Gene expression in individual cells is highly variable and sporadic, often resulting the synthesis of mRNAs proteins bursts. Such bursting has important consequences for cell-fate decisions diverse processes ranging from HIV-1 viral infections to stem-cell differentiation. It generally assumed that bursts are geometrically distributed they arrive according a Poisson process. On other hand, recent single-cell experiments provide evidence complex burst arrival processes, highlighting need...

Summary Bacteria communicate using a process called quorum sensing which involves production, secretion and detection of signalling molecules autoinducers. Quorum allows populations bacteria to simultaneously regulate gene expression in response changes cell density. The human pathogen, Vibrio cholerae , uses quorum‐sensing circuit composed parallel systems that transduce information through four redundant regulatory small RNAs (sRNAs) (Qrr) control the numerous genes, most notably those...

Stochasticity in gene expression can give rise to fluctuations protein levels and lead phenotypic variation across a population of genetically identical cells. Recent experiments indicate that bursting feedback mechanisms play important roles controlling noise variation. A quantitative understanding the impact these factors requires analysis corresponding stochastic models. However, for models with bursting, exact analytical results distributions have not been obtained so far. Here, we...

Regulation of intrinsic noise in gene expression is essential for many cellular functions. Correspondingly, there considerable interest understanding how different molecular mechanisms impact variations protein levels across a population cells. In this work, we analyze stochastic model bursty which considers general waiting-time distributions governing arrival and decay proteins. By mapping the system to models analyzed queueing theory, derive analytical expressions steady-state...

In bacteria, the highly conserved RsmA/CsrA family of RNA-binding proteins functions as global posttranscriptional regulators acting on mRNA translation and stability. Through phenotypic complementation an rsmA mutant in Pseudomonas aeruginosa, we discovered a member, termed RsmN. Elucidation RsmN crystal structure that complex with hairpin from sRNA, RsmZ, reveals uniquely inserted α helix, which redirects polypeptide chain to form distinctly different protein fold domain-swapped dimeric...

The quorum-sensing pathway in Vibrio cholerae controls the expression of master regulator HapR, which turn regulates several important processes such as virulence factor production and biofilm formation. While HapR is known to control phenotypes, there are only a few target genes be transcriptionally regulated by HapR. In this work, we combine bioinformatic analysis with experimental validation discover set novel direct targets Our results provide evidence for two distinct binding motifs...

The intrinsic stochasticity of gene expression can lead to large variability in protein levels for genetically identical cells. Such arise from infrequent synthesis mRNAs which turn give rise bursts expression. Protein occurring has indeed been observed experimentally and recent studies have also found evidence transcriptional bursting, i.e. production bursts. Given that there are distinct experimental techniques quantifying the noise at different stages expression, it is interest derive...

CsrA/RsmA homologs are an extensive family of ribonucleic acid (RNA)-binding proteins that function as global post-transcriptional regulators controlling important cellular processes such secondary metabolism, motility, biofilm formation and the production secretion virulence factors in diverse bacterial species. While direct messenger RNA binding by has been studied detail for some genes, it is anticipated there numerous additional, yet undiscovered, targets mediate its regulation. To...

In reinforcement learning, especially in sparse-reward domains, many environment steps are required to observe reward information. order increase the frequency of such observations, "potential-based shaping" (PBRS) has been proposed as a method providing more dense signal while leaving optimal policy invariant. However, "potential function" must be carefully designed with task-dependent knowledge not deter training performance. this work, we propose "bootstrapped" shaping, termed BSRS, which...

The average-reward formulation of reinforcement learning (RL) has drawn increased interest in recent years due to its ability solve temporally-extended problems without discounting. Independently, RL algorithms have benefited from entropy-regularization: an approach used make the optimal policy stochastic, thereby more robust noise. Despite distinct benefits two approaches, combination entropy regularization with objective is not well-studied literature and there been limited development for...

In reinforcement learning, two objective functions have been developed extensively in the literature: discounted and averaged rewards. The generalization to an entropy-regularized setting has led improved robustness exploration for both of these objectives. Recently, average-reward problem was addressed using tools from large deviation theory tabular setting. This method advantage linearity, providing access optimal policy average reward-rate through properties a single matrix. this paper,...

In reinforcement learning, especially in sparse-reward domains, many environment steps are required to observe reward information. order increase the frequency of such observations, "potential-based shaping" (PBRS) has been proposed as a method providing more dense signal while leaving optimal policy invariant. However, potential function must be carefully designed with task-dependent knowledge not deter training performance. this work, we propose bootstrapped shaping, termed BS-RS, which...

Stochasticity in gene expression gives rise to fluctuations protein levels across a population of genetically identical cells. Such can lead phenotypic variation clonal populations, hence there is considerable interest quantifying noise using stochastic models. However, obtaining exact analytical results for distributions has been an intractable task all but the simplest Here, we invoke partitioning property Poisson processes develop mapping that significantly simplifies analysis models...

Using both numerical simulations and scaling arguments, we study the behavior of a random walker on one-dimensional small-world network. For properties study, find that walk obeys characteristic form. These include average number distinct sites visited by walker, mean-square displacement distribution first-return times. The form has three time regimes. At short times, does not see shortcuts effectively probes an ordinary Euclidean network in d dimensions. intermediate shows infinite Finally,...

Abstract Phenotypic heterogeneity in cancer cells is widely observed and often linked to drug resistance. In several cases, such sensitivity of tumors driven by stochastic reversible acquisition a tolerant phenotype individual even an isogenic population. Accumulating evidence further suggests that cell-fate transitions as the epithelial mesenchymal transition (EMT) are associated with this study, we analyze models phenotypic switching provide framework for analyzing EMT source variability...

The intrinsic stochasticity of gene expression can lead to large variations in protein levels across a population cells. To explain this variability, different sources messenger RNA (mRNA) fluctuations (``Poisson'' and ``telegraph'' processes) have been proposed stochastic models expression. Both Poisson telegraph scenario experimental observations noise terms ``bursts'' Correspondingly, there is considerable interest establishing relations between burst steady-state distributions for...

We describe the results of ab initio molecular-dynamics simulations liquid Ge at five temperatures ranging from 1250 to 2000 K. The electronic structure is calculated using local-density approximation and generalized norm-conserving pseudopotentials. calculations yield pair correlation function, static factor, bond-angle distribution density states, atomic self-diffusion coefficient, finally ac conductivity. Near melting, factor has experimentally observed shoulder on high-k side principal...

We study the distribution function for minimal paths in small-world networks. derive its general form, which we verify numerically, and also discuss scaling properties. Using form of this function, exact expressions average distance $\mathcal{l}\ifmmode\bar\else\textasciimacron\fi{}$ variance ${\ensuremath{\sigma}}^{2}.$ Finally, limit large system sizes obtain some approximate results.

We give exact relations for small-world networks (SWN's) which are independent of the ``degree distribution,'' i.e., distribution nearest-neighbor connections. For original SWN model, we illustrate how these can be used to obtain approximations corresponding basic probability distribution. In limit large system sizes and small disorder, use numerical studies a functional fit this Finally, scaling properties mean-square displacement random walker, determined by behavior underlying SWN.

Non-normality can cause transient growth of perturbations in thermoacoustic systems with stable eigenvalues. This low-amplitude to grow amplitudes high enough make nonlinear effects significant, and the system become nonlinearly unstable, even though it is under classical linear stability. In this paper, we have demonstrated that feature lead failure traditional controllers were designed on basis stability analysis. We also shown a simple model possible prevent ‘nonlinear driving’ by...

The term Neuro Developmental Disorder (NDD) is used for conditions caused by a dysfunction in any part of the brain or nervous system, resulting physical and/or psychological symptoms as child develops. Family children with NDD face many problems. It very important to find them and create awareness so that gaps essential services supports can be decreased.To explore parental perceptions on health & social needs NDD, understand impact disability families having disability, out availability...

The intrinsic stochasticity of gene expression can lead to large variability protein levels across a population cells. Variability (or noise) in distributions be modulated by cellular mechanisms regulation; particular, there is considerable interest understanding the role post-transcriptional regulation. To address this issue, we propose and analyze stochastic model for regulation expression. analytical solution provides insight into effects different on noise distributions. results obtained...

We present a two-dimensional, lattice based, protein-level statistical mechanical model for prion diseases (e.g., mad cow disease) with concomitant protein misfolding and aggregation. Our studies lead us to the hypothesis that observed broad incubation time distribution in epidemiological data reflect fluctuation dominated growth seeded by few nanometer scale aggregates, while much narrower distributions innoculated lab animals arise from self-averaging. ``species barriers'' infection assess...