A statistical model of the human core-temperature circadian rhythm

NASA Technical Reports Server (NTRS)

Brown, E. N.; Choe, Y.; Luithardt, H.; Czeisler, C. A.

2000-01-01

We formulate a statistical model of the human core-temperature circadian rhythm in which the circadian signal is modeled as a van der Pol oscillator, the thermoregulatory response is represented as a first-order autoregressive process, and the evoked effect of activity is modeled with a function specific for each circadian protocol. The new model directly links differential equation-based simulation models and harmonic regression analysis methods and permits statistical analysis of both static and dynamical properties of the circadian pacemaker from experimental data. We estimate the model parameters by using numerically efficient maximum likelihood algorithms and analyze human core-temperature data from forced desynchrony, free-run, and constant-routine protocols. By representing explicitly the dynamical effects of ambient light input to the human circadian pacemaker, the new model can estimate with high precision the correct intrinsic period of this oscillator ( approximately 24 h) from both free-run and forced desynchrony studies. Although the van der Pol model approximates well the dynamical features of the circadian pacemaker, the optimal dynamical model of the human biological clock may have a harmonic structure different from that of the van der Pol oscillator.

Experimental study of complex mixed-mode oscillations generated in a Bonhoeffer-van der Pol oscillator under weak periodic perturbation

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

Shimizu, Kuniyasu, E-mail: kuniyasu.shimizu@it-chiba.ac.jp; Sekikawa, Munehisa; Inaba, Naohiko

2015-02-15

Bifurcations of complex mixed-mode oscillations denoted as mixed-mode oscillation-incrementing bifurcations (MMOIBs) have frequently been observed in chemical experiments. In a previous study [K. Shimizu et al., Physica D 241, 1518 (2012)], we discovered an extremely simple dynamical circuit that exhibits MMOIBs. Our model was represented by a slow/fast Bonhoeffer-van der Pol circuit under weak periodic perturbation near a subcritical Andronov-Hopf bifurcation point. In this study, we experimentally and numerically verify that our dynamical circuit captures the essence of the underlying mechanism causing MMOIBs, and we observe MMOIBs and chaos with distinctive waveforms in real circuit experiments.

Genuine Quantum Signatures in Synchronization of Anharmonic Self-Oscillators.

PubMed

Lörch, Niels; Amitai, Ehud; Nunnenkamp, Andreas; Bruder, Christoph

2016-08-12

We study the synchronization of a Van der Pol self-oscillator with Kerr anharmonicity to an external drive. We demonstrate that the anharmonic, discrete energy spectrum of the quantum oscillator leads to multiple resonances in both phase locking and frequency entrainment not present in the corresponding classical system. Strong driving close to these resonances leads to nonclassical steady-state Wigner distributions. Experimental realizations of these genuine quantum signatures can be implemented with current technology.

Polynomial law for controlling the generation of n-scroll chaotic attractors in an optoelectronic delayed oscillator

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

Márquez, Bicky A., E-mail: bmarquez@ivic.gob.ve; Suárez-Vargas, José J., E-mail: jjsuarez@ivic.gob.ve; Ramírez, Javier A.

2014-09-01

Controlled transitions between a hierarchy of n-scroll attractors are investigated in a nonlinear optoelectronic oscillator. Using the system's feedback strength as a control parameter, it is shown experimentally the transition from Van der Pol-like attractors to 6-scroll, but in general, this scheme can produce an arbitrary number of scrolls. The complexity of every state is characterized by Lyapunov exponents and autocorrelation coefficients.

Chaotic Oscillations of Second Order Linear Hyperbolic Equations with Nonlinear Boundary Conditions: A Factorizable but Noncommutative Case

NASA Astrophysics Data System (ADS)

Li, Liangliang; Huang, Yu; Chen, Goong; Huang, Tingwen

If a second order linear hyperbolic partial differential equation in one-space dimension can be factorized as a product of two first order operators and if the two first order operators commute, with one boundary condition being the van der Pol type and the other being linear, one can establish the occurrence of chaos when the parameters enter a certain regime [Chen et al., 2014]. However, if the commutativity of the two first order operators fails to hold, then the treatment in [Chen et al., 2014] no longer works and significant new challenges arise in determining nonlinear boundary conditions that engenders chaos. In this paper, we show that by incorporating a linear memory effect, a nonlinear van der Pol boundary condition can cause chaotic oscillations when the parameter enters a certain regime. Numerical simulations illustrating chaotic oscillations are also presented.

Perturbation analysis of the limit cycle of the free van der Pol equation

NASA Technical Reports Server (NTRS)

Dadfar, M. B.; Geer, J.; Anderson, C. M.

1983-01-01

A power series expansion in the damping parameter, epsilon, of the limit cycle of the free van der Pol equation is constructed and analyzed. Coefficients in the expansion are computed in exact rational arithmetic using the symbolic manipulation system MACSYMA and using a FORTRAN program. The series is analyzed using Pade approximants. The convergence of the series for the maximum amplitude of the limit cycle is limited by two pair of complex conjugate singularities in the complex epsilon-plane. A new expansion parameter is introduced which maps these singularities to infinity and leads to a new expansion for the amplitude which converges for all real values of epsilon. Amplitudes computed from this transformed series agree very well with reported numerical and asymptotic results. For the limit cycle itself, convergence of the series expansion is limited by three pair of complex conjugate branch point singularities. Two pair remain fixed throughout the cycle, and correspond to the singularities found in the maximum amplitude series, while the third pair moves in the epsilon-plane as a function of t from one of the fixed pairs to the other. The limit cycle series is transformed using a new expansion parameter, which leads to a new series that converges for larger values of epsilon.

Synchronization in counter-rotating oscillators.

PubMed

Bhowmick, Sourav K; Ghosh, Dibakar; Dana, Syamal K

2011-09-01

An oscillatory system can have opposite senses of rotation, clockwise or anticlockwise. We present a general mathematical description of how to obtain counter-rotating oscillators from the definition of a dynamical system. A type of mixed synchronization emerges in counter-rotating oscillators under diffusive scalar coupling when complete synchronization and antisynchronization coexist in different state variables. We present numerical examples of limit cycle van der Pol oscillator and chaotic Rössler and Lorenz systems. Stability conditions of mixed synchronization are analytically obtained for both Rössler and Lorenz systems. Experimental evidences of counter-rotating limit cycle and chaotic oscillators and mixed synchronization are given in electronic circuits.

Mikrobielle Kurzzeitteste zur Bestimmung der mutagenen Potenz chemischer Substanzen

NASA Astrophysics Data System (ADS)

Gericke, Dietmar

1983-04-01

During the last 20 years it became much more interesting to test new chemicals as fast as possible for their carcinogenic potency. Therefore new test models were developed. Mutagenicity seems to be one sign for carcinogenicity. Therefore test systems using microorganisms were studied which are influenced by mutagenic substances. These systems are described, first of all the Ames-Test, using revertants of Salmonella typhimurium, secondly the Escherichia coli system deficient of DNA-polymerase A (DNA-Pol A-). The yeast Saccharomyces cerevisiae was introduced some years ago and finally the Neurospora crassa system serves as an additional test to define exactly the localisation of mutations. The tests and their problems are discussed.

Torus Breakdown and Homoclinic Chaos in a Glow Discharge Tube

NASA Astrophysics Data System (ADS)

Ginoux, Jean-Marc; Meucci, Riccardo; Euzzor, Stefano

2017-12-01

Starting from historical researches, we used, like Van der Pol and Le Corbeiller, a cubic function for modeling the current-voltage characteristic of a direct current low-pressure plasma discharge tube, i.e. a neon tube. This led us to propose a new four-dimensional autonomous dynamical system allowing to describe the experimentally observed phenomenon. Then, mathematical analysis and detailed numerical investigations of such a fourth-order torus circuit enabled to highlight bifurcation routes from torus breakdown to homoclinic chaos following the Newhouse-Ruelle-Takens scenario.

Enroute NASA/FAA low-frequency propfan test in Alabama (October 1987): A versatile atmospheric aircraft long-range noise prediction system

NASA Astrophysics Data System (ADS)

Tsouka, Despina G.

In order to obtain a flight-to-static noise prediction of an advanced Turboprop (propfan) Aircraft, FAA went on an elaboration of the data that were measured during a full scale measuring program that was conducted by NASA and FAA/DOT/TSC on October 1987 in Alabama. The elaboration process was based on aircraft simulation to a point source, on an atmospheric two dimensional noise model, on the American National Standard algorithm for the calculation of atmospheric absortion, and on the DOT/TSC convention for ground reflection effects. Using the data of the Alabama measurements, the present paper examines the development of a generalized, flexible and more accurate process for the evaluation of the static and flight low-frequency long-range noise data. This paper also examines the applicability of the assumptions made by the Integrated Noise Model about linear propagation, of the three dimensional Hamiltonian Rays Tracing model and of the Weyl-Van der Pol model. The model proposes some assumptions in order to increase the calculations flexibility without significant loss of accuracy. In addition, it proposes the usage of the three dimensional Hamiltonian Rays Tracing model and the Weyl-Van der Pol model in order to increase the accuracy and to ensure the generalization of noise propagation prediction over grounds with variable impedance.

Synchronous Oscillations in Van Der Pol Generator with Modulated Natural Frequency

NASA Astrophysics Data System (ADS)

Nimets, A. Yu.; Vavriv, D. M.

2015-12-01

The synchronous operation of Van Der Pole generator with the low-frequency modulated natural frequency has been investigated. The presence of low-frequency modulation is shown to lead to formation of additional synchronization regions. The appearance of such regions is found to be caused by threefrequency resonances resulted from the interaction between oscillations of the generator natural frequency, modulation frequency and synchronized signal frequency. Characteristics of synchronous oscillations due to the below mentioned three-frequency interaction are obtained and comparison with the case of synchronization of oscillator on the main mode made.

Blades Forced Vibration Under Aero-Elastic Excitation Modeled by Van der Pol

NASA Astrophysics Data System (ADS)

Pust, Ladislav; Pesek, Ludek

This paper employs a new analytical approach to model the influence of aerodynamic excitation on the dynamics of a bladed cascade at the flutter state. The flutter is an aero-elastic phenomenon that is linked to the interaction of the flow and the traveling deformation wave in the cascade when only the damping of the cascade changes. As a case study the dynamic properties of the five-blade-bunch excited by the running harmonic external forces and aerodynamic self-excited forces are investigated. This blade-bunch is linked in the shroud by means of the viscous-elastic damping elements. The external running excitation depends on the ratio of stator and rotor blade numbers and corresponds to the real type of excitation in the steam turbine. The aerodynamic self-excited forces are modeled by two types of Van der Pol nonlinear models. The influence of the interaction of both types of self-excitation with the external running excitation is investigated on the response curves.

Sitnikov problem in the cyclic kite configuration

NASA Astrophysics Data System (ADS)

Shahbaz Ullah, M.; Bhatnagar, K. B.; Hassan, M. R.

2014-12-01

This manuscript deals with the development of the series solutions of the Sitnikov kite configuration by the methods given of Lindstedt-Poincarė, using Green's function and MacMillan. Next we have developed averaged equation of motion by applying the Van der Pol transformation and averaging technique of Guckenheimer and Holmes (Nonlinear oscillations, dynamical system bifurcations of vector fields. Springer, Berlin, 1983). In addition to the resonance criterion at the 3/2 commensurability we have chosen ω=2 n/3, n=2, ω is the angular velocity of the coordinate system. Lastly the periodicity of the solutions has been examined by the Poincarė section.

Simulations of pattern dynamics for reaction-diffusion systems via SIMULINK.

PubMed

Wang, Kaier; Steyn-Ross, Moira L; Steyn-Ross, D Alistair; Wilson, Marcus T; Sleigh, Jamie W; Shiraishi, Yoichi

2014-04-11

Investigation of the nonlinear pattern dynamics of a reaction-diffusion system almost always requires numerical solution of the system's set of defining differential equations. Traditionally, this would be done by selecting an appropriate differential equation solver from a library of such solvers, then writing computer codes (in a programming language such as C or Matlab) to access the selected solver and display the integrated results as a function of space and time. This "code-based" approach is flexible and powerful, but requires a certain level of programming sophistication. A modern alternative is to use a graphical programming interface such as Simulink to construct a data-flow diagram by assembling and linking appropriate code blocks drawn from a library. The result is a visual representation of the inter-relationships between the state variables whose output can be made completely equivalent to the code-based solution. As a tutorial introduction, we first demonstrate application of the Simulink data-flow technique to the classical van der Pol nonlinear oscillator, and compare Matlab and Simulink coding approaches to solving the van der Pol ordinary differential equations. We then show how to introduce space (in one and two dimensions) by solving numerically the partial differential equations for two different reaction-diffusion systems: the well-known Brusselator chemical reactor, and a continuum model for a two-dimensional sheet of human cortex whose neurons are linked by both chemical and electrical (diffusive) synapses. We compare the relative performances of the Matlab and Simulink implementations. The pattern simulations by Simulink are in good agreement with theoretical predictions. Compared with traditional coding approaches, the Simulink block-diagram paradigm reduces the time and programming burden required to implement a solution for reaction-diffusion systems of equations. Construction of the block-diagram does not require high-level programming skills, and the graphical interface lends itself to easy modification and use by non-experts.

Cooperative Adaptive Output Regulation for Second-Order Nonlinear Multiagent Systems With Jointly Connected Switching Networks.

PubMed

Liu, Wei; Huang, Jie

2018-03-01

This paper studies the cooperative global robust output regulation problem for a class of heterogeneous second-order nonlinear uncertain multiagent systems with jointly connected switching networks. The main contributions consist of the following three aspects. First, we generalize the result of the adaptive distributed observer from undirected jointly connected switching networks to directed jointly connected switching networks. Second, by performing a new coordinate and input transformation, we convert our problem into the cooperative global robust stabilization problem of a more complex augmented system via the distributed internal model principle. Third, we solve the stabilization problem by a distributed state feedback control law. Our result is illustrated by the leader-following consensus problem for a group of Van der Pol oscillators.

Simulation of noisy dynamical system by Deep Learning

NASA Astrophysics Data System (ADS)

Yeo, Kyongmin

2017-11-01

Deep learning has attracted huge attention due to its powerful representation capability. However, most of the studies on deep learning have been focused on visual analytics or language modeling and the capability of the deep learning in modeling dynamical systems is not well understood. In this study, we use a recurrent neural network to model noisy nonlinear dynamical systems. In particular, we use a long short-term memory (LSTM) network, which constructs internal nonlinear dynamics systems. We propose a cross-entropy loss with spatial ridge regularization to learn a non-stationary conditional probability distribution from a noisy nonlinear dynamical system. A Monte Carlo procedure to perform time-marching simulations by using the LSTM is presented. The behavior of the LSTM is studied by using noisy, forced Van der Pol oscillator and Ikeda equation.

Distributed Coordinated Control of Large-Scale Nonlinear Networks

DOE PAGES

Kundu, Soumya; Anghel, Marian

2015-11-08

We provide a distributed coordinated approach to the stability analysis and control design of largescale nonlinear dynamical systems by using a vector Lyapunov functions approach. In this formulation the large-scale system is decomposed into a network of interacting subsystems and the stability of the system is analyzed through a comparison system. However finding such comparison system is not trivial. In this work, we propose a sum-of-squares based completely decentralized approach for computing the comparison systems for networks of nonlinear systems. Moreover, based on the comparison systems, we introduce a distributed optimal control strategy in which the individual subsystems (agents) coordinatemore » with their immediate neighbors to design local control policies that can exponentially stabilize the full system under initial disturbances.We illustrate the control algorithm on a network of interacting Van der Pol systems.« less

Duffing's Equation and Nonlinear Resonance

ERIC Educational Resources Information Center

Fay, Temple H.

2003-01-01

The phenomenon of nonlinear resonance (sometimes called the "jump phenomenon") is examined and second-order van der Pol plane analysis is employed to indicate that this phenomenon is not a feature of the equation, but rather the result of accumulated round-off error, truncation error and algorithm error that distorts the true bounded solution onto…

Oscillations and Rolling for Duffing's Equation

NASA Astrophysics Data System (ADS)

Aref'eva, I. Ya.; Piskovskiy, E. V.; Volovich, I. V.

2013-01-01

The Duffing equation has been used to model nonlinear dynamics not only in mechanics and electronics but also in biology and in neurology for the brain process modeling. Van der Pol's method is often used in nonlinear dynamics to improve perturbation theory results when describing small oscillations. However, in some other problems of nonlinear dynamics particularly in case of Duffing-Higgs equation in field theory, for the Einsten-Friedmann equations in cosmology and for relaxation processes in neurology not only small oscillations regime is of interest but also the regime of slow rolling. In the present work a method for approximate solution to nonlinear dynamics equations in the rolling regime is developed. It is shown that in order to improve perturbation theory in the rolling regime it turns out to be effective to use an expansion in hyperbolic functions instead of trigonometric functions as it is done in van der Pol's method in case of small oscillations. In particular the Duffing equation in the rolling regime is investigated using solution expressed in terms of elliptic functions. Accuracy of obtained approximation is estimated. The Duffing equation with dissipation is also considered.

Simulations of pattern dynamics for reaction-diffusion systems via SIMULINK

PubMed Central

2014-01-01

Background Investigation of the nonlinear pattern dynamics of a reaction-diffusion system almost always requires numerical solution of the system’s set of defining differential equations. Traditionally, this would be done by selecting an appropriate differential equation solver from a library of such solvers, then writing computer codes (in a programming language such as C or Matlab) to access the selected solver and display the integrated results as a function of space and time. This “code-based” approach is flexible and powerful, but requires a certain level of programming sophistication. A modern alternative is to use a graphical programming interface such as Simulink to construct a data-flow diagram by assembling and linking appropriate code blocks drawn from a library. The result is a visual representation of the inter-relationships between the state variables whose output can be made completely equivalent to the code-based solution. Results As a tutorial introduction, we first demonstrate application of the Simulink data-flow technique to the classical van der Pol nonlinear oscillator, and compare Matlab and Simulink coding approaches to solving the van der Pol ordinary differential equations. We then show how to introduce space (in one and two dimensions) by solving numerically the partial differential equations for two different reaction-diffusion systems: the well-known Brusselator chemical reactor, and a continuum model for a two-dimensional sheet of human cortex whose neurons are linked by both chemical and electrical (diffusive) synapses. We compare the relative performances of the Matlab and Simulink implementations. Conclusions The pattern simulations by Simulink are in good agreement with theoretical predictions. Compared with traditional coding approaches, the Simulink block-diagram paradigm reduces the time and programming burden required to implement a solution for reaction-diffusion systems of equations. Construction of the block-diagram does not require high-level programming skills, and the graphical interface lends itself to easy modification and use by non-experts. PMID:24725437

Chimera states in complex networks: interplay of fractal topology and delay

NASA Astrophysics Data System (ADS)

Sawicki, Jakub; Omelchenko, Iryna; Zakharova, Anna; Schöll, Eckehard

2017-06-01

Chimera states are an example of intriguing partial synchronization patterns emerging in networks of identical oscillators. They consist of spatially coexisting domains of coherent (synchronized) and incoherent (desynchronized) dynamics. We analyze chimera states in networks of Van der Pol oscillators with hierarchical connectivities, and elaborate the role of time delay introduced in the coupling term. In the parameter plane of coupling strength and delay time we find tongue-like regions of existence of chimera states alternating with regions of existence of coherent travelling waves. We demonstrate that by varying the time delay one can deliberately stabilize desired spatio-temporal patterns in the system.

Mutual information as an order parameter for quantum synchronization

NASA Astrophysics Data System (ADS)

Ameri, V.; Eghbali-Arani, M.; Mari, A.; Farace, A.; Kheirandish, F.; Giovannetti, V.; Fazio, R.

2015-01-01

Spontaneous synchronization is a fundamental phenomenon, important in many theoretical studies and applications. Recently, this effect has been analyzed and observed in a number of physical systems close to the quantum-mechanical regime. In this work we propose mutual information as a useful order parameter which can capture the emergence of synchronization in very different contexts, ranging from semiclassical to intrinsically quantum-mechanical systems. Specifically, we first study the synchronization of two coupled Van der Pol oscillators in both classical and quantum regimes and later we consider the synchronization of two qubits inside two coupled optical cavities. In all these contexts, we find that mutual information can be used as an appropriate figure of merit for determining the synchronization phases independently of the specific details of the system.

Design and testing of a magnetic suspension and damping system for a space telescope

NASA Technical Reports Server (NTRS)

Ockman, N. J.

1972-01-01

The basic equations of motion are derived for a two dimensional, three degree of freedom simulation of a space telescope coupled to a spacecraft by means of a magnetic suspension and isolation system. The system consists of paramagnetic or ferromagnetic discs confined to the magnetic field between two Helmholtz coils. Damping is introduced by varying the magnetic field in proportion to a velocity signal derived from the telescope. The equations of motion are nonlinear, similar in behavior to the one-dimensional Van der Pol equation. The computer simulation was verified by testing a 264-kilogram air bearing platform which simulates the telescope in a frictionless environment. The simulation demonstrated effective isolation capabilities for disturbance frequencies above resonance. Damping in the system improved the response near resonance and prevented the build-up of large oscillatory amplitudes.

Closed-loop suppression of chaos in nonlinear driven oscillators

NASA Astrophysics Data System (ADS)

Aguirre, L. A.; Billings, S. A.

1995-05-01

This paper discusses the suppression of chaos in nonlinear driven oscillators via the addition of a periodic perturbation. Given a system originally undergoing chaotic motions, it is desired that such a system be driven to some periodic orbit. This can be achieved by the addition of a weak periodic signal to the oscillator input. This is usually accomplished in open loop, but this procedure presents some difficulties which are discussed in the paper. To ensure that this is attained despite uncertainties and possible disturbances on the system, a procedure is suggested to perform control in closed loop. In addition, it is illustrated how a model, estimated from input/output data, can be used in the design. Numerical examples which use the Duffing-Ueda and modified van der Pol oscillators are included to illustrate some of the properties of the new approach.

Fuzzy controller training using particle swarm optimization for nonlinear system control.

PubMed

Karakuzu, Cihan

2008-04-01

This paper proposes and describes an effective utilization of particle swarm optimization (PSO) to train a Takagi-Sugeno (TS)-type fuzzy controller. Performance evaluation of the proposed fuzzy training method using the obtained simulation results is provided with two samples of highly nonlinear systems: a continuous stirred tank reactor (CSTR) and a Van der Pol (VDP) oscillator. The superiority of the proposed learning technique is that there is no need for a partial derivative with respect to the parameter for learning. This fuzzy learning technique is suitable for real-time implementation, especially if the system model is unknown and a supervised training cannot be run. In this study, all parameters of the controller are optimized with PSO in order to prove that a fuzzy controller trained by PSO exhibits a good control performance.

Synchronization between two coupled direct current glow discharge plasma sources

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

Chaubey, Neeraj; Mukherjee, S.; Sen, A.

2015-02-15

Experimental results on the nonlinear dynamics of two coupled glow discharge plasma sources are presented. A variety of nonlinear phenomena including frequency synchronization and frequency pulling are observed as the coupling strength is varied. Numerical solutions of a model representation of the experiment consisting of two coupled asymmetric Van der Pol type equations are found to be in good agreement with the observed results.

Emergent global oscillations in heterogeneous excitable media: The example of pancreatic β cells

NASA Astrophysics Data System (ADS)

Cartwright, Julyan H. E.

2000-07-01

Using the standard van der Pol-FitzHugh-Nagumo excitable medium model, I demonstrate a generic mechanism, diversity, that provokes the emergence of global oscillations from individually quiescent elements in heterogeneous excitable media. This mechanism may be operating in the mammalian pancreas, where excitable β cells, quiescent when isolated, are found to oscillate when coupled, despite the absence of a pacemaker region.

Mode suppression of a two-dimensional potential relaxation instability in a weakly magnetized discharge plasma

NASA Astrophysics Data System (ADS)

Gyergyek, T.; Čerček, M.; Jelić, N.; Stanojević, M.

1993-05-01

A potential relaxation instability (PRI) is modulated by an external signal using an additional grid to modulate the radial plasma potential profile in a magnetized plasma column in a linear magnetized discharge plasma device. It is observed that the electrode current oscillations follow the van der Pol equation with an external forcing term, and the linear growth rate of the instability is measured.

Evaluation of dynamical models: dissipative synchronization and other techniques.

PubMed

Aguirre, Luis Antonio; Furtado, Edgar Campos; Tôrres, Leonardo A B

2006-12-01

Some recent developments for the validation of nonlinear models built from data are reviewed. Besides giving an overall view of the field, a procedure is proposed and investigated based on the concept of dissipative synchronization between the data and the model, which is very useful in validating models that should reproduce dominant dynamical features, like bifurcations, of the original system. In order to assess the discriminating power of the procedure, four well-known benchmarks have been used: namely, Duffing-Ueda, Duffing-Holmes, and van der Pol oscillators, plus the Hénon map. The procedure, developed for discrete-time systems, is focused on the dynamical properties of the model, rather than on statistical issues. For all the systems investigated, it is shown that the discriminating power of the procedure is similar to that of bifurcation diagrams--which in turn is much greater than, say, that of correlation dimension--but at a much lower computational cost.

Learning-Based Adaptive Optimal Tracking Control of Strict-Feedback Nonlinear Systems.

PubMed

Gao, Weinan; Jiang, Zhong-Ping; Weinan Gao; Zhong-Ping Jiang; Gao, Weinan; Jiang, Zhong-Ping

2018-06-01

This paper proposes a novel data-driven control approach to address the problem of adaptive optimal tracking for a class of nonlinear systems taking the strict-feedback form. Adaptive dynamic programming (ADP) and nonlinear output regulation theories are integrated for the first time to compute an adaptive near-optimal tracker without any a priori knowledge of the system dynamics. Fundamentally different from adaptive optimal stabilization problems, the solution to a Hamilton-Jacobi-Bellman (HJB) equation, not necessarily a positive definite function, cannot be approximated through the existing iterative methods. This paper proposes a novel policy iteration technique for solving positive semidefinite HJB equations with rigorous convergence analysis. A two-phase data-driven learning method is developed and implemented online by ADP. The efficacy of the proposed adaptive optimal tracking control methodology is demonstrated via a Van der Pol oscillator with time-varying exogenous signals.

Renormalization Group for nonlinear oscillators in the absence of linear restoring force

NASA Astrophysics Data System (ADS)

Sarkar, A.; Bhattacharjee, J. K.

2010-09-01

Perturbative Renormalization Group (RG) has been very useful in probing periodic orbits in two-dimensional dynamical systems (Sarkar A., Bhattacharjee J. K., Chakraborty S. and Banerjee D., arXiv:1005.2858v1 (2010)). The method relies on finding a linear center, around which perturbation analysis is done. However it is not obvious as to how systems devoid of any linear terms may be approached using this method. We propose here how RG can be done even in the absence of linear terms. We successfully apply the method to extract correct results for a variant of the second-order Riccati equation. In this variant the periodic orbit disappears as a parameter is varied. Our RG captures this disappearance correctly. We have also applied the technique successfully on the force-free Van der Pol-Duffing oscillator.

Optimal design of tweezer control for chimera states

NASA Astrophysics Data System (ADS)

Omelchenko, Iryna; Omel'chenko, Oleh E.; Zakharova, Anna; Schöll, Eckehard

2018-01-01

Chimera states are complex spatio-temporal patterns which consist of coexisting domains of spatially coherent and incoherent dynamics in systems of coupled oscillators. In small networks, chimera states usually exhibit short lifetimes and erratic drifting of the spatial position of the incoherent domain. A tweezer feedback control scheme can stabilize and fix the position of chimera states. We analyze the action of the tweezer control in small nonlocally coupled networks of Van der Pol and FitzHugh-Nagumo oscillators, and determine the ranges of optimal control parameters. We demonstrate that the tweezer control scheme allows for stabilization of chimera states with different shapes, and can be used as an instrument for controlling the coherent domains size, as well as the maximum average frequency difference of the oscillators.

Direction of Coupling from Phases of Interacting Oscillators: A Permutation Information Approach

NASA Astrophysics Data System (ADS)

Bahraminasab, A.; Ghasemi, F.; Stefanovska, A.; McClintock, P. V. E.; Kantz, H.

2008-02-01

We introduce a directionality index for a time series based on a comparison of neighboring values. It can distinguish unidirectional from bidirectional coupling, as well as reveal and quantify asymmetry in bidirectional coupling. It is tested on a numerical model of coupled van der Pol oscillators, and applied to cardiorespiratory data from healthy subjects. There is no need for preprocessing and fine-tuning the parameters, which makes the method very simple, computationally fast and robust.

Nonlinear Constitutive Modeling of Piezoelectric Ceramics

NASA Astrophysics Data System (ADS)

Xu, Jia; Li, Chao; Wang, Haibo; Zhu, Zhiwen

2017-12-01

Nonlinear constitutive modeling of piezoelectric ceramics is discussed in this paper. Van der Pol item is introduced to explain the simple hysteretic curve. Improved nonlinear difference items are used to interpret the hysteresis phenomena of piezoelectric ceramics. The fitting effect of the model on experimental data is proved by the partial least-square regression method. The results show that this method can describe the real curve well. The results of this paper are helpful to piezoelectric ceramics constitutive modeling.

Compilation of Abstracts of Theses Submitted By Candidates for Degrees

DTIC Science & Technology

1990-09-30

based on a relationship between the Chaos methods ( the Poincare section and Van der Pol plane ) and the vibration amplitude and phase was discovered... half subsampled fields scored well and the one-eighth fields were poor. Even in the latter case, the model filled data gaps and areas of cyclonic and...flight test of a half scale unmanned air vehicle was conducted for the purpose of predicting the londgitudinal and laternal-directional behavior of

Stability diagram for the forced Kuramoto model.

PubMed

Childs, Lauren M; Strogatz, Steven H

2008-12-01

We analyze the periodically forced Kuramoto model. This system consists of an infinite population of phase oscillators with random intrinsic frequencies, global sinusoidal coupling, and external sinusoidal forcing. It represents an idealization of many phenomena in physics, chemistry, and biology in which mutual synchronization competes with forced synchronization. In other words, the oscillators in the population try to synchronize with one another while also trying to lock onto an external drive. Previous work on the forced Kuramoto model uncovered two main types of attractors, called forced entrainment and mutual entrainment, but the details of the bifurcations between them were unclear. Here we present a complete bifurcation analysis of the model for a special case in which the infinite-dimensional dynamics collapse to a two-dimensional system. Exact results are obtained for the locations of Hopf, saddle-node, and Takens-Bogdanov bifurcations. The resulting stability diagram bears a striking resemblance to that for the weakly nonlinear forced van der Pol oscillator.

Heuristics for the Hodgkin-Huxley system.

PubMed

Hoppensteadt, Frank

2013-09-01

Hodgkin and Huxley (HH) discovered that voltages control ionic currents in nerve membranes. This led them to describe electrical activity in a neuronal membrane patch in terms of an electronic circuit whose characteristics were determined using empirical data. Due to the complexity of this model, a variety of heuristics, including relaxation oscillator circuits and integrate-and-fire models, have been used to investigate activity in neurons, and these simpler models have been successful in suggesting experiments and explaining observations. Connections between most of the simpler models had not been made clear until recently. Shown here are connections between these heuristics and the full HH model. In particular, we study a new model (Type III circuit): It includes the van der Pol-based models; it can be approximated by a simple integrate-and-fire model; and it creates voltages and currents that correspond, respectively, to the h and V components of the HH system. Copyright © 2012 Elsevier Inc. All rights reserved.

Connection between three-body configuration and four-body configuration of the Sitnikov problem when one of the masses approaches zero: circular case

NASA Astrophysics Data System (ADS)

Shahbaz Ullah, M.; Hassan, M. R.

2014-09-01

In this manuscript we have established averaged equation of motion of the Sitnikov restricted three- body and four-body problem when all the primaries are point masses, by applying the Van der Pol transformation and averaging technique of J. Guckenheimer and P. Holmes (in Nonlinear Oscillations, Dynamical System Bifurcations of Vector Fields, Springer, Berlin, 1983). In addition to the resonance criterion at the 3/2 commensurability we have chosen ω=2 n/3, n=4, ω is the angular velocity of the coordinate system. Further we established the Series solution of the three-body and four-body problem in the sense of Sitnikov. Lastly the periodicities of the solutions have been examined by the Poincare section and four-body and three-body problem have been compared by different comparative graphs and surfaces.

Dynamics of multi-frequency oscillator ensembles with resonant coupling

NASA Astrophysics Data System (ADS)

Lück, S.; Pikovsky, A.

2011-07-01

We study dynamics of populations of resonantly coupled oscillators having different frequencies. Starting from the coupled van der Pol equations we derive the Kuramoto-type phase model for the situation, where the natural frequencies of two interacting subpopulations are in relation 2:1. Depending on the parameter of coupling, ensembles can demonstrate fully synchronous clusters, partial synchrony (only one subpopulation synchronizes), or asynchrony in both subpopulations. Theoretical description of the dynamics based on the Watanabe-Strogatz approach is developed.

Wavelets, non-linearity and turbulence in fusion plasmas

NASA Astrophysics Data System (ADS)

van Milligen, B. Ph.

Introduction Linear spectral analysis tools Wavelet analysis Wavelet spectra and coherence Joint wavelet phase-frequency spectra Non-linear spectral analysis tools Wavelet bispectra and bicoherence Interpretation of the bicoherence Analysis of computer-generated data Coupled van der Pol oscillators A large eddy simulation model for two-fluid plasma turbulence A long wavelength plasma drift wave model Analysis of plasma edge turbulence from Langmuir probe data Radial coherence observed on the TJ-IU torsatron Bicoherence profile at the L/H transition on CCT Conclusions

A pictorial study of an invariant torus in phase space of four dimensions.

NASA Technical Reports Server (NTRS)

Baxter, R.; Eiserike, H.; Stokes, A.

1972-01-01

An investigation was conducted with the aid of a computer graphics device at Goddard Space Flight Center to study the behavior of the invariant manifolds of a particular fourth-order equation, as a parameter in the equation is varied over the interval from 0 to 1. The equation consists of two coupled Van der Pol equations. For a small parameter value, the manifold is an asymptotically stable torus, where the flow on the torus is simply a rotation. As the value of the parameter is increased, the only thing that changes is the nature of the flow on the torus, which itself persists throughout the parameter variation. It is shown that ultimately the four periodic cycles which appear play a more significant part in the phase profile of the system than does the torus itself.

Fitting Nonlinear Ordinary Differential Equation Models with Random Effects and Unknown Initial Conditions Using the Stochastic Approximation Expectation-Maximization (SAEM) Algorithm.

PubMed

Chow, Sy-Miin; Lu, Zhaohua; Sherwood, Andrew; Zhu, Hongtu

2016-03-01

The past decade has evidenced the increased prevalence of irregularly spaced longitudinal data in social sciences. Clearly lacking, however, are modeling tools that allow researchers to fit dynamic models to irregularly spaced data, particularly data that show nonlinearity and heterogeneity in dynamical structures. We consider the issue of fitting multivariate nonlinear differential equation models with random effects and unknown initial conditions to irregularly spaced data. A stochastic approximation expectation-maximization algorithm is proposed and its performance is evaluated using a benchmark nonlinear dynamical systems model, namely, the Van der Pol oscillator equations. The empirical utility of the proposed technique is illustrated using a set of 24-h ambulatory cardiovascular data from 168 men and women. Pertinent methodological challenges and unresolved issues are discussed.

Comparison of Virtual Oscillator and Droop Control: Preprint

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

Johnson, Brian B; Rodriguez, Miguel; Dhople, Sairaj

Virtual oscillator control and droop control are two techniques that can be used to ensure synchronization and power sharing of parallel inverters in islanded operation. VOC relies on the implementation of non-linear Van der Pol oscillator equations in the control system of the inverter, acting upon the time-domain instantaneous inverter current and terminal voltage. On the other hand, DC explicitly computes active and reactive power produced by the inverter and relies on limited bandwidth low-pass filters. Even though both methods can be engineered to produce the same steady-state characteristics, their dynamic performances are significantly different. This paper presents analytical andmore » experimental results that aim to compare both methods. It is shown that VOC is inherently faster and enables minimizing the circulating currents. The results are verified using three 120V, 1kW inverters.« less

Long-Term Dynamics of Autonomous Fractional Differential Equations

NASA Astrophysics Data System (ADS)

Liu, Tao; Xu, Wei; Xu, Yong; Han, Qun

This paper aims to investigate long-term dynamic behaviors of autonomous fractional differential equations with effective numerical method. The long-term dynamic behaviors predict where systems are heading after long-term evolution. We make some modification and transplant cell mapping methods to autonomous fractional differential equations. The mapping time duration of cell mapping is enlarged to deal with the long memory effect. Three illustrative examples, i.e. fractional Lotka-Volterra equation, fractional van der Pol oscillator and fractional Duffing equation, are studied with our revised generalized cell mapping method. We obtain long-term dynamics, such as attractors, basins of attraction, and saddles. Compared with some existing stability and numerical results, the validity of our method is verified. Furthermore, we find that the fractional order has its effect on the long-term dynamics of autonomous fractional differential equations.

FITTING NONLINEAR ORDINARY DIFFERENTIAL EQUATION MODELS WITH RANDOM EFFECTS AND UNKNOWN INITIAL CONDITIONS USING THE STOCHASTIC APPROXIMATION EXPECTATION–MAXIMIZATION (SAEM) ALGORITHM

PubMed Central

Chow, Sy- Miin; Lu, Zhaohua; Zhu, Hongtu; Sherwood, Andrew

2014-01-01

The past decade has evidenced the increased prevalence of irregularly spaced longitudinal data in social sciences. Clearly lacking, however, are modeling tools that allow researchers to fit dynamic models to irregularly spaced data, particularly data that show nonlinearity and heterogeneity in dynamical structures. We consider the issue of fitting multivariate nonlinear differential equation models with random effects and unknown initial conditions to irregularly spaced data. A stochastic approximation expectation–maximization algorithm is proposed and its performance is evaluated using a benchmark nonlinear dynamical systems model, namely, the Van der Pol oscillator equations. The empirical utility of the proposed technique is illustrated using a set of 24-h ambulatory cardiovascular data from 168 men and women. Pertinent methodological challenges and unresolved issues are discussed. PMID:25416456

On the Computation of Finite Invariant Sets of Mappings.

DTIC Science & Technology

1988-02-01

for the calculation of such invariant cycles. We refer here only to Doedel [1], looss et al [3], Kevrekidis et al [4], Van Veldhuizen ,[6], where further... van Veldhuizen , On Polygonal Approximations of an Invariant Curve, Dept.of Mathem. and Comp. Science, Vrije Universiteit Amsterdam, Techni- cal Report 1987, Math. Comp. to appear DATE Fl .LMED ...of van der Pol’s equation " x2) x - A(l - x ) X’ + x - 0 (16) As shown, for example in [2], the solution satisfies x - 2 cos(wt)+ A (0.75 sin(wt

Resonant frequency calculations using a hybrid perturbation-Galerkin technique

NASA Technical Reports Server (NTRS)

Geer, James F.; Andersen, Carl M.

1991-01-01

A two-step hybrid perturbation Galerkin technique is applied to the problem of determining the resonant frequencies of one or several degree of freedom nonlinear systems involving a parameter. In one step, the Lindstedt-Poincare method is used to determine perturbation solutions which are formally valid about one or more special values of the parameter (e.g., for large or small values of the parameter). In step two, a subset of the perturbation coordinate functions determined in step one is used in Galerkin type approximation. The technique is illustrated for several one degree of freedom systems, including the Duffing and van der Pol oscillators, as well as for the compound pendulum. For all of the examples considered, it is shown that the frequencies obtained by the hybrid technique using only a few terms from the perturbation solutions are significantly more accurate than the perturbation results on which they are based, and they compare very well with frequencies obtained by purely numerical methods.

Emergence of amplitude death scenario in a network of oscillators under repulsive delay interaction

NASA Astrophysics Data System (ADS)

Bera, Bidesh K.; Hens, Chittaranjan; Ghosh, Dibakar

2016-07-01

We report the existence of amplitude death in a network of identical oscillators under repulsive mean coupling. Amplitude death appears in a globally coupled network of identical oscillators with instantaneous repulsive mean coupling only when the number of oscillators is more than two. We further investigate that, amplitude death may emerge even in two coupled oscillators as well as network of oscillators if we introduce delay time in the repulsive mean coupling. We have analytically derived the region of amplitude death island and find out how strength of delay controls the death regime in two coupled or a large network of coupled oscillators. We have verified our results on network of delayed Mackey-Glass systems where parameters are set in hyperchaotic regime. We have also tested our coupling approach in two paradigmatic limit cycle oscillators: Stuart-Landau and Van der Pol oscillators.

Delay-induced stochastic bifurcations in a bistable system under white noise

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

Sun, Zhongkui, E-mail: sunzk@nwpu.edu.cn; Fu, Jin; Xu, Wei

2015-08-15

In this paper, the effects of noise and time delay on stochastic bifurcations are investigated theoretically and numerically in a time-delayed Duffing-Van der Pol oscillator subjected to white noise. Due to the time delay, the random response is not Markovian. Thereby, approximate methods have been adopted to obtain the Fokker-Planck-Kolmogorov equation and the stationary probability density function for amplitude of the response. Based on the knowledge that stochastic bifurcation is characterized by the qualitative properties of the steady-state probability distribution, it is found that time delay and feedback intensity as well as noise intensity will induce the appearance of stochasticmore » P-bifurcation. Besides, results demonstrated that the effects of the strength of the delayed displacement feedback on stochastic bifurcation are accompanied by the sensitive dependence on time delay. Furthermore, the results from numerical simulations best confirm the effectiveness of the theoretical analyses.« less

Series-nonuniform rational B-spline signal feedback: From chaos to any embedded periodic orbit or target point.

PubMed

Shao, Chenxi; Xue, Yong; Fang, Fang; Bai, Fangzhou; Yin, Peifeng; Wang, Binghong

2015-07-01

The self-controlling feedback control method requires an external periodic oscillator with special design, which is technically challenging. This paper proposes a chaos control method based on time series non-uniform rational B-splines (SNURBS for short) signal feedback. It first builds the chaos phase diagram or chaotic attractor with the sampled chaotic time series and any target orbit can then be explicitly chosen according to the actual demand. Second, we use the discrete timing sequence selected from the specific target orbit to build the corresponding external SNURBS chaos periodic signal, whose difference from the system current output is used as the feedback control signal. Finally, by properly adjusting the feedback weight, we can quickly lead the system to an expected status. We demonstrate both the effectiveness and efficiency of our method by applying it to two classic chaotic systems, i.e., the Van der Pol oscillator and the Lorenz chaotic system. Further, our experimental results show that compared with delayed feedback control, our method takes less time to obtain the target point or periodic orbit (from the starting point) and that its parameters can be fine-tuned more easily.

Series-nonuniform rational B-spline signal feedback: From chaos to any embedded periodic orbit or target point

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

Shao, Chenxi, E-mail: cxshao@ustc.edu.cn; Xue, Yong; Fang, Fang

2015-07-15

The self-controlling feedback control method requires an external periodic oscillator with special design, which is technically challenging. This paper proposes a chaos control method based on time series non-uniform rational B-splines (SNURBS for short) signal feedback. It first builds the chaos phase diagram or chaotic attractor with the sampled chaotic time series and any target orbit can then be explicitly chosen according to the actual demand. Second, we use the discrete timing sequence selected from the specific target orbit to build the corresponding external SNURBS chaos periodic signal, whose difference from the system current output is used as the feedbackmore » control signal. Finally, by properly adjusting the feedback weight, we can quickly lead the system to an expected status. We demonstrate both the effectiveness and efficiency of our method by applying it to two classic chaotic systems, i.e., the Van der Pol oscillator and the Lorenz chaotic system. Further, our experimental results show that compared with delayed feedback control, our method takes less time to obtain the target point or periodic orbit (from the starting point) and that its parameters can be fine-tuned more easily.« less

A model for predicting aortic dynamic response to -G sub z impact acceleration.

NASA Technical Reports Server (NTRS)

Advani, S. H.; Tarnay, T. J.; Byars, E. F.; Love, J. S.

1972-01-01

A steady state dynamic response model for the radial motion of the aorta is developed from in vivo pressure-displacement and nerve stimulation experiments on canines. The model represented by a modified Van der Pol wave motion oscillator closely predicts steady state and perturbed response results. The applicability of the steady state canine aortic model to tailward acting impact forces is studied by means of the perturbed phase plane of the oscillator. The backflow through the aortic arch resulting from a specified acceleration-time profile is computed and an analysis for predicting the forced motion aortic response is presented.

Compact Polarimetry Potentials

NASA Technical Reports Server (NTRS)

Truong-Loi, My-Linh; Dubois-Fernandez, Pascale; Pottier, Eric

2011-01-01

The goal of this study is to show the potential of a compact-pol SAR system for vegetation applications. Compact-pol concept has been suggested to minimize the system design while maximize the information and is declined as the ?/4, ?/2 and hybrid modes. In this paper, the applications such as biomass and vegetation height estimates are first presented, then, the equivalence between compact-pol data simulated from full-pol data and compact-pol data processed from raw data as such is shown. Finally, a calibration procedure using external targets is proposed.

Chaotic attractors of relaxation oscillators

NASA Astrophysics Data System (ADS)

Guckenheimer, John; Wechselberger, Martin; Young, Lai-Sang

2006-03-01

We develop a general technique for proving the existence of chaotic attractors for three-dimensional vector fields with two time scales. Our results connect two important areas of dynamical systems: the theory of chaotic attractors for discrete two-dimensional Henon-like maps and geometric singular perturbation theory. Two-dimensional Henon-like maps are diffeomorphisms that limit on non-invertible one-dimensional maps. Wang and Young formulated hypotheses that suffice to prove the existence of chaotic attractors in these families. Three-dimensional singularly perturbed vector fields have return maps that are also two-dimensional diffeomorphisms limiting on one-dimensional maps. We describe a generic mechanism that produces folds in these return maps and demonstrate that the Wang-Young hypotheses are satisfied. Our analysis requires a careful study of the convergence of the return maps to their singular limits in the Ck topology for k >= 3. The theoretical results are illustrated with a numerical study of a variant of the forced van der Pol oscillator.

General Linearized Theory of Quantum Fluctuations around Arbitrary Limit Cycles

NASA Astrophysics Data System (ADS)

Navarrete-Benlloch, Carlos; Weiss, Talitha; Walter, Stefan; de Valcárcel, Germán J.

2017-09-01

The theory of Gaussian quantum fluctuations around classical steady states in nonlinear quantum-optical systems (also known as standard linearization) is a cornerstone for the analysis of such systems. Its simplicity, together with its accuracy far from critical points or situations where the nonlinearity reaches the strong coupling regime, has turned it into a widespread technique, being the first method of choice in most works on the subject. However, such a technique finds strong practical and conceptual complications when one tries to apply it to situations in which the classical long-time solution is time dependent, a most prominent example being spontaneous limit-cycle formation. Here, we introduce a linearization scheme adapted to such situations, using the driven Van der Pol oscillator as a test bed for the method, which allows us to compare it with full numerical simulations. On a conceptual level, the scheme relies on the connection between the emergence of limit cycles and the spontaneous breaking of the symmetry under temporal translations. On the practical side, the method keeps the simplicity and linear scaling with the size of the problem (number of modes) characteristic of standard linearization, making it applicable to large (many-body) systems.

Distributed Energy Systems Integration and Demand Optimization for Autonomous Operations and Electric Grid Transactions

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

Ghatikar, Girish; Mashayekh, Salman; Stadler, Michael

Distributed power systems in the U.S. and globally are evolving to provide reliable and clean energy to consumers. In California, existing regulations require significant increases in renewable generation, as well as identification of customer-side distributed energy resources (DER) controls, communication technologies, and standards for interconnection with the electric grid systems. As DER deployment expands, customer-side DER control and optimization will be critical for system flexibility and demand response (DR) participation, which improves the economic viability of DER systems. Current DER systems integration and communication challenges include leveraging the existing DER and DR technology and systems infrastructure, and enabling optimized cost,more » energy and carbon choices for customers to deploy interoperable grid transactions and renewable energy systems at scale. Our paper presents a cost-effective solution to these challenges by exploring communication technologies and information models for DER system integration and interoperability. This system uses open standards and optimization models for resource planning based on dynamic-pricing notifications and autonomous operations within various domains of the smart grid energy system. It identifies architectures and customer engagement strategies in dynamic DR pricing transactions to generate feedback information models for load flexibility, load profiles, and participation schedules. The models are tested at a real site in California—Fort Hunter Liggett (FHL). Furthermore, our results for FHL show that the model fits within the existing and new DR business models and networked systems for transactive energy concepts. Integrated energy systems, communication networks, and modeling tools that coordinate supply-side networks and DER will enable electric grid system operators to use DER for grid transactions in an integrated system.« less

An Analysis of the DER Adoption Climate in Japan UsingOptimization Results for Prototype Buildings with U.S. Comparisons

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

Zhou, Nan; Marnay, Chris; Firestone, Ryan

2006-06-16

This research demonstrates economically optimal distributedenergy resource (DER) system choice using the DER choice and operationsoptimization program, the Distributed Energy Resources Customer AdoptionModel (DER-CAM). DER-CAM finds the optimal combination of installedequipment given prevailing utility tariffs and fuel prices, siteelectrical and thermal loads (including absorption cooling), and a menuof available equipment. It provides a global optimization, albeitidealized, that shows how site useful energy loads can be served atminimum cost. Five prototype Japanese commercial buildings are examinedand DER-CAM is applied to select the economically optimal DER system foreach. Based on the optimization results, energy and emission reductionsare evaluated. Significant decreases in fuelmore » consumption, carbonemissions, and energy costs were seen in the DER-CAM results. Savingswere most noticeable in the prototype sports facility, followed by thehospital, hotel, and office building. Results show that DER with combinedheat and power equipment is a promising efficiency and carbon mitigationstrategy, but that precise system design is necessary. Furthermore, aJapan-U.S. comparison study of policy, technology, and utility tariffsrelevant to DER installation is presented.« less

Dynamical inference: where phase synchronization and generalized synchronization meet.

PubMed

Stankovski, Tomislav; McClintock, Peter V E; Stefanovska, Aneta

2014-06-01

Synchronization is a widespread phenomenon that occurs among interacting oscillatory systems. It facilitates their temporal coordination and can lead to the emergence of spontaneous order. The detection of synchronization from the time series of such systems is of great importance for the understanding and prediction of their dynamics, and several methods for doing so have been introduced. However, the common case where the interacting systems have time-variable characteristic frequencies and coupling parameters, and may also be subject to continuous external perturbation and noise, still presents a major challenge. Here we apply recent developments in dynamical Bayesian inference to tackle these problems. In particular, we discuss how to detect phase slips and the existence of deterministic coupling from measured data, and we unify the concepts of phase synchronization and general synchronization. Starting from phase or state observables, we present methods for the detection of both phase and generalized synchronization. The consistency and equivalence of phase and generalized synchronization are further demonstrated, by the analysis of time series from analog electronic simulations of coupled nonautonomous van der Pol oscillators. We demonstrate that the detection methods work equally well on numerically simulated chaotic systems. In all the cases considered, we show that dynamical Bayesian inference can clearly identify noise-induced phase slips and distinguish coherence from intrinsic coupling-induced synchronization.

Chimeralike states in a network of oscillators under attractive and repulsive global coupling.

PubMed

Mishra, Arindam; Hens, Chittaranjan; Bose, Mridul; Roy, Prodyot K; Dana, Syamal K

2015-12-01

We report chimeralike states in an ensemble of oscillators using a type of global coupling consisting of two components: attractive and repulsive mean-field feedback. We identify the existence of two types of chimeralike states in a bistable Liénard system; in one type, both the coherent and the incoherent populations are in chaotic states (which we refer to as chaos-chaos chimeralike states) and, in another type, the incoherent population is in periodic state while the coherent population has irregular small oscillation. We find a metastable state in a parameter regime of the Liénard system where the coherent and noncoherent states migrate in time from one to another subpopulation. The relative size of the incoherent subpopulation, in the chimeralike states, remains almost stable with increasing size of the network. The generality of the coupling configuration in the origin of the chimeralike states is tested, using a second example of bistable system, the van der Pol-Duffing oscillator where the chimeralike states emerge as weakly chaotic in the coherent subpopulation and chaotic in the incoherent subpopulation. Furthermore, we apply the coupling, in a simplified form, to form a network of the chaotic Rössler system where both the noncoherent and the coherent subpopulations show chaotic dynamics.

National Dam Inspection Program. Lake Lattimore Dam (NDI-ID Number PA-00406, DER-ID Number 52-78) Delaware River Basin, Pike County, Pennsylvania. Phase I Inspection Report.

DTIC Science & Technology

1980-06-01

V 5 - 1i/ .; t (cl S . /40 T POo. t t tv / I? I H 4O/- /o 31. C1 A Lot,- PoL e (6I 3 / - - - v ... S . OFCHKD. BY ------ DATE-------. . .. . . . . . R JE T : f6. SUBJECT --------------------------. PROECT-!. II Ii I V 1:2 ,,.,, - ) ) .( y...DATE/,/’ -’ REEGER ASSOCIATES SHEET NO. 7, CNKD. BY DATE PROJECT SUBJECT t AXtI Ic C / PA; 4 ( It o’,’ ’- ,’ S ’ L V / 4 LA d1A ’l, V HYC4P) 4,A 4, I

Information Interaction Study for DER and DMS Interoperability

NASA Astrophysics Data System (ADS)

Liu, Haitao; Lu, Yiming; Lv, Guangxian; Liu, Peng; Chen, Yu; Zhang, Xinhui

The Common Information Model (CIM) is an abstract data model that can be used to represent the major objects in Distribution Management System (DMS) applications. Because the Common Information Model (CIM) doesn't modeling the Distributed Energy Resources (DERs), it can't meet the requirements of DER operation and management for Distribution Management System (DMS) advanced applications. Modeling of DER were studied based on a system point of view, the article initially proposed a CIM extended information model. By analysis the basic structure of the message interaction between DMS and DER, a bidirectional messaging mapping method based on data exchange was proposed.

Zum Wissenschaftsverständnis der modernen Evolutionsbiologie

NASA Astrophysics Data System (ADS)

Sommer, Ralf J.

Die moderne Evolutionsbiologie hat ihren Ursprung in den Arbeiten von Charles Darwin und Alfred Wallace (Darwin 1963). Der gemeinsame Ausgangspunkt des Evolutionsgedanken ist dabei die Beobachtung, dass die biologische Welt nicht konstant ist. Biologische Systeme und alle darin lebenden Organismen unterliegen über längere Zeiträume hinweg einer stetigen Veränderung. Diese grundlegende Eigenschaft biologischer Systeme macht die Biologie zu einer historischen Wissenschaft und stellt einen wichtigen Gegensatz zu großen Teilen der Physik dar. Obwohl die Aussage von der Veränderlichkeit der Arten heute trivial klingt, war sie im 19. Jahrhundert eine Revolution, da die Konstanz der Arten und der Welt eine vorherrschende Stellung im damaligen Weltbild hatte (Amundson 2005).

Design of a prosumer EMS for energy trading

NASA Astrophysics Data System (ADS)

Hwang, T.; Yoo, Y.; Kang, S.; Lee, I.

2018-03-01

We design a DER management system for energy trading based on OASIS EI and EMIX. With the spread of DERs, there is a growing need of a system for integrated management of DERs and customer loads. In this paper, we give a brief overview of a DER EMS for prosumer energy saving and trading. Based on the OASIS standards, we design a functional architecture of a DER EMS for energy trading. After showing communication protocols and operation sequences, we summarize our works.

Vortex-induced vibrations mitigation through a nonlinear energy sink

NASA Astrophysics Data System (ADS)

Dai, H. L.; Abdelkefi, A.; Wang, L.

2017-01-01

The passive suppression mechanism of the vortex-induced vibrations (VIV) of the cylinder by means of an essentially nonlinear element, the nonlinear energy sink (NES) is investigated. The flow-induced loads on the cylinder are modeled using a prevalent van der Pol oscillator which is experimentally validated, coupling to the structural vibrations in the presence of the NES structure. Based on the coupled nonlinear governing equations of motion, the performed analysis indicates that the mass and damping of NES have significant effects on the coupled frequency and damping of the aero-elastic system, leading to the shift of synchronization region and mitigation of vibration responses. It is demonstrated that the coupled system of flow-cylinder-NES behaves resonant interactions, showing periodic, aperiodic, and multiple stable responses which depend on the values of the NES parameters. In addition, it is found that the occurrence of multiple stable responses can enhance the nonlinear energy pumping effect, resulting in the increment of transferring energy from the flow via the cylinder to the NES, which is related to the essential nonlinearity of the sink stiffness. This results in a significant reduction in the VIV amplitudes of the primary circular cylinder for appropriate NES parameter values.

Sitnikov problem in the square configuration: elliptic case

NASA Astrophysics Data System (ADS)

Shahbaz Ullah, M.

2016-05-01

This paper is extension to the classical Sitnikov problem, when the four primaries of equal masses lie at the vertices of a square for all time and moving in elliptic orbits around their center of mass of the system, the distances between the primaries vary with time but always in such a way that their mutual distances remain in the same ratio. First we have established averaged equation of motion of the Sitnikov five-body problem in the light of Jalali and Pourtakdoust (Celest. Mech. Dyn. Astron. 68:151-162, 1997), by applying the Van der Pol transformation and averaging technique of Guckenheimer and Holmes (Nonlinear oscillations, dynamical system bifurcations of vector fields, Springer, Berlin, 1983). Next the Hamiltonian equation of motion has been solved with the help of action angle variables I and φ. Finally the periodicity and stability of the Sitnikov five-body problem have been examined with the help of Poincare surfaces of section (PSS). It is shown that chaotic region emerging from the destroyed islands, can easily be seen by increasing the eccentricity of the primaries to e = 0.21. It is valid for bounded small amplitude solutions z_{max} ( z_{max} = 0.65 ) and 0 ≤ e < 0.3.

Optimal planning and design of a renewable energy based supply system for microgrids

DOE PAGES

Hafez, Omar; Bhattacharya, Kankar

2012-03-03

This paper presents a technique for optimal planning and design of hybrid renewable energy systems for microgrid applications. The Distributed Energy Resources Customer Adoption Model (DER-CAM) is used to determine the optimal size and type of distributed energy resources (DERs) and their operating schedules for a sample utility distribution system. Using the DER-CAM results, an evaluation is performed to evaluate the electrical performance of the distribution circuit if the DERs selected by the DER-CAM optimization analyses are incorporated. Results of analyses regarding the economic benefits of utilizing the optimal locations identified for the selected DER within the system are alsomore » presented. The actual Brookhaven National Laboratory (BNL) campus electrical network is used as an example to show the effectiveness of this approach. The results show that these technical and economic analyses of hybrid renewable energy systems are essential for the efficient utilization of renewable energy resources for microgird applications.« less

Subunit compositions of Arabidopsis RNA polymerases I and III reveal Pol I- and Pol III-specific forms of the AC40 subunit and alternative forms of the C53 subunit

PubMed Central

Ream, Thomas S.; Haag, Jeremy R.; Pontvianne, Frederic; Nicora, Carrie D.; Norbeck, Angela D.; Paša-Tolić, Ljiljana; Pikaard, Craig S.

2015-01-01

Using affinity purification and mass spectrometry, we identified the subunits of Arabidopsis thaliana multisubunit RNA polymerases I and III (abbreviated as Pol I and Pol III), the first analysis of their physical compositions in plants. In all eukaryotes examined to date, AC40 and AC19 subunits are common to Pol I (a.k.a. Pol A) and Pol III (a.k.a. Pol C) and are encoded by single genes. Surprisingly, A. thaliana and related species express two distinct AC40 paralogs, one of which assembles into Pol I and the other of which assembles into Pol III. Changes at eight amino acid positions correlate with the functional divergence of Pol I- and Pol III-specific AC40 paralogs. Two genes encode homologs of the yeast C53 subunit and either protein can assemble into Pol III. By contrast, only one of two potential C17 variants, and one of two potential C31 variants were detected in Pol III. We introduce a new nomenclature system for plant Pol I and Pol III subunits in which the 12 subunits that are structurally and functionally homologous among Pols I through V are assigned equivalent numbers. PMID:25813043

Phase shifting two coupled circadian pacemakers - Implications for jet lag

NASA Technical Reports Server (NTRS)

Gander, P. H.; Kronauer, R. E.; Graeber, R. C.

1985-01-01

Two Van der Pol oscillators with reciprocal linear velocity coupling are utilized to model the response of the human circadian timing system to abrupt displacements of the environmental time cues (zeitgebers). The core temperature rhythm and sleep-wake cycle simulated by the model are examined. The relationship between the masking of circadian rhythms by environmental variables and behavioral and physiological events and the rates of resynchronization is studied. The effects of zeitgeber phase shifts and zeitgeber strength on the resynchronization rates are analyzed. The influence of intrinsic pacemakers periods and coupling strength on resynchronization are investigated. The simulated data reveal that: resynchronization after a time zone shift depends on the magnitude of the shift; the time of day of the shift has little influence on resynchronization; the strength of zeitgebers affects the rate and direction of the resynchronization; the intrinsic pacemaker periods have a significant effect on resynchronization; and increasing the coupling between the oscillators results in an increase in the rate of resynchronization. The model data are compared to transmeridian flight studies data and similar resynchronization patterns are observed.

Chaos control applied to cardiac rhythms represented by ECG signals

NASA Astrophysics Data System (ADS)

Borem Ferreira, Bianca; Amorim Savi, Marcelo; Souza de Paula, Aline

2014-10-01

The control of irregular or chaotic heartbeats is a key issue in cardiology. In this regard, chaos control techniques represent a good alternative since they suggest treatments different from those traditionally used. This paper deals with the application of the extended time-delayed feedback control method to stabilize pathological chaotic heart rhythms. Electrocardiogram (ECG) signals are employed to represent the cardiovascular behavior. A mathematical model is employed to generate ECG signals using three modified Van der Pol oscillators connected with time delay couplings. This model provides results that qualitatively capture the general behavior of the heart. Controlled ECG signals show the ability of the strategy either to control or to suppress the chaotic heart dynamics generating less-critical behaviors.

In vitro characterization of pol I*, an SOS inducible, error-prone from of Escherichia coli DNA polymerase I

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

Hodes, C.S.

E. coli strains carrying mutations in the SOS regulon were screened for the presence of pol I*. Use of pol I* in assays of polymerase fidelity and selectivity has been limited by the low concentration and purity of the enzyme. Therefore, attempts were made to further concentrate and purify pol I*. The template selectivity of pol I* was compared to that of pol I using three models of damaged DNA. UV-irradiated M13 DNA was used in a two-stage termination reaction to determine if pol I* could bypass putative pyrimidine dimers to a greater extent than pol I. In the gelmore » system no reproducibly significant bypass could be detected by either pol I* or pol I. However, the degree of replication by pol I* utilizing UV-irradiated M13 DNA template, was up to 5-fold greater than for pol I. OsO{sub 4}-oxidized M13 DNA was used as a model substrate for oxidative DNA damage. Opposite this substrate incorporation by pol I* is less inhibited than incorporation by pol I. However, in a test of nucleotide selectivity neither pol I*, pol I, nor terminal deoxyribonucleotidyl transferase will incorporate ({alpha}-{sup 32}P)thymine glycol deoxyribonucleotide. The activity of pol I* was compared to that of pol I on the synthetic templates, poly (dA) and poly((dA)+2-AP). Pol I* misincorporated both dCMP and dGMP to a greater extent than pol I when utilizing templates containing 2-aminopurine deoxyribonucleotide.« less

Influence of laser linewidth and polarization modulator length on polarization shift keying for free space optical communication.

PubMed

Han, Biao; Zhao, Wei; Xie, Xiaoping; Su, Yulong; Wang, Wei; Hu, Hui

2015-04-06

Modulating signal with polarization modulator (PolM) is the simplest method for polarization shift keying (PolSK) in free space optical communication. However, this method has an intrinsic drawback on degree of polarization (DOP) reduction for the existence of polarization mode dispersion (PMD) in PolM. In this work, we analyze this change of DOP and its influence on PolSK using coherency matrix. We demonstrate that the decrease of DOP after PolM will generate extra loss and bit error ratio (BER) for PolSK communication, while this loss and BER will aggravate with the increase of laser linewidth and PolM length. For a practical PolSK system, laser linewidth should be less than 0.008nm.

Subunit compositions of Arabidopsis RNA polymerases I and III reveal Pol I- and Pol III-specific forms of the AC40 subunit and alternative forms of the C53 subunit

DOE PAGES

Ream, Thomas S.; Haag, Jeremy R.; Pontvianne, Frederic; ...

2015-05-02

Using affinity purification and mass spectrometry, we identified the subunits of Arabidopsis thaliana multisubunit RNA Polymerases I and III (abbreviated as Pol I and Pol III), providing the first description of their physical compositions in plants. AC40 and AC19 subunits are typically common to Pol I (a.k.a. Pol A) and Pol III (a.k.a. Pol C) and are encoded by single genes whose mutation, in humans, is a cause of the craniofacial disorder, Treacher-Collins Syndrome. Surprisingly, A. thaliana, and related species, express two distinct AC40 paralogs, one of which assembles into Pol I and the other of which assembles into Polmore » III. Changes at eight amino acid positions correlate with this functional divergence of Pol I and Pol III-specific AC40 paralogs. Two genes encode homologs of the yeast C53 subunit, and either variant can assemble into Pol III. By contrast, only one of two potential C17 variants, and one of two potential C31 variants were detected in Pol III. We introduce a new nomenclature system for plant Pol I and Pol III subunits in which the twelve subunits that are structurally and functionally homologous among Pols I through V are assigned equivalent numbers.« less

Subunit compositions of Arabidopsis RNA polymerases I and III reveal Pol I- and Pol III-specific forms of the AC40 subunit and alternative forms of the C53 subunit

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

Ream, Thomas S.; Haag, Jeremy R.; Pontvianne, Frederic

Using affinity purification and mass spectrometry, we identified the subunits of Arabidopsis thaliana multisubunit RNA Polymerases I and III (abbreviated as Pol I and Pol III), providing the first description of their physical compositions in plants. AC40 and AC19 subunits are typically common to Pol I (a.k.a. Pol A) and Pol III (a.k.a. Pol C) and are encoded by single genes whose mutation, in humans, is a cause of the craniofacial disorder, Treacher-Collins Syndrome. Surprisingly, A. thaliana, and related species, express two distinct AC40 paralogs, one of which assembles into Pol I and the other of which assembles into Polmore » III. Changes at eight amino acid positions correlate with this functional divergence of Pol I and Pol III-specific AC40 paralogs. Two genes encode homologs of the yeast C53 subunit, and either variant can assemble into Pol III. By contrast, only one of two potential C17 variants, and one of two potential C31 variants were detected in Pol III. We introduce a new nomenclature system for plant Pol I and Pol III subunits in which the twelve subunits that are structurally and functionally homologous among Pols I through V are assigned equivalent numbers.« less

Umsetzung der Unternehmensstrategie mit der Balanced Scorecard

NASA Astrophysics Data System (ADS)

Crespo, Isabel; Bergmann, Lars; Portmann, Stefan; Lacker, Thomas; Lacker, Michael; Fleischmann, Jürgen; Kozó, Hans

Die Balanced Scorecard (BSC) ist ein Ansatz zum strategischen Management, der neben der Ausrichtung des Unternehmens auf finanzielle Zielwerte ebenso großes Gewicht auf so genannte weiche Faktoren legt, die den wirtschaftlichen Erfolg eines Unternehmens erst ermöglichen. Das entscheidende Merkmal der Balanced Scorecard ist dabei, dass sie ein ausgewogenes System strategischer Ziele herstellt, welches das Unternehmen hinsichtlich der vier Perspektiven Finanzen, Kunden, interne Prozesse und Mitarbeiter und Potenziale strategisch ausrichtet (Kaplan u. Norton 1997).

Uniform Free-Energy Profiles of the P-O Bond Formation and Cleavage Reactions Catalyzed by DNA Polymerases β and λ.

PubMed

Klvaňa, Martin; Bren, Urban; Florián, Jan

2016-12-29

Human X-family DNA polymerases β (Polβ) and λ (Polλ) catalyze the nucleotidyl-transfer reaction in the base excision repair pathway of the cellular DNA damage response. Using empirical valence bond and free-energy perturbation simulations, we explore the feasibility of various mechanisms for the deprotonation of the 3'-OH group of the primer DNA strand, and the subsequent formation and cleavage of P-O bonds in four Polβ, two truncated Polλ (tPolλ), and two tPolλ Loop1 mutant (tPolλΔL1) systems differing in the initial X-ray crystal structure and nascent base pair. The average calculated activation free energies of 14, 18, and 22 kcal mol -1 for Polβ, tPolλ, and tPolλΔL1, respectively, reproduce the trend in the observed catalytic rate constants. The most feasible reaction pathway consists of two successive steps: specific base (SB) proton transfer followed by rate-limiting concerted formation and cleavage of the P-O bonds. We identify linear free-energy relationships (LFERs) which show that the differences in the overall activation and reaction free energies among the eight studied systems are determined by the reaction free energy of the SB proton transfer. We discuss the implications of the LFERs and suggest pK a of the 3'-OH group as a predictor of the catalytic rate of X-family DNA polymerases.

Uniform Free-Energy Profiles of the P–O Bond Formation and Cleavage Reactions Catalyzed by DNA Polymerases β and λ

PubMed Central

2016-01-01

Human X-family DNA polymerases β (Polβ) and λ (Polλ) catalyze the nucleotidyl-transfer reaction in the base excision repair pathway of the cellular DNA damage response. Using empirical valence bond and free-energy perturbation simulations, we explore the feasibility of various mechanisms for the deprotonation of the 3′-OH group of the primer DNA strand, and the subsequent formation and cleavage of P–O bonds in four Polβ, two truncated Polλ (tPolλ), and two tPolλ Loop1 mutant (tPolλΔL1) systems differing in the initial X-ray crystal structure and nascent base pair. The average calculated activation free energies of 14, 18, and 22 kcal mol–1 for Polβ, tPolλ, and tPolλΔL1, respectively, reproduce the trend in the observed catalytic rate constants. The most feasible reaction pathway consists of two successive steps: specific base (SB) proton transfer followed by rate-limiting concerted formation and cleavage of the P–O bonds. We identify linear free-energy relationships (LFERs) which show that the differences in the overall activation and reaction free energies among the eight studied systems are determined by the reaction free energy of the SB proton transfer. We discuss the implications of the LFERs and suggest pKa of the 3′-OH group as a predictor of the catalytic rate of X-family DNA polymerases. PMID:27992186

Integriertes Informationsmanagement an der Westfälischen Wilhelms-Universität Münster - Das Projekt MIRO

NASA Astrophysics Data System (ADS)

Vogl, Raimund; Gildhorn, Antje; Labitzke, Jörg; Wibberg, Michael

An der Westfälischen Wilhelms-Universität Münster (WWU) wurde bereits 1996 ein tragfähiges, kooperativ ausgerichtetes System der IT-Governance im Zusammenspiel zentraler und dezentraler IT-Leistungserbringer etabliert. Um den Anforderungen an ein integriertes Informationsmanagement im Überlappungsfeld von Information, Kommunikation und Medien (IKM) durch das Zusammenspiel der zentralen Einrichtungen Universitätsverwaltung (UniV), Universitäts- und Landesbibliothek (ULB) und Zentrum für Informationsverarbeitung (ZIV) gerecht zu werden, wurde 2003 der IKM-Service institutionalisiert. In diesem Rahmen wurde das Projekt Münster Information System for Research and Organization (MIRO) entwickelt, das als Leistungszentrum für Forschungsinformation von der DFG gefördert wird. Die bisherigen Projekterfahrungen, erreichten Ziele und verbleibenden Aufgaben werden dargestellt. Im Projektverlauf haben sich insbesondere die etablierten IT-Governance und Versorgungs-Strukturen sowie die Unterstützung der Hochschulleitung als essentielle Erfolgskriterien erwiesen.

Distributed Energy Systems: Security Implications of the Grid of the Future

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

Stamber, Kevin L.; Kelic, Andjelka; Taylor, Robert A.

2017-01-01

Distributed Energy Resources (DER) are being added to the nation's electric grid, and as penetration of these resources increases, they have the potential to displace or offset large-scale, capital-intensive, centralized generation. Integration of DER into operation of the traditional electric grid requires automated operational control and communication of DER elements, from system measurement to control hardware and software, in conjunction with a utility's existing automated and human-directed control of other portions of the system. Implementation of DER technologies suggests a number of gaps from both a security and a policy perspective. This page intentionally left blank.

Stufenweise Integration von eLearning an der Technischen Universität München

NASA Astrophysics Data System (ADS)

Pätzold, Sebastian; Graf, Stephan; Gergintchev, Ivan; Pongratz, Hans; Rathmayer, Sabine

Der vorliegende Beitrag beschreibt als Best Practice Beispiel die stufenweise Integration eines Learning Management Systems (LMS) in die Infrastruktur von Information und Kommunikation (IuK) der Technischen Universität München (TUM). Dabei wird sowohl die Konsolidierung mehrfach angebotener Funktionalitäten und Dienste in den verschiedenen Portalen der Universität als auch die sukzessive Optimierung der Abläufe aufgezeigt. Gleichzeitig wird auf zukünftige weitere Entwicklungen hin zu einer vollständigen Integration der IuK, aber auch auf die Probleme in den unterschiedlichen Stadien der Entwicklung eingegangen.

DMS Advanced Applications for Accommodating High Penetrations of DERs and Microgrids: Preprint

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

Pratt, Annabelle; Veda, Santosh; Maitra, Arindam

Efficient and effective management of the electrical distribution system requires an integrated system approach for Distribution Management Systems (DMS), Distributed Energy Resources (DERs), Distributed Energy Resources Management System (DERMS), and microgrids to work in harmony. This paper highlights some of the outcomes from a U.S. Department of Energy (DOE), Office of Electricity (OE) project, including 1) Architecture of these integrated systems, and 2) Expanded functions of two example DMS applications, Volt-VAR optimization (VVO) and Fault Location, Isolation and Service Restoration (FLISR), to accommodate DER. For these two example applications, the relevant DER Group Functions necessary to support communication between DMSmore » and Microgrid Controller (MC) in grid-tied mode are identified.« less

DMS Advanced Applications for Accommodating High Penetrations of DERs and Microgrids

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

Pratt, Annabelle; Veda, Santosh; Maitra, Arindam

Efficient and effective management of the electric distribution system requires an integrated approach to allow various systems to work in harmony, including distribution management systems (DMS), distributed energy resources (DERs), distributed energy resources management systems, and microgrids. This study highlights some outcomes from a recent project sponsored by the US Department of Energy, Office of Electricity Delivery and Energy Reliability, including information about (i) the architecture of these integrated systems and (ii) expanded functions of two example DMS applications to accommodate DERs: volt-var optimisation and fault location, isolation, and service restoration. In addition, the relevant DER group functions necessary tomore » support communications between the DMS and a microgrid controller in grid-tied mode are identified.« less

Advanced Communication and Control Solutions of Distributed Energy Resources (DER)

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

Asgeirsson, Haukur; Seguin, Richard; Sherding, Cameron

2007-01-10

This report covers work performed in Phase II of a two phase project whose objective was to demonstrate the aggregation of multiple Distributed Energy Resources (DERs) and to offer them into the energy market. The Phase I work (DE-FC36-03CH11161) created an integrated, but distributed, system and procedures to monitor and control multiple DERs from numerous manufacturers connected to the electric distribution system. Procedures were created which protect the distribution network and personnel that may be working on the network. Using the web as the communication medium for control and monitoring of the DERs, the integration of information and security wasmore » accomplished through the use of industry standard protocols such as secure SSL,VPN and ICCP. The primary objective of Phase II was to develop the procedures for marketing the power of the Phase I aggregated DERs in the energy market, increase the number of DER units, and implement the marketing procedures (interface with ISOs) for the DER generated power. The team partnered with the Midwest Independent System Operator (MISO), the local ISO, to address the energy market and demonstrate the economic dispatch of DERs in response to market signals. The selection of standards-based communication technologies offers the ability of the system to be deployed and integrated with other utilities’ resources. With the use of a data historian technology to facilitate the aggregation, the developed algorithms and procedures can be verified, audited, and modified. The team has demonstrated monitoring and control of multiple DERs as outlined in phase I report including procedures to perform these operations in a secure and safe manner. In Phase II, additional DER units were added. We also expanded on our phase I work to enhance communication security and to develop the market model of having DERs, both customer and utility owned, participate in the energy market. We are proposing a two-part DER energy market model--a utility need business model and an independent energy aggregator-business model. The approach of developing two group models of DER energy participation in the market is unique. The Detroit Edison (DECo, Utility)-led team includes: DTE Energy Technologies (Dtech, DER provider), Electrical Distribution Design (EDD, Virginia Tech company supporting EPRI’s Distribution Engineering Workstation, DEW), Systems Integration Specialists Company (SISCO, economic scheduling and real-time protocol integrator), and OSIsoft (PI software system for managing real-time information). This team is focused on developing the application engineering, including software systems necessary for DER’s integration, control and sale into the market place. Phase II Highlights Installed and tested an ICCP link with SSL (security) between DECo, the utility, and DTE Energy Technologies (DTECH), the aggregator, making DER data available to the utility for both monitoring and control. Installed and tested PI process book with circuit & DER operational models for DECo SOC/ROC operator’s use for monitoring of both utility circuit and customer DER parameters. The PI Process Book models also included DER control for the DECo SOC/ROC operators, which was tested and demonstrated control. The DER Tagging and Operating Procedures were developed, which allowed that control to be done in a safe manner, were modified for required MOC/MISO notification procedures. The Distribution Engineering Workstation (DEW) was modified to include temperature normalized load research statistics, using a 30 hour day-ahead weather feed. This allowed day-ahead forecasting of the customer load profile and the entire circuit to determine overload and low voltage problems. This forecast at the point of common coupling was passed to DTech DR SOC for use in their economic dispatch algorithm. Standard Work Instructions were developed for DER notification, sale, and operation into the MISO market. A software mechanism consisting of a suite of new and revised functionality was developed that integrated with the local ISO such that offers can be made electronically without human intervention. A suite of software was developed by DR SOC enabling DER usage in real time and day-ahead: Generation information file exchange with PI and the utility power flow A utility day-ahead information file Energy Offer Web Service Market Result Web Service Real-Time Meter Data Web Service Real-Time Notification Web Service Registered over 20 DER with MISO in Demand Response Market and demonstrated electronic sale to MISO.« less

Phänomenologische Grundlagen der Wärmelehre

NASA Astrophysics Data System (ADS)

Heintze, Joachim

Die Physik der Wärme lässt sich auf zweierlei Weise formulieren: Einmal als Mechanik eines Systems, das eine enorm große Zahl von Teilchen enthält (statistische Mechanik), und einmal mit Hilfe von ad hoc eingeführten Größen, den sogenannten Zustandsgrößen, die geeignet sind, das Verhalten eines solchen Systems zu beschreiben, ohne dass man die Teilchen selbst und ihre Bewegungen betrachten muss (Thermodynamik). Wir werden beide Ansätze in ihrer einfachsten und anschaulichsten Ausprägung in Kap. 5 (kinetische Gastheorie) bzw. in Kap. 8 (Grundbegriffe der Thermodynamik) behandeln. Obgleich sich die volle Durchführung des Programms als begrifflich und mathematisch recht schwierig erweist - die Vorlesung "Thermodynamik und Statistik" steht gewöhnlich am Ende der Kursvorlesungen über theoretische Physik - werden wir doch auf der Grundlage der Kap. 5 und 8 eine Menge über die Physik der Wärme lernen können. Den Ausgangspunkt der Wärmelehre bilden jedoch allemal die Naturerscheinungen, die wir hier in Kap. 4 behandeln wollen: Wärme, Kälte, Temperaturausgleich. Wir werden untersuchen, wie man diese Begriffe quantifizieren kann, und was bei der Erwärmung oder Abkühlung eines Körpers vor sich geht. Dabei werden wir auf den I. und II. Hauptsatz der Wärmelehre stoßen.

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

Thomas, H. P.; Basso, T. S.; Kroposki, B.

The Department of Energy (DOE) Distributed Power Program (DPP) is conducting work to complete, validate in the field, and support the development of a national interconnection standard for distributed energy resources (DER), and to address the institutional and regulatory barriers slowing the commercial adoption of DER systems. This work includes support for the IEEE standards, including P1547 Standard for Interconnecting Distributed Resources with Electric Power Systems, P1589 Standard for Conformance Test Procedures for Equipment Interconnecting Distributed Resources with Electric Power Systems, and the P1608 Application Guide. Work is also in progress on system integration research and development (R&D) on themore » interface and control of DER with local energy systems. Additional efforts are supporting high-reliability power for industry, evaluating innovative concepts for DER applications, and exploring plug-and-play interface and control technologies for intelligent autonomous interconnection systems. This paper summarizes (1) the current status of the IEEE interconnection standards and application guides in support of DER, and (2) the R&D in progress at the National Renewable Energy Laboratory (NREL) for interconnection and system integration and application of distributed energy resources.« less

Isotrope und homogene Materie - Kosmen; On Dynamics and Thermodynamics of Isotropic Matter-Universes

NASA Astrophysics Data System (ADS)

Treder, H.-J.

Die Dynamik und Thermodynamik großer kosmischer Systeme ist fast unabhängig von den besonderen Theorien über die Gravitation. Nur die Feinstruktur der Kosmologie und Kosmonogie reflektiert die speziellen Hypothesen. Diese Neutralität gegenüber den konkreten Gravodynamiken ist die Konsequenz der fundamentalen Eigenschaften der Gravitation: Der Prinzipien der Äquivalenz von Trägheit und Schwere. The dynamics and thermodynamics of great cosmical systems are nearly independent of the theory of gravitation and only the fine-structure of cosmogony and cosmology reflects the special hypotheses.The neutrality against the concret gravodynamics is a consequence of the fundamental properties of gravitation: the principlies of equivalence of gravity and inertia.

Synchronization and Random Triggering of Lymphatic Vessel Contractions

PubMed Central

Baish, James W.; Kunert, Christian; Padera, Timothy P.; Munn, Lance L.

2016-01-01

The lymphatic system is responsible for transporting interstitial fluid back to the bloodstream, but unlike the cardiovascular system, lacks a centralized pump-the heart–to drive flow. Instead, each collecting lymphatic vessel can individually contract and dilate producing unidirectional flow enforced by intraluminal check valves. Due to the large number and spatial distribution of such pumps, high-level coordination would be unwieldy. This leads to the question of how each segment of lymphatic vessel responds to local signals that can contribute to the coordination of pumping on a network basis. Beginning with elementary fluid mechanics and known cellular behaviors, we show that two complementary oscillators emerge from i) mechanical stretch with calcium ion transport and ii) fluid shear stress induced nitric oxide production (NO). Using numerical simulation and linear stability analysis we show that the newly identified shear-NO oscillator shares similarities with the well-known Van der Pol oscillator, but has unique characteristics. Depending on the operating conditions, the shear-NO process may i) be inherently stable, ii) oscillate spontaneously in response to random disturbances or iii) synchronize with weak periodic stimuli. When the complementary shear-driven and stretch-driven oscillators interact, either may dominate, producing a rich family of behaviors similar to those observed in vivo. PMID:27935958

Synchronization and Random Triggering of Lymphatic Vessel Contractions.

PubMed

Baish, James W; Kunert, Christian; Padera, Timothy P; Munn, Lance L

2016-12-01

The lymphatic system is responsible for transporting interstitial fluid back to the bloodstream, but unlike the cardiovascular system, lacks a centralized pump-the heart-to drive flow. Instead, each collecting lymphatic vessel can individually contract and dilate producing unidirectional flow enforced by intraluminal check valves. Due to the large number and spatial distribution of such pumps, high-level coordination would be unwieldy. This leads to the question of how each segment of lymphatic vessel responds to local signals that can contribute to the coordination of pumping on a network basis. Beginning with elementary fluid mechanics and known cellular behaviors, we show that two complementary oscillators emerge from i) mechanical stretch with calcium ion transport and ii) fluid shear stress induced nitric oxide production (NO). Using numerical simulation and linear stability analysis we show that the newly identified shear-NO oscillator shares similarities with the well-known Van der Pol oscillator, but has unique characteristics. Depending on the operating conditions, the shear-NO process may i) be inherently stable, ii) oscillate spontaneously in response to random disturbances or iii) synchronize with weak periodic stimuli. When the complementary shear-driven and stretch-driven oscillators interact, either may dominate, producing a rich family of behaviors similar to those observed in vivo.

Using non-linear analogue of Nyquist diagrams for analysis of the equation describing the hemodynamics in blood vessels near pathologies

NASA Astrophysics Data System (ADS)

Cherevko, A. A.; Bord, E. E.; Khe, A. K.; Panarin, V. A.; Orlov, K. J.; Chupakhin, A. P.

2016-06-01

This article considers method of describing the behaviour of hemodynamic parameters near vascular pathologies. We study the influence of arterial aneurysms and arteriovenous malformations on the vascular system. The proposed method involves using generalized model of Van der Pol-Duffing to find out the characteristic behaviour of blood flow parameters. These parameters are blood velocity and pressure in the vessel. The velocity and pressure are obtained during the neurosurgery measurements. It is noted that substituting velocity on the right side of the equation gives good pressure approximation. Thus, the model reproduces clinical data well enough. In regard to the right side of the equation, it means external impact on the system. The harmonic functions with various frequencies and amplitudes are substituted on the right side of the equation to investigate its properties. Besides, variation of the right side parameters provides additional information about pressure. Non-linear analogue of Nyquist diagrams is used to find out how the properties of solution depend on the parameter values. We have analysed 60 cases with aneurysms and 14 cases with arteriovenous malformations. It is shown that the diagrams are divided into classes. Also, the classes are replaced by another one in the definite order with increasing of the right side amplitude.

Analysis of structural patterns in the brain with the complex network approach

NASA Astrophysics Data System (ADS)

Maksimenko, Vladimir A.; Makarov, Vladimir V.; Kharchenko, Alexander A.; Pavlov, Alexey N.; Khramova, Marina V.; Koronovskii, Alexey A.; Hramov, Alexander E.

2015-03-01

In this paper we study mechanisms of the phase synchronization in a model network of Van der Pol oscillators and in the neural network of the brain by consideration of macroscopic parameters of these networks. As the macroscopic characteristics of the model network we consider a summary signal produced by oscillators. Similar to the model simulations, we study EEG signals reflecting the macroscopic dynamics of neural network. We show that the appearance of the phase synchronization leads to an increased peak in the wavelet spectrum related to the dynamics of synchronized oscillators. The observed correlation between the phase relations of individual elements and the macroscopic characteristics of the whole network provides a way to detect phase synchronization in the neural networks in the cases of normal and pathological activity.

Smartes System für die Energiewende - der Übertragungsnetzbetreiber in der digitalen Zukunft

NASA Astrophysics Data System (ADS)

Pflaum, Rainer; Egeler, Tobias

Die Übertragungsnetze stellen eine zuverlässige Versorgung von Haushalt, Gewerbe und Industrie mit elektrischer Energie sicher und sind damit Grundlage einer modernen Wirtschaft und Gesellschaft. Die mittlerweile unumkehrbaren Entwicklungen der nationalen und europäischen Energiewende stellen den Übertragungsnetzbetreiber in seinen Kernaufgaben, dem Bau und Betrieb von Netzen, dem Markt- und Netzzugang und der Integration der erneuerbaren Energien vor neue und große Herausforderungen. Verbrauchsnahe dezentrale Erzeugung wie verbrauchsferne zentrale Erzeugung muss im Sinne der Gewährleistung der Systemstabilität gemanagt und in Einklang mit dem Verbrauch gebracht werden. Erneuerbare Energien müssen zudem in einem solchen System ihren Beitrag zur System- und Marktintegration leisten. All das erfordert mehr Daten, um in einem Gesamtsystem dynamische Reaktionsmöglichkeiten gewährleisten zu können. Erst die "Digitalisierung" schafft dabei die notwendigen Voraussetzungen die Komplexität zu stemmen. Die Digitalisierung stellt daher ein Kernelement dieses Wandels des Übertragungsnetzbetreibers dar, die einerseits mit zum Entstehen der neuen Herausforderungen beiträgt, andererseits aber auch hilft Werkzeuge bereitzustellen, diesen Herausforderungen zu begegnen. Im folgenden Beitrag wird aufgezeigt, wie die Digitalisierung die Aufgaben und Instrumente des Übertragungsnetzbetreibers verändern. Ausgehend von den heutigen Aufgaben eines Übertragungsnetzbetreibers und dem gültigen Rechtsrahmen werden unter dem Begriff "Notwendiges Set für morgen" smarte Elemente und Werkzeuge beschrieben, die bereits heute im Einsatz sind oder in den nächsten Jahren notwendig werden. Im Anschluss erfolgt anhand einiger Beispiele aus unterschiedlichen Bereichen eine Konkretisierung der Einsatzzwecke der Digitalisierung beim Übertragungsnetzbetreiber. Ein kurzer Ausblick mit Fokus auf den weiteren Veränderungsprozess rundet den Beitrag ab.

Scaling laws for van der Waals interactions in nanostructured materials.

PubMed

Gobre, Vivekanand V; Tkatchenko, Alexandre

2013-01-01

Van der Waals interactions have a fundamental role in biology, physics and chemistry, in particular in the self-assembly and the ensuing function of nanostructured materials. Here we utilize an efficient microscopic method to demonstrate that van der Waals interactions in nanomaterials act at distances greater than typically assumed, and can be characterized by different scaling laws depending on the dimensionality and size of the system. Specifically, we study the behaviour of van der Waals interactions in single-layer and multilayer graphene, fullerenes of varying size, single-wall carbon nanotubes and graphene nanoribbons. As a function of nanostructure size, the van der Waals coefficients follow unusual trends for all of the considered systems, and deviate significantly from the conventionally employed pairwise-additive picture. We propose that the peculiar van der Waals interactions in nanostructured materials could be exploited to control their self-assembly.

Herausforderungen durch die deutsche Wiedervereinigung

NASA Astrophysics Data System (ADS)

Stäglin, Reiner

Die Wiedervereinigung stellte auch die Statistik vor große Aufgaben. Die als Organ der staatlichen Planung staatsnah orientierte Statistik der DDR musste auf das zur Neutralität und wissenschaftlichen Unabhängigkeit verpflichtete System der Bundesrepublik umgestellt werden. Ebenso verlangten die Universitäten eine Neuorientierung. Die Deutsche Statistische Gesellschaft hat sich vor allem dreier Aufgaben mit großem Engagement, aber auch mit Bedachtsamkeit angenommen: Aufnahme und Integration der Statistiker aus den neuen Bundesländern in die Gesellschaft, Begleitung der Neuausrichtung des Faches Statistik an deren Hochschulen und Sicherung sowie Nutzung von Datenbeständen der ehemaligen DDR.

Distinct Mechanisms of Transcription Initiation by RNA Polymerases I and II.

PubMed

Engel, Christoph; Neyer, Simon; Cramer, Patrick

2018-05-20

RNA polymerases I and II (Pol I and Pol II) are the eukaryotic enzymes that catalyze DNA-dependent synthesis of ribosomal RNA and messenger RNA, respectively. Recent work shows that the transcribing forms of both enzymes are similar and the fundamental mechanisms of RNA chain elongation are conserved. However, the mechanisms of transcription initiation and its regulation differ between Pol I and Pol II. Recent structural studies of Pol I complexes with transcription initiation factors provided insights into how the polymerase recognizes its specific promoter DNA, how it may open DNA, and how initiation may be regulated. Comparison with the well-studied Pol II initiation system reveals a distinct architecture of the initiation complex and visualizes promoter- and gene-class-specific aspects of transcription initiation. On the basis of new structural studies, we derive a model of the Pol I transcription cycle and provide a molecular movie of Pol I transcription that can be used for teaching.

Improvement of SPM nonlinear limit by chirped duobinary PolSK transmission

NASA Astrophysics Data System (ADS)

Yang, Lixiu; Fan, Jiayu; Wang, Lutang; Huang, Zhaoming

2005-02-01

In today's terrestrial long-haul optical fiber communication systems, high channel powers are required to obtain a large transmission distance with reasonable optical amplifier spacing. In such systems, however, the presence of nonlinear effects such as the self-phase modulation (SPM) and the fiber dispersion as well as their combined effects, called SPM-induced nonlinear limitation or SPM limit, will seriously degrade the system performances in respect of the effective transmission distance and ultimately become a limiting factor in high-speed, long-haul optical fiber transmission.In this paper, a new transmission format: chirped duobinary PolSK transmission, has been proposed to generate a pre-chirped duobianry signal with fixed polarity (either positive or negative), which is modulated by a PolSK modulator. This format is based on a transmitter setup consisting of a duobinary PolSK Modulation transmitter followed by an additional phase modulator. The chirped duobinary PolSK transmission reduces the signal degradation and spectral broadening in the nonlinear regime significantly. Thus it shifts this SPM nonlinear limit to enable more relaxed dispersion compensation at high optical power compared to the conventional duobinary schemes.The simulation results show chirped duobinary PolSK transmission enlarges the dispersion limited transmission distance, increases the dispersion tolerance and overcome the SPM nonlinear limit.

Foundational Report Series: Advanced Distribution Management Systems for Grid Modernization, DMS Integration of Distributed Energy Resources and Microgrids

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

Singh, Ravindra; Reilly, James T.; Wang, Jianhui

Deregulation of the electric utility industry, environmental concerns associated with traditional fossil fuel-based power plants, volatility of electric energy costs, Federal and State regulatory support of “green” energy, and rapid technological developments all support the growth of Distributed Energy Resources (DERs) in electric utility systems and ensure an important role for DERs in the smart grid and other aspects of modern utilities. DERs include distributed generation (DG) systems, such as renewables; controllable loads (also known as demand response); and energy storage systems. This report describes the role of aggregators of DERs in providing optimal services to distribution networks, through DERmore » monitoring and control systems—collectively referred to as a Distributed Energy Resource Management System (DERMS)—and microgrids in various configurations.« less

Assimilation of Dual-Polarimetric Radar Observations with WRF GSI

NASA Technical Reports Server (NTRS)

Li, Xuanli; Mecikalski, John; Fehnel, Traci; Zavodsky, Bradley; Srikishen, Jayanthi

2014-01-01

Dual-polarimetric (dual-pol) radar typically transmits both horizontally and vertically polarized radio wave pulses. From the two different reflected power returns, more accurate estimate of liquid and solid cloud and precipitation can be provided. The upgrade of the traditional NWS WSR-88D radar to include dual-pol capabilities will soon be completed for the entire NEXRAD network. Therefore, the use of dual-pol radar network will have a broad impact in both research and operational communities. The assimilation of dual-pol radar data is especially challenging as few guidelines have been provided by previous research. It is our goal to examine how to best use dual-pol radar data to improve forecast of severe storm and forecast initialization. In recent years, the Development Testbed Center (DTC) has released the community Gridpoint Statistical Interpolation (GSI) DA system for the Weather Research and Forecasting (WRF) model. The community GSI system runs in independently environment, yet works functionally equivalent to operational centers. With collaboration with the NASA Short-term Prediction Research and Transition (SPoRT) Center, this study explores regional assimilation of the dual-pol radar variables from the WSR-88D radars for real case storms. Our presentation will highlight our recent effort on incorporating the horizontal reflectivity (ZH), differential reflectivity (ZDR), specific differential phase (KDP), and radial velocity (VR) data for initializing convective storms, with a significant focus being on an improved representation of hydrometeor fields. In addition, discussion will be provided on the development of enhanced assimilation procedures in the GSI system with respect to dual-pol variables. Beyond the dual-pol variable assimilation procedure developing within a GSI framework, highresolution (=1 km) WRF model simulations and storm scale data assimilation experiments will be examined, emphasizing both model initialization and short-term forecast of precipitation fields and processes. Further details of the methodology of data assimilation, the impact of different dual-pol variables, the influence on precipitation forecast will be presented at the conference.

Der II. Hauptsatz der Wärmelehre

NASA Astrophysics Data System (ADS)

Heintze, Joachim

Wir haben in (4.44) den II. Hauptsatz als empirische Tatsache folgendermaßen formuliert: (i) Wärmeenergie geht von selbst nur von einem wärmeren Körper auf einen kälteren über, niemals in der umgekehrten Richtung. Nun werden wir beweisen, dass sich aus diesem Prinzip folgende äquivalente Formulierungen für den II. Hauptsatz ableiten lassen: (ii) Es ist unmöglich, ein Perpetuum mobile zweiter Art zu bauen, d. h. eine Maschine, die fortlaufend Wärmeenergie vollständig in mechanische Arbeit umsetzen kann. Eine Wärmekraftmaschine, die einen Kreisprozess mit der höchsten Temperatur Tw und der niedrigsten Temperatur Tk durchläuft, hat höchstens den Carnotschen Wirkungsgrad c = (Tw - Tk)/Tw. Wenn in der Maschine nur reversible Prozesse ablaufen, die gesamte Wärmezufuhr bei der Temperatur Tw erfolgt und ausschließlich bei der Temperatur Tw gekühlt wird, ist ihr Wirkungsgrad = C. Es gibt keine Wärmekraftmaschine, die eine bessere Ausnutzung der Wärmeenergie ermöglicht. (iv) In jedem thermodynamischen System existiert die Zustandsgröße Entropie, definiert durch ihr Differential dS = (dQrev)/T . Entropie kann erzeugt, aber nicht vernichtet werden. Bei Zustandsänderungen, die in einem abgeschlossenen System ablaufen, nimmt die Entropie entweder zu (irreversible Prozesse), oder sie bleibt konstant (reversible Prozesse). Im Anschluss an (iii) werden wir zur Definition der thermodynamischen Temperatur und bei der Diskussion von (iv) zu einem tieferen Verständnis der Entropie gelangen. Es zeigt sich, dass die Entropie das eigentliche Bindeglied zwischen Mechanik und Wärmelehre darstellt. Am Ende des Kapitels werden wir einige Anwendungen des II. Hauptsatzes betrachten.

Joint Seismic-Geodetic Algorithm for Finite-Fault Detection and Slip Inversion in the West Coast ShakeAlert System

NASA Astrophysics Data System (ADS)

Smith, D. E.; Felizardo, C.; Minson, S. E.; Boese, M.; Langbein, J. O.; Murray, J. R.

2016-12-01

Finite-fault source algorithms can greatly benefit earthquake early warning (EEW) systems. Estimates of finite-fault parameters provide spatial information, which can significantly improve real-time shaking calculations and help with disaster response. In this project, we have focused on integrating a finite-fault seismic-geodetic algorithm into the West Coast ShakeAlert framework. The seismic part is FinDer 2, a C++ version of the algorithm developed by Böse et al. (2012). It interpolates peak ground accelerations and calculates the best fault length and strike from template matching. The geodetic part is a C++ version of BEFORES, the algorithm developed by Minson et al. (2014) that uses a Bayesian methodology to search for the most probable slip distribution on a fault of unknown orientation. Ultimately, these two will be used together where FinDer generates a Bayesian prior for BEFORES via the methodology of Minson et al. (2015), and the joint solution will generate estimates of finite-fault extent, strike, dip, best slip distribution, and magnitude. We have created C++ versions of both FinDer and BEFORES using open source libraries and have developed a C++ Application Protocol Interface (API) for them both. Their APIs allow FinDer and BEFORES to contribute to the ShakeAlert system via an open source messaging system, ActiveMQ. FinDer has been receiving real-time data, detecting earthquakes, and reporting messages on the development system for several months. We are also testing FinDer extensively with Earthworm tankplayer files. BEFORES has been tested with ActiveMQ messaging in the ShakeAlert framework, and works off a FinDer trigger. We are finishing the FinDer-BEFORES connections in this framework, and testing this system via seismic-geodetic tankplayer files. This will include actual and simulated data.

Erzwingt die Quantenmechanik eine drastische Änderung unseres Weltbilds? Gedanken und Experimente nach Einstein, Podolsky und Rosen

NASA Astrophysics Data System (ADS)

Frodl, Peter

Von den Anfängen der Quantenmechanik bis heute gibt es Versuche, sie als statistische Theorie über Ensembles individueller klassischer Systeme zu interpretieren. Die Bedingungen, unter denen Theorien verborgener Parameter zu deterministischen Beschreibungen dieser individuellen Systeme als klassisch angesehen werden können, wurden von Einstein, Podolsky und Rosen 1935 formuliert: 1. Physikalische Systeme sind im Prinzip separierbar. 2. Zu jeder physikalischen Größe, deren Wert man ohne Störung des betrachteten Systems mit Sicherheit voraussagen kann, existiert ein ihr entsprechendes Element der physikalischen Realität.Zusammen sind sie, wie Bell 1964 gezeigt hat, prinzipiell unverträglich mit der Quantenmechanik und unhaltbar angesichts neuerer Experimente. Diese erweisen einmal mehr die Quantenmechanik als richtige Theorie. Um ihre Ergebnisse zu verstehen, müssen wir entweder die in der klassischen Physik als selbstverständlich angesehene Annahme der Separierbarkeit physikalischer Systeme aufgeben oder unseren Begriff der physikalischen Realität revidieren. Eine Untersuchung des Begriffs der Separabilität und einige Überlegungen zum Problem der Messung von Observablen zeigen, daß eine Änderung des Begriffs der physikalischen Realität unumgänglich ist. Der revidierte Realitätsbegriff sollte mit klassischer Physik und Quantenmechanik verträglich sein, um ein einheitliches Weltbild zu ermöglichen.Translated AbstractDo Quantum Mechanics Force us to Drastically Change our View of the World? Thoughts and Experiments after Einstein, Podolsky and RosenSince the advent of quantum mechanics there have been attempts of its interpretation in terms of statistical theory concerning individual classical systems. The very conditions necessary to consider hidden variable theories describing these individual systems as classical had been pointed out by Einstein, Podolsky and Rosen in 1935: 1. Physical systems are in principle separable. 2. If it is possible to predict with certainty the value of a physical quantity without disturbing the system under consideration, then there exists an element of physical reality corresponding to this physical quantity.Together they are, as was shown by Bell in 1964, incompatible in principle with quantum mechanics and no more tenable in view of recent experiments. These experiments once more corroborate quantum theory. In order to understand their results we are forced either to drop the assumption of separability of physical systems (taken for self-evident in classical physics) or to change our concept of physical reality. After investigating the notion of separability and connecting the EPR-correlations to the measurement problem we, conclude that a change of the concept of physical reality is indispensable. The revised concept should be compatible with both classical and quantum physics in order to allow a uniform view of the physical world.

Dynamics of Relaxation Processes of Spontaneous Otoacoustic Emissions

NASA Astrophysics Data System (ADS)

Murphy, William James

The dynamical response of spontaneous otoacoustic emissions (SOAEs) to suppression by ipsilateral pulsed external tones of different frequencies and levels is investigated in nine female subjects under normal conditions and in four female subjects during periods when aspirin is being administered. A simple Van der Pol limit-cycle oscillator driven by an external tone is used as an interpretive model. Typical results for both the onset of, and recovery from suppression yield 1/r_1 (where -r_1 is the negative linear component of the damping function) in the range of 2-25 msec. In accordance with the predictions of the model: (a) the relaxation time for the onset of suppression increases with the amount of suppression induced by the external tone, (b) the values of r _1 and the amplitudes of the unsuppressed emissions exhibit an inverse correlation, (c) the values inferred for r_1 are not significantly dependent on the frequency of the pulsed suppressor tone and (d) the inferred r_1 values are not significantly dependent upon the amount of suppression. In investigations involving subjects under aspirin administration, the changes in the relaxation time constants indicate that the main effect of aspirin administration is to reduce the negative damping parameter r_1. The salicylate is apparently not metabolized in some subjects whose emissions are negligibly affected by aspirin administration. A modification of the single-oscillator model is used to describe pulsed suppression data obtained from a primary SOAE (2545 Hz) which is suppressed by a neighboring secondary emission (2895 Hz). The response of the SOAE amplitude during pulsed suppression is modeled by a pair of Van der Pol limit-cycle oscillators with the primary oscillator linearly coupled to the displacement of the secondary higher-frequency one. The relaxation time constants for the onset of, and recovery from, suppression are 4.5 and 4.8 msec, respectively, for the primary SOAE and 7.5 and 10.5 msec for the secondary one. Aspirin administration reduces the magnitude of the overshoot by reducing the level of the higher frequency SOAE and thereby eliminating the suppression of the lower frequency one.

Assessment of Distributed Generation Potential in JapaneseBuildings

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

Zhou, Nan; Marnay, Chris; Firestone, Ryan

2005-05-25

To meet growing energy demands, energy efficiency, renewable energy, and on-site generation coupled with effective utilization of exhaust heat will all be required. Additional benefit can be achieved by integrating these distributed technologies into distributed energy resource (DER) systems (or microgrids). This research investigates a method of choosing economically optimal DER, expanding on prior studies at the Berkeley Lab using the DER design optimization program, the Distributed Energy Resources Customer Adoption Model (DER-CAM). DER-CAM finds the optimal combination of installed equipment from available DER technologies, given prevailing utility tariffs, site electrical and thermal loads, and a menu of available equipment.more » It provides a global optimization, albeit idealized, that shows how the site energy loads can be served at minimum cost by selection and operation of on-site generation, heat recovery, and cooling. Five prototype Japanese commercial buildings are examined and DER-CAM applied to select the economically optimal DER system for each. The five building types are office, hospital, hotel, retail, and sports facility. Based on the optimization results, energy and emission reductions are evaluated. Furthermore, a Japan-U.S. comparison study of policy, technology, and utility tariffs relevant to DER installation is presented. Significant decreases in fuel consumption, carbon emissions, and energy costs were seen in the DER-CAM results. Savings were most noticeable in the sports facility (a very favourable CHP site), followed by the hospital, hotel, and office building.« less

Chromatin Constrains the Initiation and Elongation of DNA Replication.

PubMed

Devbhandari, Sujan; Jiang, Jieqing; Kumar, Charanya; Whitehouse, Iestyn; Remus, Dirk

2017-01-05

Eukaryotic chromosomal DNA is faithfully replicated in a complex series of cell-cycle-regulated events that are incompletely understood. Here we report the reconstitution of DNA replication free in solution with purified proteins from the budding yeast Saccharomyces cerevisiae. The system recapitulates regulated bidirectional origin activation; synthesis of leading and lagging strands by the three replicative DNA polymerases Pol α, Pol δ, and Pol ε; and canonical maturation of Okazaki fragments into continuous daughter strands. We uncover a dual regulatory role for chromatin during DNA replication: promoting origin dependence and determining Okazaki fragment length by restricting Pol δ progression. This system thus provides a functional platform for the detailed mechanistic analysis of eukaryotic chromosome replication. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of the kinetic parameters of the truncated catalytic subunit and holoenzyme of human DNA polymerase ε

PubMed Central

Zahurancik, Walter J.; Baranovskiy, Andrey G.; Tahirov, Tahir H.; Suo, Zucai

2015-01-01

Numerous genetic studies have provided compelling evidence to establish DNA polymerase ε (Polε) as the primary DNA polymerase responsible for leading strand synthesis during eukaryotic nuclear genome replication. Polε is a heterotetramer consisting of a large catalytic subunit that contains the conserved polymerase core domain as well as a 3′ → 5′ exonuclease domain common to many replicative polymerases. In addition, Polε possesses three small subunits that lack a known catalytic activity but associate with components involved in a variety of DNA replication and maintenance processes. Previous enzymatic characterization of the Polε heterotetramer from budding yeast suggested that the small subunits slightly enhance DNA synthesis by Polε in vitro. However, similar studies of the human Polε heterote-tramer (hPolε) have been limited by the difficulty of obtaining hPolε in quantities suitable for thorough investigation of its catalytic activity. Utilization of a baculovirus expression system for overexpression and purification of hPolε from insect host cells has allowed for isolation of greater amounts of active hPolε, thus enabling a more detailed kinetic comparison between hPolε and an active N-terminal fragment of the hPolε catalytic subunit (p261N), which is readily overexpressed in Escherichia coli. Here, we report the first pre-steady-state studies of fully-assembled hPolε. We observe that the small subunits increase DNA binding by hPolε relative to p261N, but do not increase processivity during DNA synthesis on a single-stranded M13 template. Interestingly, the 3′ → 5′ exonuclease activity of hPolε is reduced relative to p261N on matched and mismatched DNA substrates, indicating that the presence of the small subunits may regulate the proofreading activity of hPolε and sway hPolε toward DNA synthesis rather than proofreading. PMID:25684708

Energy Policy Case Study - California: Renewables and Distributed Energy Resources

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

Homer, Juliet S.; Bender, Sadie R.; Weimar, Mark R.

2016-09-19

The purpose of this document is to present a case study of energy policies in California related to power system transformation and renewable and distributed energy resources (DERs). Distributed energy resources represent a broad range of technologies that can significantly impact how much, and when, electricity is demanded from the grid. Key policies and proceedings related to power system transformation and DERs are grouped into the following categories: 1.Policies that support achieving environmental and climate goals 2.Policies that promote deployment of DERs 3.Policies that support reliability and integration of DERs 4.Policies that promote market animation and support customer choice. Majormore » challenges going forward are forecasting and modeling DERs, regulatory and utility business model issues, reliability, valuation and pricing, and data management and sharing.« less

Regulation of RNA polymerase III transcription during transformation of human IMR90 fibroblasts with defined genetic elements.

PubMed

Durrieu-Gaillard, Stéphanie; Dumay-Odelot, Hélène; Boldina, Galina; Tourasse, Nicolas J; Allard, Delphine; André, Fabrice; Macari, Françoise; Choquet, Armelle; Lagarde, Pauline; Drutel, Guillaume; Leste-Lasserre, Thierry; Petitet, Marion; Lesluyes, Tom; Lartigue-Faustin, Lydia; Dupuy, Jean-William; Chibon, Frédéric; Roeder, Robert G; Joubert, Dominique; Vagner, Stéphan; Teichmann, Martin

2018-01-01

RNA polymerase (Pol) III transcribes small untranslated RNAs that are essential for cellular homeostasis and growth. Its activity is regulated by inactivation of tumor suppressor proteins and overexpression of the oncogene c-MYC, but the concerted action of these tumor-promoting factors on Pol III transcription has not yet been assessed. In order to comprehensively analyse the regulation of Pol III transcription during tumorigenesis we employ a model system that relies on the expression of five genetic elements to achieve cellular transformation. Expression of these elements in six distinct transformation intermediate cell lines leads to the inactivation of TP53, RB1, and protein phosphatase 2A, as well as the activation of RAS and the protection of telomeres by TERT, thereby conducting to full tumoral transformation of IMR90 fibroblasts. Transformation is accompanied by moderately enhanced levels of a subset of Pol III-transcribed RNAs (7SK; MRP; H1). In addition, mRNA and/or protein levels of several Pol III subunits and transcription factors are upregulated, including increased protein levels of TFIIIB and TFIIIC subunits, of SNAPC1 and of Pol III subunits. Strikingly, the expression of POLR3G and of SNAPC1 is strongly enhanced during transformation in this cellular transformation model. Collectively, our data indicate that increased expression of several components of the Pol III transcription system accompanied by a 2-fold increase in steady state levels of a subset of Pol III RNAs is sufficient for sustaining tumor formation.

Emergence and analysis of Kuramoto-Sakaguchi-like models as an effective description for the dynamics of coupled Wien-bridge oscillators.

PubMed

English, L Q; Mertens, David; Abdoulkary, Saidou; Fritz, C B; Skowronski, K; Kevrekidis, P G

2016-12-01

We derive the Kuramoto-Sakaguchi model from the basic circuit equations governing two coupled Wien-bridge oscillators. A Wien-bridge oscillator is a particular realization of a tunable autonomous oscillator that makes use of frequency filtering (via an RC bandpass filter) and positive feedback (via an operational amplifier). In the past few years, such oscillators have started to be utilized in synchronization studies. We first show that the Wien-bridge circuit equations can be cast in the form of a coupled pair of van der Pol equations. Subsequently, by applying the method of multiple time scales, we derive the differential equations that govern the slow evolution of the oscillator phases and amplitudes. These equations are directly reminiscent of the Kuramoto-Sakaguchi-type models for the study of synchronization. We analyze the resulting system in terms of the existence and stability of various coupled oscillator solutions and explain on that basis how their synchronization emerges. The phase-amplitude equations are also compared numerically to the original circuit equations and good agreement is found. Finally, we report on experimental measurements of two coupled Wien-bridge oscillators and relate the results to the theoretical predictions.

Nonlinear dynamics of the CAM circadian rhythm in response to environmental forcing.

PubMed

Hartzell, Samantha; Bartlett, Mark S; Virgin, Lawrence; Porporato, Amilcare

2015-03-07

Crassulacean acid metabolism (CAM) photosynthesis functions as an endogenous circadian rhythm coupled to external environmental forcings of energy and water availability. This paper explores the nonlinear dynamics of a new CAM photosynthesis model (Bartlett et al., 2014) and investigates the responses of CAM plant carbon assimilation to different combinations of environmental conditions. The CAM model (Bartlett et al., 2014) consists of a Calvin cycle typical of C3 plants coupled to an oscillator of the type employed in the Van der Pol and FitzHugh-Nagumo systems. This coupled system is a function of environmental variables including leaf temperature, leaf moisture potential, and irradiance. Here, we explore the qualitative response of the system and the expected carbon assimilation under constant and periodically forced environmental conditions. The model results show how the diurnal evolution of these variables entrains the CAM cycle with prevailing environmental conditions. While constant environmental conditions generate either steady-state or periodically oscillating responses in malic acid uptake and release, forcing the CAM system with periodic daily fluctuations in light exposure and leaf temperature results in quasi-periodicity and possible chaos for certain ranges of these variables. This analysis is a first step in quantifying changes in CAM plant productivity with variables such as the mean temperature, daily temperature range, irradiance, and leaf moisture potential. Results may also be used to inform model parametrization based on the observed fluctuating regime. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chirurgie angeborener Herzfehler

NASA Astrophysics Data System (ADS)

Schreiber, Christian; Libera, Paul; Lange, Rüdiger

Störungen der embryonalen Entwicklung in der frühen Phase der Schwangerschaft können zu Fehlbildungen am Herz- und Gefäßsystem führen. Die Häufigkeit liegt bei 0.8-1 % aller lebend geborenen Kinder. In Deutschland werden jedes Jahr etwa 6.000 Kinder mit einem Herzfehler geboren (Quelle: http://www.kompetenznetzahf.de). Das Spektrum reicht von einfachen Fehlern, die das Herz-Kreislauf-System wenig beeinträchtigen, bis zu sehr schweren Herzerkrankungen, die unbehandelt zum Tode führen. Fortschritte der Kinderkardiologie, Herzchirurgie und Anästhesie ermöglichen heute ein Überleben bei über 90 % der Patienten. Auch die spezialisierte Pränataldiagnostik (vorgeburtliche Diagnostik) ermöglicht schon die frühe Weichenstellung für mögliche Therapieoptionen. Bei der chirurgischen Therapie ist jedoch festzuhalten, dass ein Herzfehler entweder korrigierend behandelt wird oder nur "palliiert“ werden kann. Bei letzterer Therapie wird bei einem Patienten eine medizinische Maßnahme durchgeführt, die nicht die Herstellung normaler Körperfunktionen zum Ziel hat, sondern in Anpassung an die physiologischen Besonderheiten des Patienten dessen Zustand lediglich stabilisiert und optimiert. Dies kann beispielsweise bei einer nicht korrigierbaren angeborenen Fehlbildung notwendig sein, bei der lediglich eine funktionelle Herzkammer vorhanden ist (z. B. hypoplastisches Linksherz). Hierbei muss eine prothetische Verbindung zur Lungenstrombahn in der Folgezeit entfernt werden.

Data-driven planning of distributed energy resources amidst socio-technical complexities

NASA Astrophysics Data System (ADS)

Jain, Rishee K.; Qin, Junjie; Rajagopal, Ram

2017-08-01

New distributed energy resources (DER) are rapidly replacing centralized power generation due to their environmental, economic and resiliency benefits. Previous analyses of DER systems have been limited in their ability to account for socio-technical complexities, such as intermittent supply, heterogeneous demand and balance-of-system cost dynamics. Here we develop ReMatch, an interdisciplinary modelling framework, spanning engineering, consumer behaviour and data science, and apply it to 10,000 consumers in California, USA. Our results show that deploying DER would yield nearly a 50% reduction in the levelized cost of electricity (LCOE) over the status quo even after accounting for socio-technical complexities. We abstract a detailed matching of consumers to DER infrastructure from our results and discuss how this matching can facilitate the development of smart and targeted renewable energy policies, programmes and incentives. Our findings point to the large-scale economic and technical feasibility of DER and underscore the pertinent role DER can play in achieving sustainable energy goals.

The potential for distributed generation in Japanese prototype buildings: A DER-CAM analysis of policy, tariff design, building energy use, and technology development (English Version)

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

Zhou, Nan; Marnay, Chris; Firestone, Ryan

The August 2003 blackout of the northeastern U.S. and CANADA caused great economic losses and inconvenience to New York City and other affected areas. The blackout was a warning to the rest of the world that the ability of conventional power systems to meet growing electricity demand is questionable. Failure of large power systems can lead to serious emergencies. Introduction of on-site generation, renewable energy such as solar and wind power and the effective utilization of exhaust heat is needed, to meet the growing energy demands of the residential and commercial sectors. Additional benefit can be achieved by integrating thesemore » distributed technologies into distributed energy resource (DER) systems. This work demonstrates a method for choosing and designing economically optimal DER systems. An additional purpose of this research is to establish a database of energy tariffs, DER technology cost and performance characteristics, and building energy consumption for Japan. This research builds on prior DER studies at the Ernest Orlando Lawrence Berkeley National Laboratory (LBNL) and with their associates in the Consortium for Electric Reliability Technology Solutions (CERTS) and operation, including the development of the microgrid concept, and the DER selection optimization program, the Distributed Energy Resources Customer Adoption Model (DER-CAM). DER-CAM is a tool designed to find the optimal combination of installed equipment and an idealized operating schedule to minimize a site's energy bills, given performance and cost data on available DER technologies, utility tariffs, and site electrical and thermal loads over a test period, usually an historic year. Since hourly electric and thermal energy data are rarely available, they are typically developed by building simulation for each of six end use loads used to model the building: electric-only loads, space heating, space cooling, refrigeration, water heating, and natural-gas-only loads. DER-CAM provides a global optimization, albeit idealized, that shows how the necessary useful energy loads can be provided for at minimum cost by selection and operation of on-site generation, heat recovery, cooling, and efficiency improvements. This study examines five prototype commercial buildings and uses DER-CAM to select the economically optimal DER system for each. The five building types are office, hospital, hotel, retail, and sports facility. Each building type was considered for both 5,000 and 10,000 square meter floor sizes. The energy consumption of these building types is based on building energy simulation and published literature. Based on the optimization results, energy conservation and the emissions reduction were also evaluated. Furthermore, a comparison study between Japan and the U.S. has been conducted covering the policy, technology and the utility tariffs effects on DER systems installations. This study begins with an examination of existing DER research. Building energy loads were then generated through simulation (DOE-2) and scaled to match available load data in the literature. Energy tariffs in Japan and the U.S. were then compared: electricity prices did not differ significantly, while commercial gas prices in Japan are much higher than in the U.S. For smaller DER systems, the installation costs in Japan are more than twice those in the U.S., but this difference becomes smaller with larger systems. In Japan, DER systems are eligible for a 1/3 rebate of installation costs, while subsidies in the U.S. vary significantly by region and application. For 10,000 m{sup 2} buildings, significant decreases in fuel consumption, carbon emissions, and energy costs were seen in the economically optimal results. This was most noticeable in the sports facility, followed the hospital and hotel. This research demonstrates that office buildings can benefit from CHP, in contrast to popular opinion. For hospitals and sports facilities, the use of waste heat is particularly effective for water and space heating. For the other building types, waste heat is most effectively used for both heating and cooling. The same examination was done for the 5,000 m{sup 2} buildings. Although CHP installation capacity is smaller and the payback periods are longer, economic, fuel efficiency, and environmental benefits are still seen. While these benefits remain even when subsidies are removed, the increased installation costs lead to lower levels of installation capacity and thus benefit.« less

Modified Van der Waals equation and law of corresponding states

NASA Astrophysics Data System (ADS)

Zhong, Wei; Xiao, Changming; Zhu, Yongkai

2017-04-01

It is well known that the Van der Waals equation is a modification of the ideal gas law, yet it can be used to describe both gas and liquid, and some important messages can be obtained from this state equation. However, the Van der Waals equation is not a precise state equation, and it does not give a good description of the law of corresponding states. In this paper, we expand the Van der Waals equation into its Taylor's series form, and then modify the fourth order expansion by changing the constant Virial coefficients into their analogous ones. Via this way, a more precise result about the law of corresponding states has been obtained, and the law of corresponding states can then be expressed as: in terms of the reduced variables, all fluids should obey the same equation with the analogous Virial coefficients. In addition, the system of 3 He with quantum effects has also been taken into consideration with our modified Van der Waals equation, and it is found that, for a normal system without quantum effect, the modification on ideal gas law from the Van der Waals equation is more significant than the real case, however, for a system with quantum effect, this modification is less significant than the real case, thus a factor is introduced in this paper to weaken or strengthen the modification of the Van der Waals equation, respectively.

Proceedings of oceans 87. The ocean - an international workplace

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

Not Available

1987-01-01

This book includes proceedings containing 347 papers. Some of the topics are: ICE -Cold ocean and ice research; ICE-1-Icebergs; ICE-2-Sea ice and structures; IE-3-Cold ocean instrumentation; ICE-4-Ocean and ice; INS-Oceanographic instrumentation; INS-1-Acoustic Doppler Current profilers; ENG-1-New solutions to old problems; ENG-2-energy from the ocean; ENG-3-Cables and connectors; POL-Policy, education and technology transfer; POL-1-International issues; POL-2-Ocean space utilization; POL-3-Economics, planning and management; SCI-6-fish stock assessment; ACI-7-Coastal currents and sediment; SCI-9-Satellite navigation; SCI-10-Deep sea minerals and methods of recovery; ODS-Fifth working symposium on oceanographic data system; ODS-1-Data base management; UND-Underwater work systems; UND-1-Diving for science.

Fission yeast RNA triphosphatase reads an Spt5 CTD code

DOE PAGES

Doamekpor, Selom K.; Schwer, Beate; Sanchez, Ana M.; ...

2014-11-20

mRNA capping enzymes are directed to nascent RNA polymerase II (Pol2) transcripts via interactions with the carboxy-terminal domains (CTDs) of Pol2 and transcription elongation factor Spt5. Fission yeast RNA triphosphatase binds to the Spt5 CTD, comprising a tandem repeat of nonapeptide motif TPAWNSGSK. Here we report the crystal structure of a Pct1·Spt5-CTD complex, which revealed two CTD docking sites on the Pct1 homodimer that engage TPAWN segments of the motif. Each Spt5 CTD interface, composed of elements from both subunits of the homodimer, is dominated by van der Waals contacts from Pct1 to the tryptophan of the CTD. The boundmore » CTD adopts a distinctive conformation in which the peptide backbone makes a tight U-turn so that the proline stacks over the tryptophan. We show that Pct1 binding to Spt5 CTD is antagonized by threonine phosphorylation. Our results fortify an emerging concept of an “Spt5 CTD code” in which (i) the Spt5 CTD is structurally plastic and can adopt different conformations that are templated by particular cellular Spt5 CTD receptor proteins; and (ii) threonine phosphorylation of the Spt5 CTD repeat inscribes a binary on–off switch that is read by diverse CTD receptors, each in its own distinctive manner.« less

Fission yeast RNA triphosphatase reads an Spt5 CTD code

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

Doamekpor, Selom K.; Schwer, Beate; Sanchez, Ana M.

mRNA capping enzymes are directed to nascent RNA polymerase II (Pol2) transcripts via interactions with the carboxy-terminal domains (CTDs) of Pol2 and transcription elongation factor Spt5. Fission yeast RNA triphosphatase binds to the Spt5 CTD, comprising a tandem repeat of nonapeptide motif TPAWNSGSK. Here we report the crystal structure of a Pct1·Spt5-CTD complex, which revealed two CTD docking sites on the Pct1 homodimer that engage TPAWN segments of the motif. Each Spt5 CTD interface, composed of elements from both subunits of the homodimer, is dominated by van der Waals contacts from Pct1 to the tryptophan of the CTD. The boundmore » CTD adopts a distinctive conformation in which the peptide backbone makes a tight U-turn so that the proline stacks over the tryptophan. We show that Pct1 binding to Spt5 CTD is antagonized by threonine phosphorylation. Our results fortify an emerging concept of an “Spt5 CTD code” in which (i) the Spt5 CTD is structurally plastic and can adopt different conformations that are templated by particular cellular Spt5 CTD receptor proteins; and (ii) threonine phosphorylation of the Spt5 CTD repeat inscribes a binary on–off switch that is read by diverse CTD receptors, each in its own distinctive manner.« less

Medizintechnik in der Tumororthopädie

NASA Astrophysics Data System (ADS)

Burgkart, Rainer; Gollwitzer, Hans; Holzapfel, Boris; Rudert, Maximilian; Rechl, Hans; Gradinger, Reiner

Die Behandlung der Knochentumoren unterlag in den letzten 20 Jahren einem raschen und stetigen Wandel, was zum einen auf die verbesserten Therapieerfolge durch den Einsatz von neoadjuvanten Therapieformen zurückzuführen ist, und andererseits von medizintechnischen Entwicklungen bezüglich moderner Schnittbilddiagnostik, neuer 3D Operationsplanungsverfahren wie das Rapid Prototyping und adaptiv modularer Tumorendoprothesensystemen u. a. begleitet wurde. Gerade die technischen Entwicklungen haben dazu geführt, daß im Bereich der Extremitäten und der Wirbelsäule radikalere Eingriffe durchgeführt werden können, was die lokale Tumorkontrolle wesentlich verbessert hat. In zunehmenden Maße werden deshalb nicht nur Kurzzeiterfolge sondern auch mittel- und langfristige Fortschritte bei der Behandlung der malignen Knochentumoren einschließlich der Metastasenbehandlung erreicht. Grundlage der Therapie ist dabei immer primär die Sicherung der Diagnose mittels Biopsie und die bildgebende sowie histologische Stadieneinteilung des malignen Tumors. Nach der Tumorresektion kann die Rekonstruktion biologisch oder mit Endoprothesensystemen erfolgen. Gerade die weiterentwickelten modularen Systeme führen zu guten funktionellen Ergebnissen mit langen Standzeiten und einer reduzierten Komplikationsrate. Individuell angefertigte Implantate sind vor allem im Bereich der Rekonstruktion komplexer Beckentumoren von großer klinischer Bedeutung.

Untersuchung der Störwirkung von LTE auf SRD Anwendungen bei 868 MHz

NASA Astrophysics Data System (ADS)

Welpot, M.; Wunderlich, S.; Gaspard, I.

2014-11-01

Moderne Hausautomatisierungssysteme, Alarmanlagen oder auch Funk-Zugangssysteme in Haus und Automobil setzen auf frei nutzbare Frequenzen in ISM/SRD-Bändern. Die rasante Zunahme an privaten und kommerziell genutzten Applikationen im SRD-Band bei 868 MHz und der Ausbau der LTE-Mobilfunknetze im Frequenzbereich unterhalb von 1 GHz ("Digital Dividend") wirft zunehmend die Frage nach der Funkverträglichkeit dieser Systeme untereinander auf. Während die SRD-Funkmodule auf eine geringe Sendeleistung von ~ +14 dBm beschränkt sind (Ralf and Thomas, 2009), beträgt die maximale LTE-Sendeleistung im Uplink nach (ETSI-Norm, 2011) +23 dBm. Zusammen mit der Einführung von LTE im Frequenzbereich unterhalb 1 GHz als DSL-Ersatz vor allem in ländlichen Gebieten, ergibt sich damit als mögliches Störszenario, dass durch die Aussendung des LTE-Endgerätes im Bereich von ca. 850 MHz die SRD-Funkverbindungen bei 868 MHz insbesondere dann gestört werden, wenn die Antennen beider Funksysteme räumlich nahe zueinander angeordnet sind und folglich nur eine geringe zusätzliche Entkopplung der Systeme bieten. In der vorliegenden Arbeit wird das LTE-Störpotential auf SRD-Empfänger praxisnah untersucht.

A comparative evaluation of polymerization stress data obtained with four different mechanical testing systems.

PubMed

Gonçalves, Flávia; Boaro, Leticia C; Ferracane, Jack L; Braga, Roberto R

2012-06-01

The null hypothesis was that mechanical testing systems used to determine polymerization stress (σ(pol)) would rank a series of composites similarly. Two series of composites were tested in the following systems: universal testing machine (UTM) using glass rods as bonding substrate, UTM/acrylic rods, "low compliance device", and single cantilever device ("Bioman"). One series had five experimental composites containing BisGMA:TEGDMA in equimolar concentrations and 60, 65, 70, 75 or 80 wt% of filler. The other series had five commercial composites: Filtek Z250 (3M ESPE), Filtek A110 (3M ESPE), Tetric Ceram (Ivoclar), Heliomolar (Ivoclar) and Point 4 (Kerr). Specimen geometry, dimensions and curing conditions were similar in all systems. σ(pol) was monitored for 10 min. Volumetric shrinkage (VS) was measured in a mercury dilatometer and elastic modulus (E) was determined by three-point bending. Shrinkage rate was used as a measure of reaction kinetics. ANOVA/Tukey test was performed for each variable, separately for each series. For the experimental composites, σ(pol) decreased with filler content in all systems, following the variation in VS. For commercial materials, σ(pol) did not vary in the UTM/acrylic system and showed very few similarities in rankings in the others tests system. Also, no clear relationships were observed between σ(pol) and VS or E. The testing systems showed a good agreement for the experimental composites, but very few similarities for the commercial composites. Therefore, comparison of polymerization stress results from different devices must be done carefully. Copyright © 2012 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Inaccurate DNA synthesis in cell extracts of yeast producing active human DNA polymerase iota.

PubMed

Makarova, Alena V; Grabow, Corinn; Gening, Leonid V; Tarantul, Vyacheslav Z; Tahirov, Tahir H; Bessho, Tadayoshi; Pavlov, Youri I

2011-01-31

Mammalian Pol ι has an unusual combination of properties: it is stimulated by Mn(2+) ions, can bypass some DNA lesions and misincorporates "G" opposite template "T" more frequently than incorporates the correct "A." We recently proposed a method of detection of Pol ι activity in animal cell extracts, based on primer extension opposite the template T with a high concentration of only two nucleotides, dGTP and dATP (incorporation of "G" versus "A" method of Gening, abbreviated as "misGvA"). We provide unambiguous proof of the "misGvA" approach concept and extend the applicability of the method for the studies of variants of Pol ι in the yeast model system with different cation cofactors. We produced human Pol ι in baker's yeast, which do not have a POLI ortholog. The "misGvA" activity is absent in cell extracts containing an empty vector, or producing catalytically dead Pol ι, or Pol ι lacking exon 2, but is robust in the strain producing wild-type Pol ι or its catalytic core, or protein with the active center L62I mutant. The signature pattern of primer extension products resulting from inaccurate DNA synthesis by extracts of cells producing either Pol ι or human Pol η is different. The DNA sequence of the template is critical for the detection of the infidelity of DNA synthesis attributed to DNA Pol ι. The primer/template and composition of the exogenous DNA precursor pool can be adapted to monitor replication fidelity in cell extracts expressing various error-prone Pols or mutator variants of accurate Pols. Finally, we demonstrate that the mutation rates in yeast strains producing human DNA Pols ι and η are not elevated over the control strain, despite highly inaccurate DNA synthesis by their extracts.

„3D-augmented-reality“-Visualisierung für die navigierte Osteosynthese von Beckenfrakturen

PubMed Central

Befrui, N.; Fischer, M.; Fuerst, B.; Lee, S.-C.; Fotouhi, J.; Weidert, S.; Johnson, A.; Euler, E.; Osgood, G.; Navab, N.; Böcker, W.

2018-01-01

Zusammenfassung Hintergrund Trotz großer Fortschritte in der Entwicklung der Hard- und Software von Navigationssystemen finden diese aufgrund ihrer vermeintlichen Komplexität, umständlichen Integration in klinische Arbeitsabläufe und fraglichen Vorteilen gegenüber konventionellen bildgebenden Verfahren bisher wenig Einsatz in den heutigen Operationssälen. Ziel der Arbeit Entwicklung einer „Augmented-reality“(AR)-Darstellung zur chirurgischen Navigation ohne Infrarot(„IR“)-Tracking-Marker und Vergleich zum konventioneller Röntgen in einem simulierten Eingriff. Material und Methoden Navigationssystem bestehend aus „Cone-beam-CT“(CBCT)-fähigem C-Bogen und „Red-green-blue-depth“(RGBD)-Kamera. Testung durch Kirschner(K)-Draht-Platzierung in Modellen unter Berücksichtigung der benötigten Zeit, der Strahlendosis und der Benutzerfreundlichkeit der Systeme. Ergebnisse Eine signifikante Reduktion der benötigten Zeit, der Röntgenbilder und der gesamten Strahlendosis bei der AR-Navigation gegenüber dem konventionellen Röntgen bei gleichbleibender Präzision. Schlussfolgerung Die AR-Navigation mithilfe der RGBD-Kamera bietet flexible und intuitive Darstellungsmöglichkeiten des Operations-situs für navigierte Osteosynthesen ohne Tracking-Marker. Hiermit ist es möglich, Operationen schneller, einfacher und mit geringerer Strahlenbelastung für Patient und OP-Personal durchzuführen. PMID:29500506

Emergence of DNA Polymerase ε Antimutators That Escape Error-Induced Extinction in Yeast

PubMed Central

Williams, Lindsey N.; Herr, Alan J.; Preston, Bradley D.

2013-01-01

DNA polymerases (Pols) ε and δ perform the bulk of yeast leading- and lagging-strand DNA synthesis. Both Pols possess intrinsic proofreading exonucleases that edit errors during polymerization. Rare errors that elude proofreading are extended into duplex DNA and excised by the mismatch repair (MMR) system. Strains that lack Pol proofreading or MMR exhibit a 10- to 100-fold increase in spontaneous mutation rate (mutator phenotype), and inactivation of both Pol δ proofreading (pol3-01) and MMR is lethal due to replication error-induced extinction (EEX). It is unclear whether a similar synthetic lethal relationship exists between defects in Pol ε proofreading (pol2-4) and MMR. Using a plasmid-shuffling strategy in haploid Saccharomyces cerevisiae, we observed synthetic lethality of pol2-4 with alleles that completely abrogate MMR (msh2Δ, mlh1Δ, msh3Δ msh6Δ, or pms1Δ mlh3Δ) but not with partial MMR loss (msh3Δ, msh6Δ, pms1Δ, or mlh3Δ), indicating that high levels of unrepaired Pol ε errors drive extinction. However, variants that escape this error-induced extinction (eex mutants) frequently emerged. Five percent of pol2-4 msh2Δ eex mutants encoded second-site changes in Pol ε that reduced the pol2-4 mutator phenotype between 3- and 23-fold. The remaining eex alleles were extragenic to pol2-4. The locations of antimutator amino-acid changes in Pol ε and their effects on mutation spectra suggest multiple mechanisms of mutator suppression. Our data indicate that unrepaired leading- and lagging-strand polymerase errors drive extinction within a few cell divisions and suggest that there are polymerase-specific pathways of mutator suppression. The prevalence of suppressors extragenic to the Pol ε gene suggests that factors in addition to proofreading and MMR influence leading-strand DNA replication fidelity. PMID:23307893

The mouse Pol I terminator is more efficient than the hepatitis delta virus ribozyme in generating influenza-virus-like RNAs with precise 3' ends in a plasmid-only-based virus rescue system.

PubMed

Feng, Liqiang; Li, Feng; Zheng, Xuehua; Pan, Weiqi; Zhou, Kai; Liu, Yichu; He, Hongxuan; Chen, Ling

2009-01-01

Reverse genetics systems for generating recombinant influenza viruses are based on two different mechanisms for obtaining the 3' end of the viral RNA: one uses the self-cleaving hepatitis delta virus ribozyme (HDVR), and the other uses the murine RNA polymerase I (Pol I) terminator. In this study, we employed EGFP and Renilla luciferase reporter constructs to compare the efficiency of both methods. Our results indicate that the murine Pol I terminator was more efficient than the HDVR, which will be helpful in choosing an influenza virus rescue system, as well as in establishing other RNA virus rescue systems.

Virtuelle Kraftwerke für Smart Markets

NASA Astrophysics Data System (ADS)

Dürr, Thomas; Heyne, Jean-Christoph

In den zurückliegenden Jahren haben insbesondere zwei Trends die Stromversorgung bestimmt: der starke Anstieg der dezentralen und der Ausbau der regenerativen Stromerzeugung, die vor allem in den Verteilnetzen stattfinden. Angesichts dieser Entwicklung gewinnen virtuelle Kraftwerke (VK) immer mehr an Bedeutung. In der frühen Phase waren VK insbesondere eine Möglichkeit, kleine dezentrale Erzeuger zu einer größeren Einheit zu bündeln und sie so marktfähig zu machen. Heute werden sie - überwacht und gesteuert über ein Dezentrales Energie-Management-System (DEMS) - gemeinsam mit Demand Response betrieben, also dem Reagieren eines Energieabnehmers auf Marktpreise. Das Demand Side Management soll zur Flexibilisierung der Industrie beitragen. Da der Ausbau der Übertragungsnetze nur schleppend vorankommt, kann die Nutzung von lastseitiger Flexibilität einen wichtigen Beitrag zur Versorgungssicherheit leisten. Im zweiten Teil des Beitrags geht es um die Entwicklung der Märkte. Großes Interesse besteht immer noch an der Regelenergie, zumal der Bedarf bis 2050 deutlich steigen wird. Die Spotmärkte Intraday und Day-Ahead wachsen kontinuierlich, deshalb werden sie für VK immer wichtiger. Am Ende gibt der Beitrag einen Ausblick auf die künftige Entwicklung, in der Regelenergie- und Spotmärkte noch eine Rolle spielen, aber andere Geschäftsmodelle wichtiger werden. Darüber hinaus geht es um langfristige Entwicklungen, die z. B. zusätzliche Serviceleistungen durch VK betreffen.

Betriebsführung multimodaler Energiesysteme

NASA Astrophysics Data System (ADS)

Mackensen, Reinhard

Die Transformation des Energiesystems von einer zentral geprägten, unidirektional orientierten und in unterschiedliche Sektoren separierten Struktur hin zu einer umfassenden, multimodalen, dezentralen und flexiblen Erzeuger- und Verbraucherlandschaft findet auf verschiedenen Ebenen statt. Randbedingung bei dieser Umwälzung ist immer die Einhaltung der Teilziele Versorgungssicherheit, Wirtschaftlichkeit und Effizienz. Im Einzelnen schlägt sich diese Transformation in einer Diversifizierung der Akteurslandschaft durch die Mechanismen des Unbundling nieder. Weiterhin finden eine Dezentralisierung der Erzeugerlandschaft und damit eine Substitution von mehrheitlich fossil betriebener Großkraftwerkstechnologie durch eine Vielzahl dezentraler Erzeuger mit zumeist regenerativem Charakter statt. Dieser Wandel hat im Wesentlichen zwei Hauptkonsequenzen. Zum einen ergeben sich durch dezentrale, flächige Verteilung der Erzeuger neue Anforderungen an den Energieaustausch, bspw. aus der Erweiterung der Stromnetze für einen bidirektionalen Energieaustausch, zum anderen werden Abstimmungsmechanismen erforderlich, welche die fluktuierende Einspeisung derart mit dem Verbrauch in Waage hält, dass sowohl elektrische Netzrestriktionen, die Qualität der Versorgung und Aspekte der Energieeffizienz und damit der Wirtschaftlichkeit berücksichtigt werden. Mögliche Antworten auf die mit dieser Betrachtung einhergehenden Fragen liegen in der Konzeption eines multimodalen Energiesystems, also in der Gesamtbetrachtung der Sektoren Strom, Wärme und Verkehr. Dieses Kapitel soll Mechanismen darlegen und Wege aufzeigen, wie eine solche Konzeption gestaltet werden kann und wie solche komplexen Systeme in der Praxis betrieben werden können.

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

Poore, WP

The vision of the Distributed Energy Research Program (DER) program of the U.S. Department of Energy (DOE) is that the United States will have the cleanest and most efficient and reliable energy system in the world by maximizing the use of affordable distributed energy resources. Electricity consumers will be able to choose from a diverse number of efficient, cost-effective, and environmentally friendly distributed energy options and easily connect them into the nation's energy infrastructure while providing benefits to their owners and other stakeholders. The long-term goal of this vision is that DER will achieve a 20% share of new electricmore » capacity additions in the United States by 2010, thereby helping to make the nation's electric power generation and delivery system more efficient, reliable, secure, clean, economical, and diverse in terms of fuel use (oil, natural gas, solar, hydroelectric, etc.) and prime mover resource (solar, wind, gas turbines, etc.). Near- and mid-term goals are to develop new technologies for implementing and operating DER and address barriers associated with DER usage and then to reduce costs and emissions and improve the efficiency and reliability of DER. Numerous strategies for meeting these goals have been developed into a research, development, and demonstration (RD&D) program that supports generation and delivery systems architecture, including modeling and simulation tools. The benefits associated with DER installations are often significant and numerous. They almost always provide tangible economic benefits, such as energy savings or transmission and distribution upgrade deferrals, as well as intangible benefits, such as power quality improvements that lengthen maintenance or repair intervals for power equipment. Also, the benefits routinely are dispersed among end users, utilities, and the public. For instance, an end user may use the DER to reduce their peak demand and save money due to lower demand charges. Reduced end user peak demand, in turn, may lower a distribution system peak load such that upgrades are deferred or avoided. This could benefit other consumers by providing them with higher reliability and power quality as well as avoiding their cost share of a distribution system upgrade. In this example, the costs of the DER may be born by the end user, but that user reaps only a share of the benefits. This report, the first product of a study to quantify the value of DER, documents initial project efforts to develop an assessment methodology. The focus of currently available site-specific DER assessment techniques are typically limited to two parties, the owner/user and the local utility. Rarely are the impacts on other stakeholders, including interconnected distribution utilities, transmission system operators, generating system operators, other local utility customers, local and regional industry and business, various levels of government, and the environment considered. The goal of this assessment is to quantify benefits and cost savings that accrue broadly across a region, recognizing that DER installations may have local, regional, or national benefits.« less

Engineering Inertial and Primary-Frequency Response for Distributed Energy Resources: Preprint

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

Dall-Anese, Emiliano; Zhao, Changhong; Guggilam, Swaroop

We propose a framework to engineer synthetic-inertia and droop-control parameters for distributed energy resources (DERs) so that the system frequency in a network composed of DERs and synchronous generators conforms to prescribed transient and steady-state performance specifications. Our approach is grounded in a second-order lumped-parameter model that captures the dynamics of synchronous generators and frequency-responsive DERs endowed with inertial and droop control. A key feature of this reduced-order model is that its parameters can be related to those of the originating higher-order dynamical model. This allows one to systematically design the DER inertial and droop-control coefficients leveraging classical frequency-domain responsemore » characteristics of second-order systems. Time-domain simulations validate the accuracy of the model-reduction method and demonstrate how DER controllers can be designed to meet steady-state-regulation and transient-performance specifications.« less

Engineering Inertial and Primary-Frequency Response for Distributed Energy Resources

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

Dall-Anese, Emiliano; Zhao, Changhong; Guggilam, Swaroop

We propose a framework to engineer synthetic-inertia and droop-control parameters for distributed energy resources (DERs) so that the system frequency in a network composed of DERs and synchronous generators conforms to prescribed transient and steady-state performance specifications. Our approach is grounded in a second-order lumped-parameter model that captures the dynamics of synchronous generators and frequency-responsive DERs endowed with inertial and droop control. A key feature of this reduced-order model is that its parameters can be related to those of the originating higherorder dynamical model. This allows one to systematically design the DER inertial and droop-control coefficients leveraging classical frequency-domain responsemore » characteristics of second-order systems. Time-domain simulations validate the accuracy of the model-reduction method and demonstrate how DER controllers can be designed to meet steady-state-regulation and transient-performance specifications.« less

North Korea’s Juche Ideology and the German Re-Unification Experience

DTIC Science & Technology

2008-06-01

repräsentativen Befragung in Ost- und Westdeutschland 2006,” Selbständige Abteilung für Medizimische Psychologie und Medizinische Soziologie der Universität...207 Ibid. “Auf anderen Ebenen – denen der Wirtschaft und der Psychologie – führte die rasche Übernahme des westdeutschen Systems zu Zerstörungen... Psychologie und Medizinische Soziologie der Universität Leipzig. (May/June 2006). http://medpsy.uniklinikum- leipzig.de/pdf/deutsche_befindlichkeiten_2006

RNA polymerase III transcription - regulated by chromatin structure and regulator of nuclear chromatin organization.

PubMed

Pascali, Chiara; Teichmann, Martin

2013-01-01

RNA polymerase III (Pol III) transcription is regulated by modifications of the chromatin. DNA methylation and post-translational modifications of histones, such as acetylation, phosphorylation and methylation have been linked to Pol III transcriptional activity. In addition to being regulated by modifications of DNA and histones, Pol III genes and its transcription factors have been implicated in the organization of nuclear chromatin in several organisms. In yeast, the ability of the Pol III transcription system to contribute to nuclear organization seems to be dependent on direct interactions of Pol III genes and/or its transcription factors TFIIIC and TFIIIB with the structural maintenance of chromatin (SMC) protein-containing complexes cohesin and condensin. In human cells, Pol III genes and transcription factors have also been shown to colocalize with cohesin and the transcription regulator and genome organizer CCCTC-binding factor (CTCF). Furthermore, chromosomal sites have been identified in yeast and humans that are bound by partial Pol III machineries (extra TFIIIC sites - ETC; chromosome organizing clamps - COC). These ETCs/COC as well as Pol III genes possess the ability to act as boundary elements that restrict spreading of heterochromatin.

Disruptive Ideas for Power Grid Security and Resilience With DER

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

Ibrahim, Erfan

This presentation by Erfan Ibrahim was prepared for NREL's 2017 Cybersecurity and Reslience Workshop on distributed energy resource (DER) best practices. The presentation provides an overview of NREL's Cyber-Physical Systems Security and Resilience R&D Center, the Center's approach to cybersecurity, and disruptive ideas for power grid security and resilience with DER.

Reisen im freien Fall - Teil 2: Das Zwillingsparadoxon aus dem Blickwinkel der ART

NASA Astrophysics Data System (ADS)

Sonne, Bernd; Weiß, Reinhard

2013-07-01

Nachdem wir uns mit den Prinzipien der ART und einigen Beispielen vertraut gemacht haben, kommen wir nun zur Berechnung des Zwillingsparadoxons aus Sicht des reisenden Zwillings. Dabei spielt das Äquivalenzprinzip eine große Rolle. Deshalb wird die Bewegungssituation noch einmal erläutert, diesmal aus Sicht von Katrin. Sie befindet sich in ihrem System S'in Ruhe. In ihrem System läuft die Zeit t'ab. Nach dem Start fühlt Katrin jedoch eine Kraft, die sie als Gravitationskraft interpretieren kann. Sie merkt es daran, dass sie in den Sitz gedrückt wird. Nach einiger Zeit werden die Triebwerke abgeschaltet, und das Raumschiff fliegt mit konstanter Geschwindigkeit weiter, Phase 2. Anschließend wird der Schub der Triebwerke solange umgekehrt, bis das Raumschiff irgendwo mit der Geschwindigkeit null am Umkehrpunkt U landet, Phase 3 (Abb. 15.1). Die Erde, auf der sich Michael befindet, bewegt sich mit x'(t') aus Sicht von Katrin im freien Fall von ihr weg, s. das Experiment mit dem steigenden Fahrstuhl in Abschn. 13.2.1.

Three-dimensional vortex-induced vibrations of supported pipes conveying fluid based on wake oscillator models

NASA Astrophysics Data System (ADS)

Wang, L.; Jiang, T. L.; Dai, H. L.; Ni, Q.

2018-05-01

The present study develops a new three-dimensional nonlinear model for investigating vortex-induced vibrations (VIV) of flexible pipes conveying internal fluid flow. The unsteady hydrodynamic forces associated with the wake dynamics are modeled by two distributed van der Pol wake oscillators. In particular, the nonlinear partial differential equations of motion of the pipe and the wake are derived, taking into account the coupling between the structure and the fluid. The nonlinear equations of motion for the coupled system are then discretized by means of the Galerkin technique, resulting in a high-dimensional reduced-order model of the system. It is shown that the natural frequencies for in-plane and out-of-plane motions of the pipe may be different at high internal flow velocities beyond the threshold of buckling instability. The orientation angle of the postbuckling configuration is time-varying due to the disturbance of hydrodynamic forces, thus yielding sometimes unexpected results. For a buckled pipe with relatively low cross-flow velocity, interestingly, examining the nonlinear dynamics of the pipe indicates that the combined effects of the cross-flow-induced resonance of the in-plane first mode and the internal-flow-induced buckling on the IL and CF oscillation amplitudes may be significant. For higher cross-flow velocities, however, the effect of internal fluid flow on the nonlinear VIV responses of the pipe is not pronounced.

Distributed Energy Resources Customer Adoption Model Plus (DER-CAM+), Version 1.0.0

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

Stadler, Michael; Cardorso, Goncalo; Mashayekh, Salman

DER-CAM+ v1.0.0 is internally referred to as DER-CAM v5.0.0. Due to fundamental changes from previous versions, a new name (DER-CAM+) will be used for DER-CAM version 5.0.0 and above. DER-CAM+ is a Decision Support Tool for Decentralized Energy Systems that has been tailored for microgrid applications, and now explicitly considers electrical and thermal networks within a microgrid, ancillary services, and operating reserve. DER-CAM was initially created as an exclusively economic energy model, able to find the cost minimizing combination and operation profile of a set of DER technologies that meet energy loads of a building or microgrid for a typicalmore » test year. The previous versions of DER-CAM were formulated without modeling the electrical/thermal networks within the microgrid, and hence, used aggregate single-node approaches. Furthermore, they were not able to consider operating reserve constraints, and microgrid revenue streams from participating in ancillary services markets. This new version DER-CAM+ considers these issues by including electrical power flow and thermal flow equations and constraints in the microgrid, revenues from various ancillary services markets, and operating reserve constraints.« less

Cybersecurity for distributed energy resources and smart inverters

DOE PAGES

Qi, Junjian; Hahn, Adam; Lu, Xiaonan; ...

2016-12-01

The increased penetration of distributed energy resources (DER) will significantly increase the number of devices that are owned and controlled by consumers and third parties. These devices have a significant dependency on digital communication and control, which presents a growing risk from cyber attacks. This paper proposes a holistic attack-resilient framework to protect the the integrated DER and the critical power grid infrastructure from malicious cyber attacks, helping ensure the secure integration of DER without harming the grid reliability and stability. Specifically, we discuss the architecture of the cyber-physical power system with a high penetration of DER and analyze themore » unique cybersecurity challenges introduced by DER integration. Next, we summarize important attack scenarios against DER, propose a systematic DER resilience analysis methodology, and develop effective and quantifiable resilience metrics and design principles. Lastly, we introduce attack prevention, detection, and response measures specifically designed for DER integration across cyber, physical device, and utility layers of the future smart grid.« less

Cybersecurity for distributed energy resources and smart inverters

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

Qi, Junjian; Hahn, Adam; Lu, Xiaonan

The increased penetration of distributed energy resources (DER) will significantly increase the number of devices that are owned and controlled by consumers and third parties. These devices have a significant dependency on digital communication and control, which presents a growing risk from cyber attacks. This paper proposes a holistic attack-resilient framework to protect the the integrated DER and the critical power grid infrastructure from malicious cyber attacks, helping ensure the secure integration of DER without harming the grid reliability and stability. Specifically, we discuss the architecture of the cyber-physical power system with a high penetration of DER and analyze themore » unique cybersecurity challenges introduced by DER integration. Next, we summarize important attack scenarios against DER, propose a systematic DER resilience analysis methodology, and develop effective and quantifiable resilience metrics and design principles. Lastly, we introduce attack prevention, detection, and response measures specifically designed for DER integration across cyber, physical device, and utility layers of the future smart grid.« less

Coordinated Optimization of Distributed Energy Resources and Smart Loads in Distribution Systems: Preprint

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

Yang, Rui; Zhang, Yingchen

2016-08-01

Distributed energy resources (DERs) and smart loads have the potential to provide flexibility to the distribution system operation. A coordinated optimization approach is proposed in this paper to actively manage DERs and smart loads in distribution systems to achieve the optimal operation status. A three-phase unbalanced Optimal Power Flow (OPF) problem is developed to determine the output from DERs and smart loads with respect to the system operator's control objective. This paper focuses on coordinating PV systems and smart loads to improve the overall voltage profile in distribution systems. Simulations have been carried out in a 12-bus distribution feeder andmore » results illustrate the superior control performance of the proposed approach.« less

Coordinated Optimization of Distributed Energy Resources and Smart Loads in Distribution Systems

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

Yang, Rui; Zhang, Yingchen

2016-11-14

Distributed energy resources (DERs) and smart loads have the potential to provide flexibility to the distribution system operation. A coordinated optimization approach is proposed in this paper to actively manage DERs and smart loads in distribution systems to achieve the optimal operation status. A three-phase unbalanced Optimal Power Flow (OPF) problem is developed to determine the output from DERs and smart loads with respect to the system operator's control objective. This paper focuses on coordinating PV systems and smart loads to improve the overall voltage profile in distribution systems. Simulations have been carried out in a 12-bus distribution feeder andmore » results illustrate the superior control performance of the proposed approach.« less

Einführung

NASA Astrophysics Data System (ADS)

Wellenreuther, Günter; Zastrow, Dieter

Reale Aufgaben der Automatisierungstechnik sind im Allgemeinen sehr komplex. Als umfassender Ausdruck für Steuerungs-, Regelungs- und Visualisierungs-Vorgänge hat sich der Begriff der Automatisierung durchgesetzt. Er beinhaltet, dass Automatisierungsgeräte selbsttätig Programme befolgen und dabei Entscheidungen auf Grund vorgegebener Führungsgrößen und rückgeführter Prozessgrößen aus der Anlage sowie erforderlicher Daten aus internen Speichern des Systems treffen, um daraus notwendige Ausgangsgrößen für den Betriebsprozess zu bilden.

[Effect of DNA polymerase beta on apoptosis and mitochondrial membrane potential induced by hydroquinone, a metabolite of benzene].

PubMed

Chen, Chen; Yang, Mo; Zhang, Zun-zhen; Wu, Mei; Deng, Wen-wen

2011-12-01

To explore the effect and mechanism of DNA polymerase β expression level on cell apoptosis and mitochondrial membrane potential induced by hydroquinone. Polβ wild-type cells (polβ+/+), polβ overexpressed cells (polβ oe) and polβ null cells (polβ-/-) were applied as a model cell system, The effect of cell apoptosis and mitochondrial membrane potential induced by different doses of hydroquinone were analyzed by flow cytometry. The ROS and ·OH assay kit were used to examine the cellular ROS and ·OH level. The activity of cellular SOD and GSH-Px were tested by Chemiluminescence method after exposed to different concentrations of hydroquinone. With the dose of hydroquinone increased, the rate of apoptosis and falling of mitochondrial membrane potential (ΔΨm) in cells were increased compared with the control. When compared with polβ+/+ cells, the rate of apoptosis in polβ-/- cells exposed to 20.00, 40.00, 80.00 µmol/L hydroquinone increased and the rate of apoptosis in polβ oe cells exposed to 10.00, 20.00, 40.00, 80.00 µmol/L hydroquinone decreased (P < 0.05). Compared with polβ+/+ cells (20.60% ± 0.57%, 37.95% ± 0.64%, 44.50% ± 1.27%, 57.55% ± 1.06%), the rate of cell which undergone mitochondrial depolarization in polβ-/- cells treated with 10.00, 20.00, 40.00, 80.00 µmol/L hydroquinone (33.60% ± 1.55%, 46.05% ± 1.77%, 52.75% ± 2.05%, 75.20% ± 0.56%) increased. The rate of cell which undergone mitochondrial depolarization in polβ oe cells exposed to 10.00, 20.00, 40.00, 80.00 µmol/L hydroquinone (16.05% ± 1.20%, 29.80% ± 1.21%, 35.15% ± 1.06%, 53.80% ± 0.85%) decreased (P < 0.05). When compared with polβ+/+ cells, fluorescent intensity of polβ-/- cells treated with different dosages of hydroquinone increased, while which of polβ oe cells decreased (P < 0.05). Compared with polβ+/+ cells, ·OH level of polβ-/- cells treated with 20.00, 40.00 µmol/L hydroquinone significantly enhanced, while which of polβ oe cells decreased sharply (P < 0.05). Under the same concentrations of hydroquinone, the activity of SOD and GSH-Px were decreased most rapidly in polβ-/- cells. The activity of SOD and GSH-Px in polβ oe cells decreased slower than in the polβ-/- cells. Hydroquinone could induced apoptosis by the generation of ROS and decrease of ΔΨm; polβ could protect cells from apoptosis induced by hydroquinone through decrease of ROS level and depolarization of mitochondria.

Obtaining Arbitrary Prescribed Mean Field Dynamics for Recurrently Coupled Networks of Type-I Spiking Neurons with Analytically Determined Weights

PubMed Central

Nicola, Wilten; Tripp, Bryan; Scott, Matthew

2016-01-01

A fundamental question in computational neuroscience is how to connect a network of spiking neurons to produce desired macroscopic or mean field dynamics. One possible approach is through the Neural Engineering Framework (NEF). The NEF approach requires quantities called decoders which are solved through an optimization problem requiring large matrix inversion. Here, we show how a decoder can be obtained analytically for type I and certain type II firing rates as a function of the heterogeneity of its associated neuron. These decoders generate approximants for functions that converge to the desired function in mean-squared error like 1/N, where N is the number of neurons in the network. We refer to these decoders as scale-invariant decoders due to their structure. These decoders generate weights for a network of neurons through the NEF formula for weights. These weights force the spiking network to have arbitrary and prescribed mean field dynamics. The weights generated with scale-invariant decoders all lie on low dimensional hypersurfaces asymptotically. We demonstrate the applicability of these scale-invariant decoders and weight surfaces by constructing networks of spiking theta neurons that replicate the dynamics of various well known dynamical systems such as the neural integrator, Van der Pol system and the Lorenz system. As these decoders are analytically determined and non-unique, the weights are also analytically determined and non-unique. We discuss the implications for measured weights of neuronal networks. PMID:26973503

Obtaining Arbitrary Prescribed Mean Field Dynamics for Recurrently Coupled Networks of Type-I Spiking Neurons with Analytically Determined Weights.

PubMed

Nicola, Wilten; Tripp, Bryan; Scott, Matthew

2016-01-01

A fundamental question in computational neuroscience is how to connect a network of spiking neurons to produce desired macroscopic or mean field dynamics. One possible approach is through the Neural Engineering Framework (NEF). The NEF approach requires quantities called decoders which are solved through an optimization problem requiring large matrix inversion. Here, we show how a decoder can be obtained analytically for type I and certain type II firing rates as a function of the heterogeneity of its associated neuron. These decoders generate approximants for functions that converge to the desired function in mean-squared error like 1/N, where N is the number of neurons in the network. We refer to these decoders as scale-invariant decoders due to their structure. These decoders generate weights for a network of neurons through the NEF formula for weights. These weights force the spiking network to have arbitrary and prescribed mean field dynamics. The weights generated with scale-invariant decoders all lie on low dimensional hypersurfaces asymptotically. We demonstrate the applicability of these scale-invariant decoders and weight surfaces by constructing networks of spiking theta neurons that replicate the dynamics of various well known dynamical systems such as the neural integrator, Van der Pol system and the Lorenz system. As these decoders are analytically determined and non-unique, the weights are also analytically determined and non-unique. We discuss the implications for measured weights of neuronal networks.

Deficient brain RNA polymerase and altered nucleolar structure persists until day 8 after perinatal asphyxia of the rat.

PubMed

Kastner, Philomena; Mosgoeller, Wilhelm; Fang-Kircher, Susanne; Kitzmueller, Erwin; Kirchner, Liselotte; Hoeger, Harald; Seither, Peter; Lubec, Gert; Lubec, Barbara

2003-01-01

RNA polymerases (POL) are integral constituents of the protein synthesis machinery, with POL I and POL III coding for ribosomal RNA and POL II coding for protein. POL I is located in the nucleolus and transcribes class I genes, those that code for large ribosomal RNA. It has been reported that the POL system is seriously affected in perinatal asphyxia (PA) immediately after birth. Because POL I is necessary for protein synthesis and brain protein synthesis was shown to be deranged after hypoxic-ischemic conditions, we aimed to study whether POL derangement persists in a simple, well-documented animal model of graded global PA at the activity, mRNA, protein, and morphologic level until 8 d after the asphyctic insult. Nuclear POL I activity was determined according to a radiochemical method; mRNA steady state and protein levels of RPA4O-an essential subunit of POL I and III-were evaluated by blotting methods; and the POL I subunit polymerase activating factor-53 was evaluated using immunohistochemistry. Silver staining and transmission electron microscopy were used to examine the nucleolus. At the eighth day after PA, nuclear POL I decreased with the length of the asphyctic period, whereas mRNA and protein levels for RPA4O were unchanged. The subunit polymerase activating factor-53, however, was unambiguously reduced in several brain regions. Dramatic changes of nucleolar morphology were observed, the main finding being nucleolar disintegration at the electron microscopy level. We suggest that severe acidosis and/or deficient protein kinase C in the brain during the asphyctic period may be responsible for disintegration of the nucleolus as well as for decreased POL activity persisting until the eighth day after PA. The biologic effect may be that PA causes impaired RNA and protein synthesis, which has been already observed in hypoxic-ischemic states.

Inaccurate DNA Synthesis in Cell Extracts of Yeast Producing Active Human DNA Polymerase Iota

PubMed Central

Makarova, Alena V.; Grabow, Corinn; Gening, Leonid V.; Tarantul, Vyacheslav Z.; Tahirov, Tahir H.; Bessho, Tadayoshi; Pavlov, Youri I.

2011-01-01

Mammalian Pol ι has an unusual combination of properties: it is stimulated by Mn2+ ions, can bypass some DNA lesions and misincorporates “G” opposite template “T” more frequently than incorporates the correct “A.” We recently proposed a method of detection of Pol ι activity in animal cell extracts, based on primer extension opposite the template T with a high concentration of only two nucleotides, dGTP and dATP (incorporation of “G” versus “A” method of Gening, abbreviated as “misGvA”). We provide unambiguous proof of the “misGvA” approach concept and extend the applicability of the method for the studies of variants of Pol ι in the yeast model system with different cation cofactors. We produced human Pol ι in baker's yeast, which do not have a POLI ortholog. The “misGvA” activity is absent in cell extracts containing an empty vector, or producing catalytically dead Pol ι, or Pol ι lacking exon 2, but is robust in the strain producing wild-type Pol ι or its catalytic core, or protein with the active center L62I mutant. The signature pattern of primer extension products resulting from inaccurate DNA synthesis by extracts of cells producing either Pol ι or human Pol η is different. The DNA sequence of the template is critical for the detection of the infidelity of DNA synthesis attributed to DNA Pol ι. The primer/template and composition of the exogenous DNA precursor pool can be adapted to monitor replication fidelity in cell extracts expressing various error-prone Pols or mutator variants of accurate Pols. Finally, we demonstrate that the mutation rates in yeast strains producing human DNA Pols ι and η are not elevated over the control strain, despite highly inaccurate DNA synthesis by their extracts. PMID:21304950

Unfolding an electronic integrate-and-fire circuit.

PubMed

Carrillo, Humberto; Hoppensteadt, Frank

2010-01-01

Many physical and biological phenomena involve accumulation and discharge processes that can occur on significantly different time scales. Models of these processes have contributed to understand excitability self-sustained oscillations and synchronization in arrays of oscillators. Integrate-and-fire (I+F) models are popular minimal fill-and-flush mathematical models. They are used in neuroscience to study spiking and phase locking in single neuron membranes, large scale neural networks, and in a variety of applications in physics and electrical engineering. We show here how the classical first-order I+F model fits into the theory of nonlinear oscillators of van der Pol type by demonstrating that a particular second-order oscillator having small parameters converges in a singular perturbation limit to the I+F model. In this sense, our study provides a novel unfolding of such models and it identifies a constructible electronic circuit that is closely related to I+F.

Modelling vertical human walking forces using self-sustained oscillator

NASA Astrophysics Data System (ADS)

Kumar, Prakash; Kumar, Anil; Racic, Vitomir; Erlicher, Silvano

2018-01-01

This paper proposes a model of a self-sustained oscillator which can generate reliably the vertical contact force between the feet of a healthy pedestrian and the supporting flat rigid surface. The model is motivated by the self-sustained nature of the walking process, i.e. a pedestrian generates the required inner energy to sustain its repetitive body motion. The derived model is a fusion of the well-known Rayleigh, Van der Pol and Duffing oscillators. Some additional nonlinear terms are added to produce both the odd and even harmonics observed in the experimentally measured force data. The model parameters were derived from force records due to twelve pedestrians walking on an instrumented treadmill at ten speeds using a linear least square technique. The stability analysis was performed using the energy balance method and perturbation method. The results obtained from the model show a good agreement with the experimental results.

Transition from homogeneous to inhomogeneous limit cycles: Effect of local filtering in coupled oscillators

NASA Astrophysics Data System (ADS)

Banerjee, Tanmoy; Biswas, Debabrata; Ghosh, Debarati; Bandyopadhyay, Biswabibek; Kurths, Jürgen

2018-04-01

We report an interesting symmetry-breaking transition in coupled identical oscillators, namely, the continuous transition from homogeneous to inhomogeneous limit cycle oscillations. The observed transition is the oscillatory analog of the Turing-type symmetry-breaking transition from amplitude death (i.e., stable homogeneous steady state) to oscillation death (i.e., stable inhomogeneous steady state). This novel transition occurs in the parametric zone of occurrence of rhythmogenesis and oscillation death as a consequence of the presence of local filtering in the coupling path. We consider paradigmatic oscillators, such as Stuart-Landau and van der Pol oscillators, under mean-field coupling with low-pass or all-pass filtered self-feedback and through a rigorous bifurcation analysis we explore the genesis of this transition. Further, we experimentally demonstrate the observed transition, which establishes its robustness in the presence of parameter fluctuations and noise.

Kinetic Competition between Elongation Rate and Binding of NELF Controls Promoter Proximal Pausing

PubMed Central

Li, Jian; Liu, Yingyun; Rhee, Ho Sung; Ghosh, Saikat Kumar B.; Bai, Lu; Pugh, B. Franklin; Gilmour, David S.

2013-01-01

Summary Pausing of RNA polymerase II (Pol II) 20-60 bp downstream of transcription start sites is a major checkpoint during transcription in animal cells. Mechanisms that control pausing are largely unknown. We developed permanganate-ChIP-seq to evaluate the state of Pol II at promoters throughout the Drosophila genome, and a biochemical system that reconstitutes promoter-proximal pausing to define pausing mechanisms. Stable open complexes of Pol II are largely absent from the transcription start sites of most mRNA genes, but are present at snRNA genes and the highly transcribed heat shock genes following their induction. The location of the pause is influenced by the timing between when NELF loads onto Pol II and how fast Pol II escapes the promoter region. Our biochemical analysis reveals that the sequence-specific transcription factor, GAF, orchestrates efficient pausing by recruiting NELF to promoters before transcription initiation and by assisting in loading NELF onto Pol II after initiation. PMID:23746353

Understanding the Physical and Molecular Basis of Stability of Arabidopsis DNA Pol λ under UV-B and High NaCl Stress.

PubMed

Roy, Sujit; Banerjee, Victor; Das, Kali Pada

2015-01-01

Here, we have investigated the physical and molecular basis of stability of Arabidopsis DNA Pol λ, the sole X family DNA polymerase member in plant genome, under UV-B and salinity stress in connection with the function of the N-terminal BRCT (breast cancer-associated C terminus) domain and Ser-Pro rich region in the regulation of the overall structure of this protein. Tryptophan fluorescence studies, fluorescence quenching and Bis-ANS binding experiments using purified recombinant full length Pol λ and its N-terminal deletion forms have revealed UV-B induced conformational change in BRCT domain deficient Pol λ. On the other hand, the highly conserved C-terminal catalytic core PolX domain maintained its tertiary folds under similar condition. Circular dichroism (CD) and fourier transform infrared (FT-IR) spectral studies have indicated appreciable change in the secondary structural elements in UV-B exposed BRCT domain deficient Pol λ. Increased thermodynamic stability of the C-terminal catalytic core domain suggested destabilizing effect of the N-terminal Ser-Pro rich region on the protein structure. Urea-induced equilibrium unfolding studies have revealed increased stability of Pol λ and its N-terminal deletion mutants at high NaCl concentration. In vivo aggregation studies using transient expression systems in Arabidopsis and tobacco indicated possible aggregation of Pol λ lacking the BRCT domain. Immunoprecipitation assays revealed interaction of Pol λ with the eukaryotic molecular chaperone HSP90, suggesting the possibility of regulation of Pol λ stability by HSP90 in plant cell. Overall, our results have provided one of the first comprehensive information on the biophysical characteristics of Pol λ and indicated the importance of both BRCT and Ser-Pro rich modules in regulating the stability of this protein under genotoxic stress in plants.

Replicative DNA Polymerase δ but Not ε Proofreads Errors in Cis and in Trans

PubMed Central

Flood, Carrie L.; Rodriguez, Gina P.; Bao, Gaobin; Shockley, Arthur H.; Kow, Yoke Wah; Crouse, Gray F.

2015-01-01

It is now well established that in yeast, and likely most eukaryotic organisms, initial DNA replication of the leading strand is by DNA polymerase ε and of the lagging strand by DNA polymerase δ. However, the role of Pol δ in replication of the leading strand is uncertain. In this work, we use a reporter system in Saccharomyces cerevisiae to measure mutation rates at specific base pairs in order to determine the effect of heterozygous or homozygous proofreading-defective mutants of either Pol ε or Pol δ in diploid strains. We find that wild-type Pol ε molecules cannot proofread errors created by proofreading-defective Pol ε molecules, whereas Pol δ can not only proofread errors created by proofreading-defective Pol δ molecules, but can also proofread errors created by Pol ε-defective molecules. These results suggest that any interruption in DNA synthesis on the leading strand is likely to result in completion by Pol δ and also explain the higher mutation rates observed in Pol δ-proofreading mutants compared to Pol ε-proofreading defective mutants. For strains reverting via AT→GC, TA→GC, CG→AT, and GC→AT mutations, we find in addition a strong effect of gene orientation on mutation rate in proofreading-defective strains and demonstrate that much of this orientation dependence is due to differential efficiencies of mispair elongation. We also find that a 3′-terminal 8 oxoG, unlike a 3′-terminal G, is efficiently extended opposite an A and is not subject to proofreading. Proofreading mutations have been shown to result in tumor formation in both mice and humans; the results presented here can help explain the properties exhibited by those proofreading mutants. PMID:25742645

Primary Frequency Response with Aggregated DERs: Preprint

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

Guggilam, Swaroop S.; Dhople, Sairaj V.; Zhao, Changhong

2017-03-03

Power networks have to withstand a variety of disturbances that affect system frequency, and the problem is compounded with the increasing integration of intermittent renewable generation. Following a large-signal generation or load disturbance, system frequency is arrested leveraging primary frequency control provided by governor action in synchronous generators. In this work, we propose a framework for distributed energy resources (DERs) deployed in distribution networks to provide (supplemental) primary frequency response. Particularly, we demonstrate how power-frequency droop slopes for individual DERs can be designed so that the distribution feeder presents a guaranteed frequency-regulation characteristic at the feeder head. Furthermore, the droopmore » slopes are engineered such that injections of individual DERs conform to a well-defined fairness objective that does not penalize them for their location on the distribution feeder. Time-domain simulations for an illustrative network composed of a combined transmission network and distribution network with frequency-responsive DERs are provided to validate the approach.« less

An Optimization and Assessment on DG adoption in JapanesePrototype Buildings

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

Zhou, Nan; Marnay, Chris; Firestone, Ryan

2005-11-30

This research investigates a method of choosing economicallyoptimal DER, expanding on prior studies at the Berkeley Lab using the DERdesign optimization program, the Distributed Energy Resources CustomerAdoption Model (DER-CAM). DER-CAM finds the optimal combination ofinstalled equipment from available DER technologies, given prevailingutility tariffs, site electrical and thermal loads, and a menu ofavailable equipment. It provides a global optimization, albeit idealized,that shows how the site energy load scan be served at minimum cost byselection and operation of on-site generation, heat recovery, andcooling. Five prototype Japanese commercial buildings are examined andDER-CAM applied to select thee conomically optimal DER system for each.The fivemore » building types are office, hospital, hotel, retail, and sportsfacility. Based on the optimization results, energy and emissionreductions are evaluated. Furthermore, a Japan-U.S. comparison study ofpolicy, technology, and utility tariffs relevant to DER installation ispresented. Significant decreases in fuel consumption, carbon emissions,and energy costs were seen in the DER-CAM results. Savings were mostnoticeable in the sports facility, followed by the hospital, hotel, andoffice building.« less

Die Digitalisierung der Energiewirtschaft: Potenziale und Herausforderungen der IKT-Branche für Utility 4.0

NASA Astrophysics Data System (ADS)

Aichele, Christian; Schönberger, Marius

Energieunternehmen haben auf dem Weg zur digitalen Transformation noch viele Herausforderungen zu bewältigen. Ein besonderer Schwerpunkt liegt derzeit auf der Modernisierung der IT-Systeme. Ausgangspunkt hierzu ist, dass sich bei den Endkonsumenten Mobile Applikationen, Smartphones, Tablet-PCs oder Smart TVs einer immensen Beliebtheit erfreuen. Durch diese Technologien wird die physische und virtuelle Welt in immer weiter zunehmendem Maße miteinander verknüpft. Mobile Applikation können einen wahren Hype hervorrufen und Verhaltensweisen auch nachhaltig verändern (ein Beispiel hierfür ist Pokémon Go, eine App die ein virtuelles Spiel mit der realen Umgebung kombiniert und die erstmalig auch eingefleischte Zocker aus der Anonymität ihrer häuslichen Umgebung hervorlocken konnte und für analoge Bewegung im Freien sorgte).

Ionospheric Specifications for SAR Interferometry (ISSI)

NASA Technical Reports Server (NTRS)

Pi, Xiaoqing; Chapman, Bruce D; Freeman, Anthony; Szeliga, Walter; Buckley, Sean M.; Rosen, Paul A.; Lavalle, Marco

2013-01-01

The ISSI software package is designed to image the ionosphere from space by calibrating and processing polarimetric synthetic aperture radar (PolSAR) data collected from low Earth orbit satellites. Signals transmitted and received by a PolSAR are subject to the Faraday rotation effect as they traverse the magnetized ionosphere. The ISSI algorithms combine the horizontally and vertically polarized (with respect to the radar system) SAR signals to estimate Faraday rotation and ionospheric total electron content (TEC) with spatial resolutions of sub-kilometers to kilometers, and to derive radar system calibration parameters. The ISSI software package has been designed and developed to integrate the algorithms, process PolSAR data, and image as well as visualize the ionospheric measurements. A number of tests have been conducted using ISSI with PolSAR data collected from various latitude regions using the phase array-type L-band synthetic aperture radar (PALSAR) onboard Japan Aerospace Exploration Agency's Advanced Land Observing Satellite mission, and also with Global Positioning System data. These tests have demonstrated and validated SAR-derived ionospheric images and data correction algorithms.

Mixtures of Bosonic and Fermionic atoms

NASA Astrophysics Data System (ADS)

Albus, Alexander

2003-12-01

The theory of atomic Boson-Fermion mixtures in the dilute limit beyond mean-field is considered in this thesis. Extending the formalism of quantum field theory we derived expressions for the quasi-particle excitation spectra, the ground state energy, and related quantities for a homogenous system to first order in the dilute gas parameter. In the framework of density functional theory we could carry over the previous results to inhomogeneous systems. We then determined to density distributions for various parameter values and identified three different phase regions: (i) a stable mixed regime, (ii) a phase separated regime, and (iii) a collapsed regime. We found a significant contribution of exchange-correlation effects in the latter case. Next, we determined the shift of the Bose-Einstein condensation temperature caused by Boson-Fermion interactions in a harmonic trap due to redistribution of the density profiles. We then considered Boson-Fermion mixtures in optical lattices. We calculated the criterion for stability against phase separation, identified the Mott-insulating and superfluid regimes both, analytically within a mean-field calculation, and numerically by virtue of a Gutzwiller Ansatz. We also found new frustrated ground states in the limit of very strong lattices. ----Anmerkung: Der Autor ist Träger des durch die Physikalische Gesellschaft zu Berlin vergebenen Carl-Ramsauer-Preises 2004 für die jeweils beste Dissertation der vier Universitäten Freie Universität Berlin, Humboldt-Universität zu Berlin, Technische Universität Berlin und Universität Potsdam. Ziel der Arbeit war die systematische theoretische Behandlung von Gemischen aus bosonischen und fermionischen Atomen in einem Parameterbereich, der sich zur Beschreibung von aktuellen Experimenten mit ultra-kalten atomaren Gasen eignet. Zuerst wurde der Formalismus der Quantenfeldtheorie auf homogene, atomare Boson-Fermion Gemische erweitert, um grundlegende Größen wie Quasiteilchenspektren, die Grundzustandsenergie und daraus abgeleitete Größen über die Molekularfeldtheorie hinaus zu berechnen. Unter Zuhilfenahme der dieser Resultate System wurde ein Boson-Fermion Gemisch in einem Fallenpotential im Rahmen der Dichtefunktionaltheorie beschrieben. Daraus konnten die Dichteprofile ermittelt werden und es ließen sich drei Bereiche im Phasendiagramm identifizieren: (i) ein Bereich eines stabilen Gemisches, (ii) ein Bereich, in dem die Spezies entmischt sind und (iii) ein Bereich, in dem das System kollabiert. Im letzten dieser drei Fällen waren Austausch--Korrelationseffekte signifikant. Weiterhin wurde die Änderung der kritischen Temperatur der Bose-Einstein-Kondensation aufgrund der Boson-Fermion-Wechselwirkung berechnet. Verursacht wird dieser Effekt von Dichtumverteilungen aufgrund der Wechselwirkung. Dann wurden Boson-Fermion Gemische in optischen Gittern betrachtet. Ein Stabilitätskriterium gegen Phasenentmischung wurde gefunden und es ließen sich Bedingungen für einen supraflüssig zu Mott-isolations Phasenübergang angeben. Diese wurden sowohl mittels einer Molekularfeldrechnung als auch numerisch im Rahmen eines Gutzwilleransatzes gefunden. Es wurden weiterhin neuartige frustrierte Grundzustände im Fall von sehr großen Gitterstärken gefunden.

Cellular response of healing tissue to DegraPol tube implantation in rabbit Achilles tendon rupture repair: an in vivo histomorphometric study.

PubMed

Buschmann, Johanna; Meier-Bürgisser, Gabriella; Bonavoglia, Eliana; Neuenschwander, Peter; Milleret, Vincent; Giovanoli, Pietro; Calcagni, Maurizio

2013-05-01

In tendon rupture repair, improvements such as higher primary repair strength, anti-adhesion and accelerated healing are needed. We developed a potential carrier system of an electrospun DegraPol tube, which was tightly implanted around a transected and conventionally sutured rabbit Achilles tendon. Histomorphometric analysis of the tendon tissue 12 weeks postoperation showed that the tenocyte density, tenocyte morphology and number of inflammation zones were statistically equivalent, whether or not DegraPol tube was implanted; only the collagen fibres were slightly less parallelly orientated in the tube-treated case. Comparison of rabbits that were operated on both hind legs with ones that were operated on only one hind leg showed that there were significantly more inflammation zones in the two-leg cases compared to the one-leg cases, while the implantation of a DegraPol tube had no such adverse effects. These findings are a prerequisite for using DegraPol tube as a carrier system for growth factors, cytokines or stem cells in order to accelerate the healing process of tendon tissue. Copyright © 2012 John Wiley & Sons, Ltd.

The Lyapunov-Krasovskii theorem and a sufficient criterion for local stability of isochronal synchronization in networks of delay-coupled oscillators

NASA Astrophysics Data System (ADS)

Grzybowski, J. M. V.; Macau, E. E. N.; Yoneyama, T.

2017-05-01

This paper presents a self-contained framework for the stability assessment of isochronal synchronization in networks of chaotic and limit-cycle oscillators. The results were based on the Lyapunov-Krasovskii theorem and they establish a sufficient condition for local synchronization stability of as a function of the system and network parameters. With this in mind, a network of mutually delay-coupled oscillators subject to direct self-coupling is considered and then the resulting error equations are block-diagonalized for the purpose of studying their stability. These error equations are evaluated by means of analytical stability results derived from the Lyapunov-Krasovskii theorem. The proposed approach is shown to be a feasible option for the investigation of local stability of isochronal synchronization for a variety of oscillators coupled through linear functions of the state variables under a given undirected graph structure. This ultimately permits the systematic identification of stability regions within the high-dimensionality of the network parameter space. Examples of applications of the results to a number of networks of delay-coupled chaotic and limit-cycle oscillators are provided, such as Lorenz, Rössler, Cubic Chua's circuit, Van der Pol oscillator and the Hindmarsh-Rose neuron.

Pepino mosaic virus RNA-Dependent RNA Polymerase POL Domain Is a Hypersensitive Response-Like Elicitor Shared by Necrotic and Mild Isolates.

PubMed

Sempere, Raquel N; Gómez-Aix, Cristina; Ruíz-Ramón, Fabiola; Gómez, Pedro; Hasiów-Jaroszewska, Beata; Sánchez-Pina, María Amelia; Aranda, Miguel A

2016-04-01

Pepino mosaic virus (PepMV) is an emerging pathogen that represents a serious threat to tomato production worldwide. PepMV-induced diseases manifest with a wide range of symptoms, including systemic necrosis. Our results showed that PepMV accumulation depends on the virus isolate, tomato cultivar, and environmental conditions, and associates with the development of necrosis. Substitution of lysine for glutamic acid at position 67 in the triple gene block 3 (TGB3) protein, previously described as a necrosis determinant, led to increased virus accumulation and was necessary but not sufficient to induce systemic necrosis. Systemic necrosis both in tomato and Nicotiana benthamiana shared hypersensitive response (HR) features, allowing the assessment of the role of different genomic regions on necrosis induction. Overexpression of both TGB3 and the polymerase domain (POL) of the RNA-dependent RNA polymerase (RdRp) resulted in necrosis, although only local expression of POL triggered HR-like symptoms. Our results also indicated that the necrosis-eliciting activity of POL resides in its highly conserved "palm" domain, and that necrosis was jasmonic acid-dependent but not salicylic acid-dependent. Altogether, our data suggest that the RdRp-POL domain plays an important role in PepMV necrosis induction, with necrosis development depending on the virus accumulation level, which can be modulated by the nature of TGB3, host genotype and environmental conditions.

Sentinel-Lymphknoten-Biopsie des Melanoms mittels Indocyaningrün und "FOVIS"-System.

PubMed

Göppner, Daniela; Nekwasil, Stephan; Jellestad, Anne; Sachse, Alexander; Schönborn, Karl-Heinz; Gollnick, Harald

2017-02-01

Der Nachweis metastatischer Infiltrate im Sentinel-Lymphkoten (SLN) gilt als wesentlicher prognostischer Faktor des Melanoms. Alternativ zur Farbstoffmethode mit Patentblau zum Goldstandard der SLN-Biopsie (SLNB) mittels Radiokolloid wird die fluoreszenzoptische Darstellung mit Hilfe von Indocyaningrün (ICG) und Nahinfrarot (NIR)-Kamerasystem kommuniziert. Im Vergleich zur konventionellen Methode wurde die Wertigkeit des ICG-/NIR-Verfahrens in Abhängigkeit vom Body-Mass-Index (BMI) des Patienten und der Konzentration von ICG bezüglich der Visualisierung des Lymphabstroms und des SLNs untersucht. An zehn Patienten wurde die SLNB mittels Technetium-99m, Patentblau und ICG durchgeführt. Die Fluoreszenz-Darstellung von Lymphbahnen und SLN erfolgte in Echtzeit mittels der NIR-Kameratechnik "FOVIS". Je nach erzielter Bildqualität wurde ICG in einer Dosis von 0,25 mg bis 2,5 mg intrakutan appliziert. Neun der zehn SLN wurden fluoreszenzoptisch identifiziert (90 %), alle zehn radioaktiv (100 %), nur acht (80 %) mittels ICG-Grünfärbung bzw. Patenblau-Markierung. Transdermal wurde ein SLN dargestellt (10 %). In Korrelation zum BMI waren höhere ICG-Mengen, bis zu 2,5 mg intrakutan absolut, in der Darstellung der Lymphbahnen von Vorteil. Die SLN-Fluoreszenzmarkierung mit dem ICG/NIR-Kamera-System "FOVIS" stellt eine sichere Alternative zur Farbstoffmethode mit Patentblau ergänzend zur Radiokolloidmethode mit Technetium-99m dar. Weitere Studien zur optimalen Dosierung von ICG und transdermalen Bildgebung in Relation zum BMI sind notwendig. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

A Quality Assessment Method Based on Common Distributed Targets for GF-3 Polarimetric SAR Data.

PubMed

Jiang, Sha; Qiu, Xiaolan; Han, Bing; Hu, Wenlong

2018-03-07

The GaoFen-3 (GF-3) satellite, launched on 10 August 2016, is the first C-band polarimetric synthetic aperture radar (PolSAR) satellite in China. The PolSAR system of GF-3 can collect a significant wealth of information for geophysical research and applications. Being used for related applications, GF-3 PolSAR images must be of good quality. It is necessary to evaluate the quality of polarimetric data and achieve the normalized quality monitoring during 8-year designed life of GF-3. In this study, a new quality assessment method of PolSAR data based on common distributed targets is proposed, and the performance of the method is analyzed by simulations and GF-3 experiments. We evaluate the quality of GF-3 PolSAR data by this method. Results suggest that GF-3 antenna is highly isolated, and the quality of calibrated data satisfies the requests of quantitative applications.

Optimizing DER Participation in Inertial and Primary-Frequency Response

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

Dall-Anese, Emiliano; Zhao, Changhong; Guggilam, Swaroop

This paper develops an approach to enable the optimal participation of distributed energy resources (DERs) in inertial and primary-frequency response alongside conventional synchronous generators. Leveraging a reduced-order model description of frequency dynamics, DERs' synthetic inertias and droop coefficients are designed to meet time-domain performance objectives of frequency overshoot and steady-state regulation. Furthermore, an optimization-based method centered around classical economic dispatch is developed to ensure that DERs share the power injections for inertial- and primary-frequency response in proportion to their power ratings. Simulations for a modified New England test-case system composed of ten synchronous generators and six instances of the IEEEmore » 37-node test feeder with frequency-responsive DERs validate the design strategy.« less

“Gate-keeper” Residues and Active-Site Rearrangements in DNA Polymerase μ Help Discriminate Non-cognate Nucleotides

PubMed Central

Li, Yunlang; Schlick, Tamar

2013-01-01

Incorporating the cognate instead of non-cognate substrates is crucial for DNA polymerase function. Here we analyze molecular dynamics simulations of DNA polymerase μ (pol μ) bound to different non-cognate incoming nucleotides including A:dCTP, A:dGTP, A(syn):dGTP, A:dATP, A(syn):dATP, T:dCTP, and T:dGTP to study the structure-function relationships involved with aberrant base pairs in the conformational pathway; while a pol μ complex with the A:dTTP base pair is available, no solved non-cognate structures are available. We observe distinct differences of the non-cognate systems compared to the cognate system. Specifically, the motions of active-site residue His329 and Asp330 distort the active site, and Trp436, Gln440, Glu443 and Arg444 tend to tighten the nucleotide-binding pocket when non-cognate nucleotides are bound; the latter effect may further lead to an altered electrostatic potential within the active site. That most of these “gate-keeper” residues are located farther apart from the upstream primer in pol μ, compared to other X family members, also suggests an interesting relation to pol μ's ability to incorporate nucleotides when the upstream primer is not paired. By examining the correlated motions within pol μ complexes, we also observe different patterns of correlations between non-cognate systems and the cognate system, especially decreased interactions between the incoming nucleotides and the nucleotide-binding pocket. Altered correlated motions in non-cognate systems agree with our recently proposed hybrid conformational selection/induced-fit models. Taken together, our studies propose the following order for difficulty of non-cognate system insertions by pol μ: T:dGTP

[Exploration of relationship between the expression level of DNA polymerase beta and 60Co gamma-ray radiosensitivity].

PubMed

Cui, Jie; Xu, Xin; Yang, Mo; Chen, Chen; Zhao, Wei; Wu, Mei; Zhang, Zun-zhen

2011-11-01

To explore the relationship between the expression level of DNA polymerase beta (pol beta) and 60Co gamma-ray radiosensitivity and provide a basis on improving the efficiency of radiotherapy theoretically. pol beta wild-type cells (pol beta +/+), pol beta null cells (pol beta -/-) and pol beta overexpressed cells (polp beta oe) were applied as a model system. The radiosensitivity of 60Co gamma-ray on the cell was detected by MTT assay and clone formation assay. The DCFH-DA fluorescent probe was used to examine the cellular ROS after 60Co gamma-rays radiation. MTT assay showed that after radiation by 60Co gamma-rays followed with 72 h incubation, the cell viabilities in the three kinds of cells decreased significantly with a dose-response relationship (r-/+ = -0.976, r-/- = -0.977, r(oe) = -0.982, P<0.05). In addition, the viability of pol beta -/- cell was lower than those of other two kinds of cells at the same dose (P<0.05). Likewise, the colony number and colony formation rate in all tested cells also decreased after exposure to 60Co gamma-rays. The ROS level in the three kinds of cells was enhanced after treatment with 60Co gamma-ray, and the ROS level in pol beta -/- cells was much higher than that in the other two kinds of cells (P<0.05). Cell death caused by 60Co gamma-ray may associated with the DNA oxidative damage mediated by ROS; Overexpression of pol beta could protect against oxidative DNA damage, thus the cell apoptosis/death, thereby leading to reducing the radiosensitivity of 60Co gamma-rays, while null of DNA pol beta could increase radiosensitivity of 60Co gamma-rays by compromising the DNA repair.

Konsistente Verknüpfung von Aktivitäts-, Sequenz- und Zustandsdiagrammen

NASA Astrophysics Data System (ADS)

Ebrecht, Lars; Lemmer, Karsten

Der folgende Beitrag stellt eine formale, generische Verhaltensstruktur und Semantik vor, die die Basis für die konsistente Verknüpfung der drei wichtigsten UML Verhaltensdiagramme bildet. Es wird gezeigt, wie sich das grobe und übersichtliche Verhalten in Aktivitätsdiagrammen, das detaillierte Schnittstellenverhalten in Sequenzdiagrammen und detaillierte Verhaltensmodelle in Zustandsdiagrammen mit Hilfe der Semantik konsistent miteinander verknüpfen lassen und die Inhalte der drei genannten Verhaltensdiagramme eindeutig miteinander in Beziehung gebracht werden können. Als Anwendungsbeispiel wird die komplexe, sicherheits- und echtzeitkritische zugseitige Komponente des Europäischen Leit- und Sicherungstechnik Systems (ETCS) verwendet.

Grundlagen und Grundbegriffe der Messtechnik

NASA Astrophysics Data System (ADS)

Plaßmann, Wilfried

Es ist eine wesentliche Aufgabe der Messtechnik, technische Vorgänge quantitativ zu erfassen und anhand der gemessenen Größen Funktionsabläufe zu steuern. Als Beispiel sei ein Kraftwerk zur Energieerzeugung genannt, bei dem nur über die Messung von Temperaturen, Leistungen, Drücken und anderen Größen Aussagen über den momentanen Zustand möglich sind und bei Abweichungen vom Sollwert geeignete Eingriffe in das System erfolgen können. Damit eine eindeutige Kommunikation möglich wird, sind die in der Messtechnik verwendeten Begriffe, Messverfahren und Maßeinheiten in entsprechenden Normen oder Vorschriften festgelegt.

A van der Waals Equation of State for a Dilute Boson Gas

ERIC Educational Resources Information Center

Deeney, F. A.; O'Leary, J. P.

2012-01-01

An equation of state of a system is a relationship that connects the thermodynamic variables of the system such as pressure and temperature. Such equations are well known for classical gases but less so for quantum systems. In this paper we develop a van der Waals equation of state for a dilute boson gas that may be used to explain the occurrence…

Materials perspective on Casimir and van der Waals interactions

NASA Astrophysics Data System (ADS)

Woods, L. M.; Dalvit, D. A. R.; Tkatchenko, A.; Rodriguez-Lopez, P.; Rodriguez, A. W.; Podgornik, R.

2016-10-01

Interactions induced by electromagnetic fluctuations, such as van der Waals and Casimir forces, are of universal nature present at any length scale between any types of systems. Such interactions are important not only for the fundamental science of materials behavior, but also for the design and improvement of micro- and nanostructured devices. In the past decade, many new materials have become available, which has stimulated the need for understanding their dispersive interactions. The field of van der Waals and Casimir forces has experienced an impetus in terms of developing novel theoretical and computational methods to provide new insights into related phenomena. The understanding of such forces has far reaching consequences as it bridges concepts in materials, atomic and molecular physics, condensed-matter physics, high-energy physics, chemistry, and biology. This review summarizes major breakthroughs and emphasizes the common origin of van der Waals and Casimir interactions. Progress related to novel ab initio modeling approaches and their application in various systems, interactions in materials with Dirac-like spectra, force manipulations through nontrivial boundary conditions, and applications of van der Waals forces in organic and biological matter are examined. The outlook of the review is to give the scientific community a materials perspective of van der Waals and Casimir phenomena and stimulate the development of experimental techniques and applications.

Power Hardware-in-the-Loop Testing of a Smart Distribution System

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

Mendoza Carrillo, Ismael; Breaden, Craig; Medley, Paige

This paper presents the results of the third and final phase of the National Renewable Energy Lab (NREL) INTEGRATE demonstration: Smart Distribution. For this demonstration, high penetrations of solar PV and wind energy systems were simulated in a power hardware-in-the-loop set-up using a smart distribution test feeder. Simulated and real DERs were controlled by a real-time control platform, which manages grid constraints under high clean energy deployment levels. The power HIL testing, conducted at NREL's ESIF smart power lab, demonstrated how dynamically managing DER increases the grid's hosting capacity by leveraging active network management's (ANM) safe and reliable control framework.more » Results are presented for how ANM's real-time monitoring, automation, and control can be used to manage multiple DERs and multiple constraints associated with high penetrations of DER on a distribution grid. The project also successfully demonstrated the importance of escalating control actions given how ANM enables operation of grid equipment closer to their actual physical limit in the presence of very high levels of intermittent DER.« less

An Open Source Extensible Smart Energy Framework

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

Rankin, Linda

Aggregated distributed energy resources are the subject of much interest in the energy industry and are expected to play an important role in meeting our future energy needs by changing how we use, distribute and generate electricity. This energy future includes an increased amount of energy from renewable resources, load management techniques to improve resiliency and reliability, and distributed energy storage and generation capabilities that can be managed to meet the needs of the grid as well as individual customers. These energy assets are commonly referred to as Distributed Energy Resources (DER). DERs rely on a means to communicate informationmore » between an energy provider and multitudes of devices. Today DER control systems are typically vendor-specific, using custom hardware and software solutions. As a result, customers are locked into communication transport protocols, applications, tools, and data formats. Today’s systems are often difficult to extend to meet new application requirements, resulting in stranded assets when business requirements or energy management models evolve. By partnering with industry advisors and researchers, an implementation DER research platform was developed called the Smart Energy Framework (SEF). The hypothesis of this research was that an open source Internet of Things (IoT) framework could play a role in creating a commodity-based eco-system for DER assets that would reduce costs and provide interoperable products. SEF is based on the AllJoynTM IoT open source framework. The demonstration system incorporated DER assets, specifically batteries and smart water heaters. To verify the behavior of the distributed system, models of water heaters and batteries were also developed. An IoT interface for communicating between the assets and a control server was defined. This interface supports a series of “events” and telemetry reporting, similar to those defined by current smart grid communication standards. The results of this effort demonstrated the feasibility and application potential of using IoT frameworks for the creation of commodity-based DER systems. All of the identified commodity-based system requirements were met by the AllJoyn framework. By having commodity solutions, small vendors can enter the market and the cost of implementation for all parties is reduced. Utilities and aggregators can choose from multiple interoperable products reducing the risk of stranded assets. Based on this research it is recommended that interfaces based on existing smart grid communication protocol standards be created for these emerging IoT frameworks. These interfaces should be standardized as part of the IoT framework allowing for interoperability testing and certification. Similarly, IoT frameworks are introducing application level security. This type of security is needed for protecting application and platforms and will be important moving forward. Recommendations are that along with DER-based data model interfaces, platform and application security requirements also be prescribed when IoT devices support DER applications.« less

Effects of intermediates between vitamins K(2) and K(3) on mammalian DNA polymerase inhibition and anti-inflammatory activity.

PubMed

Mizushina, Yoshiyuki; Maeda, Jun; Irino, Yasuhiro; Nishida, Masayuki; Nishiumi, Shin; Kondo, Yasuyuki; Nishio, Kazuyuki; Kuramochi, Kouji; Tsubaki, Kazunori; Kuriyama, Isoko; Azuma, Takeshi; Yoshida, Hiromi; Yoshida, Masaru

2011-02-10

Previously, we reported that vitamin K(3) (VK(3)), but not VK(1) or VK(2) (=MK-4), inhibits the activity of human DNA polymerase γ (pol γ). In this study, we chemically synthesized three intermediate compounds between VK(2) and VK(3), namely MK-3, MK-2 and MK-1, and investigated the inhibitory effects of all five compounds on the activity of mammalian pols. Among these compounds, MK-2 was the strongest inhibitor of mammalian pols α, κ and λ, which belong to the B, Y and X families of pols, respectively; whereas VK(3) was the strongest inhibitor of human pol γ, an A-family pol. MK-2 potently inhibited the activity of all animal species of pol tested, and its inhibitory effect on pol λ activity was the strongest with an IC(50) value of 24.6 μM. However, MK-2 did not affect the activity of plant or prokaryotic pols, or that of other DNA metabolic enzymes such as primase of pol α, RNA polymerase, polynucleotide kinase or deoxyribonuclease I. Because we previously found a positive relationship between pol λ inhibition and anti-inflammatory action, we examined whether these compounds could inhibit inflammatory responses. Among the five compounds tested, MK-2 caused the greatest reduction in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute inflammation in mouse ear. In addition, in a cell culture system using mouse macrophages, MK-2 displayed the strongest suppression of the production of tumor necrosis factor (TNF)-α induced by lipopolysaccharide (LPS). Moreover, MK-2 was found to inhibit the action of nuclear factor (NF)-κB. In an in vivo mouse model of LPS-evoked acute inflammation, intraperitoneal injection of MK-2 in mice led to suppression of TNF-α production in serum. In conclusion, this study has identified VK(2) and VK(3) intermediates, such as MK-2, that are promising anti-inflammatory candidates.

Understanding the Physical and Molecular Basis of Stability of Arabidopsis DNA Pol λ under UV-B and High NaCl Stress

PubMed Central

Das, Kali Pada

2015-01-01

Here, we have investigated the physical and molecular basis of stability of Arabidopsis DNA Pol λ, the sole X family DNA polymerase member in plant genome, under UV-B and salinity stress in connection with the function of the N-terminal BRCT (breast cancer-associated C terminus) domain and Ser-Pro rich region in the regulation of the overall structure of this protein. Tryptophan fluorescence studies, fluorescence quenching and Bis-ANS binding experiments using purified recombinant full length Pol λ and its N-terminal deletion forms have revealed UV-B induced conformational change in BRCT domain deficient Pol λ. On the other hand, the highly conserved C-terminal catalytic core PolX domain maintained its tertiary folds under similar condition. Circular dichroism (CD) and fourier transform infrared (FT-IR) spectral studies have indicated appreciable change in the secondary structural elements in UV-B exposed BRCT domain deficient Pol λ. Increased thermodynamic stability of the C-terminal catalytic core domain suggested destabilizing effect of the N-terminal Ser-Pro rich region on the protein structure. Urea-induced equilibrium unfolding studies have revealed increased stability of Pol λ and its N-terminal deletion mutants at high NaCl concentration. In vivo aggregation studies using transient expression systems in Arabidopsis and tobacco indicated possible aggregation of Pol λ lacking the BRCT domain. Immunoprecipitation assays revealed interaction of Pol λ with the eukaryotic molecular chaperone HSP90, suggesting the possibility of regulation of Pol λ stability by HSP90 in plant cell. Overall, our results have provided one of the first comprehensive information on the biophysical characteristics of Pol λ and indicated the importance of both BRCT and Ser-Pro rich modules in regulating the stability of this protein under genotoxic stress in plants. PMID:26230318

Clustering of Alpers disease mutations and catalytic defects in biochemical variants reveal new features of molecular mechanism of the human mitochondrial replicase, Pol γ

PubMed Central

Euro, Liliya; Farnum, Gregory A.; Palin, Eino; Suomalainen, Anu; Kaguni, Laurie S.

2011-01-01

Mutations in Pol γ represent a major cause of human mitochondrial diseases, especially those affecting the nervous system in adults and in children. Recessive mutations in Pol γ represent nearly half of those reported to date, and they are nearly uniformly distributed along the length of the POLG1 gene (Human DNA Polymerase gamma Mutation Database); the majority of them are linked to the most severe form of POLG syndrome, Alpers–Huttenlocher syndrome. In this report, we assess the structure–function relationships for recessive disease mutations by reviewing existing biochemical data on site-directed mutagenesis of the human, Drosophila and yeast Pol γs, and their homologs from the family A DNA polymerase group. We do so in the context of a molecular model of Pol γ in complex with primer–template DNA, which we have developed based upon the recently solved crystal structure of the apoenzyme form. We present evidence that recessive mutations cluster within five distinct functional modules in the catalytic core of Pol γ. Our results suggest that cluster prediction can be used as a diagnosis-supporting tool to evaluate the pathogenic role of new Pol γ variants. PMID:21824913

Nonlinear state-space modelling of the kinematics of an oscillating circular cylinder in a fluid flow

NASA Astrophysics Data System (ADS)

Decuyper, J.; De Troyer, T.; Runacres, M. C.; Tiels, K.; Schoukens, J.

2018-01-01

The flow-induced vibration of bluff bodies is an important problem of many marine, civil, or mechanical engineers. In the design phase of such structures, it is vital to obtain good predictions of the fluid forces acting on the structure. Current methods rely on computational fluid dynamic simulations (CFD), with a too high computational cost to be effectively used in the design phase or for control applications. Alternative methods use heuristic mathematical models of the fluid forces, but these lack the accuracy (they often assume the system to be linear) or flexibility to be useful over a wide operating range. In this work we show that it is possible to build an accurate, flexible and low-computational-cost mathematical model using nonlinear system identification techniques. This model is data driven: it is trained over a user-defined region of interest using data obtained from experiments or simulations, or both. Here we use a Van der Pol oscillator as well as CFD simulations of an oscillating circular cylinder to generate the training data. Then a discrete-time polynomial nonlinear state-space model is fit to the data. This model relates the oscillation of the cylinder to the force that the fluid exerts on the cylinder. The model is finally validated over a wide range of oscillation frequencies and amplitudes, both inside and outside the so-called lock-in region. We show that forces simulated by the model are in good agreement with the data obtained from CFD.

A universal concept based on cellular neural networks for ultrafast and flexible solving of differential equations.

PubMed

Chedjou, Jean Chamberlain; Kyamakya, Kyandoghere

2015-04-01

This paper develops and validates a comprehensive and universally applicable computational concept for solving nonlinear differential equations (NDEs) through a neurocomputing concept based on cellular neural networks (CNNs). High-precision, stability, convergence, and lowest-possible memory requirements are ensured by the CNN processor architecture. A significant challenge solved in this paper is that all these cited computing features are ensured in all system-states (regular or chaotic ones) and in all bifurcation conditions that may be experienced by NDEs.One particular quintessence of this paper is to develop and demonstrate a solver concept that shows and ensures that CNN processors (realized either in hardware or in software) are universal solvers of NDE models. The solving logic or algorithm of given NDEs (possible examples are: Duffing, Mathieu, Van der Pol, Jerk, Chua, Rössler, Lorenz, Burgers, and the transport equations) through a CNN processor system is provided by a set of templates that are computed by our comprehensive templates calculation technique that we call nonlinear adaptive optimization. This paper is therefore a significant contribution and represents a cutting-edge real-time computational engineering approach, especially while considering the various scientific and engineering applications of this ultrafast, energy-and-memory-efficient, and high-precise NDE solver concept. For illustration purposes, three NDE models are demonstratively solved, and related CNN templates are derived and used: the periodically excited Duffing equation, the Mathieu equation, and the transport equation.

Non-conventional synchronization of weakly coupled active oscillators

NASA Astrophysics Data System (ADS)

Manevitch, L. I.; Kovaleva, M. A.; Pilipchuk, V. N.

2013-03-01

We present a new type of self-sustained vibrations in the fundamental physical model covering a broad area of applications from wave generation in radiophysics and nonlinear optics to the heart muscle contraction and eyesight disorder in biophysics. Such a diversity of applications is due to the universal physical phenomenon of synchronization. Previous studies of this phenomenon, originating from Huygens famous observation, are based mainly on the model of two weakly coupled Van der Pol oscillators and usually deal with their synchronization in the regimes close to nonlinear normal modes (NNMs). In this work, we show for the first time that, in the important case of threshold excitation, an alternative synchronization mechanism can develop when the conventional synchronization becomes impossible. We identify this mechanism as an appearance of dynamic attractor with the complete periodic energy exchange between the oscillators, which is the dissipative analogue of highly intensive beats in a conservative system. This type of motion is therefore opposite to the NNM-type synchronization with no energy exchange by definition. The analytical description of these vibrations employs the concept of Limiting Phase Trajectories (LPTs) introduced by one of the authors earlier for conservative systems. Finally, within the LPT approach, we describe the transition from the complete energy exchange between the oscillators to the energy localization mostly on one of the two oscillators. The localized mode is an attractor in the range of model parameters wherein the LPT as well as the in-phase and out-of-phase NNMs become unstable.

Distributed Coordination of Energy Storage with Distributed Generators

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

Yang, Tao; Wu, Di; Stoorvogel, Antonie A.

2016-07-18

With a growing emphasis on energy efficiency and system flexibility, a great effort has been made recently in developing distributed energy resources (DER), including distributed generators and energy storage systems. This paper first formulates an optimal coordination problem considering constraints at both system and device levels, including power balance constraint, generator output limits, storage energy and power capacity and charging/discharging efficiencies. An algorithm is then proposed to dynamically and automatically coordinate DERs in a distributed manner. With the proposed algorithm, the agent at each DER only maintains a local incremental cost and updates it through information exchange with a fewmore » neighbors, without relying on any central decision maker. Simulation results are used to illustrate and validate the proposed algorithm.« less

Systeme mit veränderlicher Teilchenzahl, Gasentartung

NASA Astrophysics Data System (ADS)

Heintze, Joachim

Bisher haben wir die Zustandsgrößen ν (Zahl der Mole) und N (Zahl der Teilchen im System) als konstant betrachtet. In diesem Kapitel wollen wir untersuchen, wie sich Veränderungen von ν bzw. von N beschreiben lassen. Dazu werden wir eine neue thermodynamische Größe einführen, das chemische Potential μ. Als Beispiele für die Veränderung von Teilchenzahlen werden wir diffusive Prozesse und chemische Reaktionen betrachten. Am Ende des Kapitels werden wir die quantenmechanische Gasentartung diskutieren, bei der das chemische Potential ebenfalls eine Rolle spielt. Wir werden feststellen, dass es nicht schwierig ist, einige Eigenschaften dieses interessanten Materiezustands zu verstehen. Wir behandeln das Thema bereits hier und nicht erst in der Quantenphysik am Ende des Buches, weil es in die Wärmelehre gehört und weil auf dieser Grundlage die elektrischen Eigenschaften von Metallen in Bd. III/9 leicht diskutiert werden können.

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

Dall-Anese, Emiliano; Zhao, Changhong; Guggilam, Swaroop

Power networks have to withstand a variety of disturbances that affect system frequency, and the problem is compounded with the increasing integration of intermittent renewable generation. Following a large-signal generation or load disturbance, system frequency is arrested leveraging primary frequency control provided by governor action in synchronous generators. In this work, we propose a framework for distributed energy resources (DERs) deployed in distribution networks to provide (supplemental) primary frequency response. Particularly, we demonstrate how power-frequency droop slopes for individual DERs can be designed so that the distribution feeder presents a guaranteed frequency-regulation characteristic at the feeder head. Furthermore, the droopmore » slopes are engineered such that injections of individual DERs conform to a well-defined fairness objective that does not penalize them for their location on the distribution feeder. Time-domain simulations for an illustrative network composed of a combined transmission network and distribution network with frequency-responsive DERs are provided to validate the approach.« less

Smart Microgrid Energy Management Controls for Improved Energy Efficiency and Renewables Integration at DoD Installations

DTIC Science & Technology

2013-04-01

products for energy generation, including solar, wind , and gas turbines , energy storage, power conversion, grid integration, and software for...potential security advantages over centralized systems • DER promote fuel diversity (e.g., biomass, landfill gas, flare gas, wind , solar) and...therefore reduce overall energy price volatility • Renewable DER such as wind and solar photovoltaics provide emissions-free energy • DER offer a quicker

Digitalisierung und Energie 4.0 - Wie schaffen wir die digitale Energiewende?

NASA Astrophysics Data System (ADS)

Irlbeck, Maximilian

Die digitale Energiewende verändert nachhaltig die Systeme der "alten" Energiewelt. Ein Zusammenwachsen verschiedener Domänen im Energiesystem, die durch digitale Technologie möglich wird, birgt enorme Herausforderungen, ist aber notwendig, um die Energiewende und ihre Ziele zu meistern. Dieser Beitrag beschreibt die Wirkung der Digitalisierung auf das Energiesystem, listet Charakteristika der digitalen Energiewende auf und schildert für verschiedene Domänen mögliche Zielvorstellungen, die durch digitale Technologie umsetzbar sind. Am Ende erläutert der Beitrag Handlungsschritte, die auf dem Weg zu einem erneuerbaren Energiesystem gegangen werden sollten und zeigt Probleme und Risiken einer Fehlentwicklung auf.

Direct analysis of airborne mite allergen (Der f1) in the residential atmosphere by chemifluorescent immunoassay using bioaerosol sampler.

PubMed

Miyajima, Kumiko; Suzuki, Yurika; Miki, Daisuke; Arai, Moeka; Arakawa, Takahiro; Shimomura, Hiroji; Shiba, Kiyoko; Mitsubayashi, Kohji

2014-06-01

Dermatophagoides farinae allergen (Der f1) is one of the most important indoor allergens associated with allergic diseases in humans. Mite allergen Der f1 is usually associated with particles of high molecular weight; thus, Der f1 is generally present in settled dust. However, a small quantity of Der f1 can be aerosolized and become an airborne component. Until now, a reliable method of detecting airborne Der f1 has not been developed. The aim of this study was to develop a fiber-optic chemifluorescent immunoassay for the detection of airborne Der f1. In this method, the Der f1 concentration measured on the basis of the intensity of fluorescence amplified by an enzymatic reaction between the labeled enzyme by a detection antibody and a fluorescent substrate. The measured Der f1 concentration was in the range from 0.49 to 250 ng/ml and a similar range was found by enzyme-linked immunosorbent assay (ELISA). This method was proved to be highly sensitive to Der f1 compared with other airborne allergens. For the implementation of airborne allergen measurement in a residential environment, a bioaerosol sampler was constructed. The airborne allergen generated by a nebulizer was conveyed to a newly sampler we developed for collecting airborne Der f1. The sampler was composed of polymethyl methacrylate (PMMA) cells for gas/liquid phases and some porous membranes which were sandwiched in between the two phases. Der f1 in air was collected by the sampler and measured using the fiber-optic immunoassay system. The concentration of Der f1 in aerosolized standards was in the range from 0.125 to 2.0 mg/m(3) and the collection rate of the device was approximately 0.2%. © 2013 Elsevier B.V. All rights reserved.

Modelling Framework and the Quantitative Analysis of Distributed Energy Resources in Future Distribution Networks

NASA Astrophysics Data System (ADS)

Han, Xue; Sandels, Claes; Zhu, Kun; Nordström, Lars

2013-08-01

There has been a large body of statements claiming that the large-scale deployment of Distributed Energy Resources (DERs) could eventually reshape the future distribution grid operation in numerous ways. Thus, it is necessary to introduce a framework to measure to what extent the power system operation will be changed by various parameters of DERs. This article proposed a modelling framework for an overview analysis on the correlation between DERs. Furthermore, to validate the framework, the authors described the reference models of different categories of DERs with their unique characteristics, comprising distributed generation, active demand and electric vehicles. Subsequently, quantitative analysis was made on the basis of the current and envisioned DER deployment scenarios proposed for Sweden. Simulations are performed in two typical distribution network models for four seasons. The simulation results show that in general the DER deployment brings in the possibilities to reduce the power losses and voltage drops by compensating power from the local generation and optimizing the local load profiles.

PQScal (Power Quality Score Calculation for Distribution Systems with DER Integration)

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

Power Quality is of great importance to evaluate the “health” of a distribution system, especially when the distributed energy resource (DER) penetration becomes more significant. The individual components that make up power quality, such as voltage magnitude and unbalance, can be measured in simulations or in the field, however, a comprehensive method to incorporate all of these values into a single score doesn't exist. As a result, we propose a methodology to quantify the power quality health using the single number value, named as Power Quality Score (PQS). The PQS is dependent on six metrics that are developed based onmore » both components that directly impact power quality and those are often reference in the context of power quality. These six metrics are named as System Average Voltage Magnitude Violation Index (SAVMVI), System Average Voltage Fluctuation Index (SAVFI), System Average Voltage Unbalance Index (SAVUI), System Control Device Operation Index (SCDOI), System Reactive Power Demand Index (SRPDI) and System Energy Loss Index (SELI). This software tool, PQScal, is developed based on this novel PQS methodology. Besides of traditional distribution systems, PQScal can also measure the power quality for distribution systems with various DER penetrations. PQScal has been tested on two utility distribution feeders with distinct model characteristics and its effectiveness has been proved. In sum, PQScal can help utilities or other parties to measure the power quality of distribution systems with DER integration easily and effectively.« less

The association of TIF-IA and polymerase I mediates promoter recruitment and regulation of ribosomal RNA transcription in Acanthamoeba castellanii.

PubMed

Gogain, Joseph C; Paule, Marvin R

2005-01-01

Large amounts of energy are expended for the construction of the ribosome during both transcription and processing, so it is of utmost importance for the cell to efficiently regulate ribosome production. Understanding how this regulation occurs will provide important insights into cellular growth control and into the coordination of gene expression mediated by all three transcription systems. Ribosomal RNA (rRNA) transcription rates closely parallel the need for protein synthesis; as a cell approaches stationary phase or encounters conditions that negatively affect either growth rate or protein synthesis, rRNA transcription is decreased. In eukaryotes, the interaction of RNA polymerase I (pol I) with the essential transcription initiation factor IA (TIF-IA) has been implicated in this downregulation of transcription. In agreement with the first observation that rRNA transcription is regulated by altering recruitment of pol I to the promoter in Acanthamoeba castellanii, we show here that pol I and an 80-kDa homologue of TIF-IA are found tightly associated in pol I fractions competent for specific transcription. Disruption of the pol I-TIF-IA complex is mediated by a specific dephosphorylation of either pol I or TIF-IA. Phosphatase treatment of TIF-IA-containing A. castellanii pol I fractions results in a downregulation of both transcriptional activity and promoter binding, reminiscent of the inactive pol I fractions purified from encysted cells. The fraction of pol I competent for promoter recruitment is enriched in TIF-IA relative to that not bound by immobilized promoter DNA. This downregulation coincides with an altered electrophoretic mobility of TIF-IA, suggesting at least it is phosphorylated.

Campus Single Sign-On und hochschulübergreifendes Identity Management

NASA Astrophysics Data System (ADS)

Hommel, Wolfgang

Das im Rahmen von IntegraTUM für die TUM geschaffene Identity & Access Management System setzt das Paradigma unified login um, d. h. ein Benutzer kann alle für ihn relevanten Dienste innerhalb der Hochschule mit derselben Loginname-/Passwortkombination nutzen. Dieser Artikel zeigt, wie auf Basis der Software Shibboleth und der deutschlandweiten Hochschulföderation DFN-AAI als weitere Mehrwerte das campusweite web single sign-on und die nahtlose Nutzung zahlreicher externer Web-Anwendungen erreicht werden. Als Beispiel für die Abläufe bei der Erschließung neuer Dienste für die hochschulübergreifende Nutzung wird die Anbindung von Learning Management Systemen auf Basis des DFN-AAI E-Learning-Profils diskutiert. Den umfassenden Vorteilen werden schließlich die aktuellen technischen Grenzen bei der Umsetzung des hochschulübergreifenden Identity Management gegenübergestellt.

Smart Meter Rollout: Intelligente Messsysteme als Schnittstelle zum Kunden im Smart Grid und Smart Market

NASA Astrophysics Data System (ADS)

Vortanz, Karsten; Zayer, Peter

Das Gesetz zur Digitalisierung der Energiewende ist verabschiedet. Ab 2017 sind moderne Messeinrichtungen (mME) und intelligente Messsysteme (iMSys) zu verbauen und zu betreiben. Der "deutsche Weg" für die Einführung von Smart Metern sieht einen stufenweisen Rollout sowie ein Höchstmaß an Informations- und Datensicherheit vor. Dabei spielen iMSys und mME eine wichtige Rolle bei der Neugestaltung der intelligenten Netze (Smart Grids) und des neuen Marktmodells (Smart Market). Dieser Beitrag beschäftigt sich mit den neuen Gesetzen, den Marktrollen und ihren Aufgaben, Datenschutz und Datensicherheit, dem iMSys als sichere Lösung, dem sicheren Betrieb von Smart Meter Gateways, Smart Grid - Smart Market, dem Zusammenspiel zwischen reguliertem Bereich und Markt, den Einsatzbereichen der iMSys sowie den Auswirkungen auf Prozesse und Systeme und gibt Handlungsempfehlungen.

Naval Research Logistics Quarterly. Volume 28, Number 4,

DTIC Science & Technology

1981-12-01

Fan [31 and an observation by Meijerink and van der Vorst [181 guarantee that after pivoting on any diagonal element of a diagonally dominant M- matrix...Science, 3, 255-269 (1957). 1181 Meijerink, J. and H. Van der Vorst, "An Iterative Solution Method for Linear Systems of which the Coefficient Matrix Is a...Hee, K., A. Hordijk and J. Van der Wal, "Successive Approximations for Convergent Dynamic Programming," in Markov Decision Theory, H. Tijms and J

Materials perspective on Casimir and van der Waals interactions

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

Woods, L. M.; Dalvit, D. A. R.; Tkatchenko, A.

Interactions induced by electromagnetic fluctuations, such as van der Waals and Casimir forces, are of universal nature present at any length scale between any types of systems. In such interactions these are important not only for the fundamental science of materials behavior, but also for the design and improvement of micro- and nanostructured devices. In the past decade, many new materials have become available, which has stimulated the need for understanding their dispersive interactions. The field of van der Waals and Casimir forces has experienced an impetus in terms of developing novel theoretical and computational methods to provide new insightsmore » into related phenomena. The understanding of such forces has far reaching consequences as it bridges concepts in materials, atomic and molecular physics, condensed-matter physics, high-energy physics, chemistry, and biology. Our review summarizes major breakthroughs and emphasizes the common origin of van der Waals and Casimir interactions. Progress related to novel ab initio modeling approaches and their application in various systems, interactions in materials with Dirac-like spectra, force manipulations through nontrivial boundary conditions, and applications of van der Waals forces in organic and biological matter are examined. Finally, the outlook of the review is to give the scientific community a materials perspective of van der Waals and Casimir phenomena and stimulate the development of experimental techniques and applications.« less

Materials perspective on Casimir and van der Waals interactions

DOE PAGES

Woods, L. M.; Dalvit, D. A. R.; Tkatchenko, A.; ...

2016-11-02

Interactions induced by electromagnetic fluctuations, such as van der Waals and Casimir forces, are of universal nature present at any length scale between any types of systems. In such interactions these are important not only for the fundamental science of materials behavior, but also for the design and improvement of micro- and nanostructured devices. In the past decade, many new materials have become available, which has stimulated the need for understanding their dispersive interactions. The field of van der Waals and Casimir forces has experienced an impetus in terms of developing novel theoretical and computational methods to provide new insightsmore » into related phenomena. The understanding of such forces has far reaching consequences as it bridges concepts in materials, atomic and molecular physics, condensed-matter physics, high-energy physics, chemistry, and biology. Our review summarizes major breakthroughs and emphasizes the common origin of van der Waals and Casimir interactions. Progress related to novel ab initio modeling approaches and their application in various systems, interactions in materials with Dirac-like spectra, force manipulations through nontrivial boundary conditions, and applications of van der Waals forces in organic and biological matter are examined. Finally, the outlook of the review is to give the scientific community a materials perspective of van der Waals and Casimir phenomena and stimulate the development of experimental techniques and applications.« less

Effects of Active Site Mutations on Specificity of Nucleobase Binding in Human DNA Polymerase η.

PubMed

Ucisik, Melek N; Hammes-Schiffer, Sharon

2017-04-20

Human DNA polymerase η (Pol η) plays a vital role in protection against skin cancer caused by damage from ultraviolet light. This enzyme rescues stalled replication forks at cyclobutane thymine-thymine dimers (TTDs) by inserting nucleotides opposite these DNA lesions. Residue R61 is conserved in the Pol η enzymes across species, but the corresponding residue, as well as its neighbor S62, is different in other Y-family polymerases, Pol ι and Pol κ. Herein, R61 and S62 are mutated to their Pol ι and Pol κ counterparts. Relative binding free energies of dATP to mutant Pol η•DNA complexes with and without a TTD were calculated using thermodynamic integration. The binding free energies of dATP to the Pol η•DNA complex with and without a TTD are more similar for all of these mutants than for wild-type Pol η, suggesting that these mutations decrease the ability of this enzyme to distinguish between a TTD lesion and undamaged DNA. Molecular dynamics simulations of the mutant systems provide insights into the molecular level basis for the changes in relative binding free energies. The simulations identified differences in hydrogen-bonding, cation-π, and π-π interactions of the side chains with the dATP and the TTD or thymine-thymine (TT) motif. The simulations also revealed that R61 and Q38 act as a clamp to position the dATP and the TTD or TT and that the mutations impact the balance among the interactions related to this clamp. Overall, these calculations suggest that R61 and S62 play key roles in the specificity and effectiveness of Pol η for bypassing TTD lesions during DNA replication. Understanding the basis for this specificity is important for designing drugs aimed at cancer treatment.

Effects of Active Site Mutations on Specificity of Nucleobase Binding in Human DNA Polymerase η

PubMed Central

2016-01-01

Human DNA polymerase η (Pol η) plays a vital role in protection against skin cancer caused by damage from ultraviolet light. This enzyme rescues stalled replication forks at cyclobutane thymine–thymine dimers (TTDs) by inserting nucleotides opposite these DNA lesions. Residue R61 is conserved in the Pol η enzymes across species, but the corresponding residue, as well as its neighbor S62, is different in other Y-family polymerases, Pol ι and Pol κ. Herein, R61 and S62 are mutated to their Pol ι and Pol κ counterparts. Relative binding free energies of dATP to mutant Pol η•DNA complexes with and without a TTD were calculated using thermodynamic integration. The binding free energies of dATP to the Pol η•DNA complex with and without a TTD are more similar for all of these mutants than for wild-type Pol η, suggesting that these mutations decrease the ability of this enzyme to distinguish between a TTD lesion and undamaged DNA. Molecular dynamics simulations of the mutant systems provide insights into the molecular level basis for the changes in relative binding free energies. The simulations identified differences in hydrogen-bonding, cation−π, and π–π interactions of the side chains with the dATP and the TTD or thymine–thymine (TT) motif. The simulations also revealed that R61 and Q38 act as a clamp to position the dATP and the TTD or TT and that the mutations impact the balance among the interactions related to this clamp. Overall, these calculations suggest that R61 and S62 play key roles in the specificity and effectiveness of Pol η for bypassing TTD lesions during DNA replication. Understanding the basis for this specificity is important for designing drugs aimed at cancer treatment. PMID:28423907

Nutrient/TOR-dependent regulation of RNA polymerase III controls tissue and organismal growth in Drosophila

PubMed Central

Marshall, Lynne; Rideout, Elizabeth J; Grewal, Savraj S

2012-01-01

The nutrient/target-of-rapamycin (TOR) pathway has emerged as a key regulator of tissue and organismal growth in metazoans. The signalling components of the nutrient/TOR pathway are well defined; however, the downstream effectors are less understood. Here, we show that the control of RNA polymerase (Pol) III-dependent transcription is an essential target of TOR in Drosophila. We find that TOR activity controls Pol III in growing larvae via inhibition of the repressor Maf1 and, in part, via the transcription factor Drosophila Myc (dMyc). Moreover, we show that loss of the Pol III factor, Brf, leads to reduced tissue and organismal growth and prevents TOR-induced cellular growth. TOR activity in the larval fat body, a tissue equivalent to vertebrate fat or liver, couples nutrition to insulin release from the brain. Accordingly, we find that fat-specific loss of Brf phenocopies nutrient limitation and TOR inhibition, leading to decreased systemic insulin signalling and reduced organismal growth. Thus, stimulation of Pol III is a key downstream effector of TOR in the control of cellular and systemic growth. PMID:22367393

Dynamic Power Distribution System Management With a Locally Connected Communication Network

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

Dall-Anese, Emiliano; Zhang, Kaiqing; Basar, Tamer

Coordinated optimization and control of distribution-level assets can enable a reliable and optimal integration of massive amount of distributed energy resources (DERs) and facilitate distribution system management (DSM). Accordingly, the objective is to coordinate the power injection at the DERs to maintain certain quantities across the network, e.g., voltage magnitude, line flows, or line losses, to be close to a desired profile. By and large, the performance of the DSM algorithms has been challenged by two factors: i) the possibly non-strongly connected communication network over DERs that hinders the coordination; ii) the dynamics of the real system caused by themore » DERs with heterogeneous capabilities, time-varying operating conditions, and real-time measurement mismatches. In this paper, we investigate the modeling and algorithm design and analysis with the consideration of these two factors. In particular, a game theoretic characterization is first proposed to account for a locally connected communication network over DERs, along with the analysis of the existence and uniqueness of the Nash equilibrium (NE) therein. To achieve the equilibrium in a distributed fashion, a projected-gradient-based asynchronous DSM algorithm is then advocated. The algorithm performance, including the convergence speed and the tracking error, is analytically guaranteed under the dynamic setting. Extensive numerical tests on both synthetic and realistic cases corroborate the analytical results derived.« less

[Homöopathisch-phytotherapeutische Behandlung des Reizdarmsyndroms mit Magen-Darm-Entoxin N®: Eine Anwendungsbeobachtung].

PubMed

Märtens, Diane; Range, Natasha; Günnewich, Nils; Gruber, Nicola; Schmidt, Stefan

Hintergrund: In dieser Anwendungsbeobachtung wird zum ersten Mal die Behandlung des Reizdarmsyndroms (RDS) mit einem homöopathisch-phytotherapeutischen Komplexpräparat beschrieben. Methodik: Ziel der 6-wöchigen Therapie mit dem Magen-Darm-Entoxin N® war die Reduzierung der RDS-Symptomatik sowie die Verbesserung der Lebensqualität. Zielkriterien waren die Veränderungen in der Irritable Bowel Syndrome - Severity Scoring System (IBS-SSS) und der Irritable Bowel Syndrome - Quality-of-Life Scale (IBS-QoL). Die Patient/innen (N = 41; Alter 44,0 ± 15,74 Jahre) wurden zu gleichen Teilen in einer Hausarztpraxis (N = 20) und einer Heilpraktikerpraxis (N = 21) rekrutiert. Ergebnisse: Der IBS-QoL-Score verringerte sich signifikant (prä: 35,9 ± 16,3; post: 20,1 ± 13,4; t = 8,504; p < 0,001). Die Effektstärke betrug 1,34 (Cohens d). Der IBS-SSS-Score verringerte sich ebenfalls signifikant (prä: 239,4 ± 83,4; post: 123,7 ± 80,9; t = 7,825; p < 0,001) mit einer Effektstärke von d = 1,24. Die Neben- und Wechselwirkungen waren minimal und signifikante Unterschiede zwischen beiden Praxen wurden nicht gefunden. Schlussfolgerungen: Magen-Darm-Entoxin N® ist eine sichere und sinnvolle Therapieoption bei der Behandlung des RDS. Allerdings sollten randomisierte kontrollierte Studien folgen, um die Spezifizität der Ergebnisse dieser Anwendungsbeobachtung zu stützen. © 2017 S. Karger GmbH, Freiburg.

A Genetic Selection for dinB Mutants Reveals an Interaction between DNA Polymerase IV and the Replicative Polymerase That Is Required for Translesion Synthesis.

PubMed

Scotland, Michelle K; Heltzel, Justin M H; Kath, James E; Choi, Jung-Suk; Berdis, Anthony J; Loparo, Joseph J; Sutton, Mark D

2015-09-01

Translesion DNA synthesis (TLS) by specialized DNA polymerases (Pols) is a conserved mechanism for tolerating replication blocking DNA lesions. The actions of TLS Pols are managed in part by ring-shaped sliding clamp proteins. In addition to catalyzing TLS, altered expression of TLS Pols impedes cellular growth. The goal of this study was to define the relationship between the physiological function of Escherichia coli Pol IV in TLS and its ability to impede growth when overproduced. To this end, 13 novel Pol IV mutants were identified that failed to impede growth. Subsequent analysis of these mutants suggest that overproduced levels of Pol IV inhibit E. coli growth by gaining inappropriate access to the replication fork via a Pol III-Pol IV switch that is mechanistically similar to that used under physiological conditions to coordinate Pol IV-catalyzed TLS with Pol III-catalyzed replication. Detailed analysis of one mutant, Pol IV-T120P, and two previously described Pol IV mutants impaired for interaction with either the rim (Pol IVR) or the cleft (Pol IVC) of the β sliding clamp revealed novel insights into the mechanism of the Pol III-Pol IV switch. Specifically, Pol IV-T120P retained complete catalytic activity in vitro but, like Pol IVR and Pol IVC, failed to support Pol IV TLS function in vivo. Notably, the T120P mutation abrogated a biochemical interaction of Pol IV with Pol III that was required for Pol III-Pol IV switching. Taken together, these results support a model in which Pol III-Pol IV switching involves interaction of Pol IV with Pol III, as well as the β clamp rim and cleft. Moreover, they provide strong support for the view that Pol III-Pol IV switching represents a vitally important mechanism for regulating TLS in vivo by managing access of Pol IV to the DNA.

Surface roughness of novel resin composites polished with one-step systems.

PubMed

Ergücü, Z; Türkün, L S

2007-01-01

This study: 1) analyzed the surface roughness of five novel resin composites that contain nanoparticles after polishing with three different one-step systems and 2) evaluated the effectiveness of these polishers and their possible surface damage using scanning electron microscope (SEM) analysis. The resin composites evaluated in this study include CeramX, Filtek Supreme XT, Grandio, Premise and Tetric EvoCeram. A total of 100 discs (20/resin composites, 10 x 2 mm) were fabricated. Five specimens/resin composites cured under Mylar strips served as the control. The samples were polished for 30 seconds with PoGo, OptraPol and One Gloss discs at 15,000 rpm using a slow speed handpiece. The surfaces were tested for roughness (Ra) with a surface roughness tester and examined with SEM. One-way ANOVA was used for statistical analysis (p = 0.05). For all the composites tested, differences between the polishing systems were found to be significant (p < 0.05). For Filtek Supreme XT, Mylar and PoGo created equally smooth surfaces, while significantly rougher surfaces were obtained after OptraPol and One Gloss applications. For Grandio, Mylar and PoGo created equally smooth surfaces, while OptraPol and One Gloss produced equally rougher surfaces. Tetric EvoCeram exhibited the roughest surface with OptraPol, while no significant differences were found between Premise and CeramX. According to SEM images, OptraPol and One Gloss scratched and plucked the particles away from the surface, while PoGo created a uniform finish, although the roughness values were not the same for each composite. Effectiveness of the polishers seems to be material dependent.

Spacesuit Integrated Carbon Nanotube Dust Mitigation System for Lunar Exploration

NASA Astrophysics Data System (ADS)

Manyapu, Kavya Kamal

Lunar dust proved to be troublesome during the Apollo missions. The lunar dust comprises of fine particles, with electric charges imparted by solar winds and ultraviolet radiation. As such, it adheres readily, and easily penetrates through smallest crevices into mechanisms. During Apollo missions, the powdery dust substantially degraded the performance of spacesuits by abrading suit fabric and clogging seals. Dust also degraded other critical equipment such as rovers, thermal control and optical surfaces, solar arrays, and was thus shown to be a major issue for surface operations. Even inside the lunar module, Apollo astronauts were exposed to this dust when they removed their dust coated spacesuits. This historical evidence from the Apollo missions has compelled NASA to identify dust mitigation as a critical path. This important environmental challenge must be overcome prior to sending humans back to the lunar surface and potentially to other surfaces such as Mars and asteroids with dusty environments. Several concepts were successfully investigated by the international research community for preventing deposition of lunar dust on rigid surfaces (ex: solar cells, thermal radiators). However, applying these technologies for flexible surfaces and specifically to spacesuits has remained an open challenge, due to the complexity of the suit design, geometry, and dynamics. The research presented in this dissertation brings original contribution through the development and demonstration of the SPacesuit Integrated Carbon nanotube Dust Ejection/Removal (SPIcDER) system to protect spacesuits and other flexible surfaces from lunar dust. SPIcDER leverages the Electrodynamic Dust Shield (EDS) concept developed at NASA for use on solar cells. For the SPIcDER research, the EDS concept is customized for application on spacesuits and flexible surfaces utilizing novel materials and specialized design techniques. Furthermore, the performance of the active SPIcDER system is enhanced by integrating a passive technique based on Work Function Matching coating. SPIcDER aims for a self-cleaning spacesuit that can repel lunar dust. The SPIcDER research encompassed numerous demonstrations on coupons made of spacesuit outerlayer fabric, to validate the feasibility of the concept, and provide evidence that the SPIcDER system is capable of repelling over 85% of lunar dust simulant comprising of particles in the range of 10 microm-75microm, in ambient and vacuum conditions. Furthermore, the research presented in this dissertation proves the scalability of the SPIcDER technology on a full scale functional prototype of a spacesuit knee joint-section, and demonstrates its scaled functionality and performance using lunar dust simulant. It also comprises detailed numerical simulation and parametric analysis in ANSYS Maxwell and MATLAB for optimizing the integration of the SPIcDER system into the spacesuit outerlayer. The research concludes with analysis and experimental results on design, manufacturability, operational performance, practicality of application and astronaut safety. The research aims primarily towards spacesuit dust contamination. The SPIcDER technology developed in this research is however versatile, that can be optimized to a wide range of flexible surfaces for space and terrain applications-such as exploration missions to asteroids, Mars and dust-prone applications on Earth.

Transactive System: Part I: Theoretical Underpinnings of Payoff Functions, Control Decisions, Information Privacy, and Solution Concepts

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

Lian, Jianming; Zhang, Wei; Sun, Y.

The increased penetration of renewable energy has significantly changed the conditions and the operational timing of the electricity grid. More flexible, faster ramping resources are needed to compensate for the uncertainty and variability introduced by renewable energy. Distributed energy resources (DERs) such as distributed generators, energy storage, and controllable loads could help manage the power grid in terms of both economic efficiency and operational reliability. In order to realize the benefits of DERs, coordination and control approaches must be designed to enable seamless integration of DERs into the power grid. Transactive coordination and control is a new approach for DERmore » integration, where individual resources are automated and engaged through market interaction. Transactive approaches use economic signals—prices or incentives—to engage DERs. These economic signals must reflect the true value of the DER contributions, so that they seamlessly and equitably compete for the opportunities that today are only available to grid-owned assets. Value signals must be communicated to the DERs in near-real time, the assets must be imbued with new forms of distributed intelligence and control to take advantage of the opportunities presented by these signals, and they must be capable of negotiating and transacting a range of market-driven energy services. The concepts of transactive energy systems are not new, but build upon evolutionary economic changes in financial and electric power markets. These concepts also recognize the different regional structures of wholesale power markets, electricity delivery markets, retail markets, and vertically integrated service provider markets. Although transactive energy systems are not revolutionary, they will be transformational in their ability to provide flexibility and operational efficiency. A main goal of this research is to establish useful foundation for analysis of transactive energy systems and to facilitate new transactive energy system design with demonstrable guarantees on stability and performance. Specifically, the goals are to (1) establish a theoretical basis for evaluating the performance of different transactive systems, (2) devise tools to address canonical problems that exemplify challenges and scenarios of transactive systems, and (3) provide guidelines for design of future transactive systems. This report, Part 1 of a two part series, advances the above-listed research objectives by reviewing existing transactive systems and identifying a theoretical foundation that integrates payoff functions, control decisions, information privacy, and mathematical solution concepts.« less

Research on Multi-Temporal PolInSAR Modeling and Applications

NASA Astrophysics Data System (ADS)

Hong, Wen; Pottier, Eric; Chen, Erxue

2014-11-01

In the study of theory and processing methodology, we apply accurate topographic phase to the Freeman-Durden decomposition for PolInSAR data. On the other hand, we present a TomoSAR imaging method based on convex optimization regularization theory. The target decomposition and reconstruction performance will be evaluated by multi-temporal Land P-band fully polarimetric images acquired in BioSAR campaigns. In the study of hybrid Quad-Pol system performance, we analyse the expression of range ambiguity to signal ratio (RASR) in this architecture. Simulations are used to testify its advantage in the improvement of range ambiguities.

Research on Multi-Temporal PolInSAR Modeling and Applications

NASA Astrophysics Data System (ADS)

Hong, Wen; Pottier, Eric; Chen, Erxue

2014-11-01

In the study of theory and processing methodology, we apply accurate topographic phase to the Freeman- Durden decomposition for PolInSAR data. On the other hand, we present a TomoSAR imaging method based on convex optimization regularization theory. The target decomposition and reconstruction performance will be evaluated by multi-temporal L- and P-band fully polarimetric images acquired in BioSAR campaigns. In the study of hybrid Quad-Pol system performance, we analyse the expression of range ambiguity to signal ratio (RASR) in this architecture. Simulations are used to testify its advantage in the improvement of range ambiguities.

Comparison of permutationally invariant polynomials, neural networks, and Gaussian approximation potentials in representing water interactions through many-body expansions

NASA Astrophysics Data System (ADS)

Nguyen, Thuong T.; Székely, Eszter; Imbalzano, Giulio; Behler, Jörg; Csányi, Gábor; Ceriotti, Michele; Götz, Andreas W.; Paesani, Francesco

2018-06-01

The accurate representation of multidimensional potential energy surfaces is a necessary requirement for realistic computer simulations of molecular systems. The continued increase in computer power accompanied by advances in correlated electronic structure methods nowadays enables routine calculations of accurate interaction energies for small systems, which can then be used as references for the development of analytical potential energy functions (PEFs) rigorously derived from many-body (MB) expansions. Building on the accuracy of the MB-pol many-body PEF, we investigate here the performance of permutationally invariant polynomials (PIPs), neural networks, and Gaussian approximation potentials (GAPs) in representing water two-body and three-body interaction energies, denoting the resulting potentials PIP-MB-pol, Behler-Parrinello neural network-MB-pol, and GAP-MB-pol, respectively. Our analysis shows that all three analytical representations exhibit similar levels of accuracy in reproducing both two-body and three-body reference data as well as interaction energies of small water clusters obtained from calculations carried out at the coupled cluster level of theory, the current gold standard for chemical accuracy. These results demonstrate the synergy between interatomic potentials formulated in terms of a many-body expansion, such as MB-pol, that are physically sound and transferable, and machine-learning techniques that provide a flexible framework to approximate the short-range interaction energy terms.

Singular Hopf bifurcation in a differential equation with large state-dependent delay.

PubMed

Kozyreff, G; Erneux, T

2014-02-08

We study the onset of sustained oscillations in a classical state-dependent delay (SDD) differential equation inspired by control theory. Owing to the large delays considered, the Hopf bifurcation is singular and the oscillations rapidly acquire a sawtooth profile past the instability threshold. Using asymptotic techniques, we explicitly capture the gradual change from nearly sinusoidal to sawtooth oscillations. The dependence of the delay on the solution can be either linear or nonlinear, with at least quadratic dependence. In the former case, an asymptotic connection is made with the Rayleigh oscillator. In the latter, van der Pol's equation is derived for the small-amplitude oscillations. SDD differential equations are currently the subject of intense research in order to establish or amend general theorems valid for constant-delay differential equation, but explicit analytical construction of solutions are rare. This paper illustrates the use of singular perturbation techniques and the unusual way in which solvability conditions can arise for SDD problems with large delays.

Arm motion coupling during locomotion-like actions: An experimental study and a dynamic model

PubMed Central

Shapkova, E.Yu; Terekhov, A.V.; Latash, M.L.

2010-01-01

We studied the coordination of arm movements in standing persons who performed an out-of-phase arm-swinging task while stepping in place or while standing. The subjects were instructed to stop one of the arms in response to an auditory signal while trying to keep the rest of the movement pattern unchanged. A significant increase was observed in the amplitude of the arm that continued swinging under both the stepping and standing conditions. This increase was similar between the right and left arms. A dynamic model was developed including two coupled non-linear van der Pol oscillators. We assumed that stopping an arm did not eliminate the coupling but introduced a new constraint. Within the model, superposition of two factors, a command to stop the ongoing movement of one arm and the coupling between the two oscillators, has been able to account for the observed effects. The model makes predictions for future experiments. PMID:21628725

On the Origin of Pulsations of Sub-THz Emission from Solar Flares

NASA Astrophysics Data System (ADS)

Zaitsev, V. V.; Stepanov, A. V.; Kaufmann, P.

2014-08-01

We propose a model to explain fast pulsations in sub-THz emission from solar flares. The model is based on the approach of a flaring loop as an equivalent electric circuit and explains the pulse-repetition rate, the high-quality factor, Q≥103, low modulation depth, pulse synchronism at different frequencies, and the dependence of the pulse-repetition rate on the emission flux, observed by Kaufmann et al. ( Astrophys. J. 697, 420, 2009). We solved the nonlinear equation for electric current oscillations using a Van der Pol method and found the steady-state value for the amplitude of the current oscillations. Using the pulse rate variation during the flare on 4 November 2003, we found a decrease of the electric current from 1.7×1012 A in the flare maximum to 4×1010 A just after the burst. Our model is consistent with the plasma mechanism of sub-THz emission suggested recently by Zaitsev, Stepanov, and Melnikov ( Astron. Lett. 39, 650, 2013).

A plasmid-based reverse genetics system for influenza A virus.

PubMed Central

Pleschka, S; Jaskunas, R; Engelhardt, O G; Zürcher, T; Palese, P; García-Sastre, A

1996-01-01

A reverse genetics system for negative-strand RNA viruses was first successfully developed for influenza viruses. This technology involved the transfection of in vitro-reconstituted ribonucleoprotein (RNP) complexes into influenza virus-infected cells. We have now developed a method that allows intracellular reconstitution of RNP complexes from plasmid-based expression vectors. Expression of a viral RNA-like transcript is achieved from a plasmid containing a truncated human polymerase I (polI) promoter and a ribozyme sequence that generates the desired 3' end by autocatalytic cleavage. The polI-driven plasmid is cotransfected into human 293 cells with polII-responsive plasmids that express the viral PB1, PB2, PA, and NP proteins. This exclusively plasmid-driven system results in the efficient transcription and replication of the viral RNA-like reporter and allows the study of cis- and trans-acting signals involved in the transcription and replication of influenza virus RNAs. Using this system, we have also been able to rescue a synthetic neuraminidase gene into a recombinant influenza virus. This method represents a convenient alternative to the previously established RNP transfection system. PMID:8648766

A review on data and predictions of water dielectric spectra for calculations of van der Waals surface forces.

PubMed

Wang, Jianlong; Nguyen, Anh V

2017-12-01

Van der Waals forces are one of the important components of intermolecular, colloidal and surface forces governing many phenomena and processes. The latest examples include the colloidal interactions between hydrophobic colloids and interfaces in ambient (non-degassed) water in which dissolved gases and nanobubbles are shown to affect the van der Waals attractions significantly. The advanced computation of van der Waals forces in aqueous systems by the Lifshitz theory requires reliable data for water dielectric spectra. In this paper we review the available predictions of water dielectric spectra for calculating colloidal and surface van der Waals forces. Specifically, the available experimental data for the real and imaginary parts of the complex dielectric function of liquid water in the microwave, IR and UV regions and various corresponding predictions of the water spectra are critically reviewed. The data in the UV region are critical, but the available predictions are still based on the outdated data obtained in 1974 (for frequency only up to 25.5eV). We also reviewed and analysed the experimental data obtained for the UV region in 2000 (for frequency up to 50eV) and 2015 (for frequency up to 100eV). The 1974 and 2000 data require extrapolations to higher frequencies needed for calculating the van der Waals forces but remain inaccurate. Our analysis shows that the latest data of 2015 do not require the extrapolation and can be used to reliably calculate van der Waals forces. The most recent water dielectric spectra gives the (non-retarded) Hamaker constant, A=5.20×10 -20 J, for foam films of liquid water. This review provides the most updated and reliable water dielectric spectra to compute van der Waals forces in aqueous systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of an immunomodulatory Der p 2-FIP-fve fusion protein produced in transformed rice suspension cell culture.

PubMed

Su, Chin-Fen; Kuo, I-Chun; Chen, Peng-Wen; Huang, Chiung-Hui; Seow, See Voon; Chua, Kaw Yan; Yu, Su-May

2012-02-01

Der p 2, a major allergen of Dermatophagoides pteronyssinus mites, is one of the most clinically relevant allergens to allergic patients worldwide. FIP-fve protein (Fve) from the golden needle mushroom (Flammulina velutipes) is an immunomodulatory protein with potential Th1-skewed adjuvant properties. Here, we produced and immunologically evaluated a Der p 2-Fve fusion protein as a potential immunotherapeutic for allergic diseases. Using an inducible expression system in cultured rice suspension cells, the recombinant Der p 2-Fve fusion protein (designated as OsDp2Fve) was expressed in rice cells under the control of an α-amylase gene (αAmy8) promoter and secreted under sucrose starvation. OsDp2Fve was partially purified from the cultured medium. The conformation of Der p 2 in OsDp2Fve remains intact as reflected by its unaltered allergenicity, as assessed by human IgE ELISA and histamine release assays, compared to non-fusion Der p 2 protein. Furthermore, the Fve protein expressed in OsDp2Fve retains its in vitro lymphoproliferative activity but loses its hemagglutination and lymphoagglutination effects compared to the native protein. Notably, in vivo evaluation showed that mice administered with OsDp2Fve possessed an enhanced production of Der p 2-specific IgG antibodies without potentiating the production of Der p 2-specific IgE and Th2 effector cytokines in comparison with mice co-administered with native Fve and Der p 2 proteins. These results suggest that the recombinant Der p 2-Fve fusion protein produced in rice suspension cell cultures has a great potential for allergy immunotherapy.

Magnetisches Tracking für die Navigation mit dem da Vinci® Surgical System

NASA Astrophysics Data System (ADS)

Nickel, Felix; Wegner, Ingmar; Kenngott, Hannes; Neuhaus, Jochen; Müller-Stich, Beat P.; Meinzer, Hans-Peter; Gutt, Carsten N.

In dieser Studie wurde untersucht ob in einem typischen OP-Aufbau mit dem da Vinci® Telemanipulator elektromagnetisches Tracking für die Realisation eines Navigationssystems eingesetzt werden kann. Hierfür wurde in einem realen OP-Aufbau untersucht, wie stark metallische und ferromagnetisch wirksame Objekte wie Operationstisch und Telemanipulator das elektromagnetische Feld des Trackingsystems beeinflussen. Die Ergebnisse zeigen, dass der Telemanipulator nur unwesentlich die Störung des Magnetfeldes durch den OP-Tisch verstärkt. Insbesondere die Bewegung der Instrumente im Trackingvolumen verursachte keine zusätzliche relevante Störung des Magnetfeldes. Bei Begrenzung des Trackingvolumens auf eine Länge von 190 mm, Höhe von 200mm und Breite von 400 mm war der maximale Fehler in diesem Bereich an allen Messpunkten kleiner 10 mm. Der Einsatz von elektromagnetischem Tracking für die Navigation mit dem da Vinci® Surgical System ist somit in einem begrenzten Arbeitsvolumen mit hinreichender Genauigkeit möglich.

Effective field theories for van der Waals interactions

NASA Astrophysics Data System (ADS)

Brambilla, Nora; Shtabovenko, Vladyslav; Tarrús Castellà, Jaume; Vairo, Antonio

2017-06-01

Van der Waals interactions between two neutral but polarizable systems at a separation R much larger than the typical size of the systems are at the core of a broad sweep of contemporary problems in settings ranging from atomic, molecular and condensed matter physics to strong interactions and gravity. In this paper, we reexamine the dispersive van der Waals interactions between two hydrogen atoms. The novelty of the analysis resides in the usage of nonrelativistic effective field theories of quantum electrodynamics. In this framework, the van der Waals potential acquires the meaning of a matching coefficient in an effective field theory, dubbed van der Waals effective field theory, suited to describe the low-energy dynamics of an atom pair. It may be computed systematically as a series in R times some typical atomic scale and in the fine-structure constant α . The van der Waals potential gets short-range contributions and radiative corrections, which we compute in dimensional regularization and renormalize here for the first time. Results are given in d space-time dimensions. One can distinguish among different regimes depending on the relative size between 1 /R and the typical atomic bound-state energy, which is of order m α2. Each regime is characterized by a specific hierarchy of scales and a corresponding tower of effective field theories. The short-distance regime is characterized by 1 /R ≫m α2 and the leading-order van der Waals potential is the London potential. We also compute next-to-next-to-next-to-leading-order corrections. In the long-distance regime we have 1 /R ≪m α2. In this regime, the van der Waals potential contains contact terms, which are parametrically larger than the Casimir-Polder potential that describes the potential at large distances. In the effective field theory, the Casimir-Polder potential counts as a next-to-next-to-next-to-leading-order effect. In the intermediate-distance regime, 1 /R ˜m α2, a significantly more complex potential is obtained. We compare this exact result with the two previous limiting cases. We conclude by commenting on the van der Waals interactions in the hadronic case.

Electrostatically frequency tunable micro-beam-based piezoelectric fluid flow energy harvester

NASA Astrophysics Data System (ADS)

Rezaee, Mousa; Sharafkhani, Naser

2017-07-01

This research investigates the dynamic behavior of a sandwich micro-beam based piezoelectric energy harvester with electrostatically adjustable resonance frequency. The system consists of a cantilever micro-beam immersed in a fluid domain and is subjected to the simultaneous action of cross fluid flow and nonlinear electrostatic force. Two parallel piezoelectric laminates are extended along the length of the micro-beam and connected to an external electric circuit which generates an output power as a result of the micro-beam oscillations. The fluid-coupled structure is modeled using Euler-Bernoulli beam theory and the equivalent force terms for the fluid flow. Fluid induced forces comprise the added inertia force which is evaluated using equivalent added mass and the drag and lift forces which are evaluated using relative velocity and Van der Pol equation. In addition to flow velocity and fluid density, the influence of several design parameters such as external electrical resistance, piezo layer position, and dc voltage on the generated power are investigated by using Galerkin and step by step linearization method. It is shown that for given flowing fluid parameters, i.e., density and velocity, one can adjust the applied dc voltage to tune resonance frequency so that the lock-in phenomenon with steady large amplitude oscillations happens, also by adjusting the harvester parameters including the mechanical and electrical ones, the maximal output power of the harvester becomes possible.

Developing the Polish Educational Needs Assessment Tool (Pol-ENAT) in rheumatoid arthritis and systemic sclerosis: a cross-cultural validation study using Rasch analysis.

PubMed

Sierakowska, Matylda; Sierakowski, Stanisław; Sierakowska, Justyna; Horton, Mike; Ndosi, Mwidimi

2015-03-01

To undertake cross-cultural adaptation and validation of the educational needs assessment tool (ENAT) for use with people with rheumatoid arthritis (RA) and systemic sclerosis (SSc) in Poland. The study involved two main phases: (1) cross-cultural adaptation of the ENAT from English into Polish and (2) Cross-cultural validation of Polish Educational Needs Assessment Tool (Pol-ENAT). The first phase followed an established process of cross-cultural adaptation of self-report measures. The second phase involved completion of the Pol-ENAT by patients and subjecting the data to Rasch analysis to assess the construct validity, unidimensionality, internal consistency and cross-cultural invariance. An adequate conceptual equivalence was achieved following the adaptation process. The dataset for validation comprised a total of 278 patients, 237 (85.3 %) of which were female. In each disease group (145, RA and 133, SSc), the 7 domains of the Pol-ENAT were found to fit the Rasch model, X (2)(df) = 16.953(14), p = 0.259 and 8.132(14), p = 0.882 for RA and SSc, respectively. Internal consistency of the Pol-ENAT was high (patient separation index = 0.85 and 0.89 for SSc and RA, respectively), and unidimensionality was confirmed. Cross-cultural differential item functioning (DIF) was detected in some subscales, and DIF-adjusted conversion tables were calibrated to enable cross-cultural comparison of data between Poland and the UK. Using a standard process in cross-cultural adaptation, conceptual equivalence was achieved between the original (UK) ENAT and the adapted Pol-ENAT. Fit to the Rasch model, confirmed that the construct validity, unidimensionality and internal consistency of the ENAT have been preserved.

Repression of class I transcription by cadmium is mediated by the protein phosphatase 2A

PubMed Central

Zhou, Lei; Le Roux, Gwenaëlle; Ducrot, Cécile; Chédin, Stéphane; Labarre, Jean; Riva, Michel; Carles, Christophe

2013-01-01

Toxic metals are part of our environment, and undue exposure to them leads to a variety of pathologies. In response, most organisms adapt their metabolism and have evolved systems to limit this toxicity and to acquire tolerance. Ribosome biosynthesis being central for protein synthesis, we analyzed in yeast the effects of a moderate concentration of cadmium (Cd2+) on Pol I transcription that represents >60% of the transcriptional activity of the cells. We show that Cd2+ rapidly and drastically shuts down the expression of the 35S rRNA. Repression does not result from a poisoning of any of the components of the class I transcriptional machinery by Cd2+, but rather involves a protein phosphatase 2A (PP2A)-dependent cellular signaling pathway that targets the formation/dissociation of the Pol I–Rrn3 complex. We also show that Pol I transcription is repressed by other toxic metals, such as Ag+ and Hg2+, which likewise perturb the Pol I–Rrn3 complex, but through PP2A-independent mechanisms. Taken together, our results point to a central role for the Pol I–Rrn3 complex as molecular switch for regulating Pol I transcription in response to toxic metals. PMID:23640330

A novel variant of DNA polymerase ζ, Rev3ΔC, highlights differential regulation of Pol32 as a subunit of polymerase δ versus ζ in Saccharomyces cerevisiae

PubMed Central

Siebler, Hollie M.; Lada, Artem G.; Baranovskiy, Andrey G.; Tahirov, Tahir H.; Pavlov, Youri I.

2014-01-01

Unrepaired DNA lesions often stall replicative DNA polymerases and are bypassed by translesion synthesis (TLS) to prevent replication fork collapse. Mechanisms of TLS are lesion- and species-specific, with a prominent role of specialized DNA polymerases with relaxed active sites. After nucleotide(s) are incorporated across from the altered base(s), the aberrant primer termini are typically extended by DNA polymerase ζ (pol ζ). As a result, pol ζ is responsible for most DNA damage-induced mutations. The mechanisms of sequential DNA polymerase switches in vivo remain unclear. The major replicative DNA polymerase δ (pol δ) shares two accessory subunits, called Pol31/Pol32 in yeast, with pol ζ. Inclusion of Pol31/Pol32 in the pol δ/pol ζ holoenzymes requires a [4Fe–4S] cluster in C-termini of the catalytic subunits. Disruption of this cluster in Pol ζ or deletion of POL32 attenuates induced mutagenesis. Here we describe a novel mutation affecting the catalytic subunit of pol ζ, rev3ΔC, which provides insight into the regulation of pol switches. Strains with Rev3ΔC, lacking the entire C-terminal domain and therefore the platform for Pol31/Pol32 binding, are partially proficient in Pol32-dependent UV-induced mutagenesis. This suggests an additional role of Pol32 in TLS, beyond being a pol ζ subunit, related to pol δ. In search for members of this regulatory pathway, we examined the effects of Maintenance of Genome Stability 1 (Mgs1) protein on mutagenesis in the absence of Rev3–Pol31/Pol32 interaction. Mgs1 may compete with Pol32 for binding to PCNA. Mgs1 overproduction suppresses induced mutagenesis, but had no effect on UV-mutagenesis in the rev3ΔC strain, suggesting that Mgs1 exerts its inhibitory effect by acting specifically on Pol32 bound to pol ζ. The evidence for differential regulation of Pol32 in pol δ and pol ζ emphasizes the complexity of polymerase switches. PMID:24819597

Infinitesimal Bäcklund Transformation and Conservation Laws for Non-autonomous Systems

NASA Astrophysics Data System (ADS)

Mahato, G.; Chowdhury, A. Roy

We have observed that it is possible to extend the concept of the infinitesimal Bäcklund transformation of Steudel to the case of non-autonomous systems. We have discussed the situation with the cylindrical KdV as example. The interesting point to note is that though the B.T. for Ckdv does not possess the usual property of generating one soliton in a single operation, yet it generates an infinite number of symmetries, which corroborates with those obtained through the expansion of the resolvant of the linear operator associated with the equation.Translated AbstractInfinitesimale Bäcklund-Transformation und Erhaltungsgesetze nichtautonomer SystemeWir finden, daß es möglich ist, das Steudelsche Konzept der infinitesimalen Bäcklund-Transformation auf den Fall nichtautonomer Systeme zu übertragen. Als ein Beispiel wird die Situation bei einer zylindrischen KdV-Gleichung pehandelt. Der interessante Punkt ist dabei, daß die Bäcklund-Transformation - obwohl sie für die zylindrische KdV-Gleichung die übliche Eigenschaft, ein Soliton durch eine einzige Operation zu erzeugen, nicht besitzt - doch eine unendliche Zahl von Symmetrien erzeugt. Das bestätigt die Ergebnisse, die man durch Entwicklung der Resolvente des mit der Gleichung verknüpften linearen Operators erhält.

Statistische Physik

NASA Astrophysics Data System (ADS)

Fließbach, Torsten

In der Statistischen Physik befassen wir uns mit Systemen aus sehr vielen Teilchen. Beispiele hierfür sind die Atome eines Gases oder einer Flüssigkeit, die Phononen eines Festkörpers oder die Photonen in einem Plasma. Die Gesetze für die Bewegung einzelner Teilchen sind durch die Mechanik oder die Quantenmechanik gegeben. Aufgrund der großen Zahl der Teilchen (zum Beispiel N = 6 • 1023 für ein Mol eines Gases) sind die Bewegungsgleichungen jedoch nicht auswertbar. Das Ergebnis einer solchen Auswertung, also etwa die Bahnen von 6•1023 Teilchen, wäre auch uninteressant und irrelevant. Die Behandlung dieser Systeme erfolgt daher statistisch, das heißt auf der Grundlage von Annahmen über dieWahrscheinlichkeit verschiedener Bahnen oder Zustände.

TFIIIC bound DNA elements in nuclear organization and insulation.

PubMed

Kirkland, Jacob G; Raab, Jesse R; Kamakaka, Rohinton T

2013-01-01

tRNA genes (tDNAs) have been known to have barrier insulator function in budding yeast, Saccharomyces cerevisiae, for over a decade. tDNAs also play a role in genome organization by clustering at sites in the nucleus and both of these functions are dependent on the transcription factor TFIIIC. More recently TFIIIC bound sites devoid of pol III, termed Extra-TFIIIC sites (ETC) have been identified in budding yeast and these sites also function as insulators and affect genome organization. Subsequent studies in Schizosaccharomyces pombe showed that TFIIIC bound sites were insulators and also functioned as Chromosome Organization Clamps (COC); tethering the sites to the nuclear periphery. Very recently studies have moved to mammalian systems where pol III genes and their associated factors have been investigated in both mouse and human cells. Short interspersed nuclear elements (SINEs) that bind TFIIIC, function as insulator elements and tDNAs can also function as both enhancer - blocking and barrier insulators in these organisms. It was also recently shown that tDNAs cluster with other tDNAs and with ETCs but not with pol II transcribed genes. Intriguingly, TFIIIC is often found near pol II transcription start sites and it remains unclear what the consequences of TFIIIC based genomic organization are and what influence pol III factors have on pol II transcribed genes and vice versa. In this review we provide a comprehensive overview of the known data on pol III factors in insulation and genome organization and identify the many open questions that require further investigation. This article is part of a Special Issue entitled: Transcription by Odd Pols. Copyright © 2012 Elsevier B.V. All rights reserved.

Mechanism of asymmetric polymerase assembly at the eukaryotic replication fork

PubMed Central

Georgescu, Roxana E; Langston, Lance; Yao, Nina Y; Yurieva, Olga; Zhang, Dan; Finkelstein, Jeff; Agarwal, Tani; O’Donnell, Mike E

2015-01-01

Eukaryotes use distinct polymerases for leading- and lagging-strand replication, but how they target their respective strands is uncertain. We reconstituted Saccharomyces cerevisiae replication forks and found that CMG helicase selects polymerase (Pol) ε to the exclusion of Pol δ on the leading strand. Even if Pol δ assembles on the leading strand, Pol ε rapidly replaces it. Pol δ–PCNA is distributive with CMG, in contrast to its high stability on primed ssDNA. Hence CMG will not stabilize Pol δ, instead leaving the leading strand accessible for Pol ε and stabilizing Pol ε. Comparison of Pol ε and Pol δ on a lagging-strand model DNA reveals the opposite. Pol δ dominates over excess Pol ε on PCNA-primed ssDNA. Thus, PCNA strongly favors Pol δ over Pol ε on the lagging strand, but CMG over-rides and flips this balance in favor of Pol ε on the leading strand. PMID:24997598

ELAV Links Paused Pol II to Alternative Polyadenylation in the Drosophila Nervous System

PubMed Central

Oktaba, Katarzyna; Zhang, Wei; Lotz, Thea Sabrina; Jun, David Jayhyun; Lemke, Sandra Beatrice; Ng, Samuel Pak; Esposito, Emilia; Levine, Michael; Hilgers, Valérie

2014-01-01

SUMMARY Alternative polyadenylation (APA) has been implicated in a variety of developmental and disease processes. A particularly dramatic form of APA occurs in the developing nervous system of flies and mammals, whereby various developmental genes undergo coordinate 3′ UTR extension. In Drosophila, the RNA-binding protein ELAV inhibits RNA processing at proximal polyadenylation sites, thereby fostering the formation of exceptionally long 3′ UTRs. Here, we present evidence that paused Pol II promotes recruitment of ELAV to extended genes. Replacing promoters of extended genes with heterologous promoters blocks normal 3′ extension in the nervous system, while extension-associated promoters can induce 3′ extension in ectopic tissues expressing ELAV. Computational analyses suggest that promoter regions of extended genes tend to contain paused Pol II and associated cis-regulatory elements such as GAGA. ChIP-Seq assays identify ELAV in the promoter regions of extended genes. Our study provides evidence for a regulatory link between promoter-proximal pausing and APA. PMID:25544561

Identifikationsverfahren zur Analyse von EEG-Signalen bei Epilepsie mit Reaktions-Diffusions Netzwerken

NASA Astrophysics Data System (ADS)

Gollas, F.; Tetzlaff, R.

2007-06-01

Partielle Differentialgleichungen des Reaktions-Diffusions-Typs beschreiben Phänomene wie Musterbildung, nichtlineare Wellenausbreitung und deterministisches Chaos und werden oft zur Untersuchung komplexer Vorgänge auf den Gebieten der Biologie, Chemie und Physik herangezogen. Zellulare Nichtlineare Netzwerke (CNN) sind eine räumliche Anordnung vergleichsweise einfacher dynamischer Systeme, die eine lokale Kopplung untereinander aufweisen. Durch eine Diskretisierung der Ortsvariablen können Reaktions-Diffusions-Gleichungen häufig auf CNN mit nichtlinearen Gewichtsfunktionen abgebildet werden. Die resultierenden Reaktions-Diffusions-CNN (RD-CNN) weisen dann in ihrer Dynamik näherungsweise gleiches Verhalten wie die zugrunde gelegten Reaktions-Diffusions-Systeme auf. Werden RD-CNN zur Identifikation neuronaler Strukturen anhand von EEG-Signalen herangezogen, so besteht die Möglichkeit festzustellen, ob das gefundene Netzwerk lokale Aktivität aufweist. Die von Chua eingeführte Theorie der lokalen Aktivität Chua (1998); Dogaru und Chua (1998) liefert eine notwendige Bedingung für das Auftreten von emergentem Verhalten in zellularen Netzwerken. Änderungen in den Parametern bestimmter RD-CNN könnten auf bevorstehende epileptische Anfälle hinweisen. In diesem Beitrag steht die Identifikation neuronaler Strukturen anhand von EEG-Signalen durch Reaktions-Diffusions-Netzwerke im Vordergrund der dargestellten Untersuchungen. In der Ergebnisdiskussion wird insbesondere auch die Frage nach einer geeigneten Netzwerkstruktur mit minimaler Komplexität behandelt.

Test Protocols for Advanced Inverter Interoperability Functions – Main Document

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

Johnson, Jay Dean; Gonzalez, Sigifredo; Ralph, Mark E.

2013-11-01

Distributed energy resources (DER) such as photovoltaic (PV) systems, when deployed in a large scale, are capable of influencing significantly the operation of power systems. Looking to the future, stakeholders are working on standards to make it possible to manage the potentially complex interactions between DER and the power system. In 2009, the Electric Power Research Institute (EPRI), Sandia National Laboratories (SNL) with the U.S. Department of Energy (DOE), and the Solar Electric Power Association (SEPA) initiated a large industry collaborative to identify and standardize definitions for a set of DER grid support functions. While the initial effort concentrated onmore » grid-tied PV inverters and energy storage systems, the concepts have applicability to all DER. A partial product of this on-going effort is a reference definitions document (IEC TR 61850-90-7, Object models for power converters in distributed energy resources (DER) systems) that has become a basis for expansion of related International Electrotechnical Commission (IEC) standards, and is supported by US National Institute of Standards and Technology (NIST) Smart Grid Interoperability Panel (SGIP). Some industry-led organizations advancing communications protocols have also embraced this work. As standards continue to evolve, it is necessary to develop test protocols to independently verify that the inverters are properly executing the advanced functions. Interoperability is assured by establishing common definitions for the functions and a method to test compliance with operational requirements. This document describes test protocols developed by SNL to evaluate the electrical performance and operational capabilities of PV inverters and energy storage, as described in IEC TR 61850-90-7. While many of these functions are not currently required by existing grid codes or may not be widely available commercially, the industry is rapidly moving in that direction. Interoperability issues are already apparent as some of these inverter capabilities are being incorporated in large demonstration and commercial projects. The test protocols are intended to be used to verify acceptable performance of inverters within the standard framework described in IEC TR 61850-90-7. These test protocols, as they are refined and validated over time, can become precursors for future certification test procedures for DER advanced grid support functions.« less

Test Protocols for Advanced Inverter Interoperability Functions - Appendices

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

Johnson, Jay Dean; Gonzalez, Sigifredo; Ralph, Mark E.

2013-11-01

Distributed energy resources (DER) such as photovoltaic (PV) systems, when deployed in a large scale, are capable of influencing significantly the operation of power systems. Looking to the future, stakeholders are working on standards to make it possible to manage the potentially complex interactions between DER and the power system. In 2009, the Electric Power Research Institute (EPRI), Sandia National Laboratories (SNL) with the U.S. Department of Energy (DOE), and the Solar Electric Power Association (SEPA) initiated a large industry collaborative to identify and standardize definitions for a set of DER grid support functions. While the initial effort concentrated onmore » grid-tied PV inverters and energy storage systems, the concepts have applicability to all DER. A partial product of this on-going effort is a reference definitions document (IEC TR 61850-90-7, Object models for power converters in distributed energy resources (DER) systems) that has become a basis for expansion of related International Electrotechnical Commission (IEC) standards, and is supported by US National Institute of Standards and Technology (NIST) Smart Grid Interoperability Panel (SGIP). Some industry-led organizations advancing communications protocols have also embraced this work. As standards continue to evolve, it is necessary to develop test protocols to independently verify that the inverters are properly executing the advanced functions. Interoperability is assured by establishing common definitions for the functions and a method to test compliance with operational requirements. This document describes test protocols developed by SNL to evaluate the electrical performance and operational capabilities of PV inverters and energy storage, as described in IEC TR 61850-90-7. While many of these functions are not now required by existing grid codes or may not be widely available commercially, the industry is rapidly moving in that direction. Interoperability issues are already apparent as some of these inverter capabilities are being incorporated in large demonstration and commercial projects. The test protocols are intended to be used to verify acceptable performance of inverters within the standard framework described in IEC TR 61850-90-7. These test protocols, as they are refined and validated over time, can become precursors for future certification test procedures for DER advanced grid support functions.« less

A Conserved Nuclear Cyclophilin Is Required for Both RNA Polymerase II Elongation and Co-transcriptional Splicing in Caenorhabditis elegans

PubMed Central

Ahn, Jeong H.; Rechsteiner, Andreas; Strome, Susan; Kelly, William G.

2016-01-01

The elongation phase of transcription by RNA Polymerase II (Pol II) involves numerous events that are tightly coordinated, including RNA processing, histone modification, and chromatin remodeling. RNA splicing factors are associated with elongating Pol II, and the interdependent coupling of splicing and elongation has been documented in several systems. Here we identify a conserved, multi-domain cyclophilin family member, SIG-7, as an essential factor for both normal transcription elongation and co-transcriptional splicing. In embryos depleted for SIG-7, RNA levels for over a thousand zygotically expressed genes are substantially reduced, Pol II becomes significantly reduced at the 3’ end of genes, marks of transcription elongation are reduced, and unspliced mRNAs accumulate. Our findings suggest that SIG-7 plays a central role in both Pol II elongation and co-transcriptional splicing and may provide an important link for their coordination and regulation. PMID:27541139

PubMed

Wildner, Manfred

2018-06-01

„Ich habe doch nur mit dem Finger gedroht“, sagte der Angeklagte, und unterließ es unfairerweise darauf hinzuweisen, dass dieser am Abzug einer Pistole gelegen hatte. Der Bezug dieses Bonmots zum Gesundheitswesen soll im Folgenden weniger auf die konkreten gesundheitlichen Risiken durch Schusswaffen gelegt werden, sondern vielmehr auf die nicht weniger bedeutsame Rolle des Kontextes für Gesundheit, Krankheit und Wohlbefinden. Dass der „Kontext“, verstanden als System- und Sinnzusammenhang, sowohl das objektive Auftreten von Krankheiten in ihrer Häufigkeit und Schwere als auch das subjektive Erleben von Gesundheitszuständen beeinflusst, ist hinreichend bekannt.

A high-pressure van der Waals compound in solid nitrogen-helium mixtures

NASA Technical Reports Server (NTRS)

Vos, W. L.; Finger, L. W.; Hemley, R. J.; Hu, J. Z.; Mao, H. K.; Schouten, J. A.

1992-01-01

A detailed diamond anvil-cell study using synchrotron X-ray diffraction, Raman scattering, and optical microscopy has been conducted for the He-N system, with a view to the weakly-bound van der Waals molecule interactions that can be formed in the gas phase. High pressure is found to stabilize the formation of a stoichiometric, solid van der Waals compound of He(N2)11 composition which may exemplify a novel class of compounds found at high pressures in the interiors of the outer planets and their satellites.

Study of a Secondary Power System Based on an Intermediate Bus Converter and POLs

NASA Astrophysics Data System (ADS)

Santoja, Almudena; Fernandez, Arturo; Tonicello, Ferdinando

2014-08-01

Secondary power systems in satellites are everything but standard nowadays. All sorts of options can be found and, in the end, a new custom design is used in most of the cases. Even though this might be interesting in some specific cases, for most of them it would be more convenient to have a straightforward system based on standard components. One of the options to achieve this is to design the secondary power system with an Intermediate Bus Converter (IBC) and Point of Load converters (POLs). This paper presents a study of this architecture and some experimental verifications to establish some basic rules devoted to achieve an optimum design of this system.

Subunit Compositions of the RNA-Silencing Enzymes Pol IV and Pol V Reveal Their Origins as Specialized Forms of RNA Polymerase II

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

Ream, Thomas S.; Haag, J. R.; Wierzbicki, A. T.

2009-01-30

In addition to RNA polymerases I, II, and III, the essential RNA polymerases present in all eukaryotes, plants have two additional nuclear RNA polymerases, abbreviated as Pol IV and Pol V, that play nonredundant roles in siRNA-directed DNA methylation and gene silencing. We show that Arabidopsis Pol IV and Pol V are composed of subunits that are paralogous or identical to the 12 subunits of Pol II. Four subunits of Pol IV are distinct from their Pol II paralogs, six subunits of Pol V are distinct from their Pol II paralogs, and four subunits differ between Pol IV and Polmore » V. Importantly, the subunit differences occur in key positions relative to the template entry and RNA exit paths. Our findings support the hypothesis that Pol IV and Pol V are Pol II-like enzymes that evolved specialized roles in the production of noncoding transcripts for RNA silencing and genome defense.« less

Repriming by PrimPol is critical for DNA replication restart downstream of lesions and chain-terminating nucleosides.

PubMed

Kobayashi, Kaori; Guilliam, Thomas A; Tsuda, Masataka; Yamamoto, Junpei; Bailey, Laura J; Iwai, Shigenori; Takeda, Shunichi; Doherty, Aidan J; Hirota, Kouji

2016-08-02

PrimPol is a DNA damage tolerance enzyme possessing both translesion synthesis (TLS) and primase activities. To uncover its potential role in TLS-mediated IgVλ hypermutation and define its interplay with other TLS polymerases, PrimPol(-/-) and PrimPol(-/-)/Polη(-/-)/Polζ (-/-) gene knockouts were generated in avian cells. Loss of PrimPol had no significant impact on the rate of hypermutation or the mutation spectrum of IgVλ. However, PrimPol(-/-) cells were sensitive to methylmethane sulfonate, suggesting that it may bypass abasic sites at the IgVλ segment by repriming DNA synthesis downstream of these sites. PrimPol(-/-) cells were also sensitive to cisplatin and hydroxyurea, indicating that it assists in maintaining / restarting replication at a variety of lesions. To accurately measure the relative contribution of the TLS and primase activities, we examined DNA damage sensitivity in PrimPol(-/-) cells complemented with polymerase or primase-deficient PrimPol. Polymerase-defective, but not primase-deficient, PrimPol suppresses the hypersensitivity of PrimPol(-/-) cells. This indicates that its primase, rather than TLS activity, is pivotal for DNA damage tolerance. Loss of TLS polymerases, Polη and Polζ has an additive effect on the sensitivity of PrimPol(-/-) cells. Moreover, we found that PrimPol and Polη-Polζ redundantly prevented cell death and facilitated unperturbed cell cycle progression. PrimPol(-/-) cells also exhibited increased sensitivity to a wide variety of chain-terminating nucleoside analogs (CTNAs). PrimPol could perform close-coupled repriming downstream of CTNAs and oxidative damage in vitro. Together, these results indicate that PrimPol's repriming activity plays a central role in reinitiating replication downstream from CTNAs and other specific DNA lesions.

RNA polymerases IV and V influence the 3' boundaries of Polymerase II transcription units in Arabidopsis.

PubMed

McKinlay, Anastasia; Podicheti, Ram; Wendte, Jered M; Cocklin, Ross; Rusch, Douglas B

2018-02-01

Nuclear multisubunit RNA polymerases IV and V (Pol IV and Pol V) evolved in plants as specialized forms of Pol II. Their functions are best understood in the context of RNA-directed DNA methylation (RdDM), a process in which Pol IV-dependent 24 nt siRNAs direct the de novo cytosine methylation of regions transcribed by Pol V. Pol V has additional functions, independent of Pol IV and 24 nt siRNA biogenesis, in maintaining the repression of transposons and genomic repeats whose silencing depends on maintenance cytosine methylation. Here we report that Pol IV and Pol V play unexpected roles in defining the 3' boundaries of Pol II transcription units. Nuclear run-on assays reveal that in the absence of Pol IV or Pol V, Pol II occupancy downstream of poly A sites increases for approximately 12% of protein-coding genes. This effect is most pronounced for convergently transcribed gene pairs. Although Pols IV and V are detected near transcript ends of the affected Pol II - transcribed genes, their role in limiting Pol II read-through is independent of siRNA biogenesis or cytosine methylation for the majority of these genes. Interestingly, we observed that splicing was less efficient in pol IV or pol V mutant plants, compared to wild-type plants, suggesting that Pol IV or Pol V might affect pre-mRNA processing. We speculate that Pols IV and V (and/or their associated factors) play roles in Pol II transcription termination and pre-mRNA splicing by influencing polymerase elongation rates and/or release at collision sites for convergent genes.

System-of-Systems Approach for Integrated Energy Systems Modeling and Simulation: Preprint

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

Mittal, Saurabh; Ruth, Mark; Pratt, Annabelle

Today’s electricity grid is the most complex system ever built—and the future grid is likely to be even more complex because it will incorporate distributed energy resources (DERs) such as wind, solar, and various other sources of generation and energy storage. The complexity is further augmented by the possible evolution to new retail market structures that provide incentives to owners of DERs to support the grid. To understand and test new retail market structures and technologies such as DERs, demand-response equipment, and energy management systems while providing reliable electricity to all customers, an Integrated Energy System Model (IESM) is beingmore » developed at NREL. The IESM is composed of a power flow simulator (GridLAB-D), home energy management systems implemented using GAMS/Pyomo, a market layer, and hardware-in-the-loop simulation (testing appliances such as HVAC, dishwasher, etc.). The IESM is a system-of-systems (SoS) simulator wherein the constituent systems are brought together in a virtual testbed. We will describe an SoS approach for developing a distributed simulation environment. We will elaborate on the methodology and the control mechanisms used in the co-simulation illustrated by a case study.« less

Control Strategies for Distributed Energy Resources to Maximize the Use of Wind Power in Rural Microgrids

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

Lu, Shuai; Elizondo, Marcelo A.; Samaan, Nader A.

2011-10-10

The focus of this paper is to design control strategies for distributed energy resources (DERs) to maximize the use of wind power in a rural microgrid. In such a system, it may be economical to harness wind power to reduce the consumption of fossil fuels for electricity production. In this work, we develop control strategies for DERs, including diesel generators, energy storage and demand response, to achieve high penetration of wind energy in a rural microgrid. Combinations of centralized (direct control) and decentralized (autonomous response) control strategies are investigated. Detailed dynamic models for a rural microgrid are built to conductmore » simulations. The system response to large disturbances and frequency regulation are tested. It is shown that optimal control coordination of DERs can be achieved to maintain system frequency while maximizing wind power usage and reducing the wear and tear on fossil fueled generators.« less

Status and Needs of Power Electronics for Photovoltaic Inverters

NASA Astrophysics Data System (ADS)

Qin, Y. C.; Mohan, N.; West, R.; Bonn, R.

2002-06-01

Photovoltaics is the utility connected distributed energy resource (DER) that is in widespread use today. It has one element, the inverter, which is common with all DER sources except rotating generators. The inverter is required to transfer dc energy to ac energy. With all the DER technologies, (solar, wind, fuel cells, and microturbines) the inverter is still an immature product that will result in reliability problems in fielded systems. Today, the PV inverter is a costly and complex component of PV systems that produce ac power. Inverter MTFF (mean time to first failure) is currently unacceptable. Low inverter reliability contributes to unreliable fielded systems and a loss of confidence in renewable technology. The low volume of PV inverters produced restricts the manufacturing to small suppliers without sophisticated research and reliability programs or manufacturing methods. Thus, the present approach to PV inverter supply has low probability of meeting DOE reliability goals.

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

Mendes, Goncalo; Feng, Wei; Stadler, Michael

The following paper conducts a regional analysis of the U.S. and Chinese buildings? potential for adopting Distributed Energy Resources (DER). The expected economics of DER in 2020-2025 is modeled for a commercial and a multi-family residential building in different climate zones. The optimal building energy economic performance is calculated using the Distributed Energy Resources Customer Adoption Model (DER CAM) which minimizes building energy costs for a typical reference year of operation. Several DER such as combined heat and power (CHP) units, photovoltaics, and battery storage are considered. The results indicate DER have economic and environmental competitiveness potential, especially for commercialmore » buildings in hot and cold climates of both countries. In the U.S., the average expected energy cost savings in commercial buildings from DER CAM?s suggested investments is 17percent, while in Chinese buildings is 12percent. The electricity tariffs structure and prices along with the cost of natural gas, represent important factors in determining adoption of DER, more so than climate. High energy pricing spark spreads lead to increased economic attractiveness of DER. The average emissions reduction in commercial buildings is 19percent in the U.S. as a result of significant investments in PV, whereas in China, it is 20percent and driven by investments in CHP. Keywords: Building Modeling and Simulation, Distributed Energy Resources (DER), Energy Efficiency, Combined Heat and Power (CHP), CO2 emissions 1. Introduction The transition from a centralized and fossil-based energy paradigm towards the decentralization of energy supply and distribution has been a major subject of research over the past two decades. Various concerns have brought the traditional model into question; namely its environmental footprint, its structural inflexibility and inefficiency, and more recently, its inability to maintain acceptable reliability of supply. Under such a troubled setting, distributed energy resources (DER) comprising of small, modular, electrical renewable or fossil-based electricity generation units placed at or near the point of energy consumption, has gained much attention as a viable alternative or addition to the current energy system. In 2010, China consumed about 30percent of its primary energy in the buildings sector, leading the country to pay great attention to DER development and its applications in buildings. During the 11th Five Year Plan (FYP), China has implemented 371 renewable energy building demonstration projects, and 210 photovoltaics (PV) building integration projects. At the end of the 12th FYP, China is targeting renewable energy to provide 10percent of total building energy, and to save 30 metric tons of CO2 equivalents (mtce) of energy with building integrated renewables. China is also planning to implement one thousand natural gas-based distributed cogeneration demonstration projects with energy utilization rates over 70percent in the 12th FYP. All these policy targets require significant DER systems development for building applications. China?s fast urbanization makes building energy efficiency a crucial economic issue; however, only limited studies have been done that examine how to design and select suitable building energy technologies in its different regions. In the U.S., buildings consumed 40percent of the total primary energy in 2010 [1] and it is estimated that about 14 billion m2 of floor space of the existing building stock will be remodeled over the next 30 years. Most building?s renovation work has been on building envelope, lighting and HVAC systems. Although interest has emerged, less attention is being paid to DER for buildings. This context has created opportunities for research, development and progressive deployment of DER, due to its potential to combine the production of power and heat (CHP) near the point of consumption and delivering multiple benefits to customers, such as cost« less

Binding and Diffusion of Lithium in Graphite: Quantum Monte Carlo Benchmarks and Validation of van der Waals Density Functional Methods

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

Ganesh, P.; Kim, Jeongnim; Park, Changwon

2014-11-03

In highly accurate diffusion quantum Monte Carlo (QMC) studies of the adsorption and diffusion of atomic lithium in AA-stacked graphite are compared with van der Waals-including density functional theory (DFT) calculations. Predicted QMC lattice constants for pure AA graphite agree with experiment. Pure AA-stacked graphite is shown to challenge many van der Waals methods even when they are accurate for conventional AB graphite. Moreover, the highest overall DFT accuracy, considering pure AA-stacked graphite as well as lithium binding and diffusion, is obtained by the self-consistent van der Waals functional vdW-DF2, although errors in binding energies remain. Empirical approaches based onmore » point charges such as DFT-D are inaccurate unless the local charge transfer is assessed. Our results demonstrate that the lithium carbon system requires a simultaneous highly accurate description of both charge transfer and van der Waals interactions, favoring self-consistent approaches.« less

Interaction between the Rev1 C-terminal Domain and the PolD3 Subunit of Polζ Suggests a Mechanism of Polymerase Exchange upon Rev1/Polζ-Dependent Translesion Synthesis

PubMed Central

Pustovalova, Yulia; Magalhães, Mariana T. Q.; D’Souza, Sanjay; Rizzo, Alessandro A.; Korza, George; Walker, Graham C.; Korzhnev, Dmitry M.

2016-01-01

Translesion synthesis (TLS) is a mutagenic branch of cellular DNA damage tolerance that enables bypass replication over DNA lesions carried out by specialized low-fidelity DNA polymerases. The replicative bypass of most types of DNA damage is performed in a two-step process of Rev1/Polζ-dependent TLS. In the first step, a Y-family TLS enzyme, typically Polη, Polι or Polκ, inserts a nucleotide across DNA lesion. In the second step, a four-subunit B-family DNA polymerase Polζ (Rev3/Rev7/PolD2/PolD3 complex) extends the distorted DNA primer-template. The coordinated action of error-prone TLS enzymes is regulated through their interactions with the two scaffold proteins, the sliding clamp PCNA and the TLS polymerase Rev1. Rev1 interactions with all other TLS enzymes are mediated by its C-terminal domain (Rev1-CT), which can simultaneously bind the Rev7 subunit of Polζ and Rev1-interacting regions (RIRs) from Polη, Polι or Polκ. In this work, we identified a previously unknown RIR motif in the C-terminal part of PolD3 subunit of Polζ whose interaction with the Rev1-CT is among the tightest mediated by RIR motifs. Three-dimensional structure of the Rev1-CT/PolD3-RIR complex determined by NMR spectroscopy revealed a structural basis for the relatively high affinity of this interaction. The unexpected discovery of PolD3-RIR motif suggests a mechanism of 'inserter' to 'extender' DNA polymerase switch upon Rev1/Polζ-dependent TLS, in which the PolD3-RIR binding to the Rev1-CT (i) helps displace the 'inserter' Polη, Polι or Polκ from its complex with Rev1, and (ii) facilitates assembly of the four-subunit 'extender' Polζ through simultaneous interaction of Rev1-CT with Rev7 and PolD3 subunits. PMID:26982350

Construction of a Der p2-transgenic plant for the alleviation of airway inflammation

PubMed Central

Lee, CC; Ho, H; Lee, KT; Jeng, ST; Chiang, BL

2011-01-01

In clinical therapy, the amount of antigen administered to achieve oral tolerance for allergic diseases is large, and the cost is a major consideration. In this study, we used tobacco plants to develop a large-scale protein production system for allergen-specific immunotherapy, and we investigated the mechanisms of oral tolerance induced by a transgenic plant-derived antigen. We used plants (tobacco leaves) transgenic for the Dermatophagoides pteronyssinus 2 (Der p2) antigen to produce Der p2. Mice received total protein extract from Der p2 orally once per day over 6 days (days 0–2 and days 6–8). Mice were also sensitized and challenged with yeast-derived recombinant Der p2 (rDer p2), after which the mice were examined for airway hyper-responsiveness and airway inflammation. After sensitization and challenge with rDer p2, mice that were fed with total protein extracted from transgenic plants showed decreases in serum Der p2-specific IgE and IgG1 titers, decreased IL-5 and eotaxin levels in bronchial alveolar lavage fluid, and eosinophil infiltration in the airway. In addition, hyper-responsiveness was also decreased in mice that were fed with total protein extracted from transgenic plants, and CD4+CD25+Foxp3+ regulatory T cells were significantly increased in mediastinal and mesenteric lymph nodes. Furthermore, splenocytes isolated from transgenic plant protein-fed mice exhibited decreased proliferation and increased IL-10 secretion after stimulation with rDer p2. The data here suggest that allergen-expressing transgenic plants could be used for therapeutic purposes for allergic diseases. PMID:21602845

van der Waals Interactions on the Mesoscale: Open-Science Implementation, Anisotropy, Retardation, and Solvent Effects.

PubMed

Dryden, Daniel M; Hopkins, Jaime C; Denoyer, Lin K; Poudel, Lokendra; Steinmetz, Nicole F; Ching, Wai-Yim; Podgornik, Rudolf; Parsegian, Adrian; French, Roger H

2015-09-22

The self-assembly of heterogeneous mesoscale systems is mediated by long-range interactions, including van der Waals forces. Diverse mesoscale architectures, built of optically and morphologically anisotropic elements such as DNA, collagen, single-walled carbon nanotubes, and inorganic materials, require a tool to calculate the forces, torques, interaction energies, and Hamaker coefficients that govern assembly in such systems. The mesoscale Lifshitz theory of van der Waals interactions can accurately describe solvent and temperature effects, retardation, and optically and morphologically anisotropic materials for cylindrical and planar interaction geometries. The Gecko Hamaker open-science software implementation of this theory enables new and sophisticated insights into the properties of important organic/inorganic systems: interactions show an extended range of magnitudes and retardation rates, DNA interactions show an imprint of base pair composition, certain SWCNT interactions display retardation-dependent nonmonotonicity, and interactions are mapped across a range of material systems in order to facilitate rational mesoscale design.

TFIIIC Bound DNA Elements in Nuclear Organization and Insulation

PubMed Central

Kirkland, Jacob G.; Raab, Jesse R.

2012-01-01

tRNA genes (tDNAs) have been known to have barrier insulator function in budding yeast, Saccharomyces cerevisiae, for over a decade. tDNAs also play a role in genome organization by clustering at sites in the nucleus and both of these functions are dependent on the transcription factor TFIIIC. More recently TFIIIC bound sites devoid of pol III, termed Extra-TFIIIC sites (ETC) have been identified in budding yeast and these sites also function as insulators and affect genome organization. Subsequent studies in Schizosaccharomyces pombe showed that TFIIIC bound sites were insulators and also functioned as Chromosome Organization Clamps (COC); tethering the sites to the nuclear periphery. Very recently studies have moved to mammalian systems where pol III genes and their associated factors have been investigated in both mouse and human cells. Short Interspersed Nuclear Elements (SINEs) that bind TFIIIC, function as insulator elements and tDNAs can also function as both enhancer -blocking and barrier insulators in these organisms. It was also recently shown that tDNAs cluster with other tDNAs and with ETCs but not with pol II transcribed genes. Intriguingly, TFIIIC is often found near pol II transcription start sites and it remains unclear what the consequences of TFIIIC based genomic organization are and what influence pol III factors have on pol II transcribed genes and vise versa. In this review we provide a comprehensive overview of the known data on pol III factors in insulation and genome organization and identify the many open questions that require further investigation. \\ PMID:23000638

Comparative transcript profiling of the fertile and sterile flower buds of pol CMS in B. napus.

PubMed

An, Hong; Yang, Zonghui; Yi, Bin; Wen, Jing; Shen, Jinxiong; Tu, Jinxing; Ma, Chaozhi; Fu, Tingdong

2014-04-03

The Polima (pol) system of cytoplasmic male sterility (CMS) and its fertility restoration gene Rfp have been used in hybrid breeding in Brassica napus, which has greatly improved the yield of rapeseed. However, the mechanism of the male sterility transition in pol CMS remains to be determined. To investigate the transcriptome during the male sterility transition in pol CMS, a near-isogenic line (NIL) of pol CMS was constructed. The phenotypic features and sterility stage were confirmed by anatomical analysis. Subsequently, we compared the genomic expression profiles of fertile and sterile young flower buds by RNA-Seq. A total of 105,481,136 sequences were successfully obtained. These reads were assembled into 112,770 unigenes, which composed the transcriptome of the bud. Among these unigenes, 72,408 (64.21%) were annotated using public protein databases and classified into functional clusters. In addition, we investigated the changes in expression of the fertile and sterile buds; the RNA-seq data showed 1,148 unigenes had significantly different expression and they were mainly distributed in metabolic and protein synthesis pathways. Additionally, some unigenes controlling anther development were dramatically down-regulated in sterile buds. These results suggested that an energy deficiency caused by orf224/atp6 may inhibit a series of genes that regulate pollen development through nuclear-mitochondrial interaction. This results in the sterility of pol CMS by leading to the failure of sporogenous cell differentiation. This study may provide assistance for detailed molecular analysis and a better understanding of pol CMS in B. napus.

Bacillus subtilis DNA polymerases, PolC and DnaE, are required for both leading and lagging strand synthesis in SPP1 origin-dependent DNA replication

PubMed Central

Seco, Elena M.

2017-01-01

Abstract Firmicutes have two distinct replicative DNA polymerases, the PolC leading strand polymerase, and PolC and DnaE synthesizing the lagging strand. We have reconstituted in vitro Bacillus subtilis bacteriophage SPP1 θ-type DNA replication, which initiates unidirectionally at oriL. With this system we show that DnaE is not only restricted to lagging strand synthesis as previously suggested. DnaG primase and DnaE polymerase are required for initiation of DNA replication on both strands. DnaE and DnaG synthesize in concert a hybrid RNA/DNA ‘initiation primer’ on both leading and lagging strands at the SPP1 oriL region, as it does the eukaryotic Pol α complex. DnaE, as a RNA-primed DNA polymerase, extends this initial primer in a reaction modulated by DnaG and one single-strand binding protein (SSB, SsbA or G36P), and hands off the initiation primer to PolC, a DNA-primed DNA polymerase. Then, PolC, stimulated by DnaG and the SSBs, performs the bulk of DNA chain elongation at both leading and lagging strands. Overall, these modulations by the SSBs and DnaG may contribute to the mechanism of polymerase switch at Firmicutes replisomes. PMID:28575448

van der Waals forces in density functional theory: a review of the vdW-DF method.

PubMed

Berland, Kristian; Cooper, Valentino R; Lee, Kyuho; Schröder, Elsebeth; Thonhauser, T; Hyldgaard, Per; Lundqvist, Bengt I

2015-06-01

A density functional theory (DFT) that accounts for van der Waals (vdW) interactions in condensed matter, materials physics, chemistry, and biology is reviewed. The insights that led to the construction of the Rutgers-Chalmers van der Waals density functional (vdW-DF) are presented with the aim of giving a historical perspective, while also emphasizing more recent efforts which have sought to improve its accuracy. In addition to technical details, we discuss a range of recent applications that illustrate the necessity of including dispersion interactions in DFT. This review highlights the value of the vdW-DF method as a general-purpose method, not only for dispersion bound systems, but also in densely packed systems where these types of interactions are traditionally thought to be negligible.

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

Tang, Yingying; Homer, Juliet S.; McDermott, Thomas E.

The purpose of this document is to summarize types of electric distribution system analyses along with their application and relative maturity. Particular emphasis is placed on analyses associated with distributed energy resources (DERs). Analyses are separated into the categories of power flow, power quality, fault analysis, dynamic analysis and market analysis. Studies associated with DERs are called out in a separate section.

Brain-derived neurotrophic factor as a regulator of systemic and brain energy metabolism and cardiovascular health

PubMed Central

Rothman, Sarah M; Griffioen, Kathleen J; Wan, Ruiqian; Mattson, Mark P

2012-01-01

Overweight sedentary individuals are at increased risk for cardiovascular disease, diabetes, and some neurological disorders. Beneficial effects of dietary energy restriction (DER) and exercise on brain structural plasticity and behaviors have been demonstrated in animal models of aging and acute (stroke and trauma) and chronic (Alzheimer's and Parkinson's diseases) neurological disorders. The findings described later, and evolutionary considerations, suggest brain-derived neurotrophic factor (BDNF) plays a critical role in the integration and optimization of behavioral and metabolic responses to environments with limited energy resources and intense competition. In particular, BDNF signaling mediates adaptive responses of the central, autonomic, and peripheral nervous systems from exercise and DER. In the hypothalamus, BDNF inhibits food intake and increases energy expenditure. By promoting synaptic plasticity and neurogenesis in the hippocampus, BDNF mediates exercise- and DER-induced improvements in cognitive function and neuroprotection. DER improves cardiovascular stress adaptation by a mechanism involving enhancement of brainstem cholinergic activity. Collectively, findings reviewed in this paper provide a rationale for targeting BDNF signaling for novel therapeutic interventions in a range of metabolic and neurological disorders. PMID:22548651

Design, modeling, simulation and evaluation of a distributed energy system

NASA Astrophysics Data System (ADS)

Cultura, Ambrosio B., II

This dissertation presents the design, modeling, simulation and evaluation of distributed energy resources (DER) consisting of photovoltaics (PV), wind turbines, batteries, a PEM fuel cell and supercapacitors. The distributed energy resources installed at UMass Lowell consist of the following: 2.5kW PV, 44kWhr lead acid batteries and 1500W, 500W & 300W wind turbines, which were installed before year 2000. Recently added to that are the following: 10.56 kW PV array, 2.4 kW wind turbine, 29 kWhr Lead acid batteries, a 1.2 kW PEM fuel cell and 4-140F supercapacitors. Each newly added energy resource has been designed, modeled, simulated and evaluated before its integration into the existing PV/Wind grid-connected system. The Mathematical and Simulink model of each system was derived and validated by comparing the simulated and experimental results. The Simulated results of energy generated from a 10.56kW PV system are in good agreement with the experimental results. A detailed electrical model of a 2.4kW wind turbine system equipped with a permanent magnet generator, diode rectifier, boost converter and inverter is presented. The analysis of the results demonstrates the effectiveness of the constructed simulink model, and can be used to predict the performance of the wind turbine. It was observed that a PEM fuel cell has a very fast response to load changes. Moreover, the model has validated the actual operation of the PEM fuel cell, showing that the simulated results in Matlab Simulink are consistent with the experimental results. The equivalent mathematical equation, derived from an electrical model of the supercapacitor, is used to simulate its voltage response. The model is completely capable of simulating its voltage behavior, and can predict the charge time and discharge time of voltages on the supercapacitor. The bi-directional dc-dc converter was designed in order to connect the 48V battery bank storage to the 24V battery bank storage. This connection was needed in order to increase the reliability of the DER system. Furthermore, the new computer-based Data Acquisition (DAQ) system for the DER has been designed and installed. The DAQ system is an important component in PC-based measurement, which is used in acquiring and storing data. The design and installation of signal conditioning improve the accuracy, effectiveness and safety of measurements, because of capabilities such as amplifications, isolation, and filtering. A Labview program was the software used to interface and communicate between the DAQ devices and the personal computer. The overall simulink model of the DER system is presented in the last chapter. The simulink model is discussed, and the discussion explains the operation of a grid connected DER. This model can be used as the basis or future reference for designs and installations of DER projects. This model can also be used in converting the DER grid connected system into a Smart Grid system, and that will be the next potential research work to explore.

Human Pol ζ purified with accessory subunits is active in translesion DNA synthesis and complements Pol η in cisplatin bypass

PubMed Central

Lee, Young-Sam; Gregory, Mark T.; Yang, Wei

2014-01-01

DNA polymerase ζ (Pol ζ) is a eukaryotic B-family DNA polymerase that specializes in translesion synthesis and is essential for normal embryogenesis. At a minimum, Pol ζ consists of a catalytic subunit Rev3 and an accessory subunit Rev7. Mammalian Rev3 contains >3,000 residues and is twice as large as the yeast homolog. To date, no vertebrate Pol ζ has been purified for biochemical characterization. Here we report purification of a series of human Rev3 deletion constructs expressed in HEK293 cells and identification of a minimally catalytically active human Pol ζ variant. With a tagged form of an active Pol ζ variant, we isolated two additional accessory subunits of human Pol ζ, PolD2 and PolD3. The purified four-subunit Pol ζ4 (Rev3–Rev7–PolD2–PolD3) is much more efficient and more processive at bypassing a 1,2-intrastrand d(GpG)-cisplatin cross-link than the two-subunit Pol ζ2 (Rev3–Rev7). We show that complete bypass of cisplatin lesions requires Pol η to insert dCTP opposite the 3′ guanine and Pol ζ4 to extend the primers. PMID:24449906

Human Pol ζ purified with accessory subunits is active in translesion DNA synthesis and complements Pol η in cisplatin bypass.

PubMed

Lee, Young-Sam; Gregory, Mark T; Yang, Wei

2014-02-25

DNA polymerase ζ (Pol ζ) is a eukaryotic B-family DNA polymerase that specializes in translesion synthesis and is essential for normal embryogenesis. At a minimum, Pol ζ consists of a catalytic subunit Rev3 and an accessory subunit Rev7. Mammalian Rev3 contains >3,000 residues and is twice as large as the yeast homolog. To date, no vertebrate Pol ζ has been purified for biochemical characterization. Here we report purification of a series of human Rev3 deletion constructs expressed in HEK293 cells and identification of a minimally catalytically active human Pol ζ variant. With a tagged form of an active Pol ζ variant, we isolated two additional accessory subunits of human Pol ζ, PolD2 and PolD3. The purified four-subunit Pol ζ4 (Rev3-Rev7-PolD2-PolD3) is much more efficient and more processive at bypassing a 1,2-intrastrand d(GpG)-cisplatin cross-link than the two-subunit Pol ζ2 (Rev3-Rev7). We show that complete bypass of cisplatin lesions requires Pol η to insert dCTP opposite the 3' guanine and Pol ζ4 to extend the primers.

Eine selbstkonsistente Carleman Linearisierung zur Analyse von Oszillatoren

NASA Astrophysics Data System (ADS)

Weber, Harry; Mathis, Wolfgang

2017-09-01

Die Analyse nichtlinearer dynamischer Schaltungen ist bis heute eine herausfordernde Aufgabe, da nur selten analytische Lösungen angegeben werden können. Daher wurden eine Vielzahl von Methoden entwickelt, um eine qualitative oder quantitative Näherung für die Lösungen der Netzwerkgleichung zu erhalten. Oftmals wird beispielsweise eine Kleinsignalanalyse mit Hilfe einer Taylorreihe in einem Arbeitspunkt durchgeführt, die nach den Gliedern erster Ordnung abgebrochen wird. Allerdings ist diese Linearisierung nur in der Nähe des stabilen Arbeitspunktes für hyperbolische Systeme gültig. Besonders für die Analyse des dynamischen Verhaltens von Oszillatoren treten jedoch nicht-hyperbolische Systeme auf, sodass diese Methode nicht angewendet werden kann Mathis (2000). Carleman hat gezeigt, dass nichtlineare Differentialgleichungen mit polynomiellen Nichtlinearitäten in ein unendliches System von linearen Differentialgleichungen transformiert werden können Carleman (1932). Wird das unendlichdimensionale Gleichungssystem für numerische Zwecke abgebrochen, kann bei Oszillatoren der Übergang in eine stationäre Schwingung (Grenzzyklus) nicht wiedergegeben werden. In diesem Beitrag wird eine selbstkonsistente Carleman Linearisierung zur Untersuchung von Oszillatoren vorgestellt, die auch dann anwendbar ist, wenn die Nichtlinearitäten keinen Polynomen entsprechen. Anstelle einer linearen Näherung um einen Arbeitspunkt, erfolgt mit Hilfe der Carleman Linearisierung eine Approximation auf einem vorgegebenen Gebiet. Da es jedoch mit der selbstkonsistenten Technik nicht möglich ist, das stationäre Verhalten von Oszillatoren zu beschreiben, wird die Berechnung einer Poincaré-Abbildung durchgeführt. Mit dieser ist eine anschließende Analyse des Oszillators möglich.

Catalytic properties of RNA polymerases IV and V: accuracy, nucleotide incorporation and rNTP/dNTP discrimination

PubMed Central

Marasco, Michelle; Li, Weiyi; Lynch, Michael

2017-01-01

Abstract All eukaryotes have three essential nuclear multisubunit RNA polymerases, abbreviated as Pol I, Pol II and Pol III. Plants are remarkable in having two additional multisubunit RNA polymerases, Pol IV and Pol V, which synthesize noncoding RNAs that coordinate RNA-directed DNA methylation for silencing of transposons and a subset of genes. Based on their subunit compositions, Pols IV and V clearly evolved as specialized forms of Pol II, but their catalytic properties remain undefined. Here, we show that Pols IV and V differ from one another, and Pol II, in nucleotide incorporation rate, transcriptional accuracy and the ability to discriminate between ribonucleotides and deoxyribonucleotides. Pol IV transcription is considerably more error-prone than Pols II or V, which may be tolerable in its synthesis of short RNAs that serve as precursors for siRNAs targeting non-identical members of transposon families. By contrast, Pol V exhibits high fidelity transcription, similar to Pol II, suggesting a need for Pol V transcripts to faithfully reflect the DNA sequence of target loci to which siRNA–Argonaute silencing complexes are recruited. PMID:28977461

Constant envelope OFDM scheme for 6PolSK-QPSK

NASA Astrophysics Data System (ADS)

Li, Yupeng; Ding, Ding

2018-03-01

A constant envelope OFDM scheme with phase modulator (PM-CE-OFDM) for 6PolSK-QPSK modulation was demonstrated. Performance under large fiber launch power is measured to check its advantages in counteracting fiber nonlinear impairments. In our simulation, PM-CE-OFDM, RF-assisted constant envelope OFDM (RF-CE-OFDM) and conventional OFDM (Con-OFDM) are transmitted through 80 km standard single mode fiber (SSMF) single channel and WDM system. Simulation results confirm that PM-CE-OFDM has best performance in resisting fiber nonlinearity. In addition, benefiting from the simple system structure, the complexity and cost of PM-CE-OFDM system could be reduced effectively.

Airbag-Systeme

NASA Astrophysics Data System (ADS)

Kramer, Florian

Heutige Pkw sind zum Schutz der Insassen bei Frontalkollisionen zu etwa 90 % fahrerseitig und zu ca. 70 % auf der Beifahrerseite mit Airbags ausgestattet, während die Seiten-Airbags zum Schutz des Kopfes und des Thorax von Insassen bei Seitenkollisionen nur mit ungefähr 40 bis 50% vertreten sind [1]. Weitere Schutzmaßnahmen wie Fuß- und Fond-Airbags befinden sich im Entwicklungsstadium, ihr Einsatz in der Serie ist umstritten und wird sich, wenn überhaupt, nur in Einzelfällen durchsetzen. In Bild C3-1 sind Airbags dargestellt, die heute serienmäßig in Pkw anzutreffen sind.

Incorporation of charge transfer into the explicit polarization fragment method by grand canonical density functional theory.

PubMed

Isegawa, Miho; Gao, Jiali; Truhlar, Donald G

2011-08-28

Molecular fragmentation algorithms provide a powerful approach to extending electronic structure methods to very large systems. Here we present a method for including charge transfer between molecular fragments in the explicit polarization (X-Pol) fragment method for calculating potential energy surfaces. In the conventional X-Pol method, the total charge of each fragment is preserved, and charge transfer between fragments is not allowed. The description of charge transfer is made possible by treating each fragment as an open system with respect to the number of electrons. To achieve this, we applied Mermin's finite temperature method to the X-Pol wave function. In the application of this method to X-Pol, the fragments are open systems that partially equilibrate their number of electrons through a quasithermodynamics electron reservoir. The number of electrons in a given fragment can take a fractional value, and the electrons of each fragment obey the Fermi-Dirac distribution. The equilibrium state for the electrons is determined by electronegativity equalization with conservation of the total number of electrons. The amount of charge transfer is controlled by re-interpreting the temperature parameter in the Fermi-Dirac distribution function as a coupling strength parameter. We determined this coupling parameter so as to reproduce the charge transfer energy obtained by block localized energy decomposition analysis. We apply the new method to ten systems, and we show that it can yield reasonable approximations to potential energy profiles, to charge transfer stabilization energies, and to the direction and amount of charge transferred. © 2011 American Institute of Physics

Incorporation of charge transfer into the explicit polarization fragment method by grand canonical density functional theory

PubMed Central

Isegawa, Miho; Gao, Jiali; Truhlar, Donald G.

2011-01-01

Molecular fragmentation algorithms provide a powerful approach to extending electronic structure methods to very large systems. Here we present a method for including charge transfer between molecular fragments in the explicit polarization (X-Pol) fragment method for calculating potential energy surfaces. In the conventional X-Pol method, the total charge of each fragment is preserved, and charge transfer between fragments is not allowed. The description of charge transfer is made possible by treating each fragment as an open system with respect to the number of electrons. To achieve this, we applied Mermin's finite temperature method to the X-Pol wave function. In the application of this method to X-Pol, the fragments are open systems that partially equilibrate their number of electrons through a quasithermodynamics electron reservoir. The number of electrons in a given fragment can take a fractional value, and the electrons of each fragment obey the Fermi–Dirac distribution. The equilibrium state for the electrons is determined by electronegativity equalization with conservation of the total number of electrons. The amount of charge transfer is controlled by re-interpreting the temperature parameter in the Fermi–Dirac distribution function as a coupling strength parameter. We determined this coupling parameter so as to reproduce the charge transfer energy obtained by block localized energy decomposition analysis. We apply the new method to ten systems, and we show that it can yield reasonable approximations to potential energy profiles, to charge transfer stabilization energies, and to the direction and amount of charge transferred. PMID:21895159

Subunit Compositions of the RNA-Silencing Enzymes Pol IV and Pol V Reveal Their Origins as Specialized Forms of RNA Polymerase II

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

Ream, Thomas S.; Haag, J. R.; Wierzbicki, A. T.

2009-01-30

In addition to RNA polymerases I, II and III, which are multi-subunit RNA polymerases found in all eukaryotes, plants have catalytic subunits for two additional nuclear RNA polymerases, abbreviated as Pol IV and Pol V (formerly Pol IVa and Pol IVb, respectively). Pol IV and Pol V play non-redundant roles in siRNA-directed DNA methylation and gene silencing pathways.

Spatial and Functional Relationships Among Pol V-Associated loci, Pol IV-Dependent siRNAs, and Cytosine Methylation in the Arabidopsis Epigenome

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

Wierzbicki, A. T.; Cocklin, Ross; Mayampurath, Anoop

2012-08-15

Multisubunit RNA polymerases IV and V (Pols IV and V) mediate RNA-directed DNA methylation and transcriptional silencing of retrotransposons and heterochromatic repeats in plants. We identified genomic sites of Pol V occupancy in parallel with siRNA deep sequencing and methylcytosine mapping, comparing wild-type plants with mutants defective for Pol IV, Pol V, or both Pols IV and V. Approximately 60% of Pol V-associated regions encompass regions of 24-nucleotide (nt) siRNA complementarity and cytosine methylation, consistent with cytosine methylation being guided by base-pairing of Pol IV-dependent siRNAs with Pol V transcripts. However, 27% of Pol V peaks do not overlap sitesmore » of 24-nt siRNA biogenesis or cytosine methylation, indicating that Pol V alone does not specify sites of cytosine methylation. Surprisingly, the number of methylated CHH motifs, a hallmark of RNA-directed de novo methylation, is similar in wild-type plants and Pol IV or Pol V mutants. In the mutants, methylation is lost at 50%-60% of the CHH sites that are methylated in the wild type but is gained at new CHH positions, primarily in pericentromeric regions. These results indicate that Pol IV and Pol V are not required for cytosine methyltransferase activity but shape the epigenome by guiding CHH methylation to specific genomic sites.« less

Quantum Statistics of the Toda Oscillator in the Wigner Function Formalism

NASA Astrophysics Data System (ADS)

Vojta, Günter; Vojta, Matthias

Classical and quantum mechanical Toda systems (Toda molecules, Toda lattices, Toda quantum fields) recently found growing interest as nonlinear systems showing solitons and chaos. In this paper the statistical thermodynamics of a system of quantum mechanical Toda oscillators characterized by a potential energy V(q) = Vo cos h q is treated within the Wigner function formalism (phase space formalism of quantum statistics). The partition function is given as a Wigner- Kirkwood series expansion in terms of powers of h2 (semiclassical expansion). The partition function and all thermodynamic functions are written, with considerable exactness, as simple closed expressions containing only the modified Hankel functions Ko and K1 of the purely imaginary argument i with = Vo/kT.Translated AbstractQuantenstatistik des Toda-Oszillators im Formalismus der Wigner-FunktionKlassische und quantenmechanische Toda-Systeme (Toda-Moleküle, Toda-Gitter, Toda-Quantenfelder) haben als nichtlineare Systeme mit Solitonen und Chaos in jüngster Zeit zunehmend an Interesse gewonnen. Wir untersuchen die statistische Thermodynamik eines Systems quantenmechanischer Toda-Oszillatoren, die durch eine potentielle Energie der Form V(q) = Vo cos h q charakterisiert sind, im Formalismus der Wigner-Funktion (Phasenraum-Formalismus der Quantenstatistik). Die Zustandssumme wird als Wigner-Kirkwood-Reihe nach Potenzen von h2 (semiklassische Entwicklung) dargestellt, und aus ihr werden die thermodynamischen Funktionen berechnet. Sämtliche Funktionen sind durch einfache geschlossene Formeln allein mit den modifizierten Hankel-Funktionen Ko und K1 des rein imaginären Arguments i mit = Vo/kT mit großer Genauigkeit darzustellen.

Inverter Anti-Islanding with Advanced Grid Support in Single- and Multi-Inverter Islands

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

Hoke, Andy

As PV and other DER systems are connected to the grid at increased penetration levels, island detection may become more challenging for two reasons: 1. In islands containing many DERs, active inverter-based anti-islanding methods may have more difficulty detecting islands because each individual inverter's efforts to detect the island may be interfered with by the other inverters in the island. 2. The increasing numbers of DERs are leading to new requirements that DERs ride through grid disturbances and even actively try to regulate grid voltage and frequency back towards nominal operating conditions. These new grid support requirements may directly ormore » indirectly interfere with anti-islanding controls. This report describes a series of tests designed to examine the impacts of both grid support functions and multi-inverter islands on anti-islanding effectiveness.« less

Catalytic properties of RNA polymerases IV and V: accuracy, nucleotide incorporation and rNTP/dNTP discrimination.

PubMed

Marasco, Michelle; Li, Weiyi; Lynch, Michael; Pikaard, Craig S

2017-11-02

All eukaryotes have three essential nuclear multisubunit RNA polymerases, abbreviated as Pol I, Pol II and Pol III. Plants are remarkable in having two additional multisubunit RNA polymerases, Pol IV and Pol V, which synthesize noncoding RNAs that coordinate RNA-directed DNA methylation for silencing of transposons and a subset of genes. Based on their subunit compositions, Pols IV and V clearly evolved as specialized forms of Pol II, but their catalytic properties remain undefined. Here, we show that Pols IV and V differ from one another, and Pol II, in nucleotide incorporation rate, transcriptional accuracy and the ability to discriminate between ribonucleotides and deoxyribonucleotides. Pol IV transcription is considerably more error-prone than Pols II or V, which may be tolerable in its synthesis of short RNAs that serve as precursors for siRNAs targeting non-identical members of transposon families. By contrast, Pol V exhibits high fidelity transcription, similar to Pol II, suggesting a need for Pol V transcripts to faithfully reflect the DNA sequence of target loci to which siRNA-Argonaute silencing complexes are recruited. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

A RecA Protein Surface Required for Activation of DNA Polymerase V

PubMed Central

Gruber, Angela J.; Erdem, Aysen L.; Sabat, Grzegorz; Karata, Kiyonobu; Jaszczur, Malgorzata M.; Vo, Dan D.; Olsen, Tayla M.; Woodgate, Roger; Goodman, Myron F.; Cox, Michael M.

2015-01-01

DNA polymerase V (pol V) of Escherichia coli is a translesion DNA polymerase responsible for most of the mutagenesis observed during the SOS response. Pol V is activated by transfer of a RecA subunit from the 3'-proximal end of a RecA nucleoprotein filament to form a functional complex called DNA polymerase V Mutasome (pol V Mut). We identify a RecA surface, defined by residues 112-117, that either directly interacts with or is in very close proximity to amino acid residues on two distinct surfaces of the UmuC subunit of pol V. One of these surfaces is uniquely prominent in the active pol V Mut. Several conformational states are populated in the inactive and active complexes of RecA with pol V. The RecA D112R and RecA D112R N113R double mutant proteins exhibit successively reduced capacity for pol V activation. The double mutant RecA is specifically defective in the ATP binding step of the activation pathway. Unlike the classic non-mutable RecA S117F (recA1730), the RecA D112R N113R variant exhibits no defect in filament formation on DNA and promotes all other RecA activities efficiently. An important pol V activation surface of RecA protein is thus centered in a region encompassing amino acid residues 112, 113, and 117, a surface exposed at the 3'-proximal end of a RecA filament. The same RecA surface is not utilized in the RecA activation of the homologous and highly mutagenic RumA'2B polymerase encoded by the integrating-conjugative element (ICE) R391, indicating a lack of structural conservation between the two systems. The RecA D112R N113R protein represents a new separation of function mutant, proficient in all RecA functions except SOS mutagenesis. PMID:25811184

Introduction of a Diagnosis Related Groups’ Case Flat Rate System: Hopes and Fears (einfuerhrng eines drg-fallpauschalensystems - hoffnungen und aengste)

DTIC Science & Technology

2000-06-01

Anwendung und Pflege des neuen Systems dienen soil, wenn die entscheidenden Vorgaben bereits durch die Deckelung gegeben sind. Oder denkt man an den...Software und die da- mit verbundenen Lizenzgebuhren, sondern auch in der Folge um die Schulung der Mitarbeiter sowie die Pflege und Weiterentwicklung...sung an die medizinische Entwicklung" sowie von "Verfahren zur laufen- den Pflege des VergOtungssystems" gesprochen. Es mossen jedoch klare

Design Flexibility for Uncertain Distributed Generation from Photovoltaics

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

Palmintier, Bryan; Krishnamurthy, Dheepak; Wu, Hongyu

2016-12-12

Uncertainty in the future adoption patterns for distributed energy resources (DERs) introduces a challenge for electric distribution system planning. This paper explores the potential for flexibility in design - also known as real options - to identify design solutions that may never emerge when future DER patterns are treated as deterministic. A test case for storage system design with uncertain distributed generation for solar photovoltaics (DGPV) demonstrates this approach and is used to study sensitivities to a range of techno-economic assumptions.

A major role of DNA polymerase δ in replication of both the leading and lagging DNA strands

PubMed Central

Prakash, Louise; Prakash, Satya

2015-01-01

SUMMARY Genetic studies with S. cerevisiae Polδ (pol3-L612M) and Polε (pol2-M644G) mutant alleles, each of which display a higher rate for the generation of a specific mismatch, have led to the conclusion that Polε is the primary leading strand replicase and that Polδ is restricted to replicating the lagging strand template. Contrary to this widely accepted view, here we show that Polδ plays a major role in the replication of both DNA strands, and that the paucity of pol3-L612M generated errors on the leading strand results from their more proficient removal. Thus, the apparent lack of Polδ contribution to leading strand replication is due to differential mismatch removal rather than differential mismatch generation. Altogether, our genetic studies with Pol3 and Pol2 mutator alleles support the conclusion that Polδ, and not Polε, is the major DNA polymerase for carrying out both leading and lagging DNA synthesis. PMID:26145172

Estimation of Melt Pond Fractions on First Year Sea Ice Using Compact Polarization SAR

NASA Astrophysics Data System (ADS)

Li, Haiyan; Perrie, William; Li, Qun; Hou, Yijun

2017-10-01

Melt ponds are a common feature on Arctic sea ice. They are linked to the sea ice surface albedo and transmittance of energy to the ocean from the atmosphere and thus constitute an important process to parameterize in Arctic climate models and simulations. This paper presents a first attempt to retrieve the melt pond fraction from hybrid-polarized compact polarization (CP) SAR imagery, which has wider swath and shorter revisit time than the quad-polarization systems, e.g., from RADARSAT-2 (RS-2). The co-polarization (co-pol) ratio has been verified to provide estimates of melt pond fractions. However, it is a challenge to link CP parameters and the co-pol ratio. The theoretical possibility is presented, for making this linkage with the CP parameter C22/C11 (the ratio between the elements of the coherence matrix of CP SAR) for melt pond detection and monitoring with the tilted-Bragg scattering model for the ocean surface. The empirical transformed formulation, denoted as the "compact polarization and quad-pol" ("CPQP") model, is proposed, based on 2062 RS-2 quad-pol SAR images, collocated with in situ measurements. We compared the retrieved melt pond fraction with CP parameters simulated from quad-pol SAR data with results retrieved from the co-pol ratio from quad-pol SAR observations acquired during the Arctic-Ice (Arctic-Ice Covered Ecosystem in a Rapidly Changing Environment) field project. The results are shown to be comparable for observed melt pond measurements in spatial and temporal distributions. Thus, the utility of CP mode SAR for melt pond fraction estimation on first year level ice is presented.

Mediator-regulated transcription through the +1 nucleosome.

PubMed

Nock, Adam; Ascano, Janice M; Barrero, Maria J; Malik, Sohail

2012-12-28

Many genes are regulated at the level of a Pol II that is recruited to a nucleosome-free region upstream of the +1 nucleosome. How the Mediator coactivator complex, which functions at multiple steps, affects transcription through the promoter proximal region, including this nucleosome, remains largely unaddressed. We have established a fully defined in vitro assay system to delineate mechanisms for Pol II transit across the +1 nucleosome. Our results reveal cooperative functions of multiple cofactors, particularly of Mediator and elongation factor SII, in transcribing into this nucleosome. This is achieved, in part, through an unusual activity of SII that alters the intrinsic catalytic properties of promoter-proximal Pol II and, in concert with the Mediator, leads to enhancement in transcription of nucleosomal DNA. Our data provide additional mechanistic bases for Mediator function after recruitment of Pol II and, potentially, for regulation of genes controlled via nucleosome-mediated promoter-proximal pausing. Copyright © 2012 Elsevier Inc. All rights reserved.

van der Waals forces in density functional theory: a review of the vdW-DF method

DOE PAGES

Berland, Kristian; Cooper, Valentino R.; Lee, Kyuho; ...

2015-05-15

We review a density functional theory (DFT) that accounts for van der Waals (vdW) interactions in condensed matter, materials physics, chemistry, and biology. The insights that led to the construction of the Rutgers–Chalmers van der Waals density functional (vdW-DF) are presented with the aim of giving a historical perspective, while also emphasizing more recent efforts which have sought to improve its accuracy. In addition to technical details, we discuss a range of recent applications that illustrate the necessity of including dispersion interactions in DFT. This review highlights the value of the vdW-DF method as a general-purpose method, not only formore » dispersion bound systems, but also in densely packed systems where these types of interactions are traditionally thought to be negligible.« less

Auf dem Weg zur digitalen Fakultät - moderne IT Infrastruktur am Beispiel des Physik-Departments der TU München

NASA Astrophysics Data System (ADS)

Homolka, Josef

Der Geschäftsbetrieb einer Universität ist durch zunehmende Digitalisierung und Nutzung elektronischer Medien gekennzeichnet. Die Einführung immer leistungsfähigerer zentraler IT-Systeme führt zu einer komplexen Vielfalt heterogener Benutzer- und Administrationsschnittstellen. Zur Schaffung einer umfassenden benutzerfreundlichen und nahtlosen IT-Infrastruktur ist die Beteiligung aller organisatorischen Einheiten und Ebenen erforderlich. Am Physik-Departement der Technischen Universität München wurden unter Integration eigener Ressourcen mit zentralen Ressourcen, die im Rahmen des IntegraTUM Projektes entwickelt und bereitgestellt wurden, existierende Dienste weiterentwickelt und neue Angebote aufgebaut. Das System, bestehend aus den Komponenten Netzwerk, Arbeitsplatzrechner, Serverinfrastruktur, E-Mail-Service, WWWDienst, Datenhaltung und Software wurde für die Nutzerkreise Studenten und Mitarbeiter im Hinblick auf Anwenderfreundlichkeit und nahtlosen Zugriff optimiert.

Evaluation der zentralen TUM-Lernplattform

NASA Astrophysics Data System (ADS)

Schulze, Elvira; Baume, Matthias; Graf, Stephan; Gergintchev, Ivan

Die Notwendigkeit der Qualitätssicherung und -kontrolle für innovative universitäre Lehr-/Lernszenarien ist in der Praxis unbestritten. Die Wirksamkeit der Einführung der zentralen Lernplattform CLIX Campus der imc AG an der TUM wurde mittels quantitativer und qualitativer Evaluation überprüft. Als statistische Bewertungsgrundlage wurde der Erreichungsgrad bestimmter Projektziele herangezogen. Aufbauend auf den theoretischen Grundlagen der Evaluation von Bildungsangeboten gibt diese Studie Aufschluss über die Ergebnisse der Datenerhebungen sowie die Einschätzung der Plattform aus Nutzersicht und belegt die wesentliche Bedeutung der durchgängigen IT-Infrastruktur und speziell der einheitlichen Verfügbarkeit der eLearning Angebote.

Characterization of Mycobacterium smegmatis PolD2 and PolD1 as RNA/DNA polymerases homologous to the POL domain of bacterial DNA ligase D

PubMed Central

Zhu, Hui; Bhattarai, Hitesh; Yan, Han-Guang; Shuman, Stewart; Glickman, Michael S.

2013-01-01

Mycobacteria exploit nonhomologous end-joining (NHEJ) to repair DNA double-strand breaks. The core NHEJ machinery comprises the homodimeric DNA end-binding protein Ku and DNA ligase D (LigD), a modular enzyme composed of a C-terminal ATP-dependent ligase domain (LIG), a central 3’-phosphoesterase domain (PE), and an N-terminal polymerase domain (POL). LigD POL is proficient at adding templated and nontemplated deoxynucleotide and ribonucleotides to DNA ends in vitro and is the catalyst in vivo of unfaithful NHEJ events involving nontemplated single-nucleotide additions to blunt DSB ends. Here, we identify two mycobacterial proteins, PolD1 and PolD2, as stand-alone homologs of the LigD POL domain. Biochemical characterization of PolD1 and PolD2 shows that they resemble LigD POL in their monomeric quaternary structures, their ability to add templated and nontemplated nucleotides to primer-templates and blunt ends, and their preference for rNTPs versus dNTPs. Deletion of polD1, polD2, or both, in an M. smegmatis strain carrying an inactivating mutation in LigD POL failed to reveal a role for PolD1 or PolD2 in templated nucleotide additions during NHEJ of 5’-overhang DSBs or in clastogen resistance. Whereas our results document the existence and characteristics of new stand-alone members of the LigD POL family of RNA/DNA polymerases, they imply that other polymerases can perform fill-in synthesis during mycobacterial NHEJ. PMID:23198659

Defect of Fe-S cluster binding by DNA polymerase δ in yeast suppresses UV-induced mutagenesis, but enhances DNA polymerase ζ - dependent spontaneous mutagenesis.

PubMed

Stepchenkova, E I; Tarakhovskaya, E R; Siebler, H M; Pavlov, Y I

2017-01-01

Eukaryotic genomes are duplicated by a complex machinery, utilizing high fidelity replicative B-family DNA polymerases (pols) α, δ and ε. Specialized error-prone pol ζ, the fourth B-family member, is recruited when DNA synthesis by the accurate trio is impeded by replication stress or DNA damage. The damage tolerance mechanism dependent on pol ζ prevents DNA/genome instability and cell death at the expense of increased mutation rates. The pol switches occurring during this specialized replication are not fully understood. The loss of pol ζ results in the absence of induced mutagenesis and suppression of spontaneous mutagenesis. Disruption of the Fe-S cluster motif that abolish the interaction of the C-terminal domain (CTD) of the catalytic subunit of pol ζ with its accessory subunits, which are shared with pol δ, leads to a similar defect in induced mutagenesis. Intriguingly, the pol3-13 mutation that affects the Fe-S cluster in the CTD of the catalytic subunit of pol δ also leads to defective induced mutagenesis, suggesting the possibility that Fe-S clusters are essential for the pol switches during replication of damaged DNA. We confirmed that yeast strains with the pol3-13 mutation are UV-sensitive and defective in UV-induced mutagenesis. However, they have increased spontaneous mutation rates. We found that this increase is dependent on functional pol ζ. In the pol3-13 mutant strain with defective pol δ, there is a sharp increase in transversions and complex mutations, which require functional pol ζ, and an increase in the occurrence of large deletions, whose size is controlled by pol ζ. Therefore, the pol3-13 mutation abrogates pol ζ-dependent induced mutagenesis, but allows for pol ζ recruitment for the generation of spontaneous mutations and prevention of larger deletions. These results reveal differential control of the two major types of pol ζ-dependent mutagenesis by the Fe-S cluster present in replicative pol δ. Copyright © 2016 Elsevier B.V. All rights reserved.

Der p 5 Crystal Structure Provides Insight into the Group 5 Dust Mite Allergens

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

Mueller, G.; Gosavi, R; Krahn, J

2010-01-01

Group 5 allergens from house dust mites elicit strong IgE antibody binding in mite-allergic patients. The structure of Der p 5 was determined by x-ray crystallography to better understand the IgE epitopes, to investigate the biologic function in mites, and to compare with the conflicting published Blo t 5 structures, designated 2JMH and 2JRK in the Protein Data Bank. Der p 5 is a three-helical bundle similar to Blo t 5, but the interactions of the helices are more similar to 2JMH than 2JRK. The crystallographic asymmetric unit contains three dimers of Der p 5 that are not exactly alike.more » Solution scattering techniques were used to assess the multimeric state of Der p 5 in vitro and showed that the predominant state was monomeric, similar to Blo t 5, but larger multimeric species are also present. In the crystal, the formation of the Der p 5 dimer creates a large hydrophobic cavity of {approx}3000 {angstrom}{sup 3} that could be a ligand-binding site. Many allergens are known to bind hydrophobic ligands, which are thought to stimulate the innate immune system and have adjuvant-like effects on IgE-mediated inflammatory responses.« less

Antinociceptive activity of Hypericum caprifoliatum and Hypericum polyanthemum (Guttiferae).

PubMed

Viana, A F; Heckler, A P; Fenner, R; Rates, S M K

2003-05-01

The aim of the present study was to assess the analgesic activity of the aerial parts of two Hypericum species native to Southern Brazil, H. caprifoliatum and H. polyanthemum. The antinociceptive effect of the H. polyanthemum cyclohexane extract (POL; 180 mg/kg) and of the H. caprifoliatum methanol (MET) and cyclohexane (CH) extracts (90 mg/kg) was evaluated in the hot-plate (ip and po) and writhing (po) tests using male Swiss CF1 mice weighing 22-27 g (N = 10 per group). All extracts displayed antinociceptive effects in the hot-plate test (MET ip = 48%, MET po = 39%, CH ip = 27%, CH po = 50%, POL ip = 74%, and POL po = 49% compared to control). Pretreatment with naloxone (2.5 mg/kg, sc) abolished the effects of CH and POL, and partially prevented the analgesia induced by MET administered by the ip (but not by the po) route. POL and CH (po) significantly reduced the number of writhes induced by acetic acid, while MET was ineffective in this regard. We conclude that the antinociceptive effects of the H. caprifoliatum (CH) and H. polyanthemum (POL) hexane extracts seem to be mediated by the opioid system. Moreover, the antinociceptive activity of the H. caprifoliatum MET extract seems to depend on at least two chemical substances (or groups of substances) with distinct pharmacokinetic profiles and mechanisms of action. Only the naloxone-insensitive component of MET activity showed good bioavailability following oral administration.

Facilitated recycling protects human RNA polymerase III from repression by Maf1 in vitro.

PubMed

Cabart, Pavel; Lee, JaeHoon; Willis, Ian M

2008-12-26

Yeast cells synthesize approximately 3-6 million molecules of tRNA every cell cycle at a rate of approximately 2-4 transcripts/gene/s. This high rate of transcription is achieved through many rounds of reinitiation by RNA polymerase (pol) III on stable DNA-bound complexes of the initiation factor TFIIIB. Studies in yeast have shown that the rate of reinitiation is increased by facilitated recycling, a process that involves the repeated reloading of the polymerase on the same transcription unit. However, when nutrients become limiting or stress conditions are encountered, RNA pol III transcription is rapidly repressed through the action of the conserved Maf1 protein. Here we examine the relationship between Maf1-mediated repression and facilitated recycling in a human RNA pol III in vitro system. Using an immobilized template transcription assay, we demonstrate that facilitated recycling is conserved from yeast to humans. We assessed the ability of recombinant human Maf1 to inhibit different steps in transcription before and after preinitiation complex assembly. We show that recombinant Maf1 can inhibit the recruitment of TFIIIB and RNA pol III to immobilized templates. However, RNA pol III bound to preinitiation complexes or in elongation complexes is protected from repression by Maf1 and can undergo several rounds of initiation. This indicates that recombinant Maf1 is unable to inhibit facilitated recycling. The data suggest that additional biochemical steps may be necessary for rapid Maf1-dependent repression of RNA pol III transcription.

DNA replication error-induced extinction of diploid yeast.

PubMed

Herr, Alan J; Kennedy, Scott R; Knowels, Gary M; Schultz, Eric M; Preston, Bradley D

2014-03-01

Genetic defects in DNA polymerase accuracy, proofreading, or mismatch repair (MMR) induce mutator phenotypes that accelerate adaptation of microbes and tumor cells. Certain combinations of mutator alleles synergistically increase mutation rates to levels that drive extinction of haploid cells. The maximum tolerated mutation rate of diploid cells is unknown. Here, we define the threshold for replication error-induced extinction (EEX) of diploid Saccharomyces cerevisiae. Double-mutant pol3 alleles that carry mutations for defective DNA polymerase-δ proofreading (pol3-01) and accuracy (pol3-L612M or pol3-L612G) induce strong mutator phenotypes in heterozygous diploids (POL3/pol3-01,L612M or POL3/pol3-01,L612G). Both pol3-01,L612M and pol3-01,L612G alleles are lethal in the homozygous state; cells with pol3-01,L612M divide up to 10 times before arresting at random stages in the cell cycle. Antimutator eex mutations in the pol3 alleles suppress this lethality (pol3-01,L612M,eex or pol3-01,L612G,eex). MMR defects synergize with pol3-01,L612M,eex and pol3-01,L612G,eex alleles, increasing mutation rates and impairing growth. Conversely, inactivation of the Dun1 S-phase checkpoint kinase suppresses strong pol3-01,L612M,eex and pol3-01,L612G,eex mutator phenotypes as well as the lethal pol3-01,L612M phenotype. Our results reveal that the lethal error threshold in diploids is 10 times higher than in haploids and likely determined by homozygous inactivation of essential genes. Pronounced loss of fitness occurs at mutation rates well below the lethal threshold, suggesting that mutator-driven cancers may be susceptible to drugs that exacerbate replication errors.

A New Remote Communications Link to Reduce Residential PV Solar Costs

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

King, Randy; Sugiyama, Rod

Monitoring of PV/DER site production is expensive to install and unreliable. Among third party systems providers, lost communications links are a growing concern. Nearly 20% of links are failing, provisioning is complex, recovery is expensive, production data is lost, and access is fragmented. FleetLink is a new concept in DER system communications, purpose built for lowering the cost of maintaining active contact with residential end user sites and ensuring that production data is reliably available to third party systems providers. Systems providers require accurate, secure system monitoring and reporting of production data and system faults while driving down overall costsmore » to compete effectively. This plug and play, independently operating communications solution lowers the cost of fleet contact from typically .08 dollars-$.12/W down to .02 dollars -.03/W including installation and maintenance expenses. FleetLink establishes a breakthrough in simplicity that facilitates rapid expansion of residential solar by reducing initial capital outlay and lowering installation labor time and skill levels. The solution also facilitates higher DER installation growth rates by driving down maintenance costs and eliminating communications trouble calls. This is accomplished by the FleetLink’s unique network technology that enables dynamic network configuration for fast changes, and active, self-healing DER site contact for uptime assurance. Using an open source network framework with proprietary, application specific enhancements, FleetLink independently manages connectivity, security, recovery, grid control communications, and fleet expansion while presenting a compliant SunSpec interface to the third party operations centers. The net system cost savings of at least .05 dollars/W supports the SunShot cost goals and the flexibility and scalability of the solution accelerates the velocity and ubiquitous adoption of solar.« less

Prediction of intrinsic two-dimensional ferroelectrics in In2Se3 and other III2-VI3 van der Waals materials.

PubMed

Ding, Wenjun; Zhu, Jianbao; Wang, Zhe; Gao, Yanfei; Xiao, Di; Gu, Yi; Zhang, Zhenyu; Zhu, Wenguang

2017-04-07

Interest in two-dimensional (2D) van der Waals materials has grown rapidly across multiple scientific and engineering disciplines in recent years. However, ferroelectricity, the presence of a spontaneous electric polarization, which is important in many practical applications, has rarely been reported in such materials so far. Here we employ first-principles calculations to discover a branch of the 2D materials family, based on In 2 Se 3 and other III 2 -VI 3 van der Waals materials, that exhibits room-temperature ferroelectricity with reversible spontaneous electric polarization in both out-of-plane and in-plane orientations. The device potential of these 2D ferroelectric materials is further demonstrated using the examples of van der Waals heterostructures of In 2 Se 3 /graphene, exhibiting a tunable Schottky barrier, and In 2 Se 3 /WSe 2 , showing a significant band gap reduction in the combined system. These findings promise to substantially broaden the tunability of van der Waals heterostructures for a wide range of applications.

Prediction of intrinsic two-dimensional ferroelectrics in In2Se3 and other III2-VI3 van der Waals materials

PubMed Central

Ding, Wenjun; Zhu, Jianbao; Wang, Zhe; Gao, Yanfei; Xiao, Di; Gu, Yi; Zhang, Zhenyu; Zhu, Wenguang

2017-01-01

Interest in two-dimensional (2D) van der Waals materials has grown rapidly across multiple scientific and engineering disciplines in recent years. However, ferroelectricity, the presence of a spontaneous electric polarization, which is important in many practical applications, has rarely been reported in such materials so far. Here we employ first-principles calculations to discover a branch of the 2D materials family, based on In2Se3 and other III2-VI3 van der Waals materials, that exhibits room-temperature ferroelectricity with reversible spontaneous electric polarization in both out-of-plane and in-plane orientations. The device potential of these 2D ferroelectric materials is further demonstrated using the examples of van der Waals heterostructures of In2Se3/graphene, exhibiting a tunable Schottky barrier, and In2Se3/WSe2, showing a significant band gap reduction in the combined system. These findings promise to substantially broaden the tunability of van der Waals heterostructures for a wide range of applications. PMID:28387225

Prediction of intrinsic two-dimensional ferroelectrics in In2Se3 and other III2-VI3 van der Waals materials

NASA Astrophysics Data System (ADS)

Ding, Wenjun; Zhu, Jianbao; Wang, Zhe; Gao, Yanfei; Xiao, Di; Gu, Yi; Zhang, Zhenyu; Zhu, Wenguang

2017-04-01

Interest in two-dimensional (2D) van der Waals materials has grown rapidly across multiple scientific and engineering disciplines in recent years. However, ferroelectricity, the presence of a spontaneous electric polarization, which is important in many practical applications, has rarely been reported in such materials so far. Here we employ first-principles calculations to discover a branch of the 2D materials family, based on In2Se3 and other III2-VI3 van der Waals materials, that exhibits room-temperature ferroelectricity with reversible spontaneous electric polarization in both out-of-plane and in-plane orientations. The device potential of these 2D ferroelectric materials is further demonstrated using the examples of van der Waals heterostructures of In2Se3/graphene, exhibiting a tunable Schottky barrier, and In2Se3/WSe2, showing a significant band gap reduction in the combined system. These findings promise to substantially broaden the tunability of van der Waals heterostructures for a wide range of applications.

A theoretical approach for estimation of ultimate size of bimetallic nanocomposites synthesized in microemulsion systems

NASA Astrophysics Data System (ADS)

Salabat, Alireza; Saydi, Hassan

2012-12-01

In this research a new idea for prediction of ultimate sizes of bimetallic nanocomposites synthesized in water-in-oil microemulsion system is proposed. In this method, by modifying Tabor Winterton approximation equation, an effective Hamaker constant was introduced. This effective Hamaker constant was applied in the van der Waals attractive interaction energy. The obtained effective van der Waals interaction energy was used as attractive contribution in the total interaction energy. The modified interaction energy was applied successfully to predict some bimetallic nanoparticles, at different mass fraction, synthesized in microemulsion system of dioctyl sodium sulfosuccinate (AOT)/isooctane.

A variation-perturbation method for atomic and molecular interactions. I - Theory. II - The interaction potential and van der Waals molecule for Ne-HF

NASA Astrophysics Data System (ADS)

Gallup, G. A.; Gerratt, J.

1985-09-01

The van der Waals energy between the two parts of a system is a very small fraction of the total electronic energy. In such cases, calculations have been based on perturbation theory. However, such an approach involves certain difficulties. For this reason, van der Waals energies have also been directly calculated from total energies. But such a method has definite limitations as to the size of systems which can be treated, and recently ab initio calculations have been combined with damped semiempirical long-range dispersion potentials to treat larger systems. In this procedure, large basis set superposition errors occur, which must be removed by the counterpoise method. The present investigation is concerned with an approach which is intermediate between the previously considered procedures. The first step in the new approach involves a variational calculation based upon valence bond functions. The procedure includes also the optimization of excited orbitals, and an approximation of atomic integrals and Hamiltonian matrix elements.

Quantum Monte Carlo Simulation of condensed van der Waals Systems

NASA Astrophysics Data System (ADS)

Benali, Anouar; Shulenburger, Luke; Romero, Nichols A.; Kim, Jeongnim; Anatole von Lilienfeld, O.

2012-02-01

Van der Waals forces are as ubiquitous as infamous. While post-Hartree-Fock methods enable accurate estimates of these forces in molecules and clusters, they remain elusive for dealing with many-electron condensed phase systems. We present Quantum Monte Carlo [1,2] results for condensed van der Waals systems. Interatomic many-body contributions to cohesive energies and bulk modulus will be discussed. Numerical evidence is presented for crystals of rare gas atoms, and compared to experiments and methods [3]. Sandia National Laboratories is a multiprogram laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. DoE's National Nuclear Security Administration under Contract No. DE-AC04-94AL85000.[4pt] [1] J. Kim, K. Esler, J. McMinis and D. Ceperley, SciDAC 2010, J. of Physics: Conference series, Chattanooga, Tennessee, July 11 2011 [0pt] [2] QMCPACK simulation suite, http://qmcpack.cmscc.org (unpublished)[0pt] [3] O. A. von Lillienfeld and A. Tkatchenko, J. Chem. Phys. 132 234109 (2010)

Methoden der digitalen Planung

NASA Astrophysics Data System (ADS)

Westkämper, Engelbert; Niemann, Jörg; Warschat, Joachim; Scheer, August-Wilhelm; Thomas, Oliver

Die industrielle Produktion ist das Herz der verarbeitenden Industrie in Deutschland. Mit einem Beitrag von rund 500 Mrd. EUR pro Jahr erwirtschaftet das verarbeitende Gewerbe etwa ein Viertel der gesamtwirtschaftlichen Wertschöpfung in Deutschland. Gemessen am Produktionswert der Gesamtwirtschaft betrug der industrielle Anteil sogar über ein Drittel. Der Erhalt und der Ausbau der Wettbewerbsfähigkeit unter den gegebenen Rahmenbedingungen der globalen Märkte ist eine der größten Herausforderungen der deutschen Wirtschaft [5, 8]. In diesem Beitrag soll - ausgehend von einer Strategie der Ausrüster von Fabriken in einer globalen Produktion - diskutiert werden, wie mit der digitalen Fabrik Potentiale in den Planungs- und Wandlungsprozessen erschlossen werden können.

An epitope-specific DerG-PG70 LEAPS vaccine modulates T cell responses and suppresses arthritis progression in two related murine models of rheumatoid arthritis

PubMed Central

Mikecz, Katalin; Glant, Tibor T.; Markovics, Adrienn; Rosenthal, Kenneth S.; Kurko, Julia; Carambula, Roy E.; Cress, Steve; Steiner, Harold L.; Zimmerman, Daniel H.

2017-01-01

Rheumatoid arthritis (RA) is an autoimmune joint disease maintained by aberrant immune responses involving CD4+ T helper (Th)1 and Th17 cells. In this study, we tested the therapeutic efficacy of Ligand Epitope Antigen Presentation System (LEAPS™) vaccines in two Th1 cell-driven mouse models of RA, cartilage proteoglycan (PG)-induced arthritis (PGIA) and PG G1-domain-induced arthritis (GIA). The immunodominant PG peptide PG70 was attached to a DerG or J immune cell binding peptide, and the DerG-PG70 and J-PG70 LEAPS vaccines were administered to the mice after the onset of PGIA or GIA symptoms. As indicated by significant decreases in visual and histopathological scores of arthritis, the DerG-PG70 vaccine inhibited disease progression in both PGIA and GIA, while the J-PG70 vaccine was ineffective. Splenic CD4+ cells from DerG-PG70-treated mice were diminished in Th1 and Th17 populations but enriched in Th2 and regulatory T (Treg) cells. In vitro spleen cell-secreted and serum cytokines from DerG-PG70-treated mice demonstrated a shift from a pro-inflammatory to an anti-inflammatory/regulatory profile. DerG-PG70 peptide tetramers preferentially bound to CD4+ T-cells of GIA spleen cells. We conclude that the DerG-PG70 vaccine (now designated CEL-4000) exerts its therapeutic effect by interacting with CD4+ cells, which results in an antigen-specific down-modulation of pathogenic T-cell responses in both the PGIA and GIA models of RA. Future studies will need to determine the potential of LEAPS vaccination to provide disease suppression in patients with RA. PMID:28583308

[Management of Pregnancy-Associated Venous Thromboembolism - Current Recommendations].

PubMed

Linnemann, Birgit

2017-06-01

Diagnostik in der Schwangerschaft  Studien belegen den hohen Stellenwert der Kompressionssonografie der Beinvenen plus Duplexsonografie der Beckenvenen in der Diagnostik der Becken- und Beinvenenthrombose auch bei Schwangeren. Perfusionsszintigrafie und CT-Angiografie der Pulmonalarterien sind bei vergleichbarer fötaler Strahlenbelastung gleich aussagekräftig. Aufgrund der mütterlichen Strahlenbelastung favorisieren aktuelle Leitlinien bei fehlender struktureller Lungenerkrankung die Perfusionsszintigrafie als primäre Bildgebung. Es gibt keinen Grund, einer Schwangeren mit Lungenembolieverdacht eine notwendige radiologische Diagnosesicherung vorzuenthalten. Antikoagulation in der Schwangerschaft  Heparine bleiben Antikoagulans der 1. Wahl bei der Behandlung der venöses Thromboembolien (VTE) in der Schwangerschaft. Neue orale Antikoagulantien (NOAK) sind aufgrund ihrer geringen Molekülgröße plazentagängig und daher in der Schwangerschaft kontraindiziert. Peripartales Vorgehen  Zur Minimierung des postpartalen Blutungsrisikos vor der Geburt ist in den letzten Wochen vor der Geburt eine Aufteilung der NMH-Injektion auf 2 Tagesdosen sinnvoll. Bei der Entbindung ist eine interdisziplinäre Abstimmung wichtig. Postpartal kann eine NMH-Therapie fortgesetzt oder Warfarin eingesetzt werden (Kein Phenprocoumon, da es in die Muttermilch übergeht).

CMG helicase and DNA polymerase ε form a functional 15-subunit holoenzyme for eukaryotic leading-strand DNA replication.

PubMed

Langston, Lance D; Zhang, Dan; Yurieva, Olga; Georgescu, Roxana E; Finkelstein, Jeff; Yao, Nina Y; Indiani, Chiara; O'Donnell, Mike E

2014-10-28

DNA replication in eukaryotes is asymmetric, with separate DNA polymerases (Pol) dedicated to bulk synthesis of the leading and lagging strands. Pol α/primase initiates primers on both strands that are extended by Pol ε on the leading strand and by Pol δ on the lagging strand. The CMG (Cdc45-MCM-GINS) helicase surrounds the leading strand and is proposed to recruit Pol ε for leading-strand synthesis, but to date a direct interaction between CMG and Pol ε has not been demonstrated. While purifying CMG helicase overexpressed in yeast, we detected a functional complex between CMG and native Pol ε. Using pure CMG and Pol ε, we reconstituted a stable 15-subunit CMG-Pol ε complex and showed that it is a functional polymerase-helicase on a model replication fork in vitro. On its own, the Pol2 catalytic subunit of Pol ε is inefficient in CMG-dependent replication, but addition of the Dpb2 protein subunit of Pol ε, known to bind the Psf1 protein subunit of CMG, allows stable synthesis with CMG. Dpb2 does not affect Pol δ function with CMG, and thus we propose that the connection between Dpb2 and CMG helps to stabilize Pol ε on the leading strand as part of a 15-subunit leading-strand holoenzyme we refer to as CMGE. Direct binding between Pol ε and CMG provides an explanation for specific targeting of Pol ε to the leading strand and provides clear mechanistic evidence for how strand asymmetry is maintained in eukaryotes.

CMG helicase and DNA polymerase ε form a functional 15-subunit holoenzyme for eukaryotic leading-strand DNA replication

PubMed Central

Langston, Lance D.; Zhang, Dan; Yurieva, Olga; Georgescu, Roxana E.; Finkelstein, Jeff; Yao, Nina Y.; Indiani, Chiara; O’Donnell, Mike E.

2014-01-01

DNA replication in eukaryotes is asymmetric, with separate DNA polymerases (Pol) dedicated to bulk synthesis of the leading and lagging strands. Pol α/primase initiates primers on both strands that are extended by Pol ε on the leading strand and by Pol δ on the lagging strand. The CMG (Cdc45-MCM-GINS) helicase surrounds the leading strand and is proposed to recruit Pol ε for leading-strand synthesis, but to date a direct interaction between CMG and Pol ε has not been demonstrated. While purifying CMG helicase overexpressed in yeast, we detected a functional complex between CMG and native Pol ε. Using pure CMG and Pol ε, we reconstituted a stable 15-subunit CMG–Pol ε complex and showed that it is a functional polymerase–helicase on a model replication fork in vitro. On its own, the Pol2 catalytic subunit of Pol ε is inefficient in CMG-dependent replication, but addition of the Dpb2 protein subunit of Pol ε, known to bind the Psf1 protein subunit of CMG, allows stable synthesis with CMG. Dpb2 does not affect Pol δ function with CMG, and thus we propose that the connection between Dpb2 and CMG helps to stabilize Pol ε on the leading strand as part of a 15-subunit leading-strand holoenzyme we refer to as CMGE. Direct binding between Pol ε and CMG provides an explanation for specific targeting of Pol ε to the leading strand and provides clear mechanistic evidence for how strand asymmetry is maintained in eukaryotes. PMID:25313033

Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation.

PubMed

Ohashi-Doi, Katsuyo; Kito, Hirokazu; Du, Weibin; Nakazawa, Hiroshi; Ipsen, Henrik; Gudmann, Pernille; Lund, Kaare

2017-01-01

In sublingual immunotherapy (SLIT), the immune system is addressed by solubilized allergen that interacts with immunocompetent cells of the oral mucosa, the efficiency of which is governed by 2 main factors of SLIT allergen bioavailability: the allergen concentration and the mucosal contact time. Recently, 3 house dust mite (HDM) SLIT tablets were developed that differ with regard to allergen content, nominal strength (maintenance doses: 6 SQ-HDM/10,000 Japanese Allergen Units [JAU], 12 SQ-HDM/ 20,000 JAU, and 300 IR/57,000 JAU), and formulation (freeze-dried/compressed). Here, the importance of the SLIT tablet formulation for HDM major allergen bioavailability is examined. The HDM major allergen content, tablet disintegration times, and allergen release kinetics were determined. Dissolution kinetics (allergen concentration vs. time) of Der f 1, Der p 1, and Der 2 were measured. Area under the curve (AUC) was used as a surrogate parameter for allergen bioavailability. The release of HDM major allergens from the freeze-dried tablets was complete after 30 s, while only partial release was achieved with the compressed tablets, even after prolonged dissolution. At 1 min, i.e., the recommended sublingual holding time for the freeze-dried tablets, the allergen bioavailability (AUC) of the compressed 300 IR/57,000 JAU tablet was 4.7-fold (Der f 1), 10.8-fold (Der p 1), and 23.6-fold (Der 2) lower than that of the freeze-dried 12 SQ-HDM/20,000 JAU tablet and similar to (Der f 1) and 5.3-fold (Der p 1) and 12.5-fold (Der 2) lower than that of the freeze-dried 6 SQ-HDM/10,000 JAU tablet. SLIT tablet allergen bioavailability depends highly on the tablet formulation. Only the fast-dissolving freeze-dried tablets provide maximal delivery of soluble allergens and achieve allergen concentrations that reflect the nominal tablet strengths within the recommended sublingual holding time. © 2017 S. Karger AG, Basel.

Network-Cognizant Voltage Droop Control for Distribution Grids

DOE PAGES

Baker, Kyri; Bernstein, Andrey; Dall'Anese, Emiliano; ...

2017-08-07

Our paper examines distribution systems with a high integration of distributed energy resources (DERs) and addresses the design of local control methods for real-time voltage regulation. Particularly, the paper focuses on proportional control strategies where the active and reactive output-powers of DERs are adjusted in response to (and proportionally to) local changes in voltage levels. The design of the voltage-active power and voltage-reactive power characteristics leverages suitable linear approximation of the AC power-flow equations and is network-cognizant; that is, the coefficients of the controllers embed information on the location of the DERs and forecasted non-controllable loads/injections and, consequently, on themore » effect of DER power adjustments on the overall voltage profile. We pursued a robust approach to cope with uncertainty in the forecasted non-controllable loads/power injections. Stability of the proposed local controllers is analytically assessed and numerically corroborated.« less

Network-Cognizant Voltage Droop Control for Distribution Grids

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

Baker, Kyri; Bernstein, Andrey; Dall'Anese, Emiliano

Our paper examines distribution systems with a high integration of distributed energy resources (DERs) and addresses the design of local control methods for real-time voltage regulation. Particularly, the paper focuses on proportional control strategies where the active and reactive output-powers of DERs are adjusted in response to (and proportionally to) local changes in voltage levels. The design of the voltage-active power and voltage-reactive power characteristics leverages suitable linear approximation of the AC power-flow equations and is network-cognizant; that is, the coefficients of the controllers embed information on the location of the DERs and forecasted non-controllable loads/injections and, consequently, on themore » effect of DER power adjustments on the overall voltage profile. We pursued a robust approach to cope with uncertainty in the forecasted non-controllable loads/power injections. Stability of the proposed local controllers is analytically assessed and numerically corroborated.« less

Spectral asymmetry of atoms in the van der Waals potential of an optical nanofiber

NASA Astrophysics Data System (ADS)

Patterson, B. D.; Solano, P.; Julienne, P. S.; Orozco, L. A.; Rolston, S. L.

2018-03-01

We measure the modification of the transmission spectra of cold 87Rb atoms in the proximity of an optical nanofiber (ONF). Van der Waals interactions between the atoms an the ONF surface decrease the resonance frequency of atoms closer to the surface. An asymmetric spectra of the atoms holds information of their spatial distribution around the ONF. We use a far-detuned laser beam coupled to the ONF to thermally excite atoms at the ONF surface. We study the change of transmission spectrum of these atoms as a function of heating laser power. A semiclassical phenomenological model for the thermal excitation of atoms in the atom-surface van der Waals bound states is in good agreement with the measurements. This result suggests that van der Waals potentials could be used to trap and probe atoms at few nanometers from a dielectric surface, a key tool for hybrid photonic-atomic quantum systems.

Messen, Kalibrieren, Eichen in der Radiologie: Prinzipien und Praxis

NASA Astrophysics Data System (ADS)

Wagner, Siegfried R.

Nach einleitender Erläuterung der unterschiedlichen Meßbedingungen in der Strahlentherapie und im Strahlenschutz werden die metrologischen Probleme am Beispiel der Größenkategorie Äquivalentdosis diskutiert. Als spezielle Größen werden effektive Äquivalentdosis und Umgebungs-Äquivalentdosis eingeführt. Es wird gezeigt, wie richtiges Messen durch ein konsistentes System von Bauartanforderungen an Meßgeräte, durch Kalibrieren und durch Eichen gewährleistet werden kann. Die Bedeutung von Meßunsicherheiten und Fehlergrenzen wird erläutert und ihre Auswirkung auf die Interpretation von Meßergebnissen behandelt.Translated AbstractMeasurements, Calibration, Verification in Radiology: Principles and PracticeThe different measuring conditions in radiotherapy and in radiation protection are discussed in the introduction. Then, the metrological problems are discussed exemplarily with the dose equivalent as a category of quantity. Effective dose equivalent and ambient dose equivalent are introduced as special quantities. It is demonstrated, how correct measurements can be secured by a consistent system of instrument pattern requirements, by calibration and verification. The importance of uncertainties of measurements and of error limits is illustrated and their influence on the interpretation of the results of measurements is treated.

Translesion synthesis DNA polymerases promote error-free replication through the minor-groove DNA adduct 3-deaza-3-methyladenine.

PubMed

Yoon, Jung-Hoon; Roy Choudhury, Jayati; Park, Jeseong; Prakash, Satya; Prakash, Louise

2017-11-10

N3-Methyladenine (3-MeA) is formed in DNA by reaction with S -adenosylmethionine, the reactive methyl donor, and by reaction with alkylating agents. 3-MeA protrudes into the DNA minor groove and strongly blocks synthesis by replicative DNA polymerases (Pols). However, the mechanisms for replicating through this lesion in human cells remain unidentified. Here we analyzed the roles of translesion synthesis (TLS) Pols in the replication of 3-MeA-damaged DNA in human cells. Because 3-MeA has a short half-life in vitro , we used the stable 3-deaza analog, 3-deaza-3-methyladenine (3-dMeA), which blocks the DNA minor groove similarly to 3-MeA. We found that replication through the 3-dMeA adduct is mediated via three different pathways, dependent upon Polι/Polκ, Polθ, and Polζ. As inferred from biochemical studies, in the Polι/Polκ pathway, Polι inserts a nucleotide (nt) opposite 3-dMeA and Polκ extends synthesis from the inserted nt. In the Polθ pathway, Polθ carries out both the insertion and extension steps of TLS opposite 3-dMeA, and in the Polζ pathway, Polζ extends synthesis following nt insertion by an as yet unidentified Pol. Steady-state kinetic analyses indicated that Polι and Polθ insert the correct nt T opposite 3-dMeA with a much reduced catalytic efficiency and that both Pols exhibit a high propensity for inserting a wrong nt opposite this adduct. However, despite their low fidelity of synthesis opposite 3-dMeA, TLS opposite this lesion replicates DNA in a highly error-free manner in human cells. We discuss the implications of these observations for TLS mechanisms in human cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Costs and Operating Dynamics of Integrating Distributed Energy Resources in Commercial and Industrial Buildings with Electric Vehicle Charging

NASA Astrophysics Data System (ADS)

Flores, Robert Joseph

Growing concerns over greenhouse gas and pollutant emissions have increased the pressure to shift energy conversion paradigms from current forms to more sustainable methods, such as through the use of distributed energy resources (DER) at industrial and commercial buildings. This dissertation is concerned with the optimal design and dispatch of a DER system installed at an industrial or commercial building. An optimization model that accurately captures typical utility costs and the physical constraints of a combined cooling, heating, and power (CCHP) system is designed to size and operate a DER system at a building. The optimization model is then used with cooperative game theory to evaluate the financial performance of a CCHP investment. The CCHP model is then modified to include energy storage, solar powered generators, alternative fuel sources, carbon emission limits, and building interactions with public and fleet PEVs. Then, a separate plugin electric vehicle (PEV) refueling model is developed to determine the cost to operate a public Level 3 fast charging station. The CCHP design and dispatch results show the size of the building load and consistency of the thermal loads are critical to positive financial performance. While using the CCHP system to produce cooling can provide savings, heat production drives positive financial performance. When designing the DER system to reduce carbon emissions, the use of renewable fuels can allow for a gas turbine system with heat recovery to reduce carbon emissions for a large university by 67%. Further reductions require large photovoltaic installations coupled with energy storage or the ability to export electricity back to the grid if costs are to remain relatively low. When considering Level 3 fast charging equipment, demand charges at low PEV travel levels are sufficiently high to discourage adoption. Integration of the equipment can reduce demand charge costs only if the building maximum demand does not coincide with PEV refueling. Electric vehicle refueling does not typically affect DER design at low PEV travel levels, but can as electric vehicle travel increases. However, as PEV travel increases, the stochastic nature of PEV refueling disappears, and the optimization problem may become deterministic.

Entwicklung von umwelt- und naturschutzgerechten Verfahren der landwirtschaftlichen Landnutzung für das Biosphärenreservat Schorfheide-Chorin

NASA Astrophysics Data System (ADS)

Meyer-Aurich, Andreas

1999-11-01

Mit der vorliegenden Arbeit werden exemplarisch Chancen und Grenzen der Integration von Umwelt- und Naturschutz in Verfahren der ackerbaulichen Landnutzung aufgezeigt. Die Umsetzung von Zielen des Umwelt- und Naturschutzes in Verfahren der Landnutzung ist mit verschiedenen Schwierigkeiten verbunden. Diese liegen zum einen in der Konkretisierung der Ziele, um diese umsetzen zu können, zum anderen in vielfach unzulänglichem Wissen über den Zusammenhang zwischen unterschiedlichen Formen der Landnutzung und insbesondere den biotischen Naturschutzzielen. Zunächst wird die Problematik der Zielfestlegung und Konkretisierung erörtert. Das Umweltqualitätszielkonzept von Fürst et al. (1992) stellt einen Versuch dar, Ziele des Umwelt- und Naturschutzes zu konkretisieren. Dieses Konzept haben Heidt et al. (1997) auf einen Landschaftsausschnitt von ca. 6000 ha im Biosphärenreservat Schorfheide-Chorin im Nordosten Brandenburgs angewendet. Eine Auswahl der von Heidt et al. (1997) formulierten Umweltqualitätsziele bildet die Basis dieser Arbeit. Für die ausgewählten Umweltqualitätsziele wurden wesentliche Einflussfaktoren der Landnutzung identifiziert und ein Bewertungssystem entwickelt, mit dem die Auswirkungen von landwirtschaftlichen Anbauverfahren auf diese Umweltqualitätsziele abgebildet werden können. Die praktizierte Landnutzung von 20 Betrieben im Biosphärenreservat Schorfheide-Chorin wurde von 1994 bis 1997 hinsichtlich ihrer Auswirkungen auf die Umweltqualitätsziele analysiert. Die Analyse ergab ein sehr differenziertes Bild, das zum Teil Unterschiede in der Auswirkung auf die Umweltqualitätsziele für den Anbau einzelner Kulturen oder für bestimmte Betriebstypen zeigte. Es zeigte sich aber auch, dass es bei der Gestaltung des Anbaus einzelner Kulturarten große Unterschiede gab, die für Umweltqualitätsziele Bedeutung haben. Neben der Analyse der Landnutzung im Biosphärenreservat Schorfheide-Chorin wurde ein System entwickelt, mit dem die modellhafte Abbildung von Verfahren der Landnutzung möglich ist. Die Modellverfahren wurden in eine umfangreiche Datenbank eingebunden. Sie wurden mit Hilfe eines Fuzzy- Regelsystems hinsichtlich ihrer Auswirkungen auf die Umweltqualitätsziele bewertet. Die systematisch bewerteten Verfahren wurden in ein Betriebsmodell integriert, womit eine weitergehende Analyse der Zielbeziehungen und die Berechnung von Szenarien mit unterschiedlichen Rahmenbedingungen ermöglicht wurde. Die Analyse der Beziehung verschiedener Ziele zueinander (Zieldivergenz, Zielkonvergenz) zeigte, dass sich mit der Verfolgung vieler Umweltqualitätsziele auch positive Effekte für andere Umweltqualitätsziele ergaben. Teilweise konnte allerdings auch eine Zieldivergenz festgestellt werden, die auf mögliche Zielkonflikte hinweist. Bei der Analyse der Szenarienergebnisse zeigte sich, dass die vorgeschlagenen Veränderungen von Rahmenbedingungen vielfach eine Verschlechterung für verschiedene Umweltqualitätsziele mit sich bringen. Eine Ursache dafür liegt darin, dass bei der Definition der Szenarien die Bedeutung der Stilllegungen unterschätzt wurde. The objective of this research was to show the opportunities and limitations associated with integrating of environmental goals into agricultural land use management. For this purpose, the impact of agricultural land uses on six environmental quality goals was analysed for an approximately 16.000 ha study region within the biosphere reserve Schorfheide-Chorin in north-eastern Brandenburg (Germany). The environmental quality goals considered were protection of ground water, preservation of groundwater recharge, protection of the soil against wind and water erosion and preservation of animal species typical of the agricultural landscape, in particular partridge, amphibians and cranes. For each environmental quality goal, an evaluation framework is presented which enables an assessment of the impact of agricultural land uses on the environmental quality goals. The evaluation framework was applied to assess the impact of land uses of twenty farms in the study area from 1994 to 1997. It was demonstrated that the impact of agricultural land uses on the environmental quality of the region is very complex, and - although some crops did significantly impact certain aspects, one factor did not overwhelmingly contribute to the overall environmental quality. The evaluation framework was integrated further into a system of modelled cropping practices for optimisation calculations. For this purpose, a model framework was established based on a MS Access database. In the database, cropping practices for 17 crops are stored. Inputs and yields are adapted to the site-specific yield potential. In addition to the cropping practices, the model framework is comprised of an evaluation module and optimisation module. Hence, the impact of the cropping practices can be assessed for each site. This model framework provides the basis for optimisation calculations to forecast various land uses under different conditions. A step-wise integration of the environmental quality goals into the optimisation algorithm of a model farm allows for showing trade-offs between economic and ecological goals. The results of the trade-offs show that an improvement of ecological goal achievement is possible with little impact on the gross margin, as long as the improvement is less than 30% of the starting situation. If improvements greater than 30% are desired, very high losses of gross margin must be taken into consideration. Another result of the calculations shows that high achievements of environmental quality goals often correlate with the percentage of set-aside land within the total area.

In vitro transcription activities of Pol IV, Pol V and RDR2 reveal coupling of Pol IV and RDR2 for dsRNA synthesis in plant RNA silencing

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

Haag, Jeremy R.; Ream, Thomas S.; Marasco, Michelle

2012-12-14

In Arabidopsis, RNA-dependent DNA methylation and transcriptional silencing involves three nuclear RNA polymerases that are biochemically undefined: the presumptive DNA-dependent RNA polymerases, Pol IV and Pol V and the putative RNA-dependent RNA polymerase, RDR2. Here, we demonstrate their RNA polymerase activities in vitro. Unlike Pol II, Pols IV and V require an RNA primer, are insensitive to alpha-amanitin and differ in their ability to displace non-template DNA during transcription. Biogenesis of 24 nt small interfering RNAs (siRNAs) requires both Pol IV and RDR2, which physically associate in vivo. Pol IV does not require RDR2 for activity, but RDR2 is nonfunctionalmore » in the absence of associated Pol IV, suggesting that their coupling explains the channeling of Pol IV transcripts into double-stranded RNAs that are then diced into 24 nt siRNAs.« less

Differential action and differential expression of DNA polymerase I during Escherichia coli colony development.

PubMed Central

Shapiro, J A

1992-01-01

A mini-Tn10 insertion in the polA cistron (polA2099) was isolated in a search for mutations that affect patterned Mudlac replication in colonies. The polA2099 mutation had a dramatic effect on cell morphogenesis during the first few hours of microcolony development. Abnormal microcolonies containing filamentous cells were produced as a result of SOS induction. Despite gross abnormalities in early microcolonies, mature polA2099 colonies after 2 to 4 days were morphologically indistinguishable from Pol+ colonies, and 44-h polA2099 colonies displayed a cell size distribution very similar to that of Pol+ colonies. These results suggested the involvement of a protective factor produced during colony growth that compensated for the polA deficiency. The action of a diffusible substance that stimulates growth of polA2099 microcolonies was shown by spotting dilute polA2099 cultures next to established colonies. Differential transcription of polA during colony development was visualized by growing colonies containing polA-lacZ fusions on beta-galactosidase indicator agar. When polA-lacZ colonies were inoculated next to established colonies, a diffusible factor was seen to inhibit polA transcription during the earliest stages of colony development. These results show that a basic housekeeping function, DNA polymerase I, is subject to multicellular control by the changing conditions which the bacteria create as they proliferate on agar. Images PMID:1331025

Genetic Control of Replication through N1-methyladenine in Human Cells*

PubMed Central

Conde, Juan; Yoon, Jung-Hoon; Roy Choudhury, Jayati; Prakash, Louise; Prakash, Satya

2015-01-01

N1-methyl adenine (1-MeA) is formed in DNA by reaction with alkylating agents and naturally occurring methyl halides. The 1-MeA lesion impairs Watson-Crick base pairing and blocks normal DNA replication. Here we identify the translesion synthesis (TLS) DNA polymerases (Pols) required for replicating through 1-MeA in human cells and show that TLS through this lesion is mediated via three different pathways in which Pols ι and θ function in one pathway and Pols η and ζ, respectively, function in the other two pathways. Our biochemical studies indicate that in the Polι/Polθ pathway, Polι would carry out nucleotide insertion opposite 1-MeA from which Polθ would extend synthesis. In the Polη pathway, this Pol alone would function at both the nucleotide insertion and extension steps of TLS, and in the third pathway, Polζ would extend from the nucleotide inserted opposite 1-MeA by an as yet unidentified Pol. Whereas by pushing 1-MeA into the syn conformation and by forming Hoogsteen base pair with the T residue, Polι would carry out TLS opposite 1-MeA, the ability of Polη to replicate through 1-MeA suggests that despite its need for Watson-Crick hydrogen bonding, Polη can stabilize the adduct in its active site. Remarkably, even though Pols η and ι are quite error-prone at inserting nucleotides opposite 1-MeA, TLS opposite this lesion in human cells occurs in a highly error-free fashion. This suggests that the in vivo fidelity of TLS Pols is regulated by factors such as post-translational modifications, protein-protein interactions, and possibly others. PMID:26491020

Quality control mechanisms exclude incorrect polymerases from the eukaryotic replication fork

PubMed Central

Schauer, Grant D.; O’Donnell, Michael E.

2017-01-01

The eukaryotic genome is primarily replicated by two DNA polymerases, Pol ε and Pol δ, that function on the leading and lagging strands, respectively. Previous studies have established recruitment mechanisms whereby Cdc45-Mcm2-7-GINS (CMG) helicase binds Pol ε and tethers it to the leading strand, and PCNA (proliferating cell nuclear antigen) binds tightly to Pol δ and recruits it to the lagging strand. The current report identifies quality control mechanisms that exclude the improper polymerase from a particular strand. We find that the replication factor C (RFC) clamp loader specifically inhibits Pol ε on the lagging strand, and CMG protects Pol ε against RFC inhibition on the leading strand. Previous studies show that Pol δ is slow and distributive with CMG on the leading strand. However, Saccharomyces cerevisiae Pol δ–PCNA is a rapid and processive enzyme, suggesting that CMG may bind and alter Pol δ activity or position it on the lagging strand. Measurements of polymerase binding to CMG demonstrate Pol ε binds CMG with a Kd value of 12 nM, but Pol δ binding CMG is undetectable. Pol δ, like bacterial replicases, undergoes collision release upon completing replication, and we propose Pol δ–PCNA collides with the slower CMG, and in the absence of a stabilizing Pol δ–CMG interaction, the collision release process is triggered, ejecting Pol δ on the leading strand. Hence, by eviction of incorrect polymerases at the fork, the clamp machinery directs quality control on the lagging strand and CMG enforces quality control on the leading strand. PMID:28069954

PCNA mono-ubiquitination and activation of translesion DNA polymerases by DNA polymerase {alpha}.

PubMed

Suzuki, Motoshi; Niimi, Atsuko; Limsirichaikul, Siripan; Tomida, Shuta; Miao Huang, Qin; Izuta, Shunji; Usukura, Jiro; Itoh, Yasutomo; Hishida, Takashi; Akashi, Tomohiro; Nakagawa, Yoshiyuki; Kikuchi, Akihiko; Pavlov, Youri; Murate, Takashi; Takahashi, Takashi

2009-07-01

Translesion DNA synthesis (TLS) involves PCNA mono-ubiquitination and TLS DNA polymerases (pols). Recent evidence has shown that the mono-ubiquitination is induced not only by DNA damage but also by other factors that induce stalling of the DNA replication fork. We studied the effect of spontaneous DNA replication errors on PCNA mono-ubiquitination and TLS induction. In the pol1L868F strain, which expressed an error-prone pol alpha, PCNA was spontaneously mono-ubiquitinated. Pol alpha L868F had a rate-limiting step at the extension from mismatched primer termini. Electron microscopic observation showed the accumulation of a single-stranded region at the DNA replication fork in yeast cells. For pol alpha errors, pol zeta participated in a generation of +1 frameshifts. Furthermore, in the pol1L868F strain, UV-induced mutations were lower than in the wild-type and a pol delta mutant strain (pol3-5DV), and deletion of the RAD30 gene (pol eta) suppressed this defect. These data suggest that nucleotide misincorporation by pol alpha induces exposure of single-stranded DNA, PCNA mono-ubiquitination and activates TLS pols.

Hepatitis B Virus Polymerase Localizes to the Mitochondria, and Its Terminal Protein Domain Contains the Mitochondrial Targeting Signal.

PubMed

Unchwaniwala, Nuruddin; Sherer, Nathan M; Loeb, Daniel D

2016-10-01

To understand subcellular sites of hepatitis B virus (HBV) replication, we visualized core (Cp), polymerase (Pol), and pregenomic RNA (pgRNA) in infected cells. Interestingly, we found that the majority of Pol localized to the mitochondria in cells undergoing viral replication. The mitochondrial localization of Pol was independent of both the cell type and other viral components, indicating that Pol contains an intrinsic mitochondrial targeting signal (MTS). Neither Cp nor pgRNA localized to the mitochondria during active replication, suggesting a role other than DNA synthesis for Pol at the mitochondria. The Pol of duck hepatitis B virus (DHBV) also localized to the mitochondria. This result indicates that localization of Pol to mitochondria is likely a feature of all hepadnaviruses. To map the MTS within HBV Pol, we generated a series of Pol-green fluorescent protein (Pol-GFP) fusions and found that a stretch spanning amino acids (aa) 141 to 160 of Pol was sufficient to target GFP to the mitochondria. Surprisingly, deleting aa 141 to 160 in full-length Pol did not fully ablate Pol's mitochondrial localization, suggesting that additional sequences are involved in mitochondrial targeting. Only by deleting the N-terminal 160 amino acids in full-length Pol was mitochondrial localization ablated. Crucial residues for pgRNA packaging are contained within aa 141 to 160, indicating a multifunctional role of this region of Pol in the viral life cycle. Our studies show an unexpected Pol trafficking behavior that is uncoupled from its role in viral DNA synthesis. Chronic infection by HBV is a serious health concern. Existing therapies for chronically infected individuals are not curative, underscoring the need for a better understanding of the viral life cycle to develop better antiviral therapies. To date, the most thoroughly studied function of Pol is to package the pgRNA and reverse transcribe it to double-stranded DNA within capsids. This study provides evidence for mitochondrial localization of Pol and defines the MTS. Recent findings have implicated a non-reverse transcription role for Pol in evading host innate immune responses. Mitochondria play an important role in controlling cellular metabolism, apoptosis, and innate immunity. Pol may alter one or more of these host mitochondrial functions to gain a replicative advantage and persist in chronically infected individuals. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The translesion DNA polymerases Pol ζ and Rev1 are activated independently of PCNA ubiquitination upon UV radiation in mutants of DNA polymerase δ

PubMed Central

Ma, Emilie; Veaute, Xavier; Coïc, Eric

2017-01-01

Replicative DNA polymerases cannot insert efficiently nucleotides at sites of base lesions. This function is taken over by specialized translesion DNA synthesis (TLS) polymerases to allow DNA replication completion in the presence of DNA damage. In eukaryotes, Rad6- and Rad18-mediated PCNA ubiquitination at lysine 164 promotes recruitment of TLS polymerases, allowing cells to efficiently cope with DNA damage. However, several studies showed that TLS polymerases can be recruited also in the absence of PCNA ubiquitination. We hypothesized that the stability of the interactions between DNA polymerase δ (Pol δ) subunits and/or between Pol δ and PCNA at the primer/template junction is a crucial factor to determine the requirement of PCNA ubiquitination. To test this hypothesis, we used a structural mutant of Pol δ in which the interaction between Pol3 and Pol31 is inhibited. We found that in yeast, rad18Δ-associated UV hypersensitivity is suppressed by pol3-ct, a mutant allele of the POL3 gene that encodes the catalytic subunit of replicative Pol δ. pol3-ct suppressor effect was specifically dependent on the Rev1 and Pol ζ TLS polymerases. This result strongly suggests that TLS polymerases could rely much less on PCNA ubiquitination when Pol δ interaction with PCNA is partially compromised by mutations. In agreement with this model, we found that the pol3-FI allele suppressed rad18Δ-associated UV sensitivity as observed for pol3-ct. This POL3 allele carries mutations within a putative PCNA Interacting Peptide (PIP) motif. We then provided molecular and genetic evidence that this motif could contribute to Pol δ-PCNA interaction indirectly, although it is not a bona fide PIP. Overall, our results suggest that the primary role of PCNA ubiquitination is to allow TLS polymerases to outcompete Pol δ for PCNA access upon DNA damage. PMID:29281621

dNTP pool levels modulate mutator phenotypes of error-prone DNA polymerase ε variants.

PubMed

Williams, Lindsey N; Marjavaara, Lisette; Knowels, Gary M; Schultz, Eric M; Fox, Edward J; Chabes, Andrei; Herr, Alan J

2015-05-12

Mutator phenotypes create genetic diversity that fuels tumor evolution. DNA polymerase (Pol) ε mediates leading strand DNA replication. Proofreading defects in this enzyme drive a number of human malignancies. Here, using budding yeast, we show that mutator variants of Pol ε depend on damage uninducible (Dun)1, an S-phase checkpoint kinase that maintains dNTP levels during a normal cell cycle and up-regulates dNTP synthesis upon checkpoint activation. Deletion of DUN1 (dun1Δ) suppresses the mutator phenotype of pol2-4 (encoding Pol ε proofreading deficiency) and is synthetically lethal with pol2-M644G (encoding altered Pol ε base selectivity). Although pol2-4 cells cycle normally, pol2-M644G cells progress slowly through S-phase. The pol2-M644G cells tolerate deletions of mediator of the replication checkpoint (MRC) 1 (mrc1Δ) and radiation sensitive (Rad) 9 (rad9Δ), which encode mediators of checkpoint responses to replication stress and DNA damage, respectively. The pol2-M644G mutator phenotype is partially suppressed by mrc1Δ but not rad9Δ; neither deletion suppresses the pol2-4 mutator phenotype. Thus, checkpoint activation augments the Dun1 effect on replication fidelity but is not required for it. Deletions of genes encoding key Dun1 targets that negatively regulate dNTP synthesis, suppress the dun1Δ pol2-M644G synthetic lethality and restore the mutator phenotype of pol2-4 in dun1Δ cells. DUN1 pol2-M644G cells have constitutively high dNTP levels, consistent with checkpoint activation. In contrast, pol2-4 and POL2 cells have similar dNTP levels, which decline in the absence of Dun1 and rise in the absence of the negative regulators of dNTP synthesis. Thus, dNTP pool levels correlate with Pol ε mutator severity, suggesting that treatments targeting dNTP pools could modulate mutator phenotypes for therapy.

Bildbasierte Navigation eines mobilen Roboters mittels omnidirektionaler und schwenkbarer Kamera

NASA Astrophysics Data System (ADS)

Nierobisch, Thomas; Hoffmann, Frank; Krettek, Johannes; Bertram, Torsten

Dieser Beitrag präsentiert einen neuartigen Ansatz zur entkoppelten Regelung der Kamera-Blickrichtung und der Bewegung eines mobilen Roboters im Kontext der bildbasierten Navigation. Eine schwenkbare monokulare Kamera hält unabhängig von der Roboterbewegung die relevanten Merkmale für die Navigation im Sichtfeld. Die Entkopplung der Kamerablickrichtung von der eigentlichen Roboterbewegung wird durch die Projektion der Merkmale auf eine virtuelle Bildebene realisiert. In der virtuellen Bildebene hängt die Ausprägung der visuellen Merkmale für die bildbasierte Regelung nur von der Roboterposition ab und ist unabhängig gegenüber der tatsächlichen Blickrichtung der Kamera. Durch die Schwenkbarkeit der monokularen Kamera wird der Arbeitsbereich, über dem sich ein Referenzbild zur bildbasierten Regelung eignet, gegenüber einer statischen Kamera signifikant vergrößert. Dies ermöglicht die Navigation auch in texturarmen Umgebungen, die wenig verwertbare Textur- und Strukturmerkmale aufweisen.

Erfassung tribologischer Zusammenhänge und Erkenntnisse in einer Datenbank

NASA Astrophysics Data System (ADS)

Gold, Peter Werner; Jacobs, Georg; Loos, J.; Rombach, Volker; Kurutas, Savas; Fröde, Astrid

Die Datenbank enthält die tribologischen und stofflichen Daten, die innerhalb des Sonderforschungsbereichs 442 ermittelt wurden. Sie wird genutzt, um Informationen über die Eigenschaften von Schmierstoffen und Werkstoffverbunden, sowie über Prüfstände und Versuchsergebnisse zu erhalten. Diese Wissensbasis kann dazu beitragen, ökologisch verträgliche Tribosysteme mit Hilfe der Auswerte-Systeme (Module) auszulegen. Dabei handelt es sich um Berechnungswerkzeuge und Expertenwissen z. B. in Bezug auf die Auswahl von Schichtsystemen. Eine nähere Beschreibung der Auswerte-Systeme kann den folgenden Abschnitten entnommen werden.

A Role for MINIYO and QUATRE-QUART2 in the Assembly of RNA Polymerases II, IV, and V in Arabidopsis.

PubMed

Li, Yaoxi; Yuan, Yuxiang; Fang, Xiaofeng; Lu, Xiuli; Lian, Bi; Zhao, Gaozhan; Qi, Yijun

2018-02-01

RNA polymerases IV and V (Pol IV and Pol V) are required for the generation of noncoding RNAs in RNA-directed DNA methylation (RdDM). Their subunit compositions resemble that of Pol II. The mechanism and accessory factors involved in their assembly remain largely unknown. In this study, we identified mutant alleles of MINIYO ( IYO ), QUATRE-QUART2 ( QQT2 ), and NUCLEAR RNA POLYMERASE B11/D11/E11 ( NRPB/D/E11 ) that cause defects in RdDM in Arabidopsis thaliana We found that Pol IV-dependent small interfering RNAs and Pol V-dependent transcripts were greatly reduced in the mutants. NRPE1, the largest subunit of Pol V, failed to associate with other Pol V subunits in the iyo and qqt2 mutants, suggesting the involvement of IYO and QQT2 in Pol V assembly. In addition, we found that IYO and QQT2 were mutually dependent for their association with the NRPE3 subassembly prior to the assembly of Pol V holoenzyme. Finally, we show that IYO and QQT2 are similarly required for the assembly of Pol II and Pol IV. Our findings reveal IYO and QQT2 as cofactors for the assembly of Pol II, Pol IV, and Pol V and provide mechanistic insights into how RNA polymerases are assembled in plants. © 2018 American Society of Plant Biologists. All rights reserved.

Component-Resolved Diagnostic Study of Dermatophagoides Pteronyssinus Major Allergen Molecules in a Southern Chinese Cohort.

PubMed

Zeng, G; Luo, W; Zheng, P; Wei, N; Huang, H; Sun, B; Zhao, X

2015-01-01

Little is known about component-resolved diagnosis (CRD) for Dermatophagoides pteronyssinus (Der p) sensitization in the Chinese population. We aimed to evaluate sensitization to Der p components in southern China. Two-hundred immunotherapy-naïve patients with asthma and/or rhinitis positive to specific IgE (sIgE) against Der p extract, along with 20 Der p-negative nonallergic healthy controls, were tested for sIgE against Der p 1, Der p 2, and Der p 10 using ImmunoCAP 100. Seventy-five were further examined with the ImmunoCAP Immuno Solid-phase Allergen Chip (ISAC). Der p 10-positive patients were also tested for sIgE against crude extracts of cockroach, moth, and shrimp. In total, 183 (91.5%) of the 200 patients were sensitized to Der p 1 and/or Der p 2. The proportion of positive results and the median level of s1gE against Der p 1 were higher in children than in adults. Der p 1 and Der p 2 correlated with Der p in sIgE levels. ImmunoCAP ISAC demonstrated 100% specificity and 84% sensitivity in detecting Der p 1, Der p 2, and Der p 10 compared with ImmunoCAP 100. Sensitization to Der p 10 correlated well with sIgE to shrimp, moths, cockroaches, Pen m 1, Bla g 7, and Ani s 3. The detection of Der p 1 and Der p 2 provided a good reflection of atopy to Der p in a Chinese cohort. Sensitization to Der p 10 may result from cross-reactivity with seafood and cockroaches in coastal southern China. ImmunoCAP ISAC may be a useful tool for CRD, with comparable performance to ImmunoCAP 100.

Miocene climate as recorded on slope carbonates : examples from Malta (Central Mediterranean) and Northeastern Australia (Marion Plateau, ODP LEG 194)

NASA Astrophysics Data System (ADS)

John, Cédric Michaël

2003-08-01

This study investigated the slope carbonates of two Miocene carbonate systems: the Maltese Islands (in the Central Mediterranean) and the Marion Plateau (Northeastern Australia, drilled during ODP Leg 194). The aim of the study was to trace the impact of the Miocene cooling steps (events Mi1-Mi6) in these carbonate systems, especially the Mi3 event, which took place around 13.6 Ma and deeply impacted the marine oxygen isotope record. This event also profoundly impacted oceanographic and climatic patterns, eventually leading to the establishment of the modern ice-house world. In particular, East Antarctica became ice covered at that period. The rational behind the present study was to investigate the impact that this event had on shallow water systems in order to complement the deep-sea record and hence acquire a more global perspective on Miocene climate change. The Maltese Islands were investigated for trends in bulk-rock carbon and oxygen isotopes, as well as bulk-rock mineralogy, clay minerals analysis and organic geochemisty. Results showed that the mid Miocene cooling event deeply impacted sedimentation at that location by changing sedimentation from carbonate to clay-rich sediments. Moreover, it was discovered that each phase of Antarctic glaciation, not just the major mid Miocene event, resulted in higher terrigenous input on Malta. Mass accumulation rates revealed that this was linked to increased runoff during periods when Antarctica was glaciated, and thus that the carbonate sediments were “diluted” by clay-rich sediments. The model subsequently developed to explain this implies feedback from Antarctic glaciations creating cold, dense air masses that push the ITCZ Northward, thus increasing precipitation on the North African subcontinent. Increased precipitation (or stronger African monsoon) accelerated continental weathering and runoff, thus bringing more terrigenous sediment to the paleo-location of the slope sediments of Malta. Spectral analysis of carbonate content and organic matter geochemical analysis furthermore suggest that the clay-rich intervals are similar to sapropelic deposits. On the Marion Plateau, trends in oxygen and carbon isotopes were obtained by measuring Cibicidoides spp foraminifers. Moreover, carbonate content was reconstructed using a chemical method (coulometer). Results show that the mid Miocene cooling step profoundly affected this system: a major drop in accumulation rates of carbonates occurs precisely at 13.8 Ma, around the time of the East Antarctic ice sheet formation. Moreover, sedimentation changes occurred at that time, carbonate fragments coming from neritic environments becoming less abundant, planktonic foraminifer content increasing and quartz and reworked glauconite being deposited. Conversely, a surprising result is that the major N12-N14 sea-level fall occurring around 11.5 Ma did not impact the accumulation of carbonates on the slope. This was unexpected since carbonate platform are very sensitive to sea-level changes. The model developed to explain that mass accumulation rates of carbonates diminished around 13.6 Ma (Mi3 Event) instead of 11.5 Ma (N12-N14 event), suggests that oceanic currents were controlling slope carbonate deposition on the Marion Plateau prior to the mid-Miocene, and that the mid Miocene event considerably increase their strength, hence reducing the amount of carbonate being deposited on slope sites. Moreover, by combining results from deep-sea oxygen isotopes with sea-level estimates based on coastal onlaps made during Leg 194, we constrain the amplitude of the N12-N14 sea-level fall to 90 meters. When integrating isotopic results from this study, this amplitude is lowered to 70 meters. A general conclusion of this work is that the mid Miocene climatic shift did impact carbonate systems, at least at the two locations studied. However, the nature of this response was highly dependant on the regional settings, in particular the presence of land mass (Malta) and the absence of a barrier to shelter from the effects of open ocean (Marion Plateau). Im Rahmen dieser Doktorarbeit wurden die Hangkarbonate von zwei miozänen heterozoischen Karbonatsystemen näher untersucht: die Malta Inselgruppe (zentrales Mittelmeer) und das Marion Plateau (Nordost Australien, ODP Leg 194). Die Auswirkungen der mittelmiozänen Abkühlung (Mi3), die auf 13.6 Ma datiert wird und starken Einfluß auf die Sauerstoffisotopenkurve hatte, in den oben genannten Flachwassersystemen stellten das Ziel dieser Arbeit dar. Dieses Abkühlungsereignis beeinflußte außerdem sehr stark die ozeanographischen und klimatischen Muster, die im weiteren Verlauf zum modernen Eishausklima führten. So steht insbesondere die Vereisung von Ostantarktika mit diesem Ereignis in Verbindung. Diese Arbeit untersucht den Einfluß dieses Ereignisses auf Flachwassersysteme, um vorliegende Untersuchungen in Tiefwassersystemen zu ergänzen und so zum globalen Verständnis des miozänen Klimawechsels beizutragen. Die Profile auf der Maltainselgruppe wurden mit Hilfe von Kohlenstoff- und Sauerstoffisotopen Auswertungen im Gesamtgestein, Gesamtgesteinmineralogie, Tonmineralanalyse und organischer Geochemie untersucht. Durch einen Wechsel von karbonatischeren zu tonigeren Sedimenten beeinflußte das mittelmiozäne Abkühlungsereignis die Sedimentation in diesem Gebiet sehr stark. Weiterhin wurde beobachtet, daß jede Phase der antarktischen Vereisung, nicht nur das mittelmiozäne Hauptereignis, zu einem erhöhten terrigenen Eintrag in den Hangsedimenten der Maltainselgruppe führte. Akkumulationsraten zeigen, daß dieser erhöhte terrigene Eintrag den einzelnen Vereisungsperioden zusammenhängt und die karbonatischen Sedimente durch tonreiche Sedimente “verunreinigt” wurden. Das daraufhin entwickelte Modell erklärt diesen erhöhten terrigenen Eintrag mit einer nordwärtigen Verlagerung der innertropischen Konvergenzzone durch die Bildung von kalten, dichten Luftmassen, die zu verstärkten Niederschlägen in Nordafrika führten. Diese verstärkten Niederschläge (oder verstärkter afrikanischer Monsun) beeinflußten die kontinentale Verwitterung und den Eintrag, mit der Folge, daß verstärkt terrigene Sedimente im Bereich der Hangsedimente der Maltainselgruppe abgelagert wurden. Die tonreichen Intervalle weisen Ähnlichkeiten zu sapropelischen Ablagerungen auf, was mit Hilfe der Spektral analyse des Karbonatgehalts und der geochemischen Analyse des organischen Materials gezeigt wurde. Auf dem Marion Plateau wurden die Sauerstoff- und Kohlenstoffisotopenkurven anhand von Foraminiferen der Gattung Cibicidoides spp. rekonstruiert. Der Karbonatgehalt wurde mit Hilfe einer chemischen Methode (Coulometer) ermittelt. Genauso wie die Sedimente der Maltainselgruppe beeinflußte das mittelmiozäne Abkühlungsereignis (Mi3) auch die Sedimente auf dem Marion Plateau. So kam es bei 13,8 Ma, in etwa zur Zeit der Vereisung von Ostantarktika, zu einem Abfall der Karbonatakkumulationsraten. Weiterhin traten Änderungen in der Zusammensetzung der Sedimente auf, so nehmen neritische Karbonatfragmente ab, der planktische Foraminiferengehalt nimmt zu und es wurden verstärkt Quarz und Glaukonit abgelagert. Ein überraschendes Ergebnis ist die Tatsache, daß der große N12-N14 Meeresspiegelabfall um 11,5 Ma die Akkumulationsraten der Karbonate auf dem Hang nicht beeinflußte. Dieses Ergebnis ist umso erstaunlicher, da Karbonatplattformen normalerweise sehr sensitiv auf Meeresspiegeländerungen reagieren. Der Grund, warum sich die Karbonatakkumulationsraten schon um 13,6 Ma (Mi3) und nicht erst um 11,5 Ma (N12-N14) verringerten, liegt in der Tatsache, daß die ozeanischen Strömungen die Karbonatsedimentation auf dem Hang des Marion Plateau schon im Miozän kontrollierten. Das mittelmiozäne Ereignis (Mi3) erhöhte die Stärke diese Strömungen und als eine Ursache wurde die Karbonatakkumulation auf den Hängen reduziert. Die Amplitude des N12-N14 Meeresspiegelabfalls liegt bei 90 m unter der Berücksichtigung der Sauerstoffisotopendaten aus der Tiefsee und Berechnungen des Meeresspiegels anhand des “coastal onlaps”, die während Leg 194 gemacht wurden. Die Isotopendaten dieser Arbeit weisen hingegen auf einen verringerten Meeresspiegelabfall von 70 m hin. Als allgemeine Schlußfolgerung kann gesagt werden, daß der mittelmiozäne Klimaumschwung die Karbonatsysteme zumindest an den beiden untersuchten Lokalitäten beeinflußt hat. Allerdings waren die Auswirkungen sehr von den unterschiedlichen lokalen Gegebenheiten abhängig. Insbesondere wirkten sich die Anwesenheit einer Landmasse (Malta) und die Abwesenheit einer Barriere vor den Einflüssen des offenen Ozeans (Marion Plateau) stark auf die Ablagerung der Karbonate aus.

The Economics of van der Waals Force Engineering

NASA Astrophysics Data System (ADS)

Pinto, Fabrizio

2008-01-01

As micro-electro-mechanical system (MEMS) fabrication continues on an ever-decreasing scale, new technological challenges must be successfully negotiated if Moore's Law is to be an even approximately valid model of the future of device miniaturization. Among the most significant obstacles is the existence of strong surface forces related to quantum mechanical van der Waals interatomic interactions, which rapidly diverge as the distance between any two neutral boundaries decreases. The van der Waals force is a contributing factor in several device failures and limitations, including, for instance, stiction and oscillator non-linearities. In the last decade, however, it has been conclusively shown that van der Waals forces are not just a MEMS limitation but can be engineered in both magnitude and sign so as to enable classes of proprietary inventions which either deliver novel capabilities or improve upon existing ones. The evolution of van der Waals force research from an almost exclusively theoretical field in quantum-electro-dynamics to an enabling nanotechnology discipline represents a useful example of the ongoing paradigm shift from government-centered to private-capital funded R&D in cutting-edge physics leading to potentially profitable products. In this paper, we discuss the reasons van der Waals force engineering may lead to the creation of thriving markets both in the short and medium terms by highlighting technical challenges that can be competitively addressed by this novel approach. We also discuss some notable obstacles to the cultural transformation of the academic research community required for the emergence of a functional van der Waals force engineering industry worldwide.

Ubiquitin mediates the physical and functional interaction between human DNA polymerases η and ι

PubMed Central

McIntyre, Justyna; Vidal, Antonio E.; McLenigan, Mary P.; Bomar, Martha G.; Curti, Elena; McDonald, John P.; Plosky, Brian S.; Ohashi, Eiji; Woodgate, Roger

2013-01-01

Human DNA polymerases η and ι are best characterized for their ability to facilitate translesion DNA synthesis (TLS). Both polymerases (pols) co-localize in ‘replication factories’ in vivo after cells are exposed to ultraviolet light and this co-localization is mediated through a physical interaction between the two TLS pols. We have mapped the polη-ι interacting region to their respective ubiquitin-binding domains (UBZ in polη and UBM1 and UBM2 in polι), and demonstrate that ubiquitination of either TLS polymerase is a prerequisite for their physical and functional interaction. Importantly, while monoubiquitination of polη precludes its ability to interact with proliferating cell nuclear antigen (PCNA), it enhances its interaction with polι. Furthermore, a polι-ubiquitin chimera interacts avidly with both polη and PCNA. Thus, the ubiquitination status of polη, or polι plays a key regulatory function in controlling the protein partners with which each polymerase interacts, and in doing so, determines the efficiency of targeting the respective polymerase to stalled replication forks where they facilitate TLS. PMID:23248005

Role of damage-specific DNA polymerases in M13 phage mutagenesis induced by a major lipid peroxidation product trans-4-hydroxy-2-nonenal.

PubMed

Janowska, Beata; Kurpios-Piec, Dagmara; Prorok, Paulina; Szparecki, Grzegorz; Komisarski, Marek; Kowalczyk, Paweł; Janion, Celina; Tudek, Barbara

2012-01-03

One of the major lipid peroxidation products trans-4-hydroxy-2-nonenal (HNE), forms cyclic propano- or ethenoadducts bearing six- or seven-carbon atom side chains to G>C≫A>T. To specify the role of SOS DNA polymerases in HNE-induced mutations, we tested survival and mutation spectra in the lacZα gene of M13mp18 phage, whose DNA was treated in vitro with HNE, and which was grown in uvrA(-)Escherichia coli strains, carrying one, two or all three SOS DNA polymerases. When Pol IV was the only DNA SOS polymerase in the bacterial host, survival of HNE-treated M13 DNA was similar to, but mutation frequency was lower than in the strain containing all SOS DNA polymerases. When only Pol II or Pol V were present in host bacteria, phage survival decreased dramatically. Simultaneously, mutation frequency was substantially increased, but exclusively in the strain carrying only Pol V, suggesting that induction of mutations by HNE is mainly dependent on Pol V. To determine the role of Pol II and Pol IV in HNE induced mutagenesis, Pol II or Pol IV were expressed together with Pol V. This resulted in decrease of mutation frequency, suggesting that both enzymes can compete with Pol V, and bypass HNE-DNA adducts in an error-free manner. However, HNE-DNA adducts were easily bypassed by Pol IV and only infrequently by Pol II. Mutation spectrum established for strains expressing only Pol V, showed that in uvrA(-) bacteria the frequency of base substitutions and recombination increased in relation to NER proficient strains, particularly mutations at adenine sites. Among base substitutions A:T→C:G, A:T→G:C, G:C→A:T and G:C→T:A prevailed. The results suggest that Pol V can infrequently bypass HNE-DNA adducts inducing mutations at G, C and A sites, while bypass by Pol IV and Pol II is error-free, but for Pol II infrequent. Copyright © 2011 Elsevier B.V. All rights reserved.

Rosmarinic acid is a novel inhibitor for Hepatitis B virus replication targeting viral epsilon RNA-polymerase interaction.

PubMed

Tsukamoto, Yuta; Ikeda, Sotaro; Uwai, Koji; Taguchi, Riho; Chayama, Kazuaki; Sakaguchi, Takemasa; Narita, Ryo; Yao, Wan-Ling; Takeuchi, Fumihiko; Otakaki, Yukie; Watashi, Koichi; Wakita, Takaji; Kato, Hiroki; Fujita, Takashi

2018-01-01

Current therapeutics for hepatitis B virus (HBV) patients such as nucleoside analogs (NAs) are effective; however, new antiviral drugs against HBV are still desired. Since the interaction between the epsilon (ε) sequence of HBV pregenomic RNA and viral polymerase (Pol) is a key step in the HBV replication cycle, we aimed to identify small compounds for its inhibition, and established a pull-down assay system for the detection of ε-RNA-binding-Pol. Screening showed that 5 out of 3,965 compounds inhibited ε-Pol binding, and we identified rosmarinic acid, which exhibited specificity, as a potential antiviral agent. In order to examine the anti-HBV effects of rosmarinic acid, HBV-infected primary human hepatocytes from a humanized mouse liver were treated with rosmarinic acid. The rosmarinic acid treatment decreased HBV components including the amounts of extracellular HBV DNA with negligible cytotoxicity. We also investigated the combined effects of rosmarinic acid and the NA, lamivudine. rosmarinic acid slightly enhanced the anti-HBV activity of lamivudine, suggesting that the HBV replication step targeted by rosmarinic acid is distinct from that of NA. We analyzed an additional 25 rosmarinic acid derivatives, and found that 5 also inhibited ε-Pol. Structural comparisons between these derivatives implied that the "two phenolic hydroxyl groups at both ends" and the "caffeic acid-like structure" of rosmarinic acid are critical for the inhibition of ε-Pol binding. Collectively, our results demonstrate that rosmarinic acid inhibits HBV replication in HBV-infected cells by specifically targeting ε-Pol binding.

Das Smart Meter Gateway - Der kritische Erfolgsfaktor für die Digitalisierung der Energiewende

NASA Astrophysics Data System (ADS)

Abs, Paul-Vincent

Der kritische Erfolgsfaktor der Digitalisierung in der Energiewirtschaft liegt im bevorstehenden hohen Investitionsvolumen und der Beherrschung der neuen Technik. Ein Weg zur Kostenminimierung liegt im Zusammenschluss der einzelnen Akteure, um gemeinsame Skalenvorteile zu heben. Auch bieten neue Geschäftsmodelle die Möglichkeit, zusätzliche Erlöse zu generieren.

Inhibitory effect of tocotrienol on eukaryotic DNA polymerase {lambda} and angiogenesis

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

Mizushina, Yoshiyuki; Nakagawa, Kiyotaka; Shibata, Akira

2006-01-20

Tocotrienols, vitamin E compounds that have an unsaturated side chain with three double bonds, selectively inhibited the activity of mammalian DNA polymerase {lambda} (pol {lambda}) in vitro. These compounds did not influence the activities of replicative pols such as {alpha}, {delta}, and {epsilon}, or even the activity of pol {beta} which is thought to have a very similar three-dimensional structure to the pol {beta}-like region of pol {lambda}. Since {delta}-tocotrienol had the strongest inhibitory effect among the four ({alpha}- to {delta}-) tocotrienols, the isomer's structure might be an important factor in the inhibition of pol {lambda}. The inhibitory effect ofmore » {delta}-tocotrienol on both intact pol {lambda} (residues 1-575) and a truncated pol {lambda} lacking the N-terminal BRCA1 C-terminus (BRCT) domain (residues 133-575, del-1 pol {lambda}) was dose-dependent, with 50% inhibition observed at a concentration of 18.4 and 90.1 {mu}M, respectively. However, del-2 pol {lambda} (residues 245-575) containing the C-terminal pol {beta}-like region was unaffected. Tocotrienols also inhibited the proliferation of and formation of tubes by bovine aortic endothelial cells, with {delta}-tocotrienol having the greatest effect. These results indicated that tocotrienols targeted both pol {lambda} and angiogenesis as anti-cancer agents. The relationship between the inhibition of pol {lambda} and anti-angiogenesis by {delta}-tocotrienol was discussed.« less

Crosslinking-MS analysis reveals RNA polymerase I domain architecture and basis of rRNA cleavage

PubMed Central

Jennebach, Stefan; Herzog, Franz; Aebersold, Ruedi; Cramer, Patrick

2012-01-01

RNA polymerase (Pol) I contains a 10-subunit catalytic core that is related to the core of Pol II and includes subunit A12.2. In addition, Pol I contains the heterodimeric subcomplexes A14/43 and A49/34.5, which are related to the Pol II subcomplex Rpb4/7 and the Pol II initiation factor TFIIF, respectively. Here we used lysine-lysine crosslinking, mass spectrometry (MS) and modeling based on five crystal structures, to extend the previous homology model of the Pol I core, to confirm the location of A14/43 and to position A12.2 and A49/34.5 on the core. In the resulting model of Pol I, the C-terminal ribbon (C-ribbon) domain of A12.2 reaches the active site via the polymerase pore, like the C-ribbon of the Pol II cleavage factor TFIIS, explaining why the intrinsic RNA cleavage activity of Pol I is strong, in contrast to the weak cleavage activity of Pol II. The A49/34.5 dimerization module resides on the polymerase lobe, like TFIIF, whereas the A49 tWH domain resides above the cleft, resembling parts of TFIIE. This indicates that Pol I and also Pol III are distantly related to a Pol II–TFIIS–TFIIF–TFIIE complex. PMID:22396529

Mechanism of selective recruitment of RNA polymerases II and III to snRNA gene promoters.

PubMed

Dergai, Oleksandr; Cousin, Pascal; Gouge, Jerome; Satia, Karishma; Praz, Viviane; Kuhlman, Tracy; Lhôte, Philippe; Vannini, Alessandro; Hernandez, Nouria

2018-05-01

RNA polymerase II (Pol II) small nuclear RNA (snRNA) promoters and type 3 Pol III promoters have highly similar structures; both contain an interchangeable enhancer and "proximal sequence element" (PSE), which recruits the SNAP complex (SNAPc). The main distinguishing feature is the presence, in the type 3 promoters only, of a TATA box, which determines Pol III specificity. To understand the mechanism by which the absence or presence of a TATA box results in specific Pol recruitment, we examined how SNAPc and general transcription factors required for Pol II or Pol III transcription of SNAPc-dependent genes (i.e., TATA-box-binding protein [TBP], TFIIB, and TFIIA for Pol II transcription and TBP and BRF2 for Pol III transcription) assemble to ensure specific Pol recruitment. TFIIB and BRF2 could each, in a mutually exclusive fashion, be recruited to SNAPc. In contrast, TBP-TFIIB and TBP-BRF2 complexes were not recruited unless a TATA box was present, which allowed selective and efficient recruitment of the TBP-BRF2 complex. Thus, TBP both prevented BRF2 recruitment to Pol II promoters and enhanced BRF2 recruitment to Pol III promoters. On Pol II promoters, TBP recruitment was separate from TFIIB recruitment and enhanced by TFIIA. Our results provide a model for specific Pol recruitment at SNAPc-dependent promoters. © 2018 Dergai et al.; Published by Cold Spring Harbor Laboratory Press.

A reverse genetics system for enterovirus D68 using human RNA polymerase I.

PubMed

Pan, Minglei; Gao, Shuai; Zhou, Zhenwei; Zhang, Keke; Liu, Sihua; Wang, Zhiyun; Wang, Tao

2018-05-17

Human enterovirus D68 (EV-D68) is a highly contagious virus, which causes respiratory tract infections. However, no effective vaccines are currently available for controlling EV-D68 infection. Here, we developed a reverse genetics system to recover EV-D68 minireplicons and infectious EV-D68 from transfected plasmids using the RNA polymerase I (Pol I) promoter. The EV-D68 minireplicons contained the luciferase reporter gene, which flanked by the non-coding regions of the EV-D68 RNA. The luciferase signals could be detected in cells after transfection and Pol I promoter-mediated luciferase signal was significantly stronger than that mediated by the T7 promoter. Furthermore, recombinant viruses were generated by transfecting plasmids that contained the genomic RNA segments of EV-D68, under the control of Pol I promoter into 293T cells or RD cells. On plaque morphology and growth kinetics, the rescued virus and parental virus were indistinguishable. In addition, we showed that the G394C mutation disrupts the viral 5'-UTR structure and suppresses the viral cap-independent translation. This reverse genetics system for EV-D68 recovery can greatly facilitate research into EV-D68 biology. Moreover, this system could accelerate the development of EV-D68 vaccines and anti-EV-D68 drugs.

Replicative DNA polymerase mutations in cancer☆

PubMed Central

Heitzer, Ellen; Tomlinson, Ian

2014-01-01

Three DNA polymerases — Pol α, Pol δ and Pol ɛ — are essential for DNA replication. After initiation of DNA synthesis by Pol α, Pol δ or Pol ɛ take over on the lagging and leading strand respectively. Pol δ and Pol ɛ perform the bulk of replication with very high fidelity, which is ensured by Watson–Crick base pairing and 3′exonuclease (proofreading) activity. Yeast models have shown that mutations in the exonuclease domain of Pol δ and Pol ɛ homologues can cause a mutator phenotype. Recently, we identified germline exonuclease domain mutations (EDMs) in human POLD1 and POLE that predispose to ‘polymerase proofreading associated polyposis’ (PPAP), a disease characterised by multiple colorectal adenomas and carcinoma, with high penetrance and dominant inheritance. Moreover, somatic EDMs in POLE have also been found in sporadic colorectal and endometrial cancers. Tumors with EDMs are microsatellite stable and show an ‘ultramutator’ phenotype, with a dramatic increase in base substitutions. PMID:24583393

Advanced Inverter Functions and Communication Protocols for Distribution Management

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

Nagarajan, Adarsh; Palmintier, Bryan; Baggu, Murali

2016-05-05

This paper aims at identifying the advanced features required by distribution management systems (DMS) service providers to bring inverter-connected distributed energy resources into use as an intelligent grid resource. This work explores the standard functions needed in the future DMS for enterprise integration of distributed energy resources (DER). The important DMS functionalities such as DER management in aggregate groups, including the discovery of capabilities, status monitoring, and dispatch of real and reactive power are addressed in this paper. It is intended to provide the industry with a point of reference for DER integration with other utility applications and to providemore » guidance to research and standards development organizations.« less

Trichomonas vaginalis ribosomal RNA: identification and characterisation of the transcription promoter and terminator sequences.

PubMed

Franco, Bernardo; Hernández, Roberto; López-Villaseñor, Imelda

2012-09-01

Trichomonas vaginalis is a parasitic protozoan of both medical and biological relevance. Transcriptional studies in this organism have focused mainly on type II pol promoters, whereas the elements necessary for transcription by polI or polIII have not been investigated. Here, with the aid of a transient transcription system, we characterised the rDNA intergenic region, defining both the promoter and the terminator sequences required for transcription. We defined the promoter as a compact region of approximately 180 bp. We also identified a potential upstream control element (UCE) that was located 80 bp upstream of the transcription start point (TSP). A transcription termination element was identified within a 34 bp region that was located immediately downstream of the 28S coding sequence. The function of this element depends upon polarity and the presence of both a stretch of uridine residues (U's) and a hairpin structure in the transcript. Our observations provide a strong basis for the study of DNA recognition by the polI transcriptional machinery in this early divergent organism. Copyright © 2012 Elsevier B.V. All rights reserved.

Polarimetric Calibration and Assessment of GF-3 Images in Steppe

NASA Astrophysics Data System (ADS)

Chang, Y.; Yang, J.; Li, P.; Shi, L.; Zhao, L.

2018-04-01

The GaoFen-3 (GF-3) satellite is the first fully polarimetric synthetic aperture radar (PolSAR) satellite in China. It has three fully polarimetric imaging modes and is available for many applications. The system has been taken on several calibration experiments after the launch in Inner Mongolia by the Institute of Electronics, Chinese Academy of Sciences (IECAS), and the polarimetric calibration (PolCAL) strategy of GF-3 are also improved. Therefore, it is necessary to assess the image quality before any further applications. In this paper, we evaluated the polarimetric residual errors of GF-3 images that acquired in July 2017 in a steppe site. The results shows that the crosstalk of these images varies from -36 dB to -46 dB, and the channel imbalance varies from -0.43 dB to 0.55 dB with angle varying from -1.6 to 3.6 degree. We also made a PolCAL experiment to restrain the polarimetric distortion afterwards, and the polarimetric quality of the image got better after the PolCAL processing.

Homologous recombination mediates S-phase-dependent radioresistance in cells deficient in DNA polymerase eta.

PubMed

Nicolay, Nils H; Carter, Rebecca; Hatch, Stephanie B; Schultz, Niklas; Prevo, Remko; McKenna, W Gillies; Helleday, Thomas; Sharma, Ricky A

2012-11-01

DNA polymerase eta (pol η) is the only DNA polymerase causally linked to carcinogenesis in humans. Inherited deficiency of pol η in the variant form of xeroderma pigmentosum (XPV) predisposes to UV-light-induced skin cancer. Pol η-deficient cells demonstrate increased sensitivity to cisplatin and oxaliplatin chemotherapy. We have found that XP30R0 fibroblasts derived from a patient with XPV are more resistant to cell kill by ionising radiation (IR) than the same cells complemented with wild-type pol η. This phenomenon has been confirmed in Burkitt's lymphoma cells, which either expressed wild-type pol η or harboured a pol η deletion. Pol η deficiency was associated with accumulation of cells in S-phase, which persisted after IR. Cells deficient in pol η demonstrated increased homologous recombination (HR)-directed repair of double strand breaks created by IR. Depletion of the HR protein, X-ray repair cross-complementing protein 3 (XRCC3), abrogated the radioresistance observed in pol η-deficient cells as compared with pol η-complemented cells. These findings suggest that HR mediates S-phase-dependent radioresistance associated with pol η deficiency. We propose that pol η protein levels in tumours may potentially be used to identify patients who require treatment with chemo-radiotherapy rather than radiotherapy alone for adequate tumour control.

Strand displacement synthesis by yeast DNA polymerase ε

PubMed Central

Ganai, Rais A.; Zhang, Xiao-Ping; Heyer, Wolf-Dietrich; Johansson, Erik

2016-01-01

DNA polymerase ε (Pol ε) is a replicative DNA polymerase with an associated 3′–5′ exonuclease activity. Here, we explored the capacity of Pol ε to perform strand displacement synthesis, a process that influences many DNA transactions in vivo. We found that Pol ε is unable to carry out extended strand displacement synthesis unless its 3′–5′ exonuclease activity is removed. However, the wild-type Pol ε holoenzyme efficiently displaced one nucleotide when encountering double-stranded DNA after filling a gap or nicked DNA. A flap, mimicking a D-loop or a hairpin structure, on the 5′ end of the blocking primer inhibited Pol ε from synthesizing DNA up to the fork junction. This inhibition was observed for Pol ε but not with Pol δ, RB69 gp43 or Pol η. Neither was Pol ε able to extend a D-loop in reconstitution experiments. Finally, we show that the observed strand displacement synthesis by exonuclease-deficient Pol ε is distributive. Our results suggest that Pol ε is unable to extend the invading strand in D-loops during homologous recombination or to add more than two nucleotides during long-patch base excision repair. Our results support the hypothesis that Pol ε participates in short-patch base excision repair and ribonucleotide excision repair. PMID:27325747

Rückwärtsintegration - Zu den Verhältnissen Gymnasium, Hochschule und Arbeitswelt

NASA Astrophysics Data System (ADS)

Schmid, Gerhard; Heppner, Winfried; Focht, Eva

In seiner 2007 erschienen Sammlung von Vorträgen und Essays beschäftigt sich Wolfgang Frühwald, mit der Frage "Wieviel Wissen brauchen wir?“ [1] Die Kernproblematik moderner Wissenschaft und Forschung sieht der Autor, emeritierter Ordinarius für Neuere Deutsche Literaturwissenschaft und von 1992 bis 1997 Präsident der Deutschen Forschungsgemeinschaft, einerseits in der zunehmenden Spezialisierung der Wissenschaftsbereiche, andererseits in der Gefahr der Abkoppelung der Naturwissenschaften von den Geisteswissenschaften. Wiederholt plädiert er dafür, über der rasanten Entwicklung beispielsweise in der Biologie und Physik, die historische, gesellschaftliche und besonders die ethische Dimension der Forschung nicht zu übersehen und fordert eine übergeordnete Theorie der Wissenschaft, die nur im Dialog zwischen den einzelnen Fachgebieten zu entwickeln sei.

Both High-Fidelity Replicative and Low-Fidelity Y-Family Polymerases Are Involved in DNA Rereplication

PubMed Central

Sekimoto, Takayuki; Oda, Tsukasa; Kurashima, Kiminori; Hanaoka, Fumio

2014-01-01

DNA rereplication is a major form of aberrant replication that causes genomic instabilities, such as gene amplification. However, little is known about which DNA polymerases are involved in the process. Here, we report that low-fidelity Y-family polymerases (Y-Pols), Pol η, Pol ι, Pol κ, and REV1, significantly contribute to DNA synthesis during rereplication, while the replicative polymerases, Pol δ and Pol ε, play an important role in rereplication, as expected. When rereplication was induced by depletion of geminin, these polymerases were recruited to rereplication sites in human cell lines. This finding was supported by RNA interference (RNAi)-mediated knockdown of the polymerases, which suppressed rereplication induced by geminin depletion. Interestingly, epistatic analysis indicated that Y-Pols collaborate in a common pathway, independently of replicative polymerases. We also provide evidence for a catalytic role for Pol η and the involvement of Pol η and Pol κ in cyclin E-induced rereplication. Collectively, our findings indicate that, unlike normal S-phase replication, rereplication induced by geminin depletion and oncogene activation requires significant contributions of both Y-Pols and replicative polymerases. These findings offer important mechanistic insights into cancer genomic instability. PMID:25487575

Biochemical analysis of DNA polymerase η fidelity in the presence of replication protein A.

PubMed

Suarez, Samuel C; Toffton, Shannon M; McCulloch, Scott D

2014-01-01

DNA polymerase η (pol η) synthesizes across from damaged DNA templates in order to prevent deleterious consequences like replication fork collapse and double-strand breaks. This process, termed translesion synthesis (TLS), is an overall positive for the cell, as cells deficient in pol η display higher mutation rates. This outcome occurs despite the fact that the in vitro fidelity of bypass by pol η alone is moderate to low, depending on the lesion being copied. One possible means of increasing the fidelity of pol η is interaction with replication accessory proteins present at the replication fork. We have previously utilized a bacteriophage based screening system to measure the fidelity of bypass using purified proteins. Here we report on the fidelity effects of a single stranded binding protein, replication protein A (RPA), when copying the oxidative lesion 7,8-dihydro-8-oxo-guanine(8-oxoG) and the UV-induced cis-syn thymine-thymine cyclobutane pyrimidine dimer (T-T CPD). We observed no change in fidelity dependent on RPA when copying these damaged templates. This result is consistent in multiple position contexts. We previously identified single amino acid substitution mutants of pol η that have specific effects on fidelity when copying both damaged and undamaged templates. In order to confirm our results, we examined the Q38A and Y52E mutants in the same full-length construct. We again observed no difference when RPA was added to the bypass reaction, with the mutant forms of pol η displaying similar fidelity regardless of RPA status. We do, however, observe some slight effects when copying undamaged DNA, similar to those we have described previously. Our results indicate that RPA by itself does not affect pol η dependent lesion bypass fidelity when copying either 8-oxoG or T-T CPD lesions.

Grundlegende Steuerungsverfahren im heterogenen Logistiknetz mit Kanban

NASA Astrophysics Data System (ADS)

Dickmann, Eva; Dickmann, Philipp; Lödding, Hermann; Möller, Niklas; Rücker, Thomas; Schneider, Herfried M.; Zäh, Michael F.

In vielen Unternehmen werden heterogene (verschiedene) Steuerungen in einem abgestimmten Konzept kombiniert. Je nach Anwendungsfall und Rahmenbedingungen werden Kombinationen allgemein bekannter Steuerungen oder Steuerungsvarianten gemischt eingesetzt, um eine optimale Steuerung für unterschiedliche Fälle zu erreichen. Hierbei stehen neben den bekannten und weit verbreiteten Methoden, wie Material Requirements Planning (MRP) oder Kanban, auch weniger bekannte oder neue Methoden zur Auswahl, wie die Produktionssteuerung mit dezentraler, bestandsorientierter Fertigungsregelung (DBF). Kanban ist ein simples und effizientes Steuerungskonzept, das in der klassischen Form für spezifische einfache Anwendungsfälle umsetzbar ist. Hochentwickelte Steuerungsalgorithmen können helfen, komplexe Abläufe optimal abzubilden. Mit einer grundlegenden Vereinfachung der Abläufe kann allerdings in vielen Fällen ein wesentlich stärkerer und umfassender Verbesserungseffekt erzielt werden. Die wesentliche Fragestellung sollte folglich lauten: Warum ist der Ablauf nicht mit einer einfachen Steuerung wie Kanban abzubilden? Um die Vorteile des Konzepts auch in untypischen Bereichen anwenden zu können, sind jedoch verschiedene Varianten oder Kanban-ähnliche Steuerungsmethoden entstanden. Darüber hinaus sind in der Praxis hybride Steuerungen im Einsatz, welche so kombiniert werden, dass die Zusammensetzung anspruchsvolle Eigenschaftsbilder noch exakt abbildet. In der Praxis basieren die Steuerungsentscheidungen nur zu einem kleinen Teil auf den eigentlichen Steuerungsalgorithmen, wie sie uns das MRP-System zur Verfügung stellt. Moderne Steuerungswelten" schließen alle relevanten Informationsquellen in eine heterogene Entscheidungsmatrix mit ein. Letztlich zählt nicht, ob die Entscheidung auf den Informationen aus dem MRP-System oder auf Softfacts basierend getroffen wurde, sondern nur, ob die Entscheidung erfolgreich war.

Architecture of the Yeast RNA Polymerase II Open Complex and Regulation of Activity by TFIIF

PubMed Central

Fishburn, James

2012-01-01

To investigate the function and architecture of the open complex state of RNA polymerase II (Pol II), Saccharomyces cerevisiae minimal open complexes were assembled by using a series of heteroduplex HIS4 promoters, TATA binding protein (TBP), TFIIB, and Pol II. The yeast system demonstrates great flexibility in the position of active open complexes, spanning 30 to 80 bp downstream from TATA, consistent with the transcription start site scanning behavior of yeast Pol II. TFIIF unexpectedly modulates the activity of the open complexes, either repressing or stimulating initiation. The response to TFIIF was dependent on the sequence of the template strand within the single-stranded bubble. Mutations in the TFIIB reader and linker region, which were inactive on duplex DNA, were suppressed by the heteroduplex templates, showing that a major function of the TFIIB reader and linker is in the initiation or stabilization of single-stranded DNA. Probing of the architecture of the minimal open complexes with TFIIB-FeBABE [TFIIB–p-bromoacetamidobenzyl–EDTA-iron(III)] derivatives showed that the TFIIB core domain is surprisingly positioned away from Pol II, and the addition of TFIIF repositions the TFIIB core domain to the Pol II wall domain. Together, our results show an unexpected architecture of minimal open complexes and the regulation of activity by TFIIF and the TFIIB core domain. PMID:22025674

Roles of Rev1, Pol ζ, Pol32 and Pol η in the bypass of chromosomal abasic sites in Saccharomyces cerevisiae

PubMed Central

Auerbach, Paul A.; Demple, Bruce

2010-01-01

Translesion synthesis (TLS) on DNA is a process by which potentially cytotoxic replication-blocking lesions are bypassed, but at the risk of increased mutagenesis. The exact in vivo role of the individual TLS enzymes in Saccharomyces cerevisiae has been difficult to determine from previous studies due to differing results from the variety of systems used. We have generated a series of S.cerevisiae strains in which each of the TLS-related genes REV1, REV3, REV7, RAD30 and POL32 was deleted, and in which chromosomal apyrimidinic sites were generated during normal cell growth by the activity of altered forms of human uracil-DNA glycosylase that remove undamaged cytosines or thymines. Deletion of REV1, REV3 or REV7 resulted in slower growth dependent on (rev3Δ and rev7Δ) or enhanced by (rev1Δ) expression of the mutator glycosylases and a nearly complete abolition of glycosylase-induced mutagenesis. Deletion of POL32 resulted in cell death when the mutator glycosylases were expressed and, in their absence, diminished spontaneous mutagenesis. RAD30 appeared to be unnecessary for mutagenesis in response to abasic sites, as deleting this gene caused no significant change in either the mutation rates or the mutational spectra due to glycosylase expression. PMID:19901007

The Militarily Useful Clean Product Tanker: Sealift Component of the DoD Petroleum Distribution System.

DTIC Science & Technology

1983-12-01

dentlfIr by block numbher) Clean product tanker Defense Fuel Supply Center (DFSC) Handy Size Tanker (HST) Petroleum, Lubricants, and Oils (POL) Military...ccnsumer representing approximately 81 percent of tha " total. The majority of DOD energy is in the form of petro- leum, oil and lubricants (POL) with...annual consumption equating to 250 million barrels of oil . it h over five percent of *he DOD budget devoted to energy expnadiu::es, it is reasonable to

Interactions and Localization of Escherichia coli Error-Prone DNA Polymerase IV after DNA Damage.

PubMed

Mallik, Sarita; Popodi, Ellen M; Hanson, Andrew J; Foster, Patricia L

2015-09-01

Escherichia coli's DNA polymerase IV (Pol IV/DinB), a member of the Y family of error-prone polymerases, is induced during the SOS response to DNA damage and is responsible for translesion bypass and adaptive (stress-induced) mutation. In this study, the localization of Pol IV after DNA damage was followed using fluorescent fusions. After exposure of E. coli to DNA-damaging agents, fluorescently tagged Pol IV localized to the nucleoid as foci. Stepwise photobleaching indicated ∼60% of the foci consisted of three Pol IV molecules, while ∼40% consisted of six Pol IV molecules. Fluorescently tagged Rep, a replication accessory DNA helicase, was recruited to the Pol IV foci after DNA damage, suggesting that the in vitro interaction between Rep and Pol IV reported previously also occurs in vivo. Fluorescently tagged RecA also formed foci after DNA damage, and Pol IV localized to them. To investigate if Pol IV localizes to double-strand breaks (DSBs), an I-SceI endonuclease-mediated DSB was introduced close to a fluorescently labeled LacO array on the chromosome. After DSB induction, Pol IV localized to the DSB site in ∼70% of SOS-induced cells. RecA also formed foci at the DSB sites, and Pol IV localized to the RecA foci. These results suggest that Pol IV interacts with RecA in vivo and is recruited to sites of DSBs to aid in the restoration of DNA replication. DNA polymerase IV (Pol IV/DinB) is an error-prone DNA polymerase capable of bypassing DNA lesions and aiding in the restart of stalled replication forks. In this work, we demonstrate in vivo localization of fluorescently tagged Pol IV to the nucleoid after DNA damage and to DNA double-strand breaks. We show colocalization of Pol IV with two proteins: Rep DNA helicase, which participates in replication, and RecA, which catalyzes recombinational repair of stalled replication forks. Time course experiments suggest that Pol IV recruits Rep and that RecA recruits Pol IV. These findings provide in vivo evidence that Pol IV aids in maintaining genomic stability not only by bypassing DNA lesions but also by participating in the restoration of stalled replication forks. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Europeanization of the Hospital Markets - Opportunities and Risks for German Hospitals (Europaeisierung des Krankenhausmarkets - Chancen und Risiken fuer deutsche Krankenhaeuser)

DTIC Science & Technology

2004-07-06

Information Services Institut (3M HIS Institut) hat u.a. mit der Entwicklung eines Werkzeugs zur Pflege und Weiterentwicklung des deutschen DRG-Systems ftir... Pflege (Krankenhauspflege) a. die Kosten wachsen schneller als allgerneine Inflation b. praktisch stabile Krankenversicherungsentnahme c. es existieren 9...Krankenkassen d. die Pflege ist von der Krankenversicherung voll (theoretisch) vergUltet e. Missverhlitnis zwischen Versicherungsentnuhrne und

CHONDRICHTHYES, Knorpelfische

NASA Astrophysics Data System (ADS)

Goldschmid, Alfred

Die über 1.100 Arten der Knorpelfische sind nur etwa 4% aller heute lebenden Fischarten. Ihrknorpeliges Endoskelett kann zwar verkalken, wird abernie zu Knochen umgebaut. Der Schädel besteht nur aus Neurocranium und Viscerocranium, ein Dermatocranium fehlt. Knochen findet sich nur in den Plakoidschuppen der Körperdecke. Eine Schwimmblase wie bei den Knochenfischen wird nie gebildet. Mund- und Nasenöffnungen liegen ventral; der Endolymphgang bleibt zeitlebens mit der Epidermis verbunden. Der mediale Teil der Beckenflosse der Männchen dient als Kopulationsorgan (Mixopterygium, Klasper) (Abb. 208, 209B) bei der inneren Befruchtung.

Regulation of oxidative DNA damage repair by DNA polymerase λ and MutYH by cross-talk of phosphorylation and ubiquitination

PubMed Central

Markkanen, Enni; van Loon, Barbara; Ferrari, Elena; Parsons, Jason L.; Dianov, Grigory L.; Hübscher, Ulrich

2012-01-01

It is of pivotal importance for genome stability that repair DNA polymerases (Pols), such as Pols λ and β, which all exhibit considerably reduced fidelity when replicating undamaged DNA, are tightly regulated, because their misregulation could lead to mutagenesis. Recently, we found that the correct repair of the abundant and highly miscoding oxidative DNA lesion 7,8-dihydro-8-oxo-2′-deoxyguanine (8-oxo-G) is performed by an accurate repair pathway that is coordinated by the MutY glycosylase homologue (MutYH) and Pol λ in vitro and in vivo. Pol λ is phosphorylated by Cdk2/cyclinA in late S and G2 phases of the cell cycle, promoting Pol λ stability by preventing it from being targeted for proteasomal degradation by ubiquitination. However, it has remained a mystery how the levels of Pol λ are controlled, how phosphorylation promotes its stability, and how the engagement of Pol λ in active repair complexes is coordinated. Here, we show that the E3 ligase Mule mediates the degradation of Pol λ and that the control of Pol λ levels by Mule has functional consequences for the ability of mammalian cells to deal with 8-oxo-G lesions. Furthermore, we demonstrate that phosphorylation of Pol λ by Cdk2/cyclinA counteracts its Mule-mediated degradation by promoting recruitment of Pol λ to chromatin into active 8-oxo-G repair complexes through an increase in Pol λ’s affinity to chromatin-bound MutYH. Finally, MutYH appears to promote the stability of Pol λ by binding it to chromatin. In contrast, Pol λ not engaged in active repair on chromatin is subject for proteasomal degradation. PMID:22203964

Structural relationship of curcumin derivatives binding to the BRCT domain of human DNA polymerase lambda.

PubMed

Takeuchi, Toshifumi; Ishidoh, Tomomi; Iijima, Hiroshi; Kuriyama, Isoko; Shimazaki, Noriko; Koiwai, Osamu; Kuramochi, Kouji; Kobayashi, Susumu; Sugawara, Fumio; Sakaguchi, Kengo; Yoshida, Hiromi; Mizushina, Yoshiyuki

2006-03-01

We previously reported that phenolic compounds, petasiphenol and curcumin (diferuloylmethane), were a selective inhibitor of DNA polymerase lambda (pol lambda) in vitro. The purpose of this study was to investigate the molecular structural relationship of curcumin and 13 chemically synthesized derivatives of curcumin. The inhibitory effect on pol lambda (full-length, i.e. intact pol lambda including the BRCA1 C- terminal [BRCT] domain) by some derivatives was stronger than that by curcumin, and monoacetylcurcumin (compound 13) was the strongest pol lambda inhibitor of all the compounds tested, achieving 50% inhibition at a concentration of 3.9 microm. The compound did not influence the activities of replicative pols such as alpha, delta, and epsilon. It had no effect on pol beta activity either, although the three-dimensional structure of pol beta is thought to be highly similar to that of pol lambda. Compound 13 did not inhibit the activity of the C-terminal catalytic domain of pol lambda including the pol beta-like core, in which the BRCT motif was deleted from its N-terminal region. MALDI-TOF MS analysis demonstrated that compound 13 bound selectively to the N-terminal domain of pol lambda, but did not bind to the C-terminal region. Based on these results, the pol lambda-inhibitory mechanism of compound 13 is discussed.

Homologous recombination mediates S-phase-dependent radioresistance in cells deficient in DNA polymerase eta

PubMed Central

Sharma, Ricky A.

2012-01-01

DNA polymerase eta (pol η) is the only DNA polymerase causally linked to carcinogenesis in humans. Inherited deficiency of pol η in the variant form of xeroderma pigmentosum (XPV) predisposes to UV-light-induced skin cancer. Pol η-deficient cells demonstrate increased sensitivity to cisplatin and oxaliplatin chemotherapy. We have found that XP30R0 fibroblasts derived from a patient with XPV are more resistant to cell kill by ionising radiation (IR) than the same cells complemented with wild-type pol η. This phenomenon has been confirmed in Burkitt’s lymphoma cells, which either expressed wild-type pol η or harboured a pol η deletion. Pol η deficiency was associated with accumulation of cells in S-phase, which persisted after IR. Cells deficient in pol η demonstrated increased homologous recombination (HR)-directed repair of double strand breaks created by IR. Depletion of the HR protein, X-ray repair cross-complementing protein 3 (XRCC3), abrogated the radioresistance observed in pol η-deficient cells as compared with pol η-complemented cells. These findings suggest that HR mediates S-phase-dependent radioresistance associated with pol η deficiency. We propose that pol η protein levels in tumours may potentially be used to identify patients who require treatment with chemo-radiotherapy rather than radiotherapy alone for adequate tumour control. PMID:22822095

Strand displacement synthesis by yeast DNA polymerase ε.

PubMed

Ganai, Rais A; Zhang, Xiao-Ping; Heyer, Wolf-Dietrich; Johansson, Erik

2016-09-30

DNA polymerase ε (Pol ε) is a replicative DNA polymerase with an associated 3'-5' exonuclease activity. Here, we explored the capacity of Pol ε to perform strand displacement synthesis, a process that influences many DNA transactions in vivo We found that Pol ε is unable to carry out extended strand displacement synthesis unless its 3'-5' exonuclease activity is removed. However, the wild-type Pol ε holoenzyme efficiently displaced one nucleotide when encountering double-stranded DNA after filling a gap or nicked DNA. A flap, mimicking a D-loop or a hairpin structure, on the 5' end of the blocking primer inhibited Pol ε from synthesizing DNA up to the fork junction. This inhibition was observed for Pol ε but not with Pol δ, RB69 gp43 or Pol η. Neither was Pol ε able to extend a D-loop in reconstitution experiments. Finally, we show that the observed strand displacement synthesis by exonuclease-deficient Pol ε is distributive. Our results suggest that Pol ε is unable to extend the invading strand in D-loops during homologous recombination or to add more than two nucleotides during long-patch base excision repair. Our results support the hypothesis that Pol ε participates in short-patch base excision repair and ribonucleotide excision repair. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Redundancy of mammalian Y family DNA polymerases in cellular responses to genomic DNA lesions induced by ultraviolet light

PubMed Central

Jansen, Jacob G.; Temviriyanukul, Piya; Wit, Niek; Delbos, Frédéric; Reynaud, Claude-Agnès; Jacobs, Heinz; de Wind, Niels

2014-01-01

Short-wave ultraviolet light induces both mildly helix-distorting cyclobutane pyrimidine dimers (CPDs) and severely distorting (6–4) pyrimidine pyrimidone photoproducts ((6–4)PPs). The only DNA polymerase (Pol) that is known to replicate efficiently across CPDs is Polη, a member of the Y family of translesion synthesis (TLS) DNA polymerases. Phenotypes of Polη deficiency are transient, suggesting redundancy with other DNA damage tolerance pathways. Here we performed a comprehensive analysis of the temporal requirements of Y-family Pols ι and κ as backups for Polη in (i) bypassing genomic CPD and (6–4)PP lesions in vivo, (ii) suppressing DNA damage signaling, (iii) maintaining cell cycle progression and (iv) promoting cell survival, by using mouse embryonic fibroblast lines with single and combined disruptions in these Pols. The contribution of Polι is restricted to TLS at a subset of the photolesions. Polκ plays a dominant role in rescuing stalled replication forks in Polη-deficient mouse embryonic fibroblasts, both at CPDs and (6–4)PPs. This dampens DNA damage signaling and cell cycle arrest, and results in increased survival. The role of relatively error-prone Pols ι and κ as backups for Polη contributes to the understanding of the mutator phenotype of xeroderma pigmentosum variant, a syndrome caused by Polη defects. PMID:25170086

An epitope-specific DerG-PG70 LEAPS vaccine modulates T cell responses and suppresses arthritis progression in two related murine models of rheumatoid arthritis.

PubMed

Mikecz, Katalin; Glant, Tibor T; Markovics, Adrienn; Rosenthal, Kenneth S; Kurko, Julia; Carambula, Roy E; Cress, Steve; Steiner, Harold L; Zimmerman, Daniel H

2017-07-13

Rheumatoid arthritis (RA) is an autoimmune joint disease maintained by aberrant immune responses involving CD4+ T helper (Th)1 and Th17 cells. In this study, we tested the therapeutic efficacy of Ligand Epitope Antigen Presentation System (LEAPS™) vaccines in two Th1 cell-driven mouse models of RA, cartilage proteoglycan (PG)-induced arthritis (PGIA) and PG G1-domain-induced arthritis (GIA). The immunodominant PG peptide PG70 was attached to a DerG or J immune cell binding peptide, and the DerG-PG70 and J-PG70 LEAPS vaccines were administered to the mice after the onset of PGIA or GIA symptoms. As indicated by significant decreases in visual and histopathological scores of arthritis, the DerG-PG70 vaccine inhibited disease progression in both PGIA and GIA, while the J-PG70 vaccine was ineffective. Splenic CD4+ cells from DerG-PG70-treated mice were diminished in Th1 and Th17 populations but enriched in Th2 and regulatory T (Treg) cells. In vitro spleen cell-secreted and serum cytokines from DerG-PG70-treated mice demonstrated a shift from a pro-inflammatory to an anti-inflammatory/regulatory profile. DerG-PG70 peptide tetramers preferentially bound to CD4+ T-cells of GIA spleen cells. We conclude that the DerG-PG70 vaccine (now designated CEL-4000) exerts its therapeutic effect by interacting with CD4+ cells, which results in an antigen-specific down-modulation of pathogenic T-cell responses in both the PGIA and GIA models of RA. Future studies will need to determine the potential of LEAPS vaccination to provide disease suppression in patients with RA. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Van der Waals interactions and the limits of isolated atom models at interfaces

PubMed Central

Kawai, Shigeki; Foster, Adam S.; Björkman, Torbjörn; Nowakowska, Sylwia; Björk, Jonas; Canova, Filippo Federici; Gade, Lutz H.; Jung, Thomas A.; Meyer, Ernst

2016-01-01

Van der Waals forces are among the weakest, yet most decisive interactions governing condensation and aggregation processes and the phase behaviour of atomic and molecular matter. Understanding the resulting structural motifs and patterns has become increasingly important in studies of the nanoscale regime. Here we measure the paradigmatic van der Waals interactions represented by the noble gas atom pairs Ar–Xe, Kr–Xe and Xe–Xe with a Xe-functionalized tip of an atomic force microscope at low temperature. Individual rare gas atoms were fixed at node sites of a surface-confined two-dimensional metal–organic framework. We found that the magnitude of the measured force increased with the atomic radius, yet detailed simulation by density functional theory revealed that the adsorption induced charge redistribution strengthened the van der Waals forces by a factor of up to two, thus demonstrating the limits of a purely atomic description of the interaction in these representative systems. PMID:27174162

Inter-layer and intra-layer heat transfer in bilayer/monolayer graphene van der Waals heterostructure: Is there a Kapitza resistance analogous?

NASA Astrophysics Data System (ADS)

Rajabpour, Ali; Fan, Zheyong; Vaez Allaei, S. Mehdi

2018-06-01

Van der Waals heterostructures have exhibited interesting physical properties. In this paper, heat transfer in hybrid coplanar bilayer/monolayer (BL-ML) graphene, as a model layered van der Waals heterostructure, was studied using non-equilibrium molecular dynamics (MD) simulations. The temperature profile and inter- and intra-layer heat fluxes of the BL-ML graphene indicated that, there is no fully developed thermal equilibrium between layers and the drop in the average temperature profile at the step-like BL-ML interface is not attributable to the effect of Kapitza resistance. By increasing the length of the system up to 1 μm in the studied MD simulations, the thermally non-equilibrium region was reduced to a small area near the step-like interface. All MD results were compared to a continuum model and a good match was observed between the two approaches. Our results provide a useful understanding of heat transfer in nano- and micro-scale layered materials and van der Waals heterostructures.

Layer-dependent band alignment of few layers of blue phosphorus and their van der Waals heterostructures with graphene

NASA Astrophysics Data System (ADS)

Pontes, Renato B.; Miwa, Roberto H.; da Silva, Antônio J. R.; Fazzio, Adalberto; Padilha, José E.

2018-06-01

The structural and electronic properties of few layers of blue phosphorus and their van der Waals heterostructures with graphene were investigated by means of first-principles electronic structure calculations. We study the four energetically most stable stacking configurations for multilayers of blue phosphorus. For all of them, the indirect band-gap semiconductor character, are preserved. We show that the properties of monolayer graphene and single-layer (bilayer) blue phosphorus are preserved in the van der Waals heterostructures. Further, our results reveal that under a perpendicular applied electric field, the position of the band structure of blue phosphorus with respect to that of graphene is tunable, enabling the effective control of the Schottky barrier height. Indeed, for the bilayer blue phosphorene on top of graphene, it is possible to even move the system into an Ohmic contact and induce a doping level of the blue phosphorene. All of these features are fundamental for the design of new nanodevices based on van der Waals heterostructures.

Molecular architecture of the human Mediator-RNA polymerase II-TFIIF assembly.

PubMed

Bernecky, Carrie; Grob, Patricia; Ebmeier, Christopher C; Nogales, Eva; Taatjes, Dylan J

2011-03-01

The macromolecular assembly required to initiate transcription of protein-coding genes, known as the Pre-Initiation Complex (PIC), consists of multiple protein complexes and is approximately 3.5 MDa in size. At the heart of this assembly is the Mediator complex, which helps regulate PIC activity and interacts with the RNA polymerase II (pol II) enzyme. The structure of the human Mediator-pol II interface is not well-characterized, whereas attempts to structurally define the Mediator-pol II interaction in yeast have relied on incomplete assemblies of Mediator and/or pol II and have yielded inconsistent interpretations. We have assembled the complete, 1.9 MDa human Mediator-pol II-TFIIF complex from purified components and have characterized its structural organization using cryo-electron microscopy and single-particle reconstruction techniques. The orientation of pol II within this assembly was determined by crystal structure docking and further validated with projection matching experiments, allowing the structural organization of the entire human PIC to be envisioned. Significantly, pol II orientation within the Mediator-pol II-TFIIF assembly can be reconciled with past studies that determined the location of other PIC components relative to pol II itself. Pol II surfaces required for interacting with TFIIB, TFIIE, and promoter DNA (i.e., the pol II cleft) are exposed within the Mediator-pol II-TFIIF structure; RNA exit is unhindered along the RPB4/7 subunits; upstream and downstream DNA is accessible for binding additional factors; and no major structural re-organization is necessary to accommodate the large, multi-subunit TFIIH or TFIID complexes. The data also reveal how pol II binding excludes Mediator-CDK8 subcomplex interactions and provide a structural basis for Mediator-dependent control of PIC assembly and function. Finally, parallel structural analysis of Mediator-pol II complexes lacking TFIIF reveal that TFIIF plays a key role in stabilizing pol II orientation within the assembly.

Molecular Architecture of the Human Mediator–RNA Polymerase II–TFIIF Assembly

PubMed Central

Bernecky, Carrie; Grob, Patricia; Ebmeier, Christopher C.; Nogales, Eva; Taatjes, Dylan J.

2011-01-01

The macromolecular assembly required to initiate transcription of protein-coding genes, known as the Pre-Initiation Complex (PIC), consists of multiple protein complexes and is approximately 3.5 MDa in size. At the heart of this assembly is the Mediator complex, which helps regulate PIC activity and interacts with the RNA polymerase II (pol II) enzyme. The structure of the human Mediator–pol II interface is not well-characterized, whereas attempts to structurally define the Mediator–pol II interaction in yeast have relied on incomplete assemblies of Mediator and/or pol II and have yielded inconsistent interpretations. We have assembled the complete, 1.9 MDa human Mediator–pol II–TFIIF complex from purified components and have characterized its structural organization using cryo-electron microscopy and single-particle reconstruction techniques. The orientation of pol II within this assembly was determined by crystal structure docking and further validated with projection matching experiments, allowing the structural organization of the entire human PIC to be envisioned. Significantly, pol II orientation within the Mediator–pol II–TFIIF assembly can be reconciled with past studies that determined the location of other PIC components relative to pol II itself. Pol II surfaces required for interacting with TFIIB, TFIIE, and promoter DNA (i.e., the pol II cleft) are exposed within the Mediator–pol II–TFIIF structure; RNA exit is unhindered along the RPB4/7 subunits; upstream and downstream DNA is accessible for binding additional factors; and no major structural re-organization is necessary to accommodate the large, multi-subunit TFIIH or TFIID complexes. The data also reveal how pol II binding excludes Mediator–CDK8 subcomplex interactions and provide a structural basis for Mediator-dependent control of PIC assembly and function. Finally, parallel structural analysis of Mediator–pol II complexes lacking TFIIF reveal that TFIIF plays a key role in stabilizing pol II orientation within the assembly. PMID:21468301

Efficiency and Fidelity of Human DNA Polymerases λ and β during Gap-Filling DNA Synthesis

PubMed Central

Brown, Jessica A.; Pack, Lindsey R.; Sanman, Laura E.; Suo, Zucai

2010-01-01

The base excision repair (BER) pathway coordinates the replacement of 1 to 10 nucleotides at sites of single-base lesions. This process generates DNA substrates with various gap sizes which can alter the catalytic efficiency and fidelity of a DNA polymerase during gap-filling DNA synthesis. Here, we quantitatively determined the substrate specificity and base substitution fidelity of human DNA polymerase λ (Pol λ), an enzyme proposed to support the known BER DNA polymerase β (Pol β), as it filled 1- to 10-nucleotide gaps at 1-nucleotide intervals. Pol λ incorporated a correct nucleotide with relatively high efficiency until the gap size exceeded 9 nucleotides. Unlike Pol λ, Pol β did not have an absolute threshold on gap size as the catalytic efficiency for a correct dNTP gradually decreased as the gap size increased from 2 to 10 nucleotides and then recovered for non-gapped DNA. Surprisingly, an increase in gap size resulted in lower polymerase fidelity for Pol λ, and this downregulation of fidelity was controlled by its non-enzymatic N-terminal domains. Overall, Pol λ was up to 160-fold more error-prone than Pol β, thereby suggesting Pol λ would be more mutagenic during long gap-filling DNA synthesis. In addition, dCTP was the preferred misincorporation for Pol λ and its N-terminal domain truncation mutants. This nucleotide preference was shown to be dependent upon the identity of the adjacent 5′-template base. Our results suggested that both Pol λ and Pol β would catalyze nucleotide incorporation with the highest combination of efficiency and accuracy when the DNA substrate contains a single-nucleotide gap. Thus, Pol λ, like Pol β, is better suited to catalyze gap-filling DNA synthesis during short-patch BER in vivo, although, Pol λ may play a role in long-patch BER. PMID:20961817

Crystal Structures of Mite Allergens Der f 1 and Der p 1 Reveal Differences in Surface-Exposed Residues that May Influence Antibody Binding

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

Chruszcz, Maksymilian; Chapman, Martin D.; Vailes, Lisa D.

2009-12-01

The Group 1 mite allergens, Der f 1 and Der p 1, are potent allergens excreted by Dermatophagoides farinae and Dermatophagoides pteronyssinus, respectively. The human IgE antibody responses to the Group 1 allergens show more cross-reactivity than the murine IgG antibody responses which are largely species-specific. Here, we report the crystal structure of the mature form of Der f 1, which was isolated from its natural source, and a new, high-resolution structure of mature recombinant Der p 1. Unlike Der p 1, Der f 1 is monomeric both in the crystalline state and in solution. Moreover, no metal binding ismore » observed in the structure of Der f 1, despite the fact that all amino acids involved in Ca{sup 2+} binding in Der p 1 are completely conserved in Der f 1. Although Der p 1 and Der f 1 share extensive sequence identity, comparison of the crystal structures of both allergens revealed structural features which could explain the differences in murine and human IgE antibody responses to these allergens. There are structural differences between Der f 1 and Der p 1 which are unevenly distributed on the allergens' surfaces. This uneven spatial arrangement of conserved versus altered residues could explain both the specificity and cross-reactivity of antibodies against Der f 1 and Der p 1.« less

Recent Improvements to the Finite-Fault Rupture Detector Algorithm: FinDer II

NASA Astrophysics Data System (ADS)

Smith, D.; Boese, M.; Heaton, T. H.

2015-12-01

Constraining the finite-fault rupture extent and azimuth is crucial for accurately estimating ground-motion in large earthquakes. Detecting and modeling finite-fault ruptures in real-time is thus essential to both earthquake early warning (EEW) and rapid emergency response. Following extensive real-time and offline testing, the finite-fault rupture detector algorithm, FinDer (Böse et al., 2012 & 2015), was successfully integrated into the California-wide ShakeAlert EEW demonstration system. Since April 2015, FinDer has been scanning real-time waveform data from approximately 420 strong-motion stations in California for peak ground acceleration (PGA) patterns indicative of earthquakes. FinDer analyzes strong-motion data by comparing spatial images of observed PGA with theoretical templates modeled from empirical ground-motion prediction equations (GMPEs). If the correlation between the observed and theoretical PGA is sufficiently high, a report is sent to ShakeAlert including the estimated centroid position, length, and strike, and their uncertainties, of an ongoing fault rupture. Rupture estimates are continuously updated as new data arrives. As part of a joint effort between USGS Menlo Park, ETH Zurich, and Caltech, we have rewritten FinDer in C++ to obtain a faster and more flexible implementation. One new feature of FinDer II is that multiple contour lines of high-frequency PGA are computed and correlated with templates, allowing the detection of both large earthquakes and much smaller (~ M3.5) events shortly after their nucleation. Unlike previous EEW algorithms, FinDer II thus provides a modeling approach for both small-magnitude point-source and larger-magnitude finite-fault ruptures with consistent error estimates for the entire event magnitude range.

Transporterscheinungen

NASA Astrophysics Data System (ADS)

Heintze, Joachim

In diesem Kapitel werden wir uns vornehmlich mit zwei Vorgängen befassen, ohne die das Erreichen des thermischen Gleichgewichts und die Veränderung des thermischen Zustands eines Systems unmöglich wäre: Wärmeleitung und Diffusion. Bei der Wärmeleitung wird die kinetische Energie der Teilchen durch Stöße auf die Nachbarn übertragen: Es handelt sich um den Transport von Wärmeenergie. Unter Diffusion versteht man den Transport von Molekülen aufgrund ihrer Wärmebewegung. Sie tritt in Erscheinung, wenn in einem System verschiedene Arten von Molekülen vorhanden und ungleichmäßig verteilt sind.

Classification Comparisons Between Compact Polarimetric and Quad-Pol SAR Imagery

NASA Astrophysics Data System (ADS)

Souissi, Boularbah; Doulgeris, Anthony P.; Eltoft, Torbjørn

2015-04-01

Recent interest in dual-pol SAR systems has lead to a novel approach, the so-called compact polarimetric imaging mode (CP) which attempts to reconstruct fully polarimetric information based on a few simple assumptions. In this work, the CP image is simulated from the full quad-pol (QP) image. We present here the initial comparison of polarimetric information content between QP and CP imaging modes. The analysis of multi-look polarimetric covariance matrix data uses an automated statistical clustering method based upon the expectation maximization (EM) algorithm for finite mixture modeling, using the complex Wishart probability density function. Our results showed that there are some different characteristics between the QP and CP modes. The classification is demonstrated using a E-SAR and Radarsat2 polarimetric SAR images acquired over DLR Oberpfaffenhofen in Germany and Algiers in Algeria respectively.

SOUTH POL: Revealing the Polarized Southern Sky

NASA Astrophysics Data System (ADS)

Magalhães, A. M.

2014-10-01

SOUTH POL will be a survey of the Southern sky in optical polarized light. It will use a newly designed polarimeter for an 80cm Robotic Telescope. Telescope and polarimeter will be installed at CTIO, Chile. The initial goal is to cover the sky south of declination -15° in about two years of observing time, aiming at a polarimetric accuracy ≤ 0.1% down to V=15, with a camera covering a field of about 2.0 square degrees. SOUTH POL will impact areas such as Cosmology, Extragalactic Astronomy, Interstellar Medium of the Galaxy and Magellanic Clouds, Star Formation, Stellar Envelopes, Stellar Explosions and Solar System, among others. The polarimeter is currently being built and its optics and electronics assembled. We will describe the current status of the project. This project is supported by FAPESP. AMM is also supported by CNPq.

Two distinct mechanisms ensure transcriptional polarity in double-stranded RNA bacteriophages.

PubMed

Yang, Hongyan; Makeyev, Eugene V; Butcher, Sarah J; Gaidelyte, Ausra; Bamford, Dennis H

2003-01-01

In most double-stranded RNA (dsRNA) viruses, RNA transcription occurs inside a polymerase (Pol) complex particle, which contains an RNA-dependent RNA Pol subunit as a minor component. Only plus- but not minus-sense copies of genomic segments are produced during this reaction. In the case of phi6, a dsRNA bacteriophage from the Cystoviridae family, isolated Pol synthesizes predominantly plus strands using virus-specific dsRNAs in vitro, thus suggesting that Pol template preferences determine the transcriptional polarity. Here, we dissect transcription reactions catalyzed by Pol complexes and Pol subunits of two other cystoviruses, phi8 and phi13. While both Pol complexes synthesize exclusively plus strands over a wide range of conditions, isolated Pol subunits can be stimulated by Mn(2+) to produce minus-sense copies on phi13 dsRNA templates. Importantly, all three Pol subunits become more prone to the native-like plus-strand synthesis when the dsRNA templates (including phi13 dsRNA) are activated by denaturation before the reaction. Based on these and earlier observations, we propose a model of transcriptional polarity in Cystoviridae controlled on two independent levels: Pol affinity to plus-strand initiation sites and accessibility of these sites to the Pol in a single-stranded form.

Two Distinct Mechanisms Ensure Transcriptional Polarity in Double-Stranded RNA Bacteriophages

PubMed Central

Yang, Hongyan; Makeyev, Eugene V.; Butcher, Sarah J.; Gaidelyte·, Aušra; Bamford, Dennis H.

2003-01-01

In most double-stranded RNA (dsRNA) viruses, RNA transcription occurs inside a polymerase (Pol) complex particle, which contains an RNA-dependent RNA Pol subunit as a minor component. Only plus- but not minus-sense copies of genomic segments are produced during this reaction. In the case of φ6, a dsRNA bacteriophage from the Cystoviridae family, isolated Pol synthesizes predominantly plus strands using virus-specific dsRNAs in vitro, thus suggesting that Pol template preferences determine the transcriptional polarity. Here, we dissect transcription reactions catalyzed by Pol complexes and Pol subunits of two other cystoviruses, φ8 and φ13. While both Pol complexes synthesize exclusively plus strands over a wide range of conditions, isolated Pol subunits can be stimulated by Mn2+ to produce minus-sense copies on φ13 dsRNA templates. Importantly, all three Pol subunits become more prone to the native-like plus-strand synthesis when the dsRNA templates (including φ13 dsRNA) are activated by denaturation before the reaction. Based on these and earlier observations, we propose a model of transcriptional polarity in Cystoviridae controlled on two independent levels: Pol affinity to plus-strand initiation sites and accessibility of these sites to the Pol in a single-stranded form. PMID:12502836

N-terminal domains of human DNA polymerase lambda promote primer realignment during translesion DNA synthesis

PubMed Central

Taggart, David J.; Dayeh, Daniel M.; Fredrickson, Saul W.; Suo, Zucai

2014-01-01

The X-family DNA polymerases λ (Polλ) and β (Polβ) possess similar 5′-2-deoxyribose-5-phosphatelyase (dRPase) and polymerase domains. Besides these domains, Polλ also possesses a BRCA1 C-terminal (BRCT) domain and a proline-rich domain at its N terminus. However, it is unclear how these non-enzymatic domains contribute to the unique biological functions of Polλ. Here, we used primer extension assays and a newly developed high-throughput short oligonucleotide sequencing assay (HT-SOSA) to compare the efficiency of lesion bypass and fidelity of human Polβ, Polλ and two N-terminal deletion constructs of Polλ during the bypass of either an abasic site or a 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) lesion. We demonstrate that the BRCT domain of Polλ enhances the efficiency of abasic site bypass by approximately 1.6-fold. In contrast, deletion of the N-terminal domains of Polλ did not affect the efficiency of 8-oxodG bypass relative to nucleotide incorporations opposite undamaged dG. HT-SOSA analysis demonstrated that Polλ and Polβ preferentially generated −1 or −2 frameshift mutations when bypassing an abasic site and the single or double base deletion frequency was highly sequence dependent. Interestingly, the BRCT and proline-rich domains of Polλ cooperatively promoted the generation of −2 frameshift mutations when the abasic site was situated within a sequence context that was susceptible to homology-driven primer realignment. Furthermore, both N-terminal domains of Polλ increased the generation of −1 frameshift mutations during 8-oxodG bypass and influenced the frequency of substitution mutations produced by Polλ opposite the 8-oxodG lesion. Overall, our data support a model wherein the BRCT and proline-rich domains of Polλ act cooperatively to promote primer/template realignment between DNA strands of limited sequence homology. This function of the N-terminal domains may facilitate the role of Polλ as a gap-filling polymerase within the non-homologous end joining pathway. PMID:25108835

Energy manager design for microgrids

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

Firestone, Ryan; Marnay, Chris

2005-01-01

On-site energy production, known as distributed energy resources (DER), offers consumers many benefits, such as bill savings and predictability, improved system efficiency, improved reliability, control over power quality, and in many cases, greener electricity. Additionally, DER systems can benefit electric utilities by reducing congestion on the grid, reducing the need for new generation and transmission capacity, and offering ancillary services such as voltage support and emergency demand response. Local aggregations of distributed energy resources (DER) that may include active control of on-site end-use energy devices can be called microgrids. Microgrids require control to ensure safe operation and to make dispatchmore » decisions that achieve system objectives such as cost minimization, reliability, efficiency and emissions requirements, while abiding by system constraints and regulatory rules. This control is performed by an energy manager (EM). Preferably, an EM will achieve operation reasonably close to the attainable optimum, it will do this by means robust to deviations from expected conditions, and it will not itself incur insupportable capital or operation and maintenance costs. Also, microgrids can include supervision over end-uses, such as curtailing or rescheduling certain loads. By viewing a unified microgrid as a system of supply and demand, rather than simply a system of on-site generation devices, the benefits of integrated supply and demand control can be exploited, such as economic savings and improved system energy efficiency.« less

Mechanism of Adenomatous Polyposis Coli (APC)-mediated Blockage of Longpatch Base Excision Repair†

PubMed Central

Jaiswal, Aruna S.; Balusu, Ramesh; Armas, Melissa L.; Kundu, Chanakya N.; Narayan, Satya

2008-01-01

Recently, we found an interaction between adenomatous polyposis coli (APC) and DNA polymerase β (pol-β) and showed that APC blocks strand-displacement synthesis of long-patch base excision repair (LP-BER) however, the mechanism is not clear. Using an in vivo LP-BER assay system, we now show that the LP-BER is higher in APC−/− cells than in APC+/+ cells. In addition to pol-β, the pull-down experiments showed that the full-length APC also interacted with flap endonuclease 1 (Fen-1). To further characterize the interaction of APC with pol-β and Fen-1, we performed a domain-mapping of APC and found that both pol-β and Fen-1 interact with a 138-amino acids peptide from the APC at the DRI-domain. Our functional assays showed that APC blocks pol-β-mediated 1-nucleotide (1-nt) as well as strand-displacement synthesis of reduced abasic, nicked-, or 1-nt gapped-DNA substrates. Our further studies demonstrated that APC blocks 5′-flap endonuclease as well as 5′-3′ exonuclease activity of Fen-1 resulting in the blockage of LP-BER. From these results we concluded that APC can have three different effects in the LP-BER pathway. First, APC can block pol-β-mediated 1-nt incorporation and strand-displacement synthesis. Second, APC can block LP-BER by blocking coordinated formation and removal of the strand-displaced flap. Third, APC can block LP-BER by blocking “Hit and Run” synthesis. These studies will have important implications of APC in DNA damage-induced carcinogenesis and chemoprevention. PMID:17176113

DNA Polymerase β as a Novel Target for Chemotherapeutic Intervention of Colorectal Cancer

PubMed Central

Jaiswal, Aruna S.; Banerjee, Sanjeev; Aneja, Ritu; Sarkar, Fazlul H.; Ostrov, David A.; Narayan, Satya

2011-01-01

Chemoprevention presents a major strategy for the medical management of colorectal cancer. Most drugs used for colorectal cancer therapy induce DNA-alkylation damage, which is primarily repaired by the base excision repair (BER) pathway. Thus, blockade of BER pathway is an attractive option to inhibit the spread of colorectal cancer. Using an in silico approach, we performed a structure-based screen by docking small-molecules onto DNA polymerase β (Pol-β) and identified a potent anti-Pol-β compound, NSC-124854. Our goal was to examine whether NSC-124854 could enhance the therapeutic efficacy of DNA-alkylating agent, Temozolomide (TMZ), by blocking BER. First, we determined the specificity of NSC-124854 for Pol-β by examining in vitro activities of APE1, Fen1, DNA ligase I, and Pol-β-directed single nucleotide (SN)- and long-patch (LP)-BER. Second, we investigated the effect of NSC-124854 on the efficacy of TMZ to inhibit the growth of mismatch repair (MMR)-deficient and MMR-proficient colon cancer cell lines using in vitro clonogenic assays. Third, we explored the effect of NSC-124854 on TMZ-induced in vivo tumor growth inhibition of MMR-deficient and MMR-proficient colonic xenografts implanted in female homozygous SCID mice. Our data showed that NSC-124854 has high specificity to Pol-β and blocked Pol-β-directed SN- and LP-BER activities in in vitro reconstituted system. Furthermore, NSC-124854 effectively induced the sensitivity of TMZ to MMR-deficient and MMR-proficient colon cancer cells both in vitro cell culture and in vivo xenograft models. Our findings suggest a potential novel strategy for the development of highly specific structure-based inhibitor for the prevention of colonic tumor progression. PMID:21311763

Werner Heisenberg zum 100. Geburtstag: Pionier der Quantenmechanik

NASA Astrophysics Data System (ADS)

Jacobi, Manfred

2001-11-01

Werner Heisenberg war eine der prägendsten Gestalten der Physik des 20. Jahrhunderts. Zu seinen wichtigsten Verdiensten gehören die Grundlegung der Quantenmechanik, die Formulierung der Unschärferelationen sowie die Beteiligung an der Ausarbeitung der Kopenhagener Deutung der Quantenmechanik. Darüber hinaus lieferte er Arbeiten von fundamentalem Charakter zur Theorie des Atomkerns, zur kosmischen Strahlung und zur Quantenfeldtheorie. Während des Krieges war er an den Arbeiten des Uranvereins beteiligt, der die Möglichkeit einer Entwicklung von Kernwaffen untersuchte, jedoch über Vorarbeiten zur Reaktorphysik nicht hinauskam. Wegen dieser Tätigkeit wurde er bei Kriegsende für einige Monate in England interniert. Nach seiner Rückkehr widmete er sich vor allem dem Aufbau der Physik in Deutschland, die während der NS-Zeit nahezu ihrer gesamten Substanz beraubt worden war.

Functional diversification of maize RNA polymerase IV and V subtypes via alternative catalytic subunits

DOE PAGES

Haag, Jeremy R.; Brower-Toland, Brent; Krieger, Elysia K.; ...

2014-10-02

Unlike nuclear multisubunit RNA polymerases I, II, and III, whose subunit compositions are conserved throughout eukaryotes, plant RNA polymerases IV and V are nonessential, Pol II-related enzymes whose subunit compositions are still evolving. Whereas Arabidopsis Pols IV and V differ from Pol II in four or five of their 12 subunits, respectively, and differ from one another in three subunits, proteomic analyses show that maize Pols IV and V differ from Pol II in six subunits but differ from each other only in their largest subunits. Use of alternative catalytic second subunits, which are nonredundant for development and paramutation, yieldsmore » at least two sub-types of Pol IV and three subtypes of Pol V in maize. Pol IV/Pol V associations with MOP1, RMR1, AGO121, Zm_DRD1/CHR127, SHH2a, and SHH2b extend parallels between paramutation in maize and the RNA-directed DNA methylation pathway in Arabidopsis.« less

Live-cell analysis of endogenous GFP-RPB1 uncovers rapid turnover of initiating and promoter-paused RNA Polymerase II.

PubMed

Steurer, Barbara; Janssens, Roel C; Geverts, Bart; Geijer, Marit E; Wienholz, Franziska; Theil, Arjan F; Chang, Jiang; Dealy, Shannon; Pothof, Joris; van Cappellen, Wiggert A; Houtsmuller, Adriaan B; Marteijn, Jurgen A

2018-05-08

Initiation and promoter-proximal pausing are key regulatory steps of RNA Polymerase II (Pol II) transcription. To study the in vivo dynamics of endogenous Pol II during these steps, we generated fully functional GFP-RPB1 knockin cells. GFP-RPB1 photobleaching combined with computational modeling revealed four kinetically distinct Pol II fractions and showed that on average 7% of Pol II are freely diffusing, while 10% are chromatin-bound for 2.4 seconds during initiation, and 23% are promoter-paused for only 42 seconds. This unexpectedly high turnover of Pol II at promoters is most likely caused by premature termination of initiating and promoter-paused Pol II and is in sharp contrast to the 23 minutes that elongating Pol II resides on chromatin. Our live-cell-imaging approach provides insights into Pol II dynamics and suggests that the continuous release and reinitiation of promoter-bound Pol II is an important component of transcriptional regulation. Copyright © 2018 the Author(s). Published by PNAS.

Long non-coding RNA produced by RNA polymerase V determines boundaries of heterochromatin

PubMed Central

Böhmdorfer, Gudrun; Sethuraman, Shriya; Rowley, M Jordan; Krzyszton, Michal; Rothi, M Hafiz; Bouzit, Lilia; Wierzbicki, Andrzej T

2016-01-01

RNA-mediated transcriptional gene silencing is a conserved process where small RNAs target transposons and other sequences for repression by establishing chromatin modifications. A central element of this process are long non-coding RNAs (lncRNA), which in Arabidopsis thaliana are produced by a specialized RNA polymerase known as Pol V. Here we show that non-coding transcription by Pol V is controlled by preexisting chromatin modifications located within the transcribed regions. Most Pol V transcripts are associated with AGO4 but are not sliced by AGO4. Pol V-dependent DNA methylation is established on both strands of DNA and is tightly restricted to Pol V-transcribed regions. This indicates that chromatin modifications are established in close proximity to Pol V. Finally, Pol V transcription is preferentially enriched on edges of silenced transposable elements, where Pol V transcribes into TEs. We propose that Pol V may play an important role in the determination of heterochromatin boundaries. DOI: http://dx.doi.org/10.7554/eLife.19092.001 PMID:27779094

Bereits nach Ablauf der Halbwertszeit droht der vollständige Zerfall Die britische Atomic Scientists’ Association, die Ideologie der „objektiven” Wissenschaft und die H-Bombe

NASA Astrophysics Data System (ADS)

Laucht, Christoph

Präsident Harry Trumans Verlautbarung vom 31.1.1950, seine Regierung wolle die Entwicklung der Wasserstoffbombe vorantreiben, fand große Beachtung in den britischen Medien. Die illustrierte Zeitschrift Picture Post widmete der HBombe einen Artikel, der unter anderem kurze Stellungnahmen der britischen Atomwissenschaftler Eric Burhop, Kathleen Lonsdale, Harrie Massey, Rudolf Peierls und Maurice Pryce enthielt, die alle Mitglieder der Atomic Scientists' Association (ASA) waren.

The effect of the London-van der Waals dispersion force on interline heat transfer

NASA Technical Reports Server (NTRS)

Wayner, P. C., Jr.

1978-01-01

A theoretical procedure to determine the heat transfer characteristics of the interline region (junction of liquid-solid-vapor) from the macroscopic optical and thermophysical properties of the system is outlined. The analysis is based on the premise that the interline transport processes are controlled by the London-van der Waals dispersion force between condensed phases (solid and liquid). Numerical values of the dispersion constant are presented. The procedure is used to compare the relative size of the interline heat sink of various systems using a constant heat flux mode. This solution demonstrates the importance of the interline heat flow number, which is evaluated for various systems.

The impact of short-term stochastic variability in solar irradiance on optimal microgrid design

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

Schittekatte, Tim; Stadler, Michael; Cardoso, Gonçalo

2016-07-01

This paper proposes a new methodology to capture the impact of fast moving clouds on utility power demand charges observed in microgrids with photovoltaic (PV) arrays, generators, and electrochemical energy storage. It consists of a statistical approach to introduce sub-hourly events in the hourly economic accounting process. The methodology is implemented in the Distributed Energy Resources Customer Adoption Model (DER-CAM), a state of the art mixed integer linear model used to optimally size DER in decentralized energy systems. Results suggest that previous iterations of DER-CAM could undersize battery capacities. The improved model depicts more accurately the economic value of PVmore » as well as the synergistic benefits of pairing PV with storage.« less

Transient expression and activity of human DNA polymerase iota in loach embryos.

PubMed

Makarova, Irina V; Kazakov, Andrey A; Makarova, Alena V; Khaidarova, Nella V; Kozikova, Larisa V; Nenasheva, Valentina V; Gening, Leonid V; Tarantul, Vyacheslav Z; Andreeva, Ludmila E

2012-02-01

Human DNA polymerase iota (Pol ι) is a Y-family DNA polymerase with unusual biochemical properties and not fully understood functions. Pol ι preferentially incorporates dGTP opposite template thymine. This property can be used to monitor Pol ι activity in the presence of other DNA polymerases, e.g. in cell extracts of tissues and tumors. We have now confirmed the specificity and sensitivity of the method of Pol ι activity detection in cell extracts using an animal model of loach Misgurnus fossilis embryos transiently expressing human Pol ι. The overexpression of Pol ι was shown to be accompanied by an increase in abnormalities in development and the frequency of pycnotic nuclei in fish embryos. Further analysis of fish embryos with constitutive or regulated Pol ι expression may provide insights into Pol ι functions in vertebrate animals.

Solution Structures of 2 : 1 And 1 : 1 DNA Polymerase - DNA Complexes Probed By Ultracentrifugation And Small-Angle X-Ray Scattering

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

Tang, K.H.; /Ohio State U.; Niebuhr, M.

2009-04-30

We report small-angle X-ray scattering (SAXS) and sedimentation velocity (SV) studies on the enzyme-DNA complexes of rat DNA polymerase {beta} (Pol {beta}) and African swine fever virus DNA polymerase X (ASFV Pol X) with one-nucleotide gapped DNA. The results indicated formation of a 2 : 1 Pol {beta}-DNA complex, whereas only 1 : 1 Pol X-DNA complex was observed. Three-dimensional structural models for the 2 : 1 Pol {beta}-DNA and 1 : 1 Pol X-DNA complexes were generated from the SAXS experimental data to correlate with the functions of the DNA polymerases. The former indicates interactions of the 8 kDamore » 5{prime}-dRP lyase domain of the second Pol {beta} molecule with the active site of the 1 : 1 Pol {beta}-DNA complex, while the latter demonstrates how ASFV Pol X binds DNA in the absence of DNA-binding motif(s). As ASFV Pol X has no 5{prime}-dRP lyase domain, it is reasonable not to form a 2 : 1 complex. Based on the enhanced activities of the 2 : 1 complex and the observation that the 8 kDa domain is not in an optimal configuration for the 5{prime}-dRP lyase reaction in the crystal structures of the closed ternary enzyme-DNA-dNTP complexes, we propose that the asymmetric 2 : 1 Pol {beta}-DNA complex enhances the function of Pol {beta}.« less

Inhibition of DNA polymerase λ and associated inflammatory activities of extracts from steamed germinated soybeans.

PubMed

Mizushina, Yoshiyuki; Kuriyama, Isoko; Yoshida, Hiromi

2014-04-01

During the screening of selective DNA polymerase (pol) inhibitors from more than 50 plant food materials, we found that the extract from steamed germinated soybeans (Glycine max L.) inhibited human pol λ activity. Among the three processed soybean samples tested (boiled soybeans, steamed soybeans, and steamed germinated soybeans), both the hot water extract and organic solvent extract from the steamed germinated soybeans had the strongest pol λ inhibition. We previously isolated two glucosyl compounds, a cerebroside (glucosyl ceramide, AS-1-4, compound ) and a steroidal glycoside (eleutheroside A, compound ), from dried soybean, and these compounds were prevalent in the extracts of the steamed germinated soybeans as pol inhibitors. The hot water and organic solvent extracts of the steamed germinated soybeans and compounds and selectively inhibited the activity of eukaryotic pol λ in vitro but did not influence the activities of other eukaryotic pols, including those from the A-family (pol γ), B-family (pols α, δ, and ε), and Y-family (pols η, ι, and κ), and also showed no effect on the activity of pol β, which is of the same family (X) as pol λ. The tendency for in vitro pol λ inhibition by these extracts and compounds showed a positive correlation with the in vivo suppression of TPA (12-O-tetradecanoylphorbol-13-acetate)-induced inflammation in mouse ear. These results suggest that steamed germinated soybeans, especially the glucosyl compound components, may be useful for their anti-inflammatory properties.

An ATP-dependent ligase with substrate flexibility involved in assembly of the peptidyl nucleoside antibiotic polyoxin.

PubMed

Gong, Rong; Qi, Jianzhao; Wu, Pan; Cai, You-Sheng; Ma, Hongmin; Liu, Yang; Duan, He; Wang, Meng; Deng, Zixin; Price, Neil P J; Chen, Wenqing

2018-04-27

Polyoxin (POL) is an unusual peptidyl nucleoside antibiotic, in which peptidyl moiety and nucleoside skeleton are linked by an amide bond. However, their biosynthesis remains poorly understood. Here, we report the deciphering of PolG as an ATP-dependent ligase responsible for the assembly of POL. A polG mutant is capable of accumulating multiple intermediates, including the peptidyl moiety (carbamoylpolyoxamic acid, CPOAA) and the nucleosides skeletons (POL-C and the previously overlooked thymine POL-C). We further demonstrated that PolG employs an ATP-dependent mechanism for amide bond formation, and that the generation of the hybrid nucleoside antibiotic, POL-N, is also governed by PolG. Finally, we determined that the deduced ATP-binding sites are functionally essential for PolG, and that they are highly conserved in a number of related ATP-dependent ligases. These insights have allowed us proposed a catalytic mechanism for the assembly of peptidyl nucleoside antibiotic via an acyl-phosphate intermediate, and have opened the way for the combinatorial biosynthesis/pathway engineering of this group of nucleoside antibiotics. Importance POL is well known for its remarkable antifungal bioactivities and unusual structural features. Actually, elucidation of the POL assembly logic not only provides the enzymatic basis for further biosynthetic understanding of related peptidyl nucleoside antibiotics, but also contributes to the rational generation of more hybrid nucleoside antibiotics via synthetic biology strategy. Copyright © 2018 American Society for Microbiology.

DNA polymerase iota (Pol ι) promotes invasion and metastasis of esophageal squamous cell carcinoma.

PubMed

Zou, Shitao; Shang, Zeng-Fu; Liu, Biao; Zhang, Shuyu; Wu, Jinchang; Huang, Min; Ding, Wei-Qun; Zhou, Jundong

2016-05-31

DNA polymerase iota (Pol ι) is an error-prone DNA polymerase involved in translesion DNA synthesis (TLS) that contributes to the accumulation of DNA mutations. We recently showed that Pol ι is overexpressed in human esophageal squamous cell cancer (ESCC) tissues which promotes ESCC' progression. The present study was aimed at investigating the molecular mechanisms by which Pol ι enhances the invasiveness and metastasis of ESCC cells. We found that the expression of Pol ι is significantly higher in ESCCs with lymph node metastasis compared to those without lymph node metastasis. Kaplan-Meier analysis revealed an inverse correlation between Pol ι expression and patient prognosis. The expression levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two essential regulators of cells' invasiveness, were positively associated with Pol ι expression in ESCC tissues. Ectopic expression of Pol ι enhanced the motility and invasiveness of ESCC cells as evaluated by wound-healing and transwell assays, respectively. A xenograft nude mouse model showed that Pol ι promotes the colonization of ESCC cells in the liver, lung and kidney. Signaling pathway analysis identified the JNK-AP-1 cascade as a mediator of the Pol ι-induced increase in the expression of MMP-2/9 and enhancement of ESCC progression. These data demonstrate the underlying mechanism by which Pol ι promotes ESCC progression, suggesting that Pol ι is a potential novel prognostic biomarker and therapeutic target for ESCC.

DNA polymerase iota (Pol ι) promotes invasion and metastasis of esophageal squamous cell carcinoma

PubMed Central

Liu, Biao; Zhang, Shuyu; Wu, Jinchang; Huang, Min; Ding, Wei-Qun; Zhou, Jundong

2016-01-01

DNA polymerase iota (Pol ι) is an error-prone DNA polymerase involved in translesion DNA synthesis (TLS) that contributes to the accumulation of DNA mutations. We recently showed that Pol ι is overexpressed in human esophageal squamous cell cancer (ESCC) tissues which promotes ESCC' progression. The present study was aimed at investigating the molecular mechanisms by which Pol ι enhances the invasiveness and metastasis of ESCC cells. We found that the expression of Pol ι is significantly higher in ESCCs with lymph node metastasis compared to those without lymph node metastasis. Kaplan-Meier analysis revealed an inverse correlation between Pol ι expression and patient prognosis. The expression levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two essential regulators of cells' invasiveness, were positively associated with Pol ι expression in ESCC tissues. Ectopic expression of Pol ι enhanced the motility and invasiveness of ESCC cells as evaluated by wound-healing and transwell assays, respectively. A xenograft nude mouse model showed that Pol ι promotes the colonization of ESCC cells in the liver, lung and kidney. Signaling pathway analysis identified the JNK-AP-1 cascade as a mediator of the Pol ι-induced increase in the expression of MMP-2/9 and enhancement of ESCC progression. These data demonstrate the underlying mechanism by which Pol ι promotes ESCC progression, suggesting that Pol ι is a potential novel prognostic biomarker and therapeutic target for ESCC. PMID:27057634

Einstellung und Wissen von Lehramtsstudierenden zur Evolution - ein Vergleich zwischen Deutschland und der Türkei

NASA Astrophysics Data System (ADS)

Graf, Dittmar; Soran, Haluk

Es wird eine Untersuchung vorgestellt, in der Wissen und Überzeugungen von Lehramtsstudierenden aller Fächer zum Thema Evolution an zwei Universitäten in Deutschland und der Türkei erhoben worden sind. Die Befragung wurde in Dortmund und in Ankara durchgeführt. Es stellte sich heraus, dass ausgeprägte Defizite im Verständnis der Evolutionsmechanismen herrschen. Viele Studierende, insbesondere aus der Türkei, sind nicht von der Faktizität der Evolution überzeugt. Dies gilt sowohl für Studierende mit Fach Biologie als auch für Studierende mit anderen Fächern. Näher untersucht worden sind die Faktoren, die die Überzeugungen zur Evolution beeinflussen können, was ja in Anbetracht der hohen Ablehnungsrate der Evolution von besonderem Interesse ist. Das Vertrauen in die Wissenschaft spielt hierbei eine besondere Rolle: Wer der Wissenschaft vertraut, ist auch eher von der Evolution überzeugt, als diejenigen, die skeptisch gegenüber der Wissenschaft sind.

Systems Training for Emotional Predictability and Problem Solving Program and Emotion Dysregulation: A Pilot Study.

PubMed

Boccalon, Silvia; Alesiani, Roberta; Giarolli, Laura; Fossati, Andrea

2017-03-01

The aim of this study was to assess the observed changes on emotion dysregulation obtained through the Systems Training for Emotional Predictability and Problem Solving (STEPPS) program. The sample is composed of 24 subjects with a personality disorder with borderline features. All participants filled out the Difficulties in Emotion Regulation Scale (DERS). There was a significant decrease in the DERS total score at the end of the treatment and at 6-month follow-up. Friedman test showed a significant decrease in suicide attempts and hospitalizations over time. The analysis of the DERS subscales showed that "goals" and "impulse" were the two dimensions on which the treatment acted and the changes were stable over time. STEPPS is associated with an improvement in emotion regulation and a reduction in the number of hospitalizations and suicide attempts. The treatment seems to act on the behavioral dimensions of emotion dysregulation like the ability to control impulsive behaviors and to achieve goals.

Nucleosome Positioning and NDR Structure at RNA Polymerase III Promoters

NASA Astrophysics Data System (ADS)

Helbo, Alexandra Søgaard; Lay, Fides D.; Jones, Peter A.; Liang, Gangning; Grønbæk, Kirsten

2017-02-01

Chromatin is structurally involved in the transcriptional regulation of all genes. While the nucleosome positioning at RNA polymerase II (pol II) promoters has been extensively studied, less is known about the chromatin structure at pol III promoters in human cells. We use a high-resolution analysis to show substantial differences in chromatin structure of pol II and pol III promoters, and between subtypes of pol III genes. Notably, the nucleosome depleted region at the transcription start site of pol III genes extends past the termination sequences, resulting in nucleosome free gene bodies. The +1 nucleosome is located further downstream than at pol II genes and furthermore displays weak positioning. The variable position of the +1 location is seen not only within individual cell populations and between cell types, but also between different pol III promoter subtypes, suggesting that the +1 nucleosome may be involved in the transcriptional regulation of pol III genes. We find that expression and DNA methylation patterns correlate with distinct accessibility patterns, where DNA methylation associates with the silencing and inaccessibility at promoters. Taken together, this study provides the first high-resolution map of nucleosome positioning and occupancy at human pol III promoters at specific loci and genome wide.

DNA polymerase ι functions in the generation of tandem mutations during somatic hypermutation of antibody genes.

PubMed

Maul, Robert W; MacCarthy, Thomas; Frank, Ekaterina G; Donigan, Katherine A; McLenigan, Mary P; Yang, William; Saribasak, Huseyin; Huston, Donald E; Lange, Sabine S; Woodgate, Roger; Gearhart, Patricia J

2016-08-22

DNA polymerase ι (Pol ι) is an attractive candidate for somatic hypermutation in antibody genes because of its low fidelity. To identify a role for Pol ι, we analyzed mutations in two strains of mice with deficiencies in the enzyme: 129 mice with negligible expression of truncated Pol ι, and knock-in mice that express full-length Pol ι that is catalytically inactive. Both strains had normal frequencies and spectra of mutations in the variable region, indicating that loss of Pol ι did not change overall mutagenesis. We next examined if Pol ι affected tandem mutations generated by another error-prone polymerase, Pol ζ. The frequency of contiguous mutations was analyzed using a novel computational model to determine if they occur during a single DNA transaction or during two independent events. Analyses of 2,000 mutations from both strains indicated that Pol ι-compromised mice lost the tandem signature, whereas C57BL/6 mice accumulated significant amounts of double mutations. The results support a model where Pol ι occasionally accesses the replication fork to generate a first mutation, and Pol ζ extends the mismatch with a second mutation. @2016.

DNA polymerase ι functions in the generation of tandem mutations during somatic hypermutation of antibody genes

PubMed Central

Donigan, Katherine A.; Huston, Donald E.; Lange, Sabine S.

2016-01-01

DNA polymerase ι (Pol ι) is an attractive candidate for somatic hypermutation in antibody genes because of its low fidelity. To identify a role for Pol ι, we analyzed mutations in two strains of mice with deficiencies in the enzyme: 129 mice with negligible expression of truncated Pol ι, and knock-in mice that express full-length Pol ι that is catalytically inactive. Both strains had normal frequencies and spectra of mutations in the variable region, indicating that loss of Pol ι did not change overall mutagenesis. We next examined if Pol ι affected tandem mutations generated by another error-prone polymerase, Pol ζ. The frequency of contiguous mutations was analyzed using a novel computational model to determine if they occur during a single DNA transaction or during two independent events. Analyses of 2,000 mutations from both strains indicated that Pol ι–compromised mice lost the tandem signature, whereas C57BL/6 mice accumulated significant amounts of double mutations. The results support a model where Pol ι occasionally accesses the replication fork to generate a first mutation, and Pol ζ extends the mismatch with a second mutation. PMID:27455952

The microbiology of mutability.

PubMed

Sundin, George W; Weigand, Michael R

2007-12-01

Bacteria possessing elevated spontaneous mutation rates are prevalent in certain environments, which is a paradox because most mutations are deleterious. For example, cells with defects in the methyl-directed mismatch repair (MMR) system, termed mutators or hypermutators, are overrepresented in populations of bacterial pathogens, with the mutator trait hypothesized to be advantageous in the changing host enviroments faced during colonization and establishment of chronic infections. Error-prone DNA polymerases, such as polIV and polV, function in translesion DNA synthesis, a DNA damage response that ensures genome integrity with a cost of increased mutation. While the biochemical aspects of these mutability pathways are well understood, the biological impacts have received less attention. Here, an examination of bacterial mutability systems and specifically the ecological and evolutionary context resulting in the selection of these systems is carried out.

DNA polymerases eta and kappa exchange with the polymerase delta holoenzyme to complete common fragile site synthesis.

PubMed

Barnes, Ryan P; Hile, Suzanne E; Lee, Marietta Y; Eckert, Kristin A

2017-09-01

Common fragile sites (CFSs) are inherently unstable genomic loci that are recurrently altered in human tumor cells. Despite their instability, CFS are ubiquitous throughout the human genome and associated with large tumor suppressor genes or oncogenes. CFSs are enriched with repetitive DNA sequences, one feature postulated to explain why these loci are inherently difficult to replicate, and sensitive to replication stress. We have shown that specialized DNA polymerases (Pols) η and κ replicate CFS-derived sequences more efficiently than the replicative Pol δ. However, we lacked an understanding of how these enzymes cooperate to ensure efficient CFS replication. Here, we designed a model of lagging strand replication with RFC loaded PCNA that allows for maximal activity of the four-subunit human Pol δ holoenzyme, Pol η, and Pol κ in polymerase mixing assays. We discovered that Pol η and κ are both able to exchange with Pol δ stalled at repetitive CFS sequences, enhancing Normalized Replication Efficiency. We used this model to test the impact of PCNA mono-ubiquitination on polymerase exchange, and found no change in polymerase cooperativity in CFS replication compared with unmodified PCNA. Finally, we modeled replication stress in vitro using aphidicolin and found that Pol δ holoenzyme synthesis was significantly inhibited in a dose-dependent manner, preventing any replication past the CFS. Importantly, Pol η and κ were still proficient in rescuing this stalled Pol δ synthesis, which may explain, in part, the CFS instability phenotype of aphidicolin-treated Pol η and Pol κ-deficient cells. In total, our data support a model wherein Pol δ stalling at CFSs allows for free exchange with a specialized polymerase that is not driven by PCNA. Copyright © 2017 Elsevier B.V. All rights reserved.

Kinetic Analysis of the Bypass of a Bulky DNA Lesion Catalyzed by Human Y-family DNA Polymerases

PubMed Central

Sherrer, Shanen M.; Sanman, Laura E.; Xia, Cynthia X.; Bolin, Eric R.; Malik, Chanchal K.; Efthimiopoulos, Georgia; Basu, Ashis K.; Suo, Zucai

2012-01-01

1-Nitropyrene (1-NP), a mutagen and potential carcinogen, is the most abundant nitro polyaromatic hydrocarbon in diesel exhaust, which reacts with DNA to form predominantly N-(deoxyguanosin-8-yl)-1-aminopyrene (dGAP). If not repaired, this DNA lesion is presumably bypassed in vivo by any of human Y-family DNA polymerases kappa (hPolκ), iota (hPolτ), eta (hPolη), and Rev1 (hRev1). Our running start assays demonstrated that each of these enzymes was indeed capable of traversing a site-specifically placed dGAP on a synthetic DNA template but hRev1 was stopped after lesion bypass. The time required to bypass 50% of the dGAP sites (t50bypass ) encountered by hPolη, hPolκ and hPolτ was determined to be 2.5 s, 4.1 s, and 106.5 s, respectively. The efficiency order of catalyzing translesion synthesis of dGAP (hPolη > hPolκ > hPolτ >> hRev1) is the same as the order for these human Y-family enzymes to elongate undamaged DNA. Although hPolη bypassed dGAP efficiently, replication by both hPolκ and hPolτ was strongly stalled at the lesion site and at a site immediately downstream from dGAP. By employing pre-steady state kinetic methods, a kinetic basis was established for polymerase pausing at these DNA template sites. Besides efficiency of bypass, the fidelity of those low-fidelity polymerases at these pause sites was also significantly decreased. Thus, if the translesion DNA synthesis of dGAP in vivo is catalyzed by a human Y-family DNA polymerase, e.g. hPolη, the process is certainly mutagenic. PMID:22324639

Parp1 activation in mouse embryonic fibroblasts promotes Pol β-dependent cellular hypersensitivity to alkylation damage

PubMed Central

Jelezcova, Elena; Trivedi, Ram N.; Wang, Xiao-hong; Tang, Jiang-bo; Brown, Ashley R.; Goellner, Eva M.; Schamus, Sandy; Fornsaglio, Jamie L.; Sobol, Robert W.

2010-01-01

Alkylating agents induce cell death in wild-type (WT) mouse embryonic fibroblasts (MEFs) by multiple mechanisms, including apoptosis, autophagy and necrosis. DNA polymerase β (Pol β) knockout (KO) MEFs are hypersensitive to the cytotoxic effect of alkylating agents, as compared to WT MEFs. To test the hypothesis that Parp1 is preferentially activated by methyl methanesulfonate (MMS) exposure of Pol β KO MEFs, we have examined the relationship between Pol β expression, Parp1 activation and cell survival following MMS exposure in a series of WT and Pol β deficient MEF cell lines. Consistent with our hypothesis, we observed elevated Parp1 activation in Pol β KO MEFs as compared to matched WT MEFs. Both the MMS-induced activation of Parp1 and the MMS-induced cytoxicity of Pol β KO MEFs are attenuated by pre-treatment with the Parp1/Parp2 inhibitor PJ34. Further, elevated Parp1 activation is observed following knockdown (KD) of endogenous Pol β, as compared to WT cells. Pol β KD MEFs are hypersensitive to MMS and both the MMS-induced hypersensitivity and Parp1 activation is prevented by pre-treatment with PJ34. In addition, the MMS-induced cellular sensitivity of Pol β KO MEFs is reversed when Parp1 is also deleted (Pol β/Parp1 double KO MEFs) and we observe no MMS sensitivity differential between Pol β/Parp1 double KO MEFs and those that express recombinant mouse Pol β. These studies suggest that Parp1 may function as a sensor of BER to initiate cell death when BER is aborted or fails. Parp1 may therefore function in BER as a tumor suppressor by initiating cell death and preventing the accumulation of cells with chromosomal damage due to a BER defect. PMID:20096707

Herpes Simplex Virus Processivity Factor UL42 Imparts Increased DNA-Binding Specificity to the Viral DNA Polymerase and Decreased Dissociation from Primer-Template without Reducing the Elongation Rate

PubMed Central

Weisshart, Klaus; Chow, Connie S.; Coen, Donald M.

1999-01-01

Herpes simplex virus DNA polymerase consists of a catalytic subunit, Pol, and a processivity subunit, UL42, that, unlike other established processivity factors, binds DNA directly. We used gel retardation and filter-binding assays to investigate how UL42 affects the polymerase-DNA interaction. The Pol/UL42 heterodimer bound more tightly to DNA in a primer-template configuration than to single-stranded DNA (ssDNA), while Pol alone bound more tightly to ssDNA than to DNA in a primer-template configuration. The affinity of Pol/UL42 for ssDNA was reduced severalfold relative to that of Pol, while the affinity of Pol/UL42 for primer-template DNA was increased ∼15-fold relative to that of Pol. The affinity of Pol/UL42 for circular double-stranded DNA (dsDNA) was reduced drastically relative to that of UL42, but the affinity of Pol/UL42 for short primer-templates was increased modestly relative to that of UL42. Pol/UL42 associated with primer-template DNA ∼2-fold faster than did Pol and dissociated ∼10-fold more slowly, resulting in a half-life of 2 h and a subnanomolar Kd. Despite such stable binding, rapid-quench analysis revealed that the rates of elongation of Pol/UL42 and Pol were essentially the same, ∼30 nucleotides/s. Taken together, these studies indicate that (i) Pol/UL42 is more likely than its subunits to associate with DNA in a primer-template configuration rather than nonspecifically to either ssDNA or dsDNA, and (ii) UL42 reduces the rate of dissociation from primer-template DNA but not the rate of elongation. Two models of polymerase-DNA interactions during replication that may explain these findings are presented. PMID:9847307

A switch between DNA polymerases δ and λ promotes error-free bypass of 8-oxo-G lesions

PubMed Central

Markkanen, Enni; Castrec, Benoît; Villani, Giuseppe; Hübscher, Ulrich

2012-01-01

7,8-Dihydro-8-oxoguanine (8-oxo-G) is a highly abundant and mutagenic lesion. Replicative DNA polymerases (pols) are slowed down at 8-oxo-G and insert both correct cytosine (C) and incorrect adenine (A) opposite 8-oxo-G, but they preferentially extend A:8-oxo-G mispairs. Nevertheless, 8-oxo-G bypass is fairly accurate in vivo. Thus, the question how correct bypass of 8-oxo-G lesions is accomplished despite the poor extension of C:8-oxo-G base pairs by replicative pols remains unanswered. Here we show that replicative pol δ pauses in front of 8-oxo-G and displays difficulties extending from correct C:8-oxo-G in contrast to extension from incorrect A:8-oxo-G. This leads to stalling of pol δ at 8-oxo-G after incorporation of correct C. This stalling at C:8-oxo-G can be overcome by a switch from pol δ to pols λ, β, or η, all of which are able to assist pol δ in 8-oxo-G bypass by translesion synthesis (TLS). Importantly, however, only pol λ selectively catalyzes the correct TLS past 8-oxo-G, whereas pols β and η show no selectivity and even preferentially enhance incorrect TLS. The selectivity of pol λ to promote the correct bypass depends on its N-terminal domain. Furthermore, pol λ−/− mouse embryonic fibroblast extracts display reduced 8-oxo-G TLS. Finally, the correct bypass of 8-oxo-G in gapped plasmids in mouse embryonic fibroblasts and HeLa cells is promoted in the presence of pol λ. Our findings suggest that even though 8-oxo-G is not a blocking lesion per se, correct replication over 8-oxo-G is promoted by a pol switch between pols δ and λ. PMID:23175785

Probing low-energy hyperbolic polaritons in van der Waals crystals with an electron microscope.

PubMed

Govyadinov, Alexander A; Konečná, Andrea; Chuvilin, Andrey; Vélez, Saül; Dolado, Irene; Nikitin, Alexey Y; Lopatin, Sergei; Casanova, Fèlix; Hueso, Luis E; Aizpurua, Javier; Hillenbrand, Rainer

2017-07-21

Van der Waals materials exhibit intriguing structural, electronic, and photonic properties. Electron energy loss spectroscopy within scanning transmission electron microscopy allows for nanoscale mapping of such properties. However, its detection is typically limited to energy losses in the eV range-too large for probing low-energy excitations such as phonons or mid-infrared plasmons. Here, we adapt a conventional instrument to probe energy loss down to 100 meV, and map phononic states in hexagonal boron nitride, a representative van der Waals material. The boron nitride spectra depend on the flake thickness and on the distance of the electron beam to the flake edges. To explain these observations, we developed a classical response theory that describes the interaction of fast electrons with (anisotropic) van der Waals slabs, revealing that the electron energy loss is dominated by excitation of hyperbolic phonon polaritons, and not of bulk phonons as often reported. Thus, our work is of fundamental importance for interpreting future low-energy loss spectra of van der Waals materials.Here the authors adapt a STEM-EELS system to probe energy loss down to 100 meV, and apply it to map phononic states in hexagonal boron nitride, revealing that the electron loss is dominated by hyperbolic phonon polaritons.

Freight advanced traveler information system : concept of operations.

DOT National Transportation Integrated Search

2012-08-01

This report describes a Concept of Operations (ConOps) for a Freight Advanced Traveler Information System (FRATIS). The ConOps describes the goals, functions, key concepts, user classes, high-level architecture, operational scenarios, operational pol...

Each Monomer of the Dimeric Accessory Protein for Human Mitochondrial DNA Polymerase Has a Distinct Role in Conferring Processivity*

PubMed Central

Lee, Young-Sam; Lee, Sujin; Demeler, Borries; Molineux, Ian J.; Johnson, Kenneth A.; Yin, Y. Whitney

2010-01-01

The accessory protein polymerase (pol) γB of the human mitochondrial DNA polymerase stimulates the synthetic activity of the catalytic subunit. pol γB functions by both accelerating the polymerization rate and enhancing polymerase-DNA interaction, thereby distinguishing itself from the accessory subunits of other DNA polymerases. The molecular basis for the unique functions of human pol γB lies in its dimeric structure, where the pol γB monomer proximal to pol γA in the holoenzyme strengthens the interaction with DNA, and the distal pol γB monomer accelerates the reaction rate. We further show that human pol γB exhibits a catalytic subunit- and substrate DNA-dependent dimerization. By duplicating the monomeric pol γB of lower eukaryotes, the dimeric mammalian proteins confer additional processivity to the holoenzyme polymerase. PMID:19858216

Zusammenarbeit aus Sicht eines outgesourcten Instandhalters

NASA Astrophysics Data System (ADS)

Grüßer, Stefan; Loeven, Heinz-Wilhelm

Dauerhafter Unternehmenserfolg ist nur mit einer fortschrittlichen Instandhaltung zu erzielen. Durch den enormen Kostendruck infolge der Globalisierung und die Innovationssprünge auf der technischen Seite wird auch die Frage nach der modernen Organisationsform für die Instandhaltung gestellt. Eine Möglichkeit der Kostenoptimierung ist das Outsourcing von Instandhaltungsleistungen. Hierbei ist es unerlässlich, dass sich die Mitarbeiter zum Dienstleister entwickeln. In diesem Beitrag wird die Entwicklung der InfraServ Knapsack von einer internen Instandhaltungsabteilung hin zu einem Industriellen Dienstleister beschrieben und Aspekte der Zusammenarbeit mit externen Kunden aus der Sicht des outgesourcten Instandhalters geschildert. Es werden die wichtigen Entwicklungsschritte zur Dienstleistungsorientierung der früheren Eigeninstandhaltung aufgezeigt. Dieser Beitrag ist nicht als "Königsweg“ zu verstehen, er soll vielmehr anhand der Erfahrungen einer outgesourcten Eigeninstandhaltung Anregungen für die Entwicklung der eigenen Instandhaltungsorganisation liefern.

Heterologous Expression of Der Homologs in an Escherichia coli der Mutant and Their Functional Complementation

PubMed Central

Choi, Eunsil; Kang, Nalae; Jeon, Young; Pai, Hyun-Sook

2016-01-01

ABSTRACT The unique Escherichia coli GTPase Der (double Era-like GTPase), which contains tandemly repeated GTP-binding domains, has been shown to play an essential role in 50S ribosomal subunit biogenesis. The depletion of Der results in the accumulation of precursors of 50S ribosomal subunits that are structurally unstable at low Mg2+ concentrations. Der homologs are ubiquitously found in eubacteria. Conversely, very few are conserved in eukaryotes, and none is conserved in archaea. In the present study, to verify their conserved role in bacterial 50S ribosomal subunit biogenesis, we cloned Der homologs from two gammaproteobacteria, Klebsiella pneumoniae and Salmonella enterica serovar Typhimurium; two pathogenic bacteria, Staphylococcus aureus and Neisseria gonorrhoeae; and the extremophile Deinococcus radiodurans and then evaluated whether they could functionally complement the E. coli der-null phenotype. Only K. pneumoniae and S. Typhimurium Der proteins enabled the E. coli der-null strain to grow under nonpermissive conditions. Sucrose density gradient experiments revealed that the expression of K. pneumoniae and S. Typhimurium Der proteins rescued the structural instability of 50S ribosomal subunits, which was caused by E. coli Der depletion. To determine what allows their complementation, we constructed Der chimeras. We found that only Der chimeras harboring both the linker and long C-terminal regions could reverse the growth defects of the der-null strain. Our findings suggest that ubiquitously conserved essential GTPase Der is involved in 50S ribosomal subunit biosynthesis in various bacteria and that the linker and C-terminal regions may participate in species-specific recognition or interaction with the 50S ribosomal subunit. IMPORTANCE In Escherichia coli, Der (double Era-like GTPase) is an essential GTPase that is important for the production of mature 50S ribosomal subunits. However, to date, its precise role in ribosome biogenesis has not been clarified. In this study, we used five Der homologs from gammaproteobacteria, pathogenic bacteria, and an extremophile to elucidate their conserved function in 50S ribosomal subunit biogenesis. Among them, Klebsiella pneumoniae and Salmonella enterica serovar Typhimurium Der homologs implicated the participation of Der in ribosome assembly in E. coli. Our results show that the linker and C-terminal regions of Der homologs are correlated with its functional complementation in E. coli der mutants, suggesting that they are involved in species-specific recognition or interaction with 50S ribosomal subunits. PMID:27297882

Alternative splicing at exon 2 results in the loss of the catalytic activity of mouse DNA polymerase iota in vitro.

PubMed

Kazachenko, Konstantin Y; Miropolskaya, Nataliya A; Gening, Leonid V; Tarantul, Vyacheslav Z; Makarova, Alena V

2017-02-01

Y-family DNA polymerase iota (Pol ι) possesses both DNA polymerase and dRP lyase activities and was suggested to be involved in DNA translesion synthesis and base excision repair in mammals. The 129 strain of mice and its derivatives have a natural nonsense codon mutation in the second exon of the Pol ι gene resulting in truncation of the Pol ι protein. These mice were widely used as a Pol ι-null model for in vivo studies of the Pol ι function. However whether 129-derived strains of mice are fully deficient in the Pol ι functions was a subject of discussion since Pol ι mRNA undergoes alternative splicing at exon 2. Here we report purification of mouse Pol ι lacking the region encoded by exon 2, which includes several conserved residues involved in catalysis. We show that the deletion abrogates both the DNA polymerase and dRP lyase activities of Pol ι in the presence of either Mg 2+ or Mn 2+ ions. Thus, 129-derived strains of mice express catalytically inactive alternatively spliced Pol ι variant, whose cellular functions, if any exist, remain to be established. Copyright © 2017 Elsevier B.V. All rights reserved.

Structure-based design and screening of inhibitors for an essential bacterial GTPase, Der.

PubMed

Hwang, Jihwan; Tseitin, Vladimir; Ramnarayan, Kal; Shenderovich, Mark D; Inouye, Masayori

2012-05-01

Der is an essential and widely conserved GTPase that assists assembly of a large ribosomal subunit in bacteria. Der associates specifically with the 50S subunit in a GTP-dependent manner and the cells depleted of Der accumulate the structurally unstable 50S subunit, which dissociates into an aberrant subunit at a lower Mg(2+) concentration. As Der is an essential and ubiquitous protein in bacteria, it may prove to be an ideal cellular target against which new antibiotics can be developed. In the present study, we describe our attempts to identify novel antibiotics specifically targeting Der GTPase. We performed the structure-based design of Der inhibitors using the X-ray crystal structure of Thermotoga maritima Der (TmDer). Virtual screening of commercially available chemical library retrieved 257 small molecules that potentially inhibit Der GTPase activity. These 257 chemicals were tested for their in vitro effects on TmDer GTPase and in vivo antibacterial activities. We identified three structurally diverse compounds, SBI-34462, -34566 and -34612, that are both biologically active against bacterial cells and putative enzymatic inhibitors of Der GTPase homologs. We also presented the possible interactions of each compound with the Der GTP-binding site to understand the mechanism of inhibition. Therefore, our lead compounds inhibiting Der GTPase provide scaffolds for the development of novel antibiotics against antibiotic-resistant pathogenic bacteria.

Polinsar Experiments of Multi-Mode X-Band Data Over South Area of China

NASA Astrophysics Data System (ADS)

Lu, L.; Yan, Q.; Duan, M.; Zhang, Y.

2012-08-01

This paper makes the polarimetric and polarimetric interferometric synthetic aperture radar (PolInSAR) experiments with the high-resolution X-band data acquired by Multi-mode airborne SAR system over an area around Linshui, south of China containing tropic vegetation and urban areas. Polarimetric analysis for typical tropic vegetations and man-made objects are presented, some polarimetric descriptors sensitive to vegetations and man-made objects are selected. Then, the PolInSAR information contained in the data is investigated, considering characteristics of the Multi-mode-XSAR dataset, a dual-baseline polarimetric interferometry method is proposed in this paper. The method both guarantees the high coherence on fully polarimetric data and combines the benefits of short and long baseline that helpful to the phase unwrapping and height sensitivity promotion. PolInSAR experiment results displayed demonstrates Multi-mode-XSAR datasets have intuitive capabilities for amount of application of land classification, objects detection and DSM mapping.

Classification of fully polarimetric F-SAR ( X / S ) airborne radar images using decomposition methods. (Polish Title: Klasyfikacja treści polarymetrycznych obrazów radarowych z wykorzystaniem metod dekompozycji na przykładzie systemu F-SAR ( X / S ))

NASA Astrophysics Data System (ADS)

Mleczko, M.

2014-12-01

Polarimetric SAR data is not widely used in practice, because it is not yet available operationally from the satellites. Currently we can distinguish two approaches in POL - In - SAR technology: alternating polarization imaging (Alt - POL) and fully polarimetric (QuadPol). The first represents a subset of another and is more operational, while the second is experimental because classification of this data requires polarimetric decomposition of scattering matrix in the first stage. In the literature decomposition process is divided in two types: the coherent and incoherent decomposition. In this paper the decomposition methods have been tested using data from the high resolution airborne F - SAR system. Results of classification have been interpreted in the context of the land cover mapping capabilities

Temperature requirements for initiation of RNA-dependent RNA polymerization.

PubMed

Yang, Hongyan; Gottlieb, Paul; Wei, Hui; Bamford, Dennis H; Makeyev, Eugene V

2003-09-30

To continue the molecular characterization of RNA-dependent RNA polymerases of dsRNA bacteriophages (Cystoviridae), we purified and biochemically characterized the wild-type (wt) and a temperature-sensitive (ts) point mutant of the polymerase subunit (Pol) from bacteriophage phi12. Interestingly, initiation by both wt and the ts phi12 Pol was notably more sensitive to increased temperatures than the elongation step, the absolute value of the nonpermissive temperature being lower for the ts enzyme. Experiments with the Pol subunit of related cystovirus phi6 revealed a similar differential sensitivity of the initiation and elongation steps. This is consistent with the previous result showing that de novo initiation by RdRp from dengue virus is inhibited at elevated temperatures, whereas the elongation phase is relatively thermostable. Overall, these data suggest that de novo RNA-dependent RNA synthesis in many viral systems includes a specialized thermolabile state of the RdRp initiation complex.

Development of a "First Principles" Water Potential with Flexible Monomers: Dimer Potential Energy Surface, VRT Spectrum, and Second Virial Coefficient.

PubMed

Babin, Volodymyr; Leforestier, Claude; Paesani, Francesco

2013-12-10

The development of a "first principles" water potential with flexible monomers (MB-pol) for molecular simulations of water systems from gas to condensed phases is described. MB-pol is built upon the many-body expansion of the intermolecular interactions, and the specific focus of this study is on the two-body term (V2B) representing the full-dimensional intermolecular part of the water dimer potential energy surface. V2B is constructed by fitting 40,000 dimer energies calculated at the CCSD(T)/CBS level of theory and imposing the correct asymptotic behavior at long-range as predicted from "first principles". The comparison of the calculated vibration-rotation tunneling (VRT) spectrum and second virial coefficient with the corresponding experimental results demonstrates the accuracy of the MB-pol dimer potential energy surface.

SOUTH POL: Revealing the Polarized Southern Sky

NASA Astrophysics Data System (ADS)

Magalhaes, Antonio Mario Mario; Ramírez, Edgar; Ribeiro, Nadili; Seriacopi, Daiane; Rubinho, Marcelo; Ferrari, Tiberio; Rodrigues, Claudia; Schoenell, William; Herpich, Fabio; Pereyra, Antonio

2018-01-01

SOUTH POL will be a survey of the Southern sky in optical polarized light. It will use a newly built polarimeter for T80-S, an 84 cm robotic telescope installed at Cerro Tololo (CTIO), Chile. It will initially cover the sky South of declination -15 deg with a polarimetric accuracy < 0.1% at V~14-15. The telescope and camera combination covers a field of about 2.0 square degrees.SOUTH POL will impact areas such as Cosmology, Extragalactic Astronomy, Interstellar Medium of the Galaxy and Magellanic Clouds, Star Formation, Stellar Envelopes, Stellar Explosions and Solar System.The polarimeter has just been commissioned in mid-November, 2017. The data reduction pipeline has already been built. We will describe the instrument and the data reduction, as well as a few of the science cases. The survey is expected to begin midway through the 1st semester of 2018. Both catalog data and raw images will be made available.

Semi-empirical correlation for binary interaction parameters of the Peng-Robinson equation of state with the van der Waals mixing rules for the prediction of high-pressure vapor-liquid equilibrium.

PubMed

Fateen, Seif-Eddeen K; Khalil, Menna M; Elnabawy, Ahmed O

2013-03-01

Peng-Robinson equation of state is widely used with the classical van der Waals mixing rules to predict vapor liquid equilibria for systems containing hydrocarbons and related compounds. This model requires good values of the binary interaction parameter kij . In this work, we developed a semi-empirical correlation for kij partly based on the Huron-Vidal mixing rules. We obtained values for the adjustable parameters of the developed formula for over 60 binary systems and over 10 categories of components. The predictions of the new equation system were slightly better than the constant-kij model in most cases, except for 10 systems whose predictions were considerably improved with the new correlation.

Kants Theorie der Sonne: Physikgeschichte

NASA Astrophysics Data System (ADS)

Jacobi, Manfred

2005-01-01

Im Rahmen seiner Kosmogonie entwickelte der junge Immanuel Kant eine Theorie der Sonne. Sie ist ein einzigartiges Zeugnis seiner intuitiven Vorstellungskraft und beweist auch die Leistungsfähigkeit der damaligen, vorwiegend von Newton geprägten Weltsicht. Entstehung, Aufbau und Dynamik der Sonne werden in Kants Theorie ebenso erklärt wie etwa das Phänomen der Sonnenflecken.

Combat Casualty Hand Burns: Evaluating Impairment and Disability during Recovery

DTIC Science & Technology

2008-06-01

impairment guidelines would correlate with disability as mea- sured by the DASH. However, a study by Mink van der Molen et al. found only a weak correlation (r...Mink van der Molen AB, Ettema AM, Hovius SER. Outcome of hand trauma: the hand injury severity scoring system (HISS) and subsequent impairment and...0.38) between AMA and DASH scores at six months after hand trauma.16 In another study, van Oosterom et al. reported no statistically significant

The Unknown Generals - German Corps Commanders in World War 2.

DTIC Science & Technology

1988-06-03

Rudolf Schnundt: 1.10.42-29.10.44. (Daily Reports of *the Chief of the Army Personnel Office General of Infantry Rudolf Sch undt: October 1, 1942 to...loan. i German officer efficiency reports are discussed by Rudolf S.Hofmann in "German Efficiency Report System" another Historical Division study. The...General der Infanterie Rudolf Schmundt, and General der Infanterie Wilhelm Burgdorf were three of these men. 63 Wilhelm Keitel served as Chief of Staff

Funkmesstechnik

NASA Astrophysics Data System (ADS)

Plaßmann, Wilfried

Ein Hauptgebiet der Funkmesstechnik ist durch den Begriff RADAR (radio detection and ranging gekennzeichnet. Bei diesem Verfahren werden impulsförmige elektromagnetische Wellen von einer Antenne ausgesendet und an Körpern oder Stoffverteilungen (Wolken) reflektiert. Die Sendeantenne wird auf Empfang umgeschaltet, und anhand des Echos sind Rückschlüsse auf die Lage und die Beschaffenheit der Körper oder der Stoffverteilungen möglich. Angewendet wird die Radartechnik bei der Kontrolle und der Sicherung des Land-, Wasser- und Flugverkehrs, in der Meteorologie zur Wetterprognose, in der Astrologie und im militärischen Bereich.

Communication: THz absorption spectrum of the CO2-H2O complex: observation and assignment of intermolecular van der Waals vibrations.

PubMed

Andersen, J; Heimdal, J; Mahler, D W; Nelander, B; Larsen, R Wugt

2014-03-07

Terahertz absorption spectra have been recorded for the weakly bound CO2-H2O complex embedded in cryogenic neon matrices at 2.8 K. The three high-frequency van der Waals vibrational transitions associated with out-of-plane wagging, in-plane rocking, and torsional motion of the isotopic H2O subunit have been assigned and provide crucial observables for benchmark theoretical descriptions of this systems' flat intermolecular potential energy surface. A (semi)-empirical value for the zero-point energy of 273 ± 15 cm(-1) from the class of intermolecular van der Waals vibrations is proposed and the combination with high-level quantum chemical calculations provides a value of 726 ± 15 cm(-1) for the dissociation energy D0.

Spatiotemporal recruitment of human DNA polymerase delta to sites of UV damage

PubMed Central

Chea, Jennifer; Zhang, Sufang; Zhao, Hong; Zhang, Zhongtao; Lee, Ernest Y.C.; Darzynkiewicz, Zbigniew; Lee, Marietta Y.W.T.

2012-01-01

Human DNA polymerase δ (Pol δ) is involved in various DNA damage responses in addition to its central role in DNA replication. The Pol δ4 holoenzyme consists of four subunits, p125, p50, p68 and p12. It has been established that the p12 subunit is rapidly degraded in response to DNA damage by UV leading to the in vivo conversion of Pol δ4 to Pol δ3, a trimeric form lacking the p12 subunit. We provide the first analysis of the time-dependent recruitment of the individual Pol δ subunits to sites of DNA damage produced by UV irradiation through 5 μm polycarbonate filters by immunofluorescence microscopy and laser scanning cytometry (LSC). Quantitative analysis demonstrates that the recruitments of the three large subunits was near complete by 2 h and did not change significantly up to 4 h after UV exposure. However, the recruitment of p12 was incomplete even at 4 h, with about 70% of the Pol δ lacking the p12 subunit. ChIP analysis of Pol δ after global UV irradiation further demonstrates that only p125, p50 and p68 were present. Thus, Pol δ3 is the predominant form of Pol δ at sites of UV damage as a result of p12 degradation. Using LSC, we have further confirmed that Pol δ was recruited to CPD damage sites in all phases of the cell cycle. Collectively, our results show that Pol δ at the DNA damage site is the Pol δ trimer lacking p12 regardless of the cell cycle phase. PMID:22801543

Mechanism of Error-Free DNA Replication Past Lucidin-Derived DNA Damage by Human DNA Polymerase κ.

PubMed

Yockey, Oliver P; Jha, Vikash; Ghodke, Pratibha P; Xu, Tianzuo; Xu, Wenyan; Ling, Hong; Pradeepkumar, P I; Zhao, Linlin

2017-11-20

DNA damage impinges on genetic information flow and has significant implications in human disease and aging. Lucidin-3-O-primeveroside (LuP) is an anthraquinone derivative present in madder root, which has been used as a coloring agent and food additive. LuP can be metabolically converted to genotoxic compound lucidin, which subsequently forms lucidin-specific N 2 -2'-deoxyguanosine (N 2 -dG) and N 6 -2'-deoxyadenosine (N 6 -dA) DNA adducts. Lucidin is mutagenic and carcinogenic in rodents but has low carcinogenic risks in humans. To understand the molecular mechanism of low carcinogenicity of lucidin in humans, we performed DNA replication assays using site-specifically modified oligodeoxynucleotides containing a structural analogue (LdG) of lucidin-N 2 -dG DNA adduct and determined the crystal structures of DNA polymerase (pol) κ in complex with LdG-bearing DNA and an incoming nucleotide. We examined four human pols (pol η, pol ι, pol κ, and Rev1) in their efficiency and accuracy during DNA replication with LdG; these pols are key players in translesion DNA synthesis. Our results demonstrate that pol κ efficiently and accurately replicates past the LdG adduct, whereas DNA replication by pol η, pol ι is compromised to different extents. Rev1 retains its ability to incorporate dCTP opposite the lesion albeit with decreased efficiency. Two ternary crystal structures of pol κ illustrate that the LdG adduct is accommodated by pol κ at the enzyme active site during insertion and postlesion-extension steps. The unique open active site of pol κ allows the adducted DNA to adopt a standard B-form for accurate DNA replication. Collectively, these biochemical and structural data provide mechanistic insights into the low carcinogenic risk of lucidin in humans.

Specific amino acid residues in the beta sliding clamp establish a DNA polymerase usage hierarchy in Escherichia coli.

PubMed

Sutton, Mark D; Duzen, Jill M

2006-03-07

Escherichia coli dnaN159 strains encode a mutant form of the beta sliding clamp (beta159), causing them to display altered DNA polymerase (pol) usage. In order to better understand mechanisms of pol selection/switching in E. coli, we have further characterized pol usage in the dnaN159 strain. The dnaN159 allele contains two amino acid substitutions: G66E (glycine-66 to glutamic acid) and G174A (glycine-174 to alanine). Our results indicated that the G174A substitution impaired interaction of the beta clamp with the alpha catalytic subunit of pol III. In light of this finding, we designed two additional dnaN alleles. One of these dnaN alleles contained a G174A substitution (beta-G174A), while the other contained D173A, G174A and H175A substitutions (beta-173-175). Examination of strains bearing these different dnaN alleles indicated that each conferred a distinct UV sensitive phenotype that was dependent upon a unique combination of Delta polB (pol II), Delta dinB (pol IV) and/or Delta umuDC (pol V) alleles. Taken together, these findings indicate that mutations in the beta clamp differentially affect the functions of these three pols, and suggest that pol II, pol IV and pol V are capable of influencing each others' abilities to gain access to the replication fork. These findings are discussed in terms of a model whereby amino acid residues in the vicinity of those mutated in beta159 (G66 and G174) help to define a DNA polymerase usage hierarchy in E. coli following UV irradiation.

Gesammelte Werke / Collected Works

NASA Astrophysics Data System (ADS)

Schwarzschild, Karl; Voigt, Hans-Heinrich

Der bekannte Astronom Karl Schwarzschild (1873-1916) gilt als der Begründer der Astrophysik und als hervorragender Forscher mit einer erstaunlichen Bandbreite seiner Interessen. Arbeiten zur Himmelsmechanik, Elektrodynamik und Relativitätstheorie weisen ihn als vorzüglichen Mathematiker und Physiker auf der Höhe seiner Zeit aus. Untersuchungen zur Photographischen Photometrie, Optik und Spektroskopie zeigen den versierten Beobachter, der sein Meßinstrumentarium beherrscht, und schließlich arbeitete Schwarzschild als Astrophysiker an Sternatmosphären, Kometen, Struktur und Dynamik von Sternsystemen. Die in seinem kurzen Leben entstandene Fülle an wissenschaftlichen Arbeiten ist in drei Bänden der Gesamtausgabe gesammelt, ergänzt durch biographisches Material, Annotationen von Fachleuten und einen Essay des Nobelpreisträgers S. Chandrasekhar. The well-known astronomer Karl Schwarzschild (1873-1916) is regarded as the founder of astrophysics and as an exceptionally talented researcher whose interests spanned a remarkably broad spectrum. His work on celestial mechanics, electrodynamics, and relativity theory demonstrates his great abilities as a mathematician and physicist who significantly influenced the science of his times. His investigations of photographic photometry, optics, and spectroscopy display his strengths as an observer who knew his instruments. But above all Schwarzschild pursued questions of astrophysics, addressing in particular stellar atmospheres, comets, and the structure and dynamics of stellar systems. The host of scientific works that he authored in his short life is now collected in the form of this three-volume complete works; it is supplemented by biographical material, notes from some of todays experts, and an essay by the Nobel Laureate S. Chandrasekhar.

In silico structural analysis of group 3, 6 and 9 allergens from Dermatophagoides farinae.

PubMed

Teng, Feixiang; Yu, Lili; Bian, Yonghua; Sun, Jinxia; Wu, Juansong; Ling, Cunbao; Yang, Li; Wang, Yungang; Cui, Yubao

2015-05-01

Dermatophagoides farinae (Hughes; Acari: Pyroglyphidae) are the predominant source of dust mite allergens, which provoke allergic diseases, such as rhinitis, asthma and eczema. Of the 30 allergen groups produced by D. farinae, the Der f 3, Der f 6 and Der f 9 allergens are all trypsin‑associated proteins, however little else is currently known about them. The present study used in silico tools to compare the amino acid sequences, and predict the secondary and tertiary structures of Der f 3, Der f 6 and Der f 9 allergens. Protein sequence alignment detected ~46% identity between Der f 3, Der f 6 and Der f 9. Furthermore, each protein was shown to contain three active sites and two highly conserved trypsin functional domains. Predictions of the secondary and tertiary structure identified α‑helices, β‑sheets and random coils. The active sites of the three proteins appeared to fold onto each other in a three‑dimensional model, constituting the active site of the enzyme. Epitope analysis demonstrated that Der f 3, Der f 6 and Der f 9 have 4‑5 potential epitopes located in random coils, and the epitope sequences of Der f 3, Der f 6 and Der f 9 were shown to overlap in two domains (at amino acids 83‑87 and 179‑180); however the residues in these two domains were not identical. The present study aimed to conduct a biochemical and genetic analysis of these three allergens, and to potentially contribute to the development of vaccines for allergen‑specific immunotherapy.

Finite-Size Effects on the Behavior of the Susceptibility in van der Waals Films Bounded by Strongly Absorbing Substrates

NASA Technical Reports Server (NTRS)

Dantchev, Daniel; Rudnick, Joseph; Barmatz, M.

2007-01-01

We study critical point finite-size effects in the case of the susceptibility of a film in which interactions are characterized by a van der Waals-type power law tail. The geometry is appropriate to a slab-like system with two bounding surfaces. Boundary conditions are consistent with surfaces that both prefer the same phase in the low temperature, or broken symmetry, state. We take into account both interactions within the system and interactions between the constituents of the system and the material surrounding it. Specific predictions are made with respect to the behavior of 3He and 4He films in the vicinity of their respective liquid-vapor critical points.

Anti-Armor Defense Data Study (A2D2). Phase 2. Volume 4. US Anti-Tank Defense at Krinkelt-Rocherath, Belgium (December, 1944)

DTIC Science & Technology

1991-02-15

Geschicbte der Stammdivision der Waffen -SS, Band V: 194 -1945. Osnabruck: Munln-Verlag, 1982. (Includes translation) (Stuttgart] 105 Weidinger, Otto, ed...1960. C -68 Weidinger, Otto. Division Das Reich. Der Weg der 2.SS Panzer-Division "Das Reich". Die Geschichte der Stammdivision der Waffen -SS, Band

Ferromagnetic mass fixed on a spring and subjected to an electromagnet powered by self-sustained oscillators

NASA Astrophysics Data System (ADS)

Abobda, L. T.; Woafo, P.

2014-12-01

The study of a ferromagnetic mass, fixed on a spring and subjected to an electromagnet powered by a Van der Pol (VDP) oscillator and by a Hindmarsh-Rose (HR) oscillator is performed, to serve as an electromechanical devices, but also to mimic the action of a natural pacemaker and nerves on a cardiac assist device or artificial heart. The excitation with the VDP oscillator shows in the mechanical part the transition from harmonic, periodic, biperiodic up to bursting oscillations, high displacement without pull-in instability in the free dynamics regime. Under DC plus square wave excitation, there is a coexistence of the bursting oscillations of the free dynamics and the one of the modulated dynamics. Considering the action of a HR oscillator, it is found transition from spikes, bursting oscillations, relaxation spikes, multiperiodic and sinusoidal oscillations under DC or DC plus square wave excitation. These electrical behaviors are transferred to the mechanical part which can then adopt spiking or bursting dynamics as the HR oscillator. For this electromechanical model, the VDP oscillator is more efficient than the HR oscillator to induce pulsatile pumping function with higher amplitude and to react to external influences without pull-in.

Functional diversification of maize RNA polymerase IV and V subtypes via alternative catalytic subunits

PubMed Central

Haag, Jeremy R.; Brower-Toland, Brent; Krieger, Elysia K.; Sidorenko, Lyudmila; Nicora, Carrie D.; Norbeck, Angela D.; Irsigler, Andre; LaRue, Huachun; Brzeski, Jan; McGinnis, Karen; Ivashuta, Sergey; Pasa-Tolic, Ljiljana; Chandler, Vicki L.; Pikaard, Craig S.

2014-01-01

Summary Unlike nuclear multisubunit RNA polymerases I, II and III, whose subunit compositions are conserved throughout eukaryotes, plant RNA Polymerases IV and V are non-essential, Pol II-related enzymes whose subunit compositions are still evolving. Whereas Arabidopsis Pols IV and V differ from Pol II in four or five of their twelve subunits, respectively, and differ from one another in three subunits, proteomic analyses show that maize Pols IV and V differ from Pol II in six subunits, but differ from each other only in their largest subunits. Use of alternative catalytic second-subunits, which are non-redundant for development and paramutation, yields at least two subtypes of Pol IV, and three subtypes of Pol V in maize. Pol IV/V associations with MOP1, RMR1, AGO121, Zm_DRD1/CHR127, SHH2a and SHH2b extend parallels between paramutation in maize and the RNA-directed DNA methylation pathway in Arabidopsis. PMID:25284785

DNA polymerase η modulates replication fork progression and DNA damage responses in platinum-treated human cells

NASA Astrophysics Data System (ADS)

Sokol, Anna M.; Cruet-Hennequart, Séverine; Pasero, Philippe; Carty, Michael P.

2013-11-01

Human cells lacking DNA polymerase η (polη) are sensitive to platinum-based cancer chemotherapeutic agents. Using DNA combing to directly investigate the role of polη in bypass of platinum-induced DNA lesions in vivo, we demonstrate that nascent DNA strands are up to 39% shorter in human cells lacking polη than in cells expressing polη. This provides the first direct evidence that polη modulates replication fork progression in vivo following cisplatin and carboplatin treatment. Severe replication inhibition in individual platinum-treated polη-deficient cells correlates with enhanced phosphorylation of the RPA2 subunit of replication protein A on serines 4 and 8, as determined using EdU labelling and immunofluorescence, consistent with formation of DNA strand breaks at arrested forks in the absence of polη. Polη-mediated bypass of platinum-induced DNA lesions may therefore represent one mechanism by which cancer cells can tolerate platinum-based chemotherapy.

Zu einer inhaltsorientierten Theorie des Lernens und Lehrens der biologischen Evolution

NASA Astrophysics Data System (ADS)

Wallin, Anita

Der Zweck dieser Studie (zwecks Überblick siehe dazu Abb. 9.1) war zu untersuchen, wie die Schüler der Sekundarstufe II ein Verständnis von der Theorie der biologischen Evolution entwickeln. Vom Ausgangspunkt "Vorurteile der Schüler“ ausgehend wurden Unterrichtssequenzen entwickelt und drei verschiedene Lernexperimente in einem zyklischen Prozess durchgeführt. Das Wissen der Schüler wurde vor, während und nach den Unterrichtssequenzen mit Hilfe von schriftlichen Tests, Interviews und Diskussionsrunden in kleinen Gruppen abgefragt. Etwa 80 % der Schüler hatten vor dem Unterricht alternative Vorstellungen von Evolution, und in dem Nachfolgetest erreichten circa 75 % ein wissenschaftliches Niveau. Die Argumentation der Schüler in den verschiedenen Tests wurde sorgfältig unter Rücksichtnahme auf Vorurteile, der konzeptionellen Struktur der Theorie der Evolution und den Zielen des Unterrichts analysiert. Daraus konnten Einsichten in solche Anforderungen an Lehren und Lernen gewonnen werden, die Herausforderungen an Schüler und Lehrer darstellen, wenn sie anfangen, evolutionäre Biologie zu lernen oder zu lehren. Ein wichtiges Ergebnis war, dass das Verständnis existierender Variation in einer Population der Schlüssel zum Verständnis von natürlicher Selektion ist. Die Ergebnisse sind in einer inhaltsorientierten Theorie zusammengefasst, welche aus drei verschiedenen Aspekten besteht: 1) den inhaltsspezifischen Aspekten, die einzigartig für jedes wissenschaftliche Feld sind; 2) den Aspekten, die die Natur der Wissenschaft betreffen; und 3) den allgemeinen Aspekten. Diese Theorie kann in neuen Experimenten getestet und weiter entwickelt werden.

Regulation of TFIIIB during F9 cell differentiation.

PubMed

Athineos, Dimitris; Marshall, Lynne; White, Robert J

2010-03-12

Differentiation of F9 embryonal carcinoma (EC) cells into parietal endoderm (PE) provides a tractable model system for studying molecular events during early and inaccessible stages of murine development. PE formation is accompanied by extensive changes in gene expression both in vivo and in culture. One of the most dramatic is the ~10-fold decrease in transcriptional output by RNA polymerase (pol) III. This has been attributed to changes in activity of TFIIIB, a factor that is necessary and sufficient to recruit pol III to promoters. The goal of this study was to identify molecular changes that can account for the low activity of TFIIIB following F9 cell differentiation. Three essential subunits of TFIIIB decrease in abundance as F9 cells differentiate; these are Brf1 and Bdp1, which are pol III-specific, and TBP, which is also used by pols I and II. The decreased levels of Brf1 and Bdp1 proteins can be explained by reduced expression of the corresponding mRNAs. However, this is not the case for TBP, which is regulated post-transcriptionally. In proliferating cells, pol III transcription is stimulated by the proto-oncogene product c-Myc and the mitogen-activated protein kinase Erk, both of which bind to TFIIIB. However, c-Myc levels fall during differentiation and Erk becomes inactive through dephosphorylation. The diminished abundance of TFIIIB is therefore likely to be compounded by changes to these positive regulators that are required for its full activity. In addition, PE cells have elevated levels of the retinoblastoma protein RB, which is known to bind and repress TFIIIB. The low activity of TFIIIB in PE can be attributed to a combination of changes, any one of which could be sufficient to inhibit pol III transcription. Declining levels of essential TFIIIB subunits and of activators that are required for maximal TFIIIB activity are accompanied by an increase in a potent repressor of TFIIIB. These events provide fail-safe guarantees to ensure that pol III output is appropriate to the diminished metabolic requirements of terminally differentiated cells.

Optimizing Power–Frequency Droop Characteristics of Distributed Energy Resources

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

Guggilam, Swaroop S.; Zhao, Changhong; Dall Anese, Emiliano

This paper outlines a procedure to design power-frequency droop slopes for distributed energy resources (DERs) installed in distribution networks to optimally participate in primary frequency response. In particular, the droop slopes are engineered such that DERs respond in proportion to their power ratings and they are not unfairly penalized in power provisioning based on their location in the distribution network. The main contribution of our approach is that a guaranteed level of frequency regulation can be guaranteed at the feeder head, while ensuring that the outputs of individual DERs conform to some well-defined notion of fairness. The approach we adoptmore » leverages an optimization-based perspective and suitable linearizations of the power-flow equations to embed notions of fairness and information regarding the physics of the power flows within the distribution network into the droop slopes. Time-domain simulations from a differential algebraic equation model of the 39-bus New England test-case system augmented with three instances of the IEEE 37-node distribution-network with frequency-sensitive DERs are provided to validate our approach.« less

In vivo evidence for translesion synthesis by the replicative DNA polymerase δ

PubMed Central

Hirota, Kouji; Tsuda, Masataka; Mohiuddin; Tsurimoto, Toshiki; Cohen, Isadora S.; Livneh, Zvi; Kobayashi, Kaori; Narita, Takeo; Nishihara, Kana; Murai, Junko; Iwai, Shigenori; Guilbaud, Guillaume; Sale, Julian E.; Takeda, Shunichi

2016-01-01

The intolerance of DNA polymerase δ (Polδ) to incorrect base pairing contributes to its extremely high accuracy during replication, but is believed to inhibit translesion synthesis (TLS). However, chicken DT40 cells lacking the POLD3 subunit of Polδ are deficient in TLS. Previous genetic and biochemical analysis showed that POLD3 may promote lesion bypass by Polδ itself independently of the translesion polymerase Polζ of which POLD3 is also a subunit. To test this hypothesis, we have inactivated Polδ proofreading in pold3 cells. This significantly restored TLS in pold3 mutants, enhancing dA incorporation opposite abasic sites. Purified proofreading-deficient human Polδ holoenzyme performs TLS of abasic sites in vitro much more efficiently than the wild type enzyme, with over 90% of TLS events resulting in dA incorporation. Furthermore, proofreading deficiency enhances the capability of Polδ to continue DNA synthesis over UV lesions both in vivo and in vitro. These data support Polδ contributing to TLS in vivo and suggest that the mutagenesis resulting from loss of Polδ proofreading activity may in part be explained by enhanced lesion bypass. PMID:27185888

RNA Pol IV and V in Gene Silencing: Rebel Polymerases Evolving Away From Pol II’s Rules

PubMed Central

Zhou, Ming; Law, Julie A.

2015-01-01

Noncoding RNAs regulate gene expression at both the transcriptional and post-transcriptional levels, and play critical roles in development, imprinting and the maintenance of genome integrity in eukaryotic organisms [1–3]. Therefore, it is important to understand how the production of such RNAs are controlled. In addition to the three canonical DNA dependent RNA polymerases (Pol) Pol I, II and III, two non-redundant plant-specific RNA polymerases, Pol IV and Pol V, have been identified and shown to generate noncoding RNAs that are required for transcriptional gene silencing via the RNA-directed DNA methylation (RdDM) pathway. Thus, somewhat paradoxically, transcription is required for gene silencing. This paradox extends beyond plants, as silencing pathways in yeast, fungi, flies, worms, and mammals also require transcriptional machinery [4,5]. As plants have evolved specialized RNA polymerases to carry out gene silencing in a manner that is separate from the essential roles of Pol II, their characterization offers unique insight into how RNA polymerases facilitate gene silencing. In this review, we focus on the mechanisms of Pol IV and Pol V function, including their compositions, their transcripts, and their modes of recruitment to chromatin. PMID:26344361

Human PrimPol activity is enhanced by RPA.

PubMed

Martínez-Jiménez, María I; Lahera, Antonio; Blanco, Luis

2017-04-10

Human PrimPol is a primase belonging to the AEP superfamily with the unique ability to synthesize DNA primers de novo, and a non-processive DNA polymerase able to bypass certain DNA lesions. PrimPol facilitates both mitochondrial and nuclear replication fork progression either acting as a conventional TLS polymerase, or repriming downstream of blocking lesions. In vivo assays have shown that PrimPol is rapidly recruited to sites of DNA damage by interaction with the human replication protein A (RPA). In agreement with previous findings, we show here that the higher affinity of RPA for ssDNA inhibits PrimPol activities in short ssDNA templates. In contrast, once the amount of ssDNA increases up to a length in which both proteins can simultaneously bind ssDNA, as expected during replicative stress conditions, PrimPol and RPA functionally interact, and their binding capacities are mutually enhanced. When using M13 ssDNA as template, RPA stimulated both the primase and polymerase activities of PrimPol, either alone or in synergy with Polε. These new findings supports the existence of a functional PrimPol/RPA association that allows repriming at the exposed ssDNA regions formed in the leading strand upon replicase stalling.

Transplantate und Implantate im Mittelohrbereich - Teil 1 (Stand 2002)

NASA Astrophysics Data System (ADS)

Kempf, Hans-Georg; Lenarz, Thomas; Eckert, Karl-Ludwig

In Deutschland leben ungefähr 12 Millionen Menschen, die an einer ein- oder beidseitigen Schwerhörigkeit leiden. Diese kann angeboren oder im Laufe des Lebens erworben sein. Klinisch und therapeutisch wichtig ist die Unterscheidung, ob die Ursache der Schwerhörigkeit im Bereich des Mittelohres, d. h. der Schallübertragung, oder im Bereich des Innenohres, der Hörnerven und der zentralen Hörbahnabschnitte, d. h. der Schallempfindung, liegt. 2,5 Millionen Schwerhörige haben dabei das Problem der Schallübertragung, d.h. die Störung liegt im Mittelohrbereich, und hier kann man in der Regel mit operativen, mikrochirurgisch durchgeführten Massnahmen helfen [1, 2]. Im Vordergrund steht als Ursache hier die chronische Mittelohrentzündung, die sich als Perforation des Trommelfells, als Defekt oder Unterbrechung der Gehörknöchelchen oder auch als Cholesteatom, einer sogenannte Knocheneiterung äussern kann [3]. Therapeutisch und damit als Prinzip der operativen Hörverbesserung steht primär der Verschluss des Trommelfells oder eine Rekonstruktion der Gehörknöchelchen an.

Polμ tumor variants decrease the efficiency and accuracy of NHEJ

PubMed Central

Sastre-Moreno, Guillermo; Pryor, John M.; Díaz-Talavera, Alberto; Ruiz, José F.; Ramsden, Dale A.

2017-01-01

Abstract The non homologous end-joining (NHEJ) pathway of double-strand break (DSB) repair often requires DNA synthesis to fill the gaps generated upon alignment of the broken ends, a complex task performed in human cells by two specialized DNA polymerases, Polλ and Polμ. It is now well established that Polμ is the one adapted to repair DSBs with non-complementary ends, the most challenging scenario, although the structural basis and physiological implications of this adaptation are not fully understood. Here, we demonstrate that two human Polμ point mutations, G174S and R175H, previously identified in two different tumor samples and affecting two adjacent residues, limit the efficiency of accurate NHEJ by Polμ in vitro and in vivo. Moreover, we show that this limitation is the consequence of a decreased template dependency during NHEJ, which renders the error-rate of the mutants higher due to the ability of Polμ to randomly incorporate nucleotides at DSBs. These results highlight the relevance of the 8 kDa domain of Polμ for accurate and efficient NHEJ, but also its contribution to the error-prone behavior of Polμ at 2-nt gaps. This work provides the first demonstration that mutations affecting Polμ identified in tumors can alter the efficiency and fidelity of NHEJ. PMID:28973441

Organizational differences between cytoplasmic male sterile and male fertile Brassica mitochondrial genomes are confined to a single transposed locus.

PubMed Central

L'Homme, Y; Brown, G G

1993-01-01

Comparison of the physical maps of male fertile (cam) and male sterile (pol) mitochondrial genomes of Brassica napus indicates that structural differences between the two mtDNAs are confined to a region immediately upstream of the atp6 gene. Relative to cam mtDNA, pol mtDNA possesses a 4.5 kb segment at this locus that includes a chimeric gene that is cotranscribed with atp6 and lacks an approximately 1kb region located upstream of the cam atp6 gene. The 4.5 kb pol segment is present and similarly organized in the mitochondrial genome of the common nap B.napus cytoplasm; however, the nap and pol DNA regions flanking this segment are different and the nap sequences are not expressed. The 4.5 kb CMS-associated pol segment has thus apparently undergone transposition during the evolution of the nap and pol cytoplasms and has been lost in the cam genome subsequent to the pol-cam divergence. This 4.5 kb segment comprises the single DNA region that is expressed differently in fertile, pol CMS and fertility restored pol cytoplasm plants. The finding that this locus is part of the single mtDNA region organized differently in the fertile and male sterile mitochondrial genomes provides strong support for the view that it specifies the pol CMS trait. Images PMID:8388101

Arabidopsis RNA Polymerases IV and V Are Required To Establish H3K9 Methylation, but Not Cytosine Methylation, on Geminivirus Chromatin

PubMed Central

Jackel, Jamie N.; Storer, Jessica M.; Coursey, Tami

2016-01-01

ABSTRACT In plants, RNA-directed DNA methylation (RdDM) employs small RNAs to target enzymes that methylate cytosine residues. Cytosine methylation and dimethylation of histone 3 lysine 9 (H3K9me2) are often linked. Together they condition an epigenetic defense that results in chromatin compaction and transcriptional silencing of transposons and viral chromatin. Canonical RdDM (Pol IV-RdDM), involving RNA polymerases IV and V (Pol IV and Pol V), was believed to be necessary to establish cytosine methylation, which in turn could recruit H3K9 methyltransferases. However, recent studies have revealed that a pathway involving Pol II and RNA-dependent RNA polymerase 6 (RDR6) (RDR6-RdDM) is likely responsible for establishing cytosine methylation at naive loci, while Pol IV-RdDM acts to reinforce and maintain it. We used the geminivirus Beet curly top virus (BCTV) as a model to examine the roles of Pol IV and Pol V in establishing repressive viral chromatin methylation. As geminivirus chromatin is formed de novo in infected cells, these viruses are unique models for processes involved in the establishment of epigenetic marks. We confirm that Pol IV and Pol V are not needed to establish viral DNA methylation but are essential for its amplification. Remarkably, however, both Pol IV and Pol V are required for deposition of H3K9me2 on viral chromatin. Our findings suggest that cytosine methylation alone is not sufficient to trigger de novo deposition of H3K9me2 and further that Pol IV-RdDM is responsible for recruiting H3K9 methyltransferases to viral chromatin. IMPORTANCE In plants, RNA-directed DNA methylation (RdDM) uses small RNAs to target cytosine methylation, which is often linked to H3K9me2. These epigenetic marks silence transposable elements and DNA virus genomes, but how they are established is not well understood. Canonical RdDM, involving Pol IV and Pol V, was thought to establish cytosine methylation that in turn could recruit H3K9 methyltransferases, but recent studies compel a reevaluation of this view. We used BCTV to investigate the roles of Pol IV and Pol V in chromatin methylation. We found that both are needed to amplify, but not to establish, DNA methylation. However, both are required for deposition of H3K9me2. Our findings suggest that cytosine methylation is not sufficient to recruit H3K9 methyltransferases to naive viral chromatin and further that Pol IV-RdDM is responsible. PMID:27279611

Arabidopsis RNA Polymerases IV and V Are Required To Establish H3K9 Methylation, but Not Cytosine Methylation, on Geminivirus Chromatin.

PubMed

Jackel, Jamie N; Storer, Jessica M; Coursey, Tami; Bisaro, David M

2016-08-15

In plants, RNA-directed DNA methylation (RdDM) employs small RNAs to target enzymes that methylate cytosine residues. Cytosine methylation and dimethylation of histone 3 lysine 9 (H3K9me2) are often linked. Together they condition an epigenetic defense that results in chromatin compaction and transcriptional silencing of transposons and viral chromatin. Canonical RdDM (Pol IV-RdDM), involving RNA polymerases IV and V (Pol IV and Pol V), was believed to be necessary to establish cytosine methylation, which in turn could recruit H3K9 methyltransferases. However, recent studies have revealed that a pathway involving Pol II and RNA-dependent RNA polymerase 6 (RDR6) (RDR6-RdDM) is likely responsible for establishing cytosine methylation at naive loci, while Pol IV-RdDM acts to reinforce and maintain it. We used the geminivirus Beet curly top virus (BCTV) as a model to examine the roles of Pol IV and Pol V in establishing repressive viral chromatin methylation. As geminivirus chromatin is formed de novo in infected cells, these viruses are unique models for processes involved in the establishment of epigenetic marks. We confirm that Pol IV and Pol V are not needed to establish viral DNA methylation but are essential for its amplification. Remarkably, however, both Pol IV and Pol V are required for deposition of H3K9me2 on viral chromatin. Our findings suggest that cytosine methylation alone is not sufficient to trigger de novo deposition of H3K9me2 and further that Pol IV-RdDM is responsible for recruiting H3K9 methyltransferases to viral chromatin. In plants, RNA-directed DNA methylation (RdDM) uses small RNAs to target cytosine methylation, which is often linked to H3K9me2. These epigenetic marks silence transposable elements and DNA virus genomes, but how they are established is not well understood. Canonical RdDM, involving Pol IV and Pol V, was thought to establish cytosine methylation that in turn could recruit H3K9 methyltransferases, but recent studies compel a reevaluation of this view. We used BCTV to investigate the roles of Pol IV and Pol V in chromatin methylation. We found that both are needed to amplify, but not to establish, DNA methylation. However, both are required for deposition of H3K9me2. Our findings suggest that cytosine methylation is not sufficient to recruit H3K9 methyltransferases to naive viral chromatin and further that Pol IV-RdDM is responsible. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Regulation and Modulation of Human DNA Polymerase δ Activity and Function

PubMed Central

Wang, Xiaoxiao; Zhang, Sufang; Zhang, Zhongtao; Lee, Ernest Y. C.

2017-01-01

This review focuses on the regulation and modulation of human DNA polymerase δ (Pol δ). The emphasis is on the mechanisms that regulate the activity and properties of Pol δ in DNA repair and replication. The areas covered are the degradation of the p12 subunit of Pol δ, which converts it from a heterotetramer (Pol δ4) to a heterotrimer (Pol δ3), in response to DNA damage and also during the cell cycle. The biochemical mechanisms that lead to degradation of p12 are reviewed, as well as the properties of Pol δ4 and Pol δ3 that provide insights into their functions in DNA replication and repair. The second focus of the review involves the functions of two Pol δ binding proteins, polymerase delta interaction protein 46 (PDIP46) and polymerase delta interaction protein 38 (PDIP38), both of which are multi-functional proteins. PDIP46 is a novel activator of Pol δ4, and the impact of this function is discussed in relation to its potential roles in DNA replication. Several new models for the roles of Pol δ3 and Pol δ4 in leading and lagging strand DNA synthesis that integrate a role for PDIP46 are presented. PDIP38 has multiple cellular localizations including the mitochondria, the spliceosomes and the nucleus. It has been implicated in a number of cellular functions, including the regulation of specialized DNA polymerases, mitosis, the DNA damage response, mouse double minute 2 homolog (Mdm2) alternative splicing and the regulation of the NADPH oxidase 4 (Nox4). PMID:28737709

Characterization of the hyperrecombination phenotype of the pol3-t mutation of Saccharomyces cerevisiae.

PubMed

Galli, Alvaro; Cervelli, Tiziana; Schiestl, Robert H

2003-05-01

The DNA polymerase delta (Pol3p/Cdc2p) allele pol3-t of Saccharomyces cerevisiae has previously been shown to increase the frequency of deletions between short repeats (several base pairs), between homologous DNA sequences separated by long inverted repeats, and between distant short repeats, increasing the frequency of genomic deletions. We found that the pol3-t mutation increased intrachromosomal recombination events between direct DNA repeats up to 36-fold and interchromosomal recombination 14-fold. The hyperrecombination phenotype of pol3-t was partially dependent on the Rad52p function but much more so on Rad1p. However, in the double-mutant rad1 Delta rad52 Delta, the pol3-t mutation still increased spontaneous intrachromosomal recombination frequencies, suggesting that a Rad1p Rad52p-independent single-strand annealing pathway is involved. UV and gamma-rays were less potent inducers of recombination in the pol3-t mutant, indicating that Pol3p is partly involved in DNA-damage-induced recombination. In contrast, while UV- and gamma-ray-induced intrachromosomal recombination was almost completely abolished in the rad52 or the rad1 rad52 mutant, there was still good induction in those mutants in the pol3-t background, indicating channeling of lesions into the above-mentioned Rad1p Rad52p-independent pathway. Finally, a heterozygous pol3-t/POL3 mutant also showed an increased frequency of deletions and MMS sensitivity at the restrictive temperature, indicating that even a heterozygous polymerase delta mutation might increase the frequency of genetic instability.

Def1 interacts with TFIIH and modulates RNA polymerase II transcription.

PubMed

Damodaren, Nivedita; Van Eeuwen, Trevor; Zamel, Joanna; Lin-Shiao, Enrique; Kalisman, Nir; Murakami, Kenji

2017-12-12

The DNA damage response is an essential process for the survival of living cells. In a subset of stress-responsive genes in humans, Elongin controls transcription in response to multiple stimuli, such as DNA damage, oxidative stress, and heat shock. Yeast Elongin (Ela1-Elc1), along with Def1, is known to facilitate ubiquitylation and degradation of RNA polymerase II (pol II) in response to multiple stimuli, yet transcription activity has not been examined. We have found that Def1 copurifies from yeast whole-cell extract with TFIIH, the largest general transcription factor required for transcription initiation and nucleotide excision repair. The addition of recombinant Def1 and Ela1-Elc1 enhanced transcription initiation in an in vitro reconstituted system including pol II, the general transcription factors, and TFIIS. Def1 also enhanced transcription restart from TFIIS-induced cleavage in a pol II transcribing complex. In the Δdef1 strain, heat shock genes were misregulated, indicating that Def1 is required for induction of some stress-responsive genes in yeast. Taken together, our results extend the understanding of the molecular mechanism of transcription regulation on cellular stress and reveal functional similarities to the mammalian system.

Craniota, Wirbel- oder Schädeltiere

NASA Astrophysics Data System (ADS)

Schultze, Hans-Peter

Zu den Craniota zählen alle Chordatiere, die eine dreiteilige Regionalisierung des Körpers in Kopf, Rumpf und Schwanz aufweisen. Der Kopf umfasst (1) das Neurocranium mit Gehirn und komplexen Sinnesorganen zur Wahrnehmung der Umgebung, (2) das Viscerocranium zur Nahrungsaufnahme und zur Ventilation der Kiemen bei den primär wasserlebenden Craniota und (3) das Dermatocranium (S. 38). Letzteres entsteht durch Verknöcherungen im Bindegewebe des Integuments, es dient dem Schutz des Kopfes und trägt im Mundbreich die Zähne. Zusammen bilden die drei Skelettstrukturen die funktionelle Einheit Schädel (Cranium). Außer der (somatischen) Rumpfmuskulatur und dem Axialskelett liegen im Rumpf Kreislauf-, Atmungs-, Verdauungs-, Exkretions- und Fortpflanzungsorgane. Der Schwanz, der Abschnitt hinter der Afteröffnung, die das Ende der Leibeshöhle markiert, dient mit Muskeln und Schwanzflosse der Fortbewegung.

Modeling Subsurface Storm and Tile Drain Systems in GSSHA with SUPERLINK

DTIC Science & Technology

2014-09-01

side is computed as . ( )e Kq d m m L   2 0 01 2 (7) de is defined as ( van der Molen and Wesseling (1991)) ERDC/CHL TR-14-11 15...Conservation Service. Van der Molen , W.H., and J. Wesseling. 1991. A solution in closed form and a series solution to replace the tables for thickness of...effective lateral hydraulic conductivity (cm hr-1) C = 1 in the present version. Hooghoudt ( van Schilfgaarde 1974) characterized flow to cylindrical

The dynamic assembly of distinct RNA polymerase I complexes modulates rDNA transcription.

PubMed

Torreira, Eva; Louro, Jaime Alegrio; Pazos, Irene; González-Polo, Noelia; Gil-Carton, David; Duran, Ana Garcia; Tosi, Sébastien; Gallego, Oriol; Calvo, Olga; Fernández-Tornero, Carlos

2017-03-06

Cell growth requires synthesis of ribosomal RNA by RNA polymerase I (Pol I). Binding of initiation factor Rrn3 activates Pol I, fostering recruitment to ribosomal DNA promoters. This fundamental process must be precisely regulated to satisfy cell needs at any time. We present in vivo evidence that, when growth is arrested by nutrient deprivation, cells induce rapid clearance of Pol I-Rrn3 complexes, followed by the assembly of inactive Pol I homodimers. This dual repressive mechanism reverts upon nutrient addition, thus restoring cell growth. Moreover, Pol I dimers also form after inhibition of either ribosome biogenesis or protein synthesis. Our mutational analysis, based on the electron cryomicroscopy structures of monomeric Pol I alone and in complex with Rrn3, underscores the central role of subunits A43 and A14 in the regulation of differential Pol I complexes assembly and subsequent promoter association.

Exonuclease of human DNA polymerase gamma disengages its strand displacement function.

PubMed

He, Quan; Shumate, Christie K; White, Mark A; Molineux, Ian J; Yin, Y Whitney

2013-11-01

Pol γ, the only DNA polymerase found in human mitochondria, functions in both mtDNA repair and replication. During mtDNA base-excision repair, gaps are created after damaged base excision. Here we show that Pol γ efficiently gap-fills except when the gap is only a single nucleotide. Although wild-type Pol γ has very limited ability for strand displacement DNA synthesis, exo(-) (3'-5' exonuclease-deficient) Pol γ has significantly high activity and rapidly unwinds downstream DNA, synthesizing DNA at a rate comparable to that of the wild-type enzyme on a primer-template. The catalytic subunit Pol γA alone, even when exo(-), is unable to synthesize by strand displacement, making this the only known reaction of Pol γ holoenzyme that has an absolute requirement for the accessory subunit Pol γB. © 2013. Published by Elsevier B.V.

Genomic binding profiles of functionally distinct RNA polymerase III transcription complexes in human cells.

PubMed

Moqtaderi, Zarmik; Wang, Jie; Raha, Debasish; White, Robert J; Snyder, Michael; Weng, Zhiping; Struhl, Kevin

2010-05-01

Genome-wide occupancy profiles of five components of the RNA polymerase III (Pol III) machinery in human cells identified the expected tRNA and noncoding RNA targets and revealed many additional Pol III-associated loci, mostly near short interspersed elements (SINEs). Several genes are targets of an alternative transcription factor IIIB (TFIIIB) containing Brf2 instead of Brf1 and have extremely low levels of TFIIIC. Strikingly, expressed Pol III genes, unlike nonexpressed Pol III genes, are situated in regions with a pattern of histone modifications associated with functional Pol II promoters. TFIIIC alone associates with numerous ETC loci, via the B box or a novel motif. ETCs are often near CTCF binding sites, suggesting a potential role in chromosome organization. Our results suggest that human Pol III complexes associate preferentially with regions near functional Pol II promoters and that TFIIIC-mediated recruitment of TFIIIB is regulated in a locus-specific manner.

Genomic Binding Profiles of Functionally Distinct RNA Polymerase III Transcription Complexes in Human Cells

PubMed Central

Moqtaderi, Zarmik; Wang, Jie; Raha, Debasish; White, Robert J.; Snyder, Michael; Weng, Zhiping; Struhl, Kevin

2012-01-01

Genome-wide occupancy profiles of five components of the RNA Polymerase III (Pol III) machinery in human cells identified the expected tRNA and non-coding RNA targets and revealed many additional Pol III-associated loci, mostly near SINEs. Several genes are targets of an alternative TFIIIB containing Brf2 instead of Brf1 and have extremely low levels of TFIIIC. Strikingly, expressed Pol III genes, unlike non-expressed Pol III genes, are situated in regions with a pattern of histone modifications associated with functional Pol II promoters. TFIIIC alone associates with numerous ETC loci, via the B box or a novel motif. ETCs are often near CTCF binding sites, suggesting a potential role in chromosome organization. Our results suggest that human Pol III complexes associate preferentially with regions near functional Pol II promoters and that TFIIIC-mediated recruitment of TFIIIB is regulated in a locus-specific manner. PMID:20418883

Role for the MED21-MED7 Hinge in Assembly of the Mediator-RNA Polymerase II Holoenzyme*

PubMed Central

Sato, Shigeo; Tomomori-Sato, Chieri; Tsai, Kuang-Lei; Yu, Xiaodi; Sardiu, Mihaela; Saraf, Anita; Washburn, Michael P.; Florens, Laurence; Asturias, Francisco J.; Conaway, Ronald C.

2016-01-01

Mediator plays an integral role in activation of RNA polymerase II (Pol II) transcription. A key step in activation is binding of Mediator to Pol II to form the Mediator-Pol II holoenzyme. Here, we exploit a combination of biochemistry and macromolecular EM to investigate holoenzyme assembly. We identify a subset of human Mediator head module subunits that bind Pol II independent of other subunits and thus probably contribute to a major Pol II binding site. In addition, we show that binding of human Mediator to Pol II depends on the integrity of a conserved “hinge” in the middle module MED21-MED7 heterodimer. Point mutations in the hinge region leave core Mediator intact but lead to increased disorder of the middle module and markedly reduced affinity for Pol II. These findings highlight the importance of Mediator conformation for holoenzyme assembly. PMID:27821593

Eukaryotic DNA polymerase ζ

PubMed Central

Makarova, Alena V.; Burgers, Peter M.

2015-01-01

This review focuses on eukaryotic DNA polymerase ζ (Pol ζ), the enzyme responsible for the bulk of mutagenesis in eukaryotic cells in response to DNA damage. Pol ζ is also responsible for a large portion of mutagenesis during normal cell growth, in response to spontaneous damage or to certain DNA structures and other blocks that stall DNA replication forks. Novel insights in mutagenesis have been derived from recent advances in the elucidation of the subunit structure of Pol ζ. The lagging strand DNA polymerase δ shares the small Pol31 and Pol32 subunits with the Rev3-Rev7 core assembly giving a four subunit Pol ζ complex that is the active form in mutagenesis. Furthermore, Pol ζ forms essential interactions with the mutasome assembly factor Rev1 and with proliferating cell nuclear antigen (PCNA). These interactions are modulated by posttranslational modifications such as ubiquitination and phosphorylation that enhance translesion synthesis (TLS) and mutagenesis. PMID:25737057

Meilensteine in der Erforschung der kompakten Objekte

NASA Astrophysics Data System (ADS)

Camenzind, Max

Kompakte Objekte besitzen zum einen eine sehr hohe Dichte, und zum anderen sind sie durch die Tatsache charakterisiert, dass keine nuklearen Reaktionen mehr in ihrem Inneren stattfinden können. Aus diesem Grund können sie im Unterschied zu gewöhnlichen Sternen der Gravitation nicht mehr mit dem Druck des thermischen Gases widerstehen. In den Weißen Zwergen bzw. Neutronensternen wird der Gravitation der Quantendruck eines Elektronengases bzw. einer Neutronenflüssigkeit entgegengesetzt. Ein solches Gas besteht aus Elektronen bzw. Neutronen, die auf ihr niedrigstes Energieniveau zusammengepresst wurden. Durch die daraus resultierende hohe Bewegungsenergie der Fermionen wird der sogenannte Quantendruck erzeugt.

Extrusion & Compoundierung

NASA Astrophysics Data System (ADS)

Collin, Heinz; Schulze, Verena

Unter Extrusion wird das kontinuierliche Fördern von formbaren Massen verstanden. Dies können Kunststoffe, Teigwaren in der Lebensmittelindustrie oder auch keramische Massen sein. In der chemischen Industrie werden ebenfalls hochviskose (schwerfließende) Stoffe oder Pasten dosiert, gefördert und extrudiert. Früher waren vorzugsweise Kolbenstrangpressen im Einsatz, bis sich ab 1950 in steigendem Maße die Schneckenmaschinen durchgesetzt haben. Der weltweite Siegeszug der Kunststoffe ist zu einem erheblichen Teil auf die stetige technologische Weiterentwicklung im Bereich der Extrusionstechnik zurückzuführen. Der Markt der weltweit produzierten Maschinen für die Kunststoffverarbeitung erreichte im Jahr 2006 einen Wert von 20 Milliarden Euro und somit zählt dieser Bereich mittlerweile zu einem der großen Industriezweige [1].

Implantate in der Augenheilkunde

NASA Astrophysics Data System (ADS)

Dresp, Joachim H.

Im Bereich der Augenheilkunde findet sich die weltweit am häufigsten ausgeführte chirurgische Massnahme, die operative Behandlung des Grauen Stars: die Katarakt. Bei der Katarakt handelt es sich um eine Eintrübung der natürlichen Augenlinse, die sich je nach Stadium der Erkrankung leicht opak, über milchig bis zu bräunlich präsentiert. Mit dieser Zunahme der Undurchlässigkeit für das sichtbare Licht geht eine Abnahme des Sehvermögens einher, die bis zur totalen Erblindung führen kann. Bedingt durch die sehr eingeschränkten chirurgischen Möglichkeiten in den Ländern der Dritten Welt ist die Katarakt die Erblindungsursache Nummer 1 in der Welt. Ganz im Gegensatz hierzu ist in den industrialisierten Ländern Europas, Amerikas und Asiens die Katarakt-OP die sicherste chirurgische Intervention. In der Augenheilkunde werden Implantate aller drei Aggregatszustände verwendet.

Lesion bypass by S. cerevisiae Pol ζ alone

PubMed Central

Stone, Jana E.; Kumar, Dinesh; Binz, Sara K.; Inase, Aki; Iwai, Shigenori; Chabes, Andrei; Burgers, Peter M.; Kunkel, Thomas A.

2011-01-01

DNA polymerase zeta (Pol ζ) participates in translesion synthesis (TLS) of DNA adducts that stall replication fork progression. Previous studies have led to the suggestion that the primary role of Pol ζ in TLS is to extend primers created when another DNA polymerase inserts nucleotides opposite lesions. Here we test the non-exclusive possibility that Pol ζ can sometimes perform TLS in the absence of any other polymerase. To do so, we quantified the efficiency with which S. cerevisiae Pol ζ bypasses abasic sites, cis-syn cyclobutane pyrimidine dimers and (6-4) photoproducts. In reactions containing dNTP concentrations that mimic those induced by DNA damage, a Pol ζ derivative with phenylalanine substituted for leucine 979 at the polymerase active site bypasses all three lesions at efficiencies between 27–73%. Wild-type Pol ζ also bypasses these lesions, with efficiencies that are lower and depend on the sequence context in which the lesion resides. The results are consistent with the hypothesis that, in addition to extending aberrant termini created by other DNA polymerases, Pol ζ has the potential to be the sole DNA polymerase involved in TLS. PMID:21622032

Involvement of the Reparative DNA Polymerase Pol X of African Swine Fever Virus in the Maintenance of Viral Genome Stability In Vivo

PubMed Central

Redrejo-Rodríguez, Modesto; Rodríguez, Javier M.; Suárez, Cristina; Salas, José

2013-01-01

The function of the African swine fever virus (ASFV) reparative DNA polymerase, Pol X, was investigated in the context of virus infection. Pol X is a late structural protein that localizes at cytoplasmic viral factories during DNA replication. Using an ASFV deletion mutant lacking the Pol X gene, we have shown that Pol X is not required for virus growth in Vero cells or swine macrophages under one-step growth conditions. However, at a low multiplicity of infection, when multiple rounds of replication occur, the growth of the mutant virus is impaired in swine macrophages but not in Vero cells, suggesting that Pol X is needed to repair the accumulated DNA damage. The replication of the mutant virus in Vero cells presents sensitivity to oxidative damage, and mutational analysis of viral DNA shows that deletion of Pol X results in an increase in the mutation frequency in macrophages. Therefore, our data reveal a biological role for ASFV Pol X in the context of the infected cell in the preservation of viral genetic information. PMID:23824796

Structure of the initiation-competent RNA polymerase I and its implication for transcription

NASA Astrophysics Data System (ADS)

Pilsl, Michael; Crucifix, Corinne; Papai, Gabor; Krupp, Ferdinand; Steinbauer, Robert; Griesenbeck, Joachim; Milkereit, Philipp; Tschochner, Herbert; Schultz, Patrick

2016-07-01

Eukaryotic RNA polymerase I (Pol I) is specialized in rRNA gene transcription synthesizing up to 60% of cellular RNA. High level rRNA production relies on efficient binding of initiation factors to the rRNA gene promoter and recruitment of Pol I complexes containing initiation factor Rrn3. Here, we determine the cryo-EM structure of the Pol I-Rrn3 complex at 7.5 Å resolution, and compare it with Rrn3-free monomeric and dimeric Pol I. We observe that Rrn3 contacts the Pol I A43/A14 stalk and subunits A190 and AC40, that association re-organizes the Rrn3 interaction interface, thereby preventing Pol I dimerization; and Rrn3-bound and monomeric Pol I differ from the dimeric enzyme in cleft opening, and localization of the A12.2 C-terminus in the active centre. Our findings thus support a dual role for Rrn3 in transcription initiation to stabilize a monomeric initiation competent Pol I and to drive pre-initiation complex formation.

Characterization of a Y-Family DNA Polymerase eta from the Eukaryotic Thermophile Alvinella pompejana

DOE PAGES

Kashiwagi, Sayo; Kuraoka, Isao; Fujiwara, Yoshie; ...

2010-01-01

Humore » man DNA polymerase η (HsPol η ) plays an important role in translesion synthesis (TLS), which allows for replication past DNA damage such as UV-induced cis-syn cyclobutane pyrimidine dimers (CPDs). Here, we characterized ApPol η from the thermophilic worm Alvinella pompejana , which inhabits deep-sea hydrothermal vent chimneys. ApPol η shares sequence homology with HsPol η and contains domains for binding ubiquitin and proliferating cell nuclear antigen. Sun-induced UV does not penetrate Alvinella's environment; however, this novel DNA polymerase catalyzed efficient and accurate TLS past CPD, as well as 7,8-dihydro-8-oxoguanine and isomers of thymine glycol induced by reactive oxygen species. In addition, we found that ApPol η is more thermostable than HsPol η , as expected from its habitat temperature. Moreover, the activity of this enzyme was retained in the presence of a higher concentration of organic solvents. Therefore, ApPol η provides a robust, human-like Pol η that is more active after exposure to high temperatures and organic solvents.« less

Characterization of a Y-Family DNA Polymerase eta from the Eukaryotic Thermophile Alvinella pompejana

PubMed Central

Kashiwagi, Sayo; Kuraoka, Isao; Fujiwara, Yoshie; Hitomi, Kenichi; Cheng, Quen J.; Fuss, Jill O.; Shin, David S.; Masutani, Chikahide; Tainer, John A.; Hanaoka, Fumio; Iwai, Shigenori

2010-01-01

Human DNA polymerase η (HsPolη) plays an important role in translesion synthesis (TLS), which allows for replication past DNA damage such as UV-induced cis-syn cyclobutane pyrimidine dimers (CPDs). Here, we characterized ApPolη from the thermophilic worm Alvinella pompejana, which inhabits deep-sea hydrothermal vent chimneys. ApPolη shares sequence homology with HsPolη and contains domains for binding ubiquitin and proliferating cell nuclear antigen. Sun-induced UV does not penetrate Alvinella's environment; however, this novel DNA polymerase catalyzed efficient and accurate TLS past CPD, as well as 7,8-dihydro-8-oxoguanine and isomers of thymine glycol induced by reactive oxygen species. In addition, we found that ApPolη is more thermostable than HsPolη, as expected from its habitat temperature. Moreover, the activity of this enzyme was retained in the presence of a higher concentration of organic solvents. Therefore, ApPolη provides a robust, human-like Polη that is more active after exposure to high temperatures and organic solvents. PMID:20936172

Nuclear DNA polymerase beta from Leishmania infantum. Cloning, molecular analysis and developmental regulation

PubMed Central

Taladriz, Soraya; Hanke, Tobias; Ramiro, María J.; García-Díaz, Miguel; Lacoba, Mario García de; Blanco, Luis; Larraga, Vicente

2001-01-01

We have identified a novel polymerase beta (Pol β)-like enzyme from Leishmania infantum, a parasite protozoon causing disease in humans. This protein, named Li Pol β, shows a nuclear localization that contrasts with the mitochondrial localization of Pol β from Crithidia fasciculata, a closely related parasite, the only polymerase β described so far in Trypanosomatidae. Li Pol β, that belongs to the DNA polymerase X family, displays an evolutionarily conserved Pol β-type DNA polymerase core, in which most of the key residues involved in DNA binding, nucleotide binding, dRPase and polymerization catalysis are conserved. In agreement with this, Li Pol β, overproduced in Escherichia coli, displayed intrinsic DNA polymerase activity. Cell synchronization experiments showed a correlation between both Li Pol β mRNA and protein levels along the parasite cell cycle. Analysis of these parameters at the different growth phases of the parasite, from the proliferative (non-infective) logarithmic phase to the non-dividing (highly infectious) stationary phase, showed high levels of Li Pol β at the infective phase of the parasite. The data suggest a role of Li Pol β in base excision repair in L.infantum, a parasite usually affected by oxygen stress environments into the macrophage host cells. PMID:11557814

Foamy virus reverse transcriptase is expressed independently from the Gag protein.

PubMed Central

Enssle, J; Jordan, I; Mauer, B; Rethwilm, A

1996-01-01

In the foamy virus (FV) subgroup of retroviruses the pol genes are located in the +1 reading frame relative to the gag genes and possess potential ATG initiation codons in their 5' regions. This genome organization suggests either a + 1 ribosomal frameshift to generate a Gag-Pol fusion protein, similar to all other retroviruses studied so far, or new initiation of Pol translation, as used by pararetroviruses, to express the Pol protein. By using a genetic approach we have ruled out the former possibility and provide evidence for the latter. Two down-mutations (M53 and M54) of the pol ATG codon were found to abolish replication and Pol protein expression of the human FV isolate. The introduction of a new ATG in mutation M55, 3' to the down-mutated ATG of mutation M53, restored replication competence, indicating that the pol ATG functions as a translational initiation codon. Two nonsense mutants (M56 and M57), which functionally separated gag and pol with respect to potential frame-shifting sites, were also replication-competent, providing further genetic evidence that FVs express the Pol protein independently from Gag. Our results show that during a particular step of the replication cycle, FVs differ fundamentally from all other retroviruses. Images Fig. 3 PMID:8633029

Human cytomegalovirus and Herpes Simplex type I virus can engage RNA polymerase I for transcription of immediate early genes

PubMed Central

Kostopoulou, Ourania N.; Wilhelmi, Vanessa; Raiss, Sina; Ananthaseshan, Sharan; Lindström, Mikael S.; Bartek, Jiri; Söderberg-Naucler, Cecilia

2017-01-01

Human cytomegalovirus (HCMV) utilizes RNA polymerase II to transcribe viral genes and produce viral mRNAs. It can specifically target the nucleolus to facilitate viral transcription and translation. As RNA polymerase I (Pol I)-mediated transcription is active in the nucleolus, we investigated the role of Pol I, along with relative contributions of the human Pol II and Pol III, to early phases of viral transcription in HCMV infected cells, compared with Herpes Simplex Virus-1 (HSV-1) and Murine cytomegalovirus (MCMV). Inhibition of Pol I with siRNA or the Pol I inhibitors CX-5461 or Actinomycin D (5nM) resulted in significantly decreased IE and pp65 mRNA and protein levels in human fibroblasts at early times post infection. This initially delayed replication was compensated for later during the replication process, at which stage it didn’t significantly affect virus production. Pol I inhibition also reduced HSV-1 ICP0 and gB transcripts, suggesting that some herpesviruses engage Pol I for their early transcription. In contrast, inhibition of Pol I failed to affect MCMV transcription. Collectively, our results contribute to better understanding of the functional interplay between RNA Pol I-mediated nucleolar events and the Herpes viruses, particularly HCMV whose pathogenic impact ranges from congenital malformations and potentially deadly infections among immunosuppressed patients, up to HCMV’s emerging oncomodulatory role in human tumors. PMID:29228551

DNA stabilization at the Bacillus subtilis PolX core—a binding model to coordinate polymerase, AP-endonuclease and 3′-5′ exonuclease activities

PubMed Central

Baños, Benito; Villar, Laurentino; Salas, Margarita; de Vega, Miguel

2012-01-01

Family X DNA polymerases (PolXs) are involved in DNA repair. Their binding to gapped DNAs relies on two conserved helix-hairpin-helix motifs, one located at the 8-kDa domain and the other at the fingers subdomain. Bacterial/archaeal PolXs have a specifically conserved third helix-hairpin-helix motif (GFGxK) at the fingers subdomain whose putative role in DNA binding had not been established. Here, mutagenesis at the corresponding residues of Bacillus subtilis PolX (PolXBs), Gly130, Gly132 and Lys134 produced enzymes with altered DNA binding properties affecting the three enzymatic activities of the protein: polymerization, located at the PolX core, 3′-5′ exonucleolysis and apurinic/apyrimidinic (AP)-endonucleolysis, placed at the so-called polymerase and histidinol phosphatase domain. Furthermore, we have changed Lys192 of PolXBs, a residue moderately conserved in the palm subdomain of bacterial PolXs and immediately preceding two catalytic aspartates of the polymerization reaction. The results point to a function of residue Lys192 in guaranteeing the right orientation of the DNA substrates at the polymerization and histidinol phosphatase active sites. The results presented here and the recently solved structures of other bacterial PolX ternary complexes lead us to propose a structural model to account for the appropriate coordination of the different catalytic activities of bacterial PolXs. PMID:22844091

DNA polymerase θ (POLQ) can extend from mismatches and from bases opposite a (6–4) photoproduct

PubMed Central

Seki, Mineaki; Wood, Richard D.

2007-01-01

DNA polymerase θ (pol θ) is a nuclear A-family DNA polymerase encoded by the POLQ gene in vertebrate cells. The biochemical properties of pol θ and of Polq-defective mice have suggested that pol θ participates in DNA damage tolerance. For example, pol θ was previously found to be proficient not only in incorporation of a nucleotide opposite a thymine glycol or an abasic site, but also extends a polynucleotide chain efficiently from the base opposite the lesion. We carried out experiments to determine whether this ability to extend from non-standard termini is a more general property of the enzyme. Pol θ extended relatively efficiently from matched termini as well as termini with A:G, A:T, and A:C mismatches, with less descrimination than a well-studied A family DNA polymerase, exonuclease-free pol I from E. coli. Although pol θ was unable to, by itself, bypass a cyclobutane pyrimidine dimer or a (6–4) photoproduct, it could perform some extension from primers with bases placed across from these lesions. When pol θ was combined with DNA polymerase ι , an enzyme that can insert a base opposite a UV-induced (6–4) photoproduct, complete bypass of a (6–4) photoproduct was possible. These data show that in addition to its ability to insert nucleotides opposite some DNA lesions, pol θ is proficient at extension of unpaired termini. These results show the potential of pol θ to act as an extender after incorporation of nucleotides by other DNA polymerases, and aid in understanding the role of pol θ in somatic mutagenesis and genome instability. PMID:17920341

DNA polymerase theta (POLQ) can extend from mismatches and from bases opposite a (6-4) photoproduct.

PubMed

Seki, Mineaki; Wood, Richard D

2008-01-01

DNA polymerase theta (pol theta) is a nuclear A-family DNA polymerase encoded by the POLQ gene in vertebrate cells. The biochemical properties of pol theta and of Polq-defective mice have suggested that pol theta participates in DNA damage tolerance. For example, pol theta was previously found to be proficient not only in incorporation of a nucleotide opposite a thymine glycol or an abasic site, but also extends a polynucleotide chain efficiently from the base opposite the lesion. We carried out experiments to determine whether this ability to extend from non-standard termini is a more general property of the enzyme. Pol theta extended relatively efficiently from matched termini as well as termini with A:G, A:T and A:C mismatches, with less descrimination than a well-studied A-family DNA polymerase, exonuclease-free pol I from E. coli. Although pol theta was unable to, by itself, bypass a cyclobutane pyrimidine dimer or a (6-4) photoproduct, it could perform some extension from primers with bases placed across from these lesions. When pol theta was combined with DNA polymerase iota, an enzyme that can insert a base opposite a UV-induced (6-4) photoproduct, complete bypass of a (6-4) photoproduct was possible. These data show that in addition to its ability to insert nucleotides opposite some DNA lesions, pol theta is proficient at extension of unpaired termini. These results show the potential of pol theta to act as an extender after incorporation of nucleotides by other DNA polymerases, and aid in understanding the role of pol theta in somatic mutagenesis and genome instability.

Alteration of BRCA1 expression affects alcohol-induced transcription of RNA Pol III-dependent genes.

PubMed

Zhong, Qian; Shi, Ganggang; Zhang, Yanmei; Lu, Lei; Levy, Daniel; Zhong, Shuping

2015-02-01

Emerging evidence has indicated that alcohol consumption is an established risk factor for breast cancer. Deregulation of RNA polymerase III (Pol III) transcription enhances cellular Pol III gene production, leading to an increase in translational capacity to promote cell transformation and tumor formation. We have reported that alcohol intake increases Pol III gene transcription to promote cell transformation and tumor formation in vitro and in vivo. Studies revealed that tumor suppressors, pRb, p53, PTEN and Maf1 repress the transcription of Pol III genes. BRCA1 is a tumor suppressor and its mutation is tightly related to breast cancer development. However, it is not clear whether BRCA1 expression affects alcohol-induced transcription of Pol III genes. At the present studies, we report that restoring BRCA1 in HCC 1937 cells, which is a BRCA1 deficient cell line, represses Pol III gene transcription. Expressing mutant or truncated BRCA1 in these cells does not affect the ability of repression on Pol III genes. Our analysis has demonstrated that alcohol induces Pol III gene transcription. More importantly, overexpression of BRCA1 in estrogen receptor positive (ER+) breast cancer cells (MCF-7) decreases the induction of tRNA(Leu) and 5S rRNA genes by alcohol, whereas reduction of BRCA1 by its siRNA slightly increases the transcription of the class of genes. This suggests that BRCA1 is associated with alcohol-induced deregulation of Pol III genes. These studies for the first time demonstrate the role of BRCA1 in induction of Pol III genes by alcohol and uncover a novel mechanism of alcohol-associated breast cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

Wirkungen biogener Amine auf die Erregungs-Sekretions-Kopplung in der Speicheldrüse von Periplaneta americana (L.)

NASA Astrophysics Data System (ADS)

Rietdorf, Katja

2003-07-01

In der vorliegenden Arbeit habe ich wichtige Teilmechanismen der Erregungs-Sekretionskopplung in der Speicheldrüse der Schabe Periplaneta americana (L.) untersucht. Die Speicheldrüse ist von dopaminergen und serotonergen Fasern innerviert (Baumann et al., 2002). Beide Transmitter stimulieren eine unterschiedliche Reaktion der Drüse: Dopamin (DA) stimuliert die P-Zellen der Acini und die Ausführgangzellen, während Serotonin (5-HT) die P- und C-Zellen der Acini stimuliert, nicht jedoch die Ausführgangzellen. Der Endspeichel ist nach einer DA-Stimulierung proteinfrei. Dagegen enthält er nach einer 5-HT-Stimulierung Proteine, die von den C-Zellen sezerniert werden (Just & Walz, 1996). Im ersten Teil meiner Arbeit habe ich mittels Kapillarelektrophoretischer Analyse (CE-Analyse) die Elektrolytkonzentrationen im Endspeichel untersucht sowie die Raten der Flüssigkeitssekretion gemessen. Damit wollte ich klären, welche Transporter an der Sekretion des Primärspeichels und an dessen Modifikation beteiligt sind. Ausserdem wollte ich die Rolle der transportaktiven Epithelzellen der Ausführgänge für die Modifikation des Primärspeichels untersuchen. Dafür habe ich einen Vergleich der Elektrolytkonzentrationen im DA- und 5-HT-stimulierten Endspeichel durchgeführt. Der Elektrolytgehalt des DA- und 5-HT-stimulierten Endspeichels unterscheidet sich nicht signifikant voneinander. Er ist nach beiden Stimulierungen hypoosmotisch zum verwendeten Ringer. Die Ausführgangzellen werden durch DA stimuliert und modifizieren den Primärspeichel durch eine netto-Ionenreabsorption. Meine Versuche zeigen jedoch, dass auch die während einer 5-HT-Stimulierung der Drüse unstimulierten Ausführgangzellen den Primärspeichel modifizieren. In einer nachfolgenden Versuchsreihe habe ich den Einfluss von Ouabain, einem Hemmstoff der Na+-K+-ATPase, und Bumetanid, einem Hemmstoff des NKCC, auf die Raten der Flüssigkeitssekretion sowie den Elektrolytgehalt des Endspeichels untersucht. Ich habe gefunden, dass die Aktivität der Na+-K+-ATPase wichtig für die Modifikation des DA-stimulierten Primärspeichels ist. Im Gegensatz dazu ist sie für die Modifikation des 5-HT-stimulierten Primärspeichels nicht von Bedeutung. Bezüglich der Flüssigkeitssekretion habe ich keinen Einfluss der Na+-K+-ATPase-Aktivität auf die DA-stimulierten Sekretionsraten gefunden, dagegen ist die 5-HT-stimulierte Sekretionsrate in Anwesenheit von Ouabain gesteigert. Die Aktivität des NKCC ist für beide sekretorische Prozesse, die Ionen- und die Flüssigkeitssekretion, wichtig. Eine Hemmung des NKCC bewirkt eine signifikante Verringerung der Raten der Flüssigkeitssekretion nach DA- und 5-HT-Stimulierung sowie in beiden Fällen einen signifikanten Abfall der Ionenkonzentrationen im Endspeichel. Im zweiten Teil meiner Arbeit habe ich versucht, Änderungen der intrazellulären Ionenkonzentrationen in den Acinuszellen während einer DA- oder 5-HT-Stimulierung zu messen. Diese Experimente sollten mit der Methode des "ratiometric imaging" durchgeführt werden. Messungen mit dem Ca2+-sensitiven Fluoreszenzfarbstoff Fura-2 zeigten keinen globalen Anstieg in der intrazellulären Ca2+-Konzentration der P-Zellen. Aufgrund von Problemen mit einer schlechten Beladung der Zellen, einer starken und sich während der Stimulierung ändernden Autofluoreszenz der Zellen sowie Änderungen im Zellvolumen wurden keine Messungen mit Na+- und K+-sensitiven Fluoreszenzfarbstoffen durchgeführt. Im dritten Teil dieser Arbeit habe ich die intrazellulären Signalwege untersucht, die zwischen einer 5-HT-Stimulierung der Drüse und der Proteinsekretion vermitteln. Dazu wurde der Proteingehalt im Endspeichel biochemisch mittels eines modifizierten Bradford Assay gemessen. Eine erstellte Dosis-Wirkungskurve zeigt, dass die Rate der Proteinsekretion von der zur Stimulierung verwendeten 5-HT-Konzentration abhängt. In einer Serie von Experimenten habe ich die intrazellulären Konzentrationen von Ca2+, cAMP und / oder cGMP erhöht und anschließend den Proteingehalt im Endspeichel gemessen. Ein Anstieg der intrazellulären Ca2+-Konzentration aktiviert nur eine geringe Rate der Proteinsekretion. Dagegen kann die Steigerung der intrazellulären cAMP-Konzentration eine stärkere Proteinsekretion aktivieren, die sich nicht signifikant von der nach 5-HT-Stimulierung unterscheidet. Die cAMP-stimulierte Proteinsekretion kann durch gleichzeitige Erhöhung der intrazellulären Ca2+-Konzentration weiter gesteigert werden. Dagegen aktivierte eine Erhöhung der intrazellulären cGMP-Konzentration die Proteinsekretion nicht. Aufgrund dieser Ergebnisse postuliere ich die Existenz eines die Adenylatcyclase aktivierenden 5-HT-Rezeptors in der Basolateralmembran der C-Zellen. The aim of this PhD-work was to investigate major mechanisms of excitation-secretion coupling in the salivary gland of the cockroach Periplaneta americana (L.). This salivary gland is innervated by dopaminergic and serotonergic fibres (Baumann et al., 2002). The two transmitters stimulate different processes in the gland: Dopamine (DA) stimulates the p-cells of the acini and the salivary duct cells, whereas 5-HT (serotonin) activates the p- and the c-cells of the acini, but not the salivary duct cells. Final saliva is completely protein-free after dopamine stimulation. It contains proteins, which are secreted by the c-cells of the acini, after a 5-HT-stimulation (Just & Walz, 1996). In the first part of my work I measured the electrolytic composition of the final saliva by capillary electrophoretic analysis and measured the rates of fluid secretion, in order to answer the following questions: 1.) Which transporters affect the production of primary saliva and its modification? 2.) What is the function of the transport-active salivary duct cells for the modification of the primary saliva? Electrolytic composition of the DA- and 5-HT-stimulated final saliva is not significantly different from each other, and is hypoosmotic to the Ringer used. Salivary duct cells are stimulated by DA and modify the primary saliva by a netto ion-reabsorption. My experiments also show that the duct cells, which are unstimulated during a 5-HT-stimulation of the gland, modify the primary saliva. In the next series of experiments I investigated the effects of ouabain, an inhibitor of the Na+-K+-ATPase, and bumetanide, an inhibitor of the NKCC on the rates of fluid secretion and the electrolytic composition of the final saliva. I found, that the activity of the Na+-K+-ATPase is important for the modification of DA-stimulated primary saliva during its flow through the stimulated duct system. In contrast, it is not important for modification of the 5-HT-stimulated primary saliva. Inhibition of the Na+-K+-ATPase does not affect rates of DA-stimulated fluid secretion, but it increases the rates of 5-HT-stimulated fluid secretion. Activity of the NKCC is important for both secretory processes: the ion and the fluid secretion. Inhibition of the NKCC results in a significant drop in the rates of fluid secretion after DA- and 5-HT-stimulation, as well as a drop in electrolytic concentrations in the saliva. In the second part of my work, I tried to measure changes in the intracellular ionic concentrations (Ca2+, Na+, and K+) within the acinar cells during a DA- or 5-HT-stimulation. The experiments should be performed by ratiometric imaging. Measurements with the Ca2+-sensitive dye Fura-2 did not show any global increase in the intracellular Ca2+-concentration in the p-cells of the acini. Problems concerning a bad loading of the cells, a strong autofluorescence which changed during the time course of the stimulation, as well as changes in the cell volume were the reason, that no measurements using Na+- or K+-sensitive dyes were performed. In the third part of my work I investigated the intracellular signalling pathways, which activate protein secretion after 5-HT-stimulation of the gland. A modified Bradford Assay was used for measuring the protein content in the final saliva. In a dose-response curve I showed that rates of protein secretion are dependent on the 5-HT-concentrations used to stimulate the glands. In another set of experiments I increased the intracellular concentrations of Ca2+, cAMP and / or cGMP, and measured the protein content in the final saliva. An increase in the intracellular Ca2+-concentration activates only a low rate of protein secretion. After an increase in the intracellular cAMP-concentration a much higher rate of protein secretion can be activated, which is not significantly different from the 5-HT stimulated rate of protein secretion. The cAMP-stimulated protein secretion can be further increased by a simultaneous rise in the intracellular Ca2+-concentration. In contrast, cGMP does not activate protein secretion. Therefore I propose the expression of an adenylyl cyclase activating 5-HT-receptor in the basolateral membrane of the protein secreting c-cells.

Generalization of the van der Pauw Method: Analyzing Longitudinal Magnetoresistance Asymmetry to Quantify Doping Gradients

NASA Astrophysics Data System (ADS)

Grayson, M.; Zhou, Wang; Yoo, Heun-Mo; Prabhu-Gaunkar, S.; Tiemann, L.; Reichl, C.; Wegscheider, W.

A longitudinal magnetoresistance asymmetry (LMA) between a positive and negative magnetic field is known to occur in both the extreme quantum limit and the classical Drude limit in samples with a nonuniform doping density. By analyzing the current stream function in van der Pauw measurement geometry, it is shown that the electron density gradient can be quantitatively deduced from this LMA in the Drude regime. Results agree with gradients interpolated from local densities calibrated across an entire wafer, establishing a generalization of the van der Pauw method to quantify density gradients. Results will be shown of various semoconductor systems where this method is applied, from bulk doped semiconductors, to exfoliated 2D materials. McCormick Catalyst Award from Northwestern University, EECS Bridge Funding, and AFOSR FA9550-15-1-0247.

UVB Induces a Genome-Wide Acting Negative Regulatory Mechanism That Operates at the Level of Transcription Initiation in Human Cells

PubMed Central

Gyenis, Ákos; Umlauf, David; Újfaludi, Zsuzsanna; Boros, Imre; Ye, Tao; Tora, Làszlò

2014-01-01

Faithful transcription of DNA is constantly threatened by different endogenous and environmental genotoxic effects. Transcription coupled repair (TCR) has been described to stop transcription and quickly remove DNA lesions from the transcribed strand of active genes, permitting rapid resumption of blocked transcription. This repair mechanism has been well characterized in the past using individual target genes. Moreover, numerous efforts investigated the fate of blocked RNA polymerase II (Pol II) during DNA repair mechanisms and suggested that stopped Pol II complexes can either backtrack, be removed and degraded or bypass the lesions to allow TCR. We investigated the effect of a non-lethal dose of UVB on global DNA-bound Pol II distribution in human cells. We found that the used UVB dose did not induce Pol II degradation however surprisingly at about 93% of the promoters of all expressed genes Pol II occupancy was seriously reduced 2–4 hours following UVB irradiation. The presence of Pol II at these cleared promoters was restored 5–6 hours after irradiation, indicating that the negative regulation is very dynamic. We also identified a small set of genes (including several p53 regulated genes), where the UVB-induced Pol II clearing did not operate. Interestingly, at promoters, where Pol II promoter clearance occurs, TFIIH, but not TBP, follows the behavior of Pol II, suggesting that at these genes upon UVB treatment TFIIH is sequestered for DNA repair by the TCR machinery. In agreement, in cells where the TCR factor, the Cockayne Syndrome B protein, was depleted UVB did not induce Pol II and TFIIH clearance at promoters. Thus, our study reveals a UVB induced negative regulatory mechanism that targets Pol II transcription initiation on the large majority of transcribed gene promoters, and a small subset of genes, where Pol II escapes this negative regulation. PMID:25058334

Basis of Miscoding of the DNA Adduct N2,3-Ethenoguanine by Human Y-family DNA Polymerases*

PubMed Central

Zhao, Linlin; Pence, Matthew G.; Christov, Plamen P.; Wawrzak, Zdzislaw; Choi, Jeong-Yun; Rizzo, Carmelo J.; Egli, Martin; Guengerich, F. Peter

2012-01-01

N2,3-Ethenoguanine (N2,3-ϵG) is one of the exocyclic DNA adducts produced by endogenous processes (e.g. lipid peroxidation) and exposure to bioactivated vinyl monomers such as vinyl chloride, which is a known human carcinogen. Existing studies exploring the miscoding potential of this lesion are quite indirect because of the lability of the glycosidic bond. We utilized a 2′-fluoro isostere approach to stabilize this lesion and synthesized oligonucleotides containing 2′-fluoro-N2,3-ϵ-2′-deoxyarabinoguanosine to investigate the miscoding potential of N2,3-ϵG by Y-family human DNA polymerases (pols). In primer extension assays, pol η and pol κ replicated through N2,3-ϵG, whereas pol ι and REV1 yielded only 1-base incorporation. Steady-state kinetics revealed that dCTP incorporation is preferred opposite N2,3-ϵG with relative efficiencies in the order of pol κ > REV1 > pol η ≈ pol ι, and dTTP misincorporation is the major miscoding event by all four Y-family human DNA pols. Pol ι had the highest dTTP misincorporation frequency (0.71) followed by pol η (0.63). REV1 misincorporated dTTP and dGTP with much lower frequencies. Crystal structures of pol ι with N2,3-ϵG paired to dCTP and dTTP revealed Hoogsteen-like base pairing mechanisms. Two hydrogen bonds were observed in the N2,3-ϵG:dCTP base pair, whereas only one appears to be present in the case of the N2,3-ϵG:dTTP pair. Base pairing mechanisms derived from the crystal structures explain the slightly favored dCTP insertion for pol ι in steady-state kinetic analysis. Taken together, these results provide a basis for the mutagenic potential of N2,3-ϵG. PMID:22910910

DNA Polymerase λ Inactivation by Oxidized Abasic Sites&

PubMed Central

Stevens, Adam J.; Guan, Lirui; Bebenek, Katarzyna; Kunkel, Thomas A.; Greenberg, Marc M.

2013-01-01

Base excision repair plays a vital role in maintaining genomic integrity in mammalian cells. DNA polymerase λ is believed to play a backup role to DNA polymerase β in base excision repair. Two oxidized abasic lesions that are produced by a variety of DNA damaging agents, including several antitumor antibiotics, the C4′-oxidized abasic site following Ape1 incision (pC4-AP) and 5′-(2-phosphoryl-1,4-dioxobutane) (DOB), irreversibly inactivate Pol β and Pol λ. The interactions of DOB and pC4-AP with Pol λ are examined in detail using DNA substrates containing these lesions at defined sites. Single turnover kinetic experiments show that Pol λ excises DOB almost 13-times more slowly than a 5′-phosphorylated 2-deoxyribose (dRP). pC4-AP is excised approximately twice as fast as DOB. The absolute rate constants are considerably slower than those reported for Pol β at the respective reactions, suggesting that Pol λ may be an inefficient backup in BER. DOB inactivates Pol λ approximately 3-fold less efficiently than it does Pol β and the difference is attributable to a higher KI (33 ± 7 nM). Inactivation of Pol λ’s lyase activity by DOB also prevents the enzyme from carrying out polymerization following preincubation of the protein and DNA. Mass spectral analysis of GluC digested Pol λ inactivated by DOB shows that Lys324 is modified. There is inferential support that Lys312 may also be modified. Both residues are within the Pol λ lyase active site. Protein modification involves reaction with released but-2-ene-1,4-dial. When acting on pC4-AP, Pol λ achieves approximately 4 turnovers on average before being inactivated. Lyase inactivation by pC4-AP is also accompanied by loss of polymerase activity and mass spectrometry indicates that Lys312 and Lys324 are modified by the lesion. The ability of DOB and pC4-AP to inactivate Pol λ provides additional evidence that these lesions are significant sources of the cytotoxicity of DNA damaging agents that produce them. PMID:23330920

Gammaretroviral pol sequences act in cis to direct polysome loading and NXF1/NXT-dependent protein production by gag-encoded RNA.

PubMed

Bartels, Hanni; Luban, Jeremy

2014-09-12

All retroviruses synthesize essential proteins via alternatively spliced mRNAs. Retrovirus genera, though, exploit different mechanisms to coordinate the synthesis of proteins from alternatively spliced mRNAs. The best studied of these retroviral, post-transcriptional effectors are the trans-acting Rev protein of lentiviruses and the cis-acting constitutive transport element (CTE) of the betaretrovirus Mason-Pfizer monkey virus (MPMV). How members of the gammaretrovirus genus translate protein from unspliced RNA has not been elucidated. The mechanism by which two gammaretroviruses, XMRV and MLV, synthesize the Gag polyprotein (Pr65Gag) from full-length, unspliced mRNA was investigated here. The yield of Pr65Gag from a gag-only expression plasmid was found to be at least 30-fold less than that from an otherwise isogenic gag-pol expression plasmid. A frameshift mutation disrupting the pol open reading frame within the gag-pol expression plasmid did not decrease Pr65Gag production and 398 silent nucleotide changes engineered into gag rendered Pr65Gag synthesis pol-independent. These results are consistent with pol-encoded RNA acting in cis to promote Pr65Gag translation. Two independently-acting pol fragments were identified by screening 17 pol deletion mutations. To determine the mechanism by which pol promoted Pr65Gag synthesis, gag RNA in total and cytoplasmic fractions was quantitated by northern blot and by RT-PCR. The pol sequences caused, maximally, three-fold increase in total or cytoplasmic gag mRNA. Instead, pol sequences increased gag mRNA association with polyribosomes ~100-fold, a magnitude sufficient to explain the increase in Pr65Gag translation efficiency. The MPMV CTE, an NXF1-binding element, substituted for pol in promoting Pr65Gag synthesis. A pol RNA stem-loop resembling the CTE promoted Pr65Gag synthesis. Over-expression of NXF1 and NXT, host factors that bind to the MPMV CTE, synergized with pol to promote gammaretroviral gag RNA loading onto polysomes and to increase Pr65Gag synthesis. Conversely, Gag polyprotein synthesis was decreased by NXF1 knockdown. Finally, overexpression of SRp20, a shuttling protein that binds to NXF1 and promotes NXF1 binding to RNA, also increased gag RNA loading onto polysomes and increased Pr65Gag synthesis. These experiments demonstrate that gammaretroviral pol sequences act in cis to recruit NXF1 and SRp20 to promote polysome loading of gag RNA and, thereby license the synthesis of Pr65Gag from unspliced mRNA.

Segmentation of Polarimetric SAR Images Usig Wavelet Transformation and Texture Features

NASA Astrophysics Data System (ADS)

Rezaeian, A.; Homayouni, S.; Safari, A.

2015-12-01

Polarimetric Synthetic Aperture Radar (PolSAR) sensors can collect useful observations from earth's surfaces and phenomena for various remote sensing applications, such as land cover mapping, change and target detection. These data can be acquired without the limitations of weather conditions, sun illumination and dust particles. As result, SAR images, and in particular Polarimetric SAR (PolSAR) are powerful tools for various environmental applications. Unlike the optical images, SAR images suffer from the unavoidable speckle, which causes the segmentation of this data difficult. In this paper, we use the wavelet transformation for segmentation of PolSAR images. Our proposed method is based on the multi-resolution analysis of texture features is based on wavelet transformation. Here, we use the information of gray level value and the information of texture. First, we produce coherency or covariance matrices and then generate span image from them. In the next step of proposed method is texture feature extraction from sub-bands is generated from discrete wavelet transform (DWT). Finally, PolSAR image are segmented using clustering methods as fuzzy c-means (FCM) and k-means clustering. We have applied the proposed methodology to full polarimetric SAR images acquired by the Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR) L-band system, during July, in 2012 over an agricultural area in Winnipeg, Canada.

Zeitlicher Verlauf der avaskulären Nekrose des Hüftkopfes bei Patienten mit Pemphigus vulgaris.

PubMed

Balighi, Kamran; Daneshpazhooh, Maryam; Aghazadeh, Nessa; Saeidi, Vahide; Shahpouri, Farzam; Hejazi, Pardis; Chams-Davatchi, Cheyda

2016-10-01

Pemphigus vulgaris (PV) wird in der Regel mit systemischen Corticosteroiden und Immunsuppressiva behandelt. Avaskuläre Nekrose (AVN) des Hüftkopfes ist eine gut bekannte schwerere Komplikation einer Corticosteroid-Therapie. Die Charakteristika dieser schweren Komplikation bei PV sind nach wie vor unbekannt. Nicht kontrollierte, retrospektive Untersuchung aller PV-bedingten AVN-Fälle, die in einer iranischen Klinik für bullöse Autoimmunerkrankungen zwischen 1985 und 2013 diagnostiziert wurden. Anhand der Krankenakten von 2321 untersuchten PV-Patienten wurden 45 Fälle (1,93 %) von femoraler AVN identifiziert. Dreißig davon waren Männer. Das mittlere Alter bei der Diagnose der AVN betrug 47,4 ± 14,2 Jahre. Der mittlere Zeitraum zwischen der Diagnose des PV und dem Einsetzen der AVN lag bei 25,3 ± 18,3 Monaten. Mit Ausnahme von acht Fällen (17,8 %) setzte die AVN bei der Mehrheit der Patienten innerhalb von drei Jahren nach Diagnose des PV ein. Die mittlere kumulative Dosis von Prednisolon bei Patienten mit AVN betrug 13.115,8 ± 7041,1 mg. Zwischen der Prednisolon-Gesamtdosis und dem Zeitraum bis zum Einsetzen der AVN bestand eine starke Korrelation (p = 0,001). Bei Patienten mit Alendronateinnahme in der Vorgeschichte war dieser Zeitraum signifikant kürzer (p = 0,01). Die AVN ist eine schwere Komplikation einer Corticosteroid-Behandlung bei Patienten mit PV. Sie wird bei 2 % der Patienten beobachtet und tritt vor allem in den ersten drei Behandlungsjahren auf. Bei Patienten, die höhere Dosen von Prednisolon erhalten, setzt die AVN tendenziell früher ein. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

A cascade amplification strategy based on rolling circle amplification and hydroxylamine amplified gold nanoparticles enables chemiluminescence detection of adenosine triphosphate.

PubMed

Wang, Ping; Zhang, Tonghuan; Yang, Taoyi; Jin, Nan; Zhao, Yanjun; Fan, Aiping

2014-08-07

A highly sensitive and selective chemiluminescent (CL) biosensor for adenosine triphosphate (ATP) was developed by taking advantage of the ATP-dependent enzymatic reaction (ATP-DER), the powerful signal amplification capability of rolling circle amplification (RCA), and hydroxylamine-amplified gold nanoparticles (Au NPs). The strategy relies on the ability of ATP, a cofactor of T4 DNA ligase, to trigger the ligation-RCA reaction. In the presence of ATP, the T4 DNA ligase catalyzes the ligation reaction between the two ends of the padlock probe, producing a closed circular DNA template that initiates the RCA reaction with phi29 DNA polymerase and dNTP. Therein, many complementary copies of the circular template can be generated. The ATP-DER is eventually converted into a detectable CL signal after a series of processes, including gold probe hybridization, hydroxylamine amplification, and oxidative gold metal dissolution coupled with a simple and sensitive luminol CL reaction. The CL signal is directly proportional to the ATP level. The results showed that the detection limit of the assay is 100 pM of ATP, which compares favorably with those of other ATP detection techniques. In addition, by taking advantage of ATP-DER, the proposed CL sensing system exhibits extraordinary specificity towards ATP and could distinguish the target molecule ATP from its analogues. The proposed method provides a new and versatile platform for the design of novel DNA ligation reaction-based CL sensing systems for other cofactors. This novel ATP-DER based CL sensing system may find wide applications in clinical diagnosis as well as in environmental and biomedical fields.

Implementing a C++ Version of the Joint Seismic-Geodetic Algorithm for Finite-Fault Detection and Slip Inversion for Earthquake Early Warning

NASA Astrophysics Data System (ADS)

Smith, D. E.; Felizardo, C.; Minson, S. E.; Boese, M.; Langbein, J. O.; Guillemot, C.; Murray, J. R.

2015-12-01

The earthquake early warning (EEW) systems in California and elsewhere can greatly benefit from algorithms that generate estimates of finite-fault parameters. These estimates could significantly improve real-time shaking calculations and yield important information for immediate disaster response. Minson et al. (2015) determined that combining FinDer's seismic-based algorithm (Böse et al., 2012) with BEFORES' geodetic-based algorithm (Minson et al., 2014) yields a more robust and informative joint solution than using either algorithm alone. FinDer examines the distribution of peak ground accelerations from seismic stations and determines the best finite-fault extent and strike from template matching. BEFORES employs a Bayesian framework to search for the best slip inversion over all possible fault geometries in terms of strike and dip. Using FinDer and BEFORES together generates estimates of finite-fault extent, strike, dip, preferred slip, and magnitude. To yield the quickest, most flexible, and open-source version of the joint algorithm, we translated BEFORES and FinDer from Matlab into C++. We are now developing a C++ Application Protocol Interface for these two algorithms to be connected to the seismic and geodetic data flowing from the EEW system. The interface that is being developed will also enable communication between the two algorithms to generate the joint solution of finite-fault parameters. Once this interface is developed and implemented, the next step will be to run test seismic and geodetic data through the system via the Earthworm module, Tank Player. This will allow us to examine algorithm performance on simulated data and past real events.

Early-life house dust mite allergens, childhood mite sensitization, and respiratory outcomes.

PubMed

Casas, L; Sunyer, J; Tischer, C; Gehring, U; Wickman, M; Garcia-Esteban, R; Lehmann, I; Kull, I; Reich, A; Lau, S; Wijga, A; Antó, J M; Nawrot, T S; Heinrich, J; Keil, T; Torrent, M

2015-07-01

Exposure to indoor allergens during early life may play a role in the development of the immune system and inception of asthma. To describe the house dust mite (HDM) allergen concentrations in bedroom dust during early life and to evaluate its associations with HDM sensitization, wheezing, and asthma, from birth to school age, in 5 geographically spread European birth cohorts. We included 4334 children from INMA-Menorca (Spain), BAMSE (Sweden), LISAplus and MAS (Germany), and PIAMA-NHS (the Netherlands). Dust samples were collected from bedrooms during early life and analyzed for Dermatophagoides pteronyssinus (Der p1) and Dermatophagoides farinae (Der f1). HDM concentrations were divided into four categories. Sensitization was determined by specific IgE. Wheezing and asthma information up to 8/10 years was collected through questionnaires. We performed mixed-effects logistic regression models and expressed associations as odds ratios with 95% confidence intervals. House dust mite concentrations varied across cohorts. Mean allergen concentrations were highest in INMA-Menorca (geometric mean (GM) Der p1 = 3.3 μg/g) and LISAplus (GM Der f1 = 2.1 μg/g) and lowest in BAMSE (GM Der p1 = 0.1 μg/g, Der f1 = 0.3 μg/g). Moderate and high HDM concentrations were significantly (P-values < 0.05) associated with 50-90% higher prevalence of HDM sensitization. No significant associations were observed with respiratory outcomes. Our study based on geographically spread regions, a large sample size, and a wide range of allergen concentration shows that HDM allergen concentrations vary across regions and that exposure during early life plays a role in the development of allergic sensitization but not in the development of respiratory outcomes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An ATP-dependent ligase with substrate flexibility involved in assembly of the peptidyl nucleoside antibiotic polyoxin

USDA-ARS?s Scientific Manuscript database

Polyoxin (POL) is an unusual nucleoside antibiotic, in which peptidyl moiety and nucleoside skeleton are linked by an amide bond. However, their biosynthesis remains poorly understood. Here, we report the deciphering of PolG as an ATP-dependent ligase responsible for the assembly of POL. A polG muta...

Bay Ridge Gardens - Mixed-Humid Affordable Multifamily Housing Deep Energy Retrofit

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

Lyons, J.; Moore, M.; Thompson, M.

2013-08-01

Under this project, Newport Partners (as part of the BA-PIRC research team) evaluated the installation, measured performance, and cost-effectiveness of efficiency upgrade measures for a tenant-in-place DER at the Bay Ridge multifamily (MF) development in Annapolis, Maryland. The design and construction phase of the Bay Ridge project was completed in August 2012. This report summarizes system commissioning, short-term test results, utility bill data analysis, and analysis of real-time data collected over a one-year period after the retrofit was complete. The Bay Ridge project is comprised of a 'base scope' retrofit which was estimated to achieve a 30%+ savings (relative tomore » pre-retrofit) on 186 apartments, and a 'DER scope' which was estimated to achieve 50% savings (relative to pre-retrofit) on a 12-unit building. The base scope was applied to the entire apartment complex, except for one 12-unit building which underwent the DER scope. A wide range of efficiency measures was applied to pursue this savings target for the DER building, including improvements/replacements of mechanical equipment and distribution systems, appliances, lighting and lighting controls, the building envelope, hot water conservation measures, and resident education. The results of this research build upon the current body of knowledge of multifamily retrofits. Towards this end, the research team has collected and generated data on the selection of measures, their estimated performance, their measured performance, and risk factors and their impact on potential measures.« less

Refolding Active Human DNA Polymerase ν from Inclusion Bodies

PubMed Central

Arana, Mercedes E.; Powell, Gary K.; Edwards, Lori L.; Kunkel, Thomas A.; Petrovich, Robert M.

2017-01-01

Human DNA polymerase ν (Pol ν) is a conserved family A DNA polymerase of uncertain biological function. Physical and biochemical characterization aimed at understanding Pol ν function is hindered by the fact that, when over-expressed in E. coli, Pol ν is largely insoluble, and the small amount of soluble protein is difficult to purify. Here we describe the use of high hydrostatic pressure to refold Pol ν from inclusion bodies, in soluble and active form. The refolded Pol ν has properties comparable to those of the small amount of Pol ν that was purified from the soluble fraction. The approach described here may be applicable to other DNA polymerases that are expressed as insoluble inclusion bodies in E. coli. PMID:19853037

Einsatz molekularer Methoden für Starterkulturen

NASA Astrophysics Data System (ADS)

Ehrmann, Matthias A.; Pavlovic, Melanie

Unter Starterkulturen versteht man Mikroorganismen (Bakterien, Hefen, Pilze), die pflanzlichen bzw. tierischen Rohstoffen zur gezielten Veränderung ihrer chemischen Zusammensetzung zugesetzt werden. Sie dienen im Wesentlichen der Aromabildung, der Strukturveränderung und der Konservierung der Lebensmittel und werden aufgrund spezieller, funktioneller Eigenschaften selektiert. Die Zugabe von Starterkulturen erfolgt in der Regel in relativ hohen Keimzahlen in Form von Rein- oder Mischkulturen. Die zum Einsatz kommenden Mikroorganismen sind ebenso zahlreich wie die daraus resultierenden Produkte und reichen von der Fermentation von Milchprodukten, Fleisch und Gemüse durch Milchsäurebakterien über die Essigsäureherstellung bis hin zum Einsatz von Hefen in der Brau- und Weinindustrie. Hieraus ergibt sich auch eine zunehmende Bedeutung schneller und zuverlässiger Methoden zur taxonomischen Identifizierung, aber auch zur Charakterisierung des genetischen Potenzials der jeweiligen Starterkulturen.

Satellitenbewegung, band III: Natiirliche und gesteuerte bewegung.

NASA Astrophysics Data System (ADS)

Jochim, E. F.

2014-12-01

Im dritten Band der Satellitenbewegung werden in fortlaufender Nummerierung einige für Untersuchungen der Bewegung der künstlichen Satelliten wichtige Grundlagen der Astrodynamik mit ausführlichen mathematischen Formelsystemen behandelt. Dazu zählen die unterschiedlichen Aspekte der Bewegung der natürlichen Himmelskörper, die Steuerung und Kontrolle von künstlichen Objekten, und insbesondere die für eine Satellitenbahnanalyse wichtigen physikalischen Beeinflussungen einer Satellitenbewegung. Mathematisch entscheidend ist die Wahl geeigneter Bahnparameter, die ein bestimmtes Bewegungsproblem widerspruchsfrei und singularitätenfrei zu behandeln gestatten. Für die Behandlung routinemäßiger Aufgabenstellungen der Satellitenbewegung, in erster Linie einer präzisen Bahnbestimmung und Bahnverbesserung, kann auf eine Fülle von lehrbuchartigen Monographien verwiesen werden, so dass diese Problematik in der vorliegenden Arbeit nur angedeutet werden soll.

Modellierung des Einflusses der Landnutzung auf die Hochwasserentstehung in der Mesoskala

NASA Astrophysics Data System (ADS)

Niehoff, Daniel

2001-10-01

Seit 1990 waren mehrere der großen Flussgebiete Mitteleuropas wiederholt von extremen Hochwassern betroffen. Da sowohl die Landoberfläche als auch die Flusssysteme weiter Teile Mitteleuropas in der Vergangenheit weitreichenden Eingriffen ausgesetzt gewesen sind, wird bei der Suche nach den Ursachen für diese Häufung von Extremereignissen auch die Frage nach der Verantwortung des Menschen hierfür diskutiert. Gewässerausbau, Flächenversiegelung, intensive landwirtschaftliche Bodenbearbeitung, Flurbereinigung und Waldschäden sind nur einige Beispiele und Folgen der anthropogenen Eingriffe in die Landschaft. Aufgrund der Vielfalt der beteiligten Prozesse und deren Wechselwirkungen gibt es allerdings bislang nur Schätzungen darüber, wie sehr sich die Hochwassersituation hierdurch verändert hat. Vorrangiges Ziel dieser Arbeit ist es, mit Hilfe eines hydrologischen Modells systematisch darzustellen, in welcher Weise, in welcher Größenordnung und unter welchen Umständen die Art der Landnutzung auf die Hochwasserentstehung Einfluss nimmt. Dies wird anhand exemplarischer Modellanwendungen in der hydrologischen Mesoskala untersucht. Zu diesem Zweck wurde das deterministische und flächendifferenzierte hydrologische Modell wasim-eth ausgewählt, das sich durch eine ausgewogene Mischung aus physikalisch begründeten und konzeptionellen Ansätzen auszeichnet. Das Modell wurde im Rahmen dieser Arbeit um verschiedene Aspekte erweitert, die für die Charakterisierung des Einflusses der Landnutzung auf die Hochwasserentstehung wichtig sind: (1) Bevorzugtes Fließen in Makroporen wird durch eine Zweiteilung des Bodens in Makroporen und Bodenmatrix dargestellt, die schnelle Infiltration und Perkolation jenseits der hydraulischen Leitfähigkeit der Bodenmatrix ermöglicht. (2) Verschlämmung äußert sich im Modell abhängig von Niederschlagsintensität und Vegetationsbedeckungsgrad als Verschlechterung der Infiltrationsbedingungen an der Bodenoberfläche. (3) Das heterogene Erscheinungsbild bebauter Flächen mit einer Mischung aus versiegelten Bereichen und Freiflächen wird berücksichtigt, indem jede Teilfläche je nach Versiegelungsgrad in einen unversiegelten Bereich und einen versiegelten Bereich mit Anschluss an die Kanalisation aufgeteilt wird. (4) Dezentraler Rückhalt von Niederschlagswasser kann sowohl für natürliche Mulden als auch für gezielt angelegte Versickerungsmulden mit definierten Infiltrationsbedingungen simuliert werden. Das erweiterte Modell wird exemplarisch auf drei mesoskalige Teileinzugsgebiete des Rheins angewandt. Diese drei Gebiete mit einer Fläche von zwischen 100 und 500 km² wurden im Hinblick darauf ausgewählt, dass jeweils eine der drei Hauptlandnutzungskategorien Bebauung, landwirtschaftliche Nutzung oder Wald dominiert. Für die drei Untersuchungsgebiete sind räumlich explizite Landnutzungs- und Landbedeckungsszenarien entworfen worden, deren Einfluss auf die Hochwasserentstehung mit Hilfe des erweiterten hydrologischen Modells simuliert wird. Im Einzelnen werden die Auswirkungen von Verstädterung, Maßnahmen zur Niederschlagsversickerung in Siedlungsgebieten, Stilllegung agrarisch genutzter Flächen, veränderter landwirtschaftlicher Bodenbearbeitung, Aufforstung sowie von Sturmschäden in Wäldern untersucht. Diese Eingriffe beeinflussen die Interzeption von Niederschlag, dessen Infiltration, die oberflächennahen unterirdischen Fließprozesse sowie, zum Beispiel im Fall der Kanalisation, auch die Abflusskonzentration. Die hydrologischen Simulationen demonstrieren, dass die Versiegelung einer Fläche den massivsten Eingriff in die natürlichen Verhältnisse darstellt und deshalb die stärksten (negativen) Veränderungen der Hochwassersituation hervorbringt. Außerdem wird deutlich, dass eine bloße Änderung des Interzeptionsvermögens zu keinen wesentlichen Veränderungen führt, da die Speicherkapazität der Pflanzenoberflächen im Verhältnis zum Volumen hochwasserauslösender Niederschläge eher klein ist. Stärkere Veränderungen ergeben sich hingegen aus einer Änderung der Infiltrationsbedingungen. Die Grenzen der entwickelten Methodik zeigen sich am deutlichsten bei der Simulation veränderter landwirtschaftlicher Bewirtschaftungsmethoden, deren mathematische Beschreibung und zahlenmäßige Charakterisierung aufgrund der Komplexität der beteiligten Prozesse mit großen Unsicherheiten behaftet ist. Die Modellierungsergebnisse belegen darüber hinaus, dass pauschale Aussagen zum Einfluss der Landnutzung auf die Hochwasserentstehung aufgrund der entscheidenden Bedeutung der klimatischen und physiographischen Randbedingungen unzulässig sind. Zu den klimatischen Randbedingungen zählen sowohl Niederschlagsintensität und -dauer als auch die Feuchtebedingungen vor einem hochwasserauslösenden Niederschlag. Die physiographischen Randbedingungen sind von der geomorphologischen und geologischen Ausstattung des Gebiets vorgegeben. Weiterhin muss der räumliche und zeitliche Maßstab, über den Aussagen getroffen werden, klar definiert sein, da sich mit steigender Einzugsgebietsgröße die relative Bedeutung sowohl der verschiedenen Niederschlagstypen als auch der physiographischen Eigenschaften verschiebt. Dies wird in der vorliegenden Arbeit im Gegensatz zu vielen anderen Untersuchungen konsequent berücksichtigt. In Abhängigkeit von Randbedingungen und räumlichen Maßstab sind aufgrund der gewonnen Erkenntnisse folgende Aussagen zum Einfluss von Landnutzungsänderungen auf die Hochwasserentstehung möglich: (1) Für intensive konvektive Niederschlagsereignisse mit tendenziell geringer Vorfeuchte ist der Einfluss der Landnutzung größer als für langanhaltende advektive Niederschläge geringer Intensität, da im ersten Fall veränderte Infiltrationsbedingungen stärker zum Tragen kommen als bei kleinen Niederschlagsintensitäten. (2) In kleinen Einzugsgebieten, wo kleinräumige Konvektivzellen zu Hochwassern führen können, ist der Einfluss der Landnutzung dementsprechend größer als in großen Flussgebieten wie dem Rheingebiet, wo vor allem langanhaltende advektive Ereignisse (unter Umständen verbunden mit Schneeschmelze) relevant sind. (3) In Gebieten mit guten Speichereigenschaften wie mächtigen, gut durchlässigen Böden und gut durchlässigem Gesteinsuntergrund ist der Einfluss der Landnutzung größer als in Gebieten mit geringmächtigen Böden und geringdurchlässigem Festgestein. Dies ist darin begründet, dass in Gebieten mit guten Speichereigenschaften bei einer Verschlechterung der Infiltrationsbedingungen mehr Speicherraum für Niederschlag verloren geht als in anderen Gebieten. Since 1990, several of the large European river basins were affected repeatedly by extreme floods. As both the landscape and the river systems in large parts of Central Europe have undergone major changes in the past, during the search for the causes of this accumulation of extreme events also the impact of human activities on flooding has been discussed. River training, surface sealing, intensive agricultural land-use, consolidation of farmland, and damages to forests are only some examples and consequences of the anthropogenic interferences with the landscape. But due to the diversity of the processes and factors involved, by now it can only be estimated how far the flood situation has changed by these interferences. Therefore, the main target of this thesis is to describe systematically in which way, to what extent and under which circumstances the land-use exerts an influence on storm-runoff generation and subsequently the discharge of rivers. This is investigated by means of exemplary model applications at the hydrological meso-scale. For this task, the deterministic and distributed hydrological model wasim-eth was chosen due to its well-balanced mixture of physically-based and conceptual approaches. In the framework of this thesis, the model has been extended in order to cope with several phenomena which are important when aiming at a characterization of the influence of land-use on flood generation: (1) Preferential flow in macropores is treated by a division of the soil into macropores and a soil matrix. This so-called double-porosity approach allows for fast infiltration and percolation beyond the hydraulic conductivity of the soil matrix. (2) Siltation expresses itself within the model as a deterioration of infiltration conditions at the soil surface, depending on precipitation intensity and the degree of vegetation covering. (3) The heterogeneous appearance of built-up areas, consisting of both sealed areas and pervious areas, is taken into account by dividing each partial area into an unsealed part and a sealed part which is connected to the sewer system. (4) Decentralized storage can be simulated for natural depressions as well as for specific infiltration measures with defined infiltration conditions. The extended model is exemplarily applied to three meso-scale tributaries of the Rhine river. These three catchments with an area of between 100 and 500 km² were chosen with regard to their prevailing land-use, one of them being heavily urbanized, one dominated by agricultural use, and one being mainly forested. For these three catchments, spatially explicit land-use and land-cover scenarios were developed. The impact of these scenarios on storm-runoff generation is being simulated using the extended hydrological model. In this context, namely urbanization, infiltration measures in settlement areas, conversion of farmland to set-aside areas, altered agricultural management practices, affor estation and storm damages in forests are taken into account. These changes influence the interception of rainfall, its infiltration into the soil, the subsurface flow processes next to the soil surface as well as, for example in the case of sewer systems, also runoff concentration. The hydrological simulations demonstrate that sealing of the soil surface is the most intensive intervention in the natural conditions among the ones which are mentioned above. Therefore it results in the strongest (negative) changes of the flooding situation in a catchment. In addition to that, the simulations show that a simple alteration in the interception capacity does not yield significant changes in catchment response, because the storage capacity of vegetation surfaces is rather low compared to the volume of storm events which normally lead to significant floods. More pronounced changes arise from modifications in the infiltration conditions. The limits of the methodology which was chosen for this thesis become obvious when simulating altered agricultural management practices. Due the complexity of the processes involved, mathematical description and parameterization is difficult and therefore afflicted with high uncertainty. In addition to that, the modelling results prove that global statements on the influence of land-use on flood generation are illegitimate because of the paramount importance of the climatic and physiographic boundary conditions. Climatic boundary conditions are precipitation intensity and duration as well as the moisture conditions before a storm event. The physiographic boundary counditions are given by the geomorphological and geological catchment properties. Furthermore, with increasing scale there is a shift in the relative importance of the different types of rainfall as well as the different geophysical catchment properties. Therefore, the spatial and temporal scale for which the results are valid have to be clearly defined. This is taken into account consequently within this thesis - in contrast to many other studies on this topic. Depending on boundary conditions and spatial scale, the findings allow the following statements regarding the influence of land-use changes on storm-runoff generation: (1) For intensive convective storm events with generally low antecedent soil moisture, the influence of land-use is greater than for long-lasting advective storm events with low rainfall intensities, because in the first case changes in the infiltration conditions are more important than during times of low precipitation intensities. (2) In small catchments, where small-scale convective cells can lead to a flood, the influence of land-use is accordingly greater than in large river basins like the Rhine basin, where long-lasting advective rainfalls (possibly in combination with snowmelt) are relevant. (3) In areas with good storage conditions like thick, permeable soils and pervious rock underneath, the influence of land-use is greater than in areas with thin soils and only slightly permeable bedrock. This is due to the fact that in case of deteriorating infiltration conditions, more storage space for precipitation is lost in areas with good storage conditions than in other areas. siehe auch: http://opus.kobv.de/ubp/volltexte/2005/398/

MultiFocus Polarization Microscope (MF-PolScope) for 3D polarization imaging of up to 25 focal planes simultaneously

PubMed Central

Abrahamsson, Sara; McQuilken, Molly; Mehta, Shalin B.; Verma, Amitabh; Larsch, Johannes; Ilic, Rob; Heintzmann, Rainer; Bargmann, Cornelia I.; Gladfelter, Amy S.; Oldenbourg, Rudolf

2015-01-01

We have developed an imaging system for 3D time-lapse polarization microscopy of living biological samples. Polarization imaging reveals the position, alignment and orientation of submicroscopic features in label-free as well as fluorescently labeled specimens. Optical anisotropies are calculated from a series of images where the sample is illuminated by light of different polarization states. Due to the number of images necessary to collect both multiple polarization states and multiple focal planes, 3D polarization imaging is most often prohibitively slow. Our MF-PolScope system employs multifocus optics to form an instantaneous 3D image of up to 25 simultaneous focal-planes. We describe this optical system and show examples of 3D multi-focus polarization imaging of biological samples, including a protein assembly study in budding yeast cells. PMID:25837112

Was leistet ein Sportler? Kraft, Leistung und Energie im Muskel

NASA Astrophysics Data System (ADS)

Thaller, Sigrid; Mathelitsch, Leopold

2006-01-01

Der Leistungsbegriff ist im Sport weiter gefasst als in der Physik. In beiden Fällen liegt der Fokus jedoch auf einer pro Zeiteinheit erfolgten Energieumsetzung. Allerdings gibt die rein physikalische Leistung nicht immer Auskunft über den Energieumsatz der Muskeln. Die Muskelkraft hängt von der Kontraktionsgeschwindigkeit des Muskels ab. Ein Muskel verhält sich also anders als eine Feder. Für den Hochleistungssport müssen die Energieumsätze der Muskeln durch spezielle Trainings- und Nahrungsprogramme optimiert werden.

Sterblichkeit: der paradoxe Kunstgriff des Lebens - Eine Betrachtung vor dem Hintergrund der modernen Biologie

NASA Astrophysics Data System (ADS)

Verbeek, Bernhard

Leben gibt es auf der Erde seit fast 4 Mio. Jahren, trotz allen Katastrophen. Die Idee des Lebens scheint unsterblich. Der Tod aber offenbar auch. Jedes Lebewesen ist davon bedroht, ja für Menschen und andere "höhere“ Lebewesen ist er im Lebensprogramm eingebaut - todsicher. Diese Tatsache ist alles andere als selbstverständlich. Ist sie überhaupt kompatibel mit dem Prinzip der Evolution, nach dem der am besten Angepasste überlebt?

Stenting und technische Stentumgebung

NASA Astrophysics Data System (ADS)

Hoffstetter, Marc; Pfeifer, Stefan; Schratzenstaller, Thomas; Wintermantel, Erich

In hoch entwickelten Industrieländern stehen laut Weltgesundheitsorganisation (WHO) Herz-Kreislauf-Erkrankungen und speziell die Koronare Herzkrankheit (KHK) an erster Stelle der Todesursachen. In Deutschland betrug die Zahl der erfassten, an KHK erkrankten Personen ohne Berücksichtigung der Dunkelziffer allein im Jahre 2001 über 473.000. Die KHK war im Jahre 2003 mit 92.673 erfassten Todesfällen immer noch die häufigste Todesursache, obgleich in Deutschland die Häufigkeit der Koronarinterventionen zur Behandlung der KHK zwischen 1984 und 2003 um fast das 80fache von 2.809 auf 221.867 Eingriffe pro Jahr gestiegen ist [1]. Neben der hohen Zahl an Todesfällen haben die betroffenen Personen durch chronische Schmerzen und eingeschränkte körperliche Leistungsfähigkeit zusätzlich eine starke Beeinträchtigung der Lebensqualität [2].In Folge dessen wird die erkrankte Person häufig zum Pflegefall was neben den gesundheitlichen Aspekten auch eine sozioökonomische Komponente in Form der fehlenden Arbeitskraft und den auftretenden Pflegekosten nach sich zieht. Die Kosten für die Behandlung der KHK in Deutschland beliefen sich im Jahre 2002 laut Statistischem Bundesamt auf rund 6,9 Mrd. €. Verglichen mit ähnlichen Zahlen der USA dürfte sich der entstandene Schaden für die deutsche Volkswirtschaft im zwei- bis dreistelligen Milliardenbereich bewegen [3].

Characterisation of tropomyosin and paramyosin as vaccine candidate molecules for the poultry red mite, Dermanyssus gallinae.

PubMed

Wright, Harry W; Bartley, Kathryn; Huntley, John F; Nisbet, Alasdair J

2016-10-12

Dermanyssus gallinae is the most economically important haematophagous ectoparasite in commercial egg laying flocks worldwide. It infests the hens during the night where it causes irritation leading to restlessness, pecking and in extreme cases anaemia and increased cannibalism. Due to an increase in the occurrence of acaricide-resistant D. gallinae populations, new control strategies are required and vaccination may offer a sustainable alternative to acaricides. In this study, recombinant forms of D. gallinae tropomyosin (Der g 10) and paramyosin (Der g 11) were produced, characterised and tested as vaccine candidate molecules. The D. gallinae paramyosin (Der g 11) coding sequence was characterised and recombinant versions of Der g 11 and D. gallinae tropomyosin (Der g 10) were produced. Hens were immunised with the recombinant proteins and the resulting antibodies were fed to D. gallinae and mite mortality evaluated. Sections of mites were probed with anti- Der g 11 and Der g 10 antibodies to identify the tissue distribution of these protein in D. gallinae. The entire coding sequence of Der g 11 was 2,622 bp encoding 874 amino acid residues. Immunohistochemical staining of mite sections revealed that Der g 10 and Der g 11 were located throughout D. gallinae tissues. In phylogenetic analyses of these proteins both clustered with orthologues from tick species rather than with orthologues from astigmatid mites. Antibodies raised in hens against recombinant forms of these proteins significantly increased D. gallinae mortality, by 19 % for Der g 10 (P < 0.001) and by 23 % for Der g 11 (P = 0.009) when fed to the mites using an in vitro feeding device. This study has shown that Der g 10 and Der g 11 were located ubiquitously throughout D. gallinae and that antibodies raised against recombinant versions of these proteins can be used to significantly increase D. gallinae mortality in an in vitro feeding assay. When comparing archived data for all recombinant and native proteins assessed as vaccines using this in vitro feeding assay, Der g 10 and Der g 11 ranked highly and performed better than some of the pools of native proteins.

Spaceborne Hybrid Quad-Pol SAR Range Ambiguity Analysis and Simulations

NASA Astrophysics Data System (ADS)

Yang, Shilin; Li, Yang; Zhang, Jingjing; Hong, Wen

2014-11-01

The higher levels of range ambiguities in the cross-polarized measurement channels are the primary limitations for the matched quad-pol (e.g., HH, VV, VH, and HV) spaceborne synthetic aperture radar (SAR) systems. These ambiguities severely constrain the useful range of incident angles and the swath widths particularly at larger incidence. Adopting hybridpolarimetric architecture can remarkably reduce these ambiguities. In this paper, we analyse and develop the expression of range ambiguity to signal ratio (RASR) in the hybrid-polarimetric architecture. Simulations are made to testify this novel architecture’s advantage in the improvement of range ambiguities. The system operating parameters are derived from NASA’s DESDynl mission. In addition, we used the second order moments of polarimetric covariance matrices to depict target or the environment which are more precisely.

Spaceborne Hybrid Quad-Pol SAR Range Ambiguity Analysis and Simulations

NASA Astrophysics Data System (ADS)

Yang, Shilin; Li, Yang; Zhang, Jingjing; Hong, Wen

2014-11-01

The higher levels of range ambiguities in the cross- polarized measurement channels are the primary limitations for the matched quad-pol (e.g., HH, VV, VH, and HV) spaceborne synthetic aperture radar (SAR) systems. These ambiguities severely constrain the useful range of incident angles and the swath widths particularly at larger incidence. Adopting hybrid- polarimetric architecture can remarkably reduce these ambiguities. In this paper, we analyse and develop the expression of range ambiguity to signal ratio (RASR) in the hybrid-polarimetric architecture. Simulations are made to testify this novel architecture's advantage in the improvement of range ambiguities. The system operating parameters are derived from NASA's DESDynl mission. In addition, we used the second order moments of polarimetric covariance matrices to depict target or the environment which are more precisely.

A Chandra Survey of high-redshift (0.7 < z < 0.8) clusters selected in the 100 deg^2 SPT-Pol Deep Field

NASA Astrophysics Data System (ADS)

Garmire, Gordon

2016-09-01

We propose to observe a complete sample of 10 galaxy clusters at 1e14 < M500 < 5e14 and 0.7 < z < 0.8. These systems were selected from the 100 deg^2 deep field of the SPT-Pol SZ survey. This survey are has significant complementary data, including uniform depth ATCA, Herschel, Spitzer, and DES imaging, enabling a wide variety of astrophysical and cosmological studies. This sample complements the successful SPT-XVP survey, which has a broad redshift range and a narrow mass range, by including clusters over a narrow redshift range and broad mass range. These systems are such low mass and high redshift that they will not be detected in the eRosita all-sky survey.

Die Baukastensystematik in der Fördertechnik

NASA Astrophysics Data System (ADS)

Sebulke, Johannes

In der Fördertechnik wird kaum ein größerer Einsatzfall so dem anderen gleichen, dass man zwei Anlagen nach denselben Zeichnungen fertigen kann. Konstruktionszeiten, Rüst- und Umstellungszeiten der Fertigung sind hoch; der Kunde muss bei Einzelanfertigung lange Lieferzeiten in Kauf nehmen. In der Fördertechnik haben sich daher Baukastenprinzip, Standardisierung und die Konstruktion von Erzeugnisreihen weitgehend durchgesetzt.

Kontinuierliche Wanddickenbestimmung und Visualisierung des linken Herzventrikels

NASA Astrophysics Data System (ADS)

Dornheim, Lars; Hahn, Peter; Oeltze, Steffen; Preim, Bernhard; Tönnies, Klaus D.

Zur Bestimmung von Defekten in der Herztätigkeit kann die Veränderung der Wanddicke des linken Ventrikels in zeitlichen MRTAufnahmesequenzen gemessen werden. Derzeit werden für diese Bestimmung im allgemeinen nur die aufwändig manuell erstellte Segmentierungen der Endsystole und Enddiastole benutzt. Wir stellen ein bis auf die Startpunktinitialisierung automatisches Verfahren zur Bestimmung der Wanddicke des linken Ventrikels und ihrer Veränderung vor, das auf einer vollständigen Segmentierung der Herzwand in allen Zeitschritten durch ein dynamisches dreidimensionales Formmodell (Stabiles Feder-Masse-Modell) basiert. Dieses Modell nutzt bei der Segmentierung neben der Grauwertinformation eines Zeitschrittes auch die Segmentierungen der anderen Zeitschritte und ist so aufgebaut, dass die Wanddicken direkt gemessen und visualisiert werden können. Auf diese Weise werden die lokalen Wanddickenextrema über den gesamten Aufnahmezeitraum detektiert, auch wenn sie nicht in die Endsystole bzw. -diastole fallen. Das Verfahren wurde auf sechs 4D-Kardio-MRT-Datensätzen evaluiert und stellte sich als sehr robust bzgl. der einzig nötigen Interaktion heraus.

DNA polymerase gamma inhibition by vitamin K3 induces mitochondria-mediated cytotoxicity in human cancer cells.

PubMed

Sasaki, Ryohei; Suzuki, Yoko; Yonezawa, Yuko; Ota, Yosuke; Okamoto, Yoshiaki; Demizu, Yusuke; Huang, Peng; Yoshida, Hiromi; Sugimura, Kazuro; Mizushina, Yoshiyuki

2008-05-01

Among the vitamin K (VK) compounds, VK3 exhibits distinct cytotoxic activity in cancer cells and is thought to affect redox cycling; however, the underlying mechanisms remain unclear. Here we demonstrate that VK3 selectively inhibits DNA polymerase (pol) gamma, the key enzyme responsible for mitochondrial DNA replication and repair. VK3 at 30 microM inhibited pol gamma by more than 80%, caused impairment of mitochondrial DNA replication and repair, and induced a significant increase in reactive oxygen species (ROS), leading to apoptosis. At a lower concentration (3 microM), VK3 did not cause a significant increase in ROS, but was able to effectively inhibit cell proliferation, which could be reversed by supplementing glycolytic substrates. The cytotoxic action of VK3 was independent of p53 tumor suppressor gene status. Interestingly, VK3 only inhibited pol gamma but did not affect other pol including human pol alpha, pol beta, pol delta, and pol epsilon. VK1 and VK2 exhibited no inhibitory effect on any of the pol tested. These data together suggest that the inhibition of pol gamma by VK3 is relatively specific, and that this compound seems to exert its anticancer activity by two possible mechanisms in a concentration-dependent manner: (1) induction of ROS-mediated cell death at high concentrations; and (2) inhibition of cell proliferation at lower concentrations likely through the suppression of mitochondrial respiratory function. These findings may explain various cytotoxic actions induced by VK3, and may pave the way for the further use of VK3.

Corresponding-states laws for protein solutions.

PubMed

Katsonis, Panagiotis; Brandon, Simon; Vekilov, Peter G

2006-09-07

The solvent around protein molecules in solutions is structured and this structuring introduces a repulsion in the intermolecular interaction potential at intermediate separations. We use Monte Carlo simulations with isotropic, pair-additive systems interacting with such potentials. We test if the liquid-liquid and liquid-solid phase lines in model protein solutions can be predicted from universal curves and a pair of experimentally determined parameters, as done for atomic and colloid materials using several laws of corresponding states. As predictors, we test three properties at the critical point for liquid-liquid separation: temperature, as in the original van der Waals law, the second virial coefficient, and a modified second virial coefficient, all paired with the critical volume fraction. We find that the van der Waals law is best obeyed and appears more general than its original formulation: A single universal curve describes all tested nonconformal isotropic pair-additive systems. Published experimental data for the liquid-liquid equilibrium for several proteins at various conditions follow a single van der Waals curve. For the solid-liquid equilibrium, we find that no single system property serves as its predictor. We go beyond corresponding-states correlations and put forth semiempirical laws, which allow prediction of the critical temperature and volume fraction solely based on the range of attraction of the intermolecular interaction potential.

FF483–484 motif of human Polη mediates its interaction with the POLD2 subunit of Polδ and contributes to DNA damage tolerance

PubMed Central

Baldeck, Nadège; Janel-Bintz, Régine; Wagner, Jérome; Tissier, Agnès; Fuchs, Robert P.; Burkovics, Peter; Haracska, Lajos; Despras, Emmanuelle; Bichara, Marc; Chatton, Bruno; Cordonnier, Agnès M.

2015-01-01

Switching between replicative and translesion synthesis (TLS) DNA polymerases are crucial events for the completion of genomic DNA synthesis when the replication machinery encounters lesions in the DNA template. In eukaryotes, the translesional DNA polymerase η (Polη) plays a central role for accurate bypass of cyclobutane pyrimidine dimers, the predominant DNA lesions induced by ultraviolet irradiation. Polη deficiency is responsible for a variant form of the Xeroderma pigmentosum (XPV) syndrome, characterized by a predisposition to skin cancer. Here, we show that the FF483–484 amino acids in the human Polη (designated F1 motif) are necessary for the interaction of this TLS polymerase with POLD2, the B subunit of the replicative DNA polymerase δ, both in vitro and in vivo. Mutating this motif impairs Polη function in the bypass of both an N-2-acetylaminofluorene adduct and a TT-CPD lesion in cellular extracts. By complementing XPV cells with different forms of Polη, we show that the F1 motif contributes to the progression of DNA synthesis and to the cell survival after UV irradiation. We propose that the integrity of the F1 motif of Polη, necessary for the Polη/POLD2 interaction, is required for the establishment of an efficient TLS complex. PMID:25662213

Roles of PCNA ubiquitination and TLS polymerases κ and η in the bypass of methyl methanesulfonate-induced DNA damage

PubMed Central

Wit, Niek; Buoninfante, Olimpia Alessandra; van den Berk, Paul C.M.; Jansen, Jacob G.; Hogenbirk, Marc A.; de Wind, Niels; Jacobs, Heinz

2015-01-01

Translesion synthesis (TLS) provides a highly conserved mechanism that enables DNA synthesis on a damaged template. TLS is performed by specialized DNA polymerases of which polymerase (Pol) κ is important for the cellular response to DNA damage induced by benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), ultraviolet (UV) light and the alkylating agent methyl methanesulfonate (MMS). As TLS polymerases are intrinsically error-prone, tight regulation of their activity is required. One level of control is provided by ubiquitination of the homotrimeric DNA clamp PCNA at lysine residue 164 (PCNA-Ub). We here show that Polκ can function independently of PCNA modification and that Polη can function as a backup during TLS of MMS-induced lesions. Compared to cell lines deficient for PCNA modification (PcnaK164R) or Polκ, double mutant cell lines display hypersensitivity to MMS but not to BPDE or UV-C. Double mutant cells also displayed delayed post-replicative TLS, accumulate higher levels of replication stress and delayed S-phase progression. Furthermore, we show that Polη and Polκ are redundant in the DNA damage bypass of MMS-induced DNA damage. Taken together, we provide evidence for PCNA-Ub-independent activation of Polκ and establish Polη as an important backup polymerase in the absence of Polκ in response to MMS-induced DNA damage. PMID:25505145

Identification of amino acid residues involved in the dRP-lyase activity of human Pol ι.

PubMed

Miropolskaya, Nataliya; Petushkov, Ivan; Kulbachinskiy, Andrey; Makarova, Alena V

2017-08-31

Besides X-family DNA polymerases (first of all, Pol β) several other human DNA polymerases from Y- and A- families were shown to possess the dRP-lyase activity and could serve as backup polymerases in base excision repair (Pol ι, Rev1, Pol γ and Pol θ). However the exact position of the active sites and the amino acid residues involved in the dRP-lyase activity in Y- and A- family DNA polymerases are not known. Here we carried out functional analysis of fifteen amino acid residues possibly involved in the dRP-lyase activity of human Pol ι. We show that substitutions of residues Q59, K60 and K207 impair the dRP-lyase activity of Pol ι while residues in the HhH motif of the thumb domain are dispensable for this activity. While both K60G and K207A substitutions decrease Schiff-base intermediate formation during dRP group cleavage, the latter substitution also strongly affects the DNA polymerase activity of Pol ι, suggesting that it may impair DNA binding. These data are consistent with an important role of the N-terminal region in the dRP-lyase activity of Pol ι, with possible involvement of residues from the finger domain in the dRP group cleavage.

Primer-Independent DNA Synthesis by a Family B DNA Polymerase from Self-Replicating Mobile Genetic Elements.

PubMed

Redrejo-Rodríguez, Modesto; Ordóñez, Carlos D; Berjón-Otero, Mónica; Moreno-González, Juan; Aparicio-Maldonado, Cristian; Forterre, Patrick; Salas, Margarita; Krupovic, Mart

2017-11-07

Family B DNA polymerases (PolBs) play a central role during replication of viral and cellular chromosomes. Here, we report the discovery of a third major group of PolBs, which we denote primer-independent PolB (piPolB), that might be a link between the previously known protein-primed and RNA/DNA-primed PolBs. PiPolBs are encoded by highly diverse mobile genetic elements, pipolins, integrated in the genomes of diverse bacteria and also present as circular plasmids in mitochondria. Biochemical characterization showed that piPolB displays efficient DNA polymerization activity that can use undamaged and damaged templates and is endowed with proofreading and strand displacement capacities. Remarkably, the protein is also capable of template-dependent de novo DNA synthesis, i.e., DNA-priming activity, thereby breaking the long-standing dogma that replicative DNA polymerases require a pre-existing primer for DNA synthesis. We suggest that piPolBs are involved in self-replication of pipolins and may also contribute to bacterial DNA damage tolerance. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Multi-Pixel Simultaneous Classification of PolSAR Image Using Convolutional Neural Networks

PubMed Central

Xu, Xin; Gui, Rong; Pu, Fangling

2018-01-01

Convolutional neural networks (CNN) have achieved great success in the optical image processing field. Because of the excellent performance of CNN, more and more methods based on CNN are applied to polarimetric synthetic aperture radar (PolSAR) image classification. Most CNN-based PolSAR image classification methods can only classify one pixel each time. Because all the pixels of a PolSAR image are classified independently, the inherent interrelation of different land covers is ignored. We use a fixed-feature-size CNN (FFS-CNN) to classify all pixels in a patch simultaneously. The proposed method has several advantages. First, FFS-CNN can classify all the pixels in a small patch simultaneously. When classifying a whole PolSAR image, it is faster than common CNNs. Second, FFS-CNN is trained to learn the interrelation of different land covers in a patch, so it can use the interrelation of land covers to improve the classification results. The experiments of FFS-CNN are evaluated on a Chinese Gaofen-3 PolSAR image and other two real PolSAR images. Experiment results show that FFS-CNN is comparable with the state-of-the-art PolSAR image classification methods. PMID:29510499

Multi-Pixel Simultaneous Classification of PolSAR Image Using Convolutional Neural Networks.

PubMed

Wang, Lei; Xu, Xin; Dong, Hao; Gui, Rong; Pu, Fangling

2018-03-03

Convolutional neural networks (CNN) have achieved great success in the optical image processing field. Because of the excellent performance of CNN, more and more methods based on CNN are applied to polarimetric synthetic aperture radar (PolSAR) image classification. Most CNN-based PolSAR image classification methods can only classify one pixel each time. Because all the pixels of a PolSAR image are classified independently, the inherent interrelation of different land covers is ignored. We use a fixed-feature-size CNN (FFS-CNN) to classify all pixels in a patch simultaneously. The proposed method has several advantages. First, FFS-CNN can classify all the pixels in a small patch simultaneously. When classifying a whole PolSAR image, it is faster than common CNNs. Second, FFS-CNN is trained to learn the interrelation of different land covers in a patch, so it can use the interrelation of land covers to improve the classification results. The experiments of FFS-CNN are evaluated on a Chinese Gaofen-3 PolSAR image and other two real PolSAR images. Experiment results show that FFS-CNN is comparable with the state-of-the-art PolSAR image classification methods.

Intelligente Messsysteme - Mehrwert für unterschiedliche Stufen der Wertschöpfung

NASA Astrophysics Data System (ADS)

Deppe, Benjamin

Die Veränderung der Energiewirtschaft schreitet kontinuierlich voran - und wird mit Gesetz zur Digitalisierung der Energiewende nicht abgeschlossen sein. Vielmehr steigen die Innovationsgeschwindigkeit und die Erwartungshaltung der Kunden. Dieses Kapitel beschreibt, wie intelligente Messsysteme die Basis für neue Möglichkeiten schaffen und wie sich diese Veränderungen auf die Wertschöpfung auswirken. Der Fokus liegt dabei auf dem Wandel der einzelnen Wertschöpfungsstufen im Verlauf der Liberalisierung des Messwesens und dem seit dem 02.09.2016 verbindlichen Messstellenbetriebsgesetzes. Der Beitrag zeigt auf, wie sich bisher getrennte Wertschöpfungsstufen nunmehr direkt berühren und miteinander interagieren. Deutlich wird dadurch, wie Informationen zu Mehrwert führen können - aber auch, welche Fragen noch zu beantworten sind und welche Hürden es zu überwinden gilt.

Explosive mutation accumulation triggered by heterozygous human Pol ε proofreading-deficiency is driven by suppression of mismatch repair

PubMed Central

Campbell, Brittany B; Ungerleider, Nathan; Light, Nicholas; Wu, Tong; LeCompte, Kimberly G; Goksenin, A Yasemin; Bunnell, Bruce A; Tabori, Uri; Shlien, Adam

2018-01-01

Tumors defective for DNA polymerase (Pol) ε proofreading have the highest tumor mutation burden identified. A major unanswered question is whether loss of Pol ε proofreading by itself is sufficient to drive this mutagenesis, or whether additional factors are necessary. To address this, we used a combination of next generation sequencing and in vitro biochemistry on human cell lines engineered to have defects in Pol ε proofreading and mismatch repair. Absent mismatch repair, monoallelic Pol ε proofreading deficiency caused a rapid increase in a unique mutation signature, similar to that observed in tumors from patients with biallelic mismatch repair deficiency and heterozygous Pol ε mutations. Restoring mismatch repair was sufficient to suppress the explosive mutation accumulation. These results strongly suggest that concomitant suppression of mismatch repair, a hallmark of colorectal and other aggressive cancers, is a critical force for driving the explosive mutagenesis seen in tumors expressing exonuclease-deficient Pol ε. PMID:29488881

Explosive mutation accumulation triggered by heterozygous human Pol ε proofreading-deficiency is driven by suppression of mismatch repair.

PubMed

Hodel, Karl P; de Borja, Richard; Henninger, Erin E; Campbell, Brittany B; Ungerleider, Nathan; Light, Nicholas; Wu, Tong; LeCompte, Kimberly G; Goksenin, A Yasemin; Bunnell, Bruce A; Tabori, Uri; Shlien, Adam; Pursell, Zachary F

2018-02-28

Tumors defective for DNA polymerase (Pol) ε proofreading have the highest tumor mutation burden identified. A major unanswered question is whether loss of Pol ε proofreading by itself is sufficient to drive this mutagenesis, or whether additional factors are necessary. To address this, we used a combination of next generation sequencing and in vitro biochemistry on human cell lines engineered to have defects in Pol ε proofreading and mismatch repair. Absent mismatch repair, monoallelic Pol ε proofreading deficiency caused a rapid increase in a unique mutation signature, similar to that observed in tumors from patients with biallelic mismatch repair deficiency and heterozygous Pol ε mutations. Restoring mismatch repair was sufficient to suppress the explosive mutation accumulation. These results strongly suggest that concomitant suppression of mismatch repair, a hallmark of colorectal and other aggressive cancers, is a critical force for driving the explosive mutagenesis seen in tumors expressing exonuclease-deficient Pol ε. © 2018, Hodel et al.

Mitochondrial DNA replication: a PrimPol perspective

PubMed Central

Bailey, Laura J.

2017-01-01

PrimPol, (primase–polymerase), the most recently identified eukaryotic polymerase, has roles in both nuclear and mitochondrial DNA maintenance. PrimPol is capable of acting as a DNA polymerase, with the ability to extend primers and also bypass a variety of oxidative and photolesions. In addition, PrimPol also functions as a primase, catalysing the preferential formation of DNA primers in a zinc finger-dependent manner. Although PrimPol's catalytic activities have been uncovered in vitro, we still know little about how and why it is targeted to the mitochondrion and what its key roles are in the maintenance of this multicopy DNA molecule. Unlike nuclear DNA, the mammalian mitochondrial genome is circular and the organelle has many unique proteins essential for its maintenance, presenting a differing environment within which PrimPol must function. Here, we discuss what is currently known about the mechanisms of DNA replication in the mitochondrion, the proteins that carry out these processes and how PrimPol is likely to be involved in assisting this vital cellular process. PMID:28408491

Role for the MED21-MED7 Hinge in Assembly of the Mediator-RNA Polymerase II Holoenzyme.

PubMed

Sato, Shigeo; Tomomori-Sato, Chieri; Tsai, Kuang-Lei; Yu, Xiaodi; Sardiu, Mihaela; Saraf, Anita; Washburn, Michael P; Florens, Laurence; Asturias, Francisco J; Conaway, Ronald C; Conaway, Joan W

2016-12-23

Mediator plays an integral role in activation of RNA polymerase II (Pol II) transcription. A key step in activation is binding of Mediator to Pol II to form the Mediator-Pol II holoenzyme. Here, we exploit a combination of biochemistry and macromolecular EM to investigate holoenzyme assembly. We identify a subset of human Mediator head module subunits that bind Pol II independent of other subunits and thus probably contribute to a major Pol II binding site. In addition, we show that binding of human Mediator to Pol II depends on the integrity of a conserved "hinge" in the middle module MED21-MED7 heterodimer. Point mutations in the hinge region leave core Mediator intact but lead to increased disorder of the middle module and markedly reduced affinity for Pol II. These findings highlight the importance of Mediator conformation for holoenzyme assembly. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Molecular basis for PrimPol recruitment to replication forks by RPA.

PubMed

Guilliam, Thomas A; Brissett, Nigel C; Ehlinger, Aaron; Keen, Benjamin A; Kolesar, Peter; Taylor, Elaine M; Bailey, Laura J; Lindsay, Howard D; Chazin, Walter J; Doherty, Aidan J

2017-05-23

DNA damage and secondary structures can stall the replication machinery. Cells possess numerous tolerance mechanisms to complete genome duplication in the presence of such impediments. In addition to translesion synthesis (TLS) polymerases, most eukaryotic cells contain a multifunctional replicative enzyme called primase-polymerase (PrimPol) that is capable of directly bypassing DNA damage by TLS, as well as repriming replication downstream of impediments. Here, we report that PrimPol is recruited to reprime through its interaction with RPA. Using biophysical and crystallographic approaches, we identify that PrimPol possesses two RPA-binding motifs and ascertained the key residues required for these interactions. We demonstrate that one of these motifs is critical for PrimPol's recruitment to stalled replication forks in vivo. In addition, biochemical analysis reveals that RPA serves to stimulate the primase activity of PrimPol. Together, these findings provide significant molecular insights into PrimPol's mode of recruitment to stalled forks to facilitate repriming and restart.