Basic Functional Modules Research Articles

In Silico Knockout Studies of Xenophagic Capturing of Salmonella.

The degradation of cytosol-invading pathogens by autophagy, a process known as xenophagy, is an important mechanism of the innate immune system. Inside the host, Salmonella Typhimurium invades epithelial cells and resides within a specialized intracellular compartment, the Salmonella-containing vacuole. A fraction of these bacteria does not persist inside the vacuole and enters the host cytosol. Salmonella Typhimurium that invades the host cytosol becomes a target of the autophagy machinery for degradation. The xenophagy pathway has recently been discovered, and the exact molecular processes are not entirely characterized. Complete kinetic data for each molecular process is not available, so far. We developed a mathematical model of the xenophagy pathway to investigate this key defense mechanism. In this paper, we present a Petri net model of Salmonella xenophagy in epithelial cells. The model is based on functional information derived from literature data. It comprises the molecular mechanism of galectin-8-dependent and ubiquitin-dependent autophagy, including regulatory processes, like nutrient-dependent regulation of autophagy and TBK1-dependent activation of the autophagy receptor, OPTN. To model the activation of TBK1, we proposed a new mechanism of TBK1 activation, suggesting a spatial and temporal regulation of this process. Using standard Petri net analysis techniques, we found basic functional modules, which describe different pathways of the autophagic capture of Salmonella and reflect the basic dynamics of the system. To verify the model, we performed in silico knockout experiments. We introduced a new concept of knockout analysis to systematically compute and visualize the results, using an in silico knockout matrix. The results of the in silico knockout analyses were consistent with published experimental results and provide a basis for future investigations of the Salmonella xenophagy pathway.

Spatiotemporal variation of mammalian protein complex stoichiometries.

BackgroundRecent large-scale studies revealed cell-type specific proteomes. However, protein complexes, the basic functional modules of a cell, have been so far mostly considered as static entities with well-defined structures. The co-expression of their members has not been systematically charted at the protein level.ResultsWe used measurements of protein abundance across 11 cell types and five temporal states to analyze the co-expression and the compositional variations of 182 well-characterized protein complexes. We show that although the abundance of protein complex members is generally co-regulated, a considerable fraction of all investigated protein complexes is subject to stoichiometric changes. Compositional variation is most frequently seen in complexes involved in chromatin regulation and cellular transport, and often involves paralog switching as a mechanism for the regulation of complex stoichiometry. We demonstrate that compositional signatures of variable protein complexes have discriminative power beyond individual cell states and can distinguish cancer cells from healthy ones.ConclusionsOur work demonstrates that many protein complexes contain variable members that cause distinct stoichometries and functionally fine-tune complexes spatiotemporally. Only a fraction of these compositional variations is mediated by changes in transcription and other mechanisms regulating protein abundance contribute to determine protein complex stoichiometries. Our work highlights the superior power of proteome profiles to study protein complexes and their variants across cell states.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-0912-5) contains supplementary material, which is available to authorized users.

FUNCTIONAL MAP OF A PROFESSION: THEORY, METHODOLOGY, MODELING BASED ON COMPETENCE

The article deals with the questions of a profession functional map modeling, which includes the main objective of the profession and contains all the basic functions and function modules. The main goal of the article carried out within the framework of the grant is development of methodological recommendations on introduction of innovative approaches to the development of construction tools, methods of implementation and updating the variable part of the educational program based on a set of professional functions. The focus is on the modeling procedure of the functional maps based on competencies. The article presents some examples of modeling a functional map for the teaching profession. The practical significance of the article is that it offers the basic algorithms for modeling of functional map of the profession based on universal competencies which are basic for different levels of education.

Quasi-Steady-State Analysis based on Structural Modules and Timed Petri Net Predict System's Dynamics: The Life Cycle of the Insulin Receptor.

The insulin-dependent activation and recycling of the insulin receptor play an essential role in the regulation of the energy metabolism, leading to a special interest for pharmaceutical applications. Thus, the recycling of the insulin receptor has been intensively investigated, experimentally as well as theoretically. We developed a time-resolved, discrete model to describe stochastic dynamics and study the approximation of non-linear dynamics in the context of timed Petri nets. Additionally, using a graph-theoretical approach, we analyzed the structure of the regulatory system and demonstrated the close interrelation of structural network properties with the kinetic behavior. The transition invariants decomposed the model into overlapping subnetworks of various sizes, which represent basic functional modules. Moreover, we computed the quasi-steady states of these subnetworks and demonstrated that they are fundamental to understand the dynamic behavior of the system. The Petri net approach confirms the experimental results of insulin-stimulated degradation of the insulin receptor, which represents a common feature of insulin-resistant, hyperinsulinaemic states.

A Management System about Prevention and Maintenance for Construction Equipment

With the increasing expansion of the function of modern architecture, the huge construction equipment system’s daily management and maintenance are faced with the problem of high input and high consumption. It is an inevitable trend of modern architecture’s developing that we expand the maintenance management system. In this paper, we set up a management system of prevention and maintenance for construction equipment which include the basic framework, process and functional modules, which could achieve the prevention, maintenance and management on the basis of the device’s fault then greatly improve the level of equipment’s maintenance and management. Construction equipment is a combination of the facilities and equipment which is installed in the buildings, provide convenience, comforts and safety for people’s residing, living, and working. It usually include water supply and drainage system, ventilation and air conditioning system, electrical lighting system, fire controlling and security system, heat addition system and elevator system, etc. It is an important part of civil construction, its role in building is equivalent of the circulatory system and nervous system of human’s body. The architecture’s function of modern society has gone way beyond the scope of wind and rain, the demand of comfort, health, convenience and safety makes the modern architecture marching towards the direction of intelligent zing and automation, then the system of construction equipment becomes larger and more complex. The daily maintenance and repairment of construction equipment turns into a job of high consumption and input in the modern construction’s management.

The physics of bacterial decision making.

The choice that bacteria make between sporulation and competence when subjected to stress provides a prototypical example of collective cell fate determination that is stochastic on the individual cell level, yet predictable (deterministic) on the population level. This collective decision is performed by an elaborated gene network. Considerable effort has been devoted to simplify its complexity by taking physics approaches to untangle the basic functional modules that are integrated to form the complete network: (1) A stochastic switch whose transition probability is controlled by two order parameters—population density and internal/external stress. (2) An adaptable timer whose clock rate is normalized by the same two previous order parameters. (3) Sensing units which measure population density and external stress. (4) A communication module that exchanges information about the cells' internal stress levels. (5) An oscillating gate of the stochastic switch which is regulated by the timer. The unique circuit architecture of the gate allows special dynamics and noise management features. The gate opens a window of opportunity in time for competence transitions, during which the circuit generates oscillations that are translated into a chain of short intervals with high transition probability. In addition, the unique architecture of the gate allows filtering of external noise and robustness against variations in circuit parameters and internal noise. We illustrate that a physics approach can be very valuable in investigating the decision process and in identifying its general principles. We also show that both cell-cell variability and noise have important functional roles in the collectively controlled individual decisions.

Design and application of core mineral spectrometer

Core mineral spectrometer is one of the advanced and important tools for core digitalization, altered mineral mapping, ore deposits exploring, and ore-searching in surrounding mine and beneficiation process. In this letter, a new core mineral spectrometer (CMS 350) is designed and developed. The basic principle, structural design, function module, key components, data acquisition, and processing methods of CMS 350 are introduced. In addition, some applications and results of CMS 350 in Zijin Mining are presented to validate the performance of CMS 350.

Rational design of a biosensor circuit with semi‐log dose‐response function in Escherichia coli

A central goal of synthetic biology is to apply successful principles that have been developed in electronic and chemical engineering to construct basic biological functional modules, and through rational design, to build synthetic biological systems with predetermined functions. Here, we apply the reverse engineering design principle of biological networks to synthesize a gene circuit that executes semi‐log dose‐response, a logarithmically linear sensing function, in Escherichia coli cells. We first mathematically define the object function semi‐log dose‐response, and then search for tri‐node network topologies that can most robustly execute the object function. The simplest topology, transcriptional coherent feed‐forward loop (TCFL), among the searching results is mathematically analyzed; we find that, in TCFL topology, the semi‐log dose‐response function arises from the additive effect of logarithmical linearity intervals of Hill functions. TCFL is then genetically implemented in E. coli as a logarithmically linear sensing biosensor for heavy metal ions [mercury (II)]. Functional characterization shows that this rationally designed biosensor circuit works as expected. Through this study we demonstrated the potential application of biological network reverse engineering to broaden the computational power of synthetic biology.

A Study on the Construction of Semi-structured Electronic Medical Records Based on Clinical Pathways

AbstractTo explore the basic idea, flow and functional modules in the construction of a semi-structured electronic medical record (EMR) based on a clinical pathway (CP), and to evaluate both the effects of its implementation and the existing problems. The adoption of a semi-structured EMR favors promoting the CP management, improving the medical quality, standardizing the medical behavior, and reducing the medical cost. Considering the great and far-reaching significance in constructing a semi-structured EMR based on CP, we should increase the coverage of diseases implementing CP and rapidly develop a patient-centered, novel, semi-structured EMR at the same time.

Design and Implementation of the Personalized Search Engine Based on the Improved Behavior of User Browsing

An improved user profile based on the user browsing behavior is proposed in this study. In the user profile, the user browsing web pages behaviors, the level of interest to keywords, the user's short-term interest and long-term interest are overall taken into account. The improved user profile based on the user browsing behavior is embedded in the personalized search engine system. The basic framework and the basic functional modules of the system are described detailed in this study. A demonstration system of IUBPSES is developed in the .NET platform. The results of the simulation experiments indicate that the retrieval effects which use the IUBPSES based on the improved user profile for information search surpass the current mainstream search engines. The direction of improvement and further research is proposed in the finally.

Thalamic Network Oscillations Synchronize Ontogenetic Columns in the Newborn Rat Barrel Cortex

Neocortical areas are organized in columns, which form the basic structural and functional modules of intracortical information processing. Using voltage-sensitive dye imaging and simultaneous multi-channel extracellular recordings in the barrel cortex of newborn rats in vivo, we found that spontaneously occurring and whisker stimulation-induced gamma bursts followed by longer lasting spindle bursts were topographically organized in functional cortical columns already at the day of birth. Gamma bursts synchronized a cortical network of 300-400 µm in diameter and were coherent with gamma activity recorded simultaneously in the thalamic ventral posterior medial (VPM) nucleus. Cortical gamma bursts could be elicited by focal electrical stimulation of the VPM. Whisker stimulation-induced spindle and gamma bursts and the majority of spontaneously occurring events were profoundly reduced by the local inactivation of the VPM, indicating that the thalamus is important to generate these activity patterns. Furthermore, inactivation of the barrel cortex with lidocaine reduced the gamma activity in the thalamus, suggesting that a cortico-thalamic feedback loop modulates this early thalamic network activity.

Tyrosine phosphorylation and liver regeneration: A glance at intracellular transducers

AbstractLiver regeneration (LR) is a compensatory growth that occurs in response to resection or injury of the liver aimed at restoring the liver mass and maintaining body homeostasis. The activation of intracellular signaling pathways due to extracellular stimuli mainly reflects a highly coordinated spatial and temporal organization of phosphotyrosine‐based signals generated by the concerted action of three basic functional modules, namely protein tyrosine kinases, protein tyrosine phosphatases, and the Src homology 2 (SH2) domain. In this review, we have selected a set of signaling proteins downstream of activated cytokine and growth factor receptors that highlight the multifaceted aspects of tyrosine phosphorylation with their impact on the course of LR. Besides being a process of remarkable biological interest, LR has recently emerged as a model for dissecting molecular mechanisms underlying diverse pathophysiological states, offering new perspectives in primarily, but not only, managing life‐threatening liver diseases. © 2011 IUBMB IUBMB Life, 2011

Tyrosine phosphorylation and liver regeneration: A glance at intracellular transducers

Liver regeneration (LR) is a compensatory growth that occurs in response to resection or injury of the liver aimed at restoring the liver mass and maintaining body homeostasis. The activation of intracellular signaling pathways due to extracellular stimuli mainly reflects a highly coordinated spatial and temporal organization of phosphotyrosine-based signals generated by the concerted action of three basic functional modules, namely protein tyrosine kinases, protein tyrosine phosphatases, and the Src homology 2 (SH2) domain. In this review, we have selected a set of signaling proteins downstream of activated cytokine and growth factor receptors that highlight the multifaceted aspects of tyrosine phosphorylation with their impact on the course of LR. Besides being a process of remarkable biological interest, LR has recently emerged as a model for dissecting molecular mechanisms underlying diverse pathophysiological states, offering new perspectives in primarily, but not only, managing life-threatening liver diseases.

Analysis of New Developments and Key Technologies of Autonomous Underwater Vehicle in Marine Survey

Abstract The paper illustrates some marine survey AUVs plus their features and typical configurations, and analyzes their key technologies through classification and analysis, which are currently existed or under development. Their composition can be divided into basic modules and functional modules. Basic modules include central processing system, propeller system, power supply system and navigation system etc. Meanwhile, functional modules refer to auxiliary sensor and survey equipment. As for AUV applied in marine survey, designer should pay more consideration to the running state in high velocity flow and strengthen the control of side thrust. The configurations of marine survey AUVs from companies like Kongsberg in Norway, Hydroid in U.S., Bluefin Robotics in U.S. and Hafmynd in Iceland are analyzed and classified. The research and development process of domestic AUV are also be reviewed. As AUV can collect data with highly efficiency and better quality, it will replace traditional means of surface vessels with towed systems for its portability. Easy use of AUV can significantly reduce fuel consumption of ships, which will be widely used in marine survey in the future as a cost-effective method.

System Design of a Trusted SoC and Detailed Analysis of its Secure State Transitions

According to the relevant criterion and principle for designing and evaluating various trusted computing chips, we have proposed a new trusted SoC chip, and have given the implementation of its basic functional modules. In detail, we have discussed the design of the trusted SoC security architecture and the main module functional modules such as microprocessor, cryptographic function module, security management module, input/output interface, along with the most important memory management unit. Moreover, we have discussed reliability of relevant parameters and transfer strategy for trusted root in chip development and application, together with the simulation and validation of corresponding functions. At last, we point out that one of the most important further research directions is the trusted measurement of dynamic data and software running in security environment.

Evolution of Protein Phosphorylation for Distinct Functional Modules in Vertebrate Genomes

Recent publications have revealed that the evolution of phosphosites is influenced by the local protein structures and whether the phosphosites have characterized functions or not. With knowledge of the wide functional range of phosphorylation, we attempted to clarify whether the evolutionary conservation of phosphosites is different among distinct functional modules. We grouped the phosphosites in the human genome into the modules according to the functional categories of KEGG (Kyoto Encyclopedia of Genes and Genomes) and investigated their evolutionary conservation in vertebrate genomes from mouse to zebrafish. We have found that the phosphosites in the vertebrate-specific functional modules (VFMs), such as cellular signaling processes and responses to stimuli, are evolutionarily more conserved than those in the basic functional modules (BFMs), such as metabolic and genetic processes. The phosphosites in the VFMs are also significantly more conserved than their flanking regions, whereas those in the BFMs are not. These results hold for both serine/threonine and tyrosine residues, although the fraction of phosphorylated tyrosine residues is increased in the VFMs. Moreover, the difference in the evolutionary conservation of the phosphosites between the VFMs and BFMs could not be explained by the difference in the local protein structures. There is also a higher fraction of phosphosites with known functions in the VFMs than BFMs. Based on these findings, we have concluded that protein phosphorylation may play more dominant roles for the VFMs than BFMs during the vertebrate evolution. As phosphorylation is a quite rapid biological reaction, the VFMs that quickly respond to outer stimuli and inner signals might heavily depend on this regulatory mechanism. Our results imply that phosphorylation may have an essential role in the evolution of vertebrates.

PROMETHEUS: Technology for rapid development of biological databases

PROMETHEUS toolkit was created for rapid development of databases and provides one with convenient tools for data management. The main advantage is the capability to develop a database with visual interfaces in MVC style. Toolkit features are directly accessible by the researcher with minimal involvement of IT specialists. A set of ready-to-use system components provides functionality of adaptation the toolkit for different knowledge domains. Using embedded data drivers system engine could access to existing information sources. Convenient extensions for technologies basic functional modules are also available.

An Approach to Formally Modeling and Verifying Distributed Real-time Embedded Software

As computer systems become increasingly inter-networked, Distributed Real-time Embedded (DRE) systems has became increasingly common and important, a challenging problem faced by researchers and developers of DRE software is devising and implementing an method that can effectively analyze requirements in varying operational conditions. In this paper, a Hierarchical Distributed Real-time Embedded net (HDRE-net) is proposed as software analysis tool. The basic task, function module and communication process are modeled by using HDRE-net, thus forming the whole application through the synthesis operation of Petri net. Time Reachability Graph is adopted to analyze the correctness of HDRE-net, the basic properties of DRE software are also considered. Finally, a specific example is given to simulate the analysis process, and the results show that the method can be a good solution to analyze DRE software.

Production line simulation using STPN for maintenance scheduling

As the complexity of manufacturing systems keeps escalating, the maintenance decision making becomes increasingly challenging. Simulation has become an effective way to avoid costly decisions through what-if analysis of different maintenance policies, and maintenance schedules before their actual implementation. In this paper, a new modularized simulation package for manufacturing production systems has been developed using standard Stochastic Timed Petri-Nets (STPNs). By utilizing the basic functional modules, we can quickly build production lines with different configurations and maintenance policies. A maintenance decision support tool has also been developed in this paper, together with the simulation package, to provide offline and online maintenance decision support. Copyright © 2007 IFAC.

Adaptive Resource Management Platform for Reconfigurable Networks

Users' expectations towards technology, in terms of quality, service availability and accessibility are ever increasing. Aligned with this, the wireless world is rapidly moving towards the next generation of systems, featuring cooperating and reconfiguring capabilities for coexisting (and upcoming) Radio Access Technologies (RATs), so that to improve connectivity and reduce costs. In this respect, conventional planning and management techniques ought to be replaced by advanced schemes that consider multidimensional characteristics, increased complexity and high speeds. To this effect, means are needed capable to support scalability and to cater for advanced service features, provided to users at high rates and cost-effectively. This article provides a scheme to optimize resource management in future systems, by describing a platform that accommodates engineering mechanisms that deal with dynamic, demand driven planning and managing of spectrum and radio resources in reconfigurable networks. To do so, it first discusses the fundamentals and the approach followed in the proposed architecture and then investigates the basic functional modules. The architecture is validated through a set of use-cases that exemplify the operational applicability and efficiency in a wide range of communication scenarios.