COMPUTER-AIDED LAYOUT INTERCONNECTION EXTRACTION OF CELL-STRUCTURED INTEGRATED CIRCUIT MASKS

The program CELLINEX presented in the paper finds the cellular interconnections from the layout of cell-structured integrated circuits. From this the logical description of the circuit is generated and it is checked whether the realized interconnections are permitted or not and whether there are trivial lacks or not. The paper describes the characteristics of the program and the most important algorithms. Some kinds of documentation of the results are presented

Magyar Tanítóképző 55 (1942) 5

Magyar Tanítóképző A Tanítóképző-intézeti Tanárok Országos Egyesületének folyóirata 55. évfolyam, 5. szám Budapest, 1942. máju

SignaLink 2 - a signaling pathway resource with multi-layered regulatory networks

ABSTRACT: BACKGROUND: Signaling networks in eukaryotes are made up of upstream and downstream subnetworks. The upstream subnetwork contains the intertwined network of signaling pathways, while the downstream regulatory part contains transcription factors and their binding sites on the DNA as well as microRNAs and their mRNA targets. Currently, most signaling and regulatory databases contain only a subsection of this network, making comprehensive analyses highly time-consuming and dependent on specific data handling expertise. The need for detailed mapping of signaling systems is also supported by the fact that several drug development failures were caused by undiscovered cross-talk or regulatory effects of drug targets. We previously created a uniformly curated signaling pathway resource, SignaLink, to facilitate the analysis of pathway cross-talks. Here, we present SignaLink 2, which significantly extends the coverage and applications of its predecessor.Description: We developed a novel concept to integrate and utilize different subsections (i.e., layers) of the signaling network. The multi-layered (onion-like) database structure is made up of signaling pathways, their pathway regulators (e.g., scaffold and endocytotic proteins) and modifier enzymes (e.g., phosphatases, ubiquitin ligases), as well as transcriptional and post-transcriptional regulators of all of these components. The user-friendly website allows the interactive exploration of how each signaling protein is regulated. The customizable download page enables the analysis of any user-specified part of the signaling network. Compared to other signaling resources, distinctive features of SignaLink 2 are the following: 1) it involves experimental data not only from humans but from two invertebrate model organisms, C. elegans and D. melanogaster; 2) combines manual curation with large-scale datasets; 3) provides confidence scores for each interaction; 4) operates a customizable download page with multiple file formats (e.g., BioPAX, Cytoscape, SBML). Non-profit users can access SignaLink 2 free of charge at http://SignaLink.org CONCLUSIONS: With SignaLink 2 as a single resource, users can effectively analyze signaling pathways, scaffold proteins, modifier enzymes, transcription factors and miRNAs that are important in the regulation of signaling processes. This integrated resource allows the systems-level examination of how cross-talks and signaling flow are regulated, as well as provide data for cross-species comparisons and drug discovery analyses

SignaLink 2 - a signaling pathway resource with multi-layered regulatory networks.

BACKGROUND Signaling networks in eukaryotes are made up of upstream and downstream subnetworks. The upstream subnetwork contains the intertwined network of signaling pathways, while the downstream regulatory part contains transcription factors and their binding sites on the DNA as well as microRNAs and their mRNA targets. Currently, most signaling and regulatory databases contain only a subsection of this network, making comprehensive analyses highly time-consuming and dependent on specific data handling expertise. The need for detailed mapping of signaling systems is also supported by the fact that several drug development failures were caused by undiscovered cross-talk or regulatory effects of drug targets. We previously created a uniformly curated signaling pathway resource, SignaLink, to facilitate the analysis of pathway cross-talks. Here, we present SignaLink 2, which significantly extends the coverage and applications of its predecessor. DESCRIPTION We developed a novel concept to integrate and utilize different subsections (i.e., layers) of the signaling network. The multi-layered (onion-like) database structure is made up of signaling pathways, their pathway regulators (e.g., scaffold and endocytotic proteins) and modifier enzymes (e.g., phosphatases, ubiquitin ligases), as well as transcriptional and post-transcriptional regulators of all of these components. The user-friendly website allows the interactive exploration of how each signaling protein is regulated. The customizable download page enables the analysis of any user-specified part of the signaling network. Compared to other signaling resources, distinctive features of SignaLink 2 are the following: 1) it involves experimental data not only from humans but from two invertebrate model organisms, C. elegans and D. melanogaster; 2) combines manual curation with large-scale datasets; 3) provides confidence scores for each interaction; 4) operates a customizable download page with multiple file formats (e.g., BioPAX, Cytoscape, SBML). Non-profit users can access SignaLink 2 free of charge at http://SignaLink.org. CONCLUSIONS With SignaLink 2 as a single resource, users can effectively analyze signaling pathways, scaffold proteins, modifier enzymes, transcription factors and miRNAs that are important in the regulation of signaling processes. This integrated resource allows the systems-level examination of how cross-talks and signaling flow are regulated, as well as provide data for cross-species comparisons and drug discovery analyses

sysbio-curie/exact-stoch-log-mod

A MATLAB toolbox for the exact calculation of stationary states + parameter sensitivity analysis & fitting of stochastic logical models

A tartós intenzív műtrágyázás utóhatásai a növényi szárazanyag elemösszetételére

Borsó és napraforgó jelzőnövényekkel, 1 kg talajt tartalmazó edényekben végeztünk tenyészedény-kísérletet az 1970-es évek elején, az intenzív műtrágyahasználat kezdetén vett és tárolt talajmintákkal, valamint 30 év elteltével ugyanazokról a helyekről gyűjtött párjukkal. A minták karbonátos talajok (csernozjomok) esetén 6, nem karbonátos talajok (savanyú barna erdőtalajok) esetén pedig 13 mintavételi körzetet reprezentáltak. A virágzásig nevelt növények mintáit elhamvasztottuk és megmértük a P-, K-, Ca-, Mg-, Na- és B-tartalmukat. Korábbi talajvizsgálati adatainkkal egyezően, a savanyú talajokon termesztett növényminták szárazanyagában igen jelentős B-tartalom csökkenés volt mérhető. A mostanra kialakult és vélhetően állandósult helyzetben a savanyú talajokon termesztett növények B-tartalma most már lényegesen kisebb, mint a karbonátos talajokon termesztetteké. Az ebből adódó estleges egészségügyi hatások vizsgálata indokolt lenne. A növények P-tartalma is növekedett, követve a talaj oldható P-tartalmának változását. Ez felveti annak a nagy valószínűségét, hogy jelenleg és még sokáig a növények Zn és más P-antagonista mikroelem-tartalma tartósan alacsony marad. A K-műtrágyázás olyan módon csökkentette a növényi szárazanyag Mg-, Ca- és Na-tartalmát, hogy emellett a növények K-koncentrációja nem minden esetben követte a talajok nagyobb K-ellátottságát. Vizsgálataink szerint tehát a tartós intenzív műtrágyázás hatására lényegesen megváltozott a termesztett növények elemösszetétele, ami a hosszú utóhatás időszakra is állandósult. A változásoknak táplálkozás-egészségügyi hatásai is lehetnek. | An experiment was performed on pea and sunflower in pots containing 1 kg soil, either taken and stored in the early 1970s, when intensive mineral fertilization was first introduced in Hungary, or taken 30 years later from the same locations. Calcareous (chernozem) soil samples were taken from 6 different sampling sites, while non-calcareous (acidic brown forest) soils were represented by samples from 13 different locations. Samples of plants grown to flowering were ashed and the phosphorus, potassium, calcium, magnesium, sodium and boron contents were recorded. As it was predicted by earlier soil analyses, there was a very substantial decline in the boron content of plants grown on acidic soils. Consequently, it can now be expected that the boron content of plants grown on acidic soils will be much lower than for those grown on calcareous soils. The possible heath effects of this warrant investigation. There was also an increase in the phosphorus content of the plants, in line with changes in the soluble soil phosphorus, making it highly probable that the plants will have low contents of zinc and of other P-antagonistic trace elements for a long time. In response to potassium fertilization the magnesium, calcium and sodium contents of the plants decreased, while an elevated soluble soil potassium did not always result in higher potassium contents in the plants. The results thus indicated that long-term intensive fertilization caused considerable changes in the element composition of the plants and that these changes remained constant over a long period of after-effects. These changes might have consequences for human health

Exact solving and sensitivity analysis of stochastic continuous time Boolean models

International audienceBackground: Solutions to stochastic Boolean models are usually estimated by Monte Carlo simulations, but as the state space of these models can be enormous, there is an inherent uncertainty about the accuracy of Monte Carlo estimates and whether simulations have reached all attractors. Moreover, these models have timescale parameters (transition rates) that the probability values of stationary solutions depend on in complex ways, raising the necessity of parameter sensitivity analysis. We address these two issues by an exact calculation method for this class of models. Results: We show that the stationary probability values of the attractors of stochastic (asynchronous) continuous time Boolean models can be exactly calculated. The calculation does not require Monte Carlo simulations, instead it uses graph theoretical and matrix calculation methods previously applied in the context of chemical kinetics. In this version of the asynchronous updating framework the states of a logical model define a continuous time Markov chain and for a given initial condition the stationary solution is fully defined by the right and left nullspace of the master equation's kinetic matrix. We use topological sorting of the state transition graph and the dependencies between the nullspaces and the kinetic matrix to derive the stationary solution without simulations. We apply this calculation to several published Boolean models to analyze the under-explored question of the effect of transition rates on the stationary solutions and show they can be sensitive to parameter changes. The analysis distinguishes processes robust or, alternatively, sensitive to parameter values, providing both methodological and biological insights. Conclusion: Up to an intermediate size (the biggest model analyzed is 23 nodes) stochastic Boolean models can be efficiently solved by an exact matrix method, without using Monte Carlo simulations. Sensitivity analysis with respect to the model's timescale parameters often reveals a small subset of all parameters that primarily determine the stationary probability of attractor states