Sample records for pathways redundantly control

  1. Redundancy control in pathway databases (ReCiPa): an application for improving gene-set enrichment analysis in Omics studies and "Big data" biology.

    PubMed

    Vivar, Juan C; Pemu, Priscilla; McPherson, Ruth; Ghosh, Sujoy

    2013-08-01

    Abstract Unparalleled technological advances have fueled an explosive growth in the scope and scale of biological data and have propelled life sciences into the realm of "Big Data" that cannot be managed or analyzed by conventional approaches. Big Data in the life sciences are driven primarily via a diverse collection of 'omics'-based technologies, including genomics, proteomics, metabolomics, transcriptomics, metagenomics, and lipidomics. Gene-set enrichment analysis is a powerful approach for interrogating large 'omics' datasets, leading to the identification of biological mechanisms associated with observed outcomes. While several factors influence the results from such analysis, the impact from the contents of pathway databases is often under-appreciated. Pathway databases often contain variously named pathways that overlap with one another to varying degrees. Ignoring such redundancies during pathway analysis can lead to the designation of several pathways as being significant due to high content-similarity, rather than truly independent biological mechanisms. Statistically, such dependencies also result in correlated p values and overdispersion, leading to biased results. We investigated the level of redundancies in multiple pathway databases and observed large discrepancies in the nature and extent of pathway overlap. This prompted us to develop the application, ReCiPa (Redundancy Control in Pathway Databases), to control redundancies in pathway databases based on user-defined thresholds. Analysis of genomic and genetic datasets, using ReCiPa-generated overlap-controlled versions of KEGG and Reactome pathways, led to a reduction in redundancy among the top-scoring gene-sets and allowed for the inclusion of additional gene-sets representing possibly novel biological mechanisms. Using obesity as an example, bioinformatic analysis further demonstrated that gene-sets identified from overlap-controlled pathway databases show stronger evidence of prior association to obesity compared to pathways identified from the original databases.

  2. Computational modeling of the EGFR network elucidates control mechanisms regulating signal dynamics

    PubMed Central

    2009-01-01

    Background The epidermal growth factor receptor (EGFR) signaling pathway plays a key role in regulation of cellular growth and development. While highly studied, it is still not fully understood how the signal is orchestrated. One of the reasons for the complexity of this pathway is the extensive network of inter-connected components involved in the signaling. In the aim of identifying critical mechanisms controlling signal transduction we have performed extensive analysis of an executable model of the EGFR pathway using the stochastic pi-calculus as a modeling language. Results Our analysis, done through simulation of various perturbations, suggests that the EGFR pathway contains regions of functional redundancy in the upstream parts; in the event of low EGF stimulus or partial system failure, this redundancy helps to maintain functional robustness. Downstream parts, like the parts controlling Ras and ERK, have fewer redundancies, and more than 50% inhibition of specific reactions in those parts greatly attenuates signal response. In addition, we suggest an abstract model that captures the main control mechanisms in the pathway. Simulation of this abstract model suggests that without redundancies in the upstream modules, signal transduction through the entire pathway could be attenuated. In terms of specific control mechanisms, we have identified positive feedback loops whose role is to prolong the active state of key components (e.g., MEK-PP, Ras-GTP), and negative feedback loops that help promote signal adaptation and stabilization. Conclusions The insights gained from simulating this executable model facilitate the formulation of specific hypotheses regarding the control mechanisms of the EGFR signaling, and further substantiate the benefit to construct abstract executable models of large complex biological networks. PMID:20028552

  3. Functional redundancy in the control of seedling growth by the karrikin signaling pathway.

    PubMed

    Stanga, John P; Morffy, Nicholas; Nelson, David C

    2016-06-01

    SMAX1 and SMXL2 control seedling growth, demonstrating functional redundancy within a gene family that mediates karrikin and strigolactone responses. Strigolactones (SLs) are plant hormones with butenolide moieties that control diverse aspects of plant growth, including shoot branching. Karrikins (KARs) are butenolide molecules found in smoke that enhance seed germination and seedling photomorphogenesis. In Arabidopsis thaliana, SLs and KARs signal through the α/β hydrolases D14 and KAI2, respectively. The F-box protein MAX2 is essential for both signaling pathways. SUPPRESSOR OF MAX2 1 (SMAX1) plays a prominent role in KAR-regulated growth downstream of MAX2, and SMAX1-LIKE genes SMXL6, SMXL7, and SMXL8 mediate SL responses. We previously found that smax1 loss-of-function mutants display constitutive KAR response phenotypes, including reduced seed dormancy and hypersensitive growth responses to light in seedlings. However, smax1 seedlings remain slightly responsive to KARs, suggesting that there is functional redundancy in karrikin signaling. SMXL2 is a strong candidate for this redundancy because it is the closest paralog of SMAX1, and because its expression is regulated by KAR signaling. Here, we present evidence that SMXL2 controls hypocotyl growth and expression of the KAR/SL transcriptional markers KUF1, IAA1, and DLK2 redundantly with SMAX1. Hypocotyl growth in the smax1 smxl2 double mutant is insensitive to KAR and SL, and etiolated smax1 smxl2 seedlings have reduced hypocotyl elongation. However, smxl2 has little or no effect on seed germination, leaf shape, or petiole orientation, which appear to be predominantly controlled by SMAX1. Neither SMAX1 nor SMXL2 affect axillary branching or inflorescence height, traits that are under SL control. These data support the model that karrikin and strigolactone responses are mediated by distinct subclades of the SMXL family, and further the case for parallel butenolide signaling pathways that evolved through ancient KAI2 and SMXL duplications.

  4. Interactions of UNC-34 Enabled With Rac GTPases and the NIK Kinase MIG-15 in Caenorhabditis elegans Axon Pathfinding and Neuronal Migration

    PubMed Central

    Shakir, M. Afaq; Gill, Jason S.; Lundquist, Erik A.

    2006-01-01

    Many genes that affect axon pathfinding and cell migration have been identified. Mechanisms by which these genes and the molecules they encode interact with one another in pathways and networks to control developmental events are unclear. Rac GTPases, the cytoskeletal signaling molecule Enabled, and NIK kinase have all been implicated in regulating axon pathfinding and cell migration. Here we present evidence that, in Caenorhabditis elegans, three Rac GTPases, CED-10, RAC-2, and MIG-2, define three redundant pathways that each control axon pathfinding, and that the NIK kinase MIG-15 acts in each Rac pathway. Furthermore, we show that the Enabled molecule UNC-34 defines a fourth partially redundant pathway that acts in parallel to Rac/MIG-15 signaling in axon pathfinding. Enabled and the three Racs also act redundantly to mediate AQR and PQR neuronal cell migration. The Racs and UNC-34 Ena might all control the formation of actin-based protrusive structures (lamellipodia and filopodia) that mediate growth cone outgrowth and cell migration. MIG-15 does not act with the three Racs in execution of cell migration. Rather, MIG-15 affects direction of PQR neuronal migration, similar to UNC-40 and DPY-19, which control initial Q cell polarity, and Wnt signaling, which acts later to control Q cell-directed migration. MIG-2 Rac, which acts with CED-10 Rac, RAC-2 Rac, and UNC-34 Ena in axon pathfinding and cell migration, also acts with MIG-15 in PQR directional migration. PMID:16204220

  5. Drosophila Activin- and the Activin-like product Dawdle function redundantly to regulate proliferation in the larval brain.

    PubMed

    Zhu, Changqi C; Boone, Jason Q; Jensen, Philip A; Hanna, Scott; Podemski, Lynn; Locke, John; Doe, Chris Q; O'Connor, Michael B

    2008-02-01

    The Drosophila Activin-like ligands Activin-beta and Dawdle control several aspects of neuronal morphogenesis, including mushroom body remodeling, dorsal neuron morphogenesis and motoneuron axon guidance. Here we show that the same two ligands act redundantly through the Activin receptor Babo and its transcriptional mediator Smad2 (Smox), to regulate neuroblast numbers and proliferation rates in the developing larval brain. Blocking this pathway results in the development of larvae with small brains and aberrant photoreceptor axon targeting, and restoring babo function in neuroblasts rescued these mutant phenotypes. These results suggest that the Activin signaling pathway is required for producing the proper number of neurons to enable normal connection of incoming photoreceptor axons to their targets. Furthermore, as the Activin pathway plays a key role in regulating propagation of mouse and human embryonic stem cells, our observation that it also regulates neuroblast numbers and proliferation in Drosophila suggests that involvement of Activins in controlling stem cell propagation may be a common regulatory feature of this family of TGF-beta-type ligands.

  6. Morphological properties of vestibulospinal neurons in primates

    NASA Technical Reports Server (NTRS)

    Boyle, Richard; Johanson, Curt

    2003-01-01

    The lateral and medial vestibulospinal tracts constitute the major descending pathways controlling extensor musculature of the body. We examined the axon morphology and synaptic input patterns and targets in the cervical spinal segments from these tract cells using intracellular recording and biocytin labeling in the squirrel monkey. Lumbosacral projecting cells represent a private, and mostly rapid, communication pathway between the dorsal Deiters' nucleus and the motor circuits controlling the lower limbs and tail. The cervical projecting cells provide both redundant and variable synaptic input to spinal cell groups, suggesting both general and specific control of the head and neck reflexes.

  7. A system-level mathematical model of Basal Ganglia motor-circuit for kinematic planning of arm movements.

    PubMed

    Salimi-Badr, Armin; Ebadzadeh, Mohammad Mehdi; Darlot, Christian

    2018-01-01

    In this paper, a novel system-level mathematical model of the Basal Ganglia (BG) for kinematic planning, is proposed. An arm composed of several segments presents a geometric redundancy. Thus, selecting one trajectory among an infinite number of possible ones requires overcoming redundancy, according to some kinds of optimization. Solving this optimization is assumed to be the function of BG in planning. In the proposed model, first, a mathematical solution of kinematic planning is proposed for movements of a redundant arm in a plane, based on minimizing energy consumption. Next, the function of each part in the model is interpreted as a possible role of a nucleus of BG. Since the kinematic variables are considered as vectors, the proposed model is presented based on the vector calculus. This vector model predicts different neuronal populations in BG which is in accordance with some recent experimental studies. According to the proposed model, the function of the direct pathway is to calculate the necessary rotation of each joint, and the function of the indirect pathway is to control each joint rotation considering the movement of the other joints. In the proposed model, the local feedback loop between Subthalamic Nucleus and Globus Pallidus externus is interpreted as a local memory to store the previous amounts of movements of the other joints, which are utilized by the indirect pathway. In this model, activities of dopaminergic neurons would encode, at short-term, the error between the desired and actual positions of the end-effector. The short-term modulating effect of dopamine on Striatum is also modeled as cross product. The model is simulated to generate the commands of a redundant manipulator. The performance of the model is studied for different reaching movements between 8 points in a plane. Finally, some symptoms of Parkinson's disease such as bradykinesia and akinesia are simulated by modifying the model parameters, inspired by the dopamine depletion. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Genetic and Genomic Insights into the Role of Benzoate-Catabolic Pathway Redundancy in Burkholderia xenovorans LB400†

    PubMed Central

    Denef, V. J.; Klappenbach, J. A.; Patrauchan, M. A.; Florizone, C.; Rodrigues, J. L. M.; Tsoi, T. V.; Verstraete, W.; Eltis, L. D.; Tiedje, J. M.

    2006-01-01

    Transcriptomic and proteomic analyses of Burkholderia xenovorans LB400, a potent polychlorinated biphenyl (PCB) degrader, have implicated growth substrate- and phase-dependent expression of three benzoate-catabolizing pathways: a catechol ortho cleavage (ben-cat) pathway and two benzoyl-coenzyme A pathways, encoded by gene clusters on the large chromosome (boxC) and the megaplasmid (boxM). To elucidate the significance of this apparent redundancy, we constructed mutants with deletions of the ben-cat pathway (the ΔbenABCD::kan mutant), the boxC pathway (the ΔboxABC::kan mutant), and both pathways (the ΔbenABCDΔ boxABC::kan mutant). All three mutants oxidized benzoate in resting-cell assays. However, the ΔbenABCD::kan and ΔbenABCD ΔboxABC::kan mutants grew at reduced rates on benzoate and displayed increased lag phases. By contrast, growth on succinate, on 4-hydroxybenzoate, and on biphenyl was unaffected. Microarray and proteomic analyses revealed that cells of the ΔbenABCD::kan mutant growing on benzoate expressed both box pathways. Overall, these results indicate that all three pathways catabolize benzoate. Deletion of benABCD abolished the ability of LB400 to grow using 3-chlorobenzoate. None of the benzoate pathways could degrade 2- or 4-chlorobenzoate, indicating that the pathway redundancy does not directly contribute to LB400's PCB-degrading capacities. Finally, an extensive sigmaE-regulated oxidative stress response not present in wild-type LB400 grown on benzoate was detected in these deletion mutants, supporting our earlier suggestion that the box pathways are preferentially active under reduced oxygen tension. Our data further substantiate the expansive network of tightly interconnected and complexly regulated aromatic degradation pathways in LB400. PMID:16391095

  9. Ecological network analysis for a virtual water network.

    PubMed

    Fang, Delin; Chen, Bin

    2015-06-02

    The notions of virtual water flows provide important indicators to manifest the water consumption and allocation between different sectors via product transactions. However, the configuration of virtual water network (VWN) still needs further investigation to identify the water interdependency among different sectors as well as the network efficiency and stability in a socio-economic system. Ecological network analysis is chosen as a useful tool to examine the structure and function of VWN and the interactions among its sectors. A balance analysis of efficiency and redundancy is also conducted to describe the robustness (RVWN) of VWN. Then, network control analysis and network utility analysis are performed to investigate the dominant sectors and pathways for virtual water circulation and the mutual relationships between pairwise sectors. A case study of the Heihe River Basin in China shows that the balance between efficiency and redundancy is situated on the left side of the robustness curve with less efficiency and higher redundancy. The forestation, herding and fishing sectors and industrial sectors are found to be the main controllers. The network tends to be more mutualistic and synergic, though some competitive relationships that weaken the virtual water circulation still exist.

  10. Method and system for redundancy management of distributed and recoverable digital control system

    NASA Technical Reports Server (NTRS)

    Stange, Kent (Inventor); Hess, Richard (Inventor); Kelley, Gerald B (Inventor); Rogers, Randy (Inventor)

    2012-01-01

    A method and system for redundancy management is provided for a distributed and recoverable digital control system. The method uses unique redundancy management techniques to achieve recovery and restoration of redundant elements to full operation in an asynchronous environment. The system includes a first computing unit comprising a pair of redundant computational lanes for generating redundant control commands. One or more internal monitors detect data errors in the control commands, and provide a recovery trigger to the first computing unit. A second redundant computing unit provides the same features as the first computing unit. A first actuator control unit is configured to provide blending and monitoring of the control commands from the first and second computing units, and to provide a recovery trigger to each of the first and second computing units. A second actuator control unit provides the same features as the first actuator control unit.

  11. Murine Dishevelled 3 Functions in Redundant Pathways with Dishevelled 1 and 2 in Normal Cardiac Outflow Tract, Cochlea, and Neural Tube Development

    PubMed Central

    Etheridge, S. Leah; Ray, Saugata; Li, Shuangding; Hamblet, Natasha S.; Lijam, Nardos; Tsang, Michael; Greer, Joy; Kardos, Natalie; Wang, Jianbo; Sussman, Daniel J.; Chen, Ping; Wynshaw-Boris, Anthony

    2008-01-01

    Dishevelled (Dvl) proteins are important signaling components of both the canonical β-catenin/Wnt pathway, which controls cell proliferation and patterning, and the planar cell polarity (PCP) pathway, which coordinates cell polarity within a sheet of cells and also directs convergent extension cell (CE) movements that produce narrowing and elongation of the tissue. Three mammalian Dvl genes have been identified and the developmental roles of Dvl1 and Dvl2 were previously determined. Here, we identify the functions of Dvl3 in development and provide evidence of functional redundancy among the three murine Dvls. Dvl3 −/− mice died perinatally with cardiac outflow tract abnormalities, including double outlet right ventricle and persistent truncus arteriosis. These mutants also displayed a misorientated stereocilia in the organ of Corti, a phenotype that was enhanced with the additional loss of a single allele of the PCP component Vangl2/Ltap (LtapLp/+). Although neurulation appeared normal in both Dvl3 −/− and LtapLp/+ mutants, Dvl3 +/−;LtapLp/+ combined mutants displayed incomplete neural tube closure. Importantly, we show that many of the roles of Dvl3 are also shared by Dvl1 and Dvl2. More severe phenotypes were observed in Dvl3 mutants with the deficiency of another Dvl, and increasing Dvl dosage genetically with Dvl transgenes demonstrated the ability of Dvls to compensate for each other to enable normal development. Interestingly, global canonical Wnt signaling appeared largely unaffected in the double Dvl mutants, suggesting that low Dvl levels are sufficient for functional canonical Wnt signals. In summary, we demonstrate that Dvl3 is required for cardiac outflow tract development and describe its importance in the PCP pathway during neurulation and cochlea development. Finally, we establish several developmental processes in which the three Dvls are functionally redundant. PMID:19008950

  12. Murine dishevelled 3 functions in redundant pathways with dishevelled 1 and 2 in normal cardiac outflow tract, cochlea, and neural tube development.

    PubMed

    Etheridge, S Leah; Ray, Saugata; Li, Shuangding; Hamblet, Natasha S; Lijam, Nardos; Tsang, Michael; Greer, Joy; Kardos, Natalie; Wang, Jianbo; Sussman, Daniel J; Chen, Ping; Wynshaw-Boris, Anthony

    2008-11-01

    Dishevelled (Dvl) proteins are important signaling components of both the canonical beta-catenin/Wnt pathway, which controls cell proliferation and patterning, and the planar cell polarity (PCP) pathway, which coordinates cell polarity within a sheet of cells and also directs convergent extension cell (CE) movements that produce narrowing and elongation of the tissue. Three mammalian Dvl genes have been identified and the developmental roles of Dvl1 and Dvl2 were previously determined. Here, we identify the functions of Dvl3 in development and provide evidence of functional redundancy among the three murine Dvls. Dvl3(-/-) mice died perinatally with cardiac outflow tract abnormalities, including double outlet right ventricle and persistent truncus arteriosis. These mutants also displayed a misorientated stereocilia in the organ of Corti, a phenotype that was enhanced with the additional loss of a single allele of the PCP component Vangl2/Ltap (LtapLp/+). Although neurulation appeared normal in both Dvl3(-/-) and LtapLp/+ mutants, Dvl3(+/-);LtapLp/+ combined mutants displayed incomplete neural tube closure. Importantly, we show that many of the roles of Dvl3 are also shared by Dvl1 and Dvl2. More severe phenotypes were observed in Dvl3 mutants with the deficiency of another Dvl, and increasing Dvl dosage genetically with Dvl transgenes demonstrated the ability of Dvls to compensate for each other to enable normal development. Interestingly, global canonical Wnt signaling appeared largely unaffected in the double Dvl mutants, suggesting that low Dvl levels are sufficient for functional canonical Wnt signals. In summary, we demonstrate that Dvl3 is required for cardiac outflow tract development and describe its importance in the PCP pathway during neurulation and cochlea development. Finally, we establish several developmental processes in which the three Dvls are functionally redundant.

  13. Patterning of leaf vein networks by convergent auxin transport pathways.

    PubMed

    Sawchuk, Megan G; Edgar, Alexander; Scarpella, Enrico

    2013-01-01

    The formation of leaf vein patterns has fascinated biologists for centuries. Transport of the plant signal auxin has long been implicated in vein patterning, but molecular details have remained unclear. Varied evidence suggests a central role for the plasma-membrane (PM)-localized PIN-FORMED1 (PIN1) intercellular auxin transporter of Arabidopsis thaliana in auxin-transport-dependent vein patterning. However, in contrast to the severe vein-pattern defects induced by auxin transport inhibitors, pin1 mutant leaves have only mild vein-pattern defects. These defects have been interpreted as evidence of redundancy between PIN1 and the other four PM-localized PIN proteins in vein patterning, redundancy that underlies many developmental processes. By contrast, we show here that vein patterning in the Arabidopsis leaf is controlled by two distinct and convergent auxin-transport pathways: intercellular auxin transport mediated by PM-localized PIN1 and intracellular auxin transport mediated by the evolutionarily older, endoplasmic-reticulum-localized PIN6, PIN8, and PIN5. PIN6 and PIN8 are expressed, as PIN1 and PIN5, at sites of vein formation. pin6 synthetically enhances pin1 vein-pattern defects, and pin8 quantitatively enhances pin1pin6 vein-pattern defects. Function of PIN6 is necessary, redundantly with that of PIN8, and sufficient to control auxin response levels, PIN1 expression, and vein network formation; and the vein pattern defects induced by ectopic PIN6 expression are mimicked by ectopic PIN8 expression. Finally, vein patterning functions of PIN6 and PIN8 are antagonized by PIN5 function. Our data define a new level of control of vein patterning, one with repercussions on other patterning processes in the plant, and suggest a mechanism to select cell files specialized for vascular function that predates evolution of PM-localized PIN proteins.

  14. Cartesian control of redundant robots

    NASA Technical Reports Server (NTRS)

    Colbaugh, R.; Glass, K.

    1989-01-01

    A Cartesian-space position/force controller is presented for redundant robots. The proposed control structure partitions the control problem into a nonredundant position/force trajectory tracking problem and a redundant mapping problem between Cartesian control input F is a set member of the set R(sup m) and robot actuator torque T is a set member of the set R(sup n) (for redundant robots, m is less than n). The underdetermined nature of the F yields T map is exploited so that the robot redundancy is utilized to improve the dynamic response of the robot. This dynamically optimal F yields T map is implemented locally (in time) so that it is computationally efficient for on-line control; however, it is shown that the map possesses globally optimal characteristics. Additionally, it is demonstrated that the dynamically optimal F yields T map can be modified so that the robot redundancy is used to simultaneously improve the dynamic response and realize any specified kinematic performance objective (e.g., manipulability maximization or obstacle avoidance). Computer simulation results are given for a four degree of freedom planar redundant robot under Cartesian control, and demonstrate that position/force trajectory tracking and effective redundancy utilization can be achieved simultaneously with the proposed controller.

  15. Fault tolerance in protein interaction networks: stable bipartite subgraphs and redundant pathways.

    PubMed

    Brady, Arthur; Maxwell, Kyle; Daniels, Noah; Cowen, Lenore J

    2009-01-01

    As increasing amounts of high-throughput data for the yeast interactome become available, more system-wide properties are uncovered. One interesting question concerns the fault tolerance of protein interaction networks: whether there exist alternative pathways that can perform some required function if a gene essential to the main mechanism is defective, absent or suppressed. A signature pattern for redundant pathways is the BPM (between-pathway model) motif, introduced by Kelley and Ideker. Past methods proposed to search the yeast interactome for BPM motifs have had several important limitations. First, they have been driven heuristically by local greedy searches, which can lead to the inclusion of extra genes that may not belong in the motif; second, they have been validated solely by functional coherence of the putative pathways using GO enrichment, making it difficult to evaluate putative BPMs in the absence of already known biological annotation. We introduce stable bipartite subgraphs, and show they form a clean and efficient way of generating meaningful BPMs which naturally discard extra genes included by local greedy methods. We show by GO enrichment measures that our BPM set outperforms previous work, covering more known complexes and functional pathways. Perhaps most importantly, since our BPMs are initially generated by examining the genetic-interaction network only, the location of edges in the protein-protein physical interaction network can then be used to statistically validate each candidate BPM, even with sparse GO annotation (or none at all). We uncover some interesting biological examples of previously unknown putative redundant pathways in such areas as vesicle-mediated transport and DNA repair.

  16. Fault Tolerance in Protein Interaction Networks: Stable Bipartite Subgraphs and Redundant Pathways

    PubMed Central

    Brady, Arthur; Maxwell, Kyle; Daniels, Noah; Cowen, Lenore J.

    2009-01-01

    As increasing amounts of high-throughput data for the yeast interactome become available, more system-wide properties are uncovered. One interesting question concerns the fault tolerance of protein interaction networks: whether there exist alternative pathways that can perform some required function if a gene essential to the main mechanism is defective, absent or suppressed. A signature pattern for redundant pathways is the BPM (between-pathway model) motif, introduced by Kelley and Ideker. Past methods proposed to search the yeast interactome for BPM motifs have had several important limitations. First, they have been driven heuristically by local greedy searches, which can lead to the inclusion of extra genes that may not belong in the motif; second, they have been validated solely by functional coherence of the putative pathways using GO enrichment, making it difficult to evaluate putative BPMs in the absence of already known biological annotation. We introduce stable bipartite subgraphs, and show they form a clean and efficient way of generating meaningful BPMs which naturally discard extra genes included by local greedy methods. We show by GO enrichment measures that our BPM set outperforms previous work, covering more known complexes and functional pathways. Perhaps most importantly, since our BPMs are initially generated by examining the genetic-interaction network only, the location of edges in the protein-protein physical interaction network can then be used to statistically validate each candidate BPM, even with sparse GO annotation (or none at all). We uncover some interesting biological examples of previously unknown putative redundant pathways in such areas as vesicle-mediated transport and DNA repair. PMID:19399174

  17. Development of an automatic subsea blowout preventer stack control system using PLC based SCADA.

    PubMed

    Cai, Baoping; Liu, Yonghong; Liu, Zengkai; Wang, Fei; Tian, Xiaojie; Zhang, Yanzhen

    2012-01-01

    An extremely reliable remote control system for subsea blowout preventer stack is developed based on the off-the-shelf triple modular redundancy system. To meet a high reliability requirement, various redundancy techniques such as controller redundancy, bus redundancy and network redundancy are used to design the system hardware architecture. The control logic, human-machine interface graphical design and redundant databases are developed by using the off-the-shelf software. A series of experiments were performed in laboratory to test the subsea blowout preventer stack control system. The results showed that the tested subsea blowout preventer functions could be executed successfully. For the faults of programmable logic controllers, discrete input groups and analog input groups, the control system could give correct alarms in the human-machine interface. Copyright © 2011 ISA. Published by Elsevier Ltd. All rights reserved.

  18. Kinematic functions for redundancy resolution using configuration control

    NASA Technical Reports Server (NTRS)

    Seraji, Homayoun (Inventor)

    1994-01-01

    The invention fulfills new goals for redundancy resolution based on manipulator dynamics and end-effector characteristics. These goals are accomplished by employing the recently developed configuration control approach. Redundancy resolution is achieved by controlling the joint inertia matrix of the end-effector mass matrix that affect the inertial torques or by reducing the joint torques due to gravity loading and payload. The manipulator mechanical-advantage and velocity-ratio are also used as performance measures to be improved by proper utilization of redundancy. Furthermore, end-effector compliance, sensitivity, and impulsive force at impact are introduced as redundancy resolution criteria. The new goals for redundancy resolution allow a more efficient utilization of the redundant joints based on the desired task requirements.

  19. Mature neurons dynamically restrict apoptosis via redundant premitochondrial brakes.

    PubMed

    Annis, Ryan P; Swahari, Vijay; Nakamura, Ayumi; Xie, Alison X; Hammond, Scott M; Deshmukh, Mohanish

    2016-12-01

    Apoptotic cell death is critical for the early development of the nervous system, but once the nervous system is established, the apoptotic pathway becomes highly restricted in mature neurons. However, the mechanisms underlying this increased resistance to apoptosis in these mature neurons are not completely understood. We have previously found that members of the miR-29 family of microRNAs (miRNAs) are induced with neuronal maturation and that overexpression of miR-29 was sufficient to restrict apoptosis in neurons. To determine whether endogenous miR-29 alone was responsible for the inhibition of cytochrome c release in mature neurons, we examined the status of the apoptotic pathway in sympathetic neurons deficient for all three miR-29 family members. Unexpectedly, we found that the apoptotic pathway remained largely restricted in miR-29-deficient mature neurons. We therefore probed for additional mechanisms by which mature neurons resist apoptosis. We identify miR-24 as another miRNA that is upregulated in the maturing cerebellum and sympathetic neurons that can act redundantly with miR-29 by targeting a similar repertoire of prodeath BH3-only genes. Overall, our results reveal that mature neurons engage multiple redundant brakes to restrict the apoptotic pathway and ensure their long-term survival. © 2016 Federation of European Biochemical Societies.

  20. The evolution of plant virus transmission pathways

    Treesearch

    Frédéric M. Hamelin; Linda J.S. Allen; Holly R. Prendeville; M. Reza Hajimorad; Michael J. Jeger

    2016-01-01

    The evolution of plant virus transmission pathways is studied through transmission via seed, pollen, oravector. We address the questions: under what circumstances does vector transmission make pollen transmission redundant? Can evolution lead to the coexistence of multiple virus transmission pathways? We restrict the analysis to an annual plant population in which...

  1. Redundant information encoding in primary motor cortex during natural and prosthetic motor control.

    PubMed

    So, Kelvin; Ganguly, Karunesh; Jimenez, Jessica; Gastpar, Michael C; Carmena, Jose M

    2012-06-01

    Redundant encoding of information facilitates reliable distributed information processing. To explore this hypothesis in the motor system, we applied concepts from information theory to quantify the redundancy of movement-related information encoded in the macaque primary motor cortex (M1) during natural and neuroprosthetic control. Two macaque monkeys were trained to perform a delay center-out reaching task controlling a computer cursor under natural arm movement (manual control, 'MC'), and using a brain-machine interface (BMI) via volitional control of neural ensemble activity (brain control, 'BC'). During MC, we found neurons in contralateral M1 to contain higher and more redundant information about target direction than ipsilateral M1 neurons, consistent with the laterality of movement control. During BC, we found that the M1 neurons directly incorporated into the BMI ('direct' neurons) contained the highest and most redundant target information compared to neurons that were not incorporated into the BMI ('indirect' neurons). This effect was even more significant when comparing to M1 neurons of the opposite hemisphere. Interestingly, when we retrained the BMI to use ipsilateral M1 activity, we found that these neurons were more redundant and contained higher information than contralateral M1 neurons, even though ensembles from this hemisphere were previously less redundant during natural arm movement. These results indicate that ensembles most associated to movement contain highest redundancy and information encoding, which suggests a role for redundancy in proficient natural and prosthetic motor control.

  2. Pathway redundancy and protein essentiality revealed in the Saccharomyces cerevisiae interaction networks

    PubMed Central

    Ulitsky, Igor; Shamir, Ron

    2007-01-01

    The biological interpretation of genetic interactions is a major challenge. Recently, Kelley and Ideker proposed a method to analyze together genetic and physical networks, which explains many of the known genetic interactions as linking different pathways in the physical network. Here, we extend this method and devise novel analytic tools for interpreting genetic interactions in a physical context. Applying these tools on a large-scale Saccharomyces cerevisiae data set, our analysis reveals 140 between-pathway models that explain 3765 genetic interactions, roughly doubling those that were previously explained. Model genes tend to have short mRNA half-lives and many phosphorylation sites, suggesting that their stringent regulation is linked to pathway redundancy. We also identify ‘pivot' proteins that have many physical interactions with both pathways in our models, and show that pivots tend to be essential and highly conserved. Our analysis of models and pivots sheds light on the organization of the cellular machinery as well as on the roles of individual proteins. PMID:17437029

  3. Characterization and control of self-motions in redundant manipulators

    NASA Technical Reports Server (NTRS)

    Burdick, J.; Seraji, Homayoun

    1989-01-01

    The presence of redundant degrees of freedom in a manipulator structure leads to a physical phenomenon known as a self-motion, which is a continuous motion of the manipulator joints that leaves the end-effector motionless. In the first part of the paper, a global manifold mapping reformulation of manipulator kinematics is reviewed, and the inverse kinematic solution for redundant manipulators is developed in terms of self-motion manifolds. Global characterizations of the self-motion manifolds in terms of their number, geometry, homotopy class, and null space are reviewed using examples. Much previous work in redundant manipulator control has been concerned with the redundancy resolution problem, in which methods are developed to determine, or resolve, the motion of the joints in order to achieve end-effector trajectory control while optimizing additional objective functions. Redundancy resolution problems can be equivalently posed as the control of self-motions. Alternatives for redundancy resolution are briefly discussed.

  4. Learning visuomotor transformations for gaze-control and grasping.

    PubMed

    Hoffmann, Heiko; Schenck, Wolfram; Möller, Ralf

    2005-08-01

    For reaching to and grasping of an object, visual information about the object must be transformed into motor or postural commands for the arm and hand. In this paper, we present a robot model for visually guided reaching and grasping. The model mimics two alternative processing pathways for grasping, which are also likely to coexist in the human brain. The first pathway directly uses the retinal activation to encode the target position. In the second pathway, a saccade controller makes the eyes (cameras) focus on the target, and the gaze direction is used instead as positional input. For both pathways, an arm controller transforms information on the target's position and orientation into an arm posture suitable for grasping. For the training of the saccade controller, we suggest a novel staged learning method which does not require a teacher that provides the necessary motor commands. The arm controller uses unsupervised learning: it is based on a density model of the sensor and the motor data. Using this density, a mapping is achieved by completing a partially given sensorimotor pattern. The controller can cope with the ambiguity in having a set of redundant arm postures for a given target. The combined model of saccade and arm controller was able to fixate and grasp an elongated object with arbitrary orientation and at arbitrary position on a table in 94% of trials.

  5. Evaluating between-pathway models with expression data.

    PubMed

    Hescott, B J; Leiserson, M D M; Cowen, L J; Slonim, D K

    2010-03-01

    Between-pathway models (BPMs) are network motifs consisting of pairs of putative redundant pathways. In this article, we show how adding another source of high-throughput data--microarray gene expression data from knockout experiments--allows us to identify a compensatory functional relationship between genes from the two BPM pathways. We evaluate the quality of the BPMs from four different studies, and we describe how our methods might be extended to refine pathways.

  6. Evaluating Between-Pathway Models with Expression Data

    PubMed Central

    Leiserson, M.D.M.; Cowen, L.J.; Slonim, D.K.

    2010-01-01

    Abstract Between-pathway models (BPMs) are network motifs consisting of pairs of putative redundant pathways. In this article, we show how adding another source of high-throughput data—microarray gene expression data from knockout experiments—allows us to identify a compensatory functional relationship between genes from the two BPM pathways. We evaluate the quality of the BPMs from four different studies, and we describe how our methods might be extended to refine pathways. PMID:20377458

  7. Characterizing metabolic pathway diversification in the context of perturbation size.

    PubMed

    Yang, Laurence; Srinivasan, Shyamsundhar; Mahadevan, Radhakrishnan; Cluett, William R

    2015-03-01

    Cell metabolism is an important platform for sustainable biofuel, chemical and pharmaceutical production but its complexity presents a major challenge for scientists and engineers. Although in silico strains have been designed in the past with predicted performances near the theoretical maximum, real-world performance is often sub-optimal. Here, we simulate how strain performance is impacted when subjected to many randomly varying perturbations, including discrepancies between gene expression and in vivo flux, osmotic stress, and substrate uptake perturbations due to concentration gradients in bioreactors. This computational study asks whether robust performance can be achieved by adopting robustness-enhancing mechanisms from naturally evolved organisms-in particular, redundancy. Our study shows that redundancy, typically perceived as a ubiquitous robustness-enhancing strategy in nature, can either improve or undermine robustness depending on the magnitude of the perturbations. We also show that the optimal number of redundant pathways used can be predicted for a given perturbation size. Copyright © 2015. Published by Elsevier Inc.

  8. Refinement of light-responsive transcript lists using rice oligonucleotide arrays: evaluation of gene-redundancy.

    PubMed

    Jung, Ki-Hong; Dardick, Christopher; Bartley, Laura E; Cao, Peijian; Phetsom, Jirapa; Canlas, Patrick; Seo, Young-Su; Shultz, Michael; Ouyang, Shu; Yuan, Qiaoping; Frank, Bryan C; Ly, Eugene; Zheng, Li; Jia, Yi; Hsia, An-Ping; An, Kyungsook; Chou, Hui-Hsien; Rocke, David; Lee, Geun Cheol; Schnable, Patrick S; An, Gynheung; Buell, C Robin; Ronald, Pamela C

    2008-10-06

    Studies of gene function are often hampered by gene-redundancy, especially in organisms with large genomes such as rice (Oryza sativa). We present an approach for using transcriptomics data to focus functional studies and address redundancy. To this end, we have constructed and validated an inexpensive and publicly available rice oligonucleotide near-whole genome array, called the rice NSF45K array. We generated expression profiles for light- vs. dark-grown rice leaf tissue and validated the biological significance of the data by analyzing sources of variation and confirming expression trends with reverse transcription polymerase chain reaction. We examined trends in the data by evaluating enrichment of gene ontology terms at multiple false discovery rate thresholds. To compare data generated with the NSF45K array with published results, we developed publicly available, web-based tools (www.ricearray.org). The Oligo and EST Anatomy Viewer enables visualization of EST-based expression profiling data for all genes on the array. The Rice Multi-platform Microarray Search Tool facilitates comparison of gene expression profiles across multiple rice microarray platforms. Finally, we incorporated gene expression and biochemical pathway data to reduce the number of candidate gene products putatively participating in the eight steps of the photorespiration pathway from 52 to 10, based on expression levels of putatively functionally redundant genes. We confirmed the efficacy of this method to cope with redundancy by correctly predicting participation in photorespiration of a gene with five paralogs. Applying these methods will accelerate rice functional genomics.

  9. Optimization of robustness of interdependent network controllability by redundant design

    PubMed Central

    2018-01-01

    Controllability of complex networks has been a hot topic in recent years. Real networks regarded as interdependent networks are always coupled together by multiple networks. The cascading process of interdependent networks including interdependent failure and overload failure will destroy the robustness of controllability for the whole network. Therefore, the optimization of the robustness of interdependent network controllability is of great importance in the research area of complex networks. In this paper, based on the model of interdependent networks constructed first, we determine the cascading process under different proportions of node attacks. Then, the structural controllability of interdependent networks is measured by the minimum driver nodes. Furthermore, we propose a parameter which can be obtained by the structure and minimum driver set of interdependent networks under different proportions of node attacks and analyze the robustness for interdependent network controllability. Finally, we optimize the robustness of interdependent network controllability by redundant design including node backup and redundancy edge backup and improve the redundant design by proposing different strategies according to their cost. Comparative strategies of redundant design are conducted to find the best strategy. Results shows that node backup and redundancy edge backup can indeed decrease those nodes suffering from failure and improve the robustness of controllability. Considering the cost of redundant design, we should choose BBS (betweenness-based strategy) or DBS (degree based strategy) for node backup and HDF(high degree first) for redundancy edge backup. Above all, our proposed strategies are feasible and effective at improving the robustness of interdependent network controllability. PMID:29438426

  10. Assessing the evolution of redundancy/synergy of spontaneous variability regulation with age.

    PubMed

    Porta, Alberto; Bari, Vlasta; De Maria, Beatrice; Perseguini, Natália M; Milan, Juliana; Rehder-Santos, Patricia; Minatel, Vinícius; Takahashi, Anielle C M; Catai, Aparecida M

    2017-05-01

    We exploited a model-based Wiener-Granger causality method in the information domain for the evaluation of the transfer entropy (TE) and interaction TE (ITE), the latter taken as a measure of the net balance between redundancy and synergy, to describe the interactions between the spontaneous variability of heart period (HP) and systolic arterial pressure (SAP) and the effect of respiration (R) on both variables. Cardiac control was typified via the genuine TE from SAP to HP, that from R to HP, and the ITE from SAP and R to HP, while vascular control was characterized via the genuine TE from HP to SAP, that from R to SAP, and the ITE from HP and R to SAP. The approach was applied to study age-related modifications of cardiac and vascular controls in a cohort of 100 healthy humans (age from 21 to 70 years, 54 males) recorded at supine rest (REST) and during active standing (STAND). A surrogate approach was exploited to test the significance of the computed quantities. Trends of the genuine information transfer with age, already present in literature, were here confirmed. We originally found that: (i) at REST redundancy was predominant over synergy in both vascular and cardiac controls; (ii) the predominance of redundancy of the cardiac control was not affected by postural challenge, while STAND reduced redundancy of vascular control; (iii) the net redundancy of the cardiac control at REST gradually decreased with age, while that of vascular control remained stable; (iv) during STAND net redundancy of both cardiac and vascular controls was stable with age. The study confirms the relevance of computing genuine information transfer in cardiovascular control analysis and stresses the importance of evaluating the ITE to quantify the degree of redundancy of physiological mechanisms operating to maintain cardiovascular homeostasis.

  11. Configuration-Control Scheme Copes With Singularities

    NASA Technical Reports Server (NTRS)

    Seraji, Homayoun; Colbaugh, Richard D.

    1993-01-01

    Improved configuration-control scheme for robotic manipulator having redundant degrees of freedom suppresses large joint velocities near singularities, at expense of small trajectory errors. Provides means to enforce order of priority of tasks assigned to robot. Basic concept of configuration control of redundant robot described in "Increasing The Dexterity Of Redundant Robots" (NPO-17801).

  12. Reliability of Fault Tolerant Control Systems. Part 2

    NASA Technical Reports Server (NTRS)

    Wu, N. Eva

    2000-01-01

    This paper reports Part II of a two part effort that is intended to delineate the relationship between reliability and fault tolerant control in a quantitative manner. Reliability properties peculiar to fault-tolerant control systems are emphasized, such as the presence of analytic redundancy in high proportion, the dependence of failures on control performance, and high risks associated with decisions in redundancy management due to multiple sources of uncertainties and sometimes large processing requirements. As a consequence, coverage of failures through redundancy management can be severely limited. The paper proposes to formulate the fault tolerant control problem as an optimization problem that maximizes coverage of failures through redundancy management. Coverage modeling is attempted in a way that captures its dependence on the control performance and on the diagnostic resolution. Under the proposed redundancy management policy, it is shown that an enhanced overall system reliability can be achieved with a control law of a superior robustness, with an estimator of a higher resolution, and with a control performance requirement of a lesser stringency.

  13. Management of redundancy in flight control systems using optimal decision theory

    NASA Technical Reports Server (NTRS)

    1981-01-01

    The problem of using redundancy that exists between dissimilar systems in aircraft flight control is addressed. That is, using the redundancy that exists between a rate gyro and an accelerometer--devices that have dissimilar outputs which are related only through the dynamics of the aircraft motion. Management of this type of redundancy requires advanced logic so that the system can monitor failure status and can reconfigure itself in the event of one or more failures. An optimal decision theory was tutorially developed for the management of sensor redundancy and the theory is applied to two aircraft examples. The first example is the space shuttle and the second is a highly maneuvering high performance aircraft--the F8-C. The examples illustrate the redundancy management design process and the performance of the algorithms presented in failure detection and control law reconfiguration.

  14. Analyzing cell fate control by cytokines through continuous single cell biochemistry.

    PubMed

    Rieger, Michael A; Schroeder, Timm

    2009-10-01

    Cytokines are important regulators of cell fates with high clinical and commercial relevance. However, despite decades of intense academic and industrial research, it proved surprisingly difficult to describe the biological functions of cytokines in a precise and comprehensive manner. The exact analysis of cytokine biology is complicated by the fact that individual cytokines control many different cell fates and activate a multitude of intracellular signaling pathways. Moreover, although activating different molecular programs, different cytokines can be redundant in their biological effects. In addition, cytokines with different biological effects can activate overlapping signaling pathways. This prospect article will outline the necessity of continuous single cell biochemistry to unravel the biological functions of molecular cytokine signaling. It focuses on potentials and limitations of recent technical developments in fluorescent time-lapse imaging and single cell tracking allowing constant long-term observation of molecules and behavior of single cells. (c) 2009 Wiley-Liss, Inc.

  15. Neuroendocrine integration of nutritional signals on reproduction.

    PubMed

    Evans, Maggie C; Anderson, Greg M

    2017-02-01

    Reproductive function in mammals is energetically costly and therefore tightly regulated by nutritional status. To enable this integration of metabolic and reproductive function, information regarding peripheral nutritional status must be relayed centrally to the gonadotropin-releasing hormone (GNRH) neurons that drive reproductive function. The metabolically relevant hormones leptin, insulin and ghrelin have been identified as key mediators of this 'metabolic control of fertility'. However, the neural circuitry through which they act to exert their control over GNRH drive remains incompletely understood. With the advent of Cre-LoxP technology, it has become possible to perform targeted gene-deletion and gene-rescue experiments and thus test the functional requirement and sufficiency, respectively, of discrete hormone-neuron signaling pathways in the metabolic control of reproductive function. This review discusses the findings from these investigations, and attempts to put them in context with what is known from clinical situations and wild-type animal models. What emerges from this discussion is clear evidence that the integration of nutritional signals on reproduction is complex and highly redundant, and therefore, surprisingly difficult to perturb. Consequently, the deletion of individual hormone-neuron signaling pathways often fails to cause reproductive phenotypes, despite strong evidence that the targeted pathway plays a role under normal physiological conditions. Although transgenic studies rarely reveal a critical role for discrete signaling pathways, they nevertheless prove to be a good strategy for identifying whether a targeted pathway is absolutely required, critically involved, sufficient or dispensable in the metabolic control of fertility. © 2017 Society for Endocrinology.

  16. Analysis of protein interactions within the cytokinin-signaling pathway of Arabidopsis thaliana.

    PubMed

    Dortay, Hakan; Mehnert, Nijuscha; Bürkle, Lukas; Schmülling, Thomas; Heyl, Alexander

    2006-10-01

    The signal of the plant hormone cytokinin is perceived by membrane-located sensor histidine kinases and transduced by other members of the plant two-component system. In Arabidopsis thaliana, 28 two-component system proteins (phosphotransmitters and response regulators) act downstream of three receptors, transmitting the signal from the membrane to the nucleus and modulating the cellular response. Although the principal signaling mechanism has been elucidated, redundancy in the system has made it difficult to understand which of the many components interact to control the downstream biological processes. Here, we present a large-scale interaction study comprising most members of the Arabidopsis cytokinin signaling pathway. Using the yeast two-hybrid system, we detected 42 new interactions, of which more than 90% were confirmed by in vitro coaffinity purification. There are distinct patterns of interaction between protein families, but only a few interactions between proteins of the same family. An interaction map of this signaling pathway shows the Arabidopsis histidine phosphotransfer proteins as hubs, which interact with members from all other protein families, mostly in a redundant fashion. Domain-mapping experiments revealed the interaction domains of the proteins of this pathway. Analyses of Arabidopsis histidine phosphotransfer protein 5 mutant proteins showed that the presence of the canonical phospho-accepting histidine residue is not required for the interactions. Interaction of A-type response regulators with Arabidopsis histidine phosphotransfer proteins but not with B-type response regulators suggests that their known activity in feedback regulation may be realized by interfering at the level of Arabidopsis histidine phosphotransfer protein-mediated signaling. This study contributes to our understanding of the protein interactions of the cytokinin-signaling system and provides a framework for further functional studies in planta.

  17. Application of redundancy in the Saturn 5 guidance and control system

    NASA Technical Reports Server (NTRS)

    Moore, F. B.; White, J. B.

    1976-01-01

    The Saturn launch vehicle's guidance and control system is so complex that the reliability of a simplex system is not adequate to fulfill mission requirements. Thus, to achieve the desired reliability, redundancy encompassing a wide range of types and levels was employed. At one extreme, the lowest level, basic components (resistors, capacitors, relays, etc.) are employed in series, parallel, or quadruplex arrangements to insure continued system operation in the presence of possible failure conditions. At the other extreme, the highest level, complete subsystem duplication is provided so that a backup subsystem can be employed in case the primary system malfunctions. In between these two extremes, many other redundancy schemes and techniques are employed at various levels. Basic redundancy concepts are covered to gain insight into the advantages obtained with various techniques. Points and methods of application of these techniques are included. The theoretical gain in reliability resulting from redundancy is assessed and compared to a simplex system. Problems and limitations encountered in the practical application of redundancy are discussed as well as techniques verifying proper operation of the redundant channels. As background for the redundancy application discussion, a basic description of the guidance and control system is included.

  18. Increasing The Dexterity Of Redundant Robots

    NASA Technical Reports Server (NTRS)

    Seraji, Homayoun

    1990-01-01

    Redundant coordinates used to define additional tasks. Configuration control emerging as effective way to control motions of robot having more degrees of freedom than necessary to define trajectory of end effector and/or of object to be manipulated. Extra or redundant degrees of freedom used to give robot humanlike dexterity and versatility.

  19. Redundant Asynchronous Microprocessor System

    NASA Technical Reports Server (NTRS)

    Meyer, G.; Johnston, J. O.; Dunn, W. R.

    1985-01-01

    Fault-tolerant computer structure called RAMPS (for redundant asynchronous microprocessor system) has simplicity of static redundancy but offers intermittent-fault handling ability of complex, dynamically redundant systems. New structure useful wherever several microprocessors are employed for control - in aircraft, industrial processes, robotics, and automatic machining, for example.

  20. ESTs from Seeds to Assist the Selective Breeding of Jatropha curcas L. for Oil and Active Compounds

    PubMed Central

    Gomes, Kleber A; Almeida, Tiago C; Gesteira, Abelmon S; Lôbo, Ivon P; Guimarães, Ana Carolina R; de Miranda, Antonio B; Van Sluys, Marie-Anne; da Cruz, Rosenira S; Cascardo, Júlio CM; Carels, Nicolas

    2010-01-01

    We report here on the characterization of a cDNA library from seeds of Jatropha curcas L. at three stages of fruit maturation before yellowing. We sequenced a total of 2200 clones and obtained a set of 931 non-redundant sequences (unigenes) after trimming and quality control, ie, 140 contigs and 791 singlets with PHRED quality ≥10. We found low levels of sequence redundancy and extensive metabolic coverage by homology comparison to GO. After comparison of 5841 non-redundant ESTs from a total of 13193 reads from GenBank with KEGG, we identified tags with nucleotide variations among J. curcas accessions for genes of fatty acid, terpene, alkaloid, quinone and hormone pathways of biosynthesis. More specifically, the expression level of four genes (palmitoyl-acyl carrier protein thioesterase, 3-ketoacyl-CoA thiolase B, lysophosphatidic acid acyltransferase and geranyl pyrophosphate synthase) measured by real-time PCR proved to be significantly different between leaves and fruits. Since the nucleotide polymorphism of these tags is associated to higher level of gene expression in fruits compared to leaves, we propose this approach to speed up the search for quantitative traits in selective breeding of J. curcas. We also discuss its potential utility for the selective breeding of economically important traits in J. curcas. PMID:26217103

  1. A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress

    PubMed Central

    McMurchy, Alicia N; Stempor, Przemyslaw; Gaarenstroom, Tessa; Wysolmerski, Brian; Dong, Yan; Aussianikava, Darya; Appert, Alex; Huang, Ni; Kolasinska-Zwierz, Paulina; Sapetschnig, Alexandra; Miska, Eric A; Ahringer, Julie

    2017-01-01

    Repetitive sequences derived from transposons make up a large fraction of eukaryotic genomes and must be silenced to protect genome integrity. Repetitive elements are often found in heterochromatin; however, the roles and interactions of heterochromatin proteins in repeat regulation are poorly understood. Here we show that a diverse set of C. elegans heterochromatin proteins act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. Mutants in genes encoding HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2, and H3K9me2 histone methyltransferase MET-2/SETDB1 also show functionally redundant sterility, increased germline apoptosis, DNA repair defects, and interactions with small RNA pathways. Remarkably, fertility of heterochromatin mutants could be partially restored by inhibiting cep-1/p53, endogenous meiotic double strand breaks, or the expression of MIRAGE1 DNA transposons. Functional redundancy among factors and pathways underlies the importance of safeguarding the genome through multiple means. DOI: http://dx.doi.org/10.7554/eLife.21666.001 PMID:28294943

  2. Regulatory RNAs and the HptB/RetS signalling pathways fine-tune Pseudomonas aeruginosa pathogenesis

    PubMed Central

    Bordi, Christophe; Lamy, Marie-Cécile; Ventre, Isabelle; Termine, Elise; Hachani, Abderrahman; Fillet, Sandy; Roche, Béatrice; Bleves, Sophie; Méjean, Vincent; Lazdunski, Andrée; Filloux, Alain

    2010-01-01

    Bacterial pathogenesis often depends on regulatory networks, two-component systems and small RNAs (sRNAs). In Pseudomonas aeruginosa, the RetS sensor pathway downregulates expression of two sRNAs, rsmY and rsmZ. Consequently, biofilm and the Type Six Secretion System (T6SS) are repressed, whereas the Type III Secretion System (T3SS) is activated. We show that the HptB signalling pathway controls biofilm and T3SS, and fine-tunes P. aeruginosa pathogenesis. We demonstrate that RetS and HptB intersect at the GacA response regulator, which directly controls sRNAs production. Importantly, RetS controls both sRNAs, whereas HptB exclusively regulates rsmY expression. We reveal that HptB signalling is a complex regulatory cascade. This cascade involves a response regulator, with an output domain belonging to the phosphatase 2C family, and likely an anti-anti-σ factor. This reveals that the initial input in the Gac system comes from several signalling pathways, and the final output is adjusted by a differential control on rsmY and rsmZ. This is exemplified by the RetS-dependent but HptB-independent control on T6SS. We also demonstrate a redundant action of the two sRNAs on T3SS gene expression, while the impact on pel gene expression is additive. These features underpin a novel mechanism in the fine-tuned regulation of gene expression. PMID:20398205

  3. AFTI/F-111 MAW flight control system and redundancy management description

    NASA Technical Reports Server (NTRS)

    Larson, Richard R.

    1987-01-01

    The wing on the NASA F-111 transonic aircraft technology (TACT) airplane was modified to provide flexible leading and trailing edge flaps; this modified wing is known as the mission adaptive wing (MAW). A dual digital primary fly-by-wire flight control system was developed with analog backup reversion for redundancy. This report discusses the functions, design, and redundancy management of the flight control system for these flaps.

  4. Co-Targeting HER2 and EphB4 Pathways

    DTIC Science & Technology

    2013-09-01

    soluble EphB4 decoy receptor that efficiently blocks EphB4/EphB2 signaling. A phase I study for solid tumors using this agent given intravenously...June 2013 3 . DATES COVERED 4. TITLE AND SUBTITLE Co-Targeting HER2 and EphB4 Pathways 5a. CONTRACT NUMBER W81XWH-11-1-0471 5b. GRANT...13. SUPPLEMENTARY NOTES 14. ABSTRACT Multiple receptor pathways allow for redundancy in growth pathways that are dysregulated in cancer and lead to

  5. Estrogen alters the profile of the transcriptome in river snail Bellamya aeruginosa.

    PubMed

    Lei, Kun; Liu, Ruizhi; An, Li-Hui; Luo, Ying-Feng; LeBlanc, Gerald A

    2015-03-01

    We evaluated the transcriptome dynamics of the freshwater river snail Bellamya aeruginosa exposed to 17β-estradiol (E2) using the Roche/454 GS-FLX platform. In total, 41,869 unigenes, with an average length of 586 bp, representing 36,181 contigs and 5,688 singlets were obtained. Among them, 18.08, 36.85, and 25.47 % matched sequences in the GenBank non-redundant nucleic acid database, non-redundant protein database, and Swiss protein database, respectively. Annotation of the unigenes with gene ontology, and then mapping them to biological pathways, revealed large groups of genes related to growth, development, reproduction, signal transduction, and defense mechanisms. Significant differences were found in gene expression in both liver and testicular tissues between control and E2-exposed organisms. These changes in gene expression will help in understanding the molecular mechanisms of the response to physiological stress in the river snail exposed to estrogen, and will facilitate research into biological processes and underlying physiological adaptations to xenoestrogen exposure in gastropods.

  6. Learning Contrast-Invariant Cancellation of Redundant Signals in Neural Systems

    PubMed Central

    Bol, Kieran; Maler, Leonard; Longtin, André

    2013-01-01

    Cancellation of redundant information is a highly desirable feature of sensory systems, since it would potentially lead to a more efficient detection of novel information. However, biologically plausible mechanisms responsible for such selective cancellation, and especially those robust to realistic variations in the intensity of the redundant signals, are mostly unknown. In this work, we study, via in vivo experimental recordings and computational models, the behavior of a cerebellar-like circuit in the weakly electric fish which is known to perform cancellation of redundant stimuli. We experimentally observe contrast invariance in the cancellation of spatially and temporally redundant stimuli in such a system. Our model, which incorporates heterogeneously-delayed feedback, bursting dynamics and burst-induced STDP, is in agreement with our in vivo observations. In addition, the model gives insight on the activity of granule cells and parallel fibers involved in the feedback pathway, and provides a strong prediction on the parallel fiber potentiation time scale. Finally, our model predicts the existence of an optimal learning contrast around 15% contrast levels, which are commonly experienced by interacting fish. PMID:24068898

  7. Redundant arm control in a supervisory and shared control system

    NASA Technical Reports Server (NTRS)

    Backes, Paul G.; Long, Mark K.

    1992-01-01

    The Extended Task Space Control approach to robotic operations based on manipulator behaviors derived from task requirements is described. No differentiation between redundant and non-redundant robots is made at the task level. The manipulation task behaviors are combined into a single set of motion commands. The manipulator kinematics are used subsequently in mapping motion commands into actuator commands. Extended Task Space Control is applied to a Robotics Research K-1207 seven degree-of-freedom manipulator in a supervisory telerobot system as an example.

  8. A structural model of the VEGF signalling pathway: emergence of robustness and redundancy properties.

    PubMed

    Lignet, Floriane; Calvez, Vincent; Grenier, Emmanuel; Ribba, Benjamin

    2013-02-01

    The vascular endothelial growth factor (VEGF) is known as one of the main promoter of angiogenesis - the process of blood vessel formation. Angiogenesis has been recognized as a key stage for cancer development and metastasis. In this paper, we propose a structural model of the main molecular pathways involved in the endothelial cells response to VEGF stimuli. The model, built on qualitative information from knowledge databases, is composed of 38 ordinary differential equations with 78 parameters and focuses on the signalling driving endothelial cell proliferation, migration and resistance to apoptosis. Following a VEGF stimulus, the model predicts an increase of proliferation and migration capability, and a decrease in the apoptosis activity. Model simulations and sensitivity analysis highlight the emergence of robustness and redundancy properties of the pathway. If further calibrated and validated, this model could serve as tool to analyse and formulate new hypothesis on th e VEGF signalling cascade and its role in cancer development and treatment.

  9. PSD Camera Based Position and Posture Control of Redundant Robot Considering Contact Motion

    NASA Astrophysics Data System (ADS)

    Oda, Naoki; Kotani, Kentaro

    The paper describes a position and posture controller design based on the absolute position by external PSD vision sensor for redundant robot manipulator. The redundancy enables a potential capability to avoid obstacle while continuing given end-effector jobs under contact with middle link of manipulator. Under contact motion, the deformation due to joint torsion obtained by comparing internal and external position sensor, is actively suppressed by internal/external position hybrid controller. The selection matrix of hybrid loop is given by the function of the deformation. And the detected deformation is also utilized in the compliant motion controller for passive obstacle avoidance. The validity of the proposed method is verified by several experimental results of 3link planar redundant manipulator.

  10. Maximization of Learning Speed in the Motor Cortex Due to Neuronal Redundancy

    PubMed Central

    Takiyama, Ken; Okada, Masato

    2012-01-01

    Many redundancies play functional roles in motor control and motor learning. For example, kinematic and muscle redundancies contribute to stabilizing posture and impedance control, respectively. Another redundancy is the number of neurons themselves; there are overwhelmingly more neurons than muscles, and many combinations of neural activation can generate identical muscle activity. The functional roles of this neuronal redundancy remains unknown. Analysis of a redundant neural network model makes it possible to investigate these functional roles while varying the number of model neurons and holding constant the number of output units. Our analysis reveals that learning speed reaches its maximum value if and only if the model includes sufficient neuronal redundancy. This analytical result does not depend on whether the distribution of the preferred direction is uniform or a skewed bimodal, both of which have been reported in neurophysiological studies. Neuronal redundancy maximizes learning speed, even if the neural network model includes recurrent connections, a nonlinear activation function, or nonlinear muscle units. Furthermore, our results do not rely on the shape of the generalization function. The results of this study suggest that one of the functional roles of neuronal redundancy is to maximize learning speed. PMID:22253586

  11. Motion control of musculoskeletal systems with redundancy.

    PubMed

    Park, Hyunjoo; Durand, Dominique M

    2008-12-01

    Motion control of musculoskeletal systems for functional electrical stimulation (FES) is a challenging problem due to the inherent complexity of the systems. These include being highly nonlinear, strongly coupled, time-varying, time-delayed, and redundant. The redundancy in particular makes it difficult to find an inverse model of the system for control purposes. We have developed a control system for multiple input multiple output (MIMO) redundant musculoskeletal systems with little prior information. The proposed method separates the steady-state properties from the dynamic properties. The dynamic control uses a steady-state inverse model and is implemented with both a PID controller for disturbance rejection and an artificial neural network (ANN) feedforward controller for fast trajectory tracking. A mechanism to control the sum of the muscle excitation levels is also included. To test the performance of the proposed control system, a two degree of freedom ankle-subtalar joint model with eight muscles was used. The simulation results show that separation of steady-state and dynamic control allow small output tracking errors for different reference trajectories such as pseudo-step, sinusoidal and filtered random signals. The proposed control method also demonstrated robustness against system parameter and controller parameter variations. A possible application of this control algorithm is FES control using multiple contact cuff electrodes where mathematical modeling is not feasible and the redundancy makes the control of dynamic movement difficult.

  12. INVOLVED IN DE NOVO 2-containing complex involved in RNA-directed DNA methylation in Arabidopsis

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

    Ausin, Israel; Greenberg, Maxim V.C.; Simanshu, Dhirendra K.

    2012-10-23

    At least three pathways control maintenance of DNA cytosine methylation in Arabidopsis thaliana. However, the RNA-directed DNA methylation (RdDM) pathway is solely responsible for establishment of this silencing mark. We previously described INVOLVED IN DE NOVO 2 (IDN2) as being an RNA-binding RdDM component that is required for DNA methylation establishment. In this study, we describe the discovery of two partially redundant proteins that are paralogous to IDN2 and that form a stable complex with IDN2 in vivo. Null mutations in both genes, termed IDN2-LIKE 1 and IDN2-LIKE 2 (IDNL1 and IDNL2), result in a phenotype that mirrors, but doesmore » not further enhance, the idn2 mutant phenotype. Genetic analysis suggests that this complex acts in a step in the downstream portion of the RdDM pathway. We also have performed structural analysis showing that the IDN2 XS domain adopts an RNA recognition motif (RRM) fold. Finally, genome-wide DNA methylation and expression analysis confirms the placement of the IDN proteins in an RdDM pathway that affects DNA methylation and transcriptional control at many sites in the genome. Results from this study identify and describe two unique components of the RdDM machinery, adding to our understanding of DNA methylation control in the Arabidopsis genome.« less

  13. Summary report: A preliminary investigation into the use of fuzzy logic for the control of redundant manipulators

    NASA Technical Reports Server (NTRS)

    Cheatham, John B., Jr.; Magee, Kevin N.

    1991-01-01

    The Rice University Department of Mechanical Engineering and Materials Sciences' Robotics Group designed and built an eight degree of freedom redundant manipulator. Fuzzy logic was proposed as a control scheme for tasks not directly controlled by a human operator. In preliminary work, fuzzy logic control was implemented for a camera tracking system and a six degree of freedom manipulator. Both preliminary systems use real time vision data as input to fuzzy controllers. Related projects include integration of tactile sensing and fuzzy control of a redundant snake-like arm that is under construction.

  14. Redundant actuator development study. [flight control systems for supersonic transport aircraft

    NASA Technical Reports Server (NTRS)

    Ryder, D. R.

    1973-01-01

    Current and past supersonic transport configurations are reviewed to assess redundancy requirements for future airplane control systems. Secondary actuators used in stability augmentation systems will probably be the most critical actuator application and require the highest level of redundancy. Two methods of actuator redundancy mechanization have been recommended for further study. Math models of the recommended systems have been developed for use in future computer simulations. A long range plan has been formulated for actuator hardware development and testing in conjunction with the NASA Flight Simulator for Advanced Aircraft.

  15. A Method for Exploiting Redundancy to Accommodate Actuator Limits in Multivariable Systems

    NASA Technical Reports Server (NTRS)

    Litt, Jonathan; Roulette, Greg

    1995-01-01

    This paper introduces a new method for accommodating actuator saturation in a multivariable system with actuator redundancy. Actuator saturation can cause significant deterioration in control system performance because unmet demand may result in sluggish transients and oscillations in response to setpoint changes. To help compensate for this problem, a technique has been developed which takes advantage of redundancy in multivariable systems to redistribute the unmet control demand over the remaining useful effectors. This method is not a redesign procedure, rather it modifies commands to the unlimited effectors to compensate for those which are limited, thereby exploiting the built-in redundancy. The original commands are modified by the increments due to unmet demand, but when a saturated effector comes off its limit, the incremental commands disappear and the original unmodified controller remains intact. This scheme provides a smooth transition between saturated and unsaturated modes as it divides up the unmet requirement over any available actuators. This way, if there is sufficiently redundant control authority, performance can be maintained.

  16. Importin-7 Mediates Nuclear Trafficking of DNA in Mammalian Cells

    PubMed Central

    Dhanoya, Arjun; Wang, Tse; Keshavarz-Moore, Eli; Fassati, Ariberto; Chain, Benjamin M

    2013-01-01

    Eukaryotic cells have the ability to uptake and transport endogenous and exogenous DNA in their nuclei, however little is known about the specific pathways involved. Here we show that the nuclear transport receptor importin 7 (imp7) supports nuclear import of supercoiled plasmid DNA and human mitochondrial DNA in a Ran and energy-dependent way. The imp7-dependent pathway was specifically competed by excess DNA but not by excess of maltose-binding protein fused with the classical nuclear localizing signal (NLS) or the M9 peptides. Transport of DNA molecules complexed with poly-l-lysine was impaired in intact cells depleted of imp7, and DNA complexes remained localized in the cytoplasm. Poor DNA nuclear import in cells depleted of imp7 directly correlated with lower gene expression levels in these cells compared to controls. Inefficient nuclear import of transfected DNA induced greater upregulation of the interferon pathway, suggesting that rapid DNA nuclear import may prevent uncontrolled activation of the innate immune response. Our results provide evidence that imp7 is a non-redundant component of an intrinsic pathway in mammalian cells for efficient accumulation of exogenous and endogenous DNA in the nucleus, which may be critical for the exchange of genetic information between mitochondria and nuclear genomes and to control activation of the innate immune response. PMID:23067392

  17. Proteasomal Ubiquitin Receptor RPN-10 Controls Sex Determination in Caenorhabditis elegans

    PubMed Central

    Shimada, Masumi; Kanematsu, Kenji; Tanaka, Keiji; Yokosawa, Hideyoshi

    2006-01-01

    The ubiquitin-binding RPN-10 protein serves as a ubiquitin receptor that delivers client proteins to the 26S proteasome. Although ubiquitin recognition is an essential step for proteasomal destruction, deletion of the rpn-10 gene in yeast does not influence viability, indicating redundancy of the substrate delivery pathway. However, their specificity and biological relevance in higher eukaryotes is still enigmatic. We report herein that knockdown of the rpn-10 gene, but not any other proteasome subunit genes, sexually transforms hermaphrodites to females by eliminating hermaphrodite spermatogenesis in Caenorhabditis elegans. The feminization phenotype induced by deletion of the rpn-10 gene was rescued by knockdown of tra-2, one of sexual fate decision genes promoting female development, and its downstream target tra-1, indicating that the TRA-2–mediated sex determination pathway is crucial for the Δrpn-10–induced sterile phenotype. Intriguingly, we found that co-knockdown of rpn-10 and functionally related ubiquitin ligase ufd-2 overcomes the germline-musculinizing effect of fem-3(gf). Furthermore, TRA-2 proteins accumulated in rpn-10-defective worms. Our results show that the RPN-10–mediated ubiquitin pathway is indispensable for control of the TRA-2–mediated sex-determining pathway. PMID:17050737

  18. Control of B Lymphocyte Development and Functions by the mTOR Signaling Pathways

    PubMed Central

    Iwata, Terri N.; Ramírez-Komo, Julita A.; Park, Heon; Iritani, Brian M.

    2017-01-01

    Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase originally discovered as the molecular target of the immunosuppressant rapamycin. mTOR forms two compositionally and functionally distinct complexes, mTORC1 and mTORC2, which are crucial for coordinating nutrient, energy, oxygen, and growth factor availability with cellular growth, proliferation, and survival. Recent studies have identified critical, non-redundant roles for mTORC1 and mTORC2 in controlling B cell development, differentiation, and functions, and have highlighted emerging roles of the Folliculin-Fnip protein complex in regulating mTOR and B cell development. In this review, we summarize the basic mechanisms of mTOR signaling; describe what is known about the roles of mTORC1, mTORC2, and the Folliculin/Fnip1 pathway in B cell development and functions; and briefly outline current clinical approaches for targeting mTOR in B cell neoplasms. We conclude by highlighting a few salient questions and future perspectives regarding mTOR in B lineage cells. PMID:28583723

  19. Periodically Self Restoring Redundant Systems for VLSI Based Highly Reliable Design,

    DTIC Science & Technology

    1984-01-01

    fault tolerance technique for realizing highly reliable computer systems for critical control applications . However, VL.SI technology has imposed a...operating correctly; failed critical real time control applications . n modules are discarded from the vote. the classical "static" voted redundancy...redundant modules are failure number of InterconnecttIon3. This results In f aree. However, for applications requiring higm modular complexity because

  20. Epigenomics and the concept of degeneracy in biological systems

    PubMed Central

    Mason, Paul H.; Barron, Andrew B.

    2014-01-01

    Researchers in the field of epigenomics are developing more nuanced understandings of biological complexity, and exploring the multiple pathways that lead to phenotypic expression. The concept of degeneracy—referring to the multiple pathways that a system recruits to achieve functional plasticity—is an important conceptual accompaniment to the growing body of knowledge in epigenomics. Distinct from degradation, redundancy and dilapidation; degeneracy refers to the plasticity of traits whose function overlaps in some environments, but diverges in others. While a redundant system is composed of repeated identical elements performing the same function, a degenerate system is composed of different elements performing similar or overlapping functions. Here, we describe the degenerate structure of gene regulatory systems from the basic genetic code to flexible epigenomic modifications, and discuss how these structural features have contributed to organism complexity, robustness, plasticity and evolvability. PMID:24335757

  1. Targeting eukaryotic Rab proteins: a smart strategy for chlamydial survival and replication.

    PubMed

    Damiani, María Teresa; Gambarte Tudela, Julián; Capmany, Anahí

    2014-09-01

    Chlamydia, an obligate intracellular bacterium which passes its entire lifecycle within a membrane-bound vacuole called the inclusion, has evolved a variety of unique strategies to establish an advantageous intracellular niche for survival. This review highlights the mechanisms by which Chlamydia subverts vesicular transport in host cells, particularly by hijacking the master controllers of eukaryotic trafficking, the Rab proteins. A subset of Rabs and Rab interacting proteins that control the recycling pathway or the biosynthetic route are selectively recruited to the chlamydial inclusion membrane. By interfering with Rab-controlled transport steps, this intracellular pathogen not only prevents its own degradation in the phagocytic pathway, but also creates a favourable intracellular environment for growth and replication. Chlamydia, a highly adapted and successful intracellular pathogen, has several redundant strategies to re-direct vesicles emerging from biosynthetic compartments that carry host molecules essential for bacterial development. Although current knowledge is limited, the latest findings have shed light on the role of Rab proteins in the course of chlamydial infections and could open novel opportunities for anti-chlamydial therapy. © 2014 John Wiley & Sons Ltd.

  2. Motion control of 7-DOF arms - The configuration control approach

    NASA Technical Reports Server (NTRS)

    Seraji, Homayoun; Long, Mark K.; Lee, Thomas S.

    1993-01-01

    Graphics simulation and real-time implementation of configuration control schemes for a redundant 7-DOF Robotics Research arm are described. The arm kinematics and motion control schemes are described briefly. This is followed by a description of a graphics simulation environment for 7-DOF arm control on the Silicon Graphics IRIS Workstation. Computer simulation results are presented to demonstrate elbow control, collision avoidance, and optimal joint movement as redundancy resolution goals. The laboratory setup for experimental validation of motion control of the 7-DOF Robotics Research arm is then described. The configuration control approach is implemented on a Motorola-68020/VME-bus-based real-time controller, with elbow positioning for redundancy resolution. Experimental results demonstrate the efficacy of configuration control for real-time control.

  3. Endocardial Hippo signaling regulates myocardial growth and cardiogenesis.

    PubMed

    Artap, Stanley; Manderfield, Lauren J; Smith, Cheryl L; Poleshko, Andrey; Aghajanian, Haig; See, Kelvin; Li, Li; Jain, Rajan; Epstein, Jonathan A

    2018-08-01

    The Hippo signaling pathway has been implicated in control of cell and organ size, proliferation, and endothelial-mesenchymal transformation. This pathway impacts upon two partially redundant transcription cofactors, Yap and Taz, that interact with other factors, including members of the Tead family, to affect expression of downstream genes. Yap and Taz have been shown to regulate, in a cell-autonomous manner, myocardial proliferation, myocardial hypertrophy, regenerative potential, and overall size of the heart. Here, we show that Yap and Taz also play an instructive, non-cell-autonomous role in the endocardium of the developing heart to regulate myocardial growth through release of the paracrine factor, neuregulin. Without endocardial Yap and Taz, myocardial growth is impaired causing early post-natal lethality. Thus, the Hippo signaling pathway regulates cell size via both cell-autonomous and non-cell-autonomous mechanisms. Furthermore, these data suggest that Hippo may regulate organ size via a sensing and paracrine function in endothelial cells. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Regulation of autophagy by amino acids and MTOR-dependent signal transduction.

    PubMed

    Meijer, Alfred J; Lorin, Séverine; Blommaart, Edward F; Codogno, Patrice

    2015-10-01

    Amino acids not only participate in intermediary metabolism but also stimulate insulin-mechanistic target of rapamycin (MTOR)-mediated signal transduction which controls the major metabolic pathways. Among these is the pathway of autophagy which takes care of the degradation of long-lived proteins and of the elimination of damaged or functionally redundant organelles. Proper functioning of this process is essential for cell survival. Dysregulation of autophagy has been implicated in the etiology of several pathologies. The history of the studies on the interrelationship between amino acids, MTOR signaling and autophagy is the subject of this review. The mechanisms responsible for the stimulation of MTOR-mediated signaling, and the inhibition of autophagy, by amino acids have been studied intensively in the past but are still not completely clarified. Recent developments in this field are discussed.

  5. A new approach to global control of redundant manipulators

    NASA Technical Reports Server (NTRS)

    Seraji, Homayoun

    1989-01-01

    A new and simple approach to configuration control of redundant manipulators is presented. In this approach, the redundancy is utilized to control the manipulator configuration directly in task space, where the task will be performed. A number of kinematic functions are defined to reflect the desirable configuration that will be achieved for a given end-effector position. The user-defined kinematic functions and the end-effector Cartesian coordinates are combined to form a set of task-related configuration variables as generalized coordinates for the manipulator. An adaptive scheme is then utilized to globally control the configuration variables so as to achieve tracking of some desired reference trajectories. This accomplishes the basic task of desired end-effector motion, while utilizing the redundancy to achieve any additional task through the desired time variation of the kinematic functions. The control law is simple and computationally very fast, and does not require the complex manipulator dynamic model.

  6. Analysis of functional redundancies within the Arabidopsis TCP transcription factor family.

    PubMed

    Danisman, Selahattin; van Dijk, Aalt D J; Bimbo, Andrea; van der Wal, Froukje; Hennig, Lars; de Folter, Stefan; Angenent, Gerco C; Immink, Richard G H

    2013-12-01

    Analyses of the functions of TEOSINTE-LIKE1, CYCLOIDEA, and PROLIFERATING CELL FACTOR1 (TCP) transcription factors have been hampered by functional redundancy between its individual members. In general, putative functionally redundant genes are predicted based on sequence similarity and confirmed by genetic analysis. In the TCP family, however, identification is impeded by relatively low overall sequence similarity. In a search for functionally redundant TCP pairs that control Arabidopsis leaf development, this work performed an integrative bioinformatics analysis, combining protein sequence similarities, gene expression data, and results of pair-wise protein-protein interaction studies for the 24 members of the Arabidopsis TCP transcription factor family. For this, the work completed any lacking gene expression and protein-protein interaction data experimentally and then performed a comprehensive prediction of potential functional redundant TCP pairs. Subsequently, redundant functions could be confirmed for selected predicted TCP pairs by genetic and molecular analyses. It is demonstrated that the previously uncharacterized class I TCP19 gene plays a role in the control of leaf senescence in a redundant fashion with TCP20. Altogether, this work shows the power of combining classical genetic and molecular approaches with bioinformatics predictions to unravel functional redundancies in the TCP transcription factor family.

  7. Analysis of functional redundancies within the Arabidopsis TCP transcription factor family

    PubMed Central

    Danisman, Selahattin; de Folter, Stefan; Immink, Richard G. H.

    2013-01-01

    Analyses of the functions of TEOSINTE-LIKE1, CYCLOIDEA, and PROLIFERATING CELL FACTOR1 (TCP) transcription factors have been hampered by functional redundancy between its individual members. In general, putative functionally redundant genes are predicted based on sequence similarity and confirmed by genetic analysis. In the TCP family, however, identification is impeded by relatively low overall sequence similarity. In a search for functionally redundant TCP pairs that control Arabidopsis leaf development, this work performed an integrative bioinformatics analysis, combining protein sequence similarities, gene expression data, and results of pair-wise protein–protein interaction studies for the 24 members of the Arabidopsis TCP transcription factor family. For this, the work completed any lacking gene expression and protein–protein interaction data experimentally and then performed a comprehensive prediction of potential functional redundant TCP pairs. Subsequently, redundant functions could be confirmed for selected predicted TCP pairs by genetic and molecular analyses. It is demonstrated that the previously uncharacterized class I TCP19 gene plays a role in the control of leaf senescence in a redundant fashion with TCP20. Altogether, this work shows the power of combining classical genetic and molecular approaches with bioinformatics predictions to unravel functional redundancies in the TCP transcription factor family. PMID:24129704

  8. Design structure for in-system redundant array repair in integrated circuits

    DOEpatents

    Bright, Arthur A.; Crumley, Paul G.; Dombrowa, Marc; Douskey, Steven M.; Haring, Rudolf A.; Oakland, Steven F.; Quellette, Michael R.; Strissel, Scott A.

    2008-11-25

    A design structure for repairing an integrated circuit during operation of the integrated circuit. The integrated circuit comprising of a multitude of memory arrays and a fuse box holding control data for controlling redundancy logic of the arrays. The design structure provides the integrated circuit with a control data selector for passing the control data from the fuse box to the memory arrays; providing a source of alternate control data, external of the integrated circuit; and connecting the source of alternate control data to the control data selector. The design structure further passes the alternate control data from the source thereof, through the control data selector and to the memory arrays to control the redundancy logic of the memory arrays.

  9. Intelligent redundant actuation system requirements and preliminary system design

    NASA Technical Reports Server (NTRS)

    Defeo, P.; Geiger, L. J.; Harris, J.

    1985-01-01

    Several redundant actuation system configurations were designed and demonstrated to satisfy the stringent operational requirements of advanced flight control systems. However, this has been accomplished largely through brute force hardware redundancy, resulting in significantly increased computational requirements on the flight control computers which perform the failure analysis and reconfiguration management. Modern technology now provides powerful, low-cost microprocessors which are effective in performing failure isolation and configuration management at the local actuator level. One such concept, called an Intelligent Redundant Actuation System (IRAS), significantly reduces the flight control computer requirements and performs the local tasks more comprehensively than previously feasible. The requirements and preliminary design of an experimental laboratory system capable of demonstrating the concept and sufficiently flexible to explore a variety of configurations are discussed.

  10. Case studies in configuration control for redundant robots

    NASA Technical Reports Server (NTRS)

    Seraji, H.; Lee, T.; Colbaugh, R.; Glass, K.

    1989-01-01

    A simple approach to configuration control of redundant robots is presented. The redundancy is utilized to control the robot configuration directly in task space, where the task will be performed. A number of task-related kinematic functions are defined and combined with the end-effector coordinates to form a set of configuration variables. An adaptive control scheme is then utilized to ensure that the configuration variables track the desired reference trajectories as closely as possible. Simulation results are presented to illustrate the control scheme. The scheme has also been implemented for direct online control of a PUMA industrial robot, and experimental results are presented. The simulation and experimental results validate the configuration control scheme for performing various realistic tasks.

  11. Active parallel redundancy for electronic integrator-type control circuits

    NASA Technical Reports Server (NTRS)

    Peterson, R. A.

    1971-01-01

    Circuit extends concept of redundant feedback control from type-0 to type-1 control systems. Inactive channels are slaves to the active channel, if latter fails, it is rejected and slave channel is activated. High reliability and elimination of single-component catastrophic failure are important in closed-loop control systems.

  12. Morgantown People Mover Redundant Computing System Design Summary

    DOT National Transportation Integrated Search

    1980-09-01

    The purpose of this report is to describe the redundant computing system design used for the current 1980 Phase II Morgantown People Mover (MPM) system. The redundant computing system is that part of the control and communications system (C&CS) consi...

  13. Growth Substrate- and Phase-Specific Expression of Biphenyl, Benzoate, and C1 Metabolic Pathways in Burkholderia xenovorans LB400

    PubMed Central

    Denef, V. J.; Patrauchan, M. A.; Florizone, C.; Park, J.; Tsoi, T. V.; Verstraete, W.; Tiedje, J. M.; Eltis, L. D.

    2005-01-01

    Recent microarray experiments suggested that Burkholderia xenovorans LB400, a potent polychlorinated biphenyl (PCB)-degrading bacterium, utilizes up to three apparently redundant benzoate pathways and a C1 metabolic pathway during biphenyl and benzoate metabolism. To better characterize the roles of these pathways, we performed quantitative proteome profiling of cells grown on succinate, benzoate, or biphenyl and harvested during either mid-logarithmic growth or the transition between the logarithmic and stationary growth phases. The Bph enzymes, catabolizing biphenyl, were ∼16-fold more abundant in biphenyl- versus succinate-grown cells. Moreover, the upper and lower bph pathways were independently regulated. Expression of each benzoate pathway depended on growth substrate and phase. Proteins specifying catabolism via benzoate dihydroxylation and catechol ortho-cleavage (ben-cat pathway) were approximately an order of magnitude more abundant in benzoate- versus biphenyl-grown cells at the same growth phase. The chromosomal copy of the benzoyl-coenzyme A (CoA) (boxC) pathway was also expressed during growth on biphenyl: BoxC proteins were approximately twice as abundant as Ben and Cat proteins under these conditions. By contrast, proteins of the megaplasmid copy of the benzoyl-CoA (boxM) pathway were only detected in transition-phase benzoate-grown cells. Other proteins detected at increased levels in benzoate- and biphenyl-grown cells included general stress response proteins potentially induced by reactive oxygen species formed during aerobic aromatic catabolism. Finally, C1 metabolic enzymes were present in biphenyl-grown cells during transition phase. This study provides insights into the physiological roles and integration of apparently redundant catabolic pathways in large-genome bacteria and establishes a basis for investigating the PCB-degrading abilities of this strain. PMID:16291673

  14. Input relegation control for gross motion of a kinematically redundant manipulator

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

    Unseren, M.A.

    1992-10-01

    This report proposes a method for resolving the kinematic redundancy of a serial link manipulator moving in a three-dimensional workspace. The underspecified problem of solving for the joint velocities based on the classical kinematic velocity model is transformed into a well-specified problem. This is accomplished by augmenting the original model with additional equations which relate a new vector variable quantifying the redundant degrees of freedom (DOF) to the joint velocities. The resulting augmented system yields a well specified solution for the joint velocities. Methods for selecting the redundant DOF quantifying variable and the transformation matrix relating it to the jointmore » velocities are presented so as to obtain a minimum Euclidean norm solution for the joint velocities. The approach is also applied to the problem of resolving the kinematic redundancy at the acceleration level. Upon resolving the kinematic redundancy, a rigid body dynamical model governing the gross motion of the manipulator is derived. A control architecture is suggested which according to the model, decouples the Cartesian space DOF and the redundant DOF.« less

  15. Detumbling control for kinematically redundant space manipulator post-grasping a rotational satellite

    NASA Astrophysics Data System (ADS)

    Wang, Mingming; Luo, Jianjun; Yuan, Jianping; Walter, Ulrich

    2017-12-01

    The objective of this paper is to establish a detumbling strategy and a coordination control scheme for a kinematically redundant space manipulator post-grasping a rotational satellite. First, the dynamics of the kinematically redundant space robot after grasping the target is presented, which lays the foundation for the coordination controller design. Subsequently, optimal detumbling and motion planning strategy for the post-capture phase is proposed based on the quartic Bézier curves and adaptive differential evolution (DE) algorithm subject to the specific constraints. Both detumbling time and control torques are taken into account for the generation of the optimal detumbling strategy. Furthermore, a coordination control scheme is presented to track the designed reference path while regulating the attitude of the chaser to a desired value, which successfully dumps the initial angular velocity of the rotational satellite and controls the base attitude synchronously. Simulation results are presented for detumbling a target with rotational motion using a 7 degree-of-freedom (DOF) redundant space manipulator, which demonstrates the effectiveness of the proposed method.

  16. Targeting MUC1 mediated tumor stromal metabolic interaction in Triple negative Breast Cancer

    DTIC Science & Technology

    2016-11-01

    biosynthesis, D- Glutamine and D-glutamate metabolism, Nicotinate and nicotinamide metabolism, and Nitrogen metabolism were amongst the redundant...pathways identified in MDA- MB-468 (Fig 3). Nitrogen metabolism and D- Glutamine and D-glutamate metabolism pathways were filtered out as potential...Figure 4. MUC1 alters TNBC metabolism. Representation of (A) D- Glutamine and D- glutamate metabolism and (B

  17. Targeting MUC1-Mediated Tumor-Stromal Metabolic Interaction in Triple-Negative Breast Cancer

    DTIC Science & Technology

    2016-11-01

    biosynthesis, D- Glutamine and D-glutamate metabolism, Nicotinate and nicotinamide metabolism, and Nitrogen metabolism were amongst the redundant...pathways identified in MDA- MB-468 (Fig 3). Nitrogen metabolism and D- Glutamine and D-glutamate metabolism pathways were filtered out as potential...Figure 4. MUC1 alters TNBC metabolism. Representation of (A) D- Glutamine and D- glutamate metabolism and (B

  18. Kinematically redundant robot manipulators

    NASA Technical Reports Server (NTRS)

    Baillieul, J.; Hollerbach, J.; Brockett, R.; Martin, D.; Percy, R.; Thomas, R.

    1987-01-01

    Research on control, design and programming of kinematically redundant robot manipulators (KRRM) is discussed. These are devices in which there are more joint space degrees of freedom than are required to achieve every position and orientation of the end-effector necessary for a given task in a given workspace. The technological developments described here deal with: kinematic programming techniques for automatically generating joint-space trajectories to execute prescribed tasks; control of redundant manipulators to optimize dynamic criteria (e.g., applications of forces and moments at the end-effector that optimally distribute the loading of actuators); and design of KRRMs to optimize functionality in congested work environments or to achieve other goals unattainable with non-redundant manipulators. Kinematic programming techniques are discussed, which show that some pseudo-inverse techniques that have been proposed for redundant manipulator control fail to achieve the goals of avoiding kinematic singularities and also generating closed joint-space paths corresponding to close paths of the end effector in the workspace. The extended Jacobian is proposed as an alternative to pseudo-inverse techniques.

  19. Redundant function of DNA ligase 1 and 3 in alternative end-joining during immunoglobulin class switch recombination.

    PubMed

    Masani, Shahnaz; Han, Li; Meek, Katheryn; Yu, Kefei

    2016-02-02

    Nonhomologous end-joining (NHEJ) is the major DNA double-strand break (DSB) repair pathway in mammals and resolves the DSBs generated during both V(D)J recombination in developing lymphocytes and class switch recombination (CSR) in antigen-stimulated B cells. In contrast to the absolute requirement for NHEJ to resolve DSBs associated with V(D)J recombination, DSBs associated with CSR can be resolved in NHEJ-deficient cells (albeit at a reduced level) by a poorly defined alternative end-joining (A-EJ) pathway. Deletion of DNA ligase IV (Lig4), a core component of the NHEJ pathway, reduces CSR efficiency in a mouse B-cell line capable of robust cytokine-stimulated CSR in cell culture. Here, we report that CSR levels are not further reduced by deletion of either of the two remaining DNA ligases (Lig1 and nuclear Lig3) in Lig4(-/-) cells. We conclude that in the absence of Lig4, Lig1, and Lig3 function in a redundant manner in resolving switch region DSBs during CSR.

  20. Kinematic control of redundant robots and the motion optimizability measure.

    PubMed

    Li, L; Gruver, W A; Zhang, Q; Yang, Z

    2001-01-01

    This paper treats the kinematic control of manipulators with redundant degrees of freedom. We derive an analytical solution for the inverse kinematics that provides a means for accommodating joint velocity constraints in real time. We define the motion optimizability measure and use it to develop an efficient method for the optimization of joint trajectories subject to multiple criteria. An implementation of the method for a 7-dof experimental redundant robot is present.

  1. Method and apparatus for in-system redundant array repair on integrated circuits

    DOEpatents

    Bright, Arthur A [Croton-on-Hudson, NY; Crumley, Paul G [Yorktown Heights, NY; Dombrowa, Marc B [Bronx, NY; Douskey, Steven M [Rochester, MN; Haring, Rudolf A [Cortlandt Manor, NY; Oakland, Steven F [Colchester, VT; Ouellette, Michael R [Westford, VT; Strissel, Scott A [Byron, MN

    2008-07-29

    Disclosed is a method of repairing an integrated circuit of the type comprising of a multitude of memory arrays and a fuse box holding control data for controlling redundancy logic of the arrays. The method comprises the steps of providing the integrated circuit with a control data selector for passing the control data from the fuse box to the memory arrays; providing a source of alternate control data, external of the integrated circuit; and connecting the source of alternate control data to the control data selector. The method comprises the further step of, at a given time, passing the alternate control data from the source thereof, through the control data selector and to the memory arrays to control the redundancy logic of the memory arrays.

  2. Method and apparatus for in-system redundant array repair on integrated circuits

    DOEpatents

    Bright, Arthur A [Croton-on-Hudson, NY; Crumley, Paul G [Yorktown Heights, NY; Dombrowa, Marc B [Bronx, NY; Douskey, Steven M [Rochester, MN; Haring, Rudolf A [Cortlandt Manor, NY; Oakland, Steven F [Colchester, VT; Ouellette, Michael R [Westford, VT; Strissel, Scott A [Byron, MN

    2008-07-08

    Disclosed is a method of repairing an integrated circuit of the type comprising of a multitude of memory arrays and a fuse box holding control data for controlling redundancy logic of the arrays. The method comprises the steps of providing the integrated circuit with a control data selector for passing the control data from the fuse box to the memory arrays; providing a source of alternate control data, external of the integrated circuit; and connecting the source of alternate control data to the control data selector. The method comprises the further step of, at a given time, passing the alternate control data from the source thereof, through the control data selector and to the memory arrays to control the redundancy logic of the memory arrays.

  3. Method and apparatus for in-system redundant array repair on integrated circuits

    DOEpatents

    Bright, Arthur A.; Crumley, Paul G.; Dombrowa, Marc B.; Douskey, Steven M.; Haring, Rudolf A.; Oakland, Steven F.; Ouellette, Michael R.; Strissel, Scott A.

    2007-12-18

    Disclosed is a method of repairing an integrated circuit of the type comprising of a multitude of memory arrays and a fuse box holding control data for controlling redundancy logic of the arrays. The method comprises the steps of providing the integrated circuit with a control data selector for passing the control data from the fuse box to the memory arrays; providing a source of alternate control data, external of the integrated circuit; and connecting the source of alternate control data to the control data selector. The method comprises the further step of, at a given time, passing the alternate control data from the source thereof, through the control data selector and to the memory arrays to control the redundancy logic of the memory arrays.

  4. 126. REDUNDANCY SYSTEM CONTROLS FOR UMBILICAL MAST RETRACTION AT LOWER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    126. REDUNDANCY SYSTEM CONTROLS FOR UMBILICAL MAST RETRACTION AT LOWER LEFT SIDE OF HYDRAULIC CONTROL PANEL IN UMBILICAL MAST PUMP ROOM (209), LSB (BLDG. 751) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  5. 109. REDUNDANCY SYSTEM CONTROLS FOR UMBILICAL MAST RETRACTION AT LOWER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    109. REDUNDANCY SYSTEM CONTROLS FOR UMBILICAL MAST RETRACTION AT LOWER LEFT SIDE OF HYDRAULIC CONTROL PANEL IN UMBILICAL MAST PUMP ROOM (109), LSB (BLDG. 770) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  6. Viruses Associated with Human Cancer

    PubMed Central

    McLaughlin-Drubin, Margaret E.; Munger, Karl

    2008-01-01

    It is estimated that viral infections contribute to 15–20% of all human cancers. As obligatory intracellular parasites, viruses encode proteins that reprogram host cellular signaling pathways that control proliferation, differentiation, cell death, genomic integrity, and recognition by the immune system. These cellular processes are governed by complex and redundant regulatory networks and are surveyed by sentinel mechanisms that ensure that aberrant cells are removed from the proliferative pool. Given that the genome size of a virus is highly restricted to ensure packaging within an infectious structure, viruses must target cellular regulatory nodes with limited redundancy and need to inactivate surveillance mechanisms that would normally recognize and extinguish such abnormal cells. In many cases, key proteins in these same regulatory networks are subject to mutation in non-virally associated diseases and cancers. Oncogenic viruses have thus served as important experimental models to identify and molecularly investigate such cellular networks. These include the discovery of oncogenes and tumor suppressors, identification of regulatory networks that are critical for maintenance of genomic integrity, and processes that govern immune surveillance. PMID:18201576

  7. The golgin GMAP-210 is required for efficient membrane trafficking in the early secretory pathway

    PubMed Central

    Roboti, Peristera; Sato, Keisuke; Lowe, Martin

    2015-01-01

    Golgins are coiled-coil proteins that participate in membrane-tethering events at the Golgi complex. Golgin-mediated tethering is thought to be important for vesicular trafficking and Golgi organization. However, the degree to which individual golgins contribute to these processes is poorly defined, and it has been proposed that golgins act in a largely redundant manner. Previous studies on the golgin GMAP-210 (also known as TRIP11), which is mutated in the rare skeletal disorder achondrogenesis type 1A, have yielded conflicting results regarding its involvement in trafficking. Here, we re-investigated the trafficking role of GMAP-210, and found that it is indeed required for efficient trafficking in the secretory pathway. GMAP-210 acts at both the endoplasmic reticulum (ER)-to-Golgi intermediate compartment (ERGIC) and Golgi complex during anterograde trafficking, and is also required for retrograde trafficking to the ER. Using co-depletion experiments, we also found that GMAP-210 acts in a partially redundant manner with the golgin GM130 to ensure efficient anterograde cargo delivery to the cis-Golgi. In summary, our results indicate a role for GMAP-210 in several trafficking steps at the ER–Golgi interface, some of which are partially redundant with another golgin, namely GM130 (also known as GOLGA2). PMID:25717001

  8. Kinematically redundant arm formulations for coordinated multiple arm implementations

    NASA Technical Reports Server (NTRS)

    Bailey, Robert W.; Quiocho, Leslie J.; Cleghorn, Timothy F.

    1990-01-01

    Although control laws for kinematically redundant robotic arms were presented as early as 1969, redundant arms have only recently become recognized as viable solutions to limitations inherent to kinematically sufficient arms. The advantages of run-time control optimization and arm reconfiguration are becoming increasingly attractive as the complexity and criticality of robotic systems continues to progress. A generalized control law for a spatial arm with 7 or more degrees of freedom (DOF) based on Whitney's resolved rate formulation is given. Results from a simulation implementation utilizing this control law are presented. Furthermore, results from a two arm simulation are presented to demonstrate the coordinated control of multiple arms using this formulation.

  9. Reconfiguring redundancy management

    NASA Technical Reports Server (NTRS)

    Gelderloos, H. J. C. (Inventor)

    1982-01-01

    A redundancy management system is described wherein input signals from a sensor are provided redundantly in parallel so that a primary control signal may be selected. Median value signals for groups of three sensors are detected in median value selectors of selection filter. The detected median value signals are then also compared in a subtractor/comparator to determine whether any of them exceed the others by an amount greater than the signal level for a failed sensor. If so, the exceeding detected medium value signal is sent to a control computer as the primary control signal. If not, the lowest level detected medium value signal is sent as the primary control signal.

  10. New Algorithms Manage Fourfold Redundancy

    NASA Technical Reports Server (NTRS)

    Gelderloos, H. C.

    1982-01-01

    Redundant sensors, actuators, and computers improve reliability of complex control systems, such as those in nuclear powerplants and aircraft. If one or more redundant elements fail, another takes over so that normal operation is not interrupted. Quad selection filter rejects data from null-failed and hardover-failed and hardover-failed units.

  11. Spatial Map of Synthesized Criteria for the Redundancy Resolution of Human Arm Movements.

    PubMed

    Li, Zhi; Milutinovic, Dejan; Rosen, Jacob

    2015-11-01

    The kinematic redundancy of the human arm enables the elbow position to rotate about the axis going through the shoulder and wrist, which results in infinite possible arm postures when the arm reaches to a target in a 3-D workspace. To infer the control strategy the human motor system uses to resolve redundancy in reaching movements, this paper compares five redundancy resolution criteria and evaluates their arm posture prediction performance using data on healthy human motion. Two synthesized criteria are developed to provide better real-time arm posture prediction than the five individual criteria. Of these two, the criterion synthesized using an exponential method predicts the arm posture more accurately than that using a least squares approach, and therefore is preferable for inferring the contributions of the individual criteria to motor control during reaching movements. As a methodology contribution, this paper proposes a framework to compare and evaluate redundancy resolution criteria for arm motion control. A cluster analysis which associates criterion contributions with regions of the workspace provides a guideline for designing a real-time motion control system applicable to upper-limb exoskeletons for stroke rehabilitation.

  12. In-flight performance optimization for rotorcraft with redundant controls

    NASA Astrophysics Data System (ADS)

    Ozdemir, Gurbuz Taha

    A conventional helicopter has limits on performance at high speeds because of the limitations of main rotor, such as compressibility issues on advancing side or stall issues on retreating side. Auxiliary lift and thrust components have been suggested to improve performance of the helicopter substantially by reducing the loading on the main rotor. Such a configuration is called the compound rotorcraft. Rotor speed can also be varied to improve helicopter performance. In addition to improved performance, compound rotorcraft and variable RPM can provide a much larger degree of control redundancy. This additional redundancy gives the opportunity to further enhance performance and handling qualities. A flight control system is designed to perform in-flight optimization of redundant control effectors on a compound rotorcraft in order to minimize power required and extend range. This "Fly to Optimal" (FTO) control law is tested in simulation using the GENHEL model. A model of the UH-60, a compound version of the UH-60A with lifting wing and vectored thrust ducted propeller (VTDP), and a generic compound version of the UH-60A with lifting wing and propeller were developed and tested in simulation. A model following dynamic inversion controller is implemented for inner loop control of roll, pitch, yaw, heave, and rotor RPM. An outer loop controller regulates airspeed and flight path during optimization. A Golden Section search method was used to find optimal rotor RPM on a conventional helicopter, where the single redundant control effector is rotor RPM. The FTO builds off of the Adaptive Performance Optimization (APO) method of Gilyard by performing low frequency sweeps on a redundant control for a fixed wing aircraft. A method based on the APO method was used to optimize trim on a compound rotorcraft with several redundant control effectors. The controller can be used to optimize rotor RPM and compound control effectors through flight test or simulations in order to establish a schedule. The method has been expanded to search a two-dimensional control space. Simulation results demonstrate the ability to maximize range by optimizing stabilator deflection and an airspeed set point. Another set of results minimize power required in high speed flight by optimizing collective pitch and stabilator deflection. Results show that the control laws effectively hold the flight condition while the FTO method is effective at improving performance. Optimizations show there can be issues when the control laws regulating altitude push the collective control towards it limits. So a modification was made to the control law to regulate airspeed and altitude using propeller pitch and angle of attack while the collective is held fixed or used as an optimization variable. A dynamic trim limit avoidance algorithm is applied to avoid control saturation in other axes during optimization maneuvers. Range and power optimization FTO simulations are compared with comprehensive sweeps of trim solutions and FTO optimization shown to be effective and reliable in reaching an optimal when optimizing up to two redundant controls. Use of redundant controls is shown to be beneficial for improving performance. The search method takes almost 25 minutes of simulated flight for optimization to be complete. The optimization maneuver itself can sometimes drive the power required to high values, so a power limit is imposed to restrict the search to avoid conditions where power is more than5% higher than that of the initial trim state. With this modification, the time the optimization maneuver takes to complete is reduced down to 21 minutes without any significant change in the optimal power value.

  13. Distributed and recoverable digital control system

    NASA Technical Reports Server (NTRS)

    Stange, Kent (Inventor); Hess, Richard (Inventor); Kelley, Gerald B (Inventor); Rogers, Randy (Inventor)

    2010-01-01

    A real-time multi-tasking digital control system with rapid recovery capability is disclosed. The control system includes a plurality of computing units comprising a plurality of redundant processing units, with each of the processing units configured to generate one or more redundant control commands. One or more internal monitors are employed for detecting data errors in the control commands. One or more recovery triggers are provided for initiating rapid recovery of a processing unit if data errors are detected. The control system also includes a plurality of actuator control units each in operative communication with the computing units. The actuator control units are configured to initiate a rapid recovery if data errors are detected in one or more of the processing units. A plurality of smart actuators communicates with the actuator control units, and a plurality of redundant sensors communicates with the computing units.

  14. Autonomous control system reconfiguration for spacecraft with non-redundant actuators

    NASA Astrophysics Data System (ADS)

    Grossman, Walter

    1995-05-01

    The Small Satellite Technology Initiative (SSTI) 'CLARK' spacecraft is required to be single-failure tolerant, i.e., no failure of any single component or subsystem shall result in complete mission loss. Fault tolerance is usually achieved by implementing redundant subsystems. Fault tolerant systems are therefore heavier and cost more to build and launch than non-redundent, non fault-tolerant spacecraft. The SSTI CLARK satellite Attitude Determination and Control System (ADACS) achieves single-fault tolerance without redundancy. The attitude determination system system uses a Kalman Filter which is inherently robust to loss of any single attitude sensor. The attitude control system uses three orthogonal reaction wheels for attitude control and three magnetic dipoles for momentum control. The nominal six-actuator control system functions by projecting the attitude correction torque onto the reaction wheels while a slower momentum management outer loop removes the excess momentum in the direction normal to the local B field. The actuators are not redundant so the nominal control law cannot be implemented in the event of a loss of a single actuator (dipole or reaction wheel). The spacecraft dynamical state (attitude, angular rate, and momentum) is controllable from any five-element subset of the six actuators. With loss of an actuator the instantaneous control authority may not span R(3) but the controllability gramian integral(limits between t,0) Phi(t, tau)B(tau )B(prime)(tau) Phi(prime)(t, tau)d tau retains full rank. Upon detection of an actuator failure the control torque is decomposed onto the remaining active axes. The attitude control torque is effected and the over-orbit momentum is controlled. The resulting control system performance approaches that of the nominal system.

  15. Finite-Horizon $H_\\infty $ Consensus for Multiagent Systems With Redundant Channels via An Observer-Type Event-Triggered Scheme.

    PubMed

    Xu, Wenying; Wang, Zidong; Ho, Daniel W C

    2018-05-01

    This paper is concerned with the finite-horizon consensus problem for a class of discrete time-varying multiagent systems with external disturbances and missing measurements. To improve the communication reliability, redundant channels are introduced and the corresponding protocol is constructed for the information transmission over redundant channels. An event-triggered scheme is adopted to determine whether the information of agents should be transmitted to their neighbors. Subsequently, an observer-type event-triggered control protocol is proposed based on the latest received neighbors' information. The purpose of the addressed problem is to design a time-varying controller based on the observed information to achieve the consensus performance in a finite horizon. By utilizing a constrained recursive Riccati difference equation approach, some sufficient conditions are obtained to guarantee the consensus performance, and the controller parameters are also designed. Finally, a numerical example is provided to demonstrate the desired reliability of redundant channels and the effectiveness of the event-triggered control protocol.

  16. HSF-1 activates the ubiquitin proteasome system to promote non-apoptotic developmental cell death in C. elegans.

    PubMed

    Kinet, Maxime J; Malin, Jennifer A; Abraham, Mary C; Blum, Elyse S; Silverman, Melanie R; Lu, Yun; Shaham, Shai

    2016-03-08

    Apoptosis is a prominent metazoan cell death form. Yet, mutations in apoptosis regulators cause only minor defects in vertebrate development, suggesting that another developmental cell death mechanism exists. While some non-apoptotic programs have been molecularly characterized, none appear to control developmental cell culling. Linker-cell-type death (LCD) is a morphologically conserved non-apoptotic cell death process operating in Caenorhabditis elegans and vertebrate development, and is therefore a compelling candidate process complementing apoptosis. However, the details of LCD execution are not known. Here we delineate a molecular-genetic pathway governing LCD in C. elegans. Redundant activities of antagonistic Wnt signals, a temporal control pathway, and mitogen-activated protein kinase kinase signaling control heat shock factor 1 (HSF-1), a conserved stress-activated transcription factor. Rather than protecting cells, HSF-1 promotes their demise by activating components of the ubiquitin proteasome system, including the E2 ligase LET-70/UBE2D2 functioning with E3 components CUL-3, RBX-1, BTBD-2, and SIAH-1. Our studies uncover design similarities between LCD and developmental apoptosis, and provide testable predictions for analyzing LCD in vertebrates.

  17. DELAY OF GERMINATION1 requires PP2C phosphatases of the ABA signalling pathway to control seed dormancy.

    PubMed

    Née, Guillaume; Kramer, Katharina; Nakabayashi, Kazumi; Yuan, Bingjian; Xiang, Yong; Miatton, Emma; Finkemeier, Iris; Soppe, Wim J J

    2017-07-13

    The time of seed germination is a major decision point in the life of plants determining future growth and development. This timing is controlled by seed dormancy, which prevents germination under favourable conditions. The plant hormone abscisic acid (ABA) and the protein DELAY OF GERMINATION 1 (DOG1) are essential regulators of dormancy. The function of ABA in dormancy is rather well understood, but the role of DOG1 is still unknown. Here, we describe four phosphatases that interact with DOG1 in seeds. Two of them belong to clade A of type 2C protein phosphatases: ABA-HYPERSENSITIVE GERMINATION 1 (AHG1) and AHG3. These phosphatases have redundant but essential roles in the release of seed dormancy epistatic to DOG1. We propose that the ABA and DOG1 dormancy pathways converge at clade A of type 2C protein phosphatases.The DOG1 protein is a major regulator of seed dormancy in Arabidopsis. Here, Née et al. provide evidence that DOG1 can interact with the type 2C protein phosphatases AHG1 and AHG3 and that this represents the convergence point of the DOG1-regulated dormancy pathway and signalling by the plant hormone abscisic acid.

  18. Exploration of joint redundancy but not task space variability facilitates supervised motor learning.

    PubMed

    Singh, Puneet; Jana, Sumitash; Ghosal, Ashitava; Murthy, Aditya

    2016-12-13

    The number of joints and muscles in a human arm is more than what is required for reaching to a desired point in 3D space. Although previous studies have emphasized how such redundancy and the associated flexibility may play an important role in path planning, control of noise, and optimization of motion, whether and how redundancy might promote motor learning has not been investigated. In this work, we quantify redundancy space and investigate its significance and effect on motor learning. We propose that a larger redundancy space leads to faster learning across subjects. We observed this pattern in subjects learning novel kinematics (visuomotor adaptation) and dynamics (force-field adaptation). Interestingly, we also observed differences in the redundancy space between the dominant hand and nondominant hand that explained differences in the learning of dynamics. Taken together, these results provide support for the hypothesis that redundancy aids in motor learning and that the redundant component of motor variability is not noise.

  19. Exploration of joint redundancy but not task space variability facilitates supervised motor learning

    PubMed Central

    Singh, Puneet; Jana, Sumitash; Ghosal, Ashitava; Murthy, Aditya

    2016-01-01

    The number of joints and muscles in a human arm is more than what is required for reaching to a desired point in 3D space. Although previous studies have emphasized how such redundancy and the associated flexibility may play an important role in path planning, control of noise, and optimization of motion, whether and how redundancy might promote motor learning has not been investigated. In this work, we quantify redundancy space and investigate its significance and effect on motor learning. We propose that a larger redundancy space leads to faster learning across subjects. We observed this pattern in subjects learning novel kinematics (visuomotor adaptation) and dynamics (force-field adaptation). Interestingly, we also observed differences in the redundancy space between the dominant hand and nondominant hand that explained differences in the learning of dynamics. Taken together, these results provide support for the hypothesis that redundancy aids in motor learning and that the redundant component of motor variability is not noise. PMID:27911808

  20. Singularity-robustness and task-prioritization in configuration control of redundant robots

    NASA Technical Reports Server (NTRS)

    Seraji, H.; Colbaugh, R.

    1990-01-01

    The authors present a singularity-robust task-prioritized reformulation of the configuration control for redundant robot manipulators. This reformation suppresses large joint velocities to induce minimal errors in the task performance by modifying the task trajectories. Furthermore, the same framework provides a means for assignment of priorities between the basic task of end-effector motion and the user-defined additional task for utilizing redundancy. This allows automatic relaxation of the additional task constraints in favor of the desired end-effector motion when both cannot be achieved exactly.

  1. Evidence for the retention of two evolutionary distinct plastids in dinoflagellates with diatom endosymbionts.

    PubMed

    Hehenberger, Elisabeth; Imanian, Behzad; Burki, Fabien; Keeling, Patrick J

    2014-09-01

    Dinoflagellates harboring diatom endosymbionts (termed "dinotoms") have undergone a process often referred to as "tertiary endosymbiosis"--the uptake of algae containing secondary plastids and integration of those plastids into the new host. In contrast to other tertiary plastids, and most secondary plastids, the endosymbiont of dinotoms is distinctly less reduced, retaining a number of cellular features, such as their nucleus and mitochondria and others, in addition to their plastid. This has resulted in redundancy between host and endosymbiont, at least between some mitochondrial and cytosolic metabolism, where this has been investigated. The question of plastidial redundancy is particularly interesting as the fate of the host dinoflagellate plastid is unclear. The host cytosol possesses an eyespot that has been postulated to be a remnant of the ancestral peridinin plastid, but this has not been tested, nor has its possible retention of plastid functions. To investigate this possibility, we searched for plastid-associated pathways and functions in transcriptomic data sets from three dinotom species. We show that the dinoflagellate host has indeed retained genes for plastid-associated pathways and that these genes encode targeting peptides similar to those of other dinoflagellate plastid-targeted proteins. Moreover, we also identified one gene encoding an essential component of the dinoflagellate plastid protein import machinery, altogether suggesting the presence of a functioning plastid import system in the host, and by extension a relict plastid. The presence of the same plastid-associated pathways in the endosymbiont also extends the known functional redundancy in dinotoms, further confirming the unusual state of plastid integration in this group of dinoflagellates. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  2. Controlling Split Attention and Redundancy in Physical Therapy Instruction

    ERIC Educational Resources Information Center

    Pociask, Fredrick D.; Morrison, Gary R.

    2008-01-01

    In this study, we examined the effectiveness of instructional materials designed to control redundancy and split attention in the teaching of complex orthopedic physical therapy skills. Participants included 41 first-year physical therapy students. The modified instruction group received a modified unit of instruction designed to reduce cognitive…

  3. A Core Regulatory Pathway Controlling Rice Tiller Angle Mediated by the LAZY1-dependent Asymmetric Distribution of Auxin.

    PubMed

    Zhang, Ning; Yu, Hong; Yu, Hao; Cai, Yueyue; Huang, Linzhou; Xu, Cao; Xiong, Guosheng; Meng, Xiangbing; Wang, Jiyao; Chen, Haofeng; Liu, Guifu; Jing, Yanhui; Yuan, Yundong; Liang, Yan; Li, Shujia; Smith, Steven M; Li, Jiayang; Wang, Yonghong

    2018-06-18

    Tiller angle in cereals is a key shoot architecture trait that strongly influences grain yield. Studies in rice (Oryza sativa L.) have implicated shoot gravitropism in the regulation of tiller angle. However, the functional link between shoot gravitropism and tiller angle is unknown. Here, we conducted a large-scale transcriptome analysis of rice shoots in response to gravistimulation and identified two new nodes of a shoot gravitropism regulatory gene network that also controls rice tiller angle. We demonstrate that HEAT STRESS TRANSCRIPTION FACTOR 2D (HSFA2D) is an upstream positive regulator of the LAZY1-mediated asymmetric auxin distribution pathway. We also show that two functionally redundant transcription factor genes, WUSCHEL RELATED HOMEOBOX6 (WOX6) and WOX11, are expressed asymmetrically in response to auxin to connect gravitropism responses with the control of rice tiller angle. These findings define upstream and downstream genetic components that link shoot gravitropism, asymmetric auxin distribution, and rice tiller angle. The results highlight the power of the high-temporal-resolution RNA-seq dataset, and its use to explore further genetic components controlling tiller angle. Collectively these approaches will identify genes to improve grain yields by facilitating the optimization of plant architecture. © 2018 American Society of Plant Biologists. All rights reserved.

  4. Reliable dual-redundant sensor failure detection and identification for the NASA F-8 DFBW aircraft

    NASA Technical Reports Server (NTRS)

    Deckert, J. C.; Desai, M. N.; Deyst, J. J., Jr.; Willsky, A. S.

    1978-01-01

    A technique was developed which provides reliable failure detection and identification (FDI) for a dual redundant subset of the flight control sensors onboard the NASA F-8 digital fly by wire (DFBW) aircraft. The technique was successfully applied to simulated sensor failures on the real time F-8 digital simulator and to sensor failures injected on telemetry data from a test flight of the F-8 DFBW aircraft. For failure identification the technique utilized the analytic redundancy which exists as functional and kinematic relationships among the various quantities being measured by the different control sensor types. The technique can be used not only in a dual redundant sensor system, but also in a more highly redundant system after FDI by conventional voting techniques reduced to two the number of unfailed sensors of a particular type. In addition the technique can be easily extended to the case in which only one sensor of a particular type is available.

  5. Symmetry breaking and polarization of the C. elegans zygote by the polarity protein PAR-2.

    PubMed

    Zonies, Seth; Motegi, Fumio; Hao, Yingsong; Seydoux, Geraldine

    2010-05-01

    Polarization of the C. elegans zygote is initiated by ECT-2-dependent cortical flows, which mobilize the anterior PAR proteins (PAR-3, PAR-6 and PKC-3) away from the future posterior end of the embryo marked by the sperm centrosome. Here, we demonstrate the existence of a second, parallel and redundant pathway that can polarize the zygote in the absence of ECT-2-dependent cortical flows. This second pathway depends on the polarity protein PAR-2. We show that PAR-2 localizes to the cortex nearest the sperm centrosome even in the absence of cortical flows. Once on the cortex, PAR-2 antagonizes PAR-3-dependent recruitment of myosin, creating myosin flows that transport the anterior PAR complex away from PAR-2 in a positive-feedback loop. We propose that polarity in the C. elegans zygote is initiated by redundant ECT-2- and PAR-2-dependent mechanisms that lower PAR-3 levels locally, triggering a positive-feedback loop that polarizes the entire cortex.

  6. Redundancy and modularity in membrane-associated dissimilatory nitrate reduction in Bacillus

    PubMed Central

    Heylen, Kim; Keltjens, Jan

    2012-01-01

    The genomes of two phenotypically denitrifying type strains of the genus Bacillus were sequenced and the pathways for dissimilatory nitrate reduction were reconstructed. Results suggest that denitrification proceeds in the periplasmic space and in an analogous fashion as in Gram-negative organisms, yet with the participation of proteins that tend to be membrane-bound or membrane-associated. A considerable degree of functional redundancy was observed with marked differences between B. azotoformans LMG 9581T and B. bataviensis LMG 21833T. In addition to the already characterized menaquinol/cyt c-dependent nitric oxide reductase (Suharti et al., 2001, 2004) of which the encoding genes could be identified now, evidence for another novel nitric oxide reductase (NOR) was found. Also, our analyses confirm earlier findings on branched electron transfer with both menaquinol and cytochrome c as reductants. Quite unexpectedly, both bacilli have the disposal of two parallel pathways for nitrite reduction enabling a life style as a denitrifier and as an ammonifying bacterium. PMID:23087684

  7. Deciphering a unique biotin scavenging pathway with redundant genes in the probiotic bacterium Lactococcus lactis

    PubMed Central

    Zhang, Huimin; Wang, Qingjing; Fisher, Derek J.; Cai, Mingzhu; Chakravartty, Vandana; Ye, Huiyan; Li, Ping; Solbiati, Jose O.; Feng, Youjun

    2016-01-01

    Biotin protein ligase (BPL) is widespread in the three domains of the life. The paradigm BPL is the Escherichia coli BirA protein, which also functions as a repressor for the biotin biosynthesis pathway. Here we report that Lactococcus lactis possesses two different orthologues of birA (birA1_LL and birA2_LL). Unlike the scenario in E. coli, L. lactis appears to be auxotrophic for biotin in that it lacks a full biotin biosynthesis pathway. In contrast, it retains two biotin transporter-encoding genes (bioY1_LL and bioY2_LL), suggesting the use of a scavenging strategy to obtain biotin from the environment. The in vivo function of the two L. lactis birA genes was judged by their abilities to complement the conditional lethal E. coli birA mutant. Thin-layer chromatography and mass spectroscopy assays demonstrated that these two recombinant BirA proteins catalyze the biotinylation reaction of the acceptor biotin carboxyl carrier protein (BCCP), through the expected biotinoyl-AMP intermediate. Gel shift assays were used to characterize bioY1_LL and BirA1_LL. We also determined the ability to uptake 3H-biotin by L. lactis. Taken together, our results deciphered a unique biotin scavenging pathway with redundant genes present in the probiotic bacterium L. lactis. PMID:27161258

  8. Deciphering a unique biotin scavenging pathway with redundant genes in the probiotic bacterium Lactococcus lactis.

    PubMed

    Zhang, Huimin; Wang, Qingjing; Fisher, Derek J; Cai, Mingzhu; Chakravartty, Vandana; Ye, Huiyan; Li, Ping; Solbiati, Jose O; Feng, Youjun

    2016-05-10

    Biotin protein ligase (BPL) is widespread in the three domains of the life. The paradigm BPL is the Escherichia coli BirA protein, which also functions as a repressor for the biotin biosynthesis pathway. Here we report that Lactococcus lactis possesses two different orthologues of birA (birA1_LL and birA2_LL). Unlike the scenario in E. coli, L. lactis appears to be auxotrophic for biotin in that it lacks a full biotin biosynthesis pathway. In contrast, it retains two biotin transporter-encoding genes (bioY1_LL and bioY2_LL), suggesting the use of a scavenging strategy to obtain biotin from the environment. The in vivo function of the two L. lactis birA genes was judged by their abilities to complement the conditional lethal E. coli birA mutant. Thin-layer chromatography and mass spectroscopy assays demonstrated that these two recombinant BirA proteins catalyze the biotinylation reaction of the acceptor biotin carboxyl carrier protein (BCCP), through the expected biotinoyl-AMP intermediate. Gel shift assays were used to characterize bioY1_LL and BirA1_LL. We also determined the ability to uptake (3)H-biotin by L. lactis. Taken together, our results deciphered a unique biotin scavenging pathway with redundant genes present in the probiotic bacterium L. lactis.

  9. Sensor failure detection for jet engines

    NASA Technical Reports Server (NTRS)

    Merrill, Walter C.

    1988-01-01

    The use of analytical redundancy to improve gas turbine engine control system reliability through sensor failure detection, isolation, and accommodation is surveyed. Both the theoretical and application papers that form the technology base of turbine engine analytical redundancy research are discussed. Also, several important application efforts are reviewed. An assessment of the state-of-the-art in analytical redundancy technology is given.

  10. Fallback options for airgap sensor fault of an electromagnetic suspension system

    NASA Astrophysics Data System (ADS)

    Michail, Konstantinos; Zolotas, Argyrios C.; Goodall, Roger M.

    2013-06-01

    The paper presents a method to recover the performance of an electromagnetic suspension under faulty airgap sensor. The proposed control scheme is a combination of classical control loops, a Kalman Estimator and analytical redundancy (for the airgap signal). In this way redundant airgap sensors are not essential for reliable operation of this system. When the airgap sensor fails the required signal is recovered using a combination of a Kalman estimator and analytical redundancy. The performance of the suspension is optimised using genetic algorithms and some preliminary robustness issues to load and operating airgap variations are discussed. Simulations on a realistic model of such type of suspension illustrate the efficacy of the proposed sensor tolerant control method.

  11. Functional Redundancy of MyD88-dependent Signaling Pathways in a Murine Model of Histidyl-tRNA Synthetase-induced Myositis

    PubMed Central

    Fernandez, Irina; Harlow, Lisa; Zang, Yunjuan; Liu-Bryan, Ru; Ridgway, William M.; Clemens, Paula R.; Ascherman, Dana P.

    2013-01-01

    We have previously shown that intramuscular administration of bacterially expressed murine histidyl-tRNA synthetase (HRS) triggers florid muscle inflammation (relative to appropriate control proteins) in various congenic strains of mice. Because severe disease develops even in the absence of adaptive immune responses to HRS, we sought to identify innate immune signaling components contributing to our model of HRS-induced myositis. In vitro stimulation assays demonstrated HRS-mediated activation of HEK293 cells transfected with either TLR2 or TLR4, revealing an excitatory capacity exceeding that of other bacterially expressed fusion proteins. Corresponding to this apparent functional redundancy of TLR signaling pathways, HRS immunization of B6.TLR2−/− and B6.TLR4−/− single knockout mice yielded significant lymphocytic infiltration of muscle tissue comparable to that produced in C57BL/6 WT mice. In contrast, concomitant elimination of TLR2 and TLR4 signaling in B6.TLR2−/−.TLR4−/− double knockout mice markedly reduced the severity of HRS-induced muscle inflammation. Complementary subfragment analysis demonstrated that amino acids 60–90 of HRS were absolutely required for in vitro as well as in vivo signaling via these MyD88-dependent TLR pathways—effects mediated, in part, through preferential binding of exogenous ligands capable of activating specific TLRs. Collectively, these experiments indicate that multiple MyD88-dependent signaling cascades contribute to this model of HRS-induced myositis, underscoring the antigenic versatility of HRS and confirming the importance of innate immunity in this system. PMID:23842751

  12. Design and reliability analysis of DP-3 dynamic positioning control architecture

    NASA Astrophysics Data System (ADS)

    Wang, Fang; Wan, Lei; Jiang, Da-Peng; Xu, Yu-Ru

    2011-12-01

    As the exploration and exploitation of oil and gas proliferate throughout deepwater area, the requirements on the reliability of dynamic positioning system become increasingly stringent. The control objective ensuring safety operation at deep water will not be met by a single controller for dynamic positioning. In order to increase the availability and reliability of dynamic positioning control system, the triple redundancy hardware and software control architectures were designed and developed according to the safe specifications of DP-3 classification notation for dynamically positioned ships and rigs. The hardware redundant configuration takes the form of triple-redundant hot standby configuration including three identical operator stations and three real-time control computers which connect each other through dual networks. The function of motion control and redundancy management of control computers were implemented by software on the real-time operating system VxWorks. The software realization of task loose synchronization, majority voting and fault detection were presented in details. A hierarchical software architecture was planed during the development of software, consisting of application layer, real-time layer and physical layer. The behavior of the DP-3 dynamic positioning control system was modeled by a Markov model to analyze its reliability. The effects of variation in parameters on the reliability measures were investigated. The time domain dynamic simulation was carried out on a deepwater drilling rig to prove the feasibility of the proposed control architecture.

  13. Redundant mechanisms to form silent chromatin at pericentromeric regions rely on BEND3 and DNA methylation.

    PubMed

    Saksouk, Nehmé; Barth, Teresa K; Ziegler-Birling, Celine; Olova, Nelly; Nowak, Agnieszka; Rey, Elodie; Mateos-Langerak, Julio; Urbach, Serge; Reik, Wolf; Torres-Padilla, Maria-Elena; Imhof, Axel; Déjardin, Jérome; Simboeck, Elisabeth

    2014-11-20

    Constitutive heterochromatin is typically defined by high levels of DNA methylation and H3 lysine 9 trimethylation (H3K9Me3), whereas facultative heterochromatin displays DNA hypomethylation and high H3 lysine 27 trimethylation (H3K27Me3). The two chromatin types generally do not coexist at the same loci, suggesting mutual exclusivity. During development or in cancer, pericentromeric regions can adopt either epigenetic state, but the switching mechanism is unknown. We used a quantitative locus purification method to characterize changes in pericentromeric chromatin-associated proteins in mouse embryonic stem cells deficient for either the methyltransferases required for DNA methylation or H3K9Me3. DNA methylation controls heterochromatin architecture and inhibits Polycomb recruitment. BEND3, a protein enriched on pericentromeric chromatin in the absence of DNA methylation or H3K9Me3, allows Polycomb recruitment and H3K27Me3, resulting in a redundant pathway to generate repressive chromatin. This suggests that BEND3 is a key factor in mediating a switch from constitutive to facultative heterochromatin. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Histone Deacetylases 5 and 9 Govern Responsiveness of the Heart to a Subset of Stress Signals and Play Redundant Roles in Heart Development

    PubMed Central

    Chang, Shurong; McKinsey, Timothy A.; Zhang, Chun Li; Richardson, James A.; Hill, Joseph A.; Olson, Eric N.

    2004-01-01

    The adult heart responds to stress signals by hypertrophic growth, which is often accompanied by activation of a fetal cardiac gene program and eventual cardiac demise. We showed previously that histone deacetylase 9 (HDAC9) acts as a suppressor of cardiac hypertrophy and that mice lacking HDAC9 are sensitized to cardiac stress signals. Here we report that mice lacking HDAC5 display a similar cardiac phenotype and develop profoundly enlarged hearts in response to pressure overload resulting from aortic constriction or constitutive cardiac activation of calcineurin, a transducer of cardiac stress signals. In contrast, mice lacking either HDAC5 or HDAC9 show a hypertrophic response to chronic β-adrenergic stimulation identical to that of wild-type littermates, suggesting that these HDACs modulate a specific subset of cardiac stress response pathways. We also show that compound mutant mice lacking both HDAC5 and HDAC9 show a propensity for lethal ventricular septal defects and thin-walled myocardium. These findings reveal central roles for HDACs 5 and 9 in the suppression of a subset of cardiac stress signals as well as redundant functions in the control of cardiac development. PMID:15367668

  15. Histone deacetylases 5 and 9 govern responsiveness of the heart to a subset of stress signals and play redundant roles in heart development.

    PubMed

    Chang, Shurong; McKinsey, Timothy A; Zhang, Chun Li; Richardson, James A; Hill, Joseph A; Olson, Eric N

    2004-10-01

    The adult heart responds to stress signals by hypertrophic growth, which is often accompanied by activation of a fetal cardiac gene program and eventual cardiac demise. We showed previously that histone deacetylase 9 (HDAC9) acts as a suppressor of cardiac hypertrophy and that mice lacking HDAC9 are sensitized to cardiac stress signals. Here we report that mice lacking HDAC5 display a similar cardiac phenotype and develop profoundly enlarged hearts in response to pressure overload resulting from aortic constriction or constitutive cardiac activation of calcineurin, a transducer of cardiac stress signals. In contrast, mice lacking either HDAC5 or HDAC9 show a hypertrophic response to chronic beta-adrenergic stimulation identical to that of wild-type littermates, suggesting that these HDACs modulate a specific subset of cardiac stress response pathways. We also show that compound mutant mice lacking both HDAC5 and HDAC9 show a propensity for lethal ventricular septal defects and thin-walled myocardium. These findings reveal central roles for HDACs 5 and 9 in the suppression of a subset of cardiac stress signals as well as redundant functions in the control of cardiac development.

  16. Exploiting Redundancy for Flexible Behavior: Unsupervised Learning in a Modular Sensorimotor Control Architecture

    ERIC Educational Resources Information Center

    Butz, Martin V.; Herbort, Oliver; Hoffmann, Joachim

    2007-01-01

    Autonomously developing organisms face several challenges when learning reaching movements. First, motor control is learned unsupervised or self-supervised. Second, knowledge of sensorimotor contingencies is acquired in contexts in which action consequences unfold in time. Third, motor redundancies must be resolved. To solve all 3 of these…

  17. X-wing fly-by-wire vehicle management system

    NASA Technical Reports Server (NTRS)

    Fischer, Jr., William C. (Inventor)

    1990-01-01

    A complete, computer based, vehicle management system (VMS) for X-Wing aircraft using digital fly-by-wire technology controlling many subsystems and providing functions beyond the classical aircraft flight control system. The vehicle management system receives input signals from a multiplicity of sensors and provides commands to a large number of actuators controlling many subsystems. The VMS includes--segregating flight critical and mission critical factors and providing a greater level of back-up or redundancy for the former; centralizing the computation of functions utilized by several subsystems (e.g. air data, rotor speed, etc.); integrating the control of the flight control functions, the compressor control, the rotor conversion control, vibration alleviation by higher harmonic control, engine power anticipation and self-test, all in the same flight control computer (FCC) hardware units. The VMS uses equivalent redundancy techniques to attain quadruple equivalency levels; includes alternate modes of operation and recovery means to back-up any functions which fail; and uses back-up control software for software redundancy.

  18. Achieving reliability - The evolution of redundancy in American manned spacecraft computers

    NASA Technical Reports Server (NTRS)

    Tomayko, J. E.

    1985-01-01

    The Shuttle is the first launch system deployed by NASA with full redundancy in the on-board computer systems. Fault-tolerance, i.e., restoring to a backup with less capabilities, was the method selected for Apollo. The Gemini capsule was the first to carry a computer, which also served as backup for Titan launch vehicle guidance. Failure of the Gemini computer resulted in manual control of the spacecraft. The Apollo system served vehicle flight control and navigation functions. The redundant computer on Skylab provided attitude control only in support of solar telescope pointing. The STS digital, fly-by-wire avionics system requires 100 percent reliability. The Orbiter carries five general purpose computers, four being fully-redundant and the fifth being soley an ascent-descent tool. The computers are synchronized at input and output points at a rate of about six times a second. The system is projected to cause a loss of an Orbiter only four times in a billion flights.

  19. Quadratic Programming for Allocating Control Effort

    NASA Technical Reports Server (NTRS)

    Singh, Gurkirpal

    2005-01-01

    A computer program calculates an optimal allocation of control effort in a system that includes redundant control actuators. The program implements an iterative (but otherwise single-stage) algorithm of the quadratic-programming type. In general, in the quadratic-programming problem, one seeks the values of a set of variables that minimize a quadratic cost function, subject to a set of linear equality and inequality constraints. In this program, the cost function combines control effort (typically quantified in terms of energy or fuel consumed) and control residuals (differences between commanded and sensed values of variables to be controlled). In comparison with prior control-allocation software, this program offers approximately equal accuracy but much greater computational efficiency. In addition, this program offers flexibility, robustness to actuation failures, and a capability for selective enforcement of control requirements. The computational efficiency of this program makes it suitable for such complex, real-time applications as controlling redundant aircraft actuators or redundant spacecraft thrusters. The program is written in the C language for execution in a UNIX operating system.

  20. Components of a Fanconi-like pathway control Pso2-independent DNA interstrand crosslink repair in yeast.

    PubMed

    Ward, Thomas A; Dudášová, Zuzana; Sarkar, Sovan; Bhide, Mangesh R; Vlasáková, Danuša; Chovanec, Miroslav; McHugh, Peter J

    2012-01-01

    Fanconi anemia (FA) is a devastating genetic disease, associated with genomic instability and defects in DNA interstrand cross-link (ICL) repair. The FA repair pathway is not thought to be conserved in budding yeast, and although the yeast Mph1 helicase is a putative homolog of human FANCM, yeast cells disrupted for MPH1 are not sensitive to ICLs. Here, we reveal a key role for Mph1 in ICL repair when the Pso2 exonuclease is inactivated. We find that the yeast FANCM ortholog Mph1 physically and functionally interacts with Mgm101, a protein previously implicated in mitochondrial DNA repair, and the MutSα mismatch repair factor (Msh2-Msh6). Co-disruption of MPH1, MGM101, MSH6, or MSH2 with PSO2 produces a lesion-specific increase in ICL sensitivity, the elevation of ICL-induced chromosomal rearrangements, and persistence of ICL-associated DNA double-strand breaks. We find that Mph1-Mgm101-MutSα directs the ICL-induced recruitment of Exo1 to chromatin, and we propose that Exo1 is an alternative 5'-3' exonuclease utilised for ICL repair in the absence of Pso2. Moreover, ICL-induced Rad51 chromatin loading is delayed when both Pso2 and components of the Mph1-Mgm101-MutSα and Exo1 pathway are inactivated, demonstrating that the homologous recombination stages of ICL repair are inhibited. Finally, the FANCJ- and FANCP-related factors Chl1 and Slx4, respectively, are also components of the genetic pathway controlled by Mph1-Mgm101-MutSα. Together this suggests that a prototypical FA-related ICL repair pathway operates in budding yeast, which acts redundantly with the pathway controlled by Pso2, and is required for the targeting of Exo1 to chromatin to execute ICL repair.

  1. Transcriptome Analysis and Discovery of Genes Involved in Immune Pathways from Hepatopancreas of Microbial Challenged Mitten Crab Eriocheir sinensis

    PubMed Central

    Li, Xihong; Cui, Zhaoxia; Liu, Yuan; Song, Chengwen; Shi, Guohui

    2013-01-01

    Background The Chinese mitten crab Eriocheir sinensis is an important economic crustacean and has been seriously attacked by various diseases, which requires more and more information for immune relevant genes on genome background. Recently, high-throughput RNA sequencing (RNA-seq) technology provides a powerful and efficient method for transcript analysis and immune gene discovery. Methods/Principal Findings A cDNA library from hepatopancreas of E. sinensis challenged by a mixture of three pathogen strains (Gram-positive bacteria Micrococcus luteus, Gram-negative bacteria Vibrio alginolyticus and fungi Pichia pastoris; 108 cfu·mL−1) was constructed and randomly sequenced using Illumina technique. Totally 39.76 million clean reads were assembled to 70,300 unigenes. After ruling out short-length and low-quality sequences, 52,074 non-redundant unigenes were compared to public databases for homology searching and 17,617 of them showed high similarity to sequences in NCBI non-redundant protein (Nr) database. For function classification and pathway assignment, 18,734 (36.00%) unigenes were categorized to three Gene Ontology (GO) categories, 12,243 (23.51%) were classified to 25 Clusters of Orthologous Groups (COG), and 8,983 (17.25%) were assigned to six Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Potentially, 24, 14, 47 and 132 unigenes were characterized to be involved in Toll, IMD, JAK-STAT and MAPK pathways, respectively. Conclusions/Significance This is the first systematical transcriptome analysis of components relating to innate immune pathways in E. sinensis. Functional genes and putative pathways identified here will contribute to better understand immune system and prevent various diseases in crab. PMID:23874555

  2. ENHANCED DISEASE SUSCEPTIBILITY 1 and SALICYLIC ACID act redundantly to regulate resistance gene-mediated signaling

    USDA-ARS?s Scientific Manuscript database

    Resistance (R) protein–associated pathways are well known to participate in defense against a variety of microbial pathogens. Salicylic acid (SA) and its associated proteinaceous signaling components, including enhanced disease susceptibility 1 (EDS1), non–race-specific disease resistance 1 (NDR1), ...

  3. Improved configuration control for redundant robots

    NASA Technical Reports Server (NTRS)

    Seraji, H.; Colbaugh, R.

    1990-01-01

    This article presents a singularity-robust task-prioritized reformulation of the configuration control scheme for redundant robot manipulators. This reformulation suppresses large joint velocities near singularities, at the expense of small task trajectory errors. This is achieved by optimally reducing the joint velocities to induce minimal errors in the task performance by modifying the task trajectories. Furthermore, the same framework provides a means for assignment of priorities between the basic task of end-effector motion and the user-defined additional task for utilizing redundancy. This allows automatic relaxation of the additional task constraints in favor of the desired end-effector motion, when both cannot be achieved exactly. The improved configuration control scheme is illustrated for a variety of additional tasks, and extensive simulation results are presented.

  4. Efficient Kinematic Computations For 7-DOF Manipulators

    NASA Technical Reports Server (NTRS)

    Seraji, Homayoun; Long, Mark K.; Kreutz-Delgado, Kenneth

    1994-01-01

    Efficient algorithms for forward kinematic mappings of seven-degree-of-freedom (7-DOF) robotic manipulator having revolute joints developed on basis of representation of redundant DOF in terms of parameter called "arm angle." Continuing effort to exploit redundancy in manipulator according to concept of basic and additional tasks. Concept also discussed in "Configuration-Control Scheme Copes With Singularities" (NPO-18556) and "Increasing the Dexterity of Redundant Robots" (NPO-17801).

  5. Discovery of functional interactions among actin regulators by analysis of image fluctuations in an unperturbed motile cell system.

    PubMed

    Isogai, Tadamoto; Danuser, Gaudenz

    2018-05-26

    Cell migration is driven by propulsive forces derived from polymerizing actin that pushes and extends the plasma membrane. The underlying actin network is constantly undergoing adaptation to new mechano-chemical environments and intracellular conditions. As such, mechanisms that regulate actin dynamics inherently contain multiple feedback loops and redundant pathways. Given the highly adaptable nature of such a system, studies that use only perturbation experiments (e.g. knockdowns, overexpression, pharmacological activation/inhibition, etc.) are challenged by the nonlinearity and redundancy of the pathway. In these pathway configurations, perturbation experiments at best describe the function(s) of a molecular component in an adapting (e.g. acutely drug-treated) or fully adapted (e.g. permanent gene silenced) cell system, where the targeted component now resides in a non-native equilibrium. Here, we propose how quantitative live-cell imaging and analysis of constitutive fluctuations of molecular activities can overcome these limitations. We highlight emerging actin filament barbed-end biology as a prime example of a complex, nonlinear molecular process that requires a fluctuation analytic approach, especially in an unperturbed cellular system, to decipher functional interactions of barbed-end regulators, actin polymerization and membrane protrusion.This article is part of the theme issue 'Self-organization in cell biology'. © 2018 The Author(s).

  6. Application of advanced control techniques to aircraft propulsion systems

    NASA Technical Reports Server (NTRS)

    Lehtinen, B.

    1984-01-01

    Two programs are described which involve the application of advanced control techniques to the design of engine control algorithms. Multivariable control theory is used in the F100 MVCS (multivariable control synthesis) program to design controls which coordinate the control inputs for improved engine performance. A systematic method for handling a complex control design task is given. Methods of analytical redundancy are aimed at increasing the control system reliability. The F100 DIA (detection, isolation, and accommodation) program, which investigates the uses of software to replace or augment hardware redundancy for certain critical engine sensor, is described.

  7. Analysis of expressed sequence tags (ESTs) from cocoa (Theobroma cacao L) upon infection with Phytophthora megakarya.

    PubMed

    Naganeeswaran, Sudalaimuthu Asari; Subbian, Elain Apshara; Ramaswamy, Manimekalai

    2012-01-01

    Phytophthora megakarya, the causative agent of cacao black pod disease in West African countries causes an extensive loss of yield. In this study we have analyzed 4 libraries of ESTs derived from Phytophthora megakarya infected cocoa leaf and pod tissues. Totally 6379 redundant sequences were retrieved from ESTtik database and EST processing was performed using seqclean tool. Clustering and assembling using CAP3 generated 3333 non-redundant (907 contigs and 2426 singletons) sequences. The primary sequence analysis of 3333 non-redundant sequences showed that the GC percentage was 42.7 and the sequence length ranged from 101 - 2576 nucleotides. Further, functional analysis (Blast, Interproscan, Gene ontology and KEGG search) were executed and 1230 orthologous genes were annotated. Totally 272 enzymes corresponding to 114 metabolic pathways were identified. Functional annotation revealed that most of the sequences are related to molecular function, stress response and biological processes. The annotated enzymes are aldehyde dehydrogenase (E.C: 1.2.1.3), catalase (E.C: 1.11.1.6), acetyl-CoA C-acetyltransferase (E.C: 2.3.1.9), threonine ammonia-lyase (E.C: 4.3.1.19), acetolactate synthase (E.C: 2.2.1.6), O-methyltransferase (E.C: 2.1.1.68) which play an important role in amino acid biosynthesis and phenyl propanoid biosynthesis. All this information was stored in MySQL database management system to be used in future for reconstruction of biotic stress response pathway in cocoa.

  8. Restoring Redundancy to the MAP Propulsion System

    NASA Technical Reports Server (NTRS)

    O'Donnell, James R., Jr.; Davis, Gary T.; Ward, David K.; Bauer, Frank H. (Technical Monitor)

    2002-01-01

    The Microwave Anisotropy Probe (MAP) is a follow-on to the Differential Microwave Radiometer (DMR) instrument on the Cosmic Background Explorer (COBE). Due to the MAP project's limited mass, power, and financial resources, a traditional reliability concept including fully redundant components was not feasible. The MAP design employs selective hardware redundancy, along with backup software modes and algorithms, to improve the odds of mission success. In particular, MAP's propulsion system, which is used for orbit maneuvers and momentum management, uses eight thrusters positioned and oriented in such a way that its thruster-based attitude control modes can maintain three-axis attitude control in the event of the failure of any one thruster.

  9. Bilateral force reflection for teleoperators with masters and slaves with dissimilar and possibly redundant kinematics

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

    Jansen, J.F.; Babcock, S.M.

    1989-11-01

    Several bilateral control techniques and methods for exploiting redundant slaves are investigated as a part of research to develop and analyze bilateral, force-reflecting control methodologies for teleoperator systems with kinematic dissimilar masters and slaves. The study indicates that, with force/torque sensing at the wrist, and an impedance type of controller with the appropriate joint compensation, a significant improvement in performance and controllability of a teleoperator system can be achieved. 32 refs., 6 figs., 2 tabs.

  10. Optimal Redundancy Management in Reconfigurable Control Systems Based on Normalized Nonspecificity

    NASA Technical Reports Server (NTRS)

    Wu, N.Eva; Klir, George J.

    1998-01-01

    In this paper the notion of normalized nonspecificity is introduced. The nonspecifity measures the uncertainty of the estimated parameters that reflect impairment in a controlled system. Based on this notion, a quantity called a reconfiguration coverage is calculated. It represents the likelihood of success of a control reconfiguration action. This coverage links the overall system reliability to the achievable and required control, as well as diagnostic performance. The coverage, when calculated on-line, is used for managing the redundancy in the system.

  11. Reliable actuators for twin rotor MIMO system

    NASA Astrophysics Data System (ADS)

    Rao, Vidya S.; V. I, George; Kamath, Surekha; Shreesha, C.

    2017-11-01

    Twin Rotor MIMO System (TRMS) is a bench mark system to test flight control algorithms. One of the perturbations on TRMS which is likely to affect the control system is actuator failure. Therefore, there is a need for a reliable control system, which includes H infinity controller along with redundant actuators. Reliable control refers to the design of a control system to tolerate failures of a certain set of actuators or sensors while retaining desired control system properties. Output of reliable controller has to be transferred to the redundant actuator effectively to make the TRMS reliable even under actual actuator failure.

  12. Transcription Factor Interplay between LEAFY and APETALA1/CAULIFLOWER during Floral Initiation1

    PubMed Central

    Zheng, Beibei; Kwaśniewska, Kamila; Thomson, Bennett

    2017-01-01

    The transcription factors LEAFY (LFY) and APETALA1 (AP1), together with the AP1 paralog CAULIFLOWER (CAL), control the onset of flower development in a partially redundant manner. This redundancy is thought to be mediated, at least in part, through the regulation of a shared set of target genes. However, whether these genes are independently or cooperatively regulated by LFY and AP1/CAL is currently unknown. To better understand the regulatory relationship between LFY and AP1/CAL and to obtain deeper insights into the control of floral initiation, we monitored the activity of LFY in the absence of AP1/CAL function. We found that the regulation of several known LFY target genes is unaffected by AP1/CAL perturbation, while others appear to require AP1/CAL activity. Furthermore, we obtained evidence that LFY and AP1/CAL control the expression of some genes in an antagonistic manner. Notably, these include key regulators of floral initiation such as TERMINAL FLOWER1 (TFL1), which had been previously reported to be directly repressed by both LFY and AP1. We show here that TFL1 expression is suppressed by AP1 but promoted by LFY. We further demonstrate that LFY has an inhibitory effect on flower formation in the absence of AP1/CAL activity. We propose that LFY and AP1/CAL act as part of an incoherent feed-forward loop, a network motif where two interconnected pathways or transcription factors act in opposite directions on a target gene, to control the establishment of a stable developmental program for the formation of flowers. PMID:28385730

  13. Transcription Factor Interplay between LEAFY and APETALA1/CAULIFLOWER during Floral Initiation.

    PubMed

    Goslin, Kevin; Zheng, Beibei; Serrano-Mislata, Antonio; Rae, Liina; Ryan, Patrick T; Kwaśniewska, Kamila; Thomson, Bennett; Ó'Maoiléidigh, Diarmuid S; Madueño, Francisco; Wellmer, Frank; Graciet, Emmanuelle

    2017-06-01

    The transcription factors LEAFY (LFY) and APETALA1 (AP1), together with the AP1 paralog CAULIFLOWER (CAL), control the onset of flower development in a partially redundant manner. This redundancy is thought to be mediated, at least in part, through the regulation of a shared set of target genes. However, whether these genes are independently or cooperatively regulated by LFY and AP1/CAL is currently unknown. To better understand the regulatory relationship between LFY and AP1/CAL and to obtain deeper insights into the control of floral initiation, we monitored the activity of LFY in the absence of AP1/CAL function. We found that the regulation of several known LFY target genes is unaffected by AP1/CAL perturbation, while others appear to require AP1/CAL activity. Furthermore, we obtained evidence that LFY and AP1/CAL control the expression of some genes in an antagonistic manner. Notably, these include key regulators of floral initiation such as TERMINAL FLOWER1 ( TFL1 ), which had been previously reported to be directly repressed by both LFY and AP1. We show here that TFL1 expression is suppressed by AP1 but promoted by LFY. We further demonstrate that LFY has an inhibitory effect on flower formation in the absence of AP1/CAL activity. We propose that LFY and AP1/CAL act as part of an incoherent feed-forward loop, a network motif where two interconnected pathways or transcription factors act in opposite directions on a target gene, to control the establishment of a stable developmental program for the formation of flowers. © 2017 American Society of Plant Biologists. All Rights Reserved.

  14. On the danger of redundancies in some aerospace mechanisms

    NASA Technical Reports Server (NTRS)

    Chew, M.

    1988-01-01

    An attempt is made to show that redundancies in some aerospace mechanisms do not generally improve the odds for success. Some of these redundancies may even be the very cause for failure of the system. To illustrate this fallacy, two designs based on the Control of Flexible Structures I (COFS I) Mast deployer and retractor assembly (DRA) are presented together with novel designs to circumvent such design inadequacies, while improving system reliability.

  15. The STAT3-Ser/Hes3 signaling axis: an emerging regulator of endogenous regeneration and cancer growth

    PubMed Central

    Poser, Steven W.; Park, Deric M.; Androutsellis-Theotokis, Andreas

    2013-01-01

    Stem cells, by definition, are able to both self-renew (give rise to more cells of their own kind) and demonstrate multipotential (the ability to differentiate into multiple cell types). To accommodate this unique dual ability, stem cells interpret signal transduction pathways in specialized ways. Notable examples include canonical and non-canonical branches of the Notch signaling pathway, with each controlling different downstream targets (e.g., Hes1 vs. Hes3) and promoting either differentiation or self-renewal. Similarly, stem cells utilize STAT3 signaling uniquely. Most mature cells studied thus far rely on tyrosine phosphorylation (STAT3-Tyr) to promote survival and growth; in contrast, STAT3-Tyr induces the differentiation of neural stem cells (NSCs). NSCs use an alternative phosphorylation site, STAT3-Ser, to regulate survival and growth, a site that is largely redundant for this function in most other cell types. STAT3-Ser regulates Hes3, and together they form a convergence point for several signals, including Notch, Tie2, and insulin receptor activation. Disregulation and manipulation of the STAT3-Ser/Hes3 signaling pathway is important in both tumorigenesis and regenerative medicine, and worthy of extensive study. PMID:24101906

  16. High Reliability and the Evaluation of ATC System Configuration by Communizing Resources

    NASA Astrophysics Data System (ADS)

    Yamamoto, Masanori

    Automatic Train Control (ATC) in the railway signalling system is required high safety, high availability, reduction of unit, energy saving and cost reduction. This paper described the resources communization redundancy of the ATC system that shared the redundant units in preparation for common use units in order to accommodate with this issue by keeping safety and availability in the same level of conventional ATC. It was evaluated on N+2 redundant system which established 2 spares for the common use system N piece in transmission division. It was done the safety evaluation of the N+2 redundant system by way of hazard analysis of FTA method and safety issue was confirmed by FMEA. The new redundant system concludes that 19% of downsizing and 36% of the energy saving are surely possible.

  17. Multiple levels of redundant processes inhibit Caenorhabditis elegans vulval cell fates.

    PubMed

    Andersen, Erik C; Saffer, Adam M; Horvitz, H Robert

    2008-08-01

    Many mutations cause obvious abnormalities only when combined with other mutations. Such synthetic interactions can be the result of redundant gene functions. In Caenorhabditis elegans, the synthetic multivulva (synMuv) genes have been grouped into multiple classes that redundantly inhibit vulval cell fates. Animals with one or more mutations of the same class undergo wild-type vulval development, whereas animals with mutations of any two classes have a multivulva phenotype. By varying temperature and genetic background, we determined that mutations in most synMuv genes within a single synMuv class enhance each other. However, in a few cases no enhancement was observed. For example, mutations that affect an Mi2 homolog and a histone methyltransferase are of the same class and do not show enhancement. We suggest that such sets of genes function together in vivo and in at least some cases encode proteins that interact physically. The approach of genetic enhancement can be applied more broadly to identify potential protein complexes as well as redundant processes or pathways. Many synMuv genes are evolutionarily conserved, and the genetic relationships we have identified might define the functions not only of synMuv genes in C. elegans but also of their homologs in other organisms.

  18. Multiple Levels of Redundant Processes Inhibit Caenorhabditis elegans Vulval Cell Fates

    PubMed Central

    Andersen, Erik C.; Saffer, Adam M.; Horvitz, H. Robert

    2008-01-01

    Many mutations cause obvious abnormalities only when combined with other mutations. Such synthetic interactions can be the result of redundant gene functions. In Caenorhabditis elegans, the synthetic multivulva (synMuv) genes have been grouped into multiple classes that redundantly inhibit vulval cell fates. Animals with one or more mutations of the same class undergo wild-type vulval development, whereas animals with mutations of any two classes have a multivulva phenotype. By varying temperature and genetic background, we determined that mutations in most synMuv genes within a single synMuv class enhance each other. However, in a few cases no enhancement was observed. For example, mutations that affect an Mi2 homolog and a histone methyltransferase are of the same class and do not show enhancement. We suggest that such sets of genes function together in vivo and in at least some cases encode proteins that interact physically. The approach of genetic enhancement can be applied more broadly to identify potential protein complexes as well as redundant processes or pathways. Many synMuv genes are evolutionarily conserved, and the genetic relationships we have identified might define the functions not only of synMuv genes in C. elegans but also of their homologs in other organisms. PMID:18689876

  19. Analysis of informational redundancy in the protein-assembling machinery

    NASA Astrophysics Data System (ADS)

    Berkovich, Simon

    2004-03-01

    Entropy analysis of the DNA structure does not reveal a significant departure from randomness indicating lack of informational redundancy. This signifies the absence of a hidden meaning in the genome text and supports the 'barcode' interpretation of DNA given in [1]. Lack of informational redundancy is a characteristic property of an identification label rather than of a message of instructions. Yet randomness of DNA has to induce non-random structures of the proteins. Protein synthesis is a two-step process: transcription into RNA with gene splicing and formation a structure of amino acids. Entropy estimations, performed by A. Djebbari, show typical values of redundancy of the biomolecules along these pathways: DNA gene 4proteins 15-40in gene expression, the RNA copy carries the same information as the original DNA template. Randomness is essentially eliminated only at the step of the protein creation by a degenerate code. According to [1], the significance of the substitution of U for T with a subsequent gene splicing is that these transformations result in a different pattern of RNA oscillations, so the vital DNA communications are protected against extraneous noise coming from the protein making activities. 1. S. Berkovich, "On the 'barcode' functionality of DNA, or the Phenomenon of Life in the Physical Universe", Dorrance Publishing Co., Pittsburgh, 2003

  20. Transcriptome Profiling of Chironomus kiinensis under Phenol Stress Using Solexa Sequencing Technology

    PubMed Central

    Cao, Chuanwang; Wang, Zhiying; Niu, Changying; Desneux, Nicolas; Gao, Xiwu

    2013-01-01

    Phenol is a major pollutant in aquatic ecosystems due to its chemical stability, water solubility and environmental mobility. To date, little is known about the molecular modifications of invertebrates under phenol stress. In the present study, we used Solexa sequencing technology to investigate the transcriptome and differentially expressed genes (DEGs) of midges (Chironomus kiinensis) in response to phenol stress. A total of 51,518,972 and 51,150,832 clean reads in the phenol-treated and control libraries, respectively, were obtained and assembled into 51,014 non-redundant (Nr) consensus sequences. A total of 6,032 unigenes were classified by Gene Ontology (GO), and 18,366 unigenes were categorized into 238 Kyoto Encyclopedia of Genes and Genomes (KEGG) categories. These genes included representatives from almost all functional categories. A total of 10,724 differentially expressed genes (P value <0.05) were detected in a comparative analysis of the expression profiles between phenol-treated and control C. kiinensis including 8,390 upregulated and 2,334 downregulated genes. The expression levels of 20 differentially expressed genes were confirmed by real-time RT-PCR, and the trends in gene expression that were observed matched the Solexa expression profiles, although the magnitude of the variations was different. Through pathway enrichment analysis, significantly enriched pathways were identified for the DEGs, including metabolic pathways, aryl hydrocarbon receptor (AhR), pancreatic secretion and neuroactive ligand-receptor interaction pathways, which may be associated with the phenol responses of C. kiinensis. Using Solexa sequencing technology, we identified several groups of key candidate genes as well as important biological pathways involved in the molecular modifications of chironomids under phenol stress. PMID:23527048

  1. In-flight adaptive performance optimization (APO) control using redundant control effectors of an aircraft

    NASA Technical Reports Server (NTRS)

    Gilyard, Glenn B. (Inventor)

    1999-01-01

    Practical application of real-time (or near real-time) Adaptive Performance Optimization (APO) is provided for a transport aircraft in steady climb, cruise, turn descent or other flight conditions based on measurements and calculations of incremental drag from a forced response maneuver of one or more redundant control effectors defined as those in excess of the minimum set of control effectors required to maintain the steady flight condition in progress. The method comprises the steps of applying excitation in a raised-cosine form over an interval of from 100 to 500 sec. at the rate of 1 to 10 sets/sec of excitation, and data for analysis is gathered in sets of measurements made during the excitation to calculate lift and drag coefficients C.sub.L and C.sub.D from two equations, one for each coefficient. A third equation is an expansion of C.sub.D as a function of parasitic drag, induced drag, Mach and altitude drag effects, and control effector drag, and assumes a quadratic variation of drag with positions .delta..sub.i of redundant control effectors i=1 to n. The third equation is then solved for .delta..sub.iopt the optimal position of redundant control effector i, which is then used to set the control effector i for optimum performance during the remainder of said steady flight or until monitored flight conditions change by some predetermined amount as determined automatically or a predetermined minimum flight time has elapsed.

  2. Design Description of the X-33 Avionics Architecture

    NASA Technical Reports Server (NTRS)

    Reichenfeld, Curtis J.; Jones, Paul G.

    1999-01-01

    In this paper, we provide a design description of the X-33 avionics architecture. The X-33 is an autonomous Single Stage to Orbit (SSTO) launch vehicle currently being developed by Lockheed Martin for NASA as a technology demonstrator for the VentureStar Reusable Launch Vehicle (RLV). The X-33 avionics provides autonomous control of die vehicle throughout takeoff, ascent, descent, approach, landing, rollout, and vehicle safing. During flight the avionics provides communication to the range through uplinked commands and downlinked telemetry. During pre-launch and post-safing activities, the avionics provides interfaces to ground support consoles that perform vehicle flight preparations and maintenance. The X-33 Avionics is a hybrid of centralized and distributed processing elements connected by three dual redundant Mil-Std 1553 data buses. These data buses are controlled by a central processing suite located in the avionics bay and composed of triplex redundant Vehicle Mission Computers (VMCs). The VMCs integrate mission management, guidance, navigation, flight control, subsystem control and redundancy management functions. The vehicle sensors, effectors and subsystems are interfaced directly to the centralized VMCs as remote terminals or through dual redundant Data Interface Units (DIUs). The DIUs are located forward and aft of the avionics bay and provide signal conditioning, health monitoring, low level subsystem control and data interface functions. Each VMC is connected to all three redundant 1553 data buses for monitoring and provides a complete identical data set to the processing algorithms. This enables bus faults to be detected and reconfigured through a voted bus control configuration. Data is also shared between VMCs though a cross channel data link that is implemented in hardware and controlled by AlliedSignal's Fault Tolerant Executive (FTE). The FTE synchronizes processors within the VMC and synchronizes redundant VMCs to each other. The FTE provides an output-voting plane to detect, isolate and contain faults due to internal hardware or software faults and reconfigures the VMCs to accommodate these faults. Critical data in the 1553 messages are scheduled and synchronized to specific processing frames in order to minimize data latency. In order to achieve an open architecture, military and commercial off-the-shelf equipment is incorporated using common processors, standard VME backplanes and chassis, the VxWorks operating system, and MartixX for automatic code generation. The use of off-the-shelf tools and equipment helps reduce development time and enables software reuse. The open architecture allows for technology insertion, while the distributed modular elements allow for expansion to increased redundancy levels to meet the higher reliability goals of future RLVs.

  3. IUSThrust Vector Control (TVC) servo system

    NASA Technical Reports Server (NTRS)

    Conner, G. E.

    1979-01-01

    The IUS TVC SERVO SYSTEM which consists of four electrically redundant electromechanical actuators, four potentiometer assemblies, and two controllers to provide movable nozzle control on both IUS solid rocket motors is developed. An overview of the more severe IUS TVC servo system design requirements, the system and component designs, and test data acquired on a preliminary development unit is presented. Attention is focused on the unique methods of sensing movable nozzle position and providing for redundant position locks.

  4. Optimal Management of Redundant Control Authority for Fault Tolerance

    NASA Technical Reports Server (NTRS)

    Wu, N. Eva; Ju, Jianhong

    2000-01-01

    This paper is intended to demonstrate the feasibility of a solution to a fault tolerant control problem. It explains, through a numerical example, the design and the operation of a novel scheme for fault tolerant control. The fundamental principle of the scheme was formalized in [5] based on the notion of normalized nonspecificity. The novelty lies with the use of a reliability criterion for redundancy management, and therefore leads to a high overall system reliability.

  5. The bliss (not the problem) of motor abundance (not redundancy).

    PubMed

    Latash, Mark L

    2012-03-01

    Motor control is an area of natural science exploring how the nervous system interacts with other body parts and the environment to produce purposeful, coordinated actions. A central problem of motor control-the problem of motor redundancy-was formulated by Nikolai Bernstein as the problem of elimination of redundant degrees-of-freedom. Traditionally, this problem has been addressed using optimization methods based on a variety of cost functions. This review draws attention to a body of recent findings suggesting that the problem has been formulated incorrectly. An alternative view has been suggested as the principle of abundance, which considers the apparently redundant degrees-of-freedom as useful and even vital for many aspects of motor behavior. Over the past 10 years, dozens of publications have provided support for this view based on the ideas of synergic control, computational apparatus of the uncontrolled manifold hypothesis, and the equilibrium-point (referent configuration) hypothesis. In particular, large amounts of "good variance"-variance in the space of elements that has no effect on the overall performance-have been documented across a variety of natural actions. "Good variance" helps an abundant system to deal with secondary tasks and unexpected perturbations; its amount shows adaptive modulation across a variety of conditions. These data support the view that there is no problem of motor redundancy; there is bliss of motor abundance.

  6. Cytosolic NADPH Homeostasis in Glucose-starved Procyclic Trypanosoma brucei Relies on Malic Enzyme and the Pentose Phosphate Pathway Fed by Gluconeogenic Flux*

    PubMed Central

    Allmann, Stefan; Morand, Pauline; Ebikeme, Charles; Gales, Lara; Biran, Marc; Hubert, Jane; Brennand, Ana; Mazet, Muriel; Franconi, Jean-Michel; Michels, Paul A. M.; Portais, Jean-Charles; Boshart, Michael; Bringaud, Frédéric

    2013-01-01

    All living organisms depend on NADPH production to feed essential biosyntheses and for oxidative stress defense. Protozoan parasites such as the sleeping sickness pathogen Trypanosoma brucei adapt to different host environments, carbon sources, and oxidative stresses during their infectious life cycle. The procyclic stage develops in the midgut of the tsetse insect vector, where they rely on proline as carbon source, although they prefer glucose when grown in rich media. Here, we investigate the flexible and carbon source-dependent use of NADPH synthesis pathways in the cytosol of the procyclic stage. The T. brucei genome encodes two cytosolic NADPH-producing pathways, the pentose phosphate pathway (PPP) and the NADP-dependent malic enzyme (MEc). Reverse genetic blocking of those pathways and a specific inhibitor (dehydroepiandrosterone) of glucose-6-phosphate dehydrogenase together established redundancy with respect to H2O2 stress management and parasite growth. Blocking both pathways resulted in ∼10-fold increase of susceptibility to H2O2 stress and cell death. Unexpectedly, the same pathway redundancy was observed in glucose-rich and glucose-depleted conditions, suggesting that gluconeogenesis can feed the PPP to provide NADPH. This was confirmed by (i) a lethal phenotype of RNAi-mediated depletion of glucose-6-phosphate isomerase (PGI) in the glucose-depleted Δmec/Δmec null background, (ii) an ∼10-fold increase of susceptibility to H2O2 stress observed for the Δmec/Δmec/RNAiPGI double mutant when compared with the single mutants, and (iii) the 13C enrichment of glycolytic and PPP intermediates from cells incubated with [U-13C]proline, in the absence of glucose. Gluconeogenesis-supported NADPH supply may also be important for nucleotide and glycoconjugate syntheses in the insect host. PMID:23665470

  7. Obstacle avoidance for redundant robots using configuration control

    NASA Technical Reports Server (NTRS)

    Seraji, Homayoun (Inventor); Colbaugh, Richard D. (Inventor); Glass, Kristin L. (Inventor)

    1992-01-01

    A redundant robot control scheme is provided for avoiding obstacles in a workspace during the motion of an end effector along a preselected trajectory by stopping motion of the critical point on the robot closest to the obstacle when the distance between is reduced to a predetermined sphere of influence surrounding the obstacle. Algorithms are provided for conveniently determining the critical point and critical distance.

  8. Performance of redundant disk array organizations in transaction processing environments

    NASA Technical Reports Server (NTRS)

    Mourad, Antoine N.; Fuchs, W. K.; Saab, Daniel G.

    1993-01-01

    A performance evaluation is conducted for two redundant disk-array organizations in a transaction-processing environment, relative to the performance of both mirrored disk organizations and organizations using neither striping nor redundancy. The proposed parity-striping alternative to striping with rotated parity is shown to furnish rapid recovery from failure at the same low storage cost without interleaving the data over multiple disks. Both noncached systems and systems using a nonvolatile cache as the controller are considered.

  9. Emerging roles for antigen presentation in establishing host-microbiome symbiosis

    PubMed Central

    Bessman, Nicholas J.; Sonnenberg, Gregory F.

    2016-01-01

    Trillions of beneficial bacteria inhabit the intestinal tract of healthy mammals from birth. Accordingly, mammalian hosts have evolved a series of complementary and redundant pathways to limit pathologic immune responses against these bacteria, while simultaneously protecting against enteric pathogen invasion. These pathways can be generically responsive to the presence of any commensal bacteria and innate in nature, as for IL-22-related pathways. Alternatively, specific bacterial antigens can drive a distinct set of adaptive immune cell responses, including IgA affinity maturation and secretion, and a recently described pathway of intestinal selection whereby MHCII+ ILC3 deletes commensal bacteria-reactive CD4 T cells. These pathways can either promote or inhibit colonization by specific subsets of commensal bacteria, and cooperatively maintain intestinal homeostasis. In this review, we will highlight recent developments in understanding how these diverse pathways complement each other to cooperatively shape the symbiotic relationship between commensal bacteria and mammalian hosts. PMID:27319348

  10. Fail Safe, High Temperature Magnetic Bearings

    NASA Technical Reports Server (NTRS)

    Minihan, Thomas; Palazzolo, Alan; Kim, Yeonkyu; Lei, Shu-Liang; Kenny, Andrew; Na, Uhn Joo; Tucker, Randy; Preuss, Jason; Hunt, Andrew; Carter, Bart; hide

    2002-01-01

    This paper contributes to the magnetic bearing literature in two distinct areas: high temperature and redundant actuation. Design considerations and test results are given for the first published combined 538 C (1000 F) high speed rotating test performance of a magnetic bearing. Secondly, a significant extension of the flux isolation based, redundant actuator control algorithm is proposed to eliminate the prior deficiency of changing position stiffness after failure. The benefit of the novel extension was not experimentally demonstrated due to a high active stiffness requirement. In addition, test results are given for actuator failure tests at 399 C (750 F), 12,500 rpm. Finally, simulation results are presented confirming the experimental data and validating the redundant control algorithm.

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

    Unseren, M.A.

    This report proposes a method for resolving the kinematic redundancy of a serial link manipulator moving in a three-dimensional workspace. The underspecified problem of solving for the joint velocities based on the classical kinematic velocity model is transformed into a well-specified problem. This is accomplished by augmenting the original model with additional equations which relate a new vector variable quantifying the redundant degrees of freedom (DOF) to the joint velocities. The resulting augmented system yields a well specified solution for the joint velocities. Methods for selecting the redundant DOF quantifying variable and the transformation matrix relating it to the jointmore » velocities are presented so as to obtain a minimum Euclidean norm solution for the joint velocities. The approach is also applied to the problem of resolving the kinematic redundancy at the acceleration level. Upon resolving the kinematic redundancy, a rigid body dynamical model governing the gross motion of the manipulator is derived. A control architecture is suggested which according to the model, decouples the Cartesian space DOF and the redundant DOF.« less

  12. Autophagy in the control of food intake.

    PubMed

    Singh, Rajat

    2012-04-01

    The cellular nutrient sensing apparatus detects nutritional depletion and transmits this information to downstream effectors that generate energy from alternate sources. Autophagy is a crucial catabolic pathway that turns over redundant cytoplasmic components in lysosomes to provide energy to the starved cell. Recent studies have described a role for hypothalamic autophagy in the control of food intake and energy balance. Activated autophagy in hypothalamic neurons during starvation mobilized neuron-intrinsic lipids to generate free fatty acids that increased AgRP levels. AgRP neuron-specific inhibition of autophagy decreased fasting-induced increases in AgRP levels and food intake. Deletion of autophagy in AgRP neurons led to constitutive increases in levels of proopiomelanocortin and its active processed product, α-melanocyte stimulating hormone that contributed to reduced adiposity in these rodents. The current manuscript discusses these new findings and raises additional questions that may help understand how hypothalamic autophagy controls food intake and energy balance. These studies may have implications for designing new therapies against obesity and insulin resistance.

  13. Intercommunications in Real Time, Redundant, Distributed Computer System

    NASA Technical Reports Server (NTRS)

    Zanger, H.

    1980-01-01

    An investigation into the applicability of fiber optic communication techniques to real time avionic control systems, in particular the total automatic flight control system used for the VSTOL aircraft is presented. The system consists of spatially distributed microprocessors. The overall control function is partitioned to yield a unidirectional data flow between the processing elements (PE). System reliability is enhanced by the use of triple redundancy. Some general overall system specifications are listed here to provide the necessary background for the requirements of the communications system.

  14. Formulation of a strategy for monitoring control integrity in critical digital control systems

    NASA Technical Reports Server (NTRS)

    Belcastro, Celeste M.; Fischl, Robert; Kam, Moshe

    1991-01-01

    Advanced aircraft will require flight critical computer systems for stability augmentation as well as guidance and control that must perform reliably in adverse, as well as nominal, operating environments. Digital system upset is a functional error mode that can occur in electromagnetically harsh environments, involves no component damage, can occur simultaneously in all channels of a redundant control computer, and is software dependent. A strategy is presented for dynamic upset detection to be used in the evaluation of critical digital controllers during the design and/or validation phases of development. Critical controllers must be able to be used in adverse environments that result from disturbances caused by an electromagnetic source such as lightning, high intensity radiated field (HIRF), and nuclear electromagnetic pulses (NEMP). The upset detection strategy presented provides dynamic monitoring of a given control computer for degraded functional integrity that can result from redundancy management errors and control command calculation error that could occur in an electromagnetically harsh operating environment. The use is discussed of Kalman filtering, data fusion, and decision theory in monitoring a given digital controller for control calculation errors, redundancy management errors, and control effectiveness.

  15. Interlimb Differences in Coordination of Unsupported Reaching Movements

    PubMed Central

    Schaffer, Jacob E.; Sainburg, Robert L.

    2017-01-01

    Previous research suggests that interlimb differences in coordination associated with handedness might result from specialized control mechanisms that are subserved by different cerebral hemispheres. Based largely on the results of horizontal plane reaching studies, we have proposed that the hemisphere contralateral to the dominant arm is specialized for predictive control of limb dynamics, while the non-dominant hemisphere is specialized for controlling limb impedance. The current study explores interlimb differences in control of 3-D unsupported reaching movements. While the task was presented in the horizontal plane, participant’s arms were unsupported and free to move within a range of the vertical axis, which was redundant to the task plane. Results indicated significant dominant arm advantages for both initial direction accuracy and final position accuracy. The dominant arm showed greater excursion along a redundant axis that was perpendicular to the task, and parallel to gravitational forces. In contrast, the non-dominant arm better impeded motion out of the task-plane. Nevertheless, left arm task errors varied substantially more with shoulder rotation excursion than did dominant arm task errors. These findings suggest that the dominant arm controller was able to take advantage of the redundant degrees of freedom of the task, while non-dominant task errors appeared enslaved to motion along the redundant axis. These findings are consistent with a dominant controller that is specialized for intersegmental coordination, and a non-dominant controller that is specialized for impedance control. However, the findings are inconsistent with previously documented conclusions from planar tasks, in which non-dominant control leads to greater final position accuracy. PMID:28344068

  16. Unified Approach To Control Of Motions Of Mobile Robots

    NASA Technical Reports Server (NTRS)

    Seraji, Homayoun

    1995-01-01

    Improved computationally efficient scheme developed for on-line coordinated control of both manipulation and mobility of robots that include manipulator arms mounted on mobile bases. Present scheme similar to one described in "Coordinated Control of Mobile Robotic Manipulators" (NPO-19109). Both schemes based on configuration-control formalism. Present one incorporates explicit distinction between holonomic and nonholonomic constraints. Several other prior articles in NASA Tech Briefs discussed aspects of configuration-control formalism. These include "Increasing the Dexterity of Redundant Robots" (NPO-17801), "Redundant Robot Can Avoid Obstacles" (NPO-17852), "Configuration-Control Scheme Copes with Singularities" (NPO-18556), "More Uses for Configuration Control of Robots" (NPO-18607/NPO-18608).

  17. Carbon-dependent control of electron transfer and central carbon pathway genes for methane biosynthesis in the Archaean, Methanosarcina acetivorans strain C2A

    PubMed Central

    2010-01-01

    Background The archaeon, Methanosarcina acetivorans strain C2A forms methane, a potent greenhouse gas, from a variety of one-carbon substrates and acetate. Whereas the biochemical pathways leading to methane formation are well understood, little is known about the expression of the many of the genes that encode proteins needed for carbon flow, electron transfer and/or energy conservation. Quantitative transcript analysis was performed on twenty gene clusters encompassing over one hundred genes in M. acetivorans that encode enzymes/proteins with known or potential roles in substrate conversion to methane. Results The expression of many seemingly "redundant" genes/gene clusters establish substrate dependent control of approximately seventy genes for methane production by the pathways for methanol and acetate utilization. These include genes for soluble-type and membrane-type heterodisulfide reductases (hdr), hydrogenases including genes for a vht-type F420 non-reducing hydrogenase, molybdenum-type (fmd) as well as tungsten-type (fwd) formylmethanofuran dehydrogenases, genes for rnf and mrp-type electron transfer complexes, for acetate uptake, plus multiple genes for aha- and atp-type ATP synthesis complexes. Analysis of promoters for seven gene clusters reveal UTR leaders of 51-137 nucleotides in length, raising the possibility of both transcriptional and translational levels of control. Conclusions The above findings establish the differential and coordinated expression of two major gene families in M. acetivorans in response to carbon/energy supply. Furthermore, the quantitative mRNA measurements demonstrate the dynamic range for modulating transcript abundance. Since many of these gene clusters in M. acetivorans are also present in other Methanosarcina species including M. mazei, and in M. barkeri, these findings provide a basis for predicting related control in these environmentally significant methanogens. PMID:20178638

  18. Telerobotic control of the seven-degree-of-freedom CESAR manipulator

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

    Babcock, S.M.; Dubey, R.V.; Euler, J.A.

    1988-01-01

    The application of a computationally efficient kinematic control scheme for manipulators with redundant degrees of freedom to the unilateral telerobotic control of seven-degree-of-freedom manipulator (CESARM) at the Oak Ridge National Laboratory Center for Engineering Systems Advanced Research is presented. The kinematic control scheme uses a gradient projection optimization method, which eliminates that need to determine the generalized inverse of the Jacobian when solving for joint velocities, given Cartesian end-effector velocities. A six-degree-of-freedom (nonreplica) master controller is used. Performance indices for redundancy resolution are discussed. 5 ref., 6 figs.

  19. An optimal resolved rate law for kindematically redundant manipulators

    NASA Technical Reports Server (NTRS)

    Bourgeois, B. J.

    1987-01-01

    The resolved rate law for a manipulator provides the instantaneous joint rates required to satisfy a given instantaneous hand motion. When the joint space has more degrees of freedom than the task space, the manipulator is kinematically redundant and the kinematic rate equations are underdetermined. These equations can be locally optimized, but the resulting pseudo-inverse solution was found to cause large joint rates in some case. A weighting matrix in the locally optimized (pseudo-inverse) solution is dynamically adjusted to control the joint motion as desired. Joint reach limit avoidance is demonstrated in a kinematically redundant planar arm model. The treatment is applicable to redundant manipulators with any number of revolute joints and to nonplanar manipulators.

  20. Jerk-level synchronous repetitive motion scheme with gradient-type and zeroing-type dynamics algorithms applied to dual-arm redundant robot system control

    NASA Astrophysics Data System (ADS)

    Chen, Dechao; Zhang, Yunong

    2017-10-01

    Dual-arm redundant robot systems are usually required to handle primary tasks, repetitively and synchronously in practical applications. In this paper, a jerk-level synchronous repetitive motion scheme is proposed to remedy the joint-angle drift phenomenon and achieve the synchronous control of a dual-arm redundant robot system. The proposed scheme is novelly resolved at jerk level, which makes the joint variables, i.e. joint angles, joint velocities and joint accelerations, smooth and bounded. In addition, two types of dynamics algorithms, i.e. gradient-type (G-type) and zeroing-type (Z-type) dynamics algorithms, for the design of repetitive motion variable vectors, are presented in detail with the corresponding circuit schematics. Subsequently, the proposed scheme is reformulated as two dynamical quadratic programs (DQPs) and further integrated into a unified DQP (UDQP) for the synchronous control of a dual-arm robot system. The optimal solution of the UDQP is found by the piecewise-linear projection equation neural network. Moreover, simulations and comparisons based on a six-degrees-of-freedom planar dual-arm redundant robot system substantiate the operation effectiveness and tracking accuracy of the robot system with the proposed scheme for repetitive motion and synchronous control.

  1. ERK1 and ERK2 Map Kinases: Specific Roles or Functional Redundancy?

    PubMed Central

    Buscà, Roser; Pouysségur, Jacques; Lenormand, Philippe

    2016-01-01

    The MAP kinase signaling cascade Ras/Raf/MEK/ERK has been involved in a large variety of cellular and physiological processes that are crucial for life. Many pathological situations have been associated to this pathway. More than one isoform has been described at each level of the cascade. In this review we devoted our attention to ERK1 and ERK2, which are the effector kinases of the pathway. Whether ERK1 and ERK2 specify functional differences or are in contrast functionally redundant, constitutes an ongoing debate despite the huge amount of studies performed to date. In this review we compiled data on ERK1 vs. ERK2 gene structures, protein sequences, expression levels, structural and molecular mechanisms of activation and substrate recognition. We have also attempted to perform a rigorous analysis of studies regarding the individual roles of ERK1 and ERK2 by the means of morpholinos, siRNA, and shRNA silencing as well as gene disruption or gene replacement in mice. Finally, we comment on a recent study of gene and protein evolution of ERK isoforms as a distinct approach to address the same question. Our review permits the evaluation of the relevance of published studies in the field especially when measurements of global ERK activation are taken into account. Our analysis favors the hypothesis of ERK1 and ERK2 exhibiting functional redundancy and points to the concept of the global ERK quantity, and not isoform specificity, as being the essential determinant to achieve ERK function. PMID:27376062

  2. Asymmetric interjoint feedback contributes to postural control of redundant multi-link systems

    NASA Astrophysics Data System (ADS)

    Bunderson, Nathan E.; Ting, Lena H.; Burkholder, Thomas J.

    2007-09-01

    Maintaining the postural configuration of a limb such as an arm or leg is a fundamental neural control task that involves the coordination of multiple linked body segments. Biological systems are known to use a complex network of inter- and intra-joint feedback mechanisms arising from muscles, spinal reflexes and higher neuronal structures to stabilize the limbs. While previous work has shown that a small amount of asymmetric heterogenic feedback contributes to the behavior of these systems, a satisfactory functional explanation for this non-conservative feedback structure has not been put forth. We hypothesized that an asymmetric multi-joint control strategy would confer both an energetic and stability advantage in maintaining endpoint position of a kinematically redundant system. We tested this hypothesis by using optimal control models incorporating symmetric versus asymmetric feedback with the goal of maintaining the endpoint location of a kinematically redundant, planar limb. Asymmetric feedback improved endpoint control performance of the limb by 16%, reduced energetic cost by 21% and increased interjoint coordination by 40% compared to the symmetric feedback system. The overall effect of the asymmetry was that proximal joint motion resulted in greater torque generation at distal joints than vice versa. The asymmetric organization is consistent with heterogenic stretch reflex gains measured experimentally. We conclude that asymmetric feedback has a functionally relevant role in coordinating redundant degrees of freedom to maintain the position of the hand or foot.

  3. Asymmetric interjoint feedback contributes to postural control of redundant multi-link systems

    PubMed Central

    Bunderson, Nathan E.; Ting, Lena H.; Burkholder, Thomas J.

    2008-01-01

    Maintaining the postural configuration of a limb such as an arm or leg is a fundamental neural control task that involves the coordination of multiple linked body segments. Biological systems are known to use a complex network of inter- and intra-joint feedback mechanisms arising from muscles, spinal reflexes, and higher neuronal structures to stabilize the limbs. While previous work has shown that a small amount of asymmetric heterogenic feedback contributes to the behavior of these systems, a satisfactory functional explanation for this nonconservative feedback structure has not been put forth. We hypothesized that an asymmetric multi-joint control strategy would confer both an energetic and stability advantage in maintaining endpoint position of a kinematically redundant system. We tested this hypothesis by using optimal control models incorporating symmetric versus asymmetric feedback with the goal of maintaining the endpoint location of a kinematically redundant, planar limb. Asymmetric feedback improved endpoint control performance of the limb by 16%, reduced energetic cost by 21% and increased interjoint coordination by 40% compared to the symmetric feedback system. The overall effect of the asymmetry was that proximal joint motion resulted in greater torque generation at distal joints than vice versa. The asymmetric organization is consistent with heterogenic stretch reflex gains measured experimentally. We conclude that asymmetric feedback has a functionally relevant role in coordinating redundant degrees of freedom to maintain the position of the hand or foot. PMID:17873426

  4. Anti-backlash drive systems for multi-degree freedom devices

    DOEpatents

    Tsai, Lung-Wen; Chang, Sun-Lai

    1993-01-01

    A new and innovative concept for the control of backlash in gear-coupled transmission mechanisms. The concept utilizes redundant unidirectional drives to assure positive coupling of gear meshes at all times. Based on this concept, a methodology for the enumeration of admissible redundant-drive backlash-free robotic mechanisms has been established. Some typical two- and three-DOF mechanisms are disclosed. Furthermore, actuator torques have been derived as functions of either joint torques or end-effector dynamic performance requirements. A redundantly driven gear coupled transmission mechanism manipulator has a fail-safe advantage in that, except of the loss of backlash control, it can continue to function when one of its actuators fails. A two-DOF backlash-free arm has been reduced to practice to demonstrate the principle.

  5. Redundancy in electronic health record corpora: analysis, impact on text mining performance and mitigation strategies.

    PubMed

    Cohen, Raphael; Elhadad, Michael; Elhadad, Noémie

    2013-01-16

    The increasing availability of Electronic Health Record (EHR) data and specifically free-text patient notes presents opportunities for phenotype extraction. Text-mining methods in particular can help disease modeling by mapping named-entities mentions to terminologies and clustering semantically related terms. EHR corpora, however, exhibit specific statistical and linguistic characteristics when compared with corpora in the biomedical literature domain. We focus on copy-and-paste redundancy: clinicians typically copy and paste information from previous notes when documenting a current patient encounter. Thus, within a longitudinal patient record, one expects to observe heavy redundancy. In this paper, we ask three research questions: (i) How can redundancy be quantified in large-scale text corpora? (ii) Conventional wisdom is that larger corpora yield better results in text mining. But how does the observed EHR redundancy affect text mining? Does such redundancy introduce a bias that distorts learned models? Or does the redundancy introduce benefits by highlighting stable and important subsets of the corpus? (iii) How can one mitigate the impact of redundancy on text mining? We analyze a large-scale EHR corpus and quantify redundancy both in terms of word and semantic concept repetition. We observe redundancy levels of about 30% and non-standard distribution of both words and concepts. We measure the impact of redundancy on two standard text-mining applications: collocation identification and topic modeling. We compare the results of these methods on synthetic data with controlled levels of redundancy and observe significant performance variation. Finally, we compare two mitigation strategies to avoid redundancy-induced bias: (i) a baseline strategy, keeping only the last note for each patient in the corpus; (ii) removing redundant notes with an efficient fingerprinting-based algorithm. (a)For text mining, preprocessing the EHR corpus with fingerprinting yields significantly better results. Before applying text-mining techniques, one must pay careful attention to the structure of the analyzed corpora. While the importance of data cleaning has been known for low-level text characteristics (e.g., encoding and spelling), high-level and difficult-to-quantify corpus characteristics, such as naturally occurring redundancy, can also hurt text mining. Fingerprinting enables text-mining techniques to leverage available data in the EHR corpus, while avoiding the bias introduced by redundancy.

  6. Kinematics and control of redundant robotic arm based on dielectric elastomer actuators

    NASA Astrophysics Data System (ADS)

    Branz, Francesco; Antonello, Andrea; Carron, Andrea; Carli, Ruggero; Francesconi, Alessandro

    2015-04-01

    Soft robotics is a promising field and its application to space mechanisms could represent a breakthrough in space technologies by enabling new operative scenarios (e.g. soft manipulators, capture systems). Dielectric Elastomers Actuators have been under deep study for a number of years and have shown several advantages that could be of key importance for space applications. Among such advantages the most notable are high conversion efficiency, distributed actuation, self-sensing capability, multi-degree-of-freedom design, light weight and low cost. The big potentialities of double cone actuators have been proven in terms of good performances (i.e. stroke and force/torque), ease of manufacturing and durability. In this work the kinematic, dynamic and control design of a two-joint redundant robotic arm is presented. Two double cone actuators are assembled in series to form a two-link design. Each joint has two degrees of freedom (one rotational and one translational) for a total of four. The arm is designed to move in a 2-D environment (i.e. the horizontal plane) with 4 DoF, consequently having two degrees of redundancy. The redundancy is exploited in order to minimize the joint loads. The kinematic design with redundant Jacobian inversion is presented. The selected control algorithm is described along with the results of a number of dynamic simulations that have been executed for performance verification. Finally, an experimental setup is presented based on a flexible structure that counteracts gravity during testing in order to better emulate future zero-gravity applications.

  7. Intracellular metabolic pathway distribution in diatoms and tools for genome-enabled experimental diatom research.

    PubMed

    Gruber, Ansgar; Kroth, Peter G

    2017-09-05

    Diatoms are important primary producers in the oceans and can also dominate other aquatic habitats. One reason for the success of this phylogenetically relatively young group of unicellular organisms could be the impressive redundancy and diversity of metabolic isoenzymes in diatoms. This redundancy is a result of the evolutionary origin of diatom plastids by a eukaryote-eukaryote endosymbiosis, a process that implies temporary redundancy of functionally complete eukaryotic genomes. During the establishment of the plastids, this redundancy was partially reduced via gene losses, and was partially retained via gene transfer to the nucleus of the respective host cell. These gene transfers required re-assignment of intracellular targeting signals, a process that simultaneously altered the intracellular distribution of metabolic enzymes compared with the ancestral cells. Genome annotation, the correct assignment of the gene products and the prediction of putative function, strongly depends on the correct prediction of the intracellular targeting of a gene product. Here again diatoms are very peculiar, because the targeting systems for organelle import are partially different to those in land plants. In this review, we describe methods of predicting intracellular enzyme locations, highlight findings of metabolic peculiarities in diatoms and present genome-enabled approaches to study their metabolism.This article is part of the themed issue 'The peculiar carbon metabolism in diatoms'. © 2017 The Author(s).

  8. Drosophila Mitf regulates the V-ATPase and the lysosomal-autophagic pathway.

    PubMed

    Bouché, Valentina; Espinosa, Alma Perez; Leone, Luigi; Sardiello, Marco; Ballabio, Andrea; Botas, Juan

    2016-01-01

    An evolutionarily conserved gene network regulates the expression of genes involved in lysosome biogenesis, autophagy, and lipid metabolism. In mammals, TFEB and other members of the MiTF-TFE family of transcription factors control this network. Here we report that the lysosomal-autophagy pathway is controlled by Mitf gene in Drosophila melanogaster. Mitf is the single MiTF-TFE family member in Drosophila and prior to this work was known only for its function in eye development. We show that Mitf regulates the expression of genes encoding V-ATPase subunits as well as many additional genes involved in the lysosomal-autophagy pathway. Reduction of Mitf function leads to abnormal lysosomes and impairs autophagosome fusion and lipid breakdown during the response to starvation. In contrast, elevated Mitf levels increase the number of lysosomes, autophagosomes and autolysosomes, and decrease the size of lipid droplets. Inhibition of Drosophila MTORC1 induces Mitf translocation to the nucleus, underscoring conserved regulatory mechanisms between Drosophila and mammalian systems. Furthermore, we show Mitf-mediated clearance of cytosolic and nuclear expanded ATXN1 (ataxin 1) in a cellular model of spinocerebellar ataxia type 1 (SCA1). This remarkable observation illustrates the potential of the lysosomal-autophagy system to prevent toxic protein aggregation in both the cytoplasmic and nuclear compartments. We anticipate that the genetics of the Drosophila model and the absence of redundant MIT transcription factors will be exploited to investigate the regulation and function of the lysosomal-autophagy gene network.

  9. Commercialization of JPL Virtual Reality calibration and redundant manipulator control technologies

    NASA Technical Reports Server (NTRS)

    Kim, Won S.; Seraji, Homayoun; Fiorini, Paolo; Brown, Robert; Christensen, Brian; Beale, Chris; Karlen, James; Eismann, Paul

    1994-01-01

    Within NASA's recent thrust for industrial collaboration, JPL (Jet Propulsion Laboratory) has recently established two technology cooperation agreements in the robotics area: one on virtual reality (VR) calibration with Deneb Robotics, Inc., and the other on redundant manipulator control with Robotics Research Corporation (RRC). These technology transfer cooperation tasks will enable both Deneb and RRC to commercialize enhanced versions of their products that will greatly benefit both space and terrestrial telerobotic applications.

  10. Redundant and fault-tolerant algorithms for real-time measurement and control systems for weapon equipment.

    PubMed

    Li, Dan; Hu, Xiaoguang

    2017-03-01

    Because of the high availability requirements from weapon equipment, an in-depth study has been conducted on the real-time fault-tolerance of the widely applied Compact PCI (CPCI) bus measurement and control system. A redundancy design method that uses heartbeat detection to connect the primary and alternate devices has been developed. To address the low successful execution rate and relatively large waste of time slices in the primary version of the task software, an improved algorithm for real-time fault-tolerant scheduling is proposed based on the Basic Checking available time Elimination idle time (BCE) algorithm, applying a single-neuron self-adaptive proportion sum differential (PSD) controller. The experimental validation results indicate that this system has excellent redundancy and fault-tolerance, and the newly developed method can effectively improve the system availability. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  11. Ultrareliable fault-tolerant control systems

    NASA Technical Reports Server (NTRS)

    Webster, L. D.; Slykhouse, R. A.; Booth, L. A., Jr.; Carson, T. M.; Davis, G. J.; Howard, J. C.

    1984-01-01

    It is demonstrated that fault-tolerant computer systems, such as on the Shuttles, based on redundant, independent operation are a viable alternative in fault tolerant system designs. The ultrareliable fault-tolerant control system (UFTCS) was developed and tested in laboratory simulations of an UH-1H helicopter. UFTCS includes asymptotically stable independent control elements in a parallel, cross-linked system environment. Static redundancy provides the fault tolerance. A polling is performed among the computers, with results allowing for time-delay channel variations with tight bounds. When compared with the laboratory and actual flight data for the helicopter, the probability of a fault was, for the first 10 hr of flight given a quintuple computer redundancy, found to be 1 in 290 billion. Two weeks of untended Space Station operations would experience a fault probability of 1 in 24 million. Techniques for avoiding channel divergence problems are identified.

  12. Robotic control and inspection verification

    NASA Technical Reports Server (NTRS)

    Davis, Virgil Leon

    1991-01-01

    Three areas of possible commercialization involving robots at the Kennedy Space Center (KSC) are discussed: a six degree-of-freedom target tracking system for remote umbilical operations; an intelligent torque sensing end effector for operating hand valves in hazardous locations; and an automatic radiator inspection device, a 13 by 65 foot robotic mechanism involving completely redundant motors, drives, and controls. Aspects concerning the first two innovations can be integrated to enable robots or teleoperators to perform tasks involving orientation and panal actuation operations that can be done with existing technology rather than waiting for telerobots to incorporate artificial intelligence (AI) to perform 'smart' autonomous operations. The third robot involves the application of complete control hardware redundancy to enable performance of work over and near expensive Space Shuttle hardware. The consumer marketplace may wish to explore commercialization of similiar component redundancy techniques for applications when a robot would not normally be used because of reliability concerns.

  13. Expansion of banana (Musa acuminata) gene families involved in ethylene biosynthesis and signalling after lineage-specific whole-genome duplications.

    PubMed

    Jourda, Cyril; Cardi, Céline; Mbéguié-A-Mbéguié, Didier; Bocs, Stéphanie; Garsmeur, Olivier; D'Hont, Angélique; Yahiaoui, Nabila

    2014-05-01

    Whole-genome duplications (WGDs) are widespread in plants, and three lineage-specific WGDs occurred in the banana (Musa acuminata) genome. Here, we analysed the impact of WGDs on the evolution of banana gene families involved in ethylene biosynthesis and signalling, a key pathway for banana fruit ripening. Banana ethylene pathway genes were identified using comparative genomics approaches and their duplication modes and expression profiles were analysed. Seven out of 10 banana ethylene gene families evolved through WGD and four of them (1-aminocyclopropane-1-carboxylate synthase (ACS), ethylene-insensitive 3-like (EIL), ethylene-insensitive 3-binding F-box (EBF) and ethylene response factor (ERF)) were preferentially retained. Banana orthologues of AtEIN3 and AtEIL1, two major genes for ethylene signalling in Arabidopsis, were particularly expanded. This expansion was paralleled by that of EBF genes which are responsible for control of EIL protein levels. Gene expression profiles in banana fruits suggested functional redundancy for several MaEBF and MaEIL genes derived from WGD and subfunctionalization for some of them. We propose that EIL and EBF genes were co-retained after WGD in banana to maintain balanced control of EIL protein levels and thus avoid detrimental effects of constitutive ethylene signalling. In the course of evolution, subfunctionalization was favoured to promote finer control of ethylene signalling. © 2014 CIRAD New Phytologist © 2014 New Phytologist Trust.

  14. Robust adaptive kinematic control of redundant robots

    NASA Technical Reports Server (NTRS)

    Tarokh, M.; Zuck, D. D.

    1992-01-01

    The paper presents a general method for the resolution of redundancy that combines the Jacobian pseudoinverse and augmentation approaches. A direct adaptive control scheme is developed to generate joint angle trajectories for achieving desired end-effector motion as well as additional user defined tasks. The scheme ensures arbitrarily small errors between the desired and the actual motion of the manipulator. Explicit bounds on the errors are established that are directly related to the mismatch between actual and estimated pseudoinverse Jacobian matrix, motion velocity and the controller gain. It is shown that the scheme is tolerant of the mismatch and consequently only infrequent pseudoinverse computations are needed during a typical robot motion. As a result, the scheme is computationally fast, and can be implemented for real-time control of redundant robots. A method is incorporated to cope with the robot singularities allowing the manipulator to get very close or even pass through a singularity while maintaining a good tracking performance and acceptable joint velocities. Computer simulations and experimental results are provided in support of the theoretical developments.

  15. Distributed control topologies for deep space formation flying spacecraft

    NASA Technical Reports Server (NTRS)

    Hadaegh, F. Y.; Smith, R. S.

    2002-01-01

    A formation of satellites flying in deep space can be specified in terms of the relative satellite positions and absolute satellite orientations. The redundancy in the relative position specification generates a family of control topologies with equivalent stability and reference tracking performance, one of which can be implemented without requiring communication between the spacecraft. A relative position design formulation is inherently unobservable, and a methodology for circumventing this problem is presented. Additional redundancy in the control actuation space can be exploited for feed-forward control of the formation centroid's location in space, or for minimization of total fuel consumption.

  16. An optimal resolved rate law for kinematically redundant manipulators

    NASA Technical Reports Server (NTRS)

    Bourgeois, B. J.

    1987-01-01

    The resolved rate law for a manipulator provides the instantaneous joint rates required to satisfy a given instantaneous hand motion. When the joint space has more degrees of freedom than the task space, the manipulator is kinematically redundant and the kinematic rate equations are underdetermined. These equations can be locally optimized, but the resulting pseudo-inverse solution has been found to cause large joint rates in some cases. A weighting matrix in the locally optimized (pseudo-inverse) solution is dynamically adjusted to control the joint motion as desired. Joint reach limit avoidance is demonstrated in a kinematically redundant planar arm model. The treatment is applicable to redundant manipulators with any number of revolute joints and to non-planar manipulators.

  17. Analysis of a display and control system man-machine interface concept. Volume 1: Final technical report

    NASA Technical Reports Server (NTRS)

    Karl, D. R.

    1972-01-01

    An evaluation was made of the feasibility of utilizing a simplified man machine interface concept to manage and control a complex space system involving multiple redundant computers that control multiple redundant subsystems. The concept involves the use of a CRT for display and a simple keyboard for control, with a tree-type control logic for accessing and controlling mission, systems, and subsystem elements. The concept was evaluated in terms of the Phase B space shuttle orbiter, to utilize the wide scope of data management and subsystem control inherent in the central data management subsystem provided by the Phase B design philosophy. Results of these investigations are reported in four volumes.

  18. Intelligent failure-tolerant control

    NASA Technical Reports Server (NTRS)

    Stengel, Robert F.

    1991-01-01

    An overview of failure-tolerant control is presented, beginning with robust control, progressing through parallel and analytical redundancy, and ending with rule-based systems and artificial neural networks. By design or implementation, failure-tolerant control systems are 'intelligent' systems. All failure-tolerant systems require some degrees of robustness to protect against catastrophic failure; failure tolerance often can be improved by adaptivity in decision-making and control, as well as by redundancy in measurement and actuation. Reliability, maintainability, and survivability can be enhanced by failure tolerance, although each objective poses different goals for control system design. Artificial intelligence concepts are helpful for integrating and codifying failure-tolerant control systems, not as alternatives but as adjuncts to conventional design methods.

  19. Role of a new Rho family member in cell migration and axon guidance in C. elegans.

    PubMed

    Zipkin, I D; Kindt, R M; Kenyon, C J

    1997-09-05

    Rho family GTPases are thought to regulate actin-dependent processes, but their functions in vivo are still poorly understood. We have investigated the function of a new, widely expressed Rho family member in C. elegans by analyzing mutations in the endogenous gene. Activated and null alleles all inhibit cell migration, demonstrating that this protein is required for cell migration in vivo. Only a small subset of the migrations inhibited by activating mutations are inhibited by null mutations, suggesting that considerable functional redundancy exists within this system. Our findings support this conclusion and show that mig-2 functions redundantly with another pathway to regulate nuclear migration. Surprisingly, activated alleles also cause misguided axon growth, suggesting that Rho family GTPases may couple guidance cues to process outgrowth.

  20. Propulsion controls

    NASA Technical Reports Server (NTRS)

    Harkney, R. D.

    1980-01-01

    Increased system requirements and functional integration with the aircraft have placed an increased demand on control system capability and reliability. To provide these at an affordable cost and weight and because of the rapid advances in electronic technology, hydromechanical systems are being phased out in favor of digital electronic systems. The transition is expected to be orderly from electronic trimming of hydromechanical controls to full authority digital electronic control. Future propulsion system controls will be highly reliable full authority digital electronic with selected component and circuit redundancy to provide the required safety and reliability. Redundancy may include a complete backup control of a different technology for single engine applications. The propulsion control will be required to communicate rapidly with the various flight and fire control avionics as part of an integrated control concept.

  1. The Roles of NDR Protein Kinases in Hippo Signalling.

    PubMed

    Hergovich, Alexander

    2016-05-18

    The Hippo tumour suppressor pathway has emerged as a critical regulator of tissue growth through controlling cellular processes such as cell proliferation, death, differentiation and stemness. Traditionally, the core cassette of the Hippo pathway includes the MST1/2 protein kinases, the LATS1/2 protein kinases, and the MOB1 scaffold signal transducer, which together regulate the transcriptional co-activator functions of the proto-oncoproteins YAP and TAZ through LATS1/2-mediated phosphorylation of YAP/TAZ. Recent research has identified additional kinases, such as NDR1/2 (also known as STK38/STK38L) and MAP4Ks, which should be considered as novel members of the Hippo core cassette. While these efforts helped to expand our understanding of Hippo core signalling, they also began to provide insights into the complexity and redundancy of the Hippo signalling network. Here, we focus on summarising our current knowledge of the regulation and functions of mammalian NDR kinases, discussing parallels between the NDR pathways in Drosophila and mammals. Initially, we provide a general overview of the cellular functions of NDR kinases in cell cycle progression, centrosome biology, apoptosis, autophagy, DNA damage signalling, immunology and neurobiology. Finally, we put particular emphasis on discussing NDR1/2 as YAP kinases downstream of MST1/2 and MOB1 signalling in Hippo signalling.

  2. The secretory pathway: exploring yeast diversity.

    PubMed

    Delic, Marizela; Valli, Minoska; Graf, Alexandra B; Pfeffer, Martin; Mattanovich, Diethard; Gasser, Brigitte

    2013-11-01

    Protein secretion is an essential process for living organisms. In eukaryotes, this encompasses numerous steps mediated by several hundred cellular proteins. The core functions of translocation through the endoplasmic reticulum membrane, primary glycosylation, folding and quality control, and vesicle-mediated secretion are similar from yeasts to higher eukaryotes. However, recent research has revealed significant functional differences between yeasts and mammalian cells, and even among diverse yeast species. This review provides a current overview of the canonical protein secretion pathway in the model yeast Saccharomyces cerevisiae, highlighting differences to mammalian cells as well as currently unresolved questions, and provides a genomic comparison of the S. cerevisiae pathway to seven other yeast species where secretion has been investigated due to their attraction as protein production platforms, or for their relevance as pathogens. The analysis of Candida albicans, Candida glabrata, Kluyveromyces lactis, Pichia pastoris, Hansenula polymorpha, Yarrowia lipolytica, and Schizosaccharomyces pombe reveals that many - but not all - secretion steps are more redundant in S. cerevisiae due to duplicated genes, while some processes are even absent in this model yeast. Recent research obviates that even where homologous genes are present, small differences in protein sequence and/or differences in the regulation of gene expression may lead to quite different protein secretion phenotypes. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  3. Lockheed L-1101 avionic flight control redundant systems

    NASA Technical Reports Server (NTRS)

    Throndsen, E. O.

    1976-01-01

    The Lockheed L-1011 automatic flight control systems - yaw stability augmentation and automatic landing - are described in terms of their redundancies. The reliability objectives for these systems are discussed and related to in-service experience. In general, the availability of the stability augmentation system is higher than the original design requirement, but is commensurate with early estimates. The in-service experience with automatic landing is not sufficient to provide verification of Category 3 automatic landing system estimated availability.

  4. Analysis of expressed sequence tags from Actinidia: applications of a cross species EST database for gene discovery in the areas of flavor, health, color and ripening

    PubMed Central

    Crowhurst, Ross N; Gleave, Andrew P; MacRae, Elspeth A; Ampomah-Dwamena, Charles; Atkinson, Ross G; Beuning, Lesley L; Bulley, Sean M; Chagne, David; Marsh, Ken B; Matich, Adam J; Montefiori, Mirco; Newcomb, Richard D; Schaffer, Robert J; Usadel, Björn; Allan, Andrew C; Boldingh, Helen L; Bowen, Judith H; Davy, Marcus W; Eckloff, Rheinhart; Ferguson, A Ross; Fraser, Lena G; Gera, Emma; Hellens, Roger P; Janssen, Bart J; Klages, Karin; Lo, Kim R; MacDiarmid, Robin M; Nain, Bhawana; McNeilage, Mark A; Rassam, Maysoon; Richardson, Annette C; Rikkerink, Erik HA; Ross, Gavin S; Schröder, Roswitha; Snowden, Kimberley C; Souleyre, Edwige JF; Templeton, Matt D; Walton, Eric F; Wang, Daisy; Wang, Mindy Y; Wang, Yanming Y; Wood, Marion; Wu, Rongmei; Yauk, Yar-Khing; Laing, William A

    2008-01-01

    Background Kiwifruit (Actinidia spp.) are a relatively new, but economically important crop grown in many different parts of the world. Commercial success is driven by the development of new cultivars with novel consumer traits including flavor, appearance, healthful components and convenience. To increase our understanding of the genetic diversity and gene-based control of these key traits in Actinidia, we have produced a collection of 132,577 expressed sequence tags (ESTs). Results The ESTs were derived mainly from four Actinidia species (A. chinensis, A. deliciosa, A. arguta and A. eriantha) and fell into 41,858 non redundant clusters (18,070 tentative consensus sequences and 23,788 EST singletons). Analysis of flavor and fragrance-related gene families (acyltransferases and carboxylesterases) and pathways (terpenoid biosynthesis) is presented in comparison with a chemical analysis of the compounds present in Actinidia including esters, acids, alcohols and terpenes. ESTs are identified for most genes in color pathways controlling chlorophyll degradation and carotenoid biosynthesis. In the health area, data are presented on the ESTs involved in ascorbic acid and quinic acid biosynthesis showing not only that genes for many of the steps in these pathways are represented in the database, but that genes encoding some critical steps are absent. In the convenience area, genes related to different stages of fruit softening are identified. Conclusion This large EST resource will allow researchers to undertake the tremendous challenge of understanding the molecular basis of genetic diversity in the Actinidia genus as well as provide an EST resource for comparative fruit genomics. The various bioinformatics analyses we have undertaken demonstrates the extent of coverage of ESTs for genes encoding different biochemical pathways in Actinidia. PMID:18655731

  5. Anti-backlash drive systems for multi-degree freedom devices

    DOEpatents

    Lungwen Tsai; Sunlai Chang.

    1993-09-14

    A new and innovative concept is described for the control of backlash in gear-coupled transmission mechanisms. The concept utilizes redundant unidirectional drives to assure positive coupling of gear meshes at all times. Based on this concept, a methodology for the enumeration of admissible redundant-drive backlash-free robotic mechanisms has been established. Some typical two- and three-DOF mechanisms are disclosed. Furthermore, actuator torques have been derived as functions of either joint torques or end-effector dynamic performance requirements. A redundantly driven gear coupled transmission mechanism manipulator has a fail-safe advantage in that, except of the loss of backlash control, it can continue to function when one of its actuators fails. A two-DOF backlash-free arm has been reduced to practice to demonstrate the principle. 20 figures.

  6. Engineered bifunctional proteins and stem cells: next generation of targeted cancer therapeutics.

    PubMed

    Choi, Sung Hugh; Shah, Khalid

    2016-09-01

    Redundant survival signaling pathways and their crosstalk within tumor and/or between tumor and their microenvironment are key impediments to developing effective targeted therapies for cancer. Therefore developing therapeutics that target multiple receptor signaling pathways in tumors and utilizing efficient platforms to deliver such therapeutics are critical to the success of future targeted therapies. During the past two decades, a number of bifunctional multi-targeting antibodies, fusion proteins, and oncolytic viruses have been developed and various stem cell types have been engineered to efficiently deliver them to tumors. In this review, we discuss the design and efficacy of therapeutics targeting multiple pathways in tumors and the therapeutic potential of therapeutic stem cells engineered with bifunctional agents.

  7. Combining Best-Practice and Experimental Approaches: Redundancy, Images, and Misperceptions in Multimedia Learning

    ERIC Educational Resources Information Center

    Fenesi, Barbara; Heisz, Jennifer J.; Savage, Philip I.; Shore, David I.; Kim, Joseph A.

    2014-01-01

    This experiment combined controlled experimental design with a best-practice approach (i.e., real course content, subjective evaluations) to clarify the role of verbal redundancy, confirm the multimodal impact of images and narration, and highlight discrepancies between actual and perceived understanding. The authors presented 1 of 3…

  8. Complex Ancestries of Isoprenoid Synthesis in Dinoflagellates.

    PubMed

    Bentlage, Bastian; Rogers, Travis S; Bachvaroff, Tsvetan R; Delwiche, Charles F

    2016-01-01

    Isoprenoid metabolism occupies a central position in the anabolic metabolism of all living cells. In plastid-bearing organisms, two pathways may be present for de novo isoprenoid synthesis, the cytosolic mevalonate pathway (MVA) and nuclear-encoded, plastid-targeted nonmevalonate pathway (DOXP). Using transcriptomic data we find that dinoflagellates apparently make exclusive use of the DOXP pathway. Using phylogenetic analyses of all DOXP genes we inferred the evolutionary origins of DOXP genes in dinoflagellates. Plastid replacements led to a DOXP pathway of multiple evolutionary origins. Dinoflagellates commonly referred to as dinotoms due to their relatively recent acquisition of a diatom plastid, express two completely redundant DOXP pathways. Dinoflagellates with a tertiary plastid of haptophyte origin, by contrast, express a hybrid pathway of dual evolutionary origin. Here, changes in the targeting motif of signal/transit peptide likely allow for targeting the new plastid by the proteins of core isoprenoid metabolism proteins. Parasitic dinoflagellates of the Amoebophyra species complex appear to have lost the DOXP pathway, suggesting that they may rely on their host for sterol synthesis. © 2015 The Author(s) Journal of Eukaryotic Microbiology © 2015 International Society of Protistologists.

  9. Reflexive obstacle avoidance for kinematically-redundant manipulators

    NASA Technical Reports Server (NTRS)

    Karlen, James P.; Thompson, Jack M., Jr.; Farrell, James D.; Vold, Havard I.

    1989-01-01

    Dexterous telerobots incorporating 17 or more degrees of freedom operating under coordinated, sensor-driven computer control will play important roles in future space operations. They will also be used on Earth in assignments like fire fighting, construction and battlefield support. A real time, reflexive obstacle avoidance system, seen as a functional requirement for such massively redundant manipulators, was developed using arm-mounted proximity sensors to control manipulator pose. The project involved a review and analysis of alternative proximity sensor technologies for space applications, the development of a general-purpose algorithm for synthesizing sensor inputs, and the implementation of a prototypical system for demonstration and testing. A 7 degree of freedom Robotics Research K-2107HR manipulator was outfitted with ultrasonic proximity sensors as a testbed, and Robotics Research's standard redundant motion control algorithm was modified such that an object detected by sensor arrays located at the elbow effectively applies a force to the manipulator elbow, normal to the axis. The arm is repelled by objects detected by the sensors, causing the robot to steer around objects in the workspace automatically while continuing to move its tool along the commanded path without interruption. The mathematical approach formulated for synthesizing sensor inputs can be employed for redundant robots of any kinematic configuration.

  10. Functional Redundancy Between Canonical Endocannabinoid Signaling Systems in the Modulation of Anxiety.

    PubMed

    Bedse, Gaurav; Hartley, Nolan D; Neale, Emily; Gaulden, Andrew D; Patrick, Toni A; Kingsley, Philip J; Uddin, Md Jashim; Plath, Niels; Marnett, Lawrence J; Patel, Sachin

    2017-10-01

    Increasing the available repertoire of effective treatments for mood and anxiety disorders represents a critical unmet need. Pharmacological augmentation of endogenous cannabinoid (eCB) signaling has been suggested to represent a novel approach to the treatment of anxiety disorders; however, the functional interactions between two canonical eCB pathways mediated via anandamide (N-arachidonylethanolamine [AEA]) and 2-arachidonoylglycerol (2-AG) in the regulation of anxiety are not well understood. We utilized pharmacological augmentation and depletion combined with behavioral and electrophysiological approaches to probe the role of 2-AG signaling in the modulation of stress-induced anxiety and the functional redundancy between AEA and 2-AG signaling in the modulation of anxiety-like behaviors in mice. Selective 2-AG augmentation reduced anxiety in the light/dark box assay and prevented stress-induced increases in anxiety associated with limbic AEA deficiency. In contrast, acute 2-AG depletion increased anxiety-like behaviors, which was normalized by selective pharmacological augmentation of AEA signaling and via direct cannabinoid receptor 1 stimulation with Δ 9 -tetrahydrocannabinol. Electrophysiological studies revealed 2-AG modulation of amygdala glutamatergic transmission as a key synaptic correlate of the anxiolytic effects of 2-AG augmentation. Although AEA and 2-AG likely subserve distinct physiological roles, a pharmacological and functional redundancy between these canonical eCB signaling pathways exists in the modulation of anxiety-like behaviors. These data support development of eCB-based treatment approaches for mood and anxiety disorders and suggest a potentially wider therapeutic overlap between AEA and 2-AG augmentation approaches than was previously appreciated. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Dynamic modelling and estimation of the error due to asynchronism in a redundant asynchronous multiprocessor system

    NASA Technical Reports Server (NTRS)

    Huynh, Loc C.; Duval, R. W.

    1986-01-01

    The use of Redundant Asynchronous Multiprocessor System to achieve ultrareliable Fault Tolerant Control Systems shows great promise. The development has been hampered by the inability to determine whether differences in the outputs of redundant CPU's are due to failures or to accrued error built up by slight differences in CPU clock intervals. This study derives an analytical dynamic model of the difference between redundant CPU's due to differences in their clock intervals and uses this model with on-line parameter identification to idenitify the differences in the clock intervals. The ability of this methodology to accurately track errors due to asynchronisity generate an error signal with the effect of asynchronisity removed and this signal may be used to detect and isolate actual system failures.

  12. Modeling hormonal control of cambium proliferation.

    PubMed

    Oles, Vladyslav; Panchenko, Alexander; Smertenko, Andrei

    2017-01-01

    Rise of atmospheric CO2 is one of the main causes of global warming. Catastrophic climate change can be avoided by reducing emissions and increasing sequestration of CO2. Trees are known to sequester CO2 during photosynthesis, and then store it as wood biomass. Thus, breeding of trees with higher wood yield would mitigate global warming as well as augment production of renewable construction materials, energy, and industrial feedstock. Wood is made of cellulose-rich xylem cells produced through proliferation of a specialized stem cell niche called cambium. Importance of cambium in xylem cells production makes it an ideal target for the tree breeding programs; however our knowledge about control of cambium proliferation remains limited. The morphology and regulation of cambium are different from those of stem cell niches that control axial growth. For this reason, translating the knowledge about axial growth to radial growth has limited use. Furthermore, genetic approaches cannot be easily applied because overlaying tissues conceal cambium from direct observation and complicate identification of mutants. To overcome the paucity of experimental tools in cambium biology, we constructed a Boolean network CARENET (CAmbium REgulation gene NETwork) for modelling cambium activity, which includes the key transcription factors WOX4 and HD-ZIP III as well as their potential regulators. Our simulations predict that: (1) auxin, cytokinin, gibberellin, and brassinosteroids act cooperatively in promoting transcription of WOX4 and HD-ZIP III; (2) auxin and cytokinin pathways negatively regulate each other; (3) hormonal pathways act redundantly in sustaining cambium activity; (4) individual cambium cells can have diverse molecular identities. CARENET can be extended to include components of other signalling pathways and be integrated with models of xylem and phloem differentiation. Such extended models would facilitate breeding trees with higher wood yield.

  13. Task-space separation principle: a force-field approach to motion planning for redundant manipulators.

    PubMed

    Tommasino, Paolo; Campolo, Domenico

    2017-02-03

    In this work, we address human-like motor planning in redundant manipulators. Specifically, we want to capture postural synergies such as Donders' law, experimentally observed in humans during kinematically redundant tasks, and infer a minimal set of parameters to implement similar postural synergies in a kinematic model. For the model itself, although the focus of this paper is to solve redundancy by implementing postural strategies derived from experimental data, we also want to ensure that such postural control strategies do not interfere with other possible forms of motion control (in the task-space), i.e. solving the posture/movement problem. The redundancy problem is framed as a constrained optimization problem, traditionally solved via the method of Lagrange multipliers. The posture/movement problem can be tackled via the separation principle which, derived from experimental evidence, posits that the brain processes static torques (i.e. posture-dependent, such as gravitational torques) separately from dynamic torques (i.e. velocity-dependent). The separation principle has traditionally been applied at a joint torque level. Our main contribution is to apply the separation principle to Lagrange multipliers, which act as task-space force fields, leading to a task-space separation principle. In this way, we can separate postural control (implementing Donders' law) from various types of tasks-space movement planners. As an example, the proposed framework is applied to the (redundant) task of pointing with the human wrist. Nonlinear inverse optimization (NIO) is used to fit the model parameters and to capture motor strategies displayed by six human subjects during pointing tasks. The novelty of our NIO approach is that (i) the fitted motor strategy, rather than raw data, is used to filter and down-sample human behaviours; (ii) our framework is used to efficiently simulate model behaviour iteratively, until it converges towards the experimental human strategies.

  14. A general framework for the manual teleoperation of kinematically redundant space-based manipulators

    NASA Astrophysics Data System (ADS)

    Dupuis, Erick

    This thesis provides a general framework for the manual teleoperation of kinematically redundant space-based manipulators. It is proposed to break down the task of controlling the motion of a redundant manipulator into a sequence of manageable sub-tasks of lower dimension by imposing constraints on the motion of intermediate bodies of the manipulator. This implies that the manipulator then becomes a non-redundant kinematic chain and the operator only controls a reduced number of degrees of freedom at any time. However, by appropriately changing the imposed constraints, the operator can use the full capability of the manipulator throughout the task. Also, by not restricting the point of teleoperation to the end effector but effectively allowing direct control of intermediate bodies of the robot, it is possible to teleoperate a redundant robot of arbitrary kinematic architecture over its entire configuration space in a predictable and natural fashion. It is rigourously proven that this approach will always work for any kinematically redundant serial manipulator regardless of its topology, geometry and of the number of its excess degrees-of-freedom. Furthermore, a methodology is provided for the selection of task and constraint coordinates to ensure the absence of algorithmic rank-deficiencies. Two novel algorithms are provided for the symbolic determination of the rank-deficiency locus of rectangular Jacobian matrices: the Singular Vector Algorithm and the Recursive Sub-Determinant Algorithm. These algorithms are complementary to each other: the former being more computationally efficient and the latter more robust. The application of the methodology to sample cases of varying complexity has demonstrated its power and limitations: It has been shown to be powerful enough to generate complete sets of task/constraint coordinate pairs for realistic examples such as the Space Station Remote Manipulator System and a simplified version of the Special Purpose Dexterous Manipulator.

  15. Electromechanical actuation for cryogenic valve control

    NASA Technical Reports Server (NTRS)

    Lister, M. J.; Reichmuth, D. M.

    1993-01-01

    The design and analysis of the electromechanical actuator (EMA) being developed for the NASA/Marshall Space Flight Center as part of the National Launch System (NLS) Propellant Control Effector Advanced Development Program (ADP) are addressed. The EMA design uses several proven technologies combined into a single modular package which includes single stage high ratio gear reduction, redundant electric motors mounted on a common drive shaft, redundant drive and control electronics, and digital technology for performing the closed loop position feedback, communication, and health monitoring functions. Results of tests aimed at evaluating both component characteristics and overall system performance demonstrated that the goal of low cost, reliable control in a cryogenic environment is feasible.

  16. Coordinated Control Of Mobile Robotic Manipulators

    NASA Technical Reports Server (NTRS)

    Seraji, Homayoun

    1995-01-01

    Computationally efficient scheme developed for on-line coordinated control of both manipulation and mobility of robots that include manipulator arms mounted on mobile bases. Applicable to variety of mobile robotic manipulators, including robots that move along tracks (typically, painting and welding robots), robots mounted on gantries and capable of moving in all three dimensions, wheeled robots, and compound robots (consisting of robots mounted on other robots). Theoretical basis discussed in several prior articles in NASA Tech Briefs, including "Increasing the Dexterity of Redundant Robots" (NPO-17801), "Redundant Robot Can Avoid Obstacles" (NPO-17852), "Configuration-Control Scheme Copes With Singularities" (NPO-18556), "More Uses for Configuration Control of Robots" (NPO-18607/NPO-18608).

  17. Modeling the Fault Tolerant Capability of a Flight Control System: An Exercise in SCR Specification

    NASA Technical Reports Server (NTRS)

    Alexander, Chris; Cortellessa, Vittorio; DelGobbo, Diego; Mili, Ali; Napolitano, Marcello

    2000-01-01

    In life-critical and mission-critical applications, it is important to make provisions for a wide range of contingencies, by providing means for fault tolerance. In this paper, we discuss the specification of a flight control system that is fault tolerant with respect to sensor faults. Redundancy is provided by analytical relations that hold between sensor readings; depending on the conditions, this redundancy can be used to detect, identify and accommodate sensor faults.

  18. Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells.

    PubMed

    Fletcher, Rachel S; Ratajczak, Joanna; Doig, Craig L; Oakey, Lucy A; Callingham, Rebecca; Da Silva Xavier, Gabriella; Garten, Antje; Elhassan, Yasir S; Redpath, Philip; Migaud, Marie E; Philp, Andrew; Brenner, Charles; Canto, Carles; Lavery, Gareth G

    2017-08-01

    Augmenting nicotinamide adenine dinucleotide (NAD + ) availability may protect skeletal muscle from age-related metabolic decline. Dietary supplementation of NAD + precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) appear efficacious in elevating muscle NAD + . Here we sought to identify the pathways skeletal muscle cells utilize to synthesize NAD + from NMN and NR and provide insight into mechanisms of muscle metabolic homeostasis. We exploited expression profiling of muscle NAD + biosynthetic pathways, single and double nicotinamide riboside kinase 1/2 (NRK1/2) loss-of-function mice, and pharmacological inhibition of muscle NAD + recycling to evaluate NMN and NR utilization. Skeletal muscle cells primarily rely on nicotinamide phosphoribosyltransferase (NAMPT), NRK1, and NRK2 for salvage biosynthesis of NAD + . NAMPT inhibition depletes muscle NAD + availability and can be rescued by NR and NMN as the preferred precursors for elevating muscle cell NAD + in a pathway that depends on NRK1 and NRK2. Nrk2 knockout mice develop normally and show subtle alterations to their NAD+ metabolome and expression of related genes. NRK1, NRK2, and double KO myotubes revealed redundancy in the NRK dependent metabolism of NR to NAD + . Significantly, these models revealed that NMN supplementation is also dependent upon NRK activity to enhance NAD + availability. These results identify skeletal muscle cells as requiring NAMPT to maintain NAD + availability and reveal that NRK1 and 2 display overlapping function in salvage of exogenous NR and NMN to augment intracellular NAD + availability.

  19. Modeling and Control of the Redundant Parallel Adjustment Mechanism on a Deployable Antenna Panel

    PubMed Central

    Tian, Lili; Bao, Hong; Wang, Meng; Duan, Xuechao

    2016-01-01

    With the aim of developing multiple input and multiple output (MIMO) coupling systems with a redundant parallel adjustment mechanism on the deployable antenna panel, a structural control integrated design methodology is proposed in this paper. Firstly, the modal information from the finite element model of the structure of the antenna panel is extracted, and then the mathematical model is established with the Hamilton principle; Secondly, the discrete Linear Quadratic Regulator (LQR) controller is added to the model in order to control the actuators and adjust the shape of the panel. Finally, the engineering practicality of the modeling and control method based on finite element analysis simulation is verified. PMID:27706076

  20. Decentralized control

    NASA Technical Reports Server (NTRS)

    Steffen, Chris

    1990-01-01

    An overview of the time-delay problem and the reliability problem which arise in trying to perform robotic construction operations at a remote space location are presented. The effects of the time-delay upon the control system design will be itemized. A high level overview of a decentralized method of control which is expected to perform better than the centralized approach in solving the time-delay problem is given. The lower level, decentralized, autonomous, Troter Move-Bar algorithm is also presented (Troters are coordinated independent robots). The solution of the reliability problem is connected to adding redundancy to the system. One method of adding redundancy is given.

  1. Description of a dual fail-operational redundant strapdown inertial measurement unit for integrated avionics systems research

    NASA Technical Reports Server (NTRS)

    Bryant, W. H.; Morrell, F. R.

    1981-01-01

    Attention is given to a redundant strapdown inertial measurement unit for integrated avionics. The system consists of four two-degree-of-freedom turned rotor gyros and four two-degree-of-freedom accelerometers in a skewed and separable semi-octahedral array. The unit is coupled through instrument electronics to two flight computers which compensate sensor errors. The flight computers are interfaced to the microprocessors and process failure detection, isolation, redundancy management and flight control/navigation algorithms. The unit provides dual fail-operational performance and has data processing frequencies consistent with integrated avionics concepts presently planned.

  2. Capillary response to skeletal muscle contraction: evidence that redundancy between vasodilators is physiologically relevant during active hyperaemia.

    PubMed

    Lamb, Iain R; Novielli, Nicole M; Murrant, Coral L

    2018-04-15

    The current theory behind matching blood flow to metabolic demand of skeletal muscle suggests redundant interactions between metabolic vasodilators. Capillaries play an important role in blood flow control given their ability to respond to muscle contraction by causing conducted vasodilatation in upstream arterioles that control their perfusion. We sought to determine whether redundancies occur between vasodilators at the level of the capillary by stimulating the capillaries with muscle contraction and vasodilators relevant to muscle contraction. We identified redundancies between potassium and both adenosine and nitric oxide, between nitric oxide and potassium, and between adenosine and both potassium and nitric oxide. During muscle contraction, we demonstrate redundancies between potassium and nitric oxide as well as between potassium and adenosine. Our data show that redundancy is physiologically relevant and involved in the coordination of the vasodilator response during muscle contraction at the level of the capillaries. We sought to determine if redundancy between vasodilators is physiologically relevant during active hyperaemia. As inhibitory interactions between vasodilators are indicative of redundancy, we tested whether vasodilators implicated in mediating active hyperaemia (potassium (K + ), adenosine (ADO) and nitric oxide (NO)) inhibit one another's vasodilatory effects through direct application of pharmacological agents and during muscle contraction. Using the hamster cremaster muscle and intravital microscopy, we locally stimulated capillaries with one vasodilator in the absence and the presence of a second vasodilator (10 -7 m S-nitroso-N-acetylpenicillamine (SNAP), 10 -7 m ADO, 10 mm KCl) applied sequentially and simultaneously, and observed the response in the associated upstream 4A arteriole controlling the perfusion of the stimulated capillary. We found that KCl significantly attenuated SNAP- and ADO-induced vasodilatations by ∼49.7% and ∼128.0% respectively and ADO significantly attenuated KCl- and SNAP-induced vasodilatations by ∼94.7% and ∼59.6%, respectively. NO significantly attenuated KCl vasodilatation by 93.8%. Further, during muscle contraction we found that inhibition of NO production using l-N G -nitroarginine methyl ester and inhibition of ADO receptors using xanthine amine congener was effective at inhibiting contraction-induced vasodilatation but only in the presence of K + release channel inhibition. Thus, only when the inhibiting vasodilator K + was blocked was the second vasodilator, NO or ADO, able to produce effective vasodilatation. Therefore, we show that there are inhibitory interactions between specific vasodilators at the level of the capillary. Further, these inhibitions can be observed during muscle contraction indicating that redundancies between vasodilators are physiologically relevant and influence vasodilatation during active hyperaemia. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

  3. “Redundancy” of Endocannabinoid Inactivation: New Challenges and Opportunities for Pain Control

    PubMed Central

    2012-01-01

    Redundancy of metabolic pathways and molecular targets is a typical feature of all lipid mediators, and endocannabinoids, which were originally defined as endogenous agonists at cannabinoid CB1 and CB2 receptors, are no exception. In particular, the two most studied endocannabinoids, anandamide and 2-arachidonoylglycerol, are inactivated through alternative biochemical routes, including hydrolysis and oxidation, and more than one enzyme might be used even for the same type of inactivating reaction. These enzymes also recognize as substrates other concurrent lipid mediators, whereas, in turn, endocannabinoids might interact with noncannabinoid receptors with subcellular distribution and ultimate biological actions either similar to or completely different from those of cannabinoid receptors. Even splicing variants of endocannabinoid hydrolyzing enzymes, such as FAAH-1, might play distinct roles in endocannabinoid inactivation. Finally, the products of endocannabinoid catabolism may have their own targets, with biological roles different from those of cannabinoid receptors. These peculiarities of endocannabinoid signaling have complicated the use of inhibitors of its inactivation mechanisms as a safer and more efficacious alternative to the direct targeting of cannabinoid receptors for the treatment of several pathological conditions, including pain. However, new strategies, including the rediscovery of “dirty drugs”, and the use of certain natural products (including non-THC cannabis constituents), are emerging that might allow us to make a virtue of necessity and exploit endocannabinoid redundancy to develop new analgesics. PMID:22860203

  4. Redundancy reduction explains the expansion of visual direction space around the cardinal axes.

    PubMed

    Perrone, John A; Liston, Dorion B

    2015-06-01

    Motion direction discrimination in humans is worse for oblique directions than for the cardinal directions (the oblique effect). For some unknown reason, the human visual system makes systematic errors in the estimation of particular motion directions; a direction displacement near a cardinal axis appears larger than it really is whereas the same displacement near an oblique axis appears to be smaller. Although the perceptual effects are robust and are clearly measurable in smooth pursuit eye movements, all attempts to identify the neural underpinnings for the oblique effect have failed. Here we show that a model of image velocity estimation based on the known properties of neurons in primary visual cortex (V1) and the middle temporal (MT) visual area of the primate brain produces the oblique effect. We also provide an explanation for the unusual asymmetric patterns of inhibition that have been found surrounding MT neurons. These patterns are consistent with a mechanism within the visual system that prevents redundant velocity signals from being passed onto the next motion-integration stage, (dorsal Medial superior temporal, MSTd). We show that model redundancy-reduction mechanisms within the MT-MSTd pathway produce the oblique effect. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Two redundant octanoyltransferases and one obligatory lipoyl synthase provide protein-lipoylation autonomy to plastids of Arabidopsis.

    PubMed

    Ewald, R; Hoffmann, C; Neuhaus, E; Bauwe, H

    2014-01-01

    Octanoyltransferases (LIP2) are important for the lipoylation of several α-ketoacid decarboxylases and glycine decarboxylase, all of which are essential multienzyme complexes of central metabolism, by attaching de novo-synthesised octanoyl moieties to the respective target subunits. Lipoyl synthase (LIP1) then inserts two sulphur atoms each into the protein-bound octanoyl chains to generate the functional lipoamide arms. In plants, most of the above multienzyme complexes occur only in mitochondria. Pyruvate dehydrogenase is an exception, since it also occurs in plastids. Plastidial LIP1 and LIP2 are known, but it is not clear how essential these enzymes are. Here, we report that not just one but two redundant LIP2 isoforms, LIP2p and LIP2p2, operate in plastids of Arabidopsis. The combined deletion of the two isoenzymes is embryo-lethal. Deletion of the plastidial lipoyl synthase LIP1p is also embryo-lethal, indicating that all plastidial LIP1 activity is due to LIP1p. These features suggest that protein lipoylation is based on an autonomous and partially redundant de novo lipoylation pathway in plastids. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

  6. Environmental Support Hypothesis in Designing Multimedia Training for Older Adults: Is Less Always More?

    ERIC Educational Resources Information Center

    Pachman, Mariya; Ke, Fengfeng

    2012-01-01

    This study explores younger and older adults learning of MS Publisher functionalities from a multimedia tutorial. Twenty younger and twenty three older adults assigned to a redundant (experimental) or non-redundant (control) condition were taught how to create a greeting card, while the results of their learning were assessed with immediate and…

  7. Dataflow models for fault-tolerant control systems

    NASA Technical Reports Server (NTRS)

    Papadopoulos, G. M.

    1984-01-01

    Dataflow concepts are used to generate a unified hardware/software model of redundant physical systems which are prone to faults. Basic results in input congruence and synchronization are shown to reduce to a simple model of data exchanges between processing sites. Procedures are given for the construction of congruence schemata, the distinguishing features of any correctly designed redundant system.

  8. Regulatory logic of pan-neuronal gene expression in C. elegans

    PubMed Central

    Stefanakis, Nikolaos; Carrera, Ines; Hobert, Oliver

    2015-01-01

    While neuronal cell types display an astounding degree of phenotypic diversity, most if not all neuron types share a core panel of terminal features. However, little is known about how pan-neuronal expression patterns are genetically programmed. Through an extensive analysis of the cis-regulatory control regions of a battery of pan-neuronal C.elegans genes, including genes involved in synaptic vesicle biology and neuropeptide signaling, we define a common organizational principle in the regulation of pan-neuronal genes in the form of a surprisingly complex array of seemingly redundant, parallel-acting cis-regulatory modules that direct expression to broad, overlapping domains throughout the nervous system. These parallel-acting cis-regulatory modules are responsive to a multitude of distinct trans-acting factors. Neuronal gene expression programs therefore fall into two fundamentally distinct classes. Neuron type-specific genes are generally controlled by discrete and non-redundantly acting regulatory inputs, while pan-neuronal gene expression is controlled by diverse, coincident and seemingly redundant regulatory inputs. PMID:26291158

  9. Kinematically Optimal Robust Control of Redundant Manipulators

    NASA Astrophysics Data System (ADS)

    Galicki, M.

    2017-12-01

    This work deals with the problem of the robust optimal task space trajectory tracking subject to finite-time convergence. Kinematic and dynamic equations of a redundant manipulator are assumed to be uncertain. Moreover, globally unbounded disturbances are allowed to act on the manipulator when tracking the trajectory by the endeffector. Furthermore, the movement is to be accomplished in such a way as to minimize both the manipulator torques and their oscillations thus eliminating the potential robot vibrations. Based on suitably defined task space non-singular terminal sliding vector variable and the Lyapunov stability theory, we derive a class of chattering-free robust kinematically optimal controllers, based on the estimation of transpose Jacobian, which seem to be effective in counteracting both uncertain kinematics and dynamics, unbounded disturbances and (possible) kinematic and/or algorithmic singularities met on the robot trajectory. The numerical simulations carried out for a redundant manipulator of a SCARA type consisting of the three revolute kinematic pairs and operating in a two-dimensional task space, illustrate performance of the proposed controllers as well as comparisons with other well known control schemes.

  10. Spatial Phosphoprotein Profiling Reveals a Compartmentalized Extracellular Signal-regulated Kinase Switch Governing Neurite Growth and Retraction

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

    Wang, Yingchun; Yang, Feng; Fu, Yi

    Abstract - Brain development and spinal cord regeneration require neurite sprouting and growth cone navigation in response to extension and collapsing factors present in the extracellular environment. These external guidance cues control neurite growth cone extension and retraction processes through intracellular protein phosphorylation of numerous cytoskeletal, adhesion, and polarity complex signaling proteins. However, the complex kinase/substrate signaling networks that mediate neuritogenesis have not been investigated. Here, we compare the neurite phosphoproteome under growth and retraction conditions using neurite purification methodology combined with mass spectrometry. More than 4000 non-redundant phosphorylation sites from 1883 proteins have been annotated and mapped to signalingmore » pathways that control kinase/phosphatase networks, cytoskeleton remodeling, and axon/dendrite specification. Comprehensive informatics and functional studies revealed a compartmentalized ERK activation/deactivation cytoskeletal switch that governs neurite growth and retraction, respectively. Our findings provide the first system-wide analysis of the phosphoprotein signaling networks that enable neurite growth and retraction and reveal an important molecular switch that governs neuritogenesis.« less

  11. Economical analysis of saturation mutagenesis experiments

    PubMed Central

    Acevedo-Rocha, Carlos G.; Reetz, Manfred T.; Nov, Yuval

    2015-01-01

    Saturation mutagenesis is a powerful technique for engineering proteins, metabolic pathways and genomes. In spite of its numerous applications, creating high-quality saturation mutagenesis libraries remains a challenge, as various experimental parameters influence in a complex manner the resulting diversity. We explore from the economical perspective various aspects of saturation mutagenesis library preparation: We introduce a cheaper and faster control for assessing library quality based on liquid media; analyze the role of primer purity and supplier in libraries with and without redundancy; compare library quality, yield, randomization efficiency, and annealing bias using traditional and emergent randomization schemes based on mixtures of mutagenic primers; and establish a methodology for choosing the most cost-effective randomization scheme given the screening costs and other experimental parameters. We show that by carefully considering these parameters, laboratory expenses can be significantly reduced. PMID:26190439

  12. Controllability of control and mixture weakly dependent siphons in S3PR

    NASA Astrophysics Data System (ADS)

    Hong, Liang; Chao, Daniel Y.

    2013-08-01

    Deadlocks in a flexible manufacturing system modelled by Petri nets arise from insufficiently marked siphons. Monitors are added to control these siphons to avoid deadlocks rendering the system too complicated since the total number of monitors grows exponentially. Li and Zhou propose to add monitors only to elementary siphons while controlling the other (strongly or weakly) dependent siphons by adjusting control depth variables. To avoid generating new siphons, the control arcs are ended at source transitions of process nets. This disturbs the original model more and hence loses more live states. Negative terms in the controllability make the control policy for weakly dependent siphons rather conservative. We studied earlier on the controllability of strongly dependent siphons and proposed to add monitors in the order of basic, compound, control, partial mixture and full mixture (strongly dependent) siphons to reduce the number of mixed integer programming iterations and redundant monitors. This article further investigates the controllability of siphons derived from weakly 2-compound siphons. We discover that the controllability for weakly and strongly compound siphons is similar. It no longer holds for control and mixture siphons. Some control and mixture siphons, derived from strongly 2-compound siphons are not redundant - no longer so for those derived from weakly 2-compound siphons; that is all control and mixture siphons are redundant. They do not need to be the conservative one as proposed by Li and Zhou. Thus, we can adopt the maximally permissive control policy even though new siphons are generated.

  13. Flight experience with flight control redundancy management

    NASA Technical Reports Server (NTRS)

    Szalai, K. J.; Larson, R. R.; Glover, R. D.

    1980-01-01

    Flight experience with both current and advanced redundancy management schemes was gained in recent flight research programs using the F-8 digital fly by wire aircraft. The flight performance of fault detection, isolation, and reconfiguration (FDIR) methods for sensors, computers, and actuators is reviewed. Results of induced failures as well as of actual random failures are discussed. Deficiencies in modeling and implementation techniques are also discussed. The paper also presents comparison off multisensor tracking in smooth air, in turbulence, during large maneuvers, and during maneuvers typical of those of large commercial transport aircraft. The results of flight tests of an advanced analytic redundancy management algorithm are compared with the performance of a contemporary algorithm in terms of time to detection, false alarms, and missed alarms. The performance of computer redundancy management in both iron bird and flight tests is also presented.

  14. Comparative transcriptomics reveals genes involved in metabolic and immune pathways in the digestive gland of scallop Chlamys farreri following cadmium exposure

    NASA Astrophysics Data System (ADS)

    Zhang, Hui; Zhai, Yuxiu; Yao, Lin; Jiang, Yanhua; Li, Fengling

    2017-05-01

    Chlamys farreri is an economically important mollusk that can accumulate excessive amounts of cadmium (Cd). Studying the molecular mechanism of Cd accumulation in bivalves is difficult because of the lack of genome background. Transcriptomic analysis based on high-throughput RNA sequencing has been shown to be an efficient and powerful method for the discovery of relevant genes in non-model and genome reference-free organisms. Here, we constructed two cDNA libraries (control and Cd exposure groups) from the digestive gland of C. farreri and compared the transcriptomic data between them. A total of 227 673 transcripts were assembled into 105 071 unigenes, most of which shared high similarity with sequences in the NCBI non-redundant protein database. For functional classification, 24 493 unigenes were assigned to Gene Ontology terms. Additionally, EuKaryotic Ortholog Groups and Kyoto Encyclopedia of Genes and Genomes analyses assigned 12 028 unigenes to 26 categories and 7 849 unigenes to five pathways, respectively. Comparative transcriptomics analysis identified 3 800 unigenes that were differentially expressed in the Cd-treated group compared with the control group. Among them, genes associated with heavy metal accumulation were screened, including metallothionein, divalent metal transporter, and metal tolerance protein. The functional genes and predicted pathways identified in our study will contribute to a better understanding of the metabolic and immune system in the digestive gland of C. farreri. In addition, the transcriptomic data will provide a comprehensive resource that may contribute to the understanding of molecular mechanisms that respond to marine pollutants in bivalves.

  15. Cancer cachexia: mediators, signaling, and metabolic pathways.

    PubMed

    Fearon, Kenneth C H; Glass, David J; Guttridge, Denis C

    2012-08-08

    Cancer cachexia is characterized by a significant reduction in body weight resulting predominantly from loss of adipose tissue and skeletal muscle. Cachexia causes reduced cancer treatment tolerance and reduced quality and length of life, and remains an unmet medical need. Therapeutic progress has been impeded, in part, by the marked heterogeneity of mediators, signaling, and metabolic pathways both within and between model systems and the clinical syndrome. Recent progress in understanding conserved, molecular mechanisms of skeletal muscle atrophy/hypertrophy has provided a downstream platform for circumventing the variations and redundancy in upstream mediators and may ultimately translate into new targeted therapies. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. An Autonomous Flight Safety System

    DTIC Science & Technology

    2008-11-01

    are taken. AFSS can take vehicle navigation data from redundant onboard sensors and make flight termination decisions using software-based rules...implemented on redundant flight processors. By basing these decisions on actual Instantaneous Impact Predictions and by providing for an arbitrary...number of mission rules, it is the contention of the AFSS development team that the decision making process used by Missile Flight Control Officers

  17. Formal design and verification of a reliable computing platform for real-time control. Phase 2: Results

    NASA Technical Reports Server (NTRS)

    Butler, Ricky W.; Divito, Ben L.

    1992-01-01

    The design and formal verification of the Reliable Computing Platform (RCP), a fault tolerant computing system for digital flight control applications is presented. The RCP uses N-Multiply Redundant (NMR) style redundancy to mask faults and internal majority voting to flush the effects of transient faults. The system is formally specified and verified using the Ehdm verification system. A major goal of this work is to provide the system with significant capability to withstand the effects of High Intensity Radiated Fields (HIRF).

  18. Description of a dual fail operational redundant strapdown inertial measurement unit for integrated avionics systems research

    NASA Technical Reports Server (NTRS)

    Bryant, W. H.; Morrell, F. R.

    1981-01-01

    An experimental redundant strapdown inertial measurement unit (RSDIMU) is developed as a link to satisfy safety and reliability considerations in the integrated avionics concept. The unit includes four two degree-of-freedom tuned rotor gyros, and four accelerometers in a skewed and separable semioctahedral array. These sensors are coupled to four microprocessors which compensate sensor errors. These microprocessors are interfaced with two flight computers which process failure detection, isolation, redundancy management, and general flight control/navigation algorithms. Since the RSDIMU is a developmental unit, it is imperative that the flight computers provide special visibility and facility in algorithm modification.

  19. Redundancy management of electrohydraulic servoactuators by mathematical model referencing

    NASA Technical Reports Server (NTRS)

    Campbell, R. A.

    1971-01-01

    A description of a mathematical model reference system is presented which provides redundancy management for an electrohydraulic servoactuator. The mathematical model includes a compensation network that calculates reference parameter perturbations induced by external disturbance forces. This is accomplished by using the measured pressure differential data taken from the physical system. This technique was experimentally verified by tests performed using the H-1 engine thrust vector control system for Saturn IB. The results of these tests are included in this report. It was concluded that this technique improves the tracking accuracy of the model reference system to the extent that redundancy management of electrohydraulic servosystems may be performed using this method.

  20. Sugar - hormone crosstalk in seed development: Two redundant pathways of IAA biosynthesis are regulated differentially in the invertase-deficient miniature1 (mn1) seed mutant in maize

    USDA-ARS?s Scientific Manuscript database

    The miniature1 (mn1) seed phenotype is a loss-of-function mutation at the Mn1 locus that encodes a cell wall invertase; its deficiency leads to pleiotropic changes including altered sugar levels and decreased levels of IAA throughout seed development. To understand the molecular details of such suga...

  1. The Case for Modular Redundancy in Large-Scale High Performance Computing Systems

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

    Engelmann, Christian; Ong, Hong Hoe; Scott, Stephen L

    2009-01-01

    Recent investigations into resilience of large-scale high-performance computing (HPC) systems showed a continuous trend of decreasing reliability and availability. Newly installed systems have a lower mean-time to failure (MTTF) and a higher mean-time to recover (MTTR) than their predecessors. Modular redundancy is being used in many mission critical systems today to provide for resilience, such as for aerospace and command \\& control systems. The primary argument against modular redundancy for resilience in HPC has always been that the capability of a HPC system, and respective return on investment, would be significantly reduced. We argue that modular redundancy can significantly increasemore » compute node availability as it removes the impact of scale from single compute node MTTR. We further argue that single compute nodes can be much less reliable, and therefore less expensive, and still be highly available, if their MTTR/MTTF ratio is maintained.« less

  2. Atkinesin-13A Modulates Cell-Wall Synthesis and Cell Expansion in Arabidopsis thaliana via the THESEUS1 Pathway

    PubMed Central

    Fujikura, Ushio; Elsaesser, Lore; Breuninger, Holger; Sánchez-Rodríguez, Clara; Ivakov, Alexander; Laux, Thomas; Findlay, Kim; Persson, Staffan; Lenhard, Michael

    2014-01-01

    Growth of plant organs relies on cell proliferation and expansion. While an increasingly detailed picture about the control of cell proliferation is emerging, our knowledge about the control of cell expansion remains more limited. We demonstrate here that the internal-motor kinesin AtKINESIN-13A (AtKIN13A) limits cell expansion and cell size in Arabidopsis thaliana, with loss-of-function atkin13a mutants forming larger petals with larger cells. The homolog, AtKINESIN-13B, also affects cell expansion and double mutants display growth, gametophytic and early embryonic defects, indicating a redundant role of the two genes. AtKIN13A is known to depolymerize microtubules and influence Golgi motility and distribution. Consistent with this function, AtKIN13A interacts genetically with ANGUSTIFOLIA, encoding a regulator of Golgi dynamics. Reduced AtKIN13A activity alters cell wall structure as assessed by Fourier-transformed infrared-spectroscopy and triggers signalling via the THESEUS1-dependent cell-wall integrity pathway, which in turn promotes the excess cell expansion in the atkin13a mutant. Thus, our results indicate that the intracellular activity of AtKIN13A regulates cell expansion and wall architecture via THESEUS1, providing a compelling case of interplay between cell wall integrity sensing and expansion. PMID:25232944

  3. APC/C--the master controller of origin licensing?

    PubMed

    Sivaprasad, Umasundari; Machida, Yuichi J; Dutta, Anindya

    2007-02-23

    DNA replication must be tightly controlled to prevent initiation of a second round of replication until mitosis is complete. So far, components of the pre-replicative complex (Cdt1, Cdc6 and geminin) were considered key players in this regulation. In a new study, Machida and Dutta have shown that depletion of Emi1 caused cells to replicate their DNA more than once per cell cycle 1. This effect was dependent on the ability of Emi1 to inhibit the APC/C. In addition to its role in regulating entry into mitosis, oscillation of APC/C activity regulates pre-RC formation: high APC/C activity in late M/G1 allows pre-RC formation and low APC/C activity in S/G2 prevents pre-RC formation for a second time thereby preventing rereplication. Each redundant pathway to prevent rereplication is dependent on regulating one of the pre-RC components, and all of the pathways are co-regulated by Emi1 through the APC/C. In this commentary we discuss how this new role of Emi1 adds to our understanding of the regulation of replication initiation. We also review the literature to analyze whether APC/C has a role in regulating endoreduplication (a normal state of polyploidy in some differentiated cells). Similarly a role of premature APC/C activation in genomic instability of tumors is discussed.

  4. Levers and linkages: mechanical trade-offs in a power-amplified system.

    PubMed

    Anderson, Philip S L; Claverie, Thomas; Patek, S N

    2014-07-01

    Mechanical redundancy within a biomechanical system (e.g., many-to-one mapping) allows morphologically divergent organisms to maintain equivalent mechanical outputs. However, most organisms depend on the integration of more than one biomechanical system. Here, we test whether coupled mechanical systems follow a pattern of amplification (mechanical changes are congruent and evolve toward the same functional extreme) or independence (mechanisms evolve independently). We examined the correlated evolution and evolutionary pathways of the coupled four-bar linkage and lever systems in mantis shrimp (Stomatopoda) ultrafast raptorial appendages. We examined models of character evolution in the framework of two divergent groups of stomatopods-"smashers" (hammer-shaped appendages) and "spearers" (bladed appendages). Smashers tended to evolve toward force amplification, whereas spearers evolved toward displacement amplification. These findings show that coupled biomechanical systems can evolve synergistically, thereby resulting in functional amplification rather than mechanical redundancy. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  5. T-cell costimulatory pathways in allograft rejection and tolerance.

    PubMed

    Rothstein, David M; Sayegh, Mohamed H

    2003-12-01

    The destiny of activated T cells is critical to the ultimate fate of immune response. After encountering antigen, naïve T cells receive signal 1 through the T-cell receptor (TCR)-major histocompatibility complex (MHC) plus antigenic peptide complex and signal 2 through "positive" costimulatory molecules leading to full activation. "Negative" T-cell costimulatory pathways, on the other hand, function to downregulate immune responses. The purpose of this article is to review the current state of knowledge and recent advances in our understanding of the functions of the positive and negative T-cell costimulatory pathways in alloimmune responses. Specifically, we discuss the functions of the CD28:B7 and the tumor necrosis factor receptor (TNFR):tumor necrosis factor (TNF) family of molecules in allograft rejection and tolerance. We address the following important questions: are T-cell costimulatory pathways merely redundant or do they provide distinct and unique functions? What are the important and unique interactions between the various pathways? And, what are the effects and mechanisms of targeting of these pathways in different types and patterns of allograft rejection and tolerance models?

  6. RNA Pol IV and V in Gene Silencing: Rebel Polymerases Evolving Away From Pol II’s Rules

    PubMed Central

    Zhou, Ming; Law, Julie A.

    2015-01-01

    Noncoding RNAs regulate gene expression at both the transcriptional and post-transcriptional levels, and play critical roles in development, imprinting and the maintenance of genome integrity in eukaryotic organisms [1–3]. Therefore, it is important to understand how the production of such RNAs are controlled. In addition to the three canonical DNA dependent RNA polymerases (Pol) Pol I, II and III, two non-redundant plant-specific RNA polymerases, Pol IV and Pol V, have been identified and shown to generate noncoding RNAs that are required for transcriptional gene silencing via the RNA-directed DNA methylation (RdDM) pathway. Thus, somewhat paradoxically, transcription is required for gene silencing. This paradox extends beyond plants, as silencing pathways in yeast, fungi, flies, worms, and mammals also require transcriptional machinery [4,5]. As plants have evolved specialized RNA polymerases to carry out gene silencing in a manner that is separate from the essential roles of Pol II, their characterization offers unique insight into how RNA polymerases facilitate gene silencing. In this review, we focus on the mechanisms of Pol IV and Pol V function, including their compositions, their transcripts, and their modes of recruitment to chromatin. PMID:26344361

  7. A highly redundant robot system for inspection

    NASA Technical Reports Server (NTRS)

    Lee, Thomas S.; Ohms, Tim; Hayati, Samad

    1994-01-01

    The work on the serpentine inspection system at JPL is described. The configuration of the inspection system consists of 20 degrees of freedom in total. In particular, the design and development of the serpentine micromanipulator end-effector tool which has 12 degrees of freedom is described. The inspection system is used for application in JPL's Remote Surface Inspection project and as a research tool in redundant manipulator control.

  8. Doing It Right: 366 answers to computing questions you didn't know you had

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

    Herring, Stuart Davis

    Slides include information on history: version control, version control: branches, version control: Git, releases, requirements, readability, readability control flow, global variables, architecture, architecture redundancy, processes, input/output, unix, etcetera.

  9. Kinematics, controls, and path planning results for a redundant manipulator

    NASA Technical Reports Server (NTRS)

    Gretz, Bruce; Tilley, Scott W.

    1989-01-01

    The inverse kinematics solution, a modal position control algorithm, and path planning results for a 7 degree of freedom manipulator are presented. The redundant arm consists of two links with shoulder and elbow joints and a spherical wrist. The inverse kinematics problem for tip position is solved and the redundant joint is identified. It is also shown that a locus of tip positions exists in which there are kinematic limitations on self-motion. A computationally simple modal position control algorithm has been developed which guarantees a nearly constant closed-loop dynamic response throughout the workspace. If all closed-loop poles are assigned to the same location, the algorithm can be implemented with very little computation. To further reduce the required computation, the modal gains are updated only at discrete time intervals. Criteria are developed for the frequency of these updates. For commanding manipulator movements, a 5th-order spline which minimizes jerk provides a smooth tip-space path. Schemes for deriving a corresponding joint-space trajectory are discussed. Modifying the trajectory to avoid joint torque saturation when a tip payload is added is also considered. Simulation results are presented.

  10. Coping with changing controlled vocabularies.

    PubMed Central

    Cimino, J. J.; Clayton, P. D.

    1994-01-01

    For the foreseeable future, controlled medical vocabularies will be in a constant state of development, expansion and refinement. Changes in controlled vocabularies must be reconciled with historical patient information which is coded using those vocabularies and stored in clinical databases. This paper explores the kinds of changes that can occur in controlled vocabularies, including adding terms (simple additions, refinements, redundancy and disambiguation), deleting terms, changing terms (major and minor name changes), and other special situations (obsolescence, discovering redundancy, and precoordination). Examples are drawn from actual changes appearing in the 1993 update to the International Classification of Diseases (ICD9-CM). The methods being used at Columbia-Presbyterian Medical Center to reconcile its Medical Entities Dictionary and its clinical database are discussed. PMID:7949906

  11. Neutron Particle Effects on a Quad-Redundant Flight Control Computer

    NASA Technical Reports Server (NTRS)

    Eure, Kenneth; Belcastro, Celeste M.; Gray, W Steven; Gonzalex, Oscar

    2003-01-01

    This paper describes a single-event upset experiment performed at the Los Alamos National Laboratory. A closed-loop control system consisting of a Quad-Redundant Flight Control Computer (FCC) and a B737 simulator was operated while the FCC was exposed to a neutron beam. The purpose of this test was to analyze the effects of neutron bombardment on avionics control systems operating at altitudes where neutron strikes are probable. The neutron energy spectrum produced at the Los Alamos National Laboratory is similar in shape to the spectrum of atmospheric neutrons but much more intense. The higher intensity results in accelerated life tests that are representative of the actual neutron radiation that a FCC may receive over a period of years.

  12. Direct Adaptive Control of Systems with Actuator Failures: State of the Art and Continuing Challenges

    NASA Technical Reports Server (NTRS)

    Tao, Gang; Joshi, Suresh M.

    2008-01-01

    In this paper, the problem of controlling systems with failures and faults is introduced, and an overview of recent work on direct adaptive control for compensation of uncertain actuator failures is presented. Actuator failures may be characterized by some unknown system inputs being stuck at some unknown (fixed or varying) values at unknown time instants, that cannot be influenced by the control signals. The key task of adaptive compensation is to design the control signals in such a manner that the remaining actuators can automatically and seamlessly take over for the failed ones, and achieve desired stability and asymptotic tracking. A certain degree of redundancy is necessary to accomplish failure compensation. The objective of adaptive control design is to effectively use the available actuation redundancy to handle failures without the knowledge of the failure patterns, parameters, and time of occurrence. This is a challenging problem because failures introduce large uncertainties in the dynamic structure of the system, in addition to parametric uncertainties and unknown disturbances. The paper addresses some theoretical issues in adaptive actuator failure compensation: actuator failure modeling, redundant actuation requirements, plant-model matching, error system dynamics, adaptation laws, and stability, tracking, and performance analysis. Adaptive control designs can be shown to effectively handle uncertain actuator failures without explicit failure detection. Some open technical challenges and research problems in this important research area are discussed.

  13. Transcriptome analysis of the tea oil camellia (Camellia oleifera) reveals candidate drought stress genes.

    PubMed

    Dong, Bin; Wu, Bin; Hong, Wenhong; Li, Xiuping; Li, Zhuo; Xue, Li; Huang, Yongfang

    2017-01-01

    The tea-oil camellia (Camellia oleifera) is the most important oil plant in southern China, and has a strong resistance to drought and barren soil. Understanding the molecular mechanisms of drought tolerance would greatly promote its cultivation and molecular breeding. In total, we obtained 76,585 unigenes with an average length of 810 bp and an N50 of 1,092 bp. We mapped all the unigenes to the NCBI 'nr' (non-redundant), SwissProt, KEGG, and clusters of orthologous groups (COG) databases, where 52,531 (68.6%) unigenes were functionally annotated. According to the annotation, 46,171 (60.8%) unigenes belong to 338 KEGG pathways. We identified a series of unigenes that are related to the synthesis and regulation of abscisic acid (ABA), the activity of protective enzymes, vitamin B6 metabolism, the metabolism of osmolytes, and pathways related to the biosynthesis of secondary metabolites. After exposed to drought for 12 hours, the number of differentially-expressed genes (DEGs) between treated plants and control plants increased in the G4 cultivar, while there was no significant increase in the drought-tolerant C3 cultivar. DEGs associated with drought stress responsive pathways were identified by KEGG pathway enrichment analysis. Moreover, we found 789 DEGs related to transcription factors. Finally, according to the results of qRT-PCR, the expression levels of the 20 unigenes tested were consistent with the results of next-generation sequencing. In the present study, we identified a large set of cDNA unigenes from C. oleifera annotated using public databases. Further studies of DEGs involved in metabolic pathways related to drought stress and transcription will facilitate the discovery of novel genes involved in resistance to drought stress in this commercially important plant.

  14. Transcriptome analysis of the tea oil camellia (Camellia oleifera) reveals candidate drought stress genes

    PubMed Central

    Wu, Bin; Hong, Wenhong; Li, Xiuping; Li, Zhuo; Xue, Li; Huang, Yongfang

    2017-01-01

    Background The tea-oil camellia (Camellia oleifera) is the most important oil plant in southern China, and has a strong resistance to drought and barren soil. Understanding the molecular mechanisms of drought tolerance would greatly promote its cultivation and molecular breeding. Results In total, we obtained 76,585 unigenes with an average length of 810 bp and an N50 of 1,092 bp. We mapped all the unigenes to the NCBI ‘nr’ (non-redundant), SwissProt, KEGG, and clusters of orthologous groups (COG) databases, where 52,531 (68.6%) unigenes were functionally annotated. According to the annotation, 46,171 (60.8%) unigenes belong to 338 KEGG pathways. We identified a series of unigenes that are related to the synthesis and regulation of abscisic acid (ABA), the activity of protective enzymes, vitamin B6 metabolism, the metabolism of osmolytes, and pathways related to the biosynthesis of secondary metabolites. After exposed to drought for 12 hours, the number of differentially-expressed genes (DEGs) between treated plants and control plants increased in the G4 cultivar, while there was no significant increase in the drought-tolerant C3 cultivar. DEGs associated with drought stress responsive pathways were identified by KEGG pathway enrichment analysis. Moreover, we found 789 DEGs related to transcription factors. Finally, according to the results of qRT-PCR, the expression levels of the 20 unigenes tested were consistent with the results of next-generation sequencing. Conclusions In the present study, we identified a large set of cDNA unigenes from C. oleifera annotated using public databases. Further studies of DEGs involved in metabolic pathways related to drought stress and transcription will facilitate the discovery of novel genes involved in resistance to drought stress in this commercially important plant. PMID:28759610

  15. Chemical genomics: characterizing target pathways for bioactive compounds using the endomembrane trafficking network.

    PubMed

    Rodriguez-Furlán, Cecilia; Hicks, Glenn R; Norambuena, Lorena

    2014-01-01

    The plant endomembrane trafficking system is a highly complex set of processes. This complexity presents a challenge for its study. Classical plant genetics often struggles with loss-of-function lethality and gene redundancy. Chemical genomics allows overcoming many of these issues by using small molecules of natural or synthetic origin to inhibit specific trafficking proteins thereby affecting the processes in a tunable and reversible manner. Bioactive chemicals identified by high-throughput phenotype screens must be characterized in detail starting with understanding of the specific trafficking pathways affected. Here, we describe approaches to characterize bioactive compounds that perturb vesicle trafficking. This should equip researchers with practical knowledge on how to identify endomembrane-specific trafficking pathways that may be perturbed by specific compounds and will help to eventually identify molecular targets for these small molecules.

  16. A systems biology analysis of autophagy in cancer therapy.

    PubMed

    Shi, Zheng; Li, Chun-yang; Zhao, Si; Yu, Yang; An, Na; Liu, Yong-xi; Wu, Chuan-fang; Yue, Bi-song; Bao, Jin-ku

    2013-09-01

    Autophagy, which degrades redundant or damaged cellular constituents, is intricately relevant to a variety of human diseases, most notably cancer. Autophagy exerts distinct effects on cancer initiation and progression, due to the intrinsic overlapping of autophagic and cancer signalling pathways. However, due to the complexity of cancer as a systemic disease, the fate of cancer cells is not decided by any one signalling pathway. Numerous autophagic inter-connectivity and cross-talk pathways need to be further clarified at a systems level. In this review, we propose a systems biology perspective for the comprehensive analysis of the autophagy-cancer network, focusing on systems biology analysis in autophagy and cancer therapy. Together, these analyses may not only improve our understanding on autophagy-cancer relationships, but also facilitate cancer drug discovery. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. The NF-YC–RGL2 module integrates GA and ABA signalling to regulate seed germination in Arabidopsis

    PubMed Central

    Liu, Xu; Hu, Pengwei; Huang, Mingkun; Tang, Yang; Li, Yuge; Li, Ling; Hou, Xingliang

    2016-01-01

    The antagonistic crosstalk between gibberellic acid (GA) and abscisic acid (ABA) plays a pivotal role in the modulation of seed germination. However, the molecular mechanism of such phytohormone interaction remains largely elusive. Here we show that three Arabidopsis NUCLEAR FACTOR-Y C (NF-YC) homologues NF-YC3, NF-YC4 and NF-YC9 redundantly modulate GA- and ABA-mediated seed germination. These NF-YCs interact with the DELLA protein RGL2, a key repressor of GA signalling. The NF-YC–RGL2 module targets ABI5, a gene encoding a core component of ABA signalling, via specific CCAAT elements and collectively regulates a set of GA- and ABA-responsive genes, thus controlling germination. These results suggest that the NF-YC–RGL2–ABI5 module integrates GA and ABA signalling pathways during seed germination. PMID:27624486

  18. Environmental sensing by mature B cells is controlled by the transcription factors PU.1 and SpiB.

    PubMed

    Willis, Simon N; Tellier, Julie; Liao, Yang; Trezise, Stephanie; Light, Amanda; O'Donnell, Kristy; Garrett-Sinha, Lee Ann; Shi, Wei; Tarlinton, David M; Nutt, Stephen L

    2017-11-10

    Humoral immunity requires B cells to respond to multiple stimuli, including antigen, membrane and soluble ligands, and microbial products. Ets family transcription factors regulate many aspects of haematopoiesis, although their functions in humoral immunity are difficult to decipher as a result of redundancy between the family members. Here we show that mice lacking both PU.1 and SpiB in mature B cells do not generate germinal centers and high-affinity antibody after protein immunization. PU.1 and SpiB double-deficient B cells have a survival defect after engagement of CD40 or Toll-like receptors (TLR), despite paradoxically enhanced plasma cell differentiation. PU.1 and SpiB regulate the expression of many components of the B cell receptor signaling pathway and the receptors for CD40L, BAFF and TLR ligands. Thus, PU.1 and SpiB enable B cells to appropriately respond to environmental cues.

  19. Capability Description for NASA's F/A-18 TN 853 as a Testbed for the Integrated Resilient Aircraft Control Project

    NASA Technical Reports Server (NTRS)

    Hanson, Curt

    2009-01-01

    The NASA F/A-18 tail number (TN) 853 full-scale Integrated Resilient Aircraft Control (IRAC) testbed has been designed with a full array of capabilities in support of the Aviation Safety Program. Highlights of the system's capabilities include: 1) a quad-redundant research flight control system for safely interfacing controls experiments to the aircraft's control surfaces; 2) a dual-redundant airborne research test system for hosting multi-disciplinary state-of-the-art adaptive control experiments; 3) a robust reversionary configuration for recovery from unusual attitudes and configurations; 4) significant research instrumentation, particularly in the area of static loads; 5) extensive facilities for experiment simulation, data logging, real-time monitoring and post-flight analysis capabilities; and 6) significant growth capability in terms of interfaces and processing power.

  20. [Advanced Development for Space Robotics With Emphasis on Fault Tolerance Technology

    NASA Technical Reports Server (NTRS)

    Tesar, Delbert

    1997-01-01

    This report describes work developing fault tolerant redundant robotic architectures and adaptive control strategies for robotic manipulator systems which can dynamically accommodate drastic robot manipulator mechanism, sensor or control failures and maintain stable end-point trajectory control with minimum disturbance. Kinematic designs of redundant, modular, reconfigurable arms for fault tolerance were pursued at a fundamental level. The approach developed robotic testbeds to evaluate disturbance responses of fault tolerant concepts in robotic mechanisms and controllers. The development was implemented in various fault tolerant mechanism testbeds including duality in the joint servo motor modules, parallel and serial structural architectures, and dual arms. All have real-time adaptive controller technologies to react to mechanism or controller disturbances (failures) to perform real-time reconfiguration to continue the task operations. The developments fall into three main areas: hardware, software, and theoretical.

  1. Redundant control of migration and adhesion by ERM proteins in vascular smooth muscle cells

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

    Baeyens, Nicolas; Latrache, Iman; Yerna, Xavier

    Highlights: •The three ERM proteins are expressed in vascular smooth muscle cell. •ERM depletion inhibited PDGF-evoked migration redundantly. •ERM depletion increased cell adhesion redundantly. •ERM depletion did not affect PDGF-evoked Ca signal, Rac1 activation, proliferation. •ERM proteins control PDGF-induced migration by regulating adhesion. -- Abstract: Ezrin, radixin, and moesin possess a very similar structure with a C-terminal actin-binding domain and a N-terminal FERM interacting domain. They are known to be involved in cytoskeleton organization in several cell types but their function in vascular smooth muscle cells (VSMC) is still unknown. The aim of this study was to investigate the rolemore » of ERM proteins in cell migration induced by PDGF, a growth factor involved in pathophysiological processes like angiogenesis or atherosclerosis. We used primary cultured VSMC obtained from rat aorta, which express the three ERM proteins. Simultaneous depletion of the three ERM proteins with specific siRNAs abolished the effects of PDGF on cell architecture and migration and markedly increased cell adhesion and focal adhesion size, while these parameters were only slightly affected by depletion of ezrin, radixin or moesin alone. Rac1 activation, cell proliferation, and Ca{sup 2+} signal in response to PDGF were unaffected by ERM depletion. These results indicate that ERM proteins exert a redundant control on PDGF-induced VSMC migration by regulating focal adhesion turn-over and cell adhesion to substrate.« less

  2. Metabolic network visualization eliminating node redundance and preserving metabolic pathways

    PubMed Central

    Bourqui, Romain; Cottret, Ludovic; Lacroix, Vincent; Auber, David; Mary, Patrick; Sagot, Marie-France; Jourdan, Fabien

    2007-01-01

    Background The tools that are available to draw and to manipulate the representations of metabolism are usually restricted to metabolic pathways. This limitation becomes problematic when studying processes that span several pathways. The various attempts that have been made to draw genome-scale metabolic networks are confronted with two shortcomings: 1- they do not use contextual information which leads to dense, hard to interpret drawings, 2- they impose to fit to very constrained standards, which implies, in particular, duplicating nodes making topological analysis considerably more difficult. Results We propose a method, called MetaViz, which enables to draw a genome-scale metabolic network and that also takes into account its structuration into pathways. This method consists in two steps: a clustering step which addresses the pathway overlapping problem and a drawing step which consists in drawing the clustered graph and each cluster. Conclusion The method we propose is original and addresses new drawing issues arising from the no-duplication constraint. We do not propose a single drawing but rather several alternative ways of presenting metabolism depending on the pathway on which one wishes to focus. We believe that this provides a valuable tool to explore the pathway structure of metabolism. PMID:17608928

  3. Lens fibre cell differentiation and organelle loss: many paths lead to clarity

    PubMed Central

    Wride, Michael A.

    2011-01-01

    The programmed removal of organelles from differentiating lens fibre cells contributes towards lens transparency through formation of an organelle-free zone (OFZ). Disruptions in OFZ formation are accompanied by the persistence of organelles in lens fibre cells and can contribute towards cataract. A great deal of work has gone into elucidating the nature of the mechanisms and signalling pathways involved. It is apparent that multiple, parallel and redundant pathways are involved in this process and that these pathways form interacting networks. Furthermore, it is possible that the pathways can functionally compensate for each other, for example in mouse knockout studies. This makes sense given the importance of lens clarity in an evolutionary context. Apoptosis signalling and proteolytic pathways have been implicated in both lens fibre cell differentiation and organelle loss, including the Bcl-2 and inhibitor of apoptosis families, tumour necrosis factors, p53 and its regulators (such as Mdm2) and proteolytic enzymes, including caspases, cathepsins, calpains and the ubiquitin–proteasome pathway. Ongoing approaches being used to dissect the molecular pathways involved, such as transgenics, lens-specific gene deletion and zebrafish mutants, are discussed here. Finally, some of the remaining unresolved issues and potential areas for future studies are highlighted. PMID:21402582

  4. Lung cancer risk associated with Thr495Pro polymorphism of GHR in Chinese population.

    PubMed

    Cao, Guochun; Lu, Hongna; Feng, Jifeng; Shu, Jian; Zheng, Datong; Hou, Yayi

    2008-04-01

    The incidence of lung cancer has been increasing over recent decades. Previous studies showed that polymorphisms of the genes involved in carcinogen-detoxication, DNA repair and cell cycle control comprise risk factors for lung cancer. Recent observations revealed that the growth hormone receptor (GHR) might play important roles in carcinogenesis and Rudd et al. found that the Thr495Pro polymorphism of GHR was strongly associated with lung cancer risk in Caucasians living in the UK (OR = 12.98, P = 0.0019, 95% CI: 1.77-infinity). To test whether this variant of GHR would modify the risk of lung cancer in Chinese population, we compared the polymorphism between 778 lung cancer patients and 781 healthy control subjects. Our results indicate that the frequency of 495Thr (2.8%) allele in cases was significantly higher than in controls (OR = 2.04, P = 0.006, 95% CI: 1.21-3.42) which indicated this allele might be a risk factor for lung cancer. Further analyses revealed Thr495Pro variant was associated with lung cancer in the subpopulation with higher risk for lung cancer: male subpopulation, still-smokers subpopulation and the subpopulation with familial history of cancer. In different histological types of lung cancer, Thr495Pro SNP was significantly associated with small cell and squamous cell lung cancer, but not with adenocarcinoma, which suggested a potential interaction between this polymorphism and metabolic pathways related to smoking. The potential gene-environment interaction on lung cancer risk was evaluated using MDR software. A significant redundant interaction between Thr495Pro polymorphism and smoking dose and familial history of cancer was identified and the combination of genetic factors and smoking status or familial history of cancer barely increased the cancer risk prediction accuracy. In conclusion, our results suggested that the Thr495Pro polymorphism of GHR was associated with the risk of lung cancer in a redundant interaction with smoking and familial history of cancer.

  5. Most Colorful Example of Genetic Assimilation? Exploring the Evolutionary Destiny of Recurrent Phenotypic Accommodation.

    PubMed

    Badyaev, Alexander V; Potticary, Ahva L; Morrison, Erin S

    2017-08-01

    Evolution of adaptation requires both generation of novel phenotypic variation and retention of a locally beneficial subset of this variation. Such retention can be facilitated by genetic assimilation, the accumulation of genetic and molecular mechanisms that stabilize induced phenotypes and assume progressively greater control over their reliable production. A particularly strong inference into genetic assimilation as an evolutionary process requires a system where it is possible to directly evaluate the extent to which an induced phenotype is progressively incorporated into preexisting developmental pathways. Evolution of diet-dependent pigmentation in birds-where external carotenoids are coopted into internal metabolism to a variable degree before being integrated with a feather's developmental processes-provides such an opportunity. Here we combine a metabolic network view of carotenoid evolution with detailed empirical study of feather modifications to show that the effect of physical properties of carotenoids on feather structure depends on their metabolic modification, their environmental recurrence, and biochemical redundancy, as predicted by the genetic assimilation hypothesis. Metabolized carotenoids caused less stochastic variation in feather structure and were more closely integrated with feather growth than were dietary carotenoids of the same molecular weight. These patterns were driven by the recurrence of organism-carotenoid associations: commonly used dietary carotenoids and biochemically redundant derived carotenoids caused less stochastic variation in feather structure than did rarely used or biochemically unique compounds. We discuss implications of genetic assimilation processes for the evolutionary diversification of diet-dependent animal coloration.

  6. Genome-wide DNA methylation patterns in LSH mutant reveals de-repression of repeat elements and redundant epigenetic silencing pathways

    PubMed Central

    Yu, Weishi; McIntosh, Carl; Lister, Ryan; Zhu, Iris; Han, Yixing; Ren, Jianke; Landsman, David; Lee, Eunice; Briones, Victorino; Terashima, Minoru; Leighty, Robert; Ecker, Joseph R.

    2014-01-01

    Cytosine methylation is critical in mammalian development and plays a role in diverse biologic processes such as genomic imprinting, X chromosome inactivation, and silencing of repeat elements. Several factors regulate DNA methylation in early embryogenesis, but their precise role in the establishment of DNA methylation at a given site remains unclear. We have generated a comprehensive methylation map in fibroblasts derived from the murine DNA methylation mutant Hells−/− (helicase, lymphoid specific, also known as LSH). It has been previously shown that HELLS can influence de novo methylation of retroviral sequences and endogenous genes. Here, we describe that HELLS controls cytosine methylation in a nuclear compartment that is in part defined by lamin B1 attachment regions. Despite widespread loss of cytosine methylation at regulatory sequences, including promoter regions of protein-coding genes and noncoding RNA genes, overall relative transcript abundance levels in the absence of HELLS are similar to those in wild-type cells. A subset of promoter regions shows increases of the histone modification H3K27me3, suggesting redundancy of epigenetic silencing mechanisms. Furthermore, HELLS modulates CG methylation at all classes of repeat elements and is critical for repression of a subset of repeat elements. Overall, we provide a detailed analysis of gene expression changes in relation to DNA methylation alterations, which contributes to our understanding of the biological role of cytosine methylation. PMID:25170028

  7. Redundant electronic circuit provides fail-safe control

    NASA Technical Reports Server (NTRS)

    Archer, J. W.

    1970-01-01

    Circuit using dual control amplifiers and dual position demand potentiometers powered from separate sources is used for reliable hydraulic valve controller that prevents closure of valve when control circuits fail, and maintains valve control to close tolerance for more common modes of controller failure.

  8. Characterization of Spleen Transcriptome of Schizothorax prenanti during Aeromonas hydrophila Infection.

    PubMed

    Ye, Hua; Xiao, Shijun; Wang, Xiaoqing; Wang, Zhiyong; Zhang, Zhengshi; Zhu, Chengke; Hu, Bingjie; Lv, Changhuan; Zheng, Shuming; Luo, Hui

    2018-04-01

    Schizothorax prenanti (S. prenanti) is an indigenous fish species and is popularly cultured in southwestern China. In recent years, intensive farming of S. prenanti and water quality deterioration has increased the susceptibility of this fish to various pathogens, including Aeromonas hydrophila (A. hydrophila), which has caused severe damage to S. prenanti production. However, the understanding of molecular immune response of S. prenanti to A. hydrophila infection is still lacking. In order to better comprehend the S. prenanti time series immune response process against A. hydrophila, we conducted the first transcriptomic comparison in S. prenanti spleen at 4, 24, and 48 h after the infection challenge of A. hydrophila against their control counterparts. In total, 628 million clean reads were obtained from 18 libraries and assembled into 262,745 transcripts. After eliminating sequence redundancy, 69,373 unigenes with an average length of 1476 bp were obtained. Comparative analysis revealed 1890 unigenes with significantly differential expression, including 172, 455, 589 upregulated and 27, 676, 551 unigenes downregulated genes for 4, 24, and 48 h post-infection, respectively. Differentially expressed genes (DEGs) were validated using qPCR for 15 randomly selected genes. Enrichment and pathway analysis of DEGs was carried out to understand the functions of the immune-related genes. Our results revealed that many important functional genes relating to complement and coagulation cascades, chemokine signaling pathway, toll-like receptor signaling pathway, NOD-like receptor signaling pathway and leukocyte transendothelial migration were regulated during the infection of A. hydrophila, and the expression of those genes reflected the transcriptome profiles during the challenging stages.

  9. Unlocking Sensitivity for Visibility-based Estimators of the 21 cm Reionization Power Spectrum

    NASA Astrophysics Data System (ADS)

    Zhang, Yunfan Gerry; Liu, Adrian; Parsons, Aaron R.

    2018-01-01

    Radio interferometers designed to measure the cosmological 21 cm power spectrum require high sensitivity. Several modern low-frequency interferometers feature drift-scan antennas placed on a regular grid to maximize the number of instantaneously coherent (redundant) measurements. However, even for such maximum-redundancy arrays, significant sensitivity comes through partial coherence between baselines. Current visibility-based power-spectrum pipelines, though shown to ease control of systematics, lack the ability to make use of this partial redundancy. We introduce a method to leverage partial redundancy in such power-spectrum pipelines for drift-scan arrays. Our method cross-multiplies baseline pairs at a time lag and quantifies the sensitivity contributions of each pair of baselines. Using the configurations and beams of the 128-element Donald C. Backer Precision Array for Probing the Epoch of Reionization (PAPER-128) and staged deployments of the Hydrogen Epoch of Reionization Array, we illustrate how our method applies to different arrays and predict the sensitivity improvements associated with pairing partially coherent baselines. As the number of antennas increases, we find partial redundancy to be of increasing importance in unlocking the full sensitivity of upcoming arrays.

  10. Complex two-component signaling regulates the general stress response in Alphaproteobacteria.

    PubMed

    Kaczmarczyk, Andreas; Hochstrasser, Ramon; Vorholt, Julia A; Francez-Charlot, Anne

    2014-12-02

    The general stress response (GSR) in Alphaproteobacteria was recently shown to be controlled by a partner-switching mechanism that is triggered by phosphorylation of the response regulator PhyR. Activation of PhyR ultimately results in release of the alternative extracytoplasmic function sigma factor σ(EcfG), which redirects transcription toward the GSR. Little is known about the signal transduction pathway(s) controlling PhyR phosphorylation. Here, we identified the single-domain response regulator (SDRR) SdrG and seven histidine kinases, PakA to PakG, belonging to the HWE/HisKA2 family as positive modulators of the GSR in Sphingomonas melonis Fr1. Phenotypic analyses, epistasis experiments, and in vitro phosphorylation assays indicate that Paks directly phosphorylate PhyR and SdrG, and that SdrG acts upstream of or in concert with PhyR, modulating its activity in a nonlinear pathway. Furthermore, we found that additional SDRRs negatively affect the GSR in a way that strictly requires PhyR and SdrG. Finally, analysis of GSR activation by thermal, osmotic, and oxidative stress indicates that Paks display different degrees of redundancy and that a specific kinase can sense multiple stresses, suggesting that the GSR senses a particular condition as a combination of, rather than individual, molecular cues. This study thus establishes the alphaproteobacterial GSR as a complex and interlinked network of two-component systems, in which multiple histidine kinases converge to PhyR, the phosphorylation of which is, in addition, subject to regulation by several SDRRs. Our finding that most HWE/HisKA2 kinases contribute to the GSR in S. melonis Fr1 opens the possibility that this notion might also be true for other Alphaproteobacteria.

  11. Insights into Land Plant Evolution Garnered from the Marchantia polymorpha Genome.

    PubMed

    Bowman, John L; Kohchi, Takayuki; Yamato, Katsuyuki T; Jenkins, Jerry; Shu, Shengqiang; Ishizaki, Kimitsune; Yamaoka, Shohei; Nishihama, Ryuichi; Nakamura, Yasukazu; Berger, Frédéric; Adam, Catherine; Aki, Shiori Sugamata; Althoff, Felix; Araki, Takashi; Arteaga-Vazquez, Mario A; Balasubrmanian, Sureshkumar; Barry, Kerrie; Bauer, Diane; Boehm, Christian R; Briginshaw, Liam; Caballero-Perez, Juan; Catarino, Bruno; Chen, Feng; Chiyoda, Shota; Chovatia, Mansi; Davies, Kevin M; Delmans, Mihails; Demura, Taku; Dierschke, Tom; Dolan, Liam; Dorantes-Acosta, Ana E; Eklund, D Magnus; Florent, Stevie N; Flores-Sandoval, Eduardo; Fujiyama, Asao; Fukuzawa, Hideya; Galik, Bence; Grimanelli, Daniel; Grimwood, Jane; Grossniklaus, Ueli; Hamada, Takahiro; Haseloff, Jim; Hetherington, Alexander J; Higo, Asuka; Hirakawa, Yuki; Hundley, Hope N; Ikeda, Yoko; Inoue, Keisuke; Inoue, Shin-Ichiro; Ishida, Sakiko; Jia, Qidong; Kakita, Mitsuru; Kanazawa, Takehiko; Kawai, Yosuke; Kawashima, Tomokazu; Kennedy, Megan; Kinose, Keita; Kinoshita, Toshinori; Kohara, Yuji; Koide, Eri; Komatsu, Kenji; Kopischke, Sarah; Kubo, Minoru; Kyozuka, Junko; Lagercrantz, Ulf; Lin, Shih-Shun; Lindquist, Erika; Lipzen, Anna M; Lu, Chia-Wei; De Luna, Efraín; Martienssen, Robert A; Minamino, Naoki; Mizutani, Masaharu; Mizutani, Miya; Mochizuki, Nobuyoshi; Monte, Isabel; Mosher, Rebecca; Nagasaki, Hideki; Nakagami, Hirofumi; Naramoto, Satoshi; Nishitani, Kazuhiko; Ohtani, Misato; Okamoto, Takashi; Okumura, Masaki; Phillips, Jeremy; Pollak, Bernardo; Reinders, Anke; Rövekamp, Moritz; Sano, Ryosuke; Sawa, Shinichiro; Schmid, Marc W; Shirakawa, Makoto; Solano, Roberto; Spunde, Alexander; Suetsugu, Noriyuki; Sugano, Sumio; Sugiyama, Akifumi; Sun, Rui; Suzuki, Yutaka; Takenaka, Mizuki; Takezawa, Daisuke; Tomogane, Hirokazu; Tsuzuki, Masayuki; Ueda, Takashi; Umeda, Masaaki; Ward, John M; Watanabe, Yuichiro; Yazaki, Kazufumi; Yokoyama, Ryusuke; Yoshitake, Yoshihiro; Yotsui, Izumi; Zachgo, Sabine; Schmutz, Jeremy

    2017-10-05

    The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), expanded repertoires of signaling pathways, and increased diversity in some transcription factor families. Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant. PAPERCLIP. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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

    NASA Technical Reports Server (NTRS)

    Mukhopadhyay, A. K.

    1975-01-01

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

  13. Perspective on the combined use of an independent transgenic sexing and a multifactorial reproductive sterility system to avoid resistance development against transgenic Sterile Insect Technique approaches

    PubMed Central

    2014-01-01

    Background The Sterile Insect Technique (SIT) is an accepted species-specific genetic control approach that acts as an insect birth control measure, which can be improved by biotechnological engineering to facilitate its use and widen its applicability. First transgenic insects carrying a single killing system have already been released in small scale trials. However, to evade resistance development to such transgenic approaches, completely independent ways of transgenic killing should be established and combined. Perspective Most established transgenic sexing and reproductive sterility systems are based on the binary tTA expression system that can be suppressed by adding tetracycline to the food. However, to create 'redundant killing' an additional independent conditional expression system is required. Here we present a perspective on the use of a second food-controllable binary expression system - the inducible Q system - that could be used in combination with site-specific recombinases to generate independent transgenic killing systems. We propose the combination of an already established transgenic embryonic sexing system to meet the SIT requirement of male-only releases based on the repressible tTA system together with a redundant male-specific reproductive sterility system, which is activated by Q-system controlled site-specific recombination and is based on a spermatogenesis-specifically expressed endonuclease acting on several species-specific target sites leading to chromosome shredding. Conclusion A combination of a completely independent transgenic sexing and a redundant reproductive male sterility system, which do not share any active components and mediate the induced lethality by completely independent processes, would meet the 'redundant killing' criteria for suppression of resistance development and could therefore be employed in large scale long-term suppression programs using biotechnologically enhanced SIT. PMID:25471733

  14. CONSERVED ROLES FOR CYTOSKELETAL COMPONENTS IN DETERMINING LATERALITY

    PubMed Central

    McDowell, Gary S.; Lemire, Joan M.; Paré, Jean-Francois; Cammarata, Garrett; Lowery, Laura Anne; Levin, Michael

    2016-01-01

    SUMMARY Consistently-biased left-right (LR) patterning is required for the proper placement of organs including the heart and viscera. The LR axis is especially fascinating as an example of multi-scale pattern formation, since here chiral events at the subcellular level are integrated and amplified into asymmetric transcriptional cascades and ultimately into the anatomical patterning of the entire body. In contrast to the other two body axes, there is considerable controversy about the earliest mechanisms of embryonic laterality. Many molecular components of asymmetry have not been widely tested among phyla with diverse bodyplans, and it is unknown whether parallel (redundant) pathways may exist that could reverse abnormal asymmetry states at specific checkpoints in development. To address conservation of the early steps of LR patterning, we used the Xenopus laevis (frog) embryo to functionally test a number of protein targets known to direct asymmetry in plants, fruit fly, and rodent. Using the same reagents that randomize asymmetry in Arabidopsis, Drosophila, and mouse embryos, we show that manipulation of the microtubule and actin cytoskeleton immediately post-fertilization, but not later, results in laterality defects in Xenopus embryos. Moreover, we observed organ-specific randomization effects and a striking dissociation of organ situs from effects on the expression of left side control genes, which parallel data from Drosophila and mouse. Remarkably, some early manipulations that disrupt laterality of transcriptional asymmetry determinants can be subsequently “rescued” by the embryo, resulting in normal organ situs. These data reveal the existence of novel corrective mechanisms, demonstrate that asymmetric expression of Nodal is not a definitive marker of laterality, and suggest the existence of amplification pathways that connect early cytoskeletal processes to control of organ situs bypassing Nodal. Counter to alternative models of symmetry breaking during neurulation (via ciliary structures absent in many phyla), our data suggest a widely-conserved role for the cytoskeleton in regulating left-right axis formation immediately after fertilization of the egg. The novel mechanisms that rescue organ situs, even after incorrect expression of genes previously considered to be left-side master regulators, suggest LR patterning as a new context in which to explore multi-scale redundancy and integration of patterning from the subcellular structure to the entire bodyplan. PMID:26928161

  15. Characterization of the periplasmic redox network that sustains the versatile anaerobic metabolism of Shewanella oneidensis MR-1

    PubMed Central

    Alves, Mónica N.; Neto, Sónia E.; Alves, Alexandra S.; Fonseca, Bruno M.; Carrêlo, Afonso; Pacheco, Isabel; Paquete, Catarina M.; Soares, Cláudio M.; Louro, Ricardo O.

    2015-01-01

    The versatile anaerobic metabolism of the Gram-negative bacterium Shewanella oneidensis MR-1 (SOMR-1) relies on a multitude of redox proteins found in its periplasm. Most are multiheme cytochromes that carry electrons to terminal reductases of insoluble electron acceptors located at the cell surface, or bona fide terminal reductases of soluble electron acceptors. In this study, the interaction network of several multiheme cytochromes was explored by a combination of NMR spectroscopy, activity assays followed by UV-visible spectroscopy and comparison of surface electrostatic potentials. From these data the small tetraheme cytochrome (STC) emerges as the main periplasmic redox shuttle in SOMR-1. It accepts electrons from CymA and distributes them to a number of terminal oxidoreductases involved in the respiration of various compounds. STC is also involved in the electron transfer pathway to reduce nitrite by interaction with the octaheme tetrathionate reductase (OTR), but not with cytochrome c nitrite reductase (ccNiR). In the main pathway leading the metal respiration STC pairs with flavocytochrome c (FccA), the other major periplasmic cytochrome, which provides redundancy in this important pathway. The data reveals that the two proteins compete for the binding site at the surface of MtrA, the decaheme cytochrome inserted on the periplasmic side of the MtrCAB–OmcA outer-membrane complex. However, this is not observed for the MtrA homologues. Indeed, neither STC nor FccA interact with MtrD, the best replacement for MtrA, and only STC is able to interact with the decaheme cytochrome DmsE of the outer-membrane complex DmsEFABGH. Overall, these results shown that STC plays a central role in the anaerobic respiratory metabolism of SOMR-1. Nonetheless, the trans-periplasmic electron transfer chain is functionally resilient as a consequence of redundancies that arise from the presence of alternative pathways that bypass/compete with STC. PMID:26175726

  16. Message passing for integrating and assessing renewable generation in a redundant power grid

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

    Zdeborova, Lenka; Backhaus, Scott; Chertkov, Michael

    2009-01-01

    A simplified model of a redundant power grid is used to study integration of fluctuating renewable generation. The grid consists of large number of generator and consumer nodes. The net power consumption is determined by the difference between the gross consumption and the level of renewable generation. The gross consumption is drawn from a narrow distribution representing the predictability of aggregated loads, and we consider two different distributions representing wind and solar resources. Each generator is connected to D consumers, and redundancy is built in by connecting R {le} D of these consumers to other generators. The lines are switchablemore » so that at any instance each consumer is connected to a single generator. We explore the capacity of the renewable generation by determining the level of 'firm' generation capacity that can be displaced for different levels of redundancy R. We also develop message-passing control algorithm for finding switch sellings where no generator is overloaded.« less

  17. Man-machine interface and control of the shuttle digital flight system

    NASA Technical Reports Server (NTRS)

    Burghduff, R. D.; Lewis, J. L., Jr.

    1985-01-01

    The space shuttle main engine (SSME) presented new requirements in the design of controls for large pump fed liquid rocket engine systems. These requirements were the need for built in full mission support capability, and complexity and flexibility of function not previously needed in this type of application. An engine mounted programmable digital control system was developed to meet these requirements. The engine system and controller and their function are described. Design challenges encountered during the course of development included accommodation for a very severe engine environment, the implementation of redundancy and redundancy management to provide fail operational/fail safe capability, removal of heat from the package, and significant constraints on computer memory size and processing time. The flexibility offered by programmable control reshaped the approach to engine design and development and set the pattern for future controls development in these types of applications.

  18. Neurotrophins, growth-factor-regulated genes and the control of energy balance.

    PubMed

    Salton, Stephen R J

    2003-03-01

    Neurotrophic growth factors are proteins that control neuronal differentiation and survival, and consequently play important roles in the developing and adult stages of the nervous system. Study of the genes that are regulated by these growth factors has provided insight into the proteins that are critical to the maturation of the nervous system, suggesting that select neurotrophins may play a role in the control of body homeostasis by the brain and peripheral nervous system. Our understanding of the mechanisms of action of neurotrophic growth factors has increased through experimental manipulation of cultured neurons and neuronal cell lines. In particular, the PC12 pheochromocytoma cell line, which displays many properties of adrenal chromaffin cells and undergoes differentiation into sympathetic neuron-like cells when treated with nerve growth factor, has been extensively investigated to identify components of neurotrophin signaling pathways as well as the genes that they regulate. VGF was one of the first neurotrophin-regulated clones identified in NGF-treated PC12 cells. Subsequent studies indicate that the vgf gene is regulated in vivo in the nervous system by neurotrophins, by electrical activity, in response to injury or seizure, and by feeding and the circadian clock. The vgf gene encodes a polypeptide rich in paired basic amino acids; this polypeptide is differentially processed in neuronal and neuroendocrine cells and is released via the regulated secretory pathway. Generation and analysis of knockout mice that fail to synthesize VGF indicate that this protein plays a critical, non-redundant role in the regulation of energy homeostasis, providing a possible link between neurotrophin function in the nervous system and the peripheral control of feeding and metabolic activity. Future experiments should clarify the sites and mechanisms of action of this neurotrophin-regulated neuronal and neuroendocrine protein.

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

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

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

    2009-01-30

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

  20. Airborne Advanced Reconfigurable Computer System (ARCS)

    NASA Technical Reports Server (NTRS)

    Bjurman, B. E.; Jenkins, G. M.; Masreliez, C. J.; Mcclellan, K. L.; Templeman, J. E.

    1976-01-01

    A digital computer subsystem fault-tolerant concept was defined, and the potential benefits and costs of such a subsystem were assessed when used as the central element of a new transport's flight control system. The derived advanced reconfigurable computer system (ARCS) is a triple-redundant computer subsystem that automatically reconfigures, under multiple fault conditions, from triplex to duplex to simplex operation, with redundancy recovery if the fault condition is transient. The study included criteria development covering factors at the aircraft's operation level that would influence the design of a fault-tolerant system for commercial airline use. A new reliability analysis tool was developed for evaluating redundant, fault-tolerant system availability and survivability; and a stringent digital system software design methodology was used to achieve design/implementation visibility.

  1. Growth condition dependency is the major cause of non-responsiveness upon genetic perturbation

    PubMed Central

    Amini, Saman; Holstege, Frank C. P.

    2017-01-01

    Investigating the role and interplay between individual proteins in biological processes is often performed by assessing the functional consequences of gene inactivation or removal. Depending on the sensitivity of the assay used for determining phenotype, between 66% (growth) and 53% (gene expression) of Saccharomyces cerevisiae gene deletion strains show no defect when analyzed under a single condition. Although it is well known that this non-responsive behavior is caused by different types of redundancy mechanisms or by growth condition/cell type dependency, it is not known what the relative contribution of these different causes is. Understanding the underlying causes of and their relative contribution to non-responsive behavior upon genetic perturbation is extremely important for designing efficient strategies aimed at elucidating gene function and unraveling complex cellular systems. Here, we provide a systematic classification of the underlying causes of and their relative contribution to non-responsive behavior upon gene deletion. The overall contribution of redundancy to non-responsive behavior is estimated at 29%, of which approximately 17% is due to homology-based redundancy and 12% is due to pathway-based redundancy. The major determinant of non-responsiveness is condition dependency (71%). For approximately 14% of protein complexes, just-in-time assembly can be put forward as a potential mechanistic explanation for how proteins can be regulated in a condition dependent manner. Taken together, the results underscore the large contribution of growth condition requirement to non-responsive behavior, which needs to be taken into account for strategies aimed at determining gene function. The classification provided here, can also be further harnessed in systematic analyses of complex cellular systems. PMID:28257504

  2. Oncogenic c-Myc-induced lymphomagenesis is inhibited non-redundantly by the p19Arf–Mdm2–p53 and RP–Mdm2–p53 pathways

    PubMed Central

    Meng, X; Carlson, NR; Dong, J; Zhang, Y

    2016-01-01

    The multifaceted oncogene c-Myc plays important roles in the development and progression of human cancer. Recent in vitro and in vivo studies have shown that the p19Arf–Mdm2–p53 and the ribosomal protein (RP)–Mdm2–p53 pathways are both essential in preventing oncogenic c-Myc-induced tumorigenesis. Disruption of each pathway individually by p19Arf deletion or by Mdm2C305F mutation, which disrupts RP-Mdm2 binding, accelerates Eμ-myc transgene-induced pre-B/B-cell lymphoma in mice at seemingly similar paces with median survival around 10 and 11 weeks, respectively, compared to 20 weeks for Eμ-myc transgenic mice. Because p19Arf can inhibit ribosomal biogenesis through its interaction with nucleophosmin (NPM/B23), RNA helicase DDX5 and RNA polymerase I transcription termination factor (TTF-I), it has been speculated that the p19Arf–Mdm2–p53 and the RP–Mdm2–p53 pathways might be a single p19Arf–RP–Mdm2–p53 pathway, in which p19Arf activates p53 by inhibiting RP biosynthesis; thus, p19Arf deletion or Mdm2C305F mutation would result in similar consequences. Here, we generated mice with concurrent p19Arf deletion and Mdm2C305F mutation and investigated the compound mice for tumorigenesis in the absence and the presence of oncogenic c-Myc overexpression. In the absence of Eμ-myc transgene, the Mdm2C305F mutation did not elicit spontaneous tumors in mice, nor did it accelerate spontaneous tumors in mice with p19Arf deletion. In the presence of Eμ-myc transgene, however, Mdm2C305F mutation significantly accelerated p19Arf deletion-induced lymphomagenesis and promoted rapid metastasis. We found that when p19Arf–Mdm2–p53 and RP–Mdm2–p53 pathways are independently disrupted, oncogenic c-Myc-induced p53 stabilization and activation is only partially attenuated. When both pathways are concurrently disrupted, however, c-Myc-induced p53 stabilization and activation are essentially obliterated. Thus, the p19Arf–Mdm2–p53 and the RP–Mdm2–p53 are non-redundant pathways possessing similar capabilities to activate p53 upon c-Myc overexpression. PMID:25823025

  3. Viking Orbiter 1975 articulation control subsystem design analysis

    NASA Technical Reports Server (NTRS)

    Horiuchi, H. H.; Vallas, L. J.

    1973-01-01

    The articulation control subsystem, developed for the Viking Orbiter 1975 spacecraft, is a digital, multiplexed, closed-loop servo system used to control the pointing and positioning of the science scan platform and the high-gain communication antenna, and to position the solar-energy controller louver blades for the thermal control of the propellant tanks. The development, design, and anlaysis of the subsystem is preliminary. The subsystem consists of a block-redundant control electronics multiplexed among eight control actuators. Each electronics block is capable of operating either individually or simultaneously with the second block. This provides the subsystem the capability of simultaneous two-actuator control or a single actuator control with the second block in a stand-by redundant mode. The result of the preliminary design and analysis indicates that the subsystem will perform satisfactorily in the Viking Orbiter 1975 mission. Some of the parameter values used, particularly those in the subsystem dynamics and the error estimates, are preliminary and the results will be updated as more accurate parameter values become available.

  4. Fragment-based drug discovery of potent and selective MKK3/6 inhibitors.

    PubMed

    Adams, Mark; Kobayashi, Toshitake; Lawson, J David; Saitoh, Morihisa; Shimokawa, Kenichiro; Bigi, Simone V; Hixon, Mark S; Smith, Christopher R; Tatamiya, Takayuki; Goto, Masayuki; Russo, Joseph; Grimshaw, Charles E; Swann, Steven

    2016-02-01

    The MAPK signaling cascade, comprised of several linear and intersecting pathways, propagates signaling into the nucleus resulting in cytokine and chemokine release. The Map Kinase Kinase isoforms 3 and 6 (MKK3 and MKK6) are responsible for the phosphorylation and activation of p38, and are hypothesized to play a key role in regulating this pathway without the redundancy seen in downstream effectors. Using FBDD, we have discovered efficient and selective inhibitors of MKK3 and MKK6 that can serve as tool molecules to help further understand the role of these kinases in MAPK signaling, and the potential impact of inhibiting kinases upstream of p38. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Metabolic Respiration Induces AMPK- and Ire1p-Dependent Activation of the p38-Type HOG MAPK Pathway

    PubMed Central

    Adhikari, Hema; Cullen, Paul J.

    2014-01-01

    Evolutionarily conserved mitogen activated protein kinase (MAPK) pathways regulate the response to stress as well as cell differentiation. In Saccharomyces cerevisiae, growth in non-preferred carbon sources (like galactose) induces differentiation to the filamentous cell type through an extracellular-signal regulated kinase (ERK)-type MAPK pathway. The filamentous growth MAPK pathway shares components with a p38-type High Osmolarity Glycerol response (HOG) pathway, which regulates the response to changes in osmolarity. To determine the extent of functional overlap between the MAPK pathways, comparative RNA sequencing was performed, which uncovered an unexpected role for the HOG pathway in regulating the response to growth in galactose. The HOG pathway was induced during growth in galactose, which required the nutrient regulatory AMP-dependent protein kinase (AMPK) Snf1p, an intact respiratory chain, and a functional tricarboxylic acid (TCA) cycle. The unfolded protein response (UPR) kinase Ire1p was also required for HOG pathway activation in this context. Thus, the filamentous growth and HOG pathways are both active during growth in galactose. The two pathways redundantly promoted growth in galactose, but paradoxically, they also inhibited each other's activities. Such cross-modulation was critical to optimize the differentiation response. The human fungal pathogen Candida albicans showed a similar regulatory circuit. Thus, an evolutionarily conserved regulatory axis links metabolic respiration and AMPK to Ire1p, which regulates a differentiation response involving the modulated activity of ERK and p38 MAPK pathways. PMID:25356552

  6. Advanced control schemes and kinematic analysis for a kinematically redundant 7 DOF manipulator

    NASA Technical Reports Server (NTRS)

    Nguyen, Charles C.; Zhou, Zhen-Lei

    1990-01-01

    The kinematic analysis and control of a kinematically redundant manipulator is addressed. The manipulator is the slave arm of a telerobot system recently built at Goddard Space Flight Center (GSFC) to serve as a testbed for investigating research issues in telerobotics. A forward kinematic transformation is developed in its most simplified form, suitable for real-time control applications, and the manipulator Jacobian is derived using the vector cross product method. Using the developed forward kinematic transformation and quaternion representation of orientation matrices, we perform computer simulation to evaluate the efficiency of the Jacobian in converting joint velocities into Cartesian velocities and to investigate the accuracy of Jacobian pseudo-inverse for various sampling times. The equivalence between Cartesian velocities and quaternion is also verified using computer simulation. Three control schemes are proposed and discussed for controlling the motion of the slave arm end-effector.

  7. REDUNDANT ARRAY CONFIGURATIONS FOR 21 cm COSMOLOGY

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

    Dillon, Joshua S.; Parsons, Aaron R., E-mail: jsdillon@berkeley.edu

    Realizing the potential of 21 cm tomography to statistically probe the intergalactic medium before and during the Epoch of Reionization requires large telescopes and precise control of systematics. Next-generation telescopes are now being designed and built to meet these challenges, drawing lessons from first-generation experiments that showed the benefits of densely packed, highly redundant arrays—in which the same mode on the sky is sampled by many antenna pairs—for achieving high sensitivity, precise calibration, and robust foreground mitigation. In this work, we focus on the Hydrogen Epoch of Reionization Array (HERA) as an interferometer with a dense, redundant core designed followingmore » these lessons to be optimized for 21 cm cosmology. We show how modestly supplementing or modifying a compact design like HERA’s can still deliver high sensitivity while enhancing strategies for calibration and foreground mitigation. In particular, we compare the imaging capability of several array configurations, both instantaneously (to address instrumental and ionospheric effects) and with rotation synthesis (for foreground removal). We also examine the effects that configuration has on calibratability using instantaneous redundancy. We find that improved imaging with sub-aperture sampling via “off-grid” antennas and increased angular resolution via far-flung “outrigger” antennas is possible with a redundantly calibratable array configuration.« less

  8. Redundant Array Configurations for 21 cm Cosmology

    NASA Astrophysics Data System (ADS)

    Dillon, Joshua S.; Parsons, Aaron R.

    2016-08-01

    Realizing the potential of 21 cm tomography to statistically probe the intergalactic medium before and during the Epoch of Reionization requires large telescopes and precise control of systematics. Next-generation telescopes are now being designed and built to meet these challenges, drawing lessons from first-generation experiments that showed the benefits of densely packed, highly redundant arrays—in which the same mode on the sky is sampled by many antenna pairs—for achieving high sensitivity, precise calibration, and robust foreground mitigation. In this work, we focus on the Hydrogen Epoch of Reionization Array (HERA) as an interferometer with a dense, redundant core designed following these lessons to be optimized for 21 cm cosmology. We show how modestly supplementing or modifying a compact design like HERA’s can still deliver high sensitivity while enhancing strategies for calibration and foreground mitigation. In particular, we compare the imaging capability of several array configurations, both instantaneously (to address instrumental and ionospheric effects) and with rotation synthesis (for foreground removal). We also examine the effects that configuration has on calibratability using instantaneous redundancy. We find that improved imaging with sub-aperture sampling via “off-grid” antennas and increased angular resolution via far-flung “outrigger” antennas is possible with a redundantly calibratable array configuration.

  9. Differential involvement of the extracellular 6-O-endosulfatases Sulf1 and Sulf2 in brain development and neuronal and behavioural plasticity

    PubMed Central

    Kalus, Ina; Salmen, Benedikt; Viebahn, Christoph; von Figura, Kurt; Schmitz, Dietmar; D'Hooge, Rudi; Dierks, Thomas

    2009-01-01

    The extracellular sulfatases Sulf1 and Sulf2 remove specific 6-O-sulfate groups from heparan sulfate, thereby modulating numerous signalling pathways underlying development and homeostasis. In vitro data have suggested that the two enzymes show functional redundancy. To elucidate their in vivo functions and to further address the question of a putative redundancy, we have generated Sulf1- and Sulf2-deficient mice. Phenotypic analysis of these animals revealed higher embryonic lethality of Sulf2 knockout mice, which can be associated with neuroanatomical malformations during embryogenesis. Sulf1 seems not to be essential for developmental or postnatal viability, as mice deficient in this sulfatase show no overt phenotype. However, neurite outgrowth deficits were observed in hippocampal and cerebellar neurons of both mutant mouse lines, suggesting that not only Sulf2 but also Sulf1 function plays a role in the developing nervous system. Behavioural analysis revealed differential deficits with regard to cage activity and spatial learning for Sulf1- and Sulf2-deficient mouse lines. In addition, Sulf1-specific deficits were shown for synaptic plasticity in the CA1 region of the hippocampus, associated with a reduced spine density. These results reveal that Sulf1 and Sulf2 fulfil non-redundant functions in vivo in the development and maintenance of the murine nervous system. PMID:20394677

  10. The phylogenetic analysis of tetraspanins projects the evolution of cell-cell interactions from unicellular to multicellular organisms.

    PubMed

    Huang, Shengfeng; Yuan, Shaochun; Dong, Meiling; Su, Jing; Yu, Cuiling; Shen, Yang; Xie, Xiaojin; Yu, Yanhong; Yu, Xuesong; Chen, Shangwu; Zhang, Shicui; Pontarotti, Pierre; Xu, Anlong

    2005-12-01

    In animals, the tetraspanins are a large superfamily of membrane proteins that play important roles in organizing various cell-cell and matrix-cell interactions and signal pathways based on such interactions. However, their origin and evolution largely remain elusive and most of the family's members are functionally unknown or less known due to difficulties of study, such as functional redundancy. In this study, we rebuilt the family's phylogeny with sequences retrieved from online databases and our cDNA library of amphioxus. We reveal that, in addition to in metazoans, various tetraspanins are extensively expressed in protozoan amoebae, fungi, and plants. We also discuss the structural evolution of tetraspanin's major extracellular domain and the relation between tetraspanin's duplication and functional redundancy. Finally, we elucidate the coevolution of tetraspanins and eukaryotes and suggest that tetraspanins play important roles in the unicell-to-multicell transition. In short, the study of tetraspanin in a phylogenetic context helps us understand the evolution of intercellular interactions.

  11. Non-redundant coding of aversive odours in the main olfactory pathway

    PubMed Central

    Dewan, Adam; Pacifico, Rodrigo; Zhan, Ross; Rinberg, Dmitry; Bozza, Thomas

    2013-01-01

    Many species are critically dependent on olfaction for survival. In the main olfactory system of mammals, odours are detected by sensory neurons which express a large repertoire of canonical odorant receptors (ORs) and a much smaller repertoire of Trace Amine-Associated Receptors (TAARs)1–4. Odours are encoded in a combinatorial fashion across glomeruli in the main olfactory bulb, with each glomerulus corresponding to a different receptor5–7. The degree to which individual receptor genes contribute to odour perception is unclear. Here we show that genetic deletion of the olfactory TAAR gene family, or even a single TAAR gene, eliminates aversion that mice display to low concentrations of volatile amines and to the odour of predator urine. Our findings identify a role for the TAARs in olfaction, namely in the high-sensitivity detection of innately aversive odours. In addition, our data reveal that aversive amines are represented in a non-redundant fashion, and that individual main olfactory receptor genes can contribute significantly to odour perception. PMID:23624375

  12. Non-redundant coding of aversive odours in the main olfactory pathway.

    PubMed

    Dewan, Adam; Pacifico, Rodrigo; Zhan, Ross; Rinberg, Dmitry; Bozza, Thomas

    2013-05-23

    Many species are critically dependent on olfaction for survival. In the main olfactory system of mammals, odours are detected by sensory neurons that express a large repertoire of canonical odorant receptors and a much smaller repertoire of trace amine-associated receptors (TAARs). Odours are encoded in a combinatorial fashion across glomeruli in the main olfactory bulb, with each glomerulus corresponding to a specific receptor. The degree to which individual receptor genes contribute to odour perception is unclear. Here we show that genetic deletion of the olfactory Taar gene family, or even a single Taar gene (Taar4), eliminates the aversion that mice display to low concentrations of volatile amines and to the odour of predator urine. Our findings identify a role for the TAARs in olfaction, namely, in the high-sensitivity detection of innately aversive odours. In addition, our data reveal that aversive amines are represented in a non-redundant fashion, and that individual main olfactory receptor genes can contribute substantially to odour perception.

  13. Two enzymes with redundant fructose bisphosphatase activity sustain gluconeogenesis and virulence in Mycobacterium tuberculosis.

    PubMed

    Ganapathy, Uday; Marrero, Joeli; Calhoun, Susannah; Eoh, Hyungjin; de Carvalho, Luiz Pedro Sorio; Rhee, Kyu; Ehrt, Sabine

    2015-08-10

    The human pathogen Mycobacterium tuberculosis (Mtb) likely utilizes host fatty acids as a carbon source during infection. Gluconeogenesis is essential for the conversion of fatty acids into biomass. A rate-limiting step in gluconeogenesis is the conversion of fructose 1,6-bisphosphate to fructose 6-phosphate by a fructose bisphosphatase (FBPase). The Mtb genome contains only one annotated FBPase gene, glpX. Here we show that, unexpectedly, an Mtb mutant lacking GLPX grows on gluconeogenic carbon sources and has detectable FBPase activity. We demonstrate that the Mtb genome encodes an alternative FBPase (GPM2, Rv3214) that can maintain gluconeogenesis in the absence of GLPX. Consequently, deletion of both GLPX and GPM2 is required for disruption of gluconeogenesis and attenuation of Mtb in a mouse model of infection. Our work affirms a role for gluconeogenesis in Mtb virulence and reveals previously unidentified metabolic redundancy at the FBPase-catalysed reaction step of the pathway.

  14. Two enzymes with redundant fructose bisphosphatase activity sustain gluconeogenesis and virulence in Mycobacterium tuberculosis

    PubMed Central

    Ganapathy, Uday; Marrero, Joeli; Calhoun, Susannah; Eoh, Hyungjin; de Carvalho, Luiz Pedro Sorio; Rhee, Kyu; Ehrt, Sabine

    2015-01-01

    The human pathogen Mycobacterium tuberculosis (Mtb) likely utilizes host fatty acids as a carbon source during infection. Gluconeogenesis is essential for the conversion of fatty acids into biomass. A rate-limiting step in gluconeogenesis is the conversion of fructose 1,6-bisphosphate to fructose 6-phosphate by a fructose bisphosphatase (FBPase). The Mtb genome contains only one annotated FBPase gene, glpX. Here we show that, unexpectedly, an Mtb mutant lacking GLPX grows on gluconeogenic carbon sources and has detectable FBPase activity. We demonstrate that the Mtb genome encodes an alternative FBPase (GPM2, Rv3214) that can maintain gluconeogenesis in the absence of GLPX. Consequently, deletion of both GLPX and GPM2 is required for disruption of gluconeogenesis and attenuation of Mtb in a mouse model of infection. Our work affirms a role for gluconeogenesis in Mtb virulence and reveals previously unidentified metabolic redundancy at the FBPase-catalysed reaction step of the pathway. PMID:26258286

  15. Modular pathway engineering of Corynebacterium glutamicum to improve xylose utilization and succinate production.

    PubMed

    Jo, Suah; Yoon, Jinkyung; Lee, Sun-Mi; Um, Youngsoon; Han, Sung Ok; Woo, Han Min

    2017-09-20

    Xylose-negative Corynebacterium glutamicum has been engineered to utilize xylose as the sole carbon source via either the xylose isomerase (XI) pathway or the Weimberg pathway. Heterologous expression of xylose isomerase and overexpression of a gene encoding for xylulose kinase enabled efficient xylose utilization. In this study, we show that two functionally-redundant transcriptional regulators (GntR1 and GntR2) present on xylose repress the pentose phosphate pathway genes. For efficient xylose utilization, pentose phosphate pathway genes and a phosphoketolase gene were overexpressed with the XI pathway in C. glutamicum. Overexpression of the genes encoding for transaldolase (Tal), 6-phosphogluconate dehydrogenase (Gnd), or phosphoketolase (XpkA) enhanced the growth and xylose consumption rates compared to the wild-type with the XI pathway alone. However, co-expression of these genes did not have a synergetic effect on xylose utilization. For the succinate production from xylose, overexpression of the tal gene with the XI pathway in a succinate-producing strain improved xylose utilization and increased the specific succinate production rate by 2.5-fold compared to wild-type with the XI pathway alone. Thus, overexpression of the tal, gnd, or xpkA gene could be helpful for engineering C. glutamicum toward production of value-added chemicals with efficient xylose utilization. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Lessons from applied ecology: cancer control using an evolutionary double bind.

    PubMed

    Gatenby, Robert A; Brown, Joel; Vincent, Thomas

    2009-10-01

    Because the metastatic cascade is largely governed by the ability of malignant cells to adapt and proliferate at the distant tissue site, we propose that disseminated cancers are analogous in many important ways to the evolutionary and ecological dynamics of exotic species. Although pests can be decimated through the application of chemical toxins, this strategy virtually never achieves robust control as evolution of resistant phenotypes typically permits population recovery to pretreatment levels. In general, biological strategies that introduce predators, parasitoids, or pathogens have achieved more durable control of pest populations even after emergence of resistant phenotypes. From this we propose that long term outcome from any treatment strategy for invasive pests, including cancer, is not limited by evolution of resistance, but rather by the phenotypic cost of that resistance. If a cancerous cell's adaptation to therapy is achieved by upregulating xenobiotic metabolism or a redundant signaling pathway, the required investment in resources is small, and the original malignant phenotype remains essentially intact. As a result, the cancer cells' initial high level of fitness is little changed and unconstrained proliferation will resume once resistance evolves. Robust population control is possible if resistance to therapy requires a substantial and costly phenotypic adaptation that also significantly reduces the organism's fitness in its original niche: an evolutionary double bind.

  17. Screening of miRNA profiles and construction of regulation networks in early and late lactation of dairy goat mammary glands.

    PubMed

    Ji, Zhibin; Liu, Zhaohua; Chao, Tianle; Hou, Lei; Fan, Rui; He, Rongyan; Wang, Guizhi; Wang, Jianmin

    2017-09-20

    In recent years, studies related to the expression profiles of miRNAs in the dairy goat mammary gland were performed, but regulatory mechanisms in the physiological environment and the dynamic homeostasis of mammary gland development and lactation are not clear. In the present study, sequencing data analysis of early and late lactation uncovered a total of 1,487 unique miRNAs, including 45 novel miRNA candidates and 1,442 known and conserved miRNAs, of which 758 miRNAs were co-expressed and 378 differentially expressed with P < 0.05. Moreover, 76 non-redundant target genes were annotated in 347 GO consortiums, with 3,143 candidate target genes grouped into 33 pathways. Additionally, 18 predicted target genes of 214 miRNAs were directly annotated in mammary gland development and used to construct regulatory networks based on GO annotation and the KEGG pathway. The expression levels of seven known miRNAs and three novel miRNAs were examined using quantitative real-time PCR. The results showed that miRNAs might play important roles in early and late lactation during dairy goat mammary gland development, which will be helpful to obtain a better understanding of the genetic control of mammary gland lactation and development.

  18. Control Of A Serpentine Robot For Inspection Tasks

    NASA Technical Reports Server (NTRS)

    Seraji, Homayoun; Colbaugh, Richard D.; Glass, Kristin L.

    1996-01-01

    Efficient, robust kinematic control scheme developed to control serpentine robot designed to inspect complex structure. Takes full advantage of multiple redundant degrees of freedom of robot to provide considerable dexterity for maneuvering through workspace cluttered with stationary obstacles at initially unknown positions. Control scheme produces slithering motion.

  19. Phenol and Benzoate Metabolism by Pseudomonas putida: Regulation of Tangential Pathways

    PubMed Central

    Feist, Carol F.; Hegeman, G. D.

    1969-01-01

    Catechol occurs as an intermediate in the metabolism of both benzoate and phenol by strains of Pseudomonas putida. During growth at the expense of benzoate, catechol is cleaved ortho (1,2-oxygenase) and metabolized via the β-ketoadipate pathway; during growth at the expense of phenol or cresols, the catechol or substituted catechols formed are metabolized by a separate pathway following meta (2,3-oxygenase) cleavage of the aromatic ring of catechol. It is possible to explain the mutually exclusive occurrence of the meta and ortho pathway enzymes in phenol- and benzoate-grown cells of P. putida on the basis of differences in the mode of regulation of these two pathways. By use of both nonmetabolizable inducers and blocked mutants, gratuitous synthesis of some of the meta pathway enzymes was obtained. All four enzymes of the meta pathway are induced by the primary substrate, cresol or phenol, or its analogue. Three enzymes of the ortho pathway that catalyze the conversion of catechol to β-ketoadipate enol-lactone are induced by cis,cis-muconate, produced from catechol by 1,2-oxygenase-mediated cleavage. Observations on the differences in specificity of induction and function of the two pathways suggest that they are not really either tangential or redundant. The meta pathway serves as a general mechanism for catabolism of various alkyl derivatives of catechol derived from substituted phenolic compounds. The ortho pathway is more specific and serves primarily in the catabolism of precursors of catechol and catechol itself. PMID:5354952

  20. A real time microcomputer implementation of sensor failure detection for turbofan engines

    NASA Technical Reports Server (NTRS)

    Delaat, John C.; Merrill, Walter C.

    1989-01-01

    An algorithm was developed which detects, isolates, and accommodates sensor failures using analytical redundancy. The performance of this algorithm was demonstrated on a full-scale F100 turbofan engine. The algorithm was implemented in real-time on a microprocessor-based controls computer which includes parallel processing and high order language programming. Parallel processing was used to achieve the required computational power for the real-time implementation. High order language programming was used in order to reduce the programming and maintenance costs of the algorithm implementation software. The sensor failure algorithm was combined with an existing multivariable control algorithm to give a complete control implementation with sensor analytical redundancy. The real-time microprocessor implementation of the algorithm which resulted in the successful completion of the algorithm engine demonstration, is described.

  1. A monitor for the laboratory evaluation of control integrity in digital control systems operating in harsh electromagnetic environments

    NASA Technical Reports Server (NTRS)

    Belcastro, Celeste M.; Fischl, Robert; Kam, Moshe

    1992-01-01

    This paper presents a strategy for dynamically monitoring digital controllers in the laboratory for susceptibility to electromagnetic disturbances that compromise control integrity. The integrity of digital control systems operating in harsh electromagnetic environments can be compromised by upsets caused by induced transient electrical signals. Digital system upset is a functional error mode that involves no component damage, can occur simultaneously in all channels of a redundant control computer, and is software dependent. The motivation for this work is the need to develop tools and techniques that can be used in the laboratory to validate and/or certify critical aircraft controllers operating in electromagnetically adverse environments that result from lightning, high-intensity radiated fields (HIRF), and nuclear electromagnetic pulses (NEMP). The detection strategy presented in this paper provides dynamic monitoring of a given control computer for degraded functional integrity resulting from redundancy management errors, control calculation errors, and control correctness/effectiveness errors. In particular, this paper discusses the use of Kalman filtering, data fusion, and statistical decision theory in monitoring a given digital controller for control calculation errors.

  2. Optimal inventories for overhaul of repairable redundant systems - A Markov decision model

    NASA Technical Reports Server (NTRS)

    Schaefer, M. K.

    1984-01-01

    A Markovian decision model was developed to calculate the optimal inventory of repairable spare parts for an avionics control system for commercial aircraft. Total expected shortage costs, repair costs, and holding costs are minimized for a machine containing a single system of redundant parts. Transition probabilities are calculated for each repair state and repair rate, and optimal spare parts inventory and repair strategies are determined through linear programming. The linear programming solutions are given in a table.

  3. Sensitivity Study for Long Term Reliability

    NASA Technical Reports Server (NTRS)

    White, Allan L.

    2008-01-01

    This paper illustrates using Markov models to establish system and maintenance requirements for small electronic controllers where the goal is a high probability of continuous service for a long period of time. The system and maintenance items considered are quality of components, various degrees of simple redundancy, redundancy with reconfiguration, diagnostic levels, periodic maintenance, and preventive maintenance. Markov models permit a quantitative investigation with comparison and contrast. An element of special interest is the use of conditional probability to study the combination of imperfect diagnostics and periodic maintenance.

  4. Advanced aerodynamics and active controls. Selected NASA research

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Aerodynamic and active control concepts for application to commercial transport aircraft are discussed. Selected topics include in flight direct strike lightning research, triply redundant digital fly by wire control systems, tail configurations, winglets, and the drones for aerodynamic and structural testing (DAST) program.

  5. Use of computer systems and process information for blast furnace operations at U. S. Steel, Gary Works

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

    Sherman, G.J.; Zmierski, M.L.

    1994-09-01

    US Steel Iron Producing Div. consists of four operating blast furnaces ranging in process control capabilities from 1950's and 1960's era hardware to state of the art technology. The oldest control system consists of a large number of panels containing numerous relays, indicating lights, selector switches, push buttons, analog controllers, strip chart recorders and annunciators. In contrast, the state of the art control system utilizes remote I/O, two sets of redundant PLC's, redundant charge director computer, redundant distributed control system, high resolution video-graphic display system and supervisory computer for real-time data acquisition. Process data are collected and archived on twomore » DEC VAX computers, one for No. 13 blast furnace and the other for the three south end furnaces. Historical trending, data analysis and reporting are available to iron producing personnel through terminals and PC's connected directly to the systems, dial-up modems and various network configurations. These two machines are part of the iron producing network which allows them to pass and receive information from each other as well as numerous other sources throughout the division. This configuration allows personnel to access most pertinent furnace information from a single source. The basic objective of the control systems is to charge raw materials to the top of the furnace at aim weights and sequence, while maintaining blast conditions at the bottom of the furnace at required temperature, pressure and composition. Control changes by the operators are primarily supervisory based on review of system generated plots and tables.« less

  6. Verbal redundancy aids memory for filmed entertainment dialogue.

    PubMed

    Hinkin, Michael P; Harris, Richard J; Miranda, Andrew T

    2014-01-01

    Three studies investigated the effects of presentation modality and redundancy of verbal content on recognition memory for entertainment film dialogue. U.S. participants watched two brief movie clips and afterward answered multiple-choice questions about information from the dialogue. Experiment 1 compared recognition memory for spoken dialogue in the native language (English) with subtitles in English, French, or no subtitles. Experiment 2 compared memory for material in English subtitles with spoken dialogue in English, French, or no sound. Experiment 3 examined three control conditions with no spoken or captioned material in the native language. All participants watched the same video clips and answered the same questions. Performance was consistently good whenever English dialogue appeared in either the subtitles or sound, and best of all when it appeared in both, supporting the facilitation of verbal redundancy. Performance was also better when English was only in the subtitles than when it was only spoken. Unexpectedly, sound or subtitles in an unfamiliar language (French) modestly improved performance, as long as there was also a familiar channel. Results extend multimedia research on verbal redundancy for expository material to verbal information in entertainment media.

  7. Control Reconfiguration of Command and Control Systems

    DTIC Science & Technology

    2007-01-01

    decision errors and control action delays upon entering a state. These two undesirable effects can be intertwined. To quantify their individual impact...19 6) Effect of...Study of the Effect of Supervisory Control on a Redundant Database Unit . . . . . . . . . . . . . . 32 (Metzler and Wu, Report to AFRL 2005) 9.1) Problem

  8. Salinity effect on the metabolic pathway and microbial function in phenanthrene degradation by a halophilic consortium.

    PubMed

    Wang, Chongyang; Huang, Yong; Zhang, Zuotao; Wang, Hui

    2018-04-25

    With the close relationship between saline environments and industry, polycyclic aromatic hydrocarbons (PAHs) accumulate in saline/hypersaline environments. Therefore, PAHs degradation by halotolerant/halophilic bacteria has received increasing attention. In this study, the metabolic pathway of phenanthrene degradation by halophilic consortium CY-1 was first studied which showed a single upstream pathway initiated by dioxygenation at the C1 and C2 positions, and at several downstream pathways, including the catechol pathway, gentisic acid pathway and protocatechuic acid pathway. The effects of salinity on the community structure and expression of catabolic genes were further studied by a combination of high-throughput sequencing, catabolic gene clone library and real-time PCR. Pure cultures were also isolated from consortium CY-1 to investigate the contribution made by different microbes in the PAH-degrading process. Marinobacter is the dominant genus that contributed to the upstream degradation of phenanthrene especially in high salt content. Genus Halomonas made a great contribution in transforming intermediates in the subsequent degradation of catechol by using catechol 1,2-dioxygenase (C12O). Other microbes were predicted to be mediating bacteria that were able to utilize intermediates via different downstream pathways. Salinity was investigated to have negative effects on both microbial diversity and activity of consortium CY-1 and consortium CY-1 was found with a high degree of functional redundancy in saline environments.

  9. Adaptive control of nonlinear system using online error minimum neural networks.

    PubMed

    Jia, Chao; Li, Xiaoli; Wang, Kang; Ding, Dawei

    2016-11-01

    In this paper, a new learning algorithm named OEM-ELM (Online Error Minimized-ELM) is proposed based on ELM (Extreme Learning Machine) neural network algorithm and the spreading of its main structure. The core idea of this OEM-ELM algorithm is: online learning, evaluation of network performance, and increasing of the number of hidden nodes. It combines the advantages of OS-ELM and EM-ELM, which can improve the capability of identification and avoid the redundancy of networks. The adaptive control based on the proposed algorithm OEM-ELM is set up which has stronger adaptive capability to the change of environment. The adaptive control of chemical process Continuous Stirred Tank Reactor (CSTR) is also given for application. The simulation results show that the proposed algorithm with respect to the traditional ELM algorithm can avoid network redundancy and improve the control performance greatly. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

  10. On-Line Method and Apparatus for Coordinated Mobility and Manipulation of Mobile Robots

    NASA Technical Reports Server (NTRS)

    Seraji, Homayoun (Inventor)

    1996-01-01

    A simple and computationally efficient approach is disclosed for on-line coordinated control of mobile robots consisting of a manipulator arm mounted on a mobile base. The effect of base mobility on the end-effector manipulability index is discussed. The base mobility and arm manipulation degrees-of-freedom are treated equally as the joints of a kinematically redundant composite robot. The redundancy introduced by the mobile base is exploited to satisfy a set of user-defined additional tasks during the end-effector motion. A simple on-line control scheme is proposed which allows the user to assign weighting factors to individual degrees-of-mobility and degrees-of-manipulation, as well as to each task specification. The computational efficiency of the control algorithm makes it particularly suitable for real-time implementations. Four case studies are discussed in detail to demonstrate the application of the coordinated control scheme to various mobile robots.

  11. Development of a Two-Wheel Contingency Mode for the MAP Spacecraft

    NASA Technical Reports Server (NTRS)

    Starin, Scott R.; ODonnell, James R., Jr.; Bauer, Frank (Technical Monitor)

    2002-01-01

    The Microwave Anisotropy Probe (MAP) is a follow-on mission to the Cosmic Background Explorer (COBE), and is currently collecting data from its orbit near the second Sun-Earth libration point. Due to limited mass, power, and financial resources, a traditional reliability concept including fully redundant components was not feasible for MAP. Instead, the MAP design employs selective hardware redundancy in tandem with contingency software modes and algorithms to improve the odds of mission success. One direction for such improvement has been the development of a two-wheel backup control strategy. This strategy would allow MAP to position itself for maneuvers and collect science data should one of its three reaction wheels fail. Along with operational considerations, the strategy includes three new control algorithms. These algorithms would use the remaining attitude control actuators-thrusters and two reaction wheels-in ways that achieve control goals while minimizing adverse impacts on the functionality of other subsystems and software.

  12. An overview of adaptive model theory: solving the problems of redundancy, resources, and nonlinear interactions in human movement control.

    PubMed

    Neilson, Peter D; Neilson, Megan D

    2005-09-01

    Adaptive model theory (AMT) is a computational theory that addresses the difficult control problem posed by the musculoskeletal system in interaction with the environment. It proposes that the nervous system creates motor maps and task-dependent synergies to solve the problems of redundancy and limited central resources. These lead to the adaptive formation of task-dependent feedback/feedforward controllers able to generate stable, noninteractive control and render nonlinear interactions unobservable in sensory-motor relationships. AMT offers a unified account of how the nervous system might achieve these solutions by forming internal models. This is presented as the design of a simulator consisting of neural adaptive filters based on cerebellar circuitry. It incorporates a new network module that adaptively models (in real time) nonlinear relationships between inputs with changing and uncertain spectral and amplitude probability density functions as is the case for sensory and motor signals.

  13. Fault Detection and Correction for the Solar Dynamics Observatory Attitude Control System

    NASA Technical Reports Server (NTRS)

    Starin, Scott R.; Vess, Melissa F.; Kenney, Thomas M.; Maldonado, Manuel D.; Morgenstern, Wendy M.

    2007-01-01

    The Solar Dynamics Observatory is an Explorer-class mission that will launch in early 2009. The spacecraft will operate in a geosynchronous orbit, sending data 24 hours a day to a devoted ground station in White Sands, New Mexico. It will carry a suite of instruments designed to observe the Sun in multiple wavelengths at unprecedented resolution. The Atmospheric Imaging Assembly includes four telescopes with focal plane CCDs that can image the full solar disk in four different visible wavelengths. The Extreme-ultraviolet Variability Experiment will collect time-correlated data on the activity of the Sun's corona. The Helioseismic and Magnetic Imager will enable study of pressure waves moving through the body of the Sun. The attitude control system on Solar Dynamics Observatory is responsible for four main phases of activity. The physical safety of the spacecraft after separation must be guaranteed. Fine attitude determination and control must be sufficient for instrument calibration maneuvers. The mission science mode requires 2-arcsecond control according to error signals provided by guide telescopes on the Atmospheric Imaging Assembly, one of the three instruments to be carried. Lastly, accurate execution of linear and angular momentum changes to the spacecraft must be provided for momentum management and orbit maintenance. In thsp aper, single-fault tolerant fault detection and correction of the Solar Dynamics Observatory attitude control system is described. The attitude control hardware suite for the mission is catalogued, with special attention to redundancy at the hardware level. Four reaction wheels are used where any three are satisfactory. Four pairs of redundant thrusters are employed for orbit change maneuvers and momentum management. Three two-axis gyroscopes provide full redundancy for rate sensing. A digital Sun sensor and two autonomous star trackers provide two-out-of-three redundancy for fine attitude determination. The use of software to maximize chances of recovery from any hardware or software fault is detailed. A generic fault detection and correction software structure is used, allowing additions, deletions, and adjustments to fault detection and correction rules. This software structure is fed by in-line fault tests that are also able to take appropriate actions to avoid corruption of the data stream.

  14. Robotics technology discipline

    NASA Technical Reports Server (NTRS)

    Montemerlo, Melvin D.

    1990-01-01

    Viewgraphs on robotics technology discipline for Space Station Freedom are presented. Topics covered include: mechanisms; sensors; systems engineering processes for integrated robotics; man/machine cooperative control; 3D-real-time machine perception; multiple arm redundancy control; manipulator control from a movable base; multi-agent reasoning; and surfacing evolution technologies.

  15. A 17 degree of freedom anthropomorphic manipulator

    NASA Technical Reports Server (NTRS)

    Vold, Havard I.; Karlen, James P.; Thompson, Jack M., Jr.; Farrell, James D.; Eismann, Paul H.

    1989-01-01

    A 17 axis anthropomorphic manipulator, providing coordinated control of two seven degree of freedom arms mounted on a three degree of freedom torso-waist assembly, is presented. This massively redundant telerobot, designated the Robotics Research K/B-2017 Dexterous Manipulator, employs a modular mechanism design with joint-mounted actuators based on brushless motors and harmonic drive gear reducers. Direct joint torque control at the servo level causes these high-output joint drives to behave like direct-drive actuators, facilitating the implementation of an effective impedance control scheme. The redundant, but conservative motion control system models the manipulator as a spring-loaded linkage with viscous damping and rotary inertia at each joint. This approach allows for real time, sensor-driven control of manipulator pose using a hierarchy of competing rules, or objective functions, to avoid unplanned collisions with objects in the workplace, to produce energy-efficient, graceful motion, to increase leverage, to control effective impedance at the tool or to favor overloaded joints.

  16. Derivation of three closed loop kinematic velocity models using normalized quaternion feedback for an autonomous redundant manipulator with application to inverse kinematics

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

    Unseren, M.A.

    1993-04-01

    The report discusses the orientation tracking control problem for a kinematically redundant, autonomous manipulator moving in a three dimensional workspace. The orientation error is derived using the normalized quaternion error method of Ickes, the Luh, Walker, and Paul error method, and a method suggested here utilizing the Rodrigues parameters, all of which are expressed in terms of normalized quaternions. The analytical time derivatives of the orientation errors are determined. The latter, along with the translational velocity error, form a dosed loop kinematic velocity model of the manipulator using normalized quaternion and translational position feedback. An analysis of the singularities associatedmore » with expressing the models in a form suitable for solving the inverse kinematics problem is given. Two redundancy resolution algorithms originally developed using an open loop kinematic velocity model of the manipulator are extended to properly take into account the orientation tracking control problem. This report furnishes the necessary mathematical framework required prior to experimental implementation of the orientation tracking control schemes on the seven axis CESARm research manipulator or on the seven-axis Robotics Research K1207i dexterous manipulator, the latter of which is to be delivered to the Oak Ridge National Laboratory in 1993.« less

  17. Intra-axiom redundancies in SNOMED CT.

    PubMed

    Dentler, Kathrin; Cornet, Ronald

    2015-09-01

    Intra-axiom redundancies are elements of concept definitions that are redundant as they are entailed by other elements of the concept definition. While such redundancies are harmless from a logical point of view, they make concept definitions hard to maintain, and they might lead to content-related problems when concepts evolve. The objective of this study is to develop a fully automated method to detect intra-axiom redundancies in OWL 2 EL and apply it to SNOMED Clinical Terms (SNOMED CT). We developed a software program in which we implemented, adapted and extended readily existing rules for redundancy elimination. With this, we analysed occurence of redundancy in 11 releases of SNOMED CT (January 2009 to January 2014). We used the ELK reasoner to classify SNOMED CT, and Pellet for explanation of equivalence. We analysed the completeness and soundness of the results by an in-depth examination of the identified redundant elements in the July 2012 release of SNOMED CT. To determine if concepts with redundant elements lead to maintenance issues, we analysed a small sample of solved redundancies. Analyses showed that the amount of redundantly defined concepts in SNOMED CT is consistently around 35,000. In the July 2012 version of SNOMED CT, 35,010 (12%) of the 296,433 concepts contained redundant elements in their definitions. The results of applying our method are sound and complete with respect to our evaluation. Analysis of solved redundancies suggests that redundancies in concept definitions lead to inadequate maintenance of SNOMED CT. Our analysis revealed that redundant elements are continuously introduced and removed, and that redundant elements may be overlooked when concept definitions are corrected. Applying our redundancy detection method to remove intra-axiom redundancies from the stated form of SNOMED CT and to point knowledge modellers to newly introduced redundancies can support creating and maintaining a redundancy-free version of SNOMED CT. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Modelling and performance analysis of clinical pathways using the stochastic process algebra PEPA.

    PubMed

    Yang, Xian; Han, Rui; Guo, Yike; Bradley, Jeremy; Cox, Benita; Dickinson, Robert; Kitney, Richard

    2012-01-01

    Hospitals nowadays have to serve numerous patients with limited medical staff and equipment while maintaining healthcare quality. Clinical pathway informatics is regarded as an efficient way to solve a series of hospital challenges. To date, conventional research lacks a mathematical model to describe clinical pathways. Existing vague descriptions cannot fully capture the complexities accurately in clinical pathways and hinders the effective management and further optimization of clinical pathways. Given this motivation, this paper presents a clinical pathway management platform, the Imperial Clinical Pathway Analyzer (ICPA). By extending the stochastic model performance evaluation process algebra (PEPA), ICPA introduces a clinical-pathway-specific model: clinical pathway PEPA (CPP). ICPA can simulate stochastic behaviours of a clinical pathway by extracting information from public clinical databases and other related documents using CPP. Thus, the performance of this clinical pathway, including its throughput, resource utilisation and passage time can be quantitatively analysed. A typical clinical pathway on stroke extracted from a UK hospital is used to illustrate the effectiveness of ICPA. Three application scenarios are tested using ICPA: 1) redundant resources are identified and removed, thus the number of patients being served is maintained with less cost; 2) the patient passage time is estimated, providing the likelihood that patients can leave hospital within a specific period; 3) the maximum number of input patients are found, helping hospitals to decide whether they can serve more patients with the existing resource allocation. ICPA is an effective platform for clinical pathway management: 1) ICPA can describe a variety of components (state, activity, resource and constraints) in a clinical pathway, thus facilitating the proper understanding of complexities involved in it; 2) ICPA supports the performance analysis of clinical pathway, thereby assisting hospitals to effectively manage time and resources in clinical pathway.

  19. Control algorithm implementation for a redundant degree of freedom manipulator

    NASA Technical Reports Server (NTRS)

    Cohan, Steve

    1991-01-01

    This project's purpose is to develop and implement control algorithms for a kinematically redundant robotic manipulator. The manipulator is being developed concurrently by Odetics Inc., under internal research and development funding. This SBIR contract supports algorithm conception, development, and simulation, as well as software implementation and integration with the manipulator hardware. The Odetics Dexterous Manipulator is a lightweight, high strength, modular manipulator being developed for space and commercial applications. It has seven fully active degrees of freedom, is electrically powered, and is fully operational in 1 G. The manipulator consists of five self-contained modules. These modules join via simple quick-disconnect couplings and self-mating connectors which allow rapid assembly/disassembly for reconfiguration, transport, or servicing. Each joint incorporates a unique drive train design which provides zero backlash operation, is insensitive to wear, and is single fault tolerant to motor or servo amplifier failure. The sensing system is also designed to be single fault tolerant. Although the initial prototype is not space qualified, the design is well-suited to meeting space qualification requirements. The control algorithm design approach is to develop a hierarchical system with well defined access and interfaces at each level. The high level endpoint/configuration control algorithm transforms manipulator endpoint position/orientation commands to joint angle commands, providing task space motion. At the same time, the kinematic redundancy is resolved by controlling the configuration (pose) of the manipulator, using several different optimizing criteria. The center level of the hierarchy servos the joints to their commanded trajectories using both linear feedback and model-based nonlinear control techniques. The lowest control level uses sensed joint torque to close torque servo loops, with the goal of improving the manipulator dynamic behavior. The control algorithms are subjected to a dynamic simulation before implementation.

  20. Coresets vs clustering: comparison of methods for redundancy reduction in very large white matter fiber sets

    NASA Astrophysics Data System (ADS)

    Alexandroni, Guy; Zimmerman Moreno, Gali; Sochen, Nir; Greenspan, Hayit

    2016-03-01

    Recent advances in Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) of white matter in conjunction with improved tractography produce impressive reconstructions of White Matter (WM) pathways. These pathways (fiber sets) often contain hundreds of thousands of fibers, or more. In order to make fiber based analysis more practical, the fiber set needs to be preprocessed to eliminate redundancies and to keep only essential representative fibers. In this paper we demonstrate and compare two distinctive frameworks for selecting this reduced set of fibers. The first framework entails pre-clustering the fibers using k-means, followed by Hierarchical Clustering and replacing each cluster with one representative. For the second clustering stage seven distance metrics were evaluated. The second framework is based on an efficient geometric approximation paradigm named coresets. Coresets present a new approach to optimization and have huge success especially in tasks requiring large computation time and/or memory. We propose a modified version of the coresets algorithm, Density Coreset. It is used for extracting the main fibers from dense datasets, leaving a small set that represents the main structures and connectivity of the brain. A novel approach, based on a 3D indicator structure, is used for comparing the frameworks. This comparison was applied to High Angular Resolution Diffusion Imaging (HARDI) scans of 4 healthy individuals. We show that among the clustering based methods, that cosine distance gives the best performance. In comparing the clustering schemes with coresets, Density Coreset method achieves the best performance.

  1. Requirement and Redundancy of the Src Family Kinases Fyn and Lyn in Perforin-Dependent Killing of Cryptococcus neoformans by NK Cells

    PubMed Central

    Oykhman, Paul; Timm-McCann, Martina; Xiang, Richard F.; Islam, Anowara; Li, Shu Shun; Stack, Danuta; Huston, Shaunna M.; Ma, Ling Ling

    2013-01-01

    Natural killer (NK) cells directly recognize and kill fungi, such as the pathogenic fungus Cryptococcus neoformans, via cytolytic mechanisms. However, the precise signaling pathways governing this NK cell microbicidal activity and the implications for fungal recognition are still unknown. Previously, it was reported that NK cell anticryptococcal activity is mediated through a conserved phosphatidylinositol 3-kinase–extracellular signal-regulated kinase 1/2 (PI3K-ERK1/2) pathway. Using YT (a human NK-like cell line) and primary human NK cells, we sought to identify the upstream, receptor-proximal signaling elements that led to fungal cytolysis. We demonstrate that Src family kinases were activated in response to C. neoformans. Furthermore, pharmacologic inhibition with an Src kinase inhibitor blocked C. neoformans-induced downstream activation of PI3K and ERK1/2 and abrogated cryptococcal killing. At the same time, the inhibitor disrupted the polarization of perforin-containing granules toward the NK cell-cryptococcal synapse but had no effect on conjugate formation between the organism and the NK cell. Finally, small interfering RNA (siRNA) double (but not single) knockdown of two Src family kinases, Fyn and Lyn, blocked cryptococcal killing. Together these data demonstrate a mechanism whereby the Src family kinases, Fyn and Lyn, redundantly mediate anticryptococcal activity through the activation of PI3K and ERK1/2, which in turn facilitates killing by inducing the polarization of perforin-containing granules to the NK cell-cryptococcal synapse. PMID:23918783

  2. Hybrid online sensor error detection and functional redundancy for systems with time-varying parameters.

    PubMed

    Feng, Jianyuan; Turksoy, Kamuran; Samadi, Sediqeh; Hajizadeh, Iman; Littlejohn, Elizabeth; Cinar, Ali

    2017-12-01

    Supervision and control systems rely on signals from sensors to receive information to monitor the operation of a system and adjust manipulated variables to achieve the control objective. However, sensor performance is often limited by their working conditions and sensors may also be subjected to interference by other devices. Many different types of sensor errors such as outliers, missing values, drifts and corruption with noise may occur during process operation. A hybrid online sensor error detection and functional redundancy system is developed to detect errors in online signals, and replace erroneous or missing values detected with model-based estimates. The proposed hybrid system relies on two techniques, an outlier-robust Kalman filter (ORKF) and a locally-weighted partial least squares (LW-PLS) regression model, which leverage the advantages of automatic measurement error elimination with ORKF and data-driven prediction with LW-PLS. The system includes a nominal angle analysis (NAA) method to distinguish between signal faults and large changes in sensor values caused by real dynamic changes in process operation. The performance of the system is illustrated with clinical data continuous glucose monitoring (CGM) sensors from people with type 1 diabetes. More than 50,000 CGM sensor errors were added to original CGM signals from 25 clinical experiments, then the performance of error detection and functional redundancy algorithms were analyzed. The results indicate that the proposed system can successfully detect most of the erroneous signals and substitute them with reasonable estimated values computed by functional redundancy system.

  3. Quality Assurance of RNA Expression Profiling in Clinical Laboratories

    PubMed Central

    Tang, Weihua; Hu, Zhiyuan; Muallem, Hind; Gulley, Margaret L.

    2012-01-01

    RNA expression profiles are increasingly used to diagnose and classify disease, based on expression patterns of as many as several thousand RNAs. To ensure quality of expression profiling services in clinical settings, a standard operating procedure incorporates multiple quality indicators and controls, beginning with preanalytic specimen preparation and proceeding thorough analysis, interpretation, and reporting. Before testing, histopathological examination of each cellular specimen, along with optional cell enrichment procedures, ensures adequacy of the input tissue. Other tactics include endogenous controls to evaluate adequacy of RNA and exogenous or spiked controls to evaluate run- and patient-specific performance of the test system, respectively. Unique aspects of quality assurance for array-based tests include controls for the pertinent outcome signatures that often supersede controls for each individual analyte, built-in redundancy for critical analytes or biochemical pathways, and software-supported scrutiny of abundant data by a laboratory physician who interprets the findings in a manner facilitating appropriate medical intervention. Access to high-quality reagents, instruments, and software from commercial sources promotes standardization and adoption in clinical settings, once an assay is vetted in validation studies as being analytically sound and clinically useful. Careful attention to the well-honed principles of laboratory medicine, along with guidance from government and professional groups on strategies to preserve RNA and manage large data sets, promotes clinical-grade assay performance. PMID:22020152

  4. The Maintenance of Mitochondrial DNA Integrity—Critical Analysis and Update

    PubMed Central

    Alexeyev, Mikhail; Shokolenko, Inna; Wilson, Glenn; LeDoux, Susan

    2013-01-01

    DNA molecules in mitochondria, just like those in the nucleus of eukaryotic cells, are constantly damaged by noxious agents. Eukaryotic cells have developed efficient mechanisms to deal with this assault. The process of DNA repair in mitochondria, initially believed nonexistent, has now evolved into a mature area of research. In recent years, it has become increasingly appreciated that mitochondria possess many of the same DNA repair pathways that the nucleus does. Moreover, a unique pathway that is enabled by high redundancy of the mitochondrial DNA and allows for the disposal of damaged DNA molecules operates in this organelle. In this review, we attempt to present a unified view of our current understanding of the process of DNA repair in mitochondria with an emphasis on issues that appear controversial. PMID:23637283

  5. Integrated Application of Active Controls (IAAC) technology to an advanced subsonic transport project: Current and advanced act control system definition study, volume 1

    NASA Technical Reports Server (NTRS)

    Hanks, G. W.; Shomber, H. A.; Dethman, H. A.; Gratzer, L. B.; Maeshiro, A.; Gangsaas, D.; Blight, J. D.; Buchan, S. M.; Crumb, C. B.; Dorwart, R. J.

    1981-01-01

    An active controls technology (ACT) system architecture was selected based on current technology system elements and optimal control theory was evaluated for use in analyzing and synthesizing ACT multiple control laws. The system selected employs three redundant computers to implement all of the ACT functions, four redundant smaller computers to implement the crucial pitch-augmented stability function, and a separate maintenance and display computer. The reliability objective of probability of crucial function failure of less than 1 x 10 to the -9th power per flight of 1 hr can be met with current technology system components, if the software is assumed fault free and coverage approaching 1.0 can be provided. The optimal control theory approach to ACT control law synthesis yielded comparable control law performance much more systematically and directly than the classical s-domain approach. The ACT control law performance, although somewhat degraded by the inclusion of representative nonlinearities, remained quite effective. Certain high-frequency gust-load alleviation functions may require increased surface rate capability.

  6. Local performance optimization for a class of redundant eight-degree-of-freedom manipulators

    NASA Technical Reports Server (NTRS)

    Williams, Robert L., II

    1994-01-01

    Local performance optimization for joint limit avoidance and manipulability maximization (singularity avoidance) is obtained by using the Jacobian matrix pseudoinverse and by projecting the gradient of an objective function into the Jacobian null space. Real-time redundancy optimization control is achieved for an eight-joint redundant manipulator having a three-axis spherical shoulder, a single elbow joint, and a four-axis spherical wrist. Symbolic solutions are used for both full-Jacobian and wrist-partitioned pseudoinverses, partitioned null-space projection matrices, and all objective function gradients. A kinematic limitation of this class of manipulators and the limitation's effect on redundancy resolution are discussed. Results obtained with graphical simulation are presented to demonstrate the effectiveness of local redundant manipulator performance optimization. Actual hardware experiments performed to verify the simulated results are also discussed. A major result is that the partitioned solution is desirable because of low computation requirements. The partitioned solution is suboptimal compared with the full solution because translational and rotational terms are optimized separately; however, the results show that the difference is not significant. Singularity analysis reveals that no algorithmic singularities exist for the partitioned solution. The partitioned and full solutions share the same physical manipulator singular conditions. When compared with the full solution, the partitioned solution is shown to be ill-conditioned in smaller neighborhoods of the shared singularities.

  7. The Use of Gene Ontology Term and KEGG Pathway Enrichment for Analysis of Drug Half-Life

    PubMed Central

    Chen, Lei; Lu, Jing; Kong, XiangYin; Huang, Tao; Li, HaiPeng

    2016-01-01

    A drug’s biological half-life is defined as the time required for the human body to metabolize or eliminate 50% of the initial drug dosage. Correctly measuring the half-life of a given drug is helpful for the safe and accurate usage of the drug. In this study, we investigated which gene ontology (GO) terms and biological pathways were highly related to the determination of drug half-life. The investigated drugs, with known half-lives, were analyzed based on their enrichment scores for associated GO terms and KEGG pathways. These scores indicate which GO terms or KEGG pathways the drug targets. The feature selection method, minimum redundancy maximum relevance, was used to analyze these GO terms and KEGG pathways and to identify important GO terms and pathways, such as sodium-independent organic anion transmembrane transporter activity (GO:0015347), monoamine transmembrane transporter activity (GO:0008504), negative regulation of synaptic transmission (GO:0050805), neuroactive ligand-receptor interaction (hsa04080), serotonergic synapse (hsa04726), and linoleic acid metabolism (hsa00591), among others. This analysis confirmed our results and may show evidence for a new method in studying drug half-lives and building effective computational methods for the prediction of drug half-lives. PMID:27780226

  8. Mobility and Position Error Analysis of a Complex Planar Mechanism with Redundant Constraints

    NASA Astrophysics Data System (ADS)

    Sun, Qipeng; Li, Gangyan

    2018-03-01

    Nowadays mechanisms with redundant constraints have been created and attracted much attention for their merits. The mechanism of the redundant constraints in a mechanical system is analyzed in this paper. A analysis method of Planar Linkage with a repetitive structure is proposed to get the number and type of constraints. According to the difference of applications and constraint characteristics, the redundant constraints are divided into the theoretical planar redundant constraints and the space-planar redundant constraints. And the calculation formula for the number of redundant constraints and type of judging method are carried out. And a complex mechanism with redundant constraints is analyzed of the influence about redundant constraints on mechanical performance. With the combination of theoretical derivation and simulation research, a mechanism analysis method is put forward about the position error of complex mechanism with redundant constraints. It points out the direction on how to eliminate or reduce the influence of redundant constraints.

  9. Parallels between UNUSUAL FLORAL ORGANS and FIMBRIATA, genes controlling flower development in Arabidopsis and Antirrhinum.

    PubMed

    Ingram, G C; Goodrich, J; Wilkinson, M D; Simon, R; Haughn, G W; Coen, E S

    1995-09-01

    The unusual floral organs (ufo) mutant of Arabidopsis has flowers with variable homeotic organ transformations and inflorescence-like characteristics. To determine the relationship between UFO and previously characterized meristem and organ identity genes, we cloned UFO and determined its expression pattern. The UFO gene shows extensive homology with FIMBRIATA (FIM), a gene mediating between meristem and organ identity genes in Antirrhinum. All three UFO mutant alleles that we sequenced are predicted to produce truncated proteins. UFO transcripts were first detected in early floral meristems, before organ identity genes had been activated. At later developmental stages, UFO expression is restricted to the junction between sepal and petal primordia. Phenotypic, genetic, and expression pattern comparisons between UFO and FIM suggest that they are cognate homologs and play a similar role in mediating between meristem and organ identity genes. However, some differences in the functions and genetic interactions of UFO and FIM were apparent, indicating that changes in partially redundant pathways have occurred during the evolutionary divergence of Arabidopsis and Antirrhinum.

  10. An evaluation plan of bus architectures and protocols using the NASA Ames intelligent redundant actuation system

    NASA Technical Reports Server (NTRS)

    Defeo, P.; Chen, M.

    1987-01-01

    Means for evaluating data bus architectures and protocols for highly integrated flight control system applications are needed. Described are the criteria and plans to do this by using the NASA/Ames Intelligent Redundant Actuation System (IRAS) experimental set-up. Candidate bus architectures differ from one another in terms of: topology, access control, message transfer schemes, message characteristics, initialization. data flow control, transmission rates, fault tolerance, and time synchronization. The evaluation criteria are developed relative to these features. A preliminary, analytical evaluation of four candidate busses (MIL-STD-1553B, DATAC, Ethernet, and HSIS) is described. A bus must be exercised in a real-time environment to evaluate its dynamic characteristics. A plan for real-time evaluation of these four busses using a combination of hardware and simulation techniques is presented.

  11. On reliable control system designs. Ph.D. Thesis; [actuators

    NASA Technical Reports Server (NTRS)

    Birdwell, J. D.

    1978-01-01

    A mathematical model for use in the design of reliable multivariable control systems is discussed with special emphasis on actuator failures and necessary actuator redundancy levels. The model consists of a linear time invariant discrete time dynamical system. Configuration changes in the system dynamics are governed by a Markov chain that includes transition probabilities from one configuration state to another. The performance index is a standard quadratic cost functional, over an infinite time interval. The actual system configuration can be deduced with a one step delay. The calculation of the optimal control law requires the solution of a set of highly coupled Riccati-like matrix difference equations. Results can be used for off-line studies relating the open loop dynamics, required performance, actuator mean time to failure, and functional or identical actuator redundancy, with and without feedback gain reconfiguration strategies.

  12. Task constraints and minimization of muscle effort result in a small number of muscle synergies during gait.

    PubMed

    De Groote, Friedl; Jonkers, Ilse; Duysens, Jacques

    2014-01-01

    Finding muscle activity generating a given motion is a redundant problem, since there are many more muscles than degrees of freedom. The control strategies determining muscle recruitment from a redundant set are still poorly understood. One theory of motor control suggests that motion is produced through activating a small number of muscle synergies, i.e., muscle groups that are activated in a fixed ratio by a single input signal. Because of the reduced number of input signals, synergy-based control is low dimensional. But a major criticism on the theory of synergy-based control of muscles is that muscle synergies might reflect task constraints rather than a neural control strategy. Another theory of motor control suggests that muscles are recruited by optimizing performance. Optimization of performance has been widely used to calculate muscle recruitment underlying a given motion while assuming independent recruitment of muscles. If synergies indeed determine muscle recruitment underlying a given motion, optimization approaches that do not model synergy-based control could result in muscle activations that do not show the synergistic muscle action observed through electromyography (EMG). If, however, synergistic muscle action results from performance optimization and task constraints (joint kinematics and external forces), such optimization approaches are expected to result in low-dimensional synergistic muscle activations that are similar to EMG-based synergies. We calculated muscle recruitment underlying experimentally measured gait patterns by optimizing performance assuming independent recruitment of muscles. We found that the muscle activations calculated without any reference to synergies can be accurately explained by on average four synergies. These synergies are similar to EMG-based synergies. We therefore conclude that task constraints and performance optimization explain synergistic muscle recruitment from a redundant set of muscles.

  13. Pathways to extinction: beyond the error threshold.

    PubMed

    Manrubia, Susanna C; Domingo, Esteban; Lázaro, Ester

    2010-06-27

    Since the introduction of the quasispecies and the error catastrophe concepts for molecular evolution by Eigen and their subsequent application to viral populations, increased mutagenesis has become a common strategy to cause the extinction of viral infectivity. Nevertheless, the high complexity of virus populations has shown that viral extinction can occur through several other pathways apart from crossing an error threshold. Increases in the mutation rate enhance the appearance of defective forms and promote the selection of mechanisms that are able to counteract the accelerated appearance of mutations. Current models of viral evolution take into account more realistic scenarios that consider compensatory and lethal mutations, a highly redundant genotype-to-phenotype map, rough fitness landscapes relating phenotype and fitness, and where phenotype is described as a set of interdependent traits. Further, viral populations cannot be understood without specifying the characteristics of the environment where they evolve and adapt. Altogether, it turns out that the pathways through which viral quasispecies go extinct are multiple and diverse.

  14. Language Learning Variability within the Dorsal and Ventral Streams as a Cue for Compensatory Mechanisms in Aphasia Recovery

    PubMed Central

    López-Barroso, Diana; de Diego-Balaguer, Ruth

    2017-01-01

    Dorsal and ventral pathways connecting perisylvian language areas have been shown to be functionally and anatomically segregated. Whereas the dorsal pathway integrates the sensory-motor information required for verbal repetition, the ventral pathway has classically been associated with semantic processes. The great individual differences characterizing language learning through life partly correlate with brain structure and function within these dorsal and ventral language networks. Variability and plasticity within these networks also underlie inter-individual differences in the recovery of linguistic abilities in aphasia. Despite the division of labor of the dorsal and ventral streams, studies in healthy individuals have shown how the interaction of them and the redundancy in the areas they connect allow for compensatory strategies in functions that are usually segregated. In this mini-review we highlight the need to examine compensatory mechanisms between streams in healthy individuals as a helpful guide to choosing the most appropriate rehabilitation strategies, using spared functions and targeting preserved compensatory networks for brain plasticity. PMID:29021751

  15. Techniques and potential capabilities of multi-resolutional information (knowledge) processing

    NASA Technical Reports Server (NTRS)

    Meystel, A.

    1989-01-01

    A concept of nested hierarchical (multi-resolutional, pyramidal) information (knowledge) processing is introduced for a variety of systems including data and/or knowledge bases, vision, control, and manufacturing systems, industrial automated robots, and (self-programmed) autonomous intelligent machines. A set of practical recommendations is presented using a case study of a multiresolutional object representation. It is demonstrated here that any intelligent module transforms (sometimes, irreversibly) the knowledge it deals with, and this tranformation affects the subsequent computation processes, e.g., those of decision and control. Several types of knowledge transformation are reviewed. Definite conditions are analyzed, satisfaction of which is required for organization and processing of redundant information (knowledge) in the multi-resolutional systems. Providing a definite degree of redundancy is one of these conditions.

  16. Evolution of shuttle avionics redundancy management/fault tolerance

    NASA Technical Reports Server (NTRS)

    Boykin, J. C.; Thibodeau, J. R.; Schneider, H. E.

    1985-01-01

    The challenge of providing redundancy management (RM) and fault tolerance to meet the Shuttle Program requirements of fail operational/fail safe for the avionics systems was complicated by the critical program constraints of weight, cost, and schedule. The basic and sometimes false effectivity of less than pure RM designs is addressed. Evolution of the multiple input selection filter (the heart of the RM function) is discussed with emphasis on the subtle interactions of the flight control system that were found to be potentially catastrophic. Several other general RM development problems are discussed, with particular emphasis on the inertial measurement unit RM, indicative of the complexity of managing that three string system and its critical interfaces with the guidance and control systems.

  17. Redundant manipulator techniques for partially decentralized path planning and control of a platoon of autonomous vehicles.

    PubMed

    Stilwell, Daniel J; Bishop, Bradley E; Sylvester, Caleb A

    2005-08-01

    An approach to real-time trajectory generation for platoons of autonomous vehicles is developed from well-known control techniques for redundant robotic manipulators. The partially decentralized structure of this approach permits each vehicle to independently compute its trajectory in real-time using only locally generated information and low-bandwidth feedback generated by a system exogenous to the platoon. Our work is motivated by applications for which communications bandwidth is severely limited, such for platoons of autonomous underwater vehicles. The communication requirements for our trajectory generation approach are independent of the number of vehicles in the platoon, enabling platoons composed of a large number of vehicles to be coordinated despite limited communication bandwidth.

  18. Phytochrome regulation of cellulose synthesis in Arabidopsis.

    PubMed

    Bischoff, Volker; Desprez, Thierry; Mouille, Gregory; Vernhettes, Samantha; Gonneau, Martine; Höfte, Herman

    2011-11-08

    Plant development is highly plastic and dependent on light quantity and quality monitored by specific photoreceptors. Although we have a detailed knowledge of light signaling pathways, little is known about downstream targets involved in growth control. Cell size and shape are in part controlled by cellulose microfibrils extruded from large cellulose synthase complexes (CSCs) that migrate in the plasma membrane along cortical microtubules. Here we show a role for the red/far-red light photoreceptor PHYTOCHROME B (PHYB) in the regulation of cellulose synthesis in the growing Arabidopsis hypocotyl. In this organ, CSCs contains three distinct cellulose synthase (CESA) isoform classes: nonredundant CESA1 and CESA3 and a third class represented by partially redundant CESA2, CESA5, and CESA6. Interestingly, in the dark, depending on which CESA subunits occupy the third position, CSC velocity is more or less inhibited through an interaction with microtubules. Activation of PHYB overrules this inhibition. The analysis of cesa5 mutants shows a role for phosphorylation in the control of CSC velocity. These results, combined with the cesa5 mutant phenotype, suggest that cellulose synthesis is fine tuned through the regulated interaction of CSCs with microtubules and that PHYB signaling impinges on this process to maintain cell wall strength and growth in changing environments. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. 78 FR 20236 - Self-Regulation of Class II Gaming

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-04

    ... commenters also submitted that this requirement is redundant, because tribal internal control systems (TICS... tribe should have readily available a list of internal gaming controls, which is a useful tool in.... 518.4(c)(vii), which requires petitioning tribes to submit a list of internal controls used at the...

  20. Control of large flexible space structures

    NASA Technical Reports Server (NTRS)

    Vandervelde, W. E.

    1986-01-01

    Progress in robust design of generalized parity relations, design of failure sensitive observers using the geometric system theory of Wonham, computational techniques for evaluation of the performance of control systems with fault tolerance and redundancy management features, and the design and evaluation od control systems for structures having nonlinear joints are described.

  1. Error Control Coding Techniques for Space and Satellite Communications

    NASA Technical Reports Server (NTRS)

    Costello, Daniel J., Jr.; Cabral, Hermano A.; He, Jiali

    1997-01-01

    Bootstrap Hybrid Decoding (BHD) (Jelinek and Cocke, 1971) is a coding/decoding scheme that adds extra redundancy to a set of convolutionally encoded codewords and uses this redundancy to provide reliability information to a sequential decoder. Theoretical results indicate that bit error probability performance (BER) of BHD is close to that of Turbo-codes, without some of their drawbacks. In this report we study the use of the Multiple Stack Algorithm (MSA) (Chevillat and Costello, Jr., 1977) as the underlying sequential decoding algorithm in BHD, which makes possible an iterative version of BHD.

  2. Gluconeogenesis in Leishmania mexicana

    PubMed Central

    Rodriguez-Contreras, Dayana; Hamilton, Nicklas

    2014-01-01

    Gluconeogenesis is an active pathway in Leishmania amastigotes and is essential for their survival within the mammalian cells. However, our knowledge about this pathway in trypanosomatids is very limited. We investigated the role of glycerol kinase (GK), phosphoenolpyruvate carboxykinase (PEPCK), and pyruvate phosphate dikinase (PPDK) in gluconeogenesis by generating the respective Leishmania mexicana Δgk, Δpepck, and Δppdk null mutants. Our results demonstrated that indeed GK, PEPCK, and PPDK are key players in the gluconeogenesis pathway in Leishmania, although stage-specific differences in their contribution to this pathway were found. GK participates in the entry of glycerol in promastigotes and amastigotes; PEPCK participates in the entry of aspartate in promastigotes, and PPDK is involved in the entry of alanine in amastigotes. Furthermore, the majority of alanine enters into the pathway via decarboxylation of pyruvate in promastigotes, whereas pathway redundancy is suggested for the entry of aspartate in amastigotes. Interestingly, we also found that l-lactate, an abundant glucogenic precursor in mammals, was used by Leishmania amastigotes to synthesize mannogen, entering the pathway through PPDK. On the basis of these new results, we propose a revision in the current model of gluconeogenesis in Leishmania, emphasizing the differences between amastigotes and promastigotes. This work underlines the importance of studying the trypanosomatid intracellular life cycle stages to gain a better understanding of the pathologies caused in humans. PMID:25288791

  3. Programed asynchronous serial data interrogation in a two-computer system

    NASA Technical Reports Server (NTRS)

    Schneberger, N. A.

    1975-01-01

    Technique permits redundant computers, with one unit in control mode and one in MONITOR mode, to interrogate the same serial data source. Its use for program-controlled serial data transfer results in extremely simple hardware and software mechanization.

  4. Phosphoproteomic Analysis of Protein Kinase C Signaling in Saccharomyces cerevisiae Reveals Slt2 Mitogen-activated Protein Kinase (MAPK)-dependent Phosphorylation of Eisosome Core Components*

    PubMed Central

    Mascaraque, Victoria; Hernáez, María Luisa; Jiménez-Sánchez, María; Hansen, Rasmus; Gil, Concha; Martín, Humberto; Cid, Víctor J.; Molina, María

    2013-01-01

    The cell wall integrity (CWI) pathway of the model organism Saccharomyces cerevisiae has been thoroughly studied as a paradigm of the mitogen-activated protein kinase (MAPK) pathway. It consists of a classic MAPK module comprising the Bck1 MAPK kinase kinase, two redundant MAPK kinases (Mkk1 and Mkk2), and the Slt2 MAPK. This module is activated under a variety of stimuli related to cell wall homeostasis by Pkc1, the only member of the protein kinase C family in budding yeast. Quantitative phosphoproteomics based on stable isotope labeling of amino acids in cell culture is a powerful tool for globally studying protein phosphorylation. Here we report an analysis of the yeast phosphoproteome upon overexpression of a PKC1 hyperactive allele that specifically activates CWI MAPK signaling in the absence of external stimuli. We found 82 phosphopeptides originating from 43 proteins that showed enhanced phosphorylation in these conditions. The MAPK S/T-P target motif was significantly overrepresented in these phosphopeptides. Hyperphosphorylated proteins provide putative novel targets of the Pkc1–cell wall integrity pathway involved in diverse functions such as the control of gene expression, protein synthesis, cytoskeleton maintenance, DNA repair, and metabolism. Remarkably, five components of the plasma-membrane-associated protein complex known as eisosomes were found among the up-regulated proteins. We show here that Pkc1-induced phosphorylation of the eisosome core components Pil1 and Lsp1 was not exerted directly by Pkc1, but involved signaling through the Slt2 MAPK module. PMID:23221999

  5. Learners misperceive the benefits of redundant text in multimedia learning.

    PubMed

    Fenesi, Barbara; Kim, Joseph A

    2014-01-01

    Research on metacognition has consistently demonstrated that learners fail to endorse instructional designs that produce benefits to memory, and often prefer designs that actually impair comprehension. Unlike previous studies in which learners were only exposed to a single multimedia design, the current study used a within-subjects approach to examine whether exposure to both redundant text and non-redundant text multimedia presentations improved learners' metacognitive judgments about presentation styles that promote better understanding. A redundant text multimedia presentation containing narration paired with verbatim on-screen text (Redundant) was contrasted with two non-redundant text multimedia presentations: (1) narration paired with images and minimal text (Complementary) or (2) narration paired with minimal text (Sparse). Learners watched presentation pairs of either Redundant + Complementary, or Redundant + Sparse. Results demonstrate that Complementary and Sparse presentations produced highest overall performance on the final comprehension assessment, but the Redundant presentation produced highest perceived understanding and engagement ratings. These findings suggest that learners misperceive the benefits of redundant text, even after direct exposure to a non-redundant, effective presentation.

  6. Leptin and Reproduction: Past Milestones, Present Undertakings and Future Endeavors

    PubMed Central

    Chehab, Farid F.

    2014-01-01

    The association between leptin and reproduction originated with the leptin-mediated correction of sterility in ob/ob mice and initiation of reproductive function in normal female mice. The uncovering of a central leptin pathway regulating food intake prompted the dissection of neuroendocrine mechanisms involving leptin in the metabolic control of reproduction. The absence of leptin receptors on GnRH neurons incited a search for intermediary neurons situated between leptin responsive and GnRH neurons. This review addresses the most significant findings that have furthered our understanding of recent progress in this new field. The role of leptin in puberty was impacted by the discovery of neurons that co-express kisspeptin, neurokinin B and dynorphin and that could act as leptin intermediates. Furthermore, the identification of first-order leptin-responsive neurons in the premammilary ventral nucleus and other brain regions opens new avenues to explore their relationship to GnRH neurons. Central to these advances is the unveiling that AgRP/NPY neurons project onto GnRH and kisspeptin neurons, allowing a crosstalk between food intake and reproduction. Finally, whereas puberty is a state of leptin sensitivity, mid-gestation represents a state of leptin resistance aimed at building energy stores to sustain pregnancy and lactation. Mechanisms underlying leptin resistance in pregnancy have lagged, however the establishment of this natural state is significant. Reproduction and energy balance are tightly controlled and backed up by redundant mechanisms that are critical for the survival of our species. It will be the goal of the next decade to shed new light on these complex and essential pathways. PMID:25118207

  7. Transmembrane proteins UNC-40/DCC, PTP-3/LAR, and MIG-21 control anterior-posterior neuroblast migration with left-right functional asymmetry in Caenorhabditis elegans.

    PubMed

    Sundararajan, Lakshmi; Lundquist, Erik A

    2012-12-01

    Migration of neurons and neural crest cells is of central importance to the development of nervous systems. In Caenorhabditis elegans, the QL neuroblast on the left migrates posteriorly, and QR on the right migrates anteriorly, despite similar lineages and birth positions with regard to the left-right axis. Initial migration is independent of a Wnt signal that controls later anterior-posterior Q descendant migration. Previous studies showed that the transmembrane proteins UNC-40/DCC and MIG-21, a novel thrombospondin type I repeat containing protein, act redundantly in left-side QL posterior migration. Here we show that the LAR receptor protein tyrosine phosphatase PTP-3 acts with MIG-21 in parallel to UNC-40 in QL posterior migration. We also show that in right-side QR, the UNC-40 and PTP-3/MIG-21 pathways mutually inhibit each other's role in posterior migration, allowing anterior QR migration. Finally, we present evidence that these proteins act autonomously in the Q neuroblasts. These studies indicate an inherent left-right asymmetry in the Q neuroblasts with regard to UNC-40, PTP-3, and MIG-21 function that results in posterior vs. anterior migration.

  8. Examining impairment of adaptive compensation for stabilizing motor repetitions in stroke survivors.

    PubMed

    Kim, Yushin; Koh, Kyung; Yoon, BumChul; Kim, Woo-Sub; Shin, Joon-Ho; Park, Hyung-Soon; Shim, Jae Kun

    2017-12-01

    The hand, one of the most versatile but mechanically redundant parts of the human body, suffers more and longer than other body parts after stroke. One of the rehabilitation paradigms, task-oriented rehabilitation, encourages motor repeatability, the ability to produce similar motor performance over repetitions through compensatory strategies while taking advantage of the motor system's redundancy. The previous studies showed that stroke survivors inconsistently performed a given motor task with limited motor solutions. We hypothesized that stroke survivors would exhibit deficits in motor repeatability and adaptive compensation compared to healthy controls in during repetitive force-pulse (RFP) production tasks using multiple fingers. Seventeen hemiparetic stroke survivors and seven healthy controls were asked to repeatedly press force sensors as fast as possible using the four fingers of each hand. The hierarchical variability decomposition model was employed to compute motor repeatability and adaptive compensation across finger-force impulses, respectively. Stroke survivors showed decreased repeatability and adaptive compensation of force impulses between individual fingers as compared to the control (p < 0.05). The stroke survivors also showed decreased pulse frequency and greater peak-to-peak time variance than the control (p < 0.05). Force-related variables, such as mean peak force and peak force interval variability, demonstrated no significant difference between groups. Our findings indicate that stroke-induced brain injury negatively affects their ability to exploit their redundant or abundant motor system in an RFP task.

  9. Individual differences in working memory capacity and workload capacity.

    PubMed

    Yu, Ju-Chi; Chang, Ting-Yun; Yang, Cheng-Ta

    2014-01-01

    We investigated the relationship between working memory capacity (WMC) and workload capacity (WLC). Each participant performed an operation span (OSPAN) task to measure his/her WMC and three redundant-target detection tasks to measure his/her WLC. WLC was computed non-parametrically (Experiments 1 and 2) and parametrically (Experiment 2). Both levels of analyses showed that participants high in WMC had larger WLC than those low in WMC only when redundant information came from visual and auditory modalities, suggesting that high-WMC participants had superior processing capacity in dealing with redundant visual and auditory information. This difference was eliminated when multiple processes required processing for only a single working memory subsystem in a color-shape detection task and a double-dot detection task. These results highlighted the role of executive control in integrating and binding information from the two working memory subsystems for perceptual decision making.

  10. Factors which Limit the Value of Additional Redundancy in Human Rated Launch Vehicle Systems

    NASA Technical Reports Server (NTRS)

    Anderson, Joel M.; Stott, James E.; Ring, Robert W.; Hatfield, Spencer; Kaltz, Gregory M.

    2008-01-01

    The National Aeronautics and Space Administration (NASA) has embarked on an ambitious program to return humans to the moon and beyond. As NASA moves forward in the development and design of new launch vehicles for future space exploration, it must fully consider the implications that rule-based requirements of redundancy or fault tolerance have on system reliability/risk. These considerations include common cause failure, increased system complexity, combined serial and parallel configurations, and the impact of design features implemented to control premature activation. These factors and others must be considered in trade studies to support design decisions that balance safety, reliability, performance and system complexity to achieve a relatively simple, operable system that provides the safest and most reliable system within the specified performance requirements. This paper describes conditions under which additional functional redundancy can impede improved system reliability. Examples from current NASA programs including the Ares I Upper Stage will be shown.

  11. Redundant drive current imbalance problem of the Automatic Radiator Inspection Device (ARID)

    NASA Technical Reports Server (NTRS)

    Latino, Carl D.

    1992-01-01

    The Automatic Radiator Inspection Device (ARID) is a 4 Degree of Freedom (DOF) robot with redundant drive motors at each joint. The device is intended to automate the labor intensive task of space shuttle radiator inspection. For safety and redundancy, each joint is driven by two independent motor systems. Motors driving the same joint, however, draw vastly different currents. The concern was that the robot joints could be subjected to undue stress. It was the objective of this summer's project to determine the cause of this current imbalance. In addition it was to determine, in a quantitative manner, what was the cause, how serious the problem was in terms of damage or undue wear to the robot and find solutions if possible. It was concluded that most problems could be resolved with a better motor control design. This document discusses problems encountered and possible solutions.

  12. Information and redundancy: key concepts in understanding the genetic control of health and intelligence.

    PubMed

    Morris, J A

    1999-08-01

    A model is proposed in which information from the environment is analysed by complex biological decision-making systems which are highly redundant. A correct response is intelligent behaviour which preserves health; incorrect responses lead to disease. Mutations in genes which code for the redundant systems will accumulate in the genome and impair decision-making. The number of mutant genes will depend upon a balance between the new mutation rate per generation and systems of elimination based on synergistic interaction in redundant systems. This leads to a polygenic pattern of inheritance for intelligence and the common diseases. The model also gives a simple explanation for some of the hitherto puzzling aspects of work on the genetic basis of intelligence including the recorded rise in IQ this century. There is a prediction that health, intelligence and socio-economic position will be correlated generating a health differential in the social hierarchy. Furthermore, highly competitive societies will place those least able to cope in the harshest environment and this will impair health overall. The model points to a need for population monitoring of somatic mutation in order to preserve the health and intelligence of future generations.

  13. Sibling rivalry: related bacterial small RNAs and their redundant and non-redundant roles

    PubMed Central

    Caswell, Clayton C.; Oglesby-Sherrouse, Amanda G.; Murphy, Erin R.

    2014-01-01

    Small RNA molecules (sRNAs) are now recognized as key regulators controlling bacterial gene expression, as sRNAs provide a quick and efficient means of positively or negatively altering the expression of specific genes. To date, numerous sRNAs have been identified and characterized in a myriad of bacterial species, but more recently, a theme in bacterial sRNAs has emerged: the presence of more than one highly related sRNAs produced by a given bacterium, here termed sibling sRNAs. Sibling sRNAs are those that are highly similar at the nucleotide level, and while it might be expected that sibling sRNAs exert identical regulatory functions on the expression of target genes based on their high degree of relatedness, emerging evidence is demonstrating that this is not always the case. Indeed, there are several examples of bacterial sibling sRNAs with non-redundant regulatory functions, but there are also instances of apparent regulatory redundancy between sibling sRNAs. This review provides a comprehensive overview of the current knowledge of bacterial sibling sRNAs, and also discusses important questions about the significance and evolutionary implications of this emerging class of regulators. PMID:25389522

  14. Sibling rivalry: related bacterial small RNAs and their redundant and non-redundant roles.

    PubMed

    Caswell, Clayton C; Oglesby-Sherrouse, Amanda G; Murphy, Erin R

    2014-01-01

    Small RNA molecules (sRNAs) are now recognized as key regulators controlling bacterial gene expression, as sRNAs provide a quick and efficient means of positively or negatively altering the expression of specific genes. To date, numerous sRNAs have been identified and characterized in a myriad of bacterial species, but more recently, a theme in bacterial sRNAs has emerged: the presence of more than one highly related sRNAs produced by a given bacterium, here termed sibling sRNAs. Sibling sRNAs are those that are highly similar at the nucleotide level, and while it might be expected that sibling sRNAs exert identical regulatory functions on the expression of target genes based on their high degree of relatedness, emerging evidence is demonstrating that this is not always the case. Indeed, there are several examples of bacterial sibling sRNAs with non-redundant regulatory functions, but there are also instances of apparent regulatory redundancy between sibling sRNAs. This review provides a comprehensive overview of the current knowledge of bacterial sibling sRNAs, and also discusses important questions about the significance and evolutionary implications of this emerging class of regulators.

  15. Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair.

    PubMed

    Marsischky, G T; Filosi, N; Kane, M F; Kolodner, R

    1996-02-15

    Saccharomyces cerevisiae encodes six genes, MSH1-6, which encode proteins related to the bacterial MutS protein. In this study the role of MSH2, MSH3, and MSH6 in mismatch repair has been examined by measuring the rate of accumulating mutations and mutation spectrum in strains containing different combinations of msh2, msh3, and msh6 mutations and by studying the physical interaction between the MSH2 protein and the MSH3 and MSH6 proteins. The results indicate that S. cerevisiae has two pathways of MSH2-dependent mismatch repair: one that recognized single-base mispairs and requires MSH2 and MSH6, and a second that recognizes insertion/deletion mispairs and requires a combination of either MSH2 and MSH6 or MSH2 and MSH3. The redundancy of MSH3 and MSH6 explains the greater prevalence of hmsh2 mutations in HNPCC families and suggests how the role of hmsh3 and hmsh6 mutations in cancer susceptibility could be analyzed.

  16. Neural Sequence Generation Using Spatiotemporal Patterns of Inhibition.

    PubMed

    Cannon, Jonathan; Kopell, Nancy; Gardner, Timothy; Markowitz, Jeffrey

    2015-11-01

    Stereotyped sequences of neural activity are thought to underlie reproducible behaviors and cognitive processes ranging from memory recall to arm movement. One of the most prominent theoretical models of neural sequence generation is the synfire chain, in which pulses of synchronized spiking activity propagate robustly along a chain of cells connected by highly redundant feedforward excitation. But recent experimental observations in the avian song production pathway during song generation have shown excitatory activity interacting strongly with the firing patterns of inhibitory neurons, suggesting a process of sequence generation more complex than feedforward excitation. Here we propose a model of sequence generation inspired by these observations in which a pulse travels along a spatially recurrent excitatory chain, passing repeatedly through zones of local feedback inhibition. In this model, synchrony and robust timing are maintained not through redundant excitatory connections, but rather through the interaction between the pulse and the spatiotemporal pattern of inhibition that it creates as it circulates the network. These results suggest that spatially and temporally structured inhibition may play a key role in sequence generation.

  17. Hearing in noisy environments: noise invariance and contrast gain control

    PubMed Central

    Willmore, Ben D B; Cooke, James E; King, Andrew J

    2014-01-01

    Contrast gain control has recently been identified as a fundamental property of the auditory system. Electrophysiological recordings in ferrets have shown that neurons continuously adjust their gain (their sensitivity to change in sound level) in response to the contrast of sounds that are heard. At the level of the auditory cortex, these gain changes partly compensate for changes in sound contrast. This means that sounds which are structurally similar, but have different contrasts, have similar neuronal representations in the auditory cortex. As a result, the cortical representation is relatively invariant to stimulus contrast and robust to the presence of noise in the stimulus. In the inferior colliculus (an important subcortical auditory structure), gain changes are less reliably compensatory, suggesting that contrast- and noise-invariant representations are constructed gradually as one ascends the auditory pathway. In addition to noise invariance, contrast gain control provides a variety of computational advantages over static neuronal representations; it makes efficient use of neuronal dynamic range, may contribute to redundancy-reducing, sparse codes for sound and allows for simpler decoding of population responses. The circuits underlying auditory contrast gain control are still under investigation. As in the visual system, these circuits may be modulated by factors other than stimulus contrast, forming a potential neural substrate for mediating the effects of attention as well as interactions between the senses. PMID:24907308

  18. The PHD-containing protein EARLY BOLTING IN SHORT DAYS regulates seed dormancy in Arabidopsis.

    PubMed

    Narro-Diego, Laura; López-González, Leticia; Jarillo, Jose A; Piñeiro, Manuel

    2017-10-01

    The Arabidopsis protein EARLY BOLTING IN SHORT DAYS (EBS), a plant-specific transcriptional regulator, is involved in the control of flowering time by repressing the floral integrator FT. The EBS protein binds the H3K4me3 histone mark and interacts with histone deacetylases to modulate gene expression. Here, we show that EBS also participates in the regulation of seed dormancy. ebs mutations cause a reduction in seed dormancy, and the concurrent loss of function of the EBS homologue SHORT LIFE (SHL) enhances this dormancy alteration. Transcriptomic analyses in ebs mutant seeds uncovered the misregulation of several regulators of seed dormancy including the MADS box gene AGAMOUS-LIKE67 (AGL67). AGL67 interacts genetically with EBS in seed dormancy regulation, indicating that both loci act in the same pathway. Interestingly, EBS functions independently of the master regulator gene of dormancy DELAY OF GERMINATION 1 (DOG1) and other genes encoding chromatin remodelling factors involved in the control of seed dormancy. Altogether, these data show that EBS is a central repressor of germination during seed dormancy and that SHL acts redundantly with EBS in the control of this developmental process. Our observations suggest that a tightly regulated crosstalk among histone modifications is necessary for a proper control of seed dormancy. © 2017 John Wiley & Sons Ltd.

  19. Universal mechanisms of sound production and control in birds and mammals

    PubMed Central

    Elemans, C.P.H; Rasmussen, J.H.; Herbst, C.T.; Düring, D.N.; Zollinger, S.A.; Brumm, H.; Srivastava, K.; Svane, N.; Ding, M.; Larsen, O.N.; Sober, S.J.; Švec, J.G.

    2015-01-01

    As animals vocalize, their vocal organ transforms motor commands into vocalizations for social communication. In birds, the physical mechanisms by which vocalizations are produced and controlled remain unresolved because of the extreme difficulty in obtaining in vivo measurements. Here, we introduce an ex vivo preparation of the avian vocal organ that allows simultaneous high-speed imaging, muscle stimulation and kinematic and acoustic analyses to reveal the mechanisms of vocal production in birds across a wide range of taxa. Remarkably, we show that all species tested employ the myoelastic-aerodynamic (MEAD) mechanism, the same mechanism used to produce human speech. Furthermore, we show substantial redundancy in the control of key vocal parameters ex vivo, suggesting that in vivo vocalizations may also not be specified by unique motor commands. We propose that such motor redundancy can aid vocal learning and is common to MEAD sound production across birds and mammals, including humans. PMID:26612008

  20. Universal mechanisms of sound production and control in birds and mammals.

    PubMed

    Elemans, C P H; Rasmussen, J H; Herbst, C T; Düring, D N; Zollinger, S A; Brumm, H; Srivastava, K; Svane, N; Ding, M; Larsen, O N; Sober, S J; Švec, J G

    2015-11-27

    As animals vocalize, their vocal organ transforms motor commands into vocalizations for social communication. In birds, the physical mechanisms by which vocalizations are produced and controlled remain unresolved because of the extreme difficulty in obtaining in vivo measurements. Here, we introduce an ex vivo preparation of the avian vocal organ that allows simultaneous high-speed imaging, muscle stimulation and kinematic and acoustic analyses to reveal the mechanisms of vocal production in birds across a wide range of taxa. Remarkably, we show that all species tested employ the myoelastic-aerodynamic (MEAD) mechanism, the same mechanism used to produce human speech. Furthermore, we show substantial redundancy in the control of key vocal parameters ex vivo, suggesting that in vivo vocalizations may also not be specified by unique motor commands. We propose that such motor redundancy can aid vocal learning and is common to MEAD sound production across birds and mammals, including humans.

  1. Control of the seven-degree-of-freedom upper limb exoskeleton for an improved human-robot interface

    NASA Astrophysics Data System (ADS)

    Kim, Hyunchul; Kim, Jungsuk

    2017-04-01

    This study analyzes a practical scheme for controlling an exoskeleton robot with seven degrees of freedom (DOFs) that supports natural movements of the human arm. A redundant upper limb exoskeleton robot with seven DOFs is mechanically coupled to the human body such that it becomes a natural extension of the body. If the exoskeleton robot follows the movement of the human body synchronously, the energy exchange between the human and the robot will be reduced significantly. In order to achieve this, the redundancy of the human arm, which is represented by the swivel angle, should be resolved using appropriate constraints and applied to the robot. In a redundant 7-DOF upper limb exoskeleton, the pseudoinverse of the Jacobian with secondary objective functions is widely used to resolve the redundancy that defines the desired joint angles. A secondary objective function requires the desired joint angles for the movement of the human arm, and the angles are estimated by maximizing the projection of the longest principle axis of the manipulability ellipsoid for the human arm onto the virtual destination toward the head region. Then, they are fed into the muscle model with a relative damping to achieve more realistic robot-arm movements. Various natural arm movements are recorded using a motion capture system, and the actual swivel-angle is compared to that estimated using the proposed swivel angle estimation algorithm. The results indicate that the proposed algorithm provides a precise reference for estimating the desired joint angle with an error less than 5°.

  2. Concurrent information affects response inhibition processes via the modulation of theta oscillations in cognitive control networks.

    PubMed

    Chmielewski, Witold X; Mückschel, Moritz; Dippel, Gabriel; Beste, Christian

    2016-11-01

    Inhibiting responses is a challenge, where the outcome (partly) depends on the situational context. In everyday situations, response inhibition performance might be altered when irrelevant input is presented simultaneously with the information relevant for response inhibition. More specifically, irrelevant concurrent information may either brace or interfere with response-relevant information, depending on whether these inputs are redundant or conflicting. The aim of this study is to investigate neurophysiological mechanisms and the network underlying such modulations using EEG beamforming as method. The results show that in comparison to a baseline condition without concurrent information, response inhibition performance can be aggravated or facilitated by manipulating the extent of conflict via concurrent input. This depends on whether the requirement for cognitive control is high, as in conflicting trials, or whether it is low, as in redundant trials. In line with this, the total theta frequency power decreases in a right hemispheric orbitofrontal response inhibition network including the SFG, MFG, and SMA, when concurrent redundant information facilitates response inhibition processes. Vice versa, theta activity in a left-hemispheric response inhibition network (i.e., SFG, MFG, and IFG) increases, when conflicting concurrent information compromises response inhibition processes. We conclude that concurrent information bi-directionally shifts response inhibition performance and modulates the network architecture underlying theta oscillations which are signaling different levels of the need for cognitive control.

  3. RNA-Seq transcriptomic analysis of the Morus alba L. leaves exposed to high-level UVB with or without dark treatment.

    PubMed

    Guan, Qijie; Yu, Jiaojiao; Zhu, Wei; Yang, Bingxian; Li, Yaohan; Zhang, Lin; Tian, Jingkui

    2018-03-01

    Ultraviolet-B (UVB) irradiation induces oxidative stress in plant cells due to the generation of excessive reactive oxygen species. Morus alba L. (M. abla) is an important medicinal plant used for the treatment of human diseases. Also, its leaves are widely used as food for silkworms. In our previous research, we found that a high level of UVB irradiation with dark incubation led to the accumulation of secondary metabolites in M. abla leaf. The aim of the present study was to describe and compare M. alba leaf transcriptomics with different treatments (control, UVB, UVB+dark). Leaf transcripts from M. alba were sequenced using an Illumina Hiseq 2000 system, which produced 14.27Gb of data including 153,204,462 paired-end reads among the three libraries. We de novo assembled 133,002 transcripts with an average length of 1270bp and filtered 69,728 non-redundant unigenes. A similarity search was performed against the non-redundant National Center of Biotechnology Information (NCBI) protein database, which returned 41.08% hits. Among the 20,040 unigenes annotated in UniProtKB/SwissProt database, 16,683 unigenes were assigned 102,232 gene ontology terms and 6667 unigenes were identified in 287 known metabolic pathways. Results of differential gene expression analysis together with real-time quantitative PCR tests indicated that UVB irradiation with dark incubation enhanced the flavonoid biosynthesis in M. alba leaf. Our findings provided a valuable proof for a better understanding of the metabolic mechanism under abiotic stresses in M. alba leaf. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. The Birth and Death of Redundancy in Decoherence and Quantum Darwinism

    NASA Astrophysics Data System (ADS)

    Riedel, Charles; Zurek, Wojciech; Zwolak, Michael

    2012-02-01

    Understanding the quantum-classical transition and the identification of a preferred classical domain through quantum Darwinism is based on recognizing high-redundancy states as both ubiquitous and exceptional. They are produced ubiquitously during decoherence, as has been demonstrated by the recent identification of very general conditions under which high-redundancy states develop. They are exceptional in that high-redundancy states occupy a very narrow corner of the global Hilbert space; states selected at random are overwelming likely to exhibit zero redundancy. In this letter, we examine the conditions and time scales for the transition from high-redundancy states to zero-redundancy states in many-body dynamics. We identify sufficient condition for the development of redundancy from product states and show that the destruction of redundancy can be accomplished even with highly constrained interactions.

  5. Connected Dominating Set Based Topology Control in Wireless Sensor Networks

    ERIC Educational Resources Information Center

    He, Jing

    2012-01-01

    Wireless Sensor Networks (WSNs) are now widely used for monitoring and controlling of systems where human intervention is not desirable or possible. Connected Dominating Sets (CDSs) based topology control in WSNs is one kind of hierarchical method to ensure sufficient coverage while reducing redundant connections in a relatively crowded network.…

  6. The Effects of Race Conditions When Implementing Single-Source Redundant Clock Trees in Triple Modular Redundant Synchronous Architectures

    NASA Technical Reports Server (NTRS)

    Berg, Melanie D.; Kim, Hak S.; Phan, Anthony M.; Seidleck, Christina M.; Label, Kenneth A.; Pellish, Jonathan A.; Campola, Michael J.

    2016-01-01

    We present the challenges that arise when using redundant clock domains due to their time-skew. Radiation data show that a singular clock domain provides an improved triple modular redundant (TMR) scheme over redundant clocks.

  7. SOCS-1 localizes to the microtubule organizing complex-associated 20S proteasome.

    PubMed

    Vuong, Bao Q; Arenzana, Teresita L; Showalter, Brian M; Losman, Julie; Chen, X Peter; Mostecki, Justin; Banks, Alexander S; Limnander, Andre; Fernandez, Neil; Rothman, Paul B

    2004-10-01

    The regulation of cytokine signaling is critical for controlling cellular proliferation and activation during an immune response. SOCS-1 is a potent inhibitor of Jak kinase activity and of signaling initiated by several cytokines. SOCS-1 protein levels are tightly regulated, and recent data suggest that SOCS-1 may regulate the protein levels of some signaling proteins by the ubiquitin proteasome pathway; however, the cellular mechanism by which SOCS-1 directs proteins for degradation is unknown. In this report, SOCS-1 is found to colocalize and biochemically copurify with the microtubule organizing complex (MTOC) and its associated 20S proteasome. The SOCS-1 SH2 domain is required for the localization of SOCS-1 to the MTOC. Overexpression of SOCS-1 targets Jak1 in an SH2-dependent manner to a perinuclear distribution resembling the MTOC-associated 20S proteasome. Analysis of MTOCs fractionated from SOCS-1-deficient cells demonstrates that SOCS-1 may function redundantly to regulate the localization of Jak1 to the MTOC. Nocodazole inhibits the protein turnover of SOCS-1, demonstrating that the minus-end transport of SOCS-1 to the MTOC-associated 20S proteasome is required to regulate SOCS-1 protein levels. These data link SOCS-1 directly with the proteasome pathway and suggest another function for the SH2 domain of SOCS-1 in the regulation of Jak/STAT signaling.

  8. Stochastic Effects in Computational Biology of Space Radiation Cancer Risk

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.; Pluth, Janis; Harper, Jane; O'Neill, Peter

    2007-01-01

    Estimating risk from space radiation poses important questions on the radiobiology of protons and heavy ions. We are considering systems biology models to study radiation induced repair foci (RIRF) at low doses, in which less than one-track on average transverses the cell, and the subsequent DNA damage processing and signal transduction events. Computational approaches for describing protein regulatory networks coupled to DNA and oxidative damage sites include systems of differential equations, stochastic equations, and Monte-Carlo simulations. We review recent developments in the mathematical description of protein regulatory networks and possible approaches to radiation effects simulation. These include robustness, which states that regulatory networks maintain their functions against external and internal perturbations due to compensating properties of redundancy and molecular feedback controls, and modularity, which leads to general theorems for considering molecules that interact through a regulatory mechanism without exchange of matter leading to a block diagonal reduction of the connecting pathways. Identifying rate-limiting steps, robustness, and modularity in pathways perturbed by radiation damage are shown to be valid techniques for reducing large molecular systems to realistic computer simulations. Other techniques studied are the use of steady-state analysis, and the introduction of composite molecules or rate-constants to represent small collections of reactants. Applications of these techniques to describe spatial and temporal distributions of RIRF and cell populations following low dose irradiation are described.

  9. Fuzzy logic control of telerobot manipulators

    NASA Technical Reports Server (NTRS)

    Franke, Ernest A.; Nedungadi, Ashok

    1992-01-01

    Telerobot systems for advanced applications will require manipulators with redundant 'degrees of freedom' (DOF) that are capable of adapting manipulator configurations to avoid obstacles while achieving the user specified goal. Conventional methods for control of manipulators (based on solution of the inverse kinematics) cannot be easily extended to these situations. Fuzzy logic control offers a possible solution to these needs. A current research program at SRI developed a fuzzy logic controller for a redundant, 4 DOF, planar manipulator. The manipulator end point trajectory can be specified by either a computer program (robot mode) or by manual input (teleoperator). The approach used expresses end-point error and the location of manipulator joints as fuzzy variables. Joint motions are determined by a fuzzy rule set without requiring solution of the inverse kinematics. Additional rules for sensor data, obstacle avoidance and preferred manipulator configuration, e.g., 'righty' or 'lefty', are easily accommodated. The procedure used to generate the fuzzy rules can be extended to higher DOF systems.

  10. Utilization of kinematical redundancy of a rehabilitation robot to produce compliant motions under limitation on actuator performance.

    PubMed

    Goto, Takaaki; Dobashi, Hiroki; Yoshikawa, Tsuneo; Loureiro, Rui C V; Harwin, William S; Miyamura, Yuga; Nagai, Kiyoshi

    2017-07-01

    This paper addresses the mechanical structure and control method of a redundant drive robot (RDR) to produce compliant motions, and show how the design parameters of the RDR can effect the produced motions and the mechanical and performance limitations of the actuators of the RDR. The structure and control method of the RDR can have been proper to produce compliant motions, but the effect of the design parameters of the RDR to the mechanical and performance limitations have not been clear. Therefore, the feasibility of producing compliant motions in the case of the prototype of the RDR is confirmed by conducting simulations and experiments, and then the design parameters of the RDR to the mechanical and performance limitations are verified by conducting simulations.

  11. Burkholderia xenovorans LB400 harbors a multi-replicon, 9.73-Mbp genome shaped for versatility

    PubMed Central

    Chain, Patrick S. G.; Denef, Vincent J.; Konstantinidis, Konstantinos T.; Vergez, Lisa M.; Agulló, Loreine; Reyes, Valeria Latorre; Hauser, Loren; Córdova, Macarena; Gómez, Luis; González, Myriam; Land, Miriam; Lao, Victoria; Larimer, Frank; LiPuma, John J.; Mahenthiralingam, Eshwar; Malfatti, Stephanie A.; Marx, Christopher J.; Parnell, J. Jacob; Ramette, Alban; Richardson, Paul; Seeger, Michael; Smith, Daryl; Spilker, Theodore; Sul, Woo Jun; Tsoi, Tamara V.; Ulrich, Luke E.; Zhulin, Igor B.; Tiedje, James M.

    2006-01-01

    Burkholderia xenovorans LB400 (LB400), a well studied, effective polychlorinated biphenyl-degrader, has one of the two largest known bacterial genomes and is the first nonpathogenic Burkholderia isolate sequenced. From an evolutionary perspective, we find significant differences in functional specialization between the three replicons of LB400, as well as a more relaxed selective pressure for genes located on the two smaller vs. the largest replicon. High genomic plasticity, diversity, and specialization within the Burkholderia genus are exemplified by the conservation of only 44% of the genes between LB400 and Burkholderia cepacia complex strain 383. Even among four B. xenovorans strains, genome size varies from 7.4 to 9.73 Mbp. The latter is largely explained by our findings that >20% of the LB400 sequence was recently acquired by means of lateral gene transfer. Although a range of genetic factors associated with in vivo survival and intercellular interactions are present, these genetic factors are likely related to niche breadth rather than determinants of pathogenicity. The presence of at least eleven “central aromatic” and twenty “peripheral aromatic” pathways in LB400, among the highest in any sequenced bacterial genome, supports this hypothesis. Finally, in addition to the experimentally observed redundancy in benzoate degradation and formaldehyde oxidation pathways, the fact that 17.6% of proteins have a better LB400 paralog than an ortholog in a different genome highlights the importance of gene duplication and repeated acquirement, which, coupled with their divergence, raises questions regarding the role of paralogs and potential functional redundancies in large-genome microbes. PMID:17030797

  12. Exceptional reduction of the plastid genome of saguaro cactus (Carnegiea gigantea): Loss of the ndh gene suite and inverted repeat.

    PubMed

    Sanderson, Michael J; Copetti, Dario; Búrquez, Alberto; Bustamante, Enriquena; Charboneau, Joseph L M; Eguiarte, Luis E; Kumar, Sudhir; Lee, Hyun Oh; Lee, Junki; McMahon, Michelle; Steele, Kelly; Wing, Rod; Yang, Tae-Jin; Zwickl, Derrick; Wojciechowski, Martin F

    2015-07-01

    • Land-plant plastid genomes have only rarely undergone significant changes in gene content and order. Thus, discovery of additional examples adds power to tests for causes of such genome-scale structural changes.• Using next-generation sequence data, we assembled the plastid genome of saguaro cactus and probed the nuclear genome for transferred plastid genes and functionally related nuclear genes. We combined these results with available data across Cactaceae and seed plants more broadly to infer the history of gene loss and to assess the strength of phylogenetic association between gene loss and loss of the inverted repeat (IR).• The saguaro plastid genome is the smallest known for an obligately photosynthetic angiosperm (∼113 kb), having lost the IR and plastid ndh genes. This loss supports a statistically strong association across seed plants between the loss of ndh genes and the loss of the IR. Many nonplastid copies of plastid ndh genes were found in the nuclear genome, but none had intact reading frames; nor did three related nuclear-encoded subunits. However, nuclear pgr5, which functions in a partially redundant pathway, was intact.• The existence of an alternative pathway redundant with the function of the plastid NADH dehydrogenase-like complex (NDH) complex may permit loss of the plastid ndh gene suite in photoautotrophs like saguaro. Loss of these genes may be a recurring mechanism for overall plastid genome size reduction, especially in combination with loss of the IR. © 2015 Botanical Society of America, Inc.

  13. Burkholderia xernovorans LB400 harbors a multi-replicon, 9.73-Mbp genome shaped for versatility

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

    Chain, Patrick S. G.; Denef, Vincent; Konstantinidis, Konstantinos T

    2006-01-01

    Burkholderia xenovorans LB400 (LB400), a well studied, effective polychlorinated biphenyl-degrader, has one of the two largest known bacterial genomes and is the first nonpathogenic Burkholderia isolate sequenced. From an evolutionary perspective, we find significant differences in functional specialization between the three replicons of LB400, as well as a more relaxed selective pressure for genes located on the two smaller vs. the largest replicon. High genomic plasticity, diversity, and specialization within the Burkholderia genus are exemplified by the conservation of only 44% of the genes between LB400 and Burkholderia cepacia complex strain 383. Even among four B. xenovorans strains, genome sizemore » varies from 7.4 to 9.73 Mbp. The latter is largely explained by our findings that >20% of the LB400 sequence was recently acquired by means of lateral gene transfer. Although a range of genetic factors associated with in vivo survival and intercellular interactions are present, these genetic factors are likely related to niche breadth rather than determinants of pathogenicity. The presence of at least eleven 'central aromatic' and twenty 'peripheral aromatic' pathways in LB400, among the highest in any sequenced bacterial genome, supports this hypothesis. Finally, in addition to the experimentally observed redundancy in benzoate degradation and formaldehyde oxidation pathways, the fact that 17.6% of proteins have a better LB400 paralog than an ortholog in a different genome highlights the importance of gene duplication and repeated acquirement, which, coupled with their divergence, raises questions regarding the role of paralogs and potential functional redundancies in large-genome microbes.« less

  14. Management of pulmonary arterial hypertension with a focus on combination therapies.

    PubMed

    Benza, Raymond L; Park, Myung H; Keogh, Anne; Girgis, Reda E

    2007-05-01

    Pulmonary arterial hypertension (PAH) is a rare but frequently fatal condition marked by vasoconstriction and vascular remodeling within small pulmonary arteries. The pathobiology of PAH involves imbalances in a multitude of endogenous mediators, which promote aberrant cellular growth, vasoconstriction and hemostasis within the pulmonary vascular tree. The mechanisms promoting these pathologic effects are complex. This complexity is highlighted by the many overlapping secondary messenger systems through which these mediators work. In light of this natural redundancy, it is not surprising that many of the drugs used to treat PAH, which have shown short-term efficacy, fall "short of the mark" in reversing or halting the progression of this disease in the long run. This very redundancy in pathways makes the case for the use of combination of drugs with differing mechanisms of action to treat PAH. Similar to what is now accepted as the standard of care for the treatment of cancer and left ventricular dysfunction, combination therapy has the greatest promise for inducing the most complete vascular remodeling of the pulmonary vasculature by "shutting down" as many of these pathologic pathways as possible. Combination therapies involving existing therapies or new agents with improved pharmacokinetic and/or pharmacodynamic properties represent an emerging clinical paradigm for patients with sub-optimally managed disease. As emerging data in this field of therapy comes to fruition, further reductions in the morbidity and mortality associated with PAH will manifest. The goal of this report is to review the philosophy of combination therapy and present the available data in this area of study.

  15. Contrasting dynamic responses in vivo of the Bcl-xL and Bim erythropoietic survival pathways

    PubMed Central

    Koulnis, Miroslav; Porpiglia, Ermelinda; Porpiglia, P. Alberto; Liu, Ying; Hallstrom, Kelly; Hidalgo, Daniel

    2012-01-01

    Survival signaling by the erythropoietin (Epo) receptor (EpoR) is essential for erythropoiesis and for its acceleration in hypoxic stress. Several apparently redundant EpoR survival pathways were identified in vitro, raising the possibility of their functional specialization in vivo. Here we used mouse models of acute and chronic stress, including a hypoxic environment and β-thalassemia, to identify two markedly different response dynamics for two erythroblast survival pathways in vivo. Induction of the antiapoptotic protein Bcl-xL is rapid but transient, while suppression of the proapoptotic protein Bim is slower but persistent. Similar to sensory adaptation, however, the Bcl-xL pathway “resets,” allowing it to respond afresh to acute stress superimposed on a chronic stress stimulus. Using “knock-in” mouse models expressing mutant EpoRs, we found that adaptation in the Bcl-xL response occurs because of adaptation of its upstream regulator Stat5, both requiring the EpoR distal cytoplasmic domain. We conclude that survival pathways show previously unsuspected functional specialization for the acute and chronic phases of the stress response. Bcl-xL induction provides a “stop-gap” in acute stress, until slower but permanent pathways are activated. Furthermore, pathologic elevation of Bcl-xL may be the result of impaired adaptation, with implications for myeloproliferative disease mechanisms. PMID:22086418

  16. Network analysis of genomic alteration profiles reveals co-altered functional modules and driver genes for glioblastoma.

    PubMed

    Gu, Yunyan; Wang, Hongwei; Qin, Yao; Zhang, Yujing; Zhao, Wenyuan; Qi, Lishuang; Zhang, Yuannv; Wang, Chenguang; Guo, Zheng

    2013-03-01

    The heterogeneity of genetic alterations in human cancer genomes presents a major challenge to advancing our understanding of cancer mechanisms and identifying cancer driver genes. To tackle this heterogeneity problem, many approaches have been proposed to investigate genetic alterations and predict driver genes at the individual pathway level. However, most of these approaches ignore the correlation of alteration events between pathways and miss many genes with rare alterations collectively contributing to carcinogenesis. Here, we devise a network-based approach to capture the cooperative functional modules hidden in genome-wide somatic mutation and copy number alteration profiles of glioblastoma (GBM) from The Cancer Genome Atlas (TCGA), where a module is a set of altered genes with dense interactions in the protein interaction network. We identify 7 pairs of significantly co-altered modules that involve the main pathways known to be altered in GBM (TP53, RB and RTK signaling pathways) and highlight the striking co-occurring alterations among these GBM pathways. By taking into account the non-random correlation of gene alterations, the property of co-alteration could distinguish oncogenic modules that contain driver genes involved in the progression of GBM. The collaboration among cancer pathways suggests that the redundant models and aggravating models could shed new light on the potential mechanisms during carcinogenesis and provide new indications for the design of cancer therapeutic strategies.

  17. Prediction and analysis of essential genes using the enrichments of gene ontology and KEGG pathways.

    PubMed

    Chen, Lei; Zhang, Yu-Hang; Wang, ShaoPeng; Zhang, YunHua; Huang, Tao; Cai, Yu-Dong

    2017-01-01

    Identifying essential genes in a given organism is important for research on their fundamental roles in organism survival. Furthermore, if possible, uncovering the links between core functions or pathways with these essential genes will further help us obtain deep insight into the key roles of these genes. In this study, we investigated the essential and non-essential genes reported in a previous study and extracted gene ontology (GO) terms and biological pathways that are important for the determination of essential genes. Through the enrichment theory of GO and KEGG pathways, we encoded each essential/non-essential gene into a vector in which each component represented the relationship between the gene and one GO term or KEGG pathway. To analyze these relationships, the maximum relevance minimum redundancy (mRMR) was adopted. Then, the incremental feature selection (IFS) and support vector machine (SVM) were employed to extract important GO terms and KEGG pathways. A prediction model was built simultaneously using the extracted GO terms and KEGG pathways, which yielded nearly perfect performance, with a Matthews correlation coefficient of 0.951, for distinguishing essential and non-essential genes. To fully investigate the key factors influencing the fundamental roles of essential genes, the 21 most important GO terms and three KEGG pathways were analyzed in detail. In addition, several genes was provided in this study, which were predicted to be essential genes by our prediction model. We suggest that this study provides more functional and pathway information on the essential genes and provides a new way to investigate related problems.

  18. Robust inverse kinematics using damped least squares with dynamic weighting

    NASA Technical Reports Server (NTRS)

    Schinstock, D. E.; Faddis, T. N.; Greenway, R. B.

    1994-01-01

    This paper presents a general method for calculating the inverse kinematics with singularity and joint limit robustness for both redundant and non-redundant serial-link manipulators. Damped least squares inverse of the Jacobian is used with dynamic weighting matrices in approximating the solution. This reduces specific joint differential vectors. The algorithm gives an exact solution away from the singularities and joint limits, and an approximate solution at or near the singularities and/or joint limits. The procedure is here implemented for a six d.o.f. teleoperator and a well behaved slave manipulator resulted under teleoperational control.

  19. Mixed lineage kinases (MLKs): a role in dendritic cells, inflammation and immunity?

    PubMed Central

    Handley, Matthew E; Rasaiyaah, Jane; Chain, Benjamin M; Katz, David R

    2007-01-01

    This review summarizes current knowledge about the mixed lineage kinases (MLKs) and explores their potential role in inflammation and immunity. MLKs were identified initially as signalling molecules in the nervous system. They were also shown to play a role in the cell cycle. Further studies documented three groups of MLKs, and showed that they may be activated via the c-Jun NH2 terminal kinase (JNK) pathway, and by Rho GTPases. The biochemistry of the MLKs has been investigated in considerable detail. Homodimerization and heterodimerization can occur, and both autophosphorylation and autoinhibition are seen. The interaction between MLKs and JNK interacting protein (JIP) scaffolds, and the resultant effects on mitogen activated protein kinases, have been identified. Clearly, there is some redundancy within the MLK pathway(s), since mice which lack the MLK3 molecule are not abnormal. However, using a combination of biochemical analysis and pharmacological inhibitors, several recent studies in vitro have suggested that MLKs are not only expressed in cells of the immune system (as well as in the nervous system), but also may be implicated selectively in the signalling pathway that follows on toll-like receptor ligation in innate sentinel cells, such as the dendritic cell. PMID:17408454

  20. Partially Redundant Enhancers Cooperatively Maintain Mammalian Pomc Expression Above a Critical Functional Threshold

    PubMed Central

    Lam, Daniel D.; de Souza, Flavio S. J.; Nasif, Sofia; Yamashita, Miho; López-Leal, Rodrigo; Meece, Kana; Sampath, Harini; Mercer, Aaron J.; Wardlaw, Sharon L.

    2015-01-01

    Cell-specific expression of many genes is conveyed by multiple enhancers, with each individual enhancer controlling a particular expression domain. In contrast, multiple enhancers drive similar expression patterns of some genes involved in embryonic development, suggesting regulatory redundancy. Work in Drosophila has indicated that functionally overlapping enhancers canalize development by buffering gene expression against environmental and genetic disturbances. However, little is known about regulatory redundancy in vertebrates and in genes mainly expressed during adulthood. Here we study nPE1 and nPE2, two phylogenetically conserved mammalian enhancers that drive expression of the proopiomelanocortin gene (Pomc) to the same set of hypothalamic neurons. The simultaneous deletion of both enhancers abolished Pomc expression at all ages and induced a profound metabolic dysfunction including early-onset extreme obesity. Targeted inactivation of either nPE1 or nPE2 led to very low levels of Pomc expression during early embryonic development indicating that both enhancers function synergistically. In adult mice, however, Pomc expression is controlled additively by both enhancers, with nPE1 being responsible for ∼80% and nPE2 for ∼20% of Pomc transcription. Consequently, nPE1 knockout mice exhibit mild obesity whereas nPE2-deficient mice maintain a normal body weight. These results suggest that nPE2-driven Pomc expression is compensated by nPE1 at later stages of development, essentially rescuing the earlier phenotype of nPE2 deficiency. Together, these results reveal that cooperative interactions between the enhancers confer robustness of Pomc expression against gene regulatory disturbances and preclude deleterious metabolic phenotypes caused by Pomc deficiency in adulthood. Thus, our study demonstrates that enhancer redundancy can be used by genes that control adult physiology in mammals and underlines the potential significance of regulatory sequence mutations in common diseases. PMID:25671638

  1. Backup Attitude Control Algorithms for the MAP Spacecraft

    NASA Technical Reports Server (NTRS)

    ODonnell, James R., Jr.; Andrews, Stephen F.; Ericsson-Jackson, Aprille J.; Flatley, Thomas W.; Ward, David K.; Bay, P. Michael

    1999-01-01

    The Microwave Anisotropy Probe (MAP) is a follow-on to the Differential Microwave Radiometer (DMR) instrument on the Cosmic Background Explorer (COBE) spacecraft. The MAP spacecraft will perform its mission, studying the early origins of the universe, in a Lissajous orbit around the Earth-Sun L(sub 2) Lagrange point. Due to limited mass, power, and financial resources, a traditional reliability concept involving fully redundant components was not feasible. This paper will discuss the redundancy philosophy used on MAP, describe the hardware redundancy selected (and why), and present backup modes and algorithms that were designed in lieu of additional attitude control hardware redundancy to improve the odds of mission success. Three of these modes have been implemented in the spacecraft flight software. The first onboard mode allows the MAP Kalman filter to be used with digital sun sensor (DSS) derived rates, in case of the failure of one of MAP's two two-axis inertial reference units. Similarly, the second onboard mode allows a star tracker only mode, using attitude and derived rate from one or both of MAP's star trackers for onboard attitude determination and control. The last backup mode onboard allows a sun-line angle offset to be commanded that will allow solar radiation pressure to be used for momentum management and orbit stationkeeping. In addition to the backup modes implemented on the spacecraft, two backup algorithms have been developed in the event of less likely contingencies. One of these is an algorithm for implementing an alternative scan pattern to MAP's nominal dual-spin science mode using only one or two reaction wheels and thrusters. Finally, an algorithm has been developed that uses thruster one shots while in science mode for momentum management. This algorithm has been developed in case system momentum builds up faster than anticipated, to allow adequate momentum management while minimizing interruptions to science. In this paper, each mode and algorithm will be discussed, and simulation results presented.

  2. Markov Chains For Testing Redundant Software

    NASA Technical Reports Server (NTRS)

    White, Allan L.; Sjogren, Jon A.

    1990-01-01

    Preliminary design developed for validation experiment that addresses problems unique to assuring extremely high quality of multiple-version programs in process-control software. Approach takes into account inertia of controlled system in sense it takes more than one failure of control program to cause controlled system to fail. Verification procedure consists of two steps: experimentation (numerical simulation) and computation, with Markov model for each step.

  3. The Grace Commission's View of Federal Research and Development.

    ERIC Educational Resources Information Center

    Aines, Andrew A.

    1984-01-01

    Focuses on the information aspects of the Grace Commission's (President's Private Sector Survey on Cost Control) findings and recommendations contained in the report on federal research and development. Research project reporting and redundancy, database provided by National Technical Information Service, cost controls, and measuring research and…

  4. Gluconeogenesis in Leishmania mexicana: contribution of glycerol kinase, phosphoenolpyruvate carboxykinase, and pyruvate phosphate dikinase.

    PubMed

    Rodriguez-Contreras, Dayana; Hamilton, Nicklas

    2014-11-21

    Gluconeogenesis is an active pathway in Leishmania amastigotes and is essential for their survival within the mammalian cells. However, our knowledge about this pathway in trypanosomatids is very limited. We investigated the role of glycerol kinase (GK), phosphoenolpyruvate carboxykinase (PEPCK), and pyruvate phosphate dikinase (PPDK) in gluconeogenesis by generating the respective Leishmania mexicana Δgk, Δpepck, and Δppdk null mutants. Our results demonstrated that indeed GK, PEPCK, and PPDK are key players in the gluconeogenesis pathway in Leishmania, although stage-specific differences in their contribution to this pathway were found. GK participates in the entry of glycerol in promastigotes and amastigotes; PEPCK participates in the entry of aspartate in promastigotes, and PPDK is involved in the entry of alanine in amastigotes. Furthermore, the majority of alanine enters into the pathway via decarboxylation of pyruvate in promastigotes, whereas pathway redundancy is suggested for the entry of aspartate in amastigotes. Interestingly, we also found that l-lactate, an abundant glucogenic precursor in mammals, was used by Leishmania amastigotes to synthesize mannogen, entering the pathway through PPDK. On the basis of these new results, we propose a revision in the current model of gluconeogenesis in Leishmania, emphasizing the differences between amastigotes and promastigotes. This work underlines the importance of studying the trypanosomatid intracellular life cycle stages to gain a better understanding of the pathologies caused in humans. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Mechanical Backup For Fly-By-Wire Control System

    NASA Technical Reports Server (NTRS)

    Stewart, Eric C.

    1992-01-01

    Mechanical device eliminates need for redundant fly-by-wire subsystems. Main components are two linkages. One connected to control column in conventional, reversible control system. Other slides inside first linkage and connected to pilot's control wheel. In addition to aircraft applications, design used in control systems in which computer control desirable but safety backup systems required; for example, in boat rudders, engine controls in boats and automobiles, and controls in construction equipment.

  6. Functional Redundancy and Divergence within the Arabidopsis RETICULATA-RELATED Gene Family1[W][OA

    PubMed Central

    Pérez-Pérez, José Manuel; Esteve-Bruna, David; González-Bayón, Rebeca; Kangasjärvi, Saijaliisa; Caldana, Camila; Hannah, Matthew A.; Willmitzer, Lothar; Ponce, María Rosa; Micol, José Luis

    2013-01-01

    A number of Arabidopsis (Arabidopsis thaliana) mutants exhibit leaf reticulation, having green veins that stand out against paler interveinal tissues, fewer cells in the interveinal mesophyll, and normal perivascular bundle sheath cells. Here, to examine the basis of leaf reticulation, we analyzed the Arabidopsis RETICULATA-RELATED (RER) gene family, several members of which cause leaf reticulation when mutated. Although transcripts of RE, RER1, and RER3 were mainly detected in the bundle sheath cells of expanded leaves, functional RER3:GREEN FLUORESCENT PROTEIN was visualized in the chloroplast membranes of all photosynthetic cells. Leaf reticulation in the re and rer3 loss-of-function mutants occurred, along with accumulation of reactive oxygen species, in a photoperiod-dependent manner. A comparison of re and rer3 leaf messenger RNA expression profiles showed more than 200 genes were similarly misexpressed in both mutants. In addition, metabolic profiles of mature leaves revealed that several biosynthetic pathways downstream of pyruvate are altered in re and rer3. Double mutant analysis showed that only re rer1 and rer5 rer6 exhibited synergistic phenotypes, indicating functional redundancy. The redundancy between RE and its closest paralog, RER1, was confirmed by overexpressing RER1 in re mutants, which partially suppressed leaf reticulation. Our results show that RER family members can be divided into four functional modules with divergent functions. Moreover, these results provide insights into the origin of the reticulated phenotype, suggesting that the RER proteins functionally interconnect photoperiodic growth, amino acid homeostasis, and reactive oxygen species metabolism during Arabidopsis leaf growth. PMID:23596191

  7. A Minimal Set of Glycolytic Genes Reveals Strong Redundancies in Saccharomyces cerevisiae Central Metabolism

    PubMed Central

    Solis-Escalante, Daniel; Kuijpers, Niels G. A.; Barrajon-Simancas, Nuria; van den Broek, Marcel; Pronk, Jack T.

    2015-01-01

    As a result of ancestral whole-genome and small-scale duplication events, the genomes of Saccharomyces cerevisiae and many eukaryotes still contain a substantial fraction of duplicated genes. In all investigated organisms, metabolic pathways, and more particularly glycolysis, are specifically enriched for functionally redundant paralogs. In ancestors of the Saccharomyces lineage, the duplication of glycolytic genes is purported to have played an important role leading to S. cerevisiae's current lifestyle favoring fermentative metabolism even in the presence of oxygen and characterized by a high glycolytic capacity. In modern S. cerevisiae strains, the 12 glycolytic reactions leading to the biochemical conversion from glucose to ethanol are encoded by 27 paralogs. In order to experimentally explore the physiological role of this genetic redundancy, a yeast strain with a minimal set of 14 paralogs was constructed (the “minimal glycolysis” [MG] strain). Remarkably, a combination of a quantitative systems approach and semiquantitative analysis in a wide array of growth environments revealed the absence of a phenotypic response to the cumulative deletion of 13 glycolytic paralogs. This observation indicates that duplication of glycolytic genes is not a prerequisite for achieving the high glycolytic fluxes and fermentative capacities that are characteristic of S. cerevisiae and essential for many of its industrial applications and argues against gene dosage effects as a means of fixing minor glycolytic paralogs in the yeast genome. The MG strain was carefully designed and constructed to provide a robust prototrophic platform for quantitative studies and has been made available to the scientific community. PMID:26071034

  8. Arabidopsis homologs of retinoblastoma-associated protein 46/48 associate with a histone deacetylase to act redundantly in chromatin silencing.

    PubMed

    Gu, Xiaofeng; Jiang, Danhua; Yang, Wannian; Jacob, Yannick; Michaels, Scott D; He, Yuehui

    2011-11-01

    RNA molecules such as small-interfering RNAs (siRNAs) and antisense RNAs (asRNAs) trigger chromatin silencing of target loci. In the model plant Arabidopsis, RNA-triggered chromatin silencing involves repressive histone modifications such as histone deacetylation, histone H3 lysine-9 methylation, and H3 lysine-27 monomethylation. Here, we report that two Arabidopsis homologs of the human histone-binding proteins Retinoblastoma-Associated Protein 46/48 (RbAp46/48), known as MSI4 (or FVE) and MSI5, function in partial redundancy in chromatin silencing of various loci targeted by siRNAs or asRNAs. We show that MSI5 acts in partial redundancy with FVE to silence FLOWERING LOCUS C (FLC), which is a crucial floral repressor subject to asRNA-mediated silencing, FLC homologs, and other loci including transposable and repetitive elements which are targets of siRNA-directed DNA Methylation (RdDM). Both FVE and MSI5 associate with HISTONE DEACETYLASE 6 (HDA6) to form complexes and directly interact with the target loci, leading to histone deacetylation and transcriptional silencing. In addition, these two genes function in de novo CHH (H = A, T, or C) methylation and maintenance of symmetric cytosine methylation (mainly CHG methylation) at endogenous RdDM target loci, and they are also required for establishment of cytosine methylation in the previously unmethylated sequences directed by the RdDM pathway. This reveals an important functional divergence of the plant RbAp46/48 relatives from animal counterparts.

  9. 77 FR 28772 - Air Quality: Widespread Use for Onboard Refueling Vapor Recovery and Stage II Waiver

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-16

    ... required emissions control measure in Serious, Severe, and Extreme ozone nonattainment areas. Beginning... control on nearly all new highway vehicles since 2006. Over time, non- ORVR vehicles will continue to be replaced with ORVR vehicles. Stage II and ORVR emission control systems are redundant, and the EPA has...

  10. The Effects of Visual-Verbal Redundancy and Recaps on Television News Learning.

    ERIC Educational Resources Information Center

    Son, Jinok; Davie, William

    A study examined the effects of visual-verbal redundancy and recaps on learning from television news. Two factors were used: redundancy between the visual and audio channels, and the presence or absence of a recap. Manipulation of these factors created four conditions: (1) redundant pictures and words plus recap, (2) redundant pictures and words…

  11. Multidimensional, mapping-based complex wavelet transforms.

    PubMed

    Fernandes, Felix C A; van Spaendonck, Rutger L C; Burrus, C Sidney

    2005-01-01

    Although the discrete wavelet transform (DWT) is a powerful tool for signal and image processing, it has three serious disadvantages: shift sensitivity, poor directionality, and lack of phase information. To overcome these disadvantages, we introduce multidimensional, mapping-based, complex wavelet transforms that consist of a mapping onto a complex function space followed by a DWT of the complex mapping. Unlike other popular transforms that also mitigate DWT shortcomings, the decoupled implementation of our transforms has two important advantages. First, the controllable redundancy of the mapping stage offers a balance between degree of shift sensitivity and transform redundancy. This allows us to create a directional, nonredundant, complex wavelet transform with potential benefits for image coding systems. To the best of our knowledge, no other complex wavelet transform is simultaneously directional and nonredundant. The second advantage of our approach is the flexibility to use any DWT in the transform implementation. As an example, we exploit this flexibility to create the complex double-density DWT: a shift-insensitive, directional, complex wavelet transform with a low redundancy of (3M - 1)/(2M - 1) in M dimensions. No other transform achieves all these properties at a lower redundancy, to the best of our knowledge. By exploiting the advantages of our multidimensional, mapping-based complex wavelet transforms in seismic signal-processing applications, we have demonstrated state-of-the-art results.

  12. Design of a modular digital computer system

    NASA Technical Reports Server (NTRS)

    1980-01-01

    A Central Control Element (CCE) module which controls the Automatically Reconfigurable Modular System (ARMS) and allows both redundant processing and multi-computing in the same computer with real time mode switching, is discussed. The same hardware is used for either reliability enhancement, speed enhancement, or for a combination of both.

  13. Redundant unbalance compensation of an active magnetic bearing system

    NASA Astrophysics Data System (ADS)

    Hutterer, Markus; Kalteis, Gerald; Schrödl, Manfred

    2017-09-01

    To achieve a good running behavior of a magnetic levitated rotor, a well-developed position controller and different compensation methods are required. Two very important structures in this context are the reduction of the gyroscopic effect and the unbalance vibration. Both structures have in common that they need the angular velocity information for calculation. For industrial applications this information is normally provided by an angle sensor which is fixed on the rotor. The angle information is also necessary for the field oriented control of the electrical drive. The main drawback of external position sensors are the case of a breakdown or an error of the motor controller. Therefore, the magnetic bearing can get unstable, because no angular velocity information is provided. To overcome this problem the presented paper describes the development of a selfsensing unbalance rejection in combination with a selfsensing speed control of the motor controller. Selfsensing means in this context that no angle sensor is required for the unbalance or torque control. With such structures two redundant speed and angle information sources are available and can be used for the magnetic bearing and the motor controller without the usage of an angle sensor.

  14. Space and time in the context of equilibrium-point theory.

    PubMed

    Feldman, Anatol G

    2011-05-01

    Advances to the equilibrium-point (EP) theory and solutions to several classical problems of action and perception are suggested and discussed. Among them are (1) the posture-movement problem of how movements away from a stable posture can be made without evoking resistance of posture-stabilizing mechanisms resulting from intrinsic muscle and reflex properties; (2) the problem of kinesthesia or why our sense of limb position is fairly accurate despite ambiguous positional information delivered by proprioceptive and cutaneous signals; (3) the redundancy problems in the control of multiple muscles and degrees of freedom. Central to the EP hypothesis is the notion that there are specific neural structures that represent spatial frames of reference (FRs) selected by the brain in a task-specific way from a set of available FRs. The brain is also able to translate or/and rotate the selected FRs by modifying their major attributes-the origin, metrics, and orientation-and thus substantially influence, in a feed-forward manner, action and perception. The brain does not directly solve redundancy problems: it only limits the amount of redundancy by predetermining where, in spatial coordinates, a task-specific action should emerge and allows all motor elements, including the environment, to interact to deliver a unique action, thus solving the redundancy problem (natural selection of action). The EP theory predicts the existence of specific neurons associated with the control of different attributes of FRs and explains the role of mirror neurons in the inferior frontal gyrus and place cells in the hippocampus. WIREs Cogni Sci 2011 2 287-304 DOI: 10.1002/wcs.108 For further resources related to this article, please visit the WIREs website. Copyright © 2010 John Wiley & Sons, Ltd.

  15. Classification and Analysis of Regulatory Pathways Using Graph Property, Biochemical and Physicochemical Property, and Functional Property

    PubMed Central

    Cai, Yu-Dong; Chou, Kuo-Chen

    2011-01-01

    Given a regulatory pathway system consisting of a set of proteins, can we predict which pathway class it belongs to? Such a problem is closely related to the biological function of the pathway in cells and hence is quite fundamental and essential in systems biology and proteomics. This is also an extremely difficult and challenging problem due to its complexity. To address this problem, a novel approach was developed that can be used to predict query pathways among the following six functional categories: (i) “Metabolism”, (ii) “Genetic Information Processing”, (iii) “Environmental Information Processing”, (iv) “Cellular Processes”, (v) “Organismal Systems”, and (vi) “Human Diseases”. The prediction method was established trough the following procedures: (i) according to the general form of pseudo amino acid composition (PseAAC), each of the pathways concerned is formulated as a 5570-D (dimensional) vector; (ii) each of components in the 5570-D vector was derived by a series of feature extractions from the pathway system according to its graphic property, biochemical and physicochemical property, as well as functional property; (iii) the minimum redundancy maximum relevance (mRMR) method was adopted to operate the prediction. A cross-validation by the jackknife test on a benchmark dataset consisting of 146 regulatory pathways indicated that an overall success rate of 78.8% was achieved by our method in identifying query pathways among the above six classes, indicating the outcome is quite promising and encouraging. To the best of our knowledge, the current study represents the first effort in attempting to identity the type of a pathway system or its biological function. It is anticipated that our report may stimulate a series of follow-up investigations in this new and challenging area. PMID:21980418

  16. Species-specific disruption of STING-dependent antiviral cellular defenses by the Zika virus NS2B3 protease.

    PubMed

    Ding, Qiang; Gaska, Jenna M; Douam, Florian; Wei, Lei; Kim, David; Balev, Metodi; Heller, Brigitte; Ploss, Alexander

    2018-06-18

    The limited host tropism of numerous viruses causing disease in humans remains incompletely understood. One example is Zika virus (ZIKV), an RNA virus that has reemerged in recent years. Here, we demonstrate that ZIKV efficiently infects fibroblasts from humans, great apes, New and Old World monkeys, but not rodents. ZIKV infection in human-but not murine-cells impairs responses to agonists of the cGMP-AMP synthase/stimulator of IFN genes (cGAS/STING) signaling pathway, suggesting that viral mechanisms to evade antiviral defenses are less effective in rodent cells. Indeed, human, but not mouse, STING is subject to cleavage by proteases encoded by ZIKV, dengue virus, West Nile virus, and Japanese encephalitis virus, but not that of yellow fever virus. The protease cleavage site, located between positions 78/79 of human STING, is only partially conserved in nonhuman primates and rodents, rendering these orthologs resistant to degradation. Genetic disruption of STING increases the susceptibility of mouse-but not human-cells to ZIKV. Accordingly, expression of only mouse, not human, STING in murine STING knockout cells rescues the ZIKV suppression phenotype. STING-deficient mice, however, did not exhibit increased susceptibility, suggesting that other redundant antiviral pathways control ZIKV infection in vivo. Collectively, our data demonstrate that numerous RNA viruses evade cGAS/STING-dependent signaling and affirm the importance of this pathway in shaping the host range of ZIKV. Furthermore, our results explain-at least in part-the decreased permissivity of rodent cells to ZIKV, which could aid in the development of mice model with inheritable susceptibility to ZIKV and other flaviviruses.

  17. Patient-Customized Drug Combination Prediction and Testing for T-cell Prolymphocytic Leukemia Patients.

    PubMed

    He, Liye; Tang, Jing; Andersson, Emma I; Timonen, Sanna; Koschmieder, Steffen; Wennerberg, Krister; Mustjoki, Satu; Aittokallio, Tero

    2018-05-01

    The molecular pathways that drive cancer progression and treatment resistance are highly redundant and variable between individual patients with the same cancer type. To tackle this complex rewiring of pathway cross-talk, personalized combination treatments targeting multiple cancer growth and survival pathways are required. Here we implemented a computational-experimental drug combination prediction and testing (DCPT) platform for efficient in silico prioritization and ex vivo testing in patient-derived samples to identify customized synergistic combinations for individual cancer patients. DCPT used drug-target interaction networks to traverse the massive combinatorial search spaces among 218 compounds (a total of 23,653 pairwise combinations) and identified cancer-selective synergies by using differential single-compound sensitivity profiles between patient cells and healthy controls, hence reducing the likelihood of toxic combination effects. A polypharmacology-based machine learning modeling and network visualization made use of baseline genomic and molecular profiles to guide patient-specific combination testing and clinical translation phases. Using T-cell prolymphocytic leukemia (T-PLL) as a first case study, we show how the DCPT platform successfully predicted distinct synergistic combinations for each of the three T-PLL patients, each presenting with different resistance patterns and synergy mechanisms. In total, 10 of 24 (42%) of selective combination predictions were experimentally confirmed to show synergy in patient-derived samples ex vivo The identified selective synergies among approved drugs, including tacrolimus and temsirolimus combined with BCL-2 inhibitor venetoclax, may offer novel drug repurposing opportunities for treating T-PLL. Significance: An integrated use of functional drug screening combined with genomic and molecular profiling enables patient-customized prediction and testing of drug combination synergies for T-PLL patients. Cancer Res; 78(9); 2407-18. ©2018 AACR . ©2018 American Association for Cancer Research.

  18. Equifinality and its violations in a redundant system: multifinger accurate force production.

    PubMed

    Wilhelm, Luke; Zatsiorsky, Vladimir M; Latash, Mark L

    2013-10-01

    We explored a hypothesis that transient perturbations applied to a redundant system result in equifinality in the space of task-related performance variables but not in the space of elemental variables. The subjects pressed with four fingers and produced an accurate constant total force level. The "inverse piano" device was used to lift and lower one of the fingers smoothly. The subjects were instructed "not to intervene voluntarily" with possible force changes. Analysis was performed in spaces of finger forces and finger modes (hypothetical neural commands to fingers) as elemental variables. Lifting a finger led to an increase in its force and a decrease in the forces of the other three fingers; the total force increased. Lowering the finger back led to a drop in the force of the perturbed finger. At the final state, the sum of the variances of finger forces/modes computed across repetitive trials was significantly higher than the variance of the total force/mode. Most variance of the individual finger force/mode changes between the preperturbation and postperturbation states was compatible with constant total force. We conclude that a transient perturbation applied to a redundant system leads to relatively small variance in the task-related performance variable (equifinality), whereas in the space of elemental variables much more variance occurs that does not lead to total force changes. We interpret the results within a general theoretical scheme that incorporates the ideas of hierarchically organized control, control with referent configurations, synergic control, and the uncontrolled manifold hypothesis.

  19. Redundancy, Self-Motion, and Motor Control

    PubMed Central

    Martin, V.; Scholz, J. P.; Schöner, G.

    2011-01-01

    Outside the laboratory, human movement typically involves redundant effector systems. How the nervous system selects among the task-equivalent solutions may provide insights into how movement is controlled. We propose a process model of movement generation that accounts for the kinematics of goal-directed pointing movements performed with a redundant arm. The key element is a neuronal dynamics that generates a virtual joint trajectory. This dynamics receives input from a neuronal timer that paces end-effector motion along its path. Within this dynamics, virtual joint velocity vectors that move the end effector are dynamically decoupled from velocity vectors that do not. Moreover, the sensed real joint configuration is coupled back into this neuronal dynamics, updating the virtual trajectory so that it yields to task-equivalent deviations from the dynamic movement plan. Experimental data from participants who perform in the same task setting as the model are compared in detail to the model predictions. We discover that joint velocities contain a substantial amount of self-motion that does not move the end effector. This is caused by the low impedance of muscle joint systems and by coupling among muscle joint systems due to multiarticulatory muscles. Back-coupling amplifies the induced control errors. We establish a link between the amount of self-motion and how curved the end-effector path is. We show that models in which an inverse dynamics cancels interaction torques predict too little self-motion and too straight end-effector paths. PMID:19718817

  20. Extensive cargo identification reveals distinct biological roles of the 12 importin pathways.

    PubMed

    Kimura, Makoto; Morinaka, Yuriko; Imai, Kenichiro; Kose, Shingo; Horton, Paul; Imamoto, Naoko

    2017-01-24

    Vast numbers of proteins are transported into and out of the nuclei by approximately 20 species of importin-β family nucleocytoplasmic transport receptors. However, the significance of the multiple parallel transport pathways that the receptors constitute is poorly understood because only limited numbers of cargo proteins have been reported. Here, we identified cargo proteins specific to the 12 species of human import receptors with a high-throughput method that employs stable isotope labeling with amino acids in cell culture, an in vitro reconstituted transport system, and quantitative mass spectrometry. The identified cargoes illuminated the manner of cargo allocation to the receptors. The redundancies of the receptors vary widely depending on the cargo protein. Cargoes of the same receptor are functionally related to one another, and the predominant protein groups in the cargo cohorts differ among the receptors. Thus, the receptors are linked to distinct biological processes by the nature of their cargoes.

  1. Deep epistasis in human metabolism

    NASA Astrophysics Data System (ADS)

    Imielinski, Marcin; Belta, Calin

    2010-06-01

    We extend and apply a method that we have developed for deriving high-order epistatic relationships in large biochemical networks to a published genome-scale model of human metabolism. In our analysis we compute 33 328 reaction sets whose knockout synergistically disables one or more of 43 important metabolic functions. We also design minimal knockouts that remove flux through fumarase, an enzyme that has previously been shown to play an important role in human cancer. Most of these knockout sets employ more than eight mutually buffering reactions, spanning multiple cellular compartments and metabolic subsystems. These reaction sets suggest that human metabolic pathways possess a striking degree of parallelism, inducing "deep" epistasis between diversely annotated genes. Our results prompt specific chemical and genetic perturbation follow-up experiments that could be used to query in vivo pathway redundancy. They also suggest directions for future statistical studies of epistasis in genetic variation data sets.

  2. Search, capture and signal: games microtubules and centrosomes play.

    PubMed

    Schuyler, S C; Pellman, D

    2001-01-01

    Accurate distribution of the chromosomes in dividing cells requires coupling of cellular polarity cues with both the orientation of the mitotic spindle and cell cycle progression. Work in budding yeast has demonstrated that cytoplasmic dynein and the kinesin Kip3p define redundant pathways that ensure proper spindle orientation. Furthermore, it has been shown that the Kip3p pathway components Kar9p and Bim1p (Yeb1p) form a complex that provides a molecular link between cortical polarity cues and spindle microtubules. Recently, other studies indicated that the cortical localization of Kar9p depends upon actin cables and Myo2p, a type V myosin. In addition, a BUB2-dependent cell cycle checkpoint has been described that inhibits the mitotic exit network and cytokinesis until proper centrosome position is achieved. Combined, these studies provide molecular insight into how cells link cellular polarity, spindle position and cell cycle progression.

  3. Reconfigurable Fault Tolerance for FPGAs

    NASA Technical Reports Server (NTRS)

    Shuler, Robert, Jr.

    2010-01-01

    The invention allows a field-programmable gate array (FPGA) or similar device to be efficiently reconfigured in whole or in part to provide higher capacity, non-redundant operation. The redundant device consists of functional units such as adders or multipliers, configuration memory for the functional units, a programmable routing method, configuration memory for the routing method, and various other features such as block RAM, I/O (random access memory, input/output) capability, dedicated carry logic, etc. The redundant device has three identical sets of functional units and routing resources and majority voters that correct errors. The configuration memory may or may not be redundant, depending on need. For example, SRAM-based FPGAs will need some type of radiation-tolerant configuration memory, or they will need triple-redundant configuration memory. Flash or anti-fuse devices will generally not need redundant configuration memory. Some means of loading and verifying the configuration memory is also required. These are all components of the pre-existing redundant FPGA. This innovation modifies the voter to accept a MODE input, which specifies whether ordinary voting is to occur, or if redundancy is to be split. Generally, additional routing resources will also be required to pass data between sections of the device created by splitting the redundancy. In redundancy mode, the voters produce an output corresponding to the two inputs that agree, in the usual fashion. In the split mode, the voters select just one input and convey this to the output, ignoring the other inputs. In a dual-redundant system (as opposed to triple-redundant), instead of a voter, there is some means to latch or gate a state update only when both inputs agree. In this case, the invention would require modification of the latch or gate so that it would operate normally in redundant mode, and would separately latch or gate the inputs in non-redundant mode.

  4. High precision redundant robotic manipulator

    DOEpatents

    Young, Kar-Keung David

    1998-01-01

    A high precision redundant robotic manipulator for overcoming contents imposed by obstacles or imposed by a highly congested work space. One embodiment of the manipulator has four degrees of freedom and another embodiment has seven degreed of freedom. Each of the embodiments utilize a first selective compliant assembly robot arm (SCARA) configuration to provide high stiffness in the vertical plane, a second SCARA configuration to provide high stiffness in the horizontal plane. The seven degree of freedom embodiment also utilizes kinematic redundancy to provide the capability of avoiding obstacles that lie between the base of the manipulator and the end effector or link of the manipulator. These additional three degrees of freedom are added at the wrist link of the manipulator to provide pitch, yaw and roll. The seven degrees of freedom embodiment uses one revolute point per degree of freedom. For each of the revolute joints, a harmonic gear coupled to an electric motor is introduced, and together with properly designed based servo controllers provide an end point repeatability of less than 10 microns.

  5. Pathway Distiller - multisource biological pathway consolidation

    PubMed Central

    2012-01-01

    Background One method to understand and evaluate an experiment that produces a large set of genes, such as a gene expression microarray analysis, is to identify overrepresentation or enrichment for biological pathways. Because pathways are able to functionally describe the set of genes, much effort has been made to collect curated biological pathways into publicly accessible databases. When combining disparate databases, highly related or redundant pathways exist, making their consolidation into pathway concepts essential. This will facilitate unbiased, comprehensive yet streamlined analysis of experiments that result in large gene sets. Methods After gene set enrichment finds representative pathways for large gene sets, pathways are consolidated into representative pathway concepts. Three complementary, but different methods of pathway consolidation are explored. Enrichment Consolidation combines the set of the pathways enriched for the signature gene list through iterative combining of enriched pathways with other pathways with similar signature gene sets; Weighted Consolidation utilizes a Protein-Protein Interaction network based gene-weighting approach that finds clusters of both enriched and non-enriched pathways limited to the experiments' resultant gene list; and finally the de novo Consolidation method uses several measurements of pathway similarity, that finds static pathway clusters independent of any given experiment. Results We demonstrate that the three consolidation methods provide unified yet different functional insights of a resultant gene set derived from a genome-wide profiling experiment. Results from the methods are presented, demonstrating their applications in biological studies and comparing with a pathway web-based framework that also combines several pathway databases. Additionally a web-based consolidation framework that encompasses all three methods discussed in this paper, Pathway Distiller (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow researchers access to the methods and example microarray data described in this manuscript, and the ability to analyze their own gene list by using our unique consolidation methods. Conclusions By combining several pathway systems, implementing different, but complementary pathway consolidation methods, and providing a user-friendly web-accessible tool, we have enabled users the ability to extract functional explanations of their genome wide experiments. PMID:23134636

  6. Pathway Distiller - multisource biological pathway consolidation.

    PubMed

    Doderer, Mark S; Anguiano, Zachry; Suresh, Uthra; Dashnamoorthy, Ravi; Bishop, Alexander J R; Chen, Yidong

    2012-01-01

    One method to understand and evaluate an experiment that produces a large set of genes, such as a gene expression microarray analysis, is to identify overrepresentation or enrichment for biological pathways. Because pathways are able to functionally describe the set of genes, much effort has been made to collect curated biological pathways into publicly accessible databases. When combining disparate databases, highly related or redundant pathways exist, making their consolidation into pathway concepts essential. This will facilitate unbiased, comprehensive yet streamlined analysis of experiments that result in large gene sets. After gene set enrichment finds representative pathways for large gene sets, pathways are consolidated into representative pathway concepts. Three complementary, but different methods of pathway consolidation are explored. Enrichment Consolidation combines the set of the pathways enriched for the signature gene list through iterative combining of enriched pathways with other pathways with similar signature gene sets; Weighted Consolidation utilizes a Protein-Protein Interaction network based gene-weighting approach that finds clusters of both enriched and non-enriched pathways limited to the experiments' resultant gene list; and finally the de novo Consolidation method uses several measurements of pathway similarity, that finds static pathway clusters independent of any given experiment. We demonstrate that the three consolidation methods provide unified yet different functional insights of a resultant gene set derived from a genome-wide profiling experiment. Results from the methods are presented, demonstrating their applications in biological studies and comparing with a pathway web-based framework that also combines several pathway databases. Additionally a web-based consolidation framework that encompasses all three methods discussed in this paper, Pathway Distiller (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow researchers access to the methods and example microarray data described in this manuscript, and the ability to analyze their own gene list by using our unique consolidation methods. By combining several pathway systems, implementing different, but complementary pathway consolidation methods, and providing a user-friendly web-accessible tool, we have enabled users the ability to extract functional explanations of their genome wide experiments.

  7. Anti-obesity drugs: past, present and future

    PubMed Central

    Rodgers, R. John; Tschöp, Matthias H.; Wilding, John P. H.

    2012-01-01

    The ideal anti-obesity drug would produce sustained weight loss with minimal side effects. The mechanisms that regulate energy balance have substantial built-in redundancy, overlap considerably with other physiological functions, and are influenced by social, hedonic and psychological factors that limit the effectiveness of pharmacological interventions. It is therefore unsurprising that anti-obesity drug discovery programmes have been littered with false starts, failures in clinical development, and withdrawals due to adverse effects that were not fully appreciated at the time of launch. Drugs that target pathways in metabolic tissues, such as adipocytes, liver and skeletal muscle, have shown potential in preclinical studies but none has yet reached clinical development. Recent improvements in the understanding of peptidergic signalling of hunger and satiety from the gastrointestinal tract mediated by ghrelin, cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 (GLP-1), and of homeostatic mechanisms related to leptin and its upstream pathways in the hypothalamus, have opened up new possibilities. Although some have now reached clinical development, it is uncertain whether they will meet the strict regulatory hurdles required for licensing of an anti-obesity drug. However, GLP-1 receptor agonists have already succeeded in diabetes treatment and, owing to their attractive body-weight-lowering effects in humans, will perhaps also pave the way for other anti-obesity agents. To succeed in developing drugs that control body weight to the extent seen following surgical intervention, it seems obvious that a new paradigm is needed. In other therapeutic arenas, such as diabetes and hypertension, lower doses of multiple agents targeting different pathways often yield better results than strategies that modify one pathway alone. Some combination approaches using peptides and small molecules have now reached clinical trials, although recent regulatory experience suggests that large challenges lie ahead. In future, this polytherapeutic strategy could possibly rival surgery in terms of efficacy, safety and sustainability of weight loss. PMID:22915024

  8. Novel therapeutic Strategies for Targeting Liver Cancer Stem Cells

    PubMed Central

    Oishi, Naoki; Wang, Xin Wei

    2011-01-01

    The cancer stem cell (CSC) hypothesis was first proposed over 40 years ago. Advances in CSC isolation were first achieved in hematological malignancies, with the first CSC demonstrated in acute myeloid leukemia. However, using similar strategies and technologies, and taking advantage of available surface markers, CSCs have been more recently demonstrated in a growing range of epithelial and other solid organ malignancies, suggesting that the majority of malignancies are dependent on such a compartment. Primary liver cancer consists predominantly of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). It is believed that hepatic progenitor cells (HPCs) could be the origin of some HCCs and ICCs. Furthermore, stem cell activators such as Wnt/β-catenin, TGF-β, Notch and Hedgehog signaling pathways also expedite tumorigenesis, and these pathways could serve as molecular targets to assist in designing cancer prevention strategies. Recent studies indicate that additional factors such as EpCAM, Lin28 or miR-181 may also contribute to HCC progression by targeting HCC CSCs. Various therapeutic drugs that directly modulate CSCs have been examined in vivo and in vitro. However, CSCs clearly have a complex pathogenesis, with a considerable crosstalk and redundancy in signaling pathways, and hence targeting single molecules or pathways may have a limited benefit for treatment. Many of the key signaling molecules are shared by both CSCs and normal stem cells, which add further challenges for designing molecularly targeted strategies specific to CSCs but sparing normal stem cells to avoid side effects. In addition to the direct control of CSCs, many other factors that are needed for the maintenance of CSCs, such as angiogenesis, vasculogenesis, invasion and migration, hypoxia, immune evasion, multiple drug resistance, and radioresistance, should be taken into consideration when designing therapeutic strategies for HCC. Here we provide a brief review of molecular signaling in liver CSCs and present insights into new therapeutic strategies for targeting liver CSCs. PMID:21552419

  9. Quantum Darwinism: Entanglement, branches, and the emergent classicality of redundantly stored quantum information

    NASA Astrophysics Data System (ADS)

    Blume-Kohout, Robin; Zurek, Wojciech H.

    2006-06-01

    We lay a comprehensive foundation for the study of redundant information storage in decoherence processes. Redundancy has been proposed as a prerequisite for objectivity, the defining property of classical objects. We consider two ensembles of states for a model universe consisting of one system and many environments: the first consisting of arbitrary states, and the second consisting of “singly branching” states consistent with a simple decoherence model. Typical states from the random ensemble do not store information about the system redundantly, but information stored in branching states has a redundancy proportional to the environment’s size. We compute the specific redundancy for a wide range of model universes, and fit the results to a simple first-principles theory. Our results show that the presence of redundancy divides information about the system into three parts: classical (redundant); purely quantum; and the borderline, undifferentiated or “nonredundant,” information.

  10. An efficient approach for inverse kinematics and redundancy resolution scheme of hyper-redundant manipulators

    NASA Astrophysics Data System (ADS)

    Chembuly, V. V. M. J. Satish; Voruganti, Hari Kumar

    2018-04-01

    Hyper redundant manipulators have a large number of degrees of freedom (DOF) than the required to perform a given task. Additional DOF of manipulators provide the flexibility to work in highly cluttered environment and in constrained workspaces. Inverse kinematics (IK) of hyper-redundant manipulators is complicated due to large number of DOF and these manipulators have multiple IK solutions. The redundancy gives a choice of selecting best solution out of multiple solutions based on certain criteria such as obstacle avoidance, singularity avoidance, joint limit avoidance and joint torque minimization. This paper focuses on IK solution and redundancy resolution of hyper-redundant manipulator using classical optimization approach. Joint positions are computed by optimizing various criteria for a serial hyper redundant manipulators while traversing different paths in the workspace. Several cases are addressed using this scheme to obtain the inverse kinematic solution while optimizing the criteria like obstacle avoidance, joint limit avoidance.

  11. De Novo Transcriptome Analysis of Medicinally Important Plantago ovata Using RNA-Seq

    PubMed Central

    Kotwal, Shivanjali; Kaul, Sanjana; Sharma, Pooja; Gupta, Mehak; Shankar, Rama; Jain, Mukesh; Dhar, Manoj K.

    2016-01-01

    Plantago ovata is an economically and medicinally important plant of the family Plantaginaceae. It is used extensively for the production of seed husk for its application in pharmaceutical, food and cosmetic industries. In the present study, the transcriptome of P. ovata ovary was sequenced using Illumina Genome Analyzer platform to characterize the mucilage biosynthesis pathway in the plant. De novo assembly was carried out using Oases followed by velvet. A total of 46,955 non-redundant transcripts (≥100 bp) using ~29 million high-quality paired end reads were generated. Functional categorization of these transcripts revealed the presence of several genes involved in various biological processes like metabolic pathways, mucilage biosynthesis, biosynthesis of secondary metabolites and antioxidants. In addition, simple sequence-repeat motifs, non-coding RNAs and transcription factors were also identified. Expression profiling of some genes involved in mucilage biosynthetic pathway was performed in different tissues of P. ovata using Real time PCR analysis. The study has resulted in a valuable resource for further studies on gene expression, genomics and functional genomics in P. ovata. PMID:26943165

  12. The paradigm of IL-6: from basic science to medicine.

    PubMed

    Naka, Tetsuji; Nishimoto, Norihiro; Kishimoto, Tadamitsu

    2002-01-01

    IL-6 is a pleiotropic cytokine with a wide range of biological activities in immune regulation, hematopoiesis, inflammation, and oncogenesis. Its activities are shared by IL-6-related cytokines such as leukemia inhibitory factor and oncostatin M. The pleiotropy and redundancy of IL-6 functions have been identified by using a unique receptor system comprising two functional proteins: an IL-6 receptor (IL-6R) and gp130, the common signal transducer of cytokines related to IL-6. Signal transduction through gp130 is mediated by two pathways: the JAK-STAT (Janus family tyrosine kinase-signal transducer and activator of transcription) pathway and the Ras mitogen-activated protein kinase pathway. The negative regulators of IL-6 signaling have also been identified, although the physiological roles of the molecules are not yet fully understood. The pathological roles of IL-6 have also been clarified in various disease conditions, such as inflammatory, autoimmune, and malignant diseases. On the basis of the findings, a new therapeutic approach to block the IL-6 signal using humanized anti-IL-6R antibody for rheumatoid arthritis, Castleman's disease, and multiple myeloma has been attempted.

  13. Regulation of Manganese Antioxidants by Nutrient Sensing Pathways in Saccharomyces cerevisiae

    PubMed Central

    Reddi, Amit R.; Culotta, Valeria C.

    2011-01-01

    In aerobic organisms, protection from oxidative damage involves the combined action of enzymatic and nonproteinaceous cellular factors that collectively remove harmful reactive oxygen species. One class of nonproteinaceous antioxidants includes small molecule complexes of manganese (Mn) that can scavenge superoxide anion radicals and provide a backup for superoxide dismutase enzymes. Such Mn antioxidants have been identified in diverse organisms; however, nothing regarding their physiology in the context of cellular adaptation to stress was known. Using a molecular genetic approach in Bakers’ yeast, Saccharomyces cerevisiae, we report that the Mn antioxidants can fall under control of the same pathways used for nutrient sensing and stress responses. Specifically, a serine/threonine PAS-kinase, Rim15p, that is known to integrate phosphate, nitrogen, and carbon sensing, can also control Mn antioxidant activity in yeast. Rim15p is negatively regulated by the phosphate-sensing kinase complex Pho80p/Pho85p and by the nitrogen-sensing Akt/S6 kinase homolog, Sch9p. We observed that loss of either of these upstream kinase sensors dramatically inhibited the potency of Mn as an antioxidant. Downstream of Rim15p are transcription factors Gis1p and the redundant Msn2/Msn4p pair that typically respond to nutrient and stress signals. Both transcription factors were found to modulate the potency of the Mn antioxidant but in opposing fashions: loss of Gis1p was seen to enhance Mn antioxidant activity whereas loss of Msn2/4p greatly suppressed it. Our observed roles for nutrient and stress response kinases and transcription factors in regulating the Mn antioxidant underscore its physiological importance in aerobic fitness. PMID:21926297

  14. Arabidopsis bHLH100 and bHLH101 Control Iron Homeostasis via a FIT-Independent Pathway

    PubMed Central

    Sivitz, Alicia B.; Hermand, Victor; Curie, Catherine; Vert, Grégory

    2012-01-01

    Iron deficiency induces a complex set of responses in plants, including developmental and physiological changes, to increase iron uptake from soil. In Arabidopsis, many transporters involved in the absorption and distribution of iron have been identified over the past decade. However, little is known about the signaling pathways and networks driving the various responses to low iron. Only the basic helix–loop–helix (bHLH) transcription factor FIT has been shown to control the expression of the root iron uptake machinery genes FRO2 and IRT1. Here, we characterize the biological role of two other iron-regulated transcription factors, bHLH100 and bHLH101, in iron homeostasis. First direct transcriptional targets of FIT were determined in vivo. We show that bHLH100 and bHLH101 do not regulate FIT target genes, suggesting that they play a non-redundant role with the two closely related bHLH factors bHLH038 and bHLH039 that have been suggested to act in concert with FIT. bHLH100 and bHLH101 play a crucial role in iron-deficiency responses, as attested by their severe growth defects and iron homeostasis related phenotypes on low-iron media. To gain further insight into the biological role of bHLH100 and bHLH101, we performed microarray analysis using the corresponding double mutant and showed that bHLH100 and bHLH101 likely regulate genes involved in the distribution of iron within the plant. Altogether, this work establishes bHLH100 and bHLH101 as key regulators of iron-deficiency responses independent of the master regulator FIT and sheds light on new regulatory networks important for proper growth and development under low iron conditions. PMID:22984573

  15. 20 years of leptin: leptin and reproduction: past milestones, present undertakings, and future endeavors.

    PubMed

    Chehab, Farid F

    2014-10-01

    The association between leptin and reproduction originated with the leptin-mediated correction of sterility in ob/ob mice and initiation of reproductive function in normal female mice. The uncovering of a central leptin pathway regulating food intake prompted the dissection of neuroendocrine mechanisms involving leptin in the metabolic control of reproduction. The absence of leptin receptors on GnRH neurons incited a search for intermediary neurons situated between leptin-responsive and GnRH neurons. This review addresses the most significant findings that have furthered our understanding of recent progress in this new field. The role of leptin in puberty was impacted by the discovery of neurons that co-express kisspeptin, neurokinin B, and dynorphin and these could act as leptin intermediates. Furthermore, the identification of first-order leptin-responsive neurons in the premammilary ventral nucleus and other brain regions opens new avenues to explore their relationship to GnRH neurons. Central to these advances is the unveiling that agouti-related protein/neuropeptide Y neurons project onto GnRH and kisspeptin neurons, allowing for a crosstalk between food intake and reproduction. Finally, while puberty is a state of leptin sensitivity, mid-gestation represents a state of leptin resistance aimed at building energy stores to sustain pregnancy and lactation. The mechanisms underlying leptin resistance in pregnancy have lagged; however, the establishment of this natural state is significant. Reproduction and energy balance are tightly controlled and backed up by redundant mechanisms that are critical for the survival of our species. It will be the goal of the following decade to shed new light on these complex and essential pathways. © 2014 Society for Endocrinology.

  16. 77 FR 5862 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-06

    ... subscribers only): Per 64kb increase above $200/month. 128kb Tl base. Option 1, 2, or 3 with Fee for Option 1.../month. redundancy), dual hubs (one for redundancy), and dual router (one for redundancy). Option 3: Dual Tl lines (one for $2,500/month. redundancy), dual hubs (one for redundancy), and dual routers (one...

  17. Reduced Precision Redundancy Applied to Arithmetic Operations in Field Programmable Gate Arrays for Satellite Control and Sensor Systems

    DTIC Science & Technology

    2008-12-01

    Figure 2. Definition of Attitude Angles and Torque Components in Spacecraft Reference Frame...Figure 5. PD controller in ideal three-axis-stabilized spacecraft ADCS. ................................16 Figure 6. Extract Position Angles function in...performance of spacecraft systems. Two categories of system architectures are discussed: recursive data management, found in feedback control systems; and

  18. Linear Quadratic Tracking Design for a Generic Transport Aircraft with Structural Load Constraints

    NASA Technical Reports Server (NTRS)

    Burken, John J.; Frost, Susan A.; Taylor, Brian R.

    2011-01-01

    When designing control laws for systems with constraints added to the tracking performance, control allocation methods can be utilized. Control allocations methods are used when there are more command inputs than controlled variables. Constraints that require allocators are such task as; surface saturation limits, structural load limits, drag reduction constraints or actuator failures. Most transport aircraft have many actuated surfaces compared to the three controlled variables (such as angle of attack, roll rate & angle of side slip). To distribute the control effort among the redundant set of actuators a fixed mixer approach can be utilized or online control allocation techniques. The benefit of an online allocator is that constraints can be considered in the design whereas the fixed mixer cannot. However, an online control allocator mixer has a disadvantage of not guaranteeing a surface schedule, which can then produce ill defined loads on the aircraft. The load uncertainty and complexity has prevented some controller designs from using advanced allocation techniques. This paper considers actuator redundancy management for a class of over actuated systems with real-time structural load limits using linear quadratic tracking applied to the generic transport model. A roll maneuver example of an artificial load limit constraint is shown and compared to the same no load limitation maneuver.

  19. Hybrid Analytical and Data-Driven Modeling for Feed-Forward Robot Control †

    PubMed Central

    Reinhart, René Felix; Shareef, Zeeshan; Steil, Jochen Jakob

    2017-01-01

    Feed-forward model-based control relies on models of the controlled plant, e.g., in robotics on accurate knowledge of manipulator kinematics or dynamics. However, mechanical and analytical models do not capture all aspects of a plant’s intrinsic properties and there remain unmodeled dynamics due to varying parameters, unmodeled friction or soft materials. In this context, machine learning is an alternative suitable technique to extract non-linear plant models from data. However, fully data-based models suffer from inaccuracies as well and are inefficient if they include learning of well known analytical models. This paper thus argues that feed-forward control based on hybrid models comprising an analytical model and a learned error model can significantly improve modeling accuracy. Hybrid modeling here serves the purpose to combine the best of the two modeling worlds. The hybrid modeling methodology is described and the approach is demonstrated for two typical problems in robotics, i.e., inverse kinematics control and computed torque control. The former is performed for a redundant soft robot and the latter for a rigid industrial robot with redundant degrees of freedom, where a complete analytical model is not available for any of the platforms. PMID:28208697

  20. Hybrid Analytical and Data-Driven Modeling for Feed-Forward Robot Control.

    PubMed

    Reinhart, René Felix; Shareef, Zeeshan; Steil, Jochen Jakob

    2017-02-08

    Feed-forward model-based control relies on models of the controlled plant, e.g., in robotics on accurate knowledge of manipulator kinematics or dynamics. However, mechanical and analytical models do not capture all aspects of a plant's intrinsic properties and there remain unmodeled dynamics due to varying parameters, unmodeled friction or soft materials. In this context, machine learning is an alternative suitable technique to extract non-linear plant models from data. However, fully data-based models suffer from inaccuracies as well and are inefficient if they include learning of well known analytical models. This paper thus argues that feed-forward control based on hybrid models comprising an analytical model and a learned error model can significantly improve modeling accuracy. Hybrid modeling here serves the purpose to combine the best of the two modeling worlds. The hybrid modeling methodology is described and the approach is demonstrated for two typical problems in robotics, i.e., inverse kinematics control and computed torque control. The former is performed for a redundant soft robot and the latter for a rigid industrial robot with redundant degrees of freedom, where a complete analytical model is not available for any of the platforms.

  1. Proximity operations considerations affecting spacecraft design

    NASA Technical Reports Server (NTRS)

    Staas, Steven K.

    1991-01-01

    Proximity operations can be defined as the maneuvering of two or more spacecraft within 1 nautical mile range, with relative velocity less than 10 feet per second. The passive vehicle is nontranslating and should provide for maintenance of the desired approach attitude. It must accommodate the active (translating) vehicle induced structural loads and performance characteristics (mating hardware tolerances), and support sensor compatibility (transponder, visual targets, etc.). The active vehicle must provide adequate sensor systems (relative state information, field-of-view, redundancy), flight control hardware (thruster sizing, minimal cross-coupling, performance margins, redundancy) and software (reconfigurable, attitude/rate modes, translation and rotation fine control authority) characteristic, and adequate non-propulsive consumables such as power. Operational concerns must be considered. These include the following: (1) the desired approach trajectory and relative orientation; (2) the active vehicle thruster plume effects (forces, torques, contamination) on the passive vehicle; and (3) procedures for contingencies such as loss of communications, sensor or propulsion failures, and target vehicle loss of control.

  2. Targeted Deletion of a Plasmodium Site-2 Protease Impairs Life Cycle Progression in the Mammalian Host

    PubMed Central

    Goulielmaki, Evi; Chalari, Anna; Withers-Martinez, Chrislaine; Siden-Kiamos, Inga; Matuschewski, Kai

    2017-01-01

    Site-2 proteases (S2P) belong to the M50 family of metalloproteases, which typically perform essential roles by mediating activation of membrane–bound transcription factors through regulated intramembrane proteolysis (RIP). Protease-dependent liberation of dormant transcription factors triggers diverse cellular responses, such as sterol regulation, Notch signalling and the unfolded protein response. Plasmodium parasites rely on regulated proteolysis for controlling essential pathways throughout the life cycle. In this study we examine the Plasmodium-encoded S2P in a murine malaria model and show that it is expressed in all stages of Plasmodium development. Localisation studies by endogenous gene tagging revealed that in all invasive stages the protein is in close proximity to the nucleus. Ablation of PbS2P by reverse genetics leads to reduced growth rates during liver and blood infection and, hence, virulence attenuation. Strikingly, absence of PbS2P was compatible with parasite life cycle progression in the mosquito and mammalian hosts under physiological conditions, suggesting redundant or dispensable roles in vivo. PMID:28107409

  3. Targeted Deletion of a Plasmodium Site-2 Protease Impairs Life Cycle Progression in the Mammalian Host.

    PubMed

    Koussis, Konstantinos; Goulielmaki, Evi; Chalari, Anna; Withers-Martinez, Chrislaine; Siden-Kiamos, Inga; Matuschewski, Kai; Loukeris, Thanasis G

    2017-01-01

    Site-2 proteases (S2P) belong to the M50 family of metalloproteases, which typically perform essential roles by mediating activation of membrane-bound transcription factors through regulated intramembrane proteolysis (RIP). Protease-dependent liberation of dormant transcription factors triggers diverse cellular responses, such as sterol regulation, Notch signalling and the unfolded protein response. Plasmodium parasites rely on regulated proteolysis for controlling essential pathways throughout the life cycle. In this study we examine the Plasmodium-encoded S2P in a murine malaria model and show that it is expressed in all stages of Plasmodium development. Localisation studies by endogenous gene tagging revealed that in all invasive stages the protein is in close proximity to the nucleus. Ablation of PbS2P by reverse genetics leads to reduced growth rates during liver and blood infection and, hence, virulence attenuation. Strikingly, absence of PbS2P was compatible with parasite life cycle progression in the mosquito and mammalian hosts under physiological conditions, suggesting redundant or dispensable roles in vivo.

  4. Decomposition of complex microbial behaviors into resource-based stress responses

    PubMed Central

    Carlson, Ross P.

    2009-01-01

    Motivation: Highly redundant metabolic networks and experimental data from cultures likely adapting simultaneously to multiple stresses can complicate the analysis of cellular behaviors. It is proposed that the explicit consideration of these factors is critical to understanding the competitive basis of microbial strategies. Results: Wide ranging, seemingly unrelated Escherichia coli physiological fluxes can be simply and accurately described as linear combinations of a few ecologically relevant stress adaptations. These strategies were identified by decomposing the central metabolism of E.coli into elementary modes (mathematically defined biochemical pathways) and assessing the resource investment cost–benefit properties for each pathway. The approach capitalizes on the inherent tradeoffs related to investing finite resources like nitrogen into different pathway enzymes when the pathways have varying metabolic efficiencies. The subset of ecologically competitive pathways represented 0.02% of the total permissible pathways. The biological relevance of the assembled strategies was tested against 10 000 randomly constructed pathway subsets. None of the randomly assembled collections were able to describe all of the considered experimental data as accurately as the cost-based subset. The results suggest these metabolic strategies are biologically significant. The current descriptions were compared with linear programming (LP)-based flux descriptions using the Euclidean distance metric. The current study's pathway subset described the experimental fluxes with better accuracy than the LP results without having to test multiple objective functions or constraints and while providing additional ecological insight into microbial behavior. The assembled pathways seem to represent a generalized set of strategies that can describe a wide range of microbial responses and hint at evolutionary processes where a handful of successful metabolic strategies are utilized simultaneously in different combinations to adapt to diverse conditions. Contact: rossc@biofilms.montana.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19008248

  5. Performance Evaluation of Reliable Multicast Protocol for Checkout and Launch Control Systems

    NASA Technical Reports Server (NTRS)

    Shu, Wei Wennie; Porter, John

    2000-01-01

    The overall objective of this project is to study reliability and performance of Real Time Critical Network (RTCN) for checkout and launch control systems (CLCS). The major tasks include reliability and performance evaluation of Reliable Multicast (RM) package and fault tolerance analysis and design of dual redundant network architecture.

  6. Configuration Control of a Mobile Dextrous Robot: Real-Time Implementation and Experimentation

    NASA Technical Reports Server (NTRS)

    Lim, David; Seraji, Homayoun

    1996-01-01

    This paper describes the design and implementation of a real-time control system with multiple modes of operation for a mobile dexterous manipulator. The manipulator under study is a kinematically redundant seven degree-of-freedom arm from Robotics Research Corporation, mounted on a one degree-of-freedom motorized platform.

  7. Robust Task Space Trajectory Tracking Control of Robotic Manipulators

    NASA Astrophysics Data System (ADS)

    Galicki, M.

    2016-08-01

    This work deals with the problem of the accurate task space trajectory tracking subject to finite-time convergence. Kinematic and dynamic equations of a redundant manipulator are assumed to be uncertain. Moreover, globally unbounded disturbances are allowed to act on the manipulator when tracking the trajectory by the end-effector. Furthermore, the movement is to be accomplished in such a way as to reduce both the manipulator torques and their oscillations thus eliminating the potential robot vibrations. Based on suitably defined task space non-singular terminal sliding vector variable and the Lyapunov stability theory, we propose a class of chattering-free robust controllers, based on the estimation of transpose Jacobian, which seem to be effective in counteracting both uncertain kinematics and dynamics, unbounded disturbances and (possible) kinematic and/or algorithmic singularities met on the robot trajectory. The numerical simulations carried out for a redundant manipulator of a SCARA type consisting of the three revolute kinematic pairs and operating in a two-dimensional task space, illustrate performance of the proposed controllers as well as comparisons with other well known control schemes.

  8. Transmembrane Proteins UNC-40/DCC, PTP-3/LAR, and MIG-21 Control Anterior–Posterior Neuroblast Migration with Left–Right Functional Asymmetry in Caenorhabditis elegans

    PubMed Central

    Sundararajan, Lakshmi; Lundquist, Erik A.

    2012-01-01

    Migration of neurons and neural crest cells is of central importance to the development of nervous systems. In Caenorhabditis elegans, the QL neuroblast on the left migrates posteriorly, and QR on the right migrates anteriorly, despite similar lineages and birth positions with regard to the left–right axis. Initial migration is independent of a Wnt signal that controls later anterior–posterior Q descendant migration. Previous studies showed that the transmembrane proteins UNC-40/DCC and MIG-21, a novel thrombospondin type I repeat containing protein, act redundantly in left-side QL posterior migration. Here we show that the LAR receptor protein tyrosine phosphatase PTP-3 acts with MIG-21 in parallel to UNC-40 in QL posterior migration. We also show that in right-side QR, the UNC-40 and PTP-3/MIG-21 pathways mutually inhibit each other’s role in posterior migration, allowing anterior QR migration. Finally, we present evidence that these proteins act autonomously in the Q neuroblasts. These studies indicate an inherent left–right asymmetry in the Q neuroblasts with regard to UNC-40, PTP-3, and MIG-21 function that results in posterior vs. anterior migration. PMID:23051647

  9. The Rice Receptor-Like Kinases DWARF AND RUNTISH SPIKELET1 and 2 Repress Cell Death and Affect Sugar Utilization during Reproductive Development

    PubMed Central

    Song, Feng-Yan; Zhao, Ying; Wang, Chun-Yan; Zhang, Yong-Cun; Yang, Qian; Wang, Jiao; Bu, Shuo-Lei; Sun, Li-Jing; Zhang, Sheng-Wei; Zhang, Su-Qiao; Sun, Da-Ye

    2017-01-01

    Cell-to-cell communication precisely controls the creation of new organs during reproductive growth. However, the sensor molecules that mediate developmental signals in monocot plants are poorly understood. Here, we report that DWARF AND RUNTISH SPIKELET1 (DRUS1) and DRUS2, two closely related receptor-like kinases (RLKs), redundantly control reproductive growth and development in rice (Oryza sativa). A drus1-1 drus2 double knockout mutant, but not either single mutant, showed extreme dwarfism and barren inflorescences that harbored sterile spikelets. The gibberellin pathway was not impaired in this mutant. A phenotypic comparison of mutants expressing different amounts of DRUS1 and 2 revealed that reproductive growth requires a threshold level of DRUS1/2 proteins. DRUS1 and 2 maintain cell viability by repressing protease-mediated cell degradation and likely by affecting sugar utilization or conversion. In the later stages of anther development, survival of the endothecium requires DRUS1/2, which may stimulate expression of the UDP-glucose pyrophosphorylase gene UGP2 and starch biosynthesis in pollen. Unlike their Arabidopsis thaliana ortholog FERONIA, DRUS1 and 2 mediate a fundamental signaling process that is essential for cell survival and represents a novel biological function for the CrRLK1L RLK subfamily. PMID:28082384

  10. Evolutionary transitions in controls reconcile adaptation with continuity of evolution.

    PubMed

    Badyaev, Alexander V

    2018-05-19

    Evolution proceeds by accumulating functional solutions, necessarily forming an uninterrupted lineage from past solutions of ancestors to the current design of extant forms. At the population level, this process requires an organismal architecture in which the maintenance of local adaptation does not preclude the ability to innovate in the same traits and their continuous evolution. Representing complex traits as networks enables us to visualize a fundamental principle that resolves tension between adaptation and continuous evolution: phenotypic states encompassing adaptations traverse the continuous multi-layered landscape of past physical, developmental and functional associations among traits. The key concept that captures such traversing is network controllability - the ability to move a network from one state into another while maintaining its functionality (reflecting evolvability) and to efficiently propagate information or products through the network within a phenotypic state (maintaining its robustness). Here I suggest that transitions in network controllability - specifically in the topology of controls - help to explain how robustness and evolvability are balanced during evolution. I will focus on evolutionary transitions in degeneracy of metabolic networks - a ubiquitous property of phenotypic robustness where distinct pathways achieve the same end product - to suggest that associated changes in network controls is a common rule underlying phenomena as distinct as phenotypic plasticity, organismal accommodation of novelties, genetic assimilation, and macroevolutionary diversification. Capitalizing on well understood principles by which network structure translates into function of control nodes, I show that accumulating redundancy in one type of network controls inevitably leads to the emergence of another type of controls, forming evolutionary cycles of network controllability that, ultimately, reconcile local adaptation with continuity of evolution. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Three WRKY transcription factors additively repress abscisic acid and gibberellin signaling in aleurone cells.

    PubMed

    Zhang, Liyuan; Gu, Lingkun; Ringler, Patricia; Smith, Stanley; Rushton, Paul J; Shen, Qingxi J

    2015-07-01

    Members of the WRKY transcription factor superfamily are essential for the regulation of many plant pathways. Functional redundancy due to duplications of WRKY transcription factors, however, complicates genetic analysis by allowing single-mutant plants to maintain wild-type phenotypes. Our analyses indicate that three group I WRKY genes, OsWRKY24, -53, and -70, act in a partially redundant manner. All three showed characteristics of typical WRKY transcription factors: each localized to nuclei and yeast one-hybrid assays indicated that they all bind to W-boxes, including those present in their own promoters. Quantitative real time-PCR (qRT-PCR) analyses indicated that the expression levels of the three WRKY genes varied in the different tissues tested. Particle bombardment-mediated transient expression analyses indicated that all three genes repress the GA and ABA signaling in a dosage-dependent manner. Combination of all three WRKY genes showed additive antagonism of ABA and GA signaling. These results suggest that these WRKY proteins function as negative transcriptional regulators of GA and ABA signaling. However, different combinations of these WRKY genes can lead to varied strengths in suppression of their targets. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Functional Analogy in Human Metabolism: Enzymes with Different Biological Roles or Functional Redundancy?

    PubMed Central

    Piergiorge, Rafael Mina; de Miranda, Antonio Basílio; Catanho, Marcos

    2017-01-01

    Abstract Since enzymes catalyze almost all chemical reactions that occur in living organisms, it is crucial that genes encoding such activities are correctly identified and functionally characterized. Several studies suggest that the fraction of enzymatic activities in which multiple events of independent origin have taken place during evolution is substantial. However, this topic is still poorly explored, and a comprehensive investigation of the occurrence, distribution, and implications of these events has not been done so far. Fundamental questions, such as how analogous enzymes originate, why so many events of independent origin have apparently occurred during evolution, and what are the reasons for the coexistence in the same organism of distinct enzymatic forms catalyzing the same reaction, remain unanswered. Also, several isofunctional enzymes are still not recognized as nonhomologous, even with substantial evidence indicating different evolutionary histories. In this work, we begin to investigate the biological significance of the cooccurrence of nonhomologous isofunctional enzymes in human metabolism, characterizing functional analogous enzymes identified in metabolic pathways annotated in the human genome. Our hypothesis is that the coexistence of multiple enzymatic forms might not be interpreted as functional redundancy. Instead, these enzymatic forms may be implicated in distinct (and probably relevant) biological roles. PMID:28854631

  13. Tissue-Specific Profiling Reveals Transcriptome Alterations in Arabidopsis Mutants Lacking Morphological Phenotypes[C][W

    PubMed Central

    Simon, Marissa; Bruex, Angela; Kainkaryam, Raghunandan M.; Zheng, Xiaohua; Huang, Ling; Woolf, Peter J.; Schiefelbein, John

    2013-01-01

    Traditional genetic analysis relies on mutants with observable phenotypes. Mutants lacking visible abnormalities may nevertheless exhibit molecular differences useful for defining gene function. To examine this, we analyzed tissue-specific transcript profiles from Arabidopsis thaliana transcription factor gene mutants with known roles in root epidermis development, but lacking a single-gene mutant phenotype due to genetic redundancy. We discovered substantial transcriptional changes in each mutant, preferentially affecting root epidermal genes in a manner consistent with the known double mutant effects. Furthermore, comparing transcript profiles of single and double mutants, we observed remarkable variation in the sensitivity of target genes to the loss of one or both paralogous genes, including preferential effects on specific branches of the epidermal gene network, likely reflecting the pathways of paralog subfunctionalization during evolution. In addition, we analyzed the root epidermal transcriptome of the transparent testa glabra2 mutant to clarify its role in the network. These findings provide insight into the molecular basis of genetic redundancy and duplicate gene diversification at the level of a specific gene regulatory network, and they demonstrate the usefulness of tissue-specific transcript profiling to define gene function in mutants lacking informative visible changes in phenotype. PMID:24014549

  14. Human cytochromes P450 in health and disease

    PubMed Central

    Nebert, Daniel W.; Wikvall, Kjell; Miller, Walter L.

    2013-01-01

    There are 18 mammalian cytochrome P450 (CYP) families, which encode 57 genes in the human genome. CYP2, CYP3 and CYP4 families contain far more genes than the other 15 families; these three families are also the ones that are dramatically larger in rodent genomes. Most (if not all) genes in the CYP1, CYP2, CYP3 and CYP4 families encode enzymes involved in eicosanoid metabolism and are inducible by various environmental stimuli (i.e. diet, chemical inducers, drugs, pheromones, etc.), whereas the other 14 gene families often have only a single member, and are rarely if ever inducible or redundant. Although the CYP2 and CYP3 families can be regarded as largely redundant and promiscuous, mutations or other defects in one or more genes of the remaining 16 gene families are primarily the ones responsible for P450-specific diseases—confirming these genes are not superfluous or promiscuous but rather are more directly involved in critical life functions. P450-mediated diseases comprise those caused by: aberrant steroidogenesis; defects in fatty acid, cholesterol and bile acid pathways; vitamin D dysregulation and retinoid (as well as putative eicosanoid) dysregulation during fertilization, implantation, embryogenesis, foetogenesis and neonatal development. PMID:23297354

  15. A comparison of Heuristic method and Llewellyn’s rules for identification of redundant constraints

    NASA Astrophysics Data System (ADS)

    Estiningsih, Y.; Farikhin; Tjahjana, R. H.

    2018-03-01

    Important techniques in linear programming is modelling and solving practical optimization. Redundant constraints are consider for their effects on general linear programming problems. Identification and reduce redundant constraints are for avoidance of all the calculations associated when solving an associated linear programming problems. Many researchers have been proposed for identification redundant constraints. This paper a compararison of Heuristic method and Llewellyn’s rules for identification of redundant constraints.

  16. Uncontrolled Manifold Reference Feedback Control of Multi-Joint Robot Arms

    PubMed Central

    Togo, Shunta; Kagawa, Takahiro; Uno, Yoji

    2016-01-01

    The brain must coordinate with redundant bodies to perform motion tasks. The aim of the present study is to propose a novel control model that predicts the characteristics of human joint coordination at a behavioral level. To evaluate the joint coordination, an uncontrolled manifold (UCM) analysis that focuses on the trial-to-trial variance of joints has been proposed. The UCM is a nonlinear manifold associated with redundant kinematics. In this study, we directly applied the notion of the UCM to our proposed control model called the “UCM reference feedback control.” To simplify the problem, the present study considered how the redundant joints were controlled to regulate a given target hand position. We considered a conventional method that pre-determined a unique target joint trajectory by inverse kinematics or any other optimization method. In contrast, our proposed control method generates a UCM as a control target at each time step. The target UCM is a subspace of joint angles whose variability does not affect the hand position. The joint combination in the target UCM is then selected so as to minimize the cost function, which consisted of the joint torque and torque change. To examine whether the proposed method could reproduce human-like joint coordination, we conducted simulation and measurement experiments. In the simulation experiments, a three-link arm with a shoulder, elbow, and wrist regulates a one-dimensional target of a hand through proposed method. In the measurement experiments, subjects performed a one-dimensional target-tracking task. The kinematics, dynamics, and joint coordination were quantitatively compared with the simulation data of the proposed method. As a result, the UCM reference feedback control could quantitatively reproduce the difference of the mean value for the end hand position between the initial postures, the peaks of the bell-shape tangential hand velocity, the sum of the squared torque, the mean value for the torque change, the variance components, and the index of synergy as well as the human subjects. We concluded that UCM reference feedback control can reproduce human-like joint coordination. The inference for motor control of the human central nervous system based on the proposed method was discussed. PMID:27462215

  17. Digital flight control actuation system study

    NASA Technical Reports Server (NTRS)

    Rossing, R.; Hupp, R.

    1974-01-01

    Flight control actuators and feedback sensors suitable for use in a redundant digital flight control system were examined. The most appropriate design approach for an advanced digital flight control actuation system for development and use in a fly-by-wire system was selected. The concept which was selected consisted of a PM torque motor direct drive. The selected system is compatible with concurrent and independent development efforts on the computer system and the control law mechanizations.

  18. A software architecture for hard real-time execution of automatically synthesized plans or control laws

    NASA Technical Reports Server (NTRS)

    Schoppers, Marcel

    1994-01-01

    The design of a flexible, real-time software architecture for trajectory planning and automatic control of redundant manipulators is described. Emphasis is placed on a technique of designing control systems that are both flexible and robust yet have good real-time performance. The solution presented involves an artificial intelligence algorithm that dynamically reprograms the real-time control system while planning system behavior.

  19. The 747 primary flight control systems reliability and maintenance study

    NASA Technical Reports Server (NTRS)

    1979-01-01

    The major operational characteristics of the 747 Primary Flight Control Systems (PFCS) are described. Results of reliability analysis for separate control functions are presented. The analysis makes use of a NASA computer program which calculates reliability of redundant systems. Costs for maintaining the 747 PFCS in airline service are assessed. The reliabilities and cost will provide a baseline for use in trade studies of future flight control system design.

  20. Dual redundant core memory systems

    NASA Technical Reports Server (NTRS)

    Hull, F. E.

    1972-01-01

    Electronic memory system consisting of series redundant drive switch circuits, triple redundant majority voted memory timing functions, and two data registers to provide functional dual redundancy is described. Signal flow through the circuits is illustrated and equence of events which occur within the memory system is explained.

  1. Two inwardly rectifying potassium channels, Irk1 and Irk2, play redundant roles in Drosophila renal tubule function

    PubMed Central

    Wu, Yipin; Baum, Michel; Huang, Chou-Long

    2015-01-01

    Inwardly rectifying potassium channels play essential roles in renal physiology across phyla. Barium-sensitive K+ conductances are found on the basolateral membrane of a variety of insect Malpighian (renal) tubules, including Drosophila melanogaster. We found that barium decreases the lumen-positive transepithelial potential difference in isolated perfused Drosophila tubules and decreases fluid secretion and transepithelial K+ flux. In those insect species in which it has been studied, transcripts from multiple genes encoding inwardly rectifying K+ channels are expressed in the renal (Malpighian) tubule. In Drosophila melanogaster, this includes transcripts of the Irk1, Irk2, and Irk3 genes. The role of each of these gene products in renal tubule function is unknown. We found that simultaneous knockdown of Irk1 and Irk2 in the principal cell of the fly tubule decreases transepithelial K+ flux, with no additive effect of Irk3 knockdown, and decreases barium sensitivity of transepithelial K+ flux by ∼50%. Knockdown of any of the three inwardly rectifying K+ channels individually has no effect, nor does knocking down Irk3 simultaneously with Irk1 or Irk2. Irk1/Irk2 principal cell double-knockdown tubules remain sensitive to the kaliuretic effect of cAMP. Inhibition of the Na+/K+-ATPase with ouabain and Irk1/Irk2 double knockdown have additive effects on K+ flux, and 75% of transepithelial K+ transport is due to Irk1/Irk2 or ouabain-sensitive pathways. In conclusion, Irk1 and Irk2 play redundant roles in transepithelial ion transport in the Drosophila melanogaster renal tubule and are additive to Na+/K+-ATPase-dependent pathways. PMID:26224687

  2. BMP, Wnt and FGF signals are integrated through evolutionarily conserved enhancers to achieve robust expression of Pax3 and Zic genes at the zebrafish neural plate border

    PubMed Central

    Garnett, Aaron T.; Square, Tyler A.; Medeiros, Daniel M.

    2012-01-01

    Neural crest cells generate a range of cells and tissues in the vertebrate head and trunk, including peripheral neurons, pigment cells, and cartilage. Neural crest cells arise from the edges of the nascent central nervous system, a domain called the neural plate border (NPB). NPB induction is known to involve the BMP, Wnt and FGF signaling pathways. However, little is known about how these signals are integrated to achieve temporally and spatially specific expression of genes in NPB cells. Furthermore, the timing and relative importance of these signals in NPB formation appears to differ between vertebrate species. Here, we use heat-shock overexpression and chemical inhibitors to determine whether, and when, BMP, Wnt and FGF signaling are needed for expression of the NPB specifiers pax3a and zic3 in zebrafish. We then identify four evolutionarily conserved enhancers from the pax3a and zic3 loci and test their response to BMP, Wnt and FGF perturbations. We find that all three signaling pathways are required during gastrulation for the proper expression of pax3a and zic3 in the zebrafish NPB. We also find that, although the expression patterns driven by the pax3a and zic3 enhancers largely overlap, they respond to different combinations of BMP, Wnt and FGF signals. Finally, we show that the combination of the two pax3a enhancers is less susceptible to signaling perturbations than either enhancer alone. Taken together, our results reveal how BMPs, FGFs and Wnts act cooperatively and redundantly through partially redundant enhancers to achieve robust, specific gene expression in the zebrafish NPB. PMID:23034628

  3. Adaptive Nonlinear Tracking Control of Kinematically Redundant Robot Manipulators with Sub-Task Extensions

    DTIC Science & Technology

    2005-01-01

    C. Hughes, Spacecraft Attitude Dynamics, New York, NY: Wiley, 1994. [8] H. K. Khalil, “Adaptive Output Feedback Control of Non- linear Systems...Closed-Loop Manipulator Control Using Quaternion Feedback ”, IEEE Trans. Robotics and Automation, Vol. 4, No. 4, pp. 434-440, (1988). [23] E...full-state feedback quaternion based controller de- veloped in [5] and focuses on the design of a general sub-task controller. This sub-task controller

  4. The Effects of Race Conditions when Implementing Single-Source Redundant Clock Trees in Triple Modular Redundant Synchronous Architectures

    NASA Technical Reports Server (NTRS)

    Berg, Melanie D.; Label, Kenneth A.; Pellish, Jonathan

    2016-01-01

    We present the challenges that arise when using redundant clock domains due to their clock-skew. Heavy-ion radiation data show that a singular clock domain (DTMR) provides an improved TMR methodology for SRAM-based FPGAs over redundant clocks.

  5. Intersensory Redundancy Enhances Memory in Bobwhite Quail Embryos

    ERIC Educational Resources Information Center

    Lickliter, Robert; Bahrick, Lorraine E.; Honeycutt, Hunter

    2004-01-01

    Information presented concurrently and redundantly to 2 or more senses (intersensory redundancy) has been shown to recruit attention and promote perceptual learning of amodal stimulus properties in animal embryos and human infants. This study examined whether the facilitative effect of intersensory redundancy also extends to the domain of memory.…

  6. Fusion Prevents the Redundant Signals Effect: Evidence from Stereoscopically Presented Stimuli

    ERIC Educational Resources Information Center

    Schroter, Hannes; Fiedler, Anja; Miller, Jeff; Ulrich, Rolf

    2011-01-01

    In a simple reaction time (RT) experiment, visual stimuli were stereoscopically presented either to one eye (single stimulation) or to both eyes (redundant stimulation), with brightness matched for single and redundant stimulations. Redundant stimulation resulted in two separate percepts when noncorresponding retinal areas were stimulated, whereas…

  7. LEGO: a novel method for gene set over-representation analysis by incorporating network-based gene weights

    PubMed Central

    Dong, Xinran; Hao, Yun; Wang, Xiao; Tian, Weidong

    2016-01-01

    Pathway or gene set over-representation analysis (ORA) has become a routine task in functional genomics studies. However, currently widely used ORA tools employ statistical methods such as Fisher’s exact test that reduce a pathway into a list of genes, ignoring the constitutive functional non-equivalent roles of genes and the complex gene-gene interactions. Here, we develop a novel method named LEGO (functional Link Enrichment of Gene Ontology or gene sets) that takes into consideration these two types of information by incorporating network-based gene weights in ORA analysis. In three benchmarks, LEGO achieves better performance than Fisher and three other network-based methods. To further evaluate LEGO’s usefulness, we compare LEGO with five gene expression-based and three pathway topology-based methods using a benchmark of 34 disease gene expression datasets compiled by a recent publication, and show that LEGO is among the top-ranked methods in terms of both sensitivity and prioritization for detecting target KEGG pathways. In addition, we develop a cluster-and-filter approach to reduce the redundancy among the enriched gene sets, making the results more interpretable to biologists. Finally, we apply LEGO to two lists of autism genes, and identify relevant gene sets to autism that could not be found by Fisher. PMID:26750448

  8. LEGO: a novel method for gene set over-representation analysis by incorporating network-based gene weights.

    PubMed

    Dong, Xinran; Hao, Yun; Wang, Xiao; Tian, Weidong

    2016-01-11

    Pathway or gene set over-representation analysis (ORA) has become a routine task in functional genomics studies. However, currently widely used ORA tools employ statistical methods such as Fisher's exact test that reduce a pathway into a list of genes, ignoring the constitutive functional non-equivalent roles of genes and the complex gene-gene interactions. Here, we develop a novel method named LEGO (functional Link Enrichment of Gene Ontology or gene sets) that takes into consideration these two types of information by incorporating network-based gene weights in ORA analysis. In three benchmarks, LEGO achieves better performance than Fisher and three other network-based methods. To further evaluate LEGO's usefulness, we compare LEGO with five gene expression-based and three pathway topology-based methods using a benchmark of 34 disease gene expression datasets compiled by a recent publication, and show that LEGO is among the top-ranked methods in terms of both sensitivity and prioritization for detecting target KEGG pathways. In addition, we develop a cluster-and-filter approach to reduce the redundancy among the enriched gene sets, making the results more interpretable to biologists. Finally, we apply LEGO to two lists of autism genes, and identify relevant gene sets to autism that could not be found by Fisher.

  9. Use of graphics in decision aids for telerobotic control: (Parts 5-8 of an 8-part MIT progress report)

    NASA Technical Reports Server (NTRS)

    Sheridan, Thomas B.; Roseborough, James B.; Das, Hari; Chin, Kan-Ping; Inoue, Seiichi

    1989-01-01

    Four separate projects recently completed or in progress at the MIT Man-Machine Systems Laboratory are summarized. They are: a decision aid for retrieving a tumbling satellite in space; kinematic control and graphic display of redundant teleoperators; real time terrain/object generation: a quad-tree approach; and two dimensional control for three dimensional obstacle avoidance.

  10. Interface For Fault-Tolerant Control System

    NASA Technical Reports Server (NTRS)

    Shaver, Charles; Williamson, Michael

    1989-01-01

    Interface unit and controller emulator developed for research on electronic helicopter-flight-control systems equipped with artificial intelligence. Interface unit interrupt-driven system designed to link microprocessor-based, quadruply-redundant, asynchronous, ultra-reliable, fault-tolerant control system (controller) with electronic servocontrol unit that controls set of hydraulic actuators. Receives digital feedforward messages from, and transmits digital feedback messages to, controller through differential signal lines or fiber-optic cables (thus far only differential signal lines have been used). Analog signals transmitted to and from servocontrol unit via coaxial cables.

  11. Experiments in structural dynamics and control using a grid

    NASA Technical Reports Server (NTRS)

    Montgomery, R. C.

    1985-01-01

    Future spacecraft are being conceived that are highly flexible and of extreme size. The two features of flexibility and size pose new problems in control system design. Since large scale structures are not testable in ground based facilities, the decision on component placement must be made prior to full-scale tests on the spacecraft. Control law research is directed at solving problems of inadequate modelling knowledge prior to operation required to achieve peak performance. Another crucial problem addressed is accommodating failures in systems with smart components that are physically distributed on highly flexible structures. Parameter adaptive control is a method of promise that provides on-orbit tuning of the control system to improve performance by upgrading the mathematical model of the spacecraft during operation. Two specific questions are answered in this work. They are: What limits does on-line parameter identification with realistic sensors and actuators place on the ultimate achievable performance of a system in the highly flexible environment? Also, how well must the mathematical model used in on-board analytic redundancy be known and what are the reasonable expectations for advanced redundancy management schemes in the highly flexible and distributed component environment?

  12. The Inertial Upper Stage - Flight experience and capabilities

    NASA Astrophysics Data System (ADS)

    Kuhns, Randall H.; Maricich, Peter L.; Bangsund, Edward L.; Friske, Stephen A.; Hallman, Wayne P.; Goldstein, Allen E.

    1993-10-01

    The Inertial Upper Stage (IUS) is a two-stage rocket designed to place a variety of payloads in high earth orbit or on interplanetary trajectories, which has been boosted to date, together with its payloads, from the earth's surface to low altitude park orbits by the USAF Titan launcher and the NASA Space Shuttle. This paper discusses the IUS redundancy and presents data on the value of the IST's redundant design and the past uses of the vehicle's redundant capability to achieve mission success. The value of IUS's redundancy has been confirmed on several flights. The paper presents block diagrams of the IUS redundancy architecture and of the redundancy hardware switching and commands.

  13. Equifinality and its violations in a redundant system: multifinger accurate force production

    PubMed Central

    Wilhelm, Luke; Zatsiorsky, Vladimir M.

    2013-01-01

    We explored a hypothesis that transient perturbations applied to a redundant system result in equifinality in the space of task-related performance variables but not in the space of elemental variables. The subjects pressed with four fingers and produced an accurate constant total force level. The “inverse piano” device was used to lift and lower one of the fingers smoothly. The subjects were instructed “not to intervene voluntarily” with possible force changes. Analysis was performed in spaces of finger forces and finger modes (hypothetical neural commands to fingers) as elemental variables. Lifting a finger led to an increase in its force and a decrease in the forces of the other three fingers; the total force increased. Lowering the finger back led to a drop in the force of the perturbed finger. At the final state, the sum of the variances of finger forces/modes computed across repetitive trials was significantly higher than the variance of the total force/mode. Most variance of the individual finger force/mode changes between the preperturbation and postperturbation states was compatible with constant total force. We conclude that a transient perturbation applied to a redundant system leads to relatively small variance in the task-related performance variable (equifinality), whereas in the space of elemental variables much more variance occurs that does not lead to total force changes. We interpret the results within a general theoretical scheme that incorporates the ideas of hierarchically organized control, control with referent configurations, synergic control, and the uncontrolled manifold hypothesis. PMID:23904497

  14. Multiple cytoskeletal pathways and PI3K signaling mediate CDC-42-induced neuronal protrusion in C. elegans.

    PubMed

    Alan, Jamie K; Struckhoff, Eric C; Lundquist, Erik A

    2013-01-01

    Rho GTPases are key regulators of cellular protrusion and are involved in many developmental events including axon guidance during nervous system development. Rho GTPase pathways display functional redundancy in developmental events, including axon guidance. Therefore, their roles can often be masked when using simple loss-of-function genetic approaches. As a complement to loss-of-function genetics, we constructed a constitutively activated CDC-42(G12V) expressed in C. elegans neurons. CDC-42(G12V) drove the formation of ectopic lamellipodial and filopodial protrusions in the PDE neurons, which resembled protrusions normally found on migrating growth cones of axons. We then used a candidate gene approach to identify molecules that mediate CDC-42(G12V)-induced ectopic protrusions by determining if loss of function of the genes could suppress CDC-42(G12V). Using this approach, we identified 3 cytoskeletal pathways previously implicated in axon guidance, the Arp2/3 complex, UNC-115/abLIM, and UNC-43/Ena. We also identified the Nck-interacting kinase MIG-15/NIK and p21-activated kinases (PAKs), also implicated in axon guidance. Finally, PI3K signaling was required, specifically the Rictor/mTORC2 branch but not the mTORC1 branch that has been implicated in other aspects of PI3K signaling including stress and aging. Our results indicate that multiple pathways can mediate CDC-42-induced neuronal protrusions that might be relevant to growth cone protrusions during axon pathfinding. Each of these pathways involves Rac GTPases, which might serve to integrate the pathways and coordinate the multiple CDC-42 pathways. These pathways might be relevant to developmental events such as axon pathfinding as well as disease states such as metastatic melanoma.

  15. Multiple cytoskeletal pathways and PI3K signaling mediate CDC-42-induced neuronal protrusion in C. elegans

    PubMed Central

    Alan, Jamie K; Struckhoff, Eric C; Lundquist, Erik A

    2013-01-01

    Rho GTPases are key regulators of cellular protrusion and are involved in many developmental events including axon guidance during nervous system development. Rho GTPase pathways display functional redundancy in developmental events, including axon guidance. Therefore, their roles can often be masked when using simple loss-of-function genetic approaches. As a complement to loss-of-function genetics, we constructed a constitutively activated CDC-42(G12V) expressed in C. elegans neurons. CDC-42(G12V) drove the formation of ectopic lamellipodial and filopodial protrusions in the PDE neurons, which resembled protrusions normally found on migrating growth cones of axons. We then used a candidate gene approach to identify molecules that mediate CDC-42(G12V)-induced ectopic protrusions by determining if loss of function of the genes could suppress CDC-42(G12V). Using this approach, we identified 3 cytoskeletal pathways previously implicated in axon guidance, the Arp2/3 complex, UNC-115/abLIM, and UNC-43/Ena. We also identified the Nck-interacting kinase MIG-15/NIK and p21-activated kinases (PAKs), also implicated in axon guidance. Finally, PI3K signaling was required, specifically the Rictor/mTORC2 branch but not the mTORC1 branch that has been implicated in other aspects of PI3K signaling including stress and aging. Our results indicate that multiple pathways can mediate CDC-42-induced neuronal protrusions that might be relevant to growth cone protrusions during axon pathfinding. Each of these pathways involves Rac GTPases, which might serve to integrate the pathways and coordinate the multiple CDC-42 pathways. These pathways might be relevant to developmental events such as axon pathfinding as well as disease states such as metastatic melanoma. PMID:24149939

  16. Commensurate distances and similar motifs in genetic congruence and protein interaction networks in yeast

    PubMed Central

    Ye, Ping; Peyser, Brian D; Spencer, Forrest A; Bader, Joel S

    2005-01-01

    Background In a genetic interaction, the phenotype of a double mutant differs from the combined phenotypes of the underlying single mutants. When the single mutants have no growth defect, but the double mutant is lethal or exhibits slow growth, the interaction is termed synthetic lethality or synthetic fitness. These genetic interactions reveal gene redundancy and compensating pathways. Recently available large-scale data sets of genetic interactions and protein interactions in Saccharomyces cerevisiae provide a unique opportunity to elucidate the topological structure of biological pathways and how genes function in these pathways. Results We have defined congruent genes as pairs of genes with similar sets of genetic interaction partners and constructed a genetic congruence network by linking congruent genes. By comparing path lengths in three types of networks (genetic interaction, genetic congruence, and protein interaction), we discovered that high genetic congruence not only exhibits correlation with direct protein interaction linkage but also exhibits commensurate distance with the protein interaction network. However, consistent distances were not observed between genetic and protein interaction networks. We also demonstrated that congruence and protein networks are enriched with motifs that indicate network transitivity, while the genetic network has both transitive (triangle) and intransitive (square) types of motifs. These results suggest that robustness of yeast cells to gene deletions is due in part to two complementary pathways (square motif) or three complementary pathways, any two of which are required for viability (triangle motif). Conclusion Genetic congruence is superior to genetic interaction in prediction of protein interactions and function associations. Genetically interacting pairs usually belong to parallel compensatory pathways, which can generate transitive motifs (any two of three pathways needed) or intransitive motifs (either of two pathways needed). PMID:16283923

  17. The effect of a redundant color code on an overlearned identification task

    NASA Technical Reports Server (NTRS)

    Obrien, Kevin

    1992-01-01

    The possibility of finding redundancy gains with overlearned tasks was examined using a paradigm varying familiarity with the stimulus set. Redundant coding in a multidimensional stimulus was demonstrated to result in increased identification accuracy and decreased latency of identification when compared to stimuli varying on only one dimension. The advantages attributable to redundant coding are referred to as redundancy gain and were found for a variety of stimulus dimension combinations, including the use of hue or color as one of the dimensions. Factors that have affected redundancy gain include the discriminability of the levels of one stimulus dimension and the level of stimulus-to-response association. The results demonstrated that response time is in part a function of familiarity, but no effect of redundant color coding was demonstrated. Implications of research on coding in identification tasks for display design are discussed.

  18. System For Research On Multiple-Arm Robots

    NASA Technical Reports Server (NTRS)

    Backes, Paul G.; Hayati, Samad; Tso, Kam S.; Hayward, Vincent

    1991-01-01

    Kali system of computer programs and equipment provides environment for research on distributed programming and distributed control of coordinated-multiple-arm robots. Suitable for telerobotics research involving sensing and execution of low level tasks. Software and configuration of hardware designed flexible so system modified easily to test various concepts in control and programming of robots, including multiple-arm control, redundant-arm control, shared control, traded control, force control, force/position hybrid control, design and integration of sensors, teleoperation, task-space description and control, methods of adaptive control, control of flexible arms, and human factors.

  19. Introducing "biophysical redundancy": the global status and past evolution of unused water, land and productivity resources for food production

    NASA Astrophysics Data System (ADS)

    Fader, Marianela

    2017-04-01

    Countries have different resilience to sudden and long-term changes in food demand and supply. An important part of this resilience is the degree of biophysical redundancy, defined as the potential food production of 'spare land', available water resources (i.e., not already used for human activities), as well as production increases through yield gap closure on cultivated areas and potential agricultural areas. The presentation will show the results of a recently published paper1 on the evolution of biophysical redundancy for agricultural production at country level, from 1992 to 2012. Results indicate that in 2012, the biophysical redundancy of 75 (48) countries, mainly in North Africa, Western Europe, the Middle East and Asia, was insufficient to produce the caloric nutritional needs for at least 50% (25%) of their population during a year. Biophysical redundancy has decreased in the last two decades in 102 out of 155 countries, 11 of these went from high to limited redundancy, and nine of these from limited to very low redundancy. Although the variability of the drivers of change across different countries is high, improvements in yield and population growth have a clear impact on the decreases of redundancy towards the very low redundancy category. We took a more detailed look at countries classified as 'Low Income Economies (LIEs)' since they are particularly vulnerable to domestic or external food supply changes, due to their limited capacity to offset for food supply decreases with higher purchasing power on the international market. Currently, nine LIEs have limited or very low biophysical redundancy. Many of these showed a decrease in redundancy over the last two decades, which is not always linked with improvements in per capita food availability.

  20. Past and Present Biophysical Redundancy of Countries as a Buffer to Changes in Food Supply

    NASA Technical Reports Server (NTRS)

    Fader, Marianela; Rulli, Maria Cristina; Carr, Joel; Dell' Angelo, Jampel; D' Odorico, Paolo; Gephart, Jessica A.; Kummu, Matti; Magliocca, Nicholas; Porkka, Miina; Prell, Christina; hide

    2016-01-01

    Spatially diverse trends in population growth, climate change, industrialization, urbanization and economic development are expected to change future food supply and demand. These changes may affect the suitability of land for food production, implying elevated risks especially for resource constrained, food-importing countries. We present the evolution of biophysical redundancy for agricultural production at country level, from 1992 to 2012. Biophysical redundancy, defined as unused biotic and abiotic environmental resources, is represented by the potential food production of 'spare land', available water resources (i.e., not already used for human activities), as well as production increases through yield gap closure on cultivated areas and potential agricultural areas. In 2012, the biophysical redundancy of 75 (48) countries, mainly in North Africa, Western Europe, the Middle East and Asia, was insufficient to produce the caloric nutritional needs for at least 50% (25%) of their population during a year. Biophysical redundancy has decreased in the last two decades in 102 out of 155 countries, 11 of these went from high to limited redundancy, and nine of these from limited to very low redundancy. Although the variability of the drivers of change across different countries is high, improvements in yield and population growth have a clear impact on the decreases of redundancy towards the very low redundancy category. We took a more detailed look at countries classified as 'Low Income Economies (LIEs)' since they are particularly vulnerable to domestic or external food supply changes, due to their limited capacity to offset for food supply decreases with higher purchasing power on the international market. Currently, nine LIEs have limited or very low biophysical redundancy. Many of these showed a decrease in redundancy over the last two decades, which is not always linked with improvements in per capita food availability.

  1. Superconducting Coil Winding Machine Control System

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

    Nogiec, J. M.; Kotelnikov, S.; Makulski, A.

    The Spirex coil winding machine is used at Fermilab to build coils for superconducting magnets. Recently this ma-chine was equipped with a new control system, which al-lows operation from both a computer and a portable remote control unit. This control system is distributed between three layers, implemented on a PC, real-time target, and FPGA, providing respectively HMI, operational logic and direct controls. The system controls motion of all mechan-ical components and regulates the cable tension. Safety is ensured by a failsafe, redundant system.

  2. Advanced information processing system

    NASA Technical Reports Server (NTRS)

    Lala, J. H.

    1984-01-01

    Design and performance details of the advanced information processing system (AIPS) for fault and damage tolerant data processing on aircraft and spacecraft are presented. AIPS comprises several computers distributed throughout the vehicle and linked by a damage tolerant data bus. Most I/O functions are available to all the computers, which run in a TDMA mode. Each computer performs separate specific tasks in normal operation and assumes other tasks in degraded modes. Redundant software assures that all fault monitoring, logging and reporting are automated, together with control functions. Redundant duplex links and damage-spread limitation provide the fault tolerance. Details of an advanced design of a laboratory-scale proof-of-concept system are described, including functional operations.

  3. Basic multisensory functions can be acquired after congenital visual pattern deprivation in humans.

    PubMed

    Putzar, Lisa; Gondan, Matthias; Röder, Brigitte

    2012-01-01

    People treated for bilateral congenital cataracts offer a model to study the influence of visual deprivation in early infancy on visual and multisensory development. We investigated cross-modal integration capabilities in cataract patients using a simple detection task that provided redundant information to two different senses. In both patients and controls, redundancy gains were consistent with coactivation models, indicating an integrated processing of modality-specific information. This finding is in contrast with recent studies showing impaired higher-level multisensory interactions in cataract patients. The present results suggest that basic cross-modal integrative processes for simple short stimuli do not depend on visual and/or crossmodal input since birth.

  4. Chemical genomics in plant biology.

    PubMed

    Sadhukhan, Ayan; Sahoo, Lingaraj; Panda, Sanjib Kumar

    2012-06-01

    Chemical genomics is a newly emerged and rapidly progressing field in biology, where small chemical molecules bind specifically and reversibly to protein(s) to modulate their function(s), leading to the delineation and subsequent unravelling of biological processes. This approach overcomes problems like lethality and redundancy of classical genetics. Armed with the powerful techniques of combinatorial synthesis, high-throughput screening and target discovery chemical genomics expands its scope to diverse areas in biology. The well-established genetic system of Arabidopsis model allows chemical genomics to enter into the realm of plant biology exploring signaling pathways of growth regulators, endomembrane signaling cascades, plant defense mechanisms and many more events.

  5. Proteome insights into the symbiotic relationship between a captive colony of Nasutitermes corniger and its hindgut microbiome

    PubMed Central

    Burnum, Kristin E; Callister, Stephen J; Nicora, Carrie D; Purvine, Samuel O; Hugenholtz, Philip; Warnecke, Falk; Scheffrahn, Rudolf H; Smith, Richard D; Lipton, Mary S

    2011-01-01

    We analyzed the metaproteome of the bacterial community resident in the hindgut paunch of the wood-feeding ‘higher' termite (Nasutitermes) and identified 886 proteins, 197 of which have known enzymatic function. Using these enzymes, we reconstructed complete metabolic pathways revealing carbohydrate transport and metabolism, nitrogen fixation and assimilation, energy production, amino-acid synthesis and significant pyruvate ferredoxin/flavodoxin oxidoreductase protein redundancy. Our results suggest that the activity associated with these enzymes may have more of a role in the symbiotic relationship between the hindgut microbial community and its termite host than activities related to cellulose degradation. PMID:20613792

  6. [Current Topics on Vitamin D. The vitamin D functions in keratinocytes and its therapeutic applications].

    PubMed

    Sawatsubashi, Shun

    2015-03-01

    1,25 (OH) 2D and calcium have been shown to promote epidermal keratinocyte differentiation and prevent proliferation. These prodifferentiation and antiproliferative effects of 1,25 (OH) 2D have led to its clinical use in the treatment of psoriasis. However, the mechanism of vitamin D action on keratinocytes remains largely unknown. While the actions of calcium and the vitamin D receptor signaling pathways on epidermal keratinocyte differentiation are redundant, their effects on the hair follicle are not. In this review, we discuss how the vitamin D and its receptor contribute to skin and hair follicle homeostasis.

  7. Imaging metabolic heterogeneity in cancer.

    PubMed

    Sengupta, Debanti; Pratx, Guillem

    2016-01-06

    As our knowledge of cancer metabolism has increased, it has become apparent that cancer metabolic processes are extremely heterogeneous. The reasons behind this heterogeneity include genetic diversity, the existence of multiple and redundant metabolic pathways, altered microenvironmental conditions, and so on. As a result, methods in the clinic and beyond have been developed in order to image and study tumor metabolism in the in vivo and in vitro regimes. Both regimes provide unique advantages and challenges, and may be used to provide a picture of tumor metabolic heterogeneity that is spatially and temporally comprehensive. Taken together, these methods may hold the key to appropriate cancer diagnoses and treatments in the future.

  8. Methods for increasing noise immunity of radio electronic systems with redundancy

    NASA Astrophysics Data System (ADS)

    Orlov, P. E.; Medvedev, A. V.; Sharafutdinov, V. R.; Gazizov, T. R.; Ubaichin, A. V.

    2018-05-01

    The idea of increasing the noise immunity of radioelectronic systems with redundancy is presented. Specific technical solutions based on this idea of modal redundancy are described. An estimation of noise immunity improvement was performed by the example of implementation of modal redundancy with the broad-side electromagnetic coupling for a printed circuit board of the digital signal processing unit for an autonomous navigation system of a spacecraft. It is shown that the implementation of modal redundancy can provide an attenuation coefficient for the interference signal up to 12 dB.

  9. Study of techniques for redundancy verification without disrupting systems, phases 1-3

    NASA Technical Reports Server (NTRS)

    1970-01-01

    The problem of verifying the operational integrity of redundant equipment and the impact of a requirement for verification on such equipment are considered. Redundant circuits are examined and the characteristics which determine adaptability to verification are identified. Mutually exclusive and exhaustive categories for verification approaches are established. The range of applicability of these techniques is defined in terms of signal characteristics and redundancy features. Verification approaches are discussed and a methodology for the design of redundancy verification is developed. A case study is presented which involves the design of a verification system for a hypothetical communications system. Design criteria for redundant equipment are presented. Recommendations for the development of technological areas pertinent to the goal of increased verification capabilities are given.

  10. Cryptic biodiversity effects: importance of functional redundancy revealed through addition of food web complexity.

    PubMed

    Philpott, Stacy M; Pardee, Gabriella L; Gonthier, David J

    2012-05-01

    Interactions between predators and the degree of functional redundancy among multiple predator species may determine whether herbivores experience increased or decreased predation risk. Specialist parasites can modify predator behavior, yet rarely have cascading effects on multiple predator species and prey been evaluated. We examined influences of specialist phorid parasites (Pseudacteon spp.) on three predatory ant species and herbivores in a coffee agroecosystem. Specifically, we examined whether changes in ant richness affected fruit damage by the coffee berry borer (Hypothenemus hampei) and whether phorids altered multi-predator effects. Each ant species reduced borer damage, and without phorids, increasing predator richness did not further decrease borer damage. However, with phorids, activity of one ant species was reduced, indicating that the presence of multiple ant species was necessary to limit borer damage. In addition, phorid presence revealed synergistic effects of multiple ant species, not observed without the presence of this parasite. Thus, a trait-mediated cascade resulting from a parasite-induced predator behavioral change revealed the importance of functional redundancy, predator diversity, and food web complexity for control of this important pest.

  11. High precision redundant robotic manipulator

    DOEpatents

    Young, K.K.D.

    1998-09-22

    A high precision redundant robotic manipulator for overcoming contents imposed by obstacles or imposed by a highly congested work space is disclosed. One embodiment of the manipulator has four degrees of freedom and another embodiment has seven degrees of freedom. Each of the embodiments utilize a first selective compliant assembly robot arm (SCARA) configuration to provide high stiffness in the vertical plane, a second SCARA configuration to provide high stiffness in the horizontal plane. The seven degree of freedom embodiment also utilizes kinematic redundancy to provide the capability of avoiding obstacles that lie between the base of the manipulator and the end effector or link of the manipulator. These additional three degrees of freedom are added at the wrist link of the manipulator to provide pitch, yaw and roll. The seven degrees of freedom embodiment uses one revolute point per degree of freedom. For each of the revolute joints, a harmonic gear coupled to an electric motor is introduced, and together with properly designed based servo controllers provide an end point repeatability of less than 10 microns. 3 figs.

  12. Development of 3000 m Subsea Blowout Preventer Experimental Prototype

    NASA Astrophysics Data System (ADS)

    Cai, Baoping; Liu, Yonghong; Huang, Zhiqian; Ma, Yunpeng; Zhao, Yubin

    2017-12-01

    A subsea blowout preventer experimental prototype is developed to meet the requirement of training operators, and the prototype consists of hydraulic control system, electronic control system and small-sized blowout preventer stack. Both the hydraulic control system and the electronic system are dual-mode redundant systems. Each system works independently and is switchable when there are any malfunctions. And it significantly improves the operation reliability of the equipment.

  13. The F-12 series aircraft approach to design for control system reliability

    NASA Technical Reports Server (NTRS)

    Schenk, F. L.; Mcmaster, J. R.

    1976-01-01

    The F-12 series aircraft control system design philosophy is reviewed as it pertains to functional reliability. The basic control system, i.e., cables, mixer, feel system, trim devices, and hydraulic systems are described and discussed. In addition, the implementation of the redundant stability augmentation system in the F-12 aircraft is described. Finally, the functional reliability record that has been achieved is presented.

  14. Multi-finger prehension: control of a redundant mechanical system.

    PubMed

    Latash, Mark L; Zatsiorsky, Vladimir M

    2009-01-01

    The human hand has been a fascinating object of study for researchers in both biomechanics and motor control. Studies of human prehension have contributed significantly to the progress in addressing the famous problem of motor redundancy. After a brief review of the hand mechanics, we present results of recent studies that support a general view that the apparently redundant design of the hand is not a source of computational problems but a rich apparatus that allows performing a variety of tasks in a reliable and flexible way (the principle of abundance). Multi-digit synergies have been analyzed at two levels of a hypothetical hierarchy involved in the control of prehensile actions. At the upper level, forces and moments produced by the thumb and virtual finger (an imagined finger with a mechanical action equal to the combined mechanical action of all four fingers of the hand) co-vary to stabilize the gripping action and the orientation of the hand-held object. These results support the principle of superposition suggested earlier in robotics with respect to the control of artificial grippers. At the lower level of the hierarchy, forces and moments produced by individual fingers co-vary to stabilize the magnitude and direction of the force vector and the moment of force produced by the virtual finger. Adjustments to changes in task constraints (such as, for example, friction under individual digits) may be local and synergic. The latter reflect multi-digit prehension synergies and may be analyzed with the so-called chain effects: Sequences of relatively straightforward cause-effect links directly related to mechanical constraints leading to non-trivial strong co-variation between pairs of elemental variables. Analysis of grip force adjustments during motion of hand-held objects suggests that the central nervous system adjusts to gravitational and inertial loads differently. The human hand is a gold mine for researchers interested in the control of natural human movements.

  15. Influence of the Redundant Verification and the Non-Redundant Verification on the Hydraulic Tomography

    NASA Astrophysics Data System (ADS)

    Wei, T. B.; Chen, Y. L.; Lin, H. R.; Huang, S. Y.; Yeh, T. C. J.; Wen, J. C.

    2016-12-01

    In the groundwater study, it estimated the heterogeneous spatial distribution of hydraulic Properties, there were many scholars use to hydraulic tomography (HT) from field site pumping tests to estimate inverse of heterogeneous spatial distribution of hydraulic Properties, to prove the most of most field site aquifer was heterogeneous hydrogeological parameters spatial distribution field. Many scholars had proposed a method of hydraulic tomography to estimate heterogeneous spatial distribution of hydraulic Properties of aquifer, the Huang et al. [2011] was used the non-redundant verification analysis of pumping wells changed, observation wells fixed on the inverse and the forward, to reflect the feasibility of the heterogeneous spatial distribution of hydraulic Properties of field site aquifer of the non-redundant verification analysis on steady-state model.From post literature, finding only in steady state, non-redundant verification analysis of pumping well changed location and observation wells fixed location for inverse and forward. But the studies had not yet pumping wells fixed or changed location, and observation wells fixed location for redundant verification or observation wells change location for non-redundant verification of the various combinations may to explore of influences of hydraulic tomography method. In this study, it carried out redundant verification method and non-redundant verification method for forward to influences of hydraulic tomography method in transient. And it discuss above mentioned in NYUST campus sites the actual case, to prove the effectiveness of hydraulic tomography methods, and confirmed the feasibility on inverse and forward analysis from analysis results.Keywords: Hydraulic Tomography, Redundant Verification, Heterogeneous, Inverse, Forward

  16. Redundant Design in Interdependent Networks

    PubMed Central

    2016-01-01

    Modern infrastructure networks are often coupled together and thus could be modeled as interdependent networks. Overload and interdependent effect make interdependent networks more fragile when suffering from attacks. Existing research has primarily concentrated on the cascading failure process of interdependent networks without load, or the robustness of isolated network with load. Only limited research has been done on the cascading failure process caused by overload in interdependent networks. Redundant design is a primary approach to enhance the reliability and robustness of the system. In this paper, we propose two redundant methods, node back-up and dependency redundancy, and the experiment results indicate that two measures are effective and costless. Two detailed models about redundant design are introduced based on the non-linear load-capacity model. Based on the attributes and historical failure distribution of nodes, we introduce three static selecting strategies-Random-based, Degree-based, Initial load-based and a dynamic strategy-HFD (historical failure distribution) to identify which nodes could have a back-up with priority. In addition, we consider the cost and efficiency of different redundant proportions to determine the best proportion with maximal enhancement and minimal cost. Experiments on interdependent networks demonstrate that the combination of HFD and dependency redundancy is an effective and preferred measure to implement redundant design on interdependent networks. The results suggest that the redundant design proposed in this paper can permit construction of highly robust interactive networked systems. PMID:27764174

  17. Effects of Response Task and Accessory Stimuli on Redundancy Gain: Tests of the Hemispheric Coactivation Model

    ERIC Educational Resources Information Center

    Miller, Jeff; Van Nes, Fenna

    2007-01-01

    Two experiments tested predictions of the hemispheric coactivation model for redundancy gain (J. O. Miller, 2004). Simple reaction time was measured in divided attention tasks with visual stimuli presented to the left or right of fixation or redundantly to both sides. Experiment 1 tested the prediction that redundancy gain--the decrease in…

  18. Guidance and control/ACEE

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Active controls improve airplane performance by stabilizing its flight, reducing departures from stable flight, and alleviating loads imposed by external forces such as gusts, turbulence, or maneuvers. Some uses for active control systems, the design of redundant and reliable stability augmentation systems, digital fly-by-wire, and NASA assessments of the technology of sensors and actuators are discussed. A series of trade-off studies to better define optimum flight control systems, and research by drone and full-scale models are described.

  19. AGARD Flight Test Instrumentation Series. Volume 14. The Analysis of Random Data

    DTIC Science & Technology

    1981-11-01

    obtained at arbitrary times during a number of flights. No constraints have been placed upon the controlling parameters, so that the process is non ...34noisy" environment controlling a non -linear system (the aircraft) using a redundant net of control parameters. when aircraft were flown manually with...structure. Cuse 2. Non -Stationary Measurements. When the 114S value of a random signal varies with parameters which cannot be controlled , then the method

  20. Human Prostate Cancer Hallmarks Map

    PubMed Central

    Datta, Dipamoy; Aftabuddin, Md.; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

    2016-01-01

    Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process. PMID:27476486

  1. Tracing the Repertoire of Promiscuous Enzymes along the Metabolic Pathways in Archaeal Organisms.

    PubMed

    Martínez-Núñez, Mario Alberto; Rodríguez-Escamilla, Zuemy; Rodríguez-Vázquez, Katya; Pérez-Rueda, Ernesto

    2017-07-13

    The metabolic pathways that carry out the biochemical transformations sustaining life depend on the efficiency of their associated enzymes. In recent years, it has become clear that promiscuous enzymes have played an important role in the function and evolution of metabolism. In this work we analyze the repertoire of promiscuous enzymes in 89 non-redundant genomes of the Archaea cellular domain. Promiscuous enzymes are defined as those proteins with two or more different Enzyme Commission (E.C.) numbers, according the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. From this analysis, it was found that the fraction of promiscuous enzymes is lower in Archaea than in Bacteria. A greater diversity of superfamily domains is associated with promiscuous enzymes compared to specialized enzymes, both in Archaea and Bacteria, and there is an enrichment of substrate promiscuity rather than catalytic promiscuity in the archaeal enzymes. Finally, the presence of promiscuous enzymes in the metabolic pathways was found to be heterogeneously distributed at the domain level and in the phyla that make up the Archaea. These analyses increase our understanding of promiscuous enzymes and provide additional clues to the evolution of metabolism in Archaea.

  2. Combined loss of three DNA damage response pathways renders C. elegans intolerant to light.

    PubMed

    van Bostelen, Ivo; Tijsterman, Marcel

    2017-06-01

    Infliction of DNA damage initiates a complex cellular reaction - the DNA damage response - that involves both signaling and DNA repair networks with many redundancies and parallel pathways. Here, we reveal the three strategies that the simple multicellular eukaryote, C. elegans, uses to deal with DNA damage induced by light. Separately inactivating repair or replicative bypass of photo-lesions results in cellular hypersensitivity towards UV-light, but impeding repair of replication associated DNA breaks does not. Yet, we observe an unprecedented synergistic relationship when these pathways are inactivated in combination. C. elegans mutants that lack nucleotide excision repair (NER), translesion synthesis (TLS) and alternative end joining (altEJ) grow undisturbed in the dark, but become sterile when grown in light. Even exposure to very low levels of normal daylight impedes animal growth. We show that NER and TLS operate to suppress the formation of lethal DNA breaks that require polymerase theta-mediated end joining (TMEJ) for their repair. Our data testifies to the enormous genotoxicity of light and to the demand of multiple layers of protection against an environmental threat that is so common. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Androgen biosynthesis in castration-resistant prostate cancer

    PubMed Central

    Penning, Trevor M

    2014-01-01

    Prostate cancer is the second leading cause of death in adult males in the USA. Recent advances have revealed that the fatal form of this cancer, known as castration-resistant prostate cancer (CRPC), remains hormonally driven despite castrate levels of circulating androgens. CRPC arises as the tumor undergoes adaptation to low levels of androgens by either synthesizing its own androgens (intratumoral androgens) or altering the androgen receptor (AR). This article reviews the major routes to testosterone and dihydrotestosterone synthesis in CRPC cells and examines the enzyme targets and progress in the development of isoform-specific inhibitors that could block intratumoral androgen biosynthesis. Because redundancy exists in these pathways, it is likely that inhibition of a single pathway will lead to upregulation of another so that drug resistance would be anticipated. Drugs that target multiple pathways or bifunctional agents that block intratumoral androgen biosynthesis and antagonize the AR offer the most promise. Optimal use of enzyme inhibitors or AR antagonists to ensure maximal benefits to CRPC patients will also require application of precision molecular medicine to determine whether a tumor in a particular patient will be responsive to these treatments either alone or in combination. PMID:24829267

  4. Frequency encoded auditory display of the critical tracking task

    NASA Technical Reports Server (NTRS)

    Stevenson, J.

    1984-01-01

    The use of auditory displays for selected cockpit instruments was examined. In auditory, visual, and combined auditory-visual compensatory displays of a vertical axis, critical tracking task were studied. The visual display encoded vertical error as the position of a dot on a 17.78 cm, center marked CRT. The auditory display encoded vertical error as log frequency with a six octave range; the center point at 1 kHz was marked by a 20-dB amplitude notch, one-third octave wide. Asymptotic performance on the critical tracking task was significantly better when using combined displays rather than the visual only mode. At asymptote, the combined display was slightly, but significantly, better than the visual only mode. The maximum controllable bandwidth using the auditory mode was only 60% of the maximum controllable bandwidth using the visual mode. Redundant cueing increased the rate of improvement of tracking performance, and the asymptotic performance level. This enhancement increases with the amount of redundant cueing used. This effect appears most prominent when the bandwidth of the forcing function is substantially less than the upper limit of controllability frequency.

  5. A unified motion planning approach for redundant and non-redundant manipulators with actuator constraints. Ph.D. Thesis Final Report

    NASA Technical Reports Server (NTRS)

    Chung, Ching-Luan

    1990-01-01

    The term trajectory planning has been used to refer to the process of determining the time history of joint trajectory of each joint variable corresponding to a specified trajectory of the end effector. The trajectory planning problem was solved as a purely kinematic problem. The drawback is that there is no guarantee that the actuators can deliver the effort necessary to track the planned trajectory. To overcome this limitation, a motion planning approach which addresses the kinematics, dynamics, and feedback control of a manipulator in a unified framework was developed. Actuator constraints are taken into account explicitly and a priori in the synthesis of the feedback control law. Therefore the result of applying the motion planning approach described is not only the determination of the entire set of joint trajectories but also a complete specification of the feedback control strategy which would yield these joint trajectories without violating actuator constraints. The effectiveness of the unified motion planning approach is demonstrated on two problems which are of practical interest in manipulator robotics.

  6. Redundant operation of counter modules

    NASA Technical Reports Server (NTRS)

    Nagano, S. (Inventor)

    1980-01-01

    A technique for the redundant operation of counter modules is described. Redundant operation is maintained by detecting the zero state of each counter and clearing the other to that state, thus periodically resynchronizing the counters, and obtaining an output from both counters through AC coupled diode-OR gates. Redundant operation of counter flip flops is maintained in a similar manner, and synchronous operation of redundant squarewave clock generators of the feedback type is effected by connecting together the feedback inputs of the squarewave generators through a coupling resistor, and obtaining an output from both generators through AC coupled diode-OR gates.

  7. Phosphoketolase pathway contributes to carbon metabolism in cyanobacteria.

    PubMed

    Xiong, Wei; Lee, Tai-Chi; Rommelfanger, Sarah; Gjersing, Erica; Cano, Melissa; Maness, Pin-Ching; Ghirardi, Maria; Yu, Jianping

    2015-12-07

    Central carbon metabolism in cyanobacteria comprises the Calvin-Benson-Bassham (CBB) cycle, glycolysis, the pentose phosphate (PP) pathway and the tricarboxylic acid (TCA) cycle. Redundancy in this complex metabolic network renders the rational engineering of cyanobacterial metabolism for the generation of biomass, biofuels and chemicals a challenge. Here we report the presence of a functional phosphoketolase pathway, which splits xylulose-5-phosphate (or fructose-6-phosphate) to acetate precursor acetyl phosphate, in an engineered strain of the model cyanobacterium Synechocystis (ΔglgC/xylAB), in which glycogen synthesis is blocked, and xylose catabolism enabled through the introduction of xylose isomerase and xylulokinase. We show that this mutant strain is able to metabolise xylose to acetate on nitrogen starvation. To see whether acetate production in the mutant is linked to the activity of phosphoketolase, we disrupted a putative phosphoketolase gene (slr0453) in the ΔglgC/xylAB strain, and monitored metabolic flux using (13)C labelling; acetate and 2-oxoglutarate production was reduced in the light. A metabolic flux analysis, based on isotopic data, suggests that the phosphoketolase pathway metabolises over 30% of the carbon consumed by ΔglgC/xylAB during photomixotrophic growth on xylose and CO2. Disruption of the putative phosphoketolase gene in wild-type Synechocystis also led to a deficiency in acetate production in the dark, indicative of a contribution of the phosphoketolase pathway to heterotrophic metabolism. We suggest that the phosphoketolase pathway, previously uncharacterized in photosynthetic organisms, confers flexibility in energy and carbon metabolism in cyanobacteria, and could be exploited to increase the efficiency of cyanobacterial carbon metabolism and photosynthetic productivity.

  8. In silico evolution of the hunchback gene indicates redundancy in cis-regulatory organization and spatial gene expression

    PubMed Central

    Zagrijchuk, Elizaveta A.; Sabirov, Marat A.; Holloway, David M.; Spirov, Alexander V.

    2014-01-01

    Biological development depends on the coordinated expression of genes in time and space. Developmental genes have extensive cis-regulatory regions which control their expression. These regions are organized in a modular manner, with different modules controlling expression at different times and locations. Both how modularity evolved and what function it serves are open questions. We present a computational model for the cis-regulation of the hunchback (hb) gene in the fruit fly (Drosophila). We simulate evolution (using an evolutionary computation approach from computer science) to find the optimal cis-regulatory arrangements for fitting experimental hb expression patterns. We find that the cis-regulatory region tends to readily evolve modularity. These cis-regulatory modules (CRMs) do not tend to control single spatial domains, but show a multi-CRM/multi-domain correspondence. We find that the CRM-domain correspondence seen in Drosophila evolves with a high probability in our model, supporting the biological relevance of the approach. The partial redundancy resulting from multi-CRM control may confer some biological robustness against corruption of regulatory sequences. The technique developed on hb could readily be applied to other multi-CRM developmental genes. PMID:24712536

  9. Restoring Redundancy to the Wilkinson Microwave Anisotrophy Probe Propulsion System

    NASA Technical Reports Server (NTRS)

    O'Donnell, James R., Jr.; Davis, Gary T.; Ward, David K.

    2004-01-01

    The Wilkinson Microwave Anisotropy Probe is a follow-on to the Differential Microwave Radiometer instrument on the Cosmic Background Explorer. Attitude control system engineers discovered sixteen months before launch that configuration changes after the critical design review had resulted in a significant migration of the spacecraft's center of mass. As a result, the spacecraft no longer had a viable backup control mode in the event of a failure of the negative pitch-axis thruster. A tiger team was formed and identified potential solutions to this problem, such as adding thruster-plume shields to redirect thruster torque, adding or removing mass from the spacecraft, adding an additional thruster, moving thrusters, bending thruster nozzles or propellant tubing, or accepting the loss of redundancy. The project considered the impacts on mass, cost, fuel budget, and schedule for each solution, and decided to bend the propellant tubing of the two roll-control thrusters to allow the pair to be used for backup control in the negative pitch axis. This paper discusses the problem and the potential solutions, and documents the hardware and software changes and verification performed. Flight data are presented to show the on-orbit performance of the propulsion system and lessons learned are described.

  10. A manipulative instrument with simultaneous gesture and end-effector trajectory planning and controlling

    NASA Astrophysics Data System (ADS)

    Lin, Hsien-I.; Nguyen, Xuan-Anh

    2017-05-01

    To operate a redundant manipulator to accomplish the end-effector trajectory planning and simultaneously control its gesture in online programming, incorporating the human motion is a useful and flexible option. This paper focuses on a manipulative instrument that can simultaneously control its arm gesture and end-effector trajectory via human teleoperation. The instrument can be classified by two parts; first, for the human motion capture and data processing, marker systems are proposed to capture human gesture. Second, the manipulator kinematics control is implemented by an augmented multi-tasking method, and forward and backward reaching inverse kinematics, respectively. Especially, the local-solution and divergence problems of a multi-tasking method are resolved by the proposed augmented multi-tasking method. Computer simulations and experiments with a 7-DOF (degree of freedom) redundant manipulator were used to validate the proposed method. Comparison among the single-tasking, original multi-tasking, and augmented multi-tasking algorithms were performed and the result showed that the proposed augmented method had a good end-effector position accuracy and the most similar gesture to the human gesture. Additionally, the experimental results showed that the proposed instrument was realized online.

  11. Entropy-Based Bounds On Redundancies Of Huffman Codes

    NASA Technical Reports Server (NTRS)

    Smyth, Padhraic J.

    1992-01-01

    Report presents extension of theory of redundancy of binary prefix code of Huffman type which includes derivation of variety of bounds expressed in terms of entropy of source and size of alphabet. Recent developments yielded bounds on redundancy of Huffman code in terms of probabilities of various components in source alphabet. In practice, redundancies of optimal prefix codes often closer to 0 than to 1.

  12. Saccharomyces cerevisiae KTR4, KTR5 and KTR7 encode mannosyltransferases differentially involved in the N- and O-linked glycosylation pathways.

    PubMed

    Hernández, Nahúm V; López-Ramírez, Luz A; Díaz-Jiménez, Diana F; Mellado-Mojica, Erika; Martínez-Duncker, Iván; López, Mercedes G; Mora-Montes, Héctor M

    2017-10-01

    Saccharomyces cerevisiae is a model to understand basic aspects of protein glycosylation pathways. Although these metabolic routes have been thoroughly studied, there are still knowledge gaps; among them, the role of the MNT1/KRE2 gene family. This family is composed of nine members, with only six functionally characterized. The enzymes Ktr1, Ktr3, and Mnt1/Kre2 have overlapping activities in both O-linked and N-linked glycan synthesis; while Ktr2 and Yur1 participate exclusively in the elongation of the N-linked glycan outer chain. KTR6 encodes for a phosphomannosyltransferase that synthesizes the cell wall phosphomannan. Here, we aimed to establish the functional role of KTR4, KTR5 and KTR7 in the protein glycosylation pathways, by using heterologous complementation in Candida albicans null mutants lacking members of the MNT1/KRE2 gene family. The three S. cerevisiae genes restored defects in the C. albicans N-linked glycosylation pathway. KTR5 and KTR7 partially complemented a C. albicans null mutant with defects in the synthesis of O-linked glycans, and only KTR4 fully elongated the O-linked glycans like wild-type cells. Therefore, our results suggest that the three genes have a redundant activity in the S. cerevisiae N-linked glycosylation pathway, but KTR4 plays a major role in O-linked glycan synthesis. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  13. DNA Repair Mechanisms and the Bypass of DNA Damage in Saccharomyces cerevisiae

    PubMed Central

    Boiteux, Serge; Jinks-Robertson, Sue

    2013-01-01

    DNA repair mechanisms are critical for maintaining the integrity of genomic DNA, and their loss is associated with cancer predisposition syndromes. Studies in Saccharomyces cerevisiae have played a central role in elucidating the highly conserved mechanisms that promote eukaryotic genome stability. This review will focus on repair mechanisms that involve excision of a single strand from duplex DNA with the intact, complementary strand serving as a template to fill the resulting gap. These mechanisms are of two general types: those that remove damage from DNA and those that repair errors made during DNA synthesis. The major DNA-damage repair pathways are base excision repair and nucleotide excision repair, which, in the most simple terms, are distinguished by the extent of single-strand DNA removed together with the lesion. Mistakes made by DNA polymerases are corrected by the mismatch repair pathway, which also corrects mismatches generated when single strands of non-identical duplexes are exchanged during homologous recombination. In addition to the true repair pathways, the postreplication repair pathway allows lesions or structural aberrations that block replicative DNA polymerases to be tolerated. There are two bypass mechanisms: an error-free mechanism that involves a switch to an undamaged template for synthesis past the lesion and an error-prone mechanism that utilizes specialized translesion synthesis DNA polymerases to directly synthesize DNA across the lesion. A high level of functional redundancy exists among the pathways that deal with lesions, which minimizes the detrimental effects of endogenous and exogenous DNA damage. PMID:23547164

  14. Metabolic Network for the Biosynthesis of Intra- and Extracellular α-Glucans Required for Virulence of Mycobacterium tuberculosis

    PubMed Central

    van de Weerd, Robert; Chandra, Govind; Appelmelk, Ben; Alber, Marina; Ioerger, Thomas R.; Jacobs, William R.; Geurtsen, Jeroen; Bornemann, Stephen

    2016-01-01

    Mycobacterium tuberculosis synthesizes intra- and extracellular α-glucans that were believed to originate from separate pathways. The extracellular glucose polymer is the main constituent of the mycobacterial capsule that is thought to be involved in immune evasion and virulence. However, the role of the α-glucan capsule in pathogenesis has remained enigmatic due to an incomplete understanding of α-glucan biosynthetic pathways preventing the generation of capsule-deficient mutants. Three separate and potentially redundant pathways had been implicated in α-glucan biosynthesis in mycobacteria: the GlgC-GlgA, the Rv3032 and the TreS-Pep2-GlgE pathways. We now show that α-glucan in mycobacteria is exclusively assembled intracellularly utilizing the building block α-maltose-1-phosphate as the substrate for the maltosyltransferase GlgE, with subsequent branching of the polymer by the branching enzyme GlgB. Some α-glucan is exported to form the α-glucan capsule. There is an unexpected convergence of the TreS-Pep2 and GlgC-GlgA pathways that both generate α-maltose-1-phosphate. While the TreS-Pep2 route from trehalose was already known, we have now established that GlgA forms this phosphosugar from ADP-glucose and glucose 1-phosphate 1000-fold more efficiently than its hitherto described glycogen synthase activity. The two routes are connected by the common precursor ADP-glucose, allowing compensatory flux from one route to the other. Having elucidated this unexpected configuration of the metabolic pathways underlying α-glucan biosynthesis in mycobacteria, an M. tuberculosis double mutant devoid of α-glucan could be constructed, showing a direct link between the GlgE pathway, α-glucan biosynthesis and virulence in a mouse infection model. PMID:27513637

  15. Past and present biophysical redundancy of countries as a buffer to changes in food supply

    NASA Astrophysics Data System (ADS)

    Fader, Marianela; Rulli, Maria Cristina; Carr, Joel; Dell'Angelo, Jampel; D'Odorico, Paolo; Gephart, Jessica A.; Kummu, Matti; Magliocca, Nicholas; Porkka, Miina; Prell, Christina; Puma, Michael J.; Ratajczak, Zak; Seekell, David A.; Suweis, Samir; Tavoni, Alessandro

    2016-05-01

    Spatially diverse trends in population growth, climate change, industrialization, urbanization and economic development are expected to change future food supply and demand. These changes may affect the suitability of land for food production, implying elevated risks especially for resource-constrained, food-importing countries. We present the evolution of biophysical redundancy for agricultural production at country level, from 1992 to 2012. Biophysical redundancy, defined as unused biotic and abiotic environmental resources, is represented by the potential food production of ‘spare land’, available water resources (i.e., not already used for human activities), as well as production increases through yield gap closure on cultivated areas and potential agricultural areas. In 2012, the biophysical redundancy of 75 (48) countries, mainly in North Africa, Western Europe, the Middle East and Asia, was insufficient to produce the caloric nutritional needs for at least 50% (25%) of their population during a year. Biophysical redundancy has decreased in the last two decades in 102 out of 155 countries, 11 of these went from high to limited redundancy, and nine of these from limited to very low redundancy. Although the variability of the drivers of change across different countries is high, improvements in yield and population growth have a clear impact on the decreases of redundancy towards the very low redundancy category. We took a more detailed look at countries classified as ‘Low Income Economies (LIEs)’ since they are particularly vulnerable to domestic or external food supply changes, due to their limited capacity to offset for food supply decreases with higher purchasing power on the international market. Currently, nine LIEs have limited or very low biophysical redundancy. Many of these showed a decrease in redundancy over the last two decades, which is not always linked with improvements in per capita food availability.

  16. Quantifying electrical impacts on redundant wire insertion in 7nm unidirectional designs

    NASA Astrophysics Data System (ADS)

    Mohyeldin, Ahmed; Schroeder, Uwe Paul; Srinivasan, Ramya; Narisetty, Haritez; Malik, Shobhit; Madhavan, Sriram

    2017-04-01

    In nano-meter scale Integrated Circuits, via fails due to random defects is a well-known yield detractor, and via redundancy insertion is a common method to help enhance semiconductors yield. For the case of Self Aligned Double Patterning (SADP), which might require unidirectional design layers as in the case of some advanced technology nodes, the conventional methods of inserting redundant vias don't work any longer. This is because adding redundant vias conventionally requires adding metal shapes in the non-preferred direction, which will violate the SADP design constraints in that case. Therefore, such metal layers fabricated using unidirectional SADP require an alternative method for providing the needed redundancy. This paper proposes a post-layout Design for Manufacturability (DFM) redundancy insertion method tailored for the design requirements introduced by unidirectional metal layers. The proposed method adds redundant wires in the preferred direction - after searching for nearby vacant routing tracks - in order to provide redundant paths for electrical signals. This method opportunistically adds robustness against failures due to silicon defects without impacting area or incurring new design rule violations. Implementation details of this redundancy insertion method will be explained in this paper. One known challenge with similar DFM layout fixing methods is the possible introduction of undesired electrical impact, causing other unintentional failures in design functionality. In this paper, a study is presented to quantify the electrical impacts of such redundancy insertion scheme and to examine if that electrical impact can be tolerated. The paper will show results to evaluate DFM insertion rates and corresponding electrical impact for a given design utilization and maximum inserted wire length. Parasitic extraction and static timing analysis results will be presented. A typical digital design implemented using GLOBALFOUNDRIES 7nm technology is used for demonstration. The provided results can help evaluate such extensive DFM insertion method from an electrical standpoint. Furthermore, the results could provide guidance on how to implement the proposed method of adding electrical redundancy such that intolerable electrical impacts could be avoided.

  17. Detecting clinically relevant new information in clinical notes across specialties and settings.

    PubMed

    Zhang, Rui; Pakhomov, Serguei V S; Arsoniadis, Elliot G; Lee, Janet T; Wang, Yan; Melton, Genevieve B

    2017-07-05

    Automated methods for identifying clinically relevant new versus redundant information in electronic health record (EHR) clinical notes is useful for clinicians and researchers involved in patient care and clinical research, respectively. We evaluated methods to automatically identify clinically relevant new information in clinical notes, and compared the quantity of redundant information across specialties and clinical settings. Statistical language models augmented with semantic similarity measures were evaluated as a means to detect and quantify clinically relevant new and redundant information over longitudinal clinical notes for a given patient. A corpus of 591 progress notes over 40 inpatient admissions was annotated for new information longitudinally by physicians to generate a reference standard. Note redundancy between various specialties was evaluated on 71,021 outpatient notes and 64,695 inpatient notes from 500 solid organ transplant patients (April 2015 through August 2015). Our best method achieved at best performance of 0.87 recall, 0.62 precision, and 0.72 F-measure. Addition of semantic similarity metrics compared to baseline improved recall but otherwise resulted in similar performance. While outpatient and inpatient notes had relatively similar levels of high redundancy (61% and 68%, respectively), redundancy differed by author specialty with mean redundancy of 75%, 66%, 57%, and 55% observed in pediatric, internal medicine, psychiatry and surgical notes, respectively. Automated techniques with statistical language models for detecting redundant versus clinically relevant new information in clinical notes do not improve with the addition of semantic similarity measures. While levels of redundancy seem relatively similar in the inpatient and ambulatory settings in the Fairview Health Services, clinical note redundancy appears to vary significantly with different medical specialties.

  18. Signaling pathways regulating the expression of Prx1 and Prx2 in the Chick Mandibular Mesenchyme

    PubMed Central

    Doufexi, Aikaterini-El; Mina, Mina

    2009-01-01

    Prx1 and Prx2 are members of the aristaless-related homeobox genes shown to play redundant but essential roles in morphogenesis of the mandibular processes. To gain insight into the signaling pathways that regulate expression of Prx genes in the mandibular mesenchyme, we used the chick as a model system. We examined the patterns of gene expression in the face and the roles of signals derived from the epithelium on the expression of Prx genes in the mandibular mesenchyme. Our results demonstrated stage-dependent roles of mandibular epithelium on the expression of Prx in the mandibular mesenchyme and provide evidence for positive roles of members of the fibroblast and hedgehog families derived from mandibular epithelium on the expression of Prx genes in the mandibular mesenchyme. Our studies suggest that endothelin-1 signaling derived from the mesenchyme is involved in restricting the expression of Prx2 to the medial mandibular mesenchyme. PMID:18942149

  19. Femara® and the future: tailoring treatment and combination therapies with Femara

    PubMed Central

    Ma, Cynthia

    2007-01-01

    Long-term estrogen deprivation treatment for breast cancer can, in some patients, lead to the activation of alternate cellular pathways, resulting in the re-emergence of the disease. This is a distressing scenario for oncologists and patients, but recent intensive molecular and biochemical studies are beginning to unravel these pathways, revealing opportunities for new targeted treatments. Far from making present therapies redundant, these new discoveries open the door to novel combination therapies that promise to provide enhanced efficacy or overcome treatment resistance. Letrozole, one of the most potent aromatase inhibitors, is the ideal candidate for combination therapy; indeed, it is one of the most intensively studied aromatase inhibitors in the evolving combinatorial setting. Complementary to the use of combination therapy is the development of molecular tools to identify patients who will benefit the most from these new treatments. Microarray gene profiling studies, designed to detect letrozole-responsive targets, are currently under way to understand how the use of the drug can be tailored more efficiently to specific patient needs. PMID:17912640

  20. Functions of Adaptor Protein (AP)-3 and AP-1 in Tyrosinase Sorting from Endosomes to MelanosomesD⃞

    PubMed Central

    Theos, Alexander C.; Tenza, Danièle; Martina, José A.; Hurbain, Ilse; Peden, Andrew A.; Sviderskaya, Elena V.; Stewart, Abigail; Robinson, Margaret S.; Bennett, Dorothy C.; Cutler, Daniel F.; Bonifacino, Juan S.; Marks, Michael S.; Raposo, Graça

    2005-01-01

    Specialized cells exploit adaptor protein complexes for unique post-Golgi sorting events, providing a unique model system to specify adaptor function. Here, we show that AP-3 and AP-1 function independently in sorting of the melanocyte-specific protein tyrosinase from endosomes to the melanosome, a specialized lysosome-related organelle distinguishable from lysosomes. AP-3 and AP-1 localize in melanocytes primarily to clathrin-coated buds on tubular early endosomes near melanosomes. Both adaptors recognize the tyrosinase dileucine-based melanosome sorting signal, and tyrosinase largely colocalizes with each adaptor on endosomes. In AP-3-deficient melanocytes, tyrosinase accumulates inappropriately in vacuolar and multivesicular endosomes. Nevertheless, a substantial fraction still accumulates on melanosomes, concomitant with increased association with endosomal AP-1. Our data indicate that AP-3 and AP-1 function in partially redundant pathways to transfer tyrosinase from distinct endosomal subdomains to melanosomes and that the AP-3 pathway ensures that tyrosinase averts entrapment on internal membranes of forming multivesicular bodies. PMID:16162817

  1. Redundant interferometric calibration as a complex optimization problem

    NASA Astrophysics Data System (ADS)

    Grobler, T. L.; Bernardi, G.; Kenyon, J. S.; Parsons, A. R.; Smirnov, O. M.

    2018-05-01

    Observations of the redshifted 21 cm line from the epoch of reionization have recently motivated the construction of low-frequency radio arrays with highly redundant configurations. These configurations provide an alternative calibration strategy - `redundant calibration' - and boost sensitivity on specific spatial scales. In this paper, we formulate calibration of redundant interferometric arrays as a complex optimization problem. We solve this optimization problem via the Levenberg-Marquardt algorithm. This calibration approach is more robust to initial conditions than current algorithms and, by leveraging an approximate matrix inversion, allows for further optimization and an efficient implementation (`redundant STEFCAL'). We also investigated using the preconditioned conjugate gradient method as an alternative to the approximate matrix inverse, but found that its computational performance is not competitive with respect to `redundant STEFCAL'. The efficient implementation of this new algorithm is made publicly available.

  2. Fault Detection and Isolation for Hydraulic Control

    NASA Technical Reports Server (NTRS)

    1987-01-01

    Pressure sensors and isolation valves act to shut down defective servochannel. Redundant hydraulic system indirectly senses failure in any of its electrical control channels and mechanically isolates hydraulic channel controlled by faulty electrical channel so flat it cannot participate in operating system. With failure-detection and isolation technique, system can sustains two failed channels and still functions at full performance levels. Scheme useful on aircraft or other systems with hydraulic servovalves where failure cannot be tolerated.

  3. On the design of fault-tolerant robotic manipulator systems

    NASA Technical Reports Server (NTRS)

    Tesar, Delbert

    1993-01-01

    Robotic systems are finding increasing use in space applications. Many of these devices are going to be operational on board the Space Station Freedom. Fault tolerance has been deemed necessary because of the criticality of the tasks and the inaccessibility of the systems to maintenance and repair. Design for fault tolerance in manipulator systems is an area within robotics that is without precedence in the literature. In this paper, we will attempt to lay down the foundations for such a technology. Design for fault tolerance demands new and special approaches to design, often at considerable variance from established design practices. These design aspects, together with reliability evaluation and modeling tools, are presented. Mechanical architectures that employ protective redundancies at many levels and have a modular architecture are then studied in detail. Once a mechanical architecture for fault tolerance has been derived, the chronological stages of operational fault tolerance are investigated. Failure detection, isolation, and estimation methods are surveyed, and such methods for robot sensors and actuators are derived. Failure recovery methods are also presented for each of the protective layers of redundancy. Failure recovery tactics often span all of the layers of a control hierarchy. Thus, a unified framework for decision-making and control, which orchestrates both the nominal redundancy management tasks and the failure management tasks, has been derived. The well-developed field of fault-tolerant computers is studied next, and some design principles relevant to the design of fault-tolerant robot controllers are abstracted. Conclusions are drawn, and a road map for the design of fault-tolerant manipulator systems is laid out with recommendations for a 10 DOF arm with dual actuators at each joint.

  4. Preliminary design of a redundant strapped down inertial navigation unit using two-degree-of-freedom tuned-gimbal gyroscopes

    NASA Technical Reports Server (NTRS)

    1976-01-01

    This redundant strapdown INS preliminary design study demonstrates the practicality of a skewed sensor system configuration by means of: (1) devising a practical system mechanization utilizing proven strapdown instruments, (2) thoroughly analyzing the skewed sensor redundancy management concept to determine optimum geometry, data processing requirements, and realistic reliability estimates, and (3) implementing the redundant computers into a low-cost, maintainable configuration.

  5. The role of redundant information in cultural transmission and cultural stabilization.

    PubMed

    Acerbi, Alberto; Tennie, Claudio

    2016-02-01

    Redundant copying has been proposed as a manner to achieve the high-fidelity necessary to pass on and preserve complex traits in human cultural transmission. There are at least 2 ways to define redundant copying. One refers to the possibility of copying repeatedly the same trait over time, and another to the ability to exploit multiple layers of information pointing to the same trait during a single copying event. Using an individual-based model, we explore how redundant copying (defined as in the latter way) helps to achieve successful transmission. The authors show that increasing redundant copying increases the likelihood of accurately transmitting a behavior more than either augmenting the number of copying occasions across time or boosting the general accuracy of social learning. They also investigate how different cost functions, deriving, for example, from the need to invest more energy in cognitive processing, impact the evolution of redundant copying. The authors show that populations converge either to high-fitness/high-costs states (with high redundant copying and complex culturally transmitted behaviors; resembling human culture) or to low-fitness/low-costs states (with low redundant copying and simple transmitted behaviors; resembling social learning forms typical of nonhuman animals). This outcome may help to explain why cumulative culture is rare in the animal kingdom. (c) 2016 APA, all rights reserved).

  6. A robust H∞-tracking design for uncertain Takagi-Sugeno fuzzy systems with unknown premise variables using descriptor redundancy approach

    NASA Astrophysics Data System (ADS)

    Hassan Asemani, Mohammad; Johari Majd, Vahid

    2015-12-01

    This paper addresses a robust H∞ fuzzy observer-based tracking design problem for uncertain Takagi-Sugeno fuzzy systems with external disturbances. To have a practical observer-based controller, the premise variables of the system are assumed to be not measurable in general, which leads to a more complex design process. The tracker is synthesised based on a fuzzy Lyapunov function approach and non-parallel distributed compensation (non-PDC) scheme. Using the descriptor redundancy approach, the robust stability conditions are derived in the form of strict linear matrix inequalities (LMIs) even in the presence of uncertainties in the system, input, and output matrices simultaneously. Numerical simulations are provided to show the effectiveness of the proposed method.

  7. Redundancy management of multiple KT-70 inertial measurement units applicable to the space shuttle

    NASA Technical Reports Server (NTRS)

    Cook, L. J.

    1975-01-01

    Results of an investigation of velocity failure detection and isolation for 3 inertial measuring units (IMU) and 2 inertial measuring units (IMU) configurations are presented. The failure detection and isolation algorithm performance was highly successful and most types of velocity errors were detected and isolated. The failure detection and isolation algorithm also included attitude FDI but was not evaluated because of the lack of time and low resolution in the gimbal angle synchro outputs. The shuttle KT-70 IMUs will have dual-speed resolvers and high resolution gimbal angle readouts. It was demonstrated by these tests that a single computer utilizing a serial data bus can successfully control a redundant 3-IMU system and perform FDI.

  8. Analytical sensor redundancy assessment

    NASA Technical Reports Server (NTRS)

    Mulcare, D. B.; Downing, L. E.; Smith, M. K.

    1988-01-01

    The rationale and mechanization of sensor fault tolerance based on analytical redundancy principles are described. The concept involves the substitution of software procedures, such as an observer algorithm, to supplant additional hardware components. The observer synthesizes values of sensor states in lieu of their direct measurement. Such information can then be used, for example, to determine which of two disagreeing sensors is more correct, thus enhancing sensor fault survivability. Here a stability augmentation system is used as an example application, with required modifications being made to a quadruplex digital flight control system. The impact on software structure and the resultant revalidation effort are illustrated as well. Also, the use of an observer algorithm for wind gust filtering of the angle-of-attack sensor signal is presented.

  9. An atypical bHLH protein encoded by POSITIVE REGULATOR OF GRAIN LENGTH 2 is involved in controlling grain length and weight of rice through interaction with a typical bHLH protein APG.

    PubMed

    Heang, Dany; Sassa, Hidenori

    2012-06-01

    Grain size is an important yield component in rice, however, genes controlling the trait remain poorly understood. Previously, we have shown that an antagonistic pair of basic helix-loop-helix (bHLH) proteins, POSITIVE REGULATOR OF GRAIN LENGTH 1 (PGL1) and ANTAGONIST OF PGL1 (APG), is involved in controlling rice grain length. Here, we report the involvement of another atypical bHLH protein gene, POSITIVE REGULATOR OF GRAIN LENGTH 2 (PGL2), in the regulation of rice grain length. Over-expression of PGL2 in the lemma/palea increased grain length and weight in correlation with the level of transgene expression. Observation of the inner epidermal cells of lemma of PGL2-overexpressing lines revealed that the long grain size is caused by an increase in cell length. PGL2 interacts with a typical bHLH protein APG, a negative regulator of rice grain length and weight, in vitro and in vivo. It was reported that overexpression of BU1 (BRASSINOSTEROID UPREGULATED 1), the closest homolog of PGL2, caused an increase in grain length. However, we detected no interaction between BU1 and APG. These findings suggest that PGL2 and PGL1 redundantly suppress the function of APG by forming heterodimers to positively regulate the rice grain length, while the pathway through which BU1, the closest homolog of PGL2, controls grain length is independent of APG.

  10. An atypical bHLH protein encoded by POSITIVE REGULATOR OF GRAIN LENGTH 2 is involved in controlling grain length and weight of rice through interaction with a typical bHLH protein APG

    PubMed Central

    Heang, Dany; Sassa, Hidenori

    2012-01-01

    Grain size is an important yield component in rice, however, genes controlling the trait remain poorly understood. Previously, we have shown that an antagonistic pair of basic helix-loop-helix (bHLH) proteins, POSITIVE REGULATOR OF GRAIN LENGTH 1 (PGL1) and ANTAGONIST OF PGL1 (APG), is involved in controlling rice grain length. Here, we report the involvement of another atypical bHLH protein gene, POSITIVE REGULATOR OF GRAIN LENGTH 2 (PGL2), in the regulation of rice grain length. Over-expression of PGL2 in the lemma/palea increased grain length and weight in correlation with the level of transgene expression. Observation of the inner epidermal cells of lemma of PGL2-overexpressing lines revealed that the long grain size is caused by an increase in cell length. PGL2 interacts with a typical bHLH protein APG, a negative regulator of rice grain length and weight, in vitro and in vivo. It was reported that overexpression of BU1 (BRASSINOSTEROID UPREGULATED 1), the closest homolog of PGL2, caused an increase in grain length. However, we detected no interaction between BU1 and APG. These findings suggest that PGL2 and PGL1 redundantly suppress the function of APG by forming heterodimers to positively regulate the rice grain length, while the pathway through which BU1, the closest homolog of PGL2, controls grain length is independent of APG. PMID:23136524

  11. Cardiac neuronal hierarchy in health and disease.

    PubMed

    Armour, J Andrew

    2004-08-01

    The cardiac neuronal hierarchy can be represented as a redundant control system made up of spatially distributed cell stations comprising afferent, efferent, and interconnecting neurons. Its peripheral and central neurons are in constant communication with one another such that, for the most part, it behaves as a stochastic control system. Neurons distributed throughout this hierarchy interconnect via specific linkages such that each neuronal cell station is involved in temporally dependent cardio-cardiac reflexes that control overlapping, spatially organized cardiac regions. Its function depends primarily, but not exclusively, on inputs arising from afferent neurons transducing the cardiovascular milieu to directly or indirectly (via interconnecting neurons) modify cardiac motor neurons coordinating regional cardiac behavior. As the function of the whole is greater than that of its individual parts, stable cardiac control occurs most of the time in the absence of direct cause and effect. During altered cardiac status, its redundancy normally represents a stabilizing feature. However, in the presence of regional myocardial ischemia, components within the intrinsic cardiac nervous system undergo pathological change. That, along with any consequent remodeling of the cardiac neuronal hierarchy, alters its spatially and temporally organized reflexes such that populations of neurons, acting in isolation, may destabilize efferent neuronal control of regional cardiac electrical and/or mechanical events.

  12. Microglia M2A Polarization as Potential Link between Food Allergy and Autism Spectrum Disorders.

    PubMed

    Kalkman, Hans O; Feuerbach, Dominik

    2017-12-09

    Atopic diseases are frequently co-morbid with autism spectrum disorders (ASD). Allergic responses are associated with an activation of mast cells, innate lymphoid cells, and Th2 cells. These cells produce type-2 cytokines (IL4 and IL13), which stimulate microglia and macrophages to adopt a phenotype referred to as 'alternative activation' or 'M2A'. M2A-polarized macrophages and microglia play a physiological role in tissue repair by secreting growth factors such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1. In ASD there is evidence for increased type-2 cytokines, microglia activation, M2A polarization, and increased levels of growth factors. In neurons, these growth factors drive a signal transduction pathway that leads to activation of the enzyme mammalian Target of Rapamycin (mTOR), and thereby to the inhibition of autophagy. Activation of mTOR is an effect that is also common to several of the genetic forms of autism. In the central nervous system, redundant synapses are removed via an autophagic process. Activation of mTOR would diminish the pruning of redundant synapses, which in the context of ASD is likely to be undesired. Based on this line of reasoning, atopic diseases like food allergy, eczema or asthma would represent risk factors for autism spectrum disorders.

  13. Mars Science Laboratory Sample Acquisition, Sample Processing and Handling: Subsystem Design and Test Challenges

    NASA Technical Reports Server (NTRS)

    Jandura, Louise

    2010-01-01

    The Sample Acquisition/Sample Processing and Handling subsystem for the Mars Science Laboratory is a highly-mechanized, Rover-based sampling system that acquires powdered rock and regolith samples from the Martian surface, sorts the samples into fine particles through sieving, and delivers small portions of the powder into two science instruments inside the Rover. SA/SPaH utilizes 17 actuated degrees-of-freedom to perform the functions needed to produce 5 sample pathways in support of the scientific investigation on Mars. Both hardware redundancy and functional redundancy are employed in configuring this sampling system so some functionality is retained even with the loss of a degree-of-freedom. Intentional dynamic environments are created to move sample while vibration isolators attenuate this environment at the sensitive instruments located near the dynamic sources. In addition to the typical flight hardware qualification test program, two additional types of testing are essential for this kind of sampling system: characterization of the intentionally-created dynamic environment and testing of the sample acquisition and processing hardware functions using Mars analog materials in a low pressure environment. The overall subsystem design and configuration are discussed along with some of the challenges, tradeoffs, and lessons learned in the areas of fault tolerance, intentional dynamic environments, and special testing

  14. Innate Immune Response to Streptococcus pyogenes Depends on the Combined Activation of TLR13 and TLR2

    PubMed Central

    Fieber, Christina; Janos, Marton; Koestler, Tina; Gratz, Nina; Li, Xiao-Dong; Castiglia, Virginia; Aberle, Marion; Sauert, Martina; Wegner, Mareike; Alexopoulou, Lena; Kirschning, Carsten J.; Chen, Zhijian J.; von Haeseler, Arndt; Kovarik, Pavel

    2015-01-01

    Innate immune recognition of the major human-specific Gram-positive pathogen Streptococcus pyogenes is not understood. Here we show that mice employ Toll-like receptor (TLR) 2- and TLR13-mediated recognition of S. pyogenes. These TLR pathways are non-redundant in the in vivo context of animal infection, but are largely redundant in vitro, as only inactivation of both of them abolishes inflammatory cytokine production by macrophages and dendritic cells infected with S. pyogenes. Mechanistically, S. pyogenes is initially recognized in a phagocytosis-independent manner by TLR2 and subsequently by TLR13 upon internalization. We show that the TLR13 response is specifically triggered by S. pyogenes rRNA and that Tlr13 −/− cells respond to S. pyogenes infection solely by engagement of TLR2. TLR13 is absent from humans and, remarkably, we find no equivalent route for S. pyogenes RNA recognition in human macrophages. Phylogenetic analysis reveals that TLR13 occurs in all kingdoms but only in few mammals, including mice and rats, which are naturally resistant against S. pyogenes. Our study establishes that the dissimilar expression of TLR13 in mice and humans has functional consequences for recognition of S. pyogenes in these organisms. PMID:25756897

  15. Plasticity of genetic interactions in metabolic networks of yeast.

    PubMed

    Harrison, Richard; Papp, Balázs; Pál, Csaba; Oliver, Stephen G; Delneri, Daniela

    2007-02-13

    Why are most genes dispensable? The impact of gene deletions may depend on the environment (plasticity), the presence of compensatory mechanisms (mutational robustness), or both. Here, we analyze the interaction between these two forces by exploring the condition-dependence of synthetic genetic interactions that define redundant functions and alternative pathways. We performed systems-level flux balance analysis of the yeast (Saccharomyces cerevisiae) metabolic network to identify genetic interactions and then tested the model's predictions with in vivo gene-deletion studies. We found that the majority of synthetic genetic interactions are restricted to certain environmental conditions, partly because of the lack of compensation under some (but not all) nutrient conditions. Moreover, the phylogenetic cooccurrence of synthetically interacting pairs is not significantly different from random expectation. These findings suggest that these gene pairs have at least partially independent functions, and, hence, compensation is only a byproduct of their evolutionary history. Experimental analyses that used multiple gene deletion strains not only confirmed predictions of the model but also showed that investigation of false predictions may both improve functional annotation within the model and also lead to the discovery of higher-order genetic interactions. Our work supports the view that functional redundancy may be more apparent than real, and it offers a unified framework for the evolution of environmental adaptation and mutational robustness.

  16. Nuclear import of human MLH1, PMS2, and MutLalpha: redundancy is the key.

    PubMed

    Leong, Vivian; Lorenowicz, Jessica; Kozij, Natalie; Guarné, Alba

    2009-08-01

    DNA mismatch repair maintains genomic stability by correcting errors that have escaped polymerase proofreading. Defects on mismatch repair genes lead to an increased mutation rate, microsatellite instability and predisposition to human non-polyposis colorectal cancer (HNPCC). Human MutLalpha is a heterodimer formed by the interaction of MLH1 and PMS2 that coordinates a series of key events in mismatch repair. It has been proposed that nuclear import of MutLalpha may be the first regulatory step on the activation of the mismatch repair pathway. Using confocal microscopy and mismatch repair deficient cells, we have identified the sequence determinants that drive nuclear import of human MLH1, PMS2, and MutLalpha. Transient transfection of the individual proteins reveals that MLH1 has a bipartite and PMS2 has a single monopartite nuclear localization signal. Although dimerization is not required for nuclear localization, the MutLalpha heterodimer is imported more efficiently than the MLH1 or PMS2 monomers. Interestingly, the bipartite localization signal of MLH1 can direct import of MutLalpha even when PMS2 encompasses a mutated localization signal. Hence we conclude that the presence of redundant nuclear localization signals guarantees nuclear transport of MutLalpha and, consequently, efficient mismatch repair.

  17. Rationale for selection of a flight control system for lift cruise fan V/STOL aircraft

    NASA Technical Reports Server (NTRS)

    Konsewicz, R. K.

    1977-01-01

    Various features of the lift cruise fan V/STOL concept are briefly reviewed. The ability to operate from small ships in adverse weather, low visibility, and rough sea conditions is emphasized as is the need for a highly capable, flexible, and reliabile flight control system. A three channel control by wire, digital flight control system is suggested. The requirement for automatic flight control, the advantage of control by wire implementation, the preference for a digital computer, and the need for three channel redundancy are among the factors discussed.

  18. Redundancy allocation problem for k-out-of- n systems with a choice of redundancy strategies

    NASA Astrophysics Data System (ADS)

    Aghaei, Mahsa; Zeinal Hamadani, Ali; Abouei Ardakan, Mostafa

    2017-03-01

    To increase the reliability of a specific system, using redundant components is a common method which is called redundancy allocation problem (RAP). Some of the RAP studies have focused on k-out-of- n systems. However, all of these studies assumed predetermined active or standby strategies for each subsystem. In this paper, for the first time, we propose a k-out-of- n system with a choice of redundancy strategies. Therefore, a k-out-of- n series-parallel system is considered when the redundancy strategy can be chosen for each subsystem. In other words, in the proposed model, the redundancy strategy is considered as an additional decision variable and an exact method based on integer programming is used to obtain the optimal solution of the problem. As the optimization of RAP belongs to the NP-hard class of problems, a modified version of genetic algorithm (GA) is also developed. The exact method and the proposed GA are implemented on a well-known test problem and the results demonstrate the efficiency of the new approach compared with the previous studies.

  19. QFT Multi-Input, Multi-Output Design with Non-Diagonal, Non-Square Compensation Matrices

    NASA Technical Reports Server (NTRS)

    Hess, R. A.; Henderson, D. K.

    1996-01-01

    A technique for obtaining a non-diagonal compensator for the control of a multi-input, multi-output plant is presented. The technique, which uses Quantitative Feedback Theory, provides guaranteed stability and performance robustness in the presence of parametric uncertainty. An example is given involving the lateral-directional control of an uncertain model of a high-performance fighter aircraft in which redundant control effectors are in evidence, i.e. more control effectors than output variables are used.

  20. Proof of Concept: A review on how network and systems biology approaches aid in the discovery of potent anticancer drug combinations

    PubMed Central

    Azmi, Asfar S.; Wang, Zhiwei; Philip, Philip A.; Mohammad, Ramzi M.; Sarkar, Fazlul H.

    2010-01-01

    Cancer therapies that target key molecules have not fulfilled expected promises for most common malignancies. Major challenges include the incomplete understanding and validation of these targets in patients, the multiplicity and complexity of genetic and epigenetic changes in the majority of cancers, and the redundancies and cross-talk found in key signaling pathways. Collectively, the uses of single-pathway targeted approaches are not effective therapies for human malignances. To overcome these barriers, it is important to understand the molecular cross-talk among key signaling pathways and how they may be altered by targeted agents. This requires innovative approaches such as understanding the global physiological environment of target proteins and the effects of modifying them without losing key molecular details. Such strategies will aid the design of novel therapeutics and their combinations against multifaceted diseases where efficacious combination therapies will focus on altering multiple pathways rather than single proteins. Integrated network modeling and systems biology has emerged as a powerful tool benefiting our understanding of drug mechanism of action in real time. This mini-review highlights the significance of the network and systems biology-based strategy and presents a “proof-of-concept” recently validated in our laboratory using the example of a combination treatment of oxaliplatin and the MDM2 inhibitor MI-219 in genetically complex and incurable pancreatic adenocarcinoma. PMID:21041384

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