relationships with time-varying brain connectivity is important for advancing our understanding of the co-evolutionary property of brain network and the underlying mechanism of brain dynamics. In this study, we introduced a framework for characterizing time-varying brain activity and exploring its associations with time-varying brain connectivity, and applied this framework to a resting-state fMRI dataset including 151 SZ patients and 163 age- and gender matched healthy controls (HCs). In this framework, 48 brain regions were first identified as intrinsic connectivity networks (ICNs) using group independent component analysis (GICA). A sliding window approach was then adopted for the estimation of dynamic amplitude of low-frequency fluctuation (dALFF) and dFC, which were used to measure time-varying brain activity and time-varying brain connectivity respectively. The dALFF was further clustered into six reoccurring states by the k-means clustering method and the group difference in occurrences of dALFF states was explored. Lastly, correlation coefficients between dALFF and dFC were calculated and the group difference in these dALFF-dFC correlations was explored. Our results suggested that 1) ALFF of brain regions was highly fluctuating during the resting-state and such dynamic patterns are altered in SZ, 2) dALFF and dFC were correlated in time and their correlations are altered in SZ. The overall results support and expand prior work on abnormalities of brain activity, static FC (sFC) and dFC in SZ, and provide new evidence on aberrant time-varying brain activity and its associations with brain connectivity in SZ, which might underscore the disrupted brain cognitive functions in this mental disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

Network-Level Structure-Function Relationships in Human Neocortex

PubMed Central

Mišić, Bratislav; Betzel, Richard F.; de Reus, Marcel A.; van den Heuvel, Martijn P.; Berman, Marc G.; McIntosh, Anthony R.; Sporns, Olaf

2016-01-01

The dynamics of spontaneous fluctuations in neural activity are shaped by underlying patterns of anatomical connectivity. While numerous studies have demonstrated edge-wise correspondence between structural and functional connections, much less is known about how large-scale coherent functional network patterns emerge from the topology of structural networks. In the present study, we deploy a multivariate statistical technique, partial least squares, to investigate the association between spatially extended structural networks and functional networks. We find multiple statistically robust patterns, reflecting reliable combinations of structural and functional subnetworks that are optimally associated with one another. Importantly, these patterns generally do not show a one-to-one correspondence between structural and functional edges, but are instead distributed and heterogeneous, with many functional relationships arising from nonoverlapping sets of anatomical connections. We also find that structural connections between high-degree hubs are disproportionately represented, suggesting that these connections are particularly important in establishing coherent functional networks. Altogether, these results demonstrate that the network organization of the cerebral cortex supports the emergence of diverse functional network configurations that often diverge from the underlying anatomical substrate. PMID:27102654

Emergent properties of interacting populations of spiking neurons.

PubMed

Cardanobile, Stefano; Rotter, Stefan

2011-01-01

Dynamic neuronal networks are a key paradigm of increasing importance in brain research, concerned with the functional analysis of biological neuronal networks and, at the same time, with the synthesis of artificial brain-like systems. In this context, neuronal network models serve as mathematical tools to understand the function of brains, but they might as well develop into future tools for enhancing certain functions of our nervous system. Here, we present and discuss our recent achievements in developing multiplicative point processes into a viable mathematical framework for spiking network modeling. The perspective is that the dynamic behavior of these neuronal networks is faithfully reflected by a set of non-linear rate equations, describing all interactions on the population level. These equations are similar in structure to Lotka-Volterra equations, well known by their use in modeling predator-prey relations in population biology, but abundant applications to economic theory have also been described. We present a number of biologically relevant examples for spiking network function, which can be studied with the help of the aforementioned correspondence between spike trains and specific systems of non-linear coupled ordinary differential equations. We claim that, enabled by the use of multiplicative point processes, we can make essential contributions to a more thorough understanding of the dynamical properties of interacting neuronal populations.

Emergent Properties of Interacting Populations of Spiking Neurons

PubMed Central

Cardanobile, Stefano; Rotter, Stefan

2011-01-01

Dynamic neuronal networks are a key paradigm of increasing importance in brain research, concerned with the functional analysis of biological neuronal networks and, at the same time, with the synthesis of artificial brain-like systems. In this context, neuronal network models serve as mathematical tools to understand the function of brains, but they might as well develop into future tools for enhancing certain functions of our nervous system. Here, we present and discuss our recent achievements in developing multiplicative point processes into a viable mathematical framework for spiking network modeling. The perspective is that the dynamic behavior of these neuronal networks is faithfully reflected by a set of non-linear rate equations, describing all interactions on the population level. These equations are similar in structure to Lotka-Volterra equations, well known by their use in modeling predator-prey relations in population biology, but abundant applications to economic theory have also been described. We present a number of biologically relevant examples for spiking network function, which can be studied with the help of the aforementioned correspondence between spike trains and specific systems of non-linear coupled ordinary differential equations. We claim that, enabled by the use of multiplicative point processes, we can make essential contributions to a more thorough understanding of the dynamical properties of interacting neuronal populations. PMID:22207844

Integrating 'omic' data and biogeochemical modeling: the key to understanding the microbial regulation of matter cycling in soil

NASA Astrophysics Data System (ADS)

Pagel, Holger; Kandeler, Ellen; Seifert, Jana; Camarinha-Silva, Amélia; Kügler, Philipp; Rennert, Thilo; Poll, Christian; Streck, Thilo

2016-04-01

Matter cycling in soils and associated soil functions are intrinsically controlled by microbial dynamics. It is therefore crucial to consider functional traits of microorganisms in biogeochemical models. Tremendous advances in 'omic' methods provide a plethora of data on physiology, metabolic capabilities and ecological life strategies of microorganisms in soil. Combined with isotopic techniques, biochemical pathways and transformations can be identified and quantified. Such data have been, however, rarely used to improve the mechanistic representation of microbial dynamics in soil organic matter models. It is the goal of the Young Investigator Group SoilReg to address this challenge. Our general approach is to tightly integrate experiments and biochemical modeling. NextGen sequencing will be applied to identify key functional groups. Active microbial groups will be quantified by measurements of functional genes and by stable isotope probing methods of DNA and proteins. Based on this information a biogeochemical model that couples a mechanistic representation of microbial dynamics with physicochemical processes will be set up and calibrated. Sensitivity and stability analyses of the model as well as scenario simulations will reveal the importance of intrinsic and extrinsic controls of organic matter turnover. We will demonstrate our concept and present first results of two case studies on pesticide degradation and methane oxidation.

Amplitude, Latency, and Peak Velocity in Accommodation and Disaccommodation Dynamics

PubMed Central

Papadatou, Eleni; Ferrer-Blasco, Teresa; Montés-Micó, Robert

2017-01-01

The aim of this work was to ascertain whether there are differences in amplitude, latency, and peak velocity of accommodation and disaccommodation responses when different analysis strategies are used to compute them, such as fitting different functions to the responses or for smoothing them prior to computing the parameters. Accommodation and disaccommodation responses from four subjects to pulse changes in demand were recorded by means of aberrometry. Three different strategies were followed to analyze such responses: fitting an exponential function to the experimental data; fitting a Boltzmann sigmoid function to the data; and smoothing the data. Amplitude, latency, and peak velocity of the responses were extracted. Significant differences were found between the peak velocity in accommodation computed by fitting an exponential function and smoothing the experimental data (mean difference 2.36 D/s). Regarding disaccommodation, significant differences were found between latency and peak velocity, calculated with the two same strategies (mean difference of 0.15 s and −3.56 D/s, resp.). The strategy used to analyze accommodation and disaccommodation responses seems to affect the parameters that describe accommodation and disaccommodation dynamics. These results highlight the importance of choosing the most adequate analysis strategy in each individual to obtain the parameters that characterize accommodation and disaccommodation dynamics. PMID:29226128

Evidence for Conformationa1 Heterogeneity of Fission Protein Fis1 from Saccharomyces cerevisiae†

PubMed Central

Picton, Lora K.; Casares, Salvador; Monahan, Ann C.; Majumdar, Ananya; Hill, R. Blake

2009-01-01

Fission 1 (Fis1) is an evolutionarily conserved, type II integral membrane protein implicated in maintaining the proper morphology of mitochondria and peroxisomes. A concave surface on the cytosolic domain of Fis1 from Saccharomyces cerevisiae is implicated in binding other fission proteins, yet structural studies reveal that this surface is sterically occluded by its N-terminal arm. Here we address the question of whether the N-terminal arm of yeast Fis1 exists in a dynamic equilibrium that would allow access to this functionally important surface. NMR measurements sensitive to dynamics occurring on a wide range of time scales (picoseconds to minutes) were used to assess whether the Fis1 arm is dynamic. Hydrogen–deuterium exchange experiments revealed that the Fis1 arm, α-helix 6, and proximal loops were not protected from solvent exchange, consistent with motions on the second to minute time scale. An engineered cysteine, I85C, located on the concave surface that lies underneath the Fis1 arm, was readily modified by a fluorescent probe, revealing more solvent accessibility of this position than would be predicted from the structure. Chemical denaturation, NMR chemical shift perturbation, and residual dipolar coupling experiments support the idea that the dynamic equilibrium can be shifted on the basis of changing pH and temperature, with the changes primarily localizing to the Fis1 arm and proximal regions. The data as a whole are consistent with the Fis1 arm adopting a primarily “closed” conformational state able to undergo dynamic excursions that reveal the concave surface and therefore may be important for binding other fission factors and for Fis1 function. PMID:19522466

Effect of molecular shape on rotation under severe confinement

DOE PAGES

Dhiman, Indu; Bhowmik, Debsindhu; Shrestha, Utsab R.; ...

2018-01-31

Orientational structure and dynamics of molecules is known to be affected by confinement in space comparable in size to the molecule itself. ZSM-5 with porous channels of ≈0.55 nm is such a porous medium, which offers a strict spatial confinement on low molecular weight hydrocarbons. An important factor that determines these properties is the shape of the confined molecules. In this work, we employed molecular dynamics simulation to study the orientational structure and dynamics of four molecules that differ in shape but have similar kinetic diameters and moments of inertia, confined in ZSM-5. The effect of molecular shape on themore » orientational structure and dynamics of propane, acetonitrile, acetaldehyde and acetone in ZSM-5 is studied by means of probing the differences in the orientational distribution of molecules in the ZSM-5 channels, and extracting time scales of the decay of correlation functions related to rotational motion. Orientational correlation functions of all the four molecules exhibit two regimes of rotational motion. While the short time regime represents free rotation of the molecules before they collide with the pore walls, the long time orientational jumps driven by inter-channel migrations give rise to a very slow varying second regime. Of the molecules studied, orientational structure and dynamics of propane is found to be least affected by confinement under ZSM-5, whereas charge and shape asymmetry of other molecules makes their interchannel migration-driven rotation slow. The time scales involved in the rotational motion for the molecules studied are compared with similar studies reported in literature. Lastly, this study reveals the important role that molecular shape plays in the behavior of confined molecules.« less

Effect of molecular shape on rotation under severe confinement

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

Dhiman, Indu; Bhowmik, Debsindhu; Shrestha, Utsab R.

Orientational structure and dynamics of molecules is known to be affected by confinement in space comparable in size to the molecule itself. ZSM-5 with porous channels of ≈0.55 nm is such a porous medium, which offers a strict spatial confinement on low molecular weight hydrocarbons. An important factor that determines these properties is the shape of the confined molecules. In this work, we employed molecular dynamics simulation to study the orientational structure and dynamics of four molecules that differ in shape but have similar kinetic diameters and moments of inertia, confined in ZSM-5. The effect of molecular shape on themore » orientational structure and dynamics of propane, acetonitrile, acetaldehyde and acetone in ZSM-5 is studied by means of probing the differences in the orientational distribution of molecules in the ZSM-5 channels, and extracting time scales of the decay of correlation functions related to rotational motion. Orientational correlation functions of all the four molecules exhibit two regimes of rotational motion. While the short time regime represents free rotation of the molecules before they collide with the pore walls, the long time orientational jumps driven by inter-channel migrations give rise to a very slow varying second regime. Of the molecules studied, orientational structure and dynamics of propane is found to be least affected by confinement under ZSM-5, whereas charge and shape asymmetry of other molecules makes their interchannel migration-driven rotation slow. The time scales involved in the rotational motion for the molecules studied are compared with similar studies reported in literature. Lastly, this study reveals the important role that molecular shape plays in the behavior of confined molecules.« less

Theory of dynamic barriers, activated hopping, and the glass transition in polymer melts

NASA Astrophysics Data System (ADS)

Schweizer, Kenneth S.; Saltzman, Erica J.

2004-07-01

A statistical mechanical theory of collective dynamic barriers, slow segmental relaxation, and the glass transition of polymer melts is developed by combining, and in some aspects extending, methods of mode coupling, density functional, and activated hopping transport theories. A coarse-grained description of polymer chains is adopted and the melt is treated as a liquid of segments. The theory is built on the idea that collective density fluctuations on length scales considerably longer than the local cage scale are of primary importance in the deeply supercooled regime. The barrier hopping or segmental relaxation time is predicted to be a function primarily of a single parameter that is chemical structure, temperature, and pressure dependent. This parameter depends on the material-specific dimensionless amplitude of thermal density fluctuations (compressibility) and a reduced segmental density determined by the packing length and backbone characteristic ratio. Analytic results are derived for a crossover temperature Tc, collective barrier, and glass transition temperature Tg. The relation of these quantities to structural and thermodynamic properties of the polymer melt is established. A universal power-law scaling behavior of the relaxation time below Tc is predicted based on identification of a reduced temperature variable that quantifies the breadth of the supercooled regime. Connections between the ratio Tc/Tg, two measures of dynamic fragility, and the magnitude of the local relaxation time at Tg logically follow. Excellent agreement with experiment is found for these generic aspects, and the crucial importance of the experimentally observed near universality of the dynamic crossover time is established. Extensions of the theory to treat the full chain dynamics, heterogeneity, barrier fluctuations, and nonpolymeric thermal glass forming liquids are briefly discussed.

Tom7 modulates the dynamics of the mitochondrial outer membrane translocase and plays a pathway-related role in protein import.

PubMed Central

Hönlinger, A; Bömer, U; Alconada, A; Eckerskorn, C; Lottspeich, F; Dietmeier, K; Pfanner, N

1996-01-01

The preprotein translocase of the outer mitochondrial membrane is a multi-subunit complex with receptors and a general import pore. We report the molecular identification of Tom7, a small subunit of the translocase that behaves as an integral membrane protein. The deletion of TOM7 inhibited the mitochondrial import of the outer membrane protein porin, whereas the import of preproteins destined for the mitochondrial interior was impaired only slightly. However, protein import into the mitochondrial interior was strongly inhibited when it occurred in two steps: preprotein accumulation at the outer membrane in the absence of a membrane potential and subsequent further import after the re-establishment of a membrane potential. The delay of protein import into tom7delta mitochondria seemed to occur after the binding of preproteins to the outer membrane receptor sites. A lack of Tom7 stabilized the interaction between the receptors Tom20 and Tom22 and the import pore component Tom40. This indicated that Tom7 exerts a destabilizing effect on part of the outer membrane translocase, whereas Tom6 stabilizes the interaction between the receptors and the import pore. Synthetic growth defects of the double mutants tom7delta tom20delta and tom7delta tom6delta provided genetic evidence for the functional relationship of Tom7 with Tom20 and Tom6. These results suggest that (i) Tom7 plays a role in sorting and accumulation of the preproteins at the outer membrane, and (ii) Tom7 and Tom6 perform complementary functions in modulating the dynamics of the outer membrane translocase. Images PMID:8641278

Is a healthy ecosystem one that is rich in parasites?

USGS Publications Warehouse

Hudson, Peter J.; Dobson, Andrew P.; Lafferty, Kevin D.

2006-01-01

Historically, the role of parasites in ecosystem functioning has been considered trivial because a cursory examination reveals that their relative biomass is low compared with that of other trophic groups. However there is increasing evidence that parasite-mediated effects could be significant: they shape host population dynamics, alter interspecific competition, influence energy flow and appear to be important drivers of biodiversity. Indeed they influence a range of ecosystem functions and have a major effect on the structure of some food webs. Here, we consider the bottom-up and top-down processes of how parasitism influences ecosystem functioning and show that there is evidence that parasites are important for biodiversity and production; thus, we consider a healthy system to be one that is rich in parasite species.

Risperidone Effects on Brain Dynamic Connectivity-A Prospective Resting-State fMRI Study in Schizophrenia.

PubMed

Lottman, Kristin K; Kraguljac, Nina V; White, David M; Morgan, Charity J; Calhoun, Vince D; Butt, Allison; Lahti, Adrienne C

2017-01-01

Resting-state functional connectivity studies in schizophrenia evaluating average connectivity over the entire experiment have reported aberrant network integration, but findings are variable. Examining time-varying (dynamic) functional connectivity may help explain some inconsistencies. We assessed dynamic network connectivity using resting-state functional MRI in patients with schizophrenia, while unmedicated ( n  = 34), after 1 week ( n  = 29) and 6 weeks of treatment with risperidone ( n  = 24), as well as matched controls at baseline ( n  = 35) and after 6 weeks ( n  = 19). After identifying 41 independent components (ICs) comprising resting-state networks, sliding window analysis was performed on IC timecourses using an optimal window size validated with linear support vector machines. Windowed correlation matrices were then clustered into three discrete connectivity states (a relatively sparsely connected state, a relatively abundantly connected state, and an intermediately connected state). In unmedicated patients, static connectivity was increased between five pairs of ICs and decreased between two pairs of ICs when compared to controls, dynamic connectivity showed increased connectivity between the thalamus and somatomotor network in one of the three states. State statistics indicated that, in comparison to controls, unmedicated patients had shorter mean dwell times and fraction of time spent in the sparsely connected state, and longer dwell times and fraction of time spent in the intermediately connected state. Risperidone appeared to normalize mean dwell times after 6 weeks, but not fraction of time. Results suggest that static connectivity abnormalities in schizophrenia may partly be related to altered brain network temporal dynamics rather than consistent dysconnectivity within and between functional networks and demonstrate the importance of implementing complementary data analysis techniques.

A Functional Cartography of Cognitive Systems

PubMed Central

Mattar, Marcelo G.; Cole, Michael W.; Thompson-Schill, Sharon L.; Bassett, Danielle S.

2015-01-01

One of the most remarkable features of the human brain is its ability to adapt rapidly and efficiently to external task demands. Novel and non-routine tasks, for example, are implemented faster than structural connections can be formed. The neural underpinnings of these dynamics are far from understood. Here we develop and apply novel methods in network science to quantify how patterns of functional connectivity between brain regions reconfigure as human subjects perform 64 different tasks. By applying dynamic community detection algorithms, we identify groups of brain regions that form putative functional communities, and we uncover changes in these groups across the 64-task battery. We summarize these reconfiguration patterns by quantifying the probability that two brain regions engage in the same network community (or putative functional module) across tasks. These tools enable us to demonstrate that classically defined cognitive systems—including visual, sensorimotor, auditory, default mode, fronto-parietal, cingulo-opercular and salience systems—engage dynamically in cohesive network communities across tasks. We define the network role that a cognitive system plays in these dynamics along the following two dimensions: (i) stability vs. flexibility and (ii) connected vs. isolated. The role of each system is therefore summarized by how stably that system is recruited over the 64 tasks, and how consistently that system interacts with other systems. Using this cartography, classically defined cognitive systems can be categorized as ephemeral integrators, stable loners, and anything in between. Our results provide a new conceptual framework for understanding the dynamic integration and recruitment of cognitive systems in enabling behavioral adaptability across both task and rest conditions. This work has important implications for understanding cognitive network reconfiguration during different task sets and its relationship to cognitive effort, individual variation in cognitive performance, and fatigue. PMID:26629847

Dynamic Properties of the International Space Station throughout the Assembly Process

DTIC Science & Technology

1998-06-29

with the launch of the Russian-built FGB, or Functional Cargo Block (most fitting translation) atop a Russian Proton rocket in June of 1998. Phase Two...experiments were conducted in areas of plant growth, life sciences, and microgravity science. But more importantly, Mir-Shuttle operations presented...Configuration Rationale/Comments 30Jun 1998 1 A/R Russian Proton • Functional Cargo Block (FGB) • FGB is a self-supporting active vehicle. • It provides

Functional magnetic resonance imaging phase synchronization as a measure of dynamic functional connectivity.

PubMed

Glerean, Enrico; Salmi, Juha; Lahnakoski, Juha M; Jääskeläinen, Iiro P; Sams, Mikko

2012-01-01

Functional brain activity and connectivity have been studied by calculating intersubject and seed-based correlations of hemodynamic data acquired with functional magnetic resonance imaging (fMRI). To inspect temporal dynamics, these correlation measures have been calculated over sliding time windows with necessary restrictions on the length of the temporal window that compromises the temporal resolution. Here, we show that it is possible to increase temporal resolution by using instantaneous phase synchronization (PS) as a measure of dynamic (time-varying) functional connectivity. We applied PS on an fMRI dataset obtained while 12 healthy volunteers watched a feature film. Narrow frequency band (0.04-0.07 Hz) was used in the PS analysis to avoid artifactual results. We defined three metrics for computing time-varying functional connectivity and time-varying intersubject reliability based on estimation of instantaneous PS across the subjects: (1) seed-based PS, (2) intersubject PS, and (3) intersubject seed-based PS. Our findings show that these PS-based metrics yield results consistent with both seed-based correlation and intersubject correlation methods when inspected over the whole time series, but provide an important advantage of maximal single-TR temporal resolution. These metrics can be applied both in studies with complex naturalistic stimuli (e.g., watching a movie or listening to music in the MRI scanner) and more controlled (e.g., event-related or blocked design) paradigms. A MATLAB toolbox FUNPSY ( http://becs.aalto.fi/bml/software.html ) is openly available for using these metrics in fMRI data analysis.

Density-dependence as a size-independent regulatory mechanism.

PubMed

de Vladar, Harold P

2006-01-21

The growth function of populations is central in biomathematics. The main dogma is the existence of density-dependence mechanisms, which can be modelled with distinct functional forms that depend on the size of the population. One important class of regulatory functions is the theta-logistic, which generalizes the logistic equation. Using this model as a motivation, this paper introduces a simple dynamical reformulation that generalizes many growth functions. The reformulation consists of two equations, one for population size, and one for the growth rate. Furthermore, the model shows that although population is density-dependent, the dynamics of the growth rate does not depend either on population size, nor on the carrying capacity. Actually, the growth equation is uncoupled from the population size equation, and the model has only two parameters, a Malthusian parameter rho and a competition coefficient theta. Distinct sign combinations of these parameters reproduce not only the family of theta-logistics, but also the van Bertalanffy, Gompertz and Potential Growth equations, among other possibilities. It is also shown that, except for two critical points, there is a general size-scaling relation that includes those appearing in the most important allometric theories, including the recently proposed Metabolic Theory of Ecology. With this model, several issues of general interest are discussed such as the growth of animal population, extinctions, cell growth and allometry, and the effect of environment over a population.

The Role of Noise in Brain Function

NASA Astrophysics Data System (ADS)

Roy, S.; Llinás, R.

2012-12-01

Noise plays a fundamental role in all living organisms from the earliest prokaryotes to advanced mammalian forms, such as ourselves. In the context of living organisms, the term 'noise' usually refers to the variance amongst measurements obtained from repeated identical experimental conditions, or from output signals from these systems. It is noteworthy that both these conditions are universally characterized by the presence of background fluctuations. In non-biological systems, such as electronics or in communications sciences, where the aim is to send error-free messages, noise was generally regarded as a problem. The discovery of Stochastic Resonances (SR) in non-linear dynamics brought a shift of perception where noise, rather than representing a problem, became fundamental to system function, especially so in biology. The question now is: to what extent is biological function dependent on random noise. Indeed, it seems feasible that noise also plays an important role in neuronal communication and oscillatory synchronization. Given this approach, it follows that determining Fisher information content could be relevant in neuronal communication. It also seems possible that the principle of least time, and that of the sum over histories, could be important basic principles in understanding the coherence dynamics responsible for action and perception. Ultimately, external noise cancellation combined with intrinsic noise signal embedding and, the use of the principle of least time may be considered an essential step in the organization of central nervous system (CNS) function.

Phase transitions in the first-passage time of scale-invariant correlated processes

PubMed Central

Carretero-Campos, Concepción; Bernaola-Galván, Pedro; Ch. Ivanov, Plamen

2012-01-01

A key quantity describing the dynamics of complex systems is the first-passage time (FPT). The statistical properties of FPT depend on the specifics of the underlying system dynamics. We present a unified approach to account for the diversity of statistical behaviors of FPT observed in real-world systems. We find three distinct regimes, separated by two transition points, with fundamentally different behavior for FPT as a function of increasing strength of the correlations in the system dynamics: stretched exponential, power-law, and saturation regimes. In the saturation regime, the average length of FPT diverges proportionally to the system size, with important implications for understanding electronic delocalization in one-dimensional correlated-disordered systems. PMID:22400544

Biophysical EPR Studies Applied to Membrane Proteins

PubMed Central

Sahu, Indra D; Lorigan, Gary A

2015-01-01

Membrane proteins are very important in controlling bioenergetics, functional activity, and initializing signal pathways in a wide variety of complicated biological systems. They also represent approximately 50% of the potential drug targets. EPR spectroscopy is a very popular and powerful biophysical tool that is used to study the structural and dynamic properties of membrane proteins. In this article, a basic overview of the most commonly used EPR techniques and examples of recent applications to answer pertinent structural and dynamic related questions on membrane protein systems will be presented. PMID:26855825

Lattice dynamics and elasticity for ε-plutonium [First-principles lattice dynamics for ε-plutonium

DOE PAGES

Söderlind, Per

2017-04-25

Here, lattice dynamics and elasticity for the high-temperature ε phase (body-centered cubic; bcc) of plutonium is predicted utilizing first-principles electronic structure coupled with a self-consistent phonon method that takes phonon-phonon interaction and strong anharmonicity into account. These predictions establish the first sensible lattice-dynamics and elasticity data on ε-Pu. The atomic forces required for the phonon scheme are highly accurate and derived from the total energies obtained from relativistic and parameter-free density-functional theory. The results appear reasonable but no data exist to compare with except those from dynamical mean-field theory that suggest ε-plutonium is mechanically unstable. Fundamental knowledge and understanding ofmore » the high-temperature bcc phase, that is generally present in all actinide metals before melting, is critically important for a proper interpretation of the phase diagram as well as practical modeling of high-temperature properties.« less

Interaction quench dynamics in the Kondo model in the presence of a local magnetic field.

PubMed

Heyl, M; Kehrein, S

2010-09-01

In this work we investigate the quench dynamics in the Kondo model on the Toulouse line in the presence of a local magnetic field. It is shown that this setup can be realized by either applying the local magnetic field directly or by preparing the system in a macroscopically spin-polarized initial state. In the latter case, the magnetic field results from a subtlety in applying the bosonization technique where terms that are usually referred to as finite-size corrections become important in the present non-equilibrium setting. The transient dynamics are studied by analyzing exact analytical results for the local spin dynamics. The timescale for the relaxation of the local dynamical quantities turns out to be exclusively determined by the Kondo scale. In the transient regime, one observes damped oscillations in the local correlation functions with a frequency set by the magnetic field.

Dynamical regimes due to technological change in a microeconomical model of production.

PubMed

Hamacher, K

2012-09-01

We develop a microeconomical model to investigate the impact of technological change onto production decisions of suppliers-modeling an effective feedback mechanism of the market. An important property-the time horizon of production planning-is related to the Kolmogorov entropy of the one-dimensional maps describing price dynamics. We simulate this price dynamics in an ensemble representing the whole macroeconomy. We show how this model can be used to support ongoing research in economic growth and incorporate the obtained microeconomic findings into the discussion about appropriate macroeconomic quantities such as the production function-thus effectively underpinning macroeconomics with microeconomical dynamics. From there we can show that the model exhibits different dynamical regimes (suggesting "phase transitions") with respect to an order parameter. The non-linear feedback under technological change was found to be the crucial mechanism. The implications of the obtained regimes are finally discussed.

Respiratory mechanics and fluid dynamics after lung resection surgery.

PubMed

Miserocchi, Giuseppe; Beretta, Egidio; Rivolta, Ilaria

2010-08-01

Thoracic surgery that requires resection of a portion of lung or of a whole lung profoundly alters the mechanical and fluid dynamic setting of the lung-chest wall coupling, as well as the water balance in the pleural space and in the remaining lung. The most frequent postoperative complications are of a respiratory nature, and their incidence increases the more the preoperative respiratory condition seems compromised. There is an obvious need to identify risk factors concerning mainly the respiratory function, without neglecting the importance of other comorbidities, such as coronary disease. At present, however, a satisfactory predictor of postoperative cardiopulmonary complications is lacking; postoperative morbidity and mortality have remained unchanged in the last 10 years. The aim of this review is to provide a pathophysiologic interpretation of the main respiratory complications of a respiratory nature by relying on new concepts relating to lung fluid dynamics and mechanics. New parameters are proposed to improve evaluation of respiratory function from pre- to the early postoperative period when most of the complications occur. Published by Elsevier Inc.

CLASP2 interacts with p120-catenin and governs microtubule dynamics at adherens junctions

PubMed Central

Shahbazi, Marta N.; Megias, Diego; Epifano, Carolina; Akhmanova, Anna; Gundersen, Gregg G.; Fuchs, Elaine

2013-01-01

Classical cadherins and their connections with microtubules (MTs) are emerging as important determinants of cell adhesion. However, the functional relevance of such interactions and the molecular players that contribute to tissue architecture are still emerging. In this paper, we report that the MT plus end–binding protein CLASP2 localizes to adherens junctions (AJs) via direct interaction with p120-catenin (p120) in primary basal mouse keratinocytes. Reductions in the levels of p120 or CLASP2 decreased the localization of the other protein to cell–cell contacts and altered AJ dynamics and stability. These features were accompanied by decreased MT density and altered MT dynamics at intercellular junction sites. Interestingly, CLASP2 was enriched at the cortex of basal progenitor keratinocytes, in close localization to p120. Our findings suggest the existence of a new mechanism of MT targeting to AJs with potential functional implications in the maintenance of proper cell–cell adhesion in epidermal stem cells. PMID:24368809

On the nature of a glassy state of matter in a hydrated protein: Relation to protein function.

PubMed

Teeter, M M; Yamano, A; Stec, B; Mohanty, U

2001-09-25

Diverse biochemical and biophysical experiments indicate that all proteins, regardless of size or origin, undergo a dynamic transition near 200 K. The cause of this shift in dynamic behavior, termed a "glass transition," and its relation to protein function are important open questions. One explanation postulated for the transition is solidification of correlated motions in proteins below the transition. We verified this conjecture by showing that crambin's radius of gyration (Rg) remains constant below approximately 180 K. We show that both atom position and dynamics of protein and solvent are physically coupled, leading to a novel cooperative state. This glassy state is identified by negative slopes of the Debye-Waller (B) factor vs. temperature. It is composed of multisubstate side chains and solvent. Based on generalization of Adam-Gibbs' notion of a cooperatively rearranging region and decrease of the total entropy with temperature, we calculate the slope of the Debye-Waller factor. The results are in accord with experiment.

Photon echo spectroscopy reveals structure-dynamics relationships in carotenoids

NASA Astrophysics Data System (ADS)

Christensson, N.; Polivka, T.; Yartsev, A.; Pullerits, T.

2009-06-01

Based on simultaneous analysis of the frequency-resolved transient grating, peak shift, and echo width signals, we present a model for the third-order optical response of carotenoids including population dynamics and system-bath interactions. Our frequency-resolved photon echo experiments show that the model needs to incorporate the excited-state absorption from both the S2 and the S1 states. We apply our model to analyze the experimental results on astaxanthin and lycopene, aiming to elucidate the relation between structure and system-bath interactions. Our analysis allows us to relate structural motifs to changes in the energy-gap correlation functions. We find that the terminal rings of astaxanthin lead to increased coupling between slow molecular motions and the electronic transition. We also find evidence for stronger coupling to higher frequency overdamped modes in astaxanthin, pointing to the importance of the functional groups in providing coupling to fluctuations influencing the dynamics in the passage through the conical intersection governing the S2-S1 relaxation.

Exploring spatial evolution of economic clusters: A case study of Beijing

NASA Astrophysics Data System (ADS)

Yang, Zhenshan; Sliuzas, Richard; Cai, Jianming; Ottens, Henk F. L.

2012-10-01

An identification of economic clusters and analysing their changing spatial patterns is important for understanding urban economic space dynamics. Previous studies, however, suffer from limitations as a consequence of using fixed geographically areas and not combining functional and spatial dynamics. The paper presents an approach, based on local spatial statistics and the case of Beijing to understand the spatial clustering of industries that are functionally interconnected by common or complementary patterns of demand or supply relations. Using register data of business establishments, it identifies economic clusters and analyses their pattern based on postcodes at different time slices during the period 1983-2002. The study shows how the advanced services occupy the urban centre and key sub centres. The Information and Communication Technology (ICT) cluster is mainly concentrated in the north part of the city and circles the urban centre, and the main manufacturing clusters are evolved in the key sub centers. This type of outcomes improves understanding of urban-economic dynamics, which can support spatial and economic planning.

Atomistic Molecular Dynamics Simulations of Mitochondrial DNA Polymerase γ: Novel Mechanisms of Function and Pathogenesis.

PubMed

Euro, Liliya; Haapanen, Outi; Róg, Tomasz; Vattulainen, Ilpo; Suomalainen, Anu; Sharma, Vivek

2017-03-07

DNA polymerase γ (Pol γ) is a key component of the mitochondrial DNA replisome and an important cause of neurological diseases. Despite the availability of its crystal structures, the molecular mechanism of DNA replication, the switch between polymerase and exonuclease activities, the site of replisomal interactions, and functional effects of patient mutations that do not affect direct catalysis have remained elusive. Here we report the first atomistic classical molecular dynamics simulations of the human Pol γ replicative complex. Our simulation data show that DNA binding triggers remarkable changes in the enzyme structure, including (1) completion of the DNA-binding channel via a dynamic subdomain, which in the apo form blocks the catalytic site, (2) stabilization of the structure through the distal accessory β-subunit, and (3) formation of a putative transient replisome-binding platform in the "intrinsic processivity" subdomain of the enzyme. Our data indicate that noncatalytic mutations may disrupt replisomal interactions, thereby causing Pol γ-associated neurodegenerative disorders.

First principles molecular dynamics of metal/water interfaces under bias potential

NASA Astrophysics Data System (ADS)

Pedroza, Luana; Brandimarte, Pedro; Rocha, Alexandre; Fernandez-Serra, Marivi

2014-03-01

Understanding the interaction of the water-metal system at an atomic level is extremely important in electrocatalysts for fuel cells, photocatalysis among other systems. The question of the interface energetics involves a detailed study of the nature of the interactions between water-water and water-substrate. A first principles description of all components of the system is the most appropriate methodology in order to advance understanding of electrochemically processes. In this work we describe, using first principles molecular dynamics simulations, the dynamics of a combined surface(Au and Pd)/water system both in the presence and absence of an external bias potential applied to the electrodes, as one would come across in electrochemistry. This is accomplished using a combination of density functional theory (DFT) and non-equilibrium Green's functions methods (NEGF), thus accounting for the fact that one is dealing with an out-of-equilibrium open system, with and without van der Waals interactions. DOE Early Career Award No. DE-SC0003871.

Genetic algorithms for the application of Activated Sludge Model No. 1.

PubMed

Kim, S; Lee, H; Kim, J; Kim, C; Ko, J; Woo, H; Kim, S

2002-01-01

The genetic algorithm (GA) has been integrated into the IWA ASM No. 1 to calibrate important stoichiometric and kinetic parameters. The evolutionary feature of GA was used to configure the multiple local optima as well as the global optimum. The objective function of optimization was designed to minimize the difference between estimated and measured effluent concentrations at the activated sludge system. Both steady state and dynamic data of the simulation benchmark were used for calibration using denitrification layout. Depending upon the confidence intervals and objective functions, the proposed method provided distributions of parameter space. Field data have been collected and applied to validate calibration capacity of GA. Dynamic calibration was suggested to capture periodic variations of inflow concentrations. Also, in order to verify this proposed method in real wastewater treatment plant, measured data sets for substrate concentrations were obtained from Haeundae wastewater treatment plant and used to estimate parameters in the dynamic system. The simulation results with calibrated parameters matched well with the observed concentrations of effluent COD.

Rock-salt structure lithium deuteride formation in liquid lithium with high-concentrations of deuterium: a first-principles molecular dynamics study

DOE PAGES

Chen, Mohan; Abrams, T.; Jaworski, M. A.; ...

2015-12-17

Because of lithium's possible use as a first wall material in a fusion reactor, a fundamental understanding of the interactions between liquid lithium (Li) and deuterium (D) is important. Here, we predict structural and dynamical properties of liquid Li samples with high concentrations of D, as derived from first-principles molecular dynamics simulations. Liquid Li samples with four concentrations of inserted D atoms (LiDmore » $$_{\\beta}$$ , $$\\beta =0.25$$ , 0.50, 0.75, and 1.00) are studied at temperatures ranging from 470 to 1143 K. Densities, diffusivities, pair distribution functions, bond angle distribution functions, geometries, and charge transfer between Li and D atoms are calculated and analyzed. The analysis suggests liquid–solid phase transitions can occur at some concentrations and temperatures, forming rock-salt LiD within liquid Li. Finally, we observed the formation of some D 2 molecules at high D concentrations.« less

Two-color single-photon emission from InAs quantum dots: toward logic information management using quantum light.

PubMed

Rivas, David; Muñoz-Matutano, Guillermo; Canet-Ferrer, Josep; García-Calzada, Raúl; Trevisi, Giovanna; Seravalli, Luca; Frigeri, Paola; Martínez-Pastor, Juan P

2014-02-12

In this work, we propose the use of the Hanbury-Brown and Twiss interferometric technique and a switchable two-color excitation method for evaluating the exciton and noncorrelated electron-hole dynamics associated with single photon emission from indium arsenide (InAs) self-assembled quantum dots (QDs). Using a microstate master equation model we demonstrate that our single QDs are described by nonlinear exciton dynamics. The simultaneous detection of two-color, single photon emission from InAs QDs using these nonlinear dynamics was used to design a NOT AND logic transference function. This computational functionality combines the advantages of working with light/photons as input/output device parameters (all-optical system) and that of a nanodevice (QD size of ∼ 20 nm) while also providing high optical sensitivity (ultralow optical power operational requirements). These system features represent an important and interesting step toward the development of new prototypes for the incoming quantum information technologies.

Aspirin locally disrupts the liquid-ordered phase

NASA Astrophysics Data System (ADS)

Alsop, Richard J.; Himbert, Sebastian; Dhaliwal, Alexander; Schmalzl, Karin; Rheinstädter, Maikel C.

2018-02-01

Local structure and dynamics of lipid membranes play an important role in membrane function. The diffusion of small molecules, the curvature of lipids around a protein and the existence of cholesterol-rich lipid domains (rafts) are examples for the membrane to serve as a functional interface. The collective fluctuations of lipid tails, in particular, are relevant for diffusion of membrane constituents and small molecules in and across membranes, and for structure and formation of membrane domains. We studied the effect of aspirin (acetylsalicylic acid, ASA) on local structure and dynamics of membranes composed of dimyristoylphosphocholine (DMPC) and cholesterol. Aspirin is a common analgesic, but is also used in the treatment of cholesterol. Using coherent inelastic neutron scattering experiments and molecular dynamics (MD) simulations, we present evidence that ASA binds to liquid-ordered, raft-like domains and disturbs domain organization and dampens collective fluctuations. By hydrogen-bonding to lipid molecules, ASA forms `superfluid' complexes with lipid molecules that can organize laterally in superlattices and suppress cholesterol's ordering effect.

Protein functional landscapes, dynamics, allostery: a tortuous path towards a universal theoretical framework.

PubMed

Zhuravlev, Pavel I; Papoian, Garegin A

2010-08-01

Energy landscape theories have provided a common ground for understanding the protein folding problem, which once seemed to be overwhelmingly complicated. At the same time, the native state was found to be an ensemble of interconverting states with frustration playing a more important role compared to the folding problem. The landscape of the folded protein - the native landscape - is glassier than the folding landscape; hence, a general description analogous to the folding theories is difficult to achieve. On the other hand, the native basin phase volume is much smaller, allowing a protein to fully sample its native energy landscape on the biological timescales. Current computational resources may also be used to perform this sampling for smaller proteins, to build a 'topographical map' of the native landscape that can be used for subsequent analysis. Several major approaches to representing this topographical map are highlighted in this review, including the construction of kinetic networks, hierarchical trees and free energy surfaces with subsequent structural and kinetic analyses. In this review, we extensively discuss the important question of choosing proper collective coordinates characterizing functional motions. In many cases, the substates on the native energy landscape, which represent different functional states, can be used to obtain variables that are well suited for building free energy surfaces and analyzing the protein's functional dynamics. Normal mode analysis can provide such variables in cases where functional motions are dictated by the molecule's architecture. Principal component analysis is a more expensive way of inferring the essential variables from the protein's motions, one that requires a long molecular dynamics simulation. Finally, the two popular models for the allosteric switching mechanism, 'preexisting equilibrium' and 'induced fit', are interpreted within the energy landscape paradigm as extreme points of a continuum of transition mechanisms. Some experimental evidence illustrating each of these two models, as well as intermediate mechanisms, is presented and discussed.

Treadmill Exercise with Increased Body Loading Enhances Post Flight Functional Performance

NASA Technical Reports Server (NTRS)

Bloomberg, J. J.; Batson, C. D.; Buxton, R. E.; Feiveson, A. H.; Kofman, I. S.; Laurie, S.; Lee, S. M. C.; Miller, C. A.; Mulavara, A. P.; Peters, B. T.;

The importance of functional form in optimal control solutions of problems in population dynamics

USGS Publications Warehouse

Runge, M.C.; Johnson, F.A.

2002-01-01

Optimal control theory is finding increased application in both theoretical and applied ecology, and it is a central element of adaptive resource management. One of the steps in an adaptive management process is to develop alternative models of system dynamics, models that are all reasonable in light of available data, but that differ substantially in their implications for optimal control of the resource. We explored how the form of the recruitment and survival functions in a general population model for ducks affected the patterns in the optimal harvest strategy, using a combination of analytical, numerical, and simulation techniques. We compared three relationships between recruitment and population density (linear, exponential, and hyperbolic) and three relationships between survival during the nonharvest season and population density (constant, logistic, and one related to the compensatory harvest mortality hypothesis). We found that the form of the component functions had a dramatic influence on the optimal harvest strategy and the ultimate equilibrium state of the system. For instance, while it is commonly assumed that a compensatory hypothesis leads to higher optimal harvest rates than an additive hypothesis, we found this to depend on the form of the recruitment function, in part because of differences in the optimal steady-state population density. This work has strong direct consequences for those developing alternative models to describe harvested systems, but it is relevant to a larger class of problems applying optimal control at the population level. Often, different functional forms will not be statistically distinguishable in the range of the data. Nevertheless, differences between the functions outside the range of the data can have an important impact on the optimal harvest strategy. Thus, development of alternative models by identifying a single functional form, then choosing different parameter combinations from extremes on the likelihood profile may end up producing alternatives that do not differ as importantly as if different functional forms had been used. We recommend that biological knowledge be used to bracket a range of possible functional forms, and robustness of conclusions be checked over this range.

Functional imaging of glucose-evoked rat islet activities using transient intrinsic optical signals

NASA Astrophysics Data System (ADS)

Yao, Xin-Cheng; Cui, Wan-Xing; Li, Yi-Chao; Zhang, Wei; Lu, Rong-Wen; Thompson, Anthony; Amthor, Franklin; Wang, Xu-Jing

2012-05-01

We demonstrate intrinsic optical signal (IOS) imaging of intact rat islet, which consists of many endocrine cells working together. A near-infrared digital microscope was employed for optical monitoring of islet activities evoked by glucose stimulation. Dynamic NIR images revealed transient IOS responses in the islet activated by low-dose (2.75 mM) and high-dose (5.5 mM) glucose stimuli. Comparative experiments and quantitative analysis indicated that both glucose metabolism and calcium/insulin dynamics might contribute to the observed IOS responses. Further investigation of the IOS imaging technology may provide a high resolution method for ex vivo functional examination of the islet, which is important for advanced study of diabetes associated islet dysfunctions and for improved quality control of donor islets for transplantation.

The Importance of Engine External's Health

NASA Technical Reports Server (NTRS)

Stoner, Barry L.

2006-01-01

Engine external components include all the fluid carrying, electron carrying, and support devices that are needed to operate the propulsion system. These components are varied and include: pumps, valves, actuators, solenoids, sensors, switches, heat exchangers, electrical generators, electrical harnesses, tubes, ducts, clamps and brackets. The failure of any component to perform its intended function will result in a maintenance action, a dispatch delay, or an engine in flight shutdown. The life of each component, in addition to its basic functional design, is closely tied to its thermal and dynamic environment .Therefore, to reach a mature design life, the component's thermal and dynamic environment must be understood and controlled, which can only be accomplished by attention to design analysis and testing. The purpose of this paper is to review analysis and test techniques toward achieving good component health.

Modeling and stochastic analysis of dynamic mechanisms of the perception

NASA Astrophysics Data System (ADS)

Pisarchik, A.; Bashkirtseva, I.; Ryashko, L.

2017-10-01

Modern studies in physiology and cognitive neuroscience consider a noise as an important constructive factor of the brain functionality. Under the adequate noise, the brain can rapidly access different ordered states, and provide decision-making by preventing deadlocks. Bistable dynamic models are often used for the study of the underlying mechanisms of the visual perception. In the present paper, we consider a bistable energy model subject to both additive and parametric noise. Using the catastrophe theory formalism and stochastic sensitivity functions technique, we analyze a response of the equilibria to noise, and study noise-induced transitions between equilibria. We demonstrate and analyse the effect of hysteresis squeezing when the intensity of noise is increased. Stochastic bifurcations connected with the suppression of oscillations by parametric noises are discussed.

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

Xu, Wenhu; Kotliar, Gabriel; Tsvelik, Alexei M.

Dynamical mean-field theory is used to study the quantum critical point (QCP) in the doped Hubbard model on a square lattice. We characterize the QCP by a universal scaling form of the self-energy and a spin density wave instability at an incommensurate wave vector. The scaling form unifies the low-energy kink and the high-energy waterfall feature in the spectral function, while the spin dynamics includes both the critical incommensurate and high-energy antiferromagnetic paramagnons. Here, we use the frequency-dependent four-point correlation function of spin operators to calculate the momentum-dependent correction to the electron self-energy. Furthermore, by comparing with the calculations basedmore » on the spin-fermion model, our results indicate the frequency dependence of the quasiparticle-paramagnon vertices is an important factor to capture the momentum dependence in quasiparticle scattering.« less

Wave Field Synthesis of moving sources with arbitrary trajectory and velocity profile.

PubMed

Firtha, Gergely; Fiala, Péter

2017-08-01

The sound field synthesis of moving sound sources is of great importance when dynamic virtual sound scenes are to be reconstructed. Previous solutions considered only virtual sources moving uniformly along a straight trajectory, synthesized employing a linear loudspeaker array. This article presents the synthesis of point sources following an arbitrary trajectory. Under high-frequency assumptions 2.5D Wave Field Synthesis driving functions are derived for arbitrary shaped secondary source contours by adapting the stationary phase approximation to the dynamic description of sources in motion. It is explained how a referencing function should be chosen in order to optimize the amplitude of synthesis on an arbitrary receiver curve. Finally, a finite difference implementation scheme is considered, making the presented approach suitable for real-time applications.

Structural and dynamical insight into thermally induced functional inactivation of firefly luciferase

PubMed Central

Jazayeri, Fatemeh S.; Hosseinkhani, Saman

2017-01-01

Luciferase is the key component of light production in bioluminescence process. Extensive and advantageous application of this enzyme in biotechnology is restricted due to its low thermal stability. Here we report the effect of heating up above Tm on the structure and dynamical properties of luciferase enzyme compared to temperature at 298 K. In this way we demonstrate that the number of hydrogen bonds between N- and C-domain is increased for the free enzyme at 325 K. Increased inter domain hydrogen bonds by three at 325 K suggests that inter domain contact is strengthened. The appearance of simultaneous strong salt bridge and hydrogen bond between K529 and D422 and increased existence probability between R533 and E389 could mechanistically explain stronger contact between N- and C-domain. Mutagenesis studies demonstrated the importance of K529 and D422 experimentally. Also the significant reduction in SASA for experimentally important residues K529, D422 and T343 which are involved in active site region was observed. Principle component analysis (PCA) in our study shows that the dynamical behavior of the enzyme is changed upon heating up which mainly originated from the change of motion modes and associated extent of those motions with respect to 298 K. These findings could explain why heating up of the enzyme or thermal fluctuation of protein conformation reduces luciferase activity in course of time as a possible mechanism of thermal functional inactivation. According to these results we proposed two strategies to improve thermal stability of functional luciferase. PMID:28672033

Large-scale Generation of Patterned Bubble Arrays on Printed Bi-functional Boiling Surfaces

PubMed Central

Choi, Chang-Ho; David, Michele; Gao, Zhongwei; Chang, Alvin; Allen, Marshall; Wang, Hailei; Chang, Chih-hung

2016-01-01

Bubble nucleation control, growth and departure dynamics is important in understanding boiling phenomena and enhancing nucleate boiling heat transfer performance. We report a novel bi-functional heterogeneous surface structure that is capable of tuning bubble nucleation, growth and departure dynamics. For the fabrication of the surface, hydrophobic polymer dot arrays are first printed on a substrate, followed by hydrophilic ZnO nanostructure deposition via microreactor-assisted nanomaterial deposition (MAND) processing. Wettability contrast between the hydrophobic polymer dot arrays and aqueous ZnO solution allows for the fabrication of heterogeneous surfaces with distinct wettability regions. Heterogeneous surfaces with various configurations were fabricated and their bubble dynamics were examined at elevated heat flux, revealing various nucleate boiling phenomena. In particular, aligned and patterned bubbles with a tunable departure frequency and diameter were demonstrated in a boiling experiment for the first time. Taking advantage of our fabrication method, a 6 inch wafer size heterogeneous surface was prepared. Pool boiling experiments were also performed to demonstrate a heat flux enhancement up to 3X at the same surface superheat using bi-functional surfaces, compared to a bare stainless steel surface. PMID:27034255

Artificial proteins as allosteric modulators of PDZ3 and SH3 in two-domain constructs: A computational characterization of novel chimeric proteins.

PubMed

Kirubakaran, Palani; Pfeiferová, Lucie; Boušová, Kristýna; Bednarova, Lucie; Obšilová, Veronika; Vondrášek, Jiří

2016-10-01

Artificial multidomain proteins with enhanced structural and functional properties can be utilized in a broad spectrum of applications. The design of chimeric fusion proteins utilizing protein domains or one-domain miniproteins as building blocks is an important advancement for the creation of new biomolecules for biotechnology and medical applications. However, computational studies to describe in detail the dynamics and geometry properties of two-domain constructs made from structurally and functionally different proteins are lacking. Here, we tested an in silico design strategy using all-atom explicit solvent molecular dynamics simulations. The well-characterized PDZ3 and SH3 domains of human zonula occludens (ZO-1) (3TSZ), along with 5 artificial domains and 2 types of molecular linkers, were selected to construct chimeric two-domain molecules. The influence of the artificial domains on the structure and dynamics of the PDZ3 and SH3 domains was determined using a range of analyses. We conclude that the artificial domains can function as allosteric modulators of the PDZ3 and SH3 domains. Proteins 2016; 84:1358-1374. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The axonal transport of mitochondria

PubMed Central

Saxton, William M.; Hollenbeck, Peter J.

2012-01-01

Vigorous transport of cytoplasmic components along axons over substantial distances is crucial for the maintenance of neuron structure and function. The transport of mitochondria, which serves to distribute mitochondrial functions in a dynamic and non-uniform fashion, has attracted special interest in recent years following the discovery of functional connections among microtubules, motor proteins and mitochondria, and their influences on neurodegenerative diseases. Although the motor proteins that drive mitochondrial movement are now well characterized, the mechanisms by which anterograde and retrograde movement are coordinated with one another and with stationary axonal mitochondria are not yet understood. In this Commentary, we review why mitochondria move and how they move, focusing particularly on recent studies of transport regulation, which implicate control of motor activity by specific cell-signaling pathways, regulation of motor access to transport tracks and static microtubule–mitochondrion linkers. A detailed mechanism for modulating anterograde mitochondrial transport has been identified that involves Miro, a mitochondrial Ca2+-binding GTPase, which with associated proteins, can bind and control kinesin-1. Elements of the Miro complex also have important roles in mitochondrial fission–fusion dynamics, highlighting questions about the interdependence of biogenesis, transport, dynamics, maintenance and degradation. PMID:22619228

Nonmonotonicity of the Frictional Bimaterial Effect

NASA Astrophysics Data System (ADS)

Aldam, Michael; Xu, Shiqing; Brener, Efim A.; Ben-Zion, Yehuda; Bouchbinder, Eran

2017-10-01

Sliding along frictional interfaces separating dissimilar elastic materials is qualitatively different from sliding along interfaces separating identical materials due to the existence of an elastodynamic coupling between interfacial slip and normal stress perturbations in the former case. This bimaterial coupling has important implications for the dynamics of frictional interfaces, including their stability and rupture propagation along them. We show that while this bimaterial coupling is a monotonically increasing function of the bimaterial contrast, when it is coupled to interfacial shear stress perturbations through a friction law, various physical quantities exhibit a nonmonotonic dependence on the bimaterial contrast. In particular, we show that for a regularized Coulomb friction, the maximal growth rate of unstable interfacial perturbations of homogeneous sliding is a nonmonotonic function of the bimaterial contrast and provides analytic insight into the origin of this nonmonotonicity. We further show that for velocity-strengthening rate-and-state friction, the maximal growth rate of unstable interfacial perturbations of homogeneous sliding is also a nonmonotonic function of the bimaterial contrast. Results from simulations of dynamic rupture along a bimaterial interface with slip-weakening friction provide evidence that the theoretically predicted nonmonotonicity persists in nonsteady, transient frictional dynamics.

STED microscopy: A simplified method for liver sinusoidal endothelial fenestrae analysis.

PubMed

Martino, Julie Di; Mascalchi, Patrice; Legros, Philippe; Lacomme, Sabrina; Gontier, Etienne; Bioulac-Sage, Paulette; Balabaud, Charles; Moreau, Violaine; Saltel, Frédéric

2018-05-29

Liver sinusoidal endothelial cells (LSECs) possess fenestrae, open transcellular pores with an average diameter of 100nm. These fenestrae allow for the exchange between blood and hepatocytes. Alterations in their number or diameter in liver diseases have important implications for hepatic microcirculation and function. Although decades of studies, fenestrae are still observed into fixed cells and we have poor knowledge of their dynamics. Using stimulated emission depletion (STED) super-resolution microscopy, we have established a faster and simplest method to observe and quantify fenestrae. Indeed, using cytochalasin D, an actin depolymerizing agent known to promote fenestrae formation we measure the increase of fenestrae number. We adapted this methodology to develop an automated method to study fenestrae dynamics. Moreover, with two colors STED analysis we shown that this approach could be useful to study LSECs fenestrae molecular composition. Our approach demonstrate that STED microscopy is suitable for LSEC fenestrae study. This new way of analyzing LSEC fenestrae will allow for expedited investigation of their dynamics, molecular composition and functions to better understand their function in liver pathophysiology. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Evidence of embodied social competence during conversation in high functioning children with autism spectrum disorder

PubMed Central

Fitzpatrick, Paula; Roulier, Stephanie; Duncan, Amie; Richardson, Michael J.; Schmidt, R. C.

2018-01-01

Even high functioning children with Autism Spectrum Disorder (ASD) exhibit impairments that affect their ability to carry out and maintain effective social interactions in multiple contexts. One aspect of subtle nonverbal communication that might play a role in this impairment is the whole-body motor coordination that naturally arises between people during conversation. The current study aimed to measure the time-dependent, coordinated whole-body movements between children with ASD and a clinician during a conversational exchange using tools of nonlinear dynamics. Given the influence that subtle interpersonal coordination has on social interaction feelings, we expected there to be important associations between the dynamic motor movement measures introduced in the current study and the measures used traditionally to categorize ASD impairment (ADOS-2, joint attention and theory of mind). The study found that children with ASD coordinated their bodily movements with a clinician, that these movements were complex and that the complexity of the children’s movements matched that of the clinician’s movements. Importantly, the degree of this bodily coordination was related to higher social cognitive ability. This suggests children with ASD are embodying some degree of social competence during conversations. This study demonstrates the importance of further investigating the subtle but important bodily movement coordination that occurs during social interaction in children with ASD. PMID:29505608

Do glucocorticoids mediate the link between environmental conditions and telomere dynamics in wild vertebrates? A review.

PubMed

Angelier, Frédéric; Costantini, David; Blévin, Pierre; Chastel, Olivier

2018-01-15

Following the discoveries of telomeres and of their implications in terms of health and ageing, there has been a growing interest into the study of telomere dynamics in wild vertebrates. Telomeres are repeated sequences of non-coding DNA located at the terminal ends of chromosomes and they play a major role in maintaining chromosome stability. Importantly, telomeres shorten over time and shorter telomeres seem to be related with lower survival in vertebrates. Because of this potential link with longevity, it is crucial to understand not only the ecological determinants of telomere dynamics but also the regulatory endocrine mechanisms that may mediate the effect of the environment on telomeres. In this paper, we review the relationships that link environmental conditions, glucocorticoids (GC, the main hormonal mediator of allostasis) and telomere length in vertebrates. First, we review current knowledge about the determinants of inter-individual variations in telomere length. We emphasize the potential strong impact of environmental stressors and predictable life-history events on telomere dynamics. Despite recent progress, we still lack crucial basic data to fully understand the costs of several life-history stages and biotic and abiotic factors on telomere length. Second, we review the link that exists between GCs, oxidative stress and telomere dynamics in vertebrates. Although circulating GC levels may be closely and functionally linked with telomere dynamics, data are still scarce and somewhat contradictory. Further laboratory and field studies are therefore needed not only to better assess the proximate link between GC levels and telomere dynamics, but also to ultimately understand to what extent GCs and telomere length could be informative to measure the fitness costs of specific life-history stages and environmental conditions. Finally, we highlight the importance of exploring the functional links that may exist between coping styles, the GC stress response, and telomere dynamics in a life-history framework. To conclude, we raise new hypotheses regarding the potential of the GC stress response to drive the trade-off between immediate survival and telomere protection. Copyright © 2017 Elsevier Inc. All rights reserved.

A Distal Disulfide Bridge in OXA-1 β-Lactamase Stabilizes the Catalytic Center and Alters the Dynamics of the Specificity Determining Ω Loop

DOE PAGES

Simakov, Nikolay; Leonard, David A.; Smith, Jeremy C.; ...

2016-09-26

Widespread antibiotic resistance, particularly when mediated by broad-spectrum β-lactamases, has major implications for public health. Substitutions in the active site often allow broad-spectrum enzymes to accommodate diverse types of β-lactams. Substitutions observed outside the active site are thought to compensate for the loss of thermal stability. The OXA-1 clade of class D β-lactamases contains a pair of conserved cysteines located outside the active site that forms a disulfide bond in the periplasm. In this paper, the effect of the distal disulfide bond on the structure and dynamics of OXA-1 was investigated via 4 μs molecular dynamics simulations. The results revealmore » that the disulfide promotes the preorganized orientation of the catalytic residues and affects the conformation of the functionally important Ω loop. Furthermore, principal component analysis reveals differences in the global dynamics between the oxidized and reduced forms, especially in the motions involving the Ω loop. A dynamical network analysis indicates that, in the oxidized form, in addition to its role in ligand binding, the KTG family motif is a central hub of the global dynamics. Finally, as activity of OXA-1 has been measured only in the reduced form, we suggest that accurate assessment of its functional profile would require oxidative conditions mimicking periplasm.« less

Implicit Self-Importance in an Interpersonal Pronoun Categorization Task

PubMed Central

Fetterman, Adam K.; Robinson, Michael D.; Gilbertson, Elizabeth P.

2014-01-01

Object relations theories emphasize the manner in which the salience/importance of implicit representations of self and other guide interpersonal functioning. Two studies and a pilot test (total N = 304) sought to model such representations. In dyadic contexts, the self is a “you” and the other is a “me”, as verified in a pilot test. Study 1 then used a simple categorization task and found evidence for implicit self-importance: The pronoun “you” was categorized more quickly and accurately when presented in a larger font size, whereas the pronoun “me” was categorized more quickly and accurately when presented in a smaller font size. Study 2 showed that this pattern possesses value in understanding individual differences in interpersonal functioning. As predicted, arrogant people scored higher in implicit self-importance in the paradigm. Findings are discussed from the perspective of dyadic interpersonal dynamics. PMID:25419089

Imaging of Myocardial Fatty Acid Oxidation

PubMed Central

Mather, Kieren J; DeGrado, Tim

2016-01-01

Myocardial fuel selection is a key feature of the health and function of the heart, with clear links between myocardial function and fuel selection and important impacts of fuel selection on ischemia tolerance. Radiopharmaceuticals provide uniquely valuable tools for in vivo, non-invasive assessment of these aspects of cardiac function and metabolism. Here we review the landscape of imaging probes developed to provide noninvasive assessment of myocardial fatty acid oxidation (MFAO). Also, we review the state of current knowledge that myocardial fatty acid imaging has helped establish of static and dynamic fuel selection that characterizes cardiac and cardiometabolic disease and the interplay between fuel selection and various aspects of cardiac function. PMID:26923433

Coupled Modeling of Rhizosphere and Reactive Transport Processes

NASA Astrophysics Data System (ADS)

Roque-Malo, S.; Kumar, P.

2017-12-01

The rhizosphere, as a bio-diverse plant root-soil interface, hosts many hydrologic and biochemical processes, including nutrient cycling, hydraulic redistribution, and soil carbon dynamics among others. The biogeochemical function of root networks, including the facilitation of nutrient cycling through absorption and rhizodeposition, interaction with micro-organisms and fungi, contribution to biomass, etc., plays an important role in myriad Critical Zone processes. Despite this knowledge, the role of the rhizosphere on watershed-scale ecohydrologic functions in the Critical Zone has not been fully characterized, and specifically, the extensive capabilities of reactive transport models (RTMs) have not been applied to these hydrobiogeochemical dynamics. This study uniquely links rhizospheric processes with reactive transport modeling to couple soil biogeochemistry, biological processes, hydrologic flow, hydraulic redistribution, and vegetation dynamics. Key factors in the novel modeling approach are: (i) bi-directional effects of root-soil interaction, such as simultaneous root exudation and nutrient absorption; (ii) multi-state biomass fractions in soil (i.e. living, dormant, and dead biological and root materials); (iii) expression of three-dimensional fluxes to represent both vertical and lateral interconnected flows and processes; and (iv) the potential to include the influence of non-stationary external forcing and climatic factors. We anticipate that the resulting model will demonstrate the extensive effects of plant root dynamics on ecohydrologic functions at the watershed scale and will ultimately contribute to a better characterization of efflux from both agricultural and natural systems.

An Evolutionary Game Theory Model of Spontaneous Brain Functioning.

PubMed

Madeo, Dario; Talarico, Agostino; Pascual-Leone, Alvaro; Mocenni, Chiara; Santarnecchi, Emiliano

2017-11-22

Our brain is a complex system of interconnected regions spontaneously organized into distinct networks. The integration of information between and within these networks is a continuous process that can be observed even when the brain is at rest, i.e. not engaged in any particular task. Moreover, such spontaneous dynamics show predictive value over individual cognitive profile and constitute a potential marker in neurological and psychiatric conditions, making its understanding of fundamental importance in modern neuroscience. Here we present a theoretical and mathematical model based on an extension of evolutionary game theory on networks (EGN), able to capture brain's interregional dynamics by balancing emulative and non-emulative attitudes among brain regions. This results in the net behavior of nodes composing resting-state networks identified using functional magnetic resonance imaging (fMRI), determining their moment-to-moment level of activation and inhibition as expressed by positive and negative shifts in BOLD fMRI signal. By spontaneously generating low-frequency oscillatory behaviors, the EGN model is able to mimic functional connectivity dynamics, approximate fMRI time series on the basis of initial subset of available data, as well as simulate the impact of network lesions and provide evidence of compensation mechanisms across networks. Results suggest evolutionary game theory on networks as a new potential framework for the understanding of human brain network dynamics.

Artificial neural networks for efficient clustering of conformational ensembles and their potential for medicinal chemistry.

PubMed

Pandini, Alessandro; Fraccalvieri, Domenico; Bonati, Laura

2013-01-01

The biological function of proteins is strictly related to their molecular flexibility and dynamics: enzymatic activity, protein-protein interactions, ligand binding and allosteric regulation are important mechanisms involving protein motions. Computational approaches, such as Molecular Dynamics (MD) simulations, are now routinely used to study the intrinsic dynamics of target proteins as well as to complement molecular docking approaches. These methods have also successfully supported the process of rational design and discovery of new drugs. Identification of functionally relevant conformations is a key step in these studies. This is generally done by cluster analysis of the ensemble of structures in the MD trajectory. Recently Artificial Neural Network (ANN) approaches, in particular methods based on Self-Organising Maps (SOMs), have been reported performing more accurately and providing more consistent results than traditional clustering algorithms in various data-mining problems. In the specific case of conformational analysis, SOMs have been successfully used to compare multiple ensembles of protein conformations demonstrating a potential in efficiently detecting the dynamic signatures central to biological function. Moreover, examples of the use of SOMs to address problems relevant to other stages of the drug-design process, including clustering of docking poses, have been reported. In this contribution we review recent applications of ANN algorithms in analysing conformational and structural ensembles and we discuss their potential in computer-based approaches for medicinal chemistry.

Illness beliefs and psychological outcome in people with Parkinson's disease.

PubMed

Simpson, Jane; Lekwuwa, Godwin; Crawford, Trevor

2013-06-01

Illness beliefs are important predictors of psychological outcome in people with chronic illness and evidence suggests these could also be significant in furthering our understanding of psychological functioning in people with Parkinson's disease. Illness beliefs are specific, dynamic representations of an illness and cover dimensions such as cause, identity, consequences and controllability. Eighty-one people with Parkinson's disease completed a series of questionnaires to provide demographic, clinical and psychosocial data, which were then used to assess the relative impact of illness beliefs on their psychological functioning. Psychological functioning was assessed by measuring levels of depression, anxiety, stress, positive affect and emotional well-being. Hierarchical block regression indicated that illness beliefs were important independent predictors across some but not all outcomes and the results emphasised the importance of testing new predictors against more established predictors of outcome such as physical functioning and self-esteem. The illness beliefs most important in psychological outcome in people with PD were causal beliefs (particularly in psychosocial causes) and illness coherence (the level of understanding of the illness). The therapeutic potential of psychosocial variables was discussed given that these can be modified during therapy and this change can positively influence psychological outcome.

Patient-specific CFD simulation of intraventricular haemodynamics based on 3D ultrasound imaging.

PubMed

Bavo, A M; Pouch, A M; Degroote, J; Vierendeels, J; Gorman, J H; Gorman, R C; Segers, P

2016-09-09

The goal of this paper is to present a computational fluid dynamic (CFD) model with moving boundaries to study the intraventricular flows in a patient-specific framework. Starting from the segmentation of real-time transesophageal echocardiographic images, a CFD model including the complete left ventricle and the moving 3D mitral valve was realized. Their motion, known as a function of time from the segmented ultrasound images, was imposed as a boundary condition in an Arbitrary Lagrangian-Eulerian framework. The model allowed for a realistic description of the displacement of the structures of interest and for an effective analysis of the intraventricular flows throughout the cardiac cycle. The model provides detailed intraventricular flow features, and highlights the importance of the 3D valve apparatus for the vortex dynamics and apical flow. The proposed method could describe the haemodynamics of the left ventricle during the cardiac cycle. The methodology might therefore be of particular importance in patient treatment planning to assess the impact of mitral valve treatment on intraventricular flow dynamics.

Ultrafast fluxional exchange dynamics in electrolyte solvation sheath of lithium ion battery

PubMed Central

Lee, Kyung-Koo; Park, Kwanghee; Lee, Hochan; Noh, Yohan; Kossowska, Dorota; Kwak, Kyungwon; Cho, Minhaeng

2017-01-01

Lithium cation is the charge carrier in lithium-ion battery. Electrolyte solution in lithium-ion battery is usually based on mixed solvents consisting of polar carbonates with different aliphatic chains. Despite various experimental evidences indicating that lithium ion forms a rigid and stable solvation sheath through electrostatic interactions with polar carbonates, both the lithium solvation structure and more importantly fluctuation dynamics and functional role of carbonate solvent molecules have not been fully elucidated yet with femtosecond vibrational spectroscopic methods. Here we investigate the ultrafast carbonate solvent exchange dynamics around lithium ions in electrolyte solutions with coherent two-dimensional infrared spectroscopy and find that the time constants of the formation and dissociation of lithium-ion···carbonate complex in solvation sheaths are on a picosecond timescale. We anticipate that such ultrafast microscopic fluxional processes in lithium-solvent complexes could provide an important clue to understanding macroscopic mobility of lithium cation in lithium-ion battery on a molecular level. PMID:28272396

Ultrafast fluxional exchange dynamics in electrolyte solvation sheath of lithium ion battery

NASA Astrophysics Data System (ADS)

Lee, Kyung-Koo; Park, Kwanghee; Lee, Hochan; Noh, Yohan; Kossowska, Dorota; Kwak, Kyungwon; Cho, Minhaeng

2017-03-01

Lithium cation is the charge carrier in lithium-ion battery. Electrolyte solution in lithium-ion battery is usually based on mixed solvents consisting of polar carbonates with different aliphatic chains. Despite various experimental evidences indicating that lithium ion forms a rigid and stable solvation sheath through electrostatic interactions with polar carbonates, both the lithium solvation structure and more importantly fluctuation dynamics and functional role of carbonate solvent molecules have not been fully elucidated yet with femtosecond vibrational spectroscopic methods. Here we investigate the ultrafast carbonate solvent exchange dynamics around lithium ions in electrolyte solutions with coherent two-dimensional infrared spectroscopy and find that the time constants of the formation and dissociation of lithium-ion...carbonate complex in solvation sheaths are on a picosecond timescale. We anticipate that such ultrafast microscopic fluxional processes in lithium-solvent complexes could provide an important clue to understanding macroscopic mobility of lithium cation in lithium-ion battery on a molecular level.

Ultrafast fluxional exchange dynamics in electrolyte solvation sheath of lithium ion battery.

PubMed

Lee, Kyung-Koo; Park, Kwanghee; Lee, Hochan; Noh, Yohan; Kossowska, Dorota; Kwak, Kyungwon; Cho, Minhaeng

2017-03-08

Lithium cation is the charge carrier in lithium-ion battery. Electrolyte solution in lithium-ion battery is usually based on mixed solvents consisting of polar carbonates with different aliphatic chains. Despite various experimental evidences indicating that lithium ion forms a rigid and stable solvation sheath through electrostatic interactions with polar carbonates, both the lithium solvation structure and more importantly fluctuation dynamics and functional role of carbonate solvent molecules have not been fully elucidated yet with femtosecond vibrational spectroscopic methods. Here we investigate the ultrafast carbonate solvent exchange dynamics around lithium ions in electrolyte solutions with coherent two-dimensional infrared spectroscopy and find that the time constants of the formation and dissociation of lithium-ion···carbonate complex in solvation sheaths are on a picosecond timescale. We anticipate that such ultrafast microscopic fluxional processes in lithium-solvent complexes could provide an important clue to understanding macroscopic mobility of lithium cation in lithium-ion battery on a molecular level.

Issues related to the detection of boundaries

Treesearch

M.-J. Fortin; Olson; R.J.; S. Ferson; L. Iverson; C. Hunsaker; G. Edwards; D. Levine; K. Butera; V. Klemas; V. Klemas

2000-01-01

Ecotones are inherent features of landscapes, transitional zones, and play more than one functional role in ecosystem dynamics. The delineation of ecotones and environmental boundaries is therefore an important step in land-use management planning. The delineation of ecotones depends on the phenomenon of interest and the statistical methods used as well as the...

The Impact of Humanities-Based Teaching and Learning Strategies on Critical Thinking and Clinical Reasoning Development among BSN Students

ERIC Educational Resources Information Center

Brodhead, Josette

2016-01-01

The ability to function effectively in a dynamic, culturally diverse healthcare environment requires both critical thinking and clinical reasoning skills. The American Association of Colleges of Nursing (AACN, 2008) recognizes the importance of humanities in the baccalaureate nursing curriculum. This quasi-experimental, nonrandomized…

A phenomenological approach to modeling chemical dynamics in nonlinear and two-dimensional spectroscopy.

PubMed

Ramasesha, Krupa; De Marco, Luigi; Horning, Andrew D; Mandal, Aritra; Tokmakoff, Andrei

2012-04-07

We present an approach for calculating nonlinear spectroscopic observables, which overcomes the approximations inherent to current phenomenological models without requiring the computational cost of performing molecular dynamics simulations. The trajectory mapping method uses the semi-classical approximation to linear and nonlinear response functions, and calculates spectra from trajectories of the system's transition frequencies and transition dipole moments. It rests on identifying dynamical variables important to the problem, treating the dynamics of these variables stochastically, and then generating correlated trajectories of spectroscopic quantities by mapping from the dynamical variables. This approach allows one to describe non-Gaussian dynamics, correlated dynamics between variables of the system, and nonlinear relationships between spectroscopic variables of the system and the bath such as non-Condon effects. We illustrate the approach by applying it to three examples that are often not adequately treated by existing analytical models--the non-Condon effect in the nonlinear infrared spectra of water, non-Gaussian dynamics inherent to strongly hydrogen bonded systems, and chemical exchange processes in barrier crossing reactions. The methods described are generally applicable to nonlinear spectroscopy throughout the optical, infrared and terahertz regions.

Modeling Cytoskeletal Active Matter Systems

NASA Astrophysics Data System (ADS)

Blackwell, Robert

Active networks of filamentous proteins and crosslinking motor proteins play a critical role in many important cellular processes. One of the most important microtubule-motor protein assemblies is the mitotic spindle, a self-organized active liquid-crystalline structure that forms during cell division and that ultimately separates chromosomes into two daughter cells. Although the spindle has been intensively studied for decades, the physical principles that govern its self-organization and function remain mysterious. To evolve a better understanding of spindle formation, structure, and dynamics, I investigate course-grained models of active liquid-crystalline networks composed of microtubules, modeled as hard spherocylinders, in diffusive equilibrium with a reservoir of active crosslinks, modeled as hookean springs that can adsorb to microtubules and and translocate at finite velocity along the microtubule axis. This model is investigated using a combination of brownian dynamics and kinetic monte carlo simulation. I have further refined this model to simulate spindle formation and kinetochore capture in the fission yeast S. pombe. I then make predictions for experimentally realizable perturbations in motor protein presence and function in S. pombe.

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

Krasnobaeva, L. A., E-mail: kla1983@mail.ru; Siberian State Medical University Moscowski Trakt 2, Tomsk, 634050; Shapovalov, A. V.

Within the formalism of the Fokker–Planck equation, the influence of nonstationary external force, random force, and dissipation effects on dynamics local conformational perturbations (kink) propagating along the DNA molecule is investigated. Such waves have an important role in the regulation of important biological processes in living systems at the molecular level. As a dynamic model of DNA was used a modified sine-Gordon equation, simulating the rotational oscillations of bases in one of the chains DNA. The equation of evolution of the kink momentum is obtained in the form of the stochastic differential equation in the Stratonovich sense within the frameworkmore » of the well-known McLaughlin and Scott energy approach. The corresponding Fokker–Planck equation for the momentum distribution function coincides with the equation describing the Ornstein–Uhlenbek process with a regular nonstationary external force. The influence of the nonlinear stochastic effects on the kink dynamics is considered with the help of the Fokker– Planck nonlinear equation with the shift coefficient dependent on the first moment of the kink momentum distribution function. Expressions are derived for average value and variance of the momentum. Examples are considered which demonstrate the influence of the external regular and random forces on the evolution of the average value and variance of the kink momentum. Within the formalism of the Fokker–Planck equation, the influence of nonstationary external force, random force, and dissipation effects on the kink dynamics is investigated in the sine–Gordon model. The equation of evolution of the kink momentum is obtained in the form of the stochastic differential equation in the Stratonovich sense within the framework of the well-known McLaughlin and Scott energy approach. The corresponding Fokker–Planck equation for the momentum distribution function coincides with the equation describing the Ornstein–Uhlenbek process with a regular nonstationary external force. The influence of the nonlinear stochastic effects on the kink dynamics is considered with the help of the Fokker–Planck nonlinear equation with the shift coefficient dependent on the first moment of the kink momentum distribution function. Expressions are derived for average value and variance of the momentum. Examples are considered which demonstrate the influence of the external regular and random forces on the evolution of the average value and variance of the kink momentum.« less

Trichoderma harzianum MTCC 5179 impacts the population and functional dynamics of microbial community in the rhizosphere of black pepper (Piper nigrum L.).

PubMed

Umadevi, Palaniyandi; Anandaraj, Muthuswamy; Srivastav, Vivek; Benjamin, Sailas

2017-11-29

Employing Illumina Hiseq whole genome metagenome sequencing approach, we studied the impact of Trichoderma harzianum on altering the microbial community and its functional dynamics in the rhizhosphere soil of black pepper (Piper nigrum L.). The metagenomic datasets from the rhizosphere with (treatment) and without (control) T. harzianum inoculation were annotated using dual approach, i.e., stand alone and MG-RAST. The probiotic application of T. harzianum in the rhizhosphere soil of black pepper impacted the population dynamics of rhizosphere bacteria, archae, eukaryote as reflected through the selective recruitment of bacteria [Acidobacteriaceae bacterium (p=1.24e-12), Candidatus koribacter versatilis (p=2.66e-10)] and fungi [(Fusarium oxysporum (p=0.013), Talaromyces stipitatus (p=0.219) and Pestalotiopsis fici (p=0.443)] in terms of abundance in population and bacterial chemotaxis (p=0.012), iron metabolism (p=2.97e-5) with the reduction in abundance for pathogenicity islands (p=7.30e-3), phages and prophages (p=7.30e-3) with regard to functional abundance. Interestingly, it was found that the enriched functional metagenomic signatures on phytoremediation such as benzoate transport and degradation (p=2.34e-4), and degradation of heterocyclic aromatic compounds (p=3.59e-13) in the treatment influenced the rhizosphere micro ecosystem favoring growth and health of pepper plant. The population dynamics and functional richness of rhizosphere ecosystem in black pepper influenced by the treatment with T. harzianum provides the ecological importance of T. harzianum in the cultivation of black pepper. Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Dopaminergic modulation of hemodynamic signal variability and the functional connectome during cognitive performance.

PubMed

Alavash, Mohsen; Lim, Sung-Joo; Thiel, Christiane; Sehm, Bernhard; Deserno, Lorenz; Obleser, Jonas

2018-05-15

Dopamine underlies important aspects of cognition, and has been suggested to boost cognitive performance. However, how dopamine modulates the large-scale cortical dynamics during cognitive performance has remained elusive. Using functional MRI during a working memory task in healthy young human listeners, we investigated the effect of levodopa (l-dopa) on two aspects of cortical dynamics, blood oxygen-level-dependent (BOLD) signal variability and the functional connectome of large-scale cortical networks. We here show that enhanced dopaminergic signaling modulates the two potentially interrelated aspects of large-scale cortical dynamics during cognitive performance, and the degree of these modulations is able to explain inter-individual differences in l-dopa-induced behavioral benefits. Relative to placebo, l-dopa increased BOLD signal variability in task-relevant temporal, inferior frontal, parietal and cingulate regions. On the connectome level, however, l-dopa diminished functional integration across temporal and cingulo-opercular regions. This hypo-integration was expressed as a reduction in network efficiency and modularity in more than two thirds of the participants and to different degrees. Hypo-integration co-occurred with relative hyper-connectivity in paracentral lobule and precuneus, as well as posterior putamen. Both, l-dopa-induced BOLD signal variability modulation and functional connectome modulations proved predictive of an individual's l-dopa-induced benefits in behavioral performance, namely response speed and perceptual sensitivity. Lastly, l-dopa-induced modulations of BOLD signal variability were correlated with l-dopa-induced modulation of nodal connectivity and network efficiency. Our findings underline the role of dopamine in maintaining the dynamic range of, and communication between, cortical systems, and their explanatory power for inter-individual differences in benefits from dopamine during cognitive performance. Copyright © 2018 Elsevier Inc. All rights reserved.

Changing contributions of stochastic and deterministic processes in community assembly over a successional gradient.

PubMed

Måren, Inger Elisabeth; Kapfer, Jutta; Aarrestad, Per Arild; Grytnes, John-Arvid; Vandvik, Vigdis

2018-01-01

Successional dynamics in plant community assembly may result from both deterministic and stochastic ecological processes. The relative importance of different ecological processes is expected to vary over the successional sequence, between different plant functional groups, and with the disturbance levels and land-use management regimes of the successional systems. We evaluate the relative importance of stochastic and deterministic processes in bryophyte and vascular plant community assembly after fire in grazed and ungrazed anthropogenic coastal heathlands in Northern Europe. A replicated series of post-fire successions (n = 12) were initiated under grazed and ungrazed conditions, and vegetation data were recorded in permanent plots over 13 years. We used redundancy analysis (RDA) to test for deterministic successional patterns in species composition repeated across the replicate successional series and analyses of co-occurrence to evaluate to what extent species respond synchronously along the successional gradient. Change in species co-occurrences over succession indicates stochastic successional dynamics at the species level (i.e., species equivalence), whereas constancy in co-occurrence indicates deterministic dynamics (successional niche differentiation). The RDA shows high and deterministic vascular plant community compositional change, especially early in succession. Co-occurrence analyses indicate stochastic species-level dynamics the first two years, which then give way to more deterministic replacements. Grazed and ungrazed successions are similar, but the early stage stochasticity is higher in ungrazed areas. Bryophyte communities in ungrazed successions resemble vascular plant communities. In contrast, bryophytes in grazed successions showed consistently high stochasticity and low determinism in both community composition and species co-occurrence. In conclusion, stochastic and individualistic species responses early in succession give way to more niche-driven dynamics in later successional stages. Grazing reduces predictability in both successional trends and species-level dynamics, especially in plant functional groups that are not well adapted to disturbance. © 2017 The Authors. Ecology, published by Wiley Periodicals, Inc., on behalf of the Ecological Society of America.

A dynamic structural model of expanded RNA CAG repeats: A refined X-ray structure and computational investigations using molecular dynamics and umbrella sampling simulations

PubMed Central

Yildirim, Ilyas; Park, Hajeung; Disney, Matthew D.; Schatz, George C.

2013-01-01

One class of functionally important RNA is repeating transcripts that cause disease through various mechanisms. For example, expanded r(CAG) repeats can cause Huntington’s and other disease through translation of toxic proteins. Herein, crystal structure of r[5ʹUUGGGC(CAG)3GUCC]2, a model of CAG expanded transcripts, refined to 1.65 Å resolution is disclosed that show both anti-anti and syn-anti orientations for 1×1 nucleotide AA internal loops. Molecular dynamics (MD) simulations using Amber force field in explicit solvent were run for over 500 ns on model systems r(5ʹGCGCAGCGC)2 (MS1) and r(5ʹCCGCAGCGG)2 (MS2). In these MD simulations, both anti-anti and syn-anti AA base pairs appear to be stable. While anti-anti AA base pairs were dynamic and sampled multiple anti-anti conformations, no syn-anti↔anti-anti transformations were observed. Umbrella sampling simulations were run on MS2, and a 2D free energy surface was created to extract transformation pathways. In addition, over 800 ns explicit solvent MD simulation was run on r[5ʹGGGC(CAG)3GUCC]2, which closely represents the refined crystal structure. One of the terminal AA base pairs (syn-anti conformation), transformed to anti-anti conformation. The pathway followed in this transformation was the one predicted by umbrella sampling simulations. Further analysis showed a binding pocket near AA base pairs in syn-anti conformations. Computational results combined with the refined crystal structure show that global minimum conformation of 1×1 nucleotide AA internal loops in r(CAG) repeats is anti-anti but can adopt syn-anti depending on the environment. These results are important to understand RNA dynamic-function relationships and develop small molecules that target RNA dynamic ensembles. PMID:23441937

Mori-Zwanzig theory for dissipative forces in coarse-grained dynamics in the Markov limit

NASA Astrophysics Data System (ADS)

Izvekov, Sergei

2017-01-01

We derive alternative Markov approximations for the projected (stochastic) force and memory function in the coarse-grained (CG) generalized Langevin equation, which describes the time evolution of the center-of-mass coordinates of clusters of particles in the microscopic ensemble. This is done with the aid of the Mori-Zwanzig projection operator method based on the recently introduced projection operator [S. Izvekov, J. Chem. Phys. 138, 134106 (2013), 10.1063/1.4795091]. The derivation exploits the "generalized additive fluctuating force" representation to which the projected force reduces in the adopted projection operator formalism. For the projected force, we present a first-order time expansion which correctly extends the static fluctuating force ansatz with the terms necessary to maintain the required orthogonality of the projected dynamics in the Markov limit to the space of CG phase variables. The approximant of the memory function correctly accounts for the momentum dependence in the lowest (second) order and indicates that such a dependence may be important in the CG dynamics approaching the Markov limit. In the case of CG dynamics with a weak dependence of the memory effects on the particle momenta, the expression for the memory function presented in this work is applicable to non-Markov systems. The approximations are formulated in a propagator-free form allowing their efficient evaluation from the microscopic data sampled by standard molecular dynamics simulations. A numerical application is presented for a molecular liquid (nitromethane). With our formalism we do not observe the "plateau-value problem" if the friction tensors for dissipative particle dynamics (DPD) are computed using the Green-Kubo relation. Our formalism provides a consistent bottom-up route for hierarchical parametrization of DPD models from atomistic simulations.

Power law scaling in synchronization of brain signals depends on cognitive load.

PubMed

Tinker, Jesse; Velazquez, Jose Luis Perez

2014-01-01

As it has several features that optimize information processing, it has been proposed that criticality governs the dynamics of nervous system activity. Indications of such dynamics have been reported for a variety of in vitro and in vivo recordings, ranging from in vitro slice electrophysiology to human functional magnetic resonance imaging. However, there still remains considerable debate as to whether the brain actually operates close to criticality or in another governing state such as stochastic or oscillatory dynamics. A tool used to investigate the criticality of nervous system data is the inspection of power-law distributions. Although the findings are controversial, such power-law scaling has been found in different types of recordings. Here, we studied whether there is a power law scaling in the distribution of the phase synchronization derived from magnetoencephalographic recordings during executive function tasks performed by children with and without autism. Characterizing the brain dynamics that is different between autistic and non-autistic individuals is important in order to find differences that could either aid diagnosis or provide insights as to possible therapeutic interventions in autism. We report in this study that power law scaling in the distributions of a phase synchrony index is not very common and its frequency of occurrence is similar in the control and the autism group. In addition, power law scaling tends to diminish with increased cognitive load (difficulty or engagement in the task). There were indications of changes in the probability distribution functions for the phase synchrony that were associated with a transition from power law scaling to lack of power law (or vice versa), which suggests the presence of phenomenological bifurcations in brain dynamics associated with cognitive load. Hence, brain dynamics may fluctuate between criticality and other regimes depending upon context and behaviors.

Next Generation Extended Lagrangian Quantum-based Molecular Dynamics

NASA Astrophysics Data System (ADS)

Negre, Christian

2017-06-01

A new framework for extended Lagrangian first-principles molecular dynamics simulations is presented, which overcomes shortcomings of regular, direct Born-Oppenheimer molecular dynamics, while maintaining important advantages of the unified extended Lagrangian formulation of density functional theory pioneered by Car and Parrinello three decades ago. The new framework allows, for the first time, energy conserving, linear-scaling Born-Oppenheimer molecular dynamics simulations, which is necessary to study larger and more realistic systems over longer simulation times than previously possible. Expensive, self-consinstent-field optimizations are avoided and normal integration time steps of regular, direct Born-Oppenheimer molecular dynamics can be used. Linear scaling electronic structure theory is presented using a graph-based approach that is ideal for parallel calculations on hybrid computer platforms. For the first time, quantum based Born-Oppenheimer molecular dynamics simulation is becoming a practically feasible approach in simulations of +100,000 atoms-representing a competitive alternative to classical polarizable force field methods. In collaboration with: Anders Niklasson, Los Alamos National Laboratory.

Complex collective dynamics of active torque-driven colloids at interfaces

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

Snezhko, Alexey

Modern self-assembly techniques aiming to produce complex structural order or functional diversity often rely on non-equilibrium conditions in the system. Light, electric, or magnetic fields are predominantly used to modify interaction profiles of colloidal particles during self-assembly or induce complex out-of-equilibrium dynamic ordering. The energy injection rate, properties of the environment are important control parameters that influence the outcome of active (dynamic) self-assembly. The current review is focused on a case of collective dynamics and self-assembly of particles with externally driven torques coupled to a liquid or solid interface. The complexity of interactions in such systems is further enriched bymore » strong hydrodynamic coupling between particles. Unconventionally ordered dynamic self-assembled patterns, spontaneous symmetry breaking phenomena, self-propulsion, and collective transport have been reported in torque-driven colloids. Some of the features of the complex collective behavior and dynamic pattern formation in those active systems have been successfully captured in simulations.« less

Sequence, Structural Analysis and Metrics to Define the Unique Dynamic Features of the Flap Regions Among Aspartic Proteases.

PubMed

McGillewie, Lara; Ramesh, Muthusamy; Soliman, Mahmoud E

2017-10-01

Aspartic proteases are a class of hydrolytic enzymes that have been implicated in a number of diseases such as HIV, malaria, cancer and Alzheimer's. The flap region of aspartic proteases is a characteristic unique structural feature of these enzymes; and found to have a profound impact on protein overall structure, function and dynamics. Flap dynamics also plays a crucial role in drug binding and drug resistance. Therefore, understanding the structure and dynamic behavior of this flap regions is crucial in the design of potent and selective inhibitors against aspartic proteases. Defining metrics that can describe the flap motion/dynamics has been a challenging topic in literature. This review is the first attempt to compile comprehensive information on sequence, structure, motion and metrics used to assess the dynamics of the flap region of different aspartic proteases in "one pot". We believe that this review would be of critical importance to the researchers from different scientific domains.

Zipping and Unzipping of Adenylate Kinase: Atomistic Insights into the Ensemble of Open ↔ Closed Transitions

PubMed Central

Beckstein, Oliver; Denning, Elizabeth J.; Perilla, Juan R.; Woolf, Thomas B.

2009-01-01

Adenylate kinase (AdK), a phosphotransferase enzyme, plays an important role in cellular energy homeostasis. It undergoes a large conformational change between an open and a closed state, even in the absence of substrate. We investigate the apo-AdK transition at the atomic level both with free energy calculations and our new dynamic importance sampling (DIMS) molecular dynamics (MD) method. DIMS is shown to sample biologically relevant conformations as verified by comparing an ensemble of hundreds of DIMS transitions to AdK crystal structure intermediates. The simulations reveal in atomic detail how hinge regions partially and intermittently unfold during the transition. Conserved salt bridges are seen to have important structural and dynamic roles; in particular four ionic bonds are identified that open in a sequential, zipper-like fashion and thus dominate the free energy landscape of the transition. Transitions between the closed and open conformations only have to overcome moderate free energy barriers. Unexpectedly, the closed and open state encompass broad free energy basins that contain conformations differing in domain hinge motions by up to 40°. The significance of these extended states is discussed in relation to recent experimental FRET measurements. Taken together, these results demonstrate how a small number of cooperative key interactions can shape the overall dynamics of an enzyme and suggest an “all-or-nothing” mechanism for the opening and closing of AdK. Our efficient DIMS-MD computer simulation approach can provide a detailed picture of a functionally important macromolecular transition and thus help to interpret and suggest experiments to probe the conformational landscape of dynamic proteins such as AdK. PMID:19751742

Discovering governing equations from data by sparse identification of nonlinear dynamics

NASA Astrophysics Data System (ADS)

Brunton, Steven

The ability to discover physical laws and governing equations from data is one of humankind's greatest intellectual achievements. A quantitative understanding of dynamic constraints and balances in nature has facilitated rapid development of knowledge and enabled advanced technology, including aircraft, combustion engines, satellites, and electrical power. There are many more critical data-driven problems, such as understanding cognition from neural recordings, inferring patterns in climate, determining stability of financial markets, predicting and suppressing the spread of disease, and controlling turbulence for greener transportation and energy. With abundant data and elusive laws, data-driven discovery of dynamics will continue to play an increasingly important role in these efforts. This work develops a general framework to discover the governing equations underlying a dynamical system simply from data measurements, leveraging advances in sparsity-promoting techniques and machine learning. The resulting models are parsimonious, balancing model complexity with descriptive ability while avoiding overfitting. The only assumption about the structure of the model is that there are only a few important terms that govern the dynamics, so that the equations are sparse in the space of possible functions. This perspective, combining dynamical systems with machine learning and sparse sensing, is explored with the overarching goal of real-time closed-loop feedback control of complex systems. This is joint work with Joshua L. Proctor and J. Nathan Kutz. Video Abstract: https://www.youtube.com/watch?v=gSCa78TIldg

Multi-scale volumetric cell and tissue imaging based on optical projection tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Ban, Sungbea; Cho, Nam Hyun; Ryu, Yongjae; Jung, Sunwoo; Vavilin, Andrey; Min, Eunjung; Jung, Woonggyu

2016-04-01

Optical projection tomography is a new optical imaging method for visualizing small biological specimens in three dimension. The most important advantage of OPT is to fill the gap between MRI and confocal microscope for the specimen having the range of 1-10 mm. Thus, it has been mainly used for whole-mount small animals and developmental study since this imaging modality was developed. The ability of OPT delivering anatomical and functional information of relatively large tissue in 3D has made it a promising platform in biomedical research. Recently, the potential of OPT spans its coverage to cellular scale. Even though there are increasing demand to obtain better understanding of cellular dynamics, only few studies to visualize cellular structure, shape, size and functional morphology over tissue has been investigated in existing OPT system due to its limited field of view. In this study, we develop a novel optical imaging system for 3D cellular imaging with OPT integrated with dynamic focusing technique. Our tomographic setup has great potential to be used for identifying cell characteristic in tissue because it can provide selective contrast on dynamic focal plane allowing for fluorescence as well as absorption. While the dominant contrast of optical imaging technique is to use the fluorescence for detecting certain target only, the newly developed OPT system will offer considerable advantages over currently available method when imaging cellar molecular dynamics by permitting contrast variation. By achieving multi-contrast, it is expected for this new imaging system to play an important role in delivering better cytological information to pathologist.

Comparison of the dynamics of substrate access channels in three cytochrome P450s reveals different opening mechanisms and a novel functional role for a buried arginine

PubMed Central

Winn, Peter J.; Lüdemann, Susanna K.; Gauges, Ralph; Lounnas, Valère; Wade, Rebecca C.

2002-01-01

Understanding the mechanism and specificity of substrate binding in the cytochrome P450 (P450) superfamily is an important step toward explaining its key role in drug metabolism, toxicity, xenobiotic degradation, and several biosynthetic pathways. Here we investigate the ligand exit pathways and mechanisms of P450cam (CYP101), P450BM-3 (CYP102), and P450eryF (CYP107A1) by using random expulsion molecular dynamics and classical molecular dynamics simulations. Although several different pathways are found for each protein, one pathway is common to all three. The mechanism of ligand exit along this pathway is, however, quite different in the three different proteins. For P450cam, small backbone conformational changes, in combination with aromatic side chain rotation, allow for the passage of the rather rigid, compact, and hydrophobic substrate, camphor. In P450BM-3, larger transient backbone changes are observed on ligand exit. R47, situated at the entrance to the channel, appears important in guiding negatively charged fatty acid substrates in and out of the active site. In P450eryF, an isolated buried arginine, R185, stabilized by four hydrogen bonds to backbone carbonyl oxygen atoms, is located in the exit channel and is identified as having a particularly unusual functionality, dynamically gating channel opening. The results for these three P450s suggest that the channel opening mechanisms are adjusted to the physico-chemical properties of the substrate and can kinetically modulate protein-substrate specificity. PMID:11959989

Predicting Changes in Arctic Tundra Vegetation: Towards an Understanding of Plant Trait Uncertainty

NASA Astrophysics Data System (ADS)

Euskirchen, E. S.; Serbin, S.; Carman, T.; Iversen, C. M.; Salmon, V.; Helene, G.; McGuire, A. D.

2017-12-01

Arctic tundra plant communities are currently undergoing unprecedented changes in both composition and distribution under a warming climate. Predicting how these dynamics may play out in the future is important since these vegetation shifts impact both biogeochemical and biogeophysical processes. More precise estimates of these future vegetation shifts is a key challenge due to both a scarcity of data with which to parameterize vegetation models, particularly in the Arctic, as well as a limited understanding of the importance of each of the model parameters and how they may vary over space and time. Here, we incorporate newly available field data from arctic Alaska into a dynamic vegetation model specifically developed to take into account a particularly wide array of plant species as well as the permafrost soils of the arctic tundra (the Terrestrial Ecosystem Model with Dynamic Vegetation and Dynamic Organic Soil, Terrestrial Ecosystem Model; DVM-DOS-TEM). We integrate the model within the Predicative Ecosystem Analyzer (PEcAn), an open-source integrated ecological bioinformatics toolbox that facilitates the flows of information into and out of process models and model-data integration. We use PEcAn to evaluate the plant functional traits that contribute most to model variability based on a sensitivity analysis. We perform this analysis for the dominant types of tundra in arctic Alaska, including heath, shrub, tussock and wet sedge tundra. The results from this analysis will help inform future data collection in arctic tundra and reduce model uncertainty, thereby improving our ability to simulate Arctic vegetation structure and function in response to global change.

Growth-rate-dependent dynamics of a bacterial genetic oscillator

NASA Astrophysics Data System (ADS)

Osella, Matteo; Lagomarsino, Marco Cosentino

2013-01-01

Gene networks exhibiting oscillatory dynamics are widespread in biology. The minimal regulatory designs giving rise to oscillations have been implemented synthetically and studied by mathematical modeling. However, most of the available analyses generally neglect the coupling of regulatory circuits with the cellular “chassis” in which the circuits are embedded. For example, the intracellular macromolecular composition of fast-growing bacteria changes with growth rate. As a consequence, important parameters of gene expression, such as ribosome concentration or cell volume, are growth-rate dependent, ultimately coupling the dynamics of genetic circuits with cell physiology. This work addresses the effects of growth rate on the dynamics of a paradigmatic example of genetic oscillator, the repressilator. Making use of empirical growth-rate dependencies of parameters in bacteria, we show that the repressilator dynamics can switch between oscillations and convergence to a fixed point depending on the cellular state of growth, and thus on the nutrients it is fed. The physical support of the circuit (type of plasmid or gene positions on the chromosome) also plays an important role in determining the oscillation stability and the growth-rate dependence of period and amplitude. This analysis has potential application in the field of synthetic biology, and suggests that the coupling between endogenous genetic oscillators and cell physiology can have substantial consequences for their functionality.

A dynamic interaction process between KaiA and KaiC is critical to the cyanobacterial circadian oscillator.

PubMed

Dong, Pei; Fan, Ying; Sun, Jianqiang; Lv, Mengting; Yi, Ming; Tan, Xiao; Liu, Sen

2016-04-26

The core circadian oscillator of cyanobacteria consists of three proteins, KaiA, KaiB, and KaiC. This circadian oscillator could be functionally reconstituted in vitro with these three proteins, and therefore has been a very important model in circadian rhythm research. KaiA can bind to KaiC and then stimulate its phosphorylation, but their interaction mechanism remains elusive. In this study, we followed the "second-site suppressor" strategy to investigate the interaction mechanism of KaiA and KaiC. Using protein sequence analyses, we showed that there exist co-varying residues in the binding interface of KaiA and KaiC. The followed mutagenesis study verified that these residues are important to the functions of KaiA and KaiC, but their roles could not be fully explained by the reported complex structures of KaiA and KaiC derived peptides. Combining our data with previous reports, we suggested a dynamic interaction mechanism in KaiA-KaiC interaction, in which both KaiA and the intrinsically disordered tail of KaiC undergo significant structural changes through conformational selection and induced fit during the binding process. At last, we presented a mathematic model to support this hypothesis and explained the importance of this interaction mechanism for the KaiABC circadian oscillator.

Transmission dynamics: critical questions and challenges

PubMed Central

2017-01-01

This article overviews the dynamics of disease transmission in one-host–one-parasite systems. Transmission is the result of interacting host and pathogen processes, encapsulated with the environment in a ‘transmission triangle’. Multiple transmission modes and their epidemiological consequences are often not understood because the direct measurement of transmission is difficult. However, its different components can be analysed using nonlinear transmission functions, contact matrices and networks. A particular challenge is to develop such functions for spatially extended systems. This is illustrated for vector transmission where a ‘perception kernel’ approach is developed that incorporates vector behaviour in response to host spacing. A major challenge is understanding the relative merits of the large number of approaches to quantifying transmission. The evolution of transmission mode itself has been a rather neglected topic, but is important in the context of understanding disease emergence and genetic variation in pathogens. Disease impacts many biological processes such as community stability, the evolution of sex and speciation, yet the importance of different transmission modes in these processes is not understood. Broader approaches and ideas to disease transmission are important in the public health realm for combating newly emerging infections. This article is part of the themed issue ‘Opening the black box: re-examining the ecology and evolution of parasite transmission’. PMID:28289255

A dynamic interaction process between KaiA and KaiC is critical to the cyanobacterial circadian oscillator

NASA Astrophysics Data System (ADS)

Dong, Pei; Fan, Ying; Sun, Jianqiang; Lv, Mengting; Yi, Ming; Tan, Xiao; Liu, Sen

2016-04-01

The core circadian oscillator of cyanobacteria consists of three proteins, KaiA, KaiB, and KaiC. This circadian oscillator could be functionally reconstituted in vitro with these three proteins, and therefore has been a very important model in circadian rhythm research. KaiA can bind to KaiC and then stimulate its phosphorylation, but their interaction mechanism remains elusive. In this study, we followed the “second-site suppressor” strategy to investigate the interaction mechanism of KaiA and KaiC. Using protein sequence analyses, we showed that there exist co-varying residues in the binding interface of KaiA and KaiC. The followed mutagenesis study verified that these residues are important to the functions of KaiA and KaiC, but their roles could not be fully explained by the reported complex structures of KaiA and KaiC derived peptides. Combining our data with previous reports, we suggested a dynamic interaction mechanism in KaiA-KaiC interaction, in which both KaiA and the intrinsically disordered tail of KaiC undergo significant structural changes through conformational selection and induced fit during the binding process. At last, we presented a mathematic model to support this hypothesis and explained the importance of this interaction mechanism for the KaiABC circadian oscillator.

Structural and dynamic properties of the C-terminal region of the Escherichia coli RNA chaperone Hfq: integrative experimental and computational studies.

PubMed

Wen, Bin; Wang, Weiwei; Zhang, Jiahai; Gong, Qingguo; Shi, Yunyu; Wu, Jihui; Zhang, Zhiyong

2017-08-09

In Escherichia coli, hexameric Hfq is an important RNA chaperone that facilitates small RNA-mediated post-transcriptional regulation. The Hfq monomer consists of an evolutionarily conserved Sm domain (residues 1-65) and a flexible C-terminal region (residues 66-102). It has been recognized that the existence of the C-terminal region is important for the function of Hfq, but its detailed structural and dynamic properties remain elusive due to its disordered nature. In this work, using integrative experimental techniques, such as nuclear magnetic resonance spectroscopy and small-angle X-ray scattering, as well as multi-scale computational simulations, new insights into the structure and dynamics of the C-terminal region in the context of the Hfq hexamer are provided. Although the C-terminal region is intrinsically disordered, some residues (83-86) are motionally restricted. The hexameric core may affect the secondary structure propensity of the C-terminal region, due to transient interactions between them. The residues at the rim and the proximal side of the core have significantly more transient contacts with the C-terminal region than those residues at the distal side, which may facilitate the function of the C-terminal region in the release of double-stranded RNAs and the cycling of small non-coding RNAs. Structure ensembles constructed by fitting the experimental data also support that the C-terminal region prefers to locate at the proximal side. From multi-scale simulations, we propose that the C-terminal region may play a dual role of steric effect (especially at the proximal side) and recruitment (at the both sides) in the binding process of RNA substrates. Interestingly, we have found that these motionally restricted residues may serve as important binding sites for the incoming RNAs that is probably driven by favorable electrostatic interactions. These integrative studies may aid in our understanding of the functional role of the C-terminal region of Hfq.

The physiological basis and clinical significance of lung volume measurements.

PubMed

Lutfi, Mohamed Faisal

2017-01-01

From a physiological standpoint, the lung volumes are either dynamic or static. Both subclasses are measured at different degrees of inspiration or expiration; however, dynamic lung volumes are characteristically dependent on the rate of air flow. The static lung volumes/capacities are further subdivided into four standard volumes (tidal, inspiratory reserve, expiratory reserve, and residual volumes) and four standard capacities (inspiratory, functional residual, vital and total lung capacities). The dynamic lung volumes are mostly derived from vital capacity. While dynamic lung volumes are essential for diagnosis and follow up of obstructive lung diseases, static lung volumes are equally important for evaluation of obstructive as well as restrictive ventilatory defects. This review intends to update the reader with the physiological basis, clinical significance and interpretative approaches of the standard static lung volumes and capacities.

Molecular dynamics simulations of membrane proteins and their interactions: from nanoscale to mesoscale.

PubMed

Chavent, Matthieu; Duncan, Anna L; Sansom, Mark Sp

2016-10-01

Molecular dynamics simulations provide a computational tool to probe membrane proteins and systems at length scales ranging from nanometers to close to a micrometer, and on microsecond timescales. All atom and coarse-grained simulations may be used to explore in detail the interactions of membrane proteins and specific lipids, yielding predictions of lipid binding sites in good agreement with available structural data. Building on the success of protein-lipid interaction simulations, larger scale simulations reveal crowding and clustering of proteins, resulting in slow and anomalous diffusional dynamics, within realistic models of cell membranes. Current methods allow near atomic resolution simulations of small membrane organelles, and of enveloped viruses to be performed, revealing key aspects of their structure and functionally important dynamics. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Trajectory-based nonadiabatic dynamics with time-dependent density functional theory.

PubMed

Curchod, Basile F E; Rothlisberger, Ursula; Tavernelli, Ivano

2013-05-10

Understanding the fate of an electronically excited molecule constitutes an important task for theoretical chemistry, and practical implications range from the interpretation of atto- and femtosecond spectroscopy to the development of light-driven molecular machines, the control of photochemical reactions, and the possibility of capturing sunlight energy. However, many challenging conceptual and technical problems are involved in the description of these phenomena such as 1) the failure of the well-known Born-Oppenheimer approximation; 2) the need for accurate electronic properties such as potential energy surfaces, excited nuclear forces, or nonadiabatic coupling terms; and 3) the necessity of describing the dynamics of the photoexcited nuclear wavepacket. This review provides an overview of the current methods to address points 1) and 3) and shows how time-dependent density functional theory (TDDFT) and its linear-response extension can be used for point 2). First, the derivation of Ehrenfest dynamics and nonadiabatic Bohmian dynamics is discussed and linked to Tully's trajectory surface hopping. Second, the coupling of these trajectory-based nonadiabatic schemes with TDDFT is described in detail with special emphasis on the derivation of the required electronic structure properties. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Vision-based flight control in the hawkmoth Hyles lineata

PubMed Central

Windsor, Shane P.; Bomphrey, Richard J.; Taylor, Graham K.

2014-01-01

Vision is a key sensory modality for flying insects, playing an important role in guidance, navigation and control. Here, we use a virtual-reality flight simulator to measure the optomotor responses of the hawkmoth Hyles lineata, and use a published linear-time invariant model of the flight dynamics to interpret the function of the measured responses in flight stabilization and control. We recorded the forces and moments produced during oscillation of the visual field in roll, pitch and yaw, varying the temporal frequency, amplitude or spatial frequency of the stimulus. The moths’ responses were strongly dependent upon contrast frequency, as expected if the optomotor system uses correlation-type motion detectors to sense self-motion. The flight dynamics model predicts that roll angle feedback is needed to stabilize the lateral dynamics, and that a combination of pitch angle and pitch rate feedback is most effective in stabilizing the longitudinal dynamics. The moths’ responses to roll and pitch stimuli coincided qualitatively with these functional predictions. The moths produced coupled roll and yaw moments in response to yaw stimuli, which could help to reduce the energetic cost of correcting heading. Our results emphasize the close relationship between physics and physiology in the stabilization of insect flight. PMID:24335557

A microcomputer-based testing station for dynamic and static testing of protective relay systems

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

Lee, W.J.; Li, R.J.; Gu, J.C.

1995-12-31

Dynamic and static relay performance testing before installation in the field is a subject of great interest to utility relay engineers. The common practice in utility testing of new relays is to put the new unit to be tested in parallel with an existing functioning relay in the system, wait until an actual transient occurs and then observe and analyze the performance of new relay. It is impossible to have a thorough test of the protective relay system through this procedure. An equipment, Microcomputer-Based Testing Station (or PC-Based Testing Station), that can perform both static and dynamic testing of themore » relay is described in this paper. The Power System Simulation Laboratory at the University of Texas at Arlington is a scaled-down, three-phase, physical power system which correlates well with the important components for a real power system and is an ideal facility for the dynamic and static testing of protective relay systems. A brief introduction to the configuration of this laboratory is presented. Test results of several protective functions by using this laboratory illustrate the usefulness of this test set-up.« less

Foam Optics and Mechanics

NASA Technical Reports Server (NTRS)

Durian, Douglas J.; Zimmerli, Gregory A.

2002-01-01

The Foam Optics and Mechanics (FOAM) project will exploit the microgravity environment to more accurately measure the rheological and optical characteristics of wet aqueous foams. Using both rheology and laser light scattering diagnostics, the goal is to quantify the unusual elastic character of foams in terms of their underlying microscopic structure and dynamics. Of particular interest is determining how the elastic character vanishes, i.e., how the foam 'melts' into a simple viscous liquid, as a function of both increasing liquid content and increasing shear strain rate. The unusual elastic character of foams will be quantified macroscopically by measurement of the shear stress as a function of shear strain rate and of time following a step strain. Such data will be analyzed in terms of a yield stress, shear moduli, and dynamical time scales. Microscopic information about bubble packing and rearrangement dynamics, from which the macroscopic non-Newtonian properties ultimately arise, will be obtained non-invasively by multiple-light scattering: diffuse transmission spectroscopy (DTS) and diffusing wave spectroscopy (DWS). Quantitative trends with materials parameters, most importantly average bubble size and liquid content, will be sought in order to elucidate the fundamental connection between the microscopic structure and dynamics and the macroscopic rheology.

Global identification of stochastic dynamical systems under different pseudo-static operating conditions: The functionally pooled ARMAX case

NASA Astrophysics Data System (ADS)

Sakellariou, J. S.; Fassois, S. D.

2017-01-01

The identification of a single global model for a stochastic dynamical system operating under various conditions is considered. Each operating condition is assumed to have a pseudo-static effect on the dynamics and be characterized by a single measurable scheduling variable. Identification is accomplished within a recently introduced Functionally Pooled (FP) framework, which offers a number of advantages over Linear Parameter Varying (LPV) identification techniques. The focus of the work is on the extension of the framework to include the important FP-ARMAX model case. Compared to their simpler FP-ARX counterparts, FP-ARMAX models are much more general and offer improved flexibility in describing various types of stochastic noise, but at the same time lead to a more complicated, non-quadratic, estimation problem. Prediction Error (PE), Maximum Likelihood (ML), and multi-stage estimation methods are postulated, and the PE estimator optimality, in terms of consistency and asymptotic efficiency, is analytically established. The postulated estimators are numerically assessed via Monte Carlo experiments, while the effectiveness of the approach and its superiority over its FP-ARX counterpart are demonstrated via an application case study pertaining to simulated railway vehicle suspension dynamics under various mass loading conditions.