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W Miller

Publications and source records attributed to W Miller.

At least 163 records · Page 9Linked to original sources
PubMed1992

Parallelization of a local similarity algorithm.

The local similarity problem is to determine the similar regions within two given sequences. We recently developed a dynamic programming algorithm for the local similarity problem that requires only space proportional to the sum of the two sequence lengths, whereas earlier methods use space proportional to the product of the lengths. In this paper, we describe how to parallelize the new algorithm and present results of experimental studies on an Intel hypercube. The parallel method provides rapid, high-resolution alignments for users of our software toolkit for pairwise sequence comparison, as illustrated here by a comparison of the chloroplast genomes of tobacco and liverwort.

Algorithms↗
PubMed1992

Aligning two sequences within a specified diagonal band.

We describe an algorithm for aligning two sequences within a diagonal band that requires only O(NW) computation time and O(N) space, where N is the length of the shorter of the two sequences and W is the width of the band. The basic algorithm can be used to calculate either local or global alignment scores. Local alignments are produced by finding the beginning and end of a best local alignment in the band, and then applying the global alignment algorithm between those points. This algorithm has been incorporated into the FASTA program package, where it has decreased the amount of memory required to calculate local alignments from O(NW) to O(N) and decreased the time required to calculate optimized scores for every sequence in a protein sequence database by 40%. On computers with limited memory, such as the IBM-PC, this improvement both allows longer sequences to be aligned and allows optimization within wider bands, which can include longer gaps.

Algorithms↗
PubMed1992

Immunogenicity of conjugate vaccines consisting of pneumococcal capsular polysaccharide types 6B, 14, 19F, and 23F and a meningococcal outer membrane protein complex.

In an effort to prepare pneumococcal (Pn) capsular polysaccharide (Ps) vaccines that would be immunogenic in infants, covalent conjugates were prepared for Pn types 6B, 14, 19F, and 23F. Each Ps type was covalently bound to an outer membrane protein complex from Neisseria meningitidis serogroup B and evaluated for immunogenicity in mice and infant monkeys. The conjugates induced specific anti-Ps antibody responses in mice and in infant rhesus and African green monkeys; a conjugate of 6B and outer membrane protein complex was immunogenic at Ps doses as low as 20 ng. Although low levels of the Pn group-common cell wall polysaccharide were present in all type-specific Ps preparations, anti-cell wall polysaccharide responses induced by covalent conjugates were < 1% of the total anti-Ps response after two doses of vaccine. In contrast, the anti-cell wall polysaccharide response of a noncovalent conjugate represented 41% of the anti-Ps response after two doses. Relative T-cell dependence, a requirement for the human target population of infants less than 18 months old, was demonstrated for all four Pn Ps conjugates in an athymic mouse model. Therefore, these Pn Ps-outer membrane protein complex conjugate vaccines are excellent candidates for evaluation in human infants.

Animals↗
PubMed1992

Analysis of conserved domains and sequence motifs in cellular regulatory proteins and locus control regions using new software tools for multiple alignment and visualization.

With the tremendous expansion of molecular sequence data in recent years, multiple alignment is arguably one of the two most important analytic techniques (the other being fast database searching). A number of useful approaches to this problem have previously been developed, but often they are limited to only a subset of multiple-alignment applications and cannot easily deal with the complex structural organization seen in an increasing number of sequences. For example, a single sequence may contain several domains of different evolutionary origins, and the multiplicities and relative ordering of these domains may be quite different among related sequences. Here we describe an integrated set of interactive Unix tools that combines several multiple-alignment techniques with traditional "dot-plot" visualization to provide a flexible environment for approaching complex sequence analysis problems. We apply these tools to the identification and characterization of "catalytic" domains in ras and rho/rac GTPase-activating proteins, to "Src homology" (SH2, SH3) domains in cytoplasmic signaling proteins, to repetitive sequence motifs in the alpha and beta subunits of protein prenyltransferases, and to regulatory DNA sequences in the locus control region of the beta-globin gene cluster.

Alkyl and Aryl Transferases↗
PubMed1991

Sequence and comparative analysis of the rabbit alpha-like globin gene cluster reveals a rapid mode of evolution in a G + C-rich region of mammalian genomes.

A sequence of 10,621 base-pairs from the alpha-like globin gene cluster of rabbit has been determined. It includes the sequence of gene zeta 1 (a pseudogene for the rabbit embryonic zeta-globin), the functional rabbit alpha-globin gene, and the theta 1 pseudogene, along with the sequences of eight C repeats (short interspersed repeats in rabbit) and a J sequence implicated in recombination. The region is quite G + C-rich (62%) and contains two CpG islands. As expected for a very G + C-rich region, it has an abundance of open reading frames, but few of the long open reading frames are associated with the coding regions of genes. Alignments between the sequences of the rabbit and human alpha-like globin gene clusters reveal matches primarily in the immediate vicinity of genes and CpG islands, while the intergenic regions of these gene clusters have many fewer matches than are seen between the beta-like globin gene clusters of these two species. Furthermore, the non-coding sequences in this portion of the rabbit alpha-like globin gene cluster are shorter than in human, indicating a strong tendency either for sequence contraction in the rabbit gene cluster or for expansion in the human gene cluster. Thus, the intergenic regions of the alpha-like globin gene clusters have evolved in a relatively fast mode since the mammalian radiation, but not exclusively by nucleotide substitution. Despite this rapid mode of evolution, some strong matches are found 5' to the start sites of the human and rabbit alpha genes, perhaps indicating conservation of a regulatory element. The rabbit J sequence is over 1000 base-pairs long; it contains a C repeat at its 5' end and an internal region of homology to the 3'-untranslated region of the alpha-globin gene. Part of the rabbit J sequence matches with sequences within the X homology block in human. Both of these regions have been implicated as hot-spots for recombination, hence the matching sequences are good candidates for such a function. All the interspersed repeats within both gene clusters are retroposon SINEs that appear to have inserted independently in the rabbit and human lineages.

Animals↗
PubMed1991

Software tools for analyzing pairwise alignments of long sequences.

Pairwise comparison of long stretches of genomic DNA sequence can identify regions conserved across species, which often indicate functional significance. However, the novel insights frequently must be windowed from a flood of information; for instance, running an alignment program on two 50-kilobase sequences might yield over a hundred pages of alignments. Direct inspection of such a volume of printed output is infeasible, or at best highly undesirable, and computer tools are needed to summarize the information, to assist in its analysis, and to report the findings. This paper describes two such software tools. One tool prepares publication-quality pictorial representations of alignments, while another facilitates interactive browsing of pairwise alignment data. Their effectiveness is illustrated by comparing the beta-like globin gene clusters between humans and rabbits. A second example compares the chloroplast genomes of tobacco and liverwort.

Animals↗
PubMed1991

Mapping sequenced E.coli genes by computer: software, strategies and examples.

Methods are presented for organizing and integrating DNA sequence data, restriction maps, and genetic maps for the same organism but from a variety of sources (databases, publications, personal communications). Proper software tools are essential for successful organization of such diverse data into an ordered, cohesive body of information, and a suite of novel software to support this endeavor is described. Though these tools automate much of the task, a variety of strategies is needed to cope with recalcitrant cases. We describe such strategies and illustrate their application with numerous examples. These strategies have allowed us to order, analyze, and display over one megabase of E. coli DNA sequence information. The integration task often exposes inconsistencies in the available data, perhaps caused by strain polymorphisms or human oversight, necessitating the application of sound biological judgment. The examples illustrate both the level of expertise required of the database curator and the knowledge gained as apparent inconsistencies are resolved. The software and mapping methods are applicable to the study of any genome for which a high resolution restriction map is available. They were developed to support a weakly coordinated sequencing effort involving many laboratories, but would also be useful for highly orchestrated sequencing projects.

Base Sequence↗
PubMed1991

Absent neutrophil alkaline phosphatase in the eosinophilia myalgia syndrome associated with L-tryptophan use.

The clinical constellation of leukocytosis, thrombocytosis, and low or absent stainable neutrophil alkaline phosphatase (NAP) is considered characteristic of chronic myelogenous leukemia (CML). CML with eosinophilic differentiation (eosinophilic leukemia) is well described, and leukemia and other clonal hematologic malignancies are associated with the syndrome of eosinophilic fasciitis. We describe leukocytosis, thrombocytosis, eosinophilia, mild basophilia, and absent stainable NAP, initially suggesting the diagnosis of CML in a patient with the eosinophilia myalgia syndrome associated with L-tryptophan use, a condition resembling eosinophilic fasciitis. Cytogenetic and molecular genetic studies failed to demonstrate a clonal proliferation of eosinophils.

Adult↗
PubMed1991

Comparative safety and immunogenicity of yeast recombinant hepatitis B vaccines containing S and pre-S2 + S antigens.

One hundred and four healthy, hepatitis B virus (HBV) seronegative males were enrolled in a single blind, randomized pilot study to compare antibody and clinical responses to a yeast recombinant pre-S2 + S vaccine and a yeast recombinant S antigen vaccine (Recombivax HBR). Participants received either a 12, 24 or 48 micrograms dose of pre-S2 + S vaccine (with a 1:5 ratio by weight of pre-S2 and S antigens) or a 10 micrograms dose of Recombivax HBR by intramuscular injection at 0, 1 and 6 months; their serological and biochemical responses were measured at 0, 1, 2, 3, 6 and 7 months, while their clinical responses were monitored for 5 days after each injection. The proportion of vaccines with minor local or systemic complaints (mainly sore arm, malaise, myalgia, fatigue) and the proportion developing antibody to surface antigen (anti-HBs) were similar for all vaccine groups. Transient elevations in alanine aminotransferase occurred infrequently. By 7 months almost all vaccinees developed anti-HBs, but titres were generally higher among recipients of pre-S2 + S vaccine. Antibody to pre-S2 antigen developed in 70-75% by 2 months and in 91-96% by 7 months. These data imply that the recombinant yeast pre-S2 + S vaccine is as well tolerated and as immunogenic as Recombivax HBR. Further studies are being conducted to assess antibody responses in larger numbers of healthy adults as well as in special populations with sub-optimal responses to currently licensed hepatitis B vaccines.

Adult↗
PubMed1991

Improved algorithms for searching restriction maps.

We present algorithms for searching a DNA restriction enzyme map for a region that best matches a shorter 'probe' map. Our algorithms utilize a new model of map alignments, and extensive experiments prove our model superior to earlier approaches for certain applications. Let M be the number of map sites and P be the number of probe sites. Our first algorithm, which optimizes only over a restricted class of alignments, requires O(MP log P) worst-case time and O(M + P) space. Our second algorithm, which optimizes over all alignments, runs in O(MP3) time and O(M + P2) space, under reasonable assumptions about the distribution of restriction enzyme cleavage sites. Combining the algorithms gives a map-searching method that optimizes over all alignments in O(MP log P) time in practice. The algorithms' effectiveness is illustrated by searches involving a genomic restriction map of Escherichia coli.

Algorithms↗
PubMed1991

Risk factors for acute graft-versus-host disease in histocompatible donor bone marrow transplantation.

We have analyzed factors associated with acute graft-versus-host disease following allogeneic bone marrow transplantation in 469 patients with histocompatible sibling donors between 1979 and 1987. Overall, 46 +/- 5% (95% confidence interval) developed clinical grade II-IV acute GVHD following transplantation. In univariate analysis, patient or donor age greater than or equal to 18 years was significantly associated with increased GVHD risks (greater than or equal to 18, 63 +/- 6% grade II-IV GVHD vs. less than 18, 27 +/- 6%, P less than .0001), without incremental risk in older adults. Univariate analysis showed that donor:recipient sex match and female:female transplants were associated with less-frequent GVHD. More frequent GVHD was associated with chronic myelogenous leukemia, cytomegalovirus seropositivity, and prior donor alloimmunity (pregnancy or transfusion). Additionally, the allele HLA-A26 was associated with increased risk of GVHD (72%, P = .005) while HLA-DR3 was associated with less GVHD (31%, P = .03). Stepwise multivariate analysis confirmed the increased GVHD risks associated with older recipient age, HLA-A26 and donor:recipient gender (not female:female) and the protective effect of HLA-DR3. Similar results were found using the different analytic technique of recursive partition analysis, which identified within the adult population the lowest GVHD risk in female recipients with nonalloimmunized female donors (20%), while other gender combinations had 68% acute GVHD, regardless of donor alloimmunity. In children (less than 18 years), lower GVHD risk accompanied donor:recipient sex-matched (18%) versus mismatched (33%) BMT. Clinical trials undertaken to lessen the hazards of GVHD must be designed with appropriate attention to these reproducibly identified clinical variables associated with different GVHD risks.

Age Factors↗
PubMed1991

Structured clinical teaching strategy.

This study investigated the impact of a structured exercise on low back pain, as part of a second year ambulatory course, on students' low back pain examination skills. One-hundred and eighty-eight medical students participated in one of four types of instructional intervention: 1) structured clinical exercise and reading, 2) random clinical experience and no reading, 3) reading only, and 4) no clinical experience or reading. At the end of the year, students completed an Objective Structured Clinical Exam (OSCE) in which two stations assessed back pain history and physical exam skills. An analysis of variance of the OSCE scores showed no significant difference in students' performance in relation to the type of instructional intervention. The General Professional Education of the Physician Report argues for the importance of structured clinical education. In medical education, unpredictable patient exposure and crowded curricula frequently result in students having none or only one structured learning opportunity to acquire critical skills. Unfortunately, this study found that assuring at least one structured clinical experience for a specific common problem seen in ambulatory care did not enhance student ability to select and use specific history or physical exam skills for that problem as assessed by an OSCE, as compared with students who did not have this experience. To assure that essential clinical skills are acquired, it most likely requires that both systematic instructional strategies and repeated learning opportunities are available to reinforce learning.

Ambulatory Care↗
PubMed1991

Electrosurgery thermal injury. Myth or misconception?

Two sets of experiments were conducted to determine whether the potential hazards of secondary sparking and distal tissue burns are a serious risk for surgeons using monopolar electrosurgery during laparoscopy. The results indicate that secondary sparking poses little threat, whereas distal burns are very likely, given certain tissue parameters that force the entire electric current through narrow structures.

Animals↗
PubMed1991

The activity of locally applied cytotoxics to breast cancer cells in vitro.

The ability of commonly used operative lavage solutions to destroy breast cancer cells was investigated. The cytotoxicity of solutions of Savlon, noxythiolin, povidone iodine, hydrogen peroxide, bleomycin and water on two human breast cancer cell lines was measured in vitro. Viable cells were determined by ability to exclude trypan blue. Results have been analysed with standard non-parametric tests and demonstrate that all solutions tested significantly (P less than 0.01) reduced the number of viable cells recovered when compared with a control solution of phosphate buffered saline. Solutions of Savlon, 2.5% noxythiolin and povidone iodine were more effective than the other agents in reducing the number of recovered viable cells.

Anti-Infective Agents, Local↗
PubMed1990

Basic local alignment search tool.

A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score. Recent mathematical results on the stochastic properties of MSP scores allow an analysis of the performance of this method as well as the statistical significance of alignments it generates. The basic algorithm is simple and robust; it can be implemented in a number of ways and applied in a variety of contexts including straightforward DNA and protein sequence database searches, motif searches, gene identification searches, and in the analysis of multiple regions of similarity in long DNA sequences. In addition to its flexibility and tractability to mathematical analysis, BLAST is an order of magnitude faster than existing sequence comparison tools of comparable sensitivity.

Algorithms↗