scholarly journals Stability analysis of a signaling circuit with dual species of GTPase switches

2020 ◽  
Author(s):  
Lucas Martins Stolerman ◽  
Pradipta Ghosh ◽  
Padmini Rangamani
Keyword(s):  
Stability Analysis ◽  
Feedback Loop ◽  
Network Motif ◽  
Bound State ◽  
Steady States ◽  
Eukaryotic Cells ◽  
Nucleotide Exchange ◽  
Organelle Biogenesis ◽  
Stable States ◽  
Wide Range

GTPases are molecular switches that regulate a wide range of cellular processes, such as organelle biogenesis, position, shape, and function, vesicular transport between organelles, and signal transduction. These hydrolase enzymes operate by toggling between an active "ON") guanosine triphosphate (GTP)-bound state and an inactive ("OFF") guanosine diphosphate (GDP)-bound state; such a toggle is regulated by GEFs (guanine nucleotide exchange factors) and GAPs (GTPase activating proteins). Here we propose a model for a network motif between monomeric (m) and trimeric (t) GTPases assembled exclusively in eukaryotic cells of multicellular organisms. We develop a system of ordinary differential equations in which these two classes of GTPases are interlinked conditional to their ON/OFF states within a motif through coupling and feedback loops. We provide explicit formulae for the steady states of the system and perform classical local stability analysis to systematically investigate the role of the different connections between the GTPase switches. Interestingly, a coupling of the active mGTPase to the GEF of the tGTPase was sufficient to provide two locally stable states: one where both active/inactive forms of the mGTPase can be interpreted as having low concentrations and the other where both m- and tGTPase have high concentrations. Moreover, when a feedback loop from the GEF of the tGTPase to the GAP of the mGTPase was added to the coupled system, two other locally stable states emerged, both having the tGTPase inactivated and being interpreted as having low active tGTPase concentrations. Finally, the addition of a second feedback loop, from the active tGTPase to the GAP of the mGTPase, gives rise to a family of steady states that can be parametrized by a range of inactive tGTPase concentrations. Our findings reveal that the coupling of these two different GTPase motifs can dramatically change their steady state behaviors and shed light on how such coupling may impact signaling mechanisms in eukaryotic cells.

The effect of wavy surface on boundary layer instabilities of an airfoil

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Zbigniew Rarata
Keyword(s):  
Stability Analysis ◽  
Feedback Loop ◽  
Flow Fields ◽  
Wavy Surface ◽  
Content Type ◽  
Spatial Stability ◽  
Stability Analyses ◽  
Acoustic Feedback ◽  
Wide Range ◽  
Naca 0012

Purpose The purpose of this paper is to investigate airfoil’s tonal noise reduction mechanism when deploying surface irregularities, such as surface waviness by means of spatial stability analyses. Design/methodology/approach Flow field calculations over smooth and wavy-surface NACA 0012 airfoils at 2° angle of attack and at Reynolds number of 200,000 are performed using the large eddy simulation (LES) approach. Three geometrical configurations are considered: a smooth NACA 0012 airfoil, wavy surface on the suction side (SS) and wavy surface on the pressure side (PS). The spatial stability analyses using the LES-generated flow fields are conducted and validated against the Orr-Sommerfeld stability analysis for the smooth airfoil configuration. Findings The spatial stability analyses show that inclusion of the wavy-type modification on the SS of the airfoil does not lead to altering of the acoustic feedback loop mechanism, with respect to the mechanism observed for the smooth airfoil configuration. In contrast, applying the surface modifications to the airfoil PS leads to a significant reduction of the amplification range of disturbances in the vicinity of the trailing edge for the frequency of the acoustic feedback loop mechanism. Practical implications The spatial analyses using, for example, LES-generated flow fields can be widely used to determine acoustic sources and associated distributions of amplifications for a wide range of applications in the aeroacoustics. Originality/value The spatial stability analysis approach based on flow fields computed a priori using the LES method has been introduced, validated and used to determine behaviour of the acoustic feedback loop when accurate reconstruction of geometry effects is required.

Asymptotic and stability analysis of solutions for a Keller Segel chemotaxis model

2021 ◽  
pp. 1063293X2199808
Author(s):  
Kai Qu ◽  
Chanjie Li ◽  
Feiyu Zhang
Keyword(s):  
Asymptotic Behavior ◽  
Stability Analysis ◽  
Blow Up ◽  
Upper And Lower Solutions ◽  
Neumann Boundary ◽  
Model Solution ◽  
Steady States ◽  
Chemotaxis Model ◽  
Local Asymptotic Stability ◽  
Wide Range

A kind of Keller Segel chemotaxis model has a wide range of applications, but its coupling relationship is very complex. The commonly used method of constructing the upper and lower solutions is no longer suitable for the model solution, which results in a long time for its analysis. In this paper, we propose a method to analyze the asymptotic behavior and stability of a Keller Segel chemotaxis model. The previous methods of first formally and then rigorously, the asymptotic expansion of these monotone steady states, and then we use this fine information on the spike to prove its local asymptotic stability. Moreover, we obtain the uniqueness of such steady states. The asymptotic behavior of the solution of a Keller Segel chemotaxis model is analyzed, and the asymptotic rate is calculated; According to the limitation of Neumann boundary condition, the complete blow up of chemotaxis model solution and the stability of the initial value of the complete blow up time are studied, and the asymptotic and stability analysis of a kind of Keller Segel chemotaxis model solution is completed. The experimental results show that the proposed method takes less time to solve a kind of Keller Segel chemotaxis model, improves the efficiency of the solution, and the accuracy of the solution is higher.

scholarly journals Matrix Product State Simulations of Non-Equilibrium Steady States and Transient Heat Flows in the Two-Bath Spin-Boson Model at Finite Temperatures

Entropy ◽  
2021 ◽  
Vol 23 (1) ◽  
pp. 77
Author(s):  
Angus J. Dunnett ◽  
Alex W. Chin
Keyword(s):  
Finite Temperature ◽  
Open Quantum Systems ◽  
Quantum Systems ◽  
Steady States ◽  
Matrix Product ◽  
Open Quantum ◽  
Matrix Product State ◽  
Wide Range ◽  
Boson Model ◽  
Non Equilibrium

Simulating the non-perturbative and non-Markovian dynamics of open quantum systems is a very challenging many body problem, due to the need to evolve both the system and its environments on an equal footing. Tensor network and matrix product states (MPS) have emerged as powerful tools for open system models, but the numerical resources required to treat finite-temperature environments grow extremely rapidly and limit their applications. In this study we use time-dependent variational evolution of MPS to explore the striking theory of Tamascelli et al. (Phys. Rev. Lett. 2019, 123, 090402.) that shows how finite-temperature open dynamics can be obtained from zero temperature, i.e., pure wave function, simulations. Using this approach, we produce a benchmark dataset for the dynamics of the Ohmic spin-boson model across a wide range of coupling strengths and temperatures, and also present a detailed analysis of the numerical costs of simulating non-equilibrium steady states, such as those emerging from the non-perturbative coupling of a qubit to baths at different temperatures. Despite ever-growing resource requirements, we find that converged non-perturbative results can be obtained, and we discuss a number of recent ideas and numerical techniques that should allow wide application of MPS to complex open quantum systems.

New insight into the molecular switch mechanism of human Rho family proteins: shifting a paradigm

2013 ◽  
Vol 394 (1) ◽  
pp. 89-95 ◽  
Author(s):  
Mamta Jaiswal ◽  
Eyad Kalawy Fansa ◽  
Radovan Dvorsky ◽  
Mohammad Reza Ahmadian
Keyword(s):  
Quantitative Analysis ◽  
Bound State ◽  
Molecular Switch ◽  
Nucleotide Exchange ◽  
Gtp Binding ◽  
Switch Mechanism ◽  
Rho Family ◽  
Rho Family Proteins ◽  
Insight Into ◽  
Made In

Abstract Major advances have been made in understanding the structure, function and regulation of the small GTP-binding proteins of the Rho family and their involvement in multiple cellular process and disorders. However, intrinsic nucleotide exchange and hydrolysis reactions, which are known to be fundamental to Rho family proteins, have been partially investigated in the case of RhoA, Rac1 and Cdc42, but for others not at all. Here we present a comprehensive and quantitative analysis of the molecular switch functions of 15 members of the Rho family that enabled us to propose an active GTP-bound state for the rather uncharacterized isoforms RhoD and Rif under equilibrium and quiescent conditions.

scholarly journals Hijacking Components of the Cellular Secretory Pathway for Replication of Poliovirus RNA

2006 ◽  
Vol 81 (2) ◽  
pp. 558-567 ◽  
Author(s):  
George A. Belov ◽  
Nihal Altan-Bonnet ◽  
Gennadiy Kovtunovych ◽  
Catherine L. Jackson ◽  
Jennifer Lippincott-Schwartz ◽  
...  
Keyword(s):  
Secretory Pathway ◽  
Brefeldin A ◽  
Rna Replication ◽  
Bound State ◽  
Small Gtpases ◽  
Nucleotide Exchange ◽  
Virus Growth ◽  
Guanine Nucleotide Exchange ◽  
Membrane Reorganization

ABSTRACT Infection of cells with poliovirus induces a massive intracellular membrane reorganization to form vesicle-like structures where viral RNA replication occurs. The mechanism of membrane remodeling remains unknown, although some observations have implicated components of the cellular secretory and/or autophagy pathways. Recently, we showed that some members of the Arf family of small GTPases, which control secretory trafficking, became membrane-bound after the synthesis of poliovirus proteins in vitro and associated with newly formed membranous RNA replication complexes in infected cells. The recruitment of Arfs to specific target membranes is mediated by a group of guanine nucleotide exchange factors (GEFs) that recycle Arf from its inactive, GDP-bound state to an active GTP-bound form. Here we show that two different viral proteins independently recruit different Arf GEFs (GBF1 and BIG1/2) to the new structures that support virus replication. Intracellular Arf-GTP levels increase ∼4-fold during poliovirus infection. The requirement for these GEFs explains the sensitivity of virus growth to brefeldin A, which can be rescued by the overexpression of GBF1. The recruitment of Arf to membranes via specific GEFs by poliovirus proteins provides an important clue toward identifying cellular pathways utilized by the virus to form its membranous replication complex.

scholarly journals The nucleoporin RanBP2 tethers the cAMP effector Epac1 and inhibits its catalytic activity

2011 ◽  
Vol 193 (6) ◽  
pp. 1009-1020 ◽  
Author(s):  
Martijn Gloerich ◽  
Marjolein J. Vliem ◽  
Esther Prummel ◽  
Lars A.T. Meijer ◽  
Marije G.A. Rensen ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Negative Regulator ◽  
Camp Signaling ◽  
Nuclear Pore ◽  
Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Wide Range

Cyclic adenosine monophosphate (cAMP) is a second messenger that relays a wide range of hormone responses. In this paper, we demonstrate that the nuclear pore component RanBP2 acts as a negative regulator of cAMP signaling through Epac1, a cAMP-regulated guanine nucleotide exchange factor for Rap. We show that Epac1 directly interacts with the zinc fingers (ZNFs) of RanBP2, tethering Epac1 to the nuclear pore complex (NPC). RanBP2 inhibits the catalytic activity of Epac1 in vitro by binding to its catalytic CDC25 homology domain. Accordingly, cellular depletion of RanBP2 releases Epac1 from the NPC and enhances cAMP-induced Rap activation and cell adhesion. Epac1 also is released upon phosphorylation of the ZNFs of RanBP2, demonstrating that the interaction can be regulated by posttranslational modification. These results reveal a novel mechanism of Epac1 regulation and elucidate an unexpected link between the NPC and cAMP signaling.

Mechanisms of Giardia lamblia differentiation into cysts

1997 ◽  
Vol 61 (3) ◽  
pp. 294-304
Author(s):  
H D Luján ◽  
M R Mowatt ◽  
T E Nash
Keyword(s):  
Giardia Lamblia ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Life Cycles ◽  
Eukaryotic Cells ◽  
Organelle Biogenesis ◽  
Adaptive Responses ◽  
Specific Stimulus ◽  
Adverse Conditions

Microbiologists have long been intrigued by the ability of parasitic organisms to adapt to changes in the environment. Since most parasites occupy several niches during their journey between vectors and hosts, they have developed adaptive responses which allow them to survive under adverse conditions. Therefore, the life cycles of protozoan and helminthic parasites are excellent models with which to study numerous mechanisms involved in cell differentiation, such as the regulation of gene expression, signal transduction pathways, and organelle biogenesis. Unfortunately, many of these studies are very difficult because the conditions needed to elicit developmental changes in parasites remain undetermined in most cases. Recently, several interesting findings were reported on the process of differentiation of Giardia lamblia trophozoites into cysts. G. lamblia is a flagellated protozoan that inhabits the upper small intestine of its vertebrate host and is a major cause of enteric disease worldwide. It belongs to the earliest identified lineage among eukaryotes and therefore offers a unique insight into the progression from primitive to more complex eukaryotic cells. The discovery of a specific stimulus that induces trophozoites to differentiate into cysts, the identification and characterization of encystation-specific molecules, the elucidation of novel biochemical pathways, and the development of useful reagents and techniques have made this parasite an excellent model with which to study differentiation in eukaryotic cells. In this review, we summarize the most recent fundings on several aspects of Giardia differentiation and discuss the significance of these findings within the context of current knowledge in the field.

Thermoacoustic Stability Analysis of a Full-Annular Lean Combustor for Heavy-Duty Applications

2021 ◽  
Author(s):  
Daniele Pampaloni ◽  
Antonio Andreini ◽  
Alessandro Marini ◽  
Giovanni Riccio ◽  
Gianni Ceccherini
Keyword(s):  
Stability Analysis ◽  
Gas Turbine ◽  
Flame Temperature ◽  
Numerical Procedure ◽  
Pollutant Emissions ◽  
Computational Time ◽  
Heavy Duty ◽  
Operational Parameters ◽  
3D Fem ◽  
Wide Range

Abstract Thermoacoustic characterization of gas turbine combustion systems is of primary importance for successful development of gas turbine technology, to meet the stringent targets on pollutant emissions. In this context, it becomes more and more necessary to develop reliable tools to be used in the industrial design process. The dynamics of a lean-premixed full-annular combustor for heavy-duty applications has been numerically studied in this work. The well-established CFD-SI method has been used to investigate the flame response varying operational parameters such as the flame temperature (global equivalence ratio) and the fuel split between premixed and pilot fuel injections: such a wide range experimental characterization represents an opportunity to validate the employed numerical methods and to give a deeper insight into the flame dynamics. URANS simulations have been performed, due to their affordable computational costs from the industrial perspective, after validating their accuracy through the comparison against LES results. Furthermore, an approach where the pilot and the premixed flame responses are analyzed separately is proposed, exploiting the independence of their evolution. The calculated FTFs have been implemented in a 3D FEM model of the chamber, in order to perform linear stability analysis and to validate the numerical approach. A boundary condition for rotational periodicity based on Bloch-Wave theory has been implemented into the Helmholtz solver and validated against full-annular chamber simulations, allowing a significant reduction in computational time. The reliability of the numerical procedure has been assessed through the comparison against full-annular experimental results.

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