scholarly journals p54nrb/NONO Regulates Cyclic AMP-Dependent Glucocorticoid Production by Modulating Phosphodiesterase mRNA Splicing and Degradation

2015 ◽  
Vol 35 (7) ◽  
pp. 1223-1237 ◽  
Author(s):  
Jia Yang Lu ◽  
Marion B. Sewer
Keyword(s):  
Cyclic Amp ◽  
Nuclear Protein ◽  
Intracellular Camp ◽  
Acth Stimulation ◽  
Content Type ◽  
Control Gene Expression ◽  
Rna Export ◽  
The Stability ◽  
Glucocorticoid Production ◽  
Nuclear Processes

Glucocorticoid production in the adrenal cortex is activated in response to an increase in cyclic AMP (cAMP) signaling. The nuclear protein p54nrb/NONO belongs to theDrosophilabehavior/human splicing (DBHS) family and has been implicated in several nuclear processes, including transcription, splicing, and RNA export. We previously identified p54nrb/NONO as a component of a protein complex that regulates the transcription of CYP17A1, a gene required for glucocorticoid production. Based on the multiple mechanisms by which p54nrb/NONO has been shown to control gene expression and the ability of the protein to be recruited to the CYP17A1 promoter, we sought to further define the molecular mechanism by which p54nrb/NONO confers optimal cortisol production. We show here that silencing p54nrb/NONO expression in H295R human adrenocortical cells decreases the ability of the cells to increase intracellular cAMP production and subsequent cortisol biosynthesis in response to adrenocorticotropin hormone (ACTH) stimulation. Interestingly, the expression of multiple phosphodiesterase (PDE) isoforms, including PDE2A, PDE3A, PDE3B, PDE4A, PDE4D, and PDE11A, was induced in p54nrb/NONO knockdown cells. Investigation of the mechanism by which silencing of p54nrb/NONO led to increased expression of select PDE isoforms revealed that p54nrb/NONO regulates the splicing of a subset of PDE isoforms. Importantly, we also identify a role for p54nrb/NONO in regulating the stability of PDE transcripts by facilitating the interaction between the exoribonuclease XRN2 and select PDE transcripts. In summary, we report that p54nrb/NONO modulates cAMP-dependent signaling, and ultimately cAMP-stimulated glucocorticoid biosynthesis by regulating the splicing and degradation of PDE transcripts.

Effect of Cyclic AMP and Cyclic GMP on Thromboplastin (Factor III) Synthesis in Human Monocytes In Vitro

1983 ◽  
Vol 50 (04) ◽  
pp. 804-809 ◽  
Author(s):  
Torstein Lyberg
Keyword(s):  
Cyclic Amp ◽  
Cyclic Gmp ◽  
Immune Complexes ◽  
Phosphodiesterase Inhibitors ◽  
Inhibitory Effect ◽  
Intracellular Camp ◽  
Human Monocytes ◽  
Purified Protein Derivative ◽  
A 23187

SummaryHuman monocytes in vitro respond to various agents (immune complexes, lectins, endotoxin, the divalent ionophore A 23187, 12-0-tetradecanoyl-phorbol 13-acetate [TPA], purified protein derivative [PPD] of Bacille Calmette-Guerin) with an increased synthesis of the protein component of thromboplastin. The effect of cyclic AMP and cyclic GMP on this response has been studied. Dibutyryl-cyclic AMP, prostaglandin E1 and the phosphodiesterase inhibitors 3-butyl-1-methyl-xanthine (MIX) and rac -4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 201724), separately and in combination have a pronounced inhibitory effect on the response to immune complexes and PPD, and a moderate effect on the response to endotoxin and lectins. The effect on TPA response and on the response to A 23187 was slight. Dibutyryl-cyclic GMP (1 mM) gave a slight inhibition of the TPA arid IC response, but had essentially no effect on the response to other inducers. The intracellular cAMP level increased when monocytes were incubated with IC, TPA or A 23187 followed by a decrease to basal levels within 1-2 hr, whereas lectin (PHA) and PPD did not induce such changes. The cAMP response to endotoxin varied. Stimulation with IC induced an increase in monocyte cGMP levels, whereas the other stimulants did not cause such changes.

Fusion based learning approach for predicting concrete pouring productivity based on construction and supply parameters

2016 ◽  
Vol 16 (2) ◽  
pp. 185-202 ◽  
Author(s):  
Mojtaba Maghrebi ◽  
Ali Shamsoddini ◽  
S. Travis Waller
Keyword(s):  
Supply Chain ◽  
Production Rate ◽  
Learning Method ◽  
Data Set ◽  
Content Type ◽  
Field Database ◽  
The Stability ◽  
Stable Learning ◽  
Ready Mixed Concrete ◽  
Practical Implications

Purpose The purpose of this paper is to predict the concrete pouring production rate by considering both construction and supply parameters, and by using a more stable learning method. Design/methodology/approach Unlike similar approaches, this paper considers not only construction site parameters, but also supply chain parameters. Machine learner fusion-regression (MLF-R) is used to predict the production rate of concrete pouring tasks. Findings MLF-R is used on a field database including 2,600 deliveries to 507 different locations. The proposed data set and the results are compared with ANN-Gaussian, ANN-Sigmoid and Adaboost.R2 (ANN-Gaussian). The results show better performance of MLF-R obtaining the least root mean square error (RMSE) compared with other methods. Moreover, the RMSEs derived from the predictions by MLF-R in some trials had the least standard deviation, indicating the stability of this approach among similar used approaches. Practical implications The size of the database used in this study is much larger than the size of databases used in previous studies. It helps authors draw their conclusions more confidently and introduce more generalised models that can be used in the ready-mixed concrete industry. Originality/value Introducing a more stable learning method for predicting the concrete pouring production rate helps not only construction parameters, but also traffic and supply chain parameters.

scholarly journals Coxiella burnetii Alters Cyclic AMP-Dependent Protein Kinase Signaling during Growth in Macrophages

2012 ◽  
Vol 80 (6) ◽  
pp. 1980-1986 ◽  
Author(s):  
Laura J. MacDonald ◽  
Richard C. Kurten ◽  
Daniel E. Voth
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Coxiella Burnetii ◽  
Alveolar Macrophages ◽  
Q Fever ◽  
Parasitophorous Vacuole ◽  
Dependent Protein Kinase ◽  
Content Type ◽  
Bacterial Agent ◽  
Dependent Protein

ABSTRACTCoxiella burnetiiis the bacterial agent of human Q fever, an acute, flu-like illness that can present as chronic endocarditis in immunocompromised individuals. Following aerosol-mediated transmission,C. burnetiireplicates in alveolar macrophages in a unique phagolysosome-like parasitophorous vacuole (PV) required for survival. The mechanisms ofC. burnetiiintracellular survival are poorly defined and a recent Q fever outbreak in the Netherlands emphasizes the need for better understanding this unique host-pathogen interaction. We recently demonstrated that inhibition of host cyclic AMP-dependent protein kinase (PKA) activity negatively impacts PV formation. In the current study, we confirmed PKA involvement in PV biogenesis and probed the role of PKA signaling duringC. burnetiiinfection of macrophages. Using PKA-specific inhibitors, we found the kinase was needed for biogenesis of prototypical PV andC. burnetiireplication. PKA and downstream targets were differentially phosphorylated throughout infection, suggesting prolonged regulation of the pathway. Importantly, the pathogen actively triggered PKA activation, which was also required for PV formation by virulentC. burnetiiisolates during infection of primary human alveolar macrophages. A subset of PKA-specific substrates were differentially phosphorylated duringC. burnetiiinfection, suggesting the pathogen uses PKA signaling to control distinct host cell responses. Collectively, the current results suggest a versatile role for PKA inC. burnetiiinfection and indicate virulent organisms usurp host kinase cascades for efficient intracellular growth.

Investigation of sustainability of lubricated journal bearing under relevant design parameters

2018 ◽  
Vol 70 (4) ◽  
pp. 789-804 ◽  
Author(s):  
M.M. Shahin ◽  
Mohammad Asaduzzaman Chowdhury ◽  
Md. Arefin Kowser ◽  
Uttam Kumar Debnath ◽  
M.H. Monir
Keyword(s):  
Aspect Ratio ◽  
Elastic Strain ◽  
Journal Bearing ◽  
Design Parameters ◽  
Content Type ◽  
Computational Fluid Dynamics Cfd ◽  
Stress Formation ◽  
Bearing Design ◽  
The Stability ◽  
Bearing Friction

Purpose The purposes of the present study are to ensure higher sustainability of journal bearings under different applied loads and to observe bearing performances such as elastic strain, total deformation and stress formation. Design/methodology/approach A journal bearing test rig was used to determine the effect of the applied load on the bearing friction, film thickness, lubricant film pressure, etc. A steady-state analysis was performed to obtain the bearing performance. Findings An efficient aspect ratio (L/D) range was obtained to increase the durability or the stability of the bearing while the bearing is in the working condition by using SAE 5W-30 oil. The results from the study were compared with previous studies in which different types of oil and water, such as Newtonian fluid (NF), magnetorheological fluid (MRF) and nonmagnetorheological fluid (NMRF), were used as the lubricant. To ensure a preferable aspect ratio range (0.25-0.50), a computational fluid dynamics (CFD) analysis was conducted by ANSYS; the results show a lower elastic strain and deformation within the preferable aspect ratio (0.25-0.50) rather than a higher aspect ratio using the SAE 5W-30 oil. Originality/value It is expected that the findings of this study will contribute to the improvement of the bearing design and the bearing lubricating system.

Analysis of Hiemenz flow of Reiner-Rivlin fluid over a stretching/shrinking sheet

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Golam Mortuja Sarkar ◽  
Suman Sarkar ◽  
Bikash Sahoo
Keyword(s):  
Nusselt Number ◽  
Stability Analysis ◽  
Friction Coefficient ◽  
Skin Friction Coefficient ◽  
Dual Solutions ◽  
Shrinking Sheet ◽  
Content Type ◽  
Hiemenz Flow ◽  
Self Similar ◽  
The Stability

Purpose This paper aims to theoretically and numerically investigate the steady two-dimensional (2D) Hiemenz flow with heat transfer of Reiner-Rivlin fluid over a linearly stretching/shrinking sheet. Design/methodology/approach The Navier–Stokes equations are transformed into self-similar equations using appropriate similarity transformations and then solved numerically by using shooting technique. A simple but effective mathematical analysis has been used to prove the existence of a solution for stretching case (λ> 0). Moreover, an attempt has been laid to carry the asymptotic solution behavior for large stretching. The obtained asymptotic solutions are compared with direct numerical solutions, and the comparison is quite remarkable. Findings It is observed that the self-similar equations exhibit dual solutions within the range [λc, −1] of shrinking parameter λ, where λc is the turning point from where the dual solutions bifurcate. Unique solution is found for all stretching case (λ > 0). It is noticed that the effects of cross-viscous parameter L and shrinking parameter λ on velocity and thermal fields show opposite character in the dual solution branches. Thus, a linear temporal stability analysis is performed to determine the basic feasible solution. The stability analysis is based on the sign of the smallest eigenvalue, where positive or negative sign leading to a stable or unstable solution. The stability analysis reveals that the first solution is stable that describes the main flow. Increase in cross-viscous parameter L resulting in a significant increment in skin friction coefficient, local Nusselt number and dual solutions domain. Originality/value This work’s originality is to examine the combined effects of cross-viscous parameter and stretching/shrinking parameter on skin friction coefficient, local Nusselt number, velocity and temperature profiles of Hiemenz flow over a stretching/shrinking sheet. Although many studies on viscous fluid and nanofluid have been investigated in this field, there are still limited discoveries on non-Newtonian fluids. The obtained results can be used as a benchmark for future studies of higher-grade non-Newtonian flows with several physical aspects. All the generated results are claimed to be novel and have not been published elsewhere.

Robust active disturbance attenuation control of an uncertain quadrotor

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Nigar Ahmed ◽  
Ajeet kumar Bhatia ◽  
Syed Awais Ali Shah
Keyword(s):  
Control Algorithm ◽  
Sliding Mode ◽  
The State ◽  
Disturbance Attenuation ◽  
State Variables ◽  
Pass Filter ◽  
Low Pass Filter ◽  
Content Type ◽  
Highly Nonlinear ◽  
The Stability

PurposeThe aim of this research is to design a robust active disturbance attenuation control (RADAC) technique combined with an extended high gain observer (EHGO) and low pass filter (LPF).Design/methodology/approachFor designing a RADAC technique, the sliding mode control (SMC) method is used. Since the standard method of SMC exhibits a chattering phenomenon in the controller, a multilayer sliding mode surface is designed for avoiding the chattering. In addition, to attenuate the unwanted uncertainties and disturbances (UUDs), the techniques of EHGO and LPF are deployed. Besides acting as a patch for disturbance attenuation, the EHGO design estimates the state variables. To investigate the stability and effectiveness of the designed control algorithm, the stability analysis followed by the simulation study is presented.FindingsThe major findings include the design of a chattering-free RADAC controller based on the multilayer sliding mode surface. Furthermore, a criterion of integrating the LPF scheme within the EHGO scheme is also developed to attenuate matched and mismatched UUDs.Practical implicationsIn practice, the quadrotor flight is opposed by different kinds of the UUDs. And, the model of the quadrotor is a highly nonlinear underactuated model. Thus, the dynamics of the quadrotor model become more complex and uncertain due to the additional UUDs. Hence, it is necessary to design a robust disturbance attenuation technique with the ability to estimate the state variables and attenuate the UUDs and also achieve the desired control objectives.Originality/valueDesigning control methods to attenuate the disturbances while assuming that the state variables are known is a common practice. However, investigating the uncertain plants with unknown states along with the disturbances is rarely taken in consideration for the control design. Hence, this paper presents a control algorithm to address the issues of the UUDs as well as investigate a criterion to reduce the chattering incurred in the controller due to the standard SMC algorithm.

Constant force control for aluminum wheel hub grinding based on ESO + backstepping

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Shijie Dai ◽  
Yufeng Zhao ◽  
Wenbin Ji ◽  
Jiaheng Mu ◽  
Fengbao Hu
Keyword(s):  
Control Strategy ◽  
Force Control ◽  
Control Method ◽  
Response Speed ◽  
Backstepping Control ◽  
Constant Force ◽  
Content Type ◽  
Disturbance Rejection Control ◽  
The Stability ◽  
Differential Control

Purpose This paper aims to present a control method to realize the constant force grinding of automobile wheel hub. Design/methodology/approach A constant force control strategy combined by extended state observer (ESO) and backstepping control is proposed. ESO is used to estimate the total disturbance to improve the anti-interference and stability of the system and Backstepping control is used to improve the response speed of the system. Findings The simulation and grinding experimental results show that, compared with the proportional integral differential control and active disturbance rejection control, the designed controller can improve the dynamic response performance and anti-interference ability of the system and can quickly track the expected force and improve the grinding quality of the hub surface. Originality/value The main contribution of this paper lies in the proposed of a new constant force control strategy, which significantly improved the stability and precision of grinding force.

Pharmacological characterization of cyclic AMP receptors mediating gene regulation in Dictyostelium discoideum

1986 ◽  
Vol 6 (7) ◽  
pp. 2402-2408
Author(s):  
B Haribabu ◽  
R P Dottin
Keyword(s):  
Gene Expression ◽  
Cyclic Amp ◽  
Cell Surface ◽  
Dictyostelium Discoideum ◽  
Cell Surface Receptor ◽  
Intracellular Camp ◽  
Response Curves ◽  
Pharmacological Characterization ◽  
Surface Receptor ◽  
Extracellular Molecules

Extracellular molecules regulate gene expression in eucaryotes. Exogenous cyclic AMP (cAMP) affects the expression of a large number of developmentally regulated genes in Dictyostelium discoideum. Here, we determine the specificity of the receptor(s) which mediates gene expression by using analogs of cAMP. The order of potency with which these analogs affect the expression of specific genes is consistent with the specificity of their binding to a cell surface receptor and is distinct from their affinity for intracellular cAMP-dependent protein kinase. Dose-response curves with cAMP and adenosine 3',5'-monophosphorothioate, a nonhydrolyzable analog, revealed that the requirement for high concentrations of exogenous cAMP for regulating gene expression is due to the rapid degradation of cAMP by phosphodiesterase. The addition of low concentrations of cAMP (100 nM) or analogs in pulses also regulates gene expression. Both the genes that are positively regulated by exogenous cAMP and the discoidin gene, which is negatively regulated, respond to cAMP analogs to the same degree. Genes expressed in prespore or prestalk cells are also similarly regulated. These data suggest that the effects are mediated through the same receptor. The specificity of this receptor is indistinguishable from that of the well-characterized cell surface cAMP receptor.

COO vs ROO: importance of the origin in customer preferences towards financial entities

2017 ◽  
Vol 34 (2) ◽  
pp. 206-223 ◽  
Author(s):  
José Manuel García-Gallego ◽  
Antonio Chamorro Mera
Keyword(s):  
Brand Management ◽  
Preference Structure ◽  
Content Type ◽  
Services Sector ◽  
Customer Preferences ◽  
Starting Point ◽  
Remarkable Result ◽  
Place Of Origin ◽  
Regional Brand ◽  
The Stability

Purpose The purpose of this paper is to determine the importance that customers give to the origin attribute when selecting a financial entity compared to other features directly related to the service that these institutions provide. In addition, this study aims at analysing what level of brand origin provides a greater utility for customers in their preference structure: regional, national or foreign. Design/methodology/approach The technique of conjoint analysis is applied via a survey of 427 customers to determine customers’ preference structure when choosing a financial entity. Findings Of particular note among the main results is the great importance the respondents give to the origin of the entity, preferring regional over national or foreign institutions. The existence of three different segments of customers based on their preference structure is also a remarkable result. Research limitations/implications Place-of-origin effect is not universal. Due to this fact, the results of the studies focussed on this research topic are difficult to extrapolate to other geographical areas. Practical implications The current situation in southern Europe financial sector obliges many small financial entities to undertake mergers in order to face the stability and solvency policies established by European Central Bank. In this sense, these institutions must decide whether or not to maintain their regional brand identity. The results of this study show the appropriateness of maintaining and communicating the regional origin of the entities. These findings will contribute to guiding decision making on brand management for financial entities. Originality/value To the best of the knowledge, there is a lack of research on the place-of-origin through different levels simultaneously. This paper provides a starting point for further research about this effect in the services sector.

Non-linear stability analysis of micropolar fluid lubricated journal bearings with turbulent effect

2019 ◽  
Vol 71 (1) ◽  
pp. 31-39
Author(s):  
Subrata Das ◽  
Sisir Kumar Guha
Keyword(s):  
Stability Analysis ◽  
Linear Stability ◽  
Micropolar Fluid ◽  
Journal Bearing ◽  
Journal Bearings ◽  
Turbulent Regime ◽  
Content Type ◽  
Non Linear ◽  
The Stability ◽  
Bearing System

Purpose The purpose of this paper is to investigate the effect of turbulence on the stability characteristics of finite hydrodynamic journal bearing lubricated with micropolar fluid. Design/methodology/approach The non-dimensional transient Reynolds equation has been solved to obtain the non-dimensional pressure field which in turn used to obtain the load carrying capacity of the bearing. The second-order equations of motion applicable for journal bearing system have been solved using fourth-order Runge–Kutta method to obtain the stability characteristics. Findings It has been observed that turbulence has adverse effect on stability and the whirl ratio at laminar flow condition has the lowest value. Practical implications The paper provides the stability characteristics of the finite journal bearing lubricated with micropolar fluid operating in turbulent regime which is very common in practical applications. Originality/value Non-linear stability analysis of micropolar fluid lubricated journal bearing operating in turbulent regime has not been reported in literatures so far. This paper is an effort to address the problem of non-linear stability of journal bearings under micropolar lubrication with turbulent effect. The results obtained provide useful information for designing the journal bearing system for high speed applications.

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