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PubMed2002

Mutation of macrophage colony stimulating factor (Csf1) causes osteopetrosis in the tl rat.

Osteopetrosis results from a heterogeneous group of congenital bone diseases that display inadequate osteoclastic bone resorption. We recently mapped tl (toothless), a mutation that causes osteopetrosis in rats, to a genetic region predicted to include the rat Csf1 gene. In this study, we sequenced the coding sequence of the rat Csf1 gene to determine if a mutation in Csf1 could be responsible for the tl phenotype. Sequencing revealed a 10-base insertion in the coding sequence of mutant animals that produces a frameshift and generates a stop codon early in the mutant Csf1 coding sequence. The 41 amino acid polypeptide predicted to be produced from the Csf1 promoter would have only the first nine amino acids of the wild-type rat protein. These data suggest that osteopetrosis develops in tl/tl rats because they cannot produce functional mCsf, a growth factor required for osteoclast differentiation and activation.

Amino Acid Sequence↗
PubMed2001

Assessment of prediction accuracy of protein function from protein--protein interaction data.

Functional prediction of open reading frames coded in the genome is one of the most important tasks in yeast genomics. Among a number of large-scale experiments for assigning certain functional classes to proteins, experiments determining protein-protein interaction are especially important because interacting proteins usually have the same function. Thus, it seems possible to predict the function of a protein when the function of its interacting partner is known. However, in vitro experiments often suffer from artifacts and a protein can often have multiple binding partners with different functions. We developed an objective prediction method that can systematically include the information of indirect interaction. Our method can predict the subcellular localization, the cellular role and the biochemical function of yeast proteins with accuracies of 72.7%, 63.6% and 52.7%, respectively. The prediction accuracy rises for proteins with more than three binding partners and thus we present the open prediction results for 16 such proteins.

Fungal Proteins↗
PubMed2001

Genes of Mycobacterium tuberculosis H37Rv downregulated in the attenuated strain H37Ra are restricted to M. tuberculosis complex species.

By comparing gene expression of virulent Mycobacterium tuberculosis H37Rv and attenuated strain H37Ra, we previously detected six genes that appear to be markedly downregulated in the attenuated strain compared with the virulent one. Three of these genes, i.e. Rv1345, Rv2770c, and Rv0288, code for proteins that can be predictively associated to immunological or pathogenetic aspects of M. tuberculosis infection; the other genes, i.e. Rv2336, Rv1320c, and Rv2819c, code for proteins with unknown functions (Rindi et al., 1999). In this paper we searched for the above mentioned genes in Pvu II-digested genomic DNA of a number of mycobacterial species by southern blot analysis employing PCR-generated probes in high-stringency conditions. Hybridization signals were only found in species belonging to the M. tuberculosis complex, i.e., M. tuberculosis, M. bovis, including the BCG strain, and M. microti, but not in other mycobacterial species, including M. avium, M. intracellulare, M. malmoense, M. xenopi, M. kansasii, M. simiae, M. marinum, M. scrofulaceum, M. gordonae, M. fortuitum, and M. smegmantis. These results indicate that genes Rv1345, Rv2770c, Rv0288, Rv2336, Rv1320c, and Rv2819c are associated with the most virulent mycobacteria and further support their potential role in M. tuberculosis virulence.

Blotting, Southern↗
PubMed1998

Analysis of complement receptor type 1 (CR1) expression on erythrocytes and of CR1 allelic markers in Caucasian and African American populations.

CR1 expression on erythrocytes (E) is regulated by an element that is tightly linked in Caucasians to the site of an RFLP of the CR1 gene. Genomic HindIII fragments of 7.4 and 6.9 kb identify alleles that are expressed in high (H allele) or low (L allele) amounts, respectively. When age-fractionated E of donors heterozygous for both the H and L alleles and for CR1 allotypes of differing molecular weights were analyzed in Western blots, the product of the L allele appeared to have an increased rate of loss during cell aging. A coding sequence polymorphism of CR1 predicted to cause a Pro-->Arg substitution in its proximal extramembranous region was tightly linked in Caucasians to the site of the HindIII RFLP. However, neither this polymorphism nor the HindIII RFLP correlated with CR1 expression among African Americans. Relative instability of CR1 encoded by the L allele thus may derive from another coding sequence polymorphism, or may require both the Pro-->Arg substitution and epistatic effects of another polymorphic gene.

Alleles↗
PubMed2006

Wavelet-based scalable L-infinity-oriented compression.

Among the different classes of coding techniques proposed in literature, predictive schemes have proven their outstanding performance in near-lossless compression. However, these schemes are incapable of providing embedded L(infinity)-oriented compression, or, at most, provide a very limited number of potential L(infinity) bit-stream truncation points. We propose a new multidimensional wavelet-based L(infinity)-constrained scalable coding framework that generates a fully embedded L(infinity)-oriented bit stream and that retains the coding performance and all the scalability options of state-of-the-art L2-oriented wavelet codecs. Moreover, our codec instantiation of the proposed framework clearly outperforms JPEG2000 in L(infinity) coding sense.

Algorithms↗
PubMedDate not supplied

Ability of the D-15 panel tests and HRR pseudoisochromatic plates to predict performance in naming VDT colors.

Color codes in VDT displays often contain sets of colors that are confusing to individuals with color-vision deficiencies. The purpose of this study is to determine whether individuals with color-vision deficiencies (color defectives) can perform as well as individuals without color-vision deficiencies (color normals) on a colored VDT display used in the railway industry and to determine whether clinical color-vision tests can predict their performance. Of the 52 color defectives, 58% failed the VDT test. The kappa coefficients of agreement for the Farnsworth D-15, Adams desaturated D-15, and Richmond 3rd Edition HRR PIC diagnostic plates were significantly greater than chance. In particular, the D-15 tests have a high probability of predicting who fails the practical test. However, all three tests had an unacceptably high false-negative rate (9.5-35%); so that a practical test is still needed.

Color Perception↗
PubMed1999

Risk adjustment for complications of hysterectomy: limitations of routinely collected administrative data.

OBJECTIVE: We sought to determine the utility of routinely collected administrative data for risk adjustment for complications of hysterectomy. STUDY DESIGN: Using abstracted discharge data on 107, 648 women undergoing hysterectomy in North Carolina from 1988 through 1994, we constructed logistic regression models for the prediction of medical and surgical complications incorporating coded demographic, diagnostic, and procedural data. RESULTS: The overall complication rate was 16%, with surgical complications (11.8%) more common than medical complications (6.7%). Hysterectomy type, teaching hospital status, patient age >/=65 years, and insurance status of Medicaid or no insurance were significantly associated with both medical and surgical complication risk, as were procedures performed for cancer or pregnancy complications. Models that incorporated coded comorbidity were better predictors of medical complications (C = 0.714) than surgical complications (C = 0.630). CONCLUSION: Although surgical complications of hysterectomy are more common than medical complications, risk adjustment methods that use routinely collected administrative data are better at predicting medical complications. Ambiguities in coding, misclassification, and uncoded factors such as disease severity limit the utility of administrative data for risk adjustment for hysterectomy complications.

Adult↗
PubMed2005

[Comparison study on the methods for finding borders between coding and non-coding DNA regions in rice].

Entropy-based divergence measures have provided an impelling tool in evaluating sequence complexity, predicting CpG island, and detecting borders between coding and non-coding DNA regions etc. In this paper, two new divergence measures: the alpha-KL divergence and the alpha-Jensen-Shannon divergence were defined and a coarse-graining vector of amino acids- corresponding codons was proposed according to codons GC-content, in order to improve the computational approach to finding borders between coding and non-coding in rice. A comparison of the accuracies gained by different vectors (the Jensen-Shannon divergence, the Jensen-Renyi divergence, the alpha-KL divergence and the alpha-Jensen -Shannon divergence) showed that recognition efficiency based on the new information measures with the vector coarse-graining increase by 4-5 times than that of Bernaola's method in the 'stop codon' of coding regions in rice.

Algorithms↗
PubMed2002

The KEGG databases at GenomeNet.

The Kyoto Encyclopedia of Genes and Genomes (KEGG) is the primary database resource of the Japanese GenomeNet service (http://www.genome.ad.jp/) for understanding higher order functional meanings and utilities of the cell or the organism from its genome information. KEGG consists of the PATHWAY database for the computerized knowledge on molecular interaction networks such as pathways and complexes, the GENES database for the information about genes and proteins generated by genome sequencing projects, and the LIGAND database for the information about chemical compounds and chemical reactions that are relevant to cellular processes. In addition to these three main databases, limited amounts of experimental data for microarray gene expression profiles and yeast two-hybrid systems are stored in the EXPRESSION and BRITE databases, respectively. Furthermore, a new database, named SSDB, is available for exploring the universe of all protein coding genes in the complete genomes and for identifying functional links and ortholog groups. The data objects in the KEGG databases are all represented as graphs and various computational methods are developed to detect graph features that can be related to biological functions. For example, the correlated clusters are graph similarities which can be used to predict a set of genes coding for a pathway or a complex, as summarized in the ortholog group tables, and the cliques in the SSDB graph are used to annotate genes. The KEGG databases are updated daily and made freely available (http://www.genome.ad.jp/kegg/).

Animals↗
PubMed1998

Proper coding and billing for office services.

The information revolution has effected tumultuous change in the process by which physicians receive compensation for their services. In an effort to predict and control costs, a labyrinthine coding system, together with multilayered rules and regulations, has been developed to pinpoint medical function. Computerization of the insurance industry allows vigilant scrutiny of the physicians claims. Since noncompliance with payment rules now carries legal or monetary consequences, physicians need to pay careful attention to payer methodology, not only to fulfill the requirements of the law but also to receive accurate and optimal reimbursement. This article is designed to help practitioners unscramble these exacting mandates and stay in alignment.

Fees and Charges↗
PubMed2001

Screening for high utilizing somatizing patients using a prediction rule derived from the management information system of an HMO: a preliminary study.

BACKGROUND: Somatization is a common, costly problem with great morbidity, but there has been no effective screening method to identify these patients and target them for treatment. OBJECTIVES: We tested a hypothesis that we could identify high utilizing somatizing patients from a management information system (MIS) by total number of visits and what we termed "somatization potential," the percentage of visits for which ICD-9 primary diagnosis codes represented disorders in the musculoskeletal, nervous, or gastrointestinal systems or ill-defined complaints. METHODS: We identified 883 high users from the MIS of a large staff model HMO as those having six or more visits during the year studied (65th percentile). A physician rater, without knowledge of hypotheses and predictors, then reviewed the medical records of these patients and identified somatizing patients (n = 122) and nonsomatizing patients (n = 761). In two-thirds of the population (the derivation set), we used logistic regression to refine our hypothesis and identify predictors of somatization available from the MIS: demographic data, all medical encounters, and primary diagnoses made by usual care physicians (ICD-9 codes). We then tested our prediction model in the remaining one-third of the population (the validation set) to validate its usefulness. RESULTS: The derivation set contained the following significant correlates of somatization: gender, total number of visits, and percent of visits with somatization potential. The c-statistic, equivalent to the area under the ROC curve, was 0.90. In the validation set, the explanatory power was less with a still impressive c-statistic of 0.78. A predicted probability of 0.04 identified almost all somatizers, whereas a predicted probability of 0.40 identified about half of all somatizers but produced few false positives. CONCLUSIONS: We have developed and validated a prediction model from the MIS that helps to distinguish chronic somatizing patients from other high utilizing patients. Our method requires corroboration but carries the promise of providing clinicians and health plan directors with an inexpensive, simple approach for identifying the common somatizing patient and, in turn, targeting them for treatment. The screener does not require clinicians' time.

Adult↗
PubMed1996

Molecular characterization of antigenic polymorphisms (Ond(a) and Mart(a)) of the beta 2 family recognized by human leukocyte alloantisera.

We show that the previously described alloantisera Ond and Mart, which recognize the alloantigens Ond(a) and Mart(a), react with polymorphic variants of alpha L and alpha M subunits of the beta 2 integrin family (CD11a and CD11b molecules). This was shown by testing the alloantisera in a monoclonal antibody-specific immobilization of leukocyte antigens, immunoprecipitation, and immunofluorescence assay against cells from normal donors and from patients with leukocyte adhesion deficiency (beta 2 intergrin deficient). To elucidate the molecular basis of the Ond(a) and Mart(a) alloantigens, RNA was isolated from mononuclear leukocytes derived from individuals of known serologic phenotype. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to amplify the entire coding region of the alpha L and alpha M mRNAs. The Ond(a) antigen was found to be due to a G2466C substitution in the DNA coding for the alpha L subunit, which predicts an Arg766Thr amino-acid polymorphism. The Mart(a) antigen was also found to be due to a single nucleotide substitution (G302A) in the DNA coding for the alpha M subunit, which predicts an Arg61His amino acid polymorphism. Using allele-specific restriction enzyme analysis, the association between point mutations and phenotypes was confirmed. The localization of these alloantigens on integrin molecules further illustrates the polymorphic nature of this class of proteins. Whether the polymorphisms influence the adhesive capacity of the leukocyte integrins remains to be investigated.

Alleles↗
PubMed2001

Accuracy of velocity estimation by Reichardt correlators.

Although a great deal of experimental evidence supports the notion of a Reichardt correlator as a mechanism for biological motion detection, the correlator does not signal true image velocity. This study examines the accuracy with which realistic Reichardt correlators can provide velocity estimates in an organism's natural visual environment. The predictable statistics of natural images imply a consistent correspondence between mean correlator response and velocity, allowing the otherwise ambiguous Reichardt correlator to act as a practical velocity estimator. Analysis and simulations suggest that processes commonly found in visual systems, such as prefiltering, response compression, integration, and adaptation, improve the reliability of velocity estimation and expand the range of velocities coded. Experimental recordings confirm our predictions of correlator response to broadband images.

Animals↗
PubMed1992

Accuracy of asthma statistics from death certificates in South Australia.

OBJECTIVE: To assess the accuracy of asthma statistics from death certificates in South Australia. DESIGN: Comparison of death certificate coding with expert panel assessments of causes of death after interviews with certifying doctors, regular medical practitioners and close acquaintances of the deceased. SUBJECTS: 261 subjects for whom the term "asthma", "asthmatic" or "asthmaticus" was recorded in Part I or Part II of death certificates lodged in the 24-month period from May 1988. MAIN OUTCOME MEASURES: Sensitivity, specificity and predictive value of death certificate coding, with expert panel assessments as the reference standard. RESULTS: About 95% of deaths assessed as definitely due to asthma were so coded from death certificates, but only 69% of deaths assessed by the panel as not due to asthma were coded to a "non-asthmatic" cause. Of the 129 deaths coded to asthma, the percentage assessed as definitely or likely to be due to asthma was 56%. For ages under 65 years, this figure was 84% compared with only 38% for older subjects. CONCLUSION: The accuracy of death certificate data on asthma for the age group 65 years and over would be too low at present for most epidemiological purposes.

Abstracting and Indexing↗
PubMed1987

Cognitive maps as orienting schemata.

A "point-to-unseen-targets" task was used to test two theories about the nature of cognitive mapping. The hypothesis that a cognitive map is like a "picture in the head" predicts that (a) the cognitive map should have a preferred orientation and (b) all coded locations should be equally available. These predictions were confirmed in Experiments 1 and 3 when targets were cities in the northeastern United States and learning was from a map. The theory that a cognitive map is an orienting schema predicts that the cognitive map should have no preferred orientation and that targets in front of the body should be localized faster than targets behind the body. These predictions were confirmed in Experiments 1 and 2 when targets were local landmarks that had been learned via direct experience. In Experiment 3, when cities in the Northeast were targets and geographical knowledge had been acquired, in part, by traveling in the Northeast, the observed latency profiles were not as predicted by either theory of cognitive mapping. The results suggest that orienting schemata direct orientation with respect to local environments, but that orientation with respect to large geographical regions is supported by a different type of cognitive structure.

Attention↗
PubMed1986

The amino-terminal domain of the v-fms oncogene product includes a functional signal peptide that directs synthesis of a transforming glycoprotein in the absence of feline leukemia virus gag sequences.

The nucleotide sequence of a 5' segment of the human genomic c-fms proto-oncogene suggested that recombination between feline leukemia virus and feline c-fms sequences might have occurred in a region encoding the 5' untranslated portion of c-fms mRNA. The polyprotein precursor gP180gag-fms encoded by the McDonough strain of feline sarcoma virus was therefore predicted to contain 34 v-fms-coded amino acids derived from sequences of the c-fms gene that are not ordinarily translated from the proto-oncogene mRNA. The (gP180gag-fms) polyprotein was cotranslationally cleaved near the gag-fms junction to remove its gag gene-coded portion. Determination of the amino-terminal sequence of the resulting v-fms-coded glycoprotein, gp120v-fms, showed that the site of proteolysis corresponded to a predicted signal peptidase cleavage site within the c-fms gene product. Together, these analyses suggested that the linked gag sequences may not be necessary for expression of a biologically active v-fms gene product. The gag-fms sequences of feline sarcoma virus strain McDonough and the v-fms sequences alone were inserted into a murine retroviral vector containing a neomycin resistance gene. Both constructs were biologically active when transfected into NIH 3T3 cells and produced morphologically transformed foci at equivalent efficiencies. When transfected into a cell line (psi 2) expressing complementary viral gene functions, G418-resistant (Neor) cells containing either of these vector DNAs produced high titers of transforming viruses. Analysis of proteins produced in cells containing the vector lacking gag gene sequences showed that gP180gag-fms was not synthesized, whereas normal levels of both immature gp120v-fms and mature gp140v-fms were detected. The glycoprotein was efficiently transported to the cell surface, and it retained wild-type tyrosine kinase activity. We conclude that a cryptic hydrophobic signal peptide sequence in v-fms was unmasked by gag deletion, thereby allowing the correct orientation and transport of the v-fms gene product within membranous organelles. It seems likely that the proteolytic cleavage of gP180gag-fms is mediated by signal peptidase and that the amino termini of gp140v-fms and the c-fms gene product are identical.

Amino Acid Sequence↗
PubMed1985

A transcription termination signal immediately precedes the coding sequence for the chloramphenicol-inducible plasmid gene cat-86.

The plasmid gene cat-86 specifies chloramphenicol-inducible, chloramphenicol acetyltransferase in Bacillus subtilis. The inducible regulation is independent of the promoter that is used to activate cat-86 and is independent of the cat-86 coding sequence. We have proposed that the regulation of cat-86 results from the transcription of a pair of inverted-repeat sequences that immediately precede the coding sequence. These transcripts are predicted to sequester the cat-86 ribosome binding site in a stable RNA stem-loop which, in theory, should block the ribosome binding site from pairing with 16S rRNA. Inducible expression of cat-86 may therefore result in part from regulation of the translation of cat-86 mRNA. However, chloramphenicol-induction correlates with increased levels of cat-86 mRNA and the RNA stem-loop preceding the cat-86 coding sequence structurally resembles a rho-independent transcription terminator. We have therefore tested the inverted-repeats as a potential site of transcription termination. Transcription studies performed in vitro using SP6 RNA polymerase and in vivo by S1 mapping demonstrate that a substantial fraction of the potential cat-86 transcripts terminate at a site immediately 3' to the inverted-repeats. The results of the in vivo experiments suggest that the termination signal may be partially relieved by growth of cells in chloramphenicol.

Acetyltransferases↗
PubMed1991

Molecular cloning of matrin F/G: A DNA binding protein of the nuclear matrix that contains putative zinc finger motifs.

We have isolated a 2.7-kilobase rat liver cDNA clone that contains the entire 544-amino acid coding sequence for matrin F/G. This protein has previously been localized to the internal, fibrogranular areas of the nuclear matrix and shown to bind to DNA on nitrocellulose blots. The predicted amino acid sequence from the coding region of this cDNA shows that this protein contains approximately 50% hydrophobic amino acids with secondary structure predictions suggesting a large percentage of beta-sheet regions. No significant homologies were found with any other known proteins, including the nuclear lamins. The predicted amino acid sequence was also searched for DNA binding motifs. Two putative zinc finger motifs were found. In addition, a 7-mer palindromic sequence (Ser-Ser-Thr-Asn-Thr-Ser-Ser) was discovered within one of these zinc finger DNA binding regions. A possible regulatory role for this element is discussed.

Amino Acid Sequence↗