scholarly journals Warranty analysis of a two-component system with type I stochastic dependence

Author(s):  
Nan Zhang ◽  
Mitra Fouladirad ◽  
Anne Barros

This article develops the warranty cost analysis of a two-component in-series system with stochastic dependence. From the perspectives of both the manufacturer and the consumer, the short-run total profits and costs under the non-renewing free replacement (non-renewing free replacement warranty) policy and the renewing free replacement warranty policy are derived, respectively. Numerical examples are given showing the impact of the failure dependence to both the consumer and the manufacturer.

2019 ◽  
Author(s):  
Adair L. Borges ◽  
Bardo Castro ◽  
Sutharsan Govindarajan ◽  
Tina Solvik ◽  
Veronica Escalante ◽  
...  

CRISPR-Cas systems are adaptive immune systems that protect bacteria from bacteriophage (phage) infection. To provide immunity, RNA-guided protein surveillance complexes recognize foreign nucleic acids, triggering their destruction by Cas nucleases. While the essential requirements for immune activity are well understood, the physiological cues that regulate CRISPR-Cas expression are not. Here, a forward genetic screen identifies a two-component system (KinB/AlgB), previously characterized in regulatingPseudomonas aeruginosavirulence and biofilm establishment, as a regulator of the biogenesis and activity of the Type I-F CRISPR-Cas system. Downstream of the KinB/AlgB system, activators of biofilm production AlgU (a σEorthologue) and AlgR, act as repressors of CRISPR-Cas activity during planktonic and surface-associated growth. AmrZ, another biofilm activator, functions as a surface-specific repressor of CRISPR-Cas immunity.Pseudomonasphages and plasmids have taken advantage of this regulatory scheme, and carry hijacked homologs of AmrZ, which are functional CRISPR-Cas repressors. This suggests that while CRISPR-Cas regulation may be important to limit self-toxicity, endogenous repressive pathways represent a vulnerability for parasite manipulation.


mBio ◽  
2017 ◽  
Vol 8 (3) ◽  
Author(s):  
Rong Gao ◽  
Ann M. Stock

ABSTRACT Cells rely on accurate control of signaling systems to adapt to environmental perturbations. System deactivation upon stimulus removal is as important as activation of signaling pathways. The two-component system (TCS) is one of the major bacterial signaling schemes. In many TCSs, phosphatase activity of the histidine kinase (HK) is believed to play an essential role in shutting off the pathway and resetting the system to the prestimulus state. Two basic challenges are to understand the dynamic behavior of system deactivation and to quantitatively evaluate the role of phosphatase activity under natural cellular conditions. Here we report a kinetic analysis of the response to shutting off the archetype Escherichia coli PhoR-PhoB TCS pathway using both transcription reporter assays and in vivo phosphorylation analyses. Upon removal of the stimulus, the pathway is shut off by rapid dephosphorylation of the PhoB response regulator (RR) while PhoB-regulated gene products gradually reset to prestimulus levels through growth dilution. We developed an approach combining experimentation and modeling to assess in vivo kinetic parameters of the phosphatase activity with kinetic data from multiple phosphatase-diminished mutants. This enabled an estimation of the PhoR phosphatase activity in vivo , which is much stronger than the phosphatase activity of PhoR cytoplasmic domains analyzed in vitro . We quantitatively modeled how strong the phosphatase activity needs to be to suppress nonspecific phosphorylation in TCSs and discovered that strong phosphatase activity of PhoR is required for cross-phosphorylation suppression. IMPORTANCE Activation of TCSs has been extensively studied; however, the kinetics of shutting off TCS pathways is not well characterized. We present comprehensive analyses of the shutoff response for the PhoR-PhoB system that reveal the impact of phosphatase activity on shutoff kinetics. This allows development of a quantitative framework not only to characterize the phosphatase activity in the natural cellular environment but also to understand the requirement for specific strengths of phosphatase activity to suppress nonspecific phosphorylation. Our model suggests that the ratio of the phosphatase rate to the nonspecific phosphorylation rate correlates with TCS expression levels and the ratio of the RR to HK, which may contribute to the great diversity of enzyme levels and activities observed in different TCSs.


2012 ◽  
Vol 80 (10) ◽  
pp. 3438-3453 ◽  
Author(s):  
Aurélia Delauné ◽  
Sarah Dubrac ◽  
Charlène Blanchet ◽  
Olivier Poupel ◽  
Ulrike Mäder ◽  
...  

ABSTRACTThe WalKR two-component system is essential for the viability ofStaphylococcus aureus, playing a central role in controlling cell wall metabolism. We produced a constitutively active form of WalR inS. aureusthrough a phosphomimetic amino acid replacement (WalRc, D55E). The strain displayed significantly increased biofilm formation and alpha-hemolytic activity. Transcriptome analysis was used to determine the full extent of the WalKR regulon, revealing positive regulation of major virulence genes involved in host matrix interactions (efb,emp,fnbA, andfnbB), cytolysis (hlgACB,hla, andhlb), and innate immune defense evasion (scn,chp, andsbi), through activation of the SaeSR two-component system. The impact on pathogenesis of varying cell envelope dynamics was studied using a murine infection model, showing that strains producing constitutively active WalRcare strongly diminished in their virulence due to early triggering of the host inflammatory response associated with higher levels of released peptidoglycan fragments. Indeed, neutrophil recruitment and proinflammatory cytokine production were significantly increased when the constitutively activewalRcallele was expressed, leading to enhanced bacterial clearance. Taken together, our results indicate that WalKR play an important role in virulence and eliciting the host inflammatory response by controlling autolytic activity.


2016 ◽  
Vol 23 (1) ◽  
pp. 168-186 ◽  
Author(s):  
Muhammad Shahbaz ◽  
Ronald Ravinesh Kumar ◽  
Stanislav Ivanov ◽  
Nanthakumar Loganathan

This article revisits the tourism-growth nexus in Malaysia using time series quarterly data over the period 1975–2013. The authors examine the impact of tourism using two separate indicators – tourism receipts per capita and visitor arrivals per capita. Using the augmented Solow production function and the autoregressive distributed lag bounds procedure, they also incorporate trade openness and financial development and account for structural breaks in series. The results show the evidence of cointegration between the variables. Assessing the long-run results using both indicators of tourism demand, it is noted that the elasticity coefficient of tourism is 0.13 and 0.10 when considering visitor arrivals and tourism receipts (in per capita terms), respectively. Notably, the impact of tourism demand is marginally higher with visitor arrivals. The elasticity of trade openness is 0.19, that of financial development is 0.09 and that of capital share is 0.15. In the short run, the coefficient of tourism is marginally negative, and for financial development and trade openness, it is 0.01 and 0.18, respectively. The Granger causality tests show bidirectional causation between tourism and output per capita, financial development and tourism and trade openness and tourism demand, duly indicating the feedback or mutually reinforcing impact between the variables and providing evidence that tourism is central to enhancing the key sectors and the overall income level.


2005 ◽  
Vol 22 (01) ◽  
pp. 105-119 ◽  
Author(s):  
V. S. S. YADAVALLI ◽  
A. BEKKER ◽  
J. PAUW

The steady-state availability of a two-component system in series and parallel subject to individual failures (I-failures) and common-cause shock (CCS) failures is studied from a Bayesian viewpoint with different types of priors assumed for the unknown parameters in the system. Monte Carlo simulation is used to derive the posterior distribution for the steady-state availability and subsequently the highest posterior density intervals. A numerical example illustrates the results.


2003 ◽  
Vol 13 (05) ◽  
pp. 1303-1308 ◽  
Author(s):  
SÁNDOR KOVÁCS

In this paper we consider a model for the behavior of students in graduate programs at neighboring universities which is a modified form of the model proposed by [Scheurle & Seydel, 2000], and observe that the stationary solution of this two-component system becomes unstable in the presence of diffusion. We assume that both types of individuals are continuously distributed throughout a bounded two-dimensional spatial domain of two types (regular hexagon and rhombus), across whose boundaries there is no migration, and which simultaneously undergo simple (Fickian) diffusion but the spatial flow is influenced not only by its own but also by the other's density (cross diffusion). We will show that at a critical value of a parameter a Turing bifurcation takes place: a spatially nonhomogenous solution (pattern) arises.


2006 ◽  
Vol 188 (23) ◽  
pp. 8109-8117 ◽  
Author(s):  
Paula Ann Kivistik ◽  
Marta Putrinš ◽  
Külliki Püvi ◽  
Heili Ilves ◽  
Maia Kivisaar ◽  
...  

ABSTRACT As reported, the two-component system ColRS is involved in two completely different processes. It facilitates the root colonization ability of Pseudomonas fluorescens and is necessary for the Tn4652 transposition-dependent accumulation of phenol-utilizing mutants in Pseudomonas putida. To determine the role of the ColRS system in P. putida, we searched for target genes of response regulator ColR by use of a promoter library. Promoter screening was performed on phenol plates to mimic the conditions under which the effect of ColR on transposition was detected. The library screen revealed the porin-encoding gene oprQ and the alginate biosynthesis gene algD occurring under negative control of ColR. Binding of ColR to the promoter regions of oprQ and algD in vitro confirmed its direct involvement in regulation of these genes. Additionally, the porin-encoding gene ompA PP0773 and the type I pilus gene csuB were also identified in the promoter screen. However, it turned out that ompA PP0773 and csuB were actually affected by phenol and that the influence of ColR on these promoters was indirect. Namely, our results show that ColR is involved in phenol tolerance of P. putida. Phenol MIC measurement demonstrated that a colR mutant strain did not tolerate elevated phenol concentrations. Our data suggest that increased phenol susceptibility is also the reason for inhibition of transposition of Tn4652 in phenol-starving colR mutant bacteria. Thus, the current study revealed the role of the ColRS two-component system in regulation of membrane functionality, particularly in phenol tolerance of P. putida.


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