WorldWideScience

Sample records for robust expression driven

  1. Robust and regulatory expression of defensin A gene driven by vitellogenin promoter in transgenic Anopheles stephensi

    Institute of Scientific and Technical Information of China (English)

    CHEN XiaoGuang; ZHANG YaJing; ZHENG XueLi; WANG ChunMei

    2007-01-01

    The use of genetically modified mosquitoes to reduce or replace field populations is a new strategy to control mosquito-borne diseases. The precondition of the implementation of this strategy is the ability to manipulate the genome of mosquitoes and to induce specific expression of the effector molecules driven by a suitable promoter. The objective of this study is to evaluate the expression of defensin A gene of Anopheles sinensis under the control of a vitellogenin promoter in transgenic Anopheles stephensi. The regulatory region of Anopheles gambiae vitellogenin was cloned and subcloned into transfer vector pSLFa consisting of an expression cassette with defensin A coding sequence. Then, the expression cassette was transferred into transformation vector pBac[3xP3-DsRedafm] using Asc I digestion. The recombinant plasmid DNA of pBac[3xP3DsRed-AgVgT2-DefA] and helper plasmid DNA of phsp-pBac were micro-injected into embryos of An. stephensi. The positive transgenic mosquitoes were screened by observing specific red fluorescence in the eyes of G1 larvae. Southern blot analysis showed that a single-copy transgene integrated into the genome of An. stephensi. RT-PCR analysis showed that the defensin A gene expressed specifically in fat bodies of female mosquitoes after a blood meal. Interestingly, the mRNA of defensin A is more stable compared with that of the endogenous vitellogenin gene. After multiple blood meals, the expression of defensin A appeared as a reducible and non-cycling type, a crucial feature for its anti-pathogen effect. From data above, we concluded that the regulatory function of the Vg promoter and the expression of defensin A gene were relatively conserved in different species of anopheles mosquitoes. These molecules could be used as candidates in the development of genetically modified mosquitoes.

  2. Robust facial expression recognition via compressive sensing.

    Science.gov (United States)

    Zhang, Shiqing; Zhao, Xiaoming; Lei, Bicheng

    2012-01-01

    Recently, compressive sensing (CS) has attracted increasing attention in the areas of signal processing, computer vision and pattern recognition. In this paper, a new method based on the CS theory is presented for robust facial expression recognition. The CS theory is used to construct a sparse representation classifier (SRC). The effectiveness and robustness of the SRC method is investigated on clean and occluded facial expression images. Three typical facial features, i.e., the raw pixels, Gabor wavelets representation and local binary patterns (LBP), are extracted to evaluate the performance of the SRC method. Compared with the nearest neighbor (NN), linear support vector machines (SVM) and the nearest subspace (NS), experimental results on the popular Cohn-Kanade facial expression database demonstrate that the SRC method obtains better performance and stronger robustness to corruption and occlusion on robust facial expression recognition tasks.

  3. Noise Robust Speech Recognition Applied to Voice-Driven Wheelchair

    Science.gov (United States)

    Sasou, Akira; Kojima, Hiroaki

    2009-12-01

    Conventional voice-driven wheelchairs usually employ headset microphones that are capable of achieving sufficient recognition accuracy, even in the presence of surrounding noise. However, such interfaces require users to wear sensors such as a headset microphone, which can be an impediment, especially for the hand disabled. Conversely, it is also well known that the speech recognition accuracy drastically degrades when the microphone is placed far from the user. In this paper, we develop a noise robust speech recognition system for a voice-driven wheelchair. This system can achieve almost the same recognition accuracy as the headset microphone without wearing sensors. We verified the effectiveness of our system in experiments in different environments, and confirmed that our system can achieve almost the same recognition accuracy as the headset microphone without wearing sensors.

  4. Robust control of a hydraulically driven flexible arm

    Institute of Scientific and Technical Information of China (English)

    Guang LI; Khajepour AMIR

    2004-01-01

    A new robust controller is proposed to regulate both flexural vibrations and rigid body motion of a hydraulically driven flexible arm. The controller combines backstepping control and sliding mode to arrive at a controller capable of dealing with a nonlinear system with uncertainties. The sliding mode technique is used to achieve an asymptotic joint angle and vibration regulation in the presence of payload uncertainty by providing a virtual torque input at the joint while the backstepping technique is used to regulate the spool position of a hydraulic valve to provide the required torque. It is shown that there is no chatter in the hydraulic valve, which results in smoother operation of the system.

  5. Robust Real-Time Musculoskeletal Modeling driven by Electromyograms.

    Science.gov (United States)

    Durandau, Guillaume; Farina, Dario; Sartori, Massimo

    2017-05-12

    Current clinical biomechanics involves lengthy data acquisition and time-consuming offline analyses and current biomechanical models cannot be used for real-time control in man-machine interfaces. We developed a method that enables online analysis of neuromusculoskeletal function in vivo in the intact human. We used electromyography (EMG)-driven musculoskeletal modeling to simulate all transformations from muscle excitation onset (EMGs) to mechanical moment production around multiple lower-limb degrees of freedom (DOFs). We developed a calibration algorithm that enables adjusting musculoskeletal model parameters specifically to an individual's anthropometry and force-generating capacity. We incorporated the modeling paradigm into a computationally efficient, generic framework that can be interfaced in real-time with any movement data collection system. The framework demonstrated the ability of computing forces in 13 lower-limb muscle-tendon units and resulting moments about three joint DOFs simultaneously in real-time. Remarkably, it was capable of extrapolating beyond calibration conditions, i.e. predicting accurate joint moments during six unseen tasks and one unseen DOF. The proposed framework can dramatically reduce evaluation latency in current clinical biomechanics and open up new avenues for establishing prompt and personalized treatments, as well as for establishing natural interfaces between patients and rehabilitation systems. The integration of EMG with numerical modeling will enable simulating realistic neuromuscular strategies in conditions including muscular/orthopedic deficit, which could not be robustly simulated via pure modeling formulations. This will enable translation to clinical settings and development of healthcare technologies including real-time bio-feedback of internal mechanical forces and direct patient-machine interfacing.

  6. Robustness of norm-driven cooperation in the commons.

    Science.gov (United States)

    Schlüter, Maja; Tavoni, Alessandro; Levin, Simon

    2016-01-13

    Sustainable use of common-pool resources such as fish, water or forests depends on the cooperation of resource users that restrain their individual extraction to socially optimal levels. Empirical evidence has shown that under certain social and biophysical conditions, self-organized cooperation in the commons can evolve. Global change, however, may drastically alter these conditions. We assess the robustness of cooperation to environmental variability in a stylized model of a community that harvests a shared resource. Community members follow a norm of socially optimal resource extraction, which is enforced through social sanctioning. Our results indicate that both resource abundance and a small increase in resource variability can lead to collapse of cooperation observed in the no-variability case, while either scarcity or large variability have the potential to stabilize it. The combined effects of changes in amount and variability can reinforce or counteract each other depending on their size and the initial level of cooperation in the community. If two socially separate groups are ecologically connected through resource leakage, cooperation in one can destabilize the other. These findings provide insights into possible effects of global change and spatial connectivity, indicating that there is no simple answer as to their effects on cooperation and sustainable resource use. © 2016 The Author(s).

  7. A robust data-driven approach for gene ontology annotation.

    Science.gov (United States)

    Li, Yanpeng; Yu, Hong

    2014-01-01

    Gene ontology (GO) and GO annotation are important resources for biological information management and knowledge discovery, but the speed of manual annotation became a major bottleneck of database curation. BioCreative IV GO annotation task aims to evaluate the performance of system that automatically assigns GO terms to genes based on the narrative sentences in biomedical literature. This article presents our work in this task as well as the experimental results after the competition. For the evidence sentence extraction subtask, we built a binary classifier to identify evidence sentences using reference distance estimator (RDE), a recently proposed semi-supervised learning method that learns new features from around 10 million unlabeled sentences, achieving an F1 of 19.3% in exact match and 32.5% in relaxed match. In the post-submission experiment, we obtained 22.1% and 35.7% F1 performance by incorporating bigram features in RDE learning. In both development and test sets, RDE-based method achieved over 20% relative improvement on F1 and AUC performance against classical supervised learning methods, e.g. support vector machine and logistic regression. For the GO term prediction subtask, we developed an information retrieval-based method to retrieve the GO term most relevant to each evidence sentence using a ranking function that combined cosine similarity and the frequency of GO terms in documents, and a filtering method based on high-level GO classes. The best performance of our submitted runs was 7.8% F1 and 22.2% hierarchy F1. We found that the incorporation of frequency information and hierarchy filtering substantially improved the performance. In the post-submission evaluation, we obtained a 10.6% F1 using a simpler setting. Overall, the experimental analysis showed our approaches were robust in both the two tasks.

  8. Robust control of a class of chaotic and hyperchaotic driven systems

    Science.gov (United States)

    Mkaouar, Hanéne; Boubaker, Olfa

    2017-01-01

    This paper proposes new conditions which are sufficient for robust control of a class of chaotic and hyperchaotic driven systems. The drive-driven systems are characterized by non-identical uncertain complex dynamics where complexities are mainly introduced by the switching nature of their vector fields. The controller design is achieved using linear matrix inequalities (LMIs) and the so-called S-procedure and then validated using two numerical examples. To illustrate the robustness of the proposed approach, a comparative study is also established with regard to a related approach.

  9. Robust control of a class of chaotic and hyperchaotic driven systems

    Indian Academy of Sciences (India)

    HANÉNE MKAOUAR; OLFA BOUBAKER

    2017-01-01

    This paper proposes new conditions which are sufficient for robust control of a class of chaotic and hyperchaotic driven systems. The drive–driven systems are characterized by non-identical uncertain complex dynamics where complexities are mainly introduced by the switching nature of their vector fields. The controllerdesign is achieved using linear matrix inequalities (LMIs) and the so-called S-procedure and then validated using two numerical examples. To illustrate the robustness of the proposed approach, a comparative study is also established with regard to a related approach.

  10. Goal-Driven Autonomy and Robust Architecture for Long-Duration Missions (Year 1: 1 July 2013 - 31 July 2014)

    Science.gov (United States)

    2014-09-30

    1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Goal-Driven Autonomy and Robust Architecture for Long...robust long-duration agent autonomy and to provide a prototype implementation that exhibits flexible, goal-driven autonomy on an actual physical...DATES COVERED 00-00-2014 to 00-00-2014 4. TITLE AND SUBTITLE Goal-Driven Autonomy and Robust Architecture for Long-Duration Missions (Year 1: 1

  11. Data-driven quantification of the robustness and sensitivity of cell signaling networks

    Science.gov (United States)

    Mukherjee, Sayak; Seok, Sang-Cheol; Vieland, Veronica J.; Das, Jayajit

    2013-12-01

    Robustness and sensitivity of responses generated by cell signaling networks has been associated with survival and evolvability of organisms. However, existing methods analyzing robustness and sensitivity of signaling networks ignore the experimentally observed cell-to-cell variations of protein abundances and cell functions or contain ad hoc assumptions. We propose and apply a data-driven maximum entropy based method to quantify robustness and sensitivity of Escherichia coli (E. coli) chemotaxis signaling network. Our analysis correctly rank orders different models of E. coli chemotaxis based on their robustness and suggests that parameters regulating cell signaling are evolutionary selected to vary in individual cells according to their abilities to perturb cell functions. Furthermore, predictions from our approach regarding distribution of protein abundances and properties of chemotactic responses in individual cells based on cell population averaged data are in excellent agreement with their experimental counterparts. Our approach is general and can be used to evaluate robustness as well as generate predictions of single cell properties based on population averaged experimental data in a wide range of cell signaling systems.

  12. Robust tracking control for a class of electrically driven flexible-joint robots without velocity measurements

    Science.gov (United States)

    Chang, Yeong-Chan; Yen, Hui-Min

    2012-02-01

    This article addresses the motion tracking control for a class of flexible-joint robotic manipulators actuated by brushed direct current motors. This class of electrically driven flexible-joint robots is perturbed by time-varying parametric uncertainties and external disturbances. A novel observer-based robust dynamic feedback tracking controller without velocity measurements will be developed such that the resulting closed-loop system is locally stable, all the states and signals are bounded and the trajectory tracking errors can be made as small as possible. Only the measurements of link position and armature current are required for feedback and so the number of sensors in the practical implementation of the developed control scheme can be greatly reduced. The observer structure is of reduced order in the sense that the observer is constructed only to estimate the velocity signals and whose dimension is half of the dimension of flexible-joint robots. Especially, for the set-point regulation problem, the developed controller is simplified to a linear time-invariant controller. Consequently, the robust tracking control scheme developed in this study can be extended to handle a broader class of uncertain electrically driven flexible-joint robots and the developed robust control schemes possess the properties of computational simplicity and easy implementation. Finally, simulation results are presented to demonstrate the effectiveness of the proposed control algorithms.

  13. Robust, synergistic regulation of human gene expression using TALE activators.

    Science.gov (United States)

    Maeder, Morgan L; Linder, Samantha J; Reyon, Deepak; Angstman, James F; Fu, Yanfang; Sander, Jeffry D; Joung, J Keith

    2013-03-01

    Artificial activators designed using transcription activator-like effector (TALE) technology have broad utility, but previous studies suggest that these monomeric proteins often exhibit low activities. Here we demonstrate that TALE activators can robustly function individually or in synergistic combinations to increase expression of endogenous human genes over wide dynamic ranges. These findings will encourage applications of TALE activators for research and therapy, and guide design of monomeric TALE-based fusion proteins.

  14. Data-Driven Temporal Filtering on Teager Energy Time Trajectory for Robust Speech Recognition

    Institute of Scientific and Technical Information of China (English)

    ZHAO Jun-hui; XIE Xiang; KUANG Jing-ming

    2006-01-01

    Data-driven temporal filtering technique is integrated into the time trajectory of Teager energy operation (TEO) based feature parameter for improving the robustness of speech recognition system against noise.Three kinds of data-driven temporal filters are investigated for the motivation of alleviating the harmful effects that the environmental factors have on the speech. The filters include: principle component analysis (PCA) based filters, linear discriminant analysis (LDA) based filters and minimum classification error (MCE) based filters. Detailed comparative analysis among these temporal filtering approaches applied in Teager energy domain is presented. It is shown that while all of them can improve the recognition performance of the original TEO based feature parameter in adverse environment, MCE based temporal filtering can provide the lowest error rate as SNR decreases than any other algorithms.

  15. Data-Driven Neural Network Model for Robust Reconstruction of Automobile Casting

    Science.gov (United States)

    Lin, Jinhua; Wang, Yanjie; Li, Xin; Wang, Lu

    2017-09-01

    In computer vision system, it is a challenging task to robustly reconstruct complex 3D geometries of automobile castings. However, 3D scanning data is usually interfered by noises, the scanning resolution is low, these effects normally lead to incomplete matching and drift phenomenon. In order to solve these problems, a data-driven local geometric learning model is proposed to achieve robust reconstruction of automobile casting. In order to relieve the interference of sensor noise and to be compatible with incomplete scanning data, a 3D convolution neural network is established to match the local geometric features of automobile casting. The proposed neural network combines the geometric feature representation with the correlation metric function to robustly match the local correspondence. We use the truncated distance field(TDF) around the key point to represent the 3D surface of casting geometry, so that the model can be directly embedded into the 3D space to learn the geometric feature representation; Finally, the training labels is automatically generated for depth learning based on the existing RGB-D reconstruction algorithm, which accesses to the same global key matching descriptor. The experimental results show that the matching accuracy of our network is 92.2% for automobile castings, the closed loop rate is about 74.0% when the matching tolerance threshold τ is 0.2. The matching descriptors performed well and retained 81.6% matching accuracy at 95% closed loop. For the sparse geometric castings with initial matching failure, the 3D matching object can be reconstructed robustly by training the key descriptors. Our method performs 3D reconstruction robustly for complex automobile castings.

  16. Robustness of learning that is based on covariance-driven synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Yonatan Loewenstein

    2008-03-01

    Full Text Available It is widely believed that learning is due, at least in part, to long-lasting modifications of the strengths of synapses in the brain. Theoretical studies have shown that a family of synaptic plasticity rules, in which synaptic changes are driven by covariance, is particularly useful for many forms of learning, including associative memory, gradient estimation, and operant conditioning. Covariance-based plasticity is inherently sensitive. Even a slight mistuning of the parameters of a covariance-based plasticity rule is likely to result in substantial changes in synaptic efficacies. Therefore, the biological relevance of covariance-based plasticity models is questionable. Here, we study the effects of mistuning parameters of the plasticity rule in a decision making model in which synaptic plasticity is driven by the covariance of reward and neural activity. An exact covariance plasticity rule yields Herrnstein's matching law. We show that although the effect of slight mistuning of the plasticity rule on the synaptic efficacies is large, the behavioral effect is small. Thus, matching behavior is robust to mistuning of the parameters of the covariance-based plasticity rule. Furthermore, the mistuned covariance rule results in undermatching, which is consistent with experimentally observed behavior. These results substantiate the hypothesis that approximate covariance-based synaptic plasticity underlies operant conditioning. However, we show that the mistuning of the mean subtraction makes behavior sensitive to the mistuning of the properties of the decision making network. Thus, there is a tradeoff between the robustness of matching behavior to changes in the plasticity rule and its robustness to changes in the properties of the decision making network.

  17. H∞ Robust Controller Design for an Induction Generator Driven by a Variable-Speed Wind Turbine

    Directory of Open Access Journals (Sweden)

    Seyed Mohammad Hoseini

    2011-01-01

    Full Text Available This paper presents the modeling and robust controller design design for a wind-driven induction generator system. a  robust controller for the static synchronous compensator (STATCOM and the variable blade pitch in a wind energy conversion system (WECS is designed to be controlled voltage and mechanical power. This controller leading to satisfactory damping characteristics achieved for the closed loop system. Effects of various system disturbances on the dynamic performance have been simulated, and the results comparison with output feedback controller reveal that the proposed controller is effective in regulating the load voltage and stabilizing the generator rotating speed for WECS. The nonlinear simulation was conducted and that comparison with the above linear simulation shows that the simulations carried out for small changes in system inputs is sufficiently accurate. For review performance against large disturbances from a symmetrical three-phase short circuit at infinity bus bar has been used  and the results show robust controller design as well as fluctuations resulting from the short circuit is damped.

  18. Pressure observer based adaptive robust trajectory tracking control of a parallel manipulator driven by pneumatic muscles

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This paper presents a pressure observer based adaptive robust controller (POARC) for posture trajectory tracking of a parallel manipulator driven by three pneumatic muscles without pressure sensors. Due to model errors of the static forces and friction forces of pneumatic muscles, simplified average flow rate characteristics of valves, unknown disturbances of entire system,and unmeasured pressures, there exist rather severe parametric uncertainties, nonlinear uncertainties and dynamic uncertainties in modeling of the parallel manipulator. A nonlinear pressure observer is constructed to estimate unknown pressures on the basis of a single-input-single-output (SISO) decoupling model that is simplified from the actual multiple-input-multiple-output (MIMO)coupling model of the parallel manipulator. Then, an adaptive robust controller integrated with the pressure observer is developed to accomplish high precision posture trajectory tracking of the parallel manipulator. The experimental results indicate that the system with the proposed POARC not only achieves good control accuracy and smooth movement but also maintains robustness to disturbances.

  19. Robustness

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Rizzuto, Enrico; Narasimhan, Harikrishna

    2012-01-01

    More frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure combined with increased requirements to efficiency in design and execution followed by increased risk of human errors has made the need of requirements to robustness of structures......, a theoretical and risk-based framework is presented which facilitates the quantification of robustness, and thus supports the formulation of pre-normative guidelines....

  20. Robust synchronization of an arbitrary number of spin-torque-driven vortex nano-oscillators

    Science.gov (United States)

    Erokhin, Sergey; Berkov, Dmitry

    2014-04-01

    Nonlinear magnetization dynamics in ferromagnetic nanoelements excited by a spin-polarized dc current is one of the most intensively studied phenomena in solid-state magnetism. Despite immense efforts, synchronization of oscillations induced in several such nanoelements [spin-torque-driven nano-oscillators (STNO)] still represents a major challenge from both the fundamental and technological points of view. In this paper we propose a system where synchronization of any number of STNOs, represented by magnetization vortices inside squared nanoelements, can be easily achieved. Using full-scale micromagnetic simulations we show that synchronization of these STNOs is extremely dynamically stable due to their very large coupling energy provided by the magnetodipolar interaction. Finally, we demonstrate that our concept allows robust synchronization of an arbitrary number of STNOs (arranged either as a one-dimensional chain or as a two-dimensional array), even when current supplying nanocontacts have a broad size distribution.

  1. Coordination, Organisation and Model-driven Approaches for Dynamic, Flexible, Robust Software and Services Engineering

    Science.gov (United States)

    Nieves, Juan Carlos; Padget, Julian; Vasconcelos, Wamberto; Staikopoulos, Athanasios; Cliffe, Owen; Dignum, Frank; Vázquez-Salceda, Javier; Clarke, Siobhán; Reed, Chris

    Enterprise systems are increasingly composed of (and even functioning as) components in a dynamic, digital ecosystem. On the one hand, this new situation requires flexible, spontaneous and opportunistic collaboration activities to be identified and established among (electronic) business parties. On the other, it demands engineering methods that are able to integrate new functionalities and behaviours into running systems composed by active, distributed, interdependent processes. Here we present a multi-level architecture that combines organisational and coordination theories with model driven development, for the implementation, deployment and management of dynamic, flexible and robust service-oriented business applications, combined with a service layer that accommodates semantic service description, fine-grained semantic service discovery and the dynamic adaptation of services to meet changing circumstances.

  2. Backaction-driven, robust, steady-state long-distance qubit entanglement over lossy channels

    Science.gov (United States)

    Motzoi, Felix; Halperin, Eli; Wang, Xiaoting; Whaley, K. Birgitta; Schirmer, Sophie

    2016-09-01

    We present a scheme for generating robust and persistent entanglement between qubits that do not interact and that are separated by a long and lossy transmission channel, using Markovian reservoir engineering. The proposal uses only the correlated decay into the common channel of remotely separated, driven single-photon qubit transitions. This simple scheme is generic and applicable to various experimental implementations, including circuit and cavity QED, with little experimental overhead compared with methods requiring dynamic control, initialization, measurement, or feedback. In addition to avoiding these inefficiencies, the simple protocol is highly robust against noise, miscalibration, and loss in the channel. We find high-quality solutions over a wide range of parameters and show that the optimal strategy reflects a transition from ballistic to diffusive photon transmission, going from symmetrically and coherently driving a common steady state to asymmetrically absorbing photons that are emitted from one qubit by the second. Detailed analysis of the role of the transmission channel shows that allowing bidirectional decay drastically increases indistinguishability and thereby quadratically suppresses infidelity.

  3. A 3D interactive multi-object segmentation tool using local robust statistics driven active contours.

    Science.gov (United States)

    Gao, Yi; Kikinis, Ron; Bouix, Sylvain; Shenton, Martha; Tannenbaum, Allen

    2012-08-01

    Extracting anatomical and functional significant structures renders one of the important tasks for both the theoretical study of the medical image analysis, and the clinical and practical community. In the past, much work has been dedicated only to the algorithmic development. Nevertheless, for clinical end users, a well designed algorithm with an interactive software is necessary for an algorithm to be utilized in their daily work. Furthermore, the software would better be open sourced in order to be used and validated by not only the authors but also the entire community. Therefore, the contribution of the present work is twofolds: first, we propose a new robust statistics based conformal metric and the conformal area driven multiple active contour framework, to simultaneously extract multiple targets from MR and CT medical imagery in 3D. Second, an open source graphically interactive 3D segmentation tool based on the aforementioned contour evolution is implemented and is publicly available for end users on multiple platforms. In using this software for the segmentation task, the process is initiated by the user drawn strokes (seeds) in the target region in the image. Then, the local robust statistics are used to describe the object features, and such features are learned adaptively from the seeds under a non-parametric estimation scheme. Subsequently, several active contours evolve simultaneously with their interactions being motivated by the principles of action and reaction-this not only guarantees mutual exclusiveness among the contours, but also no longer relies upon the assumption that the multiple objects fill the entire image domain, which was tacitly or explicitly assumed in many previous works. In doing so, the contours interact and converge to equilibrium at the desired positions of the desired multiple objects. Furthermore, with the aim of not only validating the algorithm and the software, but also demonstrating how the tool is to be used, we provide

  4. Adaptive robust trajectory tracking control of a parallel manipulator driven by pneumatic cylinders

    Directory of Open Access Journals (Sweden)

    Ce Shang

    2016-04-01

    Full Text Available Due to the compressibility of air, non-linear characteristics, and parameter uncertainties of pneumatic elements, the position control of a pneumatic cylinder or parallel platform is still very difficult while comparing with the systems driven by electric or hydraulic power. In this article, based on the basic dynamic model and descriptions of thermal processes, a controller integrated with online parameter estimation is proposed to improve the performance of a pneumatic cylinder controlled by a proportional valve. The trajectory tracking error is significantly decreased by applying this method. Moreover, the algorithm is expanded to the problem of posture trajectory tracking for the three-revolute prismatic spherical pneumatic parallel manipulator. Lyapunov’s method is used to give the proof of stability of the controller. Using NI-CompactRio, NI-PXI, and Veristand platform as the realistic controller hardware and data interactive environment, the adaptive robust control algorithm is applied to the physical system successfully. Experimental results and data analysis showed that the posture error of the platform could be about 0.5%–0.7% of the desired trajectory amplitude. By integrating this method to the mechatronic system, the pneumatic servo solutions can be much more competitive in the industrial market of position and posture control.

  5. Robust optimal control of material flows in demand-driven supply networks

    Science.gov (United States)

    Laumanns, Marco; Lefeber, Erjen

    2006-04-01

    We develop a model based on stochastic discrete-time controlled dynamical systems in order to derive optimal policies for controlling the material flow in supply networks. Each node in the network is described as a transducer such that the dynamics of the material and information flows within the entire network can be expressed by a system of first-order difference equations, where some inputs to the system act as external disturbances. We apply methods from constrained robust optimal control to compute the explicit control law as a function of the current state. For the numerical examples considered, these control laws correspond to certain classes of optimal ordering policies from inventory management while avoiding, however, any a priori assumptions about the general form of the policy.

  6. Evolution of robustness to noise and mutation in gene expression dynamics.

    Directory of Open Access Journals (Sweden)

    Kunihiko Kaneko

    Full Text Available Phenotype of biological systems needs to be robust against mutation in order to sustain themselves between generations. On the other hand, phenotype of an individual also needs to be robust against fluctuations of both internal and external origins that are encountered during growth and development. Is there a relationship between these two types of robustness, one during a single generation and the other during evolution? Could stochasticity in gene expression have any relevance to the evolution of these types of robustness? Robustness can be defined by the sharpness of the distribution of phenotype; the variance of phenotype distribution due to genetic variation gives a measure of 'genetic robustness', while that of isogenic individuals gives a measure of 'developmental robustness'. Through simulations of a simple stochastic gene expression network that undergoes mutation and selection, we show that in order for the network to acquire both types of robustness, the phenotypic variance induced by mutations must be smaller than that observed in an isogenic population. As the latter originates from noise in gene expression, this signifies that the genetic robustness evolves only when the noise strength in gene expression is larger than some threshold. In such a case, the two variances decrease throughout the evolutionary time course, indicating increase in robustness. The results reveal how noise that cells encounter during growth and development shapes networks' robustness to stochasticity in gene expression, which in turn shapes networks' robustness to mutation. The necessary condition for evolution of robustness, as well as the relationship between genetic and developmental robustness, is derived quantitatively through the variance of phenotypic fluctuations, which are directly measurable experimentally.

  7. Evolution of robustness to noise and mutation in gene expression dynamics.

    Science.gov (United States)

    Kaneko, Kunihiko

    2007-05-09

    Phenotype of biological systems needs to be robust against mutation in order to sustain themselves between generations. On the other hand, phenotype of an individual also needs to be robust against fluctuations of both internal and external origins that are encountered during growth and development. Is there a relationship between these two types of robustness, one during a single generation and the other during evolution? Could stochasticity in gene expression have any relevance to the evolution of these types of robustness? Robustness can be defined by the sharpness of the distribution of phenotype; the variance of phenotype distribution due to genetic variation gives a measure of 'genetic robustness', while that of isogenic individuals gives a measure of 'developmental robustness'. Through simulations of a simple stochastic gene expression network that undergoes mutation and selection, we show that in order for the network to acquire both types of robustness, the phenotypic variance induced by mutations must be smaller than that observed in an isogenic population. As the latter originates from noise in gene expression, this signifies that the genetic robustness evolves only when the noise strength in gene expression is larger than some threshold. In such a case, the two variances decrease throughout the evolutionary time course, indicating increase in robustness. The results reveal how noise that cells encounter during growth and development shapes networks' robustness to stochasticity in gene expression, which in turn shapes networks' robustness to mutation. The necessary condition for evolution of robustness, as well as the relationship between genetic and developmental robustness, is derived quantitatively through the variance of phenotypic fluctuations, which are directly measurable experimentally.

  8. Robust global microRNA expression profiling using next-generation sequencing technologies.

    Science.gov (United States)

    Tam, Shirley; de Borja, Richard; Tsao, Ming-Sound; McPherson, John D

    2014-03-01

    miRNAs are a class of regulatory molecules involved in a wide range of cellular functions, including growth, development and apoptosis. Given their widespread roles in biological processes, understanding their patterns of expression in normal and diseased states will provide insights into the consequences of aberrant expression. As such, global miRNA expression profiling of human malignancies is gaining popularity in both basic and clinically driven research. However, to date, the majority of such analyses have used microarrays and quantitative real-time PCR. With the introduction of digital count technologies, such as next-generation sequencing (NGS) and the NanoString nCounter System, we have at our disposal many more options. To make effective use of these different platforms, the strengths and pitfalls of several miRNA profiling technologies were assessed, including a microarray platform, NGS technologies and the NanoString nCounter System. Overall, NGS had the greatest detection sensitivity, largest dynamic range of detection and highest accuracy in differential expression analysis when compared with gold-standard quantitative real-time PCR. Its technical reproducibility was high, with intrasample correlations of at least 0.95 in all cases. Furthermore, miRNA analysis of formalin-fixed, paraffin-embedded (FFPE) tissue was also evaluated. Expression profiles between paired frozen and FFPE samples were similar, with Spearman's ρ>0.93. These results show the superior sensitivity, accuracy and robustness of NGS for the comprehensive profiling of miRNAs in both frozen and FFPE tissues.

  9. Data-Driven Guides: Supporting Expressive Design for Information Graphics.

    Science.gov (United States)

    Kim, Nam Wook; Schweickart, Eston; Liu, Zhicheng; Dontcheva, Mira; Li, Wilmot; Popovic, Jovan; Pfister, Hanspeter

    2017-01-01

    In recent years, there is a growing need for communicating complex data in an accessible graphical form. Existing visualization creation tools support automatic visual encoding, but lack flexibility for creating custom design; on the other hand, freeform illustration tools require manual visual encoding, making the design process time-consuming and error-prone. In this paper, we present Data-Driven Guides (DDG), a technique for designing expressive information graphics in a graphic design environment. Instead of being confined by predefined templates or marks, designers can generate guides from data and use the guides to draw, place and measure custom shapes. We provide guides to encode data using three fundamental visual encoding channels: length, area, and position. Users can combine more than one guide to construct complex visual structures and map these structures to data. When underlying data is changed, we use a deformation technique to transform custom shapes using the guides as the backbone of the shapes. Our evaluation shows that data-driven guides allow users to create expressive and more accurate custom data-driven graphics.

  10. Robust control of wire-driven system using linear DC motor; Linear DC motor ni yoru wire kudokei no robust seigyo

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, M. [Asahi Chemical Industry Co. Ltd., Tokyo (Japan); Hashimoto, H. [The University of Tokyo, Tokyo (Japan). Institute of Industrial Science

    1994-10-20

    The driving system and its control method were studied to miniaturizing the robot and multiplying its degree of freedom. Through designing the composition of force-transferring device driven by wire and actuator done by thin linear motor, the space can be saved by separating the places needing the force-transferring device and those doing the actuator. However, the driving by wire has the unknown stiffness, backlash, friction and other hardly controllable elements. Three types of robust control, observer-based control, sliding-mode control and H{infinity} control were applied and mutually compared. The H{infinity} control was a H{infinity} norm which was adopted, with optimization, into the evaluation function to measure the objective transfer function. Enabling the comparatively easy designing of high-gain controller to comply with the objective, the H{infinity} control theory was known to be effectively applicable even to the objective having the backlash, friction and resonance point. The present control was robust also against the fluctuation in load. 10 refs., 15 figs., 2 tabs.

  11. Science Letters: A robust statistical procedure to discover expression biomarkers using microarray genomic expression data

    Institute of Scientific and Technical Information of China (English)

    ZOU Yang-yun; YANG Jian; ZHU Jun

    2006-01-01

    Microarray has become increasingly popular biotechnology in biological and medical researches, and has been widely applied in classification of treatment subtypes using expression patterns of biomarkers. We developed a statistical procedure to identify expression biomarkers for treatment subtype classification by constructing an F-statistic based on Henderson method Ⅲ.Monte Carlo simulations were conducted to examine the robustness and efficiency of the proposed method. Simulation results showed that our method could provide satisfying power of identifying differentially expressed genes (DEGs) with false discovery rate (FDR) lower than the given type Ⅰ error rate. In addition, we analyzed a leukemia dataset collected from 38 leukemia patients with 27 samples diagnosed as acute lymphoblastic leukemia (ALL) and 11 samples as acute myeloid leukemia (AML). We compared our results with those from the methods of significance analysis of microarray (SAM) and microarray analysis of variance (MAANOVA). Among these three methods, only expression biomarkers identified by our method can precisely identify the three human acute leukemia subtypes.

  12. Robust Data-Driven Inference for Density-Weighted Average Derivatives

    DEFF Research Database (Denmark)

    Cattaneo, Matias D.; Crump, Richard K.; Jansson, Michael

    This paper presents a new data-driven bandwidth selector compatible with the small bandwidth asymptotics developed in Cattaneo, Crump, and Jansson (2009) for density- weighted average derivatives. The new bandwidth selector is of the plug-in variety, and is obtained based on a mean squared error...

  13. Robust expression of a bioactive mammalian protein in Chlamydomonas chloroplast

    Energy Technology Data Exchange (ETDEWEB)

    Mayfield, Stephen P

    2015-01-13

    Methods and compositions are disclosed to engineer chloroplast comprising heterologous mammalian genes via a direct replacement of chloroplast Photosystem II (PSII) reaction center protein coding regions to achieve expression of recombinant protein above 5% of total protein. When algae is used, algal expressed protein is produced predominantly as a soluble protein where the functional activity of the peptide is intact. As the host algae is edible, production of biologics in this organism for oral delivery of proteins/peptides, especially gut active proteins, without purification is disclosed.

  14. Data-driven robust approximate optimal tracking control for unknown general nonlinear systems using adaptive dynamic programming method.

    Science.gov (United States)

    Zhang, Huaguang; Cui, Lili; Zhang, Xin; Luo, Yanhong

    2011-12-01

    In this paper, a novel data-driven robust approximate optimal tracking control scheme is proposed for unknown general nonlinear systems by using the adaptive dynamic programming (ADP) method. In the design of the controller, only available input-output data is required instead of known system dynamics. A data-driven model is established by a recurrent neural network (NN) to reconstruct the unknown system dynamics using available input-output data. By adding a novel adjustable term related to the modeling error, the resultant modeling error is first guaranteed to converge to zero. Then, based on the obtained data-driven model, the ADP method is utilized to design the approximate optimal tracking controller, which consists of the steady-state controller and the optimal feedback controller. Further, a robustifying term is developed to compensate for the NN approximation errors introduced by implementing the ADP method. Based on Lyapunov approach, stability analysis of the closed-loop system is performed to show that the proposed controller guarantees the system state asymptotically tracking the desired trajectory. Additionally, the obtained control input is proven to be close to the optimal control input within a small bound. Finally, two numerical examples are used to demonstrate the effectiveness of the proposed control scheme.

  15. Subject independent facial expression recognition with robust face detection using a convolutional neural network.

    Science.gov (United States)

    Matsugu, Masakazu; Mori, Katsuhiko; Mitari, Yusuke; Kaneda, Yuji

    2003-01-01

    Reliable detection of ordinary facial expressions (e.g. smile) despite the variability among individuals as well as face appearance is an important step toward the realization of perceptual user interface with autonomous perception of persons. We describe a rule-based algorithm for robust facial expression recognition combined with robust face detection using a convolutional neural network. In this study, we address the problem of subject independence as well as translation, rotation, and scale invariance in the recognition of facial expression. The result shows reliable detection of smiles with recognition rate of 97.6% for 5600 still images of more than 10 subjects. The proposed algorithm demonstrated the ability to discriminate smiling from talking based on the saliency score obtained from voting visual cues. To the best of our knowledge, it is the first facial expression recognition model with the property of subject independence combined with robustness to variability in facial appearance.

  16. Robustness under functional constraint: the genetic network for temporal expression in Drosophila neurogenesis.

    Directory of Open Access Journals (Sweden)

    Akihiko Nakajima

    2010-04-01

    Full Text Available Precise temporal coordination of gene expression is crucial for many developmental processes. One central question in developmental biology is how such coordinated expression patterns are robustly controlled. During embryonic development of the Drosophila central nervous system, neural stem cells called neuroblasts express a group of genes in a definite order, which leads to the diversity of cell types. We produced all possible regulatory networks of these genes and examined their expression dynamics numerically. From the analysis, we identified requisite regulations and predicted an unknown factor to reproduce known expression profiles caused by loss-of-function or overexpression of the genes in vivo, as well as in the wild type. Following this, we evaluated the stability of the actual Drosophila network for sequential expression. This network shows the highest robustness against parameter variations and gene expression fluctuations among the possible networks that reproduce the expression profiles. We propose a regulatory module composed of three types of regulations that is responsible for precise sequential expression. This study suggests that the Drosophila network for sequential expression has evolved to generate the robust temporal expression for neuronal specification.

  17. Robust Neural Network Control of Electrically Driven Robot Manipulator using Backstepping Approach

    Directory of Open Access Journals (Sweden)

    Seyed Ehsan Shafiei

    2010-02-01

    Full Text Available A novel approach to neural network based tracking-control of robot manipulator including actuator dynamics is proposed by using of backstepping method. A simple two-step backstepping is considered for an nlink robotic system, and a feedforward neural controller is designed at second step where structured and unstructured uncertainties in robot dynamics and actuator model are approximated by this neural controller. Bounds of network reconstruction error and other imprecisions are estimated adaptively and for compensating them, a robust control signal is added and modified. Stability analysis is performed by the Lyapunov direct method and performance efficiency of the proposed controller is justified by the simulations.

  18. Proportionality between variances in gene expression induced by noise and mutation: consequence of evolutionary robustness

    Directory of Open Access Journals (Sweden)

    Kaneko Kunihiko

    2011-01-01

    Full Text Available Abstract Background Characterization of robustness and plasticity of phenotypes is a basic issue in evolutionary and developmental biology. The robustness and plasticity are concerned with changeability of a biological system against external perturbations. The perturbations are either genetic, i.e., due to mutations in genes in the population, or epigenetic, i.e., due to noise during development or environmental variations. Thus, the variances of phenotypes due to genetic and epigenetic perturbations provide quantitative measures for such changeability during evolution and development, respectively. Results Using numerical models simulating the evolutionary changes in the gene regulation network required to achieve a particular expression pattern, we first confirmed that gene expression dynamics robust to mutation evolved in the presence of a sufficient level of transcriptional noise. Under such conditions, the two types of variances in the gene expression levels, i.e. those due to mutations to the gene regulation network and those due to noise in gene expression dynamics were found to be proportional over a number of genes. The fraction of such genes with a common proportionality coefficient increased with an increase in the robustness of the evolved network. This proportionality was generally confirmed, also under the presence of environmental fluctuations and sexual recombination in diploids, and was explained from an evolutionary robustness hypothesis, in which an evolved robust system suppresses the so-called error catastrophe - the destabilization of the single-peaked distribution in gene expression levels. Experimental evidences for the proportionality of the variances over genes are also discussed. Conclusions The proportionality between the genetic and epigenetic variances of phenotypes implies the correlation between the robustness (or plasticity against genetic changes and against noise in development, and also suggests that

  19. Stability and robustness analysis of cooperation cycles driven by destructive agents in finite populations

    CERN Document Server

    Requejo, Rubén J; Cuesta, José A; Arenas, Alex; 10.1103/PhysRevE.86.026105

    2012-01-01

    The emergence and promotion of cooperation are two of the main issues in evolutionary game theory, as cooperation is amenable to exploitation by defectors, which take advantage of cooperative individuals at no cost, dooming them to extinction. It has been recently shown that the existence of purely destructive agents (termed jokers) acting on the common enterprises (public goods games) can induce stable limit cycles among cooperation, defection, and destruction when infinite populations are considered. These cycles allow for time lapses in which cooperators represent a relevant fraction of the population, providing a mechanism for the emergence of cooperative states in nature and human societies. Here we study analytically and through agent-based simulations the dynamics generated by jokers in finite populations for several selection rules. Cycles appear in all cases studied, thus showing that the joker dynamics generically yields a robust cyclic behavior not restricted to infinite populations. We also comput...

  20. Performance-Driven Robust Identification and Control of Uncertain Dynamical Systems

    Energy Technology Data Exchange (ETDEWEB)

    Basar, Tamer

    2001-10-29

    The grant DEFG02-97ER13939 from the Department of Energy has supported our research program on robust identification and control of uncertain dynamical systems, initially for the three-year period June 15, 1997-June 14, 2000, which was then extended on a no-cost basis for another year until June 14, 2001. This final report provides an overview of our research conducted during this period, along with a complete list of publications supported by the Grant. Within the scope of this project, we have studied fundamental issues that arise in modeling, identification, filtering, control, stabilization, control-based model reduction, decomposition and aggregation, and optimization of uncertain systems. The mathematical framework we have worked in has allowed the system dynamics to be only partially known (with the uncertainties being of both parametric or structural nature), and further the dynamics to be perturbed by unknown dynamic disturbances. Our research over these four years has generated a substantial body of new knowledge, and has led to new major developments in theory, applications, and computational algorithms. These have all been documented in various journal articles and book chapters, and have been presented at leading conferences, as to be described. A brief description of the results we have obtained within the scope of this project can be found in Section 3. To set the stage for the material of that section, we first provide in the next section (Section 2) a brief description of the issues that arise in the control of uncertain systems, and introduce several criteria under which optimality will lead to robustness and stability. Section 4 contains a list of references cited in these two sections. A list of our publications supported by the DOE Grant (covering the period June 15, 1997-June 14, 2001) comprises Section 5 of the report.

  1. Robust vibration control at critical resonant modes using indirect-driven self-sensing actuation in mechatronic systems.

    Science.gov (United States)

    Hong, Fan; Pang, Chee Khiang

    2012-11-01

    This paper presents an improved indirect-driven self-sensing actuation circuit for robust vibration control of piezoelectrically-actuated flexible structures in mechatronic systems. The circuit acts as a high-pass filter and provides better self-sensing strain signals with wider sensing bandwidth and higher signal-to-noise ratio. An adaptive non-model-based control is used to compensate for the structural vibrations using the strain signals from the circuit. The proposed scheme is implemented in a PZT-actuated suspension of a commercial dual-stage hard disk drive. Experimental results show improvements of 50% and 75% in the vibration suppression at 5.4kHz and 21kHz respectively, compared to the conventional PI control. Copyright © 2012 ISA. Published by Elsevier Ltd. All rights reserved.

  2. Robust modeling of differential gene expression data using normal/independent distributions: a Bayesian approach.

    Directory of Open Access Journals (Sweden)

    Mojtaba Ganjali

    Full Text Available In this paper, the problem of identifying differentially expressed genes under different conditions using gene expression microarray data, in the presence of outliers, is discussed. For this purpose, the robust modeling of gene expression data using some powerful distributions known as normal/independent distributions is considered. These distributions include the Student's t and normal distributions which have been used previously, but also include extensions such as the slash, the contaminated normal and the Laplace distributions. The purpose of this paper is to identify differentially expressed genes by considering these distributional assumptions instead of the normal distribution. A Bayesian approach using the Markov Chain Monte Carlo method is adopted for parameter estimation. Two publicly available gene expression data sets are analyzed using the proposed approach. The use of the robust models for detecting differentially expressed genes is investigated. This investigation shows that the choice of model for differentiating gene expression data is very important. This is due to the small number of replicates for each gene and the existence of outlying data. Comparison of the performance of these models is made using different statistical criteria and the ROC curve. The method is illustrated using some simulation studies. We demonstrate the flexibility of these robust models in identifying differentially expressed genes.

  3. Robust network oscillations during mammalian respiratory rhythm generation driven by synaptic dynamics.

    Science.gov (United States)

    Guerrier, Claire; Hayes, John A; Fortin, Gilles; Holcman, David

    2015-08-04

    How might synaptic dynamics generate synchronous oscillations in neuronal networks? We address this question in the preBötzinger complex (preBötC), a brainstem neural network that paces robust, yet labile, inspiration in mammals. The preBötC is composed of a few hundred neurons that alternate bursting activity with silent periods, but the mechanism underlying this vital rhythm remains elusive. Using a computational approach to model a randomly connected neuronal network that relies on short-term synaptic facilitation (SF) and depression (SD), we show that synaptic fluctuations can initiate population activities through recurrent excitation. We also show that a two-step SD process allows activity in the network to synchronize (bursts) and generate a population refractory period (silence). The model was validated against an array of experimental conditions, which recapitulate several processes the preBötC may experience. Consistent with the modeling assumptions, we reveal, by electrophysiological recordings, that SF/SD can occur at preBötC synapses on timescales that influence rhythmic population activity. We conclude that nondeterministic neuronal spiking and dynamic synaptic strengths in a randomly connected network are sufficient to give rise to regular respiratory-like rhythmic network activity and lability, which may play an important role in generating the rhythm for breathing and other coordinated motor activities in mammals.

  4. Robust Operation of Tendon-Driven Robot Fingers Using Force and Position-Based Control Laws

    Science.gov (United States)

    Abdallah, Muhammad E (Inventor); Platt, Jr., Robert J. (Inventor); Reiland, Matthew J (Inventor); Hargrave, Brian (Inventor); Diftler, Myron A (Inventor); Strawser, Philip A (Inventor); Ihrke, Chris A. (Inventor)

    2013-01-01

    A robotic system includes a tendon-driven finger and a control system. The system controls the finger via a force-based control law when a tension sensor is available, and via a position-based control law when a sensor is not available. Multiple tendons may each have a corresponding sensor. The system selectively injects a compliance value into the position-based control law when only some sensors are available. A control system includes a host machine and a non-transitory computer-readable medium having a control process, which is executed by the host machine to control the finger via the force- or position-based control law. A method for controlling the finger includes determining the availability of a tension sensor(s), and selectively controlling the finger, using the control system, via the force or position-based control law. The position control law allows the control system to resist disturbances while nominally maintaining the initial state of internal tendon tensions.

  5. Human Computation in Visualization: Using Purpose Driven Games for Robust Evaluation of Visualization Algorithms.

    Science.gov (United States)

    Ahmed, N; Zheng, Ziyi; Mueller, K

    2012-12-01

    Due to the inherent characteristics of the visualization process, most of the problems in this field have strong ties with human cognition and perception. This makes the human brain and sensory system the only truly appropriate evaluation platform for evaluating and fine-tuning a new visualization method or paradigm. However, getting humans to volunteer for these purposes has always been a significant obstacle, and thus this phase of the development process has traditionally formed a bottleneck, slowing down progress in visualization research. We propose to take advantage of the newly emerging field of Human Computation (HC) to overcome these challenges. HC promotes the idea that rather than considering humans as users of the computational system, they can be made part of a hybrid computational loop consisting of traditional computation resources and the human brain and sensory system. This approach is particularly successful in cases where part of the computational problem is considered intractable using known computer algorithms but is trivial to common sense human knowledge. In this paper, we focus on HC from the perspective of solving visualization problems and also outline a framework by which humans can be easily seduced to volunteer their HC resources. We introduce a purpose-driven game titled "Disguise" which serves as a prototypical example for how the evaluation of visualization algorithms can be mapped into a fun and addicting activity, allowing this task to be accomplished in an extensive yet cost effective way. Finally, we sketch out a framework that transcends from the pure evaluation of existing visualization methods to the design of a new one.

  6. Massive-scale gene co-expression network construction and robustness testing using random matrix theory.

    Science.gov (United States)

    Gibson, Scott M; Ficklin, Stephen P; Isaacson, Sven; Luo, Feng; Feltus, Frank A; Smith, Melissa C

    2013-01-01

    The study of gene relationships and their effect on biological function and phenotype is a focal point in systems biology. Gene co-expression networks built using microarray expression profiles are one technique for discovering and interpreting gene relationships. A knowledge-independent thresholding technique, such as Random Matrix Theory (RMT), is useful for identifying meaningful relationships. Highly connected genes in the thresholded network are then grouped into modules that provide insight into their collective functionality. While it has been shown that co-expression networks are biologically relevant, it has not been determined to what extent any given network is functionally robust given perturbations in the input sample set. For such a test, hundreds of networks are needed and hence a tool to rapidly construct these networks. To examine functional robustness of networks with varying input, we enhanced an existing RMT implementation for improved scalability and tested functional robustness of human (Homo sapiens), rice (Oryza sativa) and budding yeast (Saccharomyces cerevisiae). We demonstrate dramatic decrease in network construction time and computational requirements and show that despite some variation in global properties between networks, functional similarity remains high. Moreover, the biological function captured by co-expression networks thresholded by RMT is highly robust.

  7. Massive-scale gene co-expression network construction and robustness testing using random matrix theory.

    Directory of Open Access Journals (Sweden)

    Scott M Gibson

    Full Text Available The study of gene relationships and their effect on biological function and phenotype is a focal point in systems biology. Gene co-expression networks built using microarray expression profiles are one technique for discovering and interpreting gene relationships. A knowledge-independent thresholding technique, such as Random Matrix Theory (RMT, is useful for identifying meaningful relationships. Highly connected genes in the thresholded network are then grouped into modules that provide insight into their collective functionality. While it has been shown that co-expression networks are biologically relevant, it has not been determined to what extent any given network is functionally robust given perturbations in the input sample set. For such a test, hundreds of networks are needed and hence a tool to rapidly construct these networks. To examine functional robustness of networks with varying input, we enhanced an existing RMT implementation for improved scalability and tested functional robustness of human (Homo sapiens, rice (Oryza sativa and budding yeast (Saccharomyces cerevisiae. We demonstrate dramatic decrease in network construction time and computational requirements and show that despite some variation in global properties between networks, functional similarity remains high. Moreover, the biological function captured by co-expression networks thresholded by RMT is highly robust.

  8. Towards numerically robust multireference theories: The driven similarity renormalization group truncated to one- and two-body operators

    CERN Document Server

    Li, Chenyang

    2016-01-01

    The first nonperturbative version of the multireference driven similarity renormalization group (MR-DSRG) theory [C. Li and F. A. Evangelista, J. Chem. Theory Comput. $\\mathbf{11}$, 2097 (2015)] is introduced. The renormalization group structure of the MR-DSRG equations ensures numerical robustness and avoidance of the intruder state problem, while the connected nature of the amplitude and energy equations guarantees size consistency and extensivity. We approximate the MR-DSRG equations by keeping only one- and two-body operators and using a linearized recursive commutator approximation of the Baker--Campbell--Hausdorff expansion [T. Yanai and G. K.-L. Chan, J. Chem. Phys. $\\mathbf{124}$, 194106 (2006)]. The resulting MR-LDSRG(2) equations contain only 39 terms and scales as ${\\cal O}(N^2 N_{\\rm P}^2 N_{\\rm H}^2)$ where $N_{\\rm H}$, $N_{\\rm P}$, and $N$ correspond to the number of hole, particle, and total orbitals, respectively. Benchmark MR-LDSRG(2) computations on the hydrogen fluoride and molecular nitrog...

  9. ROBUST HYPERPARAMETER ESTIMATION PROTECTS AGAINST HYPERVARIABLE GENES AND IMPROVES POWER TO DETECT DIFFERENTIAL EXPRESSION

    Science.gov (United States)

    Phipson, Belinda; Lee, Stanley; Majewski, Ian J.; Alexander, Warren S.; Smyth, Gordon K.

    2017-01-01

    One of the most common analysis tasks in genomic research is to identify genes that are differentially expressed (DE) between experimental conditions. Empirical Bayes (EB) statistical tests using moderated genewise variances have been very effective for this purpose, especially when the number of biological replicate samples is small. The EB procedures can however be heavily influenced by a small number of genes with very large or very small variances. This article improves the differential expression tests by robustifying the hyperparameter estimation procedure. The robust procedure has the effect of decreasing the informativeness of the prior distribution for outlier genes while increasing its informativeness for other genes. This effect has the double benefit of reducing the chance that hypervariable genes will be spuriously identified as DE while increasing statistical power for the main body of genes. The robust EB algorithm is fast and numerically stable. The procedure allows exact small-sample null distributions for the test statistics and reduces exactly to the original EB procedure when no outlier genes are present. Simulations show that the robustified tests have similar performance to the original tests in the absence of outlier genes but have greater power and robustness when outliers are present. The article includes case studies for which the robust method correctly identifies and downweights genes associated with hidden covariates and detects more genes likely to be scientifically relevant to the experimental conditions. The new procedure is implemented in the limma software package freely available from the Bioconductor repository.

  10. Robust Yet Fragile: Expression Noise, Protein Misfolding, and Gene Dosage in the Evolution of Genomes.

    Science.gov (United States)

    Pires, J Chris; Conant, Gavin C

    2016-11-23

    The complex manner in which organisms respond to changes in their gene dosage has long fascinated geneticists. Oddly, although the existence of dominance implies that dosage reductions often have mild phenotypes, extra copies of whole chromosomes (aneuploidy) are generally strongly deleterious. Even more paradoxically, an extra copy of the genome is better tolerated than is aneuploidy. We review the resolution of this paradox, highlighting the roles of biochemistry, protein aggregation, and disruption of cellular microstructure in that explanation. Returning to life's curious combination of robustness and sensitivity to dosage changes, we argue that understanding how biological robustness evolved makes these observations less inexplicable. We propose that noise in gene expression and evolutionary strategies for its suppression play a role in generating dosage phenotypes. Finally, we outline an unappreciated mechanism for the preservation of duplicate genes, namely preservation to limit expression noise, arguing that it is particularly relevant in polyploid organisms.

  11. Data-Driven Robust RVFLNs Modeling of a Blast Furnace Iron-Making Process Using Cauchy Distribution Weighted M-Estimation

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Ping; Lv, Youbin; Wang, Hong; Chai, Tianyou

    2017-09-01

    Optimal operation of a practical blast furnace (BF) ironmaking process depends largely on a good measurement of molten iron quality (MIQ) indices. However, measuring the MIQ online is not feasible using the available techniques. In this paper, a novel data-driven robust modeling is proposed for online estimation of MIQ using improved random vector functional-link networks (RVFLNs). Since the output weights of traditional RVFLNs are obtained by the least squares approach, a robustness problem may occur when the training dataset is contaminated with outliers. This affects the modeling accuracy of RVFLNs. To solve this problem, a Cauchy distribution weighted M-estimation based robust RFVLNs is proposed. Since the weights of different outlier data are properly determined by the Cauchy distribution, their corresponding contribution on modeling can be properly distinguished. Thus robust and better modeling results can be achieved. Moreover, given that the BF is a complex nonlinear system with numerous coupling variables, the data-driven canonical correlation analysis is employed to identify the most influential components from multitudinous factors that affect the MIQ indices to reduce the model dimension. Finally, experiments using industrial data and comparative studies have demonstrated that the obtained model produces a better modeling and estimating accuracy and stronger robustness than other modeling methods.

  12. Data-driven asthma endotypes defined from blood biomarker and gene expression data

    Science.gov (United States)

    The diagnosis and treatment of childhood asthma is complicated by its mechanistically distinct subtypes (endotypes) driven by genetic susceptibility and modulating environmental factors. Clinical biomarkers and blood gene expression were collected from a stratified, cross-section...

  13. Robust Facial Expression Recognition via Sparse Representation and Multiple Gabor filters

    Directory of Open Access Journals (Sweden)

    Rania Salah El-Sayed

    2013-04-01

    Full Text Available Facial expressions recognition plays important role in human communication. It has become one of the most challenging tasks in the pattern recognition field. It has many applications such as: human computer interaction, video surveillance, forensic applications, criminal investigations, and in many other fields. In this paper we propose a method for facial expression recognition (FER. This method provides new insights into two issues in FER: feature extraction and robustness. For feature extraction we are using sparse representation approach after applying multiple Gabor filter and then using support vector machine (SVM as classifier. We conduct extensive experiments on standard facial expressions database to verify the performance of proposed method. And we compare the result with other approach.

  14. Order Under Uncertainty: Robust Differential Expression Analysis Using Probabilistic Models for Pseudotime Inference

    Science.gov (United States)

    Campbell, Kieran R.

    2016-01-01

    Single cell gene expression profiling can be used to quantify transcriptional dynamics in temporal processes, such as cell differentiation, using computational methods to label each cell with a ‘pseudotime’ where true time series experimentation is too difficult to perform. However, owing to the high variability in gene expression between individual cells, there is an inherent uncertainty in the precise temporal ordering of the cells. Pre-existing methods for pseudotime estimation have predominantly given point estimates precluding a rigorous analysis of the implications of uncertainty. We use probabilistic modelling techniques to quantify pseudotime uncertainty and propagate this into downstream differential expression analysis. We demonstrate that reliance on a point estimate of pseudotime can lead to inflated false discovery rates and that probabilistic approaches provide greater robustness and measures of the temporal resolution that can be obtained from pseudotime inference. PMID:27870852

  15. Robust stratification of breast cancer subtypes using differential patterns of transcript isoform expression.

    Directory of Open Access Journals (Sweden)

    Thomas P Stricker

    2017-03-01

    Full Text Available Breast cancer, the second leading cause of cancer death of women worldwide, is a heterogenous disease with multiple different subtypes. These subtypes carry important implications for prognosis and therapy. Interestingly, it is known that these different subtypes not only have different biological behaviors, but also have distinct gene expression profiles. However, it has not been rigorously explored whether particular transcriptional isoforms are also differentially expressed among breast cancer subtypes, or whether transcript isoforms from the same sets of genes can be used to differentiate subtypes. To address these questions, we analyzed the patterns of transcript isoform expression using a small set of RNA-sequencing data for eleven Estrogen Receptor positive (ER+ subtype and fourteen triple negative (TN subtype tumors. We identified specific sets of isoforms that distinguish these tumor subtypes with higher fidelity than standard mRNA expression profiles. We found that alternate promoter usage, alternative splicing, and alternate 3'UTR usage are differentially regulated in breast cancer subtypes. Profiling of isoform expression in a second, independent cohort of 68 tumors confirmed that expression of splice isoforms differentiates breast cancer subtypes. Furthermore, analysis of RNAseq data from 594 cases from the TCGA cohort confirmed the ability of isoform usage to distinguish breast cancer subtypes. Also using our expression data, we identified several RNA processing factors that were differentially expressed between tumor subtypes and/or regulated by estrogen receptor, including YBX1, YBX2, MAGOH, MAGOHB, and PCBP2. RNAi knock-down of these RNA processing factors in MCF7 cells altered isoform expression. These results indicate that global dysregulation of splicing in breast cancer occurs in a subtype-specific and reproducible manner and is driven by specific differentially expressed RNA processing factors.

  16. Performance driven expression mapping based on segmented examples

    Institute of Scientific and Technical Information of China (English)

    YING Shuang; ZHANG Qiang; ZHO U Dongsheng

    2012-01-01

    We present a method that combines performance-driven method with segmented 3D blendshape models to animate a face. First we prepare key sample examples and corresponding key target examples. Next we segment the whole face into two regions, for each region we reduce dimensionality of source examples using PAC into abstract space which is defined by truncated PCA eigen- vectors. Then for each example we fix the cardinal base function, which can determine the weight of the target example. Finally, in the animation stage we compute the weight of each example for each frame and add the weighted displacement vectors of each re- gion on the general face model.

  17. Ontology-Driven Co-clustering of Gene Expression Data

    Science.gov (United States)

    Cordero, Francesca; Pensa, Ruggero G.; Visconti, Alessia; Ienco, Dino; Botta, Marco

    The huge volume of gene expression data produced by microarrays and other high-throughput techniques has encouraged the development of new computational techniques to evaluate the data and to formulate new biological hypotheses. To this purpose, co-clustering techniques are widely used: these identify groups of genes that show similar activity patterns under a specific subset of the experimental conditions by measuring the similarity in expression within these groups. However, in many applications, distance metrics based only on expression levels fail in capturing biologically meaningful clusters.

  18. Robust H(∞) positional control of 2-DOF robotic arm driven by electro-hydraulic servo system.

    Science.gov (United States)

    Guo, Qing; Yu, Tian; Jiang, Dan

    2015-11-01

    In this paper an H∞ positional feedback controller is developed to improve the robust performance under structural and parametric uncertainty disturbance in electro-hydraulic servo system (EHSS). The robust control model is described as the linear state-space equation by upper linear fractional transformation. According to the solution of H∞ sub-optimal control problem, the robust controller is designed and simplified to lower order linear model which is easily realized in EHSS. The simulation and experimental results can validate the robustness of this proposed method. The comparison result with PI control shows that the robust controller is suitable for this EHSS under the critical condition where the desired system bandwidth is higher and the external load of the hydraulic actuator is closed to its limited capability. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

  19. A simple and robust vector-based shRNA expression system used for RNA interference.

    Directory of Open Access Journals (Sweden)

    Xue-jun Wang

    Full Text Available BACKGROUND: RNA interference (RNAi mediated by small interfering RNAs (siRNAs or short hairpin RNAs (shRNAs has become a powerful genetic tool for conducting functional studies. Previously, vector-based shRNA-expression strategies capable of inducing RNAi in viable cells have been developed, however, these vector systems have some disadvantages, either because they were error-prone or cost prohibitive. RESULTS: In this report we described the development of a simple, robust shRNA expression system utilizing 1 long oligonucleotide or 2 short oligonucleotides for half the cost of conventional shRNA construction methods and with a >95% cloning success rate. The shRNA loop sequence and stem structure were also compared and carefully selected for better RNAi efficiency. Furthermore, an easier strategy was developed based on isocaudomers which permit rapid combination of the most efficient promoter-shRNA cassettes. Finally, using this method, the conservative target sites for hepatitis B virus (HBV knockdown were systemically screened and HBV antigen expression shown to be successfully suppressed in the presence of connected multiple shRNAs both in vitro and in vivo. CONCLUSION: This novel design describes an inexpensive and effective way to clone and express single or multiple shRNAs from the same vector with the capacity for potent and effective silencing of target genes.

  20. Indirect two-sided relative ranking: a robust similarity measure for gene expression data

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    Licamele Louis

    2010-03-01

    Full Text Available Abstract Background There is a large amount of gene expression data that exists in the public domain. This data has been generated under a variety of experimental conditions. Unfortunately, these experimental variations have generally prevented researchers from accurately comparing and combining this wealth of data, which still hides many novel insights. Results In this paper we present a new method, which we refer to as indirect two-sided relative ranking, for comparing gene expression profiles that is robust to variations in experimental conditions. This method extends the current best approach, which is based on comparing the correlations of the up and down regulated genes, by introducing a comparison based on the correlations in rankings across the entire database. Because our method is robust to experimental variations, it allows a greater variety of gene expression data to be combined, which, as we show, leads to richer scientific discoveries. Conclusions We demonstrate the benefit of our proposed indirect method on several datasets. We first evaluate the ability of the indirect method to retrieve compounds with similar therapeutic effects across known experimental barriers, namely vehicle and batch effects, on two independent datasets (one private and one public. We show that our indirect method is able to significantly improve upon the previous state-of-the-art method with a substantial improvement in recall at rank 10 of 97.03% and 49.44%, on each dataset, respectively. Next, we demonstrate that our indirect method results in improved accuracy for classification in several additional datasets. These datasets demonstrate the use of our indirect method for classifying cancer subtypes, predicting drug sensitivity/resistance, and classifying (related cell types. Even in the absence of a known (i.e., labeled experimental barrier, the improvement of the indirect method in each of these datasets is statistically significant.

  1. PolI-driven integrative expression vectors for yeast.

    Science.gov (United States)

    Blancafort, P; Ferbeyre, G; Sariol, C; Cedergren, R

    1997-07-23

    A novel expression vector for yeast has been constructed from the regulatory elements present in the polI promoter and the enhancer/termination region (E/T) of rDNA. Under some conditions, this promoter/vector combination produces small RNAs such as the hammerhead RNA sequence at levels comparable to polII- and polIII-dependent systems. No stable transcription product can be demonstrated with this vector when the enhancer/termination sequence is less than 100 nucleotides downstream from the promoter. On the other hand, high expression of a stable, hammerhead RNA molecule can be obtained from this vector by inserting a 400-bp fragment containing the ADH1 transcription termination region upstream of the E/T. RNAs produced by this vector are polyadenylated and multiple copies of this plasmid can be stably integrated into the yeast chromosome.

  2. Poinsettia protoplasts - a simple, robust and efficient system for transient gene expression studies

    Directory of Open Access Journals (Sweden)

    Pitzschke Andrea

    2012-05-01

    Full Text Available Abstract Background Transient gene expression systems are indispensable tools in molecular biology. Yet, their routine application is limited to few plant species often requiring substantial equipment and facilities. High chloroplast and chlorophyll content may further impede downstream applications of transformed cells from green plant tissue. Results Here, we describe a fast and simple technique for the high-yield isolation and efficient transformation (>70% of mesophyll-derived protoplasts from red leaves of the perennial plant Poinsettia (Euphorbia pulccherrima. In this method no particular growth facilities or expensive equipments are needed. Poinsettia protoplasts display an astonishing robustness and can be employed in a variety of commonly-used downstream applications, such as subcellular localisation (multi-colour fluorescence or promoter activity studies. Due to low abundance of chloroplasts or chromoplasts, problems encountered in other mesophyll-derived protoplast systems (particularly autofluorescence are alleviated. Furthermore, the transgene expression is detectable within 90 minutes of transformation and lasts for several days. Conclusions The simplicity of the isolation and transformation procedure renders Poinsettia protoplasts an attractive system for transient gene expression experiments, including multi-colour fluorescence, subcellular localisation and promoter activity studies. In addition, they offer hitherto unknown possibilities for anthocyan research and industrial applications.

  3. Automated optogenetic feedback control for precise and robust regulation of gene expression and cell growth

    Science.gov (United States)

    Milias-Argeitis, Andreas; Rullan, Marc; Aoki, Stephanie K.; Buchmann, Peter; Khammash, Mustafa

    2016-01-01

    Dynamic control of gene expression can have far-reaching implications for biotechnological applications and biological discovery. Thanks to the advantages of light, optogenetics has emerged as an ideal technology for this task. Current state-of-the-art methods for optical expression control fail to combine precision with repeatability and cannot withstand changing operating culture conditions. Here, we present a novel fully automatic experimental platform for the robust and precise long-term optogenetic regulation of protein production in liquid Escherichia coli cultures. Using a computer-controlled light-responsive two-component system, we accurately track prescribed dynamic green fluorescent protein expression profiles through the application of feedback control, and show that the system adapts to global perturbations such as nutrient and temperature changes. We demonstrate the efficacy and potential utility of our approach by placing a key metabolic enzyme under optogenetic control, thus enabling dynamic regulation of the culture growth rate with potential applications in bacterial physiology studies and biotechnology. PMID:27562138

  4. Conserved Cis-Regulatory Modules Control Robustness in Msx1 Expression at Single-Cell Resolution

    Science.gov (United States)

    Vance, Keith W.; Woodcock, Dan J.; Reid, John E.; Bretschneider, Till; Ott, Sascha; Koentges, Georgy

    2015-01-01

    The process of transcription is highly stochastic leading to cell-to-cell variations and noise in gene expression levels. However, key essential genes have to be precisely expressed at the correct amount and time to ensure proper cellular development and function. Studies in yeast and bacterial systems have shown that gene expression noise decreases as mean expression levels increase, a relationship that is controlled by promoter DNA sequence. However, the function of distal cis-regulatory modules (CRMs), an evolutionary novelty of metazoans, in controlling transcriptional robustness and variability is poorly understood. In this study, we used live cell imaging of transfected reporters combined with a mathematical modelling and statistical inference scheme to quantify the function of conserved Msx1 CRMs and promoters in modulating single-cell real-time transcription rates in C2C12 mouse myoblasts. The results show that the mean expression–noise relationship is solely promoter controlled for this key pluripotency regulator. In addition, we demonstrate that CRMs modulate single-cell basal promoter rate distributions in a graded manner across a population of cells. This extends the rheostatic model of CRM action to provide a more detailed understanding of CRM function at single-cell resolution. We also identify a novel CRM transcriptional filter function that acts to reduce intracellular variability in transcription rates and show that this can be phylogenetically separable from rate modulating CRM activities. These results are important for understanding how the expression of key vertebrate developmental transcription factors is precisely controlled both within and between individual cells. PMID:26342140

  5. Robust detection of hierarchical communities from Escherichia coli gene expression data.

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    Santiago Treviño

    Full Text Available Determining the functional structure of biological networks is a central goal of systems biology. One approach is to analyze gene expression data to infer a network of gene interactions on the basis of their correlated responses to environmental and genetic perturbations. The inferred network can then be analyzed to identify functional communities. However, commonly used algorithms can yield unreliable results due to experimental noise, algorithmic stochasticity, and the influence of arbitrarily chosen parameter values. Furthermore, the results obtained typically provide only a simplistic view of the network partitioned into disjoint communities and provide no information of the relationship between communities. Here, we present methods to robustly detect co-regulated and functionally enriched gene communities and demonstrate their application and validity for Escherichia coli gene expression data. Applying a recently developed community detection algorithm to the network of interactions identified with the context likelihood of relatedness (CLR method, we show that a hierarchy of network communities can be identified. These communities significantly enrich for gene ontology (GO terms, consistent with them representing biologically meaningful groups. Further, analysis of the most significantly enriched communities identified several candidate new regulatory interactions. The robustness of our methods is demonstrated by showing that a core set of functional communities is reliably found when artificial noise, modeling experimental noise, is added to the data. We find that noise mainly acts conservatively, increasing the relatedness required for a network link to be reliably assigned and decreasing the size of the core communities, rather than causing association of genes into new communities.

  6. Feasibility and robustness of dose painting by numbers in proton therapy with contour-driven plan optimization

    Energy Technology Data Exchange (ETDEWEB)

    Barragán, A. M., E-mail: ana.barragan@uclouvain.be; Differding, S.; Lee, J. A.; Sterpin, E. [Center of Molecular Imaging, Radiotherapy and Oncology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels B-1200 (Belgium); Janssens, G. [Ion Beam Applications S.A., Louvain-la-Neuve 1348 (Belgium)

    2015-04-15

    Purpose: To prove the ability of protons to reproduce a dose gradient that matches a dose painting by numbers (DPBN) prescription in the presence of setup and range errors, by using contours and structure-based optimization in a commercial treatment planning system. Methods: For two patients with head and neck cancer, voxel-by-voxel prescription to the target volume (GTV{sub PET}) was calculated from {sup 18}FDG-PET images and approximated with several discrete prescription subcontours. Treatments were planned with proton pencil beam scanning. In order to determine the optimal plan parameters to approach the DPBN prescription, the effects of the scanning pattern, number of fields, number of subcontours, and use of range shifter were separately tested on each patient. Different constant scanning grids (i.e., spot spacing = Δx = Δy = 3.5, 4, and 5 mm) and uniform energy layer separation [4 and 5 mm WED (water equivalent distance)] were analyzed versus a dynamic and automatic selection of the spots grid. The number of subcontours was increased from 3 to 11 while the number of beams was set to 3, 5, or 7. Conventional PTV-based and robust clinical target volumes (CTV)-based optimization strategies were considered and their robustness against range and setup errors assessed. Because of the nonuniform prescription, ensuring robustness for coverage of GTV{sub PET} inevitably leads to overdosing, which was compared for both optimization schemes. Results: The optimal number of subcontours ranged from 5 to 7 for both patients. All considered scanning grids achieved accurate dose painting (1% average difference between the prescribed and planned doses). PTV-based plans led to nonrobust target coverage while robust-optimized plans improved it considerably (differences between worst-case CTV dose and the clinical constraint was up to 3 Gy for PTV-based plans and did not exceed 1 Gy for robust CTV-based plans). Also, only 15% of the points in the GTV{sub PET} (worst case) were

  7. Robust Inference of Cell-to-Cell Expression Variations from Single- and K-Cell Profiling.

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    Manikandan Narayanan

    2016-07-01

    Full Text Available Quantifying heterogeneity in gene expression among single cells can reveal information inaccessible to cell-population averaged measurements. However, the expression level of many genes in single cells fall below the detection limit of even the most sensitive technologies currently available. One proposed approach to overcome this challenge is to measure random pools of k cells (e.g., 10 to increase sensitivity, followed by computational "deconvolution" of cellular heterogeneity parameters (CHPs, such as the biological variance of single-cell expression levels. Existing approaches infer CHPs using either single-cell or k-cell data alone, and typically within a single population of cells. However, integrating both single- and k-cell data may reap additional benefits, and quantifying differences in CHPs across cell populations or conditions could reveal novel biological information. Here we present a Bayesian approach that can utilize single-cell, k-cell, or both simultaneously to infer CHPs within a single condition or their differences across two conditions. Using simulated as well as experimentally generated single- and k-cell data, we found situations where each data type would offer advantages, but using both together can improve precision and better reconcile CHP information contained in single- and k-cell data. We illustrate the utility of our approach by applying it to jointly generated single- and k-cell data to reveal CHP differences in several key inflammatory genes between resting and inflammatory cytokine-activated human macrophages, delineating differences in the distribution of 'ON' versus 'OFF' cells and in continuous variation of expression level among cells. Our approach thus offers a practical and robust framework to assess and compare cellular heterogeneity within and across biological conditions using modern multiplexed technologies.

  8. Gene Expression Noise Enhances Robust Organization of the Early Mammalian Blastocyst

    Science.gov (United States)

    Wang, Qixuan; Du, Huijing; Peng, Tao; Chiang, Michael; Cinquin, Olivier; Cho, Ken

    2017-01-01

    A critical event in mammalian embryo development is construction of an inner cell mass surrounded by a trophoectoderm (a shell of cells that later form extraembryonic structures). We utilize multi-scale, stochastic modeling to investigate the design principles responsible for robust establishment of these structures. This investigation makes three predictions, each supported by our quantitative imaging. First, stochasticity in the expression of critical genes promotes cell plasticity and has a critical role in accurately organizing the developing mouse blastocyst. Second, asymmetry in the levels of noise variation (expression fluctuation) of Cdx2 and Oct4 provides a means to gain the benefits of noise-mediated plasticity while ameliorating the potentially detrimental effects of stochasticity. Finally, by controlling the timing and pace of cell fate specification, the embryo temporally modulates plasticity and creates a time window during which each cell can continually read its environment and adjusts its fate. These results suggest noise has a crucial role in maintaining cellular plasticity and organizing the blastocyst. PMID:28114387

  9. A robust dual reporter system to visualize and quantify gene expression mediated by transcription activator-like effectors

    Directory of Open Access Journals (Sweden)

    Uhde-Stone Claudia

    2012-08-01

    Full Text Available Abstract Background Transcription activator-like effectors (TALEs are a class of naturally occurring transcription effectors that recognize specific DNA sequences and modulate gene expression. The modularity of TALEs DNA binding domain enables sequence-specific perturbation and offers broad applications in genetic and epigenetic studies. Although the efficient construction of TALEs has been established, robust functional tools to assess their functions remain lacking. Results We established a dual reporter system that was specifically designed for real-time monitoring and quantifying gene expression mediated by TALEs. We validated both sensitivity and specificity of this dual-reporter system in mammalian cells, and demonstrated that this dual reporter system is robust and potentially amenable to high throughput (HTP applications. Conclusion We have designed, constructed and validated a novel dual reporter system for assessing TALE mediated gene regulations. This system offers a robust and easy-to- use tool for real-time monitoring and quantifying gene expression in mammalian cells.

  10. Robust TLR4-induced gene expression patterns are not an accurate indicator of human immunity

    Science.gov (United States)

    2010-01-01

    Background Activation of Toll-like receptors (TLRs) is widely accepted as an essential event for defence against infection. Many TLRs utilize a common signalling pathway that relies on activation of the kinase IRAK4 and the transcription factor NFκB for the rapid expression of immunity genes. Methods 21 K DNA microarray technology was used to evaluate LPS-induced (TLR4) gene responses in blood monocytes from a child with an IRAK4-deficiency. In vitro responsiveness to LPS was confirmed by real-time PCR and ELISA and compared to the clinical predisposition of the child and IRAK4-deficient mice to Gram negative infection. Results We demonstrated that the vast majority of LPS-responsive genes in IRAK4-deficient monocytes were greatly suppressed, an observation that is consistent with the described role for IRAK4 as an essential component of TLR4 signalling. The severely impaired response to LPS, however, is inconsistent with a remarkably low incidence of Gram negative infections observed in this child and other children with IRAK4-deficiency. This unpredicted clinical phenotype was validated by demonstrating that IRAK4-deficient mice had a similar resistance to infection with Gram negative S. typhimurium as wildtype mice. A number of immunity genes, such as chemokines, were expressed at normal levels in human IRAK4-deficient monocytes, indicating that particular IRAK4-independent elements within the repertoire of TLR4-induced responses are expressed. Conclusions Sufficient defence to Gram negative immunity does not require IRAK4 or a robust, 'classic' inflammatory and immune response. PMID:20105294

  11. The contribution of tumor and host tissue factor expression to oncogene-driven gliomagenesis.

    Science.gov (United States)

    Magnus, Nathalie; Meehan, Brian; Garnier, Delphine; Hashemi, Maryam; Montermini, Laura; Lee, Tae Hoon; Milsom, Chloe; Pawlinski, Rafal; Ohlfest, John; Anderson, Mark; Mackman, Nigel; Rak, Janusz

    2014-11-14

    Glioblastoma multiforme (GBM) is an aggressive form of glial brain tumors, associated with angiogenesis, thrombosis, and upregulation of tissue factor (TF), the key cellular trigger of coagulation and signaling. Since TF is upregulated by oncogenic mutations occurring in different subsets of human brain tumors we investigated whether TF contributes to tumourigenesis driven by oncogenic activation of EGFR (EGFRvIII) and RAS pathways in the brain. Here we show that TF expression correlates with poor prognosis in glioma, but not in GBM. In situ, the TF protein expression is heterogeneously expressed in adult and pediatric gliomas. GBM cells harboring EGFRvIII (U373vIII) grow aggressively as xenografts in SCID mice and their progression is delayed by administration of monoclonal antibodies blocking coagulant (CNTO 859) and signaling (10H10) effects of TF in vivo. Mice in which TF gene is disrupted in the neuroectodermal lineage exhibit delayed progression of spontaneous brain tumors driven by oncogenic N-ras and SV40 large T antigen (SV40LT) expressed under the control of sleeping beauty transposase. Reduced host TF levels in low-TF/SCID hypomorphic mice mitigated growth of glioma subcutaneously but not in the brain. Thus, we suggest that tumor-associated TF may serve as therapeutic target in the context of oncogene-driven disease progression in a subset of glioma.

  12. A Hybrid One-Way ANOVA Approach for the Robust and Efficient Estimation of Differential Gene Expression with Multiple Patterns.

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    Mohammad Manir Hossain Mollah

    Full Text Available Identifying genes that are differentially expressed (DE between two or more conditions with multiple patterns of expression is one of the primary objectives of gene expression data analysis. Several statistical approaches, including one-way analysis of variance (ANOVA, are used to identify DE genes. However, most of these methods provide misleading results for two or more conditions with multiple patterns of expression in the presence of outlying genes. In this paper, an attempt is made to develop a hybrid one-way ANOVA approach that unifies the robustness and efficiency of estimation using the minimum β-divergence method to overcome some problems that arise in the existing robust methods for both small- and large-sample cases with multiple patterns of expression.The proposed method relies on a β-weight function, which produces values between 0 and 1. The β-weight function with β = 0.2 is used as a measure of outlier detection. It assigns smaller weights (≥ 0 to outlying expressions and larger weights (≤ 1 to typical expressions. The distribution of the β-weights is used to calculate the cut-off point, which is compared to the observed β-weight of an expression to determine whether that gene expression is an outlier. This weight function plays a key role in unifying the robustness and efficiency of estimation in one-way ANOVA.Analyses of simulated gene expression profiles revealed that all eight methods (ANOVA, SAM, LIMMA, EBarrays, eLNN, KW, robust BetaEB and proposed perform almost identically for m = 2 conditions in the absence of outliers. However, the robust BetaEB method and the proposed method exhibited considerably better performance than the other six methods in the presence of outliers. In this case, the BetaEB method exhibited slightly better performance than the proposed method for the small-sample cases, but the the proposed method exhibited much better performance than the BetaEB method for both the small- and large

  13. Rapid expression of transgenes driven by seed-specific constructs in leaf tissue: DHA production

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    Zhou Xue-Rong

    2010-03-01

    Full Text Available Abstract Background Metabolic engineering of seed biosynthetic pathways to diversify and improve crop product quality is a highly active research area. The validation of genes driven by seed-specific promoters is time-consuming since the transformed plants must be grown to maturity before the gene function can be analysed. Results In this study we demonstrate that genes driven by seed-specific promoters contained within complex constructs can be transiently-expressed in the Nicotiana benthamiana leaf-assay system by co-infiltrating the Arabidopsis thaliana LEAFY COTYLEDON2 (LEC2 gene. A real-world case study is described in which we first assembled an efficient transgenic DHA synthesis pathway using a traditional N. benthamiana Cauliflower Mosaic Virus (CaMV 35S-driven leaf assay before using the LEC2-extended assay to rapidly validate a complex seed-specific construct containing the same genes before stable transformation in Arabidopsis. Conclusions The LEC2-extended N. benthamiana assay allows the transient activation of seed-specific promoters in leaf tissue. In this study we have used the assay as a rapid preliminary screen of a complex seed-specific transgenic construct prior to stable transformation, a feature that will become increasingly useful as genetic engineering moves from the manipulation of single genes to the engineering of complex pathways. We propose that the assay will prove useful for other applications wherein rapid expression of transgenes driven by seed-specific constructs in leaf tissue are sought.

  14. Dynamic modelling and robust current control of wind-turbine driven DFIG during external AC voltage dip

    Institute of Scientific and Technical Information of China (English)

    HU Jia-bing; HE Yi-kang

    2006-01-01

    Doubly-FedInduction Generator (DFIG), with vector control applied, is widely used in Variable-Speed ConstantFrequency (VSCF) windenergy generation system and shows good performance in maximum wind energy capture. But in two traditional vector control schemes, the equivalent stator magnetizing current is considered invariant in order to simplify the rotor current inner-loop controller. The two schemes can perform very well when the grid is in normal condition. However, when grid disturbance such as grid voltage dip or swell fault occurs, the control performance worsens, the rotor over current occurs and the Fault Ride-Through (FRT) capability of the DFIG wind energy generation system gets seriously deteriorated. An accurate DFIG model was used to deeply investigate the deficiency of the traditional vector control. The improved control schemes of two typical traditional vector control schemes used in DFIG were proposed, and simulation study of the proposed and traditional control schemes, with robust rotor current control using Internal Model Control (IMC) method, was carried out. The validity of the proposed modified schemes to control the rotor current and to improve the FRT capability of the DFIG wind energy generation system was proved by the comparison study.

  15. Neuronal MHC Class I Expression Is Regulated by Activity Driven Calcium Signaling.

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    Dan Lv

    Full Text Available MHC class I (MHC-I molecules are important components of the immune system. Recently MHC-I have been reported to also play important roles in brain development and synaptic plasticity. In this study, we examine the molecular mechanism(s underlying activity-dependent MHC-I expression using hippocampal neurons. Here we report that neuronal expression level of MHC-I is dynamically regulated during hippocampal development after birth in vivo. Kainic acid (KA treatment significantly increases the expression of MHC-I in cultured hippocampal neurons in vitro, suggesting that MHC-I expression is regulated by neuronal activity. In addition, KA stimulation decreased the expression of pre- and post-synaptic proteins. This down-regulation is prevented by addition of an MHC-I antibody to KA treated neurons. Further studies demonstrate that calcium-dependent protein kinase C (PKC is important in relaying KA simulation activation signals to up-regulated MHC-I expression. This signaling cascade relies on activation of the MAPK pathway, which leads to increased phosphorylation of CREB and NF-κB p65 while also enhancing the expression of IRF-1. Together, these results suggest that expression of MHC-I in hippocampal neurons is driven by Ca2+ regulated activation of the MAPK signaling transduction cascade.

  16. Data-driven asthma endotypes defined from blood biomarker and gene expression data.

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    Barbara Jane George

    Full Text Available The diagnosis and treatment of childhood asthma is complicated by its mechanistically distinct subtypes (endotypes driven by genetic susceptibility and modulating environmental factors. Clinical biomarkers and blood gene expression were collected from a stratified, cross-sectional study of asthmatic and non-asthmatic children from Detroit, MI. This study describes four distinct asthma endotypes identified via a purely data-driven method. Our method was specifically designed to integrate blood gene expression and clinical biomarkers in a way that provides new mechanistic insights regarding the different asthma endotypes. For example, we describe metabolic syndrome-induced systemic inflammation as an associated factor in three of the four asthma endotypes. Context provided by the clinical biomarker data was essential in interpreting gene expression patterns and identifying putative endotypes, which emphasizes the importance of integrated approaches when studying complex disease etiologies. These synthesized patterns of gene expression and clinical markers from our research may lead to development of novel serum-based biomarker panels.

  17. The impact of gene expression variation on the robustness and evolvability of a developmental gene regulatory network.

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    David A Garfield

    2013-10-01

    Full Text Available Regulatory interactions buffer development against genetic and environmental perturbations, but adaptation requires phenotypes to change. We investigated the relationship between robustness and evolvability within the gene regulatory network underlying development of the larval skeleton in the sea urchin Strongylocentrotus purpuratus. We find extensive variation in gene expression in this network throughout development in a natural population, some of which has a heritable genetic basis. Switch-like regulatory interactions predominate during early development, buffer expression variation, and may promote the accumulation of cryptic genetic variation affecting early stages. Regulatory interactions during later development are typically more sensitive (linear, allowing variation in expression to affect downstream target genes. Variation in skeletal morphology is associated primarily with expression variation of a few, primarily structural, genes at terminal positions within the network. These results indicate that the position and properties of gene interactions within a network can have important evolutionary consequences independent of their immediate regulatory role.

  18. Allen Brain Atlas-Driven Visualizations: A Web-Based Gene Expression Energy Visualization Tool

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    Andrew eZaldivar

    2014-05-01

    Full Text Available The Allen Brain Atlas-Driven Visualizations (ABADV is a publicly accessible web-based tool created to retrieve and visualize expression energy data from the Allen Brain Atlas (ABA across multiple genes and brain structures. Though the ABA offers their own search engine and software for researchers to view their growing collection of online public data sets, including extensive gene expression and neuroanatomical data from human and mouse brain, many of their tools limit the amount of genes and brain structures researchers can view at once. To complement their work, ABADV generates multiple pie charts, bar charts and heat maps of expression energy values for any given set of genes and brain structures. Such a suite of free and easy-to-understand visualizations allows for easy comparison of gene expression across multiple brain areas. In addition, each visualization links back to the ABA so researchers may view a summary of the experimental detail. ABADV is currently supported on modern web browsers and is compatible with expression energy data from the Allen Mouse Brain Atlas in situ hybridization data. By creating this web application, researchers can immediately obtain and survey numerous amounts of expression energy data from the ABA, which they can then use to supplement their work or perform meta-analysis. In the future, we hope to enable ABADV across multiple data resources.

  19. Robust model reference adaptive control for a two-dimensional piezo-driven micro-displacement scanning platform based on the asymmetrical Bouc-Wen model

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    Haigen Yang

    2016-11-01

    Full Text Available The hysteresis characteristics resulted from piezoelectric actuators (PAs and the residual vibration in the rapid positioning of a two-dimensional piezo-driven micro-displacement scanning platform (2D-PDMDSP will greatly affect the positioning accuracy and speed. In this paper, in order to improve the accuracy and speed of the positioning and restrain the residual vibration of 2D-PDMDSP, firstly, Utilizing an online hysteresis observer based on the asymmetrical Bouc-Wen model, the PA with the hysteresis characteristics is feedforward linearized and can be used as a linear actuator; secondly, zero vibration and derivative shaping (ZVDS technique is used to eliminate the residual vibration of the 2D-PDMDSP; lastly, the robust model reference adaptive (RMRA control for the 2D-PDMDSP is proposed and explored. The rapid control prototype of the RMRA controller combining the proposed feedforward linearization and ZVDS control for the 2D-PDMDSP with rapid control prototyping technique based on the real-time simulation system is established and experimentally tested, and the corresponding controlled results are compared with those by the PID control method. The experimental results show that the proposed RMRA control method can significantly improve the accuracy and speed of the positioning and restrain the residual vibration of 2D-PDMDSP.

  20. Expression characteristics of GFP driven by NAC1 promoter and its responses to auxin and gibberellin

    Institute of Scientific and Technical Information of China (English)

    WANG Youhua; DUAN Liusheng; LU Mengzhu; LI Zhaohu; WANG Minjie; ZHAI Zhixi

    2006-01-01

    A 1050 bp fragment upstream transcription start site of a transcription factor gene NAC1 in Arabidopsis thaliana was amplified and cloned into plasmid pRD420 to construct a green fluorescent protein(GFP) fusion system under the control of NAC1 promoter. Plasmids were introduced into tobacco by Agrobacterium mediated method to regenerate plants with NAC1-GFP gene, and expression pattern of NAC1-GFP and its responses to auxin and gibberellin (GA) were observed. GFP was found to accumulate specifically in root, and was detected after treatment of auxin, N-1-Naphthylphthalamic acid (NPA, an auxin antagonist) or GA3. It was indicated that the expression of GFP driven by NAC1 promoter was induced not only by auxin but also by GAs, suggesting that NAC1 mediated both the auxin signaling and the GAs signaling involved in lateral roots development.

  1. Determinants of effective lentivirus-driven microRNA expression in vivo.

    Science.gov (United States)

    Mishima, Takuya; Sadovsky, Elena; Gegick, Margaret E; Sadovsky, Yoel

    2016-09-15

    Manipulation of microRNA (miRNA) levels, including overexpression of mature species, has become an important biological tool, even motivating miRNA-based therapeutics. To assess key determinants of miRNA overexpression in a mammalian system in vivo, we sought to bypass the laborious generation of a transgenic animal by exploiting placental trophoblast-specific gene manipulation using lentiviral vectors, which has been instrumental in elucidating trophoblast biology. We examined the impact of several key components of miRNA stem loops and their flanking sequences on the efficiency of mature miRNA expression in vivo. By combining established and novel approaches for miRNA expression, we engineered lentivirus-driven miRNA expression plasmids, which we tested in the mouse placenta. We found that reverse sense inserts minimized single-strand splicing and degradation, and that maintaining longer, poly-A-containing arms flanking the miRNA stem-loop markedly enhanced transgenic miRNA expression. Additionally, we accomplished overexpression of diverse mammalian, drosophila, or C. elegans miRNAs, either based on native context or using a "cassette" replacement of the mature miRNA sequence. Together, we have identified primary miRNA sequences that are paramount for effective expression of mature miRNAs, and validated their role in mice. Principles established by our findings may guide the design of efficient miRNA vectors for in vivo use.

  2. Expression robust 3D face recognition via mesh-based histograms of multiple order surface differential quantities

    KAUST Repository

    Li, Huibin

    2011-09-01

    This paper presents a mesh-based approach for 3D face recognition using a novel local shape descriptor and a SIFT-like matching process. Both maximum and minimum curvatures estimated in the 3D Gaussian scale space are employed to detect salient points. To comprehensively characterize 3D facial surfaces and their variations, we calculate weighted statistical distributions of multiple order surface differential quantities, including histogram of mesh gradient (HoG), histogram of shape index (HoS) and histogram of gradient of shape index (HoGS) within a local neighborhood of each salient point. The subsequent matching step then robustly associates corresponding points of two facial surfaces, leading to much more matched points between different scans of a same person than the ones of different persons. Experimental results on the Bosphorus dataset highlight the effectiveness of the proposed method and its robustness to facial expression variations. © 2011 IEEE.

  3. Specialized motor-driven dusp1 expression in the song systems of multiple lineages of vocal learning birds.

    Directory of Open Access Journals (Sweden)

    Haruhito Horita

    Full Text Available Mechanisms for the evolution of convergent behavioral traits are largely unknown. Vocal learning is one such trait that evolved multiple times and is necessary in humans for the acquisition of spoken language. Among birds, vocal learning is evolved in songbirds, parrots, and hummingbirds. Each time similar forebrain song nuclei specialized for vocal learning and production have evolved. This finding led to the hypothesis that the behavioral and neuroanatomical convergences for vocal learning could be associated with molecular convergence. We previously found that the neural activity-induced gene dual specificity phosphatase 1 (dusp1 was up-regulated in non-vocal circuits, specifically in sensory-input neurons of the thalamus and telencephalon; however, dusp1 was not up-regulated in higher order sensory neurons or motor circuits. Here we show that song motor nuclei are an exception to this pattern. The song nuclei of species from all known vocal learning avian lineages showed motor-driven up-regulation of dusp1 expression induced by singing. There was no detectable motor-driven dusp1 expression throughout the rest of the forebrain after non-vocal motor performance. This pattern contrasts with expression of the commonly studied activity-induced gene egr1, which shows motor-driven expression in song nuclei induced by singing, but also motor-driven expression in adjacent brain regions after non-vocal motor behaviors. In the vocal non-learning avian species, we found no detectable vocalizing-driven dusp1 expression in the forebrain. These findings suggest that independent evolutions of neural systems for vocal learning were accompanied by selection for specialized motor-driven expression of the dusp1 gene in those circuits. This specialized expression of dusp1 could potentially lead to differential regulation of dusp1-modulated molecular cascades in vocal learning circuits.

  4. Toroidal current profile control during low confinement mode plasma discharges in DIII-D via first-principles-driven model-based robust control synthesis

    Science.gov (United States)

    Barton, Justin E.; Boyer, Mark D.; Shi, Wenyu; Schuster, Eugenio; Luce, Tim C.; Ferron, John R.; Walker, Michael L.; Humphreys, David A.; Penaflor, Ben G.; Johnson, Robert D.

    2012-12-01

    In order for ITER to be capable of operating in advanced tokamak operating regimes, characterized by a high fusion gain, good plasma confinement, magnetohydrodynamic stability and a non-inductively driven plasma current, for extended periods of time, several challenging plasma control problems still need to be solved. Setting up a suitable toroidal current density profile in the tokamak is key for one possible advanced operating scenario characterized by non-inductive sustainment of the plasma current. At the DIII-D tokamak, the goal is to create the desired current profile during the ramp-up and early flat-top phases of the plasma discharge and then actively maintain this target profile for the remainder of the discharge. The evolution in time of the toroidal current profile in tokamaks is related to the evolution of the poloidal magnetic flux profile, which is modelled in normalized cylindrical coordinates using a first-principles, nonlinear, dynamic partial differential equation (PDE) referred to as the magnetic diffusion equation. The magnetic diffusion equation is combined with empirical correlations developed from physical observations and experimental data from DIII-D for the electron temperature, the plasma resistivity and the non-inductive current drive to develop a simplified, control-oriented, nonlinear, dynamic PDE model of the poloidal flux profile evolution valid for low confinement mode discharges. In this work, we synthesize a robust feedback controller to reject disturbances and track a desired reference trajectory of the poloidal magnetic flux gradient profile by employing the control-oriented model of the system. A singular value decomposition of the static gain matrix of the plant model is utilized to identify the most relevant control channels and is combined with the dynamic response of system around a given operating trajectory to design the feedback controller. A general framework for real-time feedforward + feedback control of magnetic and

  5. Erythroid-Specific Expression of LIN28A Is Sufficient for Robust Gamma-Globin Gene and Protein Expression in Adult Erythroblasts.

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    Y Terry Lee

    Full Text Available Increasing fetal hemoglobin (HbF levels in adult humans remains an active area in hematologic research. Here we explored erythroid-specific LIN28A expression for its effect in regulating gamma-globin gene expression and HbF levels in cultured adult erythroblasts. For this purpose, lentiviral transduction vectors were produced with LIN28A expression driven by erythroid-specific gene promoter regions of the human KLF1 or SPTA1 genes. Transgene expression of LIN28A with a linked puromycin resistance marker was restricted to the erythroid lineage as demonstrated by selective survival of erythroid colonies (greater than 95% of all colonies. Erythroblast LIN28A over-expression (LIN28A-OE did not significantly affect proliferation or inhibit differentiation. Greater than 70% suppression of total let-7 microRNA levels was confirmed in LIN28A-OE cells. Increases in gamma-globin mRNA and protein expression with HbF levels reaching 30-40% were achieved. These data suggest that erythroblast targeting of LIN28A expression is sufficient for increasing fetal hemoglobin expression in adult human erythroblasts.

  6. Erythroid-Specific Expression of LIN28A Is Sufficient for Robust Gamma-Globin Gene and Protein Expression in Adult Erythroblasts.

    Science.gov (United States)

    Lee, Y Terry; de Vasconcellos, Jaira F; Byrnes, Colleen; Kaushal, Megha; Rabel, Antoinette; Tumburu, Laxminath; Allwardt, Joshua M; Miller, Jeffery L

    2015-01-01

    Increasing fetal hemoglobin (HbF) levels in adult humans remains an active area in hematologic research. Here we explored erythroid-specific LIN28A expression for its effect in regulating gamma-globin gene expression and HbF levels in cultured adult erythroblasts. For this purpose, lentiviral transduction vectors were produced with LIN28A expression driven by erythroid-specific gene promoter regions of the human KLF1 or SPTA1 genes. Transgene expression of LIN28A with a linked puromycin resistance marker was restricted to the erythroid lineage as demonstrated by selective survival of erythroid colonies (greater than 95% of all colonies). Erythroblast LIN28A over-expression (LIN28A-OE) did not significantly affect proliferation or inhibit differentiation. Greater than 70% suppression of total let-7 microRNA levels was confirmed in LIN28A-OE cells. Increases in gamma-globin mRNA and protein expression with HbF levels reaching 30-40% were achieved. These data suggest that erythroblast targeting of LIN28A expression is sufficient for increasing fetal hemoglobin expression in adult human erythroblasts.

  7. Non-circadian expression masking clock-driven weak transcription rhythms in U2OS cells.

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    Julia Hoffmann

    Full Text Available U2OS cells harbor a circadian clock but express only a few rhythmic genes in constant conditions. We identified 3040 binding sites of the circadian regulators BMAL1, CLOCK and CRY1 in the U2OS genome. Most binding sites even in promoters do not correlate with detectable rhythmic transcript levels. Luciferase fusions reveal that the circadian clock supports robust but low amplitude transcription rhythms of representative promoters. However, rhythmic transcription of these potentially clock-controlled genes is masked by non-circadian transcription that overwrites the weaker contribution of the clock in constant conditions. Our data suggest that U2OS cells harbor an intrinsically rather weak circadian oscillator. The oscillator has the potential to regulate a large number of genes. The contribution of circadian versus non-circadian transcription is dependent on the metabolic state of the cell and may determine the apparent complexity of the circadian transcriptome.

  8. The human desmin promoter drives robust gene expression for skeletal muscle stem cell-mediated gene therapy.

    Science.gov (United States)

    Jonuschies, Jacqueline; Antoniou, Michael; Waddington, Simon; Boldrin, Luisa; Muntoni, Francesco; Thrasher, Adrian; Morgan, Jennifer

    2014-01-01

    Lentiviral vectors (LVs) represent suitable candidates to mediate gene therapy for muscular dystrophies as they infect dividing and non-dividing cells and integrate their genetic material into the host genome, thereby theoretically mediating longterm expression. We evaluated the ability of LVs where a GFP reporter gene was under the control of five different promoters, to transduce and mediate expression in myogenic and non-myogenic cells in vitro and in skeletal muscle fibres and stem (satellite) cells in vivo. We further analysed lentivirally-transduced satellite cell-derived myoblasts following their transplantation into dystrophic, immunodeficient mouse muscles. The spleen focus-forming virus promoter mediated the highest gene expression in all cell types; the CBX3-HNRPA2B1 ubiquitously-acting chromatin opening element (UCOE) promoter was also active in all cells, whereas the human desmin promoter in isolation or fused with UCOE had lower activity in non-muscle cells. Surprisingly, the human skeletal muscle actin promoter was also active in immune cells. The human desmin promoter mediated robust, persistent reporter gene expression in myogenic cells in vitro, and satellite cells and muscle fibres in vivo. The human desmin promoter combined with UCOE did not significantly increase transgene expression. Therefore, our data indicate that the desmin promoter is suitable for the development of therapeutic purposes.

  9. GAL promoter-driven heterologous gene expression in Saccharomyces cerevisiae Δ strain at anaerobic alcoholic fermentation.

    Science.gov (United States)

    Ahn, Jungoh; Park, Kyung-Min; Lee, Hongweon; Son, Yeo-Jin; Choi, Eui-Sung

    2013-02-01

    The removal of Gal80 protein by gene disruption turned into efficient GAL promoter-driven heterologous gene expression under anaerobic alcoholic fermentation of Saccharomyces cerevisiae. Using lipase B from Candida antarctica as a reporter, the relative strength of GAL10 promoter (P(GAL10) ) in Δgal80 mutant that does not require galactose as an inducer was compared to those of ADH1, PDC1, and PGK promoters, which have been known to work well anaerobically in actively fermenting yeast cells under high glucose concentration. P(GAL10) in the Δgal80 mutant showed 0.8-fold (ADH1), fourfold (PDC1), and 50-fold (PGK) in promoter strength.

  10. Polo-Like Kinase 3 Appears Dispensable for Normal Retinal Development Despite Robust Embryonic Expression.

    Directory of Open Access Journals (Sweden)

    Jillian J Goetz

    Full Text Available During retinogenesis seven different cell types are generated in distinct yet overlapping timepoints from a population of retinal progenitor cells. Previously, we performed single cell transcriptome analyses of retinal progenitor cells to identify candidate genes that may play roles in the generation of early-born retinal neurons. Based on its expression pattern in subsets of early retinal cells, polo-like kinase 3 (Plk3 was identified as one such candidate gene. Further characterization of Plk3 expression by in situ hybridization revealed that this gene is expressed as cells exit the cell cycle. We obtained a Plk3 deficient mouse and investigated changes in the retina's morphology and transcriptome through immunohistochemistry, in situ hybridization and gene expression profiling. These experiments have been performed initially on adult mice and subsequently extended throughout retinal development. Although morphological studies revealed no consistent changes in retinogenesis upon Plk3 loss, microarray profiling revealed potential candidate genes altered in Plk3-KO mice. Further studies will be necessary to understand the connection between these changes in gene expression and the loss of a protein kinase such as Plk3.

  11. Robust control of the seasonal expression of the Arabidopsis FLC gene in a fluctuating environment.

    Science.gov (United States)

    Aikawa, Shinichiro; Kobayashi, Masaki J; Satake, Akiko; Shimizu, Kentaro K; Kudoh, Hiroshi

    2010-06-22

    Plants flower in particular seasons even in natural, fluctuating environments. The molecular basis of temperature-dependent flowering-time regulation has been extensively studied, but little is known about how gene expression is controlled in natural environments. Without a memory of past temperatures, it would be difficult for plants to detect seasons in natural, noisy environments because temperature changes occurring within a few weeks are often inconsistent with seasonal trends. Our 2-y census of the expression of a temperature-dependent flowering-time gene, AhgFLC, in a natural population of perennial Arabidopsis halleri revealed that the regulatory system of this flowering-time gene extracts seasonal cues as if it memorizes temperatures over the past 6 wk. Time-series analysis revealed that as much as 83% of the variation in the AhgFLC expression is explained solely by the temperature for the previous 6 wk, but not by the temperatures over shorter or longer periods. The accuracy of our model in predicting the gene expression pattern under contrasting temperature regimes in the transplant experiments indicates that such modeling incorporating the molecular bases of flowering-time regulation will contribute to predicting plant responses to future climate changes.

  12. Contact call-driven zenk mRNA expression in the brain of the budgerigar (Melopsittacus undulatus).

    Science.gov (United States)

    Brauth, Steven E; Tang, Ye-Zhong; Liang, Wenru; Roberts, Todd F

    2003-09-10

    Contact call-driven zenk (zif268, egr1, NGF1A, Krox 24) mRNA expression was mapped with in situ hybridization histochemistry in a vocal learning parrot, the budgerigar (M. undulatus). Relative to controls, call stimulation induced high zenk mRNA expression in all auditory areas including those closely associated with the vocal system within the anterior forebrain (Brauth et al. (2001) J. Comp. Neurol. 432, 481; (2002) Learn. Memory 9, 76). Thus there is a high correspondence between the distributions of neurons exhibiting contact call-driven zenk protein and mRNA expression in budgerigars. Field L2a, an area reported previously to express only perinucleolar zenk protein localization (Brauth et al. (2002) Learn. Memory 9, 76) also showed zenk mRNA expression.

  13. Absence of caveolin-1 alters heat shock protein expression in spontaneous mammary tumors driven by Her-2/neu expression.

    Science.gov (United States)

    Ciocca, Daniel R; Cuello-Carrión, F Darío; Natoli, Anthony L; Restall, Christina; Anderson, Robin L

    2012-02-01

    In a previous study, we measured caveolin-1 protein levels, both in the normal breast and in breast cancer. The study revealed no association between caveolin-1 expression in the epithelial compartment and clinical disease outcome. However, high levels of caveolin-1 in the stromal tissue surrounding the tumor associated strongly with reduced metastasis and improved survival. Using an animal model, we found that the onset of mammary tumors driven by Her-2/neu expression was accelerated in mice lacking caveolin-1. We have analysed the heat shock protein (Hsp) response in the tumors of mice lacking caveolin-1. In all cases, the mammary tumors were estrogen and progesterone receptor negative, and the levels of Her-2/neu (evaluated by immunohistochemistry) were not different between the caveolin-1 +/+ (n = 8) and the caveolin-1 -/- (n = 7) tumors. However, a significant reduction in the extent of apoptosis was observed in mammary tumors from animals lacking caveolin-1. While Bcl-2, Bax, and survivin levels in the tumors were not different, the amount of HSPA (Hsp70) was almost double in the caveolin-1 -/- tumors. In contrast, HSPB1 (Hsp27/Hsp25) levels were significantly lower in the caveolin-1 -/- tumors. The mammary tumors from caveolin-1 null mice expressed more HSPC4 (gp96 or grp94), but HSPC1 (Hsp90), HSPA5 (grp78), HSPD1 (Hsp60), and CHOP were not altered. No significant changes in these proteins were found in the stroma surrounding these tumors. These results demonstrate that the disruption of the Cav-1 gene can cause alterations of specific Hsps as well as tumor development.

  14. Robust assignment of cancer subtypes from expression data using a uni-variate gene expression average as classifier

    Directory of Open Access Journals (Sweden)

    Ryden Tobias

    2010-10-01

    Full Text Available Abstract Background Genome wide gene expression data is a rich source for the identification of gene signatures suitable for clinical purposes and a number of statistical algorithms have been described for both identification and evaluation of such signatures. Some employed algorithms are fairly complex and hence sensitive to over-fitting whereas others are more simple and straight forward. Here we present a new type of simple algorithm based on ROC analysis and the use of metagenes that we believe will be a good complement to existing algorithms. Results The basis for the proposed approach is the use of metagenes, instead of collections of individual genes, and a feature selection using AUC values obtained by ROC analysis. Each gene in a data set is assigned an AUC value relative to the tumor class under investigation and the genes are ranked according to these values. Metagenes are then formed by calculating the mean expression level for an increasing number of ranked genes, and the metagene expression value that optimally discriminates tumor classes in the training set is used for classification of new samples. The performance of the metagene is then evaluated using LOOCV and balanced accuracies. Conclusions We show that the simple uni-variate gene expression average algorithm performs as well as several alternative algorithms such as discriminant analysis and the more complex approaches such as SVM and neural networks. The R package rocc is freely available at http://cran.r-project.org/web/packages/rocc/index.html.

  15. Robust selectivity for faces in the human amygdala in the absence of expressions.

    Science.gov (United States)

    Mende-Siedlecki, Peter; Verosky, Sara C; Turk-Browne, Nicholas B; Todorov, Alexander

    2013-12-01

    There is a well-established posterior network of cortical regions that plays a central role in face processing and that has been investigated extensively. In contrast, although responsive to faces, the amygdala is not considered a core face-selective region, and its face selectivity has never been a topic of systematic research in human neuroimaging studies. Here, we conducted a large-scale group analysis of fMRI data from 215 participants. We replicated the posterior network observed in prior studies but found equally robust and reliable responses to faces in the amygdala. These responses were detectable in most individual participants, but they were also highly sensitive to the initial statistical threshold and habituated more rapidly than the responses in posterior face-selective regions. A multivariate analysis showed that the pattern of responses to faces across voxels in the amygdala had high reliability over time. Finally, functional connectivity analyses showed stronger coupling between the amygdala and posterior face-selective regions during the perception of faces than during the perception of control visual categories. These findings suggest that the amygdala should be considered a core face-selective region.

  16. Aggressiveness of human melanoma xenograft models is promoted by aneuploidy-driven gene expression deregulation.

    Science.gov (United States)

    Mathieu, Véronique; Pirker, Christine; Schmidt, Wolfgang M; Spiegl-Kreinecker, Sabine; Lötsch, Daniela; Heffeter, Petra; Hegedus, Balazs; Grusch, Michael; Kiss, Robert; Berger, Walter

    2012-04-01

    Melanoma is a devastating skin cancer characterized by distinct biological subtypes. Besides frequent mutations in growth- and survival-promoting genes like BRAF and NRAS, melanomas additionally harbor complex non-random genomic alterations. Using an integrative approach, we have analysed genomic and gene expression changes in human melanoma cell lines (N=32) derived from primary tumors and various metastatic sites and investigated the relation to local growth aggressiveness as xenografts in immuno-compromised mice (N=22). Although the vast majority >90% of melanoma models harbored mutations in either BRAF or NRAS, significant differences in subcutaneous growth aggressiveness became obvious. Unsupervised clustering revealed that genomic alterations rather than gene expression data reflected this aggressive phenotype, while no association with histology, stage or metastatic site of the original melanoma was found. Genomic clustering allowed separation of melanoma models into two subgroups with differing local growth aggressiveness in vivo. Regarding genes expressed at significantly altered levels between these subgroups, a surprising correlation with the respective gene doses (>85% accordance) was found. Genes deregulated at the DNA and mRNA level included well-known cancer genes partly already linked to melanoma (RAS genes, PTEN, AURKA, MAPK inhibitors Sprouty/Spred), but also novel candidates like SIPA1 (a Rap1GAP). Pathway mining further supported deregulation of Rap1 signaling in the aggressive subgroup e.g. by additional repression of two Rap1GEFs. Accordingly, siRNA-mediated down-regulation of SIPA1 exerted significant effects on clonogenicity, adherence and migration in aggressive melanoma models. Together our data suggest that an aneuploidy-driven gene expression deregulation drives local aggressiveness in human melanoma.

  17. Network statistics of genetically-driven gene co-expression modules in mouse crosses

    Directory of Open Access Journals (Sweden)

    Marie-Pier eScott-Boyer

    2013-12-01

    Full Text Available In biology, networks are used in different contexts as ways to represent relationships between entities, such as for instance interactions between genes, proteins or metabolites. Despite progress in the analysis of such networks and their potential to better understand the collective impact of genes on complex traits, one remaining challenge is to establish the biologic validity of gene co-expression networks and to determine what governs their organization. We used WGCNA to construct and analyze seven gene expression datasets from several tissues of mouse recombinant inbred strains (RIS. For six out of the 7 networks, we found that linkage to module QTLs (mQTLs could be established for 29.3% of gene co-expression modules detected in the several mouse RIS. For about 74.6% of such genetically-linked modules, the mQTL was on the same chromosome as the one contributing most genes to the module, with genes originating from that chromosome showing higher connectivity than other genes in the modules. Such modules (that we considered as genetically-driven had network statistic properties (density, centralization and heterogeneity that set them apart from other modules in the network. Altogether, a sizeable portion of gene co-expression modules detected in mouse RIS panels had genetic determinants as their main organizing principle. In addition to providing a biologic interpretation validation for these modules, these genetic determinants imparted on them particular properties that set them apart from other modules in the network, to the point that they can be predicted to a large extent on the basis of their network statistics.

  18. A robust prognostic gene expression signature for early stage lung adenocarcinoma

    DEFF Research Database (Denmark)

    Krzystanek, Marcin; Moldvay, Judit; Szüts, David;

    2016-01-01

    Stage I lung adenocarcinoma is usually not treated with adjuvant chemotherapy; however, around half of these patients do not survive 5 years. Therefore, a reliable prognostic biomarker for early stage patients would be critical to identify those most likely to benefit from early additional treatm...... not given adjuvant therapy. Seven genes consistently obtained statistical significance in Cox regression for overall survival. The combined signature has a weighted mean hazard ratio of 3.2 in all cohorts and 3.0 (C.I. 1.3-7.4, p ...... treatments. Several studies have searched for gene expression prognostic biomarkers for lung adenocarcinoma, but these have not yielded a widely accepted prognosticator. We analyzed gene expression from seven published lung adenocarcinoma cohorts for which we included only stage I and II patients who were...

  19. A robust and efficient method for estimating enzyme complex abundance and metabolic flux from expression data

    OpenAIRE

    Barker, Brandon E.; Sadagopan, Narayanan; Wang, Yiping; Smallbone, Kieran; Myers, Christopher R.; Xi, Hongwei; Locasale, Jason W.; Gu, Zhenglong

    2014-01-01

    A major theme in constraint-based modeling is unifying experimental data, such as biochemical information about the reactions that can occur in a system or the composition and localization of enzyme complexes, with highthroughput data including expression data, metabolomics, or DNA sequencing. The desired result is to increase predictive capability resulting in improved understanding of metabolism. The approach typically employed when only gene (or protein) intensities are available is the cr...

  20. Robust suppression of HIV replication by intracellularly expressed reverse transcriptase aptamers is independent of ribozyme processing.

    Science.gov (United States)

    Lange, Margaret J; Sharma, Tarun K; Whatley, Angela S; Landon, Linda A; Tempesta, Michael A; Johnson, Marc C; Burke, Donald H

    2012-12-01

    RNA aptamers that bind human immunodeficiency virus 1 (HIV-1) reverse transcriptase (RT) also inhibit viral replication, making them attractive as therapeutic candidates and potential tools for dissecting viral pathogenesis. However, it is not well understood how aptamer-expression context and cellular RNA pathways govern aptamer accumulation and net antiviral bioactivity. Using a previously-described expression cassette in which aptamers were flanked by two "minimal core" hammerhead ribozymes, we observed only weak suppression of pseudotyped HIV. To evaluate the importance of the minimal ribozymes, we replaced them with extended, tertiary-stabilized hammerhead ribozymes with enhanced self-cleavage activity, in addition to noncleaving ribozymes with active site mutations. Both the active and inactive versions of the extended hammerhead ribozymes increased inhibition of pseudotyped virus, indicating that processing is not necessary for bioactivity. Clonal stable cell lines expressing aptamers from these modified constructs strongly suppressed infectious virus, and were more effective than minimal ribozymes at high viral multiplicity of infection (MOI). Tertiary stabilization greatly increased aptamer accumulation in viral and subcellular compartments, again regardless of self-cleavage capability. We therefore propose that the increased accumulation is responsible for increased suppression, that the bioactive form of the aptamer is one of the uncleaved or partially cleaved transcripts, and that tertiary stabilization increases transcript stability by reducing exonuclease degradation.

  1. A robust and efficient method for estimating enzyme complex abundance and metabolic flux from expression data.

    Science.gov (United States)

    Barker, Brandon E; Sadagopan, Narayanan; Wang, Yiping; Smallbone, Kieran; Myers, Christopher R; Xi, Hongwei; Locasale, Jason W; Gu, Zhenglong

    2015-12-01

    A major theme in constraint-based modeling is unifying experimental data, such as biochemical information about the reactions that can occur in a system or the composition and localization of enzyme complexes, with high-throughput data including expression data, metabolomics, or DNA sequencing. The desired result is to increase predictive capability and improve our understanding of metabolism. The approach typically employed when only gene (or protein) intensities are available is the creation of tissue-specific models, which reduces the available reactions in an organism model, and does not provide an objective function for the estimation of fluxes. We develop a method, flux assignment with LAD (least absolute deviation) convex objectives and normalization (FALCON), that employs metabolic network reconstructions along with expression data to estimate fluxes. In order to use such a method, accurate measures of enzyme complex abundance are needed, so we first present an algorithm that addresses quantification of complex abundance. Our extensions to prior techniques include the capability to work with large models and significantly improved run-time performance even for smaller models, an improved analysis of enzyme complex formation, the ability to handle large enzyme complex rules that may incorporate multiple isoforms, and either maintained or significantly improved correlation with experimentally measured fluxes. FALCON has been implemented in MATLAB and ATS, and can be downloaded from: https://github.com/bbarker/FALCON. ATS is not required to compile the software, as intermediate C source code is available. FALCON requires use of the COBRA Toolbox, also implemented in MATLAB.

  2. Robust reconstitution of active cell-cycle control complexes from co-expressed proteins in bacteria

    Directory of Open Access Journals (Sweden)

    Harashima Hirofumi

    2012-06-01

    Full Text Available Abstract Background Cell proliferation is an important determinant of plant growth and development. In addition, modulation of cell-division rate is an important mechanism of plant plasticity and is key in adapting of plants to environmental conditions. One of the greatest challenges in understanding the cell cycle of flowering plants is the large families of CDKs and cyclins that have the potential to form many different complexes. However, it is largely unclear which complexes are active. In addition, there are many CDK- and cyclin-related proteins whose biological role is still unclear, i.e. whether they have indeed enzymatic activity. Thus, a biochemical characterization of these proteins is of key importance for the understanding of their function. Results Here we present a straightforward system to systematically express and purify active CDK-cyclin complexes from E. coli extracts. Our method relies on the concomitant production of a CDK activating kinase, which catalyzes the T-loop phosphorylation necessary for kinase activity. Taking the examples of the G1-phase cyclin CYCLIN D3;1 (CYCD3;1, the mitotic cyclin CYCLIN B1;2 (CYCB1;2 and the atypical meiotic cyclin SOLO DANCERS (SDS in conjunction with A-, B1- and B2-type CDKs, we show that different CDKs can interact with various cyclins in vitro but only a few specific complexes have high levels of kinase activity. Conclusions Our work shows that both the cyclin as well as the CDK partner contribute to substrate specificity in plants. These findings refine the interaction networks in cell-cycle control and pinpoint to particular complexes for modulating cell proliferation activity in breeding.

  3. Distinct promoter activation mechanisms modulate noise-driven HIV gene expression

    Science.gov (United States)

    Chavali, Arvind K.; Wong, Victor C.; Miller-Jensen, Kathryn

    2015-12-01

    Latent human immunodeficiency virus (HIV) infections occur when the virus occupies a transcriptionally silent but reversible state, presenting a major obstacle to cure. There is experimental evidence that random fluctuations in gene expression, when coupled to the strong positive feedback encoded by the HIV genetic circuit, act as a ‘molecular switch’ controlling cell fate, i.e., viral replication versus latency. Here, we implemented a stochastic computational modeling approach to explore how different promoter activation mechanisms in the presence of positive feedback would affect noise-driven activation from latency. We modeled the HIV promoter as existing in one, two, or three states that are representative of increasingly complex mechanisms of promoter repression underlying latency. We demonstrate that two-state and three-state models are associated with greater variability in noisy activation behaviors, and we find that Fano factor (defined as variance over mean) proves to be a useful noise metric to compare variability across model structures and parameter values. Finally, we show how three-state promoter models can be used to qualitatively describe complex reactivation phenotypes in response to therapeutic perturbations that we observe experimentally. Ultimately, our analysis suggests that multi-state models more accurately reflect observed heterogeneous reactivation and may be better suited to evaluate how noise affects viral clearance.

  4. Facile promoter deletion in Escherichia coli in response to leaky expression of very robust and benign proteins from common expression vectors

    Directory of Open Access Journals (Sweden)

    Kawe Martin

    2009-01-01

    Full Text Available Abstract Background Overexpression of proteins in Escherichia coli is considered routine today, at least when the protein is soluble and not otherwise toxic for the host. We report here that the massive overproduction of even such "benign" proteins can cause surprisingly efficient promoter deletions in the expression plasmid, leading to the growth of only non-producers, when expression is not well repressed in the newly transformed bacterial cell. Because deletion is so facile, it might impact on high-throughput protein production, e.g. for structural genomics, where not every expression parameter will be monitored. Results We studied the high-level expression of several robust non-toxic proteins using a T5 promoter under lac operator control. Full induction leads to no significant growth retardation. We compared expression from almost identical plasmids with or without the lacI gene together in strains expressing different levels of LacI. Any combination without net overexpression of LacI led to an efficient promoter deletion in the plasmid, although the number of growing colonies and even the plasmid size – all antibiotic-resistant non-producers – was almost normal, and thus the problem not immediately recognizable. However, by assuring sufficient repression during the initial establishment phase of the plasmid, deletion was completely prevented. Conclusion The deletions in the insufficiently repressed system are caused entirely by the burden of high-level translation. Since the E. coli Dps protein, known to protect DNA against stress in the stationary phase, is accumulated in the deletion mutants, the mutation may have taken place during a transient stationary phase. The cause of the deletion is thus distinct from the well known interference of high-level transcription with plasmid replication. The deletion can be entirely prevented by overexpressing LacI, a useful precaution even without any signs of stress caused by the protein.

  5. An empirical likelihood ratio test robust to individual heterogeneity for differential expression analysis of RNA-seq.

    Science.gov (United States)

    Xu, Maoqi; Chen, Liang

    2016-10-21

    The individual sample heterogeneity is one of the biggest obstacles in biomarker identification for complex diseases such as cancers. Current statistical models to identify differentially expressed genes between disease and control groups often overlook the substantial human sample heterogeneity. Meanwhile, traditional nonparametric tests lose detailed data information and sacrifice the analysis power, although they are distribution free and robust to heterogeneity. Here, we propose an empirical likelihood ratio test with a mean-variance relationship constraint (ELTSeq) for the differential expression analysis of RNA sequencing (RNA-seq). As a distribution-free nonparametric model, ELTSeq handles individual heterogeneity by estimating an empirical probability for each observation without making any assumption about read-count distribution. It also incorporates a constraint for the read-count overdispersion, which is widely observed in RNA-seq data. ELTSeq demonstrates a significant improvement over existing methods such as edgeR, DESeq, t-tests, Wilcoxon tests and the classic empirical likelihood-ratio test when handling heterogeneous groups. It will significantly advance the transcriptomics studies of cancers and other complex disease.

  6. ClinData Express – A Metadata Driven Clinical Research Data Management System for Secondary Use of Clinical Data

    OpenAIRE

    Li, Zuofeng; Wen, Jingran; Zhang, Xiaoyan; Wu, Chunxiao; Li, Zuogao; Liu, Lei

    2012-01-01

    Aim to ease the secondary use of clinical data in clinical research, we introduce a metadata driven web-based clinical data management system named ClinData Express. ClinData Express is made up of two parts: 1) m-designer, a standalone software for metadata definition; 2) a web based data warehouse system for data management. With ClinData Express, what the researchers need to do is to define the metadata and data model in the m-designer. The web interface for data collection and specific dat...

  7. Characterization of stem cells and cancer cells on the basis of gene expression profile stability, plasticity, and robustness: dynamical systems theory of gene expressions under cell-cell interaction explains mutational robustness of differentiated cells and suggests how cancer cells emerge.

    Science.gov (United States)

    Kaneko, Kunihiko

    2011-06-01

    Here I present and discuss a model that, among other things, appears able to describe the dynamics of cancer cell origin from the perspective of stable and unstable gene expression profiles. In identifying such aberrant gene expression profiles as lying outside the normal stable states attracted through development and normal cell differentiation, the hypothesis explains why cancer cells accumulate mutations, to which they are not robust, and why these mutations create a new stable state far from the normal gene expression profile space. Such cells are in strong contrast with normal cell types that appeared as an attractor state in the gene expression dynamical system under cell-cell interaction and achieved robustness to noise through evolution, which in turn also conferred robustness to mutation. In complex gene regulation networks, other aberrant cellular states lacking such high robustness are expected to remain, which would correspond to cancer cells.

  8. A simple metric of promoter architecture robustly predicts expression breadth of human genes suggesting that most transcription factors are positive regulators.

    Science.gov (United States)

    Hurst, Laurence D; Sachenkova, Oxana; Daub, Carsten; Forrest, Alistair R R; Huminiecki, Lukasz

    2014-07-31

    Conventional wisdom holds that, owing to the dominance of features such as chromatin level control, the expression of a gene cannot be readily predicted from knowledge of promoter architecture. This is reflected, for example, in a weak or absent correlation between promoter divergence and expression divergence between paralogs. However, an inability to predict may reflect an inability to accurately measure or employment of the wrong parameters. Here we address this issue through integration of two exceptional resources: ENCODE data on transcription factor binding and the FANTOM5 high-resolution expression atlas. Consistent with the notion that in eukaryotes most transcription factors are activating, the number of transcription factors binding a promoter is a strong predictor of expression breadth. In addition, evolutionarily young duplicates have fewer transcription factor binders and narrower expression. Nonetheless, we find several binders and cooperative sets that are disproportionately associated with broad expression, indicating that models more complex than simple correlations should hold more predictive power. Indeed, a machine learning approach improves fit to the data compared with a simple correlation. Machine learning could at best moderately predict tissue of expression of tissue specific genes. We find robust evidence that some expression parameters and paralog expression divergence are strongly predictable with knowledge of transcription factor binding repertoire. While some cooperative complexes can be identified, consistent with the notion that most eukaryotic transcription factors are activating, a simple predictor, the number of binding transcription factors found on a promoter, is a robust predictor of expression breadth.

  9. DREISS: Using State-Space Models to Infer the Dynamics of Gene Expression Driven by External and Internal Regulatory Networks.

    Science.gov (United States)

    Wang, Daifeng; He, Fei; Maslov, Sergei; Gerstein, Mark

    2016-10-01

    Gene expression is controlled by the combinatorial effects of regulatory factors from different biological subsystems such as general transcription factors (TFs), cellular growth factors and microRNAs. A subsystem's gene expression may be controlled by its internal regulatory factors, exclusively, or by external subsystems, or by both. It is thus useful to distinguish the degree to which a subsystem is regulated internally or externally-e.g., how non-conserved, species-specific TFs affect the expression of conserved, cross-species genes during evolution. We developed a computational method (DREISS, dreiss.gerteinlab.org) for analyzing the Dynamics of gene expression driven by Regulatory networks, both External and Internal based on State Space models. Given a subsystem, the "state" and "control" in the model refer to its own (internal) and another subsystem's (external) gene expression levels. The state at a given time is determined by the state and control at a previous time. Because typical time-series data do not have enough samples to fully estimate the model's parameters, DREISS uses dimensionality reduction, and identifies canonical temporal expression trajectories (e.g., degradation, growth and oscillation) representing the regulatory effects emanating from various subsystems. To demonstrate capabilities of DREISS, we study the regulatory effects of evolutionarily conserved vs. divergent TFs across distant species. In particular, we applied DREISS to the time-series gene expression datasets of C. elegans and D. melanogaster during their embryonic development. We analyzed the expression dynamics of the conserved, orthologous genes (orthologs), seeing the degree to which these can be accounted for by orthologous (internal) versus species-specific (external) TFs. We found that between two species, the orthologs have matched, internally driven expression patterns but very different externally driven ones. This is particularly true for genes with evolutionarily

  10. DREISS: Using State-Space Models to Infer the Dynamics of Gene Expression Driven by External and Internal Regulatory Networks

    Science.gov (United States)

    Gerstein, Mark

    2016-01-01

    Gene expression is controlled by the combinatorial effects of regulatory factors from different biological subsystems such as general transcription factors (TFs), cellular growth factors and microRNAs. A subsystem’s gene expression may be controlled by its internal regulatory factors, exclusively, or by external subsystems, or by both. It is thus useful to distinguish the degree to which a subsystem is regulated internally or externally–e.g., how non-conserved, species-specific TFs affect the expression of conserved, cross-species genes during evolution. We developed a computational method (DREISS, dreiss.gerteinlab.org) for analyzing the Dynamics of gene expression driven by Regulatory networks, both External and Internal based on State Space models. Given a subsystem, the “state” and “control” in the model refer to its own (internal) and another subsystem’s (external) gene expression levels. The state at a given time is determined by the state and control at a previous time. Because typical time-series data do not have enough samples to fully estimate the model’s parameters, DREISS uses dimensionality reduction, and identifies canonical temporal expression trajectories (e.g., degradation, growth and oscillation) representing the regulatory effects emanating from various subsystems. To demonstrate capabilities of DREISS, we study the regulatory effects of evolutionarily conserved vs. divergent TFs across distant species. In particular, we applied DREISS to the time-series gene expression datasets of C. elegans and D. melanogaster during their embryonic development. We analyzed the expression dynamics of the conserved, orthologous genes (orthologs), seeing the degree to which these can be accounted for by orthologous (internal) versus species-specific (external) TFs. We found that between two species, the orthologs have matched, internally driven expression patterns but very different externally driven ones. This is particularly true for genes with

  11. GUS Gene Expression Driven by A Citrus Promoter in Transgenic Tobacco and 'Valencia' Sweet Orange

    Science.gov (United States)

    The objective of this work was the transformation of tobacco and ‘Valencia’ sweet orange with the GUS gene driven by the citrus phenylalanine ammonia-lyase (PAL) gene promoter (CsPP). Transformation was accomplished by co-cultivation of tobacco and ‘Valencia’ sweet orange explants with Agrobacteriu...

  12. ClinData Express--a metadata driven clinical research data management system for secondary use of clinical data.

    Science.gov (United States)

    Li, Zuofeng; Wen, Jingran; Zhang, Xiaoyan; Wu, Chunxiao; Li, Zuogao; Liu, Lei

    2012-01-01

    Aim to ease the secondary use of clinical data in clinical research, we introduce a metadata driven web-based clinical data management system named ClinData Express. ClinData Express is made up of two parts: 1) m-designer, a standalone software for metadata definition; 2) a web based data warehouse system for data management. With ClinData Express, what the researchers need to do is to define the metadata and data model in the m-designer. The web interface for data collection and specific database for data storage will be automatically generated. The standards used in the system and the data export modular make sure of the data reuse. The system has been tested on seven disease-data collection in Chinese and one form from dbGap. The flexibility of system makes its great potential usage in clinical research. The system is available at http://code.google.com/p/clindataexpress.

  13. Robustness of s-wave pairing symmetry in iron-based superconductors and its implications for fundamentals of magnetically driven high-temperature superconductivity

    Science.gov (United States)

    Hu, Jiangping; Yuan, Jing

    2016-10-01

    Based on the assumption that the superconducting state belongs to a single irreducible representation of lattice symmetry, we propose that the pairing symmetry in all measured iron-based superconductors is generally consistent with the A 1 g s-wave. Robust s-wave pairing throughout the different families of iron-based superconductors at different doping regions signals two fundamental principles behind high- T c superconducting mechanisms: (i) the correspondence principle: the short-range magnetic-exchange interactions and the Fermi surfaces act collaboratively to achieve high- T c superconductivity and determine pairing symmetries; (ii) the magnetic-selection pairing rule: superconductivity is only induced by the magnetic-exchange couplings from the super-exchange mechanism through cation-anion-cation chemical bonding. These principles explain why unconventional high- T c superconductivity appears to be such a rare but robust phenomena, with its strict requirements regarding the electronic environment. The results will help us to identify new electronic structures that can support high- T c superconductivity.

  14. A novel genetic tool for metabolic optimization of Corynebacterium glutamicum: efficient and repetitive chromosomal integration of synthetic promoter-driven expression libraries

    DEFF Research Database (Denmark)

    Shen, Jing; Chen, Jun; Jensen, Peter Ruhdal

    2017-01-01

    Fine-tuning the expression level of multiple genes is usually pivotal for metabolic optimization. We have developed a tool for this purpose for the important industrial workhorse Corynebacterium glutamicum that allows for the introduction of synthetic promoter-driven expression libraries of arbit......Fine-tuning the expression level of multiple genes is usually pivotal for metabolic optimization. We have developed a tool for this purpose for the important industrial workhorse Corynebacterium glutamicum that allows for the introduction of synthetic promoter-driven expression libraries...

  15. Histone deacetylases regulate gonadotropin-releasing hormone I gene expression via modulating Otx2-driven transcriptional activity.

    Directory of Open Access Journals (Sweden)

    Lu Gan

    Full Text Available BACKGROUND: Precise coordination of the hypothalamic-pituitary-gonadal axis orchestrates the normal reproductive function. As a central regulator, the appropriate synthesis and secretion of gonadotropin-releasing hormone I (GnRH-I from the hypothalamus is essential for the coordination. Recently, emerging evidence indicates that histone deacetylases (HDACs play an important role in maintaining normal reproductive function. In this study, we identify the potential effects of HDACs on Gnrh1 gene transcription. METHODOLOGY/PRINCIPAL FINDINGS: Inhibition of HDACs activities by trichostatin A (TSA and valproic acid (VPA promptly and dramatically repressed transcription of Gnrh1 gene in the mouse immortalized mature GnRH neuronal cells GT1-7. The suppression was connected with a specific region of Gnrh1 gene promoter, which contains two consensus Otx2 binding sites. Otx2 has been known to activate the basal and also enhancer-driven transcription of Gnrh1 gene. The transcriptional activity of Otx2 is negatively modulated by Grg4, a member of the Groucho-related-gene (Grg family. In the present study, the expression of Otx2 was downregulated by TSA and VPA in GT1-7 cells, accompanied with the opposite changes of Grg4 expression. Chromatin immunoprecipitation and electrophoretic mobility shift assays demonstrated that the DNA-binding activity of Otx2 to Gnrh1 gene was suppressed by TSA and VPA. Overexpression of Otx2 partly abolished the TSA- and VPA-induced downregulation of Gnrh1 gene expression. CONCLUSIONS/SIGNIFICANCE: Our data indicate that HDAC inhibitors downregulate Gnrh1 gene expression via repressing Otx2-driven transcriptional activity. This study should provide an insight for our understanding on the effects of HDACs in the reproductive system and suggests that HDACs could be potential novel targets for the therapy of GnRH-related diseases.

  16. LXR driven induction of HDL-cholesterol is independent of intestinal cholesterol absorption and ABCA1 protein expression.

    Science.gov (United States)

    Kannisto, Kristina; Gåfvels, Mats; Jiang, Zhao-Yan; Slätis, Katharina; Hu, Xiaoli; Jorns, Carl; Steffensen, Knut R; Eggertsen, Gösta

    2014-01-01

    We investigated whether: (1) liver X receptor (LXR)-driven induction of high-density lipoprotein cholesterol (HDL-C) and other LXR-mediated effects on cholesterol metabolism depend on intestinal cholesterol absorption; and (2) combined treatment with the LXR agonist GW3965 and the cholesterol absorption inhibitor ezetimibe results in synergistic effects on cholesterol metabolism that could be beneficial for treatment of atherosclerosis. Mice were fed 0.2 % cholesterol and treated with GW3965+ezetimibe, GW3965 or ezetimibe. GW3965+ezetimibe treatment elevated serum HDL-C and Apolipoprotein (Apo) AI, effectively reduced the intestinal cholesterol absorption and increased the excretion of faecal neutral sterols. No changes in intestinal ATP-binding cassette (ABC) A1 or ABCG5 protein expression were observed, despite increased mRNA expression, while hepatic ABCA1 was slightly reduced. The combined treatment caused a pronounced down-regulation of intestinal Niemann-Pick C1-like 1 (NPC1L1) and reduced hepatic and intestinal cholesterol levels. GW3965 did not affect the intestinal cholesterol absorption, but increased serum HDL-C and ApoAI levels. GW3965 also increased Apoa1 mRNA levels in primary mouse hepatocytes and HEPA1-6 cells. Ezetimibe reduced the intestinal cholesterol absorption, ABCA1 and ABCG5, but did not affect the serum HDL-C or ApoAI levels. Thus, the LXR-driven induction of HDL-C and ApoAI was independent of the intestinal cholesterol absorption and increased expression of intestinal or hepatic ABCA1 was not required. Inhibited influx of cholesterol via NPC1L1 and/or low levels of intracellular cholesterol prevented post-transcriptional expression of intestinal ABCA1 and ABCG5, despite increased mRNA levels. Combined LXR activation and blocked intestinal cholesterol absorption induced effective faecal elimination of cholesterol.

  17. Establishment of a robust hepatitis C virus replicon cell line over-expressing P-glycoprotein that facilitates analysis of P-gp drug transporter effects on inhibitor antiviral activity.

    Science.gov (United States)

    Hernandez, Dennis; Falk, Paul; Yu, Fei; Zhai, Guangzhi; Quan, Yong; Faria, Teresa; Cao, Kai; Scola, Paul; McPhee, Fiona

    2013-01-01

    P-glycoprotein (P-gp) is an active efflux pump affecting the pharmacokinetic (PK) profiles of drugs that are P-gp substrates. The Caco-2 bi-directional assay is widely used to identify drug-P-gp interactions in vitro. For molecules exhibiting non-classical drug properties however, ambiguous results limit its use in lead optimization. The goal of this study was to develop a robust cell-based assay system to directly measure the role of P-gp-driven efflux in reducing the potency of hepatitis C virus (HCV) replication inhibitors. Vinblastine (Vin) was employed to select for a Vin-resistant HCV replicon (313-11) from the parental cell line (377-2). The 313-11 cell line was >50-fold resistant to Vin and over-expressed P-gp, as determined by Western immunoblots. Increased expression of P-gp was mediated by up-regulation of the MDR1 transcript. The reduced potency of different classes of HCV replication inhibitors in the 313-11 P-gp cell line was restored in the presence of known P-gp inhibitors. Addition of the P-gp inhibitor, tariquidar, increased the uptake of a radiolabeled HCV replication inhibitor by 14-fold in the 313-11 replicon cell line. Finally, a positive correlation was demonstrated between potency in the 313-11 replicon and the bi-directional Caco-2 efflux ratio for a panel of HCV protease inhibitors. In conclusion, a robust P-gp HCV replicon cell-based assay has been developed to measure the effect of the P-gp efflux pump on the potency of different classes of HCV replication inhibitors. This system establishes a direct correlation between antiviral activity and the effect of P-gp efflux in a single cell line.

  18. Long term expression of bicistronic vector driven by the FGF-1 IRES in mouse muscle

    Directory of Open Access Journals (Sweden)

    Van den Berghe Loïc

    2007-10-01

    Full Text Available Abstract Background Electrotransfer of plasmid DNA into skeletal muscle is a promising strategy for the delivery of therapeutic molecules targeting various muscular diseases, cancer and lower-limb ischemia. Internal Ribosome Entry Sites (IRESs allow co-expression of proteins of interest from a single transcriptional unit. IRESs are RNA elements that have been found in viral RNAs as well as a variety of cellular mRNAs with long 5' untranslated regions. While the encephalomyocarditis virus (EMCV IRES is often used in expression vectors, we have shown that the FGF-1 IRES is equally active to drive short term transgene expression in mouse muscle. To compare the ability of the FGF-1 IRES to drive long term expression against the EMCV and FGF-2 IRESs, we performed analyses of expression kinetics using bicistronic vectors that express the bioluminescent renilla and firefly luciferase reporter genes. Long term expression of bicistronic vectors was also compared to that of monocistronic vectors. Bioluminescence was quantified ex vivo using a luminometer and in vivo using a CCD camera that monitors luminescence within live animals. Results Our data demonstrate that the efficiency of the FGF-1 IRES is comparable to that of the EMCV IRES for long term expression of bicistronic transgenes in mouse muscle, whereas the FGF-2 IRES has a very poor activity. Interestingly, we show that despite the global decrease of vector expression over time, the ratio of firefly to renilla luciferase remains stable with bicistronic vectors containing the FGF-1 or FGF-2 IRES and is slightly affected with the EMCV IRES, whereas it is clearly unstable for mixed monocistronic vectors. In addition, long term expression more drastically decreases with monocistronic vectors, and is different for single or mixed vector injection. Conclusion These data validate the use of bicistronic vectors rather than mixed monocistronic vectors for long term expression, and support the use of the

  19. TMPRSS2- driven ERG expression in vivo increases self-renewal and maintains expression in a castration resistant subpopulation.

    Directory of Open Access Journals (Sweden)

    Orla M Casey

    Full Text Available Genomic rearrangements commonly occur in many types of cancers and often initiate or alter the progression of disease. Here we describe an in vivo mouse model that recapitulates the most frequent rearrangement in prostate cancer, the fusion of the promoter region of TMPRSS2 with the coding region of the transcription factor, ERG. A recombinant bacterial artificial chromosome including an extended TMPRSS2 promoter driving genomic ERG was constructed and used for transgenesis in mice. TMPRSS2-ERG expression was evaluated in tissue sections and FACS-fractionated prostate cell populations. In addition to the anticipated expression in luminal cells, TMPRSS2-ERG was similarly expressed in the Sca-1(hi/EpCAM(+ basal/progenitor fraction, where expanded numbers of clonogenic self-renewing progenitors were found, as assayed by in vitro sphere formation. These clonogenic cells increased intrinsic self renewal in subsequent generations. In addition, ERG dependent self-renewal and invasion in vitro was demonstrated in prostate cell lines derived from the model. Clinical studies have suggested that the TMPRSS2-ERG translocation occurs early in prostate cancer development. In the model described here, the presence of the TMPRSS2-ERG fusion alone was not transforming but synergized with heterozygous Pten deletion to promote PIN. Taken together, these data suggest that one function of TMPRSS2-ERG is the expansion of self-renewing cells, which may serve as targets for subsequent mutations. Primary prostate epithelial cells demonstrated increased post transcriptional turnover of ERG compared to the TMPRSS2-ERG positive VCaP cell line, originally isolated from a prostate cancer metastasis. Finally, we determined that TMPRSS2-ERG expression occurred in both castration-sensitive and resistant prostate epithelial subpopulations, suggesting the existence of androgen-independent mechanisms of TMPRSS2 expression in prostate epithelium.

  20. A Hybrid One-Way ANOVA Approach for the Robust and Efficient Estimation of Differential Gene Expression with Multiple Patterns

    OpenAIRE

    Mohammad Manir Hossain Mollah; Rahman Jamal; Norfilza Mohd Mokhtar; Roslan Harun; Md. Nurul Haque Mollah

    2015-01-01

    Background Identifying genes that are differentially expressed (DE) between two or more conditions with multiple patterns of expression is one of the primary objectives of gene expression data analysis. Several statistical approaches, including one-way analysis of variance (ANOVA), are used to identify DE genes. However, most of these methods provide misleading results for two or more conditions with multiple patterns of expression in the presence of outlying genes. In this paper, an attempt ...

  1. The Receptive-Expressive Gap in the Vocabulary of Young Second-Language Learners: Robustness and Possible Mechanisms

    Science.gov (United States)

    Gibson, Todd A.; Oller, D. Kimbrough; Jarmulowicz, Linda; Ethington, Corinna A.

    2012-01-01

    Adults and children learning a second language show difficulty accessing expressive vocabulary that appears accessible receptively in their first language (L1). We call this discrepancy the receptive-expressive gap. Kindergarten Spanish (L1)-English (L2) sequential bilinguals were given standardized tests of receptive and expressive vocabulary in…

  2. GOexpress: an R/Bioconductor package for the identification and visualisation of robust gene ontology signatures through supervised learning of gene expression data.

    Science.gov (United States)

    Rue-Albrecht, Kévin; McGettigan, Paul A; Hernández, Belinda; Nalpas, Nicolas C; Magee, David A; Parnell, Andrew C; Gordon, Stephen V; MacHugh, David E

    2016-03-11

    Identification of gene expression profiles that differentiate experimental groups is critical for discovery and analysis of key molecular pathways and also for selection of robust diagnostic or prognostic biomarkers. While integration of differential expression statistics has been used to refine gene set enrichment analyses, such approaches are typically limited to single gene lists resulting from simple two-group comparisons or time-series analyses. In contrast, functional class scoring and machine learning approaches provide powerful alternative methods to leverage molecular measurements for pathway analyses, and to compare continuous and multi-level categorical factors. We introduce GOexpress, a software package for scoring and summarising the capacity of gene ontology features to simultaneously classify samples from multiple experimental groups. GOexpress integrates normalised gene expression data (e.g., from microarray and RNA-seq experiments) and phenotypic information of individual samples with gene ontology annotations to derive a ranking of genes and gene ontology terms using a supervised learning approach. The default random forest algorithm allows interactions between all experimental factors, and competitive scoring of expressed genes to evaluate their relative importance in classifying predefined groups of samples. GOexpress enables rapid identification and visualisation of ontology-related gene panels that robustly classify groups of samples and supports both categorical (e.g., infection status, treatment) and continuous (e.g., time-series, drug concentrations) experimental factors. The use of standard Bioconductor extension packages and publicly available gene ontology annotations facilitates straightforward integration of GOexpress within existing computational biology pipelines.

  3. Keratin-6 driven ODC expression to hair follicle keratinocytes enhances stemness and tumorigenesis by negatively regulating Notch

    Energy Technology Data Exchange (ETDEWEB)

    Arumugam, Aadithya; Weng, Zhiping; Chaudhary, Sandeep C.; Afaq, Farrukh [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019 (United States); Elmets, Craig A. [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019 (United States); Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019 (United States); Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)

    2014-08-29

    Highlights: • Targeting ODC to hair follicle augments skin carcinogenesis and invasive SCCs. • Hair follicle ODC expands stem cell compartment carrying CD34{sup +}/K15{sup +}/p63{sup +} keratinocytes. • Negatively regulated Notch1 is associated with expansion of stem cell compartment. - Abstract: Over-expression of ornithine decarboxylase (ODC) is known to be involved in the epidermal carcinogenesis. However, the mechanism by which it enhances skin carcinogenesis remains undefined. Recently, role of stem cells localized in various epidermal compartments has been shown in the pathogenesis of skin cancer. To direct ODC expression in distinct epidermal compartments, we have developed keratin 6 (K6)-ODC/SKH-1 and keratin 14 (K14)-ODC/SKH-1 mice and employed them to investigate the role of ODC directed to these epidermal compartments on UVB-induced carcinogenesis. K6-driven ODC over-expression directed to outer root sheath (ORS) of hair follicle was more effective in augmenting tumorigenesis as compared to mice where K14-driven ODC expression was directed to inter-follicular epidermal keratinocytes. Chronically UVB-irradiated K6-ODC/SKH-1 developed 15 ± 2.5 tumors/mouse whereas K14-ODC/SKH-1 developed only 6.8 ± 1.5 tumors/mouse. K6-ODC/SKH-1 showed augmented UVB-induced proliferation and much higher pro-inflammatory responses than K14-ODC/SKH-1 mice. Tumors induced in K6-ODC/SKH-1 were rapidly growing, invasive and ulcerative squamous cell carcinoma (SCC) showing decreased expression of epidermal polarity marker E-cadherin and enhanced mesenchymal marker, fibronectin. Interestingly, the number of CD34/CK15/p63 positive stem-like cells was significantly higher in chronically UVB-irradiated K6-ODC/SKH-1 as compared to K14-ODC/SKH-1 mice. Reduced Notch1 expression was correlated with the expansion of stem cell compartment in these animals. However, other signaling pathways such as DNA damage response or mTOR signaling pathways were not significantly different in

  4. Extended Closed-form Expressions for the Robust Symmetrical Number System Dynamic Range and an Efficient Algorithm for its Computation

    Science.gov (United States)

    2014-01-01

    afloat as a surface warfare officer trained in naval nuclear propulsion, including Assistant Reactor Officer on USS ENTERPRISE (CVN-65) and Chief Staff...integer sequences, were formulated based on coprime modular systems. Symmetrical number systems include the symmetrical number system (SNS), the optimum...real number x we write log x for the maximum between 2 and the natural logarithm of x. II. ROBUST SYMMETRICAL NUMBER SYSTEM The RSNS is a modular based

  5. Aquaporin 5 Expression in Mouse Mammary Gland Cells Is Not Driven by Promoter Methylation

    Directory of Open Access Journals (Sweden)

    Barbara Arbeithuber

    2015-01-01

    Full Text Available Several studies have revealed that aquaporins play a role in tumor progression and invasion. In breast carcinomas, high levels of aquaporin 5 (AQP5, a membrane protein involved in water transport, have been linked to increased cell proliferation and migration, thus facilitating tumor progression. Despite the potential role of AQP5 in mammary oncogenesis, the mechanisms controlling mammary AQP5 expression are poorly understood. In other tissues, AQP5 expression has been correlated with its promoter methylation, yet, very little is known about AQP5 promoter methylation in the mammary gland. In this work, we used the mouse mammary gland cell line EpH4, in which we controlled AQP5 expression via the steroid hormone dexamethasone (Dex to further investigate mechanisms regulating AQP5 expression. In this system, we observed a rapid drop of AQP5 mRNA levels with a delay of several hours in AQP5 protein, suggesting transcriptional control of AQP5 levels. Yet, AQP5 expression was independent of its promoter methylation, or to the presence of negative glucocorticoid receptor elements (nGREs in its imminent promoter region, but was rather influenced by the cell proliferative state or cell density. We conclude that AQP5 promoter methylation is not a universal mechanism for AQP5 regulation and varies on cell and tissue type.

  6. Real-time speech-driven animation of expressive talking faces

    Science.gov (United States)

    Liu, Jia; You, Mingyu; Chen, Chun; Song, Mingli

    2011-05-01

    In this paper, we present a real-time facial animation system in which speech drives mouth movements and facial expressions synchronously. Considering five basic emotions, a hierarchical structure with an upper layer of emotion classification is established. Based on the recognized emotion label, the under-layer classification at sub-phonemic level has been modelled on the relationship between acoustic features of frames and audio labels in phonemes. Using certain constraint, the predicted emotion labels of speech are adjusted to gain the facial expression labels which are combined with sub-phonemic labels. The combinations are mapped into facial action units (FAUs), and audio-visual synchronized animation with mouth movements and facial expressions is generated by morphing between FAUs. The experimental results demonstrate that the two-layer structure succeeds in both emotion and sub-phonemic classifications, and the synthesized facial sequences reach a comparative convincing quality.

  7. Kita driven expression of oncogenic HRAS leads to early onset and highly penetrant melanoma in zebrafish.

    Directory of Open Access Journals (Sweden)

    Cristina Santoriello

    Full Text Available BACKGROUND: Melanoma is the most aggressive and lethal form of skin cancer. Because of the increasing incidence and high lethality of melanoma, animal models for continuously observing melanoma formation and progression as well as for testing pharmacological agents are needed. METHODOLOGY AND PRINCIPAL FINDINGS: Using the combinatorial Gal4-UAS system, we have developed a zebrafish transgenic line that expresses oncogenic HRAS under the kita promoter. Already at 3 days transgenic kita-GFP-RAS larvae show a hyper-pigmentation phenotype as earliest evidence of abnormal melanocyte growth. By 2-4 weeks, masses of transformed melanocytes form in the tail stalk of the majority of kita-GFP-RAS transgenic fish. The adult tumors evident between 1-3 months of age faithfully reproduce the immunological, histological and molecular phenotypes of human melanoma, but on a condensed time-line. Furthermore, they show transplantability, dependence on mitfa expression and do not require additional mutations in tumor suppressors. In contrast to kita expressing melanocyte progenitors that efficiently develop melanoma, mitfa expressing progenitors in a second Gal4-driver line were 4 times less efficient in developing melanoma during the three months observation period. CONCLUSIONS AND SIGNIFICANCE: This indicates that zebrafish kita promoter is a powerful tool for driving oncogene expression in the right cells and at the right level to induce early onset melanoma in the presence of tumor suppressors. Thus our zebrafish model provides a link between kita expressing melanocyte progenitors and melanoma and offers the advantage of a larval phenotype suitable for large scale drug and genetic modifier screens.

  8. (Im)Perfect robustness and adaptation of metabolic networks subject to metabolic and gene-expression regulation: marrying control engineering with metabolic control analysis.

    Science.gov (United States)

    He, Fei; Fromion, Vincent; Westerhoff, Hans V

    2013-11-21

    Metabolic control analysis (MCA) and supply-demand theory have led to appreciable understanding of the systems properties of metabolic networks that are subject exclusively to metabolic regulation. Supply-demand theory has not yet considered gene-expression regulation explicitly whilst a variant of MCA, i.e. Hierarchical Control Analysis (HCA), has done so. Existing analyses based on control engineering approaches have not been very explicit about whether metabolic or gene-expression regulation would be involved, but designed different ways in which regulation could be organized, with the potential of causing adaptation to be perfect. This study integrates control engineering and classical MCA augmented with supply-demand theory and HCA. Because gene-expression regulation involves time integration, it is identified as a natural instantiation of the 'integral control' (or near integral control) known in control engineering. This study then focuses on robustness against and adaptation to perturbations of process activities in the network, which could result from environmental perturbations, mutations or slow noise. It is shown however that this type of 'integral control' should rarely be expected to lead to the 'perfect adaptation': although the gene-expression regulation increases the robustness of important metabolite concentrations, it rarely makes them infinitely robust. For perfect adaptation to occur, the protein degradation reactions should be zero order in the concentration of the protein, which may be rare biologically for cells growing steadily. A proposed new framework integrating the methodologies of control engineering and metabolic and hierarchical control analysis, improves the understanding of biological systems that are regulated both metabolically and by gene expression. In particular, the new approach enables one to address the issue whether the intracellular biochemical networks that have been and are being identified by genomics and systems

  9. HDAC5 controls MEF2C-driven sclerostin expression in osteocytes.

    Science.gov (United States)

    Wein, Marc N; Spatz, Jordan; Nishimori, Shigeki; Doench, John; Root, David; Babij, Philip; Nagano, Kenichi; Baron, Roland; Brooks, Daniel; Bouxsein, Mary; Pajevic, Paola Divieti; Kronenberg, Henry M

    2015-03-01

    Osteocytes secrete paracrine factors that regulate the balance between bone formation and destruction. Among these molecules, sclerostin (encoded by the gene SOST) inhibits osteoblastic bone formation and is an osteoporosis drug target. The molecular mechanisms underlying SOST expression remain largely unexplored. Here, we report that histone deacetylase 5 (HDAC5) negatively regulates sclerostin levels in osteocytes in vitro and in vivo. HDAC5 shRNA increases, whereas HDAC5 overexpression decreases SOST expression in the novel murine Ocy454 osteocytic cell line. HDAC5 knockout mice show increased levels of SOST mRNA, more sclerostin-positive osteocytes, decreased Wnt activity, low trabecular bone density, and reduced bone formation by osteoblasts. In osteocytes, HDAC5 binds and inhibits the function of MEF2C, a crucial transcription factor for SOST expression. Using chromatin immunoprecipitation, we have mapped endogenous MEF2C binding in the SOST gene to a distal intergenic enhancer 45 kB downstream from the transcription start site. HDAC5 deficiency increases SOST enhancer MEF2C chromatin association and H3K27 acetylation and decreases recruitment of corepressors NCoR and HDAC3. HDAC5 associates with and regulates the transcriptional activity of this enhancer, suggesting direct regulation of SOST gene expression by HDAC5 in osteocytes. Finally, increased sclerostin production achieved by HDAC5 shRNA is abrogated by simultaneous knockdown of MEF2C, indicating that MEF2C is a major target of HDAC5 in osteocytes.

  10. Dmp1 Promoter-Driven Diphtheria Toxin Receptor Transgene Expression Directs Unforeseen Effects in Multiple Tissues

    Directory of Open Access Journals (Sweden)

    Ahmed Al-Jazzar

    2016-12-01

    Full Text Available Mice harbouring a dentin matrix protein 1 (Dmp1 promoter-driven human diphtheria toxin (DT receptor (HDTR transgene (Tg have recently been used to attain targeted ablation of osteocytes by diphtheria toxin (DT treatment in order to define osteocyte function. Use of these Tg mice has asserted mechano- and novel paracrine regulatory osteocyte functions. To explore osteocyte roles fully, we sought to confirm the selectivity of DT effects in these transgenic mice. However, our findings revealed incomplete DT-induced osteocyte ablation, prevalent HDTR misexpression, as well as more prominent histopathological DT-induced changes in multiple organs in Tg than in wild-type (WT littermate mice. Mechanistic evidence for DT action, via prominent regulation of phosphorylation status of elongation factor-2 (EF-2, was also found in many non-skeletal tissues in Tg mice; indicative of direct “off-target” DT action. Finally, very rapid deterioration in health and welfare status in response to DT treatment was observed in these Tg when compared to WT control mice. Together, these data lead us to conclude that alternative models for osteocyte ablation should be sought and caution be exercised when drawing conclusions from experiments using these Tg mice alone.

  11. Aggressiveness of human melanoma xenograft models is promoted by aneuploidy-driven gene expression deregulation

    OpenAIRE

    Mathieu, Véronique; Pirker, Christine; Schmidt, Wolfgang M.; Spiegl-Kreinecker, Sabine; Lötsch, Daniela; Heffeter, Petra; Hegedus, Balazs; Grusch, Michael; Kiss, Robert; Berger, Walter

    2012-01-01

    Melanoma is a devastating skin cancer characterized by distinct biological subtypes. Besides frequent mutations in growth- and survival-promoting genes like BRAF and NRAS, melanomas additionally harbor complex non-random genomic alterations. Using an integrative approach, we have analysed genomic and gene expression changes in human melanoma cell lines (N=32) derived from primary tumors and various metastatic sites and investigated the relation to local growth aggressiveness as xenografts in ...

  12. Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis.

    Directory of Open Access Journals (Sweden)

    John T Pesce

    2009-04-01

    Full Text Available Macrophage-specific expression of Arginase-1 is commonly believed to promote inflammation, fibrosis, and wound healing by enhancing L-proline, polyamine, and Th2 cytokine production. Here, however, we show that macrophage-specific Arg1 functions as an inhibitor of inflammation and fibrosis following infection with the Th2-inducing pathogen Schistosoma mansoni. Although susceptibility to infection was not affected by the conditional deletion of Arg1 in macrophages, Arg1(-/flox;LysMcre mice died at an accelerated rate. The mortality was not due to acute Th1/NOS2-mediated hepatotoxicity or endotoxemia. Instead, granulomatous inflammation, liver fibrosis, and portal hypertension increased in infected Arg1(-/flox;LysMcre mice. Similar findings were obtained with Arg1(flox/flox;Tie2cre mice, which delete Arg1 in all macrophage populations. Production of Th2 cytokines increased in the infected Arg1(-/flox;LysMcre mice, and unlike alternatively activated wild-type macrophages, Arg1(-/flox;LysMcre macrophages failed to inhibit T cell proliferation in vitro, providing an underlying mechanism for the exacerbated Th2 pathology. The suppressive activity of Arg1-expressing macrophages was independent of IL-10 and TGF-beta1. However, when exogenous L-arginine was provided, T cell proliferation was restored, suggesting that Arg1-expressing macrophages deplete arginine, which is required to sustain CD4(+ T cell responses. These data identify Arg1 as the essential suppressive mediator of alternatively activated macrophages (AAM and demonstrate that Arg1-expressing macrophages function as suppressors rather than inducers of Th2-dependent inflammation and fibrosis.

  13. Heterologous gene expression driven by carbonic anhydrase gene promoter in Dunaliella salina

    Institute of Scientific and Technical Information of China (English)

    CHAI Yurong; LU Yumin; WANG Tianyun; HOU Weihong; XUE Lexun

    2006-01-01

    Dunaliella salina, a halotolerant unicellular green alga without a rigid cell wall, can live in salinities ranging from 0.05 to 5 mol/L NaCl. These features of D. salina make it an ideal host for the production of antibodies, oral vaccine, and commercially valuable polypeptides. To produce high level of heterologous proteins from D. salina, highly efficientpromoters are required to drive expression of target genes under controlled condition. In the present study, we cloned a 5' franking region of 1.4 kb from the carbonic anhydrase (CAH) gene of D. salina by genomic walking and PCR. The fragment was ligated to the pMD18-T vector and characterized. Sequence analysis indicated that this region contained conserved motifs, including a TATA- like box and CAAT-box. Tandem (GT)n repeats that had a potential role of transcriptional control, were also found in this region. The transcription start site (TSS) of the CAH gene was determined by 5' RACE and nested PCR method. Transformation assays showed that the 1.4 kb fragment was able to drive expression of the selectable bar (bialaphos resistance) gene when the fusion was transformed into D. salina by biolistics.Northern blotting hybridizations showed that the bar transcript was most abundant in cells grown in 2 mol/L NaCl, and less abundant in 0.5 mol/L NaCl, indicating that expression of the bar gene was induced at high salinity. These results suggest the potential use of the CAH gene promoter to induce the expression of heterologous genes in D. salina under varied salt condition.

  14. Stroke-associated pattern of gene expression previously identified by machine-learning is diagnostically robust in an independent patient population.

    Science.gov (United States)

    O'Connell, Grant C; Chantler, Paul D; Barr, Taura L

    2017-12-01

    Our group recently employed genome-wide transcriptional profiling in tandem with machine-learning based analysis to identify a ten-gene pattern of differential expression in peripheral blood which may have utility for detection of stroke. The objective of this study was to assess the diagnostic capacity and temporal stability of this stroke-associated transcriptional signature in an independent patient population. Publicly available whole blood microarray data generated from 23 ischemic stroke patients at 3, 5, and 24 h post-symptom onset, as well from 23 cardiovascular disease controls, were obtained via the National Center for Biotechnology Information Gene Expression Omnibus. Expression levels of the ten candidate genes (ANTXR2, STK3, PDK4, CD163, MAL, GRAP, ID3, CTSZ, KIF1B, and PLXDC2) were extracted, compared between groups, and evaluated for their discriminatory ability at each time point. We observed a largely identical pattern of differential expression between stroke patients and controls across the ten candidate genes as reported in our prior work. Furthermore, the coordinate expression levels of the ten candidate genes were able to discriminate between stroke patients and controls with levels of sensitivity and specificity upwards of 90% across all three time points. These findings confirm the diagnostic robustness of the previously identified pattern of differential expression in an independent patient population, and further suggest that it is temporally stable over the first 24 h of stroke pathology.

  15. microRNA as a potential vector for the propagation of robustness in protein expression and oscillatory dynamics within a ceRNA network.

    Directory of Open Access Journals (Sweden)

    Claude Gérard

    Full Text Available microRNAs (miRNAs are small noncoding RNAs that are important post-transcriptional regulators of gene expression. miRNAs can induce thresholds in protein synthesis. Such thresholds in protein output can be also achieved by oligomerization of transcription factors (TF for the control of gene expression. First, we propose a minimal model for protein expression regulated by miRNA and by oligomerization of TF. We show that miRNA and oligomerization of TF generate a buffer, which increases the robustness of protein output towards molecular noise as well as towards random variation of kinetics parameters. Next, we extend the model by considering that the same miRNA can bind to multiple messenger RNAs, which accounts for the dynamics of a minimal competing endogenous RNAs (ceRNAs network. The model shows that, through common miRNA regulation, TF can control the expression of all proteins formed by the ceRNA network, even if it drives the expression of only one gene in the network. The model further suggests that the threshold in protein synthesis mediated by the oligomerization of TF can be propagated to the other genes, which can increase the robustness of the expression of all genes in such ceRNA network. Furthermore, we show that a miRNA could increase the time delay of a "Goodwin-like" oscillator model, which may favor the occurrence of oscillations of large amplitude. This result predicts important roles of miRNAs in the control of the molecular mechanisms leading to the emergence of biological rhythms. Moreover, a model for the latter oscillator embedded in a ceRNA network indicates that the oscillatory behavior can be propagated, via the shared miRNA, to all proteins formed by such ceRNA network. Thus, by means of computational models, we show that miRNAs could act as vectors allowing the propagation of robustness in protein synthesis as well as oscillatory behaviors within ceRNA networks.

  16. Multicistronic lentiviral vectors containing the FMDV 2A cleavage factor demonstrate robust expression of encoded genes at limiting MOI

    Directory of Open Access Journals (Sweden)

    Margison Geoffrey P

    2006-03-01

    Full Text Available Abstract Background A number of gene therapy applications would benefit from vectors capable of expressing multiple genes. In this study we explored the feasibility and efficiency of expressing two or three transgenes in HIV-1 based lentiviral vector. Bicistronic and tricistronic self-inactivating lentiviral vectors were constructed employing the internal ribosomal entry site (IRES sequence of encephalomyocarditis virus (EMCV and/or foot-and-mouth disease virus (FMDV cleavage factor 2A. We employed enhanced green fluorescent protein (eGFP, O6-methylguanine-DNA-methyltransferase (MGMT, and homeobox transcription factor HOXB4 as model genes and their expression was detected by appropriate methods including fluorescence microscopy, flow cytometry, immunocytochemistry, biochemical assay, and western blotting. Results All the multigene vectors produced high titer virus and were able to simultaneously express two or three transgenes in transduced cells. However, the level of expression of individual transgenes varied depending on: the transgene itself; its position within the construct; the total number of transgenes expressed; the strategy used for multigene expression and the average copy number of pro-viral insertions. Notably, at limiting MOI, the expression of eGFP in a bicistronic vector based on 2A was ~4 times greater than that of an IRES based vector. Conclusion The small and efficient 2A sequence can be used alone or in combination with an IRES for the construction of multicistronic lentiviral vectors which can express encoded transgenes at functionally relevant levels in cells containing an average of one pro-viral insert.

  17. Hepatitis C Virus Driven AXL Expression Suppresses the Hepatic Type I Interferon Response.

    Directory of Open Access Journals (Sweden)

    Scott A Read

    Full Text Available Treatment of chronic hepatitis C virus (HCV infection is evolving rapidly with the development of novel direct acting antivirals (DAAs, however viral clearance remains intimately linked to the hepatic innate immune system. Patients demonstrating a high baseline activation of interferon stimulated genes (ISGs, termed interferon refractoriness, are less likely to mount a strong antiviral response and achieve viral clearance when placed on treatment. As a result, suppressor of cytokine signalling (SOCS 3 and other regulators of the IFN response have been identified as key candidates for the IFN refractory phenotype due to their regulatory role on the IFN response. AXL is a receptor tyrosine kinase that has been identified as a key regulator of interferon (IFN signalling in myeloid cells of the immune system, but has not been examined in the context of chronic HCV infection. Here, we show that AXL is up-regulated following HCV infection, both in vitro and in vivo and is likely induced by type I/III IFNs and inflammatory signalling pathways. AXL inhibited type IFNα mediated ISG expression resulting in a decrease in its antiviral efficacy against HCV in vitro. Furthermore, patients possessing the favourable IFNL3 rs12979860 genotype associated with treatment response, showed lower AXL expression in the liver and a stronger induction of AXL in the blood, following their first dose of IFN. Together, these data suggest that elevated AXL expression in the liver may mediate an IFN-refractory phenotype characteristic of patients possessing the unfavourable rs12979860 genotype, which is associated with lower rates of viral clearance.

  18. Nutritionally driven differential gene expression leads to heterochronic brain development in honeybee castes.

    Directory of Open Access Journals (Sweden)

    Lívia Maria Moda

    Full Text Available The differential feeding regimes experienced by the queen and worker larvae of the honeybee Apis mellifera shape a complex endocrine response cascade that ultimately gives rise to differences in brain morphologies. Brain development analyzed at the morphological level from the third (L3 through fifth (L5 larval instars revealed an asynchrony between queens and workers. In the feeding phase of the last larval instar (L5F, two well-formed structures, pedunculi and calyces, are identifiable in the mushroom bodies of queens, both of which are not present in workers until a later phase (spinning phase, L5S. Genome-wide expression analyses and normalized transcript expression experiments monitoring specific genes revealed that this differential brain development starts earlier, during L3. Analyzing brains from L3 through L5S1 larvae, we identified 21 genes with caste-specific transcription patterns (e.g., APC-4, GlcAT-P, fax, kr-h1 and shot, which encode proteins that are potentially involved in the development of brain tissues through controlling the cell proliferation rate (APC4, kr-h1 and fasciculation (GlcAT-P, fax, and shot. Shot, whose expression is known to be required for axon extension and cell proliferation, was found to be transcribed at significantly higher levels in L4 queens compared with worker larvae. Moreover, the protein encoded by this gene was immunolocalized to the cytoplasm of cells near the antennal lobe neuropiles and proximal to the Kenyon cells in the brains of L4 queens. In conclusion, during the larval period, the brains of queens are larger and develop more rapidly than workers' brains, which represents a developmental heterochrony reflecting the effect of the differential feeding regime of the two castes on nervous system development. Furthermore, this differential development is characterized by caste-specific transcriptional profiles of a set of genes, thus pointing to a link between differential nutrition and

  19. Nutritionally driven differential gene expression leads to heterochronic brain development in honeybee castes.

    Science.gov (United States)

    Moda, Lívia Maria; Vieira, Joseana; Guimarães Freire, Anna Cláudia; Bonatti, Vanessa; Bomtorin, Ana Durvalina; Barchuk, Angel Roberto; Simões, Zilá Luz Paulino

    2013-01-01

    The differential feeding regimes experienced by the queen and worker larvae of the honeybee Apis mellifera shape a complex endocrine response cascade that ultimately gives rise to differences in brain morphologies. Brain development analyzed at the morphological level from the third (L3) through fifth (L5) larval instars revealed an asynchrony between queens and workers. In the feeding phase of the last larval instar (L5F), two well-formed structures, pedunculi and calyces, are identifiable in the mushroom bodies of queens, both of which are not present in workers until a later phase (spinning phase, L5S). Genome-wide expression analyses and normalized transcript expression experiments monitoring specific genes revealed that this differential brain development starts earlier, during L3. Analyzing brains from L3 through L5S1 larvae, we identified 21 genes with caste-specific transcription patterns (e.g., APC-4, GlcAT-P, fax, kr-h1 and shot), which encode proteins that are potentially involved in the development of brain tissues through controlling the cell proliferation rate (APC4, kr-h1) and fasciculation (GlcAT-P, fax, and shot). Shot, whose expression is known to be required for axon extension and cell proliferation, was found to be transcribed at significantly higher levels in L4 queens compared with worker larvae. Moreover, the protein encoded by this gene was immunolocalized to the cytoplasm of cells near the antennal lobe neuropiles and proximal to the Kenyon cells in the brains of L4 queens. In conclusion, during the larval period, the brains of queens are larger and develop more rapidly than workers' brains, which represents a developmental heterochrony reflecting the effect of the differential feeding regime of the two castes on nervous system development. Furthermore, this differential development is characterized by caste-specific transcriptional profiles of a set of genes, thus pointing to a link between differential nutrition and differential

  20. Robust Scientists

    DEFF Research Database (Denmark)

    Gorm Hansen, Birgitte

    2012-01-01

    as the analytical framework for descri bing the complex relationship between academic science and its so called “external” habitat. Although relational skills and adaptability do seem to be at the heart of successful research management, the key to success does not lie with the ability to assimilate to industrial...... knowledge", Danish research policy seems to have helped develop politically and economically "robust scientists". Scientific robustness is acquired by way of three strategies: 1) tasting and discriminating between resources so as to avoid funding that erodes academic profiles and push scientists away from...... and industrial intere sts. The paper concludes by stressing the potential danger of policy habitats who have promoted the evolution of robust scientists based on a competitive system where only the fittest survive. Robust scientists, it is argued, have the potential to become a new “invasive species...

  1. Insight into transcription factor gene duplication from Caenorhabditis elegans Promoterome-driven expression patterns

    Directory of Open Access Journals (Sweden)

    Vidal Marc

    2007-01-01

    Full Text Available Abstract Background The C. elegans Promoterome is a powerful resource for revealing the regulatory mechanisms by which transcription is controlled pan-genomically. Transcription factors will form the core of any systems biology model of genome control and therefore the promoter activity of Promoterome inserts for C. elegans transcription factor genes was examined, in vivo, with a reporter gene approach. Results Transgenic C. elegans strains were generated for 366 transcription factor promoter/gfp reporter gene fusions. GFP distributions were determined, and then summarized with reference to developmental stage and cell type. Reliability of these data was demonstrated by comparison to previously described gene product distributions. A detailed consideration of the results for one C. elegans transcription factor gene family, the Six family, comprising ceh-32, ceh-33, ceh-34 and unc-39 illustrates the value of these analyses. The high proportion of Promoterome reporter fusions that drove GFP expression, compared to previous studies, led to the hypothesis that transcription factor genes might be involved in local gene duplication events less frequently than other genes. Comparison of transcription factor genes of C. elegans and Caenorhabditis briggsae was therefore carried out and revealed very few examples of functional gene duplication since the divergence of these species for most, but not all, transcription factor gene families. Conclusion Examining reporter expression patterns for hundreds of promoters informs, and thereby improves, interpretation of this data type. Genes encoding transcription factors involved in intrinsic developmental control processes appear acutely sensitive to changes in gene dosage through local gene duplication, on an evolutionary time scale.

  2. CREB-regulated transcription co-activator family stimulates promoter II-driven aromatase expression in preadipocytes.

    Science.gov (United States)

    Samarajeewa, Nirukshi U; Docanto, Maria M; Simpson, Evan R; Brown, Kristy A

    2013-08-01

    The dramatically increased prevalence of breast cancer after menopause is of great concern and is correlated with elevated local levels of estrogens. This is mainly due to an increase in aromatase expression driven by its proximal promoter II (PII). We have previously demonstrated that the CREB co-activator CRTC2 binds directly to PII and stimulates its activity via mechanisms involving LKB1-AMPK in response to prostaglandin E(2) (PGE(2)). There are three members of the CRTC family (CRTC1-3) and this study aimed to characterize the role of other CRTCs in the activation of aromatase PII. The expression and subcellular localization of CRTCs were examined in preadipocytes using qPCR and immunofluorescence. Under basal conditions, CRTC1 expression was the lowest, whereas CRTC3 transcripts were present at higher levels. Basally, CRTC2 and CRTC3 were mainly cytoplasmic and PGE(2) caused their nuclear translocation. Reporter assays and chromatin immunoprecipitation (ChIP) were performed to assess the effect of CRTCs on PII activity and binding. Basal PII activity was significantly increased with all CRTCs. Forskolin (FSK)/phorbol 12-myristate 13-acetate (PMA), to mimic PGE(2), resulted in a further significant increase in PII activity with all CRTCs, with CRTC2 and CRTC3 having greater effects. This was consistent with ChIP data showing an increased binding of CRTCs to PII with FSK/PMA. Moreover, gene silencing of CRTC2 and CRTC3 significantly reduced the FSK/PMA-mediated stimulation of aromatase activity. Interestingly, CRTCs acted cooperatively with CREB1 to increase PII activity, and both CREs were found to be essential for the maximal induction of PII activity by CRTCs. Phosphorylation of CRTC2 at its AMPK target site, Ser 171, dictated its subcellular localization, and the activation of aromatase PII in preadipocytes. In conclusion, this study demonstrates that aromatase regulation in primary human breast preadipocytes involves more than one CRTC.

  3. A robust approach to identifying tissue-specific gene expression regulatory variants using personalized human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Je-Hyuk Lee

    2009-11-01

    Full Text Available Normal variation in gene expression due to regulatory polymorphisms is often masked by biological and experimental noise. In addition, some regulatory polymorphisms may become apparent only in specific tissues. We derived human induced pluripotent stem (iPS cells from adult skin primary fibroblasts and attempted to detect tissue-specific cis-regulatory variants using in vitro cell differentiation. We used padlock probes and high-throughput sequencing for digital RNA allelotyping and measured allele-specific gene expression in primary fibroblasts, lymphoblastoid cells, iPS cells, and their differentiated derivatives. We show that allele-specific expression is both cell type and genotype-dependent, but the majority of detectable allele-specific expression loci remains consistent despite large changes in the cell type or the experimental condition following iPS reprogramming, except on the X-chromosome. We show that our approach to mapping cis-regulatory variants reduces in vitro experimental noise and reveals additional tissue-specific variants using skin-derived human iPS cells.

  4. Differential adenoassociated virus vector-driven expression of a neuropeptide Y gene in primary rat brain astroglial cultures after transfection with Sendai virosomes versus Lipofectin.

    Science.gov (United States)

    de Fiebre, C M; Wu, P; Notabartolo, D; Millard, W J; Meyer, E M

    1994-06-01

    The ability of Sendai virosomes or Lipofectin to introduce an AAV vector into primary rat brain astroglial cultures was characterized. The pJDT95npy vector was constructed by inserting rat NPY cDNA downstream from the indigenous AAV p5, p19 and p40 promoters in pJDT95. Lipofectin-mediated transfection with pJDT95npy (10 micrograms) resulted in pronounced expression of several NPY mRNA species: p5-driven (3.3 kb), p19-driven (2.7 kb) and p40-driven (0.6, 0.8, 1.1, and 1.8 kb). Exposure to virosomally encapsulated pJDT95npy (50 or 100 ng) resulted in transient expression of some p40-driven mRNA species (0.8 and 1.8 kb). Neither method produced astroglia cells which synthesized mature NPY immunoreactivity. This demonstrates that an AAV-derived vector can drive gene expression in astroglia, that Sendai virosomes can infuse vectors into astroglia, but that the amount of DNA infused in this manner may limit long term expression.

  5. Increasing a Robust Antigen-Specific Cytotoxic T Lymphocyte Response by FMDV DNA Vaccination with IL-9 Expressing Construct

    Directory of Open Access Journals (Sweden)

    Qiang Zou

    2010-01-01

    Full Text Available Various chemokines and cytokines as adjuvants can be used to improve efficacy of DNA vaccination. In this study, we sought to investigate if a DNA construct expressing IL-9 (designed as proV-IL9 as a molecular adjuvant enhance antigen specific immune responses elicited by the pcD-VP1 DNA vaccination. Mice immunized with pcD-VP1 combined with proV-IL9 developed a strong humoral response. In addition, the coinoculation induced significant higher level of antigen-specific cell proliferation and cytotoxic response. This agreed well with higher expression level of IFN-γ and perforin in CD8+ T cells, but not with IL-17 in these T cells. The results indicate that IL-9 induces the development of IFN-γ-producing CD8+ T cells (Tc1, but not the IL-17-producing CD8+ T cells (Tc17. Up-regulated expressions of BCL-2 and BCL-XL were exhibited in these Tc1 cells, suggesting that IL-9 may trigger antiapoptosis mechanism in these cells. Together, these results demonstrated that IL-9 used as molecular adjuvant could enhance the immunogenicity of DNA vaccination, in augmenting humoral and cellular responses and particularly promoting Tc1 activations. Thus, the IL-9 may be utilized as a potent Tc1 adjuvant for DNA vaccines.

  6. Cross-Dataset Analysis and Visualization Driven by Expressive Web Services

    Science.gov (United States)

    Alexandru Dumitru, Mircea; Catalin Merticariu, Vlad

    2015-04-01

    . The application offers a set of features to visualize and cross-compare the datasets. Users can select a region of interest in space and time on which an aerosol map layer is plotted. Hovmoeller time-latitude and time-longitude profiles can be displayed by selecting orthogonal cross-sections on the globe. Statistics about the selected dataset are also displayed in different text and plot formats. The datasets can also be cross-compared either by using the delta map tool or the merged map tool. For more advanced users, a WCPS query console is also offered allowing users to process their data with ad-hoc queries and then choose how to display the results. Overall, the user has a rich set of tools that can be used to visualize and cross-compare the aerosol datasets. With our application we have shown how the NASA WorldWind framework can be used to display results processed efficiently - and entirely - on the server side using the expressiveness of the OGC WCPS web-service. The application serves not only as a proof of concept of a new paradigm in working with large geospatial data but also as an useful tool for environmental data analysts.

  7. Midkine promoter-driven suicide gene expression and -mediated adenovirus replication produced cytotoxic effects to immortalised and tumour cells.

    Science.gov (United States)

    Yu, L; Hamada, K; Namba, M; Kadomatsu, K; Muramatsu, T; Matsubara, S; Tagawa, M

    2004-07-01

    We examined possible application of a regulatory region of midkine (MK) gene, which is frequently upregulated in a number of human tumours but not in normal cells, to cancer gene therapy. We examined transcriptional activity of the MK genomic fragments in paired cell lines, immortalized cells and their parental normal fibroblasts, and found that the MK fragments activated a fused reporter or a suicide gene preferentially in the immortalized cells. Recombinant adenoviruses (Ad), in which the MK fragment was inserted upstream to the E1A gene (AdMK), replicated preferentially in the immortalized cells and were cytotoxie to them. Human hepatocellular carcinoma cells were significantly susceptible to AdMK compared with human normal fibroblasts in vitro and the replication of AdMK was less than that of wild-type Ad in the infected fibroblasts. Hepatocellular carcinoma cells infected with AdMK did not form tumours in immunocompromised mice and intratumoural injection of AdMK into the hepatocellular carcinoma developed in mice retarded the subsequent tumour growth. Expression of E1A and necrosis of tumours were detected in AdMK-injected but not control Ad-injected cases. The MK promoter-driven suicide gene therapy and -mediated replicative Ad can thereby produce cytotoxic effects to immortalized and tumour cells with minimal damage to normal cells.

  8. Development of a robust protocol for gene expression analysis using formalin-fixed, paraffin-embedded liver transplant biopsy specimens.

    Science.gov (United States)

    Thompson, Emily; Burt, Alastair D; Barker, Catriona E; Kirby, John A; Brain, John G

    2013-09-01

    Liver transplant biopsies are routinely archived following formalin fixation and paraffin embedding and may provide an additional source of diagnostic information following transcriptomic biomarker analysis. This study was designed to compare gene transcription between resting and stressed biliary cells in culture, these cells after fixation and embedding and archival liver transplant biopsy tissue. The transcription of p21/WAF1 and transforming growth factor (TGF)-β1 showed similar changes in the fresh and embedded liver cells. However, the expression of TGF-β2 was markedly different between the fresh and embedded samples, suggesting that fixation can produce sequence-specific artefacts. Sufficient quantities of pure RNA were recovered from all the liver transplant biopsies to allow complementary DNA production. Measurement of the transcription of all three genes showed variability between the cases. Although the results for individual transcripts should be interpreted with care, these data do suggest the feasibility of performing a larger biomarker discovery studies using archival tissue.

  9. Population genetics of translational robustness

    OpenAIRE

    Wilke, Claus O; Drummond, D. Allan

    2005-01-01

    Recent work has shown that expression level is the main predictor of a gene’s evolutionary rate, and that more highly expressed genes evolve slower. A possible explanation for this observation is selection for proteins which fold properly despite mistranslation, in short selection for translational robustness. Translational robustness leads to the somewhat paradoxical prediction that highly expressed genes are extremely tolerant to missense substitutions but nevertheless evolve very slo...

  10. Human haematopoietic stem cells express Oct4 pseudogenes and lack the ability to initiate Oct4 promoter-driven gene expression

    Directory of Open Access Journals (Sweden)

    Strain Alastair J

    2010-03-01

    Full Text Available Abstract The transcription factor Oct4 is well defined as a key regulator of embryonic stem (ES cell pluripotency. In recent years, the role of Oct4 has purportedly extended to the self renewal and maintenance of multipotency in adult stem cell (ASC populations. This profile has arisen mainly from reports utilising reverse transcription-polymerase chain reaction (RT-PCR based methodologies and has since come under scrutiny following the discovery that many developmental genes have multiple pseudogenes associated with them. Six known pseudogenes exist for Oct4, all of which exhibit very high sequence homology (three >97%, and for this reason the generation of artefacts may have contributed to false identification of Oct4 in somatic cell populations. While ASC lack a molecular blueprint of transcription factors proposed to be involved with 'stemness' as described for ES cells, it is not unreasonable to assume that similar gene patterns may exist. The focus of this work was to corroborate reports that Oct4 is involved in the regulation of ASC self-renewal and differentiation, using a combination of methodologies to rule out pseudogene interference. Haematopoietic stem cells (HSC derived from human umbilical cord blood (UCB and various differentiated cell lines underwent RT-PCR, product sequencing and transfection studies using an Oct4 promoter-driven reporter. In summary, only the positive control expressed Oct4, with all other cell types expressing a variety of Oct4 pseudogenes. Somatic cells were incapable of utilising an exogenous Oct4 promoter construct, leading to the conclusion that Oct4 does not appear involved in the multipotency of human HSC from UCB.

  11. Differential protein expression using proteomics from a crustacean brine shrimp (Artemia sinica) under CO2-driven seawater acidification.

    Science.gov (United States)

    Chang, Xue-Jiao; Zheng, Chao-Qun; Wang, Yu-Wei; Meng, Chuang; Xie, Xiao-Lu; Liu, Hai-Peng

    2016-11-01

    Gradually increasing atmospheric CO2 partial pressure (pCO2) has caused an imbalance in carbonate chemistry and resulted in decreased seawater pH in marine ecosystems, termed seawater acidification. Anthropogenic seawater acidification is postulated to affect the physiology of many marine calcifying organisms. To understand the possible effects of seawater acidification on the proteomic responses of a marine crustacean brine shrimp (Artemia sinica) three groups of cysts were hatched and further raised in seawater at different pH levels (8.2 as control and 7.8 and 7.6 as acidification stress levels according to the predicted levels at the end of this century and next century, respectively) for 1, 7 and 14 days followed by examination of the protein expression changes via two-dimensional gel electrophoresis. Searches of protein databases revealed that 67 differential protein spots were altered due to lower pH level (7.6 and 7.8) stress in comparison to control groups (pH 8.2) by mass spectrometry. Generally, these differentially expressed proteins included the following: 1) metabolic process-related proteins involved in glycolysis and glucogenesis, nucleotide/amino acid/fatty acid metabolism, protein biosynthesis, DNA replication and apoptosis; 2) stress response-related proteins, such as peroxiredoxin, thioredoxin peroxidase, 70-kDa heat shock protein, Na/K ATPase, and ubiquinol-cytochrome c reductase; 3) immune defence-related proteins, such as prophenoloxidase and ferritin; 4) cytoskeletal-related proteins, such as myosin light chain, TCP1 subunit 2, tropomyosin and tubulin alpha chain; and 5) signal transduction-related proteins, such as phospholipase C-like protein, 14-3-3 zeta, translationally controlled tumour protein and RNA binding motif protein. Taken together, these data support the idea that CO2-driven seawater acidification may affect protein expression in the crustacean A. sinica and possibly also in other species that feed on brine shrimp in the

  12. Robust Chaos

    CERN Document Server

    Banerjee, S; Grebogi, C; Banerjee, Soumitro; Yorke, James A.; Grebogi, Celso

    1998-01-01

    It has been proposed to make practical use of chaos in communication, in enhancing mixing in chemical processes and in spreading the spectrum of switch-mode power suppies to avoid electromagnetic interference. It is however known that for most smooth chaotic systems, there is a dense set of periodic windows for any range of parameter values. Therefore in practical systems working in chaotic mode, slight inadvertent fluctuation of a parameter may take the system out of chaos. We say a chaotic attractor is robust if, for its parameter values there exists a neighborhood in the parameter space with no periodic attractor and the chaotic attractor is unique in that neighborhood. In this paper we show that robust chaos can occur in piecewise smooth systems and obtain the conditions of its occurrence. We illustrate this phenomenon with a practical example from electrical engineering.

  13. Robust Econometrics

    OpenAIRE

    Čίžek, Pavel; Härdle, Wolfgang Karl

    2006-01-01

    Econometrics often deals with data under, from the statistical point of view, non-standard conditions such as heteroscedasticity or measurement errors and the estimation methods need thus be either adopted to such conditions or be at least insensitive to them. The methods insensitive to violation of certain assumptions, for example insensitive to the presence of heteroscedasticity, are in a broad sense referred to as robust (e.g., to heteroscedasticity). On the other hand, there is also a mor...

  14. Robust RNAi-based resistance to mixed infection of three viruses in soybean plants expressing separate short hairpins from a single transgene.

    Science.gov (United States)

    Zhang, Xiuchun; Sato, Shirley; Ye, Xiaohong; Dorrance, Anne E; Morris, T Jack; Clemente, Thomas E; Qu, Feng

    2011-11-01

    Transgenic plants expressing double-stranded RNA (dsRNA) of virus origin have been previously shown to confer resistance to virus infections through the highly conserved RNA-targeting process termed RNA silencing or RNA interference (RNAi). In this study we applied this strategy to soybean plants and achieved robust resistance to multiple viruses with a single dsRNA-expressing transgene. Unlike previous reports that relied on the expression of one long inverted repeat (IR) combining sequences of several viruses, our improved strategy utilized a transgene designed to express several shorter IRs. Each of these short IRs contains highly conserved sequences of one virus, forming dsRNA of less than 150 bp. These short dsRNA stems were interspersed with single-stranded sequences to prevent homologous recombination during the transgene assembly process. Three such short IRs with sequences of unrelated soybean-infecting viruses (Alfalfa mosaic virus, Bean pod mottle virus, and Soybean mosaic virus) were assembled into a single transgene under control of the 35S promoter and terminator of Cauliflower mosaic virus. Three independent transgenic lines were obtained and all of them exhibited strong systemic resistance to the simultaneous infection of the three viruses. These results demonstrate the effectiveness of this very straight forward strategy for engineering RNAi-based virus resistance in a major crop plant. More importantly, our strategy of construct assembly makes it easy to incorporate additional short IRs in the transgene, thus expanding the spectrum of virus resistance. Finally, this strategy could be easily adapted to control virus problems of other crop plants.

  15. Population genetics of translational robustness.

    Science.gov (United States)

    Wilke, Claus O; Drummond, D Allan

    2006-05-01

    Recent work has shown that expression level is the main predictor of a gene's evolutionary rate and that more highly expressed genes evolve slower. A possible explanation for this observation is selection for proteins that fold properly despite mistranslation, in short selection for translational robustness. Translational robustness leads to the somewhat paradoxical prediction that highly expressed genes are extremely tolerant to missense substitutions but nevertheless evolve very slowly. Here, we study a simple theoretical model of translational robustness that allows us to gain analytic insight into how this paradoxical behavior arises.

  16. Robust Scientists

    DEFF Research Database (Denmark)

    Gorm Hansen, Birgitte

    The concepts of “socially robust knowledge” and “mode 2 knowledge production” (Nowotny 2003, Gibbons et al. 1994) have migrated from STS into research policy practices. Both STS-scholars and policy makers have been known to propomote the idea that the way forward for today’s scientist is to jump...... from the ivory tower and learn how to create high-flying synergies with citizens, corporations and governments. In STS as well as in Danish research policy it has thus been argued that scientists will gain more support and enjoy greater success in their work by “externalizing” their research...... and adapting their interests to the needs of outside actors. However, when studying the concrete strategies of such successful scientists, matters seem a bit more complicated. Based on interviews with a plant biologist working in GMO the paper uses the biological concepts of field participants...

  17. Robust factorization

    DEFF Research Database (Denmark)

    Aanæs, Henrik; Fisker, Rune; Åström, Kalle;

    2002-01-01

    Factorization algorithms for recovering structure and motion from an image stream have many advantages, but they usually require a set of well-tracked features. Such a set is in generally not available in practical applications. There is thus a need for making factorization algorithms deal...... effectively with errors in the tracked features. We propose a new and computationally efficient algorithm for applying an arbitrary error function in the factorization scheme. This algorithm enables the use of robust statistical techniques and arbitrary noise models for the individual features....... These techniques and models enable the factorization scheme to deal effectively with mismatched features, missing features, and noise on the individual features. The proposed approach further includes a new method for Euclidean reconstruction that significantly improves convergence of the factorization algorithms...

  18. Exponential sensitivity of noise-driven switching in genetic networks

    Science.gov (United States)

    Mehta, Pankaj; Mukhopadhyay, Ranjan; Wingreen, Ned S.

    2008-06-01

    There is increasing experimental evidence that cells can utilize biochemical noise to switch probabilistically between distinct gene-expression states. In this paper, we demonstrate that such noise-driven switching is dominated by tails of probability distributions and is therefore exponentially sensitive to changes in physiological parameters such as transcription and translation rates. Exponential sensitivity limits the robustness of noise-driven switching, suggesting cells may use other mechanisms in order to switch reliably. We discuss our results in the context of competence in the bacterium Bacillus subtilis.

  19. Simian Immunodeficiency Virus Targeting of CXCR3(+) CD4(+) T Cells in Secondary Lymphoid Organs Is Associated with Robust CXCL10 Expression in Monocyte/Macrophage Subsets.

    Science.gov (United States)

    Fujino, Masayuki; Sato, Hirotaka; Okamura, Tomotaka; Uda, Akihiko; Takeda, Satoshi; Ahmed, Nursarat; Shichino, Shigeyuki; Shiino, Teiichiro; Saito, Yohei; Watanabe, Satoru; Sugimoto, Chie; Kuroda, Marcelo J; Ato, Manabu; Nagai, Yoshiyuki; Izumo, Shuji; Matsushima, Kouji; Miyazawa, Masaaki; Ansari, Aftab A; Villinger, Francois; Mori, Kazuyasu

    2017-07-01

    Glycosylation of Env defines pathogenic properties of simian immunodeficiency virus (SIV). We previously demonstrated that pathogenic SIVmac239 and a live-attenuated, quintuple deglycosylated Env mutant (Δ5G) virus target CD4(+) T cells residing in different tissues during acute infection. SIVmac239 and Δ5G preferentially infected distinct CD4(+) T cells in secondary lymphoid organs (SLOs) and within the lamina propria of the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Here, we studied the host responses relevant to SIV targeting of CXCR3(+) CCR5(+) CD4(+) T cells in SLOs. Genome-wide transcriptome analyses revealed that Th1-polarized inflammatory responses, defined by expression of CXCR3 chemokines, were distinctly induced in the SIVmac239-infected animals. Consistent with robust expression of CXCL10, CXCR3(+) T cells were depleted from blood in the SIVmac239-infected animals. We also discovered that elevation of CXCL10 expression in blood and SLOs was secondary to the induction of CD14(+) CD16(+) monocytes and MAC387(+) macrophages, respectively. Since the significantly higher levels of SIV infection in SLOs occurred with a massive accumulation of infiltrated MAC387(+) macrophages, T cells, dendritic cells (DCs), and residential macrophages near high endothelial venules, the results highlight critical roles of innate/inflammatory responses in SIVmac239 infection. Restricted infection in SLOs by Δ5G also suggests that glycosylation of Env modulates innate/inflammatory responses elicited by cells of monocyte/macrophage/DC lineages.IMPORTANCE We previously demonstrated that a pathogenic SIVmac239 virus and a live-attenuated, deglycosylated mutant Δ5G virus infected distinct CD4(+) T cell subsets in SLOs and the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Accordingly, infections with SIVmac239, but not with Δ5G

  20. Expression-robust 3D face recognition via weighted sparse representation of multi-scale and multi-component local normal patterns

    KAUST Repository

    Li, Huibin

    2014-06-01

    In the theory of differential geometry, surface normal, as a first order surface differential quantity, determines the orientation of a surface at each point and contains informative local surface shape information. To fully exploit this kind of information for 3D face recognition (FR), this paper proposes a novel highly discriminative facial shape descriptor, namely multi-scale and multi-component local normal patterns (MSMC-LNP). Given a normalized facial range image, three components of normal vectors are first estimated, leading to three normal component images. Then, each normal component image is encoded locally to local normal patterns (LNP) on different scales. To utilize spatial information of facial shape, each normal component image is divided into several patches, and their LNP histograms are computed and concatenated according to the facial configuration. Finally, each original facial surface is represented by a set of LNP histograms including both global and local cues. Moreover, to make the proposed solution robust to the variations of facial expressions, we propose to learn the weight of each local patch on a given encoding scale and normal component image. Based on the learned weights and the weighted LNP histograms, we formulate a weighted sparse representation-based classifier (W-SRC). In contrast to the overwhelming majority of 3D FR approaches which were only benchmarked on the FRGC v2.0 database, we carried out extensive experiments on the FRGC v2.0, Bosphorus, BU-3DFE and 3D-TEC databases, thus including 3D face data captured in different scenarios through various sensors and depicting in particular different challenges with respect to facial expressions. The experimental results show that the proposed approach consistently achieves competitive rank-one recognition rates on these databases despite their heterogeneous nature, and thereby demonstrates its effectiveness and its generalizability. © 2014 Elsevier B.V.

  1. Combining multiple hypothesis testing and affinity propagation clustering leads to accurate, robust and sample size independent classification on gene expression data

    Directory of Open Access Journals (Sweden)

    Sakellariou Argiris

    2012-10-01

    Full Text Available Abstract Background A feature selection method in microarray gene expression data should be independent of platform, disease and dataset size. Our hypothesis is that among the statistically significant ranked genes in a gene list, there should be clusters of genes that share similar biological functions related to the investigated disease. Thus, instead of keeping N top ranked genes, it would be more appropriate to define and keep a number of gene cluster exemplars. Results We propose a hybrid FS method (mAP-KL, which combines multiple hypothesis testing and affinity propagation (AP-clustering algorithm along with the Krzanowski & Lai cluster quality index, to select a small yet informative subset of genes. We applied mAP-KL on real microarray data, as well as on simulated data, and compared its performance against 13 other feature selection approaches. Across a variety of diseases and number of samples, mAP-KL presents competitive classification results, particularly in neuromuscular diseases, where its overall AUC score was 0.91. Furthermore, mAP-KL generates concise yet biologically relevant and informative N-gene expression signatures, which can serve as a valuable tool for diagnostic and prognostic purposes, as well as a source of potential disease biomarkers in a broad range of diseases. Conclusions mAP-KL is a data-driven and classifier-independent hybrid feature selection method, which applies to any disease classification problem based on microarray data, regardless of the available samples. Combining multiple hypothesis testing and AP leads to subsets of genes, which classify unknown samples from both, small and large patient cohorts with high accuracy.

  2. Cre/loxP-mediated excision of a neomycin resistance expression unit from an integrated retroviral vector increases long terminal repeat-driven transcription in human hematopoietic cells.

    Science.gov (United States)

    Fernex, C; Dubreuil, P; Mannoni, P; Bagnis, C

    1997-01-01

    Recombinant retroviruses are currently the most attractive vehicles for gene transfer into hematopoietic cells. Retroviral vectors often contain an easily selectable marker gene in addition to the gene of interest. However, the presence and selection for expression of the selectable gene often result in a significant reduction of the expression of the gene of interest in the transduced cells. In order to circumvent this problem, we have developed a Cre/loxP recombination system for specific excision of the selectable expression unit from integrated retroviruses. A retroviral vector, containing both a neomycin resistance expression unit flanked by loxP sites and granulocyte-macrophage colony-stimulating factor cDNA, was used to transduce the human hematopoietic K-562 cell line. Four transduced cell clones were then superinfected with a retrovirus containing a Cre recombinase expression unit. Molecular analyses of 30 doubly transduced subclones showed a strict correlation between cre expression and loxP-flanked selectable cassette excision, thus implying that Cre recombinase activity is very efficient in a retroviral context. Moreover, the excision of the selectable cassette results in a significant increase of granulocyte-macrophage colony-stimulating factor transcription driven by the retroviral promoter. PMID:9311833

  3. Shaping Robust System through Evolution

    CERN Document Server

    Kaneko, Kunihiko

    2008-01-01

    Biological functions are generated as a result of developmental dynamics that form phenotypes governed by genotypes. The dynamical system for development is shaped through genetic evolution following natural selection based on the fitness of the phenotype. Here we study how this dynamical system is robust to noise during development and to genetic change by mutation. We adopt a simplified transcription regulation network model to govern gene expression, which gives a fitness function. Through simulations of the network that undergoes mutation and selection, we show that a certain level of noise in gene expression is required for the network to acquire both types of robustness. The results reveal how the noise that cells encounter during development shapes any network's robustness, not only to noise but also to mutations. We also establish a relationship between developmental and mutational robustness through phenotypic variances caused by genetic variation and epigenetic noise. A universal relationship betwee...

  4. The VviMYB80 Gene is Abnormally Expressed in Vitis vinifera L. cv. 'Zhong Shan Hong' and its Expression in Tobacco Driven by the 35S Promoter Causes Male Sterility.

    Science.gov (United States)

    Zheng, Huan; Yu, Xiaojuan; Yuan, Yue; Zhang, Yaguang; Zhang, Zhen; Zhang, Jiyu; Zhang, Meng; Ji, Chenfei; Liu, Qian; Tao, Jianmin

    2016-03-01

    Anther development is a very precise and complicated process. In Arabidopsis, the AtMYB80 transcription factor regulates genes involved in pollen development and controls the timing of tapetal programmed cell death (PCD). In this study, we isolated and characterized cDNA for VviMYB80 expressed in flower buds of male-sterile Vitis vinifera L. cv. 'Zhong Shan Hong', a late-maturing cultivar derived from self-progeny of cv. 'Wink'. VviMYB80 belongs to the MYB80 subfamily and clusters with AtMYB35/TDF1 in a distinct clade. We found that in flower buds, expression of the VviMYB80 gene in cv. 'Zhong Shan Hong' sharply increased at the tetrad stage, resulting in a higher and earlier transcript level than that found in cv. 'Wink'. Expression of the VviMYB80 gene, driven by the 35S promoter, caused pleiotropic effects on the stamens, including smaller and shriveled anthers, delayed dehiscence, fewer seeds, shorter anther filaments, distorted pollen shape and a lack of cytoplasm, with the tapetum exhibiting hypertrophy in transformed tobacco. These results suggest that VviMYB80 may play an important role in stamen development and that expression of VviMYB80 driven by the 35S promoter in tobacco induces male sterility. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. Fine specificity of monoclonal antibodies directed at human T cell receptor variable regions: comparison with oligonucleotide-driven amplification for evaluation of V beta expression.

    Science.gov (United States)

    Diu, A; Romagné, F; Genevée, C; Rocher, C; Bruneau, J M; David, A; Praz, F; Hercend, T

    1993-07-01

    Seven distinct anti-human T cell receptor (TcR) V region monoclonal antibodies (mAb) were generated by immunizing mice with either human T cell lines or transfected murine cells expressing human TcR V beta genes. The specificity of these reagents was determined as follows: T cells recognized by each mAb were purified from the peripheral blood of healthy donors and TcR transcripts expressed in these cells were analyzed using oligonucleotide-driven amplification and cDNA sequencing. Four mAb were found to delineate the V beta 3, V beta 8, V beta 17 and V beta 19 subfamilies, respectively. The remaining reagents recognize subsets within the V beta 2, V beta 5 and V beta 13 subfamilies. Reactivity of the mAb with circulating T cells from 18 unrelated healthy individuals was determined. Limited variability was found from an individual to another. In four donors, mAb staining was compared to oligonucleotide-driven amplification for evaluation of V beta 3, V beta 8, V beta 17 and V beta 19 subfamily expression in the peripheral blood. Although the V gene subfamily-specific oligonucleotides used in this study belong to a carefully controlled series, our results show that this method does not give an accurate estimate of the percentage of peripheral T cells expressing a given TcR beta chain. The present data confirm the necessity to establish a complete set of well-characterized monoclonal reagents to study human T cell responses.

  6. MicroRNA expression in abdominal and gluteal adipose tissue is associated with mRNA expression levels and partly genetically driven.

    OpenAIRE

    Mattias Rantalainen; Herrera, Blanca M; George Nicholson; Rory Bowden; Wills, Quin F.; Min, Josine L.; Neville, Matt J.; Amy Barrett; Maxine Allen; Rayner, Nigel W; Jan Fleckner; McCarthy, Mark I; Zondervan, Krina T.; Fredrik Karpe; Holmes, Chris C.

    2011-01-01

    To understand how miRNAs contribute to the molecular phenotype of adipose tissues and related traits, we performed global miRNA expression profiling in subcutaneous abdominal and gluteal adipose tissue of 70 human subjects and characterised which miRNAs were differentially expressed between these tissues. We found that 12% of the miRNAs were significantly differentially expressed between abdominal and gluteal adipose tissue (FDR adjusted p

  7. Robustness of Cantor diffractals.

    Science.gov (United States)

    Verma, Rupesh; Sharma, Manoj Kumar; Banerjee, Varsha; Senthilkumaran, Paramasivam

    2013-04-08

    Diffractals are electromagnetic waves diffracted by a fractal aperture. In an earlier paper, we reported an important property of Cantor diffractals, that of redundancy [R. Verma et. al., Opt. Express 20, 8250 (2012)]. In this paper, we report another important property, that of robustness. The question we address is: How much disorder in the Cantor grating can be accommodated by diffractals to continue to yield faithfully its fractal dimension and generator? This answer is of consequence in a number of physical problems involving fractal architecture.

  8. The ALK inhibitor PF-06463922 is effective as a single agent in neuroblastoma driven by expression of ALK and MYCN

    Directory of Open Access Journals (Sweden)

    J. Guan

    2016-09-01

    Full Text Available The first-in-class inhibitor of ALK, c-MET and ROS1, crizotinib (Xalkori, has shown remarkable clinical efficacy in treatment of ALK-positive non-small cell lung cancer. However, in neuroblastoma, activating mutations in the ALK kinase domain are typically refractory to crizotinib treatment, highlighting the need for more potent inhibitors. The next-generation ALK inhibitor PF-06463922 is predicted to exhibit increased affinity for ALK mutants prevalent in neuroblastoma. We examined PF-06463922 activity in ALK-driven neuroblastoma models in vitro and in vivo. In vitro kinase assays and cell-based experiments examining ALK mutations of increasing potency show that PF-06463922 is an effective inhibitor of ALK with greater activity towards ALK neuroblastoma mutants. In contrast to crizotinib, single agent administration of PF-06463922 caused dramatic tumor inhibition in both subcutaneous and orthotopic xenografts as well as a mouse model of high-risk neuroblastoma driven by Th-ALKF1174L/MYCN. Taken together, our results suggest PF-06463922 is a potent inhibitor of crizotinib-resistant ALK mutations, and highlights an important new treatment option for neuroblastoma patients.

  9. Hepatitis C Virus Activates a Neuregulin-Driven Circuit to Modify Surface Expression of Growth Factor Receptors of the ErbB Family.

    Directory of Open Access Journals (Sweden)

    Sabine Stindt

    Full Text Available Recently, the epidermal growth factor (EGF receptor (EGFR, a member of the ErbB receptor family, and its down-stream signalling have been identified as co-factors for HCV entry and replication. Since EGFR also functions as a heterodimer with other ErbB receptor family members, the subject of the present study was to investigate a possible viral interference with these cellular components. By using genotype 1b replicon cells as well as an infection-based system we found that while transcript and protein levels of EGFR and ErbB2 were up-regulated or unaffected, respectively, HCV induced a substantial reduction of ErbB3 and ErbB4 expression. Down-regulation of ErbB3 expression by HCV involves specificity protein (Sp1-mediated induction of Neuregulin (NRG1 expression as well as activation of Akt. Consistently, at transcript level disruption of ErbB3 expression by HCV can be prevented by knockdown of NRG1 or Sp1 expression, whereas reconstitution of ErbB3 protein levels requires inhibition of HCV-induced NRG1 expression and of Akt activity. Interestingly, the NRG1-mediated suppression of ErbB3 expression by HCV results in an enhanced expression of EGFR and ErbB2 on the cell surface, which can be mimicked by siRNA-mediated knockdown of ErbB3 expression. These data delineate a novel mechanism enabling HCV to sway the composition of the ErbB family members on the surface of its host cell by an NRG1-driven circuit and unravels a yet unknown cross-regulation between ErbB3 and the two other family members ErbB2 and EGFR. The shift of the receptor surface expression of the ErbB family towards enhanced expression of ErbB2 and EGFR triggered by HCV was found to promote viral RNA replication and infectivity. This suggests that HCV rearranges expression of ErbB family members to adapt the cellular environment to its requirements.

  10. [Expression of target gene in eukaryotic cells driven by prokaryotic T7 promoter and its RNA polymerase].

    Science.gov (United States)

    Yuan, Zhi-Gang; Zhang, Jin-Ping; Chu, Yi-Wei; Wang, Ying; Xu, Wei; Xiong, Si-Dong

    2005-03-01

    To enhance the efficiency of the expression of target gene in eukaryotic cells, one of the strongest prokaryotic expression systems, the T7 RNA polymerase and T7 promoter, was introduced into eukaryotic cells. A duel-plasmid gene expression system of T7 bacteriophage components was developed; one containing the T7 phage RNA polymerase gene under the control of eukaryotic promoter CMV (pCMV-T7pol) and the other (pT7IRES) containing the T7 promoter and T7 terminator as well as EMCV IRES. To test the feasibility of this plasmid system for eukaryotic expression, hepatitis B virus envelop HBV preS2/S was used to construct pT7IRES-HBs. The target genes were expressed efficiently by the eukaryonized prokaryotic expression system in a variety of the cells indicating C2C12, SP2/0, NIH3T3 and BALB/c 3T3, suggesting the potential applications of the expression system in gene therapy and gene immunization.

  11. A new idea for simple and rapid monitoring of gene expression: requirement of nucleotide sequences encoding an N-terminal HA tag in the T7 promoter-driven expression in E. coli.

    Science.gov (United States)

    Moon, Jeong-Mi; Kim, Goo-Young; Rhim, Hyangshuk

    2012-10-01

    Mammalian expression vectors are used to overexpress genes of interest in mammalian cells. High temperature requirement protein A1 (HtrA1), used as a specific target, was expressed from the pHA-M-HtrA1 plasmid in HEK293T cells, inducing cell death. Expression of HtrA1 was driven by the pHA-M-HtrA1 mammalian expression vector in E. coli resulting in growth suppression of E. coli in an HtrA1 serine protease-dependent manner. By using various combinations of promoters, target genes and N-terminal tags, the T7 promoter and N-terminal HA tag in the mammalian expression vector were shown to be responsible for expression of target genes in E. coli. Thus the pHA-M-HtrA1 plasmid can be used as a novel, rapid pre-test system for expression and cytotoxicity of the specific target gene in E. coli before assessing its functions in mammalian cells.

  12. Widespread neuron-specific transgene expression in brain and spinal cord following synapsin promoter-driven AAV9 neonatal intracerebroventricular injection.

    Science.gov (United States)

    McLean, Jesse R; Smith, Gaynor A; Rocha, Emily M; Hayes, Melissa A; Beagan, Jonathan A; Hallett, Penelope J; Isacson, Ole

    2014-07-25

    Adeno-associated viral (AAV) gene transfer holds great promise for treating a wide-range of neurodegenerative disorders. The AAV9 serotype crosses the blood-brain barrier and shows enhanced transduction efficiency compared to other serotypes, thus offering advantageous targeting when global transgene expression is required. Neonatal intravenous or intracerebroventricular (i.c.v.) delivery of recombinant AAV9 (rAAV9) have recently proven effective for modeling and treating several rodent models of neurodegenerative disease, however, the technique is associated with variable cellular tropism, making tailored gene transfer a challenge. In the current study, we employ the human synapsin 1 (hSYN1) gene promoter to drive neuron-specific expression of green fluorescent protein (GFP) after neonatal i.c.v. injection of rAAV9 in mice. We observed widespread GFP expression in neurons throughout the brain, spinal cord, and peripheral nerves and ganglia at 6 weeks-of-age. Region-specific quantification of GFP expression showed high neuronal transduction rates in substantia nigra pars reticulata (43.9±5.4%), motor cortex (43.5±3.3%), hippocampus (43.1±2.7%), cerebellum (29.6±2.3%), cervical spinal cord (24.9±3.9%), and ventromedial striatum (16.9±4.3%), among others. We found that 14.6±2.2% of neuromuscular junctions innervating the gastrocnemius muscle displayed GFP immunoreactivity. GFP expression was identified in several neuronal sub-types, including nigral tyrosine hydroxylase (TH)-positive dopaminergic cells, striatal dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32)-positive neurons, and choline acetyltransferase (ChAT)-positive motor neurons. These results build on contemporary gene transfer techniques, demonstrating that the hSYN1 promoter can be used with rAAV9 to drive robust neuron-specific transgene expression throughout the nervous system.

  13. NF-kappaB-driven STAT2 and CCL2 expression in astrocytes in response to brain injury

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Babcock, Alicia A; Owens, Trevor

    2008-01-01

    Tissue response to injury includes expression of genes encoding cytokines and chemokines. These regulate entry of immune cells to the injured tissue. The synthesis of many cytokines and chemokines involves NF-kappaB and signal transducers and activators of transcription (STAT). Injury to the CNS...... induces glial response. Astrocytes are the major glial population in the CNS. We examined expression of STATs and the chemokine CCL2 and their relationship to astroglial NF-kappaB signaling in the CNS following axonal transection. Double labeling with Mac-1/CD11b and glial fibrillary acidic protein......-regulation and phosphorylation were NF-kappaB -dependent since they did not occur in the lesion-reactive hippocampus of transgenic mice with specific inhibition of NF-kappaB activation in astrocytes. We further showed that lack of NF-kappaB signaling significantly reduced injury-induced CCL2 expression as well as leukocyte...

  14. Copper induction of enhanced green fluorescent protein expression in Pleurotus ostreatus driven by laccase poxa1b promoter.

    Science.gov (United States)

    Amore, Antonella; Honda, Yoichi; Faraco, Vincenza

    2012-12-01

    In silico analyses of several laccase promoter sequences have shown the presence of many different responsive elements differentially distributed along the promoter sequences. Analysis of Pleurotus ostreatus laccase promoter poxa1b extending around 1400-bp upstream of the start codon showed the presence of several putative response elements, such as 10 metal-responsive elements. Development of a system for in vivo analysis of P. ostreatus laccase promoter poxa1b by enhanced green fluorescent protein expression was carried out, based on a polyethylene glycol-mediated procedure for fungal transformation. Quantitative measurement of fluorescence expressed in P. ostreatus transformants grown in the presence and in the absence of copper sulfate was performed, demonstrating an increase in expression level induced by the metal.

  15. Robustness of Structures

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard

    2011-01-01

    robust design as well as strategies for maintaining the robustness of existing structures throughout their service life. This paper describes an overall theoretical framework for assessing robustness of structures developed within WG1 “Robustness of structures”. Robustness can be defined in different......An important aspect of the COST Action TU0601 “Robustness of structures” concerns the development of a theoretically sound basis for the assessment of robustness and acceptance criteria for structural robustness which can form the basis for development of practical relevant methods for ensuring...

  16. Delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA as a cancer therapeutic: a proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Lin KY

    2016-05-01

    Full Text Available Kun-Yuan Lin,1 Siao Muk Cheng,2 Shing-Ling Tsai,2 Ju-Ya Tsai,1 Chun-Hui Lin,1 Chun Hei Antonio Cheung1,2 1Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC; 2Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC Abstract: Survivin is a member of the inhibitor-of-apoptosis proteins family. It is overexpressed in many different cancer types but not in the differentiated normal tissue. In addition, overexpression of survivin promotes cancer cell survival and induces chemotherapeutic drug resistance, making it an attractive target for new anticancer interventions. Despite survivin being a promising molecular target for anticancer treatment, it is widely accepted that survivin is only a “semi-druggable” target. Therefore, it is important to develop a new strategy to target survivin for anticancer treatment. In this study, we constructed a novel survivin promoter-driven full-length antisense survivin (pSur/AS-Sur expression plasmid DNA. Promoter activity assay revealed that the activity of the survivin promoter of pSur/AS-Sur correlated with the endogenous expression of survivin at the transcriptional level in the transfected A549, MDA-MB-231, and PANC-1 cancer cells. Western blot analysis showed that liposomal delivery of pSur/AS-Sur successfully downregulated the expression of survivin in A549, MBA-MB-231, and PANC-1 cells in vitro. In addition, delivery of pSur/AS-Sur induced autophagy, caspase-dependent apoptosis, and caspase-independent apoptosis as indicated by the increased LC3B-II conversion, autophagosome formation, caspase-9/-3 and poly(ADP-ribose polymerase-1 cleavage, and apoptosis-inducing factor nuclear translocation in A549, MBA-MB-231, and PANC-1 cells. Importantly, liposomal delivery of pSur/AS-Sur was also capable of decreasing the proliferation of the survivin/MDR1 coexpressing multidrug-resistant KB-TAX50 cancer cells and

  17. Age-related gene expression in luminal epithelial cells is driven by a microenvironment made from myoepithelial cells.

    Science.gov (United States)

    Miyano, Masaru; Sayaman, Rosalyn W; Stoiber, Marcus H; Lin, Chun-Han; Stampfer, Martha R; Brown, James B; LaBarge, Mark A

    2017-10-09

    Luminal epithelial cells in the breast gradually alter gene and protein expression with age, appearing to lose lineage-specificity by acquiring myoepithelial-like characteristics. We hypothesize that the luminal lineage is particularly sensitive to microenvironment changes, and age-related microenvironment changes cause altered luminal cell phenotypes. To evaluate the effects of different microenvironments on the fidelity of epigenetically regulated luminal and myoepithelial gene expression, we generated a set of lineage-specific probes for genes that are controlled through DNA methylation. Culturing primary luminal cells under conditions that favor myoepithelial propogation led to their reprogramming at the level of gene methylation, and to a more myoepithelial-like expression profile. Primary luminal cells' lineage-specific gene expression could be maintained when they were cultured as bilayers with primary myoepithelial cells. Isogenic stromal fibroblast co-cultures were unable to maintain the luminal phenotype. Mixed-age luminal-myoepithelial bilayers revealed that luminal cells adopt transcription and methylation patterns consistent with the chronological age of the myoepithelial cells. We provide evidence that the luminal epithelial phenotype is exquisitely sensitive to microenvironment conditions, and that states of aging are cell non-autonomously communicated through microenvironment cues over at least one cell diameter.

  18. Tissue-specific expression of GFP reporter gene in germline driven by GATA-2 promoter and enhancers in zebrafish

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    GATA-2,a transcription factor,is expressed in several types of blood cells and in the central nervous system (CNS),and regulates the differentiation of these cells.We have obtained five zebrafish transgenic germlines that carry and express the green fluorescent protein (GFP) gene ligated to various 5′flanking sequences of zebrafish GATA-2 gene.The spatial pattern of GFP expression varies,mainly depending on which regulatory sequence is used,among the germlines.In some of the germlines,the expression of GFP is restricted to the CNS and the enveloping layer (EVL) cells,while in some other lines GFP is observed only in the CNS.It is noted that the intensity of GFP in the transgenic fish remain unchanged after a six-generation passage of the transgenes.The transgenic fish could find its uses in the future in generating tissue-specific,even cellspecific mutant fish and in functional study of related genes through transgenesis.

  19. Analysis of cell-specificity and variegation of transgene expression driven by salmon prolactin promoter in stable lines of transgenic rainbow trout.

    Science.gov (United States)

    Uzbekova, Svetlana; Amoros, Claire; Cauty, Chantale; Mambrini, Muriel; Perrot, Elizabeth; Hew, Choy L; Chourrout, Daniel; Prunet, Patrick

    2003-04-01

    In order to identify the specificity and functionality of salmon prolactin (sPRL) promoter, transgenic rainbow trout carrying a construct comprising the 2.4 kb fragment of the 5' flanking region of Atlantic Chinook sPRL gene fused either to the reporter genes cat (sPRL-cat) or lacZ (sPRL-lacZ) were produced. sPRL-cat in transgenic F0 fish expressed strongly CAT only in the pituitary gland. Transgenic in F1-F4 lines harbouring sPRL-lacZ expressed beta-galactosidase (beta-gal) only in the follicular PRL-producing cells of the adenohypophysis. We observed heterocellular, mosaic distribution of beta-gal within PRL cell population and enormous variation of lacZ expression level between the littermates in the same transgenic line. Regardless of the transgene copy number, age or sex of transgenic fish, beta-gal expression was lactotroph-specific but variegated in all the nine F2 hemizygous lines analysed. One line harbouring a multicopy integration was followed up to F4 generation: the transgene was transmitted without modifications. Analysis of genomic DNA from pituitaries showed that lacZ sequences were highly methylated. LacZ expression was low and its transcripts, analysed by in situ hybridisation, showed a mosaic distribution within the pituitary gland. These data suggest that variegated expression of lacZ can occur at the transcription level owing to the silencing effect of lacZ gene. After proving the tissue-specific expression of reporter genes driven by the sPRL promoter, we tried to obtain the genetic ablation of PRL-producing cells,by transferring the same construct comprising diphtheria toxin DT-A gene (tox). However, the high mortality rate of sPRL-tox transformed embryos has embedded this study and no transgenic fish expressing tox were produced. The appropriateness of using transgenic strategies to analyse gene function in Salmonids is discussed, especially the implications of the multicopy integration patterns and of the variegated transgene expression.

  20. Expression of ipt gene driven by tomato fruit specific promoter and its effects on fruit development of tomato

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Fruit specific promoter (2A12) from Lycopersicom esculentum and cDNA of isopentenyl-transferase (ipt) from Ti plasmid of Agrobacterium tumerfaciens C58 were cloned by PCR procedure respectively. Two plant expression vectors with 2A12/gus or 2A12/ipt were respectively constructed. These two chimeric genes were transferred into tomato by Agrobacterium mediated procedure. The results of Southern hybridization showed that the fusion genes had been integrated into tomatoes. The result of gus histochemical staining showed that 2A12 had high fruit specific expressive capability in transgenic tomato. The ipt expression resulted in accumulation of high level of cytokinins (CTKs) in fruit lead to developmental changes in fruits and seeds. The fruit of ipt transformed tomato had the hyperplastic placenta with very few seeds or even seedless. The shelf life of transgenic fruits elongated for 1-2 weeks. The ratio of fruit set, the dry weight of fruit and the crude protein content in fruit were increased, while the soluble sugar of fruits decreased.

  1. A Robust System for Natural Spoken Dialogue

    CERN Document Server

    Allen, J F; Ringger, E K; Sikorski, T; Allen, James F.; Miller, Bradford W.; Ringger, Eric K.; Sikorski, Teresa

    1996-01-01

    This paper describes a system that leads us to believe in the feasibility of constructing natural spoken dialogue systems in task-oriented domains. It specifically addresses the issue of robust interpretation of speech in the presence of recognition errors. Robustness is achieved by a combination of statistical error post-correction, syntactically- and semantically-driven robust parsing, and extensive use of the dialogue context. We present an evaluation of the system using time-to-completion and the quality of the final solution that suggests that most native speakers of English can use the system successfully with virtually no training.

  2. Methods for robustness programming

    NARCIS (Netherlands)

    Olieman, N.J.

    2008-01-01

    Robustness of an object is defined as the probability that an object will have properties as required. Robustness Programming (RP) is a mathematical approach for Robustness estimation and Robustness optimisation. An example in the context of designing a food product, is finding the best composition

  3. The Best Performing Cilium: Efficient or Robust?

    CERN Document Server

    Guo, Hanliang

    2015-01-01

    Motile cilia are used by many eukaryotic cells to transport flow. Cilia-driven flows are important to many physiological functions, yet a deep understanding of the interplay between the mechanical structure of cilia and their physiological functions in healthy and diseased conditions remains elusive. For developing such understanding, one needs a quantitative framework for assessing cilia performance and robustness when subject to perturbations in the cilia apparatus. Here, we link cilia design (beating patterns) to function (flow transport) in the context of experimentally- and theoretically-derived cilia models. We particularly examine the optimality and robustness of cilia design. Optimality refers to efficiency of flow transport, while robustness is defined as low sensitivity to variations in the design parameters. We find that suboptimal designs can be more robust than optimal ones. That is, designing for the most efficient cilium does not guarantee robustness. These findings have significant implication...

  4. Specificity of expression of the GUS reporter gene (uidA) driven by the tobacco ASA2 promoter in soybean plants and tissue cultures.

    Science.gov (United States)

    Inaba, Yoshimi; Zhong, Wei Qun; Zhang, Xing-Hai; Widholm, Jack M

    2007-07-01

    Twelve independent lines were transformed by particle bombardment of soybean embryogenic suspension cultures with the tobacco anthranilate synthase (ASA2) promoter driving the uidA (beta-glucuronidase, GUS) reporter gene. ASA2 appears to be expressed in a tissue culture specific manner in tobacco (Song H-S, Brotherton JE, Gonzales RA, Widholm JM. Tissue culture specific expression of a naturally occurring tobacco feedback-insensitive anthranilate synthase. Plant Physiol 1998;117:533-43). The transgenic lines also contained the hygromycin phosphotransferase (hpt) gene and were selected using hygromycin. All the selected cultures or the embryos that were induced from these cultures expressed GUS measured histochemically. However, no histochemical GUS expression could be found in leaves, stems, roots, pods and root nodules of the plants formed from the embryos and their progeny. Pollen from some of the plants and immature and mature seeds and embryogenic cultures initiated from immature cotyledons did show GUS activity. Quantitative 4-methylumbelliferyl-glucuronide (MUG) assays of the GUS activity in various tissues showed that all with observable histochemical GUS activity contained easily measurable activities and leaves and stems that showed no observable histochemical GUS staining did contain very low but measurable MUG activity above that of the untransformed control but orders of magnitude lower than the constitutive 35S-uidA controls used. Low but clearly above background levels of boiling sensitive GUS activity could be observed in the untransformed control immature seeds and embryogenic cultures using the MUG assay. Thus in soybean the ASA2 promoter drives readily observable GUS expression in tissue cultures, pollen and seeds, with only extremely low levels seen in vegetative tissues of the plants. The ASA2 driven expression seen in mature seed was, however, much lower than that seen with the constitutive 35S promoter; less than 2% in seed coats and less than

  5. Robust Schur Stability and Robust H^2 Performance

    DEFF Research Database (Denmark)

    Stoustrup, Jakob; Zhao, K.-Y.

    1996-01-01

    In this paper we address the problems of robust stability androbust QTR H^2 performance for uncertain discrete time systemswith nonlinear parametric uncertainties. We consider two families ofsystems with parametric uncertainties described by state space modelswhich offer a fairly general...... representation of most uncertain systemswith one or two parameters (the approach can be extended to more parameters).For these two families we obtain explicit expressions for the Schurstability radius and for the QTR H^2 robust performance radiusin the case of uncertainties with a single parameter. Moreover, we...

  6. Spatial patterns and light-driven variation of microbial population gene expression in surface waters of the oligotrophic open ocean.

    Science.gov (United States)

    Hewson, Ian; Poretsky, Rachel S; Tripp, H James; Montoya, Joseph P; Zehr, Jonathan P

    2010-07-01

    Because bacterioplankton production rates do not vary strongly across vast expanses of the ocean, it is unclear how variability in community structure corresponds with functional variability in the open ocean. We surveyed community transcript functional profiles at eight locations in the open ocean, in both the light and in the dark, using the genomic subsystems approach, to understand variability in gene expression patterns in surface waters. Metatranscriptomes from geographically distinct areas and collected during the day and night shared a large proportion of metabolic functional similarity (74%) at the finest metabolic resolution possible. The variability between metatranscriptomes could be explained by phylogenetic differences between libraries (Mantel test, P < 0.0001). Several key gene expression pathways, including Photosystem I, Photosystem II and ammonium uptake, demonstrated the most variability both geographically and between light and dark. Libraries were dominated by transcripts of the cyanobacterium Prochlorocococcus marinus, where most geographical and diel variability between metatranscriptomes reflected between-station differences in cyanobacterial phototrophic metabolism. Our results demonstrate that active genetic machinery in surface waters of the ocean is dominated by photosynthetic microorganisms and their site-to-site variability, while variability in the remainder of assemblages is dependent on local taxonomic composition.

  7. The robust regulation problem with robust stability

    NARCIS (Netherlands)

    Cevik, M.K.K.; Schumacher, J.M.

    1999-01-01

    Among the most common purposes of control are the tracking of reference signals and the rejection of disturbance signals in the face of uncertainties. The related design problem is called the `robust regulation problem'. Here we investigate the trade-off between the robust regulation constraint and

  8. Specific expression of short-interfering RNA driven by human telomerase reverse transcriptase promoter in tumor cells

    Institute of Scientific and Technical Information of China (English)

    Xuejing Luan; Limin Guo; Zuozhen Yang; Min Liu; Xin Li; Hua Tang

    2008-01-01

    RNA interference (RNAi) has been shown to be an effective method for inhibiting the expression of a given gene in human cells by targeting with short duplex RNA (short-interfering RNA or siRNA). However, more and more studies suggest that non-specific effects can be induced by siRNAs, such as off-target inhibition, activation of interferon response, and saturation of cellular silencing machinery. It has been known that more than 90% of human tumors exhibit teiomerase activity. Consequently, teiomerase is believed to be a broadspectrum molecular marker of malignancies. In the present study we attempt to develop a tumor-specific RNAi system using the human telomerase reverse transcriptase promoter.This system may provide a basis for RNAi therapy.

  9. Expression of wheat expansin driven by the RD29 promoter in tobacco confers water-stress tolerance without impacting growth and development.

    Science.gov (United States)

    Li, Feng; Han, Yangyang; Feng, Yanan; Xing, Shichao; Zhao, Meirong; Chen, Yanhui; Wang, Wei

    2013-02-10

    Expansins are the key regulators of cell wall extension during plant growth. Previously, we produced transgenic tobacco plants with increased tolerance to water stress by overexpressing the wheat expansin gene TaEXPB23 driven by the constitutive 35S cauliflower mosaic virus (CaMV) promoter. However, the growth and development of 35S::TaEXPB23 transgenic tobacco plants were altered under normal growth conditions, with a faster growth rate at the seedling stage, earlier flowering and maturation, and a shorter plant height compared to WT. In the current study, we determined that cellular characteristics and carbohydrate metabolism were altered in 35S::TaEXPB23 transgenic tobacco plants. We also generated transgenic Arabidopsis plants using the same vector. The transgenic Arabidopsis plants had the same phenotype as the transgenic tobacco plants, which may have resulted from the altered expression of several flowering-related genes. We then produced TaEXPB23 transgenic tobacco plants using the stress-inducible RD29A promoter. The use of this promoter reduced the negative effects of TaEXPB23 on plant growth and development. The RD29A::TaEXPB23 transgenic tobacco plants had greater tolerance to water stress than WT, as determined by examining physiological and biochemical parameters. Therefore, the use of stress-inducible promoters, such as RD29A, may minimize the negative effects of constitutive transgene expression and improve the water-stress tolerance of plants. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Telomerase reverse transcriptase promoter-driven expression of iodine pump genes for targeted radioiodine therapy of malignant glioma cells

    Institute of Scientific and Technical Information of China (English)

    Jian Tan; Wei Li; Peng Wang

    2011-01-01

    Radioiodine is a routine therapy for differentiated thyroid cancers. Non-thyroid cancers can intake radioiodine after transfection of the human sodium iodide symporter (hNIS) gene. The human telomerase reverse transcriptase (hTERT) promoter, an excellent tumor-specific promoter, has potential value for targeted gene therapy of glioma. We used the hTERT promoter to drive the expression of the hNIS and human thyroid peroxidase (hTPO) gene as a primary step for testing the effects of radioiodine therapy on malignant glioma. The U87 and U251 cells were co-transfected with two adenoviral vectors, in which the hNIS gene had been coupled to the hTERT promoter and the hTPO gene had been coupled to the CMV promoter, respectively. Then, we performed Western blot, 135l intake and efflux assays, and clonogenic assay with cancer cells. We also did 99mTc tumor imaging of nude mice models. After co-transfection with Ad-hTERT-hNIS and Ad-CMV-hTPO, glioma cells showed the 125l intake almost 1.5 times higher than cells transfected with Ad-hTERT-hNIS alone. Western blots revealed bands of approximately 70 kDa and 110 kDa, consistent with the hNIS and hTPO proteins. In clonogenic assay, approximately 90% of co transfected cells were killed, compared to 50% of control cells after incubated with 37 MBq of 131I. These results demonstrated that radioiodine therapy was effective in treating malignant glioma cell lines following induction of tumor-specific iodide intake by the hTERT promoter-directed hNIS expression in vitro. Co transfected hNIS and hTPO genes can result in increased intake and longer retention of radioiodine. Nude mice harboring xenografts transfected with Ad-hTERT-NIS can take 99mTc scans.

  11. Thymosin β10 expression driven by the human TERT promoter induces ovarian cancer-specific apoptosis through ROS production.

    Directory of Open Access Journals (Sweden)

    Young-Chae Kim

    Full Text Available Thymosin β(10 (Tβ(10 regulates actin dynamics as a cytoplasm G-actin sequestering protein. Previously, we have shown that Tβ(10 diminishes tumor growth, angiogenesis, and proliferation by disrupting actin and by inhibiting Ras. However, little is known about its mechanism of action and biological function. In the present study, we establish a new gene therapy model using a genetically modified adenovirus, referred to as Ad.TERT.Tβ(10, that can overexpress the Tβ(10 gene in cancer cells. This was accomplished by replacing the native Tβ(10 gene promoter with the human TERT promoter in Ad.TERT.Tβ(10. We investigated the cancer suppression activity of Tβ(10 and found that Ad.TERT.Tβ(10 strikingly induced cancer-specific expression of Tβ(10 as well as apoptosis in a co-culture model of human primary ovarian cancer cells and normal fibroblasts. Additionally, Ad.TERT.Tβ(10 decreased mitochondrial membrane potential and increased reactive oxygen species (ROS production. These effects were amplified by co-treatment with anticancer drugs, such as paclitaxel and cisplatin. These findings indicate that the rise in ROS production due to actin disruption by Tβ(10 overexpression increases apoptosis of human ovarian cancer cells. Indeed, the cancer-specific overexpression of Tβ(10 by Ad.TERT.Tβ(10 could be a valuable anti-cancer therapeutic for the treatment of ovarian cancer without toxicity to normal cells.

  12. High efficiency of targeted mutagenesis in arabidopsis via meiotic promoter-driven expression of Cas9 endonuclease

    KAUST Repository

    Eid, Ayman

    2016-05-28

    Key message: The use of a meiosis I-specific promoter increased the efficiency of targeted mutagenesis and will facilitate the manipulation of homologous recombination. Abstract: The CRISPR/Cas9 system has been harnessed for targeted engineering of eukaryotic genomes, including plants; however, CRISPR/Cas9 efficiency varies considerably in different plant tissues and species. In Arabidopsis, the generation of homozygous or bi-allelic mutants in the first (T1) generation is inefficient. Here, we used specific promoters to drive the expression of Cas9 during meiosis to maximize the efficiency of recovering heritable mutants in T1 plants. Our data reveal that the use of a promoter active in meiosis I resulted in high-efficiency (28 %) recovery of targeted mutants in the T1 generation. Moreover, this method enabled efficient simultaneous targeting of three genes for mutagenesis. Taken together, our results show that the use of meiosis-specific promoters will improve methods for functional genomic analysis and studying the molecular underpinnings of homologous recombination. © 2016, Springer-Verlag Berlin Heidelberg.

  13. ATP8B1 gene expression is driven by a housekeeping-like promoter independent of bile acids and farnesoid X receptor.

    Directory of Open Access Journals (Sweden)

    Dita Cebecauerová

    Full Text Available BACKGROUND: Mutations in ATP8B1 gene were identified as a cause of low γ-glutamyltranspeptidase cholestasis with variable phenotype, ranging from Progressive Familial Intrahepatic Cholestasis to Benign Recurrent Intrahepatic Cholestasis. However, only the coding region of ATP8B1 has been described. The aim of this research was to explore the regulatory regions, promoter and 5'untranslated region, of the ATP8B1 gene. METHODOLOGY/PRINCIPAL FINDINGS: 5'Rapid Amplification of cDNA Ends using human liver and intestinal tissue was performed to identify the presence of 5' untranslated exons. Expression levels of ATP8B1 transcripts were determined by quantitative reverse-transcription PCR and compared with the non-variable part of ATP8B1. Three putative promoters were examined in vitro using a reporter gene assay and the main promoter was stimulated with chenodeoxycholic acid. Four novel untranslated exons located up to 71 kb upstream of the previously published exon 1 and twelve different splicing variants were found both in the liver and the intestine. Multiple transcription start sites were identified within exon -3 and the proximal promoter upstream of this transcription start site cluster was proven to be an essential regulatory element responsible for 70% of total ATP8B1 transcriptional activity. In vitro analysis demonstrated that the main promoter drives constitutive ATP8B1 gene expression independent of bile acids. CONCLUSIONS/SIGNIFICANCE: The structure of the ATP8B1 gene is complex and the previously published transcription start site is not significant. The basal expression of ATP8B1 is driven by a housekeeping-like promoter located 71 kb upstream of the first protein coding exon.

  14. The proteins of intra-nuclear bodies: a data-driven analysis of sequence, interaction and expression

    Directory of Open Access Journals (Sweden)

    Bodén Mikael

    2010-04-01

    Full Text Available Abstract Background Cajal bodies, nucleoli, PML nuclear bodies, and nuclear speckles are morpohologically distinct intra-nuclear structures that dynamically respond to cellular cues. Such nuclear bodies are hypothesized to play important regulatory roles, e.g. by sequestering and releasing transcription factors in a timely manner. While the nucleolus and nuclear speckles have received more attention experimentally, the PML nuclear body and the Cajal body are still incompletely characterized in terms of their roles and protein complement. Results By collating recent experimentally verified data, we find that almost 1000 proteins in the mouse nuclear proteome are known to associate with one or more of the nuclear bodies. Their gene ontology terms highlight their regulatory roles: splicing is confirmed to be a core activity of speckles and PML nuclear bodies house a range of proteins involved in DNA repair. We train support-vector machines to show that nuclear proteins contain discriminative sequence features that can be used to identify their intra-nuclear body associations. Prediction accuracy is highest for nucleoli and nuclear speckles. The trained models are also used to estimate the full protein complement of each nuclear body. Protein interactions are found primarily to link proteins in the nuclear speckles with proteins from other compartments. Cell cycle expression data provide support for increased activity in nucleoli, nuclear speckles and PML nuclear bodies especially during S and G2 phases. Conclusions The large-scale analysis of the mouse nuclear proteome sheds light on the functional organization of physically embodied intra-nuclear compartments. We observe partial support for the hypothesis that the physical organization of the nucleus mirrors functional modularity. However, we are unable to unambiguously identify proteins' intra-nuclear destination, suggesting that critical drivers behind of intra-nuclear translocation are yet to

  15. MicroRNAs Expression in the Ileal Pouch of Patients with Ulcerative Colitis Is Robustly Up-Regulated and Correlates with Disease Phenotypes

    Science.gov (United States)

    Sherman Horev, Hadas; Elad, Hofit; Baram, Liran; Issakov, Ofer; Tulchinsky, Hagit; Pasmanik-Chor, Metsada; Shomron, Noam; Dotan, Iris

    2016-01-01

    Background Gene expression alterations are associated with disease behavior in inflammatory bowel disease (IBD). microRNAs (miRNAs) are dominant in the regulation of gene expression, and may affect IBD phenotype. Our aim was to assess mucosal miRNA expression in IBD and the correlation with intestinal inflammation. Methods We performed a large-scale analysis of ileal mucosal miRNA. Biopsies were retrieved from patients with ileal Crohn’s disease (CD), unoperated ulcerative colitis (UC) patients, UC patients after pouch surgery, and normal controls (NC). Pouch UC patients were classified as having a normal pouch (NP), chronic pouchitis (CP), and Crohn’s-like disease of the pouch (CLDP). miRNA expression was analyzed by parallel massive (next-generation) sequencing (NGS). Bioinformatics tools were applied for clustering and the detection of potential targets. Results Sixty-one subjects were recruited. The ileum of unoperated UC patients was comparable with NC. There were significant miRNA expression alterations (fold change ≥2, corrected P ≤.05) in NP (n = 6), CP (n = 40) and CLDP (n = 139), but only two expression alterations were noted in CD. More than 90% of the altered miRNAs were up-regulated, and many were predicted to be associated with significantly decreased transcripts. miRNAs alterations were generally clustered with disease phenotypes. Conclusions Ileal inflammation causes increased miRNA expression. miRNA alterations correlate with IBD phenotype, apparently by controlling the down-regulation of specific mRNAs. PMID:27536783

  16. Generation of anti-TLR2 intrabody mediating inhibition of macrophage surface TLR2 expression and TLR2-driven cell activation

    Directory of Open Access Journals (Sweden)

    Lindenmaier Werner

    2010-04-01

    Full Text Available Abstract Background Toll-like receptor (TLR 2 is a component of the innate immune system and senses specific pathogen associated molecular patterns (PAMPs of both microbial and viral origin. Cell activation via TLR2 and other pattern recognition receptors (PRRs contributes to sepsis pathology and chronic inflammation both relying on overamplification of an immune response. Intracellular antibodies expressed and retained inside the endoplasmatic reticulum (ER-intrabodies are applied to block translocation of secreted and cell surface molecules from the ER to the cell surface resulting in functional inhibition of the target protein. Here we describe generation and application of a functional anti-TLR2 ER intrabody (αT2ib which was generated from an antagonistic monoclonal antibody (mAb towards human and murine TLR2 (T2.5 to inhibit the function of TLR2. αT2ib is a scFv fragment comprising the variable domain of the heavy chain and the variable domain of the light chain of mAb T2.5 linked together by a synthetic (Gly4Ser3 amino acid sequence. Results Coexpression of αT2ib and mouse TLR2 in HEK293 cells led to efficient retention and accumulation of TLR2 inside the ER compartment. Co-immunoprecipitation of human TLR2 with αT2ib indicated interaction of αT2ib with its cognate antigen within cells. αT2ib inhibited NF-κB driven reporter gene activation via TLR2 but not through TLR3, TLR4, or TLR9 if coexpressed in HEK293 cells. Co-transfection of human TLR2 with increasing amounts of the expression plasmid encoding αT2ib into HEK293 cells demonstrated high efficiency of the TLR2-αT2ib interaction. The αT2ib open reading frame was integrated into an adenoviral cosmid vector for production of recombinant adenovirus (AdV-αT2ib. Transduction with AdVαT2ib specifically inhibited TLR2 surface expression of murine RAW264.7 and primary macrophages derived from bone marrow (BMM. Furthermore, TLR2 activation dependent TNFα mRNA accumulation, as well

  17. Fc-epsilon-RI, the high affinity IgE-receptor, is robustly expressed in the upper gastrointestinal tract and modulated by mucosal inflammation.

    Directory of Open Access Journals (Sweden)

    Christina Bannert

    Full Text Available BACKGROUND: The role of the high affinity IgE receptor, FcεRI, in IgE-mediated immune responses of the gastrointestinal (GI mucosa is poorly understood. Currently, a detailed characterization of FcεRI expression throughout the human gut is lacking. The aim of this study was to define the expression pattern of FcεRI in the GI tract. METHODS/PRINCIPAL FINDINGS: We compared FcεRI expression in children with gastritis/esophagitis (n = 10, celiac disease (n = 10, inflammatory bowel disease (IBD (n = 9, and normal mucosa (n = 5. The α-subunit of FcεRI (FcεRIα, detected by immunohistochemistry, was found on cells infiltrating the mucosa of the esophagus, the stomach, and the duodenum, but was rarely detected in more distal sections of the GI tract. Accordingly, quantitative RT-PCR analysis on esophagus, stomach, duodenum, colon, and rectum biopsies revealed that FcεRIα and -β expression levels decreased towards the distal intestine. mRNA transcripts of the common Fc-receptor-γ chain were present in the entire GI mucosa. Double-immunofluorescence staining of esophageal specimens confirmed that FcεRIα was expressed on intraepithelial mast cells and Langerhans cells. The mRNA expression levels of the α, β, and γ subunits of FcεRI did not correlate with total serum IgE but were associated with mucosal inflammation. CONCLUSION/SIGNIFICANCE: Our data define the upper GI tract as the main site for IgE-mediated immune activation via FcεRI. Tissue mRNA levels of FcεRIα are regulated by inflammatory conditions rather than serum IgE, indicating that FcεRI might also play a role in pathologies other than allergy.

  18. A novel engineering tool in the Bacillus subtilis toolbox: inducer-free activation of gene expression by selection-driven promoter decryptification.

    Science.gov (United States)

    Dormeyer, Miriam; Egelkamp, Richard; Thiele, Martin J; Hammer, Elke; Gunka, Katrin; Stannek, Lorena; Völker, Uwe; Commichau, Fabian M

    2015-02-01

    Bacillus subtilis is a Gram-positive bacterium that is easy to manipulate genetically. Several methods for genome engineering have been developed that helped to extend our understanding of how the B. subtilis cell operates. Consequently, the bacterium has become one of the best-studied organisms. B. subtilis has also been engineered for industrial applications. Moreover, great progress has been achieved in promoter engineering to improve the performance of production strains. To expand the toolbox for engineering B. subtilis, we have constructed a system for the inducer-free activation of gene expression. The system relies on spontaneous mutational activation of a cryptic promoter and selection-driven enrichment of bacteria harbouring the mutated promoter. The synthetic promoter is cryptic due to a perfect direct repeat, separating the binding motifs of the RNA polymerase housekeeping sigma factor. The promoter can be fused to genes for industrial applications and to a growth-promoting gene that, upon mutational activation of the promoter, allows enrichment of the engineered bacteria due to a selective growth advantage.

  19. Viral driven epigenetic events alter the expression of cancer-related genes in Epstein-Barr-virus naturally infected Burkitt lymphoma cell lines.

    Science.gov (United States)

    Hernandez-Vargas, Hector; Gruffat, Henri; Cros, Marie Pierre; Diederichs, Audrey; Sirand, Cécilia; Vargas-Ayala, Romina C; Jay, Antonin; Durand, Geoffroy; Le Calvez-Kelm, Florence; Herceg, Zdenko; Manet, Evelyne; Wild, Christopher P; Tommasino, Massimo; Accardi, Rosita

    2017-07-19

    Epstein-Barr virus (EBV) was identified as the first human virus to be associated with a human malignancy, Burkitt's lymphoma (BL), a pediatric cancer endemic in sub-Saharan Africa. The exact mechanism of how EBV contributes to the process of lymphomagenesis is not fully understood. Recent studies have highlighted a genetic difference between endemic (EBV+) and sporadic (EBV-) BL, with the endemic variant showing a lower somatic mutation load, which suggests the involvement of an alternative virally-driven process of transformation in the pathogenesis of endemic BL. We tested the hypothesis that a global change in DNA methylation may be induced by infection with EBV, possibly thereby accounting for the lower mutation load observed in endemic BL. Our comparative analysis of the methylation profiles of a panel of BL derived cell lines, naturally infected or not with EBV, revealed that the presence of the virus is associated with a specific pattern of DNA methylation resulting in altered expression of cellular genes with a known or potential role in lymphomagenesis. These included ID3, a gene often found to be mutated in sporadic BL. In summary this study provides evidence that EBV may contribute to the pathogenesis of BL through an epigenetic mechanism.

  20. HSD17B1 expression enhances estrogen signaling stimulated by the low active estrone, evidenced by an estrogen responsive element-driven reporter gene in vivo.

    Science.gov (United States)

    Järvensivu, Päivi; Saloniemi-Heinonen, Taija; Awosanya, Michael; Koskimies, Pasi; Saarinen, Niina; Poutanen, Matti

    2015-06-05

    Hydroxysteroid (17beta) dehydrogenase 1 (HSD17B1) belongs to a family of short-chain-dehydrogenases. The enzyme utilizes NAD(P) and NAD(P)H as cofactors, and catalyzes the reversible reaction between estrone (E1) and estradiol (E2) in vitro. Of these steroids, E1 presents with lower estrogenic activity, but is converted to highly active E2 by HSD17B1. HSD17B1 is expressed especially in tissues with a high E2-producing capacity such as human ovaries and placenta, but also in several peripheral estrogen target tissues in humans, and inhibiting the enzyme activity is, thus, considered a promising approach to treat estrogen-dependent diseases. By analyzing transgenic mice universally expressing human HSD17B1 and carrying estrogen-response element (ERE)-driven luciferase reporter gene (Bi-transgenic ERELuc-HSD17B1TG mice) we showed a markedly higher reporter gene activity in various peripheral tissues of these mice as compared with ERELuc mice, indicating enhanced estrogen response generated by human HSD17B1 expression. An increased response after E1 administration was also evident in the Bi-TG mice, indicated by the increased uterus growth response and by the higher ERELuc reporter gene activity in the uterus. Moreover, a HSD17B1 inhibitor significantly reduced E1-induced increase in the uterus weight and uterine epithelial proliferation in the Bi-TG mice. Also the E1-induced ERELuc activity in the inhibitor-treated uterus was reduced by the HSD17B1 inhibitor in immature mice ex vivo, as well as in the liver of adult mice. The data, thus, demonstrate the potential use of the Bi-TG mice as a preclinical in vivo model for screening the efficacy of HSD17B1 inhibitors. As compared with the existing models, the Bi-TG mice present with luciferase activity as an additional, easily quantitative endpoint for the estrogen action.

  1. Robust speaker recognition in noisy environments

    CERN Document Server

    Rao, K Sreenivasa

    2014-01-01

    This book discusses speaker recognition methods to deal with realistic variable noisy environments. The text covers authentication systems for; robust noisy background environments, functions in real time and incorporated in mobile devices. The book focuses on different approaches to enhance the accuracy of speaker recognition in presence of varying background environments. The authors examine: (a) Feature compensation using multiple background models, (b) Feature mapping using data-driven stochastic models, (c) Design of super vector- based GMM-SVM framework for robust speaker recognition, (d) Total variability modeling (i-vectors) in a discriminative framework and (e) Boosting method to fuse evidences from multiple SVM models.

  2. Robust Regression and Lasso

    CERN Document Server

    Xu, Huan; Mannor, Shie

    2008-01-01

    Lasso, or $\\ell^1$ regularized least squares, has been explored extensively for its remarkable sparsity properties. It is shown in this paper that the solution to Lasso, in addition to its sparsity, has robustness properties: it is the solution to a robust optimization problem. This has two important consequences. First, robustness provides a connection of the regularizer to a physical property, namely, protection from noise. This allows a principled selection of the regularizer, and in particular, generalizations of Lasso that also yield convex optimization problems are obtained by considering different uncertainty sets. Secondly, robustness can itself be used as an avenue to exploring different properties of the solution. In particular, it is shown that robustness of the solution explains why the solution is sparse. The analysis as well as the specific results obtained differ from standard sparsity results, providing different geometric intuition. Furthermore, it is shown that the robust optimization formul...

  3. GUS gene expression driven by a citrus promoter in transgenic tobacco and 'Valencia' sweet orange Expressão do gene GUS controlado por promotor de citros em plantas transgênicas de tabaco e laranja 'Valência'

    Directory of Open Access Journals (Sweden)

    Fernando Alves de Azevedo

    2006-11-01

    Full Text Available The objective of this work was the transformation of tobacco and 'Valencia' sweet orange with the GUS gene driven by the citrus phenylalanine ammonia-lyase (PAL gene promoter (CsPP. Transformation was accomplished by co-cultivation of tobacco and 'Valência' sweet orange explants with Agrobacterium tumefaciens containing the binary vector CsPP-GUS/2201. After plant transformation and regeneration, histochemical analyses using GUS staining revealed that CsPP promoter preferentially, but not exclusively, conferred gene expression in xylem tissues of tobacco. Weaker GUS staining was also detected throughout the petiole region in tobacco and citrus CsPP transgenic plants.O objetivo deste trabalho foi realizar a transformação de plantas de tabaco e laranja 'Valência' com o gene GUS controlado pelo promotor do gene da fenilalanina amônia-liase (PAL de citros (CsPP. Foi realizada transformação genética por meio do co-cultivo de explantes de tabaco e laranja 'Valência' com Agrobacterium tumefaciens que continha o vetor binário CsPP-GUS/2201. Após a transformação e a regeneração, a detecção da atividade de GUS por ensaios histoquímicos revelou que o promotor CsPP, preferencialmente, mas não exclusivamente, confere expressão gênica em tecidos do xilema de tabaco. Expressão mais baixa de GUS também foi detectada na região de tecido de pecíolo, em plantas transgênicas (CsPP de tabaco e laranja 'Valência'.

  4. Robust and low cost uniform (15)N-labeling of proteins expressed in Drosophila S2 cells and Spodoptera frugiperda Sf9 cells for NMR applications.

    Science.gov (United States)

    Meola, Annalisa; Deville, Célia; Jeffers, Scott A; Guardado-Calvo, Pablo; Vasiliauskaite, Ieva; Sizun, Christina; Girard-Blanc, Christine; Malosse, Christian; van Heijenoort, Carine; Chamot-Rooke, Julia; Krey, Thomas; Guittet, Eric; Pêtres, Stéphane; Rey, Félix A; Bontems, François

    2014-10-01

    Nuclear magnetic resonance spectroscopy is a powerful tool to study structural and functional properties of proteins, provided that they can be enriched in stable isotopes such as (15)N, (13)C and (2)H. This is usually easy and inexpensive when the proteins are expressed in Escherichiacoli, but many eukaryotic (human in particular) proteins cannot be produced this way. An alternative is to express them in insect cells. Labeled insect cell growth media are commercially available but at prohibitive prices, limiting the NMR studies to only a subset of biologically important proteins. Non-commercial solutions from academic institutions have been proposed, but none of them is really satisfying. We have developed a (15)N-labeling procedure based on the use of a commercial medium depleted of all amino acids and supplemented with a (15)N-labeled yeast autolysate for a total cost about five times lower than that of the currently available solutions. We have applied our procedure to the production of a non-polymerizable mutant of actin in Sf9 cells and of fragments of eukaryotic and viral membrane fusion proteins in S2 cells, which typically cannot be produced in E. coli, with production yields comparable to those obtained with standard commercial media. Our results support, in particular, the putative limits of a self-folding domain within a viral glycoprotein of unknown structure.

  5. Robust Geometric Spanners

    CERN Document Server

    Bose, Prosenjit; Morin, Pat; Smid, Michiel

    2012-01-01

    Highly connected and yet sparse graphs (such as expanders or graphs of high treewidth) are fundamental, widely applicable and extensively studied combinatorial objects. We initiate the study of such highly connected graphs that are, in addition, geometric spanners. We define a property of spanners called robustness. Informally, when one removes a few vertices from a robust spanner, this harms only a small number of other vertices. We show that robust spanners must have a superlinear number of edges, even in one dimension. On the positive side, we give constructions, for any dimension, of robust spanners with a near-linear number of edges.

  6. Robustness of Structural Systems

    DEFF Research Database (Denmark)

    Canisius, T.D.G.; Sørensen, John Dalsgaard; Baker, J.W.

    2007-01-01

    The importance of robustness as a property of structural systems has been recognised following several structural failures, such as that at Ronan Point in 1968,where the consequenceswere deemed unacceptable relative to the initiating damage. A variety of research efforts in the past decades have...... systems. Guidance is provided regarding the assessment of robustness in a framework that considers potential hazards to the system, vulnerability of system components, and failure consequences. Several proposed methods for quantifying robustness are reviewed, and guidelines for robust design...

  7. An Exon-Specific U1snRNA Induces a Robust Factor IX Activity in Mice Expressing Multiple Human FIX Splicing Mutants

    Directory of Open Access Journals (Sweden)

    Dario Balestra

    2016-01-01

    Full Text Available In cellular models we have demonstrated that a unique U1snRNA targeting an intronic region downstream of a defective exon (Exon-specific U1snRNA, ExSpeU1 can rescue multiple exon-skipping mutations, a relevant cause of genetic disease. Here, we explored in mice the ExSpeU1 U1fix9 toward two model Hemophilia B-causing mutations at the 5′ (c.519A > G or 3′ (c.392-8T > G splice sites of F9 exon 5. Hydrodynamic injection of wt-BALB/C mice with plasmids expressing the wt and mutant (hFIX-2G5′ss and hFIX-8G3′ss splicing-competent human factor IX (hFIX cassettes resulted in the expression of hFIX transcripts lacking exon 5 in liver, and in low plasma levels of inactive hFIX. Coinjection of U1fix9, but not of U1wt, restored exon inclusion of variants and in the intrinsically weak FIXwt context. This resulted in appreciable circulating hFIX levels (mean ± SD; hFIX-2G5′ss, 1.0 ± 0.5 µg/ml; hFIX-8G3′ss, 1.2 ± 0.3 µg/ml; and hFIXwt, 1.9 ± 0.6 µg/ml, leading to a striking shortening (from ≃100 seconds of untreated mice to ≃80 seconds of FIX-dependent coagulation times, indicating a hFIX with normal specific activity. This is the first proof-of-concept in vivo that a unique ExSpeU1 can efficiently rescue gene expression impaired by distinct exon-skipping variants, which extends the applicability of ExSpeU1s to panels of mutations and thus cohort of patients.

  8. Direct selection on genetic robustness revealed in the yeast transcriptome.

    Directory of Open Access Journals (Sweden)

    Stephen R Proulx

    Full Text Available BACKGROUND: Evolutionary theory predicts that organisms should evolve the ability to produce high fitness phenotypes in the face of environmental disturbances (environmental robustness or genetic mutations (genetic robustness. While several studies have uncovered mechanisms that lead to both environmental and genetic robustness, we have yet to understand why some components of the genome are more robust than others. According to evolutionary theory, environmental and genetic robustness will have different responses to selective forces. Selection on environmental robustness for a trait is expected to be strong and related to the fitness costs of altering that trait. In contrast to environmental robustness, selection on genetic robustness for a trait is expected to be largely independent of the fitness cost of altering the trait and instead should correlate with the standing genetic variation for the trait that can potentially be buffered. Several mechanisms that provide both environmental and genetic robustness have been described, and this correlation could be explained by direct selection on both forms of robustness (direct selection hypothesis, or through selection on environmental robustness and a correlated response in genetic robustness (congruence hypothesis. METHODOLOGY/PRINCIPAL FINDINGS: Using both published and novel data on gene expression in the yeast Saccharomyces cerevisiae, we find that genetic robustness is correlated with environmental robustness across the yeast genome as predicted by the congruence hypothesis. However, we also show that environmental robustness, but not genetic robustness, is related to per-gene fitness effects. In contrast, genetic robustness is significantly correlated with network position, suggesting that genetic robustness has been under direct selection. CONCLUSIONS/SIGNIFICANCE: We observed a significant correlation between our measures of genetic and environmental robustness, in agreement with the

  9. A Bregman-proximal point algorithm for robust non-negative matrix factorization with possible missing values and outliers - application to gene expression analysis.

    Science.gov (United States)

    Chrétien, Stéphane; Guyeux, Christophe; Conesa, Bastien; Delage-Mouroux, Régis; Jouvenot, Michèle; Huetz, Philippe; Descôtes, Françoise

    2016-08-31

    Non-Negative Matrix factorization has become an essential tool for feature extraction in a wide spectrum of applications. In the present work, our objective is to extend the applicability of the method to the case of missing and/or corrupted data due to outliers. An essential property for missing data imputation and detection of outliers is that the uncorrupted data matrix is low rank, i.e. has only a small number of degrees of freedom. We devise a new version of the Bregman proximal idea which preserves nonnegativity and mix it with the Augmented Lagrangian approach for simultaneous reconstruction of the features of interest and detection of the outliers using a sparsity promoting ℓ 1 penality. An application to the analysis of gene expression data of patients with bladder cancer is finally proposed.

  10. Mechanisms for Robust Cognition

    Science.gov (United States)

    Walsh, Matthew M.; Gluck, Kevin A.

    2015-01-01

    To function well in an unpredictable environment using unreliable components, a system must have a high degree of robustness. Robustness is fundamental to biological systems and is an objective in the design of engineered systems such as airplane engines and buildings. Cognitive systems, like biological and engineered systems, exist within…

  11. Mechanisms for Robust Cognition

    Science.gov (United States)

    Walsh, Matthew M.; Gluck, Kevin A.

    2015-01-01

    To function well in an unpredictable environment using unreliable components, a system must have a high degree of robustness. Robustness is fundamental to biological systems and is an objective in the design of engineered systems such as airplane engines and buildings. Cognitive systems, like biological and engineered systems, exist within…

  12. Robustness of networks

    NARCIS (Netherlands)

    Wang, H.

    2009-01-01

    Our society depends more strongly than ever on large networks such as transportation networks, the Internet and power grids. Engineers are confronted with fundamental questions such as “how to evaluate the robustness of networks for a given service?”, “how to design a robust network?”, because netwo

  13. Robustness from flexibility in the fungal circadian clock

    Directory of Open Access Journals (Sweden)

    Akman Ozgur E

    2010-06-01

    Full Text Available Abstract Background Robustness is a central property of living systems, enabling function to be maintained against environmental perturbations. A key challenge is to identify the structures in biological circuits that confer system-level properties such as robustness. Circadian clocks allow organisms to adapt to the predictable changes of the 24-hour day/night cycle by generating endogenous rhythms that can be entrained to the external cycle. In all organisms, the clock circuits typically comprise multiple interlocked feedback loops controlling the rhythmic expression of key genes. Previously, we showed that such architectures increase the flexibility of the clock's rhythmic behaviour. We now test the relationship between flexibility and robustness, using a mathematical model of the circuit controlling conidiation in the fungus Neurospora crassa. Results The circuit modelled in this work consists of a central negative feedback loop, in which the frequency (frq gene inhibits its transcriptional activator white collar-1 (wc-1, interlocked with a positive feedback loop in which FRQ protein upregulates WC-1 production. Importantly, our model reproduces the observed entrainment of this circuit under light/dark cycles with varying photoperiod and cycle duration. Our simulations show that whilst the level of frq mRNA is driven directly by the light input, the falling phase of FRQ protein, a molecular correlate of conidiation, maintains a constant phase that is uncoupled from the times of dawn and dusk. The model predicts the behaviour of mutants that uncouple WC-1 production from FRQ's positive feedback, and shows that the positive loop enhances the buffering of conidiation phase against seasonal photoperiod changes. This property is quantified using Kitano's measure for the overall robustness of a regulated system output. Further analysis demonstrates that this functional robustness is a consequence of the greater evolutionary flexibility conferred on

  14. Correcting for intra-experiment variation in Illumina BeadChip data is necessary to generate robust gene-expression profiles

    Directory of Open Access Journals (Sweden)

    van Hemert Jano I

    2010-02-01

    Full Text Available Abstract Background Microarray technology is a popular means of producing whole genome transcriptional profiles, however high cost and scarcity of mRNA has led many studies to be conducted based on the analysis of single samples. We exploit the design of the Illumina platform, specifically multiple arrays on each chip, to evaluate intra-experiment technical variation using repeated hybridisations of universal human reference RNA (UHRR and duplicate hybridisations of primary breast tumour samples from a clinical study. Results A clear batch-specific bias was detected in the measured expressions of both the UHRR and clinical samples. This bias was found to persist following standard microarray normalisation techniques. However, when mean-centering or empirical Bayes batch-correction methods (ComBat were applied to the data, inter-batch variation in the UHRR and clinical samples were greatly reduced. Correlation between replicate UHRR samples improved by two orders of magnitude following batch-correction using ComBat (ranging from 0.9833-0.9991 to 0.9997-0.9999 and increased the consistency of the gene-lists from the duplicate clinical samples, from 11.6% in quantile normalised data to 66.4% in batch-corrected data. The use of UHRR as an inter-batch calibrator provided a small additional benefit when used in conjunction with ComBat, further increasing the agreement between the two gene-lists, up to 74.1%. Conclusion In the interests of practicalities and cost, these results suggest that single samples can generate reliable data, but only after careful compensation for technical bias in the experiment. We recommend that investigators appreciate the propensity for such variation in the design stages of a microarray experiment and that the use of suitable correction methods become routine during the statistical analysis of the data.

  15. Robustness of Structures

    DEFF Research Database (Denmark)

    Faber, M.H.; Vrouwenvelder, A.C.W.M.; Sørensen, John Dalsgaard

    2011-01-01

    In 2005, the Joint Committee on Structural Safety (JCSS) together with Working Commission (WC) 1 of the International Association of Bridge and Structural Engineering (IABSE) organized a workshop on robustness of structures. Two important decisions resulted from this workshop, namely the developm......In 2005, the Joint Committee on Structural Safety (JCSS) together with Working Commission (WC) 1 of the International Association of Bridge and Structural Engineering (IABSE) organized a workshop on robustness of structures. Two important decisions resulted from this workshop, namely...... the development of a joint European project on structural robustness under the COST (European Cooperation in Science and Technology) programme and the decision to develop a more elaborate document on structural robustness in collaboration between experts from the JCSS and the IABSE. Accordingly, a project titled...... ‘COST TU0601: Robustness of Structures’ was initiated in February 2007, aiming to provide a platform for exchanging and promoting research in the area of structural robustness and to provide a basic framework, together with methods, strategies and guidelines enhancing robustness of structures...

  16. Robust control of a spatially distributed commercial fishery

    OpenAIRE

    William A. Brock; Xepapadeas, Anastasios; Yannacopoulos, Athanasios N.

    2013-01-01

    We consider a robust control model for a spatially distributed commercial fishery under uncertainty, and in particular a tracking problem, i.e. the problem of robust stabilization of a chosen deterministic benchmark state in the presence of model uncertainty. The problem is expressed in the form of a stochastic linear quadratic robust optimal control problem, which is solved analytically. We focus on the emergence of breakdown from the robust stabilization policy, called hot spots, and commen...

  17. Robust expression of the human neonatal Fc receptor in a truncated soluble form and as a full-length membrane-bound protein in fusion with eGFP.

    Directory of Open Access Journals (Sweden)

    Johan Seijsing

    Full Text Available Studies on the neonatal Fc receptor (FcRn have revealed a multitude of important functions in mammals, including protection of IgG and serum albumin (SA from lysosomal degradation. The pharmacokinetic behavior of therapeutic antibodies, IgG-Fc- and SA-containing drugs is therefore influenced by their interaction with FcRn. Pre-clinical development of such drugs is facilitated if their interaction with FcRn can be studied in vitro. For this reason we have developed a robust system for production of the soluble extracellular domain of human FcRn as well as the full-length receptor as fusion to green fluorescent protein, taking advantage of a lentivirus-based gene delivery system where stable over-expressing cells are easily and rapidly generated. Production of the extracellular domain in multiple-layered culture flasks, followed by affinity purification using immobilized IgG, resulted in capture of milligram amounts of soluble receptor per liter cell culture with retained IgG binding. The receptor was further characterized by SDS-PAGE, western blotting, circular dichroism spectroscopy, ELISA, surface plasmon resonance and a temperature stability assay showing a functional and stable protein of high purity. The full-length receptor was found to be successfully over-expressed in a membrane-bound form with retained pH-dependent IgG- and SA-binding.

  18. MULTIDISCIPLINARY ROBUST OPTIMIZATION DESIGN

    Institute of Scientific and Technical Information of China (English)

    Chen Jianjiang; Xiao Renbin; Zhong Yifang; Dou Gang

    2005-01-01

    Because uncertainty factors inevitably exist under multidisciplinary design environment, a hierarchical multidisciplinary robust optimization design based on response surface is proposed. The method constructs optimization model of subsystem level and system level to coordinate the coupling among subsystems, and also the response surface based on the artificial neural network is introduced to provide information for system level optimization tool to maintain the independence of subsystems,i.e. to realize multidisciplinary parallel design. The application case of electrical packaging demonstrates that reasonable robust optimum solution can be yielded and it is a potential and efficient multidisciplinary robust optimization approach.

  19. Robustness Beamforming Algorithms

    Directory of Open Access Journals (Sweden)

    Sajad Dehghani

    2014-04-01

    Full Text Available Adaptive beamforming methods are known to degrade in the presence of steering vector and covariance matrix uncertinity. In this paper, a new approach is presented to robust adaptive minimum variance distortionless response beamforming make robust against both uncertainties in steering vector and covariance matrix. This method minimize a optimization problem that contains a quadratic objective function and a quadratic constraint. The optimization problem is nonconvex but is converted to a convex optimization problem in this paper. It is solved by the interior-point method and optimum weight vector to robust beamforming is achieved.

  20. Robustness Beamforming Algorithms

    Directory of Open Access Journals (Sweden)

    Sajad Dehghani

    2014-09-01

    Full Text Available Adaptive beamforming methods are known to degrade in the presence of steering vector and covariance matrix uncertinity. In this paper, a new approach is presented to robust adaptive minimum variance distortionless response beamforming make robust against both uncertainties in steering vector and covariance matrix. This method minimize a optimization problem that contains a quadratic objective function and a quadratic constraint. The optimization problem is nonconvex but is converted to a convex optimization problem in this paper. It is solved by the interior-point method and optimum weight vector to robust beamforming is achieved.

  1. Robust Non-Frontal Face Alignment with Edge Based Texture

    Institute of Scientific and Technical Information of China (English)

    Hua Li; Shui-Cheng Yan; Li-Zhong Peng

    2005-01-01

    This paper proposes a new algorithm, called Edge-based Texture Driven Shape Model (E-TDSM), for nonfrontal face alignment task. First, the texture is defined as the un-warped edge image contained in the shape rectangle; then,a Bayesian network is constructed to describe the relationship between the shape and texture models; finally, ExpectationMaximization (EM) approach is utilized to infer the optimal texture and position parameters from the observed shape and texture information. Compared with the traditional shape localization algorithms, E-TDSM has the following advantages:1) the un-warped edge-based texture can better predict the shape and is more robust to the illumination and expression variation than the conventional warped gray-level based texture; 2) the presented Bayesian network indicates the logic structure of the face alignment task; and 3) the mutually enhanced shape and texture observations are integrated to infer the optimal parameters of the proposed Bayesian network using EM approach. The extensive experiments on non-frontal face alignment task demonstrate the effectiveness and robustness of the proposed E-TDSM algorithm.

  2. Adaptively robust filtering with classified adaptive factors

    Institute of Scientific and Technical Information of China (English)

    CUI Xianqiang; YANG Yuanxi

    2006-01-01

    The key problems in applying the adaptively robust filtering to navigation are to establish an equivalent weight matrix for the measurements and a suitable adaptive factor for balancing the contributions of the measurements and the predicted state information to the state parameter estimates. In this paper, an adaptively robust filtering with classified adaptive factors was proposed, based on the principles of the adaptively robust filtering and bi-factor robust estimation for correlated observations. According to the constant velocity model of Kalman filtering, the state parameter vector was divided into two groups, namely position and velocity. The estimator of the adaptively robust filtering with classified adaptive factors was derived, and the calculation expressions of the classified adaptive factors were presented. Test results show that the adaptively robust filtering with classified adaptive factors is not only robust in controlling the measurement outliers and the kinematic state disturbing but also reasonable in balancing the contributions of the predicted position and velocity, respectively, and its filtering accuracy is superior to the adaptively robust filter with single adaptive factor based on the discrepancy of the predicted position or the predicted velocity.

  3. A robust data-driven approach for gene ontology annotation

    OpenAIRE

    2014-01-01

    Gene ontology (GO) and GO annotation are important resources for biological information management and knowledge discovery, but the speed of manual annotation became a major bottleneck of database curation. BioCreative IV GO annotation task aims to evaluate the performance of system that automatically assigns GO terms to genes based on the narrative sentences in biomedical literature. This article presents our work in this task as well as the experimental results after the competition. For th...

  4. Robust Real-Time Musculoskeletal Modeling driven by Electromyograms

    NARCIS (Netherlands)

    Durandau, Guillaume; Farina, Dario; Sartori, Massimo

    2017-01-01

    Objective: Current clinical biomechanics involves lengthy data acquisition and time-consuming offline analyses and current biomechanical models cannot be used for real-time control in man-machine interfaces. We developed a method that enables online analysis of neuromusculoskeletal function in vivo

  5. Robustness of Structures

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard

    2008-01-01

    . According to Danish design rules robustness shall be documented for all structures in high consequence class. The design procedure to document sufficient robustness consists of: 1) Review of loads and possible failure modes / scenarios and determination of acceptable collapse extent; 2) Review......This paper describes the background of the robustness requirements implemented in the Danish Code of Practice for Safety of Structures and in the Danish National Annex to the Eurocode 0, see (DS-INF 146, 2003), (DS 409, 2006), (EN 1990 DK NA, 2007) and (Sørensen and Christensen, 2006). More...... frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure combined with increased requirements to efficiency in design and execution followed by increased risk of human errors has made the need of requirements to robustness of new structures essential...

  6. Robustness - theoretical framework

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Rizzuto, Enrico; Faber, Michael H.

    2010-01-01

    More frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure combined with increased requirements to efficiency in design and execution followed by increased risk of human errors has made the need of requirements to robustness of new struct...... of this fact sheet is to describe a theoretical and risk based framework to form the basis for quantification of robustness and for pre-normative guidelines....

  7. Robust Nonstationary Regression

    OpenAIRE

    1993-01-01

    This paper provides a robust statistical approach to nonstationary time series regression and inference. Fully modified extensions of traditional robust statistical procedures are developed which allow for endogeneities in the nonstationary regressors and serial dependence in the shocks that drive the regressors and the errors that appear in the equation being estimated. The suggested estimators involve semiparametric corrections to accommodate these possibilities and they belong to the same ...

  8. Robustness - theoretical framework

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Rizzuto, Enrico; Faber, Michael H.

    2010-01-01

    More frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure combined with increased requirements to efficiency in design and execution followed by increased risk of human errors has made the need of requirements to robustness of new struct...... of this fact sheet is to describe a theoretical and risk based framework to form the basis for quantification of robustness and for pre-normative guidelines....

  9. Qualitative Robustness in Estimation

    Directory of Open Access Journals (Sweden)

    Mohammed Nasser

    2012-07-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Times New Roman","serif";} Qualitative robustness, influence function, and breakdown point are three main concepts to judge an estimator from the viewpoint of robust estimation. It is important as well as interesting to study relation among them. This article attempts to present the concept of qualitative robustness as forwarded by first proponents and its later development. It illustrates intricacies of qualitative robustness and its relation with consistency, and also tries to remove commonly believed misunderstandings about relation between influence function and qualitative robustness citing some examples from literature and providing a new counter-example. At the end it places a useful finite and a simulated version of   qualitative robustness index (QRI. In order to assess the performance of the proposed measures, we have compared fifteen estimators of correlation coefficient using simulated as well as real data sets.

  10. Robust Protection against Highly Virulent Foot-and-Mouth Disease Virus in Swine by Combination Treatment with Recombinant Adenoviruses Expressing Porcine Alpha and Gamma Interferons and Multiple Small Interfering RNAs.

    Science.gov (United States)

    Kim, Su-Mi; Park, Jong-Hyeon; Lee, Kwang-Nyeong; Kim, Se-Kyung; You, Su-Hwa; Kim, Taeseong; Tark, Dongseob; Lee, Hyang-Sim; Seo, Min-Goo; Kim, Byounghan

    2015-08-01

    Because the currently available vaccines against foot-and-mouth disease (FMD) provide no protection until 4 to 7 days postvaccination, the only alternative method to halt the spread of the FMD virus (FMDV) during outbreaks is the application of antiviral agents. Combination treatment strategies have been used to enhance the efficacy of antiviral agents, and such strategies may be advantageous in overcoming viral mechanisms of resistance to antiviral treatments. We have developed recombinant adenoviruses (Ads) for the simultaneous expression of porcine alpha and gamma interferons (Ad-porcine IFN-αγ) as well as 3 small interfering RNAs (Ad-3siRNA) targeting FMDV mRNAs encoding nonstructural proteins. The antiviral effects of Ad-porcine IFN-αγ and Ad-3siRNA expression were tested in combination in porcine cells, suckling mice, and swine. We observed enhanced antiviral effects in porcine cells and mice as well as robust protection against the highly pathogenic strain O/Andong/SKR/2010 and increased expression of cytokines in swine following combination treatment. In addition, we showed that combination treatment was effective against all serotypes of FMDV. Therefore, we suggest that the combined treatment with Ad-porcine IFN-αγ and Ad-3siRNA may offer fast-acting antiviral protection and be used with a vaccine during the period that the vaccine does not provide protection against FMD. The use of current foot-and-mouth disease (FMD) vaccines to induce rapid protection provides limited effectiveness because the protection does not become effective until a minimum of 4 days after vaccination. Therefore, during outbreaks antiviral agents remain the only available treatment to confer rapid protection and reduce the spread of foot-and-mouth disease virus (FMDV) in livestock until vaccine-induced protective immunity can become effective. Interferons (IFNs) and small interfering RNAs (siRNAs) have been reported to be effective antiviral agents against FMDV, although the

  11. Epistemically Robust Strategy Subsets

    Directory of Open Access Journals (Sweden)

    Geir B. Asheim

    2016-11-01

    Full Text Available We define a concept of epistemic robustness in the context of an epistemic model of a finite normal-form game where a player type corresponds to a belief over the profiles of opponent strategies and types. A Cartesian product X of pure-strategy subsets is epistemically robust if there is a Cartesian product Y of player type subsets with X as the associated set of best reply profiles such that the set Y i contains all player types that believe with sufficient probability that the others are of types in Y − i and play best replies. This robustness concept provides epistemic foundations for set-valued generalizations of strict Nash equilibrium, applicable also to games without strict Nash equilibria. We relate our concept to closedness under rational behavior and thus to strategic stability and to the best reply property and thus to rationalizability.

  12. Robustness in econometrics

    CERN Document Server

    Sriboonchitta, Songsak; Huynh, Van-Nam

    2017-01-01

    This book presents recent research on robustness in econometrics. Robust data processing techniques – i.e., techniques that yield results minimally affected by outliers – and their applications to real-life economic and financial situations are the main focus of this book. The book also discusses applications of more traditional statistical techniques to econometric problems. Econometrics is a branch of economics that uses mathematical (especially statistical) methods to analyze economic systems, to forecast economic and financial dynamics, and to develop strategies for achieving desirable economic performance. In day-by-day data, we often encounter outliers that do not reflect the long-term economic trends, e.g., unexpected and abrupt fluctuations. As such, it is important to develop robust data processing techniques that can accommodate these fluctuations.

  13. Robustness of Spatial Micronetworks

    CERN Document Server

    McAndrew, Thomas C; Bagrow, James P

    2015-01-01

    Power lines, roadways, pipelines and other physical infrastructure are critical to modern society. These structures may be viewed as spatial networks where geographic distances play a role in the functionality and construction cost of links. Traditionally, studies of network robustness have primarily considered the connectedness of large, random networks. Yet for spatial infrastructure physical distances must also play a role in network robustness. Understanding the robustness of small spatial networks is particularly important with the increasing interest in microgrids, small-area distributed power grids that are well suited to using renewable energy resources. We study the random failures of links in small networks where functionality depends on both spatial distance and topological connectedness. By introducing a percolation model where the failure of each link is proportional to its spatial length, we find that, when failures depend on spatial distances, networks are more fragile than expected. Accounting...

  14. Robust Manufacturing Control

    CERN Document Server

    2013-01-01

    This contributed volume collects research papers, presented at the CIRP Sponsored Conference Robust Manufacturing Control: Innovative and Interdisciplinary Approaches for Global Networks (RoMaC 2012, Jacobs University, Bremen, Germany, June 18th-20th 2012). These research papers present the latest developments and new ideas focusing on robust manufacturing control for global networks. Today, Global Production Networks (i.e. the nexus of interconnected material and information flows through which products and services are manufactured, assembled and distributed) are confronted with and expected to adapt to: sudden and unpredictable large-scale changes of important parameters which are occurring more and more frequently, event propagation in networks with high degree of interconnectivity which leads to unforeseen fluctuations, and non-equilibrium states which increasingly characterize daily business. These multi-scale changes deeply influence logistic target achievement and call for robust planning and control ...

  15. Robustness - acceptance criteria

    DEFF Research Database (Denmark)

    Rizzuto, Enrico; Sørensen, John Dalsgaard; Kroon, Inger B.

    2010-01-01

    This factsheet describes the general framework on the bases of which acceptance criteria for requirements on the robustness of structures can be set. Such framework is based on the more general concept of risk-based assessment of engineering systems. The present factsheet is to be seen in conjunc......This factsheet describes the general framework on the bases of which acceptance criteria for requirements on the robustness of structures can be set. Such framework is based on the more general concept of risk-based assessment of engineering systems. The present factsheet is to be seen...... in conjunction with the one on the theoretical framework for robustness (Sørensen et al. 2009). In the present factsheet, the focus is on normative implications....

  16. Robust global motion estimation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A global motion estimation method based on robust statistics is presented in this paper. By using tracked feature points instead of whole image pixels to estimate parameters the process speeds up. To further speed up the process and avoid numerical instability, an alterative description of the problem is given, and three types of solution to the problem are compared. By using a two step process, the robustness of the estimator is also improved. Automatic initial value selection is an advantage of this method. The proposed approach is illustrated by a set of examples, which shows good results with high speed.

  17. Complexity, Robustness, and Performance

    NARCIS (Netherlands)

    B. Visser (Bauke)

    2002-01-01

    textabstractThis paper analyses the relationship between organizational complexity ( the degree of detail of information necessary to correctly assign agents to positions), robustness (the relative loss of performance due to mis-allocated agents), and performance. More complex structures are not

  18. Robustness via Diffractal Architectures

    CERN Document Server

    Moocarme, Matthew

    2015-01-01

    When plane waves diffract through fractal-patterned apertures, the resulting far-field profiles or diffractals also exhibit iterated, self-similar features. Here we show that this specific architecture enables robust signal processing and spatial multiplexing: arbitrary parts of a diffractal contain sufficient information to recreate the entire original sparse signal.

  19. Robustness of structures

    DEFF Research Database (Denmark)

    Vrouwenvelder, T.; Sørensen, John Dalsgaard

    2009-01-01

    robustness is still an issue of controversy and poses difficulties in regard to interpretation as well as regulation. Typically modern structural design codes require that ‘the consequence of damages to structures should not be disproportional to the causes of the damages'. However, despite the importance...

  20. Robustness Envelopes of Networks

    NARCIS (Netherlands)

    Trajanovski, S.; Martín-Hernández, J.; Winterbach, W.; Van Mieghem, P.

    2013-01-01

    We study the robustness of networks under node removal, considering random node failure, as well as targeted node attacks based on network centrality measures. Whilst both of these have been studied in the literature, existing approaches tend to study random failure in terms of average-case behavior

  1. Complexity, Robustness, and Performance

    NARCIS (Netherlands)

    B. Visser (Bauke)

    2002-01-01

    textabstractThis paper analyses the relationship between organizational complexity ( the degree of detail of information necessary to correctly assign agents to positions), robustness (the relative loss of performance due to mis-allocated agents), and performance. More complex structures are not nec

  2. Robust and Adaptive Control With Aerospace Applications

    CERN Document Server

    Lavretsky, Eugene

    2013-01-01

    Robust and Adaptive Control shows the reader how to produce consistent and accurate controllers that operate in the presence of uncertainties and unforeseen events. Driven by aerospace applications the focus of the book is primarily on continuous-dynamical systems.  The text is a three-part treatment, beginning with robust and optimal linear control methods and moving on to a self-contained presentation of the design and analysis of model reference adaptive control (MRAC) for nonlinear uncertain dynamical systems. Recent extensions and modifications to MRAC design are included, as are guidelines for combining robust optimal and MRAC controllers. Features of the text include: ·         case studies that demonstrate the benefits of robust and adaptive control for piloted, autonomous and experimental aerial platforms; ·         detailed background material for each chapter to motivate theoretical developments; ·         realistic examples and simulation data illustrating key features ...

  3. Expression

    Directory of Open Access Journals (Sweden)

    Wang-Xia Wang

    2014-02-01

    Full Text Available The miR-15/107 family comprises a group of 10 paralogous microRNAs (miRNAs, sharing a 5′ AGCAGC sequence. These miRNAs have overlapping targets. In order to characterize the expression of miR-15/107 family miRNAs, we employed customized TaqMan Low-Density micro-fluid PCR-array to investigate the expression of miR-15/107 family members, and other selected miRNAs, in 11 human tissues obtained at autopsy including the cerebral cortex, frontal cortex, primary visual cortex, thalamus, heart, lung, liver, kidney, spleen, stomach and skeletal muscle. miR-103, miR-195 and miR-497 were expressed at similar levels across various tissues, whereas miR-107 is enriched in brain samples. We also examined the expression patterns of evolutionarily conserved miR-15/107 miRNAs in three distinct primary rat brain cell preparations (enriched for cortical neurons, astrocytes and microglia, respectively. In primary cultures of rat brain cells, several members of the miR-15/107 family are enriched in neurons compared to other cell types in the central nervous system (CNS. In addition to mature miRNAs, we also examined the expression of precursors (pri-miRNAs. Our data suggested a generally poor correlation between the expression of mature miRNAs and their precursors. In summary, we provide a detailed study of the tissue and cell type-specific expression profile of this highly expressed and phylogenetically conserved family of miRNA genes.

  4. Comparing dependent robust correlations.

    Science.gov (United States)

    Wilcox, Rand R

    2016-11-01

    Let r1 and r2 be two dependent estimates of Pearson's correlation. There is a substantial literature on testing H0  : ρ1  = ρ2 , the hypothesis that the population correlation coefficients are equal. However, it is well known that Pearson's correlation is not robust. Even a single outlier can have a substantial impact on Pearson's correlation, resulting in a misleading understanding about the strength of the association among the bulk of the points. A way of mitigating this concern is to use a correlation coefficient that guards against outliers, many of which have been proposed. But apparently there are no results on how to compare dependent robust correlation coefficients when there is heteroscedasicity. Extant results suggest that a basic percentile bootstrap will perform reasonably well. This paper reports simulation results indicating the extent to which this is true when using Spearman's rho, a Winsorized correlation or a skipped correlation.

  5. A robust classic.

    Science.gov (United States)

    Kutzner, Florian; Vogel, Tobias; Freytag, Peter; Fiedler, Klaus

    2011-01-01

    In the present research, we argue for the robustness of illusory correlations (ICs, Hamilton & Gifford, 1976) regarding two boundary conditions suggested in previous research. First, we argue that ICs are maintained under extended experience. Using simulations, we derive conflicting predictions. Whereas noise-based accounts predict ICs to be maintained (Fielder, 2000; Smith, 1991), a prominent account based on discrepancy-reducing feedback learning predicts ICs to disappear (Van Rooy et al., 2003). An experiment involving 320 observations with majority and minority members supports the claim that ICs are maintained. Second, we show that actively using the stereotype to make predictions that are met with reward and punishment does not eliminate the bias. In addition, participants' operant reactions afford a novel online measure of ICs. In sum, our findings highlight the robustness of ICs that can be explained as a result of unbiased but noisy learning.

  6. Robust Adaptive Control.

    Science.gov (United States)

    1985-09-19

    13.2 3.6. 14.0. 1.8. 11111.52 *.6 L 3 n1 i erated ~~~m nc. AFOSR-TR- 798 s AD-A 161 349 ROBUST ADAPTIVE CONTROL * FINAL REPORT PREPARED BY: R~ OBERT L... Centre Block Computes the Norm of the [1I] Solo, V., "Time Series Recursions and Stochastc Regressors. The Rematning Elemerts Imple- Approximation

  7. Robust verification analysis

    Energy Technology Data Exchange (ETDEWEB)

    Rider, William, E-mail: wjrider@sandia.gov [Sandia National Laboratories, Center for Computing Research, Albuquerque, NM 87185 (United States); Witkowski, Walt [Sandia National Laboratories, Verification and Validation, Uncertainty Quantification, Credibility Processes Department, Engineering Sciences Center, Albuquerque, NM 87185 (United States); Kamm, James R. [Los Alamos National Laboratory, Methods and Algorithms Group, Computational Physics Division, Los Alamos, NM 87545 (United States); Wildey, Tim [Sandia National Laboratories, Center for Computing Research, Albuquerque, NM 87185 (United States)

    2016-02-15

    We introduce a new methodology for inferring the accuracy of computational simulations through the practice of solution verification. We demonstrate this methodology on examples from computational heat transfer, fluid dynamics and radiation transport. Our methodology is suited to both well- and ill-behaved sequences of simulations. Our approach to the analysis of these sequences of simulations incorporates expert judgment into the process directly via a flexible optimization framework, and the application of robust statistics. The expert judgment is systematically applied as constraints to the analysis, and together with the robust statistics guards against over-emphasis on anomalous analysis results. We have named our methodology Robust Verification. Our methodology is based on utilizing multiple constrained optimization problems to solve the verification model in a manner that varies the analysis' underlying assumptions. Constraints applied in the analysis can include expert judgment regarding convergence rates (bounds and expectations) as well as bounding values for physical quantities (e.g., positivity of energy or density). This approach then produces a number of error models, which are then analyzed through robust statistical techniques (median instead of mean statistics). This provides self-contained, data and expert informed error estimation including uncertainties for both the solution itself and order of convergence. Our method produces high quality results for the well-behaved cases relatively consistent with existing practice. The methodology can also produce reliable results for ill-behaved circumstances predicated on appropriate expert judgment. We demonstrate the method and compare the results with standard approaches used for both code and solution verification on well-behaved and ill-behaved simulations.

  8. Robust Self Tuning Controllers

    DEFF Research Database (Denmark)

    Poulsen, Niels Kjølstad

    1985-01-01

    The present thesis concerns robustness properties of adaptive controllers. It is addressed to methods for robustifying self tuning controllers with respect to abrupt changes in the plant parameters. In the thesis an algorithm for estimating abruptly changing parameters is presented. The estimator...... has several operation modes and a detector for controlling the mode. A special self tuning controller has been developed to regulate plant with changing time delay....

  9. Robustness of Interdependent Networks

    Science.gov (United States)

    Havlin, Shlomo

    2011-03-01

    In interdependent networks, when nodes in one network fail, they cause dependent nodes in other networks to also fail. This may happen recursively and can lead to a cascade of failures. In fact, a failure of a very small fraction of nodes in one network may lead to the complete fragmentation of a system of many interdependent networks. We will present a framework for understanding the robustness of interacting networks subject to such cascading failures and provide a basic analytic approach that may be useful in future studies. We present exact analytical solutions for the critical fraction of nodes that upon removal will lead to a failure cascade and to a complete fragmentation of two interdependent networks in a first order transition. Surprisingly, analyzing complex systems as a set of interdependent networks may alter a basic assumption that network theory has relied on: while for a single network a broader degree distribution of the network nodes results in the network being more robust to random failures, for interdependent networks, the broader the distribution is, the more vulnerable the networks become to random failure. We also show that reducing the coupling between the networks leads to a change from a first order percolation phase transition to a second order percolation transition at a critical point. These findings pose a significant challenge to the future design of robust networks that need to consider the unique properties of interdependent networks.

  10. The Crane Robust Control

    Directory of Open Access Journals (Sweden)

    Marek Hicar

    2004-01-01

    Full Text Available The article is about a control design for complete structure of the crane: crab, bridge and crane uplift.The most important unknown parameters for simulations are burden weight and length of hanging rope. We will use robustcontrol for crab and bridge control to ensure adaptivity for burden weight and rope length. Robust control will be designed for current control of the crab and bridge, necessary is to know the range of unknown parameters. Whole robust will be splitto subintervals and after correct identification of unknown parameters the most suitable robust controllers will be chosen.The most important condition at the crab and bridge motion is avoiding from burden swinging in the final position. Crab and bridge drive is designed by asynchronous motor fed from frequency converter. We will use crane uplift with burden weightobserver in combination for uplift, crab and bridge drive with cooperation of their parameters: burden weight, rope length and crab and bridge position. Controllers are designed by state control method. We will use preferably a disturbance observerwhich will identify burden weight as a disturbance. The system will be working in both modes at empty hook as well asat maximum load: burden uplifting and dropping down.

  11. Co-receptor choice by V alpha14i NKT cells is driven by Th-POK expression rather than avoidance of CD8-mediated negative selection.

    Science.gov (United States)

    Engel, Isaac; Hammond, Kirsten; Sullivan, Barbara A; He, Xi; Taniuchi, Ichiro; Kappes, Dietmar; Kronenberg, Mitchell

    2010-05-10

    Mouse natural killer T (NKT) cells with an invariant V alpha14-J alpha18 rearrangement (V alpha14 invariant [V alpha14i] NKT cells) are either CD4(+)CD8(-) or CD4(-)CD8(-). Because transgenic mice with forced CD8 expression in all T cells exhibited a profound NKT cell deficit, the absence of CD8 has been attributed to negative selection. We now present evidence that CD8 does not serve as a coreceptor for CD1d recognition and that the defect in development in CD8 transgene homozygous mice is the result of a reduction in secondary T cell receptor alpha rearrangements. Thymocytes from mice hemizygous for the CD8 transgene have a less severe rearrangement defect and have functional CD8(+) V alpha14i NKT cells. Furthermore, we demonstrate that the transcription factor Th, Poxviruses and Zinc finger, and Krüppel family (Th-POK) is expressed by V alpha14i NKT cells throughout their differentiation and is necessary both to silence CD8 expression and for the functional maturity of V alpha14i NKT cells. We therefore suggest that Th-POK expression is required for the normal development of V alpha14i NKT cells and that the absence of CD8 expression by these cells is a by-product of such expression, as opposed to the result of negative selection of CD8-expressing V alpha14i NKT cells.

  12. Pulsed Power Driven Fusion Energy

    Energy Technology Data Exchange (ETDEWEB)

    SLUTZ,STEPHEN A.

    1999-11-22

    Pulsed power is a robust and inexpensive technology for obtaining high powers. Considerable progress has been made on developing light ion beams as a means of transporting this power to inertial fusion capsules. However, further progress is hampered by the lack of an adequate ion source. Alternatively, z-pinches can efficiently convert pulsed power into thermal radiation, which can be used to drive an inertial fusion capsule. However, a z-pinch driven fusion explosion will destroy a portion of the transmission line that delivers the electrical power to the z-pinch. They investigate several options for providing standoff for z-pinch driven fusion. Recyclable Transmission Lines (RTLs) appear to be the most promising approach.

  13. Fuzzy Design Method of Product Quality Robustness

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In order to express information on the quality grade of product, designed, the target value of product quality design was described with a fuzzy number in this paper. The rule of robust design with a fuzzy target was analyzed with fuzzy probability theory,then the principle and modeling method of fuzzy robust design for a high quality product were put forward. With this new method used, the high-quality ratio of the product de-signed could be increased, and the ability to resist the influence of various disturbing fac-tors ang noise factors could be enhanced.

  14. Expression of fission yeast cdc25 driven by the wheat ADP-glucose pyrophosphorylase large subunit promoter reduces pollen viability and prevents transmission of the transgene in wheat.

    Science.gov (United States)

    Chrimes, D; Rogers, H J; Francis, D; Jones, H D; Ainsworth, C

    2005-04-01

    Cell number was to be measured in wheat (Triticum aestivum) endosperm expressing Spcdc25 (a fission yeast cell-cycle regulator) controlled by a supposedly endosperm-specific promoter, AGP2 (from the large subunit of ADP glucose pyrophosphorylase). Wheat was transformed by biolistics either with AGP2::GUS or AGP2::Spcdc25. PCR and RT-PCR checked integration and expression of the transgene, respectively. In cv. Chinese Spring, AGP2::GUS was unexpectedly expressed in carpels and pollen, as well as endosperm. In cv. Cadenza, three AGP2::Spcdc25 plants, AGP2::Spcdc25.1, .2 and .3, were generated. Spcdc25 expression was detected in mature leaves of AGP2::Spcdc25.1/.3 which exhibited abnormal spikes, 50% pollen viability and low seed set per plant; both were small compared with the nonexpressing and normal AGP2::Spcdc25.2. Spcdc25 was not transmitted to the T(1) in AGP2::Spcdc25.1 or .3, which developed normally. Spcdc25 was PCR-positive in AGP2::Spcdc25.2, using primers for a central portion, but not with primers for the 5' end, of the ORF, indicating a rearrangement; Spcdc25 was not expressed in either T(0) or T(1). The AGP2 promoter is not tissue-specific and Spcdc25 expression disrupted reproduction.

  15. Study of the essentiality of the Aspergillus fumigatus triA gene, encoding RNA triphosphatase, using the heterokaryon rescue technique and the conditional gene expression driven by the alcA and niiA promoters.

    Science.gov (United States)

    Monteiro, M Cândida; De Lucas, J Ramón

    2010-01-01

    The identification of essential genes represents a critical step in the discovery of novel therapeutic targets in Aspergillus fumigatus. Structural analyses of the Saccharomyces cerevisiae RNA triphosphatase pointed out this enzyme as an attractive therapeutic target for fungal infections. In addition, demonstration of the essentiality of the S. cerevisiae RNA triphosphatase encoding gene enhanced the value of this potential therapeutic target. Nevertheless, consideration of a fungal RNA triphosphatase as an ideal therapeutic target needs confirmation of the essentiality of the respective gene in a fungal pathogen. In this work, we analyzed the essentiality of the A. fumigatus triA gene, encoding RNA triphosphatase, by conditional gene expression and heterokaryon deletion. Using the conditional gene expression driven by the alcA promoter (alcA(P)), we found that TriA depletion causes morphological abnormalities that result in a very strong growth inhibition. Nevertheless, since a strict terminal phenotype was not observed, the essentiality of the triA gene could not be ensured. Accordingly, the essentiality of this gene was analyzed by the heterokaryon rescue technique. Results obtained unequivocally demonstrated the essentiality of the A. fumigatus triA gene, indicating the suitability of the RNA triphosphatase as an ideal therapeutic target to treat A. fumigatus infections. Besides, a second conditional gene expression system, based on the niiA promoter (niiA(P)), was utilized in this work. Although the niiA(P)-mediated repression of triA was less severe than that driven by the alcA(P), a strong growth inhibition was also found in niiA(P)-triA strains. Finally, E-tests performed to determine whether triA down-regulated cells became more sensitive to antifungals suggest a synergic effect between amphotericin B and another antifungal inhibiting the A. fumigatus RNA triphosphatase activity.

  16. Robust Kriged Kalman Filtering

    Energy Technology Data Exchange (ETDEWEB)

    Baingana, Brian; Dall' Anese, Emiliano; Mateos, Gonzalo; Giannakis, Georgios B.

    2015-11-11

    Although the kriged Kalman filter (KKF) has well-documented merits for prediction of spatial-temporal processes, its performance degrades in the presence of outliers due to anomalous events, or measurement equipment failures. This paper proposes a robust KKF model that explicitly accounts for presence of measurement outliers. Exploiting outlier sparsity, a novel l1-regularized estimator that jointly predicts the spatial-temporal process at unmonitored locations, while identifying measurement outliers is put forth. Numerical tests are conducted on a synthetic Internet protocol (IP) network, and real transformer load data. Test results corroborate the effectiveness of the novel estimator in joint spatial prediction and outlier identification.

  17. PGE2-driven expression of c-Myc and oncomiR-17-92 contributes to apoptosis resistance in NSCLC.

    Science.gov (United States)

    Krysan, Kostyantyn; Kusko, Rebecca; Grogan, Tristan; O'Hearn, James; Reckamp, Karen L; Walser, Tonya C; Garon, Edward B; Lenburg, Marc E; Sharma, Sherven; Spira, Avrum E; Elashoff, David; Dubinett, Steven M

    2014-05-01

    Aberrant expression of microRNAs (miRNA) with oncogenic capacities (oncomiRs) has been described for several different malignancies. The first identified oncomiR, miR-17-92, is frequently overexpressed in a variety of cancers and its targets include the tumor suppressor PTEN. The transcription factor c-Myc (MYC) plays a central role in proliferative control and is rapidly upregulated upon mitogenic stimulation. Expression of c-Myc is frequently deregulated in tumors, facilitating proliferation and inhibiting terminal differentiation. The c-Myc-regulated network comprises a large number of transcripts, including those encoding miRNAs. Here, prostaglandin E2 (PGE2) exposure rapidly upregulates the expression of the MYC gene followed by the elevation of miR-17-92 levels, which in turn suppresses PTEN expression, thus enhancing apoptosis resistance in non-small cell lung cancer (NSCLC) cells. Knockdown of MYC expression or the miR-17-92 cluster effectively reverses this outcome. Similarly, miR-17-92 levels are significantly elevated in NSCLC cells ectopically expressing COX-2. Importantly, circulating miR-17-92 was elevated in the blood of patients with lung cancer as compared with subjects at risk for developing lung cancer. Furthermore, in patients treated with celecoxib, miR-17-92 levels were significantly reduced. These data demonstrate that PGE2, abundantly produced by NSCLC and inflammatory cells in the tumor microenvironment, is able to stimulate cell proliferation and promote resistance to pharmacologically induced apoptosis in a c-Myc and miR-17-92-dependent manner. This study describes a novel mechanism, involving c-Myc and miR-17-92, which integrates cell proliferation and apoptosis resistance. ©2014 AACR.

  18. Robustness Metrics: Consolidating the multiple approaches to quantify Robustness

    DEFF Research Database (Denmark)

    Göhler, Simon Moritz; Eifler, Tobias; Howard, Thomas J.

    2016-01-01

    determined to be conceptually different from one another. The metrics were classified by their meaning and interpretation based on the types of information necessary to calculate the metrics. Four different classes were identified: 1) Sensitivity robustness metrics; 2) Size of feasible design space...... and to remove the ambiguities of the term robustness. By applying an exemplar metric from each class to a case study, the differences between the classes were further highlighted.These classes form the basis for the definition of four specific sub-definitions of robustness, namely the ‘robust concept’, ‘robust...

  19. Minimax Robustness of Bayesian Forecasting under Functional Distortions of Probability Densities

    OpenAIRE

    Kharin, Alexey

    2002-01-01

    The problems of robustness in Bayesian forecasting are considered under distortions of the hypothetical probability densities. The expressions for the guaranteed upper risk functional are obtained and the robust prediction statistics under certain types of distortions are constructed.

  20. Adaptive Robust Variable Selection

    CERN Document Server

    Fan, Jianqing; Barut, Emre

    2012-01-01

    Heavy-tailed high-dimensional data are commonly encountered in various scientific fields and pose great challenges to modern statistical analysis. A natural procedure to address this problem is to use penalized least absolute deviation (LAD) method with weighted $L_1$-penalty, called weighted robust Lasso (WR-Lasso), in which weights are introduced to ameliorate the bias problem induced by the $L_1$-penalty. In the ultra-high dimensional setting, where the dimensionality can grow exponentially with the sample size, we investigate the model selection oracle property and establish the asymptotic normality of the WR-Lasso. We show that only mild conditions on the model error distribution are needed. Our theoretical results also reveal that adaptive choice of the weight vector is essential for the WR-Lasso to enjoy these nice asymptotic properties. To make the WR-Lasso practically feasible, we propose a two-step procedure, called adaptive robust Lasso (AR-Lasso), in which the weight vector in the second step is c...

  1. Robust Cultural Pluralism

    Directory of Open Access Journals (Sweden)

    Richard A. Shweder

    2013-11-01

    Full Text Available In this wide ranging interview, Professor Richard A. Shweder from the Department of Comparative Human Development at the University of Chicago, discusses whether it is or is not possible to be a robust cultural pluralist and a dedicated political liberal at the same time. In this discussion, Professor Shweder offers his insights - based on over 40 years of research - on issues related to the history and re-emergence of cultural psychology; moral anthropology and psychology; the experimental method in psychological investigation and its philosophical basis; contemporary and historical cultural collisions – most notably conflicting representations of female genital surgeries; cultural diversity and inequality; and the dissemination of ideas through open access publishing and Twitter. Professor Shweder ends by offering valuable advice to young researchers in the field of cultural psychology as well as a glimpse into the larger themes of his forthcoming book, which seeks to provide answers to the question of what forms of political liberalism are most compatible with robust cultural pluralism and which are not.

  2. Increased vitamin D-driven signalling and expression of the vitamin D receptor, MSX2, and RANKL in tooth resorption in cats

    NARCIS (Netherlands)

    Booij-Vrieling, H.E.; Ferbus, D.; Tryfonidou, M.A.; Riemers, F.M.; Penning, L.C.; Berdal, A.; Everts, V.; Hazewinkel, H.A.W.

    2010-01-01

    Tooth resorption occurs in 20-75% of cats (Felis catus). The aetiology is not known, but vitamin D is suggested to be involved. Vitamin D acts through a nuclear receptor (VDR) and increases the expression of receptor activator of nuclear factor-κB ligand (rankl) and muscle segment homeobox 2 (msx2)

  3. New results on robust exponential stability of integral delay systems

    Science.gov (United States)

    Melchor-Aguilar, Daniel

    2016-06-01

    The robust exponential stability of integral delay systems with exponential kernels is investigated. Sufficient delay-dependent robust conditions expressed in terms of linear matrix inequalities and matrix norms are derived by using the Lyapunov-Krasovskii functional approach. The results are combined with a new result on quadratic stabilisability of the state-feedback synthesis problem in order to derive a new linear matrix inequality methodology of designing a robust non-fragile controller for the finite spectrum assignment of input delay systems that guarantees simultaneously a numerically safe implementation and also the robustness to uncertainty in the system matrices and to perturbation in the feedback gain.

  4. μ Synthesis Method for Robust Control of Uncertain Nonlinear Systems

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    μ synthesis method for robust control of uncertain nonlinear systems is propored, which is based on feedback linearization. First, nonlinear systems are linearized as controllable linear systems by I/O linearization,such that uncertain nonlinear systems are expressed as the linear fractional transformations (LFTs) on the generalized linearized plants and uncertainty.Then,linear robust controllers are obtained for the LFTs usingμsynthesis method based on H∞ optimization.Finally,the nonlinear robust controllers are constructed by combining the linear robust controllers and the nonlinear feedback.An example is given to illustrate the design.

  5. A cAMP-independent carbohydrate-driven mechanism inhibits tnaA expression and TnaA enzyme activity in Escherichia coli.

    Science.gov (United States)

    Li, Gang; Young, Kevin D

    2014-09-01

    When Escherichia coli is grown in a medium lacking glucose or another preferred carbohydrate, the concentration of cAMP-cAMP receptor protein (cAMP-CRP) increases, and this latter complex regulates the expression of more than 180 genes. To respond rapidly to changes in carbohydrate availability, E. coli must maintain a suitable intracellular concentration of cAMP by either exporting or degrading excess cAMP. Currently, cAMP export via the TolC protein is thought to be more efficient at reducing these levels than is CpdA-mediated degradation of cAMP. Here, we compared the contributions of TolC and CpdA by measuring the expression of cAMP-regulated genes that encode tryptophanase (TnaA) and β-galactosidase. In the presence of exogenous cAMP, a tolC mutant produced intermediate levels of these enzymes, suggesting that cAMP levels were held in check by CpdA. Conversely, a cpdA mutant produced much higher amounts of these enzymes, indicating that CpdA was more efficient than TolC at reducing cAMP levels. Surprisingly, expression of the tnaA gene halted rapidly when glucose was added to cells lacking both TolC and CpdA, even though under these conditions cAMP could not be removed by either pathway and tnaA expression should have remained high. This result suggests the existence of an additional mechanism that eliminates intracellular cAMP or terminates expression of some cAMP-CRP-regulated genes. In addition, adding glucose and other carbohydrates rapidly inhibited the function of pre-formed TnaA, indicating that TnaA is regulated by a previously unknown carbohydrate-dependent post-translational mechanism.

  6. Gene expression profiling identifies microphthalmia-associated transcription factor (MITF and Dickkopf-1 (DKK1 as regulators of microenvironment-driven alterations in melanoma phenotype.

    Directory of Open Access Journals (Sweden)

    Mariusz L Hartman

    Full Text Available BACKGROUND: The diversity of functional phenotypes observed within a tumor does not exclusively result from intratumoral genetic heterogeneity but also from the response of cancer cells to the microenvironment. We have previously demonstrated that the morphological and functional phenotypes of melanoma can be dynamically altered upon external stimuli. FINDINGS: In the present study, transcriptome profiles were generated to explore the molecules governing phenotypes of melanospheres grown in the bFGF(+EGF(+ serum-free cultures and monolayers maintained in the serum-containing medium. Higher expression levels of MITF-dependent genes that are responsible for differentiation, e.g., TYR and MLANA, and stemness-related genes, e.g., ALDH1A1, were detected in melanospheres. These results were supported by the observation that the melanospheres contained more pigmented cells and cells exerting the self-renewal capacity than the monolayers. In addition, the expression of the anti-apoptotic, MITF-dependent genes e.g., BCL2A1 was also higher in the melanospheres. The enhanced activity of MITF in melanospheres, as illustrated by the increased expression of 74 MITF-dependent genes, identified MITF as a central transcriptional regulator in melanospheres. Importantly, several genes including MITF-dependent ones were expressed in melanospheres and original tumors at similar levels. The reduced MITF level in monolayers might be partially explained by suppression of the Wnt/β-catenin pathway, and DKK1, a secreted inhibitor of this pathway, was highly up-regulated in monolayers in comparison to melanospheres and original tumors. Furthermore, the silencing of DKK1 in monolayers increased the percentage of cells with self-renewing capacity. CONCLUSIONS: Our study indicates that melanospheres can be used to unravel the molecular pathways that sustain intratumoral phenotypic heterogeneity. Melanospheres directly derived from tumor specimens more accurately mirrored

  7. Identification of the avian RBP7 gene as a new adipose-specific gene and RBP7 promoter-driven GFP expression in adipose tissue of transgenic quail.

    Science.gov (United States)

    Ahn, Jinsoo; Shin, Sangsu; Suh, Yeunsu; Park, Ju Yeon; Hwang, Seongsoo; Lee, Kichoon

    2015-01-01

    The discovery of an increasing number of new adipose-specific genes has significantly contributed to our understanding of adipose tissue biology and the etiology of obesity and its related diseases. In the present study, comparison of gene expression profiles among various tissues was performed by analysis of chicken microarray data, leading to identification of RBP7 as a novel adipose-specific gene in chicken. Adipose-specific expression of RBP7 in the avian species was further confirmed at the protein and mRNA levels. Examination of the transcription factor binding sites within the chicken RBP7 promoter by Matinspector software revealed potential binding sites for adipogenic transcription factors. This led to the hypothesis that the RBP7 promoter can be utilized to overexpress a transgene in adipose tissue in order to further investigate the function of a transgene in adipose tissue. Several lines of transgenic quail containing a green fluorescent protein (GFP) gene under the control of the RBP7 promoter were generated using lentivirus-mediated gene transfer. The GFP expression in transgenic quail was specific to adipose tissue and increased after adipocyte differentiation. This expression pattern was consistent with endogenous RBP7 expression, suggesting the RBP7 promoter is sufficient to overexpress a gene of interest in adipose tissue at later developmental stages. These findings will lead to the establishment of a novel RBP7 promoter cassette which can be utilized for overexpressing genes of interest in adipose tissue in vivo to study the function of genes in adipose tissue development and lipid metabolism.

  8. The quantitative genetics of phenotypic robustness.

    Directory of Open Access Journals (Sweden)

    Hunter B Fraser

    Full Text Available Phenotypic robustness, or canalization, has been extensively investigated both experimentally and theoretically. However, it remains unknown to what extent robustness varies between individuals, and whether factors buffering environmental variation also buffer genetic variation. Here we introduce a quantitative genetic approach to these issues, and apply this approach to data from three species. In mice, we find suggestive evidence that for hundreds of gene expression traits, robustness is polymorphic and can be genetically mapped to discrete genomic loci. Moreover, we find that the polymorphisms buffering genetic variation are distinct from those buffering environmental variation. In fact, these two classes have quite distinct mechanistic bases: environmental buffers of gene expression are predominantly sex-specific and trans-acting, whereas genetic buffers are not sex-specific and often cis-acting. Data from studies of morphological and life-history traits in plants and yeast support the distinction between polymorphisms buffering genetic and environmental variation, and further suggest that loci buffering different types of environmental variation do overlap with one another. These preliminary results suggest that naturally occurring polymorphisms affecting phenotypic robustness could be abundant, and that these polymorphisms may generally buffer either genetic or environmental variation, but not both.

  9. Domestication-driven Gossypium profilin 1 (GhPRF1) gene transduces early flowering phenotype in tobacco by spatial alteration of apical/floral-meristem related gene expression.

    Science.gov (United States)

    Pandey, Dhananjay K; Chaudhary, Bhupendra

    2016-05-13

    Plant profilin genes encode core cell-wall structural proteins and are evidenced for their up-regulation under cotton domestication. Notwithstanding striking discoveries in the genetics of cell-wall organization in plants, little is explicit about the manner in which profilin-mediated molecular interplay and corresponding networks are altered, especially during cellular signalling of apical meristem determinacy and flower development. Here we show that the ectopic expression of GhPRF1 gene in tobacco resulted in the hyperactivation of apical meristem and early flowering phenotype with increased flower number in comparison to the control plants. Spatial expression alteration in CLV1, a key meristem-determinacy gene, is induced by the GhPRF1 overexpression in a WUS-dependent manner and mediates cell signalling to promote flowering. But no such expression alterations are recorded in the GhPRF1-RNAi lines. The GhPRF1 transduces key positive flowering regulator AP1 gene via coordinated expression of FT4, SOC1, FLC1 and FT1 genes involved in the apical-to-floral meristem signalling cascade which is consistent with our in silico profilin interaction data. Remarkably, these positive and negative flowering regulators are spatially controlled by the Actin-Related Protein (ARP) genes, specifically ARP4 and ARP6 in proximate association with profilins. This study provides a novel and systematic link between GhPRF1 gene expression and the flower primordium initiation via up-regulation of the ARP genes, and an insight into the functional characterization of GhPRF1 gene acting upstream to the flowering mechanism. Also, the transgenic plants expressing GhPRF1 gene show an increase in the plant height, internode length, leaf size and plant vigor. Overexpression of GhPRF1 gene induced early and increased flowering in tobacco with enhanced plant vigor. During apical meristem determinacy and flower development, the GhPRF1 gene directly influences key flowering regulators through ARP

  10. Model-based robustness testing for avionics-embedded software

    Institute of Scientific and Technical Information of China (English)

    Yang Shunkun; Liu Bin; Wang Shihai; Lu Minyan

    2013-01-01

    Robustness testing for safety-critical embedded software is still a challenge in its nascent stages.In this paper,we propose a practical methodology and implement an environment by employing model-based robustness testing for embedded software systems.It is a system-level black-box testing approach in which the fault behaviors of embedded software is triggered with the aid of modelbased fault injection by the support of an executable model-driven hardware-in-loop (HIL) testing environment.The prototype implementation of the robustness testing environment based on the proposed approach is experimentally discussed and illustrated by industrial case studies based on several avionics-embedded software systems.The results show that our proposed and implemented robustness testing method and environment are effective to find more bugs,and reduce burdens of testing engineers to enhance efficiency of testing tasks,especially for testing complex embedded systems.

  11. International Conference on Robust Statistics

    CERN Document Server

    Filzmoser, Peter; Gather, Ursula; Rousseeuw, Peter

    2003-01-01

    Aspects of Robust Statistics are important in many areas. Based on the International Conference on Robust Statistics 2001 (ICORS 2001) in Vorau, Austria, this volume discusses future directions of the discipline, bringing together leading scientists, experienced researchers and practitioners, as well as younger researchers. The papers cover a multitude of different aspects of Robust Statistics. For instance, the fundamental problem of data summary (weights of evidence) is considered and its robustness properties are studied. Further theoretical subjects include e.g.: robust methods for skewness, time series, longitudinal data, multivariate methods, and tests. Some papers deal with computational aspects and algorithms. Finally, the aspects of application and programming tools complete the volume.

  12. Libration driven multipolar instabilities

    CERN Document Server

    Cébron, David; Herreman, Wietze

    2014-01-01

    We consider rotating flows in non-axisymmetric enclosures that are driven by libration, i.e. by a small periodic modulation of the rotation rate. Thanks to its simplicity, this model is relevant to various contexts, from industrial containers (with small oscillations of the rotation rate) to fluid layers of terrestial planets (with length-of-day variations). Assuming a multipolar $n$-fold boundary deformation, we first obtain the two-dimensional basic flow. We then perform a short-wavelength local stability analysis of the basic flow, showing that an instability may occur in three dimensions. We christen it the Libration Driven Multipolar Instability (LDMI). The growth rates of the LDMI are computed by a Floquet analysis in a systematic way, and compared to analytical expressions obtained by perturbation methods. We then focus on the simplest geometry allowing the LDMI, a librating deformed cylinder. To take into account viscous and confinement effects, we perform a global stability analysis, which shows that...

  13. Activation of stress-activated MAP protein kinases up-regulates expression of transgenes driven by the cytomegalovirus immediate/early promoter.

    OpenAIRE

    Bruening, W; Giasson, B; Mushynski, W; Durham, H D

    1998-01-01

    The immediate/early promoter/enhancer of cytomegalovirus (CMV promoter) is one of the most commonly used promoters for expression of transgenes in eukaryotic cells. In practice, the CMV promoter is often thought of as a constitutively active unregulated promoter. However, we have observed that transcription from the CMV promoter can be up-regulated by a variety of environmental stresses. Many forms of cellular stress stimulate MAP kinase signalling pathways, resulting in activation of stress-...

  14. CX3CR1 is expressed by human B lymphocytes and mediates [corrected] CX3CL1 driven chemotaxis of tonsil centrocytes.

    Directory of Open Access Journals (Sweden)

    Anna Corcione

    Full Text Available BACKGROUND: Fractalkine/CX(3CL1, a surface chemokine, binds to CX(3CR1 expressed by different lymphocyte subsets. Since CX(3CL1 has been detected in the germinal centres of secondary lymphoid tissue, in this study we have investigated CX(3CR1 expression and function in human naïve, germinal centre and memory B cells isolated from tonsil or peripheral blood. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate unambiguously that highly purified human B cells from tonsil and peripheral blood expressed CX(3CR1 at mRNA and protein levels as assessed by quantitative PCR, flow cytometry and competition binding assays. In particular, naïve, germinal centre and memory B cells expressed CX(3CR1 but only germinal centre B cells were attracted by soluble CX(3CL1 in a transwell assay. CX(3CL1 signalling in germinal centre B cells involved PI3K, Erk1/2, p38, and Src phosphorylation, as assessed by Western blot experiments. CX(3CR1(+ germinal centre B cells were devoid of centroblasts and enriched for centrocytes that migrated to soluble CX(3CL1. ELISA assay showed that soluble CX(3CL1 was secreted constitutively by follicular dendritic cells and T follicular helper cells, two cell populations homing in the germinal centre light zone as centrocytes. At variance with that observed in humans, soluble CX(3CL1 did not attract spleen B cells from wild type mice. OVA immunized CX(3CR1(-/- or CX(3CL1(-/- mice showed significantly decreased specific IgG production compared to wild type mice. CONCLUSION/SIGNIFICANCE: We propose a model whereby human follicular dendritic cells and T follicular helper cells release in the light zone of germinal centre soluble CX(3CL1 that attracts centrocytes. The functional implications of these results warrant further investigation.

  15. Robust automated knowledge capture.

    Energy Technology Data Exchange (ETDEWEB)

    Stevens-Adams, Susan Marie; Abbott, Robert G.; Forsythe, James Chris; Trumbo, Michael Christopher Stefan; Haass, Michael Joseph; Hendrickson, Stacey M. Langfitt

    2011-10-01

    This report summarizes research conducted through the Sandia National Laboratories Robust Automated Knowledge Capture Laboratory Directed Research and Development project. The objective of this project was to advance scientific understanding of the influence of individual cognitive attributes on decision making. The project has developed a quantitative model known as RumRunner that has proven effective in predicting the propensity of an individual to shift strategies on the basis of task and experience related parameters. Three separate studies are described which have validated the basic RumRunner model. This work provides a basis for better understanding human decision making in high consequent national security applications, and in particular, the individual characteristics that underlie adaptive thinking.

  16. Passion, Robustness and Perseverance

    DEFF Research Database (Denmark)

    Lim, Miguel Antonio; Lund, Rebecca

    2016-01-01

    Evaluation and merit in the measured university are increasingly based on taken-for-granted assumptions about the “ideal academic”. We suggest that the scholar now needs to show that she is passionate about her work and that she gains pleasure from pursuing her craft. We suggest that passion...... and pleasure achieve an exalted status as something compulsory. The scholar ought to feel passionate about her work and signal that she takes pleasure also in the difficult moments. Passion has become a signal of robustness and perseverance in a job market characterised by funding shortages, increased pressure...... to produce measurable output, and precariousness. For young academics in particular it is increasingly important to demonstrate the “right attitude”, “feelings”, and “personality traits” because they have yet to accumulate a record of past achievements that are used as the basis of merit. In hiring decisions...

  17. Robust procedures in chemometrics

    DEFF Research Database (Denmark)

    Kotwa, Ewelina

    -way chemometrical methods, such as PCA and PARAFAC models for analysing spatial and depth profiles of sea water samples, defined by three data modes: depth, variables and geographical location. Emphasis was also put on predicting fluorescence values, as being a natural measure of biological activity, by applying....... applying a multivariate and multi-way data analytical frame-work in fields where less sophisticated data analysis methods are currently used, and 2. developing new, more robust alternatives to already existing multivariate tools. The first part of the study was realised by applying two- and three...... and comparing the Partial Least Squares (PLS) regression technique with its multi-way alternative, N-PLS. Results of the analysis indicated superiority of the three-way frame-work, potentially constituting a novel assessment of the sea water measurements. Particularly in the case of regression models...

  18. Robust Optical Flow Estimation

    Directory of Open Access Journals (Sweden)

    Javier Sánchez Pérez

    2013-10-01

    Full Text Available n this work, we describe an implementation of the variational method proposed by Brox etal. in 2004, which yields accurate optical flows with low running times. It has several benefitswith respect to the method of Horn and Schunck: it is more robust to the presence of outliers,produces piecewise-smooth flow fields and can cope with constant brightness changes. Thismethod relies on the brightness and gradient constancy assumptions, using the information ofthe image intensities and the image gradients to find correspondences. It also generalizes theuse of continuous L1 functionals, which help mitigate the effect of outliers and create a TotalVariation (TV regularization. Additionally, it introduces a simple temporal regularizationscheme that enforces a continuous temporal coherence of the flow fields.

  19. Validation of community robustness

    CERN Document Server

    Carissimo, Annamaria; Defeis, Italia

    2016-01-01

    The large amount of work on community detection and its applications leaves unaddressed one important question: the statistical validation of the results. In this paper we present a methodology able to clearly detect if the community structure found by some algorithms is statistically significant or is a result of chance, merely due to edge positions in the network. Given a community detection method and a network of interest, our proposal examines the stability of the partition recovered against random perturbations of the original graph structure. To address this issue, we specify a perturbation strategy and a null model to build a set of procedures based on a special measure of clustering distance, namely Variation of Information, using tools set up for functional data analysis. The procedures determine whether the obtained clustering departs significantly from the null model. This strongly supports the robustness against perturbation of the algorithm used to identify the community structure. We show the r...

  20. Unique long non-coding RNA expression signature in ETV6/RUNX1-driven B-cell precursor acute lymphoblastic leukemia.

    Science.gov (United States)

    Ghazavi, Farzaneh; De Moerloose, Barbara; Van Loocke, Wouter; Wallaert, Annelynn; Helsmoortel, Hetty H; Ferster, Alina; Bakkus, Marleen; Plat, Geneviève; Delabesse, Eric; Uyttebroeck, Anne; Van Nieuwerburgh, Filip; Deforce, Dieter; Van Roy, Nadine; Speleman, Frank; Benoit, Yves; Lammens, Tim; Van Vlierberghe, Pieter

    2016-11-08

    Overwhelming evidence indicates that long non-coding RNAs have essential roles in tumorigenesis. Nevertheless, their role in the molecular pathogenesis of pediatric B-cell precursor acute lymphoblastic leukemia has not been extensively explored. Here, we conducted a comprehensive analysis of the long non-coding RNA transcriptome in ETV6/RUNX1-positive BCP-ALL, one of the most frequent subtypes of pediatric leukemia. First, we used primary leukemia patient samples to identify an ETV6/RUNX1 specific expression signature consisting of 596 lncRNA transcripts. Next, integration of this lncRNA signature with RNA sequencing of BCP-ALL cell lines and lncRNA profiling of an in vitro model system of ETV6/RUNX1 knockdown, revealed that lnc-NKX2-3-1, lnc-TIMM21-5, lnc-ASTN1-1 and lnc-RTN4R-1 are truly regulated by the oncogenic fusion protein. Moreover, sustained inactivation of lnc-RTN4R-1 and lnc-NKX2-3-1 in ETV6/RUNX1 positive cells caused profound changes in gene expression. All together, our study defined a unique lncRNA expression signature associated with ETV6/RUNX1-positive BCP-ALL and identified lnc-RTN4R-1 and lnc-NKX2-3-1 as lncRNAs that might be functionally implicated in the biology of this prevalent subtype of human leukemia.

  1. Provably robust digital watermarking

    Science.gov (United States)

    Chen, Brian; Wornell, Gregory W.

    1999-11-01

    Copyright notification and enforcement, authentication, covert communication, and hybrid transmission are examples of emerging multimedia applications for digital watermarking methods, methods for embedding one signal (e.g., the digital watermark) within another 'host' signal to form a third, 'composite' signal. The embedding is designed to achieve efficient trade-offs among the three conflicting goals of maximizing information-embedding rate, minimizing distortion between the host signal and composite signal, and maximizing the robustness of the embedding. Quantization index modulation (QIM) methods are a class of watermarking methods that achieve provably good rate-distortion-robustness performance. Indeed, QIM methods exist that achieve performance within a few dB of capacity in the case of a (possibly colored) Gaussian host signal and an additive (possibly colored) Gaussian noise channel. Also, QIM methods can achieve capacity with a type of postprocessing called distortion compensation. This capacity is independent of host signal statistics, and thus, contrary to popular belief, the information-embedding capacity when the host signal is not available at the decoder is the same as the case when the host signal is available at the decoder. A low-complexity realization of QIM called dither modulation has previously been proven to be better than both linear methods of spread spectrum and nonlinear methods of low-bit(s) modulation against square-error distortion-constrained intentional attacks. We introduce a new form of dither modulation called spread-transform dither modulation that retains these favorable performance characteristics while achieving better performance against other attacks such as JPEG compression.

  2. Tissue specific expression of antifreeze protein and growth hormone transgenes driven by the ocean pout (Macrozoarces americanus) antifreeze protein OP5a gene promoter in Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Hobbs, Rod S; Fletcher, Garth L

    2008-02-01

    Previous research aimed at producing genetically improved salmon broodstock for aquaculture led to the creation of two lines of transgenic Atlantic salmon using gene constructs that were derived in part from the ocean pout OP5a antifreeze protein (AFP) gene. One of the lines was produced using an OP5a AFP gene in which the 5' region of the promoter was removed (termed t-OP5a-AFP), and the other line contains a growth hormone (GH) transgene (EO-1alpha) that consists of a chinook salmon GH cDNA driven by a truncated OP5a AFP promoter that is almost identical to that of the t-OP5a-AFP construct. The similarity of the promoter regions of these transgenes provided an opportunity to evaluate their tissue specific expression patterns. Expression of mRNA was evaluated using Northern blot and RT-PCR techniques. The results demonstrate that the AFP and GH trangenes were expressed in almost all body tissues, suggesting that the promoter region of the OP5a AFP gene lacks tissue specific elements. Northern analysis revealed that expression of the t-OP5a-AFP gene was considerably greater than that of the EO-1alpha GH transgene. Only the spleen tissue of the GH transgenics showed a visible band of hybridization. In contrast clear bands of hybridization were evident in all tissues, except for blood cells, of the AFP transgenics with heart, liver and brain tissue showing the highest levels of mRNA expression. This higher level of expression could be attributable to the presence of introns in the t-OP5a-AFP transgene. Since the GH transgenic salmon grow considerably faster than non-transgenics the low levels of GH transgene expression in this line were clearly sufficient to produce the desired rapid growth phenotype. In contrast the levels of AFP expression were inadequate to impart any improvement in the freeze resistance of the AFP transgenic salmon.

  3. Ischemia-driven angiogenesis.

    Science.gov (United States)

    Dor, Y; Keshet, E

    1997-11-01

    New blood vessels usually develop in places where they are most needed. A prime example of neovascularization representing a positive feedback response to insufficient perfusion is the development of collateral blood vessels in the ischemic myocardium and leg. The recent discoveries of hypoxia-inducible transcription and angiogenic factors have provided important mechanistic links between the metabolic consequences of ischemia and compensatory angiogenesis. Vascular endothelial growth factor (VEGF) has emerged as the key mediator of ischemia-driven angiogenesis. Environmental stresses, including hypoxia, hypoglycemia, and hypoferremia, upregulate VEGF expression at both the transcriptional and posttranscriptional levels. VEGF acts in turn on adjacent vascular beds expressing cognate receptors and induces sprouting and capillary growth toward the ischemic tissue. In addition to expanding the vasculature at sites where existing vessels have been occluded or obliterated, VEGF also functions to match the vascular density according to development and physiologic increases in oxygen consumption. Fine adjustment of the vasculature includes a step of oxygen-regulated vascular pruning mediated by VEGF in its capacity as a survival factor for newly formed vessels. Pathologic settings of ischemia-driven angiogenesis include a major component of stress-induced angiogenesis during tumor neovascularization and abnormal vessel growth associated with retinopathies. The latter represents an excessive angiogenic response to conditions of severe retinal ischemia. Further insights into the mechanism of stress-induced angiogenesis are likely to suggest new ways to augment growth of collateral vessels and to restrain unwarranted neovascularization in tumors and retinopathies. (Trends Cardiovasc Med 1997;7:289-294). © 1997, Elsevier Science Inc.

  4. An Evolutionary Approach for Robust Layout Synthesis of MEMS

    DEFF Research Database (Denmark)

    Fan, Zhun; Wang, Jiachuan; Goodman, Erik

    2005-01-01

    The paper introduces a robust design method for layout synthesis of MEM resonators subject to inherent geometric uncertainties such as the fabrication error on the sidewall of the structure. The robust design problem is formulated as a multi-objective constrained optimisation problem after certain...... assumptions and treated with multiobjective genetic algorithm (MOGA), a special type of evolutionary computing approaches. Case study based on layout synthesis of a comb-driven MEM resonator shows that the approach proposed in this paper can lead to design results that meet the target performance and are less...... sensitive to geometric uncertainties than typical designs...

  5. Robust Nonlinear Neural Codes

    Science.gov (United States)

    Yang, Qianli; Pitkow, Xaq

    2015-03-01

    Most interesting natural sensory stimuli are encoded in the brain in a form that can only be decoded nonlinearly. But despite being a core function of the brain, nonlinear population codes are rarely studied and poorly understood. Interestingly, the few existing models of nonlinear codes are inconsistent with known architectural features of the brain. In particular, these codes have information content that scales with the size of the cortical population, even if that violates the data processing inequality by exceeding the amount of information entering the sensory system. Here we provide a valid theory of nonlinear population codes by generalizing recent work on information-limiting correlations in linear population codes. Although these generalized, nonlinear information-limiting correlations bound the performance of any decoder, they also make decoding more robust to suboptimal computation, allowing many suboptimal decoders to achieve nearly the same efficiency as an optimal decoder. Although these correlations are extremely difficult to measure directly, particularly for nonlinear codes, we provide a simple, practical test by which one can use choice-related activity in small populations of neurons to determine whether decoding is suboptimal or optimal and limited by correlated noise. We conclude by describing an example computation in the vestibular system where this theory applies. QY and XP was supported by a grant from the McNair foundation.

  6. Robust Principal Component Analysis?

    CERN Document Server

    Candes, Emmanuel J; Ma, Yi; Wright, John

    2009-01-01

    This paper is about a curious phenomenon. Suppose we have a data matrix, which is the superposition of a low-rank component and a sparse component. Can we recover each component individually? We prove that under some suitable assumptions, it is possible to recover both the low-rank and the sparse components exactly by solving a very convenient convex program called Principal Component Pursuit; among all feasible decompositions, simply minimize a weighted combination of the nuclear norm and of the L1 norm. This suggests the possibility of a principled approach to robust principal component analysis since our methodology and results assert that one can recover the principal components of a data matrix even though a positive fraction of its entries are arbitrarily corrupted. This extends to the situation where a fraction of the entries are missing as well. We discuss an algorithm for solving this optimization problem, and present applications in the area of video surveillance, where our methodology allows for th...

  7. Robust relativistic bit commitment

    Science.gov (United States)

    Chakraborty, Kaushik; Chailloux, André; Leverrier, Anthony

    2016-12-01

    Relativistic cryptography exploits the fact that no information can travel faster than the speed of light in order to obtain security guarantees that cannot be achieved from the laws of quantum mechanics alone. Recently, Lunghi et al. [Phys. Rev. Lett. 115, 030502 (2015), 10.1103/PhysRevLett.115.030502] presented a bit-commitment scheme where each party uses two agents that exchange classical information in a synchronized fashion, and that is both hiding and binding. A caveat is that the commitment time is intrinsically limited by the spatial configuration of the players, and increasing this time requires the agents to exchange messages during the whole duration of the protocol. While such a solution remains computationally attractive, its practicality is severely limited in realistic settings since all communication must remain perfectly synchronized at all times. In this work, we introduce a robust protocol for relativistic bit commitment that tolerates failures of the classical communication network. This is done by adding a third agent to both parties. Our scheme provides a quadratic improvement in terms of expected sustain time compared with the original protocol, while retaining the same level of security.

  8. Robust correlation tracker

    Indian Academy of Sciences (India)

    M Sankar Kishore; K Veerabhadra Rao

    2001-06-01

    Correlation tracking plays an important role in the automation of weapon systems. Area correlation is an effective technique for tracking targets that have neither prominent features nor high contrast with the background and the ‘target’ can even be an area or a scene of interest. Even though this technique is robust under varying conditions of target background and light conditions, it has some problems like target drift and false registration. When the tracker or target is moving, the registration point drifts due to the discrete pixel size and aspect angle change. In this research work, an attempt has been made to improve the performance of a correlation tracker for tracking ground targets with very poor contrast. In the present work only the CCD visible images with very poor target to background contrast are considered. Applying novel linear and nonlinear filters, the problems present in the correlation tracker are overcome. Confidence and redundancy measures have been proposed to improve the performance by detecting misregistration. The proposed algorithm is tested on different sequences of images and its performance is satisfactory.

  9. Substance P and Calcitonin Gene Related Peptide Mediate Pain in Chronic Pancreatitis and Their Expression is Driven by Nerve Growth Factor

    Science.gov (United States)

    Liu, LianSheng; Shenoy, Mohan; Pasricha, Pankaj Jay

    2014-01-01

    Context Calcitonin gene-related peptide (CGRP), substance P and nerve growth factor play an important role in inflammatory pain in various somatic pain models but their role in chronic pancreatitis has not been well studied. Objectives The aim of this study was to investigate the effects of intrathecal administration of calcitonin gene-related peptide antagonist and substance P receptor antagonist on pain behavior in a rat model of chronic pancreatitis and to determine whether nerve growth factor drives the up-regulation of expression of these neuropeptides in sensory neurons. Methods Pancreatitis was induced by retrograde infusion of trinitobenzene sulfonic acid into the pancreatic duct of adult rats. Three weeks post infusion continuous intrathecal infusion of the calcitonin gene-related peptide antagonist alpha CGRP8-37 or neurokinin-1 receptor antagonist CP-96345 or its inactive enantiomer CP-96344 was administered for seven days. The effects of treatment on pancreatic hyperalgesia were assessed by sensitivity of the abdominal wall to von Frey filament probing as well as by the nocifensive response to electrical stimulation of the pancreas. In a separate experiment chronic pancreatitis was induced and pancreas specific dorsal root ganglion neurons labeled with DiI were assessed for calcitonin gene-related peptide and substance P immunoreactivity. Results Intrathecal infusion of calcitonin gene-related peptide and neurokinin-1 receptor antagonists significantly attenuated behavioral pain responses in rats with chronic pancreatitis. Further, treatment of chronic pancreatitis rats with nerve growth factor antibody significantly reduced pancreas specific neurons expressing calcitonin gene-related peptide and substance P in thoracic dorsal root ganglion. Conclusions Calcitonin gene-related peptide and substance P mediate pancreatic hyperalgesia in chronic pancreatitis and nerve growth factor in turn sustains the up-regulation of these neuropeptides in pancreatic

  10. The Control of Tendon-Driven Dexterous Hands with Joint Simulation

    Directory of Open Access Journals (Sweden)

    Jinbao Chen

    2014-01-01

    Full Text Available An adaptive impedance control algorithm for tendon-driven dexterous hands is presented. The main idea of this algorithm is to compensate the output of the classical impedance control by an offset that is a proportion-integration-differentiation (PID expression of force error. The adaptive impedance control can adjust the impedance parameters indirectly when the environment position and stiffness are uncertain. In addition, the position controller and inverse kinematics solver are specially designed for the tendon-driven hand. The performance of the proposed control algorithm is validated by using MATLAB and ADAMS software for joint simulation. ADAMS is a great software for virtual prototype analysis. A tendon-driven hand model is built and a control module is generated in ADAMS. Then the control system is built in MATLAB using the control module. The joint simulation results demonstrate fast response and robustness of the algorithm when the environment is not exactly known, so the algorithm is suitable for the control of tendon-driven dexterous hands.

  11. Robustness Evaluation of Timber Structures

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Sørensen, John Dalsgaard

    2009-01-01

    The present paper considers robustness evaluation of a Norwegian sports arena with a structural system of glulam frames. The robustness evaluation is based on the framework for robustness analysis introduced in the Danish Code of Practice for the Safety of Structures and a probabilistic modelling...... of the timber material proposed in the Probabilistic Model Code (PMC) of the Joint Committee on Structural Safety (JCSS). The results show that the requirements for robustness of the structure are highly related to the modelling of the snow load used on the structures when ‘removal of a limited part...

  12. Characterization of Optically and Electrically Evoked Dopamine Release in Striatal Slices from Digenic Knock-in Mice with DAT-Driven Expression of Channelrhodopsin

    Science.gov (United States)

    2017-01-01

    Fast-scan cyclic voltammetry (FCV) is an established method to monitor increases in extracellular dopamine (DA) concentration ([DA]o) in the striatum, which is densely innervated by DA axons. Ex vivo brain slice preparations provide an opportunity to identify endogenous modulators of DA release. For these experiments, local electrical stimulation is often used to elicit release of DA, as well as other transmitters, in the striatal microcircuitry; changes in evoked increases in [DA]o after application of a pharmacological agent (e.g., a receptor antagonist) indicate a regulatory role for the transmitter system interrogated. Optogenetic methods that allow specific stimulation of DA axons provide a complementary, bottom-up approach for elucidating factors that regulate DA release. To this end, we have characterized DA release evoked by local electrical and optical stimulation in striatal slices from mice that genetically express a variant of channelrhodopsin-2 (ChR2). Evoked increases in [DA]o in the dorsal and ventral striatum (dStr and vStr) were examined in a cross of a Cre-dependent ChR2 line (“Ai32” mice) with a DAT::Cre mouse line. In dStr, repeated optical pulse-train stimulation at the same recording site resulted in rundown of evoked [DA]o using heterozygous mice, which contrasted with the stability seen with electrical stimulation. Similar rundown was seen in the presence of a nicotinic acetylcholine receptor (nAChR) antagonist, implicating the absence of concurrent nAChR activation in DA release instability in slices. Rundown with optical stimulation in dStr could be circumvented by recording from a population of sites, each stimulated only once. Same-site rundown was less pronounced with single-pulse stimulation, and a stable baseline could be attained. In vStr, stable optically evoked increases in [DA]o at single sites could be achieved using heterozygous mice, although with relatively low peak [DA]o. Low release could be overcome by using mice with a

  13. The secondary structure of the R region of a murine leukemia virus is important for stimulation of long terminal repeat-driven gene expression.

    Science.gov (United States)

    Cupelli, L; Okenquist, S A; Trubetskoy, A; Lenz, J

    1998-10-01

    In addition to their role in reverse transcription, the R-region sequences of some retroviruses affect viral transcription. The first 28 nucleotides of the R region within the long terminal repeat (LTR) of the murine type C retrovirus SL3 were predicted to form a stem-loop structure. We tested whether this structure affected the transcriptional activity of the viral LTR. Mutations that altered either side of the stem and thus disrupted base pairing were generated. These decreased the level of expression of a reporter gene under the control of viral LTR sequences about 5-fold in transient expression assays and 10-fold in cells stably transformed with the LTR-reporter plasmids. We also generated a compensatory mutant in which both the ascending and descending sides of the stem were mutated such that the nucleotide sequence was different but the predicted secondary structure was maintained. Most of the activity of the wild-type SL3 element was restored in this mutant. Thus, the stem-loop structure was important for the maximum activity of the SL3 LTR. Primer extension analysis indicated that the stem-loop structure affected the levels of cytoplasmic RNA. Nuclear run-on assays indicated that deletion of the R region had a small effect on transcriptional initiation and no effect on RNA polymerase processivity. Thus, the main effect of the R-region element was on one or more steps that occurred after the template was transcribed by RNA polymerase. This finding implied that the main function of the R-region element involved RNA processing. R-region sequences of human immunodeficiency virus type 1 or mouse mammary tumor virus could not replace the SL3 element. R-region sequences from an avian reticuloendotheliosis virus partially substituted for the SL3 sequences. R-region sequences from Moloney murine leukemia virus or feline leukemia virus did function in place of the SL3 element. Thus, the R region element appears to be a general feature of the mammalian type C genus of

  14. GATA3-Driven Th2 Responses Inhibit TGF-β1–Induced FOXP3 Expression and the Formation of Regulatory T Cells

    Science.gov (United States)

    Mantel, Pierre-Yves; Kuipers, Harmjan; Boyman, Onur; Rhyner, Claudio; Ouaked, Nadia; Rückert, Beate; Karagiannidis, Christian; Lambrecht, Bart N; Hendriks, Rudolf W; Crameri, Reto; Akdis, Cezmi A; Blaser, Kurt; Schmidt-Weber, Carsten B

    2007-01-01

    Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-β–mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy. PMID:18162042

  15. Neutral Sphingomyelinase (SMPD3) Deficiency Causes a Novel Form of Chondrodysplasia and Dwarfism That Is Rescued by Col2A1-Driven smpd3 Transgene Expression

    Science.gov (United States)

    Stoffel, Wilhelm; Jenke, Britta; Holz, Barbara; Binczek, Erika; Günter, Robert Heinz; Knifka, Jutta; Koebke, Jürgen; Niehoff, Anja

    2007-01-01

    Neutral sphingomyelinase SMPD3 (nSMase2), a sphingomyelin phosphodiesterase, resides in the Golgi apparatus and is ubiquitously expressed. Gene ablation of smpd3 causes a generalized prolongation of the cell cycle that leads to late embryonic and juvenile hypoplasia because of the SMPD3 deficiency in hypothalamic neurosecretory neurons. We show here that this novel form of combined pituitary hormone deficiency is characterized by the perturbation of the hypothalamus-pituitary growth axis, associated with retarded chondrocyte development and enchondral ossification in the epiphyseal growth plate. To study the contribution by combined pituitary hormone deficiency and by the local SMPD3 deficiency in the epiphyseal growth plate to the skeletal phenotype, we introduced the full-length smpd3 cDNA transgene under the control of the chondrocyte-specific promoter Col2a1. A complete rescue of the smpd3−/− mouse from severe short-limbed skeletal dysplasia was achieved. The smpd3−/− mouse shares its dwarf and chondrodysplasia phenotype with the most common form of human achondrodysplasia, linked to the fibroblast-growth-factor receptor 3 locus, not linked to deficits in the hypothalamic-pituitary epiphyseal growth plate axis. The rescue of smpd3 in vivo has implications for future research into dwarfism and, particularly, growth and development of the skeletal system and for current screening and future treatment of combined dwarfism and chondrodysplasia. PMID:17591962

  16. GATA3-driven Th2 responses inhibit TGF-beta1-induced FOXP3 expression and the formation of regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Pierre-Yves Mantel

    2007-12-01

    Full Text Available Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg and inducible Treg (iTreg commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4 present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF-beta-mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.

  17. Evolution of mutational robustness in an RNA virus.

    Directory of Open Access Journals (Sweden)

    Rebecca Montville

    2005-11-01

    Full Text Available Mutational (genetic robustness is phenotypic constancy in the face of mutational changes to the genome. Robustness is critical to the understanding of evolution because phenotypically expressed genetic variation is the fuel of natural selection. Nonetheless, the evidence for adaptive evolution of mutational robustness in biological populations is controversial. Robustness should be selectively favored when mutation rates are high, a common feature of RNA viruses. However, selection for robustness may be relaxed under virus co-infection because complementation between virus genotypes can buffer mutational effects. We therefore hypothesized that selection for genetic robustness in viruses will be weakened with increasing frequency of co-infection. To test this idea, we used populations of RNA phage phi6 that were experimentally evolved at low and high levels of co-infection and subjected lineages of these viruses to mutation accumulation through population bottlenecking. The data demonstrate that viruses evolved under high co-infection show relatively greater mean magnitude and variance in the fitness changes generated by addition of random mutations, confirming our hypothesis that they experience weakened selection for robustness. Our study further suggests that co-infection of host cells may be advantageous to RNA viruses only in the short term. In addition, we observed higher mutation frequencies in the more robust viruses, indicating that evolution of robustness might foster less-accurate genome replication in RNA viruses.

  18. Developer Driven and User Driven Usability Evaluations

    DEFF Research Database (Denmark)

    Bruun, Anders

    2013-01-01

    Usability evaluation provide software development teams with insights on the degree to which a software application enables a user to achieve his/her goals, how fast these goals can be achieved, how easy it is to learn and how satisfactory it is in use Although usability evaluations are crucial....... The four primary findings from my studies are: 1) The developer driven approach reveals a high level of thoroughness and downstream utility. 2) The user driven approach has higher performance regarding validity 3) The level of reliability is comparable between the two approaches. 4) The user driven...

  19. A Robust Design Applicability Model

    DEFF Research Database (Denmark)

    Ebro, Martin; Lars, Krogstie; Howard, Thomas J.

    2015-01-01

    This paper introduces a model for assessing the applicability of Robust Design (RD) in a project or organisation. The intention of the Robust Design Applicability Model (RDAM) is to provide support for decisions by engineering management considering the relevant level of RD activities. The applic...

  20. Robust and distributed hypothesis testing

    CERN Document Server

    Gül, Gökhan

    2017-01-01

    This book generalizes and extends the available theory in robust and decentralized hypothesis testing. In particular, it presents a robust test for modeling errors which is independent from the assumptions that a sufficiently large number of samples is available, and that the distance is the KL-divergence. Here, the distance can be chosen from a much general model, which includes the KL-divergence as a very special case. This is then extended by various means. A minimax robust test that is robust against both outliers as well as modeling errors is presented. Minimax robustness properties of the given tests are also explicitly proven for fixed sample size and sequential probability ratio tests. The theory of robust detection is extended to robust estimation and the theory of robust distributed detection is extended to classes of distributions, which are not necessarily stochastically bounded. It is shown that the quantization functions for the decision rules can also be chosen as non-monotone. Finally, the boo...

  1. A Robust Enough Virtue Epistemology

    DEFF Research Database (Denmark)

    Broncano-Berrocal, Fernando

    2016-01-01

    What is the nature of knowledge? A popular answer to that long-standing question comes from robust virtue epistemology, whose key idea is that knowing is just a matter of succeeding cognitively—i.e., coming to believe a proposition truly—due to an exercise of cognitive ability. Versions of robust...

  2. Robust Understanding of Statistical Variation

    Science.gov (United States)

    Peters, Susan A.

    2011-01-01

    This paper presents a framework that captures the complexity of reasoning about variation in ways that are indicative of robust understanding and describes reasoning as a blend of design, data-centric, and modeling perspectives. Robust understanding is indicated by integrated reasoning about variation within each perspective and across…

  3. Repetitive control of electrically driven robot manipulators

    Science.gov (United States)

    Fateh, Mohammad Mehdi; Ahsani Tehrani, Hojjat; Karbassi, Seyed Mehdi

    2013-04-01

    This article presents a novel robust discrete repetitive control of electrically driven robot manipulators for tracking of a periodic trajectory. We propose a novel model, which presents the highly non-linear dynamics of robot manipulator in the form of linear discrete-time time-varying system. Based on the proposed model, we develop a two-term control law. The first term is an ordinary time-optimal and minimum-norm (TOMN) control by employing parametric controllers to guarantee stability. The second term is a novel robust control to improve the control performance in the face of uncertainties. The robust control estimates and compensates uncertainties including the parametric uncertainty, unmodelled dynamics and external disturbances. Performance of the proposed method is compared with two discrete methods, namely the TOMN control and an adaptive iterative learning (AIL) control. Simulation results confirm superiority of the proposed method in terms of the convergence speed and precision.

  4. Robust statistical methods with R

    CERN Document Server

    Jureckova, Jana

    2005-01-01

    Robust statistical methods were developed to supplement the classical procedures when the data violate classical assumptions. They are ideally suited to applied research across a broad spectrum of study, yet most books on the subject are narrowly focused, overly theoretical, or simply outdated. Robust Statistical Methods with R provides a systematic treatment of robust procedures with an emphasis on practical application.The authors work from underlying mathematical tools to implementation, paying special attention to the computational aspects. They cover the whole range of robust methods, including differentiable statistical functions, distance of measures, influence functions, and asymptotic distributions, in a rigorous yet approachable manner. Highlighting hands-on problem solving, many examples and computational algorithms using the R software supplement the discussion. The book examines the characteristics of robustness, estimators of real parameter, large sample properties, and goodness-of-fit tests. It...

  5. Minimax Robust Quickest Change Detection

    CERN Document Server

    Unnikrishnan, Jayakrishnan; Meyn, Sean

    2009-01-01

    The two popular criteria of optimality for quickest change detection procedures are Lorden's criterion and the Bayesian criterion. In this paper a robust version of these quickest change detection problems is considered when the pre-change and post-change distributions are not known exactly but belong to known uncertainty classes of distributions. For uncertainty classes that satisfy a specific condition, it is shown that one can identify least favorable distributions (LFDs) from the uncertainty classes, such that the detection rule designed for the LFDs is optimal for the robust problem in a minimax sense. The condition is similar to that required for the identification of LFDs for the robust hypothesis testing problem studied by Huber. An upper bound on the delay incurred by the robust test is also obtained in the asymptotic setting under Lorden's criterion of optimality, which quantifies the delay penalty incurred to guarantee robustness. When the LFDs can be identified, the proposed test is easier to impl...

  6. Graph measures and network robustness

    CERN Document Server

    Ellens, W

    2013-01-01

    Network robustness research aims at finding a measure to quantify network robustness. Once such a measure has been established, we will be able to compare networks, to improve existing networks and to design new networks that are able to continue to perform well when it is subject to failures or attacks. In this paper we survey a large amount of robustness measures on simple, undirected and unweighted graphs, in order to offer a tool for network administrators to evaluate and improve the robustness of their network. The measures discussed in this paper are based on the concepts of connectivity (including reliability polynomials), distance, betweenness and clustering. Some other measures are notions from spectral graph theory, more precisely, they are functions of the Laplacian eigenvalues. In addition to surveying these graph measures, the paper also contains a discussion of their functionality as a measure for topological network robustness.

  7. Photogated humidity-driven motility

    Science.gov (United States)

    Zhang, Lidong; Liang, Haoran; Jacob, Jolly; Naumov, Panče

    2015-06-01

    Hygroinduced motion is a fundamental process of energy conversion that is essential for applications that require contactless actuation in response to the day-night rhythm of atmospheric humidity. Here we demonstrate that mechanical bistability caused by rapid and anisotropic adsorption and desorption of water vapour by a flexible dynamic element that harnesses the chemical potential across very small humidity gradients for perpetual motion can be effectively modulated with light. A mechanically robust material capable of rapid exchange of water with the surroundings is prepared that undergoes swift locomotion in effect to periodic shape reconfiguration with turnover frequency of <150 min-1. The element can lift objects ~85 times heavier and can transport cargos ~20 times heavier than itself. Having an azobenzene-containing conjugate as a photoactive dopant, this entirely humidity-driven self-actuation can be controlled remotely with ultraviolet light, thus setting a platform for next-generation smart biomimetic hybrids.

  8. Robust changes in expression of brain-derived neurotrophic factor (BDNF) mRNA and protein across the brain do not translate to detectable changes in BDNF levels in CSF or plasma.

    Science.gov (United States)

    Lanz, Thomas A; Bove, Susan E; Pilsmaker, Catherine D; Mariga, Abigail; Drummond, Elena M; Cadelina, Gregory W; Adamowicz, Wendy O; Swetter, Brentt J; Carmel, Sharon; Dumin, Jo Ann; Kleiman, Robin J

    2012-09-01

    Adult rats were treated acutely with peripheral kainic acid (KA), and changes in brain-derived neurotrophic factor (BDNF) mRNA and protein were tracked over time across multiple brain regions. Despite robust elevation in both mRNA and protein in multiple brain regions, plasma BDNF was unchanged and cerebrospinal fluid (CSF) BDNF levels remained undetectable. Primary neurons were then treated with KA. BDNF was similarly elevated within neurons, but was undetectable in neuronal media. Thus, while deficits in BDNF signaling have been implicated in a number of diseases, these data suggest that extracellular concentrations of BDNF may not be a facile biomarker for changes in neurons.

  9. Robust expertise effects in right FFA.

    Science.gov (United States)

    McGugin, Rankin Williams; Newton, Allen T; Gore, John C; Gauthier, Isabel

    2014-10-01

    The fusiform face area (FFA) is one of several areas in occipito-temporal cortex whose activity is correlated with perceptual expertise for objects. Here, we investigate the robustness of expertise effects in FFA and other areas to a strong task manipulation that increases both perceptual and attentional demands. With high-resolution fMRI at 7T, we measured responses to images of cars, faces and a category globally visually similar to cars (sofas) in 26 subjects who varied in expertise with cars, in (a) a low load 1-back task with a single object category and (b) a high load task in which objects from two categories were rapidly alternated and attention was required to both categories. The low load condition revealed several areas more active as a function of expertise, including both posterior and anterior portions of FFA bilaterally (FFA1/FFA2, respectively). Under high load, fewer areas were positively correlated with expertise and several areas were even negatively correlated, but the expertise effect in face-selective voxels in the anterior portion of FFA (FFA2) remained robust. Finally, we found that behavioral car expertise also predicted increased responses to sofa images but no behavioral advantages in sofa discrimination, suggesting that global shape similarity to a category of expertise is enough to elicit a response in FFA and other areas sensitive to experience, even when the category itself is not of special interest. The robustness of expertise effects in right FFA2 and the expertise effects driven by visual similarity both argue against attention being the sole determinant of expertise effects in extrastriate areas.

  10. Robust Aircraft Squadron Scheduling in the Face of Absenteeism

    Science.gov (United States)

    2008-03-01

    shows that not much research has been done in this area. Moz and Pato expressed the need for arranging a robust schedule more specifically so that...minimize shift changes with regard to the current one. (Moz& Pato , 2004: 668) While Moz& Pato don’t address robust schedules, the problem they mention...Computers and Operations Research, 32(6), 1451-1476. (2005) (20) Moz, M., & Pato , M. V. “Solving the problem of rerostering nurse schedules with hard

  11. Robust H∞ Control of Hamiltonian System with Uncertainty

    Institute of Scientific and Technical Information of China (English)

    薛安成; 梅生伟; 胡伟; 周原

    2003-01-01

    This paper investigates the robust H∞ problem for a class of generalized forced Hamiltonian systems with uncertainties. The robust L2-gain was proved for the Hamiltonian with a sufficient condition for stable control of multimachine power systems expressed as a matrix algebraic inequality. A similar sufficient condition was then extended to the robust H∞ control of Hamiltonian systems to construct the state feedback H∞ control law. A numerical example is given to verify the validity of the proposed control scheme, which shows the effectiveness and promising application of the method.

  12. Reactive oxygen species and PI3K/Akt signaling play key roles in the induction of Nrf2-driven heme oxygenase-1 expression in sulforaphane-treated human mesothelioma MSTO-211H cells.

    Science.gov (United States)

    Lee, Yoon-Jin; Jeong, Hyang-Yun; Kim, Yong-Bae; Lee, Yong-Jin; Won, Seong Youn; Shim, Jung-Hyun; Cho, Moon-Kyun; Nam, Hae-Seon; Lee, Sang-Han

    2012-02-01

    The nuclear factor erythroid-derived 2 related factor 2 (Nrf2)/heme oxygenase (HO)-1 induction plays cytoprotective roles against oxidative injury, apoptosis, and anticancer therapy; however, little is known about its regulation in human mesothelioma MSTO-211H cells. In this study, we investigated Nrf2/HO-1 induction in response to sulforaphane and determined the signaling pathways involved in this process. Sulforaphane treatment decreased cell viability and triggered a rapid and transient increase in the intracellular ROS levels. Pretreatment with N-acetylcysteine (NAC) prevented sulforaphane-induced cytotoxicity. Erk1/2 was activated within 1h of sulforaphane addition, whereas Akt phosphorylation was suppressed until the first 8h, and was then maintained at an elevated level until 72h, displaying a biphasic regulatory feature. Nrf2 protein levels in both nuclear and whole cell lysates were increased after sulforaphane treatment and were decreased by pretreatment with NAC, actinomycin D and cycloheximide. Activation of the Nrf2/HO-1 system after sulforaphane treatment was suppressed by pretreatment with NAC or Ly294002, a PI3K inhibitor. Knockdown of Nrf2 with siRNA decreased cell viability and attenuated sulforaphane-induced HO-1 up-regulation. Overall, our results indicate that ROS generation and/or activation of PI3K/Akt signaling regulate cell survival and Nrf2-driven HO-1 expression in sulforaphane-treated MSTO-211H cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Theoretical Framework for Robustness Evaluation

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard

    2011-01-01

    This paper presents a theoretical framework for evaluation of robustness of structural systems, incl. bridges and buildings. Typically modern structural design codes require that ‘the consequence of damages to structures should not be disproportional to the causes of the damages’. However, although...... the importance of robustness for structural design is widely recognized the code requirements are not specified in detail, which makes the practical use difficult. This paper describes a theoretical and risk based framework to form the basis for quantification of robustness and for pre-normative guidelines...

  14. Robustness Analysis of Kinetic Structures

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Sørensen, John Dalsgaard

    2009-01-01

    The present paper considers robustness of kinetic structures. Robustness of structures has obtained a renewed interest due to a much more frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure. Especially for these types of structural syst...... systems, it is of interest to investigate how robust the structures are, or what happens if a structural element is added to or removed from the original structure. The present paper discusses this issue for kinetic structures in architecture....

  15. Robustness of airline route networks

    Science.gov (United States)

    Lordan, Oriol; Sallan, Jose M.; Escorihuela, Nuria; Gonzalez-Prieto, David

    2016-03-01

    Airlines shape their route network by defining their routes through supply and demand considerations, paying little attention to network performance indicators, such as network robustness. However, the collapse of an airline network can produce high financial costs for the airline and all its geographical area of influence. The aim of this study is to analyze the topology and robustness of the network route of airlines following Low Cost Carriers (LCCs) and Full Service Carriers (FSCs) business models. Results show that FSC hubs are more central than LCC bases in their route network. As a result, LCC route networks are more robust than FSC networks.

  16. Robust mechanisms of ventral furrow invagination require the combination of cellular shape changes

    Science.gov (United States)

    Conte, Vito; Muñoz, José J.; Baum, Buzz; Miodownik, Mark

    2009-03-01

    Ventral furrow formation in Drosophila is the first large-scale morphogenetic movement during the life of the embryo, and is driven by co-ordinated changes in the shape of individual epithelial cells within the cellular blastoderm. Although many of the genes involved have been identified, the details of the mechanical processes that convert local changes in gene expression into whole-scale changes in embryonic form remain to be fully understood. Biologists have identified two main cell deformation modes responsible for ventral furrow invagination: constriction of the apical ends of the cells (apical wedging) and deformation along their apical-basal axes (radial lengthening/shortening). In this work, we used a computer 2D finite element model of ventral furrow formation to investigate the ability of different combinations of three plausible elementary active cell shape changes to bring about epithelial invagination: ectodermal apical-basal shortening, mesodermal apical-basal lengthening/shortening and mesodermal apical constriction. We undertook a systems analysis of the biomechanical system, which revealed many different combinations of active forces (invagination mechanisms) were able to generate a ventral furrow. Two important general features were revealed. First that combinations of shape changes are the most robust to environmental and mutational perturbation, in particular those combining ectodermal pushing and mesodermal wedging. Second, that ectodermal pushing plays a big part in all of the robust mechanisms (mesodermal forces alone do not close the furrow), and this provides evidence that it may be an important element in the mechanics of invagination in Drosophila.

  17. Robustness with respect to disturbance model uncertainty: Theory and application to autopilot performance analysis

    Directory of Open Access Journals (Sweden)

    Davison Daniel E.

    2000-01-01

    Full Text Available This paper deals with the notion of disturbance model uncertainty. The disturbance is modeled as the output of a first-order filter which is driven by white noise and whose bandwidth and gain are uncertain. An analytical expression for the steady-state output variance as a function of the uncertain bandwidth and gain is derived, and several properties of this variance function are analyzed. Two notions, those of disturbance bandwidth margin and disturbance gain margin are also introduced. These tools are then applied to the analysis of a simple altitude-hold autopilot system in the presence of turbulence where the turbulence scale is treated as an uncertain parameter. It is shown that the autopilot, which is satisfactory for nominal turbulence scale, may be inadequate when the uncertainty is taken into account. Moreover, it is proven that, in order to obtain a design that provides robust performance in the face of turbulence scale uncertainty, it is necessary to substantially increase the controller bandwidth, even if one is willing to sacrifice the autopilot's holding ability and stability robustness.

  18. An integer optimization algorithm for robust identification of non-linear gene regulatory networks

    Directory of Open Access Journals (Sweden)

    Chemmangattuvalappil Nishanth

    2012-09-01

    Full Text Available Abstract Background Reverse engineering gene networks and identifying regulatory interactions are integral to understanding cellular decision making processes. Advancement in high throughput experimental techniques has initiated innovative data driven analysis of gene regulatory networks. However, inherent noise associated with biological systems requires numerous experimental replicates for reliable conclusions. Furthermore, evidence of robust algorithms directly exploiting basic biological traits are few. Such algorithms are expected to be efficient in their performance and robust in their prediction. Results We have developed a network identification algorithm to accurately infer both the topology and strength of regulatory interactions from time series gene expression data in the presence of significant experimental noise and non-linear behavior. In this novel formulism, we have addressed data variability in biological systems by integrating network identification with the bootstrap resampling technique, hence predicting robust interactions from limited experimental replicates subjected to noise. Furthermore, we have incorporated non-linearity in gene dynamics using the S-system formulation. The basic network identification formulation exploits the trait of sparsity of biological interactions. Towards that, the identification algorithm is formulated as an integer-programming problem by introducing binary variables for each network component. The objective function is targeted to minimize the network connections subjected to the constraint of maximal agreement between the experimental and predicted gene dynamics. The developed algorithm is validated using both in silico and experimental data-sets. These studies show that the algorithm can accurately predict the topology and connection strength of the in silico networks, as quantified by high precision and recall, and small discrepancy between the actual and predicted kinetic parameters

  19. Data-driven normalization strategies for high-throughput quantitative RT-PCR

    Directory of Open Access Journals (Sweden)

    Suzuki Harukazu

    2009-04-01

    Full Text Available Abstract Background High-throughput real-time quantitative reverse transcriptase polymerase chain reaction (qPCR is a widely used technique in experiments where expression patterns of genes are to be profiled. Current stage technology allows the acquisition of profiles for a moderate number of genes (50 to a few thousand, and this number continues to grow. The use of appropriate normalization algorithms for qPCR-based data is therefore a highly important aspect of the data preprocessing pipeline. Results We present and evaluate two data-driven normalization methods that directly correct for technical variation and represent robust alternatives to standard housekeeping gene-based approaches. We evaluated the performance of these methods against a single gene housekeeping gene method and our results suggest that quantile normalization performs best. These methods are implemented in freely-available software as an R package qpcrNorm distributed through the Bioconductor project. Conclusion The utility of the approaches that we describe can be demonstrated most clearly in situations where standard housekeeping genes are regulated by some experimental condition. For large qPCR-based data sets, our approaches represent robust, data-driven strategies for normalization.

  20. Robust and resistant 2D shape alignment

    DEFF Research Database (Denmark)

    Larsen, Rasmus; Eiriksson, Hrafnkell

    2001-01-01

    \\_\\$\\backslash\\$infty\\$ norm alignments are formulated as linear programming problems. The linear vector function formulation along with the different norms results in alignment methods that are both resistant from influence from outliers, robust wrt. errors in the annotation and capable of handling missing datapoints......We express the alignment of 2D shapes as the minimization of the norm of a linear vector function. The minimization is done in the \\$l\\_1\\$, \\$l\\_2\\$ and the \\$l\\_\\$\\backslash\\$infty\\$ norms using well known standard numerical methods. In particular, the \\$l\\_1\\$ and the \\$l...

  1. Multifidelity Robust Aeroelastic Design Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Nielsen Engineering & Research (NEAR) proposes a new method to generate mathematical models of wind-tunnel models and flight vehicles for robust aeroelastic...

  2. Robust Portfolio Optimization Using Pseudodistances.

    Science.gov (United States)

    Toma, Aida; Leoni-Aubin, Samuela

    2015-01-01

    The presence of outliers in financial asset returns is a frequently occurring phenomenon which may lead to unreliable mean-variance optimized portfolios. This fact is due to the unbounded influence that outliers can have on the mean returns and covariance estimators that are inputs in the optimization procedure. In this paper we present robust estimators of mean and covariance matrix obtained by minimizing an empirical version of a pseudodistance between the assumed model and the true model underlying the data. We prove and discuss theoretical properties of these estimators, such as affine equivariance, B-robustness, asymptotic normality and asymptotic relative efficiency. These estimators can be easily used in place of the classical estimators, thereby providing robust optimized portfolios. A Monte Carlo simulation study and applications to real data show the advantages of the proposed approach. We study both in-sample and out-of-sample performance of the proposed robust portfolios comparing them with some other portfolios known in literature.

  3. Robust inspection and interpretation techniques

    Energy Technology Data Exchange (ETDEWEB)

    Marriott, D.L. (Stress Engineering Services, Cincinnati, OH (United States))

    1993-05-01

    This paper explores the value of approximate methods of a specific type, as an efficient aid to performing residual life assessments, particularly when input data are incomplete. These methods, referred to as [open quotes]robust[close quotes] have the desirable attributes of providing satisfactory answers using less-than-perfect input, and being very economical in time of execution. Some examples of robust methods, which have been used successfully in high temperature design and fracture evaluations, are presented. 17 refs., 12 figs.

  4. Robust methods for data reduction

    CERN Document Server

    Farcomeni, Alessio

    2015-01-01

    Robust Methods for Data Reduction gives a non-technical overview of robust data reduction techniques, encouraging the use of these important and useful methods in practical applications. The main areas covered include principal components analysis, sparse principal component analysis, canonical correlation analysis, factor analysis, clustering, double clustering, and discriminant analysis.The first part of the book illustrates how dimension reduction techniques synthesize available information by reducing the dimensionality of the data. The second part focuses on cluster and discriminant analy

  5. Real Time & Power Efficient Adaptive - Robust Control

    Science.gov (United States)

    Ioan Gliga, Lavinius; Constantin Mihai, Cosmin; Lupu, Ciprian; Popescu, Dumitru

    2017-01-01

    A design procedure for a control system suited for dynamic variable processes is presented in this paper. The proposed adaptive - robust control strategy considers both adaptive control advantages and robust control benefits. It estimates the degradation of the system’s performances due to the dynamic variation in the process and it then utilizes it to determine when the system must be adapted with a redesign of the robust controller. A single integral criterion is used for the identification of the process, and for the design of the control algorithm, which is expressed in direct form, through a cost function defined in the space of the parameters of both the process and the controller. For the minimization of this nonlinear function, an adequate mathematical programming minimization method is used. The theoretical approach presented in this paper was validated for a closed loop control system, simulated in an application developed in C. Because of the reduced number of operations, this method is suitable for implementation on fast processes. Due to its effectiveness, it increases the idle time of the CPU, thereby saving electrical energy.

  6. How robust is a robust policy? A comparative analysis of alternative robustness metrics for supporting robust decision analysis.

    Science.gov (United States)

    Kwakkel, Jan; Haasnoot, Marjolijn

    2015-04-01

    In response to climate and socio-economic change, in various policy domains there is increasingly a call for robust plans or policies. That is, plans or policies that performs well in a very large range of plausible futures. In the literature, a wide range of alternative robustness metrics can be found. The relative merit of these alternative conceptualizations of robustness has, however, received less attention. Evidently, different robustness metrics can result in different plans or policies being adopted. This paper investigates the consequences of several robustness metrics on decision making, illustrated here by the design of a flood risk management plan. A fictitious case, inspired by a river reach in the Netherlands is used. The performance of this system in terms of casualties, damages, and costs for flood and damage mitigation actions is explored using a time horizon of 100 years, and accounting for uncertainties pertaining to climate change and land use change. A set of candidate policy options is specified up front. This set of options includes dike raising, dike strengthening, creating more space for the river, and flood proof building and evacuation options. The overarching aim is to design an effective flood risk mitigation strategy that is designed from the outset to be adapted over time in response to how the future actually unfolds. To this end, the plan will be based on the dynamic adaptive policy pathway approach (Haasnoot, Kwakkel et al. 2013) being used in the Dutch Delta Program. The policy problem is formulated as a multi-objective robust optimization problem (Kwakkel, Haasnoot et al. 2014). We solve the multi-objective robust optimization problem using several alternative robustness metrics, including both satisficing robustness metrics and regret based robustness metrics. Satisficing robustness metrics focus on the performance of candidate plans across a large ensemble of plausible futures. Regret based robustness metrics compare the

  7. The 'Robust' roster: exploring the nurse rostering process.

    Science.gov (United States)

    Drake, Robert G

    2014-09-01

    To identify and explore the relationships between stages of the rostering process and the robustness of the worked roster. Once published, a nurse roster is often subject to many changes. However, post-approval changes and their implications are rarely examined. Consequently, there is little evidence to determine whether a 'worked' roster was safe, efficient or fair. Electronic rostering systems provide greater transparency of the rostering process allowing postapproval changes to be examined more thoroughly. Using quantitative data, this study compares the outcomes from different stages of the roster process with the shifts breaking roster rules. This study covered the period November 2009-January 2013 and included forty-two roster periods from fifteen wards. For each of the rosters, data specifying the type of shift assignment (request, manual and automatic) and number of shifts changed after approval (response variables) were captured. Linear regression analysis was then used to identify and explore the relationships between these response variables and the number of shifts breaking rules. Roster robustness is unaffected by the number of staff requests, Yet, how shifts are assigned before approval and the number of changes postapproval have a marked effect on the robustness of the roster. Roster 'robustness' is determined by the quality of the approved roster and subsequent postapproval demand- and supply-driven changes. Despite evidence that e-rostering can improve roster robustness, many Ward Managers prefer to roster manually. On some wards, rosters are approved, regardless of the number of rule breakages occurring. © 2014 John Wiley & Sons Ltd.

  8. Query Driven Visualization

    CERN Document Server

    Buddelmeijer, Hugo

    2011-01-01

    The request driven way of deriving data in Astro-WISE is extended to a query driven way of visualization. This allows scientists to focus on the science they want to perform, because all administration of their data is automated. This can be done over an abstraction layer that enhances control and flexibility for the scientist.

  9. Reactivity Monitoring of Accelerator-Driven Nuclear Reactor Systems

    NARCIS (Netherlands)

    Uyttenhove, W.

    2016-01-01

    This thesis provides a methodology and set-up of a reactivity monitoring tool for Accelerator-Driven Systems (ADS). The reactivity monitoring tool should guarantee the operation of an ADS at a safe margin from criticality. Robustness is assured in different aspects of the monitoring tool: the choice

  10. Reactivity Monitoring of Accelerator-Driven Nuclear Reactor Systems

    NARCIS (Netherlands)

    Uyttenhove, W.

    2016-01-01

    This thesis provides a methodology and set-up of a reactivity monitoring tool for Accelerator-Driven Systems (ADS). The reactivity monitoring tool should guarantee the operation of an ADS at a safe margin from criticality. Robustness is assured in different aspects of the monitoring tool: the choice

  11. Optimizing the robustness of electrical power systems against cascading failures

    CERN Document Server

    Zhang, Yingrui

    2016-01-01

    Electrical power systems are one of the most important infrastructures that support our society. However, their vulnerabilities have raised great concern recently due to several large-scale blackouts around the world. In this paper, we investigate the robustness of power systems against cascading failures initiated by a random attack. This is done under a simple yet useful model based on global and equal redistribution of load upon failures. We provide a complete understanding of system robustness by i) deriving an expression for the final system size as a function of the size of initial attacks; ii) deriving the critical attack size after which system breaks down completely; iii) showing that complete system breakdown takes place through a first-order (i.e., discontinuous) transition in terms of the attack size; and iv) establishing the optimal load-capacity distribution that maximizes robustness. In particular, we show that robustness is maximized when the difference between the capacity and initial load is...

  12. Attractive ellipsoids in robust control

    CERN Document Server

    Poznyak, Alexander; Azhmyakov, Vadim

    2014-01-01

    This monograph introduces a newly developed robust-control design technique for a wide class of continuous-time dynamical systems called the “attractive ellipsoid method.” Along with a coherent introduction to the proposed control design and related topics, the monograph studies nonlinear affine control systems in the presence of uncertainty and presents a constructive and easily implementable control strategy that guarantees certain stability properties. The authors discuss linear-style feedback control synthesis in the context of the above-mentioned systems. The development and physical implementation of high-performance robust-feedback controllers that work in the absence of complete information is addressed, with numerous examples to illustrate how to apply the attractive ellipsoid method to mechanical and electromechanical systems. While theorems are proved systematically, the emphasis is on understanding and applying the theory to real-world situations. Attractive Ellipsoids in Robust Control will a...

  13. A Robust Enough Virtue Epistemology

    DEFF Research Database (Denmark)

    Broncano-Berrocal, Fernando

    2016-01-01

    What is the nature of knowledge? A popular answer to that long-standing question comes from robust virtue epistemology, whose key idea is that knowing is just a matter of succeeding cognitively—i.e., coming to believe a proposition truly—due to an exercise of cognitive ability. Versions of robust...... virtue epistemology further developing and systematizing this idea offer different accounts of the relation that must hold between an agent’s cognitive success and the exercise of her cognitive abilities as well as of the very nature of those abilities. This paper aims to give a new robust virtue...... epistemological account of knowledge based on a different understanding of the nature and structure of the kind of abilities that give rise to knowledge....

  14. Advances in robust fractional control

    CERN Document Server

    Padula, Fabrizio

    2015-01-01

    This monograph presents design methodologies for (robust) fractional control systems. It shows the reader how to take advantage of the superior flexibility of fractional control systems compared with integer-order systems in achieving more challenging control requirements. There is a high degree of current interest in fractional systems and fractional control arising from both academia and industry and readers from both milieux are catered to in the text. Different design approaches having in common a trade-off between robustness and performance of the control system are considered explicitly. The text generalizes methodologies, techniques and theoretical results that have been successfully applied in classical (integer) control to the fractional case. The first part of Advances in Robust Fractional Control is the more industrially-oriented. It focuses on the design of fractional controllers for integer processes. In particular, it considers fractional-order proportional-integral-derivative controllers, becau...

  15. Robust estimation and hypothesis testing

    CERN Document Server

    Tiku, Moti L

    2004-01-01

    In statistical theory and practice, a certain distribution is usually assumed and then optimal solutions sought. Since deviations from an assumed distribution are very common, one cannot feel comfortable with assuming a particular distribution and believing it to be exactly correct. That brings the robustness issue in focus. In this book, we have given statistical procedures which are robust to plausible deviations from an assumed mode. The method of modified maximum likelihood estimation is used in formulating these procedures. The modified maximum likelihood estimators are explicit functions of sample observations and are easy to compute. They are asymptotically fully efficient and are as efficient as the maximum likelihood estimators for small sample sizes. The maximum likelihood estimators have computational problems and are, therefore, elusive. A broad range of topics are covered in this book. Solutions are given which are easy to implement and are efficient. The solutions are also robust to data anomali...

  16. Onion structure and network robustness

    CERN Document Server

    Wu, Zhi-Xi; 10.1103/PhysRevE.84.026106

    2011-01-01

    In a recent work [Proc. Natl. Acad. Sci. USA 108, 3838 (2011)], Schneider et al. proposed a new measure for network robustness and investigated optimal networks with respect to this quantity. For networks with a power-law degree distribution, the optimized networks have an onion structure-high-degree vertices forming a core with radially decreasing degrees and an over-representation of edges within the same radial layer. In this paper we relate the onion structure to graphs with good expander properties (another characterization of robust network) and argue that networks of skewed degree distributions with large spectral gaps (and thus good expander properties) are typically onion structured. Furthermore, we propose a generative algorithm producing synthetic scale-free networks with onion structure, circumventing the optimization procedure of Schneider et al. We validate the robustness of our generated networks against malicious attacks and random removals.

  17. Robust Disaster Recovery System Model

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Highly security-critical system should possess features of continuous service. We present a new Robust Disaster Recovery System Model (RDRSM). Through strengthening the ability of safe communications, RDRSM guarantees the secure and reliable command on disaster recovery. Its self-supervision capability can monitor the integrality and security of disaster recovery system itself. By 2D and 3D real-time visible platform provided by GIS, GPS and RS, the model makes the using, management and maintenance of disaster recovery system easier. RDRSM possesses predominant features of security, robustness and controllability. And it can be applied to highly security-critical environments such as E-government and bank. Conducted by RDRSM, an important E-government disaster recovery system has been constructed successfully. The feasibility of this model is verified by practice. We especially emphasize the significance of some components of the model, such as risk assessment, disaster recovery planning, system supervision and robust communication support.

  18. Robustness of digital artist authentication

    DEFF Research Database (Denmark)

    Jacobsen, Robert; Nielsen, Morten

    In many cases it is possible to determine the authenticity of a painting from digital reproductions of the paintings; this has been demonstrated for a variety of artists and with different approaches. Common to all these methods in digital artist authentication is that the potential of the method...... is in focus, while the robustness has not been considered, i.e. the degree to which the data collection process influences the decision of the method. However, in order for an authentication method to be successful in practice, it needs to be robust to plausible error sources from the data collection....... In this paper we investigate the robustness of the newly proposed authenticity method introduced by the authors based on second generation multiresolution analysis. This is done by modelling a number of realistic factors that can occur in the data collection....

  19. Robust Hitting with Dynamics Shaping

    Science.gov (United States)

    Yashima, Masahito; Yamawaki, Tasuku

    The present paper proposes the trajectory planning based on “the dynamics shaping” for a redundant robotic arm to hit a target robustly toward the desired direction, of which the concept is to shape the robot dynamics appropriately by changing its posture in order to achieve the robust motion. The positional error of the end-effector caused by unknown disturbances converges onto near the singular vector corresponding to its maximum singular value of the output controllability matrix of the robotic arm. Therefore, if we can control the direction of the singular vector by applying the dynamics shaping, we will be able to control the direction of the positional error of the end-effector caused by unknown disturbances. We propose a novel trajectory planning based on the dynamics shaping and verify numerically and experimentally that the robotic arm can robustly hit the target toward the desired direction with a simple open-loop control system even though the disturbance is applied.

  20. Robust Watermarking of Cartographic Images

    Directory of Open Access Journals (Sweden)

    Mauro Barni

    2002-02-01

    Full Text Available We present a method (Text-Based Geometric Normalization—TBGN which, by exploiting the particular content of cartographic images, namely text content, permits to cope with global geometric transformations. First, text is extracted from the to-be-marked map, then text orientation and size are exploited to normalize the image geometry prior to watermark insertion. Watermarking is performed by means of any of the existing algorithms ensuring good robustness against image processing tools. At the decoder side, text is extracted again from the map and used to normalize image geometry. Owing to the robustness of text features with respect to common image manipulations, and to the likely spreading of text all across the digital map, the proposed system exhibits an excellent robustness.

  1. Robust Schur Stability and Robust H^2 Performance

    DEFF Research Database (Denmark)

    Stoustrup, Jakob; Zhao, K.-Y.

    1996-01-01

    In this paper we address the problems of robust stability androbust QTR H^2 performance for uncertain discrete time systemswith nonlinear parametric uncertainties. We consider two families ofsystems with parametric uncertainties described by state space modelswhich offer a fairly general represen...

  2. Asymptotics of robust utility maximization

    CERN Document Server

    Knispel, Thomas

    2012-01-01

    For a stochastic factor model we maximize the long-term growth rate of robust expected power utility with parameter $\\lambda\\in(0,1)$. Using duality methods the problem is reformulated as an infinite time horizon, risk-sensitive control problem. Our results characterize the optimal growth rate, an optimal long-term trading strategy and an asymptotic worst-case model in terms of an ergodic Bellman equation. With these results we propose a duality approach to a "robust large deviations" criterion for optimal long-term investment.

  3. Data-Driven Control of Refrigeration System

    DEFF Research Database (Denmark)

    Vinther, Kasper

    facilities without using a pressure sensor. A single-sensor solution is thus provided, which either reduces the variable costs or increases the robustness of the system by not relying on pressure measurements. MSS is an example of data-driven control and can be applied to a broad class of nonlinear control......Refrigeration is used in a wide range of applications, e.g., for storage of food at low temperatures to prolong shelf life and in air conditioning for occupancy comfort. The main focus of this thesis is control of supermarket refrigeration systems. This market is very competitive...... and it is important to keep the variable costs at a minimum and, if possible, offer products which have higher robustness, performance, and functionality than similar products from competitors. However, the multitude of different system configurations, system complexity, component wear, and changing operating...

  4. Data Driven Constraints for the SVM

    DEFF Research Database (Denmark)

    Darkner, Sune; Clemmensen, Line Katrine Harder

    2012-01-01

    We propose a generalized data driven constraint for support vector machines exemplified by classification of paired observations in general and specifically on the human ear canal. This is particularly interesting in dynamic cases such as tissue movement or pathologies developing over time....... Assuming that two observations of the same subject in different states span a vector, we hypothesise that such structure of the data contains implicit information which can aid the classification, thus the name data driven constraints. We derive a constraint based on the data which allow for the use...... of the ℓ1-norm on the constraint while still allowing for the application of kernels. We specialize the proposed constraint to orthogonality of the vectors between paired observations and the estimated hyperplane. We show that imposing the constraint of orthogonality on the paired data yields a more robust...

  5. Simulations of driven overdamped frictionless hard spheres

    Science.gov (United States)

    Lerner, Edan; Düring, Gustavo; Wyart, Matthieu

    2013-03-01

    We introduce an event-driven simulation scheme for overdamped dynamics of frictionless hard spheres subjected to external forces, neglecting hydrodynamic interactions. Our event-driven approach is based on an exact equation of motion which relates the driving force to the resulting velocities through the geometric information characterizing the underlying network of contacts between the hard spheres. Our method allows for a robust extraction of the instantaneous coordination of the particles as well as contact force statistics and dynamics, under any chosen driving force, in addition to shear flow and compression. It can also be used for generating high-precision jammed packings under shear, compression, or both. We present a number of additional applications of our method.

  6. Image Filtering Driven by Level Curves

    Science.gov (United States)

    Rajwade, Ajit; Banerjee, Arunava; Rangarajan, Anand

    This paper presents an approach to image filtering that is driven by the properties of the iso-valued level curves of the image and their relationship with one another. We explore the relationship of our algorithm to existing probabilistically driven filtering methods such as those based on kernel density estimation, local-mode finding and mean-shift. Extensive experimental results on filtering gray-scale images, color images, gray-scale video and chromaticity fields are presented. In contrast to existing probabilistic methods, in our approach, the selection of the parameter that prevents diffusion across the edge is robustly decoupled from the smoothing of the density itself. Furthermore, our method is observed to produce better filtering results for the same settings of parameters for the filter window size and the edge definition.

  7. Noise-driven phenomena in hysteretic systems

    CERN Document Server

    Dimian, Mihai

    2014-01-01

    Noise-Driven Phenomena in Hysteretic Systems provides a general approach to nonlinear systems with hysteresis driven by noisy inputs, which leads to a unitary framework for the analysis of various stochastic aspects of hysteresis. This book includes integral, differential and algebraic models that are used to describe scalar and vector hysteretic nonlinearities originating from various areas of science and engineering. The universality of the authors approach is also reflected by the diversity of the models used to portray the input noise, from the classical Gaussian white noise to its impulsive forms, often encountered in economics and biological systems, and pink noise, ubiquitous in multi-stable electronic systems. The book is accompanied by HysterSoft© - a robust simulation environment designed to perform complex hysteresis modeling – that can be used by the reader to reproduce many of the results presented in the book as well as to research both disruptive and constructive effects of noise in hysteret...

  8. Robust dual-response optimization

    NARCIS (Netherlands)

    Yanikoglu, Ihsan; den Hertog, Dick; Kleijnen, J.P.C.

    2016-01-01

    This article presents a robust optimization reformulation of the dual-response problem developed in response surface methodology. The dual-response approach fits separate models for the mean and the variance and analyzes these two models in a mathematical optimization setting. We use metamodels esti

  9. Theoretical Framework for Robustness Evaluation

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard

    2011-01-01

    This paper presents a theoretical framework for evaluation of robustness of structural systems, incl. bridges and buildings. Typically modern structural design codes require that ‘the consequence of damages to structures should not be disproportional to the causes of the damages’. However, althou...

  10. Robust control design with MATLAB

    CERN Document Server

    Gu, Da-Wei; Konstantinov, Mihail M

    2013-01-01

    Robust Control Design with MATLAB® (second edition) helps the student to learn how to use well-developed advanced robust control design methods in practical cases. To this end, several realistic control design examples from teaching-laboratory experiments, such as a two-wheeled, self-balancing robot, to complex systems like a flexible-link manipulator are given detailed presentation. All of these exercises are conducted using MATLAB® Robust Control Toolbox 3, Control System Toolbox and Simulink®. By sharing their experiences in industrial cases with minimum recourse to complicated theories and formulae, the authors convey essential ideas and useful insights into robust industrial control systems design using major H-infinity optimization and related methods allowing readers quickly to move on with their own challenges. The hands-on tutorial style of this text rests on an abundance of examples and features for the second edition: ·        rewritten and simplified presentation of theoretical and meth...

  11. Robust Portfolio Optimization Using Pseudodistances

    Science.gov (United States)

    2015-01-01

    The presence of outliers in financial asset returns is a frequently occurring phenomenon which may lead to unreliable mean-variance optimized portfolios. This fact is due to the unbounded influence that outliers can have on the mean returns and covariance estimators that are inputs in the optimization procedure. In this paper we present robust estimators of mean and covariance matrix obtained by minimizing an empirical version of a pseudodistance between the assumed model and the true model underlying the data. We prove and discuss theoretical properties of these estimators, such as affine equivariance, B-robustness, asymptotic normality and asymptotic relative efficiency. These estimators can be easily used in place of the classical estimators, thereby providing robust optimized portfolios. A Monte Carlo simulation study and applications to real data show the advantages of the proposed approach. We study both in-sample and out-of-sample performance of the proposed robust portfolios comparing them with some other portfolios known in literature. PMID:26468948

  12. Robust power system frequency control

    CERN Document Server

    Bevrani, Hassan

    2008-01-01

    Emphasizes the physical and engineering aspects of the power system frequency control design problem while providing a conceptual understanding of frequency regulation and application of robust control techniques. This book summarizes the author's research outcomes, contributions and experiences with power system frequency regulation.

  13. Mental Models: A Robust Definition

    Science.gov (United States)

    Rook, Laura

    2013-01-01

    Purpose: The concept of a mental model has been described by theorists from diverse disciplines. The purpose of this paper is to offer a robust definition of an individual mental model for use in organisational management. Design/methodology/approach: The approach adopted involves an interdisciplinary literature review of disciplines, including…

  14. Hints for practical robust optimization

    NARCIS (Netherlands)

    Gorissen, B.L.; Yanikoglu, I.; den Hertog, D.

    2013-01-01

    Robust optimization (RO) is a young and active research field that has been mainly developed in the last 15 years. RO techniques are very useful for practice and not difficult to understand for practitioners. It is therefore remarkable that real-life applications of RO are still lagging behind; ther

  15. Mental Models: A Robust Definition

    Science.gov (United States)

    Rook, Laura

    2013-01-01

    Purpose: The concept of a mental model has been described by theorists from diverse disciplines. The purpose of this paper is to offer a robust definition of an individual mental model for use in organisational management. Design/methodology/approach: The approach adopted involves an interdisciplinary literature review of disciplines, including…

  16. Robust Simulations and Significant Separations

    CERN Document Server

    Fortnow, Lance

    2010-01-01

    We define and study a new notion of "robust simulations" between complexity classes which is intermediate between the traditional notions of infinitely-often and almost-everywhere, as well as a corresponding notion of "significant separations". A language L has a robust simulation in a complexity class C if there is a language in C which agrees with L on arbitrarily large polynomial stretches of input lengths. There is a significant separation of L from C if there is no robust simulation of L in C. The new notion of simulation is a cleaner and more natural notion of simulation than the infinitely-often notion. We show that various implications in complexity theory such as the collapse of PH if NP = P and the Karp-Lipton theorem have analogues for robust simulations. We then use these results to prove that most known separations in complexity theory, such as hierarchy theorems, fixed polynomial circuit lower bounds, time-space tradeoffs, and the theorems of Allender and Williams, can be strengthened to signifi...

  17. A robust adaptive robot controller

    NARCIS (Netherlands)

    Berghuis, Harry; Ortega, Romeo; Nijmeijer, Henk

    1993-01-01

    A globally convergent adaptive control scheme for robot motion control with the following features is proposed. First, the adaptation law possesses enhanced robustness with respect to noisy velocity measurements. Second, the controller does not require the inclusion of high gain loops that may excit

  18. On Robustness of Power Grids

    NARCIS (Netherlands)

    Koç, Y.

    2015-01-01

    Current and future trends in environmental, economical, and human-caused factors (such as power demand growth, over-ageing of assets in power grids, and extreme weather conditions) challenge power grid robustness in the near future, necessitating research to better analyse and understand the notion

  19. Neutrino Physics with Accelerator Driven Subcritical Reactors

    CERN Document Server

    Ciuffoli, Emilio; Zhao, Fengyi

    2015-01-01

    Accelerator driven system (ADS) subcritical nuclear reactors are under development around the world. They will be intense sources of free, 30-50 MeV antimuon decay at rest antimuon neutrinos. These ADS reactor neutrinos can provide a robust test of the LSND anomaly and a precise measurement of the leptonic CP-violating phase delta, including sign(cos(delta)). The first phase of many ADS programs includes the construction of a low energy, high intensity proton or deuteron accelerator, which can yield competitive bounds on sterile neutrinos.

  20. Laser-Driven Fusion.

    Science.gov (United States)

    Gibson, A. F.

    1980-01-01

    Discusses the present status and future prospects of laser-driven fusion. Current research (which is classified under three main headings: laser-matter interaction processes, compression, and laser development) is also presented. (HM)

  1. Maximizing hysteretic losses in magnetic ferrite nanoparticles via model-driven synthesis and materials optimization.

    Science.gov (United States)

    Chen, Ritchie; Christiansen, Michael G; Anikeeva, Polina

    2013-10-22

    This article develops a set of design guidelines for maximizing heat dissipation characteristics of magnetic ferrite MFe2O4 (M = Mn, Fe, Co) nanoparticles in alternating magnetic fields. Using magnetic and structural nanoparticle characterization, we identify key synthetic parameters in the thermal decomposition of organometallic precursors that yield optimized magnetic nanoparticles over a wide range of sizes and compositions. The developed synthetic procedures allow for gram-scale production of magnetic nanoparticles stable in physiological buffer for several months. Our magnetic nanoparticles display some of the highest heat dissipation rates, which are in qualitative agreement with the trends predicted by a dynamic hysteresis model of coherent magnetization reversal in single domain magnetic particles. By combining physical simulations with robust scalable synthesis and materials characterization techniques, this work provides a pathway to a model-driven design of magnetic nanoparticles tailored to a variety of biomedical applications ranging from cancer hyperthermia to remote control of gene expression.

  2. Discovery Driven Growth

    DEFF Research Database (Denmark)

    Bukh, Per Nikolaj

    2009-01-01

    Anmeldelse af Discovery Driven Growh : A breakthrough process to reduce risk and seize opportunity, af Rita G. McGrath & Ian C. MacMillan, Boston: Harvard Business Press. Udgivelsesdato: 14 august......Anmeldelse af Discovery Driven Growh : A breakthrough process to reduce risk and seize opportunity, af Rita G. McGrath & Ian C. MacMillan, Boston: Harvard Business Press. Udgivelsesdato: 14 august...

  3. Robust regularized singular value decomposition with application to mortality data

    KAUST Repository

    Zhang, Lingsong

    2013-09-01

    We develop a robust regularized singular value decomposition (RobRSVD) method for analyzing two-way functional data. The research is motivated by the application of modeling human mortality as a smooth two-way function of age group and year. The RobRSVD is formulated as a penalized loss minimization problem where a robust loss function is used to measure the reconstruction error of a low-rank matrix approximation of the data, and an appropriately defined two-way roughness penalty function is used to ensure smoothness along each of the two functional domains. By viewing the minimization problem as two conditional regularized robust regressions, we develop a fast iterative reweighted least squares algorithm to implement the method. Our implementation naturally incorporates missing values. Furthermore, our formulation allows rigorous derivation of leaveone- row/column-out cross-validation and generalized cross-validation criteria, which enable computationally efficient data-driven penalty parameter selection. The advantages of the new robust method over nonrobust ones are shown via extensive simulation studies and the mortality rate application. © Institute of Mathematical Statistics, 2013.

  4. Engineering robust and tunable spatial structures with synthetic gene circuits.

    Science.gov (United States)

    Kong, Wentao; Blanchard, Andrew E; Liao, Chen; Lu, Ting

    2017-01-25

    Controllable spatial patterning is a major goal for the engineering of biological systems. Recently, synthetic gene circuits have become promising tools to achieve the goal; however, they need to possess both functional robustness and tunability in order to facilitate future applications. Here we show that, by harnessing the dual signaling and antibiotic features of nisin, simple synthetic circuits can direct Lactococcus lactis populations to form programmed spatial band-pass structures that do not require fine-tuning and are robust against environmental and cellular context perturbations. Although robust, the patterns are highly tunable, with their band widths specified by the external nisin gradient and cellular nisin immunity. Additionally, the circuits can direct cells to consistently generate designed patterns, even when the gradient is driven by structured nisin-producing bacteria and the patterning cells are composed of multiple species. A mathematical model successfully reproduces all of the observed patterns. Furthermore, the circuits allow us to establish predictable structures of synthetic communities and controllable arrays of cellular stripes and spots in space. This study offers new synthetic biology tools to program spatial structures. It also demonstrates that a deep mining of natural functionalities of living systems is a valuable route to build circuit robustness and tunability.

  5. Robust Reliability or reliable robustness? - Integrated consideration of robustness and reliability aspects

    DEFF Research Database (Denmark)

    Kemmler, S.; Eifler, Tobias; Bertsche, B.

    2015-01-01

    products are and vice versa. For a comprehensive understanding and to use existing synergies between both domains, this paper discusses the basic principles of Reliability- and Robust Design theory. The development of a comprehensive model will enable an integrated consideration of both domains...

  6. Robust eigenstructure clustering by non-smooth optimisation

    Science.gov (United States)

    Dao, Minh Ngoc; Noll, Dominikus; Apkarian, Pierre

    2015-08-01

    We extend classical eigenstructure assignment to more realistic problems, where additional performance and robustness specifications arise. Our aim is to combine time-domain constraints, as reflected by pole location and eigenvector structure, with frequency-domain objectives such as the H2, H∞ or Hankel norms. Using pole clustering, we allow poles to move in polydisks of prescribed size around their nominal values, driven by optimisation. Eigenelements, that is poles and eigenvectors, are allowed to move simultaneously and serve as decision variables in a specialised non-smooth optimisation technique. Two aerospace applications illustrate the power of the new method.

  7. Cooperativity of Negative Autoregulation Confers Increased Mutational Robustness

    Science.gov (United States)

    Marciano, David C.; Lua, Rhonald C.; Herman, Christophe; Lichtarge, Olivier

    2016-01-01

    Negative autoregulation is universally found across organisms. In the bacterium Escherichia coli, transcription factors often repress their own expression to form a negative feedback network motif that enables robustness to changes in biochemical parameters. Here we present a simple phenomenological model of a negative feedback transcription factor repressing both itself and another target gene. The strength of the negative feedback is characterized by three parameters: the cooperativity in self-repression, the maximal expression rate of the transcription factor, and the apparent dissociation constant of the transcription factor binding to its own promoter. Analysis of the model shows that the target gene levels are robust to mutations in the transcription factor, and that the robustness improves as the degree of cooperativity in self-repression increases. The prediction is tested in the LexA transcriptional network of E. coli by altering cooperativity in self-repression and promoter strength. Indeed, we find robustness is correlated with the former. Considering the proposed importance of gene regulation in speciation, parameters governing a transcription factor’s robustness to mutation may have significant influence on a cell or organism’s capacity to evolve. PMID:27391757

  8. Cooperativity of Negative Autoregulation Confers Increased Mutational Robustness

    Science.gov (United States)

    Marciano, David C.; Lua, Rhonald C.; Herman, Christophe; Lichtarge, Olivier

    2016-06-01

    Negative autoregulation is universally found across organisms. In the bacterium Escherichia coli, transcription factors often repress their own expression to form a negative feedback network motif that enables robustness to changes in biochemical parameters. Here we present a simple phenomenological model of a negative feedback transcription factor repressing both itself and another target gene. The strength of the negative feedback is characterized by three parameters: the cooperativity in self-repression, the maximal expression rate of the transcription factor, and the apparent dissociation constant of the transcription factor binding to its own promoter. Analysis of the model shows that the target gene levels are robust to mutations in the transcription factor, and that the robustness improves as the degree of cooperativity in self-repression increases. The prediction is tested in the LexA transcriptional network of E. coli by altering cooperativity in self-repression and promoter strength. Indeed, we find robustness is correlated with the former. Considering the proposed importance of gene regulation in speciation, parameters governing a transcription factor's robustness to mutation may have significant influence on a cell or organism's capacity to evolve.

  9. Robust Image Watermarking using Fractional Sinc Transformation

    Directory of Open Access Journals (Sweden)

    Almas Abbasi

    2016-09-01

    Full Text Available The increased utilization of internet in sharing and dissemination of digital data makes it is very difficult to maintain copyright and ownership of data. Digital watermarking offers a method for authentication and copyright protection. Digital image watermarking is an important technique for the multimedia content authentication and copyright protection. This paper present a watermarking algorithm making a balance between imperceptibility and robustness based on fractional calculus and also a domain has constructed using fractional Sinc function (FSc. The FSc model the signal as polynomial for watermark embedding. Watermark is embedded in all the coefficients of the image. Cross correlation method based on Neyman-Pearson is used for watermark detection. Moreover fraction rotation expression has constructed to achieve rotation. Experimental results confirmed the proposed technique has good robustness and outperformed another technique in imperceptibility. Furthermore the proposed method enables blind watermark detection where the original image is not required during the watermark detection and thus making it more practical than non-blind watermarking techniques.

  10. Algebraic connectivity and graph robustness.

    Energy Technology Data Exchange (ETDEWEB)

    Feddema, John Todd; Byrne, Raymond Harry; Abdallah, Chaouki T. (University of New Mexico)

    2009-07-01

    Recent papers have used Fiedler's definition of algebraic connectivity to show that network robustness, as measured by node-connectivity and edge-connectivity, can be increased by increasing the algebraic connectivity of the network. By the definition of algebraic connectivity, the second smallest eigenvalue of the graph Laplacian is a lower bound on the node-connectivity. In this paper we show that for circular random lattice graphs and mesh graphs algebraic connectivity is a conservative lower bound, and that increases in algebraic connectivity actually correspond to a decrease in node-connectivity. This means that the networks are actually less robust with respect to node-connectivity as the algebraic connectivity increases. However, an increase in algebraic connectivity seems to correlate well with a decrease in the characteristic path length of these networks - which would result in quicker communication through the network. Applications of these results are then discussed for perimeter security.

  11. A Robust Streaming Media System

    Science.gov (United States)

    Youwei, Zhang

    Presently, application layer multicast protocols (ALM) are proposed as substitute for IP multicast and have made extraordinary achievements. Integrated with Multi-data-stream mode such as Multiple Description Coding (MDC), ALM becomes more scalable and robust in high-dynamic Internet environment compared with single data stream. Although MDC can provide a flexible data transmission style, the synchronization of different descriptions encoded from one video source is proved to be difficult due to different delay on diverse transmission paths. In this paper, an ALM system called HMDC is proposed to improve accepted video quality of streaming media, hosts can join the separate overlay trees in different layers simultaneously, then the maximum synchronized descriptions of the same layer are worked out to acquire the best video quality. Simulations implemented on Internet-like topology indicate that HMDC achieves better video quality, lower link stress, higher robustness and comparable latency compared with traditional ALM protocols.

  12. Robust estimation of Cronbach's alpha

    OpenAIRE

    2002-01-01

    Cronbach’s alpha is a popular method to measure reliability, e.g. in quantifying the reliability of a score to summarize the information of several items in questionnaires. The alpha coefficient is known to be non-robust. We study the behavior of this coefficient in different settings to identify situations, which can easily occur in practice, but under which the Cronbach’s alpha coefficient is extremely sensitive to violations of the classical model assumptions. Furthermore, we construct a r...

  13. Robust power system frequency control

    CERN Document Server

    Bevrani, Hassan

    2014-01-01

    This updated edition of the industry standard reference on power system frequency control provides practical, systematic and flexible algorithms for regulating load frequency, offering new solutions to the technical challenges introduced by the escalating role of distributed generation and renewable energy sources in smart electric grids. The author emphasizes the physical constraints and practical engineering issues related to frequency in a deregulated environment, while fostering a conceptual understanding of frequency regulation and robust control techniques. The resulting control strategi

  14. A robust adaptive robot controller

    OpenAIRE

    1993-01-01

    A globally convergent adaptive control scheme for robot motion control with the following features is proposed. First, the adaptation law possesses enhanced robustness with respect to noisy velocity measurements. Second, the controller does not require the inclusion of high gain loops that may excite the unmodeled dynamics and amplify the noise level. Third, we derive for the unknown parameter design a relationship between compensator gains and closed-loop convergence rates that is independen...

  15. Robust nonlinear regression in applications

    OpenAIRE

    Lim, Changwon; Sen, Pranab K.; Peddada, Shyamal D.

    2013-01-01

    Robust statistical methods, such as M-estimators, are needed for nonlinear regression models because of the presence of outliers/influential observations and heteroscedasticity. Outliers and influential observations are commonly observed in many applications, especially in toxicology and agricultural experiments. For example, dose response studies, which are routinely conducted in toxicology and agriculture, sometimes result in potential outliers, especially in the high dose gr...

  16. Parametric uncertainty modeling for robust control

    DEFF Research Database (Denmark)

    Rasmussen, K.H.; Jørgensen, Sten Bay

    1999-01-01

    The dynamic behaviour of a non-linear process can often be approximated with a time-varying linear model. In the presented methodology the dynamics is modeled non-conservatively as parametric uncertainty in linear lime invariant models. The obtained uncertainty description makes it possible...... method can be utilized in identification of a nominal model with uncertainty description. The method is demonstrated on a binary distillation column operating in the LV configuration. The dynamics of the column is approximated by a second order linear model, wherein the parameters vary as the operating...... to perform robustness analysis on a control system using the structured singular value. The idea behind the proposed method is to fit a rational function to the parameter variation. The parameter variation can then be expressed as a linear fractional transformation (LFT), It is discussed how the proposed...

  17. Cognitive Principles in Robust Multimodal Interpretation

    CERN Document Server

    Chai, J Y; Qu, S; 10.1613/jair.1936

    2011-01-01

    Multimodal conversational interfaces provide a natural means for users to communicate with computer systems through multiple modalities such as speech and gesture. To build effective multimodal interfaces, automated interpretation of user multimodal inputs is important. Inspired by the previous investigation on cognitive status in multimodal human machine interaction, we have developed a greedy algorithm for interpreting user referring expressions (i.e., multimodal reference resolution). This algorithm incorporates the cognitive principles of Conversational Implicature and Givenness Hierarchy and applies constraints from various sources (e.g., temporal, semantic, and contextual) to resolve references. Our empirical results have shown the advantage of this algorithm in efficiently resolving a variety of user references. Because of its simplicity and generality, this approach has the potential to improve the robustness of multimodal input interpretation.

  18. Congruent evolution of genetic and environmental robustness in microRNA

    CERN Document Server

    Szöll?si, Gergely J

    2008-01-01

    Genetic robustness, the preservation of an optimal phenotype in the face of mutations, is critical to the understanding of evolution as phenotypically expressed genetic variation is the fuel of natural selection. The origin of genetic robustness, whether it evolves directly by natural selection or it is a correlated byproduct of other phenotypic traits, is, however, unresolved. Examining microRNA (miRNA) genes of several eukaryotic species, Borenstein and Ruppin [PNAS 103:6593(2006)], showed that the structure of miRNA precursor stem-loops exhibits significantly increased mutational robustness in comparison with a sample of random RNA sequences with the same stem-loop structure. The observed robustness was found to be uncorrelated with traditional measures of environmental robustness -- implying that miRNA sequences show evidence of the direct evolution of genetic robustness. These findings are surprising as theoretical results indicate that the direct evolution of robustness requires high mutation rates and/...

  19. Robustness of multimodal processes itineraries

    DEFF Research Database (Denmark)

    Bocewicz, G.; Banaszak, Z.; Nielsen, Izabela Ewa

    2013-01-01

    This paper concerns multimodal transport systems (MTS) represented by a supernetworks in which several unimodal networks are connected by transfer links and focuses on the scheduling problems encountered in these systems. Assuming unimodal networks are modeled as cyclic lines, i.e. the routes det...... of multimodal processes driven itinerary planning problem is our main contribution. Illustrative examples providing alternative itineraries in some cases of MTS malfunction are presented....

  20. Prime-boost vaccination with Bacillus Calmette Guerin and a recombinant adenovirus co-expressing CFP10, ESAT6, Ag85A and Ag85B of Mycobacterium tuberculosis induces robust antigen-specific immune responses in mice.

    Science.gov (United States)

    Li, Wu; Li, Min; Deng, Guangcun; Zhao, Liping; Liu, Xiaoming; Wang, Yujiong

    2015-08-01

    Tuberculosis (TB) remains to be a prevalent health issue worldwide. At present, Mycobacterium bovis Bacillus Calmette Guerin (BCG) is the singular anti-TB vaccine available for the prevention of disease in humans; however, this vaccine only provides limited protection against Mycobacterium tuberculosis (Mtb) infection. Therefore, the development of alternative vaccines and strategies for increasing the efficacy of vaccination against TB are urgently required. The present study aimed to evaluate the ability of a recombinant adenoviral vector (Ad5-CEAB) co-expressing 10-kDa culture filtrate protein, 6-kDa early-secreted antigenic target, antigen 85 (Ag85)A and Ag85B of Mtb to boost immune responses following primary vaccination with BCG in mice. The mice were first subcutaneously primed with BCG and boosted with two doses of Ad5-CEAB via an intranasal route. The immunological effects of Ad5-CEAB boosted mice primed with BCG were then evaluated using a series of immunological indexes. The results demonstrated that the prime-boost strategy induced a potent antigen-specific immune response, which was primarily characterized by an enhanced T cell response and increased production of cytokines, including interferon-γ, tumor necrosis factor-α and interleukin-2, in mice. In addition, this vaccination strategy was demonstrated to have an elevated humoral response with increased concentrations of antigen-specific bronchoalveolar lavage secretory immunoglobulin (Ig)A and serum IgG in mice compared with those primed with BCG alone. These data suggested that the regimen of subcutaneous BCG prime and mucosal Ad5-CEAB boost was a novel strategy for inducing a broad range of antigen-specific immune responses to Mtb antigens in vivo, which may provide a promising strategy for further development of adenoviral-based vaccine against Mtb infection.

  1. Robustness in Railway Operations (RobustRailS)

    DEFF Research Database (Denmark)

    Jensen, Jens Parbo; Nielsen, Otto Anker

    This study considers the problem of enhancing railway timetable robustness without adding slack time, hence increasing the travel time. The approach integrates a transit assignment model to assess how passengers adapt their behaviour whenever operations are changed. First, the approach considers...... the existing stopping patterns of the railway lines. Then, based on the passenger demand we try to optimize the overall utility by changing the stopping pattern in a way that capacity utilization is reduced without affecting the frequency of the train lines nor increasing the passengers’ travel time....

  2. Robustness Analysis of Timber Truss Structure

    DEFF Research Database (Denmark)

    Rajčić, Vlatka; Čizmar, Dean; Kirkegaard, Poul Henning

    2010-01-01

    The present paper discusses robustness of structures in general and the robustness requirements given in the codes. Robustness of timber structures is also an issues as this is closely related to Working group 3 (Robustness of systems) of the COST E55 project. Finally, an example of a robustness...... evaluation of a widespan timber truss structure is presented. This structure was built few years ago near Zagreb and has a span of 45m. Reliability analysis of the main members and the system is conducted and based on this a robustness analysis is preformed....

  3. Synaptic Plasticity and NO-cGMP-PKG Signaling Coordinately Regulate ERK-Driven Gene Expression in the Lateral Amygdala and in the Auditory Thalamus Following Pavlovian Fear Conditioning

    Science.gov (United States)

    Ota, Kristie T.; Monsey, Melissa S.; Wu, Melissa S.; Young, Grace J.; Schafe, Glenn E.

    2010-01-01

    We have recently hypothesized that NO-cGMP-PKG signaling in the lateral nucleus of the amygdala (LA) during auditory fear conditioning coordinately regulates ERK-driven transcriptional changes in both auditory thalamic (MGm/PIN) and LA neurons that serve to promote pre- and postsynaptic alterations at thalamo-LA synapses, respectively. In the…

  4. Stochasticity in the Genotype-Phenotype Map: Implications for the Robustness and Persistence of Bet-Hedging

    Science.gov (United States)

    Nichol, Daniel; Robertson-Tessi, Mark; Jeavons, Peter; Anderson, Alexander R.A.

    2016-01-01

    Nongenetic variation in phenotypes, or bet-hedging, has been observed as a driver of drug resistance in both bacterial infections and cancers. Here, we study how bet-hedging emerges in genotype–phenotype (GP) mapping through a simple interaction model: a molecular switch. We use simple chemical reaction networks to implement stochastic switches that map gene products to phenotypes, and investigate the impact of structurally distinct mappings on the evolution of phenotypic heterogeneity. Bet-hedging naturally emerges within this model, and is robust to evolutionary loss through mutations to both the expression of individual genes, and to the network itself. This robustness explains an apparent paradox of bet-hedging—why does it persist in environments where natural selection necessarily acts to remove it? The structure of the underlying molecular mechanism, itself subject to selection, can slow the evolutionary loss of bet-hedging to ensure a survival mechanism against environmental catastrophes even when they are rare. Critically, these properties, taken together, have profound implications for the use of treatment-holidays to combat bet-hedging-driven resistant disease, as the efficacy of breaks from treatment will ultimately be determined by the structure of the GP mapping. PMID:27770034

  5. Undersampled face recognition via robust auxiliary dictionary learning.

    Science.gov (United States)

    Wei, Chia-Po; Wang, Yu-Chiang Frank

    2015-06-01

    In this paper, we address the problem of robust face recognition with undersampled training data. Given only one or few training images available per subject, we present a novel recognition approach, which not only handles test images with large intraclass variations such as illumination and expression. The proposed method is also to handle the corrupted ones due to occlusion or disguise, which is not present during training. This is achieved by the learning of a robust auxiliary dictionary from the subjects not of interest. Together with the undersampled training data, both intra and interclass variations can thus be successfully handled, while the unseen occlusions can be automatically disregarded for improved recognition. Our experiments on four face image datasets confirm the effectiveness and robustness of our approach, which is shown to outperform state-of-the-art sparse representation-based methods.

  6. Sustainable Resilient, Robust & Resplendent Enterprises

    DEFF Research Database (Denmark)

    Edgeman, Rick

    . Resilience may be regarded as enterprise ability to recover or rebound from negative shocks or extreme challenges to its ecosystem (Contu, 2002). Robustness, in contrast to resilience, is not so much enterprise ability to recover from shocks or challenges to its ecosystem, but rather resistance or immunity...... to their impact. Resplendent enterprises are introduced with resplendence referring not to some sort of public or private façade, but instead refers to organizations marked by dual brilliance and nobility of strategy, governance and comportment that yields superior and sustainable triple bottom line performance...

  7. Robustness Evaluation of Timber Structures

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Sørensen, John Dalsgaard; Cizmar, D.

    2010-01-01

    The present paper outlines results from working group 3 (WG3) in the EU COST Action E55 – ‘Modelling of the performance of timber structures’. The objectives of the project are related to the three main research activities: the identification and modelling of relevant load and environmental...... exposure scenarios, the improvement of knowledge concerning the behaviour of timber structural elements and the development of a generic framework for the assessment of the life-cycle vulnerability and robustness of timber structures....

  8. Robust and Sparse Factor Modelling

    DEFF Research Database (Denmark)

    Croux, Christophe; Exterkate, Peter

    Factor construction methods are widely used to summarize a large panel of variables by means of a relatively small number of representative factors. We propose a novel factor construction procedure that enjoys the properties of robustness to outliers and of sparsity; that is, having relatively few...... nonzero factor loadings. Compared to the traditional factor construction method, we find that this procedure leads to a favorable forecasting performance in the presence of outliers and to better interpretable factors. We investigate the performance of the method in a Monte Carlo experiment...

  9. Robust Adaptive Quantum Phase Estimation

    CERN Document Server

    Roy, Shibdas; Huntington, Elanor H

    2014-01-01

    Quantum parameter estimation is central to many fields such as quantum computation, communications and metrology. Optimal estimation theory has been instrumental in achieving the best accuracy in quantum parameter estimation, which is possible when we have very precise knowledge of and control over the model. However, uncertainties in key parameters underlying the system are unavoidable and may impact the quality of the estimate. We show here how quantum optical phase estimation of a squeezed state of light exhibits improvement when using a robust fixed-interval smoother designed with uncertainties explicitly introduced in parameters underlying the phase noise.

  10. Sustainable Resilient, Robust & Resplendent Enterprises

    DEFF Research Database (Denmark)

    Edgeman, Rick

    to their impact. Resplendent enterprises are introduced with resplendence referring not to some sort of public or private façade, but instead refers to organizations marked by dual brilliance and nobility of strategy, governance and comportment that yields superior and sustainable triple bottom line performance....... Herein resilience, robustness, and resplendence (R3) are integrated with sustainable enterprise excellence (Edgeman and Eskildsen, 2013) or SEE and social-ecological innovation (Eskildsen and Edgeman, 2012) to aid progress of a firm toward producing continuously relevant performance that proceed from...... continuously responsible strategy, behavior and other actions. A SEER3 model is introduced and a means of SEER3 maturity assessment is suggested....

  11. Progressive refinement for robust image registration

    Institute of Scientific and Technical Information of China (English)

    Li Song; Yuanhua Zhou; Jun Zhou

    2005-01-01

    @@ A new image registration algorithm with robust cost function and progressive refinement estimation is developed on the basis of direct method (DM). The robustness lies in M-estimation to avert larger local noise and outliers.

  12. Delay-induced driven patterns in coupled Cayley tree networks

    CERN Document Server

    Singh, Aradhana

    2013-01-01

    We study effects of delay in diffusively coupled logistic maps on the Cayley tree networks. We find that smaller coupling values exhibits sensitiveness for value of delay, and leads to different cluster patterns of self-organized and driven types. Whereas larger coupling strengths are very robust against change in delay values, and leads to stable driven clusters comprising only nodes from last generation of the Calaye tree. Furthermore, introduction of delay exhibits suppression as well as enhancement of synchronization depending upon coupling strength values, hence demonstrating richness of the model. To the end we relate the results with social conflicts and cooperation observed in families.

  13. The Driven Spinning Top

    Science.gov (United States)

    Grosu, Ioan; Featonby, David

    2016-01-01

    This driven top is quite a novelty and can, with some trials, be made using the principles outlined here. This new top has many applications in developing both understanding and skills and these are detailed in the article. Depending on reader's available time and motivation they may feel an urge to make one themselves, or simply invest a few…

  14. The Driven Spinning Top

    Science.gov (United States)

    Grosu, Ioan; Featonby, David

    2016-01-01

    This driven top is quite a novelty and can, with some trials, be made using the principles outlined here. This new top has many applications in developing both understanding and skills and these are detailed in the article. Depending on reader's available time and motivation they may feel an urge to make one themselves, or simply invest a few…

  15. Data-driven storytelling

    CERN Document Server

    Henry Riche, Nathalie

    2017-01-01

    This book is an accessible introduction to data-driven storytelling, resulting from discussions between data visualization researchers and data journalists. This book will be the first to define the topic, present compelling examples and existing resources, as well as identify challenges and new opportunities for research.

  16. Robust Instrumentation[Water treatment for power plant]; Robust Instrumentering

    Energy Technology Data Exchange (ETDEWEB)

    Wik, Anders [Vattenfall Utveckling AB, Stockholm (Sweden)

    2003-08-01

    Cementa Slite Power Station is a heat recovery steam generator (HRSG) with moderate steam data; 3.0 MPa and 420 deg C. The heat is recovered from Cementa, a cement industry, without any usage of auxiliary fuel. The Power station commenced operation in 2001. The layout of the plant is unusual, there are no similar in Sweden and very few world-wide, so the operational experiences are limited. In connection with the commissioning of the power plant a R and D project was identified with the objective to minimise the manpower needed for chemistry management of the plant. The lean chemistry management is based on robust instrumentation and chemical-free water treatment plant. The concept with robust instrumentation consists of the following components; choice of on-line instrumentation with a minimum of O and M and a chemical-free water treatment. The parameters are specific conductivity, cation conductivity, oxygen and pH. In addition to that, two fairly new on-line instruments were included; corrosion monitors and differential pH calculated from specific and cation conductivity. The chemical-free water treatment plant consists of softening, reverse osmosis and electro-deionisation. The operational experience shows that the cycle chemistry is not within the guidelines due to major problems with the operation of the power plant. These problems have made it impossible to reach steady state and thereby not viable to fully verify and validate the concept with robust instrumentation. From readings on the panel of the online analysers some conclusions may be drawn, e.g. the differential pH measurements have fulfilled the expectations. The other on-line analysers have been working satisfactorily apart from contamination with turbine oil, which has been noticed at least twice. The corrosion monitors seem to be working but the lack of trend curves from the mainframe computer system makes it hard to draw any clear conclusions. The chemical-free water treatment has met all

  17. On Robust H2 Estimation

    Institute of Scientific and Technical Information of China (English)

    Lihua Xie

    2005-01-01

    The problem of state estimation for uncertain systems has attracted a recurring interest in the past decade. In this paper, we shall give an overview on some of the recent development in the area by focusing on the robust H2 (Kaiman) filtering of uncertain discrete-time systems. The robust H2 estimation is concerned with the design of a fixed estimator for a family of plants under consideration such that the estimation error covariance is of a minimal upper bound. The uncertainty under consideration includes norm-bounded uncertainty and polytopic uncertainty. In the finite horizon case, we shall discuss a parameterized difference Riccati equation approach for systems with normbounded uncertainty and pinpoint the difference of state estimation between systems without uncertainty and those with uncertainty. In the infinite horizon case, we shall deal with both the norm-bounded and polytopic uncertainties using a linear matrix inequality (LMI) approach. In particular, we shall demonstrate how the conservatism of design can be improved using a slack variable technique. We also propose an iterative algorithm to refine a designed estimator. An example will be given to compare estimators designed using various techniques.

  18. Robust distributed cognitive relay beamforming

    KAUST Repository

    Pandarakkottilil, Ubaidulla

    2012-05-01

    In this paper, we present a distributed relay beamformer design for a cognitive radio network in which a cognitive (or secondary) transmit node communicates with a secondary receive node assisted by a set of cognitive non-regenerative relays. The secondary nodes share the spectrum with a licensed primary user (PU) node, and each node is assumed to be equipped with a single transmit/receive antenna. The interference to the PU resulting from the transmission from the cognitive nodes is kept below a specified limit. The proposed robust cognitive relay beamformer design seeks to minimize the total relay transmit power while ensuring that the transceiver signal-to-interference- plus-noise ratio and PU interference constraints are satisfied. The proposed design takes into account a parameter of the error in the channel state information (CSI) to render the performance of the beamformer robust in the presence of imperfect CSI. Though the original problem is non-convex, we show that the proposed design can be reformulated as a tractable convex optimization problem that can be solved efficiently. Numerical results are provided and illustrate the performance of the proposed designs for different network operating conditions and parameters. © 2012 IEEE.

  19. A ROBUST OPTICAL FLOW COMPUTATION

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This paper presents a new method for robust and accurate optical flow estimation. The significance of this work is twofold. Firstly, the idea of bi-directional scheme is adopted to reduce the model error of optical flow equation, which allows the second order Taylor's expansion of optical flow equation for accurate solution without much extra computational burden; Secondly, this paper establishs a new optical flow equation based on LSCM (Local Structure Constancy Model) instead of BCM (Brightness Constancy Model), namely the optical flow equation does not act on scalar but on tensor-valued (matrix-valued) field, due to the two reason: (1) structure tensor-value contains local spatial structure information, which provides us more useable cues for computation than scalar; (2) local image structure is less sensitive to illumination variation than intensity, which weakens the disturbance of non-uniform illumination in real sequences. Qualitative and quantitative results for synthetic and real-world scenes show that the new method can produce an accurate and robust results.

  20. Robust Inflation from Fibrous Strings

    CERN Document Server

    Burgess, C P; de Alwis, S; Quevedo, F

    2016-01-01

    Successful inflationary models should (i) describe the data well; (ii) arise generically from sensible UV completions; (iii) be insensitive to detailed fine-tunings of parameters and (iv) make interesting new predictions. We argue that a class of models with these properties is characterized by relatively simple potentials with a constant term and negative exponentials. We here continue earlier work exploring UV completions for these models, including the key (though often ignored) issue of modulus stabilisation, to assess the robustness of their predictions. We show that string models where the inflaton is a fibration modulus seem to be robust due to an effective rescaling symmetry, and fairly generic since most known Calabi-Yau manifolds are fibrations. This class of models is characterized by a generic relation between the tensor-to-scalar ratio $r$ and the spectral index $n_s$ of the form $r \\propto (n_s -1)^2$ where the proportionality constant depends on the nature of the effects used to develop the inf...

  1. Robust Inflation from fibrous strings

    Science.gov (United States)

    Burgess, C. P.; Cicoli, M.; de Alwis, S.; Quevedo, F.

    2016-05-01

    Successful inflationary models should (i) describe the data well; (ii) arise generically from sensible UV completions; (iii) be insensitive to detailed fine-tunings of parameters and (iv) make interesting new predictions. We argue that a class of models with these properties is characterized by relatively simple potentials with a constant term and negative exponentials. We here continue earlier work exploring UV completions for these models—including the key (though often ignored) issue of modulus stabilisation—to assess the robustness of their predictions. We show that string models where the inflaton is a fibration modulus seem to be robust due to an effective rescaling symmetry, and fairly generic since most known Calabi-Yau manifolds are fibrations. This class of models is characterized by a generic relation between the tensor-to-scalar ratio r and the spectral index ns of the form r propto (ns-1)2 where the proportionality constant depends on the nature of the effects used to develop the inflationary potential and the topology of the internal space. In particular we find that the largest values of the tensor-to-scalar ratio that can be obtained by generalizing the original set-up are of order r lesssim 0.01. We contrast this general picture with specific popular models, such as the Starobinsky scenario and α-attractors. Finally, we argue the self consistency of large-field inflationary models can strongly constrain non-supersymmetric inflationary mechanisms.

  2. Robust Inflation from fibrous strings

    Energy Technology Data Exchange (ETDEWEB)

    Burgess, C.P. [Department of Physics & Astronomy, McMaster University,1280 Main Street West, Hamilton ON (Canada); Perimeter Institute for Theoretical Physics,31 Caroline Street North, Waterloo ON (Canada); Cicoli, M. [Dipartimento di Fisica e Astronomia, Università di Bologna,via Irnerio 46, 40126 Bologna (Italy); INFN, Sezione di Bologna, Bologna (Italy); Abdus Salam International Center for Theoretical Physics,Strada Costiera 11, Trieste 34014 (Italy); Alwis, S. de [Physics Department, University of Colorado,Boulder, CO 80309 (United States); Quevedo, F. [Abdus Salam International Center for Theoretical Physics,Strada Costiera 11, Trieste 34014 (Italy); DAMTP, University of Cambridge,Wilberforce Road, Cambridge, CB3 0WA (United Kingdom)

    2016-05-13

    Successful inflationary models should (i) describe the data well; (ii) arise generically from sensible UV completions; (iii) be insensitive to detailed fine-tunings of parameters and (iv) make interesting new predictions. We argue that a class of models with these properties is characterized by relatively simple potentials with a constant term and negative exponentials. We here continue earlier work exploring UV completions for these models — including the key (though often ignored) issue of modulus stabilisation — to assess the robustness of their predictions. We show that string models where the inflaton is a fibration modulus seem to be robust due to an effective rescaling symmetry, and fairly generic since most known Calabi-Yau manifolds are fibrations. This class of models is characterized by a generic relation between the tensor-to-scalar ratio r and the spectral index n{sub s} of the form r∝(n{sub s}−1){sup 2} where the proportionality constant depends on the nature of the effects used to develop the inflationary potential and the topology of the internal space. In particular we find that the largest values of the tensor-to-scalar ratio that can be obtained by generalizing the original set-up are of order r≲0.01. We contrast this general picture with specific popular models, such as the Starobinsky scenario and α-attractors. Finally, we argue the self consistency of large-field inflationary models can strongly constrain non-supersymmetric inflationary mechanisms.

  3. Robust design of NLF airfoils

    Institute of Scientific and Technical Information of China (English)

    Li Jing; Gao Zhenghong; Huang Jiangtao; Zhao Ke

    2013-01-01

    A robust optimization design approach of natural laminar airfoils is developed in this paper.First,the non-uniform rational B-splines (NURBS) free form deformation method based on NURBS basis function is introduced to the airfoil parameterization.Second,aerodynamic characteristics are evaluated by solving Navier Stokes equations,and the γ-Reθt transition model coupling with shear-stress transport (SST) turbulent model is introduced to simulate boundary layer transition.A numerical simulation of transition flow around NLF0416 airfoil is conducted to test the code.The comparison between numerical simulation results and wind tunnel test data approves the validity and applicability of the present transition model.Third,the optimization system is set up,which uses the separated particle swarm optimization (SPSO) as search algorithm and combines the Kriging models as surrogate model during optimization.The system is applied to carry out robust design about the uncertainty of lift coefficient and Mach number for NASA NLF-0115 airfoil.The data of optimized airfoil aerodynamic characteristics indicates that the optimized airfoil can maintain laminar flow stably in an uncertain range and has a wider range of low drag.

  4. Robust portfolio selection under norm uncertainty

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2016-06-01

    Full Text Available Abstract In this paper, we consider the robust portfolio selection problem which has a data uncertainty described by the ( p , w $(p,w$ -norm in the objective function. We show that the robust formulation of this problem is equivalent to a linear optimization problem. Moreover, we present some numerical results concerning our robust portfolio selection problem.

  5. Robust synchronization of uncertain chaotic systems

    Institute of Scientific and Technical Information of China (English)

    Li Fang; Hu Ai-Hua; Xu Zheng-Yuan

    2006-01-01

    This paper investigates robust unified (lag, anticipated, and complete) synchronization of two coupled chaotic systems. By introducing the concepts of positive definite symmetrical matrix and Riccati inequality and the theory of robust stability, several criteria on robust synchronization are established. Extensive numerical simulations are also used to confirm the results.

  6. Methodology in robust and nonparametric statistics

    CERN Document Server

    Jurecková, Jana; Picek, Jan

    2012-01-01

    Introduction and SynopsisIntroductionSynopsisPreliminariesIntroductionInference in Linear ModelsRobustness ConceptsRobust and Minimax Estimation of LocationClippings from Probability and Asymptotic TheoryProblemsRobust Estimation of Location and RegressionIntroductionM-EstimatorsL-EstimatorsR-EstimatorsMinimum Distance and Pitman EstimatorsDifferentiable Statistical FunctionsProblemsAsymptotic Representations for L-Estimators

  7. No tradeoff between versatility and robustness in gene circuit motifs

    Science.gov (United States)

    Payne, Joshua L.

    2016-05-01

    Circuit motifs are small directed subgraphs that appear in real-world networks significantly more often than in randomized networks. In the Boolean model of gene circuits, most motifs are realized by multiple circuit genotypes. Each of a motif's constituent circuit genotypes may have one or more functions, which are embodied in the expression patterns the circuit forms in response to specific initial conditions. Recent enumeration of a space of nearly 17 million three-gene circuit genotypes revealed that all circuit motifs have more than one function, with the number of functions per motif ranging from 12 to nearly 30,000. This indicates that some motifs are more functionally versatile than others. However, the individual circuit genotypes that constitute each motif are less robust to mutation if they have many functions, hinting that functionally versatile motifs may be less robust to mutation than motifs with few functions. Here, I explore the relationship between versatility and robustness in circuit motifs, demonstrating that functionally versatile motifs are robust to mutation despite the inherent tradeoff between versatility and robustness at the level of an individual circuit genotype.

  8. Multiplexed and robust representations of sound features in auditory cortex.

    Science.gov (United States)

    Walker, Kerry M M; Bizley, Jennifer K; King, Andrew J; Schnupp, Jan W H

    2011-10-12

    We can recognize the melody of a familiar song when it is played on different musical instruments. Similarly, an animal must be able to recognize a warning call whether the caller has a high-pitched female or a lower-pitched male voice, and whether they are sitting in a tree to the left or right. This type of perceptual invariance to "nuisance" parameters comes easily to listeners, but it is unknown whether or how such robust representations of sounds are formed at the level of sensory cortex. In this study, we investigate whether neurons in both core and belt areas of ferret auditory cortex can robustly represent the pitch, formant frequencies, or azimuthal location of artificial vowel sounds while the other two attributes vary. We found that the spike rates of the majority of cortical neurons that are driven by artificial vowels carry robust representations of these features, but the most informative temporal response windows differ from neuron to neuron and across five auditory cortical fields. Furthermore, individual neurons can represent multiple features of sounds unambiguously by independently modulating their spike rates within distinct time windows. Such multiplexing may be critical to identifying sounds that vary along more than one perceptual dimension. Finally, we observed that formant information is encoded in cortex earlier than pitch information, and we show that this time course matches ferrets' behavioral reaction time differences on a change detection task.

  9. A Robust Sound Perception Model Suitable for Neuromorphic Implementation

    Directory of Open Access Journals (Sweden)

    Martin eCoath

    2014-01-01

    Full Text Available We have recently demonstrated the emergence of dynamic feature sensitivity through exposure to formative stimuli in a real-time neuromorphic system implementing a hybrid analogue/digital network of spiking neurons. This network, inspired by models of auditory processing in mammals, includes several mutually connected layers with distance-dependent transmission delays and learning in the form of spike timing dependent plasticity, which effects stimulus-driven changes in the network connectivity.Here we present results that demonstrate that the network is robust to a range of variations in the stimulus pattern, such as are found in naturalistic stimuli and neural responses. This robustness is a property critical to the development of realistic, electronic neuromorphic systems.We analyse the variability of the response of the network to `noisy' stimuli which allows us to characterize the acuity in information-theoretic terms. This provides an objective basis for the quantitative comparison of networks, their connectivity patterns, and learning strategies, which can inform future design decisions. We also show, using stimuli derived from speech samples, that the principles are robust to other challenges, such as variable presentation rate, that would have to be met by systems deployed in the real world. Finally we demonstrate the potential applicability of the approach to real sounds.

  10. What cycles the cell? -Robust autonomous cell cycle models.

    Science.gov (United States)

    Lavi, Orit; Louzoun, Yoram

    2009-12-01

    The cell cycle is one of the best studied cellular mechanisms at the experimental and theoretical levels. Although most of the important biochemical components and reactions of the cell cycle are probably known, the precise way the cell cycle dynamics are driven is still under debate. This phenomenon is not atypical to many other biological systems where the knowledge of the molecular building blocks and the interactions between them does not lead to a coherent picture of the appropriate dynamics. We here propose a methodology to develop plausible models for the driving mechanisms of embryonic and cancerous cell cycles. We first define a key property of the system (a cyclic behaviour in the case of the embryonic cell cycle) and set mathematical constraints on the types of two variable simplified systems robustly reproducing such a cyclic behaviour. We then expand these robust systems to three variables and reiterate the procedure. At each step, we further limit the type of expanded systems to fit the known microbiology until a detailed description of the system is obtained. This methodology produces mathematical descriptions of the required biological systems that are more robust to changes in the precise function and rate constants. This methodology can be extended to practically any type of subcellular mechanism.

  11. Fluctuation relations for a driven Brownian particle

    Science.gov (United States)

    Imparato, A.; Peliti, L.

    2006-08-01

    We consider a driven Brownian particle, subject to both conservative and nonconservative applied forces, whose probability evolves according to the Kramers equation. We derive a general fluctuation relation, expressing the ratio of the probability of a given Brownian path in phase space with that of the time-reversed path, in terms of the entropy flux to the heat reservoir. This fluctuation relation implies those of Seifert, Jarzynski, and Gallavotti-Cohen in different special cases.

  12. Robust PCA via Outlier Pursuit

    CERN Document Server

    Xu, Huan; Sanghavi, Sujay

    2010-01-01

    Singular Value Decomposition (and Principal Component Analysis) is one of the most widely used techniques for dimensionality reduction: successful and efficiently computable, it is nevertheless plagued by a well-known, well-documented sensitivity to outliers. Recent work has considered the setting where each point has a few arbitrarily corrupted components. Yet, in applications of SVD or PCA such as robust collaborative filtering or bioinformatics, malicious agents, defective genes, or simply corrupted or contaminated experiments may effectively yield entire points that are completely corrupted. We present an efficient convex optimization-based algorithm we call Outlier Pursuit, that under some mild assumptions on the uncorrupted points (satisfied, e.g., by the standard generative assumption in PCA problems) recovers the exact optimal low-dimensional subspace, and identifies the corrupted points. Such identification of corrupted points that do not conform to the low-dimensional approximation, is of paramount ...

  13. Neutral Evolution of Mutational Robustness

    CERN Document Server

    Van Nimwegen, E; Huynen, M; Nimwegen, Erik van; Crutchfield, James P.; Huynen, Martijn

    1999-01-01

    We introduce and analyze a general model of a population evolving over a network of selectively neutral genotypes. We show that the population's limit distribution on the neutral network is solely determined by the network topology and given by the principal eigenvector of the network's adjacency matrix. Moreover, the average number of neutral mutant neighbors per individual is given by the matrix spectral radius. This quantifies the extent to which populations evolve mutational robustness: the insensitivity of the phenotype to mutations. Since the average neutrality is independent of evolutionary parameters---such as, mutation rate, population size, and selective advantage---one can infer global statistics of neutral network topology using simple population data available from {\\it in vitro} or {\\it in vivo} evolution. Populations evolving on neutral networks of RNA secondary structures show excellent agreement with our theoretical predictions.

  14. Quantifying robustness of biochemical network models

    Directory of Open Access Journals (Sweden)

    Iglesias Pablo A

    2002-12-01

    Full Text Available Abstract Background Robustness of mathematical models of biochemical networks is important for validation purposes and can be used as a means of selecting between different competing models. Tools for quantifying parametric robustness are needed. Results Two techniques for describing quantitatively the robustness of an oscillatory model were presented and contrasted. Single-parameter bifurcation analysis was used to evaluate the stability robustness of the limit cycle oscillation as well as the frequency and amplitude of oscillations. A tool from control engineering – the structural singular value (SSV – was used to quantify robust stability of the limit cycle. Using SSV analysis, we find very poor robustness when the model's parameters are allowed to vary. Conclusion The results show the usefulness of incorporating SSV analysis to single parameter sensitivity analysis to quantify robustness.

  15. Electrically driven optical antennas

    Science.gov (United States)

    Kern, Johannes; Kullock, René; Prangsma, Jord; Emmerling, Monika; Kamp, Martin; Hecht, Bert

    2015-09-01

    Unlike radiowave antennas, so far optical nanoantennas cannot be fed by electrical generators. Instead, they are driven by light or indirectly via excited discrete states in active materials in their vicinity. Here we demonstrate the direct electrical driving of an in-plane optical antenna by the broadband quantum-shot noise of electrons tunnelling across its feed gap. The spectrum of the emitted photons is determined by the antenna geometry and can be tuned via the applied voltage. Moreover, the direction and polarization of the light emission are controlled by the antenna resonance, which also improves the external quantum efficiency by up to two orders of magnitude. The one-material planar design offers facile integration of electrical and optical circuits and thus represents a new paradigm for interfacing electrons and photons at the nanometre scale, for example for on-chip wireless communication and highly configurable electrically driven subwavelength photon sources.

  16. Test-driven programming

    Science.gov (United States)

    Georgiev, Bozhidar; Georgieva, Adriana

    2013-12-01

    In this paper, are presented some possibilities concerning the implementation of a test-driven development as a programming method. Here is offered a different point of view for creation of advanced programming techniques (build tests before programming source with all necessary software tools and modules respectively). Therefore, this nontraditional approach for easier programmer's work through building tests at first is preferable way of software development. This approach allows comparatively simple programming (applied with different object-oriented programming languages as for example JAVA, XML, PYTHON etc.). It is predictable way to develop software tools and to provide help about creating better software that is also easier to maintain. Test-driven programming is able to replace more complicated casual paradigms, used by many programmers.

  17. Affinity driven social networks

    Science.gov (United States)

    Ruyú, B.; Kuperman, M. N.

    2007-04-01

    In this work we present a model for evolving networks, where the driven force is related to the social affinity between individuals of a population. In the model, a set of individuals initially arranged on a regular ordered network and thus linked with their closest neighbors are allowed to rearrange their connections according to a dynamics closely related to that of the stable marriage problem. We show that the behavior of some topological properties of the resulting networks follows a non trivial pattern.

  18. Expressiveness and Robustness of First-Price Position Auctions

    OpenAIRE

    Dütting, Paul; Fischer, Felix; Parkes, David C.

    2013-01-01

    Since economic mechanisms are often applied to very different instances of the same problem, it is desirable to identify mechanisms that work well in a wide range of circumstances. We pursue this goal for a position auction setting and specifically seek mechanisms that guarantee good outcomes under both complete and incomplete information. A variant of the generalized first-price mechanism with multi-dimensional bids turns out to be the only standard mechanism able to achieve this goal, even ...

  19. NSCLC Driven by DDR2 Mutation Is Sensitive to Dasatinib and JQ1 Combination Therapy.

    Science.gov (United States)

    Xu, Chunxiao; Buczkowski, Kevin A; Zhang, Yanxi; Asahina, Hajime; Beauchamp, Ellen M; Terai, Hideki; Li, Yvonne Y; Meyerson, Matthew; Wong, Kwok-Kin; Hammerman, Peter S

    2015-10-01

    Genetically engineered mouse models of lung cancer have demonstrated an important role in understanding the function of novel lung cancer oncogenes and tumor-suppressor genes identified in genomic studies of human lung cancer. Furthermore, these models are important platforms for preclinical therapeutic studies. Here, we generated a mouse model of lung adenocarcinoma driven by mutation of the discoidin domain receptor 2 (DDR2) gene combined with loss of TP53. DDR2(L63V);TP53(L/L) mice developed poorly differentiated lung adenocarcinomas in all transgenic animals analyzed with a latency of 40 to 50 weeks and a median survival of 67.5 weeks. Mice expressing wild-type DDR2 with combined TP53 loss did not form lung cancers. DDR2(L63V);TP53(L/L) tumors displayed robust expression of DDR2 and immunohistochemical markers of lung adenocarcinoma comparable with previously generated models, though also displayed concomitant expression of the squamous cell markers p63 and SOX2. Tumor-derived cell lines were not solely DDR2 dependent and displayed upregulation of and partial dependence on MYCN. Combined treatment with the multitargeted DDR2 inhibitor dasatinib and BET inhibitor JQ1 inhibited tumor growth in vitro and in vivo. Together, these results suggest that DDR2 mutation can drive lung cancer initiation in vivo and provide a novel mouse model for lung cancer therapeutics studies.

  20. Expression of human AR cDNA driven by its own promoter results in mild promotion, but not suppression, of growth in human prostate cancer PC-3 cells%自身启动子驱动的人雄激素受体cDNA的表达能够适度促进而不是抑制人前列腺癌细胞PC-3的生长

    Institute of Scientific and Technical Information of China (English)

    Saleh Altuwaijri; Cheng-Chia Wu; Yuan-Jie Niu; Atsushi Mizokami; Hong-Chiang Chang; Chawnshang Chang

    2007-01-01

    Aim: To examine the physiological role of the androgen receptor (AR) in the PC-3 cell line by transfecting full-length functional AR cDNA driven by its natural human AR promoter. Methods: We generated an AR-expressing PC-3(AR)9 stable clone that expresses AR under the control of the natural human AR promoter and compared its proliferation to that of the PC-3(AR)2 (stable clone that expresses AR under the control of the cytomegalovirus (CMV) promoter,established by Heisler et al.) after androgen treatment. Results: We found that dihydrotestosterone (DHT) from 0.001 nmol/L to 10 nmol/L induces cell cycle arrest or inhibits proliferation of PC-3(AR)2 compared with its vector control, PC-3(pIRES). In contrast, PC-3(AR)9 cell growth slightly increased or did not change when treated with physiological concentrations of 1 nmol/L DHT. Conclusion: These data suggest that intracellular control of AR expression levels through the natural AR promoter might be needed for determining AR function in androgen-independent prostate cancer (AIPC) PC-3 cells. Unlike previous publications that showed DHT mediated suppression of PC-3 growth after transfection of viral promoter-driven AR overexpression, we report here that DHT-mediated PC-3 proliferation is slightly induced or does not change compared with its baseline after reintroducing AR expression driven by its own natural promoter, as shown in PC-3(AR)9 prostate cancer cells.

  1. Building Robust Systems with Fallible Construction (Elaboration de systemes informatiques robustes a l’architecutre faillible)

    Science.gov (United States)

    2008-04-01

    IST-047 Building Robust Systems with Fallible Construction (Elaboration de systèmes informatiques robustes à l’architecture faillible) Final...IST-047 Building Robust Systems with Fallible Construction (Elaboration de systèmes informatiques robustes à l’architecture faillible...and cost investments. ES - 2 RTO-TR-IST-047 Elaboration de systèmes informatiques robustes à l’architecture faillible (RTO-TR-IST-047

  2. Performance of a grid-connected wind generation system with a robust susceptance controller

    Energy Technology Data Exchange (ETDEWEB)

    Rahim, A.H.M.A. [Department of Electrical Engineering, K.F. University of Petroleum and Minerals, KFUPM Box 349, Dhahran 31261 (Saudi Arabia); Nowicki, E.P. [Department of Electrical and Computer Engineering, University of Calgary, Calgary, AB (Canada)

    2011-01-15

    Wind turbine driven induction generators are vulnerable to transient disturbances like wind gusts and low voltages on the system. The fixed capacitor at the generator terminal or the limited support from the grid may not be able to provide the requisite reactive power under these abnormal conditions. This paper presents a susceptance control strategy for a variable speed wound-rotor induction generator which can cater for the reactive power requirement. The susceptance is adjusted through a robust feedback controller included in the terminal voltage driven automatic excitation control circuit. The fixed parameter robust controller design is carried out in frequency domain using multiplicative uncertainty modeling and H{sub {infinity}} norms. The robustness of the controller has been evaluated through optimally tuned PID controllers. Simulation results show that the robust controller can effectively restore normal operation following emergencies like sudden load changes, wind gusts and low voltage conditions. The proposed robust controller has been shown to have adequate fault ride through capabilities in order to be able to meet connection requirements defined by transmission system operators. (author)

  3. Robust Topology Optimization of Truss with regard to Volume

    CERN Document Server

    Mohr, Daniel P; Matzies, Thomas; Knapek, Christina A

    2011-01-01

    A common problem in the optimization of structures is the handling of uncertainties in the parameters. If the parameters appear in the constraints, the uncertainties can lead to an infinite number of constraints. Usually the constraints have to be approximated by finite expressions to generate a computable problem. Here, using the example of the topology optimization of a truss, a method is proposed to deal with such uncertainties by using robust optimization techniques, leading to an approach without the necessity of any approximation. With adequately chosen load cases, the final expression is equivalent to the multiple load case. Simple numerical examples of typical problems illustrate the application of the method.

  4. β-Defensin 2 is a responsive biomarker of IL-17A-driven skin pathology in patients with psoriasis.

    Science.gov (United States)

    Kolbinger, Frank; Loesche, Christian; Valentin, Marie-Anne; Jiang, Xiaoyu; Cheng, Yi; Jarvis, Philip; Peters, Thomas; Calonder, Claudio; Bruin, Gerard; Polus, Florine; Aigner, Birgit; Lee, David M; Bodenlenz, Manfred; Sinner, Frank; Pieber, Thomas Rudolf; Patel, Dhavalkumar D

    2017-03-01

    IL-17A is a key driver of human autoimmune diseases, particularly psoriasis. We sought to determine the role of IL-17A in psoriasis pathogenesis and to identify a robust and measurable biomarker of IL-17A-driven pathology. We studied 8 healthy subjects and 8 patients with psoriasis before and after administration of secukinumab, a fully human anti-IL-17A mAb, and used a combination of classical techniques and a novel skin microperfusion assay to evaluate the expression of 170 proteins in blood, nonlesional skin, and lesional skin. For validation, we also tested stored sera from 601 patients with a variety of autoimmune diseases. IL-17A was specifically expressed in lesional compared with nonlesional psoriatic skin (9.8 vs 0.8 pg/mL, P psoriasis versus that in healthy subjects (5746 vs 82 pg/mL in serum, P psoriasis, BD-2 levels correlated well with IL-17A levels (r = 0.70, n = 199, P Psoriasis Area and Severity Index scores (r = 0.53, n = 281, P psoriasis, and serum BD-2 is an easily measurable biomarker of IL-17A-driven skin pathology. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Application of Bounded Linear Stability Analysis Method for Metrics-Driven Adaptive Control

    Science.gov (United States)

    Bakhtiari-Nejad, Maryam; Nguyen, Nhan T.; Krishnakumar, Kalmanje

    2009-01-01

    This paper presents the application of Bounded Linear Stability Analysis (BLSA) method for metrics-driven adaptive control. The bounded linear stability analysis method is used for analyzing stability of adaptive control models, without linearizing the adaptive laws. Metrics-driven adaptive control introduces a notion that adaptation should be driven by some stability metrics to achieve robustness. By the application of bounded linear stability analysis method the adaptive gain is adjusted during the adaptation in order to meet certain phase margin requirements. Analysis of metrics-driven adaptive control is evaluated for a second order system that represents a pitch attitude control of a generic transport aircraft. The analysis shows that the system with the metrics-conforming variable adaptive gain becomes more robust to unmodeled dynamics or time delay. The effect of analysis time-window for BLSA is also evaluated in order to meet the stability margin criteria.

  6. Quantifying the robustness of metro networks

    CERN Document Server

    Wang, Xiangrong; Derrible, Sybil; Ahmad, Sk Nasir; Kooij, Robert E

    2015-01-01

    Metros (heavy rail transit systems) are integral parts of urban transportation systems. Failures in their operations can have serious impacts on urban mobility, and measuring their robustness is therefore critical. Moreover, as physical networks, metros can be viewed as network topological entities, and as such they possess measurable network properties. In this paper, by using network science and graph theoretical concepts, we investigate both theoretical and experimental robustness metrics (i.e., the robustness indicator, the effective graph conductance, and the critical thresholds) and their performance in quantifying the robustness of metro networks under random failures or targeted attacks. We find that the theoretical metrics quantify different aspects of the robustness of metro networks. In particular, the robustness indicator captures the number of alternative paths and the effective graph conductance focuses on the length of each path. Moreover, the high positive correlation between the theoretical m...

  7. A network property necessary for concentration robustness

    Science.gov (United States)

    Eloundou-Mbebi, Jeanne M. O.; Küken, Anika; Omranian, Nooshin; Kleessen, Sabrina; Neigenfind, Jost; Basler, Georg; Nikoloski, Zoran

    2016-10-01

    Maintenance of functionality of complex cellular networks and entire organisms exposed to environmental perturbations often depends on concentration robustness of the underlying components. Yet, the reasons and consequences of concentration robustness in large-scale cellular networks remain largely unknown. Here, we derive a necessary condition for concentration robustness based only on the structure of networks endowed with mass action kinetics. The structural condition can be used to design targeted experiments to study concentration robustness. We show that metabolites satisfying the necessary condition are present in metabolic networks from diverse species, suggesting prevalence of this property across kingdoms of life. We also demonstrate that our predictions about concentration robustness of energy-related metabolites are in line with experimental evidence from Escherichia coli. The necessary condition is applicable to mass action biological systems of arbitrary size, and will enable understanding the implications of concentration robustness in genetic engineering strategies and medical applications.

  8. Robust AIC with High Breakdown Scale Estimate

    Directory of Open Access Journals (Sweden)

    Shokrya Saleh

    2014-01-01

    Full Text Available Akaike Information Criterion (AIC based on least squares (LS regression minimizes the sum of the squared residuals; LS is sensitive to outlier observations. Alternative criterion, which is less sensitive to outlying observation, has been proposed; examples are robust AIC (RAIC, robust Mallows Cp (RCp, and robust Bayesian information criterion (RBIC. In this paper, we propose a robust AIC by replacing the scale estimate with a high breakdown point estimate of scale. The robustness of the proposed methods is studied through its influence function. We show that, the proposed robust AIC is effective in selecting accurate models in the presence of outliers and high leverage points, through simulated and real data examples.

  9. Towards Robust Image Matching Algorithms

    Science.gov (United States)

    Parsons, Timothy J.

    1984-12-01

    The rapid advance in digital electronics during recent years has enabled the real-time hardware implementation of many basic image processing techniques and these methods are finding increasing use in both commercial and military applications where a superiority to existing systems can be demonstrated. The potential superiority of an entirely passive, automatic image processing based navigation system over the less accurate and active navigation systems based on radar, for example "TERCOM", is evident. By placing a sensor on board an aircraft or missile together with the appropriate processing power and enough memory to store a reference image or a map of the planned route, large scale features extracted from the scene available to the sensor can be compared with the same feature stored in memory. The difference between the aircraft's actual position and its desired position can then be evaluated and the appropriate navigational correction undertaken. This paper summaries work carried out at British Aerospace Hatfield to investigate various classes of algorithms and solutions which would render a robust image matching system viable for such an automatic system flying at low level with a thermal I.R. sensor.

  10. Designing for Reliability and Robustness

    Science.gov (United States)

    Svetlik, Randall G.; Moore, Cherice; Williams, Antony

    2017-01-01

    Long duration spaceflight has a negative effect on the human body, and exercise countermeasures are used on-board the International Space Station (ISS) to minimize bone and muscle loss, combatting these effects. Given the importance of these hardware systems to the health of the crew, this equipment must continue to be readily available. Designing spaceflight exercise hardware to meet high reliability and availability standards has proven to be challenging throughout the time the crewmembers have been living on ISS beginning in 2000. Furthermore, restoring operational capability after a failure is clearly time-critical, but can be problematic given the challenges of troubleshooting the problem from 220 miles away. Several best-practices have been leveraged in seeking to maximize availability of these exercise systems, including designing for robustness, implementing diagnostic instrumentation, relying on user feedback, and providing ample maintenance and sparing. These factors have enhanced the reliability of hardware systems, and therefore have contributed to keeping the crewmembers healthy upon return to Earth. This paper will review the failure history for three spaceflight exercise countermeasure systems identifying lessons learned that can help improve future systems. Specifically, the Treadmill with Vibration Isolation and Stabilization System (TVIS), Cycle Ergometer with Vibration Isolation and Stabilization System (CEVIS), and the Advanced Resistive Exercise Device (ARED) will be reviewed, analyzed, and conclusions identified so as to provide guidance for improving future exercise hardware designs. These lessons learned, paired with thorough testing, offer a path towards reduced system down-time.

  11. Efficient robust conditional random fields.

    Science.gov (United States)

    Song, Dongjin; Liu, Wei; Zhou, Tianyi; Tao, Dacheng; Meyer, David A

    2015-10-01

    Conditional random fields (CRFs) are a flexible yet powerful probabilistic approach and have shown advantages for popular applications in various areas, including text analysis, bioinformatics, and computer vision. Traditional CRF models, however, are incapable of selecting relevant features as well as suppressing noise from noisy original features. Moreover, conventional optimization methods often converge slowly in solving the training procedure of CRFs, and will degrade significantly for tasks with a large number of samples and features. In this paper, we propose robust CRFs (RCRFs) to simultaneously select relevant features. An optimal gradient method (OGM) is further designed to train RCRFs efficiently. Specifically, the proposed RCRFs employ the l1 norm of the model parameters to regularize the objective used by traditional CRFs, therefore enabling discovery of the relevant unary features and pairwise features of CRFs. In each iteration of OGM, the gradient direction is determined jointly by the current gradient together with the historical gradients, and the Lipschitz constant is leveraged to specify the proper step size. We show that an OGM can tackle the RCRF model training very efficiently, achieving the optimal convergence rate [Formula: see text] (where k is the number of iterations). This convergence rate is theoretically superior to the convergence rate O(1/k) of previous first-order optimization methods. Extensive experiments performed on three practical image segmentation tasks demonstrate the efficacy of OGM in training our proposed RCRFs.

  12. Nanotechnology Based Environmentally Robust Primers

    Energy Technology Data Exchange (ETDEWEB)

    Barbee, T W Jr; Gash, A E; Satcher, J H Jr; Simpson, R L

    2003-03-18

    An initiator device structure consisting of an energetic metallic nano-laminate foil coated with a sol-gel derived energetic nano-composite has been demonstrated. The device structure consists of a precision sputter deposition synthesized nano-laminate energetic foil of non-toxic and non-hazardous metals along with a ceramic-based energetic sol-gel produced coating made up of non-toxic and non-hazardous components such as ferric oxide and aluminum metal. Both the nano-laminate and sol-gel technologies are versatile commercially viable processes that allow the ''engineering'' of properties such as mechanical sensitivity and energy output. The nano-laminate serves as the mechanically sensitive precision igniter and the energetic sol-gel functions as a low-cost, non-toxic, non-hazardous booster in the ignition train. In contrast to other energetic nanotechnologies these materials can now be safely manufactured at application required levels, are structurally robust, have reproducible and engineerable properties, and have excellent aging characteristics.

  13. Robust growth of Escherichia coli.

    Science.gov (United States)

    Wang, Ping; Robert, Lydia; Pelletier, James; Dang, Wei Lien; Taddei, Francois; Wright, Andrew; Jun, Suckjoon

    2010-06-22

    The quantitative study of the cell growth has led to many fundamental insights in our understanding of a wide range of subjects, from the cell cycle to senescence. Of particular importance is the growth rate, whose constancy represents a physiological steady state of an organism. Recent studies, however, suggest that the rate of elongation during exponential growth of bacterial cells decreases cumulatively with replicative age for both asymmetrically and symmetrically dividing organisms, implying that a "steady-state" population consists of individual cells that are never in a steady state of growth. To resolve this seeming paradoxical observation, we studied the long-term growth and division patterns of Escherichia coli cells by employing a microfluidic device designed to follow steady-state growth and division of a large number of cells at a defined reproductive age. Our analysis of approximately 10(5) individual cells reveals a remarkable stability of growth whereby the mother cell inherits the same pole for hundreds of generations. We further show that death of E. coli is not purely stochastic but is the result of accumulating damages. We conclude that E. coli, unlike all other aging model systems studied to date, has a robust mechanism of growth that is decoupled from cell death.

  14. User-Driven Innovation: An Exploratory Study

    Directory of Open Access Journals (Sweden)

    Blanka Tacer

    2015-03-01

    Full Text Available Despite the relatively robust promotion of user-driven innovation (UDI in practice, research on UDI remains in its early stages. Following a grounded theory analysis approach, this paper makes a contribution by conducting exploratory research of the field. Nine interviews yield an empirical basis for extracting categories connected with existing conceptual issues. The results reveal three key elements of the UDI (user involvement, searching for feedback, and design orientation. The results also indicate the interdisciplinary nature of UDI with branding, design, and company-user interaction as complementary fields in creating user experience. The analysis leads to four theoretical propositions for future studies. The article concludes with limitations and implications for future research.

  15. Robust video foreground segmentation and face recognition

    Institute of Scientific and Technical Information of China (English)

    GUAN Ye-peng

    2009-01-01

    Face recognition provides a natural visual interface for human computer interaction (HCI) applications.The process of face recognition,however,is inhibited by variations in the appearance of face images caused by changes in lighting,expression,viewpoint,aging and introduction of occlusion.Although various algorithms have been presented for face recognition,face recognition is still a very challenging topic.A novel approach of real time face recognition for HCI is proposed in the paper.In view of the limits of the popular approaches to foreground segmentation,wavelet multi-scale transform based background subtraction is developed to extract foreground objects.The optimal selection of the threshold is automatically determined,which does not require any complex supervised training or manual experimental calibration.A robust real time face recognition algorithm is presented,which combines the projection matrixes without iteration and kernel Fisher discriminant analysis (KFDA) to overcome some difficulties existing in the real face recognition.Superior performance of the proposed algorithm is demonstrated by comparing with other algorithms through experiments.The proposed algorithm can also be applied to the video image sequences of natural HCI.

  16. Nonlinear Robust Control for Spacecraft Attitude

    Directory of Open Access Journals (Sweden)

    Wang Lina

    2013-07-01

    Full Text Available Nonlinear robust control of the spacecraft attitude with the existence of external disturbances is considered. A robust attitude controller is designed based on the passivity approach the quaternion representation, which introduces the suppression vector of external disturbance into the control law and does not need angular velocity measurement. Stability conditions of the robust attitude controller are given. And the numerical simulation results show the effectiveness of the attitude controller.

  17. Robust chaos in smooth unimodal maps

    Science.gov (United States)

    Andrecut, M.; Ali, M. K.

    2001-08-01

    Robust chaos is defined by the absence of periodic windows and coexisting attractors in some neighborhood of the parameter space. It has been conjectured that robust chaos cannot occur in smooth systems [E. Barreto, B. Hunt, and C. Grebogi, Phys. Rev. Lett. 78, 4561 (1997); 80, 3049 (1998)]. Contrary to this conjecture, we describe a general procedure for generating robust chaos in smooth unimodal maps.

  18. Robustness of timber structures in seismic areas

    OpenAIRE

    Neves, Luís A.C.; Branco, Jorge M.

    2011-01-01

    Major similarities between robustness assessment and seismic design exist, and significant information can be brought from seismic design to robustness design. As will be discussed, although some methods and limitations considered in seismic design can improve robustness, the capacity of the structure to sustain limited damage without disproportionate effects is significantly more complex. In fact, seismic design can either improve or reduce the resistance of structures to unfo...

  19. Constellations-driven innovation

    DEFF Research Database (Denmark)

    Hansbøl, Mikala

    2013-01-01

    The paper presents a science and technology studies and actor-network-theory inspired approach to understanding the development and ongoing re-didactication and re-design of a Danish developed presentation tool called the Theme Board (Tematavlen.dk). It is argued that this approach provides a par...... a particularly useful point of departure for engaging in researching innovation and didactic design of digital teaching and learning instruments such as the Theme Board that are programmed and serviced 'in the sky'. I call this approach: constellation-driven innovations....

  20. Electrostatically Driven Nanoballoon Actuator.

    Science.gov (United States)

    Barzegar, Hamid Reza; Yan, Aiming; Coh, Sinisa; Gracia-Espino, Eduardo; Dunn, Gabriel; Wågberg, Thomas; Louie, Steven G; Cohen, Marvin L; Zettl, Alex

    2016-11-09

    We demonstrate an inflatable nanoballoon actuator based on geometrical transitions between the inflated (cylindrical) and collapsed (flattened) forms of a carbon nanotube. In situ transmission electron microscopy experiments employing a nanoelectromechanical manipulator show that a collapsed carbon nanotube can be reinflated by electrically charging the nanotube, thus realizing an electrostatically driven nanoballoon actuator. We find that the tube actuator can be reliably cycled with only modest control voltages (few volts) with no apparent wear or fatigue. A complementary theoretical analysis identifies critical parameters for nanotube nanoballoon actuation.

  1. Robust Linear Models for Cis-eQTL Analysis.

    Directory of Open Access Journals (Sweden)

    Mattias Rantalainen

    Full Text Available Expression Quantitative Trait Loci (eQTL analysis enables characterisation of functional genetic variation influencing expression levels of individual genes. In outbread populations, including humans, eQTLs are commonly analysed using the conventional linear model, adjusting for relevant covariates, assuming an allelic dosage model and a Gaussian error term. However, gene expression data generally have noise that induces heavy-tailed errors relative to the Gaussian distribution and often include atypical observations, or outliers. Such departures from modelling assumptions can lead to an increased rate of type II errors (false negatives, and to some extent also type I errors (false positives. Careful model checking can reduce the risk of type-I errors but often not type II errors, since it is generally too time-consuming to carefully check all models with a non-significant effect in large-scale and genome-wide studies. Here we propose the application of a robust linear model for eQTL analysis to reduce adverse effects of deviations from the assumption of Gaussian residuals. We present results from a simulation study as well as results from the analysis of real eQTL data sets. Our findings suggest that in many situations robust models have the potential to provide more reliable eQTL results compared to conventional linear models, particularly in respect to reducing type II errors due to non-Gaussian noise. Post-genomic data, such as that generated in genome-wide eQTL studies, are often noisy and frequently contain atypical observations. Robust statistical models have the potential to provide more reliable results and increased statistical power under non-Gaussian conditions. The results presented here suggest that robust models should be considered routinely alongside other commonly used methodologies for eQTL analysis.

  2. Transcriptional robustness and protein interactions are associated in yeast

    Directory of Open Access Journals (Sweden)

    Conant Gavin C

    2011-05-01

    Full Text Available Abstract Background Robustness to insults, both external and internal, is a characteristic feature of life. One level of biological organization for which noise and robustness have been extensively studied is gene expression. Cells have a variety of mechanisms for buffering noise in gene expression, but it is not completely clear what rules govern whether or not a given gene uses such tools to maintain appropriate expression. Results Here, we show a general association between the degree to which yeast cells have evolved mechanisms to buffer changes in gene expression and whether they possess protein-protein interactions. We argue that this effect bears an affinity to epistasis, because yeast appears to have evolved regulatory mechanisms such that distant changes in gene copy number for a protein-protein interaction partner gene can alter a gene's expression. This association is not unexpected given recent work linking epistasis and the deleterious effects of changes in gene dosage (i.e., the dosage balance hypothesis. Using gene expression data from artificial aneuploid strains of bakers' yeast, we found that genes coding for proteins that physically interact with other proteins show less expression variation in response to aneuploidy than do other genes. This effect is even more pronounced for genes whose products interact with proteins encoded on aneuploid chromosomes. We further found that genes targeted by transcription factors encoded on aneuploid chromosomes were more likely to change in expression after aneuploidy. Conclusions We suggest that these observations can be best understood as resulting from the higher fitness cost of misexpression in epistatic genes and a commensurate greater regulatory control of them.

  3. Identification of uncertain nonlinear systems for robust fuzzy control.

    Science.gov (United States)

    Senthilkumar, D; Mahanta, Chitralekha

    2010-01-01

    In this paper, we consider fuzzy identification of uncertain nonlinear systems in Takagi-Sugeno (T-S) form for the purpose of robust fuzzy control design. The uncertain nonlinear system is represented using a fuzzy function having constant matrices and time varying uncertain matrices that describe the nominal model and the uncertainty in the nonlinear system respectively. The suggested method is based on linear programming approach and it comprises the identification of the nominal model and the bounds of the uncertain matrices and then expressing the uncertain matrices into uncertain norm bounded matrices accompanied by constant matrices. It has been observed that our method yields less conservative results than the other existing method proposed by Skrjanc et al. (2005). With the obtained fuzzy model, we showed the robust stability condition which provides a basis for different robust fuzzy control design. Finally, different simulation examples are presented for identification and control of uncertain nonlinear systems to illustrate the utility of our proposed identification method for robust fuzzy control.

  4. Optimizing the robustness of electrical power systems against cascading failures.

    Science.gov (United States)

    Zhang, Yingrui; Yağan, Osman

    2016-06-21

    Electrical power systems are one of the most important infrastructures that support our society. However, their vulnerabilities have raised great concern recently due to several large-scale blackouts around the world. In this paper, we investigate the robustness of power systems against cascading failures initiated by a random attack. This is done under a simple yet useful model based on global and equal redistribution of load upon failures. We provide a comprehensive understanding of system robustness under this model by (i) deriving an expression for the final system size as a function of the size of initial attacks; (ii) deriving the critical attack size after which system breaks down completely; (iii) showing that complete system breakdown takes place through a first-order (i.e., discontinuous) transition in terms of the attack size; and (iv) establishing the optimal load-capacity distribution that maximizes robustness. In particular, we show that robustness is maximized when the difference between the capacity and initial load is the same for all lines; i.e., when all lines have the same redundant space regardless of their initial load. This is in contrast with the intuitive and commonly used setting where capacity of a line is a fixed factor of its initial load.

  5. Endothelial cell-driven regulation of CD9 or motility-related protein-1 expression in multiple myeloma cells within the murine 5T33MM model and myeloma patients

    DEFF Research Database (Denmark)

    De Bruyne, E; Levin Andersen, Thomas; De Raeve, H;

    2006-01-01

    The cell surface expression of CD9, a glycoprotein of the tetraspanin family influencing several processes including cell motility and metastasis, inversely correlates with progression in several solid tumors. In the present work, we studied the expression and role of CD9 in multiple myeloma (MM)...... interaction of the cells with BMEC and that CD9 is involved in transendothelial invasion, thus possibly mediating homing and/or spreading of the MM cells........ These findings were also confirmed by immunohistochemistry in MM patients. Neutralizing anti-CD9 antibodies inhibited transendothelial invasion of CD9-expressing human MM5.1 and murine 5T33MMvivo cells. In conclusion, we provide evidence that CD9 expression by the MM cells is upregulated in vivo by close...

  6. Heat driven pulse pump

    Science.gov (United States)

    Benner, Steve M (Inventor); Martins, Mario S. (Inventor)

    2000-01-01

    A heat driven pulse pump includes a chamber having an inlet port, an outlet port, two check valves, a wick, and a heater. The chamber may include a plurality of grooves inside wall of the chamber. When heated within the chamber, a liquid to be pumped vaporizes and creates pressure head that expels the liquid through the outlet port. As liquid separating means, the wick, disposed within the chamber, is to allow, when saturated with the liquid, the passage of only liquid being forced by the pressure head in the chamber, preventing the vapor from exiting from the chamber through the outlet port. A plurality of grooves along the inside surface wall of the chamber can sustain the liquid, which is amount enough to produce vapor for the pressure head in the chamber. With only two simple moving parts, two check valves, the heat driven pulse pump can effectively function over the long lifetimes without maintenance or replacement. For continuous flow of the liquid to be pumped a plurality of pumps may be connected in parallel.

  7. Improved optically driven microrotors

    Science.gov (United States)

    Asavei, Theodor; Loke, Vincent L. Y.; Nieminen, Timo A.; Heckenberg, Norman R.; Rubinsztein-Dunlop, Halina

    2008-08-01

    Two-photon polymerization of optically curing resins is a powerful method to fabricate micron sized objects which can be used as tools to measure properties at small scales. These microdevices can be driven by means of externally applied focused laser beams (optical tweezers) through angular momentum exchange, giving rise to a net torque. The advantage of the optical drive is that no contact is required, therefore making the microdevices suited to non-invasive biological applications. The fabrication method is versatile and allows building objects of any 3D shape. We discuss the design and modelling of various optically driven rotors. In particular, we consider fabrication of microspheres with an internal shape birefringence in order to obtain rotation in an optical trap. The reason for fabricating this type of object is that they are well-suited for studies of mechanical properties of single biomolecules such as the torsional stiffness of DNA or torque generated by molecular motors. The microspheres fabricated are able to transduce torques of 2000 pNnm with optical powers of 500 mW and could be rotated with frequencies up to 40 Hz in circularly polarized light.

  8. Ubiquitous expression of the rtTA2S-M2 inducible system in transgenic mice driven by the human hnRNPA2B1/CBX3 CpG island

    Directory of Open Access Journals (Sweden)

    Antoniou Michael

    2007-09-01

    Full Text Available Abstract Background A sensitive, ubiquitously expressed tetracycline inducible system would be a valuable tool in mouse transgenesis. However, this has been difficult to obtain due to position effects observed at different chromosomal sites of transgene integration, which negatively affect expression in many tissues. The aim of this study was to test the utility of a mammalian methylation-free CpG island to drive ubiquitous expression of the sensitive doxycycline (Dox inducible rtTA2S-M2 Tet-transactivator in transgenic mice. Results An 8 kb genomic fragment from the methylation-free CpG island of the human hnRNPA2B1-CBX3 housekeeping gene locus was tested. In a number of transgenic mouse lines obtained, rtTA2S-M2 expression was detected in many tissues examined. Characterisation of the highest expressing rtTA2S-M2 transgenic mouse line demonstrated Dox-inducible GFP transgene expression in many tissues. Using this line we also show highly sensitive quantitative induction with low doses of Dox of an assayable plasma protein transgene under the control of a Tet Responsive Element (TRE. The utility of this rtTA2S-M2 line for inducible expression in mouse embryos was also demonstrated using a GATA-6 Tet-inducible transgene to show specific phenotypes in the embryonic lung, as well as broader effects resulting from the inducible widespread overexpression of the transgene. Conclusion The ubiquitously expressing rtTA2S-M2 transgenic mouse line described here provides a very useful tool for studying the effects of the widespread, inducible overexpression of genes during embryonic development and in adult mice.

  9. Noise and robustness in phyllotaxis.

    Science.gov (United States)

    Mirabet, Vincent; Besnard, Fabrice; Vernoux, Teva; Boudaoud, Arezki

    2012-01-01

    A striking feature of vascular plants is the regular arrangement of lateral organs on the stem, known as phyllotaxis. The most common phyllotactic patterns can be described using spirals, numbers from the Fibonacci sequence and the golden angle. This rich mathematical structure, along with the experimental reproduction of phyllotactic spirals in physical systems, has led to a view of phyllotaxis focusing on regularity. However all organisms are affected by natural stochastic variability, raising questions about the effect of this variability on phyllotaxis and the achievement of such regular patterns. Here we address these questions theoretically using a dynamical system of interacting sources of inhibitory field. Previous work has shown that phyllotaxis can emerge deterministically from the self-organization of such sources and that inhibition is primarily mediated by the depletion of the plant hormone auxin through polarized transport. We incorporated stochasticity in the model and found three main classes of defects in spiral phyllotaxis--the reversal of the handedness of spirals, the concomitant initiation of organs and the occurrence of distichous angles--and we investigated whether a secondary inhibitory field filters out defects. Our results are consistent with available experimental data and yield a prediction of the main source of stochasticity during organogenesis. Our model can be related to cellular parameters and thus provides a framework for the analysis of phyllotactic mutants at both cellular and tissular levels. We propose that secondary fields associated with organogenesis, such as other biochemical signals or mechanical forces, are important for the robustness of phyllotaxis. More generally, our work sheds light on how a target pattern can be achieved within a noisy background.

  10. Noise and robustness in phyllotaxis.

    Directory of Open Access Journals (Sweden)

    Vincent Mirabet

    Full Text Available A striking feature of vascular plants is the regular arrangement of lateral organs on the stem, known as phyllotaxis. The most common phyllotactic patterns can be described using spirals, numbers from the Fibonacci sequence and the golden angle. This rich mathematical structure, along with the experimental reproduction of phyllotactic spirals in physical systems, has led to a view of phyllotaxis focusing on regularity. However all organisms are affected by natural stochastic variability, raising questions about the effect of this variability on phyllotaxis and the achievement of such regular patterns. Here we address these questions theoretically using a dynamical system of interacting sources of inhibitory field. Previous work has shown that phyllotaxis can emerge deterministically from the self-organization of such sources and that inhibition is primarily mediated by the depletion of the plant hormone auxin through polarized transport. We incorporated stochasticity in the model and found three main classes of defects in spiral phyllotaxis--the reversal of the handedness of spirals, the concomitant initiation of organs and the occurrence of distichous angles--and we investigated whether a secondary inhibitory field filters out defects. Our results are consistent with available experimental data and yield a prediction of the main source of stochasticity during organogenesis. Our model can be related to cellular parameters and thus provides a framework for the analysis of phyllotactic mutants at both cellular and tissular levels. We propose that secondary fields associated with organogenesis, such as other biochemical signals or mechanical forces, are important for the robustness of phyllotaxis. More generally, our work sheds light on how a target pattern can be achieved within a noisy background.

  11. Noise and Robustness in Phyllotaxis

    Science.gov (United States)

    Mirabet, Vincent; Besnard, Fabrice; Vernoux, Teva; Boudaoud, Arezki

    2012-01-01

    A striking feature of vascular plants is the regular arrangement of lateral organs on the stem, known as phyllotaxis. The most common phyllotactic patterns can be described using spirals, numbers from the Fibonacci sequence and the golden angle. This rich mathematical structure, along with the experimental reproduction of phyllotactic spirals in physical systems, has led to a view of phyllotaxis focusing on regularity. However all organisms are affected by natural stochastic variability, raising questions about the effect of this variability on phyllotaxis and the achievement of such regular patterns. Here we address these questions theoretically using a dynamical system of interacting sources of inhibitory field. Previous work has shown that phyllotaxis can emerge deterministically from the self-organization of such sources and that inhibition is primarily mediated by the depletion of the plant hormone auxin through polarized transport. We incorporated stochasticity in the model and found three main classes of defects in spiral phyllotaxis – the reversal of the handedness of spirals, the concomitant initiation of organs and the occurrence of distichous angles – and we investigated whether a secondary inhibitory field filters out defects. Our results are consistent with available experimental data and yield a prediction of the main source of stochasticity during organogenesis. Our model can be related to cellular parameters and thus provides a framework for the analysis of phyllotactic mutants at both cellular and tissular levels. We propose that secondary fields associated with organogenesis, such as other biochemical signals or mechanical forces, are important for the robustness of phyllotaxis. More generally, our work sheds light on how a target pattern can be achieved within a noisy background. PMID:22359496

  12. ROBUST REPETITIVE CONTROL FOR IMPROVING RATE SMOOTHNESS OF TEST TURNTABLE

    Institute of Scientific and Technical Information of China (English)

    LIUYu; ZENGMing; SUBao-ku

    2005-01-01

    A robust repetitive control scheme is used to improve the rate smoothness of a brushless DC motor (BLDCM) driven test turntable. The method synthesizes variable structure control (VSC) laws and repetitive control (RC) laws in a complementary manner. The VSC strategy can stabilize the system and suppress uncertainties, such as the aperiodic disturbance and noises, while RC strategy can eliminate the periodic rate fluctuation in a steady state. The convergence of the repetitive learning process is also guaranteed by VSC. A general nonlinear system model is discussed. The model can be considered as an extension of BLDCMs. The stability and asymptotic position tracking performance are validated by using Lyapunov functions. Simulation results show the effectiveness of the proposed approach for improving the rate smoothness.

  13. A Robust Response of the Hadley Circulation to Global Warming

    Science.gov (United States)

    Lau, William K M.; Kim, Kyu-Myong

    2014-01-01

    Tropical rainfall is expected to increase in a warmer climate. Yet, recent studies have inferred that the Hadley Circulation (HC), which is primarily driven by latent heating from tropical rainfall, is weakened under global warming. Here, we show evidence of a robust intensification of the HC from analyses of 33 CMIP5 model projections under a scenario of 1 per year CO2 emission increase. The intensification is manifested in a deep-tropics squeeze, characterized by a pronounced increase in the zonal mean ascending motion in the mid and upper troposphere, a deepening and narrowing of the convective zone and enhanced rainfall in the deep tropics. These changes occur in conjunction with a rise in the region of maximum outflow of the HC, with accelerated meridional mass outflow in the uppermost branch of the HC away from the equator, coupled to a weakened inflow in the return branches of the HC in the lower troposphere.

  14. Robust chimera states in SQUID metamaterials with local interactions

    Science.gov (United States)

    Hizanidis, J.; Lazarides, N.; Tsironis, G. P.

    2016-09-01

    We report on the emergence of robust multiclustered chimera states in a dissipative-driven system of symmetrically and locally coupled identical superconducting quantum interference device (SQUID) oscillators. The "snakelike" resonance curve of the single SQUID is the key to the formation of the chimera states and is responsible for the extreme multistability exhibited by the coupled system that leads to attractor crowding at the geometrical resonance (inductive-capacitive) frequency. Until now, chimera states were mostly believed to exist for nonlocal coupling. Our findings provide theoretical evidence that nearest-neighbor interactions are indeed capable of supporting such states in a wide parameter range. SQUID metamaterials are the subject of intense experimental investigations, and we are highly confident that the complex dynamics demonstrated in this paper can be confirmed in the laboratory.

  15. Pressure driven flow in porous tubular membranes

    Science.gov (United States)

    Tilton, Nils; Martinand, Denis; Serre, Eric; Lueptow, Richard

    2011-11-01

    We consider the steady laminar flow of a Newtonian incompressible fluid in a porous tubular membrane with pressure-driven transmembrane flow. Due to its fundamental importance to membrane filtration systems, this flow has been studied extensively both analytically and numerically, yet a robust analytic solution has not been found. The problem is challenging due to the coupling between the transmembrane pressure and velocity with the simultaneous coupling between the axial pressure gradient and the axial velocity. We present a robust analytical solution which incorporates Darcy's law on the membrane surface. The solution is in the form of an asymptotic expansion about a small parameter related to the membrane permeability. We verify the analytical solution with comparison to 2-D spectral direct numerical simulations of ultrafiltration and microfiltration systems with typical operating conditions, as well as extreme cases of cross-flow reversal and axial flow exhaustion. In all cases, the agreement between the analytical and numerical results is excellent. Finally, we use the analytical and numerical results to provide guidelines about when common simplifying assumptions about the permeate flow may be made. Specifically, the assumptions of a parabolic axial velocity profile and uniform transmembrane velocity are valid only for small permeabilities.

  16. A Model-Driven Probabilistic Parser Generator

    CERN Document Server

    Quesada, Luis; Cortijo, Francisco J

    2012-01-01

    Existing probabilistic scanners and parsers impose hard constraints on the way lexical and syntactic ambiguities can be resolved. Furthermore, traditional grammar-based parsing tools are limited in the mechanisms they allow for taking context into account. In this paper, we propose a model-driven tool that allows for statistical language models with arbitrary probability estimators. Our work on model-driven probabilistic parsing is built on top of ModelCC, a model-based parser generator, and enables the probabilistic interpretation and resolution of anaphoric, cataphoric, and recursive references in the disambiguation of abstract syntax graphs. In order to prove the expression power of ModelCC, we describe the design of a general-purpose natural language parser.

  17. ESTIMATION OF GRASPING TORQUE USING ROBUST REACTION TORQUE OBSERVER FOR ROBOTIC FORCEPS

    OpenAIRE

    塚本, 祐介; Tsukamoto, Yusuke

    2015-01-01

    Abstract— In this paper, the estimation of the grasping torque of robotic forceps without the use of a force/torque sensor is discussed. To estimate the grasping torque when the robotic forceps driven by a rotary motor with a reduction gear grasps an object, a novel robust reaction torque observer is proposed. In the case where a conventional reaction force/torque observer is applied, the estimated torque includes not only the grasping torque, namely the reaction torque, but also t...

  18. Data-driven computational mechanics

    CERN Document Server

    Kirchdoerfer, Trenton

    2015-01-01

    We develop a new computing paradigm, which we refer to as data-driven computing, according to which calculations are carried out directly from experimental material data and pertinent constraints and conservation laws, such as compatibility and equilibrium, thus bypassing the empirical material modeling step of conventional computing altogether. Data-driven solvers seek to assign to each material point the state from a prespecified data set that is closest to satisfying the conservation laws. Equivalently, data-driven solvers aim to find the state satisfying the conservation laws that is closest to the data set. The resulting data-driven problem thus consists of the minimization of a distance function to the data set in phase space subject to constraints introduced by the conservation laws. We motivate the data-driven paradigm and investigate the performance of data-driven solvers by means of two examples of application, namely, the static equilibrium of nonlinear three-dimensional trusses and linear elastici...

  19. A 3D interactive multi-object segmentation tool using local robust statistics driven active contours

    OpenAIRE

    Gao, Yi; Kikinis, Ron; Bouix, Sylvain; Shenton, Martha Elizabeth; Tannenbaum, Allen

    2012-01-01

    Extracting anatomical and functional significant structures renders one of the important tasks for both the theoretical study of the medical image analysis, and the clinical and practical community. In the past, much work has been dedicated only to the algorithmic development. Nevertheless, for clinical end users, a well designed algorithm with an interactive software is necessary for an algorithm to be utilized in their daily work. Furthermore, the software would better be open sourced in or...

  20. Security and robustness for collaborative monitors

    NARCIS (Netherlands)

    Testerink, Bas; Bulling, Nils; Dastani, Mehdi

    2016-01-01

    Decentralized monitors can be subject to robustness and security risks. Robustness risks include attacks on the monitor’s infrastructure in order to disable parts of its functionality. Security risks include attacks that try to extract information from the monitor and thereby possibly leak sensitive

  1. Robustness of Long Span Reciprocal Timber Structures

    DEFF Research Database (Denmark)

    Balfroid, Nathalie; Kirkegaard, Poul Henning; Sassone, Mario SASSONE

    2011-01-01

    engineer may take necessary steps to design robust structures that are insensitive to accidental circumstances. The present paper makes a discussion of such robustness issues related to the future development of reciprocal timber structures. The paper concludes that these kind of structures can have...

  2. Robust fabric substrates for photonic textile applications

    NARCIS (Netherlands)

    Van Pieterson, L.; Bouten, P.C.P.; Kriege, J.C.; Bhattacharya, R.

    2010-01-01

    A fabric substrate is described for electronic textile with robust interwoven connections between the conductive yarns in it. The fabric's robustness, as a function of the electrical reliability of its conductive yarn connections, is shown to hold over large deformations.This fabric is then used to

  3. Robust fabric substrates for photonic textile applications

    NARCIS (Netherlands)

    Van Pieterson, L.; Bouten, P.C.P.; Kriege, J.C.; Bhattacharya, R.

    2010-01-01

    A fabric substrate is described for electronic textile with robust interwoven connections between the conductive yarns in it. The fabric's robustness, as a function of the electrical reliability of its conductive yarn connections, is shown to hold over large deformations.This fabric is then used to

  4. Robust identification for rational fractional transfer functions

    Institute of Scientific and Technical Information of China (English)

    王书宁

    1997-01-01

    An algorithm is proposed for robust identification of a rational fractional transfer function with a fixed degree under the framework of worst-case/deterministic robust identification. The convergence of the algorithm is proven. Its feasibility is shown with a numerical example.

  5. An Implementation Technique for Multivariate Robust Design

    Institute of Scientific and Technical Information of China (English)

    MA Yi-zhong; ZHAO Feng-yu

    2005-01-01

    This paper investigates systematically the problem of multivariate robust parameter design. First, a measurement criterion for the total variation of multivariate quality characteristics is introduced by the result of information theory. Then the implementation procedure in the robust design is presented. After that, a simulation example from a practical industrial process is provided. Finally, some comments and further work are discussed.

  6. Robust dissipativity for uncertain impulsive dynamical systems

    Directory of Open Access Journals (Sweden)

    Liu Bin

    2003-01-01

    Full Text Available We discuss the robust dissipativity with respect to the quadratic supply rate for uncertain impulsive dynamical systems. By employing the Hamilton-Jacobi inequality approach, some sufficient conditions of robust dissipativity for this kind of system are established. Finally, we specialize the obtained results to the case of uncertain linear impulsive dynamical systems.

  7. A Novel Robust Adaptive Fuzzy Controller

    Institute of Scientific and Technical Information of China (English)

    LIU Xiao-hua; WANG Xiu-hong; FEN En-min

    2002-01-01

    For a class of continuous-time nonlinear system, a novel robust adaptive fuzzy controller is proposed by using of Lyapunov method. It is proven that the control algorithm is globally stable, the output tracking-error can convergence to a domain of zero under the assumptions. As a result, the system controlled has stronger robustness for disturbance and modeling error.

  8. Extending the Scope of Robust Quadratic Optimization

    NARCIS (Netherlands)

    Marandi, Ahmadreza; Ben-Tal, A.; den Hertog, Dick; Melenberg, Bertrand

    2017-01-01

    In this paper, we derive tractable reformulations of the robust counterparts of convex quadratic and conic quadratic constraints with concave uncertainties for a broad range of uncertainty sets. For quadratic constraints with convex uncertainty, it is well-known that the robust counterpart is, in ge

  9. Security and robustness for collaborative monitors

    NARCIS (Netherlands)

    Testerink, Bas; Bulling, Nils; Dastani, Mehdi

    2016-01-01

    Decentralized monitors can be subject to robustness and security risks. Robustness risks include attacks on the monitor’s infrastructure in order to disable parts of its functionality. Security risks include attacks that try to extract information from the monitor and thereby possibly leak sensitive

  10. What is it to be sturdy (robust)?

    DEFF Research Database (Denmark)

    Nielsen, Niss Skov; Zwisler, Lars Pagter; Bojsen, Ann Kristina Mikkelsen;

    2015-01-01

    Purpose: This paper intends to give a first insight into the concept of being "sturdy/robust"; To develop and test a Danish model of how to measure sturdi-ness/robustness; To test the scale's ability to identify people in emergency situa-tions who have high risk of developing psychological illness....

  11. Non-probabilistic Robust Optimal Design Method

    Institute of Scientific and Technical Information of China (English)

    SUN Wei; XU Huanwei; ZHANG Xu

    2009-01-01

    For the purpose of dealing with uncertainty factors in engineering optimization problems, this paper presents a new non-probabilistic robust optimal design method based on maximum variation estimation. The method analyzes the effect of uncertain factors to objective and constraints functions, and then the maximal variations to a solution are calculated. In order to guarantee robust feasibility the maximal variations of constraints are added to original constraints as penalty term; the maximal variation of objective function is taken as a robust index to a solution; linear physical programming is used to adjust the values of quality characteristic and quality variation, and then a bi-level mathematical robust optimal model is coustructed. The method does not require presumed probability distribution of uncertain factors or continuous and differentiable of objective and constraints functions. To demonstrate the proposed method, the design of the two-bar structure acted by concentrated load is presented. In the example the robustness of the normal stress, feasibility of the total volume and the buckling stress are studied. The robust optimal design results show that in the condition of maintaining feasibility robustness, the proposed approach can obtain a robust solution which the designer is satisfied with the value of objective function and its variation.

  12. Boolean networks with robust and reliable trajectories

    Energy Technology Data Exchange (ETDEWEB)

    Schmal, Christoph; Peixoto, Tiago P; Drossel, Barbara, E-mail: schmal@physik.uni-bielefeld.d, E-mail: tiago@fkp.tu-darmstadt.d, E-mail: drossel@fkp.tu-darmstadt.d [Institut fuer Festkoerperphysik, TU Darmstadt, Hochschulstrasse 6, 64289 Darmstadt (Germany)

    2010-11-15

    We construct and investigate Boolean networks that follow a given reliable trajectory in state space, which is insensitive to fluctuations in the updating schedule and which is also robust against noise. Robustness is quantified as the probability that the dynamics return to the reliable trajectory after a perturbation of the state of a single node. In order to achieve high robustness, we navigate through the space of possible update functions by using an evolutionary algorithm. We constrain the networks to those having the minimum number of connections required to obtain the reliable trajectory. Surprisingly, we find that robustness always reaches values close to 100% during the evolutionary optimization process. The set of update functions can be evolved such that it differs only slightly from that of networks that were not optimized with respect to robustness. The state space of the optimized networks is dominated by the basin of attraction of the reliable trajectory.

  13. A Survey on Robustness in Railway Planning

    DEFF Research Database (Denmark)

    Lusby, Richard Martin; Larsen, Jesper; Bull, Simon Henry

    2017-01-01

    Planning problems in passenger railway range from long term strategic decision making to the detailed planning of operations.Operations research methods have played an increasing role in this planning process. However, recently more attention has been given to considerations of robustness...... in the quality of solutions to individual planning problems, and of operations in general. Robustness in general is the capacity for some system to absorb or resist changes. In the context of railway robustness it is often taken to be the capacity for operations to continue at some level when faced...... with a disruption such as delay or failure. This has resulted in more attention given to the inclusion of robustness measures and objectives in individual planning problems, and to the providing of tools to ensure operations continue under disrupted situations. In this paper we survey the literature on robustness...

  14. International Conference on Robust Statistics 2015

    CERN Document Server

    Basu, Ayanendranath; Filzmoser, Peter; Mukherjee, Diganta

    2016-01-01

    This book offers a collection of recent contributions and emerging ideas in the areas of robust statistics presented at the International Conference on Robust Statistics 2015 (ICORS 2015) held in Kolkata during 12–16 January, 2015. The book explores the applicability of robust methods in other non-traditional areas which includes the use of new techniques such as skew and mixture of skew distributions, scaled Bregman divergences, and multilevel functional data methods; application areas being circular data models and prediction of mortality and life expectancy. The contributions are of both theoretical as well as applied in nature. Robust statistics is a relatively young branch of statistical sciences that is rapidly emerging as the bedrock of statistical analysis in the 21st century due to its flexible nature and wide scope. Robust statistics supports the application of parametric and other inference techniques over a broader domain than the strictly interpreted model scenarios employed in classical statis...

  15. Environmental change makes robust ecological networks fragile

    Science.gov (United States)

    Strona, Giovanni; Lafferty, Kevin D.

    2016-01-01

    Complex ecological networks appear robust to primary extinctions, possibly due to consumers’ tendency to specialize on dependable (available and persistent) resources. However, modifications to the conditions under which the network has evolved might alter resource dependability. Here, we ask whether adaptation to historical conditions can increase community robustness, and whether such robustness can protect communities from collapse when conditions change. Using artificial life simulations, we first evolved digital consumer-resource networks that we subsequently subjected to rapid environmental change. We then investigated how empirical host–parasite networks would respond to historical, random and expected extinction sequences. In both the cases, networks were far more robust to historical conditions than new ones, suggesting that new environmental challenges, as expected under global change, might collapse otherwise robust natural ecosystems.

  16. Employee-driven innovation

    DEFF Research Database (Denmark)

    Kesting, Peter; Ulhøi, John Parm

    2015-01-01

    Purpose – The purpose of this paper is to outline the “grand structure” of the phenomenon in order to identify both the underlying processes and core drivers of employee-driven innovation (EDI). Design/methodology/approach – This is a conceptual paper. It particularly applies the insights...... of contemporary research on routine and organizational decision making to the specific case of EDI. Findings – The main result of the paper is that, from a theoretical point of view, it makes perfect sense to involve ordinary employees in innovation decisions. However, it is also outlined that naıve or ungoverned...... participation is counterproductive, and that it is quite difficult to realize the hidden potential in a supportive way. Research limitations/implications – The main implication is that basic mechanisms for employee participation also apply to innovation decisions, although often in a different way. However...

  17. Consistent model driven architecture

    Science.gov (United States)

    Niepostyn, Stanisław J.

    2015-09-01

    The goal of the MDA is to produce software systems from abstract models in a way where human interaction is restricted to a minimum. These abstract models are based on the UML language. However, the semantics of UML models is defined in a natural language. Subsequently the verification of consistency of these diagrams is needed in order to identify errors in requirements at the early stage of the development process. The verification of consistency is difficult due to a semi-formal nature of UML diagrams. We propose automatic verification of consistency of the series of UML diagrams originating from abstract models implemented with our consistency rules. This Consistent Model Driven Architecture approach enables us to generate automatically complete workflow applications from consistent and complete models developed from abstract models (e.g. Business Context Diagram). Therefore, our method can be used to check practicability (feasibility) of software architecture models.

  18. Muscle-driven nanogenerators

    Science.gov (United States)

    Wang, Zhong L [Marietta, GA; Yang, Rusen [Atlanta, GA

    2011-03-01

    In a method of generating electricity, a plurality of living cells are grown on an array of piezoelectric nanowires so that the cells engage the piezoelectric nanowires. Induced static potentials are extracted from at least one of the piezoelectric nanowires when at least one of the cells deforms the at least one of the piezoelectric nanowires. A cell-driven electrical generator that includes a substrate and a plurality of spaced-apart piezoelectric nanowires disposed on the substrate. A plurality of spaced-apart conductive electrodes interact with the plurality of piezoelectric nanowires. A biological buffer layer that is configured to promote growth of cells is disposed on the substrate so that cells placed on the substrate will grow and engage the piezoelectric nanowires.

  19. Soliton driven angiogenesis

    Science.gov (United States)

    Bonilla, L. L.; Carretero, M.; Terragni, F.; Birnir, B.

    2016-08-01

    Angiogenesis is a multiscale process by which blood vessels grow from existing ones and carry oxygen to distant organs. Angiogenesis is essential for normal organ growth and wounded tissue repair but it may also be induced by tumours to amplify their own growth. Mathematical and computational models contribute to understanding angiogenesis and developing anti-angiogenic drugs, but most work only involves numerical simulations and analysis has lagged. A recent stochastic model of tumour-induced angiogenesis including blood vessel branching, elongation, and anastomosis captures some of its intrinsic multiscale structures, yet allows one to extract a deterministic integropartial differential description of the vessel tip density. Here we find that the latter advances chemotactically towards the tumour driven by a soliton (similar to the famous Korteweg-de Vries soliton) whose shape and velocity change slowly. Analysing these collective coordinates paves the way for controlling angiogenesis through the soliton, the engine that drives this process.

  20. Muscle-driven nanogenerators

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhong L. (Marietta, GA); Yang, Rusen (Atlanta, GA)

    2011-03-01

    In a method of generating electricity, a plurality of living cells are grown on an array of piezoelectric nanowires so that the cells engage the piezoelectric nanowires. Induced static potentials are extracted from at least one of the piezoelectric nanowires when at least one of the cells deforms the at least one of the piezoelectric nanowires. A cell-driven electrical generator that includes a substrate and a plurality of spaced-apart piezoelectric nanowires disposed on the substrate. A plurality of spaced-apart conductive electrodes interact with the plurality of piezoelectric nanowires. A biological buffer layer that is configured to promote growth of cells is disposed on the substrate so that cells placed on the substrate will grow and engage the piezoelectric nanowires.

  1. A Robust Design Method in Product Quality Applications

    Institute of Scientific and Technical Information of China (English)

    ZHANG Shi-an

    2003-01-01

    In order to express information on the quality grade of product designed, the target value of product quality design was described with a fuzzy number in this paper. An alternative to Taguchi′s, the robustness application design method has been recently presented. However, neither Taguchi′s method nor the alternative method is capable of dealing satisfactorily with the frequently encountered situations in which all the noise variables cannot be studied simultaneously. Based on the ideas from response surface modeling, linear models theory, and random effects models, we provide a method for estimation in the robustness application design method in product quality applications. With this new method used, the high-quality ratio of the product designed could be increased, and the ability to resist the influence of various disturbing factors and noise factors could be enhanced.

  2. The Influence of Canalization on the Robustness of Boolean Networks

    CERN Document Server

    Kadelka, Claus; Laubenbacher, Reinhard

    2016-01-01

    Time- and state-discrete dynamical systems are frequently used to model molecular networks. This paper provides a collection of mathematical and computational tools for the study of robustness in Boolean network models. The focus is on networks governed by $k$-canalizing functions, a recently introduced class of Boolean functions that contains the well-studied class of nested canalizing functions. The activities and sensitivity of a function quantify the impact of input changes on the function output. This paper generalizes the latter concept to $c$-sensitivity and provides formulas for the activities and $c$-sensitivity of general $k$-canalizing functions as well as canalizing functions with more precisely defined structure. A popular measure for the robustness of a network, the Derrida value, can be expressed as a weighted sum of the $c$-sensitivities of the governing canalizing functions, and can also be calculated for a stochastic extension of Boolean networks. These findings provide a computationally eff...

  3. Robust facial landmark detection based on initializing multiple poses

    Directory of Open Access Journals (Sweden)

    Xin Chai

    2016-10-01

    Full Text Available For robot systems, robust facial landmark detection is the first and critical step for face-based human identification and facial expression recognition. In recent years, the cascaded-regression-based method has achieved excellent performance in facial landmark detection. Nevertheless, it still has certain weakness, such as high sensitivity to the initialization. To address this problem, regression based on multiple initializations is established in a unified model; face shapes are then estimated independently according to these initializations. With a ranking strategy, the best estimate is selected as the final output. Moreover, a face shape model based on restricted Boltzmann machines is built as a constraint to improve the robustness of ranking. Experiments on three challenging datasets demonstrate the effectiveness of the proposed facial landmark detection method against state-of-the-art methods.

  4. Robust graph coloring based on the matrix semi-tensor product with application to examination timetabling

    Institute of Scientific and Technical Information of China (English)

    Meirong XU; Yuzhen WANG; Airong WEI

    2014-01-01

    This paper investigates the robust graph coloring problem with application to a kind of examination timetabling by using the matrix semi-tensor product, and presents a number of new results and algorithms. First, using the matrix semi-tensor product, the robust graph coloring is expressed into a kind of optimization problem taking in an algebraic form of matrices, based on which an algorithm is designed to find all the most robust coloring schemes for any simple graph. Second, an equivalent problem of robust graph coloring is studied, and a necessary and sufficient condition is proposed, from which a new algorithm to find all the most robust coloring schemes is established. Third, a kind of examination timetabling is discussed by using the obtained results, and a method to design a practicable timetabling scheme is presented. Finally, the effectiveness of the results/algorithms presented in this paper is shown by two illustrative examples.

  5. A Comparative Study of Kernel and Robust Canonical Correlation Analysis

    Directory of Open Access Journals (Sweden)

    Ashad M. Alam

    2010-02-01

    Full Text Available A number of measures of canonical correlation coefficient are now used in multimedia related fields like object recognition, image segmentation facial expression recognition and pattern recognition in the different literature. Some robust forms of classical canonical correlation coefficient are introduced recently to address the robustness issue of the canonical coefficient in the presence of outliers and departure from normality. Also a few number of kernels are used in canonical analysis to capture nonlinear relationship in data space, which is linear in some higher dimensional feature space. But not much work has been done to investigate their relative performances through i simulation from the view point of sensitivity, breakdown analysis as well as ii using real data sets. In this paper an attempt has been made to compare performances of kernel canonical correlation coefficients (Gaussian function, Laplacian function and Polynomial function with that of robust and classical canonical correlation coefficient measures using simulation with five sample sizes (50, 500, 1000, 1500 and 2000, influence function, breakdown point along with several real data and a multi-modal data sets, focusing on the specific case of segmented images with associated text. We investigate the bias, mean square error(MISE, qualitative robustness index (RI, sensitivity curve of each estimator under a variety of situations and also employ box plots and scatter plots of canonical variates to judge their performances. We have observed that the class of kernel estimators perform better than the class of classical and robust estimators in general and the kernel estimator with Laplacian function has shown the best performance for large sample size and break down is high in case of nonlinear data.

  6. Deriving robust and globalized robust solutions of uncertain linear programs having general convex uncertainty sets

    NARCIS (Netherlands)

    Gorissen, B.L.; Blanc, J.P.C.; den Hertog, D.; Ben-Tal, A.

    We propose a new way to derive tractable robust counterparts of a linear program based on the duality between the robust (“pessimistic”) primal problem and its “optimistic” dual. First we obtain a new convex reformulation of the dual problem of a robust linear program, and then show how to construct

  7. System-driven and oscillator-dependent circadian transcription in mice with a conditionally active liver clock.

    Directory of Open Access Journals (Sweden)

    Benoît Kornmann

    2007-02-01

    Full Text Available The mammalian circadian timing system consists of a master pacemaker in neurons of the suprachiasmatic nucleus (SCN and clocks of a similar molecular makeup in most peripheral body cells. Peripheral oscillators are self-sustained and cell autonomous, but they have to be synchronized by the SCN to ensure phase coherence within the organism. In principle, the rhythmic expression of genes in peripheral organs could thus be driven not only by local oscillators, but also by circadian systemic signals. To discriminate between these mechanisms, we engineered a mouse strain with a conditionally active liver clock, in which REV-ERBalpha represses the transcription of the essential core clock gene Bmal1 in a doxycycline-dependent manner. We examined circadian liver gene expression genome-wide in mice in which hepatocyte oscillators were either running or arrested, and found that the rhythmic transcription of most genes depended on functional hepatocyte clocks. However, we discovered 31 genes, including the core clock gene mPer2, whose expression oscillated robustly irrespective of whether the liver clock was running or not. By contrast, in liver explants cultured in vitro, circadian cycles of mPer2::luciferase bioluminescence could only be observed when hepatocyte oscillators were operational. Hence, the circadian cycles observed in the liver of intact animals without functional hepatocyte oscillators were likely generated by systemic signals. The finding that rhythmic mPer2 expression can be driven by both systemic cues and local oscillators suggests a plausible mechanism for the phase entrainment of subsidiary clocks in peripheral organs.

  8. H∞ robust fault-tolerant controller design for an autonomous underwater vehicle's navigation control system

    Science.gov (United States)

    Cheng, Xiang-Qin; Qu, Jing-Yuan; Yan, Zhe-Ping; Bian, Xin-Qian

    2010-03-01

    In order to improve the security and reliability for autonomous underwater vehicle (AUV) navigation, an H∞ robust fault-tolerant controller was designed after analyzing variations in state-feedback gain. Operating conditions and the design method were then analyzed so that the control problem could be expressed as a mathematical optimization problem. This permitted the use of linear matrix inequalities (LMI) to solve for the H∞ controller for the system. When considering different actuator failures, these conditions were then also mathematically expressed, allowing the H∞ robust controller to solve for these events and thus be fault-tolerant. Finally, simulation results showed that the H∞ robust fault-tolerant controller could provide precise AUV navigation control with strong robustness.

  9. The evolution of robust development and homeostasis in artificial organisms.

    Directory of Open Access Journals (Sweden)

    David Basanta

    2008-03-01

    Full Text Available During embryogenesis, multicellular animals are shaped via cell proliferation, cell rearrangement, and apoptosis. At the end of development, tissue architecture is then maintained through balanced rates of cell proliferation and loss. Here, we take an in silico approach to look for generic systems features of morphogenesis in multicellular animals that arise as a consequence of the evolution of development. Using artificial evolution, we evolved cellular automata-based digital organisms that have distinct embryonic and homeostatic phases of development. Although these evolved organisms use a variety of strategies to maintain their form over time, organisms of different types were all found to rapidly recover from environmental damage in the form of wounds. This regenerative response was most robust in an organism with a stratified tissue-like architecture. An evolutionary analysis revealed that evolution itself contributed to the ability of this organism to maintain its form in the face of genetic and environmental perturbation, confirming the results of previous studies. In addition, the exceptional robustness of this organism to surface injury was found to result from an upward flux of cells, driven in part by cell divisions with a stable niche at the tissue base. Given the general nature of the model, our results lead us to suggest that many of the robust systems properties observed in real organisms, including scar-free wound-healing in well-protected embryos and the layered tissue architecture of regenerating epithelial tissues, may be by-products of the evolution of morphogenesis, rather than the direct result of selection.

  10. Periodic expression of Kv10.1 driven by pRb/E2F1 contributes to G2/M progression of cancer and non-transformed cells.

    Science.gov (United States)

    Urrego, Diana; Movsisyan, Naira; Ufartes, Roser; Pardo, Luis A

    2016-01-01

    Progression of cell cycle is associated with changes in K(+) channel expression and activity. In this study, we report that Kv10.1, a K(+) channel that increases cell proliferation and tumor growth, is regulated at the transcriptional level by the pRb/E2F1 pathway. De-repression of E2F1 by HPV-E7 oncoprotein leads to increased expression of Kv10.1. In proliferating cells, E2F1 transcription factor binds directly to the Kv10.1 promoter during (or close to) G2/M, resulting in transient expression of the channel. Importantly, this happens not only in cancer cells but also in non-transformed cells. Lack of Kv10.1 in both cancer and non-transformed cells resulted in prolonged G2/M phase, as indicated by phosphorylation of Cdk1 (Y15) and sustained pRb hyperphosphorylation. Our results strongly suggest that Kv10.1 expression is coupled to cell cycle progression and facilitates G2/M progression in both healthy and tumor cells.

  11. Robust Multiobjective Controllability of Complex Neuronal Networks.

    Science.gov (United States)

    Tang, Yang; Gao, Huijun; Du, Wei; Lu, Jianquan; Vasilakos, Athanasios V; Kurths, Jurgen

    2016-01-01

    This paper addresses robust multiobjective identification of driver nodes in the neuronal network of a cat's brain, in which uncertainties in determination of driver nodes and control gains are considered. A framework for robust multiobjective controllability is proposed by introducing interval uncertainties and optimization algorithms. By appropriate definitions of robust multiobjective controllability, a robust nondominated sorting adaptive differential evolution (NSJaDE) is presented by means of the nondominated sorting mechanism and the adaptive differential evolution (JaDE). The simulation experimental results illustrate the satisfactory performance of NSJaDE for robust multiobjective controllability, in comparison with six statistical methods and two multiobjective evolutionary algorithms (MOEAs): nondominated sorting genetic algorithms II (NSGA-II) and nondominated sorting composite differential evolution. It is revealed that the existence of uncertainties in choosing driver nodes and designing control gains heavily affects the controllability of neuronal networks. We also unveil that driver nodes play a more drastic role than control gains in robust controllability. The developed NSJaDE and obtained results will shed light on the understanding of robustness in controlling realistic complex networks such as transportation networks, power grid networks, biological networks, etc.

  12. Biological Robustness: Paradigms, Mechanisms, and Systems Principles

    Directory of Open Access Journals (Sweden)

    James Michael Whitacre

    2012-05-01

    Full Text Available Robustness has been studied through the analysis of data sets, simulations, and a variety of experimental techniques that each have their own limitations but together confirm the ubiquity of biological robustness. Recent trends suggest that different types of perturbation (e.g. mutational, environmental are commonly stabilized by similar mechanisms, and system sensitivities often display a long-tailed distribution with relatively few perturbations representing the majority of sensitivities. Conceptual paradigms from network theory, control theory, complexity science, and natural selection have been used to understand robustness, however each paradigm has a limited scope of applicability and there has been little discussion of the conditions that determine this scope or the relationships between paradigms. Systems properties such as modularity, bow-tie architectures, degeneracy, and other topological features are often positively associated with robust traits, however common underlying mechanisms are rarely mentioned. For instance, many system properties support robustness through functional redundancy or through response diversity with responses regulated by competitive exclusion and cooperative facilitation. Moreover, few studies compare and contrast alternative strategies for achieving robustness such as homeostasis, adaptive plasticity, environment shaping, and environment tracking. These strategies share similarities in their utilization of adaptive and self-organization processes that are not well appreciated yet might be suggestive of reusable building blocks for generating robust behavior.

  13. Multi-objective robust controller synthesis for discrete-time systems with convex polytopic uncertain domain

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yan-hu; YAN Wen-jun; LU Jian-ning; ZHAO Guang-zhou

    2005-01-01

    Multi-objective robust state-feedback controller synthesis problems for linear discrete-time uncertain systems are addressed. Based on parameter-dependent Lyapunov functions, the Gl2 and GH2 norm expressed in terms of LMI (Linear Matrix Inequality) characterizations are further generalized to cope with the robust analysis for convex polytopic uncertain system.Robust state-feedback controller synthesis conditions are also derived for this class of uncertain systems. Using the above results,multi-objective state-feedback controller synthesis procedures which involve the LMI optimization technique are developed and less conservative than the existing one. An illustrative example verified the validity of the approach.

  14. Danish Requirements for Robustness of Structures

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Christensen, H. H.

    2006-01-01

    Increased use of advanced types of structures with limited redundancy and serious failure consequences combined with strengthened requirements to efficiency in design and execution as well as increased risk of human errors necessitates requirements for the robustness of new structures, essential....... This paper describes the background of the revised robustness requirements implemented in the Danish Code of Practice for Safety of Structures in 2003 [1, 2, 3]. According to the Danish design rules robustness shall be documented for all structures where consequences of failure are serious. This paper...

  15. Modeling and robust control of wind turbine

    Science.gov (United States)

    Gilev, Bogdan

    2016-12-01

    In this paper a model of a wind turbine is evaluated, consisting of: wind speed model, mechanical and electrical model of generator and tower oscillation model. This model is linearized around of a nominal point. By using the linear model with uncertainties is synthesized a uncertain model. By using the uncertain model and robust control theory is developed a robust controller, which provide mode of stabilizing the rotor frequency and damping the tower oscillations. Finally is simulated work of nonlinear system and robust controller

  16. Robust Spectral Estimation of Track Irregularity

    Institute of Scientific and Technical Information of China (English)

    Fu Wenjuan; Chen Chunjun

    2005-01-01

    Because the existing spectral estimation methods for railway track irregularity analysis are very sensitive to outliers, a robust spectral estimation method is presented to process track irregularity signals. The proposed robust method is verified using 100 groups of clean/contaminated data reflecting he vertical profile irregularity taken from Bejing-Guangzhou railway with a sampling frequency of 33 data every 10 m, and compared with the Auto Regressive (AR) model. The experimental results show that the proposed robust estimation is resistible to noise and insensitive to outliers, and is superior to the AR model in terms of efficiency, stability and reliability.

  17. Design Robust Controller for Rotary Kiln

    Directory of Open Access Journals (Sweden)

    Omar D. Hernández-Arboleda

    2013-11-01

    Full Text Available This paper presents the design of a robust controller for a rotary kiln. The designed controller is a combination of a fractional PID and linear quadratic regulator (LQR, these are not used to control the kiln until now, in addition robustness criteria are evaluated (gain margin, phase margin, strength gain, rejecting high frequency noise and sensitivity applied to the entire model (controller-plant, obtaining good results with a frequency range of 0.020 to 90 rad/s, which contributes to the robustness of the system.

  18. Network robustness under large-scale attacks

    CERN Document Server

    Zhou, Qing; Liu, Ruifang; Cui, Shuguang

    2014-01-01

    Network Robustness under Large-Scale Attacks provides the analysis of network robustness under attacks, with a focus on large-scale correlated physical attacks. The book begins with a thorough overview of the latest research and techniques to analyze the network responses to different types of attacks over various network topologies and connection models. It then introduces a new large-scale physical attack model coined as area attack, under which a new network robustness measure is introduced and applied to study the network responses. With this book, readers will learn the necessary tools to evaluate how a complex network responds to random and possibly correlated attacks.

  19. Robust control of an aircraft model

    Energy Technology Data Exchange (ETDEWEB)

    Werner, H. [Bochum Univ. (Germany). Fakultaet fuer Elektrotechnik

    1999-12-01

    A new multimodel approach to robust controller design is illustrated by a practical application: for a laboratory aircraft model, a robust controller is designed simultaneously for normal operating conditions and for propeller failure. Based on a linear model for each operating mode, an LMI formulation of the problem and convex programming are used to search for a state feedback controller which achieves the objective. This state feedback design is then realized simultaneously in both operating modes by a controller which is based on fast output sampling. Robust performance is demonstrated by experimental results. (orig.)

  20. Robust control of an aircraft model

    Energy Technology Data Exchange (ETDEWEB)

    Werner, H. (Bochum Univ. (Germany). Fakultaet fuer Elektrotechnik)

    1999-01-01

    A new multimodel approach to robust controller design is illustrated by a practical application: for a laboratory aircraft model, a robust controller is designed simultaneously for normal operating conditions and for propeller failure. Based on a linear model for each operating mode, an LMI formulation of the problem and convex programming are used to search for a state feedback controller which achieves the objective. This state feedback design is then realized simultaneously in both operating modes by a controller which is based on fast output sampling. Robust performance is demonstrated by experimental results. (orig.)