Pelion Zhuang

• Sun Yat-sen University

Analysis of large biological data sets using a variety of parallel processor computer architectures is a common task in bioinformatics. The efficiency of the analysis can be significantly improved by properly handling redundancy present in these data combined with taking advantage of the unique features of these compute architectures. We describe a...

Structural genomics--large-scale macromolecular 3-dimenional structure determination--is unique in that major participants report scientific progress on a weekly basis. The target database (TargetDB) maintained by the Protein Data Bank (http://targetdb.pdb.org) reports this progress through the status of each protein sequence (target) under conside...

This paper addresses this question

The apoptosis database is a public resource for researchers and students interested in the molecular biology of apoptosis. The resource provides functional annotation, literature references, diagrams/images, and alternative nomenclatures on a set of proteins having 'apoptotic domains'. These are the distinctive domains that are often, if not exclus...

A selection of World Wide Web sites relevant to reviews published in this issue of Current Opinion in Structural Biology.

We are pleased to announce the BioSync Web resource at http://biosync.sdsc.edu. Developed on behalf of the Structural Biology Synchrotron Users Organization (BioSync), this resource serves as a structural biologist's guide to synchrotron facilities. The BioSync organization has collaborated with the San Diego Supercomputer Center to create a compre...

Methanolic extracts of seeds of several (Carex species were found to antagonise the action of 20-hydroxyecdysone in the Drosophila melanogaster microplate-based B(II) cell bioassay. Bioassay-guided HPLC analysis of seeds of Carex pendula (drooping sedge) provided one previously unknown tetrastilbene (cis-miyabenol A) and two known oligostilbenes (k...

Ecdysteroid agonist and antagonist activities can be detected and quantified with the Drosophila melanogaster B(II) cell bioassay. This bioassay is convenient, sensitive and robust. We report the assessment with this bioassay of the activities of a wide range of compounds representing a number of classes of natural products. Many compounds were ina...

An all-against-all protein structure comparison using the Combinatorial Extension (CE) algorithm applied to a representative set of PDB structures revealed a gallery of common substructures in proteins (http://cl.sdsc.edu/ce.html). These substructures represent commonly identified folds, domains, or components thereof. Most of the subsequences form...

During the determination of macromolecular structures, scientists routinely use complex graphics software to display various representations of the molecule of interest. Once the structure determination is complete, coordinates are deposited in the Protein Data Bank (PDB), from where anyone with an Internet connection may download and view them or...

We have developed a new algorithm for the alignment of multiple protein structures based on a Monte Carlo optimization technique. The algorithm uses pair-wise structural alignments as a starting point. Four different types of moves were designed to generate random changes in the alignment. A distance-based score is calculated for each trial move an...

The database reported here is derived using the Combinatorial Extension (CE) algorithm which compares pairs of protein polypeptide chains and provides a list of structurally similar proteins along with their structure alignments. Using CE, structure–structure alignments can provide insights into biological function. When a protein of known function...

The Conserved Key Amino Acid Positions DataBase (CKAAPs DB) provides access to an analysis of structurally similar proteins with dissimilar sequences where key residues within a common fold are identified. The derivation and significance of CKAAPs starting from pairwise structure alignments is described fully in Reddy et al. [Reddy,B.V.B., Li,W.W.,...

The PDB has created systems for the processing, exchange, query, and distribution of data that will enable many aspects of high throughput structural genomics.

Crystallographers were motivated 10 years ago to develop a simple and consistent data representation for the exchange and archiving of data associated with the crystallographic experiment and the final structure. As this process evolved (and the data grew at near exponential rates) came the recognition that this representation should also facilitat...

Comparing and subsequently classifying protein structures information has received significant attention concurrent with the increase in the number of experimentally derived 3-dimensional structures. Classification schemes have focused on biological function found within protein domains and on structure classification based on topology. Here an alt...

A novel bacterial esterase that cleaves esters on halogenated cyclic compounds has been isolated from an Alcaligenes species. This esterase 713 is encoded by a 1062 base pair gene. The presence of a leader sequence of 27 amino acids suggests that this enzyme is exported from the cytosol. Esterase 713 has been over-expressed in Agrobacterium without...

Comparisons of protein sequence via cyclic training of Hidden Markov Models (HMMs) in conjunction with alignments of three-dimensional structure, using the Combinatorial Extension (CE) algorithm, reveal two putative EF-hand metal binding domains in acetylcholinesterase. Based on sequence similarity, putative EF-hands are also predicted for the neur...

The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules. This paper describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information, and near-term plans for the future development of the resource.

Motivation: Biological databases, with their rapidly expanding contents, are indispensable tools in the quest to understand more about biological function. However, a serious user of a database that comprises a large collection of data, collected over a long period, will likely be struck by the inconsistency in reporting individual items of data....

The crystallographic problem: For a crystallographer, the visualization of a protein structure is a commonplace, almost trivial task, performed routinely throughout the structure determination process. For the more general audience, however, obtaining a useful visual representation of a model can be considerably more challenging, perhaps requiring...

The enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the archaea shows low sequence identity (16-20%) with its eubacterial and eukaryotic counterparts. The crystal structure of the apo GAPDH from Sulfolobus solfataricus has been determined by multiple isomorphous replacement at 2.05 A resolution. The enzyme has several differences in se...

Guidelines for submitting commentsPolicy: Comments that contribute to the discussion of the article will be posted within approximately three business days. We do not accept anonymous comments. Please include your email address; the address will not be displayed in the posted comment. Cell Press Editors will screen the comments to ensure that they...

The Protein Data Bank (PDB) is a large and rapidly growing standard repository of complex biological macromolecules. Existing software tools for the PDB, including storage management, are quite inflexible and work in isolation. We are using object-oriented design and object-oriented database techniques in the construction of a toolbox for the PDB....

A novel bacterial esterase has been crystallized in two forms suitable for X-ray diffraction studies. Crystals have been obtained by vapour-phase diffusion at 290 K using ammonium sulfate as precipitant. The first crystals grew in space group C2 with unit-cell parameters a = 134.7, b = 55.8, c = 110.3 A, beta = 125.1 degrees. A monoclinic data set...

Computer-based multimedia technology for distance learning and research has come of age--the price point is acceptable, domain experts using off-the-shelf software can prepare compelling materials, and the material can be efficiently delivered via the Internet to a large audience. While not presenting any new scientific results, this paper outlines...

A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Structural Biology.

Databases containing macromolecular structure data provide a crystallographer with important tools for use in solving, refining and understanding the functional significance of their protein structures. Given this importance, this paper briefly summarizes past progress by outlining the features of the significant number of relevant databases develo...

A selection of World Wide Web sites relevant to reviews published in this issue of Current Opinion in Structural Biology.

A new algorithm is reported which builds an alignment between two protein structures. The algorithm involves a combinatorial extension (CE) of an alignment path defined by aligned fragment pairs (AFPs) rather than the more conventional techniques using dynamic programming and Monte Carlo optimization. AFPs, as the name suggests, are pairs of fragme...

A selection of World Wide Web sites relevant to reviews published in this issue of Current Opinion in Structural Biology.

Guidelines for submitting commentsPolicy: Comments that contribute to the discussion of the article will be posted within approximately three business days. We do not accept anonymous comments. Please include your email address; the address will not be displayed in the posted comment. Cell Press Editors will screen the comments to ensure that they...

Motivation: To provide data management tools to maintain and query efficiently experimental and derived protein data with the goal of providing new insights into structure-function relationships. The tools should be portable, extensible, and accessible locally, or via the World Wide Web, providing data that would not otherwise be available. Resul...

The goal of this paper is to give an overview of the performances of InGaP HBTs for X-band power applications. A reminder of the peculiarities concerning this device, compared to the more conventional GaAlAs/GaAs HBT, is given as an introduction. A presentation of some recent Thomson-CSF X-band power results are presented and compared to the litera...

WPDB version 2.0 is a Microsoft-Windows-based program for browsing and interrogating native and derived structural features of biological macromolecules using data obtained from the Protein Data Bank (PDB). Major features of WPDB are a 20-fold compression of PDB files and query and analysis tools. The latter permit the geometric and sequence proper...

First, a review of the laboratories, which have studied the GaInP/GaAs HBT for electronic applications, is given. Then the peculiarities of this device are addressed compared to the more conventional GaAlAs/GaAs HBTs. Finally, a presentation of some recent Thomson-CSF X-band power results are presented and compared to the literature

PDBtool version 1.0 is an interactive Unix and X/Motif based computer program for investigating the 3-dimensional (3-D) structure of proteins using data represented by the Protein Data Bank (PDB) format. Major components of PDBtool include a 3-D structure viewer, text browsers from which to investigate components of the structure under study, and a...

The broad goal of the work has been to design, implement, and begin to use an extensible object oriented framework which represents biological macromolecules and which can be queried in efforts to better understand the biological significance of these complex molecules. Using this framework a variety of methods can be added (by us and others) with...

PDBlib is an extensible object-oriented class library written in C++ for representing the three-dimensional structure of biological macromolecules. The software design strategy, features of many of the 129 classes currently distributed with the library, and two sample applications which use the library are described. Version 1.0 of the library repr...

Macromolecular query language (MMQL) is an extensible interpretive language in which to pose questions concerning the experimental or derived features of the 3-D structure of biological macromolecules. MMQL portends to be intuitive with a simple syntax, so that from a user's perspective complex queries are easily written. A number of basic queries...

GaInP/GaAs HBT technology is an excellent alternative to GaAlAs/GaAs HBTs. We present new X-Band power results both on discrete devices and on MMICs obtained using this new type of HBT. 12-2×30-¿m2 finger discrete devices show an output power of 1W at 10 GHz with a power added efficiency of 43% under near class A bias conditions. The dependence o...

An algorithm is described for mapping DNA contigs based on an interval graph (IG) representation. In general terms, the input to the algorithm is a set of binary overlapping relations among finite intervals spread along a real line, from which the algorithm generates sets of ordered overlapping fragments spanning that line. The implications of a mo...

A family of fully monolithic VCOs utilizing GaInP/GaAs HBTs are presented for the first time. They operate at 14 GHz and 28 GHz with tuning bandwidths ranging from 10.7% to 19.6%. Output powers vary between -9dBm and +3 dBm with an integrated 6 dB attenuator to reduce pulling. The fabrication yield is higher than 50%. On-wafer measurements show a v...

A family of fully monolithic VCOs utilizing GaInP/GaAs HBTs are presented for the first time. They operate at 14 GHz and 28 GHz with tuning bandwidths ranging from 10.7% to 19.6%. Output powers vary between -9 dBm and +3 dBm with an integrated 6 dB attenuator to reduce pulling. The fabrication yield is higher than 50%. On-wafer measurements show a...

The technology and performances of microwave GaInP/GaAs Heterojunction Bipolar Transistors (HBT) developed at the THOMSON-CSF Central Research Laboratory (LCR), are presented. HBTs are very promising devices for their high power capability (3 W/mm) and suitable to class B operation. Those features are very attractive to produce high efficiency X-ba...

PDBlib is an extensible object oriented class library written in C++ for representing the 3-dimensional structure of biological macromolecules. PDBlib forms the kernel of a larger software framework being developed for assiting in knowledge discovery from macromolecular structure data. The software design strategy used by PDBlib, how the library ma...

Mouse monoclonal antibodies have been raised to the C-terminal region of rat type II voltage-dependent sodium channel. One of these, designated 13A4-G4, recognizes a 260 Kd putative sodium channel protein in human fetal brain, heart and skeletal muscle, at 14-18 weeks of gestation. Faint immunoreactivity is also present in human fetal kidney but no...

The CPU time required to complete a cycle of restrained least-squares refinement of a protein structure from X-ray crystallographic data using the FORTRAN codes PROTIN and PROLSQ are reported for 48 different processors, ranging from single-user workstations to supercomputers. Sequential, vector, VLIW, multiprocessor, and RISC hardware architecture...

Six patients with neoplastic melanomatous meningitis were studied. The diagnosis of this complication of malignant disease rests on the demonstration of malignant cells within the CSF. The addition of monoclonal antibody immunocytology to conventional techniques significantly improved the diagnostic sensitivity of CSF cytology, allowing for earlier...

A pilot study was performed to investigate the toxicity and therapeutic effect of radiolabeled antibody administered intrathecally in patients with leptomeningeal tumors. Five patients who failed conventional therapy received between 11 mCi and 40 mCi of radiolabeled antibody. The choice of antibody varied depending on the immunophenotype of the tu...

Six cases of primary cerebral lymphoma were immunophenotyped and analysed by Southern blotting to determine the clonality and lineage of these neoplasms. Molecular analysis showed that they were of B cell origin, and the rearrangement of both heavy and light chain immunoglobulins in malignant cells showed that they were monoclonal populations of ma...

The antigenic characteristics of 20 primary cerebral lymphomas have been defined by their reactivity with a panel of monoclonal antibodies recognizing differentiation antigens of lymphocytes and other cell types. In 7 out of 20 cases (35%), immunohistological results were diagnostically crucial and this approach appeared almost to double the detect...

A monoclonal antibody (UJ181.4) was labelled with 131I and given intrathecally to a patient who was critically ill with neoplastic meningitis due to a disseminated pineoblastoma. The target antigen had first been demonstrated on tumour cells by immunocytological testing of cerebrospinal fluid (CSF). As a preparation for therapy, a test dose of 131I...

A number of relatively low-cost processors are now available which employ architectural features previously found only on very expensive supercomputers. The speed of these computers makes it possible to reduce the time to solution of certain problems and to resolve large problems that previously were too time consuming to perform locally. A brief o...

A panel of monoclonal antibodies including antibodies against neuroectodermal antigens, (UJ13A, UJ127.11, UJ181.4), leukocytes (2D1), intermediate filament antigens cytokeratin (LE61), Vimentin, Desmin (Labsystems, Helsinki, Finland), myoglobin, and neurofilament (155) antigens were assessed for their use as an adjunct to light microscopy in pediat...

Over recent years we have been studying the possibility of targeting radiolabelled monoclonal antibodies to human brain tumours in vivo. This work began with the development of panels of monoclonal antibodies for use in the diagnosis of brain tumour biopsies and cerebrospinal fluid infiltrates (1). Certain of these antibodies were then chosen for u...

The BJC is owned by Cancer Research UK, a charity dedicated to understanding the causes, prevention and treatment of cancer and to making sure that the best new treatments reach patients in the clinic as quickly as possible. The journal reflects these aims. It was founded more than fifty years ago and, from the start, its far-sighted mission was to...

Monoclonal antibody UJ13A, radiolabelled with 131I, was intravenously administered to patients with primary brain tumours. The antigen recognised by UJ13A is present on most neuroectodermally derived tissue. The ratio of uptake in tumour to normal brain, assessed by scintigraphy, improved with time. Maximal tumour uptake occurred between 4 and 48 h...

Following appropriate animal experiments, radioimmunolocalisation of primary cerebral tumours in 5 patients was performed with a 131I-labelled mouse monoclonal antibody which recognises an antigen expressed by most normal and malignant neuroectodermal tissues. Images were taken at 10 minutes, 4 hours, 24 hours, and thence daily, from the time of in...

Arterial pressure and flow measurements can be analysed using a mathematical model of the circulation. A comparison of four models of the circulation used in this way is presented. The results indicate some criteria for evaluating circulation model performance in general.

Several models of the circulation have been developed in physiological research. Such models can be matched to patient measurements and then used as a clinical diagnostic tool. We have examined methods for matching digital computer models and evaluated the efficiency of some of them. We present two methods which we have developed and found useful.

A cardiac monitoring system has been developed that incorporated phasic aortic blood flow measurement by an extractable electromagnetic flow probe and high-fidelity arterial blood pressure recordings. Cardiac output, stroke volume, and peak aortic blood flow are measured continuously; using logarithmic amplifiers, the pressure-flow derivatives of l...

Continuous measurements on patients after cardiac surgery are usually limited to blood pressure and ECG. This article describes a new monitor which combines instantaneous arotic flow and arterial pressure measurements to derive stroke volume, ventricular power, stroke work, and an indication of left ventricular afterload. The methods used to obtain...

Without Abstract

Established methods for the assay of aminoglycoside antibiotics in serum are imperfect for routine use in that either they are slow to yield results or they are time consuming in terms of laboratory labour. A recently introduced method which depends on inhibition of bacterial urease activity by the antibiotic goes some way towards overcoming these...

Thesis (B.S.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 1892.

Thesis (Ph. D.)--University of London, 1980.