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PubMed2000

Primary sequence and enzymic properties of two modular endoglucanases, Cel5A and Cel45A, from the anaerobic fungus Piromyces equi.

Two endoglucanase cDNAs, designated cel5A and cel45A, were isolated from a cDNA library of the anaerobic fungus Piromyces equi. Sequence analysis revealed that cel5A has an open reading frame of 5142 bp and encodes a 1714 amino acid modular enzyme, Cel5A, with a molecular mass of 194847 Da. Cel5A consists of four catalytic domains homologous to family-5 glycosyl hydrolases, two C-terminal dockerins and one N-terminal dockerin. This is the first report of a complete gene containing tandem repeats of family-5 catalytic domains. The cDNA cel45A has an open reading frame of 1233 bp and encodes a 410 amino acid modular enzyme, Cel45A, with a molecular mass of 44380 Da. The catalytic domain, located at the C terminus, is homologous to the family-45 glycosyl hydrolases. Cel45A is the first family-45 enzyme to be described in an anaerobe. The presence of dockerins at the N and C termini of Cel5A and at the N terminus of Cel45A implies that both enzymes are part of the high-molecular-mass cellulose-degrading complex produced by Piromyces equi. The catalytic domain nearest the C terminus of Cel5A and the catalytic domain of Cel45A were hyperexpressed as thioredoxin fusion proteins, Trx-Cel5A' and Trx-Cel45A', and subjected to biochemical analysis. Trx-Cel5A' has a broad substrate range, showing activity against carboxymethylcellulose, acid-swollen cellulose, barley beta-glucan, lichenin, carob galactomannan, p-nitrophenyl beta-D-cellobiopyranoside and xylan. Trx-Cel45A' is active against carboxymethylcellulose, acid-swollen cellulose and the mixed linkage glucans, barley beta-glucan and lichenin.

Amino Acid Sequence↗
PubMed2006

Amplification generates modular diversity at an avirulence locus in the pathogen Phytophthora.

The destructive late blight pathogen Phytophthora infestans is notorious for its rapid adaptation to circumvent detection mediated by plant resistance (R) genes. We performed comparative genomic hybridization on microarrays (array-CGH) in a near genome-wide survey to identify genome rearrangements related to changes in virulence. Six loci with copy number variation were found, one of which involves an amplification colocalizing with a previously identified locus that confers avirulence in combination with either R gene R3b, R10, or R11. Besides array-CGH, we used three independent approaches to find candidate genes at the Avr3b-Avr10-Avr11 locus: positional cloning, cDNA-AFLP analysis, and Affymetrix array expression profiling. This resulted in one candidate, pi3.4, that encodes a protein of 1956 amino acids with regulatory domains characteristic for transcription factors. Amplification is restricted to the 3' end of the full-length gene but the amplified copies still contain the hallmarks of a regulatory protein. Sequence comparison showed that the amplification may generate modular diversity and assist in the assembly of novel full-length genes via unequal crossing-over. Analyses of P. infestans field isolates revealed that the pi3.4 amplification correlates with avirulence; isolates virulent on R3b, R10, and R11 plants lack the amplified gene cluster. The ancestral state of 3.4 in the Phytophthora lineage is a full-length, single-copy gene. In P. infestans, however, pi3.4 is a dynamic gene that is amplified and has moved to other locations. Modular diversity could be a novel mechanism for pathogens to quickly adapt to changes in the environment.

Chromosomes, Artificial, Bacterial↗
PubMed1990

Construction of modular circuits in the mammalian brain.

Comparison of seemingly different modular units in the mammalian brain raises the possibility of a common mechanism for their formation: the growth of neuropil mediated by trophic interactions. The ongoing postnatal construction of modular circuits according to trophic interplay may in turn account for the remarkable plasticity of the juvenile brain. By the same token, the normal waning of circuit construction during postnatal development may explain the end of critical periods, the diminished ability to recover from injury in older animals, and the decline with increasing age in the ability of mammals to learn complex skills.

Animals↗
PubMed2005

Modular synchronization in complex networks.

We study the synchronization transition (ST) of a modified Kuramoto model on two different types of modular complex networks. It is found that the ST depends on the type of intermodular connections. For the network with decentralized (centralized) intermodular connections, the ST occurs at finite coupling constant (behaves abnormally). Such distinct features are found in the yeast protein interaction network and the Internet, respectively. Moreover, by applying the finite-size scaling analysis to an artificial network with decentralized intermodular connections, we obtain the exponent associated with the order parameter of the ST to be beta approximately 1 different from beta(MF) approximately 1/2 obtained from the scale-free network with the same degree distribution but the absence of modular structure, corresponding to the mean field value.

Journal Article↗
PubMed2006

Information propagation on modular networks.

Networks with a community (or modular) structure underlie many social and biological phenomena. In such a network individuals tend to form sparsely linked local communities, each having dense internal connections. We investigate the dynamics of information propagation on modular networks by using a three-state epidemic model with a unit spreading rate (i.e., the probability for a susceptible individual to be "infected" with the information is one). We find a surprising, resonancelike phenomenon: the information lifetime on the network can be maximized by the number of modules. The result can be useful for optimizing or controlling information spread on social or biological networks.

Journal Article↗
PubMed2006

Growth model for complex networks with hierarchical and modular structures.

A hierarchical and modular network model is suggested by adding a growth rule along with the preferential attachment (PA) rule into Motter's modeling procedure. The proposed model has an increasing number of vertices but a fixed number of modules and hierarchical levels. The vertices form lowest-level modules which in turn constitute higher-level modules hierarchically. The creation of connections between two vertices in a single module or in two different modules of the same level obeys the PA rule. The structural characteristics of this model are investigated analytically and numerically. The results show that the degree distribution, the module size distribution, and the clustering function of the model possess a power-law property which is similar to that in many real-world networks. The model is then used to predict the growth trends of real-world networks with modular and hierarchical structures. By comparing this model with those real-world networks, an interesting conclusion is found: that many real-world networks are in their early stages of development, and when the growth time is large enough, the modules and levels of the networks will be ultimately merged.

Journal Article↗
PubMed1996

Modular nature of abscisic acid (ABA) response complexes: composite promoter units that are necessary and sufficient for ABA induction of gene expression in barley.

The modular nature of the abscisic acid response complex (ABRC), the promoter unit necessary and sufficient for abscisic acid (ABA) induction of gene expression in barley, is defined in this study. We investigated ABA induction of a barley late embrogenesis abundant (Lea) gene, HVA1, and found that the ABRC of this gene consists of a 10-bp box with an ACGT core (ACGT-box) and the 11 bp directly upstream, named coupling element 3 (CE3). Only one copy of this ABRC is sufficient to confer ABA induction when linked to a minimal promoter. Because we previously reported another ABRC in the barley HVA22 gene, which consists of an ACGT-box with a distal coupling element (CE1), exchange experiments were conducted to study the interaction among modular elements in these ABRCs. We show that ACGT-boxes in these ABRCs are interchangeable, indicating that an ACGT-box can interact with either a distal or a proximal coupling element to confer ABA response. However, the two coupling elements are not fully exchangeable. Although CE3 can function either proximal or distal to the ACGT-box, CE1 is only functional at the distal position. The presence of both the distal and the proximal coupling elements has a synergistic effect on the absolute level of expression as well as on ABA induction. These ABRCs function in both seed and vegetative tissues. In seeds, ABA induction of the ABRC containing the proximal CE3, but not the ABRC with the distal CE1, is enhanced in the presence of the transcription regulator Viviparous1, indicating that these two ABRCs are mediated by different ABA signal transduction pathways.

Abscisic Acid↗
PubMed2004

Massively parallel classification of single-trial EEG signals using a min-max modular neural network.

This paper presents a method for classifying single-trial electroencephalogram (EEG) signals using min-max modular neural networks implemented in a massively parallel way. The method has three main steps. First, a large-scale, complex EEG classification problem is simply divided into a reasonable number of two-class subproblems, as small as needed. Second, the two-class subproblems are simply learned by individual smaller network modules in parallel. Finally, all the individual trained network modules are integrated into a hierarchical, parallel, and modular classifier according to two module combination laws. To demonstrate the effectiveness of the method, we perform simulations on fifteen different four-class EEG classification tasks, each of which consists of 1491 training and 636 test data. These EEG classification tasks were created using a set of non-averaged, single-trial hippocampal EEG signals recorded from rats; the features of the EEG signals are extracted using wavelet transform techniques. The experimental results indicate that the proposed method has several attractive features. 1) The method is appreciably faster than the existing approach that is based on conventional multilayer perceptrons. 2) Complete learning of complex EEG classification problems can be easily realized, and better generalization performance can be achieved. 3) The method scales up to large-scale, complex EEG classification problems.

Algorithms↗
PubMed2004

Modular fuzzy-reinforcement learning approach with internal model capabilities for multiagent systems.

To date, many researchers have proposed various methods to improve the learning ability in multiagent systems. However, most of these studies are not appropriate to more complex multiagent learning problems because the state space of each learning agent grows exponentially in terms of the number of partners present in the environment. Modeling other learning agents present in the domain as part of the state of the environment is not a realistic approach. In this paper, we combine advantages of the modular approach, fuzzy logic and the internal model in a single novel multiagent system architecture. The architecture is based on a fuzzy modular approach whose rule base is partitioned into several different modules. Each module deals with a particular agent in the environment and maps the input fuzzy sets to the action Q-values; these represent the state space of each learning module and the action space, respectively. Each module also uses an internal model table to estimate actions of the other agents. Finally, we investigate the integration of a parallel update method with the proposed architecture. Experimental results obtained on two different environments of a well-known pursuit domain show the effectiveness and robustness of the proposed multiagent architecture and learning approach.

Journal Article↗
PubMed2003

On the structural and functional modularity of glycinamide ribonucleotide formyltransferases.

Glycinamide ribonucleotide formyltransferases (GARTs) are part of the de novo purine biosynthetic pathway, catalyzing the direct transfer of a formyl group from the tetrahydrofolate cofactor to the glycinamide ribonucleotide substrate. Despite the low amino acid-sequence identity between the GARTs from Escherichia coli and human, their tertiary structures are superimposable. As part of our functional studies of these enzymes, we have investigated the interchangeability of individual protein fragments or modules between the two enzymes and the functional properties of the resulting hybrids. The modular nature of GART facilitated the creation of combinatorial libraries of chimeras between the Escherichia coli and human enzymes, which were functionally selected through complementation of an auxotrophic Escherichia coli strain. From a pool of several dozen sequence distinct hybrids, six in vivo-functional fusion genes were selected, overexpressed, and purified to homogeneity. The kinetic analysis of these constructs and the comparison of their k(cat) and K(M) values to the parental enzymes suggest that the characteristic kinetic properties from the two parents are "modular encoded" and can be exchanged by domain swapping. The chimeras in general, however, are subject to temperature instability and misfolding; thus, they serve primarily as useful candidates for further rounds of optimization.

Catalysis↗
PubMed2001

New tools for studying integration and modularity.

The study of phenotypic integration concerns the modular nature of organismal phenotypes. The concept provides a rationale for why certain subsets of phenotypic traits show particularly high levels of association over development and/or evolution. The techniques detailed in this report facilitate the generation and testing of hypotheses of phenotypic integration and trait interaction. The approach advocated for exploring patterns of interaction among traits is based on the statistical notion of conditional independence, incorporated in a technique known as graphical modeling. The use of graphical models is illustrated with an application to a well-known biological dataset of fowl skeletal measurements, previously analyzed by Sewall Wright. A definition of phenotypic modularity is given, based on a notion of mutual information, which provides a consistent criterion for recognizing and delimiting integrated subsets of traits and which can be related to standard models of multivariate selection.

Analysis of Variance↗
PubMed1975

The Denver universal microspectroradiometer (DUM). II. Computer configuration and modular programming for radiometry.

This paper describes and discusses for microscopists and spectroscopists the choice of computer equipment and the design of programs used in the Denver Universal Microspectroradiometer (DUM). This instrument is an accurate computerized photon-counting microspectrophotometer, microspectrofluorimeter and microrefractometer. The computer is used to control the operation of the system, to acquire radiometric data of various kinds, and to reduce, analyse and output the data in a readily usable form. Since the radiometer was designed to carry out many kinds of measurements in a variety of micro- and macroscopic specimens, and since different methods of microscopy or spectroscopy have to be combined in various ways fro the study of any one specimen, no single master-program could fulfill efficiently all foreseeable requirements. Therefore, the programming developed is interactive, modular, hierarchical and hybrid. Modular interactive programming makes it possible for almost any kind of main program, applicable to almost any kind of measurement, to be assembled quickly from a collection of hierarchical subroutines. Main programs are short and composed mainly of Fortran statements calling subroutines; subroutines, in turn, automatically call other subroutines over many levels. The subroutines are independently written and optimized for maximum operational efficiency in the computer system used, or for maximum ease of transfer to other systems. This approach to programming enables someone unfamiliar with computer languages to operate the radiometric system from the console of the CRT terminal. The writing of new main programs, by linking groups of existing subroutines, requires only a minimum acquaintance with Fortran; only the writing and revision of subroutines requires programming experience. Differences and similarities in the method of computer operation between the present system and other computerized radiometers are briefly discussed.

Computers↗
PubMed1996

A secreted protein tyrosine phosphatase with modular effector domains in the bacterial pathogen Salmonella typhimurium.

A number of bacterial pathogens have evolved sophisticated strategies to subvert host-cell signal-transduction pathways for their own benefit. These bacteria produce and export proteins capable of specific interactions with key mammalian cell regulatory molecules in order to derail the normal functions of the cells. In this study, we describe the identification of a modular effector protein secreted by the bacterial pathogen Salmonella typhimurium that is required for its full display of virulence. Sequence analysis revealed that a carboxy-terminal region of this protein, which we have termed SptP, is homologous to the catalytic domains of protein tyrosine phosphatases. Purified SptP protein efficiently dephosphorylated peptide substrates phosphorylated on tyrosine. An engineered mutant of SptP in which a critical Cys residue in the catalytic domain was changed to Ser was devoid of phosphatase activity, indicating a catalytic mechanism similar to that of other tyrosine phosphatases. In addition, an amino-terminal region of SptP exhibited sequence similarity to the ribosyltransferase exoenzyme S from Pseudomonas aeruginosa and the cytotoxin YopE from Yersinia spp. The modular nature of this effector protein may allow multiple interactions with host-cell signalling functions.

Amino Acid Sequence↗
PubMed1993

Management of chondrosarcoma including modular ceramic and alumina prosthetic replacement.

Forty-one cases of chondrosarcoma from varying sites throughout the body, and treated exclusively by one of the authors (R.L.H.) from 1972 to 1990 were reviewed. The symptoms, signs, location of tumours, treatment and progress are presented. Particular attention was paid to modular bone replacement techniques. Excision and reconstruction of the bone or joint were carried out in 17 femora, five tibia and six humeri. Comparison between this method of management and other techniques is discussed. Titanium and alumina prostheses for the hip, femur, tibia, shoulder and humerus have been designed by the senior author. These are both inert and modular, and have been found to be superior to other methods of treatment in both function and cosmesis. They do not possess the same potential donor infection risks and other disadvantages of allograft replacement. Immediate postoperative weight bearing and mobilization are possible with these systems. The Huckstep prostheses allow for bony ingrowth into their porous coated alumina sleeves, spacers and stems. In addition, the titanium alloy locking component for the femoral stems has an elasticity half that of other metal alloys and this was found to minimize stress shielding.

Adult↗
PubMed1994

The functional evaluation of patients with primary malignant tumours about the knee treated by modular endoprosthetic replacement.

Between 1985 and 1992, 39 patients with primary malignant neoplasms about the knee presented to the musculoskeletal oncology service at the Royal Prince Alfred Hospital, Sydney. Twenty-eight patients met the criteria for limb salvage surgery and underwent reconstruction using a modular endoprosthetic replacement. Twenty surviving patients and the modular prosthesis were evaluated using the rating system adopted by the Musculoskeletal Tumour Society. Eighteen patients had resection of the distal femur and two had resection of the proximal tibia. The average follow up was 36.5 months (range 6-93). Overall the results were excellent in two patients, good in 16 and fair in two. The prosthesis was rated as excellent in 13, good in four, fair in two and poor in one. The complications encountered are discussed. The authors conclude that this prosthesis provides a satisfactory form of reconstruction following limb salvage surgery for tumours about the knee.

Adolescent↗
PubMed2004

Modular biased-competition and cooperation: a candidate mechanism for selective working memory.

Prefrontal cortex (PFC) has been suggested to play an important role in executive cognitive functions, participating in planning and controlling behaviour. The results of several recent electrophysiological studies indicate that PFC might be involved not only in the active maintenance of information but in doing so in a context- or task-dependent manner. In a delayed-match-to-sample paradigm, recordings from neurons in the PFC showed their ability to selectively represent information, which is needed for task completion, suggesting that task-irrelevant information does not access working memory. We present a neurodynamical computational model of a part of the PFC to account for the selective representation of information in working memory. We show that a network of biological realistic integrate-and-fire excitatory and inhibitory neurons, implementing the mechanisms of local or modular biased-competition, which is transmitted through cooperation to different subsets of neuronal pools, can explain the formation of selective context-dependent working memory. The modes of operation of the network are characterized and the corresponding parameter settings revealed. Modular competition and cooperation might constitute general mechanisms for implementing context-dependent formation of working memory.

Action Potentials↗
PubMedDate not supplied

Quantitative trait loci mapping of floral and leaf morphology traits in Arabidopsis thaliana: evidence for modular genetic architecture.

Summary Morphological variation within organisms is integrated and often modular in nature. That is to say, the size and shape of traits tend to vary in a coordinated and structured manner across sets of organs or parts of an organism. The genetic basis of this morphological integration is largely unknown. Here, we report on quantitative trait loci (QTL) analysis of leaf and floral organ size in Arabidopsis thaliana. We evaluate patterns of genetic correlations among traits and perform whole-genome scans using QTL mapping methods. We detected significant genetic variation for the size and shape of each floral and leaf trait in our study. Moreover, we found large positive genetic correlations among sets of either flower or leaf traits, but low and generally nonsignificant genetic correlations between flower and leaf traits. These results support the hypothesis of independent floral and vegetative modules. We consider co-localization of QTL for different traits as support for a pleiotropic basis of morphological integration and modularity. A total of eight QTL affecting flower and three QTL affecting leaf traits were identified. Most QTL affected either floral or leaf traits, providing a general explanation for high correlations within and low correlations between modules. Only two genomic locations affected both flower and leaf growth. These results are discussed in the context of the evolution of modules, pleiotropy, and the putative homologous relationship between leaves and flowers.

Arabidopsis↗
PubMed2006

Stem damage during implantation of modular hip prostheses.

Modular hip prostheses are commonly used today. Dedicated surgical auxiliary instrumentation is indispensable. A correct coupling between the prosthesis and the instrument is necessary to avoid damage. Based on a specific commercial design (AnCAFit, Wright Cremascoli Ortho, Toulon, France), the aim of this work was to assess if stem holders of modular prostheses can induce any stem damage, and if so, to identify the features that provide minimal damage. Two different stem holder connector designs were investigated. The surface of the stem cavity was inspected to identify the damage caused by the use of the two connectors after a simulated surgical handling. Both connectors induced some damage, with significantly more damage being caused by a supposedly improved design. Scars due to contact with the stem holder were observed on the stem cavity surface. This may be sufficient to trigger increased fretting damage during service life, causing the production of fretting debris.

Hip Prosthesis↗