Transfer function verification and block diagram simplification of a very high-order distributed pole closed-loop servo by means of non-linear time-response simulation

NASA Technical Reports Server (NTRS)

Mukhopadhyay, A. K.

1975-01-01

Linear frequency domain methods are inadequate in analyzing the 1975 Viking Orbiter (VO75) digital tape recorder servo due to dominant nonlinear effects such as servo signal limiting, unidirectional servo control, and static/dynamic Coulomb friction. The frequency loop (speed control) servo of the VO75 tape recorder is used to illustrate the analytical tools and methodology of system redundancy elimination and high order transfer function verification. The paper compares time-domain performance parameters derived from a series of nonlinear time responses with the available experimental data in order to select the best possible analytical transfer function representation of the tape transport (mechanical segment of the tape recorder) from several possible candidates. The study also shows how an analytical time-response simulation taking into account most system nonlinearities can pinpoint system redundancy and overdesign stemming from a strictly empirical design approach. System order reduction is achieved through truncation of individual transfer functions and elimination of redundant blocks.

Statistical Time Series Models of Pilot Control with Applications to Instrument Discrimination

NASA Technical Reports Server (NTRS)

Altschul, R. E.; Nagel, P. M.; Oliver, F.

1984-01-01

A general description of the methodology used in obtaining the transfer function models and verification of model fidelity, frequency domain plots of the modeled transfer functions, numerical results obtained from an analysis of poles and zeroes obtained from z plane to s-plane conversions of the transfer functions, and the results of a study on the sequential introduction of other variables, both exogenous and endogenous into the loop are contained.

Estimation of Handling Qualities Parameters of the Tu-144 Supersonic Transport Aircraft from Flight Test Data

NASA Technical Reports Server (NTRS)

Curry, Timothy J.; Batterson, James G. (Technical Monitor)

2000-01-01

Low order equivalent system (LOES) models for the Tu-144 supersonic transport aircraft were identified from flight test data. The mathematical models were given in terms of transfer functions with a time delay by the military standard MIL-STD-1797A, "Flying Qualities of Piloted Aircraft," and the handling qualities were predicted from the estimated transfer function coefficients. The coefficients and the time delay in the transfer functions were estimated using a nonlinear equation error formulation in the frequency domain. Flight test data from pitch, roll, and yaw frequency sweeps at various flight conditions were used for parameter estimation. Flight test results are presented in terms of the estimated parameter values, their standard errors, and output fits in the time domain. Data from doublet maneuvers at the same flight conditions were used to assess the predictive capabilities of the identified models. The identified transfer function models fit the measured data well and demonstrated good prediction capabilities. The Tu-144 was predicted to be between level 2 and 3 for all longitudinal maneuvers and level I for all lateral maneuvers. High estimates of the equivalent time delay in the transfer function model caused the poor longitudinal rating.

Curved Displacement Transfer Functions for Geometric Nonlinear Large Deformation Structure Shape Predictions

NASA Technical Reports Server (NTRS)

Ko, William L.; Fleischer, Van Tran; Lung, Shun-Fat

2017-01-01

For shape predictions of structures under large geometrically nonlinear deformations, Curved Displacement Transfer Functions were formulated based on a curved displacement, traced by a material point from the undeformed position to deformed position. The embedded beam (depth-wise cross section of a structure along a surface strain-sensing line) was discretized into multiple small domains, with domain junctures matching the strain-sensing stations. Thus, the surface strain distribution could be described with a piecewise linear or a piecewise nonlinear function. The discretization approach enabled piecewise integrations of the embedded-beam curvature equations to yield the Curved Displacement Transfer Functions, expressed in terms of embedded beam geometrical parameters and surface strains. By entering the surface strain data into the Displacement Transfer Functions, deflections along each embedded beam can be calculated at multiple points for mapping the overall structural deformed shapes. Finite-element linear and nonlinear analyses of a tapered cantilever tubular beam were performed to generate linear and nonlinear surface strains and the associated deflections to be used for validation. The shape prediction accuracies were then determined by comparing the theoretical deflections with the finiteelement- generated deflections. The results show that the newly developed Curved Displacement Transfer Functions are very accurate for shape predictions of structures under large geometrically nonlinear deformations.

Effect of membrane microheterogeneity and domain size on fluorescence resonance energy transfer.

PubMed

Towles, Kevin B; Brown, Angela C; Wrenn, Steven P; Dan, Nily

2007-07-15

Studies of multicomponent membranes suggest lateral inhomogeneity in the form of membrane domains, but the size of small (nanoscale) domains in situ cannot be determined with current techniques. In this article, we present a model that enables extraction of membrane domain size from time-resolved fluorescence resonance energy transfer (FRET) data. We expand upon a classic approach to the infinite phase separation limit and formulate a model that accounts for the presence of disklike domains of finite dimensions within a two-dimensional infinite planar bilayer. The model was tested against off-lattice Monte Carlo calculations of a model membrane in the liquid-disordered (l(d)) and liquid-ordered (l(o)) coexistence regime. Simulated domain size was varied from 5 to 50 nm, and two fluorophores, preferentially partitioning into opposite phases, were randomly mixed to obtain the simulated time-resolved FRET data. The Monte Carlo data show clear differences in the efficiency of energy transfer as a function of domain size. The model fit of the data yielded good agreement for the domain size, especially in cases where the domain diameter is <20 nm. Thus, data analysis using the proposed model enables measurement of nanoscale membrane domains using time-resolved FRET.

The Relation of Self Variables to Transfer Student Success as Measured by Academic, Psychological, and Career Functioning

ERIC Educational Resources Information Center

Ling, Thomson Joseph

2006-01-01

Research has suggested that transfer students experience difficulty in many domains however limited research has examined the variables associated with transfer student success. The present study examined transfer student success using a sample of 163 first-year transfer students at a large mid-Atlantic university. The mean age of the participants…

Concomitant prediction of function and fold at the domain level with GO-based profiles.

PubMed

Lopez, Daniel; Pazos, Florencio

2013-01-01

Predicting the function of newly sequenced proteins is crucial due to the pace at which these raw sequences are being obtained. Almost all resources for predicting protein function assign functional terms to whole chains, and do not distinguish which particular domain is responsible for the allocated function. This is not a limitation of the methodologies themselves but it is due to the fact that in the databases of functional annotations these methods use for transferring functional terms to new proteins, these annotations are done on a whole-chain basis. Nevertheless, domains are the basic evolutionary and often functional units of proteins. In many cases, the domains of a protein chain have distinct molecular functions, independent from each other. For that reason resources with functional annotations at the domain level, as well as methodologies for predicting function for individual domains adapted to these resources are required.We present a methodology for predicting the molecular function of individual domains, based on a previously developed database of functional annotations at the domain level. The approach, which we show outperforms a standard method based on sequence searches in assigning function, concomitantly predicts the structural fold of the domains and can give hints on the functionally important residues associated to the predicted function.

Semantic layers for illustrative volume rendering.

PubMed

Rautek, Peter; Bruckner, Stefan; Gröller, Eduard

2007-01-01

Direct volume rendering techniques map volumetric attributes (e.g., density, gradient magnitude, etc.) to visual styles. Commonly this mapping is specified by a transfer function. The specification of transfer functions is a complex task and requires expert knowledge about the underlying rendering technique. In the case of multiple volumetric attributes and multiple visual styles the specification of the multi-dimensional transfer function becomes more challenging and non-intuitive. We present a novel methodology for the specification of a mapping from several volumetric attributes to multiple illustrative visual styles. We introduce semantic layers that allow a domain expert to specify the mapping in the natural language of the domain. A semantic layer defines the mapping of volumetric attributes to one visual style. Volumetric attributes and visual styles are represented as fuzzy sets. The mapping is specified by rules that are evaluated with fuzzy logic arithmetics. The user specifies the fuzzy sets and the rules without special knowledge about the underlying rendering technique. Semantic layers allow for a linguistic specification of the mapping from attributes to visual styles replacing the traditional transfer function specification.

Using frequency-domain methods to identify XV-15 aeroelastic modes

NASA Technical Reports Server (NTRS)

Acree, C. W., Jr.; Tischler, Mark B.

1987-01-01

The XV-15 Tilt-Rotor wing has six major aeroelastic modes that are close in frequency. To precisely excite individual modes during flight test, dual flaperon exciters with automatic frequency-sweep controls were installed. The resulting structural data were analyzed in the frequency domain (Fourier transformed) with cross spectral and transfer function methods. Modal frequencies and damping were determined by performing curve fits to transfer function magnitude and phase data and to cross spectral magnitude data. Results are given for the XV-15 with its original metal rotor blades. Frequency and damping values are also compared with earlier predictions.

Analysis of the transfer function for layered piezoelectric ultrasonic sensors

NASA Astrophysics Data System (ADS)

Gutiérrrez-Reyes, E.; García-Segundo, C.; García-Valenzuela, A.; Reyes-Ramírez, B.; Gutiérrez-Juárez, G.; Guadarrama-Santana, A.

2017-06-01

We model theoretically the voltage response to an acoustic pulse of a multilayer system forming a low noise capacitive sensor including a Polyvinylidene Fluoride piezoelectric film. First we model a generic piezoelectric detector consisting of a piezoelectric film between two metallic electrodes that are the responsible to convert the acoustic signal into a voltage signal. Then we calculate the pressure-to-voltage transfer function for a N-layer piezo-electric capacitor detector, allowing to study the effects of the electrode and protective layers thickness in typical layered piezoelectric sensors. The derived transfer function, when multiplied by the Fourier transform of the incident acoustic pulse, gives the voltage electric response in the frequency domain. An important concern regarding the transfer function is that it may have zeros at specific frequencies, and thus inverting the voltage Fourier transform of the pulse to recover the pressure signal in the time domain is not always, in principle, possible. Our formulas can be used to predict the existence and locations of such zeroes. We illustrate the use of the transfer function by predicting the electric signal generated at a multilayer piezoelectric sensor to an ultrasonic pulse generated photoacoustically by a laser pulse at a three media system with impedance mismatch. This theoretical calculations are compared with our own experimental measurements.

Extensive domain motion and electron transfer in the human electron transferring flavoprotein.medium chain Acyl-CoA dehydrogenase complex.

PubMed

Toogood, Helen S; van Thiel, Adam; Basran, Jaswir; Sutcliffe, Mike J; Scrutton, Nigel S; Leys, David

2004-07-30

The crystal structure of the human electron transferring flavoprotein (ETF).medium chain acyl-CoA dehydrogenase (MCAD) complex reveals a dual mode of protein-protein interaction, imparting both specificity and promiscuity in the interaction of ETF with a range of structurally distinct primary dehydrogenases. ETF partitions the functions of partner binding and electron transfer between (i) the recognition loop, which acts as a static anchor at the ETF.MCAD interface, and (ii) the highly mobile redox active FAD domain. Together, these enable the FAD domain of ETF to sample a range of conformations, some compatible with fast interprotein electron transfer. Disorders in amino acid or fatty acid catabolism can be attributed to mutations at the protein-protein interface. Crucially, complex formation triggers mobility of the FAD domain, an induced disorder that contrasts with general models of protein-protein interaction by induced fit mechanisms. The subsequent interfacial motion in the MCAD.ETF complex is the basis for the interaction of ETF with structurally diverse protein partners. Solution studies using ETF and MCAD with mutations at the protein-protein interface support this dynamic model and indicate ionic interactions between MCAD Glu(212) and ETF Arg alpha(249) are likely to transiently stabilize productive conformations of the FAD domain leading to enhanced electron transfer rates between both partners.

Improved block copolymer domain dispersity on chemical patterns via homopolymer-blending and molecular transfer printing

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

Liu, Guoliang; Nealey, Paul F.

Herein we have investigated the domain width distributions of block copolymers and their ternary blends after directed assembly on chemically patterned surfaces with and without density multiplication. On chemical patterns with density multiplication, the width of the interpolated block copolymer domains was bimodal. Once blended with the corresponding homopolymers, the block copolymers exhibited unimodal distributions of domain width due to the redistribution of homopolymers in the block copolymer domains. When the block copolymers were blended with hydroxyl-terminated homopolymers, the homopolymers with functional end-groups healed the chemical patterns and facilitated the formation of nanostructures with further improved domain width distributions. Lastly,more » it is demonstrated that the block copolymers achieved the most improved domain width distributions when directed to assemble without density multiplication on one-to-one chemical patterns generated by molecular transfer printing.« less

Atmospheric Turbulence Modeling for Aero Vehicles: Fractional Order Fits

NASA Technical Reports Server (NTRS)

Kopasakis, George

2015-01-01

Atmospheric turbulence models are necessary for the design of both inlet/engine and flight controls, as well as for studying coupling between the propulsion and the vehicle structural dynamics for supersonic vehicles. Models based on the Kolmogorov spectrum have been previously utilized to model atmospheric turbulence. In this paper, a more accurate model is developed in its representative fractional order form, typical of atmospheric disturbances. This is accomplished by first scaling the Kolmogorov spectral to convert them into finite energy von Karman forms and then by deriving an explicit fractional circuit-filter type analog for this model. This circuit model is utilized to develop a generalized formulation in frequency domain to approximate the fractional order with the products of first order transfer functions, which enables accurate time domain simulations. The objective of this work is as follows. Given the parameters describing the conditions of atmospheric disturbances, and utilizing the derived formulations, directly compute the transfer function poles and zeros describing these disturbances for acoustic velocity, temperature, pressure, and density. Time domain simulations of representative atmospheric turbulence can then be developed by utilizing these computed transfer functions together with the disturbance frequencies of interest.

Atmospheric Turbulence Modeling for Aero Vehicles: Fractional Order Fits

NASA Technical Reports Server (NTRS)

Kopasakis, George

2010-01-01

Atmospheric turbulence models are necessary for the design of both inlet/engine and flight controls, as well as for studying coupling between the propulsion and the vehicle structural dynamics for supersonic vehicles. Models based on the Kolmogorov spectrum have been previously utilized to model atmospheric turbulence. In this paper, a more accurate model is developed in its representative fractional order form, typical of atmospheric disturbances. This is accomplished by first scaling the Kolmogorov spectral to convert them into finite energy von Karman forms and then by deriving an explicit fractional circuit-filter type analog for this model. This circuit model is utilized to develop a generalized formulation in frequency domain to approximate the fractional order with the products of first order transfer functions, which enables accurate time domain simulations. The objective of this work is as follows. Given the parameters describing the conditions of atmospheric disturbances, and utilizing the derived formulations, directly compute the transfer function poles and zeros describing these disturbances for acoustic velocity, temperature, pressure, and density. Time domain simulations of representative atmospheric turbulence can then be developed by utilizing these computed transfer functions together with the disturbance frequencies of interest.

Generalised Transfer Functions of Neural Networks

NASA Astrophysics Data System (ADS)

Fung, C. F.; Billings, S. A.; Zhang, H.

1997-11-01

When artificial neural networks are used to model non-linear dynamical systems, the system structure which can be extremely useful for analysis and design, is buried within the network architecture. In this paper, explicit expressions for the frequency response or generalised transfer functions of both feedforward and recurrent neural networks are derived in terms of the network weights. The derivation of the algorithm is established on the basis of the Taylor series expansion of the activation functions used in a particular neural network. This leads to a representation which is equivalent to the non-linear recursive polynomial model and enables the derivation of the transfer functions to be based on the harmonic expansion method. By mapping the neural network into the frequency domain information about the structure of the underlying non-linear system can be recovered. Numerical examples are included to demonstrate the application of the new algorithm. These examples show that the frequency response functions appear to be highly sensitive to the network topology and training, and that the time domain properties fail to reveal deficiencies in the trained network structure.

Structural basis of sterol recognition and nonvesicular transport by lipid transfer proteins anchored at membrane contact sites.

PubMed

Tong, Junsen; Manik, Mohammad Kawsar; Im, Young Jun

2018-01-30

Membrane contact sites (MCSs) in eukaryotic cells are hotspots for lipid exchange, which is essential for many biological functions, including regulation of membrane properties and protein trafficking. Lipid transfer proteins anchored at membrane contact sites (LAMs) contain sterol-specific lipid transfer domains [StARkin domain (SD)] and multiple targeting modules to specific membrane organelles. Elucidating the structural mechanisms of targeting and ligand recognition by LAMs is important for understanding the interorganelle communication and exchange at MCSs. Here, we determined the crystal structures of the yeast Lam6 pleckstrin homology (PH)-like domain and the SDs of Lam2 and Lam4 in the apo form and in complex with ergosterol. The Lam6 PH-like domain displays a unique PH domain fold with a conserved N-terminal α-helix. The Lam6 PH-like domain lacks the basic surface for phosphoinositide binding, but contains hydrophobic patches on its surface, which are critical for targeting to endoplasmic reticulum (ER)-mitochondrial contacts. Structures of the LAM SDs display a helix-grip fold with a hydrophobic cavity and a flexible Ω1-loop as a lid. Ergosterol is bound to the pocket in a head-down orientation, with its hydrophobic acyl group located in the tunnel entrance. The Ω1-loop in an open conformation is essential for ergosterol binding by direct hydrophobic interaction. Structural comparison suggested that the sterol binding mode of the Lam2 SD2 is likely conserved among the sterol transfer proteins of the StARkin superfamily. Structural models of full-length Lam2 correlated with the sterol transport function at the membrane contact sites.

Transfer of control system interface solutions from other domains to the thermal power industry.

PubMed

Bligård, L-O; Andersson, J; Osvalder, A-L

2012-01-01

In a thermal power plant the operators' roles are to control and monitor the process to achieve efficient and safe production. To achieve this, the human-machine interfaces have a central part. The interfaces need to be updated and upgraded together with the technical functionality to maintain optimal operation. One way of achieving relevant updates is to study other domains and see how they have solved similar issues in their design solutions. The purpose of this paper is to present how interface design solution ideas can be transferred from domains with operator control to thermal power plants. In the study 15 domains were compared using a model for categorisation of human-machine systems. The result from the domain comparison showed that nuclear power, refinery and ship engine control were most similar to thermal power control. From the findings a basic interface structure and three specific display solutions were proposed for thermal power control: process parameter overview, plant overview, and feed water view. The systematic comparison of the properties of a human-machine system allowed interface designers to find suitable objects, structures and navigation logics in a range of domains that could be transferred to the thermal power domain.

Dynamic gas temperature measurement system. Volume 2: Operation and program manual

NASA Technical Reports Server (NTRS)

Purpura, P. T.

1983-01-01

The hot section technology (HOST) dynamic gas temperature measurement system computer program acquires data from two type B thermocouples of different diameters. The analysis method determines the in situ value of an aerodynamic parameter T, containing the heat transfer coefficient from the transfer function of the two thermocouples. This aerodynamic parameter is used to compute a fequency response spectrum and compensate the dynamic portion of the signal of the smaller thermocouple. The calculations for the aerodynamic parameter and the data compensation technique are discussed. Compensated data are presented in either the time or frequency domain, time domain data as dynamic temperature vs time, or frequency domain data.

Wavelet Analyses of F/A-18 Aeroelastic and Aeroservoelastic Flight Test Data

NASA Technical Reports Server (NTRS)

Brenner, Martin J.

1997-01-01

Time-frequency signal representations combined with subspace identification methods were used to analyze aeroelastic flight data from the F/A-18 Systems Research Aircraft (SRA) and aeroservoelastic data from the F/A-18 High Alpha Research Vehicle (HARV). The F/A-18 SRA data were produced from a wingtip excitation system that generated linear frequency chirps and logarithmic sweeps. HARV data were acquired from digital Schroeder-phased and sinc pulse excitation signals to actuator commands. Nondilated continuous Morlet wavelets implemented as a filter bank were chosen for the time-frequency analysis to eliminate phase distortion as it occurs with sliding window discrete Fourier transform techniques. Wavelet coefficients were filtered to reduce effects of noise and nonlinear distortions identically in all inputs and outputs. Cleaned reconstructed time domain signals were used to compute improved transfer functions. Time and frequency domain subspace identification methods were applied to enhanced reconstructed time domain data and improved transfer functions, respectively. Time domain subspace performed poorly, even with the enhanced data, compared with frequency domain techniques. A frequency domain subspace method is shown to produce better results with the data processed using the Morlet time-frequency technique.

The 32nd CDC: System identification using interval dynamic models

NASA Technical Reports Server (NTRS)

Keel, L. H.; Lew, J. S.; Bhattacharyya, S. P.

1992-01-01

Motivated by the recent explosive development of results in the area of parametric robust control, a new technique to identify a family of uncertain systems is identified. The new technique takes the frequency domain input and output data obtained from experimental test signals and produces an 'interval transfer function' that contains the complete frequency domain behavior with respect to the test signals. This interval transfer function is one of the key concepts in the parametric robust control approach and identification with such an interval model allows one to predict the worst case performance and stability margins using recent results on interval systems. The algorithm is illustrated by applying it to an 18 bay Mini-Mast truss structure.

Computer program for single input-output, single-loop feedback systems

NASA Technical Reports Server (NTRS)

1976-01-01

Additional work is reported on a completely automatic computer program for the design of single input/output, single loop feedback systems with parameter uncertainly, to satisfy time domain bounds on the system response to step commands and disturbances. The inputs to the program are basically the specified time-domain response bounds, the form of the constrained plant transfer function and the ranges of the uncertain parameters of the plant. The program output consists of the transfer functions of the two free compensation networks, in the form of the coefficients of the numerator and denominator polynomials, and the data on the prescribed bounds and the extremes actually obtained for the system response to commands and disturbances.

Comprehensive analysis of orthologous protein domains using the HOPS database.

PubMed

Storm, Christian E V; Sonnhammer, Erik L L

2003-10-01

One of the most reliable methods for protein function annotation is to transfer experimentally known functions from orthologous proteins in other organisms. Most methods for identifying orthologs operate on a subset of organisms with a completely sequenced genome, and treat proteins as single-domain units. However, it is well known that proteins are often made up of several independent domains, and there is a wealth of protein sequences from genomes that are not completely sequenced. A comprehensive set of protein domain families is found in the Pfam database. We wanted to apply orthology detection to Pfam families, but first some issues needed to be addressed. First, orthology detection becomes impractical and unreliable when too many species are included. Second, shorter domains contain less information. It is therefore important to assess the quality of the orthology assignment and avoid very short domains altogether. We present a database of orthologous protein domains in Pfam called HOPS: Hierarchical grouping of Orthologous and Paralogous Sequences. Orthology is inferred in a hierarchic system of phylogenetic subgroups using ortholog bootstrapping. To avoid the frequent errors stemming from horizontally transferred genes in bacteria, the analysis is presently limited to eukaryotic genes. The results are accessible in the graphical browser NIFAS, a Java tool originally developed for analyzing phylogenetic relations within Pfam families. The method was tested on a set of curated orthologs with experimentally verified function. In comparison to tree reconciliation with a complete species tree, our approach finds significantly more orthologs in the test set. Examples for investigating gene fusions and domain recombination using HOPS are given.

Genomic analysis of bifunctional Class C-Class D β-lactamases in environmental bacteria.

PubMed

Silveira, Melise Chaves; Catanho, Marcos; Miranda, Antônio Basílio de

2018-01-01

β-lactamases, which are found in several bacterial species and environments, are the main cause of resistance to β-lactams in Gram-negative bacteria. In 2009, a protein (LRA-13) with two β-lactamase domains (one class C domain and one class D domain) was experimentally characterised, and an extended action spectrum against β-lactams consistent with two functional domains was found. Here, we present the results of searches in the non-redundant NCBI protein database that revealed the existence of a group of homologous bifunctional β-lactamases in the genomes of environmental bacteria. These findings suggest that bifunctional β-lactamases are widespread in nature; these findings also raise concern that bifunctional β-lactamases may be transferred to bacteria of clinical importance through lateral gene transfer mechanisms.

Policy Transfer via Markov Logic Networks

NASA Astrophysics Data System (ADS)

Torrey, Lisa; Shavlik, Jude

We propose using a statistical-relational model, the Markov Logic Network, for knowledge transfer in reinforcement learning. Our goal is to extract relational knowledge from a source task and use it to speed up learning in a related target task. We show that Markov Logic Networks are effective models for capturing both source-task Q-functions and source-task policies. We apply them via demonstration, which involves using them for decision making in an initial stage of the target task before continuing to learn. Through experiments in the RoboCup simulated-soccer domain, we show that transfer via Markov Logic Networks can significantly improve early performance in complex tasks, and that transferring policies is more effective than transferring Q-functions.

Fast computation of the electrolyte-concentration transfer function of a lithium-ion cell model

NASA Astrophysics Data System (ADS)

Rodríguez, Albert; Plett, Gregory L.; Trimboli, M. Scott

2017-08-01

One approach to creating physics-based reduced-order models (ROMs) of battery-cell dynamics requires first generating linearized Laplace-domain transfer functions of all cell internal electrochemical variables of interest. Then, the resulting infinite-dimensional transfer functions can be reduced by various means in order to find an approximate low-dimensional model. These methods include Padé approximation or the Discrete-Time Realization algorithm. In a previous article, Lee and colleagues developed a transfer function of the electrolyte concentration for a porous-electrode pseudo-two-dimensional lithium-ion cell model. Their approach used separation of variables and Sturm-Liouville theory to compute an infinite-series solution to the transfer function, which they then truncated to a finite number of terms for reasons of practicality. Here, we instead use a variation-of-parameters approach to arrive at a different representation of the identical solution that does not require a series expansion. The primary benefits of the new approach are speed of computation of the transfer function and the removal of the requirement to approximate the transfer function by truncating the number of terms evaluated. Results show that the speedup of the new method can be more than 3800.

The transfer functions of cardiac tissue during stochastic pacing.

PubMed

de Lange, Enno; Kucera, Jan P

2009-01-01

The restitution properties of cardiac action potential duration (APD) and conduction velocity (CV) are important factors in arrhythmogenesis. They determine alternans, wavebreak, and the patterns of reentrant arrhythmias. We developed a novel approach to characterize restitution using transfer functions. Transfer functions relate an input and an output quantity in terms of gain and phase shift in the complex frequency domain. We derived an analytical expression for the transfer function of interbeat intervals (IBIs) during conduction from one site (input) to another site downstream (output). Transfer functions can be efficiently obtained using a stochastic pacing protocol. Using simulations of conduction and extracellular mapping of strands of neonatal rat ventricular myocytes, we show that transfer functions permit the quantification of APD and CV restitution slopes when it is difficult to measure APD directly. We find that the normally positive CV restitution slope attenuates IBI variations. In contrast, a negative CV restitution slope (induced by decreasing extracellular [K(+)]) amplifies IBI variations with a maximum at the frequency of alternans. Hence, it potentiates alternans and renders conduction unstable, even in the absence of APD restitution. Thus, stochastic pacing and transfer function analysis represent a powerful strategy to evaluate restitution and the stability of conduction.

Measurement techniques for the characterization in the frequency domain of regulated energy-storage DC-to-DC converters. M.S. Thesis

NASA Technical Reports Server (NTRS)

Bahler, D. D.

1978-01-01

Procedures are presented for obtaining valid frequency-domain transfer functions of regulated reactor energy-storage dc-to-dc converters. These procedures are for measuring loop gain, closed loop gain, output impedance, and audio susceptibility. The applications of these measurements are discussed.

Online Heterogeneous Transfer by Hedge Ensemble of Offline and Online Decisions.

PubMed

Yan, Yuguang; Wu, Qingyao; Tan, Mingkui; Ng, Michael K; Min, Huaqing; Tsang, Ivor W

2017-10-10

In this paper, we study the online heterogeneous transfer (OHT) learning problem, where the target data of interest arrive in an online manner, while the source data and auxiliary co-occurrence data are from offline sources and can be easily annotated. OHT is very challenging, since the feature spaces of the source and target domains are different. To address this, we propose a novel technique called OHT by hedge ensemble by exploiting both offline knowledge and online knowledge of different domains. To this end, we build an offline decision function based on a heterogeneous similarity that is constructed using labeled source data and unlabeled auxiliary co-occurrence data. After that, an online decision function is learned from the target data. Last, we employ a hedge weighting strategy to combine the offline and online decision functions to exploit knowledge from the source and target domains of different feature spaces. We also provide a theoretical analysis regarding the mistake bounds of the proposed approach. Comprehensive experiments on three real-world data sets demonstrate the effectiveness of the proposed technique.

Correspondence Search Mitigation Using Feature Space Anti-Aliasing

DTIC Science & Technology

2007-01-01

trackers are widely used in astro -inertial nav- igation systems for long-range aircraft, space navigation, and ICBM guidance. When ground images are to be...frequency domain representation of the point spread function, H( fx , fy), is called the optical transfer function. Applying the Fourier transform to the...frequency domain representation of the image: I( fx , fy, t) = O( fx , fy, t)H( fx , fy) (4) In most conditions, the projected scene can be treated as a

Horizontal functional gene transfer from bacteria to fishes.

PubMed

Sun, Bao-Fa; Li, Tong; Xiao, Jin-Hua; Jia, Ling-Yi; Liu, Li; Zhang, Peng; Murphy, Robert W; He, Shun-Min; Huang, Da-Wei

2015-12-22

Invertebrates can acquire functional genes via horizontal gene transfer (HGT) from bacteria but fishes are not known to do so. We provide the first reliable evidence of one HGT event from marine bacteria to fishes. The HGT appears to have occurred after emergence of the teleosts. The transferred gene is expressed and regulated developmentally. Its successful integration and expression may change the genetic and metabolic repertoire of fishes. In addition, this gene contains conserved domains and similar tertiary structures in fishes and their putative donor bacteria. Thus, it may function similarly in both groups. Evolutionary analyses indicate that it evolved under purifying selection, further indicating its conserved function. We document the first likely case of HGT of functional gene from prokaryote to fishes. This discovery certifies that HGT can influence vertebrate evolution.

Modeling procedures for handling qualities evaluation of flexible aircraft

NASA Technical Reports Server (NTRS)

Govindaraj, K. S.; Eulrich, B. J.; Chalk, C. R.

1981-01-01

This paper presents simplified modeling procedures to evaluate the impact of flexible modes and the unsteady aerodynamic effects on the handling qualities of Supersonic Cruise Aircraft (SCR). The modeling procedures involve obtaining reduced order transfer function models of SCR vehicles, including the important flexible mode responses and unsteady aerodynamic effects, and conversion of the transfer function models to time domain equations for use in simulations. The use of the modeling procedures is illustrated by a simple example.

An Autoinhibitory Role for the Pleckstrin Homology Domain of Interleukin-2-Inducible Tyrosine Kinase and Its Interplay with Canonical Phospholipid Recognition.

PubMed

Devkota, Sujan; Joseph, Raji E; Boyken, Scott E; Fulton, D Bruce; Andreotti, Amy H

2017-06-13

Pleckstrin homology (PH) domains are well-known as phospholipid binding modules, yet evidence that PH domain function extends beyond lipid recognition is mounting. In this work, we characterize a protein binding function for the PH domain of interleukin-2-inducible tyrosine kinase (ITK), an immune cell specific signaling protein that belongs to the TEC family of nonreceptor tyrosine kinases. Its N-terminal PH domain is a well-characterized lipid binding module that localizes ITK to the membrane via phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ) binding. Using a combination of nuclear magnetic resonance spectroscopy and mutagenesis, we have mapped an autoregulatory protein interaction site on the ITK PH domain that makes direct contact with the catalytic kinase domain of ITK, inhibiting the phospho-transfer reaction. Moreover, we have elucidated an important interplay between lipid binding by the ITK PH domain and the stability of the autoinhibitory complex formed by full length ITK. The ITK activation loop in the kinase domain becomes accessible to phosphorylation to the exogenous kinase LCK upon binding of the ITK PH domain to PIP 3 . By clarifying the allosteric role of the ITK PH domain in controlling ITK function, we have expanded the functional repertoire of the PH domain generally and opened the door to alternative strategies to target this specific kinase in the context of immune cell signaling.

Domain architecture conservation in orthologs

PubMed Central

2011-01-01

Background As orthologous proteins are expected to retain function more often than other homologs, they are often used for functional annotation transfer between species. However, ortholog identification methods do not take into account changes in domain architecture, which are likely to modify a protein's function. By domain architecture we refer to the sequential arrangement of domains along a protein sequence. To assess the level of domain architecture conservation among orthologs, we carried out a large-scale study of such events between human and 40 other species spanning the entire evolutionary range. We designed a score to measure domain architecture similarity and used it to analyze differences in domain architecture conservation between orthologs and paralogs relative to the conservation of primary sequence. We also statistically characterized the extents of different types of domain swapping events across pairs of orthologs and paralogs. Results The analysis shows that orthologs exhibit greater domain architecture conservation than paralogous homologs, even when differences in average sequence divergence are compensated for, for homologs that have diverged beyond a certain threshold. We interpret this as an indication of a stronger selective pressure on orthologs than paralogs to retain the domain architecture required for the proteins to perform a specific function. In general, orthologs as well as the closest paralogous homologs have very similar domain architectures, even at large evolutionary separation. The most common domain architecture changes observed in both ortholog and paralog pairs involved insertion/deletion of new domains, while domain shuffling and segment duplication/deletion were very infrequent. Conclusions On the whole, our results support the hypothesis that function conservation between orthologs demands higher domain architecture conservation than other types of homologs, relative to primary sequence conservation. This supports the notion that orthologs are functionally more similar than other types of homologs at the same evolutionary distance. PMID:21819573

Group refractive index quantification using a Fourier domain short coherence Sagnac interferometer.

PubMed

Montonen, Risto; Kassamakov, Ivan; Lehmann, Peter; Österberg, Kenneth; Hæggström, Edward

2018-02-15

The group refractive index is important in length calibration of Fourier domain interferometers by transparent transfer standards. We demonstrate accurate group refractive index quantification using a Fourier domain short coherence Sagnac interferometer. Because of a justified linear length calibration function, the calibration constants cancel out in the evaluation of the group refractive index, which is then obtained accurately from two uncalibrated lengths. Measurements of two standard thickness coverslips revealed group indices of 1.5426±0.0042 and 1.5434±0.0046, with accuracies quoted at the 95% confidence level. This agreed with the dispersion data of the coverslip manufacturer and therefore validates our method. Our method provides a sample specific and accurate group refractive index quantification using the same Fourier domain interferometer that is to be calibrated for the length. This reduces significantly the requirements of the calibration transfer standard.

Implication of a Central Cysteine Residue and the HHCC Domain of Moloney Murine Leukemia Virus Integrase Protein in Functional Multimerization

PubMed Central

Donzella, George A.; Leon, Oscar; Roth, Monica J.

1998-01-01

Moloney murine leukemia virus (M-MuLV) IN-IN protein interactions important for catalysis of strand transfer and unimolecular and bimolecular disintegration reactions were investigated by using a panel of chemically modified M-MuLV IN proteins. Functional complementation of an HHCC-deleted protein (NΔ105) by an independent HHCC domain (CΔ232) was severely compromised by NEM modification of either subunit. Productive NΔ105 IN-DNA interactions with a disintegration substrate lacking a long terminal repeat 5′-single-stranded tail also required complementation by a functional HHCC domain. Virus encoding the C209A M-MuLV IN mutation exhibited delayed virion production and replication kinetics. PMID:9445080

Significance of a Recurring Function in Energy Transfer

NASA Astrophysics Data System (ADS)

Mishra, Subodha

2017-05-01

The appearance of a unique function in the energy transfer from one system to the other in different physical situations such as electrical, mechanical, optical, and quantum mechanical processes is established in this work. Though the laws governing the energy transformation and its transfer from system to system are well known, here we notice a unity in diversity; a unique function appears in various cases of energy transfer whether it is a classical or a quantum mechanical process. We consider four examples, well known in elementary physics, from the fields of electricity, mechanics, optics, and quantum mechanics. We find that this unique function is in fact the transfer function corresponding to all these physical situations, and the interesting and intriguing finding is that the inverse Laplace transform of this transfer function, which is the impulse-response function of the systems when multiplied by a factor of -½, is the solution of a linear differential equation for an "instantly forced critically damped harmonic oscillator." It is important to note that though the physical phenomena considered are quite distinct, the underlying process in the language of impulse-response of the system in the time domain is a unique one. To the best of our knowledge we have not seen anywhere the above analysis of determining the unique function or its description as a transfer function in literature.

Improved Displacement Transfer Functions for Structure Deformed Shape Predictions Using Discretely Distributed Surface Strains

NASA Technical Reports Server (NTRS)

Ko, William L.; Fleischer, Van Tran

2012-01-01

In the formulations of earlier Displacement Transfer Functions for structure shape predictions, the surface strain distributions, along a strain-sensing line, were represented with piecewise linear functions. To improve the shape-prediction accuracies, Improved Displacement Transfer Functions were formulated using piecewise nonlinear strain representations. Through discretization of an embedded beam (depth-wise cross section of a structure along a strain-sensing line) into multiple small domains, piecewise nonlinear functions were used to describe the surface strain distributions along the discretized embedded beam. Such piecewise approach enabled the piecewise integrations of the embedded beam curvature equations to yield slope and deflection equations in recursive forms. The resulting Improved Displacement Transfer Functions, written in summation forms, were expressed in terms of beam geometrical parameters and surface strains along the strain-sensing line. By feeding the surface strains into the Improved Displacement Transfer Functions, structural deflections could be calculated at multiple points for mapping out the overall structural deformed shapes for visual display. The shape-prediction accuracies of the Improved Displacement Transfer Functions were then examined in view of finite-element-calculated deflections using different tapered cantilever tubular beams. It was found that by using the piecewise nonlinear strain representations, the shape-prediction accuracies could be greatly improved, especially for highly-tapered cantilever tubular beams.

How Phosphotransferase System-Related Protein Phosphorylation Regulates Carbohydrate Metabolism in Bacteria†

PubMed Central

Deutscher, Josef; Francke, Christof; Postma, Pieter W.

2006-01-01

The phosphoenolpyruvate(PEP):carbohydrate phosphotransferase system (PTS) is found only in bacteria, where it catalyzes the transport and phosphorylation of numerous monosaccharides, disaccharides, amino sugars, polyols, and other sugar derivatives. To carry out its catalytic function in sugar transport and phosphorylation, the PTS uses PEP as an energy source and phosphoryl donor. The phosphoryl group of PEP is usually transferred via four distinct proteins (domains) to the transported sugar bound to the respective membrane component(s) (EIIC and EIID) of the PTS. The organization of the PTS as a four-step phosphoryl transfer system, in which all P derivatives exhibit similar energy (phosphorylation occurs at histidyl or cysteyl residues), is surprising, as a single protein (or domain) coupling energy transfer and sugar phosphorylation would be sufficient for PTS function. A possible explanation for the complexity of the PTS was provided by the discovery that the PTS also carries out numerous regulatory functions. Depending on their phosphorylation state, the four proteins (domains) forming the PTS phosphorylation cascade (EI, HPr, EIIA, and EIIB) can phosphorylate or interact with numerous non-PTS proteins and thereby regulate their activity. In addition, in certain bacteria, one of the PTS components (HPr) is phosphorylated by ATP at a seryl residue, which increases the complexity of PTS-mediated regulation. In this review, we try to summarize the known protein phosphorylation-related regulatory functions of the PTS. As we shall see, the PTS regulation network not only controls carbohydrate uptake and metabolism but also interferes with the utilization of nitrogen and phosphorus and the virulence of certain pathogens. PMID:17158705

On the dependence of the domain of values of functionals of hypersonic aerodynamics on controls

NASA Astrophysics Data System (ADS)

Bilchenko, Grigory; Bilchenko, Nataly

2018-05-01

The properties of mathematical model of control of heat and mass transfer in laminar boundary layer on permeable cylindrical and spherical surfaces of the hypersonic aircraft are considered. Dependences of hypersonic aerodynamics functionals (the total heat flow and the total Newton friction force) on controls (the blowing into boundary layer, the temperature factor, the magnetic field) are investigated. The domains of allowed values of functionals of hypersonic aerodynamics are obtained. The results of the computational experiments are presented: the dependences of total heat flow on controls; the dependences of total Newton friction force on controls; the mutual dependences of functionals (as the domains of allowed values "Heat and Friction"); the dependences of blowing system power on controls. The influences of magnetic field and dissociation on the domain of "Heat and Friction" allowed values are studied. It is proved that for any fixed constant value of magnetic field the blowing system power is a symmetric function of constant dimensionless controls (the blowing into boundary layer and the temperature factor). It is shown that the obtained domain of allowed values of functionals of hypersonic aerodynamics depending on permissible range of controls may be used in engineering.

Loss of a Trans-Splicing nad1 Intron from Geraniaceae and Transfer of the Maturase Gene matR to the Nucleus in Pelargonium

PubMed Central

Grewe, Felix; Zhu, Andan; Mower, Jeffrey P.

2016-01-01

The mitochondrial nad1 gene of seed plants has a complex structure, including four introns in cis or trans configurations and a maturase gene (matR) hosted within the final intron. In the geranium family (Geraniaceae), however, sequencing of representative species revealed that three of the four introns, including one in a trans configuration and another that hosts matR, were lost from the nad1 gene in their common ancestor. Despite the loss of the host intron, matR has been retained as a freestanding gene in most genera of the family, indicating that this maturase has additional functions beyond the splicing of its host intron. In the common ancestor of Pelargonium, matR was transferred to the nuclear genome, where it was split into two unlinked genes that encode either its reverse transcriptase or maturase domain. Both nuclear genes are transcribed and contain predicted mitochondrial targeting signals, suggesting that they express functional proteins that are imported into mitochondria. The nuclear localization and split domain structure of matR in the Pelargonium nuclear genome offers a unique opportunity to assess the function of these two domains using transgenic approaches. PMID:27664178

Expertise facilitates the transfer of anticipation skill across domains.

PubMed

Rosalie, Simon M; Müller, Sean

2014-02-01

It is unclear whether perceptual-motor skill transfer is based upon similarity between the learning and transfer domains per identical elements theory, or facilitated by an understanding of underlying principles in accordance with general principle theory. Here, the predictions of identical elements theory, general principle theory, and aspects of a recently proposed model for the transfer of perceptual-motor skill with respect to expertise in the learning and transfer domains are examined. The capabilities of expert karate athletes, near-expert karate athletes, and novices to anticipate and respond to stimulus skills derived from taekwondo and Australian football were investigated in ecologically valid contexts using an in situ temporal occlusion paradigm and complex whole-body perceptual-motor skills. Results indicated that the karate experts and near-experts are as capable of using visual information to anticipate and guide motor skill responses as domain experts and near-experts in the taekwondo transfer domain, but only karate experts could perform like domain experts in the Australian football transfer domain. Findings suggest that transfer of anticipation skill is based upon expertise and an understanding of principles but may be supplemented by similarities that exist between the stimulus and response elements of the learning and transfer domains.

Crystal Structure of the Human, FIC-Domain Containing Protein HYPE and Implications for Its Functions

PubMed Central

Bunney, Tom D.; Cole, Ambrose R.; Broncel, Malgorzata; Esposito, Diego; Tate, Edward W.; Katan, Matilda

2014-01-01

Summary Protein AMPylation, the transfer of AMP from ATP to protein targets, has been recognized as a new mechanism of host-cell disruption by some bacterial effectors that typically contain a FIC-domain. Eukaryotic genomes also encode one FIC-domain protein, HYPE, which has remained poorly characterized. Here we describe the structure of human HYPE, solved by X-ray crystallography, representing the first structure of a eukaryotic FIC-domain protein. We demonstrate that HYPE forms stable dimers with structurally and functionally integrated FIC-domains and with TPR-motifs exposed for protein-protein interactions. As HYPE also uniquely possesses a transmembrane helix, dimerization is likely to affect its positioning and function in the membrane vicinity. The low rate of autoAMPylation of the wild-type HYPE could be due to autoinhibition, consistent with the mechanism proposed for a number of putative FIC AMPylators. Our findings also provide a basis to further consider possible alternative cofactors of HYPE and distinct modes of target-recognition. PMID:25435325

Crystal structure of the human, FIC-domain containing protein HYPE and implications for its functions.

PubMed

Bunney, Tom D; Cole, Ambrose R; Broncel, Malgorzata; Esposito, Diego; Tate, Edward W; Katan, Matilda

2014-12-02

Protein AMPylation, the transfer of AMP from ATP to protein targets, has been recognized as a new mechanism of host-cell disruption by some bacterial effectors that typically contain a FIC-domain. Eukaryotic genomes also encode one FIC-domain protein,HYPE, which has remained poorly characterized.Here we describe the structure of human HYPE, solved by X-ray crystallography, representing the first structure of a eukaryotic FIC-domain protein. We demonstrate that HYPE forms stable dimers with structurally and functionally integrated FIC-domains and with TPR-motifs exposed for protein-protein interactions. As HYPE also uniquely possesses a transmembrane helix, dimerization is likely to affect its positioning and function in the membrane vicinity. The low rate of auto AMPylation of the wild-type HYPE could be due to autoinhibition, consistent with the mechanism proposed for a number of putative FIC AMPylators. Our findings also provide a basis to further consider possible alternative cofactors of HYPE and distinct modes of target-recognition.

Domain Evolution and Functional Diversification of Sulfite Reductases

NASA Astrophysics Data System (ADS)

Dhillon, Ashita; Goswami, Sulip; Riley, Monica; Teske, Andreas; Sogin, Mitchell

2005-02-01

Sulfite reductases are key enzymes of assimilatory and dissimilatory sulfur metabolism, which occur in diverse bacterial and archaeal lineages. They share a highly conserved domain "C-X5-C-n-C-X3-C" for binding siroheme and iron-sulfur clusters that facilitate electron transfer to the substrate. For each sulfite reductase cluster, the siroheme-binding domain is positioned slightly differently at the N-terminus of dsrA and dsrB, while in the assimilatory proteins the siroheme domain is located at the C-terminus. Our sequence and phylogenetic analysis of the siroheme-binding domain shows that sulfite reductase sequences diverged from a common ancestor into four separate clusters (aSir, alSir, dsr, and asrC) that are biochemically distinct; each serves a different assimilatory or dissimilatory role in sulfur metabolism. The phylogenetic distribution and functional grouping in sulfite reductase clusters (dsrA and dsrB vs. aSiR, asrC, and alSir) suggest that their functional diversification during evolution may have preceded the bacterial/archaeal divergence.

A hybrid two-component system protein from Azospirillum brasilense Sp7 was involved in chemotaxis.

PubMed

Cui, Yanhua; Tu, Ran; Wu, Lixian; Hong, Yuanyuan; Chen, Sanfeng

2011-09-20

We here report the sequence and functional analysis of org35 of Azospirillum brasilense Sp7, which was originally identified to be able to interact with NifA in yeast-two-hybrid system. The org35 encodes a hybrid two-component system protein, including N-terminal PAS domains, a histidine kinase (HPK) domain and a response regulator (RR) domain in C-terminal. To determine the function of the Org35, a deletion-insertion mutant in PAS domain [named Sp7353] and a complemental strain Sp7353C were constructed. The mutant had reduced chemotaxis ability compared to that of wild-type, and the complemental strain was similar to the wild-type strain. These data suggested that the A. brasilense org35 played a key role in chemotaxis. Variants containing different domains of the org35 were expressed, and the functions of these domains were studied in vitro. Phosphorylation assays in vitro demonstrated that the HPK domain of Org35 possessed the autokinase activity and that the phosphorylated HPK was able to transfer phosphate groups to the RR domain. The result indicated Org35 was a phosphorylation-communicating protein. Copyright © 2010 Elsevier GmbH. All rights reserved.

Human operator identification model and related computer programs

NASA Technical Reports Server (NTRS)

Kessler, K. M.; Mohr, J. N.

1978-01-01

Four computer programs which provide computational assistance in the analysis of man/machine systems are reported. The programs are: (1) Modified Transfer Function Program (TF); (2) Time Varying Response Program (TVSR); (3) Optimal Simulation Program (TVOPT); and (4) Linear Identification Program (SCIDNT). The TV program converts the time domain state variable system representative to frequency domain transfer function system representation. The TVSR program computes time histories of the input/output responses of the human operator model. The TVOPT program is an optimal simulation program and is similar to TVSR in that it produces time histories of system states associated with an operator in the loop system. The differences between the two programs are presented. The SCIDNT program is an open loop identification code which operates on the simulated data from TVOPT (or TVSR) or real operator data from motion simulators.

Modeling of Atmospheric Turbulence as Disturbances for Control Design and Evaluation of High Speed Propulsion Systems

NASA Technical Reports Server (NTRS)

Kopasakis, George

2010-01-01

Atmospheric turbulence models are necessary for the design of both inlet/engine and flight controls, as well as for studying integrated couplings between the propulsion and the vehicle structural dynamics for supersonic vehicles. Models based on the Kolmogorov spectrum have been previously utilized to model atmospheric turbulence. In this paper, a more accurate model is developed in its representative fractional order form, typical of atmospheric disturbances. This is accomplished by first scaling the Kolmogorov spectral to convert them into finite energy von Karman forms. Then a generalized formulation is developed in frequency domain for these scale models that approximates the fractional order with the products of first order transfer functions. Given the parameters describing the conditions of atmospheric disturbances and utilizing the derived formulations, the objective is to directly compute the transfer functions that describe these disturbances for acoustic velocity, temperature, pressure and density. Utilizing these computed transfer functions and choosing the disturbance frequencies of interest, time domain simulations of these representative atmospheric turbulences can be developed. These disturbance representations are then used to first develop considerations for disturbance rejection specifications for the design of the propulsion control system, and then to evaluate the closed-loop performance.

Molecular insights into RBR E3 ligase ubiquitin transfer mechanisms.

PubMed

Dove, Katja K; Stieglitz, Benjamin; Duncan, Emily D; Rittinger, Katrin; Klevit, Rachel E

2016-08-01

RING-in-between-RING (RBR) ubiquitin (Ub) ligases are a distinct class of E3s, defined by a RING1 domain that binds E2 Ub-conjugating enzyme and a RING2 domain that contains an active site cysteine similar to HECT-type E3s. Proposed to function as RING/HECT hybrids, details regarding the Ub transfer mechanism used by RBRs have yet to be defined. When paired with RING-type E3s, E2s perform the final step of Ub ligation to a substrate. In contrast, when paired with RBR E3s, E2s must transfer Ub onto the E3 to generate a E3~Ub intermediate. We show that RBRs utilize two strategies to ensure transfer of Ub from the E2 onto the E3 active site. First, RING1 domains of HHARI and RNF144 promote open E2~Ubs. Second, we identify a Ub-binding site on HHARI RING2 important for its recruitment to RING1-bound E2~Ub. Mutations that ablate Ub binding to HHARI RING2 also decrease RBR ligase activity, consistent with RING2 recruitment being a critical step for the RBR Ub transfer mechanism. Finally, we demonstrate that the mechanism defined here is utilized by a variety of RBRs. © 2016 The Authors.

A molecular dynamics simulation study of amino acid selectivity of LeuRS editing domain from Thermus thermophilus.

PubMed

Rayevsky, Alexey; Sharifi, Mohsen; Tukalo, Michael

2018-06-18

The accuracy of protein synthesis is provided by the editing functions of aminoacyl-tRNA synthetases (aaRSs), a mechanism that eliminates misactivated amino acids or mischarged tRNAs. Despite research efforts, some molecular bases of these mechanisms are still unclear. The post-transfer editing pathway of leucyl-tRNA synthetase (LeuRS) carried out in a special insertion domain (the Connective Polypeptide 1 or CP1), as editing domain. Recently, it was shown by in vivo studies and was supported by mutagenesis, and the kinetics approaches that the CP1 domain of LeuRS has discriminatory power for different substrates. The goal of this work is to investigate the structural basis for amino acid recognition of LeuRS post-transfer editing processes with molecular dynamics (MD) simulation method. To pursue this aim, the molecular modeling studies on Thermus thermophiles LeuRS (LeuRSTT) with two post-transfer substrates (norvalyl-tRNA Leu and isoleucyl-tRNA Leu ) was performed. Our results revealed that post-transfer substrate norvalyl-tRNA Leu is more favorable. Moreover, the MD simulations show that branched side chain of Ile-A76 cannot allow water molecules to get close, which leads to a significant decrease in the rate of hydrolysis. Finally, the study showed that site mutation Asp347Ala has elucidated a number of fine structural differences in the binding mode of two post-transfer substrates to the active centre of LeuRS editing domain and two conserved threonines, namely Thr247 and Thr248, are responsible for the amino acid selection through the interaction with substrates. Copyright © 2018 Elsevier Inc. All rights reserved.

A bipartite signal mediates the transfer of type IV secretion substrates of Bartonella henselae into human cells.

PubMed

Schulein, Ralf; Guye, Patrick; Rhomberg, Thomas A; Schmid, Michael C; Schröder, Gunnar; Vergunst, Annette C; Carena, Ilaria; Dehio, Christoph

2005-01-18

Bacterial type IV secretion (T4S) systems mediate the transfer of macromolecular substrates into various target cells, e.g., the conjugative transfer of DNA into bacteria or the transfer of virulence proteins into eukaryotic host cells. The T4S apparatus VirB of the vascular tumor-inducing pathogen Bartonella henselae causes subversion of human endothelial cell (HEC) function. Here we report the identification of multiple protein substrates of VirB, which, upon translocation into HEC, mediate all known VirB-dependent cellular changes. These Bartonella-translocated effector proteins (Beps) A-G are encoded together with the VirB system and the T4S coupling protein VirD4 on a Bartonella-specific pathogenicity island. The Beps display a modular architecture, suggesting an evolution by extensive domain duplication and reshuffling. The C terminus of each Bep harbors at least one copy of the Bep-intracellular delivery domain and a short positively charged tail sequence. This biparte C terminus constitutes a transfer signal that is sufficient to mediate VirB/VirD4-dependent intracellular delivery of reporter protein fusions. The Bep-intracellular delivery domain is also present in conjugative relaxases of bacterial conjugation systems. We exemplarily show that the C terminus of such a conjugative relaxase mediates protein transfer through the Bartonella henselae VirB/VirD4 system into HEC. Conjugative relaxases may thus represent the evolutionary origin of the here defined T4S signal for protein transfer into human cells.

Domain adaptation via transfer component analysis.

PubMed

Pan, Sinno Jialin; Tsang, Ivor W; Kwok, James T; Yang, Qiang

2011-02-01

Domain adaptation allows knowledge from a source domain to be transferred to a different but related target domain. Intuitively, discovering a good feature representation across domains is crucial. In this paper, we first propose to find such a representation through a new learning method, transfer component analysis (TCA), for domain adaptation. TCA tries to learn some transfer components across domains in a reproducing kernel Hilbert space using maximum mean miscrepancy. In the subspace spanned by these transfer components, data properties are preserved and data distributions in different domains are close to each other. As a result, with the new representations in this subspace, we can apply standard machine learning methods to train classifiers or regression models in the source domain for use in the target domain. Furthermore, in order to uncover the knowledge hidden in the relations between the data labels from the source and target domains, we extend TCA in a semisupervised learning setting, which encodes label information into transfer components learning. We call this extension semisupervised TCA. The main contribution of our work is that we propose a novel dimensionality reduction framework for reducing the distance between domains in a latent space for domain adaptation. We propose both unsupervised and semisupervised feature extraction approaches, which can dramatically reduce the distance between domain distributions by projecting data onto the learned transfer components. Finally, our approach can handle large datasets and naturally lead to out-of-sample generalization. The effectiveness and efficiency of our approach are verified by experiments on five toy datasets and two real-world applications: cross-domain indoor WiFi localization and cross-domain text classification.

Using complementary approaches to identify trans-domain nuclear gene transfers in the extremophile Galdieria sulphuraria (Rhodophyta).

PubMed

Pandey, Ravi S; Saxena, Garima; Bhattacharya, Debashish; Qiu, Huan; Azad, Rajeev K

2017-02-01

Identification of horizontal gene transfers (HGTs) has primarily relied on phylogenetic tree based methods, which require a rich sampling of sequenced genomes to ensure a reliable inference. Because the success of phylogenetic approaches depends on the breadth and depth of the database, researchers usually apply stringent filters to detect only the most likely gene transfers in the genomes of interest. One such study focused on a highly conservative estimate of trans-domain gene transfers in the extremophile eukaryote, Galdieria sulphuraria (Galdieri) Merola (Rhodophyta), by applying multiple filters in their phylogenetic pipeline. This led to the identification of 75 inter-domain acquisitions from Bacteria or Archaea. Because of the evolutionary, ecological, and potential biotechnological significance of foreign genes in algae, alternative approaches and pipelines complementing phylogenetics are needed for a more comprehensive assessment of HGT. We present here a novel pipeline that uncovered 17 novel foreign genes of prokaryotic origin in G. sulphuraria, results that are supported by multiple lines of evidence including composition-based, comparative data, and phylogenetics. These genes encode a variety of potentially adaptive functions, from metabolite transport to DNA repair. © 2016 Phycological Society of America.

A robust methodology to subclassify pseudokinases based on their nucleotide-binding properties

PubMed Central

Murphy, James M.; Zhang, Qingwei; Young, Samuel N.; Reese, Michael L.; Bailey, Fiona P.; Eyers, Patrick A.; Ungureanu, Daniela; Hammaren, Henrik; Silvennoinen, Olli; Varghese, Leila N.; Chen, Kelan; Tripaydonis, Anne; Jura, Natalia; Fukuda, Koichi; Qin, Jun; Nimchuk, Zachary; Mudgett, Mary Beth; Elowe, Sabine; Gee, Christine L.; Liu, Ling; Daly, Roger J.; Manning, Gerard; Babon, Jeffrey J.; Lucet, Isabelle S.

2017-01-01

Protein kinase-like domains that lack conserved residues known to catalyse phosphoryl transfer, termed pseudokinases, have emerged as important signalling domains across all kingdoms of life. Although predicted to function principally as catalysis-independent protein-interaction modules, several pseudokinase domains have been attributed unexpected catalytic functions, often amid controversy. We established a thermal-shift assay as a benchmark technique to define the nucleotide-binding properties of kinase-like domains. Unlike in vitro kinase assays, this assay is insensitive to the presence of minor quantities of contaminating kinases that may otherwise lead to incorrect attribution of catalytic functions to pseudokinases. We demonstrated the utility of this method by classifying 31 diverse pseudokinase domains into four groups: devoid of detectable nucleotide or cation binding; cation-independent nucleotide binding; cation binding; and nucleotide binding enhanced by cations. Whereas nine pseudokinases bound ATP in a divalent cation-dependent manner, over half of those examined did not detectably bind nucleotides, illustrating that pseudokinase domains predominantly function as non-catalytic protein-interaction modules within signalling networks and that only a small subset is potentially catalytically active. We propose that henceforth the thermal-shift assay be adopted as the standard technique for establishing the nucleotide-binding and catalytic potential of kinase-like domains. PMID:24107129

Numerical method based on transfer function for eliminating water vapor noise from terahertz spectra.

PubMed

Huang, Y; Sun, P; Zhang, Z; Jin, C

2017-07-10

Water vapor noise in the air affects the accuracy of optical parameters extracted from terahertz (THz) time-domain spectroscopy. In this paper, a numerical method was proposed to eliminate water vapor noise from the THz spectra. According to the Van Vleck-Weisskopf function and the linear absorption spectrum of water molecules in the HITRAN database, we simulated the water vapor absorption spectrum and real refractive index spectrum with a particular line width. The continuum effect of water vapor molecules was also considered. Theoretical transfer function of a different humidity was constructed through the theoretical calculation of the water vapor absorption coefficient and the real refractive index. The THz signal of the Lacidipine sample containing water vapor background noise in the continuous frequency domain of 0.5-1.8 THz was denoised by use of the method. The results show that the optical parameters extracted from the denoised signal are closer to the optical parameters in the dry nitrogen environment.

Single TRAM domain RNA-binding proteins in Archaea: functional insight from Ctr3 from the Antarctic methanogen Methanococcoides burtonii.

PubMed

Taha; Siddiqui, K S; Campanaro, S; Najnin, T; Deshpande, N; Williams, T J; Aldrich-Wright, J; Wilkins, M; Curmi, P M G; Cavicchioli, R

2016-09-01

TRAM domain proteins present in Archaea and Bacteria have a β-barrel shape with anti-parallel β-sheets that form a nucleic acid binding surface; a structure also present in cold shock proteins (Csps). Aside from protein structures, experimental data defining the function of TRAM domains is lacking. Here, we explore the possible functional properties of a single TRAM domain protein, Ctr3 (cold-responsive TRAM domain protein 3) from the Antarctic archaeon Methanococcoides burtonii that has increased abundance during low temperature growth. Ribonucleic acid (RNA) bound by Ctr3 in vitro was determined using RNA-seq. Ctr3-bound M. burtonii RNA with a preference for transfer (t)RNA and 5S ribosomal RNA, and a potential binding motif was identified. In tRNA, the motif represented the C loop; a region that is conserved in tRNA from all domains of life and appears to be solvent exposed, potentially providing access for Ctr3 to bind. Ctr3 and Csps are structurally similar and are both inferred to function in low temperature translation. The broad representation of single TRAM domain proteins within Archaea compared with their apparent absence in Bacteria, and scarcity of Csps in Archaea but prevalence in Bacteria, suggests they represent distinct evolutionary lineages of functionally equivalent RNA-binding proteins. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Nanoantioxidant-driven plasmon enhanced proton-coupled electron transfer

NASA Astrophysics Data System (ADS)

Sotiriou, Georgios A.; Blattmann, Christoph O.; Deligiannakis, Yiannis

2015-12-01

Proton-coupled electron transfer (PCET) reactions involve the transfer of a proton and an electron and play an important role in a number of chemical and biological processes. Here, we describe a novel phenomenon, plasmon-enhanced PCET, which is manifested using SiO2-coated Ag nanoparticles functionalized with gallic acid (GA), a natural antioxidant molecule that can perform PCET. These GA-functionalized nanoparticles show enhanced plasmonic response at near-IR wavelengths, due to particle agglomeration caused by the GA molecules. Near-IR laser irradiation induces strong local hot-spots on the SiO2-coated Ag nanoparticles, as evidenced by surface enhanced Raman scattering (SERS). This leads to plasmon energy transfer to the grafted GA molecules that lowers the GA-OH bond dissociation enthalpy by at least 2 kcal mol-1 and therefore facilitates PCET. The nanoparticle-driven plasmon-enhancement of PCET brings together the so far unrelated research domains of nanoplasmonics and electron/proton translocation with significant impact on applications based on interfacial electron/proton transfer.Proton-coupled electron transfer (PCET) reactions involve the transfer of a proton and an electron and play an important role in a number of chemical and biological processes. Here, we describe a novel phenomenon, plasmon-enhanced PCET, which is manifested using SiO2-coated Ag nanoparticles functionalized with gallic acid (GA), a natural antioxidant molecule that can perform PCET. These GA-functionalized nanoparticles show enhanced plasmonic response at near-IR wavelengths, due to particle agglomeration caused by the GA molecules. Near-IR laser irradiation induces strong local hot-spots on the SiO2-coated Ag nanoparticles, as evidenced by surface enhanced Raman scattering (SERS). This leads to plasmon energy transfer to the grafted GA molecules that lowers the GA-OH bond dissociation enthalpy by at least 2 kcal mol-1 and therefore facilitates PCET. The nanoparticle-driven plasmon-enhancement of PCET brings together the so far unrelated research domains of nanoplasmonics and electron/proton translocation with significant impact on applications based on interfacial electron/proton transfer. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04942c

Multi-Domain Transfer Learning for Early Diagnosis of Alzheimer's Disease.

PubMed

Cheng, Bo; Liu, Mingxia; Shen, Dinggang; Li, Zuoyong; Zhang, Daoqiang

2017-04-01

Recently, transfer learning has been successfully applied in early diagnosis of Alzheimer's Disease (AD) based on multi-domain data. However, most of existing methods only use data from a single auxiliary domain, and thus cannot utilize the intrinsic useful correlation information from multiple domains. Accordingly, in this paper, we consider the joint learning of tasks in multi-auxiliary domains and the target domain, and propose a novel Multi-Domain Transfer Learning (MDTL) framework for early diagnosis of AD. Specifically, the proposed MDTL framework consists of two key components: 1) a multi-domain transfer feature selection (MDTFS) model that selects the most informative feature subset from multi-domain data, and 2) a multi-domain transfer classification (MDTC) model that can identify disease status for early AD detection. We evaluate our method on 807 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database using baseline magnetic resonance imaging (MRI) data. The experimental results show that the proposed MDTL method can effectively utilize multi-auxiliary domain data for improving the learning performance in the target domain, compared with several state-of-the-art methods.

Dimensional feature weighting utilizing multiple kernel learning for single-channel talker location discrimination using the acoustic transfer function.

PubMed

Takashima, Ryoichi; Takiguchi, Tetsuya; Ariki, Yasuo

2013-02-01

This paper presents a method for discriminating the location of the sound source (talker) using only a single microphone. In a previous work, the single-channel approach for discriminating the location of the sound source was discussed, where the acoustic transfer function from a user's position is estimated by using a hidden Markov model of clean speech in the cepstral domain. In this paper, each cepstral dimension of the acoustic transfer function is newly weighted, in order to obtain the cepstral dimensions having information that is useful for classifying the user's position. Then, this paper proposes a feature-weighting method for the cepstral parameter using multiple kernel learning, defining the base kernels for each cepstral dimension of the acoustic transfer function. The user's position is trained and classified by support vector machine. The effectiveness of this method has been confirmed by sound source (talker) localization experiments performed in different room environments.

Incomplete Multisource Transfer Learning.

PubMed

Ding, Zhengming; Shao, Ming; Fu, Yun

2018-02-01

Transfer learning is generally exploited to adapt well-established source knowledge for learning tasks in weakly labeled or unlabeled target domain. Nowadays, it is common to see multiple sources available for knowledge transfer, each of which, however, may not include complete classes information of the target domain. Naively merging multiple sources together would lead to inferior results due to the large divergence among multiple sources. In this paper, we attempt to utilize incomplete multiple sources for effective knowledge transfer to facilitate the learning task in target domain. To this end, we propose an incomplete multisource transfer learning through two directional knowledge transfer, i.e., cross-domain transfer from each source to target, and cross-source transfer. In particular, in cross-domain direction, we deploy latent low-rank transfer learning guided by iterative structure learning to transfer knowledge from each single source to target domain. This practice reinforces to compensate for any missing data in each source by the complete target data. While in cross-source direction, unsupervised manifold regularizer and effective multisource alignment are explored to jointly compensate for missing data from one portion of source to another. In this way, both marginal and conditional distribution discrepancy in two directions would be mitigated. Experimental results on standard cross-domain benchmarks and synthetic data sets demonstrate the effectiveness of our proposed model in knowledge transfer from incomplete multiple sources.

Interdomain electron transfer in cellobiose dehydrogenase is governed by surface electrostatics.

PubMed

Kadek, Alan; Kavan, Daniel; Marcoux, Julien; Stojko, Johann; Felice, Alfons K G; Cianférani, Sarah; Ludwig, Roland; Halada, Petr; Man, Petr

2017-02-01

Cellobiose dehydrogenase (CDH) is a fungal extracellular oxidoreductase which fuels lytic polysaccharide monooxygenase with electrons during cellulose degradation. Interdomain electron transfer between the flavin and cytochrome domain in CDH, preceding the electron flow to lytic polysaccharide monooxygenase, is known to be pH dependent, but the exact mechanism of this regulation has not been experimentally proven so far. To investigate the structural aspects underlying the domain interaction in CDH, hydrogen/deuterium exchange (HDX-MS) with improved proteolytic setup (combination of nepenthesin-1 with rhizopuspepsin), native mass spectrometry with ion mobility and electrostatics calculations were used. HDX-MS revealed pH-dependent changes in solvent accessibility and hydrogen bonding at the interdomain interface. Electrostatics calculations identified these differences to result from charge neutralization by protonation and together with ion mobility pointed at higher electrostatic repulsion between CDH domains at neutral pH. In addition, we uncovered extensive O-glycosylation in the linker region and identified the long-unknown exact cleavage point in papain-mediated domain separation. Transition of CDH between its inactive (open) and interdomain electron transfer-capable (closed) state is shown to be governed by changes in the protein surface electrostatics at the domain interface. Our study confirms that the interdomain electrostatic repulsion is the key factor modulating the functioning of CDH. The results presented in this paper provide experimental evidence for the role of charge repulsion in the interdomain electron transfer in cellobiose dehydrogenases, which is relevant for exploiting their biotechnological potential in biosensors and biofuel cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Hemoglobin binding and catalytic heme extraction by IsdB near iron transporter domains.

PubMed

Bowden, Catherine F M; Verstraete, Meghan M; Eltis, Lindsay D; Murphy, Michael E P

2014-04-15

The Isd (iron-regulated surface determinant) system is a multiprotein transporter that allows bacterium Staphylococcus aureus to take up iron from hemoglobin (Hb) during human infection. In this system, IsdB is a cell wall-anchored surface protein that contains two near iron transporter (NEAT) domains, one of which binds heme. IsdB rapidly extracts heme from Hb and transfers it to IsdA for relay into the bacterial cell. Using a series of recombinant IsdB constructs that included at least one NEAT domain, we demonstrated that both domains are required to bind Hb with high affinity (KD = 0.42 ± 0.05 μM) and to extract heme from Hb. Moreover, IsdB extracted heme only from oxidized metHb, although it also bound oxyHb and the Hb-CO complex. In a reconstituted model of the biological heme relay pathway, IsdB catalyzed the transfer of heme from metHb to IsdA with a Km for metHb of 0.75 ± 0.07 μN and a kcat of 0.22 ± 0.01 s(-1). The latter is consistent with the transfer of heme from metHb to IsdB being the rate-limiting step. With both NEAT domains and the linker region present in a single contiguous polypeptide, high-affinity Hb binding was achieved, rapid heme uptake was observed, and multiple turnovers of heme extraction from metHb and transfer to IsdA were conducted, representing all known Hb-heme uptake functions of the full-length IsdB protein.

Effect of pole zero location on system dynamics of boost converter for micro grid

NASA Astrophysics Data System (ADS)

Lavanya, A.; Vijayakumar, K.; Navamani, J. D.; Jayaseelan, N.

2018-04-01

Green clean energy like photo voltaic, wind energy, fuel cell can be brought together by microgrid.For low voltage sources like photovoltaic cell boost converter is very much essential. This paper explores the dynamic analysis of boost converter in a continuous conduction mode (CCM). The transient performance and stability analysis is carried out in this paper using time domain analysis and frequency domain analysis techniques. Boost converter is simulated using both PSIM and MATLAB software. Furthermore, state space model obtained and the transfer function is derived. The converter behaviour when a step input is applied is analyzed and stability of the converter is analyzed from bode plot frequency for open loop. Effect of the locations of poles and zeros in the transfer function of boost converter and how the performance parameters are affected is discussed in this paper. Closed loop performance with PI controller is also analyzed for boost converter.

Multi-Domain Transfer Learning for Early Diagnosis of Alzheimer’s Disease

PubMed Central

Cheng, Bo; Liu, Mingxia; Li, Zuoyong

2017-01-01

Recently, transfer learning has been successfully applied in early diagnosis of Alzheimer’s Disease (AD) based on multi-domain data. However, most of existing methods only use data from a single auxiliary domain, and thus cannot utilize the intrinsic useful correlation information from multiple domains. Accordingly, in this paper, we consider the joint learning of tasks in multi-auxiliary domains and the target domain, and propose a novel Multi-Domain Transfer Learning (MDTL) framework for early diagnosis of AD. Specifically, the proposed MDTL framework consists of two key components: 1) a multi-domain transfer feature selection (MDTFS) model that selects the most informative feature subset from multi-domain data, and 2) a multidomain transfer classification (MDTC) model that can identify disease status for early AD detection. We evaluate our method on 807 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database using baseline magnetic resonance imaging (MRI) data. The experimental results show that the proposed MDTL method can effectively utilize multi-auxiliary domain data for improving the learning performance in the target domain, compared with several state-of-the-art methods. PMID:27928657

Predicting vertically-nonsequential wetting patterns with a source-responsive model

USGS Publications Warehouse

Nimmo, John R.; Mitchell, Lara

2013-01-01

Water infiltrating into soil of natural structure often causes wetting patterns that do not develop in an orderly sequence. Because traditional unsaturated flow models represent a water advance that proceeds sequentially, they fail to predict irregular development of water distribution. In the source-responsive model, a diffuse domain (D) represents flow within soil matrix material following traditional formulations, and a source-responsive domain (S), characterized in terms of the capacity for preferential flow and its degree of activation, represents preferential flow as it responds to changing water-source conditions. In this paper we assume water undergoing rapid source-responsive transport at any particular time is of negligibly small volume; it becomes sensible at the time and depth where domain transfer occurs. A first-order transfer term represents abstraction from the S to the D domain which renders the water sensible. In tests with lab and field data, for some cases the model shows good quantitative agreement, and in all cases it captures the characteristic patterns of wetting that proceed nonsequentially in the vertical direction. In these tests we determined the values of the essential characterizing functions by inverse modeling. These functions relate directly to observable soil characteristics, rendering them amenable to evaluation and improvement through hydropedologic development.

Transfer and maintenance effects of online working-memory training in normal ageing and mild cognitive impairment.

PubMed

Vermeij, Anouk; Claassen, Jurgen A H R; Dautzenberg, Paul L J; Kessels, Roy P C

2016-10-01

Working memory (WM) is one of the cognitive functions that is susceptible to ageing-related decline. Interventions that are able to improve WM functioning at older age are thus highly relevant. In this pilot study, we explored the transfer effects of core WM training on the WM domain and other cognitive domains in 23 healthy older adults and 18 patients with amnestic mild cognitive impairment (MCI). Performance on neuropsychological tests was assessed before and after completion of the online five-week adaptive WM training, and after a three-month follow-up period. After training, both groups improved on the Digit Span and Spatial Span, gains that were maintained at follow-up. At an individual level, a limited number of participants showed reliable training gain. Healthy older adults, and to a lesser extent MCI patients, additionally improved on figural fluency at group level, but not at individual level. Results furthermore showed that global brain atrophy and hippocampal atrophy, as assessed by MRI, may negatively affect training outcome. Our study examined core WM training, showing gains on trained and untrained tasks within the WM domain, but no broad generalisation to other cognitive domains. More research is needed to evaluate the clinical relevance of these findings and to identify participant characteristics that are predictive of training gain.

Geometrical control of pure spin current induced domain wall depinning.

PubMed

Pfeiffer, A; Reeve, R M; Voto, M; Savero-Torres, W; Richter, N; Vila, L; Attané, J P; Lopez-Diaz, L; Kläui, Mathias

2017-03-01

We investigate the pure spin-current assisted depinning of magnetic domain walls in half ring based Py/Al lateral spin valve structures. Our optimized geometry incorporating a patterned notch in the detector electrode, directly below the Al spin conduit, provides a tailored pinning potential for a transverse domain wall and allows for a precise control over the magnetization configuration and as a result the domain wall pinning. Due to the patterned notch, we are able to study the depinning field as a function of the applied external field for certain applied current densities and observe a clear asymmetry for the two opposite field directions. Micromagnetic simulations show that this can be explained by the asymmetry of the pinning potential. By direct comparison of the calculated efficiencies for different external field and spin current directions, we are able to disentangle the different contributions from the spin transfer torque, Joule heating and the Oersted field. The observed high efficiency of the pure spin current induced spin transfer torque allows for a complete depinning of the domain wall at zero external field for a charge current density of [Formula: see text] A m -2 , which is attributed to the optimal control of the position of the domain wall.

Computerized Adaptive Tests Detect Change Following Orthopaedic Surgery in Youth with Cerebral Palsy.

PubMed

Mulcahey, M J; Slavin, Mary D; Ni, Pengsheng; Vogel, Lawrence C; Kozin, Scott H; Haley, Stephen M; Jette, Alan M

2015-09-16

The Cerebral Palsy Computerized Adaptive Test (CP-CAT) is a parent-reported outcomes instrument for measuring lower and upper-extremity function, activity, and global health across impairment levels and a broad age range of children with cerebral palsy (CP). This study was performed to examine whether the Lower Extremity/Mobility (LE) CP-CAT detects change in mobility following orthopaedic surgery in children with CP. This multicenter, longitudinal study involved administration of the LE CP-CAT, the Pediatric Outcomes Data Collection Instrument (PODCI) Transfer/Mobility and Sports/Physical Functioning domains, and the Timed "Up & Go" test (TUG) before and after elective orthopaedic surgery in a convenience sample of 255 children, four to twenty years of age, who had CP and a Gross Motor Function Classification System (GMFCS) level of I, II, or III. Standardized response means (SRMs) and 95% confidence intervals (CIs) were calculated for all measures at six, twelve, and twenty-four months following surgery. SRM estimates for the LE CP-CAT were significantly greater than the SRM estimates for the PODCI Transfer/Mobility domain at twelve months, the PODCI Sports/Physical Functioning domain at twelve months, and the TUG at twelve and twenty-four months. When the results for the children at GMFCS levels I, II, and III were grouped together, the improvements in function detected by the LE CP-CAT at twelve and twenty-four months were found to be greater than the changes detected by the PODCI Transfer/Mobility and Sports/Physical Functioning scales. The LE CP-CAT outperformed the PODCI scales for GMFCS levels I and III at both of these follow-up intervals; none of the scales performed well for patients with GMFCS level II. The results of this study showed that the LE CP-CAT displayed superior sensitivity to change than the PODCI and TUG scales after musculoskeletal surgery in children with CP. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Application of the sequential quadratic programming algorithm for reconstructing the distribution of optical parameters based on the time-domain radiative transfer equation.

PubMed

Qi, Hong; Qiao, Yao-Bin; Ren, Ya-Tao; Shi, Jing-Wen; Zhang, Ze-Yu; Ruan, Li-Ming

2016-10-17

Sequential quadratic programming (SQP) is used as an optimization algorithm to reconstruct the optical parameters based on the time-domain radiative transfer equation (TD-RTE). Numerous time-resolved measurement signals are obtained using the TD-RTE as forward model. For a high computational efficiency, the gradient of objective function is calculated using an adjoint equation technique. SQP algorithm is employed to solve the inverse problem and the regularization term based on the generalized Gaussian Markov random field (GGMRF) model is used to overcome the ill-posed problem. Simulated results show that the proposed reconstruction scheme performs efficiently and accurately.

Gene transfer, expression, and sarcomeric incorporation of a headless myosin molecule in cardiac myocytes: evidence for a reserve in myofilament motor function

PubMed Central

Vandenboom, Rene; Herron, Todd; Favre, Elizabeth; Albayya, Faris P.

2011-01-01

The purpose of this study was to implement a living myocyte in vitro model system to test whether a motor domain-deleted headless myosin construct could be incorporated into the sarcomere and affect contractility. To this end we used gene transfer to express a “headless” myosin heavy chain (headless-MHC) in complement with the native full-length myosin motors in the cardiac sarcomere. An NH2-terminal Flag epitope was used for unique detection of the motor domain-deleted headless-MHC. Total MHC content (i.e., headless-MHC + endogenous MHC) remained constant, while expression of the headless-MHC in transduced myocytes increased from 24 to 72 h after gene transfer until values leveled off at 96 h after gene transfer, at which time the headless-MHC comprised ∼20% of total MHC. Moreover, immunofluorescence labeling and confocal imaging confirmed expression and demonstrated incorporation of the headless-MHC in the A band of the cardiac sarcomere. Functional measurements in intact myocytes showed that headless-MHC modestly reduced amplitude of dynamic twitch contractions compared with controls (P < 0.05). In chemically permeabilized myocytes, maximum steady-state isometric force and the tension-pCa relationship were unaltered by the headless-MHC. These data suggest that headless-MHC can express to 20% of total myosin and incorporate into the sarcomere yet have modest to no effects on dynamic and steady-state contractile function. This would indicate a degree of functional tolerance in the sarcomere for nonfunctional myosin molecules. PMID:21112946

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.

Adoptive transfer of murine T cells expressing a chimeric-PD1-Dap10 receptor as an immunotherapy for lymphoma.

PubMed

Lynch, Adam; Hawk, William; Nylen, Emily; Ober, Sean; Autin, Pierre; Barber, Amorette

2017-11-01

Adoptive transfer of T cells is a promising cancer therapy and expression of chimeric antigen receptors can enhance tumour recognition and T-cell effector functions. The programmed death protein 1 (PD1) receptor is a prospective target for a chimeric antigen receptor because PD1 ligands are expressed on many cancer types, including lymphoma. Therefore, we developed a murine chimeric PD1 receptor (chPD1) consisting of the PD1 extracellular domain fused to the cytoplasmic domain of CD3ζ. Additionally, chimeric antigen receptor therapies use various co-stimulatory domains to enhance efficacy. Hence, the inclusion of a Dap10 or CD28 co-stimulatory domain in the chPD1 receptor was compared to determine which domain induced optimal anti-tumour immunity in a mouse model of lymphoma. The chPD1 T cells secreted pro-inflammatory cytokines and lysed RMA lymphoma cells. Adoptive transfer of chPD1 T cells significantly reduced established tumours and led to tumour-free survival in lymphoma-bearing mice. When comparing chPD1 receptors containing a Dap10 or CD28 domain, both receptors induced secretion of pro-inflammatory cytokines; however, chPD1-CD28 T cells also secreted anti-inflammatory cytokines whereas chPD1-Dap10 T cells did not. Additionally, chPD1-Dap10 induced a central memory T-cell phenotype compared with chPD1-CD28, which induced an effector memory phenotype. The chPD1-Dap10 T cells also had enhanced in vivo persistence and anti-tumour efficacy compared with chPD1-CD28 T cells. Therefore, adoptive transfer of chPD1 T cells could be a novel therapy for lymphoma and inclusion of the Dap10 co-stimulatory domain in chimeric antigen receptors may induce a preferential cytokine profile and T-cell differentiation phenotype for anti-tumour therapies. © 2017 John Wiley & Sons Ltd.

A bipartite signal mediates the transfer of type IV secretion substrates of Bartonella henselae into human cells

PubMed Central

Schulein, Ralf; Guye, Patrick; Rhomberg, Thomas A.; Schmid, Michael C.; Schröder, Gunnar; Vergunst, Annette C.; Carena, Ilaria; Dehio, Christoph

2005-01-01

Bacterial type IV secretion (T4S) systems mediate the transfer of macromolecular substrates into various target cells, e.g., the conjugative transfer of DNA into bacteria or the transfer of virulence proteins into eukaryotic host cells. The T4S apparatus VirB of the vascular tumor-inducing pathogen Bartonella henselae causes subversion of human endothelial cell (HEC) function. Here we report the identification of multiple protein substrates of VirB, which, upon translocation into HEC, mediate all known VirB-dependent cellular changes. These Bartonella-translocated effector proteins (Beps) A-G are encoded together with the VirB system and the T4S coupling protein VirD4 on a Bartonella-specific pathogenicity island. The Beps display a modular architecture, suggesting an evolution by extensive domain duplication and reshuffling. The C terminus of each Bep harbors at least one copy of the Bep-intracellular delivery domain and a short positively charged tail sequence. This biparte C terminus constitutes a transfer signal that is sufficient to mediate VirB/VirD4-dependent intracellular delivery of reporter protein fusions. The Bep-intracellular delivery domain is also present in conjugative relaxases of bacterial conjugation systems. We exemplarily show that the C terminus of such a conjugative relaxase mediates protein transfer through the Bartonella henselae VirB/VirD4 system into HEC. Conjugative relaxases may thus represent the evolutionary origin of the here defined T4S signal for protein transfer into human cells. PMID:15642951

Structural insights into electron transfer in caa3-type cytochrome oxidase

PubMed Central

Lyons, Joseph A.; Aragão, David; Slattery, Orla; Pisliakov, Andrei V.; Soulimane, Tewfik; Caffrey, Martin

2012-01-01

Summary Paragraph Cytochrome c oxidase is a member of the heme copper oxidase superfamily (HCO)1. HCOs function as the terminal enzymes in the respiratory chain of mitochondria and aerobic prokaryotes, coupling molecular oxygen reduction to transmembrane proton pumping. Integral to the enzyme’s function is the transfer of electrons from cytochrome c to the oxidase via a transient association of the two proteins. Electron entry and exit are proposed to occur from the same site on cytochrome c2–4. Here we report the crystal structure of the caa3-type cytochrome oxidase from Thermus thermophilus, which has a covalently tethered cytochrome c domain. Crystals were grown in a bicontinuous mesophase using a synthetic short-chain monoacylglycerol as the hosting lipid. From the electron density map, at 2.36 Å resolution, a novel integral membrane subunit and a native glycoglycerophospholipid embedded in the complex were identified. Contrary to previous electron transfer mechanisms observed for soluble cytochrome c, the structure reveals the architecture of the electron transfer complex for the fused cupredoxin/cytochrome c domain which implicates different sites on cytochrome c for electron entry and exit. Support for an alternative to the classical proton gate characteristic of this HCO class is presented. PMID:22763450

Development of the Complex General Linear Model in the Fourier Domain: Application to fMRI Multiple Input-Output Evoked Responses for Single Subjects

PubMed Central

Rio, Daniel E.; Rawlings, Robert R.; Woltz, Lawrence A.; Gilman, Jodi; Hommer, Daniel W.

2013-01-01

A linear time-invariant model based on statistical time series analysis in the Fourier domain for single subjects is further developed and applied to functional MRI (fMRI) blood-oxygen level-dependent (BOLD) multivariate data. This methodology was originally developed to analyze multiple stimulus input evoked response BOLD data. However, to analyze clinical data generated using a repeated measures experimental design, the model has been extended to handle multivariate time series data and demonstrated on control and alcoholic subjects taken from data previously analyzed in the temporal domain. Analysis of BOLD data is typically carried out in the time domain where the data has a high temporal correlation. These analyses generally employ parametric models of the hemodynamic response function (HRF) where prewhitening of the data is attempted using autoregressive (AR) models for the noise. However, this data can be analyzed in the Fourier domain. Here, assumptions made on the noise structure are less restrictive, and hypothesis tests can be constructed based on voxel-specific nonparametric estimates of the hemodynamic transfer function (HRF in the Fourier domain). This is especially important for experimental designs involving multiple states (either stimulus or drug induced) that may alter the form of the response function. PMID:23840281

Development of the complex general linear model in the Fourier domain: application to fMRI multiple input-output evoked responses for single subjects.

PubMed

Rio, Daniel E; Rawlings, Robert R; Woltz, Lawrence A; Gilman, Jodi; Hommer, Daniel W

2013-01-01

A linear time-invariant model based on statistical time series analysis in the Fourier domain for single subjects is further developed and applied to functional MRI (fMRI) blood-oxygen level-dependent (BOLD) multivariate data. This methodology was originally developed to analyze multiple stimulus input evoked response BOLD data. However, to analyze clinical data generated using a repeated measures experimental design, the model has been extended to handle multivariate time series data and demonstrated on control and alcoholic subjects taken from data previously analyzed in the temporal domain. Analysis of BOLD data is typically carried out in the time domain where the data has a high temporal correlation. These analyses generally employ parametric models of the hemodynamic response function (HRF) where prewhitening of the data is attempted using autoregressive (AR) models for the noise. However, this data can be analyzed in the Fourier domain. Here, assumptions made on the noise structure are less restrictive, and hypothesis tests can be constructed based on voxel-specific nonparametric estimates of the hemodynamic transfer function (HRF in the Fourier domain). This is especially important for experimental designs involving multiple states (either stimulus or drug induced) that may alter the form of the response function.

Autonomous Frequency Domain Identification: Theory and Experiment

DTIC Science & Technology

1989-04-15

4,4,3)). This approach is particularly well suited to provide accurate estimation using sampled-data -3 DO 2 ^ UJ H « > x 2 ^ ui M (d 5 -P m...criteria for resonance requires a unimodal search. Search strategies such as golden search, Fibonacci search etc. are well known and can be found for...identified nonparametrically and a frequency domain de - scription is available, a parametric representation of the transfer function can be found by

Accelerating Imitation Learning in Relational Domains via Transfer by Initialization

DTIC Science & Technology

2013-08-28

Warcraft , regulation of traffic lights, logistics, and a variety of planning domains. A supervised learning method for imitation learning was recently...some information about the world (traffic density at a signal, distance to the goal etc.). We assume a functional parametrization over the policy and...strategy (RTS) game engine written in C based off the Warcraft series of games. Like all RTS games, it allows multiple agents to be controlled

Tuning BRCA1 and BARD1 activity to investigate RING ubiquitin ligase mechanisms.

PubMed

Stewart, Mikaela D; Duncan, Emily D; Coronado, Ernesto; DaRosa, Paul A; Pruneda, Jonathan N; Brzovic, Peter S; Klevit, Rachel E

2017-03-01

The tumor-suppressor protein BRCA1 works with BARD1 to catalyze the transfer of ubiquitin onto protein substrates. The N-terminal regions of BRCA1 and BARD1 that contain their RING domains are responsible for dimerization and ubiquitin ligase activity. This activity is a common feature among hundreds of human RING domain-containing proteins. RING domains bind and activate E2 ubiquitin-conjugating enzymes to promote ubiquitin transfer to substrates. We show that the identity of residues at specific positions in the RING domain can tune activity levels up or down. We report substitutions that create a structurally intact BRCA1/BARD1 heterodimer that is inactive in vitro with all E2 enzymes. Other substitutions in BRCA1 or BARD1 RING domains result in hyperactivity, revealing that both proteins have evolved attenuated activity. Loss of attenuation results in decreased product specificity, providing a rationale for why nature has tuned BRCA1 activity. The ability to tune BRCA1 provides powerful tools for understanding its biological functions and provides a basis to assess mechanisms for rescuing the activity of cancer-associated variations. Beyond the applicability to BRCA1, we show the identity of residues at tuning positions that can be used to predict and modulate the activity of an unrelated RING E3 ligase. These findings provide valuable insights into understanding the mechanism and function of RING E3 ligases like BRCA1. © 2017 The Protein Society.

Comparative Genomic Analyses of the Bacterial Phosphotransferase System

PubMed Central

Barabote, Ravi D.; Saier, Milton H.

2005-01-01

We report analyses of 202 fully sequenced genomes for homologues of known protein constituents of the bacterial phosphoenolpyruvate-dependent phosphotransferase system (PTS). These included 174 bacterial, 19 archaeal, and 9 eukaryotic genomes. Homologues of PTS proteins were not identified in archaea or eukaryotes, showing that the horizontal transfer of genes encoding PTS proteins has not occurred between the three domains of life. Of the 174 bacterial genomes (136 bacterial species) analyzed, 30 diverse species have no PTS homologues, and 29 species have cytoplasmic PTS phosphoryl transfer protein homologues but lack recognizable PTS permeases. These soluble homologues presumably function in regulation. The remaining 77 species possess all PTS proteins required for the transport and phosphorylation of at least one sugar via the PTS. Up to 3.2% of the genes in a bacterium encode PTS proteins. These homologues were analyzed for family association, range of protein types, domain organization, and organismal distribution. Different strains of a single bacterial species often possess strikingly different complements of PTS proteins. Types of PTS protein domain fusions were analyzed, showing that certain types of domain fusions are common, while others are rare or prohibited. Select PTS proteins were analyzed from different phylogenetic standpoints, showing that PTS protein phylogeny often differs from organismal phylogeny. The results document the frequent gain and loss of PTS protein-encoding genes and suggest that the lateral transfer of these genes within the bacterial domain has played an important role in bacterial evolution. Our studies provide insight into the development of complex multicomponent enzyme systems and lead to predictions regarding the types of protein-protein interactions that promote efficient PTS-mediated phosphoryl transfer. PMID:16339738

The effects of video-game training on broad cognitive transfer in multiple sclerosis: A pilot randomized controlled trial.

PubMed

Janssen, Alisha; Boster, Aaron; Lee, HyunKyu; Patterson, Beth; Prakash, Ruchika Shaurya

2015-01-01

Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system that results in diffuse nerve damage and associated physical and cognitive impairments. Of the few comprehensive rehabilitation options that exist for populations with lower baseline cognitive functioning, those that have been successful at eliciting broad cognitive improvements have focused on a multimodal training approach, emphasizing complex cognitive processing that utilizes multiple domains simultaneously. The current study sought to determine the feasibility of an 8-week, hybrid-variable priority training (HVT) program, with a secondary aim to assess the success of this training paradigm at eliciting broad cognitive transfer effects. Capitalizing on the multimodal training modalities offered by the Space Fortress platform, we compared the HVT strategy-based intervention with a waitlist control group, to primarily assess skill acquisition and secondarily determine presence of cognitive transfer. Twenty-eight participants met inclusionary criteria for the study and were randomized to either training or waitlist control groups. To assess broad transfer effects, a battery of neuropsychological tests was administered pre- and post-intervention. The results indicated an overall improvement in skill acquisition and evidence for the feasibility of the intervention, but a lack of broad transfer to tasks of cognitive functioning. Participants in the training group, however, did show improvements on a measure of spatial short-term memory. The current investigation provided support for the feasibility of a multimodal training approach, using the HVT strategy, within the MS population, but lacked broad transfer to multiple domains of cognitive functioning. Future improvements to obtain greater cognitive transfer efficacy would include a larger sample size, a longer course of training to evoke greater game score improvement, the inclusion of only cognitively impaired individuals, and integration of subjective measures of improvement in addition to objective tests of cognitive performance.

The phosphatidylinositol transfer protein RdgBβ binds 14-3-3 via its unstructured C-terminus, whereas its lipid-binding domain interacts with the integral membrane protein ATRAP (angiotensin II type I receptor-associated protein).

PubMed

Garner, Kathryn; Li, Michelle; Ugwuanya, Natalie; Cockcroft, Shamshad

2011-10-01

PITPs [PI (phosphatidylinositol) transfer proteins] bind and transfer PI between intracellular membranes and participate in many cellular processes including signalling, lipid metabolism and membrane traffic. The largely uncharacterized PITP RdgBβ (PITPNC1; retinal degeneration type B β), contains a long C-terminal disordered region following its defining N-terminal PITP domain. In the present study we report that the C-terminus contains two tandem phosphorylated binding sites (Ser(274) and Ser(299)) for 14-3-3. The C-terminus also contains PEST sequences which are shielded by 14-3-3 binding. Like many proteins containing PEST sequences, the levels of RdgBβ are regulated by proteolysis. RdgBβ is degraded with a half-life of 4 h following ubiquitination via the proteasome. A mutant RdgBβ which is unable to bind 14-3-3 is degraded even faster with a half-life of 2 h. In vitro, RdgBβ is 100-fold less active than PITPα for PI transfer, and RdgBβ proteins (wild-type and a mutant that cannot bind 14-3-3) expressed in COS-7 cells or endogenous proteins from heart cytosol do not exhibit transfer activity. When cells are treated with PMA, the PITP domain of RdgBβ interacts with the integral membrane protein ATRAP (angiotensin II type I receptor-associated protein; also known as AGTRAP) causing membrane recruitment. We suggest that RdgBβ executes its function following recruitment to membranes via its PITP domain and the C-terminal end of the protein could regulate entry to the hydrophobic cavity.

Effects of local thermodynamics and of stellar mass ratio on accretion disc stability in close binaries

NASA Astrophysics Data System (ADS)

Lanzafame, G.

2009-08-01

Inflow kinematics at the inner Lagrangian point L1, gas compressibility, and physical turbulent viscosity play a fundamental role on accretion disc dynamics and structure in a close binary (CB). Physical viscosity supports the accretion disc development inside the primary gravitational potential well, developing the gas radial transport, converting mechanical energy into heat. The Stellar-Mass-Ratio (SMR) between the compact primary and the secondary star (M1/M2) is also effective, not only in the location of the inner Lagrangian point, but also in the angular kinematics of the mass transfer and in the geometry of the gravitational potential wells. In this work we pay attention in particular to the role of the SMR, evaluating boundaries, separating theoretical domains in compressibility-viscosity graphs where physical conditions allow a well-bound disc development, as a function of mass transfer kinematic conditions. In such domains, the lower is the gas compressibility (the higher the polytropic index γ), the higher is the physical viscosity (α) requested. In this work, we show how the boundaries of such domains vary as a function of M1/M2. Conclusions as far as dwarf novae outbursts are concerned, induced by mass transfer rate variations, are also reported. The smaller M1/M2, the shorter the duration of the active-to-quiet and vice-versa transitional phases. Time-scales are of the order of outburst duration of SU Uma, OY Car, Z Cha and SS Cyg-like objects. Moreover, conclusions as far as active-quiet-active phenomena in a CB, according to viscous-thermal instabilities, in accordance to such domains, are also reported.

Accurate calibration of waveform data measured by the Plasma Wave Experiment on board the ARASE satellite

NASA Astrophysics Data System (ADS)

Kitahara, M.; Katoh, Y.; Hikishima, M.; Kasahara, Y.; Matsuda, S.; Kojima, H.; Ozaki, M.; Yagitani, S.

2017-12-01

The Plasma Wave Experiment (PWE) is installed on board the ARASE satellite to measure the electric field in the frequency range from DC to 10 MHz, and the magnetic field in the frequency range from a few Hz to 100 kHz using two dipole wire-probe antennas (WPT) and three magnetic search coils (MSC), respectively. In particular, the Waveform Capture (WFC), one of the receivers of the PWE, can detect electromagnetic field waveform in the frequency range from a few Hz to 20 kHz. The Software-type Wave Particle Interaction Analyzer (S-WPIA) is installed on the ARASE satellite to measure the energy exchange between plasma waves and particles. Since S-WPIA uses the waveform data measured by WFC to calculate the relative phase angle between the wave magnetic field and velocity of energetic electrons, the high-accuracy is required to calibration of both amplitude and phase of the waveform data. Generally, the calibration procedure of the signal passed through a receiver consists of three steps; the transformation into spectra, the calibration by the transfer function of a receiver, and the inverse transformation of the calibrated spectra into the time domain. Practically, in order to reduce the side robe effect, a raw data is filtered by a window function in the time domain before applying Fourier transform. However, for the case that a first order differential coefficient of the phase transfer function of the system is not negligible, the phase of the window function convoluted into the calibrated spectra is shifted differently at each frequency, resulting in a discontinuity in the time domain of the calibrated waveform data. To eliminate the effect of the phase shift of a window function, we suggest several methods to calibrate a waveform data accurately and carry out simulations assuming simple sinusoidal waves as an input signal and using transfer functions of WPT, MSC, and WFC obtained in pre-flight tests. In consequence, we conclude that the following two methods can reduce an error contaminated through the calibration to less than 0.1 % of amplitude of input waves; (1) a Turkey-type window function with a flat top region of one-third of the window length and (2) modification of the window function for each frequency by referring the estimation of the phase shift due to the first order differential coefficient from the transfer functions.

DEER distance measurement between a spin label and a native FAD semiquinone in electron transfer flavoprotein.

PubMed

Swanson, Michael A; Kathirvelu, Velavan; Majtan, Tomas; Frerman, Frank E; Eaton, Gareth R; Eaton, Sandra S

2009-11-11

The human mitochondrial electron transfer flavoprotein (ETF) accepts electrons from at least 10 different flavoprotein dehydrogenases and transfers electrons to a single electron acceptor in the inner membrane. Paracoccus denitrificans ETF has the identical function, shares the same three-dimensional structure and functional domains, and exhibits the same conformational mobility. It has been proposed that the mobility of the alphaII domain permits the promiscuous behavior of ETF with respect to a variety of redox partners. Double electron-electron resonance (DEER) measurements between a spin label and an enzymatically reduced flavin adenine dinucleotide (FAD) cofactor in P. denitrificans ETF gave two distributions of distances: a major component centered at 4.2 +/- 0.1 nm and a minor component centered at 5.1 +/- 0.2 nm. Both components had widths of approximately 0.3 nm. A distance of 4.1 nm was calculated using the crystal structure of P. denitrificans ETF, which agrees with the major component obtained from the DEER measurement. The observation of a second distribution suggests that ETF, in the absence of substrate, adopts some conformations that are intermediate between the predominant free and substrate-bound states.

DEER Distance Measurement Between a Spin Label and a Native FAD Semiquinone in Electron Transfer Flavoprotein

PubMed Central

Swanson, Michael A.; Kathirvelu, Velavan; Majtan, Tomas; Frerman, Frank E.; Eaton, Gareth R.; Eaton, Sandra S.

2009-01-01

The human mitochondrial electron transfer flavoprotein (ETF) accepts electrons from at least 10 different flavoprotein dehydrogenases and transfers electrons to a single electron acceptor in the inner membrane. Paracoccus denitrificans ETF has the identical function, shares the same three dimensional structure and functional domains, and exhibits the same conformational mobility. It has been proposed that the mobility of the αII domain permits the promiscuous behavior of ETF with respect to a variety of redox partners. Double electron-electron resonance (DEER) measurements between a spin label and an enzymatically reduced flavin adenine dinucleotide (FAD) cofactor in P. denitrificans ETF gave two distributions of distances: a major component centered at 4.2 ± 0.1 nm and a minor component centered at 5.1 ± 0.2 nm. Both components had widths of approximately 0.3 nm. A distance of 4.1 nm was calculated using the crystal structure of P. denitrificans ETF, which agrees with the major component obtained from the DEER measurement. The observation of a second distribution suggests that ETF, in the absence of substrate, adopts some conformations that are intermediate between the predominant free and substrate-bound states. PMID:19886689

Building the analytical response in frequency domain of AC biased bolometers. Application to Planck/HFI

NASA Astrophysics Data System (ADS)

Sauvé, Alexandre; Montier, Ludovic

2016-12-01

Context: Bolometers are high sensitivity detector commonly used in Infrared astronomy. The HFI instrument of the Planck satellite makes extensive use of them, but after the satellite launch two electronic related problems revealed critical. First an unexpected excess response of detectors at low optical excitation frequency for ν < 1 Hz, and secondly the Analog To digital Converter (ADC) component had been insufficiently characterized on-ground. These two problems require an exquisite knowledge of detector response. However bolometers have highly nonlinear characteristics, coming from their electrical and thermal coupling making them very difficult to model. Goal: We present a method to build the analytical transfer function in frequency domain which describe the voltage response of an Alternative Current (AC) biased bolometer to optical excitation, based on the standard bolometer model. This model is built using the setup of the Planck/HFI instrument and offers the major improvement of being based on a physical model rather than the currently in use had-hoc model based on Direct Current (DC) bolometer theory. Method: The analytical transfer function expression will be presented in matrix form. For this purpose, we build linearized versions of the bolometer electro thermal equilibrium. A custom description of signals in frequency is used to solve the problem with linear algebra. The model performances is validated using time domain simulations. Results: The provided expression is suitable for calibration and data processing. It can also be used to provide constraints for fitting optical transfer function using real data from steady state electronic response and optical response. The accurate description of electronic response can also be used to improve the ADC nonlinearity correction for quickly varying optical signals.

Signal transduction and phosphoryl transfer by a FixL hybrid kinase with low oxygen affinity: importance of the vicinal PAS domain and receiver aspartate.

PubMed

Sousa, Eduardo H S; Tuckerman, Jason R; Gondim, Ana C S; Gonzalez, Gonzalo; Gilles-Gonzalez, Marie-Alda

2013-01-22

FixL is a prototype for heme-based sensors, multidomain proteins that typically couple a histidine protein kinase activity to a heme-binding domain for sensing of diatomic gases such as oxygen, carbon monoxide, and nitric oxide. Despite the relatively well-developed understanding of FixL, the importance of some of its domains has been unclear. To explore the impact of domain-domain interactions on oxygen sensing and signal transduction, we characterized and investigated Rhizobium etli hybrid sensor ReFixL. In ReFixL, the core heme-containing PAS domain and kinase region is preceded by an N-terminal PAS domain of unknown function and followed by a C-terminal receiver domain. The latter resembles a target substrate domain that usually occurs independently of the kinase and contains a phosphorylatable aspartate residue. We isolated the full-length ReFixL as a soluble holoprotein with a single heme b cofactor. Despite a low affinity for oxygen (K(d) for O₂ of 738 μM), the kinase activity was completely switched off by O₂ at concentrations well below the K(d). A deletion of the first PAS domain strongly increased the oxygen affinity but essentially prohibited autophosphorylation, although the truncated protein was competent to accept phosphoryl groups in trans. These studies provide new insights into histidyl-aspartyl phosphoryl transfers in two-component systems and suggest that the control of ligand affinity and signal transduction by PAS domains can be direct or indirect.

Transfer of Kv3.1 voltage sensor features to the isolated Ci-VSP voltage-sensing domain.

PubMed

Mishina, Yukiko; Mutoh, Hiroki; Knöpfel, Thomas

2012-08-22

Membrane proteins that respond to changes in transmembrane voltage are critical in regulating the function of living cells. The voltage-sensing domains (VSDs) of voltage-gated ion channels are extensively studied to elucidate voltage-sensing mechanisms, and yet many aspects of their structure-function relationship remain elusive. Here, we transplanted homologous amino acid motifs from the tetrameric voltage-activated potassium channel Kv3.1 to the monomeric VSD of Ciona intestinalis voltage-sensitive phosphatase (Ci-VSP) to explore which portions of Kv3.1 subunits depend on the tetrameric structure of Kv channels and which properties of Kv3.1 can be transferred to the monomeric Ci-VSP scaffold. By attaching fluorescent proteins to these chimeric VSDs, we obtained an optical readout to establish membrane trafficking and kinetics of voltage-dependent structural rearrangements. We found that motifs extending from 10 to roughly 100 amino acids can be readily transplanted from Kv3.1 into Ci-VSP to form engineered VSDs that efficiently incorporate into the plasma membrane and sense voltage. Some of the functional features of these engineered VSDs are reminiscent of Kv3.1 channels, indicating that these properties do not require interactions between Kv subunits or between the voltage sensing and the pore domains of Kv channels. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Chirped-pulse coherent-OTDR with predistortion

NASA Astrophysics Data System (ADS)

Xiong, Ji; Jiang, Jialin; Wu, Yue; Chen, Yongxiang; Xie, Lianlian; Fu, Yun; Wang, Zinan

2018-03-01

In this paper, a novel method for generating high-quality chirped pulses with IQ modulator is studied theoretically and experimentally, which is a crucial building block for high-performance coherent optical time-domain reflectometry (COTDR). In order to compensate the nonlinearity of the modulator transfer function, we present a predistortion technique for chirped-pulse coherent optical time-domain reflectometry (CP-COTDR), the arcsin predistortion method and the single sideband with a suppressed carrier analog modulation used to generate the high quality chirped optical pulse. The high order sidebands, due to the large amplitude of the modulation signal and the nonlinear transfer function of the IQ modulator, can be relieved by the predistortion process, which means the power and the quality of the generated chirped pulse has been improved. In the experiment, this method increases the peak power of the chirped pulse by 4.2 dB compared to the case without predistortion process, as for the CP-COTDR system, this method increases the signal-to-noise ratio of the demodulated phase variation by 6.3 dB.

Printing Functional 3D Microdevices by Laser-Induced Forward Transfer.

PubMed

Luo, Jun; Pohl, Ralph; Qi, Lehua; Römer, Gert-Willem; Sun, Chao; Lohse, Detlef; Visser, Claas Willem

2017-03-01

Slender, out-of-plane metal microdevices are made in a new spatial domain, by using laser-induced forward transfer (LIFT) of metals. Here, a thermocouple with a thickness of 10 µm and a height of 250 µm, consisting of platinum and gold pillars is demonstrated. Multimaterial LIFT enables manufacturing in the micrometer to millimeter range, i.e., between lithography and other 3D printing technologies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Factors influencing training transfer in nursing profession: a qualitative study.

PubMed

Ma, Fang; Bai, Yangjing; Bai, Yangjuan; Ma, Weiguang; Yang, Xiangyu; Li, Jiping

2018-03-20

There is a growing recognition that training is not translated into performance and the 'transfer problem' exists in organization training today. Although factors contributing to training transfer have been identified in business and industry, the factors influencing training transfer in nursing profession remain less clear. A qualitative descriptive study was undertaken in two tertiary referral hospitals in China from February 2013 to September 2013. Purposeful sampling of 24 nursing staffs were interviewed about the factors influencing training transfer. Seven themes evolved from the analysis, categorized in 4 main domains, which described the factors influencing training transfer in nursing profession in trainee characteristics, training design, work environment and profession domain. The trainee characteristics domain included attitude and ability. The training design domain included training content and instruction method. The work environment domain included supports as facilitators and opposition as hindrance. The theme pertaining to the profession domain was professional development. Health care managers need to understand the factors influencing training transfer for maximizing the benefits of training. The right beliefs and values about training, the rigorous employee selection for training, the relevance of training content, training instructions facilitating learning and transfer, supports from peer, supervisors and the organization, organizational culture such as change, sharing, learning and support, and professional development are key to successful training transfer. Furthermore, managers should be aware of the opposition from co-workers and find ways to prevent it.

Heat transfer characteristics within an array of impinging jets. Effects of crossflow temperature relative to jet temperature

NASA Technical Reports Server (NTRS)

Florschuetz, L. W.; Su, C. C.

1985-01-01

Spanwise average heat fluxes, resolved in the streamwise direction to one stream-wise hole spacing were measured for two-dimensional arrays of circular air jets impinging on a heat transfer surface parallel to the jet orifice plate. The jet flow, after impingement, was constrained to exit in a single direction along the channel formed by the jet orifice plate and heat transfer surface. The crossflow originated from the jets following impingement and an initial crossflow was present that approached the array through an upstream extension of the channel. The regional average heat fluxes are considered as a function of parameters associated with corresponding individual spanwise rows within the array. A linear superposition model was employed to formulate appropriate governing parameters for the individual row domain. The effects of flow history upstream of an individual row domain are also considered. The results are formulated in terms of individual spanwise row parameters. A corresponding set of streamwise resolved heat transfer characteristics formulated in terms of flow and geometric parameters characterizing the overall arrays is described.

Shared acoustic codes underlie emotional communication in music and speech—Evidence from deep transfer learning

PubMed Central

Schuller, Björn

2017-01-01

Music and speech exhibit striking similarities in the communication of emotions in the acoustic domain, in such a way that the communication of specific emotions is achieved, at least to a certain extent, by means of shared acoustic patterns. From an Affective Sciences points of view, determining the degree of overlap between both domains is fundamental to understand the shared mechanisms underlying such phenomenon. From a Machine learning perspective, the overlap between acoustic codes for emotional expression in music and speech opens new possibilities to enlarge the amount of data available to develop music and speech emotion recognition systems. In this article, we investigate time-continuous predictions of emotion (Arousal and Valence) in music and speech, and the Transfer Learning between these domains. We establish a comparative framework including intra- (i.e., models trained and tested on the same modality, either music or speech) and cross-domain experiments (i.e., models trained in one modality and tested on the other). In the cross-domain context, we evaluated two strategies—the direct transfer between domains, and the contribution of Transfer Learning techniques (feature-representation-transfer based on Denoising Auto Encoders) for reducing the gap in the feature space distributions. Our results demonstrate an excellent cross-domain generalisation performance with and without feature representation transfer in both directions. In the case of music, cross-domain approaches outperformed intra-domain models for Valence estimation, whereas for Speech intra-domain models achieve the best performance. This is the first demonstration of shared acoustic codes for emotional expression in music and speech in the time-continuous domain. PMID:28658285

Shared acoustic codes underlie emotional communication in music and speech-Evidence from deep transfer learning.

PubMed

Coutinho, Eduardo; Schuller, Björn

2017-01-01

Music and speech exhibit striking similarities in the communication of emotions in the acoustic domain, in such a way that the communication of specific emotions is achieved, at least to a certain extent, by means of shared acoustic patterns. From an Affective Sciences points of view, determining the degree of overlap between both domains is fundamental to understand the shared mechanisms underlying such phenomenon. From a Machine learning perspective, the overlap between acoustic codes for emotional expression in music and speech opens new possibilities to enlarge the amount of data available to develop music and speech emotion recognition systems. In this article, we investigate time-continuous predictions of emotion (Arousal and Valence) in music and speech, and the Transfer Learning between these domains. We establish a comparative framework including intra- (i.e., models trained and tested on the same modality, either music or speech) and cross-domain experiments (i.e., models trained in one modality and tested on the other). In the cross-domain context, we evaluated two strategies-the direct transfer between domains, and the contribution of Transfer Learning techniques (feature-representation-transfer based on Denoising Auto Encoders) for reducing the gap in the feature space distributions. Our results demonstrate an excellent cross-domain generalisation performance with and without feature representation transfer in both directions. In the case of music, cross-domain approaches outperformed intra-domain models for Valence estimation, whereas for Speech intra-domain models achieve the best performance. This is the first demonstration of shared acoustic codes for emotional expression in music and speech in the time-continuous domain.

A general transfer-function approach to noise filtering in open-loop quantum control

NASA Astrophysics Data System (ADS)

Viola, Lorenza

2015-03-01

Hamiltonian engineering via unitary open-loop quantum control provides a versatile and experimentally validated framework for manipulating a broad class of non-Markovian open quantum systems of interest, with applications ranging from dynamical decoupling and dynamically corrected quantum gates, to noise spectroscopy and quantum simulation. In this context, transfer-function techniques directly motivated by control engineering have proved invaluable for obtaining a transparent picture of the controlled dynamics in the frequency domain and for quantitatively analyzing performance. In this talk, I will show how to identify a computationally tractable set of ``fundamental filter functions,'' out of which arbitrary filter functions may be assembled up to arbitrary high order in principle. Besides avoiding the infinite recursive hierarchy of filter functions that arises in general control scenarios, this fundamental set suffices to characterize the error suppression capabilities of the control protocol in both the time and frequency domain. I will show, in particular, how the resulting notion of ``filtering order'' reveals conceptually distinct, albeit complementary, features of the controlled dynamics as compared to the ``cancellation order,'' traditionally defined in the Magnus sense. Implications for current quantum control experiments will be discussed. Work supported by the U.S. Army Research Office under Contract No. W911NF-14-1-0682.

Structural dynamics of catalytic RNA highlighted by fluorescence resonance energy transfer.

PubMed

Walter, N G

2001-09-01

RNA performs a multitude of essential cellular functions involving the maintenance, transfer, and processing of genetic information. The reason probably is twofold: (a) Life started as a prebiotic RNA World, in which RNA served as the genetic information carrier and catalyzed all chemical reactions required for its proliferation and (b) some of the RNA World functions were conserved throughout evolution because neither DNA nor protein is as adept in fulfilling them. A particular advantage of RNA is its high propensity to form alternative structures as required in subsequent steps of a reaction pathway. Here I describe fluorescence resonance energy transfer (FRET) as a method to monitor a crucial conformational transition on the reaction pathway of the hairpin ribozyme, a small catalytic RNA motif from a self-replicating plant virus satellite RNA and well-studied paradigm of RNA folding. Steady-state FRET measurements in solution allow one to measure the kinetics and requirements of docking of its two independently folding domains; time-resolved FRET reveals the relative thermodynamic stability of the undocked (extended, inactive) and docked (active) ribozyme conformations; while single-molecule FRET experiments will highlight the dynamics of RNA at the individual molecule level. Similar domain docking events are expected to be at the heart of many biological functions of RNA, and the described FRET techniques promise to be adaptable to most of the involved RNA systems. Copyright 2001 Academic Press.

Parkin-catalyzed Ubiquitin-Ester Transfer Is Triggered by PINK1-dependent Phosphorylation*

PubMed Central

Iguchi, Masahiro; Kujuro, Yuki; Okatsu, Kei; Koyano, Fumika; Kosako, Hidetaka; Kimura, Mayumi; Suzuki, Norihiro; Uchiyama, Shinichiro; Tanaka, Keiji; Matsuda, Noriyuki

2013-01-01

PINK1 and PARKIN are causal genes for autosomal recessive familial Parkinsonism. PINK1 is a mitochondrial Ser/Thr kinase, whereas Parkin functions as an E3 ubiquitin ligase. Under steady-state conditions, Parkin localizes to the cytoplasm where its E3 activity is repressed. A decrease in mitochondrial membrane potential triggers Parkin E3 activity and recruits it to depolarized mitochondria for ubiquitylation of mitochondrial substrates. The molecular basis for how the E3 activity of Parkin is re-established by mitochondrial damage has yet to be determined. Here we provide in vitro biochemical evidence for ubiquitin-thioester formation on Cys-431 of recombinant Parkin. We also report that Parkin forms a ubiquitin-ester following a decrease in mitochondrial membrane potential in cells, and that this event is essential for substrate ubiquitylation. Importantly, the Parkin RING2 domain acts as a transthiolation or acyl-transferring domain rather than an E2-recruiting domain. Furthermore, formation of the ubiquitin-ester depends on PINK1 phosphorylation of Parkin Ser-65. A phosphorylation-deficient mutation completely inhibited formation of the Parkin ubiquitin-ester intermediate, whereas phosphorylation mimics, such as Ser to Glu substitution, enabled partial formation of the intermediate irrespective of Ser-65 phosphorylation. We propose that PINK1-dependent phosphorylation of Parkin leads to the ubiquitin-ester transfer reaction of the RING2 domain, and that this is an essential step in Parkin activation. PMID:23754282

Regulation of StAR by the N-terminal Domain and Coinduction of SIK1 and TIS11b/Znf36l1 in Single Cells

PubMed Central

Lee, Jinwoo; Tong, Tiegang; Duan, Haichuan; Foong, Yee Hoon; Musaitif, Ibrahim; Yamazaki, Takeshi; Jefcoate, Colin

2016-01-01

The cholesterol transfer function of steroidogenic acute regulatory protein (StAR) is uniquely integrated into adrenal cells, with mRNA translation and protein kinase A (PKA) phosphorylation occurring at the mitochondrial outer membrane (OMM). The StAR C-terminal cholesterol-binding domain (CBD) initiates mitochondrial intermembrane contacts to rapidly direct cholesterol to Cyp11a1 in the inner membrane (IMM). The conserved StAR N-terminal regulatory domain (NTD) includes a leader sequence targeting the CBD to OMM complexes that initiate cholesterol transfer. Here, we show how the NTD functions to enhance CBD activity delivers more efficiently from StAR mRNA in adrenal cells, and then how two factors hormonally restrain this process. NTD processing at two conserved sequence sites is selectively affected by StAR PKA phosphorylation. The CBD functions as a receptor to stimulate the OMM/IMM contacts that mediate transfer. The NTD controls the transit time that integrates extramitochondrial StAR effects on cholesterol homeostasis with other mitochondrial functions, including ATP generation, inter-organelle fusion, and the major permeability transition pore in partnership with other OMM proteins. PKA also rapidly induces two additional StAR modulators: salt-inducible kinase 1 (SIK1) and Znf36l1/Tis11b. Induced SIK1 attenuates the activity of CRTC2, a key mediator of StAR transcription and splicing, but only as cAMP levels decline. TIS11b inhibits translation and directs the endonuclease-mediated removal of the 3.5-kb StAR mRNA. Removal of either of these functions individually enhances cAMP-mediated induction of StAR. High-resolution fluorescence in situ hybridization (HR-FISH) of StAR RNA reveals asymmetric transcription at the gene locus and slow RNA splicing that delays mRNA formation, potentially to synchronize with cholesterol import. Adrenal cells may retain slow transcription to integrate with intermembrane NTD activation. HR-FISH resolves individual 3.5-kb StAR mRNA molecules via dual hybridization at the 3′- and 5′-ends and reveals an unexpectedly high frequency of 1:1 pairing with mitochondria marked by the matrix StAR protein. This pairing may be central to translation-coupled cholesterol transfer. Altogether, our results show that adrenal cells exhibit high-efficiency StAR activity that needs to integrate rapid cholesterol transfer with homeostasis and pulsatile hormonal stimulation. StAR NBD, the extended 3.5-kb mRNA, SIK1, and Tis11b play important roles. PMID:27531991

Regulation of StAR by the N-terminal Domain and Coinduction of SIK1 and TIS11b/Znf36l1 in Single Cells.

PubMed

Lee, Jinwoo; Tong, Tiegang; Duan, Haichuan; Foong, Yee Hoon; Musaitif, Ibrahim; Yamazaki, Takeshi; Jefcoate, Colin

2016-01-01

The cholesterol transfer function of steroidogenic acute regulatory protein (StAR) is uniquely integrated into adrenal cells, with mRNA translation and protein kinase A (PKA) phosphorylation occurring at the mitochondrial outer membrane (OMM). The StAR C-terminal cholesterol-binding domain (CBD) initiates mitochondrial intermembrane contacts to rapidly direct cholesterol to Cyp11a1 in the inner membrane (IMM). The conserved StAR N-terminal regulatory domain (NTD) includes a leader sequence targeting the CBD to OMM complexes that initiate cholesterol transfer. Here, we show how the NTD functions to enhance CBD activity delivers more efficiently from StAR mRNA in adrenal cells, and then how two factors hormonally restrain this process. NTD processing at two conserved sequence sites is selectively affected by StAR PKA phosphorylation. The CBD functions as a receptor to stimulate the OMM/IMM contacts that mediate transfer. The NTD controls the transit time that integrates extramitochondrial StAR effects on cholesterol homeostasis with other mitochondrial functions, including ATP generation, inter-organelle fusion, and the major permeability transition pore in partnership with other OMM proteins. PKA also rapidly induces two additional StAR modulators: salt-inducible kinase 1 (SIK1) and Znf36l1/Tis11b. Induced SIK1 attenuates the activity of CRTC2, a key mediator of StAR transcription and splicing, but only as cAMP levels decline. TIS11b inhibits translation and directs the endonuclease-mediated removal of the 3.5-kb StAR mRNA. Removal of either of these functions individually enhances cAMP-mediated induction of StAR. High-resolution fluorescence in situ hybridization (HR-FISH) of StAR RNA reveals asymmetric transcription at the gene locus and slow RNA splicing that delays mRNA formation, potentially to synchronize with cholesterol import. Adrenal cells may retain slow transcription to integrate with intermembrane NTD activation. HR-FISH resolves individual 3.5-kb StAR mRNA molecules via dual hybridization at the 3'- and 5'-ends and reveals an unexpectedly high frequency of 1:1 pairing with mitochondria marked by the matrix StAR protein. This pairing may be central to translation-coupled cholesterol transfer. Altogether, our results show that adrenal cells exhibit high-efficiency StAR activity that needs to integrate rapid cholesterol transfer with homeostasis and pulsatile hormonal stimulation. StAR NBD, the extended 3.5-kb mRNA, SIK1, and Tis11b play important roles.

Deep neural network-based domain adaptation for classification of remote sensing images

NASA Astrophysics Data System (ADS)

Ma, Li; Song, Jiazhen

2017-10-01

We investigate the effectiveness of deep neural network for cross-domain classification of remote sensing images in this paper. In the network, class centroid alignment is utilized as a domain adaptation strategy, making the network able to transfer knowledge from the source domain to target domain on a per-class basis. Since predicted labels of target data should be used to estimate the centroid of each class, we use overall centroid alignment as a coarse domain adaptation method to improve the estimation accuracy. In addition, rectified linear unit is used as the activation function to produce sparse features, which may improve the separation capability. The proposed network can provide both aligned features and an adaptive classifier, as well as obtain label-free classification of target domain data. The experimental results using Hyperion, NCALM, and WorldView-2 remote sensing images demonstrated the effectiveness of the proposed approach.

Cerebrovascular and cardiovascular variability interactions investigated through conditional joint transfer entropy in subjects prone to postural syncope.

PubMed

Bari, Vlasta; De Maria, Beatrice; Mazzucco, Claudio Enrico; Rossato, Gianluca; Tonon, Davide; Nollo, Giandomenico; Faes, Luca; Porta, Alberto

2017-05-01

A model-based conditional transfer entropy approach was exploited to quantify the information transfer in cerebrovascular (CBV) and cardiovascular (CV) systems in subjects prone to develop postural syncope. Spontaneous beat-to-beat variations of mean cerebral blood flow velocity (MCBFV) derived from a transcranial Doppler device, heart period (HP) derived from surface electrocardiogram, mean arterial pressure (MAP) and systolic arterial pressure (SAP) derived from finger plethysmographic arterial pressure device were monitored at rest in supine position (REST) and during 60° head-up tilt (TILT) in 13 individuals (age mean  ±  standard deviation: 28  ±  9 years, min-max range: 18-44 years, 5 males) with a history of recurrent episodes of syncope (SYNC) and in 13 age- and gender-matched controls (NonSYNC). Respiration (R) obtained from a thoracic belt was acquired as well and considered as a conditioning signal in transfer entropy assessment. Synchronous sequences of 250 consecutive MCBFV, HP, MAP, SAP and R values were utilized to estimate the information genuinely transferred from MAP to MCBFV (i.e. disambiguated from R influences) and vice versa. Analogous indexes were computed from SAP to HP and vice versa. Traditional time and frequency domain analyses were carried out as well. SYNC subjects showed an increased genuine information transfer from MAP to MCBFV during TILT, while they did not exhibit the expected rise of the genuine information transfer from SAP to HP. We conclude that SYNC individuals featured an impaired cerebral autoregulation visible during TILT and were unable to activate cardiac baroreflex to cope with the postural challenge. Traditional frequency domain markers based on transfer function modulus, phase and coherence functions were less powerful or less specific in typifying the CBV and CV controls of SYNC individuals. Conditional transfer entropy approach can identify the impairment of CBV and CV controls and provide specific clues to identify subjects prone to develop postural syncope.

Structural insights into a StART-like domain in Lam4 and its interaction with sterol ligands.

PubMed

Gatta, Alberto T; Sauerwein, Andrea C; Zhuravleva, Anastasia; Levine, Tim P; Matthews, Stephen

2018-01-15

Sterols are essential components of cellular membranes and shape their biophysical properties. The recently discovered family of Lipid transfer proteins Anchored at Membrane contact sites (LAMs) has been suggested to carry out intracellular sterol traffic using StART-like domains. Here, we studied the second StART-like domain of Lam4p from S. cerevisiae by NMR. We show that NMR data are consistent with the StART-like domain structure, and that several functionally important regions within the domain exhibit significant conformational dynamics. NMR titration experiments confirm sterol binding to the canonical sterol-binding site and suggest a role of membrane interactions on the thermodynamics and kinetics of sterol binding. Copyright © 2017 Elsevier Inc. All rights reserved.

Description of waves in inhomogeneous domains using Heun's equation

NASA Astrophysics Data System (ADS)

Bednarik, M.; Cervenka, M.

2018-04-01

There are a number of model equations describing electromagnetic, acoustic or quantum waves in inhomogeneous domains and some of them are of the same type from the mathematical point of view. This isomorphism enables us to use a unified approach to solving the corresponding equations. In this paper, the inhomogeneity is represented by a trigonometric spatial distribution of a parameter determining the properties of an inhomogeneous domain. From the point of view of modeling, this trigonometric parameter function can be smoothly connected to neighboring constant-parameter regions. For this type of distribution, exact local solutions of the model equations are represented by the local Heun functions. As the interval for which the solution is sought includes two regular singular points. For this reason, a method is proposed which resolves this problem only based on the local Heun functions. Further, the transfer matrix for the considered inhomogeneous domain is determined by means of the proposed method. As an example of the applicability of the presented solutions the transmission coefficient is calculated for the locally periodic structure which is given by an array of asymmetric barriers.

Which Factors Influence Functional Patients Improvements During Rehabilitation?

PubMed Central

Gabriele, Messina; Lorena, Rasimelli; Chiara, Bonavita; Emma, Ceriale; Cecilia, Quercioli; Nicola, Nante

2014-01-01

Background: Rehabilitation in patients with disabilities is an important aspect of tertiary prevention. Severity of disability, evaluated by global measures of autonomy, is essential for functional outcome evaluation. Aim: To determine the effectiveness of a rehabilitation programme in terms of percentage functional improvement (PFI); to verify the role of gender, age and length of stay (LOS), by motor and cognitive domains, on PFI. Design: Longitudinal study. Setting: An intensive rehabilitation hospital. Population: 305 inpatients. Methods: The disability has been investigated using the Functional Independence Measure (FIM). Percentage differences between discharge and admission were calculated for FIM score. Wilcoxon matched pair test for the six areas and the two domains of the FIM score were calculated. The effect of LOS, gender and age on PFI were studied with Robust regression. Results: Neurological and Orthopaedic patients had improvements on Motor and Cognitive domains. The greatest gains were in the Self Care, Sphintere Control, Transfer and Locomotion Areas (p=<0.001). LOS was associated (p<0.001) with PFI while age resulted borderline significant (p=0.049) in the cognitive domain in Neurological patients. Conclusion: The rehabilitation improved the overall conditions of neurological and orthopaedic patients. LOS emerged as the most important determinant in PFI. PMID:24762348

Conformational fluctuation of Synaptotagmin-1 observed with single molecule fluorescence resonance energy transfer (smFRET)

NASA Astrophysics Data System (ADS)

Choi, Ucheor; Weninger, Keith

2008-10-01

Calcium dependent neurotransmitter release at the synapses involves a synaptic vesicle protein synaptotagmin-1, a calcium sensor, to regulate exocytosis. It has been known that Synaptotagmin-1 interacts with assembled SNARE complexes, but it is unclear how their molecular mechanisms are coupled. X-ray studies in the absence of calcium revealed a closed conformation of synaptotagmin-1 and with calcium bound to the C2 domains of synaptotagmin-3 found extensive interactions holding the domains open. Suggesting the two conformations can be the key to the two functions of synaptotagmin in regulating neurotransmission. Here we use single molecule fluorescence resonance energy transfer (smFRET) to study synaptotagmin interactions with SNARE complexes and the spontaneous conformational changes of synaptotagmin-1 when calcium is induced.

Frequency domain system identification methods - Matrix fraction description approach

NASA Technical Reports Server (NTRS)

Horta, Luca G.; Juang, Jer-Nan

1993-01-01

This paper presents the use of matrix fraction descriptions for least-squares curve fitting of the frequency spectra to compute two matrix polynomials. The matrix polynomials are intermediate step to obtain a linearized representation of the experimental transfer function. Two approaches are presented: first, the matrix polynomials are identified using an estimated transfer function; second, the matrix polynomials are identified directly from the cross/auto spectra of the input and output signals. A set of Markov parameters are computed from the polynomials and subsequently realization theory is used to recover a minimum order state space model. Unevenly spaced frequency response functions may be used. Results from a simple numerical example and an experiment are discussed to highlight some of the important aspect of the algorithm.

ORP5/ORP8 localize to endoplasmic reticulum-mitochondria contacts and are involved in mitochondrial function.

PubMed

Galmes, Romain; Houcine, Audrey; van Vliet, Alexander R; Agostinis, Patrizia; Jackson, Catherine L; Giordano, Francesca

2016-06-01

The oxysterol-binding protein (OSBP)-related proteins ORP5 and ORP8 have been shown recently to transport phosphatidylserine (PS) from the endoplasmic reticulum (ER) to the plasma membrane (PM) at ER-PM contact sites. PS is also transferred from the ER to mitochondria where it acts as precursor for mitochondrial PE synthesis. Here, we show that, in addition to ER-PM contact sites, ORP5 and ORP8 are also localized to ER-mitochondria contacts and interact with the outer mitochondrial membrane protein PTPIP51. A functional lipid transfer (ORD) domain was required for this localization. Interestingly, ORP5 and ORP8 depletion leads to defects in mitochondria morphology and respiratory function. © 2016 The Authors.

The RNA recognition motif domains of RBM5 are required for RNA binding and cancer cell proliferation inhibition

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

Zhang, Lei; Zhang, Qing; Yang, Yu

Highlights: • RNA recognition motif domains of RBM5 are essential for cell proliferation inhibition. • RNA recognition motif domains of RBM5 are essential for apoptosis induction. • RNA recognition motif domains of RBM5 are essential for RNA binding. • RNA recognition motif domains of RBM5 are essential for caspase-2 alternative splicing. - Abstract: RBM5 is a known putative tumor suppressor gene that has been shown to function in cell growth inhibition by modulating apoptosis. RBM5 also plays a critical role in alternative splicing as an RNA binding protein. However, it is still unclear which domains of RBM5 are required formore » RNA binding and related functional activities. We hypothesized the two putative RNA recognition motif (RRM) domains of RBM5 spanning from amino acids 98–178 and 231–315 are essential for RBM5-mediated cell growth inhibition, apoptosis regulation, and RNA binding. To investigate this hypothesis, we evaluated the activities of the wide-type and mutant RBM5 gene transfer in low-RBM5 expressing A549 cells. We found that, unlike wild-type RBM5 (RBM5-wt), a RBM5 mutant lacking the two RRM domains (RBM5-ΔRRM), is unable to bind RNA, has compromised caspase-2 alternative splicing activity, lacks cell proliferation inhibition and apoptosis induction function in A549 cells. These data provide direct evidence that the two RRM domains of RBM5 are required for RNA binding and the RNA binding activity of RBM5 contributes to its function on apoptosis induction and cell growth inhibition.« less

Proton transfer and protein quake in photoreceptor activation

NASA Astrophysics Data System (ADS)

Xie, Aihua

2002-03-01

Proteins are able to perform an enormous variety of functions, while using only a limited number of underlying processes. One of these is proton transfer, found in a range of receptors and enzymes. It is conceivable that proton transfer is essential in biological energy transduction, but it is less evident how proton transfer is employed in receptor activation during biological signal transduction. An important question regarding receptor activation is how a localized event of detecting a stimulus at the active site drives global conformational changes involving protein surface for signal relay. We will present structural, kinetic and energetic studies on the activation mechanism of a prototype PAS domain photoreceptor, photoactive yellow protein (PYP). Our data reveal that the putative signaling state of PYP upon absorption of a blue photon is formed during a large-amplitude protein quake triggered by the formation of a new buried charge in a hydrophobic pocket at the active site of PYP via intramolecular proton transfer. This mechanism for protein quakes driven by proton transfer and electrostatic interactions may play roles during the functioning of other receptor proteins and non-receptor proteins that require large conformational changes.

Study of the individual cytochrome b5 and cytochrome b5 reductase domains of Ncb5or reveals a unique heme pocket and a possible role of the CS domain.

PubMed

Deng, Bin; Parthasarathy, Sudharsan; Wang, WenFang; Gibney, Brian R; Battaile, Kevin P; Lovell, Scott; Benson, David R; Zhu, Hao

2010-09-24

NADH cytochrome b(5) oxidoreductase (Ncb5or) is found in animals and contains three domains similar to cytochrome b(5) (b(5)), CHORD-SGT1 (CS), and cytochrome b(5) reductase (b(5)R). Ncb5or has an important function, as suggested by the diabetes and lipoatrophy phenotypes in Ncb5or null mice. To elucidate the structural and functional properties of human Ncb5or, we generated its individual b(5) and b(5)R domains (Ncb5or-b(5) and Ncb5or-b(5)R, respectively) and compared them with human microsomal b(5) (Cyb5A) and b(5)R (Cyb5R3). A 1.25 Å x-ray crystal structure of Ncb5or-b(5) reveals nearly orthogonal planes of the imidazolyl rings of heme-ligating residues His(89) and His(112), consistent with a highly anisotropic low spin EPR spectrum. Ncb5or is the first member of the cytochrome b(5) family shown to have such a heme environment. Like other b(5) family members, Ncb5or-b(5) has two helix-loop-helix motifs surrounding heme. However, Ncb5or-b(5) differs from Cyb5A with respect to location of the second heme ligand (His(112)) and of polypeptide conformation in its vicinity. Electron transfer from Ncb5or-b(5)R to Ncb5or-b(5) is much less efficient than from Cyb5R3 to Cyb5A, possibly as a consequence of weaker electrostatic interactions. The CS linkage probably obviates the need for strong interactions between b(5) and b(5)R domains in Ncb5or. Studies with a construct combining the Ncb5or CS and b(5)R domains suggest that the CS domain facilitates docking of the b(5) and b(5)R domains. Trp(114) is an invariant surface residue in all known Ncb5or orthologs but appears not to contribute to electron transfer from the b(5)R domain to the b(5) domain.

Evolution of the ferric reductase domain (FRD) superfamily: modularity, functional diversification, and signature motifs.

PubMed

Zhang, Xuezhi; Krause, Karl-Heinz; Xenarios, Ioannis; Soldati, Thierry; Boeckmann, Brigitte

2013-01-01

A heme-containing transmembrane ferric reductase domain (FRD) is found in bacterial and eukaryotic protein families, including ferric reductases (FRE), and NADPH oxidases (NOX). The aim of this study was to understand the phylogeny of the FRD superfamily. Bacteria contain FRD proteins consisting only of the ferric reductase domain, such as YedZ and short bFRE proteins. Full length FRE and NOX enzymes are mostly found in eukaryotic cells and all possess a dehydrogenase domain, allowing them to catalyze electron transfer from cytosolic NADPH to extracellular metal ions (FRE) or oxygen (NOX). Metazoa possess YedZ-related STEAP proteins, possibly derived from bacteria through horizontal gene transfer. Phylogenetic analyses suggests that FRE enzymes appeared early in evolution, followed by a transition towards EF-hand containing NOX enzymes (NOX5- and DUOX-like). An ancestral gene of the NOX(1-4) family probably lost the EF-hands and new regulatory mechanisms of increasing complexity evolved in this clade. Two signature motifs were identified: NOX enzymes are distinguished from FRE enzymes through a four amino acid motif spanning from transmembrane domain 3 (TM3) to TM4, and YedZ/STEAP proteins are identified by the replacement of the first canonical heme-spanning histidine by a highly conserved arginine. The FRD superfamily most likely originated in bacteria.

Impact of kinetic mass transfer on free convection in a porous medium

NASA Astrophysics Data System (ADS)

Lu, Chunhui; Shi, Liangsheng; Chen, Yiming; Xie, Yueqing; Simmons, Craig T.

2016-05-01

We investigate kinetic mass transfer effects on unstable density-driven flow and transport processes by numerical simulations of a modified Elder problem. The first-order dual-domain mass transfer model coupled with a variable-density-flow model is employed to describe transport behavior in porous media. Results show that in comparison to the no-mass-transfer case, a higher degree of instability and more unstable system is developed in the mass transfer case due to the reduced effective porosity and correspondingly a larger Rayleigh number (assuming permeability is independent on the mobile porosity). Given a constant total porosity, the magnitude of capacity ratio (i.e., immobile porosity/mobile porosity) controls the macroscopic plume profile in the mobile domain, while the magnitude of mass transfer timescale (i.e., the reciprocal of the mass transfer rate coefficient) dominates its evolution rate. The magnitude of capacity ratio plays an important role on the mechanism driving the mass flux into the aquifer system. Specifically, for a small capacity ratio, solute loading is dominated by the density-driven transport, while with increasing capacity ratio local mass transfer dominated solute loading may occur at later times. At significantly large times, however, both mechanisms contribute comparably to solute loading. Sherwood Number could be a nonmonotonic function of mass transfer timescale due to complicated interactions of solute between source zone, mobile zone and immobile zone in the top boundary layer, resulting in accordingly a similar behavior of the total mass. The initial assessment provides important insights into unstable density-driven flow and transport in the presence of kinetic mass transfer.

Sentiment classification technology based on Markov logic networks

NASA Astrophysics Data System (ADS)

He, Hui; Li, Zhigang; Yao, Chongchong; Zhang, Weizhe

2016-07-01

With diverse online media emerging, there is a growing concern of sentiment classification problem. At present, text sentiment classification mainly utilizes supervised machine learning methods, which feature certain domain dependency. On the basis of Markov logic networks (MLNs), this study proposed a cross-domain multi-task text sentiment classification method rooted in transfer learning. Through many-to-one knowledge transfer, labeled text sentiment classification, knowledge was successfully transferred into other domains, and the precision of the sentiment classification analysis in the text tendency domain was improved. The experimental results revealed the following: (1) the model based on a MLN demonstrated higher precision than the single individual learning plan model. (2) Multi-task transfer learning based on Markov logical networks could acquire more knowledge than self-domain learning. The cross-domain text sentiment classification model could significantly improve the precision and efficiency of text sentiment classification.

Optimal and robust control of quantum state transfer by shaping the spectral phase of ultrafast laser pulses.

PubMed

Guo, Yu; Dong, Daoyi; Shu, Chuan-Cun

2018-04-04

Achieving fast and efficient quantum state transfer is a fundamental task in physics, chemistry and quantum information science. However, the successful implementation of the perfect quantum state transfer also requires robustness under practically inevitable perturbative defects. Here, we demonstrate how an optimal and robust quantum state transfer can be achieved by shaping the spectral phase of an ultrafast laser pulse in the framework of frequency domain quantum optimal control theory. Our numerical simulations of the single dibenzoterrylene molecule as well as in atomic rubidium show that optimal and robust quantum state transfer via spectral phase modulated laser pulses can be achieved by incorporating a filtering function of the frequency into the optimization algorithm, which in turn has potential applications for ultrafast robust control of photochemical reactions.

Magnetic hydrogels from alkyne/cobalt carbonyl-functionalized ABA triblock copolymers

DOE PAGES

Jiang, Bingyin; Hom, Wendy L.; Chen, Xianyin; ...

2016-03-09

A series of alkyne-functionalized poly(4-(phenylethynyl)styrene)- block-poly(ethylene oxide)- block-poly(4-(phenylethynyl)styrene) (PPES-b-PEO-b-PPES) ABA triblock copolymers was synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization. PES n[Co 2(CO) 6] x-EO 800-PES n[Co 2(CO) 6] x ABA triblock copolymer/cobalt adducts (10–67 wt % PEO) were subsequently prepared by reaction of the alkyne-functionalized PPES block with Co 2(CO) 8 and their phase behavior was studied by TEM. Heating triblock copolymer/cobalt carbonyl adducts at 120 °C led to cross-linking of the PPES/Co domains and the formation of magnetic cobalt nanoparticles within the PPES/Co domains. Magnetic hydrogels could be prepared by swelling the PEO domains of the cross-linkedmore » materials with water. Furthermore, swelling tests, rheological studies and actuation tests demonstrated that the water capacity and modulus of the hydrogels were dependent upon the composition of the block copolymer precursors.« less

Hot-electron transfer in quantum-dot heterojunction films.

PubMed

Grimaldi, Gianluca; Crisp, Ryan W; Ten Brinck, Stephanie; Zapata, Felipe; van Ouwendorp, Michiko; Renaud, Nicolas; Kirkwood, Nicholas; Evers, Wiel H; Kinge, Sachin; Infante, Ivan; Siebbeles, Laurens D A; Houtepen, Arjan J

2018-06-13

Thermalization losses limit the photon-to-power conversion of solar cells at the high-energy side of the solar spectrum, as electrons quickly lose their energy relaxing to the band edge. Hot-electron transfer could reduce these losses. Here, we demonstrate fast and efficient hot-electron transfer between lead selenide and cadmium selenide quantum dots assembled in a quantum-dot heterojunction solid. In this system, the energy structure of the absorber material and of the electron extracting material can be easily tuned via a variation of quantum-dot size, allowing us to tailor the energetics of the transfer process for device applications. The efficiency of the transfer process increases with excitation energy as a result of the more favorable competition between hot-electron transfer and electron cooling. The experimental picture is supported by time-domain density functional theory calculations, showing that electron density is transferred from lead selenide to cadmium selenide quantum dots on the sub-picosecond timescale.

Analysis of Tomato spotted wilt virus NSs protein indicates the importance of the N-terminal domain for avirulence and RNA silencing suppression.

PubMed

de Ronde, Dryas; Pasquier, Adrien; Ying, Su; Butterbach, Patrick; Lohuis, Dick; Kormelink, Richard

2014-02-01

Recently, Tomato spotted wilt virus (TSWV) nonstructural protein NSs has been identified unambiguously as an avirulence (Avr) determinant for Tomato spotted wilt (Tsw)-based resistance. The observation that NSs from two natural resistance-breaking isolates had lost RNA silencing suppressor (RSS) activity and Avr suggested a link between the two functions. To test this, a large set of NSs mutants was generated by alanine substitutions in NSs from resistance-inducing wild-type strains (NSs(RI) ), amino acid reversions in NSs from resistance-breaking strains (NSs(RB)), domain deletions and swapping. Testing these mutants for their ability to suppress green fluorescent protein (GFP) silencing and to trigger a Tsw-mediated hypersensitive response (HR) revealed that the two functions can be separated. Changes in the N-terminal domain were found to be detrimental for both activities and indicated the importance of this domain, additionally supported by domain swapping between NSs(RI) and NSs(RB). Swapping domains between the closely related Tospovirus Groundnut ringspot virus (GRSV) NSs and TSWV NSs(RI) showed that Avr functionality could not simply be transferred between species. Although deletion of the C-terminal domain rendered NSs completely dysfunctional, only a few single-amino-acid mutations in the C-terminus affected both functions. Mutation of a GW/WG motif (position 17/18) rendered NSs completely dysfunctional for RSS and Avr activity, and indicated a putative interaction between NSs and Argonaute 1 (AGO1), and its importance in TSWV virulence and viral counter defence against RNA interference. © 2013 BSPP AND JOHN WILEY & SONS LTD.

Applied Routh approximation

NASA Technical Reports Server (NTRS)

Merrill, W. C.

1978-01-01

The Routh approximation technique for reducing the complexity of system models was applied in the frequency domain to a 16th order, state variable model of the F100 engine and to a 43d order, transfer function model of a launch vehicle boost pump pressure regulator. The results motivate extending the frequency domain formulation of the Routh method to the time domain in order to handle the state variable formulation directly. The time domain formulation was derived and a characterization that specifies all possible Routh similarity transformations was given. The characterization was computed by solving two eigenvalue-eigenvector problems. The application of the time domain Routh technique to the state variable engine model is described, and some results are given. Additional computational problems are discussed, including an optimization procedure that can improve the approximation accuracy by taking advantage of the transformation characterization.

Structural insights into FRS2α PTB domain recognition by neurotrophin receptor TrkB.

PubMed

Zeng, Lei; Kuti, Miklos; Mujtaba, Shiraz; Zhou, Ming-Ming

2014-07-01

The fibroblast growth factor receptor (FGFR) substrate 2 (FRS2) family proteins function as scaffolding adapters for receptor tyrosine kinases (RTKs). The FRS2α proteins interact with RTKs through the phosphotyrosine-binding (PTB) domain and transfer signals from the activated receptors to downstream effector proteins. Here, we report the nuclear magnetic resonance structure of the FRS2α PTB domain bound to phosphorylated TrkB. The structure reveals that the FRS2α-PTB domain is comprised of two distinct but adjacent pockets for its mutually exclusive interaction with either nonphosphorylated juxtamembrane region of the FGFR, or tyrosine phosphorylated peptides TrkA and TrkB. The new structural insights suggest rational design of selective small molecules through targeting of the two conjunct pockets in the FRS2α PTB domain. © 2014 Wiley Periodicals, Inc.

Conformational Changes of NADPH-Cytochrome P450 Oxidoreductase Are Essential for Catalysis and Cofactor Binding*

PubMed Central

Xia, Chuanwu; Hamdane, Djemel; Shen, Anna L.; Choi, Vivian; Kasper, Charles B.; Pearl, Naw May; Zhang, Haoming; Im, Sang-Choul; Waskell, Lucy; Kim, Jung-Ja P.

2011-01-01

The crystal structure of NADPH-cytochrome P450 reductase (CYPOR) implies that a large domain movement is essential for electron transfer from NADPH via FAD and FMN to its redox partners. To test this hypothesis, a disulfide bond was engineered between residues Asp147 and Arg514 in the FMN and FAD domains, respectively. The cross-linked form of this mutant protein, designated 147CC514, exhibited a significant decrease in the rate of interflavin electron transfer and large (≥90%) decreases in rates of electron transfer to its redox partners, cytochrome c and cytochrome P450 2B4. Reduction of the disulfide bond restored the ability of the mutant to reduce its redox partners, demonstrating that a conformational change is essential for CYPOR function. The crystal structures of the mutant without and with NADP+ revealed that the two flavin domains are joined by a disulfide linkage and that the relative orientations of the two flavin rings are twisted ∼20° compared with the wild type, decreasing the surface contact area between the two flavin rings. Comparison of the structures without and with NADP+ shows movement of the Gly631–Asn635 loop. In the NADP+-free structure, the loop adopts a conformation that sterically hinders NADP(H) binding. The structure with NADP+ shows movement of the Gly631–Asn635 loop to a position that permits NADP(H) binding. Furthermore, comparison of these mutant and wild type structures strongly suggests that the Gly631–Asn635 loop movement controls NADPH binding and NADP+ release; this loop movement in turn facilitates the flavin domain movement, allowing electron transfer from FMN to the CYPOR redox partners. PMID:21345800

Elucidating nitric oxide synthase domain interactions by molecular dynamics.

PubMed

Hollingsworth, Scott A; Holden, Jeffrey K; Li, Huiying; Poulos, Thomas L

2016-02-01

Nitric oxide synthase (NOS) is a multidomain enzyme that catalyzes the production of nitric oxide (NO) by oxidizing L-Arg to NO and L-citrulline. NO production requires multiple interdomain electron transfer steps between the flavin mononucleotide (FMN) and heme domain. Specifically, NADPH-derived electrons are transferred to the heme-containing oxygenase domain via the flavin adenine dinucleotide (FAD) and FMN containing reductase domains. While crystal structures are available for both the reductase and oxygenase domains of NOS, to date there is no atomic level structural information on domain interactions required for the final FMN-to-heme electron transfer step. Here, we evaluate a model of this final electron transfer step for the heme-FMN-calmodulin NOS complex based on the recent biophysical studies using a 105-ns molecular dynamics trajectory. The resulting equilibrated complex structure is very stable and provides a detailed prediction of interdomain contacts required for stabilizing the NOS output state. The resulting equilibrated complex model agrees well with previous experimental work and provides a detailed working model of the final NOS electron transfer step required for NO biosynthesis. © 2015 The Protein Society.

Structure and Function of the Catalytic Domain of the Dihydrolipoyl Acetyltransferase Component in Escherichia coli Pyruvate Dehydrogenase Complex*

PubMed Central

Wang, Junjie; Nemeria, Natalia S.; Chandrasekhar, Krishnamoorthy; Kumaran, Sowmini; Arjunan, Palaniappa; Reynolds, Shelley; Calero, Guillermo; Brukh, Roman; Kakalis, Lazaros; Furey, William; Jordan, Frank

2014-01-01

The Escherichia coli pyruvate dehydrogenase complex (PDHc) catalyzing conversion of pyruvate to acetyl-CoA comprises three components: E1p, E2p, and E3. The E2p is the five-domain core component, consisting of three tandem lipoyl domains (LDs), a peripheral subunit binding domain (PSBD), and a catalytic domain (E2pCD). Herein are reported the following. 1) The x-ray structure of E2pCD revealed both intra- and intertrimer interactions, similar to those reported for other E2pCDs. 2) Reconstitution of recombinant LD and E2pCD with E1p and E3p into PDHc could maintain at least 6.4% activity (NADH production), confirming the functional competence of the E2pCD and active center coupling among E1p, LD, E2pCD, and E3 even in the absence of PSBD and of a covalent link between domains within E2p. 3) Direct acetyl transfer between LD and coenzyme A catalyzed by E2pCD was observed with a rate constant of 199 s−1, comparable with the rate of NADH production in the PDHc reaction. Hence, neither reductive acetylation of E2p nor acetyl transfer within E2p is rate-limiting. 4) An unprecedented finding is that although no interaction could be detected between E1p and E2pCD by itself, a domain-induced interaction was identified on E1p active centers upon assembly with E2p and C-terminally truncated E2p proteins by hydrogen/deuterium exchange mass spectrometry. The inclusion of each additional domain of E2p strengthened the interaction with E1p, and the interaction was strongest with intact E2p. E2p domain-induced changes at the E1p active site were also manifested by the appearance of a circular dichroism band characteristic of the canonical 4′-aminopyrimidine tautomer of bound thiamin diphosphate (AP). PMID:24742683

Structure and function of the catalytic domain of the dihydrolipoyl acetyltransferase component in Escherichia coli pyruvate dehydrogenase complex.

PubMed

Wang, Junjie; Nemeria, Natalia S; Chandrasekhar, Krishnamoorthy; Kumaran, Sowmini; Arjunan, Palaniappa; Reynolds, Shelley; Calero, Guillermo; Brukh, Roman; Kakalis, Lazaros; Furey, William; Jordan, Frank

2014-05-30

The Escherichia coli pyruvate dehydrogenase complex (PDHc) catalyzing conversion of pyruvate to acetyl-CoA comprises three components: E1p, E2p, and E3. The E2p is the five-domain core component, consisting of three tandem lipoyl domains (LDs), a peripheral subunit binding domain (PSBD), and a catalytic domain (E2pCD). Herein are reported the following. 1) The x-ray structure of E2pCD revealed both intra- and intertrimer interactions, similar to those reported for other E2pCDs. 2) Reconstitution of recombinant LD and E2pCD with E1p and E3p into PDHc could maintain at least 6.4% activity (NADH production), confirming the functional competence of the E2pCD and active center coupling among E1p, LD, E2pCD, and E3 even in the absence of PSBD and of a covalent link between domains within E2p. 3) Direct acetyl transfer between LD and coenzyme A catalyzed by E2pCD was observed with a rate constant of 199 s(-1), comparable with the rate of NADH production in the PDHc reaction. Hence, neither reductive acetylation of E2p nor acetyl transfer within E2p is rate-limiting. 4) An unprecedented finding is that although no interaction could be detected between E1p and E2pCD by itself, a domain-induced interaction was identified on E1p active centers upon assembly with E2p and C-terminally truncated E2p proteins by hydrogen/deuterium exchange mass spectrometry. The inclusion of each additional domain of E2p strengthened the interaction with E1p, and the interaction was strongest with intact E2p. E2p domain-induced changes at the E1p active site were also manifested by the appearance of a circular dichroism band characteristic of the canonical 4'-aminopyrimidine tautomer of bound thiamin diphosphate (AP). © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Structure-guided Mutational Analysis of the Nucleotidyltransferase Domain of Escherichia coli DNA Ligase (LigA).

PubMed

Wang, Li Kai; Zhu, Hui; Shuman, Stewart

2009-03-27

NAD(+)-dependent DNA ligases (LigA) are ubiquitous in bacteria, where they are essential for growth and present attractive targets for antimicrobial drug discovery. LigA has a distinctive modular structure in which a nucleotidyltransferase catalytic domain is flanked by an upstream NMN-binding module and by downstream OB-fold, zinc finger, helix-hairpin-helix, and BRCT domains. Here we conducted a structure-function analysis of the nucleotidyltransferase domain of Escherichia coli LigA, guided by the crystal structure of the LigA-DNA-adenylate intermediate. We tested the effects of 29 alanine and conservative mutations at 15 amino acids on ligase activity in vitro and in vivo. We thereby identified essential functional groups that coordinate the reactive phosphates (Arg(136)), contact the AMP adenine (Lys(290)), engage the phosphodiester backbone flanking the nick (Arg(218), Arg(308), Arg(97) plus Arg(101)), or stabilize the active domain fold (Arg(171)). Finer analysis of the mutational effects revealed step-specific functions for Arg(136), which is essential for the reaction of LigA with NAD(+) to form the covalent ligase-AMP intermediate (step 1) and for the transfer of AMP to the nick 5'-PO(4) to form the DNA-adenylate intermediate (step 2) but is dispensable for phosphodiester formation at a preadenylylated nick (step 3).

The Cost of Concreteness: The Effect of Nonessential Information on Analogical Transfer

ERIC Educational Resources Information Center

Kaminski, Jennifer A.; Sloutsky, Vladimir M.; Heckler, Andrew F.

2013-01-01

Most theories of analogical transfer focus on similarities between the learning and transfer domains, where transfer is more likely between domains that share common surface features, similar elements, or common interpretations of structure. We suggest that characteristics of the learning instantiation alone can give rise to different levels of…

Numerical simulation of water evaporation inside vertical circular tubes

NASA Astrophysics Data System (ADS)

Ocłoń, Paweł; Nowak, Marzena; Majewski, Karol

2013-10-01

In this paper the results of simplified numerical analysis of water evaporation in vertical circular tubes are presented. The heat transfer in fluid domain (water or wet steam) and solid domain (tube wall) is analyzed. For the fluid domain the temperature field is calculated solving energy equation using the Control Volume Method and for the solid domain using the Finite Element Method. The heat transfer between fluid and solid domains is conjugated using the value of heat transfer coefficient from evaporating liquid to the tube wall. It is determined using the analytical Steiner-Taborek correlation. The pressure changes in fluid are computed using Friedel model.

a Comparison of Two Strategies for Avoiding Negative Transfer in Domain Adaptation Based on Logistic Regression

NASA Astrophysics Data System (ADS)

Paul, A.; Vogt, K.; Rottensteiner, F.; Ostermann, J.; Heipke, C.

2018-05-01

In this paper we deal with the problem of measuring the similarity between training and tests datasets in the context of transfer learning (TL) for image classification. TL tries to transfer knowledge from a source domain, where labelled training samples are abundant but the data may follow a different distribution, to a target domain, where labelled training samples are scarce or even unavailable, assuming that the domains are related. Thus, the requirements w.r.t. the availability of labelled training samples in the target domain are reduced. In particular, if no labelled target data are available, it is inherently difficult to find a robust measure of relatedness between the source and target domains. This is of crucial importance for the performance of TL, because the knowledge transfer between unrelated data may lead to negative transfer, i.e. to a decrease of classification performance after transfer. We address the problem of measuring the relatedness between source and target datasets and investigate three different strategies to predict and, consequently, to avoid negative transfer in this paper. The first strategy is based on circular validation. The second strategy relies on the Maximum Mean Discrepancy (MMD) similarity metric, whereas the third one is an extension of MMD which incorporates the knowledge about the class labels in the source domain. Our method is evaluated using two different benchmark datasets. The experiments highlight the strengths and weaknesses of the investigated methods. We also show that it is possible to reduce the amount of negative transfer using these strategies for a TL method and to generate a consistent performance improvement over the whole dataset.

Use of restrained molecular dynamics to predict the conformations of phosphorylated receiver domains in two-component signaling systems.

PubMed

Foster, Clay A; West, Ann H

2017-01-01

Two-component signaling (TCS) is the primary means by which bacteria, as well as certain plants and fungi, respond to external stimuli. Signal transduction involves stimulus-dependent autophosphorylation of a sensor histidine kinase and phosphoryl transfer to the receiver domain of a downstream response regulator. Phosphorylation acts as an allosteric switch, inducing structural and functional changes in the pathway's components. Due to their transient nature, phosphorylated receiver domains are challenging to characterize structurally. In this work, we provide a methodology for simulating receiver domain phosphorylation to predict conformations that are nearly identical to experimental structures. Using restrained molecular dynamics, phosphorylated conformations of receiver domains can be reliably sampled on nanosecond timescales. These simulations also provide data on conformational dynamics that can be used to identify regions of functional significance related to phosphorylation. We first validated this approach on several well-characterized receiver domains and then used it to compare the upstream and downstream components of the fungal Sln1 phosphorelay. Our results demonstrate that this technique provides structural insight, obtained in the absence of crystallographic or NMR information, regarding phosphorylation-induced conformational changes in receiver domains that regulate the output of their associated signaling pathway. To our knowledge, this is the first time such a protocol has been described that can be broadly applied to TCS proteins for predictive purposes. Proteins 2016; 85:155-176. © 2016 Wiley Periodicals, Inc. © 2016 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.

Experimental development of a Nusselt correlation for forced reciprocating oscillated vertical annular glycerol flow through a porous domain

NASA Astrophysics Data System (ADS)

Sayar, Ersin

2017-07-01

The objective of this paper is to investigate the heat transfer to oscillating annular flow of a viscous fluid. The flow media includes stationary stainless steel wool porous domain and glycerol as the working fluid. The effects of actuation frequency and wall heat flux on the temperature field and resultant heat convection coefficient are studied. The temperature values at radial direction are close each other as porous media mixes the glycerol successfully. A correlation with a functional dependence to kinetic Reynolds number is recommended that can be used to acquire the averaged heat transfer for oscillating flows. Present experimental results with glycerol in a porous media are compared to the published experimental works with water. For the limited case of the two working fluids, Nusselt number is normalized well using the Prandtl number (Pr0.67). Results are also compared to non-porous media study and heat transfer is found to increase up to a factor of five in porous media. The recommended correlation is claimed to have a significant role for anticipating heat transfer of oscillating viscous fluid not only at low frequencies but also at low heat fluxes in a porous and permeable solid media.

Dynamic analysis of patterns of renal sympathetic nerve activity: implications for renal function.

PubMed

DiBona, Gerald F

2005-03-01

Methods of dynamic analysis are used to provide additional understanding of the renal sympathetic neural control of renal function. The concept of functionally specific subgroups of renal sympathetic nerve fibres conveying information encoded in the frequency domain is presented. Analog pulse modulation and pseudorandom binary sequence stimulation patterns are used for the determination of renal vascular frequency response. Transfer function analysis is used to determine the effects of non-renal vasoconstrictor and vasoconstrictor intensities of renal sympathetic nerve activity on dynamic autoregulation of renal blood flow.

Real-Time Parameter Estimation Method Applied to a MIMO Process and its Comparison with an Offline Identification Method

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

Kaplanoglu, Erkan; Safak, Koray K.; Varol, H. Selcuk

2009-01-12

An experiment based method is proposed for parameter estimation of a class of linear multivariable systems. The method was applied to a pressure-level control process. Experimental time domain input/output data was utilized in a gray-box modeling approach. Prior knowledge of the form of the system transfer function matrix elements is assumed to be known. Continuous-time system transfer function matrix parameters were estimated in real-time by the least-squares method. Simulation results of experimentally determined system transfer function matrix compare very well with the experimental results. For comparison and as an alternative to the proposed real-time estimation method, we also implemented anmore » offline identification method using artificial neural networks and obtained fairly good results. The proposed methods can be implemented conveniently on a desktop PC equipped with a data acquisition board for parameter estimation of moderately complex linear multivariable systems.« less

A direct approach to the design of linear multivariable systems

NASA Technical Reports Server (NTRS)

Agrawal, B. L.

1974-01-01

Design of multivariable systems is considered and design procedures are formulated in the light of the most recent work on model matching. The word model matching is used exclusively to mean matching the input-output behavior of two systems. The term is used in the frequency domain to indicate the comparison of two transfer matrices containing transfer functions as elements. Design methods where non-interaction is not used as a criteria were studied. Two design methods are considered. The first method of design is based solely upon the specification of generalized error coefficients for each individual transfer function of the overall system transfer matrix. The second design method is called the pole fixing method because all the system poles are fixed at preassigned positions. The zeros of terms either above or below the diagonal are partially fixed via steady state error coefficients. The advantages and disadvantages of each method are discussed and an example is worked to demonstrate their uses. The special cases of triangular decoupling and minimum constraints are discussed.

Ab Initio Vibrational Levels For HO2 and Vibrational Splittings for Hydrogen Atom Transfer

NASA Technical Reports Server (NTRS)

Barclay, V. J.; Dateo, Christopher E.; Hamilton, I. P.; Arnold, James O. (Technical Monitor)

1994-01-01

We calculate vibrational levels and wave functions for HO2 using the recently reported ab initio potential energy surface of Walch and Duchovic. There is intramolecular hydrogen atom transfer when the hydrogen atom tunnels through a T-shaped saddle point separating two equivalent equilibrium geometries, and correspondingly, the energy levels are split. We focus on vibrational levels and wave functions with significant splitting. The first three vibrational levels with splitting greater than 2/cm are (15 0), (0 7 1) and (0 8 0) where V(sub 2) is the O-O-H bend quantum number. We discuss the dynamics of hydrogen atom transfer; in particular, the O-O distances at which hydrogen atom transfer is most probable for these vibrational levels. The material of the proposed presentation was reviewed and the technical content will not reveal any information not already in the public domain and will not give any foreign industry or government a competitive advantage.

FAST TRACK COMMUNICATION Critical exponents of domain walls in the two-dimensional Potts model

NASA Astrophysics Data System (ADS)

Dubail, Jérôme; Lykke Jacobsen, Jesper; Saleur, Hubert

2010-12-01

We address the geometrical critical behavior of the two-dimensional Q-state Potts model in terms of the spin clusters (i.e. connected domains where the spin takes a constant value). These clusters are different from the usual Fortuin-Kasteleyn clusters, and are separated by domain walls that can cross and branch. We develop a transfer matrix technique enabling the formulation and numerical study of spin clusters even when Q is not an integer. We further identify geometrically the crossing events which give rise to conformal correlation functions. This leads to an infinite series of fundamental critical exponents h_{\\ell _1-\\ell _2,2\\ell _1}, valid for 0 <= Q <= 4, that describe the insertion of ell1 thin and ell2 thick domain walls.

Origin of band bending at domain boundaries of MoS2: First-principles study

NASA Astrophysics Data System (ADS)

Kaneko, Tomoaki; Saito, Riichiro

2018-04-01

Using first-principles calculations based on density functional theory, the energetics and electronic structure of domain boundaries of MoS2, in which the same polar edges face each other, are investigated. We find that the interface model with homoelemental bonds is not energetically preferred in this system. The domain boundaries have defect levels that have wide distributions inside the band gap of MoS2. The upshift (or downshift) of the MoS2 energy band occurs around the domain boundaries when the occupation number of electrons in the defect levels increases (or decreases). The charge transfer of electrons from the graphite substrate plays an important role in band bending, which is observed in the recent experiments by scanning tunneling microscopy/spectroscopy.

Application of unsteady flow rate evaluations to identify the dynamic transfer function of a cavitatingVenturi

NASA Astrophysics Data System (ADS)

Marie-Magdeleine, A.; Fortes-Patella, R.; Lemoine, N.; Marchand, N.

2012-11-01

This study concerns the simulation of the implementation of the Kinetic Differential Pressure (KDP) method used for the unsteady mass flow rate evaluation in order to identify the dynamic transfer matrix of a cavitatingVenturi. Firstly, the equations of the IZ code used for this simulation are introduced. Next, the methodology for evaluating unsteady pressures and mass flow rates at the inlet and the outlet of the cavitatingVenturi and for identifying the dynamic transfer matrix is presented. Later, the robustness of the method towards measurement uncertainties implemented as a Gaussian white noise is studied. The results of the numerical simulations let us estimate the system linearity domain and to perform the Empirical Transfer Function Evaluation on the inlet frequency per frequency signal and on the chirp signal tests. Then the pressure data obtained with the KDP method is taken and the identification procedure by ETFE and by the user-made Auto-Recursive Moving-Average eXogenous algorithms is performed and the obtained transfer matrix coefficients are compared with those obtained from the simulated input and output data.

Impact Response Characteristics of Polymeric Materials

DTIC Science & Technology

1981-11-01

amplitude-frequency domain. In the language of signal communications an input signal given by some time dependence FAt) is introduced into a " channel ...fixed and not altered by the signal. The channel can be charac- terized by its own function H(t), called the transfer function. This concept can be...rcpresented schematically as follows: Input Signal - [ Channel ] -- Output Signal At) H(t) G(t) In our case the input signal is the impact event, the output

"Decisions, decisions, decisions": transfer and specificity of decision-making skill between sports.

PubMed

Causer, Joe; Ford, Paul R

2014-08-01

The concept of transfer of learning holds that previous practice or experience in one task or domain will enable successful performance in another related task or domain. In contrast, specificity of learning holds that previous practice or experience in one task or domain does not transfer to other related tasks or domains. The aim of the current study is to examine whether decision-making skill transfers between sports that share similar elements, or whether it is specific to a sport. Participants (n = 205) completed a video-based temporal occlusion decision-making test in which they were required to decide on which action to execute across a series of 4 versus 4 soccer game situations. A sport engagement questionnaire was used to identify 106 soccer players, 43 other invasion sport players and 58 other sport players. Positive transfer of decision-making skill occurred between soccer and other invasion sports, which are related and have similar elements, but not from volleyball, supporting the concept of transfer of learning.

Synthesis of feedback systems with large plant ignorance for prescribed time domain tolerances

NASA Technical Reports Server (NTRS)

Horowitz, I. M.; Sidi, M.

1971-01-01

There is given a minimum-phase plant transfer function, with prescribed bounds on its parameter values. The plant is imbedded in a two-degree-of freedom feedback system, which is to be designed such that the system time response to a deterministic input lies within specified boundaries. Subject to the above, the design should be such as to minimize the effect of sensor noise at the input to the plant. This report presents a design procedure for this purpose, based on frequency response concepts. The time-domain tolerances are translated into equivalent frequency response tolerances. The latter lead to bounds on the loop transmission function in the form of continuous curves on the Nichols chart. The properties of the loop transmission function which satisfy these bounds with minimum effect of sensor noise, are derived.

Femtosecond Time-Resolved Photoelectron Imaging of Excited Doped Helium Nanodroplets

NASA Astrophysics Data System (ADS)

Saladrigas, Catherine; Bacellar, Camila; Leone, Stephen R.; Neumark, Daniel M.; Gessner, Oliver

2017-04-01

Helium nanodroplets are excellent matrices for high resolution spectroscopy and the study of ultracold chemistry. They are optically transparent. In their electronic ground state, interact very weakly with any atomic or molecular dopant. Electronically excited droplets, however, can strongly interact with dopants through a variety of relaxation mechanisms. Previously, these host-dopant interactions were studied in the energy domain, revealing Penning ionization processes enabled by energy transfer between the droplet host and atomic dopants. Using femtosecond time resolved XUV photoelectron imaging, we plan to perform complementary experiments in the time domain to gain deeper insight into the timescales of energy transfer processes and how they compete with internal droplet relaxation. First experiments will be performed using noble gas dopants, such as Kr and Ne, which will be compared to previous energy-domain studies. Femtosecond XUV pulses produced by high harmonic generation will be used to excite the droplets, IR and near-UV light will be used to monitor the relaxation dynamics. Using velocity map imaging, both photoelectron kinetic energies and angular distributions will be recorded as a function of time. Preliminary results and proposed experiments will be presented.

Evolution of the Ferric Reductase Domain (FRD) Superfamily: Modularity, Functional Diversification, and Signature Motifs

PubMed Central

Zhang, Xuezhi; Krause, Karl-Heinz; Xenarios, Ioannis; Soldati, Thierry; Boeckmann, Brigitte

2013-01-01

A heme-containing transmembrane ferric reductase domain (FRD) is found in bacterial and eukaryotic protein families, including ferric reductases (FRE), and NADPH oxidases (NOX). The aim of this study was to understand the phylogeny of the FRD superfamily. Bacteria contain FRD proteins consisting only of the ferric reductase domain, such as YedZ and short bFRE proteins. Full length FRE and NOX enzymes are mostly found in eukaryotic cells and all possess a dehydrogenase domain, allowing them to catalyze electron transfer from cytosolic NADPH to extracellular metal ions (FRE) or oxygen (NOX). Metazoa possess YedZ-related STEAP proteins, possibly derived from bacteria through horizontal gene transfer. Phylogenetic analyses suggests that FRE enzymes appeared early in evolution, followed by a transition towards EF-hand containing NOX enzymes (NOX5- and DUOX-like). An ancestral gene of the NOX(1-4) family probably lost the EF-hands and new regulatory mechanisms of increasing complexity evolved in this clade. Two signature motifs were identified: NOX enzymes are distinguished from FRE enzymes through a four amino acid motif spanning from transmembrane domain 3 (TM3) to TM4, and YedZ/STEAP proteins are identified by the replacement of the first canonical heme-spanning histidine by a highly conserved arginine. The FRD superfamily most likely originated in bacteria. PMID:23505460

Transfer factor - hypotheses for its structure and function.

PubMed

Shifrine, M; Scibienski, R

1975-01-01

Transfer factor (TF) is a dialyzable extract from primed lymphocytes that is able to transfer specific delayed hypersensitivity from one animal to another. On the basis of available data we suggest that TF is a polypeptide with a molecular weight below 15,000 daltons. We hypothesize that TF is the variable light or heavy chain domain of immunoglobulin: such a molecule conforms with the accepted properties of TF and also has the necessary specificity requirements. We also hypothesize that TF is part of a receptor site. beta-2-microglobulin, a molecule that is an integral part of cell surfaces, could be the anchor for TF. beta-2-microglobulin has homologies with the constant portion of immunoglobulin light or heavy chain and thus would combine with the variable domain (TF) to form a complete receptor site for a specific antigen. The properties of TF suggest its mode of action, which is discussed in detail in the text. The biologic advantages of TF is its ability to confer immediate (immunologie specific) protection while the 'normal' immune response develops.

Significance of Thermal Fluvial Incision and Bedrock Transfer due to Ice Advection on Greenland Ice Sheet Topography

NASA Astrophysics Data System (ADS)

Crozier, J. A.; Karlstrom, L.; Yang, K.

2017-12-01

Ice sheet surface topography reflects a complicated combination of processes that act directly upon the surface and that are products of ice advection. Using recently-available high resolution ice velocity, imagery, ice surface elevation, and bedrock elevation data sets, we seek to determine the domain of significance of two important processes - thermal fluvial incision and transfer of bedrock topography through the ice sheet - on controlling surface topography in the ablation zone. Evaluating such controls is important for understanding how melting of the GIS surface during the melt season may be directly imprinted in topography through supraglacial drainage networks, and indirectly imprinted through its contribution to basal sliding that affects bedrock transfer. We use methods developed by (Karlstrom and Yang, 2016) to identify supraglacial stream networks on the GIS, and use high resolution surface digital elevation models as well as gridded ice velocity and melt rate models to quantify surface processes. We implement a numerically efficient Fourier domain bedrock transfer function (Gudmundsson, 2003) to predict surface topography due to ice advection over bedrock topography obtained from radar. Despite a number of simplifying assumptions, the bedrock transfer function predicts the observed ice sheet surface in most regions of the GIS with ˜90% accuracy, regardless of the presence or absence of supraglacial drainage networks. This supports the hypothesis that bedrock is the most significant driver of ice surface topography on wavelengths similar to ice thickness. Ice surface topographic asymmetry on the GIS is common, with slopes in the direction of ice flow steeper than those faced opposite to ice flow, consistent with bedrock transfer theory. At smaller wavelengths, topography consistent with fluvial erosion by surface hydrologic features is evident. We quantify the effect of ice advection versus fluvial thermal erosion on supraglacial longitudinal stream profiles, as a function of location on the GIS (hence ice thickness and background melt rate) using spectral techniques to quantify longitudinal stream profiles. This work should provide a predictive guide for which processes are responsible for ice sheet topography scales from several m (DEM resolution) up to several ice thicknesses.

Analogical transfer as guided by an abstraction process: the case of learning by doing in text editing.

PubMed

Sander, E; Richard, J F

1997-11-01

The authors proposed that not only are the first attempts to solve a problem made by analogy but also that progress in learning can be guided by referring to more abstract knowledge, which affords new possibilities. Two experiments investigated this view in a situation of learning how to use a text editor. Experiments 1A to 1C identified the knowledge associated with 3 domains hypothesized as sources of transfer at increasing levels of abstraction (typewriting, writing in general, manipulating objects). Experiment 2 tested whether participants first use their knowledge about typewriting, then about writing in general, and then about manipulating objects. The data showed that the order of acquisition of text editor functions appeared to be strongly related to this hierarchy, supporting the idea that part of learning consists of discovering properties of objects by accessing increasingly general domains.

Interplay between the spin transfer and spin orbit torques on domain walls at the 5d/3d-alloy interfaces

NASA Astrophysics Data System (ADS)

Kalitsov, Alan; Okatov, Sergey; Zarzhitsky, Pavel; Chshiev, Mairbek; Velev, Julian; Butler, William; Mryasov, Oleg

2014-03-01

The manipulations of domain wall (DW) in thin ferromagnetic layers by current and the spin-orbit coupling (SOC) have attracted significant interest. We report two band model calculations of the spin torque (ST) and the spin current (SC) at 5d/3d interfaces with head-to-head, Bloch and Neel DWs. These calculations are based on the non-equilibrium Green Function formalism and the tight binding Hamiltonian including the s-d exchange interactions and the Rashba SOC parameterized on the basis of ab-initio calculations for Fe/W, FeCo/Ta and Co/Pt interfaces. We find that SOC significantly modifies the ST and violates relations between the spin transfer torque and the divergence of the spin current. This work was supported in part by a Semiconductor Research Corporation program, sponsored by MARCO and DARPA.

Frequency-Domain Characterization of Optic Flow and Vision-Based Ocellar Sensing for Rotational Motion

DTIC Science & Technology

2017-04-01

complementary fusion: Fourth-order Butterworth filter was used to high -pass ocelli and low-pass optic flow. The normalized cutoff frequency had to be kept...information introduced by luminance change. The high - frequency cutoff was added to reject the flickering noise for indoor usage. The filtered signals from the...function of the low- pass filter is to attenuate high - frequency noise. The final band-pass filter transfer function is in Eq. 2. (()

Autonomous Inter-Task Transfer in Reinforcement Learning Domains

DTIC Science & Technology

2008-08-01

Twentieth International Joint Conference on Artificial Intelli - gence, 2007. 304 Fumihide Tanaka and Masayuki Yamamura. Multitask reinforcement learning...Functions . . . . . . . . . . . . . . . . . . . . . . 17 2.2.3 Artificial Neural Networks . . . . . . . . . . . . . . . . . . . . 18 2.2.4 Instance-based...tures [Laird et al., 1986, Choi et al., 2007]. However, TL for RL tasks has only recently been gaining attention in the artificial intelligence

Parametric Robust Control and System Identification: Unified Approach

NASA Technical Reports Server (NTRS)

Keel, L. H.

1996-01-01

During the period of this support, a new control system design and analysis method has been studied. This approach deals with control systems containing uncertainties that are represented in terms of its transfer function parameters. Such a representation of the control system is common and many physical parameter variations fall into this type of uncertainty. Techniques developed here are capable of providing nonconservative analysis of such control systems with parameter variations. We have also developed techniques to deal with control systems when their state space representations are given rather than transfer functions. In this case, the plant parameters will appear as entries of state space matrices. Finally, a system modeling technique to construct such systems from the raw input - output frequency domain data has been developed.

Function and horizontal transfer of the small terminase subunit of the tailed bacteriophage Sf6 DNA packaging nanomotor

PubMed Central

Leavitt, Justin C.; Gilcrease, Eddie B.; Wilson, Kassandra; Casjens, Sherwood R.

2013-01-01

Bacteriophage Sf6 DNA packaging series initiate at many locations across a 2 kbp region. Our in vivo studies that show that Sf6 small terminase subunit (TerS) protein recognizes a specific packaging (pac) site near the center of this region, that this site lies within the portion of the Sf6 gene that encodes the DNA-binding domain of TerS protein, that this domain of the TerS protein is responsible for the imprecision in Sf6 packaging initiation, and that the DNA-binding domain of TerS must be covalently attached to the domain that interacts with the rest of the packaging motor. The TerS DNA-binding domain is self-contained in that it apparently does not interact closely with the rest of the motor and it binds to a recognition site that lies within the DNA that encodes the domain. This arrangement has allowed the horizontal exchange of terS genes among phages to be very successful. PMID:23562538

Multiple scale dynamo

PubMed Central

Le Mouël, Jean-Louis; Allègre, Claude J.; Narteau, Clément

1997-01-01

A scaling law approach is used to simulate the dynamo process of the Earth’s core. The model is made of embedded turbulent domains of increasing dimensions, until the largest whose size is comparable with the site of the core, pervaded by large-scale magnetic fields. Left-handed or right-handed cyclones appear at the lowest scale, the scale of the elementary domains of the hierarchical model, and disappear. These elementary domains then behave like electromotor generators with opposite polarities depending on whether they contain a left-handed or a right-handed cyclone. To transfer the behavior of the elementary domains to larger ones, a dynamic renormalization approach is used. A simple rule is adopted to determine whether a domain of scale l is a generator—and what its polarity is—in function of the state of the (l − 1) domains it is made of. This mechanism is used as the main ingredient of a kinematic dynamo model, which displays polarity intervals, excursions, and reversals of the geomagnetic field. PMID:11038547

Mechanisms of polarized membrane trafficking in neurons – focusing in on endosomes

PubMed Central

Lasiecka, Zofia M.; Winckler, Bettina

2011-01-01

Neurons are polarized cells that have a complex and unique morphology: long processes (axons and dendrites) extending far from the cell body. In addition, the somatodendritic and axonal domains are further divided into specific subdomains, such as synapses (pre- and postsynaptic specializations), proximal and distal dendrites, axon initial segments, nodes of Ranvier, and axon growth cones. The striking asymmetry and complexity of neuronal cells is necessary for their function in receiving, processing and transferring electrical signals, with each domain playing a precise function in these processes. In order to establish and maintain distinct neuronal domains, mechanisms must exist for protein delivery to specific neuronal compartments, such that each compartment has the correct functional molecular composition. How polarized membrane domains are established and maintained is a long-standing question. Transmembrane proteins, such as receptors and adhesion molecules, can be transported to their proper membrane domains by several pathways. The biosynthetic secretory system delivers newly synthesized transmembrane proteins from the ER-Golgi via the trans-Golgi network (TGN) to the plasma membrane. In addition, the endosomal system is critically involved in many instances in ensuring proper (re)targeting of membrane components because it can internalize and degrade mislocalized proteins, or recycle proteins from one domain to another. The endosomal system is thus crucial for establishing and maintaining neuronal polarity. In this review, we focus mainly on the intracellular compartments that serve as sorting stations for polarized transport, with particular emphasis on the emerging roles of endosomes. PMID:21762782

Pulse analysis of acoustic emission signals. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Houghton, J. R.

1976-01-01

A method for the signature analysis of pulses in the frequency domain and the time domain is presented. Fourier spectrum, Fourier transfer function, shock spectrum and shock spectrum ratio are examined in the frequency domain analysis, and pulse shape deconvolution is developed for use in the time domain analysis. To demonstrate the relative sensitivity of each of the methods to small changes in the pulse shape, signatures of computer modeled systems with analytical pulses are presented. Optimization techniques are developed and used to indicate the best design parameters values for deconvolution of the pulse shape. Several experiments are presented that test the pulse signature analysis methods on different acoustic emission sources. These include acoustic emissions associated with: (1) crack propagation, (2) ball dropping on a plate, (3) spark discharge and (4) defective and good ball bearings.

Novel Mechanism of Hemin Capture by Hbp2, the Hemoglobin-binding Hemophore from Listeria monocytogenes*

PubMed Central

Malmirchegini, G. Reza; Sjodt, Megan; Shnitkind, Sergey; Sawaya, Michael R.; Rosinski, Justin; Newton, Salete M.; Klebba, Phillip E.; Clubb, Robert T.

2014-01-01

Iron is an essential nutrient that is required for the growth of the bacterial pathogen Listeria monocytogenes. In cell cultures, this microbe secretes hemin/hemoglobin-binding protein 2 (Hbp2; Lmo2185) protein, which has been proposed to function as a hemophore that scavenges heme from the environment. Based on its primary sequence, Hbp2 contains three NEAr transporter (NEAT) domains of unknown function. Here we show that each of these domains mediates high affinity binding to ferric heme (hemin) and that its N- and C-terminal domains interact with hemoglobin (Hb). The results of hemin transfer experiments are consistent with Hbp2 functioning as an Hb-binding hemophore that delivers hemin to other Hbp2 proteins that are attached to the cell wall. Surprisingly, our work reveals that the central NEAT domain in Hbp2 binds hemin even though its primary sequence lacks a highly conserved YXXXY motif that is used by all other previously characterized NEAT domains to coordinate iron in the hemin molecule. To elucidate the mechanism of hemin binding by Hbp2, we determined crystal structures of its central NEAT domain (Hbp2N2; residues 183–303) in its free and hemin-bound states. The structures reveal an unprecedented mechanism of hemin binding in which Hbp2N2 undergoes a major conformational rearrangement that facilitates metal coordination by a non-canonical tyrosine residue. These studies highlight previously unrecognized plasticity in the hemin binding mechanism of NEAT domains and provide insight into how L. monocytogenes captures heme iron. PMID:25315777

UXDs-Driven Transferring Method from TRIZ Solution to Domain Solution

NASA Astrophysics Data System (ADS)

Ma, Lihui; Cao, Guozhong; Chang, Yunxia; Wei, Zihui; Ma, Kai

The translation process from TRIZ solutions to domain solutions is an analogy-based process. TRIZ solutions, such as 40 inventive principles and the related cases, are medium-solutions for domain problems. Unexpected discoveries (UXDs) are the key factors to trigger designers to generate new ideas for domain solutions. The Algorithm of UXD resolving based on Means-Ends Analysis(MEA) is studied and an UXDs-driven transferring method from TRIZ solution to domain solution is formed. A case study shows the application of the process.

Transfer of Satellite Rainfall Uncertainty from Gauged to Ungauged Regions at Regional and Seasonal Timescales

NASA Technical Reports Server (NTRS)

Tang, Ling; Hossain, Faisal; Huffman, George J.

2010-01-01

Hydrologists and other users need to know the uncertainty of the satellite rainfall data sets across the range of time/space scales over the whole domain of the data set. Here, uncertainty' refers to the general concept of the deviation' of an estimate from the reference (or ground truth) where the deviation may be defined in multiple ways. This uncertainty information can provide insight to the user on the realistic limits of utility, such as hydrologic predictability, that can be achieved with these satellite rainfall data sets. However, satellite rainfall uncertainty estimation requires ground validation (GV) precipitation data. On the other hand, satellite data will be most useful over regions that lack GV data, for example developing countries. This paper addresses the open issues for developing an appropriate uncertainty transfer scheme that can routinely estimate various uncertainty metrics across the globe by leveraging a combination of spatially-dense GV data and temporally sparse surrogate (or proxy) GV data, such as the Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar and the Global Precipitation Measurement (GPM) mission Dual-Frequency Precipitation Radar. The TRMM Multi-satellite Precipitation Analysis (TMPA) products over the US spanning a record of 6 years are used as a representative example of satellite rainfall. It is shown that there exists a quantifiable spatial structure in the uncertainty of satellite data for spatial interpolation. Probabilistic analysis of sampling offered by the existing constellation of passive microwave sensors indicate that transfer of uncertainty for hydrologic applications may be effective at daily time scales or higher during the GPM era. Finally, a commonly used spatial interpolation technique (kriging), that leverages the spatial correlation of estimation uncertainty, is assessed at climatologic, seasonal, monthly and weekly timescales. It is found that the effectiveness of kriging is sensitive to the type of uncertainty metric, time scale of transfer and the density of GV data within the transfer domain. Transfer accuracy is lowest at weekly timescales with the error doubling from monthly to weekly.However, at very low GV data density (<20% of the domain), the transfer accuracy is too low to show any distinction as a function of the timescale of transfer.

Modulation and Functional Role of the Orientations of the N- and P-Domains of Cu+ -Transporting ATPase along the Ion Transport Cycle.

PubMed

Meng, Dan; Bruschweiler-Li, Lei; Zhang, Fengli; Brüschweiler, Rafael

2015-08-18

Ion transport of different P-type ATPases is regulated similarly through the interplay of multiple protein domains. In the presence of ATP, binding of a cation to the ion binding site in the transmembrane helices leads to the phosphorylation of the P-domain, allowing ion transfer across the membrane. The details of the mechanism, however, are not clear. Here, we report the modulation of the orientation between the N- and P-domains of Cu(+)-transporting ATPase along the ion transport cycle using high-resolution nuclear magnetic resonance spectroscopy in solution. On the basis of residual dipolar coupling measurements, it is found that the interdomain orientation (relative openness) of the N- and P-domains is distinctly modulated depending on the specific state of the N- and P-domains along the ion translocation cycle. The two domains' relative position in the apo state is semiopen, whereas it becomes closed upon binding of ATP to the N-domain. After phosphorylation of the P-domain and the release of ADP, the opening, however, becomes the widest among all the states. We reason such wide opening resulting from the departure of ADP prepares the N- and P-domains to accommodate the A-domain for interaction and, hence, promote ion transport and allow dephosphorylation of the P-domain. Such wide interdomain opening is abolished when an Asn to Asp mutation is introduced into the conserved DXXK motif located in the hinge region of the N- and P-domains of Cu(+)-ATPase, suggesting the indispensible role of the N- and P-interdomain orientation during ion transportation. Our results shed new light on the structural and mechanistic details of P-type ATPase function at large.

Terahertz quasi time-domain spectroscopy based on telecom technology for 1550 nm.

PubMed

Kohlhaas, Robert B; Rehn, Arno; Nellen, Simon; Koch, Martin; Schell, Martin; Dietz, Roman J B; Balzer, Jan C

2017-05-29

We present a fiber-coupled terahertz quasi time-domain spectroscopy system driven by a laser with a central wavelength of 1550 nm. By using a commercially available multimode laser diode in combination with state-of-the-art continuous wave antennas, a bandwidth of more than 1.8 THz is achieved. The peak signal-to-noise ratio is around 60 dB. A simulation based on the optical spectrum of the laser diode and the transfer function of the THz path is in agreement with the experimental results. The system is used to extract the refractive index from two different samples and the results indicate that the performance is up to 1.8 THz comparable to a terahertz time-domain spectroscopy system.

Rapid updating of optical arbitrary waveforms via time-domain multiplexing.

PubMed

Scott, R P; Fontaine, N K; Yang, C; Geisler, D J; Okamoto, K; Heritage, J P; Yoo, S J B

2008-05-15

We demonstrate high-fidelity optical arbitrary waveform generation with 5 GHz waveform switching via time-domain multiplexing. Compact, integrated waveform shapers based on silica arrayed-waveguide grating pairs with 10 GHz channel spacing are used to shape (line-by-line) two different waveforms from the output of a 10-mode x 10 GHz optical frequency comb generator. Characterization of the time multiplexer's complex transfer function (amplitude and phase) by frequency-resolved optical gating permits compensation of its impact on the switched waveforms and matching of the measured and target waveforms to better than G'=5%.

Missing Modality Transfer Learning via Latent Low-Rank Constraint.

PubMed

Ding, Zhengming; Shao, Ming; Fu, Yun

2015-11-01

Transfer learning is usually exploited to leverage previously well-learned source domain for evaluating the unknown target domain; however, it may fail if no target data are available in the training stage. This problem arises when the data are multi-modal. For example, the target domain is in one modality, while the source domain is in another. To overcome this, we first borrow an auxiliary database with complete modalities, then consider knowledge transfer across databases and across modalities within databases simultaneously in a unified framework. The contributions are threefold: 1) a latent factor is introduced to uncover the underlying structure of the missing modality from the known data; 2) transfer learning in two directions allows the data alignment between both modalities and databases, giving rise to a very promising recovery; and 3) an efficient solution with theoretical guarantees to the proposed latent low-rank transfer learning algorithm. Comprehensive experiments on multi-modal knowledge transfer with missing target modality verify that our method can successfully inherit knowledge from both auxiliary database and source modality, and therefore significantly improve the recognition performance even when test modality is inaccessible in the training stage.

A protein domain-centric approach for the comparative analysis of human and yeast phenotypically relevant mutations

PubMed Central

2013-01-01

Background The body of disease mutations with known phenotypic relevance continues to increase and is expected to do so even faster with the advent of new experimental techniques such as whole-genome sequencing coupled with disease association studies. However, genomic association studies are limited by the molecular complexity of the phenotype being studied and the population size needed to have adequate statistical power. One way to circumvent this problem, which is critical for the study of rare diseases, is to study the molecular patterns emerging from functional studies of existing disease mutations. Current gene-centric analyses to study mutations in coding regions are limited by their inability to account for the functional modularity of the protein. Previous studies of the functional patterns of known human disease mutations have shown a significant tendency to cluster at protein domain positions, namely position-based domain hotspots of disease mutations. However, the limited number of known disease mutations remains the main factor hindering the advancement of mutation studies at a functional level. In this paper, we address this problem by incorporating mutations known to be disruptive of phenotypes in other species. Focusing on two evolutionarily distant organisms, human and yeast, we describe the first inter-species analysis of mutations of phenotypic relevance at the protein domain level. Results The results of this analysis reveal that phenotypic mutations from yeast cluster at specific positions on protein domains, a characteristic previously revealed to be displayed by human disease mutations. We found over one hundred domain hotspots in yeast with approximately 50% in the exact same domain position as known human disease mutations. Conclusions We describe an analysis using protein domains as a framework for transferring functional information by studying domain hotspots in human and yeast and relating phenotypic changes in yeast to diseases in human. This first-of-a-kind study of phenotypically relevant yeast mutations in relation to human disease mutations demonstrates the utility of a multi-species analysis for advancing the understanding of the relationship between genetic mutations and phenotypic changes at the organismal level. PMID:23819456

Emergence of Huge Negative Spin-Transfer Torque in Atomically Thin Co layers

NASA Astrophysics Data System (ADS)

Je, Soong-Geun; Yoo, Sang-Cheol; Kim, Joo-Sung; Park, Yong-Keun; Park, Min-Ho; Moon, Joon; Min, Byoung-Chul; Choe, Sug-Bong

2017-04-01

Current-induced domain wall motion has drawn great attention in recent decades as the key operational principle of emerging magnetic memory devices. As the major driving force of the motion, the spin-orbit torque on chiral domain walls has been proposed and is currently extensively studied. However, we demonstrate here that there exists another driving force, which is larger than the spin-orbit torque in atomically thin Co films. Moreover, the direction of the present force is found to be the opposite of the prediction of the standard spin-transfer torque, resulting in the domain wall motion along the current direction. The symmetry of the force and its peculiar dependence on the domain wall structure suggest that the present force is, most likely, attributed to considerable enhancement of a negative nonadiabatic spin-transfer torque in ultranarrow domain walls. Careful measurements of the giant magnetoresistance manifest a negative spin polarization in the atomically thin Co films which might be responsible for the negative spin-transfer torque.

pH-dependent electron transfer reaction and direct bioelectrocatalysis of the quinohemoprotein pyranose dehydrogenase

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

Takeda, Kouta; Matsumura, Hirotoshi; Ishida, Takuya

A pyranose dehydrogenase from Coprinopsis cinerea (CcPDH) is an extracellular quinohemoeprotein, which consists a b-type cytochrome domain, a pyrroloquinoline-quinone (PQQ) domain, and a family 1-type carbohydrate-binding module. The electron transfer reaction of CcPDH was studied using some electron acceptors and a carbon electrode at various pH levels. Phenazine methosulfate (PMS) reacted directly at the PQQ domain, whereas cytochrome c (cyt c) reacted via the cytochrome domain of intact CcPDH. Thus, electrons are transferred from reduced PQQ in the catalytic domain of CcPDH to heme b in the N-terminal cytochrome domain, which acts as a built-in mediator and transfers electron tomore » a heterogenous electron transfer protein. The optimal pH values of the PMS reduction (pH 6.5) and the cyt c reduction (pH 8.5) differ. The catalytic currents for the oxidation of L-fucose were observed within a range of pH 4.5 to 11. Bioelectrocatalysis of CcPDH based on direct electron transfer demonstrated that the pH profile of the biocatalytic current was similar to the reduction activity of cyt c characters. - Highlights: • pH dependencies of activity were different for the reduction of cyt c and DCPIP. • DET-based bioelectrocatalysis of CcPDH was observed. • The similar pH-dependent profile was found with cyt c and electrode. • The present results suggested that IET reaction of CcPDH shows pH dependence.« less

Structural, Functional and Evolutionary Aspects of Seed Globulins.

PubMed

Kesari, Pooja; Neetu; Sharma, Anchal; Katiki, Madhusudhanarao; Kumar, Pramod; Gurjar, Bhola R; Tomar, Shailly; Sharma, Ashwani K; Kumar, Pravindra

2017-01-01

Globulins are a major class of seed storage proteins which were thought to be enzymatically inactive. These proteins belong to the most ancient cupin superfamily. They can be graded into 11S legumin type and 7S vicilin type based on their sedimentation coefficients. Members from both classes share structural homology are thought to have evolved from either one-domain germin predecessor by duplication or by horizontal gene transfer of two-domain gene from bacteria to eukaryotes. Globulins are known to define the nutritional quality of the seeds, however, they are also involved in sucrose binding, desiccation, defense against microbes, hormone binding and oxidative stress etc. Major drawback with globulins is their tendency to bind to IgE. Studying structural-functional behavior of such protein can help in modifying proteins for enhanced functionality in food processing industries. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo.

PubMed

Bergvall, Monika; Gagnon, David; Titolo, Steve; Lehoux, Michaël; D'Abramo, Claudia M; Melendy, Thomas; Archambault, Jacques

2016-01-06

The papillomavirus (PV) E1 helicase contains a conserved C-terminal domain (CTD), located next to its ATP-binding site, whose function in vivo is still poorly understood. The CTD is comprised of an alpha helix followed by an acidic region (AR) and a C-terminal extension termed the C-tail. Recent biochemical studies on bovine papillomavirus 1 (BPV1) E1 showed that the AR and C-tail regulate the oligomerization of the protein into a double hexamer at the origin. In this study, we assessed the importance of the CTD of human papillomavirus 11 (HPV11) E1 in vivo, using a cell-based DNA replication assay. Our results indicate that combined deletion of the AR and C-tail drastically reduces DNA replication, by 85%, and that further truncation into the alpha-helical region compromises the structural integrity of the E1 helicase domain and its interaction with E2. Surprisingly, removal of the C-tail alone or mutation of highly conserved residues within the domain still allows significant levels of DNA replication (55%). This is in contrast to the absolute requirement for the C-tail reported for BPV1 E1 in vitro and confirmed here in vivo. Characterization of chimeric proteins in which the AR and C-tail from HPV11 E1 were replaced by those of BPV1 indicated that while the function of the AR is transferable, that of the C-tail is not. Collectively, these findings define the contribution of the three CTD subdomains to the DNA replication activity of E1 in vivo and suggest that the function of the C-tail has evolved in a PV type-specific manner. While much is known about hexameric DNA helicases from superfamily 3, the papillomavirus E1 helicase contains a unique C-terminal domain (CTD) adjacent to its ATP-binding site. We show here that this CTD is important for the DNA replication activity of HPV11 E1 in vivo and that it can be divided into three functional subdomains that roughly correspond to the three conserved regions of the CTD: an alpha helix, needed for the structural integrity of the helicase domain, followed by an acidic region (AR) and a C-terminal tail (C-tail) that have been shown to regulate the oligomerization of BPV1 E1 in vitro. Characterization of E1 chimeras revealed that, while the function of the AR could be transferred from BPV1 E1 to HPV11 E1, that of the C-tail could not. These results suggest that the E1 CTD performs multiple functions in DNA replication, some of them in a virus type-specific manner. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo

PubMed Central

Bergvall, Monika; Gagnon, David; Titolo, Steve; Lehoux, Michaël; D'Abramo, Claudia M.

2016-01-01

ABSTRACT The papillomavirus (PV) E1 helicase contains a conserved C-terminal domain (CTD), located next to its ATP-binding site, whose function in vivo is still poorly understood. The CTD is comprised of an alpha helix followed by an acidic region (AR) and a C-terminal extension termed the C-tail. Recent biochemical studies on bovine papillomavirus 1 (BPV1) E1 showed that the AR and C-tail regulate the oligomerization of the protein into a double hexamer at the origin. In this study, we assessed the importance of the CTD of human papillomavirus 11 (HPV11) E1 in vivo, using a cell-based DNA replication assay. Our results indicate that combined deletion of the AR and C-tail drastically reduces DNA replication, by 85%, and that further truncation into the alpha-helical region compromises the structural integrity of the E1 helicase domain and its interaction with E2. Surprisingly, removal of the C-tail alone or mutation of highly conserved residues within the domain still allows significant levels of DNA replication (55%). This is in contrast to the absolute requirement for the C-tail reported for BPV1 E1 in vitro and confirmed here in vivo. Characterization of chimeric proteins in which the AR and C-tail from HPV11 E1 were replaced by those of BPV1 indicated that while the function of the AR is transferable, that of the C-tail is not. Collectively, these findings define the contribution of the three CTD subdomains to the DNA replication activity of E1 in vivo and suggest that the function of the C-tail has evolved in a PV type-specific manner. IMPORTANCE While much is known about hexameric DNA helicases from superfamily 3, the papillomavirus E1 helicase contains a unique C-terminal domain (CTD) adjacent to its ATP-binding site. We show here that this CTD is important for the DNA replication activity of HPV11 E1 in vivo and that it can be divided into three functional subdomains that roughly correspond to the three conserved regions of the CTD: an alpha helix, needed for the structural integrity of the helicase domain, followed by an acidic region (AR) and a C-terminal tail (C-tail) that have been shown to regulate the oligomerization of BPV1 E1 in vitro. Characterization of E1 chimeras revealed that, while the function of the AR could be transferred from BPV1 E1 to HPV11 E1, that of the C-tail could not. These results suggest that the E1 CTD performs multiple functions in DNA replication, some of them in a virus type-specific manner. PMID:26739052

A concept ideation framework for medical device design.

PubMed

Hagedorn, Thomas J; Grosse, Ian R; Krishnamurty, Sundar

2015-06-01

Medical device design is a challenging process, often requiring collaboration between medical and engineering domain experts. This collaboration can be best institutionalized through systematic knowledge transfer between the two domains coupled with effective knowledge management throughout the design innovation process. Toward this goal, we present the development of a semantic framework for medical device design that unifies a large medical ontology with detailed engineering functional models along with the repository of design innovation information contained in the US Patent Database. As part of our development, existing medical, engineering, and patent document ontologies were modified and interlinked to create a comprehensive medical device innovation and design tool with appropriate properties and semantic relations to facilitate knowledge capture, enrich existing knowledge, and enable effective knowledge reuse for different scenarios. The result is a Concept Ideation Framework for Medical Device Design (CIFMeDD). Key features of the resulting framework include function-based searching and automated inter-domain reasoning to uniquely enable identification of functionally similar procedures, tools, and inventions from multiple domains based on simple semantic searches. The significance and usefulness of the resulting framework for aiding in conceptual design and innovation in the medical realm are explored via two case studies examining medical device design problems. Copyright © 2015 Elsevier Inc. All rights reserved.

The tetramerization domain potentiates Kv4 channel function by suppressing closed-state inactivation.

PubMed

Tang, Yi-Quan; Zhou, Jing-Heng; Yang, Fan; Zheng, Jie; Wang, KeWei

2014-09-02

A-type Kv4 potassium channels undergo a conformational change toward a nonconductive state at negative membrane potentials, a dynamic process known as pre-open closed states or closed-state inactivation (CSI). CSI causes inhibition of channel activity without the prerequisite of channel opening, thus providing a dynamic regulation of neuronal excitability, dendritic signal integration, and synaptic plasticity at resting. However, the structural determinants underlying Kv4 CSI remain largely unknown. We recently showed that the auxiliary KChIP4a subunit contains an N-terminal Kv4 inhibitory domain (KID) that directly interacts with Kv4.3 channels to enhance CSI. In this study, we utilized the KChIP4a KID to probe key structural elements underlying Kv4 CSI. Using fluorescence resonance energy transfer two-hybrid mapping and bimolecular fluorescence complementation-based screening combined with electrophysiology, we identified the intracellular tetramerization (T1) domain that functions to suppress CSI and serves as a receptor for the binding of KID. Disrupting the Kv4.3 T1-T1 interaction interface by mutating C110A within the C3H1 motif of T1 domain facilitated CSI and ablated the KID-mediated enhancement of CSI. Furthermore, replacing the Kv4.3 T1 domain with the T1 domain from Kv1.4 (without the C3H1 motif) or Kv2.1 (with the C3H1 motif) resulted in channels functioning with enhanced or suppressed CSI, respectively. Taken together, our findings reveal a novel (to our knowledge) role of the T1 domain in suppressing Kv4 CSI, and that KChIP4a KID directly interacts with the T1 domain to facilitate Kv4.3 CSI, thus leading to inhibition of channel function. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Murt user`s guide: A hybrid Lagrangian-Eulerian finite element model of multiple-pore-region solute transport through subsurface media

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

Gwo, J.P.; Jardine, P.M.; Yeh, G.T.

Matrix diffusion, a diffusive mass transfer process,in the structured soils and geologic units at ORNL, is believe to be an important subsurface mass transfer mechanism; it may affect off-site movement of radioactive wastes and remediation of waste disposal sites by locally exchanging wastes between soil/rock matrix and macropores/fractures. Advective mass transfer also contributes to waste movement but is largely neglected by researchers. This report presents the first documented 2-D multiregion solute transport code (MURT) that incorporates not only diffusive but also advective mass transfer and can be applied to heterogeneous porous media under transient flow conditions. In this report, theoreticalmore » background is reviewed and the derivation of multiregion solute transport equations is presented. Similar to MURF (Gwo et al. 1994), a multiregion subsurface flow code, multiplepore domains as suggested by previous investigators (eg, Wilson and Luxmoore 1988) can be implemented in MURT. Transient or steady-state flow fields of the pore domains can be either calculated by MURF or by modelers. The mass transfer process is briefly discussed through a three-pore-region multiregion solute transport mechanism. Mass transfer equations that describe mass flux across pore region interfaces are also presented and parameters needed to calculate mass transfer coefficients detailed. Three applications of MURT (tracer injection problem, sensitivity analysis of advective and diffusive mass transfer, hillslope ponding infiltration and secondary source problem) were simulated and results discussed. Program structure of MURT and functions of MURT subroutiness are discussed so that users can adapt the code; guides for input data preparation are provided in appendices.« less

Giant oscillating magnetoresistance in silicene-based structures

NASA Astrophysics Data System (ADS)

Oubram, O.; Navarro, O.; Rodríguez-Vargas, I.; Guzman, E. J.; Cisneros-Villalobos, L.; Velásquez-Aguilar, J. G.

2018-02-01

Ballistic electron transport in a silicene structure, composed of a pair of magnetic gates, in the ferromagnetic and an-tiferromagnetic configuration is studied. This theoretical study has been done using the matrix transfer method to calculate the transmission, the conductance for parallel and antiparallel magnetic alignment and the magnetoresistance. Results show that conductance and magnetoresistance oscillate as a function of the length between the two magnetic domains. The forbidden transmission region also increases as a function of the barrier separation distance.

Gain dynamics of clad-pumped Yb-fiber amplifier and intensity noise control.

PubMed

Zhao, Jian; Guiraud, Germain; Floissat, Florian; Gouhier, Benoit; Rota-Rodrigo, Sergio; Traynor, Nicholas; Santarelli, Giorgio

2017-01-09

Gain dynamics study provides an attractive method to understand the intensity noise behavior in fiber amplifiers. Here, the gain dynamics of a medium power (5 W) clad-pumped Yb-fiber amplifier is experimentally evaluated by measuring the frequency domain transfer functions for the input seed and pump lasers from 10 Hz to 1 MHz. We study gain dynamic behavior of the fiber amplifier in the presence of significant residual pump power (compared to the seed power), showing that the seed transfer function is strongly saturated at low Fourier frequencies while the pump power modulation transfer function is nearly unaffected. The characterization of relative intensity noise (RIN) of the fiber amplifier is well explained by the gain dynamics analysis. Finally, a 600 kHz bandwidth feedback loop using an acoustic-optical modulator (AOM) controlling the seed intensity is successfully demonstrated to suppress the broadband laser intensity noise. A maximum noise reduction of about 30 dB is achieved leading to a RIN of -152 dBc/Hz (~1 kHz-10 MHz) at 2.5 W output power.

Iterated intracochlear reflection shapes the envelopes of basilar-membrane click responses

PubMed Central

Shera, Christopher A.

2015-01-01

Multiple internal reflection of cochlear traveling waves has been argued to provide a plausible explanation for the waxing and waning and other temporal structures often exhibited by the envelopes of basilar-membrane (BM) and auditory-nerve responses to acoustic clicks. However, a recent theoretical analysis of a BM click response measured in chinchilla concludes that the waveform cannot have arisen via any equal, repetitive process, such as iterated intracochlear reflection [Wit and Bell (2015), J. Acoust. Soc. Am. 138, 94–96]. Reanalysis of the waveform contradicts this conclusion. The measured BM click response is used to derive the frequency-domain transfer function characterizing every iteration of the loop. The selfsame transfer function that yields waxing and waning of the BM click response also captures the spectral features of ear-canal stimulus-frequency otoacoustic emissions measured in the same animal, consistent with the predictions of multiple internal reflection. Small shifts in transfer-function phase simulate results at different measurement locations and reproduce the heterogeneity of BM click response envelopes observed experimentally. PMID:26723327

Introduction to Flight Test Engineering (Introduction aux techniques des essais en vol)

DTIC Science & Technology

2005-07-01

or aircraft parameters • Calculations in the frequency domain ( Fast Fourier Transform) • Data analysis with dedicated software for: • Signal...density Fast Fourier Transform Transfer function analysis Frequency response analysis Etc. PRESENTATION Color/black & white Display screen...envelope by operating the airplane at increasing ranges - representing increasing risk - of engine operation, airspeeds both fast and slow, altitude

Functional properties and structural requirements of the plasmid pMV158-encoded MobM relaxase domain.

PubMed

Fernández-López, Cris; Pluta, Radoslaw; Pérez-Luque, Rosa; Rodríguez-González, Lorena; Espinosa, Manuel; Coll, Miquel; Lorenzo-Díaz, Fabián; Boer, D Roeland

2013-07-01

A crucial element in the horizontal transfer of mobilizable and conjugative plasmids is the relaxase, a single-stranded endonuclease that nicks the origin of transfer (oriT) of the plasmid DNA. The relaxase of the pMV158 mobilizable plasmid is MobM (494 residues). In solution, MobM forms a dimer through its C-terminal domain, which is proposed to anchor the protein to the cell membrane and to participate in type 4 secretion system (T4SS) protein-protein interactions. In order to gain a deeper insight into the structural MobM requirements for efficient DNA catalysis, we studied two endonuclease domain variants that include the first 199 or 243 amino acid residues (MobMN199 and MobMN243, respectively). Our results confirmed that the two proteins behaved as monomers in solution. Interestingly, MobMN243 relaxed supercoiled DNA and cleaved single-stranded oligonucleotides harboring oriTpMV158, whereas MobMN199 was active only on supercoiled DNA. Protein stability studies using gel electrophoresis and mass spectrometry showed increased susceptibility to degradation at the domain boundary between the N- and C-terminal domains, suggesting that the domains change their relative orientation upon DNA binding. Overall, these results demonstrate that MobMN243 is capable of nicking the DNA substrate independently of its topology and that the amino acids 200 to 243 modulate substrate specificity but not the nicking activity per se. These findings suggest that these amino acids are involved in positioning the DNA for the nuclease reaction rather than in the nicking mechanism itself.

Power cepstrum technique with application to model helicopter acoustic data

NASA Technical Reports Server (NTRS)

Martin, R. M.; Burley, C. L.

1986-01-01

The application of the power cepstrum to measured helicopter-rotor acoustic data is investigated. A previously applied correction to the reconstructed spectrum is shown to be incorrect. For an exact echoed signal, the amplitude of the cepstrum echo spike at the delay time is linearly related to the echo relative amplitude in the time domain. If the measured spectrum is not entirely from the source signal, the cepstrum will not yield the desired echo characteristics and a cepstral aliasing may occur because of the effective sample rate in the frequency domain. The spectral analysis bandwidth must be less than one-half the echo ripple frequency or cepstral aliasing can occur. The power cepstrum editing technique is a useful tool for removing some of the contamination because of acoustic reflections from measured rotor acoustic spectra. The cepstrum editing yields an improved estimate of the free field spectrum, but the correction process is limited by the lack of accurate knowledge of the echo transfer function. An alternate procedure, which does not require cepstral editing, is proposed which allows the complete correction of a contaminated spectrum through use of both the transfer function and delay time of the echo process.

Stage-by-Stage and Parallel Flow Path Compressor Modeling for a Variable Cycle Engine, NASA Advanced Air Vehicles Program - Commercial Supersonic Technology Project - AeroServoElasticity

NASA Technical Reports Server (NTRS)

Kopasakis, George; Connolly, Joseph W.; Cheng, Larry

2015-01-01

This paper covers the development of stage-by-stage and parallel flow path compressor modeling approaches for a Variable Cycle Engine. The stage-by-stage compressor modeling approach is an extension of a technique for lumped volume dynamics and performance characteristic modeling. It was developed to improve the accuracy of axial compressor dynamics over lumped volume dynamics modeling. The stage-by-stage compressor model presented here is formulated into a parallel flow path model that includes both axial and rotational dynamics. This is done to enable the study of compressor and propulsion system dynamic performance under flow distortion conditions. The approaches utilized here are generic and should be applicable for the modeling of any axial flow compressor design accurate time domain simulations. The objective of this work is as follows. Given the parameters describing the conditions of atmospheric disturbances, and utilizing the derived formulations, directly compute the transfer function poles and zeros describing these disturbances for acoustic velocity, temperature, pressure, and density. Time domain simulations of representative atmospheric turbulence can then be developed by utilizing these computed transfer functions together with the disturbance frequencies of interest.

Strand transfer inhibitors of HIV-1 integrase: bringing IN a new era of antiretroviral therapy.

PubMed

McColl, Damian J; Chen, Xiaowu

2010-01-01

HIV-1 integrase (IN) is one of three essential enzymes (along with reverse transcriptase and protease) encoded by the viral pol gene. IN mediates two critical reactions during viral replication; firstly 3'-end processing (3'EP) of the double-stranded viral DNA ends and then strand transfer (STF) which joins the viral DNA to the host chromosomal DNA forming a functional integrated proviral DNA. IN is a 288 amino acid protein containing three functional domains, the N-terminal domain (NTD), catalytic core domain (CCD) and the C-terminal domain (CTD). The CCD contains three conserved catalytic residues, Asp64, Asp116 and Glu152, which coordinate divalent metal ions essential for the STF reaction. Intensive research over the last two decades has led to the discovery and development of small molecule inhibitors of the IN STF reaction (INSTIs). INSTIs are catalytic inhibitors of IN, and act to chelate the divalent metal ions in the CCD. One INSTI, raltegravir (RAL, Merck Inc.) was approved in late 2007 for the treatment of HIV-1 infection in patients with prior antiretroviral (ARV) treatment experience and was recently approved also for first line therapy. A second INSTI, elvitegravir (EVG, Gilead Sciences, Inc.) is currently undergoing phase 3 studies in ARV treatment-experienced patients and phase 2 studies in ARV naïve patients as part of a novel fixed dose combination. Several additional INSTIs are in early stage clinical development. This review will discuss the discovery and development of this novel class of antiretrovirals. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010. Copyright 2009. Published by Elsevier B.V.

Slow domain reconfiguration causes power-law kinetics in a two-state enzyme.

PubMed

Grossman-Haham, Iris; Rosenblum, Gabriel; Namani, Trishool; Hofmann, Hagen

2018-01-16

Protein dynamics are typically captured well by rate equations that predict exponential decays for two-state reactions. Here, we describe a remarkable exception. The electron-transfer enzyme quiescin sulfhydryl oxidase (QSOX), a natural fusion of two functionally distinct domains, switches between open- and closed-domain arrangements with apparent power-law kinetics. Using single-molecule FRET experiments on time scales from nanoseconds to milliseconds, we show that the unusual open-close kinetics results from slow sampling of an ensemble of disordered domain orientations. While substrate accelerates the kinetics, thus suggesting a substrate-induced switch to an alternative free energy landscape of the enzyme, the power-law behavior is also preserved upon electron load. Our results show that the slow sampling of open conformers is caused by a variety of interdomain interactions that imply a rugged free energy landscape, thus providing a generic mechanism for dynamic disorder in multidomain enzymes.

Structure and function of Hip, an attenuator of the Hsp70 chaperone cycle.

PubMed

Li, Zhuo; Hartl, F Ulrich; Bracher, Andreas

2013-08-01

The Hsp70-interacting protein, Hip, cooperates with the chaperone Hsp70 in protein folding and prevention of aggregation. Hsp70 interacts with non-native protein substrates in an ATP-dependent reaction cycle regulated by J-domain proteins and nucleotide exchange factors (NEFs). Hip is thought to delay substrate release by slowing ADP dissociation from Hsp70. Here we present crystal structures of the dimerization domain and the tetratricopeptide repeat (TPR) domain of rat Hip. As shown in a cocrystal structure, the TPR core of Hip interacts with the Hsp70 ATPase domain through an extensive interface, to form a bracket that locks ADP in the binding cleft. Hip and NEF binding to Hsp70 are mutually exclusive, and thus Hip attenuates active cycling of Hsp70-substrate complexes. This mechanism explains how Hip enhances aggregation prevention by Hsp70 and facilitates transfer of specific proteins to downstream chaperones or the proteasome.

Substructural Regularization With Data-Sensitive Granularity for Sequence Transfer Learning.

PubMed

Sun, Shichang; Liu, Hongbo; Meng, Jiana; Chen, C L Philip; Yang, Yu

2018-06-01

Sequence transfer learning is of interest in both academia and industry with the emergence of numerous new text domains from Twitter and other social media tools. In this paper, we put forward the data-sensitive granularity for transfer learning, and then, a novel substructural regularization transfer learning model (STLM) is proposed to preserve target domain features at substructural granularity in the light of the condition of labeled data set size. Our model is underpinned by hidden Markov model and regularization theory, where the substructural representation can be integrated as a penalty after measuring the dissimilarity of substructures between target domain and STLM with relative entropy. STLM can achieve the competing goals of preserving the target domain substructure and utilizing the observations from both the target and source domains simultaneously. The estimation of STLM is very efficient since an analytical solution can be derived as a necessary and sufficient condition. The relative usability of substructures to act as regularization parameters and the time complexity of STLM are also analyzed and discussed. Comprehensive experiments of part-of-speech tagging with both Brown and Twitter corpora fully justify that our model can make improvements on all the combinations of source and target domains.

[Invitation to the immunoglobulin world].

PubMed

Mafune, Naoki

2010-04-01

One of the most basic characteristics of the organism is to recognize self and non-self. Immune system is a typical system that fulfills this characteristic, and the immunoglobulins play important roles in it. The immunoglobulins circulating in internal or secreting to external space of the body, are basically characterized as a soluble form of cell surface receptors. The immunoglobulin has two kinds of domains. One is the variable domain that binds the antigen and the other is the constant domain that has the effecter functions. The immunoglobulin molecule can be obviously identified in vertebrates. In mammals, five immunoglobulin classes, IgG, IgA, IgM, IgD and IgE are classified. It is important to recognize that our immune system assign immunological roles among classes especially between IgG and IgA after class switch from IgM. IgG, the major immunoglobulin in plasma or extra vascular spaces, has the most versatile function of immunoglobulin molecules; such as placenta transfer, complement fixation and cell binding. On the other hand, IgA, the major immunoglobulin in secretions, does not show any complement fixation unless denatured. These facts implicate an aggressive characteristic of IgG in systemic immune response inside of the body, and a defensive characteristic of IgA in mucosal immune response on the surface of the body. Further, they allot the immunological roles to fetus or baby, in other words, IgG transferred from placenta protects fetus and newborn, and then IgA secreted in milk protects baby from mucosal invasion of pathogenic organisms.

A study of the dynamics of seizure propagation across micro domains in the vicinity of the seizure onset zone

PubMed Central

Basu, Ishita; Kudela, Pawel; Korzeniewska, Anna; Franaszczuk, Piotr J.; Anderson, William S.

2015-01-01

Objective The use of micro-electrode arrays to measure electrical activity from the surface of the brain is increasingly being investigated as a means to improve seizure onset zone localization. In this work, we used a multivariate autoregressive model to determine the evolution of seizure dynamics in the 70 – 110 Hz high frequency band across micro-domains sampled by such micro-electrode arrays. Approach We used 7 complex partial seizures recorded from 4 patients undergoing intracranial monitoring for surgical evaluation to reconstruct the seizure propagation pattern over sliding windows using a directed transfer function measure. Main results We showed that a directed transfer function can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with known propagation pattern. In general, depending on the location of the micro-electrode grid with respect to the clinical seizure onset zone and the time from seizure onset, ictal propagation changed in directional characteristics over a 2 to 10 seconds time scale, with gross directionality limited to spatial dimensions of approximately 9mm2. It was also seen that the strongest seizure patterns in the high frequency band and their sources over such micro-domains are more stable over time and across seizures bordering the clinically determined seizure onset zone than inside. Significance This type of propagation analysis might in future provide an additional tool to epileptologists for characterizing epileptogenic tissue. This will potentially help narrowing down resection zones without compromising essential brain functions as well as provide important information about targeting anti-epileptic stimulation devices. PMID:26061006

Conformational State Distributions and Catalytically Relevant Dynamics of a Hinge-Bending Enzyme Studied by Single-Molecule FRET and a Coarse-Grained Simulation

PubMed Central

Gabba, Matteo; Poblete, Simón; Rosenkranz, Tobias; Katranidis, Alexandros; Kempe, Daryan; Züchner, Tina; Winkler, Roland G.; Gompper, Gerhard; Fitter, Jörg

2014-01-01

Over the last few decades, a view has emerged showing that multidomain enzymes are biological machines evolved to harness stochastic kicks of solvent particles into highly directional functional motions. These intrinsic motions are structurally encoded, and Nature makes use of them to catalyze chemical reactions by means of ligand-induced conformational changes and states redistribution. Such mechanisms align reactive groups for efficient chemistry and stabilize conformers most proficient for catalysis. By combining single-molecule Förster resonance energy transfer measurements with normal mode analysis and coarse-grained mesoscopic simulations, we obtained results for a hinge-bending enzyme, namely phosphoglycerate kinase (PGK), which support and extend these ideas. From single-molecule Förster resonance energy transfer, we obtained insight into the distribution of conformational states and the dynamical properties of the domains. The simulations allowed for the characterization of interdomain motions of a compact state of PGK. The data show that PGK is intrinsically a highly dynamic system sampling a wealth of conformations on timescales ranging from nanoseconds to milliseconds and above. Functional motions encoded in the fold are performed by the PGK domains already in its ligand-free form, and substrate binding is not required to enable them. Compared to other multidomain proteins, these motions are rather fast and presumably not rate-limiting in the enzymatic reaction. Ligand binding slightly readjusts the orientation of the domains and feasibly locks the protein motions along a preferential direction. In addition, the functionally relevant compact state is stabilized by the substrates, and acts as a prestate to reach active conformations by means of Brownian motions. PMID:25418172

Performance Analysis of Triple Asymmetrical Optical Micro Ring Resonator with 2 × 2 Input-Output Bus Waveguide

NASA Astrophysics Data System (ADS)

Ranjan, Suman; Mandal, Sanjoy

2017-12-01

Modeling of triple asymmetrical optical micro ring resonator (TAOMRR) in z-domain with 2 × 2 input-output system with detailed design of its waveguide configuration using finite-difference time-domain (FDTD) method is presented. Transfer function in z-domain using delay-line signal processing technique of the proposed TAOMRR is determined for different input and output ports. The frequency response analysis is carried out using MATLAB software. Group delay and dispersion characteristics are also determined in MATLAB. The electric field analysis is done using FDTD. The method proposes a new methodology to design and draw multiple configurations of coupled ring resonators having multiple in and out ports. Various important parameters such as coupling coefficients and FSR are also determined.

Performance Analysis of Triple Asymmetrical Optical Micro Ring Resonator with 2 × 2 Input-Output Bus Waveguide

NASA Astrophysics Data System (ADS)

Ranjan, Suman; Mandal, Sanjoy

2018-02-01

Modeling of triple asymmetrical optical micro ring resonator (TAOMRR) in z-domain with 2 × 2 input-output system with detailed design of its waveguide configuration using finite-difference time-domain (FDTD) method is presented. Transfer function in z-domain using delay-line signal processing technique of the proposed TAOMRR is determined for different input and output ports. The frequency response analysis is carried out using MATLAB software. Group delay and dispersion characteristics are also determined in MATLAB. The electric field analysis is done using FDTD. The method proposes a new methodology to design and draw multiple configurations of coupled ring resonators having multiple in and out ports. Various important parameters such as coupling coefficients and FSR are also determined.

ChemTrove: enabling a generic ELN to support chemistry through the use of transferable plug-ins and online data sources.

PubMed

Day, Aileen E; Coles, Simon J; Bird, Colin L; Frey, Jeremy G; Whitby, Richard J; Tkachenko, Valery E; Williams, Antony J

2015-03-23

In designing an Electronic Lab Notebook (ELN), there is a balance to be struck between keeping it as general and multidisciplinary as possible for simplicity of use and maintenance and introducing more domain-specific functionality to increase its appeal to target research areas. Here, we describe the results of a collaboration between the Royal Society of Chemistry (RSC) and the University of Southampton, guided by the aims of the Dial-a-Molecule Grand Challenge, intended to achieve the best of both worlds and augment a discipline-agnostic ELN, LabTrove, with chemistry-specific functionality and using data provided by the ChemSpider platform. This has been done using plug-in technology to ensure maximum transferability with minimal effort of the chemistry functionality to other ELNs and equally other subject-specific functionality to LabTrove. The resulting product, ChemTrove, has undergone a usability trial by selected academics, and the resulting feedback will guide the future development of the underlying ELN technology.

Defining ICR-Mo, an intrinsic colistin resistance determinant from Moraxella osloensis.

PubMed

Wei, Wenhui; Srinivas, Swaminath; Lin, Jingxia; Tang, Zichen; Wang, Shihua; Ullah, Saif; Kota, Vishnu Goutham; Feng, Youjun

2018-05-14

Polymyxin is the last line of defense against severe infections caused by carbapenem-resistant gram-negative pathogens. The emergence of transferable MCR-1/2 polymyxin resistance greatly challenges the renewed interest in colistin (polymyxin E) for clinical treatments. Recent studies have suggested that Moraxella species are a putative reservoir for MCR-1/2 genetic determinants. Here, we report the functional definition of ICR-Mo from M. osloensis, a chromosomally encoded determinant of colistin resistance, in close relation to current MCR-1/2 family. ICR-Mo transmembrane protein was prepared and purified to homogeneity. Taken along with an in vitro enzymatic detection, MALDI-TOF mass spectrometry of bacterial lipid A pools determined that the ICR-Mo enzyme might exploit a possible "ping-pong" mechanism to accept the phosphoethanolamine (PEA) moiety from its donor phosphatidylethanolamine (PE) and then transfer it to the 1(or 4')-phosphate position of lipid A via an ICR-Mo-bound PEA adduct. Structural decoration of LPS-lipid A by ICR-Mo renders the recipient strain of E. coli resistant to polymyxin. Domain swapping assays indicate that the two domains of ICR-Mo cannot be functionally-exchanged with its counterparts in MCR-1/2 and EptA, validating its phylogenetic position in a distinct set of MCR-like genes. Structure-guided functional mapping of ICR-Mo reveals a PE lipid substrate recognizing cavity having a role in enzymatic catalysis and the resultant conference of antibiotic resistance. Expression of icr-Mo in E. coli significantly prevents the formation of reactive oxygen species (ROS) induced by colistin. Taken together, our results define a member of a group of intrinsic colistin resistance genes phylogenetically close to the MCR-1/2 family, highlighting the evolution of transferable colistin resistance.

Transfer of Training between Music and Speech: Common Processing, Attention, and Memory.

PubMed

Besson, Mireille; Chobert, Julie; Marie, Céline

2011-01-01

After a brief historical perspective of the relationship between language and music, we review our work on transfer of training from music to speech that aimed at testing the general hypothesis that musicians should be more sensitive than non-musicians to speech sounds. In light of recent results in the literature, we argue that when long-term experience in one domain influences acoustic processing in the other domain, results can be interpreted as common acoustic processing. But when long-term experience in one domain influences the building-up of abstract and specific percepts in another domain, results are taken as evidence for transfer of training effects. Moreover, we also discuss the influence of attention and working memory on transfer effects and we highlight the usefulness of the event-related potentials method to disentangle the different processes that unfold in the course of music and speech perception. Finally, we give an overview of an on-going longitudinal project with children aimed at testing transfer effects from music to different levels and aspects of speech processing.

Transfer of Training between Music and Speech: Common Processing, Attention, and Memory

PubMed Central

Besson, Mireille; Chobert, Julie; Marie, Céline

2011-01-01

After a brief historical perspective of the relationship between language and music, we review our work on transfer of training from music to speech that aimed at testing the general hypothesis that musicians should be more sensitive than non-musicians to speech sounds. In light of recent results in the literature, we argue that when long-term experience in one domain influences acoustic processing in the other domain, results can be interpreted as common acoustic processing. But when long-term experience in one domain influences the building-up of abstract and specific percepts in another domain, results are taken as evidence for transfer of training effects. Moreover, we also discuss the influence of attention and working memory on transfer effects and we highlight the usefulness of the event-related potentials method to disentangle the different processes that unfold in the course of music and speech perception. Finally, we give an overview of an on-going longitudinal project with children aimed at testing transfer effects from music to different levels and aspects of speech processing. PMID:21738519

Accurate reconstruction of the optical parameter distribution in participating medium based on the frequency-domain radiative transfer equation

NASA Astrophysics Data System (ADS)

Qiao, Yao-Bin; Qi, Hong; Zhao, Fang-Zhou; Ruan, Li-Ming

2016-12-01

Reconstructing the distribution of optical parameters in the participating medium based on the frequency-domain radiative transfer equation (FD-RTE) to probe the internal structure of the medium is investigated in the present work. The forward model of FD-RTE is solved via the finite volume method (FVM). The regularization term formatted by the generalized Gaussian Markov random field model is used in the objective function to overcome the ill-posed nature of the inverse problem. The multi-start conjugate gradient (MCG) method is employed to search the minimum of the objective function and increase the efficiency of convergence. A modified adjoint differentiation technique using the collimated radiative intensity is developed to calculate the gradient of the objective function with respect to the optical parameters. All simulation results show that the proposed reconstruction algorithm based on FD-RTE can obtain the accurate distributions of absorption and scattering coefficients. The reconstructed images of the scattering coefficient have less errors than those of the absorption coefficient, which indicates the former are more suitable to probing the inner structure. Project supported by the National Natural Science Foundation of China (Grant No. 51476043), the Major National Scientific Instruments and Equipment Development Special Foundation of China (Grant No. 51327803), and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (Grant No. 51121004).

Coupled numerical approach combining finite volume and lattice Boltzmann methods for multi-scale multi-physicochemical processes

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

Chen, Li; He, Ya-Ling; Kang, Qinjun

2013-12-15

A coupled (hybrid) simulation strategy spatially combining the finite volume method (FVM) and the lattice Boltzmann method (LBM), called CFVLBM, is developed to simulate coupled multi-scale multi-physicochemical processes. In the CFVLBM, computational domain of multi-scale problems is divided into two sub-domains, i.e., an open, free fluid region and a region filled with porous materials. The FVM and LBM are used for these two regions, respectively, with information exchanged at the interface between the two sub-domains. A general reconstruction operator (RO) is proposed to derive the distribution functions in the LBM from the corresponding macro scalar, the governing equation of whichmore » obeys the convection–diffusion equation. The CFVLBM and the RO are validated in several typical physicochemical problems and then are applied to simulate complex multi-scale coupled fluid flow, heat transfer, mass transport, and chemical reaction in a wall-coated micro reactor. The maximum ratio of the grid size between the FVM and LBM regions is explored and discussed. -- Highlights: •A coupled simulation strategy for simulating multi-scale phenomena is developed. •Finite volume method and lattice Boltzmann method are coupled. •A reconstruction operator is derived to transfer information at the sub-domains interface. •Coupled multi-scale multiple physicochemical processes in micro reactor are simulated. •Techniques to save computational resources and improve the efficiency are discussed.« less

Unique Helicase Determinants in the Essential Conjugative TraI Factor from Salmonella enterica Serovar Typhimurium Plasmid pCU1

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

McLaughlin, K. J.; Nash, R. P.; Redinbo, M. R.

The widespread development of multidrug-resistant bacteria is a major health emergency. Conjugative DNA plasmids, which harbor a wide range of antibiotic resistance genes, also encode the protein factors necessary to orchestrate the propagation of plasmid DNA between bacterial cells through conjugative transfer. Successful conjugative DNA transfer depends on key catalytic components to nick one strand of the duplex DNA plasmid and separate the DNA strands while cell-to-cell transfer occurs. The TraI protein from the conjugative Salmonella plasmid pCU1 fulfills these key catalytic roles, as it contains both single-stranded DNA-nicking relaxase and ATP-dependent helicase domains within a single, 1,078-residue polypeptide. Inmore » this work, we unraveled the helicase determinants of Salmonella pCU1 TraI through DNA binding, ATPase, and DNA strand separation assays. TraI binds DNA substrates with high affinity in a manner influenced by nucleic acid length and the presence of a DNA hairpin structure adjacent to the nick site. TraI selectively hydrolyzes ATP, and mutations in conserved helicase motifs eliminate ATPase activity. Surprisingly, the absence of a relatively short (144-residue) domain at the extreme C terminus of the protein severely diminishes ATP-dependent strand separation. Collectively, these data define the helicase motifs of the conjugative factor TraI from Salmonella pCU1 and reveal a previously uncharacterized C-terminal functional domain that uncouples ATP hydrolysis from strand separation activity.« less

Memory and language improvements following cognitive control training.

PubMed

Hussey, Erika K; Harbison, J Isaiah; Teubner-Rhodes, Susan E; Mishler, Alan; Velnoskey, Kayla; Novick, Jared M

2017-01-01

Cognitive control refers to adjusting thoughts and actions when confronted with conflict during information processing. We tested whether this ability is causally linked to performance on certain language and memory tasks by using cognitive control training to systematically modulate people's ability to resolve information-conflict across domains. Different groups of subjects trained on 1 of 3 minimally different versions of an n-back task: n-back-with-lures (High-Conflict), n-back-without-lures (Low-Conflict), or 3-back-without-lures (3-Back). Subjects completed a battery of recognition memory and language processing tasks that comprised both high- and low-conflict conditions before and after training. We compared the transfer profiles of (a) the High- versus Low-Conflict groups to test how conflict resolution training contributes to transfer effects, and (b) the 3-Back versus Low-Conflict groups to test for differences not involving cognitive control. High-Conflict training-but not Low-Conflict training-produced discernable benefits on several untrained transfer tasks, but only under selective conditions requiring cognitive control. This suggests that the conflict-focused intervention influenced functioning on ostensibly different outcome measures across memory and language domains. 3-Back training resulted in occasional improvements on the outcome measures, but these were not selective for conditions involving conflict resolution. We conclude that domain-general cognitive control mechanisms are plastic, at least temporarily, and may play a causal role in linguistic and nonlinguistic performance. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Linear control theory for gene network modeling.

PubMed

Shin, Yong-Jun; Bleris, Leonidas

2010-09-16

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

The X-ray Crystallographic Structure and Activity Analysis of a Pseudomonas-Specific Subfamily of the HAD Enzyme Superfamily Evidences a Novel Biochemical Function

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

Peisach,E.; Wang, L.; Burroughs, A.

2008-01-01

The haloacid dehalogenase (HAD) superfamily is a large family of proteins dominated by phosphotransferases. Thirty-three sequence families within the HAD superfamily (HADSF) have been identified to assist in function assignment. One such family includes the enzyme phosphoacetaldehyde hydrolase (phosphonatase). Phosphonatase possesses the conserved Rossmanniod core domain and a C1-type cap domain. Other members of this family do not possess a cap domain and because the cap domain of phosphonatase plays an important role in active site desolvation and catalysis, the function of the capless family members must be unique. A representative of the capless subfamily, PSPTO{_}2114, from the plant pathogenmore » Pseudomonas syringae, was targeted for catalytic activity and structure analyses. The X-ray structure of PSPTO{_}2114 reveals a capless homodimer that conserves some but not all of the intersubunit contacts contributed by the core domains of the phosphonatase homodimer. The region of the PSPTO{_}2114 that corresponds to the catalytic scaffold of phosphonatase (and other HAD phosphotransfereases) positions amino acid residues that are ill suited for Mg+2 cofactor binding and mediation of phosphoryl group transfer between donor and acceptor substrates. The absence of phosphotransferase activity in PSPTO{_}2114 was confirmed by kinetic assays. To explore PSPTO{_}2114 function, the conservation of sequence motifs extending outside of the HADSF catalytic scaffold was examined. The stringently conserved residues among PSPTO{_}2114 homologs were mapped onto the PSPTO{_}2114 three-dimensional structure to identify a surface region unique to the family members that do not possess a cap domain. The hypothesis that this region is used in protein-protein recognition is explored to define, for the first time, HADSF proteins which have acquired a function other than that of a catalyst. Proteins 2008.« less

AU-FREDI - AUTONOMOUS FREQUENCY DOMAIN IDENTIFICATION

NASA Technical Reports Server (NTRS)

Yam, Y.

1994-01-01

The Autonomous Frequency Domain Identification program, AU-FREDI, is a system of methods, algorithms and software that was developed for the identification of structural dynamic parameters and system transfer function characterization for control of large space platforms and flexible spacecraft. It was validated in the CALTECH/Jet Propulsion Laboratory's Large Spacecraft Control Laboratory. Due to the unique characteristics of this laboratory environment, and the environment-specific nature of many of the software's routines, AU-FREDI should be considered to be a collection of routines which can be modified and reassembled to suit system identification and control experiments on large flexible structures. The AU-FREDI software was originally designed to command plant excitation and handle subsequent input/output data transfer, and to conduct system identification based on the I/O data. Key features of the AU-FREDI methodology are as follows: 1. AU-FREDI has on-line digital filter design to support on-orbit optimal input design and data composition. 2. Data composition of experimental data in overlapping frequency bands overcomes finite actuator power constraints. 3. Recursive least squares sine-dwell estimation accurately handles digitized sinusoids and low frequency modes. 4. The system also includes automated estimation of model order using a product moment matrix. 5. A sample-data transfer function parametrization supports digital control design. 6. Minimum variance estimation is assured with a curve fitting algorithm with iterative reweighting. 7. Robust root solvers accurately factorize high order polynomials to determine frequency and damping estimates. 8. Output error characterization of model additive uncertainty supports robustness analysis. The research objectives associated with AU-FREDI were particularly useful in focusing the identification methodology for realistic on-orbit testing conditions. Rather than estimating the entire structure, as is typically done in ground structural testing, AU-FREDI identifies only the key transfer function parameters and uncertainty bounds that are necessary for on-line design and tuning of robust controllers. AU-FREDI's system identification algorithms are independent of the JPL-LSCL environment, and can easily be extracted and modified for use with input/output data files. The basic approach of AU-FREDI's system identification algorithms is to non-parametrically identify the sampled data in the frequency domain using either stochastic or sine-dwell input, and then to obtain a parametric model of the transfer function by curve-fitting techniques. A cross-spectral analysis of the output error is used to determine the additive uncertainty in the estimated transfer function. The nominal transfer function estimate and the estimate of the associated additive uncertainty can be used for robust control analysis and design. AU-FREDI's I/O data transfer routines are tailored to the environment of the CALTECH/ JPL-LSCL which included a special operating system to interface with the testbed. Input commands for a particular experiment (wideband, narrowband, or sine-dwell) were computed on-line and then issued to respective actuators by the operating system. The operating system also took measurements through displacement sensors and passed them back to the software for storage and off-line processing. In order to make use of AU-FREDI's I/O data transfer routines, a user would need to provide an operating system capable of overseeing such functions between the software and the experimental setup at hand. The program documentation contains information designed to support users in either providing such an operating system or modifying the system identification algorithms for use with input/output data files. It provides a history of the theoretical, algorithmic and software development efforts including operating system requirements and listings of some of the various special purpose subroutines which were developed and optimized for Lahey FORTRAN compilers on IBM PC-AT computers before the subroutines were integrated into the system software. Potential purchasers are encouraged to purchase and review the documentation before purchasing the AU-FREDI software. AU-FREDI is distributed in DEC VAX BACKUP format on a 1600 BPI 9-track magnetic tape (standard media) or a TK50 tape cartridge. AU-FREDI was developed in 1989 and is a copyrighted work with all copyright vested in NASA.

Enhancements to the SSME transfer function modeling code

NASA Technical Reports Server (NTRS)

Irwin, R. Dennis; Mitchell, Jerrel R.; Bartholomew, David L.; Glenn, Russell D.

1995-01-01

This report details the results of a one year effort by Ohio University to apply the transfer function modeling and analysis tools developed under NASA Grant NAG8-167 (Irwin, 1992), (Bartholomew, 1992) to attempt the generation of Space Shuttle Main Engine High Pressure Turbopump transfer functions from time domain data. In addition, new enhancements to the transfer function modeling codes which enhance the code functionality are presented, along with some ideas for improved modeling methods and future work. Section 2 contains a review of the analytical background used to generate transfer functions with the SSME transfer function modeling software. Section 2.1 presents the 'ratio method' developed for obtaining models of systems that are subject to single unmeasured excitation sources and have two or more measured output signals. Since most of the models developed during the investigation use the Eigensystem Realization Algorithm (ERA) for model generation, Section 2.2 presents an introduction of ERA, and Section 2.3 describes how it can be used to model spectral quantities. Section 2.4 details the Residue Identification Algorithm (RID) including the use of Constrained Least Squares (CLS) and Total Least Squares (TLS). Most of this information can be found in the report (and is repeated for convenience). Section 3 chronicles the effort of applying the SSME transfer function modeling codes to the a51p394.dat and a51p1294.dat time data files to generate transfer functions from the unmeasured input to the 129.4 degree sensor output. Included are transfer function modeling attempts using five methods. The first method is a direct application of the SSME codes to the data files and the second method uses the underlying trends in the spectral density estimates to form transfer function models with less clustering of poles and zeros than the models obtained by the direct method. In the third approach, the time data is low pass filtered prior to the modeling process in an effort to filter out high frequency characteristics. The fourth method removes the presumed system excitation and its harmonics in order to investigate the effects of the excitation on the modeling process. The fifth method is an attempt to apply constrained RID to obtain better transfer functions through more accurate modeling over certain frequency ranges. Section 4 presents some new C main files which were created to round out the functionality of the existing SSME transfer function modeling code. It is now possible to go from time data to transfer function models using only the C codes; it is not necessary to rely on external software. The new C main files and instructions for their use are included. Section 5 presents current and future enhancements to the XPLOT graphics program which was delivered with the initial software. Several new features which have been added to the program are detailed in the first part of this section. The remainder of Section 5 then lists some possible features which may be added in the future. Section 6 contains the conclusion section of this report. Section 6.1 is an overview of the work including a summary and observations relating to finding transfer functions with the SSME code. Section 6.2 contains information relating to future work on the project.

Punch stretching process monitoring using acoustic emission signal analysis. II - Application of frequency domain deconvolution

NASA Technical Reports Server (NTRS)

Liang, Steven Y.; Dornfeld, David A.; Nickerson, Jackson A.

1987-01-01

The coloring effect on the acoustic emission signal due to the frequency response of the data acquisition/processing instrumentation may bias the interpretation of AE signal characteristics. In this paper, a frequency domain deconvolution technique, which involves the identification of the instrumentation transfer functions and multiplication of the AE signal spectrum by the inverse of these system functions, has been carried out. In this way, the change in AE signal characteristics can be better interpreted as the result of the change in only the states of the process. Punch stretching process was used as an example to demonstrate the application of the technique. Results showed that, through the deconvolution, the frequency characteristics of AE signals generated during the stretching became more distinctive and can be more effectively used as tools for process monitoring.

Transfer functions for protein signal transduction: application to a model of striatal neural plasticity.

PubMed

Scheler, Gabriele

2013-01-01

We present a novel formulation for biochemical reaction networks in the context of protein signal transduction. The model consists of input-output transfer functions, which are derived from differential equations, using stable equilibria. We select a set of "source" species, which are interpreted as input signals. Signals are transmitted to all other species in the system (the "target" species) with a specific delay and with a specific transmission strength. The delay is computed as the maximal reaction time until a stable equilibrium for the target species is reached, in the context of all other reactions in the system. The transmission strength is the concentration change of the target species. The computed input-output transfer functions can be stored in a matrix, fitted with parameters, and even recalled to build dynamical models on the basis of state changes. By separating the temporal and the magnitudinal domain we can greatly simplify the computational model, circumventing typical problems of complex dynamical systems. The transfer function transformation of biochemical reaction systems can be applied to mass-action kinetic models of signal transduction. The paper shows that this approach yields significant novel insights while remaining a fully testable and executable dynamical model for signal transduction. In particular we can deconstruct the complex system into local transfer functions between individual species. As an example, we examine modularity and signal integration using a published model of striatal neural plasticity. The modularizations that emerge correspond to a known biological distinction between calcium-dependent and cAMP-dependent pathways. Remarkably, we found that overall interconnectedness depends on the magnitude of inputs, with higher connectivity at low input concentrations and significant modularization at moderate to high input concentrations. This general result, which directly follows from the properties of individual transfer functions, contradicts notions of ubiquitous complexity by showing input-dependent signal transmission inactivation.

D Semantic Labeling of ALS Data Based on Domain Adaption by Transferring and Fusing Random Forest Models

NASA Astrophysics Data System (ADS)

Wu, J.; Yao, W.; Zhang, J.; Li, Y.

2018-04-01

Labeling 3D point cloud data with traditional supervised learning methods requires considerable labelled samples, the collection of which is cost and time expensive. This work focuses on adopting domain adaption concept to transfer existing trained random forest classifiers (based on source domain) to new data scenes (target domain), which aims at reducing the dependence of accurate 3D semantic labeling in point clouds on training samples from the new data scene. Firstly, two random forest classifiers were firstly trained with existing samples previously collected for other data. They were different from each other by using two different decision tree construction algorithms: C4.5 with information gain ratio and CART with Gini index. Secondly, four random forest classifiers adapted to the target domain are derived through transferring each tree in the source random forest models with two types of operations: structure expansion and reduction-SER and structure transfer-STRUT. Finally, points in target domain are labelled by fusing the four newly derived random forest classifiers using weights of evidence based fusion model. To validate our method, experimental analysis was conducted using 3 datasets: one is used as the source domain data (Vaihingen data for 3D Semantic Labelling); another two are used as the target domain data from two cities in China (Jinmen city and Dunhuang city). Overall accuracies of 85.5 % and 83.3 % for 3D labelling were achieved for Jinmen city and Dunhuang city data respectively, with only 1/3 newly labelled samples compared to the cases without domain adaption.

Structural insights into RNA processing by the human RISC-loading complex.

PubMed

Wang, Hong-Wei; Noland, Cameron; Siridechadilok, Bunpote; Taylor, David W; Ma, Enbo; Felderer, Karin; Doudna, Jennifer A; Nogales, Eva

2009-11-01

Targeted gene silencing by RNA interference (RNAi) requires loading of a short guide RNA (small interfering RNA (siRNA) or microRNA (miRNA)) onto an Argonaute protein to form the functional center of an RNA-induced silencing complex (RISC). In humans, Argonaute2 (AGO2) assembles with the guide RNA-generating enzyme Dicer and the RNA-binding protein TRBP to form a RISC-loading complex (RLC), which is necessary for efficient transfer of nascent siRNAs and miRNAs from Dicer to AGO2. Here, using single-particle EM analysis, we show that human Dicer has an L-shaped structure. The RLC Dicer's N-terminal DExH/D domain, located in a short 'base branch', interacts with TRBP, whereas its C-terminal catalytic domains in the main body are proximal to AGO2. A model generated by docking the available atomic structures of Dicer and Argonaute homologs into the RLC reconstruction suggests a mechanism for siRNA transfer from Dicer to AGO2.

Covalent Linking Greatly Enhances Photoinduced Electron Transfer in Fullerene-Quantum Dot Nanocomposites: Time-Domain Ab Initio Study.

PubMed

Chaban, Vitaly V; Prezhdo, Victor V; Prezhdo, Oleg V

2013-01-03

Nonadiabatic molecular dynamics combined with time-domain density functional theory are used to study electron transfer (ET) from a CdSe quantum dot (QD) to the C60 fullerene, occurring in several types of hybrid organic/inorganic nanocomposites. By unveiling the time dependence of the ET process, we show that covalent bonding between the QD and C60 is particularly important to ensure ultrafast transmission of the excited electron from the QD photon-harvester to the C60 electron acceptor. Despite the close proximity of the donor and acceptor species provided by direct van der Waals contact, it leads to a notably weaker QD-C60 interaction than a lengthy molecular bridge. We show that the ET rate in a nonbonded mixture of QDs and C60 can be enhanced by doping. The photoinduced ET is promoted primarily by mid- and low-frequency vibrations. The study establishes the basic design principles for enhancing photoinduced charge separation in nanoscale light harvesting materials.

Domain Adaptation with Conditional Transferable Components

PubMed Central

Gong, Mingming; Zhang, Kun; Liu, Tongliang; Tao, Dacheng; Glymour, Clark; Schölkopf, Bernhard

2017-01-01

Domain adaptation arises in supervised learning when the training (source domain) and test (target domain) data have different distributions. Let X and Y denote the features and target, respectively, previous work on domain adaptation mainly considers the covariate shift situation where the distribution of the features P(X) changes across domains while the conditional distribution P(Y∣X) stays the same. To reduce domain discrepancy, recent methods try to find invariant components T(X) that have similar P(T(X)) on different domains by explicitly minimizing a distribution discrepancy measure. However, it is not clear if P(Y∣T(X)) in different domains is also similar when P(Y∣X) changes. Furthermore, transferable components do not necessarily have to be invariant. If the change in some components is identifiable, we can make use of such components for prediction in the target domain. In this paper, we focus on the case where P(X∣Y) and P(Y) both change in a causal system in which Y is the cause for X. Under appropriate assumptions, we aim to extract conditional transferable components whose conditional distribution P(T(X)∣Y) is invariant after proper location-scale (LS) transformations, and identify how P(Y) changes between domains simultaneously. We provide theoretical analysis and empirical evaluation on both synthetic and real-world data to show the effectiveness of our method. PMID:28239433

Unsupervised Transfer Learning via Multi-Scale Convolutional Sparse Coding for Biomedical Applications

PubMed Central

Chang, Hang; Han, Ju; Zhong, Cheng; Snijders, Antoine M.; Mao, Jian-Hua

2017-01-01

The capabilities of (I) learning transferable knowledge across domains; and (II) fine-tuning the pre-learned base knowledge towards tasks with considerably smaller data scale are extremely important. Many of the existing transfer learning techniques are supervised approaches, among which deep learning has the demonstrated power of learning domain transferrable knowledge with large scale network trained on massive amounts of labeled data. However, in many biomedical tasks, both the data and the corresponding label can be very limited, where the unsupervised transfer learning capability is urgently needed. In this paper, we proposed a novel multi-scale convolutional sparse coding (MSCSC) method, that (I) automatically learns filter banks at different scales in a joint fashion with enforced scale-specificity of learned patterns; and (II) provides an unsupervised solution for learning transferable base knowledge and fine-tuning it towards target tasks. Extensive experimental evaluation of MSCSC demonstrates the effectiveness of the proposed MSCSC in both regular and transfer learning tasks in various biomedical domains. PMID:28129148

The Data Transfer Kit: A geometric rendezvous-based tool for multiphysics data transfer

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

Slattery, S. R.; Wilson, P. P. H.; Pawlowski, R. P.

2013-07-01

The Data Transfer Kit (DTK) is a software library designed to provide parallel data transfer services for arbitrary physics components based on the concept of geometric rendezvous. The rendezvous algorithm provides a means to geometrically correlate two geometric domains that may be arbitrarily decomposed in a parallel simulation. By repartitioning both domains such that they have the same geometric domain on each parallel process, efficient and load balanced search operations and data transfer can be performed at a desirable algorithmic time complexity with low communication overhead relative to other types of mapping algorithms. With the increased development efforts in multiphysicsmore » simulation and other multiple mesh and geometry problems, generating parallel topology maps for transferring fields and other data between geometric domains is a common operation. The algorithms used to generate parallel topology maps based on the concept of geometric rendezvous as implemented in DTK are described with an example using a conjugate heat transfer calculation and thermal coupling with a neutronics code. In addition, we provide the results of initial scaling studies performed on the Jaguar Cray XK6 system at Oak Ridge National Laboratory for a worse-case-scenario problem in terms of algorithmic complexity that shows good scaling on 0(1 x 104) cores for topology map generation and excellent scaling on 0(1 x 105) cores for the data transfer operation with meshes of O(1 x 109) elements. (authors)« less

Global transformation of erythrocyte properties via engagement of an SH2-like sequence in band 3

PubMed Central

Turrini, Francesco M.; Li, Yen-Hsing; Low, Philip S.

2016-01-01

Src homology 2 (SH2) domains are composed of weakly conserved sequences of ∼100 aa that bind phosphotyrosines in signaling proteins and thereby mediate intra- and intermolecular protein–protein interactions. In exploring the mechanism whereby tyrosine phosphorylation of the erythrocyte anion transporter, band 3, triggers membrane destabilization, vesiculation, and fragmentation, we discovered a SH2 signature motif positioned between membrane-spanning helices 4 and 5. Evidence that this exposed cytoplasmic sequence contributes to a functional SH2-like domain is provided by observations that: (i) it contains the most conserved sequence of SH2 domains, GSFLVR; (ii) it binds the tyrosine phosphorylated cytoplasmic domain of band 3 (cdb3-PO4) with Kd = 14 nM; (iii) binding of cdb3-PO4 to erythrocyte membranes is inhibited both by antibodies against the SH2 signature sequence and dephosphorylation of cdb3-PO4; (iv) label transfer experiments demonstrate the covalent transfer of photoactivatable biotin from isolated cdb3-PO4 (but not cdb3) to band 3 in erythrocyte membranes; and (v) phosphorylation-induced binding of cdb3-PO4 to the membrane-spanning domain of band 3 in intact cells causes global changes in membrane properties, including (i) displacement of a glycolytic enzyme complex from the membrane, (ii) inhibition of anion transport, and (iii) rupture of the band 3–ankyrin bridge connecting the spectrin-based cytoskeleton to the membrane. Because SH2-like motifs are not retrieved by normal homology searches for SH2 domains, but can be found in many tyrosine kinase-regulated transport proteins using modified search programs, we suggest that related cases of membrane transport proteins containing similar motifs are widespread in nature where they participate in regulation of cell properties. PMID:27856737

Multimodal manifold-regularized transfer learning for MCI conversion prediction.

PubMed

Cheng, Bo; Liu, Mingxia; Suk, Heung-Il; Shen, Dinggang; Zhang, Daoqiang

2015-12-01

As the early stage of Alzheimer's disease (AD), mild cognitive impairment (MCI) has high chance to convert to AD. Effective prediction of such conversion from MCI to AD is of great importance for early diagnosis of AD and also for evaluating AD risk pre-symptomatically. Unlike most previous methods that used only the samples from a target domain to train a classifier, in this paper, we propose a novel multimodal manifold-regularized transfer learning (M2TL) method that jointly utilizes samples from another domain (e.g., AD vs. normal controls (NC)) as well as unlabeled samples to boost the performance of the MCI conversion prediction. Specifically, the proposed M2TL method includes two key components. The first one is a kernel-based maximum mean discrepancy criterion, which helps eliminate the potential negative effect induced by the distributional difference between the auxiliary domain (i.e., AD and NC) and the target domain (i.e., MCI converters (MCI-C) and MCI non-converters (MCI-NC)). The second one is a semi-supervised multimodal manifold-regularized least squares classification method, where the target-domain samples, the auxiliary-domain samples, and the unlabeled samples can be jointly used for training our classifier. Furthermore, with the integration of a group sparsity constraint into our objective function, the proposed M2TL has a capability of selecting the informative samples to build a robust classifier. Experimental results on the Alzheimer's Disease Neuroimaging Initiative (ADNI) database validate the effectiveness of the proposed method by significantly improving the classification accuracy of 80.1 % for MCI conversion prediction, and also outperforming the state-of-the-art methods.

Global transformation of erythrocyte properties via engagement of an SH2-like sequence in band 3.

PubMed

Puchulu-Campanella, Estela; Turrini, Francesco M; Li, Yen-Hsing; Low, Philip S

2016-11-29

Src homology 2 (SH2) domains are composed of weakly conserved sequences of ∼100 aa that bind phosphotyrosines in signaling proteins and thereby mediate intra- and intermolecular protein-protein interactions. In exploring the mechanism whereby tyrosine phosphorylation of the erythrocyte anion transporter, band 3, triggers membrane destabilization, vesiculation, and fragmentation, we discovered a SH2 signature motif positioned between membrane-spanning helices 4 and 5. Evidence that this exposed cytoplasmic sequence contributes to a functional SH2-like domain is provided by observations that: (i) it contains the most conserved sequence of SH2 domains, GSFLVR; (ii) it binds the tyrosine phosphorylated cytoplasmic domain of band 3 (cdb3-PO 4 ) with K d = 14 nM; (iii) binding of cdb3-PO 4 to erythrocyte membranes is inhibited both by antibodies against the SH2 signature sequence and dephosphorylation of cdb3-PO 4 ; (iv) label transfer experiments demonstrate the covalent transfer of photoactivatable biotin from isolated cdb3-PO 4 (but not cdb3) to band 3 in erythrocyte membranes; and (v) phosphorylation-induced binding of cdb3-PO 4 to the membrane-spanning domain of band 3 in intact cells causes global changes in membrane properties, including (i) displacement of a glycolytic enzyme complex from the membrane, (ii) inhibition of anion transport, and (iii) rupture of the band 3-ankyrin bridge connecting the spectrin-based cytoskeleton to the membrane. Because SH2-like motifs are not retrieved by normal homology searches for SH2 domains, but can be found in many tyrosine kinase-regulated transport proteins using modified search programs, we suggest that related cases of membrane transport proteins containing similar motifs are widespread in nature where they participate in regulation of cell properties.

Fabrication of functional fibronectin patterns by nanosecond excimer laser direct write for tissue engineering applications.

PubMed

Grigorescu, S; Hindié, M; Axente, E; Carreiras, F; Anselme, K; Werckmann, J; Mihailescu, I N; Gallet, O

2013-07-01

Laser direct write techniques represent a prospective alternative for engineering a new generation of hybrid biomaterials via the creation of patterns consisting of biological proteins onto practically any type of substrate. In this paper we report on the characterization of fibronectin features obtained onto titanium substrates by UV nanosecond laser transfer. Fourier-transform infrared spectroscopy measurements evidenced no modification in the secondary structure of the post-transferred protein. The molecular weight of the transferred protein was identical to the initial fibronectin, no fragment bands being found in the transferred protein's Western blot migration profile. The presence of the cell-binding domain sequence and the mannose groups within the transferred molecules was revealed by anti-fibronectin monoclonal antibody immunolabelling and FITC-Concanavalin-A staining, respectively. The in vitro tests performed with MC3T3-E1 osteoblast-like cells and Swiss-3T3 fibroblasts showed that the cells' morphology and spreading were strongly influenced by the presence of the fibronectin spots.

Distinct Domains of CheA Confer Unique Functions in Chemotaxis and Cell Length in Azospirillum brasilense Sp7.

PubMed

Gullett, Jessica M; Bible, Amber; Alexandre, Gladys

2017-07-01

Chemotaxis is the movement of cells in response to gradients of diverse chemical cues. Motile bacteria utilize a conserved chemotaxis signal transduction system to bias their motility and navigate through a gradient. A central regulator of chemotaxis is the histidine kinase CheA. This cytoplasmic protein interacts with membrane-bound receptors, which assemble into large polar arrays, to propagate the signal. In the alphaproteobacterium Azospirillum brasilense , Che1 controls transient increases in swimming speed during chemotaxis, but it also biases the cell length at division. However, the exact underlying molecular mechanisms for Che1-dependent control of multiple cellular behaviors are not known. Here, we identify specific domains of the CheA1 histidine kinase implicated in modulating each of these functions. We show that CheA1 is produced in two isoforms: a membrane-anchored isoform produced as a fusion with a conserved seven-transmembrane domain of unknown function (TMX) at the N terminus and a soluble isoform similar to prototypical CheA. Site-directed and deletion mutagenesis combined with behavioral assays confirm the role of CheA1 in chemotaxis and implicate the TMX domain in mediating changes in cell length. Fluorescence microscopy further reveals that the membrane-anchored isoform is distributed around the cell surface while the soluble isoform localizes at the cell poles. Together, the data provide a mechanism for the role of Che1 in controlling multiple unrelated cellular behaviors via acquisition of a new domain in CheA1 and production of distinct functional isoforms. IMPORTANCE Chemotaxis provides a significant competitive advantage to bacteria in the environment, and this function has been transferred laterally multiple times, with evidence of functional divergence in different genomic contexts. The molecular principles that underlie functional diversification of chemotaxis in various genomic contexts are unknown. Here, we provide a molecular mechanism by which a single CheA protein controls two unrelated functions: chemotaxis and cell length. Acquisition of this multifunctionality is seemingly a recent evolutionary event. The findings illustrate a mechanism by which chemotaxis function may be co-opted to regulate additional cellular functions. Copyright © 2017 American Society for Microbiology.

Distinct Domains of CheA Confer Unique Functions in Chemotaxis and Cell Length in Azospirillum brasilense Sp7

PubMed Central

Gullett, Jessica M.

2017-01-01

ABSTRACT Chemotaxis is the movement of cells in response to gradients of diverse chemical cues. Motile bacteria utilize a conserved chemotaxis signal transduction system to bias their motility and navigate through a gradient. A central regulator of chemotaxis is the histidine kinase CheA. This cytoplasmic protein interacts with membrane-bound receptors, which assemble into large polar arrays, to propagate the signal. In the alphaproteobacterium Azospirillum brasilense, Che1 controls transient increases in swimming speed during chemotaxis, but it also biases the cell length at division. However, the exact underlying molecular mechanisms for Che1-dependent control of multiple cellular behaviors are not known. Here, we identify specific domains of the CheA1 histidine kinase implicated in modulating each of these functions. We show that CheA1 is produced in two isoforms: a membrane-anchored isoform produced as a fusion with a conserved seven-transmembrane domain of unknown function (TMX) at the N terminus and a soluble isoform similar to prototypical CheA. Site-directed and deletion mutagenesis combined with behavioral assays confirm the role of CheA1 in chemotaxis and implicate the TMX domain in mediating changes in cell length. Fluorescence microscopy further reveals that the membrane-anchored isoform is distributed around the cell surface while the soluble isoform localizes at the cell poles. Together, the data provide a mechanism for the role of Che1 in controlling multiple unrelated cellular behaviors via acquisition of a new domain in CheA1 and production of distinct functional isoforms. IMPORTANCE Chemotaxis provides a significant competitive advantage to bacteria in the environment, and this function has been transferred laterally multiple times, with evidence of functional divergence in different genomic contexts. The molecular principles that underlie functional diversification of chemotaxis in various genomic contexts are unknown. Here, we provide a molecular mechanism by which a single CheA protein controls two unrelated functions: chemotaxis and cell length. Acquisition of this multifunctionality is seemingly a recent evolutionary event. The findings illustrate a mechanism by which chemotaxis function may be co-opted to regulate additional cellular functions. PMID:28416707

Contextual memory and skill transfer in category search.

PubMed

Kole, James A; Healy, Alice F; Fierman, Deanna M; Bourne, Lyle E

2010-01-01

In three experiments, we examined transfer and contextual memory in a category search task. Each experiment included two phases (training and test), during which participants searched through category and exemplar menus for targets. In Experiment 1, the targets were from one of two domains during training (grocery store or department store); the domain was either the same or changed at test. Also, the categories were organized in one of two ways (alphabetically or semantically); the organization either remained the same or changed at test. In Experiments 2 and 3, domain and organization were held constant; however, categories or exemplars were the same, partially replaced, or entirely replaced across phases in order to simulate the dynamic nature of category search in everyday situations. Transfer occurred at test when the category organization or domain was maintained and when the categories or exemplars matched (partially or entirely) those at training. These results demonstrate that transfer is facilitated by overlap in training and testing contexts.

Time Domain and Frequency Domain Deterministic Channel Modeling for Tunnel/Mining Environments.

PubMed

Zhou, Chenming; Jacksha, Ronald; Yan, Lincan; Reyes, Miguel; Kovalchik, Peter

2017-01-01

Understanding wireless channels in complex mining environments is critical for designing optimized wireless systems operated in these environments. In this paper, we propose two physics-based, deterministic ultra-wideband (UWB) channel models for characterizing wireless channels in mining/tunnel environments - one in the time domain and the other in the frequency domain. For the time domain model, a general Channel Impulse Response (CIR) is derived and the result is expressed in the classic UWB tapped delay line model. The derived time domain channel model takes into account major propagation controlling factors including tunnel or entry dimensions, frequency, polarization, electrical properties of the four tunnel walls, and transmitter and receiver locations. For the frequency domain model, a complex channel transfer function is derived analytically. Based on the proposed physics-based deterministic channel models, channel parameters such as delay spread, multipath component number, and angular spread are analyzed. It is found that, despite the presence of heavy multipath, both channel delay spread and angular spread for tunnel environments are relatively smaller compared to that of typical indoor environments. The results and findings in this paper have application in the design and deployment of wireless systems in underground mining environments.

Time Domain and Frequency Domain Deterministic Channel Modeling for Tunnel/Mining Environments

PubMed Central

Zhou, Chenming; Jacksha, Ronald; Yan, Lincan; Reyes, Miguel; Kovalchik, Peter

2018-01-01

Understanding wireless channels in complex mining environments is critical for designing optimized wireless systems operated in these environments. In this paper, we propose two physics-based, deterministic ultra-wideband (UWB) channel models for characterizing wireless channels in mining/tunnel environments — one in the time domain and the other in the frequency domain. For the time domain model, a general Channel Impulse Response (CIR) is derived and the result is expressed in the classic UWB tapped delay line model. The derived time domain channel model takes into account major propagation controlling factors including tunnel or entry dimensions, frequency, polarization, electrical properties of the four tunnel walls, and transmitter and receiver locations. For the frequency domain model, a complex channel transfer function is derived analytically. Based on the proposed physics-based deterministic channel models, channel parameters such as delay spread, multipath component number, and angular spread are analyzed. It is found that, despite the presence of heavy multipath, both channel delay spread and angular spread for tunnel environments are relatively smaller compared to that of typical indoor environments. The results and findings in this paper have application in the design and deployment of wireless systems in underground mining environments.† PMID:29457801

Optimized Signaling Method for High-Speed Transmission Channels with Higher Order Transfer Function

NASA Astrophysics Data System (ADS)

Ševčík, Břetislav; Brančík, Lubomír; Kubíček, Michal

2017-08-01

In this paper, the selected results from testing of optimized CMOS friendly signaling method for high-speed communications over cables and printed circuit boards (PCBs) are presented and discussed. The proposed signaling scheme uses modified concept of pulse width modulated (PWM) signal which enables to better equalize significant channel losses during data high-speed transmission. Thus, the very effective signaling method to overcome losses in transmission channels with higher order transfer function, typical for long cables and multilayer PCBs, is clearly analyzed in the time and frequency domain. Experimental results of the measurements include the performance comparison of conventional PWM scheme and clearly show the great potential of the modified signaling method for use in low power CMOS friendly equalization circuits, commonly considered in modern communication standards as PCI-Express, SATA or in Multi-gigabit SerDes interconnects.

Selective Listening Point Audio Based on Blind Signal Separation and Stereophonic Technology

NASA Astrophysics Data System (ADS)

Niwa, Kenta; Nishino, Takanori; Takeda, Kazuya

A sound field reproduction method is proposed that uses blind source separation and a head-related transfer function. In the proposed system, multichannel acoustic signals captured at distant microphones are decomposed to a set of location/signal pairs of virtual sound sources based on frequency-domain independent component analysis. After estimating the locations and the signals of the virtual sources by convolving the controlled acoustic transfer functions with each signal, the spatial sound is constructed at the selected point. In experiments, a sound field made by six sound sources is captured using 48 distant microphones and decomposed into sets of virtual sound sources. Since subjective evaluation shows no significant difference between natural and reconstructed sound when six virtual sources and are used, the effectiveness of the decomposing algorithm as well as the virtual source representation are confirmed.

Optical properties reconstruction using the adjoint method based on the radiative transfer equation

NASA Astrophysics Data System (ADS)

Addoum, Ahmad; Farges, Olivier; Asllanaj, Fatmir

2018-01-01

An efficient algorithm is proposed to reconstruct the spatial distribution of optical properties in heterogeneous media like biological tissues. The light transport through such media is accurately described by the radiative transfer equation in the frequency-domain. The adjoint method is used to efficiently compute the objective function gradient with respect to optical parameters. Numerical tests show that the algorithm is accurate and robust to retrieve simultaneously the absorption μa and scattering μs coefficients for lowly and highly absorbing medium. Moreover, the simultaneous reconstruction of μs and the anisotropy factor g of the Henyey-Greenstein phase function is achieved with a reasonable accuracy. The main novelty in this work is the reconstruction of g which might open the possibility to image this parameter in tissues as an additional contrast agent in optical tomography.

Geoelectrical inference of mass transfer parameters using temporal moments

USGS Publications Warehouse

Day-Lewis, Frederick D.; Singha, Kamini

2008-01-01

We present an approach to infer mass transfer parameters based on (1) an analytical model that relates the temporal moments of mobile and bulk concentration and (2) a bicontinuum modification to Archie's law. Whereas conventional geochemical measurements preferentially sample from the mobile domain, electrical resistivity tomography (ERT) is sensitive to bulk electrical conductivity and, thus, electrolytic solute in both the mobile and immobile domains. We demonstrate the new approach, in which temporal moments of collocated mobile domain conductivity (i.e., conventional sampling) and ERT‐estimated bulk conductivity are used to calculate heterogeneous mass transfer rate and immobile porosity fractions in a series of numerical column experiments.

Applying the Brakes to Multi-Site SR Protein Phosphorylation: Substrate-Induced Effects on the Splicing Kinase SRPK1†

PubMed Central

Aubol, Brandon E.; Adams, Joseph A.

2011-01-01

To investigate how a protein kinase interacts with its protein substrate during extended, multi-site phosphorylation, the kinetic mechanism of a protein kinase involved in mRNA splicing control was investigated using rapid quench flow techniques. The protein kinase SRPK1 phosphorylates approximately 10 serines in the arginine-serine-rich domain (RS domain) of the SR protein SRSF1 in a C-to-N-terminal direction, a modification that directs this essential splicing factor from the cytoplasm to the nucleus. Transient-state kinetic experiments illustrate that the first phosphate is added rapidly onto the RS domain of SRSF1 (t1/2 = 0.1 sec) followed by slower, multi-site phosphorylation at the remaining serines (t1/2 = 15 sec). Mutagenesis experiments suggest that efficient phosphorylation rates are maintained by an extensive hydrogen bonding and electrostatic network between the RS domain of the SR protein and the active site and docking groove of the kinase. Catalytic trapping and viscosometric experiments demonstrate that while the phosphoryl transfer step is fast, ADP release limits multi-site phosphorylation. By studying phosphate incorporation into selectively pre-phosphorylated forms of the enzyme-substrate complex, the kinetic mechanism for site-specific phosphorylation along the reaction coordinate was assessed. The binding affinity of the SR protein, the phosphoryl transfer rate and ADP exchange rate were found to decline significantly as a function of progressive phosphorylation in the RS domain. These findings indicate that the protein substrate actively modulates initiation, extension and termination events associated with prolonged, multi-site phosphorylation. PMID:21728354

Unfolding the HIV-1 reverse transcriptase RNase H domain – how to lose a molecular tug-of-war

DOE PAGES

Zheng, Xunhai; Pedersen, Lars C.; Gabel, Scott A.; ...

2016-01-14

Formation of the mature HIV-1 reverse transcriptase (RT) p66/p51 heterodimer requires subunit-specific processing of the p66/p66' homodimer precursor. Since the ribonuclease H (RH) domain contains an occult cleavage site located near its center, cleavage must occur either prior to folding or subsequent to unfolding. Recent NMR studies have identified a slow, subunit-specific RH domain unfolding process proposed to result from a residue tug-of-war between the polymerase and RH domains on the functionally inactive, p66' subunit. Here, we describe a structural comparison of the isolated RH domain with a domain swapped RH dimer that reveals several intrinsically destabilizing characteristics of themore » isolated domain that facilitate excursions of Tyr427 from its binding pocket and separation of helices B and D. These studies provide independent support for the subunit-selective RH domain unfolding pathway in which instability of the Tyr427 binding pocket facilitates its release followed by domain transfer, acting as a trigger for further RH domain destabilization and subsequent unfolding. As further support for this pathway, NMR studies demonstrate that addition of an RH active site-directed isoquinolone ligand retards the subunit-selective RH' domain unfolding behavior of the p66/p66' homodimer. As a result, this study demonstrates the feasibility of directly targeting RT maturation with therapeutics.« less

Unfolding the HIV-1 reverse transcriptase RNase H domain – how to lose a molecular tug-of-war

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

Zheng, Xunhai; Pedersen, Lars C.; Gabel, Scott A.

Formation of the mature HIV-1 reverse transcriptase (RT) p66/p51 heterodimer requires subunit-specific processing of the p66/p66' homodimer precursor. Since the ribonuclease H (RH) domain contains an occult cleavage site located near its center, cleavage must occur either prior to folding or subsequent to unfolding. Recent NMR studies have identified a slow, subunit-specific RH domain unfolding process proposed to result from a residue tug-of-war between the polymerase and RH domains on the functionally inactive, p66' subunit. Here, we describe a structural comparison of the isolated RH domain with a domain swapped RH dimer that reveals several intrinsically destabilizing characteristics of themore » isolated domain that facilitate excursions of Tyr427 from its binding pocket and separation of helices B and D. These studies provide independent support for the subunit-selective RH domain unfolding pathway in which instability of the Tyr427 binding pocket facilitates its release followed by domain transfer, acting as a trigger for further RH domain destabilization and subsequent unfolding. As further support for this pathway, NMR studies demonstrate that addition of an RH active site-directed isoquinolone ligand retards the subunit-selective RH' domain unfolding behavior of the p66/p66' homodimer. As a result, this study demonstrates the feasibility of directly targeting RT maturation with therapeutics.« less

Radiative heat transfer in strongly forward scattering media using the discrete ordinates method

NASA Astrophysics Data System (ADS)

Granate, Pedro; Coelho, Pedro J.; Roger, Maxime

2016-03-01

The discrete ordinates method (DOM) is widely used to solve the radiative transfer equation, often yielding satisfactory results. However, in the presence of strongly forward scattering media, this method does not generally conserve the scattering energy and the phase function asymmetry factor. Because of this, the normalization of the phase function has been proposed to guarantee that the scattering energy and the asymmetry factor are conserved. Various authors have used different normalization techniques. Three of these are compared in the present work, along with two other methods, one based on the finite volume method (FVM) and another one based on the spherical harmonics discrete ordinates method (SHDOM). In addition, the approximation of the Henyey-Greenstein phase function by a different one is investigated as an alternative to the phase function normalization. The approximate phase function is given by the sum of a Dirac delta function, which accounts for the forward scattering peak, and a smoother scaled phase function. In this study, these techniques are applied to three scalar radiative transfer test cases, namely a three-dimensional cubic domain with a purely scattering medium, an axisymmetric cylindrical enclosure containing an emitting-absorbing-scattering medium, and a three-dimensional transient problem with collimated irradiation. The present results show that accurate predictions are achieved for strongly forward scattering media when the phase function is normalized in such a way that both the scattered energy and the phase function asymmetry factor are conserved. The normalization of the phase function may be avoided using the FVM or the SHDOM to evaluate the in-scattering term of the radiative transfer equation. Both methods yield results whose accuracy is similar to that obtained using the DOM along with normalization of the phase function. Very satisfactory predictions were also achieved using the delta-M phase function, while the delta-Eddington phase function and the transport approximation may perform poorly.

Extended synaptotagmins are Ca2+-dependent lipid transfer proteins at membrane contact sites.

PubMed

Yu, Haijia; Liu, Yinghui; Gulbranson, Daniel R; Paine, Alex; Rathore, Shailendra S; Shen, Jingshi

2016-04-19

Organelles are in constant communication with each other through exchange of proteins (mediated by trafficking vesicles) and lipids [mediated by both trafficking vesicles and lipid transfer proteins (LTPs)]. It has long been known that vesicle trafficking can be tightly regulated by the second messenger Ca(2+), allowing membrane protein transport to be adjusted according to physiological demands. However, it remains unclear whether LTP-mediated lipid transport can also be regulated by Ca(2+) In this work, we show that extended synaptotagmins (E-Syts), poorly understood membrane proteins at endoplasmic reticulum-plasma membrane contact sites, are Ca(2+)-dependent LTPs. Using both recombinant and endogenous mammalian proteins, we discovered that E-Syts transfer glycerophospholipids between membrane bilayers in the presence of Ca(2+) E-Syts use their lipid-accommodating synaptotagmin-like mitochondrial lipid binding protein (SMP) domains to transfer lipids. However, the SMP domains themselves cannot transport lipids unless the two membranes are tightly tethered by Ca(2+)-bound C2 domains. Strikingly, the Ca(2+)-regulated lipid transfer activity of E-Syts was fully recapitulated when the SMP domain was fused to the cytosolic domain of synaptotagmin-1, the Ca(2+)sensor in synaptic vesicle fusion, indicating that a common mechanism of membrane tethering governs the Ca(2+)regulation of lipid transfer and vesicle fusion. Finally, we showed that microsomal vesicles isolated from mammalian cells contained robust Ca(2+)-dependent lipid transfer activities, which were mediated by E-Syts. These findings established E-Syts as a novel class of LTPs and showed that LTP-mediated lipid trafficking, like vesicular transport, can be subject to tight Ca(2+)regulation.

Interpreting Popov criteria in Lure´ systems with complex scaling stability analysis

NASA Astrophysics Data System (ADS)

Zhou, J.

2018-06-01

The paper presents a novel frequency-domain interpretation of Popov criteria for absolute stability in Lure´ systems by means of what we call complex scaling stability analysis. The complex scaling technique is developed for exponential/asymptotic stability in LTI feedback systems, which dispenses open-loop poles distribution, contour/locus orientation and prior frequency sweeping. Exploiting the technique for alternatively revealing positive realness of transfer functions, re-interpreting Popov criteria is explicated. More specifically, the suggested frequency-domain stability conditions are conformable both in scalar and multivariable cases, and can be implemented either graphically with locus plotting or numerically without; in particular, the latter is suitable as a design tool with auxiliary parameter freedom. The interpretation also reveals further frequency-domain facts about Lure´ systems. Numerical examples are included to illustrate the main results.

Improving the resolution for Lamb wave testing via a smoothed Capon algorithm

NASA Astrophysics Data System (ADS)

Cao, Xuwei; Zeng, Liang; Lin, Jing; Hua, Jiadong

2018-04-01

Lamb wave testing is promising for damage detection and evaluation in large-area structures. The dispersion of Lamb waves is often unavoidable, restricting testing resolution and making the signal hard to interpret. A smoothed Capon algorithm is proposed in this paper to estimate the accurate path length of each wave packet. In the algorithm, frequency domain whitening is firstly used to obtain the transfer function in the bandwidth of the excitation pulse. Subsequently, wavenumber domain smoothing is employed to reduce the correlation between wave packets. Finally, the path lengths are determined by distance domain searching based on the Capon algorithm. Simulations are applied to optimize the number of smoothing times. Experiments are performed on an aluminum plate consisting of two simulated defects. The results demonstrate that spatial resolution is improved significantly by the proposed algorithm.

FRET-based binding assay between a fluorescent cAMP analogue and a cyclic nucleotide-binding domain tagged with a CFP.

PubMed

Romero, Francisco; Santana-Calvo, Carmen; Sánchez-Guevara, Yoloxochitl; Nishigaki, Takuya

2017-09-01

The cyclic nucleotide-binding domain (CNBD) functions as a regulatory domain of many proteins involved in cyclic nucleotide signalling. We developed a straightforward and reliable binding assay based on intermolecular fluorescence resonance energy transfer (FRET) between an adenosine-3', 5'-cyclic monophosphate analogue labelled with fluorescein and a recombinant CNBD of human EPAC1 tagged with a cyan fluorescence protein (CFP). The high FRET efficiency of this method (~ 80%) allowed us to perform several types of binding experiments with nanomolar range of sample using conventional equipment. In addition, the CFP tag on the CNBD enabled us to perform a specific binding experiment using an unpurified protein. Considering these advantages, this technique is useful to study poorly characterized CNBDs. © 2017 Federation of European Biochemical Societies.

The heat-transfer method: a versatile low-cost, label-free, fast, and user-friendly readout platform for biosensor applications.

PubMed

van Grinsven, Bart; Eersels, Kasper; Peeters, Marloes; Losada-Pérez, Patricia; Vandenryt, Thijs; Cleij, Thomas J; Wagner, Patrick

2014-08-27

In recent years, biosensors have become increasingly important in various scientific domains including medicine, biology, and pharmacology, resulting in an increased demand for fast and effective readout techniques. In this Spotlight on Applications, we report on the recently developed heat-transfer method (HTM) and illustrate the use of the technique by zooming in on four established bio(mimetic) sensor applications: (i) mutation analysis in DNA sequences, (ii) cancer cell identification through surface-imprinted polymers, (iii) detection of neurotransmitters with molecularly imprinted polymers, and (iv) phase-transition analysis in lipid vesicle layers. The methodology is based on changes in heat-transfer resistance at a functionalized solid-liquid interface. To this extent, the device applies a temperature gradient over this interface and monitors the temperature underneath and above the functionalized chip in time. The heat-transfer resistance can be obtained by dividing this temperature gradient by the power needed to achieve a programmed temperature. The low-cost, fast, label-free and user-friendly nature of the technology in combination with a high degree of specificity, selectivity, and sensitivity makes HTM a promising sensor technology.

Relationship between CYP1A2 Localization and Lipid Microdomain Formation as a Function of Lipid Composition

PubMed Central

Brignac-Huber, Lauren M.; Reed, James R.; Eyer, Marilyn K.

2013-01-01

Cytochrome P450 (P450) function requires the interaction of P450 and NADPH-cytochrome P450 reductase (CPR) in membranes, and is frequently studied using reconstituted systems composed solely of phosphatidylcholine. There is increasing evidence that other endoplasmic reticulum (ER) lipids can affect P450 structure, activity, and interactions with CPR. Some of these lipid effects have been attributed to the formation of organized liquid-ordered (lo) domains. The goal of this study was to determine if lo domains were formed in P450 reconstituted systems mimicking the ER membrane. CYP1A2, when incorporated in “ER-like” lipid vesicles, displayed detergent insolubility after treatment with Brij 98 and centrifugation in a sucrose gradient. Lipid probes were employed to identify domain formation in both ER-like vesicles and model membranes known to form lo domains. Changes in fluorescence resonance energy transfer (FRET) using an established donor/acceptor FRET pair in both ER-like and model lo-forming systems demonstrated the coexistence of lo- and liquid-disordered domains as a function of cholesterol and sphingomyelin content. Similarly, 6-dodecanoyl-2-dimethylaminonaphthalene (laurdan), a probe that reports on membrane organization, showed that cholesterol and sphingomyelin increased membrane order. Finally, brominated-phosphatidylcholine allowed for monitoring of the location of both CPR and CYP1A2 within the lo regions of ER-like systems. Taken together, the results demonstrate that ER-like vesicles generate microdomains, and both CYP1A2 and CPR predominantly localize into lo membrane regions. Probe fluorescent responses suggest that lipid microdomains form in these vesicles whether or not enzymes are included in the reconstituted systems. Thus, it does not appear that the proteins are critical for stabilizing lo domains. PMID:23963955

The prokaryotic antecedents of the ubiquitin-signaling system and the early evolution of ubiquitin-like β-grasp domains

PubMed Central

Iyer, Lakshminarayan M; Burroughs, A Maxwell; Aravind, L

2006-01-01

Background Ubiquitin (Ub)-mediated signaling is one of the hallmarks of all eukaryotes. Prokaryotic homologs of Ub (ThiS and MoaD) and E1 ligases have been studied in relation to sulfur incorporation reactions in thiamine and molybdenum/tungsten cofactor biosynthesis. However, there is no evidence for entire protein modification systems with Ub-like proteins and deconjugation by deubiquitinating enzymes in prokaryotes. Hence, the evolutionary assembly of the eukaryotic Ub-signaling apparatus remains unclear. Results We systematically analyzed prokaryotic Ub-related β-grasp fold proteins using sensitive sequence profile searches and structural analysis. Consequently, we identified novel Ub-related proteins beyond the characterized ThiS, MoaD, TGS, and YukD domains. To understand their functional associations, we sought and recovered several conserved gene neighborhoods and domain architectures. These included novel associations involving diverse sulfur metabolism proteins, siderophore biosynthesis and the gene encoding the transfer mRNA binding protein SmpB, as well as domain fusions between Ub-like domains and PIN-domain related RNAses. Most strikingly, we found conserved gene neighborhoods in phylogenetically diverse bacteria combining genes for JAB domains (the primary de-ubiquitinating isopeptidases of the proteasomal complex), along with E1-like adenylating enzymes and different Ub-related proteins. Further sequence analysis of other conserved genes in these neighborhoods revealed several Ub-conjugating enzyme/E2-ligase related proteins. Genes for an Ub-like protein and a JAB domain peptidase were also found in the tail assembly gene cluster of certain caudate bacteriophages. Conclusion These observations imply that members of the Ub family had already formed strong functional associations with E1-like proteins, UBC/E2-related proteins, and JAB peptidases in the bacteria. Several of these Ub-like proteins and the associated protein families are likely to function together in signaling systems just as in eukaryotes. PMID:16859499

Transfer learning for visual categorization: a survey.

PubMed

Shao, Ling; Zhu, Fan; Li, Xuelong

2015-05-01

Regular machine learning and data mining techniques study the training data for future inferences under a major assumption that the future data are within the same feature space or have the same distribution as the training data. However, due to the limited availability of human labeled training data, training data that stay in the same feature space or have the same distribution as the future data cannot be guaranteed to be sufficient enough to avoid the over-fitting problem. In real-world applications, apart from data in the target domain, related data in a different domain can also be included to expand the availability of our prior knowledge about the target future data. Transfer learning addresses such cross-domain learning problems by extracting useful information from data in a related domain and transferring them for being used in target tasks. In recent years, with transfer learning being applied to visual categorization, some typical problems, e.g., view divergence in action recognition tasks and concept drifting in image classification tasks, can be efficiently solved. In this paper, we survey state-of-the-art transfer learning algorithms in visual categorization applications, such as object recognition, image classification, and human action recognition.

LRAT-specific domain facilitates vitamin A metabolism by domain swapping in HRASLS3

DOE PAGES

Golczak, Marcin; Sears, Avery E.; Kiser, Philip D.; ...

2014-11-10

Cellular uptake of vitamin A, production of visual chromophore and triglyceride homeostasis in adipocytes depend on two representatives of the vertebrate N1pC/P60 protein family, lecithin:retinol acyltransferase (LRAT) and HRAS-like tumor suppressor 3 (HRASLS3). Both proteins function as lipid-metabolizing enzymes but differ in their substrate preferences and dominant catalytic activity. The mechanism of this catalytic diversity is not understood. In this paper, by using a gain-of-function approach, we identified a specific sequence responsible for the substrate specificity of N1pC/P60 proteins. A 2.2-Å crystal structure of the HRASLS3-LRAT chimeric enzyme in a thioester catalytic intermediate state revealed a major structural rearrangement accompaniedmore » by three-dimensional domain swapping dimerization not observed in native HRASLS proteins. Structural changes affecting the active site environment contributed to slower hydrolysis of the catalytic intermediate, supporting efficient acyl transfer. Finally, these findings reveal structural adaptation that facilitates selective catalysis and mechanism responsible for diverse substrate specificity within the LRAT-like enzyme family.« less

The dynamic disulphide relay of quiescin sulphydryl oxidase.

PubMed

Alon, Assaf; Grossman, Iris; Gat, Yair; Kodali, Vamsi K; DiMaio, Frank; Mehlman, Tevie; Haran, Gilad; Baker, David; Thorpe, Colin; Fass, Deborah

2012-08-16

Protein stability, assembly, localization and regulation often depend on the formation of disulphide crosslinks between cysteine side chains. Enzymes known as sulphydryl oxidases catalyse de novo disulphide formation and initiate intra- and intermolecular dithiol/disulphide relays to deliver the disulphides to substrate proteins. Quiescin sulphydryl oxidase (QSOX) is a unique, multi-domain disulphide catalyst that is localized primarily to the Golgi apparatus and secreted fluids and has attracted attention owing to its overproduction in tumours. In addition to its physiological importance, QSOX is a mechanistically intriguing enzyme, encompassing functions typically carried out by a series of proteins in other disulphide-formation pathways. How disulphides are relayed through the multiple redox-active sites of QSOX and whether there is a functional benefit to concatenating these sites on a single polypeptide are open questions. Here we present the first crystal structure of an intact QSOX enzyme, derived from a trypanosome parasite. Notably, sequential sites in the disulphide relay were found more than 40 Å apart in this structure, too far for direct disulphide transfer. To resolve this puzzle, we trapped and crystallized an intermediate in the disulphide hand-off, which showed a 165° domain rotation relative to the original structure, bringing the two active sites within disulphide-bonding distance. The comparable structure of a mammalian QSOX enzyme, also presented here, shows further biochemical features that facilitate disulphide transfer in metazoan orthologues. Finally, we quantified the contribution of concatenation to QSOX activity, providing general lessons for the understanding of multi-domain enzymes and the design of new catalytic relays.

A Frequency-Domain Multipath Parameter Estimation and Mitigation Method for BOC-Modulated GNSS Signals

PubMed Central

Sun, Chao; Feng, Wenquan; Du, Songlin

2018-01-01

As multipath is one of the dominating error sources for high accuracy Global Navigation Satellite System (GNSS) applications, multipath mitigation approaches are employed to minimize this hazardous error in receivers. Binary offset carrier modulation (BOC), as a modernized signal structure, is adopted to achieve significant enhancement. However, because of its multi-peak autocorrelation function, conventional multipath mitigation techniques for binary phase shift keying (BPSK) signal would not be optimal. Currently, non-parametric and parametric approaches have been studied specifically aiming at multipath mitigation for BOC signals. Non-parametric techniques, such as Code Correlation Reference Waveforms (CCRW), usually have good feasibility with simple structures, but suffer from low universal applicability for different BOC signals. Parametric approaches can thoroughly eliminate multipath error by estimating multipath parameters. The problems with this category are at the high computation complexity and vulnerability to the noise. To tackle the problem, we present a practical parametric multipath estimation method in the frequency domain for BOC signals. The received signal is transferred to the frequency domain to separate out the multipath channel transfer function for multipath parameter estimation. During this process, we take the operations of segmentation and averaging to reduce both noise effect and computational load. The performance of the proposed method is evaluated and compared with the previous work in three scenarios. Results indicate that the proposed averaging-Fast Fourier Transform (averaging-FFT) method achieves good robustness in severe multipath environments with lower computational load for both low-order and high-order BOC signals. PMID:29495589

Carbohydrate Recognition Specificity of Trans-sialidase Lectin Domain from Trypanosoma congolense

PubMed Central

Waespy, Mario; Gbem, Thaddeus T.; Elenschneider, Leroy; Jeck, André-Philippe; Day, Christopher J.; Hartley-Tassell, Lauren; Bovin, Nicolai; Tiralongo, Joe; Haselhorst, Thomas; Kelm, Sørge

2015-01-01

Fourteen different active Trypanosoma congolense trans-sialidases (TconTS), 11 variants of TconTS1 besides TconTS2, TconTS3 and TconTS4, have been described. Notably, the specific transfer and sialidase activities of these TconTS differ by orders of magnitude. Surprisingly, phylogenetic analysis of the catalytic domains (CD) grouped each of the highly active TconTS together with the less active enzymes. In contrast, when aligning lectin-like domains (LD), the highly active TconTS grouped together, leading to the hypothesis that the LD of TconTS modulates its enzymatic activity. So far, little is known about the function and ligand specificity of these LDs. To explore their carbohydrate-binding potential, glycan array analysis was performed on the LD of TconTS1, TconTS2, TconTS3 and TconTS4. In addition, Saturation Transfer Difference (STD) NMR experiments were done on TconTS2-LD for a more detailed analysis of its lectin activity. Several mannose-containing oligosaccharides, such as mannobiose, mannotriose and higher mannosylated glycans, as well as Gal, GalNAc and LacNAc containing oligosaccharides were confirmed as binding partners of TconTS1-LD and TconTS2-LD. Interestingly, terminal mannose residues are not acceptor substrates for TconTS activity. This indicates a different, yet unknown biological function for TconTS-LD, including specific interactions with oligomannose-containing glycans on glycoproteins and GPI anchors found on the surface of the parasite, including the TconTS itself. Experimental evidence for such a scenario is presented. PMID:26474304

Structure of Atg7 Alone and its Atg8-Bound Forms

NASA Astrophysics Data System (ADS)

Noda, Nobuo

Atg7 is a noncanonical E1 enzyme that activates Atg8 and transfers it to Atg3 (E2 enzyme), thus playing an essential role in conjugating Atg8 with phosphatidylethanolamine and thus in autophagy. Atg7 protomer is comprised of two globular domains, the N-terminal domain (NTD) and the C-terminal domain (CTD), and forms a homodimer through CTD. Atg7-Atg8 complex structures and biochemical analyses revealed that Atg8 is initially recognized by the C-terminal tail of CTD and is then transferred to the adenylation domain in CTD, where Atg8 Gly116 is adenylated and thioester-linked to the catalytic cysteine of Atg7. Atg8 is then transferred to Atg3 bound to the NTD of the opposite protomer within an Atg7 dimer via a trans mechanism.

Recombinant expression, purification, and crystallization of the glutaminyl-tRNA synthetase from Toxoplasma gondii.

PubMed

van Rooyen, Jason M; Hakimi, Mohamed-Ali; Belrhali, Hassan

2015-06-01

Aminoacyl tRNA synthetases play a critical role in protein synthesis by providing precursor transfer-RNA molecules correctly charged with their cognate amino-acids. The essential nature of these enzymes make them attractive targets for designing new drugs against important pathogenic protozoans like Toxoplasma. Because no structural data currently exists for a protozoan glutaminyl-tRNA synthetase (QRS), an understanding of its potential as a drug target and its function in the assembly of the Toxoplasma multi-aminoacyl tRNA (MARS) complex is therefore lacking. Here we describe the optimization of expression and purification conditions that permitted the recovery and crystallization of both domains of the Toxoplasma QRS enzyme from a heterologous Escherichia coli expression system. Expression of full-length QRS was only achieved after the addition of an N-terminal histidine affinity tag and the isolated protein was active on both cellular and in vitro produced Toxoplasma tRNA. Taking advantage of the proteolytic susceptibility of QRS to cleavage into component domains, N-terminal glutathione S-transferase (GST) motif-containing domain fragments were isolated and crystallization conditions discovered. Isolation of the C-terminal catalytic domain was accomplished after subcloning the domain and optimizing expression conditions. Purified catalytic domain survived cryogenic storage and yielded large diffraction-quality crystals over-night after optimization of screening conditions. This work will form the basis of future structural studies into structural-functional relationships of both domains including potential targeted drug-design studies and investigations into the assembly of the Toxoplasma MARS complex. Copyright © 2015 Elsevier Inc. All rights reserved.

Genome-wide identification and characterization of the apple (Malus domestica) HECT ubiquitin-protein ligase family and expression analysis of their responsiveness to abiotic stresses.

PubMed

Xu, Jianing; Xing, Shanshan; Cui, Haoran; Chen, Xuesen; Wang, Xiaoyun

2016-04-01

The ubiquitin-protein ligases (E3s) directly participate in ubiquitin (Ub) transferring to the target proteins in the ubiquitination pathway. The HECT ubiquitin-protein ligase (UPL), one type of E3s, is characterized as containing a conserved HECT domain of approximately 350 amino acids in the C terminus. Some UPLs were found to be involved in trichome development and leaf senescence in Arabidopsis. However, studies on plant UPLs, such as characteristics of the protein structure, predicted functional motifs of the HECT domain, and the regulatory expression of UPLs have all been limited. Here, we present genome-wide identification of the genes encoding UPLs (HECT gene) in apple. The 13 genes (named as MdUPL1-MdUPL13) from ten different chromosomes were divided into four groups by phylogenetic analysis. Among these groups, the encoding genes in the intron-exon structure and the included additional functional domains were quite different. Notably, the F-box domain was first found in MdUPL7 in plant UPLs. The HECT domain in different MdUPL groups also presented different spatial features and three types of conservative motifs were identified. The promoters of each MdUPL member carried multiple stress-response related elements by cis-acting element analysis. Experimental results demonstrated that the expressions of several MdUPLs were quite sensitive to cold-, drought-, and salt-stresses by qRT-PCR assay. The results of this study helped to elucidate the functions of HECT proteins, especially in Rosaceae plants.

Stability of discrete time recurrent neural networks and nonlinear optimization problems.

PubMed

Singh, Jayant; Barabanov, Nikita

2016-02-01

We consider the method of Reduction of Dissipativity Domain to prove global Lyapunov stability of Discrete Time Recurrent Neural Networks. The standard and advanced criteria for Absolute Stability of these essentially nonlinear systems produce rather weak results. The method mentioned above is proved to be more powerful. It involves a multi-step procedure with maximization of special nonconvex functions over polytopes on every step. We derive conditions which guarantee an existence of at most one point of local maximum for such functions over every hyperplane. This nontrivial result is valid for wide range of neuron transfer functions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evolution and Conservation of Plant NLR Functions

PubMed Central

Jacob, Florence; Vernaldi, Saskia; Maekawa, Takaki

2013-01-01

In plants and animals, nucleotide-binding domain and leucine-rich repeats (NLR)-containing proteins play pivotal roles in innate immunity. Despite their similar biological functions and protein architecture, comparative genome-wide analyses of NLRs and genes encoding NLR-like proteins suggest that plant and animal NLRs have independently arisen in evolution. Furthermore, the demonstration of interfamily transfer of plant NLR functions from their original species to phylogenetically distant species implies evolutionary conservation of the underlying immune principle across plant taxonomy. In this review we discuss plant NLR evolution and summarize recent insights into plant NLR-signaling mechanisms, which might constitute evolutionarily conserved NLR-mediated immune mechanisms. PMID:24093022

Generalizing the correlated chromophore domain model of reversible photodegradation to include the effects of an applied electric field

NASA Astrophysics Data System (ADS)

Anderson, Benjamin; Kuzyk, Mark G.

2014-03-01

All observations of photodegradation and self-healing follow the predictions of the correlated chromophore domain model [Ramini et al., Polym. Chem. 4, 4948 (2013), 10.1039/c3py00263b]. In the present work, we generalize the domain model to describe the effects of an electric field by including induced dipole interactions between molecules in a domain by means of a self-consistent field approach. This electric field correction is added to the statistical mechanical model to calculate the distribution of domains that are central to healing. Also included in the model are the dynamics due to the formation of an irreversibly damaged species, which we propose involves damage to the polymer mediated through energy transfer from a dopant molecule after absorbing a photon. As in previous studies, the model with one-dimensional domains best explains all experimental data of the population as a function of time, temperature, intensity, concentration, and now applied electric field. Though the precise nature of a domain is yet to be determined, the fact that only one-dimensional domain models are consistent with observations suggests that they might be made of correlated dye molecules along polymer chains. Furthermore, the voltage-dependent measurements suggest that the largest polarizability axis of the molecules are oriented perpendicular to the chain.

Controlling allosteric networks in proteins

NASA Astrophysics Data System (ADS)

Dokholyan, Nikolay

2013-03-01

We present a novel methodology based on graph theory and discrete molecular dynamics simulations for delineating allosteric pathways in proteins. We use this methodology to uncover the structural mechanisms responsible for coupling of distal sites on proteins and utilize it for allosteric modulation of proteins. We will present examples where inference of allosteric networks and its rewiring allows us to ``rescue'' cystic fibrosis transmembrane conductance regulator (CFTR), a protein associated with fatal genetic disease cystic fibrosis. We also use our methodology to control protein function allosterically. We design a novel protein domain that can be inserted into identified allosteric site of target protein. Using a drug that binds to our domain, we alter the function of the target protein. We successfully tested this methodology in vitro, in living cells and in zebrafish. We further demonstrate transferability of our allosteric modulation methodology to other systems and extend it to become ligh-activatable.

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.

Identification and Characterization of the Pyridomycin Biosynthetic Gene Cluster of Streptomyces pyridomyceticus NRRL B-2517*

PubMed Central

Huang, Tingting; Wang, Yemin; Yin, Jun; Du, Yanhua; Tao, Meifeng; Xu, Jing; Chen, Wenqing; Lin, Shuangjun; Deng, Zixin

2011-01-01

Pyridomycin is a structurally unique antimycobacterial cyclodepsipeptide containing rare 3-(3-pyridyl)-l-alanine and 2-hydroxy-3-methylpent-2-enoic acid moieties. The biosynthetic gene cluster for pyridomycin has been cloned and identified from Streptomyces pyridomyceticus NRRL B-2517. Sequence analysis of a 42.5-kb DNA region revealed 26 putative open reading frames, including two nonribosomal peptide synthetase (NRPS) genes and a polyketide synthase gene. A special feature is the presence of a polyketide synthase-type ketoreductase domain embedded in an NRPS. Furthermore, we showed that PyrA functioned as an NRPS adenylation domain that activates 3-hydroxypicolinic acid and transfers it to a discrete peptidyl carrier protein, PyrU, which functions as a loading module that initiates pyridomycin biosynthesis in vivo and in vitro. PyrA could also activate other aromatic acids, generating three pyridomycin analogues in vivo. PMID:21454714

Millimeter-wave monolithic integrated circuit characterization by a picosecond optoelectronic technique

NASA Astrophysics Data System (ADS)

Hung, Hing-Loi A.; Smith, Thane; Huang, Ho C.; Polak-Dingels, Penny; Webb, Kevin J.

1989-08-01

The characterization of microwave and millimeter-wave monolithic integrated circits (MIMICs) using picosecond pulse-sampling techniques is developed with emphasis on improving broadband coverage and measurement accuracy. GaAs photoconductive swithces are used for signal generation and sampling operations. The measured time-domain response allows the spectral transfer function of the MIMIC to be obtained. This measurement technique is verified by characterization of the frequency response (magnitude and phase) of a reference 50-ohm microstrip line and a two-stage Ka-band MIMIC amplifier. The measured broadband results agree with those obtained from conventional frequency-domain measurements using a network analyzer. The application of this optical technique to on-wafer MIMIC characterization is described.

The Evolution of Two-Component Systems in Bacteria Reveals Different Strategies for Niche Adaptation

PubMed Central

Arkin, Adam

2006-01-01

Two-component systems including histidine protein kinases represent the primary signal transduction paradigm in prokaryotic organisms. To understand how these systems adapt to allow organisms to detect niche-specific signals, we analyzed the phylogenetic distribution of nearly 5,000 histidine protein kinases from 207 sequenced prokaryotic genomes. We found that many genomes carry a large repertoire of recently evolved signaling genes, which may reflect selective pressure to adapt to new environmental conditions. Both lineage-specific gene family expansion and horizontal gene transfer play major roles in the introduction of new histidine kinases into genomes; however, there are differences in how these two evolutionary forces act. Genes imported via horizontal transfer are more likely to retain their original functionality as inferred from a similar complement of signaling domains, while gene family expansion accompanied by domain shuffling appears to be a major source of novel genetic diversity. Family expansion is the dominant source of new histidine kinase genes in the genomes most enriched in signaling proteins, and detailed analysis reveals that divergence in domain structure and changes in expression patterns are hallmarks of recent expansions. Finally, while these two modes of gene acquisition are widespread across bacterial taxa, there are clear species-specific preferences for which mode is used. PMID:17083272

Cross-domain and multi-task transfer learning of deep convolutional neural network for breast cancer diagnosis in digital breast tomosynthesis

NASA Astrophysics Data System (ADS)

Samala, Ravi K.; Chan, Heang-Ping; Hadjiiski, Lubomir; Helvie, Mark A.; Richter, Caleb; Cha, Kenny

2018-02-01

We propose a cross-domain, multi-task transfer learning framework to transfer knowledge learned from non-medical images by a deep convolutional neural network (DCNN) to medical image recognition task while improving the generalization by multi-task learning of auxiliary tasks. A first stage cross-domain transfer learning was initiated from ImageNet trained DCNN to mammography trained DCNN. 19,632 regions-of-interest (ROI) from 2,454 mass lesions were collected from two imaging modalities: digitized-screen film mammography (SFM) and full-field digital mammography (DM), and split into training and test sets. In the multi-task transfer learning, the DCNN learned the mass classification task simultaneously from the training set of SFM and DM. The best transfer network for mammography was selected from three transfer networks with different number of convolutional layers frozen. The performance of single-task and multitask transfer learning on an independent SFM test set in terms of the area under the receiver operating characteristic curve (AUC) was 0.78+/-0.02 and 0.82+/-0.02, respectively. In the second stage cross-domain transfer learning, a set of 12,680 ROIs from 317 mass lesions on DBT were split into validation and independent test sets. We first studied the data requirements for the first stage mammography trained DCNN by varying the mammography training data from 1% to 100% and evaluated its learning on the DBT validation set in inference mode. We found that the entire available mammography set provided the best generalization. The DBT validation set was then used to train only the last four fully connected layers, resulting in an AUC of 0.90+/-0.04 on the independent DBT test set.

Domain-swapped T cell receptors improve the safety of TCR gene therapy

PubMed Central

Bethune, Michael T; Gee, Marvin H; Bunse, Mario; Lee, Mark S; Gschweng, Eric H; Pagadala, Meghana S; Zhou, Jing; Cheng, Donghui; Heath, James R; Kohn, Donald B; Kuhns, Michael S; Uckert, Wolfgang; Baltimore, David

2016-01-01

T cells engineered to express a tumor-specific αβ T cell receptor (TCR) mediate anti-tumor immunity. However, mispairing of the therapeutic αβ chains with endogenous αβ chains reduces therapeutic TCR surface expression and generates self-reactive TCRs. We report a general strategy to prevent TCR mispairing: swapping constant domains between the α and β chains of a therapeutic TCR. When paired, domain-swapped (ds)TCRs assemble with CD3, express on the cell surface, and mediate antigen-specific T cell responses. By contrast, dsTCR chains mispaired with endogenous chains cannot properly assemble with CD3 or signal, preventing autoimmunity. We validate this approach in cell-based assays and in a mouse model of TCR gene transfer-induced graft-versus-host disease. We also validate a related approach whereby replacement of αβ TCR domains with corresponding γδ TCR domains yields a functional TCR that does not mispair. This work enables the design of safer TCR gene therapies for cancer immunotherapy. DOI: http://dx.doi.org/10.7554/eLife.19095.001 PMID:27823582

The cost of concreteness: the effect of nonessential information on analogical transfer.

PubMed

Kaminski, Jennifer A; Sloutsky, Vladimir M; Heckler, Andrew F

2013-03-01

Most theories of analogical transfer focus on similarities between the learning and transfer domains, where transfer is more likely between domains that share common surface features, similar elements, or common interpretations of structure. We suggest that characteristics of the learning instantiation alone can give rise to different levels of transfer. We propose that concreteness of the learning instantiation can hinder analogical transfer of well-defined structured concepts, such as mathematical concepts. We operationalize the term concreteness as the amount of information communicated through a specific instantiation of a concept. The 5 reported experiments with undergraduate students tested the hypothesis by presenting participants with the concept of a commutative mathematical group of order 3. The experiments varied the level of concreteness of the training instantiation and measured transfer of learning to a new instantiation. The results support the hypothesis, demonstrating better transfer from more generic instantiations (i.e., ones that communicate minimal extraneous information) than from more concrete instantiations. Specifically, concreteness was found to create an obstacle to successful structural alignment across domains, whereas generic instantiations led to spontaneous structural alignment. These findings have important implications for the theory of learning and transfer and practical implications for the design of educational material. Although some concreteness may activate prior knowledge and perhaps offer a leg up in the learning process, this benefit may come at the cost of transfer.

Application handbook for a Standardized Control Module (SCM) for DC-DC converters, volume 1

NASA Astrophysics Data System (ADS)

Lee, F. C.; Mahmoud, M. F.; Yu, Y.

1980-04-01

The standardized control module (SCM) was developed for application in the buck, boost and buck/boost DC-DC converters. The SCM used multiple feedback loops to provide improved input line and output load regulation, stable feedback control system, good dynamic transient response and adaptive compensation of the control loop for changes in open loop gain and output filter time constraints. The necessary modeling and analysis tools to aid the design engineer in the application of the SCM to DC-DC Converters were developed. The SCM functional block diagram and the different analysis techniques were examined. The average time domain analysis technique was chosen as the basic analytical tool. The power stage transfer functions were developed for the buck, boost and buck/boost converters. The analog signal and digital signal processor transfer functions were developed for the three DC-DC Converter types using the constant on time, constant off time and constant frequency control laws.

Application handbook for a Standardized Control Module (SCM) for DC-DC converters, volume 1

NASA Technical Reports Server (NTRS)

Lee, F. C.; Mahmoud, M. F.; Yu, Y.

1980-01-01

The standardized control module (SCM) was developed for application in the buck, boost and buck/boost DC-DC converters. The SCM used multiple feedback loops to provide improved input line and output load regulation, stable feedback control system, good dynamic transient response and adaptive compensation of the control loop for changes in open loop gain and output filter time constraints. The necessary modeling and analysis tools to aid the design engineer in the application of the SCM to DC-DC Converters were developed. The SCM functional block diagram and the different analysis techniques were examined. The average time domain analysis technique was chosen as the basic analytical tool. The power stage transfer functions were developed for the buck, boost and buck/boost converters. The analog signal and digital signal processor transfer functions were developed for the three DC-DC Converter types using the constant on time, constant off time and constant frequency control laws.

Domain Adaptation for Pedestrian Detection Based on Prediction Consistency

PubMed Central

Huan-ling, Tang; Zhi-yong, An

2014-01-01

Pedestrian detection is an active area of research in computer vision. It remains a quite challenging problem in many applications where many factors cause a mismatch between source dataset used to train the pedestrian detector and samples in the target scene. In this paper, we propose a novel domain adaptation model for merging plentiful source domain samples with scared target domain samples to create a scene-specific pedestrian detector that performs as well as rich target domain simples are present. Our approach combines the boosting-based learning algorithm with an entropy-based transferability, which is derived from the prediction consistency with the source classifications, to selectively choose the samples showing positive transferability in source domains to the target domain. Experimental results show that our approach can improve the detection rate, especially with the insufficient labeled data in target scene. PMID:25013850

Analytical transmissibility based transfer path analysis for multi-energy-domain systems using four-pole parameter theory

NASA Astrophysics Data System (ADS)

Mashayekhi, Mohammad Jalali; Behdinan, Kamran

2017-10-01

The increasing demand to minimize undesired vibration and noise levels in several high-tech industries has generated a renewed interest in vibration transfer path analysis. Analyzing vibration transfer paths within a system is of crucial importance in designing an effective vibration isolation strategy. Most of the existing vibration transfer path analysis techniques are empirical which are suitable for diagnosis and troubleshooting purpose. The lack of an analytical transfer path analysis to be used in the design stage is the main motivation behind this research. In this paper an analytical transfer path analysis based on the four-pole theory is proposed for multi-energy-domain systems. Bond graph modeling technique which is an effective approach to model multi-energy-domain systems is used to develop the system model. In this paper an electro-mechanical system is used as a benchmark example to elucidate the effectiveness of the proposed technique. An algorithm to obtain the equivalent four-pole representation of a dynamical systems based on the corresponding bond graph model is also presented in this paper.

Stabilization of non-productive conformations underpins rapid electron transfer to electron-transferring flavoprotein.

PubMed

Toogood, Helen S; van Thiel, Adam; Scrutton, Nigel S; Leys, David

2005-08-26

Crystal structures of protein complexes with electron-transferring flavoprotein (ETF) have revealed a dual protein-protein interface with one region serving as anchor while the ETF FAD domain samples available space within the complex. We show that mutation of the conserved Glu-165beta in human ETF leads to drastically modulated rates of interprotein electron transfer with both medium chain acyl-CoA dehydrogenase and dimethylglycine dehydrogenase. The crystal structure of free E165betaA ETF is essentially identical to that of wild-type ETF, but the crystal structure of the E165betaA ETF.medium chain acyl-CoA dehydrogenase complex reveals clear electron density for the FAD domain in a position optimal for fast interprotein electron transfer. Based on our observations, we present a dynamic multistate model for conformational sampling that for the wild-type ETF. medium chain acyl-CoA dehydrogenase complex involves random motion between three distinct positions for the ETF FAD domain. ETF Glu-165beta plays a key role in stabilizing positions incompatible with fast interprotein electron transfer, thus ensuring high rates of complex dissociation.

Unique helicase determinants in the essential conjugative TraI factor from Salmonella enterica serovar Typhimurium plasmid pCU1.

PubMed

McLaughlin, Krystle J; Nash, Rebekah P; Redinbo, Mathew R

2014-09-01

The widespread development of multidrug-resistant bacteria is a major health emergency. Conjugative DNA plasmids, which harbor a wide range of antibiotic resistance genes, also encode the protein factors necessary to orchestrate the propagation of plasmid DNA between bacterial cells through conjugative transfer. Successful conjugative DNA transfer depends on key catalytic components to nick one strand of the duplex DNA plasmid and separate the DNA strands while cell-to-cell transfer occurs. The TraI protein from the conjugative Salmonella plasmid pCU1 fulfills these key catalytic roles, as it contains both single-stranded DNA-nicking relaxase and ATP-dependent helicase domains within a single, 1,078-residue polypeptide. In this work, we unraveled the helicase determinants of Salmonella pCU1 TraI through DNA binding, ATPase, and DNA strand separation assays. TraI binds DNA substrates with high affinity in a manner influenced by nucleic acid length and the presence of a DNA hairpin structure adjacent to the nick site. TraI selectively hydrolyzes ATP, and mutations in conserved helicase motifs eliminate ATPase activity. Surprisingly, the absence of a relatively short (144-residue) domain at the extreme C terminus of the protein severely diminishes ATP-dependent strand separation. Collectively, these data define the helicase motifs of the conjugative factor TraI from Salmonella pCU1 and reveal a previously uncharacterized C-terminal functional domain that uncouples ATP hydrolysis from strand separation activity. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

A Cross-Domain Collaborative Filtering Algorithm Based on Feature Construction and Locally Weighted Linear Regression

PubMed Central

Jiang, Feng; Han, Ji-zhong

2018-01-01

Cross-domain collaborative filtering (CDCF) solves the sparsity problem by transferring rating knowledge from auxiliary domains. Obviously, different auxiliary domains have different importance to the target domain. However, previous works cannot evaluate effectively the significance of different auxiliary domains. To overcome this drawback, we propose a cross-domain collaborative filtering algorithm based on Feature Construction and Locally Weighted Linear Regression (FCLWLR). We first construct features in different domains and use these features to represent different auxiliary domains. Thus the weight computation across different domains can be converted as the weight computation across different features. Then we combine the features in the target domain and in the auxiliary domains together and convert the cross-domain recommendation problem into a regression problem. Finally, we employ a Locally Weighted Linear Regression (LWLR) model to solve the regression problem. As LWLR is a nonparametric regression method, it can effectively avoid underfitting or overfitting problem occurring in parametric regression methods. We conduct extensive experiments to show that the proposed FCLWLR algorithm is effective in addressing the data sparsity problem by transferring the useful knowledge from the auxiliary domains, as compared to many state-of-the-art single-domain or cross-domain CF methods. PMID:29623088

A Cross-Domain Collaborative Filtering Algorithm Based on Feature Construction and Locally Weighted Linear Regression.

PubMed

Yu, Xu; Lin, Jun-Yu; Jiang, Feng; Du, Jun-Wei; Han, Ji-Zhong

2018-01-01

Cross-domain collaborative filtering (CDCF) solves the sparsity problem by transferring rating knowledge from auxiliary domains. Obviously, different auxiliary domains have different importance to the target domain. However, previous works cannot evaluate effectively the significance of different auxiliary domains. To overcome this drawback, we propose a cross-domain collaborative filtering algorithm based on Feature Construction and Locally Weighted Linear Regression (FCLWLR). We first construct features in different domains and use these features to represent different auxiliary domains. Thus the weight computation across different domains can be converted as the weight computation across different features. Then we combine the features in the target domain and in the auxiliary domains together and convert the cross-domain recommendation problem into a regression problem. Finally, we employ a Locally Weighted Linear Regression (LWLR) model to solve the regression problem. As LWLR is a nonparametric regression method, it can effectively avoid underfitting or overfitting problem occurring in parametric regression methods. We conduct extensive experiments to show that the proposed FCLWLR algorithm is effective in addressing the data sparsity problem by transferring the useful knowledge from the auxiliary domains, as compared to many state-of-the-art single-domain or cross-domain CF methods.

De novo design and engineering of functional metal and porphyrin-binding protein domains

NASA Astrophysics Data System (ADS)

Everson, Bernard H.

In this work, I describe an approach to the rational, iterative design and characterization of two functional cofactor-binding protein domains. First, a hybrid computational/experimental method was developed with the aim of algorithmically generating a suite of porphyrin-binding protein sequences with minimal mutual sequence information. This method was explored by generating libraries of sequences, which were then expressed and evaluated for function. One successful sequence is shown to bind a variety of porphyrin-like cofactors, and exhibits light- activated electron transfer in mixed hemin:chlorin e6 and hemin:Zn(II)-protoporphyrin IX complexes. These results imply that many sophisticated functions such as cofactor binding and electron transfer require only a very small number of residue positions in a protein sequence to be fixed. Net charge and hydrophobic content are important in determining protein solubility and stability. Accordingly, rational modifications were made to the aforementioned design procedure in order to improve its overall success rate. The effects of these modifications are explored using two `next-generation' sequence libraries, which were separately expressed and evaluated. Particular modifications to these design parameters are demonstrated to effectively double the purification success rate of the procedure. Finally, I describe the redesign of the artificial di-iron protein DF2 into CDM13, a single chain di-Manganese four-helix bundle. CDM13 acts as a functional model of natural manganese catalase, exhibiting a kcat of 0.08s-1 under steady-state conditions. The bound manganese cofactors have a reduction potential of +805 mV vs NHE, which is too high for efficient dismutation of hydrogen peroxide. These results indicate that as a high-potential manganese complex, CDM13 may represent a promising first step toward a polypeptide model of the Oxygen Evolving Complex of the photosynthetic enzyme Photosystem II.

Membrane Localization is Critical for Activation of the PICK1 BAR Domain

PubMed Central

Madsen, Kenneth L.; Eriksen, Jacob; Milan-Lobo, Laura; Han, Daniel S.; Niv, Masha Y.; Ammendrup-Johnsen, Ina; Henriksen, Ulla; Bhatia, Vikram K.; Stamou, Dimitrios; Sitte, Harald H.; McMahon, Harvey T.; Weinstein, Harel; Gether, Ulrik

2013-01-01

The PSD-95/Discs-large/ZO-1 homology (PDZ) domain protein, protein interacting with C kinase 1 (PICK1) contains a C-terminal Bin/amphiphysin/Rvs (BAR) domain mediating recognition of curved membranes; however, the molecular mechanisms controlling the activity of this domain are poorly understood. In agreement with negative regulation of the BAR domain by the N-terminal PDZ domain, PICK1 distributed evenly in the cytoplasm, whereas truncation of the PDZ domain caused BAR domain-dependent redistribution to clusters colocalizing with markers of recycling endosomal compartments. A similar clustering was observed both upon truncation of a short putative α-helical segment in the linker between the PDZ and the BAR domains and upon coexpression of PICK1 with a transmembrane PDZ ligand, including the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR2 subunit, the GluR2 C-terminus transferred to the single transmembrane protein Tac or the dopamine transporter C-terminus transferred to Tac. In contrast, transfer of the GluR2 C-terminus to cyan fluorescent protein, a cytosolic protein, did not elicit BAR domain-dependent clustering. Instead, localizing PICK1 to the membrane by introducing an N-terminal myristoylation site produced BAR domain-dependent, but ligand-independent, PICK1 clustering. The data support that in the absence of PDZ ligand, the PICK1 BAR domain is inhibited through a PDZ domain-dependent and linker-dependent mechanism. Moreover, they suggest that unmasking of the BAR domain’s membrane-binding capacity is not a consequence of ligand binding to the PDZ domain per se but results from, and coincides with, recruitment of PICK1 to a membrane compartment. PMID:18466293

Does expert perceptual anticipation transfer to a dissimilar domain?

PubMed

Müller, Sean; McLaren, Michelle; Appleby, Brendyn; Rosalie, Simon M

2015-06-01

The purpose of this experiment was to extend theoretical understanding of transfer of learning by investigating whether expert perceptual anticipation skill transfers to a dissimilar domain. The capability of expert and near-expert rugby players as well as novices to anticipate skill type within rugby (learning sport) was first examined using a temporal occlusion paradigm. Participants watched video footage of an opponent performing rugby skill types that were temporally occluded at different points in the opponent's action and then made a written prediction. Thereafter, the capability of participants to transfer their anticipation skill to predict pitch type in baseball (transfer sport) was examined. Participants watched video footage of a pitcher throwing different pitch types that were temporally occluded and made a written prediction. Results indicated that expert and near-expert rugby players anticipated significantly better than novices across all occlusion conditions. However, none of the skill groups were able to transfer anticipation skill to predict pitch type in baseball. The findings of this paper, along with existing literature, support the theoretical prediction that transfer of perceptual anticipation is expertise dependent and restricted to similar domains. (c) 2015 APA, all rights reserved).

Molecular dynamics simulations elucidate the mode of protein recognition by Skp1 and the F-box domain in the SCF complex.

PubMed

Chandra Dantu, Sarath; Nathubhai Kachariya, Nitin; Kumar, Ashutosh

2016-01-01

Polyubiquitination of the target protein by a ubiquitin transferring machinery is key to various cellular processes. E3 ligase Skp1-Cul1-F-box (SCF) is one such complex which plays crucial role in substrate recognition and transfer of the ubiquitin molecule. Previous computational studies have focused on S-phase kinase-associated protein 2 (Skp2), cullin, and RING-finger proteins of this complex, but the roles of the adapter protein Skp1 and F-box domain of Skp2 have not been determined. Using sub-microsecond molecular dynamics simulations of full-length Skp1, unbound Skp2, Skp2-Cks1 (Cks1: Cyclin-dependent kinases regulatory subunit 1), Skp1-Skp2, and Skp1-Skp2-Cks1 complexes, we have elucidated the function of Skp1 and the F-box domain of Skp2. We found that the L16 loop of Skp1, which was deleted in previous X-ray crystallography studies, can offer additional stability to the ternary complex via its interactions with the C-terminal tail of Skp2. Moreover, Skp1 helices H6, H7, and H8 display vivid conformational flexibility when not bound to Skp2, suggesting that these helices can recognize and lock the F-box proteins. Furthermore, we observed that the F-box domain could rotate (5°-129°), and that the binding partner determined the degree of conformational flexibility. Finally, Skp1 and Skp2 were found to execute a domain motion in Skp1-Skp2 and Skp1-Skp2-Cks1 complexes that could decrease the distance between ubiquitination site of the substrate and the ubiquitin molecule by 3 nm. Thus, we propose that both the F-box domain of Skp2 and Skp1-Skp2 domain motions displaying preferential conformational control can together facilitate polyubiquitination of a wide variety of substrates. © 2015 Wiley Periodicals, Inc.

INCENP Centromere and Spindle Targeting: Identification of Essential Conserved Motifs and Involvement of Heterochromatin Protein HP1

PubMed Central

Ainsztein, Alexandra M.; Kandels-Lewis, Stefanie E.; Mackay, Alastair M.; Earnshaw, William C.

1998-01-01

The inner centromere protein (INCENP) has a modular organization, with domains required for chromosomal and cytoskeletal functions concentrated near the amino and carboxyl termini, respectively. In this study we have identified an autonomous centromere- and midbody-targeting module in the amino-terminal 68 amino acids of INCENP. Within this module, we have identified two evolutionarily conserved amino acid sequence motifs: a 13–amino acid motif that is required for targeting to centromeres and transfer to the spindle, and an 11–amino acid motif that is required for transfer to the spindle by molecules that have targeted previously to the centromere. To begin to understand the mechanisms of INCENP function in mitosis, we have performed a yeast two-hybrid screen for interacting proteins. These and subsequent in vitro binding experiments identify a physical interaction between INCENP and heterochromatin protein HP1Hsα. Surprisingly, this interaction does not appear to be involved in targeting INCENP to the centromeric heterochromatin, but may instead have a role in its transfer from the chromosomes to the anaphase spindle. PMID:9864353

Theoretical linear approach to the combined man-manipulator system in manual control of an aircraft

NASA Technical Reports Server (NTRS)

Brauser, K.

1981-01-01

An approach to the calculation of the dynamic characteristics of the combined man manipulator system in manual aircraft control was derived from a model of the neuromuscular system. This model combines the neuromuscular properties of man with the physical properties of the manipulator system which is introduced as pilot manipulator model into the manual aircraft control. The assumption of man as a quasilinear and time invariant control operator adapted to operating states, depending on the flight phases, of the control system gives rise to interesting solutions of the frequency domain transfer functions of both the man manipulator system and the closed loop pilot aircraft control system. It is shown that it is necessary to introduce the complete precision pilot manipulator model into the closed loop pilot aircraft transfer function in order to understand the well known handling quality criteria, and to derive these criteria directly from human operator properties.

SIG: a general-purpose signal processing program

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

Lager, D.; Azevedo, S.

1986-02-01

SIG is a general-purpose signal processing, analysis, and display program. Its main purpose is to perform manipulations on time- and frequency-domain signals. It also accommodates other representations for data such as transfer function polynomials. Signal processing operations include digital filtering, auto/cross spectral density, transfer function/impulse response, convolution, Fourier transform, and inverse Fourier transform. Graphical operations provide display of signals and spectra, including plotting, cursor zoom, families of curves, and multiple viewport plots. SIG provides two user interfaces with a menu mode for occasional users and a command mode for more experienced users. Capability exits for multiple commands per line, commandmore » files with arguments, commenting lines, defining commands, automatic execution for each item in a repeat sequence, etc. SIG is presently available for VAX(VMS), VAX (BERKELEY 4.2 UNIX), SUN (BERKELEY 4.2 UNIX), DEC-20 (TOPS-20), LSI-11/23 (TSX), and DEC PRO 350 (TSX). 4 refs., 2 figs.« less

Sam37 is crucial for formation of the mitochondrial TOM-SAM supercomplex, thereby promoting β-barrel biogenesis.

PubMed

Wenz, Lena-Sophie; Ellenrieder, Lars; Qiu, Jian; Bohnert, Maria; Zufall, Nicole; van der Laan, Martin; Pfanner, Nikolaus; Wiedemann, Nils; Becker, Thomas

2015-09-28

Biogenesis of mitochondrial β-barrel proteins requires two preprotein translocases, the general translocase of the outer membrane (TOM) and the sorting and assembly machinery (SAM). TOM and SAM form a supercomplex that promotes transfer of β-barrel precursors. The SAM core complex contains the channel protein Sam50, which cooperates with Sam35 in precursor recognition, and the peripheral membrane protein Sam37. The molecular function of Sam37 has been unknown. We report that Sam37 is crucial for formation of the TOM-SAM supercomplex. Sam37 interacts with the receptor domain of Tom22 on the cytosolic side of the mitochondrial outer membrane and links TOM and SAM complexes. Sam37 thus promotes efficient transfer of β-barrel precursors to the SAM complex. We conclude that Sam37 functions as a coupling factor of the translocase supercomplex of the mitochondrial outer membrane. © 2015 Wenz et al.

Trajectory optimization of spacecraft high-thrust orbit transfer using a modified evolutionary algorithm

NASA Astrophysics Data System (ADS)

Shirazi, Abolfazl

2016-10-01

This article introduces a new method to optimize finite-burn orbital manoeuvres based on a modified evolutionary algorithm. Optimization is carried out based on conversion of the orbital manoeuvre into a parameter optimization problem by assigning inverse tangential functions to the changes in direction angles of the thrust vector. The problem is analysed using boundary delimitation in a common optimization algorithm. A method is introduced to achieve acceptable values for optimization variables using nonlinear simulation, which results in an enlarged convergence domain. The presented algorithm benefits from high optimality and fast convergence time. A numerical example of a three-dimensional optimal orbital transfer is presented and the accuracy of the proposed algorithm is shown.

Cross-domain question classification in community question answering via kernel mapping

NASA Astrophysics Data System (ADS)

Su, Lei; Hu, Zuoliang; Yang, Bin; Li, Yiyang; Chen, Jun

2015-10-01

An increasingly popular method for retrieving information is via the community question answering (CQA) systems such as Yahoo! Answers and Baidu Knows. In CQA, question classification plays an important role to find the answers. However, the labeled training examples for statistical question classifier are fairly expensive to obtain, as they require the experienced human efforts. Meanwhile, unlabeled data are readily available. This paper employs the method of domain adaptation via kernel mapping to solve this problem. In detail, the kernel approach is utilized to map the target-domain data and the source-domain data into a common space, where the question classifiers are trained under the closer conditional probabilities. The kernel mapping function is constructed by domain knowledge. Therefore, domain knowledge could be transferred from the labeled examples in the source domain to the unlabeled ones in the targeted domain. The statistical training model can be improved by using a large number of unlabeled data. Meanwhile, the Hadoop Platform is used to construct the mapping mechanism to reduce the time complexity. Map/Reduce enable kernel mapping for domain adaptation in parallel in the Hadoop Platform. Experimental results show that the accuracy of question classification could be improved by the method of kernel mapping. Furthermore, the parallel method in the Hadoop Platform could effective schedule the computing resources to reduce the running time.

Multivariable frequency domain identification via 2-norm minimization

NASA Technical Reports Server (NTRS)

Bayard, David S.

1992-01-01

The author develops a computational approach to multivariable frequency domain identification, based on 2-norm minimization. In particular, a Gauss-Newton (GN) iteration is developed to minimize the 2-norm of the error between frequency domain data and a matrix fraction transfer function estimate. To improve the global performance of the optimization algorithm, the GN iteration is initialized using the solution to a particular sequentially reweighted least squares problem, denoted as the SK iteration. The least squares problems which arise from both the SK and GN iterations are shown to involve sparse matrices with identical block structure. A sparse matrix QR factorization method is developed to exploit the special block structure, and to efficiently compute the least squares solution. A numerical example involving the identification of a multiple-input multiple-output (MIMO) plant having 286 unknown parameters is given to illustrate the effectiveness of the algorithm.

Vertically-Integrated Dual-Continuum Models for CO2 Injection in Fractured Aquifers

NASA Astrophysics Data System (ADS)

Tao, Y.; Guo, B.; Bandilla, K.; Celia, M. A.

2017-12-01

Injection of CO2 into a saline aquifer leads to a two-phase flow system, with supercritical CO2 and brine being the two fluid phases. Various modeling approaches, including fully three-dimensional (3D) models and vertical-equilibrium (VE) models, have been used to study the system. Almost all of that work has focused on unfractured formations. 3D models solve the governing equations in three dimensions and are applicable to generic geological formations. VE models assume rapid and complete buoyant segregation of the two fluid phases, resulting in vertical pressure equilibrium and allowing integration of the governing equations in the vertical dimension. This reduction in dimensionality makes VE models computationally more efficient, but the associated assumptions restrict the applicability of VE model to formations with moderate to high permeability. In this presentation, we extend the VE and 3D models for CO2 injection in fractured aquifers. This is done in the context of dual-continuum modeling, where the fractured formation is modeled as an overlap of two continuous domains, one representing the fractures and the other representing the rock matrix. Both domains are treated as porous media continua and can be modeled by either a VE or a 3D formulation. The transfer of fluid mass between rock matrix and fractures is represented by a mass transfer function connecting the two domains. We have developed a computational model that combines the VE and 3D models, where we use the VE model in the fractures, which typically have high permeability, and the 3D model in the less permeable rock matrix. A new mass transfer function is derived, which couples the VE and 3D models. The coupled VE-3D model can simulate CO2 injection and migration in fractured aquifers. Results from this model compare well with a full-3D model in which both the fractures and rock matrix are modeled with 3D models, with the hybrid VE-3D model having significantly reduced computational cost. In addition to the VE-3D model, we explore simplifications of the rock matrix domain by using sugar-cube and matchstick conceptualizations and develop VE-dual porosity and VE-matchstick models. These vertically-integrated dual-permeability and dual-porosity models provide a range of computationally efficient tools to model CO2 storage in fractured saline aquifers.

E-microsatellite markers for Centella asiatica (Gotu Kola) genome: validation and cross-transferability in Apiaceae family for plant omics research and development.

PubMed

Sahu, Jagajjit; Das Talukdar, Anupam; Devi, Kamalakshi; Choudhury, Manabendra Dutta; Barooah, Madhumita; Modi, Mahendra Kumar; Sen, Priyabrata

2015-01-01

Abstract Centella asiatica (Gotu Kola) is a plant that grows in tropical swampy regions of the world and has important medicinal and culinary use. It is often considered as part of Ayurvedic medicine, traditional African medicine, and traditional Chinese medicine. The unavailability of genomics resources is significantly impeding its genetic improvement. To date, no attempt has been made to develop Expressed Sequence Tags (ESTs) derived Simple Sequence Repeat (SSR) markers (eSSRs) from the Centella genome. Hence, the present study aimed to develop eSSRs and their further experimental validation and cross-transferability of these markers in different genera of the Apiaceae family to which Centella belongs. An in-house pipeline was developed for the entire analyses by combining bioinformatics tools and perl scripts. A total of 4443 C. asiatica EST sequences from dbEST were processed, which generated 2617 nonredundant high quality EST sequences consisting 441 contigs and 2176 singletons. Out of 1776.5 kb of examined sequences, 417 (15.9%) ESTs containing 686 SSRs were detected with a density of one SSR per 2.59 kb. The gene ontology study revealed 282 functional domains involved in various processes, components, and functions, out of which 64 ESTs were found to have both SSRs and functional domains. Out of 603 designed EST-SSR primers, 18 pairs of primers were selected for validation based on the optimum parameter value. Reproducible amplification was obtained for six primer pairs in C. asiatica that were further tested for cross-transferability in nine other important genera/species of the Apiaceae family. Cross-transferability of the EST-SSR markers among the species were examined and Centella javanica showed highest transferability (83.3%). The study revealed six highly polymorphic EST-SSR primers with an average PIC value of 0.95. In conclusion, these EST-SSR markers hold a big promise for the genomics analysis of Centella asiatica, to facilitate comparative map-based analyses across other related species within the Apiaceae family, and future marker-assisted breeding programs. To the best of our knowledge, this is the first report of development of EST-SSRs in Centella asiatica by in silico approaches, which offers a veritable potential in further use in plant omics research and development.

Cross-domain transfer of quantitative discriminations: is it all a matter of proportion?

PubMed

Balci, Fuat; Gallistel, Charles R

2006-08-01

Meck and Church (1983) estimated a 5:1 scale factor relating the mental magnitudes representing number to the mental magnitudes representing duration. We repeated their experiment with human subjects. We obtained transfer regardless of the objective scaling between the ranges; a 5:1 scaling for number versus duration (measured in seconds) was not necessary. We obtained transfer even when the proportions between the endpoints of the number range were different. We conclude that, at least in human subjects, transfer from a discrimination based on continuous quantity (duration) to a discrimination based on discrete quantity (number) is mediated by the cross-domain comparability of within-domain proportions. The results of our second and third experiments also suggest that the subjects compare a probe with a criterion determined by the range of stimuli tested rather than by trial-specific referents, in accordance with the pseudologistic model of Killeen, Fetterman, and Bizo (1997).

Intuitive Exploration of Volumetric Data Using Dynamic Galleries.

PubMed

Jönsson, Daniel; Falk, Martin; Ynnerman, Anders

2016-01-01

In this work we present a volume exploration method designed to be used by novice users and visitors to science centers and museums. The volumetric digitalization of artifacts in museums is of rapidly increasing interest as enhanced user experience through interactive data visualization can be achieved. This is, however, a challenging task since the vast majority of visitors are not familiar with the concepts commonly used in data exploration, such as mapping of visual properties from values in the data domain using transfer functions. Interacting in the data domain is an effective way to filter away undesired information but it is difficult to predict where the values lie in the spatial domain. In this work we make extensive use of dynamic previews instantly generated as the user explores the data domain. The previews allow the user to predict what effect changes in the data domain will have on the rendered image without being aware that visual parameters are set in the data domain. Each preview represents a subrange of the data domain where overview and details are given on demand through zooming and panning. The method has been designed with touch interfaces as the target platform for interaction. We provide a qualitative evaluation performed with visitors to a science center to show the utility of the approach.

Lipid-Coated Gold Nanoparticles and FRET Allow Sensitive Monitoring of Liposome Clustering Mediated by the Synaptotagmin-7 C2A Domain.

PubMed

Hamilton, Desmond J; Coffman, Matthew D; Knight, Jefferson D; Reed, Scott M

2017-09-12

Synaptotagmin (Syt) family proteins contain tandem C2 domains, C2A and C2B, which insert into anionic membranes in response to increased cytosolic Ca 2+ concentration and facilitate exocytosis in neuronal and endocrine cells. The C2A domain from Syt7 binds lipid membranes much more tightly than the corresponding domain from Syt1, but the implications of this difference for protein function are not yet clear. In particular, the ability of the isolated Syt7 C2A domain to initiate membrane apposition and/or aggregation has been previously unexplored. Here, we demonstrate that Syt7 C2A induces apposition and aggregation of liposomes using Förster resonance energy transfer (FRET) assays, dynamic light scattering, and spectroscopic techniques involving lipid-coated gold nanoparticles (LCAuNPs). Protein-membrane binding, membrane apposition, and macroscopic aggregation are three separate phenomena with distinct Ca 2+ requirements: the threshold Ca 2+ concentration for membrane binding is lowest, followed by apposition and aggregation. However, aggregation is highly sensitive to protein concentration and can occur even at submicromolar Syt7 C2A; thus, highly sensitive assays are needed for measuring apposition without complications arising from aggregation. Notably, the localized surface plasmon resonance of the LCAuNP is sensitive to ≤10 nM Syt7 C2A concentrations. Furthermore, when the LCAuNPs were added into a FRET-based liposome apposition assay, the resultant energy transfer increased; possible explanations are discussed. Overall, LCAuNP-based methods allow for highly sensitive detection of protein-induced membrane apposition under conditions that miminize large-scale aggregation.

Complete spatiotemporal characterization and optical transfer matrix inversion of a 420 mode fiber.

PubMed

Carpenter, Joel; Eggleton, Benjamin J; Schröder, Jochen

2016-12-01

The ability to measure a scattering medium's optical transfer matrix, the mapping between any spatial input and output, has enabled applications such as imaging to be performed through media which would otherwise be opaque due to scattering. However, the scattering of light occurs not just in space, but also in time. We complete the characterization of scatter by extending optical transfer matrix methods into the time domain, allowing any spatiotemporal input state at one end to be mapped directly to its corresponding spatiotemporal output state. We have measured the optical transfer function of a multimode fiber in its entirety; it consists of 420 modes in/out at 32768 wavelengths, the most detailed complete characterization of multimode waveguide light propagation to date, to the best of our knowledge. We then demonstrate the ability to generate any spatial/polarization state at the output of the fiber at any wavelength, as well as predict the temporal response of any spatial/polarization input state.

Kinetics of interprotein electron transfer between cytochrome c6 and the soluble CuA domain of cyanobacterial cytochrome c oxidase.

PubMed

Paumann, Martina; Feichtinger, Markus; Bernroitner, Margit; Goldfuhs, Judith; Jakopitsch, Christa; Furtmüller, Paul G; Regelsberger, Günther; Peschek, Günter A; Obinger, Christian

2004-10-08

Cytochrome c6 is a soluble metalloprotein located in the periplasmic space and the thylakoid lumen of many cyanobacteria and is known to carry electrons from cytochrome b6f to photosystem I. The CuA domain of cytochrome c oxidase, the terminal enzyme which catalyzes the four-electron reduction of molecular oxygen in the respiratory chains of mitochondria and many bacteria, also has a periplasmic location. In order to test whether cytochrome c6 could also function as a donor for cytochrome c oxidase, we investigated the kinetics of the electron transfer between recombinant cytochrome c6 (produced in high yield in Escherichia coli by coexpressing the maturation proteins encoded by the ccmA-H gene cluster) and the recombinant soluble CuA domain (i.e., the donor binding and electron entry site) of subunit II of cytochrome c oxidase from Synechocystis PCC 6803. The forward and the reverse electron transfer reactions were studied by the stopped-flow technique and yielded apparent bimolecular rate constants of (3.3 +/- 0.3) x 10(5) M(-1) s(-1) and (3.9 +/- 0.1) x 10(6) M(-1) s(-1), respectively, in 5 mM potassium phosphate buffer, pH 7, containing 20 mM potassium chloride and 25 degrees C. This corresponds to an equilibrium constant Keq of 0.085 in the physiological direction (DeltarG'0 = 6.1 kJ/mol). The reduction of the CuA fragment by cytochrome c6 is almost independent on ionic strength, which is in contrast to the reaction of the CuA domain with horse heart cytochrome c, which decreases with increasing ionic strength. The findings are discussed with respect to the potential role of cytochrome c6 as mobile electron carrier in both cyanobacterial electron transport pathways. Copyright 2004 Federation of European Biochemical Societies

Unravelling Responses for the Canadian National Seismic Network

NASA Astrophysics Data System (ADS)

Mulder, T. L.

2009-12-01

There are a number of attendant difficulties any network must deal with that range from defining the transfer function to instrument naming conventions to choices of final local file format representation. These choices ultimately result in the ease of conversion to other data formats and therefore directly impact useability. In particular, the ease of data exhange and use of established software that is dependent on standard data types is impacted. This becomes particularly critical with large (terabyte) dataset processing and when integrating external datasets into analysis procedures. Transfer functions, often referred to as instrument responses, are a key component in describing instrumentation. The transfer function describes the complete response of the seismic system. The seismic system is designed to be a linear system that can be decomposed into discrete components. Analogue or digital convolution can be represented as multiplication in the frequency domain. The two basic elements of a seismic system are the sensor and datalogger. The analogue sensor can be represented mathmatically as poles and zeroes. The datalogger can be further broken down into its discrete analogue and digital components: the preamp, A/D converter, and fir filters. The Canadian seismic network (CNSN) digitizers have an additional complication. To save telemetry band-width, the 32 bit signal from the digitizer has a transmission gain removed. The transmission gain (txgain) represents the number of the least significant bits truncated from the sample (2^txgain) after which the data is compressed and transmitted. While telemetry band-width is not the issue it was, now that many sites have ip connectivity, this user programmable transmission gain is still in use and can vary from station to station. The processes receiving the transmitted data do not restore the pre-transmission scaling, consequently the archived waveform files can vary in bit weight over time from station to station depending on the value of the transmission gain. Consequently the transmission gain must be factored into the transfer function. This presentation describes the process for generating the transfer function based on the constituent components discussed here. A matlab routine run on the database generates the transfer function plots for the network.

Excitation of Terahertz Charge Transfer Plasmons in Metallic Fractal Structures

NASA Astrophysics Data System (ADS)

Ahmadivand, Arash; Gerislioglu, Burak; Sinha, Raju; Vabbina, Phani Kiran; Karabiyik, Mustafa; Pala, Nezih

2017-08-01

There have been extensive researches on terahertz (THz) plasmonic structures supporting resonant modes to demonstrate nano and microscale devices with high efficiency and responsivity as well as frequency selectivity. Here, using antisymmetric plasmonic fractal Y-shaped (FYS) structures as building blocks, we introduce a highly tunable four-member fractal assembly to support charge transfer plasmons (CTPs) and classical dipolar resonant modes with significant absorption cross section in the THz domain. We first present that the unique geometrical nature of the FYS system and corresponding spectral response allow for supporting intensified dipolar plasmonic modes under polarised light exposure in a standalone structure. In addition to classical dipolar mode, for the very first time, we demonstrated CTPs in the THz domain due to the direct shuttling of the charges across the metallic fractal microantenna which led to sharp resonant absorption peaks. Using both numerical and experimental studies, we have investigated and confirmed the excitation of the CTP modes and highly tunable spectral response of the proposed plasmonic fractal structure. This understanding opens new and promising horizons for tightly integrated THz devices with high efficiency and functionality.

Tackling force-field bias in protein folding simulations: folding of Villin HP35 and Pin WW domains in explicit water.

PubMed

Mittal, Jeetain; Best, Robert B

2010-08-04

The ability to fold proteins on a computer has highlighted the fact that existing force fields tend to be biased toward a particular type of secondary structure. Consequently, force fields for folding simulations are often chosen according to the native structure, implying that they are not truly "transferable." Here we show that, while the AMBER ff03 potential is known to favor helical structures, a simple correction to the backbone potential (ff03( *)) results in an unbiased energy function. We take as examples the 35-residue alpha-helical Villin HP35 and 37 residue beta-sheet Pin WW domains, which had not previously been folded with the same force field. Starting from unfolded configurations, simulations of both proteins in Amber ff03( *) in explicit solvent fold to within 2.0 A RMSD of the experimental structures. This demonstrates that a simple backbone correction results in a more transferable force field, an important requirement if simulations are to be used to interpret folding mechanism. 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Time-domain ab initio modeling of photoinduced dynamics at nanoscale interfaces.

PubMed

Wang, Linjun; Long, Run; Prezhdo, Oleg V

2015-04-01

Nonequilibrium processes involving electronic and vibrational degrees of freedom in nanoscale materials are under active experimental investigation. Corresponding theoretical studies are much scarcer. The review starts with the basics of time-dependent density functional theory, recent developments in nonadiabatic molecular dynamics, and the fusion of the two techniques. Ab initio simulations of this kind allow us to directly mimic a great variety of time-resolved experiments performed with pump-probe laser spectroscopies. The focus is on the ultrafast photoinduced charge and exciton dynamics at interfaces formed by two complementary materials. We consider purely inorganic materials, inorganic-organic hybrids, and all organic interfaces, involving bulk semiconductors, metallic and semiconducting nanoclusters, graphene, carbon nanotubes, fullerenes, polymers, molecular crystals, molecules, and solvent. The detailed atomistic insights available from time-domain ab initio studies provide a unique description and a comprehensive understanding of the competition between electron transfer, thermal relaxation, energy transfer, and charge recombination processes. These advances now make it possible to directly guide the development of organic and hybrid solar cells, as well as photocatalytic, electronic, spintronic, and other devices relying on complex interfacial dynamics.

Extending brain-training to the affective domain: increasing cognitive and affective executive control through emotional working memory training.

PubMed

Schweizer, Susanne; Hampshire, Adam; Dalgleish, Tim

2011-01-01

So-called 'brain-training' programs are a huge commercial success. However, empirical evidence regarding their effectiveness and generalizability remains equivocal. This study investigated whether brain-training (working memory [WM] training) improves cognitive functions beyond the training task (transfer effects), especially regarding the control of emotional material since it constitutes much of the information we process daily. Forty-five participants received WM training using either emotional or neutral material, or an undemanding control task. WM training, regardless of training material, led to transfer gains on another WM task and in fluid intelligence. However, only brain-training with emotional material yielded transferable gains to improved control over affective information on an emotional Stroop task. The data support the reality of transferable benefits of demanding WM training and suggest that transferable gains across to affective contexts require training with material congruent to those contexts. These findings constitute preliminary evidence that intensive cognitively demanding brain-training can improve not only our abstract problem-solving capacity, but also ameliorate cognitive control processes (e.g. decision-making) in our daily emotive environments.

Spectral collocation method with a flexible angular discretization scheme for radiative transfer in multi-layer graded index medium

NASA Astrophysics Data System (ADS)

Wei, Linyang; Qi, Hong; Sun, Jianping; Ren, Yatao; Ruan, Liming

2017-05-01

The spectral collocation method (SCM) is employed to solve the radiative transfer in multi-layer semitransparent medium with graded index. A new flexible angular discretization scheme is employed to discretize the solid angle domain freely to overcome the limit of the number of discrete radiative direction when adopting traditional SN discrete ordinate scheme. Three radial basis function interpolation approaches, named as multi-quadric (MQ), inverse multi-quadric (IMQ) and inverse quadratic (IQ) interpolation, are employed to couple the radiative intensity at the interface between two adjacent layers and numerical experiments show that MQ interpolation has the highest accuracy and best stability. Variable radiative transfer problems in double-layer semitransparent media with different thermophysical properties are investigated and the influence of these thermophysical properties on the radiative transfer procedure in double-layer semitransparent media is also analyzed. All the simulated results show that the present SCM with the new angular discretization scheme can predict the radiative transfer in multi-layer semitransparent medium with graded index efficiently and accurately.

Domain-Specific Partitioning of Uterine Artery Endothelial Connexin43 and Caveolin-1.

PubMed

Ampey, Bryan C; Morschauser, Timothy J; Ramadoss, Jayanth; Magness, Ronald R

2016-10-01

Uterine vascular adaptations facilitate rises in uterine blood flow during pregnancy, which are associated with gap junction connexin (Cx) proteins and endothelial nitric oxide synthase. In uterine artery endothelial cells (UAECs), ATP activates endothelial nitric oxide synthase in a pregnancy (P)-specific manner that is dependent on Cx43 function. Caveolar subcellular domain partitioning plays key roles in ATP-induced endothelial nitric oxide synthase activation and nitric oxide production. Little is known regarding the partitioning of Cx proteins to caveolar domains or their dynamics with ATP treatment. We observed that Cx43-mediated gap junction function with ATP stimulation is associated with Cx43 repartitioning between the noncaveolar and caveolar domains. Compared with UAECs from nonpregnant (NP) ewes, levels of ATP, PGI2, cAMP, NOx, and cGMP were 2-fold higher (P<0.05) in pregnant UAECs. In pregnant UAECs, ATP increased Lucifer yellow dye transfer, a response abrogated by Gap27, but not Gap 26, indicating involvement of Cx43, but not Cx37. Confocal microscopy revealed domain partitioning of Cx43 and caveolin-1. In pregnant UAECs, LC/MS/MS analysis revealed only Cx43 in the caveolar domain. In contrast, Cx37 was located only in the noncaveolar pool. Western analysis revealed that ATP increased Cx43 distribution (1.7-fold; P=0.013) to the caveolar domain, but had no effect on Cx37. These data demonstrate rapid ATP-stimulated repartitioning of Cx43 to the caveolae, where endothelial nitric oxide synthase resides and plays an important role in nitric oxide-mediated increasing uterine blood flow during pregnancy. © 2016 American Heart Association, Inc.

The yeasts phosphorelay systems: a comparative view.

PubMed

Salas-Delgado, Griselda; Ongay-Larios, Laura; Kawasaki-Watanabe, Laura; López-Villaseñor, Imelda; Coria, Roberto

2017-06-01

Cells contain signal transduction pathways that mediate communication between the extracellular environment and the cell interior. These pathways control transcriptional programs and posttranscriptional processes that modify cell metabolism in order to maintain homeostasis. One type of these signal transduction systems are the so-called Two Component Systems (TCS), which conduct the transfer of phosphate groups between specific and conserved histidine and aspartate residues present in at least two proteins; the first protein is a sensor kinase which autophosphorylates a histidine residue in response to a stimulus, this phosphate is then transferred to an aspartic residue located in a response regulator protein. There are classical and hybrid TCS, whose difference consists in the number of proteins and functional domains involved in the phosphorelay. The TCS are widespread in bacteria where the sensor and its response regulator are mostly specific for a given stimulus. In eukaryotic organisms such as fungi, slime molds, and plants, TCS are present as hybrid multistep phosphorelays, with a variety of arrangements (Stock et al. in Annu Rev Biochem 69:183-215, 2000; Wuichet et al. in Curr Opin Microbiol 292:1039-1050, 2010). In these multistep phosphorelay systems, several phosphotransfer events take place between different histidine and aspartate residues localized in specific domains present in more than two proteins (Thomason and Kay, in J Cell Sci 113:3141-3150, 2000; Robinson et al. in Nat Struct Biol 7:626-633, 2000). This review presents a brief and succinct description of the Two-component systems of model yeasts, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans, Cryptococcus neoformans and Kluyveromyces lactis. We have focused on the comparison of domain organization and functions of each component present in these phosphorelay systems.

Electrical characterization of non‐Fickian transport in groundwater and hyporheic systems

USGS Publications Warehouse

Singha, Kamini; Pidlisecky, Adam; Day-Lewis, Frederick D.; Gooseff, Michael N.

2008-01-01

Recent work indicates that processes controlling solute mass transfer between mobile and less mobile domains in porous media may be quantified by combining electrical geophysical methods and electrically conductive tracers. Whereas direct geochemical measurements of solute preferentially sample the mobile domain, electrical geophysical methods are sensitive to changes in bulk electrical conductivity (bulk EC) and therefore sample EC in both the mobile and immobile domains. Consequently, the conductivity difference between direct geochemical samples and remotely sensed electrical geophysical measurements may provide an indication of mass transfer rates and mobile and immobile porosities in situ. Here we present (1) an overview of a theoretical framework for determining parameters controlling mass transfer with electrical resistivity in situ; (2) a review of a case study estimating mass transfer processes in a pilot‐scale aquifer storage recovery test; and (3) an example application of this method for estimating mass transfer in watershed settings between streams and the hyporheic corridor. We demonstrate that numerical simulations of electrical resistivity studies of the stream/hyporheic boundary can help constrain volumes and rates of mobile‐immobile mass transfer. We conclude with directions for future research applying electrical geophysics to understand field‐scale transport in aquifer and fluvial systems subject to rate‐limited mass transfer.

Do pattern recognition skills transfer across sports? A preliminary analysis.

PubMed

Smeeton, Nicholas J; Ward, Paul; Williams, A Mark

2004-02-01

The ability to recognize patterns of play is fundamental to performance in team sports. While typically assumed to be domain-specific, pattern recognition skills may transfer from one sport to another if similarities exist in the perceptual features and their relations and/or the strategies used to encode and retrieve relevant information. A transfer paradigm was employed to compare skilled and less skilled soccer, field hockey and volleyball players' pattern recognition skills. Participants viewed structured and unstructured action sequences from each sport, half of which were randomly represented with clips not previously seen. The task was to identify previously viewed action sequences quickly and accurately. Transfer of pattern recognition skill was dependent on the participant's skill, sport practised, nature of the task and degree of structure. The skilled soccer and hockey players were quicker than the skilled volleyball players at recognizing structured soccer and hockey action sequences. Performance differences were not observed on the structured volleyball trials between the skilled soccer, field hockey and volleyball players. The skilled field hockey and soccer players were able to transfer perceptual information or strategies between their respective sports. The less skilled participants' results were less clear. Implications for domain-specific expertise, transfer and diversity across domains are discussed.

Translational simulation: not 'where?' but 'why?' A functional view of in situ simulation.

PubMed

Brazil, Victoria

2017-01-01

Healthcare simulation has been widely adopted for health professional education at all stages of training and practice and across cognitive, procedural, communication and teamwork domains. Recent enthusiasm for in situ simulation-delivered in the real clinical environment-cites improved transfer of knowledge and skills into real-world practice, as well as opportunities to identify latent safety threats and other workplace-specific issues. However, describing simulation type according to place may not be helpful. Instead, I propose the term translational simulation as a functional term for how simulation may be connected directly with health service priorities and patient outcomes, through interventional and diagnostic functions, independent of the location of the simulation activity.

ChpA Controls Twitching Motility and Broadly Affects Gene Expression in the Biological Control Agent Lysobacter enzymogenes.

PubMed

Zhou, Mimi; Shen, Danyu; Xu, Gaoge; Liu, Fengquan; Qian, Guoliang

2017-05-01

Lysobacter enzymogenes (L. enzymogenes) is an agriculturally important Gram-negative bacterium that employs T4P (type IV pili)-driven twitching motility to exhibit its antifungal function. Yet, it is still unclear how this bacterium regulates its twitching motility. Here, by using strain OH11 as the working model organism, we showed that a hybrid two-component system ChpA acts as a positive regulator in controlling twitching motility in L. enzymogenes. ChpA is a hybrid TCS (two-component transduction system) contains 7 domains including those for auto-phosphorylation and phosphate group transfer, as well as a phosphate receiver (REC) domain. Mutation of chpA completely abolished the wild-type twitching motility, as evidenced by the absence of mobile cells at the margin of the mutant colonies. Further studies of domain-deletion and phenotypic characterization reveal that domains responsible for phosphorylation and phosphotransfer, but not the REC domain, were indispensable for ChpA in regulating twitching motility. Transcriptome analyses of the chpA knockout strain indicated that ChpA was extensively involved in controlling expression of a wide variety of genes (totaling 243). The products of these differentially expressed genes were involved in multiple physiological and biological functions in L. enzymogenes. Thus, we have not only identified a new regulator controlling twitching motility in L. enzymogenes, but also provided the first report demonstrating the broad impact of the conserved ChpA in gene regulation in Gram-negative bacteria.

Integrating some mind and brain views of transference: the phenomena.

PubMed

Levin, F M

1997-01-01

Because understanding the underpinnings of transferential learning allows the analyst to more effectively exploit transference in the clinical situation, as well as to advance psychoanalytic theory, the functions and mechanisms of transference phenomena in learning are subjected to an interdisciplinary analysis. Through transference the brain creates hierarchical databases that make emotional sense of the world, especially the world of human relationships. Transference plays a role in defense and resistance clinically; less explored but equally important is the adaptive potential of transference and its effect on an individual's readiness for structural change through the activation of working memory. Most investigators within psychoanalysis have not considered the importance of similarity judgments and memory priming, especially as these help to explain why transference and its proper handling are effective in treatment. Yet there are complex relationships among transference, similarity judgment, and memory priming that tie together psychoanalysis, cognitive psychology, and neurophysiology. Evidence increasingly suggests a relationship between transference and the transfer of knowledge between various content domains (databases) of mind and brain, which is essential to cognitive and emotional learning. There are indications as well that transference decisively facilitates learning readiness ("windows") in general by means of two of its components: free association and spontaneous (self-initiated) activity. The important question of which mind/brain mechanisms motivate transference is not yet understood comprehensively. However, Vygotsky's work on the zone of proximal development (ZPD), M.Stern's teleonomic theory, schema theory, and neural network theory offer further insights into what motivates transference.

Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool

PubMed Central

Zhang, Jian; Frerman, Frank E.; Kim, Jung-Ja P.

2006-01-01

Electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) is a 4Fe4S flavoprotein located in the inner mitochondrial membrane. It catalyzes ubiquinone (UQ) reduction by ETF, linking oxidation of fatty acids and some amino acids to the mitochondrial respiratory chain. Deficiencies in ETF or ETF-QO result in multiple acyl-CoA dehydrogenase deficiency, a human metabolic disease. Crystal structures of ETF-QO with and without bound UQ were determined, and they are essentially identical. The molecule forms a single structural domain. Three functional regions bind FAD, the 4Fe4S cluster, and UQ and are closely packed and share structural elements, resulting in no discrete structural domains. The UQ-binding pocket consists mainly of hydrophobic residues, and UQ binding differs from that of other UQ-binding proteins. ETF-QO is a monotopic integral membrane protein. The putative membrane-binding surface contains an α-helix and a β-hairpin, forming a hydrophobic plateau. The UQ—flavin distance (8.5 Å) is shorter than the UQ—cluster distance (18.8 Å), and the very similar redox potentials of FAD and the cluster strongly suggest that the flavin, not the cluster, transfers electrons to UQ. Two possible electron transfer paths can be envisioned. First, electrons from the ETF flavin semiquinone may enter the ETF-QO flavin one by one, followed by rapid equilibration with the cluster. Alternatively, electrons may enter via the cluster, followed by equilibration between centers. In both cases, when ETF-QO is reduced to a two-electron reduced state (one electron at each redox center), the enzyme is primed to reduce UQ to ubiquinol via FAD. PMID:17050691

Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool.

PubMed

Zhang, Jian; Frerman, Frank E; Kim, Jung-Ja P

2006-10-31

Electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) is a 4Fe4S flavoprotein located in the inner mitochondrial membrane. It catalyzes ubiquinone (UQ) reduction by ETF, linking oxidation of fatty acids and some amino acids to the mitochondrial respiratory chain. Deficiencies in ETF or ETF-QO result in multiple acyl-CoA dehydrogenase deficiency, a human metabolic disease. Crystal structures of ETF-QO with and without bound UQ were determined, and they are essentially identical. The molecule forms a single structural domain. Three functional regions bind FAD, the 4Fe4S cluster, and UQ and are closely packed and share structural elements, resulting in no discrete structural domains. The UQ-binding pocket consists mainly of hydrophobic residues, and UQ binding differs from that of other UQ-binding proteins. ETF-QO is a monotopic integral membrane protein. The putative membrane-binding surface contains an alpha-helix and a beta-hairpin, forming a hydrophobic plateau. The UQ-flavin distance (8.5 A) is shorter than the UQ-cluster distance (18.8 A), and the very similar redox potentials of FAD and the cluster strongly suggest that the flavin, not the cluster, transfers electrons to UQ. Two possible electron transfer paths can be envisioned. First, electrons from the ETF flavin semiquinone may enter the ETF-QO flavin one by one, followed by rapid equilibration with the cluster. Alternatively, electrons may enter via the cluster, followed by equilibration between centers. In both cases, when ETF-QO is reduced to a two-electron reduced state (one electron at each redox center), the enzyme is primed to reduce UQ to ubiquinol via FAD.

Parameter identification for nonlinear aerodynamic systems

NASA Technical Reports Server (NTRS)

Pearson, Allan E.

1991-01-01

Work continues on frequency analysis for transfer function identification, both with respect to the continued development of the underlying algorithms and in the identification study of two physical systems. Some new results of a theoretical nature were recently obtained that lend further insight into the frequency domain interpretation of the research. Progress in each of those areas is summarized. Although not related to the system identification problem, some new results were obtained on the feedback stabilization of linear time lag systems.

A visual approach to efficient analysis and quantification of ductile iron and reinforced sprayed concrete.

PubMed

Fritz, Laura; Hadwiger, Markus; Geier, Georg; Pittino, Gerhard; Gröller, M Eduard

2009-01-01

This paper describes advanced volume visualization and quantification for applications in non-destructive testing (NDT), which results in novel and highly effective interactive workflows for NDT practitioners. We employ a visual approach to explore and quantify the features of interest, based on transfer functions in the parameter spaces of specific application scenarios. Examples are the orientations of fibres or the roundness of particles. The applicability and effectiveness of our approach is illustrated using two specific scenarios of high practical relevance. First, we discuss the analysis of Steel Fibre Reinforced Sprayed Concrete (SFRSpC). We investigate the orientations of the enclosed steel fibres and their distribution, depending on the concrete's application direction. This is a crucial step in assessing the material's behavior under mechanical stress, which is still in its infancy and therefore a hot topic in the building industry. The second application scenario is the designation of the microstructure of ductile cast irons with respect to the contained graphite. This corresponds to the requirements of the ISO standard 945-1, which deals with 2D metallographic samples. We illustrate how the necessary analysis steps can be carried out much more efficiently using our system for 3D volumes. Overall, we show that a visual approach with custom transfer functions in specific application domains offers significant benefits and has the potential of greatly improving and optimizing the workflows of domain scientists and engineers.

Analysis and design of a 3rd order velocity-controlled closed-loop for MEMS vibratory gyroscopes.

PubMed

Wu, Huan-ming; Yang, Hai-gang; Yin, Tao; Jiao, Ji-wei

2013-09-18

The time-average method currently available is limited to analyzing the specific performance of the automatic gain control-proportional and integral (AGC-PI) based velocity-controlled closed-loop in a micro-electro-mechanical systems (MEMS) vibratory gyroscope, since it is hard to solve nonlinear functions in the time domain when the control loop reaches to 3rd order. In this paper, we propose a linearization design approach to overcome this limitation by establishing a 3rd order linear model of the control loop and transferring the analysis to the frequency domain. Order reduction is applied on the built linear model's transfer function by constructing a zero-pole doublet, and therefore mathematical expression of each control loop's performance specification is obtained. Then an optimization methodology is summarized, which reveals that a robust, stable and swift control loop can be achieved by carefully selecting the system parameters following a priority order. Closed-loop drive circuits are designed and implemented using 0.35 μm complementary metal oxide semiconductor (CMOS) process, and experiments carried out on a gyroscope prototype verify the optimization methodology that an optimized stability of the control loop can be achieved by constructing the zero-pole doublet, and disturbance rejection capability (D.R.C) of the control loop can be improved by increasing the integral term.

Type II flavohemoglobin of Mycobacterium smegmatis oxidizes d-lactate and mediate electron transfer.

PubMed

Thakur, Naveen; Kumar, Ashwani; Dikshit, Kanak L

2018-06-01

Two distantly related flavohemoglobins (FHbs), MsFHbI and MsFHbII, having crucial differences in their heme and reductase domains, co-exist in Mycobacterium smegmatis. Function of MsFHbI is associated with nitric-oxide detoxification but physiological relevance of MsFHbII remains unknown. This study unravels some unique spectral and functional characteristics of MsFHbII. Unlike conventional type I FHbs, MsFHbII lacks nitric-oxide dioxygenase and NADH oxidase activities but utilizes d-lactate as an electron donor to mediate electron transfer. MsFHbII carries a d-lactate dehydrogenase type FAD binding motif in its reductase domain and oxidizes d-lactate in a FAD dependent manner to reduce the heme iron, suggesting that the globin is acting as an electron acceptor. Importantly, expression of MsFHbII in Escherichia coli imparted protection under oxidative stress, suggesting its important role in stress management of its host. Since M. smegmatis lacks the gene encoding for d-lactate dehydrogenase and d-lactate is produced during aerobic metabolism and also as a by-product of lipid peroxidation, the ability of MsFHbII to metabolize d-lactate may provide it a unique ability to balance the oxidative stress generated due to accumulation of d-lactate in the cell and at the same time sequester electrons and pass it to the respiratory apparatus. Copyright © 2018 Elsevier B.V. All rights reserved.

Diffusion approximation of the radiative-conductive heat transfer model with Fresnel matching conditions

NASA Astrophysics Data System (ADS)

Chebotarev, Alexander Yu.; Grenkin, Gleb V.; Kovtanyuk, Andrey E.; Botkin, Nikolai D.; Hoffmann, Karl-Heinz

2018-04-01

The paper is concerned with a problem of diffraction type. The study starts with equations of complex (radiative and conductive) heat transfer in a multicomponent domain with Fresnel matching conditions at the interfaces. Applying the diffusion, P1, approximation yields a pair of coupled nonlinear PDEs describing the radiation intensity and temperature for each component of the domain. Matching conditions for these PDEs, imposed at the interfaces between the domain components, are derived. The unique solvability of the obtained problem is proven, and numerical experiments are conducted.

Resolving the negative potential side (n-side) water-accessible proton pathway of F-type ATP synthase by molecular dynamics simulations.

PubMed

Gohlke, Holger; Schlieper, Daniel; Groth, Georg

2012-10-19

The rotation of F(1)F(o)-ATP synthase is powered by the proton motive force across the energy-transducing membrane. The protein complex functions like a turbine; the proton flow drives the rotation of the c-ring of the transmembrane F(o) domain, which is coupled to the ATP-producing F(1) domain. The hairpin-structured c-protomers transport the protons by reversible protonation/deprotonation of a conserved Asp/Glu at the outer transmembrane helix (TMH). An open question is the proton transfer pathway through the membrane at atomic resolution. The protons are thought to be transferred via two half-channels to and from the conserved cAsp/Glu in the middle of the membrane. By molecular dynamics simulations of c-ring structures in a lipid bilayer, we mapped a water channel as one of the half-channels. We also analyzed the suppressor mutant cP24D/E61G in which the functional carboxylate is shifted to the inner TMH of the c-protomers. Current models concentrating on the "locked" and "open" conformations of the conserved carboxylate side chain are unable to explain the molecular function of this mutant. Our molecular dynamics simulations revealed an extended water channel with additional water molecules bridging the distance of the outer to the inner TMH. We suggest that the geometry of the water channel is an important feature for the molecular function of the membrane part of F(1)F(o)-ATP synthase. The inclination of the proton pathway isolates the two half-channels and may contribute to a favorable clockwise rotation in ATP synthesis mode.

Cytochrome P450BM-3 reduces aldehydes to alcohols through a direct hydride transfer

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

Kaspera, Ruediger; Sahele, Tariku; Lakatos, Kyle

Highlights: Black-Right-Pointing-Pointer Cytochrome P450BM-3 reduced aldehydes to alcohols efficiently (k{sub cat} {approx} 25 min{sup -1}). Black-Right-Pointing-Pointer Reduction is a direct hydride transfer from R-NADP{sup 2}H to the carbonyl moiety. Black-Right-Pointing-Pointer P450 domain variants enhance reduction through potential allosteric/redox interactions. Black-Right-Pointing-Pointer Novel reaction will have implications for metabolism of xenobiotics. -- Abstract: Cytochrome P450BM-3 catalyzed the reduction of lipophilic aldehydes to alcohols efficiently. A k{sub cat} of {approx}25 min{sup -1} was obtained for the reduction of methoxy benzaldehyde with wild type P450BM-3 protein which was higher than in the isolated reductase domain (BMR) alone and increased in specific P450-domain variants. Themore » reduction was caused by a direct hydride transfer from preferentially R-NADP{sup 2}H to the carbonyl moiety of the substrate. Weak substrate-P450-binding of the aldehyde, turnover with the reductase domain alone, a deuterium incorporation in the product from NADP{sup 2}H but not D{sub 2}O, and no inhibition by imidazole suggests the reductase domain of P450BM-3 as the potential catalytic site. However, increased aldehyde reduction by P450 domain variants (P450BM-3 F87A T268A) may involve allosteric or redox mechanistic interactions between heme and reductase domains. This is a novel reduction of aldehydes by P450BM-3 involving a direct hydride transfer and could have implications for the metabolism of endogenous substrates or xenobiotics.« less

Learning Factors Transfer Analysis: Using Learning Curve Analysis to Automatically Generate Domain Models

ERIC Educational Resources Information Center

Pavlik, Philip I. Jr.; Cen, Hao; Koedinger, Kenneth R.

2009-01-01

This paper describes a novel method to create a quantitative model of an educational content domain of related practice item-types using learning curves. By using a pairwise test to search for the relationships between learning curves for these item-types, we show how the test results in a set of pairwise transfer relationships that can be…

Functional role of TRIM E3 ligase oligomerization and regulation of catalytic activity.

PubMed

Koliopoulos, Marios G; Esposito, Diego; Christodoulou, Evangelos; Taylor, Ian A; Rittinger, Katrin

2016-06-01

TRIM E3 ubiquitin ligases regulate a wide variety of cellular processes and are particularly important during innate immune signalling events. They are characterized by a conserved tripartite motif in their N-terminal portion which comprises a canonical RING domain, one or two B-box domains and a coiled-coil region that mediates ligase dimerization. Self-association via the coiled-coil has been suggested to be crucial for catalytic activity of TRIMs; however, the precise molecular mechanism underlying this observation remains elusive. Here, we provide a detailed characterization of the TRIM ligases TRIM25 and TRIM32 and show how their oligomeric state is linked to catalytic activity. The crystal structure of a complex between the TRIM25 RING domain and an ubiquitin-loaded E2 identifies the structural and mechanistic features that promote a closed E2~Ub conformation to activate the thioester for ubiquitin transfer allowing us to propose a model for the regulation of activity in the full-length protein. Our data reveal an unexpected diversity in the self-association mechanism of TRIMs that might be crucial for their biological function. © 2016 Francis Crick Institute. Published under the terms of the CC BY 4.0 license.

Adaptive model reduction for continuous systems via recursive rational interpolation

NASA Technical Reports Server (NTRS)

Lilly, John H.

1994-01-01

A method for adaptive identification of reduced-order models for continuous stable SISO and MIMO plants is presented. The method recursively finds a model whose transfer function (matrix) matches that of the plant on a set of frequencies chosen by the designer. The algorithm utilizes the Moving Discrete Fourier Transform (MDFT) to continuously monitor the frequency-domain profile of the system input and output signals. The MDFT is an efficient method of monitoring discrete points in the frequency domain of an evolving function of time. The model parameters are estimated from MDFT data using standard recursive parameter estimation techniques. The algorithm has been shown in simulations to be quite robust to additive noise in the inputs and outputs. A significant advantage of the method is that it enables a type of on-line model validation. This is accomplished by simultaneously identifying a number of models and comparing each with the plant in the frequency domain. Simulations of the method applied to an 8th-order SISO plant and a 10-state 2-input 2-output plant are presented. An example of on-line model validation applied to the SISO plant is also presented.

Three-dimensional structure of human electron transfer flavoprotein to 2.1-Å resolution

PubMed Central

Roberts, David L.; Frerman, Frank E.; Kim, Jung-Ja P.

1996-01-01

Mammalian electron transfer flavoproteins (ETF) are heterodimers containing a single equivalent of flavin adenine dinucleotide (FAD). They function as electron shuttles between primary flavoprotein dehydrogenases involved in mitochondrial fatty acid and amino acid catabolism and the membrane-bound electron transfer flavoprotein ubiquinone oxidoreductase. The structure of human ETF solved to 2.1-Å resolution reveals that the ETF molecule is comprised of three distinct domains: two domains are contributed by the α subunit and the third domain is made up entirely by the β subunit. The N-terminal portion of the α subunit and the majority of the β subunit have identical polypeptide folds, in the absence of any sequence homology. FAD lies in a cleft between the two subunits, with most of the FAD molecule residing in the C-terminal portion of the α subunit. Alignment of all the known sequences for the ETF α subunits together with the putative FixB gene product shows that the residues directly involved in FAD binding are conserved. A hydrogen bond is formed between the N5 of the FAD isoalloxazine ring and the hydroxyl side chain of αT266, suggesting why the pathogenic mutation, αT266M, affects ETF activity in patients with glutaric acidemia type II. Hydrogen bonds between the 4′-hydroxyl of the ribityl chain of FAD and N1 of the isoalloxazine ring, and between αH286 and the C2-carbonyl oxygen of the isoalloxazine ring, may play a role in the stabilization of the anionic semiquinone. With the known structure of medium chain acyl-CoA dehydrogenase, we hypothesize a possible structure for docking the two proteins. PMID:8962055

Discriminative Transfer Subspace Learning via Low-Rank and Sparse Representation.

PubMed

Xu, Yong; Fang, Xiaozhao; Wu, Jian; Li, Xuelong; Zhang, David

2016-02-01

In this paper, we address the problem of unsupervised domain transfer learning in which no labels are available in the target domain. We use a transformation matrix to transfer both the source and target data to a common subspace, where each target sample can be represented by a combination of source samples such that the samples from different domains can be well interlaced. In this way, the discrepancy of the source and target domains is reduced. By imposing joint low-rank and sparse constraints on the reconstruction coefficient matrix, the global and local structures of data can be preserved. To enlarge the margins between different classes as much as possible and provide more freedom to diminish the discrepancy, a flexible linear classifier (projection) is obtained by learning a non-negative label relaxation matrix that allows the strict binary label matrix to relax into a slack variable matrix. Our method can avoid a potentially negative transfer by using a sparse matrix to model the noise and, thus, is more robust to different types of noise. We formulate our problem as a constrained low-rankness and sparsity minimization problem and solve it by the inexact augmented Lagrange multiplier method. Extensive experiments on various visual domain adaptation tasks show the superiority of the proposed method over the state-of-the art methods. The MATLAB code of our method will be publicly available at http://www.yongxu.org/lunwen.html.

The topogenic function of S4 promotes membrane insertion of the voltage-sensor domain in the KvAP channel.

PubMed

Mishima, Eriko; Sato, Yoko; Nanatani, Kei; Hoshi, Naomi; Lee, Jong-Kook; Schiller, Nina; von Heijne, Gunnar; Sakaguchi, Masao; Uozumi, Nobuyuki

2016-12-01

Voltage-dependent K + (K V ) channels control K + permeability in response to shifts in the membrane potential. Voltage sensing in K V channels is mediated by the positively charged transmembrane domain S4. The best-characterized K V channel, KvAP, lacks the distinct hydrophilic region corresponding to the S3-S4 extracellular loop that is found in other K + channels. In the present study, we evaluated the topogenic properties of the transmembrane regions within the voltage-sensing domain in KvAP. S3 had low membrane insertion activity, whereas S4 possessed a unique type-I signal anchor (SA-I) function, which enabled it to insert into the membrane by itself. S4 was also found to function as a stop-transfer signal for retention in the membrane. The length and structural nature of the extracellular S3-S4 loop affected the membrane insertion of S3 and S4, suggesting that S3 membrane insertion was dependent on S4. Replacement of charged residues within the transmembrane regions with residues of opposite charge revealed that Asp 72 in S2 and Glu 93 in S3 contributed to membrane insertion of S3 and S4, and increased the stability of S4 in the membrane. These results indicate that the SA-I function of S4, unique among K + channels studied to date, promotes the insertion of S3 into the membrane, and that the charged residues essential for voltage sensing contribute to the membrane-insertion of the voltage sensor domain in KvAP. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Efficient visibility encoding for dynamic illumination in direct volume rendering.

PubMed

Kronander, Joel; Jönsson, Daniel; Löw, Joakim; Ljung, Patric; Ynnerman, Anders; Unger, Jonas

2012-03-01

We present an algorithm that enables real-time dynamic shading in direct volume rendering using general lighting, including directional lights, point lights, and environment maps. Real-time performance is achieved by encoding local and global volumetric visibility using spherical harmonic (SH) basis functions stored in an efficient multiresolution grid over the extent of the volume. Our method enables high-frequency shadows in the spatial domain, but is limited to a low-frequency approximation of visibility and illumination in the angular domain. In a first pass, level of detail (LOD) selection in the grid is based on the current transfer function setting. This enables rapid online computation and SH projection of the local spherical distribution of visibility information. Using a piecewise integration of the SH coefficients over the local regions, the global visibility within the volume is then computed. By representing the light sources using their SH projections, the integral over lighting, visibility, and isotropic phase functions can be efficiently computed during rendering. The utility of our method is demonstrated in several examples showing the generality and interactive performance of the approach.

Improved spatial resolution of luminescence images acquired with a silicon line scanning camera

NASA Astrophysics Data System (ADS)

Teal, Anthony; Mitchell, Bernhard; Juhl, Mattias K.

2018-04-01

Luminescence imaging is currently being used to provide spatially resolved defect in high volume silicon solar cell production. One option to obtain the high throughput required for on the fly detection is the use a silicon line scan cameras. However, when using a silicon based camera, the spatial resolution is reduced as a result of the weakly absorbed light scattering within the camera's chip. This paper address this issue by applying deconvolution from a measured point spread function. This paper extends the methods for determining the point spread function of a silicon area camera to a line scan camera with charge transfer. The improvement in resolution is quantified in the Fourier domain and in spatial domain on an image of a multicrystalline silicon brick. It is found that light spreading beyond the active sensor area is significant in line scan sensors, but can be corrected for through normalization of the point spread function. The application of this method improves the raw data, allowing effective detection of the spatial resolution of defects in manufacturing.

Same But Different: FIM Summary Scores May Mask Variability in Physical Functioning Profiles.

PubMed

Fisher, Steve R; Middleton, Addie; Graham, James E; Ottenbacher, Kenneth J

2018-02-08

To examine how similar summary scores of physical functioning using the FIM can represent different patient clinical profiles. Retrospective cohort study. Inpatient rehabilitation facilities. Medicare fee-for-service beneficiaries (N=765,441) discharged from inpatient rehabilitation. Not applicable. We used patients' scores on items of the FIM to quantify their level of independence on both self-care and mobility domains. We then identified patients as requiring "no physical assistance" at discharge from inpatient rehabilitation by using a rule and score-based approach. In those patients with FIM self-care and mobility summary scores suggesting no physical assistance needed, we found that physical assistance was in fact needed frequently in bathroom-related activities (eg, continence, toilet and tub transfers, hygiene, clothes management) and with stairs. It was not uncommon for actual performance to be lower than what may be suggested by a summary score of those domains. Further research is needed to create clinically meaningful descriptions of summary scores from combined performances on individual items of physical functioning. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Local geological dust in the area of Rome (Italy): linking mineral composition, size distribution and optical properties to radiative transfer modelling

NASA Astrophysics Data System (ADS)

Pietrodangelo, Adriana; Salzano, Roberto; Bassani, Cristiana; Pareti, Salvatore; Perrino, Cinzia

2015-04-01

Airborne mineral dust plays a key role in the energy balance of the Earth - atmosphere coupled system. The microphysical and optical properties of dust drive the direct radiative effects and are in turn influenced by the dust mineralogical composition. The latter varies largely, depending on the geology of the source region. Knowledge gaps still exist about relationships between the scattering and absorption of solar and terrestrial radiation by mineral dust and its mineralogical, size distribution and particle morphology features; this also affects the reliability of radiative transfer (RT) modelling estimates (Hansell et al., 2011). In this study, these relationships were investigated focusing on the crustal suspended PM10 dust, sourced from outcropping rocks of the local geological domains around Rome (Latium, Italy). The mineral composition variability of the Latium rocks ranges from the silicate-dominated (volcanics domain) to the calcite-dominated (travertine), through lithological materials composed in different proportions by silicates, silica and calcite, mainly (limestone series, siliciclastic series) (Cosentino et al., 2009). This peculiarity of the Latium region was thus exploited to investigate the behavior of the size distribution, optical properties and radiative transfer at BOA (Bottom Of Atmosphere) of the suspended dust PM10 fraction with the variability of mineral composition. Elemental source profiles of the same dust samples were previously determined (Pietrodangelo et al., 2013). A multi-faceted analysis was performed, and outcomes from the following approaches were merged: individual-particle scanning electron microscopy combined with X-ray energy-dispersive microanalysis (SEM XEDS), bulk mineralogical analysis by X-ray diffraction (XRD), size distribution fit of the individual-particle data set and modelling of the dust optical and radiative properties. To this aim, the 6SV atmospheric radiative transfer code (Kotchenova et al., 2008; Vermote et al., 1997) was employed, which computes aerosol optical properties (single-scattering albedo, asymmetry parameter, extinction coefficient, scattering coefficient, phase function) by the Mie Theory, and simulates the downward flux at BOA (FdBOA) by solving the radiative transfer equation. Conditions of dryness and of spherical particle shape were applied to all parts of this work. The size distribution fitting to the log-normal function appears unimodal, both for the volcanics and travertine domains, the first showing coarser mode than the latter. Volume distributions of quartz, feldspar, kaolinite and calcite fall in the coarse fraction, showing maximum around 5µm (aerodynamic diameter); differences in the curve height suggest particle density variety among mineral species. The single-scattering albedo highlights the weak absorption of travertine, with respect to volcanics, along the visible and Near-InfraRed (NIR) spectral domain. The asymmetry parameter indicates that the volcanics dust appears composed by particles with highly forward scattering, mainly in the Near-InfraRed (NIR) spectral domain, while the travertine shows more isotropic particles. Finally, both volcanics and travertine dusts leave the direct component of FdBOA unchanged, while the diffuse component depends strongly on the mineral composition. Hansell, R.A., et al. (2011), Atmos. Chem. Phys. Cosentino, D., et al. (2009), Quaternary Research Pietrodangelo, A., et al. (2013), Atmos. Env. Kotchenova, S.Y., et al. (2008), Appl. Optics Vermote, E.F., et al. (1997), IEEE Trans. Geosci. Remote Sens.

Defining functional distance using manifold embeddings of gene ontology annotations

PubMed Central

Lerman, Gilad; Shakhnovich, Boris E.

2007-01-01

Although rigorous measures of similarity for sequence and structure are now well established, the problem of defining functional relationships has been particularly daunting. Here, we present several manifold embedding techniques to compute distances between Gene Ontology (GO) functional annotations and consequently estimate functional distances between protein domains. To evaluate accuracy, we correlate the functional distance to the well established measures of sequence, structural, and phylogenetic similarities. Finally, we show that manual classification of structures into folds and superfamilies is mirrored by proximity in the newly defined function space. We show how functional distances place structure–function relationships in biological context resulting in insight into divergent and convergent evolution. The methods and results in this paper can be readily generalized and applied to a wide array of biologically relevant investigations, such as accuracy of annotation transference, the relationship between sequence, structure, and function, or coherence of expression modules. PMID:17595300

Recombination–deletion between homologous cassettes in retrovirus is suppressed via a strategy of degenerate codon substitution

PubMed Central

Im, Eung Jun; Bais, Anthony J; Yang, Wen; Ma, Qiangzhong; Guo, Xiuyang; Sepe, Steven M; Junghans, Richard P

2014-01-01

Transduction and expression procedures in gene therapy protocols may optimally transfer more than a single gene to correct a defect and/or transmit new functions to recipient cells or organisms. This may be accomplished by transduction with two (or more) vectors, or, more efficiently, in a single vector. Occasionally, it may be useful to coexpress homologous genes or chimeric proteins with regions of shared homology. Retroviridae include the dominant vector systems for gene transfer (e.g., gamma-retro and lentiviruses) and are capable of such multigene expression. However, these same viruses are known for efficient recombination–deletion when domains are duplicated within the viral genome. This problem can be averted by resorting to two-vector strategies (two-chain two-vector), but at a penalty to cost, convenience, and efficiency. Employing a chimeric antigen receptor system as an example, we confirm that coexpression of two genes with homologous domains in a single gamma-retroviral vector (two-chain single-vector) leads to recombination–deletion between repeated sequences, excising the equivalent of one of the chimeric antigen receptors. Here, we show that a degenerate codon substitution strategy in the two-chain single-vector format efficiently suppressed intravector deletional loss with rescue of balanced gene coexpression by minimizing sequence homology between repeated domains and preserving the final protein sequence. PMID:25419532

Heat transfer enhancement and pumping power optimization using CuO-water nanofluid through rectangular corrugated pipe

NASA Astrophysics Data System (ADS)

Salehin, Musfequs; Ehsan, Mohammad Monjurul; Islam, A. K. M. Sadrul

2017-06-01

Heat transfer enhancement by corrugation in fluid domain is a popular method. The rate of improvement is more when it is used highly thermal conductive fluid as heating or cooling medium. In this present study, heat transfer augmentation was investigated numerically by implementing corrugation in the fluid domain and nanofluid as the base fluid in the turbulent forced convection regime. Finite volume method (FVM) was applied to solve the continuity, momentum and energy equations. All the numerical simulations were considered for single phase flow. A rectangle corrugated pipe with 5000 W/m2 constant heat flux subjected to the corrugated wall was considered as the fluid domain. In the range of Reynolds number 15000 to 40000, thermo-physical and hydrodynamic behavior was investigated by using CuO-water nanofluid from 1% to 5% volume fraction as the base fluid through the corrugated fluid domain. Corrugation justification was performed by changing the amplitude of the corrugation and the corrugation wave length for obtaining the increased heat transfer rate with minimum pumping power. For using CuO-water nanofluid, augmentation was also found more in the rectangle corrugated pipe both in heat transfer and pumping power requirement with the increase of Reynolds number and the volume fraction of nanofluid. For the increased pumping power, optimization of pumping power by using nanofluid was also performed for economic finding.

Activity Augmentation of Amphioxus Peptidoglycan Recognition Protein BbtPGRP3 via Fusion with a Chitin Binding Domain

PubMed Central

Wang, Wen-Jie; Cheng, Wang; Luo, Ming; Yan, Qingyu; Yu, Hong-Mei; Li, Qiong; Cao, Dong-Dong; Huang, Shengfeng; Xu, Anlong; Mariuzza, Roy A.; Chen, Yuxing; Zhou, Cong-Zhao

2015-01-01

Peptidoglycan recognition proteins (PGRPs), which have been identified in most animals, are pattern recognition molecules that involve antimicrobial defense. Resulting from extraordinary expansion of innate immune genes, the amphioxus encodes many PGRPs of diverse functions. For instance, three isoforms of PGRP encoded by Branchiostoma belcheri tsingtauense, termed BbtPGRP1~3, are fused with a chitin binding domain (CBD) at the N-terminus. Here we report the 2.7 Å crystal structure of BbtPGRP3, revealing an overall structure of an N-terminal hevein-like CBD followed by a catalytic PGRP domain. Activity assays combined with site-directed mutagenesis indicated that the individual PGRP domain exhibits amidase activity towards both DAP-type and Lys-type peptidoglycans (PGNs), the former of which is favored. The N-terminal CBD not only has the chitin-binding activity, but also enables BbtPGRP3 to gain a five-fold increase of amidase activity towards the Lys-type PGNs, leading to a significantly broadened substrate spectrum. Together, we propose that modular evolution via domain shuffling combined with gene horizontal transfer makes BbtPGRP1~3 novel PGRPs of augmented catalytic activity and broad recognition spectrum. PMID:26479246

The C-terminal domain of Tetrahymena thermophila telomerase holoenzyme protein p65 induces multiple structural changes in telomerase RNA

PubMed Central

Akiyama, Benjamin M.; Loper, John; Najarro, Kevin; Stone, Michael D.

2012-01-01

The unique cellular activity of the telomerase reverse transcriptase ribonucleoprotein (RNP) requires proper assembly of protein and RNA components into a functional complex. In the ciliate model organism Tetrahymena thermophila, the La-domain protein p65 is required for in vivo assembly of telomerase. Single-molecule and biochemical studies have shown that p65 promotes efficient RNA assembly with the telomerase reverse transcriptase (TERT) protein, in part by inducing a bend in the conserved stem IV region of telomerase RNA (TER). The domain architecture of p65 consists of an N-terminal domain, a La-RRM motif, and a C-terminal domain (CTD). Using single-molecule Förster resonance energy transfer (smFRET), we demonstrate the p65CTD is necessary for the RNA remodeling activity of the protein and is sufficient to induce a substantial conformational change in stem IV of TER. Moreover, nuclease protection assays directly map the site of p65CTD interaction to stem IV and reveal that, in addition to bending stem IV, p65 binding reorganizes nucleotides that comprise the low-affinity TERT binding site within stem–loop IV. PMID:22315458

Frequency domain system identification of helicopter rotor dynamics incorporating models with time periodic coefficients

NASA Astrophysics Data System (ADS)

Hwang, Sunghwan

1997-08-01

One of the most prominent features of helicopter rotor dynamics in forward flight is the periodic coefficients in the equations of motion introduced by the rotor rotation. The frequency response characteristics of such a linear time periodic system exhibits sideband behavior, which is not the case for linear time invariant systems. Therefore, a frequency domain identification methodology for linear systems with time periodic coefficients was developed, because the linear time invariant theory cannot account for sideband behavior. The modulated complex Fourier series was introduced to eliminate the smearing effect of Fourier series expansions of exponentially modulated periodic signals. A system identification theory was then developed using modulated complex Fourier series expansion. Correlation and spectral density functions were derived using the modulated complex Fourier series expansion for linear time periodic systems. Expressions of the identified harmonic transfer function were then formulated using the spectral density functions both with and without additive noise processes at input and/or output. A procedure was developed to identify parameters of a model to match the frequency response characteristics between measured and estimated harmonic transfer functions by minimizing an objective function defined in terms of the trace of the squared frequency response error matrix. Feasibility was demonstrated by the identification of the harmonic transfer function and parameters for helicopter rigid blade flapping dynamics in forward flight. This technique is envisioned to satisfy the needs of system identification in the rotating frame, especially in the context of individual blade control. The technique was applied to the coupled flap-lag-inflow dynamics of a rigid blade excited by an active pitch link. The linear time periodic technique results were compared with the linear time invariant technique results. Also, the effect of noise processes and initial parameter guess on the identification procedure were investigated. To study the effect of elastic modes, a rigid blade with a trailing edge flap excited by a smart actuator was selected and system parameters were successfully identified, but with some expense of computational storage and time. Conclusively, the linear time periodic technique substantially improved the identified parameter accuracy compared to the linear time invariant technique. Also, the linear time periodic technique was robust to noises and initial guess of parameters. However, an elastic mode of higher frequency relative to the system pumping frequency tends to increase the computer storage requirement and computing time.

Allostery in the ferredoxin protein motif does not involve a conformational switch.

PubMed

Nechushtai, Rachel; Lammert, Heiko; Michaeli, Dorit; Eisenberg-Domovich, Yael; Zuris, John A; Luca, Maria A; Capraro, Dominique T; Fish, Alex; Shimshon, Odelia; Roy, Melinda; Schug, Alexander; Whitford, Paul C; Livnah, Oded; Onuchic, José N; Jennings, Patricia A

2011-02-08

Regulation of protein function via cracking, or local unfolding and refolding of substructures, is becoming a widely recognized mechanism of functional control. Oftentimes, cracking events are localized to secondary and tertiary structure interactions between domains that control the optimal position for catalysis and/or the formation of protein complexes. Small changes in free energy associated with ligand binding, phosphorylation, etc., can tip the balance and provide a regulatory functional switch. However, understanding the factors controlling function in single-domain proteins is still a significant challenge to structural biologists. We investigated the functional landscape of a single-domain plant-type ferredoxin protein and the effect of a distal loop on the electron-transfer center. We find the global stability and structure are minimally perturbed with mutation, whereas the functional properties are altered. Specifically, truncating the L1,2 loop does not lead to large-scale changes in the structure, determined via X-ray crystallography. Further, the overall thermal stability of the protein is only marginally perturbed by the mutation. However, even though the mutation is distal to the iron-sulfur cluster (∼20 Å), it leads to a significant change in the redox potential of the iron-sulfur cluster (57 mV). Structure-based all-atom simulations indicate correlated dynamical changes between the surface-exposed loop and the iron-sulfur cluster-binding region. Our results suggest intrinsic communication channels within the ferredoxin fold, composed of many short-range interactions, lead to the propagation of long-range signals. Accordingly, protein interface interactions that involve L1,2 could potentially signal functional changes in distal regions, similar to what is observed in other allosteric systems.

Output-Sensitive Construction of Reeb Graphs.

PubMed

Doraiswamy, H; Natarajan, V

2012-01-01

The Reeb graph of a scalar function represents the evolution of the topology of its level sets. This paper describes a near-optimal output-sensitive algorithm for computing the Reeb graph of scalar functions defined over manifolds or non-manifolds in any dimension. Key to the simplicity and efficiency of the algorithm is an alternate definition of the Reeb graph that considers equivalence classes of level sets instead of individual level sets. The algorithm works in two steps. The first step locates all critical points of the function in the domain. Critical points correspond to nodes in the Reeb graph. Arcs connecting the nodes are computed in the second step by a simple search procedure that works on a small subset of the domain that corresponds to a pair of critical points. The paper also describes a scheme for controlled simplification of the Reeb graph and two different graph layout schemes that help in the effective presentation of Reeb graphs for visual analysis of scalar fields. Finally, the Reeb graph is employed in four different applications-surface segmentation, spatially-aware transfer function design, visualization of interval volumes, and interactive exploration of time-varying data.

Current-induced domain wall motion in permalloy nanowires with a rectangular cross-section

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

Ai, J. H.; Miao, B. F.; Sun, L.

2011-11-01

We performed micromagnetic simulations of the current-induced domain wall motion in permalloy nanowires with rectangular cross-section. In the absence of the nonadiabatic spin-transfer term, a threshold current, J{sub c} is required to drive the domain wall moving continuously. We find that J{sub c} is proportional to the maximum cross product of the demagnetization field and magnetization orientation of the domain wall and the domain wall width. With varying both the wire thickness and width, a minimum threshold current in the order of 10{sup 6} A/cm{sup 2} is obtained when the thickness is equivalent to the wire width. With the nonadiabaticmore » spin-transfer term, the calculated domain wall velocity {nu} equals to the adiabatic spin transfer velocity u when the current is far above the Walker limit J{sub w}. Below J{sub w}, {nu}=({beta}/{alpha})u, where {beta} is the nonadiabatic parameter and {alpha} is the damping factor. For different {beta}, we find the Walker limit can be scaled as J{sub w}=({alpha}/{beta}-{alpha})J{sub c}. Our simulations agree well with the one dimensional analytical calculation, suggesting the findings are the general behaviors of the systems in this particular geometry.« less

The Molybdenum Cofactor Biosynthetic Protein Cnx1 Complements Molybdate-Repairable Mutants, Transfers Molybdenum to the Metal Binding Pterin, and Is Associated with the Cytoskeleton

PubMed Central

Schwarz, Günter; Schulze, Jutta; Bittner, Florian; Eilers, Thomas; Kuper, Jochen; Bollmann, Gabriele; Nerlich, Andrea; Brinkmann, Henner; Mendel, Ralf R.

2000-01-01

Molybdenum (Mo) plays an essential role in the active site of all eukaryotic Mo-containing enzymes. In plants, Mo enzymes are important for nitrate assimilation, phytohormone synthesis, and purine catabolism. Mo is bound to a unique metal binding pterin (molybdopterin [MPT]), thereby forming the active Mo cofactor (Moco), which is highly conserved in eukaryotes, eubacteria, and archaebacteria. Here, we describe the function of the two-domain protein Cnx1 from Arabidopsis in the final step of Moco biosynthesis. Cnx1 is constitutively expressed in all organs and in plants grown on different nitrogen sources. Mo-repairable cnxA mutants from Nicotiana plumbaginifolia accumulate MPT and show altered Cnx1 expression. Transformation of cnxA mutants and the corresponding Arabidopsis chl-6 mutant with cnx1 cDNA resulted in functional reconstitution of their Moco deficiency. We also identified a point mutation in the Cnx1 E domain of Arabidopsis chl-6 that causes the molybdate-repairable phenotype. Recombinant Cnx1 protein is capable of synthesizing Moco. The G domain binds and activates MPT, whereas the E domain is essential for activating Mo. In addition, Cnx1 binds to the cytoskeleton in the same way that its mammalian homolog gephyrin does in neuronal cells, which suggests a hypothetical model for anchoring the Moco-synthetic machinery by Cnx1 in plant cells. PMID:11148290

Hybrid proline-rich proteins: novel players in plant cell elongation?

PubMed Central

Dvořáková, Lenka; Srba, Miroslav; Opatrny, Zdenek; Fischer, Lukas

2012-01-01

Background and Aims Hybrid proline-rich proteins (HyPRPs) represent a large family of putative cell-wall proteins characterized by the presence of a variable N-terminal domain and a conserved C-terminal domain that is related to non-specific lipid transfer proteins. The function of HyPRPs remains unclear, but their widespread occurrence and abundant expression patterns indicate that they may be involved in a basic cellular process. Methods To elucidate the cellular function of HyPRPs, we modulated the expression of three HyPRP genes in tobacco (Nicotiana tabacum) BY-2 cell lines and in potato (Solanum tuberosum) plants. Key Results In BY-2 lines, over-expression of the three HyPRP genes with different types of N-terminal domains resulted in similar phenotypic changes, namely increased cell elongation, both in suspension culture and on solid media where the over-expression resulted in enhanced calli size. The over-expressing cells showed increased plasmolysis in a hypertonic mannitol solution and accelerated rate of protoplast release, suggesting loosening of the cell walls. In contrast to BY-2 lines, no phenotypic changes were observed in potato plants over-expressing the same or analogous HyPRP genes, presumably due to more complex compensatory mechanisms in planta. Conclusions Based on the results from BY-2 lines, we propose that HyPRPs, more specifically their C-terminal domains, represent a novel group of proteins involved in cell expansion. PMID:22028464

Prion-specific Hsp40 function: The role of the auxilin homolog Swa2

PubMed Central

Oliver, Emily E.; Troisi, Elizabeth M.; Hines, Justin K.

2017-01-01

ABSTRACT Yeast prions are protein-based genetic elements that propagate through cell populations via cytosolic transfer from mother to daughter cell. Molecular chaperone proteins including Hsp70, the Hsp40/J-protein Sis1, and Hsp104 are required for continued prion propagation, however the specific requirements of chaperone proteins differ for various prions. We recently reported that Swa2, the yeast homolog of the mammalian protein auxilin, is specifically required for the propagation of the prion [URE3].1 [URE3] propagation requires both a functional J-domain and the tetratricopeptide repeat (TPR) domain of Swa2, but does not require Swa2 clathrin binding. We concluded that the TPR domain determines the specificity of the genetic interaction between Swa2 and [URE3], and that this domain likely interacts with one or more proteins with a C-terminal EEVD motif. Here we extend that analysis to incorporate additional data that supports this hypothesis. We also present new data eliminating Hsp104 as the relevant Swa2 binding partner and discuss our findings in the context of other recent work involving Hsp90. Based on these findings, we propose a new model for Swa2's involvement in [URE3] propagation in which Swa2 and Hsp90 mediate the formation of a multi-protein complex that increases the number of sites available for Hsp104 disaggregation. PMID:28574745

Pulse analysis of acoustic emission signals

NASA Technical Reports Server (NTRS)

Houghton, J. R.; Packman, P. F.

1977-01-01

A method for the signature analysis of pulses in the frequency domain and the time domain is presented. Fourier spectrum, Fourier transfer function, shock spectrum and shock spectrum ratio were examined in the frequency domain analysis and pulse shape deconvolution was developed for use in the time domain analysis. Comparisons of the relative performance of each analysis technique are made for the characterization of acoustic emission pulses recorded by a measuring system. To demonstrate the relative sensitivity of each of the methods to small changes in the pulse shape, signatures of computer modeled systems with analytical pulses are presented. Optimization techniques are developed and used to indicate the best design parameter values for deconvolution of the pulse shape. Several experiments are presented that test the pulse signature analysis methods on different acoustic emission sources. These include acoustic emission associated with (a) crack propagation, (b) ball dropping on a plate, (c) spark discharge, and (d) defective and good ball bearings. Deconvolution of the first few micro-seconds of the pulse train is shown to be the region in which the significant signatures of the acoustic emission event are to be found.

Pulse analysis of acoustic emission signals

NASA Technical Reports Server (NTRS)

Houghton, J. R.; Packman, P. F.

1977-01-01

A method for the signature analysis of pulses in the frequency domain and the time domain is presented. Fourier spectrum, Fourier transfer function, shock spectrum and shock spectrum ratio were examined in the frequency domain analysis, and pulse shape deconvolution was developed for use in the time domain analysis. Comparisons of the relative performance of each analysis technique are made for the characterization of acoustic emission pulses recorded by a measuring system. To demonstrate the relative sensitivity of each of the methods to small changes in the pulse shape, signatures of computer modeled systems with analytical pulses are presented. Optimization techniques are developed and used to indicate the best design parameters values for deconvolution of the pulse shape. Several experiments are presented that test the pulse signature analysis methods on different acoustic emission sources. These include acoustic emissions associated with: (1) crack propagation, (2) ball dropping on a plate, (3) spark discharge and (4) defective and good ball bearings. Deconvolution of the first few micro-seconds of the pulse train are shown to be the region in which the significant signatures of the acoustic emission event are to be found.

An exploration of exercise-induced cognitive enhancement and transfer effects to dietary self-control.

PubMed

Lowe, Cassandra J; Kolev, Dimitar; Hall, Peter A

2016-12-01

The primary objective of this study was to examine the effects of aerobic exercise on executive function, specifically inhibitory control, and the transfer to self-control in the dietary domain. It was hypothesized that exercise would enhance inhibitory control, and that this enhancement would facilitate self-control in a laboratory taste test paradigm. Using a crossover design, 51 participants completed counterbalanced sessions of both moderate exercise (experimental condition) and minimal effort walking (control condition) using a treadmill; the intersession interval was 7days. Prior to each exercise bout participants completed a Stroop task. Following each bout participants completed a second Stoop task, as well as a bogus taste test involving three appetitive calorie dense snack foods and two control foods; the amount of each food type consumed during the taste test was covertly measured. Results revealed that moderate exercise significantly improved performance on the Stroop task, and also reduced food consumption during the taste test for appetitive calorie dense snack foods; there was no exercise effect on control food consumption. Exercise-induced gains in Stroop performance mediated the effects of moderate exercise on appetitive snack food consumption. Together these findings provide evidence that a bout of a moderate aerobic exercise can enhance inhibitory control, and support for cross-domain transfer effects to dietary self-control. Copyright © 2016 Elsevier Inc. All rights reserved.

Training self-assessment and task-selection skills to foster self-regulated learning: Do trained skills transfer across domains?

PubMed

Raaijmakers, Steven F; Baars, Martine; Paas, Fred; van Merriënboer, Jeroen J G; van Gog, Tamara

2018-01-01

Students' ability to accurately self-assess their performance and select a suitable subsequent learning task in response is imperative for effective self-regulated learning. Video modeling examples have proven effective for training self-assessment and task-selection skills, and-importantly-such training fostered self-regulated learning outcomes. It is unclear, however, whether trained skills would transfer across domains. We investigated whether skills acquired from training with either a specific, algorithmic task-selection rule or a more general heuristic task-selection rule in biology would transfer to self-regulated learning in math. A manipulation check performed after the training confirmed that both algorithmic and heuristic training improved task-selection skills on the biology problems compared with the control condition. However, we found no evidence that students subsequently applied the acquired skills during self-regulated learning in math. Future research should investigate how to support transfer of task-selection skills across domains.

Training self‐assessment and task‐selection skills to foster self‐regulated learning: Do trained skills transfer across domains?

PubMed Central

Baars, Martine; Paas, Fred; van Merriënboer, Jeroen J. G.; van Gog, Tamara

2018-01-01

Summary Students' ability to accurately self‐assess their performance and select a suitable subsequent learning task in response is imperative for effective self‐regulated learning. Video modeling examples have proven effective for training self‐assessment and task‐selection skills, and—importantly—such training fostered self‐regulated learning outcomes. It is unclear, however, whether trained skills would transfer across domains. We investigated whether skills acquired from training with either a specific, algorithmic task‐selection rule or a more general heuristic task‐selection rule in biology would transfer to self‐regulated learning in math. A manipulation check performed after the training confirmed that both algorithmic and heuristic training improved task‐selection skills on the biology problems compared with the control condition. However, we found no evidence that students subsequently applied the acquired skills during self‐regulated learning in math. Future research should investigate how to support transfer of task‐selection skills across domains. PMID:29610547

Current-induced instability of domain walls in cylindrical nanowires

NASA Astrophysics Data System (ADS)

Wang, Weiwei; Zhang, Zhaoyang; Pepper, Ryan A.; Mu, Congpu; Zhou, Yan; Fangohr, Hans

2018-01-01

We study the current-driven domain wall (DW) motion in cylindrical nanowires using micromagnetic simulations by implementing the Landau-Lifshitz-Gilbert equation with nonlocal spin-transfer torque in a finite difference micromagnetic package. We find that in the presence of DW, Gaussian wave packets (spin waves) will be generated when the charge current is suddenly applied to the system. This effect is excluded when using the local spin-transfer torque. The existence of spin waves emission indicates that transverse domain walls can not move arbitrarily fast in cylindrical nanowires although they are free from the Walker limit. We establish an upper velocity limit for DW motion by analyzing the stability of Gaussian wave packets using the local spin-transfer torque. Micromagnetic simulations show that the stable region obtained by using nonlocal spin-transfer torque is smaller than that by using its local counterpart. This limitation is essential for multiple DWs since the instability of Gaussian wave packets will break the structure of multiple DWs.

STAND, a class of P-loop NTPases including animal and plant regulators of programmed cell death: multiple, complex domain architectures, unusual phyletic patterns, and evolution by horizontal gene transfer.

PubMed

Leipe, Detlef D; Koonin, Eugene V; Aravind, L

2004-10-08

Using sequence profile analysis and sequence-based structure predictions, we define a previously unrecognized, widespread class of P-loop NTPases. The signal transduction ATPases with numerous domains (STAND) class includes the AP-ATPases (animal apoptosis regulators CED4/Apaf-1, plant disease resistance proteins, and bacterial AfsR-like transcription regulators) and NACHT NTPases (e.g. NAIP, TLP1, Het-E-1) that have been studied extensively in the context of apoptosis, pathogen response in animals and plants, and transcriptional regulation in bacteria. We show that, in addition to these well-characterized protein families, the STAND class includes several other groups of (predicted) NTPase domains from diverse signaling and transcription regulatory proteins from bacteria and eukaryotes, and three Archaea-specific families. We identified the STAND domain in several biologically well-characterized proteins that have not been suspected to have NTPase activity, including soluble adenylyl cyclases, nephrocystin 3 (implicated in polycystic kidney disease), and Rolling pebble (a regulator of muscle development); these findings are expected to facilitate elucidation of the functions of these proteins. The STAND class belongs to the additional strand, catalytic E division of P-loop NTPases together with the AAA+ ATPases, RecA/helicase-related ATPases, ABC-ATPases, and VirD4/PilT-like ATPases. The STAND proteins are distinguished from other P-loop NTPases by the presence of unique sequence motifs associated with the N-terminal helix and the core strand-4, as well as a C-terminal helical bundle that is fused to the NTPase domain. This helical module contains a signature GxP motif in the loop between the two distal helices. With the exception of the archaeal families, almost all STAND NTPases are multidomain proteins containing three or more domains. In addition to the NTPase domain, these proteins typically contain DNA-binding or protein-binding domains, superstructure-forming repeats, such as WD40 and TPR, and enzymatic domains involved in signal transduction, including adenylate cyclases and kinases. By analogy to the AAA+ ATPases, it can be predicted that STAND NTPases use the C-terminal helical bundle as a "lever" to transmit the conformational changes brought about by NTP hydrolysis to effector domains. STAND NTPases represent a novel paradigm in signal transduction, whereby adaptor, regulatory switch, scaffolding, and, in some cases, signal-generating moieties are combined into a single polypeptide. The STAND class consists of 14 distinct families, and the evolutionary history of most of these families is riddled with dramatic instances of lineage-specific expansion and apparent horizontal gene transfer. The STAND NTPases are most abundant in developmentally and organizationally complex prokaryotes and eukaryotes. Transfer of genes for STAND NTPases from bacteria to eukaryotes on several occasions might have played a significant role in the evolution of eukaryotic signaling systems.

Experimentally biased model structure of the Hsc70/auxilin complex: Substrate transfer and interdomain structural change

PubMed Central

Gruschus, James M.; Greene, Lois E.; Eisenberg, Evan; Ferretti, James A.

2004-01-01

A model structure of the Hsc70/auxilin complex has been constructed to gain insight into interprotein substrate transfer and ATP hydrolysis induced conformational changes in the multidomain Hsc70 structure. The Hsc70/auxilin system, which is a member of the Hsp70/Hsp40 chaperone system family, uncoats clathrin-coated vesicles in an ATP hydrolysis-driven process. Incorporating previous results from NMR and mutant binding studies, the auxilin J-domain was docked into the Hsc70 ATPase domain lower cleft using rigid backbone/flexible side chain molecular dynamics, and the Hsc70 substrate binding domain was docked by a similar procedure. For comparison, J-domain and substrate binding domain docking sites were obtained by the rigid-body docking programs DOT and ZDOCK, filtered and ranked by the program ClusPro, and relaxed using the same rigid backbone/flexible side chain dynamics. The substrate binding domain sites were assessed in terms of conserved surface complementarity and feasibility in the context of substrate transfer, both for auxilin and another Hsp40 protein, Hsc20. This assessment favors placement of the substrate binding domain near D152 on the ATPase domain surface adjacent to the J-domain invariant HPD segment, with the Hsc70 interdomain linker in the lower cleft. Examining Hsc70 interdomain energetics, we propose that long-range electrostatic interactions, perhaps due to a difference in the pKa values of bound ATP and ADP, could play a major role in the structural change induced by ATP hydrolysis. Interdomain electrostatic interactions also appear to play a role in stimulation of ATPase activity due to J-domain binding and substrate binding by Hsc70. PMID:15273304

A conjugate heat transfer procedure for gas turbine blades.

PubMed

Croce, G

2001-05-01

A conjugate heat transfer procedure, allowing for the use of different solvers on the solid and fluid domain(s), is presented. Information exchange between solid and fluid solution is limited to boundary condition values, and this exchange is carried out at any pseudo-time step. Global convergence rate of the procedure is, thus, of the same order of magnitude of stand-alone computations.

Effects of Three Diagram Instruction Methods on Transfer of Diagram Comprehension Skills: The Critical Role of Inference While Learning

ERIC Educational Resources Information Center

Cromley, Jennifer G.; Bergey, Bradley W.; Fitzhugh, Shannon; Newcombe, Nora; Wills, Theodore W.; Shipley, Thomas F.; Tanaka, Jacqueline C.

2013-01-01

Can students be taught to better comprehend the diagrams in their textbooks? Can such teaching transfer to uninstructed diagrams in the same domain or even in a new domain? What methods work best for these goals? Building on previous research showing positive results compared to control groups in both laboratory studies and short-term…

Congenital hypothyroidism mutations affect common folding and trafficking in the α/β-hydrolase fold proteins

PubMed Central

De Jaco, Antonella; Dubi, Noga; Camp, Shelley; Taylor, Palmer

2017-01-01

The α/β-hydrolase fold superfamily of proteins is composed of structurally related members that, despite great diversity in their catalytic, recognition, adhesion and chaperone functions, share a common fold governed by homologous residues and conserved disulfide bridges. Non-synonymous single nucleotide polymorphisms within the α/β-hydrolase fold domain in various family members have been found for congenital endocrine, metabolic and nervous system disorders. By examining the amino acid sequence from the various proteins, mutations were found to be prevalent in conserved residues within the α/β-hydrolase fold of the homologous proteins. This is the case for the thyroglobulin mutations linked to congenital hypothyroidism. To address whether correct folding of the common domain is required for protein export, we inserted the thyroglobulin mutations at homologous positions in two correlated but simpler α/β-hydrolase fold proteins known to be exported to the cell surface: neuroligin3 and acetylcholinesterase. Here we show that these mutations in the cholinesterase homologous region alter the folding properties of the α/β-hydrolase fold domain, which are reflected in defects in protein trafficking, folding and function, and ultimately result in retention of the partially processed proteins in the endoplasmic reticulum. Accordingly, mutations at conserved residues may be transferred amongst homologous proteins to produce common processing defects despite disparate functions, protein complexity and tissue-specific expression of the homologous proteins. More importantly, a similar assembly of the α/β-hydrolase fold domain tertiary structure among homologous members of the superfamily is required for correct trafficking of the proteins to their final destination. PMID:23035660

Deep transfer learning for automatic target classification: MWIR to LWIR

NASA Astrophysics Data System (ADS)

Ding, Zhengming; Nasrabadi, Nasser; Fu, Yun

2016-05-01

Publisher's Note: This paper, originally published on 5/12/2016, was replaced with a corrected/revised version on 5/18/2016. If you downloaded the original PDF but are unable to access the revision, please contact SPIE Digital Library Customer Service for assistance. When dealing with sparse or no labeled data in the target domain, transfer learning shows its appealing performance by borrowing the supervised knowledge from external domains. Recently deep structure learning has been exploited in transfer learning due to its attractive power in extracting effective knowledge through multi-layer strategy, so that deep transfer learning is promising to address the cross-domain mismatch. In general, cross-domain disparity can be resulted from the difference between source and target distributions or different modalities, e.g., Midwave IR (MWIR) and Longwave IR (LWIR). In this paper, we propose a Weighted Deep Transfer Learning framework for automatic target classification through a task-driven fashion. Specifically, deep features and classifier parameters are obtained simultaneously for optimal classification performance. In this way, the proposed deep structures can extract more effective features with the guidance of the classifier performance; on the other hand, the classifier performance is further improved since it is optimized on more discriminative features. Furthermore, we build a weighted scheme to couple source and target output by assigning pseudo labels to target data, therefore we can transfer knowledge from source (i.e., MWIR) to target (i.e., LWIR). Experimental results on real databases demonstrate the superiority of the proposed algorithm by comparing with others.

Gene transfer of extracellular superoxide dismutase reduces arterial pressure in spontaneously hypertensive rats: role of heparin-binding domain.

PubMed

Chu, Yi; Iida, Shinichiro; Lund, Donald D; Weiss, Robert M; DiBona, Gerald F; Watanabe, Yoshimasa; Faraci, Frank M; Heistad, Donald D

2003-03-07

Oxidative stress may contribute to hypertension. The goals of this study were to determine whether extracellular superoxide dismutase (ECSOD) reduces arterial pressure in spontaneously hypertensive rats (SHR) and whether its heparin-binding domain (HBD), which is responsible for cellular binding, is necessary for the function of ECSOD. Three days after intravenous injection of an adenoviral vector expressing human ECSOD (AdECSOD), mean arterial pressure (MAP) decreased from 165+/-4 mm Hg (mean+/-SE, n=7) to 124+/-3 mm Hg (n=7) in adult anesthetized SHR (P<0.01) but was not altered in normotensive Wistar-Kyoto rats. Cardiac output was not changed in SHR 3 days after AdECSOD. Gene transfer of ECSOD with deletion of the HBD (AdECSODDeltaHBD) had no effect on SHR MAP, even though plasma SOD activity was greater after AdECSODDeltaHBD than after AdECSOD. Immunohistochemistry revealed intense staining for ECSOD in blood vessels and kidneys after AdECSOD but not after AdECSODDeltaHBD. Impaired relaxation of the carotid artery to acetylcholine in SHR was significantly improved after AdECSOD. Cumulative sodium balance in SHR was reduced by AdECSOD compared with AdECSODDeltaHBD. Gene transfer of ECSOD also reduced MAP in conscious SHR, although the effect was not as profound as in anesthetized SHR. In summary, gene transfer of ECSOD, with a strict requirement for its HBD, reduces systemic vascular resistance and arterial pressure in a genetic model of hypertension. This reduction in arterial pressure may be mediated by vasomotor and/or renal mechanisms.

Density functional theory studies on molecular structure and vibrational spectra of NLO crystal L-phenylalanine phenylalanium nitrate for THz application

NASA Astrophysics Data System (ADS)

Amalanathan, M.; Hubert Joe, I.; Rastogi, V. K.

2011-12-01

Molecular structure, FT-IR and Raman spectra of L-phenylalanine phenylalanium nitrate have been investigated using density functional theory calculation. The polarizability and hyperpolarizability value of the crystal is also calculated. Natural bond orbital analysis confirms the presence of intramolecular charge transfer and the hydrogen bonding interaction. Simultaneous activation of ring C sbnd C stretching modes shows the non-centrosymmetric symmetry. Terahertz time-domain spectroscopy has been used to detect the absorption spectra in the frequency range from 0.05 to 1.3 THz. Theoretically predicted β value exhibits the high nonlinear optical activity.

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

Orthologs, paralogs and genome comparisons

NASA Technical Reports Server (NTRS)

Gogarten, J. P.; Olendzenski, L.

1999-01-01

During the past decade, ancient gene duplications were recognized as one of the main forces in the generation of diverse gene families and the creation of new functional capabilities. New tools developed to search data banks for homologous sequences, and an increased availability of reliable three-dimensional structural information led to the recognition that proteins with diverse functions can belong to the same superfamily. Analyses of the evolution of these superfamilies promises to provide insights into early evolution but are complicated by several important evolutionary processes. Horizontal transfer of genes can lead to a vertical spread of innovations among organisms, therefore finding a certain property in some descendants of an ancestor does not guarantee that it was present in that ancestor. Complete or partial gene conversion between duplicated genes can yield phylogenetic trees with several, apparently independent gene duplications, suggesting an often surprising parallelism in the evolution of independent lineages. Additionally, the breakup of domains within a protein and the fusion of domains into multifunctional proteins makes the delineation of superfamilies a task that remains difficult to automate.

Hsp42 is required for sequestration of protein aggregates into deposition sites in Saccharomyces cerevisiae

PubMed Central

Specht, Sebastian; Miller, Stephanie B.M.

2011-01-01

The aggregation of proteins inside cells is an organized process with cytoprotective function. In Saccharomyces cerevisiae, aggregating proteins are spatially sequestered to either juxtanuclear or peripheral sites, which target distinct quality control pathways for refolding and degradation. The cellular machinery driving the sequestration of misfolded proteins to these sites is unknown. In this paper, we show that one of the two small heat shock proteins of yeast, Hsp42, is essential for the formation of peripheral aggregates during physiological heat stress. Hsp42 preferentially localizes to peripheral aggregates but is largely absent from juxtanuclear aggregates, which still form in hsp42Δ cells. Transferring the amino-terminal domain of Hsp42 to Hsp26, which does not participate in aggregate sorting, enables Hsp26 to replace Hsp42 function. Our data suggest that Hsp42 acts via its amino-terminal domain to coaggregate with misfolded proteins and perhaps link such complexes to further sorting factors. PMID:22065637

An analog filter approach to frequency domain fluorescence spectroscopy

DOE PAGES

Trainham, Clifford P.; O'Neill, Mary D.; McKenna, Ian J.

2015-10-01

The rate equations found in frequency domain fluorescence spectroscopy are the same as those found in electronics under analog filter theory. Laplace transform methods are a natural way to solve the equations, and the methods can provide solutions for arbitrary excitation functions. The fluorescence terms can be modeled as circuit components and cascaded with drive and detection electronics to produce a global transfer function. Electronics design tools such as Spicea can be used to model fluorescence problems. In applications, such as remote sensing, where detection electronics are operated at high gain and limited bandwidth, a global modeling of the entiremore » system is important, since the filter terms of the drive and detection electronics affect the measured response of the fluorescence signals. Furthermore, the techniques described here can be used to separate signals from fast and slow fluorophores emitting into the same spectral band, and data collection can be greatly accelerated by means of a frequency comb driver waveform and appropriate signal processing of the response.« less

Model-Driven Approach for Body Area Network Application Development.

PubMed

Venčkauskas, Algimantas; Štuikys, Vytautas; Jusas, Nerijus; Burbaitė, Renata

2016-05-12

This paper introduces the sensor-networked IoT model as a prototype to support the design of Body Area Network (BAN) applications for healthcare. Using the model, we analyze the synergistic effect of the functional requirements (data collection from the human body and transferring it to the top level) and non-functional requirements (trade-offs between energy-security-environmental factors, treated as Quality-of-Service (QoS)). We use feature models to represent the requirements at the earliest stage for the analysis and describe a model-driven methodology to design the possible BAN applications. Firstly, we specify the requirements as the problem domain (PD) variability model for the BAN applications. Next, we introduce the generative technology (meta-programming as the solution domain (SD)) and the mapping procedure to map the PD feature-based variability model onto the SD feature model. Finally, we create an executable meta-specification that represents the BAN functionality to describe the variability of the problem domain though transformations. The meta-specification (along with the meta-language processor) is a software generator for multiple BAN-oriented applications. We validate the methodology with experiments and a case study to generate a family of programs for the BAN sensor controllers. This enables to obtain the adequate measure of QoS efficiently through the interactive adjustment of the meta-parameter values and re-generation process for the concrete BAN application.

Model-Driven Approach for Body Area Network Application Development

PubMed Central

Venčkauskas, Algimantas; Štuikys, Vytautas; Jusas, Nerijus; Burbaitė, Renata

2016-01-01

This paper introduces the sensor-networked IoT model as a prototype to support the design of Body Area Network (BAN) applications for healthcare. Using the model, we analyze the synergistic effect of the functional requirements (data collection from the human body and transferring it to the top level) and non-functional requirements (trade-offs between energy-security-environmental factors, treated as Quality-of-Service (QoS)). We use feature models to represent the requirements at the earliest stage for the analysis and describe a model-driven methodology to design the possible BAN applications. Firstly, we specify the requirements as the problem domain (PD) variability model for the BAN applications. Next, we introduce the generative technology (meta-programming as the solution domain (SD)) and the mapping procedure to map the PD feature-based variability model onto the SD feature model. Finally, we create an executable meta-specification that represents the BAN functionality to describe the variability of the problem domain though transformations. The meta-specification (along with the meta-language processor) is a software generator for multiple BAN-oriented applications. We validate the methodology with experiments and a case study to generate a family of programs for the BAN sensor controllers. This enables to obtain the adequate measure of QoS efficiently through the interactive adjustment of the meta-parameter values and re-generation process for the concrete BAN application. PMID:27187394

Effect of spin transfer torque on domain wall motion regimes in [Co/Ni] superlattice wires

NASA Astrophysics Data System (ADS)

Le Gall, S.; Vernier, N.; Montaigne, F.; Thiaville, A.; Sampaio, J.; Ravelosona, D.; Mangin, S.; Andrieu, S.; Hauet, T.

2017-05-01

The combined effect of magnetic field and current on domain wall motion is investigated in epitaxial [Co/Ni] microwires. Both thermally activated and flow regimes are found to be strongly affected by current. All experimental data can be understood by taking into account both adiabatic and nonadiabatic components of the spin transfer torque, the parameters of which are extracted. In the precessional flow regime, it is shown that the domain wall can move in the electron flow direction against a strong applied field, as previously observed. In addition, for a large range of applied magnetic field and injected current, a stochastic domain wall displacement after each pulse is observed. Two-dimensional micromagnetic simulations, including some disorder, show a random fluctuation of the domain wall position that qualitatively matches the experimental results.

Uncertainty of Monetary Valued Ecosystem Services – Value Transfer Functions for Global Mapping

PubMed Central

Schmidt, Stefan; Manceur, Ameur M.; Seppelt, Ralf

2016-01-01

Growing demand of resources increases pressure on ecosystem services (ES) and biodiversity. Monetary valuation of ES is frequently seen as a decision-support tool by providing explicit values for unconsidered, non-market goods and services. Here we present global value transfer functions by using a meta-analytic framework for the synthesis of 194 case studies capturing 839 monetary values of ES. For 12 ES the variance of monetary values could be explained with a subset of 93 study- and site-specific variables by utilizing boosted regression trees. This provides the first global quantification of uncertainties and transferability of monetary valuations. Models explain from 18% (water provision) to 44% (food provision) of variance and provide statistically reliable extrapolations for 70% (water provision) to 91% (food provision) of the terrestrial earth surface. Although the application of different valuation methods is a source of uncertainty, we found evidence that assuming homogeneity of ecosystems is a major error in value transfer function models. Food provision is positively correlated with better life domains and variables indicating positive conditions for human well-being. Water provision and recreation service show that weak ownerships affect valuation of other common goods negatively (e.g. non-privately owned forests). Furthermore, we found support for the shifting baseline hypothesis in valuing climate regulation. Ecological conditions and societal vulnerability determine valuation of extreme event prevention. Valuation of habitat services is negatively correlated with indicators characterizing less favorable areas. Our analysis represents a stepping stone to establish a standardized integration of and reporting on uncertainties for reliable and valid benefit transfer as an important component for decision support. PMID:26938447

Mindfulness and the aging brain: a proposed paradigm shift

PubMed Central

Prakash, Ruchika Shaurya; De Leon, Angeline A.; Patterson, Beth; Schirda, Brittney L.; Janssen, Alisha L.

2014-01-01

There has been a proliferation of cognitive training studies investigating the efficacy of various cognitive training paradigms as well as strategies for improving cognitive control in the elderly. While some have found support for the transfer of training, the majority of training studies show modest to no transfer effects. When transfer effects have been observed, the mechanisms contributing to enhanced functioning have been difficult to dissociate. In this review, we provide a theoretical rationale for the study of mindfulness in older adults as a particular type of training program designed to improve cognitive control by capitalizing on older adults’ acquired behavioral orientation toward higher socioemotional goals. Given the synergistic relationship between emotional and cognitive control processes, the paradoxical divergence in older adults’ functional trajectory in these respective domains, and the harmonious interplay of cognitive and emotional control embedded in the practice of mindfulness, we propose mindfulness training as an opportunistic approach to cultivating cognitive benefits in older adults. The study of mindfulness within aging, we argue, capitalizes on a fundamental finding of the socioemotional aging literature, namely the preferential change in motivational goals of older adults from ones involving future-oriented wants and desires to present-focused emotion regulation and gratification. PMID:25009492

Music training and inhibitory control: a multidimensional model.

PubMed

Moreno, Sylvain; Farzan, Faranak

2015-03-01

Training programs aimed to improve cognitive skills have either yielded mixed results or remain to be validated. The limited benefits of such regimens are largely attributable to weak understanding of (1) how (and which) interventions provide the most cognitive improvements; and (2) how brain networks and neural mechanisms that underlie specific cognitive abilities can be modified selectively. Studies indicate that music training leads to robust and long-lasting benefits to behavior. Importantly, behavioral advantages conferred by music extend beyond perceptual abilities to even nonauditory functions, such as inhibitory control (IC) and its neural correlates. Alternative forms of arts engagement or brain training do not appear to yield such enhancements, which suggests that music uniquely taps into brain networks subserving a variety of auditory as well as domain-general mechanisms such as IC. To account for such widespread benefits of music training, we propose a framework of transfer effects characterized by three dimensions: level of processing, nature of the transfer, and involvement of executive functions. We suggest that transfer of skills is mediated through modulation of general cognitive processes, in particular IC. We believe that this model offers a viable framework to test the extent and limitations of music-related changes. © 2014 New York Academy of Sciences.

Simulation requirements for the Large Deployable Reflector (LDR)

NASA Technical Reports Server (NTRS)

Soosaar, K.

1984-01-01

Simulation tools for the large deployable reflector (LDR) are discussed. These tools are often the transfer function variety equations. However, transfer functions are inadequate to represent time-varying systems for multiple control systems with overlapping bandwidths characterized by multi-input, multi-output features. Frequency domain approaches are the useful design tools, but a full-up simulation is needed. Because of the need for a dedicated computer for high frequency multi degree of freedom components encountered, non-real time smulation is preferred. Large numerical analysis software programs are useful only to receive inputs and provide output to the next block, and should be kept out of the direct loop of simulation. The following blocks make up the simulation. The thermal model block is a classical heat transfer program. It is a non-steady state program. The quasistatic block deals with problems associated with rigid body control of reflector segments. The steady state block assembles data into equations of motion and dynamics. A differential raytrace is obtained to establish a change in wave aberrations. The observation scene is described. The focal plane module converts the photon intensity impinging on it into electron streams or into permanent film records.

Mechanistic insight into the functional transition of the enzyme guanylate kinase induced by a single mutation

PubMed Central

Zhang, Yuebin; Niu, Huiyan; Li, Yan; Chu, Huiying; Shen, Hujun; Zhang, Dinglin; Li, Guohui

2015-01-01

Dramatic functional changes of enzyme usually require scores of alterations in amino acid sequence. However, in the case of guanylate kinase (GK), the functional novelty is induced by a single (S→P) mutation, leading to the functional transition of the enzyme from a phosphoryl transfer kinase into a phosphorprotein interaction domain. Here, by using molecular dynamic (MD) and metadynamics simulations, we provide a comprehensive description of the conformational transitions of the enzyme after mutating serine to proline. Our results suggest that the serine plays a crucial role in maintaining the closed conformation of wild-type GK and the GMP recognition. On the contrary, the S→P mutant exhibits a stable open conformation and loses the ability of ligand binding, which explains its functional transition from the GK enzyme to the GK domain. Furthermore, the free energy profiles (FEPs) obtained by metadymanics clearly demonstrate that the open-closed conformational transition in WT GK is positive correlated with the process of GMP binding, indicating the GMP-induced closing motion of GK enzyme, which is not observed in the mutant. In addition, the FEPs show that the S→P mutation can also leads to the mis-recognition of GMP, explaining the vanishing of catalytic activity of the mutant. PMID:25672880

Mechanistic insight into the functional transition of the enzyme guanylate kinase induced by a single mutation.

PubMed

Zhang, Yuebin; Niu, Huiyan; Li, Yan; Chu, Huiying; Shen, Hujun; Zhang, Dinglin; Li, Guohui

2015-02-12

Dramatic functional changes of enzyme usually require scores of alterations in amino acid sequence. However, in the case of guanylate kinase (GK), the functional novelty is induced by a single (S→P) mutation, leading to the functional transition of the enzyme from a phosphoryl transfer kinase into a phosphorprotein interaction domain. Here, by using molecular dynamic (MD) and metadynamics simulations, we provide a comprehensive description of the conformational transitions of the enzyme after mutating serine to proline. Our results suggest that the serine plays a crucial role in maintaining the closed conformation of wild-type GK and the GMP recognition. On the contrary, the S→P mutant exhibits a stable open conformation and loses the ability of ligand binding, which explains its functional transition from the GK enzyme to the GK domain. Furthermore, the free energy profiles (FEPs) obtained by metadymanics clearly demonstrate that the open-closed conformational transition in WT GK is positive correlated with the process of GMP binding, indicating the GMP-induced closing motion of GK enzyme, which is not observed in the mutant. In addition, the FEPs show that the S→P mutation can also leads to the mis-recognition of GMP, explaining the vanishing of catalytic activity of the mutant.

Enhanced spin transfer torque effect for transverse domain walls in cylindrical nanowires

NASA Astrophysics Data System (ADS)

Franchin, Matteo; Knittel, Andreas; Albert, Maximilian; Chernyshenko, Dmitri S.; Fischbacher, Thomas; Prabhakar, Anil; Fangohr, Hans

2011-09-01

Recent studies have predicted extraordinary properties for transverse domain walls in cylindrical nanowires: zero depinning current, the absence of the Walker breakdown, and applications as domain wall oscillators. In order to reliably control the domain wall motion, it is important to understand how they interact with pinning centers, which may be engineered, for example, through modulations in the nanowire geometry (such as notches or extrusions) or in the magnetic properties of the material. In this paper we study the motion and depinning of transverse domain walls through pinning centers in ferromagnetic cylindrical nanowires. We use (i) magnetic fields and (ii) spin-polarized currents to drive the domain walls along the wire. The pinning centers are modelled as a section of the nanowire which exhibits a uniaxial crystal anisotropy where the anisotropy easy axis and the wire axis enclose a variable angle θP. Using (i) magnetic fields, we find that the minimum and the maximum fields required to push the domain wall through the pinning center differ by 30%. On the contrary, using (ii) spin-polarized currents, we find variations of a factor 130 between the minimum value of the depinning current density (observed for θP=0∘, i.e., anisotropy axis pointing parallel to the wire axis) and the maximum value (for θP=90∘, i.e., anisotropy axis perpendicular to the wire axis). We study the depinning current density as a function of the height of the energy barrier of the pinning center using numerical and analytical methods. We find that for an industry standard energy barrier of 40kBT, a depinning current of about 5μA (corresponding to a current density of 6×1010A/m2 in a nanowire of 10nm diameter) is sufficient to depin the domain wall. We reveal and explain the mechanism that leads to these unusually low depinning currents. One requirement for this depinning mechanism is for the domain wall to be able to rotate around its own axis. With the right barrier design, the spin torque transfer term is acting exactly against the damping in the micromagnetic system, and thus the low current density is sufficient to accumulate enough energy quickly. These key insights may be crucial in furthering the development of novel memory technologies, such as the racetrack memory, that can be controlled through low current densities.

Source Biases in Magnetotelluric Transfer Functions due to Pc3/Pc4 ( 10-100s) Geomagnetic Activity at Mid-Latitudes

NASA Astrophysics Data System (ADS)

Murphy, B. S.; Egbert, G. D.

2017-12-01

Discussion of possible bias in magnetotelluric (MT) transfer functions due to the finite spatial scale of external source fields has largely focused on long periods (>1000 s), where skin depths are large, and high latitudes (>60° N), where sources are dominated by narrow electrojets. However, a significant fraction ( 15%) of the 1000 EarthScope USArray apparent resistivity and phase curves exhibit nonphysical "humps" over a narrow period range (typically between 25-60 s) that are suggestive of narrow-band source effects. Maps of locations in the US where these biases are seen support this conclusion: they mostly occur in places where the Earth is highly resistive, such as cratonic regions, where skin depths are largest and hence where susceptibility to bias from short-wavelength sources would be greatest. We have analyzed EarthScope MT time series using cross-phase techniques developed in the space physics community to measure the period of local field line resonances associated with geomagnetic pulsations (Pc's). In most cases the biases occur near the periods of field line resonance determined from this analysis, suggesting that at mid-latitude ( 30°-50° N) Pc's can bias the time-averaged MT transfer functions. Because Pc's have short meridional wavelengths (hundreds of km), even at these relatively short periods the plane-wave assumption of the MT technique may be violated, at least in resistive domains with large skin depths. It is unclear if these biases (generally small) are problematic for MT data inversion, but their presence in the transfer functions is already a useful zeroth-order indicator of resistive regions of the Earth.

Synthesis of Natural Electric and Magnetic Time Series Using Impulse Responses of Inter-station Transfer Functions and a Reference

NASA Astrophysics Data System (ADS)

Wang, H.; Cheng, J.

2017-12-01

A method to Synthesis natural electric and magnetic Time series is proposed whereby the time series of local site are derived using an Impulse Response and a reference (STIR). The method is based on the assumption that the external source of magnetic fields are uniform, and the electric and magnetic fields acquired at the surface satisfy a time-independent linear relation in frequency domain.According to the convolution theorem, we can synthesize natural electric and magnetic time series using the impulse responses of inter-station transfer functions with a reference. Applying this method, two impulse responses need to be estimated: the quasi-MT impulse response tensor and the horizontal magnetic impulse response tensor. These impulse response tensors relate the local horizontal electric and magnetic components with the horizontal magnetic components at a reference site, respectively. Some clean segments of times series are selected to estimate impulse responses by using least-square (LS) method. STIR is similar with STIN (Wang, 2017), but STIR does not need to estimate the inter-station transfer functions, and the synthesized data are more accurate in high frequency, where STIN fails when the inter-station transfer functions are contaminated severely. A test with good quality of MT data shows that synthetic time-series are similar to natural electric and magnetic time series. For contaminated AMT example, when this method is used to remove noise present at the local site, the scatter of MT sounding curves are clear reduced, and the data quality are improved. *This work is funded by National Key R&D Program of China(2017YFC0804105),National Natural Science Foundation of China (41604064, 51574250), State Key Laboratory of Coal Resources and Safe Mining ,China University of Mining & Technology,(SKLCRSM16DC09)

Finite state modeling of aeroelastic systems

NASA Technical Reports Server (NTRS)

Vepa, R.

1977-01-01

A general theory of finite state modeling of aerodynamic loads on thin airfoils and lifting surfaces performing completely arbitrary, small, time-dependent motions in an airstream is developed and presented. The nature of the behavior of the unsteady airloads in the frequency domain is explained, using as raw materials any of the unsteady linearized theories that have been mechanized for simple harmonic oscillations. Each desired aerodynamic transfer function is approximated by means of an appropriate Pade approximant, that is, a rational function of finite degree polynomials in the Laplace transform variable. The modeling technique is applied to several two dimensional and three dimensional airfoils. Circular, elliptic, rectangular and tapered planforms are considered as examples. Identical functions are also obtained for control surfaces for two and three dimensional airfoils.

Activity of a C-terminal plant homeodomain (PHD) of Msc1 is essential for function.

PubMed

Qiu, Xinxing; Dul, Barbara E; Walworth, Nancy C

2010-11-19

Msc1, a member of the Jarid1 family of putative histone demethylases, is required for chromosome stability in fission yeast. Msc1 associates with the Swr1 complex that facilitates deposition of histone H2A.Z into chromatin. To assess the function of Msc1 in the Swr1 complex, domains of Msc1 necessary for interaction with Swr1 were identified. The C-terminal plant homeodomain (PHD) 2 and PHD3 of Msc1 are sufficient to confer association with Swr1 and allow Msc1 to function in the context of kinetochore mutants. On the other hand, a mutant with a single amino acid substitution in PHD2 within the full-length Msc1 protein retains the ability to bind to Swr1 but eliminates the function of Msc1 in combination with kinetochore mutants. Thus, Swr1 association is critical but not sufficient for Msc1 function. An activity of Msc1 that depends on the cysteine residue within PHD2 of Msc1 is likewise critical for function. On the basis of our observation that the PHDs of Msc1 act as E3 ubiquitin ligases and that mutations of cysteine residues within those domains abolish ligase activity, we speculate that the ability of Msc1 to facilitate ubiquitin transfer is critical for the function it mediates through its association with Swr1.

Activity of a C-terminal Plant Homeodomain (PHD) of Msc1 Is Essential for Function*

PubMed Central

Qiu, Xinxing; Dul, Barbara E.; Walworth, Nancy C.

2010-01-01

Msc1, a member of the Jarid1 family of putative histone demethylases, is required for chromosome stability in fission yeast. Msc1 associates with the Swr1 complex that facilitates deposition of histone H2A.Z into chromatin. To assess the function of Msc1 in the Swr1 complex, domains of Msc1 necessary for interaction with Swr1 were identified. The C-terminal plant homeodomain (PHD) 2 and PHD3 of Msc1 are sufficient to confer association with Swr1 and allow Msc1 to function in the context of kinetochore mutants. On the other hand, a mutant with a single amino acid substitution in PHD2 within the full-length Msc1 protein retains the ability to bind to Swr1 but eliminates the function of Msc1 in combination with kinetochore mutants. Thus, Swr1 association is critical but not sufficient for Msc1 function. An activity of Msc1 that depends on the cysteine residue within PHD2 of Msc1 is likewise critical for function. On the basis of our observation that the PHDs of Msc1 act as E3 ubiquitin ligases and that mutations of cysteine residues within those domains abolish ligase activity, we speculate that the ability of Msc1 to facilitate ubiquitin transfer is critical for the function it mediates through its association with Swr1. PMID:20858896

Domain wall structure and interactions in 50 nm wide Cobalt nanowires

NASA Astrophysics Data System (ADS)

Tu, Kun-Hua; Ojha, Shuchi; Ross, Caroline A.

2018-05-01

Arrays of cobalt nanowires with widths of 50 nm, thickness of 5 and 20 nm and periodicity of 70 nm were fabricated by pattern transfer from a self-assembled block copolymer film. Transverse domain walls (DWs) were imaged by magnetic force microscopy, indicating repulsive interactions between DWs of the same sign in the 20 nm thick wires. Micromagnetic simulations were used to identify the interactions in the six distinct cases of a pair of transverse DWs in adjacent wires, considering all the possible combinations of head-to-head and tail-to-tail DWs and the orientation of the core magnetization. The boundary between repulsive and attractive DW interactions is mapped out for wires as a function of thickness, width and interwire spacing.

Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages

PubMed Central

del Sol, Antonio; Araúzo-Bravo, Marcos J; Amoros, Dolors; Nussinov, Ruth

2007-01-01

Background Allosteric communications are vital for cellular signaling. Here we explore a relationship between protein architectural organization and shortcuts in signaling pathways. Results We show that protein domains consist of modules interconnected by residues that mediate signaling through the shortest pathways. These mediating residues tend to be located at the inter-modular boundaries, which are more rigid and display a larger number of long-range interactions than intra-modular regions. The inter-modular boundaries contain most of the residues centrally conserved in the protein fold, which may be crucial for information transfer between amino acids. Our approach to modular decomposition relies on a representation of protein structures as residue-interacting networks, and removal of the most central residue contacts, which are assumed to be crucial for allosteric communications. The modular decomposition of 100 multi-domain protein structures indicates that modules constitute the building blocks of domains. The analysis of 13 allosteric proteins revealed that modules characterize experimentally identified functional regions. Based on the study of an additional functionally annotated dataset of 115 proteins, we propose that high-modularity modules include functional sites and are the basic functional units. We provide examples (the Gαs subunit and P450 cytochromes) to illustrate that the modular architecture of active sites is linked to their functional specialization. Conclusion Our method decomposes protein structures into modules, allowing the study of signal transmission between functional sites. A modular configuration might be advantageous: it allows signaling proteins to expand their regulatory linkages and may elicit a broader range of control mechanisms either via modular combinations or through modulation of inter-modular linkages. PMID:17531094

Small scale homelike special care units and traditional special care units: effects on cognition in dementia; a longitudinal controlled intervention study.

PubMed

Kok, Jeroen S; van Heuvelen, Marieke J G; Berg, Ina J; Scherder, Erik J A

2016-02-16

Evidence shows that living in small scale homelike Special Care Units (SCU) has positive effects on behavioural and psychological symptoms of patients with dementia. Effects on cognitive functioning in relation to care facilities, however, are scarcely investigated. The purpose of this study is to gain more insight into the effects of living in small scale homelike Special Care Units, compared to regular SCU's, on the course of cognitive functioning in dementia. A group of 67 patients with dementia who moved from a regular SCU to a small scale homelike SCU and a group of 48 patients with dementia who stayed in a regular SCU participated in the study. Cognitive and behavioural functioning was assessed by means of a neuropsychological test battery and observation scales one month before (baseline), as well as 3 (post) and 6 months (follow-up) after relocation. Comparing the post and follow-up measurement with the baseline measurement, no significant differences on separate measures of cognitive functioning between both groups were found. Additional analyses, however, on 'domain clusters' revealed that global cognitive functioning of the small scale homelike SCU group showed significantly less cognitive decline three months after the transfer (p < 0.05). Effect sizes (95% CI) show a tendency for better aspects of cognition in favour of the homelike small scaled SCU group, i.e., visual memory, picture recognition, cognitive decline as observed by representatives and the clustered domains episodic memory and global cognitive functioning. While there is no significant longitudinal effect on the progression of cognitive decline comparing small scaled homelike SCU's with regular SCU's for patients with dementia, analyses on the domain clusters and effect sizes cautiously suggest differences in favour of the small scaled homelike SCU for different aspects of cognition.

Modified superposition: A simple time series approach to closed-loop manual controller identification

NASA Technical Reports Server (NTRS)

Biezad, D. J.; Schmidt, D. K.; Leban, F.; Mashiko, S.

1986-01-01

Single-channel pilot manual control output in closed-tracking tasks is modeled in terms of linear discrete transfer functions which are parsimonious and guaranteed stable. The transfer functions are found by applying a modified super-position time series generation technique. A Levinson-Durbin algorithm is used to determine the filter which prewhitens the input and a projective (least squares) fit of pulse response estimates is used to guarantee identified model stability. Results from two case studies are compared to previous findings, where the source of data are relatively short data records, approximately 25 seconds long. Time delay effects and pilot seasonalities are discussed and analyzed. It is concluded that single-channel time series controller modeling is feasible on short records, and that it is important for the analyst to determine a criterion for best time domain fit which allows association of model parameter values, such as pure time delay, with actual physical and physiological constraints. The purpose of the modeling is thus paramount.

Architecture of the nitric-oxide synthase holoenzyme reveals large conformational changes and a calmodulin-driven release of the FMN domain.

PubMed

Yokom, Adam L; Morishima, Yoshihiro; Lau, Miranda; Su, Min; Glukhova, Alisa; Osawa, Yoichi; Southworth, Daniel R

2014-06-13

Nitric-oxide synthase (NOS) is required in mammals to generate NO for regulating blood pressure, synaptic response, and immune defense. NOS is a large homodimer with well characterized reductase and oxygenase domains that coordinate a multistep, interdomain electron transfer mechanism to oxidize l-arginine and generate NO. Ca(2+)-calmodulin (CaM) binds between the reductase and oxygenase domains to activate NO synthesis. Although NOS has long been proposed to adopt distinct conformations that alternate between interflavin and FMN-heme electron transfer steps, structures of the holoenzyme have remained elusive and the CaM-bound arrangement is unknown. Here we have applied single particle electron microscopy (EM) methods to characterize the full-length of the neuronal isoform (nNOS) complex and determine the structural mechanism of CaM activation. We have identified that nNOS adopts an ensemble of open and closed conformational states and that CaM binding induces a dramatic rearrangement of the reductase domain. Our three-dimensional reconstruction of the intact nNOS-CaM complex reveals a closed conformation and a cross-monomer arrangement with the FMN domain rotated away from the NADPH-FAD center, toward the oxygenase dimer. This work captures, for the first time, the reductase-oxygenase structural arrangement and the CaM-dependent release of the FMN domain that coordinates to drive electron transfer across the domains during catalysis. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Study of lifting operation of a tripod foundation for offshore wind turbine

NASA Astrophysics Data System (ADS)

Zhu, H.; Li, L.; Ong, M. C.

2017-12-01

This study addresses numerical analysis of the installation of a tripod foundation using a heavy lift vessel (HLV). Limiting sea states are firstly predicted in the frequency domain based on crane tip vertical motions using linear transfer functions. Then, numerical modelling and simulations are carried out in the time domain to analyse the coupled dynamic system taking into consideration of the nonlinearities of the system. In time-domain analysis, two lifting phases are brought into focus, i.e., the lift-off and the lowering phases. For the lift-off phase, two scenarios are considered, i.e., lift-off from the own deck of the HLV and lift-off from a transport barge. Moreover, comparative studies using two types of installation vessels, a floating vessel and a Jack-up, are investigated for the lowering process. Critical responses including the motions of the tripod and the lift wire tensions are presented and compared under various environmental and loading conditions.

Does inhibitory control training transfer?: behavioral and neural effects on an untrained emotion regulation task.

PubMed

Beauchamp, Kathryn G; Kahn, Lauren E; Berkman, Elliot T

2016-09-01

Inhibitory control (IC) is a critical neurocognitive skill for successfully navigating challenges across domains. Several studies have attempted to use training to improve neurocognitive skills such as IC, but few have found that training generalizes to performance on non-trained tasks. We used functional magnetic resonance imaging (fMRI) to investigate the effect of IC training on a related but untrained emotion regulation (ER) task with the goal of clarifying how training alters brain function and why its effects typically do not transfer across tasks. We suggest hypotheses for training-related changes in activation relevant to transfer effects: the strength model and several plausible alternatives (shifting priorities, stimulus-response automaticity, scaffolding). Sixty participants completed three weeks of IC training and underwent fMRI scanning before and after. The training produced pre- to post-training changes in neural activation during the ER task in the absence of behavioral changes. Specifically, individuals in the training group demonstrated reduced activation during ER in the left inferior frontal gyrus and supramarginal gyrus, key regions in the IC neural network. This result is less consistent with the strength model and more consistent with a motivational account. Implications for future work aiming to further pinpoint mechanisms of training transfer are discussed. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Planck 2013 results. VII. HFI time response and beams

NASA Astrophysics Data System (ADS)

Planck Collaboration; Ade, P. A. R.; Aghanim, N.; Armitage-Caplan, C.; Arnaud, M.; Ashdown, M.; Atrio-Barandela, F.; Aumont, J.; Baccigalupi, C.; Banday, A. J.; Barreiro, R. B.; Battaner, E.; Benabed, K.; Benoît, A.; Benoit-Lévy, A.; Bernard, J.-P.; Bersanelli, M.; Bielewicz, P.; Bobin, J.; Bock, J. J.; Bond, J. R.; Borrill, J.; Bouchet, F. R.; Bowyer, J. W.; Bridges, M.; Bucher, M.; Burigana, C.; Cardoso, J.-F.; Catalano, A.; Challinor, A.; Chamballu, A.; Chary, R.-R.; Chiang, H. C.; Chiang, L.-Y.; Christensen, P. R.; Church, S.; Clements, D. L.; Colombi, S.; Colombo, L. P. L.; Couchot, F.; Coulais, A.; Crill, B. P.; Curto, A.; Cuttaia, F.; Danese, L.; Davies, R. D.; de Bernardis, P.; de Rosa, A.; de Zotti, G.; Delabrouille, J.; Delouis, J.-M.; Désert, F.-X.; Diego, J. M.; Dole, H.; Donzelli, S.; Doré, O.; Douspis, M.; Dunkley, J.; Dupac, X.; Efstathiou, G.; Enßlin, T. A.; Eriksen, H. K.; Finelli, F.; Forni, O.; Frailis, M.; Fraisse, A. A.; Franceschi, E.; Galeotta, S.; Ganga, K.; Giard, M.; Giraud-Héraud, Y.; González-Nuevo, J.; Górski, K. M.; Gratton, S.; Gregorio, A.; Gruppuso, A.; Gudmundsson, J. E.; Haissinski, J.; Hansen, F. K.; Hanson, D.; Harrison, D.; Henrot-Versillé, S.; Hernández-Monteagudo, C.; Herranz, D.; Hildebrandt, S. R.; Hivon, E.; Hobson, M.; Holmes, W. A.; Hornstrup, A.; Hou, Z.; Hovest, W.; Huffenberger, K. M.; Jaffe, A. H.; Jaffe, T. R.; Jones, W. C.; Juvela, M.; Keihänen, E.; Keskitalo, R.; Kisner, T. S.; Kneissl, R.; Knoche, J.; Knox, L.; Kunz, M.; Kurki-Suonio, H.; Lagache, G.; Lamarre, J.-M.; Lasenby, A.; Laureijs, R. J.; Lawrence, C. R.; Leonardi, R.; Leroy, C.; Lesgourgues, J.; Liguori, M.; Lilje, P. B.; Linden-Vørnle, M.; López-Caniego, M.; Lubin, P. M.; Macías-Pérez, J. F.; MacTavish, C. J.; Maffei, B.; Mandolesi, N.; Maris, M.; Marshall, D. J.; Martin, P. G.; Martínez-González, E.; Masi, S.; Massardi, M.; Matarrese, S.; Matsumura, T.; Matthai, F.; Mazzotta, P.; McGehee, P.; Melchiorri, A.; Mendes, L.; Mennella, A.; Migliaccio, M.; Mitra, S.; Miville-Deschênes, M.-A.; Moneti, A.; Montier, L.; Morgante, G.; Mortlock, D.; Munshi, D.; Murphy, J. A.; Naselsky, P.; Nati, F.; Natoli, P.; Netterfield, C. B.; Nørgaard-Nielsen, H. U.; Noviello, F.; Novikov, D.; Novikov, I.; Osborne, S.; Oxborrow, C. A.; Paci, F.; Pagano, L.; Pajot, F.; Paoletti, D.; Pasian, F.; Patanchon, G.; Perdereau, O.; Perotto, L.; Perrotta, F.; Piacentini, F.; Piat, M.; Pierpaoli, E.; Pietrobon, D.; Plaszczynski, S.; Pointecouteau, E.; Polegre, A. M.; Polenta, G.; Ponthieu, N.; Popa, L.; Poutanen, T.; Pratt, G. W.; Prézeau, G.; Prunet, S.; Puget, J.-L.; Rachen, J. P.; Reinecke, M.; Remazeilles, M.; Renault, C.; Ricciardi, S.; Riller, T.; Ristorcelli, I.; Rocha, G.; Rosset, C.; Roudier, G.; Rowan-Robinson, M.; Rusholme, B.; Sandri, M.; Santos, D.; Sauvé, A.; Savini, G.; Scott, D.; Shellard, E. P. S.; Spencer, L. D.; Starck, J.-L.; Stolyarov, V.; Stompor, R.; Sudiwala, R.; Sureau, F.; Sutton, D.; Suur-Uski, A.-S.; Sygnet, J.-F.; Tauber, J. A.; Tavagnacco, D.; Terenzi, L.; Tomasi, M.; Tristram, M.; Tucci, M.; Umana, G.; Valenziano, L.; Valiviita, J.; Van Tent, B.; Vielva, P.; Villa, F.; Vittorio, N.; Wade, L. A.; Wandelt, B. D.; Yvon, D.; Zacchei, A.; Zonca, A.

2014-11-01

This paper characterizes the effective beams, the effective beam window functions and the associated errors for the Planck High Frequency Instrument (HFI) detectors. The effective beam is theangular response including the effect of the optics, detectors, data processing and the scan strategy. The window function is the representation of this beam in the harmonic domain which is required to recover an unbiased measurement of the cosmic microwave background angular power spectrum. The HFI is a scanning instrument and its effective beams are the convolution of: a) the optical response of the telescope and feeds; b) the processing of the time-ordered data and deconvolution of the bolometric and electronic transfer function; and c) the merging of several surveys to produce maps. The time response transfer functions are measured using observations of Jupiter and Saturn and by minimizing survey difference residuals. The scanning beam is the post-deconvolution angular response of the instrument, and is characterized with observations of Mars. The main beam solid angles are determined to better than 0.5% at each HFI frequency band. Observations of Jupiter and Saturn limit near sidelobes (within 5°) to about 0.1% of the total solid angle. Time response residuals remain as long tails in the scanning beams, but contribute less than 0.1% of the total solid angle. The bias and uncertainty in the beam products are estimated using ensembles of simulated planet observations that include the impact of instrumental noise and known systematic effects. The correlation structure of these ensembles is well-described by five error eigenmodes that are sub-dominant to sample variance and instrumental noise in the harmonic domain. A suite of consistency tests provide confidence that the error model represents a sufficient description of the data. The total error in the effective beam window functions is below 1% at 100 GHz up to multipole ℓ ~ 1500, and below 0.5% at 143 and 217 GHz up to ℓ ~ 2000.

Renal blood flow dynamics in inbred rat strains provides insight into autoregulation.

PubMed

A Mitrou, Nicholas G; Cupples, William A

2014-01-01

Renal autoregulation maintains stable renal blood flow in the face of constantly fluctuating blood pressure. Autoregulation is also the only mechanism that protects the delicate glomerular capillaries when blood pressure increases. In order to understand autoregulation, the renal blood flow response to changing blood pressure is studied. The steadystate response of blood flow is informative, but limits investigation of the individual mechanisms of autoregulation. The dynamics of autoregulation can be probed with transfer function analysis. The frequency-domain analysis of autoregulation allows investigators to probe the relative activity of each mechanism of autoregulation. We discuss the methodology and interpretation of transfer function analysis. Autoregulation is routinely studied in the rat, of which there are many inbred strains. There are multiple strains of rat that are either selected or inbred as models of human pathology. We discuss relevant characteristics of Brown Norway, Spontaneously hypertensive, Dahl, and Fawn-Hooded hypertensive rats and explore differences among these strains in blood pressure, dynamic autoregulation, and susceptibility to hypertensive renal injury. Finally we show that the use of transfer function analysis in these rat strains has contributed to our understanding of the physiology and pathophysiology of autoregulation and hypertensive renal disease.Interestingly all these strains demonstrate effective tubuloglomerular feedback suggesting that this mechanism is not sufficient for effective autoregulation. In contrast, obligatory or conditional failure of the myogenic mechanism suggests that this component is both necessary and sufficient for autoregulation.

Intensification of heat transfer across falling liquid films

NASA Astrophysics Data System (ADS)

Ruyer-Quil, Christian; Cellier, Nicolas; Stutz, Benoit; Caney, Nadia; Bandelier, Philippe; Locie Team; Legi Team

2017-11-01

The wavy motion of a liquid film is well known to intensify heat or mass transfers. Yet, if film thinning and wave merging are generally invoked, the physical mechanisms which enable this intensification are still unclear. We propose a systematic investigation of the impact of wavy motions on the heat transfer across 2D falling films on hot plates as a function of the inlet frequency and flow parameters. Computations over extended domains and for sufficient durations to achieve statistically established flows have been made possible by low-dimensional modeling and the development of a fast temporal solver based on graph optimizations. Heat transfer has been modeled using the weighted residual technique as a set of two evolution equations for the free-surface temperature and the wall heat flux. This new model solves the shortcomings of previous attempts, namely their inability to capture the onset of thermal boundary layers in large-amplitude waves and their limitation to low Prandtl numbers. Our study reveals that heat transfer is enhanced at the crests of the waves and that heat transfer intensification is maximum at the maximum of density of wave crests, which does not correspond to the natural wavy regime (no inlet forcing). Supports from Institut Universitaire de France and Région Auvergne-Rhones-Alpes are warmly acknowledged.

The Case for Case-Based Transfer Learning

DTIC Science & Technology

2011-01-01

Thorndike and Woodworth 1901; Perkins and Salomon 1994; Bransford, Brown, and Cocking 2000), among other disciplines. Transfer learning uses knowledge...Transfer Learning for Rein- forcement Learning Domains: A Survey. Journal of Machine Learning Research 10(1): 1633–1685. Thorndike , E. L., and

Domain activities of PapC usher reveal the mechanism of action of an Escherichia coli molecular machine.

PubMed

Volkan, Ender; Ford, Bradley A; Pinkner, Jerome S; Dodson, Karen W; Henderson, Nadine S; Thanassi, David G; Waksman, Gabriel; Hultgren, Scott J

2012-06-12

P pili are prototypical chaperone-usher pathway-assembled pili used by Gram-negative bacteria to adhere to host tissues. The PapC usher contains five functional domains: a transmembrane β-barrel, a β-sandwich Plug, an N-terminal (periplasmic) domain (NTD), and two C-terminal (periplasmic) domains, CTD1 and CTD2. Here, we delineated usher domain interactions between themselves and with chaperone-subunit complexes and showed that overexpression of individual usher domains inhibits pilus assembly. Prior work revealed that the Plug domain occludes the pore of the transmembrane domain of a solitary usher, but the chaperone-adhesin-bound usher has its Plug displaced from the pore, adjacent to the NTD. We demonstrate an interaction between the NTD and Plug domains that suggests a biophysical basis for usher gating. Furthermore, we found that the NTD exhibits high-affinity binding to the chaperone-adhesin (PapDG) complex and low-affinity binding to the major tip subunit PapE (PapDE). We also demonstrate that CTD2 binds with lower affinity to all tested chaperone-subunit complexes except for the chaperone-terminator subunit (PapDH) and has a catalytic role in dissociating the NTD-PapDG complex, suggesting an interplay between recruitment to the NTD and transfer to CTD2 during pilus initiation. The Plug domain and the NTD-Plug complex bound all of the chaperone-subunit complexes tested including PapDH, suggesting that the Plug actively recruits chaperone-subunit complexes to the usher and is the sole recruiter of PapDH. Overall, our studies reveal the cooperative, active roles played by periplasmic domains of the usher to initiate, grow, and terminate a prototypical chaperone-usher pathway pilus.

Functional analysis of aldehyde oxidase using expressed chimeric enzyme between monkey and rat.

PubMed

Itoh, Kunio; Asakawa, Tasuku; Hoshino, Kouichi; Adachi, Mayuko; Fukiya, Kensuke; Watanabe, Nobuaki; Tanaka, Yorihisa

2009-01-01

Aldehyde oxidase (AO) is a homodimer with a subunit molecular mass of approximately 150 kDa. Each subunit consists of about 20 kDa 2Fe-2S cluster domain storing reducing equivalents, about 40 kDa flavine adenine dinucleotide (FAD) domain and about 85 kDa molybdenum cofactor (MoCo) domain containing a substrate binding site. In order to clarify the properties of each domain, especially substrate binding domain, chimeric cDNAs were constructed by mutual exchange of 2Fe-2S/FAD and MoCo domains between monkey and rat. Chimeric monkey/rat AO was referred to one with monkey type 2Fe-2S/FAD domains and a rat type MoCo domain. Rat/monkey AO was vice versa. AO-catalyzed 2-oxidation activities of (S)-RS-8359 were measured using the expressed enzyme in Escherichia coli. Substrate inhibition was seen in rat AO and chimeric monkey/rat AO, but not in monkey AO and chimeric rat/monkey AO, suggesting that the phenomenon might be dependent on the natures of MoCo domain of rat. A biphasic Eadie-Hofstee profile was observed in monkey AO and chimeric rat/monkey AO, but not rat AO and chimeric monkey/rat AO, indicating that the biphasic profile might be related to the properties of MoCo domain of monkey. Two-fold greater V(max) values were observed in monkey AO than in chimeric rat/monkey AO, and in chimeric monkey/rat AO than in rat AO, suggesting that monkey has the more effective electron transfer system than rat. Thus, the use of chimeric enzymes revealed that 2Fe-2S/FAD and MoCo domains affect the velocity and the quantitative profiles of AO-catalyzed (S)-RS-8359 2-oxidation, respectively.

An Efficient Implementation For Real Time Applications Of The Wigner-Ville Distribution

NASA Astrophysics Data System (ADS)

Boashash, Boualem; Black, Peter; Whitehouse, Harper J.

1986-03-01

The Wigner-Ville Distribution (WVD) is a valuable tool for time-frequency signal analysis. In order to implement the WVD in real time an efficient algorithm and architecture have been developed which may be implemented with commercial components. This algorithm successively computes the analytic signal corresponding to the input signal, forms a weighted kernel function and analyses the kernel via a Discrete Fourier Transform (DFT). To evaluate the analytic signal required by the algorithm it is shown that the time domain definition implemented as a finite impulse response (FIR) filter is practical and more efficient than the frequency domain definition of the analytic signal. The windowed resolution of the WVD in the frequency domain is shown to be similar to the resolution of a windowed Fourier Transform. A real time signal processsor has been designed for evaluation of the WVD analysis system. The system is easily paralleled and can be configured to meet a variety of frequency and time resolutions. The arithmetic unit is based on a pair of high speed VLSI floating-point multiplier and adder chips. Dual operand buses and an independent result bus maximize data transfer rates. The system is horizontally microprogrammed and utilizes a full instruction pipeline. Each microinstruction specifies two operand addresses, a result location, the type of arithmetic and the memory configuration. input and output is via shared memory blocks with front-end processors to handle data transfers during the non access periods of the analyzer.

A mobile-mobile transport model for simulating reactive transport in connected heterogeneous fields

NASA Astrophysics Data System (ADS)

Lu, Chunhui; Wang, Zhiyuan; Zhao, Yue; Rathore, Saubhagya Singh; Huo, Jinge; Tang, Yuening; Liu, Ming; Gong, Rulan; Cirpka, Olaf A.; Luo, Jian

2018-05-01

Mobile-immobile transport models can be effective in reproducing heavily tailed breakthrough curves of concentration. However, such models may not adequately describe transport along multiple flow paths with intermediate velocity contrasts in connected fields. We propose using the mobile-mobile model for simulating subsurface flow and associated mixing-controlled reactive transport in connected fields. This model includes two local concentrations, one in the fast- and the other in the slow-flow domain, which predict both the concentration mean and variance. The normalized total concentration variance within the flux is found to be a non-monotonic function of the discharge ratio with a maximum concentration variance at intermediate values of the discharge ratio. We test the mobile-mobile model for mixing-controlled reactive transport with an instantaneous, irreversible bimolecular reaction in structured and connected random heterogeneous domains, and compare the performance of the mobile-mobile to the mobile-immobile model. The results indicate that the mobile-mobile model generally predicts the concentration breakthrough curves (BTCs) of the reactive compound better. Particularly, for cases of an elliptical inclusion with intermediate hydraulic-conductivity contrasts, where the travel-time distribution shows bimodal behavior, the prediction of both the BTCs and maximum product concentration is significantly improved. Our results exemplify that the conceptual model of two mobile domains with diffusive mass transfer in between is in general good for predicting mixing-controlled reactive transport, and particularly so in cases where the transfer in the low-conductivity zones is by slow advection rather than diffusion.

Hydrolysis at One of the Two Nucleotide-binding Sites Drives the Dissociation of ATP-binding Cassette Nucleotide-binding Domain Dimers

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

Zoghbi, M. E.; Altenberg, G. A.

The functional unit of ATP-binding cassette (ABC) transporters consists of two transmembrane domains and two nucleotide-binding domains (NBDs). ATP binding elicits association of the two NBDs, forming a dimer in a head-to-tail arrangement, with two nucleotides “sandwiched” at the dimer interface. Each of the two nucleotide-binding sites is formed by residues from the two NBDs. We recently found that the prototypical NBD MJ0796 from Methanocaldococcus jannaschii dimerizes in response to ATP binding and dissociates completely following ATP hydrolysis. However, it is still unknown whether dissociation of NBD dimers follows ATP hydrolysis at one or both nucleotide-binding sites. Here, we usedmore » luminescence resonance energy transfer to study heterodimers formed by one active (donor-labeled) and one catalytically defective (acceptor-labeled) NBD. Rapid mixing experiments in a stop-flow chamber showed that NBD heterodimers with one functional and one inactive site dissociated at a rate indistinguishable from that of dimers with two hydrolysis-competent sites. Comparison of the rates of NBD dimer dissociation and ATP hydrolysis indicated that dissociation followed hydrolysis of one ATP. We conclude that ATP hydrolysis at one nucleotide-binding site drives NBD dimer dissociation.« less

Properties and structure of a low-potential, penta-heme cytochrome c 552 from a thermophilic purple sulfur photosynthetic bacterium Thermochromatium tepidum.

PubMed

Chen, Jing-Hua; Yu, Long-Jiang; Boussac, Alain; Wang-Otomo, Zheng-Yu; Kuang, Tingyun; Shen, Jian-Ren

2018-04-24

The thermophilic purple sulfur bacterium Thermochromatium tepidum possesses four main water-soluble redox proteins involved in the electron transfer behavior. Crystal structures have been reported for three of them: a high potential iron-sulfur protein, cytochrome c', and one of two low-potential cytochrome c 552 (which is a flavocytochrome c) have been determined. In this study, we purified another low-potential cytochrome c 552 (LPC), determined its N-terminal amino acid sequence and the whole gene sequence, characterized it with absorption and electron paramagnetic spectroscopy, and solved its high-resolution crystal structure. This novel cytochrome was found to contain five c-type hemes. The overall fold of LPC consists of two distinct domains, one is the five heme-containing domain and the other one is an Ig-like domain. This provides a representative example for the structures of multiheme cytochromes containing an odd number of hemes, although the structures of multiheme cytochromes with an even number of hemes are frequently seen in the PDB database. Comparison of the sequence and structure of LPC with other proteins in the databases revealed several characteristic features which may be important for its functioning. Based on the results obtained, we discuss the possible intracellular function of this LPC in Tch. tepidum.

Implications of Domain-General "Psychological Support Skills" for Transfer of Skill and Acquisition of Expertise

ERIC Educational Resources Information Center

Eccles, David W.; Feltovich, Paul J.

2008-01-01

The article proposes that individuals who acquire certain psychological support skills may experience accelerated learning and enhanced performance in many domains. In support of this proposal, we present evidence that these skills enhance learning and performance, that they are domain-general in that they can be applied in a variety of domains,…

The Hinge Segment of Human NADPH-Cytochrome P450 Reductase in Conformational Switching: The Critical Role of Ionic Strength

PubMed Central

Campelo, Diana; Lautier, Thomas; Urban, Philippe; Esteves, Francisco; Bozonnet, Sophie; Truan, Gilles; Kranendonk, Michel

2017-01-01

NADPH-cytochrome P450 reductase (CPR) is a redox partner of microsomal cytochromes P450 and is a prototype of the diflavin reductase family. CPR contains 3 distinct functional domains: a FMN-binding domain (acceptor reduction), a linker (hinge), and a connecting/FAD domain (NADPH oxidation). It has been demonstrated that the mechanism of CPR exhibits an important step in which it switches from a compact, closed conformation (locked state) to an ensemble of open conformations (unlocked state), the latter enabling electron transfer to redox partners. The conformational equilibrium between the locked and unlocked states has been shown to be highly dependent on ionic strength, reinforcing the hypothesis of the presence of critical salt interactions at the interface between the FMN and connecting FAD domains. Here we show that specific residues of the hinge segment are important in the control of the conformational equilibrium of CPR. We constructed six single mutants and two double mutants of the human CPR, targeting residues G240, S243, I245 and R246 of the hinge segment, with the aim of modifying the flexibility or the potential ionic interactions of the hinge segment. We measured the reduction of cytochrome c at various salt concentrations of these 8 mutants, either in the soluble or membrane-bound form of human CPR. All mutants were found capable of reducing cytochrome c yet with different efficiency and their maximal rates of cytochrome c reduction were shifted to lower salt concentration. In particular, residue R246 seems to play a key role in a salt bridge network present at the interface of the hinge and the connecting domain. Interestingly, the effects of mutations, although similar, demonstrated specific differences when present in the soluble or membrane-bound context. Our results demonstrate that the electrostatic and flexibility properties of the hinge segment are critical for electron transfer from CPR to its redox partners. PMID:29163152

Lipid-regulated sterol transfer between closely apposed membranes by oxysterol-binding protein homologues.

PubMed

Schulz, Timothy A; Choi, Mal-Gi; Raychaudhuri, Sumana; Mears, Jason A; Ghirlando, Rodolfo; Hinshaw, Jenny E; Prinz, William A

2009-12-14

Sterols are transferred between cellular membranes by vesicular and poorly understood nonvesicular pathways. Oxysterol-binding protein-related proteins (ORPs) have been implicated in sterol sensing and nonvesicular transport. In this study, we show that yeast ORPs use a novel mechanism that allows regulated sterol transfer between closely apposed membranes, such as organelle contact sites. We find that the core lipid-binding domain found in all ORPs can simultaneously bind two membranes. Using Osh4p/Kes1p as a representative ORP, we show that ORPs have at least two membrane-binding surfaces; one near the mouth of the sterol-binding pocket and a distal site that can bind a second membrane. The distal site is required for the protein to function in cells and, remarkably, regulates the rate at which Osh4p extracts and delivers sterols in a phosphoinositide-dependent manner. Together, these findings suggest a new model of how ORPs could sense and regulate the lipid composition of adjacent membranes.

Pirating conserved phage mechanisms promotes promiscuous staphylococcal pathogenicity island transfer.

PubMed

Bowring, Janine; Neamah, Maan M; Donderis, Jorge; Mir-Sanchis, Ignacio; Alite, Christian; Ciges-Tomas, J Rafael; Maiques, Elisa; Medmedov, Iltyar; Marina, Alberto; Penadés, José R

2017-08-08

Targeting conserved and essential processes is a successful strategy to combat enemies. Remarkably, the clinically important Staphylococcus aureus pathogenicity islands (SaPIs) use this tactic to spread in nature. SaPIs reside passively in the host chromosome, under the control of the SaPI-encoded master repressor, Stl. It has been assumed that SaPI de-repression is effected by specific phage proteins that bind to Stl, initiating the SaPI cycle. Different SaPIs encode different Stl repressors, so each targets a specific phage protein for its de-repression. Broadening this narrow vision, we report here that SaPIs ensure their promiscuous transfer by targeting conserved phage mechanisms. This is accomplished because the SaPI Stl repressors have acquired different domains to interact with unrelated proteins, encoded by different phages, but in all cases performing the same conserved function. This elegant strategy allows intra- and inter-generic SaPI transfer, highlighting these elements as one of nature's most fascinating subcellular parasites.

Structural and mechanistic insights into phospholipid transfer by Ups1-Mdm35 in mitochondria

NASA Astrophysics Data System (ADS)

Watanabe, Yasunori; Tamura, Yasushi; Kawano, Shin; Endo, Toshiya

2015-08-01

Eukaryotic cells are compartmentalized into membrane-bounded organelles whose functions rely on lipid trafficking to achieve membrane-specific compositions of lipids. Here we focused on the Ups1-Mdm35 system, which mediates phosphatidic acid (PA) transfer between the outer and inner mitochondrial membranes, and determined the X-ray structures of Mdm35 and Ups1-Mdm35 with and without PA. The Ups1-Mdm35 complex constitutes a single domain that has a deep pocket and flexible Ω-loop lid. Structure-based mutational analyses revealed that a basic residue at the pocket bottom and the Ω-loop lid are important for PA extraction from the membrane following Ups1 binding. Ups1 binding to the membrane is enhanced by the dissociation of Mdm35. We also show that basic residues around the pocket entrance are important for Ups1 binding to the membrane and PA extraction. These results provide a structural basis for understanding the mechanism of PA transfer between mitochondrial membranes.

Plant Seeds as Model Vectors for the Transfer of Life Through Space

NASA Astrophysics Data System (ADS)

Tepfer, David; Leach, Sydney

2006-12-01

We consider plant seeds as terrestrial models for a vectored life form that could protect biological information in space. Seeds consist of maternal tissue surrounding and protecting an embryo. Some seeds resist deleterious conditions found in space: ultra low vacuum, extreme temperatures and radiation, including intense UV light. In a receptive environment, seeds could liberate a viable embryo, viable higher cells or a viable free-living organism (an endosymbiont or endophyte). Even if viability is lost, seeds still contain functional macro and small molecules (DNA, RNA, proteins, amino acids, lipids, etc.) that could provide the chemical basis for starting or modifying life. The possible release of endophytes or endosymbionts from a seed-like space traveler suggests that multiple domains of life, defined in DNA sequence phylogenies, could be disseminated simultaneously from Earth. We consider the possibility of exospermia, the outward transfer of life, as well as introspermia, the inward transfer of life-both as a contemporary and ancient events.

Analysis of simplified heat transfer models for thermal property determination of nano-film by TDTR method

NASA Astrophysics Data System (ADS)

Wang, Xinwei; Chen, Zhe; Sun, Fangyuan; Zhang, Hang; Jiang, Yuyan; Tang, Dawei

2018-03-01

Heat transfer in nanostructures is of critical importance for a wide range of applications such as functional materials and thermal management of electronics. Time-domain thermoreflectance (TDTR) has been proved to be a reliable measurement technique for the thermal property determinations of nanoscale structures. However, it is difficult to determine more than three thermal properties at the same time. Heat transfer model simplifications can reduce the fitting variables and provide an alternative way for thermal property determination. In this paper, two simplified models are investigated and analyzed by the transform matrix method and simulations. TDTR measurements are performed on Al-SiO2-Si samples with different SiO2 thickness. Both theoretical and experimental results show that the simplified tri-layer model (STM) is reliable and suitable for thin film samples with a wide range of thickness. Furthermore, the STM can also extract the intrinsic thermal conductivity and interfacial thermal resistance from serial samples with different thickness.

Discontinuous finite element method for vector radiative transfer

NASA Astrophysics Data System (ADS)

Wang, Cun-Hai; Yi, Hong-Liang; Tan, He-Ping

2017-03-01

The discontinuous finite element method (DFEM) is applied to solve the vector radiative transfer in participating media. The derivation in a discrete form of the vector radiation governing equations is presented, in which the angular space is discretized by the discrete-ordinates approach with a local refined modification, and the spatial domain is discretized into finite non-overlapped discontinuous elements. The elements in the whole solution domain are connected by modelling the boundary numerical flux between adjacent elements, which makes the DFEM numerically stable for solving radiative transfer equations. Several various problems of vector radiative transfer are tested to verify the performance of the developed DFEM, including vector radiative transfer in a one-dimensional parallel slab containing a Mie/Rayleigh/strong forward scattering medium and a two-dimensional square medium. The fact that DFEM results agree very well with the benchmark solutions in published references shows that the developed DFEM in this paper is accurate and effective for solving vector radiative transfer problems.

Functional innovation from changes in protein domains and their combinations.

PubMed

Lees, Jonathan G; Dawson, Natalie L; Sillitoe, Ian; Orengo, Christine A

2016-06-01

Domains are the functional building blocks of proteins. In this work we discuss how domains can contribute to the evolution of new functions. Domains themselves can evolve through various mechanisms, altering their intrinsic function. Domains can also facilitate functional innovations by combining with other domains to make novel proteins. We discuss the mechanisms by which domain and domain combinations support functional innovations. We highlight interesting examples where changes in domain combination promote changes at the domain level. Copyright © 2016 Elsevier Ltd. All rights reserved.

Direct geoelectrical evidence of mass transfer at the laboratory scale

NASA Astrophysics Data System (ADS)

Swanson, Ryan D.; Singha, Kamini; Day-Lewis, Frederick D.; Binley, Andrew; Keating, Kristina; Haggerty, Roy

2012-10-01

Previous field-scale experimental data and numerical modeling suggest that the dual-domain mass transfer (DDMT) of electrolytic tracers has an observable geoelectrical signature. Here we present controlled laboratory experiments confirming the electrical signature of DDMT and demonstrate the use of time-lapse electrical measurements in conjunction with concentration measurements to estimate the parameters controlling DDMT, i.e., the mobile and immobile porosity and rate at which solute exchanges between mobile and immobile domains. We conducted column tracer tests on unconsolidated quartz sand and a material with a high secondary porosity: the zeolite clinoptilolite. During NaCl tracer tests we collected nearly colocated bulk direct-current electrical conductivity (σb) and fluid conductivity (σf) measurements. Our results for the zeolite show (1) extensive tailing and (2) a hysteretic relation between σf and σb, thus providing evidence of mass transfer not observed within the quartz sand. To identify best-fit parameters and evaluate parameter sensitivity, we performed over 2700 simulations of σf, varying the immobile and mobile domain and mass transfer rate. We emphasized the fit to late-time tailing by minimizing the Box-Cox power transformed root-mean square error between the observed and simulated σf. Low-field proton nuclear magnetic resonance (NMR) measurements provide an independent quantification of the volumes of the mobile and immobile domains. The best-fit parameters based on σf match the NMR measurements of the immobile and mobile domain porosities and provide the first direct electrical evidence for DDMT. Our results underscore the potential of using electrical measurements for DDMT parameter inference.

Direct geoelectrical evidence of mass transfer at the laboratory scale

USGS Publications Warehouse

Swanson, Ryan D.; Singha, Kamini; Day-Lewis, Frederick D.; Binley, Andrew; Keating, Kristina; Haggerty, Roy

2012-01-01

Previous field-scale experimental data and numerical modeling suggest that the dual-domain mass transfer (DDMT) of electrolytic tracers has an observable geoelectrical signature. Here we present controlled laboratory experiments confirming the electrical signature of DDMT and demonstrate the use of time-lapse electrical measurements in conjunction with concentration measurements to estimate the parameters controlling DDMT, i.e., the mobile and immobile porosity and rate at which solute exchanges between mobile and immobile domains. We conducted column tracer tests on unconsolidated quartz sand and a material with a high secondary porosity: the zeolite clinoptilolite. During NaCl tracer tests we collected nearly colocated bulk direct-current electrical conductivity (σb) and fluid conductivity (σf) measurements. Our results for the zeolite show (1) extensive tailing and (2) a hysteretic relation between σf and σb, thus providing evidence of mass transfer not observed within the quartz sand. To identify best-fit parameters and evaluate parameter sensitivity, we performed over 2700 simulations of σf, varying the immobile and mobile domain and mass transfer rate. We emphasized the fit to late-time tailing by minimizing the Box-Cox power transformed root-mean square error between the observed and simulated σf. Low-field proton nuclear magnetic resonance (NMR) measurements provide an independent quantification of the volumes of the mobile and immobile domains. The best-fit parameters based on σf match the NMR measurements of the immobile and mobile domain porosities and provide the first direct electrical evidence for DDMT. Our results underscore the potential of using electrical measurements for DDMT parameter inference.

Molecular Evolution of the Oxygen-Binding Hemerythrin Domain

PubMed Central

Alvarez-Carreño, Claudia; Becerra, Arturo; Lazcano, Antonio

2016-01-01

Background The evolution of oxygenic photosynthesis during Precambrian times entailed the diversification of strategies minimizing reactive oxygen species-associated damage. Four families of oxygen-carrier proteins (hemoglobin, hemerythrin and the two non-homologous families of arthropodan and molluscan hemocyanins) are known to have evolved independently the capacity to bind oxygen reversibly, providing cells with strategies to cope with the evolutionary pressure of oxygen accumulation. Oxygen-binding hemerythrin was first studied in marine invertebrates but further research has made it clear that it is present in the three domains of life, strongly suggesting that its origin predated the emergence of eukaryotes. Results Oxygen-binding hemerythrins are a monophyletic sub-group of the hemerythrin/HHE (histidine, histidine, glutamic acid) cation-binding domain. Oxygen-binding hemerythrin homologs were unambiguously identified in 367/2236 bacterial, 21/150 archaeal and 4/135 eukaryotic genomes. Overall, oxygen-binding hemerythrin homologues were found in the same proportion as single-domain and as long protein sequences. The associated functions of protein domains in long hemerythrin sequences can be classified in three major groups: signal transduction, phosphorelay response regulation, and protein binding. This suggests that in many organisms the reversible oxygen-binding capacity was incorporated in signaling pathways. A maximum-likelihood tree of oxygen-binding hemerythrin homologues revealed a complex evolutionary history in which lateral gene transfer, duplications and gene losses appear to have played an important role. Conclusions Hemerythrin is an ancient protein domain with a complex evolutionary history. The distinctive iron-binding coordination site of oxygen-binding hemerythrins evolved first in prokaryotes, very likely prior to the divergence of Firmicutes and Proteobacteria, and spread into many bacterial, archaeal and eukaryotic species. The later evolution of the oxygen-binding hemerythrin domain in both prokaryotes and eukaryotes led to a wide variety of functions, ranging from protection against oxidative damage in anaerobic and microaerophilic organisms, to oxygen supplying to particular enzymes and pathways in aerobic and facultative species. PMID:27336621

Temperature-Dependent Function of the Glutamine Phosphoribosylpyrophosphate Amidotransferase Ammonia Channel and Coupling with Glycinamide Ribonucleotide Synthetase in a Hyperthermophile†

PubMed Central

Bera, Aloke Kumar; Chen, Sihong; Smith, Janet L.; Zalkin, Howard

2000-01-01

Genes encoding glutamine phosphoribosylpyrophosphate amidotransferase (GPAT) and glycinamide ribonucleotide synthetase (GARS) from Aquifex aeolicus were expressed in Escherichia coli, and the enzymes were purified to near homogeneity. Both enzymes were maximally active at a temperature of at least 90°C, with half-lives of 65 min for GPAT and 60 h for GARS at 80°C. GPAT activity is known to depend upon channeling of NH3 from a site in an N-terminal glutaminase domain to a distal phosphoribosylpyrophosphate site in a C-terminal domain where synthesis of phosphoribosylamine (PRA) takes place. The efficiency of channeling of NH3 for synthesis of PRA was found to increase from 34% at 37°C to a maximum of 84% at 80°C. The mechanism for transfer of PRA to GARS is not established, but diffusion between enzymes as a free intermediate appears unlikely based on a calculated PRA half-life of approximately 0.6 s at 90°C. Evidence was obtained for coupling between GPAT and GARS for PRA transfer. The coupling was temperature dependent, exhibiting a transition between 37 and 50°C, and remained relatively constant up to 90°C. The calculated PRA chemical half-life, however, decreased by a factor of 20 over this temperature range. These results provide evidence that coupling involves direct PRA transfer through GPAT-GARS interaction rather than free diffusion. PMID:10850988

Temperature-dependent function of the glutamine phosphoribosylpyrophosphate amidotransferase ammonia channel and coupling with glycinamide ribonucleotide synthetase in a hyperthermophile.

PubMed

Bera, A K; Chen, S; Smith, J L; Zalkin, H

2000-07-01

Genes encoding glutamine phosphoribosylpyrophosphate amidotransferase (GPAT) and glycinamide ribonucleotide synthetase (GARS) from Aquifex aeolicus were expressed in Escherichia coli, and the enzymes were purified to near homogeneity. Both enzymes were maximally active at a temperature of at least 90 degrees C, with half-lives of 65 min for GPAT and 60 h for GARS at 80 degrees C. GPAT activity is known to depend upon channeling of NH(3) from a site in an N-terminal glutaminase domain to a distal phosphoribosylpyrophosphate site in a C-terminal domain where synthesis of phosphoribosylamine (PRA) takes place. The efficiency of channeling of NH(3) for synthesis of PRA was found to increase from 34% at 37 degrees C to a maximum of 84% at 80 degrees C. The mechanism for transfer of PRA to GARS is not established, but diffusion between enzymes as a free intermediate appears unlikely based on a calculated PRA half-life of approximately 0.6 s at 90 degrees C. Evidence was obtained for coupling between GPAT and GARS for PRA transfer. The coupling was temperature dependent, exhibiting a transition between 37 and 50 degrees C, and remained relatively constant up to 90 degrees C. The calculated PRA chemical half-life, however, decreased by a factor of 20 over this temperature range. These results provide evidence that coupling involves direct PRA transfer through GPAT-GARS interaction rather than free diffusion.

Aerodynamic parameter estimation via Fourier modulating function techniques

NASA Technical Reports Server (NTRS)

Pearson, A. E.

1995-01-01

Parameter estimation algorithms are developed in the frequency domain for systems modeled by input/output ordinary differential equations. The approach is based on Shinbrot's method of moment functionals utilizing Fourier based modulating functions. Assuming white measurement noises for linear multivariable system models, an adaptive weighted least squares algorithm is developed which approximates a maximum likelihood estimate and cannot be biased by unknown initial or boundary conditions in the data owing to a special property attending Shinbrot-type modulating functions. Application is made to perturbation equation modeling of the longitudinal and lateral dynamics of a high performance aircraft using flight-test data. Comparative studies are included which demonstrate potential advantages of the algorithm relative to some well established techniques for parameter identification. Deterministic least squares extensions of the approach are made to the frequency transfer function identification problem for linear systems and to the parameter identification problem for a class of nonlinear-time-varying differential system models.

Crystal Structure of the Escherichia coli 23S rRNA: m{5}C Methyltransferase RlmI (YccW) Reveals Evolutionary Links Between RNA Modification Enzymes

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

Sunita, S.; Tkaczuk, K; Purta, E

2008-01-01

Methylation is the most common RNA modification in the three domains of life. Transfer of the methyl group from S-adenosyl-l-methionine (AdoMet) to specific atoms of RNA nucleotides is catalyzed by methyltransferase (MTase) enzymes. The rRNA MTase RlmI (rRNA large subunit methyltransferase gene I; previously known as YccW) specifically modifies Escherichia coli 23S rRNA at nucleotide C1962 to form 5-methylcytosine. Here, we report the crystal structure of RlmI refined at 2 {angstrom} to a final R-factor of 0.194 (R{sub free} = 0.242). The RlmI molecule comprises three domains: the N-terminal PUA domain; the central domain, which resembles a domain previously foundmore » in RNA:5-methyluridine MTases; and the C-terminal catalytic domain, which contains the AdoMet-binding site. The central and C-terminal domains are linked by a {Beta}-hairpin structure that has previously been observed in several MTases acting on nucleic acids or proteins. Based on bioinformatics analyses, we propose a model for the RlmI-AdoMet-RNA complex. Comparative structural analyses of RlmI and its homologs provide insight into the potential function of several structures that have been solved by structural genomics groups and furthermore indicate that the evolutionary paths of RNA and DNA 5-methyluridine and 5-methylcytosine MTases have been closely intertwined.« less

Design and evaluation of a THz time domain imaging system using standard optical design software.

PubMed

Brückner, Claudia; Pradarutti, Boris; Müller, Ralf; Riehemann, Stefan; Notni, Gunther; Tünnermann, Andreas

2008-09-20

A terahertz (THz) time domain imaging system is analyzed and optimized with standard optical design software (ZEMAX). Special requirements to the illumination optics and imaging optics are presented. In the optimized system, off-axis parabolic mirrors and lenses are combined. The system has a numerical aperture of 0.4 and is diffraction limited for field points up to 4 mm and wavelengths down to 750 microm. ZEONEX is used as the lens material. Higher aspherical coefficients are used for correction of spherical aberration and reduction of lens thickness. The lenses were manufactured by ultraprecision machining. For optimization of the system, ray tracing and wave-optical methods were combined. We show how the ZEMAX Gaussian beam analysis tool can be used to evaluate illumination optics. The resolution of the THz system was tested with a wire and a slit target, line gratings of different period, and a Siemens star. The behavior of the temporal line spread function can be modeled with the polychromatic coherent line spread function feature in ZEMAX. The spectral and temporal resolutions of the line gratings are compared with the respective modulation transfer function of ZEMAX. For maximum resolution, the system has to be diffraction limited down to the smallest wavelength of the spectrum of the THz pulse. Then, the resolution on time domain analysis of the pulse maximum can be estimated with the spectral resolution of the center of gravity wavelength. The system resolution near the optical axis on time domain analysis of the pulse maximum is 1 line pair/mm with an intensity contrast of 0.22. The Siemens star is used for estimation of the resolution of the whole system. An eight channel electro-optic sampling system was used for detection. The resolution on time domain analysis of the pulse maximum of all eight channels could be determined with the Siemens star to be 0.7 line pairs/mm.

Three-dimensional structure of NADPH–cytochrome P450 reductase: Prototype for FMN- and FAD-containing enzymes

PubMed Central

Wang, Ming; Roberts, David L.; Paschke, Rosemary; Shea, Thomas M.; Masters, Bettie Sue Siler; Kim, Jung-Ja P.

1997-01-01

Microsomal NADPH–cytochrome P450 reductase (CPR) is one of only two mammalian enzymes known to contain both FAD and FMN, the other being nitric-oxide synthase. CPR is a membrane-bound protein and catalyzes electron transfer from NADPH to all known microsomal cytochromes P450. The structure of rat liver CPR, expressed in Escherichia coli and solubilized by limited trypsinolysis, has been determined by x-ray crystallography at 2.6 Å resolution. The molecule is composed of four structural domains: (from the N- to C- termini) the FMN-binding domain, the connecting domain, and the FAD- and NADPH-binding domains. The FMN-binding domain is similar to the structure of flavodoxin, whereas the two C-terminal dinucleotide-binding domains are similar to those of ferredoxin–NADP+ reductase (FNR). The connecting domain, situated between the FMN-binding and FNR-like domains, is responsible for the relative orientation of the other domains, ensuring the proper alignment of the two flavins necessary for efficient electron transfer. The two flavin isoalloxazine rings are juxtaposed, with the closest distance between them being about 4 Å. The bowl-shaped surface near the FMN-binding site is likely the docking site of cytochrome c and the physiological redox partners, including cytochromes P450 and b5 and heme oxygenase. PMID:9237990

Using cognitive work analysis to explore activity allocation within military domains.

PubMed

Jenkins, D P; Stanton, N A; Salmon, P M; Walker, G H; Young, M S

2008-06-01

Cognitive work analysis (CWA) is frequently advocated as an approach for the analysis of complex socio-technical systems. Much of the current CWA literature within the military domain pays particular attention to its initial phases; work domain analysis and contextual task analysis. Comparably, the analysis of the social and organisational constraints receives much less attention. Through the study of a helicopter mission planning system software tool, this paper describes an approach for investigating the constraints affecting the distribution of work. The paper uses this model to evaluate the potential benefits of the social and organisational analysis phase within a military context. The analysis shows that, through its focus on constraints, the approach provides a unique description of the factors influencing the social organisation within a complex domain. This approach appears to be compatible with existing approaches and serves as a validation of more established social analysis techniques. As part of the ergonomic design of mission planning systems, the social organisation and cooperation analysis phase of CWA provides a constraint-based description informing allocation of function between key actor groups. This approach is useful because it poses questions related to the transfer of information and optimum working practices.

Neuromorphic log-domain silicon synapse circuits obey bernoulli dynamics: a unifying tutorial analysis

PubMed Central

Papadimitriou, Konstantinos I.; Liu, Shih-Chii; Indiveri, Giacomo; Drakakis, Emmanuel M.

2014-01-01

The field of neuromorphic silicon synapse circuits is revisited and a parsimonious mathematical framework able to describe the dynamics of this class of log-domain circuits in the aggregate and in a systematic manner is proposed. Starting from the Bernoulli Cell Formalism (BCF), originally formulated for the modular synthesis and analysis of externally linear, time-invariant logarithmic filters, and by means of the identification of new types of Bernoulli Cell (BC) operators presented here, a generalized formalism (GBCF) is established. The expanded formalism covers two new possible and practical combinations of a MOS transistor (MOST) and a linear capacitor. The corresponding mathematical relations codifying each case are presented and discussed through the tutorial treatment of three well-known transistor-level examples of log-domain neuromorphic silicon synapses. The proposed mathematical tool unifies past analysis approaches of the same circuits under a common theoretical framework. The speed advantage of the proposed mathematical framework as an analysis tool is also demonstrated by a compelling comparative circuit analysis example of high order, where the GBCF and another well-known log-domain circuit analysis method are used for the determination of the input-output transfer function of the high (4th) order topology. PMID:25653579

Neuromorphic log-domain silicon synapse circuits obey bernoulli dynamics: a unifying tutorial analysis.

PubMed

Papadimitriou, Konstantinos I; Liu, Shih-Chii; Indiveri, Giacomo; Drakakis, Emmanuel M

2014-01-01

The field of neuromorphic silicon synapse circuits is revisited and a parsimonious mathematical framework able to describe the dynamics of this class of log-domain circuits in the aggregate and in a systematic manner is proposed. Starting from the Bernoulli Cell Formalism (BCF), originally formulated for the modular synthesis and analysis of externally linear, time-invariant logarithmic filters, and by means of the identification of new types of Bernoulli Cell (BC) operators presented here, a generalized formalism (GBCF) is established. The expanded formalism covers two new possible and practical combinations of a MOS transistor (MOST) and a linear capacitor. The corresponding mathematical relations codifying each case are presented and discussed through the tutorial treatment of three well-known transistor-level examples of log-domain neuromorphic silicon synapses. The proposed mathematical tool unifies past analysis approaches of the same circuits under a common theoretical framework. The speed advantage of the proposed mathematical framework as an analysis tool is also demonstrated by a compelling comparative circuit analysis example of high order, where the GBCF and another well-known log-domain circuit analysis method are used for the determination of the input-output transfer function of the high (4(th)) order topology.

An improved ray theory and transfer matrix method-based model for lightning electromagnetic pulses propagating in Earth-ionosphere waveguide and its applications

NASA Astrophysics Data System (ADS)

Qin, Zilong; Chen, Mingli; Zhu, Baoyou; Du, Ya-ping

2017-01-01

An improved ray theory and transfer matrix method-based model for a lightning electromagnetic pulse (LEMP) propagating in Earth-ionosphere waveguide (EIWG) is proposed and tested. The model involves the presentation of a lightning source, parameterization of the lower ionosphere, derivation of a transfer function representing all effects of EIWG on LEMP sky wave, and determination of attenuation mode of the LEMP ground wave. The lightning source is simplified as an electric point dipole standing on Earth surface with finite conductance. The transfer function for the sky wave is derived based on ray theory and transfer matrix method. The attenuation mode for the ground wave is solved from Fock's diffraction equations. The model is then applied to several lightning sferics observed in central China during day and night times within 1000 km. The results show that the model can precisely predict the time domain sky wave for all these observed lightning sferics. Both simulations and observations show that the lightning sferics in nighttime has a more complicated waveform than in daytime. Particularly, when a LEMP propagates from east to west (Φ = 270°) and in nighttime, its sky wave tends to be a double-peak waveform (dispersed sky wave) rather than a single peak one. Such a dispersed sky wave in nighttime may be attributed to the magneto-ionic splitting phenomenon in the lower ionosphere. The model provides us an efficient way for retrieving the electron density profile of the lower ionosphere and hence to monitor its spatial and temporal variations via lightning sferics.

INCA- INTERACTIVE CONTROLS ANALYSIS

NASA Technical Reports Server (NTRS)

Bauer, F. H.

1994-01-01

The Interactive Controls Analysis (INCA) program was developed to provide a user friendly environment for the design and analysis of linear control systems, primarily feedback control systems. INCA is designed for use with both small and large order systems. Using the interactive graphics capability, the INCA user can quickly plot a root locus, frequency response, or time response of either a continuous time system or a sampled data system. The system configuration and parameters can be easily changed, allowing the INCA user to design compensation networks and perform sensitivity analysis in a very convenient manner. A journal file capability is included. This stores an entire sequence of commands, generated during an INCA session into a file which can be accessed later. Also included in INCA are a context-sensitive help library, a screen editor, and plot windows. INCA is robust to VAX-specific overflow problems. The transfer function is the basic unit of INCA. Transfer functions are automatically saved and are available to the INCA user at any time. A powerful, user friendly transfer function manipulation and editing capability is built into the INCA program. The user can do all transfer function manipulations and plotting without leaving INCA, although provisions are made to input transfer functions from data files. By using a small set of commands, the user may compute and edit transfer functions, and then examine these functions by using the ROOT_LOCUS, FREQUENCY_RESPONSE, and TIME_RESPONSE capabilities. Basic input data, including gains, are handled as single-input single-output transfer functions. These functions can be developed using the function editor or by using FORTRAN- like arithmetic expressions. In addition to the arithmetic functions, special functions are available to 1) compute step, ramp, and sinusoid functions, 2) compute closed loop transfer functions, 3) convert from S plane to Z plane with optional advanced Z transform, and 4) convert from Z plane to W plane and back. These capabilities allow the INCA user to perform block diagram algebraic manipulations quickly for functions in the S, Z, and W domains. Additionally, a versatile digital control capability has been included in INCA. Special plane transformations allow the user to easily convert functions from one domain to another. Other digital control capabilities include: 1) totally independent open loop frequency response analyses on a continuous plant, discrete control system with a delay, 2) advanced Z-transform capability for systems with delays, and 3) multirate sampling analyses. The current version of INCA includes Dynamic Functions (which change when a parameter changes), standard filter generation, PD and PID controller generation, incorporation of the QZ-algorithm (function addition, inverse Laplace), and describing functions that allow the user to calculate the gain and phase characteristics of a nonlinear device. The INCA graphic modes provide the user with a convenient means to document and study frequency response, time response, and root locus analyses. General graphics features include: 1) zooming and dezooming, 2) plot documentation, 3) a table of analytic computation results, 4) multiple curves on the same plot, and 5) displaying frequency and gain information for a specific point on a curve. Additional capabilities in the frequency response mode include: 1) a full complement of graphical methods Bode magnitude, Bode phase, Bode combined magnitude and phase, Bode strip plots, root contour plots, Nyquist, Nichols, and Popov plots; 2) user selected plot scaling; and 3) gain and phase margin calculation and display. In the time response mode, additional capabilities include: 1) support for inverse Laplace and inverse Z transforms, 2) support for various input functions, 3) closed loop response evaluation, 4) loop gain sensitivity analyses, 5) intersample time response for discrete systems using the advanced Z transform, and 6) closed loop time response using mixed plane (S, Z, W) operations with delay. A Graphics mode command was added to the current version of INCA, version 3.13, to produce Metafiles (graphic files) of the currently displayed plot. The metafile can be displayed and edited using the QPLOT Graphics Editor and Replotter for Metafiles (GERM) program included with the INCA package. The INCA program is written in Pascal and FORTRAN for interactive or batch execution and has been implemented on a DEC VAX series computer under VMS. Both source code and executable code are supplied for INCA. Full INCA graphics capabilities are supported for various Tektronix 40xx and 41xx terminals; DEC VT graphics terminals; many PC and Macintosh terminal emulators; TEK014 hardcopy devices such as the LN03 Laserprinter; and bit map graphics external hardcopy devices. Also included for the TEK4510 rasterizer users are a multiple copy feature, a wide line feature, and additional graphics fonts. The INCA program was developed in 1985, Version 2.04 was released in 1986, Version 3.00 was released in 1988, and Version 3.13 was released in 1989. An INCA version 2.0X conversion program is included.

Spectral analysis for nonstationary and nonlinear systems: a discrete-time-model-based approach.

PubMed

He, Fei; Billings, Stephen A; Wei, Hua-Liang; Sarrigiannis, Ptolemaios G; Zhao, Yifan

2013-08-01

A new frequency-domain analysis framework for nonlinear time-varying systems is introduced based on parametric time-varying nonlinear autoregressive with exogenous input models. It is shown how the time-varying effects can be mapped to the generalized frequency response functions (FRFs) to track nonlinear features in frequency, such as intermodulation and energy transfer effects. A new mapping to the nonlinear output FRF is also introduced. A simulated example and the application to intracranial electroencephalogram data are used to illustrate the theoretical results.

Monitoring glycolipid transfer protein activity and membrane interaction with the surface plasmon resonance technique.

PubMed

Ohvo-Rekilä, Henna; Mattjus, Peter

2011-01-01

The glycolipid transfer protein (GLTP) is a protein capable of binding and transferring glycolipids. GLTP is cytosolic and it can interact through its FFAT-like (two phenylalanines in an acidic tract) motif with proteins localized on the surface of the endoplasmic reticulum. Previous in vitro work with GLTP has focused mainly on the complete transfer reaction of the protein, that is, binding and subsequent removal of the glycolipid from the donor membrane, transfer through the aqueous environment, and the final release of the glycolipid to an acceptor membrane. Using bilayer vesicles and surface plasmon resonance spectroscopy, we have now, for the first time, analyzed the binding and lipid removal capacity of GLTP with a completely label-free technique. This technique is focused on the initial steps in GLTP-mediated transfer and the parameters affecting these steps can be more precisely determined. We used the new approach for detailed structure-function studies of GLTP by examining the glycolipid transfer capacity of specific GLTP tryptophan mutants. Tryptophan 96 is crucial for the transfer activity of the protein and tryptophan 142 is an important part of the proteins membrane interacting domain. Further, we varied the composition of the used lipid vesicles and gained information on the effect of membrane properties on GLTP activity. GLTP prefers to interact with more tightly packed membranes, although GLTP-mediated transfer is faster from more fluid membranes. This technique is very useful for the study of membrane-protein interactions and lipid-transfer rates and it can easily be adapted to other membrane-interacting proteins. Copyright © 2010 Elsevier B.V. All rights reserved.

Belief and sign, true and false: the unique of false belief reasoning.

PubMed

Zhang, Ting; Zhang, Qin; Li, Yiyuan; Long, Changquan; Li, Hong

2013-11-01

For a long time, a controversy has been proposed that whether the process of theory of mind is a result of domain-specific or domain-general changes (Wellman in The handbook of childhood cognitive development. Blackwell Publication, New Jersey, 2011). This event-related potential study explored the neural time course of domain-general and domain-specific components in belief reasoning. Fourteen participants completed location transfer false belief (FB), true belief (TB), false sign (FS) and true sign (TS) tasks, in which two pictures told a story related to a dog that ran from a green into a red box. In the TB and FB tasks, a boy saw or did not see the transfer of the dog, respectively. In the FS and TS tasks, an arrow that pointed to the green box either altered its direction to the red box or did not alter following the transfer of the dog. Participants then inferred where the boy thought of, or the arrow indicated the location of the dog. FB and TB reasoning elicited lower N2 amplitudes than FS and TS reasoning, which is associated with domain-general components, the detection, and classification. The late slow wave (LSW) for FB was more positive at frontal, central, and parietal sites than FS because of the domain-specific component involved in FB reasoning. However, the LSW was less positive for TB than for FB but did not differ from the TS condition, which implies that mental representation might not be involved in TB reasoning.

Dynamics of magnetization in ferromagnet with spin-transfer torque

NASA Astrophysics Data System (ADS)

Li, Zai-Dong; He, Peng-Bin; Liu, Wu-Ming

2014-11-01

We review our recent works on dynamics of magnetization in ferromagnet with spin-transfer torque. Driven by constant spin-polarized current, the spin-transfer torque counteracts both the precession driven by the effective field and the Gilbert damping term different from the common understanding. When the spin current exceeds the critical value, the conjunctive action of Gilbert damping and spin-transfer torque leads naturally the novel screw-pitch effect characterized by the temporal oscillation of domain wall velocity and width. Driven by space- and time-dependent spin-polarized current and magnetic field, we expatiate the formation of domain wall velocity in ferromagnetic nanowire. We discuss the properties of dynamic magnetic soliton in uniaxial anisotropic ferromagnetic nanowire driven by spin-transfer torque, and analyze the modulation instability and dark soliton on the spin wave background, which shows the characteristic breather behavior of the soliton as it propagates along the ferromagnetic nanowire. With stronger breather character, we get the novel magnetic rogue wave and clarify its formation mechanism. The generation of magnetic rogue wave mainly arises from the accumulation of energy and magnons toward to its central part. We also observe that the spin-polarized current can control the exchange rate of magnons between the envelope soliton and the background, and the critical current condition is obtained analytically. At last, we have theoretically investigated the current-excited and frequency-adjusted ferromagnetic resonance in magnetic trilayers. A particular case of the perpendicular analyzer reveals that the ferromagnetic resonance curves, including the resonant location and the resonant linewidth, can be adjusted by changing the pinned magnetization direction and the direct current. Under the control of the current and external magnetic field, several magnetic states, such as quasi-parallel and quasi-antiparallel stable states, out-of-plane precession, and bistable states can be realized. The precession frequency can be expressed as a function of the current and external magnetic field.

A Bacterial Multidomain NAD-Independent d-Lactate Dehydrogenase Utilizes Flavin Adenine Dinucleotide and Fe-S Clusters as Cofactors and Quinone as an Electron Acceptor for d-Lactate Oxidization

PubMed Central

Jiang, Tianyi; Guo, Xiaoting; Yan, Jinxin; Zhang, Yingxin; Wang, Yujiao; Zhang, Manman; Sheng, Binbin; Ma, Cuiqing; Xu, Ping

2017-01-01

ABSTRACT Bacterial membrane-associated NAD-independent d-lactate dehydrogenase (Fe-S d-iLDH) oxidizes d-lactate into pyruvate. A sequence analysis of the enzyme reveals that it contains an Fe-S oxidoreductase domain in addition to a flavin adenine dinucleotide (FAD)-containing dehydrogenase domain, which differs from other typical d-iLDHs. Fe-S d-iLDH from Pseudomonas putida KT2440 was purified as a His-tagged protein and characterized in detail. This monomeric enzyme exhibited activities with l-lactate and several d-2-hydroxyacids. Quinone was shown to be the preferred electron acceptor of the enzyme. The two domains of the enzyme were then heterologously expressed and purified separately. The Fe-S cluster-binding motifs predicted by sequence alignment were preliminarily verified by site-directed mutagenesis of the Fe-S oxidoreductase domain. The FAD-containing dehydrogenase domain retained 2-hydroxyacid-oxidizing activity, although it decreased compared to the full Fe-S d-iLDH. Compared to the intact enzyme, the FAD-containing dehydrogenase domain showed increased catalytic efficiency with cytochrome c as the electron acceptor, but it completely lost the ability to use coenzyme Q10. Additionally, the FAD-containing dehydrogenase domain was no longer associated with the cell membrane, and it could not support the utilization of d-lactate as a carbon source. Based on the results obtained, we conclude that the Fe-S oxidoreductase domain functions as an electron transfer component to facilitate the utilization of quinone as an electron acceptor by Fe-S d-iLDH, and it helps the enzyme associate with the cell membrane. These functions make the Fe-S oxidoreductase domain crucial for the in vivo d-lactate utilization function of Fe-S d-iLDH. IMPORTANCE Lactate metabolism plays versatile roles in most domains of life. Lactate utilization processes depend on certain enzymes to oxidize lactate to pyruvate. In recent years, novel bacterial lactate-oxidizing enzymes have been continually reported, including the unique NAD-independent d-lactate dehydrogenase that contains an Fe-S oxidoreductase domain besides the typical flavin-containing domain (Fe-S d-iLDH). Although Fe-S d-iLDH is widely distributed among bacterial species, the investigation of it is insufficient. Fe-S d-iLDH from Pseudomonas putida KT2440, which is the major d-lactate-oxidizing enzyme for the strain, might be a representative of this type of enzyme. A study of it will be helpful in understanding the detailed mechanisms underlying the lactate utilization processes. PMID:28847921

Conserved aspartate and lysine residues of RcsB are required for amylovoran biosynthesis, virulence, and DNA binding in Erwinia amylovora.

PubMed

Ancona, Veronica; Chatnaparat, Tiyakhon; Zhao, Youfu

2015-08-01

In Erwinia amylovora, the Rcs phosphorelay system is essential for amylovoran production and virulence. To further understand the role of conserved aspartate residue (D56) in the phosphor receiver (PR) domain and lysine (K180) residue in the function domain of RcsB, amino acid substitutions of RcsB mutant alleles were generated by site-directed mutagenesis and complementation of various rcs mutants were performed. A D56E substitution of RcsB, which mimics the phosphorylation state of RcsB, complemented the rcsB mutant, resulting in increased amylovoran production and gene expression, reduced swarming motility, and restored pathogenicity. In contrast, D56N and K180A or K180Q substitutions of RcsB did not complement the rcsB mutant. Electrophoresis mobility shift assays showed that D56E, but not D56N, K180Q and K180A substitutions of RcsB bound to promoters of amsG and flhD, indicating that both D56 and K180 are required for DNA binding. Interestingly, the RcsBD56E allele could also complement rcsAB, rcsBC and rcsABCD mutants with restored virulence and increased amylovoran production, indicating that RcsB phosphorylation is essential for virulence of E. amylovora. In addition, mutations of T904 and A905, but not phosphorylation mimic mutation of D876 in the PR domain of RcsC, constitutively activate the Rcs system, suggesting that phosphor transfer is required for activating the Rcs system and indicating both A905 and T904 are required for the phosphatase activity of RcsC. Our results demonstrated that RcsB phosphorylation and dephosphorylation, phosphor transfer from RcsC are essential for the function of the Rcs system, and also suggested that constitutive activation of the Rcs system could reduce the fitness of E. amylovora.

The C-terminal cytidine deaminase domain of APOBEC3G itself undergoes intersegmental transfer for a target search, as revealed by real-time NMR monitoring.

PubMed

Kamba, Keisuke; Nagata, Takashi; Katahira, Masato

2018-01-31

APOBEC3G (A3G), an anti-human immunodeficiency virus 1 factor, deaminates cytidines. We examined deamination of two cytidines located separately on substrate ssDNA by the C-terminal domain (CTD) of A3G using real-time NMR monitoring. The deamination preference between the two cytidines was lost when either the substrate or non-substrate ssDNA concentration increased. When the non-substrate ssDNA concentration increased, the deamination activity first increased, but then decreased. This indicates that even a single domain, A3G-CTD, undergoes intersegmental transfer for a target search.

A domain-centric solution to functional genomics via dcGO Predictor

PubMed Central

2013-01-01

Background Computational/manual annotations of protein functions are one of the first routes to making sense of a newly sequenced genome. Protein domain predictions form an essential part of this annotation process. This is due to the natural modularity of proteins with domains as structural, evolutionary and functional units. Sometimes two, three, or more adjacent domains (called supra-domains) are the operational unit responsible for a function, e.g. via a binding site at the interface. These supra-domains have contributed to functional diversification in higher organisms. Traditionally functional ontologies have been applied to individual proteins, rather than families of related domains and supra-domains. We expect, however, to some extent functional signals can be carried by protein domains and supra-domains, and consequently used in function prediction and functional genomics. Results Here we present a domain-centric Gene Ontology (dcGO) perspective. We generalize a framework for automatically inferring ontological terms associated with domains and supra-domains from full-length sequence annotations. This general framework has been applied specifically to primary protein-level annotations from UniProtKB-GOA, generating GO term associations with SCOP domains and supra-domains. The resulting 'dcGO Predictor', can be used to provide functional annotation to protein sequences. The functional annotation of sequences in the Critical Assessment of Function Annotation (CAFA) has been used as a valuable opportunity to validate our method and to be assessed by the community. The functional annotation of all completely sequenced genomes has demonstrated the potential for domain-centric GO enrichment analysis to yield functional insights into newly sequenced or yet-to-be-annotated genomes. This generalized framework we have presented has also been applied to other domain classifications such as InterPro and Pfam, and other ontologies such as mammalian phenotype and disease ontology. The dcGO and its predictor are available at http://supfam.org/SUPERFAMILY/dcGO including an enrichment analysis tool. Conclusions As functional units, domains offer a unique perspective on function prediction regardless of whether proteins are multi-domain or single-domain. The 'dcGO Predictor' holds great promise for contributing to a domain-centric functional understanding of genomes in the next generation sequencing era. PMID:23514627

Domain wall dynamics along curved strips under current pulses: The influence of Joule heating

NASA Astrophysics Data System (ADS)

Raposo, Victor; Moretti, Simone; Hernandez, Maria Auxiliadora; Martinez, Eduardo

2016-01-01

The current-induced domain wall dynamics along curved ferromagnetic strips is studied by coupling the magnetization dynamics to the heat transport. Permalloy strips with uniform and non-uniform cross section are evaluated, taking into account the influence of the electrical contacts used to inject the current pulses and the substrate on top of which the ferromagnetic strip is sited. Micromagnetic simulations indicate that the geometry and the non-ferromagnetic materials in the system play a significant role in the current-induced domain wall dynamics. Due to the natural pinning, domain walls are hardly affected by the spin-transfer torques when placed in uniform cross section strips under current pulses with reduced magnitude. On the contrary, the current-induced domain wall displacement is significantly different in strips with non-uniform cross section, where thermal gradients emerge as due to the Joule heating. It is found that these thermal gradients can assist or act against the pure spin-transfer torques, in agreement with the recent experimental observations.

Structural and Functional insights into the catalytic mechanism of the Type II NADH:quinone oxidoreductase family

PubMed Central

Marreiros, Bruno C.; Sena, Filipa V.; Sousa, Filipe M.; Oliveira, A. Sofia F.; Soares, Cláudio M.; Batista, Ana P.; Pereira, Manuela M.

2017-01-01

Type II NADH:quinone oxidoreductases (NDH-2s) are membrane proteins involved in respiratory chains. These proteins contribute indirectly to the establishment of the transmembrane difference of electrochemical potential by catalyzing the reduction of quinone by oxidation of NAD(P)H. NDH-2s are widespread enzymes being present in the three domains of life. In this work, we explored the catalytic mechanism of NDH-2 by investigating the common elements of all NDH-2s, based on the rationale that conservation of such elements reflects their structural/functional importance. We observed conserved sequence motifs and structural elements among 1762 NDH-2s. We identified two proton pathways possibly involved in the protonation of the quinone. Our results led us to propose the first catalytic mechanism for NDH-2 family, in which a conserved glutamate residue, E172 (in NDH-2 from Staphylococcus aureus) plays a key role in proton transfer to the quinone pocket. This catalytic mechanism may also be extended to the other members of the two-Dinucleotide Binding Domains Flavoprotein (tDBDF) superfamily, such as sulfide:quinone oxidoreductases. PMID:28181562

Mapping of voltage sensor positions in resting and inactivated mammalian sodium channels by LRET

PubMed Central

Kubota, Tomoya; Durek, Thomas; Dang, Bobo; Finol-Urdaneta, Rocio K.; Craik, David J.; Kent, Stephen B. H.; French, Robert J.; Bezanilla, Francisco; Correa, Ana M.

2017-01-01

Voltage-gated sodium channels (Navs) play crucial roles in excitable cells. Although vertebrate Nav function has been extensively studied, the detailed structural basis for voltage-dependent gating mechanisms remain obscure. We have assessed the structural changes of the Nav voltage sensor domain using lanthanide-based resonance energy transfer (LRET) between the rat skeletal muscle voltage-gated sodium channel (Nav1.4) and fluorescently labeled Nav1.4-targeting toxins. We generated donor constructs with genetically encoded lanthanide-binding tags (LBTs) inserted at the extracellular end of the S4 segment of each domain (with a single LBT per construct). Three different Bodipy-labeled, Nav1.4-targeting toxins were synthesized as acceptors: β-scorpion toxin (Ts1)-Bodipy, KIIIA-Bodipy, and GIIIA-Bodipy analogs. Functional Nav-LBT channels expressed in Xenopus oocytes were voltage-clamped, and distinct LRET signals were obtained in the resting and slow inactivated states. Intramolecular distances computed from the LRET signals define a geometrical map of Nav1.4 with the bound toxins, and reveal voltage-dependent structural changes related to channel gating. PMID:28202723

Observatory geoelectric fields induced in a two-layer lithosphere during magnetic storms

USGS Publications Warehouse

Love, Jeffrey J.; Swidinsky, Andrei

2015-01-01

We report on the development and validation of an algorithm for estimating geoelectric fields induced in the lithosphere beneath an observatory during a magnetic storm. To accommodate induction in three-dimensional lithospheric electrical conductivity, we analyze a simple nine-parameter model: two horizontal layers, each with uniform electrical conductivity properties given by independent distortion tensors. With Laplace transformation of the induction equations into the complex frequency domain, we obtain a transfer function describing induction of observatory geoelectric fields having frequency-dependent polarization. Upon inverse transformation back to the time domain, the convolution of the corresponding impulse-response function with a geomagnetic time series yields an estimated geoelectric time series. We obtain an optimized set of conductivity parameters using 1-s resolution geomagnetic and geoelectric field data collected at the Kakioka, Japan, observatory for five different intense magnetic storms, including the October 2003 Halloween storm; our estimated geoelectric field accounts for 93% of that measured during the Halloween storm. This work demonstrates the need for detailed modeling of the Earth’s lithospheric conductivity structure and the utility of co-located geomagnetic and geoelectric monitoring.

Mapping of voltage sensor positions in resting and inactivated mammalian sodium channels by LRET.

PubMed

Kubota, Tomoya; Durek, Thomas; Dang, Bobo; Finol-Urdaneta, Rocio K; Craik, David J; Kent, Stephen B H; French, Robert J; Bezanilla, Francisco; Correa, Ana M

2017-03-07

Voltage-gated sodium channels (Navs) play crucial roles in excitable cells. Although vertebrate Nav function has been extensively studied, the detailed structural basis for voltage-dependent gating mechanisms remain obscure. We have assessed the structural changes of the Nav voltage sensor domain using lanthanide-based resonance energy transfer (LRET) between the rat skeletal muscle voltage-gated sodium channel (Nav1.4) and fluorescently labeled Nav1.4-targeting toxins. We generated donor constructs with genetically encoded lanthanide-binding tags (LBTs) inserted at the extracellular end of the S4 segment of each domain (with a single LBT per construct). Three different Bodipy-labeled, Nav1.4-targeting toxins were synthesized as acceptors: β-scorpion toxin (Ts1)-Bodipy, KIIIA-Bodipy, and GIIIA-Bodipy analogs. Functional Nav-LBT channels expressed in Xenopus oocytes were voltage-clamped, and distinct LRET signals were obtained in the resting and slow inactivated states. Intramolecular distances computed from the LRET signals define a geometrical map of Nav1.4 with the bound toxins, and reveal voltage-dependent structural changes related to channel gating.

Triangular node for Transmission-Line Modeling (TLM) applied to bio-heat transfer.

PubMed

Milan, Hugo F M; Gebremedhin, Kifle G

2016-12-01

Transmission-Line Modeling (TLM) is a numerical method used to solve complex and time-domain bio-heat transfer problems. In TLM, rectangles are used to discretize two-dimensional problems. The drawback in using rectangular shapes is that instead of refining only the domain of interest, a large additional domain will also be refined in the x and y axes, which results in increased computational time and memory space. In this paper, we developed a triangular node for TLM applied to bio-heat transfer that does not have the drawback associated with the rectangular nodes. The model includes heat source, blood perfusion (advection), boundary conditions and initial conditions. The boundary conditions could be adiabatic, temperature, heat flux, or convection. A matrix equation for TLM, which simplifies the solution of time-domain problems or solves steady-state problems, was also developed. The predicted results were compared against results obtained from the solution of a simplified two-dimensional problem, and they agreed within 1% for a mesh length of triangular faces of 59µm±9µm (mean±standard deviation) and a time step of 1ms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Förster resonance energy transfer (FRET)-based picosecond lifetime reference for instrument response evaluation

NASA Astrophysics Data System (ADS)

Luchowski, R.; Kapusta, P.; Szabelski, M.; Sarkar, P.; Borejdo, J.; Gryczynski, Z.; Gryczynski, I.

2009-09-01

Förster resonance energy transfer (FRET) can be utilized to achieve ultrashort fluorescence responses in time-domain fluorometry. In a poly(vinyl) alcohol matrix, the presence of 60 mM Rhodamine 800 acceptor shortens the fluorescence lifetime of a pyridine 1 donor to about 20 ps. Such a fast fluorescence response is very similar to the instrument response function (IRF) obtained using scattered excitation light. A solid fluorescent sample (e.g a film) with picosecond lifetime is ideal for IRF measurements and particularly useful for time-resolved microscopy. Avalanche photodiode detectors, commonly used in this field, feature color- dependent-timing responses. We demonstrate that recording the fluorescence decay of the proposed FRET-based reference sample yields a better IRF approximation than the conventional light-scattering method and therefore avoids systematic errors in decay curve analysis.

Fourier-domain study of drift turbulence driven sheared flow in a laboratory plasma

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

Xu, M.; Tynan, G. R.; Holland, C.

2010-03-15

Frequency-resolved nonlinear internal and kinetic energy transfer rates have been measured in the Controlled Shear Decorrelation Experiment (CSDX) linear plasma device using a recently developed technique [Xu et al., Phys. Plasmas 16, 042312 (2009)]. The results clearly show a net kinetic energy transfer into the zonal flow frequency region, consistent with previous time-domain observations of turbulence-driven shear flows [Tynan et al., Plasma Phys. Controlled Fusion 48, S51 (2006)]. The experimentally measured dispersion relation has been used to map the frequency-resolved energy transfer rates into the wave number domain, which shows that the shear flow drive comes from midrange (k{sub t}hetarho{submore » S}>0.3) drift fluctuations, and the strongest flow drive comes from k{sub t}hetarho{sub S}approx =1 fluctuations. Linear growth rates have been inferred from a linearized Hasegawa-Wakatani model [Hasegawa et al., Phys. Fluids 22, 2122 (1979)], which indicates that the m=0 mode is linearly stable and the m=1-10 modes (corresponding to k{sub t}hetarho{sub S}>0.3) are linearly unstable for the n=1 and n=2 radial eigenmodes. This is consistent with our energy transfer measurements.« less

The structural role of the zinc ion can be dispensable in prokaryotic zinc-finger domains

PubMed Central

Baglivo, Ilaria; Russo, Luigi; Esposito, Sabrina; Malgieri, Gaetano; Renda, Mario; Salluzzo, Antonio; Di Blasio, Benedetto; Isernia, Carla; Fattorusso, Roberto; Pedone, Paolo V.

2009-01-01

The recent characterization of the prokaryotic Cys2His2 zinc-finger domain, identified in Ros protein from Agrobacterium tumefaciens, has demonstrated that, although possessing a similar zinc coordination sphere, this domain is structurally very different from its eukaryotic counterpart. A search in the databases has identified ≈300 homologues with a high sequence identity to the Ros protein, including the amino acids that form the extensive hydrophobic core in Ros. Surprisingly, the Cys2His2 zinc coordination sphere is generally poorly conserved in the Ros homologues, raising the question of whether the zinc ion is always preserved in these proteins. Here, we present a functional and structural study of a point mutant of Ros protein, Ros56–142C82D, in which the second coordinating cysteine is replaced by an aspartate, 5 previously-uncharacterized representative Ros homologues from Mesorhizobium loti, and 2 mutants of the homologues. Our results indicate that the prokaryotic zinc-finger domain, which in Ros protein tetrahedrally coordinates Zn(II) through the typical Cys2His2 coordination, in Ros homologues can either exploit a CysAspHis2 coordination sphere, previously never described in DNA binding zinc finger domains to our knowledge, or lose the metal, while still preserving the DNA-binding activity. We demonstrate that this class of prokaryotic zinc-finger domains is structurally very adaptable, and surprisingly single mutations can transform a zinc-binding domain into a nonzinc-binding domain and vice versa, without affecting the DNA-binding ability. In light of our findings an evolutionary link between the prokaryotic and eukaryotic zinc-finger domains, based on bacteria-to-eukaryota horizontal gene transfer, is discussed. PMID:19369210

An Exploration Of Fuel Optimal Two-impulse Transfers To Cyclers in the Earth-Moon System

NASA Astrophysics Data System (ADS)

Hosseinisianaki, Saghar

2011-12-01

This research explores the optimum two-impulse transfers between a low Earth orbit and cycler orbits in the Earth-Moon circular restricted three-body framework, emphasizing the optimization strategy. Cyclers are those types of periodic orbits that meet both the Earth and the Moon periodically. A spacecraft on such trajectories are under the influence of both the Earth and the Moon gravitational fields. Cyclers have gained recent interest as baseline orbits for several Earth-Moon mission concepts, notably in relation to human exploration. In this thesis it is shown that a direct optimization starting from the classic lambert initial guess may not be adequate for these problems and propose a three-step optimization solver to improve the domain of convergence toward an optimal solution. The first step consists of finding feasible trajectories with a given transfer time. I employ Lambert's problem to provide initial guess to optimize the error in arrival position. This includes the analysis of the liability of Lambert's solution as an initial guess. Once a feasible trajectory is found, the velocity impulse is only a function of transfer time, departure, and arrival points' phases. The second step consists of the optimization of impulse over transfer time which results in the minimum impulse transfer for fixed end points. Finally, the third step is mapping the optimal solutions as the end points are varied.

An Exploration Of Fuel Optimal Two-impulse Transfers To Cyclers in the Earth-Moon System

NASA Astrophysics Data System (ADS)

Hosseinisianaki, Saghar

This research explores the optimum two-impulse transfers between a low Earth orbit and cycler orbits in the Earth-Moon circular restricted three-body framework, emphasizing the optimization strategy. Cyclers are those types of periodic orbits that meet both the Earth and the Moon periodically. A spacecraft on such trajectories are under the influence of both the Earth and the Moon gravitational fields. Cyclers have gained recent interest as baseline orbits for several Earth-Moon mission concepts, notably in relation to human exploration. In this thesis it is shown that a direct optimization starting from the classic lambert initial guess may not be adequate for these problems and propose a three-step optimization solver to improve the domain of convergence toward an optimal solution. The first step consists of finding feasible trajectories with a given transfer time. I employ Lambert's problem to provide initial guess to optimize the error in arrival position. This includes the analysis of the liability of Lambert's solution as an initial guess. Once a feasible trajectory is found, the velocity impulse is only a function of transfer time, departure, and arrival points' phases. The second step consists of the optimization of impulse over transfer time which results in the minimum impulse transfer for fixed end points. Finally, the third step is mapping the optimal solutions as the end points are varied.

Potential Functional Replacement of the Plastidic Acetyl-CoA Carboxylase Subunit (accD) Gene by Recent Transfers to the Nucleus in Some Angiosperm Lineages1[W][OA

PubMed Central

Rousseau-Gueutin, Mathieu; Huang, Xun; Higginson, Emily; Ayliffe, Michael; Day, Anil; Timmis, Jeremy N.

2013-01-01

Eukaryotic cells originated when an ancestor of the nucleated cell engulfed bacterial endosymbionts that gradually evolved into the mitochondrion and the chloroplast. Soon after these endosymbiotic events, thousands of ancestral prokaryotic genes were functionally transferred from the endosymbionts to the nucleus. This process of functional gene relocation, now rare in eukaryotes, continues in angiosperms. In this article, we show that the chloroplastic acetyl-CoA carboxylase subunit (accD) gene that is present in the plastome of most angiosperms has been functionally relocated to the nucleus in the Campanulaceae. Surprisingly, the nucleus-encoded accD transcript is considerably smaller than the plastidic version, consisting of little more than the carboxylase domain of the plastidic accD gene fused to a coding region encoding a plastid targeting peptide. We verified experimentally the presence of a chloroplastic transit peptide by showing that the product of the nuclear accD fused to green fluorescent protein was imported in the chloroplasts. The nuclear gene regulatory elements that enabled the erstwhile plastidic gene to become functional in the nuclear genome were identified, and the evolution of the intronic and exonic sequences in the nucleus is described. Relocation and truncation of the accD gene is a remarkable example of the processes underpinning endosymbiotic evolution. PMID:23435694

Hierarchically Patterned Noncovalent Functionalization of 2D Materials by Controlled Langmuir-Schaefer Conversion.

PubMed

Davis, Tyson C; Bang, Jae Jin; Brooks, Jacob T; McMillan, David G; Claridge, Shelley A

2018-01-30

Noncovalent monolayer chemistries are often used to functionalize 2D materials. Nanoscopic ligand ordering has been widely demonstrated (e.g., lying-down lamellar phases of functional alkanes); however, combining this control with micro- and macroscopic patterning for practical applications remains a significant challenge. A few reports have demonstrated that standing phase Langmuir films on water can be converted into nanoscopic lying-down molecular domains on 2D substrates (e.g., graphite), using horizontal dipping (Langmuir-Schaefer, LS, transfer). Molecular patterns are known to form at scales up to millimeters in Langmuir films, suggesting the possibility of transforming such structures into functional patterns on 2D materials. However, to our knowledge, this approach has not been investigated, and the rules governing LS conversion are not well understood. In part, this is because the conversion process is mechanistically very different from classic LS transfer of standing phases; challenges also arise due to the need to characterize structure in noncovalently adsorbed ligand layers <0.5 nm thick, at scales ranging from millimeters to nanometers. Here, we show that scanning electron microscopy enables diynoic acid lying-down phases to be imaged across this range of scales; using this structural information, we establish conditions for LS conversion to create hierarchical microscopic and nanoscopic functional patterns. Such control opens the door to tailoring noncovalent surface chemistry of 2D materials to pattern local interactions with the environment.

Translocation of the Catalytic Domain of Diphtheria Toxin across Planar Phospholipid Bilayers by Its Own T Domain

NASA Astrophysics Data System (ADS)

Oh, Kyoung Joon; Senzel, Lisa; Collier, R. John; Finkelstein, Alan

1999-07-01

The T domain of diphtheria toxin is known to participate in the pH-dependent translocation of the catalytic C domain of the toxin across the endosomal membrane, but how it does so, and whether cellular proteins are also required for this process, remain unknown. Here, we report results showing that the T domain alone is capable of translocating the entire C domain across model, planar phospholipid bilayers in the absence of other proteins. The T domain therefore contains the entire molecular machinery for mediating transfer of the catalytic domain of diphtheria toxin across membranes.

Crosslinguistic Transfer in the Acquisition of Compound Words in Persian-English Bilinguals

ERIC Educational Resources Information Center

Foroodi-Nejad, Farzaneh; Paradis, Johanne

2009-01-01

Crosslinguistic transfer in bilingual language acquisition has been widely reported in various linguistic domains (e.g., Dopke, 1998; Nicoladis, 1999; Paradis, 2001). In this study we examined structural overlap (Dopke, 2000; Muller and Hulk, 2001) and dominance (Yip and Matthews, 2000) as explanatory factors for crosslinguistic transfer in…

Large-Scale Studies on the Transferability of General Problem-Solving Skills and the Pedagogic Potential of Physics

ERIC Educational Resources Information Center

Mashood, K. K.; Singh, Vijay A.

2013-01-01

Research suggests that problem-solving skills are transferable across domains. This claim, however, needs further empirical substantiation. We suggest correlation studies as a methodology for making preliminary inferences about transfer. The correlation of the physics performance of students with their performance in chemistry and mathematics in…

Cross-domain expression recognition based on sparse coding and transfer learning

NASA Astrophysics Data System (ADS)

Yang, Yong; Zhang, Weiyi; Huang, Yong

2017-05-01

Traditional facial expression recognition methods usually assume that the training set and the test set are independent and identically distributed. However, in actual expression recognition applications, the conditions of independent and identical distribution are hardly satisfied for the training set and test set because of the difference of light, shade, race and so on. In order to solve this problem and improve the performance of expression recognition in the actual applications, a novel method based on transfer learning and sparse coding is applied to facial expression recognition. First of all, a common primitive model, that is, the dictionary is learnt. Then, based on the idea of transfer learning, the learned primitive pattern is transferred to facial expression and the corresponding feature representation is obtained by sparse coding. The experimental results in CK +, JAFFE and NVIE database shows that the transfer learning based on sparse coding method can effectively improve the expression recognition rate in the cross-domain expression recognition task and is suitable for the practical facial expression recognition applications.

The Role of FRET in Non-Fullerene Organic Solar Cells: Implications for Molecular Design.

PubMed

Gautam, Bhoj R; Younts, Robert; Carpenter, Joshua; Ade, Harald; Gundogdu, Kenan

2018-04-19

Non-fullerene acceptors (NFAs) have been demonstrated to be promising candidates for highly efficient organic photovoltaic (OPV) devices. The tunability of absorption characteristics of NFAs can be used to make OPVs with complementary donor-acceptor absorption to cover a broad range of the solar spectrum. However, both charge transfer from donor to acceptor moieties and energy (energy) transfer from high-bandgap to low-bandgap materials are possible in such structures. Here, we show that when charge transfer and exciton transfer processes are both present, the coexistence of excitons in both domains can cause a loss mechanism. Charge separation of excitons in a low-bandgap material is hindered due to exciton population in the larger bandgap acceptor domains. Our results further show that excitons in low-bandgap material should have a relatively long lifetime compared to the transfer time of excitons from higher bandgap material in order to contribute to the charge separation. These observations provide significant guidance for design and development of new materials in OPV applications.

The three lives of viral fusion peptides

PubMed Central

Apellániz, Beatriz; Huarte, Nerea; Largo, Eneko; Nieva, José L.

2014-01-01

Fusion peptides comprise conserved hydrophobic domains absolutely required for the fusogenic activity of glycoproteins from divergent virus families. After 30 years of intensive research efforts, the structures and functions underlying their high degree of sequence conservation are not fully elucidated. The long-hydrophobic viral fusion peptide (VFP) sequences are structurally constrained to access three successive states after biogenesis. Firstly, the VFP sequence must fulfill the set of native interactions required for (meta) stable folding within the globular ectodomains of glycoprotein complexes. Secondly, at the onset of the fusion process, they get transferred into the target cell membrane and adopt specific conformations therein. According to commonly accepted mechanistic models, membrane-bound states of the VFP might promote the lipid bilayer remodeling required for virus-cell membrane merger. Finally, at least in some instances, several VFPs co-assemble with transmembrane anchors into membrane integral helical bundles, following a locking movement hypothetically coupled to fusion-pore expansion. Here we review different aspects of the three major states of the VFPs, including the functional assistance by other membrane-transferring glycoprotein regions, and discuss briefly their potential as targets for clinical intervention. PMID:24704587

Convergence of Distributed Optimal Controls on the Internal Energy in Mixed Elliptic Problems when the Heat Transfer Coefficient Goes to Infinity

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

Gariboldi, C.; E-mail: cgariboldi@exa.unrc.edu.ar; Tarzia, D.

2003-05-21

We consider a steady-state heat conduction problem P{sub {alpha}} with mixed boundary conditions for the Poisson equation depending on a positive parameter {alpha} , which represents the heat transfer coefficient on a portion {gamma} {sub 1} of the boundary of a given bounded domain in R{sup n} . We formulate distributed optimal control problems over the internal energy g for each {alpha}. We prove that the optimal control g{sub o}p{sub {alpha}} and its corresponding system u{sub go}p{sub {alpha}}{sub {alpha}} and adjoint p{sub go}p{sub {alpha}}{sub {alpha}} states for each {alpha} are strongly convergent to g{sub op},u{sub gop} and p{sub gop} ,more » respectively, in adequate functional spaces. We also prove that these limit functions are respectively the optimal control, and the system and adjoint states corresponding to another distributed optimal control problem for the same Poisson equation with a different boundary condition on the portion {gamma}{sub 1} . We use the fixed point and elliptic variational inequality theories.« less

Lipid Regulated Intramolecular Conformational Dynamics of SNARE-Protein Ykt6

NASA Astrophysics Data System (ADS)

Dai, Yawei; Seeger, Markus; Weng, Jingwei; Song, Song; Wang, Wenning; Tan, Yan-Wen

2016-08-01

Cellular informational and metabolic processes are propagated with specific membrane fusions governed by soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNARE). SNARE protein Ykt6 is highly expressed in brain neurons and plays a critical role in the membrane-trafficking process. Studies suggested that Ykt6 undergoes a conformational change at the interface between its longin domain and the SNARE core. In this work, we study the conformational state distributions and dynamics of rat Ykt6 by means of single-molecule Förster Resonance Energy Transfer (smFRET) and Fluorescence Cross-Correlation Spectroscopy (FCCS). We observed that intramolecular conformational dynamics between longin domain and SNARE core occurred at the timescale ~200 μs. Furthermore, this dynamics can be regulated and even eliminated by the presence of lipid dodecylphoshpocholine (DPC). Our molecular dynamic (MD) simulations have shown that, the SNARE core exhibits a flexible structure while the longin domain retains relatively stable in apo state. Combining single molecule experiments and theoretical MD simulations, we are the first to provide a quantitative dynamics of Ykt6 and explain the functional conformational change from a qualitative point of view.

Modulated electron-multiplied fluorescence lifetime imaging microscope: all-solid-state camera for fluorescence lifetime imaging.

PubMed

Zhao, Qiaole; Schelen, Ben; Schouten, Raymond; van den Oever, Rein; Leenen, René; van Kuijk, Harry; Peters, Inge; Polderdijk, Frank; Bosiers, Jan; Raspe, Marcel; Jalink, Kees; Geert Sander de Jong, Jan; van Geest, Bert; Stoop, Karel; Young, Ian Ted

2012-12-01

We have built an all-solid-state camera that is directly modulated at the pixel level for frequency-domain fluorescence lifetime imaging microscopy (FLIM) measurements. This novel camera eliminates the need for an image intensifier through the use of an application-specific charge coupled device design in a frequency-domain FLIM system. The first stage of evaluation for the camera has been carried out. Camera characteristics such as noise distribution, dark current influence, camera gain, sampling density, sensitivity, linearity of photometric response, and optical transfer function have been studied through experiments. We are able to do lifetime measurement using our modulated, electron-multiplied fluorescence lifetime imaging microscope (MEM-FLIM) camera for various objects, e.g., fluorescein solution, fixed green fluorescent protein (GFP) cells, and GFP-actin stained live cells. A detailed comparison of a conventional microchannel plate (MCP)-based FLIM system and the MEM-FLIM system is presented. The MEM-FLIM camera shows higher resolution and a better image quality. The MEM-FLIM camera provides a new opportunity for performing frequency-domain FLIM.

[Aging explosive detection using terahertz time-domain spectroscopy].

PubMed

Meng, Kun; Li, Ze-ren; Liu, Qiao

2011-05-01

Detecting the aging situation of stock explosive is essentially meaningful to the research on the capability, security and stability of explosive. Existing aging explosive detection techniques, such as scan microscope technique, Fourier transfer infrared spectrum technique, gas chromatogram mass spectrum technique and so on, are either not able to differentiate whether the explosive is aging or not, or not able to image the structure change of the molecule. In the present paper, using the density functional theory (DFT), the absorb spectrum changes after the explosive aging were calculated, from which we can clearly find the difference of spectrum between explosive molecule and aging ones in the terahertz band. The terahertz time-domain spectrum (THz-TDS) system as well as its frequency spectrum resolution and measured range are analyzed. Combined with the existing experimental results and the essential characters of the terahertz wave, the application of THz-TDS technique to the detection of aging explosive was demonstrated from the aspects of feasibility, veracity and practicability. On the base of that, the authors advance the new method of aging explosive detection using the terahertz time-domain spectrum technique.

Allan deviation computations of a linear frequency synthesizer system using frequency domain techniques

NASA Technical Reports Server (NTRS)

Wu, Andy

1995-01-01

Allan Deviation computations of linear frequency synthesizer systems have been reported previously using real-time simulations. Even though it takes less time compared with the actual measurement, it is still very time consuming to compute the Allan Deviation for long sample times with the desired confidence level. Also noises, such as flicker phase noise and flicker frequency noise, can not be simulated precisely. The use of frequency domain techniques can overcome these drawbacks. In this paper the system error model of a fictitious linear frequency synthesizer is developed and its performance using a Cesium (Cs) atomic frequency standard (AFS) as a reference is evaluated using frequency domain techniques. For a linear timing system, the power spectral density at the system output can be computed with known system transfer functions and known power spectral densities from the input noise sources. The resulting power spectral density can then be used to compute the Allan Variance at the system output. Sensitivities of the Allan Variance at the system output to each of its independent input noises are obtained, and they are valuable for design trade-off and trouble-shooting.

Impedance based time-domain modeling of lithium-ion batteries: Part I

NASA Astrophysics Data System (ADS)

Gantenbein, Sophia; Weiss, Michael; Ivers-Tiffée, Ellen

2018-03-01

This paper presents a novel lithium-ion cell model, which simulates the current voltage characteristic as a function of state of charge (0%-100%) and temperature (0-30 °C). It predicts the cell voltage at each operating point by calculating the total overvoltage from the individual contributions of (i) the ohmic loss η0, (ii) the charge transfer loss of the cathode ηCT,C, (iii) the charge transfer loss and the solid electrolyte interface loss of the anode ηSEI/CT,A, and (iv) the solid state and electrolyte diffusion loss ηDiff,A/C/E. This approach is based on a physically meaningful equivalent circuit model, which is parametrized by electrochemical impedance spectroscopy and time domain measurements, covering a wide frequency range from MHz to μHz. The model is exemplarily parametrized to a commercial, high-power 350 mAh graphite/LiNiCoAlO2-LiCoO2 pouch cell and validated by continuous discharge and charge curves at varying temperature. For the first time, the physical background of the model allows the operator to draw conclusions about the performance-limiting factor at various operating conditions. Not only can the model help to choose application-optimized cell characteristics, but it can also support the battery management system when taking corrective actions during operation.

Quantum Computational Studies of Electron Transfer in Respiratory Complex III and its Application for Designing New Mitocan Drugs

NASA Astrophysics Data System (ADS)

Hagras, Muhammad Ahmed

Electron transfer occurs in many biological systems which are imperative to sustain life; oxidative phosphorylation in prokaryotes and eukaryotes, and photophosphorylation in photosynthetic and plant cells are well-balanced and complementary processes. Investigating electron transfer in those natural systems provides detailed knowledge of the atomistic events that lead eventually to production of ATP, or harvesting light energy. Ubiquinol:cytochrome c oxidoreductase complex (also known as bc 1 complex, or respiratory complex III) is a middle player in the electron transport proton pumping orchestra, located in the inner-mitochondrial membrane in eukaryotes or plasma membrane in prokaryotes, which converts the free energy of redox reactions to electrochemical proton gradient across the membrane, following the fundamental chemiosmotic principle discovered by Peter Mitchell 1. In humans, the malfunctioned bc1 complex plays a major role in many neurodegenerative diseases, stress-induced aging, and cancer development, because it produces most of the reactive oxygen species, which are also involved in cellular signaling 2. The mitochondrial bc1 complex has an intertwined dimeric structure comprised of 11 subunits in each monomer, but only three of them have catalytic function, and those are the only domains found in bacterial bc1 complex. The core subunits include: Rieske domain, which incorporates iron-sulfur cluster [2Fe-2S]; trans-membrane cytochrome b domain, incorporating low-potential heme group (heme b L) and high-potential heme group (heme b H); and cytochrome c1 domain, containing heme c1 group and two separate binding sites, Qo (or QP) site where the hydrophobic electron carrier ubihydroquinol QH2 is oxidized, and Qi (or QN) site where ubiquinone molecule Q is reduced 3. Electrons and protons in the bc1 complex flow according to the proton-motive Q-cycle proposed by Mitchell, which includes a unique electron flow bifurcation at the Qo site. At this site, one electron of a bound QH2 molecule transfers to [2Fe-2S] cluster of the Rieske domain, docked at the proximal docking site, and another electron transfers to heme b L , which subsequently passes it to heme bH , and finally to Q or SQ molecule bound at the Qi-site 4. Rieske domain undergoes a domain movement 22 A to bind at the distal docking site, where [2Fe-2S] cluster passes its electron to heme c1, which in turn passes it to heme c of the water-soluble cytochrome c carrier 3c, 5 (which shuttles it to cytochrome c oxidase, complex IV). In the current compiled work presented in the subsequent chapters, we deployed a stacking tiers hierarchy where each chapter's work presents a foundation for the next one. In chapter 1, we first present different methods to calculate tunneling currents in proteins including a new derivation method for the inter-atomic tunneling current method. In addition, we show the results of the inter-atomic tunneling current theory on models based on heme bL-heme bH redox pair system in bc1 complex. Afterwards, in chapter 2, we examine the electron tunneling pathways 6 between different intra-monomeric and inter-monomeric redox centers of bc1 complex, including its electron carriers - ubiquinol, ubiquinone, and cytochrome c molecules, using the well-studied coarse-grained interatomic method of the tunneling current theory 7. Going through the different tunneling pathways in bc1 complex, we discovered a pair of internal switches that modulate the electron transfer rate which we discuss in full details in chapter 3. Motivated by the discovery of those internal switches, we discuss in chapter 4 the discovery of a new binding pocket (designated as NonQ-site or NQ-site for short) in bc 1 complex which is located at the opposite side of the enzyme with respect to Qo site. In contrast to Qo site, however, the NQ-site penetrates deeply in the cytochrome b domain and reaches very closely the LH region. Hence the NQ-site provides a suitable binding pocket for ligands that can influence the orientation of Phe90 residue, and hence modulate the corresponding ET rate between heme b L and heme bH. Finally we present in chapter 5 our unique integrated software package (called Electron Tunneling in Proteins Program or ETP) which provides an environment with different capabilities such as tunneling current calculation, semi-empirical quantum mechanical calculation and molecular modeling simulation for calculation and analysis of electron transfer reactions in proteins.

A two-domain protein triggers heat shock pathway and necrosis pathway both in model plant and nematode.

PubMed

Ruan, Lifang; Wang, Huihui; Cai, Ge; Peng, Donghai; Zhou, Hua; Zheng, Jinshui; Zhu, Lei; Wang, Xixi; Yu, Haoquan; Li, Seng; Geng, Ce; Sun, Ming

2015-11-01

The entomopathogen Bacillus thuringiensis is equipped with multiple virulent factors. The genome sequence of B. thuringiensis YBT1520 revealed the presence of a two-domain protein named Nel which is composed of a necrosis-inducing phytophthora protein 1-like domain found in phytopathogens and a ricin B-like lectin domain. The merging of two distantly related domains is relatively rare. Nel induced necrosis and pathogen-triggered immunity (PTI) on model plants. The Nel also exhibited inhibition activity to nematode. Microscopic observation showed that the toxicity of Nel to nematodes targets the intestine. Quantitative proteomics revealed that Nel stimulated the host defence. The Nel thus possesses dual roles, as both toxin and elicitor. Remarkably, the Nel protein triggered a similar response, induction of the heat shock pathway and the necrosis pathway, in both model plants and nematodes. The unusual ability of Nel to function across kingdom suggests a highly conserved mechanism in eukaryotes that predates the divergence of plants and animal. It is also speculated that the two-domain protein is the result of horizontal gene transfer (HGT) between phytopathogens and entomopathogens. Our results provide an example that HGT occurs between members of different species or even genera with lower frequency are particularly important for evolution of new bacterial pathogen lineages with new virulence. Bacillus thuringiensis occupies the same ecological niches, plant and soil, as phytopathogens, providing the opportunity for gene exchange. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

A Novel Mechanism of Latency in Matrix Metalloproteinases*

PubMed Central

López-Pelegrín, Mar; Ksiazek, Miroslaw; Karim, Abdulkarim Y.; Guevara, Tibisay; Arolas, Joan L.; Potempa, Jan; Gomis-Rüth, F. Xavier

2015-01-01

The matrix metalloproteinases (MMPs) are a family of secreted soluble or membrane-anchored multimodular peptidases regularly found in several paralogous copies in animals and plants, where they have multiple functions. The minimal consensus domain architecture comprises a signal peptide, a 60–90-residue globular prodomain with a conserved sequence motif including a cysteine engaged in “cysteine-switch” or “Velcro” mediated latency, and a catalytic domain. Karilysin, from the human periodontopathogen Tannerella forsythia, is the only bacterial MMP to have been characterized biochemically to date. It shares with eukaryotic forms the catalytic domain but none of the flanking domains. Instead of the consensus MMP prodomain, it features a 14-residue propeptide, the shortest reported for a metallopeptidase, which lacks cysteines. Here we determined the structure of a prokarilysin fragment encompassing the propeptide and the catalytic domain, and found that the former runs across the cleft in the opposite direction to a bound substrate and inhibits the latter through an “aspartate-switch” mechanism. This finding is reminiscent of latency maintenance in the otherwise unrelated astacin and fragilysin metallopeptidase families. In addition, in vivo and biochemical assays showed that the propeptide contributes to protein folding and stability. Our analysis of prokarilysin reveals a novel mechanism of latency and activation in MMPs. Finally, our findings support the view that the karilysin catalytic domain was co-opted by competent bacteria through horizontal gene transfer from a eukaryotic source, and later evolved in a specific bacterial environment. PMID:25555916

Object recognition using deep convolutional neural networks with complete transfer and partial frozen layers

NASA Astrophysics Data System (ADS)

Kruithof, Maarten C.; Bouma, Henri; Fischer, Noëlle M.; Schutte, Klamer

2016-10-01

Object recognition is important to understand the content of video and allow flexible querying in a large number of cameras, especially for security applications. Recent benchmarks show that deep convolutional neural networks are excellent approaches for object recognition. This paper describes an approach of domain transfer, where features learned from a large annotated dataset are transferred to a target domain where less annotated examples are available as is typical for the security and defense domain. Many of these networks trained on natural images appear to learn features similar to Gabor filters and color blobs in the first layer. These first-layer features appear to be generic for many datasets and tasks while the last layer is specific. In this paper, we study the effect of copying all layers and fine-tuning a variable number. We performed an experiment with a Caffe-based network on 1000 ImageNet classes that are randomly divided in two equal subgroups for the transfer from one to the other. We copy all layers and vary the number of layers that is fine-tuned and the size of the target dataset. We performed additional experiments with the Keras platform on CIFAR-10 dataset to validate general applicability. We show with both platforms and both datasets that the accuracy on the target dataset improves when more target data is used. When the target dataset is large, it is beneficial to freeze only a few layers. For a large target dataset, the network without transfer learning performs better than the transfer network, especially if many layers are frozen. When the target dataset is small, it is beneficial to transfer (and freeze) many layers. For a small target dataset, the transfer network boosts generalization and it performs much better than the network without transfer learning. Learning time can be reduced by freezing many layers in a network.

Dual Function of Phosphoubiquitin in E3 Activation of Parkin*

PubMed Central

Walinda, Erik; Morimoto, Daichi; Sugase, Kenji; Shirakawa, Masahiro

2016-01-01

Mutations in the gene encoding parkin, an auto-inhibited E3 ubiquitin ligase that functions in the clearance of damaged mitochondria, are the most common cause of autosomal recessive juvenile Parkinsonism. The mechanism regulating parkin activation remains poorly understood. Here we show, by using isothermal titration calorimetry, solution NMR, and fluorescence spectroscopy, that parkin can bind ubiquitin and phosphomimetic ubiquitin by recognizing the canonical hydrophobic patch and C terminus of ubiquitin. The affinity of parkin for both phosphomimetic and unmodified ubiquitin is markedly enhanced upon removal of the ubiquitin-like (UBL) domain of parkin. This suggests that the agonistic binding of ubiquitin to parkin in trans is counterbalanced by the antagonistic activity of the parkin UBL domain in cis. Intriguingly, UBL binding is enthalpy-driven, whereas ubiquitin binding is driven by an increase in the total entropy of the system. These thermodynamic differences are explained by different chemistry in the ubiquitin- and UBL-binding pockets of parkin and, as shown by molecular dynamics simulations, are not a consequence of changes in protein conformational entropy. Indeed, comparison of conformational fluctuations reveals that the RING1-IBR element becomes considerably more rigid upon complex formation. A model of parkin activation is proposed in which E2∼Ub binding triggers large scale diffusional motion of the RING2 domain toward the ubiquitin-stabilized RING1-IBR assembly to complete formation of the active parkin-E2∼Ub transfer complex. Thus, ubiquitin plays a dual role in parkin activation by competing with the inhibitory UBL domain and stabilizing the active form of parkin. PMID:27284007

Crystal Structure and Oligomeric State of the RetS Signaling Kinase Sensory Domain

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

Jing, X.; Jaw, J; Robinson, H

2010-01-01

The opportunistic pathogen Pseudomonas aeruginosa may cause both acute and chronic-persistent infections in predisposed individuals. Acute infections require the presence of a functional type III secretion system (T3SS), whereas chronic P. aeruginosa infections are characterized by the formation of drug-resistant biofilms. The T3SS and biofilm formation are reciprocally regulated by the signaling kinases LadS, RetS, and GacS. RetS downregulates biofilm formation and upregulates expression of the T3SS through a unique mechanism. RetS forms a heterodimeric complex with GacS and thus prevents GacS autophosphorylation and downstream signaling. The signals that regulate RetS are not known but RetS possesses a distinctive periplasmicmore » sensor domain that is believed to serve as receptor for the regulatory ligand. We have determined the crystal structure of the RetS sensory domain at 2.0 {angstrom} resolution. The structure closely resembles those of carbohydrate binding modules of other proteins, suggesting that the elusive ligands are likely carbohydrate moieties. In addition to the conserved beta-sandwich structure, the sensory domain features two alpha helices which create a unique surface topology. Protein-protein crosslinking and fluorescence energy transfer experiments also revealed that the sensory domain dimerizes with a dissociation constant of K{sub d} = 580 {+-} 50 nM, a result with interesting implications for our understanding of the underlying signaling mechanism.« less

Fully unsteady subsonic and supersonic potential aerodynamics for complex aircraft configurations with applications to flutter

NASA Technical Reports Server (NTRS)

Tseng, K.; Morino, L.

1975-01-01

A general formulation is presented for the analysis of steady and unsteady, subsonic and supersonic aerodynamics for complex aircraft configurations. The theoretical formulation, the numerical procedure, the description of the program SOUSSA (steady, oscillatory and unsteady, subsonic and supersonic aerodynamics) and numerical results are included. In particular, generalized forces for fully unsteady (complex frequency) aerodynamics for a wing-body configuration, AGARD wing-tail interference in both subsonic and supersonic flows as well as flutter analysis results are included. The theoretical formulation is based upon an integral equation, which includes completely arbitrary motion. Steady and oscillatory aerodynamic flows are considered. Here small-amplitude, fully transient response in the time domain is considered. This yields the aerodynamic transfer function (Laplace transform of the fully unsteady operator) for frequency domain analysis. This is particularly convenient for the linear systems analysis of the whole aircraft.

Structural mechanism of voltage-dependent gating in an isolated voltage-sensing domain.

PubMed

Li, Qufei; Wanderling, Sherry; Paduch, Marcin; Medovoy, David; Singharoy, Abhishek; McGreevy, Ryan; Villalba-Galea, Carlos A; Hulse, Raymond E; Roux, Benoît; Schulten, Klaus; Kossiakoff, Anthony; Perozo, Eduardo

2014-03-01

The transduction of transmembrane electric fields into protein motion has an essential role in the generation and propagation of cellular signals. Voltage-sensing domains (VSDs) carry out these functions through reorientations of positive charges in the S4 helix. Here, we determined crystal structures of the Ciona intestinalis VSD (Ci-VSD) in putatively active and resting conformations. S4 undergoes an ~5-Å displacement along its main axis, accompanied by an ~60° rotation. This movement is stabilized by an exchange in countercharge partners in helices S1 and S3 that generates an estimated net charge transfer of ~1 eo. Gating charges move relative to a ''hydrophobic gasket' that electrically divides intra- and extracellular compartments. EPR spectroscopy confirms the limited nature of S4 movement in a membrane environment. These results provide an explicit mechanism for voltage sensing and set the basis for electromechanical coupling in voltage-dependent enzymes and ion channels.

There’s plenty of light at the bottom: statistics of photon penetration depth in random media

PubMed Central

Martelli, Fabrizio; Binzoni, Tiziano; Pifferi, Antonio; Spinelli, Lorenzo; Farina, Andrea; Torricelli, Alessandro

2016-01-01

We propose a comprehensive statistical approach describing the penetration depth of light in random media. The presented theory exploits the concept of probability density function f(z|ρ, t) for the maximum depth reached by the photons that are eventually re-emitted from the surface of the medium at distance ρ and time t. Analytical formulas for f, for the mean maximum depth 〈zmax〉 and for the mean average depth reached by the detected photons at the surface of a diffusive slab are derived within the framework of the diffusion approximation to the radiative transfer equation, both in the time domain and the continuous wave domain. Validation of the theory by means of comparisons with Monte Carlo simulations is also presented. The results are of interest for many research fields such as biomedical optics, advanced microscopy and disordered photonics. PMID:27256988

FRET measurements of kinesin neck orientation reveal a structural basis for processivity and asymmetry.

PubMed

Martin, Douglas S; Fathi, Reza; Mitchison, Timothy J; Gelles, Jeff

2010-03-23

As the smallest and simplest motor enzymes, kinesins have served as the prototype for understanding the relationship between protein structure and mechanochemical function of enzymes in this class. Conventional kinesin (kinesin-1) is a motor enzyme that transports cargo toward the plus end of microtubules by a processive, asymmetric hand-over-hand mechanism. The coiled-coil neck domain, which connects the two kinesin motor domains, contributes to kinesin processivity (the ability to take many steps in a row) and is proposed to be a key determinant of the asymmetry in the kinesin mechanism. While previous studies have defined the orientation and position of microtubule-bound kinesin motor domains, the disposition of the neck coiled-coil remains uncertain. We determined the neck coiled-coil orientation using a multidonor fluorescence resonance energy transfer (FRET) technique to measure distances between microtubules and bound kinesin molecules. Microtubules were labeled with a new fluorescent taxol donor, TAMRA-X-taxol, and kinesin derivatives with an acceptor fluorophore attached at positions on the motor and neck coiled-coil domains were used to reconstruct the positions and orientations of the domains. FRET measurements to positions on the motor domain were largely consistent with the domain orientation determined in previous studies, validating the technique. Measurements to positions on the neck coiled-coil were inconsistent with a radial orientation and instead demonstrated that the neck coiled-coil is parallel to the microtubule surface. The measured orientation provides a structural explanation for how neck surface residues enhance processivity and suggests a simple hypothesis for the origin of kinesin step asymmetry and "limping."

Probing membrane protein structure using water polarization transfer solid-state NMR.

PubMed

Williams, Jonathan K; Hong, Mei

2014-10-01

Water plays an essential role in the structure and function of proteins, lipid membranes and other biological macromolecules. Solid-state NMR heteronuclear-detected (1)H polarization transfer from water to biomolecules is a versatile approach for studying water-protein, water-membrane, and water-carbohydrate interactions in biology. We review radiofrequency pulse sequences for measuring water polarization transfer to biomolecules, the mechanisms of polarization transfer, and the application of this method to various biological systems. Three polarization transfer mechanisms, chemical exchange, spin diffusion and NOE, manifest themselves at different temperatures, magic-angle-spinning frequencies, and pulse irradiations. Chemical exchange is ubiquitous in all systems examined so far, and spin diffusion plays the key role in polarization transfer within the macromolecule. Tightly bound water molecules with long residence times are rare in proteins at ambient temperature. The water polarization-transfer technique has been used to study the hydration of microcrystalline proteins, lipid membranes, and plant cell wall polysaccharides, and to derive atomic-resolution details of the kinetics and mechanism of ion conduction in channels and pumps. Using this approach, we have measured the water polarization transfer to the transmembrane domain of the influenza M2 protein to obtain information on the structure of this tetrameric proton channel. At short mixing times, the polarization transfer rates are site-specific and depend on the pH, labile protons, sidechain conformation, as well as the radial position of the residues in this four-helix bundle. Despite the multiple dependences, the initial transfer rates reflect the periodic nature of the residue positions from the water-filled pore, thus this technique provides a way of gleaning secondary structure information, helix tilt angle, and the oligomeric structure of membrane proteins. Copyright © 2014 Elsevier Inc. All rights reserved.

On the detection of functionally coherent groups of protein domains with an extension to protein annotation

PubMed Central

McLaughlin, William A; Chen, Ken; Hou, Tingjun; Wang, Wei

2007-01-01

Background Protein domains coordinate to perform multifaceted cellular functions, and domain combinations serve as the functional building blocks of the cell. The available methods to identify functional domain combinations are limited in their scope, e.g. to the identification of combinations falling within individual proteins or within specific regions in a translated genome. Further effort is needed to identify groups of domains that span across two or more proteins and are linked by a cooperative function. Such functional domain combinations can be useful for protein annotation. Results Using a new computational method, we have identified 114 groups of domains, referred to as domain assembly units (DASSEM units), in the proteome of budding yeast Saccharomyces cerevisiae. The units participate in many important cellular processes such as transcription regulation, translation initiation, and mRNA splicing. Within the units the domains were found to function in a cooperative manner; and each domain contributed to a different aspect of the unit's overall function. The member domains of DASSEM units were found to be significantly enriched among proteins contained in transcription modules, defined as genes sharing similar expression profiles and presumably similar functions. The observation further confirmed the functional coherence of DASSEM units. The functional linkages of units were found in both functionally characterized and uncharacterized proteins, which enabled the assessment of protein function based on domain composition. Conclusion A new computational method was developed to identify groups of domains that are linked by a common function in the proteome of Saccharomyces cerevisiae. These groups can either lie within individual proteins or span across different proteins. We propose that the functional linkages among the domains within the DASSEM units can be used as a non-homology based tool to annotate uncharacterized proteins. PMID:17937820

Exercise training augments the dynamic heart rate response to vagal but not sympathetic stimulation in rats.

PubMed

Mizuno, Masaki; Kawada, Toru; Kamiya, Atsunori; Miyamoto, Tadayoshi; Shimizu, Shuji; Shishido, Toshiaki; Smith, Scott A; Sugimachi, Masaru

2011-04-01

We examined the transfer function of autonomic heart rate (HR) control in anesthetized sedentary and exercise-trained (16 wk, treadmill for 1 h, 5 times/wk at 15 m/min and 15-degree grade) rats for comparison to HR variability assessed in the conscious resting state. The transfer function from sympathetic stimulation to HR response was similar between groups (gain, 4.2 ± 1.5 vs. 4.5 ± 1.5 beats·min(-1)·Hz(-1); natural frequency, 0.07 ± 0.01 vs. 0.08 ± 0.01 Hz; damping coefficient, 1.96 ± 0.55 vs. 1.69 ± 0.15; and lag time, 0.7 ± 0.1 vs. 0.6 ± 0.1 s; sedentary vs. exercise trained, respectively, means ± SD). The transfer gain from vagal stimulation to HR response was 6.1 ± 3.0 in the sedentary and 9.7 ± 5.1 beats·min(-1)·Hz(-1) in the exercise-trained group (P = 0.06). The corner frequency (0.11 ± 0.05 vs. 0.17 ± 0.09 Hz) and lag time (0.1 ± 0.1 vs. 0.2 ± 0.1 s) did not differ between groups. When the sympathetic transfer gain was averaged for very-low-frequency and low-frequency bands, no significant group effect was observed. In contrast, when the vagal transfer gain was averaged for very-low-frequency, low-frequency, and high-frequency bands, exercise training produced a significant group effect (P < 0.05 by two-way, repeated-measures ANOVA). These findings suggest that, in the frequency domain, exercise training augments the dynamic HR response to vagal stimulation but not sympathetic stimulation, regardless of the frequency bands.

Characterization and Upscaling of Pore Scale Hydrodynamic Mass Transfer

NASA Astrophysics Data System (ADS)

Gouze, P.; Roubinet, D.; Dentz, M.; Planes, V.; Russian, A.

2017-12-01

Imaging reservoir rocks in 3D using X-ray microtomography with spatial resolution ranging from about 1 to 10 mm provides us a unique opportunity not only to characterize pore space geometry but also for simulating hydrodynamical processes. Yet, pores and throats displaying sizes smaller than the resolution cannot be distinguished on the images and must be assigned to a so called microporous phase during the process of image segmentation. Accordingly one simulated mass transfers caused by advection and diffusion in the connected pores (mobile domain) and diffusion in the microporous clusters (immobile domain) using Time Domain Random Walk (TDRW) and developed a set of metrics that can be used to monitor the different mechanisms of transport in the sample, the final objective being of proposing a simple but accurate upscaled 1D model in which the particle travel times in the mobile and immobile domain and the number of mobile-immobile transfer events (called trapping events) are independently distributed random variables characterized by PDFs. For TDRW the solute concentration is represented by the density distribution of non-interacting point-like solute particles which move due to advection and dispersion. The set of metrics derives from different spatial and temporal statistical analyses of the particle motion, and is used for characterizing the particles transport (i) in the mobile domain in relation with the velocity field properties, (ii) in the immobile domain in relation with the structure and the properties of microporous phase and at the mobile-immobile interface. We specifically focused on how to model the trapping frequency and rate into the immobile domain in relation with the structure and the spatial distribution of the mobile-immobile domain interface. This thorough analysis of the particle motion for both simple artificial structures and real rock images allowed us to derive the parametrization of the upscaled 1D model.

Trends in survival and early functional outcomes from hospitalized severe adult traumatic brain injuries, Pennsylvania, 1998–2007

PubMed Central

Sánchez, Álvaro I; Krafty, Robert T; Weiss, Harold B; Rubiano, Andrés M; Peitzman, Andrew B; Puyana, Juan Carlos

2011-01-01

Objective To determine trends for in-hospital survival and functional outcomes at acute care hospital discharge for severe adult traumatic brain injury (SATBI) patients in Pennsylvania, during 1998–2007. Methods Secondary analysis of the Pennsylvania trauma outcome study database. Main Outcome Measures Survival and functional status scores of five domains (feeding, locomotion, expression, transfer mobility, and social interaction) fitted into logistic regression models adjusted for age, sex, race, co-morbidities, injury mechanism, extra-cranial injuries, severity scores, hospital stay, trauma center, and hospital level. Sensitivity analyses for functional outcomes were performed. Results There were 26,234 SATBI patients. Annual numbers of SATBI increased from 1,757 to 3,808 during 1998–2007. Falls accounted for 47.7% of all SATBI. Survival increased significantly from 72.5% to 82.7% (OR 1.10, 95%CI 1.08–1.11, P<0.001). In sensitivity analyses, trends of complete independence in functional outcomes increased significantly for expression (OR 1.01, 95%CI 1.00–1.02, P=0.011) and social interaction (OR 1.01, 95%CI 1.00–1.03, P=0.002). There were no significant variations over time for feeding, locomotion, and transfer mobility. Conclusions Trends for SATBI served by Pennsylvania’s established trauma system showed increases in rates but substantial reductions in mortality and significant improvements in functional outcomes at discharge for expression and social interaction. PMID:21386713

Structure and Regulatory Interactions of the Cytoplasmic Terminal Domains of Serotonin Transporter

PubMed Central

2014-01-01

Uptake of neurotransmitters by sodium-coupled monoamine transporters of the NSS family is required for termination of synaptic transmission. Transport is tightly regulated by protein–protein interactions involving the small cytoplasmic segments at the amino- and carboxy-terminal ends of the transporter. Although structures of homologues provide information about the transmembrane regions of these transporters, the structural arrangement of the terminal domains remains largely unknown. Here, we combined molecular modeling, biochemical, and biophysical approaches in an iterative manner to investigate the structure of the 82-residue N-terminal and 30-residue C-terminal domains of human serotonin transporter (SERT). Several secondary structures were predicted in these domains, and structural models were built using the Rosetta fragment-based methodology. One-dimensional 1H nuclear magnetic resonance and circular dichroism spectroscopy supported the presence of helical elements in the isolated SERT N-terminal domain. Moreover, introducing helix-breaking residues within those elements altered the fluorescence resonance energy transfer signal between terminal cyan fluorescent protein and yellow fluorescent protein tags attached to full-length SERT, consistent with the notion that the fold of the terminal domains is relatively well-defined. Full-length models of SERT that are consistent with these and published experimental data were generated. The resultant models predict confined loci for the terminal domains and predict that they move apart during the transport-related conformational cycle, as predicted by structures of homologues and by the “rocking bundle” hypothesis, which is consistent with spectroscopic measurements. The models also suggest the nature of binding to regulatory interaction partners. This study provides a structural context for functional and regulatory mechanisms involving SERT terminal domains. PMID:25093911

Functional analysis of recombinant human and Yarrowia lipolytica O-GlcNAc transferases expressed in Saccharomyces cerevisiae.

PubMed

Oh, Hye Ji; Moon, Hye Yun; Cheon, Seon Ah; Hahn, Yoonsoo; Kang, Hyun Ah

2016-10-01

O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is an important post-translational modification in many cellular processes. It is mediated by O-GlcNAc transferases (OGTs), which catalyze the addition of O-GlcNAc to serine or threonine residues of the target proteins. In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. Immunoblotting assays using antibody against O-GlcNAc revealed that recombinant hOGT (rhOGT), but not the recombinant YlOGT (rYlOGT), undergoes auto-O-GlcNAcylation in the heterologous host S. cerevisiae. Moreover, the rhOGT expressed in S. cerevisiae showed a catalytic activity during in vitro assays using casein kinase II substrates, whereas no such activity was obtained in rYlOGT. However, the chimeric human-Y. lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. Although the overexpression of full-length OGTs inhibited the growth of S. cerevisiae, no such inhibition was obtained upon overexpression of only the CTD fragment, indicating the role of TPR domain in growth inhibition. This is the first report on the functional analysis of the fungal OGT, indicating that the Y. lipolytica OGT retains its catalytic activity, although the physiological role and substrates of YlOGT remain to be elucidated.

Transfer of Expertise: An Eye Tracking and Think Aloud Study Using Dynamic Medical Visualizations

ERIC Educational Resources Information Center

Gegenfurtner, Andreas; Seppanen, Marko

2013-01-01

Expertise research has produced mixed results regarding the problem of transfer of expertise. Is expert performance context-bound or can the underlying processes be applied to more general situations? The present study tests whether expert performance and its underlying processes transfer to novel tasks within a domain. A mixed method study using…

Investigating Cognitive Transfer within the Framework of Music Practice: Genetic Pleiotropy Rather than Causality

ERIC Educational Resources Information Center

Mosing, Miriam A.; Madison, Guy; Pedersen, Nancy L.; Ullén, Fredrik

2016-01-01

The idea of far transfer effects in the cognitive sciences has received much attention in recent years. One domain where far transfer effects have frequently been reported is music education, with the prevailing idea that music practice entails an increase in cognitive ability (IQ). While cross-sectional studies consistently find significant…

Nanoscale control of stripe-ordered magnetic domain walls by vertical spin transfer torque in La0.67Sr0.33MnO3 film

NASA Astrophysics Data System (ADS)

Wang, Jing; Wu, Shizhe; Ma, Ji; Xie, Lishan; Wang, Chuanshou; Malik, Iftikhar Ahmed; Zhang, Yuelin; Xia, Ke; Nan, Ce-Wen; Zhang, Jinxing

2018-02-01

Stripe-ordered domains with perpendicular magnetic anisotropy have been intensively investigated due to their potential applications in high-density magnetic data-storage devices. However, the conventional control methods (e.g., epitaxial strain, local heating, magnetic field, and magnetoelectric effect) of the stripe-ordered domain walls either cannot meet the demands for miniaturization and low power consumption of spintronic devices or require high strength of the electric field due to the small value of the magnetoelectric effect at room temperature. Here, a domain-wall resistive effect of 0.1% was clarified in La0.67Sr0.33MnO3 thin films between the configurations of current in the plane and perpendicular to the plane of walls. Furthermore, a reversible nanoscale control of the domain-wall re-orientation by vertical spin transfer torque across the probe/film interface was achieved, where a probe voltage of 0.1 V was applied on a manganite-based capacitor. We also demonstrated that the stripe-ordered magnetic domain-wall re-orientation strongly depends on the AC frequency of the scanning probe voltage which was applied on the capacitor.

Magnonic band structure in a Co/Pd stripe domain system investigated by Brillouin light scattering and micromagnetic simulations

NASA Astrophysics Data System (ADS)

Banerjee, Chandrima; Gruszecki, Pawel; Klos, Jaroslaw W.; Hellwig, Olav; Krawczyk, Maciej; Barman, Anjan

2017-07-01

By combining Brillouin light scattering and micromagnetic simulations, we studied the spin-wave (SW) dynamics of a Co/Pd thin film multilayer, which features a stripe domain structure at remanence. The periodic up and down domains are separated by corkscrew type domain walls. The existence of these domains causes a scattering of the otherwise bulk and surface SW modes, which form mode families, similar to a one-dimensional magnonic crystal. The dispersion relation and mode profiles of SWs are measured for the transferred wave vector parallel and perpendicular to the domain axis.

Effect of wettability of a porous stainless steel on thermally induced liquid-vapor interface behavior

NASA Astrophysics Data System (ADS)

Oka, C.; Odagiri, K.; Nagano, H.

2017-12-01

Control of thermally induced liquid-vapor interface behavior at the contact surface of porous media is crucial for development of two-phase heat transfer devices such as loop heat pipes. The behavior experiences three modes with increase of heat flux, and the middle mode possesses the highest heat transfer performance. In this paper, the effect of improving wettability of the porous media is demonstrated experimentally and numerically for the first time, in particular with regard to the effect on a domain of the middle mode. Ethanol wettability of a porous stainless steel was improved via a facile method, which was a simple acid treatment. As a result, the domain of the middle mode was extended as a consequence of the wettability improvement. The mode transfers from the middle to the last one when the pressure drop in the liquid supply exceeds the capillary pressure of liquid bridges formed between the heating plate and the porous medium. Hence, the extension of the domain suggested that the capillary pressure was increased by the wettability improvement. This was verified via numerical calculation. The calculated capillary pressure was increased by 7% after improving wettability, which resulted in the extension of the domain of the middle mode.

RCT of working memory training in ADHD: long-term near-transfer effects.

PubMed

Hovik, Kjell Tore; Saunes, Brit-Kari; Aarlien, Anne Kristine; Egeland, Jens

2013-01-01

The aim of the study is to evaluate the long-term near-transfer effects of computerized working memory (WM) training on standard WM tasks in children with Attention-Deficit/Hyperactivity Disorder (ADHD). Sixty-seven children aged 10-12 years in Vestfold/Telemark counties (Norway) diagnosed with F90.0 Hyperkinetic disorder (ICD-10) were randomly assigned to training or control group. The training group participated in a 25-day training program at school, while the control group received treatment-as-usual. Participants were tested one week before intervention, immediately after and eight months later. Based on a component analysis, six measures of WM were grouped into composites representing Visual, Auditory and Manipulation WM. The training group had significant long-term differential gains compared to the control group on all outcome measures. Performance gains for the training group were significantly higher in the visual domain than in the auditory domain. The differential gain in Manipulation WM persisted after controlling for an increase in simple storage capacity. Systematic training resulted in a long-term positive gain in performance on similar tasks, indicating the viability of training interventions for children with ADHD. The results provide evidence for both domain-general and domain-specific models. Far-transfer effects were not investigated in this article. Controlled-Trials.com ISRCTN19133620.

Classify epithelium-stroma in histopathological images based on deep transferable network.

PubMed

Yu, X; Zheng, H; Liu, C; Huang, Y; Ding, X

2018-04-20

Recently, the deep learning methods have received more attention in histopathological image analysis. However, the traditional deep learning methods assume that training data and test data have the same distributions, which causes certain limitations in real-world histopathological applications. However, it is costly to recollect a large amount of labeled histology data to train a new neural network for each specified image acquisition procedure even for similar tasks. In this paper, an unsupervised domain adaptation is introduced into a typical deep convolutional neural network (CNN) model to mitigate the repeating of the labels. The unsupervised domain adaptation is implemented by adding two regularisation terms, namely the feature-based adaptation and entropy minimisation, to the object function of a widely used CNN model called the AlexNet. Three independent public epithelium-stroma datasets were used to verify the proposed method. The experimental results have demonstrated that in the epithelium-stroma classification, the proposed method can achieve better performance than the commonly used deep learning methods and some existing deep domain adaptation methods. Therefore, the proposed method can be considered as a better option for the real-world applications of histopathological image analysis because there is no requirement for recollection of large-scale labeled data for every specified domain. © 2018 The Authors Journal of Microscopy © 2018 Royal Microscopical Society.

Photonic band structures solved by a plane-wave-based transfer-matrix method.

PubMed

Li, Zhi-Yuan; Lin, Lan-Lan

2003-04-01

Transfer-matrix methods adopting a plane-wave basis have been routinely used to calculate the scattering of electromagnetic waves by general multilayer gratings and photonic crystal slabs. In this paper we show that this technique, when combined with Bloch's theorem, can be extended to solve the photonic band structure for 2D and 3D photonic crystal structures. Three different eigensolution schemes to solve the traditional band diagrams along high-symmetry lines in the first Brillouin zone of the crystal are discussed. Optimal rules for the Fourier expansion over the dielectric function and electromagnetic fields with discontinuities occurring at the boundary of different material domains have been employed to accelerate the convergence of numerical computation. Application of this method to an important class of 3D layer-by-layer photonic crystals reveals the superior convergency of this different approach over the conventional plane-wave expansion method.

Identification of the heat transfer coefficient in the two-dimensional model of binary alloy solidification

NASA Astrophysics Data System (ADS)

Hetmaniok, Edyta; Hristov, Jordan; Słota, Damian; Zielonka, Adam

2017-05-01

The paper presents the procedure for solving the inverse problem for the binary alloy solidification in a two-dimensional space. This is a continuation of some previous works of the authors investigating a similar problem but in the one-dimensional domain. Goal of the problem consists in identification of the heat transfer coefficient on boundary of the region and in reconstruction of the temperature distribution inside the considered region in case when the temperature measurements in selected points of the alloy are known. Mathematical model of the problem is based on the heat conduction equation with the substitute thermal capacity and with the liquidus and solidus temperatures varying in dependance on the concentration of the alloy component. For describing this concentration the Scheil model is used. Investigated procedure involves also the parallelized Ant Colony Optimization algorithm applied for minimizing a functional expressing the error of approximate solution.

State of the art in electromagnetic modeling for the Compact Linear Collider

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

Candel, Arno; Kabel, Andreas; Lee, Lie-Quan

SLAC's Advanced Computations Department (ACD) has developed the parallel 3D electromagnetic time-domain code T3P for simulations of wakefields and transients in complex accelerator structures. T3P is based on state-of-the-art Finite Element methods on unstructured grids and features unconditional stability, quadratic surface approximation and up to 6th-order vector basis functions for unprecedented simulation accuracy. Optimized for large-scale parallel processing on leadership supercomputing facilities, T3P allows simulations of realistic 3D structures with fast turn-around times, aiding the design of the next generation of accelerator facilities. Applications include simulations of the proposed two-beam accelerator structures for the Compact Linear Collider (CLIC) - wakefieldmore » damping in the Power Extraction and Transfer Structure (PETS) and power transfer to the main beam accelerating structures are investigated.« less

[Crystallography of ATP hydrolysis mechanism in rat brain kinesin].

PubMed

Wan, Qun; Zhu, Pingting; Lü, Houning; Chen, Xinhong

2014-04-01

Rat brain kinesin is a conventional kinesin that uses the energy from ATP hydrolysis to walk along the microtubule progressively. Studying how the chemical energy in ATP is utilized for mechanical movement is important to understand this moving function. The monomeric motor domain, rK354, was crystallized. An ATP analog, AMPPNP, was soaked in the active site. Comparing the complex structure of rK354 x AMPPNP and that of rK354ADP, a hypothesis is proposed that Glu237 in the Switch II region sensors the presence of gamma-phosphate and transfers the signal to the microtubule binding region.

The Investigation of Optimal Discrete Approximations for Real Time Flight Simulations

NASA Technical Reports Server (NTRS)

Parrish, E. A.; Mcvey, E. S.; Cook, G.; Henderson, K. C.

1976-01-01

The results are presented of an investigation of discrete approximations for real time flight simulation. Major topics discussed include: (1) consideration of the particular problem of approximation of continuous autopilots by digital autopilots; (2) use of Bode plots and synthesis of transfer functions by asymptotic fits in a warped frequency domain; (3) an investigation of the various substitution formulas, including the effects of nonlinearities; (4) use of pade approximation to the solution of the matrix exponential arising from the discrete state equations; and (5) an analytical integration of the state equation using interpolated input.

Control and design heat flux bending in thermal devices with transformation optics.

PubMed

Xu, Guoqiang; Zhang, Haochun; Jin, Yan; Li, Sen; Li, Yao

2017-04-17

We propose a fundamental latent function of control heat transfer and heat flux density vectors at random positions on thermal materials by applying transformation optics. The expressions for heat flux bending are obtained, and the factors influencing them are investigated in both 2D and 3D cloaking schemes. Under certain conditions, more than one degree of freedom of heat flux bending exists corresponding to the temperature gradients of the 3D domain. The heat flux path can be controlled in random space based on the geometrical azimuths, radial positions, and thermal conductivity ratios of the selected materials.

Time multiplexing based extended depth of focus imaging.

PubMed

Ilovitsh, Asaf; Zalevsky, Zeev

2016-01-01

We propose to utilize the time multiplexing super resolution method to extend the depth of focus of an imaging system. In standard time multiplexing, the super resolution is achieved by generating duplication of the optical transfer function in the spectrum domain, by the use of moving gratings. While this improves the spatial resolution, it does not increase the depth of focus. By changing the gratings frequency and, by that changing the duplication positions, it is possible to obtain an extended depth of focus. The proposed method is presented analytically, demonstrated via numerical simulations and validated by a laboratory experiment.

Dynamic modeling and parameter estimation of a radial and loop type distribution system network

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

Jun Qui; Heng Chen; Girgis, A.A.

1993-05-01

This paper presents a new identification approach to three-phase power system modeling and model reduction taking power system network as multi-input, multi-output (MIMO) processes. The model estimate can be obtained in discrete-time input-output form, discrete- or continuous-time state-space variable form, or frequency-domain impedance transfer function matrix form. An algorithm for determining the model structure of this MIMO process is described. The effect of measurement noise on the approach is also discussed. This approach has been applied on a sample system and simulation results are also presented in this paper.

Structural and mechanistic insights into phospholipid transfer by Ups1–Mdm35 in mitochondria

PubMed Central

Watanabe, Yasunori; Tamura, Yasushi; Kawano, Shin; Endo, Toshiya

2015-01-01

Eukaryotic cells are compartmentalized into membrane-bounded organelles whose functions rely on lipid trafficking to achieve membrane-specific compositions of lipids. Here we focused on the Ups1–Mdm35 system, which mediates phosphatidic acid (PA) transfer between the outer and inner mitochondrial membranes, and determined the X-ray structures of Mdm35 and Ups1–Mdm35 with and without PA. The Ups1–Mdm35 complex constitutes a single domain that has a deep pocket and flexible Ω-loop lid. Structure-based mutational analyses revealed that a basic residue at the pocket bottom and the Ω-loop lid are important for PA extraction from the membrane following Ups1 binding. Ups1 binding to the membrane is enhanced by the dissociation of Mdm35. We also show that basic residues around the pocket entrance are important for Ups1 binding to the membrane and PA extraction. These results provide a structural basis for understanding the mechanism of PA transfer between mitochondrial membranes. PMID:26235513

Reflection high-energy electron diffraction measurements of reciprocal space structure of 2D materials.

PubMed

Xiang, Y; Guo, F-W; Lu, T-M; Wang, G-C

2016-12-02

Knowledge on the symmetry and perfection of a 2D material deposited or transferred to a surface is very important and valuable. We demonstrate a method to map the reciprocal space structure of 2D materials using reflection high energy diffraction (RHEED). RHEED from a 2D material gives rise to 'streaks' patterns. It is shown that from these streaks patterns at different azimuthal rotation angles that the reciprocal space intensity distribution can be constructed as a function of momentum transfer parallel to the surface. To illustrate the principle, we experimentally constructed the reciprocal space structure of a commercial graphene/SiO 2 /Si sample in which the graphene layer was transferred to the SiO 2 /Si substrate after it was deposited on a Cu foil by chemical vapor deposition. The result reveals a 12-fold symmetry of the graphene layer which is a result of two dominant orientation domains with 30° rotation relative to each other. We show that the graphene can serve as a template to grow other materials such as a SnS film that follows the symmetry of graphene.

Benefits of computer-based memory and attention training in healthy older adults.

PubMed

Chambon, Caroline; Herrera, Cathy; Romaiguere, Patricia; Paban, Véronique; Alescio-Lautier, Béatrice

2014-09-01

Multifactorial cognitive training programs have a positive effect on cognition in healthy older adults. Among the age-sensitive cognitive domains, episodic memory is the most affected. In the present study, we evaluated the benefits on episodic memory of a computer-based memory and attention training. We targeted consciously controlled processes at encoding and minimizing processing at retrieval, by using more familiarity than recollection during recognition. Such an approach emphasizes processing at encoding and prevents subjects from reinforcing their own errors. Results showed that the training improved recognition performances and induced near transfer to recall. The largest benefits, however, were for tasks with high mental load. Improvement in free recall depended on the modality to recall; semantic recall was improved but not spatial recall. In addition, a far transfer was also observed with better memory self-perception and self-esteem of the participants. Finally, at 6-month follow up, maintenance of benefits was observed only for semantic free recall. The challenge now is to corroborate far transfer by objective measures of everyday life executive functioning. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Type IV pili of Acidithiobacillus ferrooxidans can transfer electrons from extracellular electron donors.

PubMed

Li, Yongquan; Li, Hongyu

2014-03-01

Studies on Acidithiobacillus ferrooxidans accepting electrons from Fe(II) have previously focused on cytochrome c. However, we have discovered that, besides cytochrome c, type IV pili (Tfp) can transfer electrons. Here, we report conduction by Tfp of A. ferrooxidans analyzed with a conducting-probe atomic force microscope (AFM). The results indicate that the Tfp of A. ferrooxidans are highly conductive. The genome sequence of A. ferrooxidans ATCC 23270 contains two genes, pilV and pilW, which code for pilin domain proteins with the conserved amino acids characteristic of Tfp. Multiple alignment analysis of the PilV and PilW (pilin) proteins indicated that pilV is the adhesin gene while pilW codes for the major protein element of Tfp. The likely function of Tfp is to complete the circuit between the cell surface and Fe(II) oxides. These results indicate that Tfp of A. ferrooxidans might serve as biological nanowires transferring electrons from the surface of Fe(II) oxides to the cell surface. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Color transfer between high-dynamic-range images

NASA Astrophysics Data System (ADS)

Hristova, Hristina; Cozot, Rémi; Le Meur, Olivier; Bouatouch, Kadi

2015-09-01

Color transfer methods alter the look of a source image with regards to a reference image. So far, the proposed color transfer methods have been limited to low-dynamic-range (LDR) images. Unlike LDR images, which are display-dependent, high-dynamic-range (HDR) images contain real physical values of the world luminance and are able to capture high luminance variations and finest details of real world scenes. Therefore, there exists a strong discrepancy between the two types of images. In this paper, we bridge the gap between the color transfer domain and the HDR imagery by introducing HDR extensions to LDR color transfer methods. We tackle the main issues of applying a color transfer between two HDR images. First, to address the nature of light and color distributions in the context of HDR imagery, we carry out modifications of traditional color spaces. Furthermore, we ensure high precision in the quantization of the dynamic range for histogram computations. As image clustering (based on light and colors) proved to be an important aspect of color transfer, we analyze it and adapt it to the HDR domain. Our framework has been applied to several state-of-the-art color transfer methods. Qualitative experiments have shown that results obtained with the proposed adaptation approach exhibit less artifacts and are visually more pleasing than results obtained when straightforwardly applying existing color transfer methods to HDR images.

Phase behavior of block copolymers in compressed carbon dioxide and as single domain-layer, nanolithographic etch resists for sub-10 nm pattern transfer

NASA Astrophysics Data System (ADS)

Chandler, Curran Matthew

Diblock copolymers have many interesting properties, which first and foremost include their ability to self-assemble into various ordered, regularly spaced domains with nanometer-scale feature sizes. The work in this dissertation can be logically divided into two parts -- the first and the majority of this work describes the phase behavior of certain block copolymer systems, and the second discusses real applications possible with block copolymer templates. Many compressible fluids have solvent-like properties dependent on fluid pressure and can be used as processing aids similar to liquid solvents. Here, compressed CO2 was shown to swell several thin homopolymer films, including polystyrene and polyisoprene, as measured by high pressure ellipsometry at elevated temperatures and pressures. The ellipsometric technique was modified to produce accurate data at these conditions through a custom pressure vessel design. The order-disorder transition (ODT) temperatures of several poly(styrene-bisoprene) diblock copolymers were also investigated by static birefringence when dilated with compressed CO2. Sorption of CO2 in each copolymer resulted in significant depressions of the ODT temperature as a function of fluid pressure, and the data above was used to estimate the quantitative amount of solvent in each of the diblock copolymers. These depressions were not shown to follow dilution approximation, and showed interesting, exaggerated scaling of the ODT at near-bulk polymer concentrations. The phase behavior of block copolymer surfactants was studied when blended with polymer or small molecule additives capable of selective hydrogen bonds. This work used small angle X-ray scattering (SAXS) to identify several low molecular weight systems with strong phase separation and ordered domains as small as 2--3 nanometers upon blending. One blend of a commercially-available surfactant with a small molecule additive was further developed and showed promise as a thin-film pattern transfer template. In this scenario, block copolymer thin films on domain thick with self-assembled feature sizes of only 6--7 nm were used as plasma etch resists. Here the block copolymer's pattern was successfully transferred into the underlying SiO2 substrate using CF4--based reactive ion etching. The result was a parallel, cylindrical nanostructure etched into SiO2.

Brain signal variability as a window into the bidirectionality between music and language processing: moving from a linear to a nonlinear model

PubMed Central

Hutka, Stefanie; Bidelman, Gavin M.; Moreno, Sylvain

2013-01-01

There is convincing empirical evidence for bidirectional transfer between music and language, such that experience in either domain can improve mental processes required by the other. This music-language relationship has been studied using linear models (e.g., comparing mean neural activity) that conceptualize brain activity as a static entity. The linear approach limits how we can understand the brain’s processing of music and language because the brain is a nonlinear system. Furthermore, there is evidence that the networks supporting music and language processing interact in a nonlinear manner. We therefore posit that the neural processing and transfer between the domains of language and music are best viewed through the lens of a nonlinear framework. Nonlinear analysis of neurophysiological activity may yield new insight into the commonalities, differences, and bidirectionality between these two cognitive domains not measurable in the local output of a cortical patch. We thus propose a novel application of brain signal variability (BSV) analysis, based on mutual information and signal entropy, to better understand the bidirectionality of music-to-language transfer in the context of a nonlinear framework. This approach will extend current methods by offering a nuanced, network-level understanding of the brain complexity involved in music-language transfer. PMID:24454295

Brain signal variability as a window into the bidirectionality between music and language processing: moving from a linear to a nonlinear model.

PubMed

Hutka, Stefanie; Bidelman, Gavin M; Moreno, Sylvain

2013-12-30

There is convincing empirical evidence for bidirectional transfer between music and language, such that experience in either domain can improve mental processes required by the other. This music-language relationship has been studied using linear models (e.g., comparing mean neural activity) that conceptualize brain activity as a static entity. The linear approach limits how we can understand the brain's processing of music and language because the brain is a nonlinear system. Furthermore, there is evidence that the networks supporting music and language processing interact in a nonlinear manner. We therefore posit that the neural processing and transfer between the domains of language and music are best viewed through the lens of a nonlinear framework. Nonlinear analysis of neurophysiological activity may yield new insight into the commonalities, differences, and bidirectionality between these two cognitive domains not measurable in the local output of a cortical patch. We thus propose a novel application of brain signal variability (BSV) analysis, based on mutual information and signal entropy, to better understand the bidirectionality of music-to-language transfer in the context of a nonlinear framework. This approach will extend current methods by offering a nuanced, network-level understanding of the brain complexity involved in music-language transfer.

Charge Profile Analysis Reveals That Activation of Pro-apoptotic Regulators Bax and Bak Relies on Charge Transfer Mediated Allosteric Regulation

PubMed Central

Ionescu, Crina-Maria; Svobodová Vařeková, Radka; Prehn, Jochen H. M.; Huber, Heinrich J.; Koča, Jaroslav

2012-01-01

The pro-apoptotic proteins Bax and Bak are essential for executing programmed cell death (apoptosis), yet the mechanism of their activation is not properly understood at the structural level. For the first time in cell death research, we calculated intra-protein charge transfer in order to study the structural alterations and their functional consequences during Bax activation. Using an electronegativity equalization model, we investigated the changes in the Bax charge profile upon activation by a functional peptide of its natural activator protein, Bim. We found that charge reorganizations upon activator binding mediate the exposure of the functional sites of Bax, rendering Bax active. The affinity of the Bax C-domain for its binding groove is decreased due to the Arg94-mediated abrogation of the Ser184-Asp98 interaction. We further identified a network of charge reorganizations that confirms previous speculations of allosteric sensing, whereby the activation information is conveyed from the activation site, through the hydrophobic core of Bax, to the well-distanced functional sites of Bax. The network was mediated by a hub of three residues on helix 5 of the hydrophobic core of Bax. Sequence and structural alignment revealed that this hub was conserved in the Bak amino acid sequence, and in the 3D structure of folded Bak. Our results suggest that allostery mediated by charge transfer is responsible for the activation of both Bax and Bak, and that this might be a prototypical mechanism for a fast activation of proteins during signal transduction. Our method can be applied to any protein or protein complex in order to map the progress of allosteric changes through the proteins' structure. PMID:22719244

Geophysical monitoring of solute transport in dual-domain environments through laboratory experiments, field-scale solute tracer tests, and numerical simulation

NASA Astrophysics Data System (ADS)

Swanson, Ryan David

The advection-dispersion equation (ADE) fails to describe non-Fickian solute transport breakthrough curves (BTCs) in saturated porous media in both laboratory and field experiments, necessitating the use of other models. The dual-domain mass transfer (DDMT) model partitions the total porosity into mobile and less-mobile domains with an exchange of mass between the two domains, and this model can reproduce better fits to BTCs in many systems than ADE-based models. However, direct experimental estimation of DDMT model parameters remains elusive and model parameters are often calculated a posteriori by an optimization procedure. Here, we investigate the use of geophysical tools (direct-current resistivity, nuclear magnetic resonance, and complex conductivity) to estimate these model parameters directly. We use two different samples of the zeolite clinoptilolite, a material shown to demonstrate solute mass transfer due to a significant internal porosity, and provide the first evidence that direct-current electrical methods can track solute movement into and out of a less-mobile pore space in controlled laboratory experiments. We quantify the effects of assuming single-rate DDMT for multirate mass transfer systems. We analyze pore structures using material characterization methods (mercury porosimetry, scanning electron microscopy, and X-ray computer tomography), and compare these observations to geophysical measurements. Nuclear magnetic resonance in conjunction with direct-current resistivity measurements can constrain mobile and less-mobile porosities, but complex conductivity may have little value in relation to mass transfer despite the hypothesis that mass transfer and complex conductivity lengths scales are related. Finally, we conduct a geoelectrical monitored tracer test at the Macrodispersion Experiment (MADE) site in Columbus, MS. We relate hydraulic and electrical conductivity measurements to generate a 3D hydraulic conductivity field, and compare to hydraulic conductivity fields estimated through ordinary kriging and sequential Gaussian simulation. Time-lapse electrical measurements are used to verify or dismiss aspects of breakthrough curves for different hydraulic conductivity fields. Our results quantify the potential for geophysical measurements to infer on single-rate DDMT parameters, show site-specific relations between hydraulic and electrical conductivity, and track solute exchange into and out of less-mobile domains.

SPA- STATISTICAL PACKAGE FOR TIME AND FREQUENCY DOMAIN ANALYSIS

NASA Technical Reports Server (NTRS)

Brownlow, J. D.

1994-01-01

The need for statistical analysis often arises when data is in the form of a time series. This type of data is usually a collection of numerical observations made at specified time intervals. Two kinds of analysis may be performed on the data. First, the time series may be treated as a set of independent observations using a time domain analysis to derive the usual statistical properties including the mean, variance, and distribution form. Secondly, the order and time intervals of the observations may be used in a frequency domain analysis to examine the time series for periodicities. In almost all practical applications, the collected data is actually a mixture of the desired signal and a noise signal which is collected over a finite time period with a finite precision. Therefore, any statistical calculations and analyses are actually estimates. The Spectrum Analysis (SPA) program was developed to perform a wide range of statistical estimation functions. SPA can provide the data analyst with a rigorous tool for performing time and frequency domain studies. In a time domain statistical analysis the SPA program will compute the mean variance, standard deviation, mean square, and root mean square. It also lists the data maximum, data minimum, and the number of observations included in the sample. In addition, a histogram of the time domain data is generated, a normal curve is fit to the histogram, and a goodness-of-fit test is performed. These time domain calculations may be performed on both raw and filtered data. For a frequency domain statistical analysis the SPA program computes the power spectrum, cross spectrum, coherence, phase angle, amplitude ratio, and transfer function. The estimates of the frequency domain parameters may be smoothed with the use of Hann-Tukey, Hamming, Barlett, or moving average windows. Various digital filters are available to isolate data frequency components. Frequency components with periods longer than the data collection interval are removed by least-squares detrending. As many as ten channels of data may be analyzed at one time. Both tabular and plotted output may be generated by the SPA program. This program is written in FORTRAN IV and has been implemented on a CDC 6000 series computer with a central memory requirement of approximately 142K (octal) of 60 bit words. This core requirement can be reduced by segmentation of the program. The SPA program was developed in 1978.

Degree sequence in message transfer

NASA Astrophysics Data System (ADS)

Yamuna, M.

2017-11-01

Message encryption is always an issue in current communication scenario. Methods are being devised using various domains. Graphs satisfy numerous unique properties which can be used for message transfer. In this paper, I propose a message encryption method based on degree sequence of graphs.

Impact of charge-transfer excitons in regioregular polythiophene on the charge separation at polythiophene-fullerene heterojunctions

NASA Astrophysics Data System (ADS)

Polkehn, M.; Tamura, H.; Burghardt, I.

2018-01-01

This study addresses the mechanism of ultrafast charge separation in regioregular oligothiophene-fullerene assemblies representative of poly-3-hexylthiophene (P3HT)-[6,6]-phenyl-C61 butyric acid methyl ester (PCBM) heterojunctions, with special emphasis on the inclusion of charge transfer excitons in the oligothiophene phase. The formation of polaronic inter-chain charge separated species in highly ordered oligothiophene has been demonstrated in recent experiments and could have a significant impact on the net charge transfer to the fullerene acceptor. The present approach combines a first-principles parametrized multi-site Hamiltonian, based on time-dependent density functional theory calculations, with accurate quantum dynamics simulations using the multi-layer multi-configuration time-dependent Hartree method. Quantum dynamical studies are carried out for up to 182 electronic states and 112 phonon modes. The present analysis follows up on our previous study of (Huix-Rotllant et al 2015 J. Phys. Chem. Lett. 6 1702) and significantly expands the scope of this analysis by including the dynamical role of charge transfer excitons. Our investigation highlights the pronounced mixing of photogenerated Frenkel excitons with charge transfer excitons in the oligothiophene domain, and the opening of new transfer channels due the creation of such charge-separated species. As a result, it turns out that the interfacial donor/acceptor charge transfer state can be largely circumvented due to the presence of charge transfer excitons. However, the latter states in turn act as a trap, such that the free carrier yield observed on ultrafast time scales is tangibly reduced. The present analysis underscores the complexity of the transfer pathways at P3HT-PCBM type junctions.

Protein Interacting with C Kinase 1 (PICK1) Reduces Reinsertion Rates of Interaction Partners Sorted to Rab11-dependent Slow Recycling Pathway*

PubMed Central

Madsen, Kenneth L.; Thorsen, Thor S.; Rahbek-Clemmensen, Troels; Eriksen, Jacob; Gether, Ulrik

2012-01-01

The scaffolding protein PICK1 (protein interacting with C kinase 1) contains an N-terminal PSD-95/Discs large/ZO-1 (PDZ) domain and a central lipid-binding Bin/amphiphysin/Rvs (BAR) domain. PICK1 is thought to regulate trafficking of its PDZ binding partners but different and even opposing functions have been suggested. Here, we apply ELISA-based assays and confocal microscopy in HEK293 cells with inducible PICK1 expression to assess in an isolated system the ability of PICK1 to regulate trafficking of natural and engineered PDZ binding partners. The dopamine transporter (DAT), which primarily sorts to degradation upon internalization, did not form perinuclear clusters with PICK1, and PICK1 did not affect DAT internalization/recycling. However, transfer of the PICK1-binding DAT C terminus to the β2-adrenergic receptor, which sorts to recycling upon internalization, led to formation of PICK1 co-clusters in Rab11-positive compartments. Furthermore, PICK1 inhibited Rab11-mediated recycling of the receptor in a BAR and PDZ domain-dependent manner. In contrast, transfer of the DAT C terminus to the δ-opioid receptor, which sorts to degradation, did not result in PICK1 co-clusters or any change in internalization/recycling. Further support for a role of PICK1 determined by its PDZ cargo was obtained for the PICK1 interaction partner prolactin-releasing peptide receptor (GPR10). GPR10 co-localized with Rab11 and clustered with PICK1 upon constitutive internalization but co-localized with the late endosomal marker Rab7 and did not cluster with PICK1 upon agonist-induced internalization. Our data suggest a selective role of PICK1 in clustering and reducing the recycling rates of PDZ domain binding partners sorted to the Rab11-dependent recycling pathway. PMID:22303009

Chemiluminescent and chemiluminescence resonance energy transfer (CRET) detection of DNA, metal ions, and aptamer-substrate complexes using hemin/G-quadruplexes and CdSe/ZnS quantum dots.

PubMed

Freeman, Ronit; Liu, Xiaoqing; Willner, Itamar

2011-08-03

Nucleic acid subunits consisting of fragments of the horseradish peroxidase (HRP)-mimicking DNAzyme and aptamer domains against ATP or sequences recognizing Hg(2+) ions self-assemble, in the presence of ATP or Hg(2+), into the active hemin-G-quadruplex DNAzyme structure. The DNAzyme-generated chemiluminescence provides the optical readout for the sensing events. In addition, the DNAzyme-stimulated chemiluminescence resonance energy transfer (CRET) to CdSe/ZnS quantum dots (QDs) is implemented to develop aptamer or DNA sensing platforms. The self-assembly of the ATP-aptamer subunits/hemin-G-quadruplex DNAzyme, where one of the aptamer subunits is functionalized with CdSe/ZnS QDs, leads to the CRET signal. Also, the functionalization of QDs with a hairpin nucleic acid that includes the G-quadruplex sequence in a ''caged'' configuration is used to analyze DNA. The opening of the hairpin structure by the target DNA assembles the hemin-G-quadruplex DNAzyme that stimulates the CRET signal. By the application of three different sized QDs functionalized with different hairpins, the multiplexed analysis of three different DNA targets is demonstrated by the generation of three different CRET luminescence signals.

Can Driving-Simulator Training Enhance Visual Attention, Cognition, and Physical Functioning in Older Adults?

PubMed

Haeger, Mathias; Bock, Otmar; Memmert, Daniel; Hüttermann, Stefanie

2018-01-01

Virtual reality offers a good possibility for the implementation of real-life tasks in a laboratory-based training or testing scenario. Thus, a computerized training in a driving simulator offers an ecological valid training approach. Visual attention had an influence on driving performance, so we used the reverse approach to test the influence of a driving training on visual attention and executive functions. Thirty-seven healthy older participants (mean age: 71.46 ± 4.09; gender: 17 men and 20 women) took part in our controlled experimental study. We examined transfer effects from a four-week driving training (three times per week) on visual attention, executive function, and motor skill. Effects were analyzed using an analysis of variance with repeated measurements. Therefore, main factors were group and time to show training-related benefits of our intervention. Results revealed improvements for the intervention group in divided visual attention; however, there were benefits neither in the other cognitive domains nor in the additional motor task. Thus, there are no broad training-induced transfer effects from such an ecologically valid training regime. This lack of findings could be addressed to insufficient training intensities or a participant-induced bias following the cancelled randomization process.

Multilayer thin-film phantoms for axial contrast transfer function measurement in optical coherence tomography.

PubMed

Agrawal, Anant; Chen, Chao-Wei; Baxi, Jigesh; Chen, Yu; Pfefer, T Joshua

2013-07-01

In optical coherence tomography (OCT), axial resolution is one of the most critical parameters impacting image quality. It is commonly measured by determining the point spread function (PSF) based on a specular surface reflection. The contrast transfer function (CTF) provides more insights into an imaging system's resolving characteristics and can be readily generated in a system-independent manner, without consideration for image pixel size. In this study, we developed a test method for determination of CTF based on multi-layer, thin-film phantoms, evaluated using spectral- and time-domain OCT platforms with different axial resolution values. Phantoms representing six spatial frequencies were fabricated and imaged. The fabrication process involved spin coating silicone films with precise thicknesses in the 8-40 μm range. Alternating layers were doped with a specified concentration of scattering particles. Validation of layer optical properties and thicknesses were achieved with spectrophotometry and stylus profilometry, respectively. OCT B-scans were used to calculate CTFs and results were compared with convetional PSF measurements based on specular reflections. Testing of these phantoms indicated that our approach can provide direct access to axial resolution characteristics highly relevant to image quality. Furthermore, tissue phantoms based on our thin-film fabrication approach may have a wide range of additional applications in optical imaging and spectroscopy.

Redox-linked Conformational Dynamics in Apoptosis Inducing Factor

PubMed Central

Sevrioukova, Irina F.

2009-01-01

Apoptosis inducing factor (AIF) is a bifunctional mitochondrial flavoprotein critical for energy metabolism and induction of caspase-independent apoptosis, whose exact role in normal mitochondria remains unknown. Upon reduction with NADH, AIF undergoes dimerization and forms tight, long-lived FADH2-NAD charge-transfer complexes (CTC) proposed to be functionally important. To get a deeper insight into structure/function relations and redox mechanism of this vitally important protein, we determined the x-ray structures of oxidized and NADH-reduced forms of naturally folded recombinant murine AIF. Our structures reveal that CTC with the pyridine nucleotide is stabilized by (i) π-stacking interactions between coplanar nicotinamide, isoalloxazine and Phe309 rings, (ii) rearrangement of multiple aromatic residues in the C-terminal domain, likely serving as an electron delocalization site, and (iii) an extensive hydrogen-bonding network involving His453, a key residue undergoing a conformational switch to directly interact and orient the nicotinamide in position optimal for charge transfer. Via the His453-containing peptide, redox changes in the active site are transmitted to the surface, promoting AIF dimerization and restricting access to a primary nuclear localization signal through which the apoptogenic form is transported to the nucleus. Structural findings agree with the biochemical data and support the hypothesis that both normal and apoptogenic functions of AIF are controlled by NADH. PMID:19447115

Insight into structural rearrangements and interdomain interactions related to electron transfer between flavin mononucleotide and heme in nitric oxide synthase: A molecular dynamics study.

PubMed

Sheng, Yinghong; Zhong, Linghao; Guo, Dahai; Lau, Gavin; Feng, Changjian

2015-12-01

Calmodulin (CaM) binding to nitric oxide synthase (NOS) enables a conformational change, in which the FMN domain shuttles between the FAD and heme domains to deliver electrons to the active site heme center. A clear understanding of this large conformational change is critical, since this step is the rate-limiting in NOS catalysis. Herein molecular dynamics simulations were conducted on a model of an oxygenase/FMN (oxyFMN) construct of human inducible NOS (iNOS). This is to investigate the structural rearrangements and the domain interactions related to the FMN-heme interdomain electron transfer (IET). We carried out simulations on the iNOS oxyFMN·CaM complex models in [Fe(III)][FMNH(-)] and [Fe(II)][FMNH] oxidation states, the pre- and post-IET states. The comparison of the dynamics and conformations of the iNOS construct at the two oxidation states has allowed us to identify key factors related to facilitating the FMN-heme IET process. The computational results demonstrated, for the first time, that the conformational change is redox-dependent. Predictions of the key interacting sites in optimal interdomain FMN/heme docking are well supported by experimental data in the literature. An intra-subunit pivot region is predicted to modulate the FMN domain motion and correlate with existence of a bottleneck in the conformational sampling that leads to the electron transfer-competent state. Interactions of the residues identified in this work are proposed to ensure that the FMN domain moves with appropriate degrees of freedom and docks to proper positions at the heme domain, resulting in efficient IET and nitric oxide production. Copyright © 2015 Elsevier Inc. All rights reserved.

Electron transfer flavoprotein domain II orientation monitored using double electron-electron resonance between an enzymatically reduced, native FAD cofactor, and spin labels

PubMed Central

Swanson, Michael A; Kathirvelu, Velavan; Majtan, Tomas; Frerman, Frank E; Eaton, Gareth R; Eaton, Sandra S

2011-01-01

Human electron transfer flavoprotein (ETF) is a soluble mitochondrial heterodimeric flavoprotein that links fatty acid β-oxidation to the main respiratory chain. The crystal structure of human ETF bound to medium chain acyl-CoA dehydrogenase indicates that the flavin adenine dinucleotide (FAD) domain (αII) is mobile, which permits more rapid electron transfer with donors and acceptors by providing closer access to the flavin and allows ETF to accept electrons from at least 10 different flavoprotein dehydrogenases. Sequence homology is high and low-angle X-ray scattering is identical for Paracoccus denitrificans (P. denitrificans) and human ETF. To characterize the orientations of the αII domain of P. denitrificans ETF, distances between enzymatically reduced FAD and spin labels in the three structural domains were measured by double electron-electron resonance (DEER) at X- and Q-bands. An FAD to spin label distance of 2.8 ± 0.15 nm for the label in the FAD-containing αII domain (A210C) agreed with estimates from the crystal structure (3.0 nm), molecular dynamics simulations (2.7 nm), and rotamer library analysis (2.8 nm). Distances between the reduced FAD and labels in αI (A43C) were between 4.0 and 4.5 ± 0.35 nm and for βIII (A111C) the distance was 4.3 ± 0.15 nm. These values were intermediate between estimates from the crystal structure of P. denitrificans ETF and a homology model based on substrate-bound human ETF. These distances suggest that the αII domain adopts orientations in solution that are intermediate between those which are observed in the crystal structures of free ETF (closed) and ETF bound to a dehydrogenase (open). PMID:21308847

Essential role of the flexible linker on the conformational equilibrium of bacterial peroxiredoxin reductase for effective regeneration of peroxiredoxin

PubMed Central

Kamariah, Neelagandan; Eisenhaber, Birgit; Eisenhaber, Frank; Grüber, Gerhard

2017-01-01

Reactive oxygen species (ROS) can damage DNA, proteins, and lipids, so cells have antioxidant systems that regulate ROS. In many bacteria, a dedicated peroxiredoxin reductase, alkyl hydroperoxide reductase subunit F (AhpF), catalyzes the rapid reduction of the redox-active disulfide center of the antioxidant protein peroxiredoxin (AhpC) to detoxify ROS such as hydrogen peroxide, organic hydroperoxide, and peroxynitrite. AhpF is a flexible multidomain protein that enables a series of electron transfers among the redox centers by accepting reducing equivalents from NADH. A flexible linker connecting the N-terminal domain (NTD) and C-terminal domain (CTD) of AhpF suggests that the enzyme adopts a large-scale domain motion that alternates between the closed and open states to shuttle electrons from the CTD via the NTD to AhpC. Here, we conducted comprehensive mutational, biochemical, and biophysical analyses to gain insights into the role of the flexible linker and the residues critical for the domain motions of Escherichia coli AhpF (EcAhpF) during electron transfer. Small-angle X-ray scattering studies of linker mutants revealed that a group of charged residues, 200EKR202, is crucial for the swiveling motion of the NTD. Moreover, NADH binding significantly affected EcAhpF flexibility and the movement of the NTD relative to the CTD. The mutants also exhibited a decrease in H2O2 reduction by the AhpF-AhpC ensemble. We propose that a concerted movement involving the NTD, C-terminal NADH, and FAD domains, and the flexible linker between them is essential for optimal intra-domain cross-talk and for efficient electron transfer to the redox partner AhpC required for peroxidation. PMID:28270505

Big Data Smart Socket (BDSS): a system that abstracts data transfer habits from end users.

PubMed

Watts, Nicholas A; Feltus, Frank A

2017-02-15

The ability to centralize and store data for long periods on an end user's computational resources is increasingly difficult for many scientific disciplines. For example, genomics data is increasingly large and distributed, and the data needs to be moved into workflow execution sites ranging from lab workstations to the cloud. However, the typical user is not always informed on emerging network technology or the most efficient methods to move and share data. Thus, the user defaults to using inefficient methods for transfer across the commercial internet. To accelerate large data transfer, we created a tool called the Big Data Smart Socket (BDSS) that abstracts data transfer methodology from the user. The user provides BDSS with a manifest of datasets stored in a remote storage repository. BDSS then queries a metadata repository for curated data transfer mechanisms and optimal path to move each of the files in the manifest to the site of workflow execution. BDSS functions as a standalone tool or can be directly integrated into a computational workflow such as provided by the Galaxy Project. To demonstrate applicability, we use BDSS within a biological context, although it is applicable to any scientific domain. BDSS is available under version 2 of the GNU General Public License at https://github.com/feltus/BDSS . ffeltus@clemson.edu. © The Author 2016. Published by Oxford University Press.

Big Data Smart Socket (BDSS): a system that abstracts data transfer habits from end users

PubMed Central

Watts, Nicholas A.

2017-01-01

Motivation: The ability to centralize and store data for long periods on an end user’s computational resources is increasingly difficult for many scientific disciplines. For example, genomics data is increasingly large and distributed, and the data needs to be moved into workflow execution sites ranging from lab workstations to the cloud. However, the typical user is not always informed on emerging network technology or the most efficient methods to move and share data. Thus, the user defaults to using inefficient methods for transfer across the commercial internet. Results: To accelerate large data transfer, we created a tool called the Big Data Smart Socket (BDSS) that abstracts data transfer methodology from the user. The user provides BDSS with a manifest of datasets stored in a remote storage repository. BDSS then queries a metadata repository for curated data transfer mechanisms and optimal path to move each of the files in the manifest to the site of workflow execution. BDSS functions as a standalone tool or can be directly integrated into a computational workflow such as provided by the Galaxy Project. To demonstrate applicability, we use BDSS within a biological context, although it is applicable to any scientific domain. Availability and Implementation: BDSS is available under version 2 of the GNU General Public License at https://github.com/feltus/BDSS. Contact: ffeltus@clemson.edu PMID:27797780

MicroRNA Intercellular Transfer and Bioelectrical Regulation of Model Multicellular Ensembles by the Gap Junction Connectivity.

PubMed

Cervera, Javier; Meseguer, Salvador; Mafe, Salvador

2017-08-17

We have studied theoretically the microRNA (miRNA) intercellular transfer through voltage-gated gap junctions in terms of a biophysically grounded system of coupled differential equations. Instead of modeling a specific system, we use a general approach describing the interplay between the genetic mechanisms and the single-cell electric potentials. The dynamics of the multicellular ensemble are simulated under different conditions including spatially inhomogeneous transcription rates and local intercellular transfer of miRNAs. These processes result in spatiotemporal changes of miRNA, mRNA, and ion channel protein concentrations that eventually modify the bioelectrical states of small multicellular domains because of the ensemble average nature of the electrical potential. The simulations allow a qualitative understanding of the context-dependent nature of the effects observed when specific signaling molecules are transferred through gap junctions. The results suggest that an efficient miRNA intercellular transfer could permit the spatiotemporal control of small cellular domains by the conversion of single-cell genetic and bioelectric states into multicellular states regulated by the gap junction interconnectivity.

Vectorial finite elements for solving the radiative transfer equation

NASA Astrophysics Data System (ADS)

Badri, M. A.; Jolivet, P.; Rousseau, B.; Le Corre, S.; Digonnet, H.; Favennec, Y.

2018-06-01

The discrete ordinate method coupled with the finite element method is often used for the spatio-angular discretization of the radiative transfer equation. In this paper we attempt to improve upon such a discretization technique. Instead of using standard finite elements, we reformulate the radiative transfer equation using vectorial finite elements. In comparison to standard finite elements, this reformulation yields faster timings for the linear system assemblies, as well as for the solution phase when using scattering media. The proposed vectorial finite element discretization for solving the radiative transfer equation is cross-validated against a benchmark problem available in literature. In addition, we have used the method of manufactured solutions to verify the order of accuracy for our discretization technique within different absorbing, scattering, and emitting media. For solving large problems of radiation on parallel computers, the vectorial finite element method is parallelized using domain decomposition. The proposed domain decomposition method scales on large number of processes, and its performance is unaffected by the changes in optical thickness of the medium. Our parallel solver is used to solve a large scale radiative transfer problem of the Kelvin-cell radiation.