Reducing airflow energy use in multiple zone vav systems
NASA Astrophysics Data System (ADS)
Tukur, Ahmed Gidado
Variable Air Volume (VAV) systems are the most popular HVAC systems in commercial buildings. VAV systems are designed to deliver airflows at design conditions which only occur for a few hours in a year. Minimizing energy use in VAV systems requires reducing the amount of airflow delivered through the system at part load conditions. Air Handling Unit (AHU) fans are the major drivers of airflow in VAV systems and installing a Variable Frequency Drive (VFD) is the most common method of regulating airflow in VAV systems. A VFD drive does not necessarily save energy without use of an appropriate control strategy. Static pressure reset (SPR) is considered to be the most energy efficient control strategy for AHU fans with VFDs installed. The implementation of SPR however has many challenges; for example, rogue zones--zones which have faulty sensors or failed controls and actuators, system dynamics like hunting and system diversity. By investigating the parameters associated with the implementation of SPR in VAV systems, a new, improved, more stable SPR algorithm was developed and validated. This approach was further improved using Fault Detection and Diagnostics (FDD) to eliminate rogue zones. Additionally, a CO2-Demand Control Ventilation (DCV) based minimum airflow control was used to further reduce ventilation airflow and save more energy from SPR. Energy savings ranging from 25% to 51% were recorded in actual buildings with the new SPR algorithm. Finally, a methodology that utilizes historical VAV data was developed to estimate the potential savings that could be realized using SPR. The approach employed first determines an effective system loss coefficient as a function of mean damper position using the historical duct static pressure, VAV damper positions and airflows. Additionally, the historical data is used to identify the maximum mean duct damper position realizable as a result of insuring a sufficient number of VAVs are fully open at any time. Savings are estimated by shifting the damper distribution mean at each time to this maximum value and reducing the static pressure to achieve the same overall system airflow rate. The methodology was tested on three different buildings with varying system characteristics. Savings estimates correlated well to the savings actually realized from SPR. This result has significant implications for energy service providers, who could use the predictions to guarantee savings from SPR.
Pauker, Maor H; Hassan, Nirit; Noy, Elad; Reicher, Barak; Barda-Saad, Mira
2012-04-24
Protein-protein interactions regulate and control many cellular functions. A multimolecular complex consisting of the adaptor proteins SLP-76 (Src homology 2 domain-containing leukocyte protein of 76 kD), Nck, and the guanine nucleotide exchange factor Vav1 is recruited to the T cell side of the interface with an antigen-presenting cell during initial T cell activation. This complex is crucial for regulation of the actin machinery, antigen recognition, and signaling in T cells. We studied the interactions between these proteins as well as the dynamics of their recruitment into a complex that governs cytoskeletal reorganization. We developed a triple-color Förster resonance energy transfer (3FRET) system to observe the dynamics of the formation of this trimolecular signaling complex in live human T cells and to follow the three molecular interactions in parallel. Using the 3FRET system, we demonstrated that dimers of Nck and Vav1 were constitutively formed independently of both T cell activation and the association between SLP-76 and Nck. After T cell receptor stimulation, SLP-76 was phosphorylated, which enabled the binding of Nck. A point mutation in the proline-rich site of Vav1, which abolishes its binding to Nck, impaired actin rearrangement, suggesting that Nck-Vav1 dimers play a critical role in regulation of the actin machinery. We suggest that these findings revise the accepted model of the formation of a complex of SLP-76, Nck, and Vav1 and demonstrate the use of 3FRET as a tool to study signal transduction in live cells.
Strijbis, Karin; Tafesse, Fikadu G.; Fairn, Gregory D.; Witte, Martin D.; Dougan, Stephanie K.; Watson, Nicki; Spooner, Eric; Esteban, Alexandre; Vyas, Valmik K.; Fink, Gerald R.; Grinstein, Sergio; Ploegh, Hidde L.
2013-01-01
Phagocytosis of the opportunistic fungal pathogen Candida albicans by cells of the innate immune system is vital to prevent infection. Dectin-1 is the major phagocytic receptor involved in anti-fungal immunity. We identify two new interacting proteins of Dectin-1 in macrophages, Bruton's Tyrosine Kinase (BTK) and Vav1. BTK and Vav1 are recruited to phagocytic cups containing C. albicans yeasts or hyphae but are absent from mature phagosomes. BTK and Vav1 localize to cuff regions surrounding the hyphae, while Dectin-1 lines the full length of the phagosome. BTK and Vav1 colocalize with the lipid PI(3,4,5)P3 and F-actin at the phagocytic cup, but not with diacylglycerol (DAG) which marks more mature phagosomal membranes. Using a selective BTK inhibitor, we show that BTK contributes to DAG synthesis at the phagocytic cup and the subsequent recruitment of PKCε. BTK- or Vav1-deficient peritoneal macrophages display a defect in both zymosan and C. albicans phagocytosis. Bone marrow-derived macrophages that lack BTK or Vav1 show reduced uptake of C. albicans, comparable to Dectin1-deficient cells. BTK- or Vav1-deficient mice are more susceptible to systemic C. albicans infection than wild type mice. This work identifies an important role for BTK and Vav1 in immune responses against C. albicans. PMID:23825946
Strijbis, Karin; Tafesse, Fikadu G; Fairn, Gregory D; Witte, Martin D; Dougan, Stephanie K; Watson, Nicki; Spooner, Eric; Esteban, Alexandre; Vyas, Valmik K; Fink, Gerald R; Grinstein, Sergio; Ploegh, Hidde L
2013-01-01
Phagocytosis of the opportunistic fungal pathogen Candida albicans by cells of the innate immune system is vital to prevent infection. Dectin-1 is the major phagocytic receptor involved in anti-fungal immunity. We identify two new interacting proteins of Dectin-1 in macrophages, Bruton's Tyrosine Kinase (BTK) and Vav1. BTK and Vav1 are recruited to phagocytic cups containing C. albicans yeasts or hyphae but are absent from mature phagosomes. BTK and Vav1 localize to cuff regions surrounding the hyphae, while Dectin-1 lines the full length of the phagosome. BTK and Vav1 colocalize with the lipid PI(3,4,5)P3 and F-actin at the phagocytic cup, but not with diacylglycerol (DAG) which marks more mature phagosomal membranes. Using a selective BTK inhibitor, we show that BTK contributes to DAG synthesis at the phagocytic cup and the subsequent recruitment of PKCε. BTK- or Vav1-deficient peritoneal macrophages display a defect in both zymosan and C. albicans phagocytosis. Bone marrow-derived macrophages that lack BTK or Vav1 show reduced uptake of C. albicans, comparable to Dectin1-deficient cells. BTK- or Vav1-deficient mice are more susceptible to systemic C. albicans infection than wild type mice. This work identifies an important role for BTK and Vav1 in immune responses against C. albicans.
Vav1 GEF activity is required for T cell mediated allograft rejection
Haubert, Dirk; Li, Jianping; Saveliev, Alexander; Calzascia, Thomas; Sutter, Esther; Metzler, Barbara; Kaiser, Daniel; Tybulewicz, Victor L.J.; Weckbecker, Gisbert
2012-01-01
The GDP exchange factor (GEF) Vav1 is a central signal transducer downstream of the T cell receptor and has been identified as a key factor for T cell activation in the context of allograft rejection. Vav1 has been shown to transduce signals both dependent and independent of its GEF function. The most promising approach to disrupt Vav1 activity by pharmacological inhibition would be to target its GEF function. However, the contribution of Vav1 GEF activity for allogeneic T cell activation has not been clarified yet. To address this question, we used knock-in mice bearing a mutated Vav1 with disrupted GEF activity but intact GEF-independent functions. T cells from these mice showed strongly reduced proliferation and activation in response to allogeneic stimulation. Furthermore, lack of Vav1 GEF activity strongly abrogated the in vivo expansion of T cells in a systemic graft-versus-host model. In a cardiac transplantation model, mice with disrupted Vav1 GEF activity show prolonged allograft survival. These findings demonstrate a strong requirement for Vav1 GEF activity for allogeneic T cell activation and graft rejection suggesting that disruption of Vav1 GEF activity alone is sufficient to induce significant immunosuppression. PMID:22456277
Gomez-Marcos, Manuel A; Gonzalez-Sarmiento, Rogelio; Recio-Rodríguez, José I; Agudo-Conde, Cristina; Gamella-Pozuelo, Luis; Perretta-Tejedor, Nuria; Martínez-Salgado, Carlos; García-Ortiz, Luis
2014-04-03
Target organ damage (TOD) is associated with increased cardiovascular risk. The study objectives were to analyse the relationship of TOD to blood pressure, size of retinal arteries and veins, oxidative stress and different polymorphisms in the VAV-2 and VAV-3 genes in participants with hypertension. A case-control study to analyse the relationship between clinical, biochemical and genetic parameters and presence of cardiac, vascular and renal TOD in 486 patients with hypertension. Participants with TOD will be considered as cases, and those without TOD will be enrolled as controls. This will be a collaborative study conducted by the groups of Primary Care, Cardiovascular and Metabolic and Degenerative Diseases of the Instituto de Investigación Biomédica of Salamanca (IBSAL). Assessment of cardiac, renal and vascular TOD. Measurement of peripheral and central blood pressure, size of eye fundus arteries and veins, and oxidative stress, and polymorphisms in the VAV-2 and VAV-3 genes. The study will be conducted after approval is obtained from the Ethics Committee of Hospital Clínico Universitario of Salamanca. All study participants will sign an informed consent to agree to participate in the study, and another consent to agree on the genetic study, in compliance with the Declaration of Helsinki and the WHO standards for observational studies. The results of this study will allow for an understanding of the relationship of the different TODs with blood pressure, retinal artery and vein diameters, oxidative stress and polymorphisms in VAV-2 and VAV-3 genes. Clinical Trials. gov Identifier: NCT02022618.
Gomez-Marcos, Manuel A; Gonzalez-Sarmiento, Rogelio; Recio-Rodríguez, José I; Agudo-Conde, Cristina; Gamella-Pozuelo, Luis; Perretta-Tejedor, Nuria; Martínez-Salgado, Carlos; García-Ortiz, Luis
2014-01-01
Introduction Target organ damage (TOD) is associated with increased cardiovascular risk. The study objectives were to analyse the relationship of TOD to blood pressure, size of retinal arteries and veins, oxidative stress and different polymorphisms in the VAV-2 and VAV-3 genes in participants with hypertension. Methods and analysis A case–control study to analyse the relationship between clinical, biochemical and genetic parameters and presence of cardiac, vascular and renal TOD in 486 patients with hypertension. Participants with TOD will be considered as cases, and those without TOD will be enrolled as controls. This will be a collaborative study conducted by the groups of Primary Care, Cardiovascular and Metabolic and Degenerative Diseases of the Instituto de Investigación Biomédica of Salamanca (IBSAL). Assessment of cardiac, renal and vascular TOD. Measurement of peripheral and central blood pressure, size of eye fundus arteries and veins, and oxidative stress, and polymorphisms in the VAV-2 and VAV-3 genes. Ethics and dissemination The study will be conducted after approval is obtained from the Ethics Committee of Hospital Clínico Universitario of Salamanca. All study participants will sign an informed consent to agree to participate in the study, and another consent to agree on the genetic study, in compliance with the Declaration of Helsinki and the WHO standards for observational studies. The results of this study will allow for an understanding of the relationship of the different TODs with blood pressure, retinal artery and vein diameters, oxidative stress and polymorphisms in VAV-2 and VAV-3 genes. Trial registration number Clinical Trials. gov Identifier: NCT02022618. PMID:24699462
Vav1 GEF activity is required for T cell mediated allograft rejection.
Haubert, Dirk; Li, Jianping; Saveliev, Alexander; Calzascia, Thomas; Sutter, Esther; Metzler, Barbara; Kaiser, Daniel; Tybulewicz, Victor L J; Weckbecker, Gisbert
2012-06-01
The GDP exchange factor (GEF) Vav1 is a central signal transducer downstream of the T cell receptor and has been identified as a key factor for T cell activation in the context of allograft rejection. Vav1 has been shown to transduce signals both dependent and independent of its GEF function. The most promising approach to disrupt Vav1 activity by pharmacological inhibition would be to target its GEF function. However, the contribution of Vav1 GEF activity for allogeneic T cell activation has not been clarified yet. To address this question, we used knock-in mice bearing a mutated Vav1 with disrupted GEF activity but intact GEF-independent functions. T cells from these mice showed strongly reduced proliferation and activation in response to allogeneic stimulation. Furthermore, lack of Vav1 GEF activity strongly abrogated the in vivo expansion of T cells in a systemic graft-versus-host model. In a cardiac transplantation model, mice with disrupted Vav1 GEF activity show prolonged allograft survival. These findings demonstrate a strong requirement for Vav1 GEF activity for allogeneic T cell activation and graft rejection suggesting that disruption of Vav1 GEF activity alone is sufficient to induce significant immunosuppression. Copyright © 2012 Elsevier B.V. All rights reserved.
CO2 concentration and occupancy density in the critical zones served by the VAV system
NASA Astrophysics Data System (ADS)
Etoua Evina, Ghislaine; Kajl, Stanislaw; Lamarche, Louis; Beltran-Galindo, Javier
2017-11-01
This article presents the results obtained from monitoring a VAV system with highly diversified zone occupancy density are presented in the article. The investigated VAV system meets the load for 72 zones (68 perimeters and 4 interiors) consisting of classrooms, offices, conference rooms, etc. with highly diversified occupancy densities from 1.875 to 2.5 m2/person for the classrooms and from 10 to 15 m2/person for the offices. The monitoring shows that the CO2 concentration can exceed the set point in the critical rooms. Simulation results are also presented in the article to show that it is often impossible to adjust the operation of such VAV systems because the adjusted System Outdoor Air Fractions, % OA, can reach 100% even where the zone CO2 concentration is not respected. The presented monitoring and simulation results were obtained in the winter, with the VAV system operating at partial load and with the minimum outdoor air flowrate required by the economizer system. As shown in the article, to respect the zone set point CO2 concentration in such period, the VAV system must operate mostly at a %OA equal to 100% instead of its minimum value. To circumvent this, the supply zone air flow rate may have to be designed taking into account the CO2 concentration resulting from the critical zones occupancy density.
Graham, Daniel B.; Robertson, Charles M.; Bautista, Jhoanne; Mascarenhas, Francesca; Diacovo, M. Julia; Montgrain, Vivianne; Lam, Siu Kit; Cremasco, Viviana; Dunne, W. Michael; Faccio, Roberta; Coopersmith, Craig M.; Swat, Wojciech
2007-01-01
Oxidative burst, a critical antimicrobial mechanism of neutrophils, involves the rapid generation and release of reactive oxygen intermediates (ROIs) by the NADPH oxidase complex. Genetic mutations in an NADPH oxidase subunit, gp91 (also referred to as NOX2), are associated with chronic granulomatous disease (CGD), which is characterized by recurrent and life-threatening microbial infections. To combat such infections, ROIs are produced by neutrophils after stimulation by integrin-dependent adhesion to the ECM in conjunction with stimulation from inflammatory mediators, or microbial components containing pathogen-associated molecular patterns. In this report, we provide genetic evidence that both the Vav family of Rho GTPase guanine nucleotide exchange factors (GEFs) and phospholipase C–γ2 (PLC-γ2) are critical mediators of adhesion-dependent ROI production by neutrophils in mice. We also demonstrated that Vav was critically required for neutrophil-dependent host defense against systemic infection by Staphylococcus aureus and Pseudomonas aeruginosa, 2 common pathogens associated with fatal cases of hospital-acquired pneumonia. We identified a molecular pathway in which Vav GEFs linked integrin-mediated signaling with PLC-γ2 activation, release of intracellular Ca2+ cations, and generation of diacylglycerol to control assembly of the NADPH oxidase complex and ROI production by neutrophils. Taken together, our data indicate that integrin-dependent signals generated during neutrophil adhesion contribute to the activation of NADPH oxidase by a variety of distinct effector pathways, all of which require Vav. PMID:17932569
VAV-1 acts in a single interneuron to inhibit motor circuit activity in Caenorhabditis elegans.
Fry, Amanda L; Laboy, Jocelyn T; Norman, Kenneth R
2014-11-21
The complex molecular and cellular mechanisms underlying neuronal control of animal movement are not well understood. Locomotion of Caenorhabditis elegans is mediated by a neuronal circuit that produces coordinated sinusoidal movement. Here we utilize this simple, yet elegant, behaviour to show that VAV-1, a conserved guanine nucleotide exchange factor for Rho-family GTPases, negatively regulates motor circuit activity and the rate of locomotion. While vav-1 is expressed in a small subset of neurons, we find that VAV-1 function is required in a single interneuron, ALA, to regulate motor neuron circuit activity. Furthermore, we show by genetic and optogenetic manipulation of ALA that VAV-1 is required for the excitation and activation of this neuron. We find that ALA signalling inhibits command interneuron activity by abrogating excitatory signalling in the command interneurons, which is responsible for promoting motor neuron circuit activity. Together, our data describe a novel neuromodulatory role for VAV-1-dependent signalling in the regulation of motor circuit activity and locomotion.
Sylvain, Nicholas R.; Nguyen, Ken; Bunnell, Stephen C.
2013-01-01
The guanine nucleotide exchange factor (GEF) Vav1 synergizes with the adapter SLP-76 to support T cell development and activation. Here, we demonstrate that Vav1 controls the stability and movement T cell receptor-induced SLP-76 microclusters. The SH2 domain enables the recruitment of Vav1 into SLP-76 microclusters, whereas the SH3 domains of Vav1 cooperate to enhance microcluster stability and function. Although the amino-terminus of Vav1 is essential for downstream signaling, it possesses novel scaffolding functions that are unaffected by the inactivation of the Vav1 GEF or by the constitutive GEF activation that accompanies the mutation of the regulatory tyrosine residues 142, 160, and 174. In contrast, GEF-inactivating point mutations predicted to perturb the structural integrity of the Vav1 GEF abolish these scaffolding functions. Paradoxically, the excision of catalytic Dbl-homology (DH) / pleckstrin homology (PH) cassette produces a relatively mild scaffolding defect, indicating that the L213A and L278Q point mutations antagonize scaffolding functions mediated by adjacent domains. A deletion mutant lacking the CH domain potently inhibits calcium responses, but also exhibits mild scaffolding defects. We conclude multiple GEF-independent scaffolding functions contained within the amino-terminus of Vav1 contribute to T cell activation by acting synergistically to increase the stability and functionality of SLP-76 microclusters. PMID:21386095
Kim, Dongsu; Cox, Sam J.; Cho, Heejin; ...
2017-05-22
Variable refrigerant flow (VRF) systems are known for their high energy performance and thus can improve energy efficiency both in residential and commercial buildings. The energy savings potential of this system has been demonstrated in several studies by comparing the system performance with conventional HVAC systems such as rooftop variable air volume systems (RTU-VAV) and central chiller and boiler systems. This paper evaluates the performance of VRF and RTU-VAV systems in a simulation environment using widely-accepted whole building energy modeling software, EnergyPlus. A medium office prototype building model, developed by the U.S. Department of Energy (DOE), is used to assessmore » the performance of VRF and RTU-VAV systems. Each system is placed in 16 different locations, representing all U.S. climate zones, to evaluate the performance variations. Both models are compliant with the minimum energy code requirements prescribed in ASHRAE standard 90.1-2010 — energy standard for buildings except low-rise residential buildings. Finally, a comparison study between the simulation results of VRF and RTU-VAV models is made to demonstrate energy savings potential of VRF systems. The simulation results show that the VRF systems would save around 15–42% and 18–33% for HVAC site and source energy uses compared to the RTU-VAV systems. In addition, calculated results for annual HVAC cost savings point out that hot and mild climates show higher percentage cost savings for the VRF systems than cold climates mainly due to the differences in electricity and gas use for heating sources.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Dongsu; Cox, Sam J.; Cho, Heejin
Variable refrigerant flow (VRF) systems are known for their high energy performance and thus can improve energy efficiency both in residential and commercial buildings. The energy savings potential of this system has been demonstrated in several studies by comparing the system performance with conventional HVAC systems such as rooftop variable air volume systems (RTU-VAV) and central chiller and boiler systems. This paper evaluates the performance of VRF and RTU-VAV systems in a simulation environment using widely-accepted whole building energy modeling software, EnergyPlus. A medium office prototype building model, developed by the U.S. Department of Energy (DOE), is used to assessmore » the performance of VRF and RTU-VAV systems. Each system is placed in 16 different locations, representing all U.S. climate zones, to evaluate the performance variations. Both models are compliant with the minimum energy code requirements prescribed in ASHRAE standard 90.1-2010 — energy standard for buildings except low-rise residential buildings. Finally, a comparison study between the simulation results of VRF and RTU-VAV models is made to demonstrate energy savings potential of VRF systems. The simulation results show that the VRF systems would save around 15–42% and 18–33% for HVAC site and source energy uses compared to the RTU-VAV systems. In addition, calculated results for annual HVAC cost savings point out that hot and mild climates show higher percentage cost savings for the VRF systems than cold climates mainly due to the differences in electricity and gas use for heating sources.« less
Kassem, Sahar; Gaud, Guillaume; Bernard, Isabelle; Benamar, Mehdi; Dejean, Anne S; Liblau, Roland; Fournié, Gilbert J; Colacios, Céline; Malissen, Bernard; Saoudi, Abdelhadi
2016-07-01
The guanine nucleotide exchange factor Vav1 is essential for transducing T cell antigen receptor signals and therefore plays an important role in T cell development and activation. Our previous genetic studies identified a locus on rat chromosome 9 that controls the susceptibility to neuroinflammation and contains a non-synonymous polymorphism in the major candidate gene Vav1. To formally demonstrate the causal implication of this polymorphism, we generated a knock-in mouse bearing this polymorphism (Vav1R63W). Using this model, we show that Vav1R63W mice display reduced susceptibility to experimental autoimmune encephalomyelitis (EAE) induced by MOG35-55 peptide immunization. This is associated with a lower production of effector cytokines (IFN-γ, IL-17 and GM-CSF) by autoreactive CD4 T cells. Despite increased proportion of Foxp3+ regulatory T cells in Vav1R63W mice, we show that this lowered cytokine production is intrinsic to effector CD4 T cells and that Treg depletion has no impact on EAE development. Finally, we provide a mechanism for the above phenotype by showing that the Vav1R63W variant has normal enzymatic activity but reduced adaptor functions. Together, these data highlight the importance of Vav1 adaptor functions in the production of inflammatory cytokines by effector T cells and in the susceptibility to neuroinflammation.
Kassem, Sahar; Bernard, Isabelle; Dejean, Anne S.; Liblau, Roland; Fournié, Gilbert J.; Colacios, Céline
2016-01-01
The guanine nucleotide exchange factor Vav1 is essential for transducing T cell antigen receptor signals and therefore plays an important role in T cell development and activation. Our previous genetic studies identified a locus on rat chromosome 9 that controls the susceptibility to neuroinflammation and contains a non-synonymous polymorphism in the major candidate gene Vav1. To formally demonstrate the causal implication of this polymorphism, we generated a knock-in mouse bearing this polymorphism (Vav1R63W). Using this model, we show that Vav1R63W mice display reduced susceptibility to experimental autoimmune encephalomyelitis (EAE) induced by MOG35-55 peptide immunization. This is associated with a lower production of effector cytokines (IFN-γ, IL-17 and GM-CSF) by autoreactive CD4 T cells. Despite increased proportion of Foxp3+ regulatory T cells in Vav1R63W mice, we show that this lowered cytokine production is intrinsic to effector CD4 T cells and that Treg depletion has no impact on EAE development. Finally, we provide a mechanism for the above phenotype by showing that the Vav1R63W variant has normal enzymatic activity but reduced adaptor functions. Together, these data highlight the importance of Vav1 adaptor functions in the production of inflammatory cytokines by effector T cells and in the susceptibility to neuroinflammation. PMID:27438086
Pedros, Christophe; Gaud, Guillaume; Bernard, Isabelle; Kassem, Sahar; Chabod, Marianne; Lagrange, Dominique; Andréoletti, Olivier; Dejean, Anne S; Lesourne, Renaud; Fournié, Gilbert J; Saoudi, Abdelhadi
2015-08-15
The development of inflammatory diseases depends on complex interactions between several genes and various environmental factors. Discovering new genetic risk factors and understanding the mechanisms whereby they influence disease development is of paramount importance. We previously reported that deficiency in Themis1, a new actor of TCR signaling, impairs regulatory T cell (Treg) function and predisposes Brown-Norway (BN) rats to spontaneous inflammatory bowel disease (IBD). In this study, we reveal that the epistasis between Themis1 and Vav1 controls the occurrence of these phenotypes. Indeed, by contrast with BN rats, Themis1 deficiency in Lewis rats neither impairs Treg suppressive functions nor induces pathological manifestations. By using congenic lines on the BN genomic background, we show that the impact of Themis1 deficiency on Treg suppressive functions depends on a 117-kb interval coding for a R63W polymorphism that impacts Vav1 expression and functions. Indeed, the introduction of a 117-kb interval containing the Lewis Vav1-R63 variant restores Treg function and protects Themis1-deficient BN rats from spontaneous IBD development. We further show that Themis1 binds more efficiently to the BN Vav1-W63 variant and is required to stabilize its recruitment to the transmembrane adaptor LAT and to fully promote the activation of Erk kinases. Together, these results highlight the importance of the signaling pathway involving epistasis between Themis1 and Vav1 in the control of Treg suppressive function and susceptibility to IBD development. Copyright © 2015 by The American Association of Immunologists, Inc.
Association of VAV2 and VAV3 polymorphisms with cardiovascular risk factors
Perretta-Tejedor, Nuria; Fernández-Mateos, Javier; García-Ortiz, Luis; Gómez-Marcos, Manuel A.; Recio-Rodríguez, José I.; Agudo-Conde, Cristina; Rodriguez-Sánchez, Emiliano; Morales, Ana I.; López-Hernández, Francisco J.; López-Novoa, José M.; González-Sarmiento, Rogelio; Martínez-Salgado, Carlos
2017-01-01
Hypertension, diabetes and obesity are cardiovascular risk factors closely associated to the development of renal and cardiovascular target organ damage. VAV2 and VAV3, members of the VAV family proto-oncogenes, are guanosine nucleotide exchange factors for the Rho and Rac GTPase family, which is related with cardiovascular homeostasis. We have analyzed the relationship between the presence of VAV2 rs602990 and VAV3 rs7528153 polymorphisms with cardiovascular risk factors and target organ damage (heart, vessels and kidney) in 411 subjects. Our results show that being carrier of the T allele in VAV2 rs602990 polymorphism is associated with an increased risk of obesity, reduced levels of ankle-brachial index and diastolic blood pressure and reduced retinal artery caliber. In addition, being carrier of T allele is associated with increased risk of target organ damage in males. On the other hand, being carrier of the T allele in VAV3 rs7528153 polymorphism is associated with a decreased susceptibility of developing a pathologic state composed by the presence of hypertension, diabetes, obesity or cardiovascular damage, and with an increased risk of developing altered basal glycaemia. This is the first report showing an association between VAV2 and VAV3 polymorphisms with cardiovascular risk factors and target organ damage. PMID:28157227
New insights into the Vav1 activation cycle in lymphocytes.
Barreira, María; Rodríguez-Fdez, Sonia; Bustelo, Xosé R
2018-05-01
Vav1 is a hematopoietic-specific Rho GDP/GTP exchange factor and signaling adaptor. Although these activities are known to be stimulated by direct Vav1 phosphorylation, little information still exists regarding the regulatory layers that influence the overall Vav1 activation cycle. Using a collection of cell models and activation-mimetic Vav1 mutants, we show here that the dephosphorylated state of Vav1 in nonstimulated T cells requires the presence of a noncatalytic, phospholipase Cγ1-Slp76-mediated inhibitory pathway. Upon T cell stimulation, Vav1 becomes rapidly phosphorylated via the engagement of Lck and, to a much lesser extent, other Src family kinases and Zap70. In this process, Lck, Zap70 and the adaptor protein Lat contribute differently to the dynamics and amplitude of the Vav1 phosphorylated pool. Consistent with a multiphosphosite activation mechanism, the optimal stimulation of Vav1 can only be recapitulated by the combination of several activation-mimetic phosphosite mutants. The analysis of these mutants has also unveiled the presence of different Vav1 signaling competent states that are influenced by phosphosites present in the N- and C-terminal domains of the protein. Copyright © 2018 Elsevier Inc. All rights reserved.
Sylvain, Nicholas R; Nguyen, Ken; Bunnell, Stephen C
2011-03-08
The guanine nucleotide exchange factor (GEF) Vav1 synergizes with the adaptor protein SLP-76 (Src homology 2 domain--containing leukocyte phosphoprotein of 76 kD) to support T cell development and activation. In response to ligation of the T cell receptor (TCR), SLP-76 is assembled into microclusters that provide an essential platform for the signaling events that drive T cell activation. We found that Vav1 selectively entered SLP-76 microclusters, rather than TCR microclusters, influencing their stability and function. The carboxyl terminus of Vav1, which consists of Src homology domains, was both necessary and sufficient for the entry of Vav1 into SLP-76 microclusters; however, this fragment of Vav1 was insufficient to stabilize the microclusters, and it potently suppressed T cell activation. This indicated that the amino terminus of Vav1, which has the GEF domain, also contributed to the integrity of SLP-76 microclusters and thereby to T cell activation. These microcluster-stabilizing functions were independent of the GEF activity in the amino terminus of Vav1 and were unaffected if the GEF function of Vav1 was either inactivated or constitutively activated by mutation. In contrast, Vav1 deletion mutants lacking either the calponin homology domain or the catalytic core of the GEF exhibited mild scaffolding defects, but they differentially affected TCR-dependent calcium ion (Ca²+) responses. We conclude that multiple GEF-independent scaffolding functions distributed throughout the amino terminus of Vav1 contribute to the activation of T cells by acting synergistically to increase the stability and function of SLP-76 microclusters.
Direct Digital Control of HVAC (Heating, Ventilating, and Air Conditioning Equipment (User’s Guide)
1985-01-01
reset, load shedding, chiller optimization , VAV fan synchronization, and optimum start/stop. The prospective buyer of a DDC system should investigate...current and accurate drawings for a conventional, built-up control system such as that illustrated in Fig- ure 4. Data on setpoints , reset schedules, and...are always available in the form of the computer program code (Figure 7). In addition to the control logic, setpoint and other data are readily
Probing the Tyrosine Phosphorylation State in Breast Cancer by Src Homology 2 Domain Binding
2006-08-01
pervanadate, a potent tyrosine phosphatase inhibitor . In the absence of pervanadate, endogenous phosphatases very rapidly dephosphorylate tyrosine...Shd Loc90525 Crk CrkL Plcg1NCPlcg2NC P85aNC p55gNC Vav1 Vav2 Vav3 Tec Btk Emt Txk Bmx Slp76 Mist MistRK GapNC Chimerin Chimerin 2 Tensin Tem6 Tenc1...Plcg1NCPlcg2NC P85aNC Vav1 Vav2 Vav3 Tec Btk Emt Txk Bmx Slp76 Mist MistRK GapNC Chimerin Chimerin 2 Tensin Tem6 Tenc1 Cis1 Cten Nap4 Rin1 RIn2 Rin3
Molecular Basis for Failure of “Atypical” C1 Domain of Vav1 to Bind Diacylglycerol/Phorbol Ester*
Geczy, Tamas; Peach, Megan L.; El Kazzouli, Saïd; Sigano, Dina M.; Kang, Ji-Hye; Valle, Christopher J.; Selezneva, Julia; Woo, Wonhee; Kedei, Noemi; Lewin, Nancy E.; Garfield, Susan H.; Lim, Langston; Mannan, Poonam; Marquez, Victor E.; Blumberg, Peter M.
2012-01-01
C1 domains, the recognition motif of the second messenger diacylglycerol and of the phorbol esters, are classified as typical (ligand-responsive) or atypical (not ligand-responsive). The C1 domain of Vav1, a guanine nucleotide exchange factor, plays a critical role in regulation of Vav activity through stabilization of the Dbl homology domain, which is responsible for exchange activity of Vav. Although the C1 domain of Vav1 is classified as atypical, it retains a binding pocket geometry homologous to that of the typical C1 domains of PKCs. This study clarifies the basis for its failure to bind ligands. Substituting Vav1-specific residues into the C1b domain of PKCδ, we identified five crucial residues (Glu9, Glu10, Thr11, Thr24, and Tyr26) along the rim of the binding cleft that weaken binding potency in a cumulative fashion. Reciprocally, replacing these incompatible residues in the Vav1 C1 domain with the corresponding residues from PKCδ C1b (δC1b) conferred high potency for phorbol ester binding. Computer modeling predicts that these unique residues in Vav1 increase the hydrophilicity of the rim of the binding pocket, impairing membrane association and thereby preventing formation of the ternary C1-ligand-membrane binding complex. The initial design of diacylglycerol-lactones to exploit these Vav1 unique residues showed enhanced selectivity for C1 domains incorporating these residues, suggesting a strategy for the development of ligands targeting Vav1. PMID:22351766
Direct Digital Control of HVAC (Heating, Ventilating, and Air Conditioning).
1985-01-01
controller func- tions such as time-of-day, economizer cycles, reset, load shedding, chiller optimization , VAV fan synchronization, and optimum start/stop...control system such as that illustrated in Fig- urc 4. Data on setpoints , reset schedules, and event timing, such as that presented in Figure 6, are...program code (Figure 7). In addition to the control logic, setpoint and other data are readily available. Program logi:, setpoint and schedule data, and
Function of the nucleotide exchange activity of vav1 in T cell development and activation.
Saveliev, Alexander; Vanes, Lesley; Ksionda, Olga; Rapley, Jonathan; Smerdon, Stephen J; Rittinger, Katrin; Tybulewicz, Victor L J
2009-12-15
The guanine nucleotide exchange factor (GEF) Vav1 is essential for transducing T cell antigen receptor (TCR) signals and therefore plays a critical role in the development and activation of T cells. It has been presumed that the GEF activity of Vav1 is important for its function; however, there has been no direct demonstration of this. Here, we generated mice expressing enzymatically inactive, but normally folded, Vav1 protein. Analysis of these mice showed that the GEF activity of Vav1 was necessary for the selection of thymocytes and for the optimal activation of T cells, including signal transduction to Rac1, Akt, and integrins. In contrast, the GEF activity of Vav1 was not required for TCR-induced calcium flux, activation of extracellular signal-regulated kinase and protein kinase D1, and cell polarization. Thus, in T cells, the GEF activity of Vav1 is essential for some, but not all, of its functions.
Function of the Nucleotide Exchange Activity of Vav1 in T cell Development and Activation*
Saveliev, Alexander; Vanes, Lesley; Ksionda, Olga; Rapley, Jonathan; Smerdon, Stephen J.; Rittinger, Katrin; Tybulewicz, Victor L. J.
2012-01-01
The guanine nucleotide exchange factor (GEF) Vav1 is essential for transducing T cell antigen receptor (TCR) signals and therefore plays a critical role in the development and activation of T cells. It has been presumed that the GEF activity of Vav1 is important for its function; however, there has been no direct demonstration of this. Here, we generated mice expressing enzymatically inactive, but normally folded, Vav1 protein. Analysis of these mice showed that the GEF activity of Vav1 was necessary for the selection of thymocytes and for the optimal activation of T cells, including signal transduction to Rac1, Akt, and integrins. In contrast, the GEF activity of Vav1 was not required for TCR-induced calcium flux, activation of extracellular signal–regulated kinase (ERK) and protein kinase D1 (PKD1), and cell polarization. Thus, in T cells, the GEF activity of Vav1 is essential for some, but not all, of its functions. PMID:20009105
Espejo, Rosario; Jeng, Yowjiun; Paulucci-Holthauzen, Adriana; Rengifo-Cam, William; Honkus, Krysta; Anastasiadis, Panos Z; Sastry, Sarita K
2014-02-01
Tyrosine phosphorylation is implicated in regulating the adherens junction protein, p120 catenin (p120), however, the mechanisms are not well defined. Here, we show, using substrate trapping, that p120 is a direct target of the protein tyrosine phosphatase, PTP-PEST, in epithelial cells. Stable shRNA knockdown of PTP-PEST in colon carcinoma cells results in an increased cytosolic pool of p120 concomitant with its enhanced tyrosine phosphorylation and decreased association with E-cadherin. Consistent with this, PTP-PEST knockdown cells exhibit increased motility, enhanced Rac1 and decreased RhoA activity on a collagen substrate. Furthermore, p120 localization is enhanced at actin-rich protrusions and lamellipodia and has an increased association with the guanine nucleotide exchange factor, VAV2, and cortactin. Exchange factor activity of VAV2 is enhanced by PTP-PEST knockdown whereas overexpression of a VAV2 C-terminal domain or DH domain mutant blocks cell motility. Analysis of point mutations identified tyrosine 335 in the N-terminal domain of p120 as the site of PTP-PEST dephosphorylation. A Y335F mutant of p120 failed to induce the 'p120 phenotype', interact with VAV2, stimulate cell motility or activate Rac1. Together, these data suggest that PTP-PEST affects epithelial cell motility by controlling the distribution and phosphorylation of p120 and its availability to control Rho GTPase activity.
Espejo, Rosario; Jeng, Yowjiun; Paulucci-Holthauzen, Adriana; Rengifo-Cam, William; Honkus, Krysta; Anastasiadis, Panos Z.; Sastry, Sarita K.
2014-01-01
ABSTRACT Tyrosine phosphorylation is implicated in regulating the adherens junction protein, p120 catenin (p120), however, the mechanisms are not well defined. Here, we show, using substrate trapping, that p120 is a direct target of the protein tyrosine phosphatase, PTP-PEST, in epithelial cells. Stable shRNA knockdown of PTP-PEST in colon carcinoma cells results in an increased cytosolic pool of p120 concomitant with its enhanced tyrosine phosphorylation and decreased association with E-cadherin. Consistent with this, PTP-PEST knockdown cells exhibit increased motility, enhanced Rac1 and decreased RhoA activity on a collagen substrate. Furthermore, p120 localization is enhanced at actin-rich protrusions and lamellipodia and has an increased association with the guanine nucleotide exchange factor, VAV2, and cortactin. Exchange factor activity of VAV2 is enhanced by PTP-PEST knockdown whereas overexpression of a VAV2 C-terminal domain or DH domain mutant blocks cell motility. Analysis of point mutations identified tyrosine 335 in the N-terminal domain of p120 as the site of PTP-PEST dephosphorylation. A Y335F mutant of p120 failed to induce the ‘p120 phenotype’, interact with VAV2, stimulate cell motility or activate Rac1. Together, these data suggest that PTP-PEST affects epithelial cell motility by controlling the distribution and phosphorylation of p120 and its availability to control Rho GTPase activity. PMID:24284071
Chen, Chih-Hong; Piraner, Dan; Gorenstein, Nina M; Geahlen, Robert L; Beth Post, Carol
2013-11-01
The association of spleen tyrosine kinase (Syk), a central tyrosine kinase in B cell signaling, with Vav SH2 domain is controlled by phosphorylation of two closely spaced tyrosines in Syk linker B: Y342 and Y346. Previous studies established both singly phosphorylated and doubly phosphorylated forms play a role in signaling. The structure of the doubly phosphorylated form identified a new recognition of phosphotyrosine whereby two phosphotyrosines bind simultaneously to the Vav SH2 domain, one in the canonical pTyr pocket and one in the specificity pocket on the opposite side of the central β-sheet. It is unknown if the specificity pocket can bind phosphotyrosine independent of phosphotyrosine binding the pTyr pocket. To address this gap in knowledge, we determined the structure of the complex between Vav1 SH2 and a peptide (SykLB-YpY) modeling the singly phosphorylated-Y346 form of Syk with unphosphorylated Y342. The nuclear magnetic resonance (NMR) data conclusively establish that recognition of phosphotyrosine is swapped between the two pockets; phosphorylated pY346 binds the specificity pocket of Vav1 SH2, and unphosphorylated Y342 occupies what is normally the pTyr binding pocket. Nearly identical changes in chemical shifts occurred upon binding all three forms of singly and doubly phosphorylated peptides; however, somewhat smaller shift perturbations for SykLB-YpY from residues in regions of high internal mobility suggest that internal motions are coupled to binding affinity. The differential recognition that includes this swapped binding of phosphotyrosine to the specificity pocket of Vav SH2 increases the repertoire of possible phosphotyrosine binding by SH2 domains in regulating protein-protein interactions in cellular signaling. Copyright © 2013 Wiley Periodicals, Inc.
Cooperative interactions at the SLP-76 complex are critical for actin polymerization.
Barda-Saad, Mira; Shirasu, Naoto; Pauker, Maor H; Hassan, Nirit; Perl, Orly; Balbo, Andrea; Yamaguchi, Hiroshi; Houtman, Jon C D; Appella, Ettore; Schuck, Peter; Samelson, Lawrence E
2010-07-21
T-cell antigen receptor (TCR) engagement induces formation of multi-protein signalling complexes essential for regulating T-cell functions. Generation of a complex of SLP-76, Nck and VAV1 is crucial for regulation of the actin machinery. We define the composition, stoichiometry and specificity of interactions in the SLP-76, Nck and VAV1 complex. Our data reveal that this complex can contain one SLP-76 molecule, two Nck and two VAV1 molecules. A direct interaction between Nck and VAV1 is mediated by binding between the C-terminal SH3 domain of Nck and the VAV1 N-terminal SH3 domain. Disruption of the VAV1:Nck interaction deleteriously affected actin polymerization. These novel findings shed new light on the mechanism of actin polymerization after T-cell activation.
Targeting AR Variant-Coactivator Interactions to Exploit Prostate Cancer Vulnerabilities.
Magani, Fiorella; Peacock, Stephanie O; Rice, Meghan A; Martinez, Maria J; Greene, Ann M; Magani, Pablo S; Lyles, Rolando; Weitz, Jonathan R; Burnstein, Kerry L
2017-11-01
Castration-resistant prostate cancer (CRPC) progresses rapidly and is incurable. Constitutively active androgen receptor splice variants (AR-Vs) represent a well-established mechanism of therapeutic resistance and disease progression. These variants lack the AR ligand-binding domain and, as such, are not inhibited by androgen deprivation therapy (ADT), which is the standard systemic approach for advanced prostate cancer. Signaling by AR-Vs, including the clinically relevant AR-V7, is augmented by Vav3, an established AR coactivator in CRPC. Using mutational and biochemical studies, we demonstrated that the Vav3 Diffuse B-cell lymphoma homology (DH) domain interacted with the N-terminal region of AR-V7 (and full length AR). Expression of the Vav3 DH domain disrupted Vav3 interaction with and enhancement of AR-V7 activity. The Vav3 DH domain also disrupted AR-V7 interaction with other AR coactivators: Src1 and Vav2, which are overexpressed in PC. This Vav3 domain was used in proof-of-concept studies to evaluate the effects of disrupting the interaction between AR-V7 and its coactivators on CRPC cells. This disruption decreased CRPC cell proliferation and anchorage-independent growth, caused increased apoptosis, decreased migration, and resulted in the acquisition of morphological changes associated with a less aggressive phenotype. While disrupting the interaction between FL-AR and its coactivators decreased N-C terminal interaction, disrupting the interaction of AR-V7 with its coactivators decreased AR-V7 nuclear levels. Implications: This study demonstrates the potential therapeutic utility of inhibiting constitutively active AR-V signaling by disrupting coactivator binding. Such an approach is significant, as AR-Vs are emerging as important drivers of CRPC that are particularly recalcitrant to current therapies. Mol Cancer Res; 15(11); 1469-80. ©2017 AACR . ©2017 American Association for Cancer Research.
Lin, Kai-Yuan; Wang, Lu-Hai; Hseu, You-Cheng; Fang, Chia-Lang; Yang, Hsin-Ling; Kumar, K J Senthil; Tai, Chein; Uen, Yih-Huei
2012-06-01
Although gastric cancer is one of the most common malignancies worldwide, little is known on the molecular process of its development and progression. This study investigates the involvement of guanine nucleotide exchange factor Vav3 in tumor progression and in the prognosis of human gastric cancer. The two patient cohorts in this study consisted of 167 gastric cancer cases from 1997 through 2001, documenting pathologic and clinical factors, as well as the clinical outcomes. Immunohistochemistry, reverse transcription PCR, immunoblotting, and immunofluorescence were used to examine Vav3 expression in tumor and nontumor pairs of gastric tissues and gastric cell lines. Small hairpin RNA (shRNA) technology was used to study the effects of Vav3 knockdown on the growth and spread of gastric cancer cells. Finally, xenograph proliferation was used to study the tumor growth. Overexpression of Vav3 was associated with the depth of invasion (P = 0.0004), nodal status (P = 0.0260), distant metastasis (P = 0.0003), stage (P = 0.0002), and vascular invasion (P = 0.0286); and correlated with poor disease-free survival (P < 0.0001). Multivariate Cox regression analysis shows that overexpression of Vav3 is an independent prognostic marker for gastric cancer (P = 0.033). Disrupting the expression of Vav3 using shRNA technology inhibited gastric cancer cell growth, spread, and xenograph proliferation. This study suggests that overexpression of Vav3 can be a useful marker for predicting the outcome of patients with gastric cancer and that Vav3 targeting can represent a potential modality for treating gastric cancer. 2012 AACR
Mechanism and function of Vav1 localisation in TCR signalling
Ksionda, Olga; Saveliev, Alexander; Köchl, Robert; Rapley, Jonathan; Faroudi, Mustapha; Smith-Garvin, Jennifer E.; Wülfing, Christoph; Rittinger, Katrin; Carter, Tom; Tybulewicz, Victor L. J.
2012-01-01
Summary The antigen-specific binding of T cells to antigen presenting cells results in recruitment of signalling proteins to microclusters at the cell-cell interface known as the immunological synapse (IS). The Vav1 guanine nucleotide exchange factor plays a critical role in T cell antigen receptor (TCR) signalling, leading to the activation of multiple pathways. We now show that it is recruited to microclusters and to the IS in primary CD4+ and CD8+ T cells. Furthermore, we show that this recruitment depends on the SH2 and C-terminal SH3 (SH3B) domains of Vav1, and on phosphotyrosines 112 and 128 of the SLP76 adaptor protein. Biophysical measurements show that Vav1 binds directly to these residues on SLP76 and that efficient binding depends on the SH2 and SH3B domains of Vav1. Finally, we show that the same two domains are critical for the phosphorylation of Vav1 and its signalling function in TCR-induced calcium flux. We propose that Vav1 is recruited to the IS by binding to SLP76 and that this interaction is critical for the transduction of signals leading to calcium flux. PMID:22956543
Mechanism and function of Vav1 localisation in TCR signalling.
Ksionda, Olga; Saveliev, Alexander; Köchl, Robert; Rapley, Jonathan; Faroudi, Mustapha; Smith-Garvin, Jennifer E; Wülfing, Christoph; Rittinger, Katrin; Carter, Tom; Tybulewicz, Victor L J
2012-11-15
The antigen-specific binding of T cells to antigen presenting cells results in recruitment of signalling proteins to microclusters at the cell-cell interface known as the immunological synapse (IS). The Vav1 guanine nucleotide exchange factor plays a critical role in T cell antigen receptor (TCR) signalling, leading to the activation of multiple pathways. We now show that it is recruited to microclusters and to the IS in primary CD4(+) and CD8(+) T cells. Furthermore, we show that this recruitment depends on the SH2 and C-terminal SH3 (SH3(B)) domains of Vav1, and on phosphotyrosines 112 and 128 of the SLP76 adaptor protein. Biophysical measurements show that Vav1 binds directly to these residues on SLP76 and that efficient binding depends on the SH2 and SH3(B) domains of Vav1. Finally, we show that the same two domains are critical for the phosphorylation of Vav1 and its signalling function in TCR-induced calcium flux. We propose that Vav1 is recruited to the IS by binding to SLP76 and that this interaction is critical for the transduction of signals leading to calcium flux.
2017-03-01
FINAL REPORT Demonstration of Energy Savings in Commercial Buildings for Tiered Trim and Respond Method in Resetting Static Pressure for VAV...release Page Intentionally Left Blank This report was prepared under contract to the Department of Defense Environmental Security Technology...Certification Program (ESTCP). The publication of this report does not indicate endorsement by the Department of Defense, nor should the contents be
Minimum airflow reset of single-duct VAV terminal boxes
NASA Astrophysics Data System (ADS)
Cho, Young-Hum
Single duct Variable Air Volume (VAV) systems are currently the most widely used type of HVAC system in the United States. When installing such a system, it is critical to determine the minimum airflow set point of the terminal box, as an optimally selected set point will improve the level of thermal comfort and indoor air quality (IAQ) while at the same time lower overall energy costs. In principle, this minimum rate should be calculated according to the minimum ventilation requirement based on ASHRAE standard 62.1 and maximum heating load of the zone. Several factors must be carefully considered when calculating this minimum rate. Terminal boxes with conventional control sequences may result in occupant discomfort and energy waste. If the minimum rate of airflow is set too high, the AHUs will consume excess fan power, and the terminal boxes may cause significant simultaneous room heating and cooling. At the same time, a rate that is too low will result in poor air circulation and indoor air quality in the air-conditioned space. Currently, many scholars are investigating how to change the algorithm of the advanced VAV terminal box controller without retrofitting. Some of these controllers have been found to effectively improve thermal comfort, indoor air quality, and energy efficiency. However, minimum airflow set points have not yet been identified, nor has controller performance been verified in confirmed studies. In this study, control algorithms were developed that automatically identify and reset terminal box minimum airflow set points, thereby improving indoor air quality and thermal comfort levels, and reducing the overall rate of energy consumption. A theoretical analysis of the optimal minimum airflow and discharge air temperature was performed to identify the potential energy benefits of resetting the terminal box minimum airflow set points. Applicable control algorithms for calculating the ideal values for the minimum airflow reset were developed and applied to actual systems for performance validation. The results of the theoretical analysis, numeric simulations, and experiments show that the optimal control algorithms can automatically identify the minimum rate of heating airflow under actual working conditions. Improved control helps to stabilize room air temperatures. The vertical difference in the room air temperature was lower than the comfort value. Measurements of room CO2 levels indicate that when the minimum airflow set point was reduced it did not adversely affect the indoor air quality. According to the measured energy results, optimal control algorithms give a lower rate of reheating energy consumption than conventional controls.
VAV1 and BAFF, via NFκB pathway, are genetic risk factors for myasthenia gravis
Avidan, Nili; Le Panse, Rozen; Harbo, Hanne F; Bernasconi, Pia; Poulas, Konstantinos; Ginzburg, Elizabeta; Cavalcante, Paola; Colleoni, Lara; Baggi, Fulvio; Antozzi, Carlo; Truffault, Frédérique; Horn-Saban, Shirley; Pöschel, Simone; Zagoriti, Zoi; Maniaol, Angelina; Lie, Benedicte A; Bernard, Isabelle; Saoudi, Abdelhadi; Illes, Zsolt; Casasnovas Pons, Carlos; Melms, Arthur; Tzartos, Socrates; Willcox, Nicholas; Kostera-Pruszczyk, Anna; Tallaksen, Chantal; Mantegazza, Renato; Berrih-Aknin, Sonia; Miller, Ariel
2014-01-01
Objective To identify novel genetic loci that predispose to early-onset myasthenia gravis (EOMG) applying a two-stage association study, exploration, and replication strategy. Methods Thirty-four loci and one confirmation loci, human leukocyte antigen (HLA)-DRA, were selected as candidate genes by team members of groups involved in different research aspects of MG. In the exploration step, these candidate genes were genotyped in 384 EOMG and 384 matched controls and significant difference in allele frequency were found in eight genes. In the replication step, eight candidate genes and one confirmation loci were genotyped in 1177 EOMG patients and 814 controls, from nine European centres. Results Allele frequency differences were found in four novel loci: CD86, AKAP12, VAV1, B-cell activating factor (BAFF), and tumor necrosis factor-alpha (TNF-α), and these differences were consistent in all nine cohorts. Haplotype trend test supported the differences in allele frequencies between cases and controls. In addition, allele frequency difference in female versus male patients at HLA-DRA and TNF-α loci were observed. Interpretation The genetic associations to EOMG outside the HLA complex are novel and of interest as VAV1 is a key signal transducer essential for T- and B-cell activation, and BAFF is a cytokine that plays important roles in the proliferation and differentiation of B-cells. Moreover, we noted striking epistasis between the predisposing VAV1 and BAFF haplotypes; they conferred a greater risk in combination than alone. These, and CD86, share the same signaling pathway, namely nuclear factor-kappaB (NFκB), thus implicating dysregulation of proinflammatory signaling in predisposition to EOMG. PMID:25356403
Vav family exchange factors: an integrated regulatory and functional view
Bustelo, Xosé R
2014-01-01
The Vav family is a group of tyrosine phosphorylation-regulated signal transduction molecules hierarchically located downstream of protein tyrosine kinases. The main function of these proteins is to work as guanosine nucleotide exchange factors (GEFs) for members of the Rho GTPase family. In addition, they can exhibit a variety of catalysis-independent roles in specific signaling contexts. Vav proteins play essential signaling roles for both the development and/or effector functions of a large variety of cell lineages, including those belonging to the immune, nervous, and cardiovascular systems. They also contribute to pathological states such as cancer, immune-related dysfunctions, and atherosclerosis. Here, I will provide an integrated view about the evolution, regulation, and effector properties of these signaling molecules. In addition, I will discuss the pros and cons for their potential consideration as therapeutic targets. PMID:25483299
Users Guide to Direct Digital Control of Heating, Ventilating, and Air Conditioning Equipment,
1985-01-01
cycles, reset, load shedding, chiller optimization , VAV fan synchronization, and optimum start/stop. The prospective buyer of a DDC system should...in Fig- ure 4. Data on setpoints , reset schedules, and event timing, such as that presented in Figure 6, are often even more difficult to find. In con...control logic, setpoint and other data are readily available. Program logic, setpoint and schedule data, and other information stored in a DDC unit
Krishnan, Vyjayanthi; Andersen, Bo H.; Shoemaker, Christine; Sivko, Gloria S.; Tordoff, Kevin P.; Stark, Gregory V.; Zhang, Jianfeng; Feng, Tsungwei; Duchars, Matthew
2015-01-01
AdVAV is a replication-deficient adenovirus type 5-vectored vaccine expressing the 83-kDa protective antigen (PA83) from Bacillus anthracis that is being developed for the prevention of disease caused by inhalation of aerosolized B. anthracis spores. A noninferiority study comparing the efficacy of AdVAV to the currently licensed Anthrax Vaccine Absorbed (AVA; BioThrax) was performed in New Zealand White rabbits using postchallenge survival as the study endpoint (20% noninferiority margin for survival). Three groups of 32 rabbits were vaccinated with a single intranasal dose of AdVAV (7.5 × 107, 1.5 × 109, or 3.5 × 1010 viral particles). Three additional groups of 32 animals received two doses of either intranasal AdVAV (3.5 × 1010 viral particles) or intramuscular AVA (diluted 1:16 or 1:64) 28 days apart. The placebo group of 16 rabbits received a single intranasal dose of AdVAV formulation buffer. All animals were challenged via the inhalation route with a targeted dose of 200 times the 50% lethal dose (LD50) of aerosolized B. anthracis Ames spores 70 days after the initial vaccination and were followed for 3 weeks. PA83 immunogenicity was evaluated by validated toxin neutralizing antibody and serum anti-PA83 IgG enzyme-linked immunosorbent assays (ELISAs). All animals in the placebo cohort died from the challenge. Three of the four AdVAV dose cohorts tested, including two single-dose cohorts, achieved statistical noninferiority relative to the AVA comparator group, with survival rates between 97% and 100%. Vaccination with AdVAV also produced antibody titers with earlier onset and greater persistence than vaccination with AVA. PMID:25673303
David, Rachel; Ma, Liang; Ivetic, Aleksandar; Takesono, Aya; Ridley, Anne J.; Chai, Jian-Guo; Tybulewicz, Victor; Marelli-Berg, Federica M.
2016-01-01
Localization of primed T cells to antigenic tissue is essential for the development of effective immunity. Together with tissue-selective homing molecules, T-cell receptor (TCR)- and CD28-mediated signals have been shown to promote transendothelial migration of specific T cells into non-lymphoid antigen-rich tissue tissue. However, the cellular and molecular requirements for T-cell accumulation to target tissue following their recruitment are largely undefined. The guanine nucleotide exchange factor (GEF) Vav1 has an integral role in coupling TCR and CD28 to signalling pathways that regulate T cell activation and migration. Here, we have investigated the contribution of TCR- and CD28-induced Vav1 activity to the trafficking and localization of primed HY-specific CD4+ T cells to antigenic sites. Severe migratory defects displayed by Vav1-/- T cells in vitro were fully compensated by a combination of shear flow and chemokines, leading to normal recruitment of Vav1-/- T cells in vivo. In contrast, Vav1-/- T-cell retention into antigen-rich tissue was severely impaired, reflecting their inability to engage in sustained TCR- and CD28-mediated interactions with tissue-resident antigen-presenting cells (APCs). This novel function of APC-induced, TCR- and CD28-mediated Vav1 activity in the regulation of effector T-cell immunity highlights its potential as a therapeutic target in T-cell-mediated tissue damage. PMID:19060239
Pak and Rac GTPases promote oncogenic KIT–induced neoplasms
Martin, Holly; Mali, Raghuveer Singh; Ma, Peilin; Chatterjee, Anindya; Ramdas, Baskar; Sims, Emily; Munugalavadla, Veerendra; Ghosh, Joydeep; Mattingly, Ray R.; Visconte, Valeria; Tiu, Ramon V.; Vlaar, Cornelis P.; Dharmawardhane, Suranganie; Kapur, Reuben
2013-01-01
An acquired somatic mutation at codon 816 in the KIT receptor tyrosine kinase is associated with poor prognosis in patients with systemic mastocytosis and acute myeloid leukemia (AML). Treatment of leukemic cells bearing this mutation with an allosteric inhibitor of p21–activated kinase (Pak) or its genetic inactivation results in growth repression due to enhanced apoptosis. Inhibition of the upstream effector Rac abrogates the oncogene-induced growth and activity of Pak. Although both Rac1 and Rac2 are constitutively activated via the guanine nucleotide exchange factor (GEF) Vav1, loss of Rac1 or Rac2 alone moderately corrected the growth of KIT-bearing leukemic cells, whereas the combined loss resulted in 75% growth repression. In vivo, the inhibition of Vav or Rac or Pak delayed the onset of myeloproliferative neoplasms (MPNs) and corrected the associated pathology in mice. To assess the role of Rac GEFs in oncogene-induced transformation, we used an inhibitor of Rac, EHop-016, which specifically targets Vav1 and found that EHop-016 was a potent inhibitor of human and murine leukemic cell growth. These studies identify Pak and Rac GTPases, including Vav1, as potential therapeutic targets in MPN and AML involving an oncogenic form of KIT. PMID:24091327
Bariana, H. S.; Brown, G. N.; Ahmed, N. U.; Khatkar, S.; Conner, R. L.; Wellings, C. R.; Haley, S.; Sharp, P. J.; Laroche, A.
2002-02-01
Stripe rust resistance was identified in Triticum vavilovii( T. vaviloviiAus22498)-derived Russian wheat aphid (RWA)-resistant germplasm. Inheritance studies indicated monogenic control of resistance. The resistance gene was tentatively designated as Yrvav and was located on chromosome 1B by monosomic analysis. A close association (1.5+/-0.9% recombination) of Yrvav with a T. vavilovii-derived gliadin allele ( Gli-B1vav) placed it in chromosome arm 1BS. Yrvavwas allelic with Yr10. Tests with Yr10 avirulent and virulent pathotypes showed that Yrvav and Yr10 possess identical pathogenic specificity. Yrvav and Yr10 showed close genetic associations with alternate alleles at the Xpsp3000(microsatellite marker), Gli-B1 and Rg1 loci. Based on these observations Yrvav was named as Yr10vav. The close association between Xpsp3000 and Gli-B1 was also confirmed. The Yr10vav-linked Xpsp3000 allele (285 bp) was not present in 65 Australian cultivars, whereas seven Australian wheats lacking Yr10 carried the same Xpsp3000 allele (260 bp) as Yr10carrying wheat cultivar Moro. Xpsp3000 and/or Gli-B1 could be used in marker-assisted selection for pyramiding Yr10vavor Yr10 with other stripe rust resistance genes. Yr10vav was inherited independently of the T. vavilovii-derived RWA resistance.
Vav1: Friend and Foe of Cancer.
Guo, Fukun; Zheng, Yi
2017-12-01
A recent study shows that the protumorigenic guanine nucleotide exchange factor (GEF) Vav1 functions as a tumor suppressor in T cell acute lymphoblastic leukemia (T-ALL) through its ability to complex with the Cbl-b ubiquitin ligase and the intracellular domain of Notch1 (ICN1) and to promote ICN1 degradation. Vav1can act as a double-edged sword in tumorigenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.
Krishnan, Vyjayanthi; Andersen, Bo H; Shoemaker, Christine; Sivko, Gloria S; Tordoff, Kevin P; Stark, Gregory V; Zhang, Jianfeng; Feng, Tsungwei; Duchars, Matthew; Roberts, M Scot
2015-04-01
AdVAV is a replication-deficient adenovirus type 5-vectored vaccine expressing the 83-kDa protective antigen (PA83) from Bacillus anthracis that is being developed for the prevention of disease caused by inhalation of aerosolized B. anthracis spores. A noninferiority study comparing the efficacy of AdVAV to the currently licensed Anthrax Vaccine Absorbed (AVA; BioThrax) was performed in New Zealand White rabbits using postchallenge survival as the study endpoint (20% noninferiority margin for survival). Three groups of 32 rabbits were vaccinated with a single intranasal dose of AdVAV (7.5 × 10(7), 1.5 × 10(9), or 3.5 × 10(10) viral particles). Three additional groups of 32 animals received two doses of either intranasal AdVAV (3.5 × 10(10) viral particles) or intramuscular AVA (diluted 1:16 or 1:64) 28 days apart. The placebo group of 16 rabbits received a single intranasal dose of AdVAV formulation buffer. All animals were challenged via the inhalation route with a targeted dose of 200 times the 50% lethal dose (LD50) of aerosolized B. anthracis Ames spores 70 days after the initial vaccination and were followed for 3 weeks. PA83 immunogenicity was evaluated by validated toxin neutralizing antibody and serum anti-PA83 IgG enzyme-linked immunosorbent assays (ELISAs). All animals in the placebo cohort died from the challenge. Three of the four AdVAV dose cohorts tested, including two single-dose cohorts, achieved statistical noninferiority relative to the AVA comparator group, with survival rates between 97% and 100%. Vaccination with AdVAV also produced antibody titers with earlier onset and greater persistence than vaccination with AVA. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
NASA Astrophysics Data System (ADS)
Spasis, Georgios
The increasing demand for air conditioning in commercial buildings imposes a serious threat to Europe's CO2 reduction targets. Architects and engineers are therefore in a key position to help reduce the impact of buildings on the environment by taking appropriate decisions concerning the design of the building and the associated heating, ventilation and air conditioning (HVAC) system. The thesis studies the effect of a number of building and HVAC system related design factors on the energy performance of a notional air-conditioned office building employing either a variable air volume (VAV) system with terminal re-heaters, or a four-pipe fan coil unit (FCU) system with fresh air supply from a central plant, using mainly a dynamic simulation tool and the response surface methodology. The evaluation of the energy performance of the HVAC systems is for two types of climate, using typical weather data for London (UK) and Athens (Greece). It has been found that the design variables associated with the solar radiation through the transparent building elements and the internal heat gains should be the main concern of the building designer. On the other hand, the HVAC system engineer should give emphasis to the parameters associated with the plant performance and operation, as well as the temperature control set-points. It has been shown that it is possible to reduce the carbon emissions of the base case scenario by up to 88% depending on the HVAC system and the climate for which it is simulated. The carbon savings, however, are reduced by up to 22% where humidification is provided. This reduction differs depending on the HVAC system and the climatic conditions. The VAV system is more energy efficient than the FCU system, mainly due to the exploitation of the free cooling capacity of the outdoor air. The difference in carbon emissions between the two systems drops when both of them are simulated for the Athens as opposed to the London typical weather conditions. It has been found that it is possible to turn the carbon scales in favour of the FCU system when humidification to a high RH set-point is provided throughout the year, since the adjustment of the RH of the air is particularly energy wasteful for the VAV system.
Almarza, Elena; Río, Paula; Meza, Nestor W; Aldea, Montserrat; Agirre, Xabier; Guenechea, Guillermo; Segovia, José C; Bueren, Juan A
2007-08-01
Recent published data have shown the efficacy of gene therapy treatments of certain monogenic diseases. Risks of insertional oncogenesis, however, indicate the necessity of developing new vectors with weaker or cell-restricted promoters to minimize the trans-activation activity of integrated proviruses. We have inserted the proximal promoter of the vav proto-oncogene into self-inactivating lentiviral vectors (vav-LVs) and investigated the expression pattern and therapeutic efficacy of these vectors. Compared with other LVs frequently used in gene therapy, vav-LVs mediated a weak, though homogeneous and stable, expression in in vitro-cultured cells. Transplantation experiments using transduced mouse bone marrow and human CD34(+) cells confirmed the stable activity of the promoter in vivo. To investigate whether the weak activity of this promoter was compatible with a therapeutic effect, a LV expressing the Fanconi anemia A (FANCA) gene was constructed (vav-FANCA LV). Although this vector induced a low expression of FANCA, compared to the expression induced by a LV harboring the spleen focus-forming virus (SFFV) promoter, the two vectors corrected the phenotype of cells from a patient with FA-A with the same efficacy. We propose that self-inactivating vectors harboring weak promoters, such as the vav promoter, will improve the safety of gene therapy and will be of particular interest for the treatment of diseases where a high expression of the transgene is not required.
ANSI Standard: Complying with Background Noise Limits.
ERIC Educational Resources Information Center
Schaffer, Mark E.
2003-01-01
Discusses the new classroom acoustics standard, ANSI Standard S12.60, which specifies maximum sound level limits that are significantly lower than currently typical for classrooms. Addresses guidelines for unducted HVAC systems, ducted single-zone systems, and central VAV or multizone systems. (EV)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tian, Wei; Sevilla, Thomas Alonso; Zuo, Wangda
Historically, multizone models are widely used in building airflow and energy performance simulations due to their fast computing speed. However, multizone models assume that the air in a room is well mixed, consequently limiting their application. In specific rooms where this assumption fails, the use of computational fluid dynamics (CFD) models may be an alternative option. Previous research has mainly focused on coupling CFD models and multizone models to study airflow in large spaces. While significant, most of these analyses did not consider the coupled simulation of the building airflow with the building's Heating, Ventilation, and Air-Conditioning (HVAC) systems. Thismore » paper tries to fill the gap by integrating the models for HVAC systems with coupled multizone and CFD simulations for airflows, using the Modelica simul ation platform. To improve the computational efficiency, we incorporated a simplified CFD model named fast fluid dynamics (FFD). We first introduce the data synchronization strategy and implementation in Modelica. Then, we verify the implementation using two case studies involving an isothermal and a non-isothermal flow by comparing model simulations to experiment data. Afterward, we study another three cases that are deemed more realistic. This is done by attaching a variable air volume (VAV) terminal box and a VAV system to previous flows to assess the capability of the models in studying the dynamic control of HVAC systems. Finally, we discuss further research needs on the coupled simulation using the models.« less
2014-01-01
Background Polycystic ovarian syndrome (PCOS) is characterized by the presence of multiple follicular cysts, giving rise to infertility due to anovulation. This syndrome affects about 10% of women, worldwide. The exact molecular mechanism leading to PCOS remains obscure. RhoGTPase has been associated with oogenesis, but its role in PCOS remains unexplored. Therefore, we attempted to elucidate the Vav-Rac1 signaling in PCOS mice model. Methods We generated a PCOS mice model by injecting dehydroepiandrosterone (DHEA) for a period of 20 days. The expression levels of Rac1, pRac1, Vav, pVav and Caveolin1 were analyzed by employing immuno-blotting and densitometry. The association between Vav and Rac1 proteins were studied by immuno-precipitation. Furthermore, we analyzed the activity of Rac1 and levels of inhibin B and 17β-estradiol in ovary using biochemical assays. Results The presence of multiple follicular cysts in ovary were confirmed by histology. The activity of Rac1 (GTP bound state) was significantly reduced in the PCOS ovary. Similarly, the expression levels of Rac1 and its phosphorylated form (pRac1) were decreased in PCOS in comparison to the sham ovary. The expression level and activity (phosphorylated form) of guanine nucleotide exchanger of Rac1, Vav, was moderately down-regulated. We observed comparatively increased expressions of Caveolin1, 17β-estradiol, and inhibin B in the polycystic ovary. Conclusion We conclude that hyperandrogenization (PCOS) by DHEA diminishes ovarian Rac1 and Vav expression and activity along with an increase in expression of Caveolin1. This is accompanied by an increase in the intra-ovarian level of '17 β-estradiol and inhibin B. PMID:24628852
Phage display discovery of novel molecular targets in glioblastoma-initiating cells.
Liu, J K; Lubelski, D; Schonberg, D L; Wu, Q; Hale, J S; Flavahan, W A; Mulkearns-Hubert, E E; Man, J; Hjelmeland, A B; Yu, J; Lathia, J D; Rich, J N
2014-08-01
Glioblastoma is the most common primary intrinsic brain tumor and remains incurable despite maximal therapy. Glioblastomas display cellular hierarchies with self-renewing glioma-initiating cells (GICs) at the apex. To discover new GIC targets, we used in vivo delivery of phage display technology to screen for molecules selectively binding GICs that may be amenable for targeting. Phage display leverages large, diverse peptide libraries to identify interactions with molecules in their native conformation. We delivered a bacteriophage peptide library intravenously to a glioblastoma xenograft in vivo then derived GICs. Phage peptides bound to GICs were analyzed for their corresponding proteins and ranked based on prognostic value, identifying VAV3, a Rho guanine exchange factor involved tumor invasion, and CD97 (cluster of differentiation marker 97), an adhesion G-protein-coupled-receptor upstream of Rho, as potentially enriched in GICs. We confirmed that both VAV3 and CD97 were preferentially expressed by tumor cells expressing GIC markers. VAV3 expression correlated with increased activity of its downstream mediator, Rac1 (ras-related C3 botulinum toxin substrate 1), in GICs. Furthermore, targeting VAV3 by ribonucleic acid interference decreased GIC growth, migration, invasion and in vivo tumorigenesis. As CD97 is a cell surface protein, CD97 selection enriched for sphere formation, a surrogate of self-renewal. In silico analysis demonstrated VAV3 and CD97 are highly expressed in tumors and inform poor survival and tumor grade, and more common with epidermal growth factor receptor mutations. Finally, a VAV3 peptide sequence identified on phage display specifically internalized into GICs. These results show a novel screening method for identifying oncogenic pathways preferentially activated within the tumor hierarchy, offering a new strategy for developing glioblastoma therapies.
Phage display discovery of novel molecular targets in glioblastoma-initiating cells
Liu, J K; Lubelski, D; Schonberg, D L; Wu, Q; Hale, J S; Flavahan, W A; Mulkearns-Hubert, E E; Man, J; Hjelmeland, A B; Yu, J; Lathia, J D; Rich, J N
2014-01-01
Glioblastoma is the most common primary intrinsic brain tumor and remains incurable despite maximal therapy. Glioblastomas display cellular hierarchies with self-renewing glioma-initiating cells (GICs) at the apex. To discover new GIC targets, we used in vivo delivery of phage display technology to screen for molecules selectively binding GICs that may be amenable for targeting. Phage display leverages large, diverse peptide libraries to identify interactions with molecules in their native conformation. We delivered a bacteriophage peptide library intravenously to a glioblastoma xenograft in vivo then derived GICs. Phage peptides bound to GICs were analyzed for their corresponding proteins and ranked based on prognostic value, identifying VAV3, a Rho guanine exchange factor involved tumor invasion, and CD97 (cluster of differentiation marker 97), an adhesion G-protein-coupled-receptor upstream of Rho, as potentially enriched in GICs. We confirmed that both VAV3 and CD97 were preferentially expressed by tumor cells expressing GIC markers. VAV3 expression correlated with increased activity of its downstream mediator, Rac1 (ras-related C3 botulinum toxin substrate 1), in GICs. Furthermore, targeting VAV3 by ribonucleic acid interference decreased GIC growth, migration, invasion and in vivo tumorigenesis. As CD97 is a cell surface protein, CD97 selection enriched for sphere formation, a surrogate of self-renewal. In silico analysis demonstrated VAV3 and CD97 are highly expressed in tumors and inform poor survival and tumor grade, and more common with epidermal growth factor receptor mutations. Finally, a VAV3 peptide sequence identified on phage display specifically internalized into GICs. These results show a novel screening method for identifying oncogenic pathways preferentially activated within the tumor hierarchy, offering a new strategy for developing glioblastoma therapies. PMID:24832468
Developmentally induced Mll1 loss reveals defects in postnatal haematopoiesis.
Gan, T; Jude, C D; Zaffuto, K; Ernst, P
2010-10-01
The mixed lineage leukemia (MLL) gene is disrupted by chromosomal translocations in acute leukemia, producing a fusion oncogene with altered properties relative to the wild-type gene. Murine loss-of-function studies have shown an essential role for Mll in developing the haematopoietic system, yet studies using different conditional knockout models have yielded conflicting results regarding the requirement for Mll during adult steady-state haematopoiesis. In this study, we used a loxP-flanked Mll allele (Mll(F)) and a developmentally regulated, haematopoietic-specific VavCre transgene to reassess the consequences of Mll loss in the haematopoietic lineage, without the need for inducers of Cre recombinase. We show that VavCre;Mll mutants exhibit phenotypically normal fetal haematopoiesis, but rarely survive past 3 weeks of age. Surviving animals are anemic, thrombocytopenic and exhibit a significant reduction in bone marrow haematopoietic stem/progenitor populations, consistent with our previous findings using the inducible Mx1Cre transgene. Furthermore, the analysis of VavCre mutants revealed additional defects in B-lymphopoiesis that could not be assessed using Mx1Cre-mediated Mll deletion. Collectively, these data support the conclusion that Mll has an essential role in sustaining postnatal haematopoiesis.
Candidate Socioemotional Remediation Program for Individuals with Intellectual Disability
ERIC Educational Resources Information Center
Glaser, Bronwyn; Lothe, Amelie; Chabloz, Melanie; Dukes, Daniel; Pasca, Catherine; Redoute, Jerome; Eliez, Stephan
2012-01-01
The authors developed a computerized program, Vis-a-Vis (VAV), to improve socioemotional functioning and working memory in children with developmental disabilities. The authors subsequently tested whether participants showed signs of improving the targeted skills. VAV is composed of three modules: Focus on the Eyes, Emotion Recognition and…
The Analysis for Energy Consumption of Marine Air Conditioning System Based on VAV and VWV
NASA Astrophysics Data System (ADS)
Xu, Sai Feng; Yang, Xing Lin; Le, Zou Ying
2018-06-01
For ocean-going vessels sailing in different areas on the sea, the change of external environment factors will cause frequent changes in load, traditional ship air-conditioning system is usually designed with a fixed cooling capacity, this design method causes serious waste of resources. A new type of sea-based air conditioning system is proposed in this paper, which uses the sea-based source heat pump system, combined with variable air volume, variable water technology. The multifunctional cabins' dynamic loads for a ship navigating in a typical Eurasian route were calculated based on Simulink. The model can predict changes in full voyage load. Based on the simulation model, the effects of variable air volume and variable water volume on the energy consumption of the air-conditioning system are analyzed. The results show that: When the VAV is coupled with the VWV, the energy saving rate is 23.2%. Therefore, the application of variable air volume and variable water technology to marine air conditioning systems can achieve economical and energy saving advantages.
Performance assessment of a photonic radiative cooling system for office buildings
Wang, Weimin; Fernandez, Nick; Katipamula, Srinivas; ...
2017-11-08
Recent advances in materials have demonstrated the ability to maintain radiator surfaces at below-ambient temperatures in the presence of intense, direct sunlight. Daytime radiative cooling is promising for building applications. Here, this paper estimates the energy savings from daytime radiative cooling, specifically based on photonic materials. A photonic radiative cooling system was proposed and modeled using the whole energy simulation program EnergyPlus. A typical medium-sized office building was used for the simulation analysis. Several reference systems were established to quantify the potential of energy savings from the photonic radiative cooling system. The reference systems include a variable-air-volume (VAV) system, amore » hydronic radiant system, and a nighttime radiative cooling system. The savings analysis was made for a number of locations with different climates. Simulation results showed that the photonic radiative cooling system saved between 45% and 68% cooling electricity relative to the VAV system and between 9% and 23% relative to the nighttime radiative cooling system featured with the best coating commercially available on market. Finally, a simple economic analysis was also made to estimate the maximum acceptable incremental cost for upgrading from nighttime cooling to photonic radiative cooling.« less
Performance assessment of a photonic radiative cooling system for office buildings
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Weimin; Fernandez, Nick; Katipamula, Srinivas
Recent advances in materials have demonstrated the ability to maintain radiator surfaces at below-ambient temperatures in the presence of intense, direct sunlight. Daytime radiative cooling is promising for building applications. Here, this paper estimates the energy savings from daytime radiative cooling, specifically based on photonic materials. A photonic radiative cooling system was proposed and modeled using the whole energy simulation program EnergyPlus. A typical medium-sized office building was used for the simulation analysis. Several reference systems were established to quantify the potential of energy savings from the photonic radiative cooling system. The reference systems include a variable-air-volume (VAV) system, amore » hydronic radiant system, and a nighttime radiative cooling system. The savings analysis was made for a number of locations with different climates. Simulation results showed that the photonic radiative cooling system saved between 45% and 68% cooling electricity relative to the VAV system and between 9% and 23% relative to the nighttime radiative cooling system featured with the best coating commercially available on market. Finally, a simple economic analysis was also made to estimate the maximum acceptable incremental cost for upgrading from nighttime cooling to photonic radiative cooling.« less
Assessment of the Activation of Rho Family GTP-Binding Proteins in Breast Cancer Cells and Specimens
2001-08-01
lymphopenia Vav2 GEF for Rho, Rac, and Cdc42 proto-oncogene product; NM009500 Vav3 GEF for Rho and Rac proto-oncogene product; NM020505 hPEM -2 GEF for...junctions, and desmosomes play a fundamental role in maintaining the polarized phenotype and vectorial transport functions of epithelial cells. The tight
Yin, Shanshan; Zhang, Jianmin; Mao, Yujia; Hu, Yu; Cui, Lianxian; Kang, Ning; He, Wei
2013-09-13
T cell antigen receptor γδ (TCRγδ) and natural killer group 2, member D (NKG2D) are two crucial receptors for γδT cell cytotoxicity. Compelling evidences suggest that γδT cell cytotoxicity is TCRγδ-dependent and can be co-stimulated by NKG2D. However, the molecular mechanism of underlying TCRγδ-dependent activation of γδT cells remains unclear. In this study we demonstrated that TCRγδ but not NKG2D engagement induced lytic granule polarization and promoted γδT cell cytotoxicity. TCRγδ activation alone was sufficient to trigger Vav1-dependent phospholipase C-γ1 signaling, resulting in lytic granule polarization and effective killing, whereas NKG2D engagement alone failed to trigger cytotoxicity-related signaling to overcome the inhibitory effect of Cbl-b; therefore, NKG2D engagement alone could not induce effective killing. However, NKG2D ligation augmented the activation of γδT cell cytotoxicity through the Vav1-phospholipase C-γ1 pathway. Vav1 overexpression or Cbl-b knockdown not only enhanced TCRγδ activation-initiated killing but also enabled NKG2D activation alone to induce γδT cell cytotoxicity. Taken together, our results suggest that the activation of γδT cell cytotoxicity requires a strong activation signal to overcome the inhibitory effect of Cbl-b. Our finding provides new insights into the molecular mechanisms underlying the initiation of γδT cell cytotoxicity and likely implications for optimizing γδT cell-based cancer immunotherapy.
Nomura, Takeo; Yamasaki, Mutsushi; Mimata, Hiromitsu
2014-12-01
Cancer cells encounter a hypoxic microenvironment during tumor growth and progression. In addition, androgen-deprivation therapy against prostate cancer can develop secondary to a hypoxic condition caused by drastic blood supply reduction because androgen drives angiogenic inducers including vascular endothelial growth factor (VEGF) and inhibits angiogenesis inhibitor prostatic pigment epithelium-derived factor (PEDF). Extreme hypoxic conditions are not suitable for cancer survival, however, cancer cells soon adapt to a hypoxic environment and survive. We established a prostate cancer cell line cultured under chronic hypoxia and analyzed a castration-resistant phenotype. Here, the Vav3 was identified as a key oncogenic molecule associated with castration-resistance under chronic hypoxia. We analyzed the functions of Vav3 and Vav3-mediated signaling to establish a novel therapeutic target for castration-resistant prostate cancer.
2011-01-01
Background Host cell invasion by the foodborne pathogen Campylobacter jejuni is considered as one of the primary reasons of gut tissue damage, however, mechanisms and key factors involved in this process are widely unclear. It was reported that small Rho GTPases, including Cdc42, are activated and play a role during invasion, but the involved signaling cascades remained unknown. Here we utilised knockout cell lines derived from fibronectin-/-, integrin-beta1-/-, focal adhesion kinase (FAK)-/- and Src/Yes/Fyn-/- deficient mice, and wild-type control cells, to investigate C. jejuni-induced mechanisms leading to Cdc42 activation and bacterial uptake. Results Using high-resolution scanning electron microscopy, GTPase pulldowns, G-Lisa and gentamicin protection assays we found that each studied host factor is necessary for induction of Cdc42-GTP and efficient invasion. Interestingly, filopodia formation and associated membrane dynamics linked to invasion were only seen during infection of wild-type but not in knockout cells. Infection of cells stably expressing integrin-beta1 variants with well-known defects in fibronectin fibril formation or FAK signaling also exhibited severe deficiencies in Cdc42 activation and bacterial invasion. We further demonstrated that infection of wild-type cells induces increasing amounts of phosphorylated FAK and growth factor receptors (EGFR and PDGFR) during the course of infection, correlating with accumulating Cdc42-GTP levels and C. jejuni invasion over time. In studies using pharmacological inhibitors, silencing RNA (siRNA) and dominant-negative expression constructs, EGFR, PDGFR and PI3-kinase appeared to represent other crucial components upstream of Cdc42 and invasion. siRNA and the use of Vav1/2-/- knockout cells further showed that the guanine exchange factor Vav2 is required for Cdc42 activation and maximal bacterial invasion. Overexpression of certain mutant constructs indicated that Vav2 is a linker molecule between Cdc42 and activated EGFR/PDGFR/PI3-kinase. Using C. jejuni mutant strains we further demonstrated that the fibronectin-binding protein CadF and intact flagella are involved in Cdc42-GTP induction, indicating that the bacteria may directly target the fibronectin/integrin complex for inducing signaling leading to its host cell entry. Conclusion Collectively, our findings led us propose that C. jejuni infection triggers a novel fibronectin→integrin-beta1→FAK/Src→EGFR/PDGFR→PI3-kinase→Vav2 signaling cascade, which plays a crucial role for Cdc42 GTPase activity associated with filopodia formation and enhances bacterial invasion. PMID:22204307
A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus
Alejo, Alí; Ruiz-Argüello, M. Begoña; Ho, Yin; Smith, Vincent P.; Saraiva, Margarida; Alcami, Antonio
2006-01-01
Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis. PMID:16581912
A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus.
Alejo, Alí; Ruiz-Argüello, M Begoña; Ho, Yin; Smith, Vincent P; Saraiva, Margarida; Alcami, Antonio
2006-04-11
Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis.
Kinematic Modeling of Normal Voluntary Mandibular Opening and Closing Velocity-Initial Study.
Gawriołek, Krzysztof; Gawriołek, Maria; Komosa, Marek; Piotrowski, Paweł R; Azer, Shereen S
2015-06-01
Determination and quantification of voluntary mandibular velocity movement has not been a thoroughly studied parameter of masticatory movement. This study attempted to objectively define kinematics of mandibular movement based on numerical (digital) analysis of the relations and interactions of velocity diagram records in healthy female individuals. Using a computerized mandibular scanner (K7 Evaluation Software), 72 diagrams of voluntary mandibular velocity movements (36 for opening, 36 for closing) for women with clinically normal motor and functional activities of the masticatory system were recorded. Multiple measurements were analyzed focusing on the curve for maximum velocity records. For each movement, the loop of temporary velocities was determined. The diagram was then entered into AutoCad calculation software where movement analysis was performed. The real maximum velocity values on opening (Vmax ), closing (V0 ), and average velocity values (Vav ) as well as movement accelerations (a) were recorded. Additionally, functional (A1-A2) and geometric (P1-P4) analysis of loop constituent phases were performed, and the relations between the obtained areas were defined. Velocity means and correlation coefficient values for various velocity phases were calculated. The Wilcoxon test produced the following maximum and average velocity results: Vmax = 394 ± 102, Vav = 222 ± 61 for opening, and Vmax = 409 ± 94, Vav = 225 ± 55 mm/s for closing. Both mandibular movement range and velocity change showed significant variability achieving the highest velocity in P2 phase. Voluntary mandibular velocity presents significant variations between healthy individuals. Maximum velocity is obtained when incisal separation is between 12.8 and 13.5 mm. An improved understanding of the patterns of normal mandibular movements may provide an invaluable diagnostic aid to pathological changes within the masticatory system. © 2014 by the American College of Prosthodontists.
Distinct mechanisms of a phosphotyrosyl peptide binding to two SH2 domains.
Pang, Xiaodong; Zhou, Huan-Xiang
2014-05-01
Protein phosphorylation is very common post-translational modification, catalyzed by kinases, for signaling and regulation. Phosphotyrosines frequently target SH2 domains. The spleen tyrosine kinase (Syk) is critical for tyrosine phosphorylation of multiple proteins and for regulation of important pathways. Phosphorylation of both Y342 and Y346 in Syk linker B is required for optimal signaling. The SH2 domains of Vav1 and PLC-γ both bind this doubly phosphorylated motif. Here we used a recently developed method to calculate the effects of Y342 and Y346 phosphorylation on the rate constants of a peptide from Syk linker B binding to the SH2 domains of Vav1 and PLC-γ. The predicted effects agree well with experimental observations. Moreover, we found that the same doubly phosphorylated peptide binds the two SH2 domains via distinct mechanisms, with apparent rigid docking for Vav1 SH2 and dock-and-coalesce for PLC-γ SH2.
Association Between Visceral Adiposity and Colorectal Polyps on CT Colonography
Summers, Ronald M.; Liu, Jiamin; Sussman, Daniel L.; Dwyer, Andrew J.; Rehani, Bhavya; Pickhardt, Perry J.; Choi, J. Richard; Yao, Jianhua
2012-01-01
OBJECTIVE To determine if there is an association between visceral adiposity measured on CT colonography (CTC) and colorectal polyps. MATERIALS AND METHODS The study was HIPAA-compliant and approved by our Institutional Review Board and Office of Human Subjects Research. 1186 patients who underwent CTC and same day optical colonoscopy were analyzed. Visceral adipose tissue volumes (VAV) and volume percents relative to total internal body volume (VAV%) were measured on slices in the L2–L3 regions on supine CTC scan with validated fully-automated software. Student t-test, odds ratio (OR), logistic regression and receiver operating characteristic analyses were performed. RESULTS For subjects with and without adenomatous polyps, means and s. d. of VAV% were 31.2 ± 10.8% (n=345) and 28.2% ± 11.3% (n=841) (p<0.0001), respectively. For subjects with and without hyperplastic polyps they were 31.8% ± 10.7% (n=244) and 28.3% ± 11.2% (n=942) (p<0.0001), respectively. Comparing the lowest and highest quintiles of VAV%, the ORs for having at least one adenomatous polyp or hyperplastic polyp versus no polyp were 2.06 (95% CI: 1.36–3.13) and 1.71 [1.08, 2.71] and the prevalence of having adenomatous polyps or hyperplastic polyps increased 14% and 8%, respectively. CONCLUSION Subjects with higher visceral adiposity measurements on CTC have a greater risk for the presence of colonic polyps. PMID:22733893
SLP-76 couples Syk to the osteoclast cytoskeleton.
Reeve, Jennifer L; Zou, Wei; Liu, Yuli; Maltzman, Jonathan S; Ross, F Patrick; Teitelbaum, Steven L
2009-08-01
The capacity of the osteoclast (OC) to resorb bone is dictated by cytoskeletal organization, which in turn emanates from signals derived from the alpha(v)beta(3) integrin and c-Fms. Syk is key to these signals and, in other cells, this tyrosine kinase exerts its effects via intermediaries including the SLP adaptors, SLP-76 and BLNK (B cell linker). Thus, we asked whether these two SLP proteins regulate OC function. We find BLNK-deficient OCs are normal, whereas cytoskeletal organization of those lacking SLP-76 is delayed, thus modestly reducing bone resorption in vitro. Cytoskeletal organization and bone resorption are more profoundly arrested in cultured OCs deficient in BLNK and SLP-76 double knockout (DKO) phenotypes. In contrast, stimulated bone resorption in vivo is inhibited approximately 40% in either SLP-76(-/-) or DKO mice. This observation, taken with the fact that DKO OCs are rescued by retroviral transduction of only SLP-76, indicates that SLP-76 is the dominant SLP family member in the resorptive process. We also find SLP-76 is phosphorylated in a Syk-dependent manner. Furthermore, in the absence of the adaptor protein, integrin-mediated phosphorylation of Vav3, the OC cytoskeleton-organizing guanine nucleotide exchange factor, is abrogated. In keeping with a central role of SLP-76/Vav3 association in osteoclastic resorption, retroviral transduction of SLP-76, in which the Vav binding site is disrupted (3YF), fails to normalize the cytoskeleton of DKO OCs and the resorptive capacity of the cells. Finally, c-Fms-activated Syk also exerts its OC cytoskeleton-organizing effect in a SLP-76/Vav3-dependent manner.
Manes, Thomas D.; Pober, Jordan S.
2013-01-01
Human effector memory (EM) CD4 T cells may be recruited from the blood into a site of inflammation in response either to inflammatory chemokines displayed on or specific antigen presented by venular endothelial cells (ECs), designated as chemokine-driven or TCR-driven transendothelial migration (TEM), respectively. We have previously described differences in the morphological appearance of transmigrating T cells as well as in the molecules that mediate T cell-EC interactions distinguishing these two pathways. Here we report that TCR-driven TEM requires ZAP-70-dependent activation of a pathway involving Vav, Rac and myosin IIA. Chemokine-driven TEM also utilizes ZAP-70, albeit in a quantitatively and spatially different manner of activation, and is independent of Vav, Rac and mysosin IIA, depending instead on an as yet unidentified GTP exchange factor that activates Cdc42. The differential use of small Rho family GTPases to activate the cytoskeleton is consistent with the morphological differences observed in T cells that undergo TEM in response to these distinct recruitment signals. PMID:23420881
Validation Data for Mechanical System Algorithms Used in Building Energy Analysis Programs.
1982-02-01
15 Zone Design 15 Built-Up Air Handler 15 Ventilation Requirements 16 The DES 16 Duct Design 17 Air -Delivery System 17 VAV Operation 17 Constant Volume...observed to operate well at reduced air flows, even at low flow in the so- called surge region. Recommendations 1. The HVAC system and component...With Inlet Guide Vanes Operating Within a Built-Up Air Handler 31 Test 2 -- Boiler Operation, Capacity, Efficiency, and Stand-By Losses 32 Test 3
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Woohyun; Katipamula, Srinivas; Lutes, Robert G.
This report describes how the intelligent load control (ILC) algorithm can be implemented to achieve peak demand reduction while minimizing impacts on occupant comfort. The algorithm was designed to minimize the additional sensors and minimum configuration requirements to enable a scalable and cost-effective implementation for both large and small-/medium-sized commercial buildings. The ILC algorithm uses an analytic hierarchy process (AHP) to dynamically prioritize the available curtailable loads based on both quantitative (deviation of zone conditions from set point) and qualitative rules (types of zone). Although the ILC algorithm described in this report was highly tailored to work with rooftop units,more » it can be generalized for application to other building loads such as variable-air-volume (VAV) boxes and lighting systems.« less
Dios-Esponera, Ana; Isern de Val, Soledad; Sevilla-Movilla, Silvia; García-Verdugo, Rosa; García-Bernal, David; Arellano-Sánchez, Nohemí; Cabañas, Carlos; Teixidó, Joaquin
2015-01-01
Stimulation by chemokines of integrin α4β1–dependent T-lymphocyte adhesion is a crucial step for lymphocyte trafficking. The adaptor Vav1 is required for chemokine-activated T-cell adhesion mediated by α4β1. Conceivably, proteins associating with Vav1 could potentially modulate this adhesion. Correlating with activation by the chemokine CXCL12 of T-lymphocyte attachment to α4β1 ligands, a transient stimulation in the association of Vav1 with SLP-76, Pyk2, and ADAP was observed. Using T-cells depleted for SLP-76, ADAP, or Pyk2, or expressing Pyk2 kinase–inactive forms, we show that SLP-76 and ADAP stimulate chemokine-activated, α4β1-mediated adhesion, whereas Pyk2 opposes T-cell attachment. While CXCL12-promoted generation of high-affinity α4β1 is independent of SLP-76, ADAP, and Pyk2, the strength of α4β1-VCAM-1 interaction and cell spreading on VCAM-1 are targets of regulation by these three proteins. GTPase assays, expression of activated or dominant-negative Rac1, or combined ADAP and Pyk2 silencing indicated that Rac1 activation by CXCL12 is a common mediator response in SLP-76–, ADAP-, and Pyk2-regulated cell adhesion involving α4β1. Our data strongly suggest that chemokine-stimulated associations between Vav1, SLP-76, and ADAP facilitate Rac1 activation and α4β1-mediated adhesion, whereas Pyk2 opposes this adhesion by limiting Rac1 activation. PMID:26202465
Avoiding low frequency noise in packaged HVAC equipment
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ebbing, C.E.; Blazier, W.E.Jr.
1993-06-01
The purpose of this article is to help those involved in the design and commissioning of packaged HVAC systems to understand the root causes of low frequency noise problems and how to avoid many of them at the design stage. In the 1980's, two things happened to dramatically change the types of noise problems encountered in typical new construction. The first was the introduction of new energy regulations that favored variable air volume (VAV) distribution systems over constant volume air distribution systems. A by-product of VAV design is that mid- and high frequency sound pressure levels produced by current airmore » terminal devices and diffusers in many applications are significantly lower than in the past. The second factor was a trend away from the use of built-up central station fan equipment in favor of packaged, floor-by-floor air handlers or rooftop units. As a result, today's HVAC system noise problems are not confined to just the roar and hiss of the past, but now include intense low frequency rumble and time modulation. Indeed, most current noise problems in modern buildings occur in the frequency range well below 250 Hz. A large fraction of these are a result of the dominant sound pressure levels in the 12 to 40 Hz region. These factors, combined with a substantial increase in the level of low frequency sound from the rest of the system, can produce a non-neutral, time modulated, rumbly sounding background noise that many people find objectionable.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Khan, Yasin; Mathur, Jyotirmay; Bhandari, Mahabir S
2016-01-01
The paper describes a case study of an information technology office building with a radiant cooling system and a conventional variable air volume (VAV) system installed side by side so that performancecan be compared. First, a 3D model of the building involving architecture, occupancy, and HVAC operation was developed in EnergyPlus, a simulation tool. Second, a different calibration methodology was applied to develop the base case for assessing the energy saving potential. This paper details the calibration of the whole building energy model to the component level, including lighting, equipment, and HVAC components such as chillers, pumps, cooling towers, fans,more » etc. Also a new methodology for the systematic selection of influence parameter has been developed for the calibration of a simulated model which requires large time for the execution. The error at the whole building level [measured in mean bias error (MBE)] is 0.2%, and the coefficient of variation of root mean square error (CvRMSE) is 3.2%. The total errors in HVAC at the hourly are MBE = 8.7% and CvRMSE = 23.9%, which meet the criteria of ASHRAE 14 (2002) for hourly calibration. Different suggestions have been pointed out to generalize the energy saving of radiant cooling system through the existing building system. So a base case model was developed by using the calibrated model for quantifying the energy saving potential of the radiant cooling system. It was found that a base case radiant cooling system integrated with DOAS can save 28% energy compared with the conventional VAV system.« less
Kisiel, John B; Klepp, Pasquale; Allawi, Hatim T; Taylor, William R; Giakoumopoulos, Maria; Sander, Tamara; Yab, Tracy C; Moum, Bjorn A; Lidgard, Graham P; Brackmann, Stephan; Mahoney, Douglas W; Roseth, Arne; Ahlquist, David A
2018-05-15
Patients with inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are at increased risk for colorectal cancer (CRC). Analyses of DNA methylation patterns in stool samples have been reported to detect CRC in patients with IBD. We sought to validate these findings in larger cohorts and assess the accuracy of analysis of DNA methylation patterns in stool for detection of CRC and high-grade dysplasia (HGD) normalized to methylation level at ZDHHC1. We obtained buffered, frozen stool samples from a United States case-control study and from 2 European surveillance cohorts (referral or population based) of patients with chronic UC (n=248), CD (n=82), indeterminate colitis (n=2), or IBD with primary sclerosing cholangitis (n=38). Stool samples were collected before bowel preparation for colonoscopy or at least 1 week after colonoscopy. Among the study samples, stools from individuals with IBD but without neoplasia were used as controls (n=291). DNA was isolated from stool, exposed to bisulfite, and then assayed by multiplex quantitative allele-specific real-time target and signal amplification. We analyzed methylation levels of BMP3, NDRG4, VAV3, and SFMBT2 relative to the methylation level of ZDHHC1, and compared these between patients with CRC or HGD and controls. Levels of methylation at BMP3 and VAV3, relative to ZDHHC1 methylation, identified patients with CRC and HGD with an area under curve value of 0.91 (95% CI, 0.77-1.00). Methylation levels at specific promotor regions of these genes identified 11 of the 12 patients with CRC and HGD, with 92% sensitivity (95% CI, 60%-100%) and 90% specificity (95% CI, 86%-93%). The proportion of false-positive results did not differ significantly among the case-control, referral cohort, and population cohort studies (P=.60) when the 90% specificity cut-off from the whole sample set was applied. In an analysis of stool samples from 3 independent studies, of 332 patients with IBD, we associated levels of methylation at 2 genes (BMP3 and VAV3), relative to level of methylation at ZDHHC1, with detection of CRC and HGD. These methylation patterns identified patients with CRC and HGD with more than 90% specificity, and might be used in CRC surveillance. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Im, Piljae; Munk, Jeffrey D; Gehl, Anthony C
2015-06-01
A research project “Evaluation of Variable Refrigerant Flow (VRF) Systems Performance and the Enhanced Control Algorithm on Oak Ridge National Laboratory’s (ORNL’s) Flexible Research Platform” was performed to (1) install and validate the performance of Samsung VRF systems compared with the baseline rooftop unit (RTU) variable-air-volume (VAV) system and (2) evaluate the enhanced control algorithm for the VRF system on the two-story flexible research platform (FRP) in Oak Ridge, Tennessee. Based on the VRF system designed by Samsung and ORNL, the system was installed from February 18 through April 15, 2014. The final commissioning and system optimization were completed onmore » June 2, 2014, and the initial test for system operation was started the following day, June 3, 2014. In addition, the enhanced control algorithm was implemented and updated on June 18. After a series of additional commissioning actions, the energy performance data from the RTU and the VRF system were monitored from July 7, 2014, through February 28, 2015. Data monitoring and analysis were performed for the cooling season and heating season separately, and the calibrated simulation model was developed and used to estimate the energy performance of the RTU and VRF systems. This final report includes discussion of the design and installation of the VRF system, the data monitoring and analysis plan, the cooling season and heating season data analysis, and the building energy modeling study« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Im, Piljae; Malhotra, Mini; Munk, Jeffrey D.
The performance of two HVAC systems was evaluated using ORNL’s FRP, which is a two-story, 3,200 ft2 (297.3 m2) multi-zone unoccupied building that represents a typical low-rise, small office building common in the US existing building stock. The FRP is equipped with a conventional 12.5 ton (44 kW) RTU-VAV reheat system as the baseline system. For this study, a 12 ton (42 kW) VRF with a dedicated outdoor air system (DOAS) was installed to be compared with the baseline RTU system.
2017-03-01
Systems March 2017 This document has been cleared for public release; Distribution Statement A REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704... FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) 28-02-2017 2. REPORT TYPE Cost and Performance Report 3. DATES COVERED (From - To) September...ABSTRACT c. THIS PAGE 71 19b. TELEPHONE NUMBER (include area code) (515)965-7342 Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Page
Dios-Esponera, Ana; Isern de Val, Soledad; Sevilla-Movilla, Silvia; García-Verdugo, Rosa; García-Bernal, David; Arellano-Sánchez, Nohemí; Cabañas, Carlos; Teixidó, Joaquin
2015-09-15
Stimulation by chemokines of integrin α4β1-dependent T-lymphocyte adhesion is a crucial step for lymphocyte trafficking. The adaptor Vav1 is required for chemokine-activated T-cell adhesion mediated by α4β1. Conceivably, proteins associating with Vav1 could potentially modulate this adhesion. Correlating with activation by the chemokine CXCL12 of T-lymphocyte attachment to α4β1 ligands, a transient stimulation in the association of Vav1 with SLP-76, Pyk2, and ADAP was observed. Using T-cells depleted for SLP-76, ADAP, or Pyk2, or expressing Pyk2 kinase-inactive forms, we show that SLP-76 and ADAP stimulate chemokine-activated, α4β1-mediated adhesion, whereas Pyk2 opposes T-cell attachment. While CXCL12-promoted generation of high-affinity α4β1 is independent of SLP-76, ADAP, and Pyk2, the strength of α4β1-VCAM-1 interaction and cell spreading on VCAM-1 are targets of regulation by these three proteins. GTPase assays, expression of activated or dominant-negative Rac1, or combined ADAP and Pyk2 silencing indicated that Rac1 activation by CXCL12 is a common mediator response in SLP-76-, ADAP-, and Pyk2-regulated cell adhesion involving α4β1. Our data strongly suggest that chemokine-stimulated associations between Vav1, SLP-76, and ADAP facilitate Rac1 activation and α4β1-mediated adhesion, whereas Pyk2 opposes this adhesion by limiting Rac1 activation. © 2015 Dios-Esponera, Isern de Val, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
Dynamic evaluation of airflow rates for a variable air volume system serving an open-plan office.
Mai, Horace K W; Chan, Daniel W T; Burnett, John
2003-09-01
In a typical air-conditioned office, the thermal comfort and indoor air quality are sustained by delivering the amount of supply air with the correct proportion of outdoor air to the breathing zone. However, in a real office, it is not easy to measure these airflow rates supplied to space, especially when the space is served by a variable air volume (VAV) system. The most accurate method depends on what is being measured, the details of the building and types of ventilation system. The constant concentration tracer gas method as a means to determine ventilation system performance, however, this method becomes more complicated when the air, including the tracer gas is allowed to recirculate. An accurate measurement requires significant resource support in terms of instrumentation set up and also professional interpretation. This method deters regular monitoring of the performance of an airside systems by building managers, and hence the indoor environmental quality, in terms of thermal comfort and indoor air quality, may never be satisfactory. This paper proposes a space zone model for the calculation of all the airflow parameters based on tracer gas measurements, including flow rates of outdoor air, VAV supply, return space, return and exfiltration. Sulphur hexafluoride (SF6) and carbon dioxide (CO2) are used as tracer gases. After using both SF6 and CO2, the corresponding results provide a reference to justify the acceptability of using CO2 as the tracer gas. The validity of using CO2 has the significance that metabolic carbon dioxide can be used as a means to evaluate real time airflow rates. This approach provides a practical protocol for building managers to evaluate the performance of airside systems.
Pradip, De; Bouzyk, Mark; Dey, Nandini; Leyland-Jones, Brian
2013-01-01
Amplification of human Her2 and its aberrant signaling in 20-30% of early breast cancer patients is responsible for highly aggressive tumors with poor outcome. Grb7 is reported to be co-amplified with Her2. We report a concurrent high expression of mRNA (from FFPE tumor samples; mRNA correlation, Pearson r(2)= 0.806), and high levels of GRB7 protein (immunoblot) in HER2+ breast cancer cell lines. We demonstrated the signaling mechanism of HER2 and downstream effectors that contributes to proliferation and migration. Using HER2+ and trastuzumab-resistant breast cancer cell lines, we identified the interaction between GRB7 and HER2 in the control of HER2+ cell proliferation. Our co-IP data show that GRB7 recruits SHC into the HER2-GRB7 signaling complex. This complex formation leads to activation of RAS-GTP. We also observed that following integrin engagement, GRB7 is phosphorylated at tyrosine in a p-FAK (Y397) dependent manner. This FAK-GRB7 complex leads to downstream activation of RAC1-GTP (responsible for migration) probably through the recruitment of VAV2. Our CO-IP data demonstrate that GRB7 directly binds with VAV2 following fibronectin engagement in HER2+ cells. To address whether GRB7 could serve as a pathway specific therapeutic target, we used siRNA to suppress GRB7 expression. Knockdown of GRB7 expression in the HER2+ breast cancer cell lines decreases RAS activation, cell proliferation, 2D and 3D colony formation and also blocked integrin-mediated RAC1 activation along with integrin-directed cell migration. These findings dissected the HER2-mediated signaling cascade into (1) HER2+ cell proliferation (HER2-GRB7-SHC-RAS) and (2) HER2+ cell migration (alpha5 beta1/alpha4 beta1-FAK-GRB7-VAV2-RAC1). Our data clearly demonstrate that a coupling of GRB7 with HER2 is required for the proliferative and migratory signals in HER2+ breast tumor cells.
Impact of conditional deletion of the pro-apoptotic BCL-2 family member BIM in mice.
Herold, M J; Stuchbery, R; Mérino, D; Willson, T; Strasser, A; Hildeman, D; Bouillet, P
2014-10-09
The pro-apoptotic BH3-only BCL-2 family member BIM is a critical determinant of hematopoietic cell development and homeostasis. It has been argued that the striking hematopoietic abnormalities of BIM-deficient mice (accumulation of lymphocytes and granulocytes) may be the result of the loss of the protein throughout the whole animal rather than a consequence intrinsic to the loss of BIM in hematopoietic cells. To address this issue and allow the deletion of BIM in specific cell types in future studies, we have developed a mouse strain with a conditional Bim allele as well as a new Cre transgenic strain, Vav-CreER, in which the tamoxifen-inducible CreER recombinase (fusion protein) is predominantly expressed in the hematopoietic system. We show that acute loss of BIM in the adult mouse rapidly results in the hematopoietic phenotypes previously observed in mice lacking BIM in all tissues. This includes changes in thymocyte subpopulations, increased white blood cell counts and resistance of lymphocytes to BIM-dependent apoptotic stimuli, such as cytokine deprivation. We have validated this novel conditional Bim knockout mouse model using established and newly developed CreER strains (Rosa26-CreER and Vav-CreER) and will make these exciting new tools for studies on cell death and cancer available.
NASA Astrophysics Data System (ADS)
Bending, Simon J.; Milošević, Milorad V.; Moshchalkov, Victor V.
Hybrid structures composed of superconducting films that are magnetically coupled to arrays of nanoscale ferromagnetic dots have attracted enormous interest in recent years. Broadly speaking, such systems fall into one of two distinct regimes. Ferromagnetic dots with weak moments pin free vortices, leading to enhanced superconducting critical currents, particularly when the conditions for commensurability are satisfied. Dots with strong moments spontaneously generate one or more vortex-antivortex (V-AV) pairs which lead to a rich variety of pinning, anti-pinning and annihilation phenomena. We describe high resolution Hall probe microscopy of flux structures in various hybrid samples composed of superconducting Pb films deposited on arrays of ferromagnetic Co or Co/Pt dots with both weak and strong moments. We show directly that dots with very weak perpendicular magnetic moments do not induce vortex-antivortex pairs, but still act as strong polarity-dependent vortex pinning centres for free vortices. In contrast, we have directly observed spontaneous V-AV pairs induced by large moment dots with both in-plane and perpendicular magnetic anisotropy, and studied the rich physical phenomena that arise when they interact with added "free" (anti)fluxons in an applied magnetic field. The interpretation of our imaging results is supported by bulk magnetometry measurements and state-of-the-art Ginzburg-Landau and London theory calculations.
Perez-Cunningham, Jessica; Boyer, Scott W; Landon, Mark; Forsberg, E Camilla
2016-08-01
Selective labeling of specific cell types by expression of green fluorescent protein (GFP) within the hematopoietic system would have great utility in identifying, localizing, and tracking different cell populations in flow cytometry, microscopy, lineage tracing, and transplantation assays. In this report, we describe the generation and characterization of a new transgenic mouse line with specific GFP labeling of all nucleated hematopoietic cells and platelets. This new "Vav-GFP" mouse line labels the vast majority of hematopoietic cells with GFP during both embryonic development and adulthood, with particularly high expression in hematopoietic stem and progenitor cells (HSPCs). With the exception of transient labeling of fetal endothelial cells, GFP expression is highly selective for hematopoietic cells and persists in donor-derived progeny after transplantation of HSPCs. Finally, we also demonstrate that the loxP-flanked reporter allows for specific GFP labeling of different hematopoietic cell subsets when crossed to various Cre reporter lines. By crossing Vav-GFP mice to Flk2-Cre mice, we obtained robust and highly selective GFP expression in hematopoietic stem cells (HSCs). These data describe a new mouse model capable of directing GFP labeling exclusively of hematopoietic cells or exclusively of HSCs. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chihara, Kazuyasu; Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193; Kimura, Yukihiro
Adaptor protein c-Abl SH3 domain-binding protein-2 (3BP2) is known to play regulatory roles in immunoreceptor-mediated signal transduction. We have previously demonstrated that Tyr{sup 174}, Tyr{sup 183} and Tyr{sup 446} in mouse 3BP2 are predominantly phosphorylated by Syk, and the phosphorylation of Tyr{sup 183} and the Src homology 2 (SH2) domain of mouse 3BP2 are critical for B cell receptor (BCR)-induced activation of nuclear factor of activated T cells (NFAT) in human B cells. In this report, we have shown that Syk, but not Abl family protein-tyrosine kinases, is critical for BCR-mediated tyrosine phosphorylation of 3BP2 in chicken DT40 cells. Mutationalmore » analysis showed that Tyr{sup 174}, Tyr{sup 183} and Tyr{sup 426} of chicken 3BP2 are the major phosphorylation sites by Syk and the SH2 domain of 3BP2 is critical for tyrosine phosphorylation. In addition, phosphorylation of Tyr{sup 426} is required for the inducible interaction with the SH2 domain of Vav3. Moreover, the expression of the mutant form of 3BP2 in which Tyr{sup 426} was substituted to Phe resulted in the reduction in BCR-mediated Rac1 activation, when compared with the case of wild-type. Altogether, these data suggest that 3BP2 is involved in the activation of Rac1 through the regulation of Vav3 by Syk-dependent phosphorylation of Tyr{sup 426} following BCR stimulation. - Highlights: • 3BP2 is phosphorylated by Syk, but not Abl family kinases in BCR signaling. • Tyr183 and Tyr426 in chicken 3BP2 are the major phosphorylation sites by Syk. • The SH2 domain of 3BP2 is critical for tyrosine phosphorylation of 3BP2. • Phosphorylation of Tyr426 in 3BP2 is required for the inducible binding with Vav3. • 3BP2 is involved in the regulation of BCR-mediated Rac1 activation.« less
Yong, Carmen S.M.; John, Liza B.; Devaud, Christel; Prince, Miles H.; Johnstone, Ricky W.; Trapani, Joseph A.
2016-01-01
While adoptive immunotherapy using chimeric antigen receptor (CAR)-modified T cells can induce remission of some tumors, the role of other CAR-modified leukocytes is not well characterized. In this study, we characterize the function of leukocytes including natural killer (NK) cells, macrophages and CAR T cells from transgenic mice expressing a CAR under the control of the pan-hematopoietic promoter, vav, and determine the ability of these mice to respond to ERB expressing tumors. We demonstrate the anti-tumor functions of leukocytes, including antigen specific cytotoxicity and cytokine secretion. The adoptive transfer of CAR T cells provided a greater survival advantage in the E0771ERB tumor model than their wildtype (WT) counterparts. In addition, CAR NK cells and CAR T cells also mediated increased survival in the RMAERB tumor model. When challenged with Her2 expressing tumors, F38 mice were shown to mount an effective immune response, resulting in tumor rejection and long-term survival. This was shown to be predominantly dependent on both CD8+ T cells and NK cells. However, macrophages and CD4+ T cells were also shown to contribute to this response. Overall, this study highlights the use of the vav-CAR mouse model as a unique tool to determine the anti-tumor function of various immune subsets, either alone or when acting alongside CAR T cells in adoptive immunotherapy. PMID:27153556
Detection of protein-protein interactions by ribosome display and protein in situ immobilisation.
He, Mingyue; Liu, Hong; Turner, Martin; Taussig, Michael J
2009-12-31
We describe a method for identification of protein-protein interactions by combining two cell-free protein technologies, namely ribosome display and protein in situ immobilisation. The method requires only PCR fragments as the starting material, the target proteins being made through cell-free protein synthesis, either associated with their encoding mRNA as ribosome complexes or immobilised on a solid surface. The use of ribosome complexes allows identification of interacting protein partners from their attached coding mRNA. To demonstrate the procedures, we have employed the lymphocyte signalling proteins Vav1 and Grb2 and confirmed the interaction between Grb2 and the N-terminal SH3 domain of Vav1. The method has promise for library screening of pairwise protein interactions, down to the analytical level of individual domain or motif mapping.
Ofloxacin induces apoptosis via β1 integrin-EGFR-Rac1-Nox2 pathway in microencapsulated chondrocytes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sheng, Zhi-Guo; Huang, Wei; Liu, Yu-Xiang
2013-02-15
Quinolones (QNs)-induced arthropathy is an important toxic side-effect in immature animals leading to the restriction of their therapeutic use in pediatrics. Ofloxacin, a typical QN, was found to induce the chondrocytes apoptosis in the early phase (12–48 h) of arthropathy in our previous study. However, the exact mechanism(s) is unclear. Microencapsulated juvenile rabbit joint chondrocytes, a three-dimensional culture system, is utilized to perform the present study. Ofloxacin, at a therapeutically relevant concentration (10 μg/ml), disturbs the interaction between β1 integrin and activated intracellular signaling proteins at 12 h, which is inhibited when supplementing Mg{sup 2+}. Intracellular reactive oxygen species (ROS)more » significantly increases in a time-dependent manner after exposure to ofloxacin for 12–48 h. Furthermore, ofloxacin markedly enhances the level of activated Rac1 and epidermal growth factor receptor (EGFR) phosphorylation, and its inhibition in turn reduces the ROS production, apoptosis and Rac1 activation. Silencing Nox2, Rac1 or supplementing Mg{sup 2+} inhibits ROS accumulation, apoptosis occurrence and EGFR phosphorylation induced by ofloxacin. However, depletion of Nox2, Rac1 and inhibition of EGFR do not affect ofloxacin-mediated loss of interaction between β1 integrin and activated intracellular signaling proteins. In addition, ofloxacin also induces Vav2 phosphorylation, which is markedly suppressed after inactivating EGFR or supplementing Mg{sup 2+}. These results suggest that ofloxacin causes Nox2-mediated intracellular ROS production by disrupting the β1 integrin function and then activating the EGFR-Vav2-Rac1 pathway, finally resulting in apoptosis within 12–48 h exposure. The present study provides a novel insight regarding the potential role of Nox-driven ROS in QNs-induced arthropathy. - Highlights: ► Ofloxacin induces Nox2-driven ROS in encapsulated chondrocyte at 12–48 h. ► Ofloxacin stimulates ROS production via the β1 integrin-EGFR-Vav2-Rac1 pathway. ► Ofloxacin induces ROS-dependent apoptosis in encapsulated chondrocyte at 12–48 h.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Im, Piljae; Malhotra, Mini; Munk, Jeffrey D.
This report provides second-year cooling season test results for the multi-year project titled “Evaluation of Variable Refrigeration Flow (VRF) System on Oak Ridge National Laboratory (ORNL)’s Flexible Research Platform (FRP).” The purpose of the second-year project was to (1) evaluate the full- and partload performance of VRF systems compared with an existing baseline heating, ventilation, and airconditioning (HVAC) system, which is a conventional rooftop unit (RTU) variable-air-volume (VAV) system with electric resistance heating and (2) use hourly building energy simulation to evaluate the energy savings potential of using VRF systems in major US cities. The second-year project performance period wasmore » from July 2015 through June 2016.« less
The AhR agonist VAF347 augments retinoic acid-induced differentiation in leukemia cells
Ibabao, Christopher N.; Bunaciu, Rodica P.; Schaefer, Deanna M.W.; Yen, Andrew
2015-01-01
In binary cell-fate decisions, driving one lineage and suppressing the other are conjoined. We have previously reported that aryl hydrocarbon receptor (AhR) promotes retinoic acid (RA)-induced granulocytic differentiation of lineage bipotent HL-60 myeloblastic leukemia cells. VAF347, an AhR agonist, impairs the development of CD14+CD11b+ monocytes from granulo-monocytic (GM) stage precursors. We thus hypothesized that VAF347 propels RA-induced granulocytic differentiation and impairs D3-induced monocytic differentiation of HL-60 cells. Our results show that VAF347 enhanced RA-induced cell cycle arrest, CD11b integrin expression and neutrophil respiratory burst. Granulocytic differentiation is known to be driven by MAPK signaling events regulated by Fgr and Lyn Src-family kinases, the CD38 cell membrane receptor, the Vav1 GEF, the c-Cbl adaptor, as well as AhR, all of which are embodied in a putative signalsome. We found that the VAF347 AhR ligand regulates the signalsome. VAF347 augments RA-induced expression of AhR, Lyn, Vav1, and c-Cbl as well as p47phox. Several interactions of partners in the signalsome appear to be enhanced: Fgr interaction with c-Cbl, CD38, and with pS259c-Raf and AhR interaction with c-Cbl and Lyn. Thus, we report that, while VAF347 impedes monocytic differentiation induced by 1,25-dihydroxyvitamin D3, VAF347 promotes RA-induced differentiation. This effect seems to involve but not to be limited to Lyn, Vav1, c-Cbl, AhR, and Fgr. PMID:25941627
Chihara, Kazuyasu; Kimura, Yukihiro; Honjoh, Chisato; Yamauchi, Shota; Takeuchi, Kenji; Sada, Kiyonao
2014-03-10
Adaptor protein c-Abl SH3 domain-binding protein-2 (3BP2) is known to play regulatory roles in immunoreceptor-mediated signal transduction. We have previously demonstrated that Tyr(174), Tyr(183) and Tyr(446) in mouse 3BP2 are predominantly phosphorylated by Syk, and the phosphorylation of Tyr(183) and the Src homology 2 (SH2) domain of mouse 3BP2 are critical for B cell receptor (BCR)-induced activation of nuclear factor of activated T cells (NFAT) in human B cells. In this report, we have shown that Syk, but not Abl family protein-tyrosine kinases, is critical for BCR-mediated tyrosine phosphorylation of 3BP2 in chicken DT40 cells. Mutational analysis showed that Tyr(174), Tyr(183) and Tyr(426) of chicken 3BP2 are the major phosphorylation sites by Syk and the SH2 domain of 3BP2 is critical for tyrosine phosphorylation. In addition, phosphorylation of Tyr(426) is required for the inducible interaction with the SH2 domain of Vav3. Moreover, the expression of the mutant form of 3BP2 in which Tyr(426) was substituted to Phe resulted in the reduction in BCR-mediated Rac1 activation, when compared with the case of wild-type. Altogether, these data suggest that 3BP2 is involved in the activation of Rac1 through the regulation of Vav3 by Syk-dependent phosphorylation of Tyr(426) following BCR stimulation. Copyright © 2014 Elsevier Inc. All rights reserved.
The AhR agonist VAF347 augments retinoic acid-induced differentiation in leukemia cells.
Ibabao, Christopher N; Bunaciu, Rodica P; Schaefer, Deanna M W; Yen, Andrew
2015-01-01
In binary cell-fate decisions, driving one lineage and suppressing the other are conjoined. We have previously reported that aryl hydrocarbon receptor (AhR) promotes retinoic acid (RA)-induced granulocytic differentiation of lineage bipotent HL-60 myeloblastic leukemia cells. VAF347, an AhR agonist, impairs the development of CD14(+)CD11b(+) monocytes from granulo-monocytic (GM) stage precursors. We thus hypothesized that VAF347 propels RA-induced granulocytic differentiation and impairs D3-induced monocytic differentiation of HL-60 cells. Our results show that VAF347 enhanced RA-induced cell cycle arrest, CD11b integrin expression and neutrophil respiratory burst. Granulocytic differentiation is known to be driven by MAPK signaling events regulated by Fgr and Lyn Src-family kinases, the CD38 cell membrane receptor, the Vav1 GEF, the c-Cbl adaptor, as well as AhR, all of which are embodied in a putative signalsome. We found that the VAF347 AhR ligand regulates the signalsome. VAF347 augments RA-induced expression of AhR, Lyn, Vav1, and c-Cbl as well as p47(phox). Several interactions of partners in the signalsome appear to be enhanced: Fgr interaction with c-Cbl, CD38, and with pS259c-Raf and AhR interaction with c-Cbl and Lyn. Thus, we report that, while VAF347 impedes monocytic differentiation induced by 1,25-dihydroxyvitamin D3, VAF347 promotes RA-induced differentiation. This effect seems to involve but not to be limited to Lyn, Vav1, c-Cbl, AhR, and Fgr.
Using coordinate-based meta-analyses to explore structural imaging genetics.
Janouschek, Hildegard; Eickhoff, Claudia R; Mühleisen, Thomas W; Eickhoff, Simon B; Nickl-Jockschat, Thomas
2018-05-05
Imaging genetics has become a highly popular approach in the field of schizophrenia research. A frequently reported finding is that effects from common genetic variation are associated with a schizophrenia-related structural endophenotype. Genetic contributions to a structural endophenotype may be easier to delineate, when referring to biological rather than diagnostic criteria. We used coordinate-based meta-analyses, namely the anatomical likelihood estimation (ALE) algorithm on 30 schizophrenia-related imaging genetics studies, representing 44 single-nucleotide polymorphisms at 26 gene loci investigated in 4682 subjects. To test whether analyses based on biological information would improve the convergence of results, gene ontology (GO) terms were used to group the findings from the published studies. We did not find any significant results for the main contrast. However, our analysis enrolling studies on genotype × diagnosis interaction yielded two clusters in the left temporal lobe and the medial orbitofrontal cortex. All other subanalyses did not yield any significant results. To gain insight into possible biological relationships between the genes implicated by these clusters, we mapped five of them to GO terms of the category "biological process" (AKT1, CNNM2, DISC1, DTNBP1, VAV3), then five to "cellular component" terms (AKT1, CNNM2, DISC1, DTNBP1, VAV3), and three to "molecular function" terms (AKT1, VAV3, ZNF804A). A subsequent cluster analysis identified representative, non-redundant subsets of semantically similar terms that aided a further interpretation. We regard this approach as a new option to systematically explore the richness of the literature in imaging genetics.
75 FR 54446 - Voluntary Service National Advisory Committee; Notice of Meeting
Federal Register 2010, 2011, 2012, 2013, 2014
2010-09-07
...-four national voluntary organizations, advises the Secretary, through the Under Secretary for Health... DEPARTMENT OF VETERANS AFFAIRS Voluntary Service National Advisory Committee; Notice of Meeting... Committee Act) that the Executive Committee of the Department of Veterans Affairs Voluntary Service (VAVS...
Dual role of SLP-76 in mediating T cell receptor-induced activation of phospholipase C-gamma1.
Beach, Dvora; Gonen, Ronnie; Bogin, Yaron; Reischl, Ilona G; Yablonski, Deborah
2007-02-02
Phospholipase C-gamma1 (PLC-gamma1) activation depends on a heterotrimeric complex of adaptor proteins composed of LAT, Gads, and SLP-76. Upon T cell receptor stimulation, a portion of PLC-gamma1 is recruited to a detergent-resistant membrane fraction known as the glycosphingolipid-enriched membrane microdomains (GEMs), or lipid rafts, to which LAT is constitutively localized. In addition to LAT, PLC-gamma1 GEM recruitment depended on SLP-76, and, in particular, required the Gads-binding domain of SLP-76. The N-terminal tyrosine phosphorylation sites and P-I region of SLP-76 were not required for PLC-gamma1 GEM recruitment, but were required for PLC-gamma1 phosphorylation at Tyr(783). Thus, GEM recruitment can be insufficient for full activation of PLC-gamma1 in the absence of a second SLP-76-mediated event. Indeed, a GEM-targeted derivative of PLC-gamma1 depended on SLP-76 for T cell receptor-induced phosphorylation at Tyr783 and subsequent NFAT activation. On a biochemical level, SLP-76 inducibly associated with both Vav and catalytically active ITK, which efficiently phosphorylated a PLC-gamma1 fragment at Tyr783 in vitro. Both associations were disrupted upon mutation of the N-terminal tyrosine phosphorylation sites of SLP-76. The P-I region deletion disrupted Vav association and reduced SLP-76-associated kinase activity. A smaller deletion within the P-I region, which does not impair PLC-gamma1 activation, did not impair the association with Vav, but reduced SLP-76-associated kinase activity. These results provide new insight into the multiple roles of SLP-76 and the functional importance of its interactions with other signaling proteins.
An, Wei; Mohapatra, Bhopal C.; Zutshi, Neha; Bielecki, Timothy A.; Goez, Benjamin T.; Luan, Haitao; Iseka, Fany; Mushtaq, Insha; Storck, Matthew D.; Band, Vimla; Band, Hamid
2016-01-01
CBL and CBL-B ubiquitin ligases play key roles in hematopoietic stem cell homeostasis and their aberrations are linked to leukemogenesis. Mutations of CBL, often genetically-inherited, are particularly common in Juvenile Myelomonocytic Leukemia (JMML), a disease that manifests early in children. JMML is fatal unless corrected by bone marrow transplant, which is effective in only half of the recipients, stressing the need for animal models that recapitulate the key clinical features of this disease. However, mouse models established so far only develop hematological malignancy in adult animals. Here, using VAV1-Cre-induced conditional CBL/CBL-B double knockout (DKO) in mice, we established an animal model that exhibits a neonatal myeloproliferative disease (MPD). VAV1-Cre induced DKO mice developed a strong hematological phenotype at postnatal day 10, including severe leukocytosis and hepatomegaly, bone marrow cell hypersensitivity to cytokines including GM-CSF, and rapidly-progressive disease and invariable lethality. Interestingly, leukemic stem cells were most highly enriched in neonatal liver rather than bone marrow, which, along with the spleen and thymus, were hypo-cellular. Nonetheless, transplantation assays showed that both DKO bone marrow and liver cells can initiate leukemic disease in the recipient mice with seeding of both spleen and bone marrow. Together, our results support the usefulness of the new hematopoietic-specific CBL/CBL-B double KO animal model to study JMML-related pathogenesis and to further understand the function of CBL family proteins in regulating fetal and neonatal hematopoiesis. To our knowledge, this is the first mouse model that exhibits neonatal MPD in infancy, by day 10 of postnatal life. PMID:27449297
Performance evaluation of radiant cooling system application on a university building in Indonesia
NASA Astrophysics Data System (ADS)
Satrio, Pujo; Sholahudin, S.; Nasruddin
2017-03-01
The paper describes a study developed to estimate the energy savings potential of a radiant cooling system installed in an institutional building in Indonesia. The simulations were carried out using IESVE to evaluate thermal performance and energy consumption The building model was calibrated using the measured data for the installed radiant system. Then this calibrated model was used to simulate the energy consumption and temperature distribution to determine the proportional energy savings and occupant comfort under different systems. The result was radiant cooling which integrated with a Dedicated Outside Air System (DOAS) could make 41,84% energy savings compared to the installed cooling system. The Computational Fluid Dynamics (CFD) simulation showed that a radiant system integrated with DOAS provides superior human comfort than a radiant system integrated with Variable Air Volume (VAV). Percentage People Dissatisfied was kept below 10% using the proposed system.
77 FR 60507 - Voluntary Service National Advisory Committee; Notice of Meeting
Federal Register 2010, 2011, 2012, 2013, 2014
2012-10-03
... meeting is open to the public. The Committee, comprised of 57 national voluntary organizations, advises... DEPARTMENT OF VETERANS AFFAIRS Voluntary Service National Advisory Committee; Notice of Meeting... Committee Act) that the Executive Committee of the Department of Veterans Affairs Voluntary Service (VAVS...
Peralta-Arrieta, Irlanda; Hernández-Sotelo, Daniel; Castro-Coronel, Yaneth; Leyva-Vázquez, Marco Antonio; Illades-Aguiar, Berenice
2017-01-01
Altered promoter DNA methylation is one of the most important epigenetic abnormalities in human cancer. DNMT3B, de novo methyltransferase, is clearly related to abnormal methylation of tumour suppressor genes, DNA repair genes and its overexpression contributes to oncogenic processes and tumorigenesis in vivo. The purpose of this study was to assess the effect of the overexpression of DNMT3B in HaCaT cells on global gene expression and on the methylation of selected genes to the identification of genes that can be target of DNMT3B. We found that the overexpression of DNMT3B in HaCaT cells, modulate the expression of genes related to cancer, downregulated the expression of 151 genes with CpG islands and downregulated the expression of the VAV3 gene via methylation of its promoter. These results highlight the importance of DNMT3B in gene expression and human cancer. PMID:28123849
Peralta-Arrieta, Irlanda; Hernández-Sotelo, Daniel; Castro-Coronel, Yaneth; Leyva-Vázquez, Marco Antonio; Illades-Aguiar, Berenice
2017-01-01
Altered promoter DNA methylation is one of the most important epigenetic abnormalities in human cancer. DNMT3B, de novo methyltransferase, is clearly related to abnormal methylation of tumour suppressor genes, DNA repair genes and its overexpression contributes to oncogenic processes and tumorigenesis in vivo . The purpose of this study was to assess the effect of the overexpression of DNMT3B in HaCaT cells on global gene expression and on the methylation of selected genes to the identification of genes that can be target of DNMT3B. We found that the overexpression of DNMT3B in HaCaT cells, modulate the expression of genes related to cancer, downregulated the expression of 151 genes with CpG islands and downregulated the expression of the VAV3 gene via methylation of its promoter. These results highlight the importance of DNMT3B in gene expression and human cancer.
A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress.
Kant, Shashi; Standen, Claire L; Morel, Caroline; Jung, Dae Young; Kim, Jason K; Swat, Wojciech; Flavell, Richard A; Davis, Roger J
2017-09-19
Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA) activation of a non-receptor tyrosine kinase (SRC)-dependent cJun NH 2 -terminal kinase (JNK) signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV. These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module. The JIP1 scaffold protein, therefore, plays a dual role in FFA signaling by coordinating upstream SRC functions together with downstream effector signaling by the JNK pathway. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
Prioritising and planning of urban stormwater treatment in the Alna watercourse in Oslo.
Nordeidet, B; Nordeide, T; Astebøl, S O; Hvitved-Jacobsen, T
2004-12-01
The Oslo municipal Water and Sewage Works (VAV) intends to improve the water quality in the Alna watercourse, in particular, with regards to the biological diversity. In order to reduce existing discharges of polluted urban stormwater, a study has been carried out to rank subcatchment areas in descending order of magnitude and to assess possible measures. An overall ranking methodology was developed in order to identify and select the most suitable subcatchment areas for further assessment studies (74 subcatchment/drainage areas). The municipality's comprehensive geographical information system (GIS) was applied as a base for the ranking. A weighted ranking based on three selected parameters was chosen from several major influencing factors, namely total yearly discharge (kg pollution/year), specific pollution discharge (kg/area/year) and existing stormwater system (pipe lengths/area). Results show that the highest 15 ranked catchment areas accounted for 70% of the total calculated pollution load of heavy metals. The highest ranked areas are strongly influenced by three major highways. Based on the results from similar field studies, it would be possible to remove 75-85% of total solids and about 50-80% of heavy metals using wet detention ponds as Best Available Technology (BAT). Based on the final ranking, two subcatchment areas were selected for further practical assessment of possible measures. VAV plans to use wet detention ponds, in combination with other measures when relevant, to treat the urban runoff. Using calculated loading and aerial photographs (all done in the same GIS environment), a preliminary sketch design and location of ponds were performed. The resulting GIS methodology for urban stormwater management will be used as input to a holistic and long-term planning process for the management of the watercourse, taking into account future urban development and other pollution sources.
Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans
Daghighi, Mojtaba; Özcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M.; Mahmoudi, Morteza; De Rooij, Felix W. M.; Sijbrands, Eric; Peppelenbosch, Maikel P.; Rezaee, Farhad
2015-01-01
Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy. AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling). Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs. PMID:26337083
75 FR 4632 - Voluntary Service National Advisory Committee; Notice of Meeting
Federal Register 2010, 2011, 2012, 2013, 2014
2010-01-28
... Awards, VAVS Award for Excellence, and the NAC Volunteer of the Year Awards. The April 8 business session... volunteers, cultural transformation, and assisting homeless veterans. On April 9, the educational workshops will be repeated in the morning and the business session will be held in the afternoon and will include...
Syk Mediates BCR- and CD40-Signaling Intergration during B Cell Activation
Ying, Haiyan; Li, Zhenping; Yang, Lifen; Zhang, Jian
2010-01-01
CD40 is essential for optimal B cell activation. It has been shown that CD40 stimulation can augment BCR-induced B cell responses, but the molecular mechanism(s) by which CD40 regulates BCR signaling is poorly understood. In this report, we attempted to characterize the signaling synergy between BCR- and CD40-mediated pathways during B cell activation. We found that spleen tyrosine kinase (Syk) is involved in CD40 signaling, and is synergistically activated in B cells in response to BCR/CD40 costimulation. CD40 stimulation alone also activates B cell linker (BLNK), Bruton tyrosine kinase (Btk), and Vav-2 downstream of Syk, and significantly enhances BCR-induced formation of complex consisting of, Vav-2, Btk, BLNK, and phospholipase C-gamma2 (PLC-γ2) leading to activation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase, Akt, and NF-κB required for optimal B cell activation. Therefore, our data suggest that CD40 can strengthen BCR-signaling pathway and quantitatively modify BCR signaling during B cell activation. PMID:21074890
Reliability Estimating Procedures for Electric and Thermochemical Propulsion Systems. Volume 1
1977-02-01
Laboratories, The Marquardt Company, NASA Goddard Space Flight Center, RCA Astro Elec- tronics, Rockwell International, Applied Physics Laboratory...E fX ) 2.3 Failure Rate Means and Bounds 5% Lower Bound Median Mean 95% Upper Bound A.05 X.05 . AIA. 9 5 0.00025 0.0024 0.06 0.022 x10- 6 per cycle, 1...Iq IIt. Xg4 4l Wl ~ 4 L Q ൘ I1-269 I- I J N1- 74-i Liu I- (~J~~~jto 1-27 r4J > U 0 1-271 T 27 fX ~ 0L 1-273 -- va VAv( 13 1-272 %J% ~ii 000 41
Bypass Mechanisms of the Androgen Receptor Pathway in Therapy-Resistant Prostate Cancer Cell Models
Marques, Rute B.; Dits, Natasja F.; Erkens-Schulze, Sigrun; van Weerden, Wytske M.; Jenster, Guido
2010-01-01
Background Prostate cancer is initially dependent on androgens for survival and growth, making hormonal therapy the cornerstone treatment for late-stage tumors. However, despite initial remission, the cancer will inevitably recur. The present study was designed to investigate how androgen-dependent prostate cancer cells eventually survive and resume growth under androgen-deprived and antiandrogen supplemented conditions. As model system, we used the androgen-responsive PC346C cell line and its therapy-resistant sublines: PC346DCC, PC346Flu1 and PC346Flu2. Methodology/Principal Findings Microarray technology was used to analyze differences in gene expression between the androgen-responsive and therapy-resistant PC346 cell lines. Microarray analysis revealed 487 transcripts differentially-expressed between the androgen-responsive and the therapy-resistant cell lines. Most of these genes were common to all three therapy-resistant sublines and only a minority (∼5%) was androgen-regulated. Pathway analysis revealed enrichment in functions involving cellular movement, cell growth and cell death, as well as association with cancer and reproductive system disease. PC346DCC expressed residual levels of androgen receptor (AR) and showed significant down-regulation of androgen-regulated genes (p-value = 10−7). Up-regulation of VAV3 and TWIST1 oncogenes and repression of the DKK3 tumor-suppressor was observed in PC346DCC, suggesting a potential AR bypass mechanism. Subsequent validation of these three genes in patient samples confirmed that expression was deregulated during prostate cancer progression. Conclusions/Significance Therapy-resistant growth may result from adaptations in the AR pathway, but androgen-independence may also be achieved by alternative survival mechanisms. Here we identified TWIST1, VAV3 and DKK3 as potential players in the bypassing of the AR pathway, making them good candidates as biomarkers and novel therapeutical targets. PMID:20976069
Liquid transmission characteristics of padding bandages under pressure.
Kumar, Bipin; Das, Apurba; Pan, Ning; Alagirusamy, R; Gupta, Rupali; Singh, Jitender
2015-11-01
Padding is an essential component in a multilayer compression bandaging system, used inside the compression bandage through which substantial amount of pressure is exerted on the limb of patient for treatment of venous leg ulcers. As a result, the liquid transmission behavior of padding is also critical in managing body fluids or sweat exuded from the affected limb, reducing the excessive moisture build-up around the wound and thereby ensuring comfort to and hence a better compliance from the patients. This study investigates the in-plane fluid transport characteristics of needle-punched nonwoven padding bandages. It first reviewed the existing studies related to the problems, and discussed their limits and possible improvements in dealing with complex fluid transport issues in textile porous media. The measurement of fluid transport under different pressure levels was then done using a newly designed apparatus capable of simultaneously tracing the liquid in-plane spreading along different directions, and obtaining several transport characteristics of a testing sample, e.g. the liquid flow anisotropy, the rate of movement, the area of wet surface with time, etc. Also the effects of several important factors, such as the levels of pressure applied, the specimen bulk density, and needling density of the padding products, have been experimentally investigated. In addition, based on an extended Lucas-Washburn theory, we calculated the liquid flow distance, both instantaneous speed and a more useful time-averaged speed v(av) at any given direction, and also defined a flow anisotropy index I(A) as a convenient parameter to represent the material flow anisotropy. The applications of v(av) and I(A) to actual samples have demonstrated the usefulness of these parameters in characterizing the flow nature and behavior of the materials. © The Author(s) 2015.
Neural network based optimal control of HVAC&R systems
NASA Astrophysics Data System (ADS)
Ning, Min
Heating, Ventilation, Air-Conditioning and Refrigeration (HVAC&R) systems have wide applications in providing a desired indoor environment for different types of buildings. It is well acknowledged that 30%-40% of the total energy generated is consumed by buildings and HVAC&R systems alone account for more than 50% of the building energy consumption. Low operational efficiency especially under partial load conditions and poor control are part of reasons for such high energy consumption. To improve energy efficiency, HVAC&R systems should be properly operated to maintain a comfortable and healthy indoor environment under dynamic ambient and indoor conditions with the least energy consumption. This research focuses on the optimal operation of HVAC&R systems. The optimization problem is formulated and solved to find the optimal set points for the chilled water supply temperature, discharge air temperature and AHU (air handling unit) fan static pressure such that the indoor environment is maintained with the least chiller and fan energy consumption. To achieve this objective, a dynamic system model is developed first to simulate the system behavior under different control schemes and operating conditions. The system model is modular in structure, which includes a water-cooled vapor compression chiller model and a two-zone VAV system model. A fuzzy-set based extended transformation approach is then applied to investigate the uncertainties of this model caused by uncertain parameters and the sensitivities of the control inputs with respect to the interested model outputs. A multi-layer feed forward neural network is constructed and trained in unsupervised mode to minimize the cost function which is comprised of overall energy cost and penalty cost when one or more constraints are violated. After training, the network is implemented as a supervisory controller to compute the optimal settings for the system. In order to implement the optimal set points predicted by the supervisory controller, a set of five adaptive PI (proportional-integral) controllers are designed for each of the five local control loops of the HVAC&R system. The five controllers are used to track optimal set points and zone air temperature set points. Parameters of these PI controllers are tuned online to reduce tracking errors. The updating rules are derived from Lyapunov stability analysis. Simulation results show that compared to the conventional night reset operation scheme, the optimal operation scheme saves around 10% energy under full load condition and 19% energy under partial load conditions.
2004-08-01
AF038388 Vav3 GEF for Rho and Rac Proto-oncogene product NM020505 hPEM -2 GEF for Cdc42 Predominantly expressed in brain AB007884 GEF-H1 GEF for Rac and Rho...fence tions, and desmosomes play a fundamental role in maintain- function). A functional tight junction is crucial to maintain ing the polarized phenotype
Buvall, Lisa; Wallentin, Hanna; Sieber, Jonas; Andreeva, Svetlana; Choi, Hoon Young; Mundel, Peter
2017-01-01
Tyrosine and serine/threonine signal-transduction pathways influence many aspects of cell behavior, including the spatial and temporal regulation of the actin cytoskeleton. However, little is known about how input from diverse tyrosine and serine/threonine kinases is integrated to control Rho protein crosstalk and actin remodeling, which are critically important in podocyte health and disease. Here we unveil the proteolytically-regulated, actin organizing protein synaptopodin as a coincidence detector of tyrosine versus serine/threonine phosphorylation. We show that serine/threonine and tyrosine kinases duel for synaptopodin stability versus degradation. EGFR/Src-mediated tyrosine phosphorylation of synaptopodin in podocytes promotes binding to the serine/threonine phosphatase calcineurin. This leads to the loss of 14–3-3 binding, resulting in synaptopodin degradation, Vav2 activation, enhanced Rac1 signaling, and ultimate loss of stress fibers. Our studies reveal how synaptopodin, a single proteolytically-controlled protein, integrates antagonistic tyrosine versus serine/threonine phosphorylation events for the dynamic control of the actin cytoskeleton in podocytes. PMID:27628902
Buvall, Lisa; Wallentin, Hanna; Sieber, Jonas; Andreeva, Svetlana; Choi, Hoon Young; Mundel, Peter; Greka, Anna
2017-03-01
Tyrosine and serine/threonine signal-transduction pathways influence many aspects of cell behavior, including the spatial and temporal regulation of the actin cytoskeleton. However, little is known about how input from diverse tyrosine and serine/threonine kinases is integrated to control Rho protein crosstalk and actin remodeling, which are critically important in podocyte health and disease. Here we unveil the proteolytically-regulated, actin organizing protein synaptopodin as a coincidence detector of tyrosine versus serine/threonine phosphorylation. We show that serine/threonine and tyrosine kinases duel for synaptopodin stability versus degradation. EGFR/Src-mediated tyrosine phosphorylation of synaptopodin in podocytes promotes binding to the serine/threonine phosphatase calcineurin. This leads to the loss of 14-3-3 binding, resulting in synaptopodin degradation, Vav2 activation, enhanced Rac1 signaling, and ultimate loss of stress fibers. Our studies reveal how synaptopodin, a single proteolytically-controlled protein, integrates antagonistic tyrosine versus serine/threonine phosphorylation events for the dynamic control of the actin cytoskeleton in podocytes. Copyright © 2017 by the American Society of Nephrology.
Role of IKK-alpha in the EGFR Signaling Regulation
2014-09-01
Rho family GTPase (VAV2), and Phospholipase C (PLC) (4). These signaling activities regulate cell proliferation, mobility , and differentiation in...correlation coefficient r=0.63, pɘ.05) was found, suggesting that high IKK promotes EGFR phosphorylation in breast cancer cells (Fig. 3G ...phosphorylation (Figure 2E). Since protein phosphorylation sometimes results in a mobility shift in SDS-PAGE, we used a phospho-tag to capture phospho
Field test and simulation evaluation of variable refrigerant flow systems performance
Lee, Je Hyeon; Im, Piljae; Song, Young-hak
2017-10-24
Our study aims to compare the performance of a Variable Refrigerant Flow (VRF) system with a Roof Top Unit, (RTU) and a variable-air-volume (VAV) system through field tests and energy simulations. The field test was conducted in as similar conditions as possible between the two systems, such as the installation and operating environments of heating, the ventilation and air conditioning (HVAC) system, including internal heat gain and outdoor conditions, including buildings to compare the performance of the two systems accurately. A VRF system and RTU were installed at the test building located in Oak Ridge, Tennessee, in the USA. Themore » same internal heat gain was generated at the same operating time of the two systems using lighting, electric heaters, and humidifiers inside the building. The HVAC system was alternately operated between cooling and heating operations to acquire energy performance data and to compare energy usage. Furthermore, an hourly building energy simulation model was developed with regard to the VRF system and RTU, and then the model was calibrated using actual measured data. Then, annual energy consumption of the two systems were compared and analyzed using the calibrated model. Moreover, additional analysis was conducted when the controlled discharge air temperature in the RTU was changed. The field test result showed that when energy consumptions of two systems were compared at the same outdoor conditions, using the weather-normalized model, the VRF system exhibited an energy reduction of approximately 17% during cooling operation and of approximately 74% during heating operations. A comparison on the annual energy consumption using simulations showed that the VRF system reduced energy consumption more than that of the RTU by 60%. Furthermore, when the discharge air temperature in the RTU was controlled according to the outdoor air temperature, energy consumption of the RTU was reduced by 6% in cooling operations and by 18% in heating operation. As a result, energy consumption of the VRF system was reduced by more than that of the RTU by 55% approximately.« less
Field test and simulation evaluation of variable refrigerant flow systems performance
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, Je Hyeon; Im, Piljae; Song, Young-hak
Our study aims to compare the performance of a Variable Refrigerant Flow (VRF) system with a Roof Top Unit, (RTU) and a variable-air-volume (VAV) system through field tests and energy simulations. The field test was conducted in as similar conditions as possible between the two systems, such as the installation and operating environments of heating, the ventilation and air conditioning (HVAC) system, including internal heat gain and outdoor conditions, including buildings to compare the performance of the two systems accurately. A VRF system and RTU were installed at the test building located in Oak Ridge, Tennessee, in the USA. Themore » same internal heat gain was generated at the same operating time of the two systems using lighting, electric heaters, and humidifiers inside the building. The HVAC system was alternately operated between cooling and heating operations to acquire energy performance data and to compare energy usage. Furthermore, an hourly building energy simulation model was developed with regard to the VRF system and RTU, and then the model was calibrated using actual measured data. Then, annual energy consumption of the two systems were compared and analyzed using the calibrated model. Moreover, additional analysis was conducted when the controlled discharge air temperature in the RTU was changed. The field test result showed that when energy consumptions of two systems were compared at the same outdoor conditions, using the weather-normalized model, the VRF system exhibited an energy reduction of approximately 17% during cooling operation and of approximately 74% during heating operations. A comparison on the annual energy consumption using simulations showed that the VRF system reduced energy consumption more than that of the RTU by 60%. Furthermore, when the discharge air temperature in the RTU was controlled according to the outdoor air temperature, energy consumption of the RTU was reduced by 6% in cooling operations and by 18% in heating operation. As a result, energy consumption of the VRF system was reduced by more than that of the RTU by 55% approximately.« less
PTP1B inhibitor promotes endothelial cell motility by activating the DOCK180/Rac1 pathway.
Wang, Yuan; Yan, Feng; Ye, Qing; Wu, Xiao; Jiang, Fan
2016-04-07
Promoting endothelial cell (EC) migration is important not only for therapeutic angiogenesis, but also for accelerating re-endothelialization after vessel injury. Several recent studies have shown that inhibition of protein tyrosine phosphatase 1B (PTP1B) may promote EC migration and angiogenesis by enhancing the vascular endothelial growth factor receptor-2 (VEGFR2) signalling. In the present study, we demonstrated that PTP1B inhibitor could promote EC adhesion, spreading and migration, which were abolished by the inhibitor of Rac1 but not RhoA GTPase. PTP1B inhibitor significantly increased phosphorylation of p130Cas, and the interactions among p130Cas, Crk and DOCK180; whereas the phosphorylation levels of focal adhesion kinase, Src, paxillin, or Vav2 were unchanged. Gene silencing of DOCK180, but not Vav2, abrogated the effects of PTP1B inhibitor on EC motility. The effects of PTP1B inhibitor on EC motility and p130Cas/DOCK180 activation persisted in the presence of the VEGFR2 antagonist. In conclusion, we suggest that stimulation of the DOCK180 pathway represents an alternative mechanism of PTP1B inhibitor-stimulated EC motility, which does not require concomitant VEGFR2 activation as a prerequisite. Therefore, PTP1B inhibitor may be a useful therapeutic strategy for promoting EC migration in cardiovascular patients in which the VEGF/VEGFR functions are compromised.
NASA Astrophysics Data System (ADS)
Zhu, Na
This thesis presents an overview of the previous research work on dynamic characteristics and energy performance of buildings due to the integration of PCMs. The research work on dynamic characteristics and energy performance of buildings using PCMs both with and without air-conditioning is reviewed. Since the particular interest in using PCMs for free cooling and peak load shifting, specific research efforts on both subjects are reviewed separately. A simplified physical dynamic model of building structures integrated with SSPCM (shaped-stabilized phase change material) is developed and validated in this study. The simplified physical model represents the wall by 3 resistances and 2 capacitances and the PCM layer by 4 resistances and 2 capacitances respectively while the key issue is the parameter identification of the model. This thesis also presents the studies on the thermodynamic characteristics of buildings enhanced by PCM and on the investigation of the impacts of PCM on the building cooling load and peak cooling demand at different climates and seasons as well as the optimal operation and control strategies to reduce the energy consumption and energy cost by reducing the air-conditioning energy consumption and peak load. An office building floor with typical variable air volume (VAV) air-conditioning system is used and simulated as the reference building in the comparison study. The envelopes of the studied building are further enhanced by integrating the PCM layers. The building system is tested in two selected cities of typical climates in China including Hong Kong and Beijing. The cold charge and discharge processes, the operation and control strategies of night ventilation and the air temperature set-point reset strategy for minimizing the energy consumption and electricity cost are studied. This thesis presents the simulation test platform, the test results on the cold storage and discharge processes, the air-conditioning energy consumption and demand reduction potentials in typical air-conditioning seasons in typical China cites as well as the impacts of operation and control strategies.
Kim, Hun Sik; Long, Eric O.
2013-01-01
The cytotoxic effects of natural killer (NK) cells and their ability to secrete cytokines require the induction of synergistic signals from co-activation receptors, such as CD314 (NKG2D) and CD244 (2B4), which bind to ligands expressed on target cells. Synergy is required to overcome inhibition of the guanine nucleotide exchange factor (GEF) Vav1, a central regulator of NK cell activation, by the E3 ubiquitin ligase c-Cbl. However, the molecular basis for this synergy is unknown. Here, we showed that the adaptor protein Src homology 2 (SH2) domain–containing leukocyte phosphoprotein of 76 kD (SLP-76) was required for this synergy, and that distinct tyrosine residues in SLP-76 were phosphorylated by each receptor of a synergistic pair. Selective phosphorylation of tyrosine 113 or tyrosine 128 in SLP-76, each of which enables binding of SLP-76 to Vav1, was unique to receptors that stimulate ligand-dependent target cell killing, because antibody-dependent stimulation by Fc receptor CD16 promoted phosphorylation at both sites. Knockdown and reconstitution experiments with SLP-76 showed the distinct role of each tyrosine in the synergistic mobilization of Ca2+, revealing an unexpected degree of selectivity in the phosphorylation of SLP-76 by NK cell co-activation receptors. Together, these data suggest that complementation of separate phospho-tyrosine targets in SLP-76 forms the basis of synergistic NK cell activation. PMID:22786724
Kim, Hun Sik; Long, Eric O
2012-07-10
The cytotoxic effects of natural killer (NK) cells and their ability to secrete cytokines require synergistic signals from specific pairs of co-activation receptors, such as CD314 (also known as NKG2D) and CD244 (2B4), which bind to distinct ligands present on target cells. These signals are required to overcome inhibition mediated by the E3 ubiquitin ligase c-Cbl of the guanine nucleotide exchange factor Vav1, which promotes activation of NK cells. Here, we showed that the adaptor protein SLP-76 (Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons) was required for this synergy and that distinct tyrosine residues in SLP-76 were phosphorylated by each member of a pair of synergistic receptors. Selective phosphorylation of tyrosine 113 or tyrosine 128 in SLP-76 enabled binding of SLP-76 to Vav1. Selective phosphorylation of SLP-76 at these residues was restricted to receptors that stimulated ligand-dependent target cell killing; antibody-dependent stimulation of the Fc receptor CD16 promoted phosphorylation at both sites. Knockdown and reconstitution experiments with SLP-76 mutant proteins showed the distinct role of each tyrosine in the synergistic mobilization of Ca2+, revealing an unexpected degree of selectivity in the phosphorylation of SLP-76 by NK cell co-activation receptors. Together, these data suggest that combined phosphorylation of separate tyrosine residues in SLP-76 forms the basis of synergistic NK cell activation.
Lifelong haematopoiesis is established by hundreds of precursors throughout mammalian ontogeny.
Ganuza, Miguel; Hall, Trent; Finkelstein, David; Chabot, Ashley; Kang, Guolian; McKinney-Freeman, Shannon
2017-10-01
Current dogma asserts that mammalian lifelong blood production is established by a small number of blood progenitors. However, this model is based on assays that require the disruption, transplantation and/or culture of embryonic tissues. Here, we used the sample-to-sample variance of a multicoloured lineage trace reporter to assess the frequency of emerging lifelong blood progenitors while avoiding the disruption, culture or transplantation of embryos. We find that approximately 719 Flk1 + mesodermal precursors, 633 VE-cadherin + endothelial precursors and 545 Vav1 + nascent blood stem and progenitor cells emerge to establish the haematopoietic system at embryonic days (E)7-E8.5, E8.5-E11.5 and E11.5-E14.5, respectively. We also determined that the spatio-temporal recruitment of endothelial blood precursors begins at E8.5 and ends by E10.5, and that many c-Kit + clusters of newly specified blood progenitors in the aorta are polyclonal in origin. Our work illuminates the dynamics of the developing mammalian blood system during homeostasis.
Building Energy Management Open Source Software
DOE Office of Scientific and Technical Information (OSTI.GOV)
This is the repository for Building Energy Management Open Source Software (BEMOSS), which is an open source operating system that is engineered to improve sensing and control of equipment in small- and medium-sized commercial buildings. BEMOSS offers the following key features: (1) Open source, open architecture – BEMOSS is an open source operating system that is built upon VOLTTRON – a distributed agent platform developed by Pacific Northwest National Laboratory (PNNL). BEMOSS was designed to make it easy for hardware manufacturers to seamlessly interface their devices with BEMOSS. Software developers can also contribute to adding additional BEMOSS functionalities and applications.more » (2) Plug & play – BEMOSS was designed to automatically discover supported load controllers (including smart thermostats, VAV/RTUs, lighting load controllers and plug load controllers) in commercial buildings. (3) Interoperability – BEMOSS was designed to work with load control devices form different manufacturers that operate on different communication technologies and data exchange protocols. (4) Cost effectiveness – Implementation of BEMOSS deemed to be cost-effective as it was built upon a robust open source platform that can operate on a low-cost single-board computer, such as Odroid. This feature could contribute to its rapid deployment in small- or medium-sized commercial buildings. (5) Scalability and ease of deployment – With its multi-node architecture, BEMOSS provides a distributed architecture where load controllers in a multi-floor and high occupancy building could be monitored and controlled by multiple single-board computers hosting BEMOSS. This makes it possible for a building engineer to deploy BEMOSS in one zone of a building, be comfortable with its operation, and later on expand the deployment to the entire building to make it more energy efficient. (6) Ability to provide local and remote monitoring – BEMOSS provides both local and remote monitoring ability with role-based access control. (7) Security – In addition to built-in security features provided by VOLTTRON, BEMOSS provides enhanced security features, including BEMOSS discovery approval process, encrypted core-to-node communication, thermostat anti-tampering feature and many more. (8) Support from the Advisory Committee – BEMOSS was developed in consultation with an advisory committee from the beginning of the project. BEMOSS advisory committee comprises representatives from 22 organizations from government and industry.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Liping; Hong, Tianzhen
Almost half of the total energy used in the U.S. buildings is consumed by heating, ventilation and air conditionings (HVAC) according to EIA statistics. Among various driving factors to energy performance of building, operations and maintenance play a significant role. Many researches have been done to look at design efficiencies and operational controls for improving energy performance of buildings, but very few study the impacts of HVAC systems maintenance. Different practices of HVAC system maintenance can result in substantial differences in building energy use. If a piece of HVAC equipment is not well maintained, its performance will degrade. If sensorsmore » used for control purpose are not calibrated, not only building energy usage could be dramatically increased, but also mechanical systems may not be able to satisfy indoor thermal comfort. Properly maintained HVAC systems can operate efficiently, improve occupant comfort, and prolong equipment service life. In the paper, maintenance practices for HVAC systems are presented based on literature reviews and discussions with HVAC engineers, building operators, facility managers, and commissioning agents. We categorize the maintenance practices into three levels depending on the maintenance effort and coverage: 1) proactive, performance-monitored maintenance; 2) preventive, scheduled maintenance; and 3) reactive, unplanned or no maintenance. A sampled list of maintenance issues, including cooling tower fouling, boiler/chiller fouling, refrigerant over or under charge, temperature sensor offset, outdoor air damper leakage, outdoor air screen blockage, outdoor air damper stuck at fully open position, and dirty filters are investigated in this study using field survey data and detailed simulation models. The energy impacts of both individual maintenance issue and combined scenarios for an office building with central VAV systems and central plant were evaluated by EnergyPlus simulations using three approaches: 1) direct modeling with EnergyPlus, 2) using the energy management system feature of EnergyPlus, and 3) modifying EnergyPlus source code. The results demonstrated the importance of maintenance for HVAC systems on energy performance of buildings. The research is intended to provide a guideline to help practitioners and building operators to gain the knowledge of maintaining HVAC systems in efficient operations, and prioritize HVAC maintenance work plan. The paper also discusses challenges of modeling building maintenance issues using energy simulation programs.« less
CD94/NKG2A inhibits NK cell activation by disrupting the actin network at the immunological synapse.
Masilamani, Madhan; Nguyen, Connie; Kabat, Juraj; Borrego, Francisco; Coligan, John E
2006-09-15
An adequate immune response is the result of the fine balance between activation and inhibitory signals. The exact means by which inhibitory signals obviate activation signals in immune cells are not totally elucidated. Human CD94/NKG2A is an ITIM-containing inhibitory receptor expressed by NK cells and some CD8+ T cells that recognize HLA-E. We show that the engagement of this receptor prevents NK cell activation by disruption of the actin network and exclusion of lipid rafts at the point of contact with its ligand (inhibitory NK cell immunological synapse, iNKIS). CD94/NKG2A engagement leads to recruitment and activation of src homology 2 domain-bearing tyrosine phosphatase 1. This likely explains the observed dephosphorylation of guanine nucleotide exchange factor and regulator of actin, Vav1, as well as ezrin-radixin-moesin proteins that connect actin filaments to membrane structures. In contrast, NK cell activation by NKG2D induced Vav1 and ezrin-radixin-moesin phosphorylation. Thus, CD94/NKG2A prevents actin-dependent recruitment of raft-associated activation receptors complexes to the activating synapse. This was further substantiated by showing that inhibition of actin polymerization abolished lipid rafts exclusion at the iNKIS, whereas cholesterol depletion had no effect on actin disruption at the iNKIS. These data indicate that the lipid rafts exclusion at the iNKIS is an active process which requires an intact cytoskeleton to maintain lipid rafts outside the inhibitory synapse. The net effect is to maintain an inhibitory state in the proximity of the iNKIS, while allowing the formation of activation synapse at distal points within the same NK cell.
CD25 and CD69 induction by α4β1 outside-in signalling requires TCR early signalling complex proteins
Cimo, Ann-Marie; Ahmed, Zamal; McIntyre, Bradley W.; Lewis, Dorothy E.; Ladbury, John E.
2013-01-01
Distinct signalling pathways producing diverse cellular outcomes can utilize similar subsets of proteins. For example, proteins from the TCR (T-cell receptor) ESC (early signalling complex) are also involved in interferon-α receptor signalling. Defining the mechanism for how these proteins function within a given pathway is important in understanding the integration and communication of signalling networks with one another. We investigated the contributions of the TCR ESC proteins Lck (lymphocyte-specific kinase), ZAP-70 (ζ-chain-associated protein of 70 kDa), Vav1, SLP-76 [SH2 (Src homology 2)-domain-containing leukocyte protein of 76 kDa] and LAT (linker for activation of T-cells) to integrin outside-in signalling in human T-cells. Lck, ZAP-70, SLP-76, Vav1 and LAT were activated by α4β1 outside-in signalling, but in a manner different from TCR signalling. TCR stimulation recruits ESC proteins to activate the mitogen-activated protein kinase ERK (extracellular-signal-regulated kinase). α4β1 outside-in-mediated ERK activation did not require TCR ESC proteins. However, α4β1 outside-in signalling induced CD25 and co-stimulated CD69 and this was dependent on TCR ESC proteins. TCR and α4β1 outside-in signalling are integrated through the common use of TCR ESC proteins; however, these proteins display functionally distinct roles in these pathways. These novel insights into the cross-talk between integrin outside-in and TCR signalling pathways are highly relevant to the development of therapeutic strategies to overcome disease associated with T-cell deregulation. PMID:23758320
Ugarelli, Rita; Kristensen, Stig Morten; Røstum, Jon; Saegrov, Sveinung; Di Federico, Vittorio
2009-01-01
Oslo Vann og Avløpsetaten (Oslo VAV)-the water/wastewater utility in the Norwegian capital city of Oslo-is assessing future strategies for selection of most reliable materials for wastewater networks, taking into account not only material technical performance but also material performance, regarding operational condition of the system.The research project undertaken by SINTEF Group, the largest research organisation in Scandinavia, NTNU (Norges Teknisk-Naturvitenskapelige Universitet) and Oslo VAV adopts several approaches to understand reasons for failures that may impact flow capacity, by analysing historical data for blockages in Oslo.The aim of the study was to understand whether there is a relationship between the performance of the pipeline and a number of specific attributes such as age, material, diameter, to name a few. This paper presents the characteristics of the data set available and discusses the results obtained by performing two different approaches: a traditional statistical analysis by segregating the pipes into classes, each of which with the same explanatory variables, and a Evolutionary Polynomial Regression model (EPR), developed by Technical University of Bari and University of Exeter, to identify possible influence of pipe's attributes on the total amount of predicted blockages in a period of time.Starting from a detailed analysis of the available data for the blockage events, the most important variables are identified and a classification scheme is adopted.From the statistical analysis, it can be stated that age, size and function do seem to have a marked influence on the proneness of a pipeline to blockages, but, for the reduced sample available, it is difficult to say which variable it is more influencing. If we look at total number of blockages the oldest class seems to be the most prone to blockages, but looking at blockage rates (number of blockages per km per year), then it is the youngest class showing the highest blockage rate. EPR allowed identifying the relation between attitude to block and pipe's attributes in order to understand what affects the possibility to have a blockage in the pipe. EPR provides formulae to compute the accumulated number of blockages for a pipe class at the end of a given period of time. Those formulae do not represent simply regression models but highlight those variables which affect the physical phenomenon in question.
An Effective Model of the Retinoic Acid Induced HL-60 Differentiation Program.
Tasseff, Ryan; Jensen, Holly A; Congleton, Johanna; Dai, David; Rogers, Katharine V; Sagar, Adithya; Bunaciu, Rodica P; Yen, Andrew; Varner, Jeffrey D
2017-10-30
In this study, we present an effective model All-Trans Retinoic Acid (ATRA)-induced differentiation of HL-60 cells. The model describes reinforcing feedback between an ATRA-inducible signalsome complex involving many proteins including Vav1, a guanine nucleotide exchange factor, and the activation of the mitogen activated protein kinase (MAPK) cascade. We decomposed the effective model into three modules; a signal initiation module that sensed and transformed an ATRA signal into program activation signals; a signal integration module that controlled the expression of upstream transcription factors; and a phenotype module which encoded the expression of functional differentiation markers from the ATRA-inducible transcription factors. We identified an ensemble of effective model parameters using measurements taken from ATRA-induced HL-60 cells. Using these parameters, model analysis predicted that MAPK activation was bistable as a function of ATRA exposure. Conformational experiments supported ATRA-induced bistability. Additionally, the model captured intermediate and phenotypic gene expression data. Knockout analysis suggested Gfi-1 and PPARg were critical to the ATRAinduced differentiation program. These findings, combined with other literature evidence, suggested that reinforcing feedback is central to hyperactive signaling in a diversity of cell fate programs.
A critical role for the regulation of Syk from agglutination to aggregation in human platelets.
Shih, Chun-Ho; Chiang, Tin-Bin; Wang, Wen-Jeng
2014-01-10
Agglucetin, a tetrameric glycoprotein (GP) Ibα agonist from Formosan Agkistrodon acutus venom, has been characterized as an agglutination inducer in human washed platelets (WPs). In platelet-rich plasma (PRP), agglucetin dramatically elicits a biphasic response of agglutination and subsequent aggregation. For clarifying the intracellular signaling events from agglutination to aggregation in human platelets, we examined the essential signaling molecules involved through the detection of protein tyrosine phosphorylation (PTP). In WPs, an anti-GPIbα monoclonal antibody (mAb) AP1, but not a Src kinase inhibitor PP1, completely inhibited agglucetin-induced agglutination. However, PP1 but not AP1 had a potent suppression on platelet aggregation by a GPVI activator convulxin. The PTP analyses showed agglucetin alone can cause a weak pattern involving sequential phosphorylation of Lyn/Fyn, Syk, SLP-76 and phospholipase Cγ2 (PLCγ2). Furthermore, a Syk-selective kinase inhibitor, piceatannol, significantly suppressed the aggregating response in agglucetin-activated PRP. Analyzed by flow cytometry, the binding capacity of fluorophore-conjugated PAC-1, a mAb recognizing activated integrin αIIbβ3, was shown to increase in agglucetin-stimulated platelets. Again, piceatannol but not PP1 had a concentration-dependent suppression on agglucetin-induced αIIbβ3 exposure. Moreover, the formation of signalosome, including Syk, SLP-76, VAV, adhesion and degranulation promoting adapter protein (ADAP) and PLCγ2, are required for platelet aggregation in agglucetin/fibrinogen-activated platelets. In addition, GPIbα-ligation via agglucetin can substantially promote the interactions between αIIbβ3 and fibrinogen. Therefore, the signal pathway of Lyn/Fyn/Syk/SLP-76/ADAP/VAV/PLCγ2/PKC is sufficient to trigger platelet aggregation in agglucetin/fibrinogen-pretreated platelets. Importantly, Syk may function as a major regulator for the response from GPIbα-initiated agglutination to integrin αIIbβ3-dependent aggregation in human platelets. Copyright © 2013 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Im, Piljae; Liu, Xiaobing
High initial costs and lack of public awareness of ground-source heat pump (GSHP) technology are the two major barriers preventing rapid deployment of this energy-saving technology in the United States. Under the American Recovery and Reinvestment Act (ARRA), 26 GSHP projects were competitively selected and carried out to demonstrate the benefits of GSHP systems and innovative technologies for cost reduction and/or performance improvement. This report highlights the findings of a case study of one such GSHP demonstration projects that uses a recycled water heat pump (RWHP) system installed at the Denver Museum of Nature & Science in Denver, Colorado. Themore » RWHP system uses recycled water from the city’s water system as the heat sink and source for a modular water-to-water heat pump (WWHP). This case study was conducted based on the available measured performance data from December 2014 through August 2015, utility bills of the building in 2014 and 2015, construction drawings, maintenance records, personal communications, and construction costs. The annual energy consumption of the RWHP system was calculated based on the available measured data and other related information. It was compared with the performance of a baseline scenario— a conventional VAV system using a water-cooled chiller and a natural gas fired boiler, both of which have the minimum energy efficiencies allowed by ASHRAE 90.1-2010. The comparison was made to determine energy savings, operating cost savings, and CO2 emission reductions achieved by the RWHP system. A cost analysis was performed to evaluate the simple payback of the RWHP system. Summarized below are the results of the performance analysis, the learned lessons, and recommended improvement in the operation of the RWHP system.« less
Retinoic Acid Therapy Resistance Progresses from Unilineage to Bilineage in HL-60 Leukemic Blasts
Jensen, Holly A.; Bunaciu, Rodica P.; Ibabao, Christopher N.; Myers, Rebecca; Varner, Jeffrey D.; Yen, Andrew
2014-01-01
Emergent resistance can be progressive and driven by global signaling aberrations. All-trans retinoic acid (RA) is the standard therapeutic agent for acute promyelocytic leukemia, but 10–20% of patients are not responsive, and initially responsive patients relapse and develop retinoic acid resistance. The patient-derived, lineage-bipotent acute myeloblastic leukemia (FAB M2) HL-60 cell line is a potent tool for characterizing differentiation-induction therapy responsiveness and resistance in t(15;17)-negative cells. Wild-type (WT) HL-60 cells undergo RA-induced granulocytic differentiation, or monocytic differentiation in response to 1,25-dihydroxyvitamin D3 (D3). Two sequentially emergent RA-resistant HL-60 cell lines, R38+ and R38-, distinguishable by RA-inducible CD38 expression, do not arrest in G1/G0 and fail to upregulate CD11b and the myeloid-associated signaling factors Vav1, c-Cbl, Lyn, Fgr, and c-Raf after RA treatment. Here, we show that the R38+ and R38- HL-60 cell lines display a progressive reduced response to D3-induced differentiation therapy. Exploiting the biphasic dynamic of induced HL-60 differentiation, we examined if resistance-related defects occurred during the first 24 h (the early or “precommitment” phase) or subsequently (the late or “lineage-commitment” phase). HL-60 were treated with RA or D3 for 24 h, washed and retreated with either the same, different, or no differentiation agent. Using flow cytometry, D3 was able to induce CD38, CD11b and CD14 expression, and G1/G0 arrest when present during the lineage-commitment stage in R38+ cells, and to a lesser degree in R38- cells. Clustering analysis of cytometry and quantified Western blot data indicated that WT, R38+ and R38- HL-60 cells exhibited decreasing correlation between phenotypic markers and signaling factor expression. Thus differentiation induction therapy resistance can develop in stages, with initial partial RA resistance and moderate vitamin D3 responsiveness (unilineage maturation block), followed by bilineage maturation block and progressive signaling defects, notably the reduced expression of Vav1, Fgr, and c-Raf. PMID:24922062
Geographical distribution of genetic diversity in Secale landrace and wild accessions.
Hagenblad, Jenny; Oliveira, Hugo R; Forsberg, Nils E G; Leino, Matti W
2016-01-19
Rye, Secale cereale L., has historically been a crop of major importance and is still a key cereal in many parts of Europe. Single populations of cultivated rye have been shown to capture a large proportion of the genetic diversity present in the species, but the distribution of genetic diversity in subspecies and across geographical areas is largely unknown. Here we explore the structure of genetic diversity in landrace rye and relate it to that of wild and feral relatives. A total of 567 SNPs were analysed in 434 individuals from 76 accessions of wild, feral and cultivated rye. Genetic diversity was highest in cultivated rye, slightly lower in feral rye taxa and significantly lower in the wild S. strictum Presl. and S. africanum Stapf. Evaluation of effects from ascertainment bias suggests underestimation of diversity primarily in S. strictum and S. africanum. Levels of ascertainment bias, STRUCTURE and principal component analyses all supported the proposed classification of S. africanum and S. strictum as a separate species from S. cereale. S. afghanicum (Vav.) Roshev, S. ancestrale Zhuk., S. dighoricum (Vav.) Roshev, S. segetale (Zhuk.) Roshev and S. vavilovii Grossh. seemed, in contrast, to share the same gene pool as S. cereale and their genetic clustering was more dependent on geographical origin than taxonomic classification. S. vavilovii was found to be the most likely wild ancestor of cultivated rye. Among cultivated rye landraces from Europe, Asia and North Africa five geographically discrete genetic clusters were identified. These had only limited overlap with major agro-climatic zones. Slash-and-burn rye from the Finnmark area in Scandinavia formed a distinct cluster with little similarity to other landrace ryes. Regional studies of Northern and South-West Europe demonstrate different genetic distribution patterns as a result of varying cultivation intensity. With the exception of S. strictum and S. africanum different rye taxa share the majority of the genetic variation. Due to the vast sharing of genetic diversity within the S. cereale clade, ascertainment bias seems to be a lesser problem in rye than in predominantly selfing species. By exploiting within accession diversity geographic structure can be shown on a much finer scale than previously reported.
Distinct Brca1 Mutations Differentially Reduce Hematopoietic Stem Cell Function.
Mgbemena, Victoria E; Signer, Robert A J; Wijayatunge, Ranjula; Laxson, Travis; Morrison, Sean J; Ross, Theodora S
2017-01-24
BRCA1 is a well-known DNA repair pathway component and a tissue-specific tumor suppressor. However, its role in hematopoiesis is uncertain. Here, we report that a cohort of patients heterozygous for BRCA1 mutations experienced more hematopoietic toxicity from chemotherapy than those with BRCA2 mutations. To test whether this reflects a requirement for BRCA1 in hematopoiesis, we generated mice with Brca1 mutations in hematopoietic cells. Mice homozygous for a null Brca1 mutation in the embryonic hematopoietic system (Vav1-iCre;Brca1 F22-24/F22-24 ) developed hematopoietic defects in early adulthood that included reduced hematopoietic stem cells (HSCs). Although mice homozygous for a huBRCA1 knockin allele (Brca1 BRCA1/BRCA1 ) were normal, mice with a mutant huBRCA1/5382insC allele and a null allele (Mx1-Cre;Brca1 F22-24/5382insC ) had severe hematopoietic defects marked by a complete loss of hematopoietic stem and progenitor cells. Our data show that Brca1 is necessary for HSC maintenance and normal hematopoiesis and that distinct mutations lead to different degrees of hematopoietic dysfunction. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
Arsenault, Patrick R.; Pei, Fei; Lee, Rebecca; Kerestes, Heddy; Percy, Melanie J.; Keith, Brian; Simon, M. Celeste; Lappin, Terence R. J.; Khurana, Tejvir S.; Lee, Frank S.
2013-01-01
The central pathway for controlling red cell mass is the PHD (prolyl hydroxylase domain protein):hypoxia-inducible factor (HIF) pathway. HIF, which is negatively regulated by PHD, activates numerous genes, including ones involved in erythropoiesis, such as the ERYTHROPOIETIN (EPO) gene. Recent studies have implicated PHD2 as the key PHD isoform regulating red cell mass. Studies of humans have identified erythrocytosis-associated, heterozygous point mutations in the PHD2 gene. A key question concerns the mechanism by which human mutations lead to phenotypes. In the present report, we generated and characterized a mouse line in which a P294R knock-in mutation has been introduced into the mouse Phd2 locus to model the first reported human PHD2 mutation (P317R). Phd2P294R/+ mice display a degree of erythrocytosis equivalent to that seen in Phd2+/− mice. The Phd2P294R/+-associated erythrocytosis is reversed in a Hif2a+/−, but not a Hif1a+/− background. Additional studies using various conditional knock-outs of Phd2 reveal that erythrocytosis can be induced by homozygous and heterozygous knock-out of Phd2 in renal cortical interstitial cells using a Pax3-Cre transgene or by homozygous knock-out of Phd2 in hematopoietic progenitors driven by a Vav1-Cre transgene. These studies formally prove that a missense mutation in PHD2 is the cause of the erythrocytosis, show that this occurs through haploinsufficiency, and point to multifactorial control of red cell mass by PHD2. PMID:24121508
Maruvada, Ravi
2012-01-01
Meningitis-causing Escherichia coli K1 internalization of the blood-brain barrier is required for penetration into the brain, but the host-microbial interactions involved in E. coli entry of the blood-brain barrier remain incompletely understood. We show here that a meningitis-causing E. coli K1 strain RS218 activates Rac1 (GTP-Rac1) of human brain microvascular endothelial cells (HBMEC) in a time-dependent manner. Both activation and bacterial invasion were significantly inhibited in the presence of a Rac1 inhibitor. We further showed that the guanine nucleotide exchange factor Vav2, not β-Pix, was involved in E. coli K1-mediated Rac1 activation. Since activated STAT3 is known to bind GTP-Rac1, the relationship between STAT3 and Rac1 was examined in E. coli K1 invasion of HBMEC. Downregulation of STAT3 resulted in significantly decreased E. coli invasion compared to control HBMEC, as well as a corresponding decrease in GTP-Rac1, suggesting that Rac1 activation in response to E. coli is under the control of STAT3. More importantly, two E. coli determinants contributing to HBMEC invasion, IbeA and OmpA, were shown to affect both Rac1 activation and their association with STAT3. These findings demonstrate for the first time that specific E. coli determinants regulate a novel mechanism of STAT3 cross talk with Rac1 in E. coli K1 invasion of HBMEC. PMID:22451524
Maruvada, Ravi; Kim, Kwang Sik
2012-06-01
Meningitis-causing Escherichia coli K1 internalization of the blood-brain barrier is required for penetration into the brain, but the host-microbial interactions involved in E. coli entry of the blood-brain barrier remain incompletely understood. We show here that a meningitis-causing E. coli K1 strain RS218 activates Rac1 (GTP-Rac1) of human brain microvascular endothelial cells (HBMEC) in a time-dependent manner. Both activation and bacterial invasion were significantly inhibited in the presence of a Rac1 inhibitor. We further showed that the guanine nucleotide exchange factor Vav2, not β-Pix, was involved in E. coli K1-mediated Rac1 activation. Since activated STAT3 is known to bind GTP-Rac1, the relationship between STAT3 and Rac1 was examined in E. coli K1 invasion of HBMEC. Downregulation of STAT3 resulted in significantly decreased E. coli invasion compared to control HBMEC, as well as a corresponding decrease in GTP-Rac1, suggesting that Rac1 activation in response to E. coli is under the control of STAT3. More importantly, two E. coli determinants contributing to HBMEC invasion, IbeA and OmpA, were shown to affect both Rac1 activation and their association with STAT3. These findings demonstrate for the first time that specific E. coli determinants regulate a novel mechanism of STAT3 cross talk with Rac1 in E. coli K1 invasion of HBMEC.
Kirabo, Annet; Park, Sung O.; Wamsley, Heather L.; Gali, Meghanath; Baskin, Rebekah; Reinhard, Mary K.; Zhao, Zhizhuang J.; Bisht, Kirpal S.; Keserű, György M.; Cogle, Christopher R.; Sayeski, Peter P.
2013-01-01
Philadelphia chromosome–negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocytosis, and myelofibrosis, are disorders characterized by abnormal hematopoiesis. Among these myeloproliferative neoplasms, myelofibrosis has the most unfavorable prognosis. Furthermore, currently available therapies for myelofibrosis have little to no efficacy in the bone marrow and hence, are palliative. We recently developed a Janus kinase 2 (Jak2) small molecule inhibitor called G6 and found that it exhibits marked efficacy in a xenograft model of Jak2-V617F–mediated hyperplasia and a transgenic mouse model of Jak2-V617F–mediated polycythemia vera/essential thrombocytosis. However, its efficacy in Jak2-mediated myelofibrosis has not previously been examined. Here, we hypothesized that G6 would be efficacious in Jak2-V617F–mediated myelofibrosis. To test this, mice expressing the human Jak2-V617F cDNA under the control of the vav promoter were administered G6 or vehicle control solution, and efficacy was determined by measuring parameters within the peripheral blood, liver, spleen, and bone marrow. We found that G6 significantly reduced extramedullary hematopoiesis in the liver and splenomegaly. In the bone marrow, G6 significantly reduced pathogenic Jak/STAT signaling by 53%, megakaryocytic hyperplasia by 70%, and the Jak2 mutant burden by 68%. Furthermore, G6 significantly improved the myeloid to erythroid ratio and significantly reversed the myelofibrosis. Collectively, these results indicate that G6 is efficacious in Jak2-V617F–mediated myelofibrosis, and given its bone marrow efficacy, it may alter the natural history of this disease. PMID:22796437
Valerio, Daria G.; Xu, Haiming; Eisold, Meghan E.; Woolthuis, Carolien M.; Pandita, Tej K.
2017-01-01
K(lysine) acetyltransferase 8 (KAT8, also known as MOF) mediates the acetylation of histone H4 at lysine 16 (H4K16ac) and is crucial for murine embryogenesis. Lysine acetyltransferases have been shown to regulate various stages of normal hematopoiesis. However, the function of MOF in hematopoietic stem cell (HSC) development has not yet been elucidated. We set out to study the role of MOF in general hematopoiesis by using a Vav1-cre–induced conditional murine Mof knockout system and found that MOF is critical for hematopoietic cell maintenance and HSC engraftment capacity in adult hematopoiesis. Rescue experiments with a MOF histone acetyltransferase domain mutant illustrated the requirement for MOF acetyltransferase activity in the clonogenic capacity of HSCs and progenitors. In stark contrast, fetal steady-state hematopoiesis at embryonic day (E) 14.5 was not affected by homozygous Mof deletion despite dramatic loss of global H4K16ac. Hematopoietic defects start manifesting in late gestation at E17.5. The discovery that MOF and its H4K16ac activity are required for adult but not early and midgestational hematopoiesis supports the notion that multiple chromatin regulators may be crucial for hematopoiesis at varying stages of development. MOF is therefore a developmental-stage–specific chromatin regulator found to be essential for adult but not early fetal hematopoiesis. PMID:27827827
Chen, Rong; Sung, Wen-Pei; Chang, Hung-Chang; Chi, Yi-Rou
2013-01-01
A human life demand set to emerge in the future is the achievement of sustainability by maintaining a comfortable indoor environment without excessive reliance on energy-consuming air conditioners. The major research processes in this study are: (1) measuring indoor air quality and thermal comfort to evaluate the comfort of an indoor environment; (2) implementing questionnaire survey analysis to explore people's environmental self-perceptions and conducting a meta-analysis of the measurement results for air quality and physical aspects; and (3) constructing an indoor monitoring and management system. The experimental and analysis results of this research reveal that most of the office occupants preferred a cooler environment with a lower temperature. Additionally, because the summers in Taiwan are humid and hot, the occupants of an indoor space tend to feel uncomfortable because of the high humidity and poor indoor air quality. Therefore, Variable Air Volume (VAV), two air intakes, and exhaust plant are installed to improve indoor environment. After improvement, a lower temperature (approximately 21.2–23.9°C) indirectly reduces humidity, thereby making the occupants comfortable. Increasing air velocity to 0.1 ~ 0.15 m/s, the carbon dioxide concentrations decrease below the requirement of the WHO. Ninety-five percent of the workers corresponded to the standard comfort zone after this improvement. PMID:24311976
Law, Che-Leung; Ewings, Maria K.; Chaudhary, Preet M.; Solow, Sasha A.; Yun, Theodore J.; Marshall, Aaron J.; Hood, Leroy; Clark, Edward A.
1999-01-01
Propagation of signals from the T cell antigen receptor (TCR) involves a number of adaptor molecules. SH2 domain–containing protein 76 (SLP-76) interacts with the guanine nucleotide exchange factor Vav to activate the nuclear factor of activated cells (NF-AT), and its expression is required for normal T cell development. We report the cloning and characterization of a novel Grb2-like adaptor molecule designated as Grb2-related protein of the lymphoid system (GrpL). Expression of GrpL is restricted to hematopoietic tissues, and it is distinguished from Grb2 by having a proline-rich region. GrpL can be coimmunoprecipitated with SLP-76 but not with Sos1 or Sos2 from Jurkat cell lysates. In contrast, Grb2 can be coimmunoprecipitated with Sos1 and Sos2 but not with SLP-76. Moreover, tyrosine-phosphorylated LAT/pp36/38 in detergent lysates prepared from anti-CD3 stimulated T cells associated with Grb2 but not GrpL. These data reveal the presence of distinct complexes involving GrpL and Grb2 in T cells. A functional role of the GrpL–SLP-76 complex is suggested by the ability of GrpL to act alone or in concert with SLP-76 to augment NF-AT activation in Jurkat T cells. PMID:10209041
Rangelova, Svetla; Kirschnek, Susanne; Strasser, Andreas; Häcker, Georg
2008-01-01
Fas-associated protein with death domain/mediator of receptor induced toxicity (FADD/MORT1) was first described as a transducer of death receptor signalling but was later recognized also to be important for proliferation of T cells. B-cell lymphoma 3 (Bcl-3) is a relatively little understood member of the nuclear factor (NF)-κB family of transcription factors. We recently found that Bcl-3 is up-regulated in T cells from mice where FADD function is blocked by a dominant negative transgene (FADD-DN). To understand the importance of this, we generated FADD-DN/bcl-3−/− mice. Here, we report that T cells from these mice show massive cell death and severely reduced proliferation in response to T-cell receptor (TCR) stimulation in vitro. Transgenic co-expression of Bcl-2 (FADD-DN/bcl-3−/−/vav-bcl-2 mice) rescued the survival but not the proliferation of T cells. FADD-DN/bcl-3−/− mice had normal thymocyte numbers but reduced numbers of peripheral T cells despite an increase in cycling T cells in vivo. However, activation of the classical NF-κB and extracellular regulated kinase (ERK) pathways and expression of interleukin (IL)-2 mRNA upon stimulation were normal in T cells from FADD-DN/bcl-3−/− mice. These data suggest that FADD and Bcl-3 regulate separate pathways that both contribute to survival and proliferation in mouse T cells. PMID:18557791
NASA Technical Reports Server (NTRS)
Latorella, Kara A.
2015-01-01
Flightdeck Interval Management is one of the NextGen operational concepts that FAA is sponsoring to realize requisite National Airspace System (NAS) efficiencies. Interval Management will reduce variability in temporal deviations at a position, and thereby reduce buffers typically applied by controllers - resulting in higher arrival rates, and more efficient operations. Ground software generates a strategic schedule of aircraft pairs. Air Traffic Control (ATC) provides an IM clearance with the IM spacing objective (i.e., the TTF, and at which point to achieve the appropriate spacing from this aircraft) to the IM aircraft. Pilots must dial FIM speeds into the speed window on the Mode Control Panel in a timely manner, and attend to deviations between actual speed and the instantaneous FIM profile speed. Here, the crew is assumed to be operating the aircraft with autothrottles on, with autopilot engaged, and the autoflight system in Vertical Navigation (VNAV) and Lateral Navigation (LNAV); and is responsible for safely flying the aircraft while maintaining situation awareness of their ability to follow FIM speed commands and to achieve the FIM spacing goal. The objective of this study is to examine whether three Notification Methods and four Avionics Conditions affect pilots' performance, ratings on constructs associated with performance (workload, situation awareness), or opinions on acceptability. Three Notification Methods (alternate visual and aural alerts that notified pilots to the onset of a speed target, conformance deviation from the required speed profile, and reminded them if they failed to enter the speed within 10 seconds) were examined. These Notification Methods were: VVV (visuals for all three events), VAV (visuals for all three events, plus an aural for speed conformance deviations), and AAA (visual indications and the same aural to indicate all three of these events). Avionics Conditions were defined by the instrumentation (and location) used to present IM information to crews: (1) Integrated (IM information is embedded in extant PFD (Primary Flight Display), ND (Navigation Display), EICAS (Engine Indicating and Crew Alerting System) displays); (2) EFB_Aft (IM information is only supplied in an EFB and mounted in location similar to that for MITRE's UPS work); (3) EFB_Fore (IM information is only supplied in an EFB which is mounted more forward, under the side window), and (4) EFB_Aft plus use of an AGD (the same IM information is supplied in an EFB and on an AGD, both mounted in locations similar to that in MITRE's UPS work ). Twelve commercial pilot crews flew descent scenarios (VNAV Speed with the mode control panel (MCP) speed window open until flaps extended, then VNAV Path) in a commercial transport flight simulator with realistic visual scene and communications. The results of this study serve three practical aims: (1) contribute to the down-select of avionics configuration for future assessment of the ASTAR spacing algorithm at NASA; (2) provide information useful to the FAA Human Factors Division (ANG-C1)'s mission to identify issues pertinent to flight certification of, and flight standards; (3) identify methodological considerations in support of future FIM human-in-the-loop (HITL) investigations.
Energy and Cost Savings of Retro-Commissioning and Retrofit Measures for Large Office Buildings
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Weimin; Zhang, Jian; Moser, Dave
2012-08-03
This paper evaluates the energy and cost savings of seven retro-commissioning measures and 29 retrofit measures applicable to most large office buildings. The baseline model is for a hypothetical building with characteristics of large office buildings constructed before 1980. Each retro-commissioning measure is evaluated against the original baseline in terms of its potential of energy and cost savings while each retrofit measure is evaluated against the commissioned building. All measures are evaluated in five locations (Miami, Las Vegas, Seattle, Chicago and Duluth) to understand the impact of weather conditions on energy and cost savings. The results show that implementation ofmore » the seven operation and maintenance measures as part of a retro-commissioning process can yield an average of about 22% of energy use reduction and 14% of energy cost reduction. Widening zone temperature deadband, lowering VAV terminal minimum air flow set points and lighting upgrades are effective retrofit measures to be considered.« less
Park, So Jeong; Park, Doo Ri; Bhattarai, Deepak; Lee, Kyeong; Kim, Jaesang; Bae, Yun Soo; Lee, Soo Young
2014-08-01
2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity.
Valerio, Daria G; Xu, Haiming; Eisold, Meghan E; Woolthuis, Carolien M; Pandita, Tej K; Armstrong, Scott A
2017-01-05
K(lysine) acetyltransferase 8 (KAT8, also known as MOF) mediates the acetylation of histone H4 at lysine 16 (H4K16ac) and is crucial for murine embryogenesis. Lysine acetyltransferases have been shown to regulate various stages of normal hematopoiesis. However, the function of MOF in hematopoietic stem cell (HSC) development has not yet been elucidated. We set out to study the role of MOF in general hematopoiesis by using a Vav1-cre-induced conditional murine Mof knockout system and found that MOF is critical for hematopoietic cell maintenance and HSC engraftment capacity in adult hematopoiesis. Rescue experiments with a MOF histone acetyltransferase domain mutant illustrated the requirement for MOF acetyltransferase activity in the clonogenic capacity of HSCs and progenitors. In stark contrast, fetal steady-state hematopoiesis at embryonic day (E) 14.5 was not affected by homozygous Mof deletion despite dramatic loss of global H4K16ac. Hematopoietic defects start manifesting in late gestation at E17.5. The discovery that MOF and its H4K16ac activity are required for adult but not early and midgestational hematopoiesis supports the notion that multiple chromatin regulators may be crucial for hematopoiesis at varying stages of development. MOF is therefore a developmental-stage-specific chromatin regulator found to be essential for adult but not early fetal hematopoiesis. © 2017 by The American Society of Hematology.
Kiryluk, Krzysztof; Li, Yifu; Scolari, Francesco; Sanna-Cherchi, Simone; Choi, Murim; Verbitsky, Miguel; Fasel, David; Lata, Sneh; Prakash, Sindhuri; Shapiro, Samantha; Fischman, Clara; Snyder, Holly J.; Appel, Gerald; Izzi, Claudia; Viola, Battista Fabio; Dallera, Nadia; Vecchio, Lucia Del; Barlassina, Cristina; Salvi, Erika; Bertinetto, Francesca Eleonora; Amoroso, Antonio; Savoldi, Silvana; Rocchietti, Marcella; Amore, Alessandro; Peruzzi, Licia; Coppo, Rosanna; Salvadori, Maurizio; Ravani, Pietro; Magistroni, Riccardo; Ghiggeri, Gian Marco; Caridi, Gianluca; Bodria, Monica; Lugani, Francesca; Allegri, Landino; Delsante, Marco; Maiorana, Mariarosa; Magnano, Andrea; Frasca, Giovanni; Boer, Emanuela; Boscutti, Giuliano; Ponticelli, Claudio; Mignani, Renzo; Marcantoni, Carmelita; Di Landro, Domenico; Santoro, Domenico; Pani, Antonello; Polci, Rosaria; Feriozzi, Sandro; Chicca, Silvana; Galliani, Marco; Gigante, Maddalena; Gesualdo, Loreto; Zamboli, Pasquale; Maixnerová, Dita; Tesar, Vladimir; Eitner, Frank; Rauen, Thomas; Floege, Jürgen; Kovacs, Tibor; Nagy, Judit; Mucha, Krzysztof; Pączek, Leszek; Zaniew, Marcin; Mizerska-Wasiak, Małgorzata; Roszkowska-Blaim, Maria; Pawlaczyk, Krzysztof; Gale, Daniel; Barratt, Jonathan; Thibaudin, Lise; Berthoux, Francois; Canaud, Guillaume; Boland, Anne; Metzger, Marie; Panzer, Ulf; Suzuki, Hitoshi; Goto, Shin; Narita, Ichiei; Caliskan, Yasar; Xie, Jingyuan; Hou, Ping; Chen, Nan; Zhang, Hong; Wyatt, Robert J.; Novak, Jan; Julian, Bruce A.; Feehally, John; Stengel, Benedicte; Cusi, Daniele; Lifton, Richard P.; Gharavi, Ali G.
2014-01-01
We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six novel genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geo-spatial distribution of risk alleles is highly suggestive of multi-locus adaptation and the genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN. PMID:25305756
Fluorescein angiography and retinal vascular development in premature infants.
Purcaro, Velia; Velia, Purcaro; Baldascino, Antonio; Antonio, Baldascino; Papacci, Patrizia; Patrizia, Papacci; Giannantonio, Carmen; Carmen, Giannantonio; Molisso, Anna; Anna, Molisso; Molle, Fernando; Fernando, Molle; Lepore, Domenico; Domenico, Lepore; Romagnoli, Costantino; Costantino, Romagnoli
2012-10-01
To investigate the role of fluorescein angiography (FA) in the management of retinopathy of prematurity (ROP) in preterm newborns. An observational case series of 13 extremely low birth weight infants. From September 2009 to March 2010, 13 newborn infants with a gestational age <29 weeks end/or birth weight <1000 g underwent serial fluorescein angiography with RetCam (Clarity, Pleasanton, CA) every 2 weeks. The fluorescein angiograms were examined to optimize the timing of diagnosis of ROP and to investigate development of retinal and choroidal vascularization. There were no side effects related to FA. Variable features of retinal and choroidal circulation in preterm infants with a high risk of developing ROP were noted. FA allows vessels branching at the junction between vascular and avascular retina (V-Av junction) to be viewed easily and shows the ROP findings that sometimes cannot be seen by indirect ophthalmoscopy. Dye leakage is the most significant sign of progression to severe ROP or the need for surgery in newborn babies with ROP. RetCam-assisted intravenous FA is safe and allows a more objective assessment of the ROP stage and zone.
Identification of tick-borne encephalitis virus in ticks collected in southeastern Hungary.
Pintér, Réka; Madai, Mónika; Vadkerti, Edit; Németh, Viktória; Oldal, Miklós; Kemenesi, Gábor; Dallos, Bianka; Gyuranecz, Miklós; Kiss, Gábor; Bányai, Krisztián; Jakab, Ferenc
2013-09-01
Tick-borne encephalitis virus (TBEV) is an arthropod-borne viral pathogen causing infections in Europe and is responsible for most arbovirus central nervous system infections in Hungary. Assessing the TBEV prevalence in ticks through detection of genomic RNA is a broadly accepted approach to estimate the transmission risk from a tick bite. For this purpose, 2731 ticks were collected from the neighboring area of the town of Dévaványa, located in southeastern Hungary, which is considered a low-risk-transmission area for TBEV. Altogether, 2300 ticks were collected from the vegetation, while 431 were collected from rodents. Samples were pooled and then screened for TBEV with a newly designed semi-nested RT-PCR (RT-snPCR) targeting the NS1 genomic region. PCR results were confirmed by direct sequencing of the second round amplicons. Among the 3 different collected tick species (Ixodes ricinus, Haemaphysalis concinna, Dermacentor marginatus), I. ricinus was the only species that tested positive for TBEV. TBEV-positive ticks were collected from small mammals or from the vegetation. One nymphal pool and 4 larval pools tested positive for TBEV. The only positive nymphal pool was unfed and came from vegetation, while ticks of the 4 positive larval pools were collected from rodents. Minimal TBEV prevalence in ticks was 0.08% for unfed nymphs and 0.78% for feeding larvae. Our results indicate that further long-term investigations on the occurrence of TBEV are needed to better describe the geographic distribution and the prevalence of infected ticks in Hungary. Copyright © 2013 Elsevier GmbH. All rights reserved.
Boyle, Keith B; Gyori, David; Sindrilaru, Anca; Scharffetter-Kochanek, Karin; Taylor, Philip R; Mócsai, Attila; Stephens, Len R; Hawkins, Phillip T
2011-03-01
An effective immune response to the ubiquitous fungus Aspergillus fumigatus is dependent upon production of reactive oxygen species (ROS) by the NADPH oxidase. This is evidenced by the acute sensitivity of oxidase-deficient humans and mice to invasive aspergillosis. Neutrophils are recruited to the lungs shortly postinfection and respond by phagocytosing conidia and mediating extracellular killing of germinated hyphae in a ROS-dependent manner. However, the signaling mechanisms regulating the generation of ROS in response to hyphae are poorly understood. PI3Ks are important regulators of numerous cellular processes, with much recent work describing unique roles for the different class I PI3K isoforms. We showed by live-cell imaging that the lipid products of class I PI3Ks accumulated at the hyphal-bound neutrophil plasma membrane. Further, we used pharmacological and genetic approaches to demonstrate essential, but overlapping, roles for PI3Kβ and PI3Kδ in the ROS and spreading responses of murine neutrophils to Aspergillus hyphae. Hyphal-induced ROS responses were substantially inhibited by deletion of the common β2-integrin subunit CD18, with only a minor, redundant role for Dectin-1. However, addition of soluble algal glucans plus the genetic deletion of CD18 were required to significantly inhibit activation of the PI3K-effector protein kinase B. Hyphal ROS responses were also totally dependent on the presence of Syk, but not its ITAM-containing adaptor proteins FcRγ or DAP12, and the Vav family of Rac-guanine nucleotide exchange factors. These results start to define the signaling network controlling neutrophil ROS responses to A. fumigatus hyphae.
Zhong, Ming-Chao; Veillette, André
2013-01-01
Signaling lymphocytic activation molecule-associated protein (SAP) is an Src homology 2 domain-only adaptor involved in multiple immune cell functions. It has also been linked to immunodeficiencies and autoimmune diseases, such as systemic lupus erythematosus. Here, we examined the role and mechanism of action of SAP in autoimmunity using a mouse model of autoimmune arthritis, collagen-induced arthritis (CIA). We found that SAP was essential for development of CIA in response to collagen immunization. It was also required for production of collagen-specific antibodies, which play a key role in disease pathogenesis. These effects required SAP expression in T cells, not in B cells. In mice immunized with a high dose of collagen, the activity of SAP was nearly independent of its ability to bind the protein tyrosine kinase Fyn and correlated with the capacity of SAP to promote full differentiation of follicular T helper (TFH) cells. However, with a lower dose of collagen, the role of SAP was more dependent on Fyn binding, suggesting that additional mechanisms other than TFH cell differentiation were involved. Further studies suggested that this might be due to a role of the SAP-Fyn interaction in natural killer T cell development through the ability of SAP-Fyn to promote Vav-1 activation. We also found that removal of SAP expression during progression of CIA attenuated disease severity. However, it had no effect on disease when CIA was clinically established. Together, these results indicate that SAP plays an essential role in CIA because of Fyn-independent and Fyn-dependent effects on TFH cells and, possibly, other T cell types. PMID:24045941
Zhong, Ming-Chao; Veillette, André
2013-11-01
Signaling lymphocytic activation molecule-associated protein (SAP) is an Src homology 2 domain-only adaptor involved in multiple immune cell functions. It has also been linked to immunodeficiencies and autoimmune diseases, such as systemic lupus erythematosus. Here, we examined the role and mechanism of action of SAP in autoimmunity using a mouse model of autoimmune arthritis, collagen-induced arthritis (CIA). We found that SAP was essential for development of CIA in response to collagen immunization. It was also required for production of collagen-specific antibodies, which play a key role in disease pathogenesis. These effects required SAP expression in T cells, not in B cells. In mice immunized with a high dose of collagen, the activity of SAP was nearly independent of its ability to bind the protein tyrosine kinase Fyn and correlated with the capacity of SAP to promote full differentiation of follicular T helper (TFH) cells. However, with a lower dose of collagen, the role of SAP was more dependent on Fyn binding, suggesting that additional mechanisms other than TFH cell differentiation were involved. Further studies suggested that this might be due to a role of the SAP-Fyn interaction in natural killer T cell development through the ability of SAP-Fyn to promote Vav-1 activation. We also found that removal of SAP expression during progression of CIA attenuated disease severity. However, it had no effect on disease when CIA was clinically established. Together, these results indicate that SAP plays an essential role in CIA because of Fyn-independent and Fyn-dependent effects on TFH cells and, possibly, other T cell types.
PH motifs in PAR1&2 endow breast cancer growth.
Kancharla, A; Maoz, M; Jaber, M; Agranovich, D; Peretz, T; Grisaru-Granovsky, S; Uziely, B; Bar-Shavit, R
2015-11-24
Although emerging roles of protease-activated receptor1&2 (PAR1&2) in cancer are recognized, their underlying signalling events are poorly understood. Here we show signal-binding motifs in PAR1&2 that are critical for breast cancer growth. This occurs via the association of the pleckstrin homology (PH) domain with Akt/PKB as a key signalling event of PARs. Other PH-domain signal-proteins such as Etk/Bmx and Vav3 also associate with PAR1 and PAR2 through their PH domains. PAR1 and PAR2 bind with priority to Etk/Bmx. A point mutation in PAR2, H349A, but not in R352A, abrogates PH-protein association and is sufficient to markedly reduce PAR2-instigated breast tumour growth in vivo and placental extravillous trophoblast (EVT) invasion in vitro. Similarly, the PAR1 mutant hPar1-7A, which is unable to bind the PH domain, reduces mammary tumours and EVT invasion, endowing these motifs with physiological significance and underscoring the importance of these previously unknown PAR1 and PAR2 PH-domain-binding motifs in both pathological and physiological invasion processes.
Functional hierarchy of the N-terminal tyrosines of SLP-76.
Jordan, Martha S; Sadler, Jeffrey; Austin, Jessica E; Finkelstein, Lisa D; Singer, Andrew L; Schwartzberg, Pamela L; Koretzky, Gary A
2006-02-15
The adaptor protein Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) plays a central role in T cell activation and T cell development. SLP-76 has three functional modules: an acidic domain with three key tyrosines, a central proline-rich domain, and a C-terminal Src homology 2 domain. Of these, mutation of the three N-terminal tyrosines (Y112, Y128, and Y145) results in the most profound effects on T cell development and function. Y112 and Y128 associate with Vav and Nck, two proteins shown to be important for TCR-induced phosphorylation of proximal signaling substrates, Ca(2+) flux, and actin reorganization. Y145 has been shown to be important for optimal association of SLP-76 with inducible tyrosine kinase, a key regulator of T cell function. To investigate further the role of the phosphorylatable tyrosines of SLP-76 in TCR signaling, cell lines and primary T cells expressing SLP-76 with mutations in individual or paired tyrosine residues were analyzed. These studies show that Tyr(145) of SLP-76 is the most critical tyrosine for both T cell function in vitro and T cell development in vivo.
Moreno, M A; Domínguez, L; Teshager, T; Herrero, I A; Porrero, M C
2000-05-01
Antimicrobial resistance is a problem in modern public health and antimicrobial use and especially misuse, the most important selecting force for bacterial antibiotic resistance. As this resistance must be monitored we have designed the Spanish network 'Red de Vigilancia de Resistencias Antibióticas en Bacterias de Origen Veterinario'. This network covers the three critical points of veterinary responsibility, bacteria from sick animals, bacteria from healthy animals and bacteria from food animals. Key bacteria, antimicrobials and animal species have been defined for each of these groups along with laboratory methods for testing antimicrobial susceptibility and for data analysis and reporting. Surveillance of sick animals was first implemented using Escherichia coli as the sentinel bacterium. Surveillance of E. coli and Enterococcus faecium from healthy pigs was implemented in 1998. In July 1999, data collection on Salmonella spp. was initiated in poultry slaughterhouses. Additionally, the prevalence of vancomycin resistant E. faecium was also monitored. This network has specific topics of interest related to methods of determining resistance, analysis and reporting of data, methods of use for veterinary practitioners and collaboration with public health authorities.
Verifying the body tide at the Canary Islands using tidal gravimetry observations
NASA Astrophysics Data System (ADS)
Arnoso, J.; Benavent, M.; Bos, M. S.; Montesinos, F. G.; Vieira, R.
2011-05-01
Gravity tide records from El Hierro, Tenerife and Lanzarote Islands (Canarian Archipelago) have been analyzed and compared to the theoretical body tide model (DDW) of Dehant el al. (1999). The use of more stringent criterion of tidal analysis using VAV program allowed us to reduce the error bars by a factor of two of the gravimetric factors at Tenerife and Lanzarote compared with previous published values. Also, the calibration values have been revisited at those sites. Precise ocean tide loading (OTL) corrections based on up-to-date global ocean models and improved regional ocean model have been obtained for the main tidal harmonics O 1, K 1, M 2, S 2. We also point out the importance of using the most accurate coastline definition for OTL calculations in the Canaries. The remaining observational errors depend on the accuracy of the calibration of the gravimeters and/or on the length of the observed data series. Finally, the comparison of the tidal observations with the theoretical body tide models has been done with an accuracy level of 0.1% at El Hierro, 0.4% at Tenerife and 0.5% at Lanzarote.
Economic, Environmental and Health Implications of Enhanced Ventilation in Office Buildings.
MacNaughton, Piers; Pegues, James; Satish, Usha; Santanam, Suresh; Spengler, John; Allen, Joseph
2015-11-18
Current building ventilation standards are based on acceptable minimums. Three decades of research demonstrates the human health benefits of increased ventilation above these minimums. Recent research also shows the benefits on human decision-making performance in office workers, which translates to increased productivity. However, adoption of enhanced ventilation strategies is lagging. We sought to evaluate two of the perceived potential barriers to more widespread adoption-Economic and environmental costs. We estimated the energy consumption and associated per building occupant costs for office buildings in seven U.S. cities, representing different climate zones for three ventilation scenarios (standard practice (20 cfm/person), 30% enhanced ventilation, and 40 cfm/person) and four different heating, ventilation and air conditioning (HVAC) system strategies (Variable Air Volume (VAV) with reheat and a Fan Coil Unit (FCU), both with and without an energy recovery ventilator). We also estimated emissions of greenhouse gases associated with this increased energy usage, and, for comparison, converted this to the equivalent number of vehicles using greenhouse gas equivalencies. Lastly, we paired results from our previous research on cognitive function and ventilation with labor statistics to estimate the economic benefit of increased productivity associated with increasing ventilation rates. Doubling the ventilation rate from the American Society of Heating, Refrigeration and Air-Conditioning Engineers minimum cost less than $40 per person per year in all climate zones investigated. Using an energy recovery ventilation system significantly reduced energy costs, and in some scenarios led to a net savings. At the highest ventilation rate, adding an ERV essentially neutralized the environmental impact of enhanced ventilation (0.03 additional cars on the road per building across all cities). The same change in ventilation improved the performance of workers by 8%, equivalent to a $6500 increase in employee productivity each year. Reduced absenteeism and improved health are also seen with enhanced ventilation. The health benefits associated with enhanced ventilation rates far exceed the per-person energy costs relative to salary costs. Environmental impacts can be mitigated at regional, building, and individual-level scales through the transition to renewable energy sources, adoption of energy efficient systems and ventilation strategies, and promotion of other sustainable policies.
Economic, Environmental and Health Implications of Enhanced Ventilation in Office Buildings
MacNaughton, Piers; Pegues, James; Satish, Usha; Santanam, Suresh; Spengler, John; Allen, Joseph
2015-01-01
Introduction: Current building ventilation standards are based on acceptable minimums. Three decades of research demonstrates the human health benefits of increased ventilation above these minimums. Recent research also shows the benefits on human decision-making performance in office workers, which translates to increased productivity. However, adoption of enhanced ventilation strategies is lagging. We sought to evaluate two of the perceived potential barriers to more widespread adoption—Economic and environmental costs. Methods: We estimated the energy consumption and associated per building occupant costs for office buildings in seven U.S. cities, representing different climate zones for three ventilation scenarios (standard practice (20 cfm/person), 30% enhanced ventilation, and 40 cfm/person) and four different heating, ventilation and air conditioning (HVAC) system strategies (Variable Air Volume (VAV) with reheat and a Fan Coil Unit (FCU), both with and without an energy recovery ventilator). We also estimated emissions of greenhouse gases associated with this increased energy usage, and, for comparison, converted this to the equivalent number of vehicles using greenhouse gas equivalencies. Lastly, we paired results from our previous research on cognitive function and ventilation with labor statistics to estimate the economic benefit of increased productivity associated with increasing ventilation rates. Results: Doubling the ventilation rate from the American Society of Heating, Refrigeration and Air-Conditioning Engineers minimum cost less than $40 per person per year in all climate zones investigated. Using an energy recovery ventilation system significantly reduced energy costs, and in some scenarios led to a net savings. At the highest ventilation rate, adding an ERV essentially neutralized the environmental impact of enhanced ventilation (0.03 additional cars on the road per building across all cities). The same change in ventilation improved the performance of workers by 8%, equivalent to a $6500 increase in employee productivity each year. Reduced absenteeism and improved health are also seen with enhanced ventilation. Conclusions: The health benefits associated with enhanced ventilation rates far exceed the per-person energy costs relative to salary costs. Environmental impacts can be mitigated at regional, building, and individual-level scales through the transition to renewable energy sources, adoption of energy efficient systems and ventilation strategies, and promotion of other sustainable policies. PMID:26593933
Chiva-Blanch, Gemma; Crespo, Javier; Suades, Rosa; Arderiu, Gemma; Padro, Teresa; Vilahur, Gemma; Cubedo, Judith; Corella, Dolores; Salas-Salvadó, Jordi; Arós, Fernando; Martínez-González, Miguel-Angel; Ros, Emilio; Fitó, Montse; Estruch, Ramon; Badimon, Lina
2016-07-04
Circulating microparticles (cMPs) are small phospholipid-rich microvesicles shed by activated cells that play a pivotal role in cell signalling related to the pathogenesis of atherothrombosis. We aimed to investigate the prognostic value of cMPs released from different vascular cells for cardiovascular event (CVE) presentation in asymptomatic patients at high cardiovascular risk factors under nutritional and pharmacologic treatment. This is a nested case-control study of 50 patients from the five-year follow-up prospective PREDIMED trial enrolled in the nuts arm of the Mediterranean diet (MedDiet-nuts). We randomly selected 25 patients who had suffered a CVE during follow-up and pair-matched them for sex, age, and classical CV risk factors to 25 patients who remained asymptomatic (no-CVE). Total Annexin V-(AV)+ cMPs and cMPs from cells of the vascular compartment were quantified by flow cytometry at baseline and after one year follow-up. MedDiet-nuts and pharmacological treatment neither modified levels nor source of MP shedding in CVE patients. However, no-CVE patients showed 40-86 % decreased total AV+, PAC-1+/AV+, CD61+/AV+, CD142+/CD61+/AV+, CD62P+/AV+, CD146+/AV+, CD63+/AV+ and CD11a+/AV+ cMPs at one year follow-up (p≤0.046, all). CD142+/CD61+/AV+, CD146+/AV+ and CD45+/AV+ cMPs were decreased in no-CVE patients compared to CVE patients. A ROC-curve clustered model for CD142+/CD61+/AV+, CD45+/AV+ and CD146+/AV+ cMPs predicted a future CVE [p<0.0001, AUC=0.805 (0.672 to 0.938)]. In patients at high CV risk profile treated with a controlled MedDiet supplemented with nuts and receiving up-to-date CV drug treatment, reduced cMPs derived from activated platelets, leukocytes and endothelial cells are predictive of protection against CVE within the next four years.
Kon, Ayana; Yamazaki, Satoshi; Nannya, Yasuhito; Kataoka, Keisuke; Ota, Yasunori; Nakagawa, Masahiro Marshall; Yoshida, Kenichi; Shiozawa, Yusuke; Morita, Maiko; Yoshizato, Tetsuichi; Sanada, Masashi; Nakayama, Manabu; Koseki, Haruhiko; Nakauchi, Hiromitsu; Ogawa, Seishi
2018-02-08
Splicing factor mutations are characteristic of myelodysplastic syndromes (MDS) and related myeloid neoplasms and implicated in their pathogenesis, but their roles in the development of MDS have not been fully elucidated. In the present study, we investigated the consequence of mutant Srsf2 expression using newly generated Vav1-Cre -mediated conditional knockin mice. Mice carrying a heterozygous Srsf2 P95H mutation showed significantly reduced numbers of hematopoietic stem and progenitor cells (HSPCs) and differentiation defects both in the steady-state condition and transplantation settings. Srsf2 -mutated hematopoietic stem cells (HSCs) showed impaired long-term reconstitution compared with control mice in competitive repopulation assays. Although the Srsf2 mutant mice did not develop MDS under the steady-state condition, when their stem cells were transplanted into lethally irradiated mice, the recipients developed anemia, leukopenia, and erythroid dysplasia, which suggests the role of replicative stress in the development of an MDS-like phenotype in Srsf2 -mutated mice. RNA sequencing of the Srsf2 -mutated HSPCs revealed a number of abnormal splicing events and differentially expressed genes, including several potential targets implicated in the pathogenesis of hematopoietic malignancies, such as Csf3r , Fyn , Gnas , Nsd1 , Hnrnpa2b1 , and Trp53bp1 Among the mutant Srsf2 -associated splicing events, most commonly observed were the enhanced inclusion and/or exclusion of cassette exons, which were caused by the altered consensus motifs for the recognition of exonic splicing enhancers. Our findings suggest that the mutant Srsf2 leads to a compromised HSC function by causing abnormal RNA splicing and expression, contributing to the deregulated hematopoiesis that recapitulates the MDS phenotypes, possibly as a result of additional genetic and/or environmental insults. © 2018 by The American Society of Hematology.
Kokavec, Juraj; Zikmund, Tomas; Savvulidi, Filipp; Kulvait, Vojtech; Edelmann, Winfried; Skoultchi, Arthur I; Stopka, Tomas
2017-06-01
The imitation switch nuclear ATPase Smarca5 (Snf2h) is one of the most conserved chromatin remodeling factors. It exists in a variety of oligosubunit complexes that move DNA with respect to the histone octamer to generate regularly spaced nucleosomal arrays. Smarca5 interacts with different accessory proteins and represents a molecular motor for DNA replication, repair, and transcription. We deleted Smarca5 at the onset of definitive hematopoiesis (Vav1-iCre) and observed that animals die during late fetal development due to anemia. Hematopoietic stem and progenitor cells accumulated but their maturation toward erythroid and myeloid lineages was inhibited. Proerythroblasts were dysplastic while basophilic erythroblasts were blocked in G2/M and depleted. Smarca5 deficiency led to increased p53 levels, its activation at two residues, one associated with DNA damage (S15 Ph ° s ) second with CBP/p300 (K376 Ac ), and finally activation of the p53 targets. We also deleted Smarca5 in committed erythroid cells (Epor-iCre) and observed that animals were anemic postnatally. Furthermore, 4-hydroxytamoxifen-mediated deletion of Smarca5 in the ex vivo cultures confirmed its requirement for erythroid cell proliferation. Thus, Smarca5 plays indispensable roles during early hematopoiesis and erythropoiesis. Stem Cells 2017;35:1614-1623. © 2017 AlphaMed Press.
Rodriguez, Ramon M; Suarez-Alvarez, Beatriz; Lavín, José L; Mosén-Ansorena, David; Baragaño Raneros, Aroa; Márquez-Kisinousky, Leonardo; Aransay, Ana M; Lopez-Larrea, Carlos
2017-01-15
Epigenetic mechanisms play a critical role during differentiation of T cells by contributing to the formation of stable and heritable transcriptional patterns. To better understand the mechanisms of memory maintenance in CD8 + T cells, we performed genome-wide analysis of DNA methylation, histone marking (acetylated lysine 9 in histone H3 and trimethylated lysine 9 in histone), and gene-expression profiles in naive, effector memory (EM), and terminally differentiated EM (TEMRA) cells. Our results indicate that DNA demethylation and histone acetylation are coordinated to generate the transcriptional program associated with memory cells. Conversely, EM and TEMRA cells share a very similar epigenetic landscape. Nonetheless, the TEMRA transcriptional program predicts an innate immunity phenotype associated with genes never reported in these cells, including several mediators of NK cell activation (VAV3 and LYN) and a large array of NK receptors (e.g., KIR2DL3, KIR2DL4, KIR2DL1, KIR3DL1, KIR2DS5). In addition, we identified up to 161 genes that encode transcriptional regulators, some of unknown function in CD8 + T cells, and that were differentially expressed in the course of differentiation. Overall, these results provide new insights into the regulatory networks involved in memory CD8 + T cell maintenance and T cell terminal differentiation. Copyright © 2017 by The American Association of Immunologists, Inc.
Chen, Yu-Li; Hwang, Tsong-Long; Yu, Huang-Ping; Fang, Jia-You; Chong, Kowit Yu; Chang, Yao-Wen; Chen, Chun-Yu; Yang, Hsuan-Wu; Chang, Wen-Yi; Hsieh, Pei-Wen
2016-01-01
Acute lung injury (ALI) is a severe respiratory disease with high mortality rates worldwide. Recent reports suggest that human neutrophil elastase (HNE) plays a key role in the inflammatory response that is characteristic of ALI, which indicates that the development of HNE inhibitors could be an efficient treatment strategy. In the current study, an enzyme-based screening assay was used to identify effective HNE inhibitors from a number of traditional Chinese medicines (TCMs). Among them, a water extract of Ilex kaushue (IKWE) effectively inhibited HNE activity (IC50, 11.37 ± 1.59 μg/mL). Using bioactivity-guided fractionation, one new compound and 23 known compounds were identified. Compound 6 (identified as 3,5-dicaffeoylquinic acid; 3,5-DCQA) exerted the most potent and selective inhibitory effect on HNE activity (IC50, 1.86 ± 0.06 μM). In a cell-based assay, 3,5-DCQA not only directly reduced superoxide generation and elastase activity but also attenuated the Src family kinase (SRKs)/Vav signaling pathway in N-formyl-L-Met-L-Leu-L-Phe (fMLF)-stimulated human neutrophils. In an animal disease model, both 3,5-DCQA and standardized IKWE protected against lipopolysaccharide-induced ALI in mice, which provides support for their potential as candidates in the development of new therapeutic agents for neutrophilic inflammatory diseases. PMID:27681838
IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics.
Sasaki, Masato; Knobbe, Christiane B; Munger, Joshua C; Lind, Evan F; Brenner, Dirk; Brüstle, Anne; Harris, Isaac S; Holmes, Roxanne; Wakeham, Andrew; Haight, Jillian; You-Ten, Annick; Li, Wanda Y; Schalm, Stefanie; Su, Shinsan M; Virtanen, Carl; Reifenberger, Guido; Ohashi, Pamela S; Barber, Dwayne L; Figueroa, Maria E; Melnick, Ari; Zúñiga-Pflücker, Juan-Carlos; Mak, Tak W
2012-08-30
Mutations in the IDH1 and IDH2 genes encoding isocitrate dehydrogenases are frequently found in human glioblastomas and cytogenetically normal acute myeloid leukaemias (AML). These alterations are gain-of-function mutations in that they drive the synthesis of the ‘oncometabolite’ R-2-hydroxyglutarate (2HG). It remains unclear how IDH1 and IDH2 mutations modify myeloid cell development and promote leukaemogenesis. Here we report the characterization of conditional knock-in (KI) mice in which the most common IDH1 mutation, IDH1(R132H), is inserted into the endogenous murine Idh1 locus and is expressed in all haematopoietic cells (Vav-KI mice) or specifically in cells of the myeloid lineage (LysM-KI mice). These mutants show increased numbers of early haematopoietic progenitors and develop splenomegaly and anaemia with extramedullary haematopoiesis, suggesting a dysfunctional bone marrow niche. Furthermore, LysM-KI cells have hypermethylated histones and changes to DNA methylation similar to those observed in human IDH1- or IDH2-mutant AML. To our knowledge, our study is the first to describe the generation and characterization of conditional IDH1(R132H)-KI mice, and also the first report to demonstrate the induction of a leukaemic DNA methylation signature in a mouse model. Our report thus sheds light on the mechanistic links between IDH1 mutation and human AML.
Belmont, Judson; Gu, Tao; Mudd, Ashley; Salomon, Arthur R
2017-08-04
Phospholipase C gamma 1 (PLC-γ1) occupies a critically important position in the T-cell signaling pathway. While its functions as a regulator of both Ca 2+ signaling and PKC-family kinases are well characterized, PLC-γ1's role in the regulation of early T-cell receptor signaling events is incompletely understood. Activation of the T-cell receptor leads to the formation of a signalosome complex between SLP-76, LAT, PLC-γ1, Itk, and Vav1. Recent studies have revealed the existence of both positive and negative feedback pathways from SLP-76 to the apical kinase in the pathway, Lck. To determine if PLC-γ1 contributes to the regulation of these feedback networks, we performed a quantitative phosphoproteomic analysis of PLC-γ1-deficient T cells. These data revealed a previously unappreciated role for PLC-γ1 in the positive regulation of Zap-70 and T-cell receptor tyrosine phosphorylation. Conversely, PLC-γ1 negatively regulated the phosphorylation of SLP-76-associated proteins, including previously established Lck substrate phosphorylation sites within this complex. While the positive and negative regulatory phosphorylation sites on Lck were largely unchanged, Tyr 192 phosphorylation was elevated in Jgamma1. The data supports a model wherein Lck's targeting, but not its kinase activity, is altered by PLC-γ1, possibly through Lck Tyr 192 phosphorylation and increased association of the kinase with protein scaffolds SLP-76 and TSAd.
Sarmady, Mahdi; Dampier, William; Tozeren, Aydin
2011-01-01
Virus proteins alter protein pathways of the host toward the synthesis of viral particles by breaking and making edges via binding to host proteins. In this study, we developed a computational approach to predict viral sequence hotspots for binding to host proteins based on sequences of viral and host proteins and literature-curated virus-host protein interactome data. We use a motif discovery algorithm repeatedly on collections of sequences of viral proteins and immediate binding partners of their host targets and choose only those motifs that are conserved on viral sequences and highly statistically enriched among binding partners of virus protein targeted host proteins. Our results match experimental data on binding sites of Nef to host proteins such as MAPK1, VAV1, LCK, HCK, HLA-A, CD4, FYN, and GNB2L1 with high statistical significance but is a poor predictor of Nef binding sites on highly flexible, hoop-like regions. Predicted hotspots recapture CD8 cell epitopes of HIV Nef highlighting their importance in modulating virus-host interactions. Host proteins potentially targeted or outcompeted by Nef appear crowding the T cell receptor, natural killer cell mediated cytotoxicity, and neurotrophin signaling pathways. Scanning of HIV Nef motifs on multiple alignments of hepatitis C protein NS5A produces results consistent with literature, indicating the potential value of the hotspot discovery in advancing our understanding of virus-host crosstalk. PMID:21738584
Caudell, David; Harper, David P; Novak, Rachel L; Pierce, Rachel M; Slape, Christopher; Wolff, Linda; Aplan, Peter D
2010-02-11
The t(10;11) translocation results in a CALM-AF10 fusion gene in a subset of leukemia patients. Expression of a CALM-AF10 transgene results in leukemia, with prolonged latency and incomplete penetrance, suggesting that additional events are necessary for leukemic transformation. CALM-AF10 mice infected with the MOL4070LTR retrovirus developed acute leukemia, and ligation-mediated polymerase chain reaction was used to identify retroviral insertions at 19 common insertion sites, including Zeb2, Nf1, Mn1, Evi1, Ift57, Mpl, Plag1, Kras, Erg, Vav1, and Gata1. A total of 26% (11 of 42) of the mice had retroviral integrations near Zeb2, a transcriptional corepressor leading to overexpression of the Zeb2-transcript. A total of 91% (10 of 11) of mice with Zeb2 insertions developed B-lineage acute lymphoblastic leukemia, suggesting that Zeb2 activation promotes the transformation of CALM-AF10 hematopoietic precursors toward B-lineage leukemias. More than half of the mice with Zeb2 integrations also had Nf1 integrations, suggesting cooperativity among CALM-AF10, Zeb2, and Ras pathway mutations. We searched for Nras, Kras, and Ptpn11 point mutations in the CALM-AF10 leukemic mice. Three mutations were identified, all of which occurred in mice with Zeb2 integrations, consistent with the hypothesis that Zeb2 and Ras pathway activation promotes B-lineage leukemic transformation in concert with CALM-AF10.
Caudell, David; Harper, David P.; Novak, Rachel L.; Pierce, Rachel M.; Slape, Christopher; Wolff, Linda
2010-01-01
The t(10;11) translocation results in a CALM-AF10 fusion gene in a subset of leukemia patients. Expression of a CALM-AF10 transgene results in leukemia, with prolonged latency and incomplete penetrance, suggesting that additional events are necessary for leukemic transformation. CALM-AF10 mice infected with the MOL4070LTR retrovirus developed acute leukemia, and ligation-mediated polymerase chain reaction was used to identify retroviral insertions at 19 common insertion sites, including Zeb2, Nf1, Mn1, Evi1, Ift57, Mpl, Plag1, Kras, Erg, Vav1, and Gata1. A total of 26% (11 of 42) of the mice had retroviral integrations near Zeb2, a transcriptional corepressor leading to overexpression of the Zeb2-transcript. A total of 91% (10 of 11) of mice with Zeb2 insertions developed B-lineage acute lymphoblastic leukemia, suggesting that Zeb2 activation promotes the transformation of CALM-AF10 hematopoietic precursors toward B-lineage leukemias. More than half of the mice with Zeb2 integrations also had Nf1 integrations, suggesting cooperativity among CALM-AF10, Zeb2, and Ras pathway mutations. We searched for Nras, Kras, and Ptpn11 point mutations in the CALM-AF10 leukemic mice. Three mutations were identified, all of which occurred in mice with Zeb2 integrations, consistent with the hypothesis that Zeb2 and Ras pathway activation promotes B-lineage leukemic transformation in concert with CALM-AF10. PMID:20007546
A prognostic mutation panel for predicting cancer recurrence in stages II and III colorectal cancer.
Sho, Shonan; Court, Colin M; Winograd, Paul; Russell, Marcia M; Tomlinson, James S
2017-12-01
Approximately 20-40% of stage II/III colorectal cancer (CRC) patients develop relapse. Clinicopathological factors alone are limited in detecting these patients, resulting in potential under/over-treatment. We sought to identify a prognostic tumor mutational profile that could predict CRC recurrence. Whole-exome sequencing data were obtained for 207 patients with stage II/III CRC from The Cancer Genome Atlas. Mutational landscape in relapse-free versus relapsed cohort was compared using Fisher's exact test, followed by multivariate Cox regression to identify genes associated with cancer recurrence. Bootstrap-validation was used to examine internal/external validity. We identified five prognostic genes (APAF1, DIAPH2, NTNG1, USP7, and VAV2), which were combined to form a prognostic mutation panel. Patients with ≥1 mutation(s) within this five-gene panel had worse prognosis (3-yr relapse-free survival [RFS]: 53.0%), compared to patients with no mutation (3-yr RFS: 84.3%). In multivariate analysis, the five-gene panel remained prognostic for cancer recurrence independent of stage and high-risk features (hazard ratio 3.63, 95%CI [1.93-6.83], P < 0.0001). Furthermore, its prognostic accuracy was superior to the American Joint Commission on Cancer classification (concordance-index: 0.70 vs 0.54). Our proposed mutation panel identifies CRC patients at high-risk for recurrence, which may help guide adjuvant therapy and post-operative surveillance protocols. © 2017 Wiley Periodicals, Inc.
Bard-Chapeau, Emilie A.; Szumska, Dorota; Jacob, Bindya; Chua, Belinda Q. L.; Chatterjee, Gouri C.; Zhang, Yi; Ward, Jerrold M.; Urun, Fatma; Kinameri, Emi; Vincent, Stéphane D.; Ahmed, Sayadi; Bhattacharya, Shoumo; Osato, Motomi; Perkins, Archibald S.; Moore, Adrian W.; Jenkins, Nancy A.; Copeland, Neal G.
2014-01-01
The ecotropic viral integration site 1 (Evi1) oncogenic transcription factor is one of a number of alternative transcripts encoded by the Mds1 and Evi1 complex locus (Mecom). Overexpression of Evi1 has been observed in a number of myeloid disorders and is associated with poor patient survival. It is also amplified and/or overexpressed in many epithelial cancers including nasopharyngeal carcinoma, ovarian carcinoma, ependymomas, and lung and colorectal cancers. Two murine knockout models have also demonstrated Evi1's critical role in the maintenance of hematopoietic stem cell renewal with its absence resulting in the death of mutant embryos due to hematopoietic failure. Here we characterize a novel mouse model (designated Evi1fl3) in which Evi1 exon 3, which carries the ATG start, is flanked by loxP sites. Unexpectedly, we found that germline deletion of exon3 produces a hypomorphic allele due to the use of an alternative ATG start site located in exon 4, resulting in a minor Evi1 N-terminal truncation and a block in expression of the Mds1-Evi1 fusion transcript. Evi1δex3/δex3 mutant embryos showed only a mild non-lethal hematopoietic phenotype and bone marrow failure was only observed in adult Vav-iCre/+, Evi1fl3/fl3 mice in which exon 3 was specifically deleted in the hematopoietic system. Evi1δex3/δex3 knockout pups are born in normal numbers but die during the perinatal period from congenital heart defects. Database searches identified 143 genes with similar mutant heart phenotypes as those observed in Evi1δex3/δex3 mutant pups. Interestingly, 42 of these congenital heart defect genes contain known Evi1-binding sites, and expression of 18 of these genes are also effected by Evi1 siRNA knockdown. These results show a potential functional involvement of Evi1 target genes in heart development and indicate that Evi1 is part of a transcriptional program that regulates cardiac development in addition to the development of blood. PMID:24586749
Ogi, Kazuhiro; Nakashima, Kenji; Chihara, Kazuyasu; Takeuchi, Kenji; Horiguchi, Tomoko; Fujieda, Shigeharu; Sada, Kiyonao
2011-09-01
Tyrosine phosphorylation of adaptor protein c-Abl-Src homology 3 (SH3) domain-binding protein-2 (3BP2, also referred to SH3BP2) positively regulates the B-cell antigen receptor (BCR)-mediated signal transduction, leading to the activation of nuclear factor of activated T cells (NFAT). Here we showed the effect of the proline to arginine substitution of 3BP2 in which is the most common mutation in patients with cherubism (P418R) on B-cell receptor signaling. Comparing to the wild type, overexpression of the mutant form of 3BP2 (3BP2-P416R, corresponding to P418R in human protein) enhanced BCR-mediated activation of NFAT. 3BP2-P416R increased the signaling complex formation with Syk, phospholipase C-γ2 (PLC-γ2), and Vav1. In contrast, 3BP2-P416R could not change the association with the negative regulator 14-3-3. Loss of the association mutant that was incapable to associate with 14-3-3 could not mimic BCR-mediated NFAT activation in Syk-deficient cells. Moreover, BCR-mediated phosphorylation of extracellular signal regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) was not affected by P416R mutation. These results showed that P416R mutation of 3BP2 causes the gain of function in B cells by increasing the interaction with specific signaling molecules. © 2011 The Authors. Journal compilation © 2011 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.
Chauveau, Anne; Aucher, Anne; Eissmann, Philipp; Vivier, Eric; Davis, Daniel M.
2010-01-01
Membrane nanotubes are membranous tethers that physically link cell bodies over long distances. Here, we present evidence that nanotubes allow human natural killer (NK) cells to interact functionally with target cells over long distances. Nanotubes were formed when NK cells contacted target cells and moved apart. The frequency of nanotube formation was dependent on the number of receptor/ligand interactions and increased on NK cell activation. Most importantly, NK cell nanotubes contained a submicron scale junction where proteins accumulated, including DAP10, the signaling adaptor that associates with the activating receptor NKG2D, and MHC class I chain-related protein A (MICA), a cognate ligand for NKG2D, as occurs at close intercellular synapses between NK cells and target cells. Quantitative live-cell fluorescence imaging suggested that MICA accumulated at small nanotube synapses in sufficient numbers to trigger cell activation. In addition, tyrosine-phosphorylated proteins and Vav-1 accumulated at such junctions. Functionally, nanotubes could aid the lysis of distant target cells either directly or by moving target cells along the nanotube path into close contact for lysis via a conventional immune synapse. Target cells moving along the nanotube path were commonly polarized such that their uropods faced the direction of movement. This is the opposite polarization than for normal cell migration, implying that nanotubes can specifically drive target cell movement. Finally, target cells that remained connected to an NK cell by a nanotube were frequently lysed, whereas removing the nanotube using a micromanipulator reduced lysis of these target cells. PMID:20212116
Rare case of diffuse spinal arachnoiditis following a complicated vertebral artery dissection.
Atallah, Elias; Dang, Sophia; Rahm, Sage; Feghali, James; Nohra, Chalouhi; Tjoumakaris, Stavropoula; Rosenwasser, Robert H; Zarzour, Hekmat; Herial, Nabeel; Gooch, Michael Reid; Jabbour, Pascal
2018-06-01
Spinal arachnoiditis (SA) is an extremely rare and delayed complication of subarachnoid hemorrhage (SAH). Little is known about its underlying pathogenesis and subsequent clinical course. A middle-aged patient presented with the worst headache of her life and a grade 3 SAH of the basal-cisterns and posterior fossa was identified on Computed Tomography scans (CT). Angiography revealed a ruptured dissecting aneurysm of the left vertebral artery (VA-V4), as well as an unruptured left Anterior Cerebral Artery (ACA-A1) aneurysm. The VA aneurysm was treated with flow diversion. The patient re-ruptured the stented aneurysm, another telescoping pipeline was placed. The patient developed polymicrobial ventriculitis, and returned several months later complaining of paraparesis and left sided weakness. Magnetic Resonance Imaging (MRI) revealed diffuse thecal dural thickening from the cervicomedullary junction to the sacrum. Loculations, diffuse edema and cord compression were noticed along the inferior surface of the cerebellum, and the cervico-thoracic spine with a T4-T6 syrinx. The patient underwent a posterior (T4-T8) spinal fusion and (T5-T7) decompression with arachnoid-cyst fenestration and placement of a subarachnoid-pleural shunt. On latest follow-up, the patient is weaning off the thoraco-lumbosacral orthosis and ambulating with a cane. SA is often a complicated two-staged disease in which a "free interval phase" separates the initial inflammatory reaction (IIR) from the late adhesive phase. Posterior fossa bleeding, warranting prolonged surveillance, additional bleeding and ventriculitis might augment the risk and the severity of arachnoiditis. Copyright © 2018 Elsevier Ltd. All rights reserved.
T cell specific adaptor protein (TSAd) promotes interaction of Nck with Lck and SLP-76 in T cells.
Hem, Cecilie Dahl; Sundvold-Gjerstad, Vibeke; Granum, Stine; Koll, Lise; Abrahamsen, Greger; Buday, Laszlo; Spurkland, Anne
2015-07-11
The Lck and Src binding adaptor protein TSAd (T cell specific adaptor) regulates actin polymerization in T cells and endothelial cells. The molecular details as to how TSAd regulates this process remain to be elucidated. To identify novel interaction partners for TSAd, we used a scoring matrix-assisted ligand algorithm (SMALI), and found that the Src homology 2 (SH2) domain of the actin regulator Non-catalytic region of tyrosine kinase adaptor protein (Nck) potentially binds to TSAd phosphorylated on Tyr(280) (pTyr(280)) and pTyr(305). These predictions were confirmed by peptide array analysis, showing direct binding of recombinant Nck SH2 to both pTyr(280) and pTyr(305) on TSAd. In addition, the SH3 domains of Nck interacted with the proline rich region (PRR) of TSAd. Pull-down and immunoprecipitation experiments further confirmed the Nck-TSAd interactions through Nck SH2 and SH3 domains. In line with this Nck and TSAd co-localized in Jurkat cells as assessed by confocal microscopy and imaging flow cytometry. Co-immunoprecipitation experiments in Jurkat TAg cells lacking TSAd revealed that TSAd promotes interaction of Nck with Lck and SLP-76, but not Vav1. TSAd expressing Jurkat cells contained more polymerized actin, an effect dependent on TSAd exon 7, which includes interactions sites for both Nck and Lck. TSAd binds to and co-localizes with Nck. Expression of TSAd increases both Nck-Lck and Nck-SLP-76 interaction in T cells. Recruitment of Lck and SLP-76 to Nck by TSAd could be one mechanism by which TSAd promotes actin polymerization in activated T cells.
Lusková, Petra; Dráber, Petr
2004-01-01
Mast cells and basophils are major effector cells in the immunoglobulin E (IgE)-dependent allergic reactions as well as in the innate immunity. They are distributed throughout the body and, upon allergen exposure, are stimulated via the high affinity IgE receptor (FcepsilonRI) to release several pro-inflammatory mediators such as leukotrienes, immunoregulatory cytokines and histamine. FcepsilonRI-mediated signaling is initiated by tyrosine phosphorylation of FcepsilonRI subunits by Src family kinase Lyn, which is followed by an activation of Syk/Zap family kinase Syk. The activated kinases then in turn phosphorylate and activate other enzymes [phospholipase Cgamma (PLCgamma) isoforms, phosphatidylinositol-3 kinase (PI3K) isoforms, protein kinase C (PKC) isoforms, Bruton's tyrosine kinase (Btk) and others], adaptors [linker for activation of T cells (LAT), Cbl, Grb2 and others] and GTP exchange factors/GTPases (Vav, Ras, Rho, and others), and subsequently induce the mobilization of stored and extracellular Ca(2+). These and other biochemical events lead within seconds and minutes to the secretory response and later to the production of chemokines. This review is focused on the use of tyrosine kinase inhibitors specific for Src family kinases (PP1/PP2, SU6656 and CT5269), Syk kinase (piceatannol, ER-27319 and BAY 61-3606) and Btk (terreic acid and LFM-A13) for a modulation of FcepsilonRI-mediated signaling in mast cells. Potential use of the inhibitors in the treatment of inflammatory and allergy diseases as well as future directions in the development of highly specific tyrosine kinases inhibitors of new generations and their use in an intended modulation of mast cell signaling are discussed.
RHOG-DOCK1-RAC1 Signaling Axis Is Perturbed in DHEA-Induced Polycystic Ovary in Rat Model.
Ubba, Vaibhave; Soni, Upendra Kumar; Chadchan, Sangappa; Maurya, Vineet Kumar; Kumar, Vijay; Maurya, Ruchika; Chaturvedi, Himanshu; Singh, Rajender; Dwivedi, Anila; Jha, Rajesh Kumar
2017-05-01
The function of RHOG, a RAC1 activator, was explored in the ovary during ovarian follicular development and pathological conditions. With the help of immunoblotting and immunolocalization, we determined the expression and localization of RHOG in normal (estrous cycle) and polycystic ovaries using Sprague Dawley (SD) rat model. Employing polymerase chain reaction and flow cytometry, we analyzed the transcript and expression levels of downstream molecules of RHOG, DOCK1, and RAC1 in the polycystic ovarian syndrome (PCOS) ovary along with normal antral follicular theca and granulosa cells after dehydroepiandrosterone (DHEA) supplementation. The effect of RHOG knockdown on DOCK1, VAV, and RAC1 expression was evaluated in the human ovarian cells (SKOV3), theca cells, and granulosa cells from SD rats with the help of flow cytometry. Oocyte at secondary follicles along with stromal cells showed optimal expression of RHOG. Immunoblotting of RHOG revealed its maximum expression at diestrus and proestrus, which was downregulated at estrus stage. Mild immunostaining of RHOG was also present in the theca and granulosa cells of the secondary and antral follicles. Polycystic ovary exhibited weak immunostaining for RHOG and that was corroborated by immunoblotting-based investigations. RHOG effectors DOCK1 and ELMO1 were found reduced in the ovary in PCOS condition/DHEA. RHOG silencing reduced the expression of DOCK1 and RAC1 in the theca and granulosa cells from SD rat antral follicles and that was mirrored in the human ovarian cells. Collectively, RHOG can mediate signaling through downstream effectors DOCK1 and RAC1 during ovarian follicular development (theca and granulosa cells and oocyte), but DHEA downregulated them in the PCOS ovary.
Multi-Inhibitory Effects of A2A Adenosine Receptor Signaling on Neutrophil Adhesion Under Flow.
Yago, Tadayuki; Tsukamoto, Hiroki; Liu, Zhenghui; Wang, Ying; Thompson, Linda F; McEver, Rodger P
2015-10-15
A2A adenosine receptor (A2AAR) signaling negatively regulates inflammatory responses in many disease models, but the detailed mechanisms remain unclear. We used the selective A2AAR agonist, ATL313, to examine how A2AAR signaling affects human and murine neutrophil adhesion under flow. Treating neutrophils with ATL313 inhibited selectin-induced, β2 integrin-dependent slow rolling and chemokine-induced, β2 integrin-dependent arrest on ICAM-1. ATL313 inhibited selectin-induced β2 integrin extension, which supports slow rolling, and chemokine-induced hybrid domain "swing-out," which supports arrest. Furthermore, ATL313 inhibited integrin outside-in signaling as revealed by reduced neutrophil superoxide production and spreading on immobilized anti-β2 integrin Ab. ATL313 suppressed selectin-triggered activation of Src family kinases (SFKs) and p38 MAPK, chemokine-triggered activation of Ras-related protein 1, and β2 integrin-triggered activation of SFKs and Vav cytoskeletal regulatory proteins. ATL313 activated protein kinase A and its substrate C-terminal Src kinase, an inhibitor of SFKs. Treating neutrophils with a protein kinase A inhibitor blocked the actions of ATL313. In vivo, ATL313-treated neutrophils rolled faster and arrested much less frequently in postcapillary venules of the murine cremaster muscle after TNF-α challenge. Furthermore, ATL313 markedly suppressed neutrophil migration into the peritoneum challenged with thioglycollate. ATL313 did not affect A2AAR-deficient neutrophils, confirming its specificity. Our findings provide new insights into the anti-inflammatory mechanisms of A2AAR signaling and the potential utility of A2AAR agonists in inflammatory diseases. Copyright © 2015 by The American Association of Immunologists, Inc.
Multi-inhibitory effects of A2A adenosine receptor signaling on neutrophil adhesion under flow**
Yago, Tadayuki; Tsukamoto, Hiroki; Liu, Zhenghui; Wang, Ying; Thompson, Linda F.; McEver, Rodger P.
2015-01-01
A2A adenosine receptor (A2AAR) signaling negatively regulates inflammatory responses in many disease models, but the detailed mechanisms remain unclear. We used the selective A2AAR agonist, ATL313, to examine how A2AAR signaling affects human and murine neutrophil adhesion under flow. Treating neutrophils with ATL313 inhibited selectin-induced, β2 integrin-dependent slow rolling and chemokine-induced, β2 integrin-dependent arrest on ICAM-1. ATL313 inhibited selectin-induced β2 integrin extension, which supports slow rolling, and chemokine-induced hybrid domain “swing-out”, which supports arrest. Furthermore, ATL313 inhibited integrin outside-in signaling as revealed by reduced neutrophil superoxide production and spreading on immobilized anti-β2 integrin antibody. ATL313 suppressed selectin-triggered activation of Src family kinases (SFKs) and p38 MAPK, chemokine-triggered activation of Ras-related protein 1 (Rap1), and β2 integrin-triggered activation of SFKs and Vav cytoskeletal regulatory proteins. ATL313 activated protein kinase A (PKA) and its substrate C-terminal Src kinase (Csk), an inhibitor of SFKs. Treating neutrophils with a PKA inhibitor blocked the actions of ATL313. In vivo, ATL313-treated neutrophils rolled faster and arrested much less frequently in postcapillary venules of the murine cremaster muscle after TNF-α challenge. Furthermore, ATL313 markedly suppressed neutrophil migration into the peritoneum challenged with thioglycollate. ATL313 did not affect A2AAR-deficient neutrophils, confirming its specificity. Our findings provide new insights into the anti-inflammatory mechanisms of A2AAR signaling and the potential utility of A2AAR agonists in inflammatory diseases. PMID:26355151
Katsura, Akihiro; Suzuki, Hiroshi I; Ueno, Toshihide; Mihira, Hajime; Yamazaki, Tomoko; Yasuda, Takahiko; Watabe, Tetsuro; Mano, Hiroyuki; Yamada, Yoshitsugu; Miyazono, Kohei
2016-01-01
Transforming growth factor-β (TGF-β) plays central roles in endothelial-mesenchymal transition (EndMT) involved in development and pathogenesis. Although EndMT and epithelial-mesenchymal transition are similar processes, roles of microRNAs in EndMT are largely unknown. Here, we report that constitutively active microRNA-31 (miR-31) is a positive regulator of TGF-β-induced EndMT. Although the expression is not induced by TGF-β, miR-31 is required for induction of mesenchymal genes including α-SMA, actin reorganization and MRTF-A activation during EndMT. We identified VAV3, a regulator of actin remodeling and MRTF-A activity, as a miR-31 target. Global transcriptome analysis further showed that miR-31 positively regulates EndMT-associated unique secretory phenotype (EndMT-SP) characterized by induction of multiple inflammatory chemokines and cytokines including CCL17, CX3CL1, CXCL16, IL-6 and Angptl2. As a mechanism for this phenomenon, TGF-β and miR-31 suppress Stk40, a negative regulator of NF-κB pathway. Interestingly, TGF-β induces alternative polyadenylation (APA)-coupled miR-31-dependent Stk40 suppression without concomitant miR-31 induction, and APA-mediated exclusion of internal poly(A) sequence in Stk40 3'UTR enhances target efficiency of Stk40. Finally, miR-31 functions as a molecular hub to integrate TGF-β and TNF-α signaling to enhance EndMT. These data confirm that constitutively active microRNAs, as well as inducible microRNAs, serve as phenotypic modifiers interconnected with transcriptome dynamics during EndMT. © 2015 The Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.
Gyenge, Christina C; Tenstad, Olav; Wiig, Helge
2003-01-01
In order to estimate the magnitude of electrostatic exclusion provided by the fixed negative charges of the skin and muscle interstitia of rat in vivo we measured the distribution volumes of two differently charged albumin probes within these tissues. An implanted osmotic pump was used to reach and maintain a steady-state extracellular concentration of a mixture containing two iodine-labelled probes: a charged-modified human serum albumin, cHSA (i.e. a positive probe, isoelectirc point (pI) = 7.6) and a native human serum albumin, HSA (i.e. a normally charged, negative probe, pI = 5.0). Steady-state tissue concentrations were achieved after intravenous infusion of probes for 5–7 days. At the end of this period the animals were nephrectomized and a bolus of 51Cr-EDTA was administered for estimating the extracellular volume. Plasma volumes were measured as 5-min distribution volume of 125I-HSA in separate experiments. The steady-state interstitial fluid concentrations of all probes were determined using nylon wicks implanted postmortem. Calculations of labelled probes were made for interstitial fluid volumes (Vi), extravascular albumin distribution volumes (Vav,a) and relative interstitial excluded volume fractions (Vex,a/Vi). We found that the positive probe is excluded from a significantly smaller fraction of the interstitium. Specifically, the average relative albumin exclusion fractions obtained were: 16% and 26% in skeletal muscle and 30% and 40% in skin, for cHSA and HSA, respectively. On average, the fixed negative charges of the interstitium are responsible for about 40% of the total albumin exclusion in skeletal muscle and 25% in the whole skin tissue and thus, contribute significantly to volume exclusion in these tissues. PMID:12937287
Gyenge, Christina C; Tenstad, Olav; Wiig, Helge
2003-11-01
In order to estimate the magnitude of electrostatic exclusion provided by the fixed negative charges of the skin and muscle interstitia of rat in vivo we measured the distribution volumes of two differently charged albumin probes within these tissues. An implanted osmotic pump was used to reach and maintain a steady-state extracellular concentration of a mixture containing two iodine-labelled probes: a charged-modified human serum albumin, cHSA (i.e. a positive probe, isoelectirc point (pI) = 7.6) and a native human serum albumin, HSA (i.e. a normally charged, negative probe, pI = 5.0). Steady-state tissue concentrations were achieved after intravenous infusion of probes for 5-7 days. At the end of this period the animals were nephrectomized and a bolus of 51Cr-EDTA was administered for estimating the extracellular volume. Plasma volumes were measured as 5-min distribution volume of 125I-HSA in separate experiments. The steady-state interstitial fluid concentrations of all probes were determined using nylon wicks implanted postmortem. Calculations of labelled probes were made for interstitial fluid volumes (Vi), extravascular albumin distribution volumes (Vav,a) and relative interstitial excluded volume fractions (Vex,a/Vi). We found that the positive probe is excluded from a significantly smaller fraction of the interstitium. Specifically, the average relative albumin exclusion fractions obtained were: 16% and 26% in skeletal muscle and 30% and 40% in skin, for cHSA and HSA, respectively. On average, the fixed negative charges of the interstitium are responsible for about 40% of the total albumin exclusion in skeletal muscle and 25% in the whole skin tissue and thus, contribute significantly to volume exclusion in these tissues.
Wavelet filter analysis of local atmospheric pressure effects in the long-period tidal bands
NASA Astrophysics Data System (ADS)
Hu, X.-G.; Liu, L. T.; Ducarme, B.; Hsu, H. T.; Sun, H.-P.
2006-11-01
It is well known that local atmospheric pressure variations obviously affect the observation of short-period Earth tides, such as diurnal tides, semi-diurnal tides and ter-diurnal tides, but local atmospheric pressure effects on the long-period Earth tides have not been studied in detail. This is because the local atmospheric pressure is believed not to be sufficient for an effective pressure correction in long-period tidal bands, and there are no efficient methods to investigate local atmospheric effects in these bands. The usual tidal analysis software package, such as ETERNA, Baytap-G and VAV, cannot provide detailed pressure admittances for long-period tidal bands. We propose a wavelet method to investigate local atmospheric effects on gravity variations in long-period tidal bands. This method constructs efficient orthogonal filter bank with Daubechies wavelets of high vanishing moments. The main advantage of the wavelet filter bank is that it has excellent low frequency response and efficiently suppresses instrumental drift of superconducting gravimeters (SGs) without using any mathematical model. Applying the wavelet method to the 13-year continuous gravity observations from SG T003 in Brussels, Belgium, we filtered 12 long-period tidal groups into eight narrow frequency bands. Wavelet method demonstrates that local atmospheric pressure fluctuations are highly correlated with the noise of SG measurements in the period band 4-40 days with correlation coefficients higher than 0.95 and local atmospheric pressure variations are the main error source for the determination of the tidal parameters in these bands. We show the significant improvement of long-period tidal parameters provided by wavelet method in term of precision.
Levin, Theodore R; Corley, Douglas A; Jensen, Christopher D; Marks, Amy R; Zhao, Wei K; Zebrowski, Alexis M; Quinn, Virginia P; Browne, Lawrence W; Taylor, William R; Ahlquist, David A; Lidgard, Graham P; Berger, Barry M
2017-03-01
Fecal immunochemical test (FIT) screening detects most asymptomatic colorectal cancers. Combining FIT screening with stool-based genetic biomarkers increases sensitivity for cancer, but whether DNA biomarkers (biomarkers) differ for cancers detected versus missed by FIT screening has not been evaluated in a community-based population. To evaluate tissue biomarkers among Kaiser Permanente Northern California patients diagnosed with colorectal cancer within 2 years after FIT screening. FIT-negative and FIT-positive colorectal cancer patients 50-77 years of age were matched on age, sex, and cancer stage. Adequate DNA was isolated from paraffin-embedded specimens in 210 FIT-negative and 211 FIT-positive patients. Quantitative allele-specific real-time target and signal amplification assays were performed for 7 K-ras mutations and 10 aberrantly methylated DNA biomarkers (NDRG4, BMP3, SFMBT2_895, SFMBT2_896, SFMBT2_897, CHST2_7890, PDGFD, VAV3, DTX1, CHST2_7889). One or more biomarkers were found in 414 of 421 CRCs (98.3%). Biomarker expression was not associated with FIT status, with the exception of higher SFMBT2_897 expression in FIT-negative (194 of 210; 92.4%) than in FIT-positive cancers (180 of 211; 85.3%; p = 0.02). There were no consistent differences in biomarker expression by FIT status within age, sex, stage, and cancer location subgroups. The biomarkers of a currently in-use multi-target stool DNA test (K-ras, NDRG4, and BMP3) and eight newly characterized methylated biomarkers were commonly expressed in tumor tissue specimens, independent of FIT result. Additional study using stool-based testing with these new biomarkers will allow assessment of sensitivity, specificity, and clinical utility.
Delgado Tascón, Julia; Nyffenegger-Jann, Naja J.; Hauck, Christof R.
2012-01-01
Background CEACAM3 is a granulocyte receptor mediating the opsonin-independent recognition and phagocytosis of human-restricted CEACAM-binding bacteria. CEACAM3 function depends on an intracellular immunoreceptor tyrosine-based activation motif (ITAM)-like sequence that is tyrosine phosphorylated by Src family kinases upon receptor engagement. The phosphorylated ITAM-like sequence triggers GTP-loading of Rac by directly associating with the guanine nucleotide exchange factor (GEF) Vav. Rac stimulation in turn is critical for actin cytoskeleton rearrangements that generate lamellipodial protrusions and lead to bacterial uptake. Principal Findings In our present study we provide biochemical and microscopic evidence that the adaptor proteins Nck1 and Nck2, but not CrkL, Grb2 or SLP-76, bind to tyrosine phosphorylated CEACAM3. The association is phosphorylation-dependent and requires the Nck SH2 domain. Overexpression of the isolated Nck1 SH2 domain, RNAi-mediated knock-down of Nck1, or genetic deletion of Nck1 and Nck2 interfere with CEACAM3-mediated bacterial internalization and with the formation of lamellipodial protrusions. Nck is constitutively associated with WAVE2 and directs the actin nucleation promoting WAVE complex to tyrosine phosphorylated CEACAM3. In turn, dominant-negative WAVE2 as well as shRNA-mediated knock-down of WAVE2 or the WAVE-complex component Nap1 reduce internalization of bacteria. Conclusions Our results provide novel mechanistic insight into CEACAM3-initiated phagocytosis. We suggest that the CEACAM3 ITAM-like sequence is optimized to co-ordinate a minimal set of cellular factors needed to efficiently trigger actin-based lamellipodial protrusions and rapid pathogen engulfment. PMID:22448228
Pils, Stefan; Kopp, Kathrin; Peterson, Lisa; Delgado Tascón, Julia; Nyffenegger-Jann, Naja J; Hauck, Christof R
2012-01-01
CEACAM3 is a granulocyte receptor mediating the opsonin-independent recognition and phagocytosis of human-restricted CEACAM-binding bacteria. CEACAM3 function depends on an intracellular immunoreceptor tyrosine-based activation motif (ITAM)-like sequence that is tyrosine phosphorylated by Src family kinases upon receptor engagement. The phosphorylated ITAM-like sequence triggers GTP-loading of Rac by directly associating with the guanine nucleotide exchange factor (GEF) Vav. Rac stimulation in turn is critical for actin cytoskeleton rearrangements that generate lamellipodial protrusions and lead to bacterial uptake. In our present study we provide biochemical and microscopic evidence that the adaptor proteins Nck1 and Nck2, but not CrkL, Grb2 or SLP-76, bind to tyrosine phosphorylated CEACAM3. The association is phosphorylation-dependent and requires the Nck SH2 domain. Overexpression of the isolated Nck1 SH2 domain, RNAi-mediated knock-down of Nck1, or genetic deletion of Nck1 and Nck2 interfere with CEACAM3-mediated bacterial internalization and with the formation of lamellipodial protrusions. Nck is constitutively associated with WAVE2 and directs the actin nucleation promoting WAVE complex to tyrosine phosphorylated CEACAM3. In turn, dominant-negative WAVE2 as well as shRNA-mediated knock-down of WAVE2 or the WAVE-complex component Nap1 reduce internalization of bacteria. Our results provide novel mechanistic insight into CEACAM3-initiated phagocytosis. We suggest that the CEACAM3 ITAM-like sequence is optimized to co-ordinate a minimal set of cellular factors needed to efficiently trigger actin-based lamellipodial protrusions and rapid pathogen engulfment.
Sediment pollution of the Elbe River side structures - current research
NASA Astrophysics Data System (ADS)
Chalupova, Dagmar; Janský, Bohumír
2016-04-01
The contribution brings the summarized results of a long-term research on sediment pollution of side structures of the Elbe River over the last 14 years. The investigation has been focused on old anthropogenic pollution of sediment cores taken from fluvial lakes and floodplain, as the sampling of deeper sediments outside the riverbed is not a part of systematic monitoring of sediment pollution of the Elbe. The Elbe River floodplain has been influenced by human activities since the Middle Ages, but the main anthropogenic pollution have been produced in the 20th century. The studied localities were chosen with the respect to the distance from the source of industrial pollution, the intensity of hydrological communication with the river and the surrounding landuse to determine the extend and the level of anthropogenic contamination in the Elbe River floodplain ecosystem. Apart from bathymetric measurements, observation of the hydrological regime in several fluvial lakes or water quality sampling at some localities, the research was focused above all on determination of metal concentrations (Ag, Cd, Cr, Cu, Fe, Hg, Mn, Pb, Zn) in all taken sediment cores, specific organic compounds (PCBs, DDT, HCH, HCB, PAHs etc.), total organic carbon at some localities and grain structure analyses. The data were also compared with the results of systematic sediment monitoring from the nearest riverbed sampling stations on the Elbe River. The highest concentrations of metals and specific organic compounds were determined in the sediments taken from fluvial lakes and floodplain (Zimní přístav PARAMO, Rosice fuvial Lake, Libiš pool etc.) situated in the vicinity of the main Elbe River polluters - Synthesia chemical plant and PARAMO refinery in Pardubice or Spolana chemical plant near Neratovice. However, there was also determined a significant role of the hydrological communication with the river proved with lower sediment pollution in separated localities. The realization of the above mentioned research was possible thanks to the support of numerous Czech and German projects (GAUK, GAČR, SVV, VaV, PRVOUK, ELSA etc.).
Bunaciu, Rodica P.; LaTocha, Dorian H.; Varner, Jeffrey D.; Yen, Andrew
2015-01-01
6-Formylindolo(3,2-b)carbazole (FICZ) is a photoproduct of tryptophan and an endogenous high affinity ligand for aryl hydrocarbon receptor (AhR). It was previously reported that, in patient-derived HL-60 myeloblastic leukemia cells, retinoic acid (RA)-induced differentiation is driven by a signalsome containing c-Cbl and AhR. FICZ enhances RA-induced differentiation, assessed by expression of the membrane differentiation markers CD38 and CD11b, cell cycle arrest and the functional differentiation marker, inducible oxidative metabolism. Moreover, FICZ augments the expression of a number of the members of the RA-induced signalsome, such as c-Cbl, Vav1, Slp76, PI3K, and the Src family kinases Fgr and Lyn. Pursuing the molecular signaling responsible for RA-induced differentiation, we characterized, using FRET and clustering analysis, associations of key molecules thought to drive differentiation. Here we report that, assayed by FRET, AhR interacts with c-Cbl upon FICZ plus RA-induced differentiation, whereas AhR constitutively interacts with Cbl-b. Moreover, correlation analysis based on the flow cytometric assessment of differentiation markers and western blot detection of signaling factors reveal that Cbl-b, p-p38α and pT390-GSK3β, are not correlated with other known RA-induced signaling components or with a phenotypic outcome. We note that FICZ plus RA elicited signaling responses that were not typical of RA alone, but may represent alternative differentiation-driving pathways. In clusters of signaling molecules seminal to cell differentiation, FICZ co-administered with RA augments type and intensity of the dynamic changes induced by RA. Our data suggest relevance for FICZ in differentiation-induction therapy. The mechanism of action includes modulation of a SFK and MAPK centered signalsome and c-Cbl-AhR association. PMID:26287494
Xu, Ming; Li, Xiao-Xue; Ritter, Joseph K.; Abais, Justine M.; Zhang, Yang; Li, Pin-Lan
2013-01-01
The CD38-ADP-ribosylcyclase-mediated Ca2+ signaling pathway importantly contributes to the vasomotor response in different arteries. Although there is evidence indicating that the activation of CD38-ADP-ribosylcyclase is associated with CD38 internalization, the molecular mechanism mediating CD38 internalization and consequent activation in response to a variety of physiological and pathological stimuli remains poorly understood. Recent studies have shown that CD38 may sense redox signals and is thereby activated to produce cellular response and that the NADPH oxidase isoform, NOX1, is a major resource to produce superoxide (O2 ·−) in coronary arterial myocytes (CAMs) in response to muscarinic receptor agonist, which uses CD38-ADP-ribosylcyclase signaling pathway to exert its action in these CAMs. These findings led us hypothesize that NOX1-derived O2 ·− serves in an autocrine fashion to enhance CD38 internalization, leading to redox activation of CD38-ADP-ribosylcyclase activity in mouse CAMs. To test this hypothesis, confocal microscopy, flow cytometry and a membrane protein biotinylation assay were used in the present study. We first demonstrated that CD38 internalization induced by endothelin-1 (ET-1) was inhibited by silencing of NOX1 gene, but not NOX4 gene. Correspondingly, NOX1 gene silencing abolished ET-1-induced O2 ·− production and increased CD38-ADP-ribosylcyclase activity in CAMs, while activation of NOX1 by overexpression of Rac1 or Vav2 or administration of exogenous O2 ·− significantly increased CD38 internalization in CAMs. Lastly, ET-1 was found to markedly increase membrane raft clustering as shown by increased colocalization of cholera toxin-B with CD38 and NOX1. Taken together, these results provide direct evidence that Rac1-NOX1-dependent O2 ·− production mediates CD38 internalization in CAMs, which may represent an important mechanism linking receptor activation with CD38 activity in these cells. PMID:23940720
Barel, M; Le Romancer, M; Frade, R
2001-03-01
We previously demonstrated that CR2 activation on human B lymphocyte surface triggered tyrosine phosphorylation of a p95 component and its interaction with p85 subunit of phosphatidylinositol 3' (PI 3) kinase. Despite identical molecular mass of 95 kDa, this tyrosine phosphorylated p95 molecule was not CD19, the proto-oncogene Vav, or the adaptator Gab1. To identify this tyrosine phosphorylated p95 component, we first purified it by affinity chromatography on anti-phosphotyrosine mAb covalently linked to Sepharose 4B, followed by polyacrylamide gel electrophoresis. Then, the isolated 95-kDa tyrosine phosphorylated band was submitted to amino acid analysis by mass spectrometry; the two different isolated peptides were characterized by amino acid sequences 100% identical with two different domains of nucleolin, localized between aa 411--420 and 611--624. Anti-nucleolin mAb was used to confirm the antigenic properties of this p95 component. Functional studies demonstrated that CR2 activation induced, within a brief span of 2 min, tyrosine phosphorylation of nucleolin and its interaction with Src homology 2 domains of the p85 subunit of PI 3 kinase and of 3BP2 and Grb2, but not with Src homology 2 domains of Fyn and Gap. These properties of nucleolin were identical with those of the p95 previously described and induced by CR2 activation. Furthermore, tyrosine phosphorylation of nucleolin was also induced in normal B lymphocytes by CR2 activation but neither by CD19 nor BCR activation. These data support that tyrosine phosphorylation of nucleolin and its interaction with PI 3 kinase p85 subunit constitute one of the earlier steps in the specific intracellular signaling pathway of CR2.
MERTK interactions with SH2-domain proteins in the retinal pigment epithelium.
Shelby, Shameka J; Colwill, Karen; Dhe-Paganon, Sirano; Pawson, Tony; Thompson, Debra A
2013-01-01
The receptor tyrosine kinase MERTK plays an essential role in the phagocytic uptake of shed photoreceptor membranes by the retinal pigment epithelium (RPE). A fundamental aspect of signal transduction by receptor tyrosine kinases involves autophosphorylation of tyrosine residues that recruit Src-homology 2 (SH2)-domain proteins to the receptor intracellular domain. The goal of the current study was to evaluate the interactions of human MERTK with SH2-domain proteins present in the RPE. The MERTK intracellular domain was expressed as a 6xHis-fusion protein (6xHis-rMERTK(571-999)), purified and phosphorylated. Ni(2+)-NTA pull downs were performed using 6xHis-rMERTK(571-999) in incubations with recombinant phosphotyrosine-recognition sequences expressed as GST-fusion proteins. In addition, pull downs of native SH2-domain proteins were performed using 6xHis-rMERTK(571-999) and protein homogenates from rat RPE/choroid. For both recombinant and native proteins, western analysis detected MERTK interactions with GRB2, PIK3R1 (P85α), VAV3, and SRC. Immunohistochemical analysis localized each protein to mouse RPE. In cultured RPE-J cells incubated with rod outer segments (OS), siRNA knockdown of Grb2 had no effect on OS binding, but significantly reduced OS uptake. Pik3r1 localized to early phagosomes along with Rab5 and Eea1. Phosphorylation and activation of Src was detected downstream of phagocytosis and Mertk activation. These findings suggest that MERTK signaling in the RPE involves a cohort of SH2-domain proteins with the potential to regulate both cytoskeletal rearrangement and membrane movement. Identification of the SH2-domain signaling partners of MERTK is an important step toward further defining the mechanism of RPE phagocytosis that is central to the function and survival of the retina.
Rossi Paccani, Silvia; Benagiano, Marisa; Capitani, Nagaja; Zornetta, Irene; Ladant, Daniel; Montecucco, Cesare; D'Elios, Mario M.; Baldari, Cosima T.
2009-01-01
The adjuvanticity of bacterial adenylate cyclase toxins has been ascribed to their capacity, largely mediated by cAMP, to modulate APC activation, resulting in the expression of Th2–driving cytokines. On the other hand, cAMP has been demonstrated to induce a Th2 bias when present during T cell priming, suggesting that bacterial cAMP elevating toxins may directly affect the Th1/Th2 balance. Here we have investigated the effects on human CD4+ T cell differentiation of two adenylate cyclase toxins, Bacillus anthracis edema toxin (ET) and Bordetella pertussis CyaA, which differ in structure, mode of cell entry, and subcellular localization. We show that low concentrations of ET and CyaA, but not of their genetically detoxified adenylate cyclase defective counterparts, potently promote Th2 cell differentiation by inducing expression of the master Th2 transcription factors, c-maf and GATA-3. We also present evidence that the Th2–polarizing concentrations of ET and CyaA selectively inhibit TCR–dependent activation of Akt1, which is required for Th1 cell differentiation, while enhancing the activation of two TCR–signaling mediators, Vav1 and p38, implicated in Th2 cell differentiation. This is at variance from the immunosuppressive toxin concentrations, which interfere with the earliest step in TCR signaling, activation of the tyrosine kinase Lck, resulting in impaired CD3ζ phosphorylation and inhibition of TCR coupling to ZAP-70 and Erk activation. These results demonstrate that, notwithstanding their differences in their intracellular localization, which result in focalized cAMP production, both toxins directly affect the Th1/Th2 balance by interfering with the same steps in TCR signaling, and suggest that their adjuvanticity is likely to result from their combined effects on APC and CD4+ T cells. Furthermore, our results strongly support the key role of cAMP in the adjuvanticity of these toxins. PMID:19266022
Proaño-Bolaños, Carolina; Zhou, Mei; Wang, Lei; Coloma, Luis A; Chen, Tianbao; Shaw, Chris
2016-09-02
Phyllomedusine frogs are an extraordinary source of biologically active peptides. At least 8 families of antimicrobial peptides have been reported in this frog clade, the dermaseptins being the most diverse. By a peptidomic approach, integrating molecular cloning, Edman degradation sequencing and tandem mass spectrometry, a new family of antimicrobial peptides has been identified in Cruziohyla calcarifer. These 15 novel antimicrobial peptides of 20-32 residues in length are named cruzioseptins. They are characterized by having a unique shared N-terminal sequence GFLD- and the sequence motifs -VALGAVSK- or -GKAAL(N/G/S) (V/A)V- in the middle of the peptide. Cruzioseptins have a broad spectrum of antimicrobial activity and low haemolytic effect. The most potent cruzioseptin was CZS-1 that had a MIC of 3.77μM against the Gram positive bacterium, Staphylococcus aureus and the yeast Candida albicans. In contrast, CZS-1 was 3-fold less potent against the Gram negative bacterium, Escherichia coli (MIC 15.11μM). CZS-1 reached 100% haemolysis at 120.87μM. Skin secretions from unexplored species such as C. calcarifer continue to demonstrate the enormous molecular diversity hidden in the amphibian skin. Some of these novel peptides may provide lead structures for the development of a new class of antibiotics and antifungals of therapeutic use. Through the combination of molecular cloning, Edman degradation sequencing, tandem mass spectrometry and MALDI-TOF MS we have identified a new family of 15 antimicrobial peptides in the skin secretion of Cruziohyla calcarifer. The novel family is named "Cruzioseptins" and contains cationic amphipathic peptides of 20-32 residues. They have a broad range of antimicrobial activity that also includes effective antifungals with low haemolytic activity. Therefore, C. calcarifer has proven to be a rich source of novel peptides, which could become leading structures for the development of novel antibiotics and antifungals of clinical application. Copyright © 2016 Elsevier B.V. All rights reserved.
Fraser, Heather I.; Howlett, Sarah; Clark, Jan; Rainbow, Daniel B.; Stanford, Stephanie M.; Wu, Dennis J.; Hsieh, Yi-Wen; Maine, Christian J.; Christensen, Mikkel; Kuchroo, Vijay; Sherman, Linda A.; Podolin, Patricia L.; Todd, John A.; Steward, Charles A.; Peterson, Laurence B.; Bottini, Nunzio
2015-01-01
By congenic strain mapping using autoimmune NOD.C57BL/6J congenic mice, we demonstrated previously that the type 1 diabetes (T1D) protection associated with the insulin-dependent diabetes (Idd)10 locus on chromosome 3, originally identified by linkage analysis, was in fact due to three closely linked Idd loci: Idd10, Idd18.1, and Idd18.3. In this study, we define two additional Idd loci—Idd18.2 and Idd18.4—within the boundaries of this cluster of disease-associated genes. Idd18.2 is 1.31 Mb and contains 18 genes, including Ptpn22, which encodes a phosphatase that negatively regulates T and B cell signaling. The human ortholog of Ptpn22, PTPN22, is associated with numerous autoimmune diseases, including T1D. We, therefore, assessed Ptpn22 as a candidate for Idd18.2; resequencing of the NOD Ptpn22 allele revealed 183 single nucleotide polymorphisms with the C57BL/6J (B6) allele—6 exonic and 177 intronic. Functional studies showed higher expression of full-length Ptpn22 RNA and protein, and decreased TCR signaling in congenic strains with B6-derived Idd18.2 susceptibility alleles. The 953-kb Idd18.4 locus contains eight genes, including the candidate Cd2. The CD2 pathway is associated with the human autoimmune disease, multiple sclerosis, and mice with NOD-derived susceptibility alleles at Idd18.4 have lower CD2 expression on B cells. Furthermore, we observed that susceptibility alleles at Idd18.2 can mask the protection provided by Idd10/Cd101 or Idd18.1/Vav3 and Idd18.3. In summary, we describe two new T1D loci, Idd18.2 and Idd18.4, candidate genes within each region, and demonstrate the complex nature of genetic interactions underlying the development of T1D in the NOD mouse model. PMID:26438525
Role of phosphoinositide 3-kinase regulatory isoforms in development and actin rearrangement.
Brachmann, Saskia M; Yballe, Claudine M; Innocenti, Metello; Deane, Jonathan A; Fruman, David A; Thomas, Sheila M; Cantley, Lewis C
2005-04-01
Class Ia phosphoinositide 3-kinases (PI3Ks) are heterodimers of p110 catalytic and p85 regulatory subunits that mediate a variety of cellular responses to growth and differentiation factors. Although embryonic development is not impaired in mice lacking all isoforms of the p85alpha gene (p85alpha-/- p55alpha-/- p50alpha-/-) or in mice lacking the p85beta gene (p85beta-/-) (D. A. Fruman, F. Mauvais-Jarvis, D. A. Pollard, C. M. Yballe, D. Brazil, R. T. Bronson, C. R. Kahn, and L. C. Cantley, Nat Genet. 26:379-382, 2000; K. Ueki, C. M. Yballe, S. M. Brachmann, D. Vicent, J. M. Watt, C. R. Kahn, and L. C. Cantley, Proc. Natl. Acad. Sci. USA 99:419-424, 2002), we show here that loss of both genes results in lethality at embryonic day 12.5 (E12.5). The phenotypes of these embryos, including subepidermal blebs flanking the neural tube at E8 and bleeding into the blebs during the turning process, are similar to defects observed in platelet-derived growth factor receptor alpha null (PDGFRalpha-/-) mice (P. Soriano, Development 124:2691-2700, 1997), suggesting that PI3K is an essential mediator of PDGFRalpha signaling at this developmental stage. p85alpha-/- p55alpha+/+ p50alpha+/+ p85beta-/- mice had similar but less severe defects, indicating that p85alpha and p85beta have a critical and redundant function in development. Mouse embryo fibroblasts deficient in all p85alpha and p85beta gene products (p85alpha-/- p55alpha-/- p50alpha-/- p85beta-/-) are defective in PDGF-induced membrane ruffling. Overexpression of the Rac-specific GDP-GTP exchange factor Vav2 or reintroduction of p85alpha or p85beta rescues the membrane ruffling defect. Surprisingly, reintroduction of p50alpha also restored PDGF-dependent membrane ruffling. These results indicate that class Ia PI3K is critical for PDGF-dependent actin rearrangement but that the SH3 domain and the Rho/Rac/Cdc42-interacting domain of p85, which lacks p50alpha, are not required for this response.
Systems and Methods for Derivative-Free Adaptive Control
NASA Technical Reports Server (NTRS)
Calise, Anthony J. (Inventor); Yucelen, Tansel (Inventor); Kim, Kilsoo (Inventor)
2015-01-01
An adaptive control system is disclosed. The control system can control uncertain dynamic systems. The control system can employ one or more derivative-free adaptive control architectures. The control system can further employ one or more derivative-free weight update laws. The derivative-free weight update laws can comprise a time-varying estimate of an ideal vector of weights. The control system of the present invention can therefore quickly stabilize systems that undergo sudden changes in dynamics, caused by, for example, sudden changes in weight. Embodiments of the present invention can also provide a less complex control system than existing adaptive control systems. The control system can control aircraft and other dynamic systems, such as, for example, those with non-minimum phase dynamics.
Systems and Methods for Parameter Dependent Riccati Equation Approaches to Adaptive Control
NASA Technical Reports Server (NTRS)
Kim, Kilsoo (Inventor); Yucelen, Tansel (Inventor); Calise, Anthony J. (Inventor)
2015-01-01
Systems and methods for adaptive control are disclosed. The systems and methods can control uncertain dynamic systems. The control system can comprise a controller that employs a parameter dependent Riccati equation. The controller can produce a response that causes the state of the system to remain bounded. The control system can control both minimum phase and non-minimum phase systems. The control system can augment an existing, non-adaptive control design without modifying the gains employed in that design. The control system can also avoid the use of high gains in both the observer design and the adaptive control law.
Description of the SSF PMAD DC testbed control system data acquisition function
NASA Technical Reports Server (NTRS)
Baez, Anastacio N.; Mackin, Michael; Wright, Theodore
1992-01-01
The NASA LeRC in Cleveland, Ohio has completed the development and integration of a Power Management and Distribution (PMAD) DC Testbed. This testbed is a reduced scale representation of the end to end, sources to loads, Space Station Freedom Electrical Power System (SSF EPS). This unique facility is being used to demonstrate DC power generation and distribution, power management and control, and system operation techniques considered to be prime candidates for the Space Station Freedom. A key capability of the testbed is its ability to be configured to address system level issues in support of critical SSF program design milestones. Electrical power system control and operation issues like source control, source regulation, system fault protection, end-to-end system stability, health monitoring, resource allocation, and resource management are being evaluated in the testbed. The SSF EPS control functional allocation between on-board computers and ground based systems is evolving. Initially, ground based systems will perform the bulk of power system control and operation. The EPS control system is required to continuously monitor and determine the current state of the power system. The DC Testbed Control System consists of standard controllers arranged in a hierarchical and distributed architecture. These controllers provide all the monitoring and control functions for the DC Testbed Electrical Power System. Higher level controllers include the Power Management Controller, Load Management Controller, Operator Interface System, and a network of computer systems that perform some of the SSF Ground based Control Center Operation. The lower level controllers include Main Bus Switch Controllers and Photovoltaic Controllers. Power system status information is periodically provided to the higher level controllers to perform system control and operation. The data acquisition function of the control system is distributed among the various levels of the hierarchy. Data requirements are dictated by the control system algorithms being implemented at each level. A functional description of the various levels of the testbed control system architecture, the data acquisition function, and the status of its implementationis presented.
Component Control System for a Vehicle
NASA Technical Reports Server (NTRS)
Lee, Chunhao J. (Inventor); Fraser-Chanpong, Nathan (Inventor); Vitale, Robert L. (Inventor); Akinyode, Akinjide Akinniyi (Inventor); Dawson, Andrew D. (Inventor); Guo, Raymond (Inventor); Waligora, Thomas M. (Inventor); Spain, Ivan (Inventor); Bluethmann, William J. (Inventor); Reed, Ryan M. (Inventor)
2016-01-01
A vehicle includes a chassis, a modular component, and a central operating system. The modular component is supported by the chassis. The central operating system includes a component control system, a primary master controller, and a secondary master controller. The component control system is configured for controlling the modular component. The primary and secondary master controllers are in operative communication with the component control system. The primary and secondary master controllers are configured to simultaneously transmit commands to the component control system. The component control system is configured to accept commands from the secondary master controller only when a fault occurs in the primary master controller.
Supervisory Control and Data Acquisition System | Energy Systems
Integration Facility | NREL Supervisory Control and Data Acquisition System Supervisory Control supervisory control and data acquisition (SCADA) system monitors and controls safety systems and gathers real Energy Systems Integration Facility control room. The Energy Systems Integration Facility's SCADA system
Development of similarity theory for control systems
NASA Astrophysics Data System (ADS)
Myshlyaev, L. P.; Evtushenko, V. F.; Ivushkin, K. A.; Makarov, G. V.
2018-05-01
The area of effective application of the traditional similarity theory and the need necessity of its development for systems are discussed. The main statements underlying the similarity theory of control systems are given. The conditions for the similarity of control systems and the need for similarity control control are formulated. Methods and algorithms for estimating and similarity control of control systems and the results of research of control systems based on their similarity are presented. The similarity control of systems includes the current evaluation of the degree of similarity of control systems and the development of actions controlling similarity, and the corresponding targeted change in the state of any element of control systems.
Temperature Control. Honeywell Planning Guide.
ERIC Educational Resources Information Center
Honeywell, Inc., Minneapolis, Minn.
Presents planning considerations in selecting proper temperature control systems. Various aspects are discussed including--(1) adequate environmental control, (2) adequate control area, (3) control system design, (4) operators rate their systems, (5) type of control components, (6) basic control system, (7) automatic control systems, and (8)…
Performance of Control System Using Microcontroller for Sea Water Circulation
NASA Astrophysics Data System (ADS)
Indriani, A.; Witanto, Y.; Pratama, A. S.; Supriyadi; Hendra; Tanjung, A.
2018-02-01
Now a day control system is very important rule for any process. Control system have been used in the automatic system. Automatic system can be seen in the industrial filed, mechanical field, electrical field and etc. In industrial and mechanical field, control system are used for control of motion component such as motor, conveyor, machine, control of process made of product, control of system and soon. In electrical field, control system can met for control of electrical system as equipment or part electrical like fan, rice cooker, refrigerator, air conditioner and etc. Control system are used for control of temperature and circulation gas, air and water. Control system of temperature and circulation of water also can be used for fisher community. Control system can be create by using microcontroller, PLC and other automatic program [1][2]. In this paper we will focus on the close loop system by using microcontroller Arduino Mega to control of temperature and circulation of sea water for fisher community. Performance control system is influenced by control equipment, sensor sensitivity, test condition, environment and others. The temperature sensor is measured using the DS18S20 and the sea water clarity sensor for circulation indicator with turbidity sensor. From the test results indicated that this control system can circulate sea water and maintain the temperature and clarity of seawater in a short time.
An adaptive control system for a shell-and-tube heat exchanger
NASA Astrophysics Data System (ADS)
Skorospeshkin, M. V.; Sukhodoev, M. S.; Skorospeshkin, V. N.; Rymashevskiy, P. O.
2017-01-01
This article suggests an adaptive control system for a hydrocarbon perspiration temperature control. This control system consists of a PI-controller and a pseudolinear compensating device that modifies control system dynamic properties. As a result, the behaviour research of the developed temperature control system has been undertaken. This article shows high effectiveness of the represented adaptive control system during changing control object parameters.
Mechanization of and experience with a triplex fly-by-wire backup control system
NASA Technical Reports Server (NTRS)
Lock, W. P.; Petersen, W. R.; Whitman, G. B.
1976-01-01
A redundant three axis analog control system was designed and developed to back up a digital fly by wire control system for an F-8C airplane. The mechanization and operational experience with the backup control system, the problems involved in synchronizing it with the primary system, and the reliability of the system are discussed. The backup control system was dissimilar to the primary system, and it provided satisfactory handling through the flight envelope evaluated. Limited flight tests of a variety of control tasks showed that control was also satisfactory when the backup control system was controlled by a minimum displacement (force) side stick. The operational reliability of the F-8 digital fly by wire control system was satisfactory, with no unintentional downmodes to the backup control system in flight. The ground and flight reliability of the system's components is discussed.
Precision digital control systems
NASA Astrophysics Data System (ADS)
Vyskub, V. G.; Rozov, B. S.; Savelev, V. I.
This book is concerned with the characteristics of digital control systems of great accuracy. A classification of such systems is considered along with aspects of stabilization, programmable control applications, digital tracking systems and servomechanisms, and precision systems for the control of a scanning laser beam. Other topics explored are related to systems of proportional control, linear devices and methods for increasing precision, approaches for further decreasing the response time in the case of high-speed operation, possibilities for the implementation of a logical control law, and methods for the study of precision digital control systems. A description is presented of precision automatic control systems which make use of electronic computers, taking into account the existing possibilities for an employment of computers in automatic control systems, approaches and studies required for including a computer in such control systems, and an analysis of the structure of automatic control systems with computers. Attention is also given to functional blocks in the considered systems.
NASA Astrophysics Data System (ADS)
Schaller, S. C.; Bjorklund, E. A.; Carr, G. P.; Faucett, J. A.; Oothoudt, M. A.
1997-05-01
The Los Alamos Neutron Scattering Center (LANSCE) Proton Storage Ring (PSR) control system upgrade was completed in 1996. In previous work, much of a PDP-11-based control system was replaced with Experimental Physics and Industrial Control System (EPICS) controls. Several parts of the old control system which used a VAX for operator displays and direct access to a CAMAC serial highway still remained. The old system was preserved as a "fallback" if the new EPICS-based system had problems. The control system upgrade completion included conversion of several application programs to EPICS-based operator interfaces, moving some data acquisition hardware to EPICS Input-Output Controllers (IOCs), and the implementation of new gateway software to complete the overall control system interoperability. Many operator interface (OPI) screens, written by LANSCE operators, have been incorporated in the new system. The old PSR control system hardware was removed. The robustness and reliability of the new controls obviated the need for a fallback capability.
Wilson, David G [Tijeras, NM; Robinett, III, Rush D.
2012-02-21
A control system design method and concomitant control system comprising representing a physical apparatus to be controlled as a Hamiltonian system, determining elements of the Hamiltonian system representation which are power generators, power dissipators, and power storage devices, analyzing stability and performance of the Hamiltonian system based on the results of the determining step and determining necessary and sufficient conditions for stability of the Hamiltonian system, creating a stable control system based on the results of the analyzing step, and employing the resulting control system to control the physical apparatus.
NASA Technical Reports Server (NTRS)
Tolivar, A. F.; Key, R. W.
1980-01-01
The attitude control performance of the solar electric propulsion system (SEPS) was evaluated. A thrust vector control system for powered flight control was examined along with a gas jet reaction control system, and a reaction wheel system, both of which have been proposed for nonpowered flight control. Comprehensive computer simulations of each control system were made and evaluated using a 30 mode spacecraft model. Results obtained indicate that thrust vector control and reaction wheel systems offer acceptable smooth proportional control. The gas jet control system is shown to be risky for a flexible structure such as SEPS, and is therefore, not recommended as a primary control method.
46 CFR 63.20-1 - Specific control system requirements.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 2 2011-10-01 2011-10-01 false Specific control system requirements. 63.20-1 Section 63... AUXILIARY BOILERS Additional Control System Requirements § 63.20-1 Specific control system requirements. In... following requirements apply for specific control systems: (a) Primary safety control system. Following...
46 CFR 63.20-1 - Specific control system requirements.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 2 2010-10-01 2010-10-01 false Specific control system requirements. 63.20-1 Section 63... AUXILIARY BOILERS Additional Control System Requirements § 63.20-1 Specific control system requirements. In... following requirements apply for specific control systems: (a) Primary safety control system. Following...
NASA Astrophysics Data System (ADS)
Wu, Jiang; Liao, Fucheng; Tomizuka, Masayoshi
2017-01-01
This paper discusses the design of the optimal preview controller for a linear continuous-time stochastic control system in finite-time horizon, using the method of augmented error system. First, an assistant system is introduced for state shifting. Then, in order to overcome the difficulty of the state equation of the stochastic control system being unable to be differentiated because of Brownian motion, the integrator is introduced. Thus, the augmented error system which contains the integrator vector, control input, reference signal, error vector and state of the system is reconstructed. This leads to the tracking problem of the optimal preview control of the linear stochastic control system being transformed into the optimal output tracking problem of the augmented error system. With the method of dynamic programming in the theory of stochastic control, the optimal controller with previewable signals of the augmented error system being equal to the controller of the original system is obtained. Finally, numerical simulations show the effectiveness of the controller.
14 CFR 27.395 - Control system.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Control system. 27.395 Section 27.395... STANDARDS: NORMAL CATEGORY ROTORCRAFT Strength Requirements Control Surface and System Loads § 27.395 Control system. (a) The part of each control system from the pilot's controls to the control stops must be...
Mechanization of and experience with a triplex fly-by-wire backup control system
NASA Technical Reports Server (NTRS)
Lock, W. P.; Petersen, W. R.; Whitman, G. B.
1975-01-01
A redundant three-axis analog control system was designed and developed to back up a digital fly-by-wire control system for an F-8C airplane. Forty-two flights, involving 58 hours of flight time, were flown by six pilots. The mechanization and operational experience with the backup control system, the problems involved in synchronizing it with the primary system, and the reliability of the system are discussed. The backup control system was dissimilar to the primary system, and it provided satisfactory handling through the flight envelope evaluated. Limited flight tests of a variety of control tasks showed that control was also satisfactory when the backup control system was controlled by a minimum-displacement (force) side stick. The operational reliability of the F-8 digital fly-by-wire control system was satisfactory, with no unintentional downmodes to the backup control system in flight. The ground and flight reliability of the system's components is discussed.
14 CFR 23.685 - Control system details.
Code of Federal Regulations, 2010 CFR
2010-01-01
... Control Systems § 23.685 Control system details. (a) Each detail of each control system must be designed... cables or tubes against other parts. (d) Each element of the flight control system must have design... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Control system details. 23.685 Section 23...
14 CFR 23.685 - Control system details.
Code of Federal Regulations, 2011 CFR
2011-01-01
... Control Systems § 23.685 Control system details. (a) Each detail of each control system must be designed... cables or tubes against other parts. (d) Each element of the flight control system must have design... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Control system details. 23.685 Section 23...
14 CFR 23.685 - Control system details.
Code of Federal Regulations, 2013 CFR
2013-01-01
... Control Systems § 23.685 Control system details. (a) Each detail of each control system must be designed... cables or tubes against other parts. (d) Each element of the flight control system must have design... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Control system details. 23.685 Section 23...
14 CFR 23.685 - Control system details.
Code of Federal Regulations, 2014 CFR
2014-01-01
... Control Systems § 23.685 Control system details. (a) Each detail of each control system must be designed... cables or tubes against other parts. (d) Each element of the flight control system must have design... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Control system details. 23.685 Section 23...
14 CFR 23.685 - Control system details.
Code of Federal Regulations, 2012 CFR
2012-01-01
... Control Systems § 23.685 Control system details. (a) Each detail of each control system must be designed... cables or tubes against other parts. (d) Each element of the flight control system must have design... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Control system details. 23.685 Section 23...
Summary of compliant and multi-arm control at NASA. Langley Research Center
NASA Technical Reports Server (NTRS)
Harrison, Fenton W.
1992-01-01
The topics are presented in viewgraph form and include the: single arm system, single arm axis system, single arm control systems, single arm hand controller axis system, single arm position axis system, single arm vision axis system, single arm force axis system, multi-arm system, multi-arm axis system, and the dual arm hand control axis system with control signals.
Underwater hydraulic shock shovel control system
NASA Astrophysics Data System (ADS)
Liu, He-Ping; Luo, A.-Ni; Xiao, Hai-Yan
2008-06-01
The control system determines the effectiveness of an underwater hydraulic shock shovel. This paper begins by analyzing the working principles of these shovels and explains the importance of their control systems. A new type of control system’s mathematical model was built and analyzed according to those principles. Since the initial control system’s response time could not fulfill the design requirements, a PID controller was added to the control system. System response time was still slower than required, so a neural network was added to nonlinearly regulate the proportional element, integral element and derivative element coefficients of the PID controller. After these improvements to the control system, system parameters fulfilled the design requirements. The working performance of electrically-controlled parts such as the rapidly moving high speed switch valve is largely determined by the control system. Normal control methods generally can’t satisfy a shovel’s requirements, so advanced and normal control methods were combined to improve the control system, bringing good results.
Energy Systems Integration Facility Control Room | Energy Systems
Integration Facility | NREL Energy Systems Integration Facility Control Room Energy Systems Integration Facility Control Room The Energy Systems Integration Facility control room allows system engineers as the monitoring point for the facility's integrated safety and control systems. Photo of employees
Research on Integrated Control of Microgrid Operation Mode
NASA Astrophysics Data System (ADS)
Cheng, ZhiPing; Gao, JinFeng; Li, HangYu
2018-03-01
The mode switching control of microgrid is the focus of its system control. According to the characteristics of different control, an integrated control system is put forward according to the detecting voltage and frequency deviation after switching of microgrid operating mode. This control system employs master-slave and peer-to-peer control. Wind turbine and photovoltaic(PV) adopt P/Q control, so the maximum power output can be achieved. The energy storage will work under the droop control if the system is grid-connected. When the system is off-grid, whether to employ droop control or P/f control is determined by system status. The simulation has been done and the system performance can meet the requirement.
Model and Study on Cascade Control System Based on IGBT Chopping Control
NASA Astrophysics Data System (ADS)
Niu, Yuxin; Chen, Liangqiao; Wang, Shuwen
2018-01-01
Thyristor cascade control system has a wide range of applications in the industrial field, but the traditional cascade control system has some shortcomings, such as a low power factor, serious harmonic pollution. In this paper, not only analyzing its system structure and working principle, but also discussing the two main factors affecting the power factor. Chopping-control cascade control system, adopted a new power switching device IGBT, which could overcome traditional cascade control system’s two main drawbacks efficiently. The basic principle of this cascade control system is discussed in this paper and the model of speed control system is built by using MATLAB/Simulink software. Finally, the simulation results of the system shows that the system works efficiently. This system is worthy to be spread widely in engineering application.
Adaptive control system having hedge unit and related apparatus and methods
NASA Technical Reports Server (NTRS)
Johnson, Eric Norman (Inventor); Calise, Anthony J. (Inventor)
2003-01-01
The invention includes an adaptive control system used to control a plant. The adaptive control system includes a hedge unit that receives at least one control signal and a plant state signal. The hedge unit generates a hedge signal based on the control signal, the plant state signal, and a hedge model including a first model having one or more characteristics to which the adaptive control system is not to adapt, and a second model not having the characteristic(s) to which the adaptive control system is not to adapt. The hedge signal is used in the adaptive control system to remove the effect of the characteristic from a signal supplied to an adaptation law unit of the adaptive control system so that the adaptive control system does not adapt to the characteristic in controlling the plant.
Active optical control system design of the SONG-China Telescope
NASA Astrophysics Data System (ADS)
Ye, Yu; Kou, Songfeng; Niu, Dongsheng; Li, Cheng; Wang, Guomin
2012-09-01
The standard SONG node structure of control system is presented. The active optical control system of the project is a distributed system, and a host computer and a slave intelligent controller are included. The host control computer collects the information from wave front sensor and sends commands to the slave computer to realize a closed loop model. For intelligent controller, a programmable logic controller (PLC) system is used. This system combines with industrial personal computer (IPC) and PLC to make up a control system with powerful and reliable.
78 FR 24368 - Airworthiness Directives; Bell Helicopter Textron, Inc. (Bell) Model Helicopters
Federal Register 2010, 2011, 2012, 2013, 2014
2013-04-25
... chain and cable control system with a push-pull control system. Since we issued that AD, we have... requires replacing the existing chain and cable control system with a push-pull control system. Both... Model 205A-1 to replace the tail rotor chain and cable control system with a push-pull control system...
Automotive Stirling engine system component review
NASA Technical Reports Server (NTRS)
Hindes, Chip; Stotts, Robert
1987-01-01
The design and testing of the power and combustion control system for the basic Stirling engine, Mod II, are examined. The power control system is concerned with transparent operation, and the Mod II uses engine working gas pressure variation to control the power output of the engine. The main components of the power control system, the power control valve, the pump-down system, and the hydrogen stable system, are described. The combustion control system consists of a combustion air supply system and an air/fuel ratio control system, and the system is to maintain constant heater head temperature, and to maximize combustion efficiency and to minimize exhaust emissions.
Networked event-triggered control: an introduction and research trends
NASA Astrophysics Data System (ADS)
Mahmoud, Magdi S.; Sabih, Muhammad
2014-11-01
A physical system can be studied as either continuous time or discrete-time system depending upon the control objectives. Discrete-time control systems can be further classified into two categories based on the sampling: (1) time-triggered control systems and (2) event-triggered control systems. Time-triggered systems sample states and calculate controls at every sampling instant in a periodic fashion, even in cases when states and calculated control do not change much. This indicates unnecessary and useless data transmission and computation efforts of a time-triggered system, thus inefficiency. For networked systems, the transmission of measurement and control signals, thus, cause unnecessary network traffic. Event-triggered systems, on the other hand, have potential to reduce the communication burden in addition to reducing the computation of control signals. This paper provides an up-to-date survey on the event-triggered methods for control systems and highlights the potential research directions.
Carrasco, Juan A; Dormido, Sebastián
2006-04-01
The use of industrial control systems in simulators facilitates the execution of engineering activities related with the installation and the optimization of the control systems in real plants. "Industrial control system" intends to be a valid term that would represent all the control systems which can be installed in an industrial plant, ranging from complex distributed control systems and SCADA packages to small single control devices. This paper summarizes the current alternatives for the development of simulators of industrial plants and presents an analysis of the process of integrating an industrial control system into a simulator, with the aim of helping in the installation of real control systems in simulators.
Weld Nugget Temperature Control in Thermal Stir Welding
NASA Technical Reports Server (NTRS)
Ding, R. Jeffrey (Inventor)
2014-01-01
A control system for a thermal stir welding system is provided. The control system includes a sensor and a controller. The sensor is coupled to the welding system's containment plate assembly and generates signals indicative of temperature of a region adjacent and parallel to the welding system's stir rod. The controller is coupled to the sensor and generates at least one control signal using the sensor signals indicative of temperature. The controller is also coupled to the welding system such that at least one of rotational speed of the stir rod, heat supplied by the welding system's induction heater, and feed speed of the welding system's weld material feeder are controlled based on the control signal(s).
Mansouri, Mohammad; Teshnehlab, Mohammad; Aliyari Shoorehdeli, Mahdi
2015-05-01
In this paper, a novel adaptive hierarchical fuzzy control system based on the variable structure control is developed for a class of SISO canonical nonlinear systems in the presence of bounded disturbances. It is assumed that nonlinear functions of the systems be completely unknown. Switching surfaces are incorporated into the hierarchical fuzzy control scheme to ensure the system stability. A fuzzy soft switching system decides the operation area of the hierarchical fuzzy control and variable structure control systems. All the nonlinearly appeared parameters of conclusion parts of fuzzy blocks located in different layers of the hierarchical fuzzy control system are adjusted through adaptation laws deduced from the defined Lyapunov function. The proposed hierarchical fuzzy control system reduces the number of rules and consequently the number of tunable parameters with respect to the ordinary fuzzy control system. Global boundedness of the overall adaptive system and the desired precision are achieved using the proposed adaptive control system. In this study, an adaptive hierarchical fuzzy system is used for two objectives; it can be as a function approximator or a control system based on an intelligent-classic approach. Three theorems are proven to investigate the stability of the nonlinear dynamic systems. The important point about the proposed theorems is that they can be applied not only to hierarchical fuzzy controllers with different structures of hierarchical fuzzy controller, but also to ordinary fuzzy controllers. Therefore, the proposed algorithm is more general. To show the effectiveness of the proposed method four systems (two mechanical, one mathematical and one chaotic) are considered in simulations. Simulation results demonstrate the validity, efficiency and feasibility of the proposed approach to control of nonlinear dynamic systems. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.
Hybrid supervisory control using recurrent fuzzy neural network for tracking periodic inputs.
Lin, F J; Wai, R J; Hong, C M
2001-01-01
A hybrid supervisory control system using a recurrent fuzzy neural network (RFNN) is proposed to control the mover of a permanent magnet linear synchronous motor (PMLSM) servo drive for the tracking of periodic reference inputs. First, the field-oriented mechanism is applied to formulate the dynamic equation of the PMLSM. Then, a hybrid supervisory control system, which combines a supervisory control system and an intelligent control system, is proposed to control the mover of the PMLSM for periodic motion. The supervisory control law is designed based on the uncertainty bounds of the controlled system to stabilize the system states around a predefined bound region. Since the supervisory control law will induce excessive and chattering control effort, the intelligent control system is introduced to smooth and reduce the control effort when the system states are inside the predefined bound region. In the intelligent control system, the RFNN control is the main tracking controller which is used to mimic a idea control law and a compensated control is proposed to compensate the difference between the idea control law and the RFNN control. The RFNN has the merits of fuzzy inference, dynamic mapping and fast convergence speed, In addition, an online parameter training methodology, which is derived using the Lyapunov stability theorem and the gradient descent method, is proposed to increase the learning capability of the RFNN. The proposed hybrid supervisory control system using RFNN can track various periodic reference inputs effectively with robust control performance.
CONTROL ROOM WITH SPRINKLER SYSTEM CONTROLS, INCLUDING MANUAL CONTROL BOXES ...
CONTROL ROOM WITH SPRINKLER SYSTEM CONTROLS, INCLUDING MANUAL CONTROL BOXES FOR THE VENTILATION SYSTEM AND A PLC SWITCH FOR AUTOMATIC CO (CARBON MONOXIDE) SYSTEM. THE AIR TESTING SYSTEM IS FREE STANDING AND THE FANS ARE COMPUTER-OPERATED. - Alaskan Way Viaduct and Battery Street Tunnel, Seattle, King County, WA
A New Design Method of Automotive Electronic Real-time Control System
NASA Astrophysics Data System (ADS)
Zuo, Wenying; Li, Yinguo; Wang, Fengjuan; Hou, Xiaobo
Structure and functionality of automotive electronic control system is becoming more and more complex. The traditional manual programming development mode to realize automotive electronic control system can't satisfy development needs. So, in order to meet diversity and speedability of development of real-time control system, combining model-based design approach and auto code generation technology, this paper proposed a new design method of automotive electronic control system based on Simulink/RTW. Fristly, design algorithms and build a control system model in Matlab/Simulink. Then generate embedded code automatically by RTW and achieve automotive real-time control system development in OSEK/VDX operating system environment. The new development mode can significantly shorten the development cycle of automotive electronic control system, improve program's portability, reusability and scalability and had certain practical value for the development of real-time control system.
40 CFR 63.746 - Standards: Depainting operations.
Code of Federal Regulations, 2012 CFR
2012-07-01
..., or paragraph (c) where organic HAP are controlled using a control system. This section does not apply... filter system, three-stage filter system, or other control system equivalent to the three-stage filter... operation shall be reduced by the use of a control system. Each control system that was installed before the...
40 CFR 63.746 - Standards: Depainting operations.
Code of Federal Regulations, 2014 CFR
2014-07-01
..., or paragraph (c) where organic HAP are controlled using a control system. This section does not apply... filter system, three-stage filter system, or other control system equivalent to the three-stage filter... operation shall be reduced by the use of a control system. Each control system that was installed before the...
40 CFR 63.746 - Standards: Depainting operations.
Code of Federal Regulations, 2013 CFR
2013-07-01
..., or paragraph (c) where organic HAP are controlled using a control system. This section does not apply... filter system, three-stage filter system, or other control system equivalent to the three-stage filter... operation shall be reduced by the use of a control system. Each control system that was installed before the...
40 CFR 63.746 - Standards: Depainting operations.
Code of Federal Regulations, 2010 CFR
2010-07-01
..., or paragraph (c) where organic HAP are controlled using a control system. This section does not apply... filter system, three-stage filter system, or other control system equivalent to the three-stage filter... operation shall be reduced by the use of a control system. Each control system that was installed before the...
Research on the man in the loop control system of the robot arm based on gesture control
NASA Astrophysics Data System (ADS)
Xiao, Lifeng; Peng, Jinbao
2017-03-01
The Man in the loop control system of the robot arm based on gesture control research complex real-world environment, which requires the operator to continuously control and adjust the remote manipulator, as the background, completes the specific mission human in the loop entire system as the research object. This paper puts forward a kind of robot arm control system of Man in the loop based on gesture control, by robot arm control system based on gesture control and Virtual reality scene feedback to enhance immersion and integration of operator, to make operator really become a part of the whole control loop. This paper expounds how to construct a man in the loop control system of the robot arm based on gesture control. The system is a complex system of human computer cooperative control, but also people in the loop control problem areas. The new system solves the problems that the traditional method has no immersion feeling and the operation lever is unnatural, the adjustment time is long, and the data glove mode wears uncomfortable and the price is expensive.
Experience with synchronous and asynchronous digital control systems
NASA Technical Reports Server (NTRS)
Regenie, V. A.; Chacon, C. V.; Lock, W. P.
1986-01-01
Flight control systems have undergone a revolution since the days of simple mechanical linkages; presently the most advanced systems are full-authority, full-time digital systems controlling unstable aircraft. With the use of advanced control systems, the aerodynamic design can incorporate features that allow greater performance and fuel savings, as can be seen on the new Airbus design and advanced tactical fighter concepts. These advanced aircraft will be and are relying on the flight control system to provide the stability and handling qualities required for safe flight and to allow the pilot to control the aircraft. Various design philosophies have been proposed and followed to investigate system architectures for these advanced flight control systems. One major area of discussion is whether a multichannel digital control system should be synchronous or asynchronous. This paper addressed the flight experience at the Dryden Flight Research Facility of NASA's Ames Research Center with both synchronous and asynchronous digital flight control systems. Four different flight control systems are evaluated against criteria such as software reliability, cost increases, and schedule delays.
Evolving Systems and Adaptive Key Component Control
NASA Technical Reports Server (NTRS)
Frost, Susan A.; Balas, Mark J.
2009-01-01
We propose a new framework called Evolving Systems to describe the self-assembly, or autonomous assembly, of actively controlled dynamical subsystems into an Evolved System with a higher purpose. An introduction to Evolving Systems and exploration of the essential topics of the control and stability properties of Evolving Systems is provided. This chapter defines a framework for Evolving Systems, develops theory and control solutions for fundamental characteristics of Evolving Systems, and provides illustrative examples of Evolving Systems and their control with adaptive key component controllers.
The Galileo scan platform pointing control system - A modern control theoretic viewpoint
NASA Technical Reports Server (NTRS)
Sevaston, G. E.; Macala, G. A.; Man, G. K.
1985-01-01
The current Galileo scan platform pointing control system (SPPCS) is described, and ways in which modern control concepts could serve to enhance it are considered. Of particular interest are: the multi-variable design model and overall control system architecture, command input filtering, feedback compensator and command input design, stability robustness constraint for both continuous time control systems and for sampled data control systems, and digital implementation of the control system. The proposed approach leads to the design of a system that is similar to current Galileo SPPCS configuration, but promises to be more systematic.
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.
Wireless sensing and vibration control with increased redundancy and robustness design.
Li, Peng; Li, Luyu; Song, Gangbing; Yu, Yan
2014-11-01
Control systems with long distance sensor and actuator wiring have the problem of high system cost and increased sensor noise. Wireless sensor network (WSN)-based control systems are an alternative solution involving lower setup and maintenance costs and reduced sensor noise. However, WSN-based control systems also encounter problems such as possible data loss, irregular sampling periods (due to the uncertainty of the wireless channel), and the possibility of sensor breakdown (due to the increased complexity of the overall control system). In this paper, a wireless microcontroller-based control system is designed and implemented to wirelessly perform vibration control. The wireless microcontroller-based system is quite different from regular control systems due to its limited speed and computational power. Hardware, software, and control algorithm design are described in detail to demonstrate this prototype. Model and system state compensation is used in the wireless control system to solve the problems of data loss and sensor breakdown. A positive position feedback controller is used as the control law for the task of active vibration suppression. Both wired and wireless controllers are implemented. The results show that the WSN-based control system can be successfully used to suppress the vibration and produces resilient results in the presence of sensor failure.
Solar Dynamic Power System Stability Analysis and Control
NASA Technical Reports Server (NTRS)
Momoh, James A.; Wang, Yanchun
1996-01-01
The objective of this research is to conduct dynamic analysis, control design, and control performance test of solar power system. Solar power system consists of generation system and distribution network system. A bench mark system is used in this research, which includes a generator with excitation system and governor, an ac/dc converter, six DDCU's and forty-eight loads. A detailed model is used for modeling generator. Excitation system is represented by a third order model. DDCU is represented by a seventh order system. The load is modeled by the combination of constant power and constant impedance. Eigen-analysis and eigen-sensitivity analysis are used for system dynamic analysis. The effects of excitation system, governor, ac/dc converter control, and the type of load on system stability are discussed. In order to improve system transient stability, nonlinear ac/dc converter control is introduced. The direct linearization method is used for control design. The dynamic analysis results show that these controls affect system stability in different ways. The parameter coordination of controllers are recommended based on the dynamic analysis. It is concluded from the present studies that system stability is improved by the coordination of control parameters and the nonlinear ac/dc converter control stabilize system oscillation caused by the load change and system fault efficiently.
Design and Analysis of Morpheus Lander Flight Control System
NASA Technical Reports Server (NTRS)
Jang, Jiann-Woei; Yang, Lee; Fritz, Mathew; Nguyen, Louis H.; Johnson, Wyatt R.; Hart, Jeremy J.
2014-01-01
The Morpheus Lander is a vertical takeoff and landing test bed vehicle developed to demonstrate the system performance of the Guidance, Navigation and Control (GN&C) system capability for the integrated autonomous landing and hazard avoidance system hardware and software. The Morpheus flight control system design must be robust to various mission profiles. This paper presents a design methodology for employing numerical optimization to develop the Morpheus flight control system. The design objectives include attitude tracking accuracy and robust stability with respect to rigid body dynamics and propellant slosh. Under the assumption that the Morpheus time-varying dynamics and control system can be frozen over a short period of time, the flight controllers are designed to stabilize all selected frozen-time control systems in the presence of parametric uncertainty. Both control gains in the inner attitude control loop and guidance gains in the outer position control loop are designed to maximize the vehicle performance while ensuring robustness. The flight control system designs provided herein have been demonstrated to provide stable control systems in both Draper Ares Stability Analysis Tool (ASAT) and the NASA/JSC Trick-based Morpheus time domain simulation.
Robust Operation of Tendon-Driven Robot Fingers Using Force and Position-Based Control Laws
NASA Technical Reports Server (NTRS)
Hargrave, Brian (Inventor); Abdallah, Muhammad E (Inventor); Reiland, Matthew J (Inventor); Diftler, Myron A (Inventor); Strawser, Philip A (Inventor); Platt, Jr., Robert J. (Inventor); Ihrke, Chris A. (Inventor)
2013-01-01
A robotic system includes a tendon-driven finger and a control system. The system controls the finger via a force-based control law when a tension sensor is available, and via a position-based control law when a sensor is not available. Multiple tendons may each have a corresponding sensor. The system selectively injects a compliance value into the position-based control law when only some sensors are available. A control system includes a host machine and a non-transitory computer-readable medium having a control process, which is executed by the host machine to control the finger via the force- or position-based control law. A method for controlling the finger includes determining the availability of a tension sensor(s), and selectively controlling the finger, using the control system, via the force or position-based control law. The position control law allows the control system to resist disturbances while nominally maintaining the initial state of internal tendon tensions.
Minimum Control Requirements for Advanced Life Support Systems
NASA Technical Reports Server (NTRS)
Boulange, Richard; Jones, Harry; Jones, Harry
2002-01-01
Advanced control technologies are not necessary for the safe, reliable and continuous operation of Advanced Life Support (ALS) systems. ALS systems can and are adequately controlled by simple, reliable, low-level methodologies and algorithms. The automation provided by advanced control technologies is claimed to decrease system mass and necessary crew time by reducing buffer size and minimizing crew involvement. In truth, these approaches increase control system complexity without clearly demonstrating an increase in reliability across the ALS system. Unless these systems are as reliable as the hardware they control, there is no savings to be had. A baseline ALS system is presented with the minimal control system required for its continuous safe reliable operation. This baseline control system uses simple algorithms and scheduling methodologies and relies on human intervention only in the event of failure of the redundant backup equipment. This ALS system architecture is designed for reliable operation, with minimal components and minimal control system complexity. The fundamental design precept followed is "If it isn't there, it can't fail".
NASA Technical Reports Server (NTRS)
Elliott, Kenny B.; Ugoletti, Roberto; Sulla, Jeff
1992-01-01
The evolution and optimization of a real-time digital control system is presented. The control system is part of a testbed used to perform focused technology research on the interactions of spacecraft platform and instrument controllers with the flexible-body dynamics of the platform and platform appendages. The control system consists of Computer Automated Measurement and Control (CAMAC) standard data acquisition equipment interfaced to a workstation computer. The goal of this work is to optimize the control system's performance to support controls research using controllers with up to 50 states and frame rates above 200 Hz. The original system could support a 16-state controller operating at a rate of 150 Hz. By using simple yet effective software improvements, Input/Output (I/O) latencies and contention problems are reduced or eliminated in the control system. The final configuration can support a 16-state controller operating at 475 Hz. Effectively the control system's performance was increased by a factor of 3.
Interaction of feel system and flight control system dynamics on lateral flying qualities
NASA Technical Reports Server (NTRS)
Bailey, Randall E.; Powers, Bruce G.; Shafer, Mary F.
1988-01-01
An investigation of feel system and flight control system dynamics on lateral flying qualities was conducted using the variable stability USAF NT-33 aircraft. Experimental variations in feel system natural frequency, force-deflection gradient, control system command architecture type, flight control system filter frequency, and control system delay were made. The experiment data include pilot ratings using the Cooper-Harper (1969) rating scale, pilot comments, and tracking performance statistic. Three test pilots served as evaluators. The data indicate that as the feel system natural frequency is reduced lateral flying qualities degrade. At the slowest feel system frequency, the closed-loop response becomes nonlinear with a 'bobweight' effect apparent in the feel system. Feel system influences were essentially independent of the control system architecture. The flying qualities influence due to the feel system was different than when the identical dynamic systenm was used as a flight control system element.
Verification and Validation Challenges for Adaptive Flight Control of Complex Autonomous Systems
NASA Technical Reports Server (NTRS)
Nguyen, Nhan T.
2018-01-01
Autonomy of aerospace systems requires the ability for flight control systems to be able to adapt to complex uncertain dynamic environment. In spite of the five decades of research in adaptive control, the fact still remains that currently no adaptive control system has ever been deployed on any safety-critical or human-rated production systems such as passenger transport aircraft. The problem lies in the difficulty with the certification of adaptive control systems since existing certification methods cannot readily be used for nonlinear adaptive control systems. Research to address the notion of metrics for adaptive control began to appear in the recent years. These metrics, if accepted, could pave a path towards certification that would potentially lead to the adoption of adaptive control as a future control technology for safety-critical and human-rated production systems. Development of certifiable adaptive control systems represents a major challenge to overcome. Adaptive control systems with learning algorithms will never become part of the future unless it can be proven that they are highly safe and reliable. Rigorous methods for adaptive control software verification and validation must therefore be developed to ensure that adaptive control system software failures will not occur, to verify that the adaptive control system functions as required, to eliminate unintended functionality, and to demonstrate that certification requirements imposed by regulatory bodies such as the Federal Aviation Administration (FAA) can be satisfied. This presentation will discuss some of the technical issues with adaptive flight control and related V&V challenges.
Dilution cycle control for an absorption refrigeration system
Reimann, Robert C.
1984-01-01
A dilution cycle control system for an absorption refrigeration system is disclosed. The control system includes a time delay relay for sensing shutdown of the absorption refrigeration system and for generating a control signal only after expiration of a preselected time period measured from the sensed shutdown of the absorption refrigeration system, during which the absorption refrigeration system is not restarted. A dilution cycle for the absorption refrigeration system is initiated in response to generation of a control signal by the time delay relay. This control system is particularly suitable for use with an absorption refrigeration system which is frequently cycled on and off since the time delay provided by the control system prevents needless dilution of the absorption refrigeration system when the system is turned off for only a short period of time and then is turned back on.
14 CFR 25.395 - Control system.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Control system. 25.395 Section 25.395... STANDARDS: TRANSPORT CATEGORY AIRPLANES Structure Control Surface and System Loads § 25.395 Control system. (a) Longitudinal, lateral, directional, and drag control system and their supporting structures must...
14 CFR 25.395 - Control system.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Control system. 25.395 Section 25.395... STANDARDS: TRANSPORT CATEGORY AIRPLANES Structure Control Surface and System Loads § 25.395 Control system. (a) Longitudinal, lateral, directional, and drag control system and their supporting structures must...
Control of solar energy systems
NASA Astrophysics Data System (ADS)
Sizov, Iu. M.; Zakhidov, R. A.; Baranov, V. G.
Two approaches to the control of large solar energy systems, i.e., programmed control and control systems relying on the use of orientation transducers and feedback, are briefly reviewed, with particular attention given to problems associated with these control systems. A new control system for large solar power plants is then proposed which is based on a combination of these approaches. The general design of the control system is shown and its principle of operation described. The efficiency and cost effectiveness of the approach proposed here are demonstrated.
Gas turbine engine control system
NASA Technical Reports Server (NTRS)
Idelchik, Michael S. (Inventor)
1991-01-01
A control system and method of controlling a gas turbine engine. The control system receives an error signal and processes the error signal to form a primary fuel control signal. The control system also receives at least one anticipatory demand signal and processes the signal to form an anticipatory fuel control signal. The control system adjusts the value of the anticipatory fuel control signal based on the value of the error signal to form an adjusted anticipatory signal and then the adjusted anticipatory fuel control signal and the primary fuel control signal are combined to form a fuel command signal.
Software control and system configuration management: A systems-wide approach
NASA Technical Reports Server (NTRS)
Petersen, K. L.; Flores, C., Jr.
1984-01-01
A comprehensive software control and system configuration management process for flight-crucial digital control systems of advanced aircraft has been developed and refined to insure efficient flight system development and safe flight operations. Because of the highly complex interactions among the hardware, software, and system elements of state-of-the-art digital flight control system designs, a systems-wide approach to configuration control and management has been used. Specific procedures are implemented to govern discrepancy reporting and reconciliation, software and hardware change control, systems verification and validation testing, and formal documentation requirements. An active and knowledgeable configuration control board reviews and approves all flight system configuration modifications and revalidation tests. This flexible process has proved effective during the development and flight testing of several research aircraft and remotely piloted research vehicles with digital flight control systems that ranged from relatively simple to highly complex, integrated mechanizations.
Implementation method of multi-terminal DC control system
NASA Astrophysics Data System (ADS)
Yi, Liu; Hao-Ran, Huang; Jun-Wen, Zhou; Hong-Guang, Guo; Yu-Yong, Zhou
2018-04-01
Currently the multi-terminal DC system (MTDC) has more stations. Each station needs operators to monitor and control the device. It needs much more operation and maintenance, low efficiency and small reliability; for the most important reason, multi-terminal DC system has complex control mode. If one of the stations has some problem, the control of the whole system should have problems. According to research of the characteristics of multi-terminal DC (VSC-MTDC) systems, this paper presents a strong implementation of the multi-terminal DC Supervisory Control and Data Acquisition (SCADA) system. This system is intelligent, can be networking, integration and intelligent. A master control system is added in each station to communication with the other stations to send current and DC voltage value to pole control system for each station. Based on the practical application and information feedback in the China South Power Grid research center VSC-MTDC project, this system is higher efficiency and save the cost on the maintenance of convertor station to improve the intelligent level and comprehensive effect. And because of the master control system, a multi-terminal system hierarchy coordination control strategy is formed, this make the control and protection system more efficiency and reliability.
Embedded Control System for Smart Walking Assistance Device.
Bosnak, Matevz; Skrjanc, Igor
2017-03-01
This paper presents the design and implementation of a unique control system for a smart hoist, a therapeutic device that is used in rehabilitation of walking. The control system features a unique human-machine interface that allows the human to intuitively control the system just by moving or rotating its body. The paper contains an overview of the complete system, including the design and implementation of custom sensors, dc servo motor controllers, communication interfaces and embedded-system based central control system. The prototype of the complete system was tested by conducting a 6-runs experiment on 11 subjects and results are showing that the proposed control system interface is indeed intuitive and simple to adopt by the user.
Implementation of EPICS based vacuum control system for variable energy cyclotron centre, Kolkata
NASA Astrophysics Data System (ADS)
Roy, Anindya; Bhole, R. B.; Nandy, Partha P.; Yadav, R. C.; Pal, Sarbajit; Roy, Amitava
2015-03-01
The vacuum system of the Room Temperature (K = 130) Cyclotron of Variable Energy Cyclotron Centre is comprised of vacuum systems of main machine and Beam Transport System. The vacuum control system is upgraded to a PLC based Automated system from the initial relay based Manual system. The supervisory control of the vacuum system is implemented in Experimental Physics and Industrial Control System (EPICS). An EPICS embedded ARM based vacuum gauge controller is developed to mitigate the requirement of vendor specific gauge controller for gauges and also for seamless integration of the gauge controllers with the control system. A set of MS-Windows ActiveX components with embedded EPICS Channel Access interface are developed to build operator interfaces with less complex programming and to incorporate typical Windows feature, e.g., user authentication, file handling, better fonts, colors, mouse actions etc. into the operator interfaces. The control parameters, monitoring parameters, and system interlocks of the system are archived in MySQL based EPICS MySQL Archiver developed indigenously. In this paper, we describe the architecture, the implementation details, and the performance of the system.
Implementation of EPICS based vacuum control system for variable energy cyclotron centre, Kolkata.
Roy, Anindya; Bhole, R B; Nandy, Partha P; Yadav, R C; Pal, Sarbajit; Roy, Amitava
2015-03-01
The vacuum system of the Room Temperature (K = 130) Cyclotron of Variable Energy Cyclotron Centre is comprised of vacuum systems of main machine and Beam Transport System. The vacuum control system is upgraded to a PLC based Automated system from the initial relay based Manual system. The supervisory control of the vacuum system is implemented in Experimental Physics and Industrial Control System (EPICS). An EPICS embedded ARM based vacuum gauge controller is developed to mitigate the requirement of vendor specific gauge controller for gauges and also for seamless integration of the gauge controllers with the control system. A set of MS-Windows ActiveX components with embedded EPICS Channel Access interface are developed to build operator interfaces with less complex programming and to incorporate typical Windows feature, e.g., user authentication, file handling, better fonts, colors, mouse actions etc. into the operator interfaces. The control parameters, monitoring parameters, and system interlocks of the system are archived in MySQL based EPICS MySQL Archiver developed indigenously. In this paper, we describe the architecture, the implementation details, and the performance of the system.
Klepiszewski, K; Schmitt, T G
2002-01-01
While conventional rule based, real time flow control of sewer systems is in common use, control systems based on fuzzy logic have been used only rarely, but successfully. The intention of this study is to compare a conventional rule based control of a combined sewer system with a fuzzy logic control by using hydrodynamic simulation. The objective of both control strategies is to reduce the combined sewer overflow volume by an optimization of the utilized storage capacities of four combined sewer overflow tanks. The control systems affect the outflow of four combined sewer overflow tanks depending on the water levels inside the structures. Both systems use an identical rule base. The developed control systems are tested and optimized for a single storm event which affects heterogeneously hydraulic load conditions and local discharge. Finally the efficiencies of the two different control systems are compared for two more storm events. The results indicate that the conventional rule based control and the fuzzy control similarly reach the objective of the control strategy. In spite of the higher expense to design the fuzzy control system its use provides no advantages in this case.
Application of control theory to dynamic systems simulation
NASA Technical Reports Server (NTRS)
Auslander, D. M.; Spear, R. C.; Young, G. E.
1982-01-01
The application of control theory is applied to dynamic systems simulation. Theory and methodology applicable to controlled ecological life support systems are considered. Spatial effects on system stability, design of control systems with uncertain parameters, and an interactive computing language (PARASOL-II) designed for dynamic system simulation, report quality graphics, data acquisition, and simple real time control are discussed.
14 CFR 29.395 - Control system.
Code of Federal Regulations, 2011 CFR
2011-01-01
... Control system. (a) The reaction to the loads prescribed in § 29.397 must be provided by— (1) The control... its limit of motion); (4) The attachment of the control system to the rotor blade pitch control horn... of its motion); and (5) The attachment of the control system to the control surface horn (with the...
14 CFR 29.395 - Control system.
Code of Federal Regulations, 2010 CFR
2010-01-01
... Control system. (a) The reaction to the loads prescribed in § 29.397 must be provided by— (1) The control... its limit of motion); (4) The attachment of the control system to the rotor blade pitch control horn... of its motion); and (5) The attachment of the control system to the control surface horn (with the...
Research flight-control system development for the F-18 high alpha research vehicle
NASA Technical Reports Server (NTRS)
Pahle, Joseph W.; Powers, Bruce; Regenie, Victoria; Chacon, Vince; Degroote, Steve; Murnyak, Steven
1991-01-01
The F-18 high alpha research vehicle was recently modified by adding a thrust vectoring control system. A key element in the modification was the development of a research flight control system integrated with the basic F-18 flight control system. Discussed here are design requirements, system development, and research utility of the resulting configuration as an embedded system for flight research in the high angle of attack regime. Particular emphasis is given to control system modifications and control law features required for high angle of attack flight. Simulation results are used to illustrate some of the thrust vectoring control system capabilities and predicted maneuvering improvements.
Experience with synchronous and asynchronous digital control systems. [for flight
NASA Technical Reports Server (NTRS)
Regenie, Victoria A.; Chacon, Claude V.; Lock, Wilton P.
1986-01-01
Flight control systems have undergone a revolution since the days of simple mechanical linkages; presently the most advanced systems are full-authority, full-time digital systems controlling unstable aircraft. With the use of advanced control systems, the aerodynamic design can incorporate features that allow greater performance and fuel savings, as can be seen on the new Airbus design and advanced tactical fighter concepts. These advanced aircraft will be and are relying on the flight control system to provide the stability and handling qualities required for safe flight and to allow the pilot to control the aircraft. Various design philosophies have been proposed and followed to investigate system architectures for these advanced flight control systems. One major area of discussion is whether a multichannel digital control system should be synchronous or asynchronous. This paper addressed the flight experience at the Dryden Flight Research Facility of NASA's Ames Research Center with both synchronous and asynchronous digital flight control systems. Four different flight control systems are evaluated against criteria such as software reliability, cost increases, and schedule delays.
The trend of digital control system design for nuclear power plants in Korea
DOE Office of Scientific and Technical Information (OSTI.GOV)
Park, S. H.; Jung, H. Y.; Yang, C. Y.
2006-07-01
Currently there are 20 nuclear power plants (NPPs) in operation, and 6 more units are under construction in Korea. The control systems of those NPPs have also been developed together with the technology advancement. Control systems started with On-Off control using the relay logic, had been evolved into Solid-State logic using TTL ICs, and applied with the micro-processors since the Yonggwang NPP Units 3 and 4 which started its construction in 1989. Multiplexers are also installed at the local plant areas to collect field input and to send output signals while communicating with the controllers located in the system cabinetsmore » near the main control room in order to reduce the field wiring cables. The design of the digital control system technology for the NPPs in Korea has been optimized to maximize the operability as well as the safety through the design, construction, start-up and operation experiences. Both Shin-Kori Units 1 and 2 and Shin-Wolsong Units 1 and 2 NPP projects under construction are being progressed at the same time. Digital Plant Control Systems of these projects have adopted multi-loop controllers, redundant loop configuration, and soft control system for the radwaste system. Programmable Logic Controller (PLC) and Distributed Control System (DCS) are applied with soft control system in Shin-Kori Units 3 and 4. This paper describes the evolvement of control system at the NPPs in Korea and the experience and design improvement through the observation of the latest failure of the digital control system. In addition, design concept and its trend of the digital control system being applied to the NPP in Korea are introduced. (authors)« less
Development of adaptive control applied to chaotic systems
NASA Astrophysics Data System (ADS)
Rhode, Martin Andreas
1997-12-01
Continuous-time derivative control and adaptive map-based recursive feedback control techniques are used to control chaos in a variety of systems and in situations that are of practical interest. The theoretical part of the research includes the review of fundamental concept of control theory in the context of its applications to deterministic chaotic systems, the development of a new adaptive algorithm to identify the linear system properties necessary for control, and the extension of the recursive proportional feedback control technique, RPF, to high dimensional systems. Chaos control was applied to models of a thermal pulsed combustor, electro-chemical dissolution and the hyperchaotic Rossler system. Important implications for combustion engineering were suggested by successful control of the model of the thermal pulsed combustor. The system was automatically tracked while maintaining control into regions of parameter and state space where no stable attractors exist. In a simulation of the electrochemical dissolution system, application of derivative control to stabilize a steady state, and adaptive RPF to stabilize a period one orbit, was demonstrated. The high dimensional adaptive control algorithm was applied in a simulation using the Rossler hyperchaotic system, where a period-two orbit with two unstable directions was stabilized and tracked over a wide range of a system parameter. In the experimental part, the electrochemical system was studied in parameter space, by scanning the applied potential and the frequency of the rotating copper disk. The automated control algorithm is demonstrated to be effective when applied to stabilize a period-one orbit in the experiment. We show the necessity of small random perturbations applied to the system in order to both learn the dynamics and control the system at the same time. The simultaneous learning and control capability is shown to be an important part of the active feedback control.
14 CFR 25.685 - Control system details.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Control system details. 25.685 Section 25... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Control Systems § 25.685 Control system details. (a) Each detail of each control system must be designed and installed to prevent jamming...
14 CFR 25.685 - Control system details.
Code of Federal Regulations, 2014 CFR
2014-01-01
... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Control Systems § 25.685 Control system details. (a) Each detail of each control system must be designed and installed to prevent jamming... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Control system details. 25.685 Section 25...
14 CFR 25.685 - Control system details.
Code of Federal Regulations, 2011 CFR
2011-01-01
... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Control Systems § 25.685 Control system details. (a) Each detail of each control system must be designed and installed to prevent jamming... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Control system details. 25.685 Section 25...
14 CFR 25.685 - Control system details.
Code of Federal Regulations, 2010 CFR
2010-01-01
... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Control Systems § 25.685 Control system details. (a) Each detail of each control system must be designed and installed to prevent jamming... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Control system details. 25.685 Section 25...
14 CFR 25.685 - Control system details.
Code of Federal Regulations, 2012 CFR
2012-01-01
... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Control Systems § 25.685 Control system details. (a) Each detail of each control system must be designed and installed to prevent jamming... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Control system details. 25.685 Section 25...
14 CFR 27.685 - Control system details.
Code of Federal Regulations, 2013 CFR
2013-01-01
... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Control Systems § 27.685 Control system details. (a) Each detail of each control system must be designed to prevent jamming, chafing, and... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Control system details. 27.685 Section 27...
14 CFR 29.685 - Control system details.
Code of Federal Regulations, 2013 CFR
2013-01-01
... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Control Systems § 29.685 Control system details. (a) Each detail of each control system must be designed to prevent jamming, chafing, and... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Control system details. 29.685 Section 29...
The study on servo-control system in the large aperture telescope
NASA Astrophysics Data System (ADS)
Hu, Wei; Zhenchao, Zhang; Daxing, Wang
2008-08-01
Large astronomical telescope or extremely enormous astronomical telescope servo tracking technique will be one of crucial technology that must be solved in researching and manufacturing. To control technique feature of large astronomical telescope or extremely enormous astronomical telescope, this paper design a sort of large astronomical telescope servo tracking control system. This system composes a principal and subordinate distributed control system, host computer sends steering instruction and receive slave computer functional mode, slave computer accomplish control algorithm and execute real-time control. Large astronomical telescope servo control use direct drive machine, and adopt DSP technology to complete direct torque control algorithm, Such design can not only increase control system performance, but also greatly reduced volume and costs of control system, which has a significant occurrence. The system design scheme can be proved reasonably by calculating and simulating. This system can be applied to large astronomical telescope.
Naval Open Architecture Machinery Control Systems for Next Generation Integrated Power Systems
2012-05-01
PORTABLE) OS / RTOS ADAPTATION MIDDLEWARE (FOR OS PORTABILITY) MACHINERY CONTROLLER FRAMEWORK MACHINERY CONTROL SYSTEM SERVICES POWER CONTROL SYSTEM...SERVICES SHIP SYSTEM SERVICES TTY 0 TTY N … OPERATING SYSTEM ( OS / RTOS ) COMPUTER HARDWARE UDP IP TCP RAW DEV 0 DEV N … POWER MANAGEMENT CONTROLLER...operating systems (DOS, Windows, Linux, OS /2, QNX, SCO Unix ...) COMPUTERS: ISA compatible motherboards, workstations and portables (Compaq, Dell
Biologically inspired rate control of chaos.
Olde Scheper, Tjeerd V
2017-10-01
The overall intention of chaotic control is to eliminate chaos and to force the system to become stable in the classical sense. In this paper, I demonstrate a more subtle method that does not eliminate all traces of chaotic behaviour; yet it consistently, and reliably, can provide control as intended. The Rate Control of Chaos (RCC) method is derived from metabolic control processes and has several remarkable properties. RCC can control complex systems continuously, and unsupervised, it can also maintain control across bifurcations, and in the presence of significant systemic noise. Specifically, I show that RCC can control a typical set of chaotic models, including the 3 and 4 dimensional chaotic Lorenz systems, in all modes. Furthermore, it is capable of controlling spatiotemporal chaos without supervision and maintains control of the system across bifurcations. This property of RCC allows a dynamic system to operate in parameter spaces that are difficult to control otherwise. This may be particularly interesting for the control of forced systems or dynamic systems that are chaotically perturbed. These control properties of RCC are applicable to a range of dynamic systems, thereby appearing to have far-reaching effects beyond just controlling chaos. RCC may also point to the existence of a biochemical control function of an enzyme, to stabilise the dynamics of the reaction cascade.
About development of automation control systems
NASA Astrophysics Data System (ADS)
Myshlyaev, L. P.; Wenger, K. G.; Ivushkin, K. A.; Makarov, V. N.
2018-05-01
The shortcomings of approaches to the development of modern control automation systems and ways of their improvement are given: the correct formation of objects for study and optimization; a joint synthesis of control objects and control systems, an increase in the structural diversity of the elements of control systems. Diagrams of control systems with purposefully variable structure of their elements are presented. Structures of control algorithms for an object with a purposefully variable structure are given.
Control and modeling of a CELSS (Controlled Ecological Life Support System)
NASA Technical Reports Server (NTRS)
Auslander, D. M.; Spear, R. C.; Babcock, P. S.; Nadel, M.
1983-01-01
Research topics that arise from the conceptualization of control for closed life support systems which are life support systems in which all or most of the mass is recycled are discussed. Modeling and control of uncertain and poorly defined systems, resource allocation in closed life support systems, and control structures or systems with delay and closure are emphasized.
Substantiation of the Necessity for Design of Geohod Control System
NASA Astrophysics Data System (ADS)
Aksenov, Vladimir; Chicherin, Ivan; Kostinez, Irina; Kazantsev, Anton; Efremenkov, Andrey
2017-11-01
The article proves the necessity of creatinga control system for the geohod. The scope of application of the geohod is described. The general scheme of the geohod with the main structural elements - cutter drum, head and tail sections, external mover - is described. Enlarged tasks that need to be addressed when creating a control system for the geohod are identified. The tasks of motion control of the geohod in the geomedium, improving the efficiency of the geohod, positioning the geohod in space, control of the support systems, diagnostics of the condition of the geohod, interaction of the control system with the operator are described. The directions of further Zresearch are identified: to formulate the requirements for the geohod control system; to analyze tasks solved by the geohod control system; develop the structure, mathematical models and algorithms for the operation of subsystems of the geohod control system; to develop software to simulate the interaction of subsystems of the geohod control system with each other, with the geomedium and the operator.
Energy Systems Integration News | Energy Systems Integration Facility |
hierarchical control architecture that enables a hybrid control approach, where centralized control systems will be complemented by distributed control algorithms for solar inverters and autonomous control of ), involves developing a novel control scheme that provides system-wide monitoring and control using a small
Indirect learning control for nonlinear dynamical systems
NASA Technical Reports Server (NTRS)
Ryu, Yeong Soon; Longman, Richard W.
1993-01-01
In a previous paper, learning control algorithms were developed based on adaptive control ideas for linear time variant systems. The learning control methods were shown to have certain advantages over their adaptive control counterparts, such as the ability to produce zero tracking error in time varying systems, and the ability to eliminate repetitive disturbances. In recent years, certain adaptive control algorithms have been developed for multi-body dynamic systems such as robots, with global guaranteed convergence to zero tracking error for the nonlinear system euations. In this paper we study the relationship between such adaptive control methods designed for this specific class of nonlinear systems, and the learning control problem for such systems, seeking to converge to zero tracking error in following a specific command repeatedly, starting from the same initial conditions each time. The extension of these methods from the adaptive control problem to the learning control problem is seen to be trivial. The advantages and disadvantages of using learning control based on such adaptive control concepts for nonlinear systems, and the use of other currently available learning control algorithms are discussed.
Communication Needs Assessment for Distributed Turbine Engine Control
NASA Technical Reports Server (NTRS)
Culley, Dennis E.; Behbahani, Alireza R.
2008-01-01
Control system architecture is a major contributor to future propulsion engine performance enhancement and life cycle cost reduction. The control system architecture can be a means to effect net weight reduction in future engine systems, provide a streamlined approach to system design and implementation, and enable new opportunities for performance optimization and increased awareness about system health. The transition from a centralized, point-to-point analog control topology to a modular, networked, distributed system is paramount to extracting these system improvements. However, distributed engine control systems are only possible through the successful design and implementation of a suitable communication system. In a networked system, understanding the data flow between control elements is a fundamental requirement for specifying the communication architecture which, itself, is dependent on the functional capability of electronics in the engine environment. This paper presents an assessment of the communication needs for distributed control using strawman designs and relates how system design decisions relate to overall goals as we progress from the baseline centralized architecture, through partially distributed and fully distributed control systems.
NASA Astrophysics Data System (ADS)
Herbuś, K.; Ociepka, P.
2017-08-01
In the work is analysed a sequential control system of a machine for separating and grouping work pieces for processing. Whereas, the area of the considered problem is related with verification of operation of an actuator system of an electro-pneumatic control system equipped with a PLC controller. Wherein to verification is subjected the way of operation of actuators in view of logic relationships assumed in the control system. The actuators of the considered control system were three drives of linear motion (pneumatic cylinders). And the logical structure of the system of operation of the control system is based on the signals flow graph. The tested logical structure of operation of the electro-pneumatic control system was implemented in the Automation Studio software of B&R company. This software is used to create programs for the PLC controllers. Next, in the FluidSIM software was created the model of the actuator system of the control system of a machine. To verify the created program for the PLC controller, simulating the operation of the created model, it was utilized the approach of integration these two programs using the tool for data exchange in the form of the OPC server.
Software control and system configuration management - A process that works
NASA Technical Reports Server (NTRS)
Petersen, K. L.; Flores, C., Jr.
1983-01-01
A comprehensive software control and system configuration management process for flight-crucial digital control systems of advanced aircraft has been developed and refined to insure efficient flight system development and safe flight operations. Because of the highly complex interactions among the hardware, software, and system elements of state-of-the-art digital flight control system designs, a systems-wide approach to configuration control and management has been used. Specific procedures are implemented to govern discrepancy reporting and reconciliation, software and hardware change control, systems verification and validation testing, and formal documentation requirements. An active and knowledgeable configuration control board reviews and approves all flight system configuration modifications and revalidation tests. This flexible process has proved effective during the development and flight testing of several research aircraft and remotely piloted research vehicles with digital flight control systems that ranged from relatively simple to highly complex, integrated mechanizations.
Framework and Method for Controlling a Robotic System Using a Distributed Computer Network
NASA Technical Reports Server (NTRS)
Sanders, Adam M. (Inventor); Strawser, Philip A. (Inventor); Barajas, Leandro G. (Inventor); Permenter, Frank Noble (Inventor)
2015-01-01
A robotic system for performing an autonomous task includes a humanoid robot having a plurality of compliant robotic joints, actuators, and other integrated system devices that are controllable in response to control data from various control points, and having sensors for measuring feedback data at the control points. The system includes a multi-level distributed control framework (DCF) for controlling the integrated system components over multiple high-speed communication networks. The DCF has a plurality of first controllers each embedded in a respective one of the integrated system components, e.g., the robotic joints, a second controller coordinating the components via the first controllers, and a third controller for transmitting a signal commanding performance of the autonomous task to the second controller. The DCF virtually centralizes all of the control data and the feedback data in a single location to facilitate control of the robot across the multiple communication networks.
Microgrid Controls | Grid Modernization | NREL
Systems Integration Facility. Microgrid Controller Interaction with Distribution Management Systems This project investigates the interaction of distribution management systems with local controllers, including microgrid controllers. The project is developing integrated control and management systems for distribution
Federal Register 2010, 2011, 2012, 2013, 2014
2011-02-17
... for transport category airplanes. These design features include an electronic flight control system... Design Features The GVI has an electronic flight control system and no direct coupling from the cockpit...: Gulfstream Model GVI Airplane; Electronic Flight Control System: Control Surface Position Awareness AGENCY...
NASA Technical Reports Server (NTRS)
Kimball, G., Jr.
1980-01-01
A simulator comparison of the velocity vector control wheel steering (VCWS) system and a decoupled longitudinal control system is presented. The piloting task was to use the electronic attitude direction indicator (EADI) to capture and maintain a 3 degree glide slope in the presence of wind shear and to complete the landing using the perspective runway included on the EADI. The decoupled control system used constant prefilter and feedback gains to provide steady state decoupling of flight path angle, pitch angle, and forward velocity. The decoupled control system improved the pilots' ability to control airspeed and flight path angle during the final stages of an approach made in severe wind shear. The system also improved their ability to complete safe landings. The pilots preferred the decoupled control system in severe winds and, on a pilot rating scale, rated the approach and landing task with the decoupled control system as much as 3 to 4 increments better than use of the VCWS system.
NASA Technical Reports Server (NTRS)
1974-01-01
The transient and steady state response of the respiratory control system for variations in volumetric fractions of inspired gases and special system parameters are modeled. The program contains the capability to change workload. The program is based on Grodins' respiratory control model and can be envisioned as a feedback control system comprised of a plant (the controlled system) and the regulating component (controlling system). The controlled system is partitioned into 3 compartments corresponding to lungs, brain, and tissue with a fluid interconnecting patch representing the blood.
Passivity-Based Control for Two-Wheeled Robot Stabilization
NASA Astrophysics Data System (ADS)
Uddin, Nur; Aryo Nugroho, Teguh; Agung Pramudito, Wahyu
2018-04-01
A passivity-based control system design for two-wheeled robot (TWR) stabilization is presented. A TWR is a statically-unstable non-linear system. A control system is applied to actively stabilize the TWR. Passivity-based control method is applied to design the control system. The design results in a state feedback control law that makes the TWR closed loop system globally asymptotically stable (GAS). The GAS is proven mathematically. The TWR stabilization is demonstrated through computer simulation. The simulation results show that the designed control system is able to stabilize the TWR.
A robust and stable PLC based control system for 40kJ/25kV EMM system
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sharma, Vijay; Saroj, P.C.; Kulkarni, M.R.
2014-07-01
This paper describes the PLC based control system developed for a 40kJ/25kV Electro-magnetic machining (EMM) system. In EMM system large capacitor banks is charged with high voltage to store large energy and the banks is made to discharge into a coil within few milli-seconds using a triggered spark gaps. During discharge of the capacitor large surges and transients are generated in the system. The control system monitors/controls and interlocks all the units of the system for proper operation. The control system is the only subsystem which is electrically connected to all the low and high voltage subsystems. Care should bemore » taken at the signal interfacing with the control system to protect the control system. (author)« less
Application of Calspan pitch rate control system to the Space Shuttle for approach and landing
NASA Technical Reports Server (NTRS)
Weingarten, N. C.; Chalk, C. R.
1983-01-01
A pitch rate control system designed for use in the shuttle during approach and landing was analyzed and compared with a revised control system developed by NASA and the existing OFT control system. The design concept control system uses filtered pitch rate feedback with proportional plus integral paths in the forward loop. Control system parameters were designed as a function of flight configuration. Analysis included time and frequency domain techniques. Results indicate that both the Calspan and NASA systems significantly improve the flying qualities of the shuttle over the OFT. Better attitude and flight path control and less time delay are the primary reasons. The Calspan system is preferred because of reduced time delay and simpler mechanization. Further testing of the improved flight control systems in an in-flight simulator is recommended.
Prototype space station automation system delivered and demonstrated at NASA
NASA Technical Reports Server (NTRS)
Block, Roger F.
1987-01-01
The Automated Subsystem Control for Life Support System (ASCLSS) program has successfully developed and demonstrated a generic approach to the automation and control of Space Station subsystems. The hierarchical and distributed real time controls system places the required controls authority at every level of the automation system architecture. As a demonstration of the automation technique, the ASCLSS system automated the Air Revitalization Group (ARG) of the Space Station regenerative Environmental Control and Life Support System (ECLSS) using real-time, high fidelity simulators of the ARG processess. This automation system represents an early flight prototype and an important test bed for evaluating Space Station controls technology including future application of ADA software in real-time control and the development and demonstration of embedded artificial intelligence and expert systems (AI/ES) in distributed automation and controls systems.
Quantitative safety assessment of air traffic control systems through system control capacity
NASA Astrophysics Data System (ADS)
Guo, Jingjing
Quantitative Safety Assessments (QSA) are essential to safety benefit verification and regulations of developmental changes in safety critical systems like the Air Traffic Control (ATC) systems. Effectiveness of the assessments is particularly desirable today in the safe implementations of revolutionary ATC overhauls like NextGen and SESAR. QSA of ATC systems are however challenged by system complexity and lack of accident data. Extending from the idea "safety is a control problem" in the literature, this research proposes to assess system safety from the control perspective, through quantifying a system's "control capacity". A system's safety performance correlates to this "control capacity" in the control of "safety critical processes". To examine this idea in QSA of the ATC systems, a Control-capacity Based Safety Assessment Framework (CBSAF) is developed which includes two control capacity metrics and a procedural method. The two metrics are Probabilistic System Control-capacity (PSC) and Temporal System Control-capacity (TSC); each addresses an aspect of a system's control capacity. And the procedural method consists three general stages: I) identification of safety critical processes, II) development of system control models and III) evaluation of system control capacity. The CBSAF was tested in two case studies. The first one assesses an en-route collision avoidance scenario and compares three hypothetical configurations. The CBSAF was able to capture the uncoordinated behavior between two means of control, as was observed in a historic midair collision accident. The second case study compares CBSAF with an existing risk based QSA method in assessing the safety benefits of introducing a runway incursion alert system. Similar conclusions are reached between the two methods, while the CBSAF has the advantage of simplicity and provides a new control-based perspective and interpretation to the assessments. The case studies are intended to investigate the potential and demonstrate the utilities of CBSAF and are not intended for thorough studies of collision avoidance and runway incursions safety, which are extremely challenging problems. Further development and thorough validations are required to allow CBSAF to reach implementation phases, e.g. addressing the issues of limited scalability and subjectivity.
Electronic firing systems and methods for firing a device
Frickey, Steven J [Boise, ID; Svoboda, John M [Idaho Falls, ID
2012-04-24
An electronic firing system comprising a control system, a charging system, an electrical energy storage device, a shock tube firing circuit, a shock tube connector, a blasting cap firing circuit, and a blasting cap connector. The control system controls the charging system, which charges the electrical energy storage device. The control system also controls the shock tube firing circuit and the blasting cap firing circuit. When desired, the control system signals the shock tube firing circuit or blasting cap firing circuit to electrically connect the electrical energy storage device to the shock tube connector or the blasting cap connector respectively.
Control and protection system for paralleled modular static inverter-converter systems
NASA Technical Reports Server (NTRS)
Birchenough, A. G.; Gourash, F.
1973-01-01
A control and protection system was developed for use with a paralleled 2.5-kWe-per-module static inverter-converter system. The control and protection system senses internal and external fault parameters such as voltage, frequency, current, and paralleling current unbalance. A logic system controls contactors to isolate defective power conditioners or loads. The system sequences contactor operation to automatically control parallel operation, startup, and fault isolation. Transient overload protection and fault checking sequences are included. The operation and performance of a control and protection system, with detailed circuit descriptions, are presented.
46 CFR 62.25-10 - Manual alternate control systems.
Code of Federal Regulations, 2011 CFR
2011-10-01
... automatic primary control system failure; (2) Be suitable for manual control for prolonged periods; (3) Be... 46 Shipping 2 2011-10-01 2011-10-01 false Manual alternate control systems. 62.25-10 Section 62.25... AUTOMATION General Requirements for All Automated Vital Systems § 62.25-10 Manual alternate control systems...
14 CFR 29.679 - Control system locks.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Control system locks. 29.679 Section 29.679... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Control Systems § 29.679 Control system locks. If there is a device to lock the control system with the rotorcraft on the ground or water, there...
14 CFR 27.679 - Control system locks.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Control system locks. 27.679 Section 27.679... STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Control Systems § 27.679 Control system locks. If there is a device to lock the control system with the rotorcraft on the ground or water, there...
49 CFR 193.2619 - Control systems.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 49 Transportation 3 2013-10-01 2013-10-01 false Control systems. 193.2619 Section 193.2619...: FEDERAL SAFETY STANDARDS Maintenance § 193.2619 Control systems. (a) Each control system must be properly adjusted to operate within design limits. (b) If a control system is out of service for 30 days or more, it...
49 CFR 193.2619 - Control systems.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 49 Transportation 3 2011-10-01 2011-10-01 false Control systems. 193.2619 Section 193.2619...: FEDERAL SAFETY STANDARDS Maintenance § 193.2619 Control systems. (a) Each control system must be properly adjusted to operate within design limits. (b) If a control system is out of service for 30 days or more, it...
49 CFR 193.2619 - Control systems.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 3 2010-10-01 2010-10-01 false Control systems. 193.2619 Section 193.2619...: FEDERAL SAFETY STANDARDS Maintenance § 193.2619 Control systems. (a) Each control system must be properly adjusted to operate within design limits. (b) If a control system is out of service for 30 days or more, it...
49 CFR 193.2619 - Control systems.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 49 Transportation 3 2012-10-01 2012-10-01 false Control systems. 193.2619 Section 193.2619...: FEDERAL SAFETY STANDARDS Maintenance § 193.2619 Control systems. (a) Each control system must be properly adjusted to operate within design limits. (b) If a control system is out of service for 30 days or more, it...
49 CFR 193.2619 - Control systems.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 49 Transportation 3 2014-10-01 2014-10-01 false Control systems. 193.2619 Section 193.2619...: FEDERAL SAFETY STANDARDS Maintenance § 193.2619 Control systems. (a) Each control system must be properly adjusted to operate within design limits. (b) If a control system is out of service for 30 days or more, it...
14 CFR 27.679 - Control system locks.
Code of Federal Regulations, 2013 CFR
2013-01-01
... STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Control Systems § 27.679 Control system locks. If there is a device to lock the control system with the rotorcraft on the ground or water, there... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Control system locks. 27.679 Section 27.679...
14 CFR 23.679 - Control system locks.
Code of Federal Regulations, 2012 CFR
2012-01-01
... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Design and Construction Control Systems § 23.679 Control system locks. If there is a device to lock the control system on the ground or... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Control system locks. 23.679 Section 23.679...
14 CFR 23.679 - Control system locks.
Code of Federal Regulations, 2011 CFR
2011-01-01
... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Design and Construction Control Systems § 23.679 Control system locks. If there is a device to lock the control system on the ground or... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Control system locks. 23.679 Section 23.679...
14 CFR 23.679 - Control system locks.
Code of Federal Regulations, 2010 CFR
2010-01-01
... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Design and Construction Control Systems § 23.679 Control system locks. If there is a device to lock the control system on the ground or... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Control system locks. 23.679 Section 23.679...
14 CFR 23.679 - Control system locks.
Code of Federal Regulations, 2013 CFR
2013-01-01
... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Design and Construction Control Systems § 23.679 Control system locks. If there is a device to lock the control system on the ground or... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Control system locks. 23.679 Section 23.679...
14 CFR 23.679 - Control system locks.
Code of Federal Regulations, 2014 CFR
2014-01-01
... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Design and Construction Control Systems § 23.679 Control system locks. If there is a device to lock the control system on the ground or... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Control system locks. 23.679 Section 23.679...
14 CFR 29.679 - Control system locks.
Code of Federal Regulations, 2013 CFR
2013-01-01
... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Control Systems § 29.679 Control system locks. If there is a device to lock the control system with the rotorcraft on the ground or water, there... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Control system locks. 29.679 Section 29.679...
Evaluating Multi-Input/Multi-Output Digital Control Systems
NASA Technical Reports Server (NTRS)
Pototzky, Anthony S.; Wieseman, Carol D.; Hoadley, Sherwood T.; Mukhopadhyay, Vivek
1994-01-01
Controller-performance-evaluation (CPE) methodology for multi-input/multi-output (MIMO) digital control systems developed. Procedures identify potentially destabilizing controllers and confirm satisfactory performance of stabilizing ones. Methodology generic and used in many types of multi-loop digital-controller applications, including digital flight-control systems, digitally controlled spacecraft structures, and actively controlled wind-tunnel models. Also applicable to other complex, highly dynamic digital controllers, such as those in high-performance robot systems.
An Improved Method to Control the Critical Parameters of a Multivariable Control System
NASA Astrophysics Data System (ADS)
Subha Hency Jims, P.; Dharmalingam, S.; Wessley, G. Jims John
2017-10-01
The role of control systems is to cope with the process deficiencies and the undesirable effect of the external disturbances. Most of the multivariable processes are highly iterative and complex in nature. Aircraft systems, Modern Power Plants, Refineries, Robotic systems are few such complex systems that involve numerous critical parameters that need to be monitored and controlled. Control of these important parameters is not only tedious and cumbersome but also is crucial from environmental, safety and quality perspective. In this paper, one such multivariable system, namely, a utility boiler has been considered. A modern power plant is a complex arrangement of pipework and machineries with numerous interacting control loops and support systems. In this paper, the calculation of controller parameters based on classical tuning concepts has been presented. The controller parameters thus obtained and employed has controlled the critical parameters of a boiler during fuel switching disturbances. The proposed method can be applied to control the critical parameters like elevator, aileron, rudder, elevator trim rudder and aileron trim, flap control systems of aircraft systems.
Control system for 5 MW neutral beam ion source for SST1
NASA Astrophysics Data System (ADS)
Patel, G. B.; Onali, Raja; Sharma, Vivek; Suresh, S.; Tripathi, V.; Bandyopadhyay, M.; Singh, N. P.; Thakkar, Dipal; Gupta, L. N.; Singh, M. J.; Patel, P. J.; Chakraborty, A. K.; Baruah, U. K.; Mattoo, S. K.
2006-01-01
This article describes the control system for a 5MW ion source of the NBI (neutral beam injector) for steady-state superconducting tokamak-1 (SST-1). The system uses both hardware and software solutions. It comprises a DAS (data acquisition system) and a control system. The DAS is used to read the voltage and current signals from eight filament heater power supplies and 24 discharge power supplies. The control system is used to adjust the filament heater current in order to achieve an effective control on the discharge current in the plasma box. The system consists of a VME (Verse Module Eurocard) system and C application program running on a VxWorks™ real-time operating system. A PID (proportional, integral, and differential) algorithm is used to control the filament heater current. Experiments using this system have shown that the discharge current can be controlled within 1% accuracy for a PID loop time of 20ms. Response of the control system to the pressure variation of the gas in the chamber has also been studied and compared with the results obtained from those of an uncontrolled system. The present approach increases the flexibility of the control system. It not only eases the control of the plasma but also allows an easy changeover to various operation scenarios.
SPring-8 beamline control system.
Ohata, T; Konishi, H; Kimura, H; Furukawa, Y; Tamasaku, K; Nakatani, T; Tanabe, T; Matsumoto, N; Ishii, M; Ishikawa, T
1998-05-01
The SPring-8 beamline control system is now taking part in the control of the insertion device (ID), front end, beam transportation channel and all interlock systems of the beamline: it will supply a highly standardized environment of apparatus control for collaborative researchers. In particular, ID operation is very important in a third-generation synchrotron light source facility. It is also very important to consider the security system because the ID is part of the storage ring and is therefore governed by the synchrotron ring control system. The progress of computer networking systems and the technology of security control require the development of a highly flexible control system. An interlock system that is independent of the control system has increased the reliability. For the beamline control system the so-called standard model concept has been adopted. VME-bus (VME) is used as the front-end control system and a UNIX workstation as the operator console. CPU boards of the VME-bus are RISC processor-based board computers operated by a LynxOS-based HP-RT real-time operating system. The workstation and the VME are linked to each other by a network, and form the distributed system. The HP 9000/700 series with HP-UX and the HP 9000/743rt series with HP-RT are used. All the controllable apparatus may be operated from any workstation.
Management and control of self-replicating systems: A systems model
NASA Technical Reports Server (NTRS)
Vontiesenhausen, G.
1982-01-01
In 1980, a conceptual engineering approach to self-replicating systems was achieved. The design was based on von Newmann's kinematic version of self-replicating automata. The systems management and control and the organization of the control elements are reported. After developing the functional requirements of such a system, a hierarchy of three management and control levels is described. These are an autonomous, an external, and an intelligent management and control system. Systems recycling, systems specialization, and information replication are discussed.
Data-Driven Based Asynchronous Motor Control for Printing Servo Systems
NASA Astrophysics Data System (ADS)
Bian, Min; Guo, Qingyun
Modern digital printing equipment aims to the environmental-friendly industry with high dynamic performances and control precision and low vibration and abrasion. High performance motion control system of printing servo systems was required. Control system of asynchronous motor based on data acquisition was proposed. Iterative learning control (ILC) algorithm was studied. PID control was widely used in the motion control. However, it was sensitive to the disturbances and model parameters variation. The ILC applied the history error data and present control signals to approximate the control signal directly in order to fully track the expect trajectory without the system models and structures. The motor control algorithm based on the ILC and PID was constructed and simulation results were given. The results show that data-driven control method is effective dealing with bounded disturbances for the motion control of printing servo systems.
NASA Astrophysics Data System (ADS)
Eguiraun, M.; Jugo, J.; Arredondo, I.; del Campo, M.; Feuchtwanger, J.; Etxebarria, V.; Bermejo, F. J.
2013-04-01
ISHN (Ion Source Hydrogen Negative) consists of a Penning type ion source in operation at ESS-Bilbao facilities. From the control point of view, this source is representative of the first steps and decisions taken towards the general control architecture of the whole accelerator to be built. The ISHN main control system is based on a PXI architecture, under a real-time controller which is programmed using LabVIEW. This system, with additional elements, is connected to the general control system. The whole system is based on EPICS for the control network, and the modularization of the communication layers of the accelerator plays an important role in the proposed control architecture.
Implementation of EPICS based vacuum control system for variable energy cyclotron centre, Kolkata
DOE Office of Scientific and Technical Information (OSTI.GOV)
Roy, Anindya, E-mail: r-ani@vecc.gov.in; Bhole, R. B.; Nandy, Partha P.
2015-03-15
The vacuum system of the Room Temperature (K = 130) Cyclotron of Variable Energy Cyclotron Centre is comprised of vacuum systems of main machine and Beam Transport System. The vacuum control system is upgraded to a PLC based Automated system from the initial relay based Manual system. The supervisory control of the vacuum system is implemented in Experimental Physics and Industrial Control System (EPICS). An EPICS embedded ARM based vacuum gauge controller is developed to mitigate the requirement of vendor specific gauge controller for gauges and also for seamless integration of the gauge controllers with the control system. A setmore » of MS-Windows ActiveX components with embedded EPICS Channel Access interface are developed to build operator interfaces with less complex programming and to incorporate typical Windows feature, e.g., user authentication, file handling, better fonts, colors, mouse actions etc. into the operator interfaces. The control parameters, monitoring parameters, and system interlocks of the system are archived in MySQL based EPICS MySQL Archiver developed indigenously. In this paper, we describe the architecture, the implementation details, and the performance of the system.« less
NASA Technical Reports Server (NTRS)
Wheatley, Thomas E.; Michaloski, John L.; Lumia, Ronald
1989-01-01
Analysis of a robot control system leads to a broad range of processing requirements. One fundamental requirement of a robot control system is the necessity of a microcomputer system in order to provide sufficient processing capability.The use of multiple processors in a parallel architecture is beneficial for a number of reasons, including better cost performance, modular growth, increased reliability through replication, and flexibility for testing alternate control strategies via different partitioning. A survey of the progression from low level control synchronizing primitives to higher level communication tools is presented. The system communication and control mechanisms of existing robot control systems are compared to the hierarchical control model. The impact of this design methodology on the current robot control systems is explored.
Behaviour of a series of reservoirs separated by drowned gates
NASA Astrophysics Data System (ADS)
Kolechkina, Alla; van Nooijen, Ronald
2017-04-01
Modern control systems tend to be based on computers and therefore to operate by sending commands to structures at given intervals (discrete time control system). Moreover, for almost all water management control systems there are practical lower limits on the time interval between structure adjustments and even between measurements. The water resource systems that are being controlled are physical systems whose state changes continuously. If we combine a continuously changing system and a discrete time controller we get a hybrid system. We use material from recent control theory literature to examine the behaviour of a series of reservoirs separated by drowned gates where the gates are under computer control.
Intrusion Detection in Control Systems using Sequence Characteristics
NASA Astrophysics Data System (ADS)
Kiuchi, Mai; Onoda, Takashi
Intrusion detection is considered effective in control systems. Sequences of the control application behavior observed in the communication, such as the order of the control device to be controlled, are important in control systems. However, most intrusion detection systems do not effectively reflect sequences in the application layer into the detection rules. In our previous work, we considered utilizing sequences for intrusion detection in control systems, and demonstrated the usefulness of sequences for intrusion detection. However, manually writing the detection rules for a large system can be difficult, so using machine learning methods becomes feasible. Also, in the case of control systems, there have been very few observed cyber attacks, so we have very little knowledge of the attack data that should be used to train the intrusion detection system. In this paper, we use an approach that combines CRF (Conditional Random Field) considering the sequence of the system, thus able to reflect the characteristics of control system sequences into the intrusion detection system, and also does not need the knowledge of attack data to construct the detection rules.
49 CFR 235.5 - Changes requiring filing of application.
Code of Federal Regulations, 2010 CFR
2010-10-01
... system, automatic train stop, train control, or cab signal system or other similar appliance or device..., automatic train stop, train control, or cab signal system; or (3) The modification of a block signal system, interlocking, traffic control system, automatic train stop, train control, or cab signal system. (b) [Reserved...
49 CFR 235.5 - Changes requiring filing of application.
Code of Federal Regulations, 2011 CFR
2011-10-01
... system, automatic train stop, train control, or cab signal system or other similar appliance or device..., automatic train stop, train control, or cab signal system; or (3) The modification of a block signal system, interlocking, traffic control system, automatic train stop, train control, or cab signal system. (b) [Reserved...
NASA Technical Reports Server (NTRS)
Belcastro, Celeste M.
1989-01-01
Digital control systems for applications such as aircraft avionics and multibody systems must maintain adequate control integrity in adverse as well as nominal operating conditions. For example, control systems for advanced aircraft, and especially those with relaxed static stability, will be critical to flight and will, therefore, have very high reliability specifications which must be met regardless of operating conditions. In addition, multibody systems such as robotic manipulators performing critical functions must have control systems capable of robust performance in any operating environment in order to complete the assigned task reliably. Severe operating conditions for electronic control systems can result from electromagnetic disturbances caused by lightning, high energy radio frequency (HERF) transmitters, and nuclear electromagnetic pulses (NEMP). For this reason, techniques must be developed to evaluate the integrity of the control system in adverse operating environments. The most difficult and illusive perturbations to computer-based control systems that can be caused by an electromagnetic environment (EME) are functional error modes that involve no component damage. These error modes are collectively known as upset, can occur simultaneously in all of the channels of a redundant control system, and are software dependent. Upset studies performed to date have not addressed the assessment of fault tolerant systems and do not involve the evaluation of a control system operating in a closed-loop with the plant. A methodology for performing a real-time simulation of the closed-loop dynamics of a fault tolerant control system with a simulated plant operating in an electromagnetically harsh environment is presented. In particular, considerations for performing upset tests on the controller are discussed. Some of these considerations are the generation and coupling of analog signals representative of electromagnetic disturbances to a control system under test, analog data acquisition, and digital data acquisition from fault tolerant systems. In addition, a case study of an upset test methodology for a fault tolerant electromagnetic aircraft engine control system is presented.
Dynamic Programming Method for Impulsive Control Problems
ERIC Educational Resources Information Center
Balkew, Teshome Mogessie
2015-01-01
In many control systems changes in the dynamics occur unexpectedly or are applied by a controller as needed. The time at which a controller implements changes is not necessarily known a priori. For example, many manufacturing systems and flight operations have complicated control systems, and changes in the control systems may be automatically…
Interactive Implementation of the Optimal Systems Control Design Program (OPTSYSX) on the IBM 3033.
1984-03-01
DAS A44 159 INTERACTIVE IMPLEMENTATION OF THE OPTIMAL SYSTEMS I CONTROL DESIGN PROGRAM (OPTSYSX) ON THE 1DM 3033(U NAVAL POSTGRADUATE SCHOOL MONTEREY...noesear end idswtif’r b block number) Optimal Systems Control Systems Control Control Systems 10.; ABSTRACT (Continu an reveree side ff Roe684v ad Id yI...34 by block number) .- This thesis discusses the modification of an existing Optimal Systems Control FORTRAN program (OPTSYS) originally obtained from
Propulsion system/flight control integration for supersonic aircraft
NASA Technical Reports Server (NTRS)
Reukauf, P. J.; Burcham, F. W., Jr.
1976-01-01
Digital integrated control systems are studied. Such systems allow minimization of undesirable interactions while maximizing performance at all flight conditions. One such program is the YF-12 cooperative control program. The existing analog air data computer, autothrottle, autopilot, and inlet control systems are converted to digital systems by using a general purpose airborne computer and interface unit. Existing control laws are programed and tested in flight. Integrated control laws, derived using accurate mathematical models of the airplane and propulsion system in conjunction with modern control techniques, are tested in flight. Analysis indicates that an integrated autothrottle autopilot gives good flight path control and that observers are used to replace failed sensors.
Towards A Taxonomy Of Attacks Against Energy Control Systems
NASA Astrophysics Data System (ADS)
Fleury, Terry; Khurana, Himanshu; Welch, Von
Control systems in the energy sector (e.g., supervisory control and data acquisition (SCADA) systems) involve a hierarchy of sensing, monitoring and control devices connected to centralized control stations or centers. The incorporation of commercial off-the-shelf technologies in energy control systems makes them vulnerable to cyber attacks. A taxonomy of cyber attacks against control systems can assist the energy sector in managing the cyber threat. This paper takes the first step towards a taxonomy by presenting a comprehensive model of attacks, vulnerabilities and damage related to control systems. The model is populated based on a survey of the technical literature from industry, academia and national laboratories.
NASA Technical Reports Server (NTRS)
Theodore, Colin R.; Tischler, Mark B.
2010-01-01
An automatic rotor trim control system was developed and successfully used during a wind tunnel test of a full-scale UH-60 rotor system with Individual Blade Control (IBC) actuators. The trim control system allowed rotor trim to be set more quickly, precisely and repeatably than in previous wind tunnel tests. This control system also allowed the rotor trim state to be maintained during transients and drift in wind tunnel flow, and through changes in IBC actuation. The ability to maintain a consistent rotor trim state was key to quickly and accurately evaluating the effect of IBC on rotor performance, vibration, noise and loads. This paper presents details of the design and implementation of the trim control system including the rotor system hardware, trim control requirements, and trim control hardware and software implementation. Results are presented showing the effect of IBC on rotor trim and dynamic response, a validation of the rotor dynamic simulation used to calculate the initial control gains and tuning of the control system, and the overall performance of the trim control system during the wind tunnel test.
Switching Systems: Controllability and Control Design
2009-04-25
controllable linear time invariant (LTI) systems ẋ = Ax+Bu are stabilizable and the stabilization can be always done by a...to control the system is bounded. As an application controllability conditions for a class of bimodal linear time invariant (LTI) systems are also...There exist a universal ( finite ) switching sequence σ such that the time varying system ẋ = A(σ)x+ B(σ)u is globally controllable . Proof: The
Design and development progress of a LLRF control system for a 500 MHz superconducting cavity
NASA Astrophysics Data System (ADS)
Lee, Y. S.; Kim, H. W.; Song, H. S.; Lee, J. H.; Park, K. H.; Yu, I. H.; Chai, J. S.
2012-07-01
The LLRF (low-level radio-frequency) control system which regulates the amplitude and the phase of the accelerating voltage inside a RF cavity is essential to ensure the stable operation of charged particle accelerators. Recent advances in digital signal processors and data acquisition systems have allowed the LLRF control system to be implemented in digitally and have made it possible to meet the higher demands associated with the performance of LLRF control systems, such as stability, accuracy, etc. For this reason, many accelerator laboratories have completed or are completing the developments of digital LLRF control systems. The digital LLRF control system has advantages related with flexibility and fast reconfiguration. This paper describes the design of the FPGA (field programmable gate array) based LLRF control system and the status of development for this system. The proposed LLRF control system includes an analog front-end, a digital board (ADC (analog to digital converter), DAC (digital to analog converter), FPGA, etc.) and a RF & clock generation system. The control algorithms will be implemented by using the VHDL (VHSIC (very high speed integrated circuits) hardware description language), and the EPICS (experiment physics and industrial control system) will be ported to the host computer for the communication. In addition, the purpose of this system is to control a 500 MHz RF cavity, so the system will be applied to the superconducting cavity to be installed in the PLS storage ring, and its performance will be tested.
An intelligent position-specific training system for mission operations
NASA Technical Reports Server (NTRS)
Schneider, M. P.
1992-01-01
Marshall Space Flight Center's (MSFC's) payload ground controller training program provides very good generic training; however, ground controller position-specific training can be improved by including position-specific training systems in the training program. This report explains why MSFC needs to improve payload ground controller position-specific training. The report describes a generic syllabus for position-specific training systems, a range of system designs for position-specific training systems, and a generic development process for developing position-specific training systems. The report also describes a position-specific training system prototype that was developed for the crew interface coordinator payload operations control center ground controller position. The report concludes that MSFC can improve the payload ground controller training program by incorporating position-specific training systems for each ground controller position; however, MSFC should not develop position-specific training systems unless payload ground controller position experts will be available to participate in the development process.
Development of monitoring and control system for a mine main fan based on frequency converter
NASA Astrophysics Data System (ADS)
Zhang, Y. C.; Zhang, R. W.; Kong, X. Z.; Y Gong, J.; Chen, Q. G.
2013-12-01
In the process of mine exploitation, the requirement of air flow rate often changes. The procedure of traditional control mode of the fan is complex and it is hard to meet the worksite requirement for air. This system is based on Principal Computer (PC) monitoring system and high performance PLC control system. In this system, the frequency converter is adapted to adjust the fan speed and the air of worksite can be regulated steplessly. The function of the monitoring and control system contains on-line monitoring and centralized control. The system can monitor the parameters of fan in real-time, control the operation of frequency converter, as well as, control the fan and its accessory equipments. At the same time, the automation level of the system is highly, the field equipments can be monitored and controlled automatically. So, the system is an important safeguard for mine production.
Nuclear electric propulsion reactor control systems status
NASA Technical Reports Server (NTRS)
Ferg, D. A.
1973-01-01
The thermionic reactor control system design studies conducted over the past several years for a nuclear electric propulsion system are described and summarized. The relevant reactor control system studies are discussed in qualitative terms, pointing out the significant advantages and disadvantages including the impact that the various control systems would have on the nuclear electric propulsion system design. A recommendation for the reference control system is made, and a program for future work leading to an engineering model is described.
Muniraj, Murali; Arulmozhiyal, Ramaswamy
2015-01-01
A control actuation system has been used extensively in automotive, aerospace, and defense applications. The major challenges in modeling control actuation system are rise time, maximum peak to peak overshoot, and response to nonlinear system with percentage error. This paper addresses the challenges in modeling and real time implementation of control actuation system for missiles glider applications. As an alternative fuzzy-PID controller is proposed in BLDC motor drive followed by linkage mechanism to actuate fins in missiles and gliders. The proposed system will realize better rise time and less overshoot while operating in extreme nonlinear dynamic system conditions. A mathematical model of BLDC motor is derived in state space form. The complete control actuation system is modeled in MATLAB/Simulink environment and verified by performing simulation studies. A real time prototype of the control actuation is developed with dSPACE-1104 hardware controller and a detailed analysis is carried out to confirm the viability of the proposed system. PMID:26613102
Muniraj, Murali; Arulmozhiyal, Ramaswamy
2015-01-01
A control actuation system has been used extensively in automotive, aerospace, and defense applications. The major challenges in modeling control actuation system are rise time, maximum peak to peak overshoot, and response to nonlinear system with percentage error. This paper addresses the challenges in modeling and real time implementation of control actuation system for missiles glider applications. As an alternative fuzzy-PID controller is proposed in BLDC motor drive followed by linkage mechanism to actuate fins in missiles and gliders. The proposed system will realize better rise time and less overshoot while operating in extreme nonlinear dynamic system conditions. A mathematical model of BLDC motor is derived in state space form. The complete control actuation system is modeled in MATLAB/Simulink environment and verified by performing simulation studies. A real time prototype of the control actuation is developed with dSPACE-1104 hardware controller and a detailed analysis is carried out to confirm the viability of the proposed system.
NASA Technical Reports Server (NTRS)
1982-01-01
The active control technology (ACT) control/guidance system task of the integrated application of active controls (IAAC) technology project within the NASA energy efficient transport program was documented. The air traffic environment of navigation and air traffic control systems and procedures were extrapolated. An approach to listing flight functions which will be performed by systems and crew of an ACT configured airplane of the 1990s, and a determination of function criticalities to safety of flight, are the basis of candidate integrated ACT/Control/Guidance System architecture. The system mechanizes five active control functions: pitch augmented stability, angle of attack limiting, lateral/directional augmented stability, gust load alleviation, and maneuver load control. The scope and requirements of a program for simulating the integrated ACT avionics and flight deck system, with pilot in the loop, are defined, system and crew interface elements are simulated, and mechanization is recommended. Relationships between system design and crew roles and procedures are evaluated.
Automated Subsystem Control for Life Support System (ASCLSS)
NASA Technical Reports Server (NTRS)
Block, Roger F.
1987-01-01
The Automated Subsystem Control for Life Support Systems (ASCLSS) program has successfully developed and demonstrated a generic approach to the automation and control of space station subsystems. The automation system features a hierarchical and distributed real-time control architecture which places maximum controls authority at the lowest or process control level which enhances system autonomy. The ASCLSS demonstration system pioneered many automation and control concepts currently being considered in the space station data management system (DMS). Heavy emphasis is placed on controls hardware and software commonality implemented in accepted standards. The approach demonstrates successfully the application of real-time process and accountability with the subsystem or process developer. The ASCLSS system completely automates a space station subsystem (air revitalization group of the ASCLSS) which moves the crew/operator into a role of supervisory control authority. The ASCLSS program developed over 50 lessons learned which will aide future space station developers in the area of automation and controls..
NASA Technical Reports Server (NTRS)
Zeigler, Bernard P.
1989-01-01
It is shown how systems can be advantageously represented as discrete-event models by using DEVS (discrete-event system specification), a set-theoretic formalism. Such DEVS models provide a basis for the design of event-based logic control. In this control paradigm, the controller expects to receive confirming sensor responses to its control commands within definite time windows determined by its DEVS model of the system under control. The event-based contral paradigm is applied in advanced robotic and intelligent automation, showing how classical process control can be readily interfaced with rule-based symbolic reasoning systems.
Control of a solar-energy-supplied electrical-power system without intermediate circuitry
NASA Astrophysics Data System (ADS)
Leistner, K.
A computer control system is developed for electric-power systems comprising solar cells and small numbers of users with individual centrally controlled converters (and storage facilities when needed). Typical system structures are reviewed; the advantages of systems without an intermediate network are outlined; the demands on a control system in such a network (optimizing generator working point and power distribution) are defined; and a flexible modular prototype system is described in detail. A charging station for lead batteries used in electric automobiles is analyzed as an example. The power requirements of the control system (30 W for generator control and 50 W for communications and distribution control) are found to limit its use to larger networks.
14 CFR 25.1161 - Fuel jettisoning system controls.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Fuel jettisoning system controls. 25.1161... AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Powerplant Controls and Accessories § 25.1161 Fuel jettisoning system controls. Each fuel jettisoning system control must have guards...
14 CFR 25.1161 - Fuel jettisoning system controls.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Fuel jettisoning system controls. 25.1161... AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Powerplant Controls and Accessories § 25.1161 Fuel jettisoning system controls. Each fuel jettisoning system control must have guards...
14 CFR 25.1161 - Fuel jettisoning system controls.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Fuel jettisoning system controls. 25.1161... AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Powerplant Controls and Accessories § 25.1161 Fuel jettisoning system controls. Each fuel jettisoning system control must have guards...
14 CFR 25.1161 - Fuel jettisoning system controls.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Fuel jettisoning system controls. 25.1161... AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Powerplant Controls and Accessories § 25.1161 Fuel jettisoning system controls. Each fuel jettisoning system control must have guards...
14 CFR 25.1161 - Fuel jettisoning system controls.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Fuel jettisoning system controls. 25.1161... AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Powerplant Controls and Accessories § 25.1161 Fuel jettisoning system controls. Each fuel jettisoning system control must have guards...
Controllability of discrete bilinear systems with bounded control.
NASA Technical Reports Server (NTRS)
Tarn, T. J.; Elliott, D. L.; Goka, T.
1973-01-01
The subject of this paper is the controllability of time-invariant discrete-time bilinear systems. Bilinear systems are classified into two categories; homogeneous and inhomogeneous. Sufficient conditions which ensure the global controllability of discrete-time bilinear systems are obtained by localized analysis in control variables.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhao, Y.; Edwards, R.M.; Lee, K.Y.
1997-03-01
In this paper, a simplified model with a lower order is first developed for a nuclear steam generator system and verified against some realistic environments. Based on this simplified model, a hybrid multi-input and multi-out (MIMO) control system, consisting of feedforward control (FFC) and feedback control (FBC), is designed for wide range conditions by using the genetic algorithm (GA) technique. The FFC control, obtained by the GA optimization method, injects an a priori command input into the system to achieve an optimal performance for the designed system, while the GA-based FBC control provides the necessary compensation for any disturbances ormore » uncertainties in a real steam generator. The FBC control is an optimal design of a PI-based control system which would be more acceptable for industrial practices and power plant control system upgrades. The designed hybrid MIMO FFC/FBC control system is first applied to the simplified model and then to a more complicated model with a higher order which is used as a substitute of the real system to test the efficacy of the designed control system. Results from computer simulations show that the designed GA-based hybrid MIMO FFC/FBC control can achieve good responses and robust performances. Hence, it can be considered as a viable alternative to the current control system upgrade.« less
NASA Technical Reports Server (NTRS)
Beach, R. F.; Kimnach, G. L.; Jett, T. A.; Trash, L. M.
1989-01-01
The Lewis Research Center's Power Management and Distribution (PMAD) System testbed and its use in the evaluation of control concepts applicable to the NASA Space Station Freedom electric power system (EPS) are described. The facility was constructed to allow testing of control hardware and software in an environment functionally similar to the space station electric power system. Control hardware and software have been developed to allow operation of the testbed power system in a manner similar to a supervisory control and data acquisition (SCADA) system employed by utility power systems for control. The system hardware and software are described.
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.
An Evaluation of Automatic Control System Concepts for General Aviation Airplanes
NASA Technical Reports Server (NTRS)
Stewart, E. C.
1990-01-01
A piloted simulation study of automatic longitudinal control systems for general aviation airplanes has been conducted. These automatic control systems were designed to make the simulated airplane easy to fly for a beginning or infrequent pilot. Different control systems are presented and their characteristics are documented. In a conventional airplane control system each cockpit controller commands combinations of both the airspeed and the vertical speed. The best system in the present study decoupled the airspeed and vertical speed responses to cockpit controller inputs. An important feature of the automatic system was that neither changing flap position nor maneuvering in steeply banked turns affected either the airspeed or the vertical speed. All the pilots who flew the control system simulation were favorably impressed with the very low workload and the excellent handling qualities of the simulated airplane.
Method study on fuzzy-PID adaptive control of electric-hydraulic hitch system
NASA Astrophysics Data System (ADS)
Li, Mingsheng; Wang, Liubu; Liu, Jian; Ye, Jin
2017-03-01
In this paper, fuzzy-PID adaptive control method is applied to the control of tractor electric-hydraulic hitch system. According to the characteristics of the system, a fuzzy-PID adaptive controller is designed and the electric-hydraulic hitch system model is established. Traction control and position control performance simulation are carried out with the common PID control method. A field test rig was set up to test the electric-hydraulic hitch system. The test results showed that, after the fuzzy-PID adaptive control is adopted, when the tillage depth steps from 0.1m to 0.3m, the system transition process time is 4s, without overshoot, and when the tractive force steps from 3000N to 7000N, the system transition process time is 5s, the system overshoot is 25%.
Control algorithms and applications of the wavefront sensorless adaptive optics
NASA Astrophysics Data System (ADS)
Ma, Liang; Wang, Bin; Zhou, Yuanshen; Yang, Huizhen
2017-10-01
Compared with the conventional adaptive optics (AO) system, the wavefront sensorless (WFSless) AO system need not to measure the wavefront and reconstruct it. It is simpler than the conventional AO in system architecture and can be applied to the complex conditions. Based on the analysis of principle and system model of the WFSless AO system, wavefront correction methods of the WFSless AO system were divided into two categories: model-free-based and model-based control algorithms. The WFSless AO system based on model-free-based control algorithms commonly considers the performance metric as a function of the control parameters and then uses certain control algorithm to improve the performance metric. The model-based control algorithms include modal control algorithms, nonlinear control algorithms and control algorithms based on geometrical optics. Based on the brief description of above typical control algorithms, hybrid methods combining the model-free-based control algorithm with the model-based control algorithm were generalized. Additionally, characteristics of various control algorithms were compared and analyzed. We also discussed the extensive applications of WFSless AO system in free space optical communication (FSO), retinal imaging in the human eye, confocal microscope, coherent beam combination (CBC) techniques and extended objects.
Prediction of epigenetically regulated genes in breast cancer cell lines.
Loss, Leandro A; Sadanandam, Anguraj; Durinck, Steffen; Nautiyal, Shivani; Flaucher, Diane; Carlton, Victoria E H; Moorhead, Martin; Lu, Yontao; Gray, Joe W; Faham, Malek; Spellman, Paul; Parvin, Bahram
2010-06-04
Methylation of CpG islands within the DNA promoter regions is one mechanism that leads to aberrant gene expression in cancer. In particular, the abnormal methylation of CpG islands may silence associated genes. Therefore, using high-throughput microarrays to measure CpG island methylation will lead to better understanding of tumor pathobiology and progression, while revealing potentially new biomarkers. We have examined a recently developed high-throughput technology for measuring genome-wide methylation patterns called mTACL. Here, we propose a computational pipeline for integrating gene expression and CpG island methylation profiles to identify epigenetically regulated genes for a panel of 45 breast cancer cell lines, which is widely used in the Integrative Cancer Biology Program (ICBP). The pipeline (i) reduces the dimensionality of the methylation data, (ii) associates the reduced methylation data with gene expression data, and (iii) ranks methylation-expression associations according to their epigenetic regulation. Dimensionality reduction is performed in two steps: (i) methylation sites are grouped across the genome to identify regions of interest, and (ii) methylation profiles are clustered within each region. Associations between the clustered methylation and the gene expression data sets generate candidate matches within a fixed neighborhood around each gene. Finally, the methylation-expression associations are ranked through a logistic regression, and their significance is quantified through permutation analysis. Our two-step dimensionality reduction compressed 90% of the original data, reducing 137,688 methylation sites to 14,505 clusters. Methylation-expression associations produced 18,312 correspondences, which were used to further analyze epigenetic regulation. Logistic regression was used to identify 58 genes from these correspondences that showed a statistically significant negative correlation between methylation profiles and gene expression in the panel of breast cancer cell lines. Subnetwork enrichment of these genes has identified 35 common regulators with 6 or more predicted markers. In addition to identifying epigenetically regulated genes, we show evidence of differentially expressed methylation patterns between the basal and luminal subtypes. Our results indicate that the proposed computational protocol is a viable platform for identifying epigenetically regulated genes. Our protocol has generated a list of predictors including COL1A2, TOP2A, TFF1, and VAV3, genes whose key roles in epigenetic regulation is documented in the literature. Subnetwork enrichment of these predicted markers further suggests that epigenetic regulation of individual genes occurs in a coordinated fashion and through common regulators.
Autonomous Operations System: Development and Application
NASA Technical Reports Server (NTRS)
Toro Medina, Jaime A.; Wilkins, Kim N.; Walker, Mark; Stahl, Gerald M.
2016-01-01
Autonomous control systems provides the ability of self-governance beyond the conventional control system. As the complexity of mechanical and electrical systems increases, there develops a natural drive for developing robust control systems to manage complicated operations. By closing the bridge between conventional automated systems to knowledge based self-awareness systems, nominal control of operations can evolve into relying on safe critical mitigation processes to support any off-nominal behavior. Current research and development efforts lead by the Autonomous Propellant Loading (APL) group at NASA Kennedy Space Center aims to improve cryogenic propellant transfer operations by developing an automated control and health monitoring system. As an integrated systems, the center aims to produce an Autonomous Operations System (AOS) capable of integrating health management operations with automated control to produce a fully autonomous system.
Code of Federal Regulations, 2011 CFR
2011-10-01
... TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Traffic Control Systems Standards § 236.401 Automatic... 49 Transportation 4 2011-10-01 2011-10-01 false Automatic block signal system and interlocking standards applicable to traffic control systems. 236.401 Section 236.401 Transportation Other Regulations...
Digital control analysis and design of a field-sensed magnetic suspension system.
Li, Jen-Hsing; Chiou, Juing-Shian
2015-03-13
Magnetic suspension systems are mechatronic systems and crucial in several engineering applications, such as the levitation of high-speed trains, frictionless bearings, and wind tunnels. Magnetic suspension systems are nonlinear and unstable systems; therefore, they are suitable educational benchmarks for testing various modeling and control methods. This paper presents the digital modeling and control of magnetic suspension systems. First, the magnetic suspension system is stabilized using a digital proportional-derivative controller. Subsequently, the digital model is identified using recursive algorithms. Finally, a digital mixed linear quadratic regulator (LQR)/H∞ control is adopted to stabilize the magnetic suspension system robustly. Simulation examples and a real-world example are provided to demonstrate the practicality of the study results. In this study, a digital magnetic suspension system model was developed and reviewed. In addition, equivalent state and output feedback controls for magnetic suspension systems were developed. Using this method, the controller design for magnetic suspension systems was simplified, which is the novel contribution of this study. In addition, this paper proposes a complete digital controller design procedure for magnetic suspension systems.
Robust high-performance control for robotic manipulators
NASA Technical Reports Server (NTRS)
Seraji, Homayoun (Inventor)
1991-01-01
Model-based and performance-based control techniques are combined for an electrical robotic control system. Thus, two distinct and separate design philosophies have been merged into a single control system having a control law formulation including two distinct and separate components, each of which yields a respective signal component that is combined into a total command signal for the system. Those two separate system components include a feedforward controller and a feedback controller. The feedforward controller is model-based and contains any known part of the manipulator dynamics that can be used for on-line control to produce a nominal feedforward component of the system's control signal. The feedback controller is performance-based and consists of a simple adaptive PID controller which generates an adaptive control signal to complement the nominal feedforward signal.
Robust high-performance control for robotic manipulators
NASA Technical Reports Server (NTRS)
Seraji, Homayoun (Inventor)
1989-01-01
Model-based and performance-based control techniques are combined for an electrical robotic control system. Thus, two distinct and separate design philosophies were merged into a single control system having a control law formulation including two distinct and separate components, each of which yields a respective signal componet that is combined into a total command signal for the system. Those two separate system components include a feedforward controller and feedback controller. The feedforward controller is model-based and contains any known part of the manipulator dynamics that can be used for on-line control to produce a nominal feedforward component of the system's control signal. The feedback controller is performance-based and consists of a simple adaptive PID controller which generates an adaptive control signal to complement the nomical feedforward signal.
Robust approximation-free prescribed performance control for nonlinear systems and its application
NASA Astrophysics Data System (ADS)
Sun, Ruisheng; Na, Jing; Zhu, Bin
2018-02-01
This paper presents a robust prescribed performance control approach and its application to nonlinear tail-controlled missile systems with unknown dynamics and uncertainties. The idea of prescribed performance function (PPF) is incorporated into the control design, such that both the steady-state and transient control performance can be strictly guaranteed. Unlike conventional PPF-based control methods, we further tailor a recently proposed systematic control design procedure (i.e. approximation-free control) using the transformed tracking error dynamics, which provides a proportional-like control action. Hence, the function approximators (e.g. neural networks, fuzzy systems) that are widely used to address the unknown nonlinearities in the nonlinear control designs are not needed. The proposed control design leads to a robust yet simplified function approximation-free control for nonlinear systems. The closed-loop system stability and the control error convergence are all rigorously proved. Finally, comparative simulations are conducted based on nonlinear missile systems to validate the improved response and the robustness of the proposed control method.
Real-Time Adaptive Control of a Magnetic Levitation System with a Large Range of Load Disturbance.
Zhang, Zhizhou; Li, Xiaolong
2018-05-11
In an idle light-load or a full-load condition, the change of the load mass of a suspension system is very significant. If the control parameters of conventional control methods remain unchanged, the suspension performance of the control system deteriorates rapidly or even loses stability when the load mass changes in a large range. In this paper, a real-time adaptive control method for a magnetic levitation system with large range of mass changes is proposed. First, the suspension control system model of the maglev train is built up, and the stability of the closed-loop system is analyzed. Then, a fast inner current-loop is used to simplify the design of the suspension control system, and an adaptive control method is put forward to ensure that the system is still in a stable state when the load mass varies in a wide range. Simulations and experiments show that when the load mass of the maglev system varies greatly, the adaptive control method is effective to suspend the system stably with a given displacement.
Real-Time Adaptive Control of a Magnetic Levitation System with a Large Range of Load Disturbance
Zhang, Zhizhou; Li, Xiaolong
2018-01-01
In an idle light-load or a full-load condition, the change of the load mass of a suspension system is very significant. If the control parameters of conventional control methods remain unchanged, the suspension performance of the control system deteriorates rapidly or even loses stability when the load mass changes in a large range. In this paper, a real-time adaptive control method for a magnetic levitation system with large range of mass changes is proposed. First, the suspension control system model of the maglev train is built up, and the stability of the closed-loop system is analyzed. Then, a fast inner current-loop is used to simplify the design of the suspension control system, and an adaptive control method is put forward to ensure that the system is still in a stable state when the load mass varies in a wide range. Simulations and experiments show that when the load mass of the maglev system varies greatly, the adaptive control method is effective to suspend the system stably with a given displacement. PMID:29751610
Pegasus power system facility upgrades
NASA Astrophysics Data System (ADS)
Lewicki, B. T.; Kujak-Ford, B. A.; Winz, G. R.
2008-11-01
Two key Pegasus systems have been recently upgraded: the Ohmic-transformer IGCT bridge control system, and the plasma-gun injector power system. The Ohmic control system contains two new microprocessor controlled components to provide an interface between the PWM controller and the IGCT bridges. An interface board conditions the command signals from the PWM controller. A splitter/combiner board routes the conditioned PWM commands to an array of IGCT bridges and interprets IGCT bridge status. This system allows for any PWM controller to safely control IGCT bridges. Future developments will include a transition to a polyphasic bridge control. This will allow for 3 to 4 times the present pulse length and provide a much higher switching frequency. The plasma gun injector system now includes active current feedback control on gun bias current via PWM buck type power supplies. Near term goals include a doubling or tripling of the applied bias voltage. Future arc bias system power supplies may include a simpler boost type system which will allow access to even higher voltages using existing low voltage energy storage systems.
Cyber Security Assessment Report: Adventium Labs
DOE Office of Scientific and Technical Information (OSTI.GOV)
None
2007-12-31
Major control system components often have life spans of 15-20 years. Many systems in our Nation's critical infrastructure were installed before the Internet became a reality and security was a concern. Consequently, control systems are generally insecure. Security is now being included in the development of new control system devices; however, legacy control systems remain vulnerable. Most efforts to secure control systems are aimed at protecting network borers, but if an intruder gets inside the network these systems are vulnerable to a cyber attack.
NASA Technical Reports Server (NTRS)
Deckert, W. H.; Rolls, L. S.
1974-01-01
An integrated propulsion/control system for lift-fan transport aircraft is described. System behavior from full-scale experimental and piloted simulator investigations are reported. The lift-fan transport is a promising concept for short-to-medium haul civil transportation and for other missions. The lift-fan transport concept features high cruise airspeed, favorable ride qualities, small perceived noise footprints, high utilization, transportation system flexibility, and adaptability to VTOL, V/STOL, or STOL configurations. The lift-fan transport has high direct operating costs in comparison to conventional aircraft, primarily because of propulsion system and aircraft low-speed control system installation requirements. An integrated lift-fan propulsion system/aircraft low-speed control system that reduces total propulsion system and control system installation requirements is discussed.
Digital redesign of the control system for the Robotics Research Corporation model K-1607 robot
NASA Technical Reports Server (NTRS)
Carroll, Robert L.
1989-01-01
The analog control system for positioning each link of the Robotics Research Corporation Model K-1607 robot manipulator was redesigned for computer control. In order to accomplish the redesign, a linearized model of the dynamic behavior of the robot was developed. The parameters of the model were determined by examination of the input-output data collected in closed-loop operation of the analog control system. The robot manipulator possesses seven degrees of freedom in its motion. The analog control system installed by the manufacturer of the robot attempts to control the positioning of each link without feedback from other links. Constraints on the design of a digital control system include: the robot cannot be disassembled for measurement of parameters; the digital control system must not include filtering operations if possible, because of lack of computer capability; and criteria of goodness of control system performing is lacking. The resulting design employs sampled-data position and velocity feedback. The criteria of the design permits the control system gain margin and phase margin, measured at the same frequencies, to be the same as that provided by the analog control system.
NASA Technical Reports Server (NTRS)
Biezad, Daniel
1997-01-01
Handling qualities analysis and control law design would seem to be naturally complimenting components of aircraft flight control system design, however these two closely coupled disciplines are often not well integrated in practice. Handling qualities engineers and control system engineers may work in separate groups within an aircraft company. Flight control system engineers and handling quality specialists may come from different backgrounds and schooling and are often not aware of the other group's research. Thus while the handling qualities specifications represent desired aircraft response characteristics, these are rarely incorporated directly in the control system design process. Instead modem control system design techniques are based on servo-loop robustness specifications, and simple representations of the desired control response. Comprehensive handling qualities analysis is often left until the end of the design cycle and performed as a check of the completed design for satisfactory performance. This can lead to costly redesign or less than satisfactory aircraft handling qualities when the flight testing phase is reached. The desire to integrate the fields of handling qualities and flight,control systems led to the development of the CONDUIT system. This tool facilitates control system designs that achieve desired handling quality requirements and servo-loop specifications in a single design process. With CONDUIT, the control system engineer is now able to directly design and control systems to meet the complete handling specifications. CONDUIT allows the designer to retain a preferred control law structure, but then tunes the system parameters to meet the handling quality requirements.
NASA Technical Reports Server (NTRS)
Burgin, G. H.; Eggleston, D. M.
1976-01-01
A flight control system for use in air-to-air combat simulation was designed. The input to the flight control system are commanded bank angle and angle of attack, the output are commands to the control surface actuators such that the commanded values will be achieved in near minimum time and sideslip is controlled to remain small. For the longitudinal direction, a conventional linear control system with gains scheduled as a function of dynamic pressure is employed. For the lateral direction, a novel control system, consisting of a linear portion for small bank angle errors and a bang-bang control system for large errors and error rates is employed.
Flight-determined benefits of integrated flight-propulsion control systems
NASA Technical Reports Server (NTRS)
Stewart, James F.; Burcham, Frank W., Jr.; Gatlin, Donald H.
1992-01-01
Over the last two decades, NASA has conducted several experiments in integrated flight-propulsion control. Benefits have included improved maneuverability; increased thrust, range, and survivability; reduced fuel consumption; and reduced maintenance. This paper presents the basic concepts for control integration, examples of implementation, and benefits. The F-111E experiment integrated the engine and inlet control systems. The YF-12C incorporated an integral control system involving the inlet, autopilot, autothrottle, airdata, navigation, and stability augmentation systems. The F-15 research involved integration of the engine, flight, and inlet control systems. Further extension of the integration included real-time, onboard optimization of engine, inlet, and flight control variables; a self-repairing flight control system; and an engines-only control concept for emergency control. The F-18A aircraft incorporated thrust vectoring integrated with the flight control system to provide enhanced maneuvering at high angles of attack. The flight research programs and the resulting benefits of each program are described.
Robust Fixed-Structure Controller Synthesis
NASA Technical Reports Server (NTRS)
Corrado, Joseph R.; Haddad, Wassim M.; Gupta, Kajal (Technical Monitor)
2000-01-01
The ability to develop an integrated control system design methodology for robust high performance controllers satisfying multiple design criteria and real world hardware constraints constitutes a challenging task. The increasingly stringent performance specifications required for controlling such systems necessitates a trade-off between controller complexity and robustness. The principle challenge of the minimal complexity robust control design is to arrive at a tractable control design formulation in spite of the extreme complexity of such systems. Hence, design of minimal complexitY robust controllers for systems in the face of modeling errors has been a major preoccupation of system and control theorists and practitioners for the past several decades.
Control technology for future aircraft propulsion systems
NASA Technical Reports Server (NTRS)
Zeller, J. R.; Szuch, J. R.; Merrill, W. C.; Lehtinen, B.; Soeder, J. F.
1984-01-01
The need for a more sophisticated engine control system is discussed. The improvements in better thrust-to-weight ratios demand the manipulation of more control inputs. New technological solutions to the engine control problem are practiced. The digital electronic engine control (DEEC) system is a step in the evolution to digital electronic engine control. Technology issues are addressed to ensure a growth in confidence in sophisticated electronic controls for aircraft turbine engines. The need of a control system architecture which permits propulsion controls to be functionally integrated with other aircraft systems is established. Areas of technology studied include: (1) control design methodology; (2) improved modeling and simulation methods; and (3) implementation technologies. Objectives, results and future thrusts are summarized.
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.
Design and Stability of an On-Orbit Attitude Control System Using Reaction Control Thrusters
NASA Technical Reports Server (NTRS)
Hall, Robert A.; Hough, Steven; Orphee, Carolina; Clements, Keith
2015-01-01
Principles for the design and stability of a spacecraft on-orbit attitude control system employing on-off Reaction Control System (RCS) thrusters is presented. Both the vehicle dynamics and the control system actuators are inherently nonlinear, hence traditional linear control system design approaches are not directly applicable. This paper has three main aspects: It summarizes key RCS control System design principles from the Space Shuttle and Space Station programs, it demonstrates a new approach to develop a linear model of a phase plane control system using describing functions, and applies each of these to the initial development of the NASA's next generation of upper stage vehicles. Topics addressed include thruster hardware specifications, phase plane design and stability, jet selection approaches, filter design metrics, and automaneuver logic.
NASA Astrophysics Data System (ADS)
Iakovleva, E. V.; Momot, B. A.
2017-10-01
The object of this study is to develop a power plant and an electric propulsion control system for autonomous remotely controlled vessels. The tasks of the study are as follows: to assess remotely controlled vessels usage reasonability, to define the requirements for this type of vessel navigation. In addition, the paper presents the analysis of technical diagnostics systems. The developed electric propulsion control systems for vessels should provide improved reliability and efficiency of the propulsion complex to ensure the profitability of remotely controlled vessels.
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
The current status of the Active Controls Technology (ACT) for the advanced subsonic transport project is investigated through analysis of the systems technical data. Control systems technologies under examination include computerized reliability analysis, pitch axis fly by wire actuator, flaperon actuation system design trade study, control law synthesis and analysis, flutter mode control and gust load alleviation analysis, and implementation of alternative ACT systems. Extensive analysis of the computer techniques involved in each system is included.
Control aspects of the Schuchuli Village stand-alone photovoltaic power system
NASA Astrophysics Data System (ADS)
Groumpos, P. P.; Culler, J. E.; Delombard, R.
1984-11-01
A photovoltaic power system in an Arizona Indian village was installed. The control subsystem of this photovoltaic power system was analyzed. The four major functions of the control subsystem are: (1) voltage regulation; (2) load management; (3) water pump control; and (4) system protection. The control subsystem functions flowcharts for the control subsystem operation, and a computer program that models the control subsystem are presented.
Control aspects of the Schuchuli Village stand-alone photovoltaic power system
NASA Technical Reports Server (NTRS)
Groumpos, P. P.; Culler, J. E.; Delombard, R.
1984-01-01
A photovoltaic power system in an Arizona Indian village was installed. The control subsystem of this photovoltaic power system was analyzed. The four major functions of the control subsystem are: (1) voltage regulation; (2) load management; (3) water pump control; and (4) system protection. The control subsystem functions flowcharts for the control subsystem operation, and a computer program that models the control subsystem are presented.
Wisdom Appliance Control System
NASA Astrophysics Data System (ADS)
Hendrick; Jheng, Jyun-Teng; Tsai, Chen-Chai; Liou, Jia-Wei; Wang, Zhi-Hao; Jong, Gwo-Jia
2017-07-01
Intelligent appliances wisdom involves security, home care, convenient and energy saving, but the home automation system is still one of the core unit, and also using micro-processing electronics technology to centralized and control the home electrical products and systems, such as: lighting, television, fan, air conditioning, stereo, it composed of front-controller systems and back-controller panels, user using front-controller to control command, and then through the back-controller to powered the device.
40 CFR 63.749 - Compliance dates and determinations.
Code of Federal Regulations, 2011 CFR
2011-07-01
... control system efficiency, Ek, as determined using the procedures specified in § 63.750(g) for control systems containing carbon adsorbers and in § 63.750(h) for control systems with other control devices, is... device is used, (A) The overall control system efficiency, Ek, as determined using the procedures...
40 CFR 63.749 - Compliance dates and determinations.
Code of Federal Regulations, 2013 CFR
2013-07-01
... control system efficiency, Ek, as determined using the procedures specified in § 63.750(g) for control systems containing carbon adsorbers and in § 63.750(h) for control systems with other control devices, is... device is used, (A) The overall control system efficiency, Ek, as determined using the procedures...
40 CFR 63.749 - Compliance dates and determinations.
Code of Federal Regulations, 2014 CFR
2014-07-01
... control system efficiency, Ek, as determined using the procedures specified in § 63.750(g) for control systems containing carbon adsorbers and in § 63.750(h) for control systems with other control devices, is... device is used, (A) The overall control system efficiency, Ek, as determined using the procedures...
40 CFR 63.749 - Compliance dates and determinations.
Code of Federal Regulations, 2012 CFR
2012-07-01
... control system efficiency, Ek, as determined using the procedures specified in § 63.750(g) for control systems containing carbon adsorbers and in § 63.750(h) for control systems with other control devices, is... device is used, (A) The overall control system efficiency, Ek, as determined using the procedures...
46 CFR 184.620 - Propulsion engine control systems.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 7 2014-10-01 2014-10-01 false Propulsion engine control systems. 184.620 Section 184... Communications Systems § 184.620 Propulsion engine control systems. (a) A vessel must have two independent means of controlling each propulsion engine. Control must be provided for the engine speed, direction of...
46 CFR 184.620 - Propulsion engine control systems.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 7 2013-10-01 2013-10-01 false Propulsion engine control systems. 184.620 Section 184... Communications Systems § 184.620 Propulsion engine control systems. (a) A vessel must have two independent means of controlling each propulsion engine. Control must be provided for the engine speed, direction of...
46 CFR 62.35-5 - Remote propulsion-control systems.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 2 2014-10-01 2014-10-01 false Remote propulsion-control systems. 62.35-5 Section 62.35... AUTOMATION Requirements for Specific Types of Automated Vital Systems § 62.35-5 Remote propulsion-control systems. (a) Manual propulsion control. All vessels having remote propulsion control from the navigating...
46 CFR 62.35-5 - Remote propulsion-control systems.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 2 2013-10-01 2013-10-01 false Remote propulsion-control systems. 62.35-5 Section 62.35... AUTOMATION Requirements for Specific Types of Automated Vital Systems § 62.35-5 Remote propulsion-control systems. (a) Manual propulsion control. All vessels having remote propulsion control from the navigating...
46 CFR 184.620 - Propulsion engine control systems.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 7 2011-10-01 2011-10-01 false Propulsion engine control systems. 184.620 Section 184... Communications Systems § 184.620 Propulsion engine control systems. (a) A vessel must have two independent means of controlling each propulsion engine. Control must be provided for the engine speed, direction of...
46 CFR 62.35-5 - Remote propulsion-control systems.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 2 2011-10-01 2011-10-01 false Remote propulsion-control systems. 62.35-5 Section 62.35... AUTOMATION Requirements for Specific Types of Automated Vital Systems § 62.35-5 Remote propulsion-control systems. (a) Manual propulsion control. All vessels having remote propulsion control from the navigating...
46 CFR 62.35-5 - Remote propulsion-control systems.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 2 2010-10-01 2010-10-01 false Remote propulsion-control systems. 62.35-5 Section 62.35... AUTOMATION Requirements for Specific Types of Automated Vital Systems § 62.35-5 Remote propulsion-control systems. (a) Manual propulsion control. All vessels having remote propulsion control from the navigating...
46 CFR 184.620 - Propulsion engine control systems.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 7 2012-10-01 2012-10-01 false Propulsion engine control systems. 184.620 Section 184... Communications Systems § 184.620 Propulsion engine control systems. (a) A vessel must have two independent means of controlling each propulsion engine. Control must be provided for the engine speed, direction of...
46 CFR 184.620 - Propulsion engine control systems.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 7 2010-10-01 2010-10-01 false Propulsion engine control systems. 184.620 Section 184... Communications Systems § 184.620 Propulsion engine control systems. (a) A vessel must have two independent means of controlling each propulsion engine. Control must be provided for the engine speed, direction of...
46 CFR 62.25-15 - Safety control systems.
Code of Federal Regulations, 2011 CFR
2011-10-01
....35-50. Note: Safety control systems include automatic and manual safety trip controls and automatic... engines. (e) Automatic safety trip control systems must— (1) Be provided where there is an immediate... 46 Shipping 2 2011-10-01 2011-10-01 false Safety control systems. 62.25-15 Section 62.25-15...
40 CFR 63.749 - Compliance dates and determinations.
Code of Federal Regulations, 2010 CFR
2010-07-01
... control system efficiency, Ek, as determined using the procedures specified in § 63.750(g) for control systems containing carbon adsorbers and in § 63.750(h) for control systems with other control devices, is... device is used, (A) The overall control system efficiency, Ek, as determined using the procedures...
49 CFR 229.13 - Control of locomotives.
Code of Federal Regulations, 2010 CFR
2010-10-01
... coupled in remote or multiple control, the propulsion system, the sanders, and the power brake system of each locomotive shall respond to control from the cab of the controlling locomotive. If a dynamic brake or regenerative brake system is in use, that portion of the system in use shall respond to control...
Development of a Self-Balancing Human Transportation Vehicle for the Teaching of Feedback Control
ERIC Educational Resources Information Center
Lin, Shui-Chun; Tsai, Ching-Chih
2009-01-01
Control systems education often needs to design interesting hands-on exercises that keep students interested in the control theory presented in lectures. These exercises include system modeling, system analyses, controller syntheses, implementation, experimentation, and performance evaluation of a control system. This paper presents an interesting…
49 CFR 236.1045 - Training specific to office control personnel.
Code of Federal Regulations, 2010 CFR
2010-10-01
... between the computer-aided dispatching system and the train control system, with respect to the safe... INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Positive Train Control Systems § 236.1045 Training specific to office control personnel. (a) Any person...
49 CFR 236.1045 - Training specific to office control personnel.
Code of Federal Regulations, 2014 CFR
2014-10-01
... between the computer-aided dispatching system and the train control system, with respect to the safe... INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Positive Train Control Systems § 236.1045 Training specific to office control personnel. (a) Any person...
49 CFR 236.925 - Training specific to control office personnel.
Code of Federal Regulations, 2013 CFR
2013-10-01
... concerning the interface between the computer-aided dispatching system and the train control system, with... INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Standards for Processor-Based Signal and Train Control Systems § 236.925 Training specific to control office...
49 CFR 236.1045 - Training specific to office control personnel.
Code of Federal Regulations, 2012 CFR
2012-10-01
... between the computer-aided dispatching system and the train control system, with respect to the safe... INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Positive Train Control Systems § 236.1045 Training specific to office control personnel. (a) Any person...
49 CFR 236.925 - Training specific to control office personnel.
Code of Federal Regulations, 2011 CFR
2011-10-01
... concerning the interface between the computer-aided dispatching system and the train control system, with... INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Standards for Processor-Based Signal and Train Control Systems § 236.925 Training specific to control office...
49 CFR 236.925 - Training specific to control office personnel.
Code of Federal Regulations, 2012 CFR
2012-10-01
... concerning the interface between the computer-aided dispatching system and the train control system, with... INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Standards for Processor-Based Signal and Train Control Systems § 236.925 Training specific to control office...
49 CFR 236.1045 - Training specific to office control personnel.
Code of Federal Regulations, 2011 CFR
2011-10-01
... between the computer-aided dispatching system and the train control system, with respect to the safe... INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Positive Train Control Systems § 236.1045 Training specific to office control personnel. (a) Any person...
49 CFR 236.925 - Training specific to control office personnel.
Code of Federal Regulations, 2010 CFR
2010-10-01
... concerning the interface between the computer-aided dispatching system and the train control system, with... INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Standards for Processor-Based Signal and Train Control Systems § 236.925 Training specific to control office...
49 CFR 236.1045 - Training specific to office control personnel.
Code of Federal Regulations, 2013 CFR
2013-10-01
... between the computer-aided dispatching system and the train control system, with respect to the safe... INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Positive Train Control Systems § 236.1045 Training specific to office control personnel. (a) Any person...
49 CFR 236.925 - Training specific to control office personnel.
Code of Federal Regulations, 2014 CFR
2014-10-01
... concerning the interface between the computer-aided dispatching system and the train control system, with... INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Standards for Processor-Based Signal and Train Control Systems § 236.925 Training specific to control office...
14 CFR 29.395 - Control system.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Control system. 29.395 Section 29.395... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Strength Requirements Control Surface and System Loads § 29.395 Control system. (a) The reaction to the loads prescribed in § 29.397 must be provided by— (1) The control...
14 CFR 25.679 - Control system gust locks.
Code of Federal Regulations, 2014 CFR
2014-01-01
... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Control Systems § 25.679 Control system gust locks. (a) There must be a device to prevent damage to the control surfaces (including tabs... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Control system gust locks. 25.679 Section...
14 CFR 25.679 - Control system gust locks.
Code of Federal Regulations, 2012 CFR
2012-01-01
... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Control Systems § 25.679 Control system gust locks. (a) There must be a device to prevent damage to the control surfaces (including tabs... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Control system gust locks. 25.679 Section...
14 CFR 25.679 - Control system gust locks.
Code of Federal Regulations, 2011 CFR
2011-01-01
... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Control Systems § 25.679 Control system gust locks. (a) There must be a device to prevent damage to the control surfaces (including tabs... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Control system gust locks. 25.679 Section...
14 CFR 25.679 - Control system gust locks.
Code of Federal Regulations, 2010 CFR
2010-01-01
... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Control Systems § 25.679 Control system gust locks. (a) There must be a device to prevent damage to the control surfaces (including tabs... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Control system gust locks. 25.679 Section...
46 CFR 62.35-5 - Remote propulsion-control systems.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 2 2012-10-01 2012-10-01 false Remote propulsion-control systems. 62.35-5 Section 62.35... AUTOMATION Requirements for Specific Types of Automated Vital Systems § 62.35-5 Remote propulsion-control systems. (a) Manual propulsion control. All vessels having remote propulsion control from the navigating...
49 CFR 236.825 - System, automatic train control.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 4 2010-10-01 2010-10-01 false System, automatic train control. 236.825 Section..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.825 System, automatic train control. A system so arranged that its operation will automatically...
49 CFR 236.825 - System, automatic train control.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 49 Transportation 4 2011-10-01 2011-10-01 false System, automatic train control. 236.825 Section..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.825 System, automatic train control. A system so arranged that its operation will automatically...
Adaptive Control for Autonomous Navigation of Mobile Robots Considering Time Delay and Uncertainty
NASA Astrophysics Data System (ADS)
Armah, Stephen Kofi
Autonomous control of mobile robots has attracted considerable attention of researchers in the areas of robotics and autonomous systems during the past decades. One of the goals in the field of mobile robotics is development of platforms that robustly operate in given, partially unknown, or unpredictable environments and offer desired services to humans. Autonomous mobile robots need to be equipped with effective, robust and/or adaptive, navigation control systems. In spite of enormous reported work on autonomous navigation control systems for mobile robots, achieving the goal above is still an open problem. Robustness and reliability of the controlled system can always be improved. The fundamental issues affecting the stability of the control systems include the undesired nonlinear effects introduced by actuator saturation, time delay in the controlled system, and uncertainty in the model. This research work develops robustly stabilizing control systems by investigating and addressing such nonlinear effects through analytical, simulations, and experiments. The control systems are designed to meet specified transient and steady-state specifications. The systems used for this research are ground (Dr Robot X80SV) and aerial (Parrot AR.Drone 2.0) mobile robots. Firstly, an effective autonomous navigation control system is developed for X80SV using logic control by combining 'go-to-goal', 'avoid-obstacle', and 'follow-wall' controllers. A MATLAB robot simulator is developed to implement this control algorithm and experiments are conducted in a typical office environment. The next stage of the research develops an autonomous position (x, y, and z) and attitude (roll, pitch, and yaw) controllers for a quadrotor, and PD-feedback control is used to achieve stabilization. The quadrotor's nonlinear dynamics and kinematics are implemented using MATLAB S-function to generate the state output. Secondly, the white-box and black-box approaches are used to obtain a linearized second-order altitude models for the quadrotor, AR.Drone 2.0. Proportional (P), pole placement or proportional plus velocity (PV), linear quadratic regulator (LQR), and model reference adaptive control (MRAC) controllers are designed and validated through simulations using MATLAB/Simulink. Control input saturation and time delay in the controlled systems are also studied. MATLAB graphical user interface (GUI) and Simulink programs are developed to implement the controllers on the drone. Thirdly, the time delay in the drone's control system is estimated using analytical and experimental methods. In the experimental approach, the transient properties of the experimental altitude responses are compared to those of simulated responses. The analytical approach makes use of the Lambert W function to obtain analytical solutions of scalar first-order delay differential equations (DDEs). A time-delayed P-feedback control system (retarded type) is used in estimating the time delay. Then an improved system performance is obtained by incorporating the estimated time delay in the design of the PV control system (neutral type) and PV-MRAC control system. Furthermore, the stability of a parametric perturbed linear time-invariant (LTI) retarded-type system is studied. This is done by analytically calculating the stability radius of the system. Simulation of the control system is conducted to confirm the stability. This robust control design and uncertainty analysis are conducted for first-order and second-order quadrotor models. Lastly, the robustly designed PV and PV-MRAC control systems are used to autonomously track multiple waypoints. Also, the robustness of the PV-MRAC controller is tested against a baseline PV controller using the payload capability of the drone. It is shown that the PV-MRAC offers several benefits over the fixed-gain approach of the PV controller. The adaptive control is found to offer enhanced robustness to the payload fluctuations.
Distributed Engine Control Empirical/Analytical Verification Tools
NASA Technical Reports Server (NTRS)
DeCastro, Jonathan; Hettler, Eric; Yedavalli, Rama; Mitra, Sayan
2013-01-01
NASA's vision for an intelligent engine will be realized with the development of a truly distributed control system featuring highly reliable, modular, and dependable components capable of both surviving the harsh engine operating environment and decentralized functionality. A set of control system verification tools was developed and applied to a C-MAPSS40K engine model, and metrics were established to assess the stability and performance of these control systems on the same platform. A software tool was developed that allows designers to assemble easily a distributed control system in software and immediately assess the overall impacts of the system on the target (simulated) platform, allowing control system designers to converge rapidly on acceptable architectures with consideration to all required hardware elements. The software developed in this program will be installed on a distributed hardware-in-the-loop (DHIL) simulation tool to assist NASA and the Distributed Engine Control Working Group (DECWG) in integrating DCS (distributed engine control systems) components onto existing and next-generation engines.The distributed engine control simulator blockset for MATLAB/Simulink and hardware simulator provides the capability to simulate virtual subcomponents, as well as swap actual subcomponents for hardware-in-the-loop (HIL) analysis. Subcomponents can be the communication network, smart sensor or actuator nodes, or a centralized control system. The distributed engine control blockset for MATLAB/Simulink is a software development tool. The software includes an engine simulation, a communication network simulation, control algorithms, and analysis algorithms set up in a modular environment for rapid simulation of different network architectures; the hardware consists of an embedded device running parts of the CMAPSS engine simulator and controlled through Simulink. The distributed engine control simulation, evaluation, and analysis technology provides unique capabilities to study the effects of a given change to the control system in the context of the distributed paradigm. The simulation tool can support treatment of all components within the control system, both virtual and real; these include communication data network, smart sensor and actuator nodes, centralized control system (FADEC full authority digital engine control), and the aircraft engine itself. The DECsim tool can allow simulation-based prototyping of control laws, control architectures, and decentralization strategies before hardware is integrated into the system. With the configuration specified, the simulator allows a variety of key factors to be systematically assessed. Such factors include control system performance, reliability, weight, and bandwidth utilization.
Renewal of the Control System and Reliable Long Term Operation of the LHD Cryogenic System
NASA Astrophysics Data System (ADS)
Mito, T.; Iwamoto, A.; Oba, K.; Takami, S.; Moriuchi, S.; Imagawa, S.; Takahata, K.; Yamada, S.; Yanagi, N.; Hamaguchi, S.; Kishida, F.; Nakashima, T.
The Large Helical Device (LHD) is a heliotron-type fusion plasma experimental machine which consists of a fully superconducting magnet system cooled by a helium refrigerator having a total equivalent cooling capacity of 9.2 kW@4.4 K. Seventeenplasma experimental campaigns have been performed successfully since1997 with high reliability of 99%. However, sixteen years have passed from the beginning of the system operation. Improvements are being implementedto prevent serious failures and to pursue further reliability.The LHD cryogenic control system was designed and developed as an open system utilizing latest control equipment of VME controllers and UNIX workstations at the construction time. Howeverthe generation change of control equipment has been advanced. Down-sizing of control deviceshas beenplanned from VME controllers to compact PCI controllers in order to simplify the system configuration and to improve the system reliability. The new system is composed of compact PCI controller and remote I/O connected with EtherNet/IP. Making the system redundant becomes possible by doubling CPU, LAN, and remote I/O respectively. The smooth renewal of the LHD cryogenic controlsystem and the further improvement of the cryogenic system reliability are reported.
Comparison of digital controllers used in magnetic suspension and balance systems
NASA Technical Reports Server (NTRS)
Kilgore, William A.
1990-01-01
Dynamic systems that were once controlled by analog circuits are now controlled by digital computers. Presented is a comparison of the digital controllers presently used with magnetic suspension and balance systems. The overall responses of the systems are compared using a computer simulation of the magnetic suspension and balance system and the digital controllers. The comparisons include responses to both simulated force and position inputs. A preferred digital controller is determined from the simulated responses.
3. EAGLE ROCK CONTROL CENTER, OPERATIONS CONTROL. AS SYSTEM BECOMES ...
3. EAGLE ROCK CONTROL CENTER, OPERATIONS CONTROL. AS SYSTEM BECOMES INCREASINGLY AUTOMATED, EAGLE ROCK WILL BECOME MORE AND MORE THE CENTRAL CONTROL SYSTEM OF THE METROPOLITAN WATER DISTRICT. - Eagle Rock Operations Control Center, Pasadena, Los Angeles County, CA
Intelligent on-line fault tolerant control for unanticipated catastrophic failures.
Yen, Gary G; Ho, Liang-Wei
2004-10-01
As dynamic systems become increasingly complex, experience rapidly changing environments, and encounter a greater variety of unexpected component failures, solving the control problems of such systems is a grand challenge for control engineers. Traditional control design techniques are not adequate to cope with these systems, which may suffer from unanticipated dynamic failures. In this research work, we investigate the on-line fault tolerant control problem and propose an intelligent on-line control strategy to handle the desired trajectories tracking problem for systems suffering from various unanticipated catastrophic faults. Through theoretical analysis, the sufficient condition of system stability has been derived and two different on-line control laws have been developed. The approach of the proposed intelligent control strategy is to continuously monitor the system performance and identify what the system's current state is by using a fault detection method based upon our best knowledge of the nominal system and nominal controller. Once a fault is detected, the proposed intelligent controller will adjust its control signal to compensate for the unknown system failure dynamics by using an artificial neural network as an on-line estimator to approximate the unexpected and unknown failure dynamics. The first control law is derived directly from the Lyapunov stability theory, while the second control law is derived based upon the discrete-time sliding mode control technique. Both control laws have been implemented in a variety of failure scenarios to validate the proposed intelligent control scheme. The simulation results, including a three-tank benchmark problem, comply with theoretical analysis and demonstrate a significant improvement in trajectory following performance based upon the proposed intelligent control strategy.
Sliding Mode Thermal Control System for Space Station Furnace Facility
NASA Technical Reports Server (NTRS)
Jackson Mark E.; Shtessel, Yuri B.
1998-01-01
The decoupled control of the nonlinear, multiinput-multioutput, and highly coupled space station furnace facility (SSFF) thermal control system is addressed. Sliding mode control theory, a subset of variable-structure control theory, is employed to increase the performance, robustness, and reliability of the SSFF's currently designed control system. This paper presents the nonlinear thermal control system description and develops the sliding mode controllers that cause the interconnected subsystems to operate in their local sliding modes, resulting in control system invariance to plant uncertainties and external and interaction disturbances. The desired decoupled flow-rate tracking is achieved by optimization of the local linear sliding mode equations. The controllers are implemented digitally and extensive simulation results are presented to show the flow-rate tracking robustness and invariance to plant uncertainties, nonlinearities, external disturbances, and variations of the system pressure supplied to the controlled subsystems.
Advanced Ground Systems Maintenance Cryogenics Test Lab Control System Upgrade Project
NASA Technical Reports Server (NTRS)
Harp, Janice Leshay
2014-01-01
This project will outfit the Simulated Propellant Loading System (SPLS) at KSC's Cryogenics Test Laboratory with a new programmable logic control system. The control system upgrade enables the Advanced Ground Systems Maintenace Element Integration Team and other users of the SPLS to conduct testing in a controls environment similar to that used at the launch pad.
2007-03-01
Finite -dimensional regulators for a class of infinite dimensional systems ,” Systems and Control Letters, 3 (1983), 7-12. [11] B...semiglobal stabilizability by encoded state feedback,” to appear in Systems and Control Letters. 22 29. C. De Persis, A. Isidori, “Global stabilization of...nonequilibrium setting, for both finite and infinite dimensional control systems . Our objectives for distributed parameter systems included
Hybrid Control for Multi-Agent Systems in Complex Sensing Environments
2012-02-28
controllers , the overall closed-loop system is time -varying but can potentially exhibit better stability and performance... system is time -varying and yet, once 4 feedback-interconnected with a suitable controller , it can potentially yield better stability and performance...resolution Sensing, Control and Switched Systems 13 4 Metric-Based Receding Horizon Control 14 5 Decentralized Control and Finite Wordlength Channels 15
Microprocessor-based control systems application in nuclear power plant critical systems
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shah, M.R.; Nowak, J.B.
Microprocessor-based control systems have been used in fossil power plants and are receiving greater acceptance for application in nuclear plants. This technology is not new but it does require unique considerations when applied to nuclear power plants. Sargent and Lundy (S and L) has used a microprocessor-based component logic control system (interposing Logic System) for safety- and non-safety-related components in nuclear power plants under construction overseas. Currently, S and L is in the design stage to replace an existing analog control system with a microprocessor-based control system in the U.S. The trend in the industry is to replace systems inmore » existing plants or design new power plants with microprocessor-based control systems.« less
Minimal-Inversion Feedforward-And-Feedback Control System
NASA Technical Reports Server (NTRS)
Seraji, Homayoun
1990-01-01
Recent developments in theory of control systems support concept of minimal-inversion feedforward-and feedback control system consisting of three independently designable control subsystems. Applicable to the control of linear, time-invariant plant.
Application of a microcomputer-based system to control and monitor bacterial growth.
Titus, J A; Luli, G W; Dekleva, M L; Strohl, W R
1984-02-01
A modular microcomputer-based system was developed to control and monitor various modes of bacterial growth. The control system was composed of an Apple II Plus microcomputer with 64-kilobyte random-access memory; a Cyborg ISAAC model 91A multichannel analog-to-digital and digital-to-analog converter; paired MRR-1 pH, pO(2), and foam control units; and in-house-designed relay, servo control, and turbidimetry systems. To demonstrate the flexibility of the system, we grew bacteria under various computer-controlled and monitored modes of growth, including batch, turbidostat, and chemostat systems. The Apple-ISAAC system was programmed in Labsoft BASIC (extended Applesoft) with an average control program using ca. 6 to 8 kilobytes of memory and up to 30 kilobytes for datum arrays. This modular microcomputer-based control system was easily coupled to laboratory scale fermentors for a variety of fermentations.
Application of a Microcomputer-Based System to Control and Monitor Bacterial Growth
Titus, Jeffrey A.; Luli, Gregory W.; Dekleva, Michael L.; Strohl, William R.
1984-01-01
A modular microcomputer-based system was developed to control and monitor various modes of bacterial growth. The control system was composed of an Apple II Plus microcomputer with 64-kilobyte random-access memory; a Cyborg ISAAC model 91A multichannel analog-to-digital and digital-to-analog converter; paired MRR-1 pH, pO2, and foam control units; and in-house-designed relay, servo control, and turbidimetry systems. To demonstrate the flexibility of the system, we grew bacteria under various computer-controlled and monitored modes of growth, including batch, turbidostat, and chemostat systems. The Apple-ISAAC system was programmed in Labsoft BASIC (extended Applesoft) with an average control program using ca. 6 to 8 kilobytes of memory and up to 30 kilobytes for datum arrays. This modular microcomputer-based control system was easily coupled to laboratory scale fermentors for a variety of fermentations. PMID:16346462
An adaptive load-following control system for a space nuclear power system
NASA Astrophysics Data System (ADS)
Metzger, John D.; El-Genk, Mohamed S.
An adaptive load-following control system is proposed for a space nuclear power system. The conceptual design of the SP-100 space nuclear power system proposes operating the nuclear reactor at a base thermal power and accommodating changes in the electrical power demand with a shunt regulator. It is necessary to increase the reactor thermal power if the payload electrical demand exceeds the peak system electrical output for the associated reactor power. When it is necessary to change the nuclear reactor power to meet a change in the power demand, the power ascension or descension must be accomplished in a predetermined manner to avoid thermal stresses in the system and to achieve the desired reactor period. The load-following control system described has the ability to adapt to changes in the system and to changes in the satellite environment. The application is proposed of the model reference adaptive control (MRAC). The adaptive control system has the ability to control the dynamic response of nonlinear systems. Three basic subsets of adaptive control are: (1) gain scheduling, (2) self-tuning regulators, and (3) model reference adaptive control.
NASA Technical Reports Server (NTRS)
Cull, R. C.; Eltimsahy, A. H.
1983-01-01
The present investigation is concerned with the formulation of energy management strategies for stand-alone photovoltaic (PV) systems, taking into account a basic control algorithm for a possible predictive, (and adaptive) controller. The control system controls the flow of energy in the system according to the amount of energy available, and predicts the appropriate control set-points based on the energy (insolation) available by using an appropriate system model. Aspects of adaptation to the conditions of the system are also considered. Attention is given to a statistical analysis technique, the analysis inputs, the analysis procedure, and details regarding the basic control algorithm.
Energy Efficient Engine: Control system preliminary definition report
NASA Technical Reports Server (NTRS)
Howe, David C.
1986-01-01
The object of the Control Preliminary Definition Program was to define a preliminary control system concept as a part of the Energy Efficient Engine program. The program was limited to a conceptual definition of a full authority digital electronic control system. System requirements were determined and a control system was conceptually defined to these requirements. Areas requiring technological development were identified and a plan was established for implementing the identified technological features, including a control technology demonstration. A significant element of this program was a study of the potential benefits of closed-loop active clearance control, along with laboratory tests of candidate clearance sensor elements for a closed loop system.
Advanced controls for light sources
NASA Astrophysics Data System (ADS)
Biedron, S. G.; Edelen, A. L.; Milton, S. V.
2016-09-01
We present a summary of our team's recent efforts in developing adaptive, artificial intelligence-inspired techniques specifically to address several control challenges that arise in machines/systems including those in particle accelerator systems. These techniques can readily be adapted to other systems such as lasers, beamline optics, etc… We are not at all suggesting that we create an autonomous system, but create a system with an intelligent control system, that can continually use operational data to improve itself and combines both traditional and advanced techniques. We believe that the system performance and reliability can be increased based on our findings. Another related point is that the controls sub-system of an overall system is usually not the heart of the system architecture or design process. More bluntly, often times all of the peripheral systems are considered as secondary to the main system components in the architecture design process because it is assumed that the controls system will be able to "fix" challenges found later with the sub-systems for overall system operation. We will show that this is not always the case and that it took an intelligent control application to overcome a sub-system's challenges. We will provide a recent example of such a "fix" with a standard controller and with an artificial intelligence-inspired controller. A final related point to be covered is that of system adaptation for requirements not original to a system's original design.
NASA Astrophysics Data System (ADS)
Shukla, Jaikaran N.; Halfen, Frank J.; Brynsvold, Glen V.; Syed, Akbar; Jiang, Thomas J.; Wong, Kwok K.; Otwell, Robert L.
1994-07-01
Recent work in lower power generic early applications for the SP-100 have resulted in control system design simplification for a 20 kWe design with thermoelectric power conversion. This paper presents the non-mission-dependent control system features for this design. The control system includes a digital computer based controller, dual purpose control rods and drives, temperature sensors, and neutron flux monitors. The thaw system is mission dependent and can be either electrical or based on NaK trace lines. Key features of the control system and components are discussed. As was the case for higher power applications, the initial on-orbit approach to criticality involves the relatively fast withdrawal of the control-rods to a near-critical position followed by slower movement through critical and into the power range. The control system performs operating maneuvers as well as providing for automatic startup, shutdown, restart, and reactor protection.
Application of digital computer APU modeling techniques to control system design.
NASA Technical Reports Server (NTRS)
Bailey, D. A.; Burriss, W. L.
1973-01-01
Study of the required controls for a H2-O2 auxiliary power unit (APU) technology program for the Space Shuttle. A steady-state system digital computer program was prepared and used to optimize initial system design. Analytical models of each system component were included. The program was used to solve a nineteen-dimensional problem, and then time-dependent differential equations were added to the computer program to simulate transient APU system and control. Some system parameters were considered quasi-steady-state, and others were treated as differential variables. The dynamic control analysis proceeded from initial ideal control modeling (which considered one control function and assumed the others to be ideal), stepwise through the system (adding control functions), until all of the control functions and their interactions were considered. In this way, the adequacy of the final control design over the required wide range of APU operating conditions was established.
Sugiura, Haruka; Ito, Manami; Okuaki, Tomoya; Mori, Yoshihito; Kitahata, Hiroyuki; Takinoue, Masahiro
2016-01-01
The design, construction and control of artificial self-organized systems modelled on dynamical behaviours of living systems are important issues in biologically inspired engineering. Such systems are usually based on complex reaction dynamics far from equilibrium; therefore, the control of non-equilibrium conditions is required. Here we report a droplet open-reactor system, based on droplet fusion and fission, that achieves dynamical control over chemical fluxes into/out of the reactor for chemical reactions far from equilibrium. We mathematically reveal that the control mechanism is formulated as pulse-density modulation control of the fusion–fission timing. We produce the droplet open-reactor system using microfluidic technologies and then perform external control and autonomous feedback control over autocatalytic chemical oscillation reactions far from equilibrium. We believe that this system will be valuable for the dynamical control over self-organized phenomena far from equilibrium in chemical and biomedical studies. PMID:26786848
Sugiura, Haruka; Ito, Manami; Okuaki, Tomoya; Mori, Yoshihito; Kitahata, Hiroyuki; Takinoue, Masahiro
2016-01-20
The design, construction and control of artificial self-organized systems modelled on dynamical behaviours of living systems are important issues in biologically inspired engineering. Such systems are usually based on complex reaction dynamics far from equilibrium; therefore, the control of non-equilibrium conditions is required. Here we report a droplet open-reactor system, based on droplet fusion and fission, that achieves dynamical control over chemical fluxes into/out of the reactor for chemical reactions far from equilibrium. We mathematically reveal that the control mechanism is formulated as pulse-density modulation control of the fusion-fission timing. We produce the droplet open-reactor system using microfluidic technologies and then perform external control and autonomous feedback control over autocatalytic chemical oscillation reactions far from equilibrium. We believe that this system will be valuable for the dynamical control over self-organized phenomena far from equilibrium in chemical and biomedical studies.
A discrete control model of PLANT
NASA Technical Reports Server (NTRS)
Mitchell, C. M.
1985-01-01
A model of the PLANT system using the discrete control modeling techniques developed by Miller is described. Discrete control models attempt to represent in a mathematical form how a human operator might decompose a complex system into simpler parts and how the control actions and system configuration are coordinated so that acceptable overall system performance is achieved. Basic questions include knowledge representation, information flow, and decision making in complex systems. The structure of the model is a general hierarchical/heterarchical scheme which structurally accounts for coordination and dynamic focus of attention. Mathematically, the discrete control model is defined in terms of a network of finite state systems. Specifically, the discrete control model accounts for how specific control actions are selected from information about the controlled system, the environment, and the context of the situation. The objective is to provide a plausible and empirically testable accounting and, if possible, explanation of control behavior.
Remote control of microcontroller-based infant stimulating system.
Burunkaya, M; Güler, I
2000-04-01
In this paper, a remote-controlled and microcontroller-based cradle is designed and constructed. This system is also called Remote Control of Microcontroller-Based Infant Stimulation System or the RECOMBIS System. Cradle is an infant stimulating system that provides relaxation and sleeping for the baby. RECOMBIS system is designed for healthy full-term newborns to provide safe infant care and provide relaxation and sleeping for the baby. A microcontroller-based electronic circuit was designed and implemented for RECOMBIS system. Electromagnets were controlled by 8-bit PIC16F84 microcontroller, which is programmed using MPASM package. The system works by entering preset values from the keyboard, or pulse code modulated radio frequency remote control system. The control of the system and the motion range were tested. The test results showed that the system provided a good performance.
14 CFR 417.305 - Command control system testing.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Command control system testing. 417.305..., DEPARTMENT OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety System § 417.305 Command control system testing. (a) General. (1) A command control system, including its subsystems and components must undergo...
14 CFR 417.305 - Command control system testing.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Command control system testing. 417.305..., DEPARTMENT OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety System § 417.305 Command control system testing. (a) General. (1) A command control system, including its subsystems and components must undergo...
14 CFR 417.305 - Command control system testing.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Command control system testing. 417.305..., DEPARTMENT OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety System § 417.305 Command control system testing. (a) General. (1) A command control system, including its subsystems and components must undergo...
14 CFR 417.305 - Command control system testing.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Command control system testing. 417.305..., DEPARTMENT OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety System § 417.305 Command control system testing. (a) General. (1) A command control system, including its subsystems and components must undergo...
14 CFR 417.305 - Command control system testing.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Command control system testing. 417.305..., DEPARTMENT OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety System § 417.305 Command control system testing. (a) General. (1) A command control system, including its subsystems and components must undergo...
46 CFR 154.904 - Inert gas system: Controls.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 5 2011-10-01 2011-10-01 false Inert gas system: Controls. 154.904 Section 154.904... STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Atmospheric Control in Cargo Containment Systems § 154.904 Inert gas system: Controls. The inert gas system...
Controllable Grid Interface Test System | Energy Systems Integration
Facility | NREL Controllable Grid Interface Test System Controllable Grid Interface Test System NREL's controllable grid interface (CGI) test system can reduce certification testing time and costs grid interface is the first test facility in the United States that has fault simulation capabilities
Decoupling control of vehicle chassis system based on neural network inverse system
NASA Astrophysics Data System (ADS)
Wang, Chunyan; Zhao, Wanzhong; Luan, Zhongkai; Gao, Qi; Deng, Ke
2018-06-01
Steering and suspension are two important subsystems affecting the handling stability and riding comfort of the chassis system. In order to avoid the interference and coupling of the control channels between active front steering (AFS) and active suspension subsystems (ASS), this paper presents a composite decoupling control method, which consists of a neural network inverse system and a robust controller. The neural network inverse system is composed of a static neural network with several integrators and state feedback of the original chassis system to approach the inverse system of the nonlinear systems. The existence of the inverse system for the chassis system is proved by the reversibility derivation of Interactor algorithm. The robust controller is based on the internal model control (IMC), which is designed to improve the robustness and anti-interference of the decoupled system by adding a pre-compensation controller to the pseudo linear system. The results of the simulation and vehicle test show that the proposed decoupling controller has excellent decoupling performance, which can transform the multivariable system into a number of single input and single output systems, and eliminate the mutual influence and interference. Furthermore, it has satisfactory tracking capability and robust performance, which can improve the comprehensive performance of the chassis system.
An Assessment of Vulnerabilities for Ship-based Control Systems
2009-09-01
VULNERABILITIES FOR SHIP- BASED CONTROL SYSTEMS by Richard Bensing September 2009 Thesis Advisor: Karen Burke Co-Advisor: George Dinolt...COVERED Master’s Thesis 4. TITLE AND SUBTITLE: An Assessment of Vulnerabilities for Ship- based Control Systems 6. AUTHOR(S) Richard Bensing 5...soft underbelly. Computer- based control systems form the heart of the critical infrastructure, and these control systems are riddled with rampant
Flight-determined benefits of integrated flight-propulsion control systems
NASA Technical Reports Server (NTRS)
Stewart, James F.; Burcham, Frank W., Jr.; Gatlin, Donald H.
1992-01-01
The fundamentals of control integration for propulsion are reviewed giving practical illustrations of its use to demonstrate the advantages of integration. Attention is given to the first integration propulsion-control systems (IPCSs) which was developed for the F-111E, and the integrated controller design is described that NASA developed for the YF-12C aircraft. The integrated control systems incorporate a range of aircraft components including the engine, inlet controls, autopilot, autothrottle, airdata, navigation, and/or stability-augmentation systems. Also described are emergency-control systems, onboard engine optimization, and thrust-vectoring control technologies developed for the F-18A and the F-15. Integrated flight-propulsion control systems are shown to enhance the thrust, range, and survivability of the aircraft while reducing fuel consumption and maintenance.
NASA Technical Reports Server (NTRS)
Glende, W. L. B.
1974-01-01
The design, fabrication and flight testing of a powered elevator system for the Augmentor Wing Jet STOL Research Aircraft (AWJSRA or Mod C-8A) are discussed. The system replaces a manual spring tab elevator control system that was unsatisfactory in the STOL flight regime. Pitch control in the AWJSRA is by means of a single elevator control surface. The elevator is used for both maneuver and trim control as the stabilizer is fixed. A fully powered, irreversible flight control system powered by dual hydraulic sources was designed. The existing control columns and single mechanical cable system of the AWJSRA have been retained as has been the basic elevator surface, except that the elevator spring tab is modified into a geared balance tab. The control surface is directly actuated by a dual tandem moving body actuator. Control signals are transmitted from the elevator aft quadrant to the actuator by a linkage system that includes a limited authority series servo actuator.
X-33 Attitude Control System Design for Ascent, Transition, and Entry Flight Regimes
NASA Technical Reports Server (NTRS)
Hall, Charles E.; Gallaher, Michael W.; Hendrix, Neal D.
1998-01-01
The Vehicle Control Systems Team at Marshall Space Flight Center, Systems Dynamics Laboratory, Guidance and Control Systems Division is designing under a cooperative agreement with Lockheed Martin Skunkworks, the Ascent, Transition, and Entry flight attitude control system for the X-33 experimental vehicle. Ascent flight control begins at liftoff and ends at linear aerospike main engine cutoff (NECO) while Transition and Entry flight control begins at MECO and concludes at the terminal area energy management (TAEM) interface. TAEM occurs at approximately Mach 3.0. This task includes not only the design of the vehicle attitude control systems but also the development of requirements for attitude control system components and subsystems. The X-33 attitude control system design is challenged by a short design cycle, the design environment (Mach 0 to about Mach 15), and the X-33 incremental test philosophy. The X-33 design-to-launch cycle of less than 3 years requires a concurrent design approach while the test philosophy requires design adaptation to vehicle variations that are a function of Mach number and mission profile. The flight attitude control system must deal with the mixing of aerosurfaces, reaction control thrusters, and linear aerospike engine control effectors and handle parasitic effects such as vehicle flexibility and propellant sloshing from the uniquely shaped propellant tanks. The attitude control system design is, as usual, closely linked to many other subsystems and must deal with constraints and requirements from these subsystems.
Phase Control in Nonlinear Systems
NASA Astrophysics Data System (ADS)
Zambrano, Samuel; Seoane, Jesús M.; Mariño, Inés P.; Sanjuán, Miguel A. F.; Meucci, Riccardo
The following sections are included: * Introduction * Phase Control of Chaos * Description of the model * Numerical exploration of phase control of chaos * Experimental evidence of phase control of chaos * Phase Control of Intermittency in Dynamical Systems * Crisis-induced intermittency and its control * Experimental setup and implementation of the phase control scheme * Phase control of the laser in the pre-crisis regime * Phase control of the intermittency after the crisis * Phase control of the intermittency in the quadratic map * Phase Control of Escapes in Open Dynamical Systems * Control of open dynamical systems * Model description * Numerical simulations and heuristic arguments * Experimental implementation in an electronic circuit * Conclusions and Discussions * Acknowledgments * References
Gao, Bingwei; Shao, Junpeng; Yang, Xiaodong
2014-11-01
In order to enhance the anti-jamming ability of electro-hydraulic position servo control system at the same time improve the control precision of the system, a compound control strategy that combines velocity compensation with Active Disturbance Rejection Controller (ADRC) is proposed, and the working principle of the compound control strategy is given. ADRC controller is designed, and the extended state observer is used for observing internal parameters uncertainties and external disturbances, so that the disturbances of the system are suppressed effectively. Velocity compensation controller is designed and the compensation model is derived to further improve the positioning accuracy of the system and to achieve the velocity compensation without disturbance. The compound control strategy is verified by the simulation and experiment respectively, and the simulation and experimental results show that the electro-hydraulic position servo control system with ADRC controller can effectively inhibit the external disturbances, the precise positioning control is realized after introducing the velocity compensation controller, and verify that the compound control strategy is effective. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.
Fuzzy model-based servo and model following control for nonlinear systems.
Ohtake, Hiroshi; Tanaka, Kazuo; Wang, Hua O
2009-12-01
This correspondence presents servo and nonlinear model following controls for a class of nonlinear systems using the Takagi-Sugeno fuzzy model-based control approach. First, the construction method of the augmented fuzzy system for continuous-time nonlinear systems is proposed by differentiating the original nonlinear system. Second, the dynamic fuzzy servo controller and the dynamic fuzzy model following controller, which can make outputs of the nonlinear system converge to target points and to outputs of the reference system, respectively, are introduced. Finally, the servo and model following controller design conditions are given in terms of linear matrix inequalities. Design examples illustrate the utility of this approach.
Motion control of musculoskeletal systems with redundancy.
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.
Control and optimization system and method for chemical looping processes
Lou, Xinsheng; Joshi, Abhinaya; Lei, Hao
2014-06-24
A control system for optimizing a chemical loop system includes one or more sensors for measuring one or more parameters in a chemical loop. The sensors are disposed on or in a conduit positioned in the chemical loop. The sensors generate one or more data signals representative of an amount of solids in the conduit. The control system includes a data acquisition system in communication with the sensors and a controller in communication with the data acquisition system. The data acquisition system receives the data signals and the controller generates the control signals. The controller is in communication with one or more valves positioned in the chemical loop. The valves are configured to regulate a flow of the solids through the chemical loop.
Control and optimization system and method for chemical looping processes
Lou, Xinsheng; Joshi, Abhinaya; Lei, Hao
2015-02-17
A control system for optimizing a chemical loop system includes one or more sensors for measuring one or more parameters in a chemical loop. The sensors are disposed on or in a conduit positioned in the chemical loop. The sensors generate one or more data signals representative of an amount of solids in the conduit. The control system includes a data acquisition system in communication with the sensors and a controller in communication with the data acquisition system. The data acquisition system receives the data signals and the controller generates the control signals. The controller is in communication with one or more valves positioned in the chemical loop. The valves are configured to regulate a flow of the solids through the chemical loop.
Coordinated joint motion control system with position error correction
Danko, George [Reno, NV
2011-11-22
Disclosed are an articulated hydraulic machine supporting, control system and control method for same. The articulated hydraulic machine has an end effector for performing useful work. The control system is capable of controlling the end effector for automated movement along a preselected trajectory. The control system has a position error correction system to correct discrepancies between an actual end effector trajectory and a desired end effector trajectory. The correction system can employ one or more absolute position signals provided by one or more acceleration sensors supported by one or more movable machine elements. Good trajectory positioning and repeatability can be obtained. A two-joystick controller system is enabled, which can in some cases facilitate the operator's task and enhance their work quality and productivity.
Coordinated joint motion control system with position error correction
Danko, George L.
2016-04-05
Disclosed are an articulated hydraulic machine supporting, control system and control method for same. The articulated hydraulic machine has an end effector for performing useful work. The control system is capable of controlling the end effector for automated movement along a preselected trajectory. The control system has a position error correction system to correct discrepancies between an actual end effector trajectory and a desired end effector trajectory. The correction system can employ one or more absolute position signals provided by one or more acceleration sensors supported by one or more movable machine elements. Good trajectory positioning and repeatability can be obtained. A two joystick controller system is enabled, which can in some cases facilitate the operator's task and enhance their work quality and productivity.
The semiotics of control and modeling relations in complex systems.
Joslyn, C
2001-01-01
We provide a conceptual analysis of ideas and principles from the systems theory discourse which underlie Pattee's semantic or semiotic closure, which is itself foundational for a school of theoretical biology derived from systems theory and cybernetics, and is now being related to biological semiotics and explicated in the relational biological school of Rashevsky and Rosen. Atomic control systems and models are described as the canonical forms of semiotic organization, sharing measurement relations, but differing topologically in that control systems are circularly and models linearly related to their environments. Computation in control systems is introduced, motivating hierarchical decomposition, hybrid modeling and control systems, and anticipatory or model-based control. The semiotic relations in complex control systems are described in terms of relational constraints, and rules and laws are distinguished as contingent and necessary functional entailments, respectively. Finally, selection as a meta-level of constraint is introduced as the necessary condition for semantic relations in control systems and models.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Passerini, Stefano; Ponciroli, Roberto; Vilim, Richard B.
Here, the interaction of the active control system with passive safety behavior is investigated for sodium-cooled fast reactors. A claim often made of advanced reactors is that they are passively safe against unprotected upset events. In practice, such upset events are not analyzed in the context of the plant control system, but rather the analyses are performed without considering the normally programmed response of the control system (open-loop approach). This represents an oversimplification of the safety case. The issue of passive safety override arises since the control system commands actuators whose motions have safety consequences. Depending on the upset involvingmore » the control system ( operator error, active control system failure, or inadvertent control system override), an actuator does not necessarily go in the same direction as needed for safety. So neglecting to account for control system action during an unprotected upset is nonconservative from a safety standpoint. It is important then, during the design of the plant, to consider the potential for the control system to work against the inherent and safe regulating effects of purposefully engineered temperature feedbacks.« less
NASA Astrophysics Data System (ADS)
Yudhi Irwanto, Herma
2018-02-01
The development of autonomous controller system that is specially used in our high speed UAV, it’s call RKX-200EDF/TJ controlled vehicle needs to be continued as a step to mastery and to developt control system of LAPAN’s satellite launching rocket. The weakness of the existing control system in this high speed UAV needs to be repaired and replaced using the autonomous controller system. Conversion steps for ready-to-fly system involved controlling X tail fin, adjusting auto take off procedure by adding X axis sensor, procedure of way points reading and process of measuring distance and heading to the nearest way point, developing user-friendly ground station, and adding tools for safety landing. The development of this autonomous controller system also covered a real flying test in Pandanwangi, Lumajang in November 2016. Unfortunately, the flying test was not successful because the booster rocket was blown right after burning. However, the system could record the event and demonstrated that the controller system had worked according to plan.
CFAVC scheme for high frequency series resonant inverter-fed domestic induction heating system
NASA Astrophysics Data System (ADS)
Nagarajan, Booma; Reddy Sathi, Rama
2016-01-01
This article presents the investigations on the constant frequency asymmetric voltage cancellation control in the AC-AC resonant converter-fed domestic induction heating system. Conventional fixed frequency control techniques used in the high frequency converters lead to non-zero voltage switching operation and reduced output power. The proposed control technique produces higher output power than the conventional fixed-frequency control strategies. In this control technique, zero-voltage-switching operation is maintained during different duty cycle operation for reduction in the switching losses. Complete analysis of the induction heating power supply system with asymmetric voltage cancellation control is discussed in this article. Simulation and experimental study on constant frequency asymmetric voltage cancellation (CFAVC)-controlled full bridge series resonant inverter is performed. Time domain simulation results for the open and closed loop of the system are obtained using MATLAB simulation tool. The simulation results prove the control of voltage and power in a wide range. PID controller-based closed loop control system achieves the voltage regulation of the proposed system for the step change in load. Hardware implementation of the system under CFAVC control is done using the embedded controller. The simulation and experimental results validate the performance of the CFAVC control technique for series resonant-based induction cooking system.
Evolutionary game based control for biological systems with applications in drug delivery.
Li, Xiaobo; Lenaghan, Scott C; Zhang, Mingjun
2013-06-07
Control engineering and analysis of biological systems have become increasingly important for systems and synthetic biology. Unfortunately, no widely accepted control framework is currently available for these systems, especially at the cell and molecular levels. This is partially due to the lack of appropriate mathematical models to describe the unique dynamics of biological systems, and the lack of implementation techniques, such as ultra-fast and ultra-small devices and corresponding control algorithms. This paper proposes a control framework for biological systems subject to dynamics that exhibit adaptive behavior under evolutionary pressures. The control framework was formulated based on evolutionary game based modeling, which integrates both the internal dynamics and the population dynamics. In the proposed control framework, the adaptive behavior was characterized as an internal dynamic, and the external environment was regarded as an external control input. The proposed open-interface control framework can be integrated with additional control algorithms for control of biological systems. To demonstrate the effectiveness of the proposed framework, an optimal control strategy was developed and validated for drug delivery using the pathogen Giardia lamblia as a test case. In principle, the proposed control framework can be applied to any biological system exhibiting adaptive behavior under evolutionary pressures. Copyright © 2013 Elsevier Ltd. All rights reserved.
Dynamic analysis of space robot remote control system
NASA Astrophysics Data System (ADS)
Kulakov, Felix; Alferov, Gennady; Sokolov, Boris; Gorovenko, Polina; Sharlay, Artem
2018-05-01
The article presents analysis on construction of two-stage remote control for space robots. This control ensures efficiency of the robot control system at large delays in transmission of control signals from the ground control center to the local control system of the space robot. The conditions for control stability of and high transparency are found.
46 CFR 58.30-50 - Requirements for miscellaneous fluid power and control systems.
Code of Federal Regulations, 2010 CFR
2010-10-01
...) MARINE ENGINEERING MAIN AND AUXILIARY MACHINERY AND RELATED SYSTEMS Fluid Power and Control Systems § 58.30-50 Requirements for miscellaneous fluid power and control systems. (a) All fluid power and control... 46 Shipping 2 2010-10-01 2010-10-01 false Requirements for miscellaneous fluid power and control...
46 CFR 58.30-50 - Requirements for miscellaneous fluid power and control systems.
Code of Federal Regulations, 2014 CFR
2014-10-01
...) MARINE ENGINEERING MAIN AND AUXILIARY MACHINERY AND RELATED SYSTEMS Fluid Power and Control Systems § 58.30-50 Requirements for miscellaneous fluid power and control systems. (a) All fluid power and control... 46 Shipping 2 2014-10-01 2014-10-01 false Requirements for miscellaneous fluid power and control...
21 CFR 870.3535 - Intra-aortic balloon and control system.
Code of Federal Regulations, 2014 CFR
2014-04-01
... syndrome, cardiac and non-cardiac surgery, or complications of heart failure. The special controls for this... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Intra-aortic balloon and control system. 870.3535... balloon and control system. (a) Identification. An intra-aortic balloon and control system is a...
46 CFR 58.30-50 - Requirements for miscellaneous fluid power and control systems.
Code of Federal Regulations, 2013 CFR
2013-10-01
...) MARINE ENGINEERING MAIN AND AUXILIARY MACHINERY AND RELATED SYSTEMS Fluid Power and Control Systems § 58.30-50 Requirements for miscellaneous fluid power and control systems. (a) All fluid power and control... 46 Shipping 2 2013-10-01 2013-10-01 false Requirements for miscellaneous fluid power and control...
46 CFR 58.30-50 - Requirements for miscellaneous fluid power and control systems.
Code of Federal Regulations, 2011 CFR
2011-10-01
...) MARINE ENGINEERING MAIN AND AUXILIARY MACHINERY AND RELATED SYSTEMS Fluid Power and Control Systems § 58.30-50 Requirements for miscellaneous fluid power and control systems. (a) All fluid power and control... 46 Shipping 2 2011-10-01 2011-10-01 false Requirements for miscellaneous fluid power and control...
46 CFR 58.30-50 - Requirements for miscellaneous fluid power and control systems.
Code of Federal Regulations, 2012 CFR
2012-10-01
...) MARINE ENGINEERING MAIN AND AUXILIARY MACHINERY AND RELATED SYSTEMS Fluid Power and Control Systems § 58.30-50 Requirements for miscellaneous fluid power and control systems. (a) All fluid power and control... 46 Shipping 2 2012-10-01 2012-10-01 false Requirements for miscellaneous fluid power and control...
Lam, H K
2012-02-01
This paper investigates the stability of sampled-data output-feedback (SDOF) polynomial-fuzzy-model-based control systems. Representing the nonlinear plant using a polynomial fuzzy model, an SDOF fuzzy controller is proposed to perform the control process using the system output information. As only the system output is available for feedback compensation, it is more challenging for the controller design and system analysis compared to the full-state-feedback case. Furthermore, because of the sampling activity, the control signal is kept constant by the zero-order hold during the sampling period, which complicates the system dynamics and makes the stability analysis more difficult. In this paper, two cases of SDOF fuzzy controllers, which either share the same number of fuzzy rules or not, are considered. The system stability is investigated based on the Lyapunov stability theory using the sum-of-squares (SOS) approach. SOS-based stability conditions are obtained to guarantee the system stability and synthesize the SDOF fuzzy controller. Simulation examples are given to demonstrate the merits of the proposed SDOF fuzzy control approach.
Neural-network hybrid control for antilock braking systems.
Lin, Chih-Min; Hsu, C F
2003-01-01
The antilock braking systems are designed to maximize wheel traction by preventing the wheels from locking during braking, while also maintaining adequate vehicle steerability; however, the performance is often degraded under harsh road conditions. In this paper, a hybrid control system with a recurrent neural network (RNN) observer is developed for antilock braking systems. This hybrid control system is comprised of an ideal controller and a compensation controller. The ideal controller, containing an RNN uncertainty observer, is the principal controller; and the compensation controller is a compensator for the difference between the system uncertainty and the estimated uncertainty. Since for dynamic response the RNN has capabilities superior to the feedforward NN, it is utilized for the uncertainty observer. The Taylor linearization technique is employed to increase the learning ability of the RNN. In addition, the on-line parameter adaptation laws are derived based on a Lyapunov function, so the stability of the system can be guaranteed. Simulations are performed to demonstrate the effectiveness of the proposed NN hybrid control system for antilock braking control under various road conditions.
A reusable rocket engine intelligen control
NASA Technical Reports Server (NTRS)
Merrill, Walter C.; Lorenzo, Carl F.
1988-01-01
An intelligent control system for reusable space propulsion systems for future launch vehicles is described. The system description includes a framework for the design. The framework consists of an execution level with high-speed control and diagnostics, and a coordination level which marries expert system concepts with traditional control. A comparison is made between air breathing and rocket engine control concepts to assess the relative levels of development and to determine the applicability of air breathing control concepts to future reusable rocket engine systems.
A reusable rocket engine intelligent control
NASA Technical Reports Server (NTRS)
Merrill, Walter C.; Lorenzo, Carl F.
1988-01-01
An intelligent control system for reusable space propulsion systems for future launch vehicles is described. The system description includes a framework for the design. The framework consists of an execution level with high-speed control and diagnostics, and a coordination level which marries expert system concepts with traditional control. A comparison is made between air breathing and rocket engine control concepts to assess the relative levels of development and to determine the applicability of air breathing control concepts ot future reusable rocket engine systems.
Seasat-A attitude control system
NASA Technical Reports Server (NTRS)
Weiss, R.; Rodden, J. J.; Hendricks, R. J.
1977-01-01
The Seasat-A attitude control system controls the attitude of the satellite system during injection into final circular orbit after Atlas boost, during orbit adjust and trim phases, and throughout the 3-year mission. Ascent and injection guidance and attitude control are provided by the Agena spacecraft with a gyrocompassed mass expulsion system. On-orbit attitude control functions are performed by a system that has its functional roots in the gravity-gradient momentum bias technology. The paper discusses hardware, control laws, and simulation results.
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.
The frontoparietal control system: A central role in mental health
Cole, Michael W.; Repovs, Grega; Anticevic, Alan
2014-01-01
Recent findings suggest the existence of a frontoparietal control system consisting of ‘flexible hubs’ that regulate distributed systems (e.g., visual, limbic, motor) according to current task goals. A growing number of studies are reporting alterations of this control system across a striking range of mental diseases. We suggest this may reflect a critical role for the control system in promoting and maintaining mental health. Specifically, we propose that this system implements feedback control to regulate symptoms as they arise (e.g., excessive anxiety reduced via regulation of amygdala), such that an intact control system is protective against a variety of mental illnesses. Consistent with this possibility, recent results indicate that several major mental illnesses involve altered brain-wide connectivity of the control system, likely altering its ability to regulate symptoms. These results suggest that this ‘immune system of the mind’ may be an especially important target for future basic and clinical research. PMID:24622818
Robust fast controller design via nonlinear fractional differential equations.
Zhou, Xi; Wei, Yiheng; Liang, Shu; Wang, Yong
2017-07-01
A new method for linear system controller design is proposed whereby the closed-loop system achieves both robustness and fast response. The robustness performance considered here means the damping ratio of closed-loop system can keep its desired value under system parameter perturbation, while the fast response, represented by rise time of system output, can be improved by tuning the controller parameter. We exploit techniques from both the nonlinear systems control and the fractional order systems control to derive a novel nonlinear fractional order controller. For theoretical analysis of the closed-loop system performance, two comparison theorems are developed for a class of fractional differential equations. Moreover, the rise time of the closed-loop system can be estimated, which facilitates our controller design to satisfy the fast response performance and maintain the robustness. Finally, numerical examples are given to illustrate the effectiveness of our methods. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.
Application of programmable logic controllers to space simulation
NASA Technical Reports Server (NTRS)
Sushon, Janet
1992-01-01
Incorporating a state-of-the-art process control and instrumentation system into a complex system for thermal vacuum testing is discussed. The challenge was to connect several independent control systems provided by various vendors to a supervisory computer. This combination will sequentially control and monitor the process, collect the data, and transmit it to color a graphic system for subsequent manipulation. The vacuum system upgrade included: replacement of seventeen diffusion pumps with eight cryogenic pumps and one turbomolecular pump, replacing a relay based control system, replacing vacuum instrumentation, and upgrading the data acquisition system.
Comparative study between two different active flutter suppression systems
NASA Technical Reports Server (NTRS)
Nissim, E.
1978-01-01
An activated leading-edge (LE)-tailing-edge (TE) control system is applied to a drone aircraft with the objective of enabling the drone to fly subsonically at dynamic pressures which are 44% above the open-loop flutter dynamic pressure. The control synthesis approach is based on the aerodynamic energy concept and it incorporates recent developments in this area. A comparison is made between the performance of the activated LE-TE control system and the performance of a TE control system, analyzed in a previous work. The results obtained indicate that although all the control systems achieve the flutter suppression objectives, the TE control system appears to be somewhat superior to the LE-TE control system, in this specific application. This superiority is manifested through reduced values of control surface activity over a wide range of flight conditions.
Thermal Vacuum Control Systems Options for Test Facilities
NASA Technical Reports Server (NTRS)
Marchetti, John
2008-01-01
This presentation suggests several Thermal Vacuum System (TVAC) control design approach methods for TVAC facilities. Over the past several years many aerospace companies have or are currently upgrading their TVAC testing facilities whether it be by upgrading old equipment or purchasing new. In doing so they are updating vacuum pumping and thermal capabilities of their chambers as well as their control systems. Although control systems are sometimes are considered second to the vacuum or thermal system upgrade process, they should not be taken lightly and must be planned and implemented with the equipment it is to control. Also, emphasis should be placed on how the operators will use the system as well as the requirements of "their" customers. Presented will be various successful methods of TVAC control systems from Programmable Logic Controller (PLC) based to personal computer (PC) based control.
Testing of a controller for a hybrid capillary pumped loop thermal control system
NASA Technical Reports Server (NTRS)
Schweickart, Russell; Ottenstein, Laura; Cullimore, Brent; Egan, Curtis; Wolf, Dave
1989-01-01
A controller for a series hybrid capillary pumped loop (CPL) system that requires no moving parts does not resrict fluid flow has been tested and has demonstrated improved performance characteristics over a plain CPL system and simple hybrid CPL systems. These include heat load sharing, phase separation, self-regulated flow control and distribution, all independent of most system pressure drop. In addition, the controlled system demonstrated a greater heat transport capability than the simple CPL system but without the large fluid inventory requirement of the hybrid systems. A description of the testing is presented along with data that show the advantages of the system.
Concept report: Microprocessor control of electrical power system
NASA Technical Reports Server (NTRS)
Perry, E.
1977-01-01
An electrical power system which uses a microprocessor for systems control and monitoring is described. The microprocessor controlled system permits real time modification of system parameters for optimizing a system configuration, especially in the event of an anomaly. By reducing the components count, the assembling and testing of the unit is simplified, and reliability is increased. A resuable modular power conversion system capable of satisfying a large percentage of space applications requirements is examined along with the programmable power processor. The PC global controller which handles systems control and external communication is analyzed, and a software description is given. A systems application summary is also included.
Non-predictor control of a class of feedforward nonlinear systems with unknown time-varying delays
NASA Astrophysics Data System (ADS)
Koo, Min-Sung; Choi, Ho-Lim
2016-08-01
This paper generalises the several recent results on the control of feedforward time-delay nonlinear systems. First, in view of system formulation, there are unknown time-varying delays in both states and main control input. Also, the considered nonlinear system has extended feedforward nonlinearities. Second, in view of control solution, our proposed controller is a non-predictor feedback controller whereas smith-predictor type controllers are used in the several existing results. Moreover, our controller does not need any information on the unknown delays except their upper bounds. Thus, our result has certain merits in both system formulation and control solution perspective. The analysis and example are given for clear illustration.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Passerini, Stefano; Ponciroli, Roberto; Vilim, Richard B.
Here, the interaction of the active control system with passive safety behavior is investigated for sodium-cooled fast reactors. A claim often made of advanced reactors is that they are passively safe against unprotected upset events. In practice, such upset events are not analyzed in the context of the plant control system, but rather the analyses are performed without considering the normally programmed response of the control system (open-loop approach). This represents an oversimplification of the safety case. The issue of passive safety override arises since the control system commands actuators whose motions have safety consequences. Depending on the upset involvingmore » the control system ( operator error, active control system failure, or inadvertent control system override), an actuator does not necessarily go in the same direction as needed for safety. So neglecting to account for control system action during an unprotected upset is nonconservative from a safety standpoint. It is important then, during the design of the plant, to consider the potential for the control system to work against the inherent and safe regulating effects of purposefully engineered temperature feedbacks.« less
Passerini, Stefano; Ponciroli, Roberto; Vilim, Richard B.
2017-06-21
Here, the interaction of the active control system with passive safety behavior is investigated for sodium-cooled fast reactors. A claim often made of advanced reactors is that they are passively safe against unprotected upset events. In practice, such upset events are not analyzed in the context of the plant control system, but rather the analyses are performed without considering the normally programmed response of the control system (open-loop approach). This represents an oversimplification of the safety case. The issue of passive safety override arises since the control system commands actuators whose motions have safety consequences. Depending on the upset involvingmore » the control system ( operator error, active control system failure, or inadvertent control system override), an actuator does not necessarily go in the same direction as needed for safety. So neglecting to account for control system action during an unprotected upset is nonconservative from a safety standpoint. It is important then, during the design of the plant, to consider the potential for the control system to work against the inherent and safe regulating effects of purposefully engineered temperature feedbacks.« less
NASA Technical Reports Server (NTRS)
Young, G.
1982-01-01
A design methodology capable of dealing with nonlinear systems, such as a controlled ecological life support system (CELSS), containing parameter uncertainty is discussed. The methodology was applied to the design of discrete time nonlinear controllers. The nonlinear controllers can be used to control either linear or nonlinear systems. Several controller strategies are presented to illustrate the design procedure.
Propulsion system-flight control integration-flight evaluation and technology transition
NASA Technical Reports Server (NTRS)
Burcham, Frank W., Jr.; Gilyard, Glenn B.; Myers, Lawrence P.
1990-01-01
Integration of propulsion and flight control systems and their optimization offering significant performance improvement are assessed. In particular, research programs conducted by NASA on flight control systems and propulsion system-flight control interactions on the YF-12 and F-15 aircraft are addressed; these programs have demonstrated increased thrust, reduced fuel consumption, increased engine life, and improved aircraft performance. Focus is placed on altitude control, speed-Mach control, integrated controller design, as well as flight control systems and digital electronic engine control. A highly integrated digital electronic control program is analyzed and compared with a performance seeking control program. It is shown that the flight evaluation and demonstration of these technologies have been a key part in the transition of the concepts to production and operational use on a timely basis.
Advances in Thrust-Based Emergency Control of an Airplane
NASA Technical Reports Server (NTRS)
Creech, Gray; Burken, John J.; Burcham, Bill
2003-01-01
Engineers at NASA's Dryden Flight Research Center have received a patent on an emergency flight-control method implemented by a propulsion-controlled aircraft (PCA) system. Utilizing the preexisting auto-throttle and engine-pressure-ratio trim controls of the airplane, the PCA system provides pitch and roll control for landing an airplane safely without using aerodynamic control surfaces that have ceased to function because of a primary-flight-control-system failure. The installation of the PCA does not entail any changes in pre-existing engine hardware or software. [Aspects of the method and system at previous stages of development were reported in Thrust-Control System for Emergency Control of an Airplane (DRC-96-07), NASA Tech Briefs, Vol. 25, No. 3 (March 2001), page 68 and Emergency Landing Using Thrust Control and Shift of Weight (DRC-96-55), NASA Tech Briefs, Vol. 26, No. 5 (May 2002), page 58.]. Aircraft flight-control systems are designed with extensive redundancy to ensure low probabilities of failure. During recent years, however, several airplanes have exhibited major flight-control-system failures, leaving engine thrust as the last mode of flight control. In some of these emergency situations, engine thrusts were successfully modulated by the pilots to maintain flight paths or pitch angles, but in other situations, lateral control was also needed. In the majority of such control-system failures, crashes resulted and over 1,200 people died. The challenge lay in creating a means of sufficient degree of thrust-modulation control to safely fly and land a stricken airplane. A thrust-modulation control system designed for this purpose was flight-tested in a PCA an MD-11 airplane. The results of the flight test showed that without any operational control surfaces, a pilot can land a crippled airplane (U.S. Patent 5,330,131). The installation of the original PCA system entailed modifications not only of the flight-control computer (FCC) of the airplane but also of each engine-control computer. Inasmuch as engine-manufacturer warranties do not apply to modified engines, the challenge became one of creating a PCA system that does not entail modifications of the engine computers.
NASA Astrophysics Data System (ADS)
Abou-Elnour, Ali; Thabt, A.; Helmy, S.; Kashf, Y.; Hadad, Y.; Tarique, M.; Abo-Elnor, Ossama
2014-04-01
In the present work, wireless sensor network and smart real-time controlling and monitoring system are integrated for efficient energy management of standalone photovoltaic system. The proposed system has two main components namely the monitoring and controlling system and the wireless communication system. LabView software has been used in the implementation of the monitoring and controlling system. On the other hand, ZigBee wireless modules have been used to implement the wireless system. The main functions of monitoring and controlling unit is to efficiently control the energy consumption form the photovoltaic system based on accurate determination of the periods of times at which the loads are required to be operated. The wireless communication system send the data from the monitoring and controlling unit to the loads at which desired switching operations are performed. The wireless communication system also continuously feeds the monitoring and controlling unit with updated input data from the sensors and from the photovoltaic module send to calculate and record the generated, the consumed, and the stored energy to apply load switching saving schemes if necessary. It has to be mentioned that our proposed system is a low cost and low power system because and it is flexible to be upgraded to fulfill additional users' requirements.
Neural network based automatic limit prediction and avoidance system and method
NASA Technical Reports Server (NTRS)
Calise, Anthony J. (Inventor); Prasad, Jonnalagadda V. R. (Inventor); Horn, Joseph F. (Inventor)
2001-01-01
A method for performance envelope boundary cueing for a vehicle control system comprises the steps of formulating a prediction system for a neural network and training the neural network to predict values of limited parameters as a function of current control positions and current vehicle operating conditions. The method further comprises the steps of applying the neural network to the control system of the vehicle, where the vehicle has capability for measuring current control positions and current vehicle operating conditions. The neural network generates a map of current control positions and vehicle operating conditions versus the limited parameters in a pre-determined vehicle operating condition. The method estimates critical control deflections from the current control positions required to drive the vehicle to a performance envelope boundary. Finally, the method comprises the steps of communicating the critical control deflection to the vehicle control system; and driving the vehicle control system to provide a tactile cue to an operator of the vehicle as the control positions approach the critical control deflections.
Three degree-of-freedom force feedback control for robotic mating of umbilical lines
NASA Technical Reports Server (NTRS)
Fullmer, R. Rees
1988-01-01
The use of robotic manipulators for the mating and demating of umbilical fuel lines to the Space Shuttle Vehicle prior to launch is investigated. Force feedback control is necessary to minimize the contact forces which develop during mating. The objective is to develop and demonstrate a working robotic force control system. Initial experimental force control tests with an ASEA IRB-90 industrial robot using the system's Adaptive Control capabilities indicated that control stability would by a primary problem. An investigation of the ASEA system showed a 0.280 second software delay between force input commands and the output of command voltages to the servo system. This computational delay was identified as the primary cause of the instability. Tests on a second path into the ASEA's control computer using the MicroVax II supervisory computer show that time delay would be comparable, offering no stability improvement. An alternative approach was developed where the digital control system of the robot was disconnected and an analog electronic force controller was used to control the robot's servosystem directly, allowing the robot to use force feedback control while in rigid contact with a moving three-degree-of-freedom target. An alternative approach was developed where the digital control system of the robot was disconnected and an analog electronic force controller was used to control the robot's servo system directly. This method allowed the robot to use force feedback control while in rigid contact with moving three degree-of-freedom target. Tests on this approach indicated adequate force feedback control even under worst case conditions. A strategy to digitally-controlled vision system was developed. This requires switching between the digital controller when using vision control and the analog controller when using force control, depending on whether or not the mating plates are in contact.
Learning control system design based on 2-D theory - An application to parallel link manipulator
NASA Technical Reports Server (NTRS)
Geng, Z.; Carroll, R. L.; Lee, J. D.; Haynes, L. H.
1990-01-01
An approach to iterative learning control system design based on two-dimensional system theory is presented. A two-dimensional model for the iterative learning control system which reveals the connections between learning control systems and two-dimensional system theory is established. A learning control algorithm is proposed, and the convergence of learning using this algorithm is guaranteed by two-dimensional stability. The learning algorithm is applied successfully to the trajectory tracking control problem for a parallel link robot manipulator. The excellent performance of this learning algorithm is demonstrated by the computer simulation results.
A Combined Energy Management Algorithm for Wind Turbine/Battery Hybrid System
NASA Astrophysics Data System (ADS)
Altin, Necmi; Eyimaya, Süleyman Emre
2018-03-01
From an energy management standpoint, natural phenomena such as solar irradiation and wind speed are uncontrolled variables, so the correlation between the energy generated by renewable energy sources and energy demand cannot always be predicted. For this reason, energy storage systems are used to provide more efficient renewable energy systems. In these systems, energy management systems are used to control the energy storage system and establish a balance between the generated power and the power demand. In addition, especially in wind turbines, rapidly varying wind speeds cause wind power fluctuations, which threaten the power system stability, especially at high power levels. Energy storage systems are also used to mitigate the power fluctuations and sustain the power system's stability. In these systems, another controller which controls the energy storage system power to mitigate power fluctuations is required. These two controllers are different from each other. In this study, a combined energy management algorithm is proposed which can perform both as an energy control system and a power fluctuation mitigation system. The proposed controller is tested with wind energy conversion system modeled in MATLAB/Simulink. Simulation results show that the proposed controller acts as an energy management system while, at the same time, mitigating power fluctuations.
Systems and Methods for Collaboratively Controlling at Least One Aircraft
NASA Technical Reports Server (NTRS)
Estkowski, Regina I. (Inventor)
2016-01-01
An unmanned vehicle management system includes an unmanned aircraft system (UAS) control station controlling one or more unmanned vehicles (UV), a collaborative routing system, and a communication network connecting the UAS and the collaborative routing system. The collaborative routing system being configured to receive flight parameters from an operator of the UAS control station and, based on the received flight parameters, automatically present the UAS control station with flight plan options to enable the operator to operate the UV in a defined airspace.
NASA Astrophysics Data System (ADS)
Abramov, G. V.; Emeljanov, A. E.; Ivashin, A. L.
Theoretical bases for modeling a digital control system with information transfer via the channel of plural access and a regular quantization cycle are submitted. The theory of dynamic systems with random changes of the structure including elements of the Markov random processes theory is used for a mathematical description of a network control system. The characteristics of similar control systems are received. Experimental research of the given control systems is carried out.
NASA Astrophysics Data System (ADS)
Chen, Syuan-Yi; Gong, Sheng-Sian
2017-09-01
This study aims to develop an adaptive high-precision control system for controlling the speed of a vane-type air motor (VAM) pneumatic servo system. In practice, the rotor speed of a VAM depends on the input mass air flow, which can be controlled by the effective orifice area (EOA) of an electronic throttle valve (ETV). As the control variable of a second-order pneumatic system is the integral of the EOA, an observation-based adaptive dynamic sliding-mode control (ADSMC) system is proposed to derive the differential of the control variable, namely, the EOA control signal. In the ADSMC system, a proportional-integral-derivative fuzzy neural network (PIDFNN) observer is used to achieve an ideal dynamic sliding-mode control (DSMC), and a supervisor compensator is designed to eliminate the approximation error. As a result, the ADSMC incorporates the robustness of a DSMC and the online learning ability of a PIDFNN. To ensure the convergence of the tracking error, a Lyapunov-based analytical method is employed to obtain the adaptive algorithms required to tune the control parameters of the online ADSMC system. Finally, our experimental results demonstrate the precision and robustness of the ADSMC system for highly nonlinear and time-varying VAM pneumatic servo systems.
Chang, Yeong-Chan
2005-12-01
This paper addresses the problem of designing adaptive fuzzy-based (or neural network-based) robust controls for a large class of uncertain nonlinear time-varying systems. This class of systems can be perturbed by plant uncertainties, unmodeled perturbations, and external disturbances. Nonlinear H(infinity) control technique incorporated with adaptive control technique and VSC technique is employed to construct the intelligent robust stabilization controller such that an H(infinity) control is achieved. The problem of the robust tracking control design for uncertain robotic systems is employed to demonstrate the effectiveness of the developed robust stabilization control scheme. Therefore, an intelligent robust tracking controller for uncertain robotic systems in the presence of high-degree uncertainties can easily be implemented. Its solution requires only to solve a linear algebraic matrix inequality and a satisfactorily transient and asymptotical tracking performance is guaranteed. A simulation example is made to confirm the performance of the developed control algorithms.
Tandem robot control system and method for controlling mobile robots in tandem
Hayward, David R.; Buttz, James H.; Shirey, David L.
2002-01-01
A control system for controlling mobile robots provides a way to control mobile robots, connected in tandem with coupling devices, to navigate across difficult terrain or in closed spaces. The mobile robots can be controlled cooperatively as a coupled system in linked mode or controlled individually as separate robots.
National IVHS Architecture Development Strategy
DOT National Transportation Integrated Search
1994-01-27
NATIONAL INFORMATION AND CONTROL SYSTEMS ARE EMERGING THAT REQUIRE SYSTEM ARCHITECTURES FOR DEPLOYMENT ACROSS THE NATION, E.G., AIR TRAFFIC CONTROL SYSTEMS, MILITARY COMMAND AND CONTROL SYSTEMS, AND OTHER NATIONAL INFORMATION SYSTEMS. THE REQUIRED CH...
Towards autonomous fuzzy control
NASA Technical Reports Server (NTRS)
Shenoi, Sujeet; Ramer, Arthur
1993-01-01
The efficient implementation of on-line adaptation in real time is an important research problem in fuzzy control. The goal is to develop autonomous self-organizing controllers employing system-independent control meta-knowledge which enables them to adjust their control policies depending on the systems they control and the environments in which they operate. An autonomous fuzzy controller would continuously observe system behavior while implementing its control actions and would use the outcomes of these actions to refine its control policy. It could be designed to lie dormant when its control actions give rise to adequate performance characteristics but could rapidly and autonomously initiate real-time adaptation whenever its performance degrades. Such an autonomous fuzzy controller would have immense practical value. It could accommodate individual variations in system characteristics and also compensate for degradations in system characteristics caused by wear and tear. It could also potentially deal with black-box systems and control scenarios. On-going research in autonomous fuzzy control is reported. The ultimate research objective is to develop robust and relatively inexpensive autonomous fuzzy control hardware suitable for use in real time environments.
Systems, methods, and products for graphically illustrating and controlling a droplet actuator
NASA Technical Reports Server (NTRS)
Brafford, Keith R. (Inventor); Pamula, Vamsee K. (Inventor); Paik, Philip Y. (Inventor); Pollack, Michael G. (Inventor); Sturmer, Ryan A. (Inventor); Smith, Gregory F. (Inventor)
2010-01-01
Systems for controlling a droplet microactuator are provided. According to one embodiment, a system is provided and includes a controller, a droplet microactuator electronically coupled to the controller, and a display device displaying a user interface electronically coupled to the controller, wherein the system is programmed and configured to permit a user to effect a droplet manipulation by interacting with the user interface. According to another embodiment, a system is provided and includes a processor, a display device electronically coupled to the processor, and software loaded and/or stored in a storage device electronically coupled to the controller, a memory device electronically coupled to the controller, and/or the controller and programmed to display an interactive map of a droplet microactuator. According to yet another embodiment, a system is provided and includes a controller, a droplet microactuator electronically coupled to the controller, a display device displaying a user interface electronically coupled to the controller, and software for executing a protocol loaded and/or stored in a storage device electronically coupled to the controller, a memory device electronically coupled to the controller, and/or the controller.