Stochastic resonances in a distributed genetic broadcasting system: the NF?B/I?B paradigm.
ABSTRACT: Gene regulatory networks must relay information from extracellular signals to downstream genes in an efficient, timely and coherent manner. Many complex functional tasks such as the immune response require system-wide broadcasting of information not to one but to many genes carrying out distinct functions whose dynamical binding and unbinding characteristics are widely distributed. In such broadcasting networks, the intended target sites are also often dwarfed in number by the even more numerous non-functional binding sites. Taking the genetic regulatory network of NF?B as an exemplary system we explore the impact of having numerous distributed sites on the stochastic dynamics of oscillatory broadcasting genetic networks pointing out how resonances in binding cycles control the network's specificity and performance. We also show that active kinetic regulation of binding and unbinding through molecular stripping of DNA bound transcription factors can lead to a higher coherence of gene-co-expression and synchronous clearance.
Project description:As the digitization is integrated into daily life, media including video and audio are heavily transferred over the Internet nowadays. Voice-over-Internet Protocol (VoIP), the most popular and mature technology, becomes the focus attracting many researches and investments. However, most of the existing studies focused on a one-to-one communication model in a homogeneous network, instead of one-to-many broadcasting model among diverse embedded devices in a heterogeneous network. In this paper, we present the implementation of a VoIP broadcasting service on the open source-Linphone-in a heterogeneous network environment, including WiFi, 3G, and LAN networks. The proposed system featuring VoIP broadcasting over heterogeneous networks can be integrated with heterogeneous agile devices, such as embedded devices or mobile phones. VoIP broadcasting over heterogeneous networks can be integrated into modern smartphones or other embedded devices; thus when users run in a traditional AM/FM signal unreachable area, they still can receive the broadcast voice through the IP network. Also, comprehensive evaluations are conducted to verify the effectiveness of the proposed implementation.
Project description:BACKGROUND:Information and emotions towards public health issues could spread widely through online social networks. Although aggregate metrics on the volume of information diffusion are available, we know little about how information spreads on online social networks. Health information could be transmitted from one to many (i.e. broadcasting) or from a chain of individual to individual (i.e. viral spreading). The aim of this study is to examine the spreading pattern of Ebola information on Twitter and identify influential users regarding Ebola messages. METHODS:Our data was purchased from GNIP. We obtained all Ebola-related tweets posted globally from March 23, 2014 to May 31, 2015. We reconstructed Ebola-related retweeting paths based on Twitter content and the follower-followee relationships. Social network analysis was performed to investigate retweeting patterns. In addition to describing the diffusion structures, we classify users in the network into four categories (i.e., influential user, hidden influential user, disseminator, common user) based on following and retweeting patterns. RESULTS:On average, 91% of the retweets were directly retweeted from the initial message. Moreover, 47.5% of the retweeting paths of the original tweets had a depth of 1 (i.e., from the seed user to its immediate followers). These observations suggested that the broadcasting was more pervasive than viral spreading. We found that influential users and hidden influential users triggered more retweets than disseminators and common users. Disseminators and common users relied more on the viral model for spreading information beyond their immediate followers via influential and hidden influential users. CONCLUSIONS:Broadcasting was the dominant mechanism of information diffusion of a major health event on Twitter. It suggests that public health communicators can work beneficially with influential and hidden influential users to get the message across, because influential and hidden influential users can reach more people that are not following the public health Twitter accounts. Although both influential users and hidden influential users can trigger many retweets, recognizing and using the hidden influential users as the source of information could potentially be a cost-effective communication strategy for public health promotion. However, challenges remain due to uncertain credibility of these hidden influential users.
Project description:Odor representations are initially formed in the olfactory bulb, which contains a topographic glomerular map of odor molecular features. The bulb transmits sensory information directly to piriform cortex, where it is encoded by distributed ensembles of pyramidal cells without spatial order. Intriguingly, piriform cortex pyramidal cells project back to the bulb, but the information contained in this feedback projection is unknown. Here, we use imaging in awake mice to directly monitor activity in the presynaptic boutons of cortical feedback fibers. We show that the cortex provides the bulb with a rich array of information for any individual odor and that cortical feedback is dependent on brain state. In contrast to the stereotyped, spatial arrangement of olfactory bulb glomeruli, cortical inputs tuned to different odors commingle and indiscriminately target individual glomerular channels. Thus, the cortex modulates early odor representations by broadcasting sensory information diffusely onto spatially ordered bulbar circuits.
Project description:This paper proposes a tree-based adaptive broadcasting (TAB) algorithm for data dissemination to improve data access efficiency. The proposed TAB algorithm first constructs a broadcast tree to determine the broadcast frequency of each data and splits the broadcast tree into some broadcast wood to generate the broadcast program. In addition, this paper develops an analytical model to derive the mean access latency of the generated broadcast program. In light of the derived results, both the index channel's bandwidth and the data channel's bandwidth can be optimally allocated to maximize bandwidth utilization. This paper presents experiments to help evaluate the effectiveness of the proposed strategy. From the experimental results, it can be seen that the proposed mechanism is feasible in practice.
Project description:Recent research suggests that more and more citizens select news and information that is congruent with their existing political preferences. This increase in political selective exposure (PSE) has allegedly led to an increase in polarization. The vast majority of studies stem from the US case with a particular media and political system. We contend that there are good reasons to believe PSE is less prevalent in other systems. We test this using latent profile analysis with national survey data from the Netherlands (n = 2,833). We identify four types of media use profiles and indeed only find partial evidence of PSE. In particular, we find that public broadcasting news cross-cuts all cleavages. This research note offers an important antidote in what is considered a universal phenomenon. We do find, however, a relatively large segment of citizens opting out of news consumption despite the readily available news in today's media landscape.
Project description:BACKGROUND:Literature provides mixed results regarding the influence of large-scale sporting events on emergency department attendance. To contribute to the research on the subject, we sought to evaluate whether the broadcasting of major tennis tournaments, one of the most popular sports in Switzerland, has an impact on patient admission rates in emergency units in Geneva including 1) type of match 2) the role of a Swiss player, 3) degree of triage, 4) reason of attendance and 5) age of patients. METHODS:Admission rates between periods with tennis matches regarding the semi-finals and finals of 3 major tennis tournaments were compared to equivalent periods without matches from May 2013 to August 2017. Patient admission data was retrieved retrospectively from administrative databases of two Outpatient Emergency Units in Geneva. Patients' admission rates in periods with and without a tennis match were investigated using a negative binomial regression model with mixed effects. RESULTS:We observed a statistically significant decrease (-?10%, 95% CI -17 to -?2, p?=?0.015) in admission rates in periods with a tennis match compared to periods without a tennis match, more pronounced during finals (-?15%, 95% CI -26 to -?3, p?=?0.017) than during semi-finals (-?7%, -?16 to 2, p?=?0.13). In addition, this effect was more pronounced in patients aged between 26 to 64?years of age, a category representing professionnally active people. No modification in the admission rates was detected in the hours preceding and following the matches, nor in type of consultations (traumatology vs non traumatology related admissions). CONCLUSION:Although modest, the results support the hypothesis that the broadcasting of large-scale sporting events such as tennis matches decreases admission rates in emergency units. Further research is required to explore for a potential causal relationship.
Project description:Gene regulatory networks are multistable dynamical systems in which attractor states represent cell phenotypes. Spontaneous, noise-induced transitions between these states are thought to underlie critical cellular processes, including cell developmental fate decisions, phenotypic plasticity in fluctuating environments, and carcinogenesis. As such, there is increasing interest in the development of theoretical and computational approaches that can shed light on the dynamics of these stochastic state transitions in multistable gene networks. We applied a numerical rare-event sampling algorithm to study transition paths of spontaneous noise-induced switching for a ubiquitous gene regulatory network motif, the bistable toggle switch, in which two mutually repressive genes compete for dominant expression. We find that the method can efficiently uncover detailed switching mechanisms that involve fluctuations both in occupancies of DNA regulatory sites and copy numbers of protein products. In addition, we show that the rate parameters governing binding and unbinding of regulatory proteins to DNA strongly influence the switching mechanism. In a regime of slow DNA-binding/unbinding kinetics, spontaneous switching occurs relatively frequently and is driven primarily by fluctuations in DNA-site occupancies. In contrast, in a regime of fast DNA-binding/unbinding kinetics, switching occurs rarely and is driven by fluctuations in levels of expressed protein. Our results demonstrate how spontaneous cell phenotype transitions involve collective behavior of both regulatory proteins and DNA. Computational approaches capable of simulating dynamics over many system variables are thus well suited to exploring dynamic mechanisms in gene networks.
Project description:Vehicular ad hoc networks (VANETs) are one special type of ad hoc networks that involves vehicles on roads. Typically like ad hoc networks, broadcast approach is used for data dissemination. Blind broadcast to each and every node results in exchange of useless and irrelevant messages and hence creates an overhead. Unicasting is not preferred in ad-hoc networks due to the dynamic topology and the resource requirements as compared to broadcasting. Simple broadcasting techniques create several problems on privacy, disturbance, and resource utilization. In this paper, we propose media mixing algorithm to decide what information should be provided to each user and how to provide such information. Results obtained through simulation show that fewer number of keys are needed to share compared to simple broadcasting. Privacy is also enhanced through this approach.
Project description:Eukaryotic transcription factors in the NF-?B family are central components of an extensive genetic network that activates cellular responses to inflammation and to a host of other external stressors. This network consists of feedback loops that involve the inhibitor I?B?, numerous downstream functional targets, and still more numerous binding sites that do not appear to be directly functional. Under steady stimulation, the regulatory network of NF-?B becomes oscillatory, and temporal patterns of NF-?B pulses appear to govern the patterns of downstream gene expression needed for immune response. Understanding how the information from external stress passes to oscillatory signals and is then ultimately relayed to gene expression is a general issue in systems biology. Recently, in vitro kinetic experiments as well as molecular simulations suggest that active stripping of NF-?B by I?B? from its binding sites can modify the traditional systems biology view of NF-?B/I?B? gene circuits. In this work, we revise the commonly adopted minimal model of the NF-?B regulatory network to account for the presence of the large number of binding sites for NF-?B along with dissociation from these sites that may proceed either by passive unbinding or by active molecular stripping. We identify regimes where the kinetics of target and decoy unbinding and molecular stripping enter a dynamic tug of war that may either compensate each other or amplify nuclear NF-?B activity, leading to distinct oscillatory patterns. Our finding that decoys and stripping play a key role in shaping the NF-?B oscillations suggests strategies to control NF-?B responses by introducing artificial decoys therapeutically.
Project description:Binding and unbinding of transcription regulators at operator sites constitute a primary mechanism for gene regulation. While many cellular factors are known to regulate their binding, little is known on how cells can modulate their unbinding for regulation. Using nanometer-precision single-molecule tracking, we study the unbinding kinetics from DNA of two metal-sensing transcription regulators in living Escherichia coli cells. We find that they show unusual concentration-dependent unbinding kinetics from chromosomal recognition sites in both their apo and holo forms. Unexpectedly, their unbinding kinetics further varies with the extent of chromosome condensation, and more surprisingly, varies in opposite ways for their apo-repressor versus holo-activator forms. These findings suggest likely broadly relevant mechanisms for facile switching between transcription activation and deactivation in vivo and in coordinating transcription regulation of resistance genes with the cell cycle.