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Biomedical subjects

P L Miller

Publications and source records attributed to P L Miller.

At least 19 recordsLinked to original sources
PubMed1992

Molecular dynamics simulation on a network of workstations using a machine-independent parallel programming language.

Molecular dynamics simulations investigate local and global motion in molecules. Several parallel computing approaches have been taken to attack the most computationally expensive phase of molecular simulations, the evaluation of long range interactions. This paper reviews these approaches and develops a straightforward but effective algorithm using the machine-independent parallel programming language, Linda. The algorithm was run both on a shared memory parallel computer and on a network of high performance Unix workstations. Performance benchmarks were performed on both systems using two proteins. This algorithm offers a portable cost-effective alternative for molecular dynamics simulations. In view of the increasing numbers of networked workstations, this approach could help make molecular dynamics simulations more easily accessible to the research community.

Algorithms↗
PubMed1992

Harnessing networked workstations as a powerful parallel computer: a general paradigm illustrated using three programs for genetic linkage analysis.

It is widely accepted that parallel computers, which have the ability to execute different parts of a program simultaneously, will offer dramatic speed-up for many time-consuming biological computations. The paper describes how the use of the machine-independent parallel programming language, Linda, allows parallel programs to run on an institution's network of workstations. In this way, an institution can harness existing hardware, which is often either idle or vastly underutilized, as a powerful 'parallel machine' with supercomputing capability. The paper illustrates this very general paradigm by describing the use of Linda to parallelize three widely used programs for genetic linkage analysis, a mathematical technique used in gene mapping. The paper then discusses a number of technical, administrative and social issues that arise when creating such a computational resource.

Algorithms↗
PubMed1992

Comparing machine-independent versus machine-specific parallelization of a software platform for biological sequence comparison.

A platform program that performs biological sequence comparison provides a case study to compare the relative advantages of a machine-independent approach to parallel computation versus a machine-specific approach. The program consists of two routines: (i) PSCANLIB, which compares a single biological sequence against a database of sequences, and (ii) PCOMPLIB, which compares a database of sequences against another database of sequences, or against itself. The program was first parallelized to run on the Intel Hypercube parallel computer using native Hypercube commands to coordinate the parallel computation. The parallelization logic of the program was then translated into a machine-independent parallel programming language, Linda. These two approaches to parallelization are contrasted in terms of: (i) the expressive power of the logic that coordinates the parallel computation, (ii) the portability of the machine-independent version to other parallel machines and (iii) the relative efficiency of the two versions of the program. In the benchmark tests reported, the benefits of the machine-independent approach were achieved with only a modest sacrifice in efficiency.

Algorithms↗
PubMed1992

Fast computation of genetic likelihoods on human pedigree data.

Gene mapping and genetic epidemiology require large-scale computation of likelihoods based on human pedigree data. Although computation of such likelihoods has become increasingly sophisticated, fast calculations are still impeded by complex pedigree structures, by models with many underlying loci and by missing observations on key family members. The current paper 'introduces' a new method of array factorization that substantially accelerates linkage calculations with large numbers of markers. This method is not limited to nuclear families or to families with complete phenotyping. Vectorization and parallelization are two general-purpose hardware techniques for accelerating computations. These techniques can assist in the rapid calculation of genetic likelihoods. We describe our experience using both of these methods with the existing program MENDEL. A vectorized version of MENDEL was run on an IBM 3090 supercomputer. A parallelized version of MENDEL was run on parallel machines of different architectures and on a network of workstations. Applying these revised versions of MENDEL to two challenging linkage problems yields substantial improvements in computational speed.

Algorithms↗
PubMed1992

Prototyping an institutional IAIMS/UMLS information environment for an academic medical center.

The paper describes a prototype information environment designed to link network-based information resources in an integrated fashion and thus enhance the information capabilities of an academic medical center. The prototype was implemented on a single Macintosh computer to permit exploration of the overall "information architecture" and to demonstrate the various desired capabilities prior to full-scale network-based implementation. At the heart of the prototype are two components: a diverse set of information resources available over an institutional computer network and an information sources map designed to assist users in finding and accessing information resources relevant to their needs. The paper describes these and other components of the prototype and presents a scenario illustrating its use. The prototype illustrates the link between the goals of two National Library of Medicine initiatives, the Integrated Academic Information Management System (IAIMS) and the Unified Medical Language System (UMLS).

Academic Medical Centers↗
PubMed1992

Online bibliographic information: integration into an emerging IAIMS environment.

The Medical Library at Yale University has developed an online free-text database containing Current Contents citations. The database was designed to be integrated into an emerging campus-wide information environment. To this end Current Contents at Yale was designed with a user interface familiar to the Yale community, an alerting service based on electronic mail, and search expansion using the National Library of Medicine's Meta-1 metathesaurus.

Consumer Behavior↗
PubMed1992

Automated online transition from the medical record to the psychiatric literature.

Psych Topix is a knowledge-based program which guides the clinician from an on-line clinical report to a search of the psychiatric literature or of other relevant databases. It provides this guidance by using an outline of key topics in a clinical field to provide "concept-based" links. Each topic is augmented with an activation expression to signal when that topic is potentially relevant to a case, and with database search expressions to allow focused retrieval of information. The bibliographic retrieval component of Psych Topix is currently operational as part of the daily, routine operation of a psychiatric consultation service. The system is also implemented in a demonstration mode to provide retrieval from three additional textual databases. The current Psych Topix system provides a working demonstration of the clinical feasibility of using concept-based links to facilitate the focused, automated transition between on-line medical databases.

Expert Systems↗
PubMed1992

Automated integration of external databases: a knowledge-based approach to enhancing rule-based expert systems.

Expert system applications in the biomedical domain have long been hampered by the difficulty inherent in maintaining and extending large knowledge bases. We have developed a knowledge-based method for automatically augmenting such knowledge bases. The method consists of automatically integrating data contained in commercially available, external, on-line databases with data contained in an expert system's knowledge base. We have built a prototype system, named DBX, using this technique to augment an expert system's knowledge base as a decision support aid and as a bibliographic retrieval tool. In this paper, we describe this prototype system in detail, illustrate its use and discuss the lessons we have learned in its implementation.

Asthma↗
PubMed1992

PFGE MAPPER and PFGE READER: two tools to aid in the analysis and data input of pulse field gel electrophoresis maps.

Pulse field gel electrophoresis mapping is an important technique for characterizing large segments of DNA. We have developed two tools to aid in the construction of pulse field electrophoresis gel maps: PFGE READER which stores experimental conditions and calculates fragment sizes and PFGE MAPPER which constructs pulse field gel electrophoresis maps.

Clinical Laboratory Information Systems↗
PubMed1992

CHROMINFO: a database for viewing and editing top-level chromosome data.

CHROMINFO is a prototype database that is intended to serve as a liaison tool for researchers working in different centers on mapping of the same mammalian chromosome. It provides a bird's-eye-view of top-level entities on a chromosome (such as gene loci, chromosome breakpoints and contigs) and relates them to one another in one dimension, the axis of the chromosome. Consensus data can be entered, edited, queried and displayed in a variety of ways. Summary evidence for consensus data can also be stored and retrieved. Information may be downloaded from the Genome Data Base periodically, and order and distance information is then incorporated. The prototype of CHROMINFO was built for human chromosome 16. Versions have been created for several other chromosomes.

Alleles↗
PubMed1991

A parallel computing approach to genetic sequence comparison: the master-worker paradigm with interworker communication.

We have implemented a parallel version of a dynamic programming biological sequence comparison algorithm to study the potential applicability of using parallel computers for genetic sequence comparisons. Our parallel program is built using C-Linda, a machine-independent parallel programming language, and was tested on both a 10 CPU Sequent Symmetry and a 64 CPU Intel Hypercube. C-Linda implements a shared associative memory model, "tuple space," through which multiple processes can communicate and coordinate control. In our master-worker (MW) parallel implementation, a master process creates several worker processes, extracts a test sequence and multiple library sequences from a database and stores them in tuple space. Each worker reads the test sequence and then repeatedly extracts library strings from tuple space, performs pairwise sequence comparison using a local comparison algorithm to generate a similarity score, and returns the similarity scores to tuple space. The master collects the scores from tuple space and identifies the best match over all library sequences. We also implemented a method of global interworker communication to reduce the total search time by stopping those string comparisons that had no chance of improving on the current best match. Comparisons of the total run time, speedup, and efficiency were made for parallel and sequential versions of a basic MW implementation as well as versions with the global abort threshold.

Algorithms↗
PubMed1991

Parallelizing genetic linkage analysis: a case study for applying parallel computation in molecular biology.

Parallel computers offer a solution to improve the lengthy computation time of many conventional, sequential programs used in molecular biology. On a parallel computer, different pieces of the computation are performed simultaneously on different processors. LINKMAP is a sequential program widely used by scientists to perform genetic linkage analysis. We have converted LINKMAP to run on a parallel computer, using the machine-independent parallel programming language, Linda. Using the parallelization of LINKMAP as a case study, the paper outlines an approach to converting existing highly iterative programs to a parallel form. The paper describes the steps involved in converting the sequential program to a parallel program. It presents performance benchmarks comparing the sequential version of LINKMAP with the parallel version running on different parallel machines. The paper also discusses alternative approaches to the problem of "load balancing," making sure the computational load is shared as evenly as possible among the available processors.

Chromosome Mapping↗
PubMed1991

Parallel computation and FASTA: confronting the problem of parallel database search for a fast sequence comparison algorithm.

We have parallelized the FASTA algorithm for biological sequence comparison using Linda, a machine-independent parallel programming language. The resulting parallel program runs on a variety of different parallel machines. A straight-forward parallelization strategy works well if the amount of computation to be done is relatively large. When the amount of computation is reduced, however, disk I/O becomes a bottleneck which may prevent additional speed-up as the number of processors is increased. The paper describes the parallelization of FASTA, and uses FASTA to illustrate the I/O bottleneck problem that may arise when performing parallel database search with a fast sequence comparison algorithm. The paper also describes several program design strategies that can help with this problem. The paper discusses how this bottleneck is an example of a general problem that may occur when parallelizing, or otherwise speeding up, a time-consuming computation.

Algorithms↗
PubMed1991

SENEX: a computer-based representation of cellular signal transduction processes in the central nervous system.

The SENEX project is exploring knowledge representation in the neurobiology of ageing through object-oriented programming. SENEX is built from a classification structure of biologic entities and significant relationships among them. For example, an enzyme is an entity and an enzymatic reaction is a relationship among enzyme, cofactor(s), substrate(s) and product(s). There are currently 2600 classes of entities and 50 classes of relationships in SENEX. The class structure serves several functions. One function is to interrelate general and specific categories of molecular and morphologic entities. For example, tyrosine kinase and serine/threonine kinase are specific types of the more general class of protein kinase enzymes. Another function of the class structure is to serve as a network through which inheritance of attributes may occur. For example, the attribute 'subunits' is inherited by all subclasses of the general class multisubunit protein. Information may be accessed through links established in the class structure and through links relating one object as part of another. Relationships form the basis of separate modules within SENEX. This paper describes the types of relationships currently used and planned in the representation of age-related changes in cellular signal transduction processes of mammalian central nervous systems. We also describe tools for specific retrieval of relationships and for tracing links in complex reaction cascades. Application of these tools to identifying possible signal transduction pathways to guide further exploration through experimentation is discussed.

Aging↗
PubMed1991

Glomerular hypertrophy accelerates hypertensive glomerular injury in rats.

Micropuncture and morphological studies were performed in four groups of rats that received subcutaneous infusions of saline or angiotensin II (ANG II) for 8 wk. Group 1 rats received saline; group 2 rats were subjected to uninephrectomy and then received saline; group 3 rats received ANG II (100 ng/min); and group 4 rats were subjected to uninephrectomy and then received ANG II (50 ng/min). In comparison with group 1 rats, group 2 rats exhibited no increase in mean arterial pressure (MAP) (group 2, 102 +/- 6 mmHg; group 1, 104 +/- 10 mmHg) or glomerular capillary pressure (PGC) (group 2, 56 +/- 3 mmHg; group 1, 55 +/- 4 mmHg). In the absence of glomerular hypertension, an increase in glomerular volume (VG) was not associated with glomerular sclerosis in group 2 rats. In contrast to group 2 rats, group 3 rats exhibited increases in MAP (161 +/- 13 mmHg) and PGC (70 +/- 7 mmHg) without any increase in VG. Glomerular hypertension was associated with development of increased albuminuria and glomerular sclerosis in group 3. Group 4 rats exhibited increases in MAP (157 +/- 18 mmHg), PGC (69 +/- 6 mmHg), and VG. These rats also developed glomerular sclerosis and significantly more albuminuria than would have been expected from simple combination of effects of uninephrectomy and ANG II infusion. Additional morphological studies were performed in two groups of rats that received ANG II for 12 wk. Over this period, uninephrectomized group 6 rats infused with ANG II (50 ng/min) developed markedly greater albuminuria and glomerular sclerosis than intact group 5 rats infused with ANG II (100 ng/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1991

Parallel computation for biological sequence comparison: comparing a portable model to the native model for the Intel Hypercube.

A parallel program for inter-database sequence comparison was developed on the Intel Hypercube using two models of parallel programming. One version was built using machine-specific Hypercube parallel programming commands. The other version was built using Linda, a machine-independent parallel programming language. The two versions of the program provide a case study comparing these two approaches to parallelization in an important biological application area. Benchmark tests with both programs gave comparable results with a small number of processors. As the number of processors was increased, the Linda version was somewhat less efficient. The Linda version was also run without change on Network Linda, a virtual parallel machine running on a network of desktop workstations.

Algorithms↗