ROBUSTNESS, STABILITY AND EFFICIENCY OF PHAGE λ GENETIC SWITCH: DYNAMICAL STRUCTURE ANALYSIS

2004 ◽  
Vol 02 (04) ◽  
pp. 785-817 ◽  
Author(s):  
X.-M. ZHU ◽  
L. YIN ◽  
L. HOOD ◽  
P. AO

Based on the dynamical structure theory for complex networks recently developed by one of us and on the physical-chemical models for gene regulation, developed by Shea and Ackers in the 1980's, we formulate a direct and concise mathematical framework for the genetic switch controlling phage λ life cycles, which naturally includes the stochastic effect. The dynamical structure theory states that the dynamics of a complex network is determined by its four elementary components: The dissipation (analogous to degradation), the stochastic force, the driving force determined by a potential, and the transverse force. The potential may be interpreted as a landscape for the phage development in terms of attractive basins, saddle points, peaks and valleys. The dissipation gives rise to the adaptivity of the phage in the landscape defined by the potential: The phage always has the tendency to approach the bottom of the nearby attractive basin. The transverse force tends to keep the network on the equal-potential contour of the landscape. The stochastic fluctuation gives the phage the ability to search around the potential landscape by passing through saddle points.With molecular parameters in our model fixed primarily by the experimental data on wild-type phage and supplemented by data on one mutant, our calculated results on mutants agree quantitatively with the available experimental observations on other mutants for protein number, lysogenization frequency, and a lysis frequency in lysogen culture. The calculation reproduces the observed robustness of the phage λ genetic switch. This is the first mathematical description that successfully represents such a wide variety of major experimental phenomena. Specifically, we find: (1) The explanation for both the stability and the efficiency of phage λ genetic switch is the exponential dependence of saddle point crossing rate on potential barrier height, a result of the stochastic motion in a landscape; and (2) The positive feedback of cI repressor gene transcription, enhanced by the CI dimer cooperative binding, is the key to the robustness of the phage λ genetic switch against mutations and fluctuations in kinetic parameter values.

Author(s):  
Tuomo Hiippala ◽  
Malihe Alikhani ◽  
Jonas Haverinen ◽  
Timo Kalliokoski ◽  
Evanfiya Logacheva ◽  
...  

AbstractThis article introduces AI2D-RST, a multimodal corpus of 1000 English-language diagrams that represent topics in primary school natural sciences, such as food webs, life cycles, moon phases and human physiology. The corpus is based on the Allen Institute for Artificial Intelligence Diagrams (AI2D) dataset, a collection of diagrams with crowdsourced descriptions, which was originally developed to support research on automatic diagram understanding and visual question answering. Building on the segmentation of diagram layouts in AI2D, the AI2D-RST corpus presents a new multi-layer annotation schema that provides a rich description of their multimodal structure. Annotated by trained experts, the layers describe (1) the grouping of diagram elements into perceptual units, (2) the connections set up by diagrammatic elements such as arrows and lines, and (3) the discourse relations between diagram elements, which are described using Rhetorical Structure Theory (RST). Each annotation layer in AI2D-RST is represented using a graph. The corpus is freely available for research and teaching.


2020 ◽  
Vol 117 (34) ◽  
pp. 20576-20585
Author(s):  
Kim Krighaar Rasmussen ◽  
Andrés Palencia ◽  
Anders K. Varming ◽  
Habiba El-Wali ◽  
Elisabetta Boeri Erba ◽  
...  

Temperate bacteriophages can enter one of two life cycles following infection of a sensitive host: the lysogenic or the lytic life cycle. The choice between the two alternative life cycles is dependent upon a tight regulation of promoters and their cognate regulatory proteins within the phage genome. We investigated the genetic switch of TP901-1, a bacteriophage ofLactococcus lactis, controlled by the CI repressor and the modulator of repression (MOR) antirepressor and their interactions with DNA. We determined the solution structure of MOR, and we solved the crystal structure of MOR in complex with the N-terminal domain of CI, revealing the structural basis of MOR inhibition of CI binding to the DNA operator sites.15N NMR Carr–Purcell–Meiboom–Gill (CPMG) relaxation dispersion and rotating frameR1ρmeasurements demonstrate that MOR displays molecular recognition dynamics on two different time scales involving a repacking of aromatic residues at the interface with CI. Mutations in the CI:MOR binding interface impair complex formation in vitro, and when introduced in vivo, the bacteriophage switch is unable to choose the lytic life cycle showing that the CI:MOR complex is essential for proper functioning of the genetic switch. On the basis of sequence alignments, we show that the structural features of the MOR:CI complex are likely conserved among a larger family of bacteriophages from human pathogens implicated in transfer of antibiotic resistance.


2018 ◽  
Vol 41 ◽  
Author(s):  
David Danks

AbstractThe target article uses a mathematical framework derived from Bayesian decision making to demonstrate suboptimal decision making but then attributes psychological reality to the framework components. Rahnev & Denison's (R&D) positive proposal thus risks ignoring plausible psychological theories that could implement complex perceptual decision making. We must be careful not to slide from success with an analytical tool to the reality of the tool components.


2019 ◽  
Vol 12 (1) ◽  
pp. 77-87
Author(s):  
György Kovács ◽  
Rabab Benotsmane ◽  
László Dudás

Recent tendencies – such as the life-cycles of products are shorter while consumers require more complex and more unique final products – poses many challenges to the production. The industrial sector is going through a paradigm shift. The traditional centrally controlled production processes will be replaced by decentralized control, which is built on the self-regulating ability of intelligent machines, products and workpieces that communicate with each other continuously. This new paradigm known as Industry 4.0. This conception is the introduction of digital network-linked intelligent systems, in which machines and products will communicate to one another in order to establish smart factories in which self-regulating production will be established. In this article, at first the essence, main goals and basic elements of Industry 4.0 conception is described. After it the autonomous systems are introduced which are based on multi agent systems. These systems include the collaborating robots via artificial intelligence which is an essential element of Industry 4.0.


1994 ◽  
Vol 6 (3) ◽  
pp. 133-142 ◽  
Author(s):  
Steve King

Re-creating the social, economic and demographic life-cycles of ordinary people is one way in which historians might engage with the complex continuities and changes which underlay the development of early modern communities. Little, however, has been written on the ways in which historians might deploy computers, rather than card indexes, to the task of identifying such life cycles from the jumble of the sources generated by local and national administration. This article suggests that multiple-source linkage is central to historical and demographic analysis, and reviews, in broad outline, some of the procedures adopted in a study which aims at large scale life cycle reconstruction.


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