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PubMed2006

A modular framework for development and interlaboratory sharing and validation of diffusion tensor tractography algorithms.

This Technical Note describes a novel modular framework for development and interlaboratory distribution and validation of 3D tractography algorithms based on in vivo diffusion tensor imaging (DTI) measurements. The proposed framework allows individual MRI research centers to benefit from new tractography algorithms developed at other independent centers by "plugging" new tractography modules directly into their own custom DTI software tools, such as existing graphical user interfaces (GUI) for visualizing brain white matter pathways. The proposed framework is based on the Java 3D programming platform, which provides an object-oriented programming (OOP) model and independence of computer hardware configuration and operating system. To demonstrate the utility of the proposed approach, a complete GUI for interactive DTI tractography was developed, along with two separate and interchangeable modules that implement two different tractography algorithms. Although the application discussed here relates to DTI tractography, the programming concepts presented here should be of interest to anyone who wishes to develop platform-independent GUI applications for interactive 3D visualization.

Algorithms↗
PubMed2006

Development and validation of a modular, extensible docking program: DOCK 5.

We report on the development and validation of a new version of DOCK. The algorithm has been rewritten in a modular format, which allows for easy implementation of new scoring functions, sampling methods and analysis tools. We validated the sampling algorithm with a test set of 114 protein-ligand complexes. Using an optimized parameter set, we are able to reproduce the crystal ligand pose to within 2 A of the crystal structure for 79% of the test cases using our rigid ligand docking algorithm with an average run time of 1 min per complex and for 72% of the test cases using our flexible ligand docking algorithm with an average run time of 5 min per complex. Finally, we perform an analysis of the docking failures in the test set and determine that the sampling algorithm is generally sufficient for the binding pose prediction problem for up to 7 rotatable bonds; i.e. 99% of the rigid ligand docking cases and 95% of the flexible ligand docking cases are sampled successfully. We point out that success rates could be improved through more advanced modeling of the receptor prior to docking and through improvement of the force field parameters, particularly for structures containing metal-based cofactors.

Algorithms↗
PubMed2005

pSAT vectors: a modular series of plasmids for autofluorescent protein tagging and expression of multiple genes in plants.

Autofluorescent protein tags represent one of the major and, perhaps, most powerful tools in modern cell biology for visualization of various cellular processes in vivo. In addition, advances in confocal microscopy and the development of autofluorescent proteins with different excitation and emission spectra allowed their simultaneous use for detection of multiple events in the same cell. Nevertheless, while autofluorescent tags are widely used in plant research, the need for a versatile and comprehensive set of vectors specifically designed for fluorescent tagging and transient and stable expression of multiple proteins in plant cells from a single plasmid has not been met by either the industrial or the academic communities. Here, we describe a new modular satellite (SAT) vector system that supports N- and C-terminal fusions to five different autofluorescent tags, EGFP, EYFP, Citrine-YFP, ECFP, and DsRed2. These vectors carry an expanded multiple cloning site that allows easy exchange of the target genes between different autofluorescence tags, and expression of the tagged proteins is controlled by constitutive promoters, which can be easily replaced with virtually any other promoter of interest. In addition, a series of SAT vectors has been adapted for high throughput Gateway recombination cloning. Furthermore, individual expression cassettes can be assembled into Agrobacterium binary plasmids, allowing efficient transient and stable expression of multiple autofluorescently tagged proteins from a single vector following its biolistic delivery or Agrobacterium-mediated genetic transformation.

Base Sequence↗
PubMed2005

Modular organization of SARS coronavirus nucleocapsid protein.

The SARS-CoV nucleocapsid (N) protein is a major antigen in severe acute respiratory syndrome. It binds to the viral RNA genome and forms the ribonucleoprotein core. The SARS-CoV N protein has also been suggested to be involved in other important functions in the viral life cycle. Here we show that the N protein consists of two non-interacting structural domains, the N-terminal RNA-binding domain (RBD) (residues 45-181) and the C-terminal dimerization domain (residues 248-365) (DD), surrounded by flexible linkers. The C-terminal domain exists exclusively as a dimer in solution. The flexible linkers are intrinsically disordered and represent potential interaction sites with other protein and protein-RNA partners. Bioinformatics reveal that other coronavirus N proteins could share the same modular organization. This study provides information on the domain structure partition of SARS-CoV N protein and insights into the differing roles of structured and disordered regions in coronavirus nucleocapsid proteins.

Amino Acid Sequence↗
PubMed1983

A modular program for analysis of electrophysiological data on a laboratory minicomputer.

In the study of electrophysiological phenomena, the signals to be investigated are often reduced to sampled time series or point processes. Nowadays, the measuring equipment frequently includes one or more micro- and/or minicomputers which perform the data acquisition (including, e.g., A-D conversion and interval measurements) and the subsequent data processing and analysis. This paper describes the structured organization of data measurement and analysis of electrophysiological data performed by a modular software program implemented on a laboratory minicomputer. The program is used in our clinical laboratory by a number of research teams with different experimental objectives. The input data structure for the program has a standardized format, comprising multiplexed data channels preceded by a 256 entry parameter block containing general processing information and specific information concerning the analyses performed. The tasks carried out by the program are the calculation of distributions and correlations, digital filtering and estimation of spectra. The program can easily be extended by writing new software modules.

Computers↗
PubMed1992

The modular architecture of vertebrate collagens.

Collagens are typical mosaic proteins containing a number of shuffled domains. These domains have been classified by sequence similarity in order to characterize their structural and functional relationships to other proteins. This analysis provides an overview of homologies of collagen domains. It also reveals two new relationships: (i) a module common to type V, IX, XI, and XII collagens was found to be homologous to the heparin binding domain of thrombospondin; (ii) the modular architecture of a human type VII collagen fragment was identified. Its N-terminal globular domain contains fibronectin type III repeats located adjacent to a Von Willebrand factor type A module. The proposed structural similarities point to analogous subfunctions of the respective domains in otherwise distinct proteins.

Amino Acid Sequence↗
PubMed1995

Divergent sequence motifs correlated with the substrate specificity of (methyl)malonyl-CoA:acyl carrier protein transacylase domains in modular polyketide synthases.

The amino acid sequences of a large number of polyketide synthase domains that catalyse the transacylation of either methylmalonyl-CoA or malonyl-CoA onto acyl carrier protein (ACP) have been compared. Regions were identified in which the acyltransferase sequences diverged according to whether they were specific for malonyl-CoA or methylmalonyl-CoA. These differences are sufficiently clear to allow unambiguous assignment of newly-sequenced acyltransferase domains in modular polyketide synthases. Comparison with the recently-determined structure of the malonyltransferase from Escherichia coli fatty acid synthase showed that the divergent region thus identified lies near the acyltransferase active site, though not close enough to make direct contact with bound substrate.

Acyl Carrier Protein↗
PubMed1995

In vitro production of monoclonal antibodies in high concentration in a new and easy to handle modular minifermenter.

This paper describes a new and easy to handle reusable minifermenter for high-density culture of hybridoma and other cells. The culture apparatus is composed of two modules: a 40 ml disposable cell culture and antibody production chamber (the 'production module') and a 550 ml medium reservoir (the 'supply module'). The two modules are separated from each other by a dialysis membrane allowing passage of low molecular mass nutrients and metabolites. The monoclonal antibodies are produced and enriched in the production module. The outer part of this module is made from a thin gas-permeable silicone rubber membrane allowing exchange of gases (oxygen and carbon dioxide). To start the culture, the cells are injected into the production module through ports in the silicone rubber which are equipped with Luer Lock connectors. Samples can be removed in the same way. For culturing, the minifermenter is rolled on a roller apparatus in a carbon dioxide-supplied incubator. Depending on the individual properties of the hybridoma cells cultured, cell densities of more than 10 x 10(6) (in some cases up to 35 x 10(6)) cells per ml and monoclonal antibody concentrations of several mg per ml can be obtained in the new minifermenter. On average, 61 mg (range: 9-159 mg) could be produced within 1-4 weeks. In terms of their properties the monoclonal antibodies produced in the new modular minifermenter were indistinguishable from antibodies prepared from ascitic fluid or from the supernatant of conventional stationary culture. The culture method is a useful alternative to the in vivo production method in mice. In addition, it represents a completely new, inexpensive and easy to handle general solution to the problem of culturing cells in high density and obtaining cellular products in high concentrations.

Antibodies, Monoclonal↗
PubMed1992

Modularity of the slit protein. Characterization of a conserved carboxy-terminal sequence in secreted proteins and a motif implicated in extracellular protein interactions.

Since our characterization of the slit cDNA sequence, encoding a protein secreted by glial cells and involved in the formation of axonal pathways in Drosophila, we have discovered that the protein contains two additional sequence motifs that are highly conserved in a variety of proteins. A search of the GenPept database with the 73 amino acids at the carboxy terminus of slit revealed that this region contains significant similarity to a carboxy-terminal domain found in six other exported proteins. This observation has allowed us to define a new carboxy-terminal protein motif. In addition, comparisons with a 202 amino acid domain residing between epidermal growth factor (EGF) repeats in slit shows this region to be conserved in laminin, agrin and perlecan and, strikingly, also to lie between EGF repeats in both agrin and perlecan. Our analysis suggests this motif is involved in mediating interactions among extracellular proteins. Consistent with our previous characterization of the slit protein, both new motifs are found only in extracellular proteins. The identification of these two conserved motifs in slit reveals that the entire 1469 amino acids of the protein are made up of modular regions similar to those conserved in other extracellular proteins.

Amino Acid Sequence↗
PubMed1992

Description of a modular, low cost, eater meter for the study of feeding behavior and food preferences in fish.

The eater meter described in this paper is especially designed for fish studies. It consists of three parts: the detector, the feeder, and the interface between the detector and the feeder. The detector is a rod that closed a circuit (by contact or through a magnetic detector) when stuck by a fish, the feeder is electric and can be of any commercial model, and the interface is a simple electronic device, or a computer. Some preliminary results obtained with rainbow trout, Oncorhynchus mykiss, are also presented in order to illustrate the uses of this modular eater meter for fish.

Animals↗
PubMed1993

A modularized infrared light matrix system with high resolution for measuring animal behaviors.

The current study provides a new modularized infrared light matrix system (about $200 cost) which is designed to measure the horizontal gross or fine movements, vertical motion, clockwise or anticlockwise turnings, freezing time, and total distance traveled in rats. The system records the sequences of animal's activity in a computer-aided system with a resolution of 0.2 s in time or 1.6 cm in space, and permanently stores all the resulting data in file. The behavioral apparatus was tested for its sensitivity and usability by amphetamine-injected rats. It was found that intraperitoneal administration of amphetamine (1.25-2.50 mg/kg), but not normal saline, produced a dose-related increase in either the horizontal gross or fine movements, vertical motion, clockwise or anticlockwise turnings, or total distance traveled. However, amphetamine injections produced a dose-related decrease in freezing time. Apparently, most of the amphetamine-induced responses obtained by other detecting apparatus can be reproduced easily by the present apparatus. The current detection system possesses the following advantages: a) high resolution, b) high expansion potential, and c) precise and simplified algorithms for behavioral parameter analysis.

Algorithms↗
PubMed1987

Flexible ureteropyeloscopy with modular, "disposable" endoscope.

A flexible modular ureteropyeloscope has been utilized in 36 patients. The flexible tips of this instrument can be replaced and have been available in sizes 6.0F, 8.5F, and 11.0F. The instrument was passed successfully into the ureter in 37 of 38 patients. The most frequent indications were surveillance for fragments after lithotripsy and for diagnosis of radiographic abnormalities in the upper tracts. The high success rate in these patients supports wider application of these techniques and indicates the potential for therapeutic procedures through flexible ureteroscopes.

Disposable Equipment↗
PubMed1990

The segment polarity gene armadillo encodes a functionally modular protein that is the Drosophila homolog of human plakoglobin.

The Drosophila segment polarity gene armadillo is required for pattern formation within embryonic segments and imaginal discs. We have found that armadillo is highly conserved during evolution; it is 63% identical to human plakoglobin, a protein found in adhesive junctions joining epithelial and other cells. We have examined arm protein localization in a number of larval tissues and found that arm protein accumulation within cells shares many features with the accumulation of plakoglobin. We have compared the phenotype and molecular lesions responsible for the different arm mutations. Surprisingly, severely truncated proteins retain some function; the degree of function is strictly correlated with the length of the truncated protein, suggesting that the internally repetitive arm protein is modular in function. We present a possible model for the cellular role of arm.

Alleles↗
PubMed1992

A modular numerical model of the cardiovascular system for studying and training in the field of cardiovascular physiopathology.

A modular numerical model of the cardiovascular system has been developed to reproduce the most important circulatory phenomena in terms of pressure and volume relationships. It is an easy tool to use, designed to be used with a friendly approach on any IBM or compatible personal computer: it offers a wide selection of graphical and numerical outputs and can be rearranged easily for a particular experiment. A set of subroutines related to different circulatory phenomena has been developed; they can be assembled easily together and communicate with each other by two variables. A full description of the existing subroutines is presented in this paper with three different application examples resulting from the rearrangement of the existing software modules: the first concerns the behaviour of the natural ventricle model itself and can be regarded as a ventricle stand-alone characterization test in terms of preload and afterload sensitivities, the second is related to the use of a pneumatic ventricle instead of the model of the natural ventricle, and the third is a full model of the cardiocirculatory system.

Cardiology↗
PubMed1996

Effect of manufacturing tolerances on the micromotion at the Morse taper interface in modular hip implants using the finite element technique.

This study reports on the examination of the effect of manufacturing tolerances on the micromotion at the Morse taper interface in modular hip implants. The finite element technique was used as a tool of analysis. Special emphasis was placed on the consideration of the transient dynamic conditions under which a prosthesis works inside the human body. In order to simulate approximately the repetitive forces acting on a hip implant during the human walking cycle, a time-variant sinusoidal load was applied on the head of the taper. The locking of the Morse taper joint by the surgeon in the operating room at the time of implantation was simulated by specifying an axial displacement to the female taper component as an initial condition.

Biomechanical Phenomena↗
PubMed1993

Characterization of Xenopus laevis complement factor I structure--conservation of modular structure except for an unusual insert not present in human factor I.

Factor I (C3b/C4b inactivator) is a regulatory protein of the classical and alternative complement pathways. In this paper, we report the sequence of Xenopus factor I cDNA and the deduced protein structure. The basic structure of human preprofactor I, NH2-heavy chain-cleavage peptide-light chain-COOH, is conserved in the frog. However, the frog heavy chain contains a highly charged segment of 29 amino acids, encoded by a poly dA-rich mRNA insert, which is not found in human factor I. The modular structure of the frog heavy chain was analyzed, and found to differ vis-à-vis previously published analyses of human factor I. We also evaluate the timing of factor I transcription during frog embryogenesis.

Amino Acid Sequence↗
PubMedDate not supplied

Modular construction of nervous systems: a basic principle of design for invertebrates and vertebrates.

The modular construction of brain tissue is not solely a feature of vertebrate nervous tissue, but is characteristic of many invertebrate nervous systems as well. Modern vertebrate and invertebrate modules vary over several orders of magnitude in volume but vary less in diameter. Although the physiological and anatomical differences between the modules discussed herein are overpowering, their importance to nervous system functions are similar. Modules are the serial and parallel processing units that have allowed large-brained animals to evolve. Many invertebrate modules are discrete, hemispherical lobes, visible on the surface of the brain or nerve cord, whereas most mammalian modules are columnar or ellipsoidal tissue compartments that can only be visualized with specific anatomical methods. Lobes from the largest invertebrates can be more voluminous than any neocortical compartments, but these large lobes are usually not single modules. Large invertebrate lobes contain internal compartments that are single modules and of similar size to their vertebrate analogs. However, vertebrate cortical modules or columns, are far more numerous than the compartments in invertebrate brains and in several cases are known to be adjoined laterally into slabs of tissue that extend for several millimeters. Physiological data support the idea that neural modules are not just anatomical entities, but are active local circuits. The specific activities within each type of module will depend upon its neuronal components, both intrinsic and extrinsic, its functional roles and phylogenetic history. Many cellular and intercellular phenomena common to vertebrates and invertebrates underlie the development of modules. Neuronal and glial interactions and their interplay with the extracellular environment depend upon families of molecules with broad phyletic occurrences. The commonalities of growth mechanisms may to a large degree account for the widespread incidence of neuronal processing units. The strategy of enlarging a nervous system through the replication of the basic units is thought to be advantageous for several reasons. This plan allows nervous systems to economize on the branch sizes and lengths needed for interconnections, to ensure that appropriate targets are reached during development and to modulate specific circuits within a larger network.

Animals↗
PubMed1988

A simple modular tissue bath developed for 'in vitro' studies of the isolated spinal cord.

A tissue bath for studies of the mammalian spinal cord in vitro is described. The modular construction of the bath permits considerable flexibility for accommodating different tissue preparations. The individual components of the bath are easily constructed and the design permits multiple compartment baths to be simply formed. The design principle on which the bath is based may have much wider application than that described.

Animals↗